1 00:00:05,040 --> 00:00:06,441 FOR THOSE WATCHING ON THE VIDEO 2 00:00:06,441 --> 00:00:07,943 CAST I'D LIKE TO SHARE WITH YOU 3 00:00:07,943 --> 00:00:11,513 THIS VIDEOCAST IS RECORDED AND 4 00:00:11,513 --> 00:00:14,716 ARCHIVED FOR FUTURE VIEWING. 5 00:00:14,716 --> 00:00:18,887 YOU SEE THE SAME LINK SO WE'LL 6 00:00:18,887 --> 00:00:19,655 BEGIN WITH OUR WELCOME 7 00:00:19,655 --> 00:00:28,530 REMARKS -- FROM DR. LANGEVIN FOR 8 00:00:28,530 --> 00:00:30,265 THE CENTER FROM COMPLEMENTARY 9 00:00:30,265 --> 00:00:32,234 AND INTEGRATED HEALTH. 10 00:00:32,234 --> 00:00:36,438 PREVIOUSLY SHE WAS THE DIRECTOR 11 00:00:36,438 --> 00:00:39,274 OF THE CENTER FOR INTEGRATED 12 00:00:39,274 --> 00:00:41,343 MEDICINE AND PROFESSOR OF 13 00:00:41,343 --> 00:00:44,179 MEDICINE AT BRIGHAM WOMEN'S 14 00:00:44,179 --> 00:00:45,881 HOSPITAL AND HARVARD MEDICAL 15 00:00:45,881 --> 00:00:46,148 SCHOOL. 16 00:00:46,148 --> 00:00:48,116 SHE HAS BEEN WELL KNOWN FOR HER 17 00:00:48,116 --> 00:00:49,751 VISIONARY LEADERSHIP AND TODAY 18 00:00:49,751 --> 00:00:51,920 SHE WILL SHARE WITH US HER 19 00:00:51,920 --> 00:00:53,055 VISION OF HOW INTEROCEPTION 20 00:00:53,055 --> 00:01:01,363 RESEARCH IS ALIGNED WITH NCCIH'S 21 00:01:01,363 --> 00:01:03,799 PRIORITY. 22 00:01:03,799 --> 00:01:12,241 DR. LANGEVIN PLEASE SHARE YOUR 23 00:01:12,241 --> 00:01:13,342 SCREEN. 24 00:01:13,342 --> 00:01:15,611 >> ALL RIGHT. 25 00:01:15,611 --> 00:01:15,811 GOOD. 26 00:01:15,811 --> 00:01:20,215 YOU CAN ALL SEE THIS I HOPE? 27 00:01:20,215 --> 00:01:23,418 IT IS MY GREAT PLEASURE TO OPEN 28 00:01:23,418 --> 00:01:25,587 THE SECOND ANNUAL NIH 29 00:01:25,587 --> 00:01:26,855 INVESTIGATOR MEETING ON 30 00:01:26,855 --> 00:01:27,456 INTEROCEPTION RESEARCH. 31 00:01:27,456 --> 00:01:28,857 THROUGHOUT THE HISTORY OF 32 00:01:28,857 --> 00:01:31,260 MEDICINE WE HAVE HAD A STRONG 33 00:01:31,260 --> 00:01:33,095 TENDENCY TO THINK ABOUT THE BODY 34 00:01:33,095 --> 00:01:36,498 ONE ORGAN OR SYSTEM AT A TIME. 35 00:01:36,498 --> 00:01:38,934 BUT ONCE IN A WHILE WE ARE 36 00:01:38,934 --> 00:01:40,702 PRESENTED WITH AN OPPORTUNITY TO 37 00:01:40,702 --> 00:01:42,337 INCREASE OUR UNDERSTANDING OF 38 00:01:42,337 --> 00:01:44,339 THE WHOLE. 39 00:01:44,339 --> 00:01:45,908 AND THIS MEETING ON 40 00:01:45,908 --> 00:01:47,042 INTEROCEPTION IS ONE OF THEM. 41 00:01:47,042 --> 00:01:50,445 WHAT DO I MEAN BY THAT? 42 00:01:50,445 --> 00:01:51,580 WELL, WE'LL LONG KNOWN THERE ARE 43 00:01:51,580 --> 00:01:54,750 SYSTEMS IN THE BODY BY NATURE 44 00:01:54,750 --> 00:01:56,985 INTEGRATIVE BE IT THE ENDOCRINE 45 00:01:56,985 --> 00:01:57,886 SYSTEM FOR EXAMPLE INTERACTS 46 00:01:57,886 --> 00:01:59,988 WITH ALL THE ORGANS AND THE 47 00:01:59,988 --> 00:02:02,724 IMMUNE SYSTEM AND WE'RE ALSO 48 00:02:02,724 --> 00:02:06,094 BEGINNING TO THINK EVEN OF THE 49 00:02:06,094 --> 00:02:07,229 MICROBIOME OF BEING ANOTHER 50 00:02:07,229 --> 00:02:08,630 CROSS-CUTTING SYSTEM. 51 00:02:08,630 --> 00:02:12,668 AND WE HAVE KNOWN FOR OVER A 52 00:02:12,668 --> 00:02:15,938 CENTURY THE AUTONOMIC SERVICE 53 00:02:15,938 --> 00:02:19,641 REGULATE THE ORGANS AND SYSTEMS 54 00:02:19,641 --> 00:02:25,714 AND IT WAS RECENTLY WE BEGAN TO 55 00:02:25,714 --> 00:02:26,581 APPRECIATE THE LANDSCAPE OF THE 56 00:02:26,581 --> 00:02:28,850 TWO-WAY CONVERSATION BETWEEN OUR 57 00:02:28,850 --> 00:02:32,120 BRAIN AND OUR INTERNAL ORGANS. 58 00:02:32,120 --> 00:02:35,157 AND THIS CONNECTION INVOLVES OF 59 00:02:35,157 --> 00:02:39,261 COURSE THE AUTONOMIC NORM SYSTEM 60 00:02:39,261 --> 00:02:42,064 AND THE INNERVATING DEEP TISSUES 61 00:02:42,064 --> 00:02:44,433 WE'RE JUST BEGINNING TO 62 00:02:44,433 --> 00:02:47,769 APPRECIATE. 63 00:02:47,769 --> 00:02:48,870 BROADLY SPEAKING, INTEROCEPTION 64 00:02:48,870 --> 00:02:50,906 REFERS TO OUR ABILITY TO SENSE 65 00:02:50,906 --> 00:02:52,574 AND RESPOND TO SIGNALS GENERATED 66 00:02:52,574 --> 00:02:55,577 FROM OUR INTERNAL WORLD OPPOSED 67 00:02:55,577 --> 00:02:58,981 TO EXTERNAL SIGNALS SUCH AS 68 00:02:58,981 --> 00:02:59,781 SOUND, FOR EXAMPLE OR FEELING ON 69 00:02:59,781 --> 00:03:00,849 THE SKIN. 70 00:03:00,849 --> 00:03:03,752 HOW AWARE OR HOW UNAWARE WE ARE 71 00:03:03,752 --> 00:03:06,989 OF THESE SENSATIONS AND AS 72 00:03:06,989 --> 00:03:08,323 CONVERSATION BETWEEN BRAIN AND 73 00:03:08,323 --> 00:03:12,427 INSIDE OF OUR BODY IS A 74 00:03:12,427 --> 00:03:16,231 FASCINATING TOPIC WHICH WE 75 00:03:16,231 --> 00:03:16,465 LAUNCH. 76 00:03:16,465 --> 00:03:23,038 THIS TOPIC GOES TREATMENT AND 77 00:03:23,038 --> 00:03:33,448 PRACTICES THAT TAP INTO 78 00:03:36,485 --> 00:03:38,220 MEDICATION AND YOGA AND THIS 79 00:03:38,220 --> 00:03:40,689 EXCITING MEETING WILL GIVES A 80 00:03:40,689 --> 00:03:43,959 CHANCE TO HEAR FROM 81 00:03:43,959 --> 00:03:44,960 INVESTIGATORS EXPLORING 82 00:03:44,960 --> 00:03:47,229 FUNDAMENTAL INTEROCEPTIVE 83 00:03:47,229 --> 00:03:48,530 MECHANISMS THAT PROVIDE MUCH 84 00:03:48,530 --> 00:03:49,798 NEEDED BASIC UNDERSTANDING OF 85 00:03:49,798 --> 00:03:54,069 THE CONNECTIONS BETWEEN OUR 86 00:03:54,069 --> 00:03:55,904 NERVOUS SYSTEM AND THE REST OF 87 00:03:55,904 --> 00:03:56,304 THE BODY. 88 00:03:56,304 --> 00:03:57,539 THESE CONCESSIONS ARE ESSENTIAL 89 00:03:57,539 --> 00:03:59,875 FOR US TO ARRIVE AT AN 90 00:03:59,875 --> 00:04:01,209 INFORMATION OF OUR BODY AS A 91 00:04:01,209 --> 00:04:04,179 WHOLE AND HEALTH IN GENERAL. 92 00:04:04,179 --> 00:04:05,981 UNLIKE DISEASE THAT MANIFESTS IN 93 00:04:05,981 --> 00:04:08,016 SPECIFIC ORGANS OR SYSTEMS, 94 00:04:08,016 --> 00:04:09,117 HEALTH INVOLVES THE WHOLE 95 00:04:09,117 --> 00:04:10,552 PERSON. 96 00:04:10,552 --> 00:04:15,791 AND SO INTEGRATIVE PROCESSES 97 00:04:15,791 --> 00:04:21,096 SUCH AS INTEROCEPTION INTEGRATED 98 00:04:21,096 --> 00:04:22,931 NOT JUST ACROSS ORGANS AND 99 00:04:22,931 --> 00:04:27,035 SYSTEMS BUT SCALES, CELLULAR AND 100 00:04:27,035 --> 00:04:31,440 MOLECULAR MECHANISMS TO WHOLE 101 00:04:31,440 --> 00:04:34,776 ORGAN PHYSIOLOGY SUCH AS EATING 102 00:04:34,776 --> 00:04:36,545 AND DRINKING FUNDAMENTAL TO 103 00:04:36,545 --> 00:04:36,778 HEALTH. 104 00:04:36,778 --> 00:04:38,814 WE'RE ALL LOOKING FORWARD 105 00:04:38,814 --> 00:04:39,281 EXCITING MEETING. 106 00:04:39,281 --> 00:04:40,949 WE'RE PLEASED SO MANY OF YOU 107 00:04:40,949 --> 00:04:42,818 WERE ABLE TO BE HERE WITH ONE 108 00:04:42,818 --> 00:04:43,852 ANOTHER IN PERSON AND I JUST 109 00:04:43,852 --> 00:04:48,457 WISH I COULD BE THERE WITH YOU 110 00:04:48,457 --> 00:04:48,990 AND WISH YOU ALL A GREAT 111 00:04:48,990 --> 00:04:59,134 MEETING. 112 00:05:00,068 --> 00:05:02,037 >> THANK YOU SO MUCH FOR THE 113 00:05:02,037 --> 00:05:04,039 WONDERFULLY INSIGHTFUL COMMENTS, 114 00:05:04,039 --> 00:05:05,140 DR. LANGEVIN. 115 00:05:05,140 --> 00:05:11,880 WE NOW ARE GOING TO WELCOME 116 00:05:11,880 --> 00:05:18,720 DR. WALLER KOROSHETZ DIRECTOR OF 117 00:05:18,720 --> 00:05:28,463 THE NATIONAL INSTITUTE OF NINDS. 118 00:05:28,463 --> 00:05:29,131 DLIFSHTH NATIONAL INSTITUTE OF 119 00:05:29,131 --> 00:05:31,600 NEUROLOGICAL DISORDERS AND 120 00:05:31,600 --> 00:05:32,033 STROKE. 121 00:05:32,033 --> 00:05:34,870 DR. KOROSHETZ HAS BEEN THE NINDS 122 00:05:34,870 --> 00:05:37,873 DIRECTOR SINCE 2014 AND WAS 123 00:05:37,873 --> 00:05:41,276 DEPUTY DIRECTOR BETWEEN 2007 AND 124 00:05:41,276 --> 00:05:42,244 2014. 125 00:05:42,244 --> 00:05:43,478 PRIOR TO JOINING NINDS, 126 00:05:43,478 --> 00:05:45,547 DR. KOROSHETZ WAS ALSO A 127 00:05:45,547 --> 00:05:48,250 PROFESSOR OF NEUROLOGY AT 128 00:05:48,250 --> 00:05:50,819 HARVARD MEDICAL SCHOOL AND 129 00:05:50,819 --> 00:05:52,821 SERVED AS VICE CHAIR OF THE 130 00:05:52,821 --> 00:05:55,190 NEUROLOGY SERVICE AND DIRECTOR 131 00:05:55,190 --> 00:05:57,759 OF STROKE AND NEURON INTENSIVE 132 00:05:57,759 --> 00:05:59,761 CARE AT MASSACHUSETTS GENERAL 133 00:05:59,761 --> 00:06:02,464 HOSPITAL FOR ALMOST TWO DECADES. 134 00:06:02,464 --> 00:06:05,100 DR. KOROSHETZ IS HIGHLY ADMIRED 135 00:06:05,100 --> 00:06:07,736 AND LOVED LEADER WITHIN THE NIH 136 00:06:07,736 --> 00:06:10,972 COMMUNITY AND HAS LED MAJOR 137 00:06:10,972 --> 00:06:13,308 TRANS-NIH INITIATIVES INCLUDING 138 00:06:13,308 --> 00:06:16,444 THE FAMOUS BRAIN INITIATIVE AND 139 00:06:16,444 --> 00:06:20,815 THE HEAL INITIATIVE AND THE NIH 140 00:06:20,815 --> 00:06:22,384 BLUEPRINT FOR NEUROSCIENCE 141 00:06:22,384 --> 00:06:22,651 RESEARCH. 142 00:06:22,651 --> 00:06:27,923 TODAY, HE IS REPRESENTING THE 143 00:06:27,923 --> 00:06:30,926 BLUEPRINT SENIOR LEADERSHIP TO 144 00:06:30,926 --> 00:06:31,893 SHARE WITH US ABOUT WHAT 145 00:06:31,893 --> 00:06:35,397 BLUEPRINT IS ALL ABOUT AND HOW 146 00:06:35,397 --> 00:06:38,600 IT HAS INITIATED AND SUPPORTED 147 00:06:38,600 --> 00:06:42,437 THE INTERO CEPTION RESEARCH AT 148 00:06:42,437 --> 00:06:42,671 THE NIH. 149 00:06:42,671 --> 00:06:52,914 DR. KOROSHETZ. 150 00:06:57,686 --> 00:07:00,488 >> GOOD MORNING? 151 00:07:00,488 --> 00:07:03,291 HOW'S EVERYONE FEELING? 152 00:07:03,291 --> 00:07:06,494 GOOD, YOUR INTEROCEPTION SYSTEM 153 00:07:06,494 --> 00:07:08,563 IS WORK. 154 00:07:08,563 --> 00:07:11,032 I'M HERE FOR THE BLUEPRINT. 155 00:07:11,032 --> 00:07:14,002 IT'S A GROUP OF INSTITUTES AT 156 00:07:14,002 --> 00:07:15,003 NIH THAT WORK TOGETHER IN 157 00:07:15,003 --> 00:07:16,304 VARIOUS DOMAINS. 158 00:07:16,304 --> 00:07:19,574 A LOT OF IT IS FOCUSSED ON 159 00:07:19,574 --> 00:07:23,511 FUNDING TRAINING, FUNDING TOOLS. 160 00:07:23,511 --> 00:07:31,219 WE WORKED ON THE MRI CONNECTOME 161 00:07:31,219 --> 00:07:34,289 PROJECT AND WORKED ON WHERE BIO 162 00:07:34,289 --> 00:07:37,759 TECH COMPANIES CAN COME IN AND 163 00:07:37,759 --> 00:07:38,827 WORK WITH A VIRTUAL 164 00:07:38,827 --> 00:07:39,928 PHARMACEUTICAL COMPANY SETUP TO 165 00:07:39,928 --> 00:07:43,732 DEVELOP THERAPIES AND WE HAVE 166 00:07:43,732 --> 00:07:46,534 PRETTY MUCH ALL THE NEUROSCIENCE 167 00:07:46,534 --> 00:07:49,237 INSTITUTES INVOLVED IN THE 168 00:07:49,237 --> 00:07:49,537 BLUEPRINT. 169 00:07:49,537 --> 00:07:52,774 SOME OF THE THINGS THAT I 170 00:07:52,774 --> 00:07:53,842 MENTIONED ARE THE 171 00:07:53,842 --> 00:07:56,344 NEUROTHERAPEUTICS NETWORK TO GET 172 00:07:56,344 --> 00:07:57,512 THERAPEUTICS OUT AND THIS 173 00:07:57,512 --> 00:07:58,647 SERVICES ALL THE DIFFERENT 174 00:07:58,647 --> 00:07:59,981 INSTITUTES. 175 00:07:59,981 --> 00:08:10,458 IT COULD BE ON THAT MOL -- 176 00:08:12,127 --> 00:08:13,862 BIOLOGICS AND WE HAVE DEVICE 177 00:08:13,862 --> 00:08:19,768 PROGRAMS ALSO TO MOVE THINGS TO 178 00:08:19,768 --> 00:08:21,703 COMMERCIALIZATION THESE ARE 179 00:08:21,703 --> 00:08:22,904 INTEGRATED WITH OTHER PROGRAMS 180 00:08:22,904 --> 00:08:28,076 AT NIH PARTICULARLY FOR THIS 181 00:08:28,076 --> 00:08:29,511 GROUP THE SPARK PROGRAM 182 00:08:29,511 --> 00:08:33,948 DEVELOPING MAPS AND WAYS OF 183 00:08:33,948 --> 00:08:37,552 MODULATING THE PERIPHERAL 184 00:08:37,552 --> 00:08:38,453 NERVOUS SYSTEM FOR HEALTH. 185 00:08:38,453 --> 00:08:41,656 HERE TO TALK ABOUT THE AMAZING 186 00:08:41,656 --> 00:08:46,861 SCIENCE DONE IN THIS SPACE 187 00:08:46,861 --> 00:08:48,363 CALLED INTEROCEPTION. 188 00:08:48,363 --> 00:08:53,168 AS HELLENE MENTIONED THIS IS 189 00:08:53,168 --> 00:08:54,536 UNDERSTANDING HOW OUR NERVOUS 190 00:08:54,536 --> 00:08:59,574 SYSTEM WHICH INNERVATED ALMOST 191 00:08:59,574 --> 00:09:02,344 ALL THE ASPECTS OF OUR BODY AND 192 00:09:02,344 --> 00:09:03,678 HOW OUR BRAIN CONTROLS IT AND 193 00:09:03,678 --> 00:09:06,014 HOW THE BRAIN GETS INPUTS FROM 194 00:09:06,014 --> 00:09:07,215 ALL THESE DIFFERENT AREAS AND 195 00:09:07,215 --> 00:09:10,518 HOW IT'S INTEGRATED INTO BRAIN 196 00:09:10,518 --> 00:09:12,620 FUNCTION WHETHER IT'S AUTOMATIC 197 00:09:12,620 --> 00:09:15,190 FUNCTION OR AS WE STARTED OFF 198 00:09:15,190 --> 00:09:18,560 HOW WE ACTUALLY FEEL TODAY AND 199 00:09:18,560 --> 00:09:20,028 WE'RE GETTING INPUTS ALL THE 200 00:09:20,028 --> 00:09:22,697 TIME WE DON'T PAY ATTENTION TO. 201 00:09:22,697 --> 00:09:25,834 THEY'RE PROBABLY DETERMINING A 202 00:09:25,834 --> 00:09:32,774 LOT OF OUR BEHAVIORS AND SO THIS 203 00:09:32,774 --> 00:09:43,318 SYSTEM AS HELENE MENTIONED THERE 204 00:09:43,518 --> 00:09:45,653 IS WORK THAT SEEMS TO INCUR IN 205 00:09:45,653 --> 00:09:49,124 ANIMALS IN THE '50s AND '60s AND 206 00:09:49,124 --> 00:09:51,159 MAYBE WAS LEFT IN THE DUST A 207 00:09:51,159 --> 00:09:51,459 LITTLE BIT. 208 00:09:51,459 --> 00:09:52,827 WE'RE TRYING TO RESURRECT IT AND 209 00:09:52,827 --> 00:09:55,130 LEARNING AMAZING THINGS. 210 00:09:55,130 --> 00:09:57,298 SOME THINGS YOU'LL HEAR ABOUT 211 00:09:57,298 --> 00:09:59,134 TODAY FROM THE INVESTIGATORS 212 00:09:59,134 --> 00:10:03,004 FUNDED OUT OF THE BLUEPRINT 213 00:10:03,004 --> 00:10:03,638 INTEROCEPTION PROGRAM. 214 00:10:03,638 --> 00:10:08,877 THERE'S BEEN REMARKABLE 215 00:10:08,877 --> 00:10:11,346 DISCOVERIES JUST MY KNOWLEDGE 216 00:10:11,346 --> 00:10:15,917 THE INTERACTION BETWEEN THE 217 00:10:15,917 --> 00:10:17,051 NERVOUS SYSTEM AND IMMUNE SYSTEM 218 00:10:17,051 --> 00:10:18,720 AND IMMUNE SYSTEM IN THE GUT. 219 00:10:18,720 --> 00:10:20,655 EVEN HOW MAYBE A MONKEY WILL 220 00:10:20,655 --> 00:10:30,098 [NO AUDIO] 221 00:10:30,098 --> 00:10:34,335 SOME OF THESE AREAS ARE 222 00:10:34,335 --> 00:10:36,171 GROUNDBREAKING NEW PATHWAYS TO 223 00:10:36,171 --> 00:10:37,505 UNDERSTAND FUNCTION. 224 00:10:37,505 --> 00:10:39,207 AND NOW I THINK WE HAVE TOOLS TO 225 00:10:39,207 --> 00:10:43,378 STUDY THEM SO MUCH BETTER THAN 226 00:10:43,378 --> 00:10:44,312 THE PAST. 227 00:10:44,312 --> 00:10:45,880 THERE'S A CHANCE FOR LOTS OF 228 00:10:45,880 --> 00:10:46,181 PROGRESS. 229 00:10:46,181 --> 00:10:49,117 NOT ONLY IN HOW THE BRAIN IS 230 00:10:49,117 --> 00:10:51,853 RECEIVING INPUTS IN THE 231 00:10:51,853 --> 00:10:53,154 ASCENDING PATHWAYS BUT ALSO HOW 232 00:10:53,154 --> 00:10:55,023 IT'S CONTROLLING FUNCTION IN A 233 00:10:55,023 --> 00:11:00,795 DESCENDING PATHWAYS. 234 00:11:00,795 --> 00:11:04,933 IN 2020 WE HAD WORKSHOPS AND IN 235 00:11:04,933 --> 00:11:08,102 2021 WE AWARDED SEVEN PROJECTS 236 00:11:08,102 --> 00:11:10,772 WE'LL TALK ABOUT TODAY TOTALLING 237 00:11:10,772 --> 00:11:12,674 ABOUT $18.15 MILLION OVER FIVE 238 00:11:12,674 --> 00:11:16,611 YEARS AND THEY COVERED A VARIETY 239 00:11:16,611 --> 00:11:19,714 OF ASSOCIATIONS BETWEEN ORGAN 240 00:11:19,714 --> 00:11:25,720 TYPES SO WE HAVE PROJECTS ON 241 00:11:25,720 --> 00:11:27,922 STOMACH-BRAIN INTEROCEPTION. 242 00:11:27,922 --> 00:11:31,259 BRAIN AIRWAY CONTROL, 243 00:11:31,259 --> 00:11:33,661 TEMPERATURE SENSE NEURONS IN THE 244 00:11:33,661 --> 00:11:36,364 SYMPATHETIC ADIPOSE TISSUE. 245 00:11:36,364 --> 00:11:39,400 VAGAL SENSORY NEURONS 246 00:11:39,400 --> 00:11:43,338 INNERVATING THE LIVER. 247 00:11:43,338 --> 00:11:47,108 NEUROCIRCUITS FOR BREATHING AND 248 00:11:47,108 --> 00:11:49,878 SPINAL SENSORY GANGLIA AND GUT 249 00:11:49,878 --> 00:11:50,144 SENSATION. 250 00:11:50,144 --> 00:11:51,913 THOSE WERE THE MAIN TOPICS THAT 251 00:11:51,913 --> 00:11:54,782 WERE FUNDED AND AS CAN IMAGINE 252 00:11:54,782 --> 00:11:58,453 FROM THE TOPICS, THEY COVER A 253 00:11:58,453 --> 00:12:03,791 NUMBER OF ORGAN--TYPES BUT OF 254 00:12:03,791 --> 00:12:04,759 COURSE PRETTY SMALL PERCENTAGE 255 00:12:04,759 --> 00:12:09,397 OF THE BODY REPRESENTED. 256 00:12:09,397 --> 00:12:10,665 THERE'S A LOT OF REAL ESTATE YET 257 00:12:10,665 --> 00:12:12,500 TO BE EXPLORED. 258 00:12:12,500 --> 00:12:15,069 THE PATHWAYS ARE PRIMARILY VAGAL 259 00:12:15,069 --> 00:12:18,506 AND SPINAL AND THE BRAIN AREAS 260 00:12:18,506 --> 00:12:21,175 THAT HAVE BEEN TIED IN THE 261 00:12:21,175 --> 00:12:22,911 SYSTEMS ARE SEEN ON THE RIGHT. 262 00:12:22,911 --> 00:12:26,848 THE GENERAL RULE IS THAT IT THE 263 00:12:26,848 --> 00:12:30,485 TIES OR INPUTS AND OUTPUTS ARE 264 00:12:30,485 --> 00:12:36,291 INVOLVING THE BRAIN STEM, 265 00:12:36,291 --> 00:12:38,560 HYPOTHALAMUS, SOME HIGHER AREAS 266 00:12:38,560 --> 00:12:44,399 AND INSULAR CORTEX AND AMYGDALA 267 00:12:44,399 --> 00:12:47,902 AND PRE FRONTAL CORTEX AND 268 00:12:47,902 --> 00:12:51,239 ILLUSTRATE THE IT GENERAL ROOTS 269 00:12:51,239 --> 00:12:54,776 THEY SAY WHEREBY THE 270 00:12:54,776 --> 00:12:55,643 INTEROCEPTIVE SYSTEM INTERACTS 271 00:12:55,643 --> 00:12:58,713 WITH THE BRAIN. 272 00:12:58,713 --> 00:13:01,149 A COUPLE EXAMPLES YOU'LL 273 00:13:01,149 --> 00:13:03,418 HOPEFULLY HEAR ABOUT IN MUCH 274 00:13:03,418 --> 00:13:05,553 MORE DETAIL THROUGHOUT THE DAY 275 00:13:05,553 --> 00:13:10,992 BUT THIS IS FROM A LAB IN MOUNT 276 00:13:10,992 --> 00:13:15,930 SINAI LOOK THE GLP1 SYSTEM. 277 00:13:15,930 --> 00:13:18,766 IT'S A POPULAR DRUG RIGHT NOW 278 00:13:18,766 --> 00:13:20,335 FOR WEIGHT LOSS. 279 00:13:20,335 --> 00:13:23,071 PROBABLY WILL BE PRETTY 280 00:13:23,071 --> 00:13:26,908 REVOLUTIONARY IN REDUCING 281 00:13:26,908 --> 00:13:29,143 CARDIAC AND STROKE MORBIDITY AND 282 00:13:29,143 --> 00:13:32,180 HOW DOES IT ACT? 283 00:13:32,180 --> 00:13:35,350 WELL, THE GROUP WAS ABLE TO 284 00:13:35,350 --> 00:13:39,320 FIGURE OUT THE GLP-1 IN ITS 285 00:13:39,320 --> 00:13:42,256 NATURAL STATE IS REDUCED BY 286 00:13:42,256 --> 00:13:44,525 ENDOCRINE CELLS WHICH ARE FUNNY 287 00:13:44,525 --> 00:13:46,928 CELLS ON THE BORDER OF NEURONS 288 00:13:46,928 --> 00:13:49,430 AND WE MIGHT BE ABLE TO PROMOTE 289 00:13:49,430 --> 00:13:52,200 THEM SOME DAY TO NEURONS. 290 00:13:52,200 --> 00:13:54,636 AND THERE'S EVIDENCE THEY DO 291 00:13:54,636 --> 00:13:59,207 MAKE SYNAPSES WITH SOME VAGAL 292 00:13:59,207 --> 00:14:05,213 AFERENCE BUT IN THIS SYSTEM THEY 293 00:14:05,213 --> 00:14:13,655 ARE RELEASING GLP1 TO NEURONS 294 00:14:13,655 --> 00:14:15,923 AND THERE'S AN OUTPUT TO THE 295 00:14:15,923 --> 00:14:20,928 STOMACH AND THE INTESTINAL TRACT 296 00:14:20,928 --> 00:14:23,931 TO SLOW DOWN MOTILITY WHICH 297 00:14:23,931 --> 00:14:27,201 WOULD MAKE YOU FEEL FULL AND 298 00:14:27,201 --> 00:14:28,703 GOES TO THE HYPOTHALAMUS FOR 299 00:14:28,703 --> 00:14:32,473 APPETITE SUPPRESSION AND WHEN 300 00:14:32,473 --> 00:14:35,710 YOU KNOCK OUT THESE FUGAL FIBER 301 00:14:35,710 --> 00:14:37,278 NEURONS YOU LOST THE EFFECT OF 302 00:14:37,278 --> 00:14:38,579 THE GLP1. 303 00:14:38,579 --> 00:14:41,149 NICE ABILITY NOW TO USE THESE 304 00:14:41,149 --> 00:14:45,720 KINDS OF TOOLS TO DISSECT OUT 305 00:14:45,720 --> 00:14:47,655 THE CIRCUITS BY KNOCKING OUT 306 00:14:47,655 --> 00:14:48,222 DIFFERENT STEPS. 307 00:14:48,222 --> 00:14:51,793 HERE'S ANOTHER ONE AND I SHOULD 308 00:14:51,793 --> 00:14:54,095 SAY WENT INTO NEUROLOGY TO GET 309 00:14:54,095 --> 00:14:55,663 AWAY FROM THE G.I. TRACT BUT IT 310 00:14:55,663 --> 00:14:59,067 SEEMS TO BE FOLLOWING ME AND NOT 311 00:14:59,067 --> 00:15:00,768 LETTING ME GET AWAY AND THIS IS 312 00:15:00,768 --> 00:15:03,905 FROM THE UNIVERSITY OF MICHIGAN 313 00:15:03,905 --> 00:15:09,277 LOOKING AT OSCILLATIONS IN BRAIN 314 00:15:09,277 --> 00:15:10,445 FOLD ACTIVITY LINKED TO GASTRIC 315 00:15:10,445 --> 00:15:12,013 SLOW WAIVES YOU CAN SEE IN THE 316 00:15:12,013 --> 00:15:17,618 TOP AND WHEN YOU DO A VAGOTOMY 317 00:15:17,618 --> 00:15:19,353 YOU DON'T SEE THE ACTIVITY IN 318 00:15:19,353 --> 00:15:19,921 THE BRAIN. 319 00:15:19,921 --> 00:15:27,929 WHY THE BRAIN NEEDS TO DO THIS 320 00:15:27,929 --> 00:15:34,602 SO CLEARLY ABSOLUTE 321 00:15:34,602 --> 00:15:35,803 INCONTROVERTIBLE FINDING AND 322 00:15:35,803 --> 00:15:38,172 HERE'S ANOTHER ONE LOOKING AT 323 00:15:38,172 --> 00:15:43,311 BREATHING CONTROL. 324 00:15:43,311 --> 00:15:50,384 INCREDIBLY IMPORTANT NOW 325 00:15:50,384 --> 00:15:52,954 CRITICAL NOW WITH FENTANYL 326 00:15:52,954 --> 00:15:54,655 CUTTING OFF YOUR BREATHING 327 00:15:54,655 --> 00:15:57,358 CIRCUITS AND THIS IS HOW HYPOXIA 328 00:15:57,358 --> 00:16:00,428 AFFECTING SIGHING AS PART OF THE 329 00:16:00,428 --> 00:16:02,730 CIRCUIT. 330 00:16:02,730 --> 00:16:05,600 THE CAROTID BODY PICK UP THE 331 00:16:05,600 --> 00:16:07,902 HYPOXIC SIGNAL AND SENDS A 332 00:16:07,902 --> 00:16:12,440 SIGNAL THROUGH THE JUGULAR 333 00:16:12,440 --> 00:16:18,146 GANGLION COMPLEX TO THE NUCLEUS 334 00:16:18,146 --> 00:16:21,415 AND THE CIRCUIT LOCATION FOR 335 00:16:21,415 --> 00:16:24,118 RESPIRATORY MOVEMENTS AND THAT 336 00:16:24,118 --> 00:16:27,622 IS WHAT TRIGGERS THE SIGH. 337 00:16:27,622 --> 00:16:29,624 WE'RE NOT ALL SIGHING BECAUSE 338 00:16:29,624 --> 00:16:36,597 WE'RE HYPOXIC. 339 00:16:36,597 --> 00:16:38,432 WE ALL SIGH BUT THERE'S PROBABLY 340 00:16:38,432 --> 00:16:40,034 OTHER THINGS THAT GO INTO THIS 341 00:16:40,034 --> 00:16:42,570 COMPLEX TO GET US TO SIGH AND 342 00:16:42,570 --> 00:16:44,438 SOMETIMES YAWN I GUESS PROBABLY 343 00:16:44,438 --> 00:16:49,310 AS WELL. 344 00:16:49,310 --> 00:16:52,446 AND THIS AGAIN IS INVOLVED IN 345 00:16:52,446 --> 00:16:56,117 THE BREATHING SECTOR AND THE 346 00:16:56,117 --> 00:16:57,752 SERIOUS PROBLEM WHICH IS SUDDEN 347 00:16:57,752 --> 00:17:02,190 DEATH AND EPILEPSY. 348 00:17:02,190 --> 00:17:08,429 IT'S BEEN -- IT'S STILL DEBATED 349 00:17:08,429 --> 00:17:11,532 AND HIGHLY STUDIED AS TO WHY 350 00:17:11,532 --> 00:17:14,001 KIDS DIE DURING AN EPILEPTIC 351 00:17:14,001 --> 00:17:14,569 SESURE. 352 00:17:14,569 --> 00:17:16,971 THE QUESTION HAS ALWAYS BEEN SIT 353 00:17:16,971 --> 00:17:19,106 CARDIAC OR SOMETIMES THE 354 00:17:19,106 --> 00:17:22,910 CHANNELS THAT CAUSE THE SEIZURE 355 00:17:22,910 --> 00:17:25,513 ALSO AFFECT THE HEART. 356 00:17:25,513 --> 00:17:26,981 THERE'S A LOT OF EVIDENCE IT 357 00:17:26,981 --> 00:17:28,449 INVOLVES THE RESPIRATORY TRACT 358 00:17:28,449 --> 00:17:30,518 AND IN THE MICE WHICH ARE 359 00:17:30,518 --> 00:17:34,889 MUTATION THAT IS SIMILAR TO WHAT 360 00:17:34,889 --> 00:17:45,766 IS SEEN IN CERTAIN SIN DROYNDRO 361 00:17:45,766 --> 00:17:53,407 KIDS THAT IS SIMILAR TO GERVAIS 362 00:17:53,407 --> 00:17:58,379 TRIGGER RESPIRATORY ARREST. 363 00:17:58,379 --> 00:18:01,816 WHAT THEY SEE IN THE MUTATED 364 00:18:01,816 --> 00:18:04,785 NICE IT'S IN THE EXCITATORY 365 00:18:04,785 --> 00:18:15,296 NEURONS THEY SEE SEIZURES AND 366 00:18:16,397 --> 00:18:20,434 AFTER THE SEIZURE ENDS IN THE 367 00:18:20,434 --> 00:18:25,206 ANNALS -- ANIMALS THAT STOP 368 00:18:25,206 --> 00:18:26,540 BREATHING YOU SEE WHAT IS 369 00:18:26,540 --> 00:18:28,376 ASSOCIATED WITH ABROGATION OF 370 00:18:28,376 --> 00:18:28,643 BREATHING. 371 00:18:28,643 --> 00:18:31,245 THEY ALL STOP BREATHING DURING 372 00:18:31,245 --> 00:18:34,382 THE SEIZURE BUT IN THE ANIMALS 373 00:18:34,382 --> 00:18:37,084 THAT DIE THEY NEVER REGAIN 374 00:18:37,084 --> 00:18:39,053 BREATHING AND THE HEART RATE 375 00:18:39,053 --> 00:18:39,921 KEEPS GOING FOR MINUTES AFTER 376 00:18:39,921 --> 00:18:46,527 THIS EVENT BUT THE BREATHINGS 377 00:18:46,527 --> 00:18:51,299 ARE STOPPED. 378 00:18:51,299 --> 00:18:53,267 BY UNDERSTANDING SOME PATHWAYS I 379 00:18:53,267 --> 00:18:55,569 THINK WE LEARN THINGS THAT ARE 380 00:18:55,569 --> 00:18:56,537 INTERESTING AND LEARNING THINGS 381 00:18:56,537 --> 00:18:58,806 THAT ARE ACTIONABLE AND THINGS 382 00:18:58,806 --> 00:19:00,441 THAT ARE INTERESTING MAY NOT BE 383 00:19:00,441 --> 00:19:01,676 ACTIONABLE TODAY BUT MAY BE 384 00:19:01,676 --> 00:19:02,643 ACTIONABLE TOMORROW. 385 00:19:02,643 --> 00:19:04,378 I THINK IT'S A FERTILE FIELD AND 386 00:19:04,378 --> 00:19:07,815 IT'S FASCINATING TO ME AND 387 00:19:07,815 --> 00:19:09,450 LOOKING FORWARD TO LEARNING FROM 388 00:19:09,450 --> 00:19:09,984 THE GROUP TODAY. 389 00:19:09,984 --> 00:19:20,328 SO THANKS VERY MUCH. 390 00:19:31,872 --> 00:19:34,942 >> THANK YOU, DR. KOROSHETZ. 391 00:19:34,942 --> 00:19:36,444 YOUR STAUNCH SUPPORT FOR THIS 392 00:19:36,444 --> 00:19:43,751 TOPIC MEANS A LOT. 393 00:19:43,751 --> 00:19:46,187 THIS IS HOW YOU CAN GET IN 394 00:19:46,187 --> 00:19:47,888 CONTACT WITH DR. KOROSHETZ AND 395 00:19:47,888 --> 00:19:54,695 HAS A TWITTER ACCOUNT ACTUALLY. 396 00:19:54,695 --> 00:19:54,895 OKAY. 397 00:19:54,895 --> 00:19:57,264 SO I AM NOW GOING TO CONTINUE TO 398 00:19:57,264 --> 00:19:59,133 SHARE MORE HOW THIS BLUEPRINT 399 00:19:59,133 --> 00:20:04,138 INITIATIVE HAS REALLY IGNITED 400 00:20:04,138 --> 00:20:10,544 AND STIMULATED THE TRANS-NIH 401 00:20:10,544 --> 00:20:12,346 PORTION OF THIS AND I'M A BRANCH 402 00:20:12,346 --> 00:20:16,350 CHIEF WITHIN THE DIVISION OF 403 00:20:16,350 --> 00:20:18,019 EXTRAMURAL RESEARCH AT NCCIH. 404 00:20:18,019 --> 00:20:19,453 FIRST I WANTED TO HIGHLIGHT 405 00:20:19,453 --> 00:20:23,457 THESE EFFORTS THAT YOU HEARD 406 00:20:23,457 --> 00:20:25,159 ABOUT AND YOU'LL HEAR ABOUT IS 407 00:20:25,159 --> 00:20:30,131 REALLY SUPPORTED AND LED BY A 408 00:20:30,131 --> 00:20:32,400 LARGE TEAM OF PROGRAM AND REVIEW 409 00:20:32,400 --> 00:20:33,934 OFFICERS WITHIN NIH INCLUDING 410 00:20:33,934 --> 00:20:43,010 MORE THAN 25 OF US AS WELL AS AT 411 00:20:43,010 --> 00:20:45,479 LEAST 15 NIH INSTITUTES AND 412 00:20:45,479 --> 00:20:47,948 CENTER AND WE'RE ALL PASSIONATE 413 00:20:47,948 --> 00:20:50,584 SUPPORTERS FOR YOU AND MANY WORK 414 00:20:50,584 --> 00:20:52,053 TIRELESSLY BEHIND THE SCENE TO 415 00:20:52,053 --> 00:20:53,287 HELP GROW THIS VERY IMPORTANT 416 00:20:53,287 --> 00:20:54,855 FIELD. 417 00:20:54,855 --> 00:20:56,290 MANY ARE HERE TODAY AND YOU'LL 418 00:20:56,290 --> 00:21:01,829 SEE SOME OF THEM ON STAGE LATER. 419 00:21:01,829 --> 00:21:04,365 SO I KNOW I'VE HEARD QUITE A BIT 420 00:21:04,365 --> 00:21:06,067 ABOUT THE COMMUNITY SAYING, WHAT 421 00:21:06,067 --> 00:21:08,202 A WONDERFUL PROGRAM YOU HAVE 422 00:21:08,202 --> 00:21:08,636 BILLED TODAY. 423 00:21:08,636 --> 00:21:11,906 I WISH I COULD TAKE CREDIT BUT I 424 00:21:11,906 --> 00:21:14,842 CAN'T BECAUSE THIS IS REALLY A 425 00:21:14,842 --> 00:21:17,445 PRODUCT OF MANY BRILLIANT MINDS 426 00:21:17,445 --> 00:21:18,479 IN OUR PLANNING COMMITTEE. 427 00:21:18,479 --> 00:21:24,318 IN PARTICULAR THE SIX NON-NIH 428 00:21:24,318 --> 00:21:25,319 SCIENTISTS WHO HAVE MET WITH US 429 00:21:25,319 --> 00:21:28,355 AND VOLUNTEERED TO JOIN THE 430 00:21:28,355 --> 00:21:29,890 PLANNING COMMITTEE SINCE LAST 431 00:21:29,890 --> 00:21:32,560 WINTER AND MET WITH US MONTHLY 432 00:21:32,560 --> 00:21:34,695 TO PLAN THIS PROGRAM AND HELPED 433 00:21:34,695 --> 00:21:37,798 TO SELECT THE SPEAKERS, EVALUATE 434 00:21:37,798 --> 00:21:39,934 HUNDREDS OF POSTER SUBMISSIONS 435 00:21:39,934 --> 00:21:41,268 AND SELECTED THE FLASH TALK 436 00:21:41,268 --> 00:21:43,804 SPEAKERS AS WELL AND THIS IS 437 00:21:43,804 --> 00:21:45,506 REALLY WHY WE HAVE THIS 438 00:21:45,506 --> 00:21:46,674 WONDERFUL LINEUP TODAY AND IN 439 00:21:46,674 --> 00:21:51,912 PARTICULAR I WANTED TO 440 00:21:51,912 --> 00:22:02,423 ACKNOWLEDGE DR. AJIJOLA AND 441 00:22:11,232 --> 00:22:14,201 ANDEMANN AND DR. XIN SUN FROM 442 00:22:14,201 --> 00:22:15,936 UCSD AND MY COLLEAGUES FROM NIH 443 00:22:15,936 --> 00:22:18,506 ON THE RIGHT SIDE OF THE SLIDE. 444 00:22:18,506 --> 00:22:23,010 THIS MEETING IS ALSO NOT 445 00:22:23,010 --> 00:22:26,447 POSSIBLE WITHOUT THE SUPPORT OF 446 00:22:26,447 --> 00:22:27,915 THE GENEROUS FINANCIAL SUPPORT 447 00:22:27,915 --> 00:22:30,017 AND LOGISTIC SUPPORT FROM THE 448 00:22:30,017 --> 00:22:34,722 NIH, IN PARTICULAR THE OFFICE OF 449 00:22:34,722 --> 00:22:38,092 COMMUNICATION WHO RESCUED YOU US 450 00:22:38,092 --> 00:22:41,962 FROM A POTENTIAL DEBACLE ON THE 451 00:22:41,962 --> 00:22:43,931 NIH CAMPUS AND PAID NOR VENUE TO 452 00:22:43,931 --> 00:22:45,533 MEET TODAY TO EXPAND THIS 453 00:22:45,533 --> 00:22:47,468 MEETING TO SUPPORT MORE THAN 400 454 00:22:47,468 --> 00:22:50,337 PEOPLE WHO WILL BE COMING TODAY 455 00:22:50,337 --> 00:22:55,109 TO JOIN THIS EVENT. 456 00:22:55,109 --> 00:22:58,179 ALSO THE BLUEPRINT HAS 457 00:22:58,179 --> 00:22:59,213 GENEROUSLY SUPPORT THE TRAVEL OF 458 00:22:59,213 --> 00:23:00,281 YOUNG AWARDEES AND IN PARTICULAR 459 00:23:00,281 --> 00:23:03,017 I WANT TO THANK THE INVITED 460 00:23:03,017 --> 00:23:05,019 SPEAKERS WHO HAVE REALLY 461 00:23:05,019 --> 00:23:07,755 VOLUNTEERED THEIR RESOURCE TO 462 00:23:07,755 --> 00:23:09,523 COME ON THEIR OWN TO ALLOCATE 463 00:23:09,523 --> 00:23:14,862 THE RESOURCE TO SUPPORT THE 464 00:23:14,862 --> 00:23:18,499 YOUNG INVESTIGATORS TODAY. 465 00:23:18,499 --> 00:23:20,534 I WANT TO THANK THE KEYNOTE 466 00:23:20,534 --> 00:23:24,371 SPEAKERS AND THE OFFICE OF 467 00:23:24,371 --> 00:23:27,174 BEHAVIOR AND SOCIAL RESEARCH OF 468 00:23:27,174 --> 00:23:30,311 NIH OBSSR TO HAVE THE LIVE CAST 469 00:23:30,311 --> 00:23:32,112 THROUGH THE NIH VIDEOCAST AND 470 00:23:32,112 --> 00:23:33,714 THE WONDERFUL STAFF WORKING HERE 471 00:23:33,714 --> 00:23:37,851 SINCE LAST NIGHT TO MAKING SURE 472 00:23:37,851 --> 00:23:39,553 IT WOULD RUN SMOOTHLY. 473 00:23:39,553 --> 00:23:44,458 HERE'S THE LIST OF THE TRAVEL 474 00:23:44,458 --> 00:23:50,731 AWARDEES THAT SUPPORTED BY NIH 475 00:23:50,731 --> 00:23:53,067 BLUEPRINT AND YOU'LL HEAR FROM 476 00:23:53,067 --> 00:23:55,369 SIX OF THEM SOON AS FLASH TALK 477 00:23:55,369 --> 00:23:56,437 PRESENTERS BUT I WANTED TO 478 00:23:56,437 --> 00:23:58,339 HIGHLIGHT THOSE WHO DIDN'T GET 479 00:23:58,339 --> 00:24:00,708 TO PRESENT A FLASH TALK BUT WILL 480 00:24:00,708 --> 00:24:02,710 BE PRESENTING POSTERS AND HAVE 481 00:24:02,710 --> 00:24:04,211 WONDERFUL WORK TO SHARE WITH YOU 482 00:24:04,211 --> 00:24:05,312 TODAY AS WELL AND AN ENCOURAGE 483 00:24:05,312 --> 00:24:08,115 YOU TO CHECK OUT THEIR POSTERS. 484 00:24:08,115 --> 00:24:09,416 THE THINGS ARE MISALIGNED BUT 485 00:24:09,416 --> 00:24:11,285 I'LL READ THEIR NAME. 486 00:24:11,285 --> 00:24:15,089 DR. HARRAZ FROM UNIVERSITY OF 487 00:24:15,089 --> 00:24:15,389 VERMONT. 488 00:24:15,389 --> 00:24:18,225 DR. JACKMAN FROM COLUMBIA 489 00:24:18,225 --> 00:24:23,063 UNIVERSITY AND DR. TRUONG LY 490 00:24:23,063 --> 00:24:31,205 FROM USSF AND DR. SAHASRABUDHE 491 00:24:31,205 --> 00:24:33,007 FROM M.I.T. 492 00:24:33,007 --> 00:24:36,477 I'M SORRY IF I MISPRONOUNCED 493 00:24:36,477 --> 00:24:40,681 YOUR LAST NAME. 494 00:24:40,681 --> 00:24:43,117 USING THE NIH REPORTER THIS IS 495 00:24:43,117 --> 00:24:44,551 OPEN RESOURCE ANYBODY CAN USE. 496 00:24:44,551 --> 00:24:48,422 WE HAVE DONE SOME ANALYSIS SEE 497 00:24:48,422 --> 00:24:50,824 THE IMPACT WHATEVER WE'VE DONE 498 00:24:50,824 --> 00:24:55,496 ACROSS THE NIH AND INTERESTING. 499 00:24:55,496 --> 00:24:59,066 2018 IS THE TIME THE NIH 500 00:24:59,066 --> 00:25:00,334 BLUEPRINT WAS STARTED TO PLAN 501 00:25:00,334 --> 00:25:03,170 THE WORKSHOP AND THAT PLANNING 502 00:25:03,170 --> 00:25:05,773 SOMEHOW CORRELATED WITH A BIG 503 00:25:05,773 --> 00:25:09,043 JUMP OF ALMOST NOTHING TO OVER 504 00:25:09,043 --> 00:25:15,449 10 WITHIN THE NIH DEDICATED THE 505 00:25:15,449 --> 00:25:17,418 TOPIC OF INTEROCEPTION USING THE 506 00:25:17,418 --> 00:25:18,986 TERM IN THEIR APPLICATION AND 507 00:25:18,986 --> 00:25:21,789 YOU CAN SEE NICE GROWTH ON THE 508 00:25:21,789 --> 00:25:23,524 NUMBER OF NIH GRANTS FUNNED ON 509 00:25:23,524 --> 00:25:26,760 THE TOP OF INTEROCEPTION AND 510 00:25:26,760 --> 00:25:31,065 TODAY WE HAVE BETWEEN 60 AND 70 511 00:25:31,065 --> 00:25:33,434 ACTIVE GRANTS IN THE FISCAL 512 00:25:33,434 --> 00:25:34,168 2023. 513 00:25:34,168 --> 00:25:36,904 MORE THAN A FIVEFOLD INCREASE. 514 00:25:36,904 --> 00:25:39,406 THAT'S CORRELATED WITH A NICE 515 00:25:39,406 --> 00:25:44,545 FUNDING, SPENDING AS WELL FROM 516 00:25:44,545 --> 00:25:50,117 ALMOST NOTHING PRIOR TO 2018 AND 517 00:25:50,117 --> 00:25:53,520 NOW BETWEEN $20 MILLION AND $30 518 00:25:53,520 --> 00:25:54,788 MILLION ON THE TOPIC OF 519 00:25:54,788 --> 00:25:55,356 INTEROCEPTION. 520 00:25:55,356 --> 00:25:57,624 THIS IS PROBABLY NOT EASY TO SEE 521 00:25:57,624 --> 00:26:00,094 BUT IT'S A DIAGRAM GENERATE THE 522 00:26:00,094 --> 00:26:02,763 NIH REPORTER TO SHOW THE CURRENT 523 00:26:02,763 --> 00:26:05,532 SNAPSHOT OF THE TYPE OF TOPICS 524 00:26:05,532 --> 00:26:10,170 ASSOCIATED BUT FUNDED IN 525 00:26:10,170 --> 00:26:12,039 INTEROCEPTION RESEARCH AT NIH 526 00:26:12,039 --> 00:26:14,241 INCLUDING RELATED TO TALKS SUCH 527 00:26:14,241 --> 00:26:18,812 AS PAIN AND EMOTIONAL REGULATION 528 00:26:18,812 --> 00:26:27,588 AND IN ADDITION TO NERVOUS 529 00:26:27,588 --> 00:26:28,589 SYSTEM AND INTEROCEPTION 530 00:26:28,589 --> 00:26:32,626 AWARENESS AND I WANT YOU TO TAKE 531 00:26:32,626 --> 00:26:39,933 THIS TOPIC AND A SNAPSHOT AND 532 00:26:39,933 --> 00:26:43,270 HURE -- SURE IN A FEW YEARS WITH 533 00:26:43,270 --> 00:26:44,705 YOUR EFFORTS THIS WILL TRANSFORM 534 00:26:44,705 --> 00:26:45,839 IN MANY WAYS. 535 00:26:45,839 --> 00:26:54,114 AND LOOKING AT HOW THE NIH 536 00:26:54,114 --> 00:26:56,216 ENDEAVOR CHANGE THE SEARCH ON 537 00:26:56,216 --> 00:26:57,084 THE TOPIC OF INTEROCEPTION. 538 00:26:57,084 --> 00:27:00,921 RED BARS IS FUNDED BY NIH GRANTS 539 00:27:00,921 --> 00:27:03,490 AND THE BLUE IS THE PUB MED 540 00:27:03,490 --> 00:27:04,358 SEARCH. 541 00:27:04,358 --> 00:27:06,593 THE GLOBAL RESEARCH RELATED TO 542 00:27:06,593 --> 00:27:06,927 INTEROCEPTION. 543 00:27:06,927 --> 00:27:11,565 YOU CAN SEE OVER THE YEARS THE 544 00:27:11,565 --> 00:27:12,499 NIH FUNDED RESEARCH ON 545 00:27:12,499 --> 00:27:17,438 INTEROCEPTION HAS BECOME MORE 546 00:27:17,438 --> 00:27:18,138 DOMINANT CONTRIBUTOR TO THE 547 00:27:18,138 --> 00:27:18,972 LITERATURE INTEROCEPTION 548 00:27:18,972 --> 00:27:19,339 RESEARCH. 549 00:27:19,339 --> 00:27:23,010 IT'S WONDERFUL TO SEE THAT KIND 550 00:27:23,010 --> 00:27:23,811 OF CHANGE. 551 00:27:23,811 --> 00:27:30,250 NOW, YOU WONDER HOW CAN I GET 552 00:27:30,250 --> 00:27:32,252 FUNDING OPPORTUNITIES TO SUPPORT 553 00:27:32,252 --> 00:27:32,753 MY WORK. 554 00:27:32,753 --> 00:27:36,657 I LEARNED HOW TO MAKE QR CODES 555 00:27:36,657 --> 00:27:38,759 SO I'LL USE THEM A LOT TODAY. 556 00:27:38,759 --> 00:27:42,062 THIS QR CODE WILL LEAD YOU TO A 557 00:27:42,062 --> 00:27:46,867 WEBSITE CALLED NIH GRANTS AND 558 00:27:46,867 --> 00:27:50,737 FUNDING AND HAS OPPORTUNITIES 559 00:27:50,737 --> 00:27:51,271 RELATED TO INTEROCEPTION 560 00:27:51,271 --> 00:27:51,972 RESEARCH ACROSS THE NIH. 561 00:27:51,972 --> 00:28:02,516 IN ADDITION TO NOTICE OF SPECIAL 562 00:28:03,150 --> 00:28:09,056 INTEREST AND THE NATIONAL CANCER 563 00:28:09,056 --> 00:28:17,431 INSTITUTE OPPORTUNITY RELATED TO 564 00:28:17,431 --> 00:28:19,032 INTEROCEPTION AND LOOK AT 565 00:28:19,032 --> 00:28:21,935 INTEROCEPTIVE OUTCOME MEASURES. 566 00:28:21,935 --> 00:28:27,908 THE TOPIC STILL CUTTING EDGE 567 00:28:27,908 --> 00:28:32,813 BECAUSE PRETTY SUBSTANTIAL 568 00:28:32,813 --> 00:28:34,348 RESEARCH COMES FROM THE HIGH 569 00:28:34,348 --> 00:28:35,916 RISK, HIGH REWARD PROGRAM AND 570 00:28:35,916 --> 00:28:38,619 THE SECOND QR WILL TAKE YOU TO 571 00:28:38,619 --> 00:28:39,920 THE WEBSITE ABOUT COMMON FUND 572 00:28:39,920 --> 00:28:42,356 AND TAKE A GOOD LOOK AT IT AND 573 00:28:42,356 --> 00:28:44,491 IT COVERS A WIDE RANGE OF 574 00:28:44,491 --> 00:28:45,926 RESEARCH OPPORTUNITIES 575 00:28:45,926 --> 00:28:50,898 SUPPORTING FROM GRADUATE 576 00:28:50,898 --> 00:28:52,432 STUDENTS TO INVESTIGATORS AND 577 00:28:52,432 --> 00:28:56,436 THEY ALSO HAVE A WAY CALLED 578 00:28:56,436 --> 00:29:01,108 TRANSFORMATIVE RO1 TO COMPETE 579 00:29:01,108 --> 00:29:01,708 ANONYMOUSLY FOR POTENTIAL BIG 580 00:29:01,708 --> 00:29:03,810 FINANCIAL SUPPORT. 581 00:29:03,810 --> 00:29:06,513 I WANTED TO ALSO SHARE WITH 582 00:29:06,513 --> 00:29:08,115 YOU -- I WAS TRYING TO TALK 583 00:29:08,115 --> 00:29:10,984 ABOUT THIS BUT MY PRESENTATION 584 00:29:10,984 --> 00:29:11,885 GOT BOTCHED BECAUSE OF TECHNICAL 585 00:29:11,885 --> 00:29:14,421 PROBLEMS BUT TODAY I WANTED TO 586 00:29:14,421 --> 00:29:17,724 REALLY BRING TO YOUR ATTENTION 587 00:29:17,724 --> 00:29:20,561 ABOUT THERE'S A STUDY SECTION 588 00:29:20,561 --> 00:29:23,263 WITHIN THE NIH THAT IS DEDICATED 589 00:29:23,263 --> 00:29:27,834 RESEARCH ABOUT NEUROSCIENCE OF 590 00:29:27,834 --> 00:29:29,303 INTEROCEPTION AND SENSATION AND 591 00:29:29,303 --> 00:29:34,575 I'M SORRY THIS ALIGNMENT HERE 592 00:29:34,575 --> 00:29:38,779 WHO IS THE REVIEW OFFICER TO RUN 593 00:29:38,779 --> 00:29:43,917 THE STUDY SECTION IS A NEW 594 00:29:43,917 --> 00:29:45,085 MEMBER OF THE INTEROCEPTION 595 00:29:45,085 --> 00:29:54,294 WORKING GROUP AND CHECK OUT HIS 596 00:29:54,294 --> 00:29:58,332 QR CODE AND MAYBE SEND AN 597 00:29:58,332 --> 00:30:00,400 APPLICATION TO THE STUDY SECTION 598 00:30:00,400 --> 00:30:05,172 AND WANT MEDDED -- WANT NODE 599 00:30:06,873 --> 00:30:08,375 THIS WANTED KNOW SHARE THIS TOOL 600 00:30:08,375 --> 00:30:13,347 AND IF YOU PLUG IN YOUR ABSTRACT 601 00:30:13,347 --> 00:30:15,616 OR SPECIFIC AIMS PAGE INTO THE 602 00:30:15,616 --> 00:30:17,884 SYSTEM, IT WILL TELL YOU WHICH 603 00:30:17,884 --> 00:30:19,386 STUDY SECTION YOU'RE APPLICATION 604 00:30:19,386 --> 00:30:21,054 MAY GET ROUTED TO AND CHECK OUT 605 00:30:21,054 --> 00:30:21,955 THE STUDY SECTION. 606 00:30:21,955 --> 00:30:24,458 OBVIOUSLY, IF YOU HAVE A STUDY 607 00:30:24,458 --> 00:30:27,127 SECTION IN MIND YOU MIGHT WANT 608 00:30:27,127 --> 00:30:28,996 TO TWEAK YOUR WORDS TO TAKE YOU 609 00:30:28,996 --> 00:30:32,099 TO THAT STUDY SECTION IN THE 610 00:30:32,099 --> 00:30:33,433 ABSTRACT OR SPECIFIC AIMS PAGE. 611 00:30:33,433 --> 00:30:37,004 LASTLY, I WANTED TO SHARE THIS 612 00:30:37,004 --> 00:30:39,906 INCREDIBLE NEW COMING MEETING 613 00:30:39,906 --> 00:30:47,914 SERIES AND THIS IS REALLY LEAD 614 00:30:47,914 --> 00:30:54,287 BY DR. SUN AND DR. ANDERMANN AND 615 00:30:54,287 --> 00:30:54,855 DR. COSTA. 616 00:30:54,855 --> 00:30:55,922 THREE WORKED TIRELESSLY BEHIND 617 00:30:55,922 --> 00:30:59,426 THE SCENES FROM LAST YEAR TO 618 00:30:59,426 --> 00:31:00,727 APPLY AND SUCCESSIVELY GAIN THE 619 00:31:00,727 --> 00:31:05,699 SUPPORT FROM KEY STONE SYMPOSIUM 620 00:31:05,699 --> 00:31:07,668 WITH SUPPORT AND NOW IT WILL 621 00:31:07,668 --> 00:31:12,939 OPEN UP A NEW SERIES CONFERENCE 622 00:31:12,939 --> 00:31:14,775 SERIES ON INTEROCEPTION STARTING 623 00:31:14,775 --> 00:31:17,911 SOME TIME IN SPRING OF 2025. 624 00:31:17,911 --> 00:31:20,647 THE RUMOR I HEARD IS THE 625 00:31:20,647 --> 00:31:25,218 LOCATION WILL BE AT AN EXCITING 626 00:31:25,218 --> 00:31:29,022 PLACE ASSOCIATED WITH ONE OF 627 00:31:29,022 --> 00:31:29,823 THOSE THREE LEADERS. 628 00:31:29,823 --> 00:31:32,459 I CAN'T TELL YOU WHAT IT IS BUT 629 00:31:32,459 --> 00:31:34,294 STAY TUNED AND WE'LL REACH OUT 630 00:31:34,294 --> 00:31:35,529 AS THE INFORMATION BECOMES MORE 631 00:31:35,529 --> 00:31:36,997 PRONOUNCED AND WILL ALLOW US TO 632 00:31:36,997 --> 00:31:38,432 GET TOGETHER FOR THREE DAYS 633 00:31:38,432 --> 00:31:40,267 RATHER THAN ONE DAY TO DISCUSS 634 00:31:40,267 --> 00:31:45,505 THIS EXCITING AREA OF SCIENCE. 635 00:31:45,505 --> 00:31:47,340 LASTLY, THANK YOU FOR YOUR 636 00:31:47,340 --> 00:31:48,341 ATTENTION AND FEEL FREE TO REACH 637 00:31:48,341 --> 00:31:49,743 OUT TO US BY E-MAIL. 638 00:31:49,743 --> 00:31:51,378 THIS IS OUR COMMON E-MAIL BOX 639 00:31:51,378 --> 00:31:53,346 THE MANY OF US HAVE ACCESS TO 640 00:31:53,346 --> 00:31:54,848 AND WILL RESPOND TO AS SOON AS 641 00:31:54,848 --> 00:31:55,582 WE CAN. 642 00:31:55,582 --> 00:31:57,451 WE LOVE TO HEAR YOUR QUESTIONS 643 00:31:57,451 --> 00:31:59,619 AND ALSO SUGGESTIONS OF HOW WE 644 00:31:59,619 --> 00:32:02,289 CAN BETTER SUPPORT YOU AND WHAT 645 00:32:02,289 --> 00:32:03,423 ARE YOUR BIGGEST CHALLENGE IN 646 00:32:03,423 --> 00:32:05,726 YOUR RESEARCH BESIDES FUNDING, 647 00:32:05,726 --> 00:32:07,327 PER SE, BUT TECHNOLOGY AND 648 00:32:07,327 --> 00:32:12,499 TOPICS BECAUSE THAT WILL HELP US 649 00:32:12,499 --> 00:32:14,568 TO DEVELOP PROGRAMS TO SUPPORT 650 00:32:14,568 --> 00:32:15,736 YOU THE BEST AND THANK YOU VERY 651 00:32:15,736 --> 00:32:20,440 MUCH AND I'LL MOVE ON TO 652 00:32:20,440 --> 00:32:24,111 INTRODUCE MY WONDERFUL 653 00:32:24,111 --> 00:32:34,654 COLLEAGUE, DR. DANA SCHLOESSER 654 00:32:40,627 --> 00:32:42,562 AND WILL INTRODUCE AND MODERATE 655 00:32:42,562 --> 00:32:52,906 THE KEY NOTE SPEECH. 656 00:32:58,378 --> 00:33:01,581 >> GREAT. 657 00:33:01,581 --> 00:33:03,884 I HAVE THE HONOR OF INTRODUCING 658 00:33:03,884 --> 00:33:07,287 OUR KEY NOTE SPEAKER DR. KAY TYE 659 00:33:07,287 --> 00:33:09,990 AND WHEN SPEAKING ABOUT NEURAL 660 00:33:09,990 --> 00:33:11,391 MECHANISMS OF SOCIAL 661 00:33:11,391 --> 00:33:12,459 HOMEOSTASIS. 662 00:33:12,459 --> 00:33:14,661 KAY. 663 00:33:14,661 --> 00:33:15,862 I WOULD LOVE FOR YOU TO COME UP 664 00:33:15,862 --> 00:33:26,239 HERE AND GET STARTED. 665 00:33:27,274 --> 00:33:28,341 >> GOOD MORNING. 666 00:33:28,341 --> 00:33:35,715 THANK YOU SO MUCH FOR HAVING ME 667 00:33:35,715 --> 00:33:35,916 HERE. 668 00:33:35,916 --> 00:33:46,426 I ENJOYED THE INTRODUCT ORY 669 00:33:56,570 --> 00:33:56,770 SESSION. 670 00:33:56,770 --> 00:33:59,673 IT'S HUMBLING TO BE HERE IN THE 671 00:33:59,673 --> 00:34:02,576 PRESENCE OF GIANTS AND AS WE 672 00:34:02,576 --> 00:34:04,044 PREPPING FOR THE MEETING THEY 673 00:34:04,044 --> 00:34:05,579 MENTIONED WE'D LIKE THE KEY NOTE 674 00:34:05,579 --> 00:34:16,056 SPEAKER FROM OUTSIDE FIELD. 675 00:34:18,592 --> 00:34:22,362 I'VE BEEN STUDYING INTEROCEPTION 676 00:34:22,362 --> 00:34:27,868 FOR MY WHOLE CARREER FROM A 677 00:34:27,868 --> 00:34:38,311 SLIGHTLY DIFFERENT ANGLE. 678 00:34:50,724 --> 00:34:51,124 AND WE HAVE CHANGING 679 00:34:51,124 --> 00:34:51,758 ENVIRONMENTAL CONDITIONS AND HOW 680 00:34:51,758 --> 00:34:52,726 DO WE DECIDE WHICH POSTERS TO GO 681 00:34:52,726 --> 00:34:56,796 TO, OF COURSE. 682 00:34:56,796 --> 00:35:03,203 SO HOMEOSTASIS, MANY BODIES OF 683 00:35:03,203 --> 00:35:04,971 BEAUTIFUL WORK INCLUDING NOBEL 684 00:35:04,971 --> 00:35:08,008 PRIZE WINNING WORK INCLUDING 685 00:35:08,008 --> 00:35:08,608 THERMO REGULATION HAVE BEEN 686 00:35:08,608 --> 00:35:12,712 ELUCIDATED WITH HOMEOSTASIS. 687 00:35:12,712 --> 00:35:15,015 EVERY HOMEOSTATIC SYSTEM HAS 688 00:35:15,015 --> 00:35:17,150 DETECTERS THAT DETECT THE 689 00:35:17,150 --> 00:35:18,985 TEMPERATURE OF MY BODY, FEED 690 00:35:18,985 --> 00:35:21,855 THIS INPUT FORWARD TO A CONTROL 691 00:35:21,855 --> 00:35:28,228 CENTER THAT COMPUTES THE 692 00:35:28,228 --> 00:35:30,330 DIFFERENCE MANY OF SET POINT AND 693 00:35:30,330 --> 00:35:37,604 HIGHER THAN 98.6% THAT GOES TO A 694 00:35:37,604 --> 00:35:39,940 SYSTEM TO CHANGE THAT AND MOVE 695 00:35:39,940 --> 00:35:47,113 ME TO THE SHADE OR BEGIN 696 00:35:47,113 --> 00:35:49,416 PERSPIRING AND THIS INTERACTS 697 00:35:49,416 --> 00:35:51,551 WITH THE ENVIRONMENT TO MAKE THE 698 00:35:51,551 --> 00:35:55,288 CHANGE AND THESE ARE ESSENTIALLY 699 00:35:55,288 --> 00:36:00,427 INTEROCEPTION SO IT'S 700 00:36:00,427 --> 00:36:03,596 APREREQUISITE AND HOMEOSTASIS 701 00:36:03,596 --> 00:36:06,599 HAS BEEN A HOT TOPIC AND YET 702 00:36:06,599 --> 00:36:07,901 INTEROCEPTION HAS ALWAYS BEEN 703 00:36:07,901 --> 00:36:08,168 NECESSARY. 704 00:36:08,168 --> 00:36:10,303 WE THINK IT AS SENSING INTERNAL 705 00:36:10,303 --> 00:36:13,139 STATES, HUNGER, THIRST, ORGAN 706 00:36:13,139 --> 00:36:17,877 FUNCTION, IF YOU YOU HAVE TO PEE 707 00:36:17,877 --> 00:36:23,016 AND ALSO FROM SHARINGTON AND 708 00:36:23,016 --> 00:36:28,254 CRAIG EXPANDED THIS THIS 709 00:36:28,254 --> 00:36:30,824 INCLUDES EMOTIONAL PROCESSING 710 00:36:30,824 --> 00:36:35,195 AND PAIN AND WHAT IS SOCIAL 711 00:36:35,195 --> 00:36:35,729 HOMEOSTASIS. 712 00:36:35,729 --> 00:36:37,897 THAT REFERS TO TWO NESTED 713 00:36:37,897 --> 00:36:38,164 PROJECT. 714 00:36:38,164 --> 00:36:39,766 THIS IS ESSENTIALLY A PIONEER 715 00:36:39,766 --> 00:36:43,603 AWARD THAT WAS AWARDED IN 2016 716 00:36:43,603 --> 00:36:46,873 OR APPLIED FOR IN 2016 AND ALL 717 00:36:46,873 --> 00:36:49,809 THE WORK I'LL TALK ABOUT TODAY 718 00:36:49,809 --> 00:36:55,548 IS MADE POSSIBLE BY NCCIH. 719 00:36:55,548 --> 00:36:58,818 AND THE DREAM IS TO PREDICT HOW 720 00:36:58,818 --> 00:37:01,521 SOCIAL GROUPS OR SUPER 721 00:37:01,521 --> 00:37:02,288 ORGANISMAL GROUPS CAN FUNCTION 722 00:37:02,288 --> 00:37:04,524 BUT BEFORE WE CAN CREATE A 723 00:37:04,524 --> 00:37:06,226 PREDICTIVE DYNAMICAL MODEL AND 724 00:37:06,226 --> 00:37:09,896 CREATE A MODEL WE DON'T NEED AND 725 00:37:09,896 --> 00:37:13,299 WE CAN RUN SIMULATION AND WHY IS 726 00:37:13,299 --> 00:37:14,434 THAT SCIENCE FICTION? 727 00:37:14,434 --> 00:37:15,468 THAT'S SCIENCE FICTION BECAUSE 728 00:37:15,468 --> 00:37:17,604 WE'RE SO FAR FROM BUILDING AN 729 00:37:17,604 --> 00:37:19,039 ACCURATE MODEL FOR THE 730 00:37:19,039 --> 00:37:20,306 INDIVIDUAL BRAIN AND SO EVEN 731 00:37:20,306 --> 00:37:21,574 THOUGH WHEN I'M REALLY 732 00:37:21,574 --> 00:37:24,010 INTERESTED IN IS GROUP DYNAMICS, 733 00:37:24,010 --> 00:37:25,145 IT IS REALLY IMPORTANT TO START 734 00:37:25,145 --> 00:37:28,515 FROM A SOLID FOUNDATION. 735 00:37:28,515 --> 00:37:29,315 THAT'S A LOT OF THE WORK I'M 736 00:37:29,315 --> 00:37:31,618 GOING TO TALK ABOUT. 737 00:37:31,618 --> 00:37:34,287 AND WHY DO I EVEN THINK THERE'S 738 00:37:34,287 --> 00:37:38,925 SUCH A THING AS SOCIO 739 00:37:38,925 --> 00:37:39,325 HOMEOSTASIS. 740 00:37:39,325 --> 00:37:40,794 IT'S NOT LIKE THERMAL REGULATION 741 00:37:40,794 --> 00:37:41,928 OR THIRST WHERE YOU DON'T HAVE 742 00:37:41,928 --> 00:37:43,196 WATER YOU DIE. 743 00:37:43,196 --> 00:37:44,798 YOU DON'T DIE IMMEDIATELY. 744 00:37:44,798 --> 00:37:47,467 IT HAS HEALTH CONSEQUENCES BUT 745 00:37:47,467 --> 00:37:57,877 WHY DO I EVEN THINK SOCIAL HOME 746 00:37:57,877 --> 00:37:58,278 KWL 747 00:37:58,278 --> 00:38:02,082 -- HOMEOSTASIS THING AND 748 00:38:02,082 --> 00:38:03,950 THERE'S NEURONS IN THE DORSAL 749 00:38:03,950 --> 00:38:06,653 NUCLEUS THE HOME OF SEROTONIN 750 00:38:06,653 --> 00:38:12,058 NEURONS AND ABOUT 20% DOPAMINE 751 00:38:12,058 --> 00:38:19,199 NEURONS IN THERE AND WE SEE S 752 00:38:19,199 --> 00:38:23,002 SYNAPTIC CONNECTION AND IF WE 753 00:38:23,002 --> 00:38:25,705 ACTIVATE THE NEURONS WE'LL DRIVE 754 00:38:25,705 --> 00:38:29,442 EYE PRO SOCIAL BUT AVERSIVE 755 00:38:29,442 --> 00:38:31,544 BEHAVIORAL STATE AND IF WE 756 00:38:31,544 --> 00:38:33,246 SILENCE THE NEURONS, NOTHING 757 00:38:33,246 --> 00:38:35,081 HAPPENS WHEN THE GROUP IS HOUSED 758 00:38:35,081 --> 00:38:38,618 BUT IF WE PHOTO INHIBIT THE 759 00:38:38,618 --> 00:38:40,520 NEURONS WE BLOCK ISOLATION 760 00:38:40,520 --> 00:38:41,087 INDUCED REBOUND OF SOCIAL 761 00:38:41,087 --> 00:38:48,161 INTERACTION. 762 00:38:48,161 --> 00:38:50,463 INITIALLY THIS WAS CONFUSING AND 763 00:38:50,463 --> 00:38:55,401 WE THINK OF WHAT MAKES US PRO 764 00:38:55,401 --> 00:38:58,138 ASSOCIATION AND WHAT'S IT MEAN 765 00:38:58,138 --> 00:39:01,674 TO BE HAVE A PROSOCIAL WORK 766 00:39:01,674 --> 00:39:02,976 THAT'S AVERSIVE AND FROM OUR 767 00:39:02,976 --> 00:39:05,545 WORK ON VALENCE YOU CAN ENGAGE 768 00:39:05,545 --> 00:39:07,914 TO SEEK PLEASURE OR AVOID PAIN. 769 00:39:07,914 --> 00:39:13,553 YOU CAN SEEK SOCIAL CONTACT FOR 770 00:39:13,553 --> 00:39:15,121 THE SOCIAL REWARDING EXPERIENCE 771 00:39:15,121 --> 00:39:17,924 OR FOR TO AVOID THE UNPLEASANT 772 00:39:17,924 --> 00:39:22,562 STATE OF LONELINESS. 773 00:39:22,562 --> 00:39:27,133 SO THIS IS MEAN STATE MADE US 774 00:39:27,133 --> 00:39:31,104 THINK OF SOCIAL HOMEOSTASIS AS A 775 00:39:31,104 --> 00:39:36,442 STATE AND WAY TO IDENTIFY. 776 00:39:36,442 --> 00:39:38,811 LONELINESS WAS NOT A WORD 777 00:39:38,811 --> 00:39:40,079 PREVIOUSLY USED IN NEURO SCIENCE 778 00:39:40,079 --> 00:39:41,614 AND IT BREAKS DOWN FOUR 779 00:39:41,614 --> 00:39:42,215 CRITERIA. 780 00:39:42,215 --> 00:39:46,019 ONE, IT DRIVES A PROSOCIAL 781 00:39:46,019 --> 00:39:48,888 STATE, TWO, IT'S IN AVERSIVE 782 00:39:48,888 --> 00:39:51,457 UNPLEASANT STATE. 783 00:39:51,457 --> 00:39:52,725 THREE, DISTINCT FROM GENERALIZED 784 00:39:52,725 --> 00:39:54,294 ANXIETY AND FOUR SUBJECTIVE. 785 00:39:54,294 --> 00:39:58,698 MEANING YOU CAN FEEL LONELY AT A 786 00:39:58,698 --> 00:40:03,570 PARTY OR FINE ALONE IN YOUR 787 00:40:03,570 --> 00:40:03,770 ROOM. 788 00:40:03,770 --> 00:40:05,138 MAYBE THIS WOULD HAVE BEEN A 789 00:40:05,138 --> 00:40:06,506 SHOW STOPPER. 790 00:40:06,506 --> 00:40:09,375 HOW DO WE GET TO LONELINESS IN A 791 00:40:09,375 --> 00:40:09,709 MOUSE. 792 00:40:09,709 --> 00:40:12,645 TOUGH ONE BUT ACTUALLY EVERY 793 00:40:12,645 --> 00:40:17,350 SINGLE CAGE FORM A HIERARCHY AND 794 00:40:17,350 --> 00:40:18,885 THE EXPERIENCE OF EACH MOUSE 795 00:40:18,885 --> 00:40:20,320 WOULD BE DIFFERENT. 796 00:40:20,320 --> 00:40:24,390 IF I'M A DOMINANT MOUSE I'M 797 00:40:24,390 --> 00:40:25,758 ENJOYING MY SOCIAL ENVIRONMENT 798 00:40:25,758 --> 00:40:28,461 AND GETTING RESOURCES TO MATE 799 00:40:28,461 --> 00:40:31,798 AND IF I'M A SUBORDINATE I'M A 800 00:40:31,798 --> 00:40:32,699 VICTIM OF VIOLENCE AND 801 00:40:32,699 --> 00:40:34,434 AGGRESSION AND MAYBE I FEEL 802 00:40:34,434 --> 00:40:38,137 GREAT WHEN I'M ISOLATED FROM MY 803 00:40:38,137 --> 00:40:42,208 AGGRESSORS AND THIS WAS THE 804 00:40:42,208 --> 00:40:42,675 QUESTION. 805 00:40:42,675 --> 00:40:45,378 WE FOUND IN ALL THE 806 00:40:45,378 --> 00:40:49,682 MANIPULATIONS WE FOUND A STRONG 807 00:40:49,682 --> 00:40:52,752 CORRELATION WITH SOCIAL RANK AND 808 00:40:52,752 --> 00:40:54,621 MANIPULATING THESE IN 809 00:40:54,621 --> 00:40:55,455 SUBORDINATES DOESN'T DO ANYTHING 810 00:40:55,455 --> 00:40:59,592 THE ONLY TIME WE GET AN EFFECT 811 00:40:59,592 --> 00:41:01,160 IS IN MORE DOMINANT ANIMALS. 812 00:41:01,160 --> 00:41:04,564 WE'RE BEGINNING TO THINK OF THE 813 00:41:04,564 --> 00:41:06,666 NEURONS AS CONTRIBUTING TO IT AN 814 00:41:06,666 --> 00:41:15,108 ER SYSTEM -- EFFECTER SYSTEMS 815 00:41:15,108 --> 00:41:16,943 AND CORRECTS THE DEFICIT AND 816 00:41:16,943 --> 00:41:17,810 IMPORTANT OR THE RELEVANCE OF 817 00:41:17,810 --> 00:41:20,246 THE WORK WE HAVE THE RARE 818 00:41:20,246 --> 00:41:25,385 OPPORTUNITY TO REPLICATE THE 819 00:41:25,385 --> 00:41:35,662 STUDY IN HUMANS. 820 00:41:39,599 --> 00:41:41,401 EVEN 10 HOURS OF ISOLATION WAS 821 00:41:41,401 --> 00:41:45,638 ENOUGH TO EVOKE AN AUGMENTED 822 00:41:45,638 --> 00:41:49,208 SIGNAL WHEN EXPOSED TO SOCIAL 823 00:41:49,208 --> 00:41:49,442 STIMULI. 824 00:41:49,442 --> 00:41:51,377 SO BACK TO OUR KEY WORK HERE. 825 00:41:51,377 --> 00:41:55,181 WE HAVE TO FIGURE OUT THE 826 00:41:55,181 --> 00:41:55,548 CIRCUIT. 827 00:41:55,548 --> 00:41:57,350 IT'S EXCITING TO HAVE IDENTIFIED 828 00:41:57,350 --> 00:41:58,918 THE CELL TYPE THAT CAN BE PART 829 00:41:58,918 --> 00:42:00,586 OF THE EFFECTER SYSTEM. 830 00:42:00,586 --> 00:42:03,690 BECAUSE THEN WE CAN TRACE IT 831 00:42:03,690 --> 00:42:06,192 UPSTREAM AND FIND THE CONTROL 832 00:42:06,192 --> 00:42:07,960 SYSTEM WHICH MUST RECEIVE INPUT 833 00:42:07,960 --> 00:42:09,395 THERE A VERY DISTRIBUTED 834 00:42:09,395 --> 00:42:10,530 DETECTER SYSTEM. 835 00:42:10,530 --> 00:42:18,404 THIS IS NOT GOING TO BE LIKE 836 00:42:18,404 --> 00:42:19,906 DETECTING THINGS BUT IT'S MEMORY 837 00:42:19,906 --> 00:42:22,942 SYSTEMS AND ALL THE MODALITIES 838 00:42:22,942 --> 00:42:27,313 AND THE SOCIAL CONTACT IS HIGHLY 839 00:42:27,313 --> 00:42:28,614 NON TRIVIAL AND I'LL COMPANY 840 00:42:28,614 --> 00:42:29,449 BACK TO THIS. 841 00:42:29,449 --> 00:42:33,319 ANOTHER NODE I PROPOSE WE NEED 842 00:42:33,319 --> 00:42:38,024 IN THE HOMOSTATIC SYSTEM 843 00:42:38,024 --> 00:42:39,592 REPRESENTS SOCIAL RANK AND THIS 844 00:42:39,592 --> 00:42:41,260 NODE MUST BE ABLE TO SUPPRESS 845 00:42:41,260 --> 00:42:42,995 THE EFFECTER SYSTEM OR MODULATE 846 00:42:42,995 --> 00:42:47,800 THE CONTROL CENTER SET POINT. 847 00:42:47,800 --> 00:42:53,639 IF I'M A SUBORDINATE MALE I WANT 848 00:42:53,639 --> 00:42:57,777 TO MINGLE WITH THESAL AS IF BUT 849 00:42:57,777 --> 00:43:01,514 DON'T WANT TO GET BEAT UP SO 850 00:43:01,514 --> 00:43:02,849 SUPPRESS MY EFFECTER DRIVE. 851 00:43:02,849 --> 00:43:05,051 ONE OF THE BIGGEST CHALLENGES 852 00:43:05,051 --> 00:43:07,420 AND WE MENTIONED TECHNICAL 853 00:43:07,420 --> 00:43:07,720 CHALLENGES. 854 00:43:07,720 --> 00:43:11,324 ONE OF THE BIGGEST IS MEASURING 855 00:43:11,324 --> 00:43:12,558 THE ENVIRONMENT. 856 00:43:12,558 --> 00:43:13,826 WHAT IS THE ENVIRONMENT? 857 00:43:13,826 --> 00:43:18,264 IT'S NOT JUST PUTTING OUT THE 858 00:43:18,264 --> 00:43:20,967 THERMOMETER AND MEASURING THE 859 00:43:20,967 --> 00:43:22,235 SOCIAL ENVIRONMENT IS 860 00:43:22,235 --> 00:43:23,536 COMPLICATED SO I'LL TALK ABOUT 861 00:43:23,536 --> 00:43:24,804 THE PIPELINE WE DEVELOPED TO 862 00:43:24,804 --> 00:43:26,072 DEVELOP THAT. 863 00:43:26,072 --> 00:43:31,144 WHAT WE KNOW SO FAR AND A 864 00:43:31,144 --> 00:43:41,621 MENTION THE AND LOOK AT THE 865 00:43:43,656 --> 00:43:49,228 STATE AVERSION BY DISTINCT 866 00:43:49,228 --> 00:43:49,929 PROJECTIONS. 867 00:43:49,929 --> 00:43:54,400 WE CAN TRACE BACKWARDS USING 868 00:43:54,400 --> 00:43:56,803 TECHNOLOGY DEVELOPED AND WE CAN 869 00:43:56,803 --> 00:43:59,772 LOOK AT FIND A SHORT LIST OF 870 00:43:59,772 --> 00:44:01,908 CANDIDATES THAT COULD BE THIS 871 00:44:01,908 --> 00:44:03,176 POTENTIAL CONTROL CENTER. 872 00:44:03,176 --> 00:44:05,778 AND WORK FROM MY VERY FIRST 873 00:44:05,778 --> 00:44:09,582 GRADUATE STUDENT NOW FACULTY AT 874 00:44:09,582 --> 00:44:12,251 UVA AND IS HERE TODAY. 875 00:44:12,251 --> 00:44:14,754 EDWARD FOUND IN HIS THESIS WORK 876 00:44:14,754 --> 00:44:18,691 WITH ME IF YOU STIPULATE THE 877 00:44:18,691 --> 00:44:29,702 GAGA -- GA BERRER ERGIC NEURON 878 00:44:35,508 --> 00:44:39,545 GET A TYPE AND A LAB AT YALE 879 00:44:39,545 --> 00:44:41,614 FUND THE LOOP IS VERY IMPORTANT 880 00:44:41,614 --> 00:44:43,182 FOR AL LEARNING. 881 00:44:43,182 --> 00:44:48,988 THE INTERIOR SINGULAR CORTEX 882 00:44:48,988 --> 00:44:50,690 IMPORTANT FOR EXTRACTING 883 00:44:50,690 --> 00:44:52,425 INFORMATION THERE AN AGENT AND 884 00:44:52,425 --> 00:44:56,229 FEEDING THAT FORWARD WHERE 885 00:44:56,229 --> 00:45:06,572 LEARNING CAN HAPPEN. 886 00:45:07,106 --> 00:45:08,908 AND A FORMER FACULTY UNIT AT 887 00:45:08,908 --> 00:45:10,843 FLORIDA FOLLOWING UP ON WORK IN 888 00:45:10,843 --> 00:45:17,517 HUMANS AND RODENTS IMPLICATING 889 00:45:17,517 --> 00:45:22,822 THE PFC IS IMPORTANT FOR SOCIAL 890 00:45:22,822 --> 00:45:25,291 RANK AND CAN PREDICT COMPETITIVE 891 00:45:25,291 --> 00:45:27,360 SUCCESS LONG BEFORE IT OCCURS. 892 00:45:27,360 --> 00:45:29,562 AND BEFORE THE OVER ALL 893 00:45:29,562 --> 00:45:31,631 STRUCTURE FIGURING OUT THE WHOLE 894 00:45:31,631 --> 00:45:36,936 CIRCUIT, NANCY FOUND THE PFC 895 00:45:36,936 --> 00:45:39,672 PROJECTION SPECIFICALLY AND NOT 896 00:45:39,672 --> 00:45:45,177 THE PROJECTION TO THE PLA IS 897 00:45:45,177 --> 00:45:47,547 IMPORTANT FOR DRIVING DOMINANCE 898 00:45:47,547 --> 00:45:50,082 BEHAVIOR. 899 00:45:50,082 --> 00:45:54,554 NOW THAT SKELETAL MAP WE CAN 900 00:45:54,554 --> 00:45:56,222 THINK OF THE DYNAMICS MUCH THIS. 901 00:45:56,222 --> 00:45:59,659 WE'RE STILL THINKING ABOUT THE 902 00:45:59,659 --> 00:46:01,127 INDIVIDUAL RESPONSE TO SOCIAL 903 00:46:01,127 --> 00:46:05,665 CONTACT HERE BUT IF YOU LOOK AT 904 00:46:05,665 --> 00:46:09,936 THE LITERATURE WITH ACUTE 905 00:46:09,936 --> 00:46:16,742 ISOLATION WHEN YOU REINTRODUCE 906 00:46:16,742 --> 00:46:19,145 ANIMAL TO THE GROUP THERE'S A 907 00:46:19,145 --> 00:46:20,713 PROSOCIAL RESPONSE BUT WITH 908 00:46:20,713 --> 00:46:23,115 CHRONIC SOCIAL ISOLATION YOU GET 909 00:46:23,115 --> 00:46:24,817 SOMETHING VERY DIFFERENT. 910 00:46:24,817 --> 00:46:29,288 YOU GET AGGRESSIVE TERRITORIAL, 911 00:46:29,288 --> 00:46:33,359 ANTITERRITORIAL AVOIDANT 912 00:46:33,359 --> 00:46:33,626 BEHAVIOR. 913 00:46:33,626 --> 00:46:36,762 HOW ARE WE GIVING THE SAME 914 00:46:36,762 --> 00:46:38,064 MANIPULATION, SOCIAL ISOLATION 915 00:46:38,064 --> 00:46:39,899 AND REINTRODUCTION IN THE SOCIAL 916 00:46:39,899 --> 00:46:42,768 GROUP AND GETTING OPPOSITE 917 00:46:42,768 --> 00:46:44,570 VALENCES? 918 00:46:44,570 --> 00:46:48,441 THIS IS THE MODEL OF SOCIAL 919 00:46:48,441 --> 00:46:50,142 HOMEOSTASIS WHEN WE FIRST PUT 920 00:46:50,142 --> 00:46:53,145 THIS OUT CONCEPTUAL BASED ON 921 00:46:53,145 --> 00:46:55,815 JUST IDEAS AND WEIGHT TO BE 922 00:46:55,815 --> 00:46:57,083 PROVEN WRONG. 923 00:46:57,083 --> 00:47:02,521 I INVITE EVERYONE TO JOIN THE 924 00:47:02,521 --> 00:47:07,059 CHARGE HERE. 925 00:47:07,059 --> 00:47:14,200 WE HAVE THE TERM OF QUALITY AND 926 00:47:14,200 --> 00:47:15,868 QUANTITY AND AT SOME POINT IF WE 927 00:47:15,868 --> 00:47:18,604 BECOME SOCIALLY ISOLATED WHAT 928 00:47:18,604 --> 00:47:20,306 WE'RE DETECTING DEVIATES FROM 929 00:47:20,306 --> 00:47:21,741 THE SET POINT ARE EFFECTER 930 00:47:21,741 --> 00:47:24,577 SYSTEM MAY BE ACTIVATED, MAYBE 931 00:47:24,577 --> 00:47:27,980 I'LL CALL AND TALK TO MY FRIEND 932 00:47:27,980 --> 00:47:32,451 OR IF I'M A MOUSE I MAKE ULTRA 933 00:47:32,451 --> 00:47:35,354 SONIC SOCIALIZATION AND THEN 934 00:47:35,354 --> 00:47:37,490 SOCIAL HOMEOSTASIS IS MAINTAINS. 935 00:47:37,490 --> 00:47:39,959 SOMETIMES YOU'RE SOCIALLY 936 00:47:39,959 --> 00:47:41,927 ISOLATED AND YOU'RE MAKE ULTRA 937 00:47:41,927 --> 00:47:44,597 SONIC VOCALIZATION AND CALLING 938 00:47:44,597 --> 00:47:46,999 YOUR FRIENDS BUT MAYBE YOUR 939 00:47:46,999 --> 00:47:49,201 ENTIRE COLONY GOT EATEN BY A 940 00:47:49,201 --> 00:47:50,703 PREDATOR OR THERE'S A GLOBAL 941 00:47:50,703 --> 00:47:51,270 PANDEMIC. 942 00:47:51,270 --> 00:47:53,172 WHAT WE OBSERVED IS THERE SEEMS 943 00:47:53,172 --> 00:47:57,043 TO BE A MERE SET FUNCTION LIKE 944 00:47:57,043 --> 00:47:58,577 DROP OF CORRECTION EFFORTS MADE. 945 00:47:58,577 --> 00:48:00,446 YOU CALL, YOU CALL UNTIL YOU 946 00:48:00,446 --> 00:48:01,414 STOP CALLING. 947 00:48:01,414 --> 00:48:03,849 YOU GO OUT AND TRY UNTIL YOU 948 00:48:03,849 --> 00:48:06,419 JUST STOP GOING OUT AND DON'T 949 00:48:06,419 --> 00:48:08,421 WANT TO LEAVE ANY MORE. 950 00:48:08,421 --> 00:48:10,222 WE'RE SPECULATING THERE'S A SET 951 00:48:10,222 --> 00:48:11,924 POINT ADAPTATION AT THIS POINT 952 00:48:11,924 --> 00:48:13,359 AFTER WHICH WHEN YOU BRING YOUR 953 00:48:13,359 --> 00:48:15,861 SET POINT DOWN TO YOUR NEW 954 00:48:15,861 --> 00:48:18,464 NORMAL, WHEN YOU ARE 955 00:48:18,464 --> 00:48:21,167 RE-INTRODUCED TO OUR SOCIAL 956 00:48:21,167 --> 00:48:23,636 GROUP, YOUR PREVIOUS OPTIMUM NOW 957 00:48:23,636 --> 00:48:25,838 FEELS LIKE A SURPLUS. 958 00:48:25,838 --> 00:48:29,608 SO SORRY THIS ANIMATION ALSO GOT 959 00:48:29,608 --> 00:48:31,944 BOTCHED BUT THE SAME Y AXIS OR 960 00:48:31,944 --> 00:48:34,246 HERE IS SOMETHING WE WANT TO DIG 961 00:48:34,246 --> 00:48:35,848 INTO THE QUALITY AND QUANTITY OF 962 00:48:35,848 --> 00:48:37,917 SOCIAL CONTACT. 963 00:48:37,917 --> 00:48:40,352 WHEN WE THINK OF SOCIAL UTILITY, 964 00:48:40,352 --> 00:48:41,654 THERE'S THE QUANTITY WHICH YOU 965 00:48:41,654 --> 00:48:45,758 CAN BE ISOLATED, YOU CAN BE OVER 966 00:48:45,758 --> 00:48:46,292 CROWDED. 967 00:48:46,292 --> 00:48:49,228 THERE'S A JUST RIGHT OPTIMUM 968 00:48:49,228 --> 00:48:57,403 WHEREAS THE QUALITY IS MO 969 00:48:57,403 --> 00:48:58,571 MONOTOMMICALLY MOVINGUP WARD AND 970 00:48:58,571 --> 00:49:03,709 WE WANTED TO THINK ABOUT SOCIAL 971 00:49:03,709 --> 00:49:09,148 ISOLATION AND ALSO SOCIAL 972 00:49:09,148 --> 00:49:17,757 EXCLUSION. 973 00:49:17,757 --> 00:49:20,860 SOCIAL ISOLATION INCREASES 974 00:49:20,860 --> 00:49:23,195 ANXIETY AND DEPRESSION AND IN 975 00:49:23,195 --> 00:49:26,866 HUMANS EVEN PERCEIVED LONELINESS 976 00:49:26,866 --> 00:49:36,275 CAN INCREASE THE MORBIDITY OF 977 00:49:36,275 --> 00:49:39,712 HEART DISEASE AND SIT THE 978 00:49:39,712 --> 00:49:42,481 EFFECTER SYSTEM ACTIVATION AND 979 00:49:42,481 --> 00:49:43,516 WE'D MAKE DIFFERENT HEALTH 980 00:49:43,516 --> 00:49:45,217 RECOMMENDATIONS BASED ON THAT 981 00:49:45,217 --> 00:49:45,518 KNOWLEDGE. 982 00:49:45,518 --> 00:49:47,787 WE WANTED TO STUDY THIS. 983 00:49:47,787 --> 00:49:49,188 APOLOGIES FOR THE TIME SCALES. 984 00:49:49,188 --> 00:49:51,323 THIS IS WARPED BUT WE WANT TO 985 00:49:51,323 --> 00:49:52,391 EXPLORE THE TIME COURSE OF 986 00:49:52,391 --> 00:49:54,794 SOCIAL ISOLATION TO TRY TO 987 00:49:54,794 --> 00:50:03,936 IDENTIFY WHICH KEY POINT IS THE 988 00:50:03,936 --> 00:50:14,113 UNDER PINNINGS AND 14 DAYS IS 989 00:50:14,113 --> 00:50:16,115 THE TIME POINT THAT PRODUCES 990 00:50:16,115 --> 00:50:18,083 AGGRESSIVE BEHAVIOR. 991 00:50:18,083 --> 00:50:23,189 WE WANTED TO EXPLORE THIS AND 992 00:50:23,189 --> 00:50:25,591 ANIMALS ISOLATED FOR DIFFERENT 993 00:50:25,591 --> 00:50:25,858 PERIODS. 994 00:50:25,858 --> 00:50:28,727 LOTS OF GROUPS AND LOST WORK AND 995 00:50:28,727 --> 00:50:33,399 THEN WE REINTRODUCED ANIMALS TO 996 00:50:33,399 --> 00:50:34,133 A JUVENILE. 997 00:50:34,133 --> 00:50:36,869 WHAT CHRISTOPHER LEE AND MY LAB 998 00:50:36,869 --> 00:50:38,704 HAS FOUND INDEED THAT BASICALLY 999 00:50:38,704 --> 00:50:41,373 WE'RE KIND OF RIGHT. 1000 00:50:41,373 --> 00:50:43,642 THERE DOES SEEM TO BE THIS 1001 00:50:43,642 --> 00:50:45,678 IMMEDIATE INCREASE IN PROSOCIAL 1002 00:50:45,678 --> 00:50:47,780 BEHAVIOR THAT KIND OF COMES BACK 1003 00:50:47,780 --> 00:50:50,216 DOWN AND AT 14 AND 28 DAYS WE'RE 1004 00:50:50,216 --> 00:50:51,984 BACK DOWN TO BASELINE AGAIN AND 1005 00:50:51,984 --> 00:50:54,620 ALSO I WANT TO POINT OUT AT 1006 00:50:54,620 --> 00:50:55,888 SEVEN DAYS WE'RE GETTING A LOT 1007 00:50:55,888 --> 00:50:57,189 OF VARIABILITY SO THAT'S 1008 00:50:57,189 --> 00:50:58,357 SOMETHING TO THINK ABOUT TOO HOW 1009 00:50:58,357 --> 00:50:58,924 DIFFERENT INDIVIDUALS WILL 1010 00:50:58,924 --> 00:51:05,698 RESPOND. 1011 00:51:05,698 --> 00:51:11,103 NOT ALL INTERACTIONS ARE THE 1012 00:51:11,103 --> 00:51:13,105 SAME WAY AND IT'S A CRUDE WAY TO 1013 00:51:13,105 --> 00:51:15,774 LOOK AT SOCIAL BEHAVIOR AND 1014 00:51:15,774 --> 00:51:17,376 WANTED TO GET MORE QUANTITATIVE 1015 00:51:17,376 --> 00:51:20,512 AND MAKE STUDYING THIS BEHAVIOR 1016 00:51:20,512 --> 00:51:22,348 A QUANTITATIVE AND RIGOROUS 1017 00:51:22,348 --> 00:51:22,615 PURSUIT. 1018 00:51:22,615 --> 00:51:25,451 WE BEGAN WITH POST TRACKING AND 1019 00:51:25,451 --> 00:51:27,753 USING A FLEXIBLE CUSTOM PIPELINE 1020 00:51:27,753 --> 00:51:29,622 WE CAN SELECT FOR SECOND AND 1021 00:51:29,622 --> 00:51:30,756 THIRD ORDER FEATURES. 1022 00:51:30,756 --> 00:51:32,191 HAPPY TO TAKE QUESTIONS ABOUT 1023 00:51:32,191 --> 00:51:37,029 THIS AT THE END, TO PUT IN AND 1024 00:51:37,029 --> 00:51:41,233 PERFORM DIMENSIONALITY REDUCTION 1025 00:51:41,233 --> 00:51:42,601 AND CLUSTERING. 1026 00:51:42,601 --> 00:51:51,143 WE HAVE VARYIIATIONS AND 90% OF 1027 00:51:51,143 --> 00:51:53,345 THE DATA I CAN'T SHOW TODAY BUT 1028 00:51:53,345 --> 00:51:57,349 AFTER 24 HOURS THE RECORDING IN 1029 00:51:57,349 --> 00:51:59,218 THE PREFRONTAL CORTEX SHOW A 1030 00:51:59,218 --> 00:52:01,487 LONGER TRAJECTORY. 1031 00:52:01,487 --> 00:52:04,757 THE IMMEDIATE EFFECTS ARE NOT 1032 00:52:04,757 --> 00:52:06,258 OFFENSE AND NOTHING'S JUMPING 1033 00:52:06,258 --> 00:52:08,294 OUT BUT THE POPULATION DYNAMICS 1034 00:52:08,294 --> 00:52:10,696 ARE EXPAND AT 24 HOURS EVEN 1035 00:52:10,696 --> 00:52:11,330 THOUGH THEY'RE REPRESENTING THE 1036 00:52:11,330 --> 00:52:21,573 SAME FEATURES. 1037 00:52:22,141 --> 00:52:23,642 BACK TO THIS QUESTION -- I WANT 1038 00:52:23,642 --> 00:52:26,478 TO FOCUS ON THE QUALITY. 1039 00:52:26,478 --> 00:52:29,348 A COUPLE YEARS IN MY PIONEER 1040 00:52:29,348 --> 00:52:31,317 WORK I TOUCHED BASE WITH WEN AND 1041 00:52:31,317 --> 00:52:32,885 SHE SAID THAT'S COOL. 1042 00:52:32,885 --> 00:52:34,887 SOUNDS LIKE YOU'RE MAKING 1043 00:52:34,887 --> 00:52:39,124 PERFECTING BUT YOU SHOULD STUDY 1044 00:52:39,124 --> 00:52:39,425 PAIN. 1045 00:52:39,425 --> 00:52:44,430 I WAS LIKE, I DON'T STUDY PAIN. 1046 00:52:44,430 --> 00:52:51,804 IT'S SO FAR FROM WHAT I WORK ON 1047 00:52:51,804 --> 00:52:56,175 BUT BEING PART OF THIS 1048 00:52:56,175 --> 00:52:57,209 INCREDIBLE COMMUNITY NCCIH I 1049 00:52:57,209 --> 00:53:02,915 THOUGHT OF MYSELF AS AN OUT OF 1050 00:53:02,915 --> 00:53:09,188 THE BOX RESEARCH EVER -- 1051 00:53:09,188 --> 00:53:15,260 RESEARCHER AND THE PAIN OVERLAP 1052 00:53:15,260 --> 00:53:19,231 THEORY SUGGESTS AND IS BASED ON 1053 00:53:19,231 --> 00:53:20,799 A LOT OF THINGS BUT A LOT OF 1054 00:53:20,799 --> 00:53:21,834 OBSERVATIONS INCLUDING THESE 1055 00:53:21,834 --> 00:53:25,371 IMAGING STUDIES IN HUMANS 1056 00:53:25,371 --> 00:53:29,074 SHOWING SIMILAR BRAIN REGIONS 1057 00:53:29,074 --> 00:53:39,618 AND WHOLE FMRI WITH THE INTERIOR 1058 00:53:40,252 --> 00:53:42,287 INSULAR CORTEX IMPORTANT FOR 1059 00:53:42,287 --> 00:53:44,423 DETECTING THE INTERNAL STATE OF 1060 00:53:44,423 --> 00:53:48,994 ORGANS AND SELF-AWARENESS AND 1061 00:53:48,994 --> 00:53:51,797 EMOTIONAL AWARENESS AS CRAIG PUT 1062 00:53:51,797 --> 00:53:52,664 IT AND ALSO SOCIAL AND PHYSICAL 1063 00:53:52,664 --> 00:53:55,367 PAIN. 1064 00:53:55,367 --> 00:54:00,439 SO HOW DO WE GET AT THIS? 1065 00:54:00,439 --> 00:54:04,176 MY STUDENT DEVELOPED WHAT WE 1066 00:54:04,176 --> 00:54:07,446 CALL THE FOMO AND IT STANDS FOR 1067 00:54:07,446 --> 00:54:11,717 FEAR OF MISSING OUT AND IT COMES 1068 00:54:11,717 --> 00:54:21,627 FROM THIS PHENOMENON AND YOU 1069 00:54:21,627 --> 00:54:23,695 CHECK SOCIAL MEDIA AND WONDERING 1070 00:54:23,695 --> 00:54:25,964 WHAT THEY'RE DOING AND WANT TO 1071 00:54:25,964 --> 00:54:28,067 GET AT THIS. 1072 00:54:28,067 --> 00:54:30,369 WE USED A REAL TIME OBJECT 1073 00:54:30,369 --> 00:54:32,905 DETECTION TOOL AND YOU CAN SEE 1074 00:54:32,905 --> 00:54:34,773 WHAT'S HAPPENING HERE ALL FOUR 1075 00:54:34,773 --> 00:54:36,208 ANIMALS HAVE BEEN TRAINED THAT A 1076 00:54:36,208 --> 00:54:40,479 CUE PREDICTS REWARD DELIVERY AT 1077 00:54:40,479 --> 00:54:42,614 THIS MILK SHAKE FOUNTAIN AND ALL 1078 00:54:42,614 --> 00:54:44,249 LEARNED SEPARATELY ON THEIR OWN 1079 00:54:44,249 --> 00:54:46,618 AND THEN ONE OF THE MICE GETS 1080 00:54:46,618 --> 00:54:48,854 INCLUDED AND YOU CAN SEE THE 1081 00:54:48,854 --> 00:54:50,923 VARIATIONS OF BEHAVIOR. 1082 00:54:50,923 --> 00:54:55,260 SOMETIMES WHEN THE PURPLE DOT 1083 00:54:55,260 --> 00:54:56,662 WAS APPEARING THEY'RE EXHIBITING 1084 00:54:56,662 --> 00:54:57,930 FOMO AND SOMETIMES FINE. 1085 00:54:57,930 --> 00:55:00,833 NOT ATTENDING AND NOT GIVING 1086 00:55:00,833 --> 00:55:03,502 BONDY LANGUAGE THEY'RE ATTENDING 1087 00:55:03,502 --> 00:55:08,941 TO THE -- BODY LANGUAGE THEY'RE 1088 00:55:08,941 --> 00:55:10,008 ATTENDING THE SBPGS HOW 1089 00:55:12,644 --> 00:55:14,713 AND ALL THE FRAMES ARE SORTED BY 1090 00:55:14,713 --> 00:55:16,448 THE CLUSTER. 1091 00:55:16,448 --> 00:55:20,853 TO SHOW HOW SIMILAR AND VARIABLE 1092 00:55:20,853 --> 00:55:22,154 THE FRAMES ARE WITHIN THE 1093 00:55:22,154 --> 00:55:30,095 CLUSTER AND BETWEEN CLUSTERS. 1094 00:55:30,095 --> 00:55:32,931 AND NOW THE SAME VIDEO 1095 00:55:32,931 --> 00:55:35,901 CHRONOLOGICALLY FROM THE 1096 00:55:35,901 --> 00:55:37,769 BEGINNING AND EVERY FRAME HAS 1097 00:55:37,769 --> 00:55:39,505 BEEN ASSIGNED A FUNCTIONAL 1098 00:55:39,505 --> 00:55:41,473 CLUSTER ALLOWING US TO ACHIEVE A 1099 00:55:41,473 --> 00:55:43,175 TIME STAMP FOR EVERY SINGLE 1100 00:55:43,175 --> 00:55:45,043 BEHAVIOR THOUGH THERE IS A TRIAL 1101 00:55:45,043 --> 00:55:47,179 STRUCTURE THE BEHAVIORS ARE 1102 00:55:47,179 --> 00:55:48,447 CLEARLY ECOLOGICAL AND EVERY 1103 00:55:48,447 --> 00:55:50,415 TRIAL IS DIFFERENT FROM THE 1104 00:55:50,415 --> 00:55:50,849 LAST. 1105 00:55:50,849 --> 00:55:55,254 SO WE'VE GOT THE TASK. 1106 00:55:55,254 --> 00:55:59,391 NOW I'VE SHOWED THE SOCIAL 1107 00:55:59,391 --> 00:56:00,792 EXCLUSION AND CONTROL WHERE 1108 00:56:00,792 --> 00:56:01,660 THERE'S ONLY ONE MOUSE ON THE 1109 00:56:01,660 --> 00:56:02,361 OTHER SIDE. 1110 00:56:02,361 --> 00:56:04,329 THIS IS CONTROL FOR SOCIAL 1111 00:56:04,329 --> 00:56:05,497 EXCLUSION AND STILL ONE MOUSE 1112 00:56:05,497 --> 00:56:07,933 AND THE ANIMAL COULD STILL 1113 00:56:07,933 --> 00:56:09,334 POTENTIALLY EXPERIENCE QUOTE, 1114 00:56:09,334 --> 00:56:13,071 UNQUOTE, ENVY OR THE EXPERIENCE 1115 00:56:13,071 --> 00:56:15,507 OF WATCHING ANOTHER ANIMAL GET 1116 00:56:15,507 --> 00:56:19,044 THE REWARD THEY WANT THEN WE 1117 00:56:19,044 --> 00:56:21,180 HAVE A TONES ONLY CONTROL AND 1118 00:56:21,180 --> 00:56:23,248 THE MILK SHAKE IS DELIVERED AND 1119 00:56:23,248 --> 00:56:26,118 IT'S JUST BEING WASTED AND MAYBE 1120 00:56:26,118 --> 00:56:27,686 THAT'S SAD. 1121 00:56:27,686 --> 00:56:30,088 I'M SO SAD THE DINNER'S BEING 1122 00:56:30,088 --> 00:56:30,322 WASTED. 1123 00:56:30,322 --> 00:56:31,924 WE PUT THEM ON THE HOT PLATE AND 1124 00:56:31,924 --> 00:56:33,525 LOOK AT THE PHYSICAL PAIN 1125 00:56:33,525 --> 00:56:33,792 RESPONSES. 1126 00:56:33,792 --> 00:56:37,329 AND WHAT WE SEE IS ANIMAL THAT 1127 00:56:37,329 --> 00:56:38,263 UNDERWENT THE SOCIAL EXCLUSION 1128 00:56:38,263 --> 00:56:40,632 PARADIGM SHOWED A SIGNIFICANTLY 1129 00:56:40,632 --> 00:56:42,768 HIGHER RESPONSE TO PHYSICAL PAIN 1130 00:56:42,768 --> 00:56:45,337 IN TERMS OF THE LICKING OF THE 1131 00:56:45,337 --> 00:56:47,906 PAW RELATIVE TO ANIMALS THAT 1132 00:56:47,906 --> 00:56:51,543 UNDERWENT THE TONES ONLY 1133 00:56:51,543 --> 00:56:52,277 RESPONSE OR CONDITION. 1134 00:56:52,277 --> 00:56:53,111 WHAT'S GOING ON? 1135 00:56:53,111 --> 00:56:56,448 WHEN HAVE YOU PHYSICAL PAIN AND 1136 00:56:56,448 --> 00:56:59,318 SOCIAL PAIN ARE THEY SYNAPSING 1137 00:56:59,318 --> 00:57:02,554 ON THE SAME CELL WHICH IS A 1138 00:57:02,554 --> 00:57:06,491 POPULAR IDEA WHEN THE PAIN 1139 00:57:06,491 --> 00:57:06,925 OVERLAP THEORY. 1140 00:57:06,925 --> 00:57:09,962 IS THERE A CELLULAR OR SPATIAL 1141 00:57:09,962 --> 00:57:17,002 CONVERGENCE OR WOULD THERE BE 1142 00:57:17,002 --> 00:57:21,940 SIGNALS THAT HELP CREATE THIS 1143 00:57:21,940 --> 00:57:25,844 ADDITIVE AMPLIFICATION OF SOCIAL 1144 00:57:25,844 --> 00:57:27,879 PAIN PEOPLE SAY WE RECORDED IN 1145 00:57:27,879 --> 00:57:34,820 THE INTERIOR INSULAR COVER -- 1146 00:57:34,820 --> 00:57:39,491 CORTEX AND THIS IS A BUSY SLIDE. 1147 00:57:39,491 --> 00:57:49,768 IT'S FUNCTIONALLY CLUSTER ED MAS 1148 00:57:49,768 --> 00:57:54,139 FOR THE FOMO STUDY AND 1149 00:57:54,139 --> 00:57:55,474 CO-REGISTERED THE NEURONS AND 1150 00:57:55,474 --> 00:57:57,142 LONG STORY SHORT IT'S KIND OF A 1151 00:57:57,142 --> 00:57:59,011 HOT MESS, DON'T REALLY SEE 1152 00:57:59,011 --> 00:58:00,445 ANYTHING AND DOESN'T SEEM LIKE 1153 00:58:00,445 --> 00:58:02,948 THE NAME NEURONS INVOLVED IN 1154 00:58:02,948 --> 00:58:04,016 SOCIAL PAIN ARE INVOLVED IN 1155 00:58:04,016 --> 00:58:05,684 PHYSICAL PAIN SO WE'RE GOING 1156 00:58:05,684 --> 00:58:09,087 MOVE ONWARDS TO THE OTHER MODEL. 1157 00:58:09,087 --> 00:58:18,764 AND WE WONDERED ABOUT DOPAMINE 1158 00:58:18,764 --> 00:58:29,308 AND OXYTOCIN AND THEN LOOKED AT 1159 00:58:33,378 --> 00:58:37,582 CANNABINOIDS AND WE USED THE 1160 00:58:37,582 --> 00:58:38,817 ENDOCANNABINOID SENSE IN THE 1161 00:58:38,817 --> 00:58:41,787 CORTEX AND PERFORMED THIS IN THE 1162 00:58:41,787 --> 00:58:42,921 SOCIAL EXCLUSION TASK. 1163 00:58:42,921 --> 00:58:47,759 ON TRIALS WHERE THE ANIMAL WAS A 1164 00:58:47,759 --> 00:58:51,029 FOMO BEHAVIOR SERVICE FINE 1165 00:58:51,029 --> 00:58:54,466 BEHAVIOR WE SEE INCREASED 1166 00:58:54,466 --> 00:58:55,233 ENDOCANNABINOID SIGNALLING 1167 00:58:55,233 --> 00:58:57,269 WITHIN SUBJECT COMPARISON. 1168 00:58:57,269 --> 00:59:01,340 SO THIS SUGGESTED PERHAPS 1169 00:59:01,340 --> 00:59:03,942 ENDOCANNABINOIDS ARE PRODUCING A 1170 00:59:03,942 --> 00:59:07,379 PROTECTIVE EFFECT FOR FOMO 1171 00:59:07,379 --> 00:59:08,513 DURING SOCIAL EXCLUSION. 1172 00:59:08,513 --> 00:59:10,215 AND FOR THE TONES ONLY MAYBE THE 1173 00:59:10,215 --> 00:59:12,384 OPPOSITE TREND AND WITH THE ONE 1174 00:59:12,384 --> 00:59:13,919 MOUSE CONTROL ALSO NO EFFECT. 1175 00:59:13,919 --> 00:59:16,555 THIS IS A FINDING THAT IS 1176 00:59:16,555 --> 00:59:21,460 SPECIFIC TO SOCIAL EXCLUSION. 1177 00:59:21,460 --> 00:59:24,896 THIS IS MY LAST DATA SLIDE AND 1178 00:59:24,896 --> 00:59:28,033 WANTED TO SEE WHAT HAPPENS WITH 1179 00:59:28,033 --> 00:59:30,001 ENDOCANNABINOID SIGNALLING WITH 1180 00:59:30,001 --> 00:59:31,737 PAINFUL STIMULUS AND THERE'S 1181 00:59:31,737 --> 00:59:33,705 OTHER DATA FOR THE DIFFERENT 1182 00:59:33,705 --> 00:59:36,375 STIMULI AND ESSENTIALLY WE'RE 1183 00:59:36,375 --> 00:59:38,410 SEEING THERE'S AN ELEVATED 1184 00:59:38,410 --> 00:59:40,212 CANNABINOID RESPONSE FOR THE 1185 00:59:40,212 --> 00:59:43,348 TONES ONLY SUGGESTING PERHAPS 1186 00:59:43,348 --> 00:59:46,651 THAT THE ENDOCANNABINOID POOL 1187 00:59:46,651 --> 00:59:49,254 HAS BEEN DEPLETED OR USED UP 1188 00:59:49,254 --> 00:59:50,989 DURING THE SOCIAL EXCLUSION OR 1189 00:59:50,989 --> 00:59:57,162 ONE MOUSE CONDITIONS. 1190 00:59:57,162 --> 00:59:58,363 DEFINITELY UNDER CONSTRUCTION. 1191 00:59:58,363 --> 00:59:59,264 LOTS TO DO. 1192 00:59:59,264 --> 01:00:03,135 THIS IS THE BEGINNING OF THE 1193 01:00:03,135 --> 01:00:05,070 EMBRYONIC FIELD OF HOMEOSTASIS 1194 01:00:05,070 --> 01:00:07,005 AND WE BARELY SCRATCHED THE 1195 01:00:07,005 --> 01:00:09,374 SURFACE AND IN CASE YOU'RE 1196 01:00:09,374 --> 01:00:10,876 WONDERING WHICH POSTERS YOU WANT 1197 01:00:10,876 --> 01:00:17,783 TO GO TO AND WANT TO HEAR I'LL 1198 01:00:17,783 --> 01:00:19,818 BE PRESENTING DURING A TALK OF 1199 01:00:19,818 --> 01:00:21,520 SOCIAL ISOLATION TOMORROW 1200 01:00:21,520 --> 01:00:25,056 AFTERNOON AND WE HAVE POSTERS 1201 01:00:25,056 --> 01:00:27,325 TALKING ABOUT NEUROMODULATION 1202 01:00:27,325 --> 01:00:30,162 AND NEW ARCHITECTURES FOR LONG 1203 01:00:30,162 --> 01:00:32,264 LEARNING AND LONGITUDINAL 1204 01:00:32,264 --> 01:00:34,132 MODULATION OF PFC NEURONS DURING 1205 01:00:34,132 --> 01:00:38,003 ACUTE OR SEVERE STRESS OR MILD 1206 01:00:38,003 --> 01:00:43,942 STRESS FROM A STUDENT FACULTY AT 1207 01:00:43,942 --> 01:00:48,947 UCLA AND IF YOU WANT TO HEAR 1208 01:00:48,947 --> 01:00:50,916 MORE ABOUT THE FOMO. 1209 01:00:50,916 --> 01:00:52,217 AND IF YOU'RE INTERESTED IN ANY 1210 01:00:52,217 --> 01:00:53,885 OF THE WORK YOU HEARD ABOUT 1211 01:00:53,885 --> 01:00:56,354 TODAY, I HOPE YOU'LL REACH OUT 1212 01:00:56,354 --> 01:01:00,625 TO ME TO JOIN OUR TEAM BUT IF 1213 01:01:00,625 --> 01:01:06,731 YOU YOU DON'T WANT TO MOVE OUT 1214 01:01:06,731 --> 01:01:11,169 TO WHERE WE ARE REACH OUT TO 1215 01:01:11,169 --> 01:01:14,506 FORMER TRAINEES AND WE HAVE 1216 01:01:14,506 --> 01:01:15,974 POSTDOCS FOR A FEW MORE MONTHS 1217 01:01:15,974 --> 01:01:17,509 BUT THEY'RE RECRUITING. 1218 01:01:17,509 --> 01:01:22,514 WITH THAT I WANT TO THANK ABOVE 1219 01:01:22,514 --> 01:01:25,250 EVERYTHING NCCIH FOR SUPPORTING 1220 01:01:25,250 --> 01:01:27,319 THIS RESEARCH PROGRAM. 1221 01:01:27,319 --> 01:01:31,156 EVERYONE IN MY LAB, PAST, 1222 01:01:31,156 --> 01:01:32,190 PRESENT AND FUTURE. 1223 01:01:32,190 --> 01:01:33,124 AND COLLABORATORS AND YOU FOR 1224 01:01:33,124 --> 01:01:33,959 YOUR ATTENTION. 1225 01:01:33,959 --> 01:01:44,135 THANK YOU. 1226 01:02:03,388 --> 01:02:04,990 >> WE'RE RUNNING SHORT ON TIME 1227 01:02:04,990 --> 01:02:10,161 BUT WE CAN TAKE ONE QUESTION. 1228 01:02:10,161 --> 01:02:12,731 >> WHEN THINKING OF THE OVERLAP 1229 01:02:12,731 --> 01:02:15,967 BETWEEN PHYSICAL AND SOCIAL PAIN 1230 01:02:15,967 --> 01:02:18,436 HAVE YOU CONSIDERED DIVIDING UP 1231 01:02:18,436 --> 01:02:19,738 SOMATIC VERSUS ADVERSE 1232 01:02:19,738 --> 01:02:21,973 COMPONENTS AND SOCIAL PAIN HAS 1233 01:02:21,973 --> 01:02:25,343 MORE OVERLAP WITH AFFECTIVE PAIN 1234 01:02:25,343 --> 01:02:26,645 OVER SOMATIC PAIN? 1235 01:02:26,645 --> 01:02:27,979 >> GREAT QUESTION. 1236 01:02:27,979 --> 01:02:30,181 WHAT I'M TAKING THAT TO MEAN ARE 1237 01:02:30,181 --> 01:02:31,783 WE THINKING ABOUT THE BEHAVIORAL 1238 01:02:31,783 --> 01:02:33,451 RESPONSES TO PAIN, LICKING THE 1239 01:02:33,451 --> 01:02:37,722 PAW, HOLDING THE PAW AND CRYING 1240 01:02:37,722 --> 01:02:39,724 RATHER THAN THEN THE DETECTION 1241 01:02:39,724 --> 01:02:42,961 OF THE NOCICEPTIVE STIMULUS 1242 01:02:42,961 --> 01:02:43,295 THRESHOLD. 1243 01:02:43,295 --> 01:02:44,429 WE LOOKED AT DIFFERENT MEASURES. 1244 01:02:44,429 --> 01:02:49,000 I WOULD SAY MOST THE MEASURES 1245 01:02:49,000 --> 01:02:50,502 WE'VE SEEN ARE ABOUT THE 1246 01:02:50,502 --> 01:02:51,236 AFFECTIVE RESPONSE. 1247 01:02:51,236 --> 01:02:52,103 SOMETHING THAT LOOKS LIKE IT 1248 01:02:52,103 --> 01:02:55,140 COULD BE AFFECTING DETECTION 1249 01:02:55,140 --> 01:02:56,441 THRESHOLDS AS WELL AS BUT BY AND 1250 01:02:56,441 --> 01:02:59,110 LARGE MOST OF OUR SIGNIFICANT 1251 01:02:59,110 --> 01:03:00,679 AFFECTS ARE WITH THE AFFECTIVE 1252 01:03:00,679 --> 01:03:07,719 COMPONENTS SO YOU'RE RIGHT. 1253 01:03:07,719 --> 01:03:08,019 >> TERRIFIC. 1254 01:03:08,019 --> 01:03:18,263 ONE MORE HAND. 1255 01:03:23,702 --> 01:03:23,935 TERRIFIC. 1256 01:03:23,935 --> 01:03:27,105 NEXT I'D LIKE TO GO AHEAD AND 1257 01:03:27,105 --> 01:03:35,213 INTRODUCE AND WELCOME MY 1258 01:03:35,213 --> 01:03:45,657 EMMELINE EDWARDS AND OLGA 1259 01:03:46,825 --> 01:03:49,327 TJURMINA AND THE PANELISTS AS 1260 01:03:49,327 --> 01:03:50,462 WELL IF YOU CAN COME UP THAT 1261 01:03:50,462 --> 01:04:00,772 WOULD BE TERRIFIC. 1262 01:04:02,707 --> 01:04:05,477 >> I'M THE DIRECTOR OF AT NCCIH 1263 01:04:05,477 --> 01:04:09,914 AND PLEASED TO SERVE AS 1264 01:04:09,914 --> 01:04:11,416 MODERATOR FOR THIS SESSION OF 1265 01:04:11,416 --> 01:04:12,717 YOUNG INVESTIGATORS. 1266 01:04:12,717 --> 01:04:15,186 AS YOU HEARD FROM DR. CHEN, 1267 01:04:15,186 --> 01:04:19,557 THROUGH THE EFFORT OF THE OF THE 1268 01:04:19,557 --> 01:04:24,729 INTEROCEPTION GROUP, WE'VE SEEN 1269 01:04:24,729 --> 01:04:32,937 AN AMAZE IING GROWTH IN THIS FI 1270 01:04:32,937 --> 01:04:34,506 SINCE 2018. 1271 01:04:34,506 --> 01:04:37,509 AND I THINK THIS SESSION REALLY 1272 01:04:37,509 --> 01:04:40,912 IS TO FOCUS ON OUR CAPACITY 1273 01:04:40,912 --> 01:04:43,314 BUILDING EFFORTS AND REALLY 1274 01:04:43,314 --> 01:04:46,117 EMPHASIZE THE WORK OF AN AMAZING 1275 01:04:46,117 --> 01:04:48,653 GROUP OF YOUNG INVESTIGATORS. 1276 01:04:48,653 --> 01:04:53,925 THIS WAS A VERY COMPETITIVE 1277 01:04:53,925 --> 01:04:54,159 PROCESS. 1278 01:04:54,159 --> 01:04:55,593 THE PLANNING COMMITTEE RECEIVED 1279 01:04:55,593 --> 01:04:59,397 120 ABSTRACTS AND OUT OF THOSE, 1280 01:04:59,397 --> 01:05:06,604 ONLY SIX WERE CHOSEN. 1281 01:05:06,604 --> 01:05:09,040 AND THE SELECTION CRITERIA WERE 1282 01:05:09,040 --> 01:05:09,240 STIFF. 1283 01:05:09,240 --> 01:05:10,942 THE STRENGTH OF THE HYPOTHESIS 1284 01:05:10,942 --> 01:05:16,981 AND FINDINGS AND USE OF NOVEL 1285 01:05:16,981 --> 01:05:17,749 TECHNOLOGY AND ALSO THE GROUP 1286 01:05:17,749 --> 01:05:20,852 DID AN AMAZING JOB IN TERMS OF 1287 01:05:20,852 --> 01:05:23,955 HAVING DIVERSE GROUP OF 1288 01:05:23,955 --> 01:05:24,389 PRESENTERS. 1289 01:05:24,389 --> 01:05:26,658 YOU CAN SEE THERE'S GOING TO BE 1290 01:05:26,658 --> 01:05:28,426 GOOD DIVERSITY IN THE ORGAN 1291 01:05:28,426 --> 01:05:30,795 SYSTEMS THAT WILL BE 1292 01:05:30,795 --> 01:05:32,964 REPRESENTED, IN THE TYPE OF 1293 01:05:32,964 --> 01:05:33,832 RESEARCH CLINICAL VERSUS BASIC 1294 01:05:33,832 --> 01:05:35,567 AND THE TOPIC THAT ARE GOING TO 1295 01:05:35,567 --> 01:05:37,902 BE PRESENTED. 1296 01:05:37,902 --> 01:05:40,305 IN ADDITION, THE GROUP ALSO PAID 1297 01:05:40,305 --> 01:05:43,341 ATTENTION TO DIVERSITY AND 1298 01:05:43,341 --> 01:05:47,746 GENDER AND ALSO IN ETHNICITY. 1299 01:05:47,746 --> 01:05:50,014 I THINK WE'RE PRIVILEGED TO HAVE 1300 01:05:50,014 --> 01:05:52,016 A GROUP OF YOUNG INVESTIGATORS 1301 01:05:52,016 --> 01:05:53,785 THAT HAVE A DIFFICULT TASK IN 1302 01:05:53,785 --> 01:05:54,819 FIVE MINUTES THEY'LL HAVE TO NOT 1303 01:05:54,819 --> 01:06:00,525 ONLY TELL YOU ABOUT THEMSELVES 1304 01:06:00,525 --> 01:06:03,094 BUT ALSO BUT EXCITING FINDING. 1305 01:06:03,094 --> 01:06:07,932 I'LL TURN IT OVER TO MY 1306 01:06:07,932 --> 01:06:09,100 COLLEAGUE DR. TJURMINA TO 1307 01:06:09,100 --> 01:06:13,138 INTRODUCE THE INVESTIGATORS. 1308 01:06:13,138 --> 01:06:13,905 >> THANK YOU. 1309 01:06:13,905 --> 01:06:23,047 LET ME INTRODUCE OUR SPEAKERS. 1310 01:06:23,047 --> 01:06:26,151 MIN 1311 01:06:26,151 --> 01:06:34,092 MINEL ARINNEL AND KHALIL RAMADI 1312 01:06:34,092 --> 01:06:38,263 ABOUT DEVICES YOU CAN EAT, 1313 01:06:38,263 --> 01:06:40,932 MICHAEL CARDENAS FROM THE 1314 01:06:40,932 --> 01:06:51,309 UNIVERSITY OF ARIZONA, MAKE AN 1315 01:06:51,309 --> 01:06:54,412 APPROACH-AVOIDANCE CONFLICT TASK 1316 01:06:54,412 --> 01:06:57,015 AND SENEGAL ALFRED MABRY FROM 1317 01:06:57,015 --> 01:06:58,016 CORNELL TALKING ABOUT 1318 01:06:58,016 --> 01:07:03,955 DIFFERENCES IN FUNCTIONAL 1319 01:07:03,955 --> 01:07:09,694 CONNECTIONS AND IMPAIRMENTS IN 1320 01:07:09,694 --> 01:07:14,365 HEART-BASED INTEROCEPTION DURING 1321 01:07:14,365 --> 01:07:18,002 PAR PAR KIVEN SONS DURING STRESS 1322 01:07:18,002 --> 01:07:23,541 AND EXERCISE AND LE ZHANG 1323 01:07:23,541 --> 01:07:28,346 LOOKING AT NEURO-IMMUNE 1324 01:07:28,346 --> 01:07:29,781 INTERACTIONS AND INTEROCEPTION 1325 01:07:29,781 --> 01:07:34,552 IN PRODOME JAM PARKINSON'S 1326 01:07:34,552 --> 01:07:41,626 DISEASE AND THEN JOSÉ HERRERO 1327 01:07:41,626 --> 01:07:46,931 RUBIO LOOKING AT PERSISTENT 1328 01:07:46,931 --> 01:07:48,600 DYSPNEA AND SOME PRESENTERS 1329 01:07:48,600 --> 01:07:48,900 POSTERS. 1330 01:07:48,900 --> 01:07:55,173 AND YOU'LL SEE THE NUMBERS AND 1331 01:07:55,173 --> 01:07:56,741 YOU SEE IT NOW. 1332 01:07:56,741 --> 01:08:01,679 YOU'RE INVITED TO ASK YOUR KE 1333 01:08:01,679 --> 01:08:02,647 QUESTIONS DURING THE POSTER 1334 01:08:02,647 --> 01:08:03,681 SESSION BECAUSE EACH PRESENTER 1335 01:08:03,681 --> 01:08:05,516 HAS ONLY FIVE MINUTES TO PRESENT 1336 01:08:05,516 --> 01:08:09,954 THEIR WORK. 1337 01:08:09,954 --> 01:08:19,597 NOW, PLEASE. 1338 01:08:19,597 --> 01:08:26,604 >> HELLO, I'M A FIFTH YEAR 1339 01:08:26,604 --> 01:08:27,605 STUDENT AT DUKE INVESTIGATION 1340 01:08:27,605 --> 01:08:31,709 AND MAPPING THE GUT BRAIN 1341 01:08:31,709 --> 01:08:32,310 CIRCUITRY TO ANSWER COMPLEX 1342 01:08:32,310 --> 01:08:34,379 BIOLOGICAL QUESTIONS. 1343 01:08:34,379 --> 01:08:37,515 AS SOME OF YOU ALREADY KNOW THE 1344 01:08:37,515 --> 01:08:38,116 GUT-BRAIN COMMUNICATION IS 1345 01:08:38,116 --> 01:08:40,151 ESTABLISHED BY SENSOR CELLS IN 1346 01:08:40,151 --> 01:08:42,954 THE GUT EPITHELIUM CELLS I'LL BE 1347 01:08:42,954 --> 01:08:45,189 REFERRING TO AS EECs. 1348 01:08:45,189 --> 01:08:48,326 THEY CAN DETECT NUTRIENTS IN THE 1349 01:08:48,326 --> 01:08:51,963 GUT AND CIRCULATE HORMONES AND 1350 01:08:51,963 --> 01:08:54,165 FORM SYNAPSES WITH VAGAL NEURONS 1351 01:08:54,165 --> 01:08:55,934 AND TAKES IT TO THE BRAIN TO 1352 01:08:55,934 --> 01:08:57,402 REGULATE FEEDING BEHAVIOR. 1353 01:08:57,402 --> 01:09:00,738 WHAT I'M INTERESTED IN IS 1354 01:09:00,738 --> 01:09:05,310 UNDERSTANDING HOW THESE SIGNALS 1355 01:09:05,310 --> 01:09:09,113 GO FROM EECs TO THE BRAIN AND 1356 01:09:09,113 --> 01:09:10,815 SPANS ACROSS THE BODY WE NEED A 1357 01:09:10,815 --> 01:09:12,984 MODEL ORGANISM THAT ALLOWS 1358 01:09:12,984 --> 01:09:16,921 ACCESS TO THE WHOLE CIRCUIT. 1359 01:09:16,921 --> 01:09:19,090 FOR THAT WE USED ZEBRAFISH 1360 01:09:19,090 --> 01:09:20,792 BECAUSE THEY'RE SMALL AND 1361 01:09:20,792 --> 01:09:23,895 TRANSPARENT AND MANIPULATE THE 1362 01:09:23,895 --> 01:09:27,065 CELLS OF THE GUT-BRAIN AXIS AND 1363 01:09:27,065 --> 01:09:29,767 THEY'RE A SIMPLE BUT ALSO 1364 01:09:29,767 --> 01:09:33,104 CONSERVED MODEL TO STUDY THIS 1365 01:09:33,104 --> 01:09:33,671 PHENOMENON. 1366 01:09:33,671 --> 01:09:38,543 TO START OFF WE FIRST WANTED TO 1367 01:09:38,543 --> 01:09:42,246 INVESTIGATE WHAT THEY ENCODE. 1368 01:09:42,246 --> 01:09:47,352 WE DEVELOPED AN ANALYSIS 1369 01:09:47,352 --> 01:09:48,920 PIPELINE TO EXTRACT THE 1370 01:09:48,920 --> 01:09:49,921 ACTIVITY. 1371 01:09:49,921 --> 01:09:54,792 WE CAN DETERMINE WHICH NUTRIENTS 1372 01:09:54,792 --> 01:10:00,765 DETERMINE THESE EECs AND WANTED 1373 01:10:00,765 --> 01:10:03,067 TO SEE WHETHER THEY DRIVE 1374 01:10:03,067 --> 01:10:06,871 REPETITIVE PANEL WAYS AND HAVE 1375 01:10:06,871 --> 01:10:08,539 PARTICLES WHICH UPON CONSUMPTION 1376 01:10:08,539 --> 01:10:10,108 DISSOLVE IF THE GUT AND EXPOSE 1377 01:10:10,108 --> 01:10:13,111 THE NUTRIENTS TO THE EECs. 1378 01:10:13,111 --> 01:10:15,113 AND WE CAN LOOK AT HOW MUCH THEY 1379 01:10:15,113 --> 01:10:17,115 EAT FROM THE DIFFERENT PARTICLES 1380 01:10:17,115 --> 01:10:23,621 AND DEVELOP A GUT MEDIATED 1381 01:10:23,621 --> 01:10:24,088 PREFERENCE. 1382 01:10:24,088 --> 01:10:31,896 WE'VE SHOWN THIS AND WHAT I'M 1383 01:10:31,896 --> 01:10:33,898 INTERESTED IS HOW IS THIS 1384 01:10:33,898 --> 01:10:36,434 ENCOENCODE 1385 01:10:36,434 --> 01:10:41,272 ED NERVOUS SYSTEM AND I NEEDED A 1386 01:10:41,272 --> 01:10:44,275 METHOD AND A DEVELOPED A METHOD 1387 01:10:44,275 --> 01:10:48,846 TO GUIDE A NEEDLE INTO THE GUT 1388 01:10:48,846 --> 01:10:51,382 OF ZEBRAFISH AND NOW THAT I'VE 1389 01:10:51,382 --> 01:10:53,785 DEVELOPED THIS METHODOLOGY I CAN 1390 01:10:53,785 --> 01:11:01,626 IMAGE VAGAL NEURONS AND I FOUND 1391 01:11:01,626 --> 01:11:04,162 ENCODING WHERE THE RIGHT VAGAL 1392 01:11:04,162 --> 01:11:06,464 GANGLION HAS MORE DELAYED AND 1393 01:11:06,464 --> 01:11:08,766 THE LEFT HAS MORE IMMEDIATE 1394 01:11:08,766 --> 01:11:12,003 RESPONSES TO THE INJECTED 1395 01:11:12,003 --> 01:11:12,270 STIMULUS. 1396 01:11:12,270 --> 01:11:19,977 I CAN EXPAND THESE PARS OUT THE 1397 01:11:19,977 --> 01:11:21,546 COMPONENTS TO THE INJECTED 1398 01:11:21,546 --> 01:11:21,779 STIMULI. 1399 01:11:21,779 --> 01:11:24,682 I STARTED WITH WHERE THE VAGAL 1400 01:11:24,682 --> 01:11:28,186 BRAIN SYNAPSES ON EXPANDING TO 1401 01:11:28,186 --> 01:11:29,754 OTHER BRAIN REGIONS. 1402 01:11:29,754 --> 01:11:32,590 LASTLY, I WANT TO PHOTO 1403 01:11:32,590 --> 01:11:37,728 STIMULATE THESE AND RECORD THE 1404 01:11:37,728 --> 01:11:43,968 NEURAL RESPONSES AND I ADAPT THE 1405 01:11:43,968 --> 01:11:46,270 NEEDLE TO GUIDE THE OPTIC FIBER 1406 01:11:46,270 --> 01:11:49,507 TO THE SIDE OF THE FISH AND 1407 01:11:49,507 --> 01:11:50,108 PHOTO STIMULATE THESE THROUGH 1408 01:11:50,108 --> 01:11:56,380 IMAGING. 1409 01:11:56,380 --> 01:12:00,017 AND FOR THAT WE DEVELOPED THE 1410 01:12:00,017 --> 01:12:02,220 EECs AND I'M WORKING ON 1411 01:12:02,220 --> 01:12:04,755 OPTIMIZING THESE EXPERIMENTS. 1412 01:12:04,755 --> 01:12:07,191 OVER ALL MY THESIS WORK AIMS TO 1413 01:12:07,191 --> 01:12:09,060 DEVELOP A COMPREHENSIVE 1414 01:12:09,060 --> 01:12:12,430 INFORMATION OF THE GUT-BRAIN 1415 01:12:12,430 --> 01:12:13,865 NEURAL CIRCUITRY AND WHAT THE 1416 01:12:13,865 --> 01:12:17,401 GUT IS COMMUNICATING TO THE 1417 01:12:17,401 --> 01:12:18,669 BRAIN. 1418 01:12:18,669 --> 01:12:19,270 WE WERE ASKED TO PRESENT 1419 01:12:19,270 --> 01:12:20,438 SOMETHING SPECIAL ABOUT 1420 01:12:20,438 --> 01:12:22,507 OURSELVES. 1421 01:12:22,507 --> 01:12:29,947 I'M A FIRST GEN GRAD STUDENT 1422 01:12:29,947 --> 01:12:32,083 BORN AND RAISED IN TURKEY AND 1423 01:12:32,083 --> 01:12:35,620 I'D LOVE TO GIVEBACK AND MENTOR 1424 01:12:35,620 --> 01:12:36,387 HIGH SCHOOL STUDENTS AND 1425 01:12:36,387 --> 01:12:38,456 UNDERGRAD STUDENTS. 1426 01:12:38,456 --> 01:12:43,628 I'D LIKE TO HIGHLIGHT WHO 1427 01:12:43,628 --> 01:12:53,704 AMAZING UNDER GRADS WITH ME AND 1428 01:12:53,704 --> 01:12:55,273 THERE'S WORK ON A PROJECT WHERE 1429 01:12:55,273 --> 01:12:57,808 WE INVESTIGATE THE EFFECTS OF 1430 01:12:57,808 --> 01:13:00,444 PSYCHEDELICS ON THE 1431 01:13:00,444 --> 01:13:04,315 TRANSFORMATION IN FISH. 1432 01:13:04,315 --> 01:13:09,887 I DON'T HAVE MUCH TIME BUT THE 1433 01:13:09,887 --> 01:13:10,321 MOS 1434 01:13:10,321 --> 01:13:12,456 POSTER MEETING IS 64 AND WILL 1435 01:13:12,456 --> 01:13:14,992 PRESENT TOMORROW AND MY POSTER 1436 01:13:14,992 --> 01:13:17,528 NUMBER FOR THAT IS 2 AND REACH 1437 01:13:17,528 --> 01:13:20,131 OUT BY E-MAIL OR FIND ME ON 1438 01:13:20,131 --> 01:13:20,464 LINKEDIN OR X. 1439 01:13:20,464 --> 01:13:28,773 THANK YOU. 1440 01:13:28,773 --> 01:13:29,774 >> THANK YOU. 1441 01:13:29,774 --> 01:13:35,479 KHALIL RAMADI, PLEASE. 1442 01:13:35,479 --> 01:13:41,185 >> GOOD MORNING, EVERYONE I'M AN 1443 01:13:41,185 --> 01:13:46,023 ASSISTANT PROFESSOR AT NYU AND 1444 01:13:46,023 --> 01:13:49,594 TODAY IN THE QUICKEST TALK ON 1445 01:13:49,594 --> 01:13:56,100 THIS TOPIC I'LL TALK ABOUT 1446 01:13:56,100 --> 01:14:00,805 INGESTIBLE MODULATION DEVICE AND 1447 01:14:00,805 --> 01:14:03,975 LOOKING AT STIMULATION RESEARCH 1448 01:14:03,975 --> 01:14:07,778 IN THE '60s AFTER PACE MAKERS 1449 01:14:07,778 --> 01:14:10,181 REVOLUTIONIZED CARDIOLOGY AND WE 1450 01:14:10,181 --> 01:14:11,182 THOUGHT WE SHOULD BE ABLE TO 1451 01:14:11,182 --> 01:14:12,583 MAKE THE STOMACH BEAT. 1452 01:14:12,583 --> 01:14:18,256 THAT LED TO WHAT WE HAVE THAT IS 1453 01:14:18,256 --> 01:14:19,290 CLINICALLY APPROVED GES SYSTEMS 1454 01:14:19,290 --> 01:14:26,497 WHICH ARE PACE MAKERS SURGICALLY 1455 01:14:26,497 --> 01:14:29,500 IMPLANTED WITH SUTURE TO THE 1456 01:14:29,500 --> 01:14:36,340 STOMACH AND HELPS PATIENTS WITH 1457 01:14:36,340 --> 01:14:41,312 NAUSEA, VOMITING SYMPTOMS FROM 1458 01:14:41,312 --> 01:14:41,646 GASTROPARESIS. 1459 01:14:41,646 --> 01:14:44,782 IT DOESN'T MAKE THE STOMACH BEAT 1460 01:14:44,782 --> 01:14:50,454 BUT THE REASON WHY IT IS FDA 1461 01:14:50,454 --> 01:14:52,857 APPROVED IT IS PATIENTS REPORT 1462 01:14:52,857 --> 01:14:54,558 BETTER OUTCOME AND WE THOUGHT 1463 01:14:54,558 --> 01:14:59,263 MAYBE IT'S A CENTRALLY MEDIATED 1464 01:14:59,263 --> 01:15:02,133 SYSTEM RESOLVED THROUGH THIS 1465 01:15:02,133 --> 01:15:02,533 STIMULATION. 1466 01:15:02,533 --> 01:15:08,939 THE HYPOTHESIS IS PERHAPS IT'S 1467 01:15:08,939 --> 01:15:12,910 IMPROVING NAUSEA AND VOMITING 1468 01:15:12,910 --> 01:15:18,883 INCREASING GHRELIN LEVELS AND TO 1469 01:15:18,883 --> 01:15:21,419 TEST THIS WE USED SWINE MODELS 1470 01:15:21,419 --> 01:15:26,824 AND WENT IN WITH ELECTRODES AND 1471 01:15:26,824 --> 01:15:28,059 SAMPLED BLOOD AFTER STIMULATION 1472 01:15:28,059 --> 01:15:29,327 UP TO 60 MINUTES AND WE SAW IF 1473 01:15:29,327 --> 01:15:31,829 YOU YOU LOOK AT THE CHANGE IN 1474 01:15:31,829 --> 01:15:35,066 GHRELIN LEVELS OVER TIME THE 1475 01:15:35,066 --> 01:15:37,768 CASES WHERE ANIMALS RECEIVE 1476 01:15:37,768 --> 01:15:39,203 ACTIVE STIMULATION SAW 1477 01:15:39,203 --> 01:15:40,104 SIGNIFICANT INCREASE IN GHRELIN 1478 01:15:40,104 --> 01:15:44,041 NOT THERE IN THE SHAM AND IF YOU 1479 01:15:44,041 --> 01:15:48,045 DO VAGOTOMY IT SEEMS TO BE 1480 01:15:48,045 --> 01:15:49,980 HORMONAL AFFECT MEDIATED SOME 1481 01:15:49,980 --> 01:15:50,448 NEURAL REFLEX. 1482 01:15:50,448 --> 01:15:52,316 THE SECOND QUESTION IS WHETHER 1483 01:15:52,316 --> 01:15:55,019 WE COULD ACCOMPLISH SIMILAR TYPE 1484 01:15:55,019 --> 01:15:57,955 OF STIMULATION THROUGH 1485 01:15:57,955 --> 01:16:00,124 INGESTIBLE SYSTEMS AND LED TO US 1486 01:16:00,124 --> 01:16:05,096 DEVELOP FLUID WE CAN CAPSULE FOR 1487 01:16:05,096 --> 01:16:08,666 HORMONE MODULATION AND DEVELOP A 1488 01:16:08,666 --> 01:16:16,774 TECHNOLOGY AND FLASH IS ROUGHLY 1489 01:16:16,774 --> 01:16:19,043 THE SIZE OF THE LARGEST HUMAN 1490 01:16:19,043 --> 01:16:21,412 CAP TOOL SIZE AND HAVE 1491 01:16:21,412 --> 01:16:28,185 ELECTRONICS AND PUT OUT OUT THE 1492 01:16:28,185 --> 01:16:32,423 SUFFER FAS AND EXISTS IN AN OPEN 1493 01:16:32,423 --> 01:16:36,227 SURFACE STATE AND WHEN THEY COME 1494 01:16:36,227 --> 01:16:40,097 INTO CONTACT STIMULATION STARTS 1495 01:16:40,097 --> 01:16:40,631 TO FLOW. 1496 01:16:40,631 --> 01:16:42,366 THERE'S A LOT OF ENGINEERING AND 1497 01:16:42,366 --> 01:16:47,037 ONE FEATURE WHICH WAS COUNTER 1498 01:16:47,037 --> 01:16:53,711 INTUITIVE AND YOU CAN SEE THE 1499 01:16:53,711 --> 01:16:55,846 SURFACE AND HAVE YOU GROUPS AND 1500 01:16:55,846 --> 01:17:00,484 WE RECOGNIZED THE PRESENCE OF 1501 01:17:00,484 --> 01:17:05,423 GASTRIC FLUID STIMULI CAN NO 1502 01:17:05,423 --> 01:17:11,061 LONGER ENTER THE TISSUES AND WE 1503 01:17:11,061 --> 01:17:12,396 HAVE A MEANS OF WICKING FLUID 1504 01:17:12,396 --> 01:17:14,365 AWAY FROM THE POINT OF CONTACT 1505 01:17:14,365 --> 01:17:18,903 BETWEEN THE ELECTRODE AND 1506 01:17:18,903 --> 01:17:19,170 TISSUE. 1507 01:17:19,170 --> 01:17:24,442 THIS IS A CAPSULE AND YOU CAN 1508 01:17:24,442 --> 01:17:27,978 SEE THE FLUID IS WICKED FROM THE 1509 01:17:27,978 --> 01:17:28,879 SURFACE ALLOWING FOR BETTER 1510 01:17:28,879 --> 01:17:31,682 CONTACT BETWEEN ELECTRODE AND 1511 01:17:31,682 --> 01:17:31,982 TISSUE. 1512 01:17:31,982 --> 01:17:33,984 IF YOU LOOKING AT THE SAME 1513 01:17:33,984 --> 01:17:36,120 EFFECT OF LOOKING AT GHRELIN 1514 01:17:36,120 --> 01:17:39,924 LEVELS OVER TIME IF YOU YOU 1515 01:17:39,924 --> 01:17:46,330 DELIVER ACTIVE CAPSULE OPPOSED 1516 01:17:46,330 --> 01:17:48,432 TO OTHERS YOU SEE ACTIVATED 1517 01:17:48,432 --> 01:17:51,869 GHRELIN LEVELS. 1518 01:17:51,869 --> 01:17:54,572 I WANT TO ACKNOWLEDGE PEOPLE IN 1519 01:17:54,572 --> 01:18:00,444 MY GROUP AND NYU AND FORMER 1520 01:18:00,444 --> 01:18:02,880 COLLABORATORS AT M.I.T. AND 1521 01:18:02,880 --> 01:18:05,683 FUNDING SOURCES. 1522 01:18:05,683 --> 01:18:09,520 I'M EXCITED ABOUT THIS INGEST 1523 01:18:09,520 --> 01:18:12,223 IBLE ELECTRONIC SPACE AND CAN DO 1524 01:18:12,223 --> 01:18:15,659 NEUROMODULATION IN A SOMEWHAT 1525 01:18:15,659 --> 01:18:18,362 TARGETED WAY AND WOULD LOVE 1526 01:18:18,362 --> 01:18:22,333 THOUGHTS AND COMMENTS AND WE'RE 1527 01:18:22,333 --> 01:18:23,367 RECRUITING ACROSS THE BOARD AND 1528 01:18:23,367 --> 01:18:25,736 MY POSTER NUMBER IS 68. 1529 01:18:25,736 --> 01:18:26,337 WOULD LOVE TO CHAT LATER. 1530 01:18:26,337 --> 01:18:36,514 THANK YOU. 1531 01:18:44,855 --> 01:18:49,493 >> 1532 01:18:49,493 --> 01:18:51,962 >> THANK YOU TO EVERYBODY 1533 01:18:51,962 --> 01:18:54,899 ESPECIALLY TO THE ORGANIZERS. 1534 01:18:54,899 --> 01:18:56,901 I'M GOING TO TELL BUT A NEW SET 1535 01:18:56,901 --> 01:19:00,437 OF DATA FROM OUR LAB WE'RE 1536 01:19:00,437 --> 01:19:01,138 EXCITE ABOUT. 1537 01:19:01,138 --> 01:19:06,577 WE START FROM THIS QUESTION, DO 1538 01:19:06,577 --> 01:19:07,244 INTEROCEPTIVE SIGNALS INFLUENCE 1539 01:19:07,244 --> 01:19:07,711 DECISION MAKE. 1540 01:19:07,711 --> 01:19:09,446 BEFORE I TELL YOU HOW WE ASK 1541 01:19:09,446 --> 01:19:11,282 THIS IN MONKEYS I WANT TO ASK 1542 01:19:11,282 --> 01:19:13,551 THE AUDIENCE TO JOIN MYSELF AND 1543 01:19:13,551 --> 01:19:16,387 THE REST OF TUCSON IN 1544 01:19:16,387 --> 01:19:17,087 UNDERSTANDING OR NOT 1545 01:19:17,087 --> 01:19:18,822 UNDERSTANDING BUT MAKING A 1546 01:19:18,822 --> 01:19:20,758 DECISION IF LIVING IN THE CITY 1547 01:19:20,758 --> 01:19:22,092 WITH THE BEST 23 MILES OF 1548 01:19:22,092 --> 01:19:24,762 MEXICAN FOOD IN THE COUNTRY IS 1549 01:19:24,762 --> 01:19:31,135 WORTH THE 110 DEGREE SUMMERS. 1550 01:19:31,135 --> 01:19:33,604 THIS SETS UP A CONFLICT AFTER 1551 01:19:33,604 --> 01:19:35,306 WEIGH THE COST AND BENEFITS OF 1552 01:19:35,306 --> 01:19:36,540 THAT OPTION. 1553 01:19:36,540 --> 01:19:39,443 IF WE WANT TO KNOW HOW 1554 01:19:39,443 --> 01:19:40,811 INTEROCEPTION INFLUENCES THESE 1555 01:19:40,811 --> 01:19:44,248 DECISIONS WE'RE GOING TO USE A 1556 01:19:44,248 --> 01:19:45,950 PERIPHERAL SPECIFIC 1557 01:19:45,950 --> 01:19:46,283 MANIPULATION. 1558 01:19:46,283 --> 01:19:49,420 WE USED A NON-SPECIFIC 1559 01:19:49,420 --> 01:19:53,791 ANTAGONIST THAT DOES NOT CROSS 1560 01:19:53,791 --> 01:19:55,793 THE BLOOD BRAIN BARRIER AND 1561 01:19:55,793 --> 01:20:06,337 EFFECTS OF THIS DRUG CAN BE USED 1562 01:20:08,772 --> 01:20:13,243 AND IT BLOCKS THE 1563 01:20:13,243 --> 01:20:13,911 PARASYMPATHETIC SYSTEM AND WHAT 1564 01:20:13,911 --> 01:20:16,246 DO WE DO WITH THE MONKEYS? 1565 01:20:16,246 --> 01:20:19,083 THEY'RE SEATED IN THE CHAIR WITH 1566 01:20:19,083 --> 01:20:20,985 A DEVICE WITH TEMPERATURE 1567 01:20:20,985 --> 01:20:22,953 RESTRICTED CONTROL AS WELL AS A 1568 01:20:22,953 --> 01:20:24,088 JUICE TUBE AND TOUCH SWITCH. 1569 01:20:24,088 --> 01:20:27,224 AT THE BEGINNING OF EVERY TRIAL 1570 01:20:27,224 --> 01:20:30,194 THE THERMO RAMPS UP TO A PRE 1571 01:20:30,194 --> 01:20:31,061 DETERMINED TEMPERATURE AND THE 1572 01:20:31,061 --> 01:20:34,465 JUICE IS DELIVERED AT A RATE OF 1573 01:20:34,465 --> 01:20:36,333 ONE DROP PER SECOND AND WHEN THE 1574 01:20:36,333 --> 01:20:38,268 MONKEY NO LONGER WANTS TO DEAL 1575 01:20:38,268 --> 01:20:40,070 WITH THE HEAT THEY CAN TURN OFF 1576 01:20:40,070 --> 01:20:42,573 THE JUICE AND HEAT. 1577 01:20:42,573 --> 01:20:44,808 THIS GIVES US A MEASURE OF THEIR 1578 01:20:44,808 --> 01:20:46,810 TOLERANCE FOR THE HEAT GIVEN THE 1579 01:20:46,810 --> 01:20:48,245 JUICE REWARD. 1580 01:20:48,245 --> 01:20:51,482 EVERY DAY WE GIVE THEM THIS FOR 1581 01:20:51,482 --> 01:20:52,983 25 MINUTES AND DO A ROUND OF NO 1582 01:20:52,983 --> 01:20:54,652 HEAT TRIALS WHERE THE HEAT 1583 01:20:54,652 --> 01:20:58,088 DOESN'T RAMP UP IT JUST STAYS 1584 01:20:58,088 --> 01:20:59,623 CONSTANT AND THEY DRINK THE USE 1585 01:20:59,623 --> 01:21:01,492 AND THEN AROUND THE HEAT TRIALS. 1586 01:21:01,492 --> 01:21:03,727 THAT CAN BE SWAPPED FROM DAY TO 1587 01:21:03,727 --> 01:21:14,271 DAY TO ACCOUNT FOR SATIATION AND 1588 01:21:22,012 --> 01:21:24,214 WHEN WE GIVE THIS IT SHIFTS BACK 1589 01:21:24,214 --> 01:21:26,650 INDICATING THE ANIMAL IS MORE 1590 01:21:26,650 --> 01:21:28,252 AVOIDANT TO THE HEAT AND IN 1591 01:21:28,252 --> 01:21:28,919 GENERAL LESS WILLING TO TOLERATE 1592 01:21:28,919 --> 01:21:38,996 IT. 1593 01:21:50,007 --> 01:21:53,577 WHEN LOOK AT THE NO HEAT TRIALS 1594 01:21:53,577 --> 01:21:55,112 THERE'S NO TIME THEY STOP THE 1595 01:21:55,112 --> 01:21:58,782 JUICE SAYING IT'S NOT ABOUT THE 1596 01:21:58,782 --> 01:22:01,385 REWARD BUT AN AVOIDANT BEHAVIOR 1597 01:22:01,385 --> 01:22:03,787 AND I CAN'T SHOW YOU EVERY 1598 01:22:03,787 --> 01:22:06,824 CONTROL BUT WE DID A LOT AND YOU 1599 01:22:06,824 --> 01:22:10,327 CAN COME TO THE POSTER AND WE 1600 01:22:10,327 --> 01:22:20,871 USE THE BETA AGONIST AND AND IT 1601 01:22:22,072 --> 01:22:31,915 COMES OUT SIMILAR. 1602 01:22:31,915 --> 01:22:35,719 AND PRIMATES SHINE ALONG THE 1603 01:22:35,719 --> 01:22:38,055 INTEROCEPTIVE PATHWAYS AND WE 1604 01:22:38,055 --> 01:22:40,057 HAVE AN AWESOME MASTER STUDENT 1605 01:22:40,057 --> 01:22:42,860 WHO IS APPLYING TO Ph.D. PROGRAM 1606 01:22:42,860 --> 01:22:48,665 SO YOU'D LIKE HER E-MAIL AN WANT 1607 01:22:48,665 --> 01:22:50,100 A GREAT Ph.D. STUDENT, PLEASE 1608 01:22:50,100 --> 01:22:51,969 LET ME KNOW. 1609 01:22:51,969 --> 01:22:56,240 THANK YOU. 1610 01:22:56,240 --> 01:22:58,909 >> THANK YOU. 1611 01:22:58,909 --> 01:23:09,419 WE'RE PLEASED TO HAVE SENEGAL. 1612 01:23:09,953 --> 01:23:10,721 >> GOOD MORNING. 1613 01:23:10,721 --> 01:23:12,356 I'M A THIRD-YEAR DOCTORAL 1614 01:23:12,356 --> 01:23:14,725 STUDENT IN THE DEPARTMENT OF 1615 01:23:14,725 --> 01:23:16,426 PSYCHOLOGY IN THE COLLEGE OF 1616 01:23:16,426 --> 01:23:18,128 HUMAN ECOLOGY AT CORNELL 1617 01:23:18,128 --> 01:23:18,462 INVESTIGATION. 1618 01:23:18,462 --> 01:23:22,499 MY ADVISERS IS ADAM ANDERSON AND 1619 01:23:22,499 --> 01:23:24,568 LEADERS IN THE FIELD OF EMOTION 1620 01:23:24,568 --> 01:23:27,237 AND NEUROCHEMISTRY. 1621 01:23:27,237 --> 01:23:30,774 MY WORK EXAMINES THE HEART-BRAIN 1622 01:23:30,774 --> 01:23:32,709 AXIS IN PARKINSON'S DISEASE AND 1623 01:23:32,709 --> 01:23:42,986 THIS IS MY TEAM. 1624 01:23:50,761 --> 01:23:56,233 THAT'S US ATTENDING MOVING DAY 1625 01:23:56,233 --> 01:23:59,970 IN RODCHESTER SUPPORTING 1626 01:23:59,970 --> 01:24:02,506 FAMILIES WITH PARKINSON'S DAY. 1627 01:24:02,506 --> 01:24:04,675 IT'S ONLY WORKING WITH TEAMS 1628 01:24:04,675 --> 01:24:08,645 WHERE WE'VE BEEN ABLE TO LOOK AT 1629 01:24:08,645 --> 01:24:11,181 WHERE THE DISEASE FIRST STARTS 1630 01:24:11,181 --> 01:24:13,283 AND THE AUTONOMIC SYSTEM CHANGES 1631 01:24:13,283 --> 01:24:16,887 AND THE HISTORY OF HEART ATTACK, 1632 01:24:16,887 --> 01:24:20,424 AND HISTORY OF SMOKING REDUCES 1633 01:24:20,424 --> 01:24:20,991 THE DIAGNOSIS. 1634 01:24:20,991 --> 01:24:25,863 THERE'S JUST THE BEGINNING OF 1635 01:24:25,863 --> 01:24:27,297 UNDERSTANDING WHAT'S HAPPENING 1636 01:24:27,297 --> 01:24:28,966 IN THIS CONDITION. 1637 01:24:28,966 --> 01:24:33,070 HERE'S AN EXAMPLE OF BEING 1638 01:24:33,070 --> 01:24:34,171 EMBEDDED IN THESE COMMUNITIES 1639 01:24:34,171 --> 01:24:35,672 SUPPORTS QUESTIONS AND WE'VE 1640 01:24:35,672 --> 01:24:40,510 BEEN WORKING TO UNDERSTAND HOW 1641 01:24:40,510 --> 01:24:42,212 THIS INTERESTING CARDIO 1642 01:24:42,212 --> 01:24:50,754 PULMONARY WORKOUT REDUCES MOTOR 1643 01:24:50,754 --> 01:24:53,257 GAIT SYSTEMS AND HE SAID WHEN 1644 01:24:53,257 --> 01:24:54,725 THEY COME OFF THE MACHINE IT'S 1645 01:24:54,725 --> 01:24:55,692 LIKE THEY DON'T FEEL ANYTHING 1646 01:24:55,692 --> 01:24:57,995 AND WE ASKED HOW STRONGLY CAN 1647 01:24:57,995 --> 01:24:59,563 THEY FEEL THEIR HEART RATE 1648 01:24:59,563 --> 01:25:01,932 DURING THREE EXERCISE TRAINING 1649 01:25:01,932 --> 01:25:02,199 SESSIONS. 1650 01:25:02,199 --> 01:25:04,101 EACH 45 SECONDS EACH AND FOUND 1651 01:25:04,101 --> 01:25:06,970 THE TRAINING SESSIONS LED TO A 1652 01:25:06,970 --> 01:25:09,606 20 BEATS PER MINUTE HEART RATE 1653 01:25:09,606 --> 01:25:09,873 INCREASE. 1654 01:25:09,873 --> 01:25:13,443 FIRST, THE HOST LIKELY RESPONSE 1655 01:25:13,443 --> 01:25:14,745 ACROSS THE BASELINE THE REACT 1 1656 01:25:14,745 --> 01:25:16,213 AND REACT 3 AND RECOVERY PERIOD 1657 01:25:16,213 --> 01:25:17,147 WERE NOT AT ALL. 1658 01:25:17,147 --> 01:25:19,583 NOT AT ALL BEING ABLE TO FEEL 1659 01:25:19,583 --> 01:25:20,017 THEIR HEARTBEAT. 1660 01:25:20,017 --> 01:25:21,952 I'M PLAYING MY SLIDES QUICKLY 1661 01:25:21,952 --> 01:25:25,622 FOR YOU RIGHT NOW OF THEIR 1662 01:25:25,622 --> 01:25:27,557 ACTUAL RESPONSES PLOTTED AGAINST 1663 01:25:27,557 --> 01:25:29,259 HEART RATE AND FOR THE MOST PART 1664 01:25:29,259 --> 01:25:33,530 THERE'S NOT A STRONG POSITIVE 1665 01:25:33,530 --> 01:25:34,197 RELATIONSHIP BETWEEN HEART RATE 1666 01:25:34,197 --> 01:25:34,932 AND RESPONSE. 1667 01:25:34,932 --> 01:25:37,100 WE'RE SEEING A STRONG NEGATIVE 1668 01:25:37,100 --> 01:25:38,969 RELATIONSHIP FOR ONE OF OUR 1669 01:25:38,969 --> 01:25:39,670 PARTICIPANTS WHERE INCREASE IN 1670 01:25:39,670 --> 01:25:41,538 HEART RATE IS MOVING THEM TO 1671 01:25:41,538 --> 01:25:43,740 REPORT NOT AT ALL FOR THEIR 1672 01:25:43,740 --> 01:25:45,876 HEART RATE RESPONSE AND LOOKING 1673 01:25:45,876 --> 01:25:47,210 AT EACH INDIVIDUAL PARTICIPANT 1674 01:25:47,210 --> 01:25:49,880 WE'RE SEEING ONLY TWO IS THERE 1675 01:25:49,880 --> 01:25:51,014 DIFFERENCES BETWEEN THE MEDIANS 1676 01:25:51,014 --> 01:25:52,883 OF RESPONSES ON THIS QUESTION OF 1677 01:25:52,883 --> 01:25:53,850 HOW STRONGLY CAN THEY FEEL THEIR 1678 01:25:53,850 --> 01:25:56,853 HEART RATE. 1679 01:25:56,853 --> 01:25:59,756 NEXT WE ALSO WANTED TO COLLECT 1680 01:25:59,756 --> 01:26:01,124 SOME DATA ON STRESS. 1681 01:26:01,124 --> 01:26:03,260 NOT JUST EXERCISE BUT TAKING 1682 01:26:03,260 --> 01:26:07,998 THEM IN THE CORNELL MAGNETIC 1683 01:26:07,998 --> 01:26:09,967 IMAGING FACILITY AND RECORDING 1684 01:26:09,967 --> 01:26:11,168 THEIR RESPONSES WHERE THEY'RE 1685 01:26:11,168 --> 01:26:12,936 PAYING ATTENTION TO THE SCREEN 1686 01:26:12,936 --> 01:26:16,506 AS A BASELINE LOOKING AT A 1687 01:26:16,506 --> 01:26:19,042 RESTING STATE AND FIXATION AND 1688 01:26:19,042 --> 01:26:20,777 THEN TELLING THEM YOU HAVE TWO 1689 01:26:20,777 --> 01:26:28,185 MINUTES TO PREPARE A SPEECH 1690 01:26:28,185 --> 01:26:29,853 ABOUT WHY YOU'RE A GOOD FRIEND 1691 01:26:29,853 --> 01:26:33,323 AN TELLING THEM THE COIN FLIP IS 1692 01:26:33,323 --> 01:26:36,927 THE DECIDING TO NOT MAKE THE 1693 01:26:36,927 --> 01:26:39,229 SPEECH AND THAT'S OUR BASELINE 1694 01:26:39,229 --> 01:26:43,066 AND STRESS AND RECOVERY AND WITH 1695 01:26:43,066 --> 01:26:46,670 STRESS WE'RE SEEING 20 MINUTES A 1696 01:26:46,670 --> 01:26:51,775 MINUTE HEART RATE INCREASE AND 1697 01:26:51,775 --> 01:26:54,911 SEEING AN INDICATION THERE'S 1698 01:26:54,911 --> 01:26:56,880 MORE PHYSIOLOGIC CONSEQUENCES OF 1699 01:26:56,880 --> 01:26:58,448 STRESS IN PARKINSON'S AND WE 1700 01:26:58,448 --> 01:27:01,385 HAVE THEM -- THEY'RE RESPONSES 1701 01:27:01,385 --> 01:27:02,886 ARE ROUGHLY THE SAME ON STRESS 1702 01:27:02,886 --> 01:27:06,123 MAYBE PEOPLE WITH PARKINSON'S 1703 01:27:06,123 --> 01:27:09,092 RECOVER LATE SLOWER BUT OUR 1704 01:27:09,092 --> 01:27:10,160 INTEROCEPTION QUESTION HOW 1705 01:27:10,160 --> 01:27:11,661 STRONGLY THEY CAN FEEL THEIR 1706 01:27:11,661 --> 01:27:15,932 HEARTBEAT THEY SAY NOT AT ALL SO 1707 01:27:15,932 --> 01:27:18,035 WE'RE STILL SEEING THEM STRUGGLE 1708 01:27:18,035 --> 01:27:21,038 TO TAP INTO THEIR INTEROCEPTIVE 1709 01:27:21,038 --> 01:27:21,705 ABILITY. 1710 01:27:21,705 --> 01:27:24,307 I MENTIONED THIS IS HAPPENING 1711 01:27:24,307 --> 01:27:30,280 WITH A RESTING STATE FUNCTIONAL 1712 01:27:30,280 --> 01:27:32,716 MRI SCAN AND IT'S STRONG 1713 01:27:32,716 --> 01:27:34,885 CONNECTIVITY WITH ITSELF AND 1714 01:27:34,885 --> 01:27:36,420 LOOKING SIMILAR ACROSS THE 1715 01:27:36,420 --> 01:27:38,955 PARKINSON'S AND HEALTHY CONTROL 1716 01:27:38,955 --> 01:27:40,957 AND IN STRESS WE'RE SEEING 1717 01:27:40,957 --> 01:27:43,560 INCREASES IN FUNCTIONAL 1718 01:27:43,560 --> 01:27:44,961 CONNECTIVITY FOR OUR HEALTHY 1719 01:27:44,961 --> 01:27:46,229 PARTICIPANT IT'S POSITIVE 1720 01:27:46,229 --> 01:27:50,600 INCREASES PARTICULARLY IN THE 1721 01:27:50,600 --> 01:27:53,170 CEREBELLUM AND FOR FOLKS WITH 1722 01:27:53,170 --> 01:27:54,771 PARKINSON'S NEGATIVE IN THE 1723 01:27:54,771 --> 01:27:57,741 CEREBELLUM A CRITICAL REGION FOR 1724 01:27:57,741 --> 01:27:59,276 CARDIAC REPRESENTATION AND PLAYS 1725 01:27:59,276 --> 01:28:02,412 A ROLE IN THE AUTONOMIC NERVOUS 1726 01:28:02,412 --> 01:28:04,314 SYSTEM AND PARKINSON'S SYMPTOMS. 1727 01:28:04,314 --> 01:28:07,484 WE'LL CONTINUE TO LOOK AT THE 1728 01:28:07,484 --> 01:28:09,953 INTER 1729 01:28:09,953 --> 01:28:12,956 INTER 1730 01:28:12,956 --> 01:28:17,661 INTERIOR INSULA CEREBELLUM AND 1731 01:28:17,661 --> 01:28:24,734 THANK YOU TO MY CORNELL TEAM AND 1732 01:28:24,734 --> 01:28:29,005 THE MARINE BIOLOGICAL SPINES 1733 01:28:29,005 --> 01:28:30,040 PROGRAM AND UNIVERSITY OF 1734 01:28:30,040 --> 01:28:32,609 WISCONSIN AND FIND ME AT THE 1735 01:28:32,609 --> 01:28:33,977 SOCIETY FOR NEUROSCIENCE POSTER 1736 01:28:33,977 --> 01:28:34,177 HALL. 1737 01:28:34,177 --> 01:28:42,686 THANK YOU VERY MUCH. 1738 01:28:42,686 --> 01:28:45,755 >> THANK YOU. 1739 01:28:45,755 --> 01:28:50,527 DR. ZHANG, PLEASE. 1740 01:28:50,527 --> 01:28:54,197 >> THANK YOU FOR THE 1741 01:28:54,197 --> 01:28:55,465 OPPORTUNITY. 1742 01:28:55,465 --> 01:28:59,736 I'M AN ASSISTANT PROFESSOR OF 1743 01:28:59,736 --> 01:29:00,403 NEUROLOGY AND NEUROSCIENCE AT 1744 01:29:00,403 --> 01:29:03,039 YALE UNIVERSITY FOR THREE YEARS 1745 01:29:03,039 --> 01:29:07,511 AND UNDERSTANDING PARKINSON'S 1746 01:29:07,511 --> 01:29:08,445 DISEASE WITH INTERACTIONS AND 1747 01:29:08,445 --> 01:29:11,548 BRAIN COMMUNICATION. 1748 01:29:11,548 --> 01:29:13,984 PARKINSON'S DISEASE IS THE 1749 01:29:13,984 --> 01:29:20,190 SECOND MOST COMMON NEURO 1750 01:29:20,190 --> 01:29:22,325 DEGENERATIVE DISEASE. 1751 01:29:22,325 --> 01:29:24,427 THE PATIENT HAS SYMPTOMS 1752 01:29:24,427 --> 01:29:31,735 INCLUDING G.I. SYMPTOMS. 1753 01:29:31,735 --> 01:29:36,339 THE PATHOLOGY LOOKING AT 1754 01:29:36,339 --> 01:29:41,278 INITIATION IN THE GUT AND THE 1755 01:29:41,278 --> 01:29:44,381 VAGAL NERVE TO THE BRAIN. 1756 01:29:44,381 --> 01:29:47,217 OUR T CELLS HAVE BEEN IDENTIFIED 1757 01:29:47,217 --> 01:29:51,955 IN THE PARKINSON'S PATIENT 1758 01:29:51,955 --> 01:29:56,459 SUGGESTING IN ADDITION TO THE 1759 01:29:56,459 --> 01:30:03,567 ACCESS MEDIATED BY THE NERVES. 1760 01:30:03,567 --> 01:30:06,570 IMMUNE CELLS BRING CONNECTION TO 1761 01:30:06,570 --> 01:30:07,304 PARKINSON'S DISEASE. 1762 01:30:07,304 --> 01:30:10,440 OUR CENTRAL HYPOTHESIS AT THE 1763 01:30:10,440 --> 01:30:16,980 SUBSET OF PATIENTS, PARKINSON'S 1764 01:30:16,980 --> 01:30:21,251 INCLUDING NUCLEI IN THE GUT AND 1765 01:30:21,251 --> 01:30:27,057 IT'S A DISEASE IN THE BRAIN. 1766 01:30:27,057 --> 01:30:30,794 OUR STUDIES FOCUSSING ON HUMAN 1767 01:30:30,794 --> 01:30:35,332 RESEARCH WE RELY ON HUMAN 1768 01:30:35,332 --> 01:30:37,701 CONTROLS FROM EARLY PARKINSON'S 1769 01:30:37,701 --> 01:30:39,302 DISEASE WHO HAVE REM SLEEP 1770 01:30:39,302 --> 01:30:41,705 BEHAVIOR AND ACT OUT THEIR DREAM 1771 01:30:41,705 --> 01:30:42,539 DURING SLEEP. 1772 01:30:42,539 --> 01:30:49,279 FROM THE SAME PATIENT DONORS 1773 01:30:49,279 --> 01:30:53,817 BLOOD AND GUT BIOPSY WE ISOLATED 1774 01:30:53,817 --> 01:31:00,423 THE CELLS ACROSS ORGANS AND 1775 01:31:00,423 --> 01:31:06,029 PERFORMED SINGLE CELL RNA 1776 01:31:06,029 --> 01:31:07,998 SEQUENCING AND T CELL SEQUENCING 1777 01:31:07,998 --> 01:31:10,834 CAN SERVE AS A POSSIBLE CURE FOR 1778 01:31:10,834 --> 01:31:14,838 THE T CELL ACROSS ORGANS. 1779 01:31:14,838 --> 01:31:24,881 CSF IS A WINDOW TO SEE WHAT'S 1780 01:31:24,881 --> 01:31:29,419 HAPPENING IN THE BRAIN AND. 1781 01:31:29,419 --> 01:31:34,758 AND THIS IS THE INTEGRATION OF 1782 01:31:34,758 --> 01:31:37,727 THE T CELLS FROM ORGANS 1783 01:31:37,727 --> 01:31:40,430 INCLUDING THE CSF TO THE 1784 01:31:40,430 --> 01:31:43,300 COLLECTION OF T CELLS AND THE 1785 01:31:43,300 --> 01:31:43,533 COLON. 1786 01:31:43,533 --> 01:31:46,703 THE T CELLS FROM THE ORGANS HAVE 1787 01:31:46,703 --> 01:31:52,442 A UNIQUE SIGNATURE FOR IMPULSE 1788 01:31:52,442 --> 01:31:57,981 ENRICHED IN THE CSF AND THE 1789 01:31:57,981 --> 01:32:00,583 CHEMICAL RECEPTOR AND IT IS 1790 01:32:00,583 --> 01:32:03,186 PLAYING AN ESSENTIAL ROLE IN T 1791 01:32:03,186 --> 01:32:05,488 CELL TRAFFICKING AND FUNCTION BY 1792 01:32:05,488 --> 01:32:06,489 YIELDING T CELL SEQUENCING WHERE 1793 01:32:06,489 --> 01:32:09,726 WE'RE ABLE TO IDENTIFY THE 1794 01:32:09,726 --> 01:32:10,760 SHARED CLONAL TYPE IN THE GUT 1795 01:32:10,760 --> 01:32:13,029 AND ALSO ABLE TO TRACK IT IN THE 1796 01:32:13,029 --> 01:32:18,401 BLOOD AND MORE IMPORTANTLY IN 1797 01:32:18,401 --> 01:32:19,836 THE CNS. 1798 01:32:19,836 --> 01:32:23,406 AND LOOKING AT THE PATIENT WE 1799 01:32:23,406 --> 01:32:26,276 IDENTIFIED THE IT PULSES WHICH 1800 01:32:26,276 --> 01:32:32,048 MEANS THERE'S MORE CELLS IN THE 1801 01:32:32,048 --> 01:32:42,592 CNS COMPARED TO CONTROL AND THE 1802 01:32:43,393 --> 01:32:47,130 INFLAMMATION INCLUDES MACRO 1803 01:32:47,130 --> 01:32:47,464 PHAGE. 1804 01:32:47,464 --> 01:32:52,402 IT'S HIGHLY ENRICHED IN RBD AND 1805 01:32:52,402 --> 01:33:00,110 BD PATIENT WITH THE SIGNATURE 1806 01:33:00,110 --> 01:33:07,751 AND SIMILARLY THE BRAIN 1807 01:33:07,751 --> 01:33:08,451 MACROPHAGE. 1808 01:33:08,451 --> 01:33:13,723 OUR FUTURE DIRECTION IS TO BUILD 1809 01:33:13,723 --> 01:33:15,992 TOOLS TO UNDERSTAND HOW THE 1810 01:33:15,992 --> 01:33:18,461 BRAIN ACCESS CAN CONTRIBUTE OR 1811 01:33:18,461 --> 01:33:19,863 LEAD TO THE INFLAMMATION IN 1812 01:33:19,863 --> 01:33:20,697 PARKINSON'S DISEASE. 1813 01:33:20,697 --> 01:33:24,000 WITH THAT I WOULD LIKE TO THANK 1814 01:33:24,000 --> 01:33:29,606 MY FUNDING AGENCY IN FUNDING MY 1815 01:33:29,606 --> 01:33:35,345 WORK IN THE CENTRAL NERVOUS 1816 01:33:35,345 --> 01:33:40,450 SYSTEM WITH GRANTS FROM NIH AND 1817 01:33:40,450 --> 01:33:42,051 THE PARKINSON'S DISEASE 1818 01:33:42,051 --> 01:33:44,187 FUNDATION FOR FUNDING OUR 1819 01:33:44,187 --> 01:33:45,922 RESEARCH AND THANK MY LAB 1820 01:33:45,922 --> 01:33:49,993 MEMBERS FOR THEIR GREAT EFFORT 1821 01:33:49,993 --> 01:33:53,263 AND FOR LEADING OUR TEAM. 1822 01:33:53,263 --> 01:33:57,734 AS A Ph.D. SCIENTIST OUR HUMAN 1823 01:33:57,734 --> 01:34:00,136 RESEARCH IS BASED ON THE CLOSE 1824 01:34:00,136 --> 01:34:00,703 COLLABORATION WITH OUR TEAM. 1825 01:34:00,703 --> 01:34:10,880 THANK YOU. 1826 01:34:12,715 --> 01:34:22,892 >> THANK YOU. 1827 01:34:25,895 --> 01:34:32,602 >> GOOD MORNING I'M JOSÉ HERRERO 1828 01:34:32,602 --> 01:34:36,439 AT THE FEINSTEIN INSTITUTE OF 1829 01:34:36,439 --> 01:34:39,075 MEDICAL RESEARCH ON PERSISTENT 1830 01:34:39,075 --> 01:34:41,678 DYSPNEA INSIGHTS FROM THE 1831 01:34:41,678 --> 01:34:44,380 INVASIONIVE HUMAN RECORD OF 1832 01:34:44,380 --> 01:34:46,483 RESPIRATORY RELATED BRAIN 1833 01:34:46,483 --> 01:34:48,017 OSCILLATIONS DURING RESPIRATORY 1834 01:34:48,017 --> 01:34:49,752 CHALLENGE AND THIS IS IT WHEN 1835 01:34:49,752 --> 01:34:51,754 YOU FEEL SHORTNESS OF BREATH 1836 01:34:51,754 --> 01:34:56,459 WHEN YOU GO TO THE GYM AND AN 1837 01:34:56,459 --> 01:34:58,862 ARTICLE IN THE NEW YORK TIMES 1838 01:34:58,862 --> 01:35:02,832 THERE WAS A TOMORROW OF SLEEP 1839 01:35:02,832 --> 01:35:05,935 APNEA WHICH AFFECTS TO MOST 1840 01:35:05,935 --> 01:35:08,638 PEOPLE LOOKS AT THE MONITORS FOR 1841 01:35:08,638 --> 01:35:16,045 LONG PERIODS OF TIME. 1842 01:35:16,045 --> 01:35:17,580 THIS BREATH CAUSES SUSPENSION 1843 01:35:17,580 --> 01:35:19,782 PERIODS THAT CAN BEING LONG AND 1844 01:35:19,782 --> 01:35:20,583 FREQUENT AND THE PERSON IS NOT 1845 01:35:20,583 --> 01:35:24,454 AWARE OF THEM. 1846 01:35:24,454 --> 01:35:26,155 IT HAPPENS MORE OFTEN IF YOU 1847 01:35:26,155 --> 01:35:34,831 HAVE A SEDENTARY LIFE. 1848 01:35:34,831 --> 01:35:39,469 TO SPECULATE THE MECHANISMS THAT 1849 01:35:39,469 --> 01:35:42,372 UNDER LIE UNAWARE BREATHE HOLD 1850 01:35:42,372 --> 01:35:44,774 PERIODS WOULD BE FROM DIFFERENT 1851 01:35:44,774 --> 01:35:46,643 AREAS IN THE BRAIN SENDING 1852 01:35:46,643 --> 01:35:49,946 SIGNALS TO TO THE BRAIN 1853 01:35:49,946 --> 01:35:54,317 RESPIRATORY CENTERS SUPPRESSING 1854 01:35:54,317 --> 01:35:56,019 RESPIRATORY SYSTEMS AND REPRESS 1855 01:35:56,019 --> 01:35:58,021 MUSCLES AND RESULT IN BREATH 1856 01:35:58,021 --> 01:36:00,690 HOLD PERIODS. 1857 01:36:00,690 --> 01:36:01,991 THE THIRD CLAIM THIS IS 1858 01:36:01,991 --> 01:36:03,426 SUSTAINED FOR LONG PERIOD OF 1859 01:36:03,426 --> 01:36:07,096 TIME CAN RESULT IN MORE 1860 01:36:07,096 --> 01:36:08,264 PATHOLOGICAL BREATHING 1861 01:36:08,264 --> 01:36:10,767 ABNORMALITIES INCLUDING DYSPNEA. 1862 01:36:10,767 --> 01:36:16,239 WHILE THIS NEEDS TO MORE 1863 01:36:16,239 --> 01:36:19,208 RESEARCH NEEDING TO BE DONE AND 1864 01:36:19,208 --> 01:36:23,646 WE HAVE AN INCREASING INCIDENCE 1865 01:36:23,646 --> 01:36:26,282 OF THOSE BEING DIAGNOSED WITH 1866 01:36:26,282 --> 01:36:28,017 THIS SINCE COVID AND THOSE WHO 1867 01:36:28,017 --> 01:36:30,587 WEAR FACE MASKS FOR A LONG 1868 01:36:30,587 --> 01:36:34,991 PERIOD AND OPIOID USERS AND THE 1869 01:36:34,991 --> 01:36:38,928 OTHER AND THE LUNGS ARE NORMAL 1870 01:36:38,928 --> 01:36:40,396 OR RELATIVELY NORMAL AND THE 1871 01:36:40,396 --> 01:36:42,832 SIGNALS TO THE BRAIN ARE NORMAL 1872 01:36:42,832 --> 01:36:49,606 HOWEVER, THERE IS AN ABNORMAL 1873 01:36:49,606 --> 01:36:53,076 SENSATION OF THE PROCESSING AND 1874 01:36:53,076 --> 01:36:54,043 SUPPRESSES THIS IN THE BRAIN 1875 01:36:54,043 --> 01:36:56,412 STEM AND WE PUBLISHED A PAPER 1876 01:36:56,412 --> 01:36:57,914 AND CHALLENGED THE TRADITIONAL 1877 01:36:57,914 --> 01:36:59,849 VIEW THAT BRAIN STEM CONTROLS 1878 01:36:59,849 --> 01:37:08,958 ALL ASPECTS RESPIRATION AND WE 1879 01:37:08,958 --> 01:37:10,727 FOUND THERE WERE NEURONAL 1880 01:37:10,727 --> 01:37:12,795 EXCITABILITY WITH THE BREATHING 1881 01:37:12,795 --> 01:37:13,796 CYCLE. 1882 01:37:13,796 --> 01:37:24,340 THIS HELPED REFURISH -- THIS WAS 1883 01:37:29,946 --> 01:37:37,987 LOOKING AT RESPIRATORY DISORDERS 1884 01:37:37,987 --> 01:37:40,823 AND HOW THESE GO TO PEOPLE WITH 1885 01:37:40,823 --> 01:37:44,527 BREATHING PROBLEMS SUCH AS 1886 01:37:44,527 --> 01:37:45,228 DYSPNEA. 1887 01:37:45,228 --> 01:37:47,664 THE PRIMARY TREATMENT AND IF 1888 01:37:47,664 --> 01:37:52,602 THAT DOESN'T WORK WHERE HE 1889 01:37:52,602 --> 01:37:54,737 PRESCRIBE OPIOIDS WITH DIFFERENT 1890 01:37:54,737 --> 01:37:57,440 SIDE S AND THEY TARGET THE BRAIN 1891 01:37:57,440 --> 01:37:58,775 RATHER THAN LUNGS SO WHY NOT 1892 01:37:58,775 --> 01:38:01,844 UNDERSTAND WHAT THE BRAIN IS 1893 01:38:01,844 --> 01:38:04,313 DOING AND COME UP WITH 1894 01:38:04,313 --> 01:38:08,117 ALTERNATIVE TO OPIOIDS. 1895 01:38:08,117 --> 01:38:10,820 WE WERE AT THE WARSAW MEETING IN 1896 01:38:10,820 --> 01:38:13,122 2019 WITH A CLEAR MESSAGE. 1897 01:38:13,122 --> 01:38:14,824 WE NEED BETTER TOOLS TO EVALUATE 1898 01:38:14,824 --> 01:38:25,134 THE INTEROCEPTION. 1899 01:38:25,535 --> 01:38:29,772 TOGETHER WITH MY TEAM WE 1900 01:38:29,772 --> 01:38:31,207 COLLABORATED AND THIS WAS DONE 1901 01:38:31,207 --> 01:38:37,046 TO DEVELOP A BETTER MODEL OF 1902 01:38:37,046 --> 01:38:41,017 DYSPNEA AND MAP THE DISEASE AND 1903 01:38:41,017 --> 01:38:46,322 WE USE THE DETECTION TASK AND 1904 01:38:46,322 --> 01:38:49,659 HAVE A BALLOON INFLATED AND WE 1905 01:38:49,659 --> 01:38:50,393 RECORD AND THERE'S AN EXAMPLE 1906 01:38:50,393 --> 01:38:54,097 TRIAL WHERE YOU YOU CAN SEE THE 1907 01:38:54,097 --> 01:38:55,631 MOUTH INCREASING AFTER 1908 01:38:55,631 --> 01:38:57,166 VENTILATION AND INCREASING 1909 01:38:57,166 --> 01:38:58,868 FURTHER WHEN THERE'S AN 1910 01:38:58,868 --> 01:38:59,502 OCCLUSION PERIOD. 1911 01:38:59,502 --> 01:39:09,445 THIS WAS RECORDED WITH THE MOTO 1912 01:39:09,445 --> 01:39:12,448 CORTEX AND THE PRELIMINARY 1913 01:39:12,448 --> 01:39:17,653 RESULTS WE FOUND THIS 1914 01:39:17,653 --> 01:39:18,955 SUPPRESSION IN OSCILLATIONS 1915 01:39:18,955 --> 01:39:21,224 WITHIN THE OCCLUSION TIME FOR CO 1916 01:39:21,224 --> 01:39:23,926 SECONDS AND ENHANCE GAMMA 1917 01:39:23,926 --> 01:39:25,895 OSCILLATIONS AND WAS NOT THE 1918 01:39:25,895 --> 01:39:28,664 FIRST TIME REPORTED THE 1919 01:39:28,664 --> 01:39:31,901 INHALATIONS HAS BEEN RECORDED 1920 01:39:31,901 --> 01:39:33,469 ALSO FOR FINGER MOVEMENT. 1921 01:39:33,469 --> 01:39:38,307 WE'RE LOOKING AT OTHER BRAIN 1922 01:39:38,307 --> 01:39:41,410 AREAS AND MAPPING AND LOOKING AT 1923 01:39:41,410 --> 01:39:44,280 THE COMPONENTS OF DYSPNEA. 1924 01:39:44,280 --> 01:39:47,116 AND WE ARE ASKED TO SAY 1925 01:39:47,116 --> 01:39:48,284 SOMETHING SPERM ABOUT THIS AND 1926 01:39:48,284 --> 01:39:52,555 IN MY FREE TIME I'M A DEEP SEA 1927 01:39:52,555 --> 01:39:55,758 DIVER AND LOVE TO HOLD MY BREATH 1928 01:39:55,758 --> 01:39:56,459 UNDER WATER AND CATCH FISH. 1929 01:39:56,459 --> 01:40:01,664 >> THANK YOU. 1930 01:40:01,664 --> 01:40:04,333 >> HOW TO OUR WONDERFUL 1931 01:40:04,333 --> 01:40:04,767 SPEAKERS. 1932 01:40:04,767 --> 01:40:07,136 THIS SESSION IS ADJOURNED. 1933 01:40:07,136 --> 01:40:09,038 WE'LL HAVE 15 MINUTES BREAK AND 1934 01:40:09,038 --> 01:40:13,142 POSTER SET UP IN THE CABINET 1935 01:40:13,142 --> 01:40:13,976 ROOM. 1936 01:40:13,976 --> 01:40:15,912 PLEASE COME BACK AT 10:50 FOR 1937 01:40:15,912 --> 01:40:21,887 THENEXT SESSION. 1938 01:40:21,887 --> 01:40:22,388 ALL RIGHT. 1939 01:40:22,388 --> 01:40:25,825 I'D LIKE TO WELCOME EVERYONE TO 1940 01:40:25,825 --> 01:40:36,268 SESSION 2, TECHNOLOGY AND 1941 01:40:37,970 --> 01:40:43,342 TRANSLATION , REVERSE 1942 01:40:43,342 --> 01:40:45,878 TRANSLATION AND INFECTION 1943 01:40:45,878 --> 01:40:47,313 RESEARCH AND I'M TODD HOROWITZ 1944 01:40:47,313 --> 01:40:48,881 AND WE HAVE AN EXCELLENT LINEUP 1945 01:40:48,881 --> 01:40:51,484 FOR YOU TODAY AND I'M GOING TURN 1946 01:40:51,484 --> 01:40:56,822 THE PODIUM TO OLGA TO INTRODUCE 1947 01:40:56,822 --> 01:40:57,790 OUR LINEUP OF DISTINGUISHED 1948 01:40:57,790 --> 01:41:04,764 SPEAKERS. 1949 01:41:04,764 --> 01:41:05,598 >> THANK YOU. 1950 01:41:05,598 --> 01:41:07,800 IT'S A TINY STAGE SO I HOPE NO 1951 01:41:07,800 --> 01:41:08,200 ONE FALLS. 1952 01:41:08,200 --> 01:41:10,202 IT'S A PLEASURE TO BE HERE AND 1953 01:41:10,202 --> 01:41:13,172 WONDERFUL TO SEE EVERYONE IN THE 1954 01:41:13,172 --> 01:41:13,372 ROOM. 1955 01:41:13,372 --> 01:41:15,107 IT'S TERRIFIC. 1956 01:41:15,107 --> 01:41:20,846 ANY JOB IS TO INTRODUCING THIS 1957 01:41:20,846 --> 01:41:25,818 SPEAKER LIST THIS MORNING OUR 1958 01:41:25,818 --> 01:41:30,122 FIRST TALK WILL BE FROM KARL 1959 01:41:30,122 --> 01:41:32,792 DEISSEROTH FROM STANFORD 1960 01:41:32,792 --> 01:41:35,361 UNIVERSITY AND THEN SAHIB KHALSA 1961 01:41:35,361 --> 01:41:38,664 LOOKING AT THE PER TUSHING THE 1962 01:41:38,664 --> 01:41:46,138 RHYTHMS WITHIN CARDIORESPIRATORY 1963 01:41:46,138 --> 01:41:51,977 AND GASTROINTESTINAL INSIGHT AND 1964 01:41:51,977 --> 01:41:54,113 THEN TODD COLEMAN ADVANCING THE 1965 01:41:54,113 --> 01:41:56,816 METHODS OF TECHNOLOGIES TO 1966 01:41:56,816 --> 01:41:57,983 MONITOR MODULATE COUPLINGS 1967 01:41:57,983 --> 01:42:00,553 BETWEEN THE HUMAN BRAIN STOMACH 1968 01:42:00,553 --> 01:42:03,389 AND THEN DANA SMALL AND FINAL IS 1969 01:42:03,389 --> 01:42:05,825 BY SARAH GARFINKEL FROM 1970 01:42:05,825 --> 01:42:15,267 UNIVERSITY OF COLLEGE LONDON 1971 01:42:15,267 --> 01:42:17,069 TALKING ABOUT CARDIAC 1972 01:42:17,069 --> 01:42:23,843 INTEROCEPTIVE TRAINING ENHANCES 1973 01:42:23,843 --> 01:42:26,712 INSULA CONNECTIVITY AND REDUCES 1974 01:42:26,712 --> 01:42:36,355 ANXIETY. 1975 01:42:36,355 --> 01:42:39,925 >> THANK YOU FOR THE INVITATION 1976 01:42:39,925 --> 01:42:40,693 AND INTRODUCTION AND ORGANIZING 1977 01:42:40,693 --> 01:42:42,027 THE GREAT MEETING. 1978 01:42:42,027 --> 01:42:43,195 I'VE ENJOYED IT SO FAR. 1979 01:42:43,195 --> 01:42:47,533 I WANT TO SHARE THIS HAS BEEN A 1980 01:42:47,533 --> 01:42:49,935 REAL INTERESTING JOURNEY TO GET 1981 01:42:49,935 --> 01:42:50,569 TO THIS POINT. 1982 01:42:50,569 --> 01:42:53,539 I FIRST BECAME INTERESTED IN 1983 01:42:53,539 --> 01:42:55,708 INTEROCEPTION AS A PSYCHIATRY 1984 01:42:55,708 --> 01:42:57,276 RESIDENT WHEN WE WERE TAUGHT IF 1985 01:42:57,276 --> 01:42:59,512 SOMEONE COMES TO YOU WITH A 1986 01:42:59,512 --> 01:43:00,246 PANIC DISORDER YOU HAVE TO THINK 1987 01:43:00,246 --> 01:43:02,114 ABOUT THEIR HEART AND THERE'S A 1988 01:43:02,114 --> 01:43:05,918 SIGNIFICANT FRACTION OF PEOPLE 1989 01:43:05,918 --> 01:43:09,488 WHO WILL HAVE A PRIMARY DISORDER 1990 01:43:09,488 --> 01:43:12,491 OF ARRHYTHMIAS AND THAT ALWAYS 1991 01:43:12,491 --> 01:43:14,760 INTRIGUES ME. 1992 01:43:14,760 --> 01:43:16,161 HOW COULD A CARDIAC PROBLEM LEAD 1993 01:43:16,161 --> 01:43:26,605 TO A PSYCHIATRIC DISORDER. 1994 01:43:29,975 --> 01:43:35,080 THE INTEROCEPTION OF OUR WORK 1995 01:43:35,080 --> 01:43:35,681 ALLOWED US TO MAKE HEADWAY ON 1996 01:43:35,681 --> 01:43:43,756 THE QUESTION. 1997 01:43:43,756 --> 01:43:48,894 THE PROTEINS WERE NOT WHAT YOU 1998 01:43:48,894 --> 01:43:51,597 MIGHT LIKE AND I WANTED TO SHARE 1999 01:43:51,597 --> 01:43:53,465 ON THE GENES BECAUSE IT WAS 2000 01:43:53,465 --> 01:43:55,868 CRITICAL TO MAKE THE HEADWAY AND 2001 01:43:55,868 --> 01:43:58,404 IT'S A BIG FAMILY. 2002 01:43:58,404 --> 01:44:04,677 THE GREEN BLOB IS THE PUMPS 2003 01:44:04,677 --> 01:44:08,380 PROTONS DISCOVERED IN 1970. 2004 01:44:08,380 --> 01:44:18,891 FAST FORWARD A LITTLE BIT AND WE 2005 01:44:18,891 --> 01:44:29,401 DISCOVERED CHANNEL RHODOPSIN. 2006 01:44:35,307 --> 01:44:41,213 AND A FEW YEARS AFTER THAT FROM 2007 01:44:41,213 --> 01:44:43,048 THIS LITTLE ORGANISM WHERE HE 2008 01:44:43,048 --> 01:44:45,217 FOUND OUT WHAT TURNED TO BE A 2009 01:44:45,217 --> 01:44:47,319 LARGER FAMILY AND THIS ALLOWED 2010 01:44:47,319 --> 01:44:49,622 US TO MAKE THE HEADWAY WE WERE 2011 01:44:49,622 --> 01:44:51,657 HOPING TO MAKE ON THIS QUESTION 2012 01:44:51,657 --> 01:44:57,496 OF INTERACTION BETWEEN CARDIAC 2013 01:44:57,496 --> 01:45:01,934 AND PSYCHIATRIC STATES. 2014 01:45:01,934 --> 01:45:12,478 WHAT MADE CHRMINE IN RESPONSE TO 2015 01:45:14,279 --> 01:45:19,451 SHORTER POWER DENSITIES THAN THE 2016 01:45:19,451 --> 01:45:28,861 OTHER AND LOOK AT HOLEGRAPHIC 2017 01:45:28,861 --> 01:45:30,829 METHODS IN 2020 RICHIE CHAN 2018 01:45:30,829 --> 01:45:32,698 STARTED HIS LAB AT UCSF. 2019 01:45:32,698 --> 01:45:35,401 HE FOUND THIS WAS SO SENSITIVE 2020 01:45:35,401 --> 01:45:37,436 YOU COULD ACTIVATE DEEP BRAIN 2021 01:45:37,436 --> 01:45:39,238 NEURONS WITH HIGH TEMPORAL 2022 01:45:39,238 --> 01:45:43,108 RESOLUTION WITH COMPLETELY 2023 01:45:43,108 --> 01:45:44,376 NONINVASIVE LIGHT DELIVERY AND 2024 01:45:44,376 --> 01:45:45,077 SKULL FIBER. 2025 01:45:45,077 --> 01:45:47,579 WE FOLLOWED THAT UP WITH WORK 2026 01:45:47,579 --> 01:45:53,919 ABOUT A YEAR AGO FROM THE LAB 2027 01:45:53,919 --> 01:45:55,454 SHOWING YOU COULD CONTINUE THIS 2028 01:45:55,454 --> 01:45:56,989 THREAD AND KEEP YOUR LIGHT 2029 01:45:56,989 --> 01:46:02,995 SOURCE OUTSIDE THE BODY, THE 2030 01:46:02,995 --> 01:46:08,400 SKULL EVEN AND CAN DO 2031 01:46:08,400 --> 01:46:10,803 OPTOTAGGING AND DRIVING A CELL 2032 01:46:10,803 --> 01:46:13,372 AND JUST REPORTING WITH AN 2033 01:46:13,372 --> 01:46:21,480 ELECTRODE AND TURNED OUT TO BE 2034 01:46:21,480 --> 01:46:23,916 USEFUL RELYING ON A POTENT SET 2035 01:46:23,916 --> 01:46:26,318 OF PROPERTIES CHRMINE HAD. 2036 01:46:26,318 --> 01:46:29,321 AND WHAT WE DESCRIBED WITH 2037 01:46:29,321 --> 01:46:31,724 RICHIE AND A NEUROSURGERY 2038 01:46:31,724 --> 01:46:32,925 RESIDENT AND A GRADUATE STUDENT 2039 01:46:32,925 --> 01:46:34,893 AT THE LAB AT THE TIME ALLOWED 2040 01:46:34,893 --> 01:46:37,296 US TO ADDRESS THIS INTERESTING 2041 01:46:37,296 --> 01:46:39,698 AND THORNY QUESTION THAT OTHERS 2042 01:46:39,698 --> 01:46:41,266 HAD THOUGHT ABOUT AND 2043 01:46:41,266 --> 01:46:42,668 ARTICULATED FOR A LONG TIME 2044 01:46:42,668 --> 01:46:45,237 WHICH GETS TO THE NATURE OF THE 2045 01:46:45,237 --> 01:46:45,804 EMOTION. 2046 01:46:45,804 --> 01:46:48,240 HE WAS ABLE TO ARTICULATE AN 2047 01:46:48,240 --> 01:46:49,241 INTERESTING IDEA WHICH THE 2048 01:46:49,241 --> 01:46:51,210 PEOPLE IN THE ROOM ARE FAMILIAR 2049 01:46:51,210 --> 01:46:54,880 WITH WHICH IS IF YOU REMOVE THE 2050 01:46:54,880 --> 01:46:56,315 BODILY SENSATIONS, WOULD YOU 2051 01:46:56,315 --> 01:46:58,484 REALLY STILL HAVE AN EMOTION 2052 01:46:58,484 --> 01:46:59,318 LEFT AT ALL. 2053 01:46:59,318 --> 01:47:01,920 HE WAS OF THE OPINION YOU 2054 01:47:01,920 --> 01:47:05,023 WOULDN'T. 2055 01:47:05,023 --> 01:47:10,295 THIS WAS HARD TO TEST PRECISELY 2056 01:47:10,295 --> 01:47:14,533 BECAUSE IT WAS HARD TO CAUSE THE 2057 01:47:14,533 --> 01:47:18,804 BODILY FUNCTIONS IN A CLEAN WAY 2058 01:47:18,804 --> 01:47:20,072 AND YOU CAN HAVE SOMETHING BUT 2059 01:47:20,072 --> 01:47:23,675 IT COULD AFFECT THE NEURONS AND 2060 01:47:23,675 --> 01:47:25,477 ENDOTHELIUM AND OTHER PROFESSORS 2061 01:47:25,477 --> 01:47:29,181 AND ELECTRODES DRIVE NEURONS AND 2062 01:47:29,181 --> 01:47:31,717 THE CARDIO MYOCYTES AND THEY 2063 01:47:31,717 --> 01:47:34,253 FIGURED OUT HOW TO ADMINISTER 2064 01:47:34,253 --> 01:47:37,289 CHRMINE THROUGH A PROMOTER TO 2065 01:47:37,289 --> 01:47:39,158 GET EXPRESSION THROUGH THE 2066 01:47:39,158 --> 01:47:39,725 VENTRICULAR WALL, THE MOUSE 2067 01:47:39,725 --> 01:47:45,364 HEART. 2068 01:47:45,364 --> 01:47:48,267 BECAUSE OF THE SENSITIVITY WE 2069 01:47:48,267 --> 01:47:49,935 CAN DRIVE THE HEART RATE AT 2070 01:47:49,935 --> 01:47:51,203 LEVELS THAT WE WANTED. 2071 01:47:51,203 --> 01:47:56,375 WE COULD USE A PSYCH THAT WILL 2072 01:47:56,375 --> 01:47:57,943 DIDN'T CAUSE HEATING BUT COULD 2073 01:47:57,943 --> 01:48:00,012 TAKE THEM FROM THE BASAL HEART 2074 01:48:00,012 --> 01:48:03,081 RATE UP TO 800 OR 900 BEATS PER 2075 01:48:03,081 --> 01:48:04,016 MINUTE RELIABLY. 2076 01:48:04,016 --> 01:48:09,121 THE FIRST THING WE ASKED WAS DID 2077 01:48:09,121 --> 01:48:14,526 THE MOUSE CARE THIS WAS 2078 01:48:14,526 --> 01:48:15,227 HAPPENING. 2079 01:48:15,227 --> 01:48:18,931 AND WE TEST THE REAL TIME PLACE 2080 01:48:18,931 --> 01:48:21,500 REFERENCE TEST AND MOVE FREELY 2081 01:48:21,500 --> 01:48:28,307 FROM CHAMBER TO CHAMBER AND ONLY 2082 01:48:28,307 --> 01:48:37,049 RECEIVES STIMULATION IN ONE 2083 01:48:37,049 --> 01:48:45,390 CHAMBER. 2084 01:48:45,390 --> 01:48:48,827 THERE WAS NO PREFERENCE AND 2085 01:48:48,827 --> 01:48:50,796 THERE WAS AN EFFECT. 2086 01:48:50,796 --> 01:48:56,235 THE NORMAL PREFERENCE FOR THE 2087 01:48:56,235 --> 01:48:58,637 CLOSED ARMS WAS PHASED WITH THE 2088 01:48:58,637 --> 01:48:59,771 CHRMINE BASED APPROACH. 2089 01:48:59,771 --> 01:49:01,907 AND SIMILARLY IN A TASK WHERE 2090 01:49:01,907 --> 01:49:04,009 THERE'S A VERY SMALL RISK OF 2091 01:49:04,009 --> 01:49:13,418 GETTING A SHOCK IF A THIRSTY 2092 01:49:13,418 --> 01:49:15,087 MOUSE DRINKS WATER IT DOESN'T 2093 01:49:15,087 --> 01:49:19,892 ATTEMPT THE SPEED BUT THE HEART 2094 01:49:19,892 --> 01:49:21,526 WAS BEING PACED IT DID AFFECT 2095 01:49:21,526 --> 01:49:27,966 THE LATENCY WITH WHICH THE MAN 2096 01:49:27,966 --> 01:49:29,768 WOULD GO OR THE RISK. 2097 01:49:29,768 --> 01:49:35,140 SO APPREHENSION IN THE RISK OF 2098 01:49:35,140 --> 01:49:36,341 IMMEDIATE THREAT AND WE WERE 2099 01:49:36,341 --> 01:49:37,175 CURIOUS HOW THIS WOULD BE 2100 01:49:37,175 --> 01:49:44,716 MANIFESTED IN THE BRAIN. 2101 01:49:44,716 --> 01:49:46,285 I'LL HIGHLIGHT INTERESTING 2102 01:49:46,285 --> 01:49:47,552 FINDING. 2103 01:49:47,552 --> 01:49:53,625 WE LOOKED THE BRAIN USING 2104 01:49:53,625 --> 01:49:54,192 GENE-BASED SCREEN AND MANY 2105 01:49:54,192 --> 01:49:57,829 REGIONS WERE NOT AFFECTED AND 2106 01:49:57,829 --> 01:50:07,172 VISUALLY AUDITORY AND PREFRONTAL 2107 01:50:07,172 --> 01:50:09,508 DIFFERENCES SEEING AN INSULA 2108 01:50:09,508 --> 01:50:15,514 PROMINENCE CHANGES IN RESPONSE 2109 01:50:15,514 --> 01:50:18,550 TO CARDIAC PACING. 2110 01:50:18,550 --> 01:50:21,586 WE WANTED TO SEE WHICH CHANGES 2111 01:50:21,586 --> 01:50:24,690 MATTERED AND WE SAW THEY WERE 2112 01:50:24,690 --> 01:50:27,526 ACTIVATED DIDN'T KNOW THEY WERE 2113 01:50:27,526 --> 01:50:29,361 CAUSALLY RELATIVE TO A STATE 2114 01:50:29,361 --> 01:50:29,594 CHANGE. 2115 01:50:29,594 --> 01:50:31,396 AND WE WANTED TO DO LOSS OF 2116 01:50:31,396 --> 01:50:33,899 FUNCTION IN THOSE BRAIN REGIONS 2117 01:50:33,899 --> 01:50:36,034 AND SEE WHICH WAS IMPORTANT. 2118 01:50:36,034 --> 01:50:41,707 WE WERE ABLE TO MAKE CONDUCTED 2119 01:50:41,707 --> 01:50:45,143 OPTIONS AND A CHLORIDE RHODOPSIN 2120 01:50:45,143 --> 01:50:49,448 WAS THE ONE WE WENT FOR TO USE 2121 01:50:49,448 --> 01:50:53,518 AND WE HAD A TUBE PACING THE 2122 01:50:53,518 --> 01:50:55,988 HEART WITH CHRMINE AND 2123 01:50:55,988 --> 01:50:59,391 INHIBITING DIFFERENT BRAIN 2124 01:50:59,391 --> 01:51:01,927 REGIONS WITH THIS RHODOPSIN AND 2125 01:51:01,927 --> 01:51:03,895 JUST TO SAY THAT'S THE ESSENCE 2126 01:51:03,895 --> 01:51:09,501 OF THE EXPERIMENT AND TESTED 2127 01:51:09,501 --> 01:51:20,412 INHIBITI IING PREFRONTAL OR INSR 2128 01:51:27,719 --> 01:51:31,757 CORTEX AND DID NOT SEE THAT 2129 01:51:31,757 --> 01:51:33,058 EFFECT WITH THE MEDIAL 2130 01:51:33,058 --> 01:51:35,627 PREFRONTAL CORTEX. 2131 01:51:35,627 --> 01:51:39,431 NOT TO SAY PREFRONTAL CORTEX 2132 01:51:39,431 --> 01:51:41,600 ISN'T INVOLVED BUT ON THE TIME 2133 01:51:41,600 --> 01:51:43,869 SCALE WE DIDN'T SEE AN EFFECT 2134 01:51:43,869 --> 01:51:46,571 WHEREAS WE DID SEE IT WITH 2135 01:51:46,571 --> 01:51:46,805 INSULA. 2136 01:51:46,805 --> 01:51:48,140 THAT WAS INTERESTING. 2137 01:51:48,140 --> 01:51:50,876 WE CAN POINT TO THE INSULA 2138 01:51:50,876 --> 01:51:53,845 MEDIATING ASPECT OF THE 2139 01:51:53,845 --> 01:51:55,680 REPRESENTATIVES. 2140 01:51:55,680 --> 01:51:58,984 AND WE HAVE TO WONDER -- AND I 2141 01:51:58,984 --> 01:52:05,690 THINK THE PREFRONTAL CORTEX WAS 2142 01:52:05,690 --> 01:52:16,234 INTERESTING AND YOU SAY MAYBE WE 2143 01:52:17,969 --> 01:52:21,406 COULDN'T CONTROL ENOUGH OF 2144 01:52:21,406 --> 01:52:23,108 PREFRONTAL CORTEX ENOUGH WITH 2145 01:52:23,108 --> 01:52:23,442 POTENCY. 2146 01:52:23,442 --> 01:52:26,311 AND I WANTED TO SHARE OUR NEW 2147 01:52:26,311 --> 01:52:29,915 TOOLS THAT MAY HELP ADDRESS 2148 01:52:29,915 --> 01:52:34,419 QUESTIONS LIKE THIS ININCRECREA 2149 01:52:34,419 --> 01:52:38,490 VIRG VIGOR AND POTENCY. 2150 01:52:38,490 --> 01:52:42,294 MAYBE SOMETHING WAS MISSING. 2151 01:52:42,294 --> 01:52:43,462 MAYBE THE PREFRONTAL CORTEX 2152 01:52:43,462 --> 01:52:45,330 ISN'T INVOLVED OR IS AND WE'RE 2153 01:52:45,330 --> 01:52:45,730 MISSING IT. 2154 01:52:45,730 --> 01:52:49,301 COULD IT BE WE DON'T HAVE ENOUGH 2155 01:52:49,301 --> 01:52:51,503 SPATIAL EXTENT OR NOT OPERATING 2156 01:52:51,503 --> 01:52:52,604 ON LONG ENOUGH TIME SCALES FOR 2157 01:52:52,604 --> 01:52:57,275 THIS TO BE RELEVANT? 2158 01:52:57,275 --> 01:53:03,515 NOW, WE'VE BEEN WORKING ON 2159 01:53:03,515 --> 01:53:04,382 CHANNELRHODOPSIN PROPERTY TO 2160 01:53:04,382 --> 01:53:07,352 MAKE SURE WE CAN ACCESS THE 2161 01:53:07,352 --> 01:53:10,622 REGIMES OF BEHAVIORAL 2162 01:53:10,622 --> 01:53:11,323 INTERVENTION. 2163 01:53:11,323 --> 01:53:14,759 WE'VE BEEN MAKING 2164 01:53:14,759 --> 01:53:16,761 CHANNELRHODOPSIN'S INHIBITORY 2165 01:53:16,761 --> 01:53:18,296 AND OPERATE ON LONG TIME SCALES. 2166 01:53:18,296 --> 01:53:24,002 A COUPLE MUTATIONS THE C128 AND 2167 01:53:24,002 --> 01:53:28,173 D156 RESIDUES AROUND THE RING 2168 01:53:28,173 --> 01:53:31,843 SHOWN IN ORANGE WE SHOWED WE CAN 2169 01:53:31,843 --> 01:53:36,214 CREATE RHODOPSIN'S WITH LONG 2170 01:53:36,214 --> 01:53:39,384 PHOTO CURRENTS AFTER A LONG 2171 01:53:39,384 --> 01:53:41,786 PULSE OF LIFE AND CAN HAVE 2172 01:53:41,786 --> 01:53:43,388 EFFECTS OF 10 MINUTES OR MORE 2173 01:53:43,388 --> 01:53:44,756 AND THOSE ARE ILLUSTRATED HERE. 2174 01:53:44,756 --> 01:53:49,594 THIS IS AN INHIBITORY VERSION 2175 01:53:49,594 --> 01:53:56,434 MADE OF CHANNELRHODOPSIN AND 2176 01:53:56,434 --> 01:53:58,403 FLASH IT WITH ANOTHER LIGHT. 2177 01:53:58,403 --> 01:54:02,807 WE DID THIS WITH THE CANONICAL 2178 01:54:02,807 --> 01:54:05,911 CHANNELRHODOPSIN BUT THE CHRMINE 2179 01:54:05,911 --> 01:54:07,279 FAMILY WITH HIGHLIGHT 2180 01:54:07,279 --> 01:54:10,415 SENSITIVITY PROPERTIES AND WITH 2181 01:54:10,415 --> 01:54:14,219 CHANNEL RHODOPSIN AND WE ALWAYS 2182 01:54:14,219 --> 01:54:17,155 WANTED TO CREATE AN INHIBITORY 2183 01:54:17,155 --> 01:54:18,356 VERSION OF CHRMINE AND WE WERE 2184 01:54:18,356 --> 01:54:21,893 NEVER ABLE TO DO IT. 2185 01:54:21,893 --> 01:54:23,428 WE KNEW THE MODIFICATIONS TO 2186 01:54:23,428 --> 01:54:33,972 CHANGE THE CHANNELRHODOPSIN AND 2187 01:54:39,177 --> 01:54:40,946 THIS IS A TOOL WHERE WE USED THE 2188 01:54:40,946 --> 01:54:43,648 HIGH RESOLUTION STRUCTURE OF 2189 01:54:43,648 --> 01:54:46,484 CHRMINE TO CREATE RS CHRMINE. 2190 01:54:46,484 --> 01:54:48,887 TO THE WERE ABLE TO SLIGHTLY 2191 01:54:48,887 --> 01:54:49,921 SHIFT IT TO THE RED BUT ON THE 2192 01:54:49,921 --> 01:54:52,224 LEFT YOU CAN SEE THE PROMINENT 2193 01:54:52,224 --> 01:54:53,425 REDUCTION OF THE BLUE WHICH IS 2194 01:54:53,425 --> 01:54:56,428 USEFUL FOR INTEGRATING IT 2195 01:54:56,428 --> 01:54:58,597 TOGETHER IN THE BLUE LIGHT 2196 01:54:58,597 --> 01:55:01,266 ACTIVATED READOUTS LIKE CALCIUM 2197 01:55:01,266 --> 01:55:01,566 INDICATORS. 2198 01:55:01,566 --> 01:55:04,703 WE HAD A GOOD STRUCTURE AND WERE 2199 01:55:04,703 --> 01:55:06,972 GOOD AT ENGINEERING CHRMINE BUT 2200 01:55:06,972 --> 01:55:09,507 WEREN'T ABLE TO MAKE AN 2201 01:55:09,507 --> 01:55:11,376 INHIBITORY CHRMINE BUT MADE A 2202 01:55:11,376 --> 01:55:11,910 LONG ACTING. 2203 01:55:11,910 --> 01:55:14,512 AND WHAT TURNED OUT TO BE USEFUL 2204 01:55:14,512 --> 01:55:15,714 WERE OTHER MEMBERS OF THE PINK 2205 01:55:15,714 --> 01:55:21,720 FAMILY ON THE LEFT. 2206 01:55:21,720 --> 01:55:25,724 I MENTIONED CHRMINE LED US TO 2207 01:55:25,724 --> 01:55:28,994 UNDERSTAND THIS BRANCH OF THE 2208 01:55:28,994 --> 01:55:33,565 CHRMINE TREE AND IT'S ALSO 2209 01:55:33,565 --> 01:55:34,566 SELECTIVE. 2210 01:55:34,566 --> 01:55:36,067 CANONICAL CHANNEL REDUCTIONS 2211 01:55:36,067 --> 01:55:45,610 WITH MAGNESIUM AND PROTONS AND 2212 01:55:45,610 --> 01:55:48,813 IT'S INTERESTING AND WE'RE 2213 01:55:48,813 --> 01:55:52,751 WORKING ON FIGURING THIS OUT AND 2214 01:55:52,751 --> 01:55:53,918 A GROUP FOUND OUT LATER THERE'S 2215 01:55:53,918 --> 01:55:58,189 ANOTHER BRANCH OF THIS FAMILY 2216 01:55:58,189 --> 01:56:05,964 THE POTASSIUM CHANNEL REDUCTING 2217 01:56:05,964 --> 01:56:07,866 CHANNELS AND INTERESTING SUB 2218 01:56:07,866 --> 01:56:12,837 BRANCH OF THE FAMILY. 2219 01:56:12,837 --> 01:56:21,479 THEY WEREN'T PERFECT. 2220 01:56:21,479 --> 01:56:25,183 THE MINUS 65 IS IN THE RIGHT 2221 01:56:25,183 --> 01:56:25,450 DIRECTION. 2222 01:56:25,450 --> 01:56:29,921 WE DESCRIBED THE STRUCTURE OF 2223 01:56:29,921 --> 01:56:31,156 THE POTASSIUM CHANNELRHODOPSIN 2224 01:56:31,156 --> 01:56:33,925 STRUCTURE TO MODIFY THEM AND THE 2225 01:56:33,925 --> 01:56:35,126 STRUCTURE CRITICAL GETTING US TO 2226 01:56:35,126 --> 01:56:36,561 THE POINT TO MAKE THE 2227 01:56:36,561 --> 01:56:37,829 MODIFICATIONS WE WANTED AND FOR 2228 01:56:37,829 --> 01:56:39,130 THE SAKE OF TIME I WON'T GO INTO 2229 01:56:39,130 --> 01:56:44,402 ALL THE DETAILS BUT TO SAY KCRs 2230 01:56:44,402 --> 01:56:54,579 LIKE CHRMINE ARE TRIMERS AND OUR 2231 01:56:54,579 --> 01:56:58,783 EFFORTS WE FOUND FOUND A 2232 01:56:58,783 --> 01:57:00,919 POTASSIUM FILTERING STRUCTURE 2233 01:57:00,919 --> 01:57:09,494 DIFFERENT FROM THE TETROMERIC 2234 01:57:09,494 --> 01:57:12,263 FEATURE SOME ARE LAID OUT. 2235 01:57:12,263 --> 01:57:17,669 THERE'S NO FOURFOLD SYMMETRY BUT 2236 01:57:17,669 --> 01:57:19,404 THE MUTANT IMPROVES IT AND GETS 2237 01:57:19,404 --> 01:57:23,208 IT DOWN TO MINUS 500 WHICH IS 2238 01:57:23,208 --> 01:57:24,509 QUITE A DIFFERENCE AND WE WERE 2239 01:57:24,509 --> 01:57:25,510 ABLE TO MAKE LONG ACTING 2240 01:57:25,510 --> 01:57:27,879 VERSIONS OF THIS. 2241 01:57:27,879 --> 01:57:29,481 THERE'S A SIMILAR PLOT 2242 01:57:29,481 --> 01:57:35,186 UNPUBLISHED BUT YOU CAN SEE THE 2243 01:57:35,186 --> 01:57:39,491 K1CTs AND POTASSIUM RHODOPSINS 2244 01:57:39,491 --> 01:57:41,459 AND HAVE A HUGE PHOTO CURRENT 2245 01:57:41,459 --> 01:57:43,261 AND SEE THE ONE, TWO AND THREE 2246 01:57:43,261 --> 01:57:46,431 NANO AMPS AND THE LONG ACTING 2247 01:57:46,431 --> 01:57:48,233 ASPECT IN TERMS OF SECONDS HERE. 2248 01:57:48,233 --> 01:57:54,639 THAT'S WHAT WE WANTED. 2249 01:57:54,639 --> 01:57:57,509 LOOKING FORWARD WE'RE MAKING 2250 01:57:57,509 --> 01:58:04,482 MOUSE LINES AND MADE CHRMINE 2251 01:58:04,482 --> 01:58:07,318 COMBINANT DEPENDENT MOUSE LINES 2252 01:58:07,318 --> 01:58:12,690 AND MAKING CALCIUM MOUSE LINES 2253 01:58:12,690 --> 01:58:14,959 AND ACTIVATED INHIBITORS AND 2254 01:58:14,959 --> 01:58:16,361 HAPPY TO SHARE THOSE AS SOON AS 2255 01:58:16,361 --> 01:58:16,828 THEY'RE READY. 2256 01:58:16,828 --> 01:58:18,196 I'LL WRAP UP THERE. 2257 01:58:18,196 --> 01:58:20,265 I THINK SOME OF THESE TOOLS 2258 01:58:20,265 --> 01:58:21,366 MAYBE USEFUL FOR A BROAD 2259 01:58:21,366 --> 01:58:22,634 DIVERSITY OF PROJECTS IN THIS 2260 01:58:22,634 --> 01:58:22,934 ROOM. 2261 01:58:22,934 --> 01:58:26,204 WE THINK ABOUT BRAIN-BODY 2262 01:58:26,204 --> 01:58:29,340 INTERACTION AND THINK LARGE 2263 01:58:29,340 --> 01:58:30,775 REGIONS AND SENSITIVITY AND LONG 2264 01:58:30,775 --> 01:58:32,177 ACTING EFFECTS MAY BE USEFUL. 2265 01:58:32,177 --> 01:58:36,314 I WANT TO HIGHLIGHT OUR AMAZING 2266 01:58:36,314 --> 01:58:39,050 COLLEAGUES AND EVERYBODY ELSE 2267 01:58:39,050 --> 01:58:39,551 ALONG THE WAY. 2268 01:58:39,551 --> 01:58:49,928 THANKS FOR YOUR TIME. 2269 01:58:51,596 --> 01:58:52,797 >> THANK YOU FOR THAT TERRIFIC 2270 01:58:52,797 --> 01:58:52,997 TALK. 2271 01:58:52,997 --> 01:58:58,903 MAIN WE CAN TAKE ONE QUESTION. 2272 01:58:58,903 --> 01:59:01,339 ARE THERE ANY BURNING QUESTIONS? 2273 01:59:01,339 --> 01:59:02,907 DO YOU MIND SPEAKING TO THE 2274 01:59:02,907 --> 01:59:13,251 MICROPHONE, PLEASE. 2275 01:59:15,920 --> 01:59:17,288 >> THANK YOU. 2276 01:59:17,288 --> 01:59:20,525 I'M A FELLOW AT CHILDREN'S 2277 01:59:20,525 --> 01:59:27,832 HOSPITAL AND LOOKING AT 2278 01:59:27,832 --> 01:59:32,103 NATURALLY OCCURRING RHODOPSINS 2279 01:59:32,103 --> 01:59:35,340 THEY'RE TRANS MEMBRANE PROTEINS 2280 01:59:35,340 --> 01:59:39,344 AND I WANTED TO KNOW WHAT IS 2281 01:59:39,344 --> 01:59:44,148 YOUR PERSPECTIVE ON NATURALLY 2282 01:59:44,148 --> 01:59:47,852 OCCURRING RHODOPSIN AND HOW THEY 2283 01:59:47,852 --> 01:59:48,319 GO THROUGH CHANNELS. 2284 01:59:48,319 --> 01:59:50,288 >> HERE I WOULD DRAW THE 2285 01:59:50,288 --> 01:59:52,123 DISTINCTION BETWEEN THE DIRECT 2286 01:59:52,123 --> 01:59:56,961 ION CHANNEL RESPONSIVE ONES AND 2287 01:59:56,961 --> 02:00:01,633 THE ONES THAT SIGNAL THE 2288 02:00:01,633 --> 02:00:01,900 CASCADES. 2289 02:00:01,900 --> 02:00:02,767 THE INTERESTING ASPECT ABOUT THE 2290 02:00:02,767 --> 02:00:05,904 WEDNESDAY YOU MENTIONED ARE 2291 02:00:05,904 --> 02:00:09,908 TYPICALLY THE TYPE 2 RHODOPSINS 2292 02:00:09,908 --> 02:00:11,142 CAN BE VERY SENSITIVE BECAUSE 2293 02:00:11,142 --> 02:00:15,580 THEY COUPLE TO THE CASCADES. 2294 02:00:15,580 --> 02:00:17,415 THERE'S AMPLIFICATION AND THAT'S 2295 02:00:17,415 --> 02:00:19,584 ANOTHER WAY TO GO IF YOU'RE 2296 02:00:19,584 --> 02:00:23,254 INTERESTED IN HIGH POTENCY 2297 02:00:23,254 --> 02:00:24,389 RELATIVE TO PHOTONS. 2298 02:00:24,389 --> 02:00:28,393 DOWN SIDE IS YOU LOSE TEMPORAL 2299 02:00:28,393 --> 02:00:31,529 RESOLUTION AND YOU DEPEND ON 2300 02:00:31,529 --> 02:00:35,333 NATIVE COMPONENTS OF THE 2301 02:00:35,333 --> 02:00:36,634 PATHWAY AND YOU CAN GET SIGN 2302 02:00:36,634 --> 02:00:40,305 FLIPS THAT COULD HAPPEN. 2303 02:00:40,305 --> 02:00:47,145 SO DEFINITELY WORTH EXPLORING. 2304 02:00:47,145 --> 02:00:51,015 A LOT OF THINGS WE CARE ABOUT IT 2305 02:00:51,015 --> 02:00:53,685 TEMPORAL PRECISION AND KNOWING 2306 02:00:53,685 --> 02:00:54,852 WHETHER YOU'RE GETTING 2307 02:00:54,852 --> 02:00:58,389 EXCITATION AND LOOK AT THE 2308 02:00:58,389 --> 02:01:03,494 RHODOPSIN'S NATURALLY OCCURRING 2309 02:01:03,494 --> 02:01:05,063 AND COMPLEMENTARY TOOLS AND SAME 2310 02:01:05,063 --> 02:01:06,497 EXPRESSION SYSTEMS COULD BE USED 2311 02:01:06,497 --> 02:01:09,067 FOR THE RHODOPSIN'S AS WELL. 2312 02:01:09,067 --> 02:01:19,377 THANK YOU AS MUCH. 2313 02:01:27,185 --> 02:01:37,629 >> I'M VERY PLEASED SO SPEAK 2314 02:01:37,996 --> 02:01:42,433 ABOUT CARDIORESPIRATORY AND 2315 02:01:42,433 --> 02:01:44,736 GASTROINTESTINAL INSIGHTS IN 2316 02:01:44,736 --> 02:01:45,503 PSYCHIATRIC DISORDERS AND I'D 2317 02:01:45,503 --> 02:01:49,340 LIKE TO THANK OUR TRAINEES FOR 2318 02:01:49,340 --> 02:01:52,310 THEIR DEDICATION TO OUR WORK AND 2319 02:01:52,310 --> 02:01:53,411 COLLABORATIONS AND INSTITUTION. 2320 02:01:53,411 --> 02:01:57,849 I WANT TO IT START WITH AN 2321 02:01:57,849 --> 02:01:59,817 UPDATED VIEW OF INTEROCEPTION 2322 02:01:59,817 --> 02:02:00,151 PUBLICATIONS. 2323 02:02:00,151 --> 02:02:05,790 YOU HAVE YOU NOBEL LAUREATES AND 2324 02:02:05,790 --> 02:02:08,192 AT THE END IN PART FOR DISCOVERY 2325 02:02:08,192 --> 02:02:11,195 OF THE RECEPTOR BUT THAT'S NOT 2326 02:02:11,195 --> 02:02:12,196 WHERE IT ENDS. 2327 02:02:12,196 --> 02:02:14,298 THE START OF INTEREST WAS 2328 02:02:14,298 --> 02:02:19,303 IGNITED IN THE EARLY PART OF THE 2329 02:02:19,303 --> 02:02:23,274 CENTURY BY BUD CRAIG WHO DIED IN 2330 02:02:23,274 --> 02:02:27,578 AT 71 AND WOULD LIKE TO TAKE A 2331 02:02:27,578 --> 02:02:29,113 MOMENT TO ACKNOWLEDGE HIS 2332 02:02:29,113 --> 02:02:30,381 CONTRIBUTIONS TO THE FIELD OF 2333 02:02:30,381 --> 02:02:31,115 NEUROSCIENCE. 2334 02:02:31,115 --> 02:02:35,119 AS A CLINICIAN I'D ALSO LIKE TO 2335 02:02:35,119 --> 02:02:39,490 REFLECT ON THIS QUOTE FROM A 2336 02:02:39,490 --> 02:02:50,034 UROLOGIST WHO REVIEWED A BOOK ON 2337 02:02:50,234 --> 02:02:52,036 INTEROCEPTION THOUGH WE'VE BEEN 2338 02:02:52,036 --> 02:02:53,905 AWARE THERE'S BEEN FEW METHODS 2339 02:02:53,905 --> 02:02:55,339 OF UNDERSTANDING THE UNDERLYING 2340 02:02:55,339 --> 02:02:57,875 PRINCIPLES IN HUMANS UNTIL THE 2341 02:02:57,875 --> 02:02:59,544 ADVENT OF FUNCTIONAL IMAGING. 2342 02:02:59,544 --> 02:03:03,514 WHILE I'D AGREE WITH HER 2343 02:03:03,514 --> 02:03:05,917 FUNCTIONAL NEUROIMAGING 2344 02:03:05,917 --> 02:03:08,352 FACILITATED MECHANISTIC 2345 02:03:08,352 --> 02:03:10,455 ASSESSMENTS IN CERTAIN PATIENTS 2346 02:03:10,455 --> 02:03:13,357 THERE'S LACK OF TOOLS FOR 2347 02:03:13,357 --> 02:03:14,058 PROBING HUMAN INTEROCEPTION. 2348 02:03:14,058 --> 02:03:16,894 THAT'S STARTING TO CHANGE. 2349 02:03:16,894 --> 02:03:19,697 AND MY TAKE HOME MESSAGE IS 2350 02:03:19,697 --> 02:03:22,934 PERIPHERAL ORGAN SIGNALS IS AN 2351 02:03:22,934 --> 02:03:27,405 OPTIMAL WAY TO UNDERSTAND HOW IT 2352 02:03:27,405 --> 02:03:28,706 CAUSES SYMPTOM PERCEPTION TO YOU 2353 02:03:28,706 --> 02:03:30,541 ARE IN A DISORDER-RELEVANT 2354 02:03:30,541 --> 02:03:30,775 FASHION. 2355 02:03:30,775 --> 02:03:37,915 OUR INTERNAL ORGANS ARE NOT 2356 02:03:37,915 --> 02:03:47,058 MERELY PHYSIOLOGIC WORKHORSES 2357 02:03:47,058 --> 02:03:48,092 AND THEY COME INTO SHARP FOCUS 2358 02:03:48,092 --> 02:03:49,927 WEN THE PHYSIOLOGY IS DISRUPTED 2359 02:03:49,927 --> 02:03:51,062 OR THREATS ARE PERCEIVED. 2360 02:03:51,062 --> 02:03:56,000 CAN SEE EXAMPLES HERE. 2361 02:03:56,000 --> 02:03:57,902 USING MECHANISMS THE BRAIN THEN 2362 02:03:57,902 --> 02:04:01,005 BUILDS PRECISE MODELS OF THE 2363 02:04:01,005 --> 02:04:05,143 BODY IN THE EXTERNAL WORLDS AND 2364 02:04:05,143 --> 02:04:09,514 ALLOW INDIVIDUAL TO TAKE 2365 02:04:09,514 --> 02:04:12,483 PREVENTIVE ACTIONS TO FOCUS ON 2366 02:04:12,483 --> 02:04:14,952 PREVENTING AVERSIVE ONES AND I 2367 02:04:14,952 --> 02:04:17,288 THINK ANIMALS DO IT TOO AND CAN 2368 02:04:17,288 --> 02:04:25,296 MODEL SIMILAR PROCESSES. 2369 02:04:25,296 --> 02:04:27,498 I'VE WORKED TO MEASURE 2370 02:04:27,498 --> 02:04:29,133 INTEROCEPTIVE PROCESSES IN 2371 02:04:29,133 --> 02:04:33,437 SYSTEMS AND LOOKING AT HUMANS 2372 02:04:33,437 --> 02:04:35,606 WITH UNDERLYING PSYCHIATRIC 2373 02:04:35,606 --> 02:04:37,375 DISORDERS AND LOOKED AT 2374 02:04:37,375 --> 02:04:39,110 SIGNALLING AND WHILE THERE'S 2375 02:04:39,110 --> 02:04:40,945 BEEN FOCUS ON THE AFFECT OF 2376 02:04:40,945 --> 02:04:42,146 CORTISOL SIGNALLING ON THE BRAIN 2377 02:04:42,146 --> 02:04:46,384 LESS WORK HAS BEEN FOCUSSED ON 2378 02:04:46,384 --> 02:04:50,621 EXAMINING THE PROCESS OF 2379 02:04:50,621 --> 02:04:54,192 GABAERGIC SIGNALS AND LOOKING AT 2380 02:04:54,192 --> 02:04:58,863 DRUGS SIMILAR TO ADRENALINE 2381 02:04:58,863 --> 02:04:59,597 WE'VE MADE PROGRESS. 2382 02:04:59,597 --> 02:05:04,735 IT GIVES US A NICE MODEL FOR 2383 02:05:04,735 --> 02:05:10,241 MANIPULATING THE PERIPHERAL 2384 02:05:10,241 --> 02:05:10,508 CIRCUITS. 2385 02:05:10,508 --> 02:05:12,510 WE'VE ESTABLISHED THE 2386 02:05:12,510 --> 02:05:13,077 REPEATABILITY ON INCREASING 2387 02:05:13,077 --> 02:05:22,453 CARDIAC ACTIVITY. 2388 02:05:22,453 --> 02:05:24,522 AND USING A CONTINUOUS RATING 2389 02:05:24,522 --> 02:05:27,325 DIAL WE CAN SEE A REAL-TIME 2390 02:05:27,325 --> 02:05:28,459 INDICATOR OF RESPIRATORY 2391 02:05:28,459 --> 02:05:28,860 SENSATION. 2392 02:05:28,860 --> 02:05:31,062 YOU MAY THINK THIS AS A PANIC 2393 02:05:31,062 --> 02:05:37,869 PATIENT COMING IN TO YOUR E.R. 2394 02:05:37,869 --> 02:05:44,242 COMPLAINING OF A DYSPNEA AND 2395 02:05:44,242 --> 02:05:46,344 SOME ELICIT STRONG SENSATIONS 2396 02:05:46,344 --> 02:05:49,213 AND OTHERS ELICIT LOWER BUT 2397 02:05:49,213 --> 02:05:49,947 DETECTABLE RESPONSES AND WE'LL 2398 02:05:49,947 --> 02:05:53,217 COME BACK TO THAT IN A BIT. 2399 02:05:53,217 --> 02:05:55,486 OVER ALL WE'RE ABLE TO DETERMINE 2400 02:05:55,486 --> 02:06:01,926 THE INTEROCEPTIVE AWARENESS AND 2401 02:06:01,926 --> 02:06:08,399 WE CAN RELIABLY INCREASE SIGNALS 2402 02:06:08,399 --> 02:06:11,002 WITH DISCREET LOCALIZATION TO 2403 02:06:11,002 --> 02:06:13,271 AREAS WHERE THE HEART STRIKES 2404 02:06:13,271 --> 02:06:23,814 AGAINST THE ANTERIOR WALL AS -- 2405 02:06:57,381 --> 02:07:00,751 ASSIYSTOLE AND WE HAVE AN 2406 02:07:00,751 --> 02:07:01,919 INDICATOR OF THE 2407 02:07:01,919 --> 02:07:03,521 CARDIORESPIRATORY SENSATIONS AND 2408 02:07:03,521 --> 02:07:05,923 THE OTHER STUDY STAFF ON THE 2409 02:07:05,923 --> 02:07:13,998 OTHER SIDE. 2410 02:07:13,998 --> 02:07:17,368 AND THE DISORDER REVEALED THE 2411 02:07:17,368 --> 02:07:19,770 RESPONSE TO THIS AND THIS WAS 2412 02:07:19,770 --> 02:07:22,640 MOST APPARENT IN 0.5 MICRO S NOT 2413 02:07:22,640 --> 02:07:27,511 THE 2 MICROGRAM DOSE AND 2414 02:07:27,511 --> 02:07:29,613 REPORTED REPORTING AT THE SAME 2415 02:07:29,613 --> 02:07:29,880 SENSATION. 2416 02:07:29,880 --> 02:07:32,350 ON THE BOTTOM IS THE HEART RATE 2417 02:07:32,350 --> 02:07:33,250 RESPONSE AND THE DIFFERENCE 2418 02:07:33,250 --> 02:07:34,785 BETWEEN THE TWO GROUPS AND THE 2419 02:07:34,785 --> 02:07:37,755 DIAL RATING AND THE INTENSITY 2420 02:07:37,755 --> 02:07:38,889 DIFFERENCES IN THE ONGOING 2421 02:07:38,889 --> 02:07:44,695 MOMENT TO MOMENT PERCEPTION. 2422 02:07:44,695 --> 02:07:50,768 THOUGH WE NOTED DOSE-DEPENDENT 2423 02:07:50,768 --> 02:07:53,237 DIFFERENCES IN THE INSULAR THERE 2424 02:07:53,237 --> 02:07:57,908 WAS A HYPOACTIVATION OF THE 2425 02:07:57,908 --> 02:08:00,778 CORTEX ASSOCIATED WITH CARDIAC 2426 02:08:00,778 --> 02:08:02,913 SENSATION AND ONLY OCCURRED AT 2427 02:08:02,913 --> 02:08:06,617 THE 0.5 MICROGRAM DOSE. 2428 02:08:06,617 --> 02:08:09,487 THIS SUGGESTS IT MAY REFLECT A 2429 02:08:09,487 --> 02:08:12,990 FAILURE TO CONSTRAIN LOW TO 2430 02:08:12,990 --> 02:08:15,259 MODERATE LEVELS OF THE 2431 02:08:15,259 --> 02:08:15,726 ASYMPATHETIC AROUSAL. 2432 02:08:15,726 --> 02:08:22,933 THIS FINDINGS COULD HAVE 2433 02:08:22,933 --> 02:08:23,834 POTENTIALLY THERAPEUTIC 2434 02:08:23,834 --> 02:08:25,336 IMPLICATIONS AND MORE NEEDS TO 2435 02:08:25,336 --> 02:08:32,076 BE STUDIED. 2436 02:08:32,076 --> 02:08:35,212 THIS IS COMPATIBLE WITH THE 2437 02:08:35,212 --> 02:08:41,152 MOUSE OPTOGENETIC STUDY BY CARL 2438 02:08:41,152 --> 02:08:43,020 IN THE INTEROCEPTIVE PROCESSING. 2439 02:08:43,020 --> 02:08:45,122 I WAS BLOWN AWAY WHEN I READ THE 2440 02:08:45,122 --> 02:08:49,160 STUDY AND IT'S A FANTASTIC 2441 02:08:49,160 --> 02:08:51,395 DEMONSTRATION OF ANIMAL AND 2442 02:08:51,395 --> 02:08:52,396 HUMAN FINDINGS AND THIS RAISES 2443 02:08:52,396 --> 02:08:55,800 SEVERAL NEW QUESTIONS. 2444 02:08:55,800 --> 02:09:00,104 FOR EXAMPLE, WHY DOES SILENCING 2445 02:09:00,104 --> 02:09:04,475 THE INSULA MITIGATE BEHAVIORS IN 2446 02:09:04,475 --> 02:09:06,077 MICE AND MAY THINK ABOUT THE 2447 02:09:06,077 --> 02:09:08,446 DIFFERENCES BETWEEN ANIMALS AND 2448 02:09:08,446 --> 02:09:11,882 HUMANS IN TERMS OF COGNITION AND 2449 02:09:11,882 --> 02:09:15,519 COGNITIVE RESTRUCTURING WORK IN 2450 02:09:15,519 --> 02:09:23,394 COGNITIVE BEHAVIORAL THERAPY. 2451 02:09:23,394 --> 02:09:27,498 FINALLY, HOW ARE OTHER NEURAL 2452 02:09:27,498 --> 02:09:29,200 INDICATORS OF CARDIAC 2453 02:09:29,200 --> 02:09:30,501 INTEROCEPTION WITH GENERALIZED 2454 02:09:30,501 --> 02:09:30,968 ANXIETY DISORDER. 2455 02:09:30,968 --> 02:09:33,904 I'D LIKE TO POINT YOU TO THE 2456 02:09:33,904 --> 02:09:37,875 POSTER OF A POSTDOC IN THE LAB 2457 02:09:37,875 --> 02:09:41,912 POSTER NUMBER 3 AND HAS A POSTER 2458 02:09:41,912 --> 02:09:52,089 TOMORROW. 2459 02:09:55,726 --> 02:09:57,928 AND STIMULATION CAUSED 2460 02:09:57,928 --> 02:10:02,533 CONNECTIVITY REDUCTIONS BETWEEN 2461 02:10:02,533 --> 02:10:05,336 CENTRAL AUTONOMIC BRAIN MOTORS 2462 02:10:05,336 --> 02:10:06,904 AND OTHER REGIONS. 2463 02:10:06,904 --> 02:10:11,075 THESE FUNCTIONAL CONNECTIVITY 2464 02:10:11,075 --> 02:10:13,310 CHANGES SUGGEST STATE-DEPENDENT 2465 02:10:13,310 --> 02:10:14,612 SIGNALLING BETWEEN CENTRAL 2466 02:10:14,612 --> 02:10:21,886 AUTONOMIC AND SENSORIMOTOR ARE 2467 02:10:21,886 --> 02:10:24,555 LINKED TO EXCITATION AND 2468 02:10:24,555 --> 02:10:27,658 VISCERAL REGULATION IN THE END. 2469 02:10:27,658 --> 02:10:29,527 I'D LIKE TO SWITCH FROM SO THESE 2470 02:10:29,527 --> 02:10:33,230 ANIMAL AND HUMAN STUDIES RAISE 2471 02:10:33,230 --> 02:10:34,932 AN IMPORTANT QUESTION REGARDING 2472 02:10:34,932 --> 02:10:36,500 INTEROCEPTION AND CORTICAL 2473 02:10:36,500 --> 02:10:36,767 FUNCTION. 2474 02:10:36,767 --> 02:10:39,503 IS THE INSULAR CORTEX TRULY THE 2475 02:10:39,503 --> 02:10:47,144 INTERFA FAFACE FOR THE BOTTOM-U 2476 02:10:47,144 --> 02:10:47,878 PROCESSES. 2477 02:10:47,878 --> 02:10:49,313 AND IT'S IMPORTANT TO NOTE 2478 02:10:49,313 --> 02:10:52,850 THERE'S NO ANATOMICAL HYPOTHESES 2479 02:10:52,850 --> 02:11:00,424 REGARDING THE POSTERIOR INSULA 2480 02:11:00,424 --> 02:11:03,327 AND REGARDING FUTURE ORIENTED 2481 02:11:03,327 --> 02:11:04,962 BODILY STATES AND THE MID 2482 02:11:04,962 --> 02:11:07,364 INSULAR CORTEX IN PROCESSING. 2483 02:11:07,364 --> 02:11:09,500 SO WE'VE BEEN INVESTIGATING IN 2484 02:11:09,500 --> 02:11:15,506 THE LAB WHERE IN THE BRAIN IE 2485 02:11:15,506 --> 02:11:16,907 INSULA THESE ACROSS FOR 2486 02:11:16,907 --> 02:11:18,576 PSYCHIATRIC DISORDERS. 2487 02:11:18,576 --> 02:11:21,278 TO LEARN MORE CHECK OUT THE FSM 2488 02:11:21,278 --> 02:11:21,979 POSTER BY A GRADUATE STUDENT IN 2489 02:11:21,979 --> 02:11:27,518 THE LAB. 2490 02:11:27,518 --> 02:11:30,387 I'D LIKE TO SWITCH TO A NEW 2491 02:11:30,387 --> 02:11:33,390 METHOD FOR PERTURBING GUT-BRAIN 2492 02:11:33,390 --> 02:11:34,391 COMMUNICATION DEVELOPED. 2493 02:11:34,391 --> 02:11:38,495 INVOLVING A MINIMALLY INVASIVE 2494 02:11:38,495 --> 02:11:42,066 DEVICE TO EVOKE MECHANO 2495 02:11:42,066 --> 02:11:42,499 SENSATION. 2496 02:11:42,499 --> 02:11:43,601 THIS IS A SUMMARY OF THE METHODS 2497 02:11:43,601 --> 02:11:45,169 FROM THE PAPER. 2498 02:11:45,169 --> 02:11:47,738 A CAPSULE YOU ACTIVATE IN A 2499 02:11:47,738 --> 02:11:49,440 BASE, YOU SWALLOW IT. 2500 02:11:49,440 --> 02:11:50,774 SHORTLY AFTER IT STARTS 2501 02:11:50,774 --> 02:11:53,310 VIBRATING ACCORDING TO A 2502 02:11:53,310 --> 02:11:55,145 PRE-DETERMINED METHOD. 2503 02:11:55,145 --> 02:11:57,381 WE ASK PARTICIPANTS TO INDICATE 2504 02:11:57,381 --> 02:12:00,718 WHETHER THEY FEEL A SENSATION IN 2505 02:12:00,718 --> 02:12:06,090 THE ABDOMEN THEY ASCRIBE TO THAT 2506 02:12:06,090 --> 02:12:06,390 STIMULATION. 2507 02:12:06,390 --> 02:12:10,761 WE ELICIT ABOVE THRESHOLD 2508 02:12:10,761 --> 02:12:13,931 CHANGES IN PERCEPTION TO DRIVE 2509 02:12:13,931 --> 02:12:19,903 THE PERCEPTUAL ACCURACY AND 2510 02:12:19,903 --> 02:12:22,906 BECAUSE IT'S A CAPSULE AND MOVE 2511 02:12:22,906 --> 02:12:31,248 IN THE GUT WE LOOKED TO IF WE 2512 02:12:31,248 --> 02:12:33,150 COULD TRACK THIS AND WE DIDN'T 2513 02:12:33,150 --> 02:12:35,686 SEE STRONG EVIDENCE OF CHANGES 2514 02:12:35,686 --> 02:12:38,822 IN ELECTROMYOGASTRIC SIGNALLING 2515 02:12:38,822 --> 02:12:44,061 AND WE'LL HEAR MORE FROM TODD. 2516 02:12:44,061 --> 02:12:50,467 AND ALSO WE SIDEFIDE THE MIDLINE 2517 02:12:50,467 --> 02:12:51,502 POSTERIOR SIGNAL NOT IN THE 2518 02:12:51,502 --> 02:12:53,904 REGION WE WORLD HAVE EXPECTED 2519 02:12:53,904 --> 02:12:56,006 BUT FOR A VARIETY OF REASONS 2520 02:12:56,006 --> 02:12:59,843 MAKES SENSE AND THESE ERP SIGNAL 2521 02:12:59,843 --> 02:13:01,912 CHANGES CORRELATED WITH 2522 02:13:01,912 --> 02:13:03,514 PERCEPTUAL ACCURACY. 2523 02:13:03,514 --> 02:13:05,149 THE VIBRATING CAPSULE RAISES 2524 02:13:05,149 --> 02:13:07,117 MANY UNANSWERED QUESTIONS. 2525 02:13:07,117 --> 02:13:10,788 WHAT ARE THE INTEROCEPTERS IN 2526 02:13:10,788 --> 02:13:12,823 THE INDUCED MECHANICAL FORCES 2527 02:13:12,823 --> 02:13:17,661 AND WHETHER IT PLAYS A ROLE AS 2528 02:13:17,661 --> 02:13:18,929 SUSPECTED FROM THIS GROUP AND 2529 02:13:18,929 --> 02:13:21,498 OTHER RELATES TO WHAT ARE THE 2530 02:13:21,498 --> 02:13:24,068 PERIPHERAL PATHWAYS PROVIDING 2531 02:13:24,068 --> 02:13:27,604 THE SENSORIES TO THE BRAIN AND 2532 02:13:27,604 --> 02:13:30,974 THERE'S EVIDENCE OF CELLULAR 2533 02:13:30,974 --> 02:13:33,544 PROCESSES AND MECHANICAL STRETCH 2534 02:13:33,544 --> 02:13:35,846 IN THE NTS. 2535 02:13:35,846 --> 02:13:39,516 ADDITIONALLY, THE POSTERIOR MID 2536 02:13:39,516 --> 02:13:43,087 LINE RAISES THE POSSIBILITY OF 2537 02:13:43,087 --> 02:13:48,492 THE DEEP MID LINE STRUCTURE SUCH 2538 02:13:48,492 --> 02:13:52,463 AS THE PRECUNIUS AND HAS 2539 02:13:52,463 --> 02:13:53,931 SENSATIONS OF SEPARATION FROM 2540 02:13:53,931 --> 02:13:57,501 THE BODY OR EVEN A SENSATION OF 2541 02:13:57,501 --> 02:14:03,407 FLOATING. 2542 02:14:03,407 --> 02:14:05,909 AND SIGNALS CAN INCREASE THE 2543 02:14:05,909 --> 02:14:08,245 SENSATION OF FLOATING AND 2544 02:14:08,245 --> 02:14:10,381 AWARENESS OF OTHER SENSATIONS IN 2545 02:14:10,381 --> 02:14:15,686 A THERAPEUTICALLY RELEVANT 2546 02:14:15,686 --> 02:14:16,587 MANNER. 2547 02:14:16,587 --> 02:14:20,057 I HAVE ONE SLIDE. 2548 02:14:20,057 --> 02:14:27,931 AND WE USE A NON-PHARMACOLOGIC 2549 02:14:27,931 --> 02:14:29,199 TOOL REDUCED ENVIRONMENTAL 2550 02:14:29,199 --> 02:14:33,170 STIMULATION THERAPY AND WHEN WE 2551 02:14:33,170 --> 02:14:36,874 ADD VISUAL, AUDITORY, SOMATO 2552 02:14:36,874 --> 02:14:38,008 SENSITIVE AND MOVEMENT RELATED 2553 02:14:38,008 --> 02:14:41,712 WE DO THIS BY HAVING PEOPLE LAY 2554 02:14:41,712 --> 02:14:43,814 IN A HIGHLY ENGINEERED 2555 02:14:43,814 --> 02:14:46,650 ENVIRONMENT A SHALLOW POOL OF 2556 02:14:46,650 --> 02:14:51,088 WATER WITH DENSE EPSON SALT 2557 02:14:51,088 --> 02:14:57,494 SOLUTION AND FLOAT EFFORTLY AND 2558 02:14:57,494 --> 02:15:00,164 ELICIT CARDIORESPIRATORY 2559 02:15:00,164 --> 02:15:03,434 SENSATIONS BUT IN A POSITIVELY 2560 02:15:03,434 --> 02:15:05,702 VALENCED MANNER VERSUS THE 2561 02:15:05,702 --> 02:15:06,970 NEGATIVE VALENCED MANNER. 2562 02:15:06,970 --> 02:15:10,808 OUR STUDIES HAVE SHOWN FLOATING 2563 02:15:10,808 --> 02:15:12,676 INDUCES A SHORT TERM EFFECT 2564 02:15:12,676 --> 02:15:18,515 LASTING UP TWO DAYS IN ANXIOUS 2565 02:15:18,515 --> 02:15:21,585 INDIVIDUALS AND SUSTAINED BODY 2566 02:15:21,585 --> 02:15:27,991 IMPROVE 2567 02:15:27,991 --> 02:15:28,325 IMPROVEMENTS. 2568 02:15:28,325 --> 02:15:32,129 WE ARE BEGINNING TO USE THIS IN 2569 02:15:32,129 --> 02:15:33,297 FLOAT-ASSISTED PSYCHO THERAPY 2570 02:15:33,297 --> 02:15:34,198 AND JUST YESTERDAY SHE GOT HER 2571 02:15:34,198 --> 02:15:37,034 NOTICE OF AWARD FOR HER K23 2572 02:15:37,034 --> 02:15:40,537 CAREER DEVELOPMENT AWARD FROM 2573 02:15:40,537 --> 02:15:48,212 NIMH SO CONGRATULATIONS. 2574 02:15:48,212 --> 02:15:55,352 IN SUMMARY, HUMAN STUDIES USING 2575 02:15:55,352 --> 02:15:56,920 INTEROCEPTIVE PERTURB BASE ARE 2576 02:15:56,920 --> 02:16:00,057 ENRICHING OUR GRASP OF THE 2577 02:16:00,057 --> 02:16:05,863 NEURAL CIRCUITS OF INTEROCEPTION 2578 02:16:05,863 --> 02:16:09,500 AND APPROACHES IN THE FUTURE. 2579 02:16:09,500 --> 02:16:09,766 THANK YOU. 2580 02:16:09,766 --> 02:16:15,038 >> THANK YOU FOR THE EXCELLENT 2581 02:16:15,038 --> 02:16:21,912 TALK. 2582 02:16:21,912 --> 02:16:22,779 >> GREAT TALK. 2583 02:16:22,779 --> 02:16:27,518 YOU LOOK AT ANY OTHER SYMPTOMS 2584 02:16:27,518 --> 02:16:32,322 OTHER THAN THE CARDIAC 2585 02:16:32,322 --> 02:16:33,924 SENSATIONS THAT COME WITH A 2586 02:16:33,924 --> 02:16:35,859 PANIC ATTACK. 2587 02:16:35,859 --> 02:16:39,563 >> WE HAVE A 2016 PAPER WHERE WE 2588 02:16:39,563 --> 02:16:44,134 USE THIS PARADIGM TO ELICIT IN 2589 02:16:44,134 --> 02:16:45,702 THE LAB PANIC ATTACKS USING THE 2590 02:16:45,702 --> 02:16:48,939 RESEARCH TO FIND CRITERIA. 2591 02:16:48,939 --> 02:16:56,747 CAN ELICIT PANIC ANXIETY IF YOU 2592 02:16:56,747 --> 02:17:00,918 ELICIT WITH A .4 MICROGRAM DOSE 2593 02:17:00,918 --> 02:17:04,588 AND CAN SEE DIZZINESS AND OTHER 2594 02:17:04,588 --> 02:17:05,889 COGNITIVE SYSTEMS. 2595 02:17:05,889 --> 02:17:07,758 THERE'S A FIGURE THAT WILL 2596 02:17:07,758 --> 02:17:09,927 DEMONSTRATE THE PANIC-RELATED 2597 02:17:09,927 --> 02:17:11,728 WITH SOMATIC SYMPTOMS IN THERE. 2598 02:17:11,728 --> 02:17:16,867 THAT PAPER WAS TRD INTERESTING 2599 02:17:16,867 --> 02:17:20,504 TO SHOW PATIENTS WITH AMYGDALA 2600 02:17:20,504 --> 02:17:22,372 LESIONS CAN REPORT FEELING 2601 02:17:22,372 --> 02:17:23,507 ANXIETY AND FEAR AND ONE PATIENT 2602 02:17:23,507 --> 02:17:33,850 EXPERIENCED A PANIC. 2603 02:17:43,360 --> 02:17:44,995 >> I'M RELATIVELY NEW TO THE 2604 02:17:44,995 --> 02:17:45,195 FIELD. 2605 02:17:45,195 --> 02:17:47,264 I THOUGHT I'D FIRST TELL YOU THE 2606 02:17:47,264 --> 02:17:51,802 STORY HOW I GOT HERE AND MY 2607 02:17:51,802 --> 02:17:57,741 ORIGINAL BACKGROUND IS IN 2608 02:17:57,741 --> 02:18:00,944 EELECTRICAL ENGINEERING AND I 2609 02:18:00,944 --> 02:18:03,447 DID A POSTDOCTORAL STUDY WITH 2610 02:18:03,447 --> 02:18:05,916 EMERY BROWN AND I BEGAN TO WORK 2611 02:18:05,916 --> 02:18:06,750 AT THE INTERSECTION OF 2612 02:18:06,750 --> 02:18:08,452 NEUROSCIENCE AND ANALYTICS AND 2613 02:18:08,452 --> 02:18:10,187 HAVE DONE SOME TECHNOLOGY 2614 02:18:10,187 --> 02:18:12,022 DEVELOPMENT AND THINGS WE'VE 2615 02:18:12,022 --> 02:18:17,427 DONE IS PARTNERING TO BUILD THIN 2616 02:18:17,427 --> 02:18:19,396 FLEXIBLE SENSORS IN THE SKIN AND 2617 02:18:19,396 --> 02:18:21,832 APPLY THEM MANY PLACES INCLUDING 2618 02:18:21,832 --> 02:18:23,967 ON THE FOREHEAD TO EXTRACT 2619 02:18:23,967 --> 02:18:29,906 THINGS LIKE EEG AND DEVELOP 2620 02:18:29,906 --> 02:18:32,509 AUTOMATED METHODS AND APPLIED 2621 02:18:32,509 --> 02:18:32,809 PROBABILITY. 2622 02:18:32,809 --> 02:18:35,779 WHAT LED ME DOUBLE THE PATH OF 2623 02:18:35,779 --> 02:18:36,113 INTEROCEPTION. 2624 02:18:36,113 --> 02:18:38,782 THIS IS ME AND MY DAD AT A 2625 02:18:38,782 --> 02:18:42,719 FAMILY REUNION AND I LOST HIM TO 2626 02:18:42,719 --> 02:18:45,155 PAN 2627 02:18:45,155 --> 02:18:50,394 PANCREATIC CANCER IN 2011 AND HE 2628 02:18:50,394 --> 02:18:55,932 LOST HIS FATHER TO GASTROCANCER 2629 02:18:55,932 --> 02:19:01,204 AND I THOUGHT THERE'S CANCER IN 2630 02:19:01,204 --> 02:19:03,473 THE FAMILY AND I THOUGHT WHAT 2631 02:19:03,473 --> 02:19:05,609 THE EKG HAS DONE FOR THE HEART 2632 02:19:05,609 --> 02:19:08,145 AND WHAT THE EEG HAS DONE FOR 2633 02:19:08,145 --> 02:19:11,615 THE BRAIN CAN WE PLACE 2634 02:19:11,615 --> 02:19:18,555 ELECTRODES ON THE ABDOMEN AND 2635 02:19:18,555 --> 02:19:20,424 EXTRACT INFORMATION FROM THE GUT 2636 02:19:20,424 --> 02:19:22,559 AND WHAT UNDER LIES THIS 2637 02:19:22,559 --> 02:19:24,394 APPROACH IS TO TAKE INTO ACCOUNT 2638 02:19:24,394 --> 02:19:29,900 THE STOMACH HAS CLEARLY HAS 2639 02:19:29,900 --> 02:19:31,268 MUSCLE CELLS TO PINCH AND 2640 02:19:31,268 --> 02:19:33,537 THERE'S ELECTRICAL PACEMAKER 2641 02:19:33,537 --> 02:19:35,939 CELLS AND THEY ALWAYS ARE 2642 02:19:35,939 --> 02:19:37,474 GENERATING OSCILLATION EVEN WHEN 2643 02:19:37,474 --> 02:19:43,880 THERE'S NO FOOD AND THE 2644 02:19:43,880 --> 02:19:47,417 MAGNITUDE OF OSCILLATION 2645 02:19:47,417 --> 02:19:49,152 INCREASES THROUGH INPUTS AND YOU 2646 02:19:49,152 --> 02:19:51,154 SEE MUSCLE TONE CHANGES. 2647 02:19:51,154 --> 02:19:53,924 AND WHAT'S INTERESTING IS THIS 2648 02:19:53,924 --> 02:20:01,798 IS ORGANIZED AN ELECTRICAL WAVE 2649 02:20:01,798 --> 02:20:06,203 MOVING FOOD DOWN THE TRACT. 2650 02:20:06,203 --> 02:20:07,104 WE TOOK ADVANTAGE OF THE 2651 02:20:07,104 --> 02:20:10,073 INFORMATION TO EXTRACT NOT JUST 2652 02:20:10,073 --> 02:20:11,742 BASIC FREQUENCY INFORMATION DONE 2653 02:20:11,742 --> 02:20:16,213 SINCE THE 1980s BUT TO EXTRACT 2654 02:20:16,213 --> 02:20:17,748 THE PATTERNING OF WHAT'S 2655 02:20:17,748 --> 02:20:18,148 OCCURRING. 2656 02:20:18,148 --> 02:20:21,017 WE HAVE HAD A SEQUENCE OF PAPERS 2657 02:20:21,017 --> 02:20:23,320 AND MONITORING THIS IN PATIENTS 2658 02:20:23,320 --> 02:20:26,690 WITH THINGS LIKE GASTROPARESIS 2659 02:20:26,690 --> 02:20:29,893 TALKED ABOUT PREVIOUSLY. 2660 02:20:29,893 --> 02:20:32,229 WE DEVELOPED FLEXIBLE 2661 02:20:32,229 --> 02:20:33,663 TECHNOLOGIES, ETCETERA TO DO 2662 02:20:33,663 --> 02:20:34,064 THAT. 2663 02:20:34,064 --> 02:20:36,800 ONE THING WE FOUND IN 2019 WAS 2664 02:20:36,800 --> 02:20:38,001 THE SPATIAL PATTERNS WHICH YOU 2665 02:20:38,001 --> 02:20:41,371 MAY THINK SHOULD GO FROM THE 2666 02:20:41,371 --> 02:20:42,939 ESOPHAGUS TO THE SMALL 2667 02:20:42,939 --> 02:20:45,909 INTESTINES DOESN'T ALWAYS OCCUR. 2668 02:20:45,909 --> 02:20:49,579 SOMETIMES THEY OPERATE IN 2669 02:20:49,579 --> 02:20:50,447 ABERRANT FASHIONS AND WITH THESE 2670 02:20:50,447 --> 02:20:52,048 WE CAN PICK UP THE INFORMATION 2671 02:20:52,048 --> 02:20:55,585 AS YOU CAN SEE IN THE ANIMATION 2672 02:20:55,585 --> 02:20:55,986 RIGHT HERE. 2673 02:20:55,986 --> 02:20:58,555 WITH THE SPATIAL INFORMATION AND 2674 02:20:58,555 --> 02:21:00,791 DOING APPROPRIATE SIGNAL 2675 02:21:00,791 --> 02:21:01,992 PROCESSING WE CAN ASSOCIATE THAT 2676 02:21:01,992 --> 02:21:04,427 WITH TO THE SYMPTOM SCORES USED 2677 02:21:04,427 --> 02:21:06,830 IN GASTROENTEROLOGY AND HOW BAD 2678 02:21:06,830 --> 02:21:10,634 IS YOUR BLOATING AND THIS AND 2679 02:21:10,634 --> 02:21:11,034 THAT. 2680 02:21:11,034 --> 02:21:13,804 THE EXTENT TO WHICH THIS SLOW 2681 02:21:13,804 --> 02:21:16,940 WAVE WAS NOT PROPAGATE FROM THE 2682 02:21:16,940 --> 02:21:17,941 ESOPHAGUS TO THE SMALL 2683 02:21:17,941 --> 02:21:20,343 INTESTINES AND THE WAY IT WAS 2684 02:21:20,343 --> 02:21:24,114 ABNORMAL CORRELATED WITH THESE 2685 02:21:24,114 --> 02:21:29,419 SYSTEMS AND GET AGGREGATE WILL 2686 02:21:29,419 --> 02:21:32,989 TO A ZERO AND PERCENTAGE OF SLOW 2687 02:21:32,989 --> 02:21:34,124 WAVES ABNORMAL. 2688 02:21:34,124 --> 02:21:44,601 WE FOUND A CORRELATION HERE. 2689 02:21:53,076 --> 02:21:57,414 THIS CORRELATES WITH THE SYSTEMS 2690 02:21:57,414 --> 02:22:00,317 AND IF WE DON'T EQUATE WITH HOW 2691 02:22:00,317 --> 02:22:01,918 SOMETHING FEELS HOW USEFUL ARE 2692 02:22:01,918 --> 02:22:07,657 THEY AND THE CONNECTION TO 2693 02:22:07,657 --> 02:22:08,692 INTEROCEPTION BECOMES 2694 02:22:08,692 --> 02:22:09,693 INTERESTING BECAUSE THE NINDS 2695 02:22:09,693 --> 02:22:11,228 PROGRAM OFFICER SPOKE ABOUT WORK 2696 02:22:11,228 --> 02:22:13,763 FROM THE UNIVERSITY OF MICHIGAN 2697 02:22:13,763 --> 02:22:15,498 WHERE THEY DID SOMETHING WHERE 2698 02:22:15,498 --> 02:22:18,034 THEY SEVERED THE VAGUS. 2699 02:22:18,034 --> 02:22:21,504 THANE PAPER AND THIS GOES BACK 2700 02:22:21,504 --> 02:22:23,006 TO HYPOTHESIS THE SLOW WAVE 2701 02:22:23,006 --> 02:22:24,341 OCCURRING IS PRIMARILY AN 2702 02:22:24,341 --> 02:22:33,550 AFFERENT TYPE OF SIGNAL. 2703 02:22:33,550 --> 02:22:34,951 TAKING THAT INTO CONSIDERATION 2704 02:22:34,951 --> 02:22:36,853 IS DUE TO AFFERENT SIGNALLING 2705 02:22:36,853 --> 02:22:39,256 AND THERE'S A SIMPLE DIAGRAM 2706 02:22:39,256 --> 02:22:41,925 WHEN YOU CONSUME A MEAL THERE'S 2707 02:22:41,925 --> 02:22:45,795 A VAGAL-VAGAL REFLEX THAT OCCURS 2708 02:22:45,795 --> 02:22:49,933 AND THE SENSATION LEADS TO 2709 02:22:49,933 --> 02:22:53,904 AFFERENT STIMULATION AND BRAIN 2710 02:22:53,904 --> 02:22:57,507 AREAS AND THE CORTEX HAS A 2711 02:22:57,507 --> 02:23:01,845 PRIMARY SENSORY COMPONENT OF THE 2712 02:23:01,845 --> 02:23:03,313 INSULA AND IT GETS INFORMATION 2713 02:23:03,313 --> 02:23:04,981 AND SENDS IT BACK DOWN STREAM 2714 02:23:04,981 --> 02:23:06,716 AND GO FROM THE BRAIN STEM BANG 2715 02:23:06,716 --> 02:23:09,920 TO THE STOMACH. 2716 02:23:09,920 --> 02:23:13,223 ONE OF THE THINGS WE GOT 2717 02:23:13,223 --> 02:23:15,525 INTERESTED IN IS IN SOME 2718 02:23:15,525 --> 02:23:16,960 PATIENTS SOME SYMPTOM SEVERITY 2719 02:23:16,960 --> 02:23:18,628 EXCEEDED WHAT WAS PREDICTED FROM 2720 02:23:18,628 --> 02:23:21,064 THE GASTRIC SLOW WAVES AND 2721 02:23:21,064 --> 02:23:23,900 THAT'S NOT SURPRISING IF YOU 2722 02:23:23,900 --> 02:23:25,735 HANG AROUND GASTROENTEROLOGISTS 2723 02:23:25,735 --> 02:23:28,571 LONG ENOUGH AND IF YOU LOOK AT 2724 02:23:28,571 --> 02:23:34,844 PATIENTS WITH GASTROPARESIS OR 2725 02:23:34,844 --> 02:23:37,914 DISPEPSIA AND THERE'S INTEREST 2726 02:23:37,914 --> 02:23:40,617 IN IDENTIFYING THE TYPES IS THIS 2727 02:23:40,617 --> 02:23:50,860 DUE TO X OR Y. 2728 02:24:01,638 --> 02:24:02,872 AND MY COLLEAGUE HAD DONE 2729 02:24:02,872 --> 02:24:03,873 INTERVENTIONS AND THESE 2730 02:24:03,873 --> 02:24:05,842 INTERVENTIONS DID NOT TARGET THE 2731 02:24:05,842 --> 02:24:06,710 SLOW WAVE. 2732 02:24:06,710 --> 02:24:09,512 THINGS LIKE GIVING SOMEONE BOTOX 2733 02:24:09,512 --> 02:24:10,780 ON THE BOTTOM OF THE STOMACH 2734 02:24:10,780 --> 02:24:12,716 WHICH CAN HELP WITH THE OPENING 2735 02:24:12,716 --> 02:24:16,653 AND CLOSING TO THE SMALL 2736 02:24:16,653 --> 02:24:18,655 INTESTINES OR PROVIDE 2737 02:24:18,655 --> 02:24:28,865 PROKINETIC. 2738 02:24:32,068 --> 02:24:33,903 AND THE SYSTEMS UPON TREATMENT 2739 02:24:33,903 --> 02:24:35,872 DIDN'T TARGET THE SLOW WAVE AND 2740 02:24:35,872 --> 02:24:37,574 GOT TO THE REGRESSION LINE. 2741 02:24:37,574 --> 02:24:40,410 ALL THE PATIENTS WHO WERE ON THE 2742 02:24:40,410 --> 02:24:41,111 REGRESSION LINE THEIR SYSTEMS 2743 02:24:41,111 --> 02:24:42,979 WERE UNCHANGED. 2744 02:24:42,979 --> 02:24:44,948 THIS IS FURTHER CONFIRMATION 2745 02:24:44,948 --> 02:24:46,116 WHAT THIS REGRESSION LINE 2746 02:24:46,116 --> 02:24:47,650 ASSOCIATED PREDICTED FROM THE 2747 02:24:47,650 --> 02:24:50,253 SLOW WAVE IS TELLING US ABOUT 2748 02:24:50,253 --> 02:24:53,890 THE SEVERITY OF SYSTEMS 2749 02:24:53,890 --> 02:24:55,725 ASSOCIATED WITH THE SLOW WAVE 2750 02:24:55,725 --> 02:24:58,461 AND CAN SEE IF THE SYMPTOM 2751 02:24:58,461 --> 02:25:01,164 SEVERITY EXCEEDS THAT SUGGESTS 2752 02:25:01,164 --> 02:25:02,165 OTHER ALTERNATIVES CAN BE 2753 02:25:02,165 --> 02:25:02,432 USEFUL. 2754 02:25:02,432 --> 02:25:04,567 THIS WAS IMPORTANT IN TAKING A 2755 02:25:04,567 --> 02:25:05,869 LOOK AT THE SLOW WAVE 2756 02:25:05,869 --> 02:25:08,271 INFORMATION AND ASSOCIATION WITH 2757 02:25:08,271 --> 02:25:08,605 INTEROCEPTION. 2758 02:25:08,605 --> 02:25:10,707 AND ONE THING WE ALSO WANTED TO 2759 02:25:10,707 --> 02:25:12,942 DO WAS GO BEYOND YOU WAITING SIX 2760 02:25:12,942 --> 02:25:14,377 MONTHS TO SEE THE G.I. 2761 02:25:14,377 --> 02:25:14,677 SPECIALIST. 2762 02:25:14,677 --> 02:25:16,646 WHEN THEY ASK THE QUESTIONNAIRE 2763 02:25:16,646 --> 02:25:18,681 IT'S OVER THE LAST SIX MONTHS OR 2764 02:25:18,681 --> 02:25:20,483 YEAR WHAT OCCURRED AND GET 2765 02:25:20,483 --> 02:25:21,217 MEASURED ONCE. 2766 02:25:21,217 --> 02:25:24,087 THIS ASSOCIATION IS NOT EXACTLY 2767 02:25:24,087 --> 02:25:25,822 CORRECT TEMPORALLY. 2768 02:25:25,822 --> 02:25:31,895 WHAT IF WE CAN PROVIDE AN 2769 02:25:31,895 --> 02:25:33,029 AMBULATORY DEVICE AND TRACK YOUR 2770 02:25:33,029 --> 02:25:35,498 SYMPTOMS AND WE DEVELOPED A 2771 02:25:35,498 --> 02:25:36,466 TECHNIQUE AND ONE THING WE CAN 2772 02:25:36,466 --> 02:25:39,135 DO IS YOU CONSUME A MEAL AS YOU 2773 02:25:39,135 --> 02:25:41,905 SEE IN THE PLOT AND WE CAN SEE 2774 02:25:41,905 --> 02:25:44,707 THE AMPLITUDE OF THE 2775 02:25:44,707 --> 02:25:46,576 OSCILLATIONS WHEN THE STOMACH 2776 02:25:46,576 --> 02:25:51,514 RESPONSES AND FEW DESCENDED TO 2777 02:25:51,514 --> 02:25:55,218 THE STOMACH AND GIVES RISE TO 2778 02:25:55,218 --> 02:25:59,022 THE OSCILLATION AS MANIFESTED IN 2779 02:25:59,022 --> 02:26:00,356 THE SPECTRAL POWER INCREASING 2780 02:26:00,356 --> 02:26:05,862 BECAUSE OF OUR ARRAY IT CAN 2781 02:26:05,862 --> 02:26:08,731 TRACK TEMPORAL THE SPATIAL 2782 02:26:08,731 --> 02:26:10,600 PATTERNS THAT OCCUR AND WHAT ARE 2783 02:26:10,600 --> 02:26:14,404 THE SYMPTOMS THAT OCCUR AND WHEN 2784 02:26:14,404 --> 02:26:23,947 DO WE SEE ABNORMALITIES. 2785 02:26:23,947 --> 02:26:27,217 WHEN WE THINK WITH THE 2786 02:26:27,217 --> 02:26:29,385 CONNECTION WITH THE BRAIN STEM 2787 02:26:29,385 --> 02:26:35,458 IT'S MEDIATED BY THE VAGUS NERVE 2788 02:26:35,458 --> 02:26:39,329 AND NOT OPERATING CORRECTLY. 2789 02:26:39,329 --> 02:26:42,532 I TALKED TO SOME CARDIOLOGY 2790 02:26:42,532 --> 02:26:44,868 BUDDIES AND ASKED ARE THERE 2791 02:26:44,868 --> 02:26:47,670 INTERESTING WAYS WE CAN THINK OF 2792 02:26:47,670 --> 02:26:51,074 TRACKING THE HEART FOR THE 2793 02:26:51,074 --> 02:26:53,543 SYSTEM AND THEY SAID BE CAREFUL 2794 02:26:53,543 --> 02:26:55,945 BECAUSE THE HEART IS RESPONDING 2795 02:26:55,945 --> 02:26:58,114 TO COMMANDS FROM THE BODY ALL 2796 02:26:58,114 --> 02:27:00,350 THE TIME BUT WHEN YOU'RE ASLEEP 2797 02:27:00,350 --> 02:27:01,050 IT'S INTERESTING BECAUSE THERE'S 2798 02:27:01,050 --> 02:27:06,623 NOT MANY DEMAND AND THE 2799 02:27:06,623 --> 02:27:07,590 PARASYMPATHETIC NERVOUS SYSTEM 2800 02:27:07,590 --> 02:27:10,059 IS MORE ACTIVE WHEN YOU SLEEP 2801 02:27:10,059 --> 02:27:13,429 AND CAN GET THE HEART BEATS AND 2802 02:27:13,429 --> 02:27:17,267 DEVELOP LOOKING AT THE HEART 2803 02:27:17,267 --> 02:27:20,103 RATE AND CONTRIBUTION FROM 2804 02:27:20,103 --> 02:27:28,378 SYMPATHETIC AND PARASYMPATHETIC 2805 02:27:28,378 --> 02:27:29,913 NERVOUS SYSTEM AND WHEN THE 2806 02:27:29,913 --> 02:27:33,583 PATIENT WENT TO SLEEP THIS 2807 02:27:33,583 --> 02:27:37,453 THERE'S MORE PARASYMPATHETIC 2808 02:27:37,453 --> 02:27:40,023 INTERVENTION WHEN YOU SLEEP. 2809 02:27:40,023 --> 02:27:44,694 THE BOTTOM PLOT IS WITH SOMEONE 2810 02:27:44,694 --> 02:27:45,728 WITH APARESIS. 2811 02:27:45,728 --> 02:27:48,398 THERE'S NO CHANGE IN THE RATIO 2812 02:27:48,398 --> 02:27:53,403 IN SLEEP VERSUS WAKE SUGGESTING 2813 02:27:53,403 --> 02:27:54,571 THE PARASYMPATHETIC IS MORE 2814 02:27:54,571 --> 02:27:57,507 ACTIVE DURING SLEEP. 2815 02:27:57,507 --> 02:27:59,209 MOREOVER THE RATIO IS NOT AS 2816 02:27:59,209 --> 02:27:59,409 LARGE. 2817 02:27:59,409 --> 02:28:02,312 IT'S MUCH ATTENUATED ACROSS THE 2818 02:28:02,312 --> 02:28:04,180 BOARD. 2819 02:28:04,180 --> 02:28:06,749 AND THE PATIENT WITH DIABETIC 2820 02:28:06,749 --> 02:28:07,083 GASTROPARESIS. 2821 02:28:07,083 --> 02:28:08,751 WE TAKE THE INFORMATION ABOUT 2822 02:28:08,751 --> 02:28:10,353 THE MEAL RESPONSE I ALLUDED TO 2823 02:28:10,353 --> 02:28:13,156 AND LOOKING AT THE INTENSITY AS 2824 02:28:13,156 --> 02:28:13,923 WELL AS THE REGULATION AND HOW 2825 02:28:13,923 --> 02:28:15,325 MUCH DID IT CHANGE BEFORE AND 2826 02:28:15,325 --> 02:28:17,160 AFTER CONSUMPTION OF A MEAL AND 2827 02:28:17,160 --> 02:28:18,461 LOOKING AT THE SAME INFORMATION 2828 02:28:18,461 --> 02:28:21,864 WITH THE HEART ASSOCIATED WITH 2829 02:28:21,864 --> 02:28:24,133 THE PARASYMPATHETIC NERVOUS 2830 02:28:24,133 --> 02:28:26,369 SYSTEM AND WE SAW SEPARATION 2831 02:28:26,369 --> 02:28:28,271 AGAIN GROUPS AND COULD BUILD 2832 02:28:28,271 --> 02:28:30,406 CLASSIFIERS THAT COULD SEPARATE 2833 02:28:30,406 --> 02:28:35,478 HEALTHY FROM CONTROLS AND 2834 02:28:35,478 --> 02:28:36,346 DIABETIC GASTROPARESIS VERSUS 2835 02:28:36,346 --> 02:28:41,050 NON WITH HIGH ACCURACY. 2836 02:28:41,050 --> 02:28:49,425 I GOT INTERESTED IN WE MOVED TO 2837 02:28:49,425 --> 02:28:51,628 PROBING OF INTEROCEPTION WAS A 2838 02:28:51,628 --> 02:28:53,930 BIT INDIRECT AND WERE NOT 2839 02:28:53,930 --> 02:28:54,564 AMERICA INFORMATION FROM THE 2840 02:28:54,564 --> 02:28:55,531 BRAIN SIMULTANEOUSLY. 2841 02:28:55,531 --> 02:28:57,133 ONE THING I GOT INTERESTED IN 2842 02:28:57,133 --> 02:28:59,202 DOING WAS EXPLORING IN HUMANS 2843 02:28:59,202 --> 02:29:02,705 CAN WE DO THIS AND WE GOT LUCKY 2844 02:29:02,705 --> 02:29:09,012 BECAUSE AS A RESEARCHER AND I'VE 2845 02:29:09,012 --> 02:29:10,947 BEEN SINGING HER PRAISES SINCE 2846 02:29:10,947 --> 02:29:13,616 THE 2017 PAPER AND PUBLISHED A 2847 02:29:13,616 --> 02:29:16,919 PAPER DOING MEG FOR THE BRAIN 2848 02:29:16,919 --> 02:29:21,424 AND THE ELECTROGASTROGRAM AND 2849 02:29:21,424 --> 02:29:25,862 SAW AT REST TWO THINGS COUPLED 2850 02:29:25,862 --> 02:29:27,964 AND PHASED AMPLITUDE COUPLING 2851 02:29:27,964 --> 02:29:31,801 AND SLOWS THE AMPLITUDE OF THE 2852 02:29:31,801 --> 02:29:32,001 MEGs. 2853 02:29:32,001 --> 02:29:34,637 THE BAD NEWS IS A LOT OF US KNOW 2854 02:29:34,637 --> 02:29:36,639 YOU CAN'T DO MEG EVERYWHERE. 2855 02:29:36,639 --> 02:29:39,475 THESE ARE THE STATES WHERE 2856 02:29:39,475 --> 02:29:41,244 THERE'S A CLINICALLY AVAILABLE 2857 02:29:41,244 --> 02:29:42,645 MEG LOCATION AND IN MANY STATES 2858 02:29:42,645 --> 02:29:45,048 THERE'S ZERO WE DON'T HAVE ONE 2859 02:29:45,048 --> 02:29:46,282 AT STANFORD. 2860 02:29:46,282 --> 02:29:50,153 THERE'S ONE AT UC SAN DIEGO AND 2861 02:29:50,153 --> 02:29:53,556 UCSF AND NOT ONE HERE AND WE 2862 02:29:53,556 --> 02:29:54,824 MEASURED ELECTROMAGNETIC 2863 02:29:54,824 --> 02:29:57,126 ACTIVITY AND CAN WE DO ANALOGOUS 2864 02:29:57,126 --> 02:29:57,794 STUDIES. 2865 02:29:57,794 --> 02:29:58,995 WE DID SIMULTANEOUSLY STUDIES 2866 02:29:58,995 --> 02:30:01,364 TRYING TO MIRROR WHAT SHE DID IN 2867 02:30:01,364 --> 02:30:06,636 HER 2017 PAPER REPLACING THE MEG 2868 02:30:06,636 --> 02:30:13,209 WITH ENG AND WERE ABLE TO LOOK 2869 02:30:13,209 --> 02:30:16,312 AT THE COUPLING AND WE EXPLORED 2870 02:30:16,312 --> 02:30:19,582 NOT DURING THE RESTING STATE BUT 2871 02:30:19,582 --> 02:30:21,451 ENGAGING IN COGNITIVE TASKS AND 2872 02:30:21,451 --> 02:30:23,119 THERE'S GREATER COUPLING IN THE 2873 02:30:23,119 --> 02:30:25,922 RESTING STATE TO WORKING MEMORY 2874 02:30:25,922 --> 02:30:27,390 AND MIGHT RELATE TO WHAT WAS 2875 02:30:27,390 --> 02:30:29,926 TALKED ABOUT WHEN WHERE YOU PUT 2876 02:30:29,926 --> 02:30:32,528 SOMEONE IN THE TANKS WHERE 2877 02:30:32,528 --> 02:30:37,200 THERE'S NO INPUT AND THIS COULD 2878 02:30:37,200 --> 02:30:38,534 MAGNIFY THE STRENGTH OF THE 2879 02:30:38,534 --> 02:30:40,370 INTEROCEPTION AND IT WAS 2880 02:30:40,370 --> 02:30:43,639 MODULATED BY SATIATION AND THE 2881 02:30:43,639 --> 02:30:45,208 LEFT FRONTAL REGION AND WE TRIED 2882 02:30:45,208 --> 02:30:48,044 TO MIRROR THIS MOTION OF THE 2883 02:30:48,044 --> 02:30:49,145 GASTRIC NETWORK FOUND WITH THE 2884 02:30:49,145 --> 02:30:53,282 MEG WORK AND DOING THAT IN AN 2885 02:30:53,282 --> 02:30:55,852 ANALOGOUS EEG ELECTRODES AND THE 2886 02:30:55,852 --> 02:30:59,522 STRENGTHS OF THE COUPLING 2887 02:30:59,522 --> 02:31:00,423 CORRELATED WITH THE WORKING 2888 02:31:00,423 --> 02:31:01,257 MEMORY TASK. 2889 02:31:01,257 --> 02:31:03,126 THIS IS OUR ATTEMPT TO MIRROR 2890 02:31:03,126 --> 02:31:05,928 WHAT'S BEEN DONE BUT IN A MORE 2891 02:31:05,928 --> 02:31:09,499 SCALABLE FASHION LIKE WITH EEG 2892 02:31:09,499 --> 02:31:12,769 INSTEAD. 2893 02:31:12,769 --> 02:31:15,805 IF THESE TWO ORGANS ARE 2894 02:31:15,805 --> 02:31:16,939 ELECTRICALLY CONNECTED COULD WE 2895 02:31:16,939 --> 02:31:19,275 TREAT THE BRAIN BY STIMULATING 2896 02:31:19,275 --> 02:31:25,581 THE OTHER ORGAN CONNECTED NAMELY 2897 02:31:25,581 --> 02:31:33,823 THE STOMACH. 2898 02:31:33,823 --> 02:31:38,261 WE PARTNERED WITH CARDIOLOGY 2899 02:31:38,261 --> 02:31:43,099 FOLKS AT UCLA AND TRIED TO 2900 02:31:43,099 --> 02:31:45,101 EXPLORE IF WE CAN CHANGE 2901 02:31:45,101 --> 02:31:49,172 PARAMETERS AND IT'S WIRELESS AND 2902 02:31:49,172 --> 02:31:55,077 SO THERE'S A THIN USING 2903 02:31:55,077 --> 02:31:56,846 INDUCTIVE COUPLING AND CAN PLACE 2904 02:31:56,846 --> 02:32:01,284 IT IN A LARGE VEIN AND COUPLE IT 2905 02:32:01,284 --> 02:32:03,653 AND WE TOOK THIS APPROACH AND IN 2906 02:32:03,653 --> 02:32:07,557 A PIG MODEL WE IMPLANTED THE 2907 02:32:07,557 --> 02:32:09,926 PACING DEVICE AND ALSO PLACED 2908 02:32:09,926 --> 02:32:12,495 ELECTRODES ON THE SIDE OF THE 2909 02:32:12,495 --> 02:32:14,764 STOMACH WHERE THE SLOW WAVE WAS 2910 02:32:14,764 --> 02:32:16,766 CREATE AND MEASURE THE SPATIAL 2911 02:32:16,766 --> 02:32:17,633 PATTERNS OF THE SLOW WAVE AND 2912 02:32:17,633 --> 02:32:22,205 PLACE ELECTRODES ON THE 2913 02:32:22,205 --> 02:32:24,740 ABDOMINAL SURFACE AND WHEN WE 2914 02:32:24,740 --> 02:32:27,710 TURN THE PACING DEVICE ON WE CAN 2915 02:32:27,710 --> 02:32:30,413 EN TRAIN THE SLOW WAVE WELL AND 2916 02:32:30,413 --> 02:32:31,214 HAVE THE GROUND TRUTH BECAUSE WE 2917 02:32:31,214 --> 02:32:33,449 HAVE THE ELECTRODE ON THE 2918 02:32:33,449 --> 02:32:36,252 STOMACH AND WE SHOW UP TO AN 2919 02:32:36,252 --> 02:32:37,253 ORIENTATION CHANGE. 2920 02:32:37,253 --> 02:32:39,522 WE BASICALLY GET CONSISTENT 2921 02:32:39,522 --> 02:32:40,656 INFORMATION ABOUT THE SLOW WAVE 2922 02:32:40,656 --> 02:32:45,495 DIRECTION FROM THE ELECTRODES ON 2923 02:32:45,495 --> 02:32:55,204 THE AND ABDOMEN AND DEVELOP 2924 02:32:55,204 --> 02:32:56,606 CONTROLS. 2925 02:32:56,606 --> 02:33:02,445 CAN WE TAKE AN AB NORMAL SLOW 2926 02:33:02,445 --> 02:33:05,548 WAVE GIVING RISE TO THE SYSTEMS 2927 02:33:05,548 --> 02:33:07,283 AND MAKE CONSISTENT WAVE FROM 2928 02:33:07,283 --> 02:33:11,087 THE ESOPHAGUS TO THE STOMACH? 2929 02:33:11,087 --> 02:33:12,788 THINKING IN SHORT WHAT UNDER 2930 02:33:12,788 --> 02:33:15,124 LIES HOW WE THINK ABOUT OUR 2931 02:33:15,124 --> 02:33:16,826 RESEARCH RATHER THAN PLAYING IN 2932 02:33:16,826 --> 02:33:20,229 RED OCEAN AREA WHERE THERE'S 2933 02:33:20,229 --> 02:33:26,736 EXISTING CUT-THROAT AREAS LOOK 2934 02:33:26,736 --> 02:33:30,640 AT BLUE OCEAN AREAS AND HAVE 2935 02:33:30,640 --> 02:33:31,641 PLACE FOR GROWTH AND WITH THAT I 2936 02:33:31,641 --> 02:33:41,884 YIELD MY TALK. 2937 02:33:45,021 --> 02:33:45,821 >> ANY QUESTIONS? 2938 02:33:45,821 --> 02:33:46,222 THANK YOU. 2939 02:33:46,222 --> 02:33:51,794 >> THANK YOU FOR THE EXCITING 2940 02:33:51,794 --> 02:33:54,997 TALK. 2941 02:33:54,997 --> 02:33:57,333 THE 24-HOWEVER MONITORING WAS 2942 02:33:57,333 --> 02:33:58,067 PARTICULARLY EXCITING AND 2943 02:33:58,067 --> 02:33:59,735 WONDERING WHETHER YOU ANALYZED 2944 02:33:59,735 --> 02:34:01,304 YOUR DATA OR TOOK DATA ABOUT 2945 02:34:01,304 --> 02:34:03,105 WHAT THE PATIENTS WERE EATING 2946 02:34:03,105 --> 02:34:04,840 AND WHAT THE NUTRITIONAL CONCEPT 2947 02:34:04,840 --> 02:34:06,542 WAS AND WHETHER IT SHOWED 2948 02:34:06,542 --> 02:34:11,781 ANYTHING IN TERMS OF AFFECTING 2949 02:34:11,781 --> 02:34:22,091 ANY CHANGE IN -- 2950 02:35:02,365 --> 02:35:08,304 >> I WANT TO START BY THINKING 2951 02:35:08,304 --> 02:35:18,714 THE ORGANIZERS TODD AND 2952 02:35:23,753 --> 02:35:28,057 >> WE HAVE A PATHWAY DISCOVERED 2953 02:35:28,057 --> 02:35:32,028 IN 2018 DISCOVERED BY A GROUP 2954 02:35:32,028 --> 02:35:33,329 AND THEY'RE COLLEAGUES AND IT'S 2955 02:35:33,329 --> 02:35:37,333 A PATHWAY THAT CONNECTS THE 2956 02:35:37,333 --> 02:35:39,502 NUTRIENT SENSING AND UPPER 2957 02:35:39,502 --> 02:35:43,005 INTESTINE WITH DOPAMINE CIRCUITS 2958 02:35:43,005 --> 02:35:53,249 IN THE BRAIN. 2959 02:36:05,394 --> 02:36:10,733 AND THEY HAD PROJECTIONS THROUGH 2960 02:36:10,733 --> 02:36:19,542 THE VAGUS SERVE TO THE MID BRAIN 2961 02:36:19,542 --> 02:36:22,211 DORSAL STRIATUM AND INSPECT THE 2962 02:36:22,211 --> 02:36:24,513 CELLS THAT RECEIVE THE 2963 02:36:24,513 --> 02:36:29,785 INFORMATION FROM THE UPPER 2964 02:36:29,785 --> 02:36:32,621 INTESTINE WITH CHANNELRHODOPSIN 2965 02:36:32,621 --> 02:36:35,624 AND ALLOWS THE ANIMALS TO NOSE 2966 02:36:35,624 --> 02:36:37,760 POKE TO RECEIVE STIMULATION THAT 2967 02:36:37,760 --> 02:36:39,762 BASICALLY SIMULATES THIS SIGNAL 2968 02:36:39,762 --> 02:36:41,464 FROM THE UPPER INTESTINE. 2969 02:36:41,464 --> 02:36:44,700 YOU CAN SEE THE ANIMALS LEARN 2970 02:36:44,700 --> 02:36:48,504 OVER DAYS TO SELF-STIMULATE 2971 02:36:48,504 --> 02:36:50,806 INCLUDING IN TER EXTINCTION AND 2972 02:36:50,806 --> 02:36:54,210 WHEN THEY LOOKED AT DOPAMINE 2973 02:36:54,210 --> 02:36:55,544 EFFLUX IN THE DORSAL STRIATUM 2974 02:36:55,544 --> 02:37:00,049 YOU CAN SEE IN THE BLUE CIRCLES 2975 02:37:00,049 --> 02:37:02,051 THIS IS A RISE IN EXTRA CELLULAR 2976 02:37:02,051 --> 02:37:05,921 DOPAMINE WHEN THEY WERE 2977 02:37:05,921 --> 02:37:06,789 SIMULATING THOSE CELLS IN THE 2978 02:37:06,789 --> 02:37:09,925 NOTICE RECEIVE FROM THE UPPER 2979 02:37:09,925 --> 02:37:11,494 INTESTINE AND IN GREEN AN 2980 02:37:11,494 --> 02:37:16,298 ADJACENT GROUP OF CELLS AND THIS 2981 02:37:16,298 --> 02:37:19,001 IS GUT INDUCED AWARD. 2982 02:37:19,001 --> 02:37:20,569 UNDER PHYSIOLOGICAL CONDITIONS 2983 02:37:20,569 --> 02:37:24,840 THE PATHWAY IS NOT SENSITIVE TO 2984 02:37:24,840 --> 02:37:28,511 THERE'S ER -- TO LASERS BUT 2985 02:37:28,511 --> 02:37:28,778 LIPIDS. 2986 02:37:28,778 --> 02:37:39,221 THIS SHOWS MICRODIALYSIS. 2987 02:37:59,141 --> 02:38:00,342 AND WHAT WAS INTERESTING FOR ME 2988 02:38:00,342 --> 02:38:02,778 IS THEY SAW THIS IN ANIMALS FED 2989 02:38:02,778 --> 02:38:09,518 A LOW FAST DIET AND DIET ALONE 2990 02:38:09,518 --> 02:38:11,754 LENDS TO THIS PATHWAY AND HERE'S 2991 02:38:11,754 --> 02:38:13,589 WHAT HAPPENS WHEN YOU INFUSED 2992 02:38:13,589 --> 02:38:15,624 ANIMALS IN HIGH FAT DIET FOR 16 2993 02:38:15,624 --> 02:38:23,265 WEEKS AND DID NOT GAIN ANY WAY. 2994 02:38:23,265 --> 02:38:25,668 IT WAS ACCOMPANIED BY BEHAVIORAL 2995 02:38:25,668 --> 02:38:28,804 CHANGE ON THE Y AXIS THE ANIMALS 2996 02:38:28,804 --> 02:38:32,074 ARE LOOKING TO RECEIVE INFUSION 2997 02:38:32,074 --> 02:38:35,644 OF A LOW FAT EMULSION AND IN THE 2998 02:38:35,644 --> 02:38:39,048 DARK GREEN CIRCLES THOSE ARE THE 2999 02:38:39,048 --> 02:38:43,752 ANIMALS IN THE LOW FAT DIET AND 3000 02:38:43,752 --> 02:38:45,387 INDIFFERENT TO THE LOW FAT 3001 02:38:45,387 --> 02:38:47,156 NUTRIENT IN THE GUT. 3002 02:38:47,156 --> 02:38:48,457 REMARKABLY WHAT THEY ARE ALSO 3003 02:38:48,457 --> 02:38:59,001 SHOWED IS IF YOU CAN INFUSE OEA 3004 02:39:00,302 --> 02:39:01,637 INTO THE RATS THAT HAVE UNDER 3005 02:39:01,637 --> 02:39:04,406 GONE THE HIGH FAT DIET AND 3006 02:39:04,406 --> 02:39:06,642 REVERSE THE EFFECTS. 3007 02:39:06,642 --> 02:39:08,510 HERE YOU SEE AGAIN EXTRA 3008 02:39:08,510 --> 02:39:11,647 CELLULAR DOPAMINE AND OEA 3009 02:39:11,647 --> 02:39:13,916 INFUSION AND FOLLOWING 3010 02:39:13,916 --> 02:39:19,955 INTERLIPID THE TOP LINE IS THE 3011 02:39:19,955 --> 02:39:30,099 OVA AND. 3012 02:39:37,573 --> 02:39:41,343 AND YOU SEE THEM LICKING THE 3013 02:39:41,343 --> 02:39:43,746 EMULSION AND THEY INCREASE THEIR 3014 02:39:43,746 --> 02:39:45,781 RESPONDING FOR LOW FAT SO THE 3015 02:39:45,781 --> 02:39:47,917 ACUTE OEA ADMINISTRATION IS 3016 02:39:47,917 --> 02:39:50,152 CHANGING DOPAMINE AND CHANGING 3017 02:39:50,152 --> 02:39:50,586 PERCEPTION. 3018 02:39:50,586 --> 02:39:51,720 I THOUGHT SUPER COOL. 3019 02:39:51,720 --> 02:39:53,923 WE'VE BEEN DOING STUDIES IN 3020 02:39:53,923 --> 02:39:58,560 HUMANS TO SEE IF THIS TRANSLATES 3021 02:39:58,560 --> 02:40:03,098 AND THE FIRST STUDY IS A 3022 02:40:03,098 --> 02:40:04,934 COLLABORATION WITH A GROUP AT 3023 02:40:04,934 --> 02:40:07,336 THE INSTITUTE FOR METABOLISM 3024 02:40:07,336 --> 02:40:08,337 RESEARCH. 3025 02:40:08,337 --> 02:40:11,774 THEY HAD DEVELOPED THIS TEMPORAL 3026 02:40:11,774 --> 02:40:14,810 CLUSTERING TECHNIQUE USING PET 3027 02:40:14,810 --> 02:40:16,245 DATA AND LOOKING AT NOT WHERE IN 3028 02:40:16,245 --> 02:40:17,913 THE BRAIN YOU WERE SEEING 3029 02:40:17,913 --> 02:40:20,316 CHANGES BUT WHEN. 3030 02:40:20,316 --> 02:40:22,584 AND WE USED THIS TECHNIQUE IN A 3031 02:40:22,584 --> 02:40:25,387 GROUP OF INDIVIDUALS IN THE PET 3032 02:40:25,387 --> 02:40:28,123 SCANNER BEING SCANNED OVER 60 3033 02:40:28,123 --> 02:40:28,424 MINUTES. 3034 02:40:28,424 --> 02:40:32,394 THE RADIO LIGAND IS INJECTED AT 3035 02:40:32,394 --> 02:40:34,129 ZERO MINUTES AND PEOPLE ARE ALL 3036 02:40:34,129 --> 02:40:36,699 HUNGRY AND FROM THE 20 TO 30 3037 02:40:36,699 --> 02:40:39,535 MINUTES WE START INFUSING THEM 3038 02:40:39,535 --> 02:40:43,973 IN PREDICTED MILK SHAKE TO GET 3039 02:40:43,973 --> 02:40:48,177 THE SIGNAL AND YOU CAN SEE IN 3040 02:40:48,177 --> 02:40:49,178 FACT THERE ARE TWO SEPARATE TIME 3041 02:40:49,178 --> 02:40:51,981 POINTS OF CHANGES IN BINDING 3042 02:40:51,981 --> 02:40:52,247 POTENTIAL. 3043 02:40:52,247 --> 02:40:54,917 ONE CORRESPONDING TO WHEN THE 3044 02:40:54,917 --> 02:41:00,956 HUMAN IS CONSUMING THE MILK 3045 02:41:00,956 --> 02:41:11,467 SHAKE TO THE ORAL AND WITH TO 3046 02:41:19,041 --> 02:41:23,178 THE SAME GROUP IS MARK ON THE 3047 02:41:23,178 --> 02:41:24,747 RIGHT AND HIS POSTDOC AND MY 3048 02:41:24,747 --> 02:41:28,884 POSTDOC AT THE TIME AND THIS IS 3049 02:41:28,884 --> 02:41:31,620 ANOTHER STUDY AND WE RECRUITED 3050 02:41:31,620 --> 02:41:32,821 50 PEOPLE HEALTHY WEIGHT AND 3051 02:41:32,821 --> 02:41:35,290 CAME IN FOR A PRE TEST AND WE 3052 02:41:35,290 --> 02:41:37,226 DID STUDIES AND PREFERENCE TESTS 3053 02:41:37,226 --> 02:41:41,530 AND THE NEUROIMAGING STUDIES WAS 3054 02:41:41,530 --> 02:41:43,098 LOOKING AT BRAIN RESPONSE TO 3055 02:41:43,098 --> 02:41:46,335 CUES PREDICTING A MILK SHAKE AND 3056 02:41:46,335 --> 02:41:49,204 RESPONSE AND DID A TASK THAT HAS 3057 02:41:49,204 --> 02:41:52,207 NOTHING TO DO WITH FEEDING AND A 3058 02:41:52,207 --> 02:41:53,308 PROBABILISTIC LEARNING TASK 3059 02:41:53,308 --> 02:41:57,913 WHERE PEOPLE HAVE TO LEARN TO 3060 02:41:57,913 --> 02:41:59,314 ASSOCIATE TONES WITH THE SIGHT 3061 02:41:59,314 --> 02:42:01,450 OF A FACE OR PLACE AND THIS IS 3062 02:42:01,450 --> 02:42:09,558 USED TO MODEL THE FUNDAMENTAL 3063 02:42:09,558 --> 02:42:20,102 PREDICTION AND THE OTHER GROUP 3064 02:42:37,853 --> 02:42:41,924 HAD HIGH PROTEIN LOW FAT SUGAR 3065 02:42:41,924 --> 02:42:44,393 AND WE TOOK A SAMPLE AND WEIGHED 3066 02:42:44,393 --> 02:42:45,961 THEM AND AT POST TEST WE REPEAT 3067 02:42:45,961 --> 02:42:46,829 THE STUDIES. 3068 02:42:46,829 --> 02:42:48,230 AND FIRST OF ALL WHAT YOU CAN 3069 02:42:48,230 --> 02:42:51,066 SEE HERE IS THERE WAS NO CHANGE 3070 02:42:51,066 --> 02:42:57,539 IN ADIPOSITY OR MED METABOLIC 3071 02:42:57,539 --> 02:42:59,141 MATTERS AND NOTHING IS 3072 02:42:59,141 --> 02:43:00,442 SIGNIFICANT ACROSS THE TIMES. 3073 02:43:00,442 --> 02:43:02,311 IN THE ANIMAL STUDIES THERE'S NO 3074 02:43:02,311 --> 02:43:04,413 CHANGE IN ADIPOSITY. 3075 02:43:04,413 --> 02:43:05,914 WE WANTED THIS TO BE A DIETARY 3076 02:43:05,914 --> 02:43:06,982 MANIPULATION. 3077 02:43:06,982 --> 02:43:09,551 THOUGH THERE WAS NO CHANGE IN 3078 02:43:09,551 --> 02:43:11,286 ADIPOSITY OR METABOLISM YOU CAN 3079 02:43:11,286 --> 02:43:13,989 SEE THE HIGH FAT-HIGH SUGAR 3080 02:43:13,989 --> 02:43:15,924 GROUP IN BLUE COMPARED TO THE 3081 02:43:15,924 --> 02:43:20,229 LOW-FAT, LOW SUGAR GROUP AFTER 3082 02:43:20,229 --> 02:43:21,497 THE MANIPULATION REPORTED LIKE 3083 02:43:21,497 --> 02:43:23,499 IT LOW-FAT PUDDINGS LESS THAN 3084 02:43:23,499 --> 02:43:25,567 THE BEGINNING AND WANTING THEM 3085 02:43:25,567 --> 02:43:25,801 LESS. 3086 02:43:25,801 --> 02:43:27,169 THAT'S SIMILAR TO WHAT THEY WERE 3087 02:43:27,169 --> 02:43:28,504 OBSERVING IN MICE WHERE THE 3088 02:43:28,504 --> 02:43:30,973 ANIMALS WERE INDIFFERENT TO THE 3089 02:43:30,973 --> 02:43:41,216 GASTRIC INFUSION OF THE LOW-FAT 3090 02:43:41,216 --> 02:43:48,924 EMULSION AND YOU AND IN THE GRAY 3091 02:43:48,924 --> 02:43:50,492 BARS THERE'S NOT. 3092 02:43:50,492 --> 02:43:52,961 THE PEOPLE WHO HAVE THIS SMALL 3093 02:43:52,961 --> 02:43:55,531 MANIPULATION THEIR BRAIN 3094 02:43:55,531 --> 02:43:57,332 RESPONSE TO FOOD CUES VISUAL AND 3095 02:43:57,332 --> 02:44:01,036 THE TASTE OF THE MILK SHAKE IS 3096 02:44:01,036 --> 02:44:03,539 ENHANCED. 3097 02:44:03,539 --> 02:44:10,045 IN THE MID BRAIN AND PREFRONTAL 3098 02:44:10,045 --> 02:44:11,480 CORTEX AND RESPONSE WHEN THEY 3099 02:44:11,480 --> 02:44:16,818 RECEIVE THE HILL -- MILK SHAKE 3100 02:44:16,818 --> 02:44:19,655 AND YOU'RE HEARING A TONE AND 3101 02:44:19,655 --> 02:44:20,689 INDICATING IF YOU THINK YOU'LL 3102 02:44:20,689 --> 02:44:23,225 SEE A FACE OR PLACE AND WE USED 3103 02:44:23,225 --> 02:44:27,229 THIS MODELLING TO EXTRACT THE 3104 02:44:27,229 --> 02:44:28,497 PREDICTION ERROR CODE AND LOOK 3105 02:44:28,497 --> 02:44:29,765 AT THE SENSITIVITY OF TRACKING 3106 02:44:29,765 --> 02:44:37,139 BEFORE AND AFTER THE DIET. 3107 02:44:37,139 --> 02:44:39,741 AND INDIVIDUAL TRACKING AND 3108 02:44:39,741 --> 02:44:41,443 LEARNING SIGNAL WHICH IS 3109 02:44:41,443 --> 02:44:42,444 DOPAMINE DEPENDENT IS ENHANCED 3110 02:44:42,444 --> 02:44:47,249 AND THERE'S ENHANCED TRACKING OF 3111 02:44:47,249 --> 02:44:48,383 PREDICTION OF THIS LEARNING 3112 02:44:48,383 --> 02:44:48,650 SIGNAL. 3113 02:44:48,650 --> 02:44:51,553 NOTHING WHATSOEVER TO DO WITH 3114 02:44:51,553 --> 02:44:53,255 FEEDING SUGGESTING THIS 3115 02:44:53,255 --> 02:44:55,757 MANIPULATION CHANGES AT A 3116 02:44:55,757 --> 02:44:56,491 GENERAL LEVEL DOPAMINE 3117 02:44:56,491 --> 02:44:58,493 SIGNALLING IN HUMANS. 3118 02:44:58,493 --> 02:45:00,329 AND WHETHER OR NOT OF COURSE 3119 02:45:00,329 --> 02:45:06,335 THIS IS RELATED TO BLUNTING OF 3120 02:45:06,335 --> 02:45:09,871 THE TONIC SIGNAL RELATED TO 3121 02:45:09,871 --> 02:45:13,242 POSTSIGNAL IS SOMETHING WE'RE 3122 02:45:13,242 --> 02:45:14,543 LOOKING AT NOW WITH PET AND MRI 3123 02:45:14,543 --> 02:45:15,577 AND THE LAST THING I WANT TO 3124 02:45:15,577 --> 02:45:18,680 SHOW YOU IS THE OBA. 3125 02:45:18,680 --> 02:45:21,583 THIS IS A LARGE CLINICAL TRIAL 3126 02:45:21,583 --> 02:45:24,219 WE'RE IN THE MIDDLE OF AN 3127 02:45:24,219 --> 02:45:29,524 NIH-FUNDED STUDY LOOKING AT OEA 3128 02:45:29,524 --> 02:45:32,461 VERSE YOU PLACEBO WITH 3129 02:45:32,461 --> 02:45:35,931 INDIVIDUALS OVERWEIGHT OR OBESE 3130 02:45:35,931 --> 02:45:38,867 AND TRYING TO SEE IF IT CAN 3131 02:45:38,867 --> 02:45:39,534 REVERSE THE CONDITION IN MICE 3132 02:45:39,534 --> 02:45:41,570 AND I CAN SHOW YOU DATA WE USED 3133 02:45:41,570 --> 02:45:43,138 AS PILOT DATA TO GET THE 3134 02:45:43,138 --> 02:45:44,139 FUNDING. 3135 02:45:44,139 --> 02:45:49,678 WHAT YOU SEE HERE IS A GRAPH OF 3136 02:45:49,678 --> 02:45:52,147 WEIGHT LOSS IN FOUR GROUPS OF 3137 02:45:52,147 --> 02:45:54,149 INDIVIDUALS AND FOCUS ON THE 3138 02:45:54,149 --> 02:45:55,917 ORANGE AND RED LINES BECAUSE 3139 02:45:55,917 --> 02:45:57,119 THESE PEOPLE WERE SUPPLEMENTING 3140 02:45:57,119 --> 02:46:01,223 WITH THE PRECURSOR WITH OEA AND 3141 02:46:01,223 --> 02:46:02,057 OVER 36 WEEKS. 3142 02:46:02,057 --> 02:46:07,162 BOTH GROUPS THE RED AND ORANGE 3143 02:46:07,162 --> 02:46:11,033 ARE RECEIVING THE PHOSPHOLINE 3144 02:46:11,033 --> 02:46:12,701 AND THERE WAS BEHAVIORAL WEIGHT 3145 02:46:12,701 --> 02:46:13,869 LOSS INTERVENTION HERE. 3146 02:46:13,869 --> 02:46:15,537 WHAT YOU YOU CAN CLEARLY SEE IS 3147 02:46:15,537 --> 02:46:18,006 THE INDIVIDUALS IN THE RED LINE 3148 02:46:18,006 --> 02:46:19,274 THOSE ARE THE PEOPLE WOULD AT 3149 02:46:19,274 --> 02:46:21,677 THE BEGINNING WHEN THEY ENROLLED 3150 02:46:21,677 --> 02:46:25,113 IN THE STUDY FOOD DIARIES 3151 02:46:25,113 --> 02:46:26,415 INDICATED THEY WERE FREQUENT 3152 02:46:26,415 --> 02:46:28,450 HIGH FAT FOOD CONSUMERS AND IN 3153 02:46:28,450 --> 02:46:30,285 ORANGE PEOPLE WERE NOT EATING A 3154 02:46:30,285 --> 02:46:34,323 LOT OF SATURATED FAT AND THE OEA 3155 02:46:34,323 --> 02:46:37,759 IS DIFFERENTLY EFFECTIVE SO IF 3156 02:46:37,759 --> 02:46:44,599 YOU HAVE A HIGH-FAT DIET AND 3157 02:46:44,599 --> 02:46:45,867 BLUNTING THAT CAN HELP WITH 3158 02:46:45,867 --> 02:46:47,836 WEIGHT LOSS OUTCOME AND HAVE 3159 02:46:47,836 --> 02:46:50,005 DONE A SMALL STUDY WITH ALCOHOL 3160 02:46:50,005 --> 02:46:53,842 USE DISORDER LOOKING AT DOPAMINE 3161 02:46:53,842 --> 02:46:55,811 DEPENDENT BEHAVIORS AND THIS 3162 02:46:55,811 --> 02:46:57,913 FALSE ALARM RATE WENT DOWN IN 3163 02:46:57,913 --> 02:46:59,514 INDIVIDUALS SUPPLEMENTING 3164 02:46:59,514 --> 02:47:00,816 RELATED TO MAXIMUM DRINKS PER 3165 02:47:00,816 --> 02:47:01,350 DAY. 3166 02:47:01,350 --> 02:47:03,552 THIS IS POTENTIALLY AN 3167 02:47:03,552 --> 02:47:07,222 INTERESTING GUT-BRAIN TARGET FOR 3168 02:47:07,222 --> 02:47:10,759 WEIGHT LOSS BUT ALSO POTENTIALLY 3169 02:47:10,759 --> 02:47:13,595 FOR OTHER CONDITIONS IN WHICH 3170 02:47:13,595 --> 02:47:15,564 THERE'S ADAPTATIONS IN THE 3171 02:47:15,564 --> 02:47:22,771 DOPAMINE SYSTEM AND TO THANK MY 3172 02:47:22,771 --> 02:47:23,438 COLLABORATORS AND THE INSTITUTE 3173 02:47:23,438 --> 02:47:25,907 AND THE NIH FOR FUNDING AND IT 3174 02:47:25,907 --> 02:47:36,318 YOU FOR YOUR ATTENTION. 3175 02:47:38,220 --> 02:47:48,430 >> NO QUESTIONS? 3176 02:48:02,878 --> 02:48:05,947 AND DR. GARFINKEL. 3177 02:48:05,947 --> 02:48:07,382 >> SUCH A PLEASURE TO BE HERE 3178 02:48:07,382 --> 02:48:09,217 AND HEAR SO MANY AMAZING TALKS. 3179 02:48:09,217 --> 02:48:10,652 TODAY I'M GOING TO TALK TO YOU 3180 02:48:10,652 --> 02:48:17,926 ABOUT A CLINICAL TRIAL WE 3181 02:48:17,926 --> 02:48:22,297 DEVISED TO ENHANCE INDIVIDUAL'S 3182 02:48:22,297 --> 02:48:25,901 ON THE AUTISM SPECTRUM 3183 02:48:25,901 --> 02:48:29,538 CONDITIONS ON NEURODEVELOPMENT 3184 02:48:29,538 --> 02:48:34,276 CONDITIONS DISPLAYING AND 3185 02:48:34,276 --> 02:48:37,913 DIFFICULTIES IN EMOTION 3186 02:48:37,913 --> 02:48:45,554 RECOGNITION AND ANXIETY HIGH UP 3187 02:48:45,554 --> 02:48:51,560 AUTISM SPECTRUM DISORDER 23-60% 3188 02:48:51,560 --> 02:49:00,535 AND THE SENSORY LOOKING AT THE 3189 02:49:00,535 --> 02:49:02,070 SENSITIVITY TO LIGHT, SOUNDS AND 3190 02:49:02,070 --> 02:49:07,275 ALSO EMERGING EVIDENCE 3191 02:49:07,275 --> 02:49:09,778 INTEROCEPTION MAYBE ALTERED. 3192 02:49:09,778 --> 02:49:12,547 INDIVIDUALS AUTISTIC WILL HAVE A 3193 02:49:12,547 --> 02:49:15,817 LOT OF SOMATIC COMPLAINTS 3194 02:49:15,817 --> 02:49:21,156 SUGGESTING THE HYPERSENSITIVITY 3195 02:49:21,156 --> 02:49:23,024 TO INTEROCEPTIVE KEYS AND 3196 02:49:23,024 --> 02:49:27,329 FEATURES OF AUTISM ARE ACTUALLY 3197 02:49:27,329 --> 02:49:32,534 CONSISTENT WITH REDUCED 3198 02:49:32,534 --> 02:49:33,568 SENSITIVITY SUCH AS THE REDUCED 3199 02:49:33,568 --> 02:49:37,072 CAPACITY TO UNDERSTAND EMOTIONS, 3200 02:49:37,072 --> 02:49:41,776 DIFFERENCES IN HUNGER AND 3201 02:49:41,776 --> 02:49:43,879 SOCIETY AND SHARED DECISION 3202 02:49:43,879 --> 02:49:49,718 MAKING WHICH CAN BE GUIDED BY 3203 02:49:49,718 --> 02:49:51,152 INTEROCEPTIVE KEYS AND KIDS 3204 02:49:51,152 --> 02:49:53,722 DON'T ALL KNOW WHEN THEY NEED TO 3205 02:49:53,722 --> 02:50:03,398 GO TO THE BATH ROOM ROOM AN 3206 02:50:03,398 --> 02:50:04,799 INTEROCEPTIVE SENSE AND WE'VE 3207 02:50:04,799 --> 02:50:07,702 LOOKED AT SUBJECTIVE AND 3208 02:50:07,702 --> 02:50:09,504 BEHAVIORAL MEASURES OF 3209 02:50:09,504 --> 02:50:09,838 INTEROCEPTION. 3210 02:50:09,838 --> 02:50:17,612 IF YOU ASK SOMEONE HOW OR HOW 3211 02:50:17,612 --> 02:50:20,348 AWARE YOU ARE TO INTEROCEPTION 3212 02:50:20,348 --> 02:50:23,151 THE DOESN'T ALIGN AND SOMETHING 3213 02:50:23,151 --> 02:50:24,185 THAT FASCINATES ME IS PEOPLE 3214 02:50:24,185 --> 02:50:26,855 DON'T HAVE INSIGHTS INTO HOW 3215 02:50:26,855 --> 02:50:27,589 ACCURATE THEY ARE. 3216 02:50:27,589 --> 02:50:30,926 SO AUTISTIC INDIVIDUALS WILL SAY 3217 02:50:30,926 --> 02:50:33,595 THEY'RE VERY AWARE OF 3218 02:50:33,595 --> 02:50:34,963 INTEROCEPTIVE SENSATIONS BUT IF 3219 02:50:34,963 --> 02:50:38,366 YOU MEASURE THE ACCURACY IN THE 3220 02:50:38,366 --> 02:50:43,939 LAB THEY MAY HAVE LOW AC RAS 3221 02:50:43,939 --> 02:50:47,943 YO -- ACCURACY AND SEE IT'S 3222 02:50:47,943 --> 02:50:57,552 CORAL ED -- CORRELATED TO LOWER 3223 02:50:57,552 --> 02:51:00,288 SENSITIVE AND WE DEVISED 3224 02:51:00,288 --> 02:51:01,923 TRAINING IN 160 INDIVIDUALS AND 3225 02:51:01,923 --> 02:51:03,558 TAUGHT THEM TO BE MORE ACCURATE 3226 02:51:03,558 --> 02:51:05,560 AT DETECT BEING CARDIAC 3227 02:51:05,560 --> 02:51:05,860 SENSATIONS. 3228 02:51:05,860 --> 02:51:08,430 IN THE SUBSET OF INDIVIDUALS WE 3229 02:51:08,430 --> 02:51:09,397 SCANNED THEIR BRAINS BEFORE AND 3230 02:51:09,397 --> 02:51:12,801 AFTER TO LOOK AT THE CHANGES IN 3231 02:51:12,801 --> 02:51:14,002 BRAIN CONNECTIVITY AND LOOKED AT 3232 02:51:14,002 --> 02:51:18,340 CHANGES IN ANXIETY. 3233 02:51:18,340 --> 02:51:19,641 WE COMPARED THESE INDIVIDUALS TO 3234 02:51:19,641 --> 02:51:23,612 AN ACTIVE CONTROL GROUP OF 3235 02:51:23,612 --> 02:51:24,079 AUTISTIC INDIVIDUALS. 3236 02:51:24,079 --> 02:51:26,348 NOW THEY'LL OFTEN SAY THEY FELT 3237 02:51:26,348 --> 02:51:28,583 ANXIOUS NOT KNOWING WHAT EMOTION 3238 02:51:28,583 --> 02:51:29,918 THE OTHER PERSON'S FEELING. 3239 02:51:29,918 --> 02:51:37,292 THIS ACTIVE CONTROL WE TAUGHT 3240 02:51:37,292 --> 02:51:38,960 THEM WILL RECOGNITION WHEN IT'S 3241 02:51:38,960 --> 02:51:43,131 SAID IN A SAD OR ANGRY WAY AND 3242 02:51:43,131 --> 02:51:44,099 HELPED THEM UNDERSTAND THE 3243 02:51:44,099 --> 02:51:47,502 SPEECH EN OTHER AS A TRAINING TO 3244 02:51:47,502 --> 02:51:53,241 REDUCE ANXIETY. 3245 02:51:53,241 --> 02:51:55,310 AND FOR OUR INTEROCEPTIVE 3246 02:51:55,310 --> 02:51:57,912 TRAINING WE GOT INDIVIDUAL TO DO 3247 02:51:57,912 --> 02:52:01,316 EXERCISE AS A MEANS TO MAKE THE 3248 02:52:01,316 --> 02:52:06,988 CONTACT SIGNAL MORE OBVIOUS. 3249 02:52:06,988 --> 02:52:11,092 THEN WE GAVE THEM HAS TO TASKS 3250 02:52:11,092 --> 02:52:12,427 WELL USED IN THE LITERATURE. 3251 02:52:12,427 --> 02:52:15,096 ONE IS THE DETECTION TASK WHERE 3252 02:52:15,096 --> 02:52:17,732 INDIVIDUALS SILENTLY COUNT HOW 3253 02:52:17,732 --> 02:52:21,736 MANY HEART BAEM 3254 02:52:24,406 --> 02:52:27,542 HEARTBEATS THEY FEEL AND HOW 3255 02:52:27,542 --> 02:52:30,311 ACCURATE THEY WERE TO JUDGE THE 3256 02:52:30,311 --> 02:52:30,645 SYNCHRONICITY. 3257 02:52:30,645 --> 02:52:33,848 THIS IS A REALLY IMPORTANT TASK 3258 02:52:33,848 --> 02:52:38,920 BECAUSE THE FREQUENCY OF THE 3259 02:52:38,920 --> 02:52:41,790 TONES ARE THE SAME IRRESPECTIVE 3260 02:52:41,790 --> 02:52:43,792 WHETHER THEY'RE IN SYNC OR OUT 3261 02:52:43,792 --> 02:52:47,529 OF SYNC AND NOTHING THAT ALLOWS 3262 02:52:47,529 --> 02:52:55,370 THEM DO THIS NO HIGHER ORDER 3263 02:52:55,370 --> 02:53:00,308 HEART RATE AND SO IT'S VERY 3264 02:53:00,308 --> 02:53:01,910 DIFFICULT. 3265 02:53:01,910 --> 02:53:05,380 THEY HAD HEIGHTENED 3266 02:53:05,380 --> 02:53:08,516 INTEROCEPTIVE FEEDBACK AND WE 3267 02:53:08,516 --> 02:53:14,122 GAVE THEM EXETERO CEPTIVE 3268 02:53:14,122 --> 02:53:24,299 FEEDBACK. 3269 02:53:25,533 --> 02:53:26,668 AND THIS TRAINING WHILE THE 3270 02:53:26,668 --> 02:53:28,203 HEART RATE COMES BACK TO REST. 3271 02:53:28,203 --> 02:53:38,747 IDEA THEY SHOULD BE ABLE TO TEST 3272 02:53:46,721 --> 02:53:53,228 THIS FOLLOWING TRAINING WE 3273 02:53:53,228 --> 02:53:55,063 REPEATED THIS INTEROCEPTIVE 3274 02:53:55,063 --> 02:53:56,798 TRAINING SIX TIMES WITH 3275 02:53:56,798 --> 02:53:59,501 30-MINUTE SESSIONS. 3276 02:53:59,501 --> 02:54:02,036 IN TERMS OF INTEROCEPTIVE 3277 02:54:02,036 --> 02:54:07,142 ACCURACY, ADIE IS STANDS FOR 3278 02:54:07,142 --> 02:54:09,144 ALIGNING INTERVENTIONS OF 3279 02:54:09,144 --> 02:54:11,012 INTEROCEPTIVE EXPERIENCE AND OUR 3280 02:54:11,012 --> 02:54:16,551 MEASURE ON THE Y AXIS IS FOR THE 3281 02:54:16,551 --> 02:54:22,690 IN SYNC-OUT OF SYNC TEST AND 3282 02:54:22,690 --> 02:54:25,927 IT'S A STRINGENT MEASURE AND 3283 02:54:25,927 --> 02:54:29,364 WERE ABLE TO ENHANCE 3284 02:54:29,364 --> 02:54:33,535 INTEROCEPTIVE ACCURACY IN OUR 3285 02:54:33,535 --> 02:54:43,812 TRAINING GROUP. 3286 02:54:47,182 --> 02:54:53,388 AND THE ONE-YEAR DATA ALSO 3287 02:54:53,388 --> 02:54:57,091 MAINTAINED AND HAD A 3288 02:54:57,091 --> 02:54:58,092 PREREGISTERED THRESHOLD WE 3289 02:54:58,092 --> 02:55:01,796 CALLED RECOVERY IN THE SENSE WE 3290 02:55:01,796 --> 02:55:04,632 QUANTIFIED A CLINICALLY 3291 02:55:04,632 --> 02:55:06,601 MEANINGFUL DRUG AND MADE THE 3292 02:55:06,601 --> 02:55:08,736 BELOW THRESHOLD. 3293 02:55:08,736 --> 02:55:12,040 ACCORDING TO THIS PRE REGISTERED 3294 02:55:12,040 --> 02:55:15,443 CRITERION A THIRD OF OUR 3295 02:55:15,443 --> 02:55:17,679 TRAINING GROUP MET THIS 3296 02:55:17,679 --> 02:55:20,114 CRITERION AND HALF OF OUR 3297 02:55:20,114 --> 02:55:20,682 CONTROL INDIVIDUALS. 3298 02:55:20,682 --> 02:55:22,550 WHAT THIS SUGGESTS TO ME IS 3299 02:55:22,550 --> 02:55:25,920 WHILE YOU DO SEE MODEST DROPS OF 3300 02:55:25,920 --> 02:55:27,422 ANXIETY WHICH IS SIGNIFICANT AT 3301 02:55:27,422 --> 02:55:28,823 THE GROUP LEVEL ACTUALLY THERE'S 3302 02:55:28,823 --> 02:55:30,725 PROBABLY A THIRD OF INDIVIDUALS 3303 02:55:30,725 --> 02:55:32,193 THAT THIS REALLY HELPS. 3304 02:55:32,193 --> 02:55:34,796 AND THIS REMINDS ME OF OVER 3305 02:55:34,796 --> 02:55:38,633 ANALYSES SUCH AS DEPRESSION AND 3306 02:55:38,633 --> 02:55:39,734 INFLAMMATION AND MAYBE THERE'S A 3307 02:55:39,734 --> 02:55:43,171 THIRD OF INDIVIDUALS WHERE THE 3308 02:55:43,171 --> 02:55:45,540 INTEROCEPTIVE PROCESSES IN 3309 02:55:45,540 --> 02:55:47,308 ANXIETY MAY BE WAY TO HELP THEM 3310 02:55:47,308 --> 02:55:49,677 WHEN WE DIRECTLY TARGET THEM. 3311 02:55:49,677 --> 02:55:53,181 IN TERMS OF THE PRE-POST 3312 02:55:53,181 --> 02:55:55,283 NEUROIMAGING STANDING WE SAW 3313 02:55:55,283 --> 02:56:03,625 CHANGES IN FUNCTIONAL CONNECTIST 3314 02:56:03,625 --> 02:56:08,596 -- CONNECTIVITY THINKING OF THE 3315 02:56:08,596 --> 02:56:11,132 EARLIER DATA AND THIS INCREASE 3316 02:56:11,132 --> 02:56:13,468 IN RIGHT INSULAR FUNCTIONAL 3317 02:56:13,468 --> 02:56:17,872 CONNECTIVITY CHANGES CORRELATED 3318 02:56:17,872 --> 02:56:21,542 WITH INCREASED INTEROCEPTIVE 3319 02:56:21,542 --> 02:56:26,714 ACCURACY AND SAW LEFT INSULA 3320 02:56:26,714 --> 02:56:33,554 FUNCTIONALITY AT IN THE REGION 3321 02:56:33,554 --> 02:56:39,193 AND INVOLVED WITH HELPING WITH 3322 02:56:39,193 --> 02:56:41,296 AUTONOMIC CONTROL AND AROUSAL. 3323 02:56:41,296 --> 02:56:44,766 MAYBE THIS IS SOMETHING ABOUT 3324 02:56:44,766 --> 02:56:54,108 CREATING COHERENCE IN OUGHT -- 3325 02:56:54,108 --> 02:56:57,946 AUTONOMIC AROUSALS AND I THOUGHT 3326 02:56:57,946 --> 02:56:59,714 SOME PEOPLE WHO UNDERWENT THE 3327 02:56:59,714 --> 02:57:01,649 STUDY WERE INFORMATIVE. 3328 02:57:01,649 --> 02:57:03,384 ONE INDIVIDUAL REPORTED A 3329 02:57:03,384 --> 02:57:06,754 REDUCTION IN SENSORY OVERLOAD 3330 02:57:06,754 --> 02:57:08,189 SPECIFICALLY THEY SAID AS THE 3331 02:57:08,189 --> 02:57:09,490 INNER CHANNEL GETS CLEARER THE 3332 02:57:09,490 --> 02:57:12,727 OUTER CHANNEL GETS MORE QUIET 3333 02:57:12,727 --> 02:57:15,563 AND AGAIN THIS MADE ME THINK OF 3334 02:57:15,563 --> 02:57:20,702 WHEN YOU CREATE SENSORY THAT 3335 02:57:20,702 --> 02:57:22,737 EXTERNAL SENSES YOU GET STRONGER 3336 02:57:22,737 --> 02:57:25,139 INTERNAL SENSES AND IF YOU CAN 3337 02:57:25,139 --> 02:57:27,408 MAKE THIS INTEROCEPTIVE CHANNEL 3338 02:57:27,408 --> 02:57:29,644 STRONGER THEN POTENTIALLY HAVE 3339 02:57:29,644 --> 02:57:36,951 YOU THE POSSIBILITY OF SAMPLING 3340 02:57:36,951 --> 02:57:41,756 EXETER JOE SO SECEPTIVE SENSORY 3341 02:57:41,756 --> 02:57:43,591 REQUIRE MORE HYPOTHESIS TESTING 3342 02:57:43,591 --> 02:57:44,459 IN THE FUTURE AND ANOTHER 3343 02:57:44,459 --> 02:57:46,060 INDIVIDUAL SAID WHEN I NOTICE 3344 02:57:46,060 --> 02:57:49,163 THE IMPACTS OF ANXIETY IN MY 3345 02:57:49,163 --> 02:57:51,599 BODY I'M MORE AWARE AND ABLE TO 3346 02:57:51,599 --> 02:57:58,439 ASSURE MYSELF IT'S JUST A 3347 02:57:58,439 --> 02:58:03,077 PHYSICAL REACTION AND THEY ALSO 3348 02:58:03,077 --> 02:58:04,545 SAID BETTER ABLE AT TAKING DEEP 3349 02:58:04,545 --> 02:58:07,081 BREATHS AND TRYING TO SLOW MY 3350 02:58:07,081 --> 02:58:08,516 HEART RATE DOWN INSTEAD OF 3351 02:58:08,516 --> 02:58:10,351 LETTING IT SPIRAL. 3352 02:58:10,351 --> 02:58:13,187 I THINK IT SPEAKS TO THE 3353 02:58:13,187 --> 02:58:14,489 INTEROCEPTIVE ACCURACY GIVES A 3354 02:58:14,489 --> 02:58:18,192 POTENTIAL FOR CONTROL AT AN 3355 02:58:18,192 --> 02:58:19,761 EARLIER POINT. 3356 02:58:19,761 --> 02:58:21,929 AUTISTIC INDIVIDUALS WILL SAY 3357 02:58:21,929 --> 02:58:24,399 THEY SUDDENLY WERE OVERWHELMED 3358 02:58:24,399 --> 02:58:28,102 IN A PANIC ATTACK AND IF YOU CAN 3359 02:58:28,102 --> 02:58:29,570 HELP PEOPLE FEEL WHEN THEIR 3360 02:58:29,570 --> 02:58:32,240 HEART RATE STARTING TO 3361 02:58:32,240 --> 02:58:33,908 ACCELERATE IT GIVES AN EARLIER 3362 02:58:33,908 --> 02:58:37,478 TIME POINT REGULATE THE CELLS 3363 02:58:37,478 --> 02:58:39,914 AND SOMEONE SAID I BELIEVE IT 3364 02:58:39,914 --> 02:58:41,916 INCREASED MY AWARENESS OF HUNGER 3365 02:58:41,916 --> 02:58:44,485 AND AS A RESULT I REMEMBER TO GO 3366 02:58:44,485 --> 02:58:48,189 TO TO EAT, DRINK AND GO TO THE 3367 02:58:48,189 --> 02:58:52,393 TOILET AND IT SUGGESTS JUST 3368 02:58:52,393 --> 02:58:55,963 TARGETING ONE INTEROCEPTION 3369 02:58:55,963 --> 02:58:57,899 DIMENSION MAY INFLUENCE OTHER 3370 02:58:57,899 --> 02:59:00,501 AXES AND IT REQUIRES SYSTEMATIC 3371 02:59:00,501 --> 02:59:02,970 INVESTIGATION IN THE FUTURE. 3372 02:59:02,970 --> 02:59:04,238 TO COMPLETE, INTEROCEPTIVE 3373 02:59:04,238 --> 02:59:09,510 TRAINING CAN REDUCE ANXIETY IN 3374 02:59:09,510 --> 02:59:11,979 AUTISTIC ADULTS AND EXTENDED 3375 02:59:11,979 --> 02:59:13,915 THIS TO A NON-AUTISTIC 3376 02:59:13,915 --> 02:59:16,617 POPULATION AND COULD HELP 3377 02:59:16,617 --> 02:59:20,054 NON-AUTISTIC INDIVIDUALS MANAGE 3378 02:59:20,054 --> 02:59:22,723 ANXIETY AND HELP INDIVIDUALS. 3379 02:59:22,723 --> 02:59:27,728 AND WE SHOWED ENHANCED INTERO 3380 02:59:27,728 --> 02:59:29,597 CHANGES INVOLVED IN 3381 02:59:29,597 --> 02:59:30,231 INTEROCEPTION AND MADE EMOTION 3382 02:59:30,231 --> 02:59:35,503 REGULATION. 3383 02:59:35,503 --> 02:59:40,508 THANK YOU SO MUCH TO HUGO 3384 02:59:40,508 --> 02:59:43,077 CRITCHLEY AND IT WAS SO MUCH 3385 02:59:43,077 --> 02:59:47,648 WORK AND WE DID IT TOGETHER AND 3386 02:59:47,648 --> 02:59:49,484 THANK YOU FOR THE TEAMS AND 3387 02:59:49,484 --> 02:59:50,284 FUNDING AGENCIES AND THANK YOU 3388 02:59:50,284 --> 02:59:59,127 FOR LISTENING. 3389 02:59:59,127 --> 03:00:00,128 >> THANK YOU. 3390 03:00:00,128 --> 03:00:01,129 THAT WAS TERRIFIC. 3391 03:00:01,129 --> 03:00:04,298 THERE'S A QUESTION MAYBE BEFORE 3392 03:00:04,298 --> 03:00:07,969 THE QUESTION I THINK WHAT WE'LL 3393 03:00:07,969 --> 03:00:08,970 DO IS TAKE THE QUESTION AND OPEN 3394 03:00:08,970 --> 03:00:11,672 IT UP TO QUESTIONS FOR THE REST 3395 03:00:11,672 --> 03:00:12,707 OF THE SPEAKERS. 3396 03:00:12,707 --> 03:00:16,110 I KNOW WE'RE GETTING CLOSE TO 3397 03:00:16,110 --> 03:00:20,214 LUNCH AND WE DON'T WANT TO STAND 3398 03:00:20,214 --> 03:00:22,450 TOO MUCH IN BETWEEN YOU AND 3399 03:00:22,450 --> 03:00:24,752 LUNCH AND MAYBE GO 10 MINUTES 3400 03:00:24,752 --> 03:00:27,555 INTO THE BREAK AND THEN WRAP UP. 3401 03:00:27,555 --> 03:00:33,561 >> GREAT WORK, CONGRATULATIONS. 3402 03:00:33,561 --> 03:00:36,831 >> GEORGE WASHINGTON UNIVERSITY. 3403 03:00:36,831 --> 03:00:39,534 MY FIRST QUESTION WAS THE 3404 03:00:39,534 --> 03:00:44,238 APPLICABILITY OUTSIDE OF 3405 03:00:44,238 --> 03:00:45,106 AUTISTIC INDIVIDUALS WHICH IS 3406 03:00:45,106 --> 03:00:48,809 EXCITING AND MY SECOND QUESTION 3407 03:00:48,809 --> 03:00:59,353 IS WHETHER OR NOT YOU CAN HELP 3408 03:01:10,064 --> 03:01:11,098 WITH ANXIETY. 3409 03:01:11,098 --> 03:01:13,267 >> WE FOCUSSED ON BRAIN METRICS 3410 03:01:13,267 --> 03:01:16,237 TO LOOK AT CHANGE BUT WE HAVE 3411 03:01:16,237 --> 03:01:19,473 CARDIAC DATA SUCH AS HEART RATE 3412 03:01:19,473 --> 03:01:21,042 AND HEART RATE VARIABILITY WE'VE 3413 03:01:21,042 --> 03:01:23,211 NOT LOOKED AT SYSTEMATICALLY 3414 03:01:23,211 --> 03:01:23,377 YET. 3415 03:01:23,377 --> 03:01:25,913 I CAN'T SPEAK TO THAT. 3416 03:01:25,913 --> 03:01:28,583 WE'RE ABOUT TO DO MORE TRAINING 3417 03:01:28,583 --> 03:01:31,419 GOT A TRAINING AND LOOKING AT 3418 03:01:31,419 --> 03:01:33,421 GASTRIC, RESPIRATORY AND CARDIAC 3419 03:01:33,421 --> 03:01:35,690 AND DOING MORE DETAILED 3420 03:01:35,690 --> 03:01:36,724 CHARACTERIZATIONS AND HOPE TO 3421 03:01:36,724 --> 03:01:38,025 LOOK AT PERIPHERAL MEASURES IN 3422 03:01:38,025 --> 03:01:39,994 GREATER DETAIL. 3423 03:01:39,994 --> 03:01:41,262 I HOPE THAT'S SOMETHING TO SPEAK 3424 03:01:41,262 --> 03:01:51,806 TO IN MORE DETAIL IN THE FUTURE. 3425 03:01:57,245 --> 03:01:59,947 >> THERE'S MICROPHONES ON THE 3426 03:01:59,947 --> 03:02:09,423 SIDE OF THE ROOM. 3427 03:02:09,423 --> 03:02:15,396 >> GREAT SET OF TALKS. 3428 03:02:15,396 --> 03:02:17,298 I'M AN ASSOCIATE PROFESSOR AT 3429 03:02:17,298 --> 03:02:20,368 THE UNIVERSITY OF BALTIMORE. 3430 03:02:20,368 --> 03:02:23,237 DR. GARFINKEL YOU SAID ANXIETY 3431 03:02:23,237 --> 03:02:25,206 WAS MISMATCHED BETWEEN SOMEONE'S 3432 03:02:25,206 --> 03:02:28,042 PERCEIVED ACCURACY AND ACTUAL 3433 03:02:28,042 --> 03:02:28,309 ACCURACY. 3434 03:02:28,309 --> 03:02:29,210 CAN YOU TALK ABOUT DID YOU LOOK 3435 03:02:29,210 --> 03:02:33,581 AT THAT AS AN OUTCOME AS A 3436 03:02:33,581 --> 03:02:36,851 RESULT OF YOUR TRAINING AND 3437 03:02:36,851 --> 03:02:40,388 WHETHER DID THE ACCURACY AND 3438 03:02:40,388 --> 03:02:42,857 MISMATCH BETWEEN ACTUAL AND 3439 03:02:42,857 --> 03:02:45,092 PERCEIVED ACCURACY CONTRIBUTE TO 3440 03:02:45,092 --> 03:02:46,527 INDEPENDENT AND CAN YOU COMMENT. 3441 03:02:46,527 --> 03:02:47,528 >> IT'S AN INTERESTING QUESTION. 3442 03:02:47,528 --> 03:02:49,664 IF I HAD MORE TIME I WOULD HAVE 3443 03:02:49,664 --> 03:02:53,334 PUT IN WHAT IS MY FAVORITE SLIDE 3444 03:02:53,334 --> 03:02:57,038 WHICH IS SHOWING THIS AWARENESS 3445 03:02:57,038 --> 03:02:59,040 MEASURE WE ASKED HOW AWARE ARE 3446 03:02:59,040 --> 03:03:02,043 YOU OF THE SENSATION AND THAT'S 3447 03:03:02,043 --> 03:03:05,880 WHAT WE USE AS OUR SUBJECTIVE 3448 03:03:05,880 --> 03:03:07,715 MEASURE FOR THE MISMATCH. 3449 03:03:07,715 --> 03:03:09,583 PEOPLE WHO BECOME MORE ACCURATE 3450 03:03:09,583 --> 03:03:11,185 SUBSEQUENTLY REPORT BEING LESS 3451 03:03:11,185 --> 03:03:13,421 AWARE WHICH FIND ENDLESS I 3452 03:03:13,421 --> 03:03:13,721 FASCINATING. 3453 03:03:13,721 --> 03:03:17,391 YOU CAN ACCOUNT FOR IT IN A 3454 03:03:17,391 --> 03:03:22,163 PREDICTED POSING WAY BUT IF 3455 03:03:22,163 --> 03:03:26,801 PEOPLE ARE MONITORING A LOT AND 3456 03:03:26,801 --> 03:03:29,036 HAVE STRONG BELIEFS WITH THE 3457 03:03:29,036 --> 03:03:30,638 BODY OR THEY HAVE PRODUCED 3458 03:03:30,638 --> 03:03:32,340 PRECISION THEN MAYBE THEY NEED 3459 03:03:32,340 --> 03:03:33,574 TO USE POTENTIAL RESOURCES 3460 03:03:33,574 --> 03:03:35,576 BECAUSE THEY HAVE TO USE 3461 03:03:35,576 --> 03:03:36,010 PRECISION. 3462 03:03:36,010 --> 03:03:37,278 IF YOU CAN INCREASE THE 3463 03:03:37,278 --> 03:03:38,579 PRECISION THEN THEY'RE ABLE TO 3464 03:03:38,579 --> 03:03:40,147 PAY ATTENTION TO THAT WHEN IT'S 3465 03:03:40,147 --> 03:03:41,716 MEANINGFULLY CHANGED. 3466 03:03:41,716 --> 03:03:45,252 IT TAKES UP LESS MONITORING AND 3467 03:03:45,252 --> 03:03:45,853 RESOURCES. 3468 03:03:45,853 --> 03:03:48,556 WE DO FIND THIS BEAUTIFUL 3469 03:03:48,556 --> 03:03:49,957 OPPOSITE DIRECTION SO IT'S 3470 03:03:49,957 --> 03:03:53,361 LOVELY EFFECTIVE ACCURACY 3471 03:03:53,361 --> 03:03:55,496 INCREASE AND MONITORING 3472 03:03:55,496 --> 03:03:57,565 DECREASES AND TO THE GAP ALSO 3473 03:03:57,565 --> 03:04:03,337 DOES REDUCE. 3474 03:04:03,337 --> 03:04:04,939 >> WAYNE STATE UNIVERSITY IN 3475 03:04:04,939 --> 03:04:05,873 DETROIT. 3476 03:04:05,873 --> 03:04:07,341 DRAET PRESENTATIONS FROM ALL -- 3477 03:04:07,341 --> 03:04:08,609 GREAT PRESENTATIONS FROM ALL OF 3478 03:04:08,609 --> 03:04:14,281 YOU BUT A QUESTION FROM STANFORD 3479 03:04:14,281 --> 03:04:16,984 BEING A CLINICIAN, THESE 3480 03:04:16,984 --> 03:04:22,390 FINDINGS EXPLAIN WHY DRUGS THAT 3481 03:04:22,390 --> 03:04:25,559 ACROSS THE BLOOD-BRAIN BARRIER 3482 03:04:25,559 --> 03:04:30,231 ARE BETA BLOCKERS LIKE ATENOLOL 3483 03:04:30,231 --> 03:04:38,639 THAT DON'T CROSS THE BLOOD BRAIN 3484 03:04:38,639 --> 03:04:42,309 BARRIERS AND SHOULD WE TREAT 3485 03:04:42,309 --> 03:04:44,879 WITH THOSE THAT REDUCE HEART 3486 03:04:44,879 --> 03:04:50,684 RATE FOR ANXIETY? 3487 03:04:50,684 --> 03:05:00,928 >> THANK YOU. 3488 03:05:02,430 --> 03:05:06,467 AND WHATEVER SERVICE THEY'RE ON, 3489 03:05:06,467 --> 03:05:09,570 ICU, NEUROLOGY SERVICE AND 3490 03:05:09,570 --> 03:05:11,739 PATIENTS WHO ARE ANXIOUS I WOULD 3491 03:05:11,739 --> 03:05:14,442 AGREE REDUCING HEART RATE SHOULD 3492 03:05:14,442 --> 03:05:19,447 BE CONSIDERED POSSIBLY AS AN 3493 03:05:19,447 --> 03:05:24,718 INTERVENTION IN ITS OWN RIGHT TO 3494 03:05:24,718 --> 03:05:33,928 ADDRESS ANXIETY. 3495 03:05:33,928 --> 03:05:37,932 THAT'S SOMETHING PEOPLE SHOULD 3496 03:05:37,932 --> 03:05:41,469 CONSIDER. 3497 03:05:41,469 --> 03:05:43,704 THERE'S BEEN DRUGS FOR TREATMENT 3498 03:05:43,704 --> 03:05:46,607 BUT WILL LOWER THE HEART RATE 3499 03:05:46,607 --> 03:05:50,010 AND IMPROVE MORBIDITY BUT MAKE 3500 03:05:50,010 --> 03:05:51,846 PATIENTS FEEL BETTER IN QUALITY 3501 03:05:51,846 --> 03:05:52,079 MEASURE. 3502 03:05:52,079 --> 03:06:00,221 >> THANK YOU FOR THAT QUESTION. 3503 03:06:00,221 --> 03:06:04,325 QUE WE DO THINGS THAT WE THINK 3504 03:06:04,325 --> 03:06:05,626 WILL HELP PEOPLE BEFORE AND 3505 03:06:05,626 --> 03:06:09,563 AFTER THE STUDY'S COMPLETED AND 3506 03:06:09,563 --> 03:06:17,705 WORTH TRYING. 3507 03:06:17,705 --> 03:06:19,607 >> THERE'S A DIFFERENCE BETWEEN 3508 03:06:19,607 --> 03:06:22,376 ACUTE AND CHRONIC ANXIETY AND 3509 03:06:22,376 --> 03:06:23,711 THERE'S CONDITIONS WHERE PEOPLE 3510 03:06:23,711 --> 03:06:27,281 HAVE LONG-TERM ANXIETY AND 3511 03:06:27,281 --> 03:06:29,383 TACHYCARDIA IS NOT MUCH OF A 3512 03:06:29,383 --> 03:06:39,860 CONCERN BUT BRADYCARDIA AND 3513 03:06:44,832 --> 03:06:49,837 BENZODIAZEPINES DON'T WORK FOR 3514 03:06:49,837 --> 03:06:55,409 THEM EITHER. 3515 03:06:55,409 --> 03:06:58,979 WHEN YOU THINK OF ACUTE ANXIETY 3516 03:06:58,979 --> 03:07:01,916 MAYBE THERE'S MORE OF A ROLE 3517 03:07:01,916 --> 03:07:06,654 THERE. 3518 03:07:06,654 --> 03:07:10,357 >> I'M A GASTROENTEROLOGIST AT 3519 03:07:10,357 --> 03:07:11,625 UNIVERSITY OF GEORGIA. 3520 03:07:11,625 --> 03:07:16,463 THE VIBRATING CAPSULE IS FDA 3521 03:07:16,463 --> 03:07:19,033 APPROVED FOR CONSTIPATION. 3522 03:07:19,033 --> 03:07:21,569 WHEN YOU DEVELOP POTENTIALS FOR 3523 03:07:21,569 --> 03:07:24,038 THE STOMACH WERE THEY THE SAME 3524 03:07:24,038 --> 03:07:26,273 AS IN THE COLON OR DID YOU CHECK 3525 03:07:26,273 --> 03:07:26,540 THAT? 3526 03:07:26,540 --> 03:07:28,809 >> IT'S NOT FDA APPROVED. 3527 03:07:28,809 --> 03:07:31,111 IT'S JUST ALLOWED FOR MARKETING 3528 03:07:31,111 --> 03:07:32,379 AND NON-SIGNIFICANT RISK DEVICE. 3529 03:07:32,379 --> 03:07:35,382 WE'RE ABLE TO USE IT UNDER THAT 3530 03:07:35,382 --> 03:07:35,616 AUSPICE. 3531 03:07:35,616 --> 03:07:41,622 WE DID START WITH A PLAN TO TO 3532 03:07:41,622 --> 03:07:44,191 LOOK AT VIBRATIONS IN THE 3533 03:07:44,191 --> 03:07:45,559 STOMACH AND OTHER SEQUENCE IN 3534 03:07:45,559 --> 03:07:50,064 THE COLON. 3535 03:07:50,064 --> 03:07:51,465 WHEN WE STARTED THINKING ABOUT 3536 03:07:51,465 --> 03:07:53,867 THE PHYSIOLOGY AT PLAY AND HOW 3537 03:07:53,867 --> 03:07:56,437 EVEN WITHIN A 30-MINUTE TIME 3538 03:07:56,437 --> 03:07:58,572 SPAN THE CAPSULE COULD MOVE OUT 3539 03:07:58,572 --> 03:08:06,780 OF THE STOMACH WAITING FOR THIS 3540 03:08:06,780 --> 03:08:08,782 CAPSULE TO GET IN THE COLON 3541 03:08:08,782 --> 03:08:10,918 AFTER EIGHT HOURS AND WE HAVEN'T 3542 03:08:10,918 --> 03:08:12,720 STARTED WITH OTHER SEGMENTS OF 3543 03:08:12,720 --> 03:08:14,054 THE G.I. TRACT BUT WE'RE AT THE 3544 03:08:14,054 --> 03:08:15,189 BEGINNING STAGES. 3545 03:08:15,189 --> 03:08:17,791 >> IT IS NOW FDA APPROVED FOR 3546 03:08:17,791 --> 03:08:18,125 CONSTIPATION. 3547 03:08:18,125 --> 03:08:28,268 >> OKAY. 3548 03:08:30,871 --> 03:08:33,407 >> I HAVE A QUESTION FOR CARL. 3549 03:08:33,407 --> 03:08:38,278 WHEN YOU DO THE PACING THE HEART 3550 03:08:38,278 --> 03:08:43,050 I WONDER IF YOU SEE A CHANGE IN 3551 03:08:43,050 --> 03:08:43,317 FREQUENCY. 3552 03:08:43,317 --> 03:08:48,455 THE HEART PACING SO BASICALLY MY 3553 03:08:48,455 --> 03:08:49,623 QUESTION IS DO YOU THINK THE 3554 03:08:49,623 --> 03:08:51,158 BRAIN IS SENSE THE CHANGE OF THE 3555 03:08:51,158 --> 03:08:52,493 HEART RATE OR IS IT POSSIBLE 3556 03:08:52,493 --> 03:08:57,898 IT'S SENSING THE CHANGE OF SOME 3557 03:08:57,898 --> 03:09:01,135 OF THE HEART FUNCTIONS? 3558 03:09:01,135 --> 03:09:03,971 >> WHAT OUR INTERVENTION DOES IS 3559 03:09:03,971 --> 03:09:09,576 DIRECTLY CAUSES VENTRICULAR 3560 03:09:09,576 --> 03:09:12,513 CONTRACTION AND IN THAT SETTING 3561 03:09:12,513 --> 03:09:14,481 WE CAN NO LONGER SEE THE WAVES 3562 03:09:14,481 --> 03:09:17,785 THAT WOULD TYPICALLY APPEAR. 3563 03:09:17,785 --> 03:09:19,219 IS THERE A CONSEQUENCE OF THAT 3564 03:09:19,219 --> 03:09:22,990 OR INFORMATION THAT IS SOMEHOW 3565 03:09:22,990 --> 03:09:23,624 TRANSMITTED SENT BACK TO THE 3566 03:09:23,624 --> 03:09:23,824 BRAIN? 3567 03:09:23,824 --> 03:09:29,997 I CAN'T RULE THAT OUT. 3568 03:09:29,997 --> 03:09:37,905 THE VENTRICULAR CONTRACTION CAN 3569 03:09:37,905 --> 03:09:39,540 MANIFEST THROUGH BLOOD PRESSURE 3570 03:09:39,540 --> 03:09:42,643 CHANGES AND POSSIBLE MECHANISMS 3571 03:09:42,643 --> 03:09:48,782 BY WHICH THE EFFECT COULD BE 3572 03:09:48,782 --> 03:09:49,083 MANIFESTED. 3573 03:09:49,083 --> 03:09:52,619 A LOT OF THIS IS ON THE POSTER 3574 03:09:52,619 --> 03:09:54,088 AND HEALING BE FOLLOWING UP A 3575 03:09:54,088 --> 03:09:57,591 LOT OF THESE MECHANISTIC 3576 03:09:57,591 --> 03:09:58,025 QUESTIONS. 3577 03:09:58,025 --> 03:10:03,263 I WILL SAY THE BLOOD PRESSURE I 3578 03:10:03,263 --> 03:10:04,865 TEND TO THINK IS NOT A MECHANISM 3579 03:10:04,865 --> 03:10:08,235 BY WHICH THE EFFECT IS 3580 03:10:08,235 --> 03:10:10,104 TRANSMITTED BACK TO THE BRAIN. 3581 03:10:10,104 --> 03:10:11,538 THAT'S WHERE A NUMBER OF REASONS 3582 03:10:11,538 --> 03:10:17,611 INCLUDING DATA WE PRESENTED IN 3583 03:10:17,611 --> 03:10:21,548 THE PAPER AND OTHER PHARMACOLOGY 3584 03:10:21,548 --> 03:10:22,316 AND THE DIRECTION BLOOD 3585 03:10:22,316 --> 03:10:23,884 PRESSURE'S GOING IN. 3586 03:10:23,884 --> 03:10:25,452 THE PRECISE MECHANISMS LOTS OF 3587 03:10:25,452 --> 03:10:26,320 INTERESTING QUESTIONS WE'RE 3588 03:10:26,320 --> 03:10:27,554 WORKING ON AND WE'LL BE 3589 03:10:27,554 --> 03:10:32,126 FOLLOWING UP ON. 3590 03:10:32,126 --> 03:10:35,262 >> AND ONE MORE OVER HERE. 3591 03:10:35,262 --> 03:10:37,898 >> I'M A POSTDOC AT VANDERBILT. 3592 03:10:37,898 --> 03:10:38,866 I HAVE ANOTHER QUESTION FOR 3593 03:10:38,866 --> 03:10:41,535 DR. GARFINKEL. 3594 03:10:41,535 --> 03:10:43,937 I'M CURIOUS FROM A PRECISION 3595 03:10:43,937 --> 03:10:44,671 MEDICINE STANDPOINT IF THERE'S 3596 03:10:44,671 --> 03:10:46,840 ANY PARTICIPANT FEATURES YOU 3597 03:10:46,840 --> 03:10:52,479 THINK ARE PREDICTING AND THE 3598 03:10:52,479 --> 03:10:55,749 ONE-THIRD OF RESPONDERS. 3599 03:10:55,749 --> 03:10:58,452 >> AND WE'RE DOING COMPUTATIONAL 3600 03:10:58,452 --> 03:11:00,521 MODELS TO TRY AND BUILD UP 3601 03:11:00,521 --> 03:11:03,157 BETTER UNDERSTANDING OF WHAT 3602 03:11:03,157 --> 03:11:04,491 COULD BE MOST PROTECTIVE. 3603 03:11:04,491 --> 03:11:06,460 I DON'T WANT TO SPEAK TOO MUCH 3604 03:11:06,460 --> 03:11:10,531 TO THOSE FINDINGS BUT THERE 3605 03:11:10,531 --> 03:11:14,802 SEEMS TO BE THEY HAVE THIS. 3606 03:11:14,802 --> 03:11:17,437 LOWER PRECISION MEASURE THAT 3607 03:11:17,437 --> 03:11:19,473 SEEMS TO POINT TO SOMETHING 3608 03:11:19,473 --> 03:11:21,074 ABOUT THE PERIPHERY BUT WE'RE 3609 03:11:21,074 --> 03:11:22,910 LOOKING FURTHER INTO IT. 3610 03:11:22,910 --> 03:11:26,346 I'M SORRY I CAN'T ANSWER THAT 3611 03:11:26,346 --> 03:11:29,917 YET AND HOPE TO HAVE BETTER 3612 03:11:29,917 --> 03:11:32,186 ANSWERS SOON BECAUSE I AGREE 3613 03:11:32,186 --> 03:11:33,854 FROM A PRECISION MEDICINE 3614 03:11:33,854 --> 03:11:35,322 PERSPECTIVE THAT'S WHAT WE NEED 3615 03:11:35,322 --> 03:11:36,056 TO UNDERSTAND. 3616 03:11:36,056 --> 03:11:37,925 >> I'LL ASK DR. COLEMAN A 3617 03:11:37,925 --> 03:11:40,828 QUESTION. 3618 03:11:40,828 --> 03:11:42,629 I'M A CLINICAL CARDIOLOGIST. 3619 03:11:42,629 --> 03:11:45,632 A SUBSET OF PATIENTS I SEE HAVE 3620 03:11:45,632 --> 03:11:49,636 THE SAME FUNCTIONAL 3621 03:11:49,636 --> 03:11:50,971 GASTROINTESTINAL COMPLAINTS 3622 03:11:50,971 --> 03:11:52,940 DISCUSSED THEY OFTEN GET 3623 03:11:52,940 --> 03:11:54,775 REFERRED TO CARDIOLOGIST AND THE 3624 03:11:54,775 --> 03:11:57,578 HEART RATES DON'T BEHAVE AS THEY 3625 03:11:57,578 --> 03:11:58,879 SHOULD. 3626 03:11:58,879 --> 03:12:00,881 PARTIALLY SOMETIMES DURING 3627 03:12:00,881 --> 03:12:01,448 ORTHOSTATIC CHANGES. 3628 03:12:01,448 --> 03:12:11,859 WE SEE WHAT'S LABELLED AS A 3629 03:12:11,859 --> 03:12:13,994 DYSAUTONOMIA AND WHERE YOU WERE 3630 03:12:13,994 --> 03:12:17,798 ABLE TO CAPTURE THE HEART RATE 3631 03:12:17,798 --> 03:12:21,368 DID YOU SEE ANYTHING BEYOND 3632 03:12:21,368 --> 03:12:24,338 HEART RATE VARIABILITY WHETHER 3633 03:12:24,338 --> 03:12:26,907 THERE'S DIFFERENCES IN THE 3634 03:12:26,907 --> 03:12:28,242 HEART-RATE RELATED METRICS AND 3635 03:12:28,242 --> 03:12:33,747 THE VISION WITH THE 3636 03:12:33,747 --> 03:12:34,581 GASTROINTESTINAL PARTS. 3637 03:12:34,581 --> 03:12:37,284 >> FIRST I WANT TO RESPOND TO 3638 03:12:37,284 --> 03:12:41,989 THE GENTLEMAN FROM WAYNE STREET, 3639 03:12:41,989 --> 03:12:42,689 GO BLUE. 3640 03:12:42,689 --> 03:12:45,826 BUT WE DID NOT TARGET THAT 3641 03:12:45,826 --> 03:12:48,128 DIRECTLY BUT THE ONE THING THIS 3642 03:12:48,128 --> 03:12:50,097 IS AN AMBULATORY REPORTING WHERE 3643 03:12:50,097 --> 03:12:51,665 PEOPLE WERE GOING AROUND AND NOT 3644 03:12:51,665 --> 03:12:55,669 A CONTROLLED SETTING AND WE'D 3645 03:12:55,669 --> 03:12:57,104 HAVE TO -- WE HAVE AN METER ON 3646 03:12:57,104 --> 03:12:59,172 AND YOU CAN SEE WHEN YOU WENT 3647 03:12:59,172 --> 03:13:02,342 FROM LAYING DOWN, STANDING UP, 3648 03:13:02,342 --> 03:13:05,612 ETCETERA WE HAVE THE DATA BUT 3649 03:13:05,612 --> 03:13:08,448 DIDN'T DIRECTLY TARGET THAT SO I 3650 03:13:08,448 --> 03:13:09,483 APPRECIATE THAT SUGGESTION. 3651 03:13:09,483 --> 03:13:10,150 >> ALL RIGHT. 3652 03:13:10,150 --> 03:13:12,686 JUST BEFORE WE WRAP UP, I WANT 3653 03:13:12,686 --> 03:13:15,455 TO REMIND EVERYBODY WE NOW HAVE 3654 03:13:15,455 --> 03:13:17,257 A TWO-HOUR BREAK. 3655 03:13:17,257 --> 03:13:18,558 WE'RE RUNNING SLIGHTLY LATE BUT 3656 03:13:18,558 --> 03:13:24,231 WE STILL WANT TO COME BACK AT 3657 03:13:24,231 --> 03:13:24,498 12:30. 3658 03:13:24,498 --> 03:13:27,601 AND THE POSTER SESSION WILL BE 3659 03:13:27,601 --> 03:13:30,003 RUNNING CONCURRENTLY -- 2:30, 3660 03:13:30,003 --> 03:13:35,142 SORRY. 3661 03:13:35,142 --> 03:13:45,585 A H, THE POSTERS WITH ODD 3662 03:13:51,658 --> 03:13:55,662 NUMBERS FROM 1:25 AND BEFORE YOU 3663 03:13:55,662 --> 03:13:57,097 YOU DISAPPEAR LET'S HAVE A BIG 3664 03:13:57,097 --> 03:14:00,334 ROUND OF APPLAUSE FOR ALL OF OUR 3665 03:14:00,334 --> 03:14:10,129 SPEAKERS. SEE YOU IN LESS THAN TWO HOURS. 3666 03:14:10,129 --> 03:14:10,329 HELLO. 3667 03:14:10,329 --> 03:14:12,865 IT IS MY PRIVILEGE TO WELCOME 3668 03:14:12,865 --> 03:14:18,237 YOU TO OUR AFTERNOON SESSION ON 3669 03:14:18,237 --> 03:14:19,105 BRAIN-MULTIORGAN SYSTEM 3670 03:14:19,105 --> 03:14:19,405 CONNECTIONS. 3671 03:14:19,405 --> 03:14:22,608 MY NAME IS JULIA BERZHANSKAYA. 3672 03:14:22,608 --> 03:14:25,745 I AM A PROGRAM OFFICER AT THE 3673 03:14:25,745 --> 03:14:27,513 OFFICE OF INNOVATION, NATIONAL 3674 03:14:27,513 --> 03:14:29,382 HEART, LUNG AND BLOOD INSTITUTE, 3675 03:14:29,382 --> 03:14:32,452 AND IN THIS POSITION, I'M 3676 03:14:32,452 --> 03:14:33,986 RESPONSIBLE FOR INITIATIVES 3677 03:14:33,986 --> 03:14:37,724 RELATED TO PRODUCT DEVELOPMENT. 3678 03:14:37,724 --> 03:14:44,697 I WOULD LIKE TO INTRODUCE MY 3679 03:14:44,697 --> 03:14:47,133 CO-MODERATOR, DR. ENTER 3680 03:14:47,133 --> 03:14:52,839 ANDERMANN, A -- DR. ANDERMANN, 3681 03:14:52,839 --> 03:14:53,840 AT HARVARD MEDICAL SCHOOL. 3682 03:14:53,840 --> 03:14:55,775 >> HI, EVERYBODY, WE'VE GOT A 3683 03:14:55,775 --> 03:14:58,277 GREAT AFTERNOON LINEUP. 3684 03:14:58,277 --> 03:14:59,245 I HOPE YOU CAN STICK THROUGH IT 3685 03:14:59,245 --> 03:15:00,346 FOR THE WHOLE TIME. 3686 03:15:00,346 --> 03:15:03,082 WE'LL START WITH A TALK FROM 3687 03:15:03,082 --> 03:15:05,718 ARDEM PATAPOUTIAN FROM SCRIPPS 3688 03:15:05,718 --> 03:15:11,624 RESEARCH ON THE ROLE RF PIEZ02 3689 03:15:11,624 --> 03:15:16,462 IN ENTEROSEPTION, THEN WE'LL -- 3690 03:15:16,462 --> 03:15:21,901 ENTER ON ACCEPTING -- ON 3691 03:15:21,901 --> 03:15:23,136 INTEROCEPTION THEN WE'LL HERE 3692 03:15:23,136 --> 03:15:24,871 FROM JULIA PILITSIS, THEN WE'LL 3693 03:15:24,871 --> 03:15:30,476 HEAR FROM JOHN OSBORN, AND THEN 3694 03:15:30,476 --> 03:15:33,079 HEAR FROM RUI CHANG ABOUT THE 3695 03:15:33,079 --> 03:15:37,183 CODING LOGIC OF ENTEROSEPTION IN 3696 03:15:37,183 --> 03:15:41,754 THE VAGUS NERVE, THEN HEAR FROM 3697 03:15:41,754 --> 03:15:45,691 RICHARD LANG WHO WILL TALK ABOUT 3698 03:15:45,691 --> 03:15:47,994 EXTRAOCULAR LIGHT SENSING WI 3699 03:15:47,994 --> 03:15:52,598 ATHE OPSIN GPCR'S R HOPEFULLY 3700 03:15:52,598 --> 03:15:53,900 TIME AFTER FOR ONE QUESTION AND 3701 03:15:53,900 --> 03:15:54,834 REMEMBER YOUR QUESTIONS BECAUSE 3702 03:15:54,834 --> 03:15:56,969 WE'LL HAVE A Q & A AT THE END. 3703 03:15:56,969 --> 03:16:06,913 WE'LL START BY ASKING ARDEM TO 3704 03:16:06,913 --> 03:16:13,519 PRESENT. 3705 03:16:13,519 --> 03:16:15,922 >> HI, EVERYBODY. 3706 03:16:15,922 --> 03:16:17,790 WILL FIRST, I SHOULD START BY 3707 03:16:17,790 --> 03:16:23,563 SAYING THAT I DID NOT APPRECIATE 3708 03:16:23,563 --> 03:16:27,967 ARE KAY TYE TALKING ABOUT THE 3709 03:16:27,967 --> 03:16:29,468 FORMAL ASSAY BECAUSE I FELT LIKE 3710 03:16:29,468 --> 03:16:33,873 I WAS THAT MOUSE ON THE PLEX 3711 03:16:33,873 --> 03:16:35,074 PLEXIGLASS SIDE WATCHING YOU 3712 03:16:35,074 --> 03:16:37,243 GUYS CONSUME SCIENTIFIC 3713 03:16:37,243 --> 03:16:37,643 MILKSHAKE. 3714 03:16:37,643 --> 03:16:39,245 I'M HAPPY TO BE VIRTUAL WITH YOU 3715 03:16:39,245 --> 03:16:43,416 TODAY TO TALK ABOUT WORK WITH 3716 03:16:43,416 --> 03:16:46,152 ION CHANNEL PIEZ02 AND ENTER OH 3717 03:16:46,152 --> 03:16:47,353 SPTION. 3718 03:16:47,353 --> 03:16:49,322 14 YEARS AGO BY LAB IDENTIFIED 3719 03:16:49,322 --> 03:16:56,863 THE CHANNELS CALLS PIEZ02 AND PI 3720 03:16:56,863 --> 03:16:58,164 EZO1, THIS IS THE STRUCTURE OF 3721 03:16:58,164 --> 03:17:02,935 THE TRIEMER, EACH PROTOMER HAS 3722 03:17:02,935 --> 03:17:04,971 38 TRANSMEMBRANE, MORE 3723 03:17:04,971 --> 03:17:06,205 TRANSMEMBRANE DOMAINS THAN ANY 3724 03:17:06,205 --> 03:17:07,607 OTHER PROTEIN IN THE GENOME, ON 3725 03:17:07,607 --> 03:17:09,475 TOP OF IT, THEY COME TOGETHER AS 3726 03:17:09,475 --> 03:17:12,678 A TRIMER FORMING THIS ALMOST 3727 03:17:12,678 --> 03:17:16,515 MILLION DALTON MASSIVE MEMBRANE 3728 03:17:16,515 --> 03:17:17,617 PROTEIN ION CHANNEL AT THE 3729 03:17:17,617 --> 03:17:22,755 PLASMA MEMBRANE AND THIS IS WORK 3730 03:17:22,755 --> 03:17:33,299 BY ASDO -- S AOTOME AND OTHERS. 3731 03:17:37,803 --> 03:17:40,039 FLATTENING AND ALLOWING CATIONS 3732 03:17:40,039 --> 03:17:42,975 INTO THE CELL INITIATING AN 3733 03:17:42,975 --> 03:17:43,943 ACTION POTENTIAL FOR EXAMPLE IN 3734 03:17:43,943 --> 03:17:44,944 SENSORY NEURONS. 3735 03:17:44,944 --> 03:17:46,712 SO OVER THE YEARS, WE'VE DONE A 3736 03:17:46,712 --> 03:17:48,681 VARIETY OF THESE MOUSE GENETICS 3737 03:17:48,681 --> 03:17:51,083 TO FIND WHAT THE ROLES OF THESE 3738 03:17:51,083 --> 03:17:56,589 ION CHANNELS ARE R PIEZ02 IS 3739 03:17:56,589 --> 03:17:59,392 STROJLY EXPRESSED IN THESE THAT 3740 03:17:59,392 --> 03:18:02,261 HELP US SENSE SENSATION, AND IN 3741 03:18:02,261 --> 03:18:04,630 THIS ASSAY YOU CAN SEE, FOR 3742 03:18:04,630 --> 03:18:07,700 EXAMPLE, IN A CERTAIN PIEZ02 3743 03:18:07,700 --> 03:18:10,002 KNOCK-OUT THEY HAVE SEVERE 3744 03:18:10,002 --> 03:18:11,337 UNCOORDINATION, A SIGN OF LACK 3745 03:18:11,337 --> 03:18:13,639 OF APPROXIMATE PROPRIOCEPTION 3746 03:18:13,639 --> 03:18:16,042 AND BELOW YOU CAN SEE WE THINK 3747 03:18:16,042 --> 03:18:20,680 THIS IS DIRECT THE CR MECHANO 3748 03:18:20,680 --> 03:18:22,081 TRANSDUCTION, BECAUSE IF YOU GET 3749 03:18:22,081 --> 03:18:24,250 RIZ OF PIEZ02 THE STRETCH 3750 03:18:24,250 --> 03:18:26,152 ACTIVATED NEURONAL ACTIVITY AT 3751 03:18:26,152 --> 03:18:30,156 THE TERMINI ARE COMPLETELY WIPED 3752 03:18:30,156 --> 03:18:32,024 OUT, ALMOST COMPLETELY WIPED OUT 3753 03:18:32,024 --> 03:18:35,294 IN SEVEN OUT OF EIGHT TRIES THAT 3754 03:18:35,294 --> 03:18:38,064 OUR COLLABORATOR TRIED. 3755 03:18:38,064 --> 03:18:39,899 ONE OF THE INCREDIBLE RESULTS 3756 03:18:39,899 --> 03:18:43,069 ACTUALLY CAME NOT FROM OUR LAB 3757 03:18:43,069 --> 03:18:45,371 BUT ALEX SCHLOESSER'S LAB THERE 3758 03:18:45,371 --> 03:18:47,573 AT THE NIH AND THEY ACTUALLY 3759 03:18:47,573 --> 03:18:49,408 IDENTIFIED INDIVIDUALS WHO ARE 3760 03:18:49,408 --> 03:18:53,479 LOSS OF FUNCTION OF PIEZ02 IN 3761 03:18:53,479 --> 03:18:55,881 HUMANS, THIS IS COMPLETE NULL 3762 03:18:55,881 --> 03:18:59,485 MUTATIONS AND THEY RECAPITULATED 3763 03:18:59,485 --> 03:19:01,253 MANY OF THE SOMATOSENSORY TYPES 3764 03:19:01,253 --> 03:19:02,355 WE OBSERVED IN THE MICE, 3765 03:19:02,355 --> 03:19:04,323 INCLUDING LACK OF TYPE AND 3766 03:19:04,323 --> 03:19:05,291 PROPRIOCEPTION AND THIS VIDEO 3767 03:19:05,291 --> 03:19:08,127 WILL SHOW THIS INDIVIDUAL WHO IS 3768 03:19:08,127 --> 03:19:11,564 A PIEZ02 NULL, SHE'S HARNESSED 3769 03:19:11,564 --> 03:19:13,933 FOR HER OWN PROTECTION, 3770 03:19:13,933 --> 03:19:14,834 BLINDFOLD AND HAD SIMPLY ASKED 3771 03:19:14,834 --> 03:19:16,335 TO WALK IN A STRAIGHT LINE, AND 3772 03:19:16,335 --> 03:19:17,436 SOMETHING THAT MOST OF US WILL 3773 03:19:17,436 --> 03:19:18,804 HAVE A VERY EASY TIME, AS YOU 3774 03:19:18,804 --> 03:19:20,840 CAN SEE, SHE STRUGGLES WITH 3775 03:19:20,840 --> 03:19:22,141 THIS, AGAIN, THIS LACK OF 3776 03:19:22,141 --> 03:19:24,777 COORDINATION IS A SIGN FOR LACK 3777 03:19:24,777 --> 03:19:25,878 OF PROPRIOCEPTION. 3778 03:19:25,878 --> 03:19:27,813 SO I'LL JUST SUMMARIZE ABOUT 3779 03:19:27,813 --> 03:19:30,249 OVER TEN YEARS OF WORK IN THIS 3780 03:19:30,249 --> 03:19:30,549 SLIDE. 3781 03:19:30,549 --> 03:19:32,985 THIS AND MANY OTHER STUDIES TOLD 3782 03:19:32,985 --> 03:19:38,758 US THAT POSE 2 MAINLY -- THAT 3783 03:19:38,758 --> 03:19:40,826 PIEZ02 IS MAINLY RESPONSIBLE FOR 3784 03:19:40,826 --> 03:19:43,829 SENSE OF TOUCH, PROPRIOCEPTION, 3785 03:19:43,829 --> 03:19:45,798 ALSO CLINICALLY IMPORTANT 3786 03:19:45,798 --> 03:19:49,735 TACTILE ALLODYN I A WHEN TOUCH 3787 03:19:49,735 --> 03:19:51,037 BECOMES PAINFUL, AS WELL AS 3788 03:19:51,037 --> 03:20:01,580 MECHANICAL ITCH, BY PIES RPIEZO1 3789 03:20:02,181 --> 03:20:06,485 AND ARE SCRATCHY SWEATER OR BUGS 3790 03:20:06,485 --> 03:20:09,221 FEELING LIKE CRAWLING ON YOUR 3791 03:20:09,221 --> 03:20:10,856 SKIN. 3792 03:20:10,856 --> 03:20:13,259 WE GOT ENTERED IN WITH THIS IDEA 3793 03:20:13,259 --> 03:20:15,661 THERE'S LOTS OF WORK ALREADY 3794 03:20:15,661 --> 03:20:18,831 DONE THAT NODOSE GANGLION 3795 03:20:18,831 --> 03:20:20,800 INNERVATES MANY OF THE INTERNAL 3796 03:20:20,800 --> 03:20:27,807 ORG ORGANS, BUT NOT ONLY WERE 3797 03:20:27,807 --> 03:20:29,542 SENSORS NOT KNOWN, IN MANY OF 3798 03:20:29,542 --> 03:20:32,411 THESE CASES, WHAT IS THE ROLE OF 3799 03:20:32,411 --> 03:20:33,813 MECHANO TRANSDUCTION IN SENSING 3800 03:20:33,813 --> 03:20:36,348 THESE INTERNAL ORGANS WAS 3801 03:20:36,348 --> 03:20:38,417 UNKNOWN, SO A VARIETY OF 3802 03:20:38,417 --> 03:20:41,720 COLLABORATIONS WITH ADAM 3803 03:20:41,720 --> 03:20:43,022 SCHLOESSER'S LAB, WE HAVE SHOWN 3804 03:20:43,022 --> 03:20:45,291 FOR EXAMPLE THAT BOTH IN MICE 3805 03:20:45,291 --> 03:20:47,293 AND HUMANS ARE PIEZ02 IS 3806 03:20:47,293 --> 03:20:50,129 REQUIRED FOR LONG STRETCH, 3807 03:20:50,129 --> 03:20:52,231 REFLEX AND ACTUALLY IN 3808 03:20:52,231 --> 03:20:53,866 INDIVIDUALS WITHOUT PIEZ02 HAVE 3809 03:20:53,866 --> 03:20:55,601 MASSIVE RESPIRATION PROBLEMS 3810 03:20:55,601 --> 03:20:57,369 RIGHT AFTER BIRTH AND ARE 3811 03:20:57,369 --> 03:20:58,904 HOSPITALIZED FOR THIS, THERE ARE 3812 03:20:58,904 --> 03:21:01,340 MANY WAYS TO SENSE AND CONTROL 3813 03:21:01,340 --> 03:21:03,075 BLOOD PRESSURE, THE NEURONAL 3814 03:21:03,075 --> 03:21:04,910 SENSORY MECHANISM TO THE VAGUS 3815 03:21:04,910 --> 03:21:06,579 IS CALLED BEARER RECEPTION AND 3816 03:21:06,579 --> 03:21:11,217 WE'VE SHOWN THAT BOTH PIEZO1 AND 3817 03:21:11,217 --> 03:21:13,119 2 IN THIS CASE ARE REQUIRED FOR 3818 03:21:13,119 --> 03:21:15,421 THE SENSE OF BETTER RECEPTION. 3819 03:21:15,421 --> 03:21:16,655 MARSHALL WAS AN ALUMENT NUS P 3820 03:21:16,655 --> 03:21:19,692 FROM THE LAB -- ALUM NUPS FROM 3821 03:21:19,692 --> 03:21:21,994 THE LAB EXRRKS RUNS LAB AT 3822 03:21:21,994 --> 03:21:23,329 BAYLOR ARE COLLEGE OF MEDICINE, 3823 03:21:23,329 --> 03:21:24,763 ALSO IN THE AUDIENCE TODAY, 3824 03:21:24,763 --> 03:21:27,166 SHOWS BLADDER STRETCH, THIS 3825 03:21:27,166 --> 03:21:28,701 SENSE THAT TELLS YOU WHEN YOU 3826 03:21:28,701 --> 03:21:30,336 NEED TO GO TO THE RESTROOM BOTH 3827 03:21:30,336 --> 03:21:33,405 IN MICE AND IN HUMANS ONCE AGAIN 3828 03:21:33,405 --> 03:21:36,375 DEPENDS ON PIEZ02, THESE 3829 03:21:36,375 --> 03:21:37,343 INDIVIDUALS WITHOUT PIEZ02 THEY 3830 03:21:37,343 --> 03:21:38,644 LEARN AS THEY GROW UP THAT 3831 03:21:38,644 --> 03:21:39,745 THEY'RE NOT GETTING THIS 3832 03:21:39,745 --> 03:21:41,180 SENSATION, SO THEY GO TO THE 3833 03:21:41,180 --> 03:21:43,249 RESTROOM TO A SCHOOL TWO TO 3834 03:21:43,249 --> 03:21:46,218 THREE TIMES A DAY TO AVOID 3835 03:21:46,218 --> 03:21:46,485 ACCIDENTS. 3836 03:21:46,485 --> 03:21:50,022 IN ADDITION, WE JUST RECENTLY 3837 03:21:50,022 --> 03:21:51,557 PUBLISHED THERE IN THE LAB THAT 3838 03:21:51,557 --> 03:21:54,727 AGAIN BOTH IN MOUSE AND HEUMANN 3839 03:21:54,727 --> 03:21:58,230 GULT MOTILITY IS REGULATED VIA 3840 03:21:58,230 --> 03:21:59,098 POSE PIEZ02. 3841 03:21:59,098 --> 03:22:00,966 SO ALL OF THIS IS GREAT, BUT 3842 03:22:00,966 --> 03:22:02,268 WHAT I WANT TO TALK ABOUT NOW 3843 03:22:02,268 --> 03:22:03,903 AND WHAT THE LAB IS REALLY 3844 03:22:03,903 --> 03:22:07,239 FOCUSING IS I CALL PHASE 26 3845 03:22:07,239 --> 03:22:09,975 STUDYING PIEZO'S IN 3846 03:22:09,975 --> 03:22:10,509 INTEROCEPTION, THAT IS 3847 03:22:10,509 --> 03:22:11,710 EVERYTHING I DESCRIBED TO YOU 3848 03:22:11,710 --> 03:22:13,679 BEFORE WAS KIND OF KNOWN THAT 3849 03:22:13,679 --> 03:22:13,913 HAPPENS. 3850 03:22:13,913 --> 03:22:15,581 WHAT I MEAN BY THAT IS WE KNEW 3851 03:22:15,581 --> 03:22:16,649 THAT YOUR BLADDER STRETCHES 3852 03:22:16,649 --> 03:22:18,417 EXPUF GET A SENSATION FROM -- 3853 03:22:18,417 --> 03:22:20,252 AND YOU GET A SENSATION FROM IT, 3854 03:22:20,252 --> 03:22:21,887 SAME WITH LUNG AND 3855 03:22:21,887 --> 03:22:22,755 PROPRIOCEPTION AND PAIN. 3856 03:22:22,755 --> 03:22:26,158 BUT WE ALSO KNOW THAT THE INT 3857 03:22:26,158 --> 03:22:29,862 ERS RG HE ONS ALSO INNERVATE 3858 03:22:29,862 --> 03:22:31,430 PANCREAS, ADIPOSE, KIDNEY, I CAN 3859 03:22:31,430 --> 03:22:33,032 LIST TEN MORE AND THE ROLE OF 3860 03:22:33,032 --> 03:22:35,134 THE SENSORY NEURONS AS WELL AS 3861 03:22:35,134 --> 03:22:37,002 MECHANOSENSATION IS REALLY NOT 3862 03:22:37,002 --> 03:22:40,472 WELL UNDERSTOOD. 3863 03:22:40,472 --> 03:22:44,109 AND YU WANG A GRADUATE STUDENT 3864 03:22:44,109 --> 03:22:48,480 IN THE LAB SHOWED WITH LI YE 3865 03:22:48,480 --> 03:22:49,682 ALSO AT SCRIPPS WANTED TO TACKLE 3866 03:22:49,682 --> 03:22:52,651 THIS PROBLEM, FOCUSED ON ADIPOSE 3867 03:22:52,651 --> 03:22:52,952 TISSUE. 3868 03:22:52,952 --> 03:22:54,720 THE TEXTBOOK VERSION OF HOW 3869 03:22:54,720 --> 03:22:56,255 ADIPOSE TISSUE COMMUNICATES WITH 3870 03:22:56,255 --> 03:22:59,858 THE BRAIN IS THAT THEY IS HE 3871 03:22:59,858 --> 03:23:04,263 SECRETE HORMONES, LEPTIN AND 3872 03:23:04,263 --> 03:23:06,432 THESE HORMONES GO TO THE BRAIN 3873 03:23:06,432 --> 03:23:09,501 AND ASSESS YOUR WHOLE M 3874 03:23:09,501 --> 03:23:10,603 METABOLIC CONDITION AND THROUGH 3875 03:23:10,603 --> 03:23:12,371 THE MOTOR SYMPATHETIC NERVOUS 3876 03:23:12,371 --> 03:23:15,541 SYSTEM REGULATES ADIPOGENESIS, 3877 03:23:15,541 --> 03:23:17,509 THERMOGENESIS, ET CETERA. 3878 03:23:17,509 --> 03:23:19,578 HOWEVER, THERE WERE ANECDOTAL 3879 03:23:19,578 --> 03:23:21,213 INFORMATION THAT THE SENSORY 3880 03:23:21,213 --> 03:23:23,849 NEURONS ALSO INNERVATING THE FAT 3881 03:23:23,849 --> 03:23:26,585 PAD AND YI WANTED TO FIND OUT 3882 03:23:26,585 --> 03:23:30,189 WHAT DO THESE NEURONS DO. 3883 03:23:30,189 --> 03:23:31,724 SHE FIRST LOOKED AND SHOWED THAT 3884 03:23:31,724 --> 03:23:34,360 THERE IS ROBUST DRG INNERVATION 3885 03:23:34,360 --> 03:23:36,428 OF FAT THAT I'M SHOWING YOU, BUT 3886 03:23:36,428 --> 03:23:38,831 TO LOOK AT THE FUNCTION, SHE 3887 03:23:38,831 --> 03:23:41,267 FOCUSED ON THIS INGUINAL WHITE 3888 03:23:41,267 --> 03:23:43,335 ADIPOSE TISSUE THAT ALSO HAS 3889 03:23:43,335 --> 03:23:45,304 ESPECIALLY WHEN INDUCED BY 3890 03:23:45,304 --> 03:23:47,706 STRESSES SUCH AS COLD HAS BROWN 3891 03:23:47,706 --> 03:23:49,908 ADIPOSE TISSUE, THERMOGENIC 3892 03:23:49,908 --> 03:23:51,043 PROPERTIES AS WELL, AND SHE HAD 3893 03:23:51,043 --> 03:23:52,511 TO DO LOTS OF NEW TECHNOLOGY 3894 03:23:52,511 --> 03:23:54,280 DEVELOPMENT TO BE ABLE TO DO 3895 03:23:54,280 --> 03:23:56,682 THESE STUDIES, INCLUDING 3896 03:23:56,682 --> 03:23:59,385 EVOLVING NEW AAV VIRUSES THAT 3897 03:23:59,385 --> 03:24:03,122 SHE COULD DELIVER, IT CREATE THE 3898 03:24:03,122 --> 03:24:04,623 ADIPOSE TISSUE FOR EXAMPLE. 3899 03:24:04,623 --> 03:24:06,959 SHE MENTIONED DUAL SYSTEM, CRE 3900 03:24:06,959 --> 03:24:11,664 COMES IN FROM AEV BEING INJECTED 3901 03:24:11,664 --> 03:24:13,866 INTO THE FAT PAD. 3902 03:24:13,866 --> 03:24:17,770 IN MICE INFECTED WITH AEV 3903 03:24:17,770 --> 03:24:19,004 PREINDEPENDENT IF TOXIN 3904 03:24:19,004 --> 03:24:21,206 EXPRESSING SO THIS IN THIS CASE 3905 03:24:21,206 --> 03:24:24,376 ONLY DRG NEURONS THAT INNERVATE 3906 03:24:24,376 --> 03:24:26,645 THIS FATALITY PAD WOULD BE 3907 03:24:26,645 --> 03:24:27,212 ABLATED. 3908 03:24:27,212 --> 03:24:28,280 SYMPATHETIC NERVOUS SYSTEM WOULD 3909 03:24:28,280 --> 03:24:30,716 BE NORMAL AND DRG INNERVATING 3910 03:24:30,716 --> 03:24:32,117 OTHER TISSUES WOULD BE NORMAL. 3911 03:24:32,117 --> 03:24:33,786 WHEN SHE DID THIS, REMARKABLY 3912 03:24:33,786 --> 03:24:36,055 SHE SAW A VERY STRONG PHENOTYPE, 3913 03:24:36,055 --> 03:24:38,257 AS YOU CAN SEE HERE, THERE'S 3914 03:24:38,257 --> 03:24:42,027 MASSIVE EN RIDGEMENT RF ADIPOSE 3915 03:24:42,027 --> 03:24:44,963 SITES AS WELL AS UPREGULATION, 3916 03:24:44,963 --> 03:24:48,367 RNA SEC FROM FAT PADS FROM 3917 03:24:48,367 --> 03:24:50,336 ABLATED VERSUS CONTROL ANIMALS, 3918 03:24:50,336 --> 03:24:53,939 RNA SEQ SUGGEST THAT HAD 3919 03:24:53,939 --> 03:24:54,807 UPREGULATION IN MANY OF THE 3920 03:24:54,807 --> 03:24:55,974 TYPES OF GENES THAT WE KNOW 3921 03:24:55,974 --> 03:24:58,277 WOULD BE ALSO UPREGULATED IF YOU 3922 03:24:58,277 --> 03:25:00,379 ACTIVATE THE SYMPATHETIC NERVOUS 3923 03:25:00,379 --> 03:25:00,679 SYSTEM. 3924 03:25:00,679 --> 03:25:02,881 SO THE CONCLUSION HERE IS THAT 3925 03:25:02,881 --> 03:25:06,185 IT SEEMS LIKE ABLATING THE DRG 3926 03:25:06,185 --> 03:25:07,820 NEURONS IS EQUIVALENT OF 3927 03:25:07,820 --> 03:25:09,688 ACTIVATION OF THE SYMPATHETIC, 3928 03:25:09,688 --> 03:25:11,223 SO IT'S ALMOST A NEGATIVE 3929 03:25:11,223 --> 03:25:12,858 FEEDBACK LOOP, LIKE MANY OTHER 3930 03:25:12,858 --> 03:25:14,593 SENSORY SYSTEMS, INCLUDING THE 3931 03:25:14,593 --> 03:25:16,795 BEARER RECEPTOR SYSTEM OF THE 3932 03:25:16,795 --> 03:25:18,530 BUT THE QUESTION WAS, WHAT ARE 3933 03:25:18,530 --> 03:25:19,832 THE SENSORY NEURONS ACTUALLY 3934 03:25:19,832 --> 03:25:21,433 SENSING IN THE FAT PAD? 3935 03:25:21,433 --> 03:25:22,835 INITIALLY WE THOUGHT IT MIGHT BE 3936 03:25:22,835 --> 03:25:26,238 MANY THINGS, BUT PROBABLY NOT 3937 03:25:26,238 --> 03:25:26,638 MECHANOSENSATION. 3938 03:25:26,638 --> 03:25:28,507 SO THE REST OF THE WORK IS 3939 03:25:28,507 --> 03:25:32,578 UNPUBLISHED WORK FROM YI'S 3940 03:25:32,578 --> 03:25:32,811 THESIS. 3941 03:25:32,811 --> 03:25:38,717 SO FIRST SHE WANTED TO SEE IF 3942 03:25:38,717 --> 03:25:43,021 PIEZ02 FIBERS -- PIES POSITIVE 3943 03:25:43,021 --> 03:25:45,190 FIBERS WERE EXPRESSED IN FAT 3944 03:25:45,190 --> 03:25:45,624 PAD. 3945 03:25:45,624 --> 03:25:49,361 SHE SHE TAKES AN AAV THAT'S 3946 03:25:49,361 --> 03:25:52,631 FLOXED, SO CRE-DEPENDENT 3947 03:25:52,631 --> 03:25:53,499 FLUORESCENT MARKER EXPRESSING 3948 03:25:53,499 --> 03:25:56,769 AND DOES THIS IN A PIEZ02 CRE 3949 03:25:56,769 --> 03:25:58,871 MICE SO WHEN SHE INJECTS DRG SHE 3950 03:25:58,871 --> 03:26:01,140 CAN WATCH THE NEURONS EXPRESSING 3951 03:26:01,140 --> 03:26:02,574 PIEZ02 ALL THE WAY INTO THE FAD 3952 03:26:02,574 --> 03:26:05,411 PAT SO THIS IS A CLEARED AND 3953 03:26:05,411 --> 03:26:08,180 LIGHT SHEET MIE CROSS MICROSCOPY 3954 03:26:08,180 --> 03:26:10,149 IMAGE OF WHAT WE LOOK AT AND 3955 03:26:10,149 --> 03:26:12,885 THERE'S MASSIVE INNERVATION OF 3956 03:26:12,885 --> 03:26:14,853 PIEZ02 POSITIVE NEURONS. 3957 03:26:14,853 --> 03:26:16,588 SO IF YOU LOOK CLOSELY AT THIS 3958 03:26:16,588 --> 03:26:18,891 YOU CAN SEE THAT SOME OF THESE 3959 03:26:18,891 --> 03:26:20,526 NEURONS ARE WRAPPED AROUND BLOOD 3960 03:26:20,526 --> 03:26:21,960 VESSELS WITHIN THE FAT, SOME 3961 03:26:21,960 --> 03:26:26,999 COME VERY CLOSE TO THE ACTUALLY 3962 03:26:26,999 --> 03:26:28,767 ADIPOSE SITES, SO IN CLOSE 3963 03:26:28,767 --> 03:26:29,868 PROXIMITY TO THEM. 3964 03:26:29,868 --> 03:26:32,171 I'M SHOWING YOU, BUT SHE ALSO 3965 03:26:32,171 --> 03:26:33,806 DID RETROGRADE TRACING SHOWING 3966 03:26:33,806 --> 03:26:36,875 THAT HALF OF FAT-INNERVATING 3967 03:26:36,875 --> 03:26:38,177 NEURONS EXPRESS PIEZ02. 3968 03:26:38,177 --> 03:26:39,144 AGAIN, THIS IS REMARKABLE 3969 03:26:39,144 --> 03:26:40,379 BECAUSE THIS IS ALMOST THE SAME 3970 03:26:40,379 --> 03:26:43,515 NUMBER WE GET IF WE LOOK AT SKIN 3971 03:26:43,515 --> 03:26:43,882 CELLS. 3972 03:26:43,882 --> 03:26:45,284 SKIN TISSUE WHICH HAS BEEN 3973 03:26:45,284 --> 03:26:47,352 STUDIED FOR DECADES HAS THE SAME 3974 03:26:47,352 --> 03:26:49,321 AMOUNT OF PIEZ02 INNERVATING 3975 03:26:49,321 --> 03:26:50,856 NEURONS AND YET NOTHING IS KNOWN 3976 03:26:50,856 --> 03:26:54,059 ABOUT THESE NEURONS INNERVATING 3977 03:26:54,059 --> 03:26:54,893 THE FAT PAD. 3978 03:26:54,893 --> 03:26:56,862 IF YOU LOOK AT THE FUNCTION OF 3979 03:26:56,862 --> 03:27:00,399 THESE NEURONS, NOW, INSTEAD OF 3980 03:27:00,399 --> 03:27:02,334 ABLATING NEURONS, WE'RE SIMPLY 3981 03:27:02,334 --> 03:27:05,170 DELETING PIEZ02 FROM DRGS 3982 03:27:05,170 --> 03:27:06,271 INNERVATING FAT PAD AND IN THIS 3983 03:27:06,271 --> 03:27:07,940 CASE YOU DID INTERNAL CONTROL. 3984 03:27:07,940 --> 03:27:10,542 SO ONE SIDE, SHE'S INJECTING CRE 3985 03:27:10,542 --> 03:27:12,311 IN THE FAT PAD OF ONE SIDE AND 3986 03:27:12,311 --> 03:27:13,846 CONTROL IN THE OTHER, IN PIEZ02 3987 03:27:13,846 --> 03:27:15,814 LOSS OF FUNCTION ANIMAL, SO ONLY 3988 03:27:15,814 --> 03:27:18,116 THE DRG NEURONS EXPRESSING 3989 03:27:18,116 --> 03:27:19,651 PIEZ02 WILL DELETE THE ONES THAT 3990 03:27:19,651 --> 03:27:21,520 ARE INNERVATING THE FAT PAD 3991 03:27:21,520 --> 03:27:21,753 ITSELF. 3992 03:27:21,753 --> 03:27:23,388 WHEN SHE TAKES THE FAT PADS 3993 03:27:23,388 --> 03:27:25,757 AFTERWARDS AND DOES RNA SEQ, 3994 03:27:25,757 --> 03:27:26,992 REMARKABLY SHE SEES ALL THE 3995 03:27:26,992 --> 03:27:30,929 GENES THAT WERE UPREGULATED FOR 3996 03:27:30,929 --> 03:27:33,665 ABLATION OF DRG'S INNERVATING 3997 03:27:33,665 --> 03:27:35,601 THE FAT PAD ARE AGAIN COMING UP. 3998 03:27:35,601 --> 03:27:36,668 THIS IS QUITE STRIKELY. 3999 03:27:36,668 --> 03:27:38,270 IF I SHOW YOU THIS PLOT WHERE 4000 03:27:38,270 --> 03:27:39,938 WE'RE COMPARING THE GENES 4001 03:27:39,938 --> 03:27:41,573 UPREGULATED IN DRG ABLATION ON 4002 03:27:41,573 --> 03:27:43,442 THE X AXIS COMPARED TO LOSS OF 4003 03:27:43,442 --> 03:27:45,511 FUNCTION OF PIEZ02 ONLY, YOU CAN 4004 03:27:45,511 --> 03:27:48,046 SEE THERE'S A VERY NICE POSITIVE 4005 03:27:48,046 --> 03:27:48,347 CORRELATION. 4006 03:27:48,347 --> 03:27:53,719 SO IT SEEMS LIKE NOTHING BUT 4007 03:27:53,719 --> 03:27:56,588 PIEZ02 CAN RECAPITULATE THE PR 4008 03:27:56,588 --> 03:28:01,393 PHENOTYPE OF COMPLEES DRG THERE 4009 03:28:01,393 --> 03:28:01,693 REGULATION. 4010 03:28:01,693 --> 03:28:02,828 CR DOES THIS IN THE PRESENCE OF 4011 03:28:02,828 --> 03:28:04,463 HIGH FAT DIET AND COME BACK TO 4012 03:28:04,463 --> 03:28:04,696 THIS. 4013 03:28:04,696 --> 03:28:06,331 WHEN YOU GET A SURPRISING RUMENT 4014 03:28:06,331 --> 03:28:08,700 LIKE THIS, WHICH IS PIEZ02 4015 03:28:08,700 --> 03:28:10,035 SENSING SOMETHING MECHANICAL IN 4016 03:28:10,035 --> 03:28:11,570 FAT PAD IT'S VERY NICE TO GET 4017 03:28:11,570 --> 03:28:12,471 GENETIC EVIDENCE FROM ANOTHER 4018 03:28:12,471 --> 03:28:15,541 TYPE OF STUDY AND GENETICISTS 4019 03:28:15,541 --> 03:28:17,643 LOVE TO LOOK AT BOTH GAIN OF 4020 03:28:17,643 --> 03:28:18,644 FUNCTION AND LOSS OF FUNCTION 4021 03:28:18,644 --> 03:28:20,712 AND SINCE WE HAVE CONFIRMED GAIN 4022 03:28:20,712 --> 03:28:22,247 OF FUNCTION MICE WITH PIEZ02 4023 03:28:22,247 --> 03:28:24,116 SAID WHAT HAPPENS IF WE DID THE 4024 03:28:24,116 --> 03:28:25,217 SAME EXPERIMENT WITH THESE GAIN 4025 03:28:25,217 --> 03:28:26,351 OF FUNCTION ANIMALS. 4026 03:28:26,351 --> 03:28:28,587 SAME TYPE OF ERNS SPEMPLET, CRE 4027 03:28:28,587 --> 03:28:29,922 ON ONE SIDE, CONTROL ON THE 4028 03:28:29,922 --> 03:28:31,156 OTHER, BY GAIN OF FUNCTION I 4029 03:28:31,156 --> 03:28:33,559 MEAN THIS IS A GENE STILL 4030 03:28:33,559 --> 03:28:35,961 MECHANICALLY ACTIVATED BUT MORE 4031 03:28:35,961 --> 03:28:39,031 SLOWLY INACTIVATING SO YOU GET A 4032 03:28:39,031 --> 03:28:40,899 CERTAIN AMOUNT OF STIMULUS. 4033 03:28:40,899 --> 03:28:43,602 DID THIS IN RNA SEQ ON FAT PAD 4034 03:28:43,602 --> 03:28:44,770 SHE DIDN'T SEE ANYTHING. 4035 03:28:44,770 --> 03:28:47,005 BUT YU ALWAYS HAS A BACKUP AND 4036 03:28:47,005 --> 03:28:48,073 HAD ALSO DONE THESE EXPERIMENTS 4037 03:28:48,073 --> 03:28:49,641 IN THE PRESENCE OF HIGH FAT 4038 03:28:49,641 --> 03:28:51,476 DIET, AND HIGH FAT DIET WE 4039 03:28:51,476 --> 03:28:53,545 THOUGHT WAS IMPORTANT BECAUSE 4040 03:28:53,545 --> 03:28:54,780 THERE'S MORE MECHANICAL 4041 03:28:54,780 --> 03:28:56,848 STIMULATION IN THIS CONDITION. 4042 03:28:56,848 --> 03:28:58,951 SO THE FA PADS GET BIGGER, 4043 03:28:58,951 --> 03:29:01,386 STIFFER DURING HIGH FAT DIET, AS 4044 03:29:01,386 --> 03:29:03,455 LONG AS CELLS EXPAND, THERE'S 4045 03:29:03,455 --> 03:29:07,359 MORE CELLS AND THERE'S VASO 4046 03:29:07,359 --> 03:29:08,460 VASODILATION THAT'S A RELEVANT 4047 03:29:08,460 --> 03:29:08,727 STIMULUS. 4048 03:29:08,727 --> 03:29:10,095 WHEN SHE DID THIS AND COMPARED 4049 03:29:10,095 --> 03:29:12,397 THE TWO SIDES OF THE FAT PADS, 4050 03:29:12,397 --> 03:29:14,600 NOW SHE SAW THAT MANY OF THE 4051 03:29:14,600 --> 03:29:16,668 GENES THAT WERE BEING 4052 03:29:16,668 --> 03:29:18,236 UPREGULATED IN THE KNOCK-OUT OR 4053 03:29:18,236 --> 03:29:19,805 ABLATION NOW ARE DOWN REGULATED 4054 03:29:19,805 --> 03:29:22,708 IN THE CRE POSITIVE SIDE. 4055 03:29:22,708 --> 03:29:25,911 AGAIN I'M SHOANG THE CORRELATIOE 4056 03:29:25,911 --> 03:29:27,346 LAKES OF THE GAIN OF FUNCTION 4057 03:29:27,346 --> 03:29:28,847 VERSUS LOSS OF FUNCTION IN HIGH 4058 03:29:28,847 --> 03:29:32,317 FAT DIET, NOW YOU SEE VERY 4059 03:29:32,317 --> 03:29:36,288 STRIKING NEGATIVE CORRELATIONS. 4060 03:29:36,288 --> 03:29:39,024 SO IN SUMMARY, FAT HAS FEELINGS 4061 03:29:39,024 --> 03:29:39,625 TOO. 4062 03:29:39,625 --> 03:29:41,093 INNERVATION OF THE FAT PAD SEEMS 4063 03:29:41,093 --> 03:29:44,396 TO HAVE AN INHIBITORY BREAK ON 4064 03:29:44,396 --> 03:29:46,565 THE SYMPATHETIC SYSTEM. 4065 03:29:46,565 --> 03:29:48,300 SURPRISINGLY, WE FIND THAT 4066 03:29:48,300 --> 03:29:49,601 MECHANOSENSATION IS VERY 4067 03:29:49,601 --> 03:29:52,671 CRITICAL FOR THIS PROCESS. 4068 03:29:52,671 --> 03:29:55,974 WE'RE VERY INTERESTED IN WHAT 4069 03:29:55,974 --> 03:29:57,609 MECHANICAL FORCES ARE AT PLAY IN 4070 03:29:57,609 --> 03:29:57,776 FAT. 4071 03:29:57,776 --> 03:29:58,810 THIS IS VERY DIFFICULT TO 4072 03:29:58,810 --> 03:29:59,044 ANSWER. 4073 03:29:59,044 --> 03:30:02,648 IT'S GOING ON REQUIRE NOVEL 4074 03:30:02,648 --> 03:30:04,182 TECHNOLOGY DEVELOPMENT FOR US TO 4075 03:30:04,182 --> 03:30:07,586 KNOW WHAT'S HAPPENING IN VIVO IN 4076 03:30:07,586 --> 03:30:09,655 FAT PADS IN RESPONSE TO VARIOUS 4077 03:30:09,655 --> 03:30:10,756 CONDITIONS BUT AS I MENTIONED IT 4078 03:30:10,756 --> 03:30:12,057 COULD BE THE STIFFNESS OF THE 4079 03:30:12,057 --> 03:30:13,592 FAT PAD, COULD BE THE ACTUAL 4080 03:30:13,592 --> 03:30:15,127 CELLS ENLARGING AND PUTTING 4081 03:30:15,127 --> 03:30:17,095 PRESSURE ON THE NERVE ENDINGS, 4082 03:30:17,095 --> 03:30:20,165 IT COULD BE VASODILATION. 4083 03:30:20,165 --> 03:30:21,500 BUT FINALLY I THINK THIS IS 4084 03:30:21,500 --> 03:30:23,802 MAINLY A PROOF OF CONCEPT OF THE 4085 03:30:23,802 --> 03:30:25,437 MANY DIFFERENT ROLES IN THE NEXT 4086 03:30:25,437 --> 03:30:28,173 DECADE WE'RE GOING TO FIND OF 4087 03:30:28,173 --> 03:30:29,775 THE SENSORY NERVOUS SYSTEM 4088 03:30:29,775 --> 03:30:31,209 PLAYING IMPORTANT ROLE OF 4089 03:30:31,209 --> 03:30:33,311 REGULATING AND SENSING VARIOUS 4090 03:30:33,311 --> 03:30:36,148 INTERNAL ORGANS. 4091 03:30:36,148 --> 03:30:37,449 SO I WOULD JUST LIKE TO THANK 4092 03:30:37,449 --> 03:30:39,317 FOR MORE OF THE INTRODUCTION 4093 03:30:39,317 --> 03:30:45,657 PART, MANY OF THE -- THEY 4094 03:30:45,657 --> 03:30:48,193 STARTED MANY OF THESE KNOCK-OUT 4095 03:30:48,193 --> 03:30:51,163 STUDIES, I MENTIONED KARA 4096 03:30:51,163 --> 03:30:53,131 MARSHALL WHO IS THERE DID THE 4097 03:30:53,131 --> 03:30:55,000 BLADDER WORK, ROSE HILL DID THE 4098 03:30:55,000 --> 03:30:56,535 ITCH WORK AND ON THE PRACTICES 4099 03:30:56,535 --> 03:30:57,703 WHERE THESE PEOPLE ARE RIGHT NOW 4100 03:30:57,703 --> 03:30:59,805 AND ROSE IS ON THE JOB MARKET 4101 03:30:59,805 --> 03:31:01,206 AND SHE'S FANTASTIC, YOU SHOULD 4102 03:31:01,206 --> 03:31:03,408 LOOK INTO HER, TALK TO HER. 4103 03:31:03,408 --> 03:31:04,810 WE'VE COLLABORATORS THAT I 4104 03:31:04,810 --> 03:31:05,911 MENTIONED AND SOME OF THIS WORK 4105 03:31:05,911 --> 03:31:11,083 AT LEAST WAS FUNDED BY AN 4106 03:31:11,083 --> 03:31:12,050 NINDS NIH R35 MECHANISM WHICH 4107 03:31:12,050 --> 03:31:13,251 I'M VERY GRATEFUL FOR. 4108 03:31:13,251 --> 03:31:15,921 THE WORK ON THE FAT INNERVATION 4109 03:31:15,921 --> 03:31:19,224 IS LED BY YU WANG AS I MENTIONED 4110 03:31:19,224 --> 03:31:22,027 IN A COLLABORATIVE EFFORT WITH Y 4111 03:31:22,027 --> 03:31:24,196 RERKS LAB MY NEIGHBOR AND IN 4112 03:31:24,196 --> 03:31:26,631 THIS WE HAVE A WONDERFUL RO1 4113 03:31:26,631 --> 03:31:28,600 FROM NIH WHICH AGAIN I'M VERY 4114 03:31:28,600 --> 03:31:29,434 GRATEFUL FOR. 4115 03:31:29,434 --> 03:31:36,842 THANKS AGAIN FOR YOUR ATTENTION. 4116 03:31:36,842 --> 03:31:40,312 >> THANK YOU VERY MUCH, ARDEM. 4117 03:31:40,312 --> 03:31:42,314 TIME FOR ONE QUESTION. 4118 03:31:42,314 --> 03:31:43,515 PLEASE IF YOU HAVE A QUESTION, 4119 03:31:43,515 --> 03:31:53,258 STEP UP TO THE MIC. 4120 03:31:53,258 --> 03:31:55,160 >> HI. 4121 03:31:55,160 --> 03:31:56,261 I'M CURIOUS TO KNOW IF YOU THINK 4122 03:31:56,261 --> 03:31:57,729 THAT OTHER CELL TYPES RESIDENT 4123 03:31:57,729 --> 03:32:00,799 IN THE FAT TISSUE LIKE MICROGLIA 4124 03:32:00,799 --> 03:32:05,237 MIGHT BE TUG OG THIS PIEZO 4125 03:32:05,237 --> 03:32:05,470 FIBERS? 4126 03:32:05,470 --> 03:32:06,905 >> ABSOLUTELY. 4127 03:32:06,905 --> 03:32:09,641 I DIDN'T MENTION IT BUT WE ARE 4128 03:32:09,641 --> 03:32:10,609 CONSIDERABLE POTENTIAL IMMUNE 4129 03:32:10,609 --> 03:32:12,911 AND RELATED CELLS BEING POSSIBLY 4130 03:32:12,911 --> 03:32:15,881 THE SOURCE OF THE MECHANICAL 4131 03:32:15,881 --> 03:32:16,214 STIMULATION. 4132 03:32:16,214 --> 03:32:19,484 AS I SAID, I THINK WE WOULD LOVE 4133 03:32:19,484 --> 03:32:22,988 TO HAVE SOME KIND OF SENSOR THAT 4134 03:32:22,988 --> 03:32:24,856 WOULD TELL US IN VIVO DURING 4135 03:32:24,856 --> 03:32:27,359 EITHER NORMAL PHYSIOLOGY OR 4136 03:32:27,359 --> 03:32:29,694 PATHOPHYSIOLOGY WHAT FORCES ARE 4137 03:32:29,694 --> 03:32:33,532 AT PLAY, AND IT'S VERY, VERY 4138 03:32:33,532 --> 03:32:34,399 EXCITING I THINK DIRECTION THAT 4139 03:32:34,399 --> 03:32:36,168 OVER THE NEXT FEW YEARS 4140 03:32:36,168 --> 03:32:37,035 HOPEFULLY WE CAN COLLABORATE AND 4141 03:32:37,035 --> 03:32:40,939 COME UP WITH SOMETHING. 4142 03:32:40,939 --> 03:32:43,208 >> GREAT. 4143 03:32:43,208 --> 03:32:47,479 >> ONE MORE QUICK QUESTION. 4144 03:32:47,479 --> 03:32:49,514 >> ANY IDEA WHAT YOU THINK THE 4145 03:32:49,514 --> 03:32:51,249 NERVE FIBERS AROUND THE BLOOD 4146 03:32:51,249 --> 03:32:52,150 VESSELS ARE DOING? 4147 03:32:52,150 --> 03:32:53,752 THAT'S WHERE THE SIM PA THET IKS 4148 03:32:53,752 --> 03:32:55,754 WOULD BE AS WELL. 4149 03:32:55,754 --> 03:32:57,155 -- SYMPATHETICS WOULD BE AS 4150 03:32:57,155 --> 03:32:57,355 WELL. 4151 03:32:57,355 --> 03:33:00,525 >> YES, SO JUST REMEMBER THAT 4152 03:33:00,525 --> 03:33:03,195 ALL OF YU'S ASSAYS ARE FROM 4153 03:33:03,195 --> 03:33:05,297 DIRECTLY INJECTING THE DRG'S SO 4154 03:33:05,297 --> 03:33:07,899 WE KNOW THESE ARE SOMATOSENSORY 4155 03:33:07,899 --> 03:33:09,768 NEURONS INNERVATING THE BLOOD 4156 03:33:09,768 --> 03:33:10,802 VESSELS, BUT OF COURSE THERE ARE 4157 03:33:10,802 --> 03:33:12,804 SIM PA THETD I CAN AS WELL. 4158 03:33:12,804 --> 03:33:14,239 -- SYMPATHETIC AS WELL. 4159 03:33:14,239 --> 03:33:15,640 IN MANY OF THESE SITUATIONS, FOR 4160 03:33:15,640 --> 03:33:16,875 EXAMPLE, IF YOUR FAT PAD IS 4161 03:33:16,875 --> 03:33:18,310 GOING TO GROARKS YOU'LL NEED 4162 03:33:18,310 --> 03:33:20,912 MORE BLOOD CIRCULATION, AND 4163 03:33:20,912 --> 03:33:22,581 THERE'S GOING TO BE VASODILATION 4164 03:33:22,581 --> 03:33:24,182 AND THIS COULD VERY WELL BE A 4165 03:33:24,182 --> 03:33:27,686 SOURCE OF THE MECHANICAL FORCE 4166 03:33:27,686 --> 03:33:30,088 ACTING IN THE FAT PAD ON THESE 4167 03:33:30,088 --> 03:33:31,990 NERVE ENDINGS. 4168 03:33:31,990 --> 03:33:33,859 WE SEE THIS ACTUALLY IN MANY 4169 03:33:33,859 --> 03:33:35,160 DIFFERENT INTERNAL ORGANS THAT 4170 03:33:35,160 --> 03:33:36,127 WE'RE LOOKING AT. 4171 03:33:36,127 --> 03:33:39,397 THERE'S USUALLY SOME, SOME OF 4172 03:33:39,397 --> 03:33:40,866 THESE SENSORY NERVES ARE ALWAYS 4173 03:33:40,866 --> 03:33:43,435 ASSOCIATED WITH BLOOD VESSELS. 4174 03:33:43,435 --> 03:33:44,603 >> GREAT. 4175 03:33:44,603 --> 03:33:44,803 OKAY. 4176 03:33:44,803 --> 03:33:46,104 SO WE'LL MOVE ON NOW. 4177 03:33:46,104 --> 03:33:53,111 THE NEXT SPEAKER IS JULIA 4178 03:33:53,111 --> 03:34:01,686 PILITSIS. 4179 03:34:01,686 --> 03:34:05,757 -- IS JULIE PILITSIS. 4180 03:34:05,757 --> 03:34:14,466 >> I THINK IT'S STILL SHARING. 4181 03:34:14,466 --> 03:34:17,702 OH, I GOT THE THUMBS UP. 4182 03:34:17,702 --> 03:34:19,504 >> THANK YOU ALL FOR ATTENDING 4183 03:34:19,504 --> 03:34:20,505 THIS AND THANK YOU TO THE 4184 03:34:20,505 --> 03:34:21,506 PLANNING COMMITTEE FOR THE 4185 03:34:21,506 --> 03:34:23,141 OPPORTUNITY TO BE HERE TODAY. 4186 03:34:23,141 --> 03:34:25,210 I'M EXCITED TO TALK TO YOU 4187 03:34:25,210 --> 03:34:28,280 SPECIFICALLY ABOUT CHRONIC PAIN 4188 03:34:28,280 --> 03:34:32,083 AND MY MODEL SYSTEM, WHICH IS 4189 03:34:32,083 --> 03:34:32,317 HUMANS. 4190 03:34:32,317 --> 03:34:35,186 IN TERMS OF MY DISCLOSURES, YOU 4191 03:34:35,186 --> 03:34:38,490 KNOW, SOME OF THESE ARE RELEVANT 4192 03:34:38,490 --> 03:34:39,891 TO THE TRAINING AND EDUCATION IN 4193 03:34:39,891 --> 03:34:42,761 THIS TRAINING, AS WELL AS MY 4194 03:34:42,761 --> 03:34:42,994 FUNDING. 4195 03:34:42,994 --> 03:34:45,030 SO WHEN WE THINK ABOUT CHRONIC 4196 03:34:45,030 --> 03:34:46,798 PAIN, I CAN'T THINK OF -- YOU 4197 03:34:46,798 --> 03:34:48,233 KNOW, I STARTED OUT AS I WAS 4198 03:34:48,233 --> 03:34:49,768 PRACTICING FOR THIS TALK TODAY 4199 03:34:49,768 --> 03:34:53,371 SAYING I CAN'T THINK OF ANY 4200 03:34:53,371 --> 03:34:54,706 DISEASE WHERE INTEROCEPTION IS 4201 03:34:54,706 --> 03:34:57,442 MORE RELEVANT BUT AS I'VE HEARD 4202 03:34:57,442 --> 03:34:59,844 MY COL LEAK SPEAK, THERE ARE SO 4203 03:34:59,844 --> 03:35:02,147 MANY PLACES THIS -- COLLEAGUES 4204 03:35:02,147 --> 03:35:03,682 SPEAK, THERE ARE SO MANY PLACES 4205 03:35:03,682 --> 03:35:04,849 THIS TOUCHES. 4206 03:35:04,849 --> 03:35:06,518 REALLY WHAT I'M HOPING TODAY IS 4207 03:35:06,518 --> 03:35:08,386 TO TALK A COUPLE OF YOU IN THE 4208 03:35:08,386 --> 03:35:09,654 AUDIENCE INTO THINKING ABOUT 4209 03:35:09,654 --> 03:35:10,555 CHRONIC PAIN BECAUSE THIS IS 4210 03:35:10,555 --> 03:35:12,090 REALLY SOMETHING THAT AFFECTS SO 4211 03:35:12,090 --> 03:35:14,326 MANY PEOPLE, UPWARDS OF 4212 03:35:14,326 --> 03:35:16,628 50 MILLION PEOPLE. 4213 03:35:16,628 --> 03:35:18,863 YOU KNOW, WE HAVE IMAGING AND 4214 03:35:18,863 --> 03:35:20,198 FUNCTIONAL IMAGING TO STUDY 4215 03:35:20,198 --> 03:35:21,499 THIS, BUT WE NEED BETTER TOOLS 4216 03:35:21,499 --> 03:35:23,468 AND WE NEED BETTER TECHNIQUES, 4217 03:35:23,468 --> 03:35:25,337 ESPECIALLY AS WE EXPAND OUR 4218 03:35:25,337 --> 03:35:26,638 MODEL SYSTEMS. 4219 03:35:26,638 --> 03:35:33,378 SO I'VE HAD A VARIETY OF -- 4220 03:35:33,378 --> 03:35:34,946 [PAUSE] THESE AND I'LL TALK A 4221 03:35:34,946 --> 03:35:35,246 LITTLE BIT. 4222 03:35:35,246 --> 03:35:37,148 ONE OF THE THING I DO AS A 4223 03:35:37,148 --> 03:35:40,652 NEUROSURGEON IS I IMPLANT SPINAL 4224 03:35:40,652 --> 03:35:41,953 CORD DEVICES IN THE EPIDURAL 4225 03:35:41,953 --> 03:35:43,955 SPACE THAT ALLOW FOR STIMULATING 4226 03:35:43,955 --> 03:35:45,790 SPINAL AND SOMATIC PATHWAYS, AND 4227 03:35:45,790 --> 03:35:47,425 AS MUCH AS SOME OF YOU HAVE 4228 03:35:47,425 --> 03:35:48,526 HEARD ABOUT DEEP BRAIN 4229 03:35:48,526 --> 03:35:49,728 STIMULATION AND HOW WE CAN DO 4230 03:35:49,728 --> 03:35:53,665 MANY STUDIES INTRAOPERATIVELY, 4231 03:35:53,665 --> 03:35:57,002 SIMILAR TO -- 4232 03:35:57,002 --> 03:36:00,305 ARE PLEXON IN RATS, DURING 4233 03:36:00,305 --> 03:36:01,473 SURGERY, WE CAN BETTER 4234 03:36:01,473 --> 03:36:02,273 UNDERSTAND ELECTROPHYSIOLOGY AND 4235 03:36:02,273 --> 03:36:04,109 REALLY HOW SPINAL AND SOMATIC 4236 03:36:04,109 --> 03:36:06,311 PATHWAYS CAN BE INVOLVED IN 4237 03:36:06,311 --> 03:36:06,644 INTEROCEPTION. 4238 03:36:06,644 --> 03:36:09,347 I KNOW MANY OF YOU HAVE SEEN 4239 03:36:09,347 --> 03:36:10,782 THIS CARTOON, YOU KNOW, QUICK 4240 03:36:10,782 --> 03:36:12,650 GOOGLE SEARCH, THIS IS WHAT POPS 4241 03:36:12,650 --> 03:36:12,817 UP. 4242 03:36:12,817 --> 03:36:14,519 I THINK IT'S REALLY INFORMATIVE 4243 03:36:14,519 --> 03:36:16,388 AS A CARTOON. 4244 03:36:16,388 --> 03:36:18,223 SO JUST THINKING ABOUT PAIN, 4245 03:36:18,223 --> 03:36:19,858 YOU'RE GOING TO TOUCH THE FLOWER 4246 03:36:19,858 --> 03:36:23,461 OR TOUCH THE THORN AND YOU SAY 4247 03:36:23,461 --> 03:36:23,695 OUCH. 4248 03:36:23,695 --> 03:36:25,897 AND WHERE IS THAT SIGNAL GOING? 4249 03:36:25,897 --> 03:36:28,199 SO IT STARTS ALTHOUGH YOUR 4250 03:36:28,199 --> 03:36:29,167 FINGER -- STARTS AT YOUR 4251 03:36:29,167 --> 03:36:30,602 FINGERTIPS AND TALKS ABOUT THE 4252 03:36:30,602 --> 03:36:31,903 PAIN RECEPTORS THAT WE HAVE ALL 4253 03:36:31,903 --> 03:36:34,639 THE WAY UP THE ARM TO THE 4254 03:36:34,639 --> 03:36:38,576 BRACHIAL PLEXUS, TO SPINAL CORD, 4255 03:36:38,576 --> 03:36:40,745 BRAINSTEM, RELAY STATIONS, BACK 4256 03:36:40,745 --> 03:36:43,815 DOWN THE DESCENDING PATHWAYS IN 4257 03:36:43,815 --> 03:36:45,784 ORDER TO HAVE THAT REACTION. 4258 03:36:45,784 --> 03:36:47,852 THAT'S WHAT HAPPENS IN YOU OR I 4259 03:36:47,852 --> 03:36:49,387 AND PEOPLE DHEENT SUFFER FROM 4260 03:36:49,387 --> 03:36:50,121 CHRONIC PAIN. 4261 03:36:50,121 --> 03:36:51,589 BUT ONE OF THE INTERESTING 4262 03:36:51,589 --> 03:36:53,124 THINGS ABOUT PAIN IS WHEN YOU 4263 03:36:53,124 --> 03:36:56,661 HAVE PAIN FROM MORE THAN -- PAIN 4264 03:36:56,661 --> 03:36:57,829 FOR MORE THAN THREE MONTHS, THE 4265 03:36:57,829 --> 03:36:59,697 WHOLE PATHWAY SHIFTS AND THIS 4266 03:36:59,697 --> 03:37:00,932 MECHANISM OF INTEROCEPTION 4267 03:37:00,932 --> 03:37:01,199 SWITCHES. 4268 03:37:01,199 --> 03:37:02,767 SO WE MAY NOT KNOW ENOUGH ABOUT 4269 03:37:02,767 --> 03:37:04,936 IT IN A NORMAL STATE, THEN WHEN 4270 03:37:04,936 --> 03:37:06,538 WE TAKE THE DISEASE STATE OF 4271 03:37:06,538 --> 03:37:09,541 CHRONIC PAIN, IT GETS EVEN MORE 4272 03:37:09,541 --> 03:37:11,076 COMPLEX. 4273 03:37:11,076 --> 03:37:12,577 SO ON THE LEFT ILLUSTRATES WHAT 4274 03:37:12,577 --> 03:37:14,245 I WAS SAYING IS HOW THIS CAN 4275 03:37:14,245 --> 03:37:18,083 AFFECT SO MANY PARTS AS YOU GO 4276 03:37:18,083 --> 03:37:20,718 OUT, BUT THEN -- AS YOU GO ON. 4277 03:37:20,718 --> 03:37:22,987 BUT THEN LET'S THINK ABOUT WHAT 4278 03:37:22,987 --> 03:37:25,190 HAPPENS DURING CENTRAL 4279 03:37:25,190 --> 03:37:26,324 SENSITIZATION AND MAKES US MORE 4280 03:37:26,324 --> 03:37:26,624 COMPLICATED. 4281 03:37:26,624 --> 03:37:27,392 EVERYBODY HAS DONE SOMETHING 4282 03:37:27,392 --> 03:37:28,359 WHERE THEY TWIST THEIR INC. HE 4283 03:37:28,359 --> 03:37:31,863 WILL OR HURT THEIR KNEE -- TWIST 4284 03:37:31,863 --> 03:37:33,264 THEIR ANKLE OR HURT THEIR KNEE. 4285 03:37:33,264 --> 03:37:34,265 WHAT HAPPENS? 4286 03:37:34,265 --> 03:37:36,267 YOU START LIMPING, FAVOR THE 4287 03:37:36,267 --> 03:37:38,002 OTHER SIDE, OTHER SIDE HURTS, 4288 03:37:38,002 --> 03:37:39,437 BACK IS OUT OF WHACK AND CAN'T 4289 03:37:39,437 --> 03:37:40,872 SLEEP AND YOU'RE MISERABLE AND 4290 03:37:40,872 --> 03:37:43,475 ALL THESE THINGS HAPPEN THAT 4291 03:37:43,475 --> 03:37:45,543 INVOLVE ACUTE PAIN AND HOW WE 4292 03:37:45,543 --> 03:37:46,878 FEEL IN THE INTEROCEPTION. 4293 03:37:46,878 --> 03:37:49,614 SO THIS CAN BE COMPENSATORY 4294 03:37:49,614 --> 03:37:52,884 OVERUSE, THIS CAN BE MUSCLE 4295 03:37:52,884 --> 03:37:53,118 SPASM. 4296 03:37:53,118 --> 03:37:55,086 THE MUSCLES CAN GET SO TIGHT, IN 4297 03:37:55,086 --> 03:37:56,387 FACT, THEY CAN COMPRESS THE 4298 03:37:56,387 --> 03:37:59,791 NERVES AND ALTER OUR RECEPTORS 4299 03:37:59,791 --> 03:38:01,092 AND INFLAMMATION AND WHOLE 4300 03:38:01,092 --> 03:38:02,427 SYSTEMIC PROCESSES CAN HAPPEN. 4301 03:38:02,427 --> 03:38:04,162 THIS IS NORMAL PAIN. 4302 03:38:04,162 --> 03:38:05,930 WHEN YOU GO INTO THE CHRONIC 4303 03:38:05,930 --> 03:38:08,666 PAIN CYCLE, ALL THOSE RESPONSES, 4304 03:38:08,666 --> 03:38:11,269 AGAIN, AND ALL THOSE WAYS WHERE 4305 03:38:11,269 --> 03:38:14,672 PAIN CAN OCCUR ARE ALTERED, AND 4306 03:38:14,672 --> 03:38:17,509 AGAIN, ADDING TO, YOU KNOW, JUST 4307 03:38:17,509 --> 03:38:19,210 THIS MULTI-LAYER COMPLEXITY WHEN 4308 03:38:19,210 --> 03:38:25,083 YOU LOOK AT THIS DISEASE. 4309 03:38:25,083 --> 03:38:29,220 I TOO LIKED DR. TYE'S FOMO 4310 03:38:29,220 --> 03:38:31,322 14R50EUD AND ONE OF THE 4311 03:38:31,322 --> 03:38:32,490 THINGS -- SLIDE AND ONE OF THE 4312 03:38:32,490 --> 03:38:33,491 THINGS I WAS THINKING ABOUT WHEN 4313 03:38:33,491 --> 03:38:35,460 SHE WAS TALKING ABOUT THIS IS 4314 03:38:35,460 --> 03:38:37,095 CHRONIC SPAIN A RESPONSE THAT IN 4315 03:38:37,095 --> 03:38:39,197 THAT CASE THE ANIMAL MIGHT HAVE 4316 03:38:39,197 --> 03:38:40,498 TO THE SITUATION OR THE HUMAN 4317 03:38:40,498 --> 03:38:43,434 HAS TO THEIR SITUATION, TWHING 4318 03:38:43,434 --> 03:38:45,170 YOU'LL ALSO NOTICE AND I DON'T 4319 03:38:45,170 --> 03:38:47,172 KNOW HOW YOU MIMIC THIS IN AN 4320 03:38:47,172 --> 03:38:48,473 ANIMAL MODEL, BUT I'M SURE 4321 03:38:48,473 --> 03:38:50,341 SHE'LL FIND OUT, IS WHEN YOU SEE 4322 03:38:50,341 --> 03:38:54,279 PATIENTS WITH CHRONIC PAIN, IT'S 4323 03:38:54,279 --> 03:38:55,880 ALMOST THEY'RE SO DIFFERENT, BUT 4324 03:38:55,880 --> 03:38:57,549 SOME OF THE BEHAVIORS YOU SEE IN 4325 03:38:57,549 --> 03:38:59,417 THE CLINIC ARE THE SAME. 4326 03:38:59,417 --> 03:39:01,619 IT GETS EXHAUSTING NOT ONLY FOR 4327 03:39:01,619 --> 03:39:03,588 THE PATIENT BUT FOR THE FAMILY 4328 03:39:03,588 --> 03:39:06,124 MEMBER, THE FAMILY MEMBERS 4329 03:39:06,124 --> 03:39:07,091 INEVITABLY IN THE BACK PLAYING 4330 03:39:07,091 --> 03:39:08,526 ON THEIR PHONE AND HOW DO YOU 4331 03:39:08,526 --> 03:39:09,294 ADDRESS THAT? 4332 03:39:09,294 --> 03:39:11,896 AND HOW CAN YOU MIMIC WHAT 4333 03:39:11,896 --> 03:39:13,665 THEY'RE FEELING IN THEIR WHOLE 4334 03:39:13,665 --> 03:39:15,733 ECOSYSTEM AS THEY RESPOND TO 4335 03:39:15,733 --> 03:39:15,967 THINGS? 4336 03:39:15,967 --> 03:39:17,635 WE DON'T HAVE GOOD TOOLS. 4337 03:39:17,635 --> 03:39:19,571 RIGHT NOW, YOU KNOW, WHEN WE 4338 03:39:19,571 --> 03:39:21,105 THINK ABOUT PAIN, WE'RE STILL ON 4339 03:39:21,105 --> 03:39:23,174 THE NUMERIC RATING SCALE SCORE, 4340 03:39:23,174 --> 03:39:24,842 OH, WHAT'S YOUR PAIN? 4341 03:39:24,842 --> 03:39:26,044 ONE THROUGH TEN. 4342 03:39:26,044 --> 03:39:27,412 THERE'S MULTIPLE REASONS WHY 4343 03:39:27,412 --> 03:39:28,846 THIS IS INEFFECTIVE. 4344 03:39:28,846 --> 03:39:30,748 THIS HAS BEEN SHOWN TO IRCHTD 4345 03:39:30,748 --> 03:39:31,950 DIFFERENT MEN AND WOMEN, IT 4346 03:39:31,950 --> 03:39:33,251 DEPENDS ON WHO ASKS THE 4347 03:39:33,251 --> 03:39:33,518 QUESTION. 4348 03:39:33,518 --> 03:39:35,653 OLDER PEOPLE ARE RELUCTANT TO 4349 03:39:35,653 --> 03:39:37,188 GIVE HIGHER PAIN SCALES BECAUSE 4350 03:39:37,188 --> 03:39:39,591 THEY THINK, YOU KNOW, THEIR 4351 03:39:39,591 --> 03:39:40,792 MORBIDITY AND MORTALITY IS 4352 03:39:40,792 --> 03:39:41,659 ASSOCIATED WITH IT. 4353 03:39:41,659 --> 03:39:43,962 SO THEN WE HAVE A WHOLE BATTERY 4354 03:39:43,962 --> 03:39:46,598 OF SUBJECTIVE TESTS THAT WE USE, 4355 03:39:46,598 --> 03:39:48,199 AND THIS GIVES US AN IDEA, AND 4356 03:39:48,199 --> 03:39:49,867 WE'VE BEEN ABLE TO DO SOME FUN 4357 03:39:49,867 --> 03:39:52,503 THINGS WITH PREDICTING OUTCOMES 4358 03:39:52,503 --> 03:39:54,138 WITH MACHINE LEARNING, BUT IT'S 4359 03:39:54,138 --> 03:39:56,207 STILL ASKING THE PATIENTS 4360 03:39:56,207 --> 03:39:58,843 SUBJECTIVELY HOW THEY'RE 4361 03:39:58,843 --> 03:39:59,344 FEELING. 4362 03:39:59,344 --> 03:40:01,446 WHEN DR. GARFUNKLE SPOKE EARLIER 4363 03:40:01,446 --> 03:40:04,549 TOO, YOU KNOW, WHEN SHE TALKED 4364 03:40:04,549 --> 03:40:05,984 ABOUT HOW PRECISION GOES UP AND 4365 03:40:05,984 --> 03:40:08,152 THEN AWARENESS GOES DOWN, WE'VE 4366 03:40:08,152 --> 03:40:10,355 PLAYED AROUND WITH SOME OF THE 4367 03:40:10,355 --> 03:40:12,423 INTEROCEPTION SCALES TOO IN OUR 4368 03:40:12,423 --> 03:40:13,625 PATIENTS, AND IT IS INTERESTING 4369 03:40:13,625 --> 03:40:15,360 BECAUSE ASPECTS OF INTEROCEPTION 4370 03:40:15,360 --> 03:40:16,394 CAN BE VERY HELPFUL. 4371 03:40:16,394 --> 03:40:18,763 BUT THEN IF YOU GET 4372 03:40:18,763 --> 03:40:20,398 HYPER-FOCUSED ON THINGS, IT CAN 4373 03:40:20,398 --> 03:40:23,034 REALLY BE TO YOUR DETRIMENT AS 4374 03:40:23,034 --> 03:40:23,601 WELL. 4375 03:40:23,601 --> 03:40:24,669 SO, YOU KNOW, THESE ARE THINGS 4376 03:40:24,669 --> 03:40:26,304 THAT WE ALL HAVE TO CONSIDER 4377 03:40:26,304 --> 03:40:27,939 WHEN WE'RE LOOKING AT THIS. 4378 03:40:27,939 --> 03:40:30,608 SO IN TERMS OF OBJECTIVE 4379 03:40:30,608 --> 03:40:32,110 MARKERS, STILL SO LIMITED, 4380 03:40:32,110 --> 03:40:33,444 FUNCTIONAL IMAGING, WE'VE 4381 03:40:33,444 --> 03:40:35,313 STARTED IN SPINAL CORD 4382 03:40:35,313 --> 03:40:36,481 STIMULATION TO AT LEAST BE ABLE 4383 03:40:36,481 --> 03:40:38,383 TO KNOW THAT WHAT WE'RE 4384 03:40:38,383 --> 03:40:40,685 DELIVERING TO RELIEVE PAIN IS 4385 03:40:40,685 --> 03:40:42,220 HITTING THE TARGET. 4386 03:40:42,220 --> 03:40:43,755 JUST SIMPLE PHYSIOLOGY, WE'RE 4387 03:40:43,755 --> 03:40:45,056 DELIVERING A STIMULUS AND WE 4388 03:40:45,056 --> 03:40:46,391 HAVE THIS CHANGE IN ACTION 4389 03:40:46,391 --> 03:40:47,625 POTENTIAL THAT YOU SEE ON THE 4390 03:40:47,625 --> 03:40:48,459 RIGHT SIDE. 4391 03:40:48,459 --> 03:40:50,628 THAT TELLS ME THAT I'M GETTING 4392 03:40:50,628 --> 03:40:51,829 THE STIMULUS THERE, DOESN'T SAY 4393 03:40:51,829 --> 03:40:53,698 A THING ABOUT PAIN RELIEF, BUT 4394 03:40:53,698 --> 03:40:55,233 AT LEAST I KNOW THAT I'M 4395 03:40:55,233 --> 03:40:56,134 DELIVERING SOMETHING. 4396 03:40:56,134 --> 03:41:01,706 SO HOW CAN WE KNOW HOW THIS CAN 4397 03:41:01,706 --> 03:41:04,108 AFFECT PAIN RELIEF? 4398 03:41:04,108 --> 03:41:05,877 SO I HAVE, WE'RE FORTUNATE 4399 03:41:05,877 --> 03:41:09,147 ENOUGH THAT WHEN I STARTED 4400 03:41:09,147 --> 03:41:10,515 PRACTICE, I MADE A GOOD DECISION 4401 03:41:10,515 --> 03:41:11,949 AND STARTED A DATABASE OF ALL 4402 03:41:11,949 --> 03:41:13,651 THE PATIENTS I HAD I AM 4403 03:41:13,651 --> 03:41:14,719 IMPLANTED WITH THESE DEVICES AND 4404 03:41:14,719 --> 03:41:20,291 DID MULTIARE -- MULTIPLE 4405 03:41:20,291 --> 03:41:21,392 BATTERIES, BEFORE SURGERY, THREE 4406 03:41:21,392 --> 03:41:23,494 MONTHS, SIX MONTHS, NINE MONTHS, 4407 03:41:23,494 --> 03:41:26,731 TWELVE MONTHS, SO ON. 4408 03:41:26,731 --> 03:41:28,066 WE HAVE SUBJECTIVE DATA AND 4409 03:41:28,066 --> 03:41:29,400 STARTED LOOKING AT OBJECTIVE 4410 03:41:29,400 --> 03:41:29,967 DATA. 4411 03:41:29,967 --> 03:41:31,936 HIGH RESOLUTION G, WE WERE ALSO 4412 03:41:31,936 --> 03:41:35,106 FORTUNATE TO WORK WITH A HIGH 4413 03:41:35,106 --> 03:41:36,741 RESOLUTION SPINAL CORD 4414 03:41:36,741 --> 03:41:38,276 STIMULATION PANEL AND THEN WE 4415 03:41:38,276 --> 03:41:40,345 TRACK OUTCOMES USING THOSE 4416 03:41:40,345 --> 03:41:41,713 PROSPECTIVELY AND LONGITUDINALLY 4417 03:41:41,713 --> 03:41:42,880 TO SEE IF WE COULD MAKE ANY 4418 03:41:42,880 --> 03:41:45,717 PREDICTIONS ABOUT WHAT PEOPLE 4419 03:41:45,717 --> 03:41:47,251 ARE FEELING. 4420 03:41:47,251 --> 03:41:51,089 SO ROUTINELY WHEN I ROUTINE 4421 03:41:51,089 --> 03:41:53,157 THESE SURGERIES I USE 4422 03:41:53,157 --> 03:41:53,925 INTRAOPERATIVE MONITORING AND 4423 03:41:53,925 --> 03:41:55,660 WHAT WE DO IS ONE THIS CAN BE 4424 03:41:55,660 --> 03:41:57,795 USED FOR SAFETY BUT TWO THIS CAN 4425 03:41:57,795 --> 03:41:59,197 ALSO BE USED TO DELIVER SIGNAL 4426 03:41:59,197 --> 03:42:01,599 TO THE EPIDURAL SPACE, HERE IS 4427 03:42:01,599 --> 03:42:03,901 OUR HIGH RESOLUTION PANEL EIGHT 4428 03:42:03,901 --> 03:42:05,236 COLUMNS, MEDIAL LATERALLY, 4429 03:42:05,236 --> 03:42:06,738 GENERALLY WE PUT THESE IN THE 4430 03:42:06,738 --> 03:42:08,506 THORACIC LEVEL, AND WE CAN SAY, 4431 03:42:08,506 --> 03:42:09,741 OKAY, WE'RE GOING TO STIMULATE 4432 03:42:09,741 --> 03:42:10,375 THROUGH THAT. 4433 03:42:10,375 --> 03:42:12,777 DO WE GET A RESPONSE THAT 4434 03:42:12,777 --> 03:42:13,978 CORRESPONDS WITH THE DERMATOME 4435 03:42:13,978 --> 03:42:15,947 WHERE THE PATIENT HAS PAIN? 4436 03:42:15,947 --> 03:42:19,450 WE ALSO PUT A SWIM CAP ON THAT'S 4437 03:42:19,450 --> 03:42:21,419 HIGH RESOLUTION EEG AND THE IDEA 4438 03:42:21,419 --> 03:42:23,388 HERE IS WE'RE TIME STAMPING THAT 4439 03:42:23,388 --> 03:42:24,489 RESPONSE IN THE SPINAL CORD TO 4440 03:42:24,489 --> 03:42:28,993 WHAT'S GOING ON IN THE BRAIN. 4441 03:42:28,993 --> 03:42:30,728 THERE'S A TON OF DATA THAT WE 4442 03:42:30,728 --> 03:42:31,362 GET. 4443 03:42:31,362 --> 03:42:32,964 DR. COLEMAN PRESENTED EARLIER, 4444 03:42:32,964 --> 03:42:34,799 AND HE KIND OF BREEZED THROUGH 4445 03:42:34,799 --> 03:42:36,100 ALL THE STUFF THAT HE WAS DOING, 4446 03:42:36,100 --> 03:42:37,835 AND I WAS JUST GOING, OH, MY 4447 03:42:37,835 --> 03:42:38,736 GOSH, THAT'S SO MUCH DATA AND 4448 03:42:38,736 --> 03:42:39,937 THAT'S SO MUCH WORK JUST IT EVEN 4449 03:42:39,937 --> 03:42:41,339 GET THE DATA POINTS BECAUSE 4450 03:42:41,339 --> 03:42:44,509 EVERY TIME YOU STIMULATE WITH AN 4451 03:42:44,509 --> 03:42:45,209 ELECTRIC ELECTRICAL DEVICE, YOU 4452 03:42:45,209 --> 03:42:47,044 KNOW WHAT HAPPENS, A TON OF 4453 03:42:47,044 --> 03:42:47,912 ARTIFACT COMES OUT AND ONE OF 4454 03:42:47,912 --> 03:42:50,348 THE HARDEST PARTS IN THIS FIELD 4455 03:42:50,348 --> 03:42:51,883 IS KNOWING HOW TO FILTER THIS 4456 03:42:51,883 --> 03:42:53,885 AND HOW TO PROCESS THIS, AND YOU 4457 03:42:53,885 --> 03:42:55,686 WANT TO GET RID OF THE ARTIFACT 4458 03:42:55,686 --> 03:42:57,221 BUT YOU DON'T WANT TO LOSE THE 4459 03:42:57,221 --> 03:42:58,589 IMPORTANT PARTS OF THE SIGNAL. 4460 03:42:58,589 --> 03:43:02,827 YOU WANT TO BE ABLE TO VISUALIZE 4461 03:43:02,827 --> 03:43:03,928 THIS SO YOU CAN SEE HOW MUCH 4462 03:43:03,928 --> 03:43:05,696 DATA YOU'RE DEALING WITH. 4463 03:43:05,696 --> 03:43:07,565 SO WHAT WE'VE DONE IS CREATED 4464 03:43:07,565 --> 03:43:10,301 GRAPHICAL USER INTERFACES, GONE 4465 03:43:10,301 --> 03:43:14,238 THROUGH AND LOOKED AT A VARIETY 4466 03:43:14,238 --> 03:43:16,207 OF DIFFERENT PROCESSING 4467 03:43:16,207 --> 03:43:17,408 TECHNIQUES TO GET WHERE WE 4468 03:43:17,408 --> 03:43:18,075 NEEDED TO GO. 4469 03:43:18,075 --> 03:43:20,678 SO THIS IS AN EXAMPLE OF US 4470 03:43:20,678 --> 03:43:22,647 LOOKING AT A MAXIMUM ROOT MEAN 4471 03:43:22,647 --> 03:43:22,880 SQUARE. 4472 03:43:22,880 --> 03:43:26,150 WE HAD THE ROUTINE DEVICES THAT 4473 03:43:26,150 --> 03:43:28,119 WE IMPLANT FOR SPINAL CORD 4474 03:43:28,119 --> 03:43:30,988 STIMULATION AND THIS HIGH 4475 03:43:30,988 --> 03:43:32,657 RESOLUTION PADDLE. 4476 03:43:32,657 --> 03:43:33,925 WHY I WANT TO SHOW YOU THIS, IF 4477 03:43:33,925 --> 03:43:36,360 WE LOOK AT T6 AND LOOK AT THE 4478 03:43:36,360 --> 03:43:37,995 HIGH RESOLUTION PADDLE, IT HAD 4479 03:43:37,995 --> 03:43:39,197 EIGHT CONTACTS, COMMERCIAL 4480 03:43:39,197 --> 03:43:40,498 PADDLE ONLY HAS ABOUT FOUR 4481 03:43:40,498 --> 03:43:42,233 CONTACTS OR FOUR CLUSMS THAT 4482 03:43:42,233 --> 03:43:43,468 WE'RE LOOKING -- COLUMN THAT 4483 03:43:43,468 --> 03:43:46,604 WE'RE LOOKING AT, WE ARE ABLE ON 4484 03:43:46,604 --> 03:43:50,575 THE Y AXIS TO SEE ALL THOSE 4485 03:43:50,575 --> 03:43:51,776 INDIVIDUAL MUSCLE GROUPS THAT 4486 03:43:51,776 --> 03:43:56,247 WE'RE STIMULATING WITH THIS 4487 03:43:56,247 --> 03:43:56,581 DEVICE. 4488 03:43:56,581 --> 03:43:58,049 NOW, WHY IS THIS IMPORTANT? 4489 03:43:58,049 --> 03:44:02,286 JUST AS THE BRAIN HAS A 4490 03:44:02,286 --> 03:44:03,254 MEMUNCULUS WHEN YOU THINK ABOUT 4491 03:44:03,254 --> 03:44:04,789 THE CORTEX, I WOULD ARGUE THAT 4492 03:44:04,789 --> 03:44:06,357 THE SPINAL CORD DOES TOO, EXCEPT 4493 03:44:06,357 --> 03:44:07,758 THERE ARE SO MANY LEVELS OF IT, 4494 03:44:07,758 --> 03:44:09,193 IT VARIES FROM PLACE TO PLACE. 4495 03:44:09,193 --> 03:44:11,262 AND UNLESS WE START LOOKING AND 4496 03:44:11,262 --> 03:44:12,563 DEVELOPING TOOLS IN ORDER TO DO 4497 03:44:12,563 --> 03:44:14,966 THIS, IT WILL BE REALLY HARD TO 4498 03:44:14,966 --> 03:44:16,767 UNDERSTAND THE SOMATIC PATHWAYS 4499 03:44:16,767 --> 03:44:18,569 AND THE ROLE IN INTEROCEPTION AS 4500 03:44:18,569 --> 03:44:22,440 WELL AS OTHER THINGS, YOU KNOW, 4501 03:44:22,440 --> 03:44:23,841 SPINAL CORD STIMULATION IS ALSO 4502 03:44:23,841 --> 03:44:25,710 USED FOR SPINAL CORD INJURY. 4503 03:44:25,710 --> 03:44:27,545 HOWEVER, THAT HAS A DRAMATIC EE 4504 03:44:27,545 --> 03:44:28,980 IF HE CAN ON THE AUTONOMIC 4505 03:44:28,980 --> 03:44:30,848 SYSTEM, HOW ARE WE GOING TO KNOW 4506 03:44:30,848 --> 03:44:31,716 WHAT TO DO THERE? 4507 03:44:31,716 --> 03:44:33,351 SO THIS IS REALLY IMPORTANT. 4508 03:44:33,351 --> 03:44:34,485 SIMULTANEOUSLY, WE LOOKED AT 4509 03:44:34,485 --> 03:44:38,756 THIS HIGH RESOLUTION EEG. 4510 03:44:38,756 --> 03:44:41,392 SO THE DATA ON THE RIGHT IS 4511 03:44:41,392 --> 03:44:42,793 ACTUALLY FROM PATIENTS WHERE WE 4512 03:44:42,793 --> 03:44:49,066 DID THIS PREOP -- AND THEN AT 4513 03:44:49,066 --> 03:44:50,701 THREE MONTHS POSTOP S IN THE 4514 03:44:50,701 --> 03:44:52,970 BRAIN, DIFFERENT REGIONS, WE 4515 03:44:52,970 --> 03:44:56,274 CAN'T WITH EEG LOOK AT THE 4516 03:44:56,274 --> 03:44:57,475 INSULA OR THALAMUS BUT WE CAN 4517 03:44:57,475 --> 03:44:59,544 LOOK AT MULTIPLE CORTICAL 4518 03:44:59,544 --> 03:45:01,946 REGIONS, THIS IS LOOKING AT THE 4519 03:45:01,946 --> 03:45:03,414 SOMATOSENSORY CORTEX. 4520 03:45:03,414 --> 03:45:05,349 AT THE BOTTOM OF THE RIGHT-HAND 4521 03:45:05,349 --> 03:45:07,518 SIDE OF THE SLIDE WE SEE 4522 03:45:07,518 --> 03:45:08,519 NONRESPONDERS THOSE AT THREE 4523 03:45:08,519 --> 03:45:09,954 MONTHS THAT DON'T HAVE RELIEF OF 4524 03:45:09,954 --> 03:45:12,690 THEIR PAIN HAVE SIMILAR SENSORY 4525 03:45:12,690 --> 03:45:14,759 DISTRIBUTION FROM PRE AND POSTOP 4526 03:45:14,759 --> 03:45:16,527 IN SOMATOSENSORY CORTEX, YOU SEE 4527 03:45:16,527 --> 03:45:17,495 THE DIFFERENCES BETWEEN THE 4528 03:45:17,495 --> 03:45:19,263 PURPLE AND GREEN LINE ON THE TOP 4529 03:45:19,263 --> 03:45:20,565 FOR THE RESPONDERS. 4530 03:45:20,565 --> 03:45:22,867 SO THIS IS EXCITING BECAUSE THIS 4531 03:45:22,867 --> 03:45:24,936 IS ACTUALLY CORRELATING WITH A 4532 03:45:24,936 --> 03:45:26,137 RESPONSE, AS OPPOSED TO SOME OF 4533 03:45:26,137 --> 03:45:28,005 THE THINGS THAT ARE DONE WITH 4534 03:45:28,005 --> 03:45:29,340 ECAP THAT ARE JUST TELLING YOU 4535 03:45:29,340 --> 03:45:30,841 THAT THE SIGNAL IS GETTING HERE. 4536 03:45:30,841 --> 03:45:32,743 NOW WE'RE STARLGT TO HAVE 4537 03:45:32,743 --> 03:45:33,544 ELECTROPHYSIOLOGICAL RESPONSES 4538 03:45:33,544 --> 03:45:36,213 THAT CORRELATE WITH PAIN RELIEF 4539 03:45:36,213 --> 03:45:39,283 AND HOW ALL THE PATHWAYS WORK 4540 03:45:39,283 --> 03:45:40,217 TOGETHER. 4541 03:45:40,217 --> 03:45:41,886 SO I JUST WANTED TO TOUCH UPON, 4542 03:45:41,886 --> 03:45:44,455 YOU KNOW, I TALKED ABOUT SPIEBL 4543 03:45:44,455 --> 03:45:46,857 CORD STIMULATION -- SPINAL CORD 4544 03:45:46,857 --> 03:45:47,158 STIMULATION. 4545 03:45:47,158 --> 03:45:50,294 I LIKE ARDEM AND EXTREMELY 4546 03:45:50,294 --> 03:45:53,965 EXCITED ABOUT THE DORSAL ROOT 4547 03:45:53,965 --> 03:45:55,032 GANGLIA AS WELL. 4548 03:45:55,032 --> 03:45:58,035 WE HAVE DEVICES AVAILABLE IN THE 4549 03:45:58,035 --> 03:46:00,771 CLINIC FDA APPROVED WHERE WE 4550 03:46:00,771 --> 03:46:01,973 IMPLANT PATIENTS WITH 4551 03:46:01,973 --> 03:46:04,375 STIMULATORS ON THE DORSAL ROOT 4552 03:46:04,375 --> 03:46:05,142 GANGLION, THESE ARE THE LEADS 4553 03:46:05,142 --> 03:46:07,111 THAT GO OUT ON THE X-RAY THROUGH 4554 03:46:07,111 --> 03:46:07,778 THE FORAMEN. 4555 03:46:07,778 --> 03:46:09,080 THESE ARE A LITTLE BIT OF 4556 03:46:09,080 --> 03:46:10,514 CHALLENGE FOR SURGEONS TO PUT IN 4557 03:46:10,514 --> 03:46:12,149 JUST BECAUSE SOMETIMES WE CAN'T 4558 03:46:12,149 --> 03:46:13,584 VISUALIZE THE ANATOMY. 4559 03:46:13,584 --> 03:46:15,653 BUT WHY DID I KEEP DOING THIS? 4560 03:46:15,653 --> 03:46:17,088 THE PATIENTS WERE DOING 4561 03:46:17,088 --> 03:46:18,623 REMARKABLY WELL. 4562 03:46:18,623 --> 03:46:20,358 SO THIS WAS GREAT FOR 4563 03:46:20,358 --> 03:46:21,025 DERMATOMES, RIGHT? 4564 03:46:21,025 --> 03:46:22,560 SO YOU'RE ONLY GOING TO BE ABLE 4565 03:46:22,560 --> 03:46:24,629 TO TARGET CERTAIN DERMATOMES 4566 03:46:24,629 --> 03:46:25,830 WITH THIS THERAPY. 4567 03:46:25,830 --> 03:46:28,132 BUT WE HAVE THIS BARRIER TO USE 4568 03:46:28,132 --> 03:46:31,302 BECAUSE IT'S REALLY HARD TO DO. 4569 03:46:31,302 --> 03:46:32,737 SO ELECTRICAL STIMULATION IS NOT 4570 03:46:32,737 --> 03:46:34,605 THE ONLY WAY TO MODULATE THIS. 4571 03:46:34,605 --> 03:46:36,340 WHAT WE STARTED WORKING ON AS 4572 03:46:36,340 --> 03:46:39,176 PART OF THE BLUEPRINT PROJECT 4573 03:46:39,176 --> 03:46:41,379 WAS FOCUSED ULTRASOUND DEVICE 4574 03:46:41,379 --> 03:46:43,247 TARGETING THE DORSAL ROOT 4575 03:46:43,247 --> 03:46:44,982 GANGLION IN ORDER TO MIMIC WHAT 4576 03:46:44,982 --> 03:46:46,751 WE WERE SEEING IN DERMATOMAL 4577 03:46:46,751 --> 03:46:46,951 PAIN. 4578 03:46:46,951 --> 03:46:49,353 SO WHAT WE DID WAS IN SWINE, WE 4579 03:46:49,353 --> 03:46:51,789 TOOK A MODEL WHERE, YOU KNOW, 4580 03:46:51,789 --> 03:46:53,524 THE WE DID BEHAVIORAL TESTING, 4581 03:46:53,524 --> 03:46:55,726 CREATED A LESION TYING OFF THE 4582 03:46:55,726 --> 03:46:56,894 COMMON PERONEAL NERVE, DID SOME 4583 03:46:56,894 --> 03:46:58,129 MORE BEHAVIORAL TESTING AND THEN 4584 03:46:58,129 --> 03:47:00,398 CAN A THREE-MINUTE TREATMENT 4585 03:47:00,398 --> 03:47:02,833 WITH THIS FOCUSED URLT SOUND 4586 03:47:02,833 --> 03:47:04,802 DEVICE TO -- ULTRASOUND DEVICE 4587 03:47:04,802 --> 03:47:06,037 TO NEURO MODULATE THE TISSUE. 4588 03:47:06,037 --> 03:47:07,638 WE WERE ABLE TO SEE A VARIETY OF 4589 03:47:07,638 --> 03:47:09,273 THINGS D A VARIETY OF RAT WORK 4590 03:47:09,273 --> 03:47:11,342 BEFORE WE GOT HERE WITH CAUDAL 4591 03:47:11,342 --> 03:47:14,211 AND DISTAL CHANGES IN PATHWAYS, 4592 03:47:14,211 --> 03:47:15,746 BUT, YOU KNOW, SOMETIMES A 4593 03:47:15,746 --> 03:47:17,281 PICTURE IS WORTH 1,000 WORDS. 4594 03:47:17,281 --> 03:47:18,716 SO I JUST WANTED TO TALK A 4595 03:47:18,716 --> 03:47:22,653 LITTLE BIT ABOUT THE VALUE OF 4596 03:47:22,653 --> 03:47:23,854 LARGE ANIMAL MODEL INSIDE THIS 4597 03:47:23,854 --> 03:47:24,055 SPACE. 4598 03:47:24,055 --> 03:47:25,156 I THINK IT CAN BE REALLY 4599 03:47:25,156 --> 03:47:25,423 IMPORTANT. 4600 03:47:25,423 --> 03:47:27,658 THIS IS OUR PIG WHEN WE WERE 4601 03:47:27,658 --> 03:47:29,860 JUST GETTING USED TO DOING THE 4602 03:47:29,860 --> 03:47:31,295 LIGATION MODEL. SO WE PULLED A 4603 03:47:31,295 --> 03:47:32,697 LITTLE TOO TIGHT AND GAVE HIM A 4604 03:47:32,697 --> 03:47:34,465 LITTLE BIT OF A FOOT DROP THERE, 4605 03:47:34,465 --> 03:47:36,867 BUT AGAIN, ONE THREE-MINUTE 4606 03:47:36,867 --> 03:47:38,302 DPREEMENT WE CHANGED A LOT OF 4607 03:47:38,302 --> 03:47:38,536 THINGS. 4608 03:47:38,536 --> 03:47:41,305 ONE THING THAT'S NEAT ABOUT PIGS 4609 03:47:41,305 --> 03:47:43,274 IS THEY MIMIC SOME HUMAN 4610 03:47:43,274 --> 03:47:43,808 BEHAVIOR. 4611 03:47:43,808 --> 03:47:45,342 SO THEY GUARD. 4612 03:47:45,342 --> 03:47:46,577 LIKE WHEN YOU HAVE, YOU HURT 4613 03:47:46,577 --> 03:47:47,878 YOUR ARM AND YOU DON'T WANT 4614 03:47:47,878 --> 03:47:49,280 SOMEBODY TO BUMP INTO T YOU GO 4615 03:47:49,280 --> 03:47:50,047 LIKE THIS. 4616 03:47:50,047 --> 03:47:52,450 PIGS WILL DO THE SAME THING. 4617 03:47:52,450 --> 03:47:57,722 THIS TREATMENT STOPPED THEM FROM 4618 03:47:57,722 --> 03:47:57,988 GUARDING. 4619 03:47:57,988 --> 03:48:03,427 SO HERE IS HIM AFTER. 4620 03:48:03,427 --> 03:48:04,829 AND WE LOOK FORWARD IN THIS 4621 03:48:04,829 --> 03:48:06,497 STAGE OF BLUEPRINT TO GETTING 4622 03:48:06,497 --> 03:48:08,466 THIS TO HUSM STUDIES. 4623 03:48:08,466 --> 03:48:10,568 -- TO HUMAN STUDIES. 4624 03:48:10,568 --> 03:48:13,370 SO AGAIN, I KNOW I'M TOTALLY 4625 03:48:13,370 --> 03:48:15,072 BIASED, BUT INTEROCEPTION AND 4626 03:48:15,072 --> 03:48:17,541 CHRONIC PAIN, YOU KNOW, ARE SO 4627 03:48:17,541 --> 03:48:18,943 RELATED, AND WE NEED TO ANSWER A 4628 03:48:18,943 --> 03:48:20,711 LOT OF THE QUESTIONS IN ORDER TO 4629 03:48:20,711 --> 03:48:22,113 SUCCESSFULLY TREAT THESE 4630 03:48:22,113 --> 03:48:22,379 PATIENTS. 4631 03:48:22,379 --> 03:48:24,215 WE NEED TO DEVELOP BETTER TOOLS 4632 03:48:24,215 --> 03:48:26,283 TO DO THIS. 4633 03:48:26,283 --> 03:48:28,018 LARGE ANIMAL MODELS AS WELL AS 4634 03:48:28,018 --> 03:48:28,986 HUMANS ARE IMPORTANT. 4635 03:48:28,986 --> 03:48:30,454 AND IF YOU NEED TO CHANGE 4636 03:48:30,454 --> 03:48:33,057 ANYTHING ABOUT YOUR OWN 4637 03:48:33,057 --> 03:48:34,925 INTEROCEPTION, YOU KNOW, NOW AND 4638 03:48:34,925 --> 03:48:36,794 ACUTELY, SOME OF THOSE BREATHING 4639 03:48:36,794 --> 03:48:38,863 EXERCISES OR MINDFULNESS-BASED 4640 03:48:38,863 --> 03:48:40,831 THERAPIES ARE THE WAY TO DO THAT 4641 03:48:40,831 --> 03:48:40,998 NOW. 4642 03:48:40,998 --> 03:48:45,002 I HAVE A LARGE TEAM, A BIG 4643 03:48:45,002 --> 03:48:49,039 THANKS TO DR. QUINTERO WHO IS IN 4644 03:48:49,039 --> 03:48:50,508 THE AUDIENCE AND HAD A POSTER 4645 03:48:50,508 --> 03:48:51,876 TOAD AS WELL AS A NUMBER OF MY 4646 03:48:51,876 --> 03:48:52,543 TEAM MEMBERS. 4647 03:48:52,543 --> 03:48:54,078 IF YOU WANT TO LEARN MORE ABOUT 4648 03:48:54,078 --> 03:48:56,046 HOW PAIN AND THE HUMAN SYSTEM 4649 03:48:56,046 --> 03:48:58,682 INTERACT BETWEEN DID I NITIONS, 4650 03:48:58,682 --> 03:49:08,192 SCIENTISTS AND ENGINEERS -- 4651 03:49:08,192 --> 03:49:09,827 BETWEEN CLINICIANS, SCIENTISTS 4652 03:49:09,827 --> 03:49:11,428 AND ENGINEERS. 4653 03:49:11,428 --> 03:49:12,096 THANK YOU VERY MUCH. 4654 03:49:12,096 --> 03:49:14,331 >> WE HAVE TIME FOR ONE 4655 03:49:14,331 --> 03:49:14,598 QUESTION. 4656 03:49:14,598 --> 03:49:15,199 ALL RIGHT. 4657 03:49:15,199 --> 03:49:16,834 THANK YOU VERY MUCH AGAIN, 4658 03:49:16,834 --> 03:49:17,034 JULIE. 4659 03:49:17,034 --> 03:49:17,568 >> THANK YOU. 4660 03:49:17,568 --> 03:49:27,812 >> THANK YOU. 4661 03:49:33,884 --> 03:49:35,653 >> HEY, EVERYBODY, THANKS. 4662 03:49:35,653 --> 03:49:37,721 IT'S A GREAT PLEASURE TO BE HERE 4663 03:49:37,721 --> 03:49:38,923 AND HONOR TO BE PART OF THIS 4664 03:49:38,923 --> 03:49:39,156 MEETING. 4665 03:49:39,156 --> 03:49:41,892 THIS TALK IS GOING TO BE A DATA 4666 03:49:41,892 --> 03:49:43,494 LIGHT TALK EXPIT COMING TO 4667 03:49:43,494 --> 03:49:43,761 TRACTION. 4668 03:49:43,761 --> 03:49:45,596 SO I'LL TELL YOU WHAT THAT MEANS 4669 03:49:45,596 --> 03:49:46,597 IT A SECOND. 4670 03:49:46,597 --> 03:49:48,465 SO I'M UP HERE REPRESENTING A 4671 03:49:48,465 --> 03:49:50,734 TEAM OF PEOPLE. 4672 03:49:50,734 --> 03:49:52,837 ON THIS SLIDE ARE SHOWN PI'S OF 4673 03:49:52,837 --> 03:49:54,371 THE GRANT AND THE STUDY I'LL 4674 03:49:54,371 --> 03:49:58,409 TALK B RESEARCH EVALUATING VAGAL 4675 03:49:58,409 --> 03:49:59,610 EXCITATION AND ANATOMICAL LINKS 4676 03:49:59,610 --> 03:50:01,679 IN HUMANS, REVEAL STUDY. 4677 03:50:01,679 --> 03:50:05,382 MYSELF, Z I AD NAHAS OVER HERE 4678 03:50:05,382 --> 03:50:07,384 FROM THE DCHT PSYCHIATRY 4679 03:50:07,384 --> 03:50:14,825 BEHAVIORAL SCIENCES, HUBERT LIM, 4680 03:50:14,825 --> 03:50:20,664 SAYEED IKRAMUDDIN, LYNN EBERLY, 4681 03:50:20,664 --> 03:50:21,298 VAUGHAN MACEFIELD. 4682 03:50:21,298 --> 03:50:24,902 THIS STUDY FUNDED BY NIH, VAGAL 4683 03:50:24,902 --> 03:50:26,337 RESEARCH AND GET TO 4684 03:50:26,337 --> 03:50:27,104 INTEROCEPTION IN A SECOND. 4685 03:50:27,104 --> 03:50:29,506 THIS IS WHERE IT STARTED 4686 03:50:29,506 --> 03:50:29,840 DECEMBER 2021. 4687 03:50:29,840 --> 03:50:32,476 THERE WAS A FUNDING OPPORTUNITY 4688 03:50:32,476 --> 03:50:36,180 ANNOUNCEMENT, CALLED VESPA, VNS 4689 03:50:36,180 --> 03:50:37,147 ENDPOINTS FROM STANDARDIZED 4690 03:50:37,147 --> 03:50:38,582 PROGRAM TERDZ, WHICH IS 4691 03:50:38,582 --> 03:50:43,387 OBVIOUSLY VESPA RED ON THE LEFT 4692 03:50:43,387 --> 03:50:45,155 AND ITALIAN FOR WATCH ON THE 4693 03:50:45,155 --> 03:50:45,356 RIGHT. 4694 03:50:45,356 --> 03:50:47,424 HERE IS WHAT PUT OUT A STUDY TO 4695 03:50:47,424 --> 03:50:47,591 DO. 4696 03:50:47,591 --> 03:50:49,627 THE PURPOSE OF THE FOA IS TO 4697 03:50:49,627 --> 03:50:52,429 SOLICIT APPLICATIONS FOR A U54 4698 03:50:52,429 --> 03:50:55,432 RESEARCH CENTER, TO CONDUCT A 4699 03:50:55,432 --> 03:50:56,934 LARGE MULTISITE CLINICAL STUDY 4700 03:50:56,934 --> 03:50:58,903 OF THE MULTIORGAN EFFECT OF 4701 03:50:58,903 --> 03:51:01,138 VAGUS NERVE STIMULATION, AS MANY 4702 03:51:01,138 --> 03:51:02,773 ORGAN SYSTEMS AS YOU CAN ENGAGE 4703 03:51:02,773 --> 03:51:04,842 WITH VAGAL STIMULATION IN 4704 03:51:04,842 --> 03:51:06,277 RESPONSE TO STANDARDIZED RANGE 4705 03:51:06,277 --> 03:51:07,144 OF PARAMETERS. 4706 03:51:07,144 --> 03:51:08,445 DATA WILL BE SHARED PUBLICLY FOR 4707 03:51:08,445 --> 03:51:09,647 EVERYONE TO GET WHEN WE'RE DONE 4708 03:51:09,647 --> 03:51:12,283 AND TO INFORM HOW TO OPTIMIZE 4709 03:51:12,283 --> 03:51:13,484 VAGAL NERVE STIMULATION FOR THE 4710 03:51:13,484 --> 03:51:15,119 TREATMENT OF A VARIETY OF 4711 03:51:15,119 --> 03:51:15,786 THINGS, RIGHT? 4712 03:51:15,786 --> 03:51:18,088 AND THEN LOOK AT HOW IT AFFECTS 4713 03:51:18,088 --> 03:51:19,390 SYSTEMS PHYSIOLOGY AND THE 4714 03:51:19,390 --> 03:51:21,025 FUNCTIONAL CONNECTIVITY OF THE 4715 03:51:21,025 --> 03:51:21,792 VAGUS NERVE. 4716 03:51:21,792 --> 03:51:23,961 I'M UP HERE BECAUSE THANK GOD WE 4717 03:51:23,961 --> 03:51:26,397 WERE AWARDED THIS GRANT TO MOVE 4718 03:51:26,397 --> 03:51:27,698 AHEAD, AND I'M GOING TO GIVE YOU 4719 03:51:27,698 --> 03:51:29,466 AN OVERVIEW WHAT THE STUDY IS 4720 03:51:29,466 --> 03:51:31,769 ABOUT AND THEN MOVE INTO WHAT 4721 03:51:31,769 --> 03:51:34,171 THE INTEROCEPTION ASPECT IS IN A 4722 03:51:34,171 --> 03:51:35,005 SECOND. 4723 03:51:35,005 --> 03:51:36,407 SO BASICALLY, RIGHT NOW THESE 4724 03:51:36,407 --> 03:51:38,175 RIM PLANTED FOR 4725 03:51:38,175 --> 03:51:38,943 TREATMENT-RESISTANT DEPRESSION 4726 03:51:38,943 --> 03:51:44,281 AND DRUG-RESISTANT EPILEPSY IN 4727 03:51:44,281 --> 03:51:46,717 PATIENTS, AND THE IDEA IS WE'LL 4728 03:51:46,717 --> 03:51:48,118 HAVE 144 PARTICIPANTS WITH LEFT 4729 03:51:48,118 --> 03:51:49,653 VAGUS NERVE IMPLANTEDDED, WHICH 4730 03:51:49,653 --> 03:51:51,956 IS WHERE IT'S IMPLANTED FOR 4731 03:51:51,956 --> 03:51:54,591 DEPRESSION AND EPILEPSY, 96 OF 4732 03:51:54,591 --> 03:51:56,327 THOSE NEWLY IMPLANTED AND 4733 03:51:56,327 --> 03:51:57,528 REMAINDER WOULD BE PREVIOUSLY 4734 03:51:57,528 --> 03:51:57,895 IMPLANTED. 4735 03:51:57,895 --> 03:52:00,931 THE IDEA IS TO MEASURE 4736 03:52:00,931 --> 03:52:03,434 PHYSIOLOGIC RESPONSES TO VAGAL 4737 03:52:03,434 --> 03:52:03,734 STIMULATION. 4738 03:52:03,734 --> 03:52:05,002 THIS IS THE THING, NOBODY HAS 4739 03:52:05,002 --> 03:52:06,303 MEASURED IN HUMANS WHAT IT'S 4740 03:52:06,303 --> 03:52:07,805 DOING TO THE BODY'S SYSTEMS EVEN 4741 03:52:07,805 --> 03:52:08,906 THOUGH WE ARE DOING THINGS ON 4742 03:52:08,906 --> 03:52:11,208 THE BRAIN, NOT TO THE BODY. 4743 03:52:11,208 --> 03:52:14,044 SO IN THIS CONSTITUTED CAN I 4744 03:52:14,044 --> 03:52:20,084 WE'LL -- IN THIS STUDY WE'LL 4745 03:52:20,084 --> 03:52:21,618 MEASURE WILL MRS. RESPONSES TO 4746 03:52:21,618 --> 03:52:26,090 HUMANS H HAD VAGAL NERVE 4747 03:52:26,090 --> 03:52:28,192 STIMULATION WILL CHANGE 4748 03:52:28,192 --> 03:52:29,827 AUTONOMIC NERVOUS SYSTEM ON THE 4749 03:52:29,827 --> 03:52:32,229 TOP, IMPACTS OTHER SYSTEMS, 4750 03:52:32,229 --> 03:52:33,864 IMMUNE, CARDIOVASCULAR, 4751 03:52:33,864 --> 03:52:34,965 METABOLIC, WE'LL LOOK AT 4752 03:52:34,965 --> 03:52:35,933 SHORT-TERM RESPONSES AND 4753 03:52:35,933 --> 03:52:38,035 LONG-TERM RESPONSES. 4754 03:52:38,035 --> 03:52:39,670 THERE'S SOME ANCILLARY PROJECTS 4755 03:52:39,670 --> 03:52:41,839 WHICH I WON'T HAVE TIME TO GET 4756 03:52:41,839 --> 03:52:42,306 INTO. 4757 03:52:42,306 --> 03:52:43,240 SO UNIVERSITY OF MINNESOTA IS 4758 03:52:43,240 --> 03:52:46,010 THE BASE FOR THSM THE CLINICAL 4759 03:52:46,010 --> 03:52:47,544 CO-DIRECTORS, Z I AD I ALREADY 4760 03:52:47,544 --> 03:52:50,180 MENTIONED AND HUBERT LIM AND TOM 4761 03:52:50,180 --> 03:52:55,586 HENRY WHO IS AN EPILEPTOLOGIST 4762 03:52:55,586 --> 03:52:57,721 RUN THE CLINICAL CORE, ALSO SIX 4763 03:52:57,721 --> 03:52:59,189 PARTNER SITES TO DO THIS STUDY 4764 03:52:59,189 --> 03:53:00,157 SHOWN HERE. 4765 03:53:00,157 --> 03:53:01,592 MEDICAL UNIVERSITY OF SOUTH 4766 03:53:01,592 --> 03:53:03,660 CAROLINA WITH MARK GEORGE, HIM 4767 03:53:03,660 --> 03:53:06,497 AND ZI AD DID VIRS I AM 4768 03:53:06,497 --> 03:53:09,566 PLABILITY FOR DEPRESSION, NOLAN 4769 03:53:09,566 --> 03:53:12,403 WILLIAMS, CHUCK CONWAY, TERRY 4770 03:53:12,403 --> 03:53:16,140 O'BRIEN AND VAUGHAN, MAYO CLINIC 4771 03:53:16,140 --> 03:53:18,108 90 MILES DOWN THE ROAD FROM US 4772 03:53:18,108 --> 03:53:23,147 WITH GLEG AND SARA AND 4773 03:53:23,147 --> 03:53:25,649 SHEPPARD PRATT IN BALTIMORE FOR 4774 03:53:25,649 --> 03:53:26,750 TREATING DEPRESSION. 4775 03:53:26,750 --> 03:53:27,484 SEVEN SITES. 4776 03:53:27,484 --> 03:53:28,385 I'LL SUMMARIZE BRIEFLY WHAT 4777 03:53:28,385 --> 03:53:29,787 WE'RE GOING TO DO IN THESE 4778 03:53:29,787 --> 03:53:31,455 SUBJECTS, IF YOU LOOK AT THE 4779 03:53:31,455 --> 03:53:34,425 TOP, COMMON STUDY PROTOCOLS, 4780 03:53:34,425 --> 03:53:35,259 CSP, THESE WOULD BE SUBJECTS 4781 03:53:35,259 --> 03:53:37,261 THAT ARE ALREADY IMPLANTED FOR 4782 03:53:37,261 --> 03:53:38,896 JUST SIMPLICITY, OKAY? 4783 03:53:38,896 --> 03:53:41,532 ONCE THEY'RE CONSENTED, THE 4784 03:53:41,532 --> 03:53:43,033 DEVICE, SO THE DEVICE HAS BEEN 4785 03:53:43,033 --> 03:53:45,035 ON, IT'S TURNED OFF FOR TWO TO 4786 03:53:45,035 --> 03:53:46,336 THREE WEEKS, WHICH IS SAFE 4787 03:53:46,336 --> 03:53:48,172 BECAUSE IT TAKES A LONG TIME TO 4788 03:53:48,172 --> 03:53:49,506 BE EFFECTIVE, IT TAKES A LONG 4789 03:53:49,506 --> 03:53:50,607 TIME TO WEAR OFF. 4790 03:53:50,607 --> 03:53:52,543 SO WE'LL GET A BASELINE AND THEN 4791 03:53:52,543 --> 03:53:56,046 THEY HAVE 24-HOUR AMBULATORY 4792 03:53:56,046 --> 03:53:57,481 BLOOD PRESSURE AND ECG, THEN 4793 03:53:57,481 --> 03:53:59,016 THEY COME TO ONE OF THREE SITES 4794 03:53:59,016 --> 03:54:01,218 THAT I'LL TALK ABOUT FOR STUDY 4795 03:54:01,218 --> 03:54:01,718 VISIT ONE. 4796 03:54:01,718 --> 03:54:02,853 THIS IS THE DAY WHERE THEY COME 4797 03:54:02,853 --> 03:54:04,721 IN TO MEASURE ACUTE RESPONSES TO 4798 03:54:04,721 --> 03:54:08,225 VAGAL NERVE STIMULATION IN THE 4799 03:54:08,225 --> 03:54:08,459 CLINIC. 4800 03:54:08,459 --> 03:54:10,527 THEN THEY WILL HAVE THE DEVICE 4801 03:54:10,527 --> 03:54:12,729 SET AT A RANDOMIZED SETTING G 4802 03:54:12,729 --> 03:54:14,031 AWAY FOR THREE MONTHS, COME BACK 4803 03:54:14,031 --> 03:54:15,999 AND DO IT AGAIN, AND THAT'S 4804 03:54:15,999 --> 03:54:17,000 STUDY VISIT TWO. 4805 03:54:17,000 --> 03:54:17,301 OKAY? 4806 03:54:17,301 --> 03:54:19,570 SO ACUTE AND CHRONIC RESPONSES. 4807 03:54:19,570 --> 03:54:21,238 THE BOTTOM ARE NEWLY IMPLANTED 4808 03:54:21,238 --> 03:54:24,675 BUT IT'S BASIC THE SAME STUDY 4809 03:54:24,675 --> 03:54:25,209 DESIGN. 4810 03:54:25,209 --> 03:54:26,844 SO WHAT DO THESE STUDY VISIT 4811 03:54:26,844 --> 03:54:28,178 LOOK LIKE? 4812 03:54:28,178 --> 03:54:29,580 THESE ARE, WE HAVE THREE SITES 4813 03:54:29,580 --> 03:54:31,682 THAT ARE DOING THESE ACUTE 4814 03:54:31,682 --> 03:54:33,050 STUDIES IN THE LABORATORY. 4815 03:54:33,050 --> 03:54:38,355 UNIVERSITY OF MINNESOTA, MONASH 4816 03:54:38,355 --> 03:54:40,991 AND MAYO CLINIC. 4817 03:54:40,991 --> 03:54:45,896 ONE DAY, VAUGHAN CAME IN, WORKED 4818 03:54:45,896 --> 03:54:51,935 OUT THE PROTOCOL WITH SARA -- 4819 03:54:51,935 --> 03:54:54,037 AND THEY'RE SHOWN MEASURING THE 4820 03:54:54,037 --> 03:54:55,572 SUBJECT, MEASURING VARIABLES 4821 03:54:55,572 --> 03:54:57,074 DURING VAGAL STIMULATION. 4822 03:54:57,074 --> 03:54:58,742 WE'RE MEASURING ONE OF THE KEY 4823 03:54:58,742 --> 03:55:00,444 VARIABLES IS MUSCLE SYMPATHETIC 4824 03:55:00,444 --> 03:55:01,178 NERVE ACTIVITY. 4825 03:55:01,178 --> 03:55:03,747 IF I DW BACK, YOU SEE AN 4826 03:55:03,747 --> 03:55:04,848 ELECTROPLACED IN THE PERONEAL 4827 03:55:04,848 --> 03:55:07,384 NERVE, BASE OF THE KNEE THERE, 4828 03:55:07,384 --> 03:55:09,653 ON THE TOP YOU SEE ECG, BLOOD 4829 03:55:09,653 --> 03:55:11,855 PRESSURE, RESPIRATION AND THAT 4830 03:55:11,855 --> 03:55:14,057 BLUE IS MUSCLE SYMPATHETIC NERVE 4831 03:55:14,057 --> 03:55:15,025 ACTIVITY DIRECT MEASUREMENT IN 4832 03:55:15,025 --> 03:55:15,225 HUMAN. 4833 03:55:15,225 --> 03:55:17,127 THE REASON THIS IS IMPORTANT IS 4834 03:55:17,127 --> 03:55:19,296 IF THAT RESPONDS IN ANY WAY TO 4835 03:55:19,296 --> 03:55:20,697 VAGAL STIMULATION, THAT MEANS 4836 03:55:20,697 --> 03:55:23,233 YOU STIMULATED THE AFER TOANS 4837 03:55:23,233 --> 03:55:28,071 THE BRAIN WHICH REFLEX ALLY 4838 03:55:28,071 --> 03:55:29,706 AFFECTS, THAT'S SYMPATHETIC 4839 03:55:29,706 --> 03:55:29,907 NERVE. 4840 03:55:29,907 --> 03:55:30,474 DIRECT MEASUREMENT. 4841 03:55:30,474 --> 03:55:32,009 WE KNOW IF IT RESPONDS, WE HAD 4842 03:55:32,009 --> 03:55:33,844 TO GO UP THROUGH THE REFLEX 4843 03:55:33,844 --> 03:55:34,945 PATHWAYS IN THE BRAIN TO GET A 4844 03:55:34,945 --> 03:55:35,212 RESPONSE. 4845 03:55:35,212 --> 03:55:39,783 SO THE PATIENT IS -- THE 4846 03:55:39,783 --> 03:55:40,617 PARTICIPANT IS INSTRUMENTED FOR 4847 03:55:40,617 --> 03:55:41,852 IS THAT, THIS IS THE MORNING OF 4848 03:55:41,852 --> 03:55:42,619 THE STUDY. 4849 03:55:42,619 --> 03:55:43,387 BASICALLY THEY'RE LAYING ON THE 4850 03:55:43,387 --> 03:55:45,455 TABLE, YOU MEASURE THE RESPONSE 4851 03:55:45,455 --> 03:55:46,557 OF BASAL BLOOD PRESSURE, HEART 4852 03:55:46,557 --> 03:55:49,526 RATE, ECG, SYMPATHETIC ACTIVITY 4853 03:55:49,526 --> 03:55:52,462 TO DIFFERENT STIMULUS 4854 03:55:52,462 --> 03:55:52,930 PARAMETERS. 4855 03:55:52,930 --> 03:55:54,231 THREE SETTINGS, IN BETWEEN THOSE 4856 03:55:54,231 --> 03:55:57,167 YOU GET A BLOOD SAMPLE, AND THEN 4857 03:55:57,167 --> 03:55:59,703 THE LAST PART SAYS CHRONIC 4858 03:55:59,703 --> 03:56:01,872 SETTING ANS REFLEX TESTING, WE 4859 03:56:01,872 --> 03:56:05,042 DO SOME REFLEXES TO ENGAGE THE 4860 03:56:05,042 --> 03:56:06,343 AUTONOMIC NERVE SYSTEM AND SEE 4861 03:56:06,343 --> 03:56:08,779 WHAT VAGAL NERVE STIM 4862 03:56:08,779 --> 03:56:10,647 STIMULATION DOES TO THAT AND 4863 03:56:10,647 --> 03:56:13,150 THERE'S AN ECHOCARDIOGRAPHY DONE 4864 03:56:13,150 --> 03:56:14,017 IN THE AFTERNOON. 4865 03:56:14,017 --> 03:56:16,853 REFLEX TESTING, TILT TABLE TEST, 4866 03:56:16,853 --> 03:56:18,956 COMMON AM DONE WHEN YOU GO 4867 03:56:18,956 --> 03:56:21,024 FROM -- COMMONLY DONE WHEN YOU 4868 03:56:21,024 --> 03:56:23,327 GO FROM SUPINE TO UPRATE, 4869 03:56:23,327 --> 03:56:25,162 ACTIVATE THE VAGAL NERVOUS 4870 03:56:25,162 --> 03:56:25,629 SYSTEM. 4871 03:56:25,629 --> 03:56:26,730 COUPLE OTHERS AS WELL. 4872 03:56:26,730 --> 03:56:28,365 I'LL GET TO INTEROCEPTION PRETTY 4873 03:56:28,365 --> 03:56:28,899 QUICK HERE. 4874 03:56:28,899 --> 03:56:30,334 JUST TO MENTION THE DATA 4875 03:56:30,334 --> 03:56:31,635 ANALYSIS THAT'S SHOWN HERE, WE 4876 03:56:31,635 --> 03:56:34,371 HAVE FOUR SYSTEMS WE'RE 4877 03:56:34,371 --> 03:56:35,906 STUDYING, AUTONOMIC NICK ON THE 4878 03:56:35,906 --> 03:56:37,975 LEFT, CARDIOVASCULAR, IMMUNE AND 4879 03:56:37,975 --> 03:56:38,242 METABOLIC. 4880 03:56:38,242 --> 03:56:40,277 FIRST LAYER IS THE 4881 03:56:40,277 --> 03:56:41,144 STRAIGHTFORWARD THINGS YOU WOULD 4882 03:56:41,144 --> 03:56:42,913 MEASURE IN A SUBJECT. 4883 03:56:42,913 --> 03:56:45,349 BLOOVMENT MUSCLE SAME PATHETIC 4884 03:56:45,349 --> 03:56:46,016 NERVE ACTIVITY. 4885 03:56:46,016 --> 03:56:47,818 HEART RATE. 4886 03:56:47,818 --> 03:56:49,253 IMMUNE SYSTEM STANDARD CYTOKINE 4887 03:56:49,253 --> 03:56:50,787 PANEL FOR EXAMPLE. 4888 03:56:50,787 --> 03:56:53,523 METABOLIC, HEE GLOW BIN A1C. 4889 03:56:53,523 --> 03:56:55,392 THEN WE GO DOWN TO DIFFERENT 4890 03:56:55,392 --> 03:56:57,027 LAYERS WHICH ARE MUCH MORE 4891 03:56:57,027 --> 03:56:57,861 COMPLICATED ANALYSIS. 4892 03:56:57,861 --> 03:56:59,529 FOR EXAMPLE, WITH METABOLIC WE 4893 03:56:59,529 --> 03:57:02,266 GET INTO METABOLOMICS, WE GET 4894 03:57:02,266 --> 03:57:04,501 INTO ALL THE OMICS. 4895 03:57:04,501 --> 03:57:05,802 FOR IMMUNE SYSTEM AND METABOLIC 4896 03:57:05,802 --> 03:57:07,337 SYSTEM SO WE CAN LOOK AT HOW 4897 03:57:07,337 --> 03:57:08,739 THESE VARIABLES RESPOND. 4898 03:57:08,739 --> 03:57:10,040 AND THEN JUST TO MAKE THAT 4899 03:57:10,040 --> 03:57:12,242 POINT, THOSE ARE DONE THROUGH 4900 03:57:12,242 --> 03:57:13,410 THE BLOOD SAMPLING WE GET AND 4901 03:57:13,410 --> 03:57:14,878 THESE ARE THE INVESTIGATORS AT 4902 03:57:14,878 --> 03:57:16,513 MINNESOTA THAT RUN THE IMMUNE 4903 03:57:16,513 --> 03:57:19,349 SYSTEM AS ASSAYS AND THEN -- 4904 03:57:19,349 --> 03:57:20,984 ASSAYS AND THEN PETER CRAWFORD 4905 03:57:20,984 --> 03:57:21,885 DOING THE METABOLIC SYSTEM. 4906 03:57:21,885 --> 03:57:23,620 THAT'S THE STUDY, WE'RE ABOUT TO 4907 03:57:23,620 --> 03:57:25,689 ENROLL THE FIRST PARTICIPANT. 4908 03:57:25,689 --> 03:57:27,357 WE'RE INTO YEAR ONE, WE'RE ABOUT 4909 03:57:27,357 --> 03:57:28,458 READY TO GET STARTED. 4910 03:57:28,458 --> 03:57:29,660 SO THAT'S WHY I SAID THIS IS 4911 03:57:29,660 --> 03:57:31,828 LIKE COMING TO TRACTION. 4912 03:57:31,828 --> 03:57:34,364 NOW WHAT ABOUT INTEROCEPTION? 4913 03:57:34,364 --> 03:57:36,767 SO ZI AD WHO IS HERE AND I'M UP 4914 03:57:36,767 --> 03:57:39,836 HERE SPEAKING FOR HIM, AS A 4915 03:57:39,836 --> 03:57:41,471 SUPPLEMENT FOR THIS STUDY, TO 4916 03:57:41,471 --> 03:57:46,943 LOOK AT THE EFFECTS OF VNS ON 4917 03:57:46,943 --> 03:57:49,246 CENTRAL AUTONOMIC NETWORK AND 4918 03:57:49,246 --> 03:57:50,013 INTEROCEPTION, HOW GREAT WOULD 4919 03:57:50,013 --> 03:57:51,648 IT BE IN THE SAME SUBJECT TO 4920 03:57:51,648 --> 03:57:52,316 MEASURE WHAT'S HAPPENING IN THE 4921 03:57:52,316 --> 03:57:53,850 BODY AND WHAT'S HAPPENING IN THE 4922 03:57:53,850 --> 03:57:55,252 BRAIN, PUT IT ALL TOGETHER AS WE 4923 03:57:55,252 --> 03:57:56,019 TALKED ABOUT THIS MORNING THAT 4924 03:57:56,019 --> 03:57:57,454 WOULD BE IDEALLY WHAT WOULD 4925 03:57:57,454 --> 03:57:57,788 HAPPEN. 4926 03:57:57,788 --> 03:58:00,957 THIS NICE DIAGRAM HERE OF THE 4927 03:58:00,957 --> 03:58:03,593 ENTEROSEPTION NETWORK FROM 4928 03:58:03,593 --> 03:58:05,629 REVIEW BY LANG I PUTTER UP HERE 4929 03:58:05,629 --> 03:58:06,396 TO MAKE NOINLT. 4930 03:58:06,396 --> 03:58:09,466 AS YOU ALL KNOW, THE VAGUS NERVE 4931 03:58:09,466 --> 03:58:11,668 IS 80% AFFERENT FIBERS TO THE 4932 03:58:11,668 --> 03:58:14,404 BRAIN 20RBGS% OUT TO THE BODY. 4933 03:58:14,404 --> 03:58:15,806 -- 20% OUT TO THE BODY. SO IF 4934 03:58:15,806 --> 03:58:17,808 YOU HAVE AN ELECTRODE ON YOUR 4935 03:58:17,808 --> 03:58:19,676 VAGUS NERVE YOU'RE OBVIOUSLY 4936 03:58:19,676 --> 03:58:22,312 ACTIVATING A LOT OF AFFERENT 4937 03:58:22,312 --> 03:58:24,147 ACTIVITY TO THE BRAIN, USED FOR 4938 03:58:24,147 --> 03:58:26,350 ADDICTION SHES EPILEPSY, OTHER 4939 03:58:26,350 --> 03:58:28,085 THINGS, ALSO GOING OUT TO THE 4940 03:58:28,085 --> 03:58:28,518 ORGANS. 4941 03:58:28,518 --> 03:58:29,720 PART OF THE STHING TO DO BOTH. 4942 03:58:29,720 --> 03:58:32,589 THE IDEA SO DO BRAIN IMAGING AND 4943 03:58:32,589 --> 03:58:33,890 LOOK WHAT'S HAPPENING, I'LL GO 4944 03:58:33,890 --> 03:58:35,325 INTO THAT FOR A LITTLE BIT. 4945 03:58:35,325 --> 03:58:37,928 SO THIS IS A PAPER OF ZI -- THIS 4946 03:58:37,928 --> 03:58:42,733 IS A PAPER OF ZIAD FROM 2007, 4947 03:58:42,733 --> 03:58:44,401 FMRI IN PARTICIPANTS DURING 4948 03:58:44,401 --> 03:58:45,502 VAGAL NERVE STIMULATION. 4949 03:58:45,502 --> 03:58:47,904 ON THE RIGHT YOU SEE SHOWING 4950 03:58:47,904 --> 03:58:52,042 RESPONSES IN THE INSULA, AND 4951 03:58:52,042 --> 03:58:53,910 THAT IS THE CORRELATION AND I'LL 4952 03:58:53,910 --> 03:58:55,779 SHOW THAT IN A MINUTE, THE 4953 03:58:55,779 --> 03:58:57,314 ACTIVATION OF THAT AREA 4954 03:58:57,314 --> 03:58:59,716 CORRESPONDS TO THE RATING FOR 4955 03:58:59,716 --> 03:59:02,219 DEPRESSION FOR THAT PARTICULAR 4956 03:59:02,219 --> 03:59:02,619 PARTICIPANT. 4957 03:59:02,619 --> 03:59:05,622 BOTTOM RIGHT IS SOMATOSENSORY 4958 03:59:05,622 --> 03:59:06,723 CORTEX SHOWING IT CREASES HE 4959 03:59:06,723 --> 03:59:08,892 WITH INTENSITY, WHICH SHOWS YOU 4960 03:59:08,892 --> 03:59:11,728 IT'S AN INTERNAL CONTROL. 4961 03:59:11,728 --> 03:59:11,995 INCREASES. 4962 03:59:11,995 --> 03:59:14,064 ON THE LEFT IS THAT THESE 4963 03:59:14,064 --> 03:59:16,466 RESPONSES DECREASE OVER TIME. 4964 03:59:16,466 --> 03:59:18,201 SO THAT WAS 2007. 4965 03:59:18,201 --> 03:59:20,437 AND THIS IS DATA FROM THAT PAPER 4966 03:59:20,437 --> 03:59:20,637 AGAIN. 4967 03:59:20,637 --> 03:59:22,472 SO WHAT I WANT YOU TO SEE ON THE 4968 03:59:22,472 --> 03:59:24,374 RIGHT-HAND SIDE FOR THE RIGHT 4969 03:59:24,374 --> 03:59:26,676 INSULA BEGINNING AT WEEK ZERO 4970 03:59:26,676 --> 03:59:28,078 AFTER IMPLANTATION THE INITIAL 4971 03:59:28,078 --> 03:59:29,413 RESPONSE IS ACTIVATION OF THE 4972 03:59:29,413 --> 03:59:31,915 RIGHT INSULA. 4973 03:59:31,915 --> 03:59:34,317 YOU GO OUT TO 120 WEEKS. 4974 03:59:34,317 --> 03:59:36,853 WHEN YOU GET OUT TO ABOUT 32, 4975 03:59:36,853 --> 03:59:38,688 33, ABOUT EIGHT MONTHS, YOU GO 4976 03:59:38,688 --> 03:59:40,257 FROM ACTIVATE THAT GO TO 4977 03:59:40,257 --> 03:59:41,558 DEACTIVATING IT, SO OVER TIME 4978 03:59:41,558 --> 03:59:42,993 YOU SEE GOING FROM ACTIVATION 4979 03:59:42,993 --> 03:59:44,494 GOING TO DEACTIVATION. 4980 03:59:44,494 --> 03:59:46,263 SAME THING IN THE RIGHT MIDDLE 4981 03:59:46,263 --> 03:59:51,067 FRONTAL CORTEX. 4982 03:59:51,067 --> 03:59:52,269 SHOWS CORRELATION BETWEEN 4983 03:59:52,269 --> 03:59:54,037 HAMILTON DEPRESSION RATING SCORE 4984 03:59:54,037 --> 03:59:55,772 AND THAT ACTIVATION AND THE 4985 03:59:55,772 --> 03:59:58,842 SPOINT YOU SEE THAT GOING TO THE 4986 03:59:58,842 --> 04:00:01,378 LEFT WOULD BE LESS DEPRESSION 4987 04:00:01,378 --> 04:00:02,913 CORRELATED TO THAT LESS 4988 04:00:02,913 --> 04:00:03,413 ACTIVATION. 4989 04:00:03,413 --> 04:00:05,081 SO IN OTHER WORDS, THOSE PRAP ON 4990 04:00:05,081 --> 04:00:06,950 THE BOTTOM INDICATE OVER TIME 4991 04:00:06,950 --> 04:00:08,385 YOU'RE TREEG THE DEPRESSION BY 4992 04:00:08,385 --> 04:00:10,220 SEEING THESE TIME-DEPENDENT 4993 04:00:10,220 --> 04:00:12,088 CHANGES IN THIS REGION. 4994 04:00:12,088 --> 04:00:16,493 SO THAT WAS 2007. 4995 04:00:16,493 --> 04:00:18,462 SO NOW WHAT THE GOAL IS WITH THE 4996 04:00:18,462 --> 04:00:20,197 SUPPLEMENT THAT ZI AD IS GOING 4997 04:00:20,197 --> 04:00:22,065 TO RUN IN SOME OF THESE 4998 04:00:22,065 --> 04:00:24,034 PARTICIPANTS OF OUR STUDY IS TO 4999 04:00:24,034 --> 04:00:27,604 FIRST LOOK AT THE EFFECTS OF VNS 5000 04:00:27,604 --> 04:00:29,940 ON THE INTEROCEPTION NETWORK 5001 04:00:29,940 --> 04:00:32,242 USING RELATED VNS MRI SO BEING 5002 04:00:32,242 --> 04:00:33,376 ABLE TO LOOK AT WHAT'S HAPPENING 5003 04:00:33,376 --> 04:00:34,678 IN THE BRAIN WHILE THE DEVICE IS 5004 04:00:34,678 --> 04:00:37,247 ON, THAT'S NUMBER ONE. 5005 04:00:37,247 --> 04:00:40,450 THE SECOND TO LOOK HOW CHRONIC 5006 04:00:40,450 --> 04:00:41,785 VNS CHANGES THE DYNAMIC CHANGES 5007 04:00:41,785 --> 04:00:43,753 IN A LARGE-SCALE IN THE 5008 04:00:43,753 --> 04:00:44,721 FUNCTIONAL NETWORK AND HOW 5009 04:00:44,721 --> 04:00:46,590 THAT'S CORRELATED TO THESE 5010 04:00:46,590 --> 04:00:49,326 CHANGES IN AUTO NICK AND 5011 04:00:49,326 --> 04:00:50,494 CARDIOVASCULAR -- AUTONOMIC AND 5012 04:00:50,494 --> 04:00:51,261 CARDIOVASCULAR ACTIVITY WE 5013 04:00:51,261 --> 04:00:53,263 TALKED ABOUT. SO BASIC IS 5014 04:00:53,263 --> 04:00:54,798 PROACH IS -- BASIC APPROACH IS 5015 04:00:54,798 --> 04:00:56,766 SHOWN HERE, PROTOCOL I 140ED 5016 04:00:56,766 --> 04:00:58,301 EARLY EARLIER BUT ON THE LEFT IN 5017 04:00:58,301 --> 04:01:00,804 THE RED WE'LL GET A RESTING 5018 04:01:00,804 --> 04:01:03,006 STATE FMRI BEFORE THE DEVICE 5019 04:01:03,006 --> 04:01:04,875 GOES IN, THEY GO THROUGH THE 5020 04:01:04,875 --> 04:01:06,176 PROTOCOL WE'RE RUNNING AND YOU 5021 04:01:06,176 --> 04:01:07,911 GET TO THAT STUDY VISIT ONE 5022 04:01:07,911 --> 04:01:10,313 WE'LL DO BRAIN IMAGING IN THEM 5023 04:01:10,313 --> 04:01:15,018 AND THEN LOOK AT THE FMRI AS 5024 04:01:15,018 --> 04:01:16,987 WELL TO LOOK AT WHAT'S HAPPENING 5025 04:01:16,987 --> 04:01:18,622 IN VNS IN THE MOMENT. 5026 04:01:18,622 --> 04:01:20,090 THEY COME BACK AFTER A FEW WEEKS 5027 04:01:20,090 --> 04:01:21,825 AND WE DO THAT AGAIN AND GET 5028 04:01:21,825 --> 04:01:24,127 ANOTHER RESTING STATE FMRI. 5029 04:01:24,127 --> 04:01:26,763 SO IN 25 PARTICIPANTS OUT OF 5030 04:01:26,763 --> 04:01:28,498 THIS 144, THE GOAL IS TO DO 5031 04:01:28,498 --> 04:01:29,833 SIMULTANEOUS BRAIN IMAGING AND 5032 04:01:29,833 --> 04:01:30,901 MEASURING THESE OTHER RESPONSES 5033 04:01:30,901 --> 04:01:33,870 SO WE CAN LOOK AT NOT ONLY 5034 04:01:33,870 --> 04:01:34,538 AUTONOMIC, WHICH IS OBVIOUSLY 5035 04:01:34,538 --> 04:01:36,840 GOING TO CHANGE, BUT THE 5036 04:01:36,840 --> 04:01:39,543 ENTEROACCEPTTIVE NETWORK AS 5037 04:01:39,543 --> 04:01:39,776 WELL. 5038 04:01:39,776 --> 04:01:41,278 SO THAT'S THE OVERALL GOAL. 5039 04:01:41,278 --> 04:01:42,412 SO I THINK THE IDEA OF THE 5040 04:01:42,412 --> 04:01:43,947 PRESENTATION HERE IS TO LET THE 5041 04:01:43,947 --> 04:01:45,015 COMMUNITY KNOW THAT WE'RE ABOUT 5042 04:01:45,015 --> 04:01:46,550 TO EMBARK ON THIS STUDY, WHICH 5043 04:01:46,550 --> 04:01:51,821 IS VERY EXCITING SO STAY TUNED 5044 04:01:51,821 --> 04:01:56,660 FOR RESULTS FROM THAT. 5045 04:01:56,660 --> 04:01:58,929 THIS IS A LARGE, GLOBAL STUDY. 5046 04:01:58,929 --> 04:01:59,829 WE'RE ABOUT TO START. 5047 04:01:59,829 --> 04:02:01,898 WE HAVE TWO YEARS TO DO THIS. 5048 04:02:01,898 --> 04:02:03,433 SO STAY TUNED AND WE'LL COME 5049 04:02:03,433 --> 04:02:07,837 BACK HOPEFULLY WITH THE RESULTS 5050 04:02:07,837 --> 04:02:09,205 TO COME. 5051 04:02:09,205 --> 04:02:15,478 THANK YOU. 5052 04:02:15,478 --> 04:02:19,182 >> THANK YOU, JOHN. 5053 04:02:19,182 --> 04:02:19,516 QUESTION? 5054 04:02:19,516 --> 04:02:21,251 >> GREAT TALK. 5055 04:02:21,251 --> 04:02:23,353 I'M FROM THE UNIVERSITY OF SOUTH 5056 04:02:23,353 --> 04:02:23,620 FLORIDA. 5057 04:02:23,620 --> 04:02:26,089 SO WHAT I WANTED TO ASK IS, YOU 5058 04:02:26,089 --> 04:02:28,058 KNOW, FOR SOME OF US WHO HAVE 5059 04:02:28,058 --> 04:02:29,659 STUDIED VAGAL NEUROPHYSIOLOGY 5060 04:02:29,659 --> 04:02:32,462 FOR SOME TIME, WE'RE ASTONISHED 5061 04:02:32,462 --> 04:02:34,264 BY VAGAL NERVE STIMULATION 5062 04:02:34,264 --> 04:02:35,865 DOESN'T DO THE THINGS WE THINK 5063 04:02:35,865 --> 04:02:37,067 IT SHOULD DO. 5064 04:02:37,067 --> 04:02:39,603 SO IN TERMS OF, ARE YOU GOING TO 5065 04:02:39,603 --> 04:02:42,639 ASK THE PARTICIPATE WHANTS THEY 5066 04:02:42,639 --> 04:02:43,740 FEEL -- PARTICIPANTS WHAT THEY 5067 04:02:43,740 --> 04:02:44,608 FEEL AS WELL? 5068 04:02:44,608 --> 04:02:48,445 LIKE DO THEY FEEL SCRATCHY, 5069 04:02:48,445 --> 04:02:49,179 COUGHY, FULL? 5070 04:02:49,179 --> 04:02:51,915 YOU KNOW, ORGAN SENSATION? 5071 04:02:51,915 --> 04:02:54,117 ARE YOU GOING TO DO THAT? 5072 04:02:54,117 --> 04:02:56,219 >> DURING THE ACUTE 5073 04:02:56,219 --> 04:02:56,553 MEASUREMENTS? 5074 04:02:56,553 --> 04:02:57,988 >> THE THE THREE MONTHS, 5075 04:02:57,988 --> 04:02:58,254 OBVIOUSLY. 5076 04:02:58,254 --> 04:02:58,855 >> SURE. 5077 04:02:58,855 --> 04:03:00,490 YES, WE ARE. 5078 04:03:00,490 --> 04:03:02,125 YEAH, I FORGOT TO MENTION AS 5079 04:03:02,125 --> 04:03:03,460 WELL, AND I APPRECIATE, ONE OF 5080 04:03:03,460 --> 04:03:06,096 THE ANCILLARY STUDIES VAUGHN 5081 04:03:06,096 --> 04:03:07,831 MACEFIELD IS GOING TO MEASURE 5082 04:03:07,831 --> 04:03:09,232 DIRECTLY FROM THE VAGUS NERVE 5083 04:03:09,232 --> 04:03:11,201 DURING THE VAGAL NERVE 5084 04:03:11,201 --> 04:03:12,869 STIMULATION TO CHARACTERIZE 5085 04:03:12,869 --> 04:03:14,070 DIFFERENT FIBER TYPES, THOSE 5086 04:03:14,070 --> 04:03:14,938 KINDS OF THINGS. 5087 04:03:14,938 --> 04:03:16,473 BUT TO WHAT YOU'RE SAYING, THAT 5088 04:03:16,473 --> 04:03:18,441 WILL OBVIOUSLY COME UP, RIGHT, 5089 04:03:18,441 --> 04:03:20,543 DURING THE ACUTE. 5090 04:03:20,543 --> 04:03:22,078 BUT KEEP IN MIND THAT THE COMMON 5091 04:03:22,078 --> 04:03:23,913 STUDY PROTOCOL ARE THE CLINICAL 5092 04:03:23,913 --> 04:03:25,882 PARAMETERS THAT ARE TYPICALLY 5093 04:03:25,882 --> 04:03:26,449 USED, RIGHT? 5094 04:03:26,449 --> 04:03:28,418 SO I MEAN, THAT'S OUT THERE 5095 04:03:28,418 --> 04:03:29,285 ALREADY, I'M SURE. 5096 04:03:29,285 --> 04:03:30,820 BUT WE CAN LOOK INTO THAT 5097 04:03:30,820 --> 04:03:31,054 DETAIL. 5098 04:03:31,054 --> 04:03:31,588 >> THANKS. 5099 04:03:31,588 --> 04:03:35,191 >> YEAH. 5100 04:03:35,191 --> 04:03:41,631 >> THANKS VERY MUCH, JOHN. 5101 04:03:41,631 --> 04:03:52,008 NEXT UP IS RUI CHANG. 5102 04:03:52,475 --> 04:03:56,279 >> FIRST I WANT TO THANK THE 5103 04:03:56,279 --> 04:03:57,647 WHOLE COMMITTEE FOR THIS 5104 04:03:57,647 --> 04:03:59,449 FANTASTIC MEETING, IT'S AMAZING, 5105 04:03:59,449 --> 04:04:01,351 AND ALSO FOR GIVING ME THIS 5106 04:04:01,351 --> 04:04:02,652 WONDERFUL OPPORTUNITY TO PRESENT 5107 04:04:02,652 --> 04:04:03,987 OUR RESEARCH AMONG SO MANY 5108 04:04:03,987 --> 04:04:04,854 GIANTS IN THE FIELD. 5109 04:04:04,854 --> 04:04:08,591 I REALLY FEEL LIKE VERY EXCITED. 5110 04:04:08,591 --> 04:04:11,294 SO MY LAB IS INTERESTED IN THE 5111 04:04:11,294 --> 04:04:13,163 INTERACTIONS BETWEEN THE 5112 04:04:13,163 --> 04:04:16,032 VISCERAL ORGANS AND HOW THIS 5113 04:04:16,032 --> 04:04:17,333 INTERACTION REGULATES OUR 5114 04:04:17,333 --> 04:04:18,435 PHYSIOLOGY AND BEHAVIORS. 5115 04:04:18,435 --> 04:04:19,536 TODAY I'LL SHARE WITH YOU SOME 5116 04:04:19,536 --> 04:04:20,937 OF OUR RESULTS ABOUT THE CODING 5117 04:04:20,937 --> 04:04:25,542 LOWJ I CAN OF INTEROCEPTION 5118 04:04:25,542 --> 04:04:26,976 AND -- LODGE I GO. 5119 04:04:26,976 --> 04:04:28,511 USING MOUSE AS MODEL AND 5120 04:04:28,511 --> 04:04:29,913 HOPEFULLY OUR WORK IN THE BASIC 5121 04:04:29,913 --> 04:04:32,215 SCIENCE CAN BE TRANSLATED TO 5122 04:04:32,215 --> 04:04:39,689 HUMAN SOMEDAY NOT FAR RNTLE. 5123 04:04:39,689 --> 04:04:41,191 NOT FAR. 5124 04:04:41,191 --> 04:04:43,293 SO INTEROCEPTION IS CRITICAL FOR 5125 04:04:43,293 --> 04:04:44,761 OUR SURVIVAL AND WE ARE ACTUALLY 5126 04:04:44,761 --> 04:04:45,562 VERY GOOD AT THIS. 5127 04:04:45,562 --> 04:04:49,365 FOR EXAMPLE, WE CAN DETECT -- 5128 04:04:49,365 --> 04:04:52,702 EVERY SINGLY HEARTBEAT AND 5129 04:04:52,702 --> 04:04:55,638 PROVIDE -- FOR COLLEAGUES, WE 5130 04:04:55,638 --> 04:04:57,674 KNOW MEEZ YAITD BY THE CHANNELS. 5131 04:04:57,674 --> 04:05:00,243 WE CAN CONSTANTLY SENSE THESE 5132 04:05:00,243 --> 04:05:01,911 CONTENTS, OR INGESTED MATERIALS 5133 04:05:01,911 --> 04:05:03,713 LIKE NUTRIENTS AND TOXINS, AS 5134 04:05:03,713 --> 04:05:06,816 WELL AS RELEASE CHEMICALS LIKE 5135 04:05:06,816 --> 04:05:09,986 HORMONES AND SIGNALS, AND 5136 04:05:09,986 --> 04:05:11,621 SENSING THESE SIGNALS WILL HELP 5137 04:05:11,621 --> 04:05:15,558 US MAINTAIN PHYSIOLOGICAL 5138 04:05:15,558 --> 04:05:16,860 HOMOEOSTASIS, PROVIDE 5139 04:05:16,860 --> 04:05:17,761 MOTIVATIONAL -- AND EVEN SHAPE 5140 04:05:17,761 --> 04:05:18,895 OUR THOUGHTS AND EMOTIONS. 5141 04:05:18,895 --> 04:05:21,264 SO MANY OF THESE INTERNAL 5142 04:05:21,264 --> 04:05:22,232 VISCERAL ORGAN SIGNALS ARE 5143 04:05:22,232 --> 04:05:24,734 COMMUNICATED TO THE BRAIN VIA 5144 04:05:24,734 --> 04:05:27,203 THE VAGUS NERVE, WHICH IS A 5145 04:05:27,203 --> 04:05:29,839 MAJOR IN TERMS OF THE SYSTEM AND 5146 04:05:29,839 --> 04:05:32,342 CRITICAL BODY TO BRING ACCESS. 5147 04:05:32,342 --> 04:05:35,278 SO IN ADDITION TO IT'S VERY WELL 5148 04:05:35,278 --> 04:05:37,347 CHARACTERIZED AND KNOWN ROLE IN 5149 04:05:37,347 --> 04:05:38,448 THE PARASYMPATHETIC CONTROL OF 5150 04:05:38,448 --> 04:05:40,950 THE ORGANS, THE VAGUS NERVE ALSO 5151 04:05:40,950 --> 04:05:42,185 CONTAINS MANY SENSORY NEURONS 5152 04:05:42,185 --> 04:05:44,788 THAT PROVIDE EXTENSIVE 5153 04:05:44,788 --> 04:05:45,989 INNERVATION, THE MAJORITY OF THE 5154 04:05:45,989 --> 04:05:48,091 VISCERAL ORGANS INCLUDING THE 5155 04:05:48,091 --> 04:05:51,027 LUNG, HEART, STOMACH, INTESTINE, 5156 04:05:51,027 --> 04:05:53,530 LIVER, KIDNEY AND PANCREAS AND 5157 04:05:53,530 --> 04:05:56,499 MANY ORGANS EVEN NOT LISTED 5158 04:05:56,499 --> 04:05:57,133 HERE. 5159 04:05:57,133 --> 04:05:59,435 THESE SENSORY NEURONS CAN DETECT 5160 04:05:59,435 --> 04:06:00,737 NUMEROUS CHANGES WITHIN THE 5161 04:06:00,737 --> 04:06:02,939 VISCERAL ORGANS, AND THEY WILL 5162 04:06:02,939 --> 04:06:04,574 PRESENT THIS INFORMATION OUT TO 5163 04:06:04,574 --> 04:06:05,675 THE BRAIN. 5164 04:06:05,675 --> 04:06:06,976 SO NOW YOU CAN IMAGINE THAT 5165 04:06:06,976 --> 04:06:08,845 THESE NEURONS MUST BE VERY 5166 04:06:08,845 --> 04:06:11,381 COMPLEX AND HETEROGENEOUS, AND 5167 04:06:11,381 --> 04:06:13,116 INDEED, OVER THE PAST DECADE 5168 04:06:13,116 --> 04:06:14,684 ALSO, THERE ARE MANY, MANY 5169 04:06:14,684 --> 04:06:18,822 STUDIES FOCUSING ON THIS VERY 5170 04:06:18,822 --> 04:06:23,226 CRITICAL BODY-BRAIN AXIS AND HOW 5171 04:06:23,226 --> 04:06:24,727 THESE NEURONS CONTROL FUNCTIONS 5172 04:06:24,727 --> 04:06:26,396 IN THE RESPIRATORY, 5173 04:06:26,396 --> 04:06:28,264 CARDIOVASCULAR, DIGESTIVE, 5174 04:06:28,264 --> 04:06:30,667 METABOLIC, IMMUNE AND EVEN THE 5175 04:06:30,667 --> 04:06:31,401 COGNITIVE SYSTEMS. 5176 04:06:31,401 --> 04:06:35,605 AND RECENTLY, THIS NERVE IS ALSO 5177 04:06:35,605 --> 04:06:40,109 VERY HOT TOPIC FOR VERY MANY 5178 04:06:40,109 --> 04:06:41,411 NEUROLOGICAL DISORDERS INCLUDING 5179 04:06:41,411 --> 04:06:43,947 PEAS AS WE HEARD EARLIER THIS 5180 04:06:43,947 --> 04:06:45,582 DHAISH INCLUDING PARKINSON'S 5181 04:06:45,582 --> 04:06:47,984 DISEASE AS WE HEARD EARLIER THIS 5182 04:06:47,984 --> 04:06:49,519 MORNING. 5183 04:06:49,519 --> 04:06:51,588 RS STILL VERY LITTLE IS KNOWN 5184 04:06:51,588 --> 04:06:54,324 ABOUT HOW THIS NEW OWN AL 5185 04:06:54,324 --> 04:06:57,927 CAPACITY AND DIVERSITY ACTUALLY 5186 04:06:57,927 --> 04:06:59,596 FACILITATES INTEROCEPTION CODING 5187 04:06:59,596 --> 04:07:00,897 AT A SYSTEMS LEVEL. 5188 04:07:00,897 --> 04:07:03,099 SO WE KNOW THAT THESE NUMEROUS 5189 04:07:03,099 --> 04:07:05,034 BODY SIGNALS CAN BE VERY PRE 5190 04:07:05,034 --> 04:07:06,169 SIETIONLY DISTINGUISHED -- 5191 04:07:06,169 --> 04:07:07,003 PRECISELY DISTINGUISHED IN THE 5192 04:07:07,003 --> 04:07:09,305 BRAIN, BUT HOW IS THIS ACHIEVED? 5193 04:07:09,305 --> 04:07:10,974 SO HERE WE ARE ASKING THIS 5194 04:07:10,974 --> 04:07:13,243 QUESTION, YOU KNOW, HOW IS THE 5195 04:07:13,243 --> 04:07:15,211 VAGAL INTEROCEPTION SYSTEM 5196 04:07:15,211 --> 04:07:16,412 ORGANIZED TO PRESENT NUMEROUS 5197 04:07:16,412 --> 04:07:18,414 BODY SIGNALS TO THE BRAIN IN A 5198 04:07:18,414 --> 04:07:22,018 VERY PRECISE AND EFFICIENT WAY? 5199 04:07:22,018 --> 04:07:24,120 AND TO ADDRESS THAT QUESTION, WE 5200 04:07:24,120 --> 04:07:29,158 FIRST NEED TO THINK ABOUT WHAT 5201 04:07:29,158 --> 04:07:32,095 IS IMPORTANT FOR INTEROCEPTION 5202 04:07:32,095 --> 04:07:32,562 SNAM? 5203 04:07:32,562 --> 04:07:34,097 WHAT FEATURES DOES THE BRAIN 5204 04:07:34,097 --> 04:07:36,065 NEED TO KNOW TO RECOGNIZE WHAT 5205 04:07:36,065 --> 04:07:36,833 SIGNAL IT IS? 5206 04:07:36,833 --> 04:07:38,501 WE THINK THERE ARE AT LEAST 5207 04:07:38,501 --> 04:07:39,569 THREE INDEPENDENT KEY FEATURES 5208 04:07:39,569 --> 04:07:41,004 THE BRAIN NEEDS TO KNOW ABOUT 5209 04:07:41,004 --> 04:07:42,305 THE INTEROCEPTION SIGNAL. 5210 04:07:42,305 --> 04:07:43,973 THE FIRST ONE IS VISCERAL ORGAN 5211 04:07:43,973 --> 04:07:46,809 AND WE HAVE MANY VISCERAL 5212 04:07:46,809 --> 04:07:48,211 RESIDUAL ORGANS AND SIGNALS FROM 5213 04:07:48,211 --> 04:07:49,979 DIFFERENT ORGANS CLEARLY TELLING 5214 04:07:49,979 --> 04:07:51,180 THE BRAIN DIFFERENT THINGS GOING 5215 04:07:51,180 --> 04:07:52,048 ON IN THE BODY. 5216 04:07:52,048 --> 04:07:53,383 SECOND SOMEONE THE TISSUE LAYER. 5217 04:07:53,383 --> 04:07:55,051 EVEN WITHIN THE SAME VISCERAL 5218 04:07:55,051 --> 04:07:56,419 ORGAN THERE ARE MANY DIFFERENT 5219 04:07:56,419 --> 04:07:58,187 FISH EWE COMPOSITION AND IS 5220 04:07:58,187 --> 04:07:59,422 DIFFERENT LAYERS OF TISSUES AND 5221 04:07:59,422 --> 04:08:02,225 FROM THE SAME ORGAN, THE SIGNAL 5222 04:08:02,225 --> 04:08:03,860 FROM THE SAME ORGAN BUT 5223 04:08:03,860 --> 04:08:06,696 DIFFERENT TISSUE LAYERS IS ALSO 5224 04:08:06,696 --> 04:08:07,630 COMIENTING DIFFERENT 5225 04:08:07,630 --> 04:08:08,564 PHYSIOLOGICAL CHANGES TO THE 5226 04:08:08,564 --> 04:08:08,932 BRAIN. 5227 04:08:08,932 --> 04:08:12,969 THE THIRD ONE IS STIMULUS 5228 04:08:12,969 --> 04:08:14,270 MODALITY WHAT, THE SIGNAL IS, 5229 04:08:14,270 --> 04:08:15,471 WHETHER IT'S MECHANICAL CHANGES 5230 04:08:15,471 --> 04:08:17,373 OR THIS IS SOME CHEMICAL SIGNAL, 5231 04:08:17,373 --> 04:08:20,944 FOR EXAMPLE H THE ONES SIGNALS 5232 04:08:20,944 --> 04:08:25,848 RELEASED DURING FOOD INTAKE. 5233 04:08:25,848 --> 04:08:29,786 A FAITHFUL CODING OF ALL THESE 5234 04:08:29,786 --> 04:08:31,988 FEATURES IN THE VAGUE AT NEURONS 5235 04:08:31,988 --> 04:08:33,723 IS NECESSARY FOR ACCURATE SIGNAL 5236 04:08:33,723 --> 04:08:34,524 DISCRIMINATION IN THE BRAIN. 5237 04:08:34,524 --> 04:08:36,392 TO BETTER UNDERSTAND HOW ORGANS 5238 04:08:36,392 --> 04:08:38,361 ARE CODED WITHIN THESE SENSORY 5239 04:08:38,361 --> 04:08:40,463 NEURONS WE DEVELOPED A TOOL 5240 04:08:40,463 --> 04:08:43,166 CALLED PROJECTION SEQ BASED ON 5241 04:08:43,166 --> 04:08:44,701 SINGLE CELL RNA SEQUENCING SO 5242 04:08:44,701 --> 04:08:46,903 THE CONCEPT IS WE ARE 5243 04:08:46,903 --> 04:08:49,305 INTRODUCING MULTIPLEX BARCODES 5244 04:08:49,305 --> 04:08:50,606 INTO THESE VIRAL TRACERS SO WE 5245 04:08:50,606 --> 04:08:52,709 CAN LABEL THE NEURONS THAT 5246 04:08:52,709 --> 04:08:54,110 PROJECT TO DIFFERENT ORGANS 5247 04:08:54,110 --> 04:08:55,078 SIMULTANEOUSLY IN THE SAME 5248 04:08:55,078 --> 04:08:56,546 ANIMAL AND WE CAN STUDY THEIR 5249 04:08:56,546 --> 04:08:57,413 GENETIC SIGNATURES. 5250 04:08:57,413 --> 04:08:59,015 SO HERE IN DESCRIBING ONE 5251 04:08:59,015 --> 04:09:00,883 EXPERIMENT THAT WE INJECTED 5252 04:09:00,883 --> 04:09:03,086 SEVEN VISCERAL MAJOR ORGANS IN 5253 04:09:03,086 --> 04:09:04,420 THE ANIMAL SIMULTANEOUSLY EACH 5254 04:09:04,420 --> 04:09:06,289 ORGAN GETS A UNIQUE BARCODE AND 5255 04:09:06,289 --> 04:09:08,124 THEN WE CAN TAKE OUT THESE VAGAL 5256 04:09:08,124 --> 04:09:10,326 SENSORY NEURONS, WE DO SINGLE 5257 04:09:10,326 --> 04:09:12,428 CELL RNA SEQ AND KNOW WHAT GENE 5258 04:09:12,428 --> 04:09:14,430 IS EXPRESSED AND BASE #-D ON THE 5259 04:09:14,430 --> 04:09:15,598 BARCODES THEY EXPRESS WE KNOW 5260 04:09:15,598 --> 04:09:17,800 WHICH ORGANS THEY PROJECT TO. 5261 04:09:17,800 --> 04:09:19,168 ROOTITE I'M SHOWING YOU THIS MAP 5262 04:09:19,168 --> 04:09:23,506 OF THE VAGAL SENSORY NEURONS AND 5263 04:09:23,506 --> 04:09:25,475 EACH DOT REPRESENTS A NEURON AND 5264 04:09:25,475 --> 04:09:27,343 COLOR CODES FOLLOW THE ORGANS 5265 04:09:27,343 --> 04:09:28,077 THEY INNERVATE. 5266 04:09:28,077 --> 04:09:29,846 EVEN FROM THIS MAP YOU CAN 5267 04:09:29,846 --> 04:09:31,381 CLEARLY SEE THAT THE NEURONS 5268 04:09:31,381 --> 04:09:33,683 ENTER VAITING DIFFERENT NEURONS 5269 04:09:33,683 --> 04:09:37,553 ARE LARGELY GENETICALLY 5270 04:09:37,553 --> 04:09:39,856 DISAGGREGATED DISH SEGREGATE. 5271 04:09:39,856 --> 04:09:41,024 VISCERAL ORGAN TRAJECTORY SEEMS 5272 04:09:41,024 --> 04:09:46,295 TO CODE THE ORGANS ALONG THE 5273 04:09:46,295 --> 04:09:49,232 BODY REQUEST CAUSAL AXIS. 5274 04:09:49,232 --> 04:09:52,869 SO ONE SIDE IS EXPLUNGZ 5275 04:09:52,869 --> 04:09:55,271 ESOPHAGUS -- EXPLUNGZ ESOPHAGUS, 5276 04:09:55,271 --> 04:09:57,573 UPPER, AND ON THE OTHER SIDE, 5277 04:09:57,573 --> 04:09:59,008 LIKE INTESTINAL ORG EXPANS 5278 04:09:59,008 --> 04:09:59,208 COLON. 5279 04:09:59,208 --> 04:10:01,177 9 LOCATION OF THE ORGANS IS LONG 5280 04:10:01,177 --> 04:10:04,147 THE BODY STRUCTURE CAUDAL AXIS 5281 04:10:04,147 --> 04:10:04,914 MATCHES VERY WELL WITH THE 5282 04:10:04,914 --> 04:10:07,216 LOCATION OF THESE NEURONS ALONG 5283 04:10:07,216 --> 04:10:08,418 THIS ORGAN TRAJECTORY. 5284 04:10:08,418 --> 04:10:11,487 SO THIS SUGGESTS THAT 5285 04:10:11,487 --> 04:10:13,122 DIFFERENTIAL GENE MODULES IN THE 5286 04:10:13,122 --> 04:10:14,991 VAGUE VAGUS NERVE ARE ACTUALLY 5287 04:10:14,991 --> 04:10:16,092 CODING THE LOCATION OF THE 5288 04:10:16,092 --> 04:10:20,163 VISCERAL ORGANS ALONG THE BODY'S 5289 04:10:20,163 --> 04:10:22,565 RAUSTRAL-CAUDAL AXIS AND ALSO 5290 04:10:22,565 --> 04:10:24,333 FOLLOWING GRADIENTS TO THEIR 5291 04:10:24,333 --> 04:10:25,635 TARGET ORGANS. 5292 04:10:25,635 --> 04:10:26,369 INTERESTINGLY IN ADDITION TO 5293 04:10:26,369 --> 04:10:28,271 THIS VISCERAL ORGAN TRAJECTORY, 5294 04:10:28,271 --> 04:10:31,140 WE FURTHER IDENTIFIED A SECOND 5295 04:10:31,140 --> 04:10:32,475 TRAJECTORY HERE AND ALSO WONDER 5296 04:10:32,475 --> 04:10:35,311 IF THE SECOND TRAJECTORY MAY 5297 04:10:35,311 --> 04:10:36,279 ALSO CAUSE ESSENTIAL 5298 04:10:36,279 --> 04:10:36,579 INFORMATION. 5299 04:10:36,579 --> 04:10:38,381 FOR THAT PURPOSE WE FURTHER 5300 04:10:38,381 --> 04:10:39,682 ANALYZED THE GENES THAT 5301 04:10:39,682 --> 04:10:40,983 DIFFERENTIALLY EXPRESS IN THIS 5302 04:10:40,983 --> 04:10:44,821 SECOND TRAJECTORY AND USE TOOLS, 5303 04:10:44,821 --> 04:10:48,224 MORE SPECIFICALLY CORRESPONDING 5304 04:10:48,224 --> 04:10:50,827 CRE MOUSE MICE TO GAIN GENETIC 5305 04:10:50,827 --> 04:10:52,261 TARGETS OF THESE CELLS. 5306 04:10:52,261 --> 04:10:54,564 USING CRE MOUSE LINES WE 5307 04:10:54,564 --> 04:10:58,201 INJECTED VIRUS INTO TO LABEL 5308 04:10:58,201 --> 04:10:59,936 CELLS NOT ONLY THEIR CELL BODIES 5309 04:10:59,936 --> 04:11:01,370 BUT THEIR ENTIRE PROJECTIONS 5310 04:11:01,370 --> 04:11:03,773 WITHIN THE BODY. 5311 04:11:03,773 --> 04:11:05,408 THEN FOO THESE ANIMALS WE CAN 5312 04:11:05,408 --> 04:11:07,243 TAKE OUT THE PARTICULAR VISCERAL 5313 04:11:07,243 --> 04:11:08,044 ORGANS, FOR EXAMPLE HERE I'M 5314 04:11:08,044 --> 04:11:09,212 SHOWING YOU THIS IS A MOUSE 5315 04:11:09,212 --> 04:11:10,746 HEART AND WE CAN DO TISSUE 5316 04:11:10,746 --> 04:11:12,849 CLEARING AND SO THAT WE CAN 5317 04:11:12,849 --> 04:11:15,818 IMAGE THE ENTIRE FLUORESCE ENLT 5318 04:11:15,818 --> 04:11:17,353 LABEL NERVE FIBERS WITHIN THE 5319 04:11:17,353 --> 04:11:17,987 ENTIRE ORGAN. 5320 04:11:17,987 --> 04:11:19,155 ON THE RIGHT I'M SHOWING YOU 5321 04:11:19,155 --> 04:11:21,624 THIS IS A MOUSE SENSORY 5322 04:11:21,624 --> 04:11:23,593 INNERVATION OF THE ENTIRE HEART, 5323 04:11:23,593 --> 04:11:26,662 OF THE ENTIRE MOUSE HEART AND WE 5324 04:11:26,662 --> 04:11:29,065 CAN FURTHER ZOOM IN TO LOOK AT 5325 04:11:29,065 --> 04:11:31,601 MANY DIFFERENT DETAILS SUCH AS 5326 04:11:31,601 --> 04:11:35,738 THEIR TERMINAL STRUCTURES. 5327 04:11:35,738 --> 04:11:37,473 THOUGH STRIKINGLY, WHAT WE 5328 04:11:37,473 --> 04:11:39,142 IDENTIFIED IS THIS SECOND 5329 04:11:39,142 --> 04:11:40,343 TRAJECTORY ACTUALLY CODE THE 5330 04:11:40,343 --> 04:11:41,077 TISSUE LAYERS. 5331 04:11:41,077 --> 04:11:43,379 SO NEURONS ON ONE SIDE OF THIS 5332 04:11:43,379 --> 04:11:44,947 TRAJECTORY WILL INNERVATE THE 5333 04:11:44,947 --> 04:11:46,883 SURFACE OF THE ORGAN IN MANY 5334 04:11:46,883 --> 04:11:48,117 DIFFERENT ORGANS, AND THE 5335 04:11:48,117 --> 04:11:49,519 NEURONS ON THE OTHER SIDE OF 5336 04:11:49,519 --> 04:11:51,821 THIS TRAJECTORY WILL INNERVATE 5337 04:11:51,821 --> 04:11:53,356 THE INNERMOST OF THE ORGAN CLOSE 5338 04:11:53,356 --> 04:11:54,657 TO THE LUMEN. 5339 04:11:54,657 --> 04:11:57,493 SO THIS DATA AGAIN SUGGESTS THAT 5340 04:11:57,493 --> 04:11:59,829 THERE'S A DIFFERENT SET OF GENE 5341 04:11:59,829 --> 04:12:03,332 MODULES THAT CODE THE TISSUE 5342 04:12:03,332 --> 04:12:04,534 WITHIN THE VAGUS NERVE. 5343 04:12:04,534 --> 04:12:08,604 BECAUSE THIS VISCERAL ORGAN 5344 04:12:08,604 --> 04:12:11,107 TRAJECTORY AND TISSUE LAYER ARE 5345 04:12:11,107 --> 04:12:12,308 ORTHOAGO NO, SUGGESTING TWO 5346 04:12:12,308 --> 04:12:14,610 DIFFERENT FEATURES ARE CODING 5347 04:12:14,610 --> 04:12:16,279 TWO INDEPENDENT CODING 5348 04:12:16,279 --> 04:12:17,613 DIMENSIONS IN THE VAGUS NERVE, 5349 04:12:17,613 --> 04:12:21,083 SO TOGETHER, THEY CONSTITUTE A 5350 04:12:21,083 --> 04:12:21,984 TWO-DIMENSIONAL GENETIC 5351 04:12:21,984 --> 04:12:23,085 REPRESENTATION OF THE BODY'S 5352 04:12:23,085 --> 04:12:25,121 INTERNAL FACE, WHICH PRECISE AM 5353 04:12:25,121 --> 04:12:27,657 TELL THE NEURON WHERE THE 5354 04:12:27,657 --> 04:12:29,425 SIGNALS COMING FROM. 5355 04:12:29,425 --> 04:12:32,495 NEXT WE ASK, YOU KNOW, HOW IS 5356 04:12:32,495 --> 04:12:34,330 THE STIMULUS CODED WITHIN THESE 5357 04:12:34,330 --> 04:12:34,564 NEURONS? 5358 04:12:34,564 --> 04:12:36,532 HOW DOES THE NEURON KNOW WHICH 5359 04:12:36,532 --> 04:12:39,135 STIMULUS IS DETECTING? 5360 04:12:39,135 --> 04:12:41,103 TO PRECISELY DETERMINE THE JECTD 5361 04:12:41,103 --> 04:12:42,338 IDENTITIES OF THE NEURONS 5362 04:12:42,338 --> 04:12:43,873 RESPOND TO GO A PARTICULAR ORGAN 5363 04:12:43,873 --> 04:12:45,508 CHANGE, WE DEVELOPED ANOTHER 5364 04:12:45,508 --> 04:12:54,050 TOOL WE CALL V CATFISH, CUPLIED 5365 04:12:54,050 --> 04:12:57,119 IN VIVO CALCIUM IMAGING. 5366 04:12:57,119 --> 04:12:59,088 IDENTIFYING NEURONS THAT RESPOND 5367 04:12:59,088 --> 04:13:01,390 SPECIFICALLY TO DIFFERENT ORGAN 5368 04:13:01,390 --> 04:13:02,391 CHALLENGES, DIFFERENT CHANGES. 5369 04:13:02,391 --> 04:13:05,328 THEN YOU TAKE THE GANGLION AND 5370 04:13:05,328 --> 04:13:08,831 THEN CUT THEM INTO SECTIONS AND 5371 04:13:08,831 --> 04:13:11,267 DO SPATIAL TRANSCRIPTOMICS AND 5372 04:13:11,267 --> 04:13:12,668 USE MATHEMATICAL APPROACH TO 5373 04:13:12,668 --> 04:13:14,303 REGISTER TWO DIFFERENT DATASETS 5374 04:13:14,303 --> 04:13:15,871 SO WE CAN PRECISELY DETERMINE 5375 04:13:15,871 --> 04:13:17,740 THE GENETIC SIGNATURE OF THOSE 5376 04:13:17,740 --> 04:13:19,041 NEURONS THAT RESPOND TO 5377 04:13:19,041 --> 04:13:20,443 DIFFERENT ORGAN CHALLENGES. 5378 04:13:20,443 --> 04:13:22,345 FOR THE SAKE OF TIME, I WON'T BE 5379 04:13:22,345 --> 04:13:24,413 ABLE TO RUN INTO THE TECHNICAL 5380 04:13:24,413 --> 04:13:27,149 DETAILS HERE, SO WHAT WE 5381 04:13:27,149 --> 04:13:30,319 DISCOVER IS, SO FIRST THE SINGLE 5382 04:13:30,319 --> 04:13:32,521 CELL DEFINE VAGAL SENSORY NEURON 5383 04:13:32,521 --> 04:13:34,056 POPULATIONS HAVE VERY SIMILAR 5384 04:13:34,056 --> 04:13:35,458 RESPONSE PATTERNS ACROSS 5385 04:13:35,458 --> 04:13:39,528 DIFFERENT ORGANS, SUGGESTING 5386 04:13:39,528 --> 04:13:41,597 THAT THEIR RESPONSE PATTERNS 5387 04:13:41,597 --> 04:13:43,899 STIMULUS MODALITIES AND VISCERAL 5388 04:13:43,899 --> 04:13:45,468 ORGANS ARE INDEPENDENTLY CODED. 5389 04:13:45,468 --> 04:13:46,869 FOR EXAMPLE, ON THE LEFT I'M 5390 04:13:46,869 --> 04:13:48,938 SHOWING YOU THIS IS ONE NEURON 5391 04:13:48,938 --> 04:13:51,474 TYPE THAT RESPOND TO SNRECH A 5392 04:13:51,474 --> 04:13:52,908 VERY SUSTAINED KINETICS IN MANY 5393 04:13:52,908 --> 04:13:54,977 DIFFERENT ORGANS AND THERE ARE 5394 04:13:54,977 --> 04:13:56,412 ALSO GENETICALLY DEFINED NEURON 5395 04:13:56,412 --> 04:13:57,813 TYPES THAT WILL HAVE THIS 5396 04:13:57,813 --> 04:13:59,548 TRANSIENT RESPONSE TO STRETCH IN 5397 04:13:59,548 --> 04:14:00,449 DIFFERENT ORGANS. 5398 04:14:00,449 --> 04:14:01,884 ON THE OTHER HAND, WE ARE ALSO 5399 04:14:01,884 --> 04:14:06,689 VERY SURPRISED TO SEE THAT THE 5400 04:14:06,689 --> 04:14:07,890 NEURON RESPONSE PATTERNS ARE 5401 04:14:07,890 --> 04:14:09,525 LARGELY UNCOUPLED FROM THEIR 5402 04:14:09,525 --> 04:14:10,626 SENSORY ENDINGS, WHICH 5403 04:14:10,626 --> 04:14:13,229 REPRESENTS THEIR TISSUE LAYERING 5404 04:14:13,229 --> 04:14:14,697 INFORMATION, SUGGESTING THAT 5405 04:14:14,697 --> 04:14:17,533 RESPONSE PATTERNS OR THE 5406 04:14:17,533 --> 04:14:20,169 STIMULUS MODALITIES ALSO CODED 5407 04:14:20,169 --> 04:14:21,237 INDEPENDENTLY OF THE TISSUE 5408 04:14:21,237 --> 04:14:21,470 LAYERS. 5409 04:14:21,470 --> 04:14:22,905 FOR EXAMPLE, WE HAVE NOTICED 5410 04:14:22,905 --> 04:14:25,074 MANY CASES THAT THE NEURONS WITH 5411 04:14:25,074 --> 04:14:26,609 DIFFERENT GENETIC SIGNATURES 5412 04:14:26,609 --> 04:14:28,344 WILL INNERVATE THE SAME ORGAN, 5413 04:14:28,344 --> 04:14:30,112 FORM THE SAME TYPE OF TERMINAL 5414 04:14:30,112 --> 04:14:32,315 STRUCTURES BUT THEY DETECT VERY 5415 04:14:32,315 --> 04:14:33,983 DIFFERENT SIGNALS FROM THOSE 5416 04:14:33,983 --> 04:14:34,250 LOCATIONS. 5417 04:14:34,250 --> 04:14:35,284 ON THE OTHER HAND, THE NEURONS 5418 04:14:35,284 --> 04:14:38,020 WITH THE SAME GENETIC 5419 04:14:38,020 --> 04:14:40,423 SIGNATURES, THEY SHARE THE SAME 5420 04:14:40,423 --> 04:14:44,193 BASICALLY VERY SIMILAR RESPONSE 5421 04:14:44,193 --> 04:14:45,695 PATTERNS, FOR EXAMPLE, FOR ALL 5422 04:14:45,695 --> 04:14:48,364 THE DETECTING STRETCH, IN 5423 04:14:48,364 --> 04:14:49,298 DIFFERENT -- FROM DIFFERENT 5424 04:14:49,298 --> 04:14:51,167 ORGANS BUT THEY FORM VERY 5425 04:14:51,167 --> 04:14:52,935 DIFFERENT TERMINAL STRUCTURES 5426 04:14:52,935 --> 04:14:54,370 WITHIN DIFFERENT ORGANS. 5427 04:14:54,370 --> 04:14:58,407 SO PUTTING EVERYTHING TOGETHER, 5428 04:14:58,407 --> 04:15:01,344 OUR STUDY SHOW THAT THREE 5429 04:15:01,344 --> 04:15:04,080 INDEPENDENT FEATURES TOURS OF 5430 04:15:04,080 --> 04:15:04,947 INTEROCEPTION SIGNAL ARE CODED 5431 04:15:04,947 --> 04:15:06,716 IN THREE INDEPENDENT CODING 5432 04:15:06,716 --> 04:15:07,817 DIMENSIONS IN THE VAGUS NERVE 5433 04:15:07,817 --> 04:15:10,319 AND THIS MULTIDIMENSIONAL CODING 5434 04:15:10,319 --> 04:15:11,454 ARCHITECTURE ACTUALLY ENABLES 5435 04:15:11,454 --> 04:15:15,358 THE VAGUS NERVE TO GENERATE THIS 5436 04:15:15,358 --> 04:15:18,094 TO EXPAND VERY EFFECTIVELY FOR 5437 04:15:18,094 --> 04:15:21,497 ITS DIVERSITY AND GENERATES 5438 04:15:21,497 --> 04:15:22,798 NUMEROUS PARALLEL STREAMS TO 5439 04:15:22,798 --> 04:15:24,867 PRESENT THE SIGNALS FROM THE 5440 04:15:24,867 --> 04:15:26,168 PERIPHERAL ORG TOONS THE BRAIN. 5441 04:15:26,168 --> 04:15:28,704 AND THEY BELIEVE THIS IS A 5442 04:15:28,704 --> 04:15:31,006 PERFECT EXAMPLE OR DEMONSTRATION 5443 04:15:31,006 --> 04:15:34,176 OF THE EFFICIENT SENSORY CODING 5444 04:15:34,176 --> 04:15:36,312 THEORY IN THE INTEROCEPTION 5445 04:15:36,312 --> 04:15:38,214 SYSTEM, THE SENSORY NEURONS USE 5446 04:15:38,214 --> 04:15:39,415 THE MINIMUM RESOURCES TO CODE 5447 04:15:39,415 --> 04:15:42,385 THE MAXIMUM INFORMATION H HAD. 5448 04:15:42,385 --> 04:15:45,454 SO IN SUMMARY, TODAY I'M SHOWING 5449 04:15:45,454 --> 04:15:47,957 YOU OUR STUDY REVEALED A 5450 04:15:47,957 --> 04:15:48,958 MULTIDIMENSIONAL CODING 5451 04:15:48,958 --> 04:15:50,593 ARCHITECTURE OF THE VAGAL 5452 04:15:50,593 --> 04:15:51,994 INTEROCEPTION SYSTEM USING THIS 5453 04:15:51,994 --> 04:15:53,662 CODING STRATEGY THE VAGUS NERVE 5454 04:15:53,662 --> 04:15:55,264 IS ABLE TO GENERATE A LARGE 5455 04:15:55,264 --> 04:15:57,466 NUMBER OF PARALLEL STRINGS TO 5456 04:15:57,466 --> 04:15:59,101 PRESENT THE SIGNALS FROM THE 5457 04:15:59,101 --> 04:16:00,770 PERIPHERAL ORG TOONS THE TBLAIN 5458 04:16:00,770 --> 04:16:03,272 A VERY EFFICIENT -- TO THE BRAIN 5459 04:16:03,272 --> 04:16:04,907 IN A VERY EFFICIENT AND 5460 04:16:04,907 --> 04:16:05,708 EFFECTIVE MANNER. 5461 04:16:05,708 --> 04:16:06,876 I WANT TO THANK EVERYONE 5462 04:16:06,876 --> 04:16:08,411 INVOLVED IN THIS PROJECT, MOST 5463 04:16:08,411 --> 04:16:13,682 OF THE WORK WAS DONE ABOUT VERY 5464 04:16:13,682 --> 04:16:14,984 TALENTED POST-DOC CURRENTLY ON 5465 04:16:14,984 --> 04:16:21,123 THE JOG MARKET, QIANCHENG ZHAO, 5466 04:16:21,123 --> 04:16:24,093 AN AMAZING GRADUATE STUDENT WHO 5467 04:16:24,093 --> 04:16:25,494 PERFORMED ALL THE EXPERIMENTS 5468 04:16:25,494 --> 04:16:29,765 AND OUR LONG-TERM COLLABORATOR 5469 04:16:29,765 --> 04:16:33,702 LE ZHANG, DEVELOPED THIS SEQ 5470 04:16:33,702 --> 04:16:35,438 APPROACH AND DATA ANALYSIS AND 5471 04:16:35,438 --> 04:16:39,408 WE ALSO THANK ALL THE FUNDING 5472 04:16:39,408 --> 04:16:42,111 AGENCIES INCLUDING NCCIH FOR 5473 04:16:42,111 --> 04:16:43,846 FUNDING REALLY IMPORTANT FUNDING 5474 04:16:43,846 --> 04:16:46,949 FOR OUR WORK AS WELL AS NIR 5475 04:16:46,949 --> 04:16:49,151 DIRECTORS AND MANY OTHER 5476 04:16:49,151 --> 04:16:50,553 FOUNDATIONS AND THANK YOU FOR 5477 04:16:50,553 --> 04:16:58,994 YOUR ATTENTION. 5478 04:16:58,994 --> 04:16:59,829 >> OKAY. 5479 04:16:59,829 --> 04:17:03,098 WE HAVE TIME FOR A QUESTION. 5480 04:17:03,098 --> 04:17:08,437 >> SAME CONCEPT. 5481 04:17:08,437 --> 04:17:09,905 >> THIS WAS A GREAT TALK. 5482 04:17:09,905 --> 04:17:11,674 MY QUESTION WAS, DO YOU HAVE ANY 5483 04:17:11,674 --> 04:17:13,776 ONGOING EXPERIMENT LOOKING AFT A 5484 04:17:13,776 --> 04:17:18,047 CODING ARCHITECTURE ABOVE THE 5485 04:17:18,047 --> 04:17:21,317 NODUS GANGLION INTO A CORTICAL 5486 04:17:21,317 --> 04:17:23,853 OR BRAINSTEM OR OTHER CORTICAL 5487 04:17:23,853 --> 04:17:24,153 STRUCTURES? 5488 04:17:24,153 --> 04:17:25,688 GROO THAT IS A GREAT QUESTION. 5489 04:17:25,688 --> 04:17:26,789 CURRENTLY WE DON'T HAVE ANY 5490 04:17:26,789 --> 04:17:31,927 LOOKING AT ABOVE THAT, BUT MY 5491 04:17:31,927 --> 04:17:33,462 POST-DOC MENTOR STEVE -- LAB IS 5492 04:17:33,462 --> 04:17:36,632 LOOKING AT NTS CODING LOOKING AT 5493 04:17:36,632 --> 04:17:37,933 IMAGE SO THERE'S SOME REALLY 5494 04:17:37,933 --> 04:17:41,237 INTERESTING WORK THERE. 5495 04:17:41,237 --> 04:17:44,073 AND THE CODING SEEMS TO BE 5496 04:17:44,073 --> 04:17:46,175 SLIGHTLY DIFFERENT FROM THE 5497 04:17:46,175 --> 04:17:49,778 CODING LOGIC WITHIN THE -- BUT I 5498 04:17:49,778 --> 04:17:50,846 BELIEVE THERE'S A REASON FOR IT 5499 04:17:50,846 --> 04:17:53,249 BECAUSE WE DO HAVE A LARGE 5500 04:17:53,249 --> 04:17:55,684 NUMBER OF NEURONS THAT CAN SPEND 5501 04:17:55,684 --> 04:17:59,188 A LOT OF COMPUTATIONAL EFFORT 5502 04:17:59,188 --> 04:18:01,023 ONTO CODING THE INFORMATION 5503 04:18:01,023 --> 04:18:02,491 EXPINT GRATING THE INFORMATION. 5504 04:18:02,491 --> 04:18:03,959 WE ONLY HAVE VERY, VERY FEW 5505 04:18:03,959 --> 04:18:05,661 NUMBER OF SENSORY NEURONS IN 5506 04:18:05,661 --> 04:18:06,328 VAGUS NERVE. 5507 04:18:06,328 --> 04:18:08,497 SO FOR EXAMPLE, IN MOUSE WE ARE 5508 04:18:08,497 --> 04:18:10,799 TALKING ABOUT 5,000 NEURONS IN 5509 04:18:10,799 --> 04:18:15,404 TOTAL FROM BOTH THE NERVE, SO 5510 04:18:15,404 --> 04:18:18,908 THEY MUST USE VERY DIFFERENT 5511 04:18:18,908 --> 04:18:19,909 STRATEGIES -- VERY DIFFERENT 5512 04:18:19,909 --> 04:18:21,210 CODING STRATEGIES FOR 5513 04:18:21,210 --> 04:18:21,544 TRANSMITTING. 5514 04:18:21,544 --> 04:18:21,877 >> THANK YOU. 5515 04:18:21,877 --> 04:18:27,149 >> THANK YOU VERY MUCH, RUI. 5516 04:18:27,149 --> 04:18:28,884 SO OUR LAST SPEAKER BEFORE THE 5517 04:18:28,884 --> 04:18:34,456 GENERAL DISCUSSION IS RICHARD 5518 04:18:34,456 --> 04:18:39,328 LANG. 5519 04:18:39,328 --> 04:18:40,963 >> THANK YOU VERY MUCH TO THE 5520 04:18:40,963 --> 04:18:42,164 ORGANIZERS FOR INCORPORATING ME 5521 04:18:42,164 --> 04:18:42,932 INTO THIS MEETING. 5522 04:18:42,932 --> 04:18:43,899 I'M DELIGHTED TO BE HERE. 5523 04:18:43,899 --> 04:18:45,768 I THINK YOU MIGHT FIND THIS ONE 5524 04:18:45,768 --> 04:18:47,836 IS A LITTLE BIT DIFFERENT. 5525 04:18:47,836 --> 04:18:50,039 I WOULD LIKE TO START WITH THIS. 5526 04:18:50,039 --> 04:18:51,674 THIS IS JUST A LITTLE REMINDER 5527 04:18:51,674 --> 04:18:55,144 ABOUT WHERE WE LIVE. 5528 04:18:55,144 --> 04:18:59,315 THIS IS OBVIOUSLY THE BALL OF 5529 04:18:59,315 --> 04:19:00,349 ROCK SUSPENDED IN SPACE. 5530 04:19:00,349 --> 04:19:02,084 THIS BALL OF ROCK ROTATES, AND 5531 04:19:02,084 --> 04:19:03,819 BECAUSE WE HAVE A STAR CLOSE BY, 5532 04:19:03,819 --> 04:19:06,021 IT MEANS WE ARE WASHED WITH THIS 5533 04:19:06,021 --> 04:19:07,923 RHYTHMIC PATTERN OF EM RADIATION 5534 04:19:07,923 --> 04:19:09,925 EVERY DAY. 5535 04:19:09,925 --> 04:19:11,694 AND THAT'S BEEN A REALLY 5536 04:19:11,694 --> 04:19:12,995 INTERESTING OPPORTUNITY FOR 5537 04:19:12,995 --> 04:19:15,731 EVOLUTIONARY PROCESSES. 5538 04:19:15,731 --> 04:19:17,700 SO WE HAVE EVOLVED A WHOLE 5539 04:19:17,700 --> 04:19:19,668 SERIES OF PHOTON DETECTION 5540 04:19:19,668 --> 04:19:21,971 MECHANISMS THAT ARE ADAPTIVE. 5541 04:19:21,971 --> 04:19:23,505 AND YOU'RE USING ONE OF THEM 5542 04:19:23,505 --> 04:19:25,240 NOW, THE VISUAL SYSTEM, AND IT'S 5543 04:19:25,240 --> 04:19:28,243 THIS REMARKABLE SYSTEM THAT CAN 5544 04:19:28,243 --> 04:19:30,446 DECODE OBJECTS BASED ON PHOTONS 5545 04:19:30,446 --> 04:19:32,247 THAT BOUNCE OFF THOSE OBJECTS, 5546 04:19:32,247 --> 04:19:33,816 YOU CAN DETERMINE TEXTURE AND 5547 04:19:33,816 --> 04:19:34,817 SHAPE AND ALL OF THESE 5548 04:19:34,817 --> 04:19:38,320 PROPERTIES OF THAT LOGIC -- 5549 04:19:38,320 --> 04:19:40,356 PROPERTIES OF THAT OBJECT, BUT 5550 04:19:40,356 --> 04:19:42,925 THERE ARE ALSO OTHER LICE SEEN 5551 04:19:42,925 --> 04:19:46,295 PATHWAYS YOU'RE FAMILIAR -- 5552 04:19:46,295 --> 04:19:47,830 LEISOSENE PATHWAYS YOU'RE 5553 04:19:47,830 --> 04:19:50,466 FAMILIAR W THERE'S THE CIRCADIAN 5554 04:19:50,466 --> 04:19:51,667 CLOCK SYSTEM, RESPONSIBLE FOR AT 5555 04:19:51,667 --> 04:19:53,969 LEAST A LOT OF OUR RHYTHMIC 5556 04:19:53,969 --> 04:19:55,504 PHYSIOLOGY, ALL OF OUR 5557 04:19:55,504 --> 04:19:57,439 PHYSIOLOGY IS RHYTHMIC, THE 5558 04:19:57,439 --> 04:19:58,574 CIRCADIAN CLOCK DOES SOME OF 5559 04:19:58,574 --> 04:19:58,774 THAT. 5560 04:19:58,774 --> 04:20:01,610 THERE ARE OTHER MECHANISMS FOR 5561 04:20:01,610 --> 04:20:05,447 GENERATING RHYTHMICITY AND THIS 5562 04:20:05,447 --> 04:20:07,616 CLOCK CAN BE PHOTON ENTRAINED 5563 04:20:07,616 --> 04:20:09,718 THROUGH LIGHT DETECTION IN THE 5564 04:20:09,718 --> 04:20:09,918 EYES. 5565 04:20:09,918 --> 04:20:11,787 BUT MY LAB HAS BEEN PARTICULARLY 5566 04:20:11,787 --> 04:20:13,055 INTERESTED IN THIS QUESTION, AND 5567 04:20:13,055 --> 04:20:15,391 THAT IS WHETHER THERE ARE OTHER 5568 04:20:15,391 --> 04:20:16,825 LIGHT DECODING PATHWAYS THAT 5569 04:20:16,825 --> 04:20:18,460 MATTER FOR OUR PHYSIOLOGY, AND 5570 04:20:18,460 --> 04:20:21,730 IT TURNS OUT THAT THERE ARE. 5571 04:20:21,730 --> 04:20:23,365 SO FOR THOSE OF YOU WHO ARE 5572 04:20:23,365 --> 04:20:27,002 UNFAMILIAR WITH THE OPSINS, THE 5573 04:20:27,002 --> 04:20:30,506 STRUCTURE YOU SEE ROTATING THERE 5574 04:20:30,506 --> 04:20:35,444 IS PALCZEWSKI'S CRYSTAL 5575 04:20:35,444 --> 04:20:39,615 STRUCTURE OF IT RHODOPSIN, FIRST 5576 04:20:39,615 --> 04:20:40,249 STRUCTURE THAT WAS SOLVED AND 5577 04:20:40,249 --> 04:20:43,052 THIS IS THE STRUCTURAL MOTIF FOR 5578 04:20:43,052 --> 04:20:45,087 ALL THE OPSINS. 5579 04:20:45,087 --> 04:20:45,954 THE CHART ON THE RIGHT IS 5580 04:20:45,954 --> 04:20:47,823 SHOWING YOU THE PHOTON 5581 04:20:47,823 --> 04:20:49,224 SENSITIVITY OF ALL THE HUMAN 5582 04:20:49,224 --> 04:20:51,093 OPSINS AND WHAT'S CLEAR FROM 5583 04:20:51,093 --> 04:20:52,394 STUDIES FROM MANY DIFFERENT 5584 04:20:52,394 --> 04:20:53,696 GROUPS OVER MANY YEARS IS THAT 5585 04:20:53,696 --> 04:20:55,230 THEY HAVE THESE DID I STINGT 5586 04:20:55,230 --> 04:20:56,532 RANGES OF PHOTONS THEY ARE 5587 04:20:56,532 --> 04:20:58,634 SENSITIVE TO, THAT PROBABLY 5588 04:20:58,634 --> 04:20:59,835 MATTERS FOR SOME OF THE 5589 04:20:59,835 --> 04:21:00,836 PHYSIOLOGY BECAUSE FOR EXAMPLE 5590 04:21:00,836 --> 04:21:02,237 COLOR VISION, YOU ARE COMPARING 5591 04:21:02,237 --> 04:21:05,307 THE ACTIVATION OF YOUR THREE 5592 04:21:05,307 --> 04:21:07,176 CONE OPS TO PERCEIVE A 5593 04:21:07,176 --> 04:21:10,646 PARTICULAR COLOR. 5594 04:21:10,646 --> 04:21:13,182 AND TODAY I'LL BE PRIMARILY 5595 04:21:13,182 --> 04:21:15,250 FOCUSING ON THE THREE CIRCLED 5596 04:21:15,250 --> 04:21:23,258 NONVISUAL OPSIN THAT IS ON OPN3, 5597 04:21:23,258 --> 04:21:25,961 OPN4 AND OPN5, THESE ARE ALL 5598 04:21:25,961 --> 04:21:27,830 STIMULATED PRIMARILY BY SHORT 5599 04:21:27,830 --> 04:21:29,198 WAVELENGTH PHOTONS. 5600 04:21:29,198 --> 04:21:32,134 SO THESE HAVE BEEN AROUND FOR 5601 04:21:32,134 --> 04:21:33,235 ABOUT 600 MILLION YEARS, BUT OF 5602 04:21:33,235 --> 04:21:34,970 COURSE EXCEPT FOR ABOUT THE LAST 5603 04:21:34,970 --> 04:21:36,772 200 YEARS WHEN WE INVENTED 5604 04:21:36,772 --> 04:21:38,273 ARTIFICIAL LIGHT, THE PRIMARY 5605 04:21:38,273 --> 04:21:40,576 SOURCE OF PHOTON LIE GANS FOR 5606 04:21:40,576 --> 04:21:43,112 THOSE OPSINS WAS THE SUN. 5607 04:21:43,112 --> 04:21:45,114 IT TURNS OUT IT PROBABLY 5608 04:21:45,114 --> 04:21:45,647 MATTERS. 5609 04:21:45,647 --> 04:21:48,150 SO WE GOT STARTED IN 5610 04:21:48,150 --> 04:21:49,351 INVESTIGATING THESE PATHWAYS 5611 04:21:49,351 --> 04:21:50,886 WITH WORK WE DID ON THE VISUAL 5612 04:21:50,886 --> 04:21:52,221 SYSTEM, AND THEM IMAGINE JUST 5613 04:21:52,221 --> 04:21:55,824 SHOWS YOU IN GREEN ANTIBODY 5614 04:21:55,824 --> 04:22:00,195 LABELING OF MELANO OPSIN IN 5615 04:22:00,195 --> 04:22:06,435 GANGLIA CELLS AND IN RED FOR O5 5616 04:22:06,435 --> 04:22:08,937 GANGLION CELLS, WE INVET GATED 5617 04:22:08,937 --> 04:22:10,472 WHAT THESE LIGHT SENSING CELLS 5618 04:22:10,472 --> 04:22:11,340 DID DEVELOPMENTALLY AND THIS IS 5619 04:22:11,340 --> 04:22:12,908 THE SCHEMATIC THAT DESCRIBES THE 5620 04:22:12,908 --> 04:22:13,976 MECHANISM AND BASICALLY WE 5621 04:22:13,976 --> 04:22:16,145 SHOWED THAT BOTH OF THOSE 5622 04:22:16,145 --> 04:22:16,912 LIGHT-SENSING PATHWAYS WERE 5623 04:22:16,912 --> 04:22:18,380 INVOLVED IN REGULATING VASCULAR 5624 04:22:18,380 --> 04:22:20,315 DEVELOPMENT IN THE EYE BUT ALSO 5625 04:22:20,315 --> 04:22:21,784 OTHER DEVELOPMENTAL EVENTS, AND 5626 04:22:21,784 --> 04:22:24,319 THE MECHANISM THAT'S SHOWN HERE 5627 04:22:24,319 --> 04:22:26,555 IS NOT SO IMPORTANT FOR TODAY'S 5628 04:22:26,555 --> 04:22:27,456 DISCUSSION, BUT SOME OF THE 5629 04:22:27,456 --> 04:22:29,958 CONCLUSIONS ARE. 5630 04:22:29,958 --> 04:22:31,693 SO ONE CONCLUSION WAS THAT LIGHT 5631 04:22:31,693 --> 04:22:34,463 COULD BE A DEVELOPMENTAL TIMING 5632 04:22:34,463 --> 04:22:34,630 CUE. 5633 04:22:34,630 --> 04:22:36,098 THAT WAS A LITTLE BIT UNUSUAL. 5634 04:22:36,098 --> 04:22:38,300 THE SECOND CONCLUSION WAS THAT 5635 04:22:38,300 --> 04:22:39,835 MAMMALIAN DEEP TISSUE LIGHT 5636 04:22:39,835 --> 04:22:41,036 SENSING WAS POSSIBLE, AND THE 5637 04:22:41,036 --> 04:22:42,237 REASON WE LEARNED THAT FROM 5638 04:22:42,237 --> 04:22:44,406 THESE STUDIES WAS THAT THE FIRST 5639 04:22:44,406 --> 04:22:47,576 PHASE OF BLUE LIGHT STIMULATION 5640 04:22:47,576 --> 04:22:49,011 MELAN OPSIN ACTUALLY OCCURRED IN 5641 04:22:49,011 --> 04:22:50,646 THE FETAL MOUSE EYE PRIOR TO 5642 04:22:50,646 --> 04:22:51,847 BIRTH SO IT WAS AN INDICATION 5643 04:22:51,847 --> 04:22:54,383 THAT PHOTONS COULD PENETRATE 5644 04:22:54,383 --> 04:22:55,918 SUFFICIENTLY TO STIMULATE THAT 5645 04:22:55,918 --> 04:22:58,520 OPSIN IN THE FETAL MOUSE EYE. 5646 04:22:58,520 --> 04:23:00,823 THIS REINFORCES THE IDEA THAT 5647 04:23:00,823 --> 04:23:02,024 OPSINS OFTEN WORK IN COMBINATION 5648 04:23:02,024 --> 04:23:03,759 IN PAIRS AND TRIPLETS TO GIVE 5649 04:23:03,759 --> 04:23:06,395 YOU INFORMATION DECODING. 5650 04:23:06,395 --> 04:23:09,364 NOW, WHEN WE WERE ASSESSING THE 5651 04:23:09,364 --> 04:23:10,465 EXPRESSION DOMAINS OF THESE 5652 04:23:10,465 --> 04:23:12,868 THREE OPSINS WE CAME ACROSS SOME 5653 04:23:12,868 --> 04:23:15,137 FAIRLY PROVOCATIVE LOCATIONS. 5654 04:23:15,137 --> 04:23:17,339 WHAT YOU'RE SEEING THERE IN THAT 5655 04:23:17,339 --> 04:23:21,376 IMAGE IS THE LINEAGE MARK FOR 5656 04:23:21,376 --> 04:23:23,445 OPSIN 5 IN THE PREOP PARTICULAR 5657 04:23:23,445 --> 04:23:25,214 AREA OF THE HYPOTHALAMUS, 5658 04:23:25,214 --> 04:23:26,748 RAISING THE POSSIBILITY THAT 5659 04:23:26,748 --> 04:23:29,151 MAMMALS HAD A DEEP BRAIN 5660 04:23:29,151 --> 04:23:29,484 PHOTORECEPTOR. 5661 04:23:29,484 --> 04:23:30,919 WE KNOW THAT THE BRAIN IS 5662 04:23:30,919 --> 04:23:34,590 IMPORTANT NUCLEUS FOR CONTROL OF 5663 04:23:34,590 --> 04:23:35,290 ENERGY METABOLISM, CLEARLY SOME 5664 04:23:35,290 --> 04:23:36,692 OF THE BIOLOGY WE'LL BE LOOKING 5665 04:23:36,692 --> 04:23:38,660 AT AND IN PARTICULAR IT CAN 5666 04:23:38,660 --> 04:23:40,195 REGULATE THERMOGENESIS AS WELL 5667 04:23:40,195 --> 04:23:42,931 AS OTHER ASPECTS OF ENERGY 5668 04:23:42,931 --> 04:23:43,265 HOMOEOSTASIS. 5669 04:23:43,265 --> 04:23:45,868 THE OTHER FAIRLY PROVOCATIVE 5670 04:23:45,868 --> 04:23:47,336 LOCATION FOR OPSIN EXPRESSION 5671 04:23:47,336 --> 04:23:54,109 WAS OPSIN 3 IN THE DIPLOSIGHTS 5672 04:23:54,109 --> 04:23:56,178 -- DIPLOSITES, 5673 04:23:56,178 --> 04:23:57,613 ENERGY STORAGE CELL, WHITE 5674 04:23:57,613 --> 04:23:59,248 ADIPOSE TISSUE HAS ENDOCRINE 5675 04:23:59,248 --> 04:24:00,349 FUNCTION AND WE OF COURSE FACE 5676 04:24:00,349 --> 04:24:02,017 THIS QUESTION ARE THOSE 5677 04:24:02,017 --> 04:24:03,986 EXTRAOCULAR TISSUES 5678 04:24:03,986 --> 04:24:04,319 LIGHT-SENSING? 5679 04:24:04,319 --> 04:24:05,520 AND THE ANSWER TO THAT QUESTION 5680 04:24:05,520 --> 04:24:07,256 IS A FIRM -- IS AFFIRMATIVE. 5681 04:24:07,256 --> 04:24:09,658 IN THE NEXT FEW SLIDES I'LL 5682 04:24:09,658 --> 04:24:13,729 SUMMARIZE FOR YOU WHAT WE FOUND. 5683 04:24:13,729 --> 04:24:15,898 SO IN THIS PAPER, WE SHOWED THAT 5684 04:24:15,898 --> 04:24:18,300 MAMMALS HAVE A DEEP BRAIN PHOTO 5685 04:24:18,300 --> 04:24:20,269 SENSOR, OPN5 IS SENSITIVE TO 5686 04:24:20,269 --> 04:24:21,036 VIOLET LIGHT. 5687 04:24:21,036 --> 04:24:22,571 WE REALIZED THAT SOME OF OUR 5688 04:24:22,571 --> 04:24:23,672 COLLEAGUES MIGHT BE FAIRLY 5689 04:24:23,672 --> 04:24:25,540 SKEPTICAL ABOUT THAT PROPOSAL, 5690 04:24:25,540 --> 04:24:27,476 SO WE BORROWED SOME MEASUREMENT 5691 04:24:27,476 --> 04:24:29,378 METHODS FROM THE PHYSICS WORLD 5692 04:24:29,378 --> 04:24:32,080 TO ACTUALLY SHOW THAT THE PHOTON 5693 04:24:32,080 --> 04:24:33,849 FLUX AT THAT LOCATION IN THE 5694 04:24:33,849 --> 04:24:35,050 PREOP PARTICULAR AREA WAS 5695 04:24:35,050 --> 04:24:38,220 SUFFICIENT TO ELICIT OPSIN 5696 04:24:38,220 --> 04:24:38,487 RESPONSES. 5697 04:24:38,487 --> 04:24:39,955 WE COULD ALSO SHOW, FOR EXAMPLE, 5698 04:24:39,955 --> 04:24:42,624 THAT IF YOU TOOK SLICE CULTURES 5699 04:24:42,624 --> 04:24:43,892 FROM THE PREOP PARTICULAR AREA 5700 04:24:43,892 --> 04:24:46,194 YOU COULD GOT A VERY NICE LIE 5701 04:24:46,194 --> 04:24:49,932 LET LIGHT-DEPENDENT RESPONSE -- 5702 04:24:49,932 --> 04:24:52,334 VERY NICE LIGHT-DEPENDENT, 5703 04:24:52,334 --> 04:24:54,636 VIOLET LIGHT-DEPENDENT RESPONSE, 5704 04:24:54,636 --> 04:24:55,938 THE GREEN LINE ON THE CHART. 5705 04:24:55,938 --> 04:24:58,006 BLUE LINE IS -- ANIMALS YOU 5706 04:24:58,006 --> 04:25:00,208 DON'T SEE A RESPONSE, AND THEN 5707 04:25:00,208 --> 04:25:00,809 POSITIVE CONTROL. 5708 04:25:00,809 --> 04:25:02,044 THAT WAS A PRETTY GOOD 5709 04:25:02,044 --> 04:25:03,278 INDICATION THAT THESE NEURONS 5710 04:25:03,278 --> 04:25:05,013 WERE DIRECTLY LIGHT-SENSING. 5711 04:25:05,013 --> 04:25:06,982 I ALREADY MENTIONED THAT PROCEED 5712 04:25:06,982 --> 04:25:11,586 OPTIC AREA NEURONS REGULATE 5713 04:25:11,586 --> 04:25:13,789 THERMOGENESIS SO IT WASN'T A BIG 5714 04:25:13,789 --> 04:25:15,657 SURPRISE WHEN WE LEARNED WITH 5715 04:25:15,657 --> 04:25:17,726 TEMPERATURE TELEMETRY SEN TORS 5716 04:25:17,726 --> 04:25:23,098 THAT THE -- SENSORS THAT THE O5 5717 04:25:23,098 --> 04:25:24,700 HAVE -- OPN5 HAVE HIGH 5718 04:25:24,700 --> 04:25:25,701 TEMPERATURE, BLUE LIGHT, YOU CAN 5719 04:25:25,701 --> 04:25:27,869 SEE IT GOES THROUGH THE 5720 04:25:27,869 --> 04:25:29,237 CIRCADIAN PATTERN, IT'S JUST 5721 04:25:29,237 --> 04:25:31,073 MUCH HIGHER THAN IT SHOULD BE 5722 04:25:31,073 --> 04:25:32,274 EXT DELTA BETWEEN THE CONTROL 5723 04:25:32,274 --> 04:25:36,445 THE GRAY TRACE AND OPN5 IS MUCH 5724 04:25:36,445 --> 04:25:37,512 LARGER DURING THE DAY, DO YOU 5725 04:25:37,512 --> 04:25:39,848 RECOLLECT THE LIGHT PHASE. 5726 04:25:39,848 --> 04:25:41,383 SO WE WERE ABLE TO SHOW USING 5727 04:25:41,383 --> 04:25:43,452 WHOLE ANIMALS THAT VIOLET LIGHT 5728 04:25:43,452 --> 04:25:45,420 STIMULATION COULD ELICIT ACUTE 5729 04:25:45,420 --> 04:25:47,289 CHANGES IN BODY TEMPERATURE AND 5730 04:25:47,289 --> 04:25:48,156 SO OF COURSE WE'RE THINKING 5731 04:25:48,156 --> 04:25:50,792 ABOUT THE PONLT THAT THIS 5732 04:25:50,792 --> 04:25:51,560 LIGHT-SENSING PATHWAY IS 5733 04:25:51,560 --> 04:25:53,295 PROVIDING TIME OF DAY 5734 04:25:53,295 --> 04:25:55,731 INFORMATION FOR MODULATING THE 5735 04:25:55,731 --> 04:25:57,466 NORMAL BODY TEMPERATURE CYCLE 5736 04:25:57,466 --> 04:26:00,535 YOU FIND IN A MAMMAL. 5737 04:26:00,535 --> 04:26:02,504 SO AS YOU WILL ALREADY HAVE 5738 04:26:02,504 --> 04:26:05,707 GUESSED, THE WAY THIS WORKS IS 5739 04:26:05,707 --> 04:26:08,210 THAT THIS OPN5 PREOP PARTICULAR 5740 04:26:08,210 --> 04:26:16,752 AREA HAS A SIM -- PRE-OPTIC AREB 5741 04:26:16,752 --> 04:26:20,889 ACTIVATION BY VIOLET NEURONS IS 5742 04:26:20,889 --> 04:26:23,091 TO SUPPRESS BROWN ADIPOSE TISSUE 5743 04:26:23,091 --> 04:26:24,526 MAKING SENSE BECAUSE NOCTURNAL 5744 04:26:24,526 --> 04:26:27,796 ANIMAL LIKE A MOUSE HAS LOW BODY 5745 04:26:27,796 --> 04:26:29,631 TEMPERATURE DURING LIGHT PHASE, 5746 04:26:29,631 --> 04:26:31,533 ITS INACTIVE STAGE. 5747 04:26:31,533 --> 04:26:34,936 BLUE LIGHT STIMULATION, WHITE 5748 04:26:34,936 --> 04:26:37,773 ADIPOSE POSE TISSUE, THE BLUE 5749 04:26:37,773 --> 04:26:44,246 LIGHT STIMULATION ENHANCES IN 5750 04:26:44,246 --> 04:26:48,750 LIE POLLICIS -- LYPOLISIS 5751 04:26:48,750 --> 04:26:50,052 RESPONSE, FATTY ACIDS, OUR 5752 04:26:50,052 --> 04:26:51,353 ENERGY THROUGHOUT THE BODY, BUT 5753 04:26:51,353 --> 04:26:56,725 IN PARTICULAR FOR BROWN ADIPOSE 5754 04:26:56,725 --> 04:26:58,026 CYTES, ANOTHER CIRCUMSTANCE 5755 04:26:58,026 --> 04:27:03,065 WHERE YOU HAVE TWO OPN5 AND OPN3 5756 04:27:03,065 --> 04:27:05,600 REGULATING BODY TEMPERATURE 5757 04:27:05,600 --> 04:27:06,268 HOMOEOSTASIS. 5758 04:27:06,268 --> 04:27:07,569 GIVEN THESE FINDINGS WE THINK 5759 04:27:07,569 --> 04:27:09,337 THESE PATHWAYS ARE FUNDAMENTALLY 5760 04:27:09,337 --> 04:27:10,739 ABOUT GIVING YOU ENERGY 5761 04:27:10,739 --> 04:27:11,940 HOMOEOSTASIS AND PROVIDING TIME 5762 04:27:11,940 --> 04:27:14,342 OF DAY INFORMATION TO CREATE THE 5763 04:27:14,342 --> 04:27:16,511 RIGHT ENERGY STATE FOR A GIVEN 5764 04:27:16,511 --> 04:27:18,947 PART OF THE DAY. 5765 04:27:18,947 --> 04:27:20,348 AND WE ARE VERY CURIOUS ABOUT 5766 04:27:20,348 --> 04:27:22,551 THE POSSIBILITY OF SENSORY 5767 04:27:22,551 --> 04:27:23,518 FEEDBACK, OF COURSE, THERE WILL 5768 04:27:23,518 --> 04:27:25,754 BE SOME BEAUTIFUL WORK ON THAT 5769 04:27:25,754 --> 04:27:26,922 RECENT -- THERE'S BEEN SOME 5770 04:27:26,922 --> 04:27:28,457 BEAUTIFUL WORK ON THAT RECENTLY. 5771 04:27:28,457 --> 04:27:29,858 WHAT WE'RE SUGGESTING HERE IS 5772 04:27:29,858 --> 04:27:32,294 THAT WE HAVE IDENTIFIED A NEW 5773 04:27:32,294 --> 04:27:33,795 MECHANISM FOR THE MECHANISM OF 5774 04:27:33,795 --> 04:27:35,464 ENERGY METABOLISM IN WHICH THERE 5775 04:27:35,464 --> 04:27:37,532 IS INTIMATE CUP THROING THE 5776 04:27:37,532 --> 04:27:39,968 SUNLIGHT CYCLE -- COUPLING TO 5777 04:27:39,968 --> 04:27:41,269 THE SUNLIGHT CYCLE. 5778 04:27:41,269 --> 04:27:42,571 WE'RE PARTICULARLY INTERESTED IN 5779 04:27:42,571 --> 04:27:43,872 SENSORY FEEDBACK PARTLY BECAUSE 5780 04:27:43,872 --> 04:27:44,539 OF THESE DATA. 5781 04:27:44,539 --> 04:27:46,608 SO WHAT YOU'RE SEEING IN THE 5782 04:27:46,608 --> 04:27:48,143 ROTATING IMAGE ON THE LEFT IS A 5783 04:27:48,143 --> 04:27:50,112 DORSAL ROOT GANGLION IN WHICH 5784 04:27:50,112 --> 04:27:57,018 WE'VE IMAGED REPORTERS FOR OPN3 5785 04:27:57,018 --> 04:27:59,654 EGF AND LYNN LINEAGE MARK 5786 04:27:59,654 --> 04:28:03,892 FOR OPN5, AI14 THIS. 5787 04:28:03,892 --> 04:28:06,328 A FEATURE OF ALL LEVELS OF DRG, 5788 04:28:06,328 --> 04:28:09,698 WORK DONE BY JONATHAN RAIS THE 5789 04:28:09,698 --> 04:28:11,366 GENTLEMAN IN THE HAT, AND YOU'RE 5790 04:28:11,366 --> 04:28:13,768 ALSO SEE ON THE RIGHT-HAND SIDE 5791 04:28:13,768 --> 04:28:17,572 HERE THE TRIGEMINAL GANGLION 5792 04:28:17,572 --> 04:28:19,341 SIMILARLY EXPRESSES BOTH, 5793 04:28:19,341 --> 04:28:21,776 RAISING THE POSSIBILITY THAT 5794 04:28:21,776 --> 04:28:24,513 THESE NURS ONS ARE -- NEURONS 5795 04:28:24,513 --> 04:28:25,580 ARE LIGHT SENSING. 5796 04:28:25,580 --> 04:28:26,715 THERE'S EVIDENCE OUT THERE TO 5797 04:28:26,715 --> 04:28:29,551 SUGGEST THAT THE TRIGEMINAL 5798 04:28:29,551 --> 04:28:31,319 GANGLION IS LIGHT SENSING 5799 04:28:31,319 --> 04:28:32,854 EX-VIVO AND WE'VE ALSO GENERATED 5800 04:28:32,854 --> 04:28:34,389 QUITE A BIT OF DATA LATELY TO 5801 04:28:34,389 --> 04:28:37,425 SUGGEST THIS IS THE CASE. 5802 04:28:37,425 --> 04:28:41,062 SO THAT GIVES US ANOTHER WHOLE 5803 04:28:41,062 --> 04:28:42,030 LEVEL OF POSSIBILITY WHEN WE 5804 04:28:42,030 --> 04:28:43,465 THINK ABOUT OUR GRAND SCHEME FOR 5805 04:28:43,465 --> 04:28:46,401 HOW LIGHT-SENSING PATHWAYS MIGHT 5806 04:28:46,401 --> 04:28:48,170 REGULATE ENERGY HOMOEOSTASIS. 5807 04:28:48,170 --> 04:28:51,439 SO OBVIOUSLY WHAT WE'RE SUING -- 5808 04:28:51,439 --> 04:28:52,641 SO OBVIOUSLY WHAT WE'RE 5809 04:28:52,641 --> 04:28:55,243 SUGGESTING HERE IS THAT THE ROOT 5810 04:28:55,243 --> 04:28:56,311 GANGLIA MIGHT PROVIDE FEEDBACK 5811 04:28:56,311 --> 04:28:58,113 TIME OF DAY INFORMATION THAT 5812 04:28:58,113 --> 04:29:01,850 REGULATES INPUT CENTRALLY AND 5813 04:29:01,850 --> 04:29:03,718 WE'LL PROBABLY BE TALKING ABOUT 5814 04:29:03,718 --> 04:29:04,920 LIGHT-DEPENDENT MODULATION OF 5815 04:29:04,920 --> 04:29:07,088 EXISTING INPUT. 5816 04:29:07,088 --> 04:29:12,327 THE DRG'S THAT EXPRESS OPN5 AND 5817 04:29:12,327 --> 04:29:16,665 OPN3 FALL INTO MECHANOSENSES, 5818 04:29:16,665 --> 04:29:17,432 SOME OF THE RESPONSES WE'LL BE 5819 04:29:17,432 --> 04:29:18,200 LOOKING AT. 5820 04:29:18,200 --> 04:29:19,668 I WOULD ADD WE'RE ESPECIALLY 5821 04:29:19,668 --> 04:29:21,836 INTERESTED IN HOW THE LUNG MIGHT 5822 04:29:21,836 --> 04:29:24,172 BE INVOLVED IN THIS PATHWAY 5823 04:29:24,172 --> 04:29:27,475 BECAUSE IN THIS CIRCUIT, BECAUSE 5824 04:29:27,475 --> 04:29:28,643 OBVIOUSLY IT'S THE ORGAN THAT 5825 04:29:28,643 --> 04:29:30,412 TAKES UP THE OXYGEN THAT IS A 5826 04:29:30,412 --> 04:29:32,714 CRUCIAL COMPONENT OF ENERGY 5827 04:29:32,714 --> 04:29:33,048 HOMOEOSTASIS. 5828 04:29:33,048 --> 04:29:35,750 WE'RE CURRENTLY WORKING WITH -- 5829 04:29:35,750 --> 04:29:38,186 ON PROSECUTING SOME OF THIS 5830 04:29:38,186 --> 04:29:40,455 ANALYSIS AND WE ACTUALLY FOUND 5831 04:29:40,455 --> 04:29:43,558 THAT OPN3 IS EXPRESSED IN SOME 5832 04:29:43,558 --> 04:29:45,627 OF THE NEURONS OF THE VAGAL 5833 04:29:45,627 --> 04:29:45,860 GANGLIA. 5834 04:29:45,860 --> 04:29:47,195 THAT IS THE GRAND SCHEME WITH 5835 04:29:47,195 --> 04:29:48,630 LOTS OF QUESTIONS REMAINING, BUT 5836 04:29:48,630 --> 04:29:50,165 I THOUGHT I WOULD FINISH BY JUST 5837 04:29:50,165 --> 04:29:50,999 SHOWING YOU THIS. 5838 04:29:50,999 --> 04:29:52,934 THIS IS A SCHEMATIC THAT SHOWS 5839 04:29:52,934 --> 04:29:54,669 YOU ALL THE MOUSE BODY PARTS 5840 04:29:54,669 --> 04:29:56,871 THAT WE NOW KNOW ARE LIGHT 5841 04:29:56,871 --> 04:29:58,673 SENSING, AND OF COURSE OBVIOUSLY 5842 04:29:58,673 --> 04:30:00,475 WE HAVE RETINA AND CORNEA, I 5843 04:30:00,475 --> 04:30:03,211 COULD ALSO TELL YOU THAT THE 5844 04:30:03,211 --> 04:30:05,080 OCULAR LENS, THAT STRANGE 5845 04:30:05,080 --> 04:30:05,914 TRANSPARENT OBJECT THAT YOU HAVE 5846 04:30:05,914 --> 04:30:08,116 IN THE MIDDLE OF YOUR EYE IS 5847 04:30:08,116 --> 04:30:11,953 ALSO INDEPENDENTLY LIGHT SENSING 5848 04:30:11,953 --> 04:30:15,991 I TOLD YOU ABOUT PRE-OPTIC 5849 04:30:15,991 --> 04:30:17,759 NEURONS DIRECTLY LIGHT SENSING. 5850 04:30:17,759 --> 04:30:21,162 I HAVEN'T MENTIONED MELANOCYTE 5851 04:30:21,162 --> 04:30:24,099 PRECURSORS, SO WORK FROM MY 5852 04:30:24,099 --> 04:30:26,401 COLLABORATORS HAVE SHOWN 5853 04:30:26,401 --> 04:30:27,702 MELANOCYTE PRECURSORS IN THE 5854 04:30:27,702 --> 04:30:29,070 SKIN ASSOCIATED WITH HAIR 5855 04:30:29,070 --> 04:30:30,472 FOLLICLES THAT EXPRESS OPN5 AND 5856 04:30:30,472 --> 04:30:31,873 ARE LIGHT SENSE AND GO THEY 5857 04:30:31,873 --> 04:30:34,843 ACTUALLY FUNCTION AS A PACEMAKER 5858 04:30:34,843 --> 04:30:36,578 CELL FOR CIRCADIAN CLOCK IN THE 5859 04:30:36,578 --> 04:30:38,580 SKIN THAT FUNCTIONS QUITE 5860 04:30:38,580 --> 04:30:40,415 INDEPENDENTLY OF THE OTHER 5861 04:30:40,415 --> 04:30:42,617 CIRCADIAN RHYTHMS. 5862 04:30:42,617 --> 04:30:51,359 SO THEN WHITED ADIPOCYTES AND 5863 04:30:51,359 --> 04:30:53,361 TRIGEMINAL GANGLION, DORSAL ROOT 5864 04:30:53,361 --> 04:30:54,462 GANGLIA, OTHER EXAMPLES OF LIGHT 5865 04:30:54,462 --> 04:30:55,964 SENSING TISSUES COMING, THE 5866 04:30:55,964 --> 04:30:58,500 IMPRESSION YOU GET IS THAT THE 5867 04:30:58,500 --> 04:30:59,701 MAMMALIAN SYSTEM IS ENTIRELY SET 5868 04:30:59,701 --> 04:31:01,436 UP TO DECODE LIGHT INFORMATION 5869 04:31:01,436 --> 04:31:03,104 ON REGULATE OUR PHYSIOLOGY AND 5870 04:31:03,104 --> 04:31:04,272 SINCE WE CHOOSE TO LIVE THE WAY 5871 04:31:04,272 --> 04:31:06,675 WE DO, INSIDE, NOT IN SUNSHINE, 5872 04:31:06,675 --> 04:31:07,809 WE HAVE A FEW LITTLE PROBLEMS 5873 04:31:07,809 --> 04:31:09,411 AND WE CAN TALK ABOUT WHAT THE 5874 04:31:09,411 --> 04:31:12,480 DISEASE IMPLICATIONS MIGHT BE. 5875 04:31:12,480 --> 04:31:13,915 BUT HERE IS THE GRAND 5876 04:31:13,915 --> 04:31:15,884 CONCLUSION, A REMINDER THAT 5877 04:31:15,884 --> 04:31:17,285 THERE IS INTIMATE LINKAGE 5878 04:31:17,285 --> 04:31:20,455 BETWEEN MAMMALIAN PHYSIOLOGY AND 5879 04:31:20,455 --> 04:31:24,526 THE PHOTON LIGANDS FOR THE OPSIN 5880 04:31:24,526 --> 04:31:26,294 PROTON RECEPTORS PRODUCED BY THE 5881 04:31:26,294 --> 04:31:26,594 SUN. 5882 04:31:26,594 --> 04:31:27,796 LASTLY TO ACKNOWLEDGE ALL THE 5883 04:31:27,796 --> 04:31:29,130 PEOPLE THAT DO THE WORK, THIS IS 5884 04:31:29,130 --> 04:31:30,532 MY CURRENT LAB CREW IN THE 5885 04:31:30,532 --> 04:31:32,767 PICTURE, FORMER AND PRESENT LAB 5886 04:31:32,767 --> 04:31:34,402 MEMBERS, ALL OF WHOM MADE A 5887 04:31:34,402 --> 04:31:35,603 WONDERFUL CONTRIBUTION TO THIS 5888 04:31:35,603 --> 04:31:35,804 WORK. 5889 04:31:35,804 --> 04:31:37,472 I'VE HAD SOME EXCEPTIONAL 5890 04:31:37,472 --> 04:31:38,440 COLLABORATORS AND I PARTICULARLY 5891 04:31:38,440 --> 04:31:43,345 WANT TO IDENTIFY RAN DID I 5892 04:31:43,345 --> 04:31:47,415 SEALEY TUCKER, AND -- VENTURING 5893 04:31:47,415 --> 04:31:48,883 INTO THE WORLD OF METABOLISM. 5894 04:31:48,883 --> 04:31:50,752 WITH THAT, THANK YOU VERY MUCH 5895 04:31:50,752 --> 04:31:58,259 FOR YOUR ATTENTION. 5896 04:31:58,259 --> 04:31:59,394 >> THANK YOU VERY MUCH. 5897 04:31:59,394 --> 04:32:03,164 WE HAVE TIME FOR A QUESTION. 5898 04:32:03,164 --> 04:32:05,433 >> I'M FROM THE UNIVERSITY OF 5899 04:32:05,433 --> 04:32:05,667 ARIZONA. 5900 04:32:05,667 --> 04:32:07,602 THIS IS ABSOLUTELY FASCINATING. 5901 04:32:07,602 --> 04:32:08,236 FANTASTIC WORK. 5902 04:32:08,236 --> 04:32:10,138 I WOULD LIKE TO KNOW WHETHER YOU 5903 04:32:10,138 --> 04:32:16,211 HAVE ANYTHING ON THE GREEN LIGHT 5904 04:32:16,211 --> 04:32:17,545 BECAUSE -- FROM THE UNIVERSITY 5905 04:32:17,545 --> 04:32:21,583 OF ARIZONA SHOWED GREEN LIGHT IS 5906 04:32:21,583 --> 04:32:23,351 ANTI-ENERGETIC, ESPECIALLY WITH 5907 04:32:23,351 --> 04:32:25,520 BRAIN DISORDERS THAT INVOLVE 5908 04:32:25,520 --> 04:32:25,854 INTEROCEPTION. 5909 04:32:25,854 --> 04:32:27,756 >> FASCINATING STUDY THAT IS. 5910 04:32:27,756 --> 04:32:28,690 ONE OF THE SORT OF DIFFICULTIES 5911 04:32:28,690 --> 04:32:33,828 IN WORKING WITH OPSIN SS IF YOU 5912 04:32:33,828 --> 04:32:35,463 PROVIDE ENOUGH LIGHT, ENOUGH 5913 04:32:35,463 --> 04:32:37,132 PHOTONS OF ANY WAVELENGTH YOU 5914 04:32:37,132 --> 04:32:38,533 CAN STIMULATE ANY OPSIN. 5915 04:32:38,533 --> 04:32:39,868 SO WHEN I HEAR ABOUT STUDIES 5916 04:32:39,868 --> 04:32:42,103 LIKE THAT, I WONDER WHETHER YOU 5917 04:32:42,103 --> 04:32:43,271 MIGHT BE STIMULATING SOME OF 5918 04:32:43,271 --> 04:32:45,106 THESE OPSINS BECAUSE GREEN LIGHT 5919 04:32:45,106 --> 04:32:46,408 IS CLOSE ENOUGH TO SOME OF THESE 5920 04:32:46,408 --> 04:32:47,208 THAT YOU COULD. 5921 04:32:47,208 --> 04:32:49,043 HAD AND, YOU KNOW, TO BE HONEST, 5922 04:32:49,043 --> 04:32:50,011 I'M NOT ENTIRELY FAMILIAR WITH 5923 04:32:50,011 --> 04:32:51,246 THE DETAILS OF THAT STUDY. 5924 04:32:51,246 --> 04:32:52,647 I HAVE TO LOOK AT IT AGAIN. 5925 04:32:52,647 --> 04:32:54,282 BUT YEAH, IT'S A REALLY 5926 04:32:54,282 --> 04:32:55,216 INTERESTING PROPOSAL. 5927 04:32:55,216 --> 04:32:56,584 I MEAN, OF COURSE, WE THINK THAT 5928 04:32:56,584 --> 04:32:58,787 YOU MAY BE ABLE TO MODULATE PAIN 5929 04:32:58,787 --> 04:33:00,455 RESPONSES SIMPLY BY USING THE 5930 04:33:00,455 --> 04:33:02,624 PHOTON AS A DRUG. 5931 04:33:02,624 --> 04:33:08,263 >> THANK YOU. 5932 04:33:08,263 --> 04:33:12,167 >> SO WE HAVE TIME FOR ONE MORE 5933 04:33:12,167 --> 04:33:12,434 QUESTION. 5934 04:33:12,434 --> 04:33:15,570 >> DANA SMALL, MIGUEL 5935 04:33:15,570 --> 04:33:15,870 UNIVERSITY. 5936 04:33:15,870 --> 04:33:16,771 THANK YOU. 5937 04:33:16,771 --> 04:33:17,972 REALLY THOUGHT PROVOKING. 5938 04:33:17,972 --> 04:33:20,708 I'M WONDERING IF THE OPSIN 5939 04:33:20,708 --> 04:33:22,811 ADIPOSE SENSING MECHANISM MIGHT 5940 04:33:22,811 --> 04:33:25,313 BE RELATED TO THE NUTRIENT 5941 04:33:25,313 --> 04:33:26,915 PARTITIONING CIRCADIAN RHYTHMS. 5942 04:33:26,915 --> 04:33:28,950 >> ALMOST CERTAINLY THIS WHOLE 5943 04:33:28,950 --> 04:33:31,219 SYSTEM IS INTEGRATED WITH THE 5944 04:33:31,219 --> 04:33:32,854 CIRCADIAN CYCLE IN SOME WAY WE 5945 04:33:32,854 --> 04:33:34,923 DON'T CURRENTLY UNDERSTAND. 5946 04:33:34,923 --> 04:33:41,196 YOU KNOW, ONE OF THE FEATURES OF 5947 04:33:41,196 --> 04:33:43,498 NULL CELLS IS THAT THEY HAVE A 5948 04:33:43,498 --> 04:33:46,000 DIMINISHED AMPLITUDE CIRCADIAN 5949 04:33:46,000 --> 04:33:46,434 RHYTHM. 5950 04:33:46,434 --> 04:33:47,869 SO, YOU KNOW, MONITORING 5951 04:33:47,869 --> 04:33:50,738 INDIVIDUAL CELLS THAT EXPRESS 5952 04:33:50,738 --> 04:33:52,674 OPN3 YOU CAN SEE REDUCED 5953 04:33:52,674 --> 04:33:54,876 AMPLITUDE OSCILLATIONS SO THAT'S 5954 04:33:54,876 --> 04:33:56,211 ACTUALLY PRETTY LIKELY FOR THAT 5955 04:33:56,211 --> 04:33:57,078 PARTICULAR OPSIN. 5956 04:33:57,078 --> 04:33:58,079 >> THANK YOU. 5957 04:33:58,079 --> 04:34:00,348 >> I'M GOING ON TAKE A 5958 04:34:00,348 --> 04:34:02,350 PREROGATIVE ASK A QUESTION ON 5959 04:34:02,350 --> 04:34:04,118 BEHALF OF ALL THE GENETICISTS IN 5960 04:34:04,118 --> 04:34:05,620 THE AUDIENCE SNRIEF AN ANSWER 5961 04:34:05,620 --> 04:34:06,020 FOR YOU. 5962 04:34:06,020 --> 04:34:07,489 >> IN PARTICULAR, SHOULD WE GO 5963 04:34:07,489 --> 04:34:11,559 BACK TO HAMMERING ALL OF THESE 5964 04:34:11,559 --> 04:34:13,828 TWARGTS TEN MILLIGRAMS LIGHT TO 5965 04:34:13,828 --> 04:34:14,829 GET DEPOLARIZATION BLOCK? 5966 04:34:14,829 --> 04:34:17,532 >> YOU JUST NEED TO DO THE 5967 04:34:17,532 --> 04:34:19,834 WILD-TYPE CONTROL. 5968 04:34:19,834 --> 04:34:22,570 SO I THINK THESE ARE SLOW ACTING 5969 04:34:22,570 --> 04:34:22,904 OPSINS. 5970 04:34:22,904 --> 04:34:24,672 SO I MEAN, THE SORT OF TIME 5971 04:34:24,672 --> 04:34:25,874 SCALE OVER WHICH WE SEE 5972 04:34:25,874 --> 04:34:27,942 RESPONSES IS SORT OF FIVE, TEN, 5973 04:34:27,942 --> 04:34:29,143 TWENTY MINUTES. 5974 04:34:29,143 --> 04:34:30,545 SO WHEN YOU USE SOME OF THESE 5975 04:34:30,545 --> 04:34:33,948 REALLY FAST-ACTING OPTOGENETIC 5976 04:34:33,948 --> 04:34:35,149 TOOLS, I DON'T THINK ITS AN 5977 04:34:35,149 --> 04:34:35,483 ISSUE. 5978 04:34:35,483 --> 04:34:37,252 BUT YOU STILL NEED TO DO THE 5979 04:34:37,252 --> 04:34:37,685 WILD-TYPE CONTROL. 5980 04:34:37,685 --> 04:34:47,328 >> UNDERSTOOD. 5981 04:34:47,328 --> 04:34:49,397 SO BEHALF OF EVERYONE. 5982 04:34:49,397 --> 04:34:52,700 SO WE HAVE FIVE MINUTES LEFT. 5983 04:34:52,700 --> 04:34:54,536 I FIRST WANT TO MAKE SURE THAT 5984 04:34:54,536 --> 04:34:56,070 EVERYBODY WHO PRESENTED GETS A 5985 04:34:56,070 --> 04:34:57,805 CHANCE TO ANSWER ANY BURNING 5986 04:34:57,805 --> 04:35:04,078 QUESTIONS THAT YOU MIGHT HAVE. 5987 04:35:04,078 --> 04:35:06,147 IF YOU DO HAVE ANY, PLEASE STEP 5988 04:35:06,147 --> 04:35:06,614 UP. 5989 04:35:06,614 --> 04:35:06,814 OKAY. 5990 04:35:06,814 --> 04:35:07,582 WE HAVE ONE. 5991 04:35:07,582 --> 04:35:07,849 QUESTION. 5992 04:35:07,849 --> 04:35:11,953 >> QUICK QUESTION. 5993 04:35:11,953 --> 04:35:14,222 THE VISCERAL ORGANS, DO WE KNOW 5994 04:35:14,222 --> 04:35:20,428 IF THEY'RE INNERVATED BILY (?) 5995 04:35:20,428 --> 04:35:22,263 FIBERS -- IF THEY'RE INNERVATED 5996 04:35:22,263 --> 04:35:23,898 BY (?) FIBERS? 5997 04:35:23,898 --> 04:35:26,301 IN THE VISCERAL ORGANS. 5998 04:35:26,301 --> 04:35:27,669 >> DID YOU HEAR THE QUESTION? 5999 04:35:27,669 --> 04:35:29,904 YOU CAN REPEAT IT. 6000 04:35:29,904 --> 04:35:33,374 >> SO MY QUESTION WAS ABOUT THE 6001 04:35:33,374 --> 04:35:35,944 INNERVATION OF THE PIEZ02 IN THE 6002 04:35:35,944 --> 04:35:38,146 VISCERAL ORGANS, ARE THEY 6003 04:35:38,146 --> 04:35:43,585 INNERVATED BY (?) FINE RS OR -- 6004 04:35:43,585 --> 04:35:46,254 >> YOU HAVE ACTUALLY DONE SOME 6005 04:35:46,254 --> 04:35:49,324 SINGLE CELL RNA SEQ FROM FAT 6006 04:35:49,324 --> 04:35:51,526 INNERVATING NEURONS AND 6007 04:35:51,526 --> 04:35:53,895 REMARKABLY THEY HAVE EVERY 6008 04:35:53,895 --> 04:35:56,297 SUBCATEGORY MOLECULARLY DEFINED 6009 04:35:56,297 --> 04:35:58,499 AS SKIN INNERVATING NEURONS, SO 6010 04:35:58,499 --> 04:36:01,336 WE FIND THE MYELINATED P 6011 04:36:01,336 --> 04:36:03,104 UNMYELINATED, MULTIPLE TYPES OF 6012 04:36:03,104 --> 04:36:04,072 CGRP, EVERYTHING YOU HAVE IN THE 6013 04:36:04,072 --> 04:36:05,506 SKIN, EXCEPT FOR ONES THAT WERE 6014 04:36:05,506 --> 04:36:08,009 KNOWN TO BE VERY SPECIFIC ONES. 6015 04:36:08,009 --> 04:36:10,979 SO VAST MAJORITY OF THE DRG 6016 04:36:10,979 --> 04:36:12,347 SUBTYPES ALSO SEEM TO INNERVATE 6017 04:36:12,347 --> 04:36:13,348 THE FAT. 6018 04:36:13,348 --> 04:36:17,885 >> THANK YOU. 6019 04:36:17,885 --> 04:36:19,387 >> THANK YOU FOR A GREAT SESSION 6020 04:36:19,387 --> 04:36:20,488 TO ALL SPEAKERS. 6021 04:36:20,488 --> 04:36:25,526 SO MY QUESTION IS FOR RUI. 6022 04:36:25,526 --> 04:36:26,628 I'M -- DEVELOPMENTAL BIOLOGIST 6023 04:36:26,628 --> 04:36:28,830 AND YOUR FINDING THAT THE 6024 04:36:28,830 --> 04:36:30,665 TERMINAL SHAPE OR TERMINAL 6025 04:36:30,665 --> 04:36:32,867 MORPHOLOGY IS TO THE SPECIFIC TO 6026 04:36:32,867 --> 04:36:36,270 THE LAYERS BUT NOT TO THE 6027 04:36:36,270 --> 04:36:41,676 SENSORY SIGNAL TYPE. 6028 04:36:41,676 --> 04:36:43,044 CORRECTED? 6029 04:36:43,044 --> 04:36:43,811 >> YES. 6030 04:36:43,811 --> 04:36:46,114 >> SO MY QUESTION 6031 04:36:46,114 --> 04:36:48,516 DEVELOPMENTALLY IS, ARE YOU 6032 04:36:48,516 --> 04:36:51,052 PREDICTING THAT A SIMILAR TYPE 6033 04:36:51,052 --> 04:36:53,788 OF SIGNAL IS DICTATING THE 6034 04:36:53,788 --> 04:36:56,324 SHAPE, WHETHER THAT SIGNAL IS 6035 04:36:56,324 --> 04:36:59,994 FROM A CARDIAC MUSCLE VERSUS A 6036 04:36:59,994 --> 04:37:02,196 SMOOTH MUSCLE VERSUS A SKELETAL 6037 04:37:02,196 --> 04:37:03,765 MUSCLE VERSUS OTHER TISSUE? 6038 04:37:03,765 --> 04:37:06,701 >> THAT WOULD BE THE PREDICTION, 6039 04:37:06,701 --> 04:37:10,438 ALTHOUGH WE HAVE NO DATD ON IT 6040 04:37:10,438 --> 04:37:14,375 YET, BUT THAT'S SOMETHING WE ARE 6041 04:37:14,375 --> 04:37:17,645 THINKING OF, THAT THE TERMINAL 6042 04:37:17,645 --> 04:37:19,280 STRUCTURE, AT LEAST THE 6043 04:37:19,280 --> 04:37:20,948 CROSS-TERMINAL STRUCTURES ARE 6044 04:37:20,948 --> 04:37:22,350 FORMED BECAUSE OF THEIR 6045 04:37:22,350 --> 04:37:23,985 INTERACTIONS WITH THE LOCAL 6046 04:37:23,985 --> 04:37:24,419 ENVIRONMENT. 6047 04:37:24,419 --> 04:37:25,853 SO THAT'S HELPING THEM TO ADAPT 6048 04:37:25,853 --> 04:37:28,690 TO THE LOCAL ENVIRONMENT. 6049 04:37:28,690 --> 04:37:30,324 AND SO WHAT TYPE OF STIMULUS 6050 04:37:30,324 --> 04:37:31,993 THEY'RE ACTUALLY SENSING THAT, 6051 04:37:31,993 --> 04:37:33,628 DEPENDS ON THE RECEPTORS 6052 04:37:33,628 --> 04:37:36,330 EXPRESSED, AND MAYBE THE OTHER 6053 04:37:36,330 --> 04:37:38,866 STRUCTURES THAT THE RECEPTORS 6054 04:37:38,866 --> 04:37:39,300 WILL FORM. 6055 04:37:39,300 --> 04:37:39,867 >> GREAT. 6056 04:37:39,867 --> 04:37:41,969 THANK YOU. 6057 04:37:41,969 --> 04:37:43,204 >> THANK YOU VERY MUCH TO ALL 6058 04:37:43,204 --> 04:37:45,740 THE SPEAKERS. 6059 04:37:45,740 --> 04:37:48,576 RICHARD, THIS QUESTION IS FOR 6060 04:37:48,576 --> 04:37:48,743 YOU. 6061 04:37:48,743 --> 04:37:49,811 WITH REGARDS TO SINCE YOU 6062 04:37:49,811 --> 04:37:53,081 BROUGHT UP THE WORLD VIEW 6063 04:37:53,081 --> 04:37:55,717 PICTURE, I'M CURIOUS, SOMETHING 6064 04:37:55,717 --> 04:37:57,652 THAT YOU MAY OR MAY NOT HAVE 6065 04:37:57,652 --> 04:37:59,187 BEEN THINKING ABOUT OR I'M 6066 04:37:59,187 --> 04:38:00,321 GUESSING YOU HAVE OR SOMEONE HAS 6067 04:38:00,321 --> 04:38:02,924 ASKED THIS QUESTION BEFORE, IN 6068 04:38:02,924 --> 04:38:04,792 THE CONTEXT OF ARTIFICIAL BLUE 6069 04:38:04,792 --> 04:38:06,661 LIGHT AND ALL THAT WE'RE EXPOSED 6070 04:38:06,661 --> 04:38:10,798 TO AND HOW MUCH TIME WE SPEND 6071 04:38:10,798 --> 04:38:12,567 BEING EXPOSED TO ARTIFICIAL BLUE 6072 04:38:12,567 --> 04:38:13,701 LIGHT, DO YOU HAVE ANY THOUGHTS 6073 04:38:13,701 --> 04:38:17,271 WITH REGARDS TO HOW THIS IS 6074 04:38:17,271 --> 04:38:19,774 CHANGING THE REGULATION OF 6075 04:38:19,774 --> 04:38:22,310 OPSINS WITHIN THE BRAIN AND HOW 6076 04:38:22,310 --> 04:38:25,580 THAT COULD IMPACT IN A SORT OF 6077 04:38:25,580 --> 04:38:29,851 GENETIC, HE JCT WAY -- HE VECT 6078 04:38:29,851 --> 04:38:37,058 WAY -- EPIJ GE -- EPIGENETIC 6079 04:38:37,058 --> 04:38:41,429 BETWEEN HUMANS? 6080 04:38:41,429 --> 04:38:44,632 >>S INTERESTING FOR HAD ARE 6081 04:38:44,632 --> 04:38:46,267 DEFICIENT IN HUMANS, THE LEAD 6082 04:38:46,267 --> 04:38:49,337 DEFICIENT DISEASE IS ACTUALLY 6083 04:38:49,337 --> 04:38:51,105 MYOPIA, SO I WOULD GUESS 30% OF 6084 04:38:51,105 --> 04:38:52,840 THE AUDIENCE PROBABLY HAS 6085 04:38:52,840 --> 04:38:53,708 MYOPIA, PROBABLY ABOUT RIGHT, 6086 04:38:53,708 --> 04:38:55,810 AND WE THINK WE KNOW WHY THAT IS 6087 04:38:55,810 --> 04:38:56,844 NOW, BASICALLY BECAUSE WE LIVE 6088 04:38:56,844 --> 04:38:58,179 IN A LIGHTING ENVIRONMENT WHERE 6089 04:38:58,179 --> 04:39:00,915 WE'RE NOT STIMULATING OPN5 IN 6090 04:39:00,915 --> 04:39:03,217 THE RETINA AND TURNS OUT THAT 6091 04:39:03,217 --> 04:39:05,987 OPN5 IS REALLY IMPORTANT FOR 6092 04:39:05,987 --> 04:39:07,021 SUPPRESSING ABNORMAL ELONGATION 6093 04:39:07,021 --> 04:39:11,125 OF THE EYE AND, YOU KNOW, THAT'S 6094 04:39:11,125 --> 04:39:11,359 MYOPIA. 6095 04:39:11,359 --> 04:39:13,961 WHEN THE EYE ELONGATES 6096 04:39:13,961 --> 04:39:15,596 ABNORMALLY, YOU'RE NEARSIGHTED. 6097 04:39:15,596 --> 04:39:16,697 SO THAT'S -- THE EVIDENCE OF 6098 04:39:16,697 --> 04:39:19,400 THAT NOW IS REALLY, REALLY 6099 04:39:19,400 --> 04:39:19,634 STRONG. 6100 04:39:19,634 --> 04:39:22,403 SO OBVIOUSLY WHAT WE'RE DOING 6101 04:39:22,403 --> 04:39:23,905 THERE IS GETTING SERIOUS ABOUT 6102 04:39:23,905 --> 04:39:25,907 CREATING LIGHTING SYSTEMS THAT 6103 04:39:25,907 --> 04:39:30,044 DO PRODUCE THE VIOLET PHOTONS TO 6104 04:39:30,044 --> 04:39:30,678 STIMULATE OPN5. 6105 04:39:30,678 --> 04:39:32,013 YOU CAN SOLVE THIS PROBLEM BY 6106 04:39:32,013 --> 04:39:33,781 GOING OUTSIDE FOR A COUPLE OF 6107 04:39:33,781 --> 04:39:34,849 HOURS EVERY DAY, SO YOU DON'T 6108 04:39:34,849 --> 04:39:36,083 NEED ONE OF THESE LIGHTING 6109 04:39:36,083 --> 04:39:38,052 SYSTEM, BUT THAT'S THE SORT OF 6110 04:39:38,052 --> 04:39:39,220 CAUSATION ARGUMENT THAT'S 6111 04:39:39,220 --> 04:39:39,487 EMERGING. 6112 04:39:39,487 --> 04:39:41,756 BUT THERE ARE VERY SIMILAR 6113 04:39:41,756 --> 04:39:43,191 CAUSATION ARGUMENT FOR METABOLIC 6114 04:39:43,191 --> 04:39:44,158 DISEASE, OBVIOUSLY I'VE SHOWN 6115 04:39:44,158 --> 04:39:46,794 YOU WHAT OPN5 CAN DO IN ENERGY 6116 04:39:46,794 --> 04:39:48,629 HOMOEOSTASIS, THAT'S VERY LIKELY 6117 04:39:48,629 --> 04:39:50,932 TO BE CONSERVED IN HUMANS, SO WE 6118 04:39:50,932 --> 04:39:53,367 ARE THINKING THAT, YOU KNOW, 6119 04:39:53,367 --> 04:39:55,203 THERE'S THIS ACCELERATING 6120 04:39:55,203 --> 04:39:57,605 PREVALENCE OF METABOLIC SYNDROME 6121 04:39:57,605 --> 04:39:59,473 AND DIABETES, MUCH LIKE THERE'S 6122 04:39:59,473 --> 04:40:01,676 AN ACCELERATING PREVALENCE OF 6123 04:40:01,676 --> 04:40:03,411 MYOPIA, SO THERE'S THIS REALLY 6124 04:40:03,411 --> 04:40:04,712 INTERESTING QUESTION ABOUT THOSE 6125 04:40:04,712 --> 04:40:06,814 DISEASES THAT ARE ALSO A RESULT 6126 04:40:06,814 --> 04:40:09,784 OF DEFICIENT LIGHTING SYSTEMS. 6127 04:40:09,784 --> 04:40:10,518 SO YEAH. 6128 04:40:10,518 --> 04:40:14,922 >> THANK YOU. 6129 04:40:14,922 --> 04:40:21,529 >> GREAT TALKS. 6130 04:40:21,529 --> 04:40:23,898 ASSOCIATE PROCEED SES SORE FROM 6131 04:40:23,898 --> 04:40:26,167 THE UNIVERSITY OF MARYLAND 6132 04:40:26,167 --> 04:40:27,768 MARYLAND BALTIMORE. 6133 04:40:27,768 --> 04:40:29,170 INTERESTING TALK. 6134 04:40:29,170 --> 04:40:30,238 I HAVE A CLARIFICATION QUESTION. 6135 04:40:30,238 --> 04:40:33,140 I WAS USED TO THINKING ABOUT 6136 04:40:33,140 --> 04:40:35,042 KIND OF THE MAPPING OF BODY TO, 6137 04:40:35,042 --> 04:40:38,913 YOU KNOW, ASCENDING NERVES AS 6138 04:40:38,913 --> 04:40:42,650 LIKE A SOMATOPIC MAP BUT YOU'RE 6139 04:40:42,650 --> 04:40:44,218 ALSO SHOWING THERE'S EN CODING 6140 04:40:44,218 --> 04:40:46,520 OF THE SPACE -- ENCODING OF THE 6141 04:40:46,520 --> 04:40:48,256 SPACE, WHICH ORGAN IS INNERVATED 6142 04:40:48,256 --> 04:40:50,124 AND WHAT PART OF THE ORGAN BY 6143 04:40:50,124 --> 04:40:51,092 THESE GENETIC EXPRESSION 6144 04:40:51,092 --> 04:40:52,093 DIFFERENCES, THAT SEEMS LIKE 6145 04:40:52,093 --> 04:40:54,729 KIND OF REDUNDANT, LIKE COULDN'T 6146 04:40:54,729 --> 04:40:59,100 THE NERVES JUST HAVE A SOMATOPIC 6147 04:40:59,100 --> 04:41:00,568 MAP THAT GOES FROM ONE PLACE IN 6148 04:41:00,568 --> 04:41:01,936 THE PERIPHERY TO ONE PLACE IN 6149 04:41:01,936 --> 04:41:03,237 THE SPINAL CORD OR IN THE 6150 04:41:03,237 --> 04:41:05,640 BRAINSTEM AND YOU WOULDN'T NEED 6151 04:41:05,640 --> 04:41:07,408 THESE DIFFERENCES? 6152 04:41:07,408 --> 04:41:09,277 SO THAT'S JUST A CLARIFICATION. 6153 04:41:09,277 --> 04:41:12,213 IS THIS A SENSE OF LIKE A 6154 04:41:12,213 --> 04:41:13,214 REDUNDANCY THAT WE'RE SEEING? 6155 04:41:13,214 --> 04:41:15,616 >> THAT IS A GREAT QUESTION, AND 6156 04:41:15,616 --> 04:41:21,889 SO WE KNOW THAT THERE IS A MAP 6157 04:41:21,889 --> 04:41:22,957 IN NTS. 6158 04:41:22,957 --> 04:41:24,292 THE QUESTION IS WHETHER THERE IS 6159 04:41:24,292 --> 04:41:26,594 A MAP IN THE VAGUE VAGUS NERVE 6160 04:41:26,594 --> 04:41:28,996 AND SO FAR PREVIOUS STUDIES 6161 04:41:28,996 --> 04:41:31,098 INCLUDING SOME OF OURS SHOW THAT 6162 04:41:31,098 --> 04:41:36,537 THERE'S NOT A VISCERAL MAP IN 6163 04:41:36,537 --> 04:41:37,505 THE -- SO ONE OF THE 6164 04:41:37,505 --> 04:41:38,105 POSSIBILITIES, COULD BE LIKE 6165 04:41:38,105 --> 04:41:41,008 YOU'RE RATE, THE VALG -- YOU'RE 6166 04:41:41,008 --> 04:41:42,677 RIGHT, THE VAGUS NERVE SERVES 6167 04:41:42,677 --> 04:41:43,978 APPEARS THE CONNECT TORDZ, BASIC 6168 04:41:43,978 --> 04:41:45,613 YOU CAN SEE THEM APPEARS THE 6169 04:41:45,613 --> 04:41:47,581 WIRES, THEY JUST CONNECT A TO B 6170 04:41:47,581 --> 04:41:49,016 AND ONCE IT'S CONNECTED, YOU'RE 6171 04:41:49,016 --> 04:41:49,717 DONE, RIGHT? 6172 04:41:49,717 --> 04:41:51,052 YOU DON'T NEED TO KNOW WHICH ONE 6173 04:41:51,052 --> 04:41:52,119 IS CONNECT TO DO WHICH BECAUSE 6174 04:41:52,119 --> 04:41:53,220 IT'S ALREADY THE CONNECTION IS 6175 04:41:53,220 --> 04:41:54,422 ALREADY SET UP. 6176 04:41:54,422 --> 04:41:56,490 BUT THAT'S NOT WHAT WE OBSERVED. 6177 04:41:56,490 --> 04:41:57,925 ACTUALLY, WE ARE ALSO VERY 6178 04:41:57,925 --> 04:41:59,126 SURPRISED TO SEE THIS. 6179 04:41:59,126 --> 04:42:00,661 AND THE MORE WE THINK ABOUT IT, 6180 04:42:00,661 --> 04:42:02,697 THE MORE WE FEEL LIKE THERE 6181 04:42:02,697 --> 04:42:04,265 MIGHT BE A BIOLOGICAL REASON FOR 6182 04:42:04,265 --> 04:42:07,868 T OF COURSE, WE DON'T HAVE ANY 6183 04:42:07,868 --> 04:42:09,637 EXPERIMENT DATA TO BACK UP. 6184 04:42:09,637 --> 04:42:11,372 ONE POSSIBILITY IS BECAUSE THESE 6185 04:42:11,372 --> 04:42:13,341 NEURONS DON'T REGENERATE AND YOU 6186 04:42:13,341 --> 04:42:16,077 DO HAVE DAMAGE OF THE PERIPHERY 6187 04:42:16,077 --> 04:42:17,812 NERVES, VERY COMMONLY, AND THEY 6188 04:42:17,812 --> 04:42:19,447 WILL DO REGENERATION TO A 6189 04:42:19,447 --> 04:42:20,348 CERTAIN DEGREE. 6190 04:42:20,348 --> 04:42:22,516 ONE POSSIBILITY IS LIKE THESE 6191 04:42:22,516 --> 04:42:25,019 NEURONS THAT ARE AT THIS STAGE 6192 04:42:25,019 --> 04:42:26,253 STILL KEEP THAT SPATIAL 6193 04:42:26,253 --> 04:42:27,121 INFORMATION LIKE AND WILL 6194 04:42:27,121 --> 04:42:28,189 POTENTIALLY BECAUSE THEY DO NEED 6195 04:42:28,189 --> 04:42:30,391 TO RECOGNIZE THE SAME SPOT 6196 04:42:30,391 --> 04:42:30,591 AGAIN. 6197 04:42:30,591 --> 04:42:32,360 SO THERE'S ONE EXPERIMENT WE DO 6198 04:42:32,360 --> 04:42:33,627 TALK ABOUT, WE HAVEN'T STARTED 6199 04:42:33,627 --> 04:42:37,431 TO DO IT YET, IS TO DAMAGE THOSE 6200 04:42:37,431 --> 04:42:39,600 NEURONS WITH A GENETIC LABEL 6201 04:42:39,600 --> 04:42:40,701 POPULATIONS AND REALLY SEE IF 6202 04:42:40,701 --> 04:42:42,570 THOSE NEURONS WILL GO BACK TO 6203 04:42:42,570 --> 04:42:44,005 THE SAME LOCATION OR DO THEY 6204 04:42:44,005 --> 04:42:46,073 STILL KNOW WHERE THEY SHOULD GO. 6205 04:42:46,073 --> 04:42:49,243 SO I THINK THAT IS A POSSIBILITY 6206 04:42:49,243 --> 04:42:51,112 THAT MAKES WHY THESE STIMULUS 6207 04:42:51,112 --> 04:42:53,714 STILL NEED TO KEEP THOSE 6208 04:42:53,714 --> 04:42:54,015 INFORMATION. 6209 04:42:54,015 --> 04:42:55,583 >> MAY I ASK A FOLLOW-UP? 6210 04:42:55,583 --> 04:42:55,916 >> PLEASE. 6211 04:42:55,916 --> 04:42:59,653 >> OKAY, THANK YOU. 6212 04:42:59,653 --> 04:43:01,522 SO THEN THAT IS A GREAT ANSWER, 6213 04:43:01,522 --> 04:43:02,289 THANK YOU. 6214 04:43:02,289 --> 04:43:05,459 THEN THE FOLLOW-UP IS, IS IT 6215 04:43:05,459 --> 04:43:07,328 THAT ALL OF THESE GENETIC 6216 04:43:07,328 --> 04:43:09,196 EXPRESSION DIFFERENCES THAT YOU 6217 04:43:09,196 --> 04:43:13,768 OBSERVE THAT KIND OF REPLACE THE 6218 04:43:13,768 --> 04:43:14,902 SOMATOTOPIC MAP THAT IS THERE IN 6219 04:43:14,902 --> 04:43:16,871 OTHER PART OF THE NERVOUS SYSTEM 6220 04:43:16,871 --> 04:43:18,272 IS ONLY THERE TO MODULATE THE 6221 04:43:18,272 --> 04:43:21,442 FIRING OF THOSE NERVES? 6222 04:43:21,442 --> 04:43:23,210 THROUGH ION CHANNELS OR THE WAY 6223 04:43:23,210 --> 04:43:25,079 THAT THE NEURONS RESPOND? 6224 04:43:25,079 --> 04:43:30,084 IS THAT BASICALLY INSTEAD OF THE 6225 04:43:30,084 --> 04:43:31,185 SOMATOTOPIC MAP KNOWING THAT ONE 6226 04:43:31,185 --> 04:43:33,054 NERVE GOES FROM PLACE A TO PLACE 6227 04:43:33,054 --> 04:43:35,156 B EACH TIME, IT'S THAT THE 6228 04:43:35,156 --> 04:43:37,124 FIRING PATTERN OR SOMETHING IS 6229 04:43:37,124 --> 04:43:40,694 ENCODING THE SOMATOTOPIC MAP? 6230 04:43:40,694 --> 04:43:41,796 >> THAT IS AN INTERESTING 6231 04:43:41,796 --> 04:43:42,063 QUESTION. 6232 04:43:42,063 --> 04:43:44,098 WE HAVEN'T STARTED TO LOOK AT 6233 04:43:44,098 --> 04:43:45,533 THAT BECAUSE OF THE TOOLS WE ARE 6234 04:43:45,533 --> 04:43:49,937 USING IS BASICALLY IMAGING THAT 6235 04:43:49,937 --> 04:43:51,439 DOES GIVE SOME SPIKING 6236 04:43:51,439 --> 04:43:53,541 INFORMATION FREQUENCY BUT NOT 6237 04:43:53,541 --> 04:43:55,042 EXACTLY RECAPITULATING THE 6238 04:43:55,042 --> 04:43:56,210 ELECTRICAL SIGNALS. 6239 04:43:56,210 --> 04:43:58,012 ON THE OTHER HAND, MOST OF THE 6240 04:43:58,012 --> 04:44:00,181 GENES WE ACTUALLY SEE FROM THOSE 6241 04:44:00,181 --> 04:44:03,250 GENE MODULES FOLLOW ORGAN CELL, 6242 04:44:03,250 --> 04:44:05,019 TISSUE LAYERS R THE GENES 6243 04:44:05,019 --> 04:44:11,125 INVOLVED IN AXON GUIDANCE AND 6244 04:44:11,125 --> 04:44:14,195 NEURON ATTRACTIVE CUES, SO I 6245 04:44:14,195 --> 04:44:16,497 DON'T THINK THAT THAT KIND OF 6246 04:44:16,497 --> 04:44:18,365 SUPPORTS THE IDEA THAT IT'S USED 6247 04:44:18,365 --> 04:44:19,867 TO MAINTAIN THIS INTERACTION 6248 04:44:19,867 --> 04:44:24,905 WITH LOCAL TISSUES, IF THAT 6249 04:44:24,905 --> 04:44:25,606 ANSWERS YOUR QUESTION. 6250 04:44:25,606 --> 04:44:26,207 >> YEAH. 6251 04:44:26,207 --> 04:44:27,208 THANK YOU VERY MUCH. 6252 04:44:27,208 --> 04:44:27,875 REALLY FASCINATING. 6253 04:44:27,875 --> 04:44:29,543 >> NOW WE'LL OPEN UP THE FLOOR 6254 04:44:29,543 --> 04:44:30,845 TO ALL THE STUDENTS WHO HAVE 6255 04:44:30,845 --> 04:44:36,317 BURNING QUESTIONS. 6256 04:44:36,317 --> 04:44:36,650 OKAY. 6257 04:44:36,650 --> 04:44:37,852 AND IF THAT'S NOT HAPPENING, 6258 04:44:37,852 --> 04:44:40,020 THEN I'LL JUST ASK ONE LAST ONE. 6259 04:44:40,020 --> 04:44:41,322 IS THERE ONE? 6260 04:44:41,322 --> 04:44:42,223 OH, FANTASTIC. 6261 04:44:42,223 --> 04:44:52,099 MUCH BETTER. 6262 04:44:52,099 --> 04:44:54,235 >> THIS IS A QUESTION FOR THE 6263 04:44:54,235 --> 04:44:54,902 WHOLE PANEL. 6264 04:44:54,902 --> 04:44:57,738 I JUST WANT TO KNOW IF THE LINK 6265 04:44:57,738 --> 04:45:01,008 BETWEEN THE SOMATOSENSORY 6266 04:45:01,008 --> 04:45:05,746 PATHWAY AND THE SYMPATHETIC, 6267 04:45:05,746 --> 04:45:08,382 PARASYMPATHETIC, IT'S WHAT'S 6268 04:45:08,382 --> 04:45:10,718 UNDERLYING INTEROCEPTION AS IN 6269 04:45:10,718 --> 04:45:13,420 WE HAVE INTEGRATING SYSTEMS IN 6270 04:45:13,420 --> 04:45:16,924 THE BRAINSTEM THAT HAVE THE 6271 04:45:16,924 --> 04:45:18,425 MEANS OF RECEIVING THE SIGNAL 6272 04:45:18,425 --> 04:45:22,496 AND THEN RESPONDING TO THAT 6273 04:45:22,496 --> 04:45:22,863 SIGNAL. 6274 04:45:22,863 --> 04:45:25,432 SO NOW THAT WE HAVE HUMAN 6275 04:45:25,432 --> 04:45:26,467 INTERVENTIONS THAT ARE SEEKING 6276 04:45:26,467 --> 04:45:31,372 TO DO THAT, I WONDER IF IT'S 6277 04:45:31,372 --> 04:45:33,774 WORTH DELVING INTO THE 6278 04:45:33,774 --> 04:45:35,342 INTERACTION BETWEEN THESE TWO 6279 04:45:35,342 --> 04:45:37,845 SYSTEMS AND IF THAT WOULD INFORM 6280 04:45:37,845 --> 04:45:40,114 A LITTLE BIT ABOUT WHAT THE 6281 04:45:40,114 --> 04:45:43,517 PREVIOUS QUESTION WAS ABOUT HOW 6282 04:45:43,517 --> 04:45:45,920 WE GENERATE THIS VERY SPECIFIC 6283 04:45:45,920 --> 04:45:51,392 RESPONSES TO THIS WIDELY VARIANT 6284 04:45:51,392 --> 04:45:52,359 STIMULI. 6285 04:45:52,359 --> 04:45:54,461 >> WERE YOU TALKING ABOUT 6286 04:45:54,461 --> 04:45:55,162 TEMPERATURE? 6287 04:45:55,162 --> 04:45:58,199 IS THAT WHAT YOU STARTED OFF 6288 04:45:58,199 --> 04:46:00,267 SAYING? 6289 04:46:00,267 --> 04:46:01,569 >> I AMINE ALONG WITH 6290 04:46:01,569 --> 04:46:03,137 TEMPERATURE BURKT THE MECHANICAL 6291 04:46:03,137 --> 04:46:06,207 RESPONSES THAT ARDEM WAS TALKING 6292 04:46:06,207 --> 04:46:07,541 ABOUT, THE CHEMICAL RESPONSE 6293 04:46:07,541 --> 04:46:09,577 THAT IS HAPPEN IN THE STOMACH 6294 04:46:09,577 --> 04:46:13,514 AND IN THE MUSCLES, YEAH, THIS 6295 04:46:13,514 --> 04:46:13,814 IS WIDE. 6296 04:46:13,814 --> 04:46:16,250 >> SO ARE YOU ASKING FOR US TO 6297 04:46:16,250 --> 04:46:19,553 EXPLAIN HOW THAT ALL GETS 6298 04:46:19,553 --> 04:46:20,921 INTEGRATED? 6299 04:46:20,921 --> 04:46:22,523 >> YES, AND -- 6300 04:46:22,523 --> 04:46:25,226 >> I'M WITH YOU. 6301 04:46:25,226 --> 04:46:25,426 RIGHT? 6302 04:46:25,426 --> 04:46:26,126 >> RIGHT. 6303 04:46:26,126 --> 04:46:29,597 >> THAT'S WHY WE'RE ALL HERE. 6304 04:46:29,597 --> 04:46:29,797 RIGHT. 6305 04:46:29,797 --> 04:46:32,333 >> I CAN JUST SIMPLY SAY FOR OUR 6306 04:46:32,333 --> 04:46:34,535 SYSTEM, YU HAS FOUND THAT I TOLD 6307 04:46:34,535 --> 04:46:36,403 YOU THAT THE SENSORY SEEMS TO BE 6308 04:46:36,403 --> 04:46:40,441 ACTING AS A BLOCK OF FEEDBACK TO 6309 04:46:40,441 --> 04:46:42,943 THE SYMPATHETIC, WE KNOW THE 6310 04:46:42,943 --> 04:46:43,877 SYMPATHETIC SIGNAL IS REQUIRED 6311 04:46:43,877 --> 04:46:46,680 FOR THE EFFECT OF THE DRG 6312 04:46:46,680 --> 04:46:47,781 ABLATION FOR EXAMPLE, BUT WE 6313 04:46:47,781 --> 04:46:49,850 HAVE NO IDEA WHERE IN THE 6314 04:46:49,850 --> 04:46:51,585 CIRCUITRY THE COMMUNICATION IS 6315 04:46:51,585 --> 04:46:53,687 HAPPENING. 6316 04:46:53,687 --> 04:46:54,755 SO I THINK FOR THAT, I THINK 6317 04:46:54,755 --> 04:46:57,958 THIS IS A GREAT SYSTEM TO START 6318 04:46:57,958 --> 04:47:00,261 LOOKING AT AS PEOPLE LIKE RUI 6319 04:47:00,261 --> 04:47:02,229 AND OTHERS ARE LOOKING AT 6320 04:47:02,229 --> 04:47:03,864 SENDING PATHWAYS AND HOW THIS 6321 04:47:03,864 --> 04:47:06,133 AND WHAT LEVELS IS THERE 6322 04:47:06,133 --> 04:47:08,135 COMMUNICATION WITH THE AUTONOMIC 6323 04:47:08,135 --> 04:47:09,436 NERVOUS SYSTEM IS AN INTERESTING 6324 04:47:09,436 --> 04:47:10,537 QUESTION INDEED. 6325 04:47:10,537 --> 04:47:12,273 >> CAN I FOLLOW UP ON THAT AS 6326 04:47:12,273 --> 04:47:12,506 WELL? 6327 04:47:12,506 --> 04:47:14,475 SO MY OTHER HALF OF MY LIFE IS 6328 04:47:14,475 --> 04:47:15,676 STUDYING THE SENSORY NERVES FROM 6329 04:47:15,676 --> 04:47:17,077 THE KIDNEY TO THE BRAIN AND WHAT 6330 04:47:17,077 --> 04:47:17,645 THEY DO. 6331 04:47:17,645 --> 04:47:21,148 THEY DO MODULATE, SYMPATHETIC 6332 04:47:21,148 --> 04:47:22,249 ACTIVITY, BUT FOLKS IN THE LAB 6333 04:47:22,249 --> 04:47:25,319 THAT ARE HERE ARE FINDING THAT 6334 04:47:25,319 --> 04:47:27,721 SIGNALS THAT REGULATE THIRST, 6335 04:47:27,721 --> 04:47:29,590 SALT APPETITE, HORMONE RELEASE, 6336 04:47:29,590 --> 04:47:31,191 EVERY ORGAN IS TALKING TO THE 6337 04:47:31,191 --> 04:47:32,426 BRAIN ALL THE TIME. 6338 04:47:32,426 --> 04:47:32,960 RIGHT? 6339 04:47:32,960 --> 04:47:35,262 TO MODULATE, NOT JUST AUTONOMIC 6340 04:47:35,262 --> 04:47:36,597 BUT ALL THESE BEHAVIORAL 6341 04:47:36,597 --> 04:47:37,898 RESPONSES WHICH I THINK IS 6342 04:47:37,898 --> 04:47:39,199 PRETTY FASCINATING BUT TAKE A 6343 04:47:39,199 --> 04:47:41,702 WHILE TO FIGURE OUT. 6344 04:47:41,702 --> 04:47:42,503 >> ALL RIGHT. 6345 04:47:42,503 --> 04:47:44,138 I'M GOING TO END UP WITH ONE 6346 04:47:44,138 --> 04:47:45,239 LAST QUESTION FOR THE WHOLE 6347 04:47:45,239 --> 04:47:46,407 PANEL HERE. 6348 04:47:46,407 --> 04:47:48,175 I THINK WHAT WE'VE HEARD THIS 6349 04:47:48,175 --> 04:47:50,711 AFTERNOON IS PRETTY AMAZING 6350 04:47:50,711 --> 04:47:53,447 DIVERSITY OF INPUTS THAT OFTEN 6351 04:47:53,447 --> 04:47:55,215 HAVE SPECIFICATION AT THE LEVEL 6352 04:47:55,215 --> 04:47:59,353 OF TOPOGRAPHY AND LAYER WITHIN 6353 04:47:59,353 --> 04:48:02,122 AN ORGAN MAPPING ONTO DISTINCT 6354 04:48:02,122 --> 04:48:03,857 MOLECULAR SIGNATURES, SO I GUESS 6355 04:48:03,857 --> 04:48:06,760 MY QUESTION FOR ALL OF YOU IS, 6356 04:48:06,760 --> 04:48:08,662 YOU KNOW, IS THE VAGUS NERVE 6357 04:48:08,662 --> 04:48:10,431 STIMULATION OF THE FUTURE GOING 6358 04:48:10,431 --> 04:48:13,067 TO BE TARGETABLE TO SPECIFIC 6359 04:48:13,067 --> 04:48:15,035 CELL TYPES INNERVATING SPECIFIC 6360 04:48:15,035 --> 04:48:17,004 ORGANS AND WHAT ARE THE 6361 04:48:17,004 --> 04:48:22,343 PROSPECTS FOR THAT? 6362 04:48:22,343 --> 04:48:24,211 I CAN START WITH -- I'LL MAKE IT 6363 04:48:24,211 --> 04:48:24,878 MORE SPECIFIC. 6364 04:48:24,878 --> 04:48:26,180 I'LL START WITH RUI. 6365 04:48:26,180 --> 04:48:28,282 WHEN YOU LOOK AT YOUR SCWERNSING 6366 04:48:28,282 --> 04:48:30,451 DATA, ARE WE HAVING TO TARGET -- 6367 04:48:30,451 --> 04:48:31,752 SEQUENCING DATA, ARE WE HAVING 6368 04:48:31,752 --> 04:48:33,821 TO TARGET FIVE DIFFERENT 6369 04:48:33,821 --> 04:48:35,689 PROMOTERS IN ORDER TO GAIN THAT 6370 04:48:35,689 --> 04:48:37,891 SPECIFICITY THAT YOU SEE IN YOUR 6371 04:48:37,891 --> 04:48:40,060 UMAP PLOT OR IS THERE A SIMPLER 6372 04:48:40,060 --> 04:48:42,396 TARGETING OF JUST A FEW UNIQUE 6373 04:48:42,396 --> 04:48:42,596 GENES? 6374 04:48:42,596 --> 04:48:46,100 >> WELL, FROM THE MOUSE POINT OF 6375 04:48:46,100 --> 04:48:49,937 VIEW -- AND FROM A SINGLE CELL 6376 04:48:49,937 --> 04:48:52,973 POINT OF VIEW, YOU JUST NEED ONE 6377 04:48:52,973 --> 04:48:54,508 PROMOTER TO TARGET AND THERE ARE 6378 04:48:54,508 --> 04:48:55,709 SOME NEURON POPULATIONS THAT YOU 6379 04:48:55,709 --> 04:48:59,113 DO NEED MULTIPLE GENES TO 6380 04:48:59,113 --> 04:48:59,346 TARGET. 6381 04:48:59,346 --> 04:49:03,050 BUT HOW DOES THIS TRANSLATE TO 6382 04:49:03,050 --> 04:49:05,119 HUMAN APPLICATIONS IS STILL A 6383 04:49:05,119 --> 04:49:05,486 QUESTION. 6384 04:49:05,486 --> 04:49:08,722 I MEAN, I DO BELIEVE THAT THERE 6385 04:49:08,722 --> 04:49:12,359 ARE THE NEURONS FROM DIFFERENT 6386 04:49:12,359 --> 04:49:17,498 SUBTYPES DO HAVE DIFFERENT 6387 04:49:17,498 --> 04:49:19,767 THRESHOLD FOR ELECTRICAL 6388 04:49:19,767 --> 04:49:21,635 STIMULATIONS, BUT ON THE OTHER 6389 04:49:21,635 --> 04:49:23,070 HAND, WHETHER THAT THRESHOLD 6390 04:49:23,070 --> 04:49:25,038 DIFFERENCE IS BIG ENOUGH THAT WE 6391 04:49:25,038 --> 04:49:27,775 CAN SOMEHOW TARGET IT IN HUMAN 6392 04:49:27,775 --> 04:49:30,611 IS A QUESTION. 6393 04:49:30,611 --> 04:49:33,680 ANOTHER THING I'M ACTUALLY 6394 04:49:33,680 --> 04:49:37,217 THINKING ABOUT IS IF IT'S 6395 04:49:37,217 --> 04:49:44,425 FEASIBLE TO COMBINE THE 6396 04:49:44,425 --> 04:49:46,160 ELECTRICAL PARAMETERS WITH 6397 04:49:46,160 --> 04:49:47,795 BRANCH SPECIFIC STIMULATION. 6398 04:49:47,795 --> 04:49:51,432 I THINK THAT MAY GIVE A BETTER 6399 04:49:51,432 --> 04:49:55,769 EFFICACY OF THE VAGUS NERVE 6400 04:49:55,769 --> 04:49:56,370 STIMULATION IN THE FUTURE. 6401 04:49:56,370 --> 04:49:58,105 >> IN TERMS OF THE HUMAN WORK, 6402 04:49:58,105 --> 04:49:59,406 THE IDEA WITH THAT STUDY THAT 6403 04:49:59,406 --> 04:50:01,408 WE'RE DOING IS TO GENERATE A 6404 04:50:01,408 --> 04:50:03,577 HUGE DATASET AND THEN DO 6405 04:50:03,577 --> 04:50:05,446 ADVANCED MODELING TO LOOK AT 6406 04:50:05,446 --> 04:50:06,613 STIMULUS PARAMETERS SO WE CAN 6407 04:50:06,613 --> 04:50:09,049 SAY, OKAY, LET'S JUST GET THE 6408 04:50:09,049 --> 04:50:09,817 ANTI-INFLAMMATORY EFFECT WITH 6409 04:50:09,817 --> 04:50:11,018 THESE PARAMETERS AND LET'S JUST 6410 04:50:11,018 --> 04:50:13,053 GET THIS EFFECT ON DIABETES OR, 6411 04:50:13,053 --> 04:50:14,621 YOU KNOW, THAT'S THE GOAL, 6412 04:50:14,621 --> 04:50:15,055 RIGHT? 6413 04:50:15,055 --> 04:50:16,156 THAT'S A LONG WAY AWAY. 6414 04:50:16,156 --> 04:50:17,891 BUT THAT'S THE IDEA THROUGH THAT 6415 04:50:17,891 --> 04:50:22,062 APPROACH. 6416 04:50:22,062 --> 04:50:23,730 YEAH. 6417 04:50:23,730 --> 04:50:24,798 >> ALL RIGHT. 6418 04:50:24,798 --> 04:50:27,968 I COULD LISTEN TO THIS FOR HOURS 6419 04:50:27,968 --> 04:50:29,937 AND ASK QUESTIONS, BUT IT'S TIME 6420 04:50:29,937 --> 04:50:32,005 TO CLOSE. 6421 04:50:32,005 --> 04:50:35,609 SO I WANTED TO GIVE THANKS TO 6422 04:50:35,609 --> 04:50:42,449 OUR DISTINGUISHED PANEL. 6423 04:50:42,449 --> 04:50:52,159 AND I ALSO WANTED TO INVITE 6424 04:50:52,159 --> 04:51:02,536 DR. WEN CHEN TO CLOSE. 6425 04:51:03,504 --> 04:51:06,240 >> WELL, I NORMALLY DON'T DO THE 6426 04:51:06,240 --> 04:51:08,742 CLOSING REMARK, I ASK FOR IC 6427 04:51:08,742 --> 04:51:11,478 DIRECTOR TO DO IT, BUT THEY 6428 04:51:11,478 --> 04:51:11,745 DECLINED. 6429 04:51:11,745 --> 04:51:16,850 SO THEY ASKED I DO THIS PUMPING 6430 04:51:16,850 --> 04:51:17,017 UP. 6431 04:51:17,017 --> 04:51:18,952 I ASKED, WOULD YOU LIKE TO DO 6432 04:51:18,952 --> 04:51:22,222 IT, WALTER? 6433 04:51:22,222 --> 04:51:23,724 SO I DON'T KNOW WHY, THEY SAID 6434 04:51:23,724 --> 04:51:26,827 YOU NEED TO GIVE AN ENTHUSIASTIC 6435 04:51:26,827 --> 04:51:27,060 CLOSING. 6436 04:51:27,060 --> 04:51:29,963 SO I DON'T KNOW, I WAS TRYING TO 6437 04:51:29,963 --> 04:51:32,199 GET TO A LITTLE BIT MORE 6438 04:51:32,199 --> 04:51:33,600 INTEROCEPTION JUST NOW BECAUSE I 6439 04:51:33,600 --> 04:51:35,369 GOT OVERLOADED BY THE 6440 04:51:35,369 --> 04:51:36,770 EXTRASENSORY INPUT TODAY. 6441 04:51:36,770 --> 04:51:39,606 AND THEN I INSTANTLY FELT MY 6442 04:51:39,606 --> 04:51:41,141 RACING HEARTBEAT, SO I WAS LIKE, 6443 04:51:41,141 --> 04:51:43,243 OKAY, THAT'S NOT GOOD. 6444 04:51:43,243 --> 04:51:45,445 BUT ANYWAY, I JUST WANT TO THANK 6445 04:51:45,445 --> 04:51:48,315 ALL OF YOU FOR COMING TODAY AND 6446 04:51:48,315 --> 04:51:50,751 FOR THE ONLINE VIEWERS. 6447 04:51:50,751 --> 04:51:51,985 I KNOW THERE ARE HUNDREDS OF YOU 6448 04:51:51,985 --> 04:51:53,520 THERE, AND YOU CAN WATCH THIS 6449 04:51:53,520 --> 04:51:55,589 VIDEO LATER ON IF YOU MISSED 6450 04:51:55,589 --> 04:51:56,456 SOME EARLIER OF THE DAY. 6451 04:51:56,456 --> 04:52:01,995 AND I ALSO WANT TO THANK ARDEM 6452 04:52:01,995 --> 04:52:03,297 PATAPOUTIAN WHO HAS BEEN GETTING 6453 04:52:03,297 --> 04:52:05,799 UP AT 6:00 OR MAYBE EVEN 6454 04:52:05,799 --> 04:52:07,134 EARLIER, TO STAY WITH US THE 6455 04:52:07,134 --> 04:52:08,635 WHOLE DAY, HE TOLD ME HE WAS 6456 04:52:08,635 --> 04:52:09,603 THERE FROM THE VERY BEGINNING 6457 04:52:09,603 --> 04:52:11,171 AND I KNOW THAT'S A VERY EARLY 6458 04:52:11,171 --> 04:52:11,471 TIME. 6459 04:52:11,471 --> 04:52:16,209 AND ALSO, I WANTED TO SORT OF 6460 04:52:16,209 --> 04:52:17,844 SHARE, I KNOW I HURRIED 6461 04:52:17,844 --> 04:52:19,479 MANUFACTURE YOU OUT OF YOUR 6462 04:52:19,479 --> 04:52:22,215 POSTER BEFORE THE SESSION, I 6463 04:52:22,215 --> 04:52:23,951 PROMISED, YOU CAN GET BACK AT 6464 04:52:23,951 --> 04:52:25,485 FOUR, I KNOW WE'RE A LITTLE BIT 6465 04:52:25,485 --> 04:52:27,254 LATE, BUT THIS IS NETWORKING 6466 04:52:27,254 --> 04:52:28,355 TIME, WE RESERVED THIS TIME FOR 6467 04:52:28,355 --> 04:52:29,856 YOU TO CONTINUE YOUR WONDERFUL 6468 04:52:29,856 --> 04:52:31,858 DISCUSSIONS, YOU CAN GO BACK TO 6469 04:52:31,858 --> 04:52:33,160 THE POSTER SESSION, YOU CAN STAY 6470 04:52:33,160 --> 04:52:34,561 THERE UNTIL 5:30. 6471 04:52:34,561 --> 04:52:35,996 YOU DO HAVE TO TAKE THEM ALL 6472 04:52:35,996 --> 04:52:37,864 DOWN BY 5:30. 6473 04:52:37,864 --> 04:52:40,701 AND ALSO, TO CONTINUE. 6474 04:52:40,701 --> 04:52:42,336 SO THAT'S WHERE IT IS. 6475 04:52:42,336 --> 04:52:45,606 AND ALSO, I WANTED TO MAYBE 6476 04:52:45,606 --> 04:52:47,608 LET'S SEE IF THIS IS THE -- I 6477 04:52:47,608 --> 04:52:49,443 WANTED TO REMIND YOU ALL, IF YOU 6478 04:52:49,443 --> 04:52:51,979 LIKE THE EXCITEMENT TODAY, I 6479 04:52:51,979 --> 04:52:53,380 PROMISE IT WILL BE CONTINUED FOR 6480 04:52:53,380 --> 04:52:59,119 THREE DAYS IN A ROW IN 2025, I 6481 04:52:59,119 --> 04:53:00,420 GUESS, THE SEASON. 6482 04:53:00,420 --> 04:53:03,256 OH, YEAH, THAT SLIDE WAS NOT 6483 04:53:03,256 --> 04:53:03,490 UPDATED. 6484 04:53:03,490 --> 04:53:06,560 BUT IT'S IN THE SPRING OF 2025. 6485 04:53:06,560 --> 04:53:08,562 AND PLEASE LOOK OUT FOR IT, AND 6486 04:53:08,562 --> 04:53:11,465 WE HAVE A WONDERFUL DPAISH IS WE 6487 04:53:11,465 --> 04:53:13,200 HAVE WONDERFUL ORGANIZERS LISTED 6488 04:53:13,200 --> 04:53:13,567 HERE. 6489 04:53:13,567 --> 04:53:15,502 AND THANK YOU ALL FOR BEING WITH 6490 04:53:15,502 --> 04:53:17,504 US TODAY. 6491 04:53:17,504 --> 04:53:19,773 AND PLEASE STAY IN TOUCH WITH 6492 04:53:19,773 --> 04:53:19,940 US. 6493 04:53:19,940 --> 04:53:21,642 WE WANT TO BE HERE AND HELP AND 6494 04:53:21,642 --> 04:53:22,609 SUPPORT ALL OF YOU. 6495 04:53:22,609 --> 04:53:32,609 THANK YOU.