1 00:00:05,320 --> 00:00:09,400 WELCOME EVERYONE TO THIS NIA 2 00:00:09,400 --> 00:00:11,160 VIRTUAL WORKSHOP TITLED 3 00:00:11,160 --> 00:00:12,360 HARNESSING COMPUTATIONAL 4 00:00:12,360 --> 00:00:14,240 APPROACHES TO ADVANCING AIMING 5 00:00:14,240 --> 00:00:15,200 AND ALZHEIMER'S DISEASE AND 6 00:00:15,200 --> 00:00:16,760 ALZHEIMER'S DISEASE RELATED 7 00:00:16,760 --> 00:00:17,600 DEMENTIA RESEARCH. 8 00:00:17,600 --> 00:00:19,440 MY NAME IS MATT SUTTER A PROGRAM 9 00:00:19,440 --> 00:00:21,040 DIRECTOR IN THE DIVISION OF 10 00:00:21,040 --> 00:00:22,280 NEURO SCIENCE WHICH ALONG WITH 11 00:00:22,280 --> 00:00:24,360 THE DIVISION OF AGING BIOLOGY 12 00:00:24,360 --> 00:00:26,480 AND BEHAVIORAL AND SOCIAL 13 00:00:26,480 --> 00:00:28,120 RESEARCH ARE CO-SPONSORING THIS 14 00:00:28,120 --> 00:00:28,800 WORKSHOP. 15 00:00:28,800 --> 00:00:30,400 FOR THOSE WHO MAY NOT HAVE 16 00:00:30,400 --> 00:00:34,120 PARTICIPATED OR VIEWED AN NIA 17 00:00:34,120 --> 00:00:36,520 WORKSHOP BEFORE, THESE WORKSHOPS 18 00:00:36,520 --> 00:00:38,880 ARE USED BY NIA PROGRAM STAFF 19 00:00:38,880 --> 00:00:40,120 AND INSTITUTE LEADERSHIP TO 20 00:00:40,120 --> 00:00:41,800 BETTER UNDERSTAND THE STATE OF 21 00:00:41,800 --> 00:00:43,120 THE ART SCIENCE AND PARTICULAR 22 00:00:43,120 --> 00:00:44,400 TOPIC AREAS AND HEAR FROM 23 00:00:44,400 --> 00:00:46,880 LEADING RESEARCHERS, AND 24 00:00:46,880 --> 00:00:48,200 IMPORTANTLY UNDERSTANDING THE 25 00:00:48,200 --> 00:00:50,800 GAPS IN THE CURRENT LANDSCAPE 26 00:00:50,800 --> 00:00:51,640 AND OPPORTUNITIES FOR 27 00:00:51,640 --> 00:00:52,080 DEVELOPMENT. 28 00:00:52,080 --> 00:00:54,240 AS SUCH, THE AGENDA HAS TIME FOR 29 00:00:54,240 --> 00:00:56,000 DISCUSSION BETWEEN OUR WORKSHOP 30 00:00:56,000 --> 00:00:57,200 PARTICIPANTS TO BEST PROBE THE 31 00:00:57,200 --> 00:00:59,080 URGE ENTER QUESTIONS AND UNMET 32 00:00:59,080 --> 00:01:00,080 OPPORTUNITIES FOR THE FIELD. 33 00:01:00,080 --> 00:01:01,680 THE GOAL OF THIS WORKSHOP IS IS 34 00:01:01,680 --> 00:01:03,080 TO EXPLORE COMPUTATIONAL 35 00:01:03,080 --> 00:01:04,480 APPROACHES TO ADVANCING OUR 36 00:01:04,480 --> 00:01:06,920 STUDY OF AGING AND AD/ADRD. 37 00:01:06,920 --> 00:01:08,240 THERE'S BEEN A RAPID DEVELOPMENT 38 00:01:08,240 --> 00:01:10,280 OF FIELDS FROM COMPUTATIONAL 39 00:01:10,280 --> 00:01:11,840 BIOLOGY TO IMAGING AND MODELING 40 00:01:11,840 --> 00:01:14,080 AND SYSTEM AND BIO-INFORMATICS 41 00:01:14,080 --> 00:01:16,240 AND EXTENDED TO NEUROSCIENCE AS 42 00:01:16,240 --> 00:01:17,760 WELL WHERE COMPUTATIONAL SCIENCE 43 00:01:17,760 --> 00:01:20,680 IS AN INCOMPETENTER DISCIPLINARY 44 00:01:20,680 --> 00:01:22,760 FIELD FOR ANNAL DECISION OF 45 00:01:22,760 --> 00:01:24,200 MULTI SCALE MODEL AND NEURO 46 00:01:24,200 --> 00:01:26,480 FUNCTION AND MORE ADVANCES IN 47 00:01:26,480 --> 00:01:27,800 MACHINE LEARNING ARTIFICIAL 48 00:01:27,800 --> 00:01:29,200 INTELLIGENCE AND LARGE-SCALE 49 00:01:29,200 --> 00:01:30,640 DATASETS HAVE FACILITATED AN 50 00:01:30,640 --> 00:01:32,280 EXPLOSION OF RESEARCH ACROSS 51 00:01:32,280 --> 00:01:34,080 LEVELS OF BIOLOGY AND BEHAVIOR. 52 00:01:34,080 --> 00:01:35,960 AS REFLECTED, COMPUTATIONAL 53 00:01:35,960 --> 00:01:37,360 APPROACHES SPAN LEVELS OF 54 00:01:37,360 --> 00:01:38,400 ANALYSIS FROM MOLECULES THROUGH 55 00:01:38,400 --> 00:01:40,120 CELLS AND NETWORKS TO COGNITION 56 00:01:40,120 --> 00:01:41,080 AND BEHAVIOR. 57 00:01:41,080 --> 00:01:42,880 THIS WORKSHOP WILL EXPLORE 58 00:01:42,880 --> 00:01:44,520 CURRENT AND POTENTIAL 59 00:01:44,520 --> 00:01:45,680 APPLICATIONS OF COMPUTATIONAL 60 00:01:45,680 --> 00:01:47,240 APPROACHES TO THE STUDY OF AGING 61 00:01:47,240 --> 00:01:49,400 AND AD/ADRD TO HELP US BETTER 62 00:01:49,400 --> 00:01:51,360 UNDERSTAND KEY QUESTIONS. 63 00:01:51,360 --> 00:01:54,200 WITH THAT, I'D LIKE TO NOW 64 00:01:54,200 --> 00:01:56,000 INTRODUCE Dr. AMY KELLEY, WHO 65 00:01:56,000 --> 00:01:59,000 HAS SOME OPENING REMARKS TO 66 00:01:59,000 --> 00:01:59,480 SHARE. 67 00:01:59,480 --> 00:02:00,520 >>Amy Kelley: THANK YOU, MATT. 68 00:02:00,520 --> 00:02:03,040 AND WELCOME, EVERYONE. 69 00:02:03,040 --> 00:02:06,560 AND I'M HAPPY TO JOIN YOU FOR 70 00:02:06,560 --> 00:02:08,880 THIS EXCITING WORKSHOP VIRTUALLY 71 00:02:08,880 --> 00:02:12,080 AND AS YOU KNOW AND MATT STATED, 72 00:02:12,080 --> 00:02:14,520 THE GOAL IS TO EXPLORE THE 73 00:02:14,520 --> 00:02:15,600 COMPUTATIONAL APPROACHES TO 74 00:02:15,600 --> 00:02:17,040 ADVANCE THE STURDY OF AGING AND 75 00:02:17,040 --> 00:02:19,040 ALZHEIMER'S AND RELATED 76 00:02:19,040 --> 00:02:19,600 DEMENTIA. 77 00:02:19,600 --> 00:02:22,400 THIS WORK VERY COLLIERLY 78 00:02:22,400 --> 00:02:23,520 ALLIANCE WITH NIA'S MISSION TO 79 00:02:23,520 --> 00:02:24,920 UNDERSTAND THE NATURE AND AGING 80 00:02:24,920 --> 00:02:27,560 AND AGING PROCESS AND DISEASES 81 00:02:27,560 --> 00:02:28,880 AND CONDITIONS THAT ARE 82 00:02:28,880 --> 00:02:31,600 ASSOCIATED WITH GROWING OLDER, 83 00:02:31,600 --> 00:02:33,000 ALL IN ORDER TO EXTEND THE 84 00:02:33,000 --> 00:02:34,640 HEALTHY AND ACTIVE YEARS OF LIFE 85 00:02:34,640 --> 00:02:36,640 FOR OLDER ADULTS. 86 00:02:36,640 --> 00:02:38,560 THE FOCUS OF TODAY'S WORKSHOP 87 00:02:38,560 --> 00:02:42,000 CUTS ACROSS ALL OF OUR RESEARCH 88 00:02:42,000 --> 00:02:45,280 AREAS SO GENETICS, BIOLOGICAL, 89 00:02:45,280 --> 00:02:47,520 CLINICAL, BEHAVIORAL, SOCIAL AND 90 00:02:47,520 --> 00:02:50,520 ECONOMIC RESEARCH ON AGING. 91 00:02:50,520 --> 00:02:51,920 AND NIA IS COMMITTED TO 92 00:02:51,920 --> 00:02:55,560 ADVANCING THE MOST INNOVATIVE 93 00:02:55,560 --> 00:02:57,560 AREAS OF SCIENCE BY INVESTING IN 94 00:02:57,560 --> 00:02:58,600 PROJECTS AND INFRASTRUCTURE THAT 95 00:02:58,600 --> 00:03:00,720 APPLY CUTTING EDGE APPROACHES TO 96 00:03:00,720 --> 00:03:02,040 FILL CRITICAL GAPS AND RESEARCH 97 00:03:02,040 --> 00:03:05,920 AND COVER REAND FACILITATING THE 98 00:03:05,920 --> 00:03:07,200 BROAD RESEARCH DATA AND THE 99 00:03:07,200 --> 00:03:08,760 RESOURCE THAT'S ARE DEVELOPED 100 00:03:08,760 --> 00:03:10,200 WITH PUBLIC FUNDS, WHICH IS 101 00:03:10,200 --> 00:03:12,200 CENTRAL TO OUR COMMITMENT. 102 00:03:12,200 --> 00:03:14,040 IN THAT SPIRIT, I WANTED TO 103 00:03:14,040 --> 00:03:17,480 SHARE WITH YOU JUST A COUPLE OF 104 00:03:17,480 --> 00:03:18,760 EXAMPLES OF NIA-FUNDED PROGRAMS 105 00:03:18,760 --> 00:03:20,200 IN THIS REALM. 106 00:03:20,200 --> 00:03:22,160 THE FIRST IS PROJECT CALLED 107 00:03:22,160 --> 00:03:24,040 TARGET ENABLEMENT TO ACCELERATE 108 00:03:24,040 --> 00:03:25,160 THERAPY DEVELOPMENT FOR 109 00:03:25,160 --> 00:03:26,880 ALZHEIMER'S DISEASE. 110 00:03:26,880 --> 00:03:28,920 OR TREAT AD. 111 00:03:28,920 --> 00:03:30,000 THIS DEVELOPS HIGH-QUALITY 112 00:03:30,000 --> 00:03:31,560 RESEARCH TOOLS AND TECHNOLOGY 113 00:03:31,560 --> 00:03:35,640 THAT IS NEEDED TO VALIDATE AND 114 00:03:35,640 --> 00:03:37,600 ADVANCE THE NEXT GENERATION OF 115 00:03:37,600 --> 00:03:40,120 DRUG TARGETS FOR ALZHEIMER'S. 116 00:03:40,120 --> 00:03:41,760 THE DATA, THE RESEARCH 117 00:03:41,760 --> 00:03:43,080 METHODOLOGIES AND THE 118 00:03:43,080 --> 00:03:45,040 COMPUTATIONAL AND EXPERIMENTAL 119 00:03:45,040 --> 00:03:46,880 TOOLS ARE DISSEMINATED OPENLY 120 00:03:46,880 --> 00:03:48,440 AND FREE OF CHARGE TO THE 121 00:03:48,440 --> 00:03:49,680 BROADER RESEARCH COMMUNITY FOR 122 00:03:49,680 --> 00:03:52,080 NOT USE AND DRUG DISCOVERY AND 123 00:03:52,080 --> 00:03:53,360 RESEARCH THAT WILL HELP BETTER 124 00:03:53,360 --> 00:03:55,480 UNDERSTAND THE COMPLEX BIOLOGY 125 00:03:55,480 --> 00:03:57,120 OF THE DISEASE. 126 00:03:57,120 --> 00:03:59,560 ANOTHER EXAMPLE IS THE NEW NIA 127 00:03:59,560 --> 00:04:02,480 ARTIFICIAL INTELLIGENCE AND 128 00:04:02,480 --> 00:04:04,480 TECHNOLOGY COLLABORATORIES. 129 00:04:04,480 --> 00:04:04,960 AITC. 130 00:04:04,960 --> 00:04:06,960 THESE ARE DEDICATED TO HELPING 131 00:04:06,960 --> 00:04:10,120 AMERICANS LIVE LONGER, HEALTHIER 132 00:04:10,120 --> 00:04:11,880 LIVES THROUGH THE APPLICATION OF 133 00:04:11,880 --> 00:04:13,080 ARTIFICIAL INTELLIGENCE AND 134 00:04:13,080 --> 00:04:14,040 EMERGING TECHNOLOGIES. 135 00:04:14,040 --> 00:04:16,360 THE AITC WILL SERVE AS A 136 00:04:16,360 --> 00:04:17,880 NATIONAL RESERVE TO PROMOTE 137 00:04:17,880 --> 00:04:19,840 DEVELOPMENT AND IMPLEMENTATION 138 00:04:19,840 --> 00:04:22,920 OF AI APPROACHES ASK TECHNOLOGY 139 00:04:22,920 --> 00:04:24,440 THROUGH PIPPA CROSS INDUSTRY, 140 00:04:24,440 --> 00:04:26,240 HEALTHCARE SYSTEMS, AND VARIOUS 141 00:04:26,240 --> 00:04:30,400 OTHER STAKEHOLDERS UNDER THREE 142 00:04:30,400 --> 00:04:33,040 AITC COLLABORATORIES WHICH ARE 143 00:04:33,040 --> 00:04:34,120 CENTERED AT JOHNS HOPKINS 144 00:04:34,120 --> 00:04:36,480 UNIVERSITY OF MASSACHUSETTS 145 00:04:36,480 --> 00:04:38,280 AMHERST AND UNIVERSITY OF 146 00:04:38,280 --> 00:04:39,800 PENNSYLVANIA ALONG WITH A 147 00:04:39,800 --> 00:04:41,120 COORDINATING CENTER THAT IS 148 00:04:41,120 --> 00:04:43,120 MANAGED BY ROSALIE AND 149 00:04:43,120 --> 00:04:43,800 ASSOCIATES. 150 00:04:43,800 --> 00:04:45,640 THOSE ARE JUST TWO EXAMPLES OF 151 00:04:45,640 --> 00:04:50,240 WORK THAT NOT NI NIA IS SUPPORTS 152 00:04:50,240 --> 00:04:51,000 CASE. 153 00:04:51,000 --> 00:04:52,080 WE RECOGNIZE DATA SHARING. 154 00:04:52,080 --> 00:04:54,800 THIS IS A WAY TO ENSURE THE 155 00:04:54,800 --> 00:04:56,480 RIGOR, REPRODUCIBILITY AND 156 00:04:56,480 --> 00:04:59,200 TRANSPARENCY OF RESEARCH 157 00:04:59,200 --> 00:05:00,600 FINDINGS, SHARING SCIENTIFIC 158 00:05:00,600 --> 00:05:03,800 DATA ALSO CAN ACCELERATE 159 00:05:03,800 --> 00:05:06,160 BIOMEDICAL RESEARCH BY ENABLING 160 00:05:06,160 --> 00:05:07,720 VALIDATION OF RESEARCH ADULTS 161 00:05:07,720 --> 00:05:10,360 AND PROMOTING DATA REUSE FOR 162 00:05:10,360 --> 00:05:12,120 ADDITIONAL RESEARCH STUDIES. 163 00:05:12,120 --> 00:05:14,400 MANY OF YOU AND I'M CERTAIN ARE 164 00:05:14,400 --> 00:05:16,400 AWARE OF NIH'S NEW POLICY FOR 165 00:05:16,400 --> 00:05:18,320 DATA MANAGEMENT AND SHARING. 166 00:05:18,320 --> 00:05:20,080 IT CAME INTO EFFECT EARLIER THIS 167 00:05:20,080 --> 00:05:21,280 YEAR. 168 00:05:21,280 --> 00:05:23,400 IT REQUIRES ALL NIA FUNDED 169 00:05:23,400 --> 00:05:24,920 RESEARCHERS TO SUBMIT A PLAN 170 00:05:24,920 --> 00:05:26,680 PRIOR TO THEIR AWARD THAT 171 00:05:26,680 --> 00:05:29,880 OUTLINES HOW THEIR SCIENTIFIC 172 00:05:29,880 --> 00:05:31,560 DATA GENERATED BY THEIR RESEARCH 173 00:05:31,560 --> 00:05:33,080 WILL BE MANAGED AND SHARED. 174 00:05:33,080 --> 00:05:35,240 THE POLICY REALLY EMPHASISES 175 00:05:35,240 --> 00:05:37,040 GOOD DATA MANAGEMENT PRACTICES 176 00:05:37,040 --> 00:05:39,360 AND IT IS ESTABLISHING 177 00:05:39,360 --> 00:05:40,560 EXPECTATIONS FOR MAXIMIZING THE 178 00:05:40,560 --> 00:05:44,840 SHARING OF SCIENTIFIC DATA BEN 179 00:05:44,840 --> 00:05:46,520 RATED FROM PUBLICLY FUNDED 180 00:05:46,520 --> 00:05:46,960 RESEARCH. 181 00:05:46,960 --> 00:05:48,400 NIA IS WORKING ON GUIDANCE AND 182 00:05:48,400 --> 00:05:50,200 RESOURCE THAT'S WILL SUPPORT 183 00:05:50,200 --> 00:05:51,160 INVESTIGATORS SO THEY CAN SAFELY 184 00:05:51,160 --> 00:05:52,640 AND EFFICIENT LEHMAN AGE AND 185 00:05:52,640 --> 00:05:56,800 SHARE THE DATA FROM THEIR 186 00:05:56,800 --> 00:06:02,360 STUDIES. 187 00:06:02,360 --> 00:06:05,320 WE HAVE NIA RESOURCE FORCE DATA 188 00:06:05,320 --> 00:06:06,240 SPECIFIC TO ALZHEIMER'S AND THE 189 00:06:06,240 --> 00:06:07,960 BROADER AGING RESEARCH 190 00:06:07,960 --> 00:06:10,960 COMMUNITIES SO ONE OF THE 191 00:06:10,960 --> 00:06:13,360 EXAMPLES IS THE NIA DATA STORAGE 192 00:06:13,360 --> 00:06:15,520 THAT IS IS CO-OPERATIVE 193 00:06:15,520 --> 00:06:16,880 AGREEMENT THAT IS BETWEEN NIA 194 00:06:16,880 --> 00:06:18,640 AND THE UNIVERSITY OF 195 00:06:18,640 --> 00:06:20,280 PENNSYLVANIA. 196 00:06:20,280 --> 00:06:21,640 ALSO THE NIA KNOWLEDGE PORTAL, 197 00:06:21,640 --> 00:06:26,040 WHICH IS CREATED THROUGH THE 198 00:06:26,040 --> 00:06:26,720 ACCELERATED MEDICINE PIP AND 199 00:06:26,720 --> 00:06:29,840 AGING RESEARCH BIOBANK AND ALL 200 00:06:29,840 --> 00:06:32,480 OF THESE AND THE NEW DATA 201 00:06:32,480 --> 00:06:34,960 SHARING POLICY IN GENERAL WE 202 00:06:34,960 --> 00:06:37,480 EXPECT TO OPEN A WIDE RANGE OF 203 00:06:37,480 --> 00:06:38,920 NEW OPPORTUNITIES FOR 204 00:06:38,920 --> 00:06:40,320 RESEARCHERS TO CONDUCT 205 00:06:40,320 --> 00:06:41,520 COMPUTATIONAL RESEARCH WITH 206 00:06:41,520 --> 00:06:45,160 THESE EXISTING DATA SOURCES. 207 00:06:45,160 --> 00:06:47,400 SO, AS MENTIONED, TODAY'S 208 00:06:47,400 --> 00:06:49,760 WORKSHOP IS A COLLABORATIVE 209 00:06:49,760 --> 00:06:50,000 EFFORT. 210 00:06:50,000 --> 00:06:51,640 IT WAS ORGANIZED BY STAFF FROM 211 00:06:51,640 --> 00:06:53,760 NIA DIVISION OF NEUROSCIENCE, 212 00:06:53,760 --> 00:06:55,320 THE DIVISION OF BEHAVIORAL AND 213 00:06:55,320 --> 00:06:58,040 SOCIAL RESEARCH AND AGING 214 00:06:58,040 --> 00:06:59,960 BIOLOGY. 215 00:06:59,960 --> 00:07:02,080 YOU ALL ARE SPEAKERS AND 216 00:07:02,080 --> 00:07:02,840 PARTICIPANTS, AND BRING TOGETHER 217 00:07:02,840 --> 00:07:05,760 A WIDE RANGE OF EXPERTISE AND 218 00:07:05,760 --> 00:07:06,840 PERSPECTIVES TO DISCUSS THE 219 00:07:06,840 --> 00:07:08,360 POWER OF COMPUTATIONAL 220 00:07:08,360 --> 00:07:10,360 APPROACHES TO ANALYZING 221 00:07:10,360 --> 00:07:12,600 MOLECULAR SYSTEMS, LARGE-SCALE 222 00:07:12,600 --> 00:07:15,120 BRAIN SYSTEMS, NOT COMPLEX 223 00:07:15,120 --> 00:07:17,280 BEHAVIORAL PATTERNS AND MANY 224 00:07:17,280 --> 00:07:19,040 OTHER TOPICS. 225 00:07:19,040 --> 00:07:21,120 IT'S ALSO, WE'RE HOPING AN 226 00:07:21,120 --> 00:07:22,040 IMPORTANT OPPORTUNITY TO HEAR 227 00:07:22,040 --> 00:07:26,840 FROM THE COMMUNITY ABOUT THE 228 00:07:26,840 --> 00:07:31,160 RESIZE AND STRENGTHEN AND 229 00:07:31,160 --> 00:07:35,440 ACCELERATE AND WE HOPE OVER THE 230 00:07:35,440 --> 00:07:38,080 NEXT TWO DAYS WE HOPE WE CAN 231 00:07:38,080 --> 00:07:39,160 EXPLORE THIS SPACE TOGETHER AND 232 00:07:39,160 --> 00:07:41,400 THESE DISCUSSIONS SPARK NEW 233 00:07:41,400 --> 00:07:42,440 COLLABORATIONS BETWEEN 234 00:07:42,440 --> 00:07:43,880 COMPUTATIONAL AND DATA 235 00:07:43,880 --> 00:07:46,000 SCIENTISTS AND RESEARCHERS 236 00:07:46,000 --> 00:07:48,400 ACROSS AGING RESEARCH 237 00:07:48,400 --> 00:07:50,680 DISCIPLINES THAT WILL ADDRESS A 238 00:07:50,680 --> 00:07:52,160 RANGE OF IMPORTANT RESEARCH 239 00:07:52,160 --> 00:07:54,160 QUESTIONS RELATE TODAY AGING AND 240 00:07:54,160 --> 00:07:59,480 NEURO DEGENERATION. 241 00:07:59,480 --> 00:08:01,200 THANK YOU FOR JOINING US AND 242 00:08:01,200 --> 00:08:02,400 CONTRIBUTING TO THIS IMPORTANT 243 00:08:02,400 --> 00:08:03,840 DISCUSSION AND ALONG WITH YOU, 244 00:08:03,840 --> 00:08:05,480 I'LL LOOK FORWARD TO HEARING THE 245 00:08:05,480 --> 00:08:08,440 SPEAKERS AND DISCUSSIONS TODAY 246 00:08:08,440 --> 00:08:10,200 AND LEARNING HOW WE CAN BETTER 247 00:08:10,200 --> 00:08:12,520 HARNESS COMPUTATIONAL APPROACHES 248 00:08:12,520 --> 00:08:13,880 OF AGING AND ALZHEIMER'S AND 249 00:08:13,880 --> 00:08:16,600 RELATED DEMENTIAS. 250 00:08:16,600 --> 00:08:18,400 MATT THANK YOU SO MUCH, Dr. 251 00:08:18,400 --> 00:08:18,880 KELLY. 252 00:08:18,880 --> 00:08:20,720 I JUST WANTED TO SHARE A FEW 253 00:08:20,720 --> 00:08:22,160 ADDITIONAL LOGISTICAL DETAILS 254 00:08:22,160 --> 00:08:23,480 BEFORE WE GET STARTED. 255 00:08:23,480 --> 00:08:25,360 I WILL REMIND SPEAKERS TO PLEASE 256 00:08:25,360 --> 00:08:27,880 KEEP THEIR LINES MUTED UNLESS 257 00:08:27,880 --> 00:08:28,200 SPEAKING. 258 00:08:28,200 --> 00:08:30,720 IN ADDITION, PLEASE TURN YOUR 259 00:08:30,720 --> 00:08:33,040 VIDEO ON DURING THE DISCUSSIONS 260 00:08:33,040 --> 00:08:34,400 DISCUSSION AND AT THE END OF THE 261 00:08:34,400 --> 00:08:34,800 WORKSHOP. 262 00:08:34,800 --> 00:08:36,080 DURING THE TALKS, PLEASE KEEP 263 00:08:36,080 --> 00:08:38,200 YOUR VIDEO OFF UP LESS YOUR 264 00:08:38,200 --> 00:08:39,240 PRESENTING. 265 00:08:39,240 --> 00:08:42,520 THIS IS JUST FOR THE BROADCAST 266 00:08:42,520 --> 00:08:44,240 FEED. 267 00:08:44,240 --> 00:08:45,440 PLEASE USE -- IF YOU HAVE A 268 00:08:45,440 --> 00:08:46,760 QUESTION OR COMMENT DURING THE 269 00:08:46,760 --> 00:08:47,880 DISCUSSIONS, PLEASE USE THE 270 00:08:47,880 --> 00:08:49,480 RAISE HAND FEATURE IN ZOOM SO WE 271 00:08:49,480 --> 00:08:51,040 KNOW TO CALL ON YOU OR DROP A 272 00:08:51,040 --> 00:08:52,360 QUESTION IN THE CHAT AND DON'T 273 00:08:52,360 --> 00:08:57,640 FORGET TO LOWER YOUR HAPP HAND U 274 00:08:57,640 --> 00:08:58,560 ASKED YOUR QUESTIONS. 275 00:08:58,560 --> 00:08:59,400 SPEAKERS WILL HAVE 20 MINUTES 276 00:08:59,400 --> 00:09:01,560 FOR THE HOCKEY AND WE'LL HOLD 277 00:09:01,560 --> 00:09:02,280 QUESTIONS FOR DISCUSSION SESSION 278 00:09:02,280 --> 00:09:05,760 AT THE END OF EACH SESSION. 279 00:09:05,760 --> 00:09:07,840 NIA STAFF WILL PROVIDE TIME 280 00:09:07,840 --> 00:09:09,320 REMAINDER AND AT THE END OF THE 281 00:09:09,320 --> 00:09:15,080 20 MINUTES AND WE WILL CUT YOU 282 00:09:15,080 --> 00:09:16,240 OFF AND. 283 00:09:16,240 --> 00:09:20,120 FOR EVERYONE VIEWING THIS 284 00:09:20,120 --> 00:09:21,400 MEETING AND APPROXIMATE THE LIVE 285 00:09:21,400 --> 00:09:22,800 FEEDBACK FORM AND WE WILL TRY TO 286 00:09:22,800 --> 00:09:24,600 BRING THESE QUESTIONS UP DURING 287 00:09:24,600 --> 00:09:25,720 THE DISCUSSION QUESTION. 288 00:09:25,720 --> 00:09:27,120 DURING THE DISCUSSION SESSIONS, 289 00:09:27,120 --> 00:09:28,520 OR IF THE QUESTION IS MORE 290 00:09:28,520 --> 00:09:29,960 SPECIFIC TO A PARTICULAR 291 00:09:29,960 --> 00:09:31,440 SPEAKER, WE MAY FORWARD THAT 292 00:09:31,440 --> 00:09:32,760 QUESTION TO THE INDIVIDUAL FOR 293 00:09:32,760 --> 00:09:35,040 FOLLOW-UP AFTER THE MEETING. 294 00:09:35,040 --> 00:09:35,880 PLEASE UNDERSTAND WE MAY NOT 295 00:09:35,880 --> 00:09:39,720 HAVE TIME TO GET TO EVERY 296 00:09:39,720 --> 00:09:40,040 QUESTION. 297 00:09:40,040 --> 00:09:41,600 FOR THOSE OF YOU WHO ARE 298 00:09:41,600 --> 00:09:42,920 REGISTERED OR MAY BE UNABLE TO 299 00:09:42,920 --> 00:09:44,920 VIEW THE WORKSHOP LIVE, WE WILL 300 00:09:44,920 --> 00:09:46,440 RECORD THE WORKSHOP AND NOTIFY 301 00:09:46,440 --> 00:09:48,960 YOU THROUGH THE EVENT BRIGHT 302 00:09:48,960 --> 00:09:50,000 REGISTRATION WHEN THE RECORDINGS 303 00:09:50,000 --> 00:09:52,840 ARE AVAILABLE. 304 00:09:52,840 --> 00:09:54,760 ONE LAST NOTE, I WOULD LIKE TO 305 00:09:54,760 --> 00:09:56,600 RECOGNIZE THE OTHER NIA PROGRAM 306 00:09:56,600 --> 00:09:57,360 STAFF WHO WORKED WITH ME OVER 307 00:09:57,360 --> 00:09:59,040 THE LAST FEW MONTHS AND HAVE 308 00:09:59,040 --> 00:10:03,000 BEEN IPSOS-REID M INSTRUMENTAL S 309 00:10:03,000 --> 00:10:03,280 TOGETHER. 310 00:10:03,280 --> 00:10:06,120 MY COLLEAGUES Dr. AMANDA 311 00:10:06,120 --> 00:10:08,720 DEBAUTISTA AND CAREER SAINT 312 00:10:08,720 --> 00:10:13,520 CLARK AND Dr.LY NODE AND 313 00:10:13,520 --> 00:10:14,760 BEHAVIORAL AND SOCIAL RESERVE 314 00:10:14,760 --> 00:10:16,280 LUKE STOKAL, JEANNINE SIMMONS 315 00:10:16,280 --> 00:10:22,800 AND ELIZABETH . 316 00:10:22,800 --> 00:10:25,160 Dr. DAVE FRANKOUSKI WHO SPENT 317 00:10:25,160 --> 00:10:27,280 A LOT OF TIME AND EFFORT 318 00:10:27,280 --> 00:10:31,240 MANAGING THE DETAILS FOR THE 319 00:10:31,240 --> 00:10:34,360 WORKSHOP AND WILL HELP RUN 320 00:10:34,360 --> 00:10:35,440 THINGS THE NEXT TWO DAYS. 321 00:10:35,440 --> 00:10:37,200 WITH THAT, WE'LL TRANSITION INTO 322 00:10:37,200 --> 00:10:39,240 OUR FIRST SESSION A BIT EARLY. 323 00:10:39,240 --> 00:10:49,760 I WILL PASS THINGS OVER TO THE 324 00:10:50,200 --> 00:10:50,520 DEAN GLADYSHEV. 325 00:10:50,520 --> 00:10:51,600 >>THANK YOU, MATT. 326 00:10:51,600 --> 00:10:54,120 WELCOME EVERYBODY TO THE FIRST 327 00:10:54,120 --> 00:10:54,520 SESSION. 328 00:10:54,520 --> 00:10:56,720 OUR EXCITING FIRST SESSION IS 329 00:10:56,720 --> 00:10:58,160 COMPUTATIONAL ANALYSIS OF 330 00:10:58,160 --> 00:10:59,680 MOLECULAR SYSTEMS. 331 00:10:59,680 --> 00:11:05,800 MY NAME IS VADIM GLADYSHEV. 332 00:11:05,800 --> 00:11:08,040 I'M AT HARVARD MEDICAL SCHOOL 333 00:11:08,040 --> 00:11:12,680 AND OUR SECOND SPEAKER WILL BE 334 00:11:12,680 --> 00:11:14,520 NAN HOA FROM UNIVERSITY OF 335 00:11:14,520 --> 00:11:15,160 CALIFORNIA SAN DIEGO AND HE WILL 336 00:11:15,160 --> 00:11:17,360 TELL US ABOUT ENGINEERING 337 00:11:17,360 --> 00:11:20,400 LONGEVITY OF SINGLE CELL AGING 338 00:11:20,400 --> 00:11:23,360 AFTER A BREAK WE'LL HAVE PAOLA 339 00:11:23,360 --> 00:11:25,480 SEBASTIANI FROM TUFTS MEDICAL 340 00:11:25,480 --> 00:11:28,440 CENTER TELLING US ABOUT 341 00:11:28,440 --> 00:11:32,440 COMPUTATIONAL WORKING THIS -- IF 342 00:11:32,440 --> 00:11:37,200 I UNDERSTAND CORRECTLY AND OUR 343 00:11:37,200 --> 00:11:40,280 FINAL SPEAKER ALREADY ALEXEY 344 00:11:40,280 --> 00:11:41,800 TERSKIKH AND HE WILL TELLS US 345 00:11:41,800 --> 00:11:47,960 ABOUT MICROSCOPING IMAGING OF 346 00:11:47,960 --> 00:11:54,600 HETEROGENEITY. 347 00:11:54,600 --> 00:11:55,880 SO I ENCOURAGE YOU TO PLACE 348 00:11:55,880 --> 00:12:01,120 QUESTIONS IN THE CHAT SO WE WILL 349 00:12:01,120 --> 00:12:05,240 KEEP THE QUESTIONS FOR THE 350 00:12:05,240 --> 00:12:06,680 DISCUSSION SESSION. 351 00:12:06,680 --> 00:12:09,360 SO, I'M THE FIRST SPEAKER AND I 352 00:12:09,360 --> 00:12:11,280 THINK WE'LL JUST SHARE MY OF 353 00:12:11,280 --> 00:12:14,920 SCREEN AND BEGIN THE 354 00:12:14,920 --> 00:12:25,160 PRESENTATION. 355 00:12:29,720 --> 00:12:31,640 >>SO HE WILL TILL YOU ABOUT 356 00:12:31,640 --> 00:12:37,160 AGING TODAY AND FIRST, JUST, HOW 357 00:12:37,160 --> 00:12:38,720 WE APPROACH THIS QUESTION OF 358 00:12:38,720 --> 00:12:45,320 QUANTWANTING AGING. 359 00:12:45,320 --> 00:12:45,520 WANT 360 00:12:45,520 --> 00:12:54,280 FYIQUAQUESTION OFQUANTIFYING AGE 361 00:12:54,280 --> 00:12:56,080 SCALE SPINNING MANY SPECIES OF 362 00:12:56,080 --> 00:12:57,720 MAMMALS AND TRYING TO UNDERSTAND 363 00:12:57,720 --> 00:12:59,960 HOW NATURE CHANGES LIFESPAN AS 364 00:12:59,960 --> 00:13:02,600 WELL AS ACROSS THIS STUDY IN 365 00:13:02,600 --> 00:13:05,840 MICE WHERE THE ANALYZE WHAT 366 00:13:05,840 --> 00:13:07,560 DIFFERENT INTERVENTIONS THAT 367 00:13:07,560 --> 00:13:09,440 EXTEND LIFESPAN IF THEY ARE 368 00:13:09,440 --> 00:13:11,960 COMMON IN ONE AND WHAT ARE THE 369 00:13:11,960 --> 00:13:16,600 ACTUAL BASIC PRINCIPL PRINCIPLEE 370 00:13:16,600 --> 00:13:16,880 LIFESPAN. 371 00:13:16,880 --> 00:13:21,280 THIS IS LONGEVITY AND HAVE THE 372 00:13:21,280 --> 00:13:22,560 POTENTIAL OF THE SYSTEM TO LIVE 373 00:13:22,560 --> 00:13:25,000 LONG AND THIS SIGNATURE CAN BE 374 00:13:25,000 --> 00:13:27,960 USED TO IDENTIFY A NEW 375 00:13:27,960 --> 00:13:30,560 INTERVENTIONS BOTH IN 376 00:13:30,560 --> 00:13:32,440 INTERCEPTIONS AND THAT MIGHT 377 00:13:32,440 --> 00:13:35,160 INDUCE LONGEVITY IN CELLS, 378 00:13:35,160 --> 00:13:37,160 TISSUES AND ORGANS. 379 00:13:37,160 --> 00:13:40,320 AT THE SAME TIME, WE ALSO WORK 380 00:13:40,320 --> 00:13:45,120 WITH AGING AND SO OF COURSE THE 381 00:13:45,120 --> 00:13:46,160 POTENTIAL TO LIVE LONG AND AGING 382 00:13:46,160 --> 00:13:47,920 PROGRESSION THROUGH A LIFE 383 00:13:47,920 --> 00:13:51,800 COURSE IS KIND OF OUR -- SO 384 00:13:51,800 --> 00:13:57,080 HERE, WE DEVELOP BIOMARKERS 385 00:13:57,080 --> 00:13:58,240 CLOCKS, GENETIC CLOCKS THAN 386 00:13:58,240 --> 00:14:00,960 QUANTIFY AGING, AND ALSO CAUSAL 387 00:14:00,960 --> 00:14:03,360 BIOMARKERS WHICH RESULTS IN 388 00:14:03,360 --> 00:14:05,960 ACTIONABLE BIOMARKERS OF AGING. 389 00:14:05,960 --> 00:14:09,440 WE USE THEM A LOT AND ALSO A 390 00:14:09,440 --> 00:14:13,040 THIRD COMPONENT IS RENEW NATION 391 00:14:13,040 --> 00:14:14,640 OF SIGNATURES WHEN WE INDUCE THE 392 00:14:14,640 --> 00:14:16,440 TRADITIONAL SYSTEM FROM THE 393 00:14:16,440 --> 00:14:19,040 OLDEST STATE TO THE YOUNGEST 394 00:14:19,040 --> 00:14:19,360 STATE. 395 00:14:19,360 --> 00:14:22,560 THIS ALLOWS US TO TARGET AGE 396 00:14:22,560 --> 00:14:24,400 INTERVENTIONS AND TEST VARIOUS 397 00:14:24,400 --> 00:14:27,600 APPROACHES HERE BOTH GENETIC, 398 00:14:27,600 --> 00:14:29,360 FARM CO LOGICAL AND NUTRITIONAL 399 00:14:29,360 --> 00:14:30,800 AND TODAY BECAUSE IT'S SHORT, I 400 00:14:30,800 --> 00:14:33,160 WILL MOSTLY FOCUS ON WANT FYING 401 00:14:33,160 --> 00:14:43,720 AGING ON THIS PART OF THE SLIDE. 402 00:14:49,560 --> 00:14:51,280 WE'LL START IN A WAY. 403 00:14:51,280 --> 00:14:54,600 ABOUT 10 YEARS AGO AND AS FAR AS 404 00:14:54,600 --> 00:14:56,040 I KNOW, STEVE HORVATH WAS THE 405 00:14:56,040 --> 00:14:59,200 FIRST ONE TO BASICALLY DESCRIBE 406 00:14:59,200 --> 00:15:01,120 A EPIGENETIC BIOMARKER AND THIS 407 00:15:01,120 --> 00:15:03,120 IS HIS FAMOUS PAPER IN 2013 AND 408 00:15:03,120 --> 00:15:06,600 SINCE THEN, THERE HAVE BEEN MANY 409 00:15:06,600 --> 00:15:10,960 CLOCKS PUBLISHED LIKE GRIM AGE, 410 00:15:10,960 --> 00:15:12,840 PINOT AGE, AND MANY, MANY OTHER 411 00:15:12,840 --> 00:15:13,080 CLOCKS. 412 00:15:13,080 --> 00:15:14,400 OF COURSE NOW IT'S JUST 413 00:15:14,400 --> 00:15:16,320 IMPOSSIBLE TO FOLLOW ALL THE 414 00:15:16,320 --> 00:15:18,200 LITERATURE OF TENS OF THOUSANDS 415 00:15:18,200 --> 00:15:18,880 OF PAPERS. 416 00:15:18,880 --> 00:15:21,040 IT'S A REVOLUTION. 417 00:15:21,040 --> 00:15:25,840 HE CON HAVE YOU CONTRIBUTED ON E 418 00:15:25,840 --> 00:15:26,160 SIDE. 419 00:15:26,160 --> 00:15:28,160 BUT OF COURSE, OTHER LABS ALSO 420 00:15:28,160 --> 00:15:29,600 DEVELOPED QUITE A FEW CLOCKS IN 421 00:15:29,600 --> 00:15:32,080 BLUE HERE, ARE PAPERS FROM OUR 422 00:15:32,080 --> 00:15:33,640 LAB AND THERE ARE OTHER PAPERS 423 00:15:33,640 --> 00:15:40,080 FROM OTHER LABS. 424 00:15:40,080 --> 00:15:40,960 THERE ARE OTHER CLOCKS AS WELL 425 00:15:40,960 --> 00:15:45,080 BUT THE MICROBIOME AND THERE ARE 426 00:15:45,080 --> 00:15:45,960 MANY CLOCKS CURRENT AND 427 00:15:45,960 --> 00:15:46,200 AVAILABLE. 428 00:15:46,200 --> 00:15:47,680 THIS IS JUST AN ILLUSTRATION OF 429 00:15:47,680 --> 00:15:50,400 HOW IT WORKS. 430 00:15:50,400 --> 00:15:52,000 THIS WAS OUR FIRST CLOCK WE 431 00:15:52,000 --> 00:15:54,880 DESCRIBED IN THE MOUSE WHERE WE 432 00:15:54,880 --> 00:15:59,480 SEQUENCES ABOUT 200 MICE BY 433 00:15:59,480 --> 00:16:02,880 METHODS CALLED -- FROM VERY 434 00:16:02,880 --> 00:16:05,920 YOUNG TO 35 MONTHS OLD MOUSE. 435 00:16:05,920 --> 00:16:10,760 AND BY APPLYING MACHINE 436 00:16:10,760 --> 00:16:13,560 LEARNING, FROM MINIMUM YUN OF 437 00:16:13,560 --> 00:16:16,440 SCIENCE BY SEQUENCING THE 438 00:16:16,440 --> 00:16:19,880 IDENTIFY MICE WHICH PRESENTED A 439 00:16:19,880 --> 00:16:22,240 MATHEMATICAL MODEL WITH 440 00:16:22,240 --> 00:16:23,800 BIOLOGICAL AGE TO THE MOUSE SO 441 00:16:23,800 --> 00:16:25,840 FOR EXAMPLE, HERE, YOU CAN SEE 442 00:16:25,840 --> 00:16:28,000 THE ACTUAL AGE AND PREDICTIVE 443 00:16:28,000 --> 00:16:30,640 AGE AND THERE'S A GOOD 444 00:16:30,640 --> 00:16:32,240 CORRESPONDENCE IN HERE AND IN 445 00:16:32,240 --> 00:16:33,320 THIS IN RED THERE ARE FOUR 446 00:16:33,320 --> 00:16:35,960 GROUPS OF MICE WHICH WERE 447 00:16:35,960 --> 00:16:36,680 SUBJECTED TO CALORIE RESTRICTION 448 00:16:36,680 --> 00:16:38,840 AND WE CAN SEE BASED ON THIS 449 00:16:38,840 --> 00:16:40,720 CLOCK WE CAN SEE THESE MICE ARE 450 00:16:40,720 --> 00:16:43,520 YOUNGER, BIOLOGICALLY YOUNGER 451 00:16:43,520 --> 00:16:45,520 AND OF COURSE THEY ALSO LIVE 452 00:16:45,520 --> 00:16:45,760 LONGER. 453 00:16:45,760 --> 00:16:49,560 AND THIS IS NOT AN EXAMPLE WHERE 454 00:16:49,560 --> 00:16:52,240 AGE MATCHED MICE COMPARED BUT IN 455 00:16:52,240 --> 00:16:54,720 THE GROUND AND ALSO GROWTH FROM 456 00:16:54,720 --> 00:16:57,040 YOU CAN SEE THAT THE KNOCK OUT 457 00:16:57,040 --> 00:16:58,480 MOUSE WAS YOUNGER AND THIS 458 00:16:58,480 --> 00:17:00,240 MOUSE LIVES 40% LONGER. 459 00:17:00,240 --> 00:17:03,800 AND FINALLY, WHEN WE APPLY THIS 460 00:17:03,800 --> 00:17:06,800 CLOCK TO OTHER SYSTEMS, FOR 461 00:17:06,800 --> 00:17:09,680 EXAMPLE, IN HERE, WE COLLECTED 462 00:17:09,680 --> 00:17:12,760 FIBER BLASTS FROM THE KIDNEY AND 463 00:17:12,760 --> 00:17:14,160 FROM LUNG AND WE PROGRAMMED THEM 464 00:17:14,160 --> 00:17:15,520 INTO INDUCE THE IMPORTANT STEM 465 00:17:15,520 --> 00:17:19,760 CELLS AND YOU CAN SEE THAT THE 466 00:17:19,760 --> 00:17:22,440 AGE DROPPED TO ZERO AND IT IT 467 00:17:22,440 --> 00:17:25,560 MEANS THAT AGING CLOCK, EVEN 468 00:17:25,560 --> 00:17:27,000 THOUGH IT WAS DEVELOPED FOR THE 469 00:17:27,000 --> 00:17:28,560 ADULT AGES IT TICKS DURING THE 470 00:17:28,560 --> 00:17:30,920 DEVELOPMENT AS WELL AND IT'S 471 00:17:30,920 --> 00:17:33,760 CORRECTLY PREDICTING THE AGE OF 472 00:17:33,760 --> 00:17:36,240 ZERO FOR THESE EMBRYONIC LIFE 473 00:17:36,240 --> 00:17:39,480 CELLS. 474 00:17:39,480 --> 00:17:41,640 SO, THIS OF COURSE THERE ARE 475 00:17:41,640 --> 00:17:44,640 MANY CLOCKS LIKE THIS BASED ON 476 00:17:44,640 --> 00:17:45,440 CLOCK. 477 00:17:45,440 --> 00:17:47,360 BUT NOT, WE RECENTLY DEVELOPED 478 00:17:47,360 --> 00:17:51,280 ANOTHER TYPE OF CLOCK WHICH IS 479 00:17:51,280 --> 00:17:55,760 IS A FLEXIBLE SCALABLE FRAMEWORK 480 00:17:55,760 --> 00:17:59,320 FOR PREDICTION AT A SINGLE CELL 481 00:17:59,320 --> 00:18:01,840 EVOLUTION. 482 00:18:01,840 --> 00:18:04,080 DEVELOPED BY ALEX TRAPP A 483 00:18:04,080 --> 00:18:07,840 TALENTED MEMBER OF OUR LAB. 484 00:18:07,840 --> 00:18:09,640 THE WAY IT WORKS, IT ACTUALLY 485 00:18:09,640 --> 00:18:11,280 WORKS AT SINGLE CELL LEVEL. 486 00:18:11,280 --> 00:18:14,880 HERE WE APPLY THIS TO THE SCH 487 00:18:14,880 --> 00:18:18,480 FOR SINGLE CELL AGE AND TO CELLS 488 00:18:18,480 --> 00:18:19,360 IN THE MOUSE. 489 00:18:19,360 --> 00:18:20,520 SO FOR EXAMPLE, THIS IS A MOUSE 490 00:18:20,520 --> 00:18:24,520 WHICH IS THREE TO SIX MONTHS OLD 491 00:18:24,520 --> 00:18:25,840 AND THIS INDIVIDUAL THIS IS THE 492 00:18:25,840 --> 00:18:27,120 ACTUAL AGE OF THE MOUSE AND YOU 493 00:18:27,120 --> 00:18:30,840 CAN SEE THAT THERE'S A QUITE 494 00:18:30,840 --> 00:18:32,760 NICELY PREDICT THE AGE OF 495 00:18:32,760 --> 00:18:34,560 INDIVIDUAL CELLS AND THIS IS A 496 00:18:34,560 --> 00:18:36,120 YOUNGER MOUSE, FOUR-MONTH-OLD 497 00:18:36,120 --> 00:18:42,760 MOUSE, THIS IS FOUR MONTHS MARK 498 00:18:42,760 --> 00:18:47,480 AND THIS IS ALSO THE QUANTIFY 499 00:18:47,480 --> 00:18:50,680 AND BIOLOGICAL AGE AND FROM THIS 500 00:18:50,680 --> 00:18:59,000 IT APPEARS AND EVEN THOUGH MANY 501 00:18:59,000 --> 00:19:00,960 PROGRESS THROUGH AGING AND SOME 502 00:19:00,960 --> 00:19:03,440 CELLS WHICH SEEM TO AGE FASTER 503 00:19:03,440 --> 00:19:08,160 HERE WE FIND SOME CELLS AND SOME 504 00:19:08,160 --> 00:19:10,280 CELLS THEY SHOW INCREASED 505 00:19:10,280 --> 00:19:12,120 BIOLOGICAL AGE COMPARED TO OTHER 506 00:19:12,120 --> 00:19:14,160 CELLS AND ON THE OTHER HAND WE 507 00:19:14,160 --> 00:19:15,800 FOUND THAT SOME CELLS, 508 00:19:15,800 --> 00:19:19,680 PARTICULARLY STEM CELLS, THEY 509 00:19:19,680 --> 00:19:21,160 AGE SLOWER. 510 00:19:21,160 --> 00:19:22,240 MUSCLE STEM CELLS. 511 00:19:22,240 --> 00:19:24,480 THEY ACTUALLY SHOW REDUCED 512 00:19:24,480 --> 00:19:25,800 BIOLOGICAL AGE COMPARED TO OTHER 513 00:19:25,800 --> 00:19:36,040 CELLS IN THE TISSUE. 514 00:19:36,040 --> 00:19:37,680 THERE'S THE BIOLOGICAL AGE. 515 00:19:37,680 --> 00:19:42,440 IT CREATES COMPLEXITY AND IT'S 516 00:19:42,440 --> 00:19:43,640 GOING TO NEW THINKING ABOUT THE 517 00:19:43,640 --> 00:19:45,960 TISSUE AGING AND CELL AGING AND 518 00:19:45,960 --> 00:19:50,200 IT REQUIRES DEVELOPMENT OF NEW 519 00:19:50,200 --> 00:19:53,240 METHODS. 520 00:19:53,240 --> 00:19:56,760 ANOTHER EXAMPLE HERE IS THE 521 00:19:56,760 --> 00:19:59,280 PLACE WHERE HE HAVE UNDER REVIEW 522 00:19:59,280 --> 00:20:01,040 WHERE WE FOUND SEVERE STRESS 523 00:20:01,040 --> 00:20:02,200 INCREASES BIOLOGICAL AGE AND 524 00:20:02,200 --> 00:20:04,840 WHEN THE STRESS IS RELIEVED, THE 525 00:20:04,840 --> 00:20:07,160 AGE IS DECREASED. 526 00:20:07,160 --> 00:20:09,440 WE THINK IN TERMS OF THAT 527 00:20:09,440 --> 00:20:11,200 BIOLOGICAL AGE IS NOT STARTED, 528 00:20:11,200 --> 00:20:14,040 IT'S NOT CHRONOLOGICAL AGE THAT 529 00:20:14,040 --> 00:20:16,600 GROWS THIS AGE BUT INSTEAD IT'S 530 00:20:16,600 --> 00:20:18,520 FLUCTUATES SOME DEPENDING ON THE 531 00:20:18,520 --> 00:20:19,560 CONDITION. 532 00:20:19,560 --> 00:20:21,480 AND THE FULL STRESS OF SEVERE 533 00:20:21,480 --> 00:20:23,040 STRESS WE DESCRIBED IN THIS 534 00:20:23,040 --> 00:20:26,760 STUDY IS IS A MAJOR SURGERY LIKE 535 00:20:26,760 --> 00:20:30,640 FOR EXAMPLE HIP FRACTURE, IS 536 00:20:30,640 --> 00:20:34,040 OFTEN A EMERGENCY SURGERY OR 537 00:20:34,040 --> 00:20:36,400 COVID INFECTION HERE IS NOT JUST 538 00:20:36,400 --> 00:20:37,480 INFECTION BUT WHEN SOMEONE GOES 539 00:20:37,480 --> 00:20:39,720 TO THE HOSPITAL TO THE ICU TO 540 00:20:39,720 --> 00:20:41,120 THE VENTILATOR AND AT THAT POINT 541 00:20:41,120 --> 00:20:43,480 YOU SEE THE BIOLOGICAL AGE IS 542 00:20:43,480 --> 00:20:45,840 INCREASED AND WHEN THE RETURN 543 00:20:45,840 --> 00:20:47,920 RECOVERS IT'S DECREASED. 544 00:20:47,920 --> 00:20:51,800 PREGNANCY THEY SAW THE INCREASED 545 00:20:51,800 --> 00:20:54,480 AGE IN THIRD TRIMESTER AND 546 00:20:54,480 --> 00:20:56,240 DECREASES POSTPARTUM. 547 00:20:56,240 --> 00:20:58,920 WE CONNECT YOUNG AND OLD MICE 548 00:20:58,920 --> 00:21:01,280 AND THEY OBSERVED THAT THE YOUNG 549 00:21:01,280 --> 00:21:03,880 MOUSE ACTUALLY THE BIOLOGICAL 550 00:21:03,880 --> 00:21:07,560 AGE IS INCREASED VERY 551 00:21:07,560 --> 00:21:08,760 SIGNIFICANTLY WHEN THIS MICE 552 00:21:08,760 --> 00:21:10,080 ESTABLISH COMMON CIRCULATION BUT 553 00:21:10,080 --> 00:21:11,720 WHEN WE SEPARATE THE MICE, THEN 554 00:21:11,720 --> 00:21:13,960 THE BIOLOGICAL AGE ALSO 555 00:21:13,960 --> 00:21:14,920 RECOVERS. 556 00:21:14,920 --> 00:21:17,320 SO, WE DON'T CALL IT 557 00:21:17,320 --> 00:21:18,040 REJUVENATION IN THIS PARTICULAR 558 00:21:18,040 --> 00:21:19,240 CASE BECAUSE WE DON'T KNOW. 559 00:21:19,240 --> 00:21:21,600 WE JUST SAY IT'S A BIOLOGICAL 560 00:21:21,600 --> 00:21:25,040 AGE IS NOT STATIC, IT'S 561 00:21:25,040 --> 00:21:26,120 FLUCTUATES AND SEVERE STRESS 562 00:21:26,120 --> 00:21:28,600 MIGHT INCREASE IT. 563 00:21:28,600 --> 00:21:32,880 BUT ACTUALLY, SPEAKING OF 564 00:21:32,880 --> 00:21:33,920 REJUVENATION, WE HAVE A STUDY 565 00:21:33,920 --> 00:21:35,680 WHERE WE WANT TO APPLY OUR 566 00:21:35,680 --> 00:21:37,080 CLOCKS TO SEE WHETHER THE AGE 567 00:21:37,080 --> 00:21:38,680 COULD BE ACTUALLY REVERSED 568 00:21:38,680 --> 00:21:42,600 WHETHER ORGANISMS CAN BE 569 00:21:42,600 --> 00:21:43,520 REJUVENATED AND WE CONNECT A 570 00:21:43,520 --> 00:21:45,720 YOUNG MOUSE AND AN OLD MOUSE SO 571 00:21:45,720 --> 00:21:46,960 THAT THEY ESTABLISH COMMON 572 00:21:46,960 --> 00:21:50,400 CIRCULATION AND THIS IS WORK IN 573 00:21:50,400 --> 00:21:52,280 COLLABORATION WITH JEAN WHITE AT 574 00:21:52,280 --> 00:21:52,680 DURING UNIVERSITY. 575 00:21:52,680 --> 00:21:54,320 AFTER THREE MONTHS, WE SEPARATE 576 00:21:54,320 --> 00:21:57,040 THEM AND FOLLOW WHAT HAPPENS 577 00:21:57,040 --> 00:21:58,080 WITH THIS MICE. 578 00:21:58,080 --> 00:21:59,880 AND APPLY THE CLOCKS. 579 00:21:59,880 --> 00:22:02,040 FIRST WE FIND THAT ACTUALLY THE 580 00:22:02,040 --> 00:22:04,920 MICE, THE OLD MICE, AFTER THEY 581 00:22:04,920 --> 00:22:08,280 ESTABLISHED A COMMON CIRCULATION 582 00:22:08,280 --> 00:22:09,720 WITH THE YOUNG MOUSE THEY LIVE 583 00:22:09,720 --> 00:22:10,080 LONGER. 584 00:22:10,080 --> 00:22:12,560 AND ALSO, WHEN WE APPLY THE 585 00:22:12,560 --> 00:22:14,840 CLOCKS, THEN WE ALSO FIND THAT 586 00:22:14,840 --> 00:22:22,600 THEY ARE TRULY REJUVENATED AND 587 00:22:22,600 --> 00:22:23,960 THIS IS IN THE LIVER, IN THE 588 00:22:23,960 --> 00:22:25,120 BLOOD AND THIS IS JUST ONE 589 00:22:25,120 --> 00:22:26,640 EXAMPLE OF THE CLOCK THAT I SHOW 590 00:22:26,640 --> 00:22:28,800 HERE BASED ON THE REDUCE 591 00:22:28,800 --> 00:22:30,440 REPRESENTATION OF SEQUENCING BUT 592 00:22:30,440 --> 00:22:33,040 WE ALSO APPLIED RA BASED CLOCKS 593 00:22:33,040 --> 00:22:35,280 IN COLLABORATION WITH STEVE 594 00:22:35,280 --> 00:22:37,560 HORVATH AND IT SHOWS ALL THE 595 00:22:37,560 --> 00:22:37,880 SAME. 596 00:22:37,880 --> 00:22:39,800 IT'S VERY, VERY DRAMATIC AND 597 00:22:39,800 --> 00:22:42,840 VERY STRONG EFFECT OF 598 00:22:42,840 --> 00:22:43,920 REJUVENATION. 599 00:22:43,920 --> 00:22:47,720 SO, NOW I WANT TO BRING ISSUE. 600 00:22:47,720 --> 00:22:49,520 IT'S ALL GOOD AT THE AGING CAN 601 00:22:49,520 --> 00:22:50,200 BE QUANTIFIED. 602 00:22:50,200 --> 00:22:52,080 HOWEVER, THERE ARE MANY 603 00:22:52,080 --> 00:22:52,480 CHALLENGES. 604 00:22:52,480 --> 00:22:53,880 I WILL DISCUSS EVEN MORE ABOUT 605 00:22:53,880 --> 00:22:55,400 THESE CHALLENGES BUT FOR NOW, 606 00:22:55,400 --> 00:22:57,160 LET ME BRING THIS CHALLENGE. 607 00:22:57,160 --> 00:23:07,720 I SO USE MY AND TO GO WE COMPARE 608 00:23:09,400 --> 00:23:11,000 A YOUNG MAN AND A OLD MAN AND 609 00:23:11,000 --> 00:23:13,600 WHAT DO WE OBSERVE HIS AGE. 610 00:23:13,600 --> 00:23:14,400 WE OBSERVE THAT FOR EXAMPLE THE 611 00:23:14,400 --> 00:23:15,880 HAIR BECOMES GRAY AND ALSO 612 00:23:15,880 --> 00:23:18,560 THERE'S A HAIR LOSS. 613 00:23:18,560 --> 00:23:20,160 BUT THIS CHANGES KIND OF NOT 614 00:23:20,160 --> 00:23:20,720 CAUSAL. 615 00:23:20,720 --> 00:23:22,120 SO THEY JUST HAPPEN AND THEY 616 00:23:22,120 --> 00:23:23,840 DON'T REALLY INFLUENCE AGE PER 617 00:23:23,840 --> 00:23:24,320 SE. 618 00:23:24,320 --> 00:23:27,360 BUT THEN WE ALSO OBSERVE, FOR 619 00:23:27,360 --> 00:23:29,480 EXAMPLE, INCREASED USE OF 620 00:23:29,480 --> 00:23:31,960 GLASSES OR ALSO HEARING AID OR 621 00:23:31,960 --> 00:23:36,360 MAYBE SOME OTHER SITUATIONS IN A 622 00:23:36,360 --> 00:23:38,800 WHEELCHAIR OR WE COULD QUANTIFY 623 00:23:38,800 --> 00:23:40,600 LIKE NUMBERS OF VISITS TO DOCTOR 624 00:23:40,600 --> 00:23:41,760 OFFICES AND ALL THE PEOPLE MORE 625 00:23:41,760 --> 00:23:43,840 OFTEN GO DOCTOR OFFICE AND WE 626 00:23:43,840 --> 00:23:45,680 COULD USE THIS FEATURES TO 627 00:23:45,680 --> 00:23:46,920 DEVELOP A CLOCK. 628 00:23:46,920 --> 00:23:48,520 WE WOULD PREDICT THE AGE 629 00:23:48,520 --> 00:23:51,040 BASICALLY ON THE FEATURES LIKE 630 00:23:51,040 --> 00:23:52,760 GLASSES, HEARING AID, VISITS TO 631 00:23:52,760 --> 00:23:54,560 DOCTOR USING A WHEELCHAIR AND SO 632 00:23:54,560 --> 00:23:57,160 ON BUT THEN, IF YOU LET'S SAY 633 00:23:57,160 --> 00:24:00,280 FIRE ALL DOCTORS, BASED ON THIS 634 00:24:00,280 --> 00:24:01,080 CLOCK, EVERYBODY WILL BE YOUNG 635 00:24:01,080 --> 00:24:04,320 BECAUSE NO ONE GOES TO DOCTORS, 636 00:24:04,320 --> 00:24:04,960 THERE'S NO ONE USES GLASSES BUT 637 00:24:04,960 --> 00:24:08,360 OF COURSE IT'S NOT TRUE. 638 00:24:08,360 --> 00:24:18,800 SO THIS IS BECAUSE WE WHEN 639 00:24:23,120 --> 00:24:24,320 DEVELOP THE CLOCKS THESE 640 00:24:24,320 --> 00:24:26,000 FEATURES, THEY HAVE THE AGING 641 00:24:26,000 --> 00:24:28,080 PROCESS AND THEY DO NOT -- THEY 642 00:24:28,080 --> 00:24:30,520 ARE NOT AGING PER SE SO, IT'S 643 00:24:30,520 --> 00:24:36,360 IMPORTANT FOR US TO SEPARATE AGE 644 00:24:36,360 --> 00:24:38,520 CHANGES INTO PER SE AND NEUTRAL 645 00:24:38,520 --> 00:24:40,520 CHANGES IN ADOPTIVE CHANGES AND 646 00:24:40,520 --> 00:24:42,600 THIS IS JUST ANOTHER EXAMPLE 647 00:24:42,600 --> 00:24:45,800 THAT WORK IN PROGRESS. 648 00:24:45,800 --> 00:24:48,160 A STUDENT IN THE LAB, HE APPLIED 649 00:24:48,160 --> 00:24:52,640 OF METHODS OF COMBINED WITH 650 00:24:52,640 --> 00:25:00,320 CHANGES TO IDENTIFY OF CPG SIZE 651 00:25:00,320 --> 00:25:02,200 IN DELENATIONS CAUSAL TO AGING. 652 00:25:02,200 --> 00:25:04,920 WE ARE DIVIDE A SUBSET WHICH ARE 653 00:25:04,920 --> 00:25:07,040 MORE CAUSAL MEANING THAT THEY 654 00:25:07,040 --> 00:25:10,120 ACTUALLY WORKED TOWARDS USING 655 00:25:10,120 --> 00:25:10,440 LESS. 656 00:25:10,440 --> 00:25:15,000 BUT ALSO, IDENTIFIED PROTECTIVE 657 00:25:15,000 --> 00:25:17,000 SIDES ADAPTIVE SIDES THAT 658 00:25:17,000 --> 00:25:18,520 INCREASE THE LIFESPAN AND THEN 659 00:25:18,520 --> 00:25:20,920 USING THESE SITES, THEY MADE 660 00:25:20,920 --> 00:25:22,000 SEPARATE CLOCKS AND WE CALLED 661 00:25:22,000 --> 00:25:23,640 THEM AGE FOR DAMAGING. 662 00:25:23,640 --> 00:25:26,720 AND THE OTHER ONE ADOPT AGE 663 00:25:26,720 --> 00:25:27,520 FORAY CAPTIVE CHANGES AND BOTH 664 00:25:27,520 --> 00:25:29,080 OF THEM WORK WELL. 665 00:25:29,080 --> 00:25:33,720 THEY CAN PREDICT THE AGE BASED 666 00:25:33,720 --> 00:25:42,880 ON THESE CLOCKS. 667 00:25:42,880 --> 00:25:45,000 YOU CAN SEE THEM AGE, 668 00:25:45,000 --> 00:25:47,600 DAMAGE-BASED CLOCK SHOWS 669 00:25:47,600 --> 00:25:49,000 REJUVENATION WHERE ADOPTED AGE 670 00:25:49,000 --> 00:25:51,160 DOES NOT. 671 00:25:51,160 --> 00:25:52,880 SO, AGAIN, IT'S A CHALLENGE IN 672 00:25:52,880 --> 00:25:55,680 THE FIELD OF HOW WE QUANTIFY AND 673 00:25:55,680 --> 00:25:57,880 WHEN WE CAN APPLY THESE CLOCKS 674 00:25:57,880 --> 00:25:59,080 IN THE DIRECTION FROM YOUNG TO 675 00:25:59,080 --> 00:26:04,480 OLD BUT ALSO FROM OLD TO YOUNG. 676 00:26:04,480 --> 00:26:06,000 ANOTHER EXAMPLE WE FOUND 677 00:26:06,000 --> 00:26:07,760 RECENTLY AND THIS IS ANOTHER 678 00:26:07,760 --> 00:26:13,560 EXAMPLE OF REJUVENATION, WE 679 00:26:13,560 --> 00:26:16,160 FOUND THAT AT THE LEVEL OF COP 680 00:26:16,160 --> 00:26:22,840 EXCEPTION, THAT THE ZYGOTE IS 681 00:26:22,840 --> 00:26:24,000 ZERO AND IT'S STABLE AND THEN 682 00:26:24,000 --> 00:26:29,400 IT'S REDUCED TO THE LEVEL OF THE 683 00:26:29,400 --> 00:26:31,120 STAGE THEY CALL IS IS GROUND 684 00:26:31,120 --> 00:26:33,040 ZERO WHEN IT'S PREDICTED 685 00:26:33,040 --> 00:26:34,320 BIOLOGICAL AGE IT'S THE LOWEST 686 00:26:34,320 --> 00:26:36,640 AND THEN AGING BEGINS HERE AND 687 00:26:36,640 --> 00:26:38,680 OF COURSE DEVELOP PRESSES AND 688 00:26:38,680 --> 00:26:40,560 ALSO WE OBSERVED IN INCREASED 689 00:26:40,560 --> 00:26:42,480 BIOLOGICAL AGE AND WE'VE DONE IT 690 00:26:42,480 --> 00:26:44,240 IN MICE, WE'VE DONE IT WILL IN 691 00:26:44,240 --> 00:26:46,760 HUMANS AND QUANTIFY THE SINGLE 692 00:26:46,760 --> 00:26:52,720 CELL LEVEL AND WE ALSO HAVE MANY 693 00:26:52,720 --> 00:26:54,400 SCRIPT IN (INAUDIBLE). 694 00:26:54,400 --> 00:26:56,400 AND THEN IF YOU APPLY OUR SINGLE 695 00:26:56,400 --> 00:26:59,080 CELL CLOCK IN THIS CASE, WE FIND 696 00:26:59,080 --> 00:27:01,880 THAT DURING MOUSE DEVELOPMENT 697 00:27:01,880 --> 00:27:04,040 FROM 4.5 TO 7.5 DAYS AND THIS 698 00:27:04,040 --> 00:27:10,520 LEVEL OF 80 PLUS WE OBSERVE 699 00:27:10,520 --> 00:27:11,760 REJUVENATION YOU CAN SEE THEY 700 00:27:11,760 --> 00:27:16,640 SHOW REDUCED AGE FROM 4.5 TO 7.5 701 00:27:16,640 --> 00:27:17,520 DAYS. 702 00:27:17,520 --> 00:27:19,440 IF WE LOOK AT THE INDIVIDUAL 703 00:27:19,440 --> 00:27:24,520 CELL TYPES FOR EXAMPLE, THEY ALL 704 00:27:24,520 --> 00:27:27,720 ARE RENEW NATUR JUVE NATURED. 705 00:27:27,720 --> 00:27:29,400 IT SHOWS FOR EXAMPLE IT'S A 706 00:27:29,400 --> 00:27:39,920 PLACENTA LATER AND AND THIS TAKE 707 00:27:41,760 --> 00:27:44,520 BIOMARKER HELPS US IN THEM. 708 00:27:44,520 --> 00:27:50,040 AND WE RECENTLY -- WHEN YOU IT'S 709 00:27:50,040 --> 00:27:52,320 VERY HARD WHEN YOU TRY IT. 710 00:27:52,320 --> 00:27:55,360 IT'S LESS STABLE THAN SO IT'S 711 00:27:55,360 --> 00:27:56,520 MORE DIFFICULT N THIS CASE THIS 712 00:27:56,520 --> 00:27:58,760 CLOCK IS BASED MORE THAN 3,000 713 00:27:58,760 --> 00:28:00,800 SAMPLES AND MANY OF THEM FROM 714 00:28:00,800 --> 00:28:02,440 DATABASES AND A HUGE META 715 00:28:02,440 --> 00:28:04,360 ANALYSIS AND ALSO WE HAVE FOR 716 00:28:04,360 --> 00:28:07,600 MANY OF THE THESE SAMPLES THE 717 00:28:07,600 --> 00:28:11,920 SEQUENCE PARTICULARLY ESSENTIAL 718 00:28:11,920 --> 00:28:12,720 INTERVENTIONS THROUGH THE 719 00:28:12,720 --> 00:28:15,760 PROGRAM SUPPORT BY NIA AND SO IF 720 00:28:15,760 --> 00:28:17,880 YOU COULD ADJUST FOR LIFESPAN. 721 00:28:17,880 --> 00:28:20,960 THERE'S A GOOD CORRESPONDENCE 722 00:28:20,960 --> 00:28:22,480 WITHIN THE PREDICT AND ACTUAL 723 00:28:22,480 --> 00:28:23,040 AGE OF THE MICE. 724 00:28:23,040 --> 00:28:25,920 WHEN YOU APPLY THE AGE TO 725 00:28:25,920 --> 00:28:29,560 DATASET YOU SEE REJUVENATION OF 726 00:28:29,560 --> 00:28:30,760 EMBRYONIC DEVELOPMENT. 727 00:28:30,760 --> 00:28:34,120 NOW, I'D LIKE TO BRING THE 728 00:28:34,120 --> 00:28:44,480 ISSUES HERE SO WE HAVE 729 00:29:00,920 --> 00:29:02,640 MEASUREMENTS FOR FRAIL SEE, CELL 730 00:29:02,640 --> 00:29:03,600 COMPOSITION, SYSTEMIC CHANGES 731 00:29:03,600 --> 00:29:05,560 AND HOW DO WE TRAIN THE CLOCKS 732 00:29:05,560 --> 00:29:11,520 AND DO WE TRAIN THEM FOR LOSS OF 733 00:29:11,520 --> 00:29:12,600 FUNCTION, FORAY APPEARANCE OF 734 00:29:12,600 --> 00:29:15,920 DISEASES FOR MORTALITY THESE ARE 735 00:29:15,920 --> 00:29:19,680 ALL MANIFESTATION OF THE AGING 736 00:29:19,680 --> 00:29:20,880 PROCESS AND WHILE THEY'RE 737 00:29:20,880 --> 00:29:21,920 RELATED TO ONE ANOTHER THEY'RE 738 00:29:21,920 --> 00:29:22,880 NOT THE SAME. 739 00:29:22,880 --> 00:29:23,920 WHEN THEY BUILT THE CLOCKS, THEY 740 00:29:23,920 --> 00:29:25,200 BUILT THEM IN DIFFERENT WAYS AND 741 00:29:25,200 --> 00:29:26,960 THERE'S CURRENTLY NO HOW EXACTLY 742 00:29:26,960 --> 00:29:28,760 THEY SHOULD DO IT AND SECOND, 743 00:29:28,760 --> 00:29:30,760 HOW DO WE RELATE AGING AT THE 744 00:29:30,760 --> 00:29:33,320 LEVEL OF SINGLE CELL, TISSUE OR 745 00:29:33,320 --> 00:29:34,240 THE CELL OF THE ORGANS. 746 00:29:34,240 --> 00:29:36,480 THIS IS AN UNI INVOLVED 747 00:29:36,480 --> 00:29:36,760 QUESTION. 748 00:29:36,760 --> 00:29:39,560 ANOTHER ONE IS AGING ADAPTATION. 749 00:29:39,560 --> 00:29:43,120 I SHOWED YOU A SLIDE. 750 00:29:43,120 --> 00:29:49,360 ADAPT TAV AND DAMAGING CHANGES 751 00:29:49,360 --> 00:29:51,920 AND THE DEVELOPMENT PROCESS IS 752 00:29:51,920 --> 00:29:56,160 ALSO END UP IN THE CLOCKS AND 753 00:29:56,160 --> 00:30:00,720 DEVELOPMENT FEATURES AND IT'S 754 00:30:00,720 --> 00:30:05,520 THE SIMULATOR AND IT'S A MAIN 755 00:30:05,520 --> 00:30:12,360 PROCESS IN THE ORDER AND HOW 756 00:30:12,360 --> 00:30:22,880 THEY AND MID MANY AIR THEY'RE 757 00:30:25,120 --> 00:30:27,280 DIFFERENT AND IT'S DEVELOPMENTAL 758 00:30:27,280 --> 00:30:32,000 GENES AND IN THE PRO MOTORS AND 759 00:30:32,000 --> 00:30:40,120 ENHANCER AND THE CHANGES FROM 760 00:30:40,120 --> 00:30:42,680 YOUNG TO OLD ARE NOT THE SAME AS 761 00:30:42,680 --> 00:30:45,080 THE TRANSITION FROM THE OLD TO 762 00:30:45,080 --> 00:30:46,720 THE YOUNG STATE AND SO WHETHER 763 00:30:46,720 --> 00:30:48,400 THE CLOCKS TO BE APPLIED IN ONE 764 00:30:48,400 --> 00:30:50,200 CASE MAYBE NOT THE ACTUALLY 765 00:30:50,200 --> 00:30:51,600 APPLICABLE IN THE OTHER CASE. 766 00:30:51,600 --> 00:30:54,600 AND FINALLY, IT'S VERY EXPENSE 767 00:30:54,600 --> 00:31:05,000 IDF TO ANALYZE SO BEGIN 768 00:31:12,360 --> 00:31:15,760 ADDRESSING THAT, PERFORM A 769 00:31:15,760 --> 00:31:17,360 CONSORTIUM IN FACT WE ANNOUNCED 770 00:31:17,360 --> 00:31:19,880 IT JUST YESTERDAY. 771 00:31:19,880 --> 00:31:20,920 THIS INVOLVES ABOUT 25 LESS HERE 772 00:31:20,920 --> 00:31:23,960 AND MANY SENIOR PEOPLE, LEADERS 773 00:31:23,960 --> 00:31:27,760 IN THE FIELD, MANY OF THEM WHO 774 00:31:27,760 --> 00:31:29,040 DEVELOPED BIOMARKERS AND MANY 775 00:31:29,040 --> 00:31:31,160 USE BIOMARKERS. 776 00:31:31,160 --> 00:31:36,920 HERE, LUIGI, STEVE HORVATH, AND 777 00:31:36,920 --> 00:31:39,080 MANY OTHERS THIS IS A COMMUNITY 778 00:31:39,080 --> 00:31:45,120 EXECUTIVE COMMITTEE AND ALSO 779 00:31:45,120 --> 00:31:47,200 HERE WE USE THE CLOCK BASE AND 780 00:31:47,200 --> 00:31:49,000 THIS IS ON-LINE AND FORM TO HELP 781 00:31:49,000 --> 00:31:52,040 EXPLORE AND ANALYZE BIOLOGICAL 782 00:31:52,040 --> 00:31:55,920 AGE ACROSS GEODATABASE SO IT 783 00:31:55,920 --> 00:31:56,800 COULD BE USE FOR COMMUNITY. 784 00:31:56,800 --> 00:31:58,080 IN THE END, WHAT WE HAVE. 785 00:31:58,080 --> 00:31:59,720 WE HAVE A BIOMEDICAL MARKER 786 00:31:59,720 --> 00:32:00,240 REVOLUTION. 787 00:32:00,240 --> 00:32:02,080 ABILITY TO QUANTIFY ASPECTS OF 788 00:32:02,080 --> 00:32:02,640 AGING. 789 00:32:02,640 --> 00:32:03,880 TEST INTERVENTIONS. 790 00:32:03,880 --> 00:32:05,520 OPPORTUNITIES FOR MAJOR 791 00:32:05,520 --> 00:32:06,520 ADVANCES. 792 00:32:06,520 --> 00:32:09,200 YET WE HAVE MANY CHALLENGE AND I 793 00:32:09,200 --> 00:32:10,600 OUTLINED 10 CHALLENGE THIS IS MY 794 00:32:10,600 --> 00:32:13,520 SLIDES BUT I AM SURE THERE ARE 795 00:32:13,520 --> 00:32:14,480 MORE. 796 00:32:14,480 --> 00:32:16,000 THAT'S IT, THIS IS MY CURRENT 797 00:32:16,000 --> 00:32:16,160 LAB. 798 00:32:16,160 --> 00:32:20,360 I TOLD YOU, ABOUT SEVERAL 799 00:32:20,360 --> 00:32:21,960 STUDIES AND THEY HAVE BEEN DONE 800 00:32:21,960 --> 00:32:30,120 BY JESSE, ALEXEY, AND ALSO 801 00:32:30,120 --> 00:32:32,040 ALBERT AND OTHER PEOPLE 802 00:32:32,040 --> 00:32:34,160 CONTRIBUTED TO GO OTHER 803 00:32:34,160 --> 00:32:34,440 PROJECTS. 804 00:32:34,440 --> 00:32:37,120 THEY ARE FUNDED BY NIA AND OF 805 00:32:37,120 --> 00:32:38,920 COURSE, WE ARE GRATEFUL FOR THAT 806 00:32:38,920 --> 00:32:41,880 AND ALSO PREVIOUS LAB MEMBERS 807 00:32:41,880 --> 00:32:43,880 ALEX, DAVID AND MITCHELL ALSO 808 00:32:43,880 --> 00:32:49,160 THE KEY TO DEVELOPMENT OF CLOCKS 809 00:32:49,160 --> 00:32:50,320 AND ALSO THE APPLICATION. 810 00:32:50,320 --> 00:32:51,880 SO THANK YOU, VERY MUCH. 811 00:32:51,880 --> 00:32:54,280 THIS IS IS THE END OF MY 812 00:32:54,280 --> 00:32:55,000 PRESENTATION. 813 00:32:55,000 --> 00:32:57,960 AND I THINK WE COULD NOW MUCH 814 00:32:57,960 --> 00:33:00,240 SWITCH AND GO TO THE SECOND TALK 815 00:33:00,240 --> 00:33:02,040 AND REMEMBER THERE WILL BE NO 816 00:33:02,040 --> 00:33:03,240 QUESTIONS AFTER EACH TALK AND 817 00:33:03,240 --> 00:33:05,840 NEXT PRESENTER IS IS NAN HOA. 818 00:33:05,840 --> 00:33:08,520 ARE YOU READY? 819 00:33:08,520 --> 00:33:16,880 >>YES, YES. 820 00:33:16,880 --> 00:33:22,440 >>LET'S SEE. 821 00:33:22,440 --> 00:33:24,600 SO, I'M THE ORGANIZER FOR THE 822 00:33:24,600 --> 00:33:26,520 OPPORTUNITY SO IN THIS 823 00:33:26,520 --> 00:33:28,480 PRESENTATION, IN THIS TALK I 824 00:33:28,480 --> 00:33:32,120 WANT TO PRESENT OUR RECENT WORK, 825 00:33:32,120 --> 00:33:34,440 COM YOU TATE TIVE SINGLE CELL 826 00:33:34,440 --> 00:33:38,120 WITH MODEL TO UNDERSTAND HOW TO 827 00:33:38,120 --> 00:33:39,880 REGULATE AGING PROCESS AND 828 00:33:39,880 --> 00:33:41,520 IMPORTANT MODELS CAN BE USED TO 829 00:33:41,520 --> 00:33:43,400 GUIDE THE DESIGN OF 830 00:33:43,400 --> 00:33:45,080 INTERVENTIONS, TRAGEDIES TO PRO 831 00:33:45,080 --> 00:33:47,760 MOT LONGEVITY. 832 00:33:47,760 --> 00:33:51,280 SO, THE SYSTEM STUDY AND 833 00:33:51,280 --> 00:33:52,480 REPLICATING EMBEDDING USED THIS 834 00:33:52,480 --> 00:33:56,040 IS A GENETICALLY ATTRACTABLE 835 00:33:56,040 --> 00:33:57,840 MODEL FOR TEST IN MAMMALS SUCH 836 00:33:57,840 --> 00:34:00,200 AS STEM CELLS TO REPLICATE TIVE 837 00:34:00,200 --> 00:34:03,640 IS THE NUMBER OF MODERN CELL 838 00:34:03,640 --> 00:34:13,440 DIVISIONS BEFORE AND THE THAT 839 00:34:13,440 --> 00:34:17,640 INFLUENCE LONGEVITY AMONG NOT -- 840 00:34:17,640 --> 00:34:19,720 TO UNDERSTAND HOW THIS INTERACT 841 00:34:19,720 --> 00:34:22,000 WITH ONE ANOTHER AND HOW THIS 842 00:34:22,000 --> 00:34:23,760 INTERACTIONS CHANGE DYNAMICALLY 843 00:34:23,760 --> 00:34:27,680 TO DRIVE THE AGING PROCESS. 844 00:34:27,680 --> 00:34:30,120 SO WE DEVELOPED WISE WHICH TRAPS 845 00:34:30,120 --> 00:34:32,440 SINGLE MODERN CELLS AT THE 846 00:34:32,440 --> 00:34:36,160 BOTTOM OF FINGER SHIP CHAMBERS 847 00:34:36,160 --> 00:34:38,360 ALLOWING THEM TO BUFFED 848 00:34:38,360 --> 00:34:41,120 CONTINUOUSLY AND NOW THE SINGLE 849 00:34:41,120 --> 00:34:42,160 TIM LER AND WHOLE LOOK AT THE 850 00:34:42,160 --> 00:34:43,720 WHOLE AGING OF THE MOTHER CELL. 851 00:34:43,720 --> 00:34:47,680 THIS IS BUDDING AND TO EACH 852 00:34:47,680 --> 00:34:50,280 BUDDING GENERATIONS DOWNWARD AND 853 00:34:50,280 --> 00:34:52,440 STARTS AGAIN RATING THIS 854 00:34:52,440 --> 00:34:53,240 ELONGATED SUGGESTING THE MOTHER 855 00:34:53,240 --> 00:34:59,840 IS IS REALLY SICK AND EVENTUALLY 856 00:34:59,840 --> 00:35:00,640 IT WILL DIE. 857 00:35:00,640 --> 00:35:03,000 WE CAN TRACK THE CELLULAR 858 00:35:03,000 --> 00:35:06,880 CHANGES DURING A LARGE NUMBER OF 859 00:35:06,880 --> 00:35:09,120 SINGLE CELLS. 860 00:35:09,120 --> 00:35:12,320 THE ISOGENIC USE OF CELLS AND 861 00:35:12,320 --> 00:35:14,600 IT'S TWO DIFFERENT TYPESFUL 862 00:35:14,600 --> 00:35:15,720 CHANGES DURING AGING. 863 00:35:15,720 --> 00:35:17,960 HALF OF THE CELLS AND ALL THE 864 00:35:17,960 --> 00:35:19,600 ELONGATED DAUGHTERS BEFORE THAT 865 00:35:19,600 --> 00:35:23,640 WHILE ANOTHER HALF OF THE CELLS 866 00:35:23,640 --> 00:35:24,600 PRODUCE SMALL RUNT DAUGHTERS AND 867 00:35:24,600 --> 00:35:26,760 WE CALLED THEM MODE 1 AND MODE 2 868 00:35:26,760 --> 00:35:27,600 AGES. 869 00:35:27,600 --> 00:35:29,400 MODE 2 AGES FEATURED A MORE SLOW 870 00:35:29,400 --> 00:35:32,480 DOWN OF CELL SEPARATE AND THE 871 00:35:32,480 --> 00:35:35,600 SHELTER LIFESPAN COMPARED TO 872 00:35:35,600 --> 00:35:36,560 MODE 1 AGING. 873 00:35:36,560 --> 00:35:39,920 THEY FURTHER ATTRACT DIFFERENT 874 00:35:39,920 --> 00:35:43,080 AND OBSERVE THE NUCLEAR OLI 875 00:35:43,080 --> 00:35:45,320 BECAME ENLARGED AND FRAGMENTED 876 00:35:45,320 --> 00:35:47,320 YESTERDAY MODE 1 CELLS AND NOT 877 00:35:47,320 --> 00:35:52,960 IN MODE 2 CELLS AND THE MIKE OWE 878 00:35:52,960 --> 00:35:55,440 CHONDRIAL IS NOT IN MODE 1 CELLS 879 00:35:55,440 --> 00:35:58,080 SO THIS SHOWS THAT A DIFFERENT 880 00:35:58,080 --> 00:36:00,720 MODES OF AGING BY TARGETED 881 00:36:00,720 --> 00:36:07,440 DIFFERENT OREGON OREGON ELSE. 882 00:36:07,440 --> 00:36:10,240 THE AGING DEPEND ON THE NUCLEAR 883 00:36:10,240 --> 00:36:20,720 ENLARGEMENT IS RELATED IT'S 884 00:36:21,440 --> 00:36:23,760 SILENCING AND NOT MEDIATED BY A 885 00:36:23,760 --> 00:36:26,600 CONSERVE THE LIFE IN TWO 886 00:36:26,600 --> 00:36:28,800 REPRESSES RECOM BIN EIGHTING THE 887 00:36:28,800 --> 00:36:32,640 RDA AND THE MONITOR RDNA 888 00:36:32,640 --> 00:36:36,480 SILENCING IN CELLS WE PROMOTER 889 00:36:36,480 --> 00:36:40,840 AS RDNA REGION BECAUSE THE 890 00:36:40,840 --> 00:36:42,840 REPORTER IS REPRESSED BY 891 00:36:42,840 --> 00:36:46,800 SILENCING SO A DECREASE IND 892 00:36:46,800 --> 00:36:48,320 INDICATES IN-HOUSE AND SILENCING 893 00:36:48,320 --> 00:36:58,160 WHILE AN INCREASE REDUCES THOSE 894 00:36:58,160 --> 00:37:00,160 IT HAS BEEN PROPOSED THE 895 00:37:00,160 --> 00:37:02,760 DEFICIENCY OF A MAJOR FUNCTIONAL 896 00:37:02,760 --> 00:37:08,240 FORM OF ERA MAY BE A T FACTOR IN 897 00:37:08,240 --> 00:37:09,360 THE TRAPS DESCRIPTIONAL COMPLEX 898 00:37:09,360 --> 00:37:12,920 IS REQUIRED OF A MIGHT OWE CON 899 00:37:12,920 --> 00:37:15,880 AGREAL FUNCTION AND TO MONITOR 900 00:37:15,880 --> 00:37:17,960 DURING AIMING WE USE THE NUCLEAR 901 00:37:17,960 --> 00:37:21,440 AN CORED INFRARED. 902 00:37:21,440 --> 00:37:27,200 IT DEPENDS ON A DEGRADATION AND 903 00:37:27,200 --> 00:37:29,280 IT CORRELATES WITH CELLULAR 904 00:37:29,280 --> 00:37:31,880 LEVELS SO A HIGH SIGNAL HAS A 905 00:37:31,880 --> 00:37:34,480 LEVEL AND THE LOCAL IS IS IND 906 00:37:34,480 --> 00:37:38,440 INDICATES A LOW LEVEL AND SO TO 907 00:37:38,440 --> 00:37:40,040 DETERMINE HOW THOSE HAVE 908 00:37:40,040 --> 00:37:42,760 PATHWAYS, OPERATES, TOGETHER, TO 909 00:37:42,760 --> 00:37:45,000 DRIVE THE PROCESS INTRODUCE BOTH 910 00:37:45,000 --> 00:37:49,360 THE RDA AND GFR REPORTER INTO 911 00:37:49,360 --> 00:37:50,560 THE SAME CELLS. 912 00:37:50,560 --> 00:37:51,720 SIMULTANEOUSLY TRYING TO ASSERT 913 00:37:51,720 --> 00:37:54,360 TO HAVE ACTIVITIES DURING AGING. 914 00:37:54,360 --> 00:37:56,560 HERE IN THIS SLIDE, I'M GOING TO 915 00:37:56,560 --> 00:37:58,360 SHOW REP TENTATIVE MOVIES OF 916 00:37:58,360 --> 00:38:02,200 SINGLE AGING CELLS AND THE AGING 917 00:38:02,200 --> 00:38:03,400 TRAJECTORIES QUANTIFY FROM THIS. 918 00:38:03,400 --> 00:38:06,640 HERE IN THIS PREVIOUS SPACE, THE 919 00:38:06,640 --> 00:38:11,640 PERCENTAGE OF LIFETIME FROM 0% 920 00:38:11,640 --> 00:38:12,880 TO 100%. 921 00:38:12,880 --> 00:38:17,080 THE SIGNAL AND THE RDNA SIGNAL. 922 00:38:17,080 --> 00:38:21,360 LET'S START WITH THE CELL. 923 00:38:21,360 --> 00:38:22,680 AS WE CAN SEE DURING THE CELLS 924 00:38:22,680 --> 00:38:24,720 SHOWED THE GRADUALLY INCREASED 925 00:38:24,720 --> 00:38:28,600 THE SIGNAL AND NUCLEAR IRP 926 00:38:28,600 --> 00:38:28,840 SIGNAL. 927 00:38:28,840 --> 00:38:31,640 SO, NOW LET'S LOOK AT THE MODE 2 928 00:38:31,640 --> 00:38:32,680 CELLS. 929 00:38:32,680 --> 00:38:34,320 VERY DIFFERENT FROM MODE 1 CELLS 930 00:38:34,320 --> 00:38:41,240 WHICH SEE A SHARP DEPLETION. 931 00:38:41,240 --> 00:38:43,240 SO NEXT LET'S LOOK AT THE WHOLE 932 00:38:43,240 --> 00:38:44,640 POPULATION OF EYE OWE AGAIN I 933 00:38:44,640 --> 00:38:47,000 CAN CELLS AND HERE THE RIGHT 934 00:38:47,000 --> 00:38:49,600 IMPORTANCE I FOUND THOSE CELLS 935 00:38:49,600 --> 00:38:53,720 AND THE BLUE ARE FROM MODE 2 936 00:38:53,720 --> 00:38:58,040 CELLS AND WE CAN FURTHER PROJECT 937 00:38:58,040 --> 00:39:01,800 THE INITIAL STAGE OF OLDER CELLS 938 00:39:01,800 --> 00:39:03,600 AND THE TRAJECTORIES CAN BE 939 00:39:03,600 --> 00:39:05,680 SHOWING YOU THE SPACE AND THE 940 00:39:05,680 --> 00:39:07,800 STATES OF OLDER CELLS CAN BE 941 00:39:07,800 --> 00:39:09,080 PROJECTED OF ANOTHER CELL AS WE 942 00:39:09,080 --> 00:39:15,840 CAN SEE HERE, ISOGENIC CELLS 943 00:39:15,840 --> 00:39:17,240 TIGER WOODS REPORTERS THEY WORK 944 00:39:17,240 --> 00:39:19,520 EARLIER IN LIFE AND PROGRESS 945 00:39:19,520 --> 00:39:23,680 OVER TWO DIRECTIONS AND MODE 1 946 00:39:23,680 --> 00:39:25,320 AGING ENDING THEIR LIES WITH A 947 00:39:25,320 --> 00:39:29,080 LOWER TO HIGH STATE COP CYSTS OF 948 00:39:29,080 --> 00:39:32,160 NUCLEAR OLDER DECLINE AND MODE 2 949 00:39:32,160 --> 00:39:36,680 AGING ENDED WITH LOW STAGE 950 00:39:36,680 --> 00:39:39,240 CONSISTS IN THE -- THIS RESULTS 951 00:39:39,240 --> 00:39:43,520 REALLY SHOW THAT IDENTICAL CELLS 952 00:39:43,520 --> 00:39:47,680 AGE TOWARDS DISCRETE STAGE WITH 953 00:39:47,680 --> 00:39:49,440 UNCORRELATED ACTIVITIES 954 00:39:49,440 --> 00:39:51,240 SUGGESTING POTENTIAL INHIBITION 955 00:39:51,240 --> 00:39:52,920 BETWEEN CIRCLE AND A HALF THAT 956 00:39:52,920 --> 00:39:56,840 IS EARLIER LIFE OF THE ORGANS OF 957 00:39:56,840 --> 00:39:57,280 AGING. 958 00:39:57,280 --> 00:40:00,000 WE CONFIRM THAT THIS ANALYSIS 959 00:40:00,000 --> 00:40:04,760 AND IN ADDITION TO THAT, THEY 960 00:40:04,760 --> 00:40:07,040 START TO HAVE REGULATIONS FROM 961 00:40:07,040 --> 00:40:08,000 THE PREVIOUS. 962 00:40:08,000 --> 00:40:11,320 BASED ON THIS, WE DEVELOPED A 963 00:40:11,320 --> 00:40:13,440 SIMPLE METH MAD CAL MODEL 964 00:40:13,440 --> 00:40:15,240 SIMULATING HOW THEY HAVE CHANGED 965 00:40:15,240 --> 00:40:17,840 DURING AGING. 966 00:40:17,840 --> 00:40:23,280 WE CAN INHIBITION AS WELL AS THE 967 00:40:23,280 --> 00:40:24,240 ULTRA-REGULATION. 968 00:40:24,240 --> 00:40:26,480 TO MAKE THINGS EASIER, THE LESS 969 00:40:26,480 --> 00:40:33,480 TARGET THE SYSTEM FOR FOR 970 00:40:33,480 --> 00:40:34,160 INHIBITION. 971 00:40:34,160 --> 00:40:37,120 THIS IS A MODEL SIMULATION 972 00:40:37,120 --> 00:40:40,040 SHOWING HOW HAP CHANGES OVER 973 00:40:40,040 --> 00:40:40,320 TIME. 974 00:40:40,320 --> 00:40:42,560 THESE ARROWS POINT TO THE 975 00:40:42,560 --> 00:40:43,760 DIRECTION WHERE THE SYSTEM IS 976 00:40:43,760 --> 00:40:44,680 MOVING TOWARDS. 977 00:40:44,680 --> 00:40:49,240 THIS BLUE HORIZONTAL LINES ARE 978 00:40:49,240 --> 00:40:52,400 CALLED SIR 2, THE CHANGE IS 979 00:40:52,400 --> 00:40:54,040 ZERO. 980 00:40:54,040 --> 00:40:56,320 THIS RIGHT ARE HAN MEANING THE 981 00:40:56,320 --> 00:40:59,080 RATE OF CHANGE OF HAP IS ZERO ON 982 00:40:59,080 --> 00:41:00,760 THESE LINES. 983 00:41:00,760 --> 00:41:03,640 AND WHERE THEY INTERSECT, IT'S 984 00:41:03,640 --> 00:41:05,480 CIRCLES ARE CALLED UNSTABLE 985 00:41:05,480 --> 00:41:07,640 FIXED POINTS. 986 00:41:07,640 --> 00:41:08,240 THESE ARE THE POINTS THAT THE 987 00:41:08,240 --> 00:41:10,200 SYSTEM WILL ESCAPE FROM. 988 00:41:10,200 --> 00:41:13,600 THIS CLOSE TO THE CIRCLE AS 989 00:41:13,600 --> 00:41:14,560 STABLE THESE ARE THE POINTS 990 00:41:14,560 --> 00:41:18,040 WHERE THE SYSTEM WILL GO TOWARDS 991 00:41:18,040 --> 00:41:19,560 AND THE SYSTEM REACH THESE 992 00:41:19,560 --> 00:41:21,240 POINTS THEY WILL STOP THERE. 993 00:41:21,240 --> 00:41:23,240 SO HERE DEPENDING ON WHERE THE 994 00:41:23,240 --> 00:41:25,280 SYSTEM STARTS, IT CAN MOVE TO 995 00:41:25,280 --> 00:41:28,640 WHERE THE FOUR DIFFERENT STEADY 996 00:41:28,640 --> 00:41:30,120 STATES, THE SLOW STATES AND THE 997 00:41:30,120 --> 00:41:32,480 HIGHS START TO LOW STATE AND THE 998 00:41:32,480 --> 00:41:37,160 LOW START TO HIGH STATE AND SO 999 00:41:37,160 --> 00:41:41,480 IF THE CASE OF CELLS, WHEN THE 1000 00:41:41,480 --> 00:41:49,960 INHIBITION IS ADDED THE THE IN-- 1001 00:41:49,960 --> 00:41:52,040 IN THIS REGION ELIMINATES THE 1002 00:41:52,040 --> 00:41:55,000 STABLE FIXED PARTS AND TO 1003 00:41:55,000 --> 00:41:58,360 ADDRESS THE NATURE OF AGING IN 1004 00:41:58,360 --> 00:42:00,720 SINGLE CELLS, THEY HAVE WORK OF 1005 00:42:00,720 --> 00:42:03,720 OUR MODEL AND COMMUTED A 1006 00:42:03,720 --> 00:42:06,080 POTENTIAL LANDSCAPE AND SOLVING 1007 00:42:06,080 --> 00:42:09,680 THE CORRESP CORRESPONDENCE AND F 1008 00:42:09,680 --> 00:42:11,560 THOSE STABLE FIX POINTS OF THE 1009 00:42:11,560 --> 00:42:14,040 DETERMINISTIC SYSTEM CORRESPONDS 1010 00:42:14,040 --> 00:42:16,080 TO A LOCAL VEIL ON THE LANDSCAPE 1011 00:42:16,080 --> 00:42:20,640 WITH REFLECTING PROBABILITY. 1012 00:42:20,640 --> 00:42:22,680 THE HIGHER THE PROBABILITY AND 1013 00:42:22,680 --> 00:42:25,040 IN THIS WAY, AGING OF EACH 1014 00:42:25,040 --> 00:42:30,760 SINGLE CELL CAN BE VIEWED AS A 1015 00:42:30,760 --> 00:42:35,640 FOR DIFFERENT VALUES ON THE 1016 00:42:35,640 --> 00:42:39,200 LANDSCAPE. 1017 00:42:39,200 --> 00:42:41,280 IT CORRESPONDS TO THE LOW HAP1 1018 00:42:41,280 --> 00:42:45,440 AND THE ANNUAL STAGE OF MODE 2 1019 00:42:45,440 --> 00:42:45,880 AGING. 1020 00:42:45,880 --> 00:42:51,120 WE FURTHER PERFORM THE GENETIC 1021 00:42:51,120 --> 00:42:51,720 AND TWO-FOLD OVER EXPRESSION 1022 00:42:51,720 --> 00:42:53,120 START TO SHOW THE VERY 1023 00:42:53,120 --> 00:42:54,120 INTERESTING RESULTS. 1024 00:42:54,120 --> 00:42:56,960 IN ADDITION TO MODE ONE AND MODE 1025 00:42:56,960 --> 00:42:59,160 TWO AGING, SO TO OVER EXPRESSION 1026 00:42:59,160 --> 00:43:01,840 GENERATED A NEW MODE OF THAT 1027 00:43:01,840 --> 00:43:05,160 HAVE ENDED WITH A HIGH STATE AND 1028 00:43:05,160 --> 00:43:12,840 WE CALL IT THE STORY AGING IT 1029 00:43:12,840 --> 00:43:14,680 CAN NORMAL CELLS SEPARATE 1030 00:43:14,680 --> 00:43:16,040 THROUGHOUT THE ENTIRE LIFESPAN 1031 00:43:16,040 --> 00:43:17,920 AND VERY DIFFERENT FROM MODE ONE 1032 00:43:17,920 --> 00:43:24,640 AND MODE TWO CELLS. 1033 00:43:24,640 --> 00:43:25,720 OUR MODEL IS INTEREST BY 1034 00:43:25,720 --> 00:43:28,280 TWO-FOLD AND IT'S INCREASED 1035 00:43:28,280 --> 00:43:30,400 ACTIVITY CAN PARTIALLY 1036 00:43:30,400 --> 00:43:31,960 COUNTERACT THE INHIBITION 1037 00:43:31,960 --> 00:43:34,680 LEADING TO THE EMERGENCE OF A 1038 00:43:34,680 --> 00:43:37,640 NEW STABLE FIX ON THE AND THE 1039 00:43:37,640 --> 00:43:40,800 NUS VEIL ON THE LANDSCAPE. 1040 00:43:40,800 --> 00:43:44,440 SO THE TOWARDS THESE HIGH HAP 1041 00:43:44,440 --> 00:43:45,640 STATES CORRESPONDS TO THE AGING 1042 00:43:45,640 --> 00:43:49,280 THAT WILL BE OBSERVED 1043 00:43:49,280 --> 00:43:49,760 EXPERIMENTALLY. 1044 00:43:49,760 --> 00:43:52,360 UNDER THE GUIDANCE OF OUR MODEL, 1045 00:43:52,360 --> 00:43:54,760 WE FURTHER PERFORMED ADDITIONAL 1046 00:43:54,760 --> 00:43:57,600 GENETIC MANIPULATIONS AND WE 1047 00:43:57,600 --> 00:43:59,680 REACHED THE LARGE FRACTION OF 1048 00:43:59,680 --> 00:44:02,960 CELLS WHO EFFECTIVELY PROMOTE 1049 00:44:02,960 --> 00:44:04,040 LONGEVITY OF THE WHOLE 1050 00:44:04,040 --> 00:44:04,880 POPULATION AND I DON'T HAVE TIME 1051 00:44:04,880 --> 00:44:08,560 TO TALK ABOUT THAT IN DETAIL 1052 00:44:08,560 --> 00:44:09,840 TODAY, INSTEAD I WILL FOCUS ON 1053 00:44:09,840 --> 00:44:17,640 OUR MOST RECENT UNPUBLISHED 1054 00:44:17,640 --> 00:44:24,680 REPORT SO LET'S GO BACK TO OUR 1055 00:44:24,680 --> 00:44:25,600 MAUD AND IT'S EACH SINGLE CELL 1056 00:44:25,600 --> 00:44:30,720 CAN BE VIEWED AS THEY WERE 1057 00:44:30,720 --> 00:44:35,400 GENERATION FOR A DIFFERENT 1058 00:44:35,400 --> 00:44:37,760 STEADY STATES AND AND THE LOW 1059 00:44:37,760 --> 00:44:41,080 START TO HIGH HALF STATES LEADED 1060 00:44:41,080 --> 00:44:51,440 TO NUCLEAR AND THE. 1061 00:45:01,120 --> 00:45:03,440 >>WE TRY TO HAVE FROM THE 1062 00:45:03,440 --> 00:45:05,520 INHIBITION TO FEEDBACK LOOP AND 1063 00:45:05,520 --> 00:45:07,720 IT CAN LEADS TO SUSTAIN 1064 00:45:07,720 --> 00:45:16,640 OSCILLATIONS IN THE LEVELS AND 1065 00:45:16,640 --> 00:45:19,280 IN WHICH THE SYSTEM KEEPS MOVING 1066 00:45:19,280 --> 00:45:20,800 ALONG THIS BLACK CIRCLE AND WILL 1067 00:45:20,800 --> 00:45:31,240 NEVER COMMIT TO THE AND. 1068 00:45:37,720 --> 00:45:43,360 >>BY HALF AND HALF OF IT TOO 1069 00:45:43,360 --> 00:45:46,320 WITH A PROPER VALUES THIS MODEL 1070 00:45:46,320 --> 00:45:50,680 CAN PRODUCE SUSTAIN OSCILLATIONS 1071 00:45:50,680 --> 00:45:56,040 IN CERTAIN LEVELS AND THE 1072 00:45:56,040 --> 00:46:01,880 SIMULATION AND ON THE BATTLE AND 1073 00:46:01,880 --> 00:46:04,320 WE FOUND THAT OSCILLATIONS ARE 1074 00:46:04,320 --> 00:46:08,600 FAVORED BY A STRONG INDUCTION OF 1075 00:46:08,600 --> 00:46:17,000 BY HALF AND THIS WILL SEARCH AS 1076 00:46:17,000 --> 00:46:27,200 HERE ANDS. 1077 00:46:39,520 --> 00:46:49,960 >>TO ENABLE A REPRESSION AND 1078 00:47:05,400 --> 00:47:08,400 INTO A FEEDBACK LOOP. 1079 00:47:08,400 --> 00:47:10,680 THESE ABUNDANCE IN 1080 00:47:10,680 --> 00:47:12,280 REPRESENTATIVE CELLS AND WE 1081 00:47:12,280 --> 00:47:14,160 OBSERVED THAT ALMOST OLD 1082 00:47:14,160 --> 00:47:16,160 ENGINEER CELLS SHOWED 1083 00:47:16,160 --> 00:47:18,320 OSCILLATIONS DURING AGING AND 1084 00:47:18,320 --> 00:47:21,160 THE CONTROL CELLS SHOW SUCH OLE 1085 00:47:21,160 --> 00:47:21,760 ISATIONS. 1086 00:47:21,760 --> 00:47:26,160 AND THE IMPORTANTLY, OUR 1087 00:47:26,160 --> 00:47:27,200 OSCILLATING SHOWED DRAMATICALLY 1088 00:47:27,200 --> 00:47:30,640 A END ITING THE LIFESPAN AND 1089 00:47:30,640 --> 00:47:32,400 WITH 8% INCREASE COMPARED OF 1090 00:47:32,400 --> 00:47:34,200 THAT THE CELLS AND THIS IS THE 1091 00:47:34,200 --> 00:47:44,680 MOST PRONOUNCED IT SHOWS THE 1092 00:47:56,760 --> 00:47:58,920 LONGEST LIFESPAN AND IN ADDITION 1093 00:47:58,920 --> 00:48:01,080 OUR OSCILLATOR SHOWED A FASTER 1094 00:48:01,080 --> 00:48:03,760 CELL SEPARATE COMPARED TO THE 1095 00:48:03,760 --> 00:48:05,320 OTHER LONG LIVED MUTANTS END 1096 00:48:05,320 --> 00:48:07,120 INDICATING THAT IT HAS A 1097 00:48:07,120 --> 00:48:09,840 HEALTHIER CELLULAR STATE DURING 1098 00:48:09,840 --> 00:48:10,240 AGING. 1099 00:48:10,240 --> 00:48:20,680 SO BASED ON OUR MODEL, IT 1100 00:48:21,680 --> 00:48:26,760 PREVENTS CELLS WHO DEPLETION SO 1101 00:48:26,760 --> 00:48:29,680 THEY MONITOR THE RNDA I'LLENS 1102 00:48:29,680 --> 00:48:33,120 AND THE ABUNDANCE IN THE OS 1103 00:48:33,120 --> 00:48:36,520 LATER CELLS USING THE NUCLEAR 1104 00:48:36,520 --> 00:48:38,600 REPORTER THAT WE INTRODUCED 1105 00:48:38,600 --> 00:48:38,880 PREVIOUSLY. 1106 00:48:38,880 --> 00:48:43,160 HERE IN THIS MAP, EACH ROW 1107 00:48:43,160 --> 00:48:44,440 REPRESENTS THE TIME TRAY OF A 1108 00:48:44,440 --> 00:48:45,760 SINGLE CELL THROUGHOUT THE 1109 00:48:45,760 --> 00:48:47,040 ENTIRE LIFESPAN. 1110 00:48:47,040 --> 00:48:50,800 THE COLOR REPRESENTS THE 1111 00:48:50,800 --> 00:48:52,320 INTENSITY. 1112 00:48:52,320 --> 00:48:54,560 IT IT TWO SHOW FLUORESCENT 1113 00:48:54,560 --> 00:48:56,800 CHANGES OF THE TWO REPORTERS 1114 00:48:56,800 --> 00:48:58,920 FROM THE SAME CELLS AND VERY 1115 00:48:58,920 --> 00:49:02,000 SIMILAR TO WHAT WE SHOWED 1116 00:49:02,000 --> 00:49:03,680 BEFORE, ABOUT HALF OF THE CELLS 1117 00:49:03,680 --> 00:49:06,760 ARE COMMITTED TO MODE AND ENDED 1118 00:49:06,760 --> 00:49:10,400 THEIR LIFE WITH A CONTINUOUS 1119 00:49:10,400 --> 00:49:12,080 SILENCING MODELS AND THE OTHERS 1120 00:49:12,080 --> 00:49:14,040 ARE COMMITTED AND ENDED THEIR 1121 00:49:14,040 --> 00:49:17,440 LIVES WITH A PRONOUNED 1122 00:49:17,440 --> 00:49:17,680 DEPLETION. 1123 00:49:17,680 --> 00:49:23,520 IN CONTRAST, THE MAJORITY OF THE 1124 00:49:23,520 --> 00:49:26,560 OLE OS LATER CELLS SHOWS PULSES 1125 00:49:26,560 --> 00:49:30,600 OF RNDA AND SIGNALS THROUGHOUT 1126 00:49:30,600 --> 00:49:36,360 THEIR ENTIRE LIFESPAN WITHOUT A 1127 00:49:36,360 --> 00:49:38,880 TO EITHER (INAUDIBLE) SO THIS 1128 00:49:38,880 --> 00:49:42,760 RESULTS WERE CONSISTENT WITH OUR 1129 00:49:42,760 --> 00:49:44,440 PREDICTION DEMONSTRATING THAT 1130 00:49:44,440 --> 00:49:48,080 THE OSCILLATOR CAN ENABLE A 1131 00:49:48,080 --> 00:49:51,280 BALANCE BETWEEN RDNA SILENCING 1132 00:49:51,280 --> 00:49:54,440 AND THEREFORE IT PROMOTE LON 1133 00:49:54,440 --> 00:50:00,000 GEOFF TLONGEVITY, I HOPE OUR STS 1134 00:50:00,000 --> 00:50:02,040 PROVIDE A CONVINCING EXAMPLE TO 1135 00:50:02,040 --> 00:50:03,560 SHOWCASE THE POWER OF SYSTEM 1136 00:50:03,560 --> 00:50:05,120 BIOLOGY AND COMPUTATIONAL 1137 00:50:05,120 --> 00:50:07,600 APPROACHES FOR ENABLING NEW 1138 00:50:07,600 --> 00:50:09,600 DISCOVERIES IN AGING BIOLOGY. 1139 00:50:09,600 --> 00:50:12,760 AND THE IMPORTANTLY, I WANT TO 1140 00:50:12,760 --> 00:50:14,400 HIGHLIGHT THE FRAMEWORK THAT WE 1141 00:50:14,400 --> 00:50:17,440 ESTABLISHED THROUGH THIS WORK 1142 00:50:17,440 --> 00:50:19,120 CENTERS ON EFFECT IT TIVE 1143 00:50:19,120 --> 00:50:23,200 INTEGRATION OF EXPERIMENT AND ED 1144 00:50:23,200 --> 00:50:24,840 MODELING THAT CAN DRIVE 1145 00:50:24,840 --> 00:50:28,120 INNOVATIONS IN INTERVENTION 1146 00:50:28,120 --> 00:50:28,560 DEVELOPMENT. 1147 00:50:28,560 --> 00:50:29,920 FINALLY I WANT TO ACKNOWLEDGE 1148 00:50:29,920 --> 00:50:32,920 OUR COLLABORATOR, JEFF, LAUREN 1149 00:50:32,920 --> 00:50:34,720 AND LANCE OVER THE PAST SEVEN 1150 00:50:34,720 --> 00:50:40,120 YEARS WE HAVE BEEN WORKING VERY 1151 00:50:40,120 --> 00:50:42,000 CLOSELY TOGETHER AND AGING AND 1152 00:50:42,000 --> 00:50:44,360 OUR CURRENT GOAL IS TO EXPAND 1153 00:50:44,360 --> 00:50:47,680 OUR APPROACH TO STUDY THE 1154 00:50:47,680 --> 00:50:49,720 DYNAMICS IN THE CELL AGING AND I 1155 00:50:49,720 --> 00:50:52,040 ALSO WANT TO THANK NIA FOR THE 1156 00:50:52,040 --> 00:50:53,840 SUPPORT TO OUR EFFORTS. 1157 00:50:53,840 --> 00:50:55,400 SOL, THANK YOU, VERY MUCH FOR 1158 00:50:55,400 --> 00:50:58,320 YOUR ATTENTION. 1159 00:50:58,320 --> 00:50:59,280 >>THANK YOU. 1160 00:50:59,280 --> 00:51:01,840 THIS IS REALLY GREAT. 1161 00:51:01,840 --> 00:51:04,600 AMAZING DISCOVERY. 1162 00:51:04,600 --> 00:51:07,960 CURRENTLY, WE HAVE 1:06 AND THE 1163 00:51:07,960 --> 00:51:09,320 NEXT -- WE HAVE A 10 MINUTE 1164 00:51:09,320 --> 00:51:10,600 BREAK SO LET'S BREAK FOR 10 1165 00:51:10,600 --> 00:51:12,520 MINUTES AND THEN WE WILL STARTED 1166 00:51:12,520 --> 00:51:14,880 A FEW MINUTES EARLY JUST EX 1167 00:51:14,880 --> 00:51:17,480 EXACTLY 10 MINUTES FROM NOW. 1168 00:51:17,480 --> 00:51:17,680 1:16. 1169 00:51:17,680 --> 00:51:18,760 THANK YOU, EVERYBODY. 1170 00:51:18,760 --> 00:51:21,240 >>LET'S BEGIN THE 1171 00:51:21,240 --> 00:51:22,880 SECOND PART OF SESSION ONE. 1172 00:51:22,880 --> 00:51:33,320 OUR NEXT SPEAKER IS PAOLA 1173 00:51:35,160 --> 00:51:35,400 SEBASTIANI. 1174 00:51:35,400 --> 00:51:37,200 >>THANK YOU FOR THE OPPORTUNITY 1175 00:51:37,200 --> 00:51:39,320 TO PRESENT THIS WORKSHOP AND I'M 1176 00:51:39,320 --> 00:51:41,000 GOING TO TALK ABOUT 1177 00:51:41,000 --> 00:51:42,160 COMPUTATIONAL CHALLENGES IN 1178 00:51:42,160 --> 00:51:47,040 STUDIES OF EXTREME LONGEVITY SO 1179 00:51:47,040 --> 00:51:50,840 I'M SWITCH TO GO TALK ABOUT OLD 1180 00:51:50,840 --> 00:52:01,360 PEOPLE AND EXTREMELY OLD PEOPLE 1181 00:52:02,960 --> 00:52:05,960 MORE THAN 200 PEOPLE PAST THE 1182 00:52:05,960 --> 00:52:08,240 AIMING OF 110 AND THE LONGER 1183 00:52:08,240 --> 00:52:14,080 FAMILY STUDIES AT NIH STUDY WITH 1184 00:52:14,080 --> 00:52:16,680 SINGLE GEOFF TEE AND AS A ROLE 1185 00:52:16,680 --> 00:52:27,240 OF 350 FAMILIES AND SUBJECTS AND 1186 00:52:27,960 --> 00:52:32,840 WITH A ROLE OF 1400 SEN TIN AR 1187 00:52:32,840 --> 00:52:35,320 ANS IN THEIR OFFSPRING AND WE'RE 1188 00:52:35,320 --> 00:52:42,880 MAKING MAJOR EFFORTS AN AND IT'A 1189 00:52:42,880 --> 00:52:47,720 SMALLER STUDY AND THE GOAL IS TO 1190 00:52:47,720 --> 00:52:50,640 ENROLL 350 CENTENARIANS AND ON 1191 00:52:50,640 --> 00:52:53,160 THE STUDY, THE RELATIVES THE 1192 00:52:53,160 --> 00:52:56,520 GOAL IS TO COLLECT BIOLOGICAL 1193 00:52:56,520 --> 00:52:57,480 SAMPLES, MOST OF THE STUDIES 1194 00:52:57,480 --> 00:53:00,120 HAVE A UNIFORM THEY COLLECT 1195 00:53:00,120 --> 00:53:02,840 BLOOD SAMPLES FOR DNA STRUCTURE 1196 00:53:02,840 --> 00:53:06,760 AND GENETIC STUDIES AND TRANCE 1197 00:53:06,760 --> 00:53:10,280 TOPIC STUDY AND PLASMA AND 1198 00:53:10,280 --> 00:53:14,040 LONGEVITY OMICS IS ADDED A 1199 00:53:14,040 --> 00:53:17,400 COMPONENT OF THE MICROBIOME WITH 1200 00:53:17,400 --> 00:53:19,040 SAMPLES THAT IS ON GOING. 1201 00:53:19,040 --> 00:53:22,240 IN ADDITION, ALL THE STUDIES AND 1202 00:53:22,240 --> 00:53:25,000 DATA COLLECTIONS SO WE COLLECT A 1203 00:53:25,000 --> 00:53:29,240 LOT OF DATA ON VICTIMS AND MANY 1204 00:53:29,240 --> 00:53:30,400 AGING TRAITS AND THE 1205 00:53:30,400 --> 00:53:31,560 PARTICIPANTS HAVE FOLLOWED 1206 00:53:31,560 --> 00:53:34,000 ANNUALLY AND SO FAR, IN TERMS OF 1207 00:53:34,000 --> 00:53:38,640 OMICS, WE HAVE GENERATED GENOME 1208 00:53:38,640 --> 00:53:42,000 DATA AND GENOME SEQUENCING 1209 00:53:42,000 --> 00:53:48,040 PARTICIPANTS IN THE NEXT WE HAVE 1210 00:53:48,040 --> 00:53:50,200 GENERATED MET TABLOMICS AND WE 1211 00:53:50,200 --> 00:53:52,320 HAVE MUCH MORE DATA AND GENOME 1212 00:53:52,320 --> 00:53:58,880 SEQUENCES ON EVERYBODY AND ON 1213 00:53:58,880 --> 00:54:02,120 MORE THAN 2,000 PARTICIPANTS AND 1214 00:54:02,120 --> 00:54:07,520 ALSO RNA DATA AND WE'RE 1215 00:54:07,520 --> 00:54:11,560 GENERATING DATA ON A FEW HOW 1216 00:54:11,560 --> 00:54:12,680 PARTICIPANTS IN SEQUENCING SO 1217 00:54:12,680 --> 00:54:15,040 THERE'S A LOT OF THAT WE'RE 1218 00:54:15,040 --> 00:54:16,440 COLLECT AND A LOT OF DATA THAT 1219 00:54:16,440 --> 00:54:17,400 WE'LL GENERATE IN THE NEXT 1220 00:54:17,400 --> 00:54:19,000 COUPLE OF YEARS AND ONE OF THE 1221 00:54:19,000 --> 00:54:21,600 QUESTIONS WHY DO WE LOOK AT 1222 00:54:21,600 --> 00:54:24,040 CENTENARIANS AND WHEN WE LOOK, 1223 00:54:24,040 --> 00:54:31,040 WE COLLECT ALL THE OMICS DATA. 1224 00:54:31,040 --> 00:54:41,440 SO IN THE -- IN ACCIDENT 1225 00:54:43,120 --> 00:54:44,680 PHYSICAL AND COGNITIVE 1226 00:54:44,680 --> 00:54:45,960 CONDITIONS AND THEY MAINTAIN THE 1227 00:54:45,960 --> 00:54:48,960 PHYSICAL AND COGNITIVE FUNCTIONS 1228 00:54:48,960 --> 00:54:50,360 TO THE INTRODUCTION OF THE 1229 00:54:50,360 --> 00:54:54,000 LIFESPAN AND THE FISH YOU AND 1230 00:54:54,000 --> 00:54:56,280 GENETICS AND UNMODIFIABLE RISK 1231 00:54:56,280 --> 00:54:58,200 FACTORS SO IF YOU HAVE IDENTIFY 1232 00:54:58,200 --> 00:54:59,720 THE GENETIC MUTATION THAT'S 1233 00:54:59,720 --> 00:55:02,200 ALLOW PEOPLE TO LIVE LONGER, THE 1234 00:55:02,200 --> 00:55:05,120 ONLY SOLUTION FOR EVERYBODY TO 1235 00:55:05,120 --> 00:55:05,720 CHOSE YOUR PARENTS WELL. 1236 00:55:05,720 --> 00:55:12,320 WE CAN'T REALLY DO SO IN THE 1237 00:55:12,320 --> 00:55:15,680 FAST FEW YEARS AND TRANSLATION 1238 00:55:15,680 --> 00:55:20,160 OF THESE GENETICS AND THE GOAL 1239 00:55:20,160 --> 00:55:25,520 IS TO IDENTIFY THIS MOL IKE LAR 1240 00:55:25,520 --> 00:55:34,320 THAT IS AND TRY TO UNDERSTAND 1241 00:55:34,320 --> 00:55:35,800 THE PROTECTED CORRELATED ARE 1242 00:55:35,800 --> 00:55:38,400 HAVING THE GOOD GENETIC 1243 00:55:38,400 --> 00:55:43,320 MUTATIONS AND MOLECULAR CAN BE 1244 00:55:43,320 --> 00:55:46,760 MODIFIED SO THE WHOLE PLAN HERE, 1245 00:55:46,760 --> 00:55:47,960 THIS SUGGESTS THAT WHAT WE'RE 1246 00:55:47,960 --> 00:55:50,120 TRYING DO IS TO IDENTIFY TARGETS 1247 00:55:50,120 --> 00:55:55,960 FOR INTERVENTIONS FOR ANTIAGING 1248 00:55:55,960 --> 00:55:56,440 THERAPEUTICS. 1249 00:55:56,440 --> 00:55:59,160 THE PROBLEM, HOWEVER, IS 1250 00:55:59,160 --> 00:56:00,000 COMPLICATE AND WHAT WE'RE TRYING 1251 00:56:00,000 --> 00:56:04,600 TO DO IS BE IN ORDER TO IDENTIFY 1252 00:56:04,600 --> 00:56:05,880 GOOD INTERCEPTIONS WE'RE TRYING 1253 00:56:05,880 --> 00:56:08,680 TO BUILD MODEL THAT'S CAN 1254 00:56:08,680 --> 00:56:11,240 CONNECT ALL THESE THINGS 1255 00:56:11,240 --> 00:56:12,560 TOGETHER SO WE CAN USE IT FOR 1256 00:56:12,560 --> 00:56:15,840 UNDERSTANDING MECHANISMS 1257 00:56:15,840 --> 00:56:18,640 PREDICTING OUTCOMES AND WE HAD 1258 00:56:18,640 --> 00:56:23,320 PREDICT MORE THAN ONE THING AT 1259 00:56:23,320 --> 00:56:26,360 ONCE. 1260 00:56:26,360 --> 00:56:30,360 AND SO, WHERE ARE WE NOW? 1261 00:56:30,360 --> 00:56:32,440 SO FAR, WE HAVE COLLECTED PIECES 1262 00:56:32,440 --> 00:56:37,000 OF PUZZLE FOR AGAIN THE TICKS WE 1263 00:56:37,000 --> 00:56:38,560 A GROWING CATALOG ASSOCIATED 1264 00:56:38,560 --> 00:56:43,080 WITH THEM, THE ABILITY OF PEOPLE 1265 00:56:43,080 --> 00:56:44,680 TO LIVE TO OLD AGES. 1266 00:56:44,680 --> 00:56:47,200 WE ARE WILL BE STARTING TO 1267 00:56:47,200 --> 00:56:49,520 COLLECT PROTECTIVE VARIANTS THAN 1268 00:56:49,520 --> 00:56:52,720 CORRELATE WITH THE ABILITY OF 1269 00:56:52,720 --> 00:56:55,920 CENTENARIANS TO AGE, MAINTAINING 1270 00:56:55,920 --> 00:56:57,320 GOOD COGNITIVE FUNCTION AND JUST 1271 00:56:57,320 --> 00:56:59,960 TWO WEEKS AGO WE PUBLISHED THIS 1272 00:56:59,960 --> 00:57:01,840 ARTICLE THAT IDENTIFIED 1273 00:57:01,840 --> 00:57:04,080 PROTECTIVE VARIANTS THAT ALLOW 1274 00:57:04,080 --> 00:57:06,560 INDIVIDUALS TO AGE, MAINTAINING 1275 00:57:06,560 --> 00:57:08,080 GOOD PROCESSING SPEED. 1276 00:57:08,080 --> 00:57:13,960 AND SO THERE'S MUCH MORE THAT WE 1277 00:57:13,960 --> 00:57:15,720 ARE DISCOVERING AND WE WOULD BE 1278 00:57:15,720 --> 00:57:16,240 PUBLISHING SOON. 1279 00:57:16,240 --> 00:57:17,720 WE HAVE CONNECTED THESE DOTS 1280 00:57:17,720 --> 00:57:18,040 HERE. 1281 00:57:18,040 --> 00:57:23,160 WE HAVE IDENTIFIED MOLECULAR 1282 00:57:23,160 --> 00:57:25,200 SIGNATURES OF THE GENETIC 1283 00:57:25,200 --> 00:57:27,800 VARIANTS WITH LONGEVITY WE HAVE 1284 00:57:27,800 --> 00:57:29,880 IDENTIFIED MOLECULAR SIGNATURE 1285 00:57:29,880 --> 00:57:34,520 OF THE ALLELE THAT IS ALSO 1286 00:57:34,520 --> 00:57:36,160 CORRELATES WITH MAINTAINING GOOD 1287 00:57:36,160 --> 00:57:37,360 COGNITIVE FUNCTION AS PEOPLE 1288 00:57:37,360 --> 00:57:37,800 AGE. 1289 00:57:37,800 --> 00:57:43,440 AND WE HAVE RECENTLY SHOWN THAT 1290 00:57:43,440 --> 00:57:50,840 APO IS A MA A BA ALCOHOLICS IS D 1291 00:57:50,840 --> 00:57:52,480 WE HAVE DONE THE SAME FOR OTHER 1292 00:57:52,480 --> 00:57:52,920 OMICS. 1293 00:57:52,920 --> 00:57:56,880 SO WE ARE WORKING WITH THE 1294 00:57:56,880 --> 00:57:59,920 TRANSCRIPT TOMIC OF AGING AND 1295 00:57:59,920 --> 00:58:02,000 SAME THING WE HAVE LOOKED AT 1296 00:58:02,000 --> 00:58:06,520 PROTEOMICS OF AGING AND 1297 00:58:06,520 --> 00:58:07,800 LONGEVITY AND THE SAME TRAITS. 1298 00:58:07,800 --> 00:58:09,920 THE EMERGING PICTURE IS THERE 1299 00:58:09,920 --> 00:58:12,440 ARE MANY BIOMARKERS OF AGING. 1300 00:58:12,440 --> 00:58:22,200 THE TRANSCRIPT TOMB TRANCETOM IE 1301 00:58:22,200 --> 00:58:31,600 UNIQUE OMICS IN SEN SEN TEN ARD 1302 00:58:31,600 --> 00:58:33,040 WHAT THIS CAUSE AND EFFECT OF 1303 00:58:33,040 --> 00:58:36,040 LIVING TO EX EXTREME OLD AIMING. 1304 00:58:36,040 --> 00:58:37,280 WE HAVE MANY PIECES OF THE 1305 00:58:37,280 --> 00:58:38,960 PUZZLE BUT HONESTLY WE'RE FAR 1306 00:58:38,960 --> 00:58:42,760 FROM HAVING THE BIG MAUD ARE NOL 1307 00:58:42,760 --> 00:58:42,960 WORKING. 1308 00:58:42,960 --> 00:58:46,160 HOW DO WE CONNECT THESE DOTS? 1309 00:58:46,160 --> 00:58:47,560 NOW, WE HAVE BEEN WORKING FOR A 1310 00:58:47,560 --> 00:58:50,520 COUPLE OF YEARS ON USING VISION 1311 00:58:50,520 --> 00:58:53,240 NETWORKS FOR MODELING THE 1312 00:58:53,240 --> 00:58:57,040 COMPLEX SET OF INTERACTIONS 1313 00:58:57,040 --> 00:59:01,160 WITHIN GENETICS AND MULTI 1314 00:59:01,160 --> 00:59:04,880 PHENOTYPES IN OBSERVATIONAL 1315 00:59:04,880 --> 00:59:05,200 STUDIES. 1316 00:59:05,200 --> 00:59:14,840 SO BASBAYESIAN NETWORKS ARE MULI 1317 00:59:14,840 --> 00:59:17,560 VARIABLE AND UNVARIABLES AND 1318 00:59:17,560 --> 00:59:20,560 THESE RANDOM VARIABLES CAN 1319 00:59:20,560 --> 00:59:22,720 REPRESENT RISK FACTORS, 1320 00:59:22,720 --> 00:59:24,600 OUTCOMES, OMICS AND THE 1321 00:59:24,600 --> 00:59:27,720 ADVANTAGE OF BAYESIAN NETWORKS 1322 00:59:27,720 --> 00:59:30,840 IS COMPOSE A COMPLEX INTO 1323 00:59:30,840 --> 00:59:35,920 FACTORS BY LEVERAGING MARGINAL 1324 00:59:35,920 --> 00:59:38,160 INDEPENDENCE. 1325 00:59:38,160 --> 00:59:41,320 THIS MEANS WE HAVE A COMPLEX 1326 00:59:41,320 --> 00:59:42,960 MODEL THAT FACTORED INTO SMALL 1327 00:59:42,960 --> 00:59:48,960 MODEL AND 'S YEAR TO LEARN FROM 1328 00:59:48,960 --> 00:59:50,600 DATA AND BE USEFUL FROM 1329 00:59:50,600 --> 00:59:52,280 REASONING SO WHEN WE PUT THE 1330 00:59:52,280 --> 00:59:53,880 MODEL TOGETHER, WE CAN USE IT 1331 00:59:53,880 --> 00:59:57,480 FOR PREDICTING FROM PRESERVATION 1332 00:59:57,480 --> 00:59:59,440 OF THE NETWORK AND SOME OF THOSE 1333 00:59:59,440 --> 01:00:01,960 IN THE NETWORK WE CAN PREDICT 1334 01:00:01,960 --> 01:00:03,560 OUTCOMES AND WE CAN IDENTIFY 1335 01:00:03,560 --> 01:00:06,080 WHAT THE MOST LIKELY PATH TO 1336 01:00:06,080 --> 01:00:09,800 PARTICIPATE OUTCOMES, ET CETERA. 1337 01:00:09,800 --> 01:00:12,440 AND THERE ARE MANY VARIATIONS 1338 01:00:12,440 --> 01:00:16,880 FROM NETWORKS AND THAT I SHOULD 1339 01:00:16,880 --> 01:00:21,840 MENTION AND SOME OF MY 1340 01:00:21,840 --> 01:00:22,640 COLLABORATORS CALLED MACHINE 1341 01:00:22,640 --> 01:00:23,600 HEARING BECAUSE IN TERMS OF THE 1342 01:00:23,600 --> 01:00:26,680 ABILITY TO MODEL COMPLEX 1343 01:00:26,680 --> 01:00:28,080 SYSTEMS, THEY HAVE A LOT OF 1344 01:00:28,080 --> 01:00:28,400 ADVANTAGES. 1345 01:00:28,400 --> 01:00:31,680 WE CAN ALSO RELY ON AWARD FOR 1346 01:00:31,680 --> 01:00:33,160 LEANING STRUCTURE AND PARAMETER 1347 01:00:33,160 --> 01:00:36,880 OF NETWORKS AND ALSO FOR THE 1348 01:00:36,880 --> 01:00:37,960 DEVELOPMENT OF PROBABLE ALICE 1349 01:00:37,960 --> 01:00:48,560 TICK REASONING AND SOME ARE WE E 1350 01:00:55,400 --> 01:00:56,640 MODELS THAT CAN USE FOR STROKE 1351 01:00:56,640 --> 01:00:59,280 AND PATIENT WITH SICKLE CELL 1352 01:00:59,280 --> 01:01:01,400 ANEMIA AND SEVERITY OF THE 1353 01:01:01,400 --> 01:01:02,120 DISEASE, ET CETERA. 1354 01:01:02,120 --> 01:01:04,240 SO A LOT HAS BEEN DONE. 1355 01:01:04,240 --> 01:01:08,480 WHEN I LOOK AT THIS CARTOON 1356 01:01:08,480 --> 01:01:12,320 HERE, THIS WAS DONE IN 2005 AND 1357 01:01:12,320 --> 01:01:16,160 IF 2005, WORKING THE SET OF 250 1358 01:01:16,160 --> 01:01:17,000 WAS A BIG DEAL. 1359 01:01:17,000 --> 01:01:26,320 NOW WE TALK ABOUT 50 MILLION AND 1360 01:01:26,320 --> 01:01:27,600 THE OMICS DATA ARE REALLY 1361 01:01:27,600 --> 01:01:28,640 MASSIVE SO A LOT OF WORK NEEDS 1362 01:01:28,640 --> 01:01:32,640 TO BE DONE AND TO ADAPT TO MAKE 1363 01:01:32,640 --> 01:01:35,600 THEM FASTER AND BE VISIBLE AND 1364 01:01:35,600 --> 01:01:37,480 TO THE TASK WE HAVE AND IT'S 1365 01:01:37,480 --> 01:01:44,080 SOMETHING ELSE THAT I HAS BEEN 1366 01:01:44,080 --> 01:01:46,360 LOOKED AT GENERATING FOR AI AND 1367 01:01:46,360 --> 01:01:49,440 NOT SO MUCH AI FOR OBSERVATIONAL 1368 01:01:49,440 --> 01:01:51,800 DATA AND A LOT OF THE DATA WE 1369 01:01:51,800 --> 01:01:53,200 WORK IT ARE NOT RANDOM SAMPLES 1370 01:01:53,200 --> 01:01:55,320 SO WE WORKED WITH OBSERVATIONAL 1371 01:01:55,320 --> 01:01:56,560 STUDIES WHICH THEY'RE ON A 1372 01:01:56,560 --> 01:02:00,840 SPECIFIC STUDY DESIGN THAT HAS 1373 01:02:00,840 --> 01:02:08,440 BEEN USED AND WE HAVE LONG 1374 01:02:08,440 --> 01:02:09,080 STUDENT NAL CONVERSATION AND WE 1375 01:02:09,080 --> 01:02:10,000 ALWAYS HAVE MISSING DATA SO 1376 01:02:10,000 --> 01:02:16,760 THERE ARE A LOT OF CHALLENGES 1377 01:02:16,760 --> 01:02:20,440 THAT THEY ARE DESIGNED TO 1378 01:02:20,440 --> 01:02:26,600 OVERLOOK SOMEONE'S STRATEGIES 1379 01:02:26,600 --> 01:02:32,040 AND THERE'S A LOOK AT VARY A LOT 1380 01:02:32,040 --> 01:02:33,560 OF THE SOME OF THE OMICS 1381 01:02:33,560 --> 01:02:34,880 SUMMARIES WE WORK WITH. 1382 01:02:34,880 --> 01:02:37,000 IT'S A BIG CHALLENGE THAT WE 1383 01:02:37,000 --> 01:02:42,040 HAVE AND WE FEEL A LITTLE BIT IS 1384 01:02:42,040 --> 01:02:42,840 TO PUT TOGETHER CLOCKS OR SCORES 1385 01:02:42,840 --> 01:02:49,840 AND PLATFORM AND CAN BE USED SO 1386 01:02:49,840 --> 01:02:53,880 THE WORK NEEDS TO BE DONE TO 1387 01:02:53,880 --> 01:02:57,960 ADAPT THE SO I'LL GO THROUGH A 1388 01:02:57,960 --> 01:03:02,880 COUPLE OF EXAMPLES AND THE 1389 01:03:02,880 --> 01:03:05,240 WORKING WITH DATA WE NEED TO USE 1390 01:03:05,240 --> 01:03:07,040 SOME DATA REDUCTION TECHNIQUES 1391 01:03:07,040 --> 01:03:10,120 AND SO WE WORK WITH THEM SIMILAR 1392 01:03:10,120 --> 01:03:12,480 WITH THE REDUCTION THAT USE 1393 01:03:12,480 --> 01:03:15,880 CLOCKS AND NOT SO MUCH FOR THE 1394 01:03:15,880 --> 01:03:18,640 CLOCKS PER SE BUT TO BE ABLE TO 1395 01:03:18,640 --> 01:03:19,760 INCOMPETENT GREAT DATA AND THIS 1396 01:03:19,760 --> 01:03:21,960 SEEMS TO BE AN ADVANTAGEOUS 1397 01:03:21,960 --> 01:03:26,200 APPROACH COMPARED TO OTHER 1398 01:03:26,200 --> 01:03:28,400 REDUCTION 1399 01:03:28,400 --> 01:03:29,280 TECHNIQUES TO PRODUCE SOME THAT 1400 01:03:29,280 --> 01:03:32,640 ARE NOT EASY TO INTERPRET AND BY 1401 01:03:32,640 --> 01:03:36,160 ADAPTING THE WORKING GENETICS 1402 01:03:36,160 --> 01:03:38,360 THAT HAS BEEN VERY SUCCESSFUL 1403 01:03:38,360 --> 01:03:39,960 WITH THE DEVELOPMENT OF THE RISK 1404 01:03:39,960 --> 01:03:45,000 SCORE WE STARTED TO DEVELOP 1405 01:03:45,000 --> 01:03:50,040 OMICS SCORES SO IT'S VERY 1406 01:03:50,040 --> 01:03:54,560 MENTIONED INTRODUCED AND SCORES 1407 01:03:54,560 --> 01:03:57,280 AND I USED THE WORD SCORE 1408 01:03:57,280 --> 01:04:00,320 BECAUSE THESE ARE NOT REALLY 1409 01:04:00,320 --> 01:04:04,760 ONLY LINKED TO AGING BUT ANY 1410 01:04:04,760 --> 01:04:08,800 AGING TRAIT AND THIS IS VERY 1411 01:04:08,800 --> 01:04:10,560 HARD TO GET GENERATED RESULTS 1412 01:04:10,560 --> 01:04:12,720 WITH OUR PLATFORM INDEPENDENCE 1413 01:04:12,720 --> 01:04:18,320 OR STUDY INDEPENDENCE AND THERE 1414 01:04:18,320 --> 01:04:19,800 IS NEED FOR STANDARDS. 1415 01:04:19,800 --> 01:04:21,720 EVEN WITH THE LIMITATIONS IF WE 1416 01:04:21,720 --> 01:04:24,080 TAKE A VISION NETWORK ALGORITHM 1417 01:04:24,080 --> 01:04:25,880 WITH ALL THE DATA TOGETHER, WE 1418 01:04:25,880 --> 01:04:31,960 ENDS UP WITH THE NETWORK AND 1419 01:04:31,960 --> 01:04:34,720 THIS EXAMPLE IS AN EXAMPLE OF A 1420 01:04:34,720 --> 01:04:38,000 NETWORK AND WITH A LOT OF 1421 01:04:38,000 --> 01:04:39,680 CONNECTIONS IF WE START USING 1422 01:04:39,680 --> 01:04:41,600 SOME DATA SUMMARY TECHNIQUES WE 1423 01:04:41,600 --> 01:04:43,480 GET TO AN IMAGE THAT IS MUCH 1424 01:04:43,480 --> 01:04:44,920 MORE UNDERSTANDABLE AND IT'S 1425 01:04:44,920 --> 01:04:47,720 MORE INTUITIVE SO IF WE 1426 01:04:47,720 --> 01:04:50,280 SUMMARIZE SOME OF THE OMICS DATA 1427 01:04:50,280 --> 01:04:51,760 WITH MULTIPLE TRADES WE CLEAN UP 1428 01:04:51,760 --> 01:04:54,280 A LITTLE BIT THE PICTURE AND 1429 01:04:54,280 --> 01:04:56,680 THERE'S A LOT AND IT HAS TO BE 1430 01:04:56,680 --> 01:04:59,160 DONE AND A LOT OF THINKING. 1431 01:04:59,160 --> 01:05:03,840 WE NEED TO THINK MORE WAYS TO 1432 01:05:03,840 --> 01:05:05,280 SUMMARIZE THAT WE HAVE A LOT OF 1433 01:05:05,280 --> 01:05:06,320 PHENOTYPE ON INDIVIDUALING 1434 01:05:06,320 --> 01:05:10,800 INDIVIDUALS AND AS AN EXAMPLE, 1435 01:05:10,800 --> 01:05:12,200 FOR THOSE OF YOU INVOLVED IN 1436 01:05:12,200 --> 01:05:15,040 HUMAN STUDIES AND RELATED TO 1437 01:05:15,040 --> 01:05:17,080 COGNITION OR ALZHEIMER'S, WE 1438 01:05:17,080 --> 01:05:21,160 TYPICALLY ADMINISTER MANY, MANY 1439 01:05:21,160 --> 01:05:22,360 PSYCHOLOGICAL FOR PARTICIPANTS 1440 01:05:22,360 --> 01:05:25,280 AND THESE PSYCHOLOGICAL TESTS 1441 01:05:25,280 --> 01:05:27,920 ARE NOT INDEPENDENT THEY'RE 1442 01:05:27,920 --> 01:05:28,800 RELATED TO EACH AND THEY'RE 1443 01:05:28,800 --> 01:05:33,920 TRYING TO CAPTURE THOSE HIDDEN 1444 01:05:33,920 --> 01:05:36,040 STATES OF COGNITION THAT ARE NOT 1445 01:05:36,040 --> 01:05:37,440 EVIDENT AND THEY'RE NOT 1446 01:05:37,440 --> 01:05:38,560 MEASURABLE AND SO ONE OF THE 1447 01:05:38,560 --> 01:05:40,480 THINGS WE HAVE DONE WHICH IS 1448 01:05:40,480 --> 01:05:42,120 JUST ACCEPTED FOR PUBLICATION IN 1449 01:05:42,120 --> 01:05:43,440 THE JOURNAL OF ALZHEIMER'S 1450 01:05:43,440 --> 01:05:46,640 DISEASE IS TO USE A ANALYSIS TO 1451 01:05:46,640 --> 01:05:49,280 SEE WHETHER THERE ARE COGNITIVE 1452 01:05:49,280 --> 01:05:53,160 SIGNATURE THAT ARE BASED ON 1453 01:05:53,160 --> 01:05:55,960 TESTS AND CAN BE USED TO 1454 01:05:55,960 --> 01:05:57,720 INDIVIDUAL INTO THOSE WHO ARE 1455 01:05:57,720 --> 01:06:03,400 AGING BY MAINTAINING EXCELLENT 1456 01:06:03,400 --> 01:06:07,240 COGNITIVE FUNCTIONSEL MULTIPLE 1457 01:06:07,240 --> 01:06:08,160 DOMAINS AND WHILE OTHER 1458 01:06:08,160 --> 01:06:09,720 INDIVIDUALS HAVE GOOD MEMORIES 1459 01:06:09,720 --> 01:06:11,040 AND WITH OTHER COGNITIVE 1460 01:06:11,040 --> 01:06:13,280 FUNCTIONS AND IN TERMS OF THERE 1461 01:06:13,280 --> 01:06:15,200 ARE CLEAR FACTORS AND SOME OF 1462 01:06:15,200 --> 01:06:18,200 THE EXTREME HAVE RELATED TO 1463 01:06:18,200 --> 01:06:20,840 GENETICS SO TO HAVE A GOOD 1464 01:06:20,840 --> 01:06:23,320 GENETIC VARIANTS ASSOCIATED WITH 1465 01:06:23,320 --> 01:06:25,480 THE COGNITIVE PERFORMANCE, SEEMS 1466 01:06:25,480 --> 01:06:26,440 TO BE ASSOCIATED WITH THE 1467 01:06:26,440 --> 01:06:31,600 ABILITY TO MAINTAIN MULTI DOMAIN 1468 01:06:31,600 --> 01:06:34,640 GOOD COGNITIVE PERFORMANCE. 1469 01:06:34,640 --> 01:06:39,320 AND ANOTHER CHALLENGE THAT IS 1470 01:06:39,320 --> 01:06:41,360 BEING -- IT'S NOT BEEN ONE OF 1471 01:06:41,360 --> 01:06:42,440 THE CENTER PHONES IN MACHINE 1472 01:06:42,440 --> 01:06:44,200 LEANING IS THAT WHAT DO WE DO, 1473 01:06:44,200 --> 01:06:45,880 HOW DO WE LEARN THE NETWORKS 1474 01:06:45,880 --> 01:06:51,680 FROM CORRELATED DATA? 1475 01:06:51,680 --> 01:06:54,760 IN STUDIES OF LONGEVITY, MOST OF 1476 01:06:54,760 --> 01:06:58,560 OUR STUDIES INCLUDE THE RELATED 1477 01:06:58,560 --> 01:06:59,160 PEOPLE. 1478 01:06:59,160 --> 01:07:03,320 SO WE CAN'T REALLY IGNORE THE 1479 01:07:03,320 --> 01:07:04,000 RELATEDNESS ON INDIVIDUALS. 1480 01:07:04,000 --> 01:07:05,200 WE HAVE TO DO SOMETHING. 1481 01:07:05,200 --> 01:07:07,720 SO WE INTRODUCED THE MEDALS FOR 1482 01:07:07,720 --> 01:07:10,120 LEANING VISION NETWORKS FROM 1483 01:07:10,120 --> 01:07:13,040 RELATED INDIVIDUALS IN THE PAST 1484 01:07:13,040 --> 01:07:15,320 AND ONE OF THE CHALLENGES THIS 1485 01:07:15,320 --> 01:07:18,840 MANTLE CAN BE SPECIFICALLY SOUND 1486 01:07:18,840 --> 01:07:20,560 BUT COMPUTATIONALLY INEFFICIENT 1487 01:07:20,560 --> 01:07:25,720 SO WE'RE WORKING ON DEVELOPING 1488 01:07:25,720 --> 01:07:27,160 METHODS TO LEARN NETWORKS FROM 1489 01:07:27,160 --> 01:07:29,520 CLASSIC DATA BUT THESE ARE MAJOR 1490 01:07:29,520 --> 01:07:31,640 CHALLENGES IN COMPUTATIONAL 1491 01:07:31,640 --> 01:07:33,440 CHALLENGE AND IT IT'S A ROAD 1492 01:07:33,440 --> 01:07:34,760 BLOCK IF WE DEVELOP THESE 1493 01:07:34,760 --> 01:07:35,960 COMPLEX MODELS. 1494 01:07:35,960 --> 01:07:37,240 LOOKING AHEAD. 1495 01:07:37,240 --> 01:07:38,600 ONE OF THE BIG CHALLENGES WE 1496 01:07:38,600 --> 01:07:41,640 FACE IS THIS, WITH THE HUMAN 1497 01:07:41,640 --> 01:07:44,000 STUDIES, WE COLLECT GENETIC 1498 01:07:44,000 --> 01:07:47,200 MUTATION, WE CAN MEASURE 1499 01:07:47,200 --> 01:07:51,400 MOLECULAR DATA, AND EPIGENETIC 1500 01:07:51,400 --> 01:07:57,480 DATA, ET CETERA, AND WE TAKE A 1501 01:07:57,480 --> 01:08:01,800 SNAPSHOT OF ONE POINT AND TIME 1502 01:08:01,800 --> 01:08:03,440 AND WE HAVE A SYSTEM AND THE 1503 01:08:03,440 --> 01:08:04,640 SYSTEM IN WHICH THINGS CHANGE 1504 01:08:04,640 --> 01:08:06,760 AND CONSTANTLY CHANGE SO CHANGES 1505 01:08:06,760 --> 01:08:09,200 IN MOLECULAR THAT DETERMINE 1506 01:08:09,200 --> 01:08:10,560 OTHER CHANGES AND FEEDBACK 1507 01:08:10,560 --> 01:08:12,600 GROUPS. 1508 01:08:12,600 --> 01:08:14,920 SO, EVERYTHING IS COMPLICATED BY 1509 01:08:14,920 --> 01:08:17,760 THE EXPOSURE, LEFT THEM EXPOSURE 1510 01:08:17,760 --> 01:08:19,440 TO RISK FACTORS AND SO AS WE 1511 01:08:19,440 --> 01:08:21,240 COLLECT MORE AND MORE DATA, ONE 1512 01:08:21,240 --> 01:08:23,040 OF THE BIG CHALLENGES IS 1513 01:08:23,040 --> 01:08:24,880 SHIFTING INTO BUILDING DYNAMIC 1514 01:08:24,880 --> 01:08:27,400 MODELS WHICH IS ANOTHER LEVEL OF 1515 01:08:27,400 --> 01:08:37,920 REAL COMPLICATION AND AS AND AS 1516 01:08:58,240 --> 01:09:00,400 WAS MENTIONED AT THE BEGINNING, 1517 01:09:00,400 --> 01:09:04,760 WITH THE NEW POLICY AT THE NIH, 1518 01:09:04,760 --> 01:09:08,520 WE ARE THE STATUS OF GONG GIVE 1519 01:09:08,520 --> 01:09:10,000 TEE HAVE COMMIT TODAY SHARE DATA 1520 01:09:10,000 --> 01:09:11,760 WITH' LET PROGRAM AND IT'S PART 1521 01:09:11,760 --> 01:09:13,200 OF THE KNOWLEDGE PORTAL AND WE 1522 01:09:13,200 --> 01:09:14,640 ARE SUBMITTED DATA TO BE SHARED 1523 01:09:14,640 --> 01:09:17,120 BUT IN A COUPLE, IN I WOULD SAY 1524 01:09:17,120 --> 01:09:20,400 IN A FEW MONTHS, WE WILL START 1525 01:09:20,400 --> 01:09:21,600 POPULATING THIS PROGRAM WITH A 1526 01:09:21,600 --> 01:09:23,600 LOT OF STUDIES AND A LOT OF DATA 1527 01:09:23,600 --> 01:09:25,840 FROM LONGEVITY STUDIES. 1528 01:09:25,840 --> 01:09:28,120 SO THE DATA ARE NOT HERE YET AND 1529 01:09:28,120 --> 01:09:31,840 NOT ALL BUT IT WILL HAPPEN SOON. 1530 01:09:31,840 --> 01:09:33,280 SOMETHING THAT HOWEVER SUBPOENA 1531 01:09:33,280 --> 01:09:34,720 A CHALLENGE IS, THEY NEED TO 1532 01:09:34,720 --> 01:09:37,720 HAVE BENCHMARK DATA. 1533 01:09:37,720 --> 01:09:40,920 BENCHMARK DATA FOR EVALUATION SO 1534 01:09:40,920 --> 01:09:42,320 I DON'T KNOW THAT -- I DON'T 1535 01:09:42,320 --> 01:09:43,960 THINK I HAVE THE TIME HERE TO GO 1536 01:09:43,960 --> 01:09:45,320 THROUGH THIS BUT MAYBE I CAN USE 1537 01:09:45,320 --> 01:09:47,680 THE TIME OF THE DISCUSSION TO 1538 01:09:47,680 --> 01:09:49,920 TALK ABOUT OUR EXPERIENCE WITH 1539 01:09:49,920 --> 01:09:50,520 SYNTHETIC DATA. 1540 01:09:50,520 --> 01:09:52,280 SO THERE'S A GROWING INTEREST IN 1541 01:09:52,280 --> 01:09:55,480 GENERATING SYNTHETIC DATA THAT 1542 01:09:55,480 --> 01:09:58,200 ARE A STATISTICAL FAITHFUL 1543 01:09:58,200 --> 01:10:01,480 REPRESENTATION OF REAL DATA AND 1544 01:10:01,480 --> 01:10:03,560 IT CAN BE USED AS A BENCHMARK. 1545 01:10:03,560 --> 01:10:07,440 I'M GOING TO CONCLUDE HERE WITH 1546 01:10:07,440 --> 01:10:09,480 A LIST OF MY COLLABORATOR AND I 1547 01:10:09,480 --> 01:10:11,280 WANT TO EMPHASIZE THE STUDY WHO 1548 01:10:11,280 --> 01:10:13,280 WORK WITH US AND THE SUPPORT OF 1549 01:10:13,280 --> 01:10:17,320 THE ON GOING STUDIES AND THANK 1550 01:10:17,320 --> 01:10:20,000 YOU, VERY MUCH. 1551 01:10:20,000 --> 01:10:22,880 WE HAVE ONE MINUTE TO SPARE. 1552 01:10:22,880 --> 01:10:23,560 >>THANK YOU. 1553 01:10:23,560 --> 01:10:24,160 YES, IT'S GREAT. 1554 01:10:24,160 --> 01:10:27,400 THANK YOU, VERY MUCH. 1555 01:10:27,400 --> 01:10:29,040 I THINK WE ARE READY TO MOVE TO 1556 01:10:29,040 --> 01:10:32,480 THE FOURTH TALK, ALEXEY ARE YOU 1557 01:10:32,480 --> 01:10:32,760 READY? 1558 01:10:32,760 --> 01:10:33,040 >>YES. 1559 01:10:33,040 --> 01:10:36,920 >>SHARE YOUR SCREEN. 1560 01:10:36,920 --> 01:10:44,240 >>EVERYBODY SEE? 1561 01:10:44,240 --> 01:10:45,080 >>IT'S GREAT. 1562 01:10:45,080 --> 01:10:46,120 >>THANK YOU. 1563 01:10:46,120 --> 01:10:47,760 >>OKAY. 1564 01:10:47,760 --> 01:10:50,080 THANK YOU VERY MUCH FOR THE I AM 1565 01:10:50,080 --> 01:10:51,880 VATATION. 1566 01:10:51,880 --> 01:10:54,160 I APPRECIATE THE OPPORTUNITY TO 1567 01:10:54,160 --> 01:10:56,640 SHARE SOME RESENT DATA FROM THE 1568 01:10:56,640 --> 01:10:57,200 LAB. 1569 01:10:57,200 --> 01:10:59,560 SO, FOR THE NEXT 20 MINUTES OR 1570 01:10:59,560 --> 01:11:01,400 SO, I WOULD LIKE TO PRESENT A 1571 01:11:01,400 --> 01:11:02,600 APPROACH THAT WE HAVE BEEN 1572 01:11:02,600 --> 01:11:04,480 DEVELOPING FOR A NUMBER OF YEARS 1573 01:11:04,480 --> 01:11:06,840 NOW THAT IS BASED ON IMAGING AND 1574 01:11:06,840 --> 01:11:10,840 IN PARTICULAR IMAGING OF 1575 01:11:10,840 --> 01:11:11,440 EPIGENETIC INFORMATION IN THE 1576 01:11:11,440 --> 01:11:11,680 CELL. 1577 01:11:11,680 --> 01:11:13,320 SO MOST OF US WOULD BE ABLE TO 1578 01:11:13,320 --> 01:11:17,120 LOOK AT HUMAN FACE AND 1579 01:11:17,120 --> 01:11:18,840 APPROXIMATELY TELL AN AGE. 1580 01:11:18,840 --> 01:11:21,720 IT'S BASED ON SOME ASSESSMENTS 1581 01:11:21,720 --> 01:11:24,480 OF THE SKIN AND WHAT WE'RE 1582 01:11:24,480 --> 01:11:26,520 REALLY DOING IS QUICKLY 1583 01:11:26,520 --> 01:11:28,040 ASSESSING THE BIOLOGICAL AGE OF 1584 01:11:28,040 --> 01:11:29,800 A PERSON BASED ON A FACIAL 1585 01:11:29,800 --> 01:11:30,560 FEATURES. 1586 01:11:30,560 --> 01:11:33,600 SO, WHAT WE'RE TRYING TO SO IN 1587 01:11:33,600 --> 01:11:35,400 THE LAB IS DO SOMETHING SIMILAR 1588 01:11:35,400 --> 01:11:37,200 WITH CELLS AND THE QUESTION WAS, 1589 01:11:37,200 --> 01:11:39,440 CAN WE LOOK AT A CELL AND 1590 01:11:39,440 --> 01:11:42,560 PARTICULARLY IN THE EPIGENETIC 1591 01:11:42,560 --> 01:11:43,960 LANDSCAPE OF A CELL AND TELL HOW 1592 01:11:43,960 --> 01:11:46,600 OLD THE CELL IS. 1593 01:11:46,600 --> 01:11:48,120 SO, BY WAY OF INTRODUCTION, IT'S 1594 01:11:48,120 --> 01:11:51,280 I THINK COMMONLY WELL UNDERSTOOD 1595 01:11:51,280 --> 01:11:53,840 NOW THAT AGING IS A COMPLEX 1596 01:11:53,840 --> 01:11:56,400 PHENOMENON BUT A LOT OF THIS HAS 1597 01:11:56,400 --> 01:11:58,640 SOMETHING TO DO WITH EPIGENETIC. 1598 01:11:58,640 --> 01:12:00,200 BASICALLY THE SAME SET OF GENES 1599 01:12:00,200 --> 01:12:03,360 THAT ARE FAITHFULLY MAIN TAPED 1600 01:12:03,360 --> 01:12:06,000 TO FUNCTION EARLY IN LIFE NOW 1601 01:12:06,000 --> 01:12:07,360 ARE FAILING AND GIVEN SOME 1602 01:12:07,360 --> 01:12:09,240 NUMBER OF GENETIC MUTATIONS, BY 1603 01:12:09,240 --> 01:12:13,080 AND LARGE, I THINK THE APP' 1604 01:12:13,080 --> 01:12:15,880 GENETIC REGULATION IS FAGE WITH 1605 01:12:15,880 --> 01:12:18,160 AGE AND MEMBER OF PUBLICATIONS 1606 01:12:18,160 --> 01:12:20,000 ATTESTING FOR THIS RECENT PAPER, 1607 01:12:20,000 --> 01:12:21,880 HAS A LOT OF PUBLICITY, I 1608 01:12:21,880 --> 01:12:24,680 BELIEVE, SUGGESTING THAT THE 1609 01:12:24,680 --> 01:12:28,120 LOSS OF EPIGENETIC INFORMATION 1610 01:12:28,120 --> 01:12:29,920 IS THE CAUSE OF AGING. 1611 01:12:29,920 --> 01:12:33,560 THIS IS TO BRING HOME THE POINT 1612 01:12:33,560 --> 01:12:36,160 THAT IS REALLY FUNDAMENTAL FOR 1613 01:12:36,160 --> 01:12:38,360 THE TALK AND OUR APPROACH, 1614 01:12:38,360 --> 01:12:40,040 NAMELY THAT THE GLOBAL LANDSCAPE 1615 01:12:40,040 --> 01:12:42,520 OF EMMY AGAIN MODIFICATION, IF 1616 01:12:42,520 --> 01:12:45,360 APPROXIMATE YOU TAKE ALL THE 1617 01:12:45,360 --> 01:12:46,400 INFORMATION TOGETHER AND IMAGE 1618 01:12:46,400 --> 01:12:50,160 THEM IN 3D, CON FURS A STATE 1619 01:12:50,160 --> 01:12:52,240 WHICH IS ESSENTIAL TO IDENTITY 1620 01:12:52,240 --> 01:12:55,040 AND THAT IS A IDENTITY WE'LL TRY 1621 01:12:55,040 --> 01:12:57,640 TO IMAGE IN UNDERSTAND THAT THE 1622 01:12:57,640 --> 01:13:01,360 PROJECTORY WITH AGING. 1623 01:13:01,360 --> 01:13:04,560 SO, AS VERY IMPORTANT QUANTITY 1624 01:13:04,560 --> 01:13:06,600 TATING BIOLOGICAL FUNCTIONAL AGE 1625 01:13:06,600 --> 01:13:09,400 OF KEY IMPORTANCE, MUCH MORE 1626 01:13:09,400 --> 01:13:11,640 IMPORTANT THAN POTENTIALLY 1627 01:13:11,640 --> 01:13:13,200 KNOWING CHRONOLOGICAL AGE WHICH 1628 01:13:13,200 --> 01:13:15,600 DOES FOR US REALLY WELL AND A 1629 01:13:15,600 --> 01:13:17,080 NUMBER OF TOOLS AND APPROACHES 1630 01:13:17,080 --> 01:13:21,720 HAVE BEEN DEVELOPED WITH TIME 1631 01:13:21,720 --> 01:13:27,840 SUCH AS -- AND METH LAYING MARKS 1632 01:13:27,840 --> 01:13:31,600 AND MENTIONED SEVERAL TIMES. 1633 01:13:31,600 --> 01:13:36,320 DNA METHYLATION CLOCKS BUT IT 1634 01:13:36,320 --> 01:13:39,360 MIGHT HAVE LIMITATIONS TOO IN 1635 01:13:39,360 --> 01:13:40,360 PARTICULAR, WITH UNDERSTANDING 1636 01:13:40,360 --> 01:13:43,240 THE BIOLOGICAL DETERMINANTS AND 1637 01:13:43,240 --> 01:13:45,000 ALSO EXPANSIVE AND SOME 1638 01:13:45,000 --> 01:13:46,360 PRACTICAL ASPECT THAT COULD BE 1639 01:13:46,360 --> 01:13:48,000 IMPROVED. 1640 01:13:48,000 --> 01:13:50,400 SO, WE CAME UP WITH THE IDEA OF 1641 01:13:50,400 --> 01:13:55,240 IMAGING OF EPIGENETIC AGING AND 1642 01:13:55,240 --> 01:13:56,920 COINED THIS TERM AS AN APPROACH 1643 01:13:56,920 --> 01:13:59,080 OF IMAGING. 1644 01:13:59,080 --> 01:14:02,480 NOW, A COUPLE OF POINTS I'D LIKE 1645 01:14:02,480 --> 01:14:05,160 TO UNDERLINE HERE IS, WHICH I'LL 1646 01:14:05,160 --> 01:14:08,040 ADDRESS LATER DURING THE TALK, 1647 01:14:08,040 --> 01:14:11,160 BUT BASICALLY THAT IS APPROACHED 1648 01:14:11,160 --> 01:14:13,080 THAT ESSENTIALLY BASED ON 1649 01:14:13,080 --> 01:14:15,040 DETERMINING THE DISTANCE METRICS 1650 01:14:15,040 --> 01:14:16,160 BETWEEN THE INDIVIDUAL 1651 01:14:16,160 --> 01:14:18,240 MEASUREMENTS WITHOUT ANY PRIOR 1652 01:14:18,240 --> 01:14:20,480 ASSUMPTION OF CONNECTIVITY SUCH 1653 01:14:20,480 --> 01:14:23,120 AS AGING FOR EXAMPLE AND IT'S A 1654 01:14:23,120 --> 01:14:25,720 SINGLE CELL RESOLUTION BY DESIGN 1655 01:14:25,720 --> 01:14:30,640 AND THEN WE MOVE MORE IN 1656 01:14:30,640 --> 01:14:32,600 ANALYSIS AND SO THAT EXTRACTS 1657 01:14:32,600 --> 01:14:34,320 SOME ADDITIONAL INFORMATION 1658 01:14:34,320 --> 01:14:35,880 COMPARED TO THE APPAL SIS THAT 1659 01:14:35,880 --> 01:14:37,480 MOSTLY PRESENTED TODAY. 1660 01:14:37,480 --> 01:14:45,480 AND IT EMPLOYS ALL POSSIBLE 1661 01:14:45,480 --> 01:14:47,760 EPIGENETIC IT'S IN NATURE AND 1662 01:14:47,760 --> 01:14:50,560 LIMITED ONLY BY NUMBER OF COLORS 1663 01:14:50,560 --> 01:14:52,800 ORP WASHES YOU CAN DO IN 1664 01:14:52,800 --> 01:14:54,400 SIMULTANEOUSLY MEASURE AND ONE 1665 01:14:54,400 --> 01:14:56,160 THING THAT I HIGHLIGHTED HERE 1666 01:14:56,160 --> 01:14:57,720 WHICH I'M NOT GOING TO BE 1667 01:14:57,720 --> 01:15:00,240 ADDRESSING TODAY, IT'S A HOT 1668 01:15:00,240 --> 01:15:04,040 TOPIC IN THE LAB WE WORK ON BUT 1669 01:15:04,040 --> 01:15:05,920 IMAGELY IS UNIQUELY SUITABLE FOR 1670 01:15:05,920 --> 01:15:07,240 AGING WHICH IS HARD TO DO WITH 1671 01:15:07,240 --> 01:15:08,480 THE MOUSE CONVENTIONAL TECHNIQUE 1672 01:15:08,480 --> 01:15:10,640 AND AGAIN, THE POINT BROUGHT 1673 01:15:10,640 --> 01:15:11,920 BEFORE, IT'S QUITE COST 1674 01:15:11,920 --> 01:15:12,280 EFFECTIVE. 1675 01:15:12,280 --> 01:15:15,320 JUST TAKE AN IMAGE. 1676 01:15:15,320 --> 01:15:16,880 SO, HOW DO WE DO THIS? 1677 01:15:16,880 --> 01:15:19,480 WELL, WE'LL START WITH THE CELLS 1678 01:15:19,480 --> 01:15:21,000 AND MOST OF THE START IT WOULD 1679 01:15:21,000 --> 01:15:25,800 BE THE THICK CELLS STAINED WITH 1680 01:15:25,800 --> 01:15:31,120 CONVENTIONAL ANTIBODY SUCH AS 1681 01:15:31,120 --> 01:15:33,840 METHYLATION AND IT'S DONE ON A 1682 01:15:33,840 --> 01:15:36,600 INSTRUMENT AND FORMATS AND AFTER 1683 01:15:36,600 --> 01:15:39,640 WHICH WE EXTRACT FEATURES AND 1684 01:15:39,640 --> 01:15:41,520 CONVERT IMAGES INTO ESSENTIALLY 1685 01:15:41,520 --> 01:15:42,800 SERIES THE TABLES. 1686 01:15:42,800 --> 01:15:46,320 WE STARTED WITH USING 1687 01:15:46,320 --> 01:15:52,160 CONVENTIONAL FEATURES SUCH AS 1688 01:15:52,160 --> 01:15:53,120 METRICS AND EXTRA ADVERTISE 1689 01:15:53,120 --> 01:15:54,960 TICKS AND MOST OF THE WORK WILL 1690 01:15:54,960 --> 01:15:57,760 BE HERE PRESENTED FROM THOSE 1691 01:15:57,760 --> 01:16:00,200 FEATURES AND WE TALKED ABOUT 250 1692 01:16:00,200 --> 01:16:03,400 FEATURES PER CHANNEL OF IMAGING. 1693 01:16:03,400 --> 01:16:06,080 NOW, MORE RECENTLY WE ACTUALLY 1694 01:16:06,080 --> 01:16:11,120 DEVELOPED OUR OWN FEATURES BASED 1695 01:16:11,120 --> 01:16:14,200 ON PROBABILITY DIFFERENT 1696 01:16:14,200 --> 01:16:15,840 EPIGENETIC AND IT TAKES 1697 01:16:15,840 --> 01:16:19,560 ADVANTAGES OF THE IMAGING AND 1698 01:16:19,560 --> 01:16:20,000 COLOCALLIZATION. 1699 01:16:20,000 --> 01:16:21,560 SO THAT'S FOLLOWED BY 1700 01:16:21,560 --> 01:16:22,720 COMPUTATIONAL APPROACHES AND 1701 01:16:22,720 --> 01:16:23,920 DIFFERENT MACHINE LEANING 1702 01:16:23,920 --> 01:16:26,400 APPROACHES AND WE PUBLISHED HAD 1703 01:16:26,400 --> 01:16:27,400 NISH WOULD BE WHEN WE 1704 01:16:27,400 --> 01:16:29,560 DEMONSTRATED THE USEFULNESS OF 1705 01:16:29,560 --> 01:16:31,320 THIS APPROACH TO IDENTIFY 1706 01:16:31,320 --> 01:16:37,800 DIFFERENT CELL TYPES AND DRUG 1707 01:16:37,800 --> 01:16:38,520 SCREENING AND ET CETERA AND 1708 01:16:38,520 --> 01:16:45,440 THAT'S BEEN PUBLISHED A FEW 1709 01:16:45,440 --> 01:16:50,120 YEARS AGO AND THE COMPOUNDS AND 1710 01:16:50,120 --> 01:16:51,440 WE HAVE AYAR I'VE THAT MOST OF 1711 01:16:51,440 --> 01:16:55,120 THE DATA WAS PRESENTED RIGHT NOW 1712 01:16:55,120 --> 01:16:57,640 FOCUSING ON AGING. 1713 01:16:57,640 --> 01:17:00,760 SO, WE STARTED WITH PETER AS A 1714 01:17:00,760 --> 01:17:02,280 COLLABORATOR HERE AT INSTITUTE 1715 01:17:02,280 --> 01:17:05,240 AND LOOKING AT FOR EXAMPLE 1716 01:17:05,240 --> 01:17:06,200 SINGLE CELL IN THE BLOOD. 1717 01:17:06,200 --> 01:17:11,200 THIS IS AN EXAMPLE OF THE 1718 01:17:11,200 --> 01:17:13,560 MODULATION STEVE PAIKINING WHEN 1719 01:17:13,560 --> 01:17:15,640 WE LOOKED AT A YOUNGER MOUSE, AN 1720 01:17:15,640 --> 01:17:17,440 OLD MICE, TWO YOUNG AND TWO OLD 1721 01:17:17,440 --> 01:17:19,000 MICE, FOR EXAMPLE, AND ASK THE 1722 01:17:19,000 --> 01:17:20,400 QUESTION, CAN WE SEPARATE THEM 1723 01:17:20,400 --> 01:17:23,160 INTO SINGLE CELL LEVEL JUST BY 1724 01:17:23,160 --> 01:17:24,680 USING IMAGING. 1725 01:17:24,680 --> 01:17:26,880 SO THE PORTION THAT I MENTIONED 1726 01:17:26,880 --> 01:17:27,920 BEFORE, WAS USED. 1727 01:17:27,920 --> 01:17:29,360 WE IMAGED THE MARK AND 1728 01:17:29,360 --> 01:17:30,800 CONSTRUCTED THE FEATURES AND 1729 01:17:30,800 --> 01:17:36,200 THIS IS A SIMPLE ANALYSIS THAT 1730 01:17:36,200 --> 01:17:38,320 SUGGESTED THAT IN DEED YOUNG AND 1731 01:17:38,320 --> 01:17:39,960 OLD CELLS CAN BE SEPARATED. 1732 01:17:39,960 --> 01:17:42,480 WE USE ADDITIONAL CD3 MARK TO 1733 01:17:42,480 --> 01:17:52,600 FOCUS ON T CELLS ANDED TO AVOID 1734 01:17:52,600 --> 01:17:53,760 CELL WITH AGE. 1735 01:17:53,760 --> 01:17:57,040 ON THE SINGLE CELL YOU CAN SEE 1736 01:17:57,040 --> 01:17:59,960 VISUALLY YOU CAN CELL WILL BE 1737 01:17:59,960 --> 01:18:01,080 SEPARATED AND AGAIN IT SUGGESTS 1738 01:18:01,080 --> 01:18:06,000 A REALLY GOOD SEPARATION. 1739 01:18:06,000 --> 01:18:07,680 WE THEN FOLLOW THAT WITH 1740 01:18:07,680 --> 01:18:12,480 EXPERIMENT WHEN WE ISOLATE IT SO 1741 01:18:12,480 --> 01:18:14,840 SITES FROM SEVERAL YOUNG AND OLD 1742 01:18:14,840 --> 01:18:20,280 MICE FIVE AND 20 MONTHS OLD MICE 1743 01:18:20,280 --> 01:18:22,640 AND THIS WAS IMAGE WITH A COUPLE 1744 01:18:22,640 --> 01:18:26,040 OF MARKS PRESENTED HERE AND SO, 1745 01:18:26,040 --> 01:18:28,960 WE PRESENTED THEM IN THIS 1746 01:18:28,960 --> 01:18:31,200 DIAGRAM WHERE WE ESSENTIALLY 1747 01:18:31,200 --> 01:18:34,080 MEASURED THE DISTANCE FOR EACH 1748 01:18:34,080 --> 01:18:36,320 CELL, WE MEASURED FROM THE OLD 1749 01:18:36,320 --> 01:18:38,320 AND DISTANCE FROM THE YOUNG 1750 01:18:38,320 --> 01:18:39,320 CELLS. 1751 01:18:39,320 --> 01:18:41,080 AND NOW EACH DOT HERE NOW 1752 01:18:41,080 --> 01:18:47,120 INDICATED IS A MOUSE AND WE 1753 01:18:47,120 --> 01:18:48,560 CONDUCTED THISSER PERMENT THREE 1754 01:18:48,560 --> 01:18:52,040 TIMES TO SEE HOW STABLE AND 1755 01:18:52,040 --> 01:18:52,920 REPRODUCE ABLE. 1756 01:18:52,920 --> 01:18:55,400 THE YOUNG ANIMAL AND OLD ANIMAL 1757 01:18:55,400 --> 01:19:00,560 ARE CLUSTERED IN THE 1758 01:19:00,560 --> 01:19:02,240 CORRESPONDING CONNERS SUGGESTING 1759 01:19:02,240 --> 01:19:06,280 THEY'RE ENOUGH TO SEPARATE YOUNG 1760 01:19:06,280 --> 01:19:12,000 AND OLD CELLS BY IMAGING. 1761 01:19:12,000 --> 01:19:14,960 NOW, FALLING ON THAT, WE LOOKED 1762 01:19:14,960 --> 01:19:17,880 AT A COLLECTION OF CELLS 1763 01:19:17,880 --> 01:19:22,600 ISOLATED FROM MICE, IN 1764 01:19:22,600 --> 01:19:25,440 PARTICULAR THEY CD3 SUBSET 1765 01:19:25,440 --> 01:19:28,880 MODULATED FROM MICE SPAN 1766 01:19:28,880 --> 01:19:30,200 INTERESTED 53 DAYS TO 68 DAYS 1767 01:19:30,200 --> 01:19:32,120 AND WE DID THE SAME PLOT AND THE 1768 01:19:32,120 --> 01:19:34,880 SAME APPROACH AND WE ESSENTIALLY 1769 01:19:34,880 --> 01:19:39,520 PLOT EVERYTHING SEPARATED BY A 1770 01:19:39,520 --> 01:19:41,160 DISTANCE FROM THE YOUNG AND OLD 1771 01:19:41,160 --> 01:19:42,920 AND EACH DOT IS A REPLICA AND 1772 01:19:42,920 --> 01:19:45,080 THERE'S A COUPLE OF MICE PER 1773 01:19:45,080 --> 01:19:46,600 TIME POINT AND A NUMBER OF REP 1774 01:19:46,600 --> 01:19:50,160 REPLICAS. 1775 01:19:50,160 --> 01:19:52,800 YOU CAN SEE THAT THERE SEEMS TO 1776 01:19:52,800 --> 01:19:55,040 FALL ON THIS LINE THAT CONNECTS 1777 01:19:55,040 --> 01:20:02,680 YOUNG AND OLD MICE. 1778 01:20:02,680 --> 01:20:06,920 SO, IF YOU PROJECT THE DATA ON 1779 01:20:06,920 --> 01:20:10,000 THAT AXIS IT'S THE LOWER PART 1780 01:20:10,000 --> 01:20:17,640 WHERE THIS EPIGENETIC AXIS WITH 1781 01:20:17,640 --> 01:20:19,760 THE MICE PROGRESS ALONG THIS 1782 01:20:19,760 --> 01:20:21,920 EPIGENETIC AXIS AND THE DISTANCE 1783 01:20:21,920 --> 01:20:26,000 IS THE COMPONENT THAT IS TO THE 1784 01:20:26,000 --> 01:20:26,680 AXIS. 1785 01:20:26,680 --> 01:20:28,280 SO, WE ASKED THE QUESTION, WILL 1786 01:20:28,280 --> 01:20:30,480 THAT PROGRESSION ALONG THAT AXIS 1787 01:20:30,480 --> 01:20:32,240 CORRELATE WITH AGE AND THAT'S A 1788 01:20:32,240 --> 01:20:34,840 SIMPLE CORRELATION THAT WE HAVE 1789 01:20:34,840 --> 01:20:38,600 HERE BOTH FOR THE PERIL RAL 1790 01:20:38,600 --> 01:20:41,600 BLOOD AND ALL THE CD3 POSITIVE 1791 01:20:41,600 --> 01:20:43,320 COM PART OF THIS. 1792 01:20:43,320 --> 01:20:44,640 IT'S IMPORTANT TO BRING THAT 1793 01:20:44,640 --> 01:20:50,120 THIS IS REALLY NARROW AND 1794 01:20:50,120 --> 01:20:51,520 REGRESSION OR ANY OTHER CHANGED 1795 01:20:51,520 --> 01:20:51,920 OF THE DATA. 1796 01:20:51,920 --> 01:20:54,280 THIS IS SIMPLY PLOTTING ONE SET 1797 01:20:54,280 --> 01:20:56,120 AGAINST THE OTHER DATASET SORT 1798 01:20:56,120 --> 01:20:57,160 OF AS IT IS. 1799 01:20:57,160 --> 01:20:59,360 THE IMAGING VERSUS CHRONOLOGICAL 1800 01:20:59,360 --> 01:21:00,880 AGENT AND YOU SAID IT EMERGES 1801 01:21:00,880 --> 01:21:04,560 AND IT'S NOT THE SUPER STRONG 1802 01:21:04,560 --> 01:21:06,080 IT'S DECENT AND DEFINITELY 1803 01:21:06,080 --> 01:21:07,360 SIGNIFICANT. 1804 01:21:07,360 --> 01:21:09,400 SO, YOU MAY THINK THAT THIS IS 1805 01:21:09,400 --> 01:21:11,440 SORT OF A APPROACH TO ANALYZING 1806 01:21:11,440 --> 01:21:15,280 THE AGING OR PROGRESSION ALONG 1807 01:21:15,280 --> 01:21:16,400 EPIGENETIC AGING SO WE TURNED 1808 01:21:16,400 --> 01:21:17,920 THE APPROACHES OR TERMINAL 1809 01:21:17,920 --> 01:21:19,080 APPROACHES TO LOOK AT THIS 1810 01:21:19,080 --> 01:21:19,920 QUESTION. 1811 01:21:19,920 --> 01:21:22,800 SO, FIRST WE JUST USE THE 1812 01:21:22,800 --> 01:21:26,160 REGULAR PC ANALYSIS AND PLOTTED 1813 01:21:26,160 --> 01:21:27,080 THE SIGNATURES ALONG THE COM 1814 01:21:27,080 --> 01:21:28,040 POPE ANT. 1815 01:21:28,040 --> 01:21:30,880 AND YOU CAN APPRECIATE THAT THE 1816 01:21:30,880 --> 01:21:34,120 PC1 COM PHONE SEPARATES THE CELL 1817 01:21:34,120 --> 01:21:35,880 TYPES BY THE NEGATIVE AND 1818 01:21:35,880 --> 01:21:37,800 POSITIVE WHERE THE COMPONENT 1819 01:21:37,800 --> 01:21:40,840 REALLY EXTRACTS THE AGING AXIS 1820 01:21:40,840 --> 01:21:42,040 FROM THE DATA. 1821 01:21:42,040 --> 01:21:44,200 VERY SIMILAR TO WHAT YOU HAVE 1822 01:21:44,200 --> 01:21:46,520 JUST SEEN BEFORE WITH THE 1823 01:21:46,520 --> 01:21:48,160 EPIGENETIC AGE AXIS 1824 01:21:48,160 --> 01:21:49,480 CONSTRUCTION. 1825 01:21:49,480 --> 01:21:53,800 FURTHER, WE COLLABORATE WITH THE 1826 01:21:53,800 --> 01:21:55,160 COLLEAGUE AND COLLATE RATE OR 1827 01:21:55,160 --> 01:21:57,880 AND USED THE HYPERBOLIC SPACE 1828 01:21:57,880 --> 01:21:59,760 WHICH IS VERY INTERESTING SPACE 1829 01:21:59,760 --> 01:22:03,400 AND I USE IT LATER AND I TALKED 1830 01:22:03,400 --> 01:22:06,800 TO APP EMERGENCE EMBEDDING WHICH 1831 01:22:06,800 --> 01:22:08,840 CAN HANDLE MUCH BETTER 1832 01:22:08,840 --> 01:22:11,120 DEMENTIONALITY THAT COULD BE 1833 01:22:11,120 --> 01:22:13,960 PROBLEMATIC AND IN SPACE AND 1834 01:22:13,960 --> 01:22:16,520 SUITABLE FOR THE ORGANIZED 1835 01:22:16,520 --> 01:22:19,040 BIOLOGICAL DATA AND YOU WILL SEE 1836 01:22:19,040 --> 01:22:22,160 IN SECONDLY IT'S A OF STATE OF 1837 01:22:22,160 --> 01:22:24,920 EXPANSE AND THE CONNECTION 1838 01:22:24,920 --> 01:22:26,840 BETWEEN THE TWO DOTS AND SPACE 1839 01:22:26,840 --> 01:22:30,880 NOT LOOK TO POSITIONS AND NO 1840 01:22:30,880 --> 01:22:33,160 MORE LINEAR STRAIGHT LINE WITH 1841 01:22:33,160 --> 01:22:33,800 THIS LINE. 1842 01:22:33,800 --> 01:22:38,760 SO WE PROJECTED BOTH CD3 AND 1843 01:22:38,760 --> 01:22:42,600 POSITIVE AND NEGATIVE STYLES OR 1844 01:22:42,600 --> 01:22:45,600 AGE LABELED STYLES IN THE 1845 01:22:45,600 --> 01:22:47,000 HYPERBOLIC SPACE AND WE RECEIVED 1846 01:22:47,000 --> 01:22:53,480 IT IN A SIMPLE OF THE EPIGENETIC 1847 01:22:53,480 --> 01:22:53,960 TRAJECTORY WITH AIMING. 1848 01:22:53,960 --> 01:22:56,880 I GUESS THIS IS SORT OF WHAT IS 1849 01:22:56,880 --> 01:23:02,040 IS CONVINCING TO US TO US THAT 1850 01:23:02,040 --> 01:23:04,680 IMAGING OF THE LANDSCAPE IN THE 1851 01:23:04,680 --> 01:23:06,600 CELLS RESULTED IN THIS EMERGENCE 1852 01:23:06,600 --> 01:23:11,600 OF THE TRAJECTORY WITHOUT ANY 1853 01:23:11,600 --> 01:23:13,440 REGRESSION OR ANY OTHER 1854 01:23:13,440 --> 01:23:14,520 MATHEMATICAL RATHER THAN JUST 1855 01:23:14,520 --> 01:23:18,400 PLOTTING AND EMBEDDING THEM IN 1856 01:23:18,400 --> 01:23:20,640 THE PC ANALYSIS INCLUDING SPACE 1857 01:23:20,640 --> 01:23:22,080 OR HYPERBOLIC SPACE. 1858 01:23:22,080 --> 01:23:25,360 SO THIS TRAJECTORY IS PRESENT IN 1859 01:23:25,360 --> 01:23:26,560 THE CELLS. 1860 01:23:26,560 --> 01:23:29,480 WE ALSO LOOKED AT DIFFERENT 1861 01:23:29,480 --> 01:23:31,880 SOLID ORGANS AND THAT'S AN 1862 01:23:31,880 --> 01:23:33,280 EXAMPLE OF THE FIBER ORGANS THAT 1863 01:23:33,280 --> 01:23:38,800 WE ANALYZED, SUBSTANTIALLY LESS 1864 01:23:38,800 --> 01:23:42,320 AGE GROUPS, THIS IS 15 AND 20 1865 01:23:42,320 --> 01:23:44,200 SOMETHING MONTHS AND WE SAW THE 1866 01:23:44,200 --> 01:23:46,280 PROGRESSION AND EMERGENCE OF 1867 01:23:46,280 --> 01:23:48,000 THIS TRAJECTORY IN THE SOLID 1868 01:23:48,000 --> 01:23:49,960 ORGANS WITH AN INTERESTING 1869 01:23:49,960 --> 01:23:52,000 COUPLE OF VEINERS AND IT WAS 1870 01:23:52,000 --> 01:23:57,000 KNOWN THAT BRAIN HAS THE LOWER, 1871 01:23:57,000 --> 01:24:00,560 SLOWER AGE ACCELERATION JUDGED 1872 01:24:00,560 --> 01:24:03,120 BY THE CLOCK AND ORGAN LIVING 1873 01:24:03,120 --> 01:24:04,800 AND IT WOULD SHOW THAT SO WE 1874 01:24:04,800 --> 01:24:06,400 ALSO OBSERVED THAT PROGRESSION 1875 01:24:06,400 --> 01:24:10,720 OF THE BRAIN IS SLOWER COMPARED 1876 01:24:10,720 --> 01:24:13,760 TO OTHER ANALYZED AND ALSO, 1877 01:24:13,760 --> 01:24:17,280 SORRY ABOUT THIS, AND ALSO WE 1878 01:24:17,280 --> 01:24:21,160 LOOKED AT CORRELATIONS BECAUSE 1879 01:24:21,160 --> 01:24:22,600 ALL THESE ORGANS WERE EXTRACTED 1880 01:24:22,600 --> 01:24:24,640 FROM THE SAME ANIMALS SO WE WERE 1881 01:24:24,640 --> 01:24:27,520 ABLE TO ASK THE QUESTION WERE 1882 01:24:27,520 --> 01:24:29,320 SHE'S OF THESE ORGANS AGE KIND 1883 01:24:29,320 --> 01:24:31,920 OF IN THE CORRELATED FASHION AND 1884 01:24:31,920 --> 01:24:33,840 FOR THE BRAIN AND HEART BUT NOT 1885 01:24:33,840 --> 01:24:36,200 OTHER ORGANS AND IT'S 1886 01:24:36,200 --> 01:24:37,400 INTERESTING BECAUSE THERE'S SOME 1887 01:24:37,400 --> 01:24:41,160 INDICATION IN DEED THAT BRAIN EX 1888 01:24:41,160 --> 01:24:44,200 HEART CAN HAVE A SIMILAR 1889 01:24:44,200 --> 01:24:45,480 MOLECULAR PATHWAY IN PARTICULAR 1890 01:24:45,480 --> 01:24:47,560 AND INDEXES ASSOCIATED WITH THE 1891 01:24:47,560 --> 01:24:50,880 BRAIN AND AGING AND HEART STUDY 1892 01:24:50,880 --> 01:24:55,320 RECENTLY. 1893 01:24:55,320 --> 01:24:58,800 SO, THERE WAS A DESCRIPTIVE APP 1894 01:24:58,800 --> 01:25:00,280 ALF AGE AND WE ASKED WHETHER THE 1895 01:25:00,280 --> 01:25:08,000 AGE DEFINED BY IMAGING WOULD 1896 01:25:08,000 --> 01:25:10,360 CORRELATE WITH THE FUNCTIONSAL 1897 01:25:10,360 --> 01:25:13,200 KNOWN TO EFFECT HEALTH AND SO WE 1898 01:25:13,200 --> 01:25:17,480 LOOK AT TWO THINGS, WHICH IS THE 1899 01:25:17,480 --> 01:25:19,120 THERAPY TREATMENT WHICH IS KNOWN 1900 01:25:19,120 --> 01:25:22,360 TO ACCELERATE AGING AND AGAIN WE 1901 01:25:22,360 --> 01:25:25,040 COMPARE IT HERE CHRONOLOGICAL 1902 01:25:25,040 --> 01:25:28,840 IDENTICAL MICE TREATED FOR THREE 1903 01:25:28,840 --> 01:25:33,320 MONTHS AND SIMILAR TO THE 1904 01:25:33,320 --> 01:25:35,240 PUBLISHED SYSTEMIC AND SINGLE 1905 01:25:35,240 --> 01:25:37,960 DOSE AND THEN WE LOOK AT TWO 1906 01:25:37,960 --> 01:25:41,920 MONTHS, TWO WEEKS LATER, IN 1907 01:25:41,920 --> 01:25:45,920 ISOLATED AND WE OBSERVED THAT 1908 01:25:45,920 --> 01:25:48,200 THE DOCS TREATED MICE HAVE ALL 1909 01:25:48,200 --> 01:25:49,920 THE SIGNATURE COMPARED TO 1910 01:25:49,920 --> 01:25:55,040 UNTREATED MICE IN AGE CONTROL. 1911 01:25:55,040 --> 01:25:58,640 WITH ANDERSON WE ASKED CALORIC 1912 01:25:58,640 --> 01:25:59,720 RESTRICTION WOULD RESULT IN THE 1913 01:25:59,720 --> 01:26:05,200 SLOWING DOWN OF EPIGENETIC 1914 01:26:05,200 --> 01:26:12,000 SIGNATURES AND SO WE GOT SAMPLES 1915 01:26:12,000 --> 01:26:13,560 WITH ROWS A LYNN AND OBSERVED 1916 01:26:13,560 --> 01:26:14,280 THAT CHANGE. 1917 01:26:14,280 --> 01:26:19,040 WE WANT TO ASK WHETHER IT 1918 01:26:19,040 --> 01:26:19,600 CORRELATES WITH INDIVIDUAL 1919 01:26:19,600 --> 01:26:21,720 FUNCTION BECAUSE WE'RE LOOKING 1920 01:26:21,720 --> 01:26:22,720 AT INDIVIDUAL SIGNATURES SO WE 1921 01:26:22,720 --> 01:26:26,760 DID EXPERIMENT WITH AMANDA 1922 01:26:26,760 --> 01:26:30,960 ROBERTS WHERE WE LOOKED AT THE 1923 01:26:30,960 --> 01:26:35,000 CHRONOLOGICAL IDENTICAL MICE AND 1924 01:26:35,000 --> 01:26:36,000 20 MICE AND WENT THROUGH A 1925 01:26:36,000 --> 01:26:39,840 NUMBER OF BEHAVIOR METABOLIC 1926 01:26:39,840 --> 01:26:42,600 TESTS AND MEASURED THE LANDSCAPE 1927 01:26:42,600 --> 01:26:43,840 AND SKELETAL MUSCLE AND ASKED 1928 01:26:43,840 --> 01:26:47,040 THE QUESTION, CAN WE ANALYZE THE 1929 01:26:47,040 --> 01:26:48,880 BEHAVIOR AND CORRELATE BEHAVIOR 1930 01:26:48,880 --> 01:26:52,000 OF THESE MICE WITH THEIR 1931 01:26:52,000 --> 01:26:59,320 EPIGENETIC SIGNATURES SO THE 1932 01:26:59,320 --> 01:27:00,880 TRAJECTORY OF CORRELATE WITH 1933 01:27:00,880 --> 01:27:03,440 READOUTS AND WE OBSERVED IN NINE 1934 01:27:03,440 --> 01:27:06,400 CLUSTERS OF THESE ORGANS IN SO 1935 01:27:06,400 --> 01:27:10,520 IT'S VERY INTERESTING THAT THEY 1936 01:27:10,520 --> 01:27:14,160 REALLY REFLECT OF THE LOCO MOTOR 1937 01:27:14,160 --> 01:27:15,680 AND METABOLIC FIX. 1938 01:27:15,680 --> 01:27:21,640 YOU CAN SEE AVERAGE RAILING WITH 1939 01:27:21,640 --> 01:27:23,360 SHIFT OR PAR PARTICIPATE TO THE 1940 01:27:23,360 --> 01:27:29,920 SIGNATURES FOR THE YOUNGESTEST G 1941 01:27:29,920 --> 01:27:30,840 YOUNGEST AND THE SAME WILL 1942 01:27:30,840 --> 01:27:33,560 PARTICIPATE WITH THE OPPOSITE 1943 01:27:33,560 --> 01:27:37,320 WITH OLDER STATES SO WE THINK 1944 01:27:37,320 --> 01:27:39,840 THAT IT CORRELATES WITH 1945 01:27:39,840 --> 01:27:42,400 INDIVIDUAL ORGANIZE APP AND 1946 01:27:42,400 --> 01:27:43,600 METABOLIC READOUTS AND WORKING 1947 01:27:43,600 --> 01:27:45,400 OUT THE PREDICTION POSSIBILITIES 1948 01:27:45,400 --> 01:27:47,560 AND THE LAST THING I WANT TO 1949 01:27:47,560 --> 01:27:50,680 QUICKLY GO OVER IS HETEROGENEITY 1950 01:27:50,680 --> 01:27:52,720 AND SO BECAUSE WE'RE IMAGING A 1951 01:27:52,720 --> 01:27:56,280 NUMBER OF CELLS, WE CAN NOW OF 1952 01:27:56,280 --> 01:27:57,600 ADDRESS ORIGINAL A TEE BETWEEN 1953 01:27:57,600 --> 01:28:00,760 INDIVIDUALS CELLS. 1954 01:28:00,760 --> 01:28:02,440 USING THE VARIANTS AND WHAT WE 1955 01:28:02,440 --> 01:28:11,080 FOUND IS IS HIT TREMENDOUS HETEE 1956 01:28:11,080 --> 01:28:13,800 CAN SPLIT THIS BY MARK AND CELL 1957 01:28:13,800 --> 01:28:18,840 TYPES AND WE OBSERVED THAT THE 1958 01:28:18,840 --> 01:28:20,680 HETEROGENEITY AND COMPONENT AND 1959 01:28:20,680 --> 01:28:23,160 IT'S MORE STABLE AND BECAUSE OF 1960 01:28:23,160 --> 01:28:26,800 THE HYPERBOLIC FUNCTION HAS IT 1961 01:28:26,800 --> 01:28:30,080 CAN PREDICT THE MAXIMUM LIFESPAN 1962 01:28:30,080 --> 01:28:33,600 LIMIT FOR MICE BASED ON, FOR 1963 01:28:33,600 --> 01:28:34,480 EXAMPLE, CD3 POSITIVE CELLS 1964 01:28:34,480 --> 01:28:36,520 WHICH IS INTERESTINGLY BETWEEN 1965 01:28:36,520 --> 01:28:39,920 THE MAXIMUM LIFESPAN IN THE LAB 1966 01:28:39,920 --> 01:28:42,840 AND OBSERVED IN THE WILD TYPE 1967 01:28:42,840 --> 01:28:43,440 MOUSE. 1968 01:28:43,440 --> 01:28:48,240 SO, IT MAKES IT VERY REASONABLE 1969 01:28:48,240 --> 01:28:55,280 I THINK SO I WANT TO THINK ABOUT 1970 01:28:55,280 --> 01:29:00,080 IT AND THE HETEROGENEITY AS A 1971 01:29:00,080 --> 01:29:03,040 REALLY TRAVELING THROUGH TIME 1972 01:29:03,040 --> 01:29:07,240 AND SPACE WHERE ALONG THAT 1973 01:29:07,240 --> 01:29:08,760 TRAJECTORIES, FOR EXAMPLE, IT'S 1974 01:29:08,760 --> 01:29:10,600 TWO DIFFERENT ORGANS AND 1975 01:29:10,600 --> 01:29:12,720 ORGANISMS AND THE RETRO GENEITY 1976 01:29:12,720 --> 01:29:16,400 INCREASE WITH AGE AND WITH THE 1977 01:29:16,400 --> 01:29:18,040 CELLS AND UNTIL IT REACHES THE 1978 01:29:18,040 --> 01:29:21,160 MAXIMUM POSSIBLE VARIANTS AND 1979 01:29:21,160 --> 01:29:22,120 COMPARABLE WITH LIFE AND THEN 1980 01:29:22,120 --> 01:29:24,120 THIS VARIANCE COULD BE AT A 1981 01:29:24,120 --> 01:29:26,120 DIFFERENT TIME IN THE TRAJECTORY 1982 01:29:26,120 --> 01:29:27,120 AND IN DIFFERENT INDIVIDUALS AND 1983 01:29:27,120 --> 01:29:31,080 THAT IS HOW OF WE TRIED TO 1984 01:29:31,080 --> 01:29:33,240 RECONCILE THOSE AGE TRAJECTORIES 1985 01:29:33,240 --> 01:29:37,960 AND INCREASE THE CHROMATIN 1986 01:29:37,960 --> 01:29:38,520 HETEROGENEITY. 1987 01:29:38,520 --> 01:29:43,440 SO TO SUM IT UP, THE FINAL 1988 01:29:43,440 --> 01:29:49,160 POINTS, SO EXISTENCE OF THIS 1989 01:29:49,160 --> 01:29:51,920 EPIGENETIC THAT CAN REVEAL BY 1990 01:29:51,920 --> 01:29:59,920 IMAGING THAT EP GENETIC AGE WITH 1991 01:29:59,920 --> 01:30:03,920 A LIFESPAN AND WE SHOW THAT 1992 01:30:03,920 --> 01:30:04,760 INDIVIDUAL EPIGENETIC FEATURES 1993 01:30:04,760 --> 01:30:07,920 AND SKELETAL MUSCLE OF THE 1994 01:30:07,920 --> 01:30:12,040 IDENTICAL MICE CORRELATE WITH 1995 01:30:12,040 --> 01:30:13,840 ORGANISMAL AND IT'S VERY 1996 01:30:13,840 --> 01:30:19,160 INTERESTING IN A ZAR CANYON 1997 01:30:19,160 --> 01:30:21,400 INDEPENDENT WAY AND THE INCREASE 1998 01:30:21,400 --> 01:30:23,920 WITH AGE AND PROVIDING AN 1999 01:30:23,920 --> 01:30:24,840 ESTIMATED OF THE SPY LAN AND I 2000 01:30:24,840 --> 01:30:27,680 DID MENTION WE ARE WORKING ON 2001 01:30:27,680 --> 01:30:31,160 LIFE IMAGING OF EPIGENETIC 2002 01:30:31,160 --> 01:30:31,760 LANDSCAPE. 2003 01:30:31,760 --> 01:30:34,000 I'M VERY FORTUNATE TO HAVE A 2004 01:30:34,000 --> 01:30:34,960 TALENTED GROUP OF INDIVIDUALS 2005 01:30:34,960 --> 01:30:37,200 WORKING WITH ME IN THE LAB AND 2006 01:30:37,200 --> 01:30:43,160 IT'S A COLLABORATION WITH MY 2007 01:30:43,160 --> 01:30:47,960 COLLEAGUE. 2008 01:30:47,960 --> 01:30:49,960 AND SCRIPTS, AND THANK YOU FOR 2009 01:30:49,960 --> 01:30:51,720 NATIONAL AGING FOR FUNDING 2010 01:30:51,720 --> 01:30:55,800 SUPPORTING THIS WORK. 2011 01:30:55,800 --> 01:30:58,840 >>THANK YOU. 2012 01:30:58,840 --> 01:31:02,000 SO, THIS CONCLUDES THE 2013 01:31:02,000 --> 01:31:05,720 PRESENTATION PART OF THE SESSION 2014 01:31:05,720 --> 01:31:08,600 AND NOW WE HAVE WHAT IS IN THE 2015 01:31:08,600 --> 01:31:09,760 PROGRAM, DISCUSSION OF SESSION 2016 01:31:09,760 --> 01:31:10,240 1. 2017 01:31:10,240 --> 01:31:16,080 WE CAN NOW HAVE A DISCUSSION. 2018 01:31:16,080 --> 01:31:18,560 SO, BOTH PRESENTERS COULD ASK 2019 01:31:18,560 --> 01:31:20,000 QUESTIONS AND ALSO PARTICIPANTS 2020 01:31:20,000 --> 01:31:25,600 IN THE ZOOM AND THEN I HOPE THAT 2021 01:31:25,600 --> 01:31:27,160 COLLEAGUES COULD ALSO TELL US 2022 01:31:27,160 --> 01:31:29,080 ABOUT THE QUESTIONS FROM OTHER 2023 01:31:29,080 --> 01:31:30,680 PARTS OF THE AUDIENCE. 2024 01:31:30,680 --> 01:31:34,600 I SEE A LOT OF QUESTIONS HAVE 2025 01:31:34,600 --> 01:31:37,040 BEEN ASKED ALREADY IN THE CHAT 2026 01:31:37,040 --> 01:31:42,520 SO MAYBE WE CAN GO AND MAYBE 2027 01:31:42,520 --> 01:31:43,520 ALEXEY COULD YOU ASK -- I SEE 2028 01:31:43,520 --> 01:31:45,840 YOU HAVE A QUESTION MAYBE YOU 2029 01:31:45,840 --> 01:31:52,720 CAN JUST TELL YOURSELF YOU ARE 2030 01:31:52,720 --> 01:32:01,240 ON MUTE. 2031 01:32:01,240 --> 01:32:04,560 >>THE OS SELLATOR IMPROVED THE 2032 01:32:04,560 --> 01:32:05,960 LIFESPAN AND NOT THE MAXIMUM AND 2033 01:32:05,960 --> 01:32:07,520 I JUST TAUGHT ABOUT ASKING YOU, 2034 01:32:07,520 --> 01:32:08,920 CAN YOU COMMENT ON THAT WHAT 2035 01:32:08,920 --> 01:32:10,120 WOULD BE YOUR THOUGHT OF 2036 01:32:10,120 --> 01:32:11,880 INCLUDING THE MAXIMUM IS THAT 2037 01:32:11,880 --> 01:32:14,920 POSSIBLE IN THE EAST? 2038 01:32:14,920 --> 01:32:17,760 >>THIS IS A GREAT QUESTION. 2039 01:32:17,760 --> 01:32:20,200 SO, I GUESS OUR CURRENT 2040 01:32:20,200 --> 01:32:23,080 HYPOTHESIS FOR THIS ENGINEERING 2041 01:32:23,080 --> 01:32:26,480 WE'RE ONLY LOOKING AT TWO MAJOR 2042 01:32:26,480 --> 01:32:27,920 FACTORS AND THE SILENCING PATH 2043 01:32:27,920 --> 01:32:30,720 WAY AND THE OTHER IS 2044 01:32:30,720 --> 01:32:31,760 MITOCHONDRIAL PATHWAY SO THERE 2045 01:32:31,760 --> 01:32:33,120 HAS TO BE OTHER FACTORS WE HAVE 2046 01:32:33,120 --> 01:32:34,760 NOT CONSIDERED OR WE HAVE NOT 2047 01:32:34,760 --> 01:32:37,800 CHARACTERIZED DURING THE AGING 2048 01:32:37,800 --> 01:32:38,880 PROCESS. 2049 01:32:38,880 --> 01:32:44,320 IT OF SEEMS LIKE OUR OSCILLATOR, 2050 01:32:44,320 --> 01:32:48,240 REALLY PROVIDED GOOD CONDITION 2051 01:32:48,240 --> 01:32:49,880 FOR BOTH PATHWAYS HOWEVER THE 2052 01:32:49,880 --> 01:32:50,720 CONTROLS STILL DIE. 2053 01:32:50,720 --> 01:32:52,960 THIS MUST BE SOME OTHER PATHWAYS 2054 01:32:52,960 --> 01:32:56,240 THAT IS IS NOT EFFECTIVE SO THIS 2055 01:32:56,240 --> 01:32:58,320 MAY BE WITH THE LIFESPAN WE CAN 2056 01:32:58,320 --> 01:33:03,440 SEE AND WHILE THE OTHER FROM THE 2057 01:33:03,440 --> 01:33:05,120 SCREEN MAY ALREADY FACTOR THAT 2058 01:33:05,120 --> 01:33:06,880 PATHWAY SO THAT WE SEE SIMILAR 2059 01:33:06,880 --> 01:33:07,600 MAXIMUM PATHWAYS. 2060 01:33:07,600 --> 01:33:10,200 SO IF THEY CAN IDENTIFY MORE 2061 01:33:10,200 --> 01:33:12,800 PATHWAYS, MORE FACTORS, I WOULD 2062 01:33:12,800 --> 01:33:14,600 THINK WE CAN FURTHER EXPAND THE 2063 01:33:14,600 --> 01:33:15,400 LAB. 2064 01:33:15,400 --> 01:33:19,040 SO THAT'S JUST THE IDEA. 2065 01:33:19,040 --> 01:33:20,600 >>THANK YOU. 2066 01:33:20,600 --> 01:33:23,040 >>I SEE THAT YOU PUT WET TO ME. 2067 01:33:23,040 --> 01:33:24,000 IF YOU WANT TO ASK? 2068 01:33:24,000 --> 01:33:27,600 >>YES, I WAS GOING TO ASK YOU 2069 01:33:27,600 --> 01:33:29,840 ABOUT THE IF THERE'S A LIMITED 2070 01:33:29,840 --> 01:33:33,800 WINDOW OF TIME THAT THAT'S 2071 01:33:33,800 --> 01:33:34,680 EFFECTIVE? 2072 01:33:34,680 --> 01:33:38,920 >>WE TRIED FOR THREE MONTHS AND 2073 01:33:38,920 --> 01:33:40,720 ONE MONTH AND THE EFFECT BASED 2074 01:33:40,720 --> 01:33:42,880 ON THE CLOCKS IS MUCH STRONGER 2075 01:33:42,880 --> 01:33:44,760 WHEN WE DO IT FROM THREE MONTHS 2076 01:33:44,760 --> 01:33:46,920 AND IN ONE MONTH, WE STILL SEE 2077 01:33:46,920 --> 01:33:48,800 THE REGENERATION AS WELL BUT NOT 2078 01:33:48,800 --> 01:33:50,000 AS STRONG. 2079 01:33:50,000 --> 01:33:51,520 INTERESTINGLY, WHEN THE MICE AND 2080 01:33:51,520 --> 01:33:53,960 LOOK FOR LIFESPAN WE DO OBSERVE 2081 01:33:53,960 --> 01:33:54,840 CHANGES IN LIFESPAN MEANING THAT 2082 01:33:54,840 --> 01:33:57,080 THE MICE LIVE LONGER AND 2083 01:33:57,080 --> 01:33:59,440 HOWEVER, THE EFFECT IS SMALLER 2084 01:33:59,440 --> 01:34:01,600 RELATIVE TO THE CHANGES IN 2085 01:34:01,600 --> 01:34:02,920 BIOLOGICAL AGE SO MY IMPRESSION 2086 01:34:02,920 --> 01:34:05,880 IS THIS EFFECT DIMINISHES OVER 2087 01:34:05,880 --> 01:34:06,480 TIME. 2088 01:34:06,480 --> 01:34:08,480 IT'S STILL SIGNIFICANT ENOUGH TO 2089 01:34:08,480 --> 01:34:09,960 OBSERVE DIFFERENCES LATE IN LIFE 2090 01:34:09,960 --> 01:34:11,640 BUT IT'S MUCH STRONGER AT THE 2091 01:34:11,640 --> 01:34:15,440 TIME WHEN THE MICE ARE SEPARATED 2092 01:34:15,440 --> 01:34:17,160 AND FADES AWAY. 2093 01:34:17,160 --> 01:34:19,040 IT'S NOT MORE EXPERIMENTS NEED 2094 01:34:19,040 --> 01:34:22,040 TO BE DONE IN THAT DIRECTION. 2095 01:34:22,040 --> 01:34:22,280 SO -- 2096 01:34:22,280 --> 01:34:24,120 >>CAN I ASK ANOTHER QUESTION? 2097 01:34:24,120 --> 01:34:25,360 >>OF COURSE, YEAH. 2098 01:34:25,360 --> 01:34:30,360 >>BECAUSE I NOTICED IN YOUR 2099 01:34:30,360 --> 01:34:32,760 CLOCK AND ALSO OTHER CLOCKS FROM 2100 01:34:32,760 --> 01:34:34,880 ALEXEY, THIS PHENOMENON, WE'VE 2101 01:34:34,880 --> 01:34:38,080 COME ACROSS TOO THAT IF YOU TRY 2102 01:34:38,080 --> 01:34:40,560 TO BUILD THE TRUST WITH THE 2103 01:34:40,560 --> 01:34:42,920 OMICS CLOCK, AND MOST OF THE 2104 01:34:42,920 --> 01:34:48,280 TIME YOU END UP WITH A 2105 01:34:48,280 --> 01:34:50,000 PREDICTING A YOUNGER PEOPLE TO 2106 01:34:50,000 --> 01:34:52,320 BE OLD EVERY AND PREDICTING 2107 01:34:52,320 --> 01:34:54,360 OLDER PEOPLE TO BE YOUNGER. 2108 01:34:54,360 --> 01:34:56,600 THERE'S A BUY AS AND WE'VE SEEN 2109 01:34:56,600 --> 01:35:00,000 THIS IN MANY STUDIES AND IN OUR 2110 01:35:00,000 --> 01:35:01,760 ANALYSIS TOO. 2111 01:35:01,760 --> 01:35:03,040 CONSTANT ATTEMPT TO GET RID OF 2112 01:35:03,040 --> 01:35:03,960 THIS BIAS. 2113 01:35:03,960 --> 01:35:07,400 AND WITH THE BIAS WE SEE A 2114 01:35:07,400 --> 01:35:09,880 BIOLOGICAL ISSUE THAT THERE ARE 2115 01:35:09,880 --> 01:35:12,720 A LIMIT IN WHAT CAN COULD WITH 2116 01:35:12,720 --> 01:35:14,760 OMICS OR MODULATION DATA FOR 2117 01:35:14,760 --> 01:35:17,480 PREDICTION OF BIOLOGICAL AGE. 2118 01:35:17,480 --> 01:35:18,920 I DON'T KNOW IF APPROXIMATE YOU 2119 01:35:18,920 --> 01:35:24,640 GUYS HAVE NOTICED THE SAME 2120 01:35:24,640 --> 01:35:30,440 PROBLEM THAT THERE'S A CLEAR, 2121 01:35:30,440 --> 01:35:34,760 CLEAR BIAS THAT HAPPENS AND IT'S 2122 01:35:34,760 --> 01:35:36,480 HARD TO THINK OF A PATH. 2123 01:35:36,480 --> 01:35:37,400 >>I AGREE. 2124 01:35:37,400 --> 01:35:39,400 WE HAVE THE SAME ACTUALLY. 2125 01:35:39,400 --> 01:35:42,120 IT'S KIND OF CONSISTENTLY. 2126 01:35:42,120 --> 01:35:44,520 AS YOU SAID, IT IT'S HARD TO 2127 01:35:44,520 --> 01:35:46,160 DISTINGUISH WHETHER THIS IS 2128 01:35:46,160 --> 01:35:49,920 REALLY DUE TO SLOW AGING OR KIND 2129 01:35:49,920 --> 01:35:51,800 OF HETEROGENEITY IN THE 2130 01:35:51,800 --> 01:35:54,000 POPULATION OF MORE RAPIDLY AGING 2131 01:35:54,000 --> 01:35:56,640 INDIVIDUALS THAT THEY DIE AND 2132 01:35:56,640 --> 01:35:58,640 THEN IT'S A SELECTION. 2133 01:35:58,640 --> 01:35:59,840 SO SURVIVAL. 2134 01:35:59,840 --> 01:36:02,440 IT'S UNCLEAR BUT IT'S A GOOD 2135 01:36:02,440 --> 01:36:03,880 QUESTION OF THE CLOCK SO 2136 01:36:03,880 --> 01:36:06,200 ACTUALLY, THE STRUCTURE OF THE 2137 01:36:06,200 --> 01:36:08,240 POPULATION OR IT MIGHT BE BOTH. 2138 01:36:08,240 --> 01:36:12,000 THAT IS MY IMPRESSION. 2139 01:36:12,000 --> 01:36:13,920 I WANTED TO JUST MAKE A GENERAL 2140 01:36:13,920 --> 01:36:18,520 COMMENT BECAUSE I WAS REALLY 2141 01:36:18,520 --> 01:36:19,600 EVERYBODY PUBLISHED DATA AND 2142 01:36:19,600 --> 01:36:20,920 SOME OF THE EXCITING PAPERS 2143 01:36:20,920 --> 01:36:21,440 COMING OUT. 2144 01:36:21,440 --> 01:36:24,960 I THINK ALSO I THINK THAT THE 2145 01:36:24,960 --> 01:36:28,720 COMMON THEME WAS THAT EVERYBODY 2146 01:36:28,720 --> 01:36:30,160 HAS MASSIVE DATA AND IT MAKES 2147 01:36:30,160 --> 01:36:32,400 SENSE BECAUSE OF AGING IS A 2148 01:36:32,400 --> 01:36:34,600 SYSTEMIC PROCESS AND I THINK WE 2149 01:36:34,600 --> 01:36:37,320 COME TO REALIZE THAT BASICALLY 2150 01:36:37,320 --> 01:36:38,240 COMPUTATIONAL TOOLS AND MASSIVE 2151 01:36:38,240 --> 01:36:41,040 DATA IS ESSENTIALLY A PART OF 2152 01:36:41,040 --> 01:36:42,960 THE STUDIES CURRENTLY IN THE 2153 01:36:42,960 --> 01:36:45,240 FIELD. 2154 01:36:45,240 --> 01:36:49,160 ALSO, I NOTICED EVERYBODY 2155 01:36:49,160 --> 01:36:50,760 COMMENTED ON (INAUDIBLE) IN 2156 01:36:50,760 --> 01:36:53,880 AGING AND IT'S ANOTHER COMMON 2157 01:36:53,880 --> 01:36:56,320 FEATURE SO, ALSO CHALLENGES AND 2158 01:36:56,320 --> 01:36:57,920 EVERYBODY OF COURSE HIGHLIGHTED 2159 01:36:57,920 --> 01:36:58,720 CHALLENGES. 2160 01:36:58,720 --> 01:37:01,680 I THINK WE AGREE TO DISCUSS SOME 2161 01:37:01,680 --> 01:37:02,240 CHALLENGES. 2162 01:37:02,240 --> 01:37:03,880 I WOULD LIKE TO GIVE THE 2163 01:37:03,880 --> 01:37:06,920 MICROPHONE TO DAVE JONES, 2164 01:37:06,920 --> 01:37:08,480 BECAUSE HE HAS OPERATIONS IN THE 2165 01:37:08,480 --> 01:37:10,960 CHAT AND I SEE A RAISED HAND. 2166 01:37:10,960 --> 01:37:11,200 DAVE. 2167 01:37:11,200 --> 01:37:14,960 >>THANK YOU, VERY MUCH. 2168 01:37:14,960 --> 01:37:25,440 THIS IS JUST TO -- YOU OVER 2169 01:37:31,080 --> 01:37:31,960 ESTIMATE YOUNGER INDIVIDUALS EX 2170 01:37:31,960 --> 01:37:34,800 THIS IS BIAS TOWARDS THE MEAN 2171 01:37:34,800 --> 01:37:37,040 TRAINING DATASET AND THERE'S 2172 01:37:37,040 --> 01:37:38,000 DIFFERENT COMPUTATIONAL 2173 01:37:38,000 --> 01:37:39,080 APPROACHES TO DEALING WITH THAT 2174 01:37:39,080 --> 01:37:41,480 AND I DON'T THINK THE CONSENSUS 2175 01:37:41,480 --> 01:37:44,280 IN THE FIELD REGRESSING OUT THAT 2176 01:37:44,280 --> 01:37:46,600 EFFECT AND THEN USING THE 2177 01:37:46,600 --> 01:37:47,960 CORRECTED AGE GAP TO SEE HOW 2178 01:37:47,960 --> 01:37:50,800 THAT'S RELATED TO BIOLOGY IS THE 2179 01:37:50,800 --> 01:37:52,080 APPROACH WE'RE TAKING NOW BUT 2180 01:37:52,080 --> 01:37:55,280 THERE MAY BE OTHER, BETTER 2181 01:37:55,280 --> 01:37:56,920 SOLUTIONS TO THAT. 2182 01:37:56,920 --> 01:37:59,640 I THINK THAT'S A VERY IMPORTANT 2183 01:37:59,640 --> 01:38:02,800 AREA OF CONVERSATION FOR THE 2184 01:38:02,800 --> 01:38:03,040 FIELD. 2185 01:38:03,040 --> 01:38:04,920 I GUESS THE QUESTION I HAVE IN 2186 01:38:04,920 --> 01:38:07,360 THE CHAT IS KIND OF RELATED TO 2187 01:38:07,360 --> 01:38:07,720 THAT. 2188 01:38:07,720 --> 01:38:08,960 AND THAT WHEN I THINK ABOUT 2189 01:38:08,960 --> 01:38:11,840 THESE BIOLOGICAL CLOCKS, I DO 2190 01:38:11,840 --> 01:38:12,960 THINK ABOUT DIFFERENT SCALES AND 2191 01:38:12,960 --> 01:38:15,880 WE ARE USING DIFFERENT DATA, 2192 01:38:15,880 --> 01:38:19,960 DIFFERENT SCALES TO BUILD THEM. 2193 01:38:19,960 --> 01:38:22,800 AND YOU MENTIONED VERY POOR DATA 2194 01:38:22,800 --> 01:38:24,200 TO USE LIKE CLASSES AND VISITS 2195 01:38:24,200 --> 01:38:28,200 TO THE DOCTOR OFFICES, AND THAT 2196 01:38:28,200 --> 01:38:31,040 MAKES ME THINK OF GOOGLE FLU 2197 01:38:31,040 --> 01:38:32,120 TRENDS IF ANYONE REMEMBERS THAT. 2198 01:38:32,120 --> 01:38:34,480 THAT WAS A VERY POOR WAY TO 2199 01:38:34,480 --> 01:38:36,320 BUILD A DATA FOR THE SAME REASON 2200 01:38:36,320 --> 01:38:42,160 AND THEY CAN PREDICT CEASE OPALU 2201 01:38:42,160 --> 01:38:44,720 FOR SEARCHES IN GOOGLE HOW OFTEN 2202 01:38:44,720 --> 01:38:46,000 PEOPLE SEARCHED FOR FLU. 2203 01:38:46,000 --> 01:38:48,480 IT FIT WELL UNTIL IT DIDN'T. 2204 01:38:48,480 --> 01:38:51,800 I THINK THE SAME SORT OF 2205 01:38:51,800 --> 01:38:54,040 PROBLEMS HERE USES GLASSES TO 2206 01:38:54,040 --> 01:38:54,400 PREDICT AGE. 2207 01:38:54,400 --> 01:38:55,920 YOU ARE NOT MEASURING THE THING 2208 01:38:55,920 --> 01:38:56,880 OF INTEREST. 2209 01:38:56,880 --> 01:38:58,680 AND SO, YOU CAN MEASURE 2210 01:38:58,680 --> 01:39:00,440 DIFFERENT THINGS AT DIFFERENT 2211 01:39:00,440 --> 01:39:02,080 SCALES LIKE OUR COLLEAGUES IN 2212 01:39:02,080 --> 01:39:03,240 CARDIOLOGY WILL PREDICT AGE 2213 01:39:03,240 --> 01:39:05,680 BASED ON THE ECG AND THEY CAN 2214 01:39:05,680 --> 01:39:08,680 ACTUALLY SHOW A REJUVENATION TOO 2215 01:39:08,680 --> 01:39:10,680 IF THEY DO A HEART TRANSPLANT 2216 01:39:10,680 --> 01:39:11,960 THAT OLDER AGE WILL RETURN BACK 2217 01:39:11,960 --> 01:39:15,520 TO NORMAL SO IT'S A RELEVANT 2218 01:39:15,520 --> 01:39:24,120 PIECE OF INFORMATION TO H ESTIME 2219 01:39:24,120 --> 01:39:25,000 BIOLOGICAL AGE. 2220 01:39:25,000 --> 01:39:26,520 THE QUESTION I HAD IN THE CHAT 2221 01:39:26,520 --> 01:39:28,840 WAS, IS THIS A PRIVILEGED SCALE 2222 01:39:28,840 --> 01:39:29,920 WHICH WE SHOULD DEVELOP THESE 2223 01:39:29,920 --> 01:39:31,520 CLOCKS OR IS THERE A GENERAL 2224 01:39:31,520 --> 01:39:35,120 FRAMEWORK FOR THIS EFFORT IN 2225 01:39:35,120 --> 01:39:35,640 GENERAL? 2226 01:39:35,640 --> 01:39:38,960 >>THAT'S A VERY IMPORTANT 2227 01:39:38,960 --> 01:39:39,680 QUESTION. 2228 01:39:39,680 --> 01:39:44,280 MAYBE I'LL ASK PAOLA, IF YOU 2229 01:39:44,280 --> 01:39:47,840 WOULD LIKE TO. 2230 01:39:47,840 --> 01:39:53,680 >>IT SEEMS TO BE A EXTREMELY 2231 01:39:53,680 --> 01:39:59,840 DIFFICULT QUESTION. 2232 01:39:59,840 --> 01:40:02,120 I -- HONESTLY, THE ANSWER IS I 2233 01:40:02,120 --> 01:40:02,640 DON'T KNOW. 2234 01:40:02,640 --> 01:40:03,440 WE'RE TRYING. 2235 01:40:03,440 --> 01:40:05,240 WE DON'T KNOW WHAT WILL BE THE 2236 01:40:05,240 --> 01:40:09,600 RIGHT ANSWER HERE. 2237 01:40:09,600 --> 01:40:16,520 I UNDERSTAND SOMETIMES THERE'S A 2238 01:40:16,520 --> 01:40:18,000 LOT OF CHALLENGE AND WE HAVE 2239 01:40:18,000 --> 01:40:20,000 ECONOMIC MEASURE, RIGHT. 2240 01:40:20,000 --> 01:40:24,480 AND WE SAY IT'S JUST TRIAL AND 2241 01:40:24,480 --> 01:40:28,880 ERROR TO TRY TO SEE WHAT WORKS 2242 01:40:28,880 --> 01:40:30,880 BEST. 2243 01:40:30,880 --> 01:40:36,640 I DON'T REALLY HAVE A STRONG 2244 01:40:36,640 --> 01:40:37,840 POINT OF VIEW HERE. 2245 01:40:37,840 --> 01:40:39,760 I AM STILL TRYING TO UNDERSTAND 2246 01:40:39,760 --> 01:40:41,080 WHAT THIS IS IS THE RIGHT 2247 01:40:41,080 --> 01:40:41,600 ANSWER. 2248 01:40:41,600 --> 01:40:43,200 SO I DON'T KNOW IF ANYBODY 2249 01:40:43,200 --> 01:40:44,880 ANSWERS THAT ARE MORE FOCUSED 2250 01:40:44,880 --> 01:40:46,920 THAN A CLEAR ANSWER YES, WE 2251 01:40:46,920 --> 01:40:48,440 SHOULD GO IN THIS DIRECTION AND 2252 01:40:48,440 --> 01:40:49,400 AT THE MOMENT I'M NOT. 2253 01:40:49,400 --> 01:40:53,320 I DON'T HAVE A CLEAR ANSWER FOR 2254 01:40:53,320 --> 01:41:03,400 THAT. 2255 01:41:13,000 --> 01:41:15,640 THERE'S PHYSIOLOGY OF INTEREST 2256 01:41:15,640 --> 01:41:17,720 AT DIFFERENT SCALES WHICH SHOULD 2257 01:41:17,720 --> 01:41:19,760 BE MODELED AND I THINK THERE'S 2258 01:41:19,760 --> 01:41:21,960 PROBABLY A OF FRAMEWORK FOR 2259 01:41:21,960 --> 01:41:24,240 MODELING ACROSS THEM AND BETWEEN 2260 01:41:24,240 --> 01:41:26,240 THEM AND I THINK THAT'S A MAJOR 2261 01:41:26,240 --> 01:41:27,760 CHALLENGE FOR THE FIELD TO FIND 2262 01:41:27,760 --> 01:41:28,840 OUT WHAT THAT IS AND THE BEST 2263 01:41:28,840 --> 01:41:31,920 WAY TO DO THAT. 2264 01:41:31,920 --> 01:41:34,520 >>SO, I WANT TO GIVE UNEXAMPLE. 2265 01:41:34,520 --> 01:41:36,960 LAST YEAR WE HAD A CONFERENCE 2266 01:41:36,960 --> 01:41:39,240 AND ON AGING. 2267 01:41:39,240 --> 01:41:39,960 AND AT THE GAVE A QUESTIONNAIRE 2268 01:41:39,960 --> 01:41:42,520 TO THE PARTICIPANTS ASKING 2269 01:41:42,520 --> 01:41:43,840 SEVERAL REALLY MOST BASIC 2270 01:41:43,840 --> 01:41:45,440 QUESTIONS IN THE FIELD LIKE WHAT 2271 01:41:45,440 --> 01:41:46,760 IS AGING? 2272 01:41:46,760 --> 01:41:48,480 WHAT CAUSES AGING? 2273 01:41:48,480 --> 01:41:50,840 WHAT DOES AGING BEGIN? 2274 01:41:50,840 --> 01:41:53,720 BUT QUESTIONS LIKE THIS. 2275 01:41:53,720 --> 01:41:55,760 AND WHAT WAS MAZING TO ME WHAT 2276 01:41:55,760 --> 01:42:00,320 IT REVEALED IS THAT THE ANSWERS 2277 01:42:00,320 --> 01:42:04,400 IS THAT SCIENTISTS IN THE FIELD, 2278 01:42:04,400 --> 01:42:05,320 THEY VIEW AGING IN DIFFERENT 2279 01:42:05,320 --> 01:42:05,680 WAYS. 2280 01:42:05,680 --> 01:42:09,800 THEY THINK THAT AGING IS A 2281 01:42:09,800 --> 01:42:13,800 INCREASED CHANCE OF DYING WITH 2282 01:42:13,800 --> 01:42:14,120 AGE. 2283 01:42:14,120 --> 01:42:15,600 IT WAS 10 DIFFERENT CATEGORIES 2284 01:42:15,600 --> 01:42:17,000 LIKE THIS AND OF COURSE, IF IT 2285 01:42:17,000 --> 01:42:19,400 BUILT BY MARKERS OF AGING, YOU 2286 01:42:19,400 --> 01:42:21,160 WOULD BUILD THEM FOR VARIOUS 2287 01:42:21,160 --> 01:42:22,480 DIFFERENT MANIFESTATIONS OF 2288 01:42:22,480 --> 01:42:24,040 AGING SO THEY WOULD BE 2289 01:42:24,040 --> 01:42:24,920 DIFFERENT. 2290 01:42:24,920 --> 01:42:28,000 AND SO TO ME IT'S A VERY SERIOUS 2291 01:42:28,000 --> 01:42:29,080 CHALLENGE BECAUSE MAYBE NOT SO 2292 01:42:29,080 --> 01:42:30,960 MUCH DISCUSSED. 2293 01:42:30,960 --> 01:42:35,760 SO WHEN THEY SAY OF THEY KIND OF 2294 01:42:35,760 --> 01:42:38,680 DISCUSS OMICS AND WHATEVER, 2295 01:42:38,680 --> 01:42:41,200 METHODS AND THEY CONDUCT THE 2296 01:42:41,200 --> 01:42:43,400 CLOCKS BUT THEY TRAIN THEM FOR 2297 01:42:43,400 --> 01:42:45,720 WHAT IS AGING ACTUALLY? 2298 01:42:45,720 --> 01:42:48,840 SO TO ME, THIS IS A KEY QUESTION 2299 01:42:48,840 --> 01:42:50,640 AND EVERYBODY IS COMPLETELY 2300 01:42:50,640 --> 01:42:52,280 DIFFERENT DEFINITION, DIFFERENT 2301 01:42:52,280 --> 01:42:56,080 VIEWS ON AGING. 2302 01:42:56,080 --> 01:42:57,440 SO ALEXEY, DO YOU WANT TO 2303 01:42:57,440 --> 01:42:59,360 CONTINUE TAKING THIS VERY 2304 01:42:59,360 --> 01:43:00,320 SERIOUS QUESTION? 2305 01:43:00,320 --> 01:43:01,520 >>SURE. 2306 01:43:01,520 --> 01:43:12,400 I'M HAPPY TO COULD BE I OBJECT . 2307 01:43:12,400 --> 01:43:14,400 WE DON'T USE TRAINING OR 2308 01:43:14,400 --> 01:43:17,320 DIGRESSION WITH IMAGING. 2309 01:43:17,320 --> 01:43:19,720 REALLY IMAGE THE SIGNATURES AND 2310 01:43:19,720 --> 01:43:20,920 PLOT OR INQUIRE ONE OF THE 2311 01:43:20,920 --> 01:43:23,160 SIGNATURES ARE GOOD FOR AND SO 2312 01:43:23,160 --> 01:43:25,120 WE SAW THAT THEY'RE CORAL EIGHT 2313 01:43:25,120 --> 01:43:31,160 WITH CHRONOLOGICAL AGE AND AS I 2314 01:43:31,160 --> 01:43:37,720 SHOWED THEIR CORRELATED WITH 2315 01:43:37,720 --> 01:43:39,840 LOCOMOTION AND METABOLIC 2316 01:43:39,840 --> 01:43:41,800 PROGRESS SUCH AS MAXIMUM CO2 2317 01:43:41,800 --> 01:43:45,120 WHICH IS CONVENTIONALLY KNOWN AS 2318 01:43:45,120 --> 01:43:45,720 THE CAPACITY. 2319 01:43:45,720 --> 01:43:50,240 AND SO, WE ALSO OBSERVED THOSE 2320 01:43:50,240 --> 01:43:51,200 SIGNATURES HETEROGENEITY 2321 01:43:51,200 --> 01:43:53,320 INCREASE WITH AGE WHICH I GUESS 2322 01:43:53,320 --> 01:43:54,600 REFLECTION OF THE SECOND 2323 01:43:54,600 --> 01:43:57,640 DYNAMICS AND YOU WILL HAVE AN 2324 01:43:57,640 --> 01:43:58,240 INCREASE OF DISORDER AND I GUESS 2325 01:43:58,240 --> 01:43:59,800 IF YOU MEASURE IT CAREFULLY, YOU 2326 01:43:59,800 --> 01:44:03,280 WOULD MAYBE FIND MANY DIFFERENT 2327 01:44:03,280 --> 01:44:05,080 IN PARTICULAR AND THE LANDSCAPE 2328 01:44:05,080 --> 01:44:07,520 OR THE STATE OF THE CELLS IN 2329 01:44:07,520 --> 01:44:11,080 SINGLE CELL PROBABLY DECAY OR 2330 01:44:11,080 --> 01:44:13,240 ALTER INDEPENDENTLY AND THERE 2331 01:44:13,240 --> 01:44:13,960 FOR DIVERGE AND THAT'S WHAT 2332 01:44:13,960 --> 01:44:16,400 WE'RE MEASURING. 2333 01:44:16,400 --> 01:44:26,920 SO, I GUESS, WE TRY TO CON UP 2334 01:44:29,960 --> 01:44:35,320 WITH WAY TO IS TO ADDRESS THE 2335 01:44:35,320 --> 01:44:35,560 PROBLEM. 2336 01:44:35,560 --> 01:44:46,040 >>ABOUT WHAT DO YOU THINK. 2337 01:44:51,560 --> 01:44:54,720 >>DIFFERENT SCALES IN AGING. 2338 01:44:54,720 --> 01:44:57,560 >>YEAH, YEAH. 2339 01:44:57,560 --> 01:45:01,000 I THINK THAT'S VERY SENTIMENTAL 2340 01:45:01,000 --> 01:45:01,240 QUESTIONS. 2341 01:45:01,240 --> 01:45:05,080 SO AS YOU CAN SEE FROM OUR WORK, 2342 01:45:05,080 --> 01:45:07,960 IT'S VERY BASIC SINGLE CELL 2343 01:45:07,960 --> 01:45:10,080 CHANGES. 2344 01:45:10,080 --> 01:45:18,680 SO, HOW TO DEFINITION AND HOW TO 2345 01:45:18,680 --> 01:45:20,880 CONNECT IT AND HOW TO GO ABOUT 2346 01:45:20,880 --> 01:45:24,960 SCALE AND HOW TO CONNECT IT TO 2347 01:45:24,960 --> 01:45:28,120 TISSUE AGING, ANIMAL AGING AND 2348 01:45:28,120 --> 01:45:29,160 DIFFERENT TIME SCALES THERE AND 2349 01:45:29,160 --> 01:45:30,600 WHAT KIND OF DATA WE NEED AND 2350 01:45:30,600 --> 01:45:32,000 WHAT KIND OF DATA WE CAN 2351 01:45:32,000 --> 01:45:34,960 GENERATE IT AND I THINK THERE'S 2352 01:45:34,960 --> 01:45:36,600 A DEFINITELY A VARIOUS STRIKE IN 2353 01:45:36,600 --> 01:45:39,880 QUESTIONS FOR YOU LIKE VERY 2354 01:45:39,880 --> 01:45:43,640 CHALLENGING AND HOW TO EACH 2355 01:45:43,640 --> 01:45:45,680 STATE UNIQUE BECAUSE WE TRACK 2356 01:45:45,680 --> 01:45:46,960 THEIR LIFE SPANS THROUGHOUT THE 2357 01:45:46,960 --> 01:45:48,440 WHOLE LIFESPAN OF EVERY CELL AND 2358 01:45:48,440 --> 01:45:49,800 WE CAN SEE WHAT IS GOING ON 2359 01:45:49,800 --> 01:45:50,600 THERE. 2360 01:45:50,600 --> 01:45:51,960 IT'S A GOOD STARTING POINT BUT 2361 01:45:51,960 --> 01:45:53,720 WHEN WE THINK ABOUT GOING TO A 2362 01:45:53,720 --> 01:45:55,320 SLIGHTLY MORE COMPLEX SYSTEMS 2363 01:45:55,320 --> 01:45:57,400 AND SUDDENLY WE DON'T KNOW WHAT 2364 01:45:57,400 --> 01:46:00,320 TO DO EXPECT, RIGHT, WHAT KIND 2365 01:46:00,320 --> 01:46:03,760 OF DATA WE CAN GENERATE AND IT'S 2366 01:46:03,760 --> 01:46:04,200 LIMITED THERE. 2367 01:46:04,200 --> 01:46:08,120 TO ME THIS IS THE BIGGEST 2368 01:46:08,120 --> 01:46:10,120 CHALLENGE FOR THESE MODELS IN 2369 01:46:10,120 --> 01:46:12,080 THE IF APPROXIMATE WE CAN 2370 01:46:12,080 --> 01:46:14,320 GENERATE I THINK IT'S A PROCESS 2371 01:46:14,320 --> 01:46:16,560 AND WE JUST HAVE TO SEE WHAT 2372 01:46:16,560 --> 01:46:18,200 KIND OF DATA WE CAN GENERATE IN 2373 01:46:18,200 --> 01:46:19,640 AND IT'S BASED ON THAT WE CAN 2374 01:46:19,640 --> 01:46:25,240 GENERATE MODELS TO HOPEFULLY MAP 2375 01:46:25,240 --> 01:46:26,680 THESE MODEL TO UNDERSTAND THE 2376 01:46:26,680 --> 01:46:27,560 AGING PROCESS. 2377 01:46:27,560 --> 01:46:28,960 I DON'T KNOW WHETHER I ANSWERED 2378 01:46:28,960 --> 01:46:30,960 THE QUESTION BUT THAT'S REALLY 2379 01:46:30,960 --> 01:46:34,000 THE KEY CHALLENGE IN OUR STUDY 2380 01:46:34,000 --> 01:46:34,400 NO. 2381 01:46:34,400 --> 01:46:36,280 >>THANK YOU. 2382 01:46:36,280 --> 01:46:40,000 SPEAKING OF CHALLENGES, 2383 01:46:40,000 --> 01:46:45,360 BEFORE -- I JUST WANTED TO ASK 2384 01:46:45,360 --> 01:46:47,760 MANDY BAUTISTA TO ASK BECAUSE 2385 01:46:47,760 --> 01:46:49,200 SHE HAS A NICE QUESTION ABOUT 2386 01:46:49,200 --> 01:46:51,440 THE CHALLENGES AND IT'S TIME TO 2387 01:46:51,440 --> 01:46:52,400 ASK THAT QUESTION. 2388 01:46:52,400 --> 01:46:53,680 >>THANK YOU. 2389 01:46:53,680 --> 01:46:54,200 ABSOLUTELY. 2390 01:46:54,200 --> 01:46:55,320 YOU'VE ALREADY BEEN TOUCHING ON 2391 01:46:55,320 --> 01:46:57,080 THIS IN THE CONVERSATION A 2392 01:46:57,080 --> 01:46:57,360 LITTLE BIT. 2393 01:46:57,360 --> 01:46:59,080 I'D LIKE TO PUSH YOU A LITTLE 2394 01:46:59,080 --> 01:47:01,800 EACH OF YOU, TO TELL ME AND TELL 2395 01:47:01,800 --> 01:47:04,320 ALL OF US, IF YOU HAD TO CHOSE 2396 01:47:04,320 --> 01:47:07,080 JUST ONE, WHAT WOULD YOU PICK AS 2397 01:47:07,080 --> 01:47:09,800 THE MOST IMPORTANT CHALLENGE TO 2398 01:47:09,800 --> 01:47:12,840 OVERCOME THAT UNIQUE TO MODELING 2399 01:47:12,840 --> 01:47:13,680 AGING? 2400 01:47:13,680 --> 01:47:16,160 USING THESE TIMES OF 2401 01:47:16,160 --> 01:47:18,040 COMPUTATIONAL APPROACHES. 2402 01:47:18,040 --> 01:47:19,480 SECONDLY, WHAT WOULD IT TIKE DO 2403 01:47:19,480 --> 01:47:20,080 THAT? 2404 01:47:20,080 --> 01:47:23,680 SO WHAT WOULD IT TAKE TO 2405 01:47:23,680 --> 01:47:24,880 OVERCOME THAT CHALLENGE? 2406 01:47:24,880 --> 01:47:26,440 IT'S NOT AN EASY QUESTION BUT 2407 01:47:26,440 --> 01:47:27,720 I'M THROWING IT OVER TO YOU TO 2408 01:47:27,720 --> 01:47:29,040 SEE WHAT YOUR THOUGHTS ARE. 2409 01:47:29,040 --> 01:47:32,680 >>O. WOULD WOULD LIKE TO BEGIN 2410 01:47:32,680 --> 01:47:33,080 ANSWERING? 2411 01:47:33,080 --> 01:47:39,640 >>I CAN. 2412 01:47:39,640 --> 01:47:41,920 I CAN GIVE MY TWO CENTS. 2413 01:47:41,920 --> 01:47:43,640 I WORK WITH HUMAN DATA, I THINK 2414 01:47:43,640 --> 01:47:46,040 A CHALLENGE TO EVERYTHING WE DO 2415 01:47:46,040 --> 01:47:48,520 IS, AS I MENTIONED EARLIER, WE 2416 01:47:48,520 --> 01:47:50,800 MEASURE THINGS ONE POINT IN 2417 01:47:50,800 --> 01:47:51,440 TIME. 2418 01:47:51,440 --> 01:47:54,200 WE MEASURE ONE THING AND WE TRY 2419 01:47:54,200 --> 01:47:55,760 TO UNDERSTAND A VERY COMPLEX 2420 01:47:55,760 --> 01:47:56,280 SYSTEM. 2421 01:47:56,280 --> 01:47:59,400 SO THE BIG CHALLENGE IS THAT TO 2422 01:47:59,400 --> 01:48:01,440 TRANSITION INTO MODELING 2423 01:48:01,440 --> 01:48:02,520 DYNAMICAL SYSTEM BECAUSE WE'RE 2424 01:48:02,520 --> 01:48:04,520 LOOKING AT THE DYNAMICAL SYSTEM 2425 01:48:04,520 --> 01:48:05,840 WITH A LOT OF FEEDBACK GROUPS 2426 01:48:05,840 --> 01:48:07,640 AND WHAT COULD WE NEED TO DO 2427 01:48:07,640 --> 01:48:13,160 THIS, WE NEED TO HAVE MORE DATA. 2428 01:48:13,160 --> 01:48:15,640 WE NEED MORE DATA, TEMPORAL 2429 01:48:15,640 --> 01:48:20,080 DATA. 2430 01:48:20,080 --> 01:48:21,640 BECAUSE, AND THEN SAMPLING 2431 01:48:21,640 --> 01:48:23,200 ANOTHER QUESTION. 2432 01:48:23,200 --> 01:48:24,680 HOW OFTEN? 2433 01:48:24,680 --> 01:48:26,360 HOW MUCH -- HOW OFTEN IN TIME 2434 01:48:26,360 --> 01:48:28,600 YOU WANT TO MEASURE THINGS AND 2435 01:48:28,600 --> 01:48:30,000 SERVE ON THE CHANGED. 2436 01:48:30,000 --> 01:48:31,840 TO ME THE BIG CHALLENGE WE SEE 2437 01:48:31,840 --> 01:48:34,720 IS THE NEED TO MODEL A DYNAMICAL 2438 01:48:34,720 --> 01:48:37,200 SYSTEM AND WE REALLY DON'T HAVE 2439 01:48:37,200 --> 01:48:38,640 ENOUGH DATA NOW BUT ALSO WE 2440 01:48:38,640 --> 01:48:39,920 DON'T HAVE THE TOOLS TO BE ABLE 2441 01:48:39,920 --> 01:48:41,520 TO DO THIS. 2442 01:48:41,520 --> 01:48:43,040 SO THERE ARE COMPUTATIONAL 2443 01:48:43,040 --> 01:48:47,360 EVIDENCE SO THE INPUT IS REALLY 2444 01:48:47,360 --> 01:48:48,240 LACKING. 2445 01:48:48,240 --> 01:48:51,840 AND TO ME, IT'S REALLY THE MOST 2446 01:48:51,840 --> 01:48:54,000 DIFFICULT THING TO ACHIEVE. 2447 01:48:54,000 --> 01:48:57,640 BUT WE ARE GOING TO ADD A 2448 01:48:57,640 --> 01:48:58,720 LIMITED VISION AND UNDERSTANDING 2449 01:48:58,720 --> 01:49:00,880 IF WE JUST WORK WITH THE CROSS 2450 01:49:00,880 --> 01:49:02,160 SECTIONAL DATA IN HUMANS AND OF 2451 01:49:02,160 --> 01:49:05,080 COURSE WITH AN MA'AM AND OTHER 2452 01:49:05,080 --> 01:49:06,440 EXPERIMENTS ONE CAN GENERATE A 2453 01:49:06,440 --> 01:49:08,920 LOT OF LONGITUDINAL DATA AND 2454 01:49:08,920 --> 01:49:12,080 MEASURE THINGS ASSUMING INFINITE 2455 01:49:12,080 --> 01:49:16,640 YOU CAN MEASURE THINGS IN ANYWAY 2456 01:49:16,640 --> 01:49:18,240 SAMPLE FRAMEWORK. 2457 01:49:18,240 --> 01:49:21,640 >>I SEE YOU. 2458 01:49:21,640 --> 01:49:23,880 WHO WOULD LIKE TO IT? 2459 01:49:23,880 --> 01:49:25,960 >>SURE. 2460 01:49:25,960 --> 01:49:28,080 I THINK ONE OF -- THE MOST 2461 01:49:28,080 --> 01:49:29,760 IMPORTANT THING IS YOU POINTED 2462 01:49:29,760 --> 01:49:31,240 OUT IS BEING THAT TRYING TO 2463 01:49:31,240 --> 01:49:34,680 UNDERSTAND THE COWSAL COWS CAUSY 2464 01:49:34,680 --> 01:49:37,400 AND WHAT IS THE MOST IMPORTANT 2465 01:49:37,400 --> 01:49:39,640 AND THE CULTURAL PHENOMENON AND 2466 01:49:39,640 --> 01:49:44,440 FOR THAT, TWO THINGS COULD BE 2467 01:49:44,440 --> 01:49:47,760 HELPFUL IS IT'S IMPORTANT TO DO 2468 01:49:47,760 --> 01:49:48,920 LONGITUDINAL STUDIES AND OBSERVE 2469 01:49:48,920 --> 01:49:50,600 THE SYSTEM IN PROCESS 2470 01:49:50,600 --> 01:49:53,280 DYNAMICALLY AND SECOND, WE CAN 2471 01:49:53,280 --> 01:49:59,560 THINK ABOUT USING THE TEST 2472 01:49:59,560 --> 01:50:00,400 CAUSALITY AND TO DETERMINE 2473 01:50:00,400 --> 01:50:02,040 WHETHER THE TIME SERIOUS, ONE 2474 01:50:02,040 --> 01:50:05,440 TIME SERIES CAN PREDICT ANOTHER 2475 01:50:05,440 --> 01:50:08,160 AND SAYING IF THERE'S TWO 2476 01:50:08,160 --> 01:50:10,280 PHENOMENON CO REGULATE AND THEN 2477 01:50:10,280 --> 01:50:14,200 ONE OCCURS EARLIER AND IT'S 2478 01:50:14,200 --> 01:50:16,480 POTENTIALLY THE CAUSE THERE'S 2479 01:50:16,480 --> 01:50:18,600 ENOUGH STATISTICAL POWERS TO DO 2480 01:50:18,600 --> 01:50:20,640 THIS SINCE 1969 WHEN THEY 2481 01:50:20,640 --> 01:50:22,280 PROPOSED THAT IT'S BEEN REFINED 2482 01:50:22,280 --> 01:50:23,920 AND OPTIMIZED. 2483 01:50:23,920 --> 01:50:26,280 NOW USING ECONOMICS AND OTHER 2484 01:50:26,280 --> 01:50:26,640 AREAS TOO. 2485 01:50:26,640 --> 01:50:30,160 WHERE IT IS HARD TO DO THE SOME 2486 01:50:30,160 --> 01:50:32,760 IT'S EASIER BUT WHEN IT'S IN 2487 01:50:32,760 --> 01:50:36,240 HUMAN STUDIES FOR EXAMPLE, IT'S 2488 01:50:36,240 --> 01:50:37,680 HARD AND CAUSALITY COULD BE 2489 01:50:37,680 --> 01:50:38,200 HELPFUL. 2490 01:50:38,200 --> 01:50:41,000 >>THANK YOU. 2491 01:50:41,000 --> 01:50:46,480 >>YEAH, I AGREE WITH PAOLA AND 2492 01:50:46,480 --> 01:50:46,960 ALEXEY. 2493 01:50:46,960 --> 01:50:49,720 I THINK DATA IS THE KEY. 2494 01:50:49,720 --> 01:50:53,200 THE DATA, THE TOOL THAT WE CAN 2495 01:50:53,200 --> 01:50:56,960 USE TO MIRROR THE SYSTEM 2496 01:50:56,960 --> 01:50:58,400 DYNAMICALLY AND ALSO PERTURBED 2497 01:50:58,400 --> 01:50:59,560 THE SYSTEM. 2498 01:50:59,560 --> 01:51:02,200 WITH THAT WE CAN START BUILDING 2499 01:51:02,200 --> 01:51:05,280 ON DYNAMIC MODEL MECHANISTIC 2500 01:51:05,280 --> 01:51:05,800 MODEL. 2501 01:51:05,800 --> 01:51:08,040 USE IT AGAIN AND IT'S A UNIQUE 2502 01:51:08,040 --> 01:51:11,040 SYSTEM BUT GOING A LITTLE BIT UP 2503 01:51:11,040 --> 01:51:15,760 TO THE ANIMALS IS A PROBLEM SO I 2504 01:51:15,760 --> 01:51:18,240 THINK TECHNOLOGY IS WHAT WE 2505 01:51:18,240 --> 01:51:21,280 NEED. 2506 01:51:21,280 --> 01:51:22,120 MERITTOUS OF THIS DATA. 2507 01:51:22,120 --> 01:51:25,560 >>YEAH, SO PAYI MAYBE I CAN ALO 2508 01:51:25,560 --> 01:51:26,160 ANSWER. 2509 01:51:26,160 --> 01:51:28,400 BASICALLY I'D LIKE TO REFER TO 2510 01:51:28,400 --> 01:51:29,800 THIS -- I MENTIONED THE SURVEY 2511 01:51:29,800 --> 01:51:31,560 WE GAVE AND THEY ACTUALLY ASKED 2512 01:51:31,560 --> 01:51:33,760 A QUESTION WHAT'S IS THE 2513 01:51:33,760 --> 01:51:35,440 IMPORTANT ANSWER TO THE QUESTION 2514 01:51:35,440 --> 01:51:37,920 IF THE FIELD AND THE MAJORITY OF 2515 01:51:37,920 --> 01:51:39,320 PEOPLE SAY THAT THE MOST 2516 01:51:39,320 --> 01:51:40,880 IMPORTANT IS ACTUALLY TO 2517 01:51:40,880 --> 01:51:42,320 UNDERSTANDING AGING. 2518 01:51:42,320 --> 01:51:44,200 I FULLY AGREE. 2519 01:51:44,200 --> 01:51:46,240 IN FACT, WHEN I TRY TO DEFINE 2520 01:51:46,240 --> 01:51:50,280 WHAT WE DO WE ULTIMATELY TRY TO 2521 01:51:50,280 --> 01:51:51,200 UNDERSTAND AGING. 2522 01:51:51,200 --> 01:51:52,960 IT'S IMPORTANT REALLY WE DEFINE 2523 01:51:52,960 --> 01:51:53,480 IT. 2524 01:51:53,480 --> 01:51:56,640 WE DON'T HAVE TO HAVE A FORMAL 2525 01:51:56,640 --> 01:51:59,400 DEFINITION, BUT JUST IN ESSENCE 2526 01:51:59,400 --> 01:52:02,120 WHAT IS IT BECAUSE THE VIEW IS 2527 01:52:02,120 --> 01:52:04,360 IN A COMPLETELY DIFFERENT WAYS 2528 01:52:04,360 --> 01:52:05,800 AND IF YOU UNDERSTAND, THEN YOU 2529 01:52:05,800 --> 01:52:08,960 COULD TARGET IT AND I THINK 2530 01:52:08,960 --> 01:52:11,640 ULTIMATELY THIS IS THE MOST 2531 01:52:11,640 --> 01:52:12,280 IMPORTANT. 2532 01:52:12,280 --> 01:52:16,000 HOW WE COME TO THAT I DON'T 2533 01:52:16,000 --> 01:52:17,000 KNOW. 2534 01:52:17,000 --> 01:52:18,360 THE NIA SHOULD TAKE A 2535 01:52:18,360 --> 01:52:21,200 PARTNERSHIP MAYBE FORM NEW WAYS 2536 01:52:21,200 --> 01:52:22,080 OR INITIATIVES. 2537 01:52:22,080 --> 01:52:24,080 YOU ARE THE PEOPLE WHO KNOW HOW 2538 01:52:24,080 --> 01:52:25,960 TO DO IT, YEAH. 2539 01:52:25,960 --> 01:52:27,960 >>I MEAN, IF WE HAD THE ANSWER, 2540 01:52:27,960 --> 01:52:29,640 RIGHT, WE WOULDN'T BE HERE. 2541 01:52:29,640 --> 01:52:30,360 >>YOU ARE RIGHT. 2542 01:52:30,360 --> 01:52:31,720 >>THANK YOU. 2543 01:52:31,720 --> 01:52:33,360 THE NEXT QUESTION AND I THINK 2544 01:52:33,360 --> 01:52:35,280 THAT IS THE MOST IMPORTANT 2545 01:52:35,280 --> 01:52:36,640 QUESTION, WHEN YOU HAVE THAT 2546 01:52:36,640 --> 01:52:38,520 ANSWER, YOU CAN THEN KNOW HOW 2547 01:52:38,520 --> 01:52:39,720 YOU ARE COLLECTING YOUR DATA, 2548 01:52:39,720 --> 01:52:41,160 WHY YOU ARE COLLECTING IT AND 2549 01:52:41,160 --> 01:52:42,640 WHAT SCALE, HOW ARE YOU MODELING 2550 01:52:42,640 --> 01:52:45,080 IT AND WHY YOU ARE MODELING ITEL 2551 01:52:45,080 --> 01:52:46,320 AND WHY YOU ARE INTERVENING. 2552 01:52:46,320 --> 01:52:48,840 IF YOU NEED THIS ANSWER, AND I 2553 01:52:48,840 --> 01:52:50,640 THINK LET'S SAY YOU DID THINK OF 2554 01:52:50,640 --> 01:52:53,480 IT AS DYNAMIC PHENOMENON 2555 01:52:53,480 --> 01:52:54,520 MAINTAINING BALANCE FOR FUNCTION 2556 01:52:54,520 --> 01:52:56,840 AT A CERTAIN SCALE OR LEVEL, I 2557 01:52:56,840 --> 01:53:01,520 THINK IT'S REASONABLE AND 2558 01:53:01,520 --> 01:53:02,160 EVERYTHING THAT HANCE SHOWED US 2559 01:53:02,160 --> 01:53:06,160 WHAT APPLY AND YOU WANT TO AVOID 2560 01:53:06,160 --> 01:53:09,560 THE UNHEALTHY FACTOR STATES AND 2561 01:53:09,560 --> 01:53:10,960 FIND WAYS TO GET PEOPLE INTO 2562 01:53:10,960 --> 01:53:12,920 HEALTHY LIMIT CYCLES. 2563 01:53:12,920 --> 01:53:14,120 EACH SCALE OF THE FUNCTION YOU 2564 01:53:14,120 --> 01:53:15,800 ARE INTERESTED IN. 2565 01:53:15,800 --> 01:53:16,480 >>YEAH. 2566 01:53:16,480 --> 01:53:17,880 >>THANK YOU. 2567 01:53:17,880 --> 01:53:19,200 >>I'D LIKE TO SWITCH A LITTLE 2568 01:53:19,200 --> 01:53:23,040 BIT OF DISCUSSION AND ACTUALLY 2569 01:53:23,040 --> 01:53:23,760 ASK NAN A QUESTION. 2570 01:53:23,760 --> 01:53:25,280 IN YOUR TALK, YOU DIDN'T PUT IT 2571 01:53:25,280 --> 01:53:28,320 IN THIS WAY, BUT THE WAY WHEN 2572 01:53:28,320 --> 01:53:31,960 YOU PRESENTED YOUR WORK, I WAS 2573 01:53:31,960 --> 01:53:33,040 THINKING ABOUT AGING AND IT'S 2574 01:53:33,040 --> 01:53:34,840 NOT BEEN REALLY DISCUSSED IN THE 2575 01:53:34,840 --> 01:53:36,360 FIELD BECAUSE WE THINK TISSUE 2576 01:53:36,360 --> 01:53:39,200 AGING AND CELL AGING AND HERE 2577 01:53:39,200 --> 01:53:41,160 IT'S LIKE YOUR WORK REALLY 2578 01:53:41,160 --> 01:53:43,760 IMPLIES THAT THERE'S ALSO A SUB 2579 01:53:43,760 --> 01:53:45,960 CELLULAR SYSTEMS SYSTEMIC AGING 2580 01:53:45,960 --> 01:53:48,880 WHAT'S DO YOU THINK ABOUT IT? 2581 01:53:48,880 --> 01:53:59,320 >>YOU MEAN LIKE SUBCELLULAR'. 2582 01:53:59,320 --> 01:54:00,760 >>THEY MAY CHANGE IN DIFFERENT 2583 01:54:00,760 --> 01:54:01,040 WAYS? 2584 01:54:01,040 --> 01:54:08,000 >>THAT'S RIGHT, THAT'S RIGHT. 2585 01:54:08,000 --> 01:54:10,680 THEY ARE THINKING ABOUT AND THEY 2586 01:54:10,680 --> 01:54:14,520 MAY HAVE TO SAY THE SAME 2587 01:54:14,520 --> 01:54:16,400 FRAMEWORK AND SO THIS IS 2588 01:54:16,400 --> 01:54:18,560 ACTUALLY WHAT WE HAVE IS REALLY 2589 01:54:18,560 --> 01:54:22,080 THINK ABOUT IS THAT HOW THIS 2590 01:54:22,080 --> 01:54:26,480 GENETIC NETWORKS CAN UNDERLINE 2591 01:54:26,480 --> 01:54:28,200 THIS DIFFERENT PATHS AND EVEN AT 2592 01:54:28,200 --> 01:54:30,480 A SINGLE CELL LEVEL SO THIS IS 2593 01:54:30,480 --> 01:54:33,640 IS IDENTICAL CELLS WITHOUT ANY 2594 01:54:33,640 --> 01:54:36,000 OF THE COMPLETE FOR THE CONSTANT 2595 01:54:36,000 --> 01:54:38,040 AND THEY JUST THEY WORK IN THEIR 2596 01:54:38,040 --> 01:54:44,760 AGING PROCESS AND I THINK THERE 2597 01:54:44,760 --> 01:54:55,200 ARE I THINK THAT'S VERY 2598 01:55:11,280 --> 01:55:13,600 INTERESTING BEHAVIOR THAT WE 2599 01:55:13,600 --> 01:55:14,240 SAW. 2600 01:55:14,240 --> 01:55:17,640 THINKING ABOUT EXPANDING AGAIN 2601 01:55:17,640 --> 01:55:20,720 TO SEE THAT IN THE SAME TISSUE, 2602 01:55:20,720 --> 01:55:23,360 OLDER CELLS AS THEIR 2603 01:55:23,360 --> 01:55:24,560 HETEROGENEITY AND TALK ABOUT THE 2604 01:55:24,560 --> 01:55:30,120 EEP GENETIC IF THE CELLS AND 2605 01:55:30,120 --> 01:55:31,640 SIMILAR AGING THAT IS INCREASED 2606 01:55:31,640 --> 01:55:34,480 AND IT'S FANTASTIC ALTERATIONS 2607 01:55:34,480 --> 01:55:37,640 AND WAS UNDERLINE IS AND THE 2608 01:55:37,640 --> 01:55:38,840 TISSUE AND HOW DIFFERENT THAT 2609 01:55:38,840 --> 01:55:41,400 THEY ARE AND ARE THEY CAUSING 2610 01:55:41,400 --> 01:55:42,480 DIFFERENT WAYS TO AGE? 2611 01:55:42,480 --> 01:55:44,480 I THINK THAT'S A PERSPECTIVE 2612 01:55:44,480 --> 01:55:48,840 THAT THEY GET INTO STUDY AIMING. 2613 01:55:48,840 --> 01:55:51,240 I DON'T KNOW WHETHER IT ANSWERS 2614 01:55:51,240 --> 01:55:52,320 YOUR QUESTIONS BUT THIS IS OUR 2615 01:55:52,320 --> 01:55:53,400 PERSPECTIVE. 2616 01:55:53,400 --> 01:55:57,480 FROM THE SIMPLEST POSSIBLE UNION 2617 01:55:57,480 --> 01:55:58,960 FROM AND TRY TO MODEL IT AND 2618 01:55:58,960 --> 01:56:00,920 TROY TO MODEL THE DYNAMICS AND 2619 01:56:00,920 --> 01:56:05,600 THE MECHANISMS OF IT AND BUILD 2620 01:56:05,600 --> 01:56:06,840 ON IT TO SEE IF WE CAN 2621 01:56:06,840 --> 01:56:08,000 UNDERSTAND A MORE COMPLEX SYSTEM 2622 01:56:08,000 --> 01:56:11,760 AND IT'S WHAT WOVE BEEN THINKING 2623 01:56:11,760 --> 01:56:12,480 OF DOING. 2624 01:56:12,480 --> 01:56:14,600 >>I'D LIKE TO ASK NEXT, I'D 2625 01:56:14,600 --> 01:56:17,680 LIKE TO ASK JANINE SIMMONS SHE 2626 01:56:17,680 --> 01:56:18,680 HAS A QUESTION IN THE CHAT IF 2627 01:56:18,680 --> 01:56:23,320 YOU WOULD BE ABLE TO ASK A 2628 01:56:23,320 --> 01:56:23,720 QUESTION. 2629 01:56:23,720 --> 01:56:26,040 >>I THINK I WAS MOSTLY 2630 01:56:26,040 --> 01:56:32,040 RESPONDING TO DAVE JONES BUT I 2631 01:56:32,040 --> 01:56:42,560 WANTED TO SEE SUB SECOND UP TO 2632 01:56:54,640 --> 01:56:56,320 DECADES AND GENERATION PERHAPS? 2633 01:56:56,320 --> 01:56:59,840 >>AND I DID IT AND THE QUESTION 2634 01:56:59,840 --> 01:57:02,480 IS COULD SIMILAR MODELS BE 2635 01:57:02,480 --> 01:57:03,760 APPLIED IF WE HAD SOMETHING 2636 01:57:03,760 --> 01:57:06,320 WORKING AT ONE TEMPLE SCALE 2637 01:57:06,320 --> 01:57:07,800 COULD WE APPLY A SIMILAR MODEL 2638 01:57:07,800 --> 01:57:11,080 AND EXPECT TO APPLY A SIMILAR 2639 01:57:11,080 --> 01:57:13,560 MODEL AT ANOTHER SCALE 2640 01:57:13,560 --> 01:57:15,760 MEANINGFULLY OR DOES EACH HAVE 2641 01:57:15,760 --> 01:57:19,240 TO BE CREATED SEPARATELY? 2642 01:57:19,240 --> 01:57:25,200 >>WE WOULD LIKE TO BEGIN 2643 01:57:25,200 --> 01:57:25,680 ASKING. 2644 01:57:25,680 --> 01:57:29,040 SOMETIMES WE DISCUSS IN THE LAB 2645 01:57:29,040 --> 01:57:30,840 WE ARE YOUNGER IN THE MORNING 2646 01:57:30,840 --> 01:57:31,640 THAN IN THE OPENING AT THE SCALE 2647 01:57:31,640 --> 01:57:37,760 OF THE DAY AND MAYBE AT NIGHT 2648 01:57:37,760 --> 01:57:41,560 ORORNOT SO IT'S UNCLEAR HOW TO 2649 01:57:41,560 --> 01:57:44,560 ACTUALLY ADDRESS IT BECAUSE IT 2650 01:57:44,560 --> 01:57:45,880 WOULD NOT WORK AT THAT SCALE. 2651 01:57:45,880 --> 01:57:49,400 YOU ARE RIGHT SO SOME BIOMARKERS 2652 01:57:49,400 --> 01:57:54,800 THEY WOULD WORK AT DIFFERENT 2653 01:57:54,800 --> 01:57:55,640 SCALES AND OF COURSE IT'S 2654 01:57:55,640 --> 01:57:57,120 WORKING AND IT REFLECTS MORE OF 2655 01:57:57,120 --> 01:58:02,760 THE BIOLOGY THAN AGING THIS THIS 2656 01:58:02,760 --> 01:58:06,120 BECOMES ANOTHER CHALLE CHALLENG. 2657 01:58:06,120 --> 01:58:08,040 EVEN IF IT'S A SMALLER SCALE 2658 01:58:08,040 --> 01:58:12,000 IT'S SOMETHING THEY HAVE NOT 2659 01:58:12,000 --> 01:58:21,120 BEEN DOING. 2660 01:58:21,120 --> 01:58:24,480 >>I SEE AN AND DAVE. 2661 01:58:24,480 --> 01:58:26,800 >>I WOULD NOT ANSWER THAT 2662 01:58:26,800 --> 01:58:31,120 QUESTION BECAUSE THAT'S 2663 01:58:31,120 --> 01:58:41,640 GIGANTIC, HOWEVER, IT'S CLOSER 2664 01:58:41,920 --> 01:58:43,200 TO AN ANSWER BECAUSE THE IDEA 2665 01:58:43,200 --> 01:58:45,200 WOULD GET PRINCIPLE, UNIVERSAL 2666 01:58:45,200 --> 01:58:51,400 PRINCIPLES THAT CAN BE APPLIED 2667 01:58:51,400 --> 01:58:51,960 AT DIFFERENT SCALES. 2668 01:58:51,960 --> 01:58:55,040 OF COURSE THEY NEED NUMERICAL 2669 01:58:55,040 --> 01:58:58,560 ADJUSTMENTS BUT THEY CAN EXPAND 2670 01:58:58,560 --> 01:59:03,880 THEIR WHOLE HIERARCHY OF SCALES 2671 01:59:03,880 --> 01:59:05,280 AND THE TALK WOULD BE DEVELOPING 2672 01:59:05,280 --> 01:59:08,160 A LITTLE BIT ON NOT THESE 2673 01:59:08,160 --> 01:59:12,040 TOPICS, NOT OF COURSE THE 2674 01:59:12,040 --> 01:59:16,360 MOLECULAR LEVEL BUT JUST HEARING 2675 01:59:16,360 --> 01:59:20,160 THE COMMENTS ON WHAT YOU SAID 2676 01:59:20,160 --> 01:59:24,560 THAT YOU MENTAL STUDY STATES AND 2677 01:59:24,560 --> 01:59:26,200 I THINK THAT THIS IS EXACTLY 2678 01:59:26,200 --> 01:59:31,720 WHAT WE SEE AT HIGHER SCALES AND 2679 01:59:31,720 --> 01:59:35,480 CHANGES IN THEY ATTRACT OR TO 2680 01:59:35,480 --> 01:59:38,320 CELL ORGANIZE CRITICALITY AND 2681 01:59:38,320 --> 01:59:43,520 WHICH IS A SCALIST SO THAT I 2682 01:59:43,520 --> 01:59:46,520 MEAN IT'S JUST AN ADDITION 2683 01:59:46,520 --> 01:59:48,320 POSSIBILITY TO APPROACH THIS 2684 01:59:48,320 --> 01:59:50,680 TYPE OF ISSUES. 2685 01:59:50,680 --> 01:59:57,000 >>I AGREE ALSO, LIKE APPLYING 2686 01:59:57,000 --> 01:59:57,960 PRINCIPLES IS A APPROACH. 2687 01:59:57,960 --> 01:59:59,960 I'D LIKE TO ASK DAVE TO MAKE A 2688 01:59:59,960 --> 02:00:01,000 COMMENT OR A QUESTION. 2689 02:00:01,000 --> 02:00:02,120 DAVE JONES. 2690 02:00:02,120 --> 02:00:04,640 >>I JUST WANT TO REINFORCE THAT 2691 02:00:04,640 --> 02:00:06,520 I THINK THE ANSWER IS A COMPLEX 2692 02:00:06,520 --> 02:00:08,520 SYSTEMS APPROACH OR DYNAMICS 2693 02:00:08,520 --> 02:00:08,880 SYSTEM APPROACH. 2694 02:00:08,880 --> 02:00:12,280 YOU CAN GO ACROSS SCALES AND IT 2695 02:00:12,280 --> 02:00:15,000 WILL BE UNIQUE ASPECTS AT EACH 2696 02:00:15,000 --> 02:00:15,520 SCALE. 2697 02:00:15,520 --> 02:00:19,960 IF YOU DO HAVE MODELS AT EACH 2698 02:00:19,960 --> 02:00:22,320 SCALE AND YOU UNDERSTAND HOW YOU 2699 02:00:22,320 --> 02:00:24,200 MIGHT NEED TO RELATE THEM IN 2700 02:00:24,200 --> 02:00:26,720 THIS UNIFIED FRAMEWORK YOU WOULD 2701 02:00:26,720 --> 02:00:27,640 CROSS SCALES. 2702 02:00:27,640 --> 02:00:29,320 AND I REALLY THINK IT'S 2703 02:00:29,320 --> 02:00:30,840 IMPORTANT TO CONSIDER SCALES AND 2704 02:00:30,840 --> 02:00:33,600 ALL THE WORKS AND JUST THINKING 2705 02:00:33,600 --> 02:00:36,480 ABOUT SLEEP-WAKE CYCLES, IT'S A 2706 02:00:36,480 --> 02:00:38,200 PHENOMENON AND WE NEED THAT TO 2707 02:00:38,200 --> 02:00:40,320 MAINTAIN BALANCE IN OUR LIVES. 2708 02:00:40,320 --> 02:00:41,640 AND THERE ARE CERTAINLY 2709 02:00:41,640 --> 02:00:43,200 ENVIRONMENTAL FACTORS WHICH 2710 02:00:43,200 --> 02:00:43,920 WE'LL THROW THAT OFF. 2711 02:00:43,920 --> 02:00:47,440 YOU COULD EVEN WAKE SOMEONE UP 2712 02:00:47,440 --> 02:00:49,320 EVERY NIGHT AND THAT'S GOING TO 2713 02:00:49,320 --> 02:00:51,000 THROW THEIR SLEEP-WAKE CYCLES 2714 02:00:51,000 --> 02:00:51,760 OFF. 2715 02:00:51,760 --> 02:00:53,480 AND THEN THAT'S GOING TO CHANGE 2716 02:00:53,480 --> 02:00:56,720 THE CHEMISTRY AND THE CRYPTOMICS 2717 02:00:56,720 --> 02:01:02,720 AND LOTS OF THINGS BUT YOUR 2718 02:01:02,720 --> 02:01:03,640 INTERVENTIONS AREN'T THAT SCALE 2719 02:01:03,640 --> 02:01:06,200 AND YOU DON'T WANT TO INTERRUPT 2720 02:01:06,200 --> 02:01:07,600 THE PROTEINS AND YOU WOULD WANT 2721 02:01:07,600 --> 02:01:14,440 TO INTERVENE AT THE SHA SLEEP-WE 2722 02:01:14,440 --> 02:01:15,880 CYCLE TO FIX THAT PROBLEM. 2723 02:01:15,880 --> 02:01:17,520 WE NEED UNDERSTANDING THE WAY 2724 02:01:17,520 --> 02:01:18,080 THESE DIFFERENT THINGS ARE 2725 02:01:18,080 --> 02:01:23,160 CONNECTED IN A COMPLEX SYSTEM 2726 02:01:23,160 --> 02:01:24,240 AND OS TORI DYNAMICS. 2727 02:01:24,240 --> 02:01:25,400 >>THANK YOU, DAVE. 2728 02:01:25,400 --> 02:01:26,880 IT'S AN IMPORTANT COMMENT. 2729 02:01:26,880 --> 02:01:29,080 I WOULD LIKE TO ASK ACTUALLY 2730 02:01:29,080 --> 02:01:32,400 MATT AND ALSO HEL HELP LENNY IF 2731 02:01:32,400 --> 02:01:34,400 THERE ARE QUESTIONS FROM THE 2732 02:01:34,400 --> 02:01:34,680 AUDIENCE? 2733 02:01:34,680 --> 02:01:35,840 I DON'T KNOW WHAT IS THE WAY FOR 2734 02:01:35,840 --> 02:01:36,920 THEM TO ASK THOSE QUESTIONS 2735 02:01:36,920 --> 02:01:43,360 BECAUSE WE DON'T SEE THEM HERE. 2736 02:01:43,360 --> 02:01:45,840 >>SO FAR THERE ARE NO 2737 02:01:45,840 --> 02:01:46,640 ADDITIONAL QUESTIONS. 2738 02:01:46,640 --> 02:01:46,880 >>OKAY. 2739 02:01:46,880 --> 02:01:48,000 >>THAT WE HAVE RECEIVED. 2740 02:01:48,000 --> 02:01:50,240 >>FOLKS FROM THE VIEWING THE 2741 02:01:50,240 --> 02:01:52,120 LIVESTREAM DO HAVE QUESTIONS, 2742 02:01:52,120 --> 02:01:54,880 THERE'S THE LIVE FEEDBACK FORM 2743 02:01:54,880 --> 02:01:56,680 THAT WILL GET SENT TO DAVE WHO 2744 02:01:56,680 --> 02:01:58,160 IS MONITORING THOSE AND WE'LL 2745 02:01:58,160 --> 02:02:01,000 PASS THEM THROUGH. 2746 02:02:01,000 --> 02:02:03,200 >>WHILE WE WAIT FOR OTHER 2747 02:02:03,200 --> 02:02:04,400 QUESTIONS, WE CAN CONTINUE OUR 2748 02:02:04,400 --> 02:02:05,120 DISCUSSION. 2749 02:02:05,120 --> 02:02:08,560 AND I SEE ALSO THAT NAN HAD A 2750 02:02:08,560 --> 02:02:12,920 QUESTION FOR ALEXEY. 2751 02:02:12,920 --> 02:02:13,760 >>THAT'S ALL RIGHT. 2752 02:02:13,760 --> 02:02:14,680 THANK YOU. 2753 02:02:14,680 --> 02:02:20,000 SO, FIRST, I WANT TO ALSO I CALL 2754 02:02:20,000 --> 02:02:24,920 I DO THINK THAT THE AT LEAST IT 2755 02:02:24,920 --> 02:02:26,800 CAN BE APPLIED TO DIFFERENT 2756 02:02:26,800 --> 02:02:27,280 SCALES DEFINITELY. 2757 02:02:27,280 --> 02:02:28,840 IT REALLY DEPENDS ON WHAT KIND 2758 02:02:28,840 --> 02:02:30,720 OF DATA WE HAVE AND WHAT KIND OF 2759 02:02:30,720 --> 02:02:34,280 QUESTIONS WE ARE ASKED. 2760 02:02:34,280 --> 02:02:37,440 SO, AT LEAST AGAIN, AS I JUST 2761 02:02:37,440 --> 02:02:38,280 MENTIONED, I'M VERY INTERESTED 2762 02:02:38,280 --> 02:02:41,600 IN THE INCREASE THAT AGAIN EYE 2763 02:02:41,600 --> 02:02:44,360 TEE THAT WE SAW AND I WANT TO 2764 02:02:44,360 --> 02:02:45,520 SEE WHETHER IT'S TOO SPECIFIC 2765 02:02:45,520 --> 02:02:47,040 AND WHAT'S THE CAUSE OF IT AND 2766 02:02:47,040 --> 02:02:48,640 WHETHER IT RELATES TO THE 2767 02:02:48,640 --> 02:02:52,280 DIFFERENCE IN PHENOTYPES OR 2768 02:02:52,280 --> 02:02:53,840 PHYSIOLOGY DIFFERENCE? 2769 02:02:53,840 --> 02:03:00,640 SO, BECAUSE IT'S FANTASTIC. 2770 02:03:00,640 --> 02:03:04,400 IT WAS SERVI SERVICE AS A MATRIO 2771 02:03:04,400 --> 02:03:04,600 AGING. 2772 02:03:04,600 --> 02:03:05,520 >>IT'S WONDERFUL. 2773 02:03:05,520 --> 02:03:08,080 >>WE INCREASE THAT UNIVERSAL' 2774 02:03:08,080 --> 02:03:10,480 AND EVERY TISSUE LOOKED AT. 2775 02:03:10,480 --> 02:03:12,760 IT'S I THINK, WE DIDN'T HAVE 2776 02:03:12,760 --> 02:03:19,600 MUCH OF THE DATA WHERE WE 2777 02:03:19,600 --> 02:03:24,240 CORRELATE ORGAN AND TISSUE MY 2778 02:03:24,240 --> 02:03:26,440 PREDICTION IT WILL CORRELATE 2779 02:03:26,440 --> 02:03:28,840 WITH INCREASE OF HETEROGENEITY 2780 02:03:28,840 --> 02:03:30,760 AND IT'S A WELL-KNOWN PHENOMENON 2781 02:03:30,760 --> 02:03:33,520 WHERE MOST OF THE MEASUREMENTS 2782 02:03:33,520 --> 02:03:39,240 WOULD INCREASE IN AGE. 2783 02:03:39,240 --> 02:03:41,120 WE ORIGINALLY WERE DOING THIS 2784 02:03:41,120 --> 02:03:42,560 AND I DIDN'T HAVE A CHANCE TO 2785 02:03:42,560 --> 02:03:45,160 PRESENT THIS DATA BUT THIS 2786 02:03:45,160 --> 02:03:46,160 HETEROGENEITY COULD BE MEASURED 2787 02:03:46,160 --> 02:03:47,360 AND IN PARTICULAR IN DIFFERENT 2788 02:03:47,360 --> 02:03:49,200 TISSUE BECAUSE IMAGING IS 2789 02:03:49,200 --> 02:03:50,960 BEAUTIFUL AND OF COURSE KNOWN TO 2790 02:03:50,960 --> 02:03:53,160 WORK ON SECTIONS AND WHAT NOT SO 2791 02:03:53,160 --> 02:03:56,640 WE CAN MEASURE HETEROGENEITY 2792 02:03:56,640 --> 02:03:57,840 WITHIN INDIVIDUAL TISSUE 2793 02:03:57,840 --> 02:03:59,640 OBSERVED FOR EXAMPLE WE WORK 2794 02:03:59,640 --> 02:04:02,080 WITH COCHLEA WHERE THE CELLS, 2795 02:04:02,080 --> 02:04:04,240 THEY'RE VERY WELL DEFINED AND WE 2796 02:04:04,240 --> 02:04:07,080 CAN LOOK AT THE YOUNG AND OLD 2797 02:04:07,080 --> 02:04:09,760 CELLS IN THE SAME LOCATION SO WE 2798 02:04:09,760 --> 02:04:11,680 KNOW WE'RE LOOKING AT THE SAME 2799 02:04:11,680 --> 02:04:12,880 250 CELLS THAT MAINTAIN THE 2800 02:04:12,880 --> 02:04:13,800 FUNCTION FOR THE HEARING 2801 02:04:13,800 --> 02:04:15,920 FUNCTION AND WE KNOW THE HEARING 2802 02:04:15,920 --> 02:04:17,320 FUNCTION IS LAST WITH AGE AND WE 2803 02:04:17,320 --> 02:04:20,920 CAN SEE DRAMATIC INCREASE IN 2804 02:04:20,920 --> 02:04:22,560 HETEROGENEITY OF THOSE HAIR 2805 02:04:22,560 --> 02:04:25,440 CELLS WITH RESPECT TO THE 2806 02:04:25,440 --> 02:04:26,400 EPIGENETIC LANDSCAPE. 2807 02:04:26,400 --> 02:04:27,800 SO THAT'S SOMETHING THAT WE CAN 2808 02:04:27,800 --> 02:04:30,240 APPLY FROM MULTIPLE ORGAN AND 2809 02:04:30,240 --> 02:04:33,600 TISSUE AND REALLY UNDERSTAND HOW 2810 02:04:33,600 --> 02:04:35,040 AGING HAPPENS IN THREE DA 2811 02:04:35,040 --> 02:04:40,000 MENTION WITH RESPECT TO 2812 02:04:40,000 --> 02:04:42,000 HETEROGENEITY AND THE FUNCTION 2813 02:04:42,000 --> 02:04:44,120 OF CELLS AND TISSUE AND ORGANS 2814 02:04:44,120 --> 02:04:47,120 AND CELL SAMPLES LIKE NEURONAL 2815 02:04:47,120 --> 02:04:48,760 CONNECTIONS WITH CELLS ET CETERA 2816 02:04:48,760 --> 02:04:51,480 WHETHER THIS FUNCTIONALLY 2817 02:04:51,480 --> 02:04:53,160 CONNECTED CELL SIM POLLS AGE AT 2818 02:04:53,160 --> 02:04:54,960 THE SAME RATE AND WHETHER IT'S 2819 02:04:54,960 --> 02:04:56,800 CORRESPONDING TO THE FUNCTIONSAL 2820 02:04:56,800 --> 02:05:00,320 AT THE TIMER OWE GENEITY AND 2821 02:05:00,320 --> 02:05:00,560 SYSTEM. 2822 02:05:00,560 --> 02:05:04,040 >>SO, WHAT COULD BE THE CAUSE 2823 02:05:04,040 --> 02:05:04,640 OF IT? 2824 02:05:04,640 --> 02:05:06,320 IS IS THAT A CONSEQUENCE OF 2825 02:05:06,320 --> 02:05:09,480 AGING OR IT HAS SOME PROCESS 2826 02:05:09,480 --> 02:05:10,800 THAT DRIVE IT? 2827 02:05:10,800 --> 02:05:13,560 >>IT'S A MILLION DOLLAR 2828 02:05:13,560 --> 02:05:13,840 QUESTION. 2829 02:05:13,840 --> 02:05:14,240 [LAUGHTER] 2830 02:05:14,240 --> 02:05:16,160 >>I GUESS IT WOULD BE ENDLESS 2831 02:05:16,160 --> 02:05:16,920 DEBATES. 2832 02:05:16,920 --> 02:05:19,640 MY SIMPLE ANSWER IS, 2833 02:05:19,640 --> 02:05:22,480 POTENTIALLY, THE SAME SECOND 2834 02:05:22,480 --> 02:05:25,160 DYNAMICS THAT IS UNIVERSALLY 2835 02:05:25,160 --> 02:05:28,520 EXIST ALL OVER AND NOW PEOPLE 2836 02:05:28,520 --> 02:05:30,080 HAVE DISCUSSION AND PAPERS 2837 02:05:30,080 --> 02:05:34,520 APPEARING THAT IT PROBABLY HAS 2838 02:05:34,520 --> 02:05:35,840 THE DERMIS TICK SENSE DEALING 2839 02:05:35,840 --> 02:05:38,040 WITH THE QUANTUM ENTANGLEMENT 2840 02:05:38,040 --> 02:05:40,200 THAT YOU CAN ENTANGLE PRODUCTS 2841 02:05:40,200 --> 02:05:43,560 AND IT'S ENERGY LOST DURING THE 2842 02:05:43,560 --> 02:05:46,200 ENTANGLEMENT AND ESSENTIALLY IT 2843 02:05:46,200 --> 02:05:48,320 MOVES IN ONE DIRECTION AND 2844 02:05:48,320 --> 02:05:49,280 EVERYTHING ELSE IS A 2845 02:05:49,280 --> 02:05:49,640 CONSEQUENCE. 2846 02:05:49,640 --> 02:05:51,160 HOW EXACTLY IT HAPPENS THAT'S 2847 02:05:51,160 --> 02:05:54,200 WHAT WE TRY TO ANSWER AND 2848 02:05:54,200 --> 02:05:57,960 PHRASING IT ELEGANTLY IF WE CAN 2849 02:05:57,960 --> 02:06:00,760 UNDERSTAND THE CAUSES AND 2850 02:06:00,760 --> 02:06:03,720 MECHANISMS IS IS VERY, VERY 2851 02:06:03,720 --> 02:06:04,000 IMPORTANT. 2852 02:06:04,000 --> 02:06:11,720 >>THANK YOU. 2853 02:06:11,720 --> 02:06:13,720 >>THIS THANKS TO THE SCALE AND 2854 02:06:13,720 --> 02:06:16,320 BECAUSE EVEN IF YOU LOOK AT THE 2855 02:06:16,320 --> 02:06:18,080 SYSTEM AT THE CELLULAR LEVEL, 2856 02:06:18,080 --> 02:06:21,080 YOU ARE NOT LOOKING AT THE RIFLE 2857 02:06:21,080 --> 02:06:21,480 COURSE OF CELLS. 2858 02:06:21,480 --> 02:06:25,920 YOU ARE JUST THINKING, ONE 2859 02:06:25,920 --> 02:06:27,240 SNAPSHOT, ONE POINT IN TIME, AND 2860 02:06:27,240 --> 02:06:30,360 SO YOU ARE GOING TO HAVE YOUNG 2861 02:06:30,360 --> 02:06:32,640 CELL, AVERAGE AGE CELL, OLD 2862 02:06:32,640 --> 02:06:34,960 CELL, AND SO, I DON'T KNOW THAT 2863 02:06:34,960 --> 02:06:37,600 WE KEEP MAKING THE SAME -- WE GO 2864 02:06:37,600 --> 02:06:38,880 BACK TO THE SAME ISSUE THAT 2865 02:06:38,880 --> 02:06:40,520 WE'RE NOT LOOKING AT THE 2866 02:06:40,520 --> 02:06:43,400 DYNAMICS AND I DON'T KNOW IF WE 2867 02:06:43,400 --> 02:06:46,000 HAVE THE TOOLS TO EVEN DO THE 2868 02:06:46,000 --> 02:06:48,720 LIFE COURSE EXPERIMENT, AT A 2869 02:06:48,720 --> 02:06:49,440 CELLULAR LEVEL. 2870 02:06:49,440 --> 02:06:51,280 WE SEE HOW THINGS EVOLVE OVER 2871 02:06:51,280 --> 02:06:52,280 TIME BECAUSE THE PROBLEM WE HAVE 2872 02:06:52,280 --> 02:06:54,160 WHEN WE START LOOKING AT THE BIG 2873 02:06:54,160 --> 02:06:55,600 SYSTEM IN HUMANS, IT'S JUST 2874 02:06:55,600 --> 02:06:56,840 THAT'S NOT POSSIBLE. 2875 02:06:56,840 --> 02:07:00,000 BUT A LEVEL OF CELLS, MAY BE 2876 02:07:00,000 --> 02:07:02,400 IT'S POSSIBLE AND YOU CAN THINK 2877 02:07:02,400 --> 02:07:06,040 OF AGING AS -- NOT AGING, I'M 2878 02:07:06,040 --> 02:07:08,560 NOT TRYING ANSWER WHAT IS AGING. 2879 02:07:08,560 --> 02:07:10,200 IT'S A BIG QUESTION. 2880 02:07:10,200 --> 02:07:15,080 BUT WHAT I THINK IF YOU ZOOM IN 2881 02:07:15,080 --> 02:07:18,400 EVEN IN A SYSTEM AND YOU GO ON, 2882 02:07:18,400 --> 02:07:21,400 YOU THINK AT A HIERARCHAL 2883 02:07:21,400 --> 02:07:23,560 STRUCTURE WHERE YOU HAVE AGING 2884 02:07:23,560 --> 02:07:25,240 AT A DIFFERENT SCALE, AS YOU GO 2885 02:07:25,240 --> 02:07:28,080 DOWN TO THE CELLULAR LEVEL IT'S 2886 02:07:28,080 --> 02:07:29,280 CLEAR THINGS HAPPEN FASTER SO 2887 02:07:29,280 --> 02:07:31,200 THERE'S A TURNOVER THAT IS MUCH 2888 02:07:31,200 --> 02:07:35,320 FASTER THAN THE 1020 YEARS OF 2889 02:07:35,320 --> 02:07:36,480 INDIVIDUALS AND WE ARE REALLY 2890 02:07:36,480 --> 02:07:38,520 TRYING TO MODEL THIS HIERARCHY 2891 02:07:38,520 --> 02:07:40,520 OF EVENTS THAT THEN TRANSLATE 2892 02:07:40,520 --> 02:07:42,800 INTO A WHOLE SERIOUS OF EVENTS 2893 02:07:42,800 --> 02:07:46,680 OVER TIME SO WE GO FROM CHANGES 2894 02:07:46,680 --> 02:07:49,240 THAT OCCUR WITHIN SECONDS, 2895 02:07:49,240 --> 02:07:51,000 HOURS, I DON'T KNOW, TO THINGS 2896 02:07:51,000 --> 02:07:54,880 THAT HAPPEN OVER A HUNDRED 2897 02:07:54,880 --> 02:07:55,080 YEARS. 2898 02:07:55,080 --> 02:07:55,480 >>YEAH. 2899 02:07:55,480 --> 02:07:56,520 >>THANK YOU. 2900 02:07:56,520 --> 02:07:58,720 >>OKAY. 2901 02:07:58,720 --> 02:07:58,960 ALEXEY. 2902 02:07:58,960 --> 02:08:01,080 >>YEAH, THANK YOU, I JUST 2903 02:08:01,080 --> 02:08:03,280 MENTIONED THAT I DIDN'T SHOW THE 2904 02:08:03,280 --> 02:08:06,600 DATA BUILDING THE GENETIC ALLEN 2905 02:08:06,600 --> 02:08:07,520 GUINEARED PROBE WHICH CAN ENABLE 2906 02:08:07,520 --> 02:08:09,480 YOU TO FOLLOW THE CHANGING OF 2907 02:08:09,480 --> 02:08:11,360 THE LANDSCAPE AND WE ARE 2908 02:08:11,360 --> 02:08:12,360 ACQUIRING A LOT OF MOVIES AND WE 2909 02:08:12,360 --> 02:08:14,680 CAN FOLLOW, FOR EXAMPLE, THE 2910 02:08:14,680 --> 02:08:15,400 DIVISION OF THE DIFFERENT 2911 02:08:15,400 --> 02:08:19,960 CONDITIONS AND WE CAN FOLLOW THE 2912 02:08:19,960 --> 02:08:21,320 PROPER DEBATE AND A LOT HAS BEEN 2913 02:08:21,320 --> 02:08:24,320 DONE IN CULTURE THAN IN TISSUE 2914 02:08:24,320 --> 02:08:26,040 CULTURE SITUATIONS. 2915 02:08:26,040 --> 02:08:28,600 WE WOULD LOVE TO DO THIS IMAGING 2916 02:08:28,600 --> 02:08:31,200 IN VIVO WITH A WINDOW THAT CAN 2917 02:08:31,200 --> 02:08:32,960 BE INSTALLED IN A LIVE ANIMAL 2918 02:08:32,960 --> 02:08:34,480 AND THE SCALE OF COURSE WOULD BE 2919 02:08:34,480 --> 02:08:38,760 A CHALLENGE BECAUSE IT'S HARD TO 2920 02:08:38,760 --> 02:08:39,840 IMAGE OVER MONTHS. 2921 02:08:39,840 --> 02:08:42,120 WE IMAGE LONGITUDINALLY THE 2922 02:08:42,120 --> 02:08:43,400 BLOOD SAMPLES AND WE CAN SEE 2923 02:08:43,400 --> 02:08:45,680 EVEN IF WE MEASURE THE SAME 2924 02:08:45,680 --> 02:08:47,560 MOUSE EVERY MONTH, THEN THERE'S 2925 02:08:47,560 --> 02:08:55,400 A DRAMATIC, SUFFICIENT 2926 02:08:55,400 --> 02:08:56,840 EPIGENETIC I CAN MOUSE AND OVER 2927 02:08:56,840 --> 02:09:01,280 A COUPLE WEEKS WE ACCUMULATE 2928 02:09:01,280 --> 02:09:06,080 SUFFICIENT CHANGES TO -- THOSE E 2929 02:09:06,080 --> 02:09:07,920 MICE AND IN REAL LIFE, THE 2930 02:09:07,920 --> 02:09:09,120 CHANGES OCCUR PROBABLY IN A 2931 02:09:09,120 --> 02:09:12,560 DAILY BASIS THAT CAN BE 2932 02:09:12,560 --> 02:09:14,920 MEASURABLE THROUGH THE 2933 02:09:14,920 --> 02:09:15,440 EPIGENETIC LAND SCALE. 2934 02:09:15,440 --> 02:09:19,360 >>I HAVE A QUESTION FOR YOU. 2935 02:09:19,360 --> 02:09:22,040 WHEN YOU KIND OF THINK OF YOUR 2936 02:09:22,040 --> 02:09:27,080 NEW METHOD AND COMPARE IT TO 2937 02:09:27,080 --> 02:09:33,160 CLOCKS, WHICH WOULD BE THE MOST 2938 02:09:33,160 --> 02:09:33,440 COMPARABLE? 2939 02:09:33,440 --> 02:09:34,360 IS IT LADIES AND GENTLEMEN 2940 02:09:34,360 --> 02:09:39,000 PROBABL -- WHAT WOULD BE THECLO? 2941 02:09:39,000 --> 02:09:41,880 >>THAT'S A QUESTION GREAT. 2942 02:09:41,880 --> 02:09:43,520 WE DON'T HAVE APP ANSWER YET. 2943 02:09:43,520 --> 02:09:45,120 WE ACTUALLY PROPOSED SOME OF 2944 02:09:45,120 --> 02:09:46,960 THESE STUDIES, YOU KNOW, WE'LL 2945 02:09:46,960 --> 02:09:50,360 SEE WHAT THE STUDY SECTION THINK 2946 02:09:50,360 --> 02:09:51,120 ABOUT THIS. 2947 02:09:51,120 --> 02:09:53,920 THE BEST WOULD BE TO COMPARE TO 2948 02:09:53,920 --> 02:09:55,680 ALL OF THEM OR THE MAJORITY OF 2949 02:09:55,680 --> 02:09:57,680 THEM AS MUCH AS WE CAN MEASURE. 2950 02:09:57,680 --> 02:09:59,600 THE QUESTION OF HOW MUCH CLOCKS 2951 02:09:59,600 --> 02:10:02,160 YOU CAN BUILD THE MEASURE AND I 2952 02:10:02,160 --> 02:10:04,320 BELIEVE THE SINGLE CELL AGE THAT 2953 02:10:04,320 --> 02:10:06,120 YOU DEVELOP RECENTLY WOULD BE 2954 02:10:06,120 --> 02:10:07,920 ONE OF PARTICULAR INTEREST 2955 02:10:07,920 --> 02:10:09,480 BECAUSE OUR IMAGING IS BASED ON 2956 02:10:09,480 --> 02:10:10,760 SINGLE CELLS SO I THINK THEY'LL 2957 02:10:10,760 --> 02:10:13,360 BE INTERESTED TO CORRELATE AND 2958 02:10:13,360 --> 02:10:14,880 THEN UNDERSTAND HOW THIS SPACE 2959 02:10:14,880 --> 02:10:17,280 OF SINGLE CELLS METHYLATION 2960 02:10:17,280 --> 02:10:19,600 CLOCK AND NOT IMAGING SORT OF 2961 02:10:19,600 --> 02:10:21,680 CORRELATES AND CAN IDENTIFY THE 2962 02:10:21,680 --> 02:10:23,560 SAME GROUPS AND SO IT MIGHT BE 2963 02:10:23,560 --> 02:10:25,160 THE ONE THAT WOULD BE MY 2964 02:10:25,160 --> 02:10:25,560 FAVORITE. 2965 02:10:25,560 --> 02:10:30,000 WE NEED DO THE EX PE EXPERIMENT. 2966 02:10:30,000 --> 02:10:30,520 >>THANK YOU. 2967 02:10:30,520 --> 02:10:31,680 I SEE ANY RAISED HANDS. 2968 02:10:31,680 --> 02:10:37,120 >>SO, YES, FIRST FOR PEOPLE WHO 2969 02:10:37,120 --> 02:10:40,040 WATCH AND LISTEN, THROUGH VIDEO 2970 02:10:40,040 --> 02:10:41,480 CAST THERE'S A SEND LIFE 2971 02:10:41,480 --> 02:10:44,000 FEEDBACK BUTTON FOR QUESTIONS. 2972 02:10:44,000 --> 02:10:51,520 AND WE HAVE A QUESTION FROM THE 2973 02:10:51,520 --> 02:10:52,160 VIDEO CAST. 2974 02:10:52,160 --> 02:10:53,720 THANK YOU FOR THIS SESSION FROM 2975 02:10:53,720 --> 02:10:55,520 A BROAD PERSPECTIVE, WHAT IS THE 2976 02:10:55,520 --> 02:10:56,960 MAIN GOAL OF ACCURATELY 2977 02:10:56,960 --> 02:11:00,840 MEASURING AND UNDERSTAND AGING? 2978 02:11:00,840 --> 02:11:02,760 WOULD WE PERHAPS IMPROVE 2979 02:11:02,760 --> 02:11:09,040 KNOWLEDGE AND FURTHER TREATMENT 2980 02:11:09,040 --> 02:11:15,360 AND QUALITY OF LIFESPAN, THANK 2981 02:11:15,360 --> 02:11:15,520 YOU. 2982 02:11:15,520 --> 02:11:18,840 >>THAT'S A GREAT QUESTION. 2983 02:11:18,840 --> 02:11:20,040 WHO WOULD LIKE TO ANSWER? 2984 02:11:20,040 --> 02:11:24,080 >>I DON'T THINK THERE'S A 2985 02:11:24,080 --> 02:11:34,320 UNIQUE ANSWER. 2986 02:11:59,560 --> 02:12:01,520 MAYBE IT'S MORE SUITABLE TO 2987 02:12:01,520 --> 02:12:02,280 ANSWER THIS. 2988 02:12:02,280 --> 02:12:06,560 >>MY TAKE ON IT NOT IS THAT IT 2989 02:12:06,560 --> 02:12:07,760 NEEDS TO QUANTIFY NEEDS FOR 2990 02:12:07,760 --> 02:12:09,520 EVERYTHING WE STUDY. 2991 02:12:09,520 --> 02:12:12,160 WE MUST QUANTIFY, FOR EXAMPLE, 2992 02:12:12,160 --> 02:12:13,320 THE SIMPLEST WAY IS 2993 02:12:13,320 --> 02:12:16,040 INTERVENTIONS AND JUST TEST 2994 02:12:16,040 --> 02:12:16,600 INTERVENTIONS. 2995 02:12:16,600 --> 02:12:18,400 FIND ASSOCIATIONS AND BIO BANKS 2996 02:12:18,400 --> 02:12:20,200 FOR EXAMPLE AND UNDERSTAND THE 2997 02:12:20,200 --> 02:12:22,640 RELATIONSHIP BETWEEN AGING AND 2998 02:12:22,640 --> 02:12:25,240 DEVELOPMENT OR AGING AND BIOLOGY 2999 02:12:25,240 --> 02:12:27,480 AND JUST BASICALLY QUANTIFYING 3000 02:12:27,480 --> 02:12:29,600 IN ESSENCE EVERYTHING. 3001 02:12:29,600 --> 02:12:32,560 SO, THAT'S WHY I THINK THIS IS 3002 02:12:32,560 --> 02:12:34,680 SO EXCITING AND ADVANCE THAT THE 3003 02:12:34,680 --> 02:12:36,240 ABILITY TO QUANTIFY EVEN ALL OF 3004 02:12:36,240 --> 02:12:38,440 THE CHALLENGES THAT I WOULD LINE 3005 02:12:38,440 --> 02:12:40,000 IN MY TALK WHICH IS REALLY 3006 02:12:40,000 --> 02:12:41,080 ADDRESSING AND WE STILL DON'T 3007 02:12:41,080 --> 02:12:42,360 UNDERSTAND EXACTLY WHAT THE 3008 02:12:42,360 --> 02:12:46,440 MEASURE AND HOW THE BEST WAYS TO 3009 02:12:46,440 --> 02:12:49,240 TRAIN THE CLOCKS BUT STILL IT'S 3010 02:12:49,240 --> 02:12:50,120 IMPORTANT. 3011 02:12:50,120 --> 02:12:51,920 JOHN, ALEXEY AND NAN WHAT'S IS 3012 02:12:51,920 --> 02:12:52,480 YOUR TAKE ON IT? 3013 02:12:52,480 --> 02:12:55,560 >>I ABSOLUTELY AGREE WITH YOU. 3014 02:12:55,560 --> 02:12:56,560 QUANTIFICATION, YOU ONLY KNOW 3015 02:12:56,560 --> 02:12:57,680 THINGS AS MUCH AS YOU CAN 3016 02:12:57,680 --> 02:12:58,160 MEASURE THEM. 3017 02:12:58,160 --> 02:12:59,480 IF YOU CANNOT MEASURE YOU CANNOT 3018 02:12:59,480 --> 02:13:00,800 KNOW. 3019 02:13:00,800 --> 02:13:02,280 IT'S A FUNDAMENTAL THING AND THE 3020 02:13:02,280 --> 02:13:03,480 PRECISION OF YOUR KNOWLEDGE 3021 02:13:03,480 --> 02:13:05,760 DIRECTLY CORRELATING OR DEPEND 3022 02:13:05,760 --> 02:13:06,680 ONG PRECISION OF YOUR 3023 02:13:06,680 --> 02:13:08,480 MEASUREMENT BUT FOR THE 3024 02:13:08,480 --> 02:13:09,640 PURPOSES, IN ONE DATA WILL 3025 02:13:09,640 --> 02:13:11,400 FIGURE OUT BETTER HOW TO DO AND 3026 02:13:11,400 --> 02:13:14,760 APPLY AND REJUVENATION YOU STILL 3027 02:13:14,760 --> 02:13:17,680 NEED TO MEASURE IT AND 3028 02:13:17,680 --> 02:13:19,600 PARTICULAR MEASURE VERY 3029 02:13:19,600 --> 02:13:20,040 ACCURATELY. 3030 02:13:20,040 --> 02:13:23,440 SO AGAIN, MEASUREMENT I THINK IS 3031 02:13:23,440 --> 02:13:26,440 ONE OF THE MOST IMPORTANT THING 3032 02:13:26,440 --> 02:13:29,240 THAT WE CAN DEVELOP AND PUSH 3033 02:13:29,240 --> 02:13:31,480 FORWARD OF COURSE WITH THE AIM 3034 02:13:31,480 --> 02:13:34,920 AND THE FUNDAMENTAL QUESTION. 3035 02:13:34,920 --> 02:13:37,520 >>SO, YEAH, FOR US, I THINK THE 3036 02:13:37,520 --> 02:13:41,520 PURPOSE OF MODELING IS REALLY 3037 02:13:41,520 --> 02:13:42,160 FIRST TRYING TO UNDERSTAND THE 3038 02:13:42,160 --> 02:13:44,440 CONSISTENT AND THE BASIC 3039 02:13:44,440 --> 02:13:46,160 MECHANISM LIKE FOR EXAMPLE, WE 3040 02:13:46,160 --> 02:13:47,760 OBSERVE ALL OF THIS INTEREST AND 3041 02:13:47,760 --> 02:13:52,120 BEHAVIOR AS WE SEE LIKE AND WE 3042 02:13:52,120 --> 02:13:57,520 CAN SEE IF WE DO CHANGES THEN 3043 02:13:57,520 --> 02:13:59,040 THERE WILL BE SPACE, WHATS GOING 3044 02:13:59,040 --> 02:14:00,600 ON THERE AND THE MODEL REALLY 3045 02:14:00,600 --> 02:14:02,480 HELP US TO UNDERSTAND ALL OF 3046 02:14:02,480 --> 02:14:04,080 THERE'S A INHIBITION AND 3047 02:14:04,080 --> 02:14:08,080 FEEDBACK AND SO THAT WE CAN HAVE 3048 02:14:08,080 --> 02:14:10,080 STABLE PARTS AND AND THAT KIND 3049 02:14:10,080 --> 02:14:11,720 AND THE MECHANISM THAT WE 3050 02:14:11,720 --> 02:14:12,800 OBSERVED DURING THE PROCESS AND 3051 02:14:12,800 --> 02:14:14,000 TRY TO UNDERSTAND THE MECHANISM 3052 02:14:14,000 --> 02:14:16,280 AND THAT'S THE FIRST GOAL. 3053 02:14:16,280 --> 02:14:20,600 AND IT FUELS SO THE MODEL CAN 3054 02:14:20,600 --> 02:14:27,000 HETCH US O TO PREDICT US AND 3055 02:14:27,000 --> 02:14:29,680 HELP WITH THE INTERVENTION 3056 02:14:29,680 --> 02:14:30,760 STRATEGIES FOR EXAMPLE, IN YEARS 3057 02:14:30,760 --> 02:14:33,040 WHAT WE CAN DO IS WE CAN EVEN 3058 02:14:33,040 --> 02:14:36,720 REVER THIS INHAD BIRTHS AND THE 3059 02:14:36,720 --> 02:14:37,920 MODEL WILL PRO DICTIONARY 3060 02:14:37,920 --> 02:14:42,080 TPRO PREDICT AND ITWILL NOT MAKE 3061 02:14:42,080 --> 02:14:43,520 CELL CAN LIVE LONGER AND WE CAN 3062 02:14:43,520 --> 02:14:46,560 TEST IT AND I THINK THAT'S BIAS 3063 02:14:46,560 --> 02:14:47,520 TO UNDERSTAND THE PROCESS AND 3064 02:14:47,520 --> 02:14:52,280 HOW IT WORKS AND TO PERTURBED IT 3065 02:14:52,280 --> 02:14:54,040 AND CHANGE IT SO WE CAN HAVE 3066 02:14:54,040 --> 02:14:57,840 LONGER LASTING AND THAT'S THE 3067 02:14:57,840 --> 02:14:59,400 GOAL. 3068 02:14:59,400 --> 02:15:00,840 THIS IS A PROOF OF PRINCIPLE BUT 3069 02:15:00,840 --> 02:15:06,120 THE GOAL IS TO EXTEND THAT I 3070 02:15:06,120 --> 02:15:06,400 THINK. 3071 02:15:06,400 --> 02:15:08,040 >>THANK YOU. 3072 02:15:08,040 --> 02:15:12,400 >>SO, I WONDER IF THERE ARE 3073 02:15:12,400 --> 02:15:16,000 ADDITIONAL QUESTIONS FROM 3074 02:15:16,000 --> 02:15:17,960 LIVESTREAM? 3075 02:15:17,960 --> 02:15:20,320 >>NO QUESTIONS RIGHT NOW. 3076 02:15:20,320 --> 02:15:24,200 BUT WE STILL HAVE A FEW MINUTES 3077 02:15:24,200 --> 02:15:26,560 SO IF ANY QUESTIONS COME THROUGH 3078 02:15:26,560 --> 02:15:27,360 WE'LL RELAY THEM. 3079 02:15:27,360 --> 02:15:29,880 >>I HAVE A QUESTION TO PAOLA, 3080 02:15:29,880 --> 02:15:31,360 ACTUALLY, SO YOU ARE MORE THAN 3081 02:15:31,360 --> 02:15:34,560 ANYTHING ELSE THE STUDY OF LONG 3082 02:15:34,560 --> 02:15:39,840 LIVE PEOPLE AND APPLIED OMICS. 3083 02:15:39,840 --> 02:15:42,680 WHAT ARE THE BEST METHODS MAYBE 3084 02:15:42,680 --> 02:15:46,880 BEST OMICS METHODS THAT WOULD 3085 02:15:46,880 --> 02:15:50,160 PREDICT THE OUTCOMES LIKE LATER 3086 02:15:50,160 --> 02:15:54,080 IN LIFE BEFORE CENTENARIANS. 3087 02:15:54,080 --> 02:15:59,680 >>UM -- I CAN -- SO THE ANSWER 3088 02:15:59,680 --> 02:16:01,600 IS I DON'T KNOW YET IF THERE'S 3089 02:16:01,600 --> 02:16:06,600 THE BEST METHOD TO PREDICT IT 3090 02:16:06,600 --> 02:16:09,240 OUTCOMES LIKE LIFESPAN, BUT 3091 02:16:09,240 --> 02:16:13,920 SOMETHING THAT I HAVE NOTICED IS 3092 02:16:13,920 --> 02:16:18,640 THERE IS A -- LET ME PREAMBLE. 3093 02:16:18,640 --> 02:16:20,520 WITH SOME OF THE OMICS WE'RE 3094 02:16:20,520 --> 02:16:21,720 LIMITED WHAT WE MEASURE. 3095 02:16:21,720 --> 02:16:24,800 WE MEASURE ONLY SOMETHING THAT 3096 02:16:24,800 --> 02:16:27,320 IS WE HAVE A LIMITED MEASUREMENT 3097 02:16:27,320 --> 02:16:29,840 SET FOR META BOL OMICS WE 3098 02:16:29,840 --> 02:16:31,880 MEASURE JUST A SMALL HANDFUL OF 3099 02:16:31,880 --> 02:16:42,280 EVERYTHING THAT HAPPENS. 3100 02:16:47,920 --> 02:16:49,880 CORRELATE IT TO AGING AND 3101 02:16:49,880 --> 02:16:51,640 LONGEVITY, A LOT OF THINGS 3102 02:16:51,640 --> 02:16:53,640 CHANGE IN A DRAMATIC, DRAMATIC 3103 02:16:53,640 --> 02:16:54,280 WAY. 3104 02:16:54,280 --> 02:16:56,280 MUCH MORE THAN WHAT WE SEE 3105 02:16:56,280 --> 02:16:58,200 CHANGING WITH THE TRANSCRIPTOMIC 3106 02:16:58,200 --> 02:16:59,960 AND THE GENETICS IS THE HARDEST 3107 02:16:59,960 --> 02:17:00,560 THING. 3108 02:17:00,560 --> 02:17:03,920 SO WE HAVE LOOKED FOR YEARS TO 3109 02:17:03,920 --> 02:17:06,320 SEE WHAT THE GENETIC VARIANTS 3110 02:17:06,320 --> 02:17:08,280 THAT ARE BIG PLAYERS AND IT'S 3111 02:17:08,280 --> 02:17:12,400 TRUE THAT WE HAVE NOT BEEN ABLE 3112 02:17:12,400 --> 02:17:16,360 TO MEASURE CORRUPTS WELL SO WE 3113 02:17:16,360 --> 02:17:18,480 DON'T HAVE THE RIGHT DATA. 3114 02:17:18,480 --> 02:17:20,360 WE HAD A LOT OF CHALLENGES WITH 3115 02:17:20,360 --> 02:17:25,720 THE MEASURES GENETICS AND THINGS 3116 02:17:25,720 --> 02:17:28,680 THAT DETERMINE THE ABILITY TO 3117 02:17:28,680 --> 02:17:32,320 LIVE LONG AND WE SEE MAJOR, 3118 02:17:32,320 --> 02:17:34,120 MAJOR EFFECTS THAT WE DIDN'T 3119 02:17:34,120 --> 02:17:36,080 EXPECT TO THE POINT WHEN YOU 3120 02:17:36,080 --> 02:17:37,840 LOOK AT IT I DID SOMETHING WRONG 3121 02:17:37,840 --> 02:17:39,280 BECAUSE IT'S POSSIBLE THAT 3122 02:17:39,280 --> 02:17:40,360 EVERYTHING CHANGES AND YOU 3123 02:17:40,360 --> 02:17:41,760 REALIZE WHAT WE'RE MEASURING AND 3124 02:17:41,760 --> 02:17:43,080 WHAT WE THINK IS CHANGING WITH 3125 02:17:43,080 --> 02:17:47,160 AGE SO THAT'S WHY EVERYTHING IS 3126 02:17:47,160 --> 02:17:53,320 CHANGES. 3127 02:17:53,320 --> 02:17:54,680 THERE'S A LOT OF LIMITATION IN 3128 02:17:54,680 --> 02:17:58,960 WHAT WE CAN MEASURE IN TERMS OF 3129 02:17:58,960 --> 02:18:00,720 IN METABOLOMICS AND IT'S A BUY 3130 02:18:00,720 --> 02:18:07,400 AS UNANSWERED AND WE CAN MEASURE 3131 02:18:07,400 --> 02:18:14,080 DATA AND WE SEE LESS PREDICT OR 3132 02:18:14,080 --> 02:18:17,760 IN TERMS OF LONGEVITY AND IT'S 3133 02:18:17,760 --> 02:18:19,400 MUCH LESS SO I'M REALLY POSSIBLE 3134 02:18:19,400 --> 02:18:29,880 AND I LOVE TO SEE METABOLOMICS. 3135 02:18:29,880 --> 02:18:32,960 YOU DO BLOOD TEST AND GLUCOSE 3136 02:18:32,960 --> 02:18:34,080 MARKER AND THAT'S THE LEVEL OF 3137 02:18:34,080 --> 02:18:35,080 HOW PEOPLE ARE DOING. 3138 02:18:35,080 --> 02:18:37,920 I THINK THERE'S A LOT TO BE 3139 02:18:37,920 --> 02:18:41,920 DISCOVERED WITH THE MET -- IT'S 3140 02:18:41,920 --> 02:18:43,560 A GOOD ASSESSMENT OF HOW PEOPLE 3141 02:18:43,560 --> 02:18:45,240 ARE AGING. 3142 02:18:45,240 --> 02:18:47,000 >>WE HAVE A LAST MINUTE SO I 3143 02:18:47,000 --> 02:18:50,080 WONDER IF ANYBODY HAS ANY LAST 3144 02:18:50,080 --> 02:18:51,000 IMPORTANT QUESTIONS AND IF NOT, 3145 02:18:51,000 --> 02:18:53,400 I WOULD LIKE TO FINISH WITH ALL 3146 02:18:53,400 --> 02:18:58,080 OF THE PARTICIPANTS ACTUALLY 3147 02:18:58,080 --> 02:18:58,920 STATING WHAT DO YOU THINK IS THE 3148 02:18:58,920 --> 02:19:00,680 MOST IMPORTANT IN THIS CONTEXT? 3149 02:19:00,680 --> 02:19:01,760 JUST VERY BRIEFLY. 3150 02:19:01,760 --> 02:19:04,040 LIKE ONE OR TWO SENTENCES. 3151 02:19:04,040 --> 02:19:07,800 WHAT IS YOUR WISDOM? 3152 02:19:07,800 --> 02:19:11,520 IN THE SPACE OF COMPUTATIONAL 3153 02:19:11,520 --> 02:19:14,480 ANALYSIS IN MOLECULAR SYSTEMS. 3154 02:19:14,480 --> 02:19:17,960 THAT IS OUR SESSION. 3155 02:19:17,960 --> 02:19:22,080 >>IF I -- I DON'T WANT IT TAKE 3156 02:19:22,080 --> 02:19:25,920 OVER BUT TO ME THE BIG CHALLENGE 3157 02:19:25,920 --> 02:19:33,640 I HAVE HAD IS AS WE REALLY GOT A 3158 02:19:33,640 --> 02:19:36,120 LOT OF DATA THE INTEGRATION IS 3159 02:19:36,120 --> 02:19:36,880 REALLY DIFFICULT. 3160 02:19:36,880 --> 02:19:37,960 IT'S REALLY HARD. 3161 02:19:37,960 --> 02:19:40,320 YOU SAY I DO INTEGRATION IT'S 3162 02:19:40,320 --> 02:19:41,280 VERY, VERY HARD. 3163 02:19:41,280 --> 02:19:45,560 VERY, VERY HARD. 3164 02:19:45,560 --> 02:19:47,680 THAT'S A LOT OF CHALLENGES WITH 3165 02:19:47,680 --> 02:19:50,320 THE DATA THAT -- I'M NOT SAYING 3166 02:19:50,320 --> 02:19:51,760 THAT THERE'S NOT SOLUTION, IT'S 3167 02:19:51,760 --> 02:19:55,640 JUST MUCH HARDER THAN WE 3168 02:19:55,640 --> 02:19:58,280 ANTICIPATED. 3169 02:19:58,280 --> 02:20:01,000 ALEXEY, WHAT'S YOU'RE WISDOM. 3170 02:20:01,000 --> 02:20:06,240 >>I THINK THE INTEGRATION OF 3171 02:20:06,240 --> 02:20:07,440 DIFFERENT DATASETS AND KNOWLEDGE 3172 02:20:07,440 --> 02:20:09,880 FROM SINGLE CELL AND MEASUREMENT 3173 02:20:09,880 --> 02:20:11,480 THAT WE CAN DO TO UNDERSTAND HOW 3174 02:20:11,480 --> 02:20:13,520 IT EFFECTS THE FUNCTION OF THE 3175 02:20:13,520 --> 02:20:17,720 ORGAN AND ORGANISM AND 3176 02:20:17,720 --> 02:20:19,640 INTEGRATING THIS DATA IN A 3177 02:20:19,640 --> 02:20:24,560 CONTEXT OF AGING, WHICH OF THIS 3178 02:20:24,560 --> 02:20:28,160 FUNCTION ARE CAUSAL. 3179 02:20:28,160 --> 02:20:29,920 >>THANK YOU, NAN. 3180 02:20:29,920 --> 02:20:32,400 YOU WILL BE THE LAST ONE JUST 3181 02:20:32,400 --> 02:20:32,600 BRIEFLY. 3182 02:20:32,600 --> 02:20:35,920 >>SO JUST, I THINK ABOUT THE 3183 02:20:35,920 --> 02:20:36,280 SCALE. 3184 02:20:36,280 --> 02:20:39,320 I MEAN, I THINK WE TALK A LOT 3185 02:20:39,320 --> 02:20:39,920 ABOUT THE SCALES AS SOMETHING 3186 02:20:39,920 --> 02:20:43,960 LEVEL TO THE TISSUE TO THE 3187 02:20:43,960 --> 02:20:47,080 ANIMAL ANDEL WHERE THE 3188 02:20:47,080 --> 02:20:48,680 PRINCIPLES CAN BE APPLIED TO THE 3189 02:20:48,680 --> 02:20:51,600 VISH YOU AND I THINK ALL THIS 3190 02:20:51,600 --> 02:20:53,320 ADDITIONAL DATA AND THIS WILL BE 3191 02:20:53,320 --> 02:20:57,720 THE NEXT BIG QUESTION TO US. 3192 02:20:57,720 --> 02:20:57,960 YES. 3193 02:20:57,960 --> 02:21:00,480 >>THANK YOU. 3194 02:21:00,480 --> 02:21:03,640 I GIVE THE NIA COLLEAGUES AND I 3195 02:21:03,640 --> 02:21:05,160 WOULD MAYBE CALL THE COFFEE 3196 02:21:05,160 --> 02:21:05,640 BREAK NOW. 3197 02:21:05,640 --> 02:21:10,560 >>YES, I JUST WANTED TO SAY 3198 02:21:10,560 --> 02:21:13,600 QUICK THANK YOU FOR SHARING AND 3199 02:21:13,600 --> 02:21:18,960 ALL OUR PANELISTS AND DISCUSS 3200 02:21:18,960 --> 02:21:23,440 APARTDISCUSSANTS FOR ILLUMINATID 3201 02:21:23,440 --> 02:21:24,280 EXCITING SESSIONS AND I WILL 3202 02:21:24,280 --> 02:21:26,640 HAVE A LARGER SUMMARY AT END OF 3203 02:21:26,640 --> 02:21:29,920 THE DAY AND YES, THEY'RE 3204 02:21:29,920 --> 02:21:30,640 TRANSITIONING TO A BREAK. 3205 02:21:30,640 --> 02:21:33,200 THANK YOU SO MUCH. 3206 02:21:33,200 --> 02:21:35,560 >>THE COFFEE BREAK IS GOING TO 3207 02:21:35,560 --> 02:21:37,560 WORK FOR FOLKS, THIS IS AN 3208 02:21:37,560 --> 02:21:39,960 OPPORTUNITY FOR THE PANELISTS TO 3209 02:21:39,960 --> 02:21:42,000 INTERACT CASUALTY AND WE'LL GO 3210 02:21:42,000 --> 02:21:43,800 TO A ZOOM BREAKOUT SESSION AND 3211 02:21:43,800 --> 02:21:46,840 SO THIS WILL NOT BE LIVESTREAMED 3212 02:21:46,840 --> 02:21:49,440 SO GRAB SOME COFFEE AND TAKE A 3213 02:21:49,440 --> 02:21:50,720 BREAK IF YOU NEED TO BUT THEN 3214 02:21:50,720 --> 02:21:52,640 COME BACK AND IT'S AN 3215 02:21:52,640 --> 02:21:53,680 OPPORTUNITY TO CHAT WITH EACH 3216 02:21:53,680 --> 02:21:54,920 OTHER INFORMALLY. 3217 02:21:54,920 --> 02:21:56,440 THOSE OF YOU ON THE LIVESTREAM, 3218 02:21:56,440 --> 02:22:00,400 WE'LL BE ON BREAK UNTIL 3:30. 3219 02:22:00,400 --> 02:22:01,640 WE'LL THROW UP A SLIDE SO YOU 3220 02:22:01,640 --> 02:22:03,640 HAVE THAT. 3221 02:22:03,640 --> 02:22:05,680 WELCOME BACK FOLKS FROM THE 3222 02:22:05,680 --> 02:22:06,160 BREAK. 3223 02:22:06,160 --> 02:22:07,880 IF YOU WERE ON THE LIVESTREAM, 3224 02:22:07,880 --> 02:22:09,600 AND FOR THOSE OF US WHO ARE IN 3225 02:22:09,600 --> 02:22:12,200 COFFEE HOUR, WE HAD A ROUSING 3226 02:22:12,200 --> 02:22:13,520 DISCUSSION ABOUT SORT OF SLEEP 3227 02:22:13,520 --> 02:22:18,720 AND THE PURPOSE AGING. 3228 02:22:18,720 --> 02:22:23,080 I WILL PASS THE BALL OVER TO 3229 02:22:23,080 --> 02:22:25,600 DAVID JONES AT THE MAYO CLINIC 3230 02:22:25,600 --> 02:22:33,000 WCLINICWHO WILL LEAD OUR NEXT S. 3231 02:22:33,000 --> 02:22:33,640 >>David Jones: THANK YOU, VERY 3232 02:22:33,640 --> 02:22:35,880 MUCH. 3233 02:22:35,880 --> 02:22:38,400 I'M DAVE JONES, A BEHAVIORAL 3234 02:22:38,400 --> 02:22:40,600 NEUROLOGIST PRACTICING AT THE 3235 02:22:40,600 --> 02:22:43,480 MATE MAYO CLINIC. 3236 02:22:43,480 --> 02:22:44,800 DIRECTOR OF ARTIFICIAL 3237 02:22:44,800 --> 02:22:48,000 INTELLIGENCE AND IT'S MY 3238 02:22:48,000 --> 02:22:51,320 PLEASURE TO INTRODUCE EARL 3239 02:22:51,320 --> 02:22:52,600 MILLER FROM MASSACHUSETTS I AM 3240 02:22:52,600 --> 02:22:59,600 SORRY MASS -- AND HE WILLSET THS 3241 02:22:59,600 --> 02:23:00,560 LARGE-SCALE INFORMATION OF THE 3242 02:23:00,560 --> 02:23:03,400 BRAIN WHICH IS A VERY EXCELLENT 3243 02:23:03,400 --> 02:23:06,960 FRAMEWORK FOR THE REST OF THE 3244 02:23:06,960 --> 02:23:14,040 SESSION AND THEN ANA SOLODKIN 3245 02:23:14,040 --> 02:23:15,880 WILL TALK ABOUT BIOLOGICAL MODEL 3246 02:23:15,880 --> 02:23:18,160 THAT'S CAN GENERATE PATTERNS AT 3247 02:23:18,160 --> 02:23:21,480 THIS SCALE AND RELATING THE 3248 02:23:21,480 --> 02:23:23,720 DEMENTIA AND WE'LL TAKE A BREAK 3249 02:23:23,720 --> 02:23:26,760 AND THEN I'LL TALK ABOUT SOME 3250 02:23:26,760 --> 02:23:29,240 CLINICAL APPLICATIONS OF USING 3251 02:23:29,240 --> 02:23:31,640 PATTERNS AT THIS SCALE AND IN A 3252 02:23:31,640 --> 02:23:32,600 CONCEPTUAL FRAMEWORK THAT YOU 3253 02:23:32,600 --> 02:23:35,920 CAN USE TO REASON ABOUT AND TO 3254 02:23:35,920 --> 02:23:40,480 BE USED IN THE CLINIC AND 3255 02:23:40,480 --> 02:23:42,840 CONCLUDE WITH DANI BASSETT 3256 02:23:42,840 --> 02:23:44,280 TALKING ABOUT HOW WE MIGHT BE 3257 02:23:44,280 --> 02:23:45,480 ABLE TO CONTROL THESE. 3258 02:23:45,480 --> 02:23:46,280 THERE'S SOME RELATIONSHIP 3259 02:23:46,280 --> 02:23:50,880 BETWEEN CONTROL THEORY AND THE 3260 02:23:50,880 --> 02:23:59,200 SCALE GIVING US A FRAMEWORK FOR 3261 02:23:59,200 --> 02:23:59,560 INTERVENTIONS. 3262 02:23:59,560 --> 02:24:06,600 >>I'LL SHARE MY SCREEN. 3263 02:24:06,600 --> 02:24:09,280 HERE WE GO. 3264 02:24:09,280 --> 02:24:10,200 ALL RIGHT. 3265 02:24:10,200 --> 02:24:11,240 HELLO, EVERYBODY, THANK YOU FOR 3266 02:24:11,240 --> 02:24:12,560 THE INVITATION TO SPEAK. 3267 02:24:12,560 --> 02:24:13,840 I'M NOT GOING TO SPEAK ABOUT 3268 02:24:13,840 --> 02:24:16,560 AGING, I'M HERE TO SORT OF GIVE 3269 02:24:16,560 --> 02:24:20,200 YOU MY VIEW OF WHERE WE ARE WITH 3270 02:24:20,200 --> 02:24:21,480 SCIENCE AND ORGANIZATION OF THE 3271 02:24:21,480 --> 02:24:24,200 BRAIN ON A LARGE-SCALE. 3272 02:24:24,200 --> 02:24:26,520 PART OF THAT IS TO EXPLAIN HOW 3273 02:24:26,520 --> 02:24:29,360 OUR VIEW OF THE BRAIN IS CHANGED 3274 02:24:29,360 --> 02:24:32,360 OVER THE PAST COUPLE DECADES. 3275 02:24:32,360 --> 02:24:34,000 SO, ABOUT WHAT OUR LAB DOES IS 3276 02:24:34,000 --> 02:24:36,400 STUDY EXECUTIVE BRAIN FUNCTION, 3277 02:24:36,400 --> 02:24:40,360 PLANNING AND FOCUSING ATTENTION 3278 02:24:40,360 --> 02:24:44,280 ET CETERA SO FOURTH AND WE STUDY 3279 02:24:44,280 --> 02:24:45,360 ELECTRICAL SIGNALS IF THE BRAINS 3280 02:24:45,360 --> 02:24:47,600 IN NON HUMAN PRIMATES. 3281 02:24:47,600 --> 02:24:49,400 WE JUST COMPUTATIONAL VOLUME TO 3282 02:24:49,400 --> 02:24:50,720 MAKE SENSE OF THESE SIGNALS AND 3283 02:24:50,720 --> 02:24:52,760 WE WANT TO UNDERSTAND COGNITION. 3284 02:24:52,760 --> 02:24:55,120 IT'S DYSFUNCTION AND DISEASES. 3285 02:24:55,120 --> 02:24:58,800 SUCH AS AUTISM, SCHIZOPHRENIA, 3286 02:24:58,800 --> 02:24:59,520 ADHD. 3287 02:24:59,520 --> 02:25:01,520 NOW, IN EMPLOYING THESE STUDIES, 3288 02:25:01,520 --> 02:25:03,800 WE BEGAN ABOUT 20 YEARS AGO OR 3289 02:25:03,800 --> 02:25:05,840 SO TO BEGIN USING NEW MULTIPLE 3290 02:25:05,840 --> 02:25:07,520 ELECTRODE TECHNOLOGY AND THIS IS 3291 02:25:07,520 --> 02:25:08,320 SIGNIFICANT BECAUSE IN THE 3292 02:25:08,320 --> 02:25:13,040 20th CENTURY, WHEN I WAS A 3293 02:25:13,040 --> 02:25:20,280 GRADUATE STUDENT, WITH A SINGLE 3294 02:25:20,280 --> 02:25:21,600 ELECTRODE WITH I LESS PART OF 3295 02:25:21,600 --> 02:25:22,880 THE FRAMEWORK AND WE HAD TO 3296 02:25:22,880 --> 02:25:24,440 FIGURE OUT THE BRAIN'S PARTS BUT 3297 02:25:24,440 --> 02:25:25,880 IN FACT IN GENERAL, WE FOCUSED 3298 02:25:25,880 --> 02:25:27,880 ON THE BRAIN'S PARTS INDIVIDUAL 3299 02:25:27,880 --> 02:25:30,400 BRAIN AREAS AND SPIKING OF 3300 02:25:30,400 --> 02:25:37,040 SINGLE NEURONS AND WE THOUGHT 3301 02:25:37,040 --> 02:25:47,760 THE AND THERE'S COMPLEXITY GOING 3302 02:25:47,760 --> 02:25:50,200 ON SO NOW WE HAVE THE TECHNOLOGY 3303 02:25:50,200 --> 02:25:51,160 TO RECORD SEALS OF HUNDREDS OF 3304 02:25:51,160 --> 02:25:53,080 MILLIONS OF NEURONS 3305 02:25:53,080 --> 02:25:53,720 SIMULTANEOUSLY. 3306 02:25:53,720 --> 02:25:55,680 AND THIS IS BEGUN TO INCREASE 3307 02:25:55,680 --> 02:25:56,760 OUR UNDERSTANDING OF THE BRAIN 3308 02:25:56,760 --> 02:25:57,840 AND A NETWORK LEVEL. 3309 02:25:57,840 --> 02:25:59,760 IT IS IS EMERGENT PROPERTIES AND 3310 02:25:59,760 --> 02:26:01,280 THESE ARE PROPERTIES IN 3311 02:26:01,280 --> 02:26:02,840 MECHANISMS THAT EMERGE AND YOU 3312 02:26:02,840 --> 02:26:04,880 CAN SEE WITH THE PARTS INTERACT 3313 02:26:04,880 --> 02:26:05,320 AS A WILDER WHOLE. 3314 02:26:05,320 --> 02:26:07,920 YOU CAN'T SEE THEM ONE PART AT A 3315 02:26:07,920 --> 02:26:08,400 TIME. 3316 02:26:08,400 --> 02:26:09,840 I'LL SHOW YOU AN EXAMPLE OF ONE 3317 02:26:09,840 --> 02:26:11,040 OF THEM IN A MINUTE. 3318 02:26:11,040 --> 02:26:15,960 WE USED TO THINK ABOUT SPIKES. 3319 02:26:15,960 --> 02:26:26,440 THINK ABOUT SPIKES TRYING TO 3320 02:26:53,960 --> 02:26:55,400 EXPLAIN HOW THE BRAIN MOVES 3321 02:26:55,400 --> 02:26:56,680 ABSTRACT CONCEPTS AND 3322 02:26:56,680 --> 02:26:57,400 PRINCIPLESES. 3323 02:26:57,400 --> 02:26:59,040 WE TALKED MONKEYS, SHAPE 3324 02:26:59,040 --> 02:27:00,440 CATEGORIES LIKE CATS VERSUS DOGS 3325 02:27:00,440 --> 02:27:02,520 OR WE TALKED TO RECOGNIZE SMALL 3326 02:27:02,520 --> 02:27:12,720 NUMBERS 1-5. 3327 02:27:21,320 --> 02:27:22,440 THEY DON'T LEARN AT THE LEVEL OF 3328 02:27:22,440 --> 02:27:25,920 RULES AND PRINCIPLES AND IT'S 3329 02:27:25,920 --> 02:27:28,200 WHAT YOU EXPECT AND WE WANT TO 3330 02:27:28,200 --> 02:27:36,560 SHOW HOW THE IT'S TOP DOWN AND 3331 02:27:36,560 --> 02:27:39,560 PRODUCE TOP-DOWN CONTROL. 3332 02:27:39,560 --> 02:27:41,360 NOW, WE DID HER EXPERIMENT AND 3333 02:27:41,360 --> 02:27:44,840 WE FOUND IT UNUSUAL AND IT'S 3334 02:27:44,840 --> 02:27:45,680 UNUSUALLY AND IT'S A COUPLE 3335 02:27:45,680 --> 02:27:49,120 DECADES AGO. 3336 02:27:49,120 --> 02:27:57,680 WE USED SO WE HAVE A BETTER 3337 02:27:57,680 --> 02:27:59,000 PICTURE OF THE NEURONS LOOKED 3338 02:27:59,000 --> 02:28:01,640 LIKE AND WE FOUND AND RECORDED 3339 02:28:01,640 --> 02:28:04,800 IN THE PREFRONTAL CORTEX AND WE 3340 02:28:04,800 --> 02:28:06,880 FOUND THESE EFFECTS, CAT VERSUS 3341 02:28:06,880 --> 02:28:09,280 DOG, NUMBERS, UP VERSUS DOWN, 3342 02:28:09,280 --> 02:28:12,120 SAME VERSUS DIFFERENT IF 30% OR 3343 02:28:12,120 --> 02:28:13,160 40% OF THE NEWERRANCE WE 3344 02:28:13,160 --> 02:28:14,800 SELECTED AND THAT IS A LOT OF 3345 02:28:14,800 --> 02:28:16,280 NEURONS AND IT'S LIKE A TASK 3346 02:28:16,280 --> 02:28:17,920 TOOK OVER THE BRAIN AND THE 3347 02:28:17,920 --> 02:28:18,720 PROBLEM WITH THAT AT THE TIME 3348 02:28:18,720 --> 02:28:21,520 WAS THE 20th CENTURY PARADIGM 3349 02:28:21,520 --> 02:28:24,520 SAID THAT EVERY NEURON SHOULD 3350 02:28:24,520 --> 02:28:27,760 HAVE UP WITH PENSION AND THEY DO 3351 02:28:27,760 --> 02:28:30,320 THEIR THING BY COMBINING THEIR 3352 02:28:30,320 --> 02:28:32,080 SIGNAL BY VIRTUAL OF HOW THEY'RE 3353 02:28:32,080 --> 02:28:34,640 WIRED TOGETHER AND YOU START 3354 02:28:34,640 --> 02:28:37,200 WITH SMALL NEURONS IN THE BACK 3355 02:28:37,200 --> 02:28:45,800 OF BRAIN AND DECORRECT THE VISH 3356 02:28:45,800 --> 02:28:56,240 ACTUAL AND AND IT'S WIDELY 3357 02:28:59,920 --> 02:29:01,760 ASSUMED, I BELIEVE, THAT THE 3358 02:29:01,760 --> 02:29:03,160 NEURONS DON'T HAVE ONE PENSION 3359 02:29:03,160 --> 02:29:03,960 ESPECIALLY IN HIGHER CORTICAL 3360 02:29:03,960 --> 02:29:06,360 AREAS AND THERE ARE MULTI 3361 02:29:06,360 --> 02:29:07,640 FUNCTIONAL LEVEL A PROPERTY 3362 02:29:07,640 --> 02:29:09,280 CALLED MIXED SELECTIVITY. 3363 02:29:09,280 --> 02:29:10,600 NOW WHAT IT MIXED SELECTION 3364 02:29:10,600 --> 02:29:13,720 ACTIVITY IS THE WAY WE USED TO 3365 02:29:13,720 --> 02:29:16,840 THINK ABOUT THE BRAIN IS WE 3366 02:29:16,840 --> 02:29:18,360 THOUGHT NEURONS ARE SIMPLE AND 3367 02:29:18,360 --> 02:29:19,320 SPECIALIZED WITH ONE FUNCTION 3368 02:29:19,320 --> 02:29:19,760 ONLY. 3369 02:29:19,760 --> 02:29:24,080 THEY MIGHT DETECT SINGLE 3370 02:29:24,080 --> 02:29:29,040 FEATURES LIKE EDGES THAT PIECE 3371 02:29:29,040 --> 02:29:30,200 TOGETHER TO SOMETHING SO THIS 3372 02:29:30,200 --> 02:29:33,960 EXAMPLE IS NEURONS THAT COMBINE 3373 02:29:33,960 --> 02:29:36,480 COLOR FORM AND ROLLING INTO THE 3374 02:29:36,480 --> 02:29:39,080 ROLLING BALL AND IT MIGHT 3375 02:29:39,080 --> 02:29:40,680 COMBINE FEATURES BUT THEY MAKE 3376 02:29:40,680 --> 02:29:41,040 SENSE TOGETHER. 3377 02:29:41,040 --> 02:29:43,280 IN CONDUCTING THESE EXPERIMENTS, 3378 02:29:43,280 --> 02:29:44,360 USING THESE HIGHER PRINCIPLES 3379 02:29:44,360 --> 02:29:47,280 WE'RE TEACHING THE ANIMAL WE 3380 02:29:47,280 --> 02:29:49,800 FOUND THAT PROPERTY CALLED MIX 3381 02:29:49,800 --> 02:29:51,880 SELECTIVITY IT DID NOT FIT THIS 3382 02:29:51,880 --> 02:29:52,280 TRADITIONAL MOLD. 3383 02:29:52,280 --> 02:29:54,080 THESE NEURONS WERE SELECTIVE FOR 3384 02:29:54,080 --> 02:29:56,000 A COMPLEX COMBINATIONS WITH 3385 02:29:56,000 --> 02:29:57,320 FEATURES WITH NO OBVIOUS 3386 02:29:57,320 --> 02:29:57,800 RELATIONSHIP. 3387 02:29:57,800 --> 02:30:00,320 AND IF YOU STUDY THEM MULTIPLE 3388 02:30:00,320 --> 02:30:02,160 TASK YOU TRAIN THE ANIMAL TO DO 3389 02:30:02,160 --> 02:30:03,480 DIFFERENT TRAFFICS YOU FIND THE 3390 02:30:03,480 --> 02:30:09,320 SAME NEURON WITH DIFFERENT 3391 02:30:09,320 --> 02:30:10,560 FUNCTIONS, IN DIFFERENT TASKS 3392 02:30:10,560 --> 02:30:11,760 AND WE WEREN'T RANDOM AND BACK 3393 02:30:11,760 --> 02:30:13,440 TO THE SAME TASK THE SAME 3394 02:30:13,440 --> 02:30:14,840 CONTEXT AND NEURONS AND THEY DID 3395 02:30:14,840 --> 02:30:16,640 THE SAME THING AND IT'S A REALLY 3396 02:30:16,640 --> 02:30:20,480 DIFFERENT THINGS IN DIFFERENT 3397 02:30:20,480 --> 02:30:30,680 SITUATIONS. 3398 02:30:41,480 --> 02:30:42,960 THE NETWORKS AND THE INFORMATION 3399 02:30:42,960 --> 02:30:44,120 AND THE GRAIN HAS THIS 3400 02:30:44,120 --> 02:30:48,680 INFORMATION AT ITS FINGER TIPS. 3401 02:30:48,680 --> 02:30:50,160 THIS MAKES THE BRAIN SMARTER 3402 02:30:50,160 --> 02:30:52,040 AND A HIGH DID MENTIONAL 3403 02:30:52,040 --> 02:30:53,200 REPRESENTATION SPACE WHERE 3404 02:30:53,200 --> 02:30:54,840 NEURAL REPUTATIONS GET 3405 02:30:54,840 --> 02:30:55,800 COMPLICATED AND CONTAIN MORE 3406 02:30:55,800 --> 02:30:57,320 INFORMATION SO YOU CAN DO MORE 3407 02:30:57,320 --> 02:31:00,400 HIGH-LEVEL STUFF WITH THAT. 3408 02:31:00,400 --> 02:31:03,600 AND ALSO FOR REASONS I WON'T 3409 02:31:03,600 --> 02:31:05,760 EXPLAIN, IT MAKES THE BRAIN GO 3410 02:31:05,760 --> 02:31:08,120 ESSENTIALLY CAPACITY UNLIMITED 3411 02:31:08,120 --> 02:31:10,280 BY DISTRIBUTING THE INFORMATION 3412 02:31:10,280 --> 02:31:11,720 ACROSS MANY DIFFERENT NEURONS SO 3413 02:31:11,720 --> 02:31:13,840 NOW THE BRAIN CAN STORE MUCH 3414 02:31:13,840 --> 02:31:14,800 MORE INFORMATION. 3415 02:31:14,800 --> 02:31:16,240 AND ALL THIS MINGLING 3416 02:31:16,240 --> 02:31:17,040 INFORMATION MEANS THAT THE 3417 02:31:17,040 --> 02:31:19,080 BRAIN, YOU CAN LEARN THINGS 3418 02:31:19,080 --> 02:31:20,240 QUICKLY AND YOU HAVE FLEXIBILITY 3419 02:31:20,240 --> 02:31:23,200 TO CHANGE YOUR MIND WHEN MOMENT 3420 02:31:23,200 --> 02:31:25,440 TO MOMENT. 3421 02:31:25,440 --> 02:31:30,640 HOWEVER, THE PROBLEM IS WITH MIX 3422 02:31:30,640 --> 02:31:32,080 SELECTIVITY, IT'S WHY THEY 3423 02:31:32,080 --> 02:31:34,480 ACCEPTED AND PEOPLE ARE FOR ALL 3424 02:31:34,480 --> 02:31:38,680 OVER THE BRAIN AND NOT THE 3425 02:31:38,680 --> 02:31:41,960 CONTEXT AND BUT MIXED SELECTION 3426 02:31:41,960 --> 02:31:43,120 ACTIVITY HAS A NEW WAY OF 3427 02:31:43,120 --> 02:31:43,960 THINKING ABOUT THE BRAIN. 3428 02:31:43,960 --> 02:31:46,360 WE USED TO THINK EVERY NEURON 3429 02:31:46,360 --> 02:31:48,680 HAD ONE FUNCTION AND WE USED TO 3430 02:31:48,680 --> 02:31:54,040 THINK THAT ANATOMY IS DESTINY 3431 02:31:54,040 --> 02:31:56,480 AND THEY'RE WIRED TOGETHER. 3432 02:31:56,480 --> 02:31:58,840 SO EVERY PERCEPTION, THOUGHT, 3433 02:31:58,840 --> 02:31:59,960 ACTION, EVERYTHING YOUR BRAIN 3434 02:31:59,960 --> 02:32:02,440 DOES HAS A UNIQUE NETWORK AND 3435 02:32:02,440 --> 02:32:02,720 ENSEMBLE. 3436 02:32:02,720 --> 02:32:05,720 I HAVE TWO NETWORKS HERE. 3437 02:32:05,720 --> 02:32:08,120 THE BLUE THOUGHT AND THE RECEIPT 3438 02:32:08,120 --> 02:32:09,480 THOUGHT IS ANOTHER NETWORK AND 3439 02:32:09,480 --> 02:32:10,680 EVERY OTHER THOUGHT YOU MIGHT 3440 02:32:10,680 --> 02:32:11,160 HAVE. 3441 02:32:11,160 --> 02:32:13,120 BUT THE PROBLEM IS MIXED 3442 02:32:13,120 --> 02:32:16,080 SELECTION ACTIVITY MEANS 3443 02:32:16,080 --> 02:32:17,040 NEWERRANCE ARE NOT MEMBERS OF 3444 02:32:17,040 --> 02:32:18,960 VIGNETTE WORKS AND MEMBERS OF 3445 02:32:18,960 --> 02:32:26,400 MULTIPLE NETWORKS. 3446 02:32:26,400 --> 02:32:27,600 SO, WE HAVE YOU ARE RED AND BLUE 3447 02:32:27,600 --> 02:32:30,440 TO ONE OVERLAPPING NETWORK AND 3448 02:32:30,440 --> 02:32:32,560 NOW SHARING COM ON ELEMENTS OF 3449 02:32:32,560 --> 02:32:34,840 THESE MULTI FUNCTIONAL MIXED 3450 02:32:34,840 --> 02:32:37,160 SELECTIVITY NEURONS BUT IF 3451 02:32:37,160 --> 02:32:39,680 ANATOMY IS DESTINY HOW DOES IT 3452 02:32:39,680 --> 02:32:40,760 WORK? 3453 02:32:40,760 --> 02:32:42,280 THEY ACTIVATE ONE ANOTHER AND 3454 02:32:42,280 --> 02:32:43,280 CREATE A JUMP BELL OF THOUGHTS, 3455 02:32:43,280 --> 02:32:43,640 RIGHT. 3456 02:32:43,640 --> 02:32:45,080 IF I WANT TO THINK THE RED 3457 02:32:45,080 --> 02:32:46,520 THOUGHT HERE, IF I TRY TO 3458 02:32:46,520 --> 02:32:47,920 ACTIVATE A RED NEURON ACTIVITY 3459 02:32:47,920 --> 02:32:49,720 WILL TRAVEL TO OTHER RED NEURONS 3460 02:32:49,720 --> 02:32:51,960 THAT GO TO THE MIXED SELECTION 3461 02:32:51,960 --> 02:32:53,240 ACTIVITY AND MULTI FUNCTIONAL 3462 02:32:53,240 --> 02:32:55,160 NEURONS AND WE ACTIVATE THE BLUE 3463 02:32:55,160 --> 02:32:55,600 NETWORK. 3464 02:32:55,600 --> 02:32:59,160 HOW DOES YOUR BRAIN SELECT 3465 02:32:59,160 --> 02:33:01,480 INDIVIDUAL ENSEMBLES FROM THIS 3466 02:33:01,480 --> 02:33:04,160 OVERLAPPING ANATOMY WITH THESE 3467 02:33:04,160 --> 02:33:05,320 NEWERRANCE THAT SHARE COM 3468 02:33:05,320 --> 02:33:05,600 ELEMENTS. 3469 02:33:05,600 --> 02:33:15,960 THIS IS TWO ENSEMBLE. 3470 02:33:16,440 --> 02:33:19,560 ONE SOLUTION IS IT'S A NEURAL 3471 02:33:19,560 --> 02:33:23,320 OWES I WILLTATION DYNAMICS IN 3472 02:33:23,320 --> 02:33:24,280 CORTEX. 3473 02:33:24,280 --> 02:33:26,720 WE AUTOMATIC KNOW ABOUT BRAIN 3474 02:33:26,720 --> 02:33:26,920 WAVES. 3475 02:33:26,920 --> 02:33:32,000 I'LL USE IT SHORT HAND FOR NEURO 3476 02:33:32,000 --> 02:33:34,000 OSCILLATIONS AND A LARGE-SCALE 3477 02:33:34,000 --> 02:33:37,280 ORGANIZATION OF NEURAL ACTIVITY. 3478 02:33:37,280 --> 02:33:38,840 SO WHAT YOU SEE HERE IS A CROWD 3479 02:33:38,840 --> 02:33:39,720 DOING THE WAVE. 3480 02:33:39,720 --> 02:33:42,840 HERE IS THE AND FROM LEFT TO 3481 02:33:42,840 --> 02:33:46,160 RIGHT, RIGHT, THIS IS WAY FOR 3482 02:33:46,160 --> 02:33:47,560 BRAIN TO SELF-ORGANIZE ITSELF 3483 02:33:47,560 --> 02:33:49,400 AND LOOKS LIKE A CROWD CAN DO AT 3484 02:33:49,400 --> 02:33:50,400 A STADIUM. 3485 02:33:50,400 --> 02:33:52,320 BUT IN THE PAST, WHEN WE FOCUSED 3486 02:33:52,320 --> 02:33:56,040 ON SINGLE NEURONS AND WHAT THEY 3487 02:33:56,040 --> 02:33:57,680 DO, BRAIN WAVES WERE DISMISSED 3488 02:33:57,680 --> 02:33:58,960 LIKE THE HUMMING OF A CAR 3489 02:33:58,960 --> 02:33:59,560 ENGINE. 3490 02:33:59,560 --> 02:34:00,960 HUMMING REFLECTS THE ENGINE 3491 02:34:00,960 --> 02:34:03,640 RUNNING BUT IT DOESN'T MAKE THE 3492 02:34:03,640 --> 02:34:04,000 ENGINE RUN. 3493 02:34:04,000 --> 02:34:05,960 IF YOU THINK ABOUT IT, IF A 3494 02:34:05,960 --> 02:34:07,160 STADIUM CROWD CAN SELF-ORGANIZE 3495 02:34:07,160 --> 02:34:10,640 WITH THE FEW RULES, LIKE STAND 3496 02:34:10,640 --> 02:34:16,480 UP ON MY LEFT AND IS IT 3497 02:34:16,480 --> 02:34:17,400 LARGE-SCALE ORGANIZATION LIKE 3498 02:34:17,400 --> 02:34:19,360 YOU SEE HERE ISN'T THAT WHAT IS 3499 02:34:19,360 --> 02:34:21,360 NEEDED FOR TOP DOWN EXECUTIVE 3500 02:34:21,360 --> 02:34:21,720 CONTROL? 3501 02:34:21,720 --> 02:34:26,040 I MEAN, YOU KNOW, YOU CAN'T SEE 3502 02:34:26,040 --> 02:34:27,120 THESE WAVES ON INDIVIDUAL 3503 02:34:27,120 --> 02:34:29,720 NEURONS IF I MISSED AND AROUND 3504 02:34:29,720 --> 02:34:31,760 THIS CROWD AND LISTEN ONE VOICE 3505 02:34:31,760 --> 02:34:34,960 AT A TIME AND IT'S ONLY THIS 3506 02:34:34,960 --> 02:34:36,760 HIGHER LEVELS ORGANIZATION WHERE 3507 02:34:36,760 --> 02:34:37,840 WE SEE ALL THE PARTS WORKING 3508 02:34:37,840 --> 02:34:42,520 TOGETHER DO WE SEE THIS KIND OF 3509 02:34:42,520 --> 02:34:44,600 MARK RETAIL AND IT'S THE 3510 02:34:44,600 --> 02:34:46,040 ORGANIZATIONS YOU NEED FOR TOP 3511 02:34:46,040 --> 02:34:47,120 DOWN EXECUTIVE CONTROL AND IT 3512 02:34:47,120 --> 02:34:49,840 REQUIRES GETTING LARGE BITS OF 3513 02:34:49,840 --> 02:34:51,400 YOUR CORTEX OUT OF THE SAME 3514 02:34:51,400 --> 02:34:53,160 BEIGE DIRECTED TOWARDS THE TASK 3515 02:34:53,160 --> 02:34:54,480 AT HANDS. 3516 02:34:54,480 --> 02:34:57,080 AND IT'S SOMETHING CALLED 3517 02:34:57,080 --> 02:34:57,560 REPRESENTATIONAL DRIFT. 3518 02:34:57,560 --> 02:34:59,920 NEURONS ARE EXTREMELY FICKLE. 3519 02:34:59,920 --> 02:35:00,920 THEY COME AND GO. 3520 02:35:00,920 --> 02:35:02,920 IF YOU RECORD FROM 100 NEURONS 3521 02:35:02,920 --> 02:35:05,240 OR A THOUSAND NEURONS OR A 3522 02:35:05,240 --> 02:35:07,360 MILLION NEURONS AND REPEAT THE 3523 02:35:07,360 --> 02:35:09,000 SAME CONDITION 10, 20, A MILLION 3524 02:35:09,000 --> 02:35:12,320 TIMES IN A ROW, THEORETICALLY, 3525 02:35:12,320 --> 02:35:13,600 YOU WOULD GET THE DIFFERENT 3526 02:35:13,600 --> 02:35:16,080 PATTERN OF NEURONS EVERY SINGLE 3527 02:35:16,080 --> 02:35:17,160 TIME. 3528 02:35:17,160 --> 02:35:18,840 RIGHT, BECAUSE THINK OF THE 3529 02:35:18,840 --> 02:35:19,880 INDIVIDUAL NEURONS AND THE BRAIN 3530 02:35:19,880 --> 02:35:21,640 IS BEING LIKE THE WORLD'S 3531 02:35:21,640 --> 02:35:22,480 LARGEST ORCHESTRA. 3532 02:35:22,480 --> 02:35:24,880 AND THE NEURONS ARE INDIVIDUAL 3533 02:35:24,880 --> 02:35:25,600 PLAYERS. 3534 02:35:25,600 --> 02:35:27,840 BUILDING, THE ORCHESTRA IS 3535 02:35:27,840 --> 02:35:28,840 PLAYING THIS MEL BEE BUT 3536 02:35:28,840 --> 02:35:30,080 INDIVIDUAL PLAYERS COME AND GO. 3537 02:35:30,080 --> 02:35:32,120 THEY WALK IN, WALK OUT, JOIN AND 3538 02:35:32,120 --> 02:35:33,880 LEAVE THE SONG. 3539 02:35:33,880 --> 02:35:35,040 SO HOW DO YOU ORGANIZE THE 3540 02:35:35,040 --> 02:35:36,480 BRAIN? 3541 02:35:36,480 --> 02:35:38,120 HOW DO YOU PRODUCE MACRO SCOPE 3542 02:35:38,120 --> 02:35:39,280 ORGANIZATION FOR TOP DOWN 3543 02:35:39,280 --> 02:35:40,200 CONTROL ON THE LEVEL OF 3544 02:35:40,200 --> 02:35:40,880 INDIVIDUAL PLAYERS? 3545 02:35:40,880 --> 02:35:42,240 YOU CAN'T DO IT IN. 3546 02:35:42,240 --> 02:35:43,600 IT NEEDS TO BE ON THE LEVEL OF 3547 02:35:43,600 --> 02:35:49,720 THE HIGHER ORGANIZATION. 3548 02:35:49,720 --> 02:35:51,240 AND WE THERE WAS A PAPER 3549 02:35:51,240 --> 02:35:52,440 PUBLISHED RECENTLY SHOWING THAT 3550 02:35:52,440 --> 02:35:59,280 YOU CAN ACTUALLY -- I TALKED 3551 02:35:59,280 --> 02:36:01,840 ABOUT SPIKE IN LFPs AND FIVE 3552 02:36:01,840 --> 02:36:03,280 FEET OUTSIDE YOUR BRAIN BUT 3553 02:36:03,280 --> 02:36:04,320 ELECTRIC CALL FIELDS THAT 3554 02:36:04,320 --> 02:36:06,840 COMBINE ACTIVITY OF SPIKES IN 3555 02:36:06,840 --> 02:36:08,120 LFPs THAT PRODUCE MIRROR 3556 02:36:08,120 --> 02:36:10,440 ELECTRIC FIELDS THAT HOVER NEAR 3557 02:36:10,440 --> 02:36:13,360 YOUR BRAIN'S CONNECTIONS NEAR 3558 02:36:13,360 --> 02:36:15,040 ALL YOUR DENDRITES AND STUFF AND 3559 02:36:15,040 --> 02:36:16,440 WE FOUND YOU CAN READ THE 3560 02:36:16,440 --> 02:36:18,440 CONTEXT OF WORKING MEMORY, NOT 3561 02:36:18,440 --> 02:36:21,360 FROM JUST FROM THE LFPs AND 3562 02:36:21,360 --> 02:36:22,400 THE ELECTRIC FIELD LEVEL AND 3563 02:36:22,400 --> 02:36:24,400 WHAT IS COOL ABOUT THIS, IS THAT 3564 02:36:24,400 --> 02:36:26,240 THERE'S LITTLE OR NO 3565 02:36:26,240 --> 02:36:26,760 REPRESENTATIONAL DRIFT. 3566 02:36:26,760 --> 02:36:28,360 IT THIS CASE AT THIS LEVEL, YOU 3567 02:36:28,360 --> 02:36:29,760 ARE HEARING THE LONG PLAY AND 3568 02:36:29,760 --> 02:36:32,000 YOU ARE NOT GETTING THE 3569 02:36:32,000 --> 02:36:32,560 REPRESENTATIONAL DRIFT THAT 3570 02:36:32,560 --> 02:36:35,120 INDIVIDUAL PLAYERS COMING AND 3571 02:36:35,120 --> 02:36:35,680 GOING. 3572 02:36:35,680 --> 02:36:37,480 DOESN'T IT SOUND LIKE A USEFUL 3573 02:36:37,480 --> 02:36:39,240 LEVEL FOR ORGANIZING BRAIN 3574 02:36:39,240 --> 02:36:41,000 ACTIVITY AND ISN'T IT EASIER TO 3575 02:36:41,000 --> 02:36:43,280 CONTROL A STABLE REPRESENTATION 3576 02:36:43,280 --> 02:36:44,920 THAN ONE THAT FICKLE. 3577 02:36:44,920 --> 02:36:47,520 HOW DO YOU ORGANIZE THAT KIND OF 3578 02:36:47,520 --> 02:36:49,400 ACTIVITY AT LEVEL OF INDIVIDUAL 3579 02:36:49,400 --> 02:36:49,640 NEURONS. 3580 02:36:49,640 --> 02:36:52,240 AND THE VERY LEAST YOU NEED OF A 3581 02:36:52,240 --> 02:36:55,000 GAZILLION GATES ON A GAZILLION 3582 02:36:55,000 --> 02:36:56,480 SYNAPSIS NEVER MIND THE NOT 3583 02:36:56,480 --> 02:37:01,120 PROBLEM WITH THIS REPRESENT 3584 02:37:01,120 --> 02:37:02,640 REPRESENTATIONAL DRIFT. 3585 02:37:02,640 --> 02:37:04,840 SO COULD THINK ABOUT THIS, YOU 3586 02:37:04,840 --> 02:37:07,240 ORGANIZE NETWORKS BY BRAIN 3587 02:37:07,240 --> 02:37:11,720 WAVES, NEURONS THAT HUM TOGETHER 3588 02:37:11,720 --> 02:37:12,440 WATER TOGETHER. 3589 02:37:12,440 --> 02:37:14,840 AND WHAT THIS MEANS IS BRAIN A 3590 02:37:14,840 --> 02:37:19,880 MANATOMY IS NOT DESTINY BUT POSA 3591 02:37:19,880 --> 02:37:20,160 LOT. 3592 02:37:20,160 --> 02:37:21,760 IT'S MORE LIKE THE RODENT 3593 02:37:21,760 --> 02:37:23,600 HIGHWAY SYSTEM. 3594 02:37:23,600 --> 02:37:24,160 INFRASTRUCTURE. 3595 02:37:24,160 --> 02:37:26,200 IT'S SAYS WITH THE TRAFFIC THE 3596 02:37:26,200 --> 02:37:27,400 NEURAL SIGNALS OF SPIKES WHERE 3597 02:37:27,400 --> 02:37:29,200 THEY COULD GO BUT YOUR THOUGHTS 3598 02:37:29,200 --> 02:37:30,440 MOMENT TO MOMENT ARE WHERE THE 3599 02:37:30,440 --> 02:37:32,000 TRAFFIC ACTUALLY IS FLOWING FROM 3600 02:37:32,000 --> 02:37:32,760 MOMENT TO MOMENT. 3601 02:37:32,760 --> 02:37:35,040 AND THAT IS WHAT WE NEED THESE 3602 02:37:35,040 --> 02:37:36,920 BRAIN WAVE PATTERNS, THE 3603 02:37:36,920 --> 02:37:39,000 PATTERNS OF RESIDENTS DIRECTING 3604 02:37:39,000 --> 02:37:39,800 THE TRAFFIC ON THE 3605 02:37:39,800 --> 02:37:40,720 INFRASTRUCTURE OF THE YOUR 3606 02:37:40,720 --> 02:37:41,080 BRAIN. 3607 02:37:41,080 --> 02:37:43,920 AND THERE EVIDENCE FOR THIS. 3608 02:37:43,920 --> 02:37:44,280 YES. 3609 02:37:44,280 --> 02:37:45,480 NOW PLENTY. 3610 02:37:45,480 --> 02:37:47,400 AND HERE IS AN EXAMPLE OF A 3611 02:37:47,400 --> 02:37:48,920 STUDY BY TIM BUSHMAN WHEN HE WAS 3612 02:37:48,920 --> 02:37:49,800 IN MY LAB. 3613 02:37:49,800 --> 02:37:52,320 HE IS A PROFESSOR AT PRINCETON 3614 02:37:52,320 --> 02:37:53,560 AND HE HAD THE ANIMALS SWITCHED 3615 02:37:53,560 --> 02:37:54,880 BACK AND FOURTH BETWEEN TWO 3616 02:37:54,880 --> 02:37:56,240 DIFFERENT RULES AND THE ANIMAL 3617 02:37:56,240 --> 02:37:59,680 HAD THE VIEW OF VERTICAL OR 3618 02:37:59,680 --> 02:38:01,800 HORIZONTAL BAR AND THE ANIMAL 3619 02:38:01,800 --> 02:38:03,120 NEEDED TO TELL US WHAT COLOR THE 3620 02:38:03,120 --> 02:38:05,520 BAR WAS OR WHAT ITS ORIENTATION 3621 02:38:05,520 --> 02:38:07,360 WAS AND WE CUE THE ANIMAL TO 3622 02:38:07,360 --> 02:38:08,680 SWITCH BACK AND FOURTH BETWEEN 3623 02:38:08,680 --> 02:38:09,840 THESE TWO RULES. 3624 02:38:09,840 --> 02:38:11,640 WHAT IS SHOWN HERE IS IS A 3625 02:38:11,640 --> 02:38:13,760 PREFRONTAL CORTEX AND THIS IS 3626 02:38:13,760 --> 02:38:17,880 ANTERIOR, POSTERIOR, VENTRAL AND 3627 02:38:17,880 --> 02:38:19,720 DOR SAL AND ON THAT HUMAN 3628 02:38:19,720 --> 02:38:21,360 PRIMATE FANS AND EACH OF THESE 3629 02:38:21,360 --> 02:38:23,640 CIRCLES IS A RECORDING SITE AND 3630 02:38:23,640 --> 02:38:25,880 WHAT THE LINES CONNECT IS WHERE 3631 02:38:25,880 --> 02:38:27,800 WE SAW SIGNIFICANT INCREASES IN 3632 02:38:27,800 --> 02:38:30,560 APPROXIMATE LFP SYNCHRONY WHEN 3633 02:38:30,560 --> 02:38:32,400 THE ANIMAL WAS FOLLOWING THE 3634 02:38:32,400 --> 02:38:36,400 COLOR RULE AND VERSUS THE 3635 02:38:36,400 --> 02:38:39,160 ORIENTATION RULE. 3636 02:38:39,160 --> 02:38:42,960 WE LOOKED ACROSS ALL FREQUENT 3637 02:38:42,960 --> 02:38:44,600 SEN SEE. 3638 02:38:44,600 --> 02:38:46,280 WHAT WE SEE WITH THIS MODEL WITH 3639 02:38:46,280 --> 02:38:48,520 DIFFERENT PATTERNS, DIFFERENT 3640 02:38:48,520 --> 02:38:50,080 NETWORKS, FOR ONE ROLE VERSUS 3641 02:38:50,080 --> 02:38:54,080 THE OTHER ALL BASED ON THESE 3642 02:38:54,080 --> 02:38:56,160 SYNCHRONIZED LFP DYNAMICS. 3643 02:38:56,160 --> 02:38:57,960 DIFFERENT BRAIN FREQUENCIES 3644 02:38:57,960 --> 02:39:00,680 CARRY DIFFERENT TYPE OF 3645 02:39:00,680 --> 02:39:01,280 INFORMATION. 3646 02:39:01,280 --> 02:39:02,560 IN THE BACK OR FRONT OF THE 3647 02:39:02,560 --> 02:39:05,160 BRAIN THEY USE, THEY RIDE ON 3648 02:39:05,160 --> 02:39:07,400 GAMMA, HIGH FREQUENCY GAMMA 3649 02:39:07,400 --> 02:39:10,000 OSCILLATIONS BUT THE LOW 3650 02:39:10,000 --> 02:39:13,200 FREQUENCY TOP DOWN IS FILTER AND 3651 02:39:13,200 --> 02:39:15,040 REGULATE SENSORY FOSTERING THEY 3652 02:39:15,040 --> 02:39:16,240 RIDE FROM THE FRONT OF THE BRAIN 3653 02:39:16,240 --> 02:39:17,760 TO THE BACK OF THE BRAIN AND 3654 02:39:17,760 --> 02:39:20,880 THESE LOW FREQUENCY ALPHABET TA 3655 02:39:20,880 --> 02:39:22,040 OSCILLATIONS AND WE THINK IT 3656 02:39:22,040 --> 02:39:24,280 EXPLAINS THINGS LIKE THE SENSORY 3657 02:39:24,280 --> 02:39:25,120 OVERLOAD SEEN IN AUTISM AND 3658 02:39:25,120 --> 02:39:29,200 WE'RE WORKING ON METHODS AND NEW 3659 02:39:29,200 --> 02:39:33,320 TECHNOLOGY AND TO REBALANCE 3660 02:39:33,320 --> 02:39:34,120 THEM. 3661 02:39:34,120 --> 02:39:36,040 AND THESE OSCILLATIONS CAN BE 3662 02:39:36,040 --> 02:39:38,120 PRODUCED VERY PRECISE EFFECTS OF 3663 02:39:38,120 --> 02:39:43,720 CORTEX TO HERE IS A EXAMPLE. 3664 02:39:43,720 --> 02:39:49,840 IT STANDS STILL LIKE A JUMP 3665 02:39:49,840 --> 02:39:50,520 ROPE. 3666 02:39:50,520 --> 02:39:51,880 THEY DON'T BOUNCE AROUND CORTEX 3667 02:39:51,880 --> 02:39:56,920 RANDOMLY THEY TRAVEL IN SPECIFIC 3668 02:39:56,920 --> 02:39:58,480 PATTERNS AND THEY HAVE PADS AND 3669 02:39:58,480 --> 02:40:01,040 CHANGE DIRECT WITH COGNITIVE 3670 02:40:01,040 --> 02:40:02,920 DEMANDS AND THEY'RE SUPER USEFUL 3671 02:40:02,920 --> 02:40:03,960 BECAUSE THEY BUFFER INFORMATION 3672 02:40:03,960 --> 02:40:06,960 ABOUT TIME AND RECENT NETWORK 3673 02:40:06,960 --> 02:40:07,880 ACTIVITIES AND WHAT THE BRAIN 3674 02:40:07,880 --> 02:40:09,440 NEEDS TO DO COMMUTATION IF YOU 3675 02:40:09,440 --> 02:40:14,120 TAKE A VIDEO OF A POND THAT I 3676 02:40:14,120 --> 02:40:15,000 DROPPED FOUR PEBBLES UP WITH AT 3677 02:40:15,000 --> 02:40:16,200 A TIME I COULD TAKE A STILL 3678 02:40:16,200 --> 02:40:17,600 PHOTOGRAPH OF THAT VIDEO AND YOU 3679 02:40:17,600 --> 02:40:19,440 COULD TELL ME HOW MANY PEBBLES 3680 02:40:19,440 --> 02:40:20,240 HAVE DROPPED WHERE THEY DROPPED 3681 02:40:20,240 --> 02:40:22,120 AND HOW LONG AGO THEY DROPPED. 3682 02:40:22,120 --> 02:40:24,080 THAT'S HOW TRAVELING WAVES RINGS 3683 02:40:24,080 --> 02:40:24,440 THE BRAIN. 3684 02:40:24,440 --> 02:40:26,640 THERE'S A PARADIGM SHIFT IN OUR 3685 02:40:26,640 --> 02:40:31,680 UNDERSTANDING OF THE BRAIN. 3686 02:40:31,680 --> 02:40:33,440 COGNITION IS COMPLEX AND DYNAMIC 3687 02:40:33,440 --> 02:40:34,800 AND ARYTHMIC AND IT'S ORGANIZED 3688 02:40:34,800 --> 02:40:36,520 BRAIN ACTIVITY AND PLAY KEY 3689 02:40:36,520 --> 02:40:37,600 ROLES IN COGNITION ASK 3690 02:40:37,600 --> 02:40:38,760 CONSCIOUSNESS. 3691 02:40:38,760 --> 02:40:48,960 THANK YOU. 3692 02:40:52,080 --> 02:40:54,200 >>David Jones: THANK YOU, EARL. 3693 02:40:54,200 --> 02:40:56,920 I THINK I'M LOCKED OUT ON THE 3694 02:40:56,920 --> 02:40:57,280 VIDEO. 3695 02:40:57,280 --> 02:41:01,120 THANK YOU, EARL AND THAT LAYS 3696 02:41:01,120 --> 02:41:03,280 THE FOUNDATIONS GREAT FOR GOING 3697 02:41:03,280 --> 02:41:11,640 THE OTHER DIRECTION. 3698 02:41:11,640 --> 02:41:15,760 >>THANK YOU FOR THE INVITATION 3699 02:41:15,760 --> 02:41:18,560 AND LET ME GO TO A DIFFERENT 3700 02:41:18,560 --> 02:41:19,600 DIRECTION BUT I THINK THAT WE'RE 3701 02:41:19,600 --> 02:41:24,240 GOING TO CONVERGE HERE BECAUSE 3702 02:41:24,240 --> 02:41:26,960 EARL MENTIONED SOME VERY 3703 02:41:26,960 --> 02:41:28,600 FUNDAMENTAL ASPECTS OF BRAIN 3704 02:41:28,600 --> 02:41:31,040 FUNCTION. 3705 02:41:31,040 --> 02:41:33,280 HOWEVER, YEAH, I'M GOING TO GO 3706 02:41:33,280 --> 02:41:34,680 TO THE OTHER DIRECTION IN THE 3707 02:41:34,680 --> 02:41:40,320 SENSE THAT MY INTEREST IS IN 3708 02:41:40,320 --> 02:41:41,920 CLINICAL RESEARCH IN DEMENTIA 3709 02:41:41,920 --> 02:41:44,120 AND I'M GOING TO START WITH A 3710 02:41:44,120 --> 02:41:44,920 RHETORICAL QUESTION. 3711 02:41:44,920 --> 02:41:48,520 WHAT CAN WE NOT CURE ALZHEIMER'S 3712 02:41:48,520 --> 02:41:52,840 GIVEN THE FACT THAT THERE'S 3713 02:41:52,840 --> 02:41:55,800 AMPLE STUDIES THAT GO FROM THE 3714 02:41:55,800 --> 02:41:58,040 MOLECULAR SO THE CELLULAR TO THE 3715 02:41:58,040 --> 02:42:00,200 NETWORK AND THE BEHAVIORAL 3716 02:42:00,200 --> 02:42:00,840 LEVEL. 3717 02:42:00,840 --> 02:42:04,520 I'M GOING TO COME BACK TO THESE 3718 02:42:04,520 --> 02:42:05,440 QUESTIONS LATER ON. 3719 02:42:05,440 --> 02:42:09,000 THE FACT, HOWEVER, IS THAT -- 3720 02:42:09,000 --> 02:42:10,080 >>ARE YOU SHARING SLIDES 3721 02:42:10,080 --> 02:42:14,080 BECAUSE WE'RE NOT SEEING THEM. 3722 02:42:14,080 --> 02:42:15,520 >>YEAH. 3723 02:42:15,520 --> 02:42:15,920 OKAY. 3724 02:42:15,920 --> 02:42:26,240 LET ME TRY AGAIN. 3725 02:42:28,160 --> 02:42:29,200 >>LET ME TRY AGAIN. 3726 02:42:29,200 --> 02:42:30,400 >>I SEE YOUR SCREEN NOW. 3727 02:42:30,400 --> 02:42:32,760 >>OH, GOOD. 3728 02:42:32,760 --> 02:42:33,360 ALL RIGHT. 3729 02:42:33,360 --> 02:42:33,560 OKAY. 3730 02:42:33,560 --> 02:42:34,320 >>THANK YOU. 3731 02:42:34,320 --> 02:42:39,160 >>SO AT BEGINNING IT WAS A FEW 3732 02:42:39,160 --> 02:42:41,720 PLATITUDES SO COMING BACK HERE 3733 02:42:41,720 --> 02:42:44,560 CERTAINLY THE MODELING 3734 02:42:44,560 --> 02:42:47,880 APPROACHES HAVE BEEN ABLE 3735 02:42:47,880 --> 02:42:50,520 RAPIDLY AND I WOULD NOT GO NOW 3736 02:42:50,520 --> 02:42:55,280 TO THIS IS LIFE BECAUSE ACTUALLY 3737 02:42:55,280 --> 02:42:56,440 NAN TALKED ALREADY IN A SPECIAL 3738 02:42:56,440 --> 02:42:58,720 TYPE OF MODELING WHICH IS THE 3739 02:42:58,720 --> 02:43:00,960 BIOPHYSICAL CAL OR BIOLOGICALLY 3740 02:43:00,960 --> 02:43:04,440 BASED COMPETITION IN MODELS THAT 3741 02:43:04,440 --> 02:43:14,280 WE DO SIMULATIONS BASED ON BRAIN 3742 02:43:14,280 --> 02:43:15,800 ACTIVITY IN SIL I CAN OWE. 3743 02:43:15,800 --> 02:43:18,400 BASICALLY IT'S IT TO DO REVERSE 3744 02:43:18,400 --> 02:43:25,520 ENGINEERING IN THE HUMAN BRAIN 3745 02:43:25,520 --> 02:43:36,000 AND AND THIS IS WHAT I WANT TO 3746 02:43:41,840 --> 02:43:45,440 SHOW YOU NOVEL ON HOW WE 3747 02:43:45,440 --> 02:43:47,000 APPROACH THIS ISSUE. 3748 02:43:47,000 --> 02:43:49,840 SO, WE ACTUALLY HAVE BEEN 3749 02:43:49,840 --> 02:43:51,640 WORKING IN THIS KNOWN FORMAT 3750 02:43:51,640 --> 02:43:53,480 TICKS PLATFORM NOW FOR 20 YEARS, 3751 02:43:53,480 --> 02:44:02,560 NOT THAT THE PLATFORM TOOK THAT 3752 02:44:02,560 --> 02:44:13,240 LONG WH WHAT WE DO IS SIMULATE 3753 02:44:18,640 --> 02:44:20,720 NATIVE BRAIN SIGNALS. 3754 02:44:20,720 --> 02:44:26,320 THESE BRAIN SIGNALS CAN BE 3755 02:44:26,320 --> 02:44:28,560 EPILEPTIC SEIZURES YOU NAMED IT 3756 02:44:28,560 --> 02:44:30,640 AND THE IDEA IS OKAY, WHAT ARE 3757 02:44:30,640 --> 02:44:33,760 THE OPERATIONS IN THE BRAIN THAT 3758 02:44:33,760 --> 02:44:37,200 ARE GENERATING THIS BRAIN 3759 02:44:37,200 --> 02:44:38,040 SIGNALS. 3760 02:44:38,040 --> 02:44:44,000 SO WE TAKE THE DI DIMENSION 3761 02:44:44,000 --> 02:44:45,320 REDUCTION THAT IT'S THE RESULT 3762 02:44:45,320 --> 02:44:47,440 OF TWO DIFFERENT CATEGORIES OF 3763 02:44:47,440 --> 02:44:48,640 INTERACTIONS AND THE FIRST ONE 3764 02:44:48,640 --> 02:44:51,120 THAT IS THE EASIEST TO 3765 02:44:51,120 --> 02:44:53,160 UNDERSTAND IS THAT THESE SIGNALS 3766 02:44:53,160 --> 02:44:56,480 ARE GOING TO BE RELATED TO THE 3767 02:44:56,480 --> 02:45:00,960 INTERACTION, GENERATED BY THE 3768 02:45:00,960 --> 02:45:01,800 INTERACTION BETWEEN AGENTS. 3769 02:45:01,800 --> 02:45:06,080 HOW CAN WE ASSIST BIOPHYSICAL 3770 02:45:06,080 --> 02:45:07,880 PARAMETERS ASSOCIATED WITH THIS 3771 02:45:07,880 --> 02:45:08,160 INTERACTION. 3772 02:45:08,160 --> 02:45:13,160 WHAT WE DO IS WE BASED THE 3773 02:45:13,160 --> 02:45:14,800 GENERATIONAL PARAMETERS BASED ON 3774 02:45:14,800 --> 02:45:25,280 A STRUCTURAL CONNECTIVITY FROM 3775 02:45:25,280 --> 02:45:29,600 IMAGING WHEN IT'S GETS DONE AND 3776 02:45:29,600 --> 02:45:31,640 IT'S THE ONLY I AM PUT THAT WE 3777 02:45:31,640 --> 02:45:34,480 INCLUDE IN THE CALCULATIONS OF 3778 02:45:34,480 --> 02:45:37,640 BRAIN DYNAMICS SO THAT IS UP 3779 02:45:37,640 --> 02:45:39,200 WITH OF THE ASPECTS. 3780 02:45:39,200 --> 02:45:42,480 THE SECOND ONE IS IT WOULD BE 3781 02:45:42,480 --> 02:45:45,960 IDEA TO HAVE THE ABILITY LIKE 3782 02:45:45,960 --> 02:45:52,640 EARLY TO HAVE A AN ELECTRODE 3783 02:45:52,640 --> 02:45:55,680 REGARDING INDIVIDUAL AREAS WHERE 3784 02:45:55,680 --> 02:46:00,840 WE CANNOT DO THAT SO WHAT WE DO 3785 02:46:00,840 --> 02:46:04,640 IS ACTUALLY USE LOCAL MODELS 3786 02:46:04,640 --> 02:46:09,120 THAT HAVE BEEN DEVELOPED IN THE 3787 02:46:09,120 --> 02:46:10,400 LAST 200 YEARS OF NEUROSCIENCE 3788 02:46:10,400 --> 02:46:15,320 AND IT'S ASSOCIATED WITH 3789 02:46:15,320 --> 02:46:17,200 BIOPHYSICAL PARAMETERS AT THE 3790 02:46:17,200 --> 02:46:20,640 REGIONAL LEVEL SO IF WE 3791 02:46:20,640 --> 02:46:21,280 INCOMPETENT GREAT THESE TWO TYPE 3792 02:46:21,280 --> 02:46:25,560 OF ELEMENTS WE CAN SIMULATE 3793 02:46:25,560 --> 02:46:26,160 NATIVE SIGNALS. 3794 02:46:26,160 --> 02:46:27,680 HOW DO WE VALIDATE THESE 3795 02:46:27,680 --> 02:46:30,240 SIGNALS? 3796 02:46:30,240 --> 02:46:31,440 WELL, WE ARE HAVING A SOLUTION 3797 02:46:31,440 --> 02:46:35,880 FROM THE SIGNALS WE CAN SIMULATE 3798 02:46:35,880 --> 02:46:43,360 FMRIEG, MEG OR INTRA CORTICAL 3799 02:46:43,360 --> 02:46:47,520 RECORDINGS FOR EPILEPSIES FOR 3800 02:46:47,520 --> 02:46:50,080 INSTANCE AND WHO WORK AT THIS 3801 02:46:50,080 --> 02:46:52,000 LEVEL AND IN HERE I JUST HAVE A 3802 02:46:52,000 --> 02:46:56,600 REPRESENTATION OF A FUNCTIONAL 3803 02:46:56,600 --> 02:46:58,720 CONNECTOME THAT CAN BE DIFFERENT 3804 02:46:58,720 --> 02:47:01,560 REGIONS FROM SIMULATED SIGNALS 3805 02:47:01,560 --> 02:47:03,600 AND WHAT WE DO IS TO COMPARE IT 3806 02:47:03,600 --> 02:47:10,600 TO THE I AM PE SIGNALS OBTAINEDE 3807 02:47:10,600 --> 02:47:14,120 SAME INDIVIDUAL THAT HAS THE 3808 02:47:14,120 --> 02:47:14,520 DISCONNECT TOMB. 3809 02:47:14,520 --> 02:47:16,720 THESE TWO HAVE TO MATCH. 3810 02:47:16,720 --> 02:47:18,360 IF THEY DON'T MATCH WE HAVE TO 3811 02:47:18,360 --> 02:47:22,880 COME BACK TO THE MODEL TO TAKE 3812 02:47:22,880 --> 02:47:25,440 PARAMETERS UNTIL THESE TWO FIT. 3813 02:47:25,440 --> 02:47:30,400 IF THEY FIT WE HAVE A GOOD MODEL 3814 02:47:30,400 --> 02:47:36,440 AND THEM THE REVERSE AND TO SHOW 3815 02:47:36,440 --> 02:47:39,800 YOU WHAT THIS MEANS AND I'M 3816 02:47:39,800 --> 02:47:43,160 GOING TO SHOW YOU SOME RESULTS 3817 02:47:43,160 --> 02:47:46,120 ON INITIAL STUDY THAT WE CAN DO 3818 02:47:46,120 --> 02:47:49,680 AS PROOF OF CONCEPT AND ON 3819 02:47:49,680 --> 02:47:53,040 ALZHEIMER'S DISEASE SO WE HAD 3820 02:47:53,040 --> 02:47:57,800 127 NOT INDIVIDUALS AND WITH 3821 02:47:57,800 --> 02:47:59,120 COGNITIVE A ZEST MEANT 3822 02:47:59,120 --> 02:48:01,240 CATEGORIZED THEM FROM HEALTHY 3823 02:48:01,240 --> 02:48:03,960 CONTROLS AND MODERATE OR MILD 3824 02:48:03,960 --> 02:48:07,240 ALZHEIMER'S DISEASE AND WE DID 3825 02:48:07,240 --> 02:48:12,400 THIS TYPE OF MODELING AND UNDER 3826 02:48:12,400 --> 02:48:13,360 TWO DIFFERENT PARADIGMS. 3827 02:48:13,360 --> 02:48:17,040 ONE, WE DID A WHOLE BRAIN 3828 02:48:17,040 --> 02:48:21,280 MODELING AND THE SECOND WE DID 3829 02:48:21,280 --> 02:48:25,680 JUST A MODELING IN LIMERICKS OF 3830 02:48:25,680 --> 02:48:27,440 NETWORK THAT INCLUDED REGIONS 3831 02:48:27,440 --> 02:48:33,000 THAT ARE ASSOCIATED WITH THE 3832 02:48:33,000 --> 02:48:35,080 BRACK AND BRACK STAGES FOR 3833 02:48:35,080 --> 02:48:35,600 ALZHEIMER'S THAT WILL THE 3834 02:48:35,600 --> 02:48:37,440 INITIAL STAGES WENT TO THREE SO 3835 02:48:37,440 --> 02:48:40,240 INCLUDED IN NETWORK AND SIPPING 3836 02:48:40,240 --> 02:48:45,520 YOU LATE AREAS AND AND THE LIKES 3837 02:48:45,520 --> 02:48:48,200 SO WE HAVE JUST EIGHT REGIONS 3838 02:48:48,200 --> 02:48:49,680 AND EIGHT HEMISPHERE FOR THIS 3839 02:48:49,680 --> 02:48:53,240 CASE AND I TELL YOU THE PUNCH 3840 02:48:53,240 --> 02:48:57,560 LINE IS THAT THE SIMULATION THAT 3841 02:48:57,560 --> 02:49:01,400 WE COM PAINED IN THE NETWORK 3842 02:49:01,400 --> 02:49:04,040 RESULTED IN ARE SENSITIVE 3843 02:49:04,040 --> 02:49:07,200 MEASURES ON THE CHANGES THAT ARE 3844 02:49:07,200 --> 02:49:08,760 PROCURING IN THE ALZHEIMER'S 3845 02:49:08,760 --> 02:49:13,600 DISEASE AND BASICALLY, WHAT THE 3846 02:49:13,600 --> 02:49:18,520 PARAMETERS THAT CHANGE THE MOST 3847 02:49:18,520 --> 02:49:21,240 FROM CONTROLS TOEL ALZHEIMER'S 3848 02:49:21,240 --> 02:49:22,200 WERE TWO. 3849 02:49:22,200 --> 02:49:25,640 ONE, AT THE LOCAL DYNAMICAL 3850 02:49:25,640 --> 02:49:30,360 LEVEL WHERE WE SAW A REDUCTION 3851 02:49:30,360 --> 02:49:32,640 IN HIB TORI OVER COUPLING SO IN 3852 02:49:32,640 --> 02:49:37,560 ADDITION WAS DOWN LOCALLY AND WE 3853 02:49:37,560 --> 02:49:40,440 HAVE ALSO AN CHANGE IN ONE OF 3854 02:49:40,440 --> 02:49:46,280 THE PARAMETERS ASSOCIATED WITH 3855 02:49:46,280 --> 02:49:47,600 THE INTERACTIONS AND GLOBAL 3856 02:49:47,600 --> 02:49:49,240 COUPLING AND I WILL EXPLAIN THAT 3857 02:49:49,240 --> 02:49:52,080 A LITTLE BIT BETTER AND 3858 02:49:52,080 --> 02:49:54,360 BASICALLY IT'S ALMOST YOU CAN 3859 02:49:54,360 --> 02:49:57,280 SEE BY BIOLOGICALLY AND 3860 02:49:57,280 --> 02:49:58,360 EFFECTIVE OF THE BRAIN BECAUSE 3861 02:49:58,360 --> 02:50:00,480 IT CHANGES THE GAIN OF THE 3862 02:50:00,480 --> 02:50:02,320 WEIGHTS OF THE STRUCTURAL 3863 02:50:02,320 --> 02:50:03,920 CONNECTIONS SO THOSE WERE THE 3864 02:50:03,920 --> 02:50:06,880 ONES THAT CHANGED THE MOST AND 3865 02:50:06,880 --> 02:50:08,400 HOWEVER, ONE OF THE MOST 3866 02:50:08,400 --> 02:50:10,680 INTERESTING ASPECTS THAT THE 3867 02:50:10,680 --> 02:50:13,040 RESULTED IN THIS SIDE, YOU CAN 3868 02:50:13,040 --> 02:50:16,360 NOTICE HERE IN THESE FIGURES, 3869 02:50:16,360 --> 02:50:22,560 THIS IS COMPARED TO THE WHOLE 3870 02:50:22,560 --> 02:50:26,480 BRAIN SIMULATION AND THE LIMBICS 3871 02:50:26,480 --> 02:50:28,360 OF NETWORK SHOW IN TERMS OF 3872 02:50:28,360 --> 02:50:32,320 THESE TWO PARAMETERS A HIGH 3873 02:50:32,320 --> 02:50:38,160 VARIANTS SO THIS IS JUST A 3874 02:50:38,160 --> 02:50:39,400 PLATEAU JUST VARIANTS OF THE AR 3875 02:50:39,400 --> 02:50:41,960 AM TERES IF THE DIFFERENT GROUPS 3876 02:50:41,960 --> 02:50:44,320 SO FOR THE MILD COGNITIVE 3877 02:50:44,320 --> 02:50:48,000 IMPAIRMENT, POPULATION, IT WAS 3878 02:50:48,000 --> 02:50:48,360 HUGE. 3879 02:50:48,360 --> 02:50:52,240 I CAN CANNOT PUT THE POINTER ON 3880 02:50:52,240 --> 02:50:53,360 THERE BECAUSE I HAVE PICTURES 3881 02:50:53,360 --> 02:50:55,240 THERE SO HERE IS THE COUPLING TO 3882 02:50:55,240 --> 02:50:59,040 THE RIGHT IS THE COUPLING AND 3883 02:50:59,040 --> 02:51:02,320 YOU SEE THE HUGE VARIANTS. 3884 02:51:02,320 --> 02:51:04,560 NOW THESE OF COURSE 3885 02:51:04,560 --> 02:51:08,000 STATISTICALLY ANNOYING BUT 3886 02:51:08,000 --> 02:51:11,080 CLINICAL WAS TAP TAS TICK AND WE 3887 02:51:11,080 --> 02:51:16,600 KNOW THAT THIS COHORT OF MCI IS 3888 02:51:16,600 --> 02:51:17,240 HETERO GENIOUS SO SOME OF THESE 3889 02:51:17,240 --> 02:51:18,920 INDIVIDUALS ARE GOING TO CONVERT 3890 02:51:18,920 --> 02:51:21,800 TO ALZHEIMER'S AND SOME ARE 3891 02:51:21,800 --> 02:51:32,280 GOING TO SAY SO THAT WAS QUITE 3892 02:51:34,080 --> 02:51:38,800 REWARDING SO THE OTHER RESPONSE 3893 02:51:38,800 --> 02:51:41,360 TO THIS STUDY WAS THE CO 3894 02:51:41,360 --> 02:51:45,920 VARIANTS BETWEEN THE MODEL 3895 02:51:45,920 --> 02:51:48,520 METRICS AND THE COGNITION WAS 3896 02:51:48,520 --> 02:51:51,960 MUCH HIGHER THAT THE CO VARIANTS 3897 02:51:51,960 --> 02:51:53,160 WITH THE FUNCTIONSAL 3898 02:51:53,160 --> 02:51:54,440 CONNECTIVITY ASK COGNITION SO 3899 02:51:54,440 --> 02:51:58,240 WE'RE GAINING SOME KNOWLEDGE IN 3900 02:51:58,240 --> 02:52:00,640 HERE SO AFTER THIS, WHAT WE 3901 02:52:00,640 --> 02:52:06,040 WANTED DO IS TO FOLLOW-UP WAS TO 3902 02:52:06,040 --> 02:52:08,080 DETERMINE HOW THESE PARAMETERS 3903 02:52:08,080 --> 02:52:11,960 ARE CHANGING THE PHYSIOLOGY OF 3904 02:52:11,960 --> 02:52:13,200 THE SYSTEM. 3905 02:52:13,200 --> 02:52:15,320 SO FOR THIS STUDY, WHAT WE DID 3906 02:52:15,320 --> 02:52:21,760 IS FOCUSED SIMPLY OUR MODELING 3907 02:52:21,760 --> 02:52:24,520 IN THE LIMBICS NETWORK AND 3908 02:52:24,520 --> 02:52:28,400 INSTEAD OF GOING THE WHOLE WAY, 3909 02:52:28,400 --> 02:52:35,240 WE FOCUSED ON THE LOCAL FILL 3910 02:52:35,240 --> 02:52:36,800 POTENTIALS WHERE THE SIGNAL OF 3911 02:52:36,800 --> 02:52:41,400 CHOICE TO BE MODELED AS A SIGNAL 3912 02:52:41,400 --> 02:52:45,320 AND THAT WAS EVEN BY THE 3913 02:52:45,320 --> 02:52:47,320 APPROPRIATE MODEL THAT IT GIVES 3914 02:52:47,320 --> 02:52:49,520 US THE ABILITY TO SIMULATE THESE 3915 02:52:49,520 --> 02:52:51,680 TYPES OF SIGNALS. 3916 02:52:51,680 --> 02:52:55,960 AND THE SECOND CHANGE THAT WE 3917 02:52:55,960 --> 02:52:58,760 DID WAS TO DO AN ADDITIONAL 3918 02:52:58,760 --> 02:53:02,400 EXTRAIFICATION OF THE HEALTHY 3919 02:53:02,400 --> 02:53:12,840 CONTROL CASES WE KEPT THE 3920 02:53:13,360 --> 02:53:15,120 SUBJECT AROUND THE MEAN AND THE 3921 02:53:15,120 --> 02:53:17,520 SUBJECTS THAT HAD A SUPERIOR 3922 02:53:17,520 --> 02:53:19,320 PERFORMANCE AND THE IDEA OF 3923 02:53:19,320 --> 02:53:23,080 DOING THIS WAS TO HAVE SOMEHOW A 3924 02:53:23,080 --> 02:53:28,160 GOLD STANDARD IN COGNITION AND 3925 02:53:28,160 --> 02:53:30,520 WITH THE HOPE THAT WE CAN 3926 02:53:30,520 --> 02:53:33,840 DETERMINE OR DETECT DIFFERENCE 3927 02:53:33,840 --> 02:53:36,200 THIS IS BRAIN DYNAMICS BETWEEN 3928 02:53:36,200 --> 02:53:37,200 THESE TWO GROUPS. 3929 02:53:37,200 --> 02:53:47,720 I TOLD YOU THE ONLY INPUT TO THE 3930 02:54:16,240 --> 02:54:19,360 THERE WAS A TREND THAT SEPARATES 3931 02:54:19,360 --> 02:54:21,480 SOMEHOW THE NORMAL CONTROLS IN 3932 02:54:21,480 --> 02:54:24,880 BLUE VERSUS THE SUPER NORMAL IN 3933 02:54:24,880 --> 02:54:30,920 GREEN. 3934 02:54:30,920 --> 02:54:34,200 SO, AFTER THAT WE STUDIED THE 3935 02:54:34,200 --> 02:54:35,760 PHYSIOLOGY OF THE SYSTEM BECAUSE 3936 02:54:35,760 --> 02:54:39,800 WE'RE ASSUMING THAT THE SIGNALS 3937 02:54:39,800 --> 02:54:45,800 ARE BASED ON THESE TWO 3938 02:54:45,800 --> 02:54:47,280 CATEGORIES OF LOCAL DYNAMICS AND 3939 02:54:47,280 --> 02:54:51,640 WE WANTED TO UNTANGLE THESE TWO 3940 02:54:51,640 --> 02:54:57,080 COMPONENTS AND THEY ARE WORRY WE 3941 02:54:57,080 --> 02:55:05,560 DID IF UP A QUESTION WITH THE 3942 02:55:05,560 --> 02:55:09,400 VIRTUAL BRAIN AND WE HAVE BRAIN 3943 02:55:09,400 --> 02:55:10,760 SIGNALS AND I WILL NOT WILL GO 3944 02:55:10,760 --> 02:55:13,720 TO ALL THE LIMITS HERE BUT THIS 3945 02:55:13,720 --> 02:55:18,800 IS REPRESENTING THE LOCAL 3946 02:55:18,800 --> 02:55:19,760 DYNAMICS AND THE FIRST THING WE 3947 02:55:19,760 --> 02:55:24,200 DID IS TO ELIMINATE THE GLOBAL 3948 02:55:24,200 --> 02:55:27,120 DYNAMICS EX JUST TO LEAVE THE 3949 02:55:27,120 --> 02:55:37,640 DYNAMICS ALONE AND WE DIMINISH 3950 02:55:39,000 --> 02:55:45,000 THE IT TO ZERO AND THAT MEANS 3951 02:55:45,000 --> 02:55:48,000 THAT ALL THIS IS GOING TO ZERO 3952 02:55:48,000 --> 02:55:51,440 AND LEAVING US WITH A LOCAL 3953 02:55:51,440 --> 02:55:53,160 DYNAMIC AND IN ADDITION THAT AND 3954 02:55:53,160 --> 02:55:57,840 BECAUSE WE WANTED TO CAPTURE THE 3955 02:55:57,840 --> 02:55:58,520 MOST INACCEPT GENERAL 3956 02:55:58,520 --> 02:56:03,320 OSCILLATIONS WE DECREASED THESE 3957 02:56:03,320 --> 02:56:06,080 NOISE WHICH ACTUALLY REPRESENTS 3958 02:56:06,080 --> 02:56:09,720 PHYSIOLOGICAL NOISE WHICH IS 3959 02:56:09,720 --> 02:56:18,440 FASCINATING TO A MINIMUM AND WE 3960 02:56:18,440 --> 02:56:21,840 OBTAINED AND I LOVE SHOWING, 3961 02:56:21,840 --> 02:56:22,640 SIMULATED RAW SIGNALS AND YOU 3962 02:56:22,640 --> 02:56:24,000 HAVE A REP SEN STAYING OF THE 3963 02:56:24,000 --> 02:56:26,920 TIME SERIOUS ON EACH ONE OF THE 3964 02:56:26,920 --> 02:56:33,240 LIMERICKS OF THE REGIONS AND AT 3965 02:56:33,240 --> 02:56:34,520 THE BOT YOU HAVE THE SUM OF THIS 3966 02:56:34,520 --> 02:56:38,280 ACTIVITY AND YOU CAN SEE REALLY 3967 02:56:38,280 --> 02:56:42,080 RANDOM ACTIVITY THAT DOESN'T 3968 02:56:42,080 --> 02:56:43,920 PRODUCE ANY. 3969 02:56:43,920 --> 02:56:46,200 WHAT WE HAVE AFTER THAT IS THE 3970 02:56:46,200 --> 02:56:47,720 INCREASING LITTLE BY LITTLE THIS 3971 02:56:47,720 --> 02:56:52,080 VALUE OF G IN FACT THAT THEN 3972 02:56:52,080 --> 02:56:55,680 INCREASING PROGRESSIVELY THE 3973 02:56:55,680 --> 02:56:56,880 VALUE OF THE STRUCTURAL 3974 02:56:56,880 --> 02:56:58,560 CONNECTION AND FOR EACH SINGLE 3975 02:56:58,560 --> 02:57:00,560 INDIVIDUAL IT'S NOT AN IDENTICAL 3976 02:57:00,560 --> 02:57:04,320 NUMBER BUT WHAT HAPPENS IS THAT 3977 02:57:04,320 --> 02:57:10,600 THERE'S A POINT WHERE THERE'S A 3978 02:57:10,600 --> 02:57:14,800 BUY FOR INDICATION WHERE THE 3979 02:57:14,800 --> 02:57:25,360 SYSTEM CHANGES THE STATES AND IT 3980 02:57:38,680 --> 02:57:41,600 HAS BEEN PROPOSED AND NOW 3981 02:57:41,600 --> 02:57:43,240 THERE'S A LOT OF DATA THAT 3982 02:57:43,240 --> 02:57:48,280 SUPPORTS THESE AND THAT COMPLEX 3983 02:57:48,280 --> 02:57:52,200 SYSTEMS ARE WORK WHAT IS THERE'S 3984 02:57:52,200 --> 02:57:56,880 HEALTH INTO THIS THAT PRODUCES 3985 02:57:56,880 --> 02:57:59,760 THE SYSTEM TO CHANGE 3986 02:57:59,760 --> 02:58:03,840 CONFIGURATIONS IN CONNECTIVITY. 3987 02:58:03,840 --> 02:58:14,360 SO, THE OLATIONS WERE ONLY AND 3988 02:58:21,560 --> 02:58:23,720 LOW GAM HAVE REACHING IN SOME 3989 02:58:23,720 --> 02:58:26,560 CASES MUCH POORER IN OTHERS SO 3990 02:58:26,560 --> 02:58:32,120 WE STUDY THEN THIS OSCILLATIONS 3991 02:58:32,120 --> 02:58:32,720 IN THOUSANDS GROUPS. 3992 02:58:32,720 --> 02:58:35,320 IT WAS TO SEE IF THERE WAS ANY 3993 02:58:35,320 --> 02:58:38,080 CHANGES OR IN THE RELATIONSHIP 3994 02:58:38,080 --> 02:58:39,240 OF THESE FREQUENCIES GROUPS AND 3995 02:58:39,240 --> 02:58:42,800 WHAT YOU HAVE HERE, IS THAT 3996 02:58:42,800 --> 02:58:46,520 SUPER NORMALS, TWO NORMAL 3997 02:58:46,520 --> 02:58:53,080 CONTROLS TO MCI TO ALZHEIMER'S, 3998 02:58:53,080 --> 02:58:58,920 SHOW A QUADIN SUPER NORMAL 3999 02:58:58,920 --> 02:59:01,400 CONTROLS AND THAT IN SOME CASES 4000 02:59:01,400 --> 02:59:04,480 HAVE TO BEFORE THEY SAY HYPO IN 4001 02:59:04,480 --> 02:59:08,880 SOME OF THE ALZHEIMER'S CASES. 4002 02:59:08,880 --> 02:59:11,360 THIS WAS MIMIC INTO EMPIRICAL 4003 02:59:11,360 --> 02:59:14,280 RESTING ESTATE AND ALSO HAVE 4004 02:59:14,280 --> 02:59:15,960 BEEN SHOWN IN APP MALL MODELS 4005 02:59:15,960 --> 02:59:17,640 AND I'M GOING TO JUST SKIP THIS 4006 02:59:17,640 --> 02:59:21,560 BECAUSE WE DON'T HAVE TIME AND 4007 02:59:21,560 --> 02:59:28,160 IT WAS JUST THE SIGNALS. 4008 02:59:28,160 --> 02:59:30,800 AND WHAT WE SAW ALSO WAS THAT 4009 02:59:30,800 --> 02:59:35,520 THIS OSCILLATIONS CAN BE IN 4010 02:59:35,520 --> 02:59:40,440 DIFFERENT LEVELS OF THE G THAT 4011 02:59:40,440 --> 02:59:45,600 KEEP DECREASING UNTIL THEY KILLS 4012 02:59:45,600 --> 02:59:47,040 APPEAR AND THE DIFFERENCE ON 4013 02:59:47,040 --> 02:59:51,400 THIS RANGE OF Gs ALSO HAS A 4014 02:59:51,400 --> 02:59:53,280 QUADRATIC REPRESENTATION ACROSS 4015 02:59:53,280 --> 02:59:53,760 GROUPS. 4016 02:59:53,760 --> 02:59:54,880 HOWEVER THE STATE OF THE BRAIN 4017 02:59:54,880 --> 02:59:58,000 WHEN THE IMAGING IS TAKING, IS 4018 02:59:58,000 --> 03:00:01,760 KIND OF SIMILAR BETWEEN THE 4019 03:00:01,760 --> 03:00:07,240 HEALTHY CONTROLS AND IT GOES IN 4020 03:00:07,240 --> 03:00:11,160 THE CLINICAL CASES. 4021 03:00:11,160 --> 03:00:14,440 THAT MEANS THAT AN MCI AND IN 4022 03:00:14,440 --> 03:00:16,160 ALZHEIMER'S DISEASE THE SYSTEM 4023 03:00:16,160 --> 03:00:26,640 IS OPERATING FAR FROM THE BUY 4024 03:00:28,520 --> 03:00:28,960 POINT. 4025 03:00:28,960 --> 03:00:33,200 IT'S RELATED TO COGNITION AND 4026 03:00:33,200 --> 03:00:34,160 BIFURCATION -- SO IN SUMMARY 4027 03:00:34,160 --> 03:00:36,520 WHAT I TRIED TO SHOW YOU IS WE 4028 03:00:36,520 --> 03:00:39,960 HAVE OF A WAY TO HAVE A 4029 03:00:39,960 --> 03:00:45,120 MULTI-SCALE METHOD TO ASSESS THE 4030 03:00:45,120 --> 03:00:47,240 DYNAMICS AT THE LEVEL OF THE 4031 03:00:47,240 --> 03:00:48,200 WHOLE BRAIN. 4032 03:00:48,200 --> 03:00:49,520 IT'S INDIVIDUALIZED AND WE CAN 4033 03:00:49,520 --> 03:00:52,400 DO THESE MEASURES CONSTANTLY 4034 03:00:52,400 --> 03:00:56,880 BECAUSE THE DYNAMICS ARE NOT, 4035 03:00:56,880 --> 03:00:57,640 THEY'RE GOING TO BE LEARNED BUT 4036 03:00:57,640 --> 03:00:58,800 IT'S SOMETHING THAT WE'RE 4037 03:00:58,800 --> 03:01:00,560 MEASURING, IT'S TRANSLATABLE, WE 4038 03:01:00,560 --> 03:01:03,680 CAN GO TO ANIMAL MOLDS AND WE 4039 03:01:03,680 --> 03:01:07,120 CAN GET INPUT FROM ANIMAL MODELS 4040 03:01:07,120 --> 03:01:09,480 AND TO TEST IN THE MODEL AND 4041 03:01:09,480 --> 03:01:15,280 MORE IMPORTANTLY, CLINICALLY, 4042 03:01:15,280 --> 03:01:19,560 THIS APPROACH CAN PRODUCE NEW 4043 03:01:19,560 --> 03:01:23,480 HYPOTHESIS TO DESIGNED 4044 03:01:23,480 --> 03:01:25,480 INTERVENTIONS AND THE SYSTEM CAN 4045 03:01:25,480 --> 03:01:28,120 ALSO BE USED TO TRY THERAPIES 4046 03:01:28,120 --> 03:01:31,920 AND WHY, BECAUSE IF WE DEVELOP A 4047 03:01:31,920 --> 03:01:33,880 NEW THERAPY, THEN WE CAN CHANGE 4048 03:01:33,880 --> 03:01:36,400 THE PARAMETERS ASSOCIATED WITH 4049 03:01:36,400 --> 03:01:38,880 THAT THERAPY AND SEE IF THE 4050 03:01:38,880 --> 03:01:42,680 DYNAMICS OF THE BRAIN ARE 4051 03:01:42,680 --> 03:01:44,840 CHANGED. 4052 03:01:44,840 --> 03:01:47,400 I THINK THAT'S RIGHT NOW, THE 4053 03:01:47,400 --> 03:01:55,280 ISSUE OF NOT HAVING INTER 4054 03:01:55,280 --> 03:01:56,200 INTERVENTIONS FOR ALZHEIMER'S IS 4055 03:01:56,200 --> 03:01:58,000 BECAUSE WE'RE MISSING THE 4056 03:01:58,000 --> 03:02:00,720 MECHANISMS SO THAT MEANS THAT 4057 03:02:00,720 --> 03:02:06,000 THE OPPORTUNITY TO CHANGE THE 4058 03:02:06,000 --> 03:02:07,720 PARADIGM IS NOW. 4059 03:02:07,720 --> 03:02:09,640 I THINK THAT THE OPPORTUNITIES 4060 03:02:09,640 --> 03:02:13,280 ALSO, THESE TYPE OF APPROACH CAN 4061 03:02:13,280 --> 03:02:15,920 MERIT WITH OTHER OBSERVATIONS AT 4062 03:02:15,920 --> 03:02:17,680 DIFFERENT SCALES AND ALSO I 4063 03:02:17,680 --> 03:02:19,400 THINK THAT BECAUSE WE INTO 4064 03:02:19,400 --> 03:02:20,560 EVIDENCE CRITICAL MASS OF THIS 4065 03:02:20,560 --> 03:02:24,600 TYPE OF STORIES, TO MAKE A REAL 4066 03:02:24,600 --> 03:02:26,040 CHANGE, THAT ALSO THERE'S APP 4067 03:02:26,040 --> 03:02:32,440 OPPORTUNITY FOR TRAINING 4068 03:02:32,440 --> 03:02:36,600 PROGRAMS TO THIS AND OTHER 4069 03:02:36,600 --> 03:02:37,160 APPROACHES. 4070 03:02:37,160 --> 03:02:38,760 THESE ARE PEOPLE THAT ACTUALLY 4071 03:02:38,760 --> 03:02:41,000 DID THE WORK THAT I PRESENTED 4072 03:02:41,000 --> 03:02:42,280 AND THERE WE GO. 4073 03:02:42,280 --> 03:02:43,760 SORRY, ONE MINUTE LATE. 4074 03:02:43,760 --> 03:02:44,880 >>David Jones: THANK YOU, VERY 4075 03:02:44,880 --> 03:02:45,080 MUCH. 4076 03:02:45,080 --> 03:02:46,560 I BELIEVE WE'RE GOING TO TAKE A 4077 03:02:46,560 --> 03:02:48,800 10-MINUTE BREAK NOW AND COME 4078 03:02:48,800 --> 03:02:50,560 BACK AT 4:10. 4079 03:02:50,560 --> 03:02:52,720 JUST A REMINDER, QUESTIONS CAN 4080 03:02:52,720 --> 03:02:59,080 BE PUT IN THE CHAT AND WE'LL 4081 03:02:59,080 --> 03:03:00,160 ADDRESS THOSE AT THE END OF THE 4082 03:03:00,160 --> 03:03:05,640 SESSION. 4083 03:03:05,640 --> 03:03:08,440 IT'S 4:10 SO I'LL SHARE MY 4084 03:03:08,440 --> 03:03:09,120 SCREEN HERE. 4085 03:03:09,120 --> 03:03:15,800 LET ME GET STARTED. 4086 03:03:15,800 --> 03:03:22,320 SO, I'LL BE TALKING ABOUT 4087 03:03:22,320 --> 03:03:26,320 CLINICAL UTILITY AND SOME 4088 03:03:26,320 --> 03:03:27,160 DISCLOSURE TEMPERATURE 4089 03:03:27,160 --> 03:03:28,440 DISCLOSURES BUT I WILL BE 4090 03:03:28,440 --> 03:03:32,000 TALKING ABOUT OFF-LABEL USE OF 4091 03:03:32,000 --> 03:03:34,520 FDG PET A MORTALITY THAT IS 4092 03:03:34,520 --> 03:03:36,320 COMMONLY USED IN THE SETTING 4093 03:03:36,320 --> 03:03:39,040 EVALUATION OF NEURODEGENERATIVE 4094 03:03:39,040 --> 03:03:41,800 DISEASE AND COVERED AND THE 4095 03:03:41,800 --> 03:03:44,120 CURRENT FDA APPROVAL OF FDG PET 4096 03:03:44,120 --> 03:03:46,320 DOES NOT EXTEND TO THIS USE CASE 4097 03:03:46,320 --> 03:03:53,160 AND CONSIDERED OFF LABEL. 4098 03:03:53,160 --> 03:03:56,840 THIS IS THE (INAUDIBLE) TO THEIR 4099 03:03:56,840 --> 03:03:58,960 WORK IT'S A MULTI DISCIPLINE ARY 4100 03:03:58,960 --> 03:04:01,320 TEAMWORK NORTH THE CLINICAL 4101 03:04:01,320 --> 03:04:03,040 PRACTICE AND WE HAVE A LOT OF 4102 03:04:03,040 --> 03:04:13,280 SUPPORT AND PARTNERS AND BUT WE 4103 03:04:13,280 --> 03:04:15,920 VIEW OURSELVES AS AN INTER 4104 03:04:15,920 --> 03:04:17,680 DISCIPLINARY TEAMWORKING IN 4105 03:04:17,680 --> 03:04:18,960 CLINICAL DATA STREAMS THAT'S 4106 03:04:18,960 --> 03:04:21,520 SPAN THESE THREE MAJOR ZONES, 4107 03:04:21,520 --> 03:04:23,800 PEOPLE, PLACES ASK DEVICES AND 4108 03:04:23,800 --> 03:04:27,880 IT'S ZONE ONE AND WE NEED TO 4109 03:04:27,880 --> 03:04:29,320 TRANSFORM DATA AND PUT IT INTO 4110 03:04:29,320 --> 03:04:32,480 SOFTWARE AND ALGORITHMS FOR 4111 03:04:32,480 --> 03:04:34,000 COMMUTATION AND PUT THAT INTO 4112 03:04:34,000 --> 03:04:34,680 APPLICATIONS TO DELIVER THEM 4113 03:04:34,680 --> 03:04:38,360 BACK TO THE POINT OF CARE. 4114 03:04:38,360 --> 03:04:39,640 ZONE 2 CONNECTING ALL THESE 4115 03:04:39,640 --> 03:04:42,840 PEACE AND ZONE THREE WE'RE DOING 4116 03:04:42,840 --> 03:04:47,400 OUR SOFTWARE ALGORITHM BUT 4117 03:04:47,400 --> 03:04:48,720 COMPUTATIONAL NEUROLOGY, THERE'S 4118 03:04:48,720 --> 03:04:50,840 THREE MAIN ASPECTS THE WAY I 4119 03:04:50,840 --> 03:04:52,520 THINK ABOUT IT AND YOU CAN HAVE 4120 03:04:52,520 --> 03:04:56,640 A COMPUTATIONAL THR THEORETICAL 4121 03:04:56,640 --> 03:04:57,760 FRAMEWORK AND TECHNIQUES APPLIED 4122 03:04:57,760 --> 03:05:02,400 TO CLINICALLY RELEVANT NEWER 4123 03:05:02,400 --> 03:05:04,520 LOGIC DATA TEAMS AND THEORY IN 4124 03:05:04,520 --> 03:05:06,920 COMPUTATIONAL MODELS OF BRAIN 4125 03:05:06,920 --> 03:05:09,920 FUNCTIONS AND IT FOCUSES ON ONE 4126 03:05:09,920 --> 03:05:13,800 AND TWO AND THIS IS REALLY 4127 03:05:13,800 --> 03:05:15,920 GROUNDING A PRAGMATIC SCIENTIFIC 4128 03:05:15,920 --> 03:05:17,240 PROCESS FOR MENTAL FUNCTIONS AND 4129 03:05:17,240 --> 03:05:18,920 THE GOALS SHOULD BE TO PROVIDE 4130 03:05:18,920 --> 03:05:20,560 SOME FRAMEWORK TO ASK QUESTIONS 4131 03:05:20,560 --> 03:05:23,320 ABOUT CLINICALLY RELEVANT MENTAL 4132 03:05:23,320 --> 03:05:24,960 FUNCTIONS AND YOU CAN THINK OF A 4133 03:05:24,960 --> 03:05:26,400 NEUROSCIENCE FRAMEWORK OF BEING 4134 03:05:26,400 --> 03:05:28,040 MENTAL FUNCTIONS, CORRESPONDING 4135 03:05:28,040 --> 03:05:30,440 TO BIO FISCAL DYNAMICS IN THE 4136 03:05:30,440 --> 03:05:34,120 BRAIN DURING AN ORGANISMS 4137 03:05:34,120 --> 03:05:35,640 INTRINSIC INTERACTIONS AND 4138 03:05:35,640 --> 03:05:38,200 BRINGING THIS FOR ADRD IF AGING 4139 03:05:38,200 --> 03:05:41,840 YOU WOULD ALL THIS AGE RELATED 4140 03:05:41,840 --> 03:05:43,080 DEGENERATIONS OF THESE FUNCTION 4141 03:05:43,080 --> 03:05:45,040 AND THEY CORRESPOND TO FAILURES 4142 03:05:45,040 --> 03:05:46,480 IN BIOPHYSICAL DYNAMICS 4143 03:05:46,480 --> 03:05:49,680 OCCURRING IN THE BRAIN DURING AN 4144 03:05:49,680 --> 03:05:52,760 ORGANISMS INTRINSIC ASK 4145 03:05:52,760 --> 03:05:53,880 EXTRINSIC INTERACTIONS LEADING 4146 03:05:53,880 --> 03:05:54,920 TO DISABILITY. 4147 03:05:54,920 --> 03:05:56,720 BUT THERE'S VARIOUS LEVELS OF 4148 03:05:56,720 --> 03:05:57,800 ABSTRACTIONS FOR THESE 4149 03:05:57,800 --> 03:05:59,920 BIOPHYSICAL CAL DYNAMICS. 4150 03:05:59,920 --> 03:06:02,680 THOSE CAN EXIST IN GENES, 4151 03:06:02,680 --> 03:06:04,160 MOLECULES, CELLS, CIRCUITS, 4152 03:06:04,160 --> 03:06:06,760 LARGE-SCALE SYSTEMS, MENTAL 4153 03:06:06,760 --> 03:06:09,880 FUNCTIONING, AND ACTIVITIES 4154 03:06:09,880 --> 03:06:10,160 LIVING. 4155 03:06:10,160 --> 03:06:12,720 THERE WAS A RECENT ARTICLE 4156 03:06:12,720 --> 03:06:15,240 PUBLISHED LAST WEEK WHICH I 4157 03:06:15,240 --> 03:06:16,280 THINK NICELY FRAMED THESE LEVELS 4158 03:06:16,280 --> 03:06:18,800 OF ABSTRACTIONS AND DIFFERENT 4159 03:06:18,800 --> 03:06:24,080 EXPLANATORY PROJECTS ACROSS 4160 03:06:24,080 --> 03:06:26,040 THEM. 4161 03:06:26,040 --> 03:06:28,480 AND HERE YOU HEARD ABOUT 4162 03:06:28,480 --> 03:06:33,160 MECHANISTIC MODELS AND WE'LL 4163 03:06:33,160 --> 03:06:35,240 TALK ABOUT HERE MAINLY, I WANTED 4164 03:06:35,240 --> 03:06:37,840 TO PAIN ADLs ARE THE THINGS I 4165 03:06:37,840 --> 03:06:39,280 SEE IN MY CLINIC. 4166 03:06:39,280 --> 03:06:41,920 HE THINK ABOUT THESE SORT OF 4167 03:06:41,920 --> 03:06:50,520 EXPLANATORY MODELS IN DE 4168 03:06:50,520 --> 03:06:52,320 DESCRIPTIVE TERMS WITHIN THIS 4169 03:06:52,320 --> 03:06:53,440 GLOBAL FUNCTIONAL STATE SPACE 4170 03:06:53,440 --> 03:06:54,720 WHICH I WILL TELL YOU MORE ABOUT 4171 03:06:54,720 --> 03:06:57,200 THAT COINCIDES WITH WHAT YOU SAW 4172 03:06:57,200 --> 03:07:00,720 FROM EARL MILLER AND REALLY THE 4173 03:07:00,720 --> 03:07:02,520 THING I'M OBSERVING AND USING 4174 03:07:02,520 --> 03:07:04,360 ARE LARGE-SCALE PATTERNS IN THE 4175 03:07:04,360 --> 03:07:05,600 BRAIN, CALLING THESE CERTAIN 4176 03:07:05,600 --> 03:07:09,080 MODES OF FUNCTION AND YOU CAN 4177 03:07:09,080 --> 03:07:10,840 THINK OF THIS USING THE TRAFFIC 4178 03:07:10,840 --> 03:07:13,120 ANALOGY THAT EARLY USED RATHER 4179 03:07:13,120 --> 03:07:15,000 THAN THE ROADS AND STREETS, WHAT 4180 03:07:15,000 --> 03:07:17,080 YOU ALSO NEED TO PLAN YOUR TRIP 4181 03:07:17,080 --> 03:07:18,600 THROUGH NEW YORK CITY IS 4182 03:07:18,600 --> 03:07:18,840 TRAFFIC. 4183 03:07:18,840 --> 03:07:20,520 YOU NEED TO KNOW TRAFFIC AND THE 4184 03:07:20,520 --> 03:07:25,920 MODE OF THE TRAFFIC AT THE TIME. 4185 03:07:25,920 --> 03:07:27,240 SO THEY ARE GLOBAL TRAFFIC 4186 03:07:27,240 --> 03:07:31,320 PATTERNS ON TOP OF IT BRAIN 4187 03:07:31,320 --> 03:07:33,760 STRUCTURE. 4188 03:07:33,760 --> 03:07:35,720 FUL USE THESE TO ANSWER CLINICAL 4189 03:07:35,720 --> 03:07:37,640 QUESTIONS ABOUT BRAIN BEHAVIOR 4190 03:07:37,640 --> 03:07:41,600 MAP SEWING HERE IS AN EXAMPLE OF 4191 03:07:41,600 --> 03:07:42,800 WHERE, AT END OF THE TALK, WE 4192 03:07:42,800 --> 03:07:44,160 CAN UNDERSTAND HOW WE USE THESE 4193 03:07:44,160 --> 03:07:45,560 GLOBAL PATTERNS TO DESCRIBE A 4194 03:07:45,560 --> 03:07:47,760 PATIENT AND YOU CAN CLEARLY 4195 03:07:47,760 --> 03:07:49,200 SEPARATE CLINICALLY NORMAL 4196 03:07:49,200 --> 03:07:53,920 INDIVIDUALS FROM A VARIETY OF 4197 03:07:53,920 --> 03:07:57,160 DEMENTIA SYNDROMES WITH HIGH 4198 03:07:57,160 --> 03:07:58,120 ACCURACY. 4199 03:07:58,120 --> 03:08:01,240 DESCRIBING LARGE-SCALE PATTERNS, 4200 03:08:01,240 --> 03:08:03,480 THIS IS DONE IN MULTIPLE WAYS. 4201 03:08:03,480 --> 03:08:04,640 MAYBE A DECADE AGO WE THOUGHT 4202 03:08:04,640 --> 03:08:07,240 MORE ABOUT NETWORKS BUT WE SINCE 4203 03:08:07,240 --> 03:08:08,400 STARTED THINKING ABOUT MAYBE 4204 03:08:08,400 --> 03:08:10,120 THESE WEREN'T NETWORKS BUT MORE 4205 03:08:10,120 --> 03:08:11,800 CO ACTIVATION PATTERNS AND WE'RE 4206 03:08:11,800 --> 03:08:15,400 USING TERMS LIKE FUNCTIONAL 4207 03:08:15,400 --> 03:08:16,280 GRADIENTS TO DESCRIBE THESE 4208 03:08:16,280 --> 03:08:18,880 THINGS. 4209 03:08:18,880 --> 03:08:21,520 OR MORE SPACIAL TEMPORAL 4210 03:08:21,520 --> 03:08:25,280 PATTERNS AND MAYBE THEY'RE 4211 03:08:25,280 --> 03:08:25,840 PROPAGATING WAVES. 4212 03:08:25,840 --> 03:08:28,240 MORE RECENTLY SUPER POSITION OF 4213 03:08:28,240 --> 03:08:29,720 STANDING WAVES DESCRIBED THESE 4214 03:08:29,720 --> 03:08:30,800 LARGE-SCALE PATTERNS. 4215 03:08:30,800 --> 03:08:34,080 BUT HERE IS THE HISTORICAL 4216 03:08:34,080 --> 03:08:35,880 ORIGINS OF THESE PATTERNS THAT 4217 03:08:35,880 --> 03:08:37,200 ARE OBJECTS OF OBJECT 4218 03:08:37,200 --> 03:08:38,640 INVESTIGATION IN NEUROSCIENCE IT 4219 03:08:38,640 --> 03:08:41,120 COMES FROM FDG PET IN YOU GO 4220 03:08:41,120 --> 03:08:44,560 BACK TO THE PAPER FROM 1983, 4221 03:08:44,560 --> 03:08:46,240 SHOWING VERY CARE TERRIS TICK 4222 03:08:46,240 --> 03:08:52,560 PATTERN OF METABOLISM, USING FDG 4223 03:08:52,560 --> 03:08:57,440 PET, THIS IS FROM 1983 AND THEY 4224 03:08:57,440 --> 03:08:58,960 ARE EARMARKED THIS SUGGESTED THE 4225 03:08:58,960 --> 03:09:00,360 ABNORMAL FUNCTIONAL BEHAVIOR 4226 03:09:00,360 --> 03:09:02,640 THAT DEMENTIA SUBJECTED HAD 4227 03:09:02,640 --> 03:09:04,800 RELATED TO DISTURBED FUNCTIONING 4228 03:09:04,800 --> 03:09:06,200 SURVIVING TISSUE THEN TO LOSS OF 4229 03:09:06,200 --> 03:09:08,000 BRAIN SUBSTANCE ITSELF AND I 4230 03:09:08,000 --> 03:09:10,000 KNOW IT'S ALSO THIS CAN OCCUR IN 4231 03:09:10,000 --> 03:09:14,680 MY CLINIC BECAUSE OF A PATIENT 4232 03:09:14,680 --> 03:09:23,080 HAS A STROKE OR A LESION, IT 4233 03:09:23,080 --> 03:09:28,200 CHANGES DRAMATICALLY AS DOES THE 4234 03:09:28,200 --> 03:09:30,680 FUNCTION. 4235 03:09:30,680 --> 03:09:31,840 THESE PATTERNS CONTINUED TO BE 4236 03:09:31,840 --> 03:09:33,480 RECOGNIZED IN THE '90s IN 4237 03:09:33,480 --> 03:09:35,720 CLINICAL SETTINGS. 4238 03:09:35,720 --> 03:09:39,000 YOU CAN SEE MAGNITUDE IMAGES AND 4239 03:09:39,000 --> 03:09:44,080 THIS IS DISEASE SEVERITY. 4240 03:09:44,080 --> 03:09:46,880 HERE IS IS IMAGE WHERE THE 4241 03:09:46,880 --> 03:09:49,280 BRIGHT COLORS INDICATE UPTICK 4242 03:09:49,280 --> 03:09:51,080 AND THEY ARE ALWAYS NOTED THAT 4243 03:09:51,080 --> 03:09:52,800 THERE'S THIS CURIOUS 4244 03:09:52,800 --> 03:09:56,800 PRESERVATION OF PRIMARY MOTOR 4245 03:09:56,800 --> 03:09:58,160 COURT SEES IN THESE PATTERNS AND 4246 03:09:58,160 --> 03:09:59,440 THIS IS SOMETHING THAT AS USED 4247 03:09:59,440 --> 03:10:01,360 BY CLINICIANS TO IDENTIFY 4248 03:10:01,360 --> 03:10:03,400 ALZHEIMER'S PATTERNS, IT'S A 4249 03:10:03,400 --> 03:10:06,920 STRANGE PRESERVATION OF PRIMARY 4250 03:10:06,920 --> 03:10:07,200 COURT SEES. 4251 03:10:07,200 --> 03:10:09,240 THIS PATTERN IS NOW BEEN 4252 03:10:09,240 --> 03:10:12,720 OBSERVED IN FUNCTIONAL 4253 03:10:12,720 --> 03:10:16,440 CONNECTIVITY AND YOU CAN ALSO DO 4254 03:10:16,440 --> 03:10:18,280 DECOMPOSITION OF FDG AND FIND 4255 03:10:18,280 --> 03:10:20,760 THE SAME PATTERN OF DEGENERATIVE 4256 03:10:20,760 --> 03:10:21,840 DISEASES SO IT'S SOMETHING ABOUT 4257 03:10:21,840 --> 03:10:23,720 THIS LARGE-SCALE PATTERN THAT IS 4258 03:10:23,720 --> 03:10:25,120 VERY IMPORTANT FOR THE PATTERNS 4259 03:10:25,120 --> 03:10:32,760 WE OBSERVED IN THE CLINIC. 4260 03:10:32,760 --> 03:10:36,600 SOON AFTER, MARCUS RAKEEL USED 4261 03:10:36,600 --> 03:10:38,160 FDG PET THAT CERTAIN AREAS OF 4262 03:10:38,160 --> 03:10:40,400 THE BRAIN ALWAYS WERE LESS 4263 03:10:40,400 --> 03:10:41,960 METABOLICALLY ACTIVE DURING 4264 03:10:41,960 --> 03:10:44,400 CERTAIN DEMANDING TASKS AND 4265 03:10:44,400 --> 03:10:46,000 COINED THE TERM DEFAULT MODE 4266 03:10:46,000 --> 03:10:49,760 NETWORK IT WAS ACCIDENTALLY SUBY 4267 03:10:49,760 --> 03:10:52,280 IDENTIFIED BY MRI AND TASK MRI 4268 03:10:52,280 --> 03:10:54,080 AND SHOWN TO BE ABNORMAL AND 4269 03:10:54,080 --> 03:10:56,520 ALZHEIMER'S DISEASE AND SAME 4270 03:10:56,520 --> 03:10:58,320 PATTERN. 4271 03:10:58,320 --> 03:11:00,120 SO, SINCE AFTER DESCRIBING THE 4272 03:11:00,120 --> 03:11:03,800 DEFAULT MODE NETWORK, OTHER 4273 03:11:03,800 --> 03:11:04,760 NETWORKS WERE DESCRIBED AND ON 4274 03:11:04,760 --> 03:11:06,640 THE RIGHT AND LEFT EXECUTIVE 4275 03:11:06,640 --> 03:11:08,360 NETWORKS AND THESE THINGS HAVE 4276 03:11:08,360 --> 03:11:15,360 MANY NAMES AND WE'LL GET TO THAT 4277 03:11:15,360 --> 03:11:25,840 AND HERE IS ANOTHER SPACIAL 4278 03:11:32,200 --> 03:11:33,520 DESCRIPTION AND THE MULTI DEMAND 4279 03:11:33,520 --> 03:11:35,120 SYSTEM CONTRASTING THAT WITH THE 4280 03:11:35,120 --> 03:11:36,560 LANGUAGE SYSTEM IT'S IMPORTANT 4281 03:11:36,560 --> 03:11:38,400 FOR THINKING ABOUT DIS EXECUTIVE 4282 03:11:38,400 --> 03:11:39,480 FORM OF ALZHEIMER'S VERSUS 4283 03:11:39,480 --> 03:11:43,400 LANGUAGE PRESENTATIONS OF 4284 03:11:43,400 --> 03:11:45,360 ALZHEIMER'S. 4285 03:11:45,360 --> 03:11:46,840 PEOPLE USE COGNITIVE CONTROL. 4286 03:11:46,840 --> 03:11:50,840 BUT IN GENERAL, THERE'S NOT A 4287 03:11:50,840 --> 03:11:52,840 CONSENSUS IN THE FIELD FOR THESE 4288 03:11:52,840 --> 03:11:54,480 LARGE-SCALE PATTERNS. 4289 03:11:54,480 --> 03:11:55,680 WHAT EXECUTIVE FUNCTION NETWORK 4290 03:11:55,680 --> 03:11:59,240 IS THE TITLE OF THIS ARTICLE. 4291 03:11:59,240 --> 03:12:03,720 PEOPLE USE TERMS LIKE COGNITIVE 4292 03:12:03,720 --> 03:12:07,520 DORRAL, EXECUTIVE CONTROL AND OF 4293 03:12:07,520 --> 03:12:10,880 WORK BEING MEMORY NETWORKS AND 4294 03:12:10,880 --> 03:12:14,200 THE SAME SPACIAL PATTERN GIVES 4295 03:12:14,200 --> 03:12:19,120 DIFFERENT FAILS IF YOU CLUSTER 4296 03:12:19,120 --> 03:12:26,880 OVER THE PATTERNS, THERE'S FOUR. 4297 03:12:26,880 --> 03:12:28,240 WE LOOK IN ALZHEIMER'S, HERE IS 4298 03:12:28,240 --> 03:12:30,160 SIX PATIENTS THAT I SAW AND MADE 4299 03:12:30,160 --> 03:12:32,520 THESE IMAGES ON THE LEFT OF THE 4300 03:12:32,520 --> 03:12:34,840 GLUCOSE UPTICK IN THEIR BRAIN 4301 03:12:34,840 --> 03:12:40,240 AND THESE IMAGES ARE OF TAU 4302 03:12:40,240 --> 03:12:44,600 PROTEIN AND YOU SEE THERE'S A 4303 03:12:44,600 --> 03:12:45,680 CORRESPONDENCE AND THIS PATIENT 4304 03:12:45,680 --> 03:12:48,400 HAD A MEMORY PREDOMINANT 4305 03:12:48,400 --> 03:12:50,760 DISORDER AND THIS PATIENT HAD A 4306 03:12:50,760 --> 03:12:52,200 VISUAL SPACIAL PREDOMINANT DIS 4307 03:12:52,200 --> 03:12:58,280 SCORED ORDERAND THIS PATIENT HAR 4308 03:12:58,280 --> 03:12:59,680 PREDOMINANT DISORDER AND SO HERE 4309 03:12:59,680 --> 03:13:02,280 IS SIX DIFFERENT TYPES OF 4310 03:13:02,280 --> 03:13:04,080 ALZHEIMER'S DISEASE AND IT'S 4311 03:13:04,080 --> 03:13:09,920 LIKELY A SPECTRUM OR CONTINUUM 4312 03:13:09,920 --> 03:13:11,680 BAYS YOU CAN SUBTYPE THESE 4313 03:13:11,680 --> 03:13:15,360 EXECUTIVE CASES AND YOU RECENTLY 4314 03:13:15,360 --> 03:13:17,160 USED DATA DRIVEN TECHNIQUES TO 4315 03:13:17,160 --> 03:13:18,360 DEFINE OR DIFFERENT TYPES OF 4316 03:13:18,360 --> 03:13:18,800 ALZHEIMER'S. 4317 03:13:18,800 --> 03:13:20,480 THESE ARE PATIENTS I SEE IN MY 4318 03:13:20,480 --> 03:13:24,480 CLINIC AND I KNOW THEY EXIST AND 4319 03:13:24,480 --> 03:13:25,760 THEY'RE VERY DIFFERENT SYMPTOMS 4320 03:13:25,760 --> 03:13:27,360 IF THE RIGHT SIDE OF THE BRAIN 4321 03:13:27,360 --> 03:13:29,840 OR THE LEFT SIDE OF THE BRAIN IS 4322 03:13:29,840 --> 03:13:32,240 WHERE THE PROBLEM IS AND WE WERE 4323 03:13:32,240 --> 03:13:36,880 ABLE TO SHOW THIS IN A 4324 03:13:36,880 --> 03:13:39,760 DATA-DRIVEN WAY AND OF PROPOSE A 4325 03:13:39,760 --> 03:13:41,880 FRAMEWORK FOR EXECUTIVE 4326 03:13:41,880 --> 03:13:44,920 FUNCTIONING WHICH IS DIFFERENT 4327 03:13:44,920 --> 03:13:47,560 THAN THE TRADITIONAL MODEL AND 4328 03:13:47,560 --> 03:13:48,960 WE THINK IT'S HELPING US 4329 03:13:48,960 --> 03:13:50,320 UNDERSTAND OUR PATIENTS BETTER 4330 03:13:50,320 --> 03:13:53,840 IF WE THINK ABOUT IT THIS WAY. 4331 03:13:53,840 --> 03:13:57,200 THIS ARE OTHER SYNDROMES, UNTIL 4332 03:13:57,200 --> 03:13:57,840 ALZHEIMER'S. 4333 03:13:57,840 --> 03:13:59,400 THEY'RE MORE FOCAL LIKE A 4334 03:13:59,400 --> 03:14:04,640 PROGRESSIVE AUDITORY VERBAL OR 4335 03:14:04,640 --> 03:14:05,520 PEER WORD DEAFNESS WHERE THEY 4336 03:14:05,520 --> 03:14:07,000 CAN HEAR SOUNDS JUST FINE BUT 4337 03:14:07,000 --> 03:14:09,600 THEY CANNOT UNDERSTAND SPOKEN 4338 03:14:09,600 --> 03:14:10,320 VERBAL LANGUAGE. 4339 03:14:10,320 --> 03:14:14,240 AND IT'S A FOCAL LEFT SIDED GEE 4340 03:14:14,240 --> 03:14:16,000 DEN RACE AND EVIDENT IN 4341 03:14:16,000 --> 03:14:26,680 STRUCTURAL MRI AND TAU PET. 4342 03:14:26,680 --> 03:14:31,080 AND IT INFORMATION IS IN A PDG 4343 03:14:31,080 --> 03:14:31,280 PELT. 4344 03:14:31,280 --> 03:14:34,000 WE HAVE NETWORKS WHICH CAN TAKE 4345 03:14:34,000 --> 03:14:38,480 AN FDG PET AND IMPUTE A TAU PET 4346 03:14:38,480 --> 03:14:38,840 SCAN. 4347 03:14:38,840 --> 03:14:40,240 AND ONE OF THE ADVANTAGES OF TAU 4348 03:14:40,240 --> 03:14:43,520 PET IS THAT IT CAN DIFFERENTIATE 4349 03:14:43,520 --> 03:14:45,360 THAT ALZHEIMER'S SPECTRUM FROM 4350 03:14:45,360 --> 03:14:49,320 THE FRONTAL TEMPORAL SPECTRUM 4351 03:14:49,320 --> 03:14:51,080 AND PDF PET CAN DO THAT AS WELL 4352 03:14:51,080 --> 03:14:54,400 AND IT CAN SYNTHESIZE THE TAU 4353 03:14:54,400 --> 03:14:59,200 PET AND FDG PET TELLS YOU ABOUT 4354 03:14:59,200 --> 03:15:01,360 INFORMATION THAT TAU PET DOES 4355 03:15:01,360 --> 03:15:04,600 NOT. 4356 03:15:04,600 --> 03:15:08,960 AND WE DID TRY TO UNDERSTAND AND 4357 03:15:08,960 --> 03:15:10,640 IT'S LEARNING THE STRUCTURE AND 4358 03:15:10,640 --> 03:15:12,080 PRINCIPLE GRADIENT WITH THE 4359 03:15:12,080 --> 03:15:16,800 SENSORY MOTOR COREY SEE IS 4360 03:15:16,800 --> 03:15:19,680 IMPORTANT AND WITH SO DEFINITELY 4361 03:15:19,680 --> 03:15:22,040 USING GLOBAL INFORMATION AND NOT 4362 03:15:22,040 --> 03:15:32,560 LOCAL TO SYNTHESIZE THE TAU PET. 4363 03:15:32,560 --> 03:15:34,440 SO, IT TELLS YOU ABOUT OTHER 4364 03:15:34,440 --> 03:15:44,880 FORMS OF DEGENERATION AND 4365 03:15:46,200 --> 03:15:47,600 THERE'S THE CINGULAR LET ISLAND 4366 03:15:47,600 --> 03:15:48,520 SIGN AND IT'S DIFFICULT FOR 4367 03:15:48,520 --> 03:15:50,720 PEOPLE TO IDENTIFY THESE 4368 03:15:50,720 --> 03:15:52,640 PATTERNS BUT THEY'RE THERE AND 4369 03:15:52,640 --> 03:15:53,960 CONTRAST ALZHEIMER'S AND WE 4370 03:15:53,960 --> 03:15:57,520 FOUND SIMILAR PATTERNS INDICATED 4371 03:15:57,520 --> 03:16:02,080 TDP43 AND A CONDITION CALLED 4372 03:16:02,080 --> 03:16:09,480 HIPPOCAMPAL SCLEROSIS AND IT'S 4373 03:16:09,480 --> 03:16:11,160 IN THAT PET SO WE CAN IDENTIFY 4374 03:16:11,160 --> 03:16:14,200 MIXED PATTERNS WHEN YOU HAVE FDF 4375 03:16:14,200 --> 03:16:15,400 PATTERN TO LOOKS A LITTLE BIT 4376 03:16:15,400 --> 03:16:25,920 MORE DLB LIKE AND WE'RE STARTING 4377 03:16:33,080 --> 03:16:34,960 TO DO THIS AND PEOPLE WHO HAD 4378 03:16:34,960 --> 03:16:36,520 PET DURING LIFE AND THEY COME TO 4379 03:16:36,520 --> 03:16:38,960 AUTOPSY AND WE CAN STAGE THEM 4380 03:16:38,960 --> 03:16:42,000 BOTH ON ALZHEIMER'S AND 4381 03:16:42,000 --> 03:16:44,640 PATHOLOGY, BRAIN STEM LOUIE BODY 4382 03:16:44,640 --> 03:16:45,840 PATIENTS YOU WOULD NEVER CROSS 4383 03:16:45,840 --> 03:16:48,920 THE ZERO LINE WHERE'S FOLKS WHO 4384 03:16:48,920 --> 03:16:52,480 HAVE A TRANSITIONAL OR PATHOLOGY 4385 03:16:52,480 --> 03:16:54,920 ANDLY LIKELY ALZHEIMER'S DISEASE 4386 03:16:54,920 --> 03:16:56,160 ARE BELOW THE LINE VERSUS HIGH 4387 03:16:56,160 --> 03:17:05,920 SO WE THINK WE WILL DO THIS. 4388 03:17:05,920 --> 03:17:07,680 A LOT OF TIMES YOU SEE 4389 03:17:07,680 --> 03:17:08,480 STRUCTURAL CHANGES IN THE BRAIN 4390 03:17:08,480 --> 03:17:17,560 AND YOU THINK IT'S A IF IT'S 4391 03:17:17,560 --> 03:17:19,360 CONNECTED SOUL SIDE AND THE 4392 03:17:19,360 --> 03:17:21,440 LONGITUDINAL FISHER AND YOU CAN 4393 03:17:21,440 --> 03:17:23,720 SEE IN THIS EXAMPLE, THAT IS NOT 4394 03:17:23,720 --> 03:17:24,880 FOLLOWING THESE PATTERNS WE'RE 4395 03:17:24,880 --> 03:17:26,920 TALKING ABOUT AND IT'S NOT 4396 03:17:26,920 --> 03:17:30,480 LIKELY A NEURODEGENERATIVE 4397 03:17:30,480 --> 03:17:31,760 DISEASE LIKE ALZHEIMER'S AND 4398 03:17:31,760 --> 03:17:33,480 IT'S LIKELY A PROBLEM OF 4399 03:17:33,480 --> 03:17:36,040 REGULATING CSF DYNAMICS AND 4400 03:17:36,040 --> 03:17:38,080 NORMAL PRESSURE HYDROCEPHALUS 4401 03:17:38,080 --> 03:17:42,760 AND THESE PATIENTS ARE CURRENTLY 4402 03:17:42,760 --> 03:17:43,760 POORLY RECOGNIZED AND TREATED 4403 03:17:43,760 --> 03:17:45,320 AND WE NEED TO DO A BETTER JOB 4404 03:17:45,320 --> 03:17:46,280 OF CARING FOR THEM. 4405 03:17:46,280 --> 03:17:50,960 YOU CAN SEE HERE, THIS CASE AS 4406 03:17:50,960 --> 03:17:52,760 DESCRIBED AS CLEAR POCKETS OF 4407 03:17:52,760 --> 03:17:56,600 SPINAL FLUID IN THESE AREAS AND 4408 03:17:56,600 --> 03:17:59,560 FDG PET BRAIN WAS NORMAL AND WE 4409 03:17:59,560 --> 03:18:00,760 DID A SHUTTING PROCEDURE AND YOU 4410 03:18:00,760 --> 03:18:02,440 CAN SEIZE IT HERE AND THERE'S 4411 03:18:02,440 --> 03:18:03,600 CLINICAL IMPROVEMENT AND 4412 03:18:03,600 --> 03:18:11,520 STRUCTURAL IMPROVEMENT. 4413 03:18:11,520 --> 03:18:14,000 THERE'S A IMPORTANT ROLE FOR FDB 4414 03:18:14,000 --> 03:18:17,880 PET IN THE VALUATION OF 4415 03:18:17,880 --> 03:18:20,360 PATIENTS. 4416 03:18:20,360 --> 03:18:23,320 WHETHER IT'S NEUROLOGICAL, 4417 03:18:23,320 --> 03:18:25,360 DEGENERATIVE OR NPH OR IT CAN 4418 03:18:25,360 --> 03:18:27,520 TELL YOU ABOUT 80% AND SPECTRUM 4419 03:18:27,520 --> 03:18:29,280 AND THIS ALLOWS TARGETED 4420 03:18:29,280 --> 03:18:30,720 EMERGENCY AND EXISTING 4421 03:18:30,720 --> 03:18:34,080 THERAPEUTICS AND COUNSELING 4422 03:18:34,080 --> 03:18:35,040 MANAGEMENT. 4423 03:18:35,040 --> 03:18:35,880 AND CLINICAL TRIALS. 4424 03:18:35,880 --> 03:18:41,440 WE'LL BE ABLE TO DO THAT WE CAN 4425 03:18:41,440 --> 03:18:43,240 USE A SIMPLE UNDERLINING 4426 03:18:43,240 --> 03:18:45,280 PATTERNS SO HERE WE DID A 4427 03:18:45,280 --> 03:18:47,400 DIMENSIONALITY REDUCTION AND TO 4428 03:18:47,400 --> 03:18:48,520 VARIABILITY AND ALL THESE 4429 03:18:48,520 --> 03:18:49,920 DIFFERENT PATTERNS WE CAN SEE 4430 03:18:49,920 --> 03:18:53,000 AND YOU ARE ONLY NEED ABOUT 10 4431 03:18:53,000 --> 03:18:56,600 DIFFERENT PATTERNS THAT WE 4432 03:18:56,600 --> 03:18:57,800 DESCRIBE EVERYTHING I JUST WAS 4433 03:18:57,800 --> 03:19:01,040 TELLING YOU ABOUT AND NOW YOU 4434 03:19:01,040 --> 03:19:04,840 CAN DESCRIBE PATIENT SCANS RAZ A 4435 03:19:04,840 --> 03:19:06,600 COMBINATION OF THESE 10 BRAINS 4436 03:19:06,600 --> 03:19:08,000 AND CLINICAL PRACTICE AND THAT 4437 03:19:08,000 --> 03:19:10,480 WERE EVALUATING WHERE WE'RE 4438 03:19:10,480 --> 03:19:17,800 USING MORE 50 AND IT DESCRIBES 4439 03:19:17,800 --> 03:19:19,480 THESE SAME PATTERNS AS WELL AND 4440 03:19:19,480 --> 03:19:22,600 YOU CAN RELATE THEM TO COGNITIVE 4441 03:19:22,600 --> 03:19:25,480 FUNCTION AND YOU CAN RELATE THEM 4442 03:19:25,480 --> 03:19:29,120 TO NEURAL NETWORKS AND YOU CAN 4443 03:19:29,120 --> 03:19:32,680 RELATE THEM TO PATIENTS SYMPTOMS 4444 03:19:32,680 --> 03:19:33,560 AND SYNDROMES. 4445 03:19:33,560 --> 03:19:35,760 HERE WE'RE SHOWING MEAT ANALYTIC 4446 03:19:35,760 --> 03:19:36,840 FUNCTION AND PATTERNS AND YOU 4447 03:19:36,840 --> 03:19:38,520 CAN LOOK AT THEM IN THE SAME 4448 03:19:38,520 --> 03:19:40,280 FRAMEWORK THAT WE'RE LOOK AT OUR 4449 03:19:40,280 --> 03:19:44,120 PATIENT'S BRAINS AND THE 4450 03:19:44,120 --> 03:19:47,480 DISTANCE AND IT'S PREDICTIVE OF 4451 03:19:47,480 --> 03:19:51,000 THEIR CLINICAL SYNDROME AND SO 4452 03:19:51,000 --> 03:19:52,640 WE CALL THIS THE GLOBAL 4453 03:19:52,640 --> 03:19:53,440 FUNCTIONAL STATE SPACE AND IT'S 4454 03:19:53,440 --> 03:19:54,640 A DIFFERENT WAY OF THINKING 4455 03:19:54,640 --> 03:19:56,560 ABOUT THESE LARGE-SCALE BRAIN 4456 03:19:56,560 --> 03:20:00,880 PATTERNS AND THE RELATIONSHIP TO 4457 03:20:00,880 --> 03:20:11,240 BRAIN FUNCTION AND. 4458 03:20:42,680 --> 03:20:47,360 >>THERE WAS A CLEAR RELATION IF 4459 03:20:47,360 --> 03:20:55,560 WE MODEL OVER WINDOW LATE AN ANR 4460 03:20:55,560 --> 03:20:57,480 THERE WAS ONE GLOBAL PATTERN IN 4461 03:20:57,480 --> 03:20:58,080 TRANSITIONING BETWEEN THEM 4462 03:20:58,080 --> 03:21:00,120 DESCRIBES WHAT WE TRADITIONALLY 4463 03:21:00,120 --> 03:21:06,160 CALL FUNCTIONAL CONNECTIVITY AND 4464 03:21:06,160 --> 03:21:07,800 AND WE'RE ABLE TO ACTUALLY 4465 03:21:07,800 --> 03:21:09,440 MONITOR PATIENTS NOW COMPARE 4466 03:21:09,440 --> 03:21:10,600 THEIR BRAINS AND THIS FUNCTIONAL 4467 03:21:10,600 --> 03:21:12,320 STATE SPACE TO OTHER PATIENTS 4468 03:21:12,320 --> 03:21:15,400 WE'VE SEEN AND HAVE DIFFER 4469 03:21:15,400 --> 03:21:15,720 CONDITIONS. 4470 03:21:15,720 --> 03:21:17,240 WHEN THEY IMPROVE CLINICALLY 4471 03:21:17,240 --> 03:21:19,520 WITH TREATMENT WE SEE CHANGE AND 4472 03:21:19,520 --> 03:21:22,000 THEY MOVE TO A NORMAL 4473 03:21:22,000 --> 03:21:22,360 NEIGHBORHOOD. 4474 03:21:22,360 --> 03:21:24,480 WE CAN TRACK PATIENTS OVER TIME. 4475 03:21:24,480 --> 03:21:27,080 THESE ARE GENETIC FTD PATIENTS 4476 03:21:27,080 --> 03:21:29,080 AND THEY'RE DESTINED TO GET 4477 03:21:29,080 --> 03:21:30,520 FRONTAL TEMPORAL DEMENTIA AND 4478 03:21:30,520 --> 03:21:32,080 THESE BLUE AREAS ARE NORMAL 4479 03:21:32,080 --> 03:21:33,360 LOOKING BRAINS AND THIS IS OUR 4480 03:21:33,360 --> 03:21:34,520 PATIENT WHEN THEY'RE NORMAL AND 4481 03:21:34,520 --> 03:21:36,400 THEY MOVE INTO AN ABNORMAL 4482 03:21:36,400 --> 03:21:37,520 NEIGHBORHOOD AND THAT CHANGE 4483 03:21:37,520 --> 03:21:39,400 ACTUALLY OCCURS BEFORE SYMPTOMS 4484 03:21:39,400 --> 03:21:44,000 ONSET AND WE CAN TRACK THAT VERY 4485 03:21:44,000 --> 03:21:46,000 PRECISELY BY MOVEMENT FROM THE 4486 03:21:46,000 --> 03:21:56,360 SPACE AND THIS SPACE. 4487 03:23:09,040 --> 03:23:12,200 >>SO THAT MEANS YOU LIKELY HAVE 4488 03:23:12,200 --> 03:23:14,560 LOUIE BIO DISEASE AS WELL. 4489 03:23:14,560 --> 03:23:16,000 SO THIS CHANGES FROM A 4490 03:23:16,000 --> 03:23:17,400 DISCONNECT PER A DIME TO A 4491 03:23:17,400 --> 03:23:19,200 POPULATION DYNAMICS PARADIGM AND 4492 03:23:19,200 --> 03:23:21,240 BOTH ACCOUNT FOR THESE 4493 03:23:21,240 --> 03:23:24,360 LARGE-SCALE BRAIN PATTERNS BUT 4494 03:23:24,360 --> 03:23:26,840 THEY HAVE DIFFERENT MECHANISTIC 4495 03:23:26,840 --> 03:23:28,760 EXPLANATION AND DEGENERATIVE 4496 03:23:28,760 --> 03:23:31,200 LARGE-SCALE BRAIN DYNAMICS YOU 4497 03:23:31,200 --> 03:23:33,800 WANT TO CONTROL JUST TO CHANGE 4498 03:23:33,800 --> 03:23:36,960 THESE THINGS. 4499 03:23:36,960 --> 03:23:39,960 SO, SOME SUGGESTIONS HERE IS 4500 03:23:39,960 --> 03:23:41,440 THAT WE HAVE THIS INFRASTRUCTURE 4501 03:23:41,440 --> 03:23:43,560 THAT CAN SUPPORT MEASURING, 4502 03:23:43,560 --> 03:23:46,880 MODELING AND INTERVENING ON 4503 03:23:46,880 --> 03:23:48,520 LARGE-SCALE BRAIN DYNAMICS AND 4504 03:23:48,520 --> 03:23:50,680 MENTAL FUNCTIONS AND SO THANK 4505 03:23:50,680 --> 03:23:52,120 YOU FOR YOUR ATTENTION AND I 4506 03:23:52,120 --> 03:23:53,520 KNOW I'M GOING OVER A LITTLE BIT 4507 03:23:53,520 --> 03:23:59,080 ON TIME. 4508 03:23:59,080 --> 03:24:01,120 AND I'LL TURN IT OVER TO DANI 4509 03:24:01,120 --> 03:24:04,040 BASSETT WHO WILL TALK ABOUT WAYS 4510 03:24:04,040 --> 03:24:05,680 NETWORK CONTROL RELATES TO BRAIN 4511 03:24:05,680 --> 03:24:14,800 METABOLISM. 4512 03:24:14,800 --> 03:24:15,960 THANK YOU SO MUCH MANY OF IT'S 4513 03:24:15,960 --> 03:24:16,720 SO GREAT TO BE HERE. 4514 03:24:16,720 --> 03:24:18,400 I WOULD LIKE TO GIVE MY THOUGHTS 4515 03:24:18,400 --> 03:24:19,880 OVER THE NEXT FEW MINUTES ABOUT 4516 03:24:19,880 --> 03:24:21,400 USING NETWORK CONTROL THEORY TO 4517 03:24:21,400 --> 03:24:24,360 MODEL THENNENNER JET TICKS OF 4518 03:24:24,360 --> 03:24:25,720 BRAIN FUNCTION AND I APOLOGIZE 4519 03:24:25,720 --> 03:24:26,480 FOR MY THROAT. 4520 03:24:26,480 --> 03:24:28,880 I'M GETTING OVER COVID. 4521 03:24:28,880 --> 03:24:31,200 SO, THE FUNCTION OF MANY 4522 03:24:31,200 --> 03:24:31,920 BIOLOGICAL SYSTEMS IS MADE 4523 03:24:31,920 --> 03:24:33,680 POSSIBLE BY A NETWORK ALONG 4524 03:24:33,680 --> 03:24:35,600 WHICH ITEMS OF INTEREST LIKE 4525 03:24:35,600 --> 03:24:42,240 NUTRIENTS, GOODS AND INFORMATION 4526 03:24:42,240 --> 03:24:44,320 IT'S COMPOSED OF REGIONS THAT 4527 03:24:44,320 --> 03:24:46,200 PERFORM SPECIFIC FUNCTIONS AND 4528 03:24:46,200 --> 03:24:49,080 ENGAGE IN PARTICULAR 4529 03:24:49,080 --> 03:24:51,320 COMMUTATIONS AND AND THOSE 4530 03:24:51,320 --> 03:24:54,920 REGIONS ARE CONNECTED AND OUR 4531 03:24:54,920 --> 03:24:56,600 LARGE-SCALE TRUCKS AND IT'S A 4532 03:24:56,600 --> 03:25:01,160 BUNDLE OF AXONS ALONG WHICH 4533 03:25:01,160 --> 03:25:06,360 INFORMATION BEARING THEY HAVE A 4534 03:25:06,360 --> 03:25:09,680 PATTERN OF CONNECTIVITY THAT 4535 03:25:09,680 --> 03:25:12,880 CONSTRAISTRAINS HAS FOCUSED ON A 4536 03:25:12,880 --> 03:25:18,040 VARIETY OF STATISTICAL MEASURES 4537 03:25:18,040 --> 03:25:20,040 CHARACTERIZE THAT PATTERNS OF 4538 03:25:20,040 --> 03:25:21,640 CONNECTIVE AND HOW IT CON 4539 03:25:21,640 --> 03:25:22,640 STRAINS THE PASSAGE OF 4540 03:25:22,640 --> 03:25:23,320 INFORMATION. 4541 03:25:23,320 --> 03:25:24,200 THEY RANGE FROM SOMETHING LIKE 4542 03:25:24,200 --> 03:25:27,520 THE CLUSTERING CO EFFICIENT AND 4543 03:25:27,520 --> 03:25:29,560 THE NUMBER OF TRY AGES AND THE 4544 03:25:29,560 --> 03:25:31,440 NUMBER OF CONNECTED TRIPLES TO 4545 03:25:31,440 --> 03:25:32,600 THE HUB ORGANIZATION AND THE 4546 03:25:32,600 --> 03:25:34,760 PRESENCE OF CAVITIES AND 4547 03:25:34,760 --> 03:25:36,400 SHORTCUTS AND MODULAR TEE OR 4548 03:25:36,400 --> 03:25:37,360 COMMUNITY STRUCTURE. 4549 03:25:37,360 --> 03:25:39,520 BUT IN EACH CASE, THE GOAL IS TO 4550 03:25:39,520 --> 03:25:41,240 UNDERSTAND HOW THAT PATTERN CON 4551 03:25:41,240 --> 03:25:44,000 STRAINS WHERE INFORMATION CAN 4552 03:25:44,000 --> 03:25:44,440 FLOW. 4553 03:25:44,440 --> 03:25:47,200 IN TURN, THAT PATTERN OF 4554 03:25:47,200 --> 03:25:48,000 INFORMATION FLOW DETERMINES THE 4555 03:25:48,000 --> 03:25:49,360 SORTS OF FUNCTIONS THAT THE 4556 03:25:49,360 --> 03:25:52,080 BRAIN CAN SUPPORT AND THEREFORE 4557 03:25:52,080 --> 03:25:55,920 UNDERSTANDING THE STRUCTURAL 4558 03:25:55,920 --> 03:25:59,640 NETWORK CONSTRAINTS OF THE BRAIN 4559 03:25:59,640 --> 03:26:03,040 AND IT'S ALTERATION DISEASE. 4560 03:26:03,040 --> 03:26:04,440 THEY HAVE EXPANDED THE 4561 03:26:04,440 --> 03:26:06,920 INVESTIGATION OF STRUCTURAL 4562 03:26:06,920 --> 03:26:08,200 CONSTRAINTS IN SEVERAL WAYS. 4563 03:26:08,200 --> 03:26:10,480 FIRST THE FIELD HAS SEEN AN 4564 03:26:10,480 --> 03:26:12,760 INCREASE IN THE SENSITIVITY OF 4565 03:26:12,760 --> 03:26:13,840 MEASUREMENTS AND SO TYPICALLY 4566 03:26:13,840 --> 03:26:16,840 WHAT IS USED FOR HUMANS IS 4567 03:26:16,840 --> 03:26:18,160 DIFFERENT FUSION WEIGHTED MRI 4568 03:26:18,160 --> 03:26:20,440 AND IT'S SENSITIVE TO MICRO 4569 03:26:20,440 --> 03:26:22,240 STRUCTURAL INTEGRITY AND 4570 03:26:22,240 --> 03:26:23,960 PROVIDES TRACK LOCATION AT FINER 4571 03:26:23,960 --> 03:26:25,880 AND FINER SPACIAL RESOLUTIONS. 4572 03:26:25,880 --> 03:26:28,040 THAT IS MADE POSSIBLE BY 4573 03:26:28,040 --> 03:26:29,360 INCREASED SCAN TONE, BY AN 4574 03:26:29,360 --> 03:26:31,280 INCREASING NUMBER OF DIFFUSION 4575 03:26:31,280 --> 03:26:35,720 DIRECTIONS AND EXTENSIONS ON THE 4576 03:26:35,720 --> 03:26:39,760 ALGORITHMIC SIDE OF THE CO NOT 4577 03:26:39,760 --> 03:26:40,280 YOUTATIONAL. 4578 03:26:40,280 --> 03:26:41,600 WE SEE THE BRAIN IN A MUCH 4579 03:26:41,600 --> 03:26:42,200 RICHER WAY. 4580 03:26:42,200 --> 03:26:43,880 IN ADDITION TO THESE 4581 03:26:43,880 --> 03:26:44,920 INCREASINGLY SENSITIVE 4582 03:26:44,920 --> 03:26:45,840 MEASUREMENTS THERE'S BEEN A 4583 03:26:45,840 --> 03:26:49,520 FOCUS ON DEVELOPING DATA 4584 03:26:49,520 --> 03:26:51,680 INFORMED COMPUTATIONAL MODEL 4585 03:26:51,680 --> 03:26:55,880 THAT ALLOW US TO INVESTIGATE 4586 03:26:55,880 --> 03:27:04,000 THEM DIFFERENTLY REPERTOIRE AND 4587 03:27:04,000 --> 03:27:06,120 ONE EXAMPLE OF SUCH A DATA 4588 03:27:06,120 --> 03:27:07,920 INFORMED COMPUTATIONAL MODEL IS 4589 03:27:07,920 --> 03:27:09,840 THE NETWORK CONTROL MODEL. 4590 03:27:09,840 --> 03:27:20,360 IT HAS PROVEN PARTICULARLY AIR 4591 03:27:26,800 --> 03:27:28,200 TRAFFIC CONTROL SYSTEMS AND 4592 03:27:28,200 --> 03:27:29,880 ROBOTICS AND THE IDEA OF NETWORK 4593 03:27:29,880 --> 03:27:32,280 CONTROL THEORY IS THAT WE HAVE A 4594 03:27:32,280 --> 03:27:34,760 NETWORK DYNAMICAL SYSTEM AND 4595 03:27:34,760 --> 03:27:37,520 HERE THAT IS SHOWN AS A TOY 4596 03:27:37,520 --> 03:27:39,960 EXAMPLE OF A NETWORK OF FOUR 4597 03:27:39,960 --> 03:27:41,160 NODES AND FOUR EDGES IN ADDITION 4598 03:27:41,160 --> 03:27:43,640 TO HAVING THAT NETWORK, WE ALSO 4599 03:27:43,640 --> 03:27:45,400 HAVE INPUT INTO THE SYSTEM FOR 4600 03:27:45,400 --> 03:27:52,640 THE BRAIN THAT SORT OF THING AND 4601 03:27:52,640 --> 03:27:55,280 INPUT HERE WE SEE AN INPUT INTO 4602 03:27:55,280 --> 03:27:57,920 X1, X2, AND WITH THOSE INPUTS 4603 03:27:57,920 --> 03:28:00,480 WHICH CAN VARY OVER TIME, THE 4604 03:28:00,480 --> 03:28:02,560 STATE OF THE SYSTEM CAN CHANGE. 4605 03:28:02,560 --> 03:28:04,080 SO INITIALLY PERHAPS THIS SYSTEM 4606 03:28:04,080 --> 03:28:06,480 IS SITTING AT THE ORIGIN WHERE 4607 03:28:06,480 --> 03:28:07,160 EACH OF THE NODES HAS AN 4608 03:28:07,160 --> 03:28:09,440 ACTIVITY LEVEL OF ZERO AND THEN 4609 03:28:09,440 --> 03:28:11,800 AFTER THESE INPUTS HAVE BEEN 4610 03:28:11,800 --> 03:28:13,000 INJECTED, THE STATE OF THE 4611 03:28:13,000 --> 03:28:15,360 SYSTEM IS MOVED TO A DIFFERENT 4612 03:28:15,360 --> 03:28:17,840 STATE, A DIFFERENT PLACE ON THE 4613 03:28:17,840 --> 03:28:18,680 STATE SPACE. 4614 03:28:18,680 --> 03:28:20,640 WHAT NETWORK CONTROL IS WHAT 4615 03:28:20,640 --> 03:28:22,400 SORT OF INPUTS CAN DRIVE THE 4616 03:28:22,400 --> 03:28:23,960 SYSTEM FROM SOME INITIAL STATE 4617 03:28:23,960 --> 03:28:25,360 OF TO SOME FINAL STATE AND WHAT 4618 03:28:25,360 --> 03:28:27,040 SORTS OF FINAL STATES ARE 4619 03:28:27,040 --> 03:28:29,040 POSSIBLE TO GOAT AND HOW. 4620 03:28:29,040 --> 03:28:31,760 NOW THE NETWORK CONTROL MODEL 4621 03:28:31,760 --> 03:28:33,800 STIMULATES PRECISELY HOW 4622 03:28:33,800 --> 03:28:35,760 ACTIVITY FLOWS ALONG STRUCTURAL 4623 03:28:35,760 --> 03:28:36,240 CONNECTIONS. 4624 03:28:36,240 --> 03:28:38,480 AND IT IS MADE POSSIBLE BY 4625 03:28:38,480 --> 03:28:40,280 DEFINING THE DYNAMICS OF THE 4626 03:28:40,280 --> 03:28:41,680 SYSTEM ACCORDING TO WHERE THE 4627 03:28:41,680 --> 03:28:43,280 STRUCTURAL CONSTRAINTS ARE. 4628 03:28:43,280 --> 03:28:44,920 THAT MODEL CAN HAVE VARYING 4629 03:28:44,920 --> 03:28:47,080 LEVELS OF COMPLEXITY BUT HERE IS 4630 03:28:47,080 --> 03:28:48,000 A SIMPLE ONE. 4631 03:28:48,000 --> 03:28:50,640 THE STATE OF THE BRAIN X AT TIME 4632 03:28:50,640 --> 03:28:52,040 T PLUS 1 IS EQUAL TO THE STATE 4633 03:28:52,040 --> 03:28:54,920 OF THE BRAIN AT TIME T TIMES SUM 4634 03:28:54,920 --> 03:28:56,680 PATTERN OF CONNECTIVITY WHICH IS 4635 03:28:56,680 --> 03:29:02,080 TYPICALLY THIS WEIGHTED AND WE 4636 03:29:02,080 --> 03:29:05,840 CAN DERIVE WHERE USE OF CAP APP 4637 03:29:05,840 --> 03:29:08,320 IS THE INPUT INJECTED INTO KAPPA 4638 03:29:08,320 --> 03:29:10,840 REGIONS AT TIME T AND IT'S A 4639 03:29:10,840 --> 03:29:12,840 MATRIX AND WITH ONES ALONG THE 4640 03:29:12,840 --> 03:29:16,800 SIGNAL AND WHERE THE INPUT IS 4641 03:29:16,800 --> 03:29:26,960 HERE AND. 4642 03:29:42,480 --> 03:29:44,400 >>AS PATTERNS OF ACTIVITY 4643 03:29:44,400 --> 03:29:46,480 ACROSS NEURAL UNITS AND THE 4644 03:29:46,480 --> 03:29:48,480 PATTERNS OF ACTIVITY CAN 4645 03:29:48,480 --> 03:29:49,320 REPRESENTS EVENTS OR OUR 4646 03:29:49,320 --> 03:29:51,600 EXPERIENCES OR CONSULTS AND 4647 03:29:51,600 --> 03:29:53,320 IMPORTANTLY, WE MOVE FROM ONE 4648 03:29:53,320 --> 03:29:55,160 STATE OF ACTIVITY TO ANOTHER IN 4649 03:29:55,160 --> 03:29:58,680 A WAY THAT TAKESSENNER GAO HE 4650 03:29:58,680 --> 03:30:00,120 AND THEN GEAR GEE IT TAKES TO 4651 03:30:00,120 --> 03:30:02,120 MOVE FROM ONE STATE TO ANOTHER 4652 03:30:02,120 --> 03:30:03,640 DEPENDS ON HOW ACTIVITY WITH 4653 03:30:03,640 --> 03:30:04,720 FLOW THROUGH THIS SYSTEM. 4654 03:30:04,720 --> 03:30:07,280 IT DEPENDS ON THE STRUCTURAL 4655 03:30:07,280 --> 03:30:07,960 CONSTRAINTS. 4656 03:30:07,960 --> 03:30:09,560 AND WHEN WE THINK ABOUT STATE 4657 03:30:09,560 --> 03:30:10,640 TRANSITIONS, WE NEED TO THINK 4658 03:30:10,640 --> 03:30:12,320 ABOUT NOT JUST THE PATTERNS OF 4659 03:30:12,320 --> 03:30:13,480 ACTIVATION THAT WE OPEN BUT ALSO 4660 03:30:13,480 --> 03:30:15,240 THE NETWORK UNDERNEATH OF IT AND 4661 03:30:15,240 --> 03:30:17,720 WE KNOW THAT ACTIVE NEURONS CAN 4662 03:30:17,720 --> 03:30:21,680 SPREAD ACTIVITY TO OTHER 4663 03:30:21,680 --> 03:30:22,480 NEWERRANCE AROUND THEM AND IT'S 4664 03:30:22,480 --> 03:30:24,680 EASIER IF THAT ARE CONNECTED. 4665 03:30:24,680 --> 03:30:27,720 THIS ALLOWS US TO THINK OF 4666 03:30:27,720 --> 03:30:29,640 THROUGH WHAT SORT ARE EASY 4667 03:30:29,640 --> 03:30:31,040 VERSUS DIFFICULT AND SO HERE FOR 4668 03:30:31,040 --> 03:30:32,640 EXAMPLE IF WE HAD A BRAIN, THAT 4669 03:30:32,640 --> 03:30:34,560 HAD A PATTERN OF CONNECTIVITY 4670 03:30:34,560 --> 03:30:36,440 LIKE THIS VERY MODULAR NETWORK 4671 03:30:36,440 --> 03:30:39,440 WITH ONE SET OF FIVE NODES BEING 4672 03:30:39,440 --> 03:30:40,560 INTERCONNECTED WITH ONE ANOTHER 4673 03:30:40,560 --> 03:30:42,800 AND ANOTHER SET WITH ONE ANOTHER 4674 03:30:42,800 --> 03:30:45,280 AND YOU WE WANT TO HAVE AN 4675 03:30:45,280 --> 03:30:46,240 ACTIVITY STATE WHERE THE FIRST 4676 03:30:46,240 --> 03:30:47,880 FIVE UNITS ARE ACTIVE AND THE 4677 03:30:47,880 --> 03:30:49,440 SECOND FIVE UNITS ARE NOT 4678 03:30:49,440 --> 03:30:50,720 PARTICULARLY ACTIVE THIS 4679 03:30:50,720 --> 03:30:53,280 COMBINATION IS PRETTY EASY TO 4680 03:30:53,280 --> 03:30:54,480 ATTAIN AND MAINTAIN AND THE 4681 03:30:54,480 --> 03:30:56,160 REASON IS THAT THIS ACTIVATION 4682 03:30:56,160 --> 03:30:58,920 STATE CAN CAPITALIZE ON THE 4683 03:30:58,920 --> 03:31:00,080 UNDERLYING NETWORK STRUCTURAL 4684 03:31:00,080 --> 03:31:02,320 AND SO WE JUST NEED AN EXCITE 4685 03:31:02,320 --> 03:31:03,640 TORI SIGNAL TO BE INJECTED INTO 4686 03:31:03,640 --> 03:31:05,400 THE FIRST MODULE AND INHIBITORY 4687 03:31:05,400 --> 03:31:09,560 SIGNAL IN THE SECOND MODULE AND 4688 03:31:09,560 --> 03:31:10,760 BECAUSE THERE'S ONLY ONE WEAK 4689 03:31:10,760 --> 03:31:11,880 LINE BETWEEN THEM THE ACTIVITY 4690 03:31:11,880 --> 03:31:14,200 CAN BE ISOLATED ACROSS THE TWO 4691 03:31:14,200 --> 03:31:15,920 MODELS SUCH AS THE ACTIVE ONE 4692 03:31:15,920 --> 03:31:19,320 DOESN'T ACTIVATE THE I INACTIVE 4693 03:31:19,320 --> 03:31:19,960 ONE. 4694 03:31:19,960 --> 03:31:30,320 HERE IS AN EXAMPLE OF. 4695 03:31:46,040 --> 03:31:48,560 >>YOU HAVE TO WORK UNDER THE 4696 03:31:48,560 --> 03:31:50,760 UNDERLYING STRUCTURE IN ORDER TO 4697 03:31:50,760 --> 03:31:52,480 REACH THIS ACTIVATION STATE. 4698 03:31:52,480 --> 03:31:53,760 HERE IS THE LAST EXAMPLE WHERE 4699 03:31:53,760 --> 03:31:55,320 WE HAVE THE MODULAR NETWORK 4700 03:31:55,320 --> 03:31:56,480 AGAIN WITH ONLY ONE CONNECTION 4701 03:31:56,480 --> 03:31:58,040 BETWEEN THE TWO MODULES AND THE 4702 03:31:58,040 --> 03:31:59,600 STATE THAT WE WANT TO GET TO IS 4703 03:31:59,600 --> 03:32:00,880 WHERE THE FIRST UNIT IS ACTING 4704 03:32:00,880 --> 03:32:05,120 AND THE SECOND UNIT IS NOT 4705 03:32:05,120 --> 03:32:15,320 ACTIVE AND. 4706 03:32:19,200 --> 03:32:20,760 >>IT HELPS US TO THINK ABOUT 4707 03:32:20,760 --> 03:32:22,280 WHICH STATE TRANSITIONS ARE EASY 4708 03:32:22,280 --> 03:32:22,960 VERSUS DIFFICULT. 4709 03:32:22,960 --> 03:32:24,160 NOT JUST WHICH STATES ARE EASY 4710 03:32:24,160 --> 03:32:25,080 TO GET TO. 4711 03:32:25,080 --> 03:32:27,120 SO, HERE IS AN EASY STATE 4712 03:32:27,120 --> 03:32:27,840 TRANSITION. 4713 03:32:27,840 --> 03:32:29,160 HERE WE HAVE ACTIVATION OF THE 4714 03:32:29,160 --> 03:32:30,560 FIRST FIVE DEACTIVATION OF THE 4715 03:32:30,560 --> 03:32:31,880 SECOND AND WE WANT TO SWITCH IT 4716 03:32:31,880 --> 03:32:33,640 SO THE FIRST FIVE ARE INACTIVE 4717 03:32:33,640 --> 03:32:35,720 AND THE SECOND FIVE ARE ACTIVE. 4718 03:32:35,720 --> 03:32:40,520 TO DO THIS ON THIS MODULAR 4719 03:32:40,520 --> 03:32:42,320 ACTIVE AND EXCITE TORI CONTROL 4720 03:32:42,320 --> 03:32:43,960 SIGNAL INTO THE SECOND MODULE SO 4721 03:32:43,960 --> 03:32:46,560 WE ONLY REALLY NEED TWO GENERIC 4722 03:32:46,560 --> 03:32:47,280 CONTROL SIGNALS. 4723 03:32:47,280 --> 03:32:49,520 IF CONTRAST IF WE WANT TO ENACT 4724 03:32:49,520 --> 03:32:50,960 THE STATE TRANSITION I'M SHOWING 4725 03:32:50,960 --> 03:32:53,080 59 BOTTOM WE NEED A LOT MORE. 4726 03:32:53,080 --> 03:32:54,760 SO, HERE WE HAVE THE MODULAR 4727 03:32:54,760 --> 03:32:56,520 NETWORK AGAIN AND THE STATE THAT 4728 03:32:56,520 --> 03:33:00,080 WE WANT TO START WITH, IS THIS 4729 03:33:00,080 --> 03:33:02,520 ON AND 06 BINARY STATE AND WE 4730 03:33:02,520 --> 03:33:04,240 WILL SWITCH IT THAT ANYTHING ON 4731 03:33:04,240 --> 03:33:06,200 IS OFF AND ANYTHING THAT WAS 4732 03:33:06,200 --> 03:33:07,800 OFFS IS NOW ON. 4733 03:33:07,800 --> 03:33:09,360 TO ENACT THIS STATE TRANSITION, 4734 03:33:09,360 --> 03:33:11,280 WE NEED TO INJECT EITHER AN 4735 03:33:11,280 --> 03:33:12,800 EXCITE TORI CONTROL SIGNAL AND 4736 03:33:12,800 --> 03:33:14,360 AGAIN INTO EVERY SINGLE NODE IN 4737 03:33:14,360 --> 03:33:15,320 THE NETWORK. 4738 03:33:15,320 --> 03:33:17,480 SO WHEN I SAY THAT A STATE 4739 03:33:17,480 --> 03:33:27,920 TRANSITION IS EASY, MANY. 4740 03:33:53,960 --> 03:33:57,400 >>THE BRAIN MAY MOVE ALONG THIS 4741 03:33:57,400 --> 03:33:59,360 TRAJECTORY FROM X TO SOME 4742 03:33:59,360 --> 03:34:05,800 MODELED GRAY SCALE IMAGE XT IN 4743 03:34:05,800 --> 03:34:07,880 CONTRAST TO MOVE TO SOME FINAL 4744 03:34:07,880 --> 03:34:10,520 STATE XT COLORED IN ROYAL PURPLE 4745 03:34:10,520 --> 03:34:13,120 HERE ACTIVATION OF THE VORTEX 4746 03:34:13,120 --> 03:34:16,120 AND WHAT SORTS OF INPUTS YOU 4747 03:34:16,120 --> 03:34:17,160 INJECT NOD WHICH REGIONS AND 4748 03:34:17,160 --> 03:34:20,600 WILL ALLOW THIS TRANSITION TO 4749 03:34:20,600 --> 03:34:31,120 OCCUR ASK IT LAWS US TO AND WE 4750 03:34:32,960 --> 03:34:34,800 HAVE A COST FUNCTION THAT TEN 4751 03:34:34,800 --> 03:34:36,560 ALLIESES WHAT IS REQUIRED AND 4752 03:34:36,560 --> 03:34:38,440 THE DISTANCE OF THE CURRENT 4753 03:34:38,440 --> 03:34:40,240 STATE XT FROM THE TARGET STATE 4754 03:34:40,240 --> 03:34:42,040 SO THIS IS THE MINIMIZATION 4755 03:34:42,040 --> 03:34:43,720 WE'RE USING AND WE USE ENERGY IS 4756 03:34:43,720 --> 03:34:45,920 TO MODEL THE FACT THAT THE BRAIN 4757 03:34:45,920 --> 03:34:48,880 IS UNDER MARKED BIOLOGICAL 4758 03:34:48,880 --> 03:34:50,280 CONSTRAINTS AND WE MINIMIZE 4759 03:34:50,280 --> 03:34:52,320 DISTANCE IS IT ALLOWS FOR A 4760 03:34:52,320 --> 03:34:54,120 RELATIVELY STRAIGHT TRAJECTORY 4761 03:34:54,120 --> 03:34:55,040 FROM AN NATIONAL STATE TO A 4762 03:34:55,040 --> 03:34:55,920 FINAL STATE RATHER THAN ALLOWING 4763 03:34:55,920 --> 03:34:58,480 THE BRAIN TO NEANDER ACROSS THE 4764 03:34:58,480 --> 03:34:59,160 STATE SPACE? 4765 03:34:59,160 --> 03:35:07,360 A WAY THAT IS INEFFICIENT. 4766 03:35:07,360 --> 03:35:14,040 SO, IT'S BEEN HAPPENING AND 4767 03:35:14,040 --> 03:35:16,200 ALSO, AN INCREASE IN FOCUS ON 4768 03:35:16,200 --> 03:35:19,480 THE DEVELOPMENT OF DATA INFORMED 4769 03:35:19,480 --> 03:35:20,080 COMPUTATIONAL MODELS. 4770 03:35:20,080 --> 03:35:22,320 I RAISED NETWORK CONTROL THEORY 4771 03:35:22,320 --> 03:35:24,240 AS ONE OF THOSE COMPUTATIONAL 4772 03:35:24,240 --> 03:35:25,080 MODELS OF INTEREST. 4773 03:35:25,080 --> 03:35:27,320 THE THIRD AND FINAL REASON THAT 4774 03:35:27,320 --> 03:35:28,920 RECENT EFFORTS HAVE EXPANDED THE 4775 03:35:28,920 --> 03:35:32,760 INVESTIGATION OF STRUCTURAL 4776 03:35:32,760 --> 03:35:35,360 CONSTRAINTS, IS A SHIFT IN OUR 4777 03:35:35,360 --> 03:35:37,840 EXPLANATIONS FOR COGNITION. 4778 03:35:37,840 --> 03:35:40,000 SO, FOR A LONG PERIOD OF TIME, 4779 03:35:40,000 --> 03:35:41,440 WE HAVE MADE OF SIGNIFICANT 4780 03:35:41,440 --> 03:35:43,040 PROGRESS IN THE FIELD MANY BY 4781 03:35:43,040 --> 03:35:45,560 PROVIDING AND EXCAVATING AND 4782 03:35:45,560 --> 03:35:47,840 REPORTING ACTIVITY-BASED 4783 03:35:47,840 --> 03:35:48,800 EXPLANATIONS FOR COGNITION. 4784 03:35:48,800 --> 03:35:50,600 SO, A CERTAIN KIND OF COGNITION 4785 03:35:50,600 --> 03:35:52,480 OR COGNITIVE PROCESS IS 4786 03:35:52,480 --> 03:35:54,280 EXPLAINED BY THE PATTERN OF 4787 03:35:54,280 --> 03:35:56,680 ACTIVATION THAT WE OBSERVE ON 4788 03:35:56,680 --> 03:35:57,520 THE BRAIN. 4789 03:35:57,520 --> 03:36:01,120 NOW, IN MORE RECENT YEARS, WE'RE 4790 03:36:01,120 --> 03:36:05,360 ALSO PROVIDING AND STUDYING A 4791 03:36:05,360 --> 03:36:05,880 COMPLIMENTARY TYPE OF 4792 03:36:05,880 --> 03:36:08,240 EXPLANATION WHICH IS A STRUCTURE 4793 03:36:08,240 --> 03:36:09,920 BASED EXPLANATION AND SO IN THAT 4794 03:36:09,920 --> 03:36:12,040 KIND OF STRUCTURE BASED 4795 03:36:12,040 --> 03:36:13,080 EXPLANATION, WE ARE SUGGESTING 4796 03:36:13,080 --> 03:36:19,240 THAT A DI DYNAMICAL PROCESS THAT 4797 03:36:19,240 --> 03:36:20,240 CONNECTS THE REGIONS INVOLVED 4798 03:36:20,240 --> 03:36:21,560 AND THEREFORE THE COGNITIVE 4799 03:36:21,560 --> 03:36:23,040 PROCESS IS NOT ONLY EXPLAINED BY 4800 03:36:23,040 --> 03:36:24,840 THE PATTERN OF ACTIVATION, BUT 4801 03:36:24,840 --> 03:36:26,480 ALSO BY THE RELATION BETWEEN 4802 03:36:26,480 --> 03:36:28,880 THAT PATTERN AND THE PATTERN OF 4803 03:36:28,880 --> 03:36:32,800 CONNECTIVITY UNDERNEATH. 4804 03:36:32,800 --> 03:36:34,480 TOGETHER, THESE THREING 4805 03:36:34,480 --> 03:36:36,760 EXPANSIONS OF MEASUREMENT, 4806 03:36:36,760 --> 03:36:38,760 MODELING AND CONCEPTUAL 4807 03:36:38,760 --> 03:36:40,120 APPROACHES ARE PROVIDING A 4808 03:36:40,120 --> 03:36:41,160 RICHER UNDERSTANDING OF 4809 03:36:41,160 --> 03:36:42,560 STRUCTURAL CONSTRAINTS ON HUMAN 4810 03:36:42,560 --> 03:36:43,200 BRAIN FUNCTION. 4811 03:36:43,200 --> 03:36:45,280 NOW I WANT TO PROVIDE YOU WITH 4812 03:36:45,280 --> 03:36:47,400 AN EXAMPLE OF THAT FINAL 4813 03:36:47,400 --> 03:36:48,640 CONCEPTUAL EXPANSION AND TO DO 4814 03:36:48,640 --> 03:36:52,320 THAT I'M GOING TO FOCUS ON 4815 03:36:52,320 --> 03:36:53,840 COGNITIVE EFFORT TO INDICATE THE 4816 03:36:53,840 --> 03:36:55,040 PREPORTION OF THE LIMITED 4817 03:36:55,040 --> 03:36:56,720 CAPACITY CENTRAL PROCESSING. 4818 03:36:56,720 --> 03:36:59,080 WE KNOW FROM PREVIOUS WORK THAT 4819 03:36:59,080 --> 03:37:00,360 COGNITIVE EFFORTS IS CORRELATED 4820 03:37:00,360 --> 03:37:01,800 WITH TASK DIFFICULTY AND TASK 4821 03:37:01,800 --> 03:37:02,640 KNOWLEDGE HE HAVE TEE AND 4822 03:37:02,640 --> 03:37:05,440 VARIETY OF INDIVIDUAL FACTORS 4823 03:37:05,440 --> 03:37:07,080 INCLUDING AGE AND NEURAL 4824 03:37:07,080 --> 03:37:08,960 DIFFERENCES HOWEVER WE ALSO KNOW 4825 03:37:08,960 --> 03:37:10,600 THAT COGNITIVE EFFORT IS NOT 4826 03:37:10,600 --> 03:37:13,880 IDENTICAL WITH THE VARIABLES SO 4827 03:37:13,880 --> 03:37:14,800 THE INTERESTING QUESTION FOR US 4828 03:37:14,800 --> 03:37:17,200 IS HOW CAN ONE MEASURE COGNITIVE 4829 03:37:17,200 --> 03:37:18,240 EFFORTS. 4830 03:37:18,240 --> 03:37:20,600 A FEW COMMON MEASUREMENTS 4831 03:37:20,600 --> 03:37:21,720 INCLUDE SELF-REPORT SO YOU CAN 4832 03:37:21,720 --> 03:37:24,080 ASK THE PATIENT HOW EFFORTFUL 4833 03:37:24,080 --> 03:37:28,840 DID THAT FEEL AND YOU CAN USE 4834 03:37:28,840 --> 03:37:39,400 AUTO KNOT I CAN RESPONSE OUTPUT 4835 03:37:42,720 --> 03:37:44,440 INCA DATING MORE COGNITIVE 4836 03:37:44,440 --> 03:37:45,040 EFFORT. 4837 03:37:45,040 --> 03:37:46,240 THERE ARE INTERESTING STUDIES 4838 03:37:46,240 --> 03:37:48,000 THAT HAVE USED DYNAMICAL 4839 03:37:48,000 --> 03:37:51,040 COMPLEXITY OF THE ACTIVITY TIME 4840 03:37:51,040 --> 03:37:52,800 SERIES TO EXPLAIN COGNITIVE 4841 03:37:52,800 --> 03:37:53,000 EFFORTS. 4842 03:37:53,000 --> 03:37:54,680 WHAT I'D LIKE TO SUGGEST IN THE 4843 03:37:54,680 --> 03:37:56,600 CONTEXT OF MY PREVIOUS REMARKS, 4844 03:37:56,600 --> 03:38:02,040 IS AN ALTERNATIVE APPROACH TO 4845 03:38:02,040 --> 03:38:04,560 STUDY THE COST OF ORCHESTRATING 4846 03:38:04,560 --> 03:38:07,160 COMPLEX IDENTITY DYNAMICS ON A 4847 03:38:07,160 --> 03:38:08,960 NETWORK AS OPERATIONALIZED BY 4848 03:38:08,960 --> 03:38:10,400 NETWORK CONTROL THEORY AND 4849 03:38:10,400 --> 03:38:12,880 SPECIFICALLY BY THE CONTROL 4850 03:38:12,880 --> 03:38:13,480 ENERGY ESTIMATE. 4851 03:38:13,480 --> 03:38:15,560 TO GIVE YOU EXAMPLES OF HOW THIS 4852 03:38:15,560 --> 03:38:18,640 WORKS, I WANTED TO SHOW YOU WORK 4853 03:38:18,640 --> 03:38:20,040 FROM A VISITING FELLOW IN THE 4854 03:38:20,040 --> 03:38:20,200 LAB. 4855 03:38:20,200 --> 03:38:23,400 HE WAS REALLY INTERESTED IN 4856 03:38:23,400 --> 03:38:25,440 ASKING HOW MUCH CONTROL ENERGY 4857 03:38:25,440 --> 03:38:27,680 REQUIRED TO TRANSITION FROM APP 4858 03:38:27,680 --> 03:38:31,680 ATTENTION DEMANDING STATE TO A 4859 03:38:31,680 --> 03:38:33,360 WORKING MEMORY STATE THAT 4860 03:38:33,360 --> 03:38:35,000 REQUIRES MORE COMMENTS OF EFFORT 4861 03:38:35,000 --> 03:38:36,680 AND HOW MUCH HOLDS EITHER OF 4862 03:38:36,680 --> 03:38:37,520 THOSE STATES. 4863 03:38:37,520 --> 03:38:40,600 TO ADDRESS THOSE TWO QUESTIONS, 4864 03:38:40,600 --> 03:38:42,400 HE GATHERED STRUCTURAL 4865 03:38:42,400 --> 03:38:43,320 CONNECTIVITY DATA FROM 4866 03:38:43,320 --> 03:38:46,600 INDIVIDUAL PARTICIPANTS AND THEN 4867 03:38:46,600 --> 03:38:48,280 ALSO FUNCTIONAL MAGNETIC IMAGING 4868 03:38:48,280 --> 03:38:50,680 DATA AS THE PARTICIPANTS WERE 4869 03:38:50,680 --> 03:38:52,000 PERFORMING AS THE TASK AND A TWO 4870 03:38:52,000 --> 03:38:54,040 BACK WORKING MEMORY TASK IN THE 4871 03:38:54,040 --> 03:38:54,320 SCANNER. 4872 03:38:54,320 --> 03:38:57,520 HE APPLIED A GENERAL LINEAR 4873 03:38:57,520 --> 03:38:59,840 MODEL TO EXTRACT A BETA RATES 4874 03:38:59,840 --> 03:39:01,880 WITH THE ACTIVATIONS THAT ARE 4875 03:39:01,880 --> 03:39:02,960 CHARACTERISTIC FOR THAT PERSON 4876 03:39:02,960 --> 03:39:04,480 FOR THEIR TIME IN THE ZERO BACK 4877 03:39:04,480 --> 03:39:08,440 TASK OR THEIR TIME IN THE TIER 4878 03:39:08,440 --> 03:39:08,920 BACK TASK. 4879 03:39:08,920 --> 03:39:11,080 HE WANTEDDED TO UNDERSTAND HOW 4880 03:39:11,080 --> 03:39:12,360 MUCH ENERGY IS REQUIRED TO GET 4881 03:39:12,360 --> 03:39:13,840 FROM THIS ZERO BACK TO THE TWO 4882 03:39:13,840 --> 03:39:15,440 BACK AND GIVEN THE PATTERN OF 4883 03:39:15,440 --> 03:39:17,560 STRUCTURAL CONNECTIVITY OF THAT 4884 03:39:17,560 --> 03:39:18,320 INDIVIDUAL. 4885 03:39:18,320 --> 03:39:20,120 NOW WE KNOW THAT PRECISE CONTROL 4886 03:39:20,120 --> 03:39:22,920 OF STATE TRANSITIONS AND STATE 4887 03:39:22,920 --> 03:39:24,360 PERSISTENCE IS REQUIRED FOR 4888 03:39:24,360 --> 03:39:26,240 OPTIMAL PERFORMANCE OF THIS TASK 4889 03:39:26,240 --> 03:39:28,560 INCLUDING TASK ACCURACY AND 4890 03:39:28,560 --> 03:39:28,960 SPEED. 4891 03:39:28,960 --> 03:39:30,120 SO HERE IS THE FIRST PIECE OF 4892 03:39:30,120 --> 03:39:31,880 DATA THAT I WANTED TO SHOW YOU, 4893 03:39:31,880 --> 03:39:33,800 STUDYING TRANSITIONING TO THE 4894 03:39:33,800 --> 03:39:35,280 WORKING MORE DEMANDING WORKING 4895 03:39:35,280 --> 03:39:36,800 MEMORY STATE AND ALSO BACK DOWN 4896 03:39:36,800 --> 03:39:40,280 TO THE ZERO BACK STATE ALONG THE 4897 03:39:40,280 --> 03:39:42,440 Y AXIS HERE IS IS THE CONTROL 4898 03:39:42,440 --> 03:39:44,680 ENERGY AND ALONG THE X AXIS AN 4899 03:39:44,680 --> 03:39:48,520 INDICATING THE TRANSITION OF 4900 03:39:48,520 --> 03:39:49,760 CENTER AND MERE WE'RE MOVING 4901 03:39:49,760 --> 03:39:51,160 FROM ZERO BACK TO THE TWO BACK 4902 03:39:51,160 --> 03:39:53,280 WORKING MEMORY STATE AND YOU SEE 4903 03:39:53,280 --> 03:39:55,040 A MARKED DEGREE OF CONTROL 4904 03:39:55,040 --> 03:39:57,040 ENERGY AND BY CONTRAST, THE 4905 03:39:57,040 --> 03:39:57,880 TRANSITION FROM THE CREDIT BACK 4906 03:39:57,880 --> 03:39:59,640 STATE TO THE ZERO BACK STATE 4907 03:39:59,640 --> 03:40:01,560 REQUIRES LESS CONTROL ENERGY AND 4908 03:40:01,560 --> 03:40:03,440 SO WHAT THAT MEANS, IS THAT 4909 03:40:03,440 --> 03:40:04,880 TRANSITIONING INTO THE CON NA 4910 03:40:04,880 --> 03:40:06,400 ACTIVELY MORE DEMANDING STATE 4911 03:40:06,400 --> 03:40:07,840 REQUIRES MORE CONTROL ENERGY 4912 03:40:07,840 --> 03:40:09,640 THAN THE OPPOSITE TRANSITION. 4913 03:40:09,640 --> 03:40:11,080 THAT IS CONSISTENT WITH OUR 4914 03:40:11,080 --> 03:40:12,760 NOTIONS OF COGNITIVE EFFORTS 4915 03:40:12,760 --> 03:40:13,680 SUGGESTING THAT CONTROL ENERGY 4916 03:40:13,680 --> 03:40:18,360 MAY BE A MARKER OF COGNITIVE 4917 03:40:18,360 --> 03:40:21,040 EFFORT. 4918 03:40:21,040 --> 03:40:22,960 HOW MUCH IS HOLD ONE OF THESE 4919 03:40:22,960 --> 03:40:33,520 ESTATES AND THE ZERO BACK WE'LL 4920 03:40:36,640 --> 03:40:38,000 ASK HOW MUCH ENERGY IS REQUIRED 4921 03:40:38,000 --> 03:40:39,200 TO STAY THERE. 4922 03:40:39,200 --> 03:40:41,560 NOW WE KNOWS THAT HOLDING A 4923 03:40:41,560 --> 03:40:42,920 PARTICULAR STATE FOR A COMPLEX 4924 03:40:42,920 --> 03:40:47,440 SYSTEM WILL DEMAND ENERGY AND AS 4925 03:40:47,440 --> 03:40:54,840 LONG AS YOU ARE SEEING THE 4926 03:40:54,840 --> 03:40:56,040 CONTROL ENERGY AND WE SEE THE 4927 03:40:56,040 --> 03:40:58,160 ZERO BACK STATE IS SIGNIFICANTLY 4928 03:40:58,160 --> 03:41:04,360 MORE STABLE THAN TWO BACK STATE 4929 03:41:04,360 --> 03:41:14,800 AND THIGHS CONTROL THEORY 4930 03:41:23,920 --> 03:41:26,480 MEASURES ARE BEHAVIORALLY 4931 03:41:26,480 --> 03:41:31,760 RELEVANT AND HELPS US TO 4932 03:41:31,760 --> 03:41:32,960 UNDERSTAND THE PARTICIPANTS SO 4933 03:41:32,960 --> 03:41:43,520 IN SUMMARY WHAT WE'VE DONE IS TO 4934 03:41:44,400 --> 03:41:45,640 HOW IT FLOWS THROUGH THE SYSTEM 4935 03:41:45,640 --> 03:41:47,680 AND INFLUENCING THE TYPES OF 4936 03:41:47,680 --> 03:41:48,880 COMMUTATIONS AND FUNCTIONS THAT 4937 03:41:48,880 --> 03:41:51,720 CAN BE PERFORMED. 4938 03:41:51,720 --> 03:41:53,240 I NOTE THAT RECENT EFFORTS HAVE 4939 03:41:53,240 --> 03:41:54,560 EXPANDED THE INVESTIGATION OF 4940 03:41:54,560 --> 03:41:56,320 THESE STRUCTURAL CONSTRAINTS IN 4941 03:41:56,320 --> 03:41:57,760 THREE WAYS. 4942 03:41:57,760 --> 03:41:58,920 FIRST, BUSINESS NOT INCREASING 4943 03:41:58,920 --> 03:42:00,680 USING INCREASINGLY SENSITIVE 4944 03:42:00,680 --> 03:42:03,240 MEASUREMENTS SO EXPANDING 4945 03:42:03,240 --> 03:42:04,600 DIFFUSION WEIGHTED IMAGES FOR 4946 03:42:04,600 --> 03:42:06,280 DIRECTIONS, LONGER SCAN TIMES 4947 03:42:06,280 --> 03:42:08,280 AND MORE SOPHISTICATED 4948 03:42:08,280 --> 03:42:10,640 ALGORITHMS OF RECONSTRUCTION. 4949 03:42:10,640 --> 03:42:12,760 SECOND, THERE'S CONCERTED EFFORT 4950 03:42:12,760 --> 03:42:14,080 TO HE CAN PANNED ON THE 4951 03:42:14,080 --> 03:42:15,480 DEVELOPMENT OF DATA INFORMED 4952 03:42:15,480 --> 03:42:17,160 COMPUTATIONAL MODELS AND I 4953 03:42:17,160 --> 03:42:18,200 MENTIONED NETWORK CONTROL THEORY 4954 03:42:18,200 --> 03:42:20,000 AS A MODEL THAT I'M EXCITED 4955 03:42:20,000 --> 03:42:21,920 ABOUT AND THAT I THINK IS 4956 03:42:21,920 --> 03:42:22,960 RELEVANT AND IMPORTANT IN 4957 03:42:22,960 --> 03:42:26,440 THINKING THROUGH THESE 4958 03:42:26,440 --> 03:42:28,160 STRUCTURAL CONSTRAINTS ON 4959 03:42:28,160 --> 03:42:29,240 ACTIVATION STATES AND THEIR 4960 03:42:29,240 --> 03:42:32,280 TRANSITION. 4961 03:42:32,280 --> 03:42:35,880 THE THIRD CONSTRAINTS IS A 4962 03:42:35,880 --> 03:42:37,080 CONCEPTUAL ONE AND IT'S WHERE 4963 03:42:37,080 --> 03:42:39,600 THE FIELD IS EMBRACING A 4964 03:42:39,600 --> 03:42:41,400 CONCEPTUAL SHIFT IN EXPLANATIONS 4965 03:42:41,400 --> 03:42:42,920 FOR COGNITION FROM 4966 03:42:42,920 --> 03:42:43,760 ACTIVITY-BASED EXPLANATIONS 4967 03:42:43,760 --> 03:42:45,640 SOLELY TO A COMBINATION OF 4968 03:42:45,640 --> 03:42:47,160 ACTIVITY BASED AND STRUCTURE 4969 03:42:47,160 --> 03:42:51,760 BASED EXPLANATIONS. 4970 03:42:51,760 --> 03:42:53,400 TOGETHER, THESE THREE SORTS OF 4971 03:42:53,400 --> 03:42:59,720 EFFORTS IN MODELING AND ON HUMAN 4972 03:42:59,720 --> 03:43:01,040 BRAIN FUNCTION. 4973 03:43:01,040 --> 03:43:03,120 I CLOSE THE TALK BY FOCUSING ON 4974 03:43:03,120 --> 03:43:05,680 AN EXAMPLE WHICH WAS THE STUDY 4975 03:43:05,680 --> 03:43:11,600 OF COGNITIVE EFFORT AND 4976 03:43:11,600 --> 03:43:12,800 ILLUSTRATED COGNITIVE 4977 03:43:12,800 --> 03:43:15,120 COMMUTATIONS WITHIN A FORMAL 4978 03:43:15,120 --> 03:43:17,480 THEORY OF NETWORKENNER JET TICKS 4979 03:43:17,480 --> 03:43:19,280 SO WITH THAT THANK YOU FOR 4980 03:43:19,280 --> 03:43:20,120 LISTENING. 4981 03:43:20,120 --> 03:43:28,120 I'LL STOP SHARING. 4982 03:43:28,120 --> 03:43:28,880 >>David Jones: THAT'S GREAT. 4983 03:43:28,880 --> 03:43:29,640 THANK YOU SO MUCH. 4984 03:43:29,640 --> 03:43:32,160 I THINK WE'RE GOING TO TAKE A 4985 03:43:32,160 --> 03:43:41,880 BREAK NOW AND RETURN AT 5:00 4986 03:43:41,880 --> 03:43:43,840 >>THERE HAVE BEEN A COUPLE 4987 03:43:43,840 --> 03:43:45,400 QUESTIONS IN THE VIDEO CAST OR 4988 03:43:45,400 --> 03:43:52,560 THE CHAT SO I CAN START THERE. 4989 03:43:52,560 --> 03:43:59,560 SO, Dr. COLLINS DO YOU WANT TO 4990 03:43:59,560 --> 03:44:01,840 ASK JURY QUESTION FOR PROFESSOR 4991 03:44:01,840 --> 03:44:02,120 BASSETT IF. 4992 03:44:02,120 --> 03:44:02,400 >>SURE. 4993 03:44:02,400 --> 03:44:09,560 THANK YOU FOR THE GREAT TALKS. 4994 03:44:09,560 --> 03:44:10,880 AND I WAS INTERESTING IF YOUR 4995 03:44:10,880 --> 03:44:12,800 TALK I WAS CURIOUS WHETHER, AS 4996 03:44:12,800 --> 03:44:15,120 YOU SAID, IT WAS A VERY BIG 4997 03:44:15,120 --> 03:44:16,800 ABILITY ACROSS PARTICIPANTS AND 4998 03:44:16,800 --> 03:44:20,800 SO I'M WONDERING HOW HOW USEFUL 4999 03:44:20,800 --> 03:44:23,280 THE SIGNAL IS TOLL MEASURE 5000 03:44:23,280 --> 03:44:25,400 COGNITIVE AND WHETHER IT'S NOISY 5001 03:44:25,400 --> 03:44:27,560 AND COMPARES TO THE VARIOUS THAT 5002 03:44:27,560 --> 03:44:30,160 YOU MIGHT KEPT WITH SIMPLE 5003 03:44:30,160 --> 03:44:34,200 MEASURES LIKE SELF-REPORT OR 5004 03:44:34,200 --> 03:44:42,280 OTHER NON BRAIN IMAGING DEPEND 5005 03:44:42,280 --> 03:44:42,960 DEPENDENT MEASURES. 5006 03:44:42,960 --> 03:44:48,360 >>IT WAS ENERGY THE ENERGY 5007 03:44:48,360 --> 03:44:50,120 REQUIRED FOR A STATE TRANSITIONS 5008 03:44:50,120 --> 03:44:52,520 TO COGNITIVE AND COGNITIVELY 5009 03:44:52,520 --> 03:44:56,400 DEMANDING TASK BUT THEN ALSO TO 5010 03:44:56,400 --> 03:44:57,360 EVALUATE THIS DUEL-STATE THEORY 5011 03:44:57,360 --> 03:45:00,880 OF DOPAMINE FUNCTION AND IT 5012 03:45:00,880 --> 03:45:03,440 SUGGESTS THAT D2 RECEPTORS 5013 03:45:03,440 --> 03:45:06,200 FUNCTION CAN ALTER THE ENERGY 5014 03:45:06,200 --> 03:45:07,960 LANDSCAPE ON WHICH THE BRAIN IS 5015 03:45:07,960 --> 03:45:14,880 MOVING AND CHANGE THE SO WE 5016 03:45:14,880 --> 03:45:15,880 DIDN'T COLLECT SELF-REPORT 5017 03:45:15,880 --> 03:45:26,360 MEASURES IN THIS STUDY AND AND 5018 03:45:30,360 --> 03:45:33,360 NATURALLY THROUGH GENETICS OR 5019 03:45:33,360 --> 03:45:35,160 THROUGH PHARMACOLOGICAL 5020 03:45:35,160 --> 03:45:36,360 MANIPULATION CAN EXPLAIN THE 5021 03:45:36,360 --> 03:45:37,640 ENERGY DIFFERENCE SO IT'S THE 5022 03:45:37,640 --> 03:45:39,800 DIRECTION THAT THE STUDY WENT 5023 03:45:39,800 --> 03:45:43,040 AND SO WE DON'T KNOW IF IF THIS 5024 03:45:43,040 --> 03:45:47,160 IS MORE CORRELATED THAN 5025 03:45:47,160 --> 03:45:51,560 SELF-REPORT AND THEY ALLOW US TO 5026 03:45:51,560 --> 03:45:53,240 TO CONNECT BRAIN TO NEURO 5027 03:45:53,240 --> 03:45:54,080 TRANSMITTER FUNCTION WHICH I 5028 03:45:54,080 --> 03:46:04,360 THINK IS EXCITING. 5029 03:46:06,600 --> 03:46:10,000 >>I ALSO IT LOOKS LIKE ROBERT 5030 03:46:10,000 --> 03:46:16,280 WILSON HAD A QUESTION. 5031 03:46:16,280 --> 03:46:18,840 >>GREAT TALKS. 5032 03:46:18,840 --> 03:46:23,520 I GUESS THIS IS THE OLDER 5033 03:46:23,520 --> 03:46:26,000 SPEAKERS AND JUST THINKING ABOUT 5034 03:46:26,000 --> 03:46:30,080 THESE LARGER SCALE NETWORKS AND 5035 03:46:30,080 --> 03:46:32,080 MAYBE THE STABILITY TEE THAT 5036 03:46:32,080 --> 03:46:33,720 PROGRESS OR MILLER TALKED ABOUT 5037 03:46:33,720 --> 03:46:37,040 OF THESE NETWORKS AND WITH 5038 03:46:37,040 --> 03:46:41,040 RESPECT TO THE DRIFT AND IS 5039 03:46:41,040 --> 03:46:45,760 THERE A SCALE A PREFERRED TIME 5040 03:46:45,760 --> 03:46:46,680 SCALE THAT WE TAUGHT TO THINK 5041 03:46:46,680 --> 03:46:50,120 ABOUT IN TERMS OF THESE NETWORKS 5042 03:46:50,120 --> 03:46:52,800 AND OR IS IT A HIERARCHY OF 5043 03:46:52,800 --> 03:46:54,800 SCALES AND A DIFFERENT 5044 03:46:54,800 --> 03:46:58,160 COMMUTATIONS IN BEHAVIORS 5045 03:46:58,160 --> 03:47:00,680 REPRESENTED AT DIFFERENT TIME 5046 03:47:00,680 --> 03:47:05,320 SCALES AND LANCE SCALES AND I 5047 03:47:05,320 --> 03:47:15,840 GUESS WITH A IT'S OF TIME AND OF 5048 03:47:20,600 --> 03:47:20,800 SPACE. 5049 03:47:20,800 --> 03:47:24,000 >>I'M HAPPY TO START IF THAT'S 5050 03:47:24,000 --> 03:47:24,200 OKAY. 5051 03:47:24,200 --> 03:47:26,400 >>WE THINK OF I WOULD NOT 5052 03:47:26,400 --> 03:47:29,680 FOLLOW THE TRAP OF THINKING THAT 5053 03:47:29,680 --> 03:47:31,480 OSCILLATIONS BANDS LIKE ALPHA 5054 03:47:31,480 --> 03:47:33,040 AND THEY DO SPECIFIC FUNCTIONS 5055 03:47:33,040 --> 03:47:35,520 AND IT'S LIKE SAYING SPIKE OF A 5056 03:47:35,520 --> 03:47:36,240 SPECIFIC FUNCTION. 5057 03:47:36,240 --> 03:47:37,600 IT DEPENDS ON WHERE THEY'RE 5058 03:47:37,600 --> 03:47:38,560 SPIKEING AND WHAT THEY'RE 5059 03:47:38,560 --> 03:47:40,120 SPIKING TO AND WHAT NETWORKS ARE 5060 03:47:40,120 --> 03:47:42,360 IN AND THESE DIFFERENT FREQUENCY 5061 03:47:42,360 --> 03:47:44,240 BANDS, FIRST OF ALL, IT'S ONE 5062 03:47:44,240 --> 03:47:46,280 THING THE FREQUENCY BANDS WERE 5063 03:47:46,280 --> 03:47:48,320 MADE 150 YEARS AGO AND ARE VERY 5064 03:47:48,320 --> 03:47:51,200 ARBITRARY AND THEY DON'T 5065 03:47:51,200 --> 03:47:52,680 CORRESPOND TO REAL TRUE 5066 03:47:52,680 --> 03:47:55,480 DIFFERENCES BETWEEN THEM. 5067 03:47:55,480 --> 03:47:58,240 THINK OF THEM NOT AS A -- THINK 5068 03:47:58,240 --> 03:47:59,720 OF THEM AS DIFFERENT ENERGY 5069 03:47:59,720 --> 03:48:00,600 STATES IN THE NETWORK. 5070 03:48:00,600 --> 03:48:01,880 WHEN THERE'S A LOT OF SPIKING 5071 03:48:01,880 --> 03:48:04,360 GOING ON THERE'S A LOT OF GAMMA 5072 03:48:04,360 --> 03:48:06,040 AND HIGH LEVELS OF SPIKING AND 5073 03:48:06,040 --> 03:48:08,320 AT LOWER LEVELS, BETA, ALPHA, 5074 03:48:08,320 --> 03:48:10,680 THERE'S MORE LOW-LEVELS OF 5075 03:48:10,680 --> 03:48:12,480 SPIKING AND MORE SLOW FREQUENCY 5076 03:48:12,480 --> 03:48:14,360 AND WE THINK BECAUSE OF THOSE 5077 03:48:14,360 --> 03:48:15,920 DIFFERENCES, THE LOWER 5078 03:48:15,920 --> 03:48:17,200 FREQUENCIES ARE MORE APPROPRIATE 5079 03:48:17,200 --> 03:48:20,760 OR BETTER USED FOR A TOP-DOWN 5080 03:48:20,760 --> 03:48:23,960 CONTROL MECHANISM BECAUSE YOU 5081 03:48:23,960 --> 03:48:27,960 GET THE WAVES ACTING ON OF A 5082 03:48:27,960 --> 03:48:29,280 LARGER SPECIAL SCALE SO THEY'RE 5083 03:48:29,280 --> 03:48:30,920 BETTER TO ORGANIZE THE SCALE YOU 5084 03:48:30,920 --> 03:48:34,200 NEED FOR TOP DOWN CONTROL AND IF 5085 03:48:34,200 --> 03:48:38,680 YOU LOOK AT FACTOR BALL BY 5086 03:48:38,680 --> 03:48:39,280 LESLIE KAY WHEN LOTS OF GAMMA 5087 03:48:39,280 --> 03:48:45,280 AND THE SPIKE LINES WITH THE 5088 03:48:45,280 --> 03:48:51,080 SNIFFS AND AND IT SHIFTS INTO 5089 03:48:51,080 --> 03:48:52,000 DATA BANDS AND IT'S VERY LOCAL 5090 03:48:52,000 --> 03:48:54,560 AND IT'S VERY MUCH THE FEET 5091 03:48:54,560 --> 03:48:55,800 FORWARD STUFF COMING IN AND 5092 03:48:55,800 --> 03:48:58,200 SWITCHES THE BETA AND SOMETHING 5093 03:48:58,200 --> 03:48:59,320 THE WHOLE FACTORY SYSTEM COULD 5094 03:48:59,320 --> 03:49:02,840 BE PART OF THE MOTOR SYSTEM OF 5095 03:49:02,840 --> 03:49:04,040 CINCO NICED AND THINK OF THIS AS 5096 03:49:04,040 --> 03:49:05,720 NOT HAVING A FUNCTION BUT 5097 03:49:05,720 --> 03:49:07,120 SWITCHING TO DIFFERENT ENERGY 5098 03:49:07,120 --> 03:49:08,440 STATES AND COMPATIBLE WITH 5099 03:49:08,440 --> 03:49:13,800 DIFFERENT FUNCTIONS. 5100 03:49:13,800 --> 03:49:16,360 >>AND I WOULD LIKE TO ASK A 5101 03:49:16,360 --> 03:49:22,400 FOLLOW-UP QUESTION TO DANI ABOUT 5102 03:49:22,400 --> 03:49:24,320 THIS AND IF YOU LOOKED AT THE 5103 03:49:24,320 --> 03:49:24,920 RELATIONSHIP BETWEEN COST 5104 03:49:24,920 --> 03:49:32,000 MEASURES AND FREQUENCY BANDS AND 5105 03:49:32,000 --> 03:49:33,800 SWITCH INTERESTING AN ALPHA 5106 03:49:33,800 --> 03:49:37,000 DOMINATED TO A DAMN A GOM 5107 03:49:37,000 --> 03:49:40,960 INNATED DOES THAT TELL YOU ABOUT 5108 03:49:40,960 --> 03:49:45,160 THE COST SWITCHING BETWEEN THOSE 5109 03:49:45,160 --> 03:49:45,400 STATES. 5110 03:49:45,400 --> 03:49:46,960 >>THE MAJORITY OF OUR WORK IN 5111 03:49:46,960 --> 03:49:49,120 THE SPACE SO FAR HAS USED 5112 03:49:49,120 --> 03:49:51,480 FUNCTIONAL MAGNETIC HOWEVER WE 5113 03:49:51,480 --> 03:49:53,720 DO HAVE ONE STUDY WHERE THE 5114 03:49:53,720 --> 03:49:56,240 CITIES WE WERE EXAMINING WERE 5115 03:49:56,240 --> 03:49:58,560 POWER ACROSS DIFFERENT REGIONS 5116 03:49:58,560 --> 03:49:59,120 AND IN PARTICULAR FREQUENCY 5117 03:49:59,120 --> 03:50:00,560 BANDS AND SO THAT IS A PAPER 5118 03:50:00,560 --> 03:50:03,960 THAT WAS PUBLISHED IN THE 5119 03:50:03,960 --> 03:50:14,440 RECORDS AND I DID SEE ANA'S 5120 03:50:22,720 --> 03:50:23,600 HANDOUT AND I DON'T KNOW IF YOU 5121 03:50:23,600 --> 03:50:25,280 WANT TO SAY A LITTLE BIT ON THIS 5122 03:50:25,280 --> 03:50:25,440 TOO. 5123 03:50:25,440 --> 03:50:28,600 >>YEAH, I WAS GOING TO COMMENT 5124 03:50:28,600 --> 03:50:32,160 THAT THE NETWORK BUT SINCE WE 5125 03:50:32,160 --> 03:50:33,760 ARE TALKING ABOUT THE ENERGY 5126 03:50:33,760 --> 03:50:37,320 ISSUE AND I ACTUALLY ALSO HAD A 5127 03:50:37,320 --> 03:50:40,280 QUESTION FOR YOU AND WHICH IS 5128 03:50:40,280 --> 03:50:44,840 HOW DO YOU SEE THESE ENERGY 5129 03:50:44,840 --> 03:50:46,840 CONSUMPTION THROUGH AGING AND 5130 03:50:46,840 --> 03:50:49,680 BECAUSE IN YOUR EQUATION, I 5131 03:50:49,680 --> 03:50:52,800 MEAN, YOU HAVE THE DISTANCE AND 5132 03:50:52,800 --> 03:50:54,720 THE CHANGES AND THE STRUCTURAL 5133 03:50:54,720 --> 03:50:58,640 CHANGES MAY BE VERY, VERY SUBTLE 5134 03:50:58,640 --> 03:51:09,160 AND THROUGH THE YEARS AND YET 5135 03:51:13,640 --> 03:51:16,520 THROUGH THE PROCESS AND SO SO 5136 03:51:16,520 --> 03:51:23,960 WHAT DO YOU THINK WOULD BE 5137 03:51:23,960 --> 03:51:25,280 RELEVANT CONSIDERATION TO 5138 03:51:25,280 --> 03:51:28,880 CAPTURE THESE FUNCTIONAL CHANGES 5139 03:51:28,880 --> 03:51:32,320 TA GET MODIFIED OVER A LONG TIME 5140 03:51:32,320 --> 03:51:34,520 IN SUBTLE WAYS? 5141 03:51:34,520 --> 03:51:36,680 >>I THINK THAT'S A GREAT 5142 03:51:36,680 --> 03:51:37,160 QUESTION TOO. 5143 03:51:37,160 --> 03:51:38,680 THE CONTROL ENERGY ESTIMATES ARE 5144 03:51:38,680 --> 03:51:41,280 ONES THAT DEPEND ON CHANGES IN 5145 03:51:41,280 --> 03:51:44,880 STRUCTURE WHICH CAN BE SMALL OR 5146 03:51:44,880 --> 03:51:46,320 CHANGES IN ACTIVATION PATTERNS, 5147 03:51:46,320 --> 03:51:48,680 RIGHT AND IT'S THE COMBINATION 5148 03:51:48,680 --> 03:51:50,360 OF THOSE TWO RAILROADS' ABLE 5149 03:51:50,360 --> 03:51:52,600 THAT'S INFORMS THE CONTROL 5150 03:51:52,600 --> 03:51:57,440 ENERGY ESTIMATE AND SO AS AIMING 5151 03:51:57,440 --> 03:51:58,480 OCCURS BECAUSE THERE ARE CHANGES 5152 03:51:58,480 --> 03:52:00,960 BOTH IN ACTIVATION PROFILES AND 5153 03:52:00,960 --> 03:52:03,480 IN STRUCTURE THE CONTROL ENERGY 5154 03:52:03,480 --> 03:52:05,120 WOULD SENSE THAT HOWEVER, I 5155 03:52:05,120 --> 03:52:08,360 THINK IT'S ALSO INTERESTING TO 5156 03:52:08,360 --> 03:52:10,520 ASK WHICH OF THOSE IS DRIVING 5157 03:52:10,520 --> 03:52:11,800 THE ESTIMATE MORE SO ONE WAY 5158 03:52:11,800 --> 03:52:16,200 THAT CAN YOU DO THAT IS TO USE A 5159 03:52:16,200 --> 03:52:17,600 TEMPLATE STRUCTURAL CONNECTIVITY 5160 03:52:17,600 --> 03:52:19,800 FROM A SET OF YOUNG, HEALTHY 5161 03:52:19,800 --> 03:52:21,240 ADULTS AND YOU CAN SEE HOW MUCH 5162 03:52:21,240 --> 03:52:23,160 ENERGY WAS REQUIRED FOR THESE 5163 03:52:23,160 --> 03:52:25,200 TRANSITION OWNS THAT NETWORK AND 5164 03:52:25,200 --> 03:52:26,240 IT WOULD GIVE YOU AN ESTIMATE OF 5165 03:52:26,240 --> 03:52:28,280 HOW MUCH THE CHANGED IN 5166 03:52:28,280 --> 03:52:29,680 ACTIVATION IS DRIVING YOUR 5167 03:52:29,680 --> 03:52:32,320 RESULTS IN CONTRAST TO WHEN YOU 5168 03:52:32,320 --> 03:52:34,680 USE PARTICIPANTS STRUCTURAL 5169 03:52:34,680 --> 03:52:36,560 CONNECTIVITY THEN YOU ARE 5170 03:52:36,560 --> 03:52:38,560 ASSESSING MORE THE ROLE OF 5171 03:52:38,560 --> 03:52:40,880 DIFFERENCES IF THE THE PATTERN 5172 03:52:40,880 --> 03:52:42,240 OF CONNECTIVITY DRIVING AND THE 5173 03:52:42,240 --> 03:52:52,200 CONTROL ENERGY ESTIMATE SO JUST 5174 03:52:52,200 --> 03:52:54,680 TO BACK UP TO YOUR BROADER 5175 03:52:54,680 --> 03:52:56,920 QUESTION IS HOW DO WE THINK 5176 03:52:56,920 --> 03:52:59,160 ABOUT CHANGES IN CONTROL ENERGY 5177 03:52:59,160 --> 03:53:00,800 WITH AGE WE HAVEN'T LOOKED AT 5178 03:53:00,800 --> 03:53:02,840 OLDER AGE YET BUT WE HAVE LOOKED 5179 03:53:02,840 --> 03:53:05,280 AT DEVELOPMENT AND WE SEE FOR 5180 03:53:05,280 --> 03:53:07,600 EXAMPLE, THAT IN YOUTH, BETWEEN 5181 03:53:07,600 --> 03:53:09,040 THE AIMS OF EIGHT YEARS AND # 2 5182 03:53:09,040 --> 03:53:12,680 YEARS OF AGE WE SEE A MARKED 5183 03:53:12,680 --> 03:53:14,920 DECREASE IN THE CONTROL ENERGY 5184 03:53:14,920 --> 03:53:18,200 REQUIRED TO ACTIVATE FRONTAL FOR 5185 03:53:18,200 --> 03:53:19,800 ITSAL CORTEX CONSISTENT WITH 5186 03:53:19,800 --> 03:53:21,920 INDIVIDUAL DIFFERENCES IN 5187 03:53:21,920 --> 03:53:24,200 EXECUTIVE FUNCTION SO FOR THE 5188 03:53:24,200 --> 03:53:25,360 YOUTH WHO C HIGHER LEVELS OF 5189 03:53:25,360 --> 03:53:26,440 EXECUTIVE FUNCTION WE SEE THAT 5190 03:53:26,440 --> 03:53:29,520 THEY REQUIRE LESS CONTROL ENERGY 5191 03:53:29,520 --> 03:53:32,520 FOR FRONTAL CORTEX DUE TO THE 5192 03:53:32,520 --> 03:53:34,240 CONSTRUCT SURE CONNECTIVITY SO 5193 03:53:34,240 --> 03:53:36,440 THAT IS CENTERING ASK DUGS TO US 5194 03:53:36,440 --> 03:53:38,920 THIS IS AN APPROACH THAT CAN BE 5195 03:53:38,920 --> 03:53:43,840 USED ACROSS TIME SCALES AND IN 5196 03:53:43,840 --> 03:53:45,840 THE LIFESPAN BUT WE HAVE NOT YET 5197 03:53:45,840 --> 03:53:50,160 APPLIED TO LATER AGE. 5198 03:53:50,160 --> 03:53:51,520 S THAT HAVE IS VERY INTERESTING 5199 03:53:51,520 --> 03:53:53,160 IF EIGHT TO 22 BECAUSE FOR WHAT 5200 03:53:53,160 --> 03:53:55,800 YOU SAY, IF IT'S EFFECTIVE 5201 03:53:55,800 --> 03:53:57,680 CONTROL AND THAT MAY BE RELATED 5202 03:53:57,680 --> 03:54:01,880 TO THE LEVEL OF MY LYNNATION OF 5203 03:54:01,880 --> 03:54:07,040 THE TRACKS THAT ARE TAP NORTH 5204 03:54:07,040 --> 03:54:10,080 AND SO YOU WONDER IF THAT 5205 03:54:10,080 --> 03:54:11,160 INCREASING MYELIN ALSO WILL 5206 03:54:11,160 --> 03:54:14,920 PRODUCE AND INCREASE IN 5207 03:54:14,920 --> 03:54:16,520 SYNCHRONY OF THE SIGNALS BECAUSE 5208 03:54:16,520 --> 03:54:23,360 NOW THIS TRACTS ARE FULLY 5209 03:54:23,360 --> 03:54:33,520 DEVELOPED. 5210 03:54:39,640 --> 03:54:41,640 >>IS COLDATED WITH THE 5211 03:54:41,640 --> 03:54:45,280 INDIVIDUALS EX THAT COULD BE 5212 03:54:45,280 --> 03:54:48,080 REALLY INTERESTING AND IT WOULD 5213 03:54:48,080 --> 03:54:49,480 ADDRESS THE QUESTION OF WHETHER 5214 03:54:49,480 --> 03:54:52,640 THE DEGREE OF MY LYNNATION IS IN 5215 03:54:52,640 --> 03:54:54,320 PART A FACTOR CONNECTED TO THOSE 5216 03:54:54,320 --> 03:54:59,320 THAT I'VE BEEN DESCRIBING. 5217 03:54:59,320 --> 03:55:06,200 >>I THINK A NAN HAD A RELATED 5218 03:55:06,200 --> 03:55:07,160 QUESTION THAT WOULD BE USEFUL 5219 03:55:07,160 --> 03:55:07,600 FOR THE GROUP. 5220 03:55:07,600 --> 03:55:08,920 >>THANK YOU, THIS IS EXACTLY 5221 03:55:08,920 --> 03:55:10,360 WHAT MY QUESTION IS GETTING AT. 5222 03:55:10,360 --> 03:55:11,960 WE'VE BEEN SPENDING TIME HERE 5223 03:55:11,960 --> 03:55:13,280 TALKING ABOUT CHALLENGES THAT 5224 03:55:13,280 --> 03:55:15,560 MAY BE UNIQUE TO MODELING THE 5225 03:55:15,560 --> 03:55:18,360 BRAIN AND USING COMPUTATIONAL 5226 03:55:18,360 --> 03:55:19,480 APPROACHES AND YOU KNOW, MY 5227 03:55:19,480 --> 03:55:23,400 QUESTION IS, REALLY, WHETHER 5228 03:55:23,400 --> 03:55:25,120 THERE ARE UNIQUE LIMITATIONS 5229 03:55:25,120 --> 03:55:26,520 THAT MIGHT EXIST IN THE CONTEXT 5230 03:55:26,520 --> 03:55:28,400 OF LOOKING AT THE AGING BRAIN 5231 03:55:28,400 --> 03:55:30,080 AND YOU JUST TOUCHED ON THAT 5232 03:55:30,080 --> 03:55:34,600 TALKING ABOUT HOW WITH AGING AND 5233 03:55:34,600 --> 03:55:37,640 IT COULD BE HARD TO DETECT AND 5234 03:55:37,640 --> 03:55:40,720 WHAT ELSE WOULD YOU MIND TALKING 5235 03:55:40,720 --> 03:55:44,160 MORE ABOUT PARTICULAR CHALLENGES 5236 03:55:44,160 --> 03:55:45,440 BUT ALSO LIMITATIONS AND COMING 5237 03:55:45,440 --> 03:55:47,480 UP TO APPLY THESE APPROACHES IN 5238 03:55:47,480 --> 03:55:57,840 AGING IN THE BRAIN? 5239 03:55:58,120 --> 03:56:01,480 >>OTHER PEOPLE HAVE DIFFERENT 5240 03:56:01,480 --> 03:56:04,760 ANSWERS BUT WE APPLY AGE 5241 03:56:04,760 --> 03:56:14,600 PREDICTION MODELS TO DATA LIKE 5242 03:56:14,600 --> 03:56:16,680 FDG PET AND YOU CAN USE A DEEP 5243 03:56:16,680 --> 03:56:19,840 NURRAL NETWORK AND WHAT HAVE YOU 5244 03:56:19,840 --> 03:56:21,440 TO PREDICT SOMEONE'S AGE AND 5245 03:56:21,440 --> 03:56:23,680 COMPARE IT TO THE CHRONOLOGICAL 5246 03:56:23,680 --> 03:56:25,400 AGE AND EXPLORE WHAT THE MODEL 5247 03:56:25,400 --> 03:56:29,160 IS USING TO MAKE THAT PREDICTION 5248 03:56:29,160 --> 03:56:30,120 AND THAT CAN TELL YOU SOMETHING 5249 03:56:30,120 --> 03:56:32,720 ABOUT THE BIOLOGICAL MECHANISMS, 5250 03:56:32,720 --> 03:56:34,320 THE SCALE AND THE PHYSIOLOGY OF 5251 03:56:34,320 --> 03:56:35,840 THE DATA THAT YOU ARE USING TO 5252 03:56:35,840 --> 03:56:38,760 ASK THAT QUESTION. 5253 03:56:38,760 --> 03:56:41,920 AND SO, WHEN WE DO THAT WITH FDG 5254 03:56:41,920 --> 03:56:46,640 PET, YOU KNOW, WHAT WE SEE IS IT 5255 03:56:46,640 --> 03:56:47,920 TRANSITION WHERE YOUNGER FOLKS, 5256 03:56:47,920 --> 03:56:50,520 THE PREDICTIONS MORE DEPEND 5257 03:56:50,520 --> 03:56:52,600 APARTMENT ON THE FRONTAL LOBE 5258 03:56:52,600 --> 03:56:53,800 AND OLDER PREDICTIONS IT DEPENDS 5259 03:56:53,800 --> 03:56:56,280 ON THE BACK AND THERE'S THIS 5260 03:56:56,280 --> 03:56:58,800 GRADIENT FROM FRONT TO BACK AND 5261 03:56:58,800 --> 03:57:01,560 IT IS THE SAME THING YOU SEE IN 5262 03:57:01,560 --> 03:57:04,400 FUNCTIONAL MRI ACTIVATION 5263 03:57:04,400 --> 03:57:06,840 STUDIES SO WHEN WE HEAR THE SAME 5264 03:57:06,840 --> 03:57:09,760 THING, TO STRUCTURAL MRI, YOU 5265 03:57:09,760 --> 03:57:13,240 CAN ALSO PREDICT SOMEONE'S AGE 5266 03:57:13,240 --> 03:57:15,240 AND THERE'S TOTALLY DIFFERENT 5267 03:57:15,240 --> 03:57:16,680 FEATURES IN THAT DATA THAT ARE 5268 03:57:16,680 --> 03:57:19,200 BEING USED TO MAKE THAT PREDICT 5269 03:57:19,200 --> 03:57:22,560 AND IT'S SSF DYNAMICS SO THE 5270 03:57:22,560 --> 03:57:27,560 PROBLEM WHEN THE CHALLENGE IS 5271 03:57:27,560 --> 03:57:28,960 WHEN YOU HAVE THESE BIOLOGICAL 5272 03:57:28,960 --> 03:57:33,200 AGE ESTIMATES FROM BRAIN DATA AT 5273 03:57:33,200 --> 03:57:36,320 THE SCALE, WHAT EXACTLY DOES 5274 03:57:36,320 --> 03:57:38,160 THAT GAP TELL YOU BETWEEN 5275 03:57:38,160 --> 03:57:39,480 BIOLOGICAL ASK PREDICTIVE AGE. 5276 03:57:39,480 --> 03:57:40,760 SOME THINGS ARE THE SAME AND 5277 03:57:40,760 --> 03:57:41,960 SOME THINGS ARE DIFFERENT AND 5278 03:57:41,960 --> 03:57:44,560 STRUCTURAL MRI IT'S CSF DYNAMICS 5279 03:57:44,560 --> 03:57:45,880 THAT ARE DRIVING THE PREDICTION 5280 03:57:45,880 --> 03:57:50,400 AND THEN FDG PET, IT'S BRAIN 5281 03:57:50,400 --> 03:57:55,720 ENERGY CHANGES WITH AGE THAT ARE 5282 03:57:55,720 --> 03:57:56,280 DRIVING PRIEST DICTION AND 5283 03:57:56,280 --> 03:57:57,080 HAVING FRAMEWORK TO UNDERSTAND 5284 03:57:57,080 --> 03:57:58,440 THE DIFFERENT THINGS FROM 5285 03:57:58,440 --> 03:58:02,280 MULTIPLE PERSPECTIVES IS A 5286 03:58:02,280 --> 03:58:12,480 CHALLENGE. 5287 03:58:15,120 --> 03:58:17,560 >>I HAVE A QUESTION FOR Mr. 5288 03:58:17,560 --> 03:58:18,000 JONES. 5289 03:58:18,000 --> 03:58:22,200 I'M WONDERING, SO WHEN YOU TALK 5290 03:58:22,200 --> 03:58:25,800 DIVIDED PATIENTS INTO LANGUAGE 5291 03:58:25,800 --> 03:58:28,840 ORP MEMORY OR SENSORY, YOU HAVE 5292 03:58:28,840 --> 03:58:30,600 FIRST CLASSES OF PATIENTS AND 5293 03:58:30,600 --> 03:58:32,000 I'M WONDERING IF THERE'S DEMAND 5294 03:58:32,000 --> 03:58:37,920 FROM THE CLINICAL SIDE FOR SIZE 5295 03:58:37,920 --> 03:58:48,440 AND ON THE BEHAVIORS SIDE AND 5296 03:59:04,640 --> 03:59:06,560 YOU DESIGN DIGITAL TESTS FOR 5297 03:59:06,560 --> 03:59:07,640 THOSE SPECIFIC THINGS AND 5298 03:59:07,640 --> 03:59:10,600 EVERYONE GETS THEM, THAT'S WHAT 5299 03:59:10,600 --> 03:59:11,320 WE NEED. 5300 03:59:11,320 --> 03:59:13,680 WE DON'T HAVE THAT AND UP WITH 5301 03:59:13,680 --> 03:59:19,600 OF THE CHALLENGES THAT WE 5302 03:59:19,600 --> 03:59:23,680 ACTUALLY LIKE THEIR EXECUTIVE 5303 03:59:23,680 --> 03:59:34,200 COGNITIVABILITY THEY CANNOT AND 5304 03:59:34,200 --> 03:59:38,240 IT'S ONE DOMAIN AND IT SHOWS ON 5305 03:59:38,240 --> 03:59:47,480 ANY SORT OF TEST YOU DO AND THE 5306 03:59:47,480 --> 03:59:50,720 TASK PERFORMING AND WE DON'T 5307 03:59:50,720 --> 03:59:54,760 HAVE GOOD ASSESSMENTS FOR THEM 5308 03:59:54,760 --> 03:59:59,720 AT ALL AND AND IT'S A BIG 5309 03:59:59,720 --> 04:00:09,880 CHALLENGE. 5310 04:00:10,640 --> 04:00:13,040 >>I WILL ECHO TO BE AWARE OF 5311 04:00:13,040 --> 04:00:16,320 THE NIH TOOLBOX WHICH IS MULTI 5312 04:00:16,320 --> 04:00:17,640 DIMENSIONAL BRIEF MEASURES 5313 04:00:17,640 --> 04:00:18,920 ASSESSING COGNITIVE EMOTIONAL 5314 04:00:18,920 --> 04:00:23,040 AND MOTOR SENSORY FROM AGES 3-85 5315 04:00:23,040 --> 04:00:24,840 WHICH WOULD MEET THE NEED FOR A 5316 04:00:24,840 --> 04:00:26,080 STANDARD SET OF MEASURES USED AS 5317 04:00:26,080 --> 04:00:28,120 A COMMON CURRENCY ACROSS DIVERSE 5318 04:00:28,120 --> 04:00:32,480 STUDY DESIGNS AND SETTINGS. 5319 04:00:32,480 --> 04:00:35,040 AND THERE'S A LINK IN THE CHAT 5320 04:00:35,040 --> 04:00:37,040 FOR FOLKS ON THE ZOOM CALL AND 5321 04:00:37,040 --> 04:00:38,720 WE'LL MAKE SURE TO ACCEPTED IT 5322 04:00:38,720 --> 04:00:40,400 OUT AND POST MATERIALS FOR FOLKS 5323 04:00:40,400 --> 04:00:44,800 WATCHING AT HOME. 5324 04:00:44,800 --> 04:00:54,480 >>YEAH, I WOULD LIKE COME BACK 5325 04:00:54,480 --> 04:00:56,280 TO AMANDA'S QUESTION AND IT'S A 5326 04:00:56,280 --> 04:00:58,560 QUESTION THAT COMES OVER AND 5327 04:00:58,560 --> 04:01:01,240 OVER ON MODELING. 5328 04:01:01,240 --> 04:01:03,840 MAYBE I HAVE A VERY SIMPLISTIC 5329 04:01:03,840 --> 04:01:06,120 NOTION OF IT BUT FROM A 5330 04:01:06,120 --> 04:01:07,760 PERSPECTIVE THE REAL WORLD IS 5331 04:01:07,760 --> 04:01:11,920 VERY MESSY AND PART OF THE ROLE 5332 04:01:11,920 --> 04:01:17,320 OF MODELING IS TO GET TO THE 5333 04:01:17,320 --> 04:01:20,600 BEAR BONES THAT ARE RELEVANT TO 5334 04:01:20,600 --> 04:01:22,720 A SPECIFIC SITUATION. 5335 04:01:22,720 --> 04:01:33,160 SO, IN THAT SENSE, IN THIS 5336 04:01:34,920 --> 04:01:38,360 USEFULNESS I THINK I COMPLETELY 5337 04:01:38,360 --> 04:01:39,960 AGREE WITH FAVORITE ONE OF THE 5338 04:01:39,960 --> 04:01:42,240 NET TRICKS THAT TESTFULNESS OF 5339 04:01:42,240 --> 04:01:44,320 THE MODEL THAT THE PREDICTIVE 5340 04:01:44,320 --> 04:01:47,600 VALUE OF THAT MODEL SO THAT IS 5341 04:01:47,600 --> 04:01:48,680 ONE WAY TO GO. 5342 04:01:48,680 --> 04:01:51,320 ON THE OTHER HAND I THINK THAT 5343 04:01:51,320 --> 04:01:54,880 ALSO THIS MODELS THEY CAN BE 5344 04:01:54,880 --> 04:01:59,880 GENERATING HYPOTHESIS OF THE 5345 04:01:59,880 --> 04:02:02,720 MECHANISMS AND IN THIS SENSE, 5346 04:02:02,720 --> 04:02:06,920 THE LINK TO THE BASIC RESEARCH 5347 04:02:06,920 --> 04:02:08,360 AND IT'S FUNDAMENTAL. 5348 04:02:08,360 --> 04:02:11,040 WHY, BECAUSE THE MODEL CAN'T BE 5349 04:02:11,040 --> 04:02:13,160 THEY GO THE GENERATION OR 5350 04:02:13,160 --> 04:02:14,680 HYPOTHESIS CAN MAKE TESTABLE TO 5351 04:02:14,680 --> 04:02:19,400 WHAT EXTENT THAT IT'S PROPER AND 5352 04:02:19,400 --> 04:02:23,520 ON THE OTHER, ALSO, BASIC 5353 04:02:23,520 --> 04:02:27,400 RESEARCH CAN FEEDBACK TO THE 5354 04:02:27,400 --> 04:02:30,080 MODELING AND THAT'S JUST LINKING 5355 04:02:30,080 --> 04:02:33,960 WITH THE FIRST SECTION OF THESE 5356 04:02:33,960 --> 04:02:36,520 WORKS THAT IS WHERE THIS 5357 04:02:36,520 --> 04:02:44,720 INTERACTION CAN BE INTEGRATED 5358 04:02:44,720 --> 04:02:49,400 DATA FROM THE MOLECULAR TO THE 5359 04:02:49,400 --> 04:02:59,840 WHOLE BRAIN. 5360 04:02:59,840 --> 04:03:01,080 >>I WILL ADD I AGREE. 5361 04:03:01,080 --> 04:03:02,720 A LOT OF WORK WE'RE DOING, A LOT 5362 04:03:02,720 --> 04:03:04,320 OF THE HYPOTHESIS WE'RE TESTING 5363 04:03:04,320 --> 04:03:08,120 ON THESE DYNAMICS THEY CAME FROM 5364 04:03:08,120 --> 04:03:09,920 COMPUTATIONAL MODEL -- YOU KNOW, 5365 04:03:09,920 --> 04:03:11,520 IT'S TOO HARD TO FIGURE OUT 5366 04:03:11,520 --> 04:03:13,120 COGNITION FOR FIRST PRINCIPLES, 5367 04:03:13,120 --> 04:03:16,080 YOU NEED MODELS TO TELL YOU WHAT 5368 04:03:16,080 --> 04:03:17,360 PROPERTIES AND YOU WOULD NEVER 5369 04:03:17,360 --> 04:03:19,520 THINK TO LOOK FORWARD TO BEGIN 5370 04:03:19,520 --> 04:03:21,320 WITH AND TO PROCESS OF REFINING 5371 04:03:21,320 --> 04:03:26,000 THE MODELS AND MAKING NEW 5372 04:03:26,000 --> 04:03:27,320 REPREDICTIONS AND IT'S ALL 5373 04:03:27,320 --> 04:03:27,960 BEAUTIFUL. 5374 04:03:27,960 --> 04:03:33,040 >>I GREATLY AGREE. 5375 04:03:33,040 --> 04:03:35,400 BRAIN DATA PEOPLE TAKE IT DOWN 5376 04:03:35,400 --> 04:03:36,720 TO PARTICLE PHYSICS. 5377 04:03:36,720 --> 04:03:42,520 WELL, WE'VE GOT OTHER QUESTIONS 5378 04:03:42,520 --> 04:03:47,000 TO ANSWER SO I TRY TO TAKE A 5379 04:03:47,000 --> 04:03:48,440 PRAGMATIC APPROACH AND THIS IS 5380 04:03:48,440 --> 04:03:53,640 THIS IS A MODEL YOU CAN USE TO 5381 04:03:53,640 --> 04:04:04,160 ASK QUESTIONS BUT OUR DATA AT 5382 04:04:09,600 --> 04:04:10,880 LEAST WITH PETS THERE'S A VERY 5383 04:04:10,880 --> 04:04:15,280 TIGHT CORRELATION BETWEEN THESE 5384 04:04:15,280 --> 04:04:17,280 PATTERNS THE COGNITIVE SYNDROMES 5385 04:04:17,280 --> 04:04:20,200 THAT PATIENTS HAVE SO THERE'S A 5386 04:04:20,200 --> 04:04:23,360 LINK ASK IT'S VERY IMPORTANT AND 5387 04:04:23,360 --> 04:04:24,880 HAVING MODELS EXPLAIN THAT LINK 5388 04:04:24,880 --> 04:04:28,000 ARE GOOD FOR ASKING QUESTIONS IT 5389 04:04:28,000 --> 04:04:32,080 DOESN'T MEAN THEY'RE CAPITAL T 5390 04:04:32,080 --> 04:04:36,720 TRUE. 5391 04:04:36,720 --> 04:04:38,720 >>THERE WAS A QUESTION FROM THE 5392 04:04:38,720 --> 04:04:41,240 VIDEO CAST SPECIFICALLY FOR 5393 04:04:41,240 --> 04:04:43,680 Dr. MILLER IN TERMS IF YOU 5394 04:04:43,680 --> 04:04:44,840 COULD RECLASSIFY OF FREQUENCY 5395 04:04:44,840 --> 04:04:46,480 BANDS THAT THEY HAVE MEANINGFUL 5396 04:04:46,480 --> 04:04:47,200 PHYSIOLOGICAL FUNCTIONS WOULD 5397 04:04:47,200 --> 04:04:50,520 YOU DO SO AND IF SO HOW? 5398 04:04:50,520 --> 04:04:54,360 >>WELL, I WOULD STICK TO 5399 04:04:54,360 --> 04:04:54,680 GENERAL TEE. 5400 04:04:54,680 --> 04:04:56,560 I WOULDN'T DIVIDE FREQUENCIES 5401 04:04:56,560 --> 04:04:58,720 THE INTO ALPHA VERSUS BETA. 5402 04:04:58,720 --> 04:05:00,960 THERE'S GOING TO BE A LOT OF 5403 04:05:00,960 --> 04:05:02,000 INDIVIDUALITY AND IT'S SHIPPED 5404 04:05:02,000 --> 04:05:06,080 AROUND FROM BRAIN TO BRAIN AND 5405 04:05:06,080 --> 04:05:08,800 THE LOW FREQUENCY VERSUS HIGH 5406 04:05:08,800 --> 04:05:12,760 FREQUENCY IS A BIG DINK TANKION 5407 04:05:12,760 --> 04:05:15,000 AND THE HIGHER FREQUENCIES ARE 5408 04:05:15,000 --> 04:05:16,440 SENSORY INFORMATION AND CREATING 5409 04:05:16,440 --> 04:05:19,560 MOTOR OUTPUT AND LOW FREQUENCIES 5410 04:05:19,560 --> 04:05:20,880 THAT CAN PUSH AROUND THAT WILL 5411 04:05:20,880 --> 04:05:28,320 PLAY MORE OF A ROLE IN 5412 04:05:28,320 --> 04:05:31,520 CONTROLLING GAMMA IS MAIN LOCAL 5413 04:05:31,520 --> 04:05:33,640 PHENOMENON BUT IT'S INFORMATION 5414 04:05:33,640 --> 04:05:35,320 AND THERE'S THOUGHT IT CROSSES 5415 04:05:35,320 --> 04:05:43,520 TO NETTA BARZ THETA HELPS IT TRG 5416 04:05:43,520 --> 04:05:45,600 DIS DANCES WE USE GAMMA AND 5417 04:05:45,600 --> 04:05:50,480 NETTA BARZILANETTHETA BUT IT'S S 5418 04:05:50,480 --> 04:05:51,640 BETWEEN FREQUENCIES THAT WE 5419 04:05:51,640 --> 04:06:02,080 SHOULD BE MORE FOCUSED ON. 5420 04:06:02,560 --> 04:06:07,800 O. 5421 04:06:07,800 --> 04:06:13,040 >>I HAVE A QUESTION FOR DAVE 5422 04:06:13,040 --> 04:06:14,720 AND MAYBE EARL YOU CAN WEIGH ON 5423 04:06:14,720 --> 04:06:15,680 THIS AS WELL. 5424 04:06:15,680 --> 04:06:16,960 DAVE, YOU SHOW COOL DATA ABOUT 5425 04:06:16,960 --> 04:06:21,280 MAKING PREDICTIONS USING FDG PAD 5426 04:06:21,280 --> 04:06:21,640 FOR COGNITION. 5427 04:06:21,640 --> 04:06:25,120 DO YOU THINK IT'S AS EASY TO 5428 04:06:25,120 --> 04:06:27,080 PREDICT POTENTIALLY ANYTHING 5429 04:06:27,080 --> 04:06:28,960 RELATE TODAY MOW BILL AND 5430 04:06:28,960 --> 04:06:32,840 MOBILITY TO DECLINE USING THOSE 5431 04:06:32,840 --> 04:06:33,800 SAME TOOLS? 5432 04:06:33,800 --> 04:06:35,240 >>SO, I THINK SO. 5433 04:06:35,240 --> 04:06:39,480 WE'RE WORKING ON THAT NOW AND 5434 04:06:39,480 --> 04:06:40,560 THIS IS, I WOULD LIKE TO MAKE 5435 04:06:40,560 --> 04:06:42,120 THINGS CONCRETE SO I JUST THINK 5436 04:06:42,120 --> 04:06:43,440 ABOUT MY PATIENTS BECAUSE THEY 5437 04:06:43,440 --> 04:06:53,880 ASK THIS QUESTION AND FOR 5438 04:06:57,800 --> 04:06:58,560 ALZHEIMER'S, SOMETIMES THOSE 5439 04:06:58,560 --> 04:06:59,880 PATIENTS ARE IN NURSING HOMES 5440 04:06:59,880 --> 04:07:01,080 WITHIN TWO YEARS AND I SEE IT 5441 04:07:01,080 --> 04:07:03,680 AND I KNOW THAT. 5442 04:07:03,680 --> 04:07:05,320 I SEE OTHER PATIENTS WHERE IT'S 5443 04:07:05,320 --> 04:07:06,880 10 YEARS OR LONGER SO I'LL START 5444 04:07:06,880 --> 04:07:09,560 OFF BY TELLING MY PATIENTS, THIS 5445 04:07:09,560 --> 04:07:11,200 IS A WIDE RANGE OF VARIABILITY 5446 04:07:11,200 --> 04:07:15,120 I'VE SEEN IN MY CLINIC AND THEY 5447 04:07:15,120 --> 04:07:16,600 WANT TO KNOW ABOUT THEM AND WE 5448 04:07:16,600 --> 04:07:19,440 HAVE A PAPER IF YOU CAN SUB 5449 04:07:19,440 --> 04:07:22,000 PHENOTYPE THIS AN ATOMICALLY AND 5450 04:07:22,000 --> 04:07:24,640 VERSUS A RIGHT FRONTAL OR LEFT 5451 04:07:24,640 --> 04:07:27,160 FRONTAL OR HETERO MOTTAL THOSE 5452 04:07:27,160 --> 04:07:29,160 HAVE DIFFERENT CLINICAL 5453 04:07:29,160 --> 04:07:32,680 TRAJECTORIES THAT CAPTURES THE 5454 04:07:32,680 --> 04:07:38,080 RATES WE BELIEVE AND THE YOUNG 5455 04:07:38,080 --> 04:07:39,240 ALZHEIMER'S PATIENTS ARE THINK 5456 04:07:39,240 --> 04:07:41,800 THAT'S GOING TO BE VERY 5457 04:07:41,800 --> 04:07:46,240 PREDICTIVE OF A RELATIVELY LESS 5458 04:07:46,240 --> 04:07:47,200 A BLESS I HAVE COURSE. 5459 04:07:47,200 --> 04:07:49,160 AND SO, HOW WILL WE DO THAT? 5460 04:07:49,160 --> 04:07:51,360 I WOULD TAKE ALL THE PATIENTS OF 5461 04:07:51,360 --> 04:07:53,520 THE FDG PET PATTERN AND MATCH IT 5462 04:07:53,520 --> 04:07:54,960 TO EVERYONE IN OUR DATABASE WHO 5463 04:07:54,960 --> 04:07:58,240 HAS THAT PATTERN AND WE HAVE 5464 04:07:58,240 --> 04:07:59,320 LONGITUDINAL DATA ON THEM AND I 5465 04:07:59,320 --> 04:08:01,440 COULD SAY WELL, EVERYONE ELSE 5466 04:08:01,440 --> 04:08:04,040 WHO HAS HAD BRAIN PATTERN LIKE 5467 04:08:04,040 --> 04:08:05,560 THIS IS THE CLINICAL OUTCOME AND 5468 04:08:05,560 --> 04:08:07,880 I THINK THAT'S GOING TO WORK AND 5469 04:08:07,880 --> 04:08:14,640 WE HAVEN'T DONE THAT YET. 5470 04:08:14,640 --> 04:08:15,960 ALSO, ONE OTHER IMPORTANT THINGS 5471 04:08:15,960 --> 04:08:17,360 IT'S ONLY IF THEY'RE A SYNDROME 5472 04:08:17,360 --> 04:08:19,360 AND THE DISABILITY IS CAPTURED 5473 04:08:19,360 --> 04:08:21,440 BY THE DIS TEASE FAN METING IN 5474 04:08:21,440 --> 04:08:23,960 THEIR FDG PEST AND IF THEY HAVE 5475 04:08:23,960 --> 04:08:27,240 A DISORDER MISSED. 5476 04:08:27,240 --> 04:08:33,560 THEY WILL GET DISABILITY FROM 5477 04:08:33,560 --> 04:08:37,680 NORMAL INAND IT'S JUST AN 5478 04:08:37,680 --> 04:08:39,000 EXAMPLE AND WE HAVE TO TAKE INTO 5479 04:08:39,000 --> 04:08:40,400 ACCOUNT THE PATIENTS ECONOMICS 5480 04:08:40,400 --> 04:08:47,920 TEX'' COP TEXTAND MULTIPLE FACTE 5481 04:08:47,920 --> 04:08:52,560 PREDICT THINGS LIKE THIS. 5482 04:08:52,560 --> 04:08:54,320 >>EARL, ANY THOUGHTS ON THAT 5483 04:08:54,320 --> 04:08:54,680 QUESTION? 5484 04:08:54,680 --> 04:08:56,720 >>I MEAN, LOOK, WE ARE A VERY 5485 04:08:56,720 --> 04:08:58,040 BASIC NEUROSCIENCE LAB. 5486 04:08:58,040 --> 04:08:59,600 WE DON'T STUDY PATIENT GROUPS 5487 04:08:59,600 --> 04:09:04,040 BUT WE HAVE A MODEL OF SENSORY 5488 04:09:04,040 --> 04:09:05,600 OVERLOAD OF AUTISM WHERE WE 5489 04:09:05,600 --> 04:09:08,160 THINK IT'S IMBALANCE BETWEEN THE 5490 04:09:08,160 --> 04:09:09,480 LOW AND HIGH FREQUENCY. 5491 04:09:09,480 --> 04:09:11,600 WHEN THEY'RE LOW AND HIGH AND 5492 04:09:11,600 --> 04:09:13,760 THE TOPPED DOWN CONTROL BASED ON 5493 04:09:13,760 --> 04:09:15,920 LOW FREQUENCIES CAN'T FILTER OUT 5494 04:09:15,920 --> 04:09:17,720 THE INWANTED SENSORY SIGNALS AND 5495 04:09:17,720 --> 04:09:19,760 YOU GET SENSORY OVERLOAD AND 5496 04:09:19,760 --> 04:09:21,400 IT'S CONSISTENT WITH THE 5497 04:09:21,400 --> 04:09:24,160 OBSERVATIONS OF EEG AND ASD 5498 04:09:24,160 --> 04:09:24,920 POPULATIONS. 5499 04:09:24,920 --> 04:09:25,800 WE'RE TRYING TO START A HAVE 5500 04:09:25,800 --> 04:09:26,760 HE'S OF INVESTIGATIONS WHERE 5501 04:09:26,760 --> 04:09:28,880 WE'RE GOING TO ACTUALLY 5502 04:09:28,880 --> 04:09:30,760 MANIPULATE THE RHYTHMS USING 5503 04:09:30,760 --> 04:09:33,040 STIMULATIONS AND IF WE CAN TURN 5504 04:09:33,040 --> 04:09:34,960 DOWN THE LOWER FREQUENCY CONTROL 5505 04:09:34,960 --> 04:09:36,760 RHYTHM WE SHOULD LET THE FOOD 5506 04:09:36,760 --> 04:09:38,200 GATES OF SENSORY INFORMATION 5507 04:09:38,200 --> 04:09:41,840 COME IN AND CREATE A MODEL OF 5508 04:09:41,840 --> 04:09:43,280 SENSORY OVERLOAD AND THEN FIX IT 5509 04:09:43,280 --> 04:09:45,880 BY TURNING UP THE RHYTHM AND SO 5510 04:09:45,880 --> 04:09:47,280 THAT PROPER FILTERING COMES 5511 04:09:47,280 --> 04:09:49,040 BACK. 5512 04:09:49,040 --> 04:09:50,960 SO, PATIENT POPULATIONS BUT 5513 04:09:50,960 --> 04:09:52,520 WE'RE HOPING TO ACTUALLY CREATE 5514 04:09:52,520 --> 04:09:55,320 A DISEASE LIKE MODEL USING BUY 5515 04:09:55,320 --> 04:09:59,920 VIRTUE OF MANIPULATING THE BRAIN 5516 04:09:59,920 --> 04:10:02,360 ROOMS. 5517 04:10:02,360 --> 04:10:04,120 >>I THINK THAT'S WHAT YOU JUST 5518 04:10:04,120 --> 04:10:06,240 SAID EARLIER IS GREAT AND I 5519 04:10:06,240 --> 04:10:07,760 THINK THAT IS REALLY TIES 5520 04:10:07,760 --> 04:10:12,920 TOGETHER I THINK OF DANI'S WORK 5521 04:10:12,920 --> 04:10:16,800 AND BRAIN ENERGETICS. 5522 04:10:16,800 --> 04:10:18,600 LET'S SAY WE KNOW THE BRAIN 5523 04:10:18,600 --> 04:10:20,000 CONFIGURATIONS OF OUR PATIENTS 5524 04:10:20,000 --> 04:10:28,760 IT WILL HELP DIAGNOSE AND 5525 04:10:28,760 --> 04:10:29,640 PROGNOSIS. 5526 04:10:29,640 --> 04:10:31,000 MAYBE IT WILL BE EASIER TO MAKE 5527 04:10:31,000 --> 04:10:33,960 THESE STATE TRANSITIONS, IT WILL 5528 04:10:33,960 --> 04:10:35,000 BE LESSENNER JET TICK AND 5529 04:10:35,000 --> 04:10:36,680 THEY'LL BE ABLE TO DO IT WHICH 5530 04:10:36,680 --> 04:10:39,520 MEANS THEY'LL GET IT TO PERFORM 5531 04:10:39,520 --> 04:10:41,520 EXECUTIVE FUNCTIONS AGAIN BEFORE 5532 04:10:41,520 --> 04:10:42,120 THEY WEREN'T. 5533 04:10:42,120 --> 04:10:44,960 SO EVEN IF YOU DON'T BELIEVE 5534 04:10:44,960 --> 04:10:48,640 THIS LEVEL IS CAUSAL, IT'S A 5535 04:10:48,640 --> 04:10:50,080 PARADIGM YOU CAN USE TO TREAT 5536 04:10:50,080 --> 04:10:51,240 PATIENTS EVEN IF YOU DON'T THINK 5537 04:10:51,240 --> 04:10:52,080 IT'S CAUSAL. 5538 04:10:52,080 --> 04:10:55,760 >>I BELIEVE IT IS CAUSAL. 5539 04:10:55,760 --> 04:10:58,520 IT'S HARD TO IMAGINE IT'S NOT. 5540 04:10:58,520 --> 04:10:59,720 IT'S A LARGE ORGANIZATION OF 5541 04:10:59,720 --> 04:11:01,040 BRAIN ACTIVITY. 5542 04:11:01,040 --> 04:11:03,960 TO THAT POINT, WE'RE DOING THESE 5543 04:11:03,960 --> 04:11:07,360 EXPERIMENTS USING NEW TECHNOLOGY 5544 04:11:07,360 --> 04:11:08,160 ULTRAFAST CLOSE LOOP STIMULATION 5545 04:11:08,160 --> 04:11:09,480 AND ELECTRICAL STIMULATION WHERE 5546 04:11:09,480 --> 04:11:11,880 EVERYBODY NOW AND ANIMALS IS 5547 04:11:11,880 --> 04:11:15,760 DOING GENETICS AND WHY ARE WE 5548 04:11:15,760 --> 04:11:17,920 DOING ELECTRICITY INSTEAD 5549 04:11:17,920 --> 04:11:19,080 BECAUSE WHEN WE FIGURE OUT HOW 5550 04:11:19,080 --> 04:11:20,640 THOSE SYSTEMS WORKS INSIDE THE 5551 04:11:20,640 --> 04:11:23,120 BRAIN WE CAN THEN REPLAY THE 5552 04:11:23,120 --> 04:11:26,920 RHYTHMS USING NON-INVASIVE 5553 04:11:26,920 --> 04:11:28,000 STIMULATION AND WORK ALONG 5554 04:11:28,000 --> 04:11:30,480 TREATMENT PLANS AND HAVE PEOPLE 5555 04:11:30,480 --> 04:11:31,920 REINFORCE THE RIGHT BRAIN RHYTHM 5556 04:11:31,920 --> 04:11:33,720 WHEN PEOPLE ARE IN TRAINING 5557 04:11:33,720 --> 04:11:37,880 SESSIONS THAT WILL REINFORCE THE 5558 04:11:37,880 --> 04:11:40,040 STRUCTURE OF THE BRAIN THAT DANI 5559 04:11:40,040 --> 04:11:40,760 TALKED ABOUT. 5560 04:11:40,760 --> 04:11:42,760 YOU WILL NEVER DO THAT BY 5561 04:11:42,760 --> 04:11:45,240 INJECTING A VIRUS INTO A HUMAN 5562 04:11:45,240 --> 04:11:45,840 BRAIN. 5563 04:11:45,840 --> 04:11:47,160 IT'S ALWAYS A RESEARCH TOOL. 5564 04:11:47,160 --> 04:11:48,640 USING ELECTRICAL STIMULATION IS 5565 04:11:48,640 --> 04:11:53,680 A PATH TOWARDS ACTUAL TREATMENT. 5566 04:11:53,680 --> 04:11:54,440 >>David Jones: THE ONLY WAY TO 5567 04:11:54,440 --> 04:11:56,120 GET US THERE IS WE NEED THEORIES 5568 04:11:56,120 --> 04:11:58,880 AND MODELS THATS OPERATE AT THIS 5569 04:11:58,880 --> 04:11:59,240 LEVEL. 5570 04:11:59,240 --> 04:12:00,640 THAT WILL GUIDE THE TREATMENTS 5571 04:12:00,640 --> 04:12:03,960 AND MEASURING A RESPONSES AND I 5572 04:12:03,960 --> 04:12:05,720 THINK THAT'S WHERE A LOT OF WORK 5573 04:12:05,720 --> 04:12:07,160 NEEDS TO BE DONE. 5574 04:12:07,160 --> 04:12:17,520 >>I CON AGREE MORE. 5575 04:12:17,920 --> 04:12:25,880 >>IF I CAN, I JUST HAVE -- IT'S 5576 04:12:25,880 --> 04:12:27,680 SELF-SERVING BUT WE HAVE A 5577 04:12:27,680 --> 04:12:28,800 PLATFORM AND IT'S BUILT TO BE 5578 04:12:28,800 --> 04:12:34,280 USED NOT ONLY IN HUMANS BUT ALSO 5579 04:12:34,280 --> 04:12:39,000 IN MACAQUE AND IN MICE AND RATS. 5580 04:12:39,000 --> 04:12:43,160 COMING BACK TO THE ISSUE OF -- 5581 04:12:43,160 --> 04:12:47,760 IT'S POSSIBLE TO SIMULATE THE 5582 04:12:47,760 --> 04:12:51,560 TMS OR TTC STIMULATION IN THE 5583 04:12:51,560 --> 04:12:56,240 MODEL AND MODEL THE POTENTIAL 5584 04:12:56,240 --> 04:12:59,600 DYNAMICS THAT IT PRODUCES ORIGIN 5585 04:12:59,600 --> 04:13:03,160 IF THERE'S A PARADIGM THAT 5586 04:13:03,160 --> 04:13:04,360 SUGGESTS A TREATMENT, ALSO IT 5587 04:13:04,360 --> 04:13:12,080 CAN BE TESTED AT THE MODEL LEVEL 5588 04:13:12,080 --> 04:13:19,360 WITH MEASURING PROPER CHANGES IL 5589 04:13:19,360 --> 04:13:22,960 OF THE ELECTRIC FIELDS OR I MEAN 5590 04:13:22,960 --> 04:13:33,400 WE CAN MODEL AT ANY LEVEL. 5591 04:13:34,400 --> 04:13:35,840 "CAN FACILITATE THE TESTING OF 5592 04:13:35,840 --> 04:13:42,600 THE THERAPISTS. 5593 04:13:42,600 --> 04:13:44,240 >>I AGREE. 5594 04:13:44,240 --> 04:13:46,320 >>I GUESS JUST TO FOLLOW-UP ON 5595 04:13:46,320 --> 04:13:47,760 THAT AT THAT POINT ABOUT 5596 04:13:47,760 --> 04:13:48,840 SIMULATED DATA AND THE ROLE OF 5597 04:13:48,840 --> 04:13:50,520 SORT OF SIMULATED DATA WITH 5598 04:13:50,520 --> 04:13:52,640 REGARDS TO MODELING, YOU KNOW, 5599 04:13:52,640 --> 04:13:55,040 YOU TALKED ABOUT THAT AND PAOLA 5600 04:13:55,040 --> 04:13:56,720 TALKED ABOUT IT IN THE FIRST 5601 04:13:56,720 --> 04:13:59,800 SESSION AND I'M CURIOUS IF YOU 5602 04:13:59,800 --> 04:14:00,880 COULD OR OTHERS FEEL LIKE WHAT 5603 04:14:00,880 --> 04:14:02,800 IS THE STATE OF SORT OF 5604 04:14:02,800 --> 04:14:04,640 SIMULATED DATASETS IN SORT OF 5605 04:14:04,640 --> 04:14:06,000 SURVEYING THESE SORT OF 5606 04:14:06,000 --> 04:14:07,200 COMPUTATIONAL MODELING 5607 04:14:07,200 --> 04:14:07,480 APPROACHES? 5608 04:14:07,480 --> 04:14:10,120 ARE THE SIMULATIONS GOOD ENOUGH 5609 04:14:10,120 --> 04:14:12,480 OR DO WE NEED BETTER SIMULATION 5610 04:14:12,480 --> 04:14:22,320 AND DO WE NEED TO JUST. 5611 04:14:22,320 --> 04:14:24,760 >>WELL, THINK THAT ONE SIZE 5612 04:14:24,760 --> 04:14:26,160 DOESN'T FIT ALL BUT I WILL GIVE 5613 04:14:26,160 --> 04:14:31,320 YOU AN EXAMPLE OF WHEN 5614 04:14:31,320 --> 04:14:34,480 COLLABORATOR AND FRIEND VICTOR 5615 04:14:34,480 --> 04:14:41,960 GERSA WHO WAS INTERESTED IN 5616 04:14:41,960 --> 04:14:45,840 SIMULATING SEIZURES IN 5617 04:14:45,840 --> 04:14:47,240 EPILEPSIES CASES AND RIGHT NOW 5618 04:14:47,240 --> 04:14:52,280 THE SIMULATION -- HE IS LIVES IN 5619 04:14:52,280 --> 04:14:56,480 FRANCE AND SO THEY ARE RUNNING A 5620 04:14:56,480 --> 04:14:58,120 CLINICAL TRIAL WITH THE 5621 04:14:58,120 --> 04:15:01,880 SIMULATIONS EMBEDDED INTO THE 5622 04:15:01,880 --> 04:15:04,160 DETERMINATION OF THE SITE OF THE 5623 04:15:04,160 --> 04:15:07,000 ORIGIN OF THE SEIZURE BEFORE THE 5624 04:15:07,000 --> 04:15:09,920 NEURO SURGEONS COME ABOUT AND 5625 04:15:09,920 --> 04:15:15,360 DISSECT THE AREA. 5626 04:15:15,360 --> 04:15:19,200 BECAUSE THIS MODEL CAN BE SO 5627 04:15:19,200 --> 04:15:25,160 SENSITIVE THAT CAN BY PASS THE 5628 04:15:25,160 --> 04:15:27,560 EFFICACY OF FINDING THIS 5629 04:15:27,560 --> 04:15:31,440 LOCATION OF THIS SEIZURES BASED 5630 04:15:31,440 --> 04:15:35,760 ON CURRENT METHODS ON EEG AND 5631 04:15:35,760 --> 04:15:36,360 ALL THESE. 5632 04:15:36,360 --> 04:15:38,120 SO IT'S A CLINICAL TRIAL THAT IS 5633 04:15:38,120 --> 04:15:40,360 GOING ON RIGHT NOW. 5634 04:15:40,360 --> 04:15:43,200 SO, IT CAN BE, AGAIN, YOU KNOW, 5635 04:15:43,200 --> 04:15:45,600 THE MOLDS ARE NOT PERFECT AND 5636 04:15:45,600 --> 04:15:51,080 CAN BE EXTREMELY USEFUL. 5637 04:15:51,080 --> 04:15:52,880 AND THAT'S WHERE THE PREDICTIVE 5638 04:15:52,880 --> 04:15:58,560 VALUE I THINK COMES ABOUT THAT 5639 04:15:58,560 --> 04:16:00,240 IS RELEVANT. 5640 04:16:00,240 --> 04:16:02,520 IT'S MUCH MORE SPECIFIC RIGHT 5641 04:16:02,520 --> 04:16:05,480 NOW WE HAVE FOR THE LOCAL 5642 04:16:05,480 --> 04:16:08,320 DYNAMICS WE HAVE A LIBRARY OF 5643 04:16:08,320 --> 04:16:11,080 MAYBE 257 DIFFERENT MODELS AND 5644 04:16:11,080 --> 04:16:18,760 THEY GO FROM THE DYNAMICS AND 5645 04:16:18,760 --> 04:16:20,800 DEPENDING ON THE HYPOTHESIS THAT 5646 04:16:20,800 --> 04:16:26,280 ONE HAS, YOU KNOW, YOU CAN HAVE 5647 04:16:26,280 --> 04:16:27,760 CURRENTS IF THAT'S WHAT THE 5648 04:16:27,760 --> 04:16:30,920 INTEREST IS AND SO I THINK THE 5649 04:16:30,920 --> 04:16:33,560 QUESTION AGAIN IS, WHAT IS A 5650 04:16:33,560 --> 04:16:43,800 USEFUL MODEL. 5651 04:16:44,760 --> 04:16:46,560 >>I LOVE TO SHARE DATA WITH 5652 04:16:46,560 --> 04:16:48,400 MODELERS AND I HAVE A LARGE 5653 04:16:48,400 --> 04:16:50,400 CATEGORY OF DATA FROM ANIMALS 5654 04:16:50,400 --> 04:16:51,760 PERFORMING COGNITIVE AND 5655 04:16:51,760 --> 04:16:53,240 ELECTRODES ALL OVER THE BRAIN 5656 04:16:53,240 --> 04:16:57,080 AND LFPs AND SPIKES. 5657 04:16:57,080 --> 04:16:58,080 ANYONE INTERESTED WORKING 5658 04:16:58,080 --> 04:17:01,600 TOGETHER WITH THIS DATA, CONTACT 5659 04:17:01,600 --> 04:17:01,760 ME. 5660 04:17:01,760 --> 04:17:02,680 I MEAN THAT. 5661 04:17:02,680 --> 04:17:03,320 >>YES. 5662 04:17:03,320 --> 04:17:05,640 I MEAN IT TOO. 5663 04:17:05,640 --> 04:17:06,240 THIS IS AWESOME. 5664 04:17:06,240 --> 04:17:09,520 >>COOL. 5665 04:17:09,520 --> 04:17:13,120 >>I'D LIKE IT MAKE A COMMENT. 5666 04:17:13,120 --> 04:17:16,560 AS I HEARD MY NAME. 5667 04:17:16,560 --> 04:17:18,000 I DIDN'T HAVE TIME TO DISCUSS 5668 04:17:18,000 --> 04:17:21,000 THIS EARLIER AND I OF WORKED 5669 04:17:21,000 --> 04:17:26,640 WITH FOR A COUPLE OF YEARS WITH 5670 04:17:26,640 --> 04:17:28,920 COMPANY AND DEVELOPED SO 5671 04:17:28,920 --> 04:17:32,520 PHYSICAL INDICATES PROCEDURES 5672 04:17:32,520 --> 04:17:43,080 SIMULATION AND OF THE STATISTICS 5673 04:17:47,360 --> 04:17:50,920 AND LANGUAGE MEASURE PROCESSING 5674 04:17:50,920 --> 04:17:57,960 AND IT'S CALLED EACH AND AND USE 5675 04:17:57,960 --> 04:17:59,240 HAPPENING PROCESSING TOOLS TO 5676 04:17:59,240 --> 04:18:03,560 SIMULATE DATA FROM YOUR ORIGINAL 5677 04:18:03,560 --> 04:18:05,680 DATASET. 5678 04:18:05,680 --> 04:18:07,920 I WAS VERY SKEPTICAL AND THEY 5679 04:18:07,920 --> 04:18:09,880 HAD A REAL DATASET AND THEY GAVE 5680 04:18:09,880 --> 04:18:13,400 ME A SIMULATED DATASET THAT IS 5681 04:18:13,400 --> 04:18:15,080 STATISTICAL REPRESENTATION OF 5682 04:18:15,080 --> 04:18:17,560 THE ORIGINAL DATA AND THEY CAN'T 5683 04:18:17,560 --> 04:18:18,880 SIMULATE IF I GIVE THEM A 5684 04:18:18,880 --> 04:18:22,200 THOUSAND OBSERVATION, I CAN'T 5685 04:18:22,200 --> 04:18:23,160 SIMULATE A HUNDRED THOUSAND AND 5686 04:18:23,160 --> 04:18:25,240 HOW CAN THAT BE? 5687 04:18:25,240 --> 04:18:28,120 IT TURNS OUT, SO I STARTED VERY 5688 04:18:28,120 --> 04:18:29,560 SKEPTICAL AND I BELIEVE THAT WAS 5689 04:18:29,560 --> 04:18:31,520 POSSIBLE AND I HAVE TO SAY I'M 5690 04:18:31,520 --> 04:18:34,240 VERY IMPRESSED BY WHAT THEY GAVE 5691 04:18:34,240 --> 04:18:36,720 ME BACK. 5692 04:18:36,720 --> 04:18:44,920 SO REALLY DATASET AND THE GOAL 5693 04:18:44,920 --> 04:18:46,840 WAS TO CREATE WOULD BE SHARED 5694 04:18:46,840 --> 04:18:48,520 WITHOUT ANY RESTRICTIONS IT 5695 04:18:48,520 --> 04:18:49,720 TURNS OUT THAT NOW MY STUDENTS 5696 04:18:49,720 --> 04:18:52,760 ARE USING THEM FOR TUNING UP 5697 04:18:52,760 --> 04:18:54,680 THEIR MODELS BECAUSE THOSE ARE 5698 04:18:54,680 --> 04:19:00,080 AN INCREDIBLE RESOURCE THAT IS 5699 04:19:00,080 --> 04:19:01,800 ESSENTIALLY DATA WILL NOT HAVE A 5700 04:19:01,800 --> 04:19:03,320 PRELIMINARY AND YOU CAN DO IT AS 5701 04:19:03,320 --> 04:19:06,160 MUCH AS WANT AND FOR REALLY 5702 04:19:06,160 --> 04:19:10,360 VALIDATION OF MODELS AND THEY 5703 04:19:10,360 --> 04:19:20,840 SEEM TO BE TO FACILITATE TO 5704 04:19:26,360 --> 04:19:36,840 SHARED DATA AND WE SEE A LOT OF 5705 04:19:44,680 --> 04:19:45,480 MODELS THAT DEVELOP AND THIS 5706 04:19:45,480 --> 04:19:47,920 COULD BE A REALLY USEFUL 5707 04:19:47,920 --> 04:19:48,760 BENCHMARK DATA THAT CAN BE 5708 04:19:48,760 --> 04:19:50,560 SHARED WITH NO RESTRICTIONS AND 5709 04:19:50,560 --> 04:19:52,760 SO IT COULD BE AN INTERESTING 5710 04:19:52,760 --> 04:19:58,760 IDEA TO EXPLORE FURTHER. 5711 04:19:58,760 --> 04:20:03,920 >>I WAS VERY SKEPTICAL AND I'M 5712 04:20:03,920 --> 04:20:14,360 REALLY IMPRESSED BUT THAT. 5713 04:20:16,920 --> 04:20:19,880 >>EVEN IF THE SIMULATIONS ARE 5714 04:20:19,880 --> 04:20:24,600 GOOD FOR RESEARCH, I THINK OF AT 5715 04:20:24,600 --> 04:20:27,240 LEAST THERE'S A MATHEMATICAL 5716 04:20:27,240 --> 04:20:29,280 FORMULATION BEHIND ME THAT MAKES 5717 04:20:29,280 --> 04:20:31,280 THE SIMULATION VERY CONSISTENT 5718 04:20:31,280 --> 04:20:38,640 AND SO THAT DOESN'T MAKE IT TRUE 5719 04:20:38,640 --> 04:20:42,840 EX MAKES MAKES USEABLE THE 5720 04:20:42,840 --> 04:20:46,720 FACILITY USE THE DATA. 5721 04:20:46,720 --> 04:20:46,920 NOW -- 5722 04:20:46,920 --> 04:20:49,560 >>WHAT I FIND SURPRISING OF 5723 04:20:49,560 --> 04:20:51,080 THIS APPROACH IS THAT IT DOES 5724 04:20:51,080 --> 04:20:54,960 NOT RELY ON MATHEMATICAL MODELS. 5725 04:20:54,960 --> 04:20:57,560 YOU KNOW, YOU CAN PROVE YOURSELF 5726 04:20:57,560 --> 04:20:59,720 THAT ARE RIGHT IF YOU SIMULATE 5727 04:20:59,720 --> 04:21:01,280 DATA CONSISTENT WITH YOUR 5728 04:21:01,280 --> 04:21:02,120 HYPOTHESIS AND THAT HAPPENS A 5729 04:21:02,120 --> 04:21:02,480 LOT. 5730 04:21:02,480 --> 04:21:06,040 THESE ARE REALLY BASED ON SAY 5731 04:21:06,040 --> 04:21:09,240 IT'S A EMPIRICAL WAY OF DATA 5732 04:21:09,240 --> 04:21:11,600 FROM A LARGE DATASET, DL DATA 5733 04:21:11,600 --> 04:21:15,280 AND THERE'S NO MATHEMATICAL 5734 04:21:15,280 --> 04:21:16,400 FORMULATION BEHIND IT. 5735 04:21:16,400 --> 04:21:20,120 WHICH AGAIN, I SEE SURPRISING 5736 04:21:20,120 --> 04:21:22,400 AND SKEPTICAL PHASES WHICH I 5737 04:21:22,400 --> 04:21:24,680 AGREE AND I WAS VERY SKEPTICAL 5738 04:21:24,680 --> 04:21:27,080 AND IT CAN BE DONE BUT THIS IS 5739 04:21:27,080 --> 04:21:34,560 SOMETHING TO EXPLORE AND JUST 5740 04:21:34,560 --> 04:21:36,200 DISTRACTING INFORMATION ON EX AM 5741 04:21:36,200 --> 04:21:43,200 POLLS FROM THE REAL DATA. 5742 04:21:43,200 --> 04:21:45,320 >>SO ONE OTHER THING WE PLAN TO 5743 04:21:45,320 --> 04:21:47,920 DO, I'M INVOLVED WITH THE DATA 5744 04:21:47,920 --> 04:21:51,000 COMMUNITY THAT IS PART OF THE 5745 04:21:51,000 --> 04:21:53,480 PORTAL THAT WE STORE AND SHARE 5746 04:21:53,480 --> 04:21:56,000 AND MAINTAIN DATA FROM STUDIES 5747 04:21:56,000 --> 04:21:57,640 AND ONE OF THE THINGS WE PLAN TO 5748 04:21:57,640 --> 04:21:59,200 DO IS ACTUALLY CREATE A 5749 04:21:59,200 --> 04:22:01,560 CHALLENGE IN A COUPLE OF YEARS 5750 04:22:01,560 --> 04:22:08,000 WITH SYNTHETIC DATA AND SO LET'S 5751 04:22:08,000 --> 04:22:10,120 SAFE WE CAN -- I THINK IT'S 5752 04:22:10,120 --> 04:22:13,800 GOING TO BE USEFUL FOR TUNING UP 5753 04:22:13,800 --> 04:22:15,760 MODELS AND HELPING WITH THE 5754 04:22:15,760 --> 04:22:26,200 COMPUTATIONAL STRATEGIES. 5755 04:22:26,640 --> 04:22:28,960 >>I HAD A QUESTION FOR YOU, 5756 04:22:28,960 --> 04:22:31,600 DANI, ABOUT THE DIMENSIONALITY 5757 04:22:31,600 --> 04:22:32,760 OF THE STATE SPACE THAT YOU ARE 5758 04:22:32,760 --> 04:22:33,680 CONTROLLING OVER. 5759 04:22:33,680 --> 04:22:36,080 IS THAT A LOW D SPACE AND HOW 5760 04:22:36,080 --> 04:22:38,520 LOW D? 5761 04:22:38,520 --> 04:22:43,840 >>YEAH, WE'RE USING N AS THE 5762 04:22:43,840 --> 04:22:45,320 DIMENSIONS SO N BEING THE NUMBER 5763 04:22:45,320 --> 04:22:47,200 OF BRAIN REGIONS WE'RE STUDYING 5764 04:22:47,200 --> 04:22:48,760 AND THAT'S A COUPLE HUNDRED 5765 04:22:48,760 --> 04:22:49,480 TYPICALLY. 5766 04:22:49,480 --> 04:22:51,600 IT'S NOT VERY LOW D. 5767 04:22:51,600 --> 04:22:53,240 >>DO YOU THINK YOU NEED ALL 5768 04:22:53,240 --> 04:22:54,440 THAT OR DO YOU THINK COULD YOU 5769 04:22:54,440 --> 04:22:57,520 HAVE A LOWER DIMENSIONAL 5770 04:22:57,520 --> 04:23:00,800 REPRESENTATION IN THE SAME 5771 04:23:00,800 --> 04:23:01,040 FRAMEWORK? 5772 04:23:01,040 --> 04:23:02,880 >>I THINK THAT YOU COULD USE A 5773 04:23:02,880 --> 04:23:04,080 LOWER DIMENSIONAL 5774 04:23:04,080 --> 04:23:04,480 REPRESENTATION. 5775 04:23:04,480 --> 04:23:06,880 WE HAVE ONE STUDY THAT WAS DONE 5776 04:23:06,880 --> 04:23:11,520 IN COLLABORATION WITH ANN 5777 04:23:11,520 --> 04:23:16,120 GRABIAL AND USE USING CELLULAR 5778 04:23:16,120 --> 04:23:19,160 IMAGING IN MACAQUE MONKEYS TO 5779 04:23:19,160 --> 04:23:20,480 UNDERSTAND WHETHER ENERGY IS 5780 04:23:20,480 --> 04:23:22,400 ALTERED AS THE MOP KEYS ARE 5781 04:23:22,400 --> 04:23:24,200 DEVELOPING HABITS AND MOTOR 5782 04:23:24,200 --> 04:23:24,640 HABITS. 5783 04:23:24,640 --> 04:23:26,880 AND IN THAT CASE, THE 5784 04:23:26,880 --> 04:23:29,080 DIMENSIONALITY IS LOWER. 5785 04:23:29,080 --> 04:23:31,320 SO I DON'T THINK THAT THERE'S 5786 04:23:31,320 --> 04:23:32,520 NOTHING ABOUT THE APPROACH THAT 5787 04:23:32,520 --> 04:23:34,520 REQUIRES US TO HAVE AS MANY 5788 04:23:34,520 --> 04:23:35,720 DIMENSIONS AS WE HAVE AND I 5789 04:23:35,720 --> 04:23:36,680 THINK AN INTERESTING QUESTION IS 5790 04:23:36,680 --> 04:23:41,240 WHAT IS THE DIMENSIONALITY 5791 04:23:41,240 --> 04:23:42,280 NEEDED TO UNDERSTAND GROUP 5792 04:23:42,280 --> 04:23:43,480 DIFFERENCES IF WE'RE TALKING 5793 04:23:43,480 --> 04:23:45,720 ABOUT CLINICAL CONDITIONS AND 5794 04:23:45,720 --> 04:23:47,720 VERSUS TO UNDERSTAND INDIVIDUAL 5795 04:23:47,720 --> 04:23:49,120 DIFFERENCES IN COGNITIVABILITY, 5796 04:23:49,120 --> 04:23:51,960 FOR EXAMPLE, AND WE DO NEED A 5797 04:23:51,960 --> 04:23:56,560 HIGHER SPACE AND I THINK IT'S AN 5798 04:23:56,560 --> 04:24:00,800 OPEN QUESTION AND IT DETOYS MORE 5799 04:24:00,800 --> 04:24:01,080 ATTENTION. 5800 04:24:01,080 --> 04:24:03,280 >>IT'S SOMETHING THAT WE 5801 04:24:03,280 --> 04:24:07,040 STRUGGLED AND IT SEEMS LIKE 107 5802 04:24:07,040 --> 04:24:08,840 AND IT'S VERY GOOD FOR 5803 04:24:08,840 --> 04:24:10,120 REPRESENTING THE CONCEPT OF 5804 04:24:10,120 --> 04:24:14,520 ALZHEIMER'S IN GENERAL AND WHEN 5805 04:24:14,520 --> 04:24:16,680 YOU GET TO INDIVIDUALS IN MAKING 5806 04:24:16,680 --> 04:24:19,240 MORE PRECISE PREDICTIONS, 5807 04:24:19,240 --> 04:24:20,320 ESPECIALLY TRACKING ONE 5808 04:24:20,320 --> 04:24:21,320 INDIVIDUAL OVER TIME AND IT 5809 04:24:21,320 --> 04:24:23,480 SEEMS MORE THAN THE ORDER OF 50 5810 04:24:23,480 --> 04:24:25,760 OR 60 BUT AFTER THAT WE DON'T 5811 04:24:25,760 --> 04:24:30,560 SEEM TO GET VERY MUCH MORE 5812 04:24:30,560 --> 04:24:31,120 INFORMATION. 5813 04:24:31,120 --> 04:24:33,360 AND WE COMPARE THAT TO USING THE 5814 04:24:33,360 --> 04:24:36,480 WHOLE BRAIN SCAN, USING ALL THE 5815 04:24:36,480 --> 04:24:40,640 EYES AND BREAKING UP AND IT 5816 04:24:40,640 --> 04:24:44,320 SEEMS MORE LIKE 60 LARGE-SCALE 5817 04:24:44,320 --> 04:24:45,760 BRAIN CAPTURES THAT BETTER. 5818 04:24:45,760 --> 04:24:47,320 YOU GET MORE NOISE IF YOU USE 5819 04:24:47,320 --> 04:24:50,800 THE WHOLE IMAGE AND SO WE WERE 5820 04:24:50,800 --> 04:24:55,360 SURPRISED THAT 60 IS STILL LOW I 5821 04:24:55,360 --> 04:24:58,560 THINK. 5822 04:24:58,560 --> 04:25:02,520 >>SURPRISEING AND SUPER 5823 04:25:02,520 --> 04:25:12,720 INTERESTING. 5824 04:25:15,760 --> 04:25:18,320 >>THE BRAIN SIMILARITY GRAPHS 5825 04:25:18,320 --> 04:25:20,520 OR SIMILARLY PATIENT WISE TO ONE 5826 04:25:20,520 --> 04:25:21,000 ANOTHER. 5827 04:25:21,000 --> 04:25:24,800 IT'S A PATIENT THE EDGE IS THE 5828 04:25:24,800 --> 04:25:26,480 COSINE SIMILARITY BETWEEN THESE 5829 04:25:26,480 --> 04:25:28,320 LOW DIMENSIONAL REPRESENTATION 5830 04:25:28,320 --> 04:25:32,040 SO IN THOSE GRAPHS, IT'S 50 TO 5831 04:25:32,040 --> 04:25:32,440 60. 5832 04:25:32,440 --> 04:25:36,280 RIGHT NOW IT'S 50 AND IF WE GO 5833 04:25:36,280 --> 04:25:37,960 60, 70, 80, THEY'RE NOT HELPING 5834 04:25:37,960 --> 04:25:39,400 MAKING THOSE PREDICTIONS THAT 5835 04:25:39,400 --> 04:25:47,240 YOU SAW AND ALSO TRACKING AND 5836 04:25:47,240 --> 04:25:50,880 IDENTIFYING AND ONLY NEED 650 OR 5837 04:25:50,880 --> 04:25:59,440 0650 OR60 AND NOT HELPED BY GETG 5838 04:25:59,440 --> 04:26:01,520 ANYMORE. 5839 04:26:01,520 --> 04:26:03,280 >>WE HAVE A COUPLE MINUTES LEFT 5840 04:26:03,280 --> 04:26:08,000 HERE AND ANY OTHER PARTICIPANTS 5841 04:26:08,000 --> 04:26:10,400 AND ANY QUESTIONS OTHERWISE I 5842 04:26:10,400 --> 04:26:12,080 WILL ASK EACH SPEAKER TO SORT OF 5843 04:26:12,080 --> 04:26:14,080 GIVE THEIR SORT OF ONE BIGGEST 5844 04:26:14,080 --> 04:26:19,240 SORT OF TAKEAWAY GAP OR 5845 04:26:19,240 --> 04:26:24,880 OPPORTUNITY HERE. 5846 04:26:24,880 --> 04:26:26,680 >>ANY PARTICULAR ORDER, 5847 04:26:26,680 --> 04:26:26,960 SPEAKERS. 5848 04:26:26,960 --> 04:26:28,360 >>WE CAN GO IN SPEAKING ORDER. 5849 04:26:28,360 --> 04:26:30,080 YOU SPOKE UP FIRST. 5850 04:26:30,080 --> 04:26:30,360 YOU START. 5851 04:26:30,360 --> 04:26:32,920 >>I WOULD SAY THE 21s 5852 04:26:32,920 --> 04:26:33,400 21st SEPTEMBER REIS THE 5853 04:26:33,400 --> 04:26:36,840 SEPTEMBER REOF UNDERSTANDING THE 5854 04:26:36,840 --> 04:26:37,480 BRAINS IMMERSION PROPERTIES AND 5855 04:26:37,480 --> 04:26:39,120 THEY WERE IGNORED FOR A LONG 5856 04:26:39,120 --> 04:26:40,320 TIME AND NOW WE UNDERSTAND 5857 04:26:40,320 --> 04:26:41,520 ENOUGH ABOUT THE PIECES AND WE 5858 04:26:41,520 --> 04:26:45,560 HAVE TO START LOOKING AT THAT 5859 04:26:45,560 --> 04:26:47,480 LEVEL. 5860 04:26:47,480 --> 04:26:49,960 >>ANA. 5861 04:26:49,960 --> 04:26:53,000 >>YES THE TIME IS RIGHT FOR A 5862 04:26:53,000 --> 04:26:56,600 CHANGE IN PARADIGM TAPPING 5863 04:26:56,600 --> 04:27:00,000 MECHANISMS AND NOT ONLY AGING 5864 04:27:00,000 --> 04:27:05,320 BUT ALSO BRAIN DYSFUNCTION AND I 5865 04:27:05,320 --> 04:27:08,080 THINK THAT THE APPROACH HAS TO 5866 04:27:08,080 --> 04:27:11,760 HAVE A PERMANENT FEATURE. 5867 04:27:11,760 --> 04:27:15,160 THINDIVIDUALATION OF THE MEASURS 5868 04:27:15,160 --> 04:27:19,040 AND IT'S A WAY OF PUSHING 5869 04:27:19,040 --> 04:27:22,280 TOWARDS PRECISION MEDICINE. 5870 04:27:22,280 --> 04:27:25,440 >>I THINK WE NEED ONTOLOGY FOR 5871 04:27:25,440 --> 04:27:26,200 THE LARGE-SCALE ORGANIZATION OF 5872 04:27:26,200 --> 04:27:27,840 THE BRAIN THAT WE ALL UNDERSTAND 5873 04:27:27,840 --> 04:27:30,000 AND AGREE ON AND RELATE TO 5874 04:27:30,000 --> 04:27:33,080 CERTAIN CLINICAL SYNDROMES AND 5875 04:27:33,080 --> 04:27:39,560 SYMPTOMS AND A MODEL OF THAT TO 5876 04:27:39,560 --> 04:27:44,040 MEASURE THAT AND INTERVENE ON 5877 04:27:44,040 --> 04:27:47,440 THAT. 5878 04:27:47,440 --> 04:27:49,200 >>I THINK THAT ONE OF THE 5879 04:27:49,200 --> 04:27:50,360 CHALLENGE THAT'S IS GOING TO BE 5880 04:27:50,360 --> 04:27:51,920 PRODUCTIVE IN EVALUATING OVER 5881 04:27:51,920 --> 04:27:54,280 THE NEXT COUPLE OF YEARS IS 5882 04:27:54,280 --> 04:27:55,120 UNDERSTANDINGENNER JET TICKS IN 5883 04:27:55,120 --> 04:27:56,320 THE BRAIN FROM DIFFERENT 5884 04:27:56,320 --> 04:28:01,080 PERSPECTIVES AND MAYBE TRYING TO 5885 04:28:01,080 --> 04:28:02,240 OF CONNECTION THEM TOGETHER AND 5886 04:28:02,240 --> 04:28:04,560 MEASUREMENTS AND MODELS AND I 5887 04:28:04,560 --> 04:28:06,680 THINK THAT THAT IS PROVIDING US 5888 04:28:06,680 --> 04:28:08,080 WITH THIS BEAUTIFUL CONSTRAINTS 5889 04:28:08,080 --> 04:28:12,320 ON THE SYSTEM CAN PUSH US 5890 04:28:12,320 --> 04:28:16,640 FORWARD. 5891 04:28:16,640 --> 04:28:18,320 WELL, I THANK EVERYONE IN THIS 5892 04:28:18,320 --> 04:28:21,240 SESSION FOR NOT A GREAT SET OF 5893 04:28:21,240 --> 04:28:26,880 TALKS AND DISCUSSION AND I WILL 5894 04:28:26,880 --> 04:28:28,520 PASS TO LENNY FOR CLOSING 5895 04:28:28,520 --> 04:28:28,760 REMARKS. 5896 04:28:28,760 --> 04:28:31,040 >>YES, I WOULD LIKE TO THANK 5897 04:28:31,040 --> 04:28:33,040 ALL TODAY'S PRESENTERS AND 5898 04:28:33,040 --> 04:28:36,000 DISCUSSANTS FOR AN EXCITING 5899 04:28:36,000 --> 04:28:37,520 DYNAMIC ELIMINATING FIRST DAY OF 5900 04:28:37,520 --> 04:28:39,080 TWO SESSIONS. 5901 04:28:39,080 --> 04:28:42,520 THEY REFLECTED IN THEIR TALKS 5902 04:28:42,520 --> 04:28:45,320 RAPID DEVELOPMENT OF SEVERAL 5903 04:28:45,320 --> 04:28:47,320 FIELDS AND INTERSECTION OF 5904 04:28:47,320 --> 04:28:49,480 COMMUTATION, AGING, SYSTEMS, 5905 04:28:49,480 --> 04:28:53,120 GENETICS, OMICS, IMAGING, 5906 04:28:53,120 --> 04:28:54,760 BIOLOGY, NEUROSCIENCE, MEDICINE 5907 04:28:54,760 --> 04:28:56,200 AND OTHER FIELDS. 5908 04:28:56,200 --> 04:28:59,200 WHILE THE CLUSTER BY THE TARGET 5909 04:28:59,200 --> 04:29:00,760 APPLICATIONS SYSTEM MANY 5910 04:29:00,760 --> 04:29:02,560 RESEARCH APPROACHES ARE LARGELY 5911 04:29:02,560 --> 04:29:05,240 INTER DISCIPLINARY. 5912 04:29:05,240 --> 04:29:09,280 LARGE VOLUMES OF GENERATED DATA 5913 04:29:09,280 --> 04:29:11,080 IN NECESSITATES MATTERS FOR 5914 04:29:11,080 --> 04:29:18,400 PREDICTIONS AND INTEGRATING IS 5915 04:29:18,400 --> 04:29:24,560 ESPECIALLY AND COULD BE THE 5916 04:29:24,560 --> 04:29:29,880 BUYICONTRIBUTION FORFIELDS AND L 5917 04:29:29,880 --> 04:29:32,240 LAYER OF PREDICTION AND 5918 04:29:32,240 --> 04:29:32,520 ANALYSIS. 5919 04:29:32,520 --> 04:29:34,800 WITH STEPS IN THE RIGHT 5920 04:29:34,800 --> 04:29:37,280 DIRECTION TOWARDS MORE ACCURATE 5921 04:29:37,280 --> 04:29:42,520 DESCRIPTION OF RE REAL WORLD 5922 04:29:42,520 --> 04:29:43,160 COMPLEXITY. 5923 04:29:43,160 --> 04:29:46,840 THIS COULD CREATE AGING AND 5924 04:29:46,840 --> 04:29:48,760 LONGEVITY AND PREVIOUSLY DEEMED 5925 04:29:48,760 --> 04:29:52,240 IMPOSSIBLE AND CONTRIBUTE TO A 5926 04:29:52,240 --> 04:29:53,640 STRATEGIC DIRECTIONS THROUGH A 5927 04:29:53,640 --> 04:29:56,920 BETTER UNDERSTANDING OF AGING 5928 04:29:56,920 --> 04:29:58,360 PROCESSES AND THEIR IMPACT ON 5929 04:29:58,360 --> 04:30:02,040 THE PREVENTION PROGNOSIS AND 5930 04:30:02,040 --> 04:30:02,320 LONGEVITY. 5931 04:30:02,320 --> 04:30:03,360 THANK YOU. 5932 04:30:03,360 --> 04:30:06,440 SO TOMORROW WE START AT 12:25 5933 04:30:06,440 --> 04:30:08,440 WITH SESSION 3. 5934 04:30:08,440 --> 04:30:10,000 COMPUTATIONAL ANALYSIS OF 5935 04:30:10,000 --> 04:30:13,480 COMPLEX BEHAVIOR. 5936 04:30:13,480 --> 04:30:15,520 >>THANK YOU, ALL. 5937 04:30:15,520 --> 04:30:25,840 SEE YOU TOMORROW.