1 00:00:05,760 --> 00:00:10,720 I AM WIN ARIAS, A SENIOR 2 00:00:10,720 --> 00:00:14,360 SCIENTIST EMERITUS AT THE 3 00:00:14,360 --> 00:00:16,320 NATIONAL INSTITUTES OF HEALTH IN 4 00:00:16,320 --> 00:00:17,200 BETHESDA, MARYLAND. 5 00:00:17,200 --> 00:00:21,080 AND WITH MY COLLEAGUE, DAN 6 00:00:21,080 --> 00:00:22,800 KASTNER, WHO IS OF THE HUMAN 7 00:00:22,800 --> 00:00:24,440 GENOME RESEARCH INSTITUTE HERE 8 00:00:24,440 --> 00:00:29,120 AT THE NIH, WE WELCOME YOU TO 9 00:00:29,120 --> 00:00:32,080 THE 11TH SESSION OF THE 23RD 10 00:00:32,080 --> 00:00:34,160 YEAR OF A COURSE CALLED 11 00:00:34,160 --> 00:00:37,120 DEMYSTIFYING MEDICINE. 12 00:00:37,120 --> 00:00:39,840 NOW THE GOAL OF THIS COURSE IS 13 00:00:39,840 --> 00:00:40,920 REALLY REPRESENTED BY THE LOGO 14 00:00:40,920 --> 00:00:43,440 IN THE UPPER RIGHT OF MY SLIDE, 15 00:00:43,440 --> 00:00:45,760 WHICH IS, TO MANY OF US IN THE 16 00:00:45,760 --> 00:00:46,960 EASTERN PART OF THE UNITED 17 00:00:46,960 --> 00:00:48,280 STATES, THE MOST FAMOUS BRIDGE 18 00:00:48,280 --> 00:00:50,360 IN THE WORLD, THE BROOKLYN 19 00:00:50,360 --> 00:00:51,560 BRIDGE. 20 00:00:51,560 --> 00:00:55,920 AND IT CONNECTS TWO SHORES: 21 00:00:55,920 --> 00:00:58,560 BROOKLYN AND MANHATTAN. 22 00:00:58,560 --> 00:01:00,200 AND THE TWO CHARACTERS ON THE 23 00:01:00,200 --> 00:01:03,800 BRIDGE CATWALK ARE DISCUSSING AS 24 00:01:03,800 --> 00:01:06,880 IN TODAY'S PRESENTATION THE 25 00:01:06,880 --> 00:01:10,480 STATUS OF REALLY NEUROBIOLOGY 26 00:01:10,480 --> 00:01:11,560 FROM THE LEVEL OF MOLECULES TO 27 00:01:11,560 --> 00:01:14,760 THE LEVEL OF PATIENTS. 28 00:01:14,760 --> 00:01:19,440 THE PURPOSE OF THIS COURSE IS TO 29 00:01:19,440 --> 00:01:20,840 BRING EXCITING DEVELOPMENTS IN 30 00:01:20,840 --> 00:01:22,040 BIOLOGY AND ENGINEERING WITH 31 00:01:22,040 --> 00:01:23,040 MEDICINE. 32 00:01:23,040 --> 00:01:25,120 IT'S AS IF WE ARE ALL LIVING IN 33 00:01:25,120 --> 00:01:28,320 A WORLD OF SILOS, WHERE PEOPLE 34 00:01:28,320 --> 00:01:30,920 ARE EXPERTS IN THEIR OWN AREA 35 00:01:30,920 --> 00:01:33,560 BUT NOT VERY MUCH AWARE, IF AT 36 00:01:33,560 --> 00:01:35,920 ALL AT TIMES, OF WHAT GOES ON, 37 00:01:35,920 --> 00:01:38,360 FOR EXAMPLE, IN A CLINICAL ARENA 38 00:01:38,360 --> 00:01:41,200 OR IN A BASIC LABORATORY. 39 00:01:41,200 --> 00:01:43,840 SO THE GOAL OF THIS COURSE IS TO 40 00:01:43,840 --> 00:01:48,200 EXCITE YOUR INTEREST, NOT TO 41 00:01:48,200 --> 00:01:49,600 OVERWHELM YOU WITH MASSIVE 42 00:01:49,600 --> 00:01:53,440 AMOUNTS OF INFORMATION. 43 00:01:53,440 --> 00:01:55,200 THIS IS NOT LAST WEEK'S RESEARCH 44 00:01:55,200 --> 00:01:55,880 SEMINAR. 45 00:01:55,880 --> 00:01:57,800 FREQUENTLY, WE HAVE LIVE 46 00:01:57,800 --> 00:01:59,360 PATIENTS WHO BEGIN BY TELLING 47 00:01:59,360 --> 00:02:04,200 SOMETHING ABOUT THEIR DISEASE TO 48 00:02:04,200 --> 00:02:04,600 PUT IT IN A CLINICAL FRAMEWORK. 49 00:02:04,600 --> 00:02:07,360 NOW, TODAY'S TOPIC WAS 50 00:02:07,360 --> 00:02:10,080 ORIGINALLY CALLED SOMETHING 51 00:02:10,080 --> 00:02:10,520 SIMPLE. 52 00:02:10,520 --> 00:02:12,120 HOW IS THE BRAIN ORGANIZED AND 53 00:02:12,120 --> 00:02:14,320 HOW DOES IT FUNCTION? 54 00:02:14,320 --> 00:02:17,040 NOW, TODAY, WE'RE NOT GOING TO 55 00:02:17,040 --> 00:02:20,200 ANSWER, OF COURSE, ALL OF THOSE 56 00:02:20,200 --> 00:02:21,640 QUESTIONS, BUT THE IDEA IS TO 57 00:02:21,640 --> 00:02:23,000 STIMULATE YOUR INTEREST AND TO 58 00:02:23,000 --> 00:02:25,800 LET YOU SHARE THE EXTRAORDINARY 59 00:02:25,800 --> 00:02:28,280 EXCITEMENT THAT IS GOING ON IN 60 00:02:28,280 --> 00:02:30,720 TWO SEPARATE BUT RELATED WORLDS 61 00:02:30,720 --> 00:02:35,640 OF UNDERSTANDING BRAIN FUNCTION. 62 00:02:35,640 --> 00:02:38,600 NOW, MANY YEARS AGO, ACTUALLY IN 63 00:02:38,600 --> 00:02:41,040 THE MID 19TH CENTURY, I GUESS, 64 00:02:41,040 --> 00:02:45,920 THE BRAIN WAS STATED BY RAMON 65 00:02:45,920 --> 00:02:52,280 CAJAL, THE NO THE NOBEL LAUREATE 66 00:02:52,280 --> 00:02:53,680 BRAIN IS A WORLD CONSISTING OF A 67 00:02:53,680 --> 00:02:56,880 NUMBER OF UNEXPLORED CONTINENTS 68 00:02:56,880 --> 00:02:58,720 AND GREAT STRETCHES OF UNKNOWN 69 00:02:58,720 --> 00:02:59,080 TERRITORY. 70 00:02:59,080 --> 00:03:01,800 IT IS STILL, TODAY, LARGELY 71 00:03:01,800 --> 00:03:03,080 UNEXPLORED, AND THERE ARE GREAT 72 00:03:03,080 --> 00:03:05,200 STRETCHES OF UNKNOWN TERRITORY 73 00:03:05,200 --> 00:03:10,440 WHICH WE WILL HEAR ABOUT. 74 00:03:10,440 --> 00:03:14,840 NOW, AS A BACKGROUND, PERMIT ME 75 00:03:14,840 --> 00:03:16,240 A VERY BRIEF HISTORY OF 76 00:03:16,240 --> 00:03:17,440 NEUROSCIENCE. 77 00:03:17,440 --> 00:03:19,160 IN ANTIQUITY, THINGS WERE 78 00:03:19,160 --> 00:03:22,240 LIMITED BY THE PRESENCE OF THE 79 00:03:22,240 --> 00:03:22,760 SKULL. 80 00:03:22,760 --> 00:03:24,760 AND ALTHOUGH THERE WERE 81 00:03:24,760 --> 00:03:25,640 OBSERVATIONS AS TO WHAT THE 82 00:03:25,640 --> 00:03:27,520 BRAIN LOOKED LIKE, GROSSLY, 83 00:03:27,520 --> 00:03:34,160 THERE WERE ALSO EVIDENCE FOR 84 00:03:34,160 --> 00:03:35,800 TREPHINING, THAT IS, THE MAKING 85 00:03:35,800 --> 00:03:37,560 OF HOLES IN THE SKULLS TO 86 00:03:37,560 --> 00:03:38,080 RELIEVE PRESSURE. 87 00:03:38,080 --> 00:03:39,520 BUT IT REALLY WASN'T UNTIL THE 88 00:03:39,520 --> 00:03:41,840 19TH AND 20TH CENTURY THAT 89 00:03:41,840 --> 00:03:43,240 NEUROLOGY AS A DISCIPLINE CAME 90 00:03:43,240 --> 00:03:46,360 INTO ITS OWN. 91 00:03:46,360 --> 00:03:47,320 AND THIS WAS DUE TO THE 92 00:03:47,320 --> 00:03:49,400 DESCRIPTION FOR THE FIRST TIME 93 00:03:49,400 --> 00:03:53,240 OF SIGNS, SYMPTOMS, PATHWAYS, 94 00:03:53,240 --> 00:03:58,360 LARGELY DEVELOPED OUT OF AUTOPSY 95 00:03:58,360 --> 00:03:59,640 STUDIES, AND ACTUALLY SOMETIMES 96 00:03:59,640 --> 00:04:01,000 FROM THE LOCALIZATION OF MOTOR 97 00:04:01,000 --> 00:04:03,720 FUNCTIONS BY STIMULATING AREAS 98 00:04:03,720 --> 00:04:05,720 OF THE BROCA REGION, FOR 99 00:04:05,720 --> 00:04:09,320 EXAMPLE, TO ASSOCIATE THOSE 100 00:04:09,320 --> 00:04:11,040 SPECIFIC AREAS WITH SPECIFIC 101 00:04:11,040 --> 00:04:16,960 MOTOR MOVEMENTS IN PARTS OF THE 102 00:04:16,960 --> 00:04:17,840 BODY. 103 00:04:17,840 --> 00:04:20,880 BUT IT WAS CHARCOT IN FRANCE 104 00:04:20,880 --> 00:04:22,080 CONSIDERED THE FATHER OF 105 00:04:22,080 --> 00:04:22,960 CLINICAL NEUROLOGY WHICH FOR 106 00:04:22,960 --> 00:04:24,600 MANY, MANY YEARS WAS ALMOST LIKE 107 00:04:24,600 --> 00:04:25,960 A DETECTIVE STORY, BECAUSE ONE 108 00:04:25,960 --> 00:04:32,040 HAD TO BE COMPETENT IN 109 00:04:32,040 --> 00:04:32,680 NEUROLOGIC EXAMINATION IN ORDER 110 00:04:32,680 --> 00:04:34,000 TO TRY AND DETERMINE WHERE, SAY, 111 00:04:34,000 --> 00:04:37,840 DEFECTS IN ONE OR TWO NEURONAL 112 00:04:37,840 --> 00:04:39,920 PATHWAYS OVERLAPPED, WHICH WOULD 113 00:04:39,920 --> 00:04:44,280 LOCALIZE WHERE PATHOLOGY MIGHT 114 00:04:44,280 --> 00:04:45,280 BE. 115 00:04:45,280 --> 00:04:47,040 IT WAS ALSO THE ERA OF 116 00:04:47,040 --> 00:04:48,240 PSYCHIATRY, AND FREUD, YOU MAY 117 00:04:48,240 --> 00:04:50,280 KNOW, STARTED OUT AS A 118 00:04:50,280 --> 00:04:51,520 NEUROSCIENTIST. 119 00:04:51,520 --> 00:04:55,040 AND IMPORTANTLY, IT WAS THE TIME 120 00:04:55,040 --> 00:04:57,760 WHEN NERVE CONDUCTION STUDIES OF 121 00:04:57,760 --> 00:05:00,360 ISOLATED NERVES OR IN DIFFERENT 122 00:05:00,360 --> 00:05:02,920 SPECIES ESTABLISHED MUCH OF THE 123 00:05:02,920 --> 00:05:05,400 PHYSIOLOGY AND BIOCHEMISTRY. 124 00:05:05,400 --> 00:05:07,800 AND THEN IN THE LATE 20TH 125 00:05:07,800 --> 00:05:10,120 CENTURY, THINGS REALLY CHANGED. 126 00:05:10,120 --> 00:05:12,120 WITH SUDDENLY THE ABILITY TO 127 00:05:12,120 --> 00:05:14,160 VISUALIZE THROUGH THE SKULL, 128 00:05:14,160 --> 00:05:15,680 USING IMAGING TECHNIQUES WHICH 129 00:05:15,680 --> 00:05:20,400 WE WILL HEAR ABOUT TODAY, AND 130 00:05:20,400 --> 00:05:21,920 ALSO THE DEVELOPMENT OF CELL 131 00:05:21,920 --> 00:05:23,120 BIOLOGIC TECHNIQUES, COUPLED 132 00:05:23,120 --> 00:05:25,320 WITH THE DISCOVERY OF 133 00:05:25,320 --> 00:05:27,200 NEUROTRANSMITTERS, THE ROLE OF 134 00:05:27,200 --> 00:05:29,360 GENETICS, CELL-BASED STUDIES, 135 00:05:29,360 --> 00:05:31,440 AND EVENTUALLY DRUGS AND SOME 136 00:05:31,440 --> 00:05:34,280 TREATMENTS THAT EMERGED. 137 00:05:34,280 --> 00:05:35,720 WHAT'S HAPPENING IN THE 21ST 138 00:05:35,720 --> 00:05:37,160 CENTURY? 139 00:05:37,160 --> 00:05:38,760 ONE MIGHT THINK THAT TECHNOLOGY 140 00:05:38,760 --> 00:05:41,160 AND BIOLOGY DEVELOPMENTS WILL 141 00:05:41,160 --> 00:05:45,400 CONTINUE TO INCREASE, MAYBE EVEN 142 00:05:45,400 --> 00:05:46,200 AT A FASTER RATE. 143 00:05:46,200 --> 00:05:48,800 WE NOW HAVE THE IMPACT OF 144 00:05:48,800 --> 00:05:50,680 VARIOUS OMICS. 145 00:05:50,680 --> 00:05:53,240 THE WONDER OF ORGANOIDS, AND 146 00:05:53,240 --> 00:05:54,640 COMPUTER INTERFACING. 147 00:05:54,640 --> 00:05:56,920 NOW DESPITE ALL OF THESE 148 00:05:56,920 --> 00:05:59,560 EXCITING ADVANCES, CONVERTING A 149 00:05:59,560 --> 00:06:02,600 COMPLETELY CLINICAL BEDSIDE 150 00:06:02,600 --> 00:06:05,920 BRANCH OF MEDICINE INTO A HIGHLY 151 00:06:05,920 --> 00:06:09,400 TECHNICAL AND PRECISE DIAGNOSTIC 152 00:06:09,400 --> 00:06:12,760 AND THERAPEUTIC AT TIMES 153 00:06:12,760 --> 00:06:14,200 FEATURE, IT STILL REMAINS THE 154 00:06:14,200 --> 00:06:16,600 BRAVE NEW WORLD, THE GREAT 155 00:06:16,600 --> 00:06:21,000 CHALLENGE, THE LAST FRONTIER. 156 00:06:21,000 --> 00:06:22,600 SO TODAY WE'RE EXTREMELY 157 00:06:22,600 --> 00:06:27,320 FORTUNATE IN HAVING TWO LEADERS 158 00:06:27,320 --> 00:06:33,040 IN DIFFERENT ASPECTS OF 159 00:06:33,040 --> 00:06:37,400 CONTEMPORARY NEUROSCIENCE. 160 00:06:37,400 --> 00:06:39,280 SO OUR FIRST SPEAKER IS GOING TO 161 00:06:39,280 --> 00:06:42,240 BE MARCUS RAICHLE, WHO DID HIS 162 00:06:42,240 --> 00:06:43,120 UNDERGRADUATE AND MEDICAL 163 00:06:43,120 --> 00:06:46,680 TRAINING AT THE UNIVERSITY OF 164 00:06:46,680 --> 00:06:47,680 WASHINGTON, RESIDENCY AT JOHNS 165 00:06:47,680 --> 00:06:49,360 HOPKINS, AND THEN IN NEUROLOGY 166 00:06:49,360 --> 00:06:50,640 AT CORNEL. 167 00:06:50,640 --> 00:06:53,400 AND THEN HE SPENT MANY YEARS AT 168 00:06:53,400 --> 00:06:54,880 WASHINGTON UNIVERSITY IN 169 00:06:54,880 --> 00:06:57,960 ST. LOUIS, WHERE CURRENTLY, HE'S 170 00:06:57,960 --> 00:06:59,160 THE WOLF DISTINGUISHED PROFESSOR 171 00:06:59,160 --> 00:07:02,240 OF MEDICINE, AND ALSO PROFESSOR 172 00:07:02,240 --> 00:07:05,080 OF RADIOLOGY, NEUROLOGY, 173 00:07:05,080 --> 00:07:06,920 NEUROBIOLOGY, AND BIOMEDICAL 174 00:07:06,920 --> 00:07:11,680 ENGINEERING. 175 00:07:11,680 --> 00:07:13,000 HE IS ACKNOWLEDGED TO HAVE 176 00:07:13,000 --> 00:07:14,320 PLAYED A MAJOR ROLE IN THE 177 00:07:14,320 --> 00:07:18,160 DEVELOPMENT OF FUNCTIONAL 178 00:07:18,160 --> 00:07:19,640 IMAGING, PARTICULARLY FUNCTIONAL 179 00:07:19,640 --> 00:07:22,720 MAGNETIC RESONANCE IMAGING, 180 00:07:22,720 --> 00:07:24,800 FMRI, AND POSITRON EMISSION 181 00:07:24,800 --> 00:07:27,080 TOMOGRAPHY, OR PET SCANNING, TO 182 00:07:27,080 --> 00:07:29,480 STUDY THE HUMAN BRAIN 183 00:07:29,480 --> 00:07:31,280 ORGANIZATION AND HOW IT 184 00:07:31,280 --> 00:07:35,000 FUNCTIONS IN HEALTH AND DISEASE. 185 00:07:35,000 --> 00:07:36,520 FOR THESE POWERFUL TOOLS AND THE 186 00:07:36,520 --> 00:07:38,880 DEVELOPMENT OF THEM, HE HAS 187 00:07:38,880 --> 00:07:41,720 RECEIVED A LARGE NUMBER OF 188 00:07:41,720 --> 00:07:42,160 RECOGNITIONS. 189 00:07:42,160 --> 00:07:43,840 FOR EXAMPLE, HE'S A MEMBER OF 190 00:07:43,840 --> 00:07:46,000 THE NATIONAL ACADEMIES OF 191 00:07:46,000 --> 00:07:48,560 SCIENCE, OF MEDICINE, AND THE 192 00:07:48,560 --> 00:07:53,000 ACADEMY OF ARTS AND SCIENCES. 193 00:07:53,000 --> 00:07:55,320 HE'S RECEIVED NUMEROUS 194 00:07:55,320 --> 00:07:56,360 PRESTIGIOUS NATIONAL AND 195 00:07:56,360 --> 00:07:57,800 INTERNATIONAL AWARDS, 196 00:07:57,800 --> 00:07:58,800 HONORARY DEGREES, AND MANY 197 00:07:58,800 --> 00:08:01,120 PRIZES, MAINLY IN NEUROSCIENCE, 198 00:08:01,120 --> 00:08:04,720 AND WAS THE INAUGURAL CARL AND 199 00:08:04,720 --> 00:08:07,240 GERTY CORI AWARD RECIPIENT FOR 200 00:08:07,240 --> 00:08:08,160 FACULTY ACHIEVEMENT AT 201 00:08:08,160 --> 00:08:14,680 WASHINGTON UNIVERSITY. 202 00:08:14,680 --> 00:08:16,640 OUR SECOND SPEAKER IS NELSON 203 00:08:16,640 --> 00:08:18,400 SPRUSTON. 204 00:08:18,400 --> 00:08:20,480 HE DID HIS UNDERGRADUATE WORK IN 205 00:08:20,480 --> 00:08:22,760 PHYSIOLOGY AT THE UNIVERSITY OF 206 00:08:22,760 --> 00:08:24,600 BRITISH COLUMBIA, RECEIVED A 207 00:08:24,600 --> 00:08:28,680 PH.D. IN NEUROSCIENCE AT BAYLOR 208 00:08:28,680 --> 00:08:31,080 COLLEGE OF MEDICINE, FOLLOWED BY 209 00:08:31,080 --> 00:08:33,600 A POSTDOCTORAL FELLOWSHIP IN 210 00:08:33,600 --> 00:08:34,920 HEIDELBERG AT THE MAX PLANCK 211 00:08:34,920 --> 00:08:37,080 INSTITUTE FOR MEDICAL RESEARCH. 212 00:08:37,080 --> 00:08:38,720 FOR THE NEXT 16 YEARS, HE WAS ON 213 00:08:38,720 --> 00:08:42,880 THE FACULTY AT THE NORTHWESTERN 214 00:08:42,880 --> 00:08:43,520 UNIVERSITY SCHOOL OF MEDICINE. 215 00:08:43,520 --> 00:08:47,280 AND IN 2011, WAS RECRUITED TO 216 00:08:47,280 --> 00:08:50,440 THE HOWARD HUGHES MEDICAL 217 00:08:50,440 --> 00:08:54,360 INSTITUTE JANELIA CENTER, WHERE 218 00:08:54,360 --> 00:08:55,920 HE IS SENIOR DIRECTOR OF 219 00:08:55,920 --> 00:08:58,320 SCIENTIFIC PROGRAMS. 220 00:08:58,320 --> 00:09:00,480 HIS MAIN RESEARCH IS ON THE ROLE 221 00:09:00,480 --> 00:09:03,440 OF THE HIPPOCAMPUS AND 222 00:09:03,440 --> 00:09:05,320 MECHANISMS FOR CIRCUIT 223 00:09:05,320 --> 00:09:06,760 FORMATION, WHICH MEDIATE 224 00:09:06,760 --> 00:09:09,680 LEARNING AND MEMORY. 225 00:09:09,680 --> 00:09:12,320 FOR HIS WORK, HE'S RECEIVED A 226 00:09:12,320 --> 00:09:13,640 NATIONAL SCIENCE FOUNDATION 227 00:09:13,640 --> 00:09:15,040 CAREER AWARD, AND A 228 00:09:15,040 --> 00:09:16,480 DISTINGUISHED INVESTIGATOR AWARD 229 00:09:16,480 --> 00:09:19,200 OF THE BRAIN AND BEHAVIOR 230 00:09:19,200 --> 00:09:21,160 FOUNDATION. 231 00:09:21,160 --> 00:09:23,040 WE ARE EXTREMELY PLEASED TO HAVE 232 00:09:23,040 --> 00:09:26,320 BOTH OF YOU GENTLEMEN WITH US 233 00:09:26,320 --> 00:09:30,000 TODAY TO DISCUSS TWO SOMEWHAT 234 00:09:30,000 --> 00:09:32,200 DIFFERENT BUT INTERRELATED 235 00:09:32,200 --> 00:09:34,280 ASPECTS OF THE EXCITING 236 00:09:34,280 --> 00:09:36,480 DEVELOPMENT IN THE FIELD OF 237 00:09:36,480 --> 00:09:37,600 NEUROSCIENCE, WHICH WILL TEACH 238 00:09:37,600 --> 00:09:40,600 US MORE AND MORE ABOUT HOW THE 239 00:09:40,600 --> 00:09:44,360 BRAIN IS ORGANIZED AND HOW IT 240 00:09:44,360 --> 00:09:45,120 WORKS. 241 00:09:45,120 --> 00:09:47,960 SO MARCOS, WOULD YOU PLEASE 242 00:09:47,960 --> 00:09:53,000 BEGIN AS THE FIRST SPEAKER. 243 00:09:53,000 --> 00:09:56,480 MARCUS. 244 00:09:56,480 --> 00:09:57,680 >>I WOULD LIKE TO MAYBE SHARE 245 00:09:57,680 --> 00:10:01,760 YOU A BIT OF HISTORY OF HOW THE 246 00:10:01,760 --> 00:10:03,480 WORLD IN WHICH I LIVE HAS 247 00:10:03,480 --> 00:10:05,120 DEVELOPED OVER TIME AND WHAT 248 00:10:05,120 --> 00:10:08,720 MOTIVATES IT PRESENTLY. 249 00:10:08,720 --> 00:10:10,720 I WOULD SAY THE MOST MOTIVATING 250 00:10:10,720 --> 00:10:12,040 ASPECT OF IT IS APPEARING ON 251 00:10:12,040 --> 00:10:17,600 THIS SLIDE IN FRONT OF YOU NOW. 252 00:10:17,600 --> 00:10:18,920 ON THE LEFT YOU HAVE A PICTURE 253 00:10:18,920 --> 00:10:23,360 OF THE HUMAN BODY FROM THE LEGS 254 00:10:23,360 --> 00:10:25,440 UP WHERE THERE IS A PET SCAN AND 255 00:10:25,440 --> 00:10:27,760 AN MR SCAN SUPERIMPOSED, AND I 256 00:10:27,760 --> 00:10:29,160 THINK IT IS PRETTY OBVIOUS THAT 257 00:10:29,160 --> 00:10:31,720 THE BRAIN STANDS OUT. 258 00:10:31,720 --> 00:10:35,720 AND THIS IS A MEASURE OF ITS 259 00:10:35,720 --> 00:10:36,360 METABOLISM. 260 00:10:36,360 --> 00:10:39,240 IN THIS CASE, ITS METABOLIC RATE 261 00:10:39,240 --> 00:10:39,680 FOR GLUCOSE. 262 00:10:39,680 --> 00:10:41,480 WHILE THE BRAIN IS ONLY 2% OF 263 00:10:41,480 --> 00:10:45,960 THE BODY WEIGHT, IT CONSUMES 20% 264 00:10:45,960 --> 00:10:47,680 OF THE ENERGY BUDGET FOR THE 265 00:10:47,680 --> 00:10:48,640 HUMAN BODY. 266 00:10:48,640 --> 00:10:53,440 SO IT'S 10 TIMES MORE EXPENSIVE 267 00:10:53,440 --> 00:10:54,960 PER UNIT WEIGHT THAN YOU WOULD 268 00:10:54,960 --> 00:10:57,600 HAVE ANTICIPATED. 269 00:10:57,600 --> 00:10:59,240 SO THE ISSUE THAT'S ON THE TABLE 270 00:10:59,240 --> 00:11:01,320 TODAY, AND IT'S ON MY -- AT THE 271 00:11:01,320 --> 00:11:05,600 TOP OF MY LIST, IS TO UNDERSTAND 272 00:11:05,600 --> 00:11:06,920 WHY IS THE BRAIN SO EXPENSIVE? 273 00:11:06,920 --> 00:11:08,880 WHERE IS THE MONEY GOING HERE, 274 00:11:08,880 --> 00:11:10,400 AND HOW SHOULD WE THINK ABOUT 275 00:11:10,400 --> 00:11:11,400 THIS? 276 00:11:11,400 --> 00:11:18,160 SO IF WE CAN HAVE THE NEXT 277 00:11:18,160 --> 00:11:19,760 SLIDE, THIS WAS AN EXPERIMENT 278 00:11:19,760 --> 00:11:21,320 THAT WAS OVERLOOKED FOR A GOOD 279 00:11:21,320 --> 00:11:25,440 BIT OF TIME, BUT IT USES THE 280 00:11:25,440 --> 00:11:26,280 FIRST TECHNIQUE THAT WAS 281 00:11:26,280 --> 00:11:29,000 AVAILABLE WHERE WE COULD 282 00:11:29,000 --> 00:11:31,080 ACTUALLY HAVE A MEASUREMENT OF 283 00:11:31,080 --> 00:11:33,040 THESE METABOLIC STATES OF THE 284 00:11:33,040 --> 00:11:33,400 BRAIN. 285 00:11:33,400 --> 00:11:36,400 IN THIS CASE, IT'S OXYGEN 286 00:11:36,400 --> 00:11:37,640 CONSUMPTION AND IT'S BLOOD FLOW, 287 00:11:37,640 --> 00:11:42,240 AND THIS WAS THE WORK OF SEYMOUR 288 00:11:42,240 --> 00:11:45,480 SAN FRANCISCO KETY AND CARL 289 00:11:45,480 --> 00:11:45,960 SCHMIDT. 290 00:11:45,960 --> 00:11:50,000 IT'S STILL THE PRIMARY MEANS OF 291 00:11:50,000 --> 00:11:50,840 UNARGUABLY MEASURING HOW MUCH 292 00:11:50,840 --> 00:11:52,720 ENERGY IS BEING CONSUMED BY THE 293 00:11:52,720 --> 00:11:55,120 BRAIN. 294 00:11:55,120 --> 00:11:57,120 SO IF I CAN HAVE THE NEXT CLICK 295 00:11:57,120 --> 00:12:01,040 ON THIS SLIDE. 296 00:12:01,040 --> 00:12:02,080 THIS GROUP ASKED THE QUESTION, 297 00:12:02,080 --> 00:12:05,200 WHAT IS THE EFFECT OF AN 298 00:12:05,200 --> 00:12:08,680 EXTREMELY DIFFICULT MENTAL 299 00:12:08,680 --> 00:12:10,560 ARITHMETIC TASK ON THE 300 00:12:10,560 --> 00:12:12,840 CIRCULATION AND METABOLISM OF 301 00:12:12,840 --> 00:12:13,520 THE HUMAN BRAIN. 302 00:12:13,520 --> 00:12:16,040 AND THIS WAS PUBLISHED IN 1955. 303 00:12:16,040 --> 00:12:18,760 IT'S RARELY CITED. 304 00:12:18,760 --> 00:12:20,840 BUT THE SIGNIFICANT FEATURE OF 305 00:12:20,840 --> 00:12:22,040 THIS EXPERIMENT WAS THE FACT 306 00:12:22,040 --> 00:12:25,760 THAT EVEN THOUGH THERE WERE 307 00:12:25,760 --> 00:12:27,640 CHANGES IN THE 308 00:12:27,640 --> 00:12:28,520 ELECTROENCEPHALOGRAM, THERE WERE 309 00:12:28,520 --> 00:12:30,800 CHANGES IN BLOOD PRESSURE, THERE 310 00:12:30,800 --> 00:12:33,160 WERE NO CHANGES FOR THE WHOLE 311 00:12:33,160 --> 00:12:35,960 BRAIN IN ITS BLOOD FLOW AND ITS 312 00:12:35,960 --> 00:12:37,360 OXYGEN CONSUMPTION AND SOME 313 00:12:37,360 --> 00:12:39,200 OTHER THINGS THAT WERE DERIVED 314 00:12:39,200 --> 00:12:41,160 FROM THAT. 315 00:12:41,160 --> 00:12:43,160 GIVEN THE FACT THAT THIS IS SUCH 316 00:12:43,160 --> 00:12:46,640 AN EXPENSIVE ORGAN, ONE MIGHT 317 00:12:46,640 --> 00:12:47,760 WELL HAVE IMAGINED IT WOULD BE 318 00:12:47,760 --> 00:12:49,920 VERY COSTLY DO THE KIND OF 319 00:12:49,920 --> 00:12:51,800 TASKS, BUT IF YOU CAN SHOW THE 320 00:12:51,800 --> 00:13:02,280 NEXT SLIDE, THE COST OF THAT 321 00:13:04,520 --> 00:13:06,040 ADDITIONAL MENTAL ACTIVITY WAS A 322 00:13:06,040 --> 00:13:06,600 TRIVIAL ADDITION. 323 00:13:06,600 --> 00:13:08,320 SO THE QUESTION IS HOW DO WE GET 324 00:13:08,320 --> 00:13:13,000 FROM THIS POINT, THIS SURPRISING 325 00:13:13,000 --> 00:13:14,320 FINDING, TO A BETTER 326 00:13:14,320 --> 00:13:17,480 UNDERSTANDING OF THIS? 327 00:13:17,480 --> 00:13:20,440 AND THE THING THAT WAS SO DEEPLY 328 00:13:20,440 --> 00:13:21,640 IMPORTANT IN THIS THING BOTH 329 00:13:21,640 --> 00:13:23,720 FROM A SCIENTIFIC POINT OF VIEW 330 00:13:23,720 --> 00:13:26,040 AND JUST THE CLINICAL ASPECTS OF 331 00:13:26,040 --> 00:13:30,080 THIS, WAS THE INVENTION OF X-RAY 332 00:13:30,080 --> 00:13:35,520 COMPUTED TOMOGRAPHY, LARGELY BY 333 00:13:35,520 --> 00:13:38,000 GODFREY HOUNSFIELD IN ENGLAND. 334 00:13:38,000 --> 00:13:40,800 THIS WAS IN 1973, AND AS A BODY 335 00:13:40,800 --> 00:13:42,160 NEUROLOGIST WHO HAD TO DEAL WITH 336 00:13:42,160 --> 00:13:44,200 MUCH CRUDER WAYS OF GETTING A 337 00:13:44,200 --> 00:13:46,480 LOOK AT THE BRAIN, THIS WAS 338 00:13:46,480 --> 00:13:48,360 TRULY REVOLUTIONARY FROM A 339 00:13:48,360 --> 00:13:57,200 CLINICAL POINT OF VIEW. 340 00:13:57,200 --> 00:13:59,040 AT ABOUT THE SAME TIME, I HAD 341 00:13:59,040 --> 00:14:04,720 GONE TO ST. LOUIS TO LOOK AT 342 00:14:04,720 --> 00:14:07,040 BRAIN CIRCULATION AND METABOLISM 343 00:14:07,040 --> 00:14:10,880 AT THE INVITATION OF MICHELLE 344 00:14:10,880 --> 00:14:12,520 TERPIGOSIAN, ONE OF THE PIONEERS 345 00:14:12,520 --> 00:14:16,040 IN THE WORLD IN THE USE OF 346 00:14:16,040 --> 00:14:18,960 CYCLOTRON ISOTOPES FOR BIOLOGY 347 00:14:18,960 --> 00:14:20,400 IN MEDICINE AND WAS DEEPLY 348 00:14:20,400 --> 00:14:21,680 INTERESTED IN DEVELOPING 349 00:14:21,680 --> 00:14:22,440 SOMETHING FOR THE BRAIN. 350 00:14:22,440 --> 00:14:25,640 ONE OF THE THINGS THAT ATTRACTED 351 00:14:25,640 --> 00:14:32,520 ME TO ST. LOUIS WAS TH BUILT ME 352 00:14:32,520 --> 00:14:35,120 WHAT THEY CALL A CHICKEN, 353 00:14:35,120 --> 00:14:36,680 RADIOACTIVE DETECTORS SITUATED 354 00:14:36,680 --> 00:14:39,720 AROUND THE HEAD OF A SUBJECT IN 355 00:14:39,720 --> 00:14:40,520 AN ANGIOGRAM SUITE. 356 00:14:40,520 --> 00:14:46,360 FOR PATIENTS THAT WERE HAVING 357 00:14:46,360 --> 00:14:47,520 ANGIOGRAPHY STUDIES DONE, WE 358 00:14:47,520 --> 00:14:49,800 WERE ALLOWED TO INJECT THESE 359 00:14:49,800 --> 00:14:51,000 ISOTOPES AND GET A PICTURE OF 360 00:14:51,000 --> 00:14:53,840 THE BRAIN. 361 00:14:53,840 --> 00:14:55,400 WHAT YOU COULD ONLY IMAGINE HOW 362 00:14:55,400 --> 00:15:00,080 CRUDE SUCH A PICTURE WOULD BE. 363 00:15:00,080 --> 00:15:03,040 BUT THE DEVELOPMENT OF CT WAS AN 364 00:15:03,040 --> 00:15:05,560 UNBELIEVABLE STIMULUS TO MOVE 365 00:15:05,560 --> 00:15:10,480 FORWARD WITH HOW WE DO THIS. 366 00:15:10,480 --> 00:15:14,880 SO THIS 26 PROBE SYSTEM WE HAD, 367 00:15:14,880 --> 00:15:17,280 THE SO-CALLED CHICKEN OVER HERE, 368 00:15:17,280 --> 00:15:18,920 WAS IMMEDIATELY DISASSEMBLED AND 369 00:15:18,920 --> 00:15:20,880 LAID OUT ON A TABLE WHERE YOU 370 00:15:20,880 --> 00:15:27,200 HAVE RADIOACTIVE DETECTORS 371 00:15:27,200 --> 00:15:28,080 CIRCLING AROUND AN OBJECT THAT 372 00:15:28,080 --> 00:15:29,720 WOULD HAVE RADIOACTIVITY IN IT, 373 00:15:29,720 --> 00:15:31,480 AND THE QUESTION WAS, COULD WE 374 00:15:31,480 --> 00:15:35,360 GET A SLICE THROUGH THERE AS YOU 375 00:15:35,360 --> 00:15:39,040 GET WITH CT. 376 00:15:39,040 --> 00:15:40,680 AND GET AN IMAGE OF WHAT'S GOING 377 00:15:40,680 --> 00:15:41,760 ON IN THERE. 378 00:15:41,760 --> 00:15:45,280 SO THIS LED FROM THIS TABLETOP 379 00:15:45,280 --> 00:15:51,080 THING THAT WE CALLED PETT I, OR 380 00:15:51,080 --> 00:15:56,320 PETT II, TO AN ACTUAL TOMORROW 381 00:15:56,320 --> 00:15:59,040 TOMOGRAPHIC SYSTEM BUILT OUTSIDE 382 00:15:59,040 --> 00:16:01,440 MY OFFICE BY THE ENGINEERING 383 00:16:01,440 --> 00:16:02,200 PEOPLE AT THE WASHINGTON 384 00:16:02,200 --> 00:16:02,760 UNIVERSITY CAMPUS. 385 00:16:02,760 --> 00:16:05,920 WE HAD SEVERAL OF THESE UP TO 386 00:16:05,920 --> 00:16:09,760 PETT IV AND PETT VI AND THEY 387 00:16:09,760 --> 00:16:11,840 BECAME EVER MORE VALUABLE. 388 00:16:11,840 --> 00:16:13,280 WHAT IT DID WAS ALLOW US TO DO 389 00:16:13,280 --> 00:16:15,560 FOR THE FIRST TIME EVER 390 00:16:15,560 --> 00:16:17,200 RADIOGRAPHY OF THE HUMAN BRAIN 391 00:16:17,200 --> 00:16:17,960 WITHOUT REMOVING THE BRAIN, 392 00:16:17,960 --> 00:16:19,680 SLICING IT UP AND LAYING IT ON 393 00:16:19,680 --> 00:16:20,280 X-RAY FILMS. 394 00:16:20,280 --> 00:16:21,360 SO THERE WERE A LOT OF THINGS 395 00:16:21,360 --> 00:16:22,440 THAT WERE OF INTEREST TO US. 396 00:16:22,440 --> 00:16:29,000 SO IF I MAY HAVE THE NEXT SLIDE. 397 00:16:29,000 --> 00:16:30,080 THE ISSUE WAS, IF YOU'RE GOING 398 00:16:30,080 --> 00:16:33,040 TO APPROACH THE BRAIN, HOW DO 399 00:16:33,040 --> 00:16:34,720 YOU BEGIN TO INTERROGATE WHAT 400 00:16:34,720 --> 00:16:41,160 IT'S DOING? 401 00:16:41,160 --> 00:16:43,560 AND AT THE INSISTENCE OF A MAJOR 402 00:16:43,560 --> 00:16:45,640 DONOR AT WASHINGTON UNIVERSITY, 403 00:16:45,640 --> 00:16:48,480 JAMES MCDONALD, THE DEVELOPER OF 404 00:16:48,480 --> 00:16:50,680 THE MCDONALD DOUGLAS AIRCRAFT 405 00:16:50,680 --> 00:16:52,440 COMPANY, HE INSISTED IF HE WAS 406 00:16:52,440 --> 00:16:54,080 GOING TO GIVE US SOME MONEY, 407 00:16:54,080 --> 00:16:56,240 THAT WE GET A GOOD PSYCHOLOGIST 408 00:16:56,240 --> 00:16:58,320 INVOLVED IN THIS UNDERTAKING, SO 409 00:16:58,320 --> 00:17:00,040 THAT WE UNDERSTOOD THE BEHAVIOR 410 00:17:00,040 --> 00:17:05,960 WE WERE TRYING TO EXPLAIN SO 411 00:17:05,960 --> 00:17:07,840 MIKE POSNER JOINED THIS GROUP, 412 00:17:07,840 --> 00:17:09,040 WHICH WAS A MAJOR STEP FORWARD 413 00:17:09,040 --> 00:17:10,400 IN HOW WE ACTUALLY DESIGNED 414 00:17:10,400 --> 00:17:12,120 EXPERIMENTS TO LOOK AT HOW THE 415 00:17:12,120 --> 00:17:19,640 BRAIN FUNCTIONS. 416 00:17:19,640 --> 00:17:21,280 THE STRATEGY THAT DEVELOPED WAS 417 00:17:21,280 --> 00:17:22,160 A KIND OF LEVEL OF 418 00:17:22,160 --> 00:17:22,480 INVESTIGATION. 419 00:17:22,480 --> 00:17:23,920 SO THE FIRST LEVEL, YOU JUST 420 00:17:23,920 --> 00:17:24,680 HAVE SOMEBODY LOOKING AT THE 421 00:17:24,680 --> 00:17:26,440 SCREEN WITH A CROSSHAIR ON IT 422 00:17:26,440 --> 00:17:28,080 AND YOU'D GET A PICTURE OF THAT. 423 00:17:28,080 --> 00:17:29,840 AND THEN WHAT YOU MIGHT DO FOR 424 00:17:29,840 --> 00:17:31,360 THE SECOND LEVEL WAS TO PUT A 425 00:17:31,360 --> 00:17:33,160 WORD ON THE SCREEN AND PEOPLE 426 00:17:33,160 --> 00:17:35,600 JUST LOOKED AT IT AND WE GOT 427 00:17:35,600 --> 00:17:39,880 ANOTHER PICTURE. 428 00:17:39,880 --> 00:17:41,080 THEN WE HAD PEOPLE SAY THE WORD 429 00:17:41,080 --> 00:17:42,600 AND FINALLY WE HAD THEM TO 430 00:17:42,600 --> 00:17:45,240 PROVIDE US WITH A VERB THAT 431 00:17:45,240 --> 00:17:46,800 WORKED FOR THE NOUN. 432 00:17:46,800 --> 00:17:48,520 SO IF YOU SAW A HAMMER, YOU 433 00:17:48,520 --> 00:17:54,000 MIGHT SAY POUND. 434 00:17:54,000 --> 00:17:56,280 WITH EACH INSTANCE OF THIS, WE 435 00:17:56,280 --> 00:17:57,280 SUBTRACTED THE PRECEDING 436 00:17:57,280 --> 00:17:58,320 ACTIVITY FROM THAT, SO WE HAD 437 00:17:58,320 --> 00:18:03,840 KIND OF A STAGED OPERATION HERE 438 00:18:03,840 --> 00:18:04,520 LOOKING AT THIS. 439 00:18:04,520 --> 00:18:06,120 IF YOU CAN SHOW THE NEXT SLIDE, 440 00:18:06,120 --> 00:18:07,680 SOMEHOW OR OTHER, NATURE GOT 441 00:18:07,680 --> 00:18:10,160 WIND OF WHAT WE WERE UP TO AND 442 00:18:10,160 --> 00:18:11,720 ACTUALLY IT'S THE ONLY TIME IN 443 00:18:11,720 --> 00:18:14,240 MY ENTIRE CAREER THAT NATURE HAS 444 00:18:14,240 --> 00:18:16,760 EVER INVITED US TO SUBMIT -- 445 00:18:16,760 --> 00:18:19,680 THEY'VE MADE UP FOR THAT BY 446 00:18:19,680 --> 00:18:22,440 REJECTING ME ON A REGULAR BASIS. 447 00:18:22,440 --> 00:18:25,840 BUT THIS APPEARED IN NATURE IN 448 00:18:25,840 --> 00:18:30,880 1988, THE CULMINATION OF THAT 449 00:18:30,880 --> 00:18:31,840 EXPERIMENT, AND IT HAS APPEARED 450 00:18:31,840 --> 00:18:33,360 IN TEXTBOOKS AND SO FORTH. 451 00:18:33,360 --> 00:18:34,240 IT'S A VERY NICE DEMONSTRATION 452 00:18:34,240 --> 00:18:39,360 OF WHAT WE WERE ABLE TO DO. 453 00:18:39,360 --> 00:18:40,440 BUT IT LEFT THE BACKGROUND OF 454 00:18:40,440 --> 00:18:41,800 THIS STUDY COMPLETELY ABSENT 455 00:18:41,800 --> 00:18:43,560 BECAUSE WE WERE VERY CLEVER AT 456 00:18:43,560 --> 00:18:48,440 SUBTRACTING OUT THE DIFFERENCES. 457 00:18:48,440 --> 00:18:50,200 BUT WE SIMPLY DIDN'T CONSIDER 458 00:18:50,200 --> 00:18:54,240 WHAT WAS GOING ON IN THE 459 00:18:54,240 --> 00:18:54,680 BACKGROUND. 460 00:18:54,680 --> 00:19:00,160 BUT AT THAT BECAME MORE 461 00:19:00,160 --> 00:19:01,480 APPARENT, THESE ARE THE UMAGES 462 00:19:01,480 --> 00:19:05,880 IMAGESOF THE FOUR DIFFERENT STAF 463 00:19:05,880 --> 00:19:08,040 BLOOD FLOW TO THE HUMAN BRAIN. 464 00:19:08,040 --> 00:19:09,360 I CHALLENGE YOU TO FIND ANY 465 00:19:09,360 --> 00:19:10,160 SIGNIFICANT DIFFERENCES AS YOU 466 00:19:10,160 --> 00:19:14,400 LOOK AT THE ACTUAL DATA THAT 467 00:19:14,400 --> 00:19:16,640 GENERATED THESE PRECEDING 468 00:19:16,640 --> 00:19:19,760 IMAGES. 469 00:19:19,760 --> 00:19:22,600 THESE ARE THE DIFFERENCE IMAGES, 470 00:19:22,600 --> 00:19:25,120 AND YOU CAN SEE THAT THOSE 471 00:19:25,120 --> 00:19:26,640 DIFFERENCES ARE ACTUALLY QUITE 472 00:19:26,640 --> 00:19:27,200 SMALL. 473 00:19:27,200 --> 00:19:29,600 I'M NOT SOMETHING THEY AREN'T 474 00:19:29,600 --> 00:19:32,240 IMPORTANT, BUT THEY ARE MAKING A 475 00:19:32,240 --> 00:19:34,400 SMALL DIFFERENCE IN THE ACTUAL 476 00:19:34,400 --> 00:19:36,040 OVERALL COST OF RUNNING THE 477 00:19:36,040 --> 00:19:37,280 BRAIN. 478 00:19:37,280 --> 00:19:41,840 SO WE HAVE HIDDEN UNDERNEATH ALL 479 00:19:41,840 --> 00:19:43,920 OF THIS AN ENORMOUS AMOUNT OF 480 00:19:43,920 --> 00:19:44,720 SOMETHING GOING ON AND THE 481 00:19:44,720 --> 00:19:46,880 QUESTION IS, WHAT IS IT, HOW DO 482 00:19:46,880 --> 00:19:53,800 WE THINK ABOUT THIS. 483 00:19:53,800 --> 00:19:55,840 SO THE TAKEAWAY AT THIS POINT IS 484 00:19:55,840 --> 00:19:57,120 HOW INFLUENTIAL ARE CHANGES IN 485 00:19:57,120 --> 00:20:00,120 THE CELLULAR ACTIVITY TO THE 486 00:20:00,120 --> 00:20:01,440 BRAIN'S ENORMOUS ENERGY 487 00:20:01,440 --> 00:20:02,120 CONSUMPTION ONGOING AT ALL 488 00:20:02,120 --> 00:20:02,960 TIMES. 489 00:20:02,960 --> 00:20:05,120 AND THE ANSWER IS VERY LITTLE. 490 00:20:05,120 --> 00:20:07,280 OVERALL. 491 00:20:07,280 --> 00:20:10,600 SO HOW DO WE GO FORWARD WITH 492 00:20:10,600 --> 00:20:16,840 THIS SORT OF PROBLEM? 493 00:20:16,840 --> 00:20:18,600 ONE OF THE ASSUMPTIONS THAT YOU 494 00:20:18,600 --> 00:20:20,560 HAVE IN DOING THIS KIND OF AN 495 00:20:20,560 --> 00:20:22,320 EXPERIMENT IS THAT YOUR CONTROL 496 00:20:22,320 --> 00:20:24,960 STATE IS NOT AFFECTED BY WHAT 497 00:20:24,960 --> 00:20:28,120 YOU ADD IN THE TASK STATE. 498 00:20:28,120 --> 00:20:32,040 THIS IS CALLED THE NOTION OF 499 00:20:32,040 --> 00:20:32,800 PURE INSERTION. 500 00:20:32,800 --> 00:20:35,760 THE QUESTION WAS, HAVE WE MADE 501 00:20:35,760 --> 00:20:37,520 SOME FALSE ASSUMPTION IN HOW ALL 502 00:20:37,520 --> 00:20:38,920 THIS WORKS? 503 00:20:38,920 --> 00:20:41,120 AND SO THE WAY TO CHECK ON THAT 504 00:20:41,120 --> 00:20:43,280 TO FIND OUT WHAT HAPPENS TO THE 505 00:20:43,280 --> 00:20:44,720 BASELINE IF YOU HAD A TASK ON 506 00:20:44,720 --> 00:20:47,360 TOP OF IT, IS YOU JUST REVERSED 507 00:20:47,360 --> 00:20:49,000 THESE SUBTRACTIONS. 508 00:20:49,000 --> 00:20:53,920 AND SEE WHAT HAPPENS. 509 00:20:53,920 --> 00:20:56,680 IF YOU' PURE INSERTION WORKS, YU 510 00:20:56,680 --> 00:20:57,320 SHOULD SEE NOTHING. 511 00:20:57,320 --> 00:21:06,480 BUT THAT IS NOT WHAT HAPPENED. 512 00:21:06,480 --> 00:21:10,040 THESE ARE THE DECREASES THAT 513 00:21:10,040 --> 00:21:11,520 OCCUR ROUTINELY IF YOU DO ANY 514 00:21:11,520 --> 00:21:14,720 EXPERIMENT OF THIS SORT. 515 00:21:14,720 --> 00:21:17,440 AND WHAT WAS SO EERIE ABOUT IT 516 00:21:17,440 --> 00:21:22,560 WAS HOW CONSISTENT THIS WAS. 517 00:21:22,560 --> 00:21:23,920 THERE IS THIS GROUP OF AREAS 518 00:21:23,920 --> 00:21:25,320 THAT ROUTINELY WENT DOWN ANY 519 00:21:25,320 --> 00:21:26,640 TIME WE DID ANY KIND OF AN 520 00:21:26,640 --> 00:21:27,200 EXPERIMENT LIKE THIS. 521 00:21:27,200 --> 00:21:30,560 SO THIS APPEARED IN SEVERAL 522 00:21:30,560 --> 00:21:32,200 PAPERS, SO IF YOU WANT TO CLICK 523 00:21:32,200 --> 00:21:35,400 BELOW THERE. 524 00:21:35,400 --> 00:21:37,240 THE FIRST WAS A COMPREHENSIVE 525 00:21:37,240 --> 00:21:39,400 LOOK ACROSS ALL SORTS OF 526 00:21:39,400 --> 00:21:40,960 DIFFERENT EXPERIMENTS THAT 527 00:21:40,960 --> 00:21:42,840 GORDON SHULMAN PUT TOGETHER FOR 528 00:21:42,840 --> 00:21:47,080 US, AND THE PROBLEM WAS, WHAT 529 00:21:47,080 --> 00:21:48,400 DOES THIS TELL US ABOUT THE 530 00:21:48,400 --> 00:21:48,880 BRAIN FUNCTION? 531 00:21:48,880 --> 00:21:52,320 AND OF COURSE THE SCEP TIPS SKED 532 00:21:52,320 --> 00:21:54,120 HAVE SAID WHEN YOU'RE JUST IN A 533 00:21:54,120 --> 00:21:55,560 CONTROL STATE LOOKING AT A BLANK 534 00:21:55,560 --> 00:21:59,680 SCREEN EU OBVIOUSLY NOT 535 00:21:59,680 --> 00:22:00,960 THINKING, ARE YOU DAYDREAMING 536 00:22:00,960 --> 00:22:02,960 ABOUT WHAT HAPPENED OR 537 00:22:02,960 --> 00:22:03,920 DAYDREAMING ABOUT WHAT YOU DID 538 00:22:03,920 --> 00:22:07,560 YET OR WHAT YOU'LL DO TOMORROW? 539 00:22:07,560 --> 00:22:11,000 SO THIS ISSUE WAS, WHAT IS THE 540 00:22:11,000 --> 00:22:12,560 BASELINE LEVEL OF ACTIVITY IN 541 00:22:12,560 --> 00:22:14,520 THE BRAIN? 542 00:22:14,520 --> 00:22:18,360 AND WE RESORTED IN THIS 543 00:22:18,360 --> 00:22:21,000 ENTERPRISE TO WHAT HAD BEEN 544 00:22:21,000 --> 00:22:22,720 OBSERVED FROM METABOLIC STUDIES 545 00:22:22,720 --> 00:22:24,840 OF THE BRAIN THAT THERE IS A 546 00:22:24,840 --> 00:22:27,000 MARKED RELATIONSHIP IN THE 547 00:22:27,000 --> 00:22:29,400 RESTING BRAIN BETWEEN BLOOD FLOW 548 00:22:29,400 --> 00:22:30,920 AND OXYGEN CONSUMPTION. 549 00:22:30,920 --> 00:22:35,760 SO USING THAT AS THE BASIS FOR A 550 00:22:35,760 --> 00:22:37,160 BASELINE, WE LOOK AT THE BRAIN 551 00:22:37,160 --> 00:22:40,680 AGAIN AND WE WERE ABLE TO 552 00:22:40,680 --> 00:22:41,760 DETERMINE THAT THERE WAS NOTHING 553 00:22:41,760 --> 00:22:46,800 GOING ON IN THE BASELINE THAT 554 00:22:46,800 --> 00:22:48,880 STOOD OUT FROM HIS BACKGROUND. 555 00:22:48,880 --> 00:22:50,960 SO WE CAME ABOUT WITH THE NOTION 556 00:22:50,960 --> 00:22:55,880 THAT THIS ORGANIZATION, WHICH 557 00:22:55,880 --> 00:22:57,880 BECAME THE FOUNDATION OF WORK 558 00:22:57,880 --> 00:22:59,120 GOING FORWARD, WAS ACTUALLY SOME 559 00:22:59,120 --> 00:23:04,080 SORT OF A DEFAULT MODE LARGE 560 00:23:04,080 --> 00:23:05,720 SCALE ORGANIZATION OF THE HUMAN 561 00:23:05,720 --> 00:23:08,720 BRAIN, PROBABLY ANY MAMMALIAN 562 00:23:08,720 --> 00:23:09,000 BRAIN. 563 00:23:09,000 --> 00:23:13,600 SO IF I CAN HAVE THE NEXT SLIDE, 564 00:23:13,600 --> 00:23:15,440 SO THE QUESTION WAS, HOW DO WE 565 00:23:15,440 --> 00:23:16,360 GO FROM HERE? 566 00:23:16,360 --> 00:23:18,200 WHAT DO WE DO ABOUT THIS? 567 00:23:18,200 --> 00:23:21,440 AND THE ANSWER WAS, WELL, ENTER 568 00:23:21,440 --> 00:23:24,080 ANOTHER TECHNOLOGY, AND THAT IS 569 00:23:24,080 --> 00:23:27,160 FUNCTIONAL MAGNETIC RESONANCE 570 00:23:27,160 --> 00:23:28,920 IMAGING, WHICH ITSELF HAS A VERY 571 00:23:28,920 --> 00:23:32,080 INTERESTING HISTORY. 572 00:23:32,080 --> 00:23:32,960 SO I'M GOING TO HAVE THE NEXT 573 00:23:32,960 --> 00:23:35,720 SLIDE. 574 00:23:35,720 --> 00:23:36,800 THE KEY THING TO UNDERSTAND WHEN 575 00:23:36,800 --> 00:23:37,920 YOU LOOK AT WHAT I'M GOING TO 576 00:23:37,920 --> 00:23:40,080 TELL YOU IS WHAT HAPPENS WHEN 577 00:23:40,080 --> 00:23:41,920 THE BRAIN CHANGES ITS 578 00:23:41,920 --> 00:23:44,680 METABOLISM? 579 00:23:44,680 --> 00:23:46,160 IN THE COURSE OF DOING A TASK. 580 00:23:46,160 --> 00:23:47,520 SO LET'S JUST SUPPOSE YOU'RE IN 581 00:23:47,520 --> 00:23:50,160 A SCANNER AND YOU LOOK AT A 582 00:23:50,160 --> 00:23:51,640 BLANK SCREEN AND THEN WE PUT UP 583 00:23:51,640 --> 00:23:55,200 A REVERSING ANNULAR 584 00:23:55,200 --> 00:23:55,720 CHECKERBOARD. 585 00:23:55,720 --> 00:23:57,320 THE COMMON WISDOM WAS THE BLOOD 586 00:23:57,320 --> 00:23:58,760 FLOW WOULD GO UP, OXYGEN 587 00:23:58,760 --> 00:24:01,520 CONSUMPTION WOULD GO UP, GLUCOSE 588 00:24:01,520 --> 00:24:03,800 CONSUMPTION WOULD GO UP. 589 00:24:03,800 --> 00:24:06,440 THAT WAS THE DOGMA. 590 00:24:06,440 --> 00:24:08,160 AND THERE WAS A SMALL AMOUNT OF 591 00:24:08,160 --> 00:24:10,280 EVIDENCE TO SUPPORT THAT WHICH 592 00:24:10,280 --> 00:24:12,240 BOTHERED ME. 593 00:24:12,240 --> 00:24:15,160 MY REACTION TO THIS WAS, WE 594 00:24:15,160 --> 00:24:16,560 BETTER BE DAMN SURE THAT THIS IS 595 00:24:16,560 --> 00:24:17,680 WHAT'S GOING ON HERE. 596 00:24:17,680 --> 00:24:19,440 AND WE WERE DEEPLY SURPRISED AS 597 00:24:19,440 --> 00:24:21,280 WAS THE WORLD WHEN THIS CAME 598 00:24:21,280 --> 00:24:21,840 OUT. 599 00:24:21,840 --> 00:24:23,600 THE BLOOD FLOW WENT UP, THE 600 00:24:23,600 --> 00:24:25,400 GLUCOSE CONSUMPTION WENT UP, BUT 601 00:24:25,400 --> 00:24:29,880 THE OXYGEN UTILIZATION DIDN'T 602 00:24:29,880 --> 00:24:30,560 MATCH THAT CHANGE. 603 00:24:30,560 --> 00:24:31,840 SO WHAT HAPPENED HERE WAS THAT 604 00:24:31,840 --> 00:24:33,400 THE OXYGEN AVAILABILITY TO THE 605 00:24:33,400 --> 00:24:36,680 BRAIN HAD INCREASED. 606 00:24:36,680 --> 00:24:37,680 AND THAT THE ENERGY THAT WAS 607 00:24:37,680 --> 00:24:39,720 REQUIRED FOR THIS PARTICULAR 608 00:24:39,720 --> 00:24:42,040 BRIEF CHANGE WAS BEING PROVIDED 609 00:24:42,040 --> 00:24:43,360 SOLELY BY GLUCOSE OR WHAT WE'VE 610 00:24:43,360 --> 00:24:47,160 COME TO CALL AEROBIC GLYCOLYSIS. 611 00:24:47,160 --> 00:24:51,320 NOW THIS IS IMPORTANT FROM THE 612 00:24:51,320 --> 00:24:54,400 PERSPECTIVE OF FMRI OR MRI. 613 00:24:54,400 --> 00:24:59,400 SO HIT THE BUTTON. 614 00:24:59,400 --> 00:25:02,920 THE ISSUE THAT IS IMPORTANT TO 615 00:25:02,920 --> 00:25:05,320 UNDERSTAND HERE IS THAT THE MR 616 00:25:05,320 --> 00:25:09,800 SIGNALING SYSTEM IS VERY 617 00:25:09,800 --> 00:25:12,320 SENSITIVE TO THE OXYGENATION OF 618 00:25:12,320 --> 00:25:15,880 HEMOGLOBIN, AND MICHAEL FARADAY 619 00:25:15,880 --> 00:25:16,920 FIRST ADDRESSED THIS AS YOU MAY 620 00:25:16,920 --> 00:25:20,120 KNOW, HE WAS INTERESTED IN 621 00:25:20,120 --> 00:25:20,760 ELECTROMAGNETISM AND SO FORTH, 622 00:25:20,760 --> 00:25:23,160 HE LOOKED AT BLOOD AND DIDN'T 623 00:25:23,160 --> 00:25:24,480 SEE ANY DIFFERENCE IN THE 624 00:25:24,480 --> 00:25:26,560 MAGNETIC FIELD, BUT HE'D USED 625 00:25:26,560 --> 00:25:29,520 DRIED BLOOD AND IN HIS 626 00:25:29,520 --> 00:25:30,800 LABORATORY JOURNAL, HE SAID 627 00:25:30,800 --> 00:25:35,000 SHOULD TRY LIQUID BLOOD. 628 00:25:35,000 --> 00:25:40,520 AND IT WAS LINUS PAULING IN 1937 629 00:25:40,520 --> 00:25:42,280 THAT DID PICK UP ON THIS AND DID 630 00:25:42,280 --> 00:25:46,480 FIND OUT THAT DEOXYGENATED 631 00:25:46,480 --> 00:25:48,320 HEMOGLOBIN IS PARAMAGNETIC. 632 00:25:48,320 --> 00:25:51,480 SO IT INTERFERES WITH THE 633 00:25:51,480 --> 00:25:56,520 MAGNETIC FIELD, SO YOU SEE THE 634 00:25:56,520 --> 00:25:59,360 OXYGEN REMOVED HERE, YOU CAN SEE 635 00:25:59,360 --> 00:26:01,200 THESE LITTLE FLUFFY LITTLE LINES 636 00:26:01,200 --> 00:26:02,320 IN THE BACK. 637 00:26:02,320 --> 00:26:03,400 THAT'S DISRUPTION OF THE 638 00:26:03,400 --> 00:26:05,200 MAGNETIC FIELD. 639 00:26:05,200 --> 00:26:11,400 AND IT WAS SEIJI OGAWA AT THE 640 00:26:11,400 --> 00:26:12,240 BELL LABORATORY THAT SAID WHAT 641 00:26:12,240 --> 00:26:16,040 IF I PUT THIS LITTLE RODENT ON 642 00:26:16,040 --> 00:26:16,520 OXYGEN, WHAT HAPPENS. 643 00:26:16,520 --> 00:26:19,160 HERE YOU CAN SEE THE VEINS WHICH 644 00:26:19,160 --> 00:26:20,560 CONTAIN DEOXYGENATED HEMOGLOBIN. 645 00:26:20,560 --> 00:26:22,120 HERE THE OXYGENATION HAS BEEN 646 00:26:22,120 --> 00:26:24,640 REPLACED AND, BINGO, WE HAVE A 647 00:26:24,640 --> 00:26:27,040 MEASURE OF THESE METABOLIC 648 00:26:27,040 --> 00:26:28,480 CHANGES IN TERMS OF OXYGEN 649 00:26:28,480 --> 00:26:30,120 AVAILABILITY. 650 00:26:30,120 --> 00:26:31,760 SO YOU WANT TO HIT THE BUTTON 651 00:26:31,760 --> 00:26:37,560 AGAIN? 652 00:26:37,560 --> 00:26:43,120 OUTCOMES FMRI BOLD SIGNAL WHICH 653 00:26:43,120 --> 00:26:44,840 REALLY REVOLUTIONIZED HOW WE GET 654 00:26:44,840 --> 00:26:46,640 ACCESS TO THIS BUT IT'S 655 00:26:46,640 --> 00:26:47,480 IMPORTANT TO REMEMBER HOW THAT 656 00:26:47,480 --> 00:26:48,040 SIGNAL WORKS. 657 00:26:48,040 --> 00:26:49,680 SO I HOPE YOU KIND OF GRASP THE 658 00:26:49,680 --> 00:26:54,360 SENSE OF IT. 659 00:26:54,360 --> 00:26:56,000 NOW, AN INTERESTING FEATURE OF 660 00:26:56,000 --> 00:26:59,160 THIS SIGNAL IS THAT IT'S NOISY. 661 00:26:59,160 --> 00:27:01,600 IF YOU LOOK AT AN MR SIGNAL AS 662 00:27:01,600 --> 00:27:04,760 IT'S TRACED OUT AND YOU SQUINT 663 00:27:04,760 --> 00:27:06,520 HARD, YOU'LL SEE THERE'S SOME 664 00:27:06,520 --> 00:27:09,680 LITTLE WIGGLES IN IT, SO WE JUST 665 00:27:09,680 --> 00:27:10,880 INCREASED THE SCALE HERE SO YOU 666 00:27:10,880 --> 00:27:12,200 CAN ACTUALLY SEE WHAT IT LOOKS 667 00:27:12,200 --> 00:27:12,760 LIKE. 668 00:27:12,760 --> 00:27:14,640 IT JUST LOOKS LIKE NOISE. 669 00:27:14,640 --> 00:27:17,040 SO THE QUESTION WAS, CAN IT TELL 670 00:27:17,040 --> 00:27:18,760 US ANYTHING ABOUT THE BRAIN'S 671 00:27:18,760 --> 00:27:21,920 BRAIN'SSPONTANEOUS ACTIVITY, ANE 672 00:27:21,920 --> 00:27:26,960 ANSWER IS A RESOUNDING YES. 673 00:27:26,960 --> 00:27:30,360 THIS WAS A GRADUATE STUDENT AT 674 00:27:30,360 --> 00:27:31,120 THE MEDICAL COLLEGE OF WISCONSIN 675 00:27:31,120 --> 00:27:33,120 WORKING UNDER THE GUIDANCE OF 676 00:27:33,120 --> 00:27:35,280 JAMES HYDE, AND HE'D BEEN ASKED 677 00:27:35,280 --> 00:27:37,000 THIS QUESTION, HOW DO WE THINK 678 00:27:37,000 --> 00:27:39,880 ABOUT THE NOISE IN THIS SIGNAL, 679 00:27:39,880 --> 00:27:41,600 AND HIS APPROACH TO THIS PROBLEM 680 00:27:41,600 --> 00:27:44,160 WAS TO LOOK AT THE MOTOR SYSTEM 681 00:27:44,160 --> 00:27:48,400 IN THE BRAIN, AND ON THE LEFT, 682 00:27:48,400 --> 00:27:54,520 YOU CAN SEE THAT IF YOU 683 00:27:54,520 --> 00:27:55,280 STIMULATE ON THE RIGHT-HAND 684 00:27:55,280 --> 00:27:56,600 SIDE, WHICH YOU WILL GET A 685 00:27:56,600 --> 00:28:00,240 SIGNAL AT B, IN THE BRAIN, YOU 686 00:28:00,240 --> 00:28:05,680 GET A MAP OF MOTOR AREA THAT WAS 687 00:28:05,680 --> 00:28:06,760 RESPONSIBLE FOR MOVING THE HAND. 688 00:28:06,760 --> 00:28:08,640 AND YOU CAN DO IT ON BOTH SIDES 689 00:28:08,640 --> 00:28:13,280 AND SO YOU GET AN A AND A B AND 690 00:28:13,280 --> 00:28:14,800 A C IN THE SUPPLEMENTARY MOTOR 691 00:28:14,800 --> 00:28:15,440 AREA. 692 00:28:15,440 --> 00:28:19,240 NOW, IF YOU GO IN AND PUT YOUR 693 00:28:19,240 --> 00:28:25,400 DETECTOR ON B OR A OR C, AND YOU 694 00:28:25,400 --> 00:28:26,840 SAY WHAT IS IT CORRELATED WITH, 695 00:28:26,840 --> 00:28:30,680 IT'S THIS WHOLE COMPLEX. 696 00:28:30,680 --> 00:28:32,640 THEY'RE ALL COORDINATED, THEY'RE 697 00:28:32,640 --> 00:28:35,680 ALL MOVING TOGETHER. 698 00:28:35,680 --> 00:28:40,080 THIS WAS A REMARKABLE 699 00:28:40,080 --> 00:28:40,920 OBSERVATION, OF WHICH THERE WERE 700 00:28:40,920 --> 00:28:44,200 EVIDENCE OF IT LIKELY TO BE THIS 701 00:28:44,200 --> 00:28:47,480 WAY, BUT NOBODY HAD PAID ANY 702 00:28:47,480 --> 00:28:50,880 ATTENTION TO IT UNTIL BHARAT 703 00:28:50,880 --> 00:28:59,280 BISWAL GAVE THIS. 704 00:28:59,280 --> 00:29:01,160 SO OUR INTEREST, ACTUALLY I KNEW 705 00:29:01,160 --> 00:29:04,680 ABOUT THIS, BUT THERE WAS SOME 706 00:29:04,680 --> 00:29:06,680 SKEPTICISM ABOUT THIS WHEN 707 00:29:06,680 --> 00:29:11,760 ANOTHER FRIEND OF MINE, MIKE 708 00:29:11,760 --> 00:29:14,160 GRECIUS AT STANFORD AND HIS 709 00:29:14,160 --> 00:29:16,560 COLLEAGUES DECIDED TO LOOK AT 710 00:29:16,560 --> 00:29:18,240 THIS DEFAULT NETWORK WE TALKED 711 00:29:18,240 --> 00:29:20,760 EARLIER ABOUT AND PUBLISHED ON. 712 00:29:20,760 --> 00:29:22,800 THEY LOOKED AT PLACING A REGION 713 00:29:22,800 --> 00:29:24,160 OF INTEREST EITHER IN THE BACK 714 00:29:24,160 --> 00:29:25,400 OR THE FRONT, WHERE THOSE TWO 715 00:29:25,400 --> 00:29:27,520 THINGS ARE, AND BLOODY WELL, 716 00:29:27,520 --> 00:29:28,640 THEY'RE COORDINATED JUST EXACTLY 717 00:29:28,640 --> 00:29:33,800 THE SAME WAY AS THE MOTOR 718 00:29:33,800 --> 00:29:34,320 SYSTEM. 719 00:29:34,320 --> 00:29:35,840 SO THIS KIND OF LAUNCHED THIS 720 00:29:35,840 --> 00:29:37,920 WHOLE IDEA OF RESTING STATE 721 00:29:37,920 --> 00:29:38,800 FUNCTIONAL CONNECTIVITY IN THE 722 00:29:38,800 --> 00:29:40,200 BRAIN. 723 00:29:40,200 --> 00:29:43,400 AND I THINK A THE BOTTOM OF THE 724 00:29:43,400 --> 00:29:44,360 SCREEN DOESN'T SHOW THE FIGURE, 725 00:29:44,360 --> 00:29:47,120 BUT JUST FOR THE AMUSEMENT SAKE, 726 00:29:47,120 --> 00:29:52,400 I LOOKED AT THE PUBMED AND THE 727 00:29:52,400 --> 00:29:55,360 NATIONATIONAL LIBRARY OF MEDICI, 728 00:29:55,360 --> 00:29:56,400 HOW MANY PAPERS ARE THERE ON 729 00:29:56,400 --> 00:29:58,120 THIS SUBJECT PRESENTLY, AND IT'S 730 00:29:58,120 --> 00:29:59,880 CLOSE TO 250,000 PAPERS, IF YOU 731 00:29:59,880 --> 00:30:02,320 PUT IN AS YOUR SEARCH ITEMS 732 00:30:02,320 --> 00:30:05,600 "BRAIN" AND "FUNCTIONAL MAGNETIC 733 00:30:05,600 --> 00:30:06,680 RESONANCE IMAGING." 734 00:30:06,680 --> 00:30:08,520 IT'S A WORLD ALL OF ITS OWN, 735 00:30:08,520 --> 00:30:09,760 DOING ALL KINDS OF THINGS, SOME 736 00:30:09,760 --> 00:30:14,600 BETTER THAN OTHERS. 737 00:30:14,600 --> 00:30:17,840 SO THIS JUST IS ANOTHER GRAPHIC 738 00:30:17,840 --> 00:30:19,080 ILLUSTRATION OF WHAT THIS KIND 739 00:30:19,080 --> 00:30:21,320 OF LOOKS LIKE IN OPERATIONAL 740 00:30:21,320 --> 00:30:21,560 TERMS. 741 00:30:21,560 --> 00:30:26,680 YOU PUT A REGION OF INTEREST IN 742 00:30:26,680 --> 00:30:27,800 SOME PLACE IN SOMEBODY'S BRAIN 743 00:30:27,800 --> 00:30:29,200 AND YOU FOLLOW THIS THROUGH MANY 744 00:30:29,200 --> 00:30:31,280 ITERATIONS AND YOU GET THIS 745 00:30:31,280 --> 00:30:31,880 SIGNAL. 746 00:30:31,880 --> 00:30:35,040 AND IF YOU HIT THE BUTTON AGAIN, 747 00:30:35,040 --> 00:30:38,840 YOU CAN EASILY REPRODUCE 748 00:30:38,840 --> 00:30:39,720 BHARAT'S OBSERVATION AND 749 00:30:39,720 --> 00:30:40,720 FURTHERMORE, YOU CAN GET THE 750 00:30:40,720 --> 00:30:45,200 FOLLOWING. 751 00:30:45,200 --> 00:30:49,240 YOU GET A WHOLE ARRANGEMENT OF 752 00:30:49,240 --> 00:30:50,440 AREAS THAT FORM NETWORKS WITHIN 753 00:30:50,440 --> 00:30:53,400 THE BRAIN, AND THE ACCOUNT 754 00:30:53,400 --> 00:30:54,480 VARIES SOMEWHAT DEPENDING ON 755 00:30:54,480 --> 00:30:55,920 WHO'S DOING THE STUDY AND 756 00:30:55,920 --> 00:30:56,920 WHATEVER, BUT THERE'S SOMETHING 757 00:30:56,920 --> 00:31:00,520 LIKE 15 TO 20 OF THESE EASILY 758 00:31:00,520 --> 00:31:01,400 REPRODUCIBLE RELATIONSHIPS 759 00:31:01,400 --> 00:31:03,000 WITHIN THE BRAIN. 760 00:31:03,000 --> 00:31:08,480 THAT EXIST ON A FUNCTIONAL 761 00:31:08,480 --> 00:31:12,840 BASIS, AND EASILY DETECTED WITH 762 00:31:12,840 --> 00:31:14,160 FMRI. 763 00:31:14,160 --> 00:31:17,680 SO THE QUESTION, OF COURSE, IS 764 00:31:17,680 --> 00:31:18,680 NEUROPHYSIOLOGICALLY WHAT DOES 765 00:31:18,680 --> 00:31:22,520 THIS RESTING STATE FMRI SIGNAL 766 00:31:22,520 --> 00:31:23,040 REPRESENT? 767 00:31:23,040 --> 00:31:25,760 AND THE ANSWER IS SOMETHING 768 00:31:25,760 --> 00:31:26,760 CALLED INFRA-SLOW ACTIVITY. 769 00:31:26,760 --> 00:31:29,040 THAT IS LESS THAN 1 HERTZ. 770 00:31:29,040 --> 00:31:31,120 IT'S USUALLY AROUND .1 HERTZ. 771 00:31:31,120 --> 00:31:34,640 IF I CAN HAVE THE NEXT SLIDE. 772 00:31:34,640 --> 00:31:36,480 VARIOUS PEOPLE HAVE LOOKED AT 773 00:31:36,480 --> 00:31:37,360 THIS. 774 00:31:37,360 --> 00:31:39,200 THIS IS WORK OUT OF WASHINGTON 775 00:31:39,200 --> 00:31:39,960 UNIVERSITY. 776 00:31:39,960 --> 00:31:41,840 I'M RATHER PROUD OF THIS ONE, 777 00:31:41,840 --> 00:31:44,280 PARTICULARLY BECAUSE IT INVOLVES 778 00:31:44,280 --> 00:31:48,880 SIX DIFFERENT LABORATORIES. 779 00:31:48,880 --> 00:31:51,040 THE RED AUTHORS UP THERE ARE ALL 780 00:31:51,040 --> 00:31:52,480 GRADUATE STUDENTS WHO WORKED ON 781 00:31:52,480 --> 00:31:53,080 THIS PROJECT. 782 00:31:53,080 --> 00:31:56,760 IT WAS ORGANIZED BY ANDREW KRAFT 783 00:31:56,760 --> 00:32:01,960 IN ONE OF THE LABS AND ANISH 784 00:32:01,960 --> 00:32:03,200 MITRA, ONE OF MY STUDENTS THAT'S 785 00:32:03,200 --> 00:32:04,160 NOW AT STANFORD. 786 00:32:04,160 --> 00:32:06,240 WHAT IT IS IS AN INCREDIBLY 787 00:32:06,240 --> 00:32:09,600 COLLABORATIVE LOOK AT A MOUSE 788 00:32:09,600 --> 00:32:11,480 USING CALCIUM HEMOGLOBIN 789 00:32:11,480 --> 00:32:12,680 IMAGING, THE CALCIUM FOR THE 790 00:32:12,680 --> 00:32:14,040 ACTIVITY AND THE HEMOGLOBIN TO 791 00:32:14,040 --> 00:32:19,680 GET IT BACK TOWARDS THE BOLD 792 00:32:19,680 --> 00:32:21,440 SIGNAL ITSELF, AND WE ACTUALLY 793 00:32:21,440 --> 00:32:23,280 USED LAMINAR ELECTROPHYSIOLOGY 794 00:32:23,280 --> 00:32:25,840 AS WELL. 795 00:32:25,840 --> 00:32:29,120 IT WAS JUST VERY HEARTENING TO 796 00:32:29,120 --> 00:32:30,720 SEE HOW YOU CAN GET A VERY 797 00:32:30,720 --> 00:32:32,720 DIVERSE GROUP OF PEOPLE TOGETHER 798 00:32:32,720 --> 00:32:34,800 TO GET SOME ANSWERS AS TO WHAT'S 799 00:32:34,800 --> 00:32:35,960 GOING ON. 800 00:32:35,960 --> 00:32:38,800 AND WE CONCLUDED FROM THIS THAT 801 00:32:38,800 --> 00:32:43,120 THE FMRI WAS A SPECIFIC MARKER 802 00:32:43,120 --> 00:32:44,640 OF THIS INFRA-SLOW ACTIVITY AND 803 00:32:44,640 --> 00:32:46,000 IT TRAVELS THROUGH THE CORTEX IN 804 00:32:46,000 --> 00:32:49,440 A VERY SPECIFIC WAY, AND IT IS 805 00:32:49,440 --> 00:32:49,880 STATES-SPECIFIC. 806 00:32:49,880 --> 00:32:53,400 SO IF YOU LOOK UP ON THE A UP 807 00:32:53,400 --> 00:32:56,000 THERE ON THE SCREEN, YOU CAN 808 00:32:56,000 --> 00:32:59,400 LOOK AT IT IN TWO DIFFERENT 809 00:32:59,400 --> 00:33:00,160 ANESTHETICS HERE, AND YOU'RE 810 00:33:00,160 --> 00:33:03,240 LOOKING AT DELTA ACTIVITY AND 811 00:33:03,240 --> 00:33:04,520 INFRA-SLOW ACTIVITY, AND YOU CAN 812 00:33:04,520 --> 00:33:06,720 SEE THEY'RE RECIPROCALLY MOVING 813 00:33:06,720 --> 00:33:08,480 IN OPPOSITE DIRECTIONS, AND AS 814 00:33:08,480 --> 00:33:11,760 YOU GO FROM THE ANESTHETIZED 815 00:33:11,760 --> 00:33:13,080 STATE TO THE OTHER, THOSE 816 00:33:13,080 --> 00:33:13,960 SIGNALS TRAVEL IN THE OPPOSITE 817 00:33:13,960 --> 00:33:16,000 DIRECTION. 818 00:33:16,000 --> 00:33:19,200 THIS IS PROVEN TO BE VERY, VERY 819 00:33:19,200 --> 00:33:21,160 USEFUL AS YOU BEGIN TO THINK OF 820 00:33:21,160 --> 00:33:23,360 HOW THE BRAIN TALKS TO ITSELF, 821 00:33:23,360 --> 00:33:25,000 HOW ARE THE CONVERSATIONS 822 00:33:25,000 --> 00:33:34,200 ACTUALLY GOING ON IN HERE. 823 00:33:34,200 --> 00:33:35,520 THIS GENERAL IDEA HAS ACTUALLY 824 00:33:35,520 --> 00:33:36,600 BEEN AROUND FOR A WHILE. 825 00:33:36,600 --> 00:33:38,360 WHEN I GO TO READ A PAPER THAT 826 00:33:38,360 --> 00:33:40,400 SOMEBODY IS TALKING ABOUT THIS 827 00:33:40,400 --> 00:33:42,080 SORT OF THING, I ALWAYS LOOK FOR 828 00:33:42,080 --> 00:33:47,120 THIS ONE TOP REFERENCE HERE FROM 829 00:33:47,120 --> 00:33:51,160 NINA ALADJALOVA, A RUSSIAN 830 00:33:51,160 --> 00:33:52,360 NEUROPHYSIOLOGIST WHO PUBLISHED 831 00:33:52,360 --> 00:33:55,000 A LETTER TO NATURE IN WHICH SHE 832 00:33:55,000 --> 00:33:57,040 COINED THE TERM INFRA-SLOW 833 00:33:57,040 --> 00:33:57,920 RHYTHMIC OSCILLATIONS. 834 00:33:57,920 --> 00:33:58,920 SHE SUBSEQUENTLY WROTE A BOOK 835 00:33:58,920 --> 00:34:00,240 ABOUT THIS, AND IF YOU'RE AT ALL 836 00:34:00,240 --> 00:34:02,000 INTERESTED IN IT, I VERY MUCH 837 00:34:02,000 --> 00:34:04,080 URGE YOU TO HAVE A LOOK AT THIS. 838 00:34:04,080 --> 00:34:06,320 AND IF YOU WANT TO SEE IT IN A 839 00:34:06,320 --> 00:34:10,920 MORE DETAILED WAY, THESE TWO 840 00:34:10,920 --> 00:34:12,120 PAPERS, ONE IN THE JOURNAL OF 841 00:34:12,120 --> 00:34:14,560 NEUROSCIENCE AND THE OTHER IN 842 00:34:14,560 --> 00:34:17,080 NEUROIMAGING BY THESE GROUPS IN 843 00:34:17,080 --> 00:34:18,480 SCANDINAVIA IN WHICH THEY HAVE 844 00:34:18,480 --> 00:34:20,160 LOOKED AT BOTH THE BEHAVIOR THAT 845 00:34:20,160 --> 00:34:21,680 GOES WITH THIS AND THESE 846 00:34:21,680 --> 00:34:25,160 DIFFERENT FREQUENCIES THAT ARE 847 00:34:25,160 --> 00:34:26,480 PART OF THE SPECTRUM OF 848 00:34:26,480 --> 00:34:27,680 ACTIVITIES WITHIN THE BRAIN. 849 00:34:27,680 --> 00:34:30,200 AND PARTICULARLY THE ROLE OF THE 850 00:34:30,200 --> 00:34:31,280 INFRA-SLOW ACTIVITY, WHICH IS 851 00:34:31,280 --> 00:34:34,360 PICKED UP IN THIS GREY SYMBOL 852 00:34:34,360 --> 00:34:36,760 HERE AND BEHAVIOR, WHICH VARIES 853 00:34:36,760 --> 00:34:38,480 ACCORDINGLY TO THIS, IS ALSO 854 00:34:38,480 --> 00:34:41,040 DEPICTED. 855 00:34:41,040 --> 00:34:42,760 I'M NOT GOING TO GET INTO THE 856 00:34:42,760 --> 00:34:45,080 REAL GRITTY DETAILS OF THIS, BUT 857 00:34:45,080 --> 00:34:46,360 I URGE YOU IF YOU FIND THIS 858 00:34:46,360 --> 00:34:47,680 INTERESTING TO LOOK AT THESE TWO 859 00:34:47,680 --> 00:34:48,840 PAPERS IN PARTICULAR AND OF 860 00:34:48,840 --> 00:34:50,880 COURSE READ NINA'S PIECE IN 861 00:34:50,880 --> 00:34:51,320 NATURE. 862 00:34:51,320 --> 00:34:54,280 IT'S A REMINDER THAT THERE ARE 863 00:34:54,280 --> 00:34:55,680 THESE GEMS OUT THERE THAT NEED 864 00:34:55,680 --> 00:35:02,160 TO BE RECOGNIZED. 865 00:35:02,160 --> 00:35:03,920 SO HOW DO THESE OBSERVATIONS 866 00:35:03,920 --> 00:35:05,760 INFORM A FUNCTIONALLY INTEGRATED 867 00:35:05,760 --> 00:35:06,200 VIEW OF THE BRAIN? 868 00:35:06,200 --> 00:35:08,680 WHAT I WOULD LIKE TO URGE YOU IS 869 00:35:08,680 --> 00:35:12,320 TO THINK ABOUT TIME. 870 00:35:12,320 --> 00:35:13,280 BECAUSE WE'RE SO MUCH INTERESTED 871 00:35:13,280 --> 00:35:14,480 IN WHERE THINGS ARE HAPPENING 872 00:35:14,480 --> 00:35:16,480 AND WHAT THE RELATIONSHIP IS, 873 00:35:16,480 --> 00:35:18,240 BUT WHAT IS THE ROLE OF TIME AND 874 00:35:18,240 --> 00:35:21,560 HOW SHOULD WE BE THINKING ABOUT 875 00:35:21,560 --> 00:35:22,960 THIS? 876 00:35:22,960 --> 00:35:25,240 AND I'M GOING TO TOUCH ON SOME 877 00:35:25,240 --> 00:35:27,800 WORK, AGAIN, BY ONE OF MY 878 00:35:27,800 --> 00:35:31,680 FORMER -- MY LAST GRADUATE 879 00:35:31,680 --> 00:35:33,360 STUDENT. 880 00:35:33,360 --> 00:35:36,200 IN '86, I DECIDED NOT TO TAKE 881 00:35:36,200 --> 00:35:39,360 ANY MORE, BUT HE IS VERY 882 00:35:39,360 --> 00:35:40,760 TALENTED, RYAN RAUT, ALONG WITH 883 00:35:40,760 --> 00:35:44,280 THE REST OF THE TEAM. 884 00:35:44,280 --> 00:35:45,360 SO THE ISSUE OF TIME IS 885 00:35:45,360 --> 00:35:47,880 SOMETHING THAT CAME LARGELY BY 886 00:35:47,880 --> 00:35:51,360 THE WORK OF MY OTHER GRADUATE -- 887 00:35:51,360 --> 00:35:55,760 RECENT GRADUATE STUDENT, ANISH 888 00:35:55,760 --> 00:35:58,800 MITRA, WHO IS AT STANFORD, HE 889 00:35:58,800 --> 00:36:03,840 WAS AN UNDERGRADUATE MATHEMATICS 890 00:36:03,840 --> 00:36:05,000 MAJOR AND THEN WENT TO 891 00:36:05,000 --> 00:36:05,600 WASHINGTON UNIVERSITY. 892 00:36:05,600 --> 00:36:07,160 THE IDEA IS IF YOU'RE LOOKING AT 893 00:36:07,160 --> 00:36:11,720 THESE RELATIONSHIPS, SAY THE 894 00:36:11,720 --> 00:36:13,960 DEFAULT NODE NETWORK, THERE IS 895 00:36:13,960 --> 00:36:15,160 THIS CORRELATED RELATIONSHIP 896 00:36:15,160 --> 00:36:16,360 BETWEEN THE COMPONENTS OF THIS 897 00:36:16,360 --> 00:36:18,480 SYSTEM, BUT YOU CAN ACTUALLY 898 00:36:18,480 --> 00:36:19,880 LOOK AT THE TIME DIFFERENCES 899 00:36:19,880 --> 00:36:21,720 BETWEEN TWO POSITIONS. 900 00:36:21,720 --> 00:36:24,120 THERE IS THIS ACTIVITY IS NOT 901 00:36:24,120 --> 00:36:27,000 ONLY SYNCHRONOUS BETWEEN AREAS, 902 00:36:27,000 --> 00:36:28,960 BUT THERE IS A TIME DIFFERENCE 903 00:36:28,960 --> 00:36:34,280 THAT'S HIGHLY REPRODUCIBLE. 904 00:36:34,280 --> 00:36:35,480 SO THE ISSUE AS WE WERE TALKING 905 00:36:35,480 --> 00:36:40,200 ABOUT IS OF PROPAGATING SIGNAL. 906 00:36:40,200 --> 00:36:42,400 SO THERE'S VARIOUS WAYS TO 907 00:36:42,400 --> 00:36:43,480 DEPICT THIS. 908 00:36:43,480 --> 00:36:47,880 HERE'S THE USUAL SORT OF MAPPING 909 00:36:47,880 --> 00:36:49,280 OF NETWORKS IN THE BRAIN, AND 910 00:36:49,280 --> 00:36:52,480 HERE IS THE -- THE TIME 911 00:36:52,480 --> 00:36:54,400 DIFFERENCE IS -- WHEN YOU LOOK 912 00:36:54,400 --> 00:36:56,080 AT IT AND INCLUDE WHO'S EARLY 913 00:36:56,080 --> 00:36:57,720 AND WHO'S LATE IN THESE 914 00:36:57,720 --> 00:36:59,440 RELATIONSHIPS. 915 00:36:59,440 --> 00:37:01,320 BUT OBVIOUSLY WE NEEDED MORE 916 00:37:01,320 --> 00:37:09,400 DETAILS HERE TO THINK ABOUT 917 00:37:09,400 --> 00:37:09,720 THIS. 918 00:37:09,720 --> 00:37:11,040 THIS WAS ONE WHERE I HAD TO 919 00:37:11,040 --> 00:37:12,800 THINK DEEPLY ABOUT HOW TO EVEN 920 00:37:12,800 --> 00:37:16,040 ILLUSTRATE THIS. 921 00:37:16,040 --> 00:37:17,640 IMAGINE FOR MOMENT THAT YOU HAVE 922 00:37:17,640 --> 00:37:18,920 A ROCK AND YOU'RE GOING TO GO 923 00:37:18,920 --> 00:37:20,800 OUT AND THROW THE ROCK INTO A 924 00:37:20,800 --> 00:37:21,560 PUDDLE OF WATER. 925 00:37:21,560 --> 00:37:23,640 YOU'RE GOING TO GET THIS FIGURE 926 00:37:23,640 --> 00:37:27,800 THAT LOOKS LIKE UP HERE AT THE 927 00:37:27,800 --> 00:37:29,200 TOP, THIS SET OF WAVES THAT MOVE 928 00:37:29,200 --> 00:37:32,720 OUT FROM A PARTICULAR LOCATION. 929 00:37:32,720 --> 00:37:35,560 AND THINKING IN THOSE TERMS, YOU 930 00:37:35,560 --> 00:37:38,960 CAN BEGIN TO PARSE OUT HOW TO 931 00:37:38,960 --> 00:37:41,800 THINK ABOUT THESE WAVES AS THEY 932 00:37:41,800 --> 00:37:44,320 PASS THROUGH THE BRAIN, THAT IT 933 00:37:44,320 --> 00:37:47,600 IS, IN FACT, A TRAVELING WAVE, 934 00:37:47,600 --> 00:37:51,880 WHICH REMARKABLY ITS POSITION IS 935 00:37:51,880 --> 00:37:53,000 CORRELATED OR ITS POSITION IN 936 00:37:53,000 --> 00:37:55,280 TIME IS CORRELATED WITH THE PEW 937 00:37:55,280 --> 00:38:05,840 LPUPILLARY DIAMETER. 938 00:38:07,040 --> 00:38:09,880 SO YOU HAVE AREAS THAT ARE -- 939 00:38:09,880 --> 00:38:14,000 CAN BE SPACED OUT SUCH THAT IF 940 00:38:14,000 --> 00:38:15,240 THEY'RE ALL ON CIRCLE A, THEY'RE 941 00:38:15,240 --> 00:38:16,640 GOING TO BE SYNCHRONOUS, THERE'S 942 00:38:16,640 --> 00:38:19,480 GOING TO BE ZERO LINE 943 00:38:19,480 --> 00:38:24,440 COMMUNICATION. 944 00:38:24,440 --> 00:38:27,040 THERE CAN BE A LAG, AS YOU CAN 945 00:38:27,040 --> 00:38:28,600 SEE HERE, BUT POSITION VERSUS 946 00:38:28,600 --> 00:38:31,880 THIS MOVING THING, IT BECOMES A 947 00:38:31,880 --> 00:38:32,680 VERY IMPORTANT DETERMINANT OF 948 00:38:32,680 --> 00:38:35,320 HOW YOU THINK ABOUT THIS AND 949 00:38:35,320 --> 00:38:38,320 FINALLY, WHICH CAN EVEN COME 950 00:38:38,320 --> 00:38:39,920 AROUND TO ANTICORRELATIONS, 951 00:38:39,920 --> 00:38:41,200 WHICH WAS ANOTHER SURPRISING 952 00:38:41,200 --> 00:38:42,320 FINDING IN OUR WORK ON THE 953 00:38:42,320 --> 00:38:46,360 BRAIN. 954 00:38:46,360 --> 00:38:47,440 SO THINKING ABOUT THIS IN TIME 955 00:38:47,440 --> 00:38:49,840 ADDS TO THE RICHNESS OF THE 956 00:38:49,840 --> 00:38:51,200 UNDERSTANDING OF WHAT'S GOING ON 957 00:38:51,200 --> 00:38:52,520 HERE, AND OF COURSE YOU IMAGINE 958 00:38:52,520 --> 00:38:56,000 THINKING INTO THE FUTURE THAT 959 00:38:56,000 --> 00:38:58,280 DIFFERENCES IN TIMING WILL HAVE 960 00:38:58,280 --> 00:39:06,280 BHIBEHAVIORAL CONSEQUENCES. 961 00:39:06,280 --> 00:39:07,480 SO IF YOU THINK ABOUT THIS, AND 962 00:39:07,480 --> 00:39:08,960 AS I MENTIONED, IF YOU JUST LOOK 963 00:39:08,960 --> 00:39:12,120 AT THE BRAIN IN TERMS OF LOOKING 964 00:39:12,120 --> 00:39:14,160 FOR CORRELATIONS WITHIN THE 965 00:39:14,160 --> 00:39:16,280 BRAIN, WHAT YOU FIND IS, SAY YOU 966 00:39:16,280 --> 00:39:18,360 HAVE THIS SO-CALLED DEFAULT MODE 967 00:39:18,360 --> 00:39:19,160 NETWORK. 968 00:39:19,160 --> 00:39:22,040 AND YOU ALSO HAVE AREAS OF THE 969 00:39:22,040 --> 00:39:28,040 BRAIN THAT ARE ANTECORRELATED SO 970 00:39:28,040 --> 00:39:29,360 THE BRAIN IS GOING FROM TWO 971 00:39:29,360 --> 00:39:30,480 DIFFERENT STATES AS IT SITS 972 00:39:30,480 --> 00:39:32,520 THERE IN A RESTING FORMATION. 973 00:39:32,520 --> 00:39:36,280 SO THIS IS WHAT'S DEPICTED HERE. 974 00:39:36,280 --> 00:39:37,400 AND WHAT'S SO INTERESTING IS 975 00:39:37,400 --> 00:39:38,920 THAT THIS -- IT'S CUT OFF AT THE 976 00:39:38,920 --> 00:39:41,120 BOTTOM OF MY SCREEN, BUT THIS IS 977 00:39:41,120 --> 00:39:43,120 WORK FROM DAVID MCCORMICK'S 978 00:39:43,120 --> 00:39:46,920 LABORATORY LOOKING AT AROUSAL, 979 00:39:46,920 --> 00:39:53,520 AND LOOKING AT HIPPOCAMPAL 980 00:39:53,520 --> 00:39:54,920 RIPPLE STATE ACTIVITY. 981 00:39:54,920 --> 00:39:56,000 WHAT'S SO REMARKABLE ABOUT THIS 982 00:39:56,000 --> 00:40:02,160 FOR ME, ANYWAY, IS HOW THEY 983 00:40:02,160 --> 00:40:04,440 RESEMBLE THIS STATE CHANGES THAT 984 00:40:04,440 --> 00:40:05,640 ARE ONGOING WITHIN THE BRAIN ON 985 00:40:05,640 --> 00:40:10,920 THESE VERY, VERY LARGE SCALES. 986 00:40:10,920 --> 00:40:15,080 SO YOU MIGHT THINK, WELL, OKAY, 987 00:40:15,080 --> 00:40:16,720 WE'RE MOVING TOWARDS THINKING 988 00:40:16,720 --> 00:40:18,240 ABOUT BRAIN STATES AND THEIR 989 00:40:18,240 --> 00:40:20,120 EFFECT ON BEHAVIOR AND SO FORTH, 990 00:40:20,120 --> 00:40:22,760 AND YOU CAN ALMOST IMAGINE YOU 991 00:40:22,760 --> 00:40:24,520 HAVE AN ALOE CENTRIC, THAT IS, 992 00:40:24,520 --> 00:40:26,360 I'M PAYING ATTENTION TO THE 993 00:40:26,360 --> 00:40:27,680 WORLD AROUND ME, AND EGO 994 00:40:27,680 --> 00:40:27,920 CENTRIC. 995 00:40:27,920 --> 00:40:31,840 THIS IS AN ONGOING CYCLIC 996 00:40:31,840 --> 00:40:34,560 PHENOMENON IN THE NORMAL BRAIN 997 00:40:34,560 --> 00:40:36,880 ACTIVITY AND IS A VERY NICE 998 00:40:36,880 --> 00:40:39,640 EXPLANATION WHERE THE 999 00:40:39,640 --> 00:40:40,640 WELL-DOCUMENTED VARIABILITY IN 1000 00:40:40,640 --> 00:40:41,920 BEHAVIOR WHICH HAS BEEN OBSERVED 1001 00:40:41,920 --> 00:40:43,880 BY MANY PEOPLE OVER MANY, MANY 1002 00:40:43,880 --> 00:40:47,080 YEARS. 1003 00:40:47,080 --> 00:40:48,920 THIS IS -- OR THE NEXT THING, IT 1004 00:40:48,920 --> 00:40:51,120 PROVIDES KIND OF A UNIFORM 1005 00:40:51,120 --> 00:40:54,320 FRAMEWORK FOR INTRINSIC 1006 00:40:54,320 --> 00:40:56,360 ACTIVITY. 1007 00:40:56,360 --> 00:40:58,520 AND IS A LOGICAL WAY OF THINKING 1008 00:40:58,520 --> 00:41:00,200 ABOUT BRAIN STATE DYNAMICS. 1009 00:41:00,200 --> 00:41:03,880 IT'S KIND OF A STEPPING STONE IN 1010 00:41:03,880 --> 00:41:13,920 A VERY INTRIGUING WAY FORWARD. 1011 00:41:13,920 --> 00:41:16,240 NOW THE QUESTION, OF COURSE, 1012 00:41:16,240 --> 00:41:18,440 GOING BACK TO THE FMRI SIGNAL 1013 00:41:18,440 --> 00:41:19,760 ITSELF, THERE'S A METABOLIC 1014 00:41:19,760 --> 00:41:20,120 COMPONENT HERE. 1015 00:41:20,120 --> 00:41:22,920 THIS IS NEUROPHYSIOLOGY AND 1016 00:41:22,920 --> 00:41:25,520 METABOLISM, SO HOW DO THEY MEET 1017 00:41:25,520 --> 00:41:26,000 UP? 1018 00:41:26,000 --> 00:41:29,520 ARE THEY RELATED IN SOME WAY, 1019 00:41:29,520 --> 00:41:34,200 WHICH COULD BE VERY IMPORTANT. 1020 00:41:34,200 --> 00:41:36,520 SO JUST TO REMIND YOU THAT IF 1021 00:41:36,520 --> 00:41:37,600 YOU'RE LOOKING AT THE BOTTOM 1022 00:41:37,600 --> 00:41:40,160 HERE AND YOU'RE SEEING THIS 1023 00:41:40,160 --> 00:41:44,280 WAVING SIGNAL DOWN HERE, WHAT'S 1024 00:41:44,280 --> 00:41:45,400 REALLY HAPPENING IS YOU'RE 1025 00:41:45,400 --> 00:41:46,840 HAVING CHANGES IN GLYCOLYSIS 1026 00:41:46,840 --> 00:41:47,920 THAT ARE GREATER THAN THE 1027 00:41:47,920 --> 00:41:51,240 CHANGES IN OXYGEN CONSUMPTION 1028 00:41:51,240 --> 00:41:53,080 BETWEEN ACTIVATION AND 1029 00:41:53,080 --> 00:41:54,960 DEACTIVATION OR JUST OVER TIME 1030 00:41:54,960 --> 00:41:55,920 IN GENERAL. 1031 00:41:55,920 --> 00:41:59,240 SO THERE CLEARLY IS A METABOLIC 1032 00:41:59,240 --> 00:42:00,520 ACTIVITY ONGOING HERE THAT 1033 00:42:00,520 --> 00:42:01,640 INVOLVES THE CIRCULATION AS 1034 00:42:01,640 --> 00:42:06,880 WELL. 1035 00:42:06,880 --> 00:42:08,440 SO HOW MIGHT WE BEGIN TO IMAGINE 1036 00:42:08,440 --> 00:42:11,040 THAT THESE TWO END UP 1037 00:42:11,040 --> 00:42:11,920 COORDINATED? 1038 00:42:11,920 --> 00:42:13,320 AND I'VE BECOME A VERY BIG FAN 1039 00:42:13,320 --> 00:42:17,960 OF THE VIP INTERNEURON AS A 1040 00:42:17,960 --> 00:42:18,840 RESULT OF THIS. 1041 00:42:18,840 --> 00:42:21,560 SO IF I MAY HAVE THE NEXT SLIDE. 1042 00:42:21,560 --> 00:42:23,000 SO WHERE DOES THAT FIT INTO THIS 1043 00:42:23,000 --> 00:42:24,760 STORY? 1044 00:42:24,760 --> 00:42:26,840 WELL, FROM THE WORK OF PEOPLE 1045 00:42:26,840 --> 00:42:27,920 LIKE MIKE STRIKER AND OTHERS, 1046 00:42:27,920 --> 00:42:30,120 THE VIP INTERNEURON IS CRITICAL 1047 00:42:30,120 --> 00:42:34,040 IN AFFECTING NEURONAL GAIN IN 1048 00:42:34,040 --> 00:42:34,520 THE BRAIN. 1049 00:42:34,520 --> 00:42:39,440 AND IT DOES SO BY HITTING THE 1050 00:42:39,440 --> 00:42:41,160 SOMATOSTATIN INTERNEURON WHICH 1051 00:42:41,160 --> 00:42:45,120 DISINHIBITS THE PYRAMIDAL CELL. 1052 00:42:45,120 --> 00:42:46,680 WHAT WE TEND TO FORGET HERE IS 1053 00:42:46,680 --> 00:42:48,200 HOW THESE INTERNEURONS GOT THEIR 1054 00:42:48,200 --> 00:42:50,960 NAME. 1055 00:42:50,960 --> 00:42:53,360 VIP IS VASOINTESTINAL 1056 00:42:53,360 --> 00:42:55,320 POLYPEPTIDE, AND THIS IS 1057 00:42:55,320 --> 00:42:56,880 SOMATOSTA YOU TIN. 1058 00:42:56,880 --> 00:42:57,240 SOMATOSTATIN. 1059 00:42:57,240 --> 00:42:58,440 THESE ARE BOTH VERY IMPORTANT 1060 00:42:58,440 --> 00:43:01,280 PROTEINS. 1061 00:43:01,280 --> 00:43:06,920 HIGHLY NEGLECTED. 1062 00:43:06,920 --> 00:43:08,160 WHAT DO WE KNOW ABOUT THE OTHER 1063 00:43:08,160 --> 00:43:09,360 ARM OF VIP? 1064 00:43:09,360 --> 00:43:14,960 SO WHILE IT INCREASES GAIN, IT 1065 00:43:14,960 --> 00:43:19,800 INFLUENCES THE ASTROCYTE TO 1066 00:43:19,800 --> 00:43:30,280 DEVELOP GLYCOGENOLOSIS, DEEPLY 1067 00:43:33,000 --> 00:43:36,000 IMPORTANT WORK OVER TIME IS THAT 1068 00:43:36,000 --> 00:43:40,160 A ACUTE CHANGE IN NEURONAL 1069 00:43:40,160 --> 00:43:41,960 ACTIVITY IS LARGELY FUELED BY 1070 00:43:41,960 --> 00:43:45,200 LACTATE AND THE ATP PRODUCED. 1071 00:43:45,200 --> 00:43:46,960 WHICH GOES BACK TO THE WHOLE 1072 00:43:46,960 --> 00:43:49,200 STORY THAT I TALKED ABOUT IN THE 1073 00:43:49,200 --> 00:43:52,000 CONTEXT OF THE DEVELOPMENT OF 1074 00:43:52,000 --> 00:43:54,760 FMRI, BUT IT HAS BIOLOGICAL 1075 00:43:54,760 --> 00:43:55,760 CONSEQUENCES AS WELL. 1076 00:43:55,760 --> 00:43:57,760 BUT THIS IS A BEAUTIFUL 1077 00:43:57,760 --> 00:44:00,560 DEMONSTRATION OF PROVIDING THE 1078 00:44:00,560 --> 00:44:01,800 NECESSARY FUEL FOR A SUDDEN 1079 00:44:01,800 --> 00:44:04,360 CHANGE IN ACTIVITY THAT IS 1080 00:44:04,360 --> 00:44:06,520 LIKELY TO BE CONSEQUENCES OF A 1081 00:44:06,520 --> 00:44:09,480 CHANGE IN THE GAIN OF A 1082 00:44:09,480 --> 00:44:10,040 PYRAMIDAL CELL. 1083 00:44:10,040 --> 00:44:11,480 AND I THINK IT ILLUSTRATES HOW 1084 00:44:11,480 --> 00:44:15,320 WE WOULD BEGIN TO THINK ABOUT 1085 00:44:15,320 --> 00:44:19,560 THESE RELATIONSHIPS AS BOTH 1086 00:44:19,560 --> 00:44:20,960 METABOLIC AND 1087 00:44:20,960 --> 00:44:21,600 NEUROPHYSIOLOGICAL, AND THEY 1088 00:44:21,600 --> 00:44:23,840 HAVE TO BE ADDRESSED TOGETHER TO 1089 00:44:23,840 --> 00:44:31,520 MAKE THIS THING WORK RIGHT. 1090 00:44:31,520 --> 00:44:33,160 THE OTHER THING THAT I THINK IS 1091 00:44:33,160 --> 00:44:34,480 DEEPLY IMPORTANT HERE IS THAT 1092 00:44:34,480 --> 00:44:36,600 THE BRAIN ISN'T ALONE IN THIS 1093 00:44:36,600 --> 00:44:39,520 JOB, THAT WHAT IS GOING ON HERE 1094 00:44:39,520 --> 00:44:42,400 METABOLICALLY AND HORMONALLY AND 1095 00:44:42,400 --> 00:44:46,760 OTHERWISE IS RELATED TO THIS 1096 00:44:46,760 --> 00:44:48,840 WHOLE ISSUE OF AROUSAL, WHETHER 1097 00:44:48,840 --> 00:44:54,920 IT FIGHT OR FLIGHT OR REST AND 1098 00:44:54,920 --> 00:44:55,280 DIGESTION. 1099 00:44:55,280 --> 00:44:57,000 AND I THINK THE THING THAT HAS 1100 00:44:57,000 --> 00:44:58,080 CAPTURED THIS BETTER THAN 1101 00:44:58,080 --> 00:44:59,960 ANYTHING I KNOW IS THE WHOLE 1102 00:44:59,960 --> 00:45:06,000 NOTION OF AL ALLOSTASIS, WHICH A 1103 00:45:06,000 --> 00:45:08,200 BRAIN CENTERED PREDICTIVE MODE 1104 00:45:08,200 --> 00:45:09,840 OF PHYSIOLOGICAL REGULATION, 1105 00:45:09,840 --> 00:45:10,840 FIRST PUT FORWARD BY PETER 1106 00:45:10,840 --> 00:45:11,360 STERLING. 1107 00:45:11,360 --> 00:45:13,440 THE BRAIN HAS TO OPERATE IN AN 1108 00:45:13,440 --> 00:45:15,640 ENVIRONMENT IN WHICH IT HAS TO 1109 00:45:15,640 --> 00:45:17,800 ANTICIPATE CHANGING CONDITIONS 1110 00:45:17,800 --> 00:45:20,920 AND ADJUST ITSELF FOR THAT. 1111 00:45:20,920 --> 00:45:24,400 AND THIS IS A MAJOR TALK OF ITS 1112 00:45:24,400 --> 00:45:26,800 OWN, SO I'M NOT GOING TO BELABOR 1113 00:45:26,800 --> 00:45:28,760 THIS POINT, BUT AS WE THINK OF 1114 00:45:28,760 --> 00:45:30,640 THE BRAIN AND ITS DEALING WITH 1115 00:45:30,640 --> 00:45:33,840 THE WORLD IN WHICH WE LIVE, AND 1116 00:45:33,840 --> 00:45:37,240 PROVIDING THE ADEQUATE ENERGY TO 1117 00:45:37,240 --> 00:45:39,240 ACCOMPLISH WHAT NEEDS TO BE 1118 00:45:39,240 --> 00:45:42,960 ACCOMPLISHED, IT IS A BRAIN BODY 1119 00:45:42,960 --> 00:45:45,120 PROBLEM THAT INVOLVES METABOLISM 1120 00:45:45,120 --> 00:45:48,120 AS WELL AS NEUROPHYSIOLOGY, AND 1121 00:45:48,120 --> 00:45:49,880 IS A VERY IMPORTANT AREA OF 1122 00:45:49,880 --> 00:45:56,640 FUTURE RESEARCH. 1123 00:45:56,640 --> 00:45:57,920 WE MIGHT SAY A LITTLE BIT ABOUT 1124 00:45:57,920 --> 00:45:59,080 DISEASE OR MUCH THAT COULD BE 1125 00:45:59,080 --> 00:46:00,400 SAID, MUCH THAT HAS BEEN 1126 00:46:00,400 --> 00:46:01,480 WRITTEN, BUT I WOULD JUST LIKE 1127 00:46:01,480 --> 00:46:03,800 TO GIVE A QUICK EXAMPLE OF ONE 1128 00:46:03,800 --> 00:46:06,080 CONDITION IN WHICH IF YOU PUT IT 1129 00:46:06,080 --> 00:46:08,080 IN THE FRAMEWORK OF MUCH OF WHAT 1130 00:46:08,080 --> 00:46:12,920 I'VE SAID, YOU FIND THAT YOUR 1131 00:46:12,920 --> 00:46:15,560 PERSPECTIVE IS ENLARGED AS YOU 1132 00:46:15,560 --> 00:46:22,560 THINK ABOUT IT THIS WAY. 1133 00:46:22,560 --> 00:46:28,160 SO WE HAVE, IN ACTIVITY 1134 00:46:28,160 --> 00:46:29,480 DECREASES AND SPONTANEOUS 1135 00:46:29,480 --> 00:46:33,960 ACTIVITY, WE SEE IT HAS ELEVATED 1136 00:46:33,960 --> 00:46:37,240 GLYCOLYSIS, THIS IS THIS SO CA 1137 00:46:37,240 --> 00:46:38,040 CALLED DEFAULT NETWORK. 1138 00:46:38,040 --> 00:46:40,800 IF YOU LOOK AT THE DISEASE, YOU 1139 00:46:40,800 --> 00:46:43,320 SEE THE REMARKABLE 1140 00:46:43,320 --> 00:46:45,080 REPRESENTATION OF THE AMYLOID 1141 00:46:45,080 --> 00:46:46,400 DEPOSITS, THE DECREASE IN 1142 00:46:46,400 --> 00:46:48,120 METABOLISM AND THE ATROPHY IS 1143 00:46:48,120 --> 00:46:49,160 THE SAME. 1144 00:46:49,160 --> 00:46:52,120 AND I THINK WHAT THIS DOES, IT 1145 00:46:52,120 --> 00:46:53,960 SAYS, OKAY, WE HAVE A PROBLEM 1146 00:46:53,960 --> 00:46:56,520 HERE, A MEMORY DISORDER 1147 00:46:56,520 --> 00:46:59,360 INVOLVING THE DEFAULT NETWORK, 1148 00:46:59,360 --> 00:47:01,440 WHICH IS INCLUDED WITH THE 1149 00:47:01,440 --> 00:47:04,080 HIPPOCAMPUS IN A SO-CALLED 1150 00:47:04,080 --> 00:47:05,280 HIPPOCAMPAL CORTICAL MEMORY 1151 00:47:05,280 --> 00:47:07,360 SYSTEM, BUT WE KNEW A LOT ABOUT 1152 00:47:07,360 --> 00:47:10,800 THAT FROM THE NEUROPHYSIOLOGY 1153 00:47:10,800 --> 00:47:12,880 HERE THAT WOULD, I THINK, HELP 1154 00:47:12,880 --> 00:47:15,720 US A GREAT DEAL IN UNDERSTANDING 1155 00:47:15,720 --> 00:47:18,120 THE NUMBER OF POSSIBILITIES THAT 1156 00:47:18,120 --> 00:47:21,880 HAVE GONE WRONG IN THIS 1157 00:47:21,880 --> 00:47:24,080 BEAUTIFUL RELATIONSHIP INVOLVING 1158 00:47:24,080 --> 00:47:26,560 THE NEUROPHYSIOLOGY OF THE 1159 00:47:26,560 --> 00:47:28,360 MEMORY SYSTEM AND THE METABOLISM 1160 00:47:28,360 --> 00:47:30,520 THAT SUPPORTS IT, AND THE ROLE 1161 00:47:30,520 --> 00:47:33,280 OF THINGS LIKE AMYLOID AND TAU, 1162 00:47:33,280 --> 00:47:36,280 THESE PROTEINS THAT ARE CRITICAL 1163 00:47:36,280 --> 00:47:37,160 TO THIS. 1164 00:47:37,160 --> 00:47:39,000 I'M LEAVING A SUBJECT THAT 1165 00:47:39,000 --> 00:47:41,600 OBVIOUSLY COULD BE A LECTURE AND 1166 00:47:41,600 --> 00:47:46,920 A HALF, BUT I THINK IT ALLOWS US 1167 00:47:46,920 --> 00:47:50,040 TO FRAME WITH THIS INCREASED 1168 00:47:50,040 --> 00:47:51,480 KNOWLEDGE OF HOW THE BRAIN IS 1169 00:47:51,480 --> 00:47:54,240 ORGANIZED FUNCTIONALLY AND 1170 00:47:54,240 --> 00:47:55,600 METABOLICALLY, IT OPENS 1171 00:47:55,600 --> 00:48:00,720 OPPORTUNITIES FOR US TO BE MORE 1172 00:48:00,720 --> 00:48:01,920 SOPHISTICATED IN HOW WE 1173 00:48:01,920 --> 00:48:02,600 UNDERSTAND THEM. 1174 00:48:02,600 --> 00:48:05,120 SO FINAL SLIDE, I THINK. 1175 00:48:05,120 --> 00:48:08,880 I JUST LOVE THIS COMMENT BY 1176 00:48:08,880 --> 00:48:10,640 RODOLFO LLINAS WHEN HE SAID IN 1177 00:48:10,640 --> 00:48:15,240 HIS BOOK, THE SIGNIFICANCE OF 1178 00:48:15,240 --> 00:48:16,160 INCOMING SENSORY INFORMATION 1179 00:48:16,160 --> 00:48:17,560 DEPENDS ON THE PRE-EXISTING 1180 00:48:17,560 --> 00:48:19,520 DISPOSITION OF THE BRAIN, IS A 1181 00:48:19,520 --> 00:48:21,960 FAR DEEPER ISSUE THAN ONE 1182 00:48:21,960 --> 00:48:24,600 GATHERS AT FIRST GLANCE, 1183 00:48:24,600 --> 00:48:26,240 PARTICULARLY WHEN WE LOOK INTO 1184 00:48:26,240 --> 00:48:28,440 THE QUESTION OF SELF. 1185 00:48:28,440 --> 00:48:31,400 THANK YOU VERY MUCH. 1186 00:48:31,400 --> 00:48:32,880 >>OKAY. 1187 00:48:32,880 --> 00:48:38,160 THANK YOU VERY, VERY MUCH FOR AN 1188 00:48:38,160 --> 00:48:39,720 INTRODUCTION FOO THE EXCITING 1189 00:48:39,720 --> 00:48:43,360 WORLD IN WHICH YOU SPEND YOUR 1190 00:48:43,360 --> 00:48:44,880 CAREER. 1191 00:48:44,880 --> 00:48:48,600 SO NOW WE WANT TO TURN MORE TO 1192 00:48:48,600 --> 00:48:52,000 OUR CELLS AND MOLECULES. 1193 00:48:52,000 --> 00:48:53,560 AND NELSON, WOULD YOU PLEASE 1194 00:48:53,560 --> 00:48:55,760 BEGIN? 1195 00:48:55,760 --> 00:48:57,240 >>YES, THANK YOU VERY MUCH FOR 1196 00:48:57,240 --> 00:48:59,560 THE INVITATION TO BE HERE THIS 1197 00:48:59,560 --> 00:49:01,200 AFTERNOON. 1198 00:49:01,200 --> 00:49:02,480 AND ADDRESS THE SIMPLE QUESTION, 1199 00:49:02,480 --> 00:49:05,280 HOW DO THE BRAIN WORK? 1200 00:49:05,280 --> 00:49:06,960 I'M GOING TO DO MY BEST TO TELL 1201 00:49:06,960 --> 00:49:08,480 YOU A LITTLE BIT ABOUT WHAT WE 1202 00:49:08,480 --> 00:49:10,560 KNOW ABOUT HOW THE BRAIN WORKS. 1203 00:49:10,560 --> 00:49:11,840 AND NOT KNOWING THE AUDIENCE 1204 00:49:11,840 --> 00:49:12,880 VERY WELL, IT'S DIFFICULT TO 1205 00:49:12,880 --> 00:49:14,320 GAUGE WHAT KIND OF A LEVEL I 1206 00:49:14,320 --> 00:49:15,520 SHOULD BE SPEAKING AT, SO I'M 1207 00:49:15,520 --> 00:49:18,600 GOING TO TRY TO COVER A BUNCH OF 1208 00:49:18,600 --> 00:49:20,280 GROUND HERE AND LOOK FORWARD TO 1209 00:49:20,280 --> 00:49:24,440 THE QUESTION AND ANSWER. 1210 00:49:24,440 --> 00:49:26,320 SO I WAS ASKED TO PROVIDE THESE 1211 00:49:26,320 --> 00:49:27,560 DISCLOSURES, I DON'T HAVE ANY 1212 00:49:27,560 --> 00:49:28,320 SIGNIFICANT CONFLICTS OF 1213 00:49:28,320 --> 00:49:28,640 INTEREST. 1214 00:49:28,640 --> 00:49:30,640 LEARNING OBJECTIVES IS TO 1215 00:49:30,640 --> 00:49:31,840 ACHIEVE A BASIC UNDERSTANDING OF 1216 00:49:31,840 --> 00:49:32,920 THE COMPOSITION AND FUNCTION OF 1217 00:49:32,920 --> 00:49:34,040 THE NERVOUS SYSTEM AND THE 1218 00:49:34,040 --> 00:49:35,280 DESCRIPTION OF MODERN APPROACHES 1219 00:49:35,280 --> 00:49:37,880 TO STUDYING THE BRAIN AT THE 1220 00:49:37,880 --> 00:49:39,000 CELLULAR, SYNAPTIC AND CIRCUIT 1221 00:49:39,000 --> 00:49:39,640 LEVELS. 1222 00:49:39,640 --> 00:49:42,080 SO I GOT INTERESTED IN 1223 00:49:42,080 --> 00:49:47,040 NEUROSCIENCE AS AN UNDERGRADUATE 1224 00:49:47,040 --> 00:49:48,200 LARGELY BECAUSE I WAS FASCINATED 1225 00:49:48,200 --> 00:49:49,800 WITH THE CONCEPT OF MEMORY, THAT 1226 00:49:49,800 --> 00:49:50,880 SOMETHING COULD HAPPEN TO US ONE 1227 00:49:50,880 --> 00:49:51,960 TIME AND WE COULD REMEMBER IT 1228 00:49:51,960 --> 00:49:53,640 YEARS LATER. 1229 00:49:53,640 --> 00:49:55,400 I NOW REALIZE THAT MEMORY IS 1230 00:49:55,400 --> 00:49:57,240 EVEN MORE FASCINATING BECAUSE 1231 00:49:57,240 --> 00:49:59,440 THE OLDER I GET, THE LONGER I 1232 00:49:59,440 --> 00:50:00,680 CAN STORE THOSE MEMORIES AND 1233 00:50:00,680 --> 00:50:01,560 REALIZE THAT I CAN REMEMBER 1234 00:50:01,560 --> 00:50:03,160 THINGS THAT HAPPENED TO ME 1235 00:50:03,160 --> 00:50:04,600 DECADES AGO. 1236 00:50:04,600 --> 00:50:06,160 AND I'VE THOUGHT IT WAS A 1237 00:50:06,160 --> 00:50:08,240 FASCINATING QUESTION HOW DOES 1238 00:50:08,240 --> 00:50:10,120 THIS STUFF INSIDE OF OUR SKULL 1239 00:50:10,120 --> 00:50:11,560 MAKE THIS POSSIBLE. 1240 00:50:11,560 --> 00:50:15,160 AND THIS LED ME TO STUDY THE 1241 00:50:15,160 --> 00:50:18,240 HIPPOCAMPUS BECAUSE THERE ARE 1242 00:50:18,240 --> 00:50:19,360 MANY PATIENTS THAT HAVE SUFFERED 1243 00:50:19,360 --> 00:50:22,880 DAMAGE TO THE HIPPOCAMPUS 1244 00:50:22,880 --> 00:50:23,720 BILATERALLY AND HAVE VERY 1245 00:50:23,720 --> 00:50:25,480 INTERESTING IMPAIRMENTS OF THEIR 1246 00:50:25,480 --> 00:50:26,320 MEMORY, SPECIFICALLY IMPAIRMENTS 1247 00:50:26,320 --> 00:50:27,920 OF THE TYPES OF MEMORIES THAT 1248 00:50:27,920 --> 00:50:29,680 THEY CAN TALK ABOUT CALLED 1249 00:50:29,680 --> 00:50:30,760 EPISODIC MEMORIES. 1250 00:50:30,760 --> 00:50:32,840 AND THOSE DEFICITS INCLUDE 1251 00:50:32,840 --> 00:50:35,920 LARGELY AN INABILITY TO FORM NEW 1252 00:50:35,920 --> 00:50:37,800 MEMORIES, YET AN ABILITY TO 1253 00:50:37,800 --> 00:50:39,200 RECALL SOME OF THEIR OLDER 1254 00:50:39,200 --> 00:50:39,480 MEMORIES. 1255 00:50:39,480 --> 00:50:42,640 AND THE REASON FOR THIS IS THE 1256 00:50:42,640 --> 00:50:44,920 GENERAL THINKING HERE IS THAT 1257 00:50:44,920 --> 00:50:47,040 THERE ARE COMPLIMENTARY LEARNING 1258 00:50:47,040 --> 00:50:47,680 SYSTEMS. 1259 00:50:47,680 --> 00:50:49,040 THE HIPPOCAMPUS IS A FAST 1260 00:50:49,040 --> 00:50:50,400 LEARNING SYSTEM WHICH CAPTURES 1261 00:50:50,400 --> 00:50:54,280 OUR EXPERIENCES RIGHT AWAY, AND 1262 00:50:54,280 --> 00:50:55,120 THEN OVER TIME, THOSE 1263 00:50:55,120 --> 00:50:56,600 EXPERIENCES ARE REPLAYED AND 1264 00:50:56,600 --> 00:50:59,320 LEARNED OR STORED IN THIS LARGER 1265 00:50:59,320 --> 00:51:00,760 OVERLYING NEOCORTEX THAT YOU SEE 1266 00:51:00,760 --> 00:51:03,720 HERE IN THE HUMAN BRAIN. 1267 00:51:03,720 --> 00:51:04,920 SO THE INTERESTING QUESTION FOR 1268 00:51:04,920 --> 00:51:08,960 ME IS, HOW DOES THIS -- HOW DO 1269 00:51:08,960 --> 00:51:10,360 MEMORIES GET CAPTURED BY THE 1270 00:51:10,360 --> 00:51:11,880 HIPPOCAMPUS AND HOW DOES THIS 1271 00:51:11,880 --> 00:51:13,600 REPLAY SYSTEM ALLOW THE 1272 00:51:13,600 --> 00:51:14,960 NEOCORTEX TO LEARN FROM THOSE 1273 00:51:14,960 --> 00:51:20,120 STORED MEMORIES AND HIPPOCAMPUS. 1274 00:51:20,120 --> 00:51:21,640 AND EARLY ON IN MY TRAINING, I 1275 00:51:21,640 --> 00:51:22,960 BECAME FASCINATED WITH THE 1276 00:51:22,960 --> 00:51:24,280 STRUCTURE OF NEURONS, AND IT 1277 00:51:24,280 --> 00:51:28,040 BECAME APPARENT TO ME THAT A KEY 1278 00:51:28,040 --> 00:51:28,880 TO UNDERSTANDING THIS QUESTION 1279 00:51:28,880 --> 00:51:30,280 OF HOW DOES THE BRAIN WORK OR 1280 00:51:30,280 --> 00:51:32,880 HOW ARE MEMORIES STORED IS TO 1281 00:51:32,880 --> 00:51:34,080 UNDERSTAND SOMETHING ABOUT THE 1282 00:51:34,080 --> 00:51:35,160 RELATIONSHIP BETWEEN THE 1283 00:51:35,160 --> 00:51:36,720 STRUCTURE AND THE FUNCTION OF 1284 00:51:36,720 --> 00:51:37,200 NEURONS. 1285 00:51:37,200 --> 00:51:39,920 THESE ARE JUST SOME EXAMPLES, 1286 00:51:39,920 --> 00:51:44,360 BEAUTIFUL DRAWINGS MADE BY 1287 00:51:44,360 --> 00:51:47,720 SANTIAGO CAJAL ABOUT A HUNDRED 1288 00:51:47,720 --> 00:51:48,920 YEARS AGO SHOWING NEURONS IN 1289 00:51:48,920 --> 00:51:50,440 DIFFERENT PARTS OF THE BRAIN, 1290 00:51:50,440 --> 00:51:51,760 AND YOU CAN SEE THAT THEY HAVE 1291 00:51:51,760 --> 00:51:54,960 TWO REALLY STRIKING FEATURES. 1292 00:51:54,960 --> 00:51:58,400 ONE IS A VERY LARGE ELABORATED 1293 00:51:58,400 --> 00:51:58,760 DENDRITIC TREE. 1294 00:51:58,760 --> 00:52:01,880 YOU CAN THINK OF DENDRITIC TREES 1295 00:52:01,880 --> 00:52:03,080 AS PART OF THE NEURON THAT 1296 00:52:03,080 --> 00:52:04,480 RECEIVES INPUT FROM OTHER 1297 00:52:04,480 --> 00:52:05,760 NEURONS, AND THEN THE AXON, 1298 00:52:05,760 --> 00:52:07,840 WHICH USUALLY EMERGES FROM THE 1299 00:52:07,840 --> 00:52:10,400 CELL BODY HERE, AND THE AXON, 1300 00:52:10,400 --> 00:52:11,520 YOU CAN THINK OF AS THE 1301 00:52:11,520 --> 00:52:12,640 STRUCTURE THAT PROVIDES OUTPUT 1302 00:52:12,640 --> 00:52:14,600 FROM THE NEURON, AND 1303 00:52:14,600 --> 00:52:15,800 COMMUNICATES WITH OTHER NEURONS 1304 00:52:15,800 --> 00:52:19,080 IN THE BRAIN. 1305 00:52:19,080 --> 00:52:20,520 THIS IS ANOTHER BEAUTIFUL SLIDE. 1306 00:52:20,520 --> 00:52:23,080 THIS WAS ASSEMBLED BY ONE OF MY 1307 00:52:23,080 --> 00:52:27,560 COLLEAGUES, BARTLETT MEL AT USC. 1308 00:52:27,560 --> 00:52:29,440 HE COLLECTED DRAWINGS OF THE 1309 00:52:29,440 --> 00:52:31,080 DENDRITIC TREE OF MANY DIFFERENT 1310 00:52:31,080 --> 00:52:33,200 NEURONS AND FROM VARIOUS 1311 00:52:33,200 --> 00:52:34,480 PUBLICATIONS AND HIS GOAL WAS TO 1312 00:52:34,480 --> 00:52:37,040 SORT OF ILLUSTRATE HOW DIVERSE 1313 00:52:37,040 --> 00:52:39,040 THE DENDRITIC TREES ARE OF 1314 00:52:39,040 --> 00:52:40,000 DIFFERENT TYPES OF NEURONS. 1315 00:52:40,000 --> 00:52:42,520 IT TURNS OUT THAT WE KNOW THAT 1316 00:52:42,520 --> 00:52:44,520 ALONG WITH THE COMPLEXITY AND 1317 00:52:44,520 --> 00:52:46,320 DIVERSITY OF THE MORPHOLOGY OF 1318 00:52:46,320 --> 00:52:48,080 NEURONS AS DEPICTED HERE, 1319 00:52:48,080 --> 00:52:50,400 THERE'S A COMPLEMENTARY 1320 00:52:50,400 --> 00:52:52,280 DIVERSITY IN THE MOLECULAR 1321 00:52:52,280 --> 00:52:53,920 COMPOSITION AND THE 1322 00:52:53,920 --> 00:52:54,600 PHYSIOLOGICAL PROPERTIES OF 1323 00:52:54,600 --> 00:52:55,440 THESE DIFFERENT TYPES OF 1324 00:52:55,440 --> 00:52:56,560 NEURONS. 1325 00:52:56,560 --> 00:52:58,640 SO ONE OF THE KEYS, I THINK, TO 1326 00:52:58,640 --> 00:52:59,560 UNDERSTANDING HOW THE BRAIN 1327 00:52:59,560 --> 00:53:02,400 WORKS IS TO UNDERSTAND WHAT KIND 1328 00:53:02,400 --> 00:53:05,560 OF COMPUTATIONS ARE BEING 1329 00:53:05,560 --> 00:53:06,240 PERFORMED PHYSIOLOGICALLY BY 1330 00:53:06,240 --> 00:53:07,760 THESE NEURONS THAT HAVE THESE 1331 00:53:07,760 --> 00:53:08,880 AMAZING STRUCTURES? 1332 00:53:08,880 --> 00:53:13,040 AND DENDRITES PLAY A SUPER 1333 00:53:13,040 --> 00:53:14,200 IMPORTANT ROLE IN THAT PROCESS 1334 00:53:14,200 --> 00:53:16,480 WHICH IS WHY FOR A COUPLE OF 1335 00:53:16,480 --> 00:53:18,880 DECADES, I STUDIED DENDRITES 1336 00:53:18,880 --> 00:53:19,920 INTENSIVELY IN MY OWN LAB. 1337 00:53:19,920 --> 00:53:21,760 HERE'S A PICTURE FROM SOME WORK 1338 00:53:21,760 --> 00:53:24,040 WE PUBLISHED SEVERAL YEARS AGO 1339 00:53:24,040 --> 00:53:25,160 NOW FROM MY OWN LAB. 1340 00:53:25,160 --> 00:53:27,840 THIS IS A NUMBER OF PYRAMIDAL 1341 00:53:27,840 --> 00:53:29,360 NEAR ONS IN HIPPOCAMPUS, WHICH 1342 00:53:29,360 --> 00:53:31,000 ARE SHOWN HERE IN GREEN, AND 1343 00:53:31,000 --> 00:53:34,280 THEN THERE ARE SOME AXONS OF 1344 00:53:34,280 --> 00:53:35,280 INHIBITORY INTERNEURONS SHOWN 1345 00:53:35,280 --> 00:53:37,040 HERE IN RED, AND I THINK THIS 1346 00:53:37,040 --> 00:53:39,320 NICELY DEPICTS THE STRUCTURAL 1347 00:53:39,320 --> 00:53:42,640 COMPLEXITY OF NEURONS IN THE 1348 00:53:42,640 --> 00:53:45,680 HIPPOCAMPUS AND DR. REICHLE 1349 00:53:45,680 --> 00:53:47,560 REFERRED TO VIP INTERNEURONS. 1350 00:53:47,560 --> 00:53:48,480 THEY'RE ONE OF MANY DIFFERENT 1351 00:53:48,480 --> 00:53:50,440 TYPES OF INHIBITORY INTERNEURONS 1352 00:53:50,440 --> 00:53:52,320 THROUGHOUT THE BRAIN, EVEN IN 1353 00:53:52,320 --> 00:53:52,880 THE HIPPOCAMPUS, THERE ARE 1354 00:53:52,880 --> 00:53:54,600 THOUGHT TO BE AT LEAST A COUPLE 1355 00:53:54,600 --> 00:53:55,920 DOZEN DIFFERENT TYPES OF 1356 00:53:55,920 --> 00:53:59,640 INHIBITORY INTERNEURONS. 1357 00:53:59,640 --> 00:54:01,760 I WANT TO TURN TO THE AXON, 1358 00:54:01,760 --> 00:54:03,200 BECAUSE A LOT OF WHAT WE'VE SEEN 1359 00:54:03,200 --> 00:54:06,680 OF PICTURES OF NEURONS FOCUSES 1360 00:54:06,680 --> 00:54:08,360 ON DENDRITES, BUT ACTUALLY AXONS 1361 00:54:08,360 --> 00:54:09,440 ARE QUITE FASCINATING. 1362 00:54:09,440 --> 00:54:10,800 AND THIS WAS A VIDEO THAT WAS 1363 00:54:10,800 --> 00:54:12,840 PUT TOGETHER BY THE MOUSELIGHT 1364 00:54:12,840 --> 00:54:14,640 PROJECT TEAM HERE AT JE KNEEL YA 1365 00:54:14,640 --> 00:54:19,040 -- ATJANELIA WHERE I WORK, ANDS 1366 00:54:19,040 --> 00:54:20,480 IS A PROJECT THAT USED A NEW 1367 00:54:20,480 --> 00:54:23,120 MICROSCOPE THAT INVOLVED 1368 00:54:23,120 --> 00:54:25,480 CLEARING, STAINING A FEW NEURONS 1369 00:54:25,480 --> 00:54:26,520 IN THE BRAIN AND THEN CLEARING 1370 00:54:26,520 --> 00:54:28,080 THE TISSUE TO MAKE IT AS CLEAR 1371 00:54:28,080 --> 00:54:30,760 AS POSSIBLE AND IMAGING IT WITH 1372 00:54:30,760 --> 00:54:33,280 A 2 PHOTON MICROSCOPE THAT 1373 00:54:33,280 --> 00:54:34,920 IMAGES THE SURFACE OF THE TISSUE 1374 00:54:34,920 --> 00:54:36,280 AND THEN SECTIONED IT AWAY, 1375 00:54:36,280 --> 00:54:37,720 IMAGED THE SURFACE OF THE TISSUE 1376 00:54:37,720 --> 00:54:39,000 AGAIN, AND SO ON THROUGH THE 1377 00:54:39,000 --> 00:54:41,480 ENTIRE VOLUME OF THE BRAIN. 1378 00:54:41,480 --> 00:54:43,240 AND THEN COMPUTATIONAL METHODS 1379 00:54:43,240 --> 00:54:44,840 WERE USED TO STITCH TOGETHER THE 1380 00:54:44,840 --> 00:54:46,840 MANY IMAGES THAT WERE COLLECTED 1381 00:54:46,840 --> 00:54:50,600 FROM THIS APPROACH, AND A 1382 00:54:50,600 --> 00:54:52,280 RECONSTRUCTION EFFORT WAS 1383 00:54:52,280 --> 00:54:54,880 UNDERTAKEN TO RECONSTRUCT AXONS 1384 00:54:54,880 --> 00:54:56,160 OF MANY DIFFERENT NEURONS. 1385 00:54:56,160 --> 00:54:58,120 SO NOW WHAT YOU'RE SEEING RIGHT 1386 00:54:58,120 --> 00:55:04,240 NOW IS AN AXON OF A SINGLE 1387 00:55:04,240 --> 00:55:07,040 NEURON THAT'S BEEN RECONSTRUCTED 1388 00:55:07,040 --> 00:55:08,800 THROUGH YON THE MOUSE BRAIN AND 1389 00:55:08,800 --> 00:55:10,200 THE REST OF THE VIDEO WHICH WILL 1390 00:55:10,200 --> 00:55:11,960 GO ON FOR ANOTHER MINUTE OR TWO 1391 00:55:11,960 --> 00:55:13,280 WILL SHOW YOU MANY OTHER 1392 00:55:13,280 --> 00:55:14,320 EXAMPLES OF NEURONS AND I'LL 1393 00:55:14,320 --> 00:55:15,480 POINT TO SOME OF THE FEATURES AS 1394 00:55:15,480 --> 00:55:18,920 IT PLAYS. 1395 00:55:18,920 --> 00:55:21,120 WE'RE GOING TO NEXT LOOK AT SOME 1396 00:55:21,120 --> 00:55:22,440 NEURONS IN THE SOMATOMOTOR AREA. 1397 00:55:22,440 --> 00:55:23,600 THIS IS ALL DONE IN THE MOUSE 1398 00:55:23,600 --> 00:55:24,240 BRAIN. 1399 00:55:24,240 --> 00:55:25,560 SO MUCH OF WHAT WE KNOW ABOUT 1400 00:55:25,560 --> 00:55:27,520 THE BASIC PHYSIOLOGY IS STUDIED 1401 00:55:27,520 --> 00:55:30,680 IN MICE AND RATS AS WELL AS 1402 00:55:30,680 --> 00:55:32,600 OTHER ORGANISMS LIKE FISH AND 1403 00:55:32,600 --> 00:55:32,920 FLIES. 1404 00:55:32,920 --> 00:55:34,520 THESE ARE JUST THREE NEURONS, 1405 00:55:34,520 --> 00:55:36,520 AND YOU CAN SEE THE AMAZING 1406 00:55:36,520 --> 00:55:38,880 ELABORATION OF THE AXON 1407 00:55:38,880 --> 00:55:40,520 ARBORIZATIONS OF THESE THREE 1408 00:55:40,520 --> 00:55:42,000 NEURONS, SO JUST THREE NEURONS 1409 00:55:42,000 --> 00:55:44,080 IN THE MOUSE BRAIN CONSTITUTE 1410 00:55:44,080 --> 00:55:46,280 OVER A METER OF AXON THAT'S 1411 00:55:46,280 --> 00:55:47,840 CONTAINED WITHIN THE SKULL OF 1412 00:55:47,840 --> 00:55:51,040 THIS ANIMAL. 1413 00:55:51,040 --> 00:55:52,560 THESE ARE JUST A HANDFUL OF 1414 00:55:52,560 --> 00:55:53,120 NEURONS. 1415 00:55:53,120 --> 00:55:55,040 EACH MOUSE BRAIN CONTAINS 1416 00:55:55,040 --> 00:55:55,800 70 MILLION NEURONS. 1417 00:55:55,800 --> 00:55:58,400 HUMAN BRAIN CONTAINS 80 OR 1418 00:55:58,400 --> 00:55:59,640 90 BILLION NEURONS. 1419 00:55:59,640 --> 00:56:01,720 AND SO YOU CAN BEGIN TO 1420 00:56:01,720 --> 00:56:03,160 APPRECIATE THE INCREDIBLE 1421 00:56:03,160 --> 00:56:04,600 COMPLEXITY, EVEN OF A MOUSE 1422 00:56:04,600 --> 00:56:06,680 BRAIN, WHEN YOU REALIZE THEY'RE 1423 00:56:06,680 --> 00:56:08,360 LOOKING AT A TINY FRACTION IN 1424 00:56:08,360 --> 00:56:10,680 EACH OF THESE IMAGES, A TINY 1425 00:56:10,680 --> 00:56:12,560 FRACTION OF THE TOTAL NUMBER OF 1426 00:56:12,560 --> 00:56:13,760 NEURONS IN THE BRAIN. 1427 00:56:13,760 --> 00:56:16,800 AND EACH ONE OF THESE NEURONS IS 1428 00:56:16,800 --> 00:56:17,960 SENDING INFORMATION TO THOUSANDS 1429 00:56:17,960 --> 00:56:20,000 OF TARGET NEURONS IN OTHER PARTS 1430 00:56:20,000 --> 00:56:22,000 OF THE BRAIN AND ALSO RECEIVING 1431 00:56:22,000 --> 00:56:23,720 INFORMATION SIMILARLY FROM 1432 00:56:23,720 --> 00:56:25,880 THOUSANDS OF OTHER NEURONS IN 1433 00:56:25,880 --> 00:56:26,720 DIFFERENT PARTS OF THE BRAIN. 1434 00:56:26,720 --> 00:56:29,640 THIS IS A PYRAMIDAL 1435 00:56:29,640 --> 00:56:31,240 NEURON OF THE HIPPOCAMPUS, AND 1436 00:56:31,240 --> 00:56:33,560 WE'RE MEASURING MEMBRANE 1437 00:56:33,560 --> 00:56:35,080 POTENTIAL, SO TRANSMEMBRANE 1438 00:56:35,080 --> 00:56:36,760 POTENTIAL WHICH NORMALLY HAS A 1439 00:56:36,760 --> 00:56:40,600 RESTING VALUE OF AROUND MINUS 7, 1440 00:56:40,600 --> 00:56:43,520 AND THEN THERE'S A THRESHOLD FOR 1441 00:56:43,520 --> 00:56:44,920 ACTION POTENTIAL GENERATION OF 1442 00:56:44,920 --> 00:56:46,560 ABOUT MINUS 50 MILLIVOLTS, AND 1443 00:56:46,560 --> 00:56:48,280 FOR REFERENCE, I PUT ANOTHER 1444 00:56:48,280 --> 00:56:50,560 LINE HERE AT ZERO MILL BOLTS. 1445 00:56:50,560 --> 00:56:53,000 SO NOW LET'S SUPPOSE THERE'S A 1446 00:56:53,000 --> 00:56:55,720 SINGLE SYNAPTIC INPUT INTO THE 1447 00:56:55,720 --> 00:56:56,640 DENDRITIC TREE OF THIS NEWER ON. 1448 00:56:56,640 --> 00:56:58,320 WHAT WILL HAPPEN IS A SMALL 1449 00:56:58,320 --> 00:56:59,640 DEPOLARIZATION OF THE MEMBRANE 1450 00:56:59,640 --> 00:57:01,080 POTENTIAL FROM ITS NORMAL 1451 00:57:01,080 --> 00:57:01,960 RESTING LEVEL TOWARDS THE 1452 00:57:01,960 --> 00:57:03,480 THRESHOLD. 1453 00:57:03,480 --> 00:57:05,800 THEN IF A SECOND -- WE CALL THIS 1454 00:57:05,800 --> 00:57:08,800 AN EPSP FOR EXCITATORY POST 1455 00:57:08,800 --> 00:57:09,240 SYNAPTIC POTENTIAL. 1456 00:57:09,240 --> 00:57:11,640 SO THE SECOND NEURON, SECOND 1457 00:57:11,640 --> 00:57:13,240 SYNAPSE IS ACTIVATED WITH A 1458 00:57:13,240 --> 00:57:13,760 BRIEF DELAY. 1459 00:57:13,760 --> 00:57:15,640 THIS INCREASES THE SIZE OF THE 1460 00:57:15,640 --> 00:57:16,280 RESPONSE. 1461 00:57:16,280 --> 00:57:17,360 THIRD NEURON WOULD INCREASE THE 1462 00:57:17,360 --> 00:57:20,360 SIZE OF THE RESPONSE EVEN 1463 00:57:20,360 --> 00:57:20,600 FURTHER. 1464 00:57:20,600 --> 00:57:21,560 AND A FOURTH NEURON WOULD 1465 00:57:21,560 --> 00:57:22,680 INCREASE THE SIZE OF THE 1466 00:57:22,680 --> 00:57:24,640 RESPONSE TO DRIVE THE MEMBRANE 1467 00:57:24,640 --> 00:57:26,560 POTENTIAL ABOVE THE THRESHOLD 1468 00:57:26,560 --> 00:57:29,040 FOR GENERATION OF AN ACTION 1469 00:57:29,040 --> 00:57:29,760 POTENTIAL. 1470 00:57:29,760 --> 00:57:32,040 NOW, I WANT TO POINT OUT SOME 1471 00:57:32,040 --> 00:57:34,920 REALLY GROSS OVERSIMPLIFICATIONS 1472 00:57:34,920 --> 00:57:35,640 HERE. 1473 00:57:35,640 --> 00:57:36,680 SO FIRST OF ALL, IN A NEURON 1474 00:57:36,680 --> 00:57:39,360 LIKE THIS, A PYRAMIDAL NEURON, 1475 00:57:39,360 --> 00:57:43,400 FOUR EXCITATORY SIN A SYNAPSES D 1476 00:57:43,400 --> 00:57:45,120 ALMOST CERTAINLY NOT BE ENOUGH 1477 00:57:45,120 --> 00:57:46,400 TO DRIVE POTENTIAL FIRING IN 1478 00:57:46,400 --> 00:57:46,920 THIS NEWER ON. 1479 00:57:46,920 --> 00:57:48,720 IT WOULD REQUIRE MORE LIKE 40 OR 1480 00:57:48,720 --> 00:57:51,480 MAYBE EVEN A HUNDRED SYNAPTIC 1481 00:57:51,480 --> 00:57:53,000 INPUTS, EXCITATORY SYNAPTIC 1482 00:57:53,000 --> 00:57:54,640 INPUTS TO PRODUCE AN ACTION 1483 00:57:54,640 --> 00:57:55,640 POTENTIAL. 1484 00:57:55,640 --> 00:57:56,720 NEVERTHELESS CONCEPTUALLY IT'S 1485 00:57:56,720 --> 00:57:57,880 THE SAME IDEA, YOU NEED 1486 00:57:57,880 --> 00:57:59,840 SUMMATION OF THE MEMBRANE 1487 00:57:59,840 --> 00:58:01,360 POTENTIAL CHANGES CAUSED BY EACH 1488 00:58:01,360 --> 00:58:03,080 INPUT IN ORDER TO REACH 1489 00:58:03,080 --> 00:58:04,600 THRESHOLD. 1490 00:58:04,600 --> 00:58:06,680 NOW, THIS LINE HERE THAT I ADDED 1491 00:58:06,680 --> 00:58:08,040 TO THE DIAGRAM IS INTENDED TO 1492 00:58:08,040 --> 00:58:10,560 DEPICT THE AXON, AND THE ACTION 1493 00:58:10,560 --> 00:58:11,800 POTENTIAL IS ACTUALLY GENERATED 1494 00:58:11,800 --> 00:58:14,760 IN THE AXON WHEN THE MEMBRANE 1495 00:58:14,760 --> 00:58:15,640 POTENTIAL HITS THRESHOLD, AND 1496 00:58:15,640 --> 00:58:17,800 THEN THE ACTION POTENTIAL 1497 00:58:17,800 --> 00:58:20,000 PROPAGATES ALONG THE AXON TOWARD 1498 00:58:20,000 --> 00:58:23,520 THE NERVE ENDINGS OF THE AXON 1499 00:58:23,520 --> 00:58:24,120 ARBORIZATION. 1500 00:58:24,120 --> 00:58:27,960 YOU SAW WHAT SOME OF THOSE AXON 1501 00:58:27,960 --> 00:58:28,960 ARBORIZATIONS LOOKED LIKE IN THE 1502 00:58:28,960 --> 00:58:30,520 MOVIE THAT I SHOWED YOU. 1503 00:58:30,520 --> 00:58:32,560 IF WE CONSIDER THEN ONE OTHER 1504 00:58:32,560 --> 00:58:34,280 IMPORTANT FEATURE HERE, WHICH IS 1505 00:58:34,280 --> 00:58:35,720 INHIBITION, SO IMAGINE WE HAVE A 1506 00:58:35,720 --> 00:58:37,080 SINGLE INHIBITORY INTERNEURON 1507 00:58:37,080 --> 00:58:38,800 HERE SHOWN IN RED, FORMING A 1508 00:58:38,800 --> 00:58:41,240 SYNAPSE ON THIS CELL, IF 1509 00:58:41,240 --> 00:58:43,640 ACTIVATED ON ITS OWN, IT WOULD 1510 00:58:43,640 --> 00:58:44,640 ACTUALLY HYPERPOLARIZE THE 1511 00:58:44,640 --> 00:58:47,280 MEMBRANE, THAT IS, MOVE IT AWAY 1512 00:58:47,280 --> 00:58:48,640 FROM THE RESTING POTENTIAL. 1513 00:58:48,640 --> 00:58:51,480 WE CALL THIS AN INHIBITORY POST 1514 00:58:51,480 --> 00:58:53,360 SYNAPTIC POTENTIAL OR IPSP, AND 1515 00:58:53,360 --> 00:58:55,000 IF THE INHIBITORY INPUT IS 1516 00:58:55,000 --> 00:58:56,680 ACTIVATED TOGETHER WITH THE 1517 00:58:56,680 --> 00:58:58,120 EXCITATORY INPUTS, THAT CAN BE 1518 00:58:58,120 --> 00:58:59,960 ENOUGH TO PREVENT THOSE 1519 00:58:59,960 --> 00:59:01,960 EXCITATORY INPUTS FROM REACHING 1520 00:59:01,960 --> 00:59:06,800 THRESHOLD AND DRIVING IN ACTION 1521 00:59:06,800 --> 00:59:07,400 POTENTIAL. 1522 00:59:07,400 --> 00:59:08,800 SO ONE OF THE KEY THINGS, EVERY 1523 00:59:08,800 --> 00:59:10,520 NEURON INTEGRATES SYNAPTIC INPUT 1524 00:59:10,520 --> 00:59:12,240 FROM BOTH EXCITATORY AND 1525 00:59:12,240 --> 00:59:13,760 INHIBITORY SYNAPTIC INPUTS, AND 1526 00:59:13,760 --> 00:59:15,640 AT ANY GIVEN MOMENT, WHETHER THE 1527 00:59:15,640 --> 00:59:17,320 CELL IS FIRING AN ACTION 1528 00:59:17,320 --> 00:59:20,160 POTENTIAL OR NOT IS DETERMINED 1529 00:59:20,160 --> 00:59:22,280 LARGELY BY WHETHER SYNAPTIC 1530 00:59:22,280 --> 00:59:24,280 INPUTS ARE SUFFICIENT TO DRIVE 1531 00:59:24,280 --> 00:59:26,160 THE MEMBRANE POTENTIAL IN THE 1532 00:59:26,160 --> 00:59:27,440 AXON TO THAT THRESHOLD FOR 1533 00:59:27,440 --> 00:59:27,760 FIRING. 1534 00:59:27,760 --> 00:59:29,360 NOW THERE ARE MANY, MANY OTHER 1535 00:59:29,360 --> 00:59:32,120 FACTORS THAT INFLUENCE THIS 1536 00:59:32,120 --> 00:59:33,240 INPUT/OUTPUT RELATIONSHIP, SO 1537 00:59:33,240 --> 00:59:35,520 FOR EXAMPLE, WE AND MANY OTHERS 1538 00:59:35,520 --> 00:59:38,400 HAVE SHOWN THAT THE DENDRITIC 1539 00:59:38,400 --> 00:59:40,320 TREES OF THESE NEURONS CONTAIN 1540 00:59:40,320 --> 00:59:42,800 MANY DIFFERENT TYPES OF ION 1541 00:59:42,800 --> 00:59:44,360 CHANNELS THAT CAN ALSO INFLUENCE 1542 00:59:44,360 --> 00:59:45,920 THE WAY SYNAPTIC INPUTS ARE 1543 00:59:45,920 --> 00:59:47,120 INTEGRATED BY THESE NEURONS. 1544 00:59:47,120 --> 00:59:48,480 THE STRUCTURE OF THE DENDRITIC 1545 00:59:48,480 --> 00:59:50,360 TREE IS ALSO AN IMPORTANT 1546 00:59:50,360 --> 00:59:52,640 FACTOR, AND AS I SHOWED YOU, 1547 00:59:52,640 --> 00:59:53,960 DENDRITIC STRUCTURE IS HIGHLY 1548 00:59:53,960 --> 00:59:54,800 VARIABLE ACROSS DIFFERENT 1549 00:59:54,800 --> 00:59:55,480 NEURONS AND DIFFERENT PARTS OF 1550 00:59:55,480 --> 00:59:57,080 THE BRAIN, AND EVEN WITHIN THE 1551 00:59:57,080 --> 00:59:58,280 SAME PART OF THE BRAIN, YOU CAN 1552 00:59:58,280 --> 01:00:00,200 FIND NEURONS WITH VARYING 1553 01:00:00,200 --> 01:00:01,400 DENDRITIC STRUCTURES. 1554 01:00:01,400 --> 01:00:03,360 SO WE BELIEVE THAT THE 1555 01:00:03,360 --> 01:00:05,320 COMPUTATION THAT IS PERFORMED, 1556 01:00:05,320 --> 01:00:07,280 THE INPUT/OUTPUT COMPUTATION 1557 01:00:07,280 --> 01:00:09,360 THAT'S PERFORMED BY EACH NEURON 1558 01:00:09,360 --> 01:00:11,040 DEPENDS ON THOSE FACTORS, THINGS 1559 01:00:11,040 --> 01:00:12,920 LIKE THE STRUCTURE OF THE 1560 01:00:12,920 --> 01:00:14,560 DENDRITES, PROPERTIES OF THE 1561 01:00:14,560 --> 01:00:15,800 SYNAPSES, THE TYPES OF SYNAPSES 1562 01:00:15,800 --> 01:00:17,160 THAT ARE ACTIVATED AND THE TYPES 1563 01:00:17,160 --> 01:00:20,000 OF LI LIGAND AND VOLTAGE GATED 1564 01:00:20,000 --> 01:00:21,280 CHANNELS IN THE MEMBRANE THAT 1565 01:00:21,280 --> 01:00:23,120 ARE ACTIVATED WHEN THESE 1566 01:00:23,120 --> 01:00:27,480 PROCESSES ARE OCCURRING. 1567 01:00:27,480 --> 01:00:29,320 SO WHAT HAPPENS WHEN THAT ACTION 1568 01:00:29,320 --> 01:00:30,480 POTENTIAL GETS TO THE END OF THE 1569 01:00:30,480 --> 01:00:32,040 AXON OR ALONG THE AXON, THERE 1570 01:00:32,040 --> 01:00:36,160 ARE THOUSANDS OF TERMINALS 1571 01:00:36,160 --> 01:00:37,560 CHEMICAL SYNAPTIC TRANSMISSION 1572 01:00:37,560 --> 01:00:38,640 IS OCCURRING WITH THE TARGET 1573 01:00:38,640 --> 01:00:39,080 NEURONS. 1574 01:00:39,080 --> 01:00:40,520 THIS IS KIND OF A FANCY PICTURE 1575 01:00:40,520 --> 01:00:42,440 I FOUND ON THE WEB THAT SHOWS 1576 01:00:42,440 --> 01:00:43,720 HOW CHEMICAL SYNAPTIC 1577 01:00:43,720 --> 01:00:44,160 TRANSMISSION WORKS. 1578 01:00:44,160 --> 01:00:46,360 YOU HAVE A PRESYNAPTIC TERMINAL 1579 01:00:46,360 --> 01:00:47,880 RELEASING MOLECULES ON TO THE 1580 01:00:47,880 --> 01:00:50,600 POST SYNAPTIC NEURON, AND THAT 1581 01:00:50,600 --> 01:00:53,560 CHEMICAL SYNAPTIC TRANSMISSION 1582 01:00:53,560 --> 01:00:56,040 TURNS AN ACTION POTENTIAL ON THE 1583 01:00:56,040 --> 01:00:59,840 PRESYNAPTIC SIDE INTO AN EPSP OR 1584 01:00:59,840 --> 01:01:01,280 IPSP LIKE THE ONES I JUST SHOWED 1585 01:01:01,280 --> 01:01:04,640 YOU ON THE POST SYNAPTIC SIDE. 1586 01:01:04,640 --> 01:01:06,600 FREQUENTLY, YOU CAN SEE NEURAL 1587 01:01:06,600 --> 01:01:08,600 CIRCUITS DEPICTED AS THESE VERY 1588 01:01:08,600 --> 01:01:10,520 SIMPLE DRAWINGS WHERE EXCITATORY 1589 01:01:10,520 --> 01:01:13,240 AND INHIBITORY SYNAPSES ARE 1590 01:01:13,240 --> 01:01:15,760 DEPICTED IN A CARTOON-LIKE 1591 01:01:15,760 --> 01:01:16,400 FASHION DESCRIBING SOME OF THE 1592 01:01:16,400 --> 01:01:17,960 CIRCUITRY THAT CAN BE FOUND IN 1593 01:01:17,960 --> 01:01:19,280 THE NERVOUS SYSTEM OF MANY 1594 01:01:19,280 --> 01:01:21,240 DIFFERENT TYPES OF ANIMALS, BUT 1595 01:01:21,240 --> 01:01:23,840 OBVIOUSLY WHAT WE WANT IS A MORE 1596 01:01:23,840 --> 01:01:25,720 SOPHISTICATED UNDERSTANDING OF 1597 01:01:25,720 --> 01:01:27,120 SYNAPSES AND CIRCUITS AND 1598 01:01:27,120 --> 01:01:29,640 NEURONS THAN IS REVEALED BY 1599 01:01:29,640 --> 01:01:33,560 SIMPLE DIAGRAMS LIKE THIS. 1600 01:01:33,560 --> 01:01:35,400 NOW ONE WAY OF THINKING ABOUT 1601 01:01:35,400 --> 01:01:37,880 WHAT OUR GOAL IS IN TERMS OF 1602 01:01:37,880 --> 01:01:41,520 UNDERSTANDING HOW THE BRAIN 1603 01:01:41,520 --> 01:01:43,360 WORKS IS TO THINK ABOUT 1604 01:01:43,360 --> 01:01:44,360 ARTIFICIAL NEURAL NETWORKS. 1605 01:01:44,360 --> 01:01:46,080 WE'RE ALL PROBABLY VERY FAMILIAR 1606 01:01:46,080 --> 01:01:47,800 WITH ARTIFICIAL NEURAL NETWORKS 1607 01:01:47,800 --> 01:01:49,680 THESE DAYS, READING THE NEWS 1608 01:01:49,680 --> 01:01:54,760 ABOUT CHAT GPT AND PLAY PLAIINGH 1609 01:01:54,760 --> 01:01:56,720 CHAT GPT OR WATCHING THE MOVIE 1610 01:01:56,720 --> 01:01:58,200 ALPHA GO, WHICH IF YOU HAVEN'T 1611 01:01:58,200 --> 01:02:00,080 SEEN IT I'D HIGHLY RECOMMEND IT. 1612 01:02:00,080 --> 01:02:02,040 IT'S A DESCRIPTION ABOUT HOW 10 1613 01:02:02,040 --> 01:02:03,680 YEARS AGO THE DEEP MIND TEAM WAS 1614 01:02:03,680 --> 01:02:06,040 ABLE TO DEVELOP AN ARTIFICIAL 1615 01:02:06,040 --> 01:02:08,560 NEURAL NETWORK THAT BEAT THE 1616 01:02:08,560 --> 01:02:09,680 BEST PLAYERS IN THE WORLD AT THE 1617 01:02:09,680 --> 01:02:10,320 GAME OF GO. 1618 01:02:10,320 --> 01:02:12,680 THIS IS ALL DONE WITH VERY, VERY 1619 01:02:12,680 --> 01:02:14,000 LARGE BUT -- YOU KNOW, AT THE 1620 01:02:14,000 --> 01:02:16,400 CORE, RELATIVELY SIMPLE NEURAL 1621 01:02:16,400 --> 01:02:19,040 NETWORK ARCHITECTURE. 1622 01:02:19,040 --> 01:02:20,840 SO THIS IS A PARTICULARLY SIMPLE 1623 01:02:20,840 --> 01:02:21,720 NEURAL NETWORK THAT'S DEPICTED 1624 01:02:21,720 --> 01:02:22,360 HERE. 1625 01:02:22,360 --> 01:02:25,560 THIS IS A FEED FORWARD NETWORK. 1626 01:02:25,560 --> 01:02:27,800 IT HAS AN INPUT LAYER, AN OUTPUT 1627 01:02:27,800 --> 01:02:29,200 LAYER, AND IN BETWEEN, A BUNCH 1628 01:02:29,200 --> 01:02:30,080 OF HIDDEN LAYERS. 1629 01:02:30,080 --> 01:02:32,880 AND MOST OF THESE ARTIFICIAL 1630 01:02:32,880 --> 01:02:34,440 UNUSUAL NETWORKS ARE, IN FACT, 1631 01:02:34,440 --> 01:02:35,440 INSPIRED BY THE PROPERTIES OF 1632 01:02:35,440 --> 01:02:36,200 REAL NEURAL NETWORKS. 1633 01:02:36,200 --> 01:02:37,440 FOR EXAMPLE, INDIVIDUAL 1634 01:02:37,440 --> 01:02:39,200 ELEMENTS, WE CAN THINK OF AS 1635 01:02:39,200 --> 01:02:40,040 NEURONS. 1636 01:02:40,040 --> 01:02:42,360 THE CONNECTIONS BETWEEN THEM AS 1637 01:02:42,360 --> 01:02:45,480 MEDIATED BY AXONS, AND SYNAPSES, 1638 01:02:45,480 --> 01:02:47,360 AND REALLY IMPORTANTLY, THESE 1639 01:02:47,360 --> 01:02:49,480 SYNAPSES HAVE ADJUSTABLE 1640 01:02:49,480 --> 01:02:49,720 WEIGHTS. 1641 01:02:49,720 --> 01:02:51,920 AND THE KEY TO LEARNING IN THESE 1642 01:02:51,920 --> 01:02:54,560 ARTIFICIAL SYSTEMS IS SIMPLY 1643 01:02:54,560 --> 01:02:56,000 ADJUSTING THE WEIGHTS OF EACH OF 1644 01:02:56,000 --> 01:02:58,320 THESE CONNECTIONS WITHIN THESE 1645 01:02:58,320 --> 01:03:02,480 SYSTEMS AND DOING THAT IN A WAY 1646 01:03:02,480 --> 01:03:07,160 THAT HELPS ACHIEVE THE TARGET. 1647 01:03:07,160 --> 01:03:08,680 ON THE INPUT LAYER YOU MIGHT 1648 01:03:08,680 --> 01:03:11,040 HAVE A PICTURE OF AN ANIMAL, ON 1649 01:03:11,040 --> 01:03:12,840 THE OUTPUT LAYER, THE 1650 01:03:12,840 --> 01:03:13,680 INFORMATION WOULD THEN GET 1651 01:03:13,680 --> 01:03:14,880 MATCHED TO A DOG OR CAT OR 1652 01:03:14,880 --> 01:03:16,640 WHATEVER KIND OF ANIMAL WAS BEST 1653 01:03:16,640 --> 01:03:18,320 MATCHED BY THE INPUT. 1654 01:03:18,320 --> 01:03:21,280 OKAY. 1655 01:03:21,280 --> 01:03:25,440 SO ONE WAY OF TRYING TO 1656 01:03:25,440 --> 01:03:26,520 UNDERSTAND ON BRAIN FUNCTION IS, 1657 01:03:26,520 --> 01:03:28,480 HOW DO REAL BRAINS DIFFER FROM 1658 01:03:28,480 --> 01:03:29,480 THESE ARTIFICIAL NEURAL 1659 01:03:29,480 --> 01:03:29,880 NETWORKS? 1660 01:03:29,880 --> 01:03:31,880 WE KNOW NOW THAT ARTIFICIAL 1661 01:03:31,880 --> 01:03:34,600 NEURAL NETWORKS CAN SURPASS THE 1662 01:03:34,600 --> 01:03:37,760 PERFORMANCE OF HUMANS IN MANY 1663 01:03:37,760 --> 01:03:39,280 NARROW DOMAINS OF INTEREST, FOR 1664 01:03:39,280 --> 01:03:41,240 EXAMPLE, PLAYING THE GAME OF GO, 1665 01:03:41,240 --> 01:03:42,320 BUT THEY TEND TO FAIL WHEN 1666 01:03:42,320 --> 01:03:44,040 PITTED AGAINST HUMANS ON THINGS 1667 01:03:44,040 --> 01:03:45,600 THAT REQUIRE MORE GENERAL 1668 01:03:45,600 --> 01:03:45,920 INTELLIGENCE. 1669 01:03:45,920 --> 01:03:50,040 SO WHAT IS IT ABOUT THE BRAIN 1670 01:03:50,040 --> 01:03:51,240 THAT MAKES GENERAL INTELLIGENCE 1671 01:03:51,240 --> 01:03:52,560 IN HUMANS AND OTHER ANIMALS 1672 01:03:52,560 --> 01:03:54,240 POSSIBLE THAT IS NOT YET 1673 01:03:54,240 --> 01:03:55,560 CAPTURED BY THESE RELATIVELY 1674 01:03:55,560 --> 01:04:00,040 SIMPLE AI SYSTEMS? 1675 01:04:00,040 --> 01:04:01,520 WELL, THIS WAY OF THINKING ABOUT 1676 01:04:01,520 --> 01:04:05,040 NEURAL NETWORKS AS CONNECTIONIST 1677 01:04:05,040 --> 01:04:08,000 ARCHITECTURE REDUCES THE 1678 01:04:08,000 --> 01:04:10,040 CONNECTIVITY OF THE BRAIN DOWN 1679 01:04:10,040 --> 01:04:14,280 TO SIMPLY A SERIES OF MI TRI MAI 1680 01:04:14,280 --> 01:04:16,240 SEES OR WEIGHTS THAT CONNECT 1681 01:04:16,240 --> 01:04:17,240 DIFFERENT NEURONS WITHIN THE 1682 01:04:17,240 --> 01:04:17,760 NEURAL NETWORK. 1683 01:04:17,760 --> 01:04:19,040 WHEN IN FACT, WE KNOW THAT -- 1684 01:04:19,040 --> 01:04:21,800 AND THEN THE FUNCTION THAT'S 1685 01:04:21,800 --> 01:04:23,000 PERFORMED BY EACH ONE OF THESE 1686 01:04:23,000 --> 01:04:25,280 NEURONS IS AN INPUT/OUTPUT 1687 01:04:25,280 --> 01:04:26,600 FUNCTION THAT LOOKS SOMETHING 1688 01:04:26,600 --> 01:04:27,240 LIKE THIS ONE. 1689 01:04:27,240 --> 01:04:28,880 THIS IS CALLED THE RECTIFIED 1690 01:04:28,880 --> 01:04:29,520 LINEAR UNIT. 1691 01:04:29,520 --> 01:04:31,800 IT MEANS IF THE INPUTS ARE BELOW 1692 01:04:31,800 --> 01:04:33,160 THRESHOLD, THE OUTPUT IS ZERO, 1693 01:04:33,160 --> 01:04:35,800 BUT IF THE INPUT IS ABOVE 1694 01:04:35,800 --> 01:04:37,440 THRESHOLD, THE OUTPUT IS 1695 01:04:37,440 --> 01:04:40,040 PROPORTIONAL TO THE SIZE OF THAT 1696 01:04:40,040 --> 01:04:40,920 ABOVE-THRESHOLD INPUT. 1697 01:04:40,920 --> 01:04:45,160 SO HOW IS IT THAT REAL NEURONS 1698 01:04:45,160 --> 01:04:47,520 SURPASS OR ALLOW US HUMANS AND 1699 01:04:47,520 --> 01:04:49,960 OTHER ANIMALS TO SURPASS THE 1700 01:04:49,960 --> 01:04:50,920 PERFORMANCE OF ARTIFICIAL 1701 01:04:50,920 --> 01:04:51,480 SYSTEMS? 1702 01:04:51,480 --> 01:04:52,640 WELL, WE KNOW, FOR INSTANCE, 1703 01:04:52,640 --> 01:04:54,320 THAT REAL BIOLOGY IS MUCH, MUCH 1704 01:04:54,320 --> 01:04:56,080 MORE COMPLICATED THAN THAT 1705 01:04:56,080 --> 01:04:58,520 SIMPLE PICTURE OF AN ARTIFICIAL 1706 01:04:58,520 --> 01:04:59,680 NEURAL NETWORK THAT I DESCRIBED. 1707 01:04:59,680 --> 01:05:01,640 FOR EXAMPLE, AT THE CHEMICAL 1708 01:05:01,640 --> 01:05:03,280 SYNAPSE, THERE ARE MOLECULAR 1709 01:05:03,280 --> 01:05:04,760 MACHINES ON BOTH THE PRE AND 1710 01:05:04,760 --> 01:05:06,320 POST SYNAPTIC SIDE THAT INVOLVE 1711 01:05:06,320 --> 01:05:08,600 HUNDREDS OF MOLECULES THAT 1712 01:05:08,600 --> 01:05:10,760 ORGANIZE STRAIGHT A REALLY 1713 01:05:10,760 --> 01:05:13,120 PRECISE PROCESS THAT ALLOWS, FOR 1714 01:05:13,120 --> 01:05:14,400 EXAMPLE, NEUROTRANSMITTERS TO BE 1715 01:05:14,400 --> 01:05:18,360 PACKAGED INTO VESICLES AND AXON 1716 01:05:18,360 --> 01:05:20,440 LOU TONS AND RESPONSE TO ACTION 1717 01:05:20,440 --> 01:05:22,080 POTENTIAL FIRING DEPICTED BY 1718 01:05:22,080 --> 01:05:24,240 THESE YELLOW FLASHES CAUSE THESE 1719 01:05:24,240 --> 01:05:25,240 NEUROTRANSMITTER CONTAINING 1720 01:05:25,240 --> 01:05:26,840 VESICLES TO FUSE WITH THE 1721 01:05:26,840 --> 01:05:28,360 PRESYNAPTIC MEMBRANE AND RELEASE 1722 01:05:28,360 --> 01:05:30,240 TRANSMITTER THAT THEN BINDS TO 1723 01:05:30,240 --> 01:05:32,000 ION CHANNELS ON THE POST 1724 01:05:32,000 --> 01:05:33,720 SYNAPTIC SIDE ALLOWING IONS TO 1725 01:05:33,720 --> 01:05:35,480 FLOW INTO THE POST SYNAPTIC CELL 1726 01:05:35,480 --> 01:05:38,320 AND PRODUCE EXCITATORY OR 1727 01:05:38,320 --> 01:05:39,320 INHIBITORY POST SYNAPTIC 1728 01:05:39,320 --> 01:05:39,640 POTENTIALS. 1729 01:05:39,640 --> 01:05:44,560 THEN THERE ARE ALSO GLIAL CELLS 1730 01:05:44,560 --> 01:05:46,160 THAT REGULATE THIS PROCESS IN 1731 01:05:46,160 --> 01:05:48,400 PART BY TAKING UP THE 1732 01:05:48,400 --> 01:05:49,440 NEUROTRANSMITTERS FROM THE 1733 01:05:49,440 --> 01:05:50,840 SYNAPTIC CLEFT AND DOING MANY 1734 01:05:50,840 --> 01:05:52,720 OTHER THINGS TO ENSURE THAT THIS 1735 01:05:52,720 --> 01:05:56,480 PROCESS OF SN SYNAPTIC TRANSMISN 1736 01:05:56,480 --> 01:05:59,440 IS ROBUST, FAST AND RELIABLE. 1737 01:05:59,440 --> 01:06:00,440 I'M GOING TO SHOW YOU THIS 1738 01:06:00,440 --> 01:06:02,200 MOVIE. 1739 01:06:02,200 --> 01:06:05,320 THIS COMES FROM A PUBLICATION 1740 01:06:05,320 --> 01:06:07,960 FROM HELM, ET AL., AND IT IS A 1741 01:06:07,960 --> 01:06:08,920 BEAUTIFUL STUDY THAT LOOKED AT 1742 01:06:08,920 --> 01:06:11,320 THE MOLECULAR COMPOSITION OF 1743 01:06:11,320 --> 01:06:13,840 THOUSANDS OF DENDRITIC SPINES, 1744 01:06:13,840 --> 01:06:16,360 AND THIS IS ONE DENDRITIC SPINE 1745 01:06:16,360 --> 01:06:18,000 THAT IS DEPICTED HERE, IS THE 1746 01:06:18,000 --> 01:06:20,600 POST SYNAPTIC SITE OF CONTACT ON 1747 01:06:20,600 --> 01:06:21,160 A DENDRITE. 1748 01:06:21,160 --> 01:06:23,560 THIS IS ABOUT A MICRON-LONG 1749 01:06:23,560 --> 01:06:24,960 STRUCTURE, AND INSIDE OF IT, 1750 01:06:24,960 --> 01:06:28,440 THERE ARE HUNDREDS OF PROTEINS, 1751 01:06:28,440 --> 01:06:29,880 POSSIBLY EVEN THOUSANDS OF 1752 01:06:29,880 --> 01:06:30,840 PROTEINS CONTRIBUTING TO THIS 1753 01:06:30,840 --> 01:06:31,840 PROCESS OF SYNAPTIC 1754 01:06:31,840 --> 01:06:32,160 TRANSMISSION. 1755 01:06:32,160 --> 01:06:33,680 AND THE MOVIE JUST KIND OF GOES 1756 01:06:33,680 --> 01:06:38,800 THROUGH AND SHOWS YOU BASED ON A 1757 01:06:38,800 --> 01:06:40,920 RECONSTRUCTION OF SINGLE SPINES 1758 01:06:40,920 --> 01:06:45,120 AND HUNDREDS OF MOLECULES HOW 1759 01:06:45,120 --> 01:06:46,320 INCREDIBLY COMPLEX THIS 1760 01:06:46,320 --> 01:06:47,960 STRUCTURE IS, JUST ONE SIDE OF 1761 01:06:47,960 --> 01:06:49,280 THE SYNAPSE, AND YOU'RE LOOKING 1762 01:06:49,280 --> 01:06:53,760 AT VARIOUS TYPES OF PROTEINS 1763 01:06:53,760 --> 01:06:54,960 DEPICTED INSIDE OF THE SYNAPSE. 1764 01:06:54,960 --> 01:06:57,040 AND ALL OF THIS MOLECULAR 1765 01:06:57,040 --> 01:06:58,440 MACHINERY ALLOWS THE CELL NOT 1766 01:06:58,440 --> 01:07:00,960 ONLY TO RESPOND TO THOSE 1767 01:07:00,960 --> 01:07:02,280 PRESYNAPTIC CHEMICALS THAT ARE 1768 01:07:02,280 --> 01:07:03,600 RELEASED ON TO THE POST SYNAPTIC 1769 01:07:03,600 --> 01:07:06,400 SPINE, BUT ALSO TO ENGAGE IN 1770 01:07:06,400 --> 01:07:07,400 BIOCHEMICAL REACTIONS THAT ALLOW 1771 01:07:07,400 --> 01:07:09,400 THE WEIGHT OF THAT SYNAPTIC 1772 01:07:09,400 --> 01:07:11,280 CONNECTION TO BE CHANGED AS A 1773 01:07:11,280 --> 01:07:12,280 FUNCTION OF EXPERIENCE. 1774 01:07:12,280 --> 01:07:14,360 AND THIS CONCEPT OF CHANGING 1775 01:07:14,360 --> 01:07:16,240 SYNAPTIC WEIGHTS IS A FUNCTION 1776 01:07:16,240 --> 01:07:19,040 OF EXPERIENCE IS BELIEVED TO BE 1777 01:07:19,040 --> 01:07:20,960 REALLY CENTRAL TO THE CONCEPT OF 1778 01:07:20,960 --> 01:07:22,320 LEARNING AND HOW MEMORIES ARE 1779 01:07:22,320 --> 01:07:22,560 FORMED. 1780 01:07:22,560 --> 01:07:26,960 SO WE CAN THINK ABOUT MEMORIES 1781 01:07:26,960 --> 01:07:27,840 ESSENTIALLY AS CHANGES IN THE 1782 01:07:27,840 --> 01:07:30,120 WEIGHTS OF SYNAPSES THAT ALTER 1783 01:07:30,120 --> 01:07:33,200 ACTIVITY IN THE BRAIN AND ALLOW 1784 01:07:33,200 --> 01:07:35,440 THE BRAIN TO RESPOND TO INCOMING 1785 01:07:35,440 --> 01:07:37,840 SENSORY INFORMATION AND INTERNAL 1786 01:07:37,840 --> 01:07:39,680 INFORMATION COMING FROM OUR 1787 01:07:39,680 --> 01:07:42,760 BODIES TO PRODUCE UNIQUE TYPES 1788 01:07:42,760 --> 01:07:46,160 OF CONSCIOUS EXPERIENCES WHEN 1789 01:07:46,160 --> 01:07:48,800 THOSE THINGS HAPPEN. 1790 01:07:48,800 --> 01:07:50,080 SO AGAIN, THE GOAL IS TO 1791 01:07:50,080 --> 01:07:52,720 UNDERSTAND HOW THE BRAIN WORKS, 1792 01:07:52,720 --> 01:07:55,560 WHICH MEANS UNDERSTANDING HOW 1793 01:07:55,560 --> 01:07:56,600 PROTEINS, WHICH WE CAN MEASURE 1794 01:07:56,600 --> 01:07:58,560 ON THE SCALE OF NANOMETERS, AND 1795 01:07:58,560 --> 01:07:59,640 ORGANELLES AND CELLS WHICH ARE 1796 01:07:59,640 --> 01:08:02,160 MEASURED ON THE SCALE OF 1797 01:08:02,160 --> 01:08:03,240 MICRONS, INFLUENCE THE FUNCTION 1798 01:08:03,240 --> 01:08:05,200 OF ORGANS, LIKE BRAINS ON THE 1799 01:08:05,200 --> 01:08:07,120 SCALE OF MILLIMETERS AND EVEN IN 1800 01:08:07,120 --> 01:08:09,240 WHOLE ANIMALS ON THE SCALE OF 1801 01:08:09,240 --> 01:08:14,440 COUNCILMEM --OF CENTIMETERS AND. 1802 01:08:14,440 --> 01:08:16,520 SO THIS IS THE GOAL OF MANY 1803 01:08:16,520 --> 01:08:17,840 STUDYING THE FUND MENTAL BIOLOGY 1804 01:08:17,840 --> 01:08:18,880 OF THE NERVOUS SYSTEM AND IT'S 1805 01:08:18,880 --> 01:08:20,000 HARD, IT REQUIRES THAT MANY 1806 01:08:20,000 --> 01:08:21,880 PEOPLE DO STUDIES AT THESE 1807 01:08:21,880 --> 01:08:23,920 DIFFERENT LEVELS AND TRY TO 1808 01:08:23,920 --> 01:08:26,440 UNDERSTAND MECHANISTIC 1809 01:08:26,440 --> 01:08:27,200 RELATIONSHIPS BETWEEN THESE 1810 01:08:27,200 --> 01:08:28,280 DIFFERENT LEVELS OF 1811 01:08:28,280 --> 01:08:29,480 UNDERSTANDING HOW THE NERVOUS 1812 01:08:29,480 --> 01:08:30,120 SYSTEM FUNCTIONS. 1813 01:08:30,120 --> 01:08:33,760 AND I THINK THIS IS REALLY THE 1814 01:08:33,760 --> 01:08:36,000 ANSWER TO THE QUESTION HOW THE 1815 01:08:36,000 --> 01:08:38,320 BRAIN WORKS WILL REALLY BE 1816 01:08:38,320 --> 01:08:40,440 ANSWERS TO MANY, MANY QUESTIONS 1817 01:08:40,440 --> 01:08:42,920 ABOUT THE FUNCTIONAL 1818 01:08:42,920 --> 01:08:43,880 RELATIONSHIPS BETWEEN THESE 1819 01:08:43,880 --> 01:08:46,640 DIFFERENT STRUCTURES THAT WE 1820 01:08:46,640 --> 01:08:48,720 STUDY AT DIFFERENT LEVELS -- 1821 01:08:48,720 --> 01:08:50,000 SIZE LEVELS AND ORGANIZATIONAL 1822 01:08:50,000 --> 01:08:51,640 LEVELS IN NERVOUS SYSTEMS. 1823 01:08:51,640 --> 01:08:53,800 TO GIVE YOU AN APPRECIATION FOR 1824 01:08:53,800 --> 01:08:55,960 THAT, I'M GOING TO SHOW YOU 1825 01:08:55,960 --> 01:08:56,920 ANOTHER MOVIE. 1826 01:08:56,920 --> 01:08:59,720 THIS IS PROVIDED GENEROUSLY BY 1827 01:08:59,720 --> 01:09:01,960 JEFF LICTHMAN FROM HARVARD 1828 01:09:01,960 --> 01:09:02,280 UNIVERSITY. 1829 01:09:02,280 --> 01:09:04,240 HE AND HIS GROUP OBTAINED FROM A 1830 01:09:04,240 --> 01:09:07,520 PATIENT WHO HAD TISSUE RESECTED 1831 01:09:07,520 --> 01:09:09,680 FOR EPILEPSY SOME OF THE 1832 01:09:09,680 --> 01:09:11,120 UNDAMAGED TISSUE THAT HAD TO BE 1833 01:09:11,120 --> 01:09:13,680 REMOVED ALONG WITH THE EPILEPTIC 1834 01:09:13,680 --> 01:09:14,160 SEIZURE FOCUS. 1835 01:09:14,160 --> 01:09:17,520 THIS IS FROM THE NEOCORTEX, WAS 1836 01:09:17,520 --> 01:09:20,360 THEN PRESERVED AN IMAGE USING 1837 01:09:20,360 --> 01:09:21,560 SERIAL ELECTRON MICROSCOPY, AND 1838 01:09:21,560 --> 01:09:23,200 THEN IN COLLABORATION WITH 1839 01:09:23,200 --> 01:09:25,280 GOOGLE, THEIR TEAM RECONSTRUCTED 1840 01:09:25,280 --> 01:09:26,800 EVERY SINGLE STRUCTURE INSIDE 1841 01:09:26,800 --> 01:09:29,120 THIS RELATIVELY LARGE PIECE OF 1842 01:09:29,120 --> 01:09:30,640 HUMAN CORTEX. 1843 01:09:30,640 --> 01:09:35,560 AND THE MOVIE SORT OF ZOOMS IN 1844 01:09:35,560 --> 01:09:38,160 TO THE EXTREMELY HIGH RESOLUTION 1845 01:09:38,160 --> 01:09:39,600 VIEW PROVIDED BY THE ELECTRON 1846 01:09:39,600 --> 01:09:39,920 MICROSCOPE. 1847 01:09:39,920 --> 01:09:42,640 AND IN THESE HIGH RESOLUTION 1848 01:09:42,640 --> 01:09:43,960 VIEW, YOU CAN SEE THINGS LIKE 1849 01:09:43,960 --> 01:09:46,680 CELL BODY, DENDRITES, AXONS AND 1850 01:09:46,680 --> 01:09:48,280 SYNAPSES, AND EVERY SINGLE ONE 1851 01:09:48,280 --> 01:09:49,400 OF THOSE STRUCTURES IN THIS 1852 01:09:49,400 --> 01:09:51,600 VOLUME HAS BEEN RECONSTRUCTED 1853 01:09:51,600 --> 01:09:52,680 FOR FURTHER ANALYSIS. 1854 01:09:52,680 --> 01:09:55,720 AND THIS IS ONE OF THE GREAT 1855 01:09:55,720 --> 01:09:59,040 CHALLENGES, IS TO IMAGE LARGE 1856 01:09:59,040 --> 01:10:00,280 VOLUMES OF TISSUE AT HIGH 1857 01:10:00,280 --> 01:10:00,600 RESOLUTION. 1858 01:10:00,600 --> 01:10:02,840 I SHOWED YOU ONE EXAMPLE OF THAT 1859 01:10:02,840 --> 01:10:06,960 IN THAT MOVIE FROM THE 1860 01:10:06,960 --> 01:10:09,720 MOUSELIGHT TEAM HERE AT JANELIA. 1861 01:10:09,720 --> 01:10:11,240 THIS IS ANOTHER EXAMPLE OF USING 1862 01:10:11,240 --> 01:10:13,000 VERY HIGH RESOLUTION FORM OF 1863 01:10:13,000 --> 01:10:14,320 MICROSCOPY TO STUDY LARGE 1864 01:10:14,320 --> 01:10:16,160 VOLUMES OF TISSUE. 1865 01:10:16,160 --> 01:10:18,000 IT INVOLVES NOT ONLY THE 1866 01:10:18,000 --> 01:10:19,320 TECHNOLOGY OF THE MICROSCOPY, 1867 01:10:19,320 --> 01:10:22,160 BUT ALSO THE COMPUTATIONAL 1868 01:10:22,160 --> 01:10:23,040 TECHNOLOGY REQUIRED TO STITCH 1869 01:10:23,040 --> 01:10:25,880 ALL THESE IMAGES TOGETHER AND 1870 01:10:25,880 --> 01:10:27,520 THEN RECONSTRUCT THOUSANDS OF 1871 01:10:27,520 --> 01:10:29,280 NEURONS AND TENS OR HUNDREDS OF 1872 01:10:29,280 --> 01:10:31,120 THOUSANDS OF SYNAPTIC 1873 01:10:31,120 --> 01:10:32,000 CONNECTIONS BETWEEN THESE 1874 01:10:32,000 --> 01:10:32,960 NEURONS. 1875 01:10:32,960 --> 01:10:35,600 AND THIS HAS BEEN DONE, FOR 1876 01:10:35,600 --> 01:10:40,840 EXAMPLE, HERE AT JANELIA FOR THE 1877 01:10:40,840 --> 01:10:42,560 DROSOPHILA FRUIT FLY BRAIN, AND 1878 01:10:42,560 --> 01:10:44,080 THE TEAM IS WELL ON THEIR WAY OF 1879 01:10:44,080 --> 01:10:46,960 HAVING THE ENTIRE FRUIT FLY 1880 01:10:46,960 --> 01:10:48,360 BRAIN IMAGED AND THEN 1881 01:10:48,360 --> 01:10:49,560 RECONSTRUCTED SO THAT EVERY 1882 01:10:49,560 --> 01:10:51,320 SINGLE NEURON AND EVERY SINGLE 1883 01:10:51,320 --> 01:10:52,480 CONNECTION BETWEEN ALL THOSE 1884 01:10:52,480 --> 01:10:54,800 NEURONS CAN BE DESCRIBED IN 1885 01:10:54,800 --> 01:10:55,640 DETAIL. 1886 01:10:55,640 --> 01:10:58,600 THIS HAS PROVEN TO BE REALLY 1887 01:10:58,600 --> 01:10:59,600 INCREDIBLY ENABLING FOR THE 1888 01:10:59,600 --> 01:11:01,960 PEOPLE WHO ARE STUDYING THE 1889 01:11:01,960 --> 01:11:03,280 RELATIONSHIP BETWEEN NEURONS AND 1890 01:11:03,280 --> 01:11:08,520 THE FUNCTION OF THE ANIMAL. 1891 01:11:08,520 --> 01:11:12,160 NOW COMING BACK TO JEFF LICHTMAN 1892 01:11:12,160 --> 01:11:13,680 AND HIS TEAM'S WORK AT HARVARD, 1893 01:11:13,680 --> 01:11:14,880 HERE'S FROM THAT VOLUME THAT I 1894 01:11:14,880 --> 01:11:21,000 JUST SHOWED YOU SINGLE PYRAMIDAL 1895 01:11:21,000 --> 01:11:24,800 CELL SHOWN IN BLUE, YOU CAN SEE 1896 01:11:24,800 --> 01:11:25,880 THE DENDRITIC SPINES. 1897 01:11:25,880 --> 01:11:27,720 THESE ARE PROTRUSIONS FROM THE 1898 01:11:27,720 --> 01:11:28,960 DENDRITES THAT ARE THE POST 1899 01:11:28,960 --> 01:11:31,120 SYNAPTIC SITES OF CONTACT OF 1900 01:11:31,120 --> 01:11:32,000 PRESYNAPTIC AXONS. 1901 01:11:32,000 --> 01:11:33,600 SO THE PRESYNAPTIC AXONS ARE NOT 1902 01:11:33,600 --> 01:11:35,120 SHOWN HERE, BUT EACH ONE OF 1903 01:11:35,120 --> 01:11:36,480 THOSE DENDRITIC SPINES WOULD 1904 01:11:36,480 --> 01:11:39,280 RECEIVE SYNAPTIC INPUT FROM THE 1905 01:11:39,280 --> 01:11:42,560 PRESYNAPTIC AXON OF ANOTHER 1906 01:11:42,560 --> 01:11:47,160 NEURON. 1907 01:11:47,160 --> 01:11:52,400 HERE'S ANOTHER DEPICTION, YOU 1908 01:11:52,400 --> 01:11:55,800 CAN GET AN APPRECIATION FOR HOW 1909 01:11:55,800 --> 01:11:58,200 INCREDIBLY COMPLICATED THE 1910 01:11:58,200 --> 01:12:00,400 CONNECTIVITY OF THE NERVOUS 1911 01:12:00,400 --> 01:12:02,000 SYSTEM IS BY LOOKING AT THESE 1912 01:12:02,000 --> 01:12:03,440 BEAUTIFUL IMAGES. 1913 01:12:03,440 --> 01:12:05,800 AND ZOOMING IN TO EVEN HIGHER 1914 01:12:05,800 --> 01:12:07,400 RESOLUTION, ON THE LEFT YOU CAN 1915 01:12:07,400 --> 01:12:10,040 SEE A SINGLE SMALL PIECE OF THIS 1916 01:12:10,040 --> 01:12:11,280 LARGE VOLUME ELECTRON 1917 01:12:11,280 --> 01:12:13,240 MICROSCOPY, YOU CAN SEE THE 1918 01:12:13,240 --> 01:12:15,240 PRESYNAPTIC TERMINAL HIGHLIGHTED 1919 01:12:15,240 --> 01:12:18,040 HERE IN BLUE, THE POST SYNAPTIC 1920 01:12:18,040 --> 01:12:19,520 DENDRITE AND DENDRITIC SPINE. 1921 01:12:19,520 --> 01:12:20,960 THE MAGENTA, YOU CAN EVEN SEE 1922 01:12:20,960 --> 01:12:24,120 THE VESICLES AND THE PRESYNAPTIC 1923 01:12:24,120 --> 01:12:24,360 TERMINAL. 1924 01:12:24,360 --> 01:12:26,400 THOSE ARE THE NEUROTRANSMITTER 1925 01:12:26,400 --> 01:12:27,800 CONTAINING VESICLES THAT WOULD 1926 01:12:27,800 --> 01:12:29,080 RELEASE CHEMICAL TRANSMITTERS ON 1927 01:12:29,080 --> 01:12:31,880 TO THE POST SYNAPTIC DENDRITE 1928 01:12:31,880 --> 01:12:33,800 AND PRODUCE A RESPONSE IN THE 1929 01:12:33,800 --> 01:12:35,560 POST SYNAPTIC NEURON. 1930 01:12:35,560 --> 01:12:36,880 AGAIN, SINCE EACH OF THESE 1931 01:12:36,880 --> 01:12:38,400 NEURONS IS RECEIVING THOUSANDS 1932 01:12:38,400 --> 01:12:40,040 OF THESE SYNAPTIC INPUTS, MANY 1933 01:12:40,040 --> 01:12:42,760 OF THEM HAVE TO BE ACTIVATED IN 1934 01:12:42,760 --> 01:12:44,080 CLOSE TEMPORAL PROXIMITY IN 1935 01:12:44,080 --> 01:12:45,800 ORDER FOR THE CELL TO GENERATE A 1936 01:12:45,800 --> 01:12:47,920 RESPONSE. 1937 01:12:47,920 --> 01:12:50,960 AND LICHTMAN WITH HIS TEAM ALONG 1938 01:12:50,960 --> 01:12:52,600 WITH MANY OTHER PEOPLE USING 1939 01:12:52,600 --> 01:12:53,480 COMPLEMENTARY APPROACHES ARE 1940 01:12:53,480 --> 01:12:55,200 TRYING TO USE THIS VERY, VERY 1941 01:12:55,200 --> 01:12:56,520 DETAILED STRUCTURAL INFORMATION 1942 01:12:56,520 --> 01:12:58,160 TO GAIN A BETTER UNDERSTANDING 1943 01:12:58,160 --> 01:13:00,360 OF HOW THE CONNECTIVITY OF THE 1944 01:13:00,360 --> 01:13:01,480 NERVOUS SYSTEM WILL INFLUENCE 1945 01:13:01,480 --> 01:13:03,600 ITS FUNCTION. 1946 01:13:03,600 --> 01:13:06,560 NOW ULTIMATELY, AGAIN, WE WANT 1947 01:13:06,560 --> 01:13:09,200 TO GO FROM THESE HIGH RESOLUTION 1948 01:13:09,200 --> 01:13:11,360 VIEWS OF CELLS AND SUBCELLULAR 1949 01:13:11,360 --> 01:13:12,640 ORGANS AND EVEN PROTEINS INTO 1950 01:13:12,640 --> 01:13:14,440 HOW THE NERVOUS SYSTEM GUIDES 1951 01:13:14,440 --> 01:13:19,320 THE FUNCTION OF ENTIRE ANIMALS. 1952 01:13:19,320 --> 01:13:20,440 AND TO DO THAT, MANY GROUPS ARE 1953 01:13:20,440 --> 01:13:22,920 NOW DOING THESE KINDS OF STUDIES 1954 01:13:22,920 --> 01:13:25,120 IN VIVO, IN BEHAVING ANIMALS. 1955 01:13:25,120 --> 01:13:26,720 MY GROUP IS WORKING AS MANY 1956 01:13:26,720 --> 01:13:29,920 PEOPLE ARE WITH MICE, AND USING 1957 01:13:29,920 --> 01:13:32,760 MICROSCOPY TO STUDY THE ACTIVITY 1958 01:13:32,760 --> 01:13:34,160 OF THESE -- OF NEURONS IN THE 1959 01:13:34,160 --> 01:13:35,400 BRAIN AT THE CELLULAR LEVEL 1960 01:13:35,400 --> 01:13:37,120 WHILE WE CHALLENGE THE ANIMALS 1961 01:13:37,120 --> 01:13:39,320 TO LEARN TO DO TASKS IN A 1962 01:13:39,320 --> 01:13:42,280 VIRTUAL REALITY ENVIRONMENT. 1963 01:13:42,280 --> 01:13:45,560 SO ANIMAL IS SITTING ON A LARGE 1964 01:13:45,560 --> 01:13:47,000 SPHERICAL STYROFOAM BALL WHICH 1965 01:13:47,000 --> 01:13:49,040 IS FLOATING ON A CUSHION OF AIR. 1966 01:13:49,040 --> 01:13:50,880 THE ANIMALS ARE HEAD-FIX SOD WE 1967 01:13:50,880 --> 01:13:53,400 CAN USE A MICROSCOPE TO IMAGE 1968 01:13:53,400 --> 01:13:56,560 ACTIVITY IN THE BRAIN, AND I 1969 01:13:56,560 --> 01:13:58,320 THINK -- IT CHANGES THE VIEW ON 1970 01:13:58,320 --> 01:13:59,920 THESE SCREENS AROUND THEM TO 1971 01:13:59,920 --> 01:14:01,240 PRODUCE THE ILLUSION OF 1972 01:14:01,240 --> 01:14:02,760 NAVIGATING IN VIRTUAL REALITY. 1973 01:14:02,760 --> 01:14:04,880 THIS IS WHAT IT LOOKS LIKE 1974 01:14:04,880 --> 01:14:06,160 PHOTOGRAPHICALLY. 1975 01:14:06,160 --> 01:14:07,920 HERE'S THIS LARGE SPHERICAL 1976 01:14:07,920 --> 01:14:09,200 TREADMILL, HERE'S THE MOUSE, AND 1977 01:14:09,200 --> 01:14:11,320 HERE'S THIS OBJECTIVE FROM THIS 1978 01:14:11,320 --> 01:14:12,400 MICROSCOPE THAT WAS DESIGNED AND 1979 01:14:12,400 --> 01:14:14,360 BUILT HERE AT JANELIA, AND IT 1980 01:14:14,360 --> 01:14:16,320 ALLOWS US TO IMAGE THE ACTIVITY 1981 01:14:16,320 --> 01:14:18,440 OF INDIVIDUAL NEURONS, THOUSANDS 1982 01:14:18,440 --> 01:14:20,160 OF INDIVIDUAL NEURONS IN THE 1983 01:14:20,160 --> 01:14:22,000 HIPPOCAMPUS, WHILE THE ANIMAL IS 1984 01:14:22,000 --> 01:14:23,320 RUBBING AND LEARNING AND 1985 01:14:23,320 --> 01:14:24,280 PERFORMING A TASK. 1986 01:14:24,280 --> 01:14:27,560 AND WE CAN NOW IMAGE 5 TO 10,000 1987 01:14:27,560 --> 01:14:29,120 HIPPO CAM PAL NEURONS EVERY DAY 1988 01:14:29,120 --> 01:14:31,200 FOR WEEKS AS WE TRAIN ANIMALS TO 1989 01:14:31,200 --> 01:14:34,280 DO TASKS, AND THAT'S GIVING US 1990 01:14:34,280 --> 01:14:36,240 SOME INSIGHT INTO HOW NEURAL 1991 01:14:36,240 --> 01:14:39,160 ACTIVITY CHANGES AS THE ANIMAL 1992 01:14:39,160 --> 01:14:42,280 LESHES LEARNS AND FORMS MEMORIE. 1993 01:14:42,280 --> 01:14:43,840 THIS IS ONLY POSSIBLE BECAUSE 1994 01:14:43,840 --> 01:14:49,040 EACH IS EXPRESSING A PROTEIN 1995 01:14:49,040 --> 01:14:51,560 CALLED GKAMP THAT IS SENSITIVE 1996 01:14:51,560 --> 01:14:52,120 TO CALCIUM. 1997 01:14:52,120 --> 01:14:53,640 SO EACH TIME AN ACTION POTENTIAL 1998 01:14:53,640 --> 01:14:55,640 FIRES IN THESE NEURONS, CALCIUM 1999 01:14:55,640 --> 01:14:57,480 ENTERS THE CELL AND CAUSES AN 2000 01:14:57,480 --> 01:15:00,560 INCREASE IN FLUORESCENCE 2001 01:15:00,560 --> 01:15:01,680 SUBMITTED BY THE MOLECULES 2002 01:15:01,680 --> 01:15:02,960 EXPRESSED IN THESE NEURONS, AND 2003 01:15:02,960 --> 01:15:05,280 THAT'S A CELLULAR RESOLUTION 2004 01:15:05,280 --> 01:15:06,800 MEASUREMENT OF NEURAL ACTIVITY 2005 01:15:06,800 --> 01:15:08,440 IN THESE ANIMALS. 2006 01:15:08,440 --> 01:15:10,400 AND AGAIN, BY DOING THIS EVERY 2007 01:15:10,400 --> 01:15:12,520 DAY AND ALIGNING THE DATA FROM 2008 01:15:12,520 --> 01:15:14,680 ACROSS DAYS AND WATCHING HOW 2009 01:15:14,680 --> 01:15:16,560 THINGS CHANGE AS THE ANIMAL 2010 01:15:16,560 --> 01:15:18,600 LEARNS, IT GIVES US SOME INSIGHT 2011 01:15:18,600 --> 01:15:21,360 INTO HOW MEMORIES ARE FORMED AND 2012 01:15:21,360 --> 01:15:22,480 HOW THEY'RE STORED IN THE 2013 01:15:22,480 --> 01:15:22,800 HIPPOCAMPUS. 2014 01:15:22,800 --> 01:15:24,680 SO ANOTHER WAY OF MEASURING 2015 01:15:24,680 --> 01:15:27,920 NEURAL ACTIVITY IN BEHAVING 2016 01:15:27,920 --> 01:15:30,880 ANIMALS IS TO USE ELECTRODES, 2017 01:15:30,880 --> 01:15:32,640 AND AT JANELIA, WE RECENTLY 2018 01:15:32,640 --> 01:15:35,920 DEVELOPED A NEW TYPE OF PROBES 2019 01:15:35,920 --> 01:15:37,320 CALLED NEUROPIXEL PROBES, AND 2020 01:15:37,320 --> 01:15:39,520 THESE ARE HIGH SITE COUNT PROBES 2021 01:15:39,520 --> 01:15:44,360 THAT ARE FABRICATED AT A 2022 01:15:44,360 --> 01:15:45,640 NANOFABRICATION FACILITY IN 2023 01:15:45,640 --> 01:15:46,640 BELGIUM, PROBABLY THE ONLY 2024 01:15:46,640 --> 01:15:47,600 FACILITY IN THE WORLD THAT CAN 2025 01:15:47,600 --> 01:15:51,640 BUILD THESE STATE OF THE ART 2026 01:15:51,640 --> 01:15:53,080 PROBES BECAUSE IT'S A RESEARCH 2027 01:15:53,080 --> 01:15:54,480 FACILITY AS OPPOSED TO A 2028 01:15:54,480 --> 01:15:55,160 COMMERCIAL FACILITY OR IN 2029 01:15:55,160 --> 01:15:57,760 ADDITION TO BEING A COMMERCIAL 2030 01:15:57,760 --> 01:15:58,080 FACILITY. 2031 01:15:58,080 --> 01:16:00,040 AND THESE PROBES NOW ARE REALLY 2032 01:16:00,040 --> 01:16:01,600 IMPROVING THE WAY THAT 2033 01:16:01,600 --> 01:16:02,600 NEUROSCIENTISTS CAN MEASURE 2034 01:16:02,600 --> 01:16:06,480 NEURAL ACTIVITY IN THE BRAINS OF 2035 01:16:06,480 --> 01:16:07,480 BEHAVING ANIMALS, WHETHER THAT 2036 01:16:07,480 --> 01:16:11,240 BE MICE OR RATS OR NON-HUMAN 2037 01:16:11,240 --> 01:16:12,720 PRIMATES, AND THE NEURAL 2038 01:16:12,720 --> 01:16:14,520 ACTIVITY THAT CAN BE MEASURED IN 2039 01:16:14,520 --> 01:16:16,560 MANY DIFFERENT BRAIN REGIONS 2040 01:16:16,560 --> 01:16:17,760 SIMULTANEOUSLY FROM HUNDREDS OR 2041 01:16:17,760 --> 01:16:19,760 EVEN THOUSANDS OF NEURONS, 2042 01:16:19,760 --> 01:16:21,600 AGAIN, AS ANIMALS ARE PERFORMING 2043 01:16:21,600 --> 01:16:26,520 INTERESTING TASKS. 2044 01:16:26,520 --> 01:16:27,920 ANOTHER REALLY IMPORTANT 2045 01:16:27,920 --> 01:16:29,680 APPROACH THAT HAS REVOLUTIONIZED 2046 01:16:29,680 --> 01:16:34,400 THE FIELD IS CALLED 2047 01:16:34,400 --> 01:16:35,280 TRANSCRIPTOMICS, THE ABILITY TO 2048 01:16:35,280 --> 01:16:36,680 DETERMINE WHICH GENES ARE 2049 01:16:36,680 --> 01:16:38,320 EXPRESSED IN INDIVIDUAL CELLS. 2050 01:16:38,320 --> 01:16:39,520 THIS IMAGE YOU'RE LOOKING AT ON 2051 01:16:39,520 --> 01:16:41,360 THE LEFT IS FROM A RECENT 2052 01:16:41,360 --> 01:16:46,320 PUBLICATION WHERE A SINGLE CELL 2053 01:16:46,320 --> 01:16:48,480 ANALYSIS WAS DONE FOR ABOUT 2054 01:16:48,480 --> 01:16:49,240 1.7 MILLION NEURONS IN THE MOUSE 2055 01:16:49,240 --> 01:16:49,480 BRAIN. 2056 01:16:49,480 --> 01:16:50,920 OVER ON THE RIGHT SIDE, YOU CAN 2057 01:16:50,920 --> 01:16:53,200 SEE CLASSIFICATION OF THOSE 2058 01:16:53,200 --> 01:16:54,760 NEURONS INTO DIFFERENT TYPES, 2059 01:16:54,760 --> 01:16:57,920 AND IT TURNS OUT THAT THE 2060 01:16:57,920 --> 01:17:00,520 DIVERSITY OF NEURONS IN THE 2061 01:17:00,520 --> 01:17:01,960 MOUSE BRAIN IS MUCH, MUCH 2062 01:17:01,960 --> 01:17:03,480 GREATER THAN WE HAD EVER BEFORE 2063 01:17:03,480 --> 01:17:04,920 APPRECIATED JUST BY LOOKING AT 2064 01:17:04,920 --> 01:17:05,240 MORPHOLOGIES. 2065 01:17:05,240 --> 01:17:08,440 WHEN YOU START LOOKING AT GENE 2066 01:17:08,440 --> 01:17:09,840 EXPRESSION ACROSS THE BRAIN, YOU 2067 01:17:09,840 --> 01:17:11,360 SEE THAT THERE ARE MANY, MANY 2068 01:17:11,360 --> 01:17:12,360 DIFFERENT TYPES OF CELLS IN 2069 01:17:12,360 --> 01:17:15,120 TERMS OF THE COMPLEMENT OF GENES 2070 01:17:15,120 --> 01:17:16,520 THAT THEY EXPRESS AND EVEN IF 2071 01:17:16,520 --> 01:17:20,000 YOU ZOOM IN ON ONE PARTICULAR 2072 01:17:20,000 --> 01:17:23,600 BRAIN REGION OR THE CA1 THAT MY 2073 01:17:23,600 --> 01:17:25,920 LAB STUDIES EXTENSIVELY, YOU SEE 2074 01:17:25,920 --> 01:17:27,640 THAT CELLS THAT WE USED TO THINK 2075 01:17:27,640 --> 01:17:30,280 OF AS A MONOLITHIC POPULATION OF 2076 01:17:30,280 --> 01:17:31,800 NEURONS ACTUALLY CAN CONSIST OF 2077 01:17:31,800 --> 01:17:34,080 MANY DIFFERENT TYPES THAT DIFFER 2078 01:17:34,080 --> 01:17:36,840 VERY SUBTLELY IN TERMS OF GENE 2079 01:17:36,840 --> 01:17:38,560 EXPRESSION, AND THEN WHEN YOU 2080 01:17:38,560 --> 01:17:40,880 LOOK, YOU FIND THAT STRUCTURAL 2081 01:17:40,880 --> 01:17:41,760 AND FUNCTIONAL DIFFERENCES 2082 01:17:41,760 --> 01:17:42,640 CORRELATE WITH THOSE DIFFERENCES 2083 01:17:42,640 --> 01:17:44,360 IN GENE EXPRESSION AS WELL. 2084 01:17:44,360 --> 01:17:46,040 SO ONE OF THE GREAT CHALLENGES 2085 01:17:46,040 --> 01:17:47,240 FOR NEUROSCIENCE GOING FORWARD 2086 01:17:47,240 --> 01:17:52,040 IS TO DETERMINE ESSENTIALLY AN 2087 01:17:52,040 --> 01:17:54,560 ATLAS OF THE CELL TYPES THAT ARE 2088 01:17:54,560 --> 01:17:55,880 FOUND IN THE BRAINS OF DIFFERENT 2089 01:17:55,880 --> 01:17:57,160 TYPES OF ANIMALS, AND THEN 2090 01:17:57,160 --> 01:17:59,160 TRYING TO RELATE THE ATLAS OF 2091 01:17:59,160 --> 01:18:04,400 CELL TYPES TO FUNCTION. 2092 01:18:04,400 --> 01:18:06,480 NOW, TRANSCRIPTOMICS GIVES YOU 2093 01:18:06,480 --> 01:18:07,800 OWL CRUDE RESOLUTION IN TERMS OF 2094 01:18:07,800 --> 01:18:08,840 SPATIAL LOCATION OF THE 2095 01:18:08,840 --> 01:18:10,640 DIFFERENT TYPES OF NEURONS 2096 01:18:10,640 --> 01:18:12,720 BECAUSE THEY'RE USUALLY SMALL 2097 01:18:12,720 --> 01:18:14,880 PARTS OF THE BRAIN ARE DISSECTED 2098 01:18:14,880 --> 01:18:17,640 AND THEN THE CELLS ARE 2099 01:18:17,640 --> 01:18:18,840 DISASSOCIATED AND GENE 2100 01:18:18,840 --> 01:18:19,680 EXPRESSION IS DETERMINED, BUT 2101 01:18:19,680 --> 01:18:21,440 THE LEVEL OF RESOLUTION ABOUT 2102 01:18:21,440 --> 01:18:23,120 WHERE THOSE CELLS CAME FROM, 2103 01:18:23,120 --> 01:18:26,360 WHERE THEY'RE LOCATED IN THE 2104 01:18:26,360 --> 01:18:27,720 BRAIN IS LIMITED TO HOW SMALL 2105 01:18:27,720 --> 01:18:30,320 PIECES OF TISSUE CAN BE 2106 01:18:30,320 --> 01:18:30,880 DISSECTED OUT. 2107 01:18:30,880 --> 01:18:34,160 SO THERE'S A BIG, BIG PUSH IN 2108 01:18:34,160 --> 01:18:36,560 THE FIELD TO DO WHAT'S CALLED 2109 01:18:36,560 --> 01:18:37,240 SPATIAL TRANSCRIPTOMIC, WHICH 2110 01:18:37,240 --> 01:18:39,120 IS -- AND THIS IS FROM ANOTHER 2111 01:18:39,120 --> 01:18:41,840 RECENT PAPER THAT APPEARED AS A 2112 01:18:41,840 --> 01:18:42,920 PRE-PRINT LAST MONTH. 2113 01:18:42,920 --> 01:18:48,200 AGAIN SHOWING -- THIS IS A 2114 01:18:48,200 --> 01:18:49,280 REPRESENTATION OF ALL THE GENES 2115 01:18:49,280 --> 01:18:50,560 EXPRESSED IN HUNDREDS OF 2116 01:18:50,560 --> 01:18:52,440 THOUSANDS OF CELLS, AND THEN A 2117 01:18:52,440 --> 01:18:53,760 VARIETY OF METHODS HAVE BEEN 2118 01:18:53,760 --> 01:18:55,600 DEVELOPED THAT ALLOW THE 2119 01:18:55,600 --> 01:18:57,040 COLLECTION OF GENES THAT 2120 01:18:57,040 --> 01:18:58,120 DESCRIBE THESE DIFFERENT TYPES 2121 01:18:58,120 --> 01:19:01,120 OF CELLS TO BE MAPPED ON TO 2122 01:19:01,120 --> 01:19:02,640 THEIR LOCATION IN THE MOUSE 2123 01:19:02,640 --> 01:19:04,280 BRAIN. 2124 01:19:04,280 --> 01:19:07,320 AND THIS IS -- REALLY THIS 2125 01:19:07,320 --> 01:19:09,000 APPROACH, SPATIAL 2126 01:19:09,000 --> 01:19:11,800 TRANSCRIPTOMICS, COMBINED WITH 2127 01:19:11,800 --> 01:19:18,400 SISINGLE CELL -- IT'S A REVOLUTN 2128 01:19:18,400 --> 01:19:19,480 THAT'S LIKELY TO BE EXTENDED 2129 01:19:19,480 --> 01:19:21,480 INTO MANY OTHER TYPES OF 2130 01:19:21,480 --> 01:19:24,520 ANIMALS, INCLUDING HUMANS AS WE 2131 01:19:24,520 --> 01:19:27,400 NOW SEE MORE AND MORE PEOPLE 2132 01:19:27,400 --> 01:19:30,240 DOING TRANSCRIPTOMICS AND 2133 01:19:30,240 --> 01:19:32,720 SPATIAL TRANSCRIPTOMICS ON HUMAN 2134 01:19:32,720 --> 01:19:33,920 AS WELL AS MOUSE TISSUE. 2135 01:19:33,920 --> 01:19:39,320 SO FINALLY, WHAT DO WE DO THIS 2136 01:19:39,320 --> 01:19:41,200 WITH INFORMATION, ONCE WE HAVE 2137 01:19:41,200 --> 01:19:42,920 THIS ATLAS OF CELL TYPES? 2138 01:19:42,920 --> 01:19:47,200 ONE OF THE THINGS WE CAN DO IS 2139 01:19:47,200 --> 01:19:51,800 I -- THERE ARE VARIOUS FORMS 2140 01:19:51,800 --> 01:19:53,200 THAT HAVE BEEN ENGINEERED TO 2141 01:19:53,200 --> 01:19:54,960 ALLOW US TO STIM LAY NEURON, SO 2142 01:19:54,960 --> 01:19:57,120 INSTEAD OF USING A MORE 2143 01:19:57,120 --> 01:19:59,760 TRADITIONAL APPROACH OF USING 2144 01:19:59,760 --> 01:20:02,080 LEK TRAL STIMULATION WHICH WOULD 2145 01:20:02,080 --> 01:20:03,480 STIMULATE ANY NEURON IN THE 2146 01:20:03,480 --> 01:20:05,920 VICINITY OF THE ELECTRICAL 2147 01:20:05,920 --> 01:20:08,320 STIMULATING ELECTRODE, TO 2148 01:20:08,320 --> 01:20:10,720 EXPRESS TRANSGENICICALLY THESE 2149 01:20:10,720 --> 01:20:12,360 LIGHT SENSITIVE PROTEINS THAT 2150 01:20:12,360 --> 01:20:15,840 HAVE BEEN EXCITED -- WHEN AN 2151 01:20:15,840 --> 01:20:17,200 APPROPRIATE WAVELENGTH OF LIGHT 2152 01:20:17,200 --> 01:20:18,400 IS SHOWN ON TO THEM. 2153 01:20:18,400 --> 01:20:20,560 SO THE IDEA IS YOU CAN TAKE 2154 01:20:20,560 --> 01:20:22,760 ADVANTAGE OF OUR KNOWLEDGE OF 2155 01:20:22,760 --> 01:20:25,480 GENE EXPRESSION TO EXPRESS THESE 2156 01:20:25,480 --> 01:20:27,560 TRANS GENES IN A SINGLE CELL 2157 01:20:27,560 --> 01:20:29,800 TYPE, AND THEN EITHER ACTIVATE 2158 01:20:29,800 --> 01:20:33,360 OR INHIBIT THAT CELL TYPE USING 2159 01:20:33,360 --> 01:20:35,400 LIGHT, AS ANIMALS ARE PERFORMING 2160 01:20:35,400 --> 01:20:35,760 TASKS. 2161 01:20:35,760 --> 01:20:38,160 YOU CAN DO THIS IN INTACT 2162 01:20:38,160 --> 01:20:38,760 BEHAVING ANIMALS. 2163 01:20:38,760 --> 01:20:40,520 OVER THE PAST DECADE OR MORE, A 2164 01:20:40,520 --> 01:20:42,440 LARGE NUMBER OF STUDIES HAVE 2165 01:20:42,440 --> 01:20:45,760 BEGUN TO USE OPTOGENETICS TO 2166 01:20:45,760 --> 01:20:46,600 EXPLORE THE FUNCTION OF 2167 01:20:46,600 --> 01:20:48,040 DIFFERENT TYPES OF NEURONS AND 2168 01:20:48,040 --> 01:20:50,640 DIFFERENT TYPES OF -- AND 2169 01:20:50,640 --> 01:20:51,800 DIFFERENT PARTS OF THE BRAIN AND 2170 01:20:51,800 --> 01:20:53,080 LOOK NOT ONLY AT HOW THAT 2171 01:20:53,080 --> 01:20:54,280 AFFECTS THE BEHAVIOR OF THE 2172 01:20:54,280 --> 01:20:56,920 ANIMAL, BUT HOW IT AFFECTS THE 2173 01:20:56,920 --> 01:21:00,520 ACTIVITY OF NEURONS THROUGHOUT 2174 01:21:00,520 --> 01:21:03,160 THE BRAIN. 2175 01:21:03,160 --> 01:21:04,480 SO WITH THAT, I THINK I'LL STOP 2176 01:21:04,480 --> 01:21:06,080 AND TRY TO LEAVE SOME TIME FOR 2177 01:21:06,080 --> 01:21:07,200 DISCUSSION. 2178 01:21:07,200 --> 01:21:10,120 I HOPE THAT WHIRLWIND TOUR OF 2179 01:21:10,120 --> 01:21:13,120 THE BRAIN HAS GIVEN YOU SOME 2180 01:21:13,120 --> 01:21:16,040 INSIGHT INTO HOW MODERN 2181 01:21:16,040 --> 01:21:18,000 NEUROSCIENCE IS DEVELOPING SOME 2182 01:21:18,000 --> 01:21:19,680 INCREDIBLE NEW TECHNIQUES AND 2183 01:21:19,680 --> 01:21:20,440 MAKING PROGRESS TOWARDS 2184 01:21:20,440 --> 01:21:21,960 ACHIEVING A BETTER UNDERSTANDING 2185 01:21:21,960 --> 01:21:24,000 OF THE FUNDAMENTAL PHYSIOLOGY OF 2186 01:21:24,000 --> 01:21:27,200 THE BRAIN AND HOW IT ENABLES THE 2187 01:21:27,200 --> 01:21:30,680 AMAZING THINGS THAT WE AND OTHER 2188 01:21:30,680 --> 01:21:32,040 ANIMALS CAN DO. 2189 01:21:32,040 --> 01:21:33,040 THANK YOU. 2190 01:21:33,040 --> 01:21:36,320 >>WELL, I WANT TO THANK YOU 2191 01:21:36,320 --> 01:21:41,360 BOTH FOR AN INCREDIBLY EXCITING 2192 01:21:41,360 --> 01:21:46,160 INSIGHTS INTO AREAS THAT MOST OF 2193 01:21:46,160 --> 01:21:47,800 US KNEW VERY LITTLE ABOUT, BUT 2194 01:21:47,800 --> 01:21:53,520 VERY SUPERFICIALLY, PERHAPS. 2195 01:21:53,520 --> 01:21:57,080 WE HAVE A WHOLE SERIES OF 2196 01:21:57,080 --> 01:21:59,600 QUESTIONS. 2197 01:21:59,600 --> 01:22:01,200 SOME OF THEM HAVE TO DO MORE 2198 01:22:01,200 --> 01:22:02,400 SPECIFICALLY WITH THE 2199 01:22:02,400 --> 01:22:05,640 HIPPOCAMPUS, AND WITH YOUR WORK, 2200 01:22:05,640 --> 01:22:08,720 NELSON, IN REGARD TO DIFFERENT 2201 01:22:08,720 --> 01:22:10,920 FORMS OF MEMORY AND SO FORTH. 2202 01:22:10,920 --> 01:22:14,400 SO EVEN THOUGH YOU DIDN'T DWELL 2203 01:22:14,400 --> 01:22:18,560 ON YOUR PARTICULAR RESEARCH OR 2204 01:22:18,560 --> 01:22:20,880 ON THE HIPPOCAMPUS IN 2205 01:22:20,880 --> 01:22:23,160 PARTICULAR, PERHAPS WE COULD 2206 01:22:23,160 --> 01:22:26,240 CONSIDER SOME OF THOSE QUESTIONS 2207 01:22:26,240 --> 01:22:30,240 BECAUSE PEOPLE KNEW ENOUGH TO 2208 01:22:30,240 --> 01:22:35,240 ASK ABOUT IT. 2209 01:22:35,240 --> 01:22:36,520 LET ME GIVE YOU A FEW OF THEM 2210 01:22:36,520 --> 01:22:38,880 AND SEE HOW YOU FEEL, AND MAYBE 2211 01:22:38,880 --> 01:22:39,800 MARCUS WOULD FEEL THEY WOULD 2212 01:22:39,800 --> 01:22:42,320 WANT TO RESPOND TO THEM. 2213 01:22:42,320 --> 01:22:42,880 OKAY. 2214 01:22:42,880 --> 01:22:47,320 SO ONE IS, WHAT HAS IMAGING 2215 01:22:47,320 --> 01:22:49,320 REVEALED ABOUT UNCONSCIOUS 2216 01:22:49,320 --> 01:22:52,160 LEARNING AND UNCONSCIOUS 2217 01:22:52,160 --> 01:22:52,920 MEMORIES? 2218 01:22:52,920 --> 01:22:55,240 AND I SUPPOSE WE COULD ADD ON TO 2219 01:22:55,240 --> 01:22:58,880 THAT, SLEEP. 2220 01:22:58,880 --> 01:23:02,800 SO MAYBE -- MARCUS, DO YOU WANT 2221 01:23:02,800 --> 01:23:03,840 TO COMMENT ABOUT THAT FROM THE 2222 01:23:03,840 --> 01:23:09,120 STANDPOINT OF IMAGING? 2223 01:23:09,120 --> 01:23:15,480 >>THERE'S ONE THAT CAME FROM 2224 01:23:15,480 --> 01:23:16,440 DAVID -- SEVERAL THINGS COME TO 2225 01:23:16,440 --> 01:23:19,840 MIND BUT ONE WAS HOW MUCH 2226 01:23:19,840 --> 01:23:21,720 INFORMATION COMES FROM THE 2227 01:23:21,720 --> 01:23:23,600 OUTSIDE WORLD FOR US TO PROCESS 2228 01:23:23,600 --> 01:23:25,320 IN THE FIRST PLACE? 2229 01:23:25,320 --> 01:23:28,560 SO YOU CAN FIGURE THAT THE 2230 01:23:28,560 --> 01:23:35,160 RETINA RECEIVES A FAIR AMOUNT OF 2231 01:23:35,160 --> 01:23:36,680 INFORMATION ALL THE TIME, AND 2232 01:23:36,680 --> 01:23:37,600 THE QUESTION IS FIRST OFF, HOW 2233 01:23:37,600 --> 01:23:39,120 MUCH OF THAT ACTUALLY GETS TO 2234 01:23:39,120 --> 01:23:46,000 THE VISUAL CORTEX? 2235 01:23:46,000 --> 01:23:47,520 IT'S ORDERS OF MAGNITUDE, LIKE 2236 01:23:47,520 --> 01:23:54,400 SIX ORDERS OF MAG TEUT LESS THAS 2237 01:23:54,400 --> 01:23:55,200 THAN THE INFORMATION THAT GETS 2238 01:23:55,200 --> 01:23:56,600 TO THE RETINA IN THE FIRST 2239 01:23:56,600 --> 01:23:57,080 PLACE. 2240 01:23:57,080 --> 01:23:58,480 SO YOU HAVE TO IMAGINE WITH OUR 2241 01:23:58,480 --> 01:23:59,520 ELEGANT VIEW OF THE WORLD AS WE 2242 01:23:59,520 --> 01:24:02,640 SEE IT, THAT THE BRAIN MUST BE 2243 01:24:02,640 --> 01:24:07,560 FILLING IN A LOT, BASED ON 2244 01:24:07,560 --> 01:24:08,520 EXPERIENCE, VARIOUS PEOPLE HAVE 2245 01:24:08,520 --> 01:24:11,720 TALKED ABOUT THIS, VERNON AND 2246 01:24:11,720 --> 01:24:13,800 OTHERS, BUT I THINK WE TEND TO 2247 01:24:13,800 --> 01:24:15,640 OVERLOOK THIS ENORMOUS AMOUNT OF 2248 01:24:15,640 --> 01:24:18,840 WHAT HAS TO BE A LARGE AMOUNT OF 2249 01:24:18,840 --> 01:24:23,080 NON-CONSCIOUS ACTIVITY BECAUSE 2250 01:24:23,080 --> 01:24:24,400 THE BANDWIDTH OF CONSCIOUSNESS 2251 01:24:24,400 --> 01:24:25,840 IS ACTUALLY NOT AS BIG AS YOU 2252 01:24:25,840 --> 01:24:27,040 MIGHT IMAGINE. 2253 01:24:27,040 --> 01:24:28,280 WHICH LEAVES FOR THE NERVOUS 2254 01:24:28,280 --> 01:24:29,920 SYSTEM A MAJOR ROLE OF 2255 01:24:29,920 --> 01:24:31,640 CONSTRUCTING OUR CONCEPT OF THE 2256 01:24:31,640 --> 01:24:33,160 WORLD AROUND US. 2257 01:24:33,160 --> 01:24:34,960 SO THAT WHEN WE, FOR EXAMPLE, 2258 01:24:34,960 --> 01:24:36,800 DECIDE TO GO BUY A CAR, AND WE 2259 01:24:36,800 --> 01:24:42,600 BUY THE RED CAR, YOU'D SAY, 2260 01:24:42,600 --> 01:24:44,880 WELL, WHY DEPARTMENT YOU B -- WY 2261 01:24:44,880 --> 01:24:46,560 DIDN'T YOU BUY THE RED FORD 2262 01:24:46,560 --> 01:24:48,040 INSTEAD OF THE BLUE CHEVROLET? 2263 01:24:48,040 --> 01:24:49,080 PEOPLE CAN COME UP WITH ALL 2264 01:24:49,080 --> 01:24:50,720 SORTS OF EXPLANATIONS BUT MY 2265 01:24:50,720 --> 01:24:53,120 GUESS WOULD BE THERE'S CERTAIN 2266 01:24:53,120 --> 01:24:54,440 INTUITIVE PROPERTIES OF THE 2267 01:24:54,440 --> 01:24:56,400 BRAIN THAT BIAS OUR JUDGMENTS, 2268 01:24:56,400 --> 01:24:58,920 AND MOST OF THAT IS 2269 01:24:58,920 --> 01:25:00,200 NON-CONSCIOUS. 2270 01:25:00,200 --> 01:25:01,640 JUST OUT OF THE PRACTICAL 2271 01:25:01,640 --> 01:25:04,120 NECESSITY OF IT BEING SO. 2272 01:25:04,120 --> 01:25:07,120 SO JUST A SMALL PART OF THIS, 2273 01:25:07,120 --> 01:25:14,760 BUT MY GUESS WOULD BE BUT 2274 01:25:14,760 --> 01:25:16,760 DAVID'S WORK -- IT WAS SO 2275 01:25:16,760 --> 01:25:18,200 ASTONISHING, THE BANDWIDTH OF 2276 01:25:18,200 --> 01:25:19,560 THE ACTUAL CONSCIOUSNESS IS NOT 2277 01:25:19,560 --> 01:25:21,240 VERY LARGE, RELATIVE TO THE 2278 01:25:21,240 --> 01:25:22,240 OVERALL COMPLEXITY OF THE 2279 01:25:22,240 --> 01:25:28,360 SYSTEM. 2280 01:25:28,360 --> 01:25:29,880 SO JUST A PASSING THOUGHT THAT 2281 01:25:29,880 --> 01:25:30,480 OCCURRED TO ME. 2282 01:25:30,480 --> 01:25:32,960 >>THAT'S INTERESTING. 2283 01:25:32,960 --> 01:25:34,560 SO NELSON, DO YOU WANT TO 2284 01:25:34,560 --> 01:25:35,480 COMMENT ABOUT THIS? 2285 01:25:35,480 --> 01:25:36,920 I SUPPOSE ONE OF THE QUESTIONS 2286 01:25:36,920 --> 01:25:40,360 THAT CAME UP WHEN YOU SHOWED THE 2287 01:25:40,360 --> 01:25:45,160 MOUSE STUDIES, HAVE YOU OR YOUR 2288 01:25:45,160 --> 01:25:46,360 COLLEAGUES OR OTHERS IN THE 2289 01:25:46,360 --> 01:25:50,760 FIELD USED SUCH AN EXPERIMENTAL 2290 01:25:50,760 --> 01:25:53,040 MODEL TO OBSERVE EFFECTS IN THE 2291 01:25:53,040 --> 01:25:55,800 PARAMETERS THAT YOU MENTIONED 2292 01:25:55,800 --> 01:25:59,400 WITH REGARD TO SLEEP OR 2293 01:25:59,400 --> 01:26:05,320 ANESTHESIA IN THE ANIMAL? 2294 01:26:05,320 --> 01:26:06,880 >>LET ME COMMENT ON THAT IN A 2295 01:26:06,880 --> 01:26:07,840 FEW DIFFERENT WAYS. 2296 01:26:07,840 --> 01:26:09,480 FIRST I WOULD SAY THE KIND OF 2297 01:26:09,480 --> 01:26:10,560 IMAGE STUDIES THAT I SHOWED YOU 2298 01:26:10,560 --> 01:26:12,000 ARE REALLY STILL IN THEIR 2299 01:26:12,000 --> 01:26:13,320 INFANCY AT THE MOMENT. 2300 01:26:13,320 --> 01:26:14,880 BUT ONE OF THE BIG ADVANTAGES IS 2301 01:26:14,880 --> 01:26:16,400 THE LARGE NUMBER OF NEURONS THAT 2302 01:26:16,400 --> 01:26:18,280 WE CAN RECORD FROM AND OUR 2303 01:26:18,280 --> 01:26:20,680 ABILITY TO GO BACK AND ASSESS 2304 01:26:20,680 --> 01:26:22,680 THE SAME NEURONS EVERY SINGLE 2305 01:26:22,680 --> 01:26:27,000 DAY. 2306 01:26:27,000 --> 01:26:28,800 BUT THIS WAS BUILDING ON A HUGE 2307 01:26:28,800 --> 01:26:30,560 BODY OF WORK OVER THE PAST 2308 01:26:30,560 --> 01:26:31,960 SEVERAL DECADES DONE BY A NUMBER 2309 01:26:31,960 --> 01:26:34,400 OF LABS WHO, INSTEAD OF USING 2310 01:26:34,400 --> 01:26:36,280 IMAGING, HAVE USED ELECTRODES 2311 01:26:36,280 --> 01:26:37,840 AND PLANTED IN THE BRAINS OF 2312 01:26:37,840 --> 01:26:39,280 MICE AND RATS, MOSTLY RATS 2313 01:26:39,280 --> 01:26:46,200 ACTUALLY HISTORICALLY, THAT HAVE 2314 01:26:46,200 --> 01:26:47,640 REVEALED A LOT ABOUT WHAT THE 2315 01:26:47,640 --> 01:26:49,080 HIPPOCAMPUS IS DOING NOT ONLY IN 2316 01:26:49,080 --> 01:26:50,720 THE WAKE ANIMAL BUT ALSO DURING 2317 01:26:50,720 --> 01:26:52,360 SLEEP. 2318 01:26:52,360 --> 01:26:54,560 SO TO TRY TO SUMMARIZE THE 2319 01:26:54,560 --> 01:26:57,800 EMERGING VIEW OF WHAT HAS COME 2320 01:26:57,800 --> 01:26:59,680 OUT OF THAT VERY LARGE BODY OF 2321 01:26:59,680 --> 01:27:01,440 WORK FROM SEVERAL LABORATORIES 2322 01:27:01,440 --> 01:27:06,480 ACROSS DECADES, THE BASIC IDEA 2323 01:27:06,480 --> 01:27:08,680 IS THAT THE HIPPOCAMPUS IS 2324 01:27:08,680 --> 01:27:09,760 INTERPRETING THE SENSORY 2325 01:27:09,760 --> 01:27:12,200 INFORMATION THAT'S COMING IN IN 2326 01:27:12,200 --> 01:27:14,040 THE CONTEXT OF WHAT THE ARN MALL 2327 01:27:14,040 --> 01:27:18,120 ANIMALIS DOING AND WHERE THE ANS 2328 01:27:18,120 --> 01:27:18,880 LOCATED. 2329 01:27:18,880 --> 01:27:20,320 SO THE EARLIEST VIEW OF WHAT THE 2330 01:27:20,320 --> 01:27:22,160 HIPPOCAMPUS WAS DOING IS IT WAS 2331 01:27:22,160 --> 01:27:24,000 PRODUCING A COGNITIVE MAP OF OUR 2332 01:27:24,000 --> 01:27:25,560 ENVIRONMENT, SO LITERALLY 2333 01:27:25,560 --> 01:27:27,760 MAPPING OUT THE PHYSICAL SPACES 2334 01:27:27,760 --> 01:27:32,600 THAT WE EXPLORE IN, AND THAT 2335 01:27:32,600 --> 01:27:33,880 IDEA HAS REALLY SURVIVED THE 2336 01:27:33,880 --> 01:27:35,000 TEST OF TIME. 2337 01:27:35,000 --> 01:27:37,640 MANY OF THE CELLS IN THE 2338 01:27:37,640 --> 01:27:38,400 HIPPOCAMPUS RESPOND BEST WHEN 2339 01:27:38,400 --> 01:27:40,680 THE ANIMAL IS IN A SPECIFIC 2340 01:27:40,680 --> 01:27:42,560 PLACE IN THE ENVIRONMENT. 2341 01:27:42,560 --> 01:27:45,440 IN ADDITION, THOUGH, A NEW IDEA, 2342 01:27:45,440 --> 01:27:49,360 A NEWER IDEA, STILL NOT THAT 2343 01:27:49,360 --> 01:27:50,920 NEW, CLOSE TO A COUPLE DECADES 2344 01:27:50,920 --> 01:27:53,400 OLD AT THIS POINT, IS THE IDEA 2345 01:27:53,400 --> 01:27:55,720 THAT CELLS WILL -- IN 2346 01:27:55,720 --> 01:27:56,640 HIPPOCAMPUS WILL RESPOND NOT 2347 01:27:56,640 --> 01:27:58,560 ONLY WHEN THE ANIMAL IS IN A 2348 01:27:58,560 --> 01:28:03,120 POSITION BUT ALSO IN CONTACT, SO 2349 01:28:03,120 --> 01:28:04,400 FOR EXAMPLE, IF IT'S MOVING IN A 2350 01:28:04,400 --> 01:28:05,600 CERTAIN DIRECTION OR IN IT'S 2351 01:28:05,600 --> 01:28:08,440 COMI --IF IT'S COMING FROM PLACO 2352 01:28:08,440 --> 01:28:10,400 PLACE B, THE CELL WILL RESPOND, 2353 01:28:10,400 --> 01:28:11,440 WHEREAS IF IT'S COMING FROM 2354 01:28:11,440 --> 01:28:12,840 PLACE C TO PLACE B, THE CELL 2355 01:28:12,840 --> 01:28:16,680 WILL NOT RESPOND IN LOCATION B. 2356 01:28:16,680 --> 01:28:18,520 SO THERE'S A LOT OF WORK THAT IS 2357 01:28:18,520 --> 01:28:20,280 SUGGESTING THAT THERE'S THIS 2358 01:28:20,280 --> 01:28:22,600 COGNITIVE MAP NOT ONLY OF THE 2359 01:28:22,600 --> 01:28:24,720 ENVIRONMENT BUT ALSO OF THE 2360 01:28:24,720 --> 01:28:25,720 ANIMAL'S BEHAVIOR AND THE 2361 01:28:25,720 --> 01:28:26,800 CONTEXT WITHIN WHICH THE ANIMAL 2362 01:28:26,800 --> 01:28:33,080 IS EXPERIENCING THAT ENVIRON 2363 01:28:33,080 --> 01:28:35,440 ENVIRONMENT. 2364 01:28:35,440 --> 01:28:36,920 THAT DOES NOT EXIST WHEN THE 2365 01:28:36,920 --> 01:28:37,600 ANIMAL IS BORN. 2366 01:28:37,600 --> 01:28:38,880 THE HIPPOCAMPUS IS BUILT TO 2367 01:28:38,880 --> 01:28:41,240 ALLOW THE FLEXIBILITY TO ALLOW 2368 01:28:41,240 --> 01:28:42,440 AN ANIMAL TO BUILD THOSE 2369 01:28:42,440 --> 01:28:43,640 COGNITIVE MAPS IN ANY KIND OF 2370 01:28:43,640 --> 01:28:45,480 ENVIRONMENT, NO MATTER WHAT IT 2371 01:28:45,480 --> 01:28:47,000 HAPPENS TO ENCOUNTER IN THE 2372 01:28:47,000 --> 01:28:47,440 COURSE OF THE SLIDE. 2373 01:28:47,440 --> 01:28:51,960 SO OBVIOUSLY THERE ARE SERB 2374 01:28:51,960 --> 01:28:57,320 THARE CERTAINTHINGS THAT ARE WIR 2375 01:28:57,320 --> 01:28:58,200 DEVELOPMENT AND WHAT WE WOULD 2376 01:28:58,200 --> 01:29:00,280 CONSIDER TO BE HARD WIRED 2377 01:29:00,280 --> 01:29:02,240 CIRCUITS TO DRIVE INNATE 2378 01:29:02,240 --> 01:29:03,320 BEHAVIORS. 2379 01:29:03,320 --> 01:29:03,960 MAKING MAPS OF ENVIRONMENTS IS 2380 01:29:03,960 --> 01:29:05,120 JUST NOT ONE OF THOSE THINGS 2381 01:29:05,120 --> 01:29:10,240 BECAUSE ENVIRONMENTS ARE FAR, 2382 01:29:10,240 --> 01:29:12,000 FAR TOO DIVERSE, THERE'S FAR TOO 2383 01:29:12,000 --> 01:29:13,880 MANY DIFFERENT TYPES OF 2384 01:29:13,880 --> 01:29:14,760 ENVIRONMENTS AN ANIMAL CAN 2385 01:29:14,760 --> 01:29:16,080 ENCOUNTER IN ITS LIFETIME AND 2386 01:29:16,080 --> 01:29:16,960 THEY'RE CONSTANTLY CHANGING. 2387 01:29:16,960 --> 01:29:19,400 SO THE HIPPOCAMPUS HAS THE 2388 01:29:19,400 --> 01:29:22,760 FLEXIBILITY TO BUILD THESE MAPS 2389 01:29:22,760 --> 01:29:24,400 OF OUR ENVIRONMENTS AND OUR 2390 01:29:24,400 --> 01:29:25,080 BEHAVIOR WITHIN THOSE 2391 01:29:25,080 --> 01:29:26,360 ENVIRONMENTS ON THE BASIS OF 2392 01:29:26,360 --> 01:29:26,880 EXPERIENCE. 2393 01:29:26,880 --> 01:29:27,920 AND ALL OF THAT, OF COURSE, 2394 01:29:27,920 --> 01:29:32,320 HAPPENS WHEN THE ANIMAL IS AWAKE 2395 01:29:32,320 --> 01:29:33,720 AND WHEN IT'S EXPLORING AND WHEN 2396 01:29:33,720 --> 01:29:34,720 IT GOES TO SLEEP, THERE'S 2397 01:29:34,720 --> 01:29:36,160 SOMETHING CALLED MEMORY 2398 01:29:36,160 --> 01:29:37,240 CONSOLIDATION THAT HAPPENS. 2399 01:29:37,240 --> 01:29:42,840 MEMORY CONSOLIDATION IS BUILT IN 2400 01:29:42,840 --> 01:29:44,480 LARGE MEASURE OR THE 2401 01:29:44,480 --> 01:29:45,360 CONVENTIONAL WISDOM IS IT'S 2402 01:29:45,360 --> 01:29:47,560 BUILT IN LARGE MEASURE ON REPLAY 2403 01:29:47,560 --> 01:29:48,400 OF NEURAL ACTIVITY THAT HAPPENED 2404 01:29:48,400 --> 01:29:49,840 WHILE THE ANIMAL WAS AWAKE WHILE 2405 01:29:49,840 --> 01:29:50,960 THE ANIMAL IS ASLEEP. 2406 01:29:50,960 --> 01:29:56,480 AND THAT REPLAYED ACTIVITY 2407 01:29:56,480 --> 01:29:59,520 ALLOWS FOR ACTIVITY DEPENDENT 2408 01:29:59,520 --> 01:30:01,680 SYNAPTIC PLASTICITY TO CHANGE 2409 01:30:01,680 --> 01:30:03,040 THE WEIGHTS OF THE NETWORKS IN 2410 01:30:03,040 --> 01:30:04,920 THE BRAIN IN A WAY THAT 2411 01:30:04,920 --> 01:30:07,080 REINFORCES OR STORES THOSE 2412 01:30:07,080 --> 01:30:07,920 COGNITIVE MAPS THAT ARE 2413 01:30:07,920 --> 01:30:09,160 BEGINNING TO BE FORMED DURING 2414 01:30:09,160 --> 01:30:15,960 THE ANIMAL'S AWAKE EXPERIENCES. 2415 01:30:15,960 --> 01:30:17,080 THAT'S A HUGE AREA OF INTEREST 2416 01:30:17,080 --> 01:30:18,640 IN THE FIELD, UNDERSTANDING HOW 2417 01:30:18,640 --> 01:30:20,600 REPLAY OF NEURAL ACTIVITY DRIVES 2418 01:30:20,600 --> 01:30:22,120 THE STABILIZATION OF MEMORIES 2419 01:30:22,120 --> 01:30:23,520 THAT IS NECESSARY FOR COGNITIVE 2420 01:30:23,520 --> 01:30:31,640 MAPS TO BE FORMED, IT'S A BIT OF 2421 01:30:31,640 --> 01:30:34,280 A CHALLENGE WITH IMAGING BECAUSE 2422 01:30:34,280 --> 01:30:35,920 THE LIMITATION OF THE TRANSGENIC 2423 01:30:35,920 --> 01:30:38,680 PROBES I DESCRIBED CALLED G CAMP 2424 01:30:38,680 --> 01:30:40,120 IS THEY'RE MEASURING CALCIUM 2425 01:30:40,120 --> 01:30:41,720 INSTEAD OF ELECTRICAL ACTIVITY, 2426 01:30:41,720 --> 01:30:42,720 THEY'RE INHERENTLY SLOWER AND 2427 01:30:42,720 --> 01:30:43,960 SOME OF THE REPLAYED NEURAL 2428 01:30:43,960 --> 01:30:45,360 ACTIVITY IS VERY, VERY FAST, AND 2429 01:30:45,360 --> 01:30:49,160 MUCH MORE DIFFICULT TO IDENTIFY 2430 01:30:49,160 --> 01:30:50,360 SEQUENCES OF SPIKES IN 2431 01:30:50,360 --> 01:30:53,080 POPULATIONS OF NEURONS FROM 2432 01:30:53,080 --> 01:30:56,280 IMAGING THAN FROM ELECTRODES. 2433 01:30:56,280 --> 01:30:57,400 NEVERTHELESS, WE AND OTHERS CAN 2434 01:30:57,400 --> 01:31:00,320 SEE INDICATIONS OF REPLAYED 2435 01:31:00,320 --> 01:31:03,080 ACTIVITY WHILE THE ANIMAL IS 2436 01:31:03,080 --> 01:31:04,240 EITHER RESTING OR SLEEPING, SO 2437 01:31:04,240 --> 01:31:05,160 WE ACTUALLY HAVE NOT DONE IT 2438 01:31:05,160 --> 01:31:08,040 WHETHER THE ANIMAL IS ASLEEP, 2439 01:31:08,040 --> 01:31:09,480 BUT WE CAN SEE IT WHEN THE 2440 01:31:09,480 --> 01:31:10,680 ANIMAL STOPS RUNNING AND IT 2441 01:31:10,680 --> 01:31:11,760 PAUSES AND IT'S IN THE DARK AND 2442 01:31:11,760 --> 01:31:13,280 IT'S RESTING, YOU CAN SEE THIS 2443 01:31:13,280 --> 01:31:17,560 REPLAYED ACTIVITY AS WELLMENT SO 2444 01:31:17,560 --> 01:31:18,800 THE LAST THING I WANT TO HIT ON 2445 01:31:18,800 --> 01:31:21,320 IS THIS WHOLE QUESTION OF 2446 01:31:21,320 --> 01:31:23,200 CONSCIOUSNESS. 2447 01:31:23,200 --> 01:31:24,760 I STUDY MICE SO I DON'T KNOW HOW 2448 01:31:24,760 --> 01:31:25,920 TO MEASURE CONSCIOUSNESS IN 2449 01:31:25,920 --> 01:31:26,400 MICE. 2450 01:31:26,400 --> 01:31:28,640 I CAN'T ASK THEM ABOUT THEIR 2451 01:31:28,640 --> 01:31:31,880 CONSCIOUS EXPERIENCES. 2452 01:31:31,880 --> 01:31:33,840 SO BY AND LARGE, WE ASSUME -- WE 2453 01:31:33,840 --> 01:31:36,800 ASSUME THAT MICE ARE CONSCIOUS, 2454 01:31:36,800 --> 01:31:39,480 BUT -- AND SOME OF THE PROCESSES 2455 01:31:39,480 --> 01:31:41,120 THAT WE'RE MEASURING REFLECT 2456 01:31:41,120 --> 01:31:42,120 CONSCIOUS ACTIVITY IN THE ANIMAL 2457 01:31:42,120 --> 01:31:43,960 BUT WE DON'T KNOW HOW TO DRAW 2458 01:31:43,960 --> 01:31:47,440 THAT LINE FROM NEURAL ACTIVITY 2459 01:31:47,440 --> 01:31:48,320 TO CONSCIOUSNESS BECAUSE IT'S SO 2460 01:31:48,320 --> 01:31:51,000 HARD TO MEASURE THE LATTER. 2461 01:31:51,000 --> 01:31:54,360 >>SO MARCUS, DO YOU SEE SOME 2462 01:31:54,360 --> 01:31:55,600 CONNECTION BETWEEN WHAT NELSON 2463 01:31:55,600 --> 01:32:01,880 HAS BEEN SPEAKING ABOUT AND YOUR 2464 01:32:01,880 --> 01:32:04,360 INTERESTS IN BIG QUESTIONS LIKE 2465 01:32:04,360 --> 01:32:07,400 CONSCIOUSNESS AND MEMORY, BOTH 2466 01:32:07,400 --> 01:32:08,720 IN HEALTH AND IN DISEASE? 2467 01:32:08,720 --> 01:32:09,920 DO YOU WANT TO COMMENT ABOUT 2468 01:32:09,920 --> 01:32:10,280 THAT? 2469 01:32:10,280 --> 01:32:12,720 >>WELL, I WAS ACTUALLY THINKING 2470 01:32:12,720 --> 01:32:15,520 ABOUT A QUESTION I HAVE FOR 2471 01:32:15,520 --> 01:32:16,200 NELSON. 2472 01:32:16,200 --> 01:32:18,480 IT RELATES TO SOMETHING, MAYBE 2473 01:32:18,480 --> 01:32:21,280 I'M DODGING THE ANSWER TO YOUR 2474 01:32:21,280 --> 01:32:24,920 QUESTION, BUT ONE OF THE THINGS 2475 01:32:24,920 --> 01:32:29,040 THAT IS VERY INTERESTING IS THIS 2476 01:32:29,040 --> 01:32:30,240 VARIATION IN BEHAVIOR THAT HAS 2477 01:32:30,240 --> 01:32:32,360 BEEN WELL DOCUMENTED FOR 2478 01:32:32,360 --> 01:32:32,600 DECADES. 2479 01:32:32,600 --> 01:32:34,520 THAT IS IF YOU ASK SOMEBODY TO 2480 01:32:34,520 --> 01:32:37,440 DO A VERY, VERY -- SAY JUST 2481 01:32:37,440 --> 01:32:41,480 PRESS A LITTLE BUTTON AND YOU 2482 01:32:41,480 --> 01:32:44,280 RECORD THE WEIGHT OF YOUR 2483 01:32:44,280 --> 01:32:45,400 PRESSURE, IT VARIES. 2484 01:32:45,400 --> 01:32:47,480 AND THE INTERESTING THING IS, IT 2485 01:32:47,480 --> 01:32:49,360 VARIES ROUGHLY AT THE RATE OF 2486 01:32:49,360 --> 01:32:51,960 INFRA-SLOW ACTIVITY. 2487 01:32:51,960 --> 01:32:55,160 NOW, THE QUESTION IS, WHAT'S THE 2488 01:32:55,160 --> 01:32:55,600 ADVANTAGE? 2489 01:32:55,600 --> 01:32:58,560 WHY ARE WE -- WHY ARE WE NOT 2490 01:32:58,560 --> 01:33:00,560 JUST CONSISTENT ALL THE TIME? 2491 01:33:00,560 --> 01:33:02,320 AND AS NELSON WAS JUST TALKING 2492 01:33:02,320 --> 01:33:03,760 ABOUT, THERE ARE THESE TWO 2493 01:33:03,760 --> 01:33:06,000 STATES OF THE HIPPOCAMPUS, THE 2494 01:33:06,000 --> 01:33:11,080 THI TA THETASTATE AND SHARP WAVE 2495 01:33:11,080 --> 01:33:12,120 STATE. 2496 01:33:12,120 --> 01:33:13,640 OFTEN ONE THINKS ABOUT THIS IN 2497 01:33:13,640 --> 01:33:14,960 THE CONTEXT OF SLOW WAVE SLEEP 2498 01:33:14,960 --> 01:33:16,920 AND IN PARTICULAR, WHERE YOU 2499 01:33:16,920 --> 01:33:19,280 REVERSE THESE STATES, PRESUMABLY 2500 01:33:19,280 --> 01:33:21,240 AS YOU ELOQUENTLY DESCRIBED A 2501 01:33:21,240 --> 01:33:21,520 MOMENT AGO. 2502 01:33:21,520 --> 01:33:23,440 BUT WE HAVE THIS VARIABILITY 2503 01:33:23,440 --> 01:33:26,920 GOING ON ALMOST AS IF YOU'RE 2504 01:33:26,920 --> 01:33:30,680 VARYING N IN AROUSAL STATE WHILE 2505 01:33:30,680 --> 01:33:31,240 YOU'RE AWAKE. 2506 01:33:31,240 --> 01:33:32,440 THE QUESTION THAT'S OCCURRED TO 2507 01:33:32,440 --> 01:33:36,600 ME IS, ARE WE GOING THROUGH THAT 2508 01:33:36,600 --> 01:33:38,800 SHARP WAVE RIPPLE STATE VERSUS 2509 01:33:38,800 --> 01:33:40,120 THETA STATE ALL THE TIME WHEN 2510 01:33:40,120 --> 01:33:41,400 WE'RE AWAKE? 2511 01:33:41,400 --> 01:33:42,760 AND THIS KIND OF COMES OUT OF 2512 01:33:42,760 --> 01:33:45,520 THAT SLIDE I SHOWED OF DAVID 2513 01:33:45,520 --> 01:33:46,280 MCCORMICK'S WORK WHERE IT WAS 2514 01:33:46,280 --> 01:33:48,040 TUCKED IN A CORNER, BUT IT'S 2515 01:33:48,040 --> 01:33:50,520 ALWAYS STRUCK ME THAT IF I'M 2516 01:33:50,520 --> 01:33:53,280 GOING TO REMEMBER SOMETHING, I 2517 01:33:53,280 --> 01:33:55,720 WANT TO RECORD IT FAIRLY 2518 01:33:55,720 --> 01:33:56,120 IMMEDIATELY. 2519 01:33:56,120 --> 01:33:57,920 I DON'T WANT TO HAVE TO GO TO 2520 01:33:57,920 --> 01:34:01,080 BED TONIGHT TO HOPE THAT I CAN 2521 01:34:01,080 --> 01:34:02,600 REMEMBER A DAY'S WORTH, HOW 2522 01:34:02,600 --> 01:34:04,280 ABOUT DOING IT SEVERAL TIMES A 2523 01:34:04,280 --> 01:34:07,880 MINUTE? 2524 01:34:07,880 --> 01:34:09,240 WE DON'T HAVE DIRECT DATA THAT 2525 01:34:09,240 --> 01:34:10,200 WOULD SPEAK TO THAT AT THE 2526 01:34:10,200 --> 01:34:13,080 MOMENT, BUT I WOULD THINK MAYBE, 2527 01:34:13,080 --> 01:34:13,960 NELSON, YOU'VE EITHER THOUGHT 2528 01:34:13,960 --> 01:34:14,920 ABOUT THIS OR NOT. 2529 01:34:14,920 --> 01:34:17,240 I'M JUST ASKING FOR MY OWN 2530 01:34:17,240 --> 01:34:19,240 EDIFICATION HERE, IS THAT THE 2531 01:34:19,240 --> 01:34:20,520 VARIABILITY IN HUMAN BEHAVIOR, 2532 01:34:20,520 --> 01:34:22,840 WHICH HAS BEEN DOCUMENTED FOR 2533 01:34:22,840 --> 01:34:26,480 DECADES, SUBTLE AS IT MAY BE, 2534 01:34:26,480 --> 01:34:29,440 IT'S THE PRICE WE PAY FOR 2535 01:34:29,440 --> 01:34:30,640 ENHANCING THE MEMORY OF THE 2536 01:34:30,640 --> 01:34:31,640 MOMENT. 2537 01:34:31,640 --> 01:34:36,120 IF YOU WILL. 2538 01:34:36,120 --> 01:34:38,400 >>YEAH, I MEAN IT'S DEFINITELY 2539 01:34:38,400 --> 01:34:39,320 TRUE THAT SHARP WAVE EVENTS, 2540 01:34:39,320 --> 01:34:40,520 WHICH ARE THE EVENTS THAT HAPPEN 2541 01:34:40,520 --> 01:34:43,480 WHEN THE ANIMAL IS SLEEPING ALSO 2542 01:34:43,480 --> 01:34:47,880 HAPPEN WHEN THE ANIMAL IS AWAKE 2543 01:34:47,880 --> 01:34:49,760 BUT IN A LESS AROUSED STATE. 2544 01:34:49,760 --> 01:34:52,920 SO TYPICALLY MICE, WHEN THEY'RE 2545 01:34:52,920 --> 01:34:53,640 RUNNING, FOR EXAMPLE, AND 2546 01:34:53,640 --> 01:34:55,680 THEY'RE MOVING AROUND AND 2547 01:34:55,680 --> 01:34:56,480 EXPLORING THEIR ENVIRONMENT, 2548 01:34:56,480 --> 01:34:59,080 THEY DO NOT EXHIBIT SHARP WAVE 2549 01:34:59,080 --> 01:35:03,480 RIPPLES, BUT WHEN THEY STOP AND 2550 01:35:03,480 --> 01:35:06,640 PAUSE, THERE ARE SOMETHING 2551 01:35:06,640 --> 01:35:08,040 CALLED AWAKE SHARP WAVE RIPPLES. 2552 01:35:08,040 --> 01:35:10,360 SO IT DOES HAPPEN DURING THE 2553 01:35:10,360 --> 01:35:12,680 ANIMAL'S AWAKE STATE WHILE IT'S 2554 01:35:12,680 --> 01:35:15,840 EXPLORING, USUALLY IN A SLIGHTLY 2555 01:35:15,840 --> 01:35:17,400 LESS AROUSED STATE THAN WHEN 2556 01:35:17,400 --> 01:35:18,520 THEY'RE ACTUALLY RUNNING AND 2557 01:35:18,520 --> 01:35:20,680 EXPLORING. 2558 01:35:20,680 --> 01:35:23,440 AND IT HAS BEEN SHOWN BY LAUREN 2559 01:35:23,440 --> 01:35:25,760 FRANK'S LAB AT UCSF THAT IF YOU 2560 01:35:25,760 --> 01:35:27,840 INTERFERE WITH THOSE SHARP WAVE 2561 01:35:27,840 --> 01:35:29,360 RIPPLES IN THE AWAKE STATE, THAT 2562 01:35:29,360 --> 01:35:31,480 IT INTERFERES WITH THE ANIMAL'S 2563 01:35:31,480 --> 01:35:33,200 ABILITY TO FORM MEMORIES. 2564 01:35:33,200 --> 01:35:34,880 SO THERE'S DEFINITELY AN 2565 01:35:34,880 --> 01:35:35,320 INTERPLAY. 2566 01:35:35,320 --> 01:35:36,640 IT'S ALSO BEEN SHOWN THAT 2567 01:35:36,640 --> 01:35:37,960 INTERFERING WITH SHARP WAVE 2568 01:35:37,960 --> 01:35:39,080 RIPPLES DURING SLEEP INTERFERES 2569 01:35:39,080 --> 01:35:41,040 WITH MEMORY, SO THERE'S AN 2570 01:35:41,040 --> 01:35:43,240 INTERPLAY BETWEEN THOSE TWO 2571 01:35:43,240 --> 01:35:44,720 THINGS. 2572 01:35:44,720 --> 01:35:47,840 IT SEEMS LIKE A GOOD HYPOTHESIS 2573 01:35:47,840 --> 01:35:50,000 IS THAT SHARP WAVE RIPPLES SORT 2574 01:35:50,000 --> 01:35:52,040 OF LABEL POPULATIONS OF NEURONS 2575 01:35:52,040 --> 01:35:56,520 AND SYNAPSES FOR SYNAPTIC 2576 01:35:56,520 --> 01:35:57,720 PLASTICITY, THE PROCESS GETS 2577 01:35:57,720 --> 01:35:59,200 STARTED AND THEN IT GETS 2578 01:35:59,200 --> 01:36:00,040 REINFORCED AT NIGHT IN THOSE 2579 01:36:00,040 --> 01:36:03,120 SAME POPULATIONS OF CELLS. 2580 01:36:03,120 --> 01:36:05,800 OR DURING SLEEP. 2581 01:36:05,800 --> 01:36:08,400 >>THAT'S VERY INTERESTING. 2582 01:36:08,400 --> 01:36:11,160 YOU KNOW, ONE OF THE SURPRISING 2583 01:36:11,160 --> 01:36:12,240 FINDINGS THAT WE HAD EARLY ON IN 2584 01:36:12,240 --> 01:36:15,520 ALL THIS IMAGING WORK WERE THESE 2585 01:36:15,520 --> 01:36:16,400 ANTICORRELATIONS, AND THERE WAS 2586 01:36:16,400 --> 01:36:18,160 A BIG FUSS ABOUT WHETHER THEY 2587 01:36:18,160 --> 01:36:20,160 WERE ARTIFACT OR THEY WEREN'T, 2588 01:36:20,160 --> 01:36:23,360 BUT THEY INVOLVE NOT THE PRIMARY 2589 01:36:23,360 --> 01:36:24,920 SENSORY MOTOR CORTICES, BUT THEY 2590 01:36:24,920 --> 01:36:25,840 INVOLVE THINGS LIKE THE 2591 01:36:25,840 --> 01:36:28,400 ANTERIOR -- OR THE ATTENTION 2592 01:36:28,400 --> 01:36:30,840 NETWORKS, THERE'S TWO OF THEM, 2593 01:36:30,840 --> 01:36:33,880 AND THIS HI HIPPOCAMPAL CORTICAL 2594 01:36:33,880 --> 01:36:36,240 MEMORY SYSTEM AND THEY'RE 2595 01:36:36,240 --> 01:36:38,320 ALTERNATING ALL THE TIME. 2596 01:36:38,320 --> 01:36:42,360 AND THE QUESTION IS, AGAIN, WHY 2597 01:36:42,360 --> 01:36:44,720 IS THIS AN EFFICIENT WAY OF, IF 2598 01:36:44,720 --> 01:36:46,560 YOU WILL, KEEPING TRACK OF 2599 01:36:46,560 --> 01:36:50,960 WHAT'S GOING ON AS YOU NAVIGATE 2600 01:36:50,960 --> 01:36:52,880 THE DAY YOU'RE UNDERTAKING. 2601 01:36:52,880 --> 01:36:54,960 BECAUSE WE'RE PAYING A PRICE FOR 2602 01:36:54,960 --> 01:36:55,800 IT, OBVIOUSLY. 2603 01:36:55,800 --> 01:37:02,120 WE'RE NOT TOTALLY CONSISTENT IN, 2604 01:37:02,120 --> 01:37:03,440 AND THERE HAS TO BE SOME SORT OF 2605 01:37:03,440 --> 01:37:04,720 A REASONING FOR THAT BEING BUILT 2606 01:37:04,720 --> 01:37:09,480 INTO THE SYSTEM. 2607 01:37:09,480 --> 01:37:11,080 IN ALZHEIMER'S DISEASE, THIS 2608 01:37:11,080 --> 01:37:12,640 WHOLE PROCESS HAS RADICALLY 2609 01:37:12,640 --> 01:37:13,720 CHANGED. 2610 01:37:13,720 --> 01:37:16,480 SO THAT YOU HAVE THESE ONSET AND 2611 01:37:16,480 --> 01:37:17,480 OFFSET CON ASSISTANTS HAVING TO 2612 01:37:17,480 --> 01:37:19,680 DO WITH DEPRESSION OF THE 2613 01:37:19,680 --> 01:37:22,840 DEFAULT MODE NETWORK, AND YOU 2614 01:37:22,840 --> 01:37:24,160 HAVE -- IN ALZHEIMER'S, YOU HAVE 2615 01:37:24,160 --> 01:37:26,920 AN ONSET AND IT NEVER GOES DOWN. 2616 01:37:26,920 --> 01:37:29,680 YOU NEVER TRANSITION FROM THESE 2617 01:37:29,680 --> 01:37:32,320 ONE STATE TO THE OTHER. 2618 01:37:32,320 --> 01:37:35,840 IT'S COMPLETELY BOLIXED UP. 2619 01:37:35,840 --> 01:37:36,960 WHICH MIGHT BE PART OF THE 2620 01:37:36,960 --> 01:37:37,320 MEMORY PROCESS. 2621 01:37:37,320 --> 01:37:39,040 >>I THINK BEHAVIORAL 2622 01:37:39,040 --> 01:37:42,200 CONSISTENCY IS NOT NECESSARILY 2623 01:37:42,200 --> 01:37:43,240 THE GOAL EITHER, BECAUSE IF 2624 01:37:43,240 --> 01:37:44,400 YOU'RE TRYING TO LEARN FROM YOUR 2625 01:37:44,400 --> 01:37:45,480 EXPERIENCES, YOU WANT TO TRY 2626 01:37:45,480 --> 01:37:47,360 SOME THINGS OUT. 2627 01:37:47,360 --> 01:37:50,480 AND SO WE'VE SEEN INDICATIONS OF 2628 01:37:50,480 --> 01:37:53,440 THAT IN MOUSE BEHAVIOR ALSO, 2629 01:37:53,440 --> 01:37:54,760 THAT THEY'LL SETTLE INTO A 2630 01:37:54,760 --> 01:37:56,760 PATTERN OF DOING THE SAME THING 2631 01:37:56,760 --> 01:37:59,800 OVER AND OVER AGAIN, WHEN THAT 2632 01:37:59,800 --> 01:38:00,800 THING THAT THEY'RE DOING IS 2633 01:38:00,800 --> 01:38:02,160 ACTUALLY NOT THE MOST EFFICIENT 2634 01:38:02,160 --> 01:38:03,800 THING THEY COULD BE DOING, AND 2635 01:38:03,800 --> 01:38:05,440 THEN THEY SOMEHOW MANAGE TO 2636 01:38:05,440 --> 01:38:08,200 BREAK OUT OF THAT. 2637 01:38:08,200 --> 01:38:10,600 AND THEY'RE ONLY ABLE TO BREAK 2638 01:38:10,600 --> 01:38:12,840 OUT OF THAT BECAUSE THEY VARY 2639 01:38:12,840 --> 01:38:13,800 THEIR OWN BEHAVIOR AND THEY 2640 01:38:13,800 --> 01:38:15,640 EXPLORE A LITTLE BIT AND THEN 2641 01:38:15,640 --> 01:38:16,880 THEY REALIZE, THROUGH 2642 01:38:16,880 --> 01:38:18,440 EXPLORATION, THAT, OH, THERE'S 2643 01:38:18,440 --> 01:38:20,560 MAYBE A MORE EFFICIENT APPROACH 2644 01:38:20,560 --> 01:38:23,120 TO DOING THIS BEHAVIOR. 2645 01:38:23,120 --> 01:38:24,600 AND THAT'S ONE OF THE REALLY 2646 01:38:24,600 --> 01:38:26,360 REMARKABLE THINGS TO ME, THIS 2647 01:38:26,360 --> 01:38:29,200 DATES ALL THE WAY BACK TO PEOPLE 2648 01:38:29,200 --> 01:38:30,360 STUDYING RODENTS, YOU KNOW, BACK 2649 01:38:30,360 --> 01:38:33,320 IN THE 20s AND 30s AND 2650 01:38:33,320 --> 01:38:36,800 TOLLMAN IN THE 40s, THAT THEY 2651 01:38:36,800 --> 01:38:39,040 OBSERVE PERSEVERATION OF ANIMALS 2652 01:38:39,040 --> 01:38:42,120 IN A RELATIVELY INEFFICIENT 2653 01:38:42,120 --> 01:38:44,240 BEHAVIORAL MODE, AND THEN AFTER 2654 01:38:44,240 --> 01:38:46,000 TIME, THEY'LL BREAK OUT OF THAT. 2655 01:38:46,000 --> 01:38:47,760 AND THEY'LL START PERFORMING 2656 01:38:47,760 --> 01:38:48,640 MORE EFFICIENTLY. 2657 01:38:48,640 --> 01:38:49,840 AGAIN, THEY WOULDN'T BE ABLE TO 2658 01:38:49,840 --> 01:38:52,480 DO THAT IF THEY DIDN'T VARY 2659 01:38:52,480 --> 01:38:54,360 THEIR BEHAVIOR. 2660 01:38:54,360 --> 01:38:59,160 >>I THINK, YEAH, THESE 2661 01:38:59,160 --> 01:39:00,040 VARIABILITIES ARE TREATED AS 2662 01:39:00,040 --> 01:39:01,920 KIND OF A NUISANCE, AND YOU 2663 01:39:01,920 --> 01:39:05,240 KNOW, WHY WOULD YOU DESIGN 2664 01:39:05,240 --> 01:39:06,880 SOMETHING, LEAVES ME WITH THE 2665 01:39:06,880 --> 01:39:08,280 FEELING THAT THEY'RE VERY 2666 01:39:08,280 --> 01:39:08,760 PURPOSEFUL. 2667 01:39:08,760 --> 01:39:11,200 THERE IS SOMETHING THAT IS 2668 01:39:11,200 --> 01:39:13,040 FUNDAMENTALLY A PROPERTY OF THIS 2669 01:39:13,040 --> 01:39:15,120 SYSTEM THAT HAS TO CALL TIME OUT 2670 01:39:15,120 --> 01:39:16,440 PERIODICALLY TO GET SOMETHING 2671 01:39:16,440 --> 01:39:18,360 RIGHT. 2672 01:39:18,360 --> 01:39:22,520 AND SO THIS IS WHERE YOUR LEVEL 2673 01:39:22,520 --> 01:39:24,280 OF INVESTIGATION COULD FILL IN A 2674 01:39:24,280 --> 01:39:27,280 BIG GAP BETWEEN WHAT WE LOOK AT 2675 01:39:27,280 --> 01:39:30,440 IN A VERY LARGE GROSS LEVEL, 2676 01:39:30,440 --> 01:39:33,520 PROBABLY HAS SOME VERY DETAILED 2677 01:39:33,520 --> 01:39:35,760 SPECIFIC ISSUES THAT FIT RIGHT 2678 01:39:35,760 --> 01:39:41,680 INTO YOUR GLOVE BOX. 2679 01:39:41,680 --> 01:39:44,600 >>TRADITIONALLY IN BEHAVIORAL 2680 01:39:44,600 --> 01:39:45,920 NEUROSCIENCE, PEOPLE WILL HAVE 2681 01:39:45,920 --> 01:39:47,280 ANIMALS PERFORM TASKS AND 2682 01:39:47,280 --> 01:39:49,360 THEY'LL CLASSIFY BEHAVIOR AS 2683 01:39:49,360 --> 01:39:51,960 CORRECT OR INCORRECT, AND YOU 2684 01:39:51,960 --> 01:39:53,280 HAVE TO SOMETIMES QUESTION 2685 01:39:53,280 --> 01:39:54,440 WHETHER INCORRECT IS THE RIGHT 2686 01:39:54,440 --> 01:39:56,120 WORD TO DESCRIBE THEIR BEHAVIOR, 2687 01:39:56,120 --> 01:39:57,800 IF THEY'RE, IN FACT, EXPLORING. 2688 01:39:57,800 --> 01:40:02,000 SO I REMEMBER THE COLLEAGUE 2689 01:40:02,000 --> 01:40:04,440 ANDRE FENTON AT NYU DESCRIBING 2690 01:40:04,440 --> 01:40:05,520 AN EXPERIMENT WHERE THE RATS HAD 2691 01:40:05,520 --> 01:40:06,960 TO MOVE AROUND IN A CERTAIN WAY 2692 01:40:06,960 --> 01:40:09,320 TO AVOID GETTING SHOCKED, AND 2693 01:40:09,320 --> 01:40:11,040 THEN EVERY NOW AND THEN, THEY 2694 01:40:11,040 --> 01:40:13,440 WOULD APPROACH THE SHOCK ZONE 2695 01:40:13,440 --> 01:40:14,680 AND TEST IT AND SEE IF THEY 2696 01:40:14,680 --> 01:40:16,000 WOULD STILL GET SHOCKED BECAUSE 2697 01:40:16,000 --> 01:40:17,640 THEY HAD TO DO SO MUCH WORK TO 2698 01:40:17,640 --> 01:40:18,760 AVOID THE SHOCK ZONE THAT THEY 2699 01:40:18,760 --> 01:40:20,880 THOUGHT IT SEEMED -- MAYBE 2700 01:40:20,880 --> 01:40:22,640 SEEMED WORTH TO CHECK ONCE AND A 2701 01:40:22,640 --> 01:40:24,040 WHILE IF THEY STILL REALLY 2702 01:40:24,040 --> 01:40:25,040 NEEDED TO DO ALL THAT WORK. 2703 01:40:25,040 --> 01:40:27,040 SO YOU KNOW, THAT'S NOT 2704 01:40:27,040 --> 01:40:28,120 NECESSARILY A MISTAKE ON THE 2705 01:40:28,120 --> 01:40:29,840 PART OF THE ANIMAL, IT'S JUST 2706 01:40:29,840 --> 01:40:30,120 EXPLORATION. 2707 01:40:30,120 --> 01:40:32,800 >>YES. 2708 01:40:32,800 --> 01:40:34,320 THIS IS VERY, VERY INTERESTING. 2709 01:40:34,320 --> 01:40:40,120 I MUST SAY, THIS IS WHERE GOING 2710 01:40:40,120 --> 01:40:42,120 BACK AND LOOK AT SOME OF THIS 2711 01:40:42,120 --> 01:40:45,120 EARLY WORK, GOING BACK AND 2712 01:40:45,120 --> 01:40:48,560 READING ON INFRASLOW 2713 01:40:48,560 --> 01:40:49,160 FLUCTUATIONS. 2714 01:40:49,160 --> 01:40:50,160 THE INSIGHT IN SOME OF THIS WORK 2715 01:40:50,160 --> 01:40:52,360 IS REALLY REMARKABLE, AND YET IT 2716 01:40:52,360 --> 01:40:54,440 JUST KIND OF GOT LOST IN THE 2717 01:40:54,440 --> 01:40:56,240 DUST BIN OF HISTORY. 2718 01:40:56,240 --> 01:40:58,960 >>IT REALLY IS, IT'S 2719 01:40:58,960 --> 01:40:59,840 INCREDIBLE, WHAT PEOPLE HAVE 2720 01:40:59,840 --> 01:41:02,120 BEEN ABLE TO -- WERE ABLE TO DO 2721 01:41:02,120 --> 01:41:04,480 MANY DECADES AGO WITH, YOU KNOW, 2722 01:41:04,480 --> 01:41:05,800 VERY RUDIMENTARY TOOLS. 2723 01:41:05,800 --> 01:41:06,240 >>YES. 2724 01:41:06,240 --> 01:41:08,000 >>AND NOW, YOU KNOW, HERE WE 2725 01:41:08,000 --> 01:41:10,320 ARE AT THIS POINT IN TIME IN 2726 01:41:10,320 --> 01:41:11,520 NEUROSCIENCE WHERE THE TOOLS ARE 2727 01:41:11,520 --> 01:41:12,280 INCREDIBLE. 2728 01:41:12,280 --> 01:41:14,520 THE TOOLS THAT YOU TALKED ABOUT, 2729 01:41:14,520 --> 01:41:17,680 THAT ALLOW US TO, YOU KNOW, 2730 01:41:17,680 --> 01:41:20,240 INTERROGATE HUMANS WITHOUT DOING 2731 01:41:20,240 --> 01:41:23,080 ANYTHING DISRUPTIVE AT ALL TO 2732 01:41:23,080 --> 01:41:27,440 THE BRAIN, TO DETAILED 2733 01:41:27,440 --> 01:41:30,080 ANATOMICAL PHYSIOLOGICAL AND 2734 01:41:30,080 --> 01:41:31,800 PERTURBATIONS THAT WE CAN MAKE 2735 01:41:31,800 --> 01:41:34,400 IN ANIMALS LIKE MICE AND FLIES 2736 01:41:34,400 --> 01:41:35,040 AND FISH. 2737 01:41:35,040 --> 01:41:36,360 IT'S EXTRAORDINARY, WHAT WE CAN 2738 01:41:36,360 --> 01:41:37,480 DO NOW. 2739 01:41:37,480 --> 01:41:40,040 AND I WANT TO EMPHASIZE ONE 2740 01:41:40,040 --> 01:41:43,520 OTHER THING WHICH SORT OF 2741 01:41:43,520 --> 01:41:46,840 APPROACHES -- IS COMPUTATION AND 2742 01:41:46,840 --> 01:41:47,960 THEORY. 2743 01:41:47,960 --> 01:41:49,080 ANSWERING THIS QUESTION, AGAIN, 2744 01:41:49,080 --> 01:41:50,560 HOW DOES THE BRAIN WORK MEANS WE 2745 01:41:50,560 --> 01:41:51,480 HAVE TO COLLECT INFORMATION FROM 2746 01:41:51,480 --> 01:41:53,000 A VAST NUMBER OF STUDIES AND 2747 01:41:53,000 --> 01:41:55,120 BRING IT TOGETHER SOMEHOW IN A 2748 01:41:55,120 --> 01:41:57,520 MEANINGFUL WAY, AND I THINK THAT 2749 01:41:57,520 --> 01:42:00,640 HAVING COMPUTATIONAL MODELS OF 2750 01:42:00,640 --> 01:42:01,720 SYSTEMS AND USING THOSE MODELS 2751 01:42:01,720 --> 01:42:03,680 TO MAKE EXPERIMENTALLY TESTABLE 2752 01:42:03,680 --> 01:42:05,040 PREDICTIONS AND USING THE MODELS 2753 01:42:05,040 --> 01:42:06,360 ESSENTIALLY TO ASK OURSELVES, 2754 01:42:06,360 --> 01:42:08,000 WELL, DO WE REALLY UNDERSTAND 2755 01:42:08,000 --> 01:42:09,840 THIS SYSTEM AS WELL AS WE THINK 2756 01:42:09,840 --> 01:42:13,640 WE DO, IS A SUPER IMPORTANT 2757 01:42:13,640 --> 01:42:16,360 APPROACH, AND THEN THEORY, YOU 2758 01:42:16,360 --> 01:42:18,280 KNOW, I NOTICED IN THE CHAT, 2759 01:42:18,280 --> 01:42:19,440 THERE WAS SOME COMMENTS ABOUT 2760 01:42:19,440 --> 01:42:21,120 THE THEORY OF RELATIVITY AND I 2761 01:42:21,120 --> 01:42:22,840 DON'T KNOW EXACTLY HOW THAT 2762 01:42:22,840 --> 01:42:25,480 RELATES TO NEUROSCIENCE, BUT YOU 2763 01:42:25,480 --> 01:42:28,320 KNOW, THE IDEA IN PHYSICS IS 2764 01:42:28,320 --> 01:42:31,200 THAT IF THEORY REPRESENTS OUR 2765 01:42:31,200 --> 01:42:32,000 UNDERSTANDING OF THE WORLD, IF 2766 01:42:32,000 --> 01:42:33,840 WE HAVE A THEORY, THEN THAT'S 2767 01:42:33,840 --> 01:42:36,880 SORT OF OUR BEST CASE 2768 01:42:36,880 --> 01:42:39,040 UNDERSTANDING OR CURRENT 2769 01:42:39,040 --> 01:42:40,680 UNDERSTANDING OF THE WORLD WE 2770 01:42:40,680 --> 01:42:41,880 WANT TO UNDERSTAND OR THE SYSTEM 2771 01:42:41,880 --> 01:42:43,560 WE WANT TO UNDERSTAND. 2772 01:42:43,560 --> 01:42:44,560 AND NEUROSCIENCE, I THINK, NEEDS 2773 01:42:44,560 --> 01:42:45,240 MORE OF THAT. 2774 01:42:45,240 --> 01:42:46,880 THERE'S A LOT OF -- 2775 01:42:46,880 --> 01:42:49,080 >>I'M GETTING AN EDUCATION 2776 01:42:49,080 --> 01:42:53,920 ALONG THIS LINE IN THAT MY LAST 2777 01:42:53,920 --> 01:42:56,440 GRADUATE STUDENT RYAN RAUT IS AT 2778 01:42:56,440 --> 01:42:57,120 THE ALLEN INSTITUTE IT THE 2779 01:42:57,120 --> 01:42:58,160 UNIVERSITY OF WASHINGTON IN A 2780 01:42:58,160 --> 01:42:59,920 COMBINED PROGRAM ON THEORETICAL 2781 01:42:59,920 --> 01:43:02,320 NEUROBIOLOGY. 2782 01:43:02,320 --> 01:43:03,040 LARGE SYSTEM COMPLEXITY. 2783 01:43:03,040 --> 01:43:06,120 AND WE HAVE LUNCH, NOW I'M THE 2784 01:43:06,120 --> 01:43:09,160 STUDENT AND HE IS THE TEACHER. 2785 01:43:09,160 --> 01:43:10,680 BUT I THINK IT'S DEEPLY 2786 01:43:10,680 --> 01:43:12,840 PROMISING, WHEN YOU THINK OF 2787 01:43:12,840 --> 01:43:14,560 THESE VERY LARGE COMPLEX 2788 01:43:14,560 --> 01:43:17,080 SYSTEMS, HOW YOU BEGIN TO THINK 2789 01:43:17,080 --> 01:43:19,080 ABOUT THEM, AND PEOPLE HAVE BEEN 2790 01:43:19,080 --> 01:43:20,960 THINKING ABOUT THIS KIND OF 2791 01:43:20,960 --> 01:43:22,320 THING AND GETTING IT FOCUSED ON 2792 01:43:22,320 --> 01:43:24,920 THE BRAIN, I THINK, IS A VERY 2793 01:43:24,920 --> 01:43:25,840 IMPORTANT AVENUE GOING FORWARD 2794 01:43:25,840 --> 01:43:29,560 HERE. 2795 01:43:29,560 --> 01:43:31,160 >>LET ME INTERJECT FOR A MINUTE 2796 01:43:31,160 --> 01:43:31,400 HERE. 2797 01:43:31,400 --> 01:43:34,800 WE HAVE A COUPLE OF QUESTIONS 2798 01:43:34,800 --> 01:43:38,440 THAT ARE MORE -- THAT HAVE BEEN 2799 01:43:38,440 --> 01:43:38,880 SUBMITTED. 2800 01:43:38,880 --> 01:43:47,200 FOR EXAMPLE, NELSON, BOB ASKS, 2801 01:43:47,200 --> 01:43:52,920 YOU SHOWED AN ARTIFICIAL NEURAL 2802 01:43:52,920 --> 01:43:56,080 NETWORK WITH A SIMPLE LINEAR 2803 01:43:56,080 --> 01:43:57,120 NODAL FUNCTION. 2804 01:43:57,120 --> 01:43:58,320 HAVE ARTIFICIAL NEURAL NETWORKS 2805 01:43:58,320 --> 01:44:01,920 WITH NON-LINEAR NODAL FUNCTIONS 2806 01:44:01,920 --> 01:44:03,800 BEEN SHOWN TO PRODUCE MORE 2807 01:44:03,800 --> 01:44:06,240 REALISTIC RESPONSES? 2808 01:44:06,240 --> 01:44:08,200 >>YEAH, I SAW THAT QUESTION. 2809 01:44:08,200 --> 01:44:09,880 SO ACTUALLY, MOST NEURAL 2810 01:44:09,880 --> 01:44:12,160 NETWORKS DO CONTAIN 2811 01:44:12,160 --> 01:44:12,520 NON-LINEARITIES. 2812 01:44:12,520 --> 01:44:16,240 THERE WAS THIS CONCEPT I SHOWED 2813 01:44:16,240 --> 01:44:19,320 CALLED THE RECTIFYING LINEAR 2814 01:44:19,320 --> 01:44:21,760 UNIT, AND THAT IS FUNDAMENTALLY 2815 01:44:21,760 --> 01:44:23,080 A NON-LINEARITY BECAUSE THERE'S 2816 01:44:23,080 --> 01:44:26,280 A THRESHOLD, BUT IT IS LINEAR 2817 01:44:26,280 --> 01:44:29,000 ABOVE THRESHOLD. 2818 01:44:29,000 --> 01:44:31,640 SO THERE ARE LOTS OF DIFFERENT 2819 01:44:31,640 --> 01:44:33,680 VARIATIONS ON THE RECTIFYING 2820 01:44:33,680 --> 01:44:35,080 LINEAR UNIT THAT HAVE BEEN 2821 01:44:35,080 --> 01:44:36,160 INCORPORATED INTO ARTIFICIAL 2822 01:44:36,160 --> 01:44:37,520 NEURAL NETWORKS. 2823 01:44:37,520 --> 01:44:41,360 IT DOES AFFECT THE WAY A.I. 2824 01:44:41,360 --> 01:44:42,000 SYSTEMS PERFORM. 2825 01:44:42,000 --> 01:44:44,200 I WOULD HESITATE TO SAY WHETHER 2826 01:44:44,200 --> 01:44:46,200 THAT MEANS THEY PRODUCE MORE 2827 01:44:46,200 --> 01:44:48,800 REALISTIC RESPONSES. 2828 01:44:48,800 --> 01:44:52,600 IT JUST MEANS THAT THERE ARE 2829 01:44:52,600 --> 01:44:54,880 COMPUTATIONAL TRICKS THAT CAN BE 2830 01:44:54,880 --> 01:44:57,480 USED IN A.I. SYSTEMS TO IMPROVE 2831 01:44:57,480 --> 01:44:58,800 THEIR PERFORMANCE. 2832 01:44:58,800 --> 01:45:01,920 NOW, YOU KNOW, AN EXAMPLE OF 2833 01:45:01,920 --> 01:45:04,360 THAT, IS THERE SOMETHING -- A 2834 01:45:04,360 --> 01:45:06,360 CONCEPT CALLED A REGULARIZATION. 2835 01:45:06,360 --> 01:45:09,440 AND REGULARIZATIONS ARE 2836 01:45:09,440 --> 01:45:11,000 ESSENTIALLY NOISE THAT 2837 01:45:11,000 --> 01:45:12,840 INTRODUCED PERIODICALLY INTO THE 2838 01:45:12,840 --> 01:45:13,160 SYSTEM. 2839 01:45:13,160 --> 01:45:16,640 AND THE REASON FOR THAT IS, 2840 01:45:16,640 --> 01:45:18,040 ESSENTIALLY ARTIFICIAL NEURAL 2841 01:45:18,040 --> 01:45:21,640 NETWORKS ARE GIGANTIC FITTING 2842 01:45:21,640 --> 01:45:22,800 FUNCTIONS, AND THOSE FITTING 2843 01:45:22,800 --> 01:45:27,600 FUNCTIONS WILL FIND LOCAL MINIMA 2844 01:45:27,600 --> 01:45:28,840 AND GET STUCK IN THEM, SO ONE 2845 01:45:28,840 --> 01:45:30,200 WAY OF IMPROVING THE FUNCTION OF 2846 01:45:30,200 --> 01:45:31,680 A NEURAL NETWORK IS TO PUSH IT 2847 01:45:31,680 --> 01:45:34,120 OUT OF LOCAL MINIMA BY 2848 01:45:34,120 --> 01:45:34,680 INTRODUCING NOISE ONCE IN A 2849 01:45:34,680 --> 01:45:36,720 WHILE. 2850 01:45:36,720 --> 01:45:40,320 SO THESE ARE -- THESE KINDS OF 2851 01:45:40,320 --> 01:45:41,720 VARIATIONS ON ARTIFICIAL NEURAL 2852 01:45:41,720 --> 01:45:44,280 NETWORKS HAVE BEEN EXPLORED 2853 01:45:44,280 --> 01:45:46,920 EXTENSIVELY BY THE FIELD, AND IN 2854 01:45:46,920 --> 01:45:49,200 FACT, ARE IN LARGE MEASURE 2855 01:45:49,200 --> 01:45:50,680 RESPONSIBLE FOR SOME OF THE 2856 01:45:50,680 --> 01:45:52,680 IMPROVEMENTS THAT WE SEE 2857 01:45:52,680 --> 01:45:54,640 HAPPENING VERY RAPIDLY IN THE 2858 01:45:54,640 --> 01:45:57,480 LAST FEW YEARS. 2859 01:45:57,480 --> 01:45:59,400 THE OTHER THING THAT HAS LED TO 2860 01:45:59,400 --> 01:46:01,040 THE RAPID IMPROVEMENT, IT'S JUST 2861 01:46:01,040 --> 01:46:02,360 MASSIVE SCALING UP OF THESE 2862 01:46:02,360 --> 01:46:03,640 SYSTEMS. 2863 01:46:03,640 --> 01:46:06,560 SO I THINK THAT WHAT BOB'S 2864 01:46:06,560 --> 01:46:09,840 QUESTION MAY BE GETTING AT IS, 2865 01:46:09,840 --> 01:46:11,800 ARE THERE SORT OF ON A LARGER, 2866 01:46:11,800 --> 01:46:14,000 MORE BROAD LEVEL IS, ARE THERE 2867 01:46:14,000 --> 01:46:16,480 THINGS THAT WE CAN LEARN FROM 2868 01:46:16,480 --> 01:46:18,680 STUDYING BIOLOGICAL NEURAL 2869 01:46:18,680 --> 01:46:20,400 NETWORKS THAT WILL GIVE US SOME 2870 01:46:20,400 --> 01:46:22,120 CLUES ABOUT HOW WE CAN MAKE 2871 01:46:22,120 --> 01:46:25,080 ARTIFICIAL NEURAL NETWORKS MORE 2872 01:46:25,080 --> 01:46:26,400 EFFICIENT AND EFFICIENCY, I 2873 01:46:26,400 --> 01:46:28,760 THINK, IS KEY, AND I THINK THE 2874 01:46:28,760 --> 01:46:31,040 ANSWER IS PROBABLY YES. 2875 01:46:31,040 --> 01:46:33,440 BUT WE DON'T KNOW YET WHAT 2876 01:46:33,440 --> 01:46:37,200 THAT'S GOING TO BE. 2877 01:46:37,200 --> 01:46:39,080 >>SOMEWHAT ALIGNED TO THAT IS 2878 01:46:39,080 --> 01:46:43,120 ANOTHER QUESTION THAT HAS TO DO 2879 01:46:43,120 --> 01:46:46,400 WITH, ON ONE HAND, WHAT DO YOU 2880 01:46:46,400 --> 01:46:50,160 THINK OF THE IMPACT OF THE 2881 01:46:50,160 --> 01:46:54,040 UPCOMING QUANTUM PARTICULARLY 2882 01:46:54,040 --> 01:46:58,000 NOT JUST QUANTUM BIOLOGY AND 2883 01:46:58,000 --> 01:47:05,120 MECHANICS BUT OTHER ASPECTS OF 2884 01:47:05,120 --> 01:47:09,440 QUANTUM BIOLOGY GOING BACK TO 2885 01:47:09,440 --> 01:47:13,440 THE CONCEPT OF PHYSICISTS THAT 2886 01:47:13,440 --> 01:47:17,600 SPACE IS SORT OF ALMOST A MENTAL 2887 01:47:17,600 --> 01:47:18,760 CONSTRUCT THAT MAKES OUR 2888 01:47:18,760 --> 01:47:20,680 SURROUNDING REALITIES 2889 01:47:20,680 --> 01:47:21,240 UNDERSTANDABLE. 2890 01:47:21,240 --> 01:47:23,680 SO THE QUESTION THAT BOB ASKED 2891 01:47:23,680 --> 01:47:29,400 IS, DO NEUROSCIENTISTS USE THESE 2892 01:47:29,400 --> 01:47:30,920 KIND OF IMPLICATIONS IN TRYING 2893 01:47:30,920 --> 01:47:31,920 TO UNDERSTAND HOW THE BRAIN 2894 01:47:31,920 --> 01:47:36,040 CONSTRUCTS THE WORLD AROUND US? 2895 01:47:36,040 --> 01:47:38,440 AND I ADDED THE QUANTUM ASPECT 2896 01:47:38,440 --> 01:47:40,680 TO IT, BECAUSE THAT'S SOMETHING 2897 01:47:40,680 --> 01:47:44,200 THAT IS RAPIDLY EVOLVING AND TO 2898 01:47:44,200 --> 01:47:47,080 WHAT EXTENT HAS THAT IMPACTED 2899 01:47:47,080 --> 01:47:50,000 NEUROSCIENCE? 2900 01:47:50,000 --> 01:47:53,120 >>YEAH, I MEAN, PERSONALLY I 2901 01:47:53,120 --> 01:47:55,760 DON'T THINK QUANTUM PHYSICS HAS 2902 01:47:55,760 --> 01:47:57,720 HAD MUCH OF AN IMPACT ON 2903 01:47:57,720 --> 01:47:58,680 NEUROSCIENCE AT ALL. 2904 01:47:58,680 --> 01:47:59,960 MAYBE THERE'S SOMETHING THAT I'M 2905 01:47:59,960 --> 01:48:02,600 NOT AWARE. 2906 01:48:02,600 --> 01:48:05,800 I DO THINK THE QUESTION IS 2907 01:48:05,800 --> 01:48:07,400 INTERESTING ABOUT WHETHER, YOU 2908 01:48:07,400 --> 01:48:10,800 KNOW, SPACE IS REAL OR IF IT'S A 2909 01:48:10,800 --> 01:48:12,520 MENTAL CONSTRUCT, VERY DIFFICULT 2910 01:48:12,520 --> 01:48:15,560 QUESTION TO ANSWER, I THINK, BUT 2911 01:48:15,560 --> 01:48:19,880 I DO DEFINITELY THINK THAT, YOU 2912 01:48:19,880 --> 01:48:22,200 KNOW, WE FORM -- ONE OF THE 2913 01:48:22,200 --> 01:48:26,160 MAJOR THINGS THAT THE BRAIN DOES 2914 01:48:26,160 --> 01:48:28,120 IS IT FORMS AN INTERNAL MODEL OF 2915 01:48:28,120 --> 01:48:28,720 THE WORLD. 2916 01:48:28,720 --> 01:48:30,680 THAT'S WHAT OUR EXPERIENCES AND 2917 01:48:30,680 --> 01:48:33,040 OUR MEMORIES DO, IS THEY PRODUCE 2918 01:48:33,040 --> 01:48:34,000 AN INTERNAL MODEL OF THE WORLD 2919 01:48:34,000 --> 01:48:35,360 THAT ALLOWS US TO MAKE 2920 01:48:35,360 --> 01:48:35,640 PREDICTIONS. 2921 01:48:35,640 --> 01:48:39,680 IF I TRY TO JUMP FROM ONE ROCK 2922 01:48:39,680 --> 01:48:41,000 TO ANOTHER ROCK, I'M PRETTY SURE 2923 01:48:41,000 --> 01:48:42,520 I CAN MAKE IT, YOU KNOW, BECAUSE 2924 01:48:42,520 --> 01:48:44,360 I HAVE THIS MODEL OF HOW FAR I 2925 01:48:44,360 --> 01:48:47,840 CAN JUMP AND HOW BIG THAT GAP IS 2926 01:48:47,840 --> 01:48:48,960 AND WHETHER I'M GOING TO MAKE IT 2927 01:48:48,960 --> 01:48:50,000 OVER THERE OR WHETHER I'M NOT 2928 01:48:50,000 --> 01:48:51,080 GOING TO MAKE IT AND I'M GOING 2929 01:48:51,080 --> 01:48:51,960 TO FALL TO MY DEATH. 2930 01:48:51,960 --> 01:48:53,280 I MEAN, WE HAVE TO MAKE THOSE 2931 01:48:53,280 --> 01:48:56,240 KINDS OF PREDICTIONS ALL THE 2932 01:48:56,240 --> 01:48:57,480 TIME, AND WE WOULDN'T BE ABLE TO 2933 01:48:57,480 --> 01:48:59,080 DO THAT IF WE DIDN'T HAVE A 2934 01:48:59,080 --> 01:48:59,960 MENTAL MODEL OF THE WORLD THAT 2935 01:48:59,960 --> 01:49:02,720 WAS BUILT UP FROM OUR OWN 2936 01:49:02,720 --> 01:49:05,000 EXPERIENCES. 2937 01:49:05,000 --> 01:49:07,120 AND THAT MENTAL MODEL OF THE 2938 01:49:07,120 --> 01:49:09,880 WORLD STRONGLY INFLUENCES HOW WE 2939 01:49:09,880 --> 01:49:12,200 PERCEIVE EVERYTHING AROUND US. 2940 01:49:12,200 --> 01:49:13,600 WE'RE NOT SIMPLE MACHINES THAT 2941 01:49:13,600 --> 01:49:15,680 ARE JUST, LIKE, MEASURING THE 2942 01:49:15,680 --> 01:49:17,480 WAVELENGTH OF LIGHT THAT'S 2943 01:49:17,480 --> 01:49:18,680 COMING FROM THE PLANTS OUTSIDE 2944 01:49:18,680 --> 01:49:19,440 MY WINDOW. 2945 01:49:19,440 --> 01:49:21,720 YOU KNOW, WE'RE INTERPRETING 2946 01:49:21,720 --> 01:49:24,120 THOSE COLORS IN THE CONTEXT OF 2947 01:49:24,120 --> 01:49:26,280 THE SHAPE AND THE SHADING AND 2948 01:49:26,280 --> 01:49:27,400 THE OTHER THINGS AROUND THEM TO 2949 01:49:27,400 --> 01:49:28,880 KNOW THAT IT'S A PLANT AND NOT 2950 01:49:28,880 --> 01:49:32,720 JUST A GREEN THING. 2951 01:49:32,720 --> 01:49:34,480 SO WHAT'S REALITY, WHAT'S NOT 2952 01:49:34,480 --> 01:49:35,320 REALITY, THAT'S A HARD QUESTION 2953 01:49:35,320 --> 01:49:37,920 TO ANSWER, BUT THERE'S NO DOUBT 2954 01:49:37,920 --> 01:49:39,680 THAT EVERYTHING WE PERCEIVE IS 2955 01:49:39,680 --> 01:49:40,960 INFLUENCED BY OUR PAST 2956 01:49:40,960 --> 01:49:43,600 EXPERIENCES AND OUR INTERNAL 2957 01:49:43,600 --> 01:49:45,640 MODELS OF THE WORLD. 2958 01:49:45,640 --> 01:49:47,040 >>MARCUS, DO YOU WANT TO 2959 01:49:47,040 --> 01:49:47,600 COMMENT ABOUT THAT? 2960 01:49:47,600 --> 01:49:51,080 >>ALL I CAN THINK ABOUT WAS A 2961 01:49:51,080 --> 01:49:52,800 ONE-PAGER I WROTE FOR SCIENCE 2962 01:49:52,800 --> 01:49:56,760 SEVERAL YEARS AGO CALLED THE 2963 01:49:56,760 --> 01:49:58,240 BRAIN'S DARK ENERGY. 2964 01:49:58,240 --> 01:50:01,320 IN OTHER WORDS -- AND THE 2965 01:50:01,320 --> 01:50:02,960 RESPONSE TO THAT -- I GOT AN 2966 01:50:02,960 --> 01:50:05,240 EMAIL AND I'M -- I THINK I 2967 01:50:05,240 --> 01:50:10,160 STEPPED ON A PHYSICIST'S FOOT OR 2968 01:50:10,160 --> 01:50:11,440 SOMETHING OR TOE AND I GOT THIS 2969 01:50:11,440 --> 01:50:15,720 EMAIL THAT SAID -- HE SAID, DARK 2970 01:50:15,720 --> 01:50:19,680 MATTER, JEEEEEZ, LIKE, STAY OUT 2971 01:50:19,680 --> 01:50:20,160 OF THERE. 2972 01:50:20,160 --> 01:50:23,640 BUT WHEN YOU THINK ABOUT IT, YOU 2973 01:50:23,640 --> 01:50:26,440 KNOW, THE BRAIN IS DEVOTING AN 2974 01:50:26,440 --> 01:50:28,520 ENORMOUS AMOUNT OF RELATIVE 2975 01:50:28,520 --> 01:50:33,680 ENERGY TO ITS ONGOING STATE THAT 2976 01:50:33,680 --> 01:50:36,480 DIRECTLY HAS NOTHING TO DO WITH 2977 01:50:36,480 --> 01:50:37,760 MY MOVEMENT OF MY HAND OR MY 2978 01:50:37,760 --> 01:50:39,120 SPEAKING TO YOU, BUT PROVIDES 2979 01:50:39,120 --> 01:50:41,160 THE CONTEXT IN WHICH THAT IS 2980 01:50:41,160 --> 01:50:44,080 OCCURRING. 2981 01:50:44,080 --> 01:50:45,040 WHICH IN ORDER TO ACHIEVE WHAT 2982 01:50:45,040 --> 01:50:46,920 NELSON JUST TALKED ABOUT IS A 2983 01:50:46,920 --> 01:50:48,520 VERY EXPENSIVE BUSINESS OF 2984 01:50:48,520 --> 01:50:51,480 HAVING SOMETHING THAT HAS THIS 2985 01:50:51,480 --> 01:50:53,320 MODEL OF THE WORLD THAT IS 2986 01:50:53,320 --> 01:50:55,240 FLEXIBLE, ADAPTABLE AND 2987 01:50:55,240 --> 01:50:57,440 APPLIABLE, AND IT DOES SO AT 2988 01:50:57,440 --> 01:50:59,080 GREAT EXPENSE TO MAINTAIN IT 2989 01:50:59,080 --> 01:51:02,120 PROPERLY AND ADJUST IT ON THE 2990 01:51:02,120 --> 01:51:03,720 RUN. 2991 01:51:03,720 --> 01:51:04,400 ONLINE. 2992 01:51:04,400 --> 01:51:06,480 SOMETHING LIKE THAT. 2993 01:51:06,480 --> 01:51:07,560 AND THAT ACCOUNTS FOR WHAT I 2994 01:51:07,560 --> 01:51:10,320 WOULD CALL THE BRAIN'S DARK 2995 01:51:10,320 --> 01:51:11,160 ENERGY. 2996 01:51:11,160 --> 01:51:17,400 SO THAT'S A LITTLE PHYSICS. 2997 01:51:17,400 --> 01:51:22,160 >>ARE MEMORIES -- DO EITHER OF 2998 01:51:22,160 --> 01:51:24,600 YOU HAVE -- WE HAVE A QUESTION 2999 01:51:24,600 --> 01:51:26,320 HERE, WHY MEMORIES DURING 3000 01:51:26,320 --> 01:51:30,600 CHILDHOOD O -- ARE LONGER LASTIG 3001 01:51:30,600 --> 01:51:33,040 THAN MEMORIES IN ADULTHOOD? 3002 01:51:33,040 --> 01:51:35,560 DO WE HAVE ANY IDEAS ABOUT THAT, 3003 01:51:35,560 --> 01:51:35,800 MARCUS? 3004 01:51:35,800 --> 01:51:38,920 THAT MAY BE -- ARE THERE ANY 3005 01:51:38,920 --> 01:51:39,760 STUDIES, MAYBE WE CAN PUT THIS 3006 01:51:39,760 --> 01:51:41,200 IN A BROADER CONTEXT. 3007 01:51:41,200 --> 01:51:46,240 COULD YOU BRIEFLY SUMMARIZE THE 3008 01:51:46,240 --> 01:51:51,760 STATUS OF IMAGING APPROACHES TO 3009 01:51:51,760 --> 01:51:54,600 UNDERSTANDING OR PREDICTING 3010 01:51:54,600 --> 01:52:01,400 NEURODEGENERATIVE DISEASES, 3011 01:52:01,400 --> 01:52:03,440 INTELLIGENCE, ALL SORT OF 3012 01:52:03,440 --> 01:52:05,720 BEHAVIORAL TYPE OF THINGS, DO 3013 01:52:05,720 --> 01:52:09,040 PEOPLE WHO CAN MEMORIZE A POEM 3014 01:52:09,040 --> 01:52:15,240 BUT CAN'T MEMORIZE THE MUSIC OF 3015 01:52:15,240 --> 01:52:17,640 A CONCERT OR REVERSE, ARE THOSE 3016 01:52:17,640 --> 01:52:19,360 DIFFERENCES THAT YOU CAN DETECT 3017 01:52:19,360 --> 01:52:22,760 BY IMAGING? 3018 01:52:22,760 --> 01:52:24,160 >>I DON'T THINK I CAN ANSWER 3019 01:52:24,160 --> 01:52:26,880 THAT QUESTION DIRECTLY, BUT AS 3020 01:52:26,880 --> 01:52:30,400 OUR BRAIN AGES -- WELL, FIRST 3021 01:52:30,400 --> 01:52:33,840 OFF, IF YOU LOOK AT THE BRAIN 3022 01:52:33,840 --> 01:52:34,800 METABOLICALLY, IT'S NOT UNIFORM 3023 01:52:34,800 --> 01:52:36,200 TO BEGIN WITH. 3024 01:52:36,200 --> 01:52:38,600 AND ONE OF THE THINGS THAT HAS 3025 01:52:38,600 --> 01:52:41,240 GREATLY INTERESTED US OVER THE 3026 01:52:41,240 --> 01:52:44,400 YEARS WHEN WE CAME ACROSS THIS 3027 01:52:44,400 --> 01:52:47,760 IDEA THAT GLYCOLYSIS WHICH ONLY 3028 01:52:47,760 --> 01:52:50,160 PRODUCES A SMALL AATP, SO TO 3029 01:52:50,160 --> 01:52:51,800 SPEAK, BUT IT DOES IT IN A 3030 01:52:51,800 --> 01:52:56,760 VARIETY OF IMPORTANT WAYS, IS 3031 01:52:56,760 --> 01:52:57,560 NOT UNIFORM THROUGHOUT THE 3032 01:52:57,560 --> 01:52:57,760 BRAIN. 3033 01:52:57,760 --> 01:53:02,560 AND IN FACT, IT IS QUITE 3034 01:53:02,560 --> 01:53:05,120 SPECIFICALLY DEVOTED TO AREAS 3035 01:53:05,120 --> 01:53:12,200 THAT GENETICALLY ARE FOCUSED ON 3036 01:53:12,200 --> 01:53:13,280 NEONATUS GENES, IN OTHER WORDS 3037 01:53:13,280 --> 01:53:14,920 THINGS INVOLVED IN SYNAPTIC 3038 01:53:14,920 --> 01:53:15,960 PLASTICITY. 3039 01:53:15,960 --> 01:53:19,480 NOW GIVEN THAT RELATIONSHIP, 3040 01:53:19,480 --> 01:53:21,240 THIS HAS ALL BEEN PUBLISHED IF 3041 01:53:21,240 --> 01:53:22,320 SOMEBODY IS INTERESTED, BUT 3042 01:53:22,320 --> 01:53:23,800 WHAT'S VERY INTERESTING IS, AS 3043 01:53:23,800 --> 01:53:27,960 WE AGE, THIS DIFFERENCE IN 3044 01:53:27,960 --> 01:53:30,280 METABOLISM AND PARTICULARLY 3045 01:53:30,280 --> 01:53:31,760 AEROBIC GLYCOLYSIS DECREASES 3046 01:53:31,760 --> 01:53:34,840 WITH AGE. 3047 01:53:34,840 --> 01:53:36,560 NOW, LINKING THAT DIRECTLY TO 3048 01:53:36,560 --> 01:53:38,000 CHANGES IN SOMETHING LIKE MEMORY 3049 01:53:38,000 --> 01:53:40,920 HAS NOT BEEN DONE, BUT IF IT'S A 3050 01:53:40,920 --> 01:53:42,680 KEY TO THE GENETIC COMPOSITION 3051 01:53:42,680 --> 01:53:46,280 OF TISSUES THAT OBVIOUSLY HAVE 3052 01:53:46,280 --> 01:53:48,640 A DEGREE OF PLASTICITY THAT'S 3053 01:53:48,640 --> 01:53:50,520 DIFFERENT THAN OTHER AREAS, THIS 3054 01:53:50,520 --> 01:53:54,040 COULD EASILY HAVE AN EFFECT. 3055 01:53:54,040 --> 01:53:55,200 AND THE OTHER INTERESTING THING 3056 01:53:55,200 --> 01:53:57,920 IS THAT IT IS GENDER -- THERE IS 3057 01:53:57,920 --> 01:54:01,720 A GENDER DIFFERENCE AS TO 3058 01:54:01,720 --> 01:54:03,240 SECOND -- WE PUBLISHED A YEAR OR 3059 01:54:03,240 --> 01:54:06,200 TWO AGO, THAT WOMEN TEND TO 3060 01:54:06,200 --> 01:54:09,160 MAINTAIN THE AEROBIC GLYCOLYSIS 3061 01:54:09,160 --> 01:54:09,720 LONGER THAN MEN. 3062 01:54:09,720 --> 01:54:12,880 SO THE THREE OF US ARE DOOMED TO 3063 01:54:12,880 --> 01:54:14,040 BECOME MORE FORGETFUL THAN SOME 3064 01:54:14,040 --> 01:54:17,040 OF OUR FEMALE COMPANIONS. 3065 01:54:17,040 --> 01:54:17,640 MAYBE. 3066 01:54:17,640 --> 01:54:18,840 I DON'T KNOW. 3067 01:54:18,840 --> 01:54:20,800 BUT THE METABOLISM OF THIS AND 3068 01:54:20,800 --> 01:54:23,960 THE GENETICS BEHIND THE 3069 01:54:23,960 --> 01:54:25,600 METABOLISM DOES HAVE A LINK TO 3070 01:54:25,600 --> 01:54:29,080 THE MEMORY PROCESSES THEMSELVES, 3071 01:54:29,080 --> 01:54:32,480 AND OVER TIME, AND MAYBE 3072 01:54:32,480 --> 01:54:33,680 INDIVIDUALLY, THERE ARE 3073 01:54:33,680 --> 01:54:34,920 DIFFERENCES AS WELL. 3074 01:54:34,920 --> 01:54:36,240 BUT IT'S AN AVENUE THAT 3075 01:54:36,240 --> 01:54:43,360 CERTAINLY IS WORTH PURSUING. 3076 01:54:43,360 --> 01:54:46,600 >>WE HAVE A QUESTION ABOUT TWO 3077 01:54:46,600 --> 01:54:50,000 OTHER HUGE TOPICS. 3078 01:54:50,000 --> 01:54:54,680 ONE IS, WHAT DO YOU -- DO YOU 3079 01:54:54,680 --> 01:54:57,560 SEE A SIGNIFICANT IMPACT ON 3080 01:54:57,560 --> 01:55:00,160 ARTIFICIAL INTELLIGENCE ON THE 3081 01:55:00,160 --> 01:55:05,080 SYSTEMS THAT YOU BOTH WORK WITH, 3082 01:55:05,080 --> 01:55:09,200 AND THE OTHER IS, THERE SEEMS TO 3083 01:55:09,200 --> 01:55:14,240 BE INCREASING STUDIES LINKING 3084 01:55:14,240 --> 01:55:19,760 COMPUTER DRIVEN NEURAL FUNCTI 3085 01:55:19,760 --> 01:55:20,000 FUNCTIONS. 3086 01:55:20,000 --> 01:55:22,800 DO YOU WANT TO COMMENT ABOUT 3087 01:55:22,800 --> 01:55:26,280 EITHER OR BOTH OF THOSE FIELDS 3088 01:55:26,280 --> 01:55:29,440 WHICH ARE PRETTY NEBULOUS, I 3089 01:55:29,440 --> 01:55:31,920 AGREE, BUT YOU KNOW, IF WE'RE 3090 01:55:31,920 --> 01:55:39,200 SPECULATING A BIT, FEEL FREE. 3091 01:55:39,200 --> 01:55:40,920 >>MY LAB AND ME, WE ARE 3092 01:55:40,920 --> 01:55:41,640 ACTIVELY -- WE'RE VERY 3093 01:55:41,640 --> 01:55:43,040 INTERESTED IN ACTIVELY WORKING 3094 01:55:43,040 --> 01:55:45,360 ON UNDERSTANDING, YOU KNOW, THE 3095 01:55:45,360 --> 01:55:46,880 DIFFERENCES BETWEEN BIOLOGICAL 3096 01:55:46,880 --> 01:55:48,760 NETWORKS AND ARTIFICIAL 3097 01:55:48,760 --> 01:55:55,600 NETWORKS, AND I THINK THERE'S A 3098 01:55:55,600 --> 01:55:57,040 POTENTIAL THAT WHAT WE DISCOVER 3099 01:55:57,040 --> 01:55:58,600 AS BIOLOGISTS WILL HAVE 3100 01:55:58,600 --> 01:56:01,080 IMPLICATIONS FOR ARTIFICIAL 3101 01:56:01,080 --> 01:56:02,280 INTELLIGENCE. 3102 01:56:02,280 --> 01:56:04,360 IT'S ALSO TRUE THAT, YOU KNOW, 3103 01:56:04,360 --> 01:56:05,280 ARTIFICIAL INTELLIGENCE OR 3104 01:56:05,280 --> 01:56:07,960 MACHINE LEARNING HAS REALLY BEEN 3105 01:56:07,960 --> 01:56:10,240 ENABLING IN TERMS OF TRYING TO 3106 01:56:10,240 --> 01:56:12,840 UNDERSTAND LARGE DATASETS. 3107 01:56:12,840 --> 01:56:15,480 SO THERE'S A HUGE EMPHASIS IN 3108 01:56:15,480 --> 01:56:17,560 BIOLOGY THESE DAYS ON USING 3109 01:56:17,560 --> 01:56:21,240 MACHINE LEARNING TOOLS TO 3110 01:56:21,240 --> 01:56:22,560 CLASSIFY BEHAVIORS, FOR EXAMPLE, 3111 01:56:22,560 --> 01:56:24,200 TO RECOGNIZE PATTERNS IN THINGS 3112 01:56:24,200 --> 01:56:25,240 LIKE NEURAL ACTIVITY. 3113 01:56:25,240 --> 01:56:29,280 SO I THINK AS A TOOL, IT'S VERY 3114 01:56:29,280 --> 01:56:32,920 POWERFUL FOR BIOLOGISTS, AND 3115 01:56:32,920 --> 01:56:34,520 THEN AS A SYSTEM, A COMPLEX 3116 01:56:34,520 --> 01:56:36,680 SYSTEM THAT HAS AT LEAST SOME 3117 01:56:36,680 --> 01:56:38,480 PROPERTIES IN COMMON WITH 3118 01:56:38,480 --> 01:56:43,000 BIOLOGICAL NEURAL NETWORKS, THAT 3119 01:56:43,000 --> 01:56:44,040 COMPARISON THERE IS LIKELY, I 3120 01:56:44,040 --> 01:56:46,880 THINK, TO BE A VERY, VERY 3121 01:56:46,880 --> 01:56:47,840 IMPORTANT ONE. 3122 01:56:47,840 --> 01:56:51,840 AND FOR THAT REASON, I THINK WE 3123 01:56:51,840 --> 01:56:52,880 SEE BIOLOGY DEPARTMENTS AROUND 3124 01:56:52,880 --> 01:56:54,800 THE WORLD NOW INVESTING QUITE A 3125 01:56:54,800 --> 01:56:56,440 LOT IN HIRING PEOPLE THAT HAVE 3126 01:56:56,440 --> 01:56:59,040 THIS KIND OF EXPERTISE. 3127 01:56:59,040 --> 01:57:01,560 AND IT'S AN EXCITE TIME IN THAT 3128 01:57:01,560 --> 01:57:02,880 REGARD, AND WHO KNOWS WHAT'S 3129 01:57:02,880 --> 01:57:04,160 AROUND THE NEXT CORNER BECAUSE 3130 01:57:04,160 --> 01:57:06,560 THAT FIELD IS MOVING SO FAST, 3131 01:57:06,560 --> 01:57:11,080 IT'S ALMOST SCARY. 3132 01:57:11,080 --> 01:57:14,920 >>I GUESS I WOULD SECOND YOUR 3133 01:57:14,920 --> 01:57:16,480 ENTHUSIASM FOR SURE. 3134 01:57:16,480 --> 01:57:17,600 BECAUSE THE DATA THAT WE'RE 3135 01:57:17,600 --> 01:57:19,200 DEALING WITH, AND I TALKED ABOUT 3136 01:57:19,200 --> 01:57:21,160 IT IN A FAIRLY SIMPLISTIC WAY, 3137 01:57:21,160 --> 01:57:22,720 BUT WHETHER YOU GET INTO THESE 3138 01:57:22,720 --> 01:57:25,880 SYSTEMS AND YOU HAVE NEURAL 3139 01:57:25,880 --> 01:57:27,000 MODULATORS AND YOU HAVE ALL 3140 01:57:27,000 --> 01:57:27,840 THESE DIFFERENT CELL TYPES AND 3141 01:57:27,840 --> 01:57:28,960 ALL THESE DIFFERENCES IN 3142 01:57:28,960 --> 01:57:30,480 METABOLISM AND SO FORTH, AND HOW 3143 01:57:30,480 --> 01:57:34,280 YOU BEGIN TO SYNTHESIZE THAT 3144 01:57:34,280 --> 01:57:36,040 FROM THE DATASETS, IS A 3145 01:57:36,040 --> 01:57:37,600 CHALLENGE TO BEGIN WITH. 3146 01:57:37,600 --> 01:57:40,040 AND THE OTHER THING IS THAT IT'S 3147 01:57:40,040 --> 01:57:41,800 BECOME VERY APPARENT THAT FOR US 3148 01:57:41,800 --> 01:57:44,680 TO USE OUR DATA, PARTICULARLY AT 3149 01:57:44,680 --> 01:57:45,840 AN INDIVIDUAL LEVEL, WE NEED A 3150 01:57:45,840 --> 01:57:46,520 LOT OF IT. 3151 01:57:46,520 --> 01:57:48,600 SO YOU GET THESE MASSIVE 3152 01:57:48,600 --> 01:57:52,040 DATASETS WITH ALL THIS MATERIAL 3153 01:57:52,040 --> 01:57:55,600 IN IT, AND HAVING MORE 3154 01:57:55,600 --> 01:57:58,320 SOPHISTICATED CONCEPTS FROM A 3155 01:57:58,320 --> 01:58:00,960 SYSTEMS LEVEL, AND ALSO THE 3156 01:58:00,960 --> 01:58:02,360 TOOLS THAT -- COMPUTATIONAL 3157 01:58:02,360 --> 01:58:03,440 TOOLS THAT WOULD ALLOW US TO 3158 01:58:03,440 --> 01:58:06,040 LOOK FOR INCREDIBLY SUBTLE 3159 01:58:06,040 --> 01:58:06,720 DIFFERENCES. 3160 01:58:06,720 --> 01:58:09,080 I MEAN, FOR EXAMPLE, THERE WAS A 3161 01:58:09,080 --> 01:58:12,240 STUDY I WAS BRIEFLY INVOLVES IN 3162 01:58:12,240 --> 01:58:14,800 IN THE MCARTHUR NETWORK ON 3163 01:58:14,800 --> 01:58:16,440 NEUROSCIENCE IN THE COURTROOM. 3164 01:58:16,440 --> 01:58:18,120 AND THE REASON I ENDED UP ON 3165 01:58:18,120 --> 01:58:20,440 THIS PANEL WAS THE FACT THAT 3166 01:58:20,440 --> 01:58:22,920 IMAGING IS ENDING UP IN COURT 3167 01:58:22,920 --> 01:58:23,120 CASES. 3168 01:58:23,120 --> 01:58:24,520 PEOPLE WILL SHOW IMAGES AND THEY 3169 01:58:24,520 --> 01:58:27,440 SAY, WELL, HE DID IT BECAUSE OF 3170 01:58:27,440 --> 01:58:28,840 WHATEVER, BECAUSE HIS BRAIN 3171 01:58:28,840 --> 01:58:30,480 WASN'T WORKING RIGHT. 3172 01:58:30,480 --> 01:58:34,520 AND WE HAD THE OPPORTUNITY 3173 01:58:34,520 --> 01:58:39,120 THERE, THIS GROUP, TO LOOK AT 3174 01:58:39,120 --> 01:58:42,360 DATA OBTAINED IN THE NEW MEXICO 3175 01:58:42,360 --> 01:58:45,160 PRISON SYSTEM ON INCARCERATED 3176 01:58:45,160 --> 01:58:49,680 JUVENILES, AND SO THE COMMITTEE 3177 01:58:49,680 --> 01:58:51,480 AS WE DISCUSSED IT AND I SAID 3178 01:58:51,480 --> 01:58:52,800 WELL FOR PETE'S SAKE, YOU'VE GOT 3179 01:58:52,800 --> 01:58:54,080 TO GET RESTING STATE DATA. 3180 01:58:54,080 --> 01:58:55,680 LET'S JUST LOOK AT THE BRAIN AS 3181 01:58:55,680 --> 01:58:58,360 IT'S SITTING THERE. 3182 01:58:58,360 --> 01:59:00,320 SO THIS WAS DONE, AND ALSO THERE 3183 01:59:00,320 --> 01:59:02,960 WERE DETAILED BEHAVIORAL 3184 01:59:02,960 --> 01:59:04,920 STUDIES. 3185 01:59:04,920 --> 01:59:06,760 AND THE BIGGEST QUESTION ON THE 3186 01:59:06,760 --> 01:59:09,480 TABLE WAS IMPULSIVITY. 3187 01:59:09,480 --> 01:59:12,440 SO WE HAD JUST DEVELOPED AN 3188 01:59:12,440 --> 01:59:13,760 ALGORITHM FOR ANALYZING CERTAIN 3189 01:59:13,760 --> 01:59:15,280 ASPECTS OF DATA, AND I WON'T 3190 01:59:15,280 --> 01:59:17,120 BURDEN YOU WITH THE DETAILS OF 3191 01:59:17,120 --> 01:59:19,640 IT, BUT WE POSED A QUESTION OF 3192 01:59:19,640 --> 01:59:22,880 THIS RATHER LARGE -- IT WAS 107 3193 01:59:22,880 --> 01:59:24,080 JUVENILES HERE THAT HAD 3194 01:59:24,080 --> 01:59:26,720 DIFFERENT LEVELS OF IMPULSIVITY 3195 01:59:26,720 --> 01:59:28,680 BASED ON STANDARD WAYS OF 3196 01:59:28,680 --> 01:59:30,840 MEASURING THAT, AND WHAT WAS SO 3197 01:59:30,840 --> 01:59:32,360 STUNNING ABOUT IT WAS THE 3198 01:59:32,360 --> 01:59:34,720 RESULTS THAT CAME OUT OF IT AND 3199 01:59:34,720 --> 01:59:37,080 HOW SPECIFIC THEY WERE AND HOW 3200 01:59:37,080 --> 01:59:38,920 SPECIFIC THEY COULD BE 3201 01:59:38,920 --> 01:59:39,200 PREDICTIVE. 3202 01:59:39,200 --> 01:59:41,560 SO YOU TAKE 107 PEOPLE AND YOU 3203 01:59:41,560 --> 01:59:42,600 TAKE ONE PERSON OUT AND YOU 3204 01:59:42,600 --> 01:59:44,680 RECOMPUTE THE MODEL AND THEN YOU 3205 01:59:44,680 --> 01:59:46,200 CAN PREDICT WITH INCREDIBLE 3206 01:59:46,200 --> 01:59:47,000 ACCURACY. 3207 01:59:47,000 --> 01:59:48,960 SO WHAT DID WE FIND? 3208 01:59:48,960 --> 01:59:53,960 IT WAS A SUBTLE DIFFERENCE 3209 01:59:53,960 --> 01:59:55,600 BETWEEN TWO NETWORKS IN THE 3210 01:59:55,600 --> 01:59:56,480 BRAIN, PARTICULARLY THE 3211 01:59:56,480 --> 02:00:00,960 OPPONENTS OF THESE CORRELATIONS 3212 02:00:00,960 --> 02:00:02,920 BUT IT WAS A VERY SUBTLE CHANGE 3213 02:00:02,920 --> 02:00:04,920 IN THE BALANCE BETWEEN NETWORKS. 3214 02:00:04,920 --> 02:00:07,120 AND WHILE YOU COULD ARGUE, WELL, 3215 02:00:07,120 --> 02:00:09,800 IS THAT -- HOW GOOD A STUDY WAS 3216 02:00:09,800 --> 02:00:10,760 THAT, 107, SOME PEOPLE THINK YOU 3217 02:00:10,760 --> 02:00:13,600 HAVE TO HAVE A THOUSAND PEOPLE 3218 02:00:13,600 --> 02:00:14,360 AND WHATEVER. 3219 02:00:14,360 --> 02:00:17,640 BUT IT SUGGESTED TO ME THAT AS 3220 02:00:17,640 --> 02:00:18,960 WE LOOK FOR THESE CRITICAL 3221 02:00:18,960 --> 02:00:20,400 DIFFERENCES IN HUMAN BEHAVIOR, 3222 02:00:20,400 --> 02:00:21,800 THEY'RE GOING TO AMOUNT TO, IN 3223 02:00:21,800 --> 02:00:24,200 SOME INSTANCES, VERY SUBTLE 3224 02:00:24,200 --> 02:00:25,960 DIFFERENCES BETWEEN THE 3225 02:00:25,960 --> 02:00:27,400 PROPERTIES OF DIFFERENT AREAS OF 3226 02:00:27,400 --> 02:00:32,280 THE BRAIN AS THEY INTERACT AS A 3227 02:00:32,280 --> 02:00:34,880 COMMUNITY. 3228 02:00:34,880 --> 02:00:36,640 AND I THINK HAVING COMPUTATIONAL 3229 02:00:36,640 --> 02:00:40,640 TOOLS THAT CAN GO IN AND EXPLORE 3230 02:00:40,640 --> 02:00:43,480 THIS, IT JUST STRIKES ME AS 3231 02:00:43,480 --> 02:00:51,240 ALMOST -- AS A BYSTANDER -- NO 3232 02:00:51,240 --> 02:00:51,920 ARTIFICIAL INTELLIGENCE GUIDE, 3233 02:00:51,920 --> 02:00:53,320 BUT WE'RE GOING TO NEED THOSE 3234 02:00:53,320 --> 02:00:54,560 KIND OF TOOLS TO BEGIN TO SORT 3235 02:00:54,560 --> 02:00:56,640 IT OUT, AND AS I LOOK AT THE 3236 02:00:56,640 --> 02:00:57,920 BEAUTIFUL PICTURES, NELSON, THAT 3237 02:00:57,920 --> 02:01:01,080 YOU HAD, THE COMPLEXITY OF THE 3238 02:01:01,080 --> 02:01:02,480 ISSUES THAT ARE INVOLVED HERE 3239 02:01:02,480 --> 02:01:04,920 ARE ALMOST OVERWHELMING, AS YOU 3240 02:01:04,920 --> 02:01:06,240 LOOK AT THESE POPULATIONS OF 3241 02:01:06,240 --> 02:01:10,880 CELLS AND HOW DO YOU PULL OUT 3242 02:01:10,880 --> 02:01:12,520 THAT TREND IN THERE SOME WAY. 3243 02:01:12,520 --> 02:01:13,640 BUT THE OTHER THING THAT 3244 02:01:13,640 --> 02:01:15,080 PROBABLY OUGHT TO COME TO THE 3245 02:01:15,080 --> 02:01:17,760 FOREFRONT HERE IS, HOW WE 3246 02:01:17,760 --> 02:01:19,440 STIMULATE THE BRAIN NOW, THE USE 3247 02:01:19,440 --> 02:01:22,720 OF THINGS LIKE TRANSCRANIAL 3248 02:01:22,720 --> 02:01:24,520 MAGNETIC STIMULATION, HOW ARE WE 3249 02:01:24,520 --> 02:01:26,080 AFFECTING THESE SUBTLE 3250 02:01:26,080 --> 02:01:27,080 DIFFERENCES IN THE WAY THE WHOLE 3251 02:01:27,080 --> 02:01:28,840 SYSTEM IS BALANCED, AND I THINK 3252 02:01:28,840 --> 02:01:30,800 WE'RE HEADED IN A DIRECTION THAT 3253 02:01:30,800 --> 02:01:33,400 IS REALLY EXCITING AS WE THINK 3254 02:01:33,400 --> 02:01:35,240 ABOUT IT, BUT UNDERSTANDING WHAT 3255 02:01:35,240 --> 02:01:37,240 WE'RE ACTUALLY DOING IS GOING TO 3256 02:01:37,240 --> 02:01:40,320 BE ABSOLUTELY CRITICAL TO THIS. 3257 02:01:40,320 --> 02:01:43,560 ANYWAY, ENOUGH RAMBLING. 3258 02:01:43,560 --> 02:01:47,360 >>I REGRET THAT WE HAVE HIT OUR 3259 02:01:47,360 --> 02:01:51,880 TIME LIMIT WITH THE HOURS AT THE 3260 02:01:51,880 --> 02:01:52,960 NIH. 3261 02:01:52,960 --> 02:01:58,000 SO LISTEN, PERMIT ME ON BEHALF, 3262 02:01:58,000 --> 02:02:01,480 I'M SURE OF THE HUNDREDS IF NOT 3263 02:02:01,480 --> 02:02:02,800 THOUSANDS OF PEOPLE WHO ENJOYED 3264 02:02:02,800 --> 02:02:07,240 THIS PRESENTATION AND YOUR 3265 02:02:07,240 --> 02:02:11,520 DISCUSSION OF THE STATE OF THE 3266 02:02:11,520 --> 02:02:12,840 ART AND THE INCREDIBLE 3267 02:02:12,840 --> 02:02:17,760 EXCITEMENT THAT THE FUTURE PO 3268 02:02:17,760 --> 02:02:18,680 PORTENDS, AND THE GREAT 3269 02:02:18,680 --> 02:02:19,600 OPPORTUNITIES FOR YOUNG PEOPLE 3270 02:02:19,600 --> 02:02:23,520 WHO ARE INTERESTED IN THIS HUGE 3271 02:02:23,520 --> 02:02:25,600 PROBLEM OF HOW THE BRAIN WORKS. 3272 02:02:25,600 --> 02:02:27,480 ON BEHALF OF EVERYONE, WE WANT 3273 02:02:27,480 --> 02:02:30,560 TO THANK YOU FOR TAKING YOUR 3274 02:02:30,560 --> 02:02:35,200 TIME AND PARTICIPATING. 3275 02:02:35,200 --> 02:02:37,400 IF THERE ARE ANY ADDITIONAL LATE 3276 02:02:37,400 --> 02:02:38,280 QUESTIONS, WE'LL SEND THEM OFF 3277 02:02:38,280 --> 02:02:42,080 TO YOU AND IF POSSIBLE, YOU MAY 3278 02:02:42,080 --> 02:02:44,280 CHOOSE TO ANSWER. 3279 02:02:44,280 --> 02:02:46,920 BUT THANK YOU, THANK YOU VERY 3280 02:02:46,920 --> 02:02:48,680 MUCH, AND WE ALL LOOK FORWARD 3281 02:02:48,680 --> 02:02:52,120 THAT WE MAY HAVE ANOTHER SESSION 3282 02:02:52,120 --> 02:02:53,120 IN 10 YEARS TO CATCH UP. 3283 02:02:53,120 --> 02:02:54,240 THANK YOU. 3284 02:02:54,240 --> 00:00:00,000 >>YOU'RE WELCOME.