>> SO GOOD AFTERNOON EVERYBODY. WELCOME TO TODAY'S NEUROSCIENCE SEMINAR. IT'S MY PLEASURE TO INTRODUCE TODAY'S SPEAKER, ADRIAN OWEN. HE RECEIVED HIS Ph.D. FROM THE UNIVERSITY OF ONTARIO. ADRIAN RETURNED TO THE UK FROM 1997 TO 2010 HE SERVED AS THE ASSISTANT DIRECTOR OF THE MRC BRAIN SCIENCES UNIT IN CAME BRIDGE. COUPLE OF YEARS AGO IN TWEBT 10 HE MOVED TO UNIVERSITY OF WESTERNON TARIO WHEN HE HOLDS THE CANADA EXCELLENCE RESEARCH CHAIR IN COGNITIVE NEUROSENTENCE AND IMAGING. NOW, THROUGHOUT HIS CAREER, ADRIAN HAS PRODUCED A SUBSTANTIAL BODY OF REALLY EXCELLENT WORK ON FRONTAL STRIATUANDATTAL MECHANISMS OF WORKING MEMORY, PLANNING AND ATTENTION. IN ADDITION HOWEVER, IN THE LATE 1990S ADRIAN AND HIS COLLEAGUES BEGAN TO PUBLISH ON A DIFFERENT TOPIC, SPECIFICALLY THE POSSIBILITY OF RESIDUAL COGNITIVE FUNCTION NOTHING PATIENTS SOON TO BE IN PERSISTENT VEGETATIVE STATES. RELYING ON FUNCTIONAL BRAIN IMAGES THIS WORK PRODUCED A SERIES OF REMARKABLE DISCOVERIES ON THE INNER WORLD AND MENTAL LIFE OF THESE PATIENTS. IT'S CHANGED OUR VIEW OF THE VEGETATE OF STATE WHILE PROVIDING NOVARTIS ILLEGALS INSIGHT INTO OUR UNDERSTANDING OF AWARENESS AND CNESS. IT'S A STORY THAT AT TIME SYSTEM DISTURBING BUT IT'S ALWAYS FASCINATING AND OF MAJOR CLINICAL IMPORTANCE. SO WITH THOSE THOUGHTS IN MIND, PLEASE JOIN ME IN WELCOMING ADRIAN OWEN. [ APPLAUSE ] >> THANK YOU VERY MUCH ALLEX AND THANKS VERY MUCH FOR THE INVITATION TO COME SPEAK HERE. SO I'M GOING TO START BY ASKING TO YOU THINK ABOUT A QUESTION AND HOW CAN WE POSSIBLY KNOW THAT ANOTHER HUMAN BEING IS CONSCIOUS AND AWARE? WHEN I POSE THAT QUESTION, I'M NOT TRYING TO DIG MYSELF INTO AN IMMEDIATE PHILOSOPHICAL HOLE ABOUT THE NATURE OF CONSCIOUSNESS, I'M INTERESTED IN A MUCH MORE DOWN TO EARTH PRAGMATIC ISSUE, HOW COULD YOU KNOW, SAY THE PERSON SITTING NEXT TO YOU IS AWARE, AND BY AWARENESS, I MEAN, HOW CAN YOU KNOW THEY'RE AWARE OF WHO THEY ARE, WHERE THEY ARE, WHAT THEY DID YESTERDAY, AND PERHAPS WHAT THEIR PLANS ARE FOR TOMORROW. AND THE ANSWER TO THAT QUESTION IS IT'S IMPOSSIBLE UNLESS THAT PERSON IS BOTH WILLING AND ABLE TO TELL YOU. A MUCH EASIER QUESTION FOR SOMEONE TO TELL YOU IS WHETHER THAT PERSON NEXT TO YOU IS AWAKE. THERE ARE REALLY ONLY 2 THINGS WE CAN MEASURE THAT AWARENESS AND THERE'S WAKEFULNESS. THINK ABOUT WHAT HAPPENS TO YOU, IF YOU HAVE A GENERAL ANESTHETIC, YOU START TO FALL ASLEEP, YOU START TO LOSE WAKEFULNESS BUT YOU ALSO START TO CEASE TO BE AWARE OF WHERE YOU ARE IN THE PREDICAMENT THAT YOU ARE IN. WAIT FOR AWARENESS. THERE'S DIFFERENT COMPONENTS OF CONSCIOUSNESS. I'LL SHOW NUCLEOTIDES MANY CONTEXT THEY ARE SIS ASSOCIATIAATIVE. WAKEFULNESS IS PRETTY EASY TO ASSESS. YOU DON'T LOOK AT THE PERSON NEXT TO YOU, YOU ARE OPEN, IF YOU WANT TO GET SCIENTIFIC ABOUT TYOU COULD USE SOMETHING LIKE EEG AND YOU COULD PASSIVELY RECORD THE ELECTRICAL SIGNALS COMING FROM THE BRAIN AND YOU COULD DETERMINE THAT A PARTICIPANT IS AWEAK WITHOUT THEM HAVING TO INVOLVE THEMSELVES IN ANY OBVIOUS WAY IN THE EXPERIMENT THAT YOU ARE CONDUCTING. BUT AWARENESS ISN'T LIKE THAT. YOU CAN'T LOOK AT SOMEBODY AND KNOW THAT THEY ARE AWARE, BASED ON THEIR APPEARANCE. YOU CAN'T PUT ON A MEASURE AND A PASSIVE EG RESPONSE THAT'S INDICATIVE OF AWARENESS AT LEAST NOT IN MOST CONTEXT. SO HOW DO WE SOLVE THIS PROBLEM. HOW DO YOU DETERMINE SOMEBODY'S AWARE. THE ANSWER IS YOU'VE GOT TO DO IT BY INVITING THEM TO PARTICIPATE IN SOME SORT OF INTERACTION. YOU HAVE TO ELISSITY A RESPONSE FROM THEM. ESSENTIALLY THEY HAVE TO TELL YOU THAT THEY ARE AWARE AND THIS RESPONSE COULD TAKE THE FORM OF A RESPONSE, I SUPPOSE THAT WOULD BE MOST ADDITIONAL, THEY COULD BREAK AN ARM OR BLINK AN EYE, BUT IT'S THIS RESPONSE AND ONLY THIS RESPONSE THAT ALLOWS YOU TO CATEGORICALLY KNOW A PERSON IS AWARE. A QUICK DEMONSTRATION, WHAT I WILL REFER TO, I WILL COME BACK TO IT AT VARIOUS TIMES DURING MY TALK. SO I WANT EVERYBODY IN THE ROOM TO DO EXACTLY WHAT I'M ABOUT TO ASK YOU TO DO. IF YOU ARE CONSCIOUS, PLEASE RAISE YOUR LEFT ARM INTO THE AIR. GOOD. ALWAYS A RELIEVE--RELIEF WHEN YOU DO THAT. [LAUGHTER] IT'S COMMAND FOLLOWING, I ISSUED YOU A COMMAND AND YOU ALL DID EXACTLY WHAT I ASKED YOU TO DO AND ON THAT BASISS, I KNOW THAT YOU ARE AWARE. AND THAT'S ABSOLUTELY CENTRAL CLINICALLY PARTICULARLY TO US UNDERSTANDING OR BEING ABLE TO MEASURE THAT SOMEBODY IS AWARE. YOU HAVE TO ILLICIT THIS KIND OF RESPONSE. COMMAND FOLLOW SUGGEST ABSOLUTELY ESSENTIAL TO THAT. THIS IS A NEW IDEA AND THIS IS PERHAPS BEST ARTICULATION IN THIS SEMINOLE TEXT BY POSE IN SARCOMA, THEY SAID THE LIMIT OF CONSCIOUSNESS ARE HARD TO DEFINED SATISFACTORY WHICH IS ONLY FURTHER AWARENESS OF OTHERS BY THEIR APPEARANCE AND ACTS. YOU HAVE TO DO SOMETHING. YOU HAVE TO RESPOND. YOU HAVE TO ACT TO TELL ANOTHER HUMAN BEING THAT YOU ARE CONSCIOUS NOW, A LOT OF PEOPLE GET UPSET BY THIS NOTION AND WILL SAY THINGS TO ME LIKE, WELL I CAN MAKE A MACHINE THAT WILL RAISE ITS ARM. IT DOESN'T MAKE THE MACHINE CONSCIOUS AND THAT'S NOT REALLY THE QUESTION I'M INTERESTED IN. I'M NOT INTERESTED INDEED WHETHER WE CAN MAKE A MACHINE THAT CAN GIVE THE IMPRESSION THAT IT IS CONSCIOUS. I ASK THE QUESTION HOW DO WE THAN A HUMAN BEING IS CONSCIOUS OR AWARE AND I'M HOPING IF SOMEBODY CAN DEMONSTRATE YOU AND GENERATE A REQUIRED RESPONSE AND THEY ARE NECESSARILY 8 SO JUST PARK THAT THOUGHT FOR A MOMENT AND LET'S IN THE VEG STATIVE STATE. I'M NOT GOING TO SHOW YOU THIS VIDEO NOT BECAUSE THEY'RE FAMILIAR, VIDEO OF TERRY SHIVE O, I'M NOT SHOWING YOU THIS BECAUSE I WANT TO MAKE ANY SUGGESTIONS AS TO WHETHER SHE WAS CONSCIOUS OR COMCONSCIOUS, IT'S RELEVANT AT THE MOMENT. I'M SHOWING YOU THIS WITH THE DOMAIN AND INVADING ANYBODY'S ANYBODY'S--WITHOUT INVADING ANYBODY'S PRIEFACY. IT'S REFERRED TO AS A STATE OF WAKEFULNESS WITHOUT AWARENESS AND THAT'S BECAUSE THESE PATIENTS OFTEN HAVE SLEEPING AND WAKING CYCLES AS YOU'LL SEE HERE. THEY OFTEN OPEN THEIR EYES. THEY MIGHT APPEAR TO LOOK AROUND THE ROOM BUT THEY'LL NEVER FIXATE ON ANYTHING MEANINGFUL. NEVER FIXATE FOR MORE THAN A FLEETING MOMENT ON ANYTHING IN PARTICULAR. IT'S MADE ON THE ABSOLUTE LACK OF RESPONSIBILITY, YOU CANNOT ELISSITY A RESPONSE OF EXTERNAL SIMULATION, BEYOND BASIC REFLEXES. AND THIS IS THE BASIS UPON WHICH THE DESTRICKS WAKEFULNESS WITHOUT AWARENESS COMES FROM. THE ASSUMPTION THESE PATIENTS ARE UNAWARE. JUST IMAGINE THAT THIS PATIENT, YOU HAD A PATIENT, SO NOT THIS PATIENT, ANY PATIENT, YOU HAD A PARTICULAR LESION THAT RENDERED THEM INCAPABLE OF GENERATING ANY RESPONSES TO ANY EXTERNAL STIMULATION. WOULD IT NOT BE THE CASE THAT BASED ON WHAT I SAID, FIRST 5 MINUTES OR SO OF MY TALK ABOUT RESPONSIVITY BEING CRITICAL FOR DETECTING CNESS, WOULD IT NOT BE THE CASE THAT WE WOULD ASSUME THAT SUCH A PATIENT IS VEGETATIVE. A PATIENT COULDN'T GENERATE A RESPONSE. WE WOULD HAVE TO ASSUME THEY WERE VEGETATIVE BECAUSE THEY HAVE NO MECHANISM FOR TELLING US ANYTHING ELSE. SO, IF THE PATIENT WAS ACTUALLY C BUT JUST NONRESPONSIVE, I'M GOING TO ARGUE THAT WE WOULD NECESSARILY COME TO THE CONCLUSION THAT THEY WERE IN A VEGETATIVE STATE AND THAT'S THE QUESTION THAT'S PREOCCUPIED MOST OF WHAT I WILL TALK ABOUT TODAY. NOW THE REASON IS IT'S SUCH A DIFFICULT ISSUE, IS THE VEGETATIVE STATE IS A CONDITION THAT LIES IN AMONGST ALL SORTS OF THINGS THAT CAN HAPPEN TO YOU AFTER YOU HAD A VERY SEVERE BRAIN INJURY. MOST PEOPLE IN THIS SITUATION WILL GO THROUGH A PERIOD OF COMA. VEGETATIVE STATE AND COMA ARE OFTEN CONFUSED PARTICULARLY BY THE MEDIA. WE CAN ACTUALLY DISTINGUISH BETWEEN THE 2 CONDITIONS VERY EASILY BASED ON WAKEFULNESS. THAT FIRST COMPONENT OF CNESS. COMA PATIENTS TYPICALLY TO YOU OR I WOULD LOOK LIKE THEY'RARY SLEEP. THEY HAVE EYES CLOSED, THEY DON'T HAVE SLEEPING AND WAKING CYCLES. AS YOU'VE SEEN VEGETATIVE PATIENTS ARE SOMEWHAT ANIMATE, THEY OPEN THEIR EYES. ANOTHER CONFUSION THAT'S OFTEN MADE IS BETWEEN THE VEGETATIVE STATE IS BRAIN DEATH. THOSE 2 TERMS ALSO ARE OFTEN USED INTERCHANGEABLY IN THE MEDIA AND THEY'RE QUITE DIFFERENT CONDITIONS AND THAT'S PROBABLY BEST ILLUSTRATED BY LOOKING AT FTG OR GLUCOSE IMAGES OF THE BRAIN DEATH OF PARTICIPANTS, VERSES VEGETATIVE STATE AND IN BRAIN KEITH RESEE WHAT'S THE HOLLOW SKULL PHENOM NANOG AND THERE'S NO METABOLISM IN THE BRAIN OF A BRAIN DEATH PATIENT NORWILL THERE EVER BE. STATIVE STATE PATIENTS DON'T LOOK THE SAME, THEY DON'T LOOK LIKE THIS HOLLOW SKULL, YOU KNOW, BUT CLEARLY THEY--THEY ALSO ARE NOT ENTIRELY NORMAL EITHER, IT'S GENERALLY SUPPRESSED GLOBAL GROUP OR METABOLISM IN THE PATIENTS. -OF THAT THEY CAN MOVE, THE ARM, THE HAND THEY'RE ASKED TO RAISE MORE OFTEN THAN BY CHANCE BUT MAYBE NOT ALL THE TIME THEN THEY'LL BE CLASSED AS MINIMALLY CONSCIOUS. AND THIS IS--THIS DISTINCTION TO VEGETATIVE STATE IS EXTREMELY IMPORTANT, IT'S NOT JUST AN INTERESTING DIAGNOSTIC DISTINCTION, IT'S MEDICALLY AND LEGALLY EXTREMELY IMPORTANT BECAUSE MOST OF THE LEGAL CASES ABOUT END OF LIFE DECISION MAKING WHICH YOU WILL ALL BE AWARE OF REVOLVE AROUND THIS ISSUE OF WHETHER THE PATIENT HAD ANY AWARENESS. AND REALLY WHAT THAT MEAN SYSTEM WHAT SIDE OF THIS DISTINCTION, MINIMALLY CONSCIOUS VERSES VEG STATIVE. YOU MUST SHOW NO EVIDENCE OF ANY AWARENESS, IF YOU DO SHOW B YOU BECOME CONSCIOUS AND TO MY KNOWLEDGE, AT LEAST IN THE LONG-TERM PATIENTS THAT TYPICALLY ARE AT THE CENTER OF HIGH PROFILE MEDIA CASES, NONE OF THOSE CASES HAVE INVOLVE TED MINIMALLY CONSCIOUS PATIENTS, THEY ONLY INVOLVE PATIENT WHO IS APPEAR TO BE OR WHOM THE EVIDENCE IS THAT THEY ARE IN A VEG STATIVE STATE SO IT'S AN IMPORTANT DISTINCTION, BUT UNFORTUNATELY NOT 1 THAT WE CAN MAKE BASED ON ANY RESTING METABOLIC MEASURE, NOT 1 THAT I KNOW OF SO IF YOU LOOK AT AGAIN, THE GLUCOSE LEVELS, GLUCOSE METABOLISM IN THE MINIMALLY CONSCIOUS STATE AND IN THE VIG STATIVE STATE THIS, IS GROUP DATA, REALLY IT'S RATHER SIMILAR. SIMILARLY FOR COMA, I WILL DRAW YOUR ATTENTION TO GENERAL ANESTHESIA THERE BECAUSE THAT'S SOMETHING I WANT TO RETURN TO LATER ON IN MY TALK. MOST OF US IN THE ROOM HAD A GENERAL ANESTHETIC AT SOME POINT AND LUCKILY MOST OF US HAD RETURNED FROM THAT BUT YOU'LL SEE THE POINT DURING GENERAL ANALYSIS, AND DURING GLUCOSE, THAT METABOLISM IS RATHER SIMILAR TO THAT OF OF A VEGETATIVE OR MINIMALLY CONSCIOUS STATE PATIENT. AND OF COURSE, THE OTHER COMPARISON, THE REALLY SCARY 1, THE 1 MORE MOST UNCOMFORTABLE ABOUT IS THE VEG STATIVE STATE AND LOCKED IN SYNDROME. CLASSICALLY THERE IS NO OVERLAP HERE, THE LOCKED IN SYNDROME IS A WELL CHARACTERIZED CLINICAL CONDITION AND TYPICALLY, AGAIN, I'M SURE MANY OF YOU WILL KNOW, LOCKED IN SYNDROME, PATIENTS OFTEN CAN MOVE THEIR EYES OR CAN SIGNAL THAT THEY ARE AWARE. BUT WHAT ABOUT THE HYPOTHETICAL CASE OF A PATIENT WHO IS, COMPLETELY LOCKED IN, UNABLE TO SIGNAL THAT YOU'RE AWARE. NOT LOCKED IN SYNDROME IN THE CLINICAL SENSE BUT LOCKED IN THIS A SENSE THEY'RE ABLE TO SIGNATURES THAT WILL THEY'RE AWARE. I'M GOING TO ARGUE THERE ARE QUITE A FEW PATIENTS IN THIS CATEGORY WHO SEEM TO BE IN A VEG STATIVE STATE. SO AS ALEX SAID SAID IN HIS INTRODUCTION, I'VE BEEN WORKING ON THIS SINCE 1997 AND THE FIRST STUDIES WE CARRIED OUT IN VEGETATIVE PATIENTS THAT WERE DESIGNED TO SEE IF WE CHRONIC LIVER DISEASE ILLICIT ANY EVIDENCE OF RESIDUAL COGNITIVE FUNCTION BECAUSE THE OSUSMGZ UP UNTIL THAT POINT HAD ALWAYS BEEN THAT IF YOU DID FUNCTIONAL ACTIVATION STUDIES, YOU WOULD SEE NOTHING AND MOST OF OUR EARLY EXPERIMENTS INVOLVED PASSIVE STIMULATION OF VARIOUS KINDS, FACES, VARIOUS TYPES OF LANGUAGE TASKS SO I'LL JUST AS AN EXAMPLE, I'LL SHOW YOU WHAT HAPPENS WITH SPEED PROCESSING. HERE WE BORROWED STIMULI FROM JENNY AND JOHN IN CAME BRIDGE AND SORT OF--CAM BRIDGE AND MANY GROUP HIS CONDUCTED MANY EXPERIMENTS. AND IF YOU ULTIMATELY ALL KNOW YOU COMPARE SPEECH SENTENCES TO ACOUSTICALLY MATCHED, WE USE WHITE NOISE, THIS IS THE WHITE NOISE THAT HAS THE SAME SPECTRAL PROFILE. AND WHAT YOU SEE IS ACTIVITY IN A BILATERALLY IN A BROAD--A BROAD SET OF REGIONS INCLUDING THE [INDISCERNIBLE] AND THE SUPERIOR AND MIDDLE TEMPORAL REGION, I'LL GIVE A QUICK EXAMPLE OF THE CORS OF SPEC WE USE WITH OUR PATIENTS. >> RECORDING: THE DESSERT WAS PUT IN THE OVEN AT THE START OF THE MEAL. >> SO THE PATIENTS WILL HEAR THAT AND HEAR CORAALATEIVE NOISE AND COMPARING 1 WITH THE OTHER, WE'RE ABLE TO EXTRACT THE RESPONSE THAT IS SPECIFIC TO SPEECH OVER AND ABOVE THE BASIC RESPONSE TO SOUND. NOW WHAT WAS A SURPRISE IS THAT WHEN WE STARTED TO DO THIS IMPATIENCE, IT TURNED OUT TO BE EXTREMELY COMMON TO SEE NORMAL OR NEAR NORMAL RESPONSES IN PATIENTS WHO HAD BEEN DIAGNOSED AS ENTIRELY VEGETATIVE. IT TURNS OUT THAT ALMOST HALF OF THIS GROUP OF PATIENTS WILL PRODUCE ACTIVITY THAT IS SPECIFICALLY RELATED TO SPEECH AGAIN AS OVER AND ABOVE A GENERAL RESPONSE TO SOUND AND THIS RACES THE QUESTION, WELL, WHAT DOES THAT MEAN. THEY'RE RECEIVING SPEECH IN THE SENSE THEIR BRAINS ARE RESPONDING TO SPEECH BUT DOESN'T MEAN THEY HAVE ANY PHENOM NONAPOPTOTIC LAGEICAL EXPERIENCE IT DOES IT MEAN THEY UNDERSTAND SPEECH? THE ANSWER IS PROBABLY NOT AND WE KNOW THAT FROM A STUDY OF PROP FALL SEDATION WE CARRIED OUT WITH MATT DAVIS AND COLLEAGUES AT CAMBRIDGE A FEW YEARS AGO. WE TOOK A GROUP OF HEALTHY VOLUNTEERS, IT WAS A BIZARRE EXPERIMENT, OUR ETHICS COMMITTEE WOULD ONLY ALLOW US TO DO THIS WITH ANESTHESIOLOGISTS, SO THIS IS A GROUP OF RIGHT HANDED ANESTHESIOLOGISTS, WHETHER IT GENERALIZED TO THE REST OF THE POCHULATION, I DON'T KNOW BUT WE DID--WE PUT THEM THROUGH THE SAME EXPERIMENT, GAVE THEM THE SAME STIMULI YOU JUST WITNESSED, SPEECH VERSES CORRELATIVE NOISE AND PROP POLARIZED INDUCED SEDATION. IT'S A BIT OF A SURPRISE, SO THEY'RE AT THE TOP, FORTUNATELY THEY'RE RIGHT HANDED ANESTHESIOLOGYSTS DO HAVE A RESPONSE. SO THEY DO GENERATE THE CLASSIC SPEECH PATTERN. WHAT HAPPEN WHEN IS YOU DEDATE THEM THOUGH IS NOT VERY MUCH EVEN WHEN THEY'RE DEEPLY DEEDATED AND--SEDATED AND THEY'RE UNAWARE, THEY'RE HEAVILY SEDATED AND THERE'S NO SIGNIFICANT CHANGE IN THE SPEECH RESPONSE THEY--THE IS RATHER AWKWARD FOR PAIBTS WHERE YOU DON'T KNOW ABOUT THAT CONSCIOUSNESS. PATIENT WHO IS HAVE DISORDERS OF CNESS BECAUSE OF COURSE, IF OUR HEALTHY VOLUNTEERS WHEN THEY ARE UNCONSCIOUS OR UNAWARE ARE GENERATING RESPONSES TO SPEECH, THEN WE OF COURSE CANNOT ARGUE OR ASSUME THAT A VEG STATIVE PATIENT THAT PRODUCES ACTIVITY IN THIS AREA OR THEY'RE AWARE AT ALL. AND THIS IS TRUE FOR THE FUNCTIONAL STUDY IMAGES IN THIS AREA, TYPICALLY THEY INVOLVED STIMULATION OF A SORT THAT IS AUTOMATIC. SECH WAS ACTUALLY AUTOMATIC, YOU CAN'T DECIDE NOT TO PERCEIVE SPEECH, SOMETHING YOUR BRAIN DOES WHETHER YOU LIKE IT OR NOT. AND THIS IS REALLY THE THING THAT PUSHED US IN THE DIRECTION 5 YEARS AGO. WE MOVED IN AN ENTIRELY DIFFERENT DIRECTION TO TRY AND REPRODUCE SOME FORM OF COMMAND FOLLOWING IN ANY OF THESE PATIENTS. WE WENT BACK TO AN EXAMPLE, AND WE SET OUT TO TRY ASK PRODUCE EVIDENCE THAT SOME OF THESE PATIENTS COULD FOLLOW COMMAND. AS I ARGUED THAT IS FUNDAMENTAL TO UNDERSTANDING WHETHER SOMEBODY IS AWARE OR NOT. AND THAT'S BASICALLY AN FMRI EXPERTS I APOLOGIZE FOR THE CARTOON YOU'RE ABOUT TO WITNESS. IT HELPS ME TO MAKE POINTS TOO, FOR THOSE WHO MAY NOT BE EXPERTS. SO WHAT WE USE IS MOTOR IMAGERY. WE ASK PEOPLE TO IMAGINE THEY'RE PLAYING A GAME OF TENNIS, AND NOT BECAUSE WE'RE INTERESTED IN THE TENNIS AREA OF THE BRAIN OR WE THINK THERE IS 1. IT'S BECAUSE YOU WE DO THIS WITHOUT PRACTICE. THEY WILL DO SOMETHING LIKE THAT. AND IF YOU IMAGINE MAKING LARGE MOVEMENTS WITH 1 ARM OR BOTH ARMS. SEE SEE ACTIVITY WITH A BAND OF CORTEXS. IT CARRIES O. YOU CAN IMAGINE PLAYING TENNIS FOR MINUTES ON END AND THEY CAN KEEP DOING IT UNTIL YOU TELL THEM TO STOP AND WHEN THEY STOP, ACTIVITY IN THIS REGION DISAPPEARS. AND WE USE THIS AS A SIGNATURE OR MEASURE OF COMMAND FOLLOWING AND ABOUT--I'M ABOUT TO CONVINCE YOU THAT IT IS JUST AS RELIABLE AS ASKING SOMEBODY TO RAISE THEIR ARM TO INDICATE THAT THEY ARE CONSCIOUS. I WILL PREEMPT A QUESTION. WHEN I TALK ABOUT THIS DATA, SOMEBODY THROWS A HAND UP AT THE END OF THE TALK AND SAYS, WHY IMAGINE PLAYING TENNIS AND I WILL SHOW YOU 4 OR 5 SLIDES NOW THAT ADDRESS THAT ISSUE. WHY IT IS THAT WE CONTINUED WITH THIS PARTICULAR TASK, NOT USE WHATEVER YOUR FAVORITE FMRI TASK MAY BE WORKING MEMORY OR LANGUAGE COMPREHENS OR TARGET DETECTION, WHY IT IS WE START WITH GETTING PEOPLE TO IMAGINE PLAYING TENNIS. THE FIRST REASON IS THAT IT'S AMAZINGLY--IT'S ACTUALLY VERY STRAIGHT FORWARD. YOU DON'T NEED ANY STIMULI, YOU IMAGINE THEM PLAYING TENNIS AND THEY HAVE TO KNOW WHAT TENNIS IS, BUT IT REQUIRES NO INSTRUCTIONS. NO PARTICULAR DETAILS, AND YOU CAN IMAGINE THEM PLAYING TENNIS OR RELAX, AND ALSO IT GIVES EXAMLY ANATOMICALLY SPECIFIC RESULT SPECIALIZATION OF SPECIFIC ENDOTHELIAL WE CONDUCTED MANY, MANY, STUDIES USING THIS TASK NOW, THIS IS DATA COLLECTED JUST 2 WEEKS AGO AT WESTERN, THIS DATA WAS ENTIRELY UNMASKED. THESE ARE 30--THIS IS 5, 30 SECOND BLOCKS OF PLAYING TENNIS VERSES RELAXING. IT'S GROUP DATA. THIS IS WHAT YOU SEE IF YOU CAM POI IMAGINING PLAYING TENNIS TO RELAXING, IT'S ACTIVITY ONLY IN THE PREMOTOR CORTEX. THAT'S THE DIFFERENCE BETWEEN THOSE 2 CONDITIONS AT THE GROUP LEVEL. NOW OBVIOUSLY IF YOU LOOK AT INDIVIDUAL DAT AYOU SEE A SLIGHTLY DIFFERENT PATTERN. THESE ARE 12 PARTICIPANTS THIS, IS DATA DIRECT COLLECTED, AT THE UNIVERSITY OF WESTERNON TARIO, AND--WESTERN ONTARIO, THIS IS GROUP DATA, NO MORE THRESHOLD, NOT MASK INDEED ANY WAY, ALL OF THESE PARTICIPANTS ARE GENERATING ACTIVITY IN THE PRE-CORTEX. NOW OBVIOUSLY THERE IS A BIT OF VARIABILITY, SOME PARTICIPANTS ACTIVATE OTHER AREAS OF THE BRAIN AS WELL BUT IF YOU?0f]– LOOK AT THESE SIGNIFICANT BOXES, HOW MANY SUBJECTS OR HOW MANY OF THESE PARTICIPANTS ACTIVATE DIFFERENT REGIONS IN THE BRAIN THERE,'S CLEAR THERE'S THIS AREA OF COMMONNALLITY RIGHT ACROSS THE CORTESS'RE TEX AND IN THIS CASE, IT WAS IN THE LEFT HEMISPHERE AND MOST PEOPLE PLAY TENNIS OR IMAGINE PLAYING TENNIS WITH THE RIGHT HAND. SO THAT HAS NOT PARTICULARLY SURPRISING. THE OTHER REASON IS THAT YOU CAN DO IT VERY QUICKLY. SO THIS IS SOMETHING THAT WE NOW DO IT IN REALTIME WITH THE PATIENTS. WE PUT THE PATIENTS IN THE SCANNER OR IN THIS CASE HEALTHY VOLUNTEERS. WE ACQUIRE DATA FOR 5 MINUTES IN SIMPLE 30 SECOND BLOCK DESIGN. REST PLAY TENNIS. REST, PLAY TENNIS. YOU DON'T NEED TO DO 5 MINUTES. FROM THIS DATA WITHIN A COUPLE OF MINUTES IT'S CLEAR THAT THIS IS PARPAPTS RETURNING STATISTICALLY SIGNIFICANT RESULT AND VARIOUS POINTS DURING THE ACQUISITION AND AFTER 2 MIN ROUTES, 3-QUARTERS OF THE PARTIC PACTS ARE RETURNING, RESPONSE IN 3 MINUTES ALL OF THE MARK. THIS IS A MOVIE THAT'S GOING FASTER THAN REALTIME BUT THIS IS THE DATA TAKEN DIRECTLY OFF THE SCANNER. THESE ARE 30 SECOND EPOX, OF SOMEBODY RELAXING AND PLAYING REST--SORRY, RELAXING AND PLAYING TENNIS. HOPEFULLY THE BLUE LINE IS THE REASON OF INTEREST OVER THE SUPPLEMENTARY MOTOR AREA. HOPEFULLY IT'S CLEAR TO ALL OF YOU THAT YOU'RE GETTING A VERY STRONG RESPONSE IN THAT REGION EVEN AFTER 2 MINUTES OF SCANNING. THERE ARE MANY TASKS THAT MAY SEEM BETTER FOR MOTOR IMAGERY BUT WHEN YOU LOOK AT INDIVIDUAL SUBJECT DATA THEY'RE NOT RELIABLE AND FINDING A TASK THAT WORKS IN EVERY PERSON EVERY TIME IS REALLY ESSENTIAL FOR EVALUATING PATIENT DATA, IF YOU'RE GOING TO TRY AND DRAW A CONTROVERSIAL CONCLUSION, LIKE A VEG STATIVE PATIENT MIGHT NOT BE VEG STATE--VEGETATIVE AND MANY TASKS DON'T WORK THIS WELL. THESE ARE 1 OF MY FAVORITE AREAS AS YOU HEARD IN MY WORK IN MEMORY. WE ALL KNOW THAT THE PREFRONTAL CORTEX IS INVOLVED IN MEMORY AND IF YOU LOOK AT ACTIVITY IN THIS REGION, DURING A TOUGH WORKING MEMORY TASK, OVER THE SAME PERIOD, IN A SENSE IT'S NOT AS RELIABLE, AS A SINGLE CASE LEVEL AS IMAGINING PLAYING TENNIS AND IT GETS THERE IN THE END. EVERYBODY GENERATES PREFRONTAL ACTIVITY OF THIS GROUP, BUT IT TAKES 5 MINUTES TO GET THERE. NOW THIS, IS MY KEY SLIDE, REALLY. THIS IS WHY MOTOR IMAGERY IS THE ANSWER TO UNDERSTANDING COGNITION IN THIS PATIENT GROUP. AND IT'S ESSENTIALLY THAT THE GREAT THING ABOUT DOING SOMETHING LIKE IMAGINING PLAYING TENNIS IS THAT YOU DON'T HAVE TO DO IT. AND THEREFORE, IT IS A VERY GOOD INDICATOR THAT SOMEBODY RETAINS WILL OR VOLUNTEERSITION OR WHATEVER YOU--VOLITION. NOW YOU ALL RAISED YOUR ARM WHAT I ASKED YOU TO RAISE YOUR ARM. THE KEY THING IS NONE OF YOU HAD TO DO THAT, YOU ALL COULD MAKE A CHOICE NOT TO. AND WE KNOW BECAUSE SOME VERY DIFFICULT REVIEWERS MADE US DO THIS EXPERIMENT, WE KNOW PEOPLE CAN DO THE SAME THING WHEN THEY IMAGINE PLAYS TENNIS AND THIS IS THE MOST BIZARRE EXPERIMENT I EVER CONDUCTED AND THE THEY WERE ASKED TO IMAGINE PLAYING TENNIS AND THEY'RE TOLD TO IMAGINE PLAYS 10 XYST IN THE OTHER CONDITION THEY WERE ASKED TO NOT IMAGINE PLAYING TENNIS WHEN THEY WERE ASKED TO IMAGINE PLAYING TENNIS AND PEOPLE ARE VERY GOOD AT THAT. PEOPLE ARE EXTREMELY GOOD AT NOT IMAGINING PLAYING TENNIS WHEN THEY'RE ASKED TO PLAY TENNIS AND THEY'RE NOT BEING TOLD WHAT THEY'RE ASKED TO DO BECAUSE WE HAVE WILL. YOU CAN DECIDE NOT TO DO IT. IF I SAY TO YOU IMAGINE PLAYING TENNIS, IT IS NOT AN AUTOMATIC BRAIN RESPONSE TO GENERATE PREMOTOR ACTIVITY. AND WE CAN DO THIS IN ALL SORTS OF OTHER WAYS, TYPICALLY WE DON'T USE TERMS LIKE IMAGINE PLAYING TENNIS OR CUE PEOPLE WITH WORDS LIKE TENNIS AND EVEN SPEECH, THAT WHEN THE BEEP STARTS THE TALK AND YOU CAN SHOW THE SAME BEEP IN CONNECTICUT TEXT WILL GENERATE RELIABLE MOTOR ACTIVITY AND THIS IS REALLY JUST--REALLY THIS IS A SATISFY REVIEWERS, BUT, IT ISN'T REALLY TO MAKE THE POINT, THIS IS COMMAND FOLLOWING, THIS IS PEOPLE RESPONDING, DOING WHAT THEY'VE BEEN ASKED TO DO AND IN THIS CONTEXT, INDICATIVE OF AWARENESS. 1 MORE QUICK SLIDE, THIS IS DATA AGAIN, DAVID MEN DEN AND HIS CLEGS IN CAMBRIDGE, ASKED HIS PATIENTS TO IMAGINE PLAYING 10 AND I GUESS A LOT OF THAT PREMOTOR ACTIVITY STARTS TO FAIL TO MATERIALIZE, MODEL CITIZEN MODERATE SEICATION, YOU DON'T SEE IT AT ALL. --BUT AT LEAST FMRI DOESN'T RETURN EVIDENCE THAT THEY CAN. THAT WAS A VERY LONG PREAMBLE TO TRY TO ANTICIPATE SOME OF THE QUESTIONS THAT I'M LIKELY TO RECEIVE ABOUT THIS. I THINK NONE OF US WOULD HAVE BEEN--COULD HAVE BEEN CONFIDENT THAT THIS IS GOING TO WORK QUITE AS WELL, AS IT DID. THE VERY FIRST VEG STATIVE PATIENTS THAT WE EVER SCANNED AND ASKED TO IMAGINE PLAYING TENNIS IS THE PERSON I'M GOING TO TALK ABOUT RIGHT NOW. SHE WAS INVOLVED IN A VEHICLE ACCIDENT, SHE WAS A PEDESTRIANS HIT BY 2 CARS WHILE CROSSING THE ROAD AND THERE WAS NOTHING UNUSUAL ABOUT HER AS FAR AS HER CLINE CALIFORNIA DIAGNOSIS. WE SAW HER ABOUT 5 MONTHS AFTER HER ACCIDENT, UP UNTIL THAT TIME SHE HAD BEEN ASSESSED ON NUMEROUSŤ.Y[y OCCASIONS OCCASIONS AND SHE' D BEEN DIAGNOSES AND NEVER MADE ANY REFORM OF RESPONSE TO EXTERNAL FORM OF STIMULATION. WE DID THE SPEECH TASK I TOLD YOU ABOUT. SPEECH VERSES NOISE AND WE SAW PRETTY GOOD EVIDENCE OF ACTIVITY, EXACTLY WHERE WE WOULD EXPECT IT TO SEE AND WE WENT ON AND ASKED HER TO IMAGINE PLAYING TENNIS. WHEN WE DID THAT, SHE VERY RELIAISONNABLY GENERATED ACTIVITY IN HER PREMOTOR CORTEX IN AN AREA--IN EXACTLY THE SAME AREA AT THIS POINT WE'RE VERY FAMILIAR WITH SEE NOTHING HEALTHY VOLUNTEERS. NOW BEAR IN MIND, THIS WOMAN HAS MADE NO RESPONSES TO ANY FORM OF EXTERNAL STIMULATION. WE PUT HER IN THE SCANNER, ASKED HER TO IMAGINE PLAYING TENNIS, THEN RELAX, IMAGINE PLAYING TENNIS AND RELAX, AND THIS IS THE IMAGE THAT WE SAW. WE DID OTHER THINGS. WE ASKED HER TO DO OTHER THINGS AND NOT GOING TO BORE YOU R@ 2I]VM x„Y BREVITY, BUT THE MAIN OF THE TASK WAS SPACIAL IMAGERY, WE ASKED HER TO IMAGINE MOVING FROM ROOM TO ROOM IN HER HOUSE BECAUSE THIS GENERATES VERY RELIABLE ACTIVITY AND A WHOLE NETWORK OF THE AREA, PARTICULARLY, THE PLACE AREA, AS YOU ALL KNOW, POSTERIOR PARIETAL REGIONS AND A PREMOTOR CORTEX, IN HER CASE, SHE GENERATED SIGNIFICANT ACTIVITY IN ALL OF THOSE AREAS WHEN WE ASKED HER TO IMAGINE MOVING FROM ROOM TO ROOM IN HER HOUSE. NOW YOU MAY ARGUE AS PEOPLE DID, WELL, IT'S NOT EXACTLY THE SAME, SHE DOESN'T LOOK EXACTLY LIKE YOUR HEALTHY VOLUNTEERS, WELL SHE DOES LOOK LIKE HEALTHY VOLUNTEERS WITHIN THE BOUNDS OF THE NORMAL DISTRIBUTION OF FMRI RESPONSE THAT YOU SEE IN THE HEALTHY POPULATION AND YOU LOOK AT HER BOLD RESPONSE IN THE SUPPLEMENTARY MOTOR AREA AND THE FREE AREAS THAT ARE ACTIVATE INDEED THE SPACIAL NAVIGATION TASK, THERE IS IN ALL CASES THERE ARE AT LEAST 2 WALKING AND TALKING PEOPLE WHO GENERATE LESS ACTIVITY IN 1 OR MORE OF THOSE AREAS THAN SHE DOES. AND AGAIN, I WANT TO STRESS THAT UP UNTIL THIS POINT AND FOR A CONSIDERABLE PERIOD AFTER THIS SCAN, SHE MADE NO BEHAVIORIAL RESPONSES, NO CORROBRATIVE EVIDENCE THAT SHE WAS CONSCIOUS AT ALL RINGS OTHER THAN SHE COULD GENERATE THESE RESPONSES. I WOULD ARGUE, ALSO THAT HER TIME COURSES TELL US QUITE A LOT ABOUT THE LIKELIHOOD OF THIS BEING AN AUTOMATIC RESPONSE, IF YOU PULL OUT THE AVERAGE, THIS IS ACTIVITY IN THE SUPPLEMENTAL MOTOR AREA WHEN SHE'S PROMPTED WITH THE WORD TENNIS, PROMPTED WITH THE WORD REST AGAIN, WHAT'S I THINK REMARKABLE ABOUT THESE DATA IS THAT THE RESPONSE IS SUSTAINED, THIS ISN'T SOMETHING JUST HAPPENED AND GOES AWAY, WHEN WE ASK HER TO IMAGINE PLAYING TENNIS, SHE STARTED TO GENERATE THIS ACTIVITY IN THE PREMOTOR CORTEX, AND THAT ACTIVITY REMAINED UNTIL WE ASKED HER TO RELAX AND OF COURSE, IT'S SOMETHING THAT SHE WAS ABLE TO SWITCH ON AND OFF AT EVERY POINT THAT WE ASKED TO DO THIS AND THAT'S THE DATA THAT FEED INTO'S THIS STATISTICAL LEVERAGE THAT YOU'RE LOOKING AT HERE. NOW THE OTHER POTENTIAL THING WAS SOMETHING XREAMLY UNUSUAL ABOUT THIS WOMAN, SHE JUST HAPPENED TO BE IN CAMBRIDGE AT THE TIME. WE'RE WORK NOTHING CAMBRIDGE AND WE CAME CROSS THE 1 PERSON IN THE WORLD HERE WHO APPEARED TO BE VEGETATIVE BUT WASN'T, THAT TURNED OUT TO BE THE CASE NEITHER, OVER THE NEXT COUPLE OF YEARS WE SCANNED MANY PATIENTS WHO APPEARED TO BE ENTIRELY VEGETATIVE AND THESE ARE NOT PATIENTS FROM THE GENERAL POPULATION. WHERE I WAS WORKING AT THE TIME IN CAMBRIDGE, THERE WERE CLINICIANS AND LOTS OF EXPERIMENTS OF DIAGNOSING THESE CONDITIONS, THERE IS A 40-45% MISDIAGNOSIS RATE IN THE GENERAL POPULATION, THESE ARE PATIENT WHO IS HAD BEEN SEEN TIME AND TIME AGAIN OFTEN BY MULTIPLE TEAMS AND REPEATEDLY DIAGNOSED AS BEING UNAWARE AND VEGETATIVE. WHEN WE PUT THEM IN THE SCANNER, 20% OF THEM COULD RELIAISONNABLY GENERATE PATENTED ACTIVITY WITH THEIR BRAIN WHICH IS CLEARLY DEMONSTRATED OUR TASKS THAT THEY WERE NOT VEG STATIVE IN FACT. IN FACT I'M HAPPY TO ARGUE THAT I THINK THESE PEOPLE THAT I'M GOING TO FOCUS ON NOW, ARE ENTIRELY CONSCIOUS. NOW THE REASON I THINK THAT IS' THE CASE IS BECAUSE THEY DO EVERYTHING THAT THE REST OF US DO WHEN WE'RE IN A SCANNER AND OF COURSE WE DON'T KNOW WHAT THEY MIGHT NOT BE ABLE TO DO BUT IF YOU THINK ABOUT WHAT'S INVOLVED IN GENERATING ACTIVITY IN YOUR PREMOTOR CORTEX WHEN YOU IMAGINE PLAYING TENNIS, IT DRAWS ON ASPECTS OF LONGTERM MEMORY. YOU HAVE TO REMEMBER WHAT TENNIS IS, YOU WORKING MEMORY, YOU'VE GOT TO SUSTAIN THIS. IT'S A 30 MINUTE ACQUISITION PERIOD AND FMRI SCANNER AND LOT OF WORK AND MEMORY GOING ON, ATTENTION, ATTENTION SELECTION, SHE CAN MOVE THAT FIRST PATIENT I'VE SHOWN YOU CAN MOVE FROM 1 TASK TO THE OTHER AND PACK AGAIN. ALL OF THESE HIGH LEVEL COGNITIVE EXECUTIVE PROCESSES THAT WE TYPICALLY ASSOCIATE WITH NORMAL CONSCIOUSNESS, SHE CLEARLY HAD ALL OF THESE THINGS INTACT IN ORDER TO RETURN THIS PATTERN OF ACTIVITY AS DO THE 20% OF PATIENTS WHO APPEAR TO BE ENTIRELY VEGETATIVE BUT IN FACT CAN DO THIS. SO IT WAS A FAIRLY SMALL CONCEPTUAL JUMP FROM THERE TO MOVE TOWARDS TRYING TO COMMUNICATE WITH SOME OF THESE PEOPLE. AND THE PRINCIPLE WAS VERY SIMPLE. WE TOOK THE 2 TASKS THAT WE DESCRIBED DENNIS IMAGERY AND THE SPACIAL NAVIGATION TASK AND WE ASK THE PATIENTS TO DO THIS FOR 5 MINUTE PERIOD, FLIPPING BETWEEN REST AND THE IMAGE RETASK, AND REHAD THIS 10ATIVE IN THE PREMOTOR CORTEX WITH THE SPACIAL NAVIGATION, WE MOVE AROUND AROUND THE PARIETAL CORTEX AND WE USE THAT REASON OF INTEREST, WE THEN TELL THEM TO IMAGINE PLAYING TENNIS FOR AN ESSAY AND IMAGINE ROOMS, TO ROOM IN YOUR HOUSE AND THEN ASK QUESTIONS. THIS IS ANOTHER STAD CARRIED OUT BY 1 OF MY POST DOCS, HE ASKED THEM 3 QUESTIONS HE COULDN'T KNOW THE ANSWER TO LIKE HAVE YOU GOT ANY BROTHERS OR SISTERS AND HE SAID, I IMAGINE PLAYING TENNIS OR MOVE AROUND THE ROOMS OF THEIR HOME BY GENERATING A YES OR NO. AND GENERATING IT OUT OF THE SCANNER HE COULD TELL WITH RELIABILITY, 20 PEOPLE, 60 QUESTIONS HE GOT THE CORRECT YES AND NO ANSWER, IN HEALTHY VOLUNTEERS. SO THAT WORKS, THAT'S EASY. SO AGAIN WE DIDN'T ANTICIPATE HOW QUICKLY THIS WAS GOING TO WORK IN A PATIENT WHO APPEARED TO BE VEG STATIVE. SO THIS SAY PATIENT WHO WAS SCANNED BY STEVEN AND THIS GROUP AND IT CAME ALONG QUICKLY AFTER WE GOT THIS TECHNIQUE WORKED OUT. THIS WAS HIS LOCALIZED DATA DOWN HERE WHEN WE ASKED HIM TO IMAGINE PLAYING TENNIS, HIS ACTIVITY AND PREMOTOR CORTEX AND ASKED HIM TO IMAGINE MOVING ROOM TO ROOM IN HIS HOUSE, THIS IS HIS ACTIVITY. NOW HE'S GOT MASSIVELY ENLARGED VENTRICULAR SPACES. THIS PATIENT HAD BEEN ASSUMED TO BE IN A VEG STATIVE STATE FOR 5 YEARS, IT WAS A TRAUMATIC BRAIN INJURY. HE HAD BEEN IN A CAR ACCIDENT AND FOR 5 YEARS IT HAD BEEN ASSUME THAD HE WAS IN A VEG STATIVE STATE. YET WHEN HE WAS PUTTING IN THIS THE SCANNER HE COULD GENERATE THESE NOW CHARACTERISTIC PATTERNS OF FMRI ACTIVITY WHEN HE WAS ASKED TO IMAGINE PLAYING TENNIS AND MOVE ROOM TO ROOM IN HIS HOUSE. NOW OF COURSE QUITE DIFFICULT IN A PATIENT LIKE THIS, HIS BRAIN7H-j IS BEING SEVERELY DAMAGED TO BE ENTIRELY CONFIDENT THAT THIS IS AN AREA HERE THIS, IS A LATERAL FREE MOTOR AREA AND I WILL SHOW YOU THAT I DON'T THINK THAT MATTERS VERY MUCH BECAUSE OF COURSE, WE CAN USE THE LOCALIZE THE DATA TO GENERATE, ROIs AND IN THIS CASE, WE ASK HIM QUESTIONS. WE SAID, WELL, IMAGINE PLAYING TENNIS AND MOVING ROOM TO ROOM IN YOUR HOUSE, AND THIS IS THE LOCALIZED DATA YOU'RE LOOKING AT. THIS IS WHAT HAPPEN WIDE WE ASKED HIM, IS YOUR FATHER'S NAME THOMAS, SO THIS GATHERS A WHOLE LIST OF POTENTIAL NAMES. ALL INFORMATION WE DIDN'T 99 ADVANCE, OF COURSE THAT WAS IMPORTANT TO KEEP THE PROSPEEDURE ENTIRELY BLINDED. AND WHEN WE SAID IS YOUR FATHER'S NAME THOMAS THAT'S WHAT WE SAW. THIS IS WHY I DON'T THINK IT MATTERS WHETHER THIS IS HIS AREA OR NOT, THIS IS A COMPLETELY DIFFERENT TIME. THIS IS HIM IMAGINING AROUND MOVING IN THE HOUSE THIS, IS HIM ANSWERING THE QUESTION, IS YOUR FATHER'S NAME THOMAS AND HE KNOWS TO SAY NO, HE HAS TO IMAGINE MOVING AROUND ROOMS OF HIS HOUSE AND BEAR IN MIND--I THINK I FORGOT TO SAY THIS. THIS REQUIRES NO PRACTICE. THIS IS NOT SOMETHING WE TRAIN THD PERSON TO DO, THIS IS A PATIENT PUT INTO THE SCANNER AND ASKED TO DO THE 2 TASKS AND THEN TOLD THAT WE'LL KNOW IF HE'S COMMUNICATE FIGURE HE DOES 1 OF THESE 2 TASKS TO SAY YES OR NO. HOPEFULLY YOU'RE CONVINCED THAT HIS FATHER'S NAME WASN'T THOMAS, HIS FATHER'S NAME TURNED OUT TO BE ALEXANDER. HE ASKED 5 QUESTIONS IN A ROW LIKE THIS, WHEN WE ASKED HIM THE QUESTION, HE WOULD GENERATE EITHER TENNIS PLAYING FOR YES OR AT LEAST THE--FMRI RESPONSE WOULD BE ASSOCIATED WITH TENNIS, AND THEREFORE MY RESPONSE WOULD BE ASSOCIATE WIDE MOVING AROUND HIS HOUSE. CLEARLY THERE'S NO QUESTION THAT THIS PATIENT IS CONSCIOUS, CONSCIOUS AND COMMUNICATE NOTHING ANY NORMAL SENSE OF THAT WORD. HE'S CONVEYING INFORMATION THAT WE HAVE NO OTHER WAY OF KNOWING OTHER THAN BY READING HIS BRAIN ACTIVITY AND THIS IS AN ACT. IT'S NOT A PHYSICAL ACT, IT'S A BRAIN ACT. BUT IT'S AN ACT THAT IT TURNS OUT IT IS JUST AS RELIABLE AS HAD WE ASKED HIM TO RAISE--HAD HE BEEN PHYSICALLY ABLE--RAISE HIS RIGHT HAND AND AS I BEBAN MY TALK BY ARGUING WE BASED ALL ASSUMPTIONS BY SOMEBODY'S AWARENESS OR KUBS CONSCIOUSNESS BASED ON WHETHER THEY WOULD DO THAT AND I WOULD ARGUE THAT'S EVERY REASON TO CONCLUDE THAT THIS GENTLEMAN WAS NOT VEGETATIVE AT ALL, HE'S ENTIRELY CONSCIOUS AND AWARE OF WHAT IS GOING ON AROUND THEM. AND THE PREDICAMENT THEY'RE IN. IT DOESN'T MEAN THAT WE KNOW--JUST BECAUSE HE CAN ANSWER YES OR NO TO HIS FAMILY AND FRIENDS, OF COURSE IT DOESN'T MEAN THAT WE KNOW EVERYTHING ABOUT HIM, WE DON'T KNOW WHETHER HE'S HAPPY OR SAD EAR DEPRESSED OR WHETHER HE WANTS TO LIVE OR DIE BUT WE CAN--ALL THOSE QUESTIONS CAN BE ANSWERED WITH I YES AND A NO AND THEREFORE, WE CAN BEGIN TO UNPACK SOME OF THAT INFORMATION AND WORK OUT WHAT IT'S LIKE TO BE IN THIS SITUATION AND WHAT OTHER ASPECTS OF MORE COMPLEX COGNITIVE FUNCTION MAY OR MAY NOT BE INTACT AND I'LL FINISH BY GIVING YOU A TASTE OF SOME OF THE THINGS THAT WE ARE DOING NOW IN THIS PATIENT POPULATION. MANY THINGS THAT WE WANT TO KNOW ABOUT THEM AND WE'RE USING MANY DIFFERENT TYPES OF TASKS TO ACCESS ASPECTS OF THEIR PRESERVED5pw COGNITION. THIS AGAIN, THOSE OF YOU WHO MIGHT REMEMBER MY FORMER LIFE AS A FRONT AT LOBE GUY, THIS IS A TASK I LOVE, TARGET DETECTION, HAVING PEOPLE LISTEN TO A STREAM OF WORDS, SOME OF THE WORDS THAT ARE REPEATED AND IN SOME BLOCKS YOU ASK THE PARTICIPANTS TO SIMPLY COUNT THE WORDS OR EVEN JUST ATTEND TO THE WORDS AND OTHER BLOCKS YOU JUST SAY, RELAX AND LET THE WORDS WASH OVER YOU. AGAIN, MOUNTING 1 OF MY POST DOCS WAS ABLE TO SHOW EXTREMELY CONVINCING WORKING MEMORY PERFORMANCE. IN A PATIENT WHO ABSOLUTELY, YOU COULD NOT HAVE EXTRACT THD INFORMATION FROM THE PATIENT IN ANY SORT OF BEHAVIOR. THEY HAD NO WAY OF KNOWING THIS PATIENT COULD DO A WORKING MEMORY TEST AND I WOULD ARGUE THIS IS VERY GOOD EVIDENCE. IT'S OF COURSE VERY CLEAR THAT THIS PERSON IS DOING PRETTY MUCH WHAT THIS HEALTHY--HEALTHY PARTICIPANT IS DOING, ACTIVATING THE SAME AREA OF THE BRAIN AND THE SAME PERIODIC FLUCTIATIONS AND IN THIS SENSE WE'RE ABLE TO CONCLUDE THAT HIS WORKING MEMORY IS INTACT. THIS IS MORE IMPRESS AND I HAVE THIS IS NEW DATA. THIS IS FROM ADAM HALFSHIRE AND WORKS WITH ME AND BETH PARK AND A FORMER STUDENT OF MINE. THEY WANTED TO ASK THE QUESTION, WELL, CAN THESE PATIENTS REASON? WELL HERE'S SOMETHING THAT PEOPLE ASK ME ALL THE TIME BUZZ IF WE ARE GOING TO USE IN THE DIRECTION OF USING THIS TYPE OF APPROACH THORS ASK MUCH MORE THORNY QUESTIONS ABOUT PEOPLE'S FUTURES, YOU WANT KNOW MUCH MORE THAN THEY CAN JUST ANSWER YES OR NO QUESTIONS, YOU WANT TO START TO UNDERSTAND WHETHER THEY CAN REASON. DO THEY UNDERSTAND THE CONSEQUENCES OF THE DECISIONS THEY'RE MAKING, SOMEWHAT OF A DEPARTURE FROM THAT EXACT SCENARIO, BUT THIS IS JUST TO ESTABLISH THAT A PATIENT CAN REASON, AGAIN THIS IS--LOOKING DOWN HERE, VEG VEGETATIVE PATIENT WHO MADE NO EXTERNAL RESPONSES. THIS WAS EXACTLY LIKE THIS BUT IT'S A VERSION OF VERBAL REASONING TASK, WHEN YOU HEAR SOMETHING LIKE BA, THE DECISION YOU HAVE TO MAKE IS WHETHER A DOES NOT PROCEED B IS TRUE OR FALSE. HOPEFULLY YOU'RE ALL HAVING PROBLEMS WITH THAT BECAUSE IT'S REALLY HARD TO DO, IT'S A GOOD DURABLE REASONING TASK. IT CORRELATES HIGHLY WITH MOST PLEASURED FLUID INTELLIGENCE AND USING A VERSION OF THIS TASK ADAM AND FRIENDS HAVE MANAGED TO RELIAISONNABLY MANAGED TO DEMONSTRATE THEY ARE VEG STATIVE CAN GENERATE ACTIVITY TO INDICATE WHETHER THIS TYPE OF QUESTION,ww  IS TRUE AND ON THAT BASIS I WOULD ARGUE THIS PATIENT IS REASONING OR AT LEAST WE'RE MEASURING WITH THE ABILITY TO REASON. WITH NO BEHAVIORIAL OUTPUT, AT LEAST NO BEHAVIORIAL PHYSICAL OUTPUT, SIMPLY USING BRAIN ACTIVITY AS THE NEUROPSYCHOLOGICAL TOOL IF YOU LIKE TO EVALUATE THIS--THIS GENTLEMAN'S COGNITIVE STATUS. SO I'LL JUST END BY TELLING YOU WHERE WE WANT TO GO FROM NOW. THAT'S WHERE WE ARE. WHERE WE REALLY NEED TOO GET TO, IS HERE AND THAT IS TO DEVELOP A BRAIN, AN INTERFACE, SOMETHING THAT WILL ALLOW HE'S PATIENTS TO COMMUNICATE ON A MORE REGULAR BASIS. FMRI WORKS FANTASTIC FOR DETECTING PATIENTS WHO APPEAR TO BE UNCONSCIOUS BUT TURN OUT TO ACTUALLY BE CONSCIOUS. IT'S VANSLY NOT GOING TO BE SOMETHING YOU CAN TAKE HOME WITH THEM AND USED TO COMMUNICATE ON A DAY-TO-DAY BASIS. EEG POSSIBLY OFFERS THAT IN THE FUTURE. AND OF COURSE THERE ARE PLENTY OF VERY SMART BRAIN INTERFACE GUIDES AROUND DEVELOPING THINGS THAT CAN DO CLEVER TRICKS LIKE THIS, THIS IS A COLLEAGUE OF MINE, WHAT HE'S TRYING TO DO IS TO INFLUENCE A BALL OVER HERE AND HIT THE TARGET. THE BALL IS MOVING LEFT AND RIGHT AUTOMATICALLY BUT HE CAN MOVE THE BALL UP AND DOWN BY IMAGINING SQUEEZING HIS HANDS OR SQUEEZING HIS FEET. THAT'S A FAIRLY SOPHISTICATED BRAIN COMMUNICATIVE DEVICE BUT IF YOU CAN IMAGINE THERE WAS A YES UP HERE AND A NO DOWN HERE THEN THIS PERSON COULD ANSWER YES OR NO QUESTIONS AT A RATE OF EVERY ONCE EVERY 5 OR 6 SECONDS WHICH IS ONCE EVERY 5 OR 6 SECOND WHICH IS IS WHAT WE ACHIEVED RELIAISONNABLY IN MACS WITH FMRI. HE'S PRETTY ACCURATE. THIS IS A HEALTHY PARTICIPANT. PRETTY ACCURATE, BUT THIS REQUIRES TRAINING TREQUIRES TRAINING, HIM BEING TRAINED AND ALSO THE ALEGORITHMS BEING TRAINED TO DECODE THAT PATENT OF EEG RESPONSES AND THAT'S SOMETHING THAT'S REALLY HARD TO ACHIEVE IN THESE PATIENTS BEARING IN MIEBD THAT MOST OF THE TIME WE GO INTO THE SITUATION, WE DON'T EVEN KNOW WHETHER THE PATIENT IS CONSCIOUS, WHETHER WE'RE GOING TO BE ABLE TO TRAIN THEM TO USE THE BRAIN TO COMMUNICATE INTERFACE AND I THINK WE'RE MAKING HEAD WAY. THE END OF LAST YEAR, NOVEMBER, WE PUBLISHED A PAPER SHOWING THAT WE COULD DETECT CONSCIOUSNESS IN PATIENT WHO IS OTHERWISE APPEAR TO BE VEGETATIVE USING DESYNCHRONNIZATIONS USING EEG AND THAT WE HAD 16 VEGETATIVE PATIENTS IN THAT GROUP, WE ASKED THEM TO--AT LEAST MY POST DOC DOWN HERE ASKED THEM TO IMAGINE SQUEEZING THEIR RIGHT HAND OR IMAGINE SQUEEZING BOTH OF THEIR FEET, AND THEY WERE ABLE TO CLASSIFY SIGNIFICANTLY ABOUT CHANCE, THOSE RESPONSES, HAND SQUEEZING OR FEET SQUEEZING IN 3 OF 16 VEGETATIVE PATIENTS. AGAIN SOMETHING LIKE 20% OF THIS POPULATION OF PATIENTS THEY MANAGED TO CORRECTLY CLASSIFY AS AGAIN. AS COMMAND FOLLOWING. SO AGAIN, THIS IS NOT SOMETHING THAT COULD HAPPEN AUTOMATICALLY, AND THE PATIENT IS CUED WITH A BEAT. THEY TOLD HIM THE ADVANCED SET OF BEATS, A HAND SQUEEZE OR FOOT BEATS, IT'S THE SAME RESPONSE AND HOPEFULLY I CONVINCED YOU THAT THAT'S AS GOOD A MEASURE OF COMMAND FOLLOWING AND THEREFORE AWARENESS AS ANY OTHER. SO I'LL END BY COMING BACK TO THAT QUOTE THAT I LOVE. I LOVE IT REALLY BECAUSE OF THE TIMING, 1966, WHICH OLDSMOBILE IN FURTHER SELF-AWARENESS OF OTHERS AND BY THEIR APPEARANCE AND THEIR ACTS. CLEARLY BY THE TIME THIS COMMENT WAS MADE, IT WAS A LONG PERIOD BEFORE MOST OF THE BRAIN IMAGES TOOLS THAT WE ALL USED AT LEAST IN THEIR CURRENT CONTEXT WERE EVEN THOUGHT ABOUT, YET IN 1966, IN FACT, SOME YEARS BEFORE THE EXISTING DEFINITION OF A VEG VEGETATIVE STATE WAS EVEN LAID DOWN AND WHAT I LIKE ABOUT THIS IS THAT I KNOW THAT WHEN THEY'RE REFERRED, WHEN THEY'RE REFIRED TO ACTS, THEY MEANT PHYSICAL ACTS, THEY MEANT RAISING YOUR ARM OR PERHAPS LINKING AN EYE OR A VERBAL RESPONSE AND I THINK WE ARE AT A STAGE NOW THAT IN SOME CONSTRAINED CIRCUMSTANCES, AN ACT CAN BE JUST A BRAIN ACT, IT CAN BE JUST SOMETHING YOU DO WITH YOUR BRAIN AND HOPEFULLY I CONVINCED YOU THAT IN SOME CLINICAL CONTEXT, THAT COULD BE EXTREMELY USEFUL. I'LL TAKE QUESTIONS AND I WILL LEAVE MY MANY, MANY COLLABORATORS, LOTS AND LOTS OF CLEVER PEOPLE DEAL WITH THIS WORK. THIS IS NIGH GROUP AT UNIVERSITY OF WESTERN ONTARIO, AND THIS IS IN THE BRAINUMENT IN CAMBRIDGE UNIT. THIS IS 1 OF MY POTE DOCKS THAT'S GONE TO UCLA AND WE HAVE LONG COLLABORATIONS AND ALL THE PEOPLE THAT WORK IN BRAIN IMAGES SCAN MOST OF THE PARENTS THAT I DESCRIBED TODAY. THANKS FOR YOUR ATTENTION. [ APPLAUSE ] >> [INAUDIBLE QUESTION FROM AUDIENCE ] >> WELL, THAT RAISES INTERESTING QUESTIONS IN CASE YOU DIDN'T HEAR IT, IT WAS CAN WE USE THE FMRI RESPONSE TO--I FORGOTTEN,--SORRY? WE DON'T REALLY NEED IT FOR BRAIN DEAD, IF A PATIENT IS TRULY BRAIN DEAD THEN YOU CAN USE OTHER TYPES OF IMAGES TO ESTABLISH THAT THAT IS THE CASE. YOU REALLY NEED IT IN CASES WHERE THE PATIENT'S NOT BRAIN DEAD BUT THERE'S A QUESTION ABOUT RESIDUAL CONSCIOUSNESS AND THAT IS CENTRAL TO MANY, LONG-TERM LEGAL DECISIONS, MANY OF THE DECISION MAKING. MUCH OF THE DECISION MAKING ASSESSMENT AROUND WHETHER THEY'RE CONSCIOUS OR NOT CONSCIOUS. AND TOUCHINGOT SECOND COMMENT YOU MADE IT COULD BE USED IN THE FUTURE TO GET INFORMED CONSENT WITH A PATIENT. 1 WOULD WANT TO MAKE SURE THE VARIOUS PRECAUTIONS WERE PUT IN PLACE TO MAKE SURE THAT IT WAS USED APPROPRIATELY AND RELIAISONNABLY AND SO ON AND SO FORTH BUT THERE'S NO REASON WHY YOU COULDN'T EXTRACT CONSENT FROM A PATIENT FOR WHATEVER USING THIS TYPE OF A FUNCTION. SHOULD I GO TO THE PEOPLE OF THE MIKE ON ROUGH ATOM PHONE? SORRY, YOU WERE FIRST. >> SO YOU SAID ABOUT 20% OF THE VEGETATIVE PEOPLE YOU TESTED WERE ABLE TO RESPOND AND THEN YOU GO ON AND TALK ABOUT THE REASONING TEST AS L. SO I GUESS I'M WONDERING ARE THERE DIFFERENT LEVELS OR VARYING DEGREES OF THE PEOPLE WHO ARE ABLE TO RESPOND OR DO YOU THINK THAT EVERYBODY WHO CAN RESPOND CAN REASON? >> SO I DON'T KNOW THE ANSWER TO THAT QUESTION. I KNOW THINGS ARE MOVING ALONG VERY QUICKLY, WE ONLY REPORT TO THE FIRST PATIENT THAT WE COMMUNICATE TO IN 2010. SO, MY HUNCH IS THAT THEY CAN. I'M SURE THERE WILL BE VARIABILITY, THERE WILL BE DIFFERENCES IN WHAT 1 PATIENT CAN DO AND ANOTHER PATIENT, JUST AS THERE ARE BEHAVIORIAL DIFFERENCES. SOME PATIENT K'S CLEARLY COMMUNICATE QUITE OFTEN BY MOVING 1 ARM, SOME PATIENTS CAN'T COMMUNICATE AT ALL. SO I'M SURE THEY WILL THERE WILL BE VARIABILITY, WHAT WE TEND TO SEE IN THE IMAGE SYSTEM SOMEBODY CAN DO IT OR THEY CAN'T. SO THE RESPONDERS ARE PRETTY CLEAR CUT AND WE DON'T HAVE AN AWFUL LOT OF PEOPLE SORT OF IN THE MIDDLE WHERE WE THINK, ARE THEY RESPONDING OR AREN'T THEY. AT LEAST IN THOSE SITUATIONS WE JUST TEND TO HAVE TO CONCLUDE THAT WE DON'T KNOW WHAT THEY'RE DOING, BUT SOMEBODY HAS TO GENERATE--I MEAN THE STAKES ARE PRETTY HIGH HERE. THEY HAVE TO GENERATE A CONVINCING RESPONSE SO TYPICALLY PATIENT K'S DO IT OR THEY CAN'T. >> THANK YOU, VERY INTERESTING. >> SO, SEEMS LIKE HAVE YOU A NICE BINARY SYSTEM, 1 VERSES ANOTHER THAT YOU CAN DISTINGUISH AND I'M WONDER WHAT YOU THINK IS THIS MAY BE A QUESTION ABOUT THE KIND OF TIME COURSE IN WHICH THESE CHANGES HAPPEN, I'M WONDERING IF YOU CAN DO A MORSE CODE OR IFFkBQ6 YOU CAN DO, YOU KNOW THE BUTTERFLY, YOU READ LEADERS AND YOU GET A STOPPER OR CONTINUE TO SIGNAL. BUT IT SEEMS LIKE IT'S A 5 MINUTE ACQUISITION, SO YOU SEE THE GETTING THERE, DO YOU REALIZE THIS? >> WE TRIED ALL SORTS OF DIFFERENT THINGS, I'M SURE YOU CAN IMAGINE AND YOU KNOW, I DIDN'T HAVE TO TIME DESCRIBE EVERY DIFFERENT THING WE'VE TRIED BUT AS AN EXAMPLE, WE ACTUALLY SET OUT WITH 4 DIFFERENT RESPONSES, WE DIDN'T FOCUS ON MOTOR IMAGERY REVERSES, MOVING AROUND YOUR HOUSE, WE USE THINGS LIKE FOCAL REHEARSAL, IMAGINING FACES, WE HAD 4 CONDITIONS BECAUSE IT WAS THE--DIFFERENT TYPES OF RESPONSES, TURNS OUT EVEN IN THE NORMAL POPULATION, BEING IN THE MAGNET, HAVING TO GENERATE THIS TYPE OF IMAGERY, MORE POSSIBLE TASKS YOU HAVE TO CONSIDER. THE LESS RELIABLE YOUR RESPONSES ARE. THEY'RE JUGGLING 4 THINGS AROUND AND YOU'VE GOT TO DECIDE, IS THIS TENNIS OR HOUSE OR AM I SUPPOSED TO BE SINGING IN MY HEAD, EVERYTHING GETS A LITTLE BIT LESS RELIABLE, SO THE ANSWER ISN'T TO INCREASE THE NUMBER OF TASKS THAT'S NOT SOMETHING YOU WERE SUGGESTING. >> SO THE ANSWER IS TO TRY AND TURN THE OUTPUT INTO SOMETHING THAT IS MORE USEFUL OR IS MORE FLEXIBILITY AND I THINK EEG WILL ALLOW US TO DO THAT IF WE CAN GENERATE A BRAIN [INDISCERNIBLE] INTO PLACE THAT ACTUALLY WORKS IN PATIENTS WHO CANNOT GENERATE ANY PHYSICAL RESPONSE. WITH FMRI WE TRIED A FEW THINGS BUT THEY ACTUALLY--BECAUSE IT'S SO RELIABLE, THEY USUALLY ENDED UP GOING BACK TO A VERSION OF THE SAME THING SO CAN YOU GET THEM TO SPELL FOR EXAMPLE, BY GETTING THEM TO START IMAGINING PLAYING TENNIS WHEN THEY HEAR A PARTICULAR LETTER AND THEN STOP FROM PLAYING TENNIS WHEN THEY HEAR THAT LETTER AGAIN, IT'S EXTREMELY RUDIMENTARY AND SLOW. HOW YOU WOULD TURN IN SOMETHING LIKE--I GUESS MORSE CODE IS ANOTHER, IT'S INCREDIBLY COMPLICATED THOUGH. IF YOU TRY TO LEARN MORSE CODE. BUT IT MIGHT--IT MIGHT NOT BE SOMETHING VERY EASY FOR THESE PATIENTS TO DO. >> [INAUDIBLE QUESTION FROM AUDIENCE ] ACTUALLY AT THEM ABOUT THEIR EXPERIENCE-- >> ALL RIGHT, SO THE FIRST QUESTION REALLY IS, THE ANSWER IS OVER WHAT PERIOD YOU MEET. SO, I MEAN CERTAINLY THESE PATIENTS DO IT BECAUSE WE TELL THEM WE WANT TO IMAGINE PLAYING TENNIS WHEN THEY HEAR A KEY WORD AND WE MIGHT DO THAT 3 OR 4 TIMES DURING THE SCANNING SESSION AND WE DON'T HAVE TO REINSTRUCT THEM EVERY TIME SO IN SOME RELATIVELY SHORT-TERM SENSE, THEY LAID DOWN A NEW MEMORY. WE PROBABLILY WOULDN'T RISK BRINGING SOMEBODY BACK A WEEK LATER AND THEN NOT INSTRUCTING THEM AND HOPING THEY MIGHT DO IT BECAUSE QUITE A LOT OF NEWS AND IT DOESN'T WORK BUT WE CAN CERTAINLY TEST THAT AND PERHAPS WE SHOULD. >> SO RECOVERY IS VERY IMPORTANT ISSUE, IN FACT, I TOOK OUT A SLIDE--IT'S GONE BUT I TOOK OUT A SLIDE BEFORE I STARTED THIS TALK IN THE INTEREST OF TIME, WHEN YOU PLOT FMRI RESPONSES, THIS IS IN THE SOUND CONDITION, IF YOU PLOT WHERE PEOPLE WILL BE 6 MONTHS FROM NOW, THERE'S A REASONABLE CORRELATION BETWEEN THE HOW ELABORATE THEIR FMRI RESPONSES ARE WHEN THEY CAN RESPOND TO WHETHER IT'S SPEECH, OR JUST SOUND, THEY HAVE NO RESPONSES AT ALL. AND WHERE THEY WILL BE CLINICALLY 6 MONTHS FROM NOW SO IT HAS SOME PROGNOSTIC VALUE AND IT DOESN'T RECALL WHERE YOU ARE RIGHT NOW WHICH IS QUITE INTERESTING SO WE CAN'T TELL WHETHER YOU ARE WE CAN TELL WHETHER WE WERE HAVING THIS PROVED 6 MONTHS NOW CORRELATION SUGGESTED THE RELATIONSHIP THERE. AND IT'S ALSO THE CASE THAT THE FIRST PATIENT IMAGINE PLAYING TENNIS DID GO ON TO RECOVER, AND 11 WEEKS AFTER WE SAW HER SHE WAS ABLE TO--HE WAS MINIMALLY CONSCIOUS AND ABLE TOW GENERATE SOME PHYSICAL RESPONSE WITH HER BODY BUT OTHERWISE, IT'S ALL ANECDOTAL. >> I WAS WONDERING HOW WELL THEY RESPOND TO PAINFUL STIMULANTS [INDISCERNIBLE] WITH THE PATIENTS. >> YEAH, IT'S DIFFICULT, AND WE'VE--WELL, WE'VE NEVER BEEN ABLE TO--IT MIGHT SOUND--WE'VE NEVER BEEN ABLE TO DO THAT, PARTICULARLY IN CAMBRIDGE BECAUSE OUR ETHICS COMMUNITY WAS NOT COMFORTABLE ADMINISTERING PAIN. WHICH IS FINE, THERE IS A GROUP THAT HAS DONE IT IN BELGIUM, THEY HAVE DIFFERENT ETHICAL--STANDARDS, PROBABLY THE PRONG WORD. [LAUGHTER] HE'LL KILL ME FOR THAT I'M SURE. NO, HE HAS DONE IT. AND IT'S AN INTERESTING ILLUSTRATION, I THINK OF THE PROBLEMS TRYING TO INTERPRET FMRI, AND THEY'RE ILLICKITYING THE PAIN MATRIX AND IT'S A COMPLICATED WHETHER THEY ACTIVATE THEIR PAIN MECHANISM OR NOT. I BELIEVE MOST OF US THAT SOMEBODY CAN FEEL PAIN BASED ON WHETHER THERE'S ACTIVITY IN RESPONSE TO PAINFUL STIMULI. IT'S REALLY--YOU HAVE NO OTHER EVIDENCE TO BASE THAT ON. WE CAN ASK, AND IF THEY'RE IN PAIN--OF COURSE A LOT OF PAIN AND ENTIRELY SUBJECTIVE AND THAT WOULD WOULD SUGGEST IS WHAT WEWE SHOULD ASK ALL THESE QUESTIONS BECAUSE IT'S A BRILLIANT APPLICATION, THE TEAKNIQUE THAT ISN'T TERRIBLY ETHICALLY COMPLICATED, LIKE DO YOU WANT TO LIVE OR DIE? WHICH IS WHAT A LOT OF PEOPLE THINK WE ASK THESE PATES. ARE YOU COMP FORTABLE WITH PAIN. IT'S A LOW ETHICAL OVERHEAD. >> THE EXPERIMENTS WITH THE EEG MIGHT ADDRESS THESE IN CASE THERE'S STILL AN INTEREST IN THE FMRI, AND JUST SORT OF DOING IT, I'M WONDERING IF CONSIDERED USING MULTIVARIANT APPROACHES IS TELL YES OR NO BECAUSE I SUSPECT THESE FROM NORMAL DATA THAT YOU WOULD GET FAST TO RESPOND THEN WITH THE 30 SECONDS ON OR OFF AND THE ETHICS AND SO ON. >> YOU'RE DEFINITELY RIGHT. THAT'S SOMETHING WE SHOULD DO. YOU KNOW AGAIN 1 OF THE BEAUTIES OF THIS APPROACH OR 1 OF THE REASONS WE'VE STUCK WITH IT IS THAT IT IS VERY EASY AND IT JUST WORKS. AND I'M SURE IF WE COULD DO REALTIME IN BPA AND IF WE COULD IMPLEMENT THAT AND GET MORE ELABORATE RESPONSES, IT WOULD OBVIOUSLY BE A BETTER THING TO DO, I THINK I WOULD RATHER BE CONVINCED IT COULD RETURN A MORE RELIABLE RESPONSE AND A BLOCK DESIGNED TO RELAX AND PLAY TENNIS BEFORE HAND AND THE ADDRESS IT THE FIRST TIME WITH WE ARE STILL INTERESTED IN IT, RIGHT BECAUSE I'M NOT AN EEG GUY. AND IT'S BEEN REALLY DIFFICULT TO GET THE EEG WORKING ANYTHING LIKE AS WELL AS THE FMRI AND THAT'S PART OF THE ANATOMY OF COURSE AND THE PATIENT ANATOMY IS NOT GENERALLY AN ANATOMY AND YOUR AND MY ANATOMY AND THE TREMENDOUS POWER IN BEING ABLE TO SAY THAT'S WHERE THE ACTIVITY IS, AND IT DOESN'T MATTER EXACTLY WHICH BIT OF THE BRAIN IS IN THERE BUT IT'S IN EXACTLY THE SAME PLACE IN EVERY TRIAL SO FOR THE SAKE OF TIME, I'M STILL VERY MUCH FOCUSED ON IMPROVING FMRI AND HEARING MORE ABOUT THAT. >> THANK YOU. >> FANTASTIC! >> [ APPLAUSE ]