>> WELCOME, EVERYBODY, TO THE
29th MEETING OF THE BRAIN
MULTI-COUNCIL WORKING GROUP.
I'M SUSAN WEISS, THE DIRECTOR OF
THE DIVISION OF EXTRAMURAL
RESEARCH AT THE NATIONAL
INSTITUTE ON DRUG ABUSE, BUT I'M
HERE TODAY ACTING AS THE
DESIGNATED FEDERAL OFFICIAL FOR
THE BRAIN MULTI-COUNCIL WORKING
GROUP.
AS MOST OF YOU ALREADY KNOW, THE
MULTI-COUNCIL WORKING GROUP IS
NOT A FORMAL ADVISORY COMMITTEE
UNDER THE FEDERAL ADVISORY
COMMITTEE ACT.
RATHER, IT SERVES IN AN ADVISORY
CAPACITY TO THE TEN COUNCILS FR
BRAIN INSTITUTES AND CENTERS.
IT WAS ESTABLISHED BECAUSE IT
WAS RECOGNIZED EARLY ON THERE
WAS A NEED FOR DIVERSE EXPERTISE
IN VARIOUS DISCIPLINES TO
PROPERLY ASSESS AND OVERSEE THE
RESEARCH BEING FUNDED THROUGH
"BRAIN."
SOME OF OUR MEMBERS FROM THE
I.C. ADVISORY COUNCILS, SOME OF
THEM AT-LARGE MEMBERS WHO WERE
ADDED TO SUPPLEMENT THE WORKING
GROUP'S EXPERTISE.
WE ALSO HAVE SEVERAL EX OFFICIO
MEMBERS FROM DARPA, FDA, IARPA,
NSF, THESE ARE FOUR OF OUR
FEDERAL PARTNERS IN THE BRAIN
INITIATIVE.
WE DEPEND UPON THE MULTI-COUNCIL
WORKING GROUP FOR ONGOING
OVERSIGHT OF SCIENTIFIC VISION
AND PROGRESS BEING MADE UNDER
THE BRAIN INITIATIVE, FOR
FEEDBACK ON CONCEPT CLEARANCES
THAT ARE PRESENTED FOR
CONSIDERATION AS NEW
INITIATIVES, AND FOR INPUT ON
OUR FUNDING PLANS AND WE DO THIS
DURING THE CLOSED SESSION.
THE OPEN SESSION, WHICH IS WHERE
WE ARE RIGHT NOW, IS BEING
VIDEOCAST AND RECORDED, AND IT
WILL BE ARCHIVED AND POSTED ON
THE NIH AND THE BRAIN WEBSITES.
TODAY WE'RE PLEASED TO WELCOME
SEVERAL NEW MEMBERS TO THE
MULTI-COUNCIL WORKING GROUP,
DOCTORS ANGIE LAIRD, FROM NIDA'S
COUNCIL, CONSIDER TOW WAGER FROM
NCCIH, AND DR. KATHY ZAKOWSKI
FROM NICHD, BIDDING FAREWELL TO
THREE OTHER MEMBERS, BRUCE HAS
BEEN WITH US SINCE BRAIN
STARTED.
JOHN WILL WELCOME NEW MEMBERS
AND ACKNOWLEDGE THE
CONTRIBUTIONS OF THOSE WHO ARE
ROTATING OFF IN JUST A FEW
MINUTES, DURING HIS GENERAL
UPDATE ON "BRAIN."
AFTER THAT, WE WILL GET A BRIEF
UPDATE ON THE ACTIVITIES OF THE
NEUROETHICS WORKING GROUP WHICH
MET YESTERDAY, AND HAD
INTERESTING DISCUSSIONS AROUND
ETHICAL ISSUES PERTAINING TO
A.I. AND PSYCHIATRY AND
NEUROSCIENCE.
AND THEN FOLLOWING THAT, DR.
TIRIM MOORE, AN MCWG MEMBER,
WILL GIVE A PRESENTATION ON
RESEARCH HE'S BEEN CONDUCTING IN
HIS LABORATORY.
FOLLOWING THE OPEN SESSION WE'LL
HAVE A 30-MINUTE BREAK BEFORE
BEGINNING THE CLOSED SESSION,
AND I WILL GO OVER SOME OF OUR
OPERATING PROCEDURES FOR CLOSED
SESSION AT THAT TIME.
WE EXPECT THAT TO START AROUND
2:30.
NOTE THAT THERE'S A DIFFERENT
ZOOM LINK FOR THE CLOSED
SESSION, AND THAT IS FOR MEMBERS
OF THE WORK GROUP AND GOVERNMENT
EMPLOYEES ONLY.
HOUSEKEEPING ITEMS, DURING THE
SLIDE PRESENTATION WE ASK YOU TO
MUTE YOUR LINE.
DURING DISCUSSION, WE'D LIKE YOU
TO TURN YOUR VIDEO ON AND USE
THE RAISE HAND OPTION, IF YOU
HAVE QUESTIONS, WE'LL CALL ON
YOU TO UNMUTE YOURSELF, PHYSICAL
HANDS ARE ALSO ACCEPTABLE.
BECAUSE THIS IS AN OPEN SESSION
AND BEING VIDEOCAST, WE PREFER
THAT YOU NOT USE THE CHAT
FUNCTION FOR DISCUSSION SINCE
THAT'S NOT VISIBLE THROUGH THE
VIDEOCAST.
AND FINALLY, I WANT TO THANK THE
OUTSTANDING TEAM WHOSE HARD WORK
GOES INTO PREPARING FOR THIS
MEETING, IN PARTICULAR DR.
DUPRE, DR. NINA HSU, DEB FRENER
AND MICHELLE PETERSON, SO MUCH
BEHIND-THE-SCENES WORK, AND ALL
OF YOU KNOW THEY ARE SPECTACULAR
AND THEY ARE ALSO A PLEASURE TO
WORK WITH.
AT THIS POINT, IF ANYONE IS
HAVING TECHNICAL PROBLEMS E-MAIL
KRISTIN AND SHE AND HER TEAM
WILL HELP SORT THINGS OUT FOR
YOU.
AND AT THIS TIME, I WILL TURN IT
OVER TO JOHN FOR HIS UPDATE ON
"BRAIN."
>> THANKS, SUSAN.
WELCOME, EVERYBODY, TO THE
AUGUST MEETING OF THE BRAIN
MULTI-COUNCIL WORKING GROUP.
GREAT TO SEE EVERYBODY.
THANK YOU TO THE MEMBERS FOR
BEING HERE, SPECIAL THANKS TO
SUSAN, ALSO TO KRISTIN, MICHELLE
AND NINA, FOR ALL THEY DO TO PUT
THIS TOGETHER.
WE HAVE A GREAT DAY COMING UP
AND IT'S REALLY ALL DUE TO THEIR
TIRELESS EFFORTS ON EVERYONE'S
BEHALF.
SO, LET ME SEE.
LET ME GIVE UPDATES HERE.
WE HAD SOME EARLIER TECHNICAL
ISSUES, BUT HOPEFULLY WE CAN GET
AROUND THAT.
UH-OH.
OKAY.
HERE WE GO.
CAN YOU SEE MY SCREEN?
>> ALL GOOD.
>> WE'RE GOOD?
OKAY, THANKS.
OKAY, YEAH, SO SOME QUICK MEMBER
UPDATES, AS SUSAN SAID, WE'RE
BIDDING FAREWELL TO HUGO BELLEN.
I DON'T THINK HE'S HERE, THE
REPRESENTATIVE FOR THE CHILD
HEALTH.
KAF DZIRASA, THANKS FOR ALL
YOU'VE DONE TO HELP ME LEARN A
LOT AND SEE THINGS IN SO MANY
DIFFERENT WAYS.
BRUCE, IF I COULD SING, I WOULD
SING BREAKING UP IS HARD TO DO.
YOU'VE BEEN HERE SINCE THE
OUTSET.
ON BEHALF OF BRAIN, I'VE
APPRECIATED YOUR WISDOM, HUMAN,
GENEROSITY.
I KNOW WHERE TO FIND YOU.
WE HAVE NEW FOLKS COMING ON.
NEW REPRESENTATIVE FOR THE NIDA
ANGIE LAIRD FROM FLORIDA
INTERNATIONAL UNIVERSITY, REALLY
THROILD
THRILLED TO HAVE YOU.
TOR WAGER FROM DARTMOUTH,
INTEREST IN NEUROPHYSIOLOGY AND
EFFECTIVE PROCESS, NEW
REPRESENTATIVE FOR NCCIH,
LOOKING FORWARD TO WORKING WITH
YOU.
DELIGHTED TO SEE YOU AT
YESTERDAY'S NEWG MEETING.
AND KATHY ZACKOWSKI, NATIONAL
M.S. SOCIETY SO WELCOME.
REALLIY LOOKING FORWARD TO
WORKING WITH YOU AS YOU BRING
YOUR NEW AND FRESH PERSPECTIVES
TO ALL WE DO IN "BRAIN" AS WE'RE
LOOKING FORWARD.
I HAVE THE PRIVILEGE TO WORK
WITH A TERRIFIC GROUP OF FOLKS
IN THE IMMEDIATE OFFICE, THEY
ARE ALL HERE, SHOWN HERE.
ONE OF THE THINGS WE DO AROUND
NIH IS WE HOST AND WORK WITH
FELLOWS, PhDs LOOKING TO
TRANSITION FROM PERHAPS BENCH
SCIENCE INTO POLICY,
COMMUNICATION, OUTREACH, WHAT
HAVE YOU.
THIS PAST YEAR WE WERE DELIGHTED
TO HAVE LIZ AKINBYIYI JOIN US,
Ph.D. FROM CASE WESTERN,
WORKING WITH US, LEARNING HOW
NIH WORKS, AND NOW WILL BE
JOINING NIH'S OFFICE OF
LEGISLATIVE POLICY AND ANALYSIS,
AND FOR THE MANY BRAIN BLOGS
THAT YOU HOPEFULLY READ ABOUT,
LIZ WAS THE BRAINS BEHIND THE
BRAIN BLOGS.
LIZ, GOOD LUCK.
WE ENJOYED HAVING YOU, TAKE
GREAT LESSONS WITH YOU TO YOUR
NEXT CHAPTER OF YOUR NIH
FELLOWSHIP.
ALL THAT WE DO IS ORGANIZED
ACROSS THESE SCIENTIFIC TEAMS
LISTED HERE.
GREAT GROUP OF FOLKS, AS WE TRY
TO INTEGRATE ACROSS THE
PORTFOLIO, ORGANIZING ACTIVITIES
OF I THINK PROBABLY OVER 150
FOLKS WORKING ACROSS THESE
TEAMS, ACROSS NIH, INEVITABLY AS
SOON AS THIS MEETING IS OVER I'M
GETTING AN E-MAIL FROM SOMEBODY,
YOU MISSED ME.
SO IF WE DID, LET US KNOW.
THIS IS OUR MOST UP-TO-DATE LIST
OF THE FOLKS WHO MAKE HUGE
CONTRIBUTIONS TO WHAT WE CALL
THE BRAIN INITIATIVE.
I WANT TO MAKE A FEW -- GO OVER
UPDATES IN THE COMMUNITY.
WE'RE THRILLED WITH THIS YEAR'S
KAVLI AWARDS IN NEUROSCIENCE FOR
DISCOVERY OF BASICALLY FACE
REPRESENTATIONS AND HUMAN AND
NON-HUMAN PRIMATE NEOCORTEX,
FIELD OFF BY NANCY KANWISHER,
MADE WHOLE TOGETHER WITH WINRICH
FREIWALD AND DORIS TSAO,
CELEBRATED IN OSLO IN A FEW
WEEKS FOR THIS RECOGNITION.
DR. PAUL ALIBANSANTOS, ONE OF
THE ORIGINAL PLAYERS GETTING
THIS BRAIN ACTIVITY MAP, THE
PRECURSOR TO THE BRAIN
INITIATIVE, BACK IN 2012 OR SO,
WAS ALSO AWARDED THE KAVLI AWARD
FOR PIONEERING WORK IN THE
CREATION OF NANODOTS, SO VERY
EXCITING TIME IN SCIENCE, A
GREAT CONVERGENCE OF
NEUROSCIENCE COMPUTATION AND
EVERYTHING ELSE WE DO.
WE'RE THRILLED THAT THESE
SCIENTISTS WERE RECOGNIZED FOR
THEIR GROUNDBREAKING WORK.
OKAY.
SO WE'VE BEEN BUSY FOR THE PAST
BIT SINCE WE LAST MET.
WE'RE CELEBRATING A DECADE OF
INNOVATION, TEN YEARS OF BRAIN.
THE BRAIN INITIATIVE WAS
ANNOUNCED IN 2013 WITH FIRST
AWARDS MADE IN 2014, AND TO
CELEBRATE WHAT WE'VE BEEN DOING
AND THE CONTRIBUTIONS WE'VE BEEN
MAKING ACROSS THE FIELD, WE'VE
ROLLED OUT I THINK A NICE THING
WHICH IS TO HAVE EACH OF OUR TEN
BRAIN I.C.s WRITE A
PERSPECTIVE ABOUT HOW BRAIN HAS
IMPACTED THEIR MISSION AND VICE
VERSA, JOSH GORDON HAS MOVED ON
NOW, A CIVILIAN, CHAIR OF
PSYCHIATRY AT COLUMBIA WROTE A
NICE PIECE, DIANA BIANCHI,
SO-AND-SO FORTH, WE'LL HAVE MORE
COMING OUT OVER THE NEXT MONTH
OR TWO TO ROUND OUT ALL TEN.
STAY TUNED, IF YOU'RE CUB
--
SUBSCRIBED CAN YOU SEE THESE,
ONE FROM DEB TUCCI A FEW DAYS
AGO.
WE JUST HAD THE TENTH ANNUAL
BRAIN INITIATIVE CONFERENCE IN
JUNE FEATURING GREAT STUFF, SOME
TERRIFIC PLENARY LECTURES,
SYMPOSIA, SPECIALTY SESSION,
POSTER SESSIONS WHICH ARE REALLY
EXCITING, SCHOLAR SPOTLIGHTS AND
EARLY CAREER SCHOLAR EVENT THE
NIGHT BEFORE.
LET ME SHOW YOU IN PICTURES WHAT
WE DID.
THIS WAS THE PRE-EVENT, EARLY
CAREER RESEARCHER EVENT
WELCOMING FOLKS FROM THE STUDENT
PHASE THROUGH EARLY ASSOCIATE
PROFESSORS.
THIS WAS ORGANIZED BY OFFICE OF
BRAIN DIRECTOR AND WAS A
TERRIFIC NETWORKING EVENT.
WE HAVE A VIRTUAL COMPONENT,
PEOPLE WERE ALSO ABLE TO
PARTAKE, VERY EXCITING, LOOKING
FORWARD TO CONTINUING INTO THE
FUTURE.
THE FIRST DAY WE HAD A GREAT
TIME.
WE HAD OPENING AS WELL AS
SCHOLAR SPOTLIGHTS, HERE IN THE
MIDDLE SHOWS THE FOLKS THAT WON
THE SCHOLAR SPOTLIGHTS AWARD.
THEY GAVE FLASH TALKS THAT GAVE
PREVIEWS FOR FOLKS TO COME SEE
THEIR POSTERS LATER IN THE DAY.
DR. LEE CHEN LO FROM STANFORD
GAVE AN AMAZING TALK ON HIS
LAB'S WORK ON SERATONERGIC
SYSTEM IN MICE.
HE DESCRIBED AT LEAST THREE BIG
PAPERS' WORTH OF DATA AND
RESULTS AND FINDINGS NOT YET
PUBLISHED, REALLY A GREAT SPIRIT
OF BEING OPEN AND SHARING ABOUT
OUR SCIENCE.
FINALLY IN THE AFTERNOON WE HAD
A PANEL WITH FRANCIS COLLINS,
CORY BERGMAN, EDDIE CHANG,
CAROLINE, TO THINK ABOUT HOW FAR
BRAIN CAME IN TEN YEARS WITH A
LOOK TO THE FUTURE.
THAT WAS I THINK A GREAT DAY,
THE FIRST DAY.
THE SECOND DAY CONTINUED, POSTER
SESSIONS, WE HAD AN AMAZING TALK
BY VIVIANA, VECTORS FOR
ACCESSING THE BRAIN, PART OF OUR
EFFORT TO DEVELOP TOOLS FOR
PRE-VISION BRAIN, THERE'S WALTER
ASKING A QUESTION.
VARIOUS SYMPOSIA SPECIALTY
SESSION, A GROUP REACHES
SECONDARY SCHOOLS IN THE
COMMUNITY TO GET KIDS INTERESTED
IN NEUROSCIENCE, AND I'LL COME
BACK TO THAT, AS WELL AS LOTS OF
INTERACTIONS AND SUCH.
PART OF WHAT WE DO AT THE BRAIN
INITIATIVE CONFERENCE IS WE
ANNOUNCE THE WINNERS OF OUR
PHOTO AND VIDEO CONTEST.
I WANT TO SHOW YOU A LITTLE BIT
OF EYE CANDY HERE.
THIS IS FROM PURDUE UNIVERSITY,
USING WHAT THEY INVENTED, ARRAY
TO IMAGE CORTEX AT SCALE IN VIVO
WITH TWO-PHOTON IMAGING, VERY
COOL.
AND A NICE VIDEO FROM HAO-CHENG
GAO AT PURDUE, 3D
NANOARCHITECTURE OF MEMBRANES OF
THE DENDRITIC SPINE BY LABELING
CHANNELRHODOPSIN.
OKAY.
AND MANY OTHERS, AND I THINK
YOU'LL BE SEEING THE VARIOUS
AWARDEES AS WE ISSUE OUR BRAIN
CALENDAR.
IF YOU COME BY THE BOOTH I
BELIEVE IN OCTOBER, IN CHICAGO,
WE MIGHT HAVE A FEW TO PASS OUT
THERE.
OKAY.
NONE OF THIS COULD HAVE HAPPENED
WITHOUT THE VILLAGE THAT IT TOOK
TO PUT THIS THING TOGETHER, A
TERRIFIC PROGRAM COMMITTEE,
FOLKS FROM THE FEDERAL AND
NON-FEDERAL ORGANIZATIONS AS
WELL AS FOLKS IN THE EXTRAMURAL
COMMUNITY, AND WE HAD SOME
WONDERFUL SPONSORS.
I WANT TO CALL OUT IN PARTICULAR
GINA SAMPSON AND OUR OFFICE WHO
TOOK THE LEAD ON PUTTING THIS
WHOLE THING TOGETHER.
A HERCULEAN EFFORT AS YOU CAN
IMAGINE, AS WELL AS CRYSTAL AND
IVANA, WHO SPEARHEADED THE EARLY
CAREER BIT.
IT WAS A GREAT TEAM EFFORT.
AND JUST TO LET YOU KNOW FOR A
VARIETY OF REASONS WE DECIDED TO
MOVE THIS BRAIN CONFERENCE WHICH
IS A HUGE LIFT TO A BIANNUAL
CADENCE, WE'LL SEE YOU AGAIN IN
2026, DETAILS FORTHCOMING.
IN THE OFF YEARS WE'LL BE
PUTTING ON VARIOUS WORKSHOPS,
SMALLER FOR FOCUSED OTHER
ACTIVITIES, WE'RE GOING TO USE
THE TIME DIFFERENTLY AND ENGAGE
A GREATER PART OF THE FEEL.
WE'VE HAVE ACCESS TO VIRTUAL
PROGRAM, SO THE MEETING, THE
MAIN SESSIONS WERE ALL RECORDED,
YOU CAN ACCESS THAT IF YOU GO TO
OUR WEBSITE AND FIND IT OR USE
THIS QR CODE, ACCESS THE VIRTUAL
PLATFORM, A LOT OF GREAT TALKS
AND STUFF TO REVIEW, THE PIPE
CLEANER NEURON I'M HOLDING IN
TRUST ON BEHALF OF ALL OF US.
HOPE TO SEE YOU AGAIN IN 2026 AT
THE MAY MEETING BUT LOTS OF
OPPORTUNITIES TO CONVENE BEFORE
THEN.
OKAY.
SO THAT WAS THE BRAIN MEETING.
OTHER ACTIVITIES WE HAD BACK IN
MAY, WE HAD A BRAIN INITIATIVE
WORKSHOP ON ADVANCING HUMAN
NEUROSCIENCE THROUGH
NEUROSTIMULATION AND RECORDING,
A VERY HOT TOPIC.
WE WANTED TO EXPLORE THE
CHALLENGES AND OPPORTUNITIES
ASSOCIATED WITH THESE EFFORTS TO
UNDERSTAND RELATIONSHIP BETWEEN
BRAIN FUNCTION AND HUMANS, AND
BEHAVIOR THROUGH
NEUROSTIMULATION RECORDING.
AND YOU CAN FIND OUT MORE ABOUT
THAT BY CLICKING ON THAT LINK OR
LOOKING UP VIA THE QR CODE.
AT THE ANNUAL MEETING FOR THE
SOCIETY OF NEUROSCIENCE IS A
SATELLITE EVENT COMING UP,
ORGANIZED AND SPONSORED BY THE
BRAIN INITIATIVE ALLIANCE, SO
THIS IS THE TOOL MAKER
SYMPOSIUM.
THIS IS JUST A QUICK SNAP FROM
LAST YEAR'S EVENT.
YOU CAN SEE A LOT OF GREAT
ACTIVITY.
WE GET FOLKS SUPPORTIVE BY US TO
SHOW THEIR TOOLS AND TO GET
PEOPLE EXCITED ABOUT WHAT THEY
ARE DOING AND HOPEFULLY TO
STIMULATE NEW AND INTERESTING
COLLABORATIONS.
THIS WILL BE HELD ON SUNDAY,
OCTOBER 6, 6:30 P.M., MORE
INFORMATION WILL BE COMING.
YOU CAN FIND MORE INFORMATION
BOTH ON OUR WEBSITE AS WELL AS
THE BRAIN INITIATIVE BIA
WEBSITE.
OKAY.
SO, LET'S SEE.
LET'S JUST TALK ABOUT BUDGET.
JUST A FEW UPDATES, NOTHING HAS
HAPPENED SINCE WE LAST SPOKE.
AS YOU RECALL, THIS YEAR AND FY
24 THAT ENDS SEPTEMBER 30 OF
THIS YEAR, WE EXPERIENCED
DECREASE OF $278 MILLION
RELATIVE TO OUR FY 23 BUDGET.
I WENT THROUGH THIS BEFORE.
REAL QUICK, BRAIN GETS ITS
FUNDING FROM TWO SOURCES, ONE IS
THE BASE APPROPRIATIONINGS TO
TEN BRAIN I.C.s, THAT
PARTICIPATE IN BRAIN.
THAT'S SHOWN IN BLUE.
AND THEN FROM ADDITIONAL FUNDS
AUTHORIZED BY THE 21ST CENTURY
CURES ACT IN PINK ALONG THE TOP,
THIS MONEY FLUCTUATES YEAR TO
YEAR ENDS AFTER 2026.
IN FY 23 TO MAKE ROOM FOR THIS
LARGE BUMP UP IN CURES FUNDS, A
FUNNY THING THAT GOES ON, THIS
INCREASE TO $450 MILLION, THE
BASE APPROPRIATION WAS CUT BY
$238 MILLION, SO THE TOTAL
AMOUNT THAT WE GOT IN 23, FY 23,
WAS 680 WHICH REPRESENTED A $60
MILLION INCREASE FROM FY 22, SO
WE WERE UP THROUGH 2023 STILL
RIDING THIS NICE INCREASING WAVE
OF FUNDING WITH WHICH WE'VE BEEN
ABLE TO SUPPORT AMAZING SCIENCE.
SO, THE LITTLE SNAFU CAME IN
2024 WHEN THE CURES ACT FUNDS
WAS PRESCRIBED TO DECREASE BY
$278 MILLION, THAT MONEY DIDN'T
GO BACK INTO THE BASE SO WE WERE
STUCK WITH THAT DECREASE THERE.
SO THAT'S WHERE WE ARE RIGHT
NOW.
AND RIGHT NOW WE'RE ALL EAGERLY
AWAITING THE FINAL BUDGET FOR FY
25, WHICH IS I THINK, ANYBODY
READING PAPERS, WILL REALIZE
IT'S UP IN THE AIR.
OKAY.
THIS IS WHERE WE ARE TODAY.
SO WHAT DOES IT LOOK LOOK FOR FY
25 BUDGET PRESUMABLY STARTING
OCTOBER 1?
THE PROCESS GOES, HOUSE COMES UP
WITH PROPOSALS, SENATE COMES UP
WITH A BUDGET PROPOSALS, THEY
MEET TO WORK OUT COMPROMISE
DEAL, EVENTUALLY THE PRESIDENT
SIGNS INTO LAW.
THE WAY THINGS STAND NOW HOUSE
BUDGET KEEPS OUR APPROPRIATION,
BASE APPROPRIATION, THE BLUE
PART FLAT AT $230 MILLION.
OKAY.
NOW, THE CURES AUTHORIZATION
DROPS IN 2025 BY $81 MILLION
FROM 172 TO 91 MILLION, WHICH
WOULD GIVE $321 MILLION TOP LINE
BUDGET COMPARED TO FY 24 BUDGET
OF $402, SO $81 MILLION
DECREASE, THAT'S WHAT THE HOUSE
BUDGET LOOKS LIKE.
NOW, AN AMENDMENT WAS INTRODUCED
BY REPRESENTATIVE LUTTRELL,
CO-CHAIR OF THE CONGRESSIONAL
NEUROSCIENCE CAUCUS, HIS
AMENDMENT PROPOSES TO INCREASE
THE BRAIN BUDGET BY $81 MILLION
TO BRING US BACK UP FLAT TO
CURRENT YEAR FUNDING OF FY 24.
SO, THAT'S WHAT HAPPENED.
THERE ARE MANY AMENDMENTS PUT
INTO THE BILL, HOUSE RECESSED
BEFORE FLOOR VOTE.
IT WAS NEVER VOTED ON.
WHAT WILL HAPPEN WE DON'T KNOW.
THE SENATE MET, THEIR BUDGET
PROPOSALS HAS FULL RESTORATION
OF BRAIN TO FY 23 LEVELS, SO
PROPOSING TO ADD -- TO INCREASE
BUDGET RELATIVE TO THIS YEAR BY
$359 MILLION, BRINGING US UP TO
$680 MILLION, WHERE WE WERE AT
FY 23.
STRONG BIPARTISAN SUPPORT FOR
NIH IN GENERAL, AND BRAIN, AND
OTHER CURES ACT PROGRAMS IN
PARTICULAR.
VERY HEARTENING.
WE HAVE CLEAR SUPPORT FROM BOTH
SIDES OF THE AISLE FROM THE
CHAIR BALDWIN AS WELL AS RANKING
MEMBER CAPITO, AND PASSED ON
25-3 VOTE.
HOWEVER, WITH ELECTION COMING UP
WE EXPECT CONTINUING RESOLUTION
UNTIL AT LEAST AFTER THE
NOVEMBER ELECTIONS, AND WE'LL
SEE HOW SOON WE CAN GET A BUDGET
PUT IN PLACE.
THIS YEAR WE DIDN'T GET A BUDGET
UNTIL MARCH, HOPEFULLY WE'LL GET
ONE IN PLACE SOONER.
THAT'S WHERE THINGS STAND.
EVERYTHING STILL UP IN THE AIR.
BOTTOM LINE WE HAVE TO STAY THE
COURSE.
JUST KEEP FOCUSED ON OUR
PRIORITIES AND VALUES, WE'LL NOT
JUST WEATHER THE STORM BUT WE'LL
NAVIGATE THE STORM AND COME
THROUGH STRONG AS WE CAN.
SO AGAIN WE HAVE SOME PAGES ON
THE WEBSITE THAT GIVES
INFORMATION FOR EVERYBODY, AS
THEY WOULD LIKE TO FIND IT, ON
WHERE WE ARE ON THE BUDGET,
UPDATING FROM TIME TO TIME AS
THINGS CHANGE BUT RIGHT NOW THIS
IS WHERE THINGS STAND AT THE
MOMENT.
OKAY.
SO THAT'S WHERE WE ARE WITH THE
BUDGET.
PART OF ALL THIS INVOLVES OF
COURSE MAKING SURE THAT FOLKS
UNDERSTAND THE VALUE OF WHAT
WE'RE DOING SO WE'VE BEEN QUITE
ACTIVE IN ENGAGING THE COMMUNITY
ABOUT WHAT BRAIN IS DOING, NOT
JUST THE SCIENTIFIC COMMUNITY
BUT BROADER COMMUNITY.
AND WE KIND OF LOOK AT THIS IN
THREE OVERLAPPING BUCKETS,
INFORMING KEY STAKEHOLDERS,
CELEBRATING OUR COMMUNITY
IMPACT, EMPOWERING OUR COMMUNITY
VOICES.
SO WE'VE DONE A FEW THINGS SINCE
WE LAST MET.
I WANT TO GO THROUGH THIS
BRIEFLY.
WE HAD A WIDELY HELD BRIEFING IN
FRONT OF CONGRESSIONAL
NEUROSCIENCE CAUCUS IN APRIL.
ON THE LEFT IS REPRESENTATIVE
LUTTRELL, I MENTIONED HIM
BEFORE, CO-CHAIR OF THE
NEUROSCIENCE CAUCUS, EVENT
ORGANIZED BY OUR PARTNERS,
PRIMARILY OF THE AMERICAN BRAIN
COALITION, I BELIEVE DANA
FOUNDATION AND SIMONS, AS WELL.
WE HAD A BRIEFING WITH DR. TED
ABEL, WHO MODERATED, AND WE
BROUGHT IN A FEW FOLKS, DR.
HELEN mAbRIC, GROUNDBREAKING
STUDIES RECORDING BIOMARKERS
FROM PATIENTS SUFFERING FROM
TREATMENT RESISTING DEPRESSION
USING THIS INFORMATION TO HELP
THEM TO A BETTER STATE.
TOGETHER HERE IS MR. JOHN NELSON
AND HIS WIFE, MRS. BARBARA
NELSON.
MR. NELSON WAS ONE OF HER
PATIENTS AND TOLD THE STORY HOW
THIS THERAPY GAVE HIM HIS LIFE
BACK.
ALSO ON THE PANEL WAS DR.
SUDANO, SOME OF OF YOU KNOW HAS
DONE PIONEERING WORK IN
DEVELOPING BRAIN RECORDING AND
MODULATION TECHNOLOGIES, AND I
THINK WE HAD A GREAT SESSION
THERE SHOWING FOLKS ON THE HILL
THE GREAT VALUE OF BRAIN, HOW
WE'RE HELPING PEOPLE TODAY AND
HOW WE'RE GOING TO LAY DOWN THE
FOUNDATION FOR FUTURE CURES
USING THIS AMAZING APPLICATION
OF THESE SIMULATION
TECHNOLOGIES.
YOU'LL SEE SOME -- THE BACK
SYSTEM, FRONT ROW OF THE
BRIEFING, IT HAPPENED THAT THE
DATE COINCIDED WITH THE MEETING
OF THE SFM COUNCIL, LITERALLY
BUSED HERE TO SEE THE IMPORTANCE
OF WHAT WE'RE DOING, ALSO IN THE
CONTEXT OF GETTING THIS WORD OUT
TO THE FOLKS ON THE HILL WHO ARE
OF COURSE THE ONES THAT ALLOW US
TO DO THIS WORK THROUGH THEIR
APPROPRIATIONS.
SO THAT WAS BACK IN APRIL.
COMING UP, MY TEAM IS GOING TO
BE VISITING THE HOUSTON AREA TO
VISIT BAYLOR COLLEGE OF
MEDICINE, ALSO TO PARTICIPATE IN
THIS SUMMIT THAT'S CALLED THE
AMERICAN BRAIN ECONOMY, LOOKING
AT THE APPROACHES AND STRATEGIES
WE NEED TO TAKE TO NOT ONLY
PRESERVE BUT PROMOTE OUR
NATION'S GREATEST RESOURCES,
WHICH IS OUR BRAINS.
AND ALSO PARTICIPATING IN THIS
WORKSHOP WILL BE REPRESENTATIVE
MORGAN LUTTRELL, WHO I
MENTIONED, AS WELL AS OTHER
MEMBERS OF CONGRESS AND FOLKS
FROM DIFFERENT AGENCIES AND
UNIVERSITIES.
WE'RE LOOKING FORWARD TO THAT TO
SHOWCASE WHAT WE CAN DO BY
PUSHING THIS TECHNOLOGY IN
NEUROSCIENCE.
WE HAD A CHANCE TO CELEBRATE NOT
JUST THE SUCCESS OF BRAIN BUT
OUR CHAMPIONS.
SHOWN HERE AN EVENT I ATTENDED
IN MAY AT OREGON HEALTH AND
SCIENCE UNIVERSITY IN PORTLAND,
AND THEY PUT ON AN EVENT TO
CELEBRATE THE CONTRIBUTIONS OF
REPRESENTATIVE EARL BLOOMENAUER,
THE CO-CHAIR, MORGAN LUTTRELL,
COUNTERPART, HE FOUNDED THE
CONGRESSIONAL NEUROSCIENCE
CAUCUS, OH, I THINK JUST BEFORE
BRAIN STARTED.
HE WAS INSTRUMENTAL IN PROMOTING
"BRAIN" ON THE HILL.
HE'S BEEN A FIERCE ADVOCATE FOR
NEUROSCIENCE AND NEUROSCIENCE
RESEARCH, AND THIS IS A GREAT
OPPORTUNITY TO CELEBRATE HIS
CONTRIBUTIONS AND IT WAS JUST A
DELIGHT TO BE THERE TO REPRESENT
"BRAIN."
ON THE LEFT IS DR. MARK RESNICK,
CHAIRMAN OF THE BOARD OF THE
AMERICAN BRAIN COALITION.
SO THAT WAS A GREAT TIME UP
THERE.
AND THEN WE ALSO HAD THE
OPPORTUNITY TO VISIT THE
PRINCETON NEUROSCIENCE INSTITUTE
A LITTLE BIT LATER IN MAY, AND
HAD THE PLEASURE OF BEING JOINED
BY REPRESENTATIVE BONNIE WATSON
COLEMAN, IN WHOSE DISTRICT
PRINCETON RESIDES.
I GOT TO SEE A LOT OF GREAT
SCIENCE BEING DONE THERE BUT
ALSO WE HAD A VERY NICE TOUR OF
THE AMAZING FACILITIES THEY HAVE
DEVELOPED IN MICROSCOPY,
IMAGING, SO FORTH.
WE GOT TO SEE -- YOU SEE THE
BRAIN CONNECTS POSTER THERE,
VERY NICELY FORTUITOUSLY THE
SAME COLOR SCHEME OF THE
REPRESENTATIVE'S SUIT, BUT WE
ALSO GOT TO SEE THE NEWLY
INSTALLED AND AT THAT TIMED
RUNNING MULTI-BEAM SCANNING
ELECTRON MICROSCOPE THAT WAS
ACQUIRED AND INSTALLED AS PART
OF THE BRAIN CONNECTS PROGRAM,
SO VERY EXCITING CUTTING EDGE
WORK.
ON THE RIGHT YOU SHOO SEE ME WE
DIRECTOR OF PNI, AN BRAD
DICKERSON, RECENT HIRE, A BRAIN
AWARDEE, WHEN REPRESENTATIVE WAS
IN LOCAL POLITICS HE WORKED IN
ONE OF HER LOCAL OFFICES,
CONNECTIONS ARE AMAZING AND
WE'RE DELIGHTED WE HAD A CHANCE
TO SEE THE GREAT WORK THEY ARE
DOING.
THEY HAD A CHANCE TO SHOWCASE
THE IMPORTANT WORK THEY ARE
DOING WITH BRAIN SUPPORT TO
THEIR MEMBER OF CONGRESS.
OKAY.
SO, WE JUST WANT TO MAKE SURE
THAT EVERYBODY HAS THE TOOLS
THEY NEED TO KIND OF PROMOTE THE
GREAT THINGS WE'RE DOING.
THIS IS ON OUR WEBSITE.
WE HAVE THIS COMMUNICATIONS
TOOLKIT.
IF YOU HAVE QUESTIONS OR NEEDS,
LET US KNOW.
WE'RE HAPPY TO HELP YOU GET THE
WORD OUT ABOUT WHAT WE'RE DOING
IN THE BRAIN INITIATIVE.
OKAY.
SO, LET'S SEE.
WE'RE DOING OKAY ON TIME, YEAH?
I'LL GIVE A FEW UPDATES WITH THE
PROGRAM.
BRAIN HAS SIGNED ON TO THIS NIH
BLUEPRINT, OUR SISTER PROGRAM,
ENDURE PROGRAM, WHICH SEEKS --
R25 PROGRAM THAT SEEKS TO BRING
IN FOLKS AT UNDERGRADUATE
UNIVERSITIES AT THE VERY
BEGINNING OF THE PIPELINE, AND
THERE WILL BE A WEBINAR HELPING
PEOPLE UNDERSTAND THE PROGRAM SO
THEY CAN BE WELL POSITIONED TO
APPLY.
THIS WILL BE ON AUGUST 27, 2 TO
3:00 P.M., YOU CAN REGISTER AT
THAT LINK.
I ALSO WANT TO -- LET'S SEE.
THIS IS -- WE TALKED ABOUT THIS
AS A CONCEPT NOT LONG AGO.
THIS IS A NOTICE OF INTENT TO
PUBLISH.
NEW FUNDING OPPORTUNITY.
NOT YET ON THE STREET.
BUT IT WILL BE PUBLISHED, WE
HOPE, A LITTLE BIT LATER THIS
YEAR.
AND THIS IS TO SOLICIT
APPLICATIONS FOR TARGETED
DISSEMINATION OF VALIDATED BRAIN
TOOLS TO INVESTIGATORS AT
INSTITUTIONS THAT DON'T RECEIVE
A LOT OF RESEARCH SUPPORT.
SO THIS IS KIND OF A LITTLE BIT
OF A DIFFERENT APPROACH WE'RE
TAKING, TRYING TO GET OUR TOOLS
INTO MORE PEOPLE'S HANDS AT
DIFFERENT INSTITUTIONS TO KIND
OF BRING IN MORE TALENT ACROSS
THE COUNTRY WHERE FOLKS DON'T
NECESSARILY HAVE ACCESS.
SO YOU'LL LEARN MORE ABOUT THAT,
YOU CAN CLICK ON THAT QR CODE TO
LEARN MORE AND EXPECT TO SEE
NOTICE OF FUNDING OPPORTUNITY
THIS FALL, OUR OWN DR. NATALIE
TRZCINSKI IS OVERSEEING THAT.
CONTACT HER IF YOU HAVE
QUESTIONS.
LET'S SEE.
FOR ADDITIONAL FUN STUFF LET ME
HIGHLIGHT FOR YOU -- I THINK I
HAVE THROUGH OR FOUR RECENT
PUBLICATIONS THAT WILL BE OF
INTEREST ACROSS THE DOMAIN FROM
TOOLS TO CIRCUITS, TO HUMAN
NEUROSCIENCE.
SO AS I THINK SOME OF YOU CAN
APPRECIATE ONE OF THE BIG
PROJECTS THAT WE'RE QUITE
INTERESTED IN IS THIS SO-CALLED
ARMAMENTARIUM FOR PRECISION
BRAIN CELL ACCESS TO DEVELOP
TOOLS THAT ALLOW RESEARCHERS
USING THE EMERGING INFORMATION
ABOUT CELL TYPES, MOLECULAR
PROPERTIES, CIRCUIT PROPERTIES,
CONNECTIVITY PROPERTIES, TO
START ASKING SPECIFIC QUESTIONS
ABOUT HOW THOSE CELLS AND
CIRCUITS ARE INTERACTING TO GIVE
RISE TO BEHAVIOR.
NOW, THE LONG RANGE BLUE SKY
GOAL USING THIS INFORMATION,
THIS INFORMATION IN SOME, ONE
DAY SOON, WILL ALLOW US TO START
THINKING ABOUT PRECISION CIRCUIT
THERAPIES INCLUDING PRECISION
GENE THERAPIES IN THE NERVOUS
SYSTEM.
IF WE'RE THINKING ABOUT GENE
THERAPIES IN HUMANS, A BIG
CHALLENGE IS GETTING THESE
PAYLOADS, WHETHER A GENE EDITOR
OR FIXED GENE, INTO THE CELLS OF
INTEREST WHICH WOULD BE IN THE
BRAIN IN OUR CASE.
AND KEEPING THEM AWAY FROM LIKE
THE LIVER AND KIDNEY WHERE THEY
ARE TOXICS WITH A DELIVERY
SYSTEM STRAIGHTFORWARD.
NOW, THERE HAVE BEEN
BREAKTHROUGHS IN TERMS OF
DEVELOPING THESE ADENOASSOCIATE
VIRUS CAPSIDS DELIVERED INTO THE
BLOODSTREAM BUT THE CATCH IS
GETTING THEM ACROSS THE
BLOOD-BRAIN BARRIER.
THIS WAS THE TOPIC OF THE
PLENARY TALK THEY BRAIN MEETING.
HERE IS A COOL PAPER JUST OUT
FROM BEN DEVERMAN AT THE BROAD.
THIS IS A PROJECT THAT WAS
SUPPORTED BOTH BY THE BRAIN
INITIATIVE AS WELL AS FROM THE
COMMON FUND, NIH COMMON FUND
SOMATIC CELL GENOME EDITING
PROGRAM.
GREAT COLLABORATION BETWEEN
THESE DIFFERENT PROGRAMS, NICE
DOVETAIL BETWEEN THESE EFFORTS.
AND SO WHAT THEY DID IS THEY
TOOK THE CAPSID OF ONE OF THESE
AAVs, INVERTED RANDOM SEVEN
PEPTIDE SEGMENTS IN IT AND
SELECTED THEM BASED ON ABITE TO
BIND TO HUMAN TRANSFERRIN
RECEPTOR, INVOLVED IN
TRANSPORTING MOLECULES ACROSS
THE BLOOD-BRAIN BARRIER IN
HUMANS, EXPRESSED IN THE
VASCULATURE.
AND THEY FOUND A VARIANT THAT
DOES CROSS THE -- DOES BIND TO
THE HUMAN TRANSFERRIN RECEPTOR
AND MADE A HUMANIZED MOUSE, TOOK
A MOUSE AND THEY REPLACED THE
MOUSE TRANSFERRIN RECEPTOR WITH
HUMAN VARIANT, CAN SHOW IT
ACTUALLY TRANSDUCES LOTS OF
CELLS INTO THIS HUMANIZED MOUSE,
ONE OF THE PAYLOADS THAT HE USED
THIS GENE IDENTIFIED AS BEING
GAUCHER'S DISEASE, SHOWED PROOF
OF PRINCIPLE THEY CAN NOW HAVE
AAV VECTOR WHICH IN THEORY
SHOULD BE ABLE TO CROSS THE
HUMAN BLOOD-BRAIN BARRIER IF THE
HUMANIZED MOUSE IS A GOOD PROXY
GETTING A PAYLOAD IN FOR A
DISEASE-RELEVANT GENE, ONE STEP
IN A LONG JOURNEY TOWARD
DEVELOPING HUMAN GENE THERAPIES
USING AAV VECTORS IN THIS
DIRECTED APPROACH.
STAY TUNED.
VERY EXCITING WORK.
THIS IS JUST ONE OF I THINK MANY
EXCITING DEVELOPMENTS COMING OUT
OF OUR ARMAMENTARIUM PROGRAM,
AND, YOU KNOW, I'M SURE THE BEST
WILL BE YET TO COME.
THERE'S A LOT OF WORK YET HERE
TO DO BUT WE'RE QUITE EXCITED BY
THIS DEVELOPMENT.
OKAY.
HERE IS A STUDY FROM LISA'S LAB
AT STANFORD.
HOW WE NAVIGATE OUR ENVIRONMENT
IS OF COURSE AN INTERESTING AND
CRITICAL QUESTION IN
NEUROSCIENCE, AND TO ENABLE
NAVIGATION, THE BRAIN HAS TO BE
ABLE TO REPRESENTATIVE AND
INTEGRATE DIFFERENT GEOMETRIC
FEATURES OF OUR ENVIRONMENT, SO
FOR EXAMPLE IF I'M NAVIGATING IN
A ROOM I NEED TO KNOW NOT TO
WALK INTO THE CORNER OF THE
ROOM, IF I'M ON THE STREET AND
THERE'S A BLOCKED DRIVEWAY I
HAVE TO KNOW NOT TO WALK INTO
THAT.
I'VE DONE THAT BEFORE, SADLY.
AND SO WHAT THEY HAVE ASKED IS
THEY HAVE FOUND IN THE SUBICULUM
NEURONS THAT ENCODE THE
LOCATIONS AND NOT JUST LOCATIONS
AND BOUNDARIES OF THE OBJECTS
BUT THEIR SHAPES.
SO THIS IS REALLY, REALLY COOL.
AND THEY DID THIS WITH CALCIUM
IMAGING USING A 1-PHOTON MINI
SCOPE, DEVELOPED AT UCLA, WITH
ANOTHER BRAIN GRANT, DID THIS IN
FREELY BEHAVING MICE.
YOU CAN SEE THE ACTIVITY
PATTERNS OF SPECIFIC CELLS THEY
ARE RECORDING FROM AS THESE MICE
TRAVERSE THE DIFFERENT PARTS OF
THE ENVIRONMENT.
I THINK YOU CAN SEE HEIGHTENED
ACTIVITY IN THE CORNER, CORNER
CELLS, CORNER CELLS HERE.
AND THEY ALSO FIND OTHER CELLS
THAT RESPOND TO CONVEX SHAPES,
RIGHT?
SO NOT THE CORNER OF A ROOM BUT
PERHAPS PROTRUSION OR AS I SAID
MAYBE A BOLLARD STICKING OUT IN
THE MIDDLE OF THE SPACE.
SUGGESTS THE SUBICULUM ENCODING
GEOMETRIC FEATURES COULD BE A
PIECE FOR BUILDING A COGNITIVE
MAP OF THE ENVIRONMENT, REALLY
NICE AND JUST GIVES US AN IDEA
ABOUT HOW SPATIAL ENVIRONMENT
MIGHT BE RECONSTRUCTED BASED ON
THESE DIFFERENT FEATURES, REALLY
BEAUTIFULLY ELEGANT WORK FROM
THE GIACOMA GROUP.
OKAY.
SO, HERE'S A STUDY OUT OF OUR
RESEARCH OPPORTUNITIES AND
HUMANS PORTFOLIO.
THIS WAS LED BY ANGELYNE, SID,
EVELYNE AND ZEB WILLIAMS AT MGH.
WE CAN ALL APPRECIATE HUMANS CAN
EXACT NUANCED MEANING FROM
LANGUAGE, BUT THE VARIATION,
SEMANTICS IN THE BRAIN, AT THE
SEMINAL LEVEL, AND AT THE TIME
SCALE OF ACTION POTENTIALS WHICH
WE'RE SPEAKING AND HEARING
REMAINS LARGELY UNKNOWN.
THIS BUILDING ON EARLIER WORK
BACK IN THE DAY USING fMRI TO
SHOW AREAS OF SEMANTIC
REPRESENTATIONS IN THE BRAIN.
NOW IT'S BEING BROUGHT DOWN TO
THE SINGLE CELL LEVEL.
SO USING MICROARRAY,
NEUROPIXELS, HIGH DENSITY
RECORDINGS, AWAKE INTRAOPERATIVE
PATIENTS CONSTRUCT MAPS OF
REALTIME LANGUAGE COMPREHENSION
ACROSS THE POSTERIOR MID-FRONTAL
GYRUS AND SHOWED REALLY VERY
ROBUST ACTIVITY OF SEMANTIC
REPRESENTATIONS OF NEURONS TO
BROAD CATEGORIES OF WORD
MEANING.
THEY CAN SHOW USING UNSTRUCTURED
WORD LIST TO DISTINGUISH THESE
FROM OTHER INPUTS, AND WHAT THEY
ARE ABLE TO FIND IS THAT THEY
CAN PROJECT THESE NEURONAL
TUNING TO HIGHER DIMENSIONAL
SPACE THAT REVEALS HIERARCHICAL
ORGANIZATION.
SO THESE FINDINGS ARE REALLY
COOL, FINELY DETAILED CORTICAL
ORGANIZATION OF SEMANTIC
REPRESENTATIONS AT THE
SINGLE-CELL LEVEL, MIND BLOWING,
BEGINS TO SHOW US ABOUT THE
CELLULAR LEVEL PROCESSING OF
MEANING OF LANGUAGE
COMPREHENSION, SO THIS IS, I
DON'T KNOW, TEN YEARS AGO WOULD
WE IMAGINE WE WOULD BE ABLE TO
GET THIS KIND OF INFORMATION?
I THINK NOT.
THIS IS REALLY SHOWING US WHAT
CAN BE DONE WITH NOT JUST
TECHNOLOGY BUT WITH REALLY
SOPHISTICATED ANALYSIS AND
DESIGNING A CLEVER EXPERIMENT.
SO STAY TUNED FOR THAT.
OKAY.
SO THE FINAL HIGHLIGHT I WANT TO
GO OVER WITH YOU, JUST CAME OUT.
THIS IS A STUDY FROM THE BRAIN
GATE CONSORTIUM.
THIS PRESENT STUDY WAS FUNDED BY
A SERIES OF GRANTS BY OUR
COLLEAGUES AT THE NATIONAL
INSTITUTE ON DEAFNESS AND OTHER
COMMUNICATION DISORDERS BUT I'LL
NOTE MUCH OF THE BRAIN GATE
TECHNOLOGIES WAS SUPPORTED BY
EARLY INVESTMENTS BY "BRAIN" SO
WE'RE VERY PROUD TO SEE THIS
GREAT SEAMLESS TRANSITION FROM
EARLY STAGE DEVELOPMENT BY
"BRAIN," THERE'S ALSO SUPPORT
FROM DARPA AND NSF AS IT MOVES
THROUGH INTO THE I.C.-SPECIFIC
MISSION.
NOW, HERE THEY HAVE DEVELOPED A
BRAIN-COMPUTER INTERFACE, SPEECH
PROSTHESIS.
I'VE HIGHLIGHTED SIMILAR THINGS
FROM VARIOUS GROUPS INCLUDING
BRAIN GATE SHOWING BCI, BRAIN TO
TEXT, BRAIN TO SPEECH.
THE RUB WITH THESE TECHNOLOGIES
THEY ARE STILL -- THIS IS STILL
A ONE-OFF BUT REQUIRE A LOT OF
TRAINING.
SO WE HAVE PATIENTS, HUMAN
BEINGS, THAT FOR VARIOUS REASONS
CANNOT COMMUNICATE, WHETHER
BECAUSE OF PARALYSIS DUE TO ALS,
SPINAL CORD INJURY, STROKE,
OTHER INJURIES, AND THEY ARE
LOCKED IN, A HORRIBLE CONDITION
TO BE N THEY WOULD GIVE ANYTHING
TO BE ABLE TO COMMUNICATE WITH
LOVED ONES, PART OF THEIR LIVES
BACK.
IF THIS REQUIRES EXTENSTIONIVE
STRANGE EVERY TIME YOU WANT TO
USE THIS IT'S GOING TO BE A BIG
BARRIER FOR DISSEMINATION.
SO, THE AMAZING THING HERE IS
THIS GROUP BY IMPLANTING FOUR
BASICICALLY UTAH ARRAYS IN THIS
ONE SUBJECT'S MOTOR CORTEX OVER
THE SPEECH AREAS, THEY WERE ABLE
TO BUILD A DECODER.
WE LEARNED A LOT ABOUT
ARTIFICIAL INTELLIGENCE AND
NEURONAL NETWORKS, INVOLVED
HERE, YOU CAN SEE ON THE BOTTOM,
TO READ OUT THE BRAIN ACTIVITY
AS THIS HUMAN RESEARCH PARTNER
IS TRYING TO SPEAK, AND PUTTING
THAT THROUGH SPEECH SYNTHESIZER
THAT INVOLVES, THIS IS THE CRAZY
PART, THEY TOOK VIDEO RECORDINGS
OF HIM BEFORE HE WAS UNABLE TO
SPEAK, HAVE THE SPEECH
SYNTHESIZER SPEAK IN HIS OWN
VOICE.
THIS IS AMAZING.
THIS IS HOW AMAZING IT REALLY
IS.
SO, THEY IMPLANTED THE
ELECTRODES, ABOUT 29 DAYS, 25
DAYS POST-OP, DID THE FIRST TEST
AND JUST GAVE HIM 50 WORDS ON A
SCREEN TO LITERALLY READ BACK.
AND IN THE FIRST SESSION, THEY
HIT ALMOST 100% ACCURACY.
CRAZY, RIGHT?
OVER THE NEXT 1.4 HOURS, 1.4
HOURS, THE NEXT SESSION THEY
WERE ABLE TO EXPAND VOCABULARY
SIGNIFICANTLY, RIGHT?
AND OVER BASICALLY TO GET 97 --
90+% ACCURACY, 95% ACCURACY
ALMOST RIGHT OFF THE BAT, OKAY?
125,000-WORD VOCABULARY, WITH
FURTHER TRAINING OUT TO 16 HOURS
OF TRAINING, JUST 16 HOURS OF
TRAINING, HE STABILIZED AT 97%
ACCURACY, AT 32 WORDS PER
MINUTE, 125,000-WORD VOCABULARY.
THIS RIVALS THE SPEECH TO TEXT
CONVERSION THAT YOU MIGHT HAVE
ON YOUR PHONE, QUITE REMARKABLE.
SO I WANT TO SHOW YOU TWO QUICK
VIDEOS, AND LITTLE WARNING HERE,
IF YOU HAVE A BOX OF TISSUES OR
HANDKERCHIEF GET THEM CLOSE BY.
THIS IS MOVING.
THE FIRST CLIP I'LL SHOW YOU IS
THE PARTICIPANT, THE RESEARCH
PARTNER, ON THE FIRST TRIAL
WHERE THEY SAID TRY READING
THESE 50 WORDS.
THEY HAD TO STOP THE TRIAL
BECAUSE EVERYBODY BROKE DOWN IN
TEARS, INCLUDING THE
INVESTIGATORS.
AND THEN IN THE SECOND CLIP A
LITTLE BIT OF COMMENTARY BUT
YOU'RE GOING TO HEAR HIM SPEAK
THROUGH THE SPEECH SYNTHESIZER,
SOUNDS LIKE IT'S A NARRATION
OVER THE VIDEO BUT IT'S THE --
IT'S MR. HAROLD ACTUALLY
SPEAKING THROUGH THIS SPEECH
SYNTHESIZER, AND HE WAS ACTUALLY
ABLE TO CONDUCT HIS WORK, HIS
WORK, HIS PROFESSIONAL WORK,
THROUGH ZOOM MEETINGS WITH THE
SYNTHESIZER.
HOPEFULLY THE SOUND WILL WORK.
IF IT DOESN'T SOMEBODY SCREAM
AND I'LL REBOOT IT.
OKAY, READY?
♪
>> A LOT OF THE DEMONSTRATIONS
OF BCI TECHNOLOGY OVER THE PAST
FEW DECADES TOOK WEEKS OR MONTHS
TO GET WORKING.
THE FIRST TIME HE TRIED TO USE
THE SYSTEM IT JUST WORKED.
OKAY.
READY?
THAT FIRST TIME HE TRIED TO
SPEAK AND THAT WORD APPEARED ON
THE SCREEN ...
HE STARTED CRYING, I STARTED
CRYING, HIS FAMILY STARTED
CRYING.
BASICALLY EVERYONE, WE HAD TO
PAUSE, STOPPED THE REST OF THAT
BLOCK OF EXPERIMENT TRIALS,
COMPOSED THEMSELVES.
ALL RIGHT, LET'S DO IT AGAIN.
IT KEPT WORKING.
SO, YEAH, IT WAS REALLY SPECIAL,
A SPECIAL MOMENT.
♪
PEOPLE WHO DO NOT HAVE THE
ABILITY TO COMMUNICATE WELL OR
QUICKLY ARE ISOLATED AND LONELY.
THIS WILL GIVE THEM HOPE AND
OPPORTUNITY TO BE MORE OF
THEMSELVES.
>> WE'RE AT A POINT WHERE IT
DOES WORK WELL ENOUGH THAT IT
LETS HIM BE A PART OF SOCIETY
AND TO TALK.
>> I AM ABLE TO STILL WORK FULL
TIME FOR CLIMATE ACTION, AND I'M
ABLE TO DO THAT WELL AND MORE
EFFICIENTLY WITH THIS DEVICE.
>> IT'S SO TRANSFORMATIVE
BECAUSE IT PROVIDES HOPE FOR
PEOPLE LIVING WITH THESE KINDS
OF DISEASES THAT AS THEY FACE
THEIR DISEASE, THEY KNOW THAT
THEY WILL HOPEFULLY HAVE THE
ABILITY TO RETAIN COMMUNICATION.
♪
>> SEE DR. - SO WE HAVE A LONG
WAY TO GO TO GET THESE
TECHNOLOGIES TO GIVE THEIR LIVES
BACK BUT ABILITY TO ESTABLISH
THESE IS LITERALLY PLUG AND PLAY
DEVICES I THINK IS A CRITICAL
FIRST STEP TOWARD THAT GOAL.
SO I'LL LEAVE IT AT THAT.
YOU CAN LEARN ABOUT US AT THE
USUAL PLACES.
AND I'M HAPPY TO TAKE QUESTIONS
>> NOT SEEING ANY HANDS YET.
>> AND I'M NOT CRYING, I DON'T
KNOW IF ANYBODY ELSE MIGHT BE.
>> OKAY, MAYBE WE SHOULD GO ON
TO GET THE UPDATE ON THE
NEUROETHICS WORKING GROUP.
CHRISTINE GRADY, ARE YOU HERE?
THERE SHE IS.
>> I AM HERE.
>> RIGHT.
>> I MIGHT BE CRYING THOUGH.
>> YEAH.
>> THAT WAS INCREDIBLY
IMPRESSIVE.
HOPE AND OPPORTUNITY.
SO, I'M CHRISTINE GRADY, I'M
HERE TO GIVE A SHORT REPORT ON
THE NEUROETHICS WORKING GROUP.
I'VE HAD THE PRIVILEGE OF
CO-CHAIRING THAT GROUP FOR
SEVERAL YEARS.
FOR THOSE NEW TODAY I'LL GIVE
TWO SECONDS OF WHAT THE
NEUROETHICS WORKING GROUP IS,
IT'S ABOUT TEN PEOPLE, SOME OF
WHOM ARE ON THIS CALL AND CAN
CORRECT ANYTHING I SAY THAT'S
NOT CORRECT.
I CO-CHAIR WITH DR. NITA
FARAHANY FROM DUKE, WE MIGHT
TWICE A YEAR, JANUARY AND
AUGUST, TOPICAL WORKSHOPS WHEN
APPROPRIATE.
THE NEUROETHICS WORKING GROUP IS
CHARGED WITH IDENTIFYING ETHICAL
CHALLENGES IN DEVELOPMENT OR
APPLICATION OF BRAIN RESEARCH
AND ANTICIPATING AND PROVIDING
WAYS FOR THE BRAIN INITIATIVE TO
NAVIGATE THESE CHALLENGES.
WE CAN PROVIDE ETHICS
CONSULTATION WHEN APPROPRIATE,
IDENTIFY QUESTIONS THAT MIGHT BE
AMENABLE TO NEUROETHICS RESEARCH
AND PUBLISH GUIDANCE ON KEY
ETHICAL CHALLENGES ASSOCIATED
WITH BRAIN.
YESTERDAY WE HAD AN EXCITING
MEETING WHERE WE FOCUSED ON THE
INTERSECTION OF ARTIFICIAL
INTELLIGENCE, NEUROSCIENCE, AND
ETHICS.
AND WE DID THAT BY EXPLORING TWO
CASE STUDIES.
BEFORE WE STARTED THE CASE
STUDIES WE HAD THREE SPEAKERS
WHO HELPED US SET THE STAGE.
DR. JOE MONACO FROM NINDS, DR.
DORIS TSAO FROM UC-BERKELEY, DR.
PATRICK MINAULT PROVIDING AN
OVERVIEW TO HELP US CONSIDER THE
ETHICAL ISSUES THAT MIGHT COME
FROM THAT SCIENCE.
THE FIRST CASE THAT WE HAD WAS A
DISCUSSION ABOUT DEEP
PHENOTYPING OF BRAIN DATA IN
MENTAL HEALTH AND PSYCHIATRY.
WE HAD TWO SPEAKERS, DR. JUSTIN
BAKER FROM HARVARD MEDICAL
SCHOOL, DISCUSSING HIS ONGOING
WORK IN WHICH A.I. MODELS TAKE
AS THEIR DATA INPUT MULTI-MODAL
MEASUREMENTS OF BRAIN AND
BIOLOGICAL VARIABLE ALSO IN
ORDER TO THEN PROVIDE ASSESSMENT
OF MENTAL HEALTH CONDITION OR
EVEN PREDICTION OF RESURGENCE OF
MENTAL HEALTH CONDITIONS.
THEN DR. BENJAMIN SILVERMAN FROM
MGH BRIGHAM PRESENTED AN ETHICS
CHECK LIST FOR RESEARCHERS DOING
THIS WORK TO HELP THEM CONSIDER
THE POTENTIAL CHALLENGES EARLY
IN THEIR PROCESS, AND THEN
ANOTHER PROJECT ON THE RETURN OF
INDIVIDUAL RESEARCH RESULTS TO
PARTICIPANTS IN THESE STUDIES.
HE MENTIONED SOME OF THE ETHICAL
CONSIDERATIONS RELATED TO
INFORMED CONSENT IN PSYCHIATRIC
CARE, PRIVACY AND CONFIDENTIAL,
EQUITY AND ACCESS, ALGORITHMIC
BIAS, AND RETURN OF RESULTS, AS
I'VE ALREADY MENTIONED.
THE SECOND CASE EXAMINED
GENERATIVE A.I. MODELS ON HUMAN
BRAIN DATA, AGAIN WE HAD TWO
SPEAKERS, HEARD FROM DR. KARIN
JERBI FROM UNIVERSITY OF
MONTREAL AND CANADIAN BRAIN
PROJECT PRESENTED A PROOF OF
PRINCIPLE GENERATIVE MODEL, GPT
MODEL, THAT US ON AS HUMAN EEG
DATA AS A TRAINING DATASET IN
ORDER TO MAKE FUTURE PREDICTIONS
ABOUT EEG DATA OUTPUT.
THEN DEBRA MATHEWS FROM JOHNS
HOPKINS UNIVERSITY RAISED
POTENTIAL ETHICAL CONSIDERATIONS
IN THIS PARTICULAR CASE, SOME OF
THE SAME ISSUES THAT WERE RAISED
IN THE FIRST CASE BUT ALSO THE
POTENTIAL FOR BIAS AND
DOWNSTREAM APPLICATION
DEVELOPMENT.
DR. MATTHEWS ALSO GAVE I THOUGHT
A VERY HELPFUL OVERVIEW OF SOME
OF THE ONGOING A.I. GOVERNANCE
AND ETHICAL FRAMEWORKS WHICH ARE
OUT THERE AND BECOMING MORE
POPULAR, AND WHICH HELPED TO
HIGHLIGHT WHAT CURRENTLY EXISTS
IN THE FIELD AND WHAT'S LEFT AT
THE NEUROETHICS GROUP MIGHT BE
ABLE TO MAKE -- HOW THE WORKING
GROUP MIGHT BE ABLE TO MAKE A
UNIQUE CONTRIBUTION.
WE TALKED ABOUT NEXT STEPS FOR
NEWG, WHICH IS SHORT HAND FOR
THE NEUROETHICS WORKING GROUP.
AND PARTICULARLY RECOGNIZING THE
SPEED AT WHICH THE SCIENCE IS
MOVING, HOW TO SORT OF THINK
ABOUT CREATING THE ETHICAL
FRAMEWORKS THAT WILL BE USEFUL
AS SCIENCE EVOLVES SO RAPIDLY.
SOME THINGS WE THOUGHT ABOUT
WHETHER CONSIDER WHAT MIGHT BE
UNIQUE AT THE INTERSECTION OF
BRAIN RESEARCH AND A.I., AND
WHAT MIGHT BE SORT OF PARALLELS
TO OTHER FIELDS AND OTHER
ETHICAL GUIDANCE AND FRAMEWORKS
AND LITERATURE THAT WE HAVE.
WE TALKED ABOUT QUESTIONS ABOUT
INSCRUTABILITY AND SCALE, AS THE
MODELS AND DATASETS CONTINUE
TENNESSEE CREASE IN SIZE AND
COMPLEXITY.
AND THE TRADEOFFS THAT HAVE TO
BE MADE BETWEEN REQUIREMENTS FOR
A.I. MODEL AND ITS OUTPUT.
WE TALKED ABOUT WHAT MIGHT BE
UNIQUE IN THIS SPACE ABOUT
ALGORITHMIC BIAS, ESPECIALLY
THINKING ABOUT WHAT STRATEGIES
MIGHT BE USED FOR MITIGATING
SUCH BIAS IN BRAIN DATA TRAINING
DATA.
AND IN THE PIPELINE.
AND THEN WE STARTED TO TALK
ABOUT WHAT THE NEUROETHICS
WORKING GROUP MIGHT BE ABLE TO
DO IN THIS AREA GOING FORWARD,
INCLUDING MAYBE THINKING ABOUT
POINTS TO CONSIDER OR GUIDING
PRINCIPLES, AND INVENTORY OF THE
A.I. WORK AND A.I. ETHICS WORK
THAT'S HAPPENING ACROSS THE NIH,
AND MAYBE A FOCUSED WORKSHOP AT
SOME TIME IN THE FUTURE.
WE ALSO RECOGNIZE THERE'S A LOT
GOING ON IN THIS SPACE, AND SO
WE WANT TO SORT OF TAKE STOCK OF
THAT BEFORE WE JUMP IN AND
REPEAT WHAT OTHERS HAVE DONE.
SO, THIS MEETING OF COURSE, THE
MEET WE GO HAD YESTERDAY,
COMPLEMENTS ONGOING EFFORTS
INCLUDING THERE WAS A RECENT
NATIONAL ACADEMIES WORKSHOP ON
A.I. AND NEUROSCIENCE, A
FORTHCOMING, NEUROA.I. WORKSHOP
THAT THE NIH IS COMING ON IN
NOVEMBER.
AND THE INTERNATIONAL
NEUROETHICS MEETING IN THE
SPRING WILL ALSO BE FOCUSING ON
A.I., NEUROSCIENCE, ETHICS.
SO THERE'S A LOT GOING ON IN
THIS AREA.
AND WE WANT TO CONTINUE TO BE
USEFUL IN THIS SPACE AND SO I'M
SURE YOU'LL HEAR FROM US IN THE
FUTURE WHAT THE NEWG MIGHT BE
DOING IN THIS INTERACTION OF
NEUROSCIENCE AND A.I.
THAT'S ALL.
IF ANYBODY HAS ANY -- IN
NEUROETHICS WORKING GROUP
MEMBERS HAVE ANYTHING TO ADD,
PLEASE DO.
I'M HAPPY TO ANSWER ANY
QUESTIONS.
I WILL SAY THE POTENTIAL THAT
THAT STUDY THAT YOU SHOWED, THE
LAST STUDY THAT YOU SHOWED,
JOHN, FOR, YOU KNOW, HELPING
PEOPLE RAISES SO MUCH PROMISE.
BUT THERE ARE GOING TO BE
ETHICAL ISSUES AROUND THAT AS
WELL.
THERE ARE.
>> OH, ABSOLUTELY.
I MEAN, THERE'S SO MANY, SO, SO
MANY, INCLUDING ACCESS, RIGHT?
>> TOTALLY, ACCESS BEING ONE THE
BIG ONES.
>> YES.
BUT THESE ARE GREAT CHALLENGES
FOR US TO SOLVE ON THE WAY TO
GETTING THESE THINGS OUT TO HELP
PEOPLE, YEAH.
>> ABSOLUTELY.
THANKS FOR LISTENING TO ME, I'M
SORRY I DIDN'T HAVE SLIDES LIKE
JOHN DID.
FANCY GRAPHICS.
>> I GOT A MACHINE BEHIND ME
TOO.
AND WE JUST HAD THE MEETING
YESTERDAY.
THANKS, CHRISTINE AND NINA AND
SASKIA HENDRIKS ALSO FOR PUTTING
THIS TOGETHER.
IT WAS A GREAT AND REVEALING
SESSION.
AS WE TALKED ABOUT, IT'S JUST
GOING TO BE, YOU KNOW, ONE PIECE
OF OUR GROWING INTEREST, IN A.I.
AND HOW IT INTERSECTS WITH WHAT
WE DO IN BRAIN AND NEUROSCIENCE
MORE GENERALLY AS A
BIDIRECTIONAL CONCERN.
OKAY.
SO LET'S SEE.
I THINK WE HAVE A LITTLE BIT OF
TIME IF PEOPLE HAVE QUESTIONS
EITHER FOR CHRISTINE OR FOR
MYSELF.
BEFORE WE MOVE ON TO TIRIN'S
PRESENTATION.
ANYBODY?
OKAY.
TIRIN, ARE YOU READY FOR YOUR
TOPIC?
WHAT WE TRY TO DO AT SOME OF
THESE MEETINGS IS HAVE A
SCIENTIFIC PRESENTATION FROM ONE
OF OUR MCWG MEMBERS, ALL YOU
FOLKS ARE LEADERS IN YOUR
RESPECTIVE FIELDS, A GREAT
OPPORTUNITY TO LEARN ABOUT WHAT
YOU'RE DOING.
DR. MOORE IS PROFESSOR OF
NEUROBIOLOGY, HMMI INVESTIGATOR
AT STANFORD, THANK YOU FOR ALL
THAT YOU DO FOR US.
HIS LAB STUDIES NEURAL
MECHANISMS OF VISION AND MOTOR
INTEGRATION, NEURAL BASIS OF
COGNITION, IN OTHER WORDS
ATTENTION.
AND HIS GROUP STUDIES ACTIVITY
OF SINGLE NEURONS IN VISUAL
MOTOR STRUCTURES IN THE BRAIN,
HOW IT AFFECTS PERCEPTION AND
MOTOR PERFORMANCE OF BEHAVING
ANIMALS.
TIRIN, YOU'VE EXPRESSED
EXCITEMENT ABOUT THE
POSSIBILITIES NOW THAT THE HIGH
DENSITY ELECTRODES THAT ALLOW US
REALLY TO LOOK AT, YOU KNOW,
TRUE NETWORKS AND ACTIVITY.
I HOPE YOU'RE GOING TO SHARE
THAT WITH US.
>> YES.
>> EXCELLENT.
AND HE'S OF COURSE BEEN
RECOGNIZED FOR HIS MANY
CONTRIBUTIONS, TOO MANY FOR ME
TO MENTION HERE, ELECTED MEMBER
OF THE NATIONAL ACADEMY OF
SCIENCES, NATIONAL ACADEMY OF
MEDICINE, AMERICAN ACADEMY OF
ARTS AND SCIENCES, GOT HIS
Ph.D. FROM PRINCETON
UNIVERSITY, HE'S BAY AREA
NATIVE, OAKLAND, CALIFORNIA, AND
NOW MOVED SOUTH TO STANFORD AND
GOT HIS POSTDOC AT M.I.T.
TIRIN, ALL YOURS.
WE'RE EXCITED TO HEAR ABOUT YOUR
WORK.
>> OKAY.
LET ME SEE IF THIS WORKS.
YOU SHOULD SEE MY TITLE SLIDE
HOPEFULLY.
>> PERFECT, THANK YOU.
>> OKAY.
YEAH, ALL RIGHT.
SO, I WANT TO TALK ABOUT A TOPIC
THAT MY LAB SORT OF RECENTLY
KIND OF WANDERED INTO ALMOST
INADVERTENTLY.
OOPS, DID I JUST STOP THE SHARE?
>> YOU DID.
>> I WAS TRYING TO GET RID OF
THAT STUPID -- THERE'S THAT ZOOM
SHARE BUTTON IN MY WAY.
I COULDN'T SEE.
DID I -- OKAY.
>> YOU'RE GOOD.
DON'T TOUCH ANYTHING.
>> WHAT WAS THAT?
>> YOU'RE GOOD, IT'S PERFECT.
>> ,
>> YEAH, WE WANDERED INTO THIS
AREA, WORK THAT'S BEEN ENABLED
BY RECENT DEVELOPMENT OF LARGE
SCALE HIGH DENSITY NEURAL
RECORDINGS IN PRIMATES AND
MONKEYS, AS JOHN ALLUDED TO,
I'LL TALK ABOUT THAT AND ABOUT
HOW IT ENABLES TO ADDRESS
FUNDAMENTAL ISSUES NEW
NEUROSCIENCE.
RIGHT.
SO THE TOPIC CONCERNS THE ROLE
OF PREFRONTAL CORTEX, SPATIAL
MEMORY, TIME I HAVE I WANT TO
TALK ABOUT LARGE SCALE IN
MONKEYS AND IN GENERAL, HOW ITS
ENABLED US TO DO A LOT.
ABOUT SOME NEW RESULTS ENABLED
BY RECORDINGS.
THE CODING OF SPATIAL WORKING
MEMORY, SO WORKING MEMORY, YOU
KNOW, ENABLES TEMPORARY STORAGE,
ET CETERA, CRUCIAL FOR EXECUTION
OF TASKS.
NEURONS IN PREFRONTAL CORTEX
KNOWN TO PLAY A CRITICAL CONTROL
IN WORKING MEMORY INCLUDING
SPATIAL, TEMPORARY STORAGE ABOUT
SPATIAL LOCATIONS.
THIS IS FROZEN ON ME.
THAT'S NOT GOOD.
HERE WE GO.
OKAY, YEAH.
ALL RIGHT.
SO IT'S WELL KNOWN MACAQUE
MONKEYS IS A GREAT MODEL FOR A
LOT OF THINGS CERTAINLY THE
VISUAL SYSTEM BUT FUNDAMENTAL
BASIC COGNITIVE TASKS.
THEY ARE GOOD AT PERFORMING THE
SAME TYPES OF WORKING MEMORY
TASKS HUMANS FORM, BASIC FORM.
FOR EXAMPLE, SIMPLEST AND MOST
WELL KNOWN IS DELAYED RESPONSE
TASK, SPATIAL WORKING MEMORY
TASK.
A TASK THE MONEY FIXES A GAZE
CENTRALLY, THERE'S A CUE, VISUAL
CUE, PRESENTED IN SPACE, THE
ANIMAL HAS TO MEMORIZE DURING A
DELAY PERIOD AND AT THE END OF
THE PERIOD HAS TO RENDER A
RESPONSE, IN THIS CASE OCULAR TO
INDICATE WHERE THE CUE USED TO
BE.
EXPLOITING THIS WELL ESTABLISHED
PARADIGM WE LEVERAGED BENEFITS
OF LARGE SCALE NEURAL
RECORDINGS, TO ADDRESS
LONGSTANDING QUESTION REGARDING
NEURAL BASIS OF SHORT-TERM
WORKING MEMORY, SPECIFICALLY WE
TRIED TO RECONCILE TWO COMPETING
MECHANISTIC MODELS OF WORKING
MEMORY.
WHAT ARE THEY?
FIRST MODEL IS THE TEXT BOOK
MODEL, THE SPIKING MODEL FOR
SIMPLICITY.
IN THIS KALES INFORMATION HELD
IN WORKING MEMORY STOREDDED BY
SPIKING ACTIVITY OF NEURONS
ASSOCIATED WITH PARTICULAR
MEMORY CUE.
SO THE CUE.
SO THE SPATIAL CUE IN THE
PREVIOUS EXAMPLE.
SO, FOLLOWING A PERIOD OF
QUIESCENCE AT THE BEGINNING OF
EACH BEHAVIORAL TRIAL THE MEMORY
CUE EVOKES A PATTERN OF ACTIVITY
AMONG NETWORK OF NEURONS, TRULY
DEPICTED IN THIS CARTOON HERE.
AND DURING THE MEMORY DELAY
PERIOD THAT ACTIVITY PERSISTS
AND CONTINUES TO SIGNAL
MEMORANDUM, MOST OF YOU KNOW,
MANY OF YOU KNOW AT LEAST,
PERSISTENT ACTIVITY, PERSISTENT
DELAY PERIOD OF SPIKING ACTIVITY
OBSERVED THROUGHOUT MACAQUE
BRAIN FIRST DESCRIBED IN THE
'70s.
IN THE SECOND SORT OF LESS
WELL-KNOWN MODEL, THE SYNAPTIC
MODEL, THAT MODEL INFORMATION
HELD IN WORKING MEMORY STORED BY
PATTERN OF SHORT-TERM PLASTIC
CHANGES INITIATED BY PARTICULAR
MEMORY CUE.
SO FOLLOWING FIXATION PERIOD IN
THE PREVIOUS TEST, MEMORY CUE
EVOKES PATTERN ACTIVITY AMONG
NETWORK OF NEURONS AS WELL AS
DISTINCT PATTERN OF SHORT-TERM
PLASTICITY, BETWEEN THESE NODES,
WHICH TEMPORARILY AUGMENT
CONNECTIVITY AMONG
CUE-ASSOCIATED NEURONS.
DURING THE MEMORY DELAY PERIOD
EVEN IN THE ABSENCE OF ANY
PERSISTENT SPIKING ACTIVITY,
REMEMBERING INFORMATION
NONETHELESS PERSISTS IN DISTINCT
PATTERNS OF UNIQUE CONNECTIVITY.
UNIQUE ENSEMBLES.
UNLIKE EVIDENCE FOR PERSISTENT
SPIKING ACTIVITY WHICH IS EASIER
TO OBSERVE DIRECTLY, EVIDENCE IN
SUPPORT OF SYNAPTIC MODEL IS
LESS STRONG.
HOWEVER, AS WE'LL SEE THERE ARE
CLEAR ISSUES WITH EVIDENCE FOR
THE FIRST MODEL.
ALL RIGHT.
AS I MENTIONED PERSISTENT
ACTIVITY HAS BEEN OBSERVED
DURING THE DELAYED PERIOD OF
WORKING MEMORY TASK FOR QUITE
SOME TIME, PRE-FRONT CORTEX IN
MANY OTHER AREAS.
FOR EXAMPLE WE CAN MEASURE THE
ACTIVITY OF NEURONS IN THE
DLPFC, AND THESE ARE THREE
EXAMPLE NEURONS RECORDED AT
LATERAL PREFRONTAL CORTEX, THIS
REPRESENTS ACTIVITY FOLLOWING
PRESENTATION OF ONE OF THE CUES.
HERE WE HAVE NEURON THAT
RESPONDS TO THE CUE, AND
ACTIVITY PERSISTS, DEPENDENT
UPON WHERE THE CUE WAS, HERE
THERE'S NO CUE RESPONSE BUT
STILL ACTIVITY THAT DEPENDS
WHERE THE CUE WAS.
HERE MINIMAL RESPONSE BUT CLEAR
TUNING OF LOCATION OF THE
REMEMBERED CUE, THAT'S THE
CLASSIC RESULT.
AT LEAST THIS IS TRUE IF WE'RE
LOOKING AT THE ACTIVITY THAT'S
AVERAGED OVER MANY TRIALS.
HOWEVER SEVERAL STUDIES NOTED
DELAYED PERIOD ACTIVITY IS
NOISIER ON SINGLE TRIALS, CALLS
INTO QUESTION UTILITY OF
PERSISTENT SPIKING ACTIVITY AS
RELIABLE MECHANIC MECHANISM FOR
MEMORIAL RIP MAINTENANCE.
EVEN IF THERE ARE MOMENTARY
LAPSES, COMPENSATES, YOU CAN
HAVE THE SORT OF, YOU KNOW,
JOINT OR SORT OF DIFFERENT
NEURONS COMING ON AND OFF TO
BRIDGE THE GAP BETWEEN LAPSES
BETWEEN INDIVIDUAL NEURONS.
SO THAT COULD BE TRUE BUT TO
OBSERVE THAT POSSIBILITY OR RULE
IT OUT YOU HAVE TO
SIMULTANEOUSLY RECORD THE
ACTIVITY OF A LARGE LOCAL
POPULATION OF NEURONS, IN A
DIRECTLY MEASURED STABILITY OF
MEMORANDUM INFORMATION WITHIN
THAT POPULATION.
ALL RIGHT.
SO THERE'S A MAJOR OBSTACLE, THE
MEASUREMENT GAP.
WE NEED TO BE ABLE TO MEASURE
ACTIVITY OF LARGE LOCAL
POPULATIONS OF NEURONS THAT WE
NEW ENGLAND ARE -- WE THINK ARE
INVOLVED IN WORKING MEMORY ON
SINGLE TRIALS.
THAT WOULD ALLOW US TO MEASURE
STABILITY AND PERSISTENCE OF
MEMORY INFORMATION DURING MEMORY
DELAY PERIOD.
ALL RIGHT.
SO, AMONG THE MANY TOOLS THAT
ARE AVAILABLE IN NEUROBIOLOGY
PERHAPS THE ONE MOST READILY
AVAILABLE AND IDEALLY SUITED FOR
NON-HUMAN PRIMATE, LARGE SCALE
HIGH DENSITY EFI DIS
THE NEUROPIXEL PROBES,
INTRODUCED EIGHT YEARS AGO.
THESE PROBES PACK ABOUT A
THOUSAND CHANNELS PER
CENTIMETER, THIS IS THE RODENT
PROBE, 1 CENTIMETER SHANK, A
THOUSAND CONTACTS, A THIN PROBE,
DATA REPORTED IN MACAQUE V1.
THESE ARE THE WAVEFORMS OF
INDIVIDUAL NEURONS PLOTTED AT
APPROXIMATED LOCATIONS RELATIVE
TO CONTACTS OF THE ELECTRODE SO
THE POINT BEING YOU CAN CAPTURE
THE --
>> TIRIN, WE --
>> IN A SMALL VOLUME.
>> WE'VE BEEN -- YOUR VOICE HAS
BEEN GLITCHY, DO YOU WANT TO TRY
WITHOUT YOUR VIDEO ON?
THAT MIGHT HELP.
>> SURE.
>> WE LOST YOUR SCREEN.
NOW WE LOST YOUR --
>> I KNOW.
>> OKAY.
>> IS IT BETTER NOW?
SOUND IS OKAY?
>> YES.
HELLO?
>> YES, CAN YOU HEAR US?
TIRIN?
>> OKAY, I CAN HEAR YOU, YEAH.
SORRY.
YES?
>> THE SOUND IS GOOD.
WE LOST YOUR SCREEN AGAIN.
>> WI-FI IS SKETCHY.
>> WE SEE YOUR SLIDES.
>> OH, WOW.
>> NO.
>> OKAY, YOU STILL HEAR ME?
SORRY, THE WI-FI IS SKETCHY
WHERE I AM.
>> OKAY.
>> LET ME TRY TO --
>> WE CAN HEAR YOU NOW AND SEE
THE SLIDES.
>> OKAY, ALL RIGHT.
THANKS A LOT.
IF IT HAPPENS AGAIN LET ME KNOW.
>> OKAY.
>> YEAH, SO ANYWAY, OKAY.
HOPEFULLY YOU CAN HEAR ME.
ANYWAY, SEVERAL YEARS AGO WE
TESTED OUT THESE NEW NEURAL
PIXEL -- HELLO?
WE'RE GOOD?
>> WE HEAR YOU.
>> YOU'RE GOOD.
KEEP GOING.
>> OKAY.
YEAH, WE TESTED OUT NEURAL PIXEL
PROBES TO ADAPT FOR USE IN
NON-HUMAN PRIMATES, THIS BEGAN
SEVERAL YEARS AGO.
SO FOR EXAMPLE WE LOOK AT HERE
SOME RECORDINGS MACAQUE V1
SHOWING THIS SLICE IN MACAQUE
V1, WE DIPPED SOME PROBES IN DYE
DERIVATIVE LOOKING AT ELECTRODE
TRACK.
CURRENT SOURCE DENSITY RECORDED
ACROSS A SINGLE COLUMN OF
MACAQUE V1 TO ESTIMATE LAMINAR
COME PART OF THE BOUNDARIES,
LAYER 4 HERE BASED ON THE
SOURCES.
HERE WE HAVE SPIKE WAVEFORMS OF
ROUGHLY 200 NEURONS, PLOTTED AS
A HEAT MAP SO YOU CAN SEE
DIFFERENT LENGTHS ARE LONGER,
LAYER 5 AS YOU'D EXPECT.
ON THE RIGHT SIDE YOU SEE --
EACH ROW IN THIS PLOT, HOT PLOT,
IT'S SHOWING THE ACTIVITY OF
NEURONS IN RESPONSE TO A
DRIFTING GRADING OF ORIENTATION
ACROSS ORIENTATIONS.
AND SO YOU CAN SEE THERE ARE TWO
PEAKS FOR SAME ORIENTATION, SO
THIS IS -- EACH ROW IS A
RESPONSE, RESPONSE ON THE Z AXIS
ACROSS LAYERS OF A SINGLE COLUMN
OF V1, ORIENTATION COLUMN IN
MACAQUE V1 SO YOU CAN SORT OF
SEE THAT QUITE CLEARLY FROM THE
SINGLE RECORDING.
ALL RIGHT.
SO, WE WERE -- ONE OF THE MANY
BENEFITS OF THESE HIGH DENSITY
RECORDINGS ALSO DRAMATICALLY
INCREASES CAPACITY TO ASSESS
AMOUNT OF CO-VARIATION AND
SPIKING ACTIVITY OF LARGE
POPULATIONS OF LOCAL NEURONAL
NETWORKS, INVOLVED IN THE SAME
NETWORKS.
SO WITH SUCH HIGH DENSITY
NEURONS WE CAN MEASURE
DYSFUNCTIONAL CONNECTIVITY OF
PAIRS IN THE SAME CORTICAL
COLUMN, SO WE CAN DO SOME
CROSS-CORRELATION ANALYSES QUITE
STANDARD BUT -- I'LL SKIP
DETAILS BUT THE IMPORTANT THING
IS THE NUMBER OF PAIRS, NUMBER
OF PAIRINGS OF NEURONS CONNECTED
AT LEAST FUNCTIONALLY ALLOWS YOU
TO -- GIVES SO MUCH POWER TO
EXTRACT LARGE NUMBERS OF PAIRS
OF NEURONS THAT ARE INVOLVED IN
THE SAME NETWORKS.
SO, FOR EXAMPLE THESE ARE TWO
NEURONAL PAIRS, SORRY.
OKAY, YEAH.
CROSS-CORRELATION OF PAIR 1,
PAIR 2, DIFFERENT ONLY SLIGHTLY
IN VERTICAL DISTANCE BUT THE
TIME LAG AND CROSS-CORRELATION
FUNCTIONS, PAIR 1 AND PAIR 2,
BEARS OUT THE FACT ONE PAIR IS
CLOSER THAN THE OTHER PAIR SO IF
YOU LOOK AT SIMPLE THINGS LIKE
THE TRADEOFF FUNCTIONS BETWEEN
THE EFFICACY OF
CROSS-CORRELATION OR TIME LAG,
IT'S A LAWFUL RELATIONSHIP
BETWEEN THAT AND THE DISTANCE
BETWEEN THE NEURONS EVEN IN THE
SAME -- IN THE COLUMN CORTEX,
THAT'S REALLY POWERED BY THE
FACT YOU HAVE SO MANY NEURONS IN
THE SAME LOCAL NETWORK.
NOT SO MUCH THE LARGE NUMBERS OF
NETWORKS, IT'S THE HIGH DENSITY
OF NEURONS.
WE'LL COME BACK WITH THE
SCIENTIFIC QUESTION THAT WE
ADDRESS, THE ORIGINAL QUESTION I
ALLUDED TO.
THIS IS SHOWING ALSO IF YOU LOOK
AT THE CROSS-CORRELATION
FUNCTIONS ACROSS THOUSANDS OF
PAIRS OF NEURONS YOU GET
TEMPLATES AND
CROSS-CORRELATIONS, SHARPLY
SYNCHRONOUS, PUTATIVE FORWARD,
PUTATIVE BACK.
FOR EXAMPLE, IN LOOKING AT
STRUCTURE LIKE V1, YOU GET
INPUTS FROM THE THALAMUS IN
LAYER 4, 4C, THAT YOU WOULD
EXPECT YOU COULD GET A LOT OF
NEURONS CORRELATED WITH SHORT
TIME LAGS LIKE VERY SHARP
SYNCHRONIES BECAUSE YOU'RE
GETTING SYNCHRONOUS INPUTS FROM
THE THALAMUS SO THERE SHOULD BE
HIGHER PROPORTION OF THIS TYPE
OF CONNECTION, EXACTLY WHAT YOU
FIND, NEURONS IN LAYER 4C, 4C
PAIRS, SORRY, 4C ALPHA OR BETA
PAIRS IN LAYER 6, THALAMIC
INPUT, DISPROPORTIONATE NUMBERS
OF NEURONS.
WE CAN SORT OF USE THAT TO SORT
OF REALIZE WHAT WE MIGHT BE ABLE
TO LEARN FROM STRUCTURES THAT WE
HAVE NOT -- THAT WE DON'T KNOW
AS MUCH ABOUT IN THE MONKEY
BRAIN.
ALL RIGHT.
SO, THESE NEURAL PIXEL PROBES
ALLOWED RECORDINGS ACROSS MOST
OF THE MACAQUE BRAIN, NEED TO BE
SCALED SHOWING THIS LITTLE
CARTOON, 4 1/2 CENTIMETERS
INSTEAD OF 1 CENTIMETER, WIDER,
THESE PROBES.
THIS IS ONE SHOWN IN SOMEONE'S
GRASP.
MORE BANKS OF ELECTRODES, 4 1/2
THOUSAND CONTACTS FROM WHICH YOU
CAN ACTIVELY RECORD, AND 1.0
VERSION THERE'S NOW GOING TO BE
A 3.0 VERSION IN A COUPLE YEARS
YOU CAN RECORD 1 1/2 THOUSAND,
AT THE SAME TIME, AND IT WILL
HAVE 6,000 CONTACTS.
RIGHT.
HERE IS AN EXAMPLE RECORDING
THAT'S DONE IN MY LAB FROM --
HERE I'M SHOWING SAGITTAL
SECTION OF MACAQUE CEREBRAL
CORTEX, COLOR BITS ARE THE AREAS
OF THE MACAQUE VISUAL CORTEX
WHERE YOU HAVE MULTIPLE
REPRESENTATIONS OF THE
CONTRALATERAL VISUAL FIELD, AND
YOU CAN, YOU KNOW, OF COURSE
MANY OF THE AREAS HAVE
HISTORICALLY BEEN RECORDED FROM
WITH VERY LOW CHANNEL
ELECTRODES, UP TO 15 OR 16,
SORRY, MEASURE 16 OR 32, EXCUSE
ME.
HERE SHOWING A RECORDING DONE,
YOU KNOW, ACROSS ABOUT I
THINK -- YES, 16 MILLIMETERS,
THROUGH MULTIPLE REPRESENTATIONS
OF THE VISUAL FIELD, I'VE SHOWN
HERE FIVE BANKS OF ELECTRODES
BOTH -- EACH 384 CHANNELS, HERE
WE HAVE THE WAVEFORMS SHOWN
AGAIN MAPPED ON THE ROUGH
LOCATION, ANATOMICALLY, ON THE
PROBE.
SO 3,000 WAVEFORMS, SINGLE
NEURONS, SHOWING YOU THE VISUAL
RESPONSE OF THE NEURONS TO A
SINGLE STIMULUS ON THE SCREEN
AND ITS RECEPTOR FIELD, EXCUSE
ME, ACROSS FIVE BANKS.
FIVE BANKS WERE RECORDED IN
DIFFERENT BLOCKS OF TRIALS
BECAUSE YOU CAN ONLY RECORD 384
IN EACH BANK, YOU CAN'T DO THEM
SIMULTANEOUSLY.
SO GOING ACROSS THESE 16
MILLIMETERS, WHAT WE SEE IS YOU
CAN SEE SOMETHING RATHER
IMPRESSIVE, ABILITY TO LOOK AT
MULTIPLE REPRESENTATIONS ACROSS
MACAQUE VISUAL CORTEX.
EACH LITTLE WINDOW HERE IS
RECEPTOR FIELD MAPPED OF A
SINGLE NEURON, SHOWING A NEURON
THAT RESPONDS WITH THE
HORIZONTAL MERIDIAN.
YOU CAN SEE PROGRESSION IN THE
RECEPTOR FIELD ON VISUAL
REPRESENTATION THAT WE KNOW
OCCURS IN THESE DIFFERENT VISUAL
AREAS AND TRANSITIONS BETWEEN
VISUAL AREAS.
AND IT'S REALLY JUST A LOOK AT
THE VISUAL SYSTEM THAT WE'VE
BEEN WORKING ON FOR A LONG TIME,
NEVER GET TO SEE, UNBELIEVABLE.
SO THIS IS A GREAT EXAMPLE OF
HOW THESE LARGE SCALE HIGH
DENSITY PROBES REALLY ARE
REVOLUTIONIZING PHYSIOLOGY,
PARTICULARLY NON-HUMAN PRIMATES.
ALL RIGHT.
LET'S GO BACK TO THE SCIENTIFIC
QUESTION I RAISED.
THERE WE GO.
OKAY, YEAH.
ALL RIGHT.
WE LEVERAGE BENEFITS OF THESE
NEURAL PIXEL PROBES, NON-HUMAN
PRIMATE PIXEL PROBES TO ADDRESS
THE QUESTION OF WORKING MEMORY.
SPECIFICALLY TRY TO RECONCILE
TWO COMPETING MODELS I TALKED
ABOUT.
OKAY.
IT'S WELL KNOWN MACAQUE MONKEYS
ARE GOOD AT PERFORMING THE SAME
TASK, AS I MENTIONED BEFORE.
AND SO, WE'RE USING THOSE
PROBES, ENABLED US TO MEASURE
THE STABILITY OF MEMORY
INFORMATION AND LARGE LOCAL
POPULATIONS, LATERAL PFC.
ON THE RIGHT WE'VE GOT
RECORDINGS BY MY POSTDOC MATT,
RECORDINGS IN LATERAL PFC, AS I
WAS SHOWING BEFORE INDIVIDUAL
WAVEFORMS OF NEURONS RECORDED
WITH THIS NHP PROBES, ABOUT
HUNDREDS OF NEURONS RECORDED
SIMULTANEOUSLY.
AND PRETTY SMALL 4-MILLIMETER
ROUGHLY PATCH OF CORTEX, HIGHLY
DENSE POPULATION OF NEURONS.
ALL RIGHT.
SO, BY THE WAY THE NEURONS SHOWN
IN BURGUNDY COLOR ARE NEURONS
THAT HAVE ACTIVITY IN THE MEMORY
PERIOD OF THAT TASK THAT I
DESCRIBED EARLIER.
INDIVIDUALLY SHOW DELAY PERIOD
ACTIVITY, LOTS OF MEMORY OF
QUOTE/UNQUOTE MEMORY NEURONS.
SO FROM HIGH DENSITY RECORDINGS
WE CAN CONVENIENTLY MEASURE
INFORMATION IN THE POPULATION
THAT'S AVAILABLE IN SPIKING
ACTIVITY OF THAT POPULATION
DURING THE MEMORY PERIOD.
FOR EXAMPLE WE CAN TRAIN DECODER
TO CLASSIFY POPULATION BELONGING
TO ONE OF TWO POSSIBLE TRIALS.
IN THIS CASE WHERE A CUE WAS
HERE OR THERE, USING STANDARD
DECODING METHODS, TEST THE
IDENTITY OF THE RESPONSE OF THE
HELD-OUT TRIAL.
IF YOU LOOK AT THE PERFORMANCE
OF OUR BINARY CLASSIFIER DURING
THE CUE, SUBSEQUENT DELAY
PERIOD, YOU FIND THE AVERAGE
PERFORMANCE OF YOUR DECODER
TRAINED ON THE POPULATION
ACTIVITY IS, YOU KNOW,
ACCURATELY DECODING LOCATION OF
THE INITIAL CUE STIMULUS, MEMORY
PERIOD HERE, RIGHT?
BUT THAT, YOU KNOW, THAT AS
WELL -- OKAY, BLACK HERE IS --
THE BLACK LINE HERE IS THE MEAN
CLASSIFIER PERFORMANCE ACROSS
ALL OF 18 RECORDING SESSIONS,
TWO ANIMALS.
GRAY LINES SHOW AVERAGE
PERFORMANCE FOR EACH INDIVIDUAL
SESSION.
BUT, YOU KNOW, OF COURSE AGAIN
THIS IS A TRIAL AVERAGED RATE OF
FIRING, CLASSIFIER PERFORMANCES
DERIVED FROM DATA AVERAGED
ACROSS TRIALS.
WHAT WE WANT THOUGH IS TO
MEASURE RELIABILITY OF THAT
SIGNAL ACROSS THE DELAY ON
SINGLE TRIALS, RIGHT?
SO TO MEASURE THE SINGLE TRIAL
INFORMATION WE USE THE
CONFIDENCE AND CLASSIFIER, THAT
IS PROBABILITY OF A CORRECT
CHOICE OF DECODING, DECODER FOR
ANY SET OF SPIKING ACTIVITY
GIVEN THE DATA THAT IT'S TRAINED
ON.
THEN WE CAN EXAMINE DYNAMICS
THROUGHOUT EACH OF THE TRIALS,
IN EACH RECORDING SESSION.
AND SO, HERE, OKAY, HERE'S AN
EXAMPLE SET OF TRIALS, THE HOT
MAP FROM ONE SESSION, ONE
ANIMAL, A HEAT MAP, HIGH
CONFIDENCE SHOWN IN THE SORT OF
ORANGE.
AND THEN LOW CONFIDENCE OR NEAR
CHANCE CONFIDENCE IN BLUE.
AND TRIALS ARE SHOWN IN STACKED
ORDER.
EACH OF THESE, TRIAL 1 TO TRIAL
N.
YOU CAN SEE WE WERE STRUCK AND
SURPRISED BY THIS AT THE START
CONFIDENCE IS HIGH, VISUAL
RESPONSE TO THE CUE.
AND SO HIGH CONFIDENCE WHERE THE
CUE IS, BECAUSE IT'S ON THE
SCREEN.
BUT THEN SHORTLY AFTER THE CUE
DISAPPEARS, CONFIDENCE IN THE
LOCATION GOES THROUGH LAPSES AT
MULTIPLE TIMES, DURING THE DELAY
PERIOD, FREQUENTLY FALLS TO
CHANCE LEVELS.
BUT THEN COMES BACK.
AND THESE LAPSES CAN BE LONG OR
SHORT AT ANY GIVEN TRIAL.
HERE IS ANOTHER EXAMPLE OF A
SESSION RECORDED IN MONKEYS.
BOTH EXAMPLES YOU CAN SEE CODING
OF MEMORANDA AND SPIKING
ACTIVITY IS INTERMITTENT.
AND IT'S NOT -- DOESN'T PERSIST.
WHICH IS QUITE CONTRARY TO WHAT,
YOU KNOW, WE LEARNED IN TEXT
BOOKS.
SO IF WE NOW LOOK AT AN
INDIVIDUAL TRIAL, A SLICE, LOOK
AT THE CONFIDENCE AND Y-AXIS
HERE, YOU KNOW, CAN YOU SEE
CLEARLY THAT INFORMATION ABOUT
THE REMEMBERED STIMULUS IS
UNSTABLE DURING THE DELAY
PERIOD.
FURTHERMORE YOU CAN SEE THE
CLASSIFIER FLUCTUATES BETWEEN
DISCRETE PERIODS OF HIGH OF
CONFIDENCE AND PERIODS OF LOW OR
NO CONFIDENCE, SEEMS TO BE WHAT
WE MIGHT CALL ON OR OFF, WE
LABEL AS ON OR OFF BECAUSE IT'S
DISCRETE.
HERE ARE OTHER TRIALS.
THEY CAN ALL LOOK THE SAME,
DISCRETE TRANSITIONS FROM HIGH
CONFIDENCE TO LOW CONFIDENCE.
AS IF MEMORY INFORMATION IS
SWITCHING ON AND OFF.
INDEED IF YOU ANALYZE THE SORT
OF STATS OF THE CONFIDENCE
ACROSS ALL TRIALS AND RECORDING
SESSIONS, WITH GASSING MIXTURE
MODEL OR HIDDEN MARKOFF MIDDLE
DATA FIT A TWO-STATE MODEL AS
OPPOSED TO CONTINUOUS ONE-STATE
MODEL, CONTINUOUS FLUCTUATIONS
BETWEEN LOW AND HIGH CONFIDENCE.
ALL RIGHT.
SO, NOTABLY WE CAN REPEAT
CLASSIFICATION FOR EACH TRIAL
AND TIME POINT IN THE MEMORY
PERIOD.
THIS TIME WE CAN ONLY TRAIN ON
TRIALS WE LABEL AS OFF, AT THE
SAME TIME POINTS AT TEST.
TO CONFIRM OFF IS OFF, ON IS ON.
YOU KNOW, WE CAN SHOW THAT AS
WELL, THIS INDICATES OFF STATES
REFLECT TIME PERIODS WITH
MINIMAL CUE INFORMATION AS
OPPOSED TO LESS FREQUENT, LESS
FREQUENT SECOND CODING SCHEME.
WE HAD LOTS OF OTHER ANALYSES TO
ENSURE THAT THAT WASN'T
HAPPENING, THAT CODING SCHEME
REMAINS THE SAME, JUST THAT
INFORMATION ABOUT THE MEMORANDUM
IS TURNING OFF AND ON.
ALL RIGHT.
NEXT WE ASKED HOW THESE
APPARENTLY DISCRETE FLUCTUATIONS
AND CLASSIFIER CONFIDENCE
MEASURED ACROSS SORT OF
POPULATIONS OF NEURONS REFLECTED
IN ACTIVITY OF INDIVIDUAL
NEURONS, WHAT'S HAPPENING IN
INDIVIDUAL NEURONS.
WE IDENTIFIED ON AND OFF STATES
WITHIN EACH TRIAL USING NULL
DISTRIBUTION OF CONFIDENCE
DERIVED FROM SHUFFLE TRIALS.
SHOWN IN GRAY.
ON STATES WHERE ACTIVITY
CONFIDENCE WAS ABOVE THAT, OFF
WHEN WITHIN THAT.
WE FOUND AVERAGE ON/OFF PERIODS
OCCURRED THREE TIMES A SECOND,
THREE TIMES EACH TRIAL, A BIT
MORE THAN A SECOND.
WE COULD IMPORTANTLY IDENTIFY
THESE STATES USING ONLY HALF THE
NEURONS IN THE POPULATION, AND
THAT ALLOWS US TO ASK THE
QUESTION WHAT'S HAPPENING WITH
THE OTHER NEURONS, IN THE
HELD-OUT POPULATION OF AN
INDIVIDUAL NEURON BASIS.
FOR EXAMPLE WE COULD EXAMINE THE
SPATIAL TUNING FUNCTION OF
REMAINING NEURONS IN LABELED
STATES, LABELED BY THE FIRST
HALF OF NEURONS, AND THEN
MEASURED IN THE SECOND HALF OF
NEURONS.
IT'S KNOWN THAT INDIVIDUAL
LATERAL PSC NEURONS, THE MEAN
NORMALIZED DURING THE LABELED
ONSTATE, WE'RE LOOKING MEAN
NORMALIZED TUNING FOR HELD-OUT
NEURONS, SO THE LABEL IS ON BY
THE FIRST HALF OF NEURONS AS
WE'RE LOOKING AT SPATIAL TUNING
FUNCTIONS, CUE LOCATIONS, THIS
IS THE NORMALIZED ACTIVITY,
DURING OF THE ON PERIOD, THAT'S
DETERMINED BY THE FIRST HALF OF
NEURONS.
OKAY.
SO, REMARKABLY, THE SPATIAL
TUNING, STRONG TUNING DURING
ONPERIOD.
LOOKING DURING THE OFF PERIOD,
IT'S ALMOST GONE COMPLETELY.
THE MEAN NORMALIZED TUNING OF
NEURONS IS PRETTY MUCH
DISAPPEARS.
AGAIN, THOSE LABELS ARE
DETERMINED BY THE FIRST HALF OF
THESE NEURONS.
SO WE ALSO LOOKED AT THE FIRING
RATES OF INDIVIDUAL NEURONS
DURING THE ON AND OFF STATES,
AGAIN IN THE HELD-OUT NEURONAL
POPULATION.
GRAY AVERAGE SHOWS THE AVERAGES
AND ACTIVITY DURING THIS MEMORY
PERIOD, FOR BOTH ON AND OFF, BUT
BLUE SHOWS ACTIVITY DURING THE
OFF AND ORANGE IS FOR THE ON.
SO THAT MEANS THIS SHOWS
NEURONAL FIRING RATES, RETURN TO
BASELINE DURING OFF PERIOD.
LOSS OF TUNING IS DRIVEN BY A
DROP TO BASELINE BY THE NEURONS.
ALL RIGHT.
COMBINED THESE RESULTS SHOW OFF
STATES ARE CHARACTERIZED BY
DRAMATIC LOSS IN MEMORY ACTIVITY
LOSS DRIVEN BY RETURN TO
BASELINE.
IT SHOWS THESE ON AND OFF STATES
ARE COORDINATED ACROSS NEURONS
IN THE LOCAL POPULATION, THAT
MEANS MOMENTARY LAPSES IN
PERSISTENT ACTIVITY FOR SOME
NEURONS IN LOCAL NETWORK ARE NOT
COMPENSATED BY OTHER NEURONS,
THEY ARE ALL SYNCHRONIZED.
WHEN ONE GOES THE OTHER ONES GO
AS WELL.
WE WOULDN'T SEE THIS IF WE
WEREN'T ABLE TO RECORD FROM SUCH
LARGE LOCAL POPULATIONS OF
NEURONS.
ALL RIGHT.
SORRY ABOUT THAT.
OKAY.
YEAH, SO INTERESTINGLY IF YOU GO
BACK AND LOOK AT ACTUAL ANIMAL'S
PERFORMANCE, AT THE END THE
ANIMAL HAS TO RENDER A RESPONSE
INDICATING WHERE THE CUE WAS.
IF YOU LOOK AT THE ANIMAL'S
PERFORMANCE YOU CAN SEE THE
PERFORMANCE IS RELATED TO THE
STATES OF THE POPULATION AT THE
TIME RESPONSE IS REQUESTED SO
THE ANIMAL IS PERFORMING TWO
VERSIONS OF A SPECIAL WORKING
MEMORY TASK, MATCHED SAMPLE TO
INDICATE TWO CUES, TWO STIMULI,
ANIMAL HAS TO INDICATE WHICH
MATCHES THE ORIGINAL OR MAKE A
MEMORY-GUIDED RESPONSE LIKE THE
EXAMPLE I SHOWED EARLIER.
BOTH REQUIRE THE SAME MEMORY,
AND SO BUT YOU CAN SEE FOR THE
BLUE LABELS OFF STATES
PERFORMANCE DROPS AND PRETTY
MUCH IN EVERY CASE, AND THREE
ANIMALS, A TASK WE USED, SORRY,
WE DID THIS EXPERIMENT IN THREE
ANIMALS FOR THIS TASK HERE.
ALL RIGHT.
OKAY.
SO, WE'VE SEEN THESE LARGE
POPULATIONS OF PFC NEURONS
ENCODE MEMORANDA, FAILED TO DO
SO ACROSS THE DELAY PERIOD
CONTRARY TO WHAT WE EXPECTED.
THIS IS IN SPITE OF THE FACT OUR
MONKEYS PERFORM WELL ON SPATIAL
WORKING MEMORY TASK, NO PROBLEM
PERFORMING QUITE WELL AND WE
KNOW DAMAGE OR ACTIVATION TO
LATERAL PSC RESULTS IN CLEAR
DEFICITS TO PERFORM THE TASKS,
SO RECORDING FROM THE PARTS OF
THE CORTEX, PFC TO PERFORM
ADEQUATELY, LEADING US TO ASK IF
NEURONS ARE USING OTHER
MECHANISM OR ADDITIONAL
MECHANISM TO SUPPORT MEMORY
MAINTENANCE.
THAT BRINGS US BACK TO THE
COMPETING NON-SPIKING MODEL OF
WORKING MEMORY, SYNAPTIC MODEL.
AND THIS MODEL AGAIN INFORMATION
HELD IN WORKING MEMORY IS STORED
BY THE PATTERN OF SHORT-TERM
PLASTIC CHANGES INITIATED BY
PARTICULAR MEMORY CUE.
IMPORTANTLY THAT STORED PATTERN
OF STP DOESN'T REQUIRE -- MAY
NOT REQUIRE ELEVATED SPIKING
ACTIVITY, INSTEAD SHOULD ONLY
NEED TO BRING ABOUT CUE-SPECIFIC
CHANGES IN THE ENSEMBLE OF
NEURONS MORE STRONGLY CONNECTED.
SO AS WE SAW IN THE EARLIER PART
OF THE TALK, IN OUR EARLIER
EXPERIMENTS IN MACAQUE V1, ONE
OF THE KEY BENEFITS OF THESE
LARGE SCALE HIGH DENSITY
RECORDINGS IS THAT THEY ALLOW US
TO EXAMINE FUNCTIONAL
CONNECTIVITY AMONG VERY LARGE
MEMBERS OF POPULATIONS, WITH
LARGE NUMBERS EACH RECORDING CAN
YIELD UP TO THOUSANDS OF
RELIABLE FUNCTIONAL CONNECTIONS
BETWEEN NEURONAL PAIRS,
DEPENDING OF COURSE ON THE
LOCATION OF THE RECORDING PROBE.
AND SO HERE ARE TWO EXAMPLES
CROSS-CORRELATIONS MEASURED
BETWEEN PAIRS OF PFC NEURONS IN
MEMORY DELAY PERIOD.
IN ONE NEURONAL PAIR, THERE'S A
RELIABLE CROSS-CORRELATION
DURING DELAY FOLLOWING CUE 1, 5
MILISECONDS, NOT FOLLOWING CUE
2.
HE GET RELIABLE TIME DELAY HERE
AND SECOND PAIR, REVERSE IS
TRUE.
SO CUE 2 YOU GET A
CROSS-CORRELATION, NOT IN CUE 1.
IF CUE-SPECIFIC SHORT-TERM
PLASTICITY TEMPORARILY REO
ORGANIZEs CONNECTED ENSEMBLES
WE MIGHT BE ABLE TO OBSERVE
EVIDENCE IN PATTERN OF PAIRWISE
CROSS-CORRELATIONS OBTAINED, WE
MIGHT EXPECT TO FIND EXAMPLES
LIKE THESE, THIS ONE HERE OCCUR
MORE FREQUENTLY THAN WE EXPECT
BY CHANCE.
THIS PLOT HERE I'M SHOWING THE
FULL SET OF SIGNIFICANT PAIRWISE
CROSS-CORRELATIONS BETWEEN
NEURONS FOR ALL NEURONS RECORDED
IN A SINGLE SESSION SO AGAIN
WE'RE LOOKING AT THAT VIEW OF
NEURONS THAT I SHOWED BEFORE
WHERE THIS IS THE ELECTRODE MAP,
SO THIS IS THE DEPTH OF
ELECTRODE, THIS IS THE WIDTH,
EACH DOT IS A NEURON, EACH EDGE
RECOMMENDS CORRELATION BETWEEN
THE PAIRS ON THE POPULATION IN
THE FACE OF THE PROBE.
AS EXPECTED ONLY A SMALL
FRACTION OF THE POSSIBLE NUMBER
OF CORRELATED PAIRS RELIABLY
CORRELATED USING HIGH STRINGENT
THRESHOLD, BUT YOU CAN SEE
PATTERN OF CONNECTIONS APPEARS
TO DIFFER BETWEEN TWO CUE
CONDITIONS SO THEY DIFFER MORE
THAN WE EXPECT BY CHANCE.
WELL, THIS IS SORT OF WHAT WE'VE
FOUND, THE MEMORY PERIOD, THIS
PLOT SHOWS SET OF CONNECTED
PAIRS FOR TWO LOCATIONS ACROSS
ALL CUES SO FOR -- THIS IS
SHOWING THE -- THIS IS IDENTITY
HERE, CUE 1, CUE 2 TO CUE 2,
DIFFERENT CUE PAIRS SHOWN HERE,
YOU CAN SEE BY EYE FIRST THAT
THE PATTERN DELIVERS BETWEEN TE
TWO CUES DURING THE MEMORY
PERIOD.
WE HAVE TO QUANTIFY THESE
DIFFERENCES AND SEE IF THEY ARE
CONSISTENT ACROSS THE FULL
DATASET.
TO QUANTIFY SIMILARITY BETWEEN
THE SETS OF CONNECTIONS WE
SIMPLY COUNTED NUMBER OF
CONDITION-UNIQUE EDGES,
CONNECTIONS YIELDING MANHATTAN
DISTANCE.
MANHATTAN DISTANCE WAS COMPARED
TO A NULL DISTRIBUTION DERIVED
FROM CONDITION SHUFFLE DATA,
GIVES A Z SCORE.
THIS VIOLIN PLOT SHOWS MANHATTAN
DISTANCE, SIMILARITY IN
CONNECTIONS ACROSS DIFFERENT
CUES FOR ALL THE DATA, ACROSS
THE MEMORY PERIOD.
THE DISTRIBUTION OF DISTANCES IS
RELIABLY DIFFERENT FROM THE
SHUFFLE.
INDEED WE SEE PATTERN OF
FUNCTIONAL CONNECTIONS AMONG
SIMULTANEOUSLY RECORDED NEURONS
DEPENDS ON MEMORY CUE.
IF WE LOOK NOW AT JUST THE ON
STATES, WE KNOW WE HAVE TWO
PERIODS WHERE THE RATE CAN TELL
YOU WHERE THE CUE IS BUT PERIODS
WHERE IT CAN'T, WE LOOK AT THE
PERIOD WHERE IT CAN WE KNOW THAT
INFORMATION BEFORE THE
REMEMBERED CUE IS ROBUSTLY
AVAILABLE IN SPIKING ACTIVITY,
WE SEE PATTERN OF FUNCTIONAL
CONNECTIVITY APPROACHES
DEPENDENCE ON MEMORY CUE BUT NOT
RELIABLE.
WHICH WE WERE QUITE SURPRISED TO
SEE THAT THOSE ON PERIODS DON'T
ACTUALLY GIVE YOU YIELDING
RELIABLE DIFFERENCE IN ENSEMBLE
CONNECTIVITY ACROSS THE CUES.
DURING THE OFF STATES, YOU KNOW,
THE PATTERN OF FUNCTIONAL
CONNECTIVITY BETWEEN NEURONS
REALLY RELIABLY DEPENDS ON
MEMORY CUE.
INDEED OVERALL DIFFERENT IN CUE
DEPENDENT ENSEMBLES SEEMS TO BE
DRIVEN BY OFF STATES, THE
CONNECTIVITY IS IN CONTRAST
DURING THE ON PERIODS.
THIS INDICATES DURING PERIODS IN
WHICH SPIKING ACTIVITY FAILED TO
SIGNAL WHICH CUE WAS BEING
REMEMBERED, THAT INFORMATION IS
NONETHELESS AVAILABLE IN UNIQUE
SET OF NEURONAL ENSEMBLES
ASSOCIATED WITH MEMORY CUE
SUGGESTING THEY SPAN THE
INTERMITTENT RATE CODING OF
REMEMBERED STIMULI.
THAT'S DURING THE MEMORY PERIOD
WHEN FIRING RATE CODING OF
MEMORANDA LAPSES, CUE-SPECIFIC
PATTERNS, YOU KNOW, PATTERN OF
CONNECTIONS MORE RELIABLE
CONNECTIONS REMAINED.
AND SO SUBSEQUENTLY CUE-SPECIFIC
ELEVATION IN FIRING RATE MAY
REEMERGE DUE TO NON-SPECIFIC
FLUCTUATIONS, ACROSS MEMORY
DELAY PERIOD MULTIPLE
TRANSITIONS BETWEEN SPIKING
ACTIVITY AND ACTIVITY SILENT ON
AND OFF MAY OCCUR, THIS WOULD BE
SIMILAR TO WHAT IS PREDICTED IN
SYNAPTIC MEMORY, AND INTERPLAY
WHEN THE SILENT AND SPIKING
MECHANISMS.
ALL RIGHT.
AND ONE LAST PIECE OF -- THAT
WOULD MEAN THERE SHOULD BE A
RELATIONSHIP BETWEEN THE MAPPING
OF THE ENSEMBLE OF NEURONS THAT
ARE CO-ACTIVATED DURING EACH CUE
AND ENSEMBLES THAT ARE
ASSOCIATED DURING THE OFF
PERIODS.
SO WE'RE LOOKING AT HERE SHOWING
THE PROBABILITY OF TWO NEURONS
ON AVERAGE HAVING A PREFERENCE
FOR THE SAME CUE, ONE OF EIGHT
CUES.
THIS IS SHOWING ACROSS ALL THE
DATA SHOWING PROBABILITY OF TWO
NEURONS SHOWING RELIABLE
CROSS-CORRELATION HERE, OKAY,
AND SO NOW IF THESE TWO ARE
INDEPENDENT THEN IF YOU LOOK AT
THE -- COMPARE THE JOINT
PROBABILITY OF NEURONS
PREFERRING THE SAME CUE AND ALSO
BEING CONNECTED, THAT SHOULD BE
AT UNITY WITH THE PRODUCT OF THE
TWO THINGS BUT ACTUALLY IT
EXCEEDS THAT, MEANING THERE'S A
RELATIONSHIP BETWEEN ENSEMBLES
DURING THE CUE AND DURING THE
OFF PERIODS.
OKAY.
SO, YOU KNOW, RESULTS PROVIDE
THE BEST EVIDENCE TO DATE
INTERPLAY BETWEEN SPIKING
MECHANISM AND ACTIVITIES, THESE,
SORRY, WHERE DID I GO?
OH, DIDN'T KNOW THAT WAS THERE.
OKAY, RIGHT.
PREFRONTAL CORE NEXT MNEMONIC
INFORMATION DOES NOT PERSIST,
BUT IF YOU LOOK AT THE ACTUAL
INFORMATION CONVEYED BY
POPULATIONS OF NEURONS LOCALLY,
THAT ACTIVITY, THOSE SIGNALS DO
NOT PERSIST BUT ALTERNATE
BETWEEN DISCRETE AND COORDINATED
PERIODS OF ON AND OFF STATES.
AND AT THE LEVEL OF SINGLE
NEURONS OFF STATES ARE DRIVEN BY
LOSS OF SELECTIVITY FOR
MEMORANDA AND RETURN OF FIRING
RATES TO BASELINE LEVELS, AGAIN
COORDINATED FASHION.
DURING OFF STATES MNEMONIC
INFORMATION IS AVAILABLE,
PATTERN OF FUNCTIONAL
CONNECTIONS.
OBSERVATIONS ARE ENABLED, MADE
POSSIBLE BY THIS NEWLY ACQUIRED
ABILITY TO ACHIEVE LARGE-SCALE
HIGH-DENSITY RECORDINGS WITH
NEURONAL PIXELS.
LET ME STOP AND THANK MY
COLLABORATORS, MY STUDENT, MATT,
AND DONATAS HERE.
BARUN FROM IMEC AND TIM HARRIS
FOR DEVELOPING NON-HUMAN PRIMATE
PIXEL PROBES AND OF COURSE MY
FUNDERS INCLUDING THE BRAIN
INITIATIVE.
ALL RIGHT.
I'LL STOP THERE.
>> WOW, AMAZING.
s LET'S SEE IF WE HAVE TIME
FOR QUESTIONS.
IF YOU CAN STOP SHARE AND TURN
YOUR CAMERA ON, THAT WOULD BE
GREAT.
>> WHERE IS THAT?
SORRY, I'M DOING THIS NOT FROM
MY NORMAL LOCATION, I'M ACTUALLY
IN THE U.K. RIGHT NOW.
>> WE APPRECIATE YOUR ZOOMING IN
FROM ACROSS THE POND.
>> I CAN'T FIND THE SHARE
BUTTON.
OH.
>> EVERYBODY IS WELCOME TO TURN
CAMERAS ON.
I SEE SAMEER, YOU HAVE A
QUESTION.
>> YEAH.
>> WE SEE YOU, TIRIN.
>> THAT WAS FANTASTIC.
REALLY ENJOYED THAT.
A BUNCH OF QUESTIONS.
I'LL KEEP IT TO ONE.
JUST PRACTICAL ONE.
I MEAN, WE'VE HAD A LOT OF
EXPERIENCE WITH THESE PROBES,
ONE OF THE FEW TO HAVE
EXPERIENCE WITH THE NEW VERSION,
DESIGNED FOR NHP.
CAN YOU SAY ANYTHING, TELL US
ABOUT WHAT YOU THINK THE
PROSPECTS ARE FOR, YOU KNOW,
LARGER SCALE USE OF THESE
THINGS.
HOW EASY OR HARD ARE THEY TO
HANDLE RELATIVE TO PREVIOUS
ONES, IN TERMS OF BRITTLENESS,
DRIFT, IN TERMS OFS RECORDING
CAPABILITY AND CHARACTERISTICS,
AND THEN DO YOU THINK -- WHAT'S
THE TIMELINE FOR HUMAN USE DO
YOU THINK?
>> WELL, IF YOU'RE ASKING IMEC
THEY WOULD SAY THEY ARE NOT
INTENDED FOR HUMAN USE AS YOU
PROBABLY NOW.
YOU'RE ON YOUR OWN. THERE A
COUPLE THINGS TO UNPACK.
HANDLING IS A COMMON
MISPERCEPTION.
I'LL SUMMARIZE WHAT HAPPENS WHEN
FOLKS ARE USING THE PRIMATE
PROBE, WE'LL CALL THEM THAT.
YOU BREAK ONE OR TWO, AND YOU
STOP BREAKING THEM FOR YEARS.
AND SO IF YOU ASKED -- FOUR
PEOPLE IN MY LAB HAVE BEEN USING
THEM FOR YEARS, MAY HAVE BROKEN
ONE OR TWO, LIKE TWO YEARS AGO,
AND THEY STOPPED BREAKING THEM.
YEAH, THEY ARE MORE FLEXIBLE
THANK YOU THINK.
PRIMARY PROBES ARE 120 MICRONS
WIDE, DEEP, THEY ARE PRETTY
RESILIENT.
SO THAT'S THAT.
WE DIDN'T GO THROUGH AS MANY AS
WE THOUGHT WE WOULD GO THROUGH
OVER THE YEARS.
A LOT MORE ROBUST THAN FOLKS
THINK THEY ARE.
DRIFT, YEAH, IT'S A NON-TRIVIAL
PROBLEM.
NOW, AMONG THE KIND OF NON-HUMAN
PRIMATE MONKEY EFIZ PEOPLE
THERE'S A BROAD DISTRIBUTION
WITH RESPECT TO HOW LONG YOU
WAIT AFTER YOU INSERT THE PROBE,
JOHN CAN CONFIRM THAT.
SOME WAIT, START RECORDING RIGHT
AWAY, SOME WAIT THREE HOURS FOR
THE BRAIN TO SETTLE DOWN AND
RELAX.
YOU STILL GET DRIFT.
THAT'S PART OF THE SPIKE,
CLUSTERING PROCEDURES, YOU CAN
LOOK AT THE DRIFT OVER TIME.
USUALLY WITHIN AN HOUR OR SO THE
DRIFT REDUCES QUITE A BIT,
THAT'S IN THE METHODS PAPER
COMING OUT.
THAT WAS QUITE A BIG THING.
AND SO THAT'S NOT A HUGE
PROBLEM.
OBVIOUSLY IF WE WERE RECORDING
IN HUMANS, YOU HAVE A LIMITED
WINDOW OF TIME TO RECORD, THAT'S
A SERIOUS PROBLEM AND ONE THAT
HASN'T BEEN SOLVED YET.
YEAH, WHAT WAS THE LAST
QUESTION, ABOUT THE HUMAN?
YEAH, THE NEXT GENERATION, 3.0,
WHICH IS NOW OFFICIALLY STARTING
LIKE IN A FEW DAYS, WHICH 3.0
ALLOWS FOR FOUR TIMES THE NUMBER
OF ACTIVE CHANNELS SO 4400
CHANNELS NOW, IT WILL BE --
LENGTH WILL BE EXTENDED TO 60
MILLIMETERS BUT EFFECTIVELY 50
MILLIMETERS OF CONTACTS SO ^5
THOUSAND CONTACTS, 1536 CAN BE
RECORDED ACTIVELY, THAT
INCREASES THE YIELD.
AND THE FRACTION OF THE ENTIRE
LENGTH OF THE PROBE THAT YOU CAN
RECORD.
A COUPLE THINGS WILL BE
DIFFERENT BUT THOSE, YOU KNOW,
NOTHING KEEPING FOLKS FROM USING
THOSE IN HUMANS TOO.
IN FACT A LOT OF THE FUTURE
HUMAN-SPECIFIC PROJECTS ARE
GOING TO BE BENEFITING FROM THIS
NEW NHP DESIGN.
MUCH LIKE THE NHP DESIGNS ARE
BENEFITING FROM NEW VERSIONS OF
THE PROBES, THERE'S A LOT COMING
DOWN THE PIKE, AT LEAST TWO NEW
PROJECTS THAT WILL AFFECT HOPES
FOR USE IN HUMANS.
>> THANKS, TIRIN.
>> FRANK AND JOHN.
>> HI, TIRIN.
YOU HAD THE GREAT TALK, THE ONE
SLIDE THAT SHOWED DIFFERENT
PATTERNS, AND IT MADE ME THINK
OF ISSUES OF PLASTICITY AND THEN
DIFFERENT STATES THAT MIGHT
CHANGE WITH AGING.
WOULD YOU EXPECT THE RANGE OR
DIVERSITY OF PATTERNS TO BE
REDUCED IN PATHOLOGIC STATES OR
WITH AGING OR INCREASE IN
LEARNING PARADIGM?
I'M INTERESTED IN DIVERSITY OF
PATTERNS THAT YOU SAW.
>> YEAH, I MEAN, YOU KNOW, AN
EXPERT ON, YOU KNOW, PATTERNS OF
CROSS-CORRELATION AMONG, YOU
KNOW, LARGE NEURONAL POPULATIONS
BECAUSE THE FIRST TIME YOU COULD
EVER LOOK, YOU KNOW, TO SEE IT,
RIGHT?
MOST OF THE CROSS-CORRELATION
STUDIES OVER THE PAST SEVERAL
DECADES ARE VERY LOW YIELD AND,
YOU KNOW, THERE ARE VERY FEW,
WELL, THAT I WOULD TEND TO KNOW
ABOUT.
I MOSTLY KNOW ABOUT ITS USE IN
THE VISUAL SYSTEM, THERE AREN'T
MANY PLASTICITY STUDIES.
YOU CAN ASK QUESTIONS, YEAH,
JUST HOW MUCH VARIABILITY,
ENSEMBLES, WHICH EVER APPROACH
YOU USE, LOOKS LIKE DEVELOPMENT
OVER AGING, PATHOLOGY, SO FORTH,
WHY NOT?
>> YEAH, ASSUMING VARIABILITY IS
A GOOD THING, I DON'T KNOW, THAT
WOULD BE MY HYPOTHESIS AT LEAST
AND HOW DOES THAT CHANGE?
>> YEAH, YEAH.
>> OR MAYBE WITH LEARNING IT
GETS REDUCED, I DON'T KNOW.
BUT SEEMS LIKE WHAT YOU'VE DONE
OPENS A DOOR TO A LOT OF
QUESTIONS ONE COULD ADDRESS WITH
THAT MAYBE.
>> YEAH, IT'S EMBARRASSINGLY
EASY, IT'S SUCH A TORRENT OF
DATA.
AND, YOU KNOW, WHEN WE FIRST
STARTED USING THESE PROBES ONE
OF THE QUESTIONS WE WERE ASKING
OURSELVES, WELL, WHAT'S
QUALITATIVELY DIFFERENT?
MORE NEURONS?
YOU DO EXPERIMENT IN SHORTER
AMOUNT OF TIME?
OR IS THERE SOMETHING WE
COULDN'T DO BEFORE?
THIS IS ONE OF THOSE THINGS.
>> RIGHT.
>> THEN YOU GET SO MUCH POWER
FROM A SINGLE RECORDING AND
LOOKING AT NEURONS THAT ARE,
LIKE I SAID, LARGE LOCAL
POPULATIONS WITH PROBABILITY OF
CONNECTIVITY OF SOME TYPE THAT'S
MUCH HIGHER.
THE DATA I SHOWED YOU, AVERAGE
RATE OF CONNECTIVITY, A STRANGE
CRITERION FOR CROSS-CORRELATION,
LIKE SEVEN SIGMA.
>> WOW.
>> LIKE 1 1/2% OF THE NEURONS
ARE CONNECTED.
ONE 1 1/2 IS PLENTY WHEN YOU'VE
GOT WHATEVER, YOU KNOW, WHATEVER
THE NUMBER OF POSSIBLE PAIRS SO
HIGH.
>> WELL, THANK YOU.
>> IF I COULD JUMP IN WITH A
FOLLOW-UP QUESTION, SO DO YOU
SEE A POINT OF DIMINISHING
RETURNS?
IN OTHER WORDS WE'RE STILL AT A
POINT WHERE GETTING MORE CELLS
INVOLVED, MORE DENSE RECORDINGS,
IS TELLING YOU THINGS YOU
WOULDN'T SEE BEFORE BUT FOR
EXAMPLE HAVE YOU TRIED
SUBSAMPLING YOUR DATA TO SEE HOW
DID YOUR CLASSIFIER WORK AS YOU
KIND OF MAKE THE DATA MORE
SPARSE?
THE CONNECTIONS DO SEEM TO BE
SPARSE TO SOME DEGREE AS WELL.
>> YEAH, SO -- WE DID ONE THING
LIKE SUBSAMPLING, TOOK HALF
NEURONS TO CLASSIFY, CATEGORIZE
THE STATE, RIGHT?
WE LOOKED AT THE HELD-OUT, A
SUBSAMPLING.
LET ME SEE WHAT YOU'RE SAYING.
YEAH, GIVE ME SOMETHING
CONCRETE, WHAT WOULD WE --
>> I MEAN, DO YOU THINK YOU
WOULD LEARN MORE IF YOU
INCREASED DENSITY RECORDINGSED
BY 4X OR REDUCED BY HALF?
>> OH, DENSITY?
I MEAN --
>> OR BOTH.
>> REALLY GOOD POINT.
I GUESS, YEAH, THAT'S AN
EMPIRICAL QUESTION.
THIS IS RELEVANT TO THE LAYOUT
OF THESE CONTACTS BECAUSE YOU
MIGHT HAVE NOTICED THAT OR YOU
MIGHT KNOW OR NOTICED, WHATEVER,
THAT BECAUSE THE NHP PROBE IS
WIDER, THE ARE THERE ARE TWO
COLUMNS OF CONTACTS SEPARATED,
AND SO THE DISTRIBUTIONS OF
NEURONS YOU PICK UP ARE
SEPARATED INTO TWO COLUMNS SO
DENSITY IS DIFFERENT THAN IT IS
IN THE RODENT WHERE THEY ARE
CLUMPED TOGETHER, DOES THAT
AFFECT THE YIELD OR OTHER THINGS
YOU MIGHT WANT TO ASK?
YEAH, THAT'S A GOOD QUESTION.
I ALLUDED TO IT IN ONE SLIDE,
MULTIPLE LONG RECORDING IN
VISUAL SYSTEM, NON-SIMULTANEOUS,
I'M SORRY, THAT MAY BE RELEVANT,
BUT THIS IS ALL JUST WITH A
SINGLE PROBE, RIGHT?
I MEAN, THE IDEA OF ADAPTING
RODENT PROBES FOR MONKEYS
ACTUALLY WAS ORIGINALLY SPURRED
BY NICK STEINMETZ WHO BASICALLY
WORKED IN MY LAB AND WORKED WITH
RODENTS AND SORT OF REALIZED,
WELL, IN THE MONKEY BRAIN YOU
COULD DEPLOY TEN, TWELVE OF
THESE IN A SINGLE ANIMAL, SO
WE'RE STARTING TO DO THAT NOW.
THAT'S WHERE THE REAL -- IT'S
GOING TO GET REALLY, REALLY
INTERESTING BECAUSE NOW YOU CAN
LOOK AT NEURONS CONNECTED
ACROSS, YOU KNOW, DISTRIBUTED
CONNECTIONS ACROSS THE BRAIN OR
VISUAL SYSTEM, WHATEVER, IN
LARGE NUMBERS, LARGE LOCAL
POPULATIONS BUT ALSO DISTAL
NETWORKS, YEAH.
>> THANKS.
SORRY, JOHN.
JOHN AND TOR.
>> AMAZING DATA.
REALLY FASCINATED BY SEEING THIS
VIEW ON SO MANY CELLS
SIMULTANEOUSLY.
AND IN PARTICULAR IT'S GREAT
THAT YOU CAN PULL OUT THESE
THINGS, ON AND OFF TRIALS, BUT I
GUESS MY SUBSAMPLING QUESTION
WOULD BE IT'S NOT THAT
SURPRISING, DIFFERENT THINGS
WHEN THE ANIMAL IS PERFORMING
BETTER OR PERFORMING WORSE,
WONDERING WITH THE DENSITY OF
DATA THAT YOU HAVE HERE WHETHER
YOU MIGHT SUBSAMPLE ON AND OFF
TRIALS TO GET TRIALS THAT WERE
EQUIVALENT IN TERMS OF BEING
CORRECT, SAME REACTION TIME.
>> YEAH.
>> ACCURACY AND SO YOU CAN
ACTUALLY COMPARE THOSE TWO
STATES DIRECTLY.
>> YEAH, YEAH, I PROBABLY --
MAYBE THE AUDIO WASN'T WORKING
WELL BUT I DID SHOW A SLIDE
WHERE IF YOU LOOKED AT WHATEVER
STATE THE POPULATION WAS IN AT
THE END OF THE TRIAL, AND LOOKED
AT THE PROPORTION OF CORRECT OR
WRONG, SO CORRECT WAS HIGHER FOR
ON THAN OFF IN ALL THREE
ANIMALS, WHETHER IT WAS MATCHED
SAMPLE TASK OR MEMORY GUIDED
TASK, AND REACTION TIMES WERE
SHORTER IF THE END OF THE TRIAL
CAME DURING AN ON PERIOD VERSUS
OFF PERIOD.
>> WHAT I'M ASKING IS CAN YOU
CORRECT FOR THAT BY SUBSAMPLING
SO YOU HAVE EQUIVALENT TRIALS IN
THE OFF STATE AND ON STATE?
>> EQUIVALENT?
>> ONLY CORRECT TRIALS, SAY.
>> TAKE THE ONLY CORRECT TRIALS?
IF WE TAKE ONLY THE CORRECT
TRIALS, I ASSUME WE WOULD FIND
PROBABILITY OF BEING IN ON STATE
AT THE END OF THE TRIAL IS GOING
TO BE HIGHER THAN OFF STATE.
THAT'S JUST THE COMPLEMENT OF
WHAT I SAID BEFORE.
>> MAYBE WE CAN TAKE THIS UP
OFFLINE.
>> SUBSAMPLE, THE STATES ARE
COORDINATED, RIGHT?
EPIC OF ON OR OFF IS DIFFERENT
FOR SUBPOPULATIONS, IT'S THE
SAME FOR THE OTHER POPULATION,
RIGHT?
THAT WAS THE HELD-OUT ANALYSIS,
RIGHT?
>> UH-HUH.
>> MAYBE I'M MISSING SOMETHING.
>> I'M TALKING ABOUT BALANCING
FOR THE BEHAVIOR SO WE HAVE
EQUIVALENT BEHAVIORS FOR THE
TRIALS THAT ARE BEING COMPARED.
>> YEAH, YOU COULD SAY WHAT
HAPPENS TO THE PERFORMANCE IF
YOU EQUATE, DO SUBSAMPLE TRIALS
PROPORTION OF TIME ON OR OFF WAS
DIFFERENT OR EQUAL, YOU COULD DO
THAT TOO, RIGHT?
BECAUSE, YOU KNOW, IT'S NOT
CLEAR, YOU KNOW, IT'S NOT --
IT'S NOT REALLY CLEAR IT SHOULD
BE THE CASE THAT PERFORMANCE IS
GOING TO BE AFFECTED BY THE OFF
STATE BECAUSE IN THE MODEL FROM
-- I FORGET HIS NAME,
SILENT PERIOD IS STILL THERE, SO
IT DOESN'T HAVE TO FOLLOW THAT
THE OFF PERIOD IS A PERIOD IN
WHICH PERFORMANCE WILL BE BAD,
RIGHT?
BECAUSE THE INFORMATION IS STILL
THERE, JUST THERE -- JUST NOT
THERE IN THE FIRING RATE.
SO WE'RE ALREADY ASSUMING THAT,
YEAH, SO IN THE MODEL YOU WOULD
THINK THOUGH THAT THE
PERSISTENCE OF MEMORY REALLY HAS
TO DO WITH INTERPLAY BETWEEN THE
DIFFERENT STATES, YOU KNOW,
ACTIVITY COMES IN, THERE'S SOME
EITHER EXTRINSIC OR INTRINSIC
FIRING RATE, THAT MAY
ACTUALLY -- THE STRENGTH MAY
ACTUALLY, YOU KNOW, INFLUENCE
THE STRENGTH OF THE ENSEMBLE,
RIGHT?
WHAT YOU WANT TO KNOW, TO LOOK
AT BEHAVIOR, WHEN THAT DOESN'T
WORK SO WELL.
RIGHT?
OR MAYBE THE PEAKS AND
CONFIDENCE, MEASURING BY
CONFIDENCE DURING ON PERIODS AND
RELIABILITY OF THESE ENSEMBLES
ARE NOT GREAT, THAT AFFECTS
PERFORMANCE, THAT SHOULD BE A
BETTER PREDICTOR OF PER FORMANCE
PERHAPS.
THE OTHER THING HIDDEN IN THE
BACKGROUND HERE, WHAT IS IT
WE'RE PICKING UP WITH
CROSS-CORRELATIONS, WITH
ENSEMBLES, RIGHT?
YOU'RE PICKING UP BASICALLY
THESE ARE DRIVEN BY DIFFERENCES
IN RELATIONSHIP AND ACTIVITY
BETWEEN ONE NEURON AND ANOTHER
WHEN THEY ARE NOT FIRING ABOVE
BASELINE, RIGHT?
PATTERN SIGNAL IS GOING ON THAT
MIGHT BE ENCODING THE MEMORANDUM
EVEN IF THE AVERAGE FIRING RATE
IS THE SAME.
WE'RE LOOKING AT USING THE
TEMPORAL PATTERNS OF ACTIVITY IN
SHORT TIME SCALES, YOU KNOW,
TENS OF MILLISECONDS BECAUSE
THAT WOULD BE THE NATURAL
CONSEQUENCE OR COROLLARY OF
THESE DIFFERENCES IN
CROSS-CORRELATION BECAUSE THOSE
ARE RELIABLE PATTERNS OF
ACTIVITY BETWEEN PAIRS OF
NEURONS, THAT SUGGESTS THERE'S A
TEMPORAL PATTERN OF SPIKING
ACTIVITY THAT'S ENCODING THE
MEMORANDUM, RIGHT?
IF IT ISN'T A MECHANISM, IF WE
APPLY A DECODER THAT WAS
SENSITIVE TO TEMPORAL PATTERNS
NOT JUST THE FIRING RATE, RIGHT,
SHORT TIME SCALES, LIKE 20
MILLISECONDS OR SO WE MIGHT BE
ABLE TO FIND THAT THERE'S
PERSISTENT -- STEADY THROUGHOUT
THE DELAY PERIOD.
DOES THAT MAKE SENSE?
YEAH, YEAH.
WE'RE KIND OF DOING THAT NOW.
THERE'S SOME EVIDENCE SO FAR BUT
IT'S HARDER THAN WE THOUGHT.
>> GREAT.
TOR?
>> HI, THAT'S SUPER COOL WORK.
I'M WONDERING IF YOU THINK THE
ON AND OFF STATES MIGHT BE
RELATED TO REHEARSAL IN WORKING
MEMORY, IF THAT MIGHT BE
CONNECTED, MAINTAINING THE
PATTERNS EVEN IN OFF STATES IN
OTHER REMOTE REGIONS?
>> HMM, YEAH, GREAT QUESTION.
I'M TRYING TO FIGURE OUT WHAT
WOULD WE DO TO EXPLORE THAT.
HOW WOULD WE -- THAT'S A GREAT
QUESTION THOUGH.
WHAT WOULD WE DO?
>> YEAH, SO I GUESS AT THE
NEURAL LEVEL IF THEY ARE
CORRECTED FRONT PARIETAL AREAS,
REVERBERATION BETWEEN THE
CIRCUITS, IF YOU COULD FIND
AREAS WITH COMPLEMENTARY
REPRESENTATIONS.
>> YEAH, YEAH, DEFINITELY ONE OF
THE NEXT STEPS IS RECORD OTHER
PLACES WHERE, HAVE PERSISTENT
ACTIVITY TO SEE IF IT HAS
SIMILAR PROPERTIES.
REGARDING REHEARSAL, HOW WOULD
WE KNOW THAT THESE STATES, YOU
KNOW, ARE RELATED TO REHEARSAL,
LIKE WHAT'S THE BEHAVIORAL
MEASURE THAT THIS IS AHA, YOU
KNOW.
>> YEAH, WELL, I STUDY HUMANS,
YOU JUST ASK THEM.
MAYBE IN A MONKEY, MOVEMENTS,
WHAT'S THE NATURAL, YOU KNOW,
TIME LAG TO MAKE AN EYE MOVEMENT
TO REFRESH ESSENTIALLY THE
ACTIVITY AT THE ATTENDANT
LOCATION, EVEN IF YOU'RE NOT
LETTING THEM MOVE THEIR EYES IN
THE TARGET TASK PRESUMABLY.
YEAH, MAYBE THERE'S SOME
TEMPORAL LATENCY OR
DISTRIBUTION, YOU KNOW, WHERE
THEY MOVE THEIR EYES.
AND THAT WOULD BE A CUE TO SORT
OF -- REHEARSAL CUE, THAT'S
REFRESHING THE REPRESENTATION.
>> ONE THING, YOU KNOW, THERE'S
SOME EVIDENCE THAT REHEARSAL AND
SPATIAL WORKING MEMORY IS
RELATED TO (INDISCERNIBLE), AM I
RIGHT ABOUT THAT?
MAYBE FROM HUMAN DATA OR MONKEY
DATA.
WE DID LOOK AND DIDN'T FIND --
GOING IN I THOUGHT THAT'S A
POSSIBILITY BUT WE ACTUALLY
WERE -- DIDN'T FIND MUCH
EVIDENCE FOR THERE BEING
DIFFERENCES, IN YOU WILL, IN THE
PATTERN, DISTRIBUTION OF
PROBABILITY OF MICRO SECAS IN ON
[OFF MICROPHONE] STATES, MAYBE
THERE ARE OTHER MEASURES WE
COULD EXPLORE, A GREAT QUESTION.
>> DATA FROM V1 TOOK ME BACK 60
YEARS, WITH THIS KIND OF
RECORDING WHAT CAN WE LEARN THAT
WE MIGHT NOT HAVE KNOWN OR HAVE
EVIDENCE FOR AT THE POPULATION
LEVEL FOR COMPLEX CELLS, WHAT
ARE STATISTICS.
>> GREAT QUESTION.
THE ONLY -- WELL, THE RESULT
THAT'S PROBABLY THE MOST SALIENT
THAT WE CAME ACROSS, IT'S KNOWN
BY NOW BUT SO EASY TO SEE IT,
EARLY ON THERE WAS DEBATE, IN
THE MONKEY, THE ASSERTION
THERE'S NO ORIENTATION
SELECTIVITY IN LAYER 4, 4C,
RIGHT?
OR IT WAS -- AND THEN MAYBE 4C
BETA, MAYBE JOHN REMEMBERS WHICH
ONES.
BUT THAT WAS THE ASSERTION, LIKE
IT'S ALL --
>> IN THE TEXT BOOKS, SURE.
>> EXACTLY.
BUT WE HAVE HUGE SUBPOPULATIONS,
4C ALPHA AND BETA, IF YOU LOOK
AT THE READOUT IT'S EVEN BETTER
IN LAYER 4 THAN FIVE-SIX, AND
TWO-THREE, AND YOU CAN SEE THAT
IN A SINGLE SESSION.
YOU GET SO MANY NEURONS IN THE
COMPARTMENTS YOU CAN COMPARE
DIRECTLY.
THAT'S PARTLY THE RESULT OF
LOW -- JUST THE LARGER SPIKING
RELIABILITY OF NEURONS IN 4 C
ALPHA AND 4C BETA.
YEAH, INFORMATION ABOUT
ORIENTATION, AND I THINK EVEN
THE THRESHOLD OF ORIENTATION,
BUT ANYWAY, IT WAS A SLAM DUNK,
CLEARLY ORIENTATION INFORMATION
IS THERE BECAUSE YOU CAN COMPARE
NEURONS WITHIN THE SAME COLUMN,
RIGHT?
IF YOU'RE DOING AN EXPERIMENT,
APPLES TO APPLES COMPARISON
BECOMES DIFFICULT, RIGHT?
AND GETTING SUFFICIENT NUMBERS
OF NEURONS IN THE SAME COLUMN,
SAME PART OF VISUAL SPACE, ET
CETERA, ET CETERA.
>> RIGHT.
AS YOU GO TO THE PROPERTIES,
COMPLEX CELLS, HOPEFULLY YOU
COULD GET IDEA ABOUT WHAT THE
ACTUAL INPUTS ARE AND HOW THEY
ARE WEIGHTED.
OR NOT.
>> ANOTHER THING THAT POPS OUT
THAT WAS NICE IF YOU GOT
PUTATIVE FEED,
CROSS-CORRELATIONS, YOU KNOW,
THEY SHOULD TEND TO BE SIMPLE TO
COMPLEX, THAT WAS VERY
ENCOURAGING.
>> ANY OTHER QUESTIONS FROM THE
GROUP?
THANK YOU, TIRIN.
REALLY FASCINATING.
A WHOLE NEW WORLD OUT THERE
WAITING FOR US TO DISCOVER.
OKAY.
ANY LAST WORDS BEFORE WE WRAP UP
OPEN SESSION?
WHEN I WAS SAYING FAREWELL TO
KAV AND BRUCE I HAD SLIDES UP
AND DIDN'T HAVE A CHANCE TO ASK,
BRUCE, I DON'T KNOW IF KAV IS
HERE, IF YOU WANT TO SAY A FEW
WORDS.
I'LL PUT YOU ON THE SPOT, BRUCE.
>> JUST THAT IT'S BEEN AN
AMAZING RUN.
I TOLD YOU, JOHN, I CERTAINLY
LEARNED A HELL OF A LOT MORE
THAN I'VE MANAGED TO TEACH OVER
THE YEARS.
IT'S BEEN PRETTY COOL TO THINK
ABOUT BRAIN, YOU KNOW, FROM THE
BEGINNING.
AND I WAS THINKING ABOUT KIND OF
THE PARALLELS OF THE BRAIN
INITIATIVE TO THE BRAIN ITSELF,
YOU KNOW, HOW COMPLEX BEHAVIORAL
GOAL, YOU KNOW, GOT ENABLED BY,
YOU KNOW, A DIRECTED AND
COORDINATED SERIES OF INDIVIDUAL
EVENTS.
YOU KNOW, VISION LAID OUT BY
CORY AND BILL, YOU KNOW, 2025
REPORT, YOU KNOW, A DECADE AGO
REALLY REMARKABLY SET THE TREND,
YOU KNOW, WALTER AND JOSH KIND
OF LEADING IT AND ALL THE
PROGRAM OFFICERS KIND OF
CREATING FROM SCRATCH, YOU KNOW,
A PROGRAM.
YOU COMING IN TO LEAD IT.
YOU KNOW, SET THIS VISION.
BUT IN THE END THE INDIVIDUAL
WORK WE'VE JUST SEEN, THE PAPERS
YOU POINTED OUT SHOW THAT YOU
CAN REALLY DO BIG SCIENCE BUT DO
IT, YOU KNOW, ELEMENT BY ELEMENT
AND, YOU KNOW, THE COHERENCE
EMERGES.
IT DOESN'T HAVE TO BE
ARTICULATED FROM THE START.
SO IT'S BEEN GREAT TO WATCH
REALLY.
YEAH, IT'S AMAZING WHAT YOU GUYS
HAVE ALL CREATED, CERTAINLY
LOOKING FORWARD TO SEEING WHAT
YOU ALL ACCOMPLISH IN THE NEXT
DECADE AND HOPE TO BE A SMALL
PART OF IT.
>> APPRECIATE ALL YOU'VE DONE
FOR BRAIN AND ME PERSONALLY.
YOU WERE SUCH A GENEROUS SOURCE
OF INFORMATION AND INSIGHT.
WE KNOW WHERE TO FIND YOU.
WE'RE NOT GOING TO LET YOU GO
THAT EASY.
KAV IS HERE.
ARE YOU AT THE AIRPORT OR
SOMETHING?
IT'S BEEN GREAT HAVING YOU HERE.
I REMEMBER, A PERSONAL STORY,
WHEN I CAME ON, I HAD THE
OPPORTUNITY TO BRING ON
ADDITIONAL AT-LARGE MEMBERS,
FOLKS THAT DON'T REPRESENT ICs
DIRECTLY AND I FOUND KAV, PEOPLE
SAID YOU HAVE TO TALK TO KAV.
WE HAD A GREAT CONVERSATION,
MAYBE 45 MINUTES, AN HOUR.
BY THE END I WASN'T SURE WHO WAS
INTERVIEWING WHOM BUT IT ALL
WORKED OUT.
LOVE TO HEAR A FEW WORDS.
YOU'VE BEEN A GREAT SOURCE OF
COUNSEL, GUIDANCE, PERSPECTIVES.
WE APPRECIATE ALL THAT YOU DO
NOT JUST IN YOUR SCIENCE,
ADVOCACY, ALL YOU CONTRIBUTED TO
BRAIN, I WANT TO GIVE AN
OPPORTUNITY TO SAY HI AND
FAREWELL TO EVERYBODY HERE.
>> YEAH, IT'S BEEN A FANTASTIC
HONOR AND PLEASURE TO BE HERE.
I'VE BEEN EXCITED SINCE
INCEPTION OF BRAIN WATCHING IT
GROW, AND THE OPPORTUNITY TO
SHARE MY THOUGHTS AND INSIGHTS,
AND HOW THE INITIATIVE GREW.
FOR ME THE PROBLEM IS THE BRAIN
IS UNDERSTANDING THE HUMAN BRAIN
SO WE CAN ULTIMATELY TRANSLATE
TO IMPROVING HUMAN HEALTH, IT'S
BEEN GREAT TO SEE TRAJECTORY THE
INITIATIVE HAS GONE IN THAT
DIRECTION.
SORRY FOR THE PERSON TALKING IN
THE BACKGROUND.
I AM AT THE AIRPORT.
AND I'M NOT GOING FAR.
SO I STILL AM ON THE ACD, AND SO
I'LL BE WORKING WITH ALL OF YOU
ALL TO CONTINUE TO ADVOCATE FOR
BRAIN AND MAKE SURE IT GETS ALL
OF THE RESOURCES AND ATTENTION
IT DESERVES.
THANK YOU.
>> APPRECIATE IT, KAV.
SAFE TRAVELS.
SO THAT WRAPS UP OPEN SESSION.
SUSAN, DO YOU WANT TO WRAP
THINGS UP AND LET PEOPLE KNOW
WHEN AND WHERE TO RECONVENE FOR
CLOSED SESSION?
>> RIGHT.
CLOSED SESSION STARTS AT 2:30,
HAVE YOU 20 MINUTES.
IT'S A DIFFERENT LINK.
SO YOU NEED TO GET ON FOR THE
OTHER LINK WHICH IS FOR
GOVERNMENT EMPLOYEES, FTEs,
MEMBERS OF THE WORKING GROUP.
WE'LL TALK TO YOU.
>> THANKS, EVERYBODY.
SEE YOU IN A BIT.
[END OF PROGRAM]