I WANT TO WELCOME YOU TO THE
24th MEETING OF THE BRAIN
MULTI-COUNCIL WORKING GROUP, I'M
KRISTIN DUPRE, SPECIALIST, TODAY
FILLING IN FOR DR. SUSAN WEISS.
WE THANK YOU FOR YOUR TIME AND
CONTRIBUTIONS TO THIS EFFORT, AS
ALWAYS.
THE MEETING TODAY WILL BEGIN
WITH AN OPEN SESSION, WHICH IS
BEING VIDEOCAST AND RECORDED.
AND WILL SUBSEQUENTLY BE ARE
ARCHIVED.
TODAY WE BEGIN WITH AN UPDATE
FROM DIRECTOR JOHN NGAI,
DISCUSSING THE CURRENT STATE OF
THE BRAIN INITIATIVE.
AFTER JOHN'S UPDATE, DR.
CHRISTINE GRADY WILL SUMMARIZE
INTERESTING DISCUSSIONS THAT
OCCURRED DURING YESTERDAY'S
BRAIN NEUROETHICS MEETING.
WE'LL ROUND OUT THE OPEN SESSION
WITH A TALK FROM DR. JOHN
MANSEL, DESCRIBING THE ROLE OF
THE LOCUS COERULEUS IN VISUAL
SPATIAL ATTENTION.
WE HAVE A NEW MCWG MEMBERS AND
EX OFFICIOS JOHN WILL FROW. --
WILL INTRODUCE.
I THANK DR. PUBLIC MARKOWITZ,
OUR IARPA REPRESENTATIVE, ON
SERVED FOR FIVE YEARS FROM 2017
TO LAST AUGUST IN 2022.
HE ALSO SERVED ON THE NIH BRAIN
WORKING GROUP 2.0 FROM 2018 TO
2019, A PROGRAM MANAGER AT
IARPA, LEADING AN EFFORT CALLED
MICRONS, THE LARGEST PETABYTE
EXTANT DATE SET OF CO-REGISTERED
DATA FROM THE MAMMALIAN BRAIN.
DAVID WAS A GREAT COLLEAGUE WHO
IS ACTIVE AND CONTRIBUTOR TO THE
BRAIN INITIATIVE, MOVED ON TO
NEW ENDEAVORS OUTSIDE OF THE
FEDERAL GOVERNMENT AND WE WISH
HIM THE BEST.
WE THANK HIM FOR ALL OF HIS
CONTRIBUTIONS TO "BRAIN."
I HAVE A FEW MORE OPENING
REMARKS, AND SOME HOUSEKEEPING
ITEMS FOR US.
AS MOST OF YOU KNOW, THE MCWG IS
NOT A FORMAL ADVISORY GROUP
UNDER THE FEDERAL ADVISORY
COMMITTEE ACT, FACA, ESTABLISHED
BECAUSE OF THE RECOGNIZED NEED
FOR DIVERSE EXPERTISE IN
DISCIPLINES TO ASSESS RESEARCH
BEING SUPPORTED BY THE BRAIN
INITIATIVE, SOME MEMBERS SERVE
ON THE NIH ADVISORY COUNCILS
EVER TEN PARTICIPATING
INSTITUTES AND CENTERS.
WE HAVE ADDITIONAL AT-LARGE
MEMBERS APPOINTED TO SUPPLEMENT
THE GROUP, WORKING GROUP
EXPERTISE, AND SEVERAL EX
OFFICIO MEMBERS FROM DARPA, FDA,
IARPA, NSF, FOR NIH'S FEDERAL
PARTNERS, AND JOHN WILL ANNOUNCE
A NEW NON-FEDERAL EX OFFICIO
MEETING TODAY.
WE DEPEND ON MCWG FOR OVERSIGHT,
FOR FEEDBACK ON WHAT WE REFER TO
AS CONCEPT CLEARANCES THAT ARE
EXPECTED TO LEAD TO FUNDING
ANNOUNCEMENTS AND FUNDING
OPPORTUNITIES, AND IN THE CLOSED
SESSION WE LOOK FOR INPUT ON
FUNDING PLANS.
IN CLOSED SESSION FOR MCWG
MEMBERS AND FEDERAL GOVERNMENT
EMPLOYEES, I WILL GO OVER
OPERATING PROCEDURES.
OPEN SESSION TODAY IS
ANTICIPATED TO END AROUND 1:30
P.M. EASTERN TIME, WE'LL HAVE A
SHORT 30-MINUTE BREAK AND THEN
WE'LL BEGIN THE CLOSED SESSION
AROUND 2:00 P.M. EASTERN TIME.
NOTE THERE WILL BE A DIFFERENT
LINK FOR THE CLOSED SESSION,
WHICH AGAIN IS FOR MCWG MEMBERS,
AND OUR EX OFFICIOS AND
GOVERNMENT EMPLOYEES.
IF YOU ARE AN MCWG MEMBER AND
HAVE NOT READ, SIGNED, RETURNED
YOUR CONFLICT OF INTEREST FORM
TO US, DO SO NOW BEFORE THE
CLOSED SESSION BEGINS.
AGAIN, THE OPEN SESSION IS BEING
VIDEOCAST AND RECORDED LIVE FOR
FUTURE VIEWING.
HOUSEKEEPING, DURING SLIDE
PRESENTATIONS PLEASE MUTE YOUR
LINE, DURING DISCUSSION WE
WELCOME YOU TO TURN ON YOUR
VIDEO IF POSSIBLE, AND IF YOU
HAVE IT PLEASE USE THE RAISE
HAND OPTION, IF YOU HAVE
QUESTIONS, WE WILL CALL ON YOU
TO UNMUTE YOURSELF.
WE WILL DO OUR BEST TO MONITOR
THE CHAT TODAY.
IF YOU EXPERIENCE TECHNICAL
DIFFICULTIES, READ OUT TO SHERRY
AND DEAN SO WE CAN SUPPORT YOU.
YOU CAN PUT THEIR INFO IN THE
CHAT AS WELL FOR YOU.
FINALLY, I WANT TO THANK THE
STAFF WHOSE HARD WORK WENT INTO
PREPARING FOR THIS MEETING AND
OUR COMPANION MEETING YESTERDAY,
THE NEUROETHICS WORKING GROUP
MEETING.
IN PARTICULAR I WOULD LIKE TO
THANK DEB FREEN ERICR, MICHELLE
PEARSON, TOYA ROGERS, DR. NINA
SHUE AND DR. SASKIA HENDRIKS,
COLLEAGUES I'M LUCKY ENOUGH TO
WORK WITH, ALONG WITH THE
FANTASTIC NIH "BRAIN" TEAMS,
PROGRAMMATIC STAFF, COLLEAGUES
IN THE OFFICE OF BRAIN DIRECTOR,
AND OUR BRAIN LEADERSHIP.
SO WITH THAT I WILL TURN THINGS
OVER TO OUR BRAIN LEADERSHIP,
DR. JOHN NGAI.
>>THANKS, KRISTIN.
THANKS FOR STEPPING IN TO MANAGE
TODAY'S MEETING AND FOR ALL THAT
YOU DO TO MAKE THESE MEETINGS
WORK WELL, TOGETHER WITH OUR
GREAT STAFF.
I'LL THANK EVERYBODY ALL AT ONCE
NOW AND CALL OUT A FEW PEOPLE AS
WE GET FURTHER DOWN THE LIST.
SO IT'S A PLEASURE TO BE HERE
WITH YOU TODAY.
SORRY WE CANNOT BE IN PERSON,
BUT AS WE SAY, WE'LL GET 'EM
NEXT TIME, RIGHT?
OKAY.
SO, HERE IS -- ARE PEOPLE SEEING
THE CORRECT VERSION OF MY
SLIDES?
I HOPE, YEAH?
>>LOOKS GOOD.
>>SOMEBODY BLINK TWICE.
TERRIFIC.
I WANT TO GIVE A BRIEF UPDATE.
I'LL BE TALKING ABOUT AS KRISTIN
MENTIONED NEW MEMBERS WHO CAME
ON BOARD TO JOIN US ON MCWG,
GIVE UPDATES ON FOLKS ON THE
STAFF, NEW LEADERSHIP POSITIONS,
AS WELL AS SOME RECENT HONORS
AND EVENTS WITH MEMBERS OF OUR
BRAIN COMMUNITY.
I'LL ALSO TALK ABOUT CURRENT
STATUS OF SOME OF THE PROJECTS,
FOUNDING OPPORTUNITIES, AND IF
THERE'S TIME I'LL HIGHLIGHT A
FEW COOL SCIENCE PAPERS THAT
HAVE COME OUT SINCE WE LAST MET.
OKAY, SO FIRST AND FOREMOST,
WELCOME.
I'D LIKE TO WELCOME DR. HUGO
BELLEN REPRESENTING NICHD,
BAYLOR COLLEGE OF MEDICINE, VERY
WELL KNOWN FOR HIS WORK IN
NEURAL DEGENERATION,
NEUROGENETICS AND TECHNOLOGY
DEVELOPMENT.
WE'VE NOT HAD A CHANCE TO TALK
BUT I LOOK FORWARD TO WORKING
WITH YOU IN THE YEARS TO COME.
DELIGHTED TO WELCOME JEN FRENCH,
FOUNDER AND EXECUTIVE DIRECTOR
FOR NEUROTECH NETWORK, A
TERRIFIC ADVOCATE FOR PERSONS
WITH IMPAIRMENTS WHO NEED ACCESS
TO A -- CONTINUING ACCESS TO
TECHNOLOGIES TO GET GAIN BETTER
QUALITY OF LIFE AND WE'RE
LOOKING FORWARD TO TAPPING INTO
HER EXPERIENCE IN THIS FIELD TO
REALLY GIVE THE VERY IMPORTANT
PERSPECTIVE OF THE PEOPLE THAT
WE ARE IN THE END TRYING TO HELP
WITH OUR NEW AND DEVELOPING
TECHNOLOGIES.
VERY HAPPY TO WELCOME AMY
BERNARD AS EX OFFICIO MEMBER
REPRESENTING THE BRAIN
INITIATIVE ALLIANCE, AN ALLIANCE
OF FEDERAL AND NON-FEDERAL
PARTNERS IN BRAIN INITIATIVE
SPACE.
MANY OF YOU KNOW OR WORKED WITH
AMY IN YEARS PAST.
CURRENTLY SHE'S DIRECTOR OF LIFE
SCIENCES AT THE KAVLI
FOUNDATION, HEAD OF STRATEGY AND
PROGRAMS FOR NANOSCIENCE AND
NEUROSCIENCE DIVISION,
BACKGROUND IN MOLECULAR BIOLOGY,
CELL CULTURE, WELCOME AND
DELIGHTED TO BE WORKING WITH YOU
IN THIS CAPACITY.
I'D LIKE TO WELCOME MR. ROBERT
ROAMER FROM IARPA, AS KRISTIN
MENTIONED DAVID MARKOWITZ MOVED
ON TO THE NEXT CHAPTER OF HIS
REALLY BRILLIANT CAREER AND
STEPPED AWAY FROM IARPA, AND
ROBERT HAS DEEP EXPERIENCE,
ESPECIALLY IN THE AREA OF
CYBERSECURITY, IN MANY AREAS I
HOPE WE CAN CONTINUE TO TOUCH
AND FIND COLLABORATIONS WITH
IARPA AS WE CONTINUE TO MOVE
FORWARD WITH THESE EXCITING
AREAS OF TECHNOLOGY DEVELOPMENT.
AND THE EX OFFICIO MEMBER
REPRESENTING DARPA, GOPAL SARM,
USING MACHINE LEARNING TO MAKE
BETTER AND MORE SCALABLE
PHYSIOLOGICAL MEASUREMENTS THAT
COULD HELP NOT ONLY FOR
BIODEFENSE BUT ALSO TO HAVE
MEDICAL APPLICATIONS AS WE'LL
SEE IN COMING MONTHS AND YEARS.
SO, WITH THESE CHANGES WE ALSO
WANT TO THANK DR. KRISTIN JORDAN
AND DR. DAVID MARKOWITZ, FROM
DARPA AND IARPA, WE APPRECIATE
THEIR CONTRIBUTIONS REPRESENTING
THEIR AGENCIES.
THE OFFICE OF THE BRAIN
DIRECTOR, THIS IS THE HUB ON
THIS MULTI-SPOKED WHEEL THAT
KEEPS THE OPERATION GOING.
I CALL OUT THE TERRIFIC STAFF I
WORK WITH EVERY DAY,
PARTICULARLY NED TALLEY, YOU'RE
ON HERE SOMEWHERE.
NED HAS SERVED AS ONE OF MY
SENIOR ADVISORS FROM THE
MOMENT -- FROM BEFORE I CAME ON
TO NIH, JUST OVER 3 YEARS AGO,
AND IN MANY WAYS HE SERVED AS MY
GUIDE, MY CONCIERGE, CONCIGLIERE
SORTING OUT THINGS WORK AND
COULD WORK AROUND NIH, BUILDING
UP PROGRAMS WE'RE WORKING WITH
TODAY.
NED DECIDED LAST YEAR HIS
CALLING WAS TO SET UP PROGRAMS,
PRINCIPAL ARCHITECT BEHIND THE
BRAIN CONNECTS PROGRAM, WHICH
YOU'LL BE HEARING ABOUT IN
GREATER DETAIL IN CLOSED
SESSION, WE'LL BE DISCUSSIONS OR
YOU WILL BE DISCUSSING THE FIRST
OF THE PAY PLANS AROUND THIS
EXCITING PROJECT.
NED, THANKS FOR YOUR HELP.
GLAD YOU'RE STILL VERY MUCH
INVOLVED IN "BRAIN" IN A
DIFFERENT CAPACITY, I'M SURE
YOU'LL FIND GREAT FULFILLMENT IN
WHAT YOU'RE DOING NOW.
BRAIN INITIATIVE IS ORGANIZED
AROUND NINE TEAMS, SHOWN HERE.
WE'VE HAD A LITTLE BIT OF
TURNOVER, GOOD TURNOVER IN TERMS
OF BRINGING IN NEW LEADERSHIP TO
LEAD THESE TEAMS.
SO I'D LIKE TO WELCOME AS NEW
TEAM CO-LEADS AARON QUINLAN, DR.
IVANA GRAKOWIK, DR. NINA SHUE,
FAMILIAR TO MANY OF YOU, TAKEN
OVER AS CO-LEAD OF TEAM N, AND
DR. MAURICIO RANGEEL GOMEZ, NEW
LEAD FOR TEAM E, SO WELCOME,
DOCTORS, FOR TAKING ON THESE
IMPORTANT LEADERSHIP
OPPORTUNITIES.
MAURICIO IS STEPPING IN TO
REPLACE GRACE WHO HAS GONE ON TO
BETTER THINGS, PURSUING A
PASSION IN MACHINE LEARNING AND
ARTIFICIAL INTELLIGENCE, IN
TRANS-NIH PROGRAMS, SHE'S BEEN
REALLY COMMITTED TO BRINGING
BETTER THEORETICAL AND
COMPUTATION CAL TOOLS INTO THE
BRAIN INITIATIVE.
HEE SHE WAS BEHIND THEORIES,
MODELS AND METHODS PART OF THE
PORTFOLIO.
GOOD NEWS, GRACE WILL STILL BE
PART OF THE BRAIN INITIATIVE,
WORKING ON OUR BEHALF, BUT
DECIDED TO STEP ASIDE AND FOCUS
LEADERSHIP ENERGIES ON THESE
OTHER LARGER -- LARGE TRANS-NIH
INITIATIVES.
AND AGAIN THANK YOU TO ALL THE
MANY CONTRIBUTORS.
THIS IS OUR MOST UPDATED LIST.
SOMEBODY ALWAYS E-MAILS ME
AFTERWARDS AND SAYS YOU MISSED
MY NAME.
IF I DID, LET ME KNOW AND WE'LL
CORRECT IT.
REALLY GREAT FOLKS WHO GIVE
GREAT PASSION, ENERGY, AND
INSIGHT INTO ALL THAT WE DO THAT
MAKES THE INITIATIVE WHAT IT IS.
THANK YOU ALL FOR ALL THE GREAT
WORK ON BEHALF OF "BRAIN."
OKAY.
I WANT TO GIVE A VERY BRIEF
OVERVIEW OF OUR BUDGET
SITUATION.
SO, AS I THINK MOST OF US KNOW,
THE PRESIDENT AT THE END OF LAST
YEAR FINALLY SIGNED THE 2023
BUDGET THAT FUNDS THE GOVERNMENT
THROUGH SEPTEMBER 30 OF THIS
YEAR.
AND "BRAIN" WAS FORTUNATE TO
RECEIVE A NICE $60 MILLION
INCREASE, ABOUT A 10% INCREASE
FROM $620 MILLION LAST YEAR TO
$680 MILLION THIS YEAR.
THESE FUNDS COME FROM TWO
SOURCES, BASE FUNDING TO THE TEN
BRAIN ICs, PLUS FUNDS THAT
WERE AUTHORIZED FROM THE 21ST
CENTURY CURES ACT, WHICH BUMP UP
AND DOWN.
WHAT WE'VE DONE IS WE'RE SEEING
A SMOOTHING AS WE CONTINUE ON
THE STEADY INCREASE IN FUNDING
WHICH LETS US CONTINUE TO BUILD
UP THESE LARGE PROGRAMS WHILE
MAINTAINING THE PROGRAMS THAT
ARE REALLY GIVING US GREAT DATA
ABOUT HOW NEURAL CIRCUITS
UNDERLIE BEHAVIOR AS WE MOVE
FORWARD.
WE'RE VERY, VERY EXCITED ABOUT
THIS, THIS ALLOWS US TO KEEP OUR
FOOT ON THE GAS, AS IT WERE, TO
CONTINUE BUILDING TECHNOLOGIES
THAT WILL ASSIST IN THE
UNDERSTANDING OF NEURAL
CIRCUITS.
SO, HOW HAS "BRAIN" DONE OVER
THE YEAR 2022 OR SINCE INCEPTION
IN 2014?
SO, SINCE 2014, WE FUNDED OVER
1100 P.I.s, FROM OVER 200
INSTITUTIONS THROUGH ALMOST
1,000 AWARDS.
THEY HAVE BEEN QUITE PROLIFIC,
OVER 6,000 PUBLICATIONS, IN A
VARIETY OF JOURNAL TIMES, NOT
ONLY IN NEUROSCIENCES BUT LIFE
SCIENCES, ALSO STRETCHING INTO
ENGINEERING, COMPUTATION, AND
PHYSICAL SCIENCES.
WORD CLOUD SHOWS EMPHASIS ON
NEURONS, WE DO HAVE A PORTFOLIO
ON NON-NEURON CELLS, WORRY NOT,
BUT EMPHASIS ON NEURONS, MODEL
SYSTEMS, HUMANS.
YOU CAN SEE IF YOU CAN FIND YOUR
FAVORITE WORD.
AGAIN, THE PUBLICATIONS HAVE
BEEN HOLDING STEADY, A LITTLE
DROP FROM 2021 TO 2022.
WE LOOKED INTO THIS A BIT.
THERE'S BEEN A SIMILAR DROP IN
PUBLICATIONS FUNDED BY NIH
GRANTS OVERALL IN THE
NEUROSCIENCE SPACE SO I DON'T
THINK THIS IS A BRAIN-SPECIFIC
ANOMALY.
THERE'S A CORRELATION WITH THE
PANDEMIC.
I WOULDN'T CITE ANY CAUSATION.
WE'LL SEE HOW WE'RE DOING.
BUT STILL I THINK IT'S BEEN A
REMARKABLY PROLIFIC GROUP.
I THINK PUBLISHING IMPACTFUL AND
IMPORTANT SCIENCE AS WE GO
ALONG.
SO OVERALL WE'RE VERY PLEASED
WITH THE PROGRESS HERE.
OKAY.
LET'S TALK A BIT ABOUT
SIGNIFICANT EVENTS IN OUR BRAIN
COMMUNITY.
SO IT'S ALWAYS NICE TO HAVE
FOLKS IN OUR MIDST CELEBRATED.
THIS YEAR'S PRIZE WAS AWARDED TO
LARRY, EMORY, TERRY AND HINE AS
PIONEERS IN THE FIELDS OF
COMPUTATIONAL AND THEORETICAL
NEUROSCIENCE.
BOTH LARRY AND EMORY HAVE
PREVIOUSLY SERVED AS MEMBERS OF
THE MULTI-COUNCIL WORKING GROUP.
EMERY AND TERRY WERE
CONTRIBUTORS TO THE BRAIN 2025
REPORT, AND HAIM IS A CURRENT
GRANTEE IN OUR BRAIN CIRCUITS
PORTFOLIO, I BELIEVE ALSO SERVED
ON THE ADVISORY PANELS FOR OTHER
BIG PROJECTS THAT WE'RE
CONDUCTING.
CONGRATULATIONS TO THEM.
IT'S GREAT TO SEE RECOGNITION
FOR THIS AMAZING BODY OF WORK
THEY EACH HAVE CONTRIBUTED TO
THE FIELD.
FOUR BRAIN GRANTEES WERE ELECTED
INTO THE NATIONAL ACADEMY OF
INVENTORS FOR THEIR INVENTIONS,
THEY HAVE ALL MADE REALLY
TERRIFIC CONTRIBUTIONS HERE.
WE'RE VERY PROUD TO HAVE THEM IN
OUR MIDST.
RECENTLY THE NATIONAL ACADEMIES
OF SCIENCES ANNOUNCED ANOTHER
SET OF AWARDS, AND SHE WAS
AWARDED FOR UNDERSTANDING CELL
TYPES AND COMPLEXITY IN THE
NERVOUS SYSTEM, YOU KNOW
HONORINGKUI ZENG WORK WELL,
BEHIND THE BRAIN ATLAS PROJECT
AND WE LOOK FORWARD TO
DISCOVERIES FROM HER AND HER
GROUP.
CONGRATULATIONS.
LAST NIGHT I SAW ON TWITTER MCG
MEMBER AWARDED JAPAN PRIZE IN
LIFE SCIENCES FOR PIONEERING
WORK IN DEVELOPING OPTOGENETIC
TOOLS FOR DISSECTING AND
UNRAVELING NEURAL CIRCUIT
FUNCTIONS, HERE IS KARL IN HIS
ELEMENT.
I DON'T KNOW IF HE'S HERE BUT
CONGRATULATIONS.
>>THANKS, JOHN, APPRECIATE IT.
>>WELL DESERVED HONOR.
YOU PROBABLY ARE ACCUMULATING A
STACK OF THESE, BUT WE'RE VERY,
VERY HAPPY FOR YOU.
OKAY.
IN VERY SAD NEWS OVER THE
WEEKEND WE LEARNED THAT WE LOST
KRISHNA AFTER A BATTLE WITH
CANCER, AN INVESTIGATOR AND LYNN
PROFESSOR OF ENGINEERING AT
STANFORD UNIVERSITY.
HE WAS ALSO DIRECTOR OF NEURAL
PROSTHETIC SYSTEMS LAB AND
CO-DIRECTOR OF TRANSITIONAL LAB
WITH JAMIE HENDERSON.
KRISHNA WAS A BRILLIANT
NEUROSCIENTIST WHO STUDIED MOTOR
CONTROL, PIONEER IN DEVELOPMENT
OF BRAIN-COMPUTER INTERFACE,
NOTABLY THOSE SUPPORTING SPEECH
AND LANGUAGE PROSTHETIC DEVICES
THAT ALLOWED PARALYZED
INDIVIDUALS TO COMMUNICATE.
SOME OF THESE ADVANCES I
HIGHLIGHTED HERE AND I'M SURE
MANY OF YOU HAVE SEEN THE FRUITS
OF KRISHNA'S WORK, TRULY
BRILLIANT.
FROM THE OUTPOURING OF TRISH
--
TRIBUTES, HE WILL BE REMEMBERED
AS A GENUINELY KIND AND GIVING
PERSON WHO TOUCHED WITH GRACE,
HUMILITY AND HUMANITY THE LIVES
OF MANY INCLUDING MYSELF.
HE LEAVES BEHIND AN AMAZING
LEGACY, WE'LL MISS HIM BUT I
EXPECT THAT THROUGH THE DIASPORA
OF THE MANY PEOPLE HE TOUCHED
WE'LL SEE GREAT WORK COMING OUT
FROM FOLKS THAT WORKED WITH HIM.
VERY SAD NEWS BUT WE WERE
FORTUNATE TO HAVE HIM IN OUR
MIDST FOR THE TIME THAT WE DID.
OKAY.
SO, SOME EVENT RECAPS SINCE WE
LAST MET IN MAY.
OR WHENEVER IT WAS.
OKAY.
LAST YEAR.
WE HAD THE NEXT GENERATION OF
NIH BRAIN INITIATIVE LEADERS
MEETING.
VIRTUAL AGAIN.
BACK IN OCTOBER, SORRY.
AND THIS BROUGHT TOGETHER OUR
TRAINEES FROM ACROSS THE RANGE
OF BRAIN INITIATIVE-FUNDED
TRAINING MECHANISMS, F32s, T9
9, R00s, D SPAN AWARDEES,
TRYING TO BUILD COMMUNITY, GREAT
TO HAVE FUNDING BUT I THINK THE
INTANGIBLE VALUE ADD IS BEING
ABLE TO BUILD COMMUNITY FOR
PEER-TO-PEER MENTORING, A
TERRIFIC EVENT.
PERSPECTIVES GIVEN FROM RECENTLY
INDEPENDENT JUNIOR
INVESTIGATORS, AS WELL AS SENIOR
SCIENTISTS, BOTH ELBA SERRANO
AND TED ABEL, AND GAVE FOLKS AN
OPPORTUNITY TO NETWORK SO WE'RE
HOPING ONE DAY TO HAVE THIS
AGAIN IN PERSON BUT I THINK
THERE'S STILL A HUGE BENEFIT IN
US MEETING VIRTUALLY.
I HAD THE OPPORTUNITY TO BRIEF
MEMBERS OF CONGRESS ON THE BRAIN
INITIATIVE TO EMPHASIZE THE
IMPORTANCE OF KEEPING US FUNDED
AT A HEALTHY LEVEL.
THIS WAS AN EVENT THAT WAS
SPONSORED BY THE AMERICAN BRAIN
COALITION AND AMERICAN ACADEMY
OF NEUROLOGY.
AND HELD WITH THE CONGRESSIONAL
NEUROSCIENCE CAUCUS, AND I
THINK, I HOPE, THAT WE WERE ABLE
TO SHOW THEM ABOUT THE GREAT
STRIDES WE'RE MAKING IN THE
NEUROSCIENCE SPACE, DELIVERING
IMPACTS TO HUMANS TODAY WHILE
BUILDING A RUNWAY FOR THE FUTURE
CURES TOMORROW.
AND SO FAR BASED ON THE RESPONSE
WE'VE GOTTEN WITH OUR BUDGET I
WOULD LIKE TO THINK THAT THE
FIELD IS DOING A GREAT JOB IN
SHOWING THEM THAT THEIR
INVESTMENTS HAVE BEEN WELL
SPENT.
END OF LAST YEAR A FANTASTIC
TWO-DAY WORKSHOP WAS PUT
TOGETHER ON HIGH-THROUGHPUT
IMAGING TECHNOLOGIES FOR
CHARACTERIZING BRAIN CELL TYPES
AND CONNECTIVITY.
THE IDEA TO BENCHMARK LARGE
SCALE BRAIN CELL ATLAS
TECHNOLOGY TO IDENTIFY UNMET
NEEDS, STREAMLINE THE PIPELINE,
TO FIND GOALS FOR DATA SHARING,
SCALABLE COMPUTING, REUSE BY THE
COMMUNITY.
I THINK THIS WAS A TERRIFIC
OPPORTUNITY TO SEE WHAT'S OUT
THERE, STATE OF THE ART, AND I
HOPE THAT IT HELPED FOLKS OUT
THERE FIGURE OUT HOW BEST TO
ALIGN THEMSELVES WITH SOME OF
OUR GOALS IN THE UPCOMING FOA
DEADLINES.
OKAY.
REMINDER TO SAVE THE DATE, JUNE
12-12, DATES FOR THE 9th BRAIN
INITIATIVE MEETING; JANE 12-13.
WE'RE WORKING OUT THE DETAILS.
AS SOON AS WE HAVE THINGS WORKED
OUT THERE WILL BE A MASS E-MAIL.
DON'T IGNORE IT.
IF YOU CAN ATTEND IT WOULD BE
AWESOME.
THERE WILL BE AT LEAST A VIRTUAL
COMPONENT, WORKING HARD TO SEE
IF WE CAN HOLD ANYTIME PERSON AS
WELL AS HYBRID SO STAY TUNED.
ANOTHER UPCOMING EVENT IS THE
NEXT BRAIN BEHAVIOR
QUANTIFICATION AND
SYNCHRONIZATION WORKSHOP, HERE
WE'RE GOING TO EMPHASIZE THE
CURRENT STATE OF THE ART OF
SENSOR TECHNOLOGIES AND HOW THEY
CAN BE USED IN THIS SPACE.
IT WILL BE CO-CHAIRED BY JOHN
ROGERS FROM NORTHWESTERN, AND
J.C. CIAO, MORE DETAILS TO COME.
TEAM E BRAIN CIRCUITS PROGRAM
WILL BE HOSTING A TEAM SCIENCE
WEBINAR COMING ON FEBRUARY 15,
THE GOAL HERE IS TO SHARE THE
INITIATIVE TO TEAM SCIENCE, TO
GIVE FOLKS AND IDEA ABOUT WHAT
IT ENTAILS AND HOW THEY MIGHT
ALIGN THEMSELVES WITH IT.
JIM AND KAREN WILL BE
PRESENTING.
I SHOULD EMPHASIZE ANYONE
INTERESTED IN BRAIN INITIATIVE
TEAM SCIENCE, WHAT WE'RE DOING,
IS MORE THAN WELCOME TO ATTEND
AND AS WELL TO APPLY FOR UO1 AND
U19 GRANTS, WE ACTIVELY
ENCOURAGE INDIVIDUALS WITH
DIVERSE PERSPECTIVES TO APPLY
FOR THESE TEAM SCIENCE
OPPORTUNITIES.
AGAIN, YOU DO NOT HAVE TO BE A
BRAIN GRANTEE TO ATTEND THE
WEBINAR.
HOPEFULLY WE CAN GET THE WORD
OUT AND START REACHING A WIDER
SWATH OF NEUROSCIENCE COMMUNITY
TO BRING IN MORE AND DIVERSE
PERSPECTIVES INTO THE PORTFOLIO.
I WANT TO GIVE A BRIEF UPDATE ON
THE PLAN FOR ENHANCING DIVERSE
PERSPECTIVE, NEW REQUIREMENT IN
BRAIN FOAs.
THEY HAVE BEEN INCORPORATED INTO
29 CURRENT BRAIN FOAs, AS THEY
GET REISSUED THEY WILL BE
INCORPORATED.
WE HAVE A NUMBER FOR YOUR
CONSIDERATION LATER IN CLOSED
SESSION.
AND THE PDP CONTINUES TO BE
ADOPTED WIDELY ACROSS NIH.
RIGHT NOW IT IS CURRENTLY IN 61
PROGRAM ANNOUNCEMENTS, RFAs,
ACROSS NIH.
THE LIST IS GROWING.
SO IT WILL BE VERY INTERESTING
AND EXCITING TO SEE HOW THIS
DEVELOPS OVER TIME AND TO BE
ABLE TO MEASURE AND QUANTIFY HOW
THIS WILL HOPEFULLY IMPACT THE
DIVERSITY OF GRANTEES FUNDED NOT
JUST BY THE BRAIN INITIATIVE BUT
ALSO NIH MORE BROADLY.
SO WE'LL KEEP YOU POSTED ON
PROGRESS THERE AS WE GET MORE
DATA ON THE EFFECTS OF THE PDP.
I WANT TO TOUCH BRIEFLY ON OUR
BRAIN 2.0 TRANSFORMATIVE
PROJECTS, ALL UNDERWAY, THE CELL
ATLAS PROGRAM IS FOCUSING ON BIG
BRAINS.
THE FIRST SET OF AWARDS WERE
MADE IN MAY COUNCIL, NOW ACTIVE.
VERY EXCITING TIMES THERE.
WE HAVE A SECOND RECEIPT DATE
COMING UP IN ACTUALLY THIS
COMING MONTH, SO STAY TUNED FOR
THAT.
THE ARMAMENTARIUM PROJECT FOR
DEVELOPING TOOLS FOR PRECISION
CELL ACCESS IN THE BRAIN, THE
SECOND ROUND OF TOOLS AWARDS
WERE MADE IN THE LAST COUNCIL
ROUND, AND THE SECOND ROUND OF
CAPACITY BUILDING APPLICATIONS
HAVE BEEN REVIEWED AND WE'LL BE
DISCUSSING THOSE IN CLOSED
SESSION TODAY.
THE BRAIN CONNECTIVITY PROJECT,
BRAIN CONNECTS, FOA WAS ISSUED
AGAIN, WE HAVE ANOTHER -- LET ME
BACK UP.
WE'RE IN THE PROCESS OF
CONSIDERING FUNDING THE FIRST
SET OF APPLICATIONS AND THERE'S
ANOTHER ROUND OF RECEIPT DATES
COMING IN, IN JUNE, OF 2023.
SO I JUST WANT TO TOUCH ON A FEW
OF THESE NEW FOAs COMING OUT.
THE ARMAMENTARIUM, THE GOAL HERE
WAS TO DEVELOP NOT ONLY DELIVERY
TOOLS BUT ALSO PAYLOADS, OR
EFFECTORS, TO PUT THESE TOGETHER
TO DEVELOP A REALLY
COMPREHENSIVE TOOL KIT FOR
ACCESSING, MODULATING, AND
MONITORING CELLS WITH GREATER
AND GREATER PRECISION IN NEURAL
CIRCUITS, TOWARD THE GOAL OF
UNDERSTANDING THE NEURAL CIRCUIT
BASIS OF BEHAVIOR.
SO, WE ISSUED A UM1, A LARGE
GRANT PROGRAM, TO DEVELOP AND
ENGINEER OPTIMIZE MOLECULAR
TECHNOLOGIES FOR FUNCTIONAL
DISSECTION OF NEURAL CIRCUITS,
THIS WILL BE INCORPORATED INTO A
LARGER CONSORTIUM OF
INVESTIGATORS WITH FUNDING FOR
DIFFERENT BRAIN MECHANISMS TO
WORK TOGETHER IN PRE-COMPETITIVE
SPACE WITH GOAL OF GETTING
BETTER TOOLS OUT TO THE
COMMUNITY ON A MORE RAPID
TIMELINE.
SO STAY TUNED FOR THAT.
AGAIN, THE FIRST APPLICATION DUE
DATE FOR THIS UM1 MOLECULAR
PAYLOAD CENTERS WILL BE IN JUNE
OF THIS YEAR, THESE WILL BE
FIVE-YEAR PROJECTS.
BRAIN BEHAVIOR AND
SYNCHRONIZATION PROGRAM IS
LAUNCHED, DUE DATES NEXT MONTH,
FIRST FOCUSING ON HUMANS, AND
THEN NON-HUMAN MODELS.
THIS WILL BE A TERRIFIC PROJECT
GIVEN SOME TECHNOLOGIES THAT ARE
BEING DEVELOPED IN AND AROUND
THE BRAIN SPACE.
HERE'S A SUMMARY OF NEW FUNDING
OPPORTUNITIES ALREADY MENTIONED.
THE BBQS RFAs, THE MOLECULAR
PAYLOADS RFA.
I DON'T QUITE HAVE TIME TO
MENTION TO YOU IN GREAT DETAIL
THE TRANSFORMATIVE BRAIN
NON-INVASIVE IMAGING TECHNOLOGY
INVOLVEMENT RFA, THE IDEA HERE
IS TO IDENTIFY INTERESTING AND
POTENTIALLY TRANSFORMATIVE
TECHNOLOGIES IN AN EARLY PHASE
AND IF IT SHOWS PROMISE WILL GO
TO FURTHER DEVELOPMENT IN THE
UH3 PHASE.
WE HAVE RECENT REISSUES FOR THE
BICAM PROJECT AND THEORIES AND
METHODS PROGRAM.
THIS IS WHAT WE HAVE IN TERMS OF
FUNDING OPPORTUNITIES.
I WANT TO REMIND YOU OF THE R25
SHORT COURSES IN RESEARCH
EDUCATION, ENCOURAGING FOLKS TO
USE THIS TO HELP TEACH DIVERSE
COHORT OF TRAINEES ABOUT SOME OF
THE TECHNOLOGIES THAT ARE BEING
DEVELOPED IN AND AROUND THE
BRAIN INITIATIVE.
AND THE DETAILS ARE HERE.
IT'S LIMITED TO $250,000 DIRECT
COST PER YEAR, AND WE HAVE THE
DEADLINE COMING UP ON YEARLY
BASIS.
NEXT ONE COMING UP VERY SOON, IN
FEBRUARY OF THIS YEAR, BUT WE'LL
HAVE ANOTHER RECEIPT DATE IN THE
FOLLOWING YEAR IN 2024.
SO PLEASE KEEP THAT IN MIND.
ANOTHER REMINDER MULTIPLE
TRAINING OPPORTUNITIES SUPPORTED
BY BRAIN.
IN TERMS OF GENERAL TRAINING, WE
HAVE OUR F32 POSTDOCTORAL
FELLOWSHIP AND RSAs, WE HAVE
PARTICIPATE IN ADMIN SUPPLEMENTS
FOR REENTRY INTO THE BIOMEDICAL
AND BEHAVIORAL WORKFORCE.
AND THEN IN TERMS OF DIVERSITY
FOCUSED MECHANIC ISMS, WE
PARTNER, CONTINUE TO ACTIVELY
SUPPORT OUR DIVERSITY FOCUS
K99/R00 MECHANISM, WHERE WE
INCLUDE WOMEN AS
UNDERREPRESENTED GROUPS IN THE
BRAIN PORTFOLIO.
WE ALSO HAVE ADMIN SUPPLEMENTS
TO PROMOTE DIVERSITY IN
TRAINEES, AND MANY WILL BE
ENCOURAGED AS FOLKS COME IN, ON
THESE DIVERSITY SUPPLEMENTS
EVENTUALLY WILL APPLY FOR AND BE
COMPETITIVE FOR SOME OTHER
INDIVIDUAL TRAINING AWARDS FOR
THEIR FUTURE PROFESSIONAL
DEVELOPMENT.
AND WE ALSO PARTICIPATE IN THIS
NIH CENTRAL ADMIN SUPPLEMENT
MECHANISM FOR RESEARCH
CONTINUITY AND RETENTION.
YOU CAN READ MORE IF YOU WISH AT
THE FOLLOWING WEBSITE.
YOU CAN ALSO USE THIS SNAZZY QR
CODE IF YOU'RE MORE TECH SAVVY
THAN I AM.
THAT'S WHAT I HAVE TO TELL YOU
SO FAR ABOUT OUR FUNDING AND
TRAINING OPPORTUNITIES.
I THINK, KRISTIN, ARE WE DOING
OKAY ON TIME HERE?
>>YES, WE'RE DOING GREAT.
>>OKAY.
GREAT.
LET ME TAKE THIS OPPORTUNITY TO
HIGHLIGHT JUST A COUPLE OF
RECENT INTERESTING PUBLICATIONS,
PUBLISHED FROM BRAIN-FUNDED
INVESTIGATORS.
WE HAVE A TERRIFIC SCIENCE TALK
COMING UP FROM JOHN MANSELL,
SHOULD GET NICE SCIENCE IN TODAY
AS WELL.
I WANT TO TOUCH ON ASTROCYTE
DIVERSITY ACROSS THE CENTRAL
NERVOUS SYSTEM FUNDED IN PART BY
A BRAIN GRANT TO UCLA AND CAL
TECH ON CHARACTERIZING
NON-NEURONAL CELLS.
AND THIS REPRESENTS AN EFFORT
FROM INTERNATIONAL TEAM, A
NUMBER OF PROPERTIES OF
ASTROCYTES ACROSS THE MOUSE
BRAIN REVEALED INTERESTING
PROPERTIES OF ASTROCYTE TO
NEURON RATIO, GENE EXPRESSION
DIFFERENCES, MORPHOLOGY, THAT
SEEM TO VARY ACROSS BRAIN
REGIONS.
AND HERE'S SOME OF THE DATA
HERE.
YOU CAN SEE FOR EXAMPLE WHILE
THE NUMBER OF ASTROCYTES ACROSS
THESE BRAIN REGIONS, THEY
SAMPLED 13, CONSTANT, NEURONS
VARIES, RATIO CHANGES QUITE A
BIT.
THEY FOUND DIFFERENTIALLY
EXPRESSED GENES ACROSS THE
REGIONS.
USED A NICE IMAGING TECHNIQUE,
WIDE FIELD, TO CAPTURE
MORPHOLOGY, QUANTIFY AND
CATEGORIZE THESE ASTROCYTES
ACROSS THE DIFFERENT BRAIN
REGIONS BY MORPHOLOGY, SO
ASTROCYTES FOUND IN DIFFERENT
REGIONS SEEM TO HAVE DIFFERENT
SHAPES AND FORMS.
THE OVERALL SIZE OF THE
ASTROCYTES CORRELATED WITH
EXPRESSION OF CERTAIN
INTERACTING PROTEINS.
YOU CAN SEE THIS, THEY HAVE
LOOKED AT RATIO OF SIZE OF
ASTROCYTES BETWEEN DIFFERENT
REGIONS HERE, CORTEX VERSUS
HIPPOCAMPUS, IDENTIFIED GENES
ENRICHED IN SOME OF THOSE
COMPARISONS.
THE KNOCKDOWN OF TWO OF THESE
GENES USING NICE
ADENO-ASSOCIATED VIRUS DELIVERED
CRISPR/CAS9 TRICK RESULTING IN
REDUCED TERRITORY SIZE OF
ASTROCYTES WHICH SEEM TO AFFECT
THE MOUSE'S PERFORMANCE IN A
BEHAVIORAL MEMORY TASK.
AND QUITE INTERESTINGLY SOME OF
THESE ASTROCYTE-SPECIFIC GENES
ASSOCIATED WITH MORPHOLOGY FOUND
TO BE DOWNREGULATED IN HUMAN
ALZHEIMER'S TISSUE AND MOUSE
MODELS OF A.D. WHERE THE
ASTROCYTE SIZE WAS SMALLER,
GOING TOWARD A BETTER AND DEEPER
CHARACTERIZATION OF THESE
NON-NEURONAL CELLS IN THE BRAIN,
AND HOPEFULLY GIVING INSIGHT
INTO THE ROLE THEY PLAY NOT ONLY
IN THE NORMAL HEALTHY BRAIN BUT
HOW THEY MIGHT INITIATE OR
CONTRIBUTE TO DISEASE
PROGRESSION IN CONDITIONS SUCH
AS ALZHEIMER'S AS WELL AS OTHER
DEGENERATIVE CONDITIONS, A COOL
PAPER THAT CAME OUT LAST YEAR.
A DIFFERENT TYPE OF STUDY, THIS
IS A STUDY FROM CORY MILLER,
UCSD, INTERNATIONAL
COLLABORATION WITH FOLKS I
BELIEVE IN BRAZIL.
THE RESEARCHERS CHARACTERIZE
CAPTURE BEHAVIOR BY ANALYZING
HIGH DEFINITION VIDEOS.
HERE IS A MARMOSET ON THE TREE
SEARCHING FOR AND CAPTURING
PREY, WHICH BY AND LARGE ARE
INSECTS IN THIS CASE.
THEY FOUND THE MARMOSETS
EMPLOYED ONE OF THREE TACTICS
TYPICALLY FOR PREY CAPTURE.
ONE WAS CAPTURE IN FLIGHT, TO
CAPTURE FLYING INSECTS.
STALK, PAUSE, AND LUNGE, USED TO
CREEP UP ON PREY THAT WAS
TYPICALLY CAMOUFLAGE AND
STATIONARY BUT IF YOU STARTED
THE PREY THEY MIGHT TAKE OFF SO
THEY HAVE TO STALK, PAUSE, LUNGE
AT THEM.
AND MOUTH CAPTURE FOR BASICALLY
IMMOBILE PREY JUST SITTING THERE
WAITING TO BE EATEN, I SUPPOSE.
THEY KIND OF DEFINE THAT.
AND WHAT WAS COOL ABOUT THIS IS
THEY USED THIS SLEEP PROTOCOL
THAT WAS PREVIOUSLY DEVELOPED
FOR MOTION TRACKING AND HERE
THEY USE IT IN A MARKERLESS
MOTION TRACKING, THEY ARE ABLE
TO TRACK MOVEMENTS OF THE
ANIMALS AND THEIR BODY PARTS IN
THE WILD.
THEY USE THIS TO QUANTIFY GAZE
TRACKING AND MOTOR COORDINATION
TO SHOW ACTIVE VISION IS
INTEGRAL TO SUCCESSFUL PREY
CAPTURE IN THESE WILD ANIMALS.
I DON'T KNOW IF YOU CAN FULLY
SEE THIS HERE, BUT HERE IS THE
MARMOSET IN THE TREE.
HERE IS THE MOVEMENT OF THE
INSECT.
HERE IS THE MOVEMENT TRACK OF
THE MARMOSET'S HEAD.
AND YOU CAN SEE RIGHT BEFORE
PREY CAPTURE HERE WHICH IS TIME
ZERO ABOUT A SECOND AND A HALF
BEFORE PREY CAPTURE THERE'S A
STRIKING CORRELATION BETWEEN THE
MOVEMENT OF THE MARMOSET'S HEAD
AND MOVEMENT OF THE INSECT AND
RIGHT BEFORE PREY CAPTURE A VERY
FAST SHIFT IN THE MARMOSET'S
HEAD THAT TRACKS THIS PREY.
AND ON THE RIGHT SHOWS THE
MOVEMENT OF THE ARMS, AS IT'S
REACHING OUT TO GRAB THE PREY
OUT IN THE AIR, AND YOU CAN SEE
THE MOVEMENT IS THERE.
THIS QUANTITATIVE
CHARACTERIZATION IS CRITICAL FOR
UNDERSTANDING NEURAL VERSUS
BEHAVIOR, PRE-SAGES MAN GOALS IN
BBQS PROGRAM AND HOPEFULLY
UNDERSTANDING WHAT'S GOING ON IN
THE WILD CAN DEVELOP BETTER
MODELS FOR UNDERSTANDING THESE
KINDS OF BEHAVIORS IN THE
LABORATORY SETTING.
SO REALLY COOL STUFF FROM THE
MILLER LAB AT UCSD.
OKAY.
SO I'LL WRAP UP TO REMIND YOU
DIFFERENT WAYS OF LEARNING ABOUT
BRAIN.
YOU CAN SUBSCRIBE TO OUR BRAIN
BLOCK, THE NIH WEBSITE, MONITOR
GUIDE NOTICES, BUT MOST
EFFECTIVE WAY TO LEARN WHERE
WHAT'S GOING ON IN BRAIN IS
CONNECT WITH YOUR I.C.'S BRAIN
PROGRAM OFFICER, THEY ARE REALLY
HERE TO ENGAGE YOU, FIND OUT IF
THERE'S A GOOD FIT FOR YOU IN
"BRAIN" OR TO MAKE A FIT HAPPEN,
AND THEY ARE ONE OF YOUR BEST
RESOURCES TO ESTABLISH THAT KIND
OF INFORMATION.
AND, AGAIN, TO REMIND YOU WE
HAVE ABOUT TWO DOZEN FOAs
CURRENTLY AVAILABLE RANGING FROM
CELL TYPES TO CIRCUITS TO
TRANSFORMATIVE PROJECTS.
AND YOU CAN FIND US HERE AT THIS
WEBSITE OR USE THIS SNAZZY QR
CODE.
I TRIED IT THE OTHER DAY.
IT ACTUALLY WORKS.
I'LL LEAVE IT AT THAT.
I THINK WE HAVE A FEW MINUTES
FOR QUESTIONS MAYBE.
>>YES, WE DO HAVE 12 MINUTES
FOR QUESTIONS.
SO, DOES ANYONE HAVE QUESTIONS
OR DISCUSSION POINTS FOR JOHN?
>>THANKS, JOHN, A NICE SUMMARY
OF THINGS GOING ON.
I WANT TO ASK ABOUT THE SHORT
COURSE RFA LOOKS LIKE YOU PUT
THAT ONCE A YEAR, IS THERE A
RATIONALE FOR DOING THAT AT
LEAST TWICE A YEAR OR WHAT ARE
YOUR THOUGHTS ON THAT?
>>WE'RE TRYING TO BALANCE
AVAILABILITY WITH DEMAND, ALSO
STAFF WORKLOAD.
RIGHT NOW LET'S JUST SAY DEMAND
ISN'T YET THERE TO COME IN AT A
GREATER FREQUENCY.
THIS GIVES FOLKS A TIME TO
REVISE AND RESUBMIT IF THEY
DON'T DO WELL THE FIRST TIME
THROUGH.
WE'RE CERTAINLY OPEN TO IT BUT I
DON'T -- AT THIS POINT I'M NOT
SURE THE RECEIPT DATES IS
LIMITING.
PEOPLE NEED TIME TO THINK ABOUT
IT.
I'VE TALKED TO A FEW FOLKS ABOUT
COMING IN FOR THIS AS WELL.
STUNNED INTO SILENCE.
>>OTHER QUESTIONS?
OR DISCUSSION POINTS?
OKAY.
I THINK WE CAN MOVE ON.
DOES THAT SOUND GOOD, JOHN?
>>YEP.
IS CHRISTINE HERE?
>>YEAH, NEXT UP WE HAVE DR.
CHRISTINE GRADY.
SHE DOESN'T NEED AN INTRODUCTION
BUT SHE'S A NURSE BIOETHICIST
AND SENIOR INVESTIGATOR WHO
SERVES AS CHIEF OF THE
DEPARTMENT OF BIOETHICS AT THE
CLINICAL CENTER AT NIH.
CHRISTINE HAS PUBLISHED WIDELY
IN THE BIOMEDICAL AND BIOETHICS
LITERATURE, A TREASURE FOR
BRAIN.
I'LL TURN IT OVER TO CHRISTINE
TO DISCUSS THE NEWG MEETING FROM
YESTERDAY.
>>THANK YOU FOR THE LOVELY
INTRODUCTION, KRISTIN.
I WANTED TO SPEND A MINUTE JUST
TELLING EVERYBODY WHAT THE
NEUROETHICS WORKING GROUP WAS
BECAUSE THERE ARE SOME NEW
MEMBERS TO THIS MCWG, THE GROUP
IS AFFECTIONATELY CALLED NEWG, A
GROUP OF NINE PEOPLE EXPERTS IN
NEUROETHICS AND NEUROSCIENCE.
AND WE WORK TO PROVIDE INPUT
RELATED TO NEUROETHICS TO THE
BRAIN INITIATIVE AND TO THE
MULTI-COUNCIL WORKING GROUP.
IT WAS FORMED AT THE END OF
2015, I'M HONORED TO CO-CHAIR
CURRENTLY WITH DR. NITA
FARAHANY, DISTINGUISHED
PROFESSOR OF LAW AND PHILOSOPHY
AT THE DUKE UNIVERSITY SCHOOL OF
LAW.
AND WE MEET AS A GROUP TWICE A
YEAR, USUALLY IN JANUARY AND
AUGUST, VERY OFTEN JUST THE DAY
BEFORE YOUR GROUP MEETS.
AND THEN OFTEN HAVE TOPICAL
WORKSHOPS THAT WE SCHEDULE WHEN
APPROPRIATE.
OUR CHARGE BASICALLY IS
IDENTIFYING ETHICAL CHALLENGES
IN THE DEVELOPMENT AND/OR
APPLICATION OF BRAIN RESEARCH,
ANTICIPATING AND PROVIDING WAYS
FOR BRAIN TO NAVIGATE ETHICAL
CHALLENGES, PROVIDING
CONSULTATION WHEN APPROPRIATE
AND IDENTIFYING NEUROETHICS
QUESTIONS ADDRESSED THROUGH
FUNDING OPPORTUNITY OR OTHER
MECHANISMS.
AND THEN WHEN APPROPRIATE
PUBLISHING ON KEY ETHICAL
CHALLENGES THAT ARE TIED TO THE
BRAIN INITIATIVE.
SO, MY TASK FOR TODAY IS TO JUST
TELL YOU A LITTLE BIT ABOUT WHAT
OUR MEETING WAS LIKE YESTERDAY.
TO RECAP THAT MEETING, WE HAD A
MEETING YESTERDAY AFTERNOON, IT
WAS VIRTUAL ALSO, AS YOURS IS
TODAY.
JOHN STARTED THE DAY WITH AN
UPDATE FROM BRAIN AND FOCUSED ON
TWO OTHER KINDS OF RECENT
RESEARCH FINDINGS IN BRAIN THAT
RAISED REALLY INTERESTING
ETHICAL CHALLENGES, ONE IS THE
IMPLANTATION OF HUMAN
iPSC-DERIVED ORGANOIDS INTO
MOUSE BRAINS, WHICH REVEALED
SOME FUNCTIONAL CONNECTIONS AND
VASCULARIZATION, AND LEAD TO
SOME REALLY INTERESTING
QUESTIONS.
AND ALSO ANOTHER STUDY, PILOT
STUDY OF TWO PATIENTS DBS IN THE
NUCLEUS ACCUMBENS, DONE TO LOOK
AT CONTROL OF BINGE EATING AND
ACTUALLY FOUND SOME INTERESTING
EFFECTS IN THE TWO PATIENTS THAT
THEY PILOTED.
I WAS FASCINATED BY SOME OF THE
THINGS YOU MENTIONED JUST NOW,
JOHN, IN TERMS OF THE RESEARCH
THAT'S BEING DONE.
SO THERE MAY BE OTHERS THAT HAVE
ETHICAL IMPLICATIONS.
DR. NGAI MENTIONED YESTERDAY A
CALL FOR SUPPLEMENT THROUGH
OFFICE OF SCIENCE POLICY GENERAL
BIOETHICS BUT ALSO WOULD SUPPORT
NEUROETHICS WORK AND HAS IN THE
PAST, THAT MECHANISM HAS
SUPPORTED SOME SUPPORT FOR BRAIN
INITIATIVE PREVIOUSLY, SO THAT'S
SOMETHING THAT'S OPEN AT THE
MOMENT.
AND ALSO DUE IN FEBRUARY, THE
APPLICATIONS FOR THAT
SUPPLEMENT.
WE SPENT THE FIRST HALF OF THE
MEETING REALLY HAVING AN OPEN
SESSION ON HEALTH-RELATED
TECHNOLOGIES THAT AFFECT THE
BRAIN.
WE HAD TWO VERY INTERESTING
PRESENTATIONS, ONE FROM DR.
KRYSTAL AT UCSF WHO PRESENTED ON
A PERSONALIZED USE OF
CLOSED-LOOP NEUROMODULATION AND
INDIVIDUAL TREATMENT-RESISTANT
DEPRESSION, TALKED ABOUT EFFECTS
THEY WERE ABLE TO HAVE ON THIS
PARTICULAR PATIENT AND HOW THEY
MAY EXPAND IT TO OTHER PATIENTS
OF SIMILAR PHENOTYPES.
A SECOND PRESENTATION FROM DR.
VIVIC PANDRANGI, A STUDY FOR
PAIN MANAGEMENT, DECREASING
OPIOID USE IN PATIENTS WHO HAD
HAD HEAD AND NECK SURGERY.
THOSE TWO CASE STUDIES LED TO A
GENERAL DISCUSSION ON SOME OF
THE ETHICAL QUESTIONS RAISED BY
HEALTH-RELATED TECHNOLOGIES THAT
AFFECT THE BRAIN, AND WE
DISCUSSED ACTUALLY WHETHER IT
MATTERS WHAT THE TECHNOLOGIES
ARE, WHETHER THEY ARE DIRECT OR
INDIRECT, WHETHER THEY ARE
INVASIVE OR NOT INVASIVE.
AND LOTS OF DISCUSSION ABOUT
WHETHER OR NOT THE NEUROETHICS
WORKING GROUP COULD DO SOMETHING
CONSTRUCTIVE IN THIS AREA OF
HEALTH EFFECTS ON THE BRAIN.
WE TALKED ABOUT DIFFERENT
BOUNDARIES, HOW TO UNDERSTAND
MECHANISMS, THE ISSUES OF
INDIVIDUALIZATION AND
GENERALIZABILITY, IN STUDIES.
REVERSIBILITY AS CRITERIA AND
NEED TO REVISIT THEMES RAISED IN
THE BRAIN 2.0 NEUROETHICS REPORT
THAT JIM EBERWINE WAS A LEADER
OF FOR INSPIRATION AND SCOPING
WHAT THE NEUROETHICS GROUP,
WORKING GROUP MIGHT DO IN THIS
SPACE.
THAT'S MORE TO BE HAD ON THAT
DISCUSSION.
THERE ARE ANNOUNCEMENTS ON
PROGRAMMATIC PILLARS LAUNCHED AT
THE DANA FOUNDATION.
OECD REPORT, LEADING TO SOME
PRODUCTIVE INTERNATIONAL
CONVERSATIONS.
EFFORTS FROM THE RESEARCH ON
HUMANS CONSORTIUM, PART OF THE
BRAIN INITIATIVE INVESTIGATOR
GROUP, AROUND DATA SHARING AND
DATA REUSE, AND PLANS FOR THE
NEWG TO HAVE A WORKSHOP ON DATA
SHARING AND DATA PRIVACY,
TENTATIVELY PLANNED FOR JULY OF
THIS YEAR.
MORE INFORMATION WILL BE COMING
IN CASE PEOPLE ARE INTERESTED IN
ATTENDING.
AND THEN IN THE CLOSED SESSION,
THE NEUROETHICS WORKING GROUP
HAD DISCUSSION THAT WAS A
CONSULTATION THAT WILL BE
SUMMARIZED AT AN NIMH COUNCIL
MEETING IN THE NEAR FUTURE.
HAPPY TO ANSWER QUESTIONS ABOUT
YESTERDAY'S AGENDA OR THE
NEUROETHICS WORKING GROUP IN
GENERAL, AND THANK YOU FOR
GIVING ME TIME TO TALK TO YOU
ABOUT IT.
>>THANK YOU SO MUCH, CHRISTINE
ARE THERE ANY QUESTIONS OR
COMMENTS?
I KNOW WE HAVE MCWG MEMBERS WHO
ALSO SERVE ON THE NEWG, SO --
>>I ALSO WANT TO ACKNOWLEDGE WE
HAD MANY OTHER NON-NEWG MCWG
MEMBERS, REALLY TERRIFIC, AND
APPRECIATE THEIR CONTRIBUTIONS
TO OUR DISCUSSION YESTERDAY.
>>ABSOLUTELY.
YOU'RE ALWAYS INVITED.
>>ALWAYS, ALWAYS.
>>TED?
KRISTIN, ARE YOU CALLING ON
PEOPLE OR ME IN I DON'T KNOW.
>>IT'S ALL GOOD.
TED?
>>THANKS.
I ENJOYED MEETING YESTERDAY.
IT WAS AN INTERESTING
DISCUSSION.
I HAVE A QUESTION, MAYBE MORE
ABOUT THE BRAIN INITIATIVE,
CONNECTED TO NEWG.
THAT IS THAT WE THOUGHT ABOUT
INCORPORATING NEUROETHICS IN
GRANTS AND IN RESEARCH STUDIES
WHICH I THINK IS TERRIFIC.
I WONDER WHAT'S HAPPENING IN THE
TRAINING SPACE FOR NEUROETHICS
AND IF THOSE TRAINING GRANTS ARE
ELIGIBLE FOR -- I WONDER WHERE
THAT IS IN THE TRAINING SPACE.
SEEMS IT MIGHT BE HARD TO REVIEW
BY EXISTING STUDY SECTIONS AND
SO MY QUESTION WAS ABOUT
TRAINING IN NEUROETHICS AND WHAT
ARE WE DOING ABOUT ING ABOUT TH.
>>I CAPTAIN CITE NUMBERS BUT I
BELIEVE THROUGH SUPPLEMENTS OR
INDIVIDUAL AWARDS.
NINA, CAN YOU SPEAK TO THAT?
>>TED, THERE'S A COUPLE LAYERS,
T32s DON'T HAVE ANYTHING
AVAILABLE IN NEUROETHICS SPACE
BUT AS FAR AS OUR EXISTING BRAIN
INITIATIVE FUNDING MECHANISMS WE
HAVE RECEIVED AND FUNDED SEVERAL
APPLICATIONS THAT ARE IN THE F32
AND K99 SPACE NOW.
IN FACT HAVE A K99 THAT
TRANSITIONED TO R 00 WORKING IN
THE NEUROETHICS SPACE, WE HAVE
SOME THERE AND WE'VE SUPPORTED
SEVERAL INDIVIDUALS ON SOME OSP
SUPPLEMENTS LIKE CHRISTINE
REFERENCED.
WE HAVE SUPPORTED MULTIPLE
PEOPLE EARLY STAGE FACULTY
MEMBER, LATE STAGE POSTDOC,
WANTING TO INTEGRATE NEUROETHICS
INTO THE EXISTING BRAIN
INITIATIVE PROJECTS, AND I KNOW
WE'VE GOT A FEW MORE COMING OUR
WAY AS WELL.
>>YEAH, THANKS, JAY.
IT SEEMS LIKE AN IMPORTANT
OPPORTUNITY AND I WONDER IF
WE'RE GIVING IT ENOUGH AIR TIME
IN TERMS OF TRAINING IN
NEUROETHICS.
>>THAT'S A GOOD POINT, TED.
WE'RE NOT LIMITING OUR END.
WHAT WE'RE LIMITING IS
VISIBILITY IN THE COMMUNITY,
BRINGING FOLKS IN TO APPLY.
I HOPE BY MAY WE'LL HAVE
SOMETHING TO TELL YOU ABOUT
OUTREACH STRATEGIES WE'RE
PUTTING TOGETHER, STRATEGIES FOR
OUTREACH THAT WILL BRING IN
FOLKS FROM DIFFERENT WALKS OF
LIFE, DIFFERENT BACKGROUNDS,
DIFFERENT LOCATIONS.
>>I THINK ALSO WHERE THE DANA
FOUNDATION IS GOING WILL OVERLAP
TOO BECAUSE THEY ARE GOING TO
MORE SOCIETAL ISSUES AND SO THEY
MIGHT VERY WELL OVERLAP.
>>PERHAPS CAROLINE WANTS TO
ADDRESS THAT.
A GREAT OPPORTUNITY FOR
PARTNERSHIPS WITH OUR
NON-FEDERAL PARTICIPANTS.
>>THANK YOU SO MUCH, TED, FOR
BRINGING UP THAT VERY IMPORTANT
QUESTION.
FROM THE DANA FOUNDATION SIDE
THIS WOULD BE AN WE WOULD LOVE
TO PARTNER WITH NIH AND OTHERS
ON BECAUSE WE'RE EMBARKING ON
CATALYTIC WORK IN THE
NEUROETHICS TRAINING AREA, AND
THAT'S BEING DONE THROUGH A FEW
DIFFERENT PROGRAMS.
ONE OF THE SIGNATURE PROGRAMS IS
UNDER NEXT GEN PILLAR, AND WE'RE
LAUNCHING DANA CENTERS IN
NEUROSCIENCE AND SOCIETY, WHERE
ONE OF THE KEY GOALS IS
PROVIDING BOTH NEUROETHICS
EDUCATION AND NEUROETHICS
TRAINING.
AND SO IT'S A CATALYTIC EFFORT
THOUGH.
WE HOPE WE CAN PARTNER WITH
OTHERS WHO CAN TAKE UP THE
FRUITS OF THOSE CATALYTIC
OUTCOMES AND FIND PATHWAYS FOR
SUSTAINED FUNDING IN THE FUTURE.
AND ANOTHER RELEVANT INITIATIVE
IS THAT WE'RE SETTING UP A DANA
NEUROSCIENCE IN SOCIETY CAREER
TRAINING NETWORK, SO ALSO
PROVIDING PATHWAYS FOR THESE
TRAINEES TO CONNECT WITH EACH
OTHER, THESE COULD BE TRAINEES
THAT HAVE INTEREST IN
INTERSECTION OF NEUROSCIENCE AND
LAW, ETHICS, HUMANITIES AND SO
ON, TO CONNECT WITH EACH OTHER
AND ALSO THINK ABOUT DIFFERENT
PATHWAYS THAT COULD BE BUILT OUT
IN THE FUTURE.
SO THANK YOU SO MUCH FOR THAT
QUESTION, TED.
THANK YOU FOR THE INVITATION TO
SHARE, JOHN.
>>GREAT OPPORTUNITIES.
WE'RE REALLY LOOKING FORWARD TO
SEEING HOW THESE PROGRAMS
DEVELOP.
>>ANY OTHER QUESTIONS OR
COMMENTS FOR CHRISTINE OR NEWG
MEMBERS?
OKAY.
THANK YOU AGAIN, CHRISTINE.
>>THANK YOU THANK YOU VERY MU.
THANKS FOR YOUR ATTENTION.
>>JOHN IS GOING TO INTRODUCE
JOHN.
JOHN, DO YOU HAVE YOUR SLIDES
READY?
>>I DO.
>>I'M DELIGHTED TO INTRODUCE
JOHN MAUNSELL, PROFESSOR OF
NEUROBIOLOGY, RECEIVED HIS
BACHELOR'S DEGREE FROM DUKE
UNIVERSITY, Ph.D. FROM CAL
TECH, WE'RE BOTH TECHERS, I
GUESS, BEFORE PURSUING POSTDOC
STUDIES AT M.I.T., HIS LAB
STUDIES VISUAL STIMULI IN THE
BRAIN AND ACTIVITY IN NEURONS
UNDERPIN CERTAIN BEHAVIORS,
CONTRIBUTIONS RECOGNIZED BY MANY
HONORS, THESE INCLUDE ELECTION
TO AMERICAN ASSOCIATION FOR
ADVANCEMENT OF SCIENCE IN 2002,
AMERICAN ACADEMY OF ARTS AND
SCIENCES IN 2014, NATIONAL
ACADEMY OF SCIENCES IN 2021.
IN ADDITION TO SERVING ON THE
NATIONAL ADVISORY COUNCIL FOR
NINDS, BRAIN MCWG, PROVIDED
SERVICE TO COMMUNITY, EDITOR IN
CHIEF OF NEUROSCIENCE 2007 TO
2014.
WE CAN'T THANK YOU ENOUGH FOR
THAT, SINCE 2021 EDITOR OF
ANNUAL REVIEW OF VISION SCIENCE.
JOHN ALSO VERY NOTABLY
CO-CHAIRED THE BRAIN 2.0 WORKING
GROUP, REPORT ISSUED IN 2019,
CONTINUES TO GUIDE EFFORTS IN
ACCELERATING DISCOVERIES TO
CURES OF HUMAN BRAIN DISORDERS
AND BRAIN INITIATIVE.
THE TITLE IS THE ROLE OF THE
LOCUS COERULEUS IN VISUAL
SPATIAL ATTENTION.
SO ALL YOURS.
>>THANK YOU.
CAN YOU HEAR ME.
>>YEAH.
>>THANKS FOR THE KIND
INTRODUCTION AND INVITATION TO
TELL YOU ABOUT OUR WORK HERE
TODAY.
MY LAB HAS LONG BEEN INVOLVED IN
STUDYING THE NEURAL CORRELATES,
MOSTLY HOW SENSORY NEURONS IN
VISUAL CORTEX OF MONKEYS CHANGE
RESPONSES DEPENDING ON WHETHER
AN ANIMAL PAYS ATTENTION TO OR
IGNORES A STIMULUS IN RECEPTIVE
FIELD.
I WANT TO TELL BUT STUDIES IN
THE BRAINSTEM LOOKING AT A NEW
STRUCTURE FOR US, LOCUS
COERULEUS, AND I'LL TELL YOU
WHAT WE FOUND ABOUT HOW MUCH
IT'S CONTRIBUTING TO VISUAL
SPATIAL ATTENTION.
I WANT TO GIVE AN OVERVIEW ABOUT
WHY WE STUDY ATTENTION AND TYPES
OF APPROACHES THAT WE USE.
WE KNOW A LESS ABOUT COGNITIVE
FUNCTION, IMPORTANT TO
UNDERSTAND NEURAL UNDERPINNINGS
OF COGNITIVE FUNCTION, AMONG THE
VARIOUS COGNITIVE FUNCTIONS WE
HAVE AVAILABLE, ATTENTION TURNS
OUT TO BE ONE RELATIVELY EASY TO
CONTROL AND QUANTIFY COMPARED TO
OTHERS LIKE DECISION MAKING OR
MEMORY.
IN FACT WE USE TECHNIQUES TO GO
BACK TO METHODS DEVELOPED IN THE
1960s BY PSYCHOLOGISTS.
MOST INVOLVE ASKING SUBJECT,
HUMANS OR MONKEYS, HOLD THEIR
GAZE ON FIXATION SPOT SO
STIMULUS IS THE SAME FROM TRIAL
TO TRIAL, PAY ATTENTION TO THE
PERIPHERY, A SMALL CHANGE.
COULD BE ANYTHING, SPEED OR
ORIENTATION, THAT DOESN'T MATTER
SO MUCH.
BUT WHAT WE DO IS GIVE THE
SUBJECTS INFORMATION ABOUT WHERE
THE CHANGE IS LIKELY TO HAPPEN.
IT'S ALWAYS ON ONE SIDE OR THE
OTHER.
WE CAN CUE THEM IT'S MORE LIKELY
TO OCCUR ON ONE SIDE.
WHEN WE LOOK AT PERFORMANCE THY
ARE MORE SENSITIVE TO SMALLER
CHANGES, RELATIVE TO THE
SITUATION WHERE WE GIVE AN
INVALID CUE.
IN FACT THE CHANGE OCCURS WHERE
THEY ARE NOT EXPECTING IT.
THIS IS ESSENTIALLY THE
DEFINITION THAT WE'RE USING FOR
VISUAL SPATIAL ATTENTION.
THIS MEANS UNDER SOME CONDITIONS
WHEN SUBJECTS ARE WORKING
THRESHOLD AT GIVEN SENSORY
STIMULUS MIGHT BE VERY POOR
PERFORMANCE WITHOUT ATTENTION
BUT ADDING ATTENTION MAKES THAT
PERFORMANCE MUCH BETTER.
AND I'LL JUST SUMMARIZE DECADES
OF WORK FROM OUR LAB AND OTHERS
IN TERMS OF WHAT GOES ON IN
SENSORY NEURONS WHEN YOU MAKE
THESE CHANGES, AND ONE OF THE
BIG ONES IS THAT BASICALLY THE
NEURONAL SIGNALS GET STRONGER,
WHEN AN ANIMAL IS PAYING
ATTENTION TO STIMULUS OF THE
NEURON RECEPTOR, INSIDE RECEPTOR
FIELD, THAT NEURON WILL
TYPICALLY FIRE MORE SPIKES IN
THE RESPONSE TO THE STIMULUS.
THESE ARE JUST DATA SUMMARIZING
RESPONSES FROM HUNDREDS OF CELLS
ACTUALLY IN MONKEY VISUAL
CORTEX, AREA BEFORE, THIS IS,
PARDON ME, THIS SEEMS TO BE
PRESENTED TWICE, ONCE WHEN THE
ANIMAL NOT PAYING PHYSICIAN IN
BLUE, AND ONE WHEN PAYING
ATTENTION, 30% INCREASE IN
STRENGTH OF RESPONSE OVERALL.
THAT'S QUITE TYPICAL.
EARLIER STAGES IN VISUAL CORTEX
HAVE SMALLER CHANGES, LATER
STAGES HAVE LARGER CHANGES BUT
YOU'LL TYPICALLY SEE A STRONGER
RESPONSE.
AND THIS IS VERY MUCH LIKES WHAT
HAPPENS WHEN YOU INCREASE
INTENSITY OF THE STIMULUS.
AND PERCEPTION ATTENTION HAS
THAT EFFECT, STIMULUS IS MORE
PROMINENT.
MORE SIGNAL IS GOOD, WOULDN'T
HELP IF MORE NOISE WENT ALONG
BUT ATTENTION DOES NOT INCREASE
THE NOISE.
IN FACT THE NOISINESS RESPONSE
IS DECREASED WITH ATTENTION,
JUST SLIGHTLY.
I'M REFERRING TO THE FACT IF YOU
PRESENT THE SAME STIMULUS OVER
AND OVER NEURONS GIVE SOMEWHAT
VARIABLE RESPONSES, THESE ARE
ALL RESPONSES FROM ONE NEURON TO
MANY REPETITIONS OF THE
STIMULUS, EACH LINE IS ONE
REPETITION, EACH TICK MARK IS
ACTION POTENTIAL.
CELL RESPONDED ON TRIAL BUT
NUMBER OF SPIKES ARE
CONSIDERABLY, IF YOU COUNT THEM
YOU MIGHT GET FIVE PER STIMULUS
PRESENTATION UP TO 20 SPIKES PER
STIMULUS PRESENTATION.
THAT VARIANCE LIMITS RELIABILITY
OF THE CELLS, THE FACT IS
ATTENTION IS TYPICALLY FOUND TO
REDUCE THAT VARIANCE A BIT.
IT'S NOT A BIG EFFECT, AS I
MENTIONED, BUT IN HAND WITH
LARGER SIGNAL MEANS SIGNAL TO
NOISE OF MOST SENSORY NEURONS IN
CORTEX IS IMPROVED WHEN
ATTENTION IS DIRECTED TO THAT
STIMULUS.
THE LAST MEMBER OF THE TRIAD IS
MORE COMPLICATED.
IT'S THAT NEIGHBORING CELLS HAVE
VARIANCE IN RESPONSE, TENDS TO
BE CORRELATED.
SO CELLS HAVE A WEAK
CORRELATION, CORRELATION
COEFFICIENT ABOUT 0.1 IN SPIKE
COUNTS, HAS IMPACT FOR AMOUNT OF
INFORMATION IN THE POPULATION.
THE MORE CELLS ARE CORRELATED
LESS INFORMATION YOU CAN GET
FROM THE POPULATION BECAUSE THEY
SEND TO BE SAYING THE SAME
THING.
ATTENTION ACTS TO REDUCE THAT
CORRELATION, MAYBE THE MOST
IMPORTANT THING ATTENTION IS
DURING FOR NEURONAL
REPRESENTATION, BY REDUCING THAT
CORRELATION IT ENHANCES THE
AMOUNT OF INFORMATION IN THE
POPULATION, ABOUT THE STIMULUS
THAT WE'RE CONSIDERING.
SO THESE THREE EFFECTS GO HAND
IN HAND WITH VISUAL SPATIAL
ATTENTION AND ARE THOUGHT TO
PROVIDE BETTER SIGNAL
REPRESENTATION -- STIMULUS
REPRESENTATION THAT ALLOWS FOR
BETTER PERFORMANCE.
THESE HAVE BEEN SEEN WIDELY IN
VISUAL CORTEX, BUT THE ORIGINS
ARE NOT WELL UNDERSTOOD, A LOT
OF REGIONS ARE THOUGHT TO
CONTRIBUTE TO THIS IN PRE-FRONT
CORTEX.
TODAY I WANT TO FOCUS ON A
BRAINSTEM STRUCTURE WE FOUND
MAKES SUBSTANTIAL CONTRIBUTION
TO THE SIGNALS WE'RE SEEING IN
CORTEX.
THIS IS THE LOCUS COERULEUS.
IT'S A SMALL STRUCTURE, EACH OF
US HAS ABOUT 50,000 NEURONS IN
OUR LOCUS COERULEUS.
THAT SOUNDS LIKE A LOT BUT IN
FACT IT'S A FEW MILLIMETERS
ACROSS.
IT'S SMALL IN SIZE BUT HAS A
WIDE REACH, SENDS PROJECTIONS TO
ALL OF THE NEOCORTEX, CEREBELLAR
CORTEX AND OTHER STRUCTURES, A
LOT OF REACH, INVOLVED IN
AROUSAL.
WE WANTED TO SEE HOW MUCH IT
MIGHT BE INVOLVED IN SELECTIVE
ATTENTION, NOT SOMETHING THAT
IT'S USUALLY ASSOCIATED WITH.
AND HERE I HAVE TO SAY ALL OF
THIS WORK WAS PILOTED AND TAKEN
CHARGE OF BY A VERY SMART
POSTDOC WHO CAME TO THE LAB FOR
NEUROMODULATORY SYSTEMS
RECOGNIZING AROUSAL FUNCTION
MIGHT BE RELEVANT FOR SELECTIVE
ATTENTION BECAUSE NOBODY HAD
ACTUALLY LOOKED AT HOW IT
BEHAVES IN TASKS I'VE DESCRIBED
WE'RE USING IN THE CORTEX.
SUPRIYA ALSO RECOGNIZED THE
LOCUS COERULEUS WAS A CHOICE
TARGET FOR OPTOGENETIC
MANIPULATIONS, HE WAS CORRECT
AND I'LL SHOW YOU DATA
MANIPULATING LOCUS COERULEUS
ACTIVITY WITH OPTOGENETICS.
THE TASK WAS AS DESCRIBED,
ANIMALS FIXATED ON A SPOT IN
EACH TRIAL, AFTER FIXATION WAS
GOOD, TWO SAMPLES, PATTERNS ON
EITHER SIDE, THEY DISAPPEARED.
AND THEN AFTER A SHORT DELAY, A
TEST STIMULUS APPEARED, ON THE
LEFT SIDE OR THE RIGHT SIDE.
AND WHETHER THE TEST STIMULUS
HAD THE SAME ORIENTATION AS
SAMPLE STIMULUS THAT HAD
APPEARED ON THAT SIDE.
HALF THE TIME IT DID.
AND THAT WAS A MATCHED STIMULUS.
THE TARGET CAME UP LATER, HALF
THE TIME IT DIDN'T.
IT WAS ROTATED, THE ANIMAL HAD
TO MAKE THE TARGET THAT CAME UP
LATER.
THIS WAS AN ATTENTION TASK,
DIRECTING ATTENTION TO ONE SIDE
OR THE OTHER BY USING BLOCKS OF
TRIALS WHERE MOST OF THE
STIMULI, TESTS THAT CAME UP,
WERE ON THE LEFT, MOST ON THE
RIGHT, CAUSING ANIMALS TO DIRECT
ATTENTION AS YOU MIGHT HOPE, SO
WE COULD LOOK AT HOW CHANGING
THE ANIMAL'S ATTENTION FROM ONE
SIDE OF THE VISUAL FIELD TO THE
OTHER AFFECTED RESPONSES WE SAW
IN THE LOCUS COERULEUS.
THE BEHAVIOR WAS GOOD, THE
ANIMALS DID PAY ATTENTION.
THIS IS DONE IN TWO ANIMALS,
MONKEY 1 ON TOP, MONKEY 2 ON
BOTTOM.
WE ASKED THEM TO PAY ATTENTION
TO THE CONTRALATERAL SIDE
OPPOSITE WHERE WE WERE
RECORDING, OR IPSILATERAL SIDE,
THERE WAS A NICE IMPROVEMENT AS
CHANGES GOT BIGGER SO THE ANIMAL
WAS TRYING TO SELECT
ORIENTATIONS WHEN SMALL,
PERFORMANCE NOT I HAVE GOOD,
MEASURED THE PRIME FUNCTION
SIGNAL DETECTION THEORY, ZERO IS
CHANCE, ABOVE 2 OR 3 IS THE
RANGE OF 90% CORRECT.
THEY QUICKLY DID WELL IN
SATURATED AT 30 DEGREES CHANGES.
IF IT APPEARED ON THE SIDE NOT
EXPECTED PERFORMANCE WAS WORSE,
EVIDENCE IT WAS PAYING MORE
ATTENTION ON ONE SIDE THAN ON
THE OTHER.
REGARDLESS OF WHETHER WE ASK
THEM TO ATTEND TO LEFT OR RIGHT,
IN BOTH ANIMALS, MONKEY 2 NOT
ATTENDING AS HARD, SAME EFFECT
IN BOTH.
ANIMALS DOING BEHAVIORAL TASKS,
WE COULD RECORD FROM THE LOCUS
COERULEUS AS THEY DID THIS TASK.
WE SAW A DIFFERENCE IN RESPONSES
DEPENDING WHICH SIDE WAS
VISUALLY DISPLAYED.
CELLS DID NOT SPIKE STRONGLY,
RATES OF ZERO TO 10 SPIKES PER
SECOND, YOU CAN SEE A DIFFERENT
IN THE RESPONSE OF THIS NEURON
DEPENDING ON WHETHER THE ANIMAL
WAS PAYING ATTENTION TO
CONTRALATERAL STIMULUS, THE SIDE
WE WERE RECORDING OR IPSILATERAL
SIDE, ALMOST ALL OR NONE.
BOTH STIMULI PRESENT IN BOTH
CASE, SOMETIME ZERO, WHICH ONE
IS THE ANIMAL PAYING ATTENTION
TO.
THESE PLOTS SUMMARIZE OVERALL
EFFECT.
MONKEY 2 A RISE IN RESPONSE WHEN
ANIMAL IS PAYING ATTENTION TO
IPSILATERAL SIDE, 5 TO 1
DIFFERENCE DEPENDING WHICH SIDE
THE ANIMAL IS PAYING ATTENTION
TO.
THE MONKEY 1 EVEN A BIT OF
SUPPRESSION WHEN THE ANIMAL IS
PAYING ATTENTION TO THE
IPSILATERAL SIDE.
THIS MODULATION, THIS SCALE IS
MUCH LARGER THAN WE EVER SEE IN
CORTEX.
I MENTIONED A 30% MODULATION,
THAT'S DIFFICULT.
ALL MODULATIONS ARE DRAMATIC.
THE IMPLICATION IS THE LOCUS
COERULEUS WITH ITS PROJECTIONS
IS IN FACT ACTUALLY DOING
SOMETHING SELECTIVE HERE.
THIS IS NOT JUST AROUSAL SIGNAL.
THE ANIMAL IS WORKING IN ALL
THESE CASES.
IT'S WHETHER OR NOT THE ANIMAL
IS PAYING ATTENTION TO STIMULI
CONTRALATERAL OR IPSILATERAL TO
THE LOCUS COERULEUS,
CONTRIBUTING TO MODELS IN THE
CORTEX.
IT SEEMS TO BE TIED TO THE
ANIMAL'S SUCCESS USING SIMILAR
PLOTS.
WHEN THE ANIMAL IS ATTENDING TO
CONTRALATERAL STIMULUS SORTING
OUT WHETHER THE BE A MAL --
ANIMAL GOT IT CORRECT OR NOT.
THESE ARE THE CORRECT TRIALS,
WHEN WE ASKED THE ANIMAL TO
ATTEND TO THE CONTRALATERAL SIE
HE GETS IT WRONG WE DON'T SEE
MODULATION, CLEAR INDICATION THE
CELLS ARE CONTRIBUTING IN A
SUBSTANTIAL WAY TO THE ANIMAL'S
ATTENTION TO THAT SIDE.
TO DEMONSTRATE THOUGH, USING
OPTOGENETICS TO PERTURB THE
ACTIVITY OF THE CELLS.
THE REASON, ONE OF THE REASONS
SO INTERESTED IN THIS STRUCTURE,
CHOICE TARGET FOR OPTOGENETIC,
CELLS ARE NORADRENERGIC, THE
ONLY ONES IN THAT AREA, POSSIBLE
TO FLOOD THAT REGION WITH VIRUS
AN ONLY GET EXPRESSION IN
NORADRENERGIC CELLS.
A VIRUS WAS USING NORADRENERGIC
TO GET CELLS TO EXPRESS CRE AND
ANOTHER THAT USED PRE-EXPRESSING
CELLS TO EXPRESS
CHANNELRHODOPSIN.
IT DID A GOOD JOB GETTING
RELATIVELY COMPLETE EXPRESSION
IN THESE LOCUS COERULEUS CELLS
WITHOUT GETTING EXPRESSION IN
ANY NORADRENERGIC CELLS, ACTUAL
TO ACTIVATE THESE CELLS WHILE
THE ANIMAL IS DOING THE TASK TO
SEE EFFECT ON BEHAVIORAL
PERFORMANCE.
THE EXPRESSION IS GOOD.
AND IT CAUSED GOOD SPIKING.
IF WE CHANNELED A LASER ON THE
LOCUS COERULEUS WE GET SPIKES OR
BREAKS COMPLEMENTING THE SPIKES
FROM STIMULI AND COULD ADJUST
THE RATE TO GET GREATER OR
LESSER SPIKING.
WE PUT IN A MODERATE LEVEL OF
ACTIVATION IN THE LOCUS
COERULEUS, WHAT WE SAW WAS A
PRETTY DRAMATIC INCREASE IN
BEHAVIOR PERFORMANCE OF THE
ANIMAL.
WHEN WE ASKED THE ANIMAL TO
ATTEND TO CONTRALATERAL SIDE AND
WORK WITH THE SIGNAL THERE THE
CASE WHERE IS WE ACTIVATED THE
LOCUS COERULEUS USING
CHANNELRHODOPSIN CAUSED A
SUBSTANTIAL IMPROVEMENT IN
PERFORMANCE ACROSS THE BOARD,
WITH WEAKER STIMULI ANIMAL DID
BETTER.
THIS IS TRUE FOR BOTH ANIMALS.
IF ON THE OTHER HAND WE
STIMULATED WHILE ANIMAL WAS
PAYING ATTENTION TO IPSILATERAL
SIDE IT WAS LESS PERFORMANCE AS
IF ACTIVATING MORE ATTENTION ON
THE CONTRALATERAL SIDE IMPAIRED
THE PERFORMANCE ON THE
IPSILATERAL SIDE, SUBSTANTIAL
CHANGES IN PERFORMANCE BASED ON
ACTIVATING ONE SMALL STRUCTURE.
THE LAST THING I WANTED TO SHOW
YOU WE WERE INTERESTED IN
GETTING SOME INDICATION OF HOW
RAPIDLY THE LOCUS COERULEUS
PREDICTED HERE.
WE WERE PRESENTING ACTIVATION TO
THE LOCUS COERULEUS AROUND THE
TIME THE SAMPLE STIMULUS WAS
PRESENTED.
A 400 MILLISECOND PERIOD
STARTING SLIGHTLY BEFORE,
LASTING THROUGH THE
PRESENTATION, THOUGHT IT WOULD
BE A GOOD TIME TO TEST BUT
DIDN'T KNOW WHETHER THE WHOLE
PERIOD WAS NEEDED OR NOT.
WE WANTED TO LOOK AT SMALLER
INTERVALS.
TURNS OUT IT'S VERY DIFFICULT TO
USE VERY SHORT PULSES TO PROBE
BEHAVIOR.
YOU CAN GET NO EFFECT AT ALL OR
TURN THE POWER UP ENOUGH TO GET
EFFECT YOU SEND CIRCUITS THAT GO
ON TO MAKE IT DIFFICULT TO
ACTUALLY PICK OUT WHICH SPECIFIC
TIME TO ACTIVITY OR NOT.
SO WHAT WE DID WAS USED A
TECHNIQUE DEVELOPED FOR
OPTOGENETIC STIMULATION IN MICE,
WHITE NOISE REVERSE CORRELATION
METHOD, VERY EFFECTIVE FOR
SMALLER INTERVALS.
I WANT TO SPEND A COUPLE MINUTES
DESCRIBING THAT APPROACH.
THIS REVERSE CORRELATION
TECHNIQUE HAS BEEN WIDELY USED
TO STUDY SENSORY RECEPTOR
FIELDS, VISUAL NEURONS, OTHER
SENSORY SYSTEMS AS WELL.
AND YOU MAY BE FAMILIAR WITH IT,
THAT APPROACH.
THIS SLIDE SCHEMATIZES HOW YOU
CAN USE A NOISE STIMULUS TO PLOT
FIELDS IN THE VISUAL SYSTEM.
THE IDEA IS SIMPLE ENOUGH, YOU
JUST RAPIDLY PRESENT A SERIES OF
DIFFERENT NOISE STIMULI, NOISE
HERE IS CHECKERBOARD WITH EVERY
PIXEL MONKEY WHITE OR MONKEY
BLACK, CHANGING MAYBE TEN TIMES
A SECOND, SIMPLY PRESENTED FOR
MANY MINUTES ON END.
EVERY SPIKE IS RECORDED.
FOR EACH SPIKE THEN THE STIMULI
THAT OCCURRED IMMEDIATELY
BEFORE, TWO OR THREE STEPS
BEFORE, ARE RECORDED.
THAT CORRECTED FOR EVERY SPIKE
SO YOU START LOOKING AT WHAT THE
NOISE STIMULI WERE AROUND THE
TIME OF SPIKING.
AND THEN IN THE ANALYSIS AFTER
YOU'VE GOTTEN MAYBE 10,000
SPIKES YOU CAN AVERAGE THESE
NOISE STIMULI AND ASK WHAT WAS
THE AVERAGE STIMULUS PRESENT,
BEFORE THE SPIKE OCCURRED OFF
BEFORE THAT.
AND IN MOST CASES SCORED QUITE
WELL, IN MOST CASES SPIKES
OCCURRED WHEN, SAY, THERE WAS A
BRIGHT STIMULUS IN THE RECEPTOR
FIELD, SO WHEN YOU HAVE ON
AVERAGE MORE LUMINANCE IN THE
REGION, YOU GET A SPIKE, BACK N
TIME IT WILL FADE AWAY WITH
TIME.
AND YOU CAN MAP OUT A SPATIAL
AND TEMPORAL RECEPTOR FIELD
GIVING YOU STRENGTH OF RESPONSE
IN SPACE AND ALSO ACROSS TIME,
HOW IT DIMINISHES ACROSS THESE.
AND I'LL JUST SAY THE APPROACH
IT MAKES IN TWO WAYS IS VERY
EFFICIENT.
A LOT OF INFORMATION QUICKLY,
AND ALLOWS YOU TO USE WEAK
STIMULUS, YOU DON'T HAVE TO HIT
THE CIRCUIT HARD, YOU CAN WORK
IN THE NATURAL FOR THE CIRCUIT.
BEING USED WIDELY TO UNDERSTAND
HOW VISUAL STIMULI RELATE TO
RESPONSES BUT I'LL POINT OUT
THIS APPROACH HAS BEEN USED
DIRECTLY FROM VISUAL STIMULI TO
BEHAVIOR, THE APPROACH IS
PERFECTLY ANALOGOUS, THIS IS A
STUDY, NATIONAL EYE INSTITUTE,
THEY ASKED MONKEYS IN THIS CASE
TO VIEW A VERY RAPIDLY CHANGING
3D DISPLAY, USING 3D GLASSES TO
SEE THE STIMULUS.
IT CHANGED EVERY 10
MILLISECONDS, MORE NEAR OR FAR,
COULD DO THE TASK, PERFORMED
QUITE WELL.
BY USING THIS VARIED STIMULUS
OVER MANY TRIALS THEY COULD
ACTUALLY SORT OF DO REVERSE
CORRELATION AND LOOK AT THE
DIFFERENCE TO SEE BASICALLY HOW
MUCH WEIGHT ON STIMULI EARLY IN
THE TRIAL VERSUS LATE IN THE
TRIAL.
IDEAL PERFORMANCE WOULD WEIGHT,
EVERY POINT IS EQUALLY
INFORMATIVE BUT MONKEYS LIKE
PEOPLE DON'T DO THAT.
THEY PUT MORE WEIGHT EARLY IN
THE TRIAL, STIMULUS FIRST
APPEARS, DIMINISHES TO VERY
LITTLE WEIGHT TO THE STIMULI
THAT APPEARED IN THE END.
SO YOU CAN PULL OUT A STIMULUS
BEHAVIOR THIS WAY.
WHAT WE DID, WE WANTED TO DO,
WAS ACTUALLY RELATE NEURONAL
SPIKING TO BEHAVIOR IN THIS WAY.
WE WERE USING A NOISE
OPTOGENETIC STIMULUS OF LOCUS
COERULEUS TO SEE HOW THAT WOULD
AFFECT BEHAVIOR, A TEMPORAL
KERNEL OF WHERE IN THE TRIAL
THIS OPTICAL SIGNAL IS AFFECTING
BEHAVIOR AND THE DESIGN WAS
QUITE SIMPLE.
AS SOON AS THE ANIMAL FIXATED A
NOISE STIMULUS WAS DELIVERED TO
THE LOCUS COERULEUS.
IT SPANNED THE FULL PERIOD
ALLOWING SAMPLE STIMULUS, THEN
THE ANIMAL DID THE TASK.
IF IT HAD THE NOISE STIMULI
EFFECT, NOISE CORRELATION A
SUCCESSFUL AND FAILED TRIALS,
LOOKING AT THE DIFFERENCE.
IT WORKED QUITE EFFECTIVELY FOR
THE LOCUS COERULEUS.
WE FOUND IN BOTH ANIMALS THERE
WAS A PERIOD ABOUT 80
MILLISECONDS PRIOR TO THE ONSET
OF THE SAMPLE STIMULUS WHEN
SPIKING IN THE LOCUS COERULEUS
HAD HAD AN EFFECT.
RISE ON THE BLUE CURVES WHEN THE
ANIMAL WAS DOING CONTRALATERAL
DETECTION OF ORIENTATION CHANGE,
INCREASING THE ACTIVATION OF THE
LOCUS COERULEUS INCREASED
ANIMAL'S CHANCE OF SUCCESS,
SIMILAR PROFILE IN BOTH CASES,
OCCURRED BEFORE THE SAMPLE
STIMULUS, WE THINK THAT MADE
SENSE BECAUSE IT TAKES TIME FOR
A SPIKE IN THE LOCUS COERULEUS
TO TRAVEL ALL THE WAY UP THE
CEREBRAL CORTEX, DELIVER
NEUROMODULATORY SIGNALS THAT
CHANGE THE STATE OF NEURONS IN
VISUAL CORTEX IN TIME FOR THE
VISUAL STIMULUS TO ARRIVE SO YOU
THINK THIS ACTUALLY MAKES SOME
SENSE, OBVIOUSLY WE NEED TO DO
MORE ON THIS.
I WOULD ALSO POINT OUT THERE'S
ANOTHER MESSAGE IN THESE KERNELS
HERE.
THIS IS THE SPIKING HERE
MATTERS, BUT WE WERE DELIVERING
STIMULATION THROUGHOUT THIS
PERIOD, INCREASING AND
DECREASING SPIKING ON DIFFERENT
TRIALS, THE FLATNESS OF THE
LINES IN THIS REGION STAYING
INSIDE 95% CONFIDENCE INTERVALS
LATER OR EARLIER SPIKES DON'T
MATTER ON PERFORMANCE OF THIS
TASK, WE THINK IT'S A NARROW AND
SPECIFIC TIME THAT AFFECTS THE
ANIMAL'S PERFORMANCE.
I THOUGHT OF THE LOCUS COERULEUS
ASSOCIATED WITH AROUSAL, INSTEAD
IT LOOKS SELECTIVE, AT LEAST AT
CONTRALATERAL LEVEL.
THE DYNAMICS OF THE LOCUS
COERULEUS ARE JUST AS FAST AS
ANYWHERE ELSE IN THE NERVOUS
SYSTEM.
SUMMARIZE, WE THINK THE LOCUS
COERULEUS IS PLAYING AN
IMPORTANT ROLE IN VISUAL SPATIAL
ATTENTION.
WE SHOWED SPECIFICITY BUT NEED
TO KNOW HOW SPECIFIC.
WE CAN PUT BOTH IN ONE
HEMISPHERE, AND SEE HOW
SPECIALIZED THEY ARE IN TERMS OF
VISUAL SPATIAL LOCATIONS.
ALSO THERE'S A QUESTION IS IT
NOT INVOLVED IN OTHER SENSORY
MODALITIES OR IF VISUAL FEATURES
AS WELL, THESE NEED TO BE
EXAMINED, THE LOCUS COERULEUS
MIGHT DO LOTS OF THINGS THERE.
AND WE NEED TO EXPLORE THE
RESOLUTION OF THESE INPUTS IN
THE CORTEX, HOW WIDELY EACH
NEURON'S TERMINATIONS EXTEND IN
CORTEX AND MIGHT BE INTERACTIONS
WITH ONGOING OTHER TRANSMITTER
SYSTEMS LIKE CHOLINERGIC RAISE
THE POSSIBILITY THAT CONDITIONS
OF TRANSMITTERS MIGHT MAKE THIS
A LOCALIZED SYSTEM WHEN WORKING
IN CONJUNCTION WITH INPUTS.
SO IT LOOKS LIKE THERE'S A LOT
UNDERSTOOD ABOUT THE LOCUS
COERULEUS, I TAKE IT AS A WAKEUP
CALL FOR ME IN TERMS OF
UNDERSTANDING BRAINSTEMS
CONTRIBUTING IN A SUBSTANTIAL
WAY TO THESE PROCESSES THAT WE
HAVE BEEN STUDYING.
IN CLOSING I'D LIKE TO
ACKNOWLEDGE THE MEMBERS OF THE
LAB THAT CONTRIBUTED OVER THE
YEARS TO THESE.
S,PRIYA AND JULIAN.
THANK YOU FOR YOUR ATTENTION.
>>THANKS, JOHN.
GREAT STUFF.
SO, IF FOLKS HAVE QUESTIONS, YOU
CAN RAISE YOUR HAND.
I SEE A QUESTION FROM JOSH IN
THE CHAT.
JOSH, DO YOU WANT TO READ IT OR
DO YOU WANT ME TO READ IT?
YOUR CHOICE.
I HAVE A QUESTION RELATED.
>>I CAN READ IT.
JOHN, YOU SORT OF ANSWERED IT
ALREADY.
REALLY FASCINATING.
WHAT'S THE -- WHAT DO YOU THINK
THE LIKELIHOOD SPECIAL
SELECTIVITY GOES BEYOND
CONTRALATERAL VERSUS
IPSILATERAL.
IT'S HARDER TO IMAGINE HOW YOU
GET SPECIFIC SPATIAL
SELECTIVITY.
>>YEAH, I THINK THAT'S THE
QUESTION.
I HAVE TO SAY I'M A BIT OF A
CONVERT NOW THAT I'VE SEEN SOME
SELECTIVITY.
I REALLY THINK IT'S LIKELY THERE
WILL BE MUCH MORE THERE.
I DON'T THINK THESE ARE 50,000
CELLS ALL WORKING IN LOCK-STEP.
AND SO IT'S SUCH A
STRAIGHTFORWARD QUESTION, SUCH A
MANAGEABLE EXPERIMENT, BRINGING
STIMULI TOGETHER, CLOSER AND
FARTHER APART GETTING SPATIAL
RECOGNITION.
I DON'T KNOW THE ANSWER BUT I'M
DYING TO FIND OUT.
>>IN RELATED QUESTION, I THINK
YOU TOUCH ON THIS, IN TERMS OF
WHETHER AND HOW THIS MIGHT
INFLUENCE OTHER SENSORY
MODALITIES, IN THE CASE OF
OLFACTION WE'RE NOT IN THE
NEOCORTEX, IT'S KIND OF ARGUABLE
THERE SPECIAL INFORMATION IS
ENCODED BEYOND MOVING A HEAD
AROUND, WHAT WOULD YOU PREDICT
MIGHT BE GOING ON THERE?
>>WE STUDY SPATIAL ATTENTION
BECAUSE IT'S TRACTABLE, WE STUDY
FEATURE ATTENTION OFF AND O
EFFECTS WITH ATTENDING TO A
PARTICULAR COLOR OR ORIENTATION
OR DIRECTION ARE SIMILAR IN MANY
WAYS.
AND SO ATTENDING TO A PARTICULAR
ODOR AND NOT ANOTHER ODOR,
THAT'S BASICALLY THE SAME
PROCESS.
I WOULDN'T BE SURPRISED AT ALL
IF THERE ARE ANALOGOUS EFFECTS.
OLFACTION IS QUITE DIFFERENT
ANATOMICALLY SO I'M PREPARED FOR
ANYTHING THERE.
BUT I THINK IT'S AN OPEN
QUESTION.
>>IT'S WEIRD, YES.
A QUESTION FROM TODD AND THEN
TED.
>>YEAH, (INDISCERNIBLE)
EXCITING STUFF.
THE TIMING FINDING THAT YOU HAVE
WITH THE 80 MILLISECOND AND
ABOVE, THE INTENTIONAL BLINK,
YOU SEE THAT STIMULI COMING
RAPIDLY, A SECOND STIMULUS
COMING RIGHT AFTER A FIRST ONE
OFTEN FAILED TO BE DETECTED,
I'VE SEEN COMPUTATIONAL
ACCOUNTS, ATTRIBUTING TO
REFRACTORY PERIOD, LC NEURONS
THAT LIKE AFTER ONE FIRING THEY
HAVE A LITTLE BIT OF LAG BEFORE
FIRING AGAIN AND THAT MAY BE A
CAUSE OF THAT.
HAVE YOU THOUGHT ABOUT THAT WITH
REGARD TO YOUR DATA OR PLAN TO
LOOK AT THAT ISSUE AT ALL?
>>YEAH, SO WE HAVE DATA IN
TERMS OF THE SORT OF NEURONAL
BEHAVIORAL KERNELS THAT WE'VE
LOOKED AT BUT I WILL SAY MOST OF
THE WORK WE'VE DONE HAS BEEN IN
MICE DURING REACTION TIME TASKS,
AND EVERYWHERE WE HAVE LOOKED
THE KERNELS ARE ALWAYS QUITE
BRIEF.
AND I SHOULD PERHAPS MENTION
WE'RE CONSERVATIVE IN USING
LET'S SAY NOT CUTTING EDGE
CHANNELRHODOPSINS.
EVERYWHERE WE'VE LOOKED SO FAR
WE ALWAYS SEE VERY BRIEF
KERNELS.
THAT IS THE EFFECTS ARE VERY
SHORT-LIVED, 100 MILLISECONDS AT
THE OUTSIDE, WHETHER WE'RE
TALKING ABOUT MOUSE V1 OR LOCUS
COERULEUS OR CORTEX IN MICE, IT
ALWAYS LOOKS THE SAME.
WE HAVEN'T DONE MANY STRUCTURE
YET.
IT'S JUST I THINK AN OPEN
QUESTION ABOUT IF WE GO TO
DIFFERENT TASKS, USE DIFFERENT
DESIGNS, ANIMAL AS IT TO
INTEGRATE STIMULUS CAN WE SEE
MORE EFFECT OR IS IT SOMETHING
BIOPHYSICAL, MAYBE A REFRACTORY
PERIOD GOING ON, JUST DON'T
KNOW.
>>TED?
>>HI, JOHN.
THANKS FOR AN INTERESTING TALK.
A NEUROCHEMICAL QUESTION, IN
THAT YOU SORT OF THINK LOOKING
AT THE FIRING OF THE LC AND
FIGURE, OKAY, IT'S FIRING, IT'S
GOING TO RELEASE NOREPINEPHRINE
BUT THERE'S A COUPLE STUDIES IN
THE HIPPOCAMPUS TALKING ABOUT
DOPAMINE RELEASE FROM THOSE
NEURONS.
WHAT'S THE SIGNIFICANCE OF THAT?
AND IS THERE A POSSIBLE
REGULATION ON TOP OF THESE
NEURONS FIRING THAT IN OTHER
WORDS THERE MAY BE SOME
REGULATION ON WHAT THEY ACTUALLY
RELEASE THAT MIGHT BE LOCAL?
I'M MAKING THAT UP.
I DON'T KNOW.
>>WELL, TED, YOU CALLED ME OUT
ON THIS.
MY EXPERTISE ON THIS IS NOT THAT
GREAT, SOPHIA WAS HOLDING MY
HAND THROUGH ALL OF THIS.
AS FAR AS I'M CONCERNED, ALL OF
THAT IS POSSIBLE.
I JUST DON'T KNOW WHAT THE
LIMITATIONS MIGHT BE OR WHAT'S
THERE.
BASICALLY WHAT I SEE IS THAT IT
MAKES SOME SENSE THAT AN ANCIENT
BRAINSTEM STRUCTURE IS THERE
MEDIATING ATTENTION BECAUSE
BIRDS NEEDED ATTENTION
THROUGHOUT, ALL ANIMALS HAVE
NEEDED, OF VARIOUS SORTS.
IN TERMS OF EXACTLY WHICH
TRANSMITTER SYSTEMS,
INTERACTIONS, SPATIAL EXTENT,
THERE'S A NUMBER OF THINGS THAT
NEED TO BE WORKED OUT AND MANY
THINGS I NEED TO LEARN.
>>THANKS.
>>GREAT TALK, JOHN.
ENJOYED IT.
MY QUESTION IS WHETHER THERE'S
ALSO A TONIC EFFECT IN LC, WILL
YOU MEASURE ANY DIFFERENCES IN
ACTIVITY AS A FUNCTION OF THINGS
LIKE TASK ENGAGEMENT OR
MOTIVATION, IN OTHER WORDS DOES
AVERAGE LEVEL GO DOWN AT THE END
OF YOUR BLOCKS?
>>YEAH, GOOD QUESTION.
I DON'T KNOW THE ANSWER TO THAT.
WE MOSTLY FOCUS ON THE PERIODS
WHERE WE'VE GOT THE ANIMAL UNDER
BEHAVIORAL CONTROL.
WHAT YOU SAID IS CERTAINLY A
POSSIBILITY, PLUS TONIC EFFECTS
ARE NOT GOING TO BE EASILY
DETECTED USING REVERSE
CORRELATION APPROACH.
SO, WE'RE JUST SIMPLY NOT GOING
TO SEE THINGS THAT ARE JUST AT
THE DC LEVEL.
SO, IT'S A GOOD QUESTION.
I THINK WE COULD APPROACH IT BUT
WE HAVEN'T GOTTEN THE RECORDINGS
BETWEEN TRIALS AT THE MOMENT TO
LOOK AT THOSE SORTS OF THINGS.
>>THANKS.
>>WALTER MADE A COMMENT IN THE
CHAT.
DO YOU WANT TO BRING THAT UP?
>>WONDERING IF THERE'S UNIFORM
THEORY OF -- IN THE SYSTEM THAT
YOU WORKED AT, I WAS PULLED BY
THIS PAPER I SAW A WHILE AGO
ABOUT VARIOUS -- NOT ENTIRELY
SIMILAR, AUDITOR RESPONSES WHEN
YOU PUT IN COCHLEAR IMPLANTS AND
THE EFFECTS OF LOCUS COERULEUS
STIMULATION THERE, WHERE, YOU
KNOW, IT'S NOT -- IT DOESN'T
HAVE THAT TEMPORAL DATA THAT YOU
HAVE, BUT, YOU KNOW, BASICALLY
GETTING ALL THESE SIGNALS AND
THE LOCUS COERULEUS STIMULATION
IS REALLY CRITICAL AND
ORGANIZING THAT STIMULATION TO
INFORM BEHAVIOR.
I WAS WONDERING HAVE YOU THOUGHT
ABOUT WHAT YOU'VE BEEN AT, IS
THERE SOME KIND OF GENERAL --
ARE YOU ON TO SOME KIND OF
GENERAL MECHANISM IN THE NERVOUS
SYSTEM TO TUNE CIRCUITS?
A WHOLE BUNCH OF DIFFERENT
SENSORY STIMULI.
>>THANKS, WALTER.
I WOULD LIKE TO THINK SO.
YOU KNOW, SO WHEN WE STUDY
VISUAL SPATIAL VERSUS SPECIAL
FEATURE ATTENTION, EVERYTHING
LOOKS THE SAME.
I MEAN SOME THINGS ARE EASIER TO
CONTROL, SOMETIMES YOU GET
BIGGER EFFECTS BUT IN TERMS OF
THE TIMES OF NEUROPHYSIOLOGICAL
SIGNALS IT ALWAYS LOOKS THE
SAME.
AND WHAT I KNOW ABOUT AUDITORY
ATTENTION AND SOMATOSENSORY
ATTENTION, IT IS THE SAME STORY.
I LIKE TO THINK AT SOME LEVEL AT
LEAST CORTEX IS CORTEX AND ALL
THESE MECHANISMS WILL HAVE TIGHT
ANALOGIES IF NOT EQUIVALENT
CIRCUIT MECHANISMS.
SO I THINK THERE'S A GOOD CHANCE
FOR THAT.
AND IT WOULD BE MY HOPE THAT
THERE WOULD BE SOME CONSISTENCY
AT SOME LEVEL.
SO I THINK THAT COULD EASILY BE
THE CASE, WE'RE LOOKING AT
SOMETHING THAT'S WIDELY DEPLOYED
AND IT'S SIMILAR ACROSS
DIFFERENT SENSORY MODALITIES.
POTENTIALLY ACROSS COGNITIVE
MODALITY, RIGHT?
IMPROVING QUALITY OF THOUGHT,
FOR EXAMPLE.
>>HOW ABOUT -- I MEAN DO YOU
KNOW IF THE LOCUS COERULEUS
STIMULATION ACTUALLY ENABLES THE
MONKEYS TO DO BETTER A WEEK
LATER THAN THEY WOULD HAVE
OTHERWISE?
>>I DON'T KNOW THAT.
WE HAVEN'T LOOKED.
SO I REALLY JUST DON'T HAVE ANY
INFORMATION.
>>OKAY.
WE'RE ON TIME.
ANY OTHER QUESTIONS?
WE HAVE ANOTHER MINUTE BY MY
CLOCK.
THANKS, JOHN, FOR A TERRIFIC
TALK.
CLEARLY VERY STIMULATING AND
BASED ON THE DISCUSSION, THANK
YOU ALL FOR BEING HERE AND
ATTENDING, AND I'LL HAND IT BACK
TO KRISTIN TO WRAP US UP FOR THE
OPEN SESSION
>>THANK YOU.
THANK YOU, JOHN, FOR THE TALK.
BEAUTIFUL SET OF EXPERIMENTS.
SO HARD TO TARGET THOSE
BRAINSTEM AREAS.
THAT'S JUST FANTASTIC WORK.
AS WE KNOW, EXCITING SCIENCE
LEADS TO EVEN MORE EXCITING
QUESTIONS.
SO THANKS AGAIN.
I THINK THAT WILL WRAP US UP.
WE'RE GOING TO END ON TIME.
PERFECT TIMING TODAY.
SO THIS WILL CONCLUDE THE OPEN
SESSION OF OUR MCWG MEETING.
FOR OUR MEMBERS, AND GOVERNMENT
EMPLOYEES, WE'LL HAVE A
30-MINUTE BREAK AND THEN WE'LL
GET INTO THE CLOSED SESSION FOR
THE FUNDING PLANS.
SO THANK YOU ALL FOR YOUR
CONTRIBUTIONS TODAY AND YOUR
ATTENTION.
AND HAVE A GOOD BREAK, FOR THOSE
OF US.
AND EVERYONE ELSE, HAVE A GREAT
DAY.