>>WELCOME BACK.
YESTERDAY WE HAD TWO FANTASTIC
PLENARY LECTURES ONE FROM DIANA
BAUTISTA WITH THE IMMUNE
INTERACTIONS REMINDING US YES,
THE BRAIN INTERACT WITH STUFF IN
THE PERIPHERY AND THEN BETH
BUFFALO COVERED SPATIAL
NAVIGATION IN PRIMATES GIVING US
TANTALIZING CLUES AND WE HAD A
GREAT POSTER SESSION AND HAD
HIGH SCHOOL STUDENTS SUBMIT
ESSAYS ON THE ETHICAL
IMPLICATIONS OF NEURAL
TECHNOLOGY AND GRATIFYING TO SEE
THE NEXT GENERATION OF HOPEFULLY
SCIENTISTS CONSIDERING THE
ETHICAL IMPLICATIONS OF NOT ONLY
WHAT WE DO HERE BUT ALL THEY
PURSUE.
WE HAD SYMPOSIA COVERING THE
AREA AND A REPORT ON RACE,
ETHNICITY AND GENDER IN NEURAL
IMAGING PUBLICATIONS AND
RECOGNIZING THESE ARE IMPERFECT
MEASURES.
RACE IS NOT GROUNDED FIRMLY IN
SCIENCE SO MOVING FORWARD WE DO
NEED TO BE MINDFUL OF THE
HISTORIC RACISM EMBEDDED IN THE
FIELD WHEN COLLECTING DATA AND
KEEPING IN MIND SOCIAL ECONOMIC
FACTORS DO AFFECT THE BRAIN AND
NEED TO BE INCLUDED IN OUR
ANALYSIS BUT WE HAVE THE
RESPONSIBILITY TO DO SO IN A WAY
THAT IMPROVE DIVERSITY AND
REVEALS THE UNDERLYING BIOLOGY
AND BEING CAREFUL TO SAFEGUARD
THE DATA FROM MISUSE AS WE'VE
SEEN IN THE PAST.
THERE WAS A USER GUIDE TO THE
RESOURCES AND HERE THE GROUP
COVERED THE ORGANIZATION AND
ACCESS TO DATA GENERATED FROM
THE BRAIN INITIATIVE CELL CENSUS
PROJECT.
THERE'S HUNDREDS OF TERABYTES
AND THEY COVERED THE
REPLICABILITY OF THE SINGLE CELL
DATA.
LATER WE HAD THE NEUROMECHANISMS
ACROSS ORGANISMS.
ALL TALKS HIGHLIGHTED THE MOMENT
TO MOMENT VARIATION ACROSS
SPECIES FROM C ELEGANS,
ZEBRAFISH AND MICE AND
MONITORING NEURONS.
LOTS OF PROGRESS THERE.
FINALLY, THERE WAS A SYMPOSIUM
ON THE RESPONSIBLE RESEARCH AND
INNOVATION OF NOVEL NEURO
TECHNOLOGIES HIGHLIGHTS AGENCY,
RESPONSIBILITY AND ACCESS.
WE NEED TO BE MINDFUL OF THE
IMPLICATIONS OF WHAT WE'RE DOING
AS WE DEVELOP NEW TECHNOLOGIES
FOR HUMAN BRAIN DISORDERS.
YESTERDAY'S PANEL EXPLORED THE
NOVEL TECHNOLOGIES FOR A RANGE
OF CONDITIONS AND THESE
QUESTIONS OF AGENCY
RESPONSIBILITY AND ACCESS.
THE PANEL'S PRESENTATIONS DREW
UPON INTERVIEWS FROM
PARTICIPANTS AND SHED LIGHT ON
THE FIRST PERSON PERSPECTIVE AND
OPPORTUNITIES AND CHALLENGES
THEY FACED WHEN USING THE LIFE
CHANGING TECHNOLOGIES.
I'D LIKE TO UNDER SCORE THE MOST
IMPORTANT PERSPECTIVE AS WE
DEVELOP THESE NEW TECHNOLOGIES
FOR TREATING THE PATIENTS IS
PERSPECTIVE OF THE PATIENTS
THEMSELVES.
TODAY WE HAVE TWO UPCOMING
SYMPOSIA.
WE HAVE MORE POSTERS AND WE'LL
HAVE A TRAINEE HIGHLIGHT AWARD
TALKS, VERY EXCITING AND WE'RE
ALL LOOKING FORWARD TO ANOTHER
GREAT DAY OF SCIENCE AND WE'RE
GOING KICK IT OFF TODAY WITH A
PLENARY TALK FROM DR. KAFUI
DZIRASA FROM DUKE UNIVERSITY.
IT'S MY PLEASURE TO INTRODUCE
HIM.
THE ASSOCIATE PROFESSOR IN THE
DEPARTMENT OF PSYCHIATRY AND
BEHAVIORAL SCIENCES AT DUKE.
AND HAS JOINT APPOINTMENTS.
HE RECEIVED HIS BACHELOR'S
DEGREE FROM THE UNIVERSITY OF
MARYLAND COUNTY AND Ph.D. IN
NEUROBIOLOGY IF DUKE AND
COMPLETED RESIDENCY TRAINING IN
GENERAL PSYCHIATRY FROM DUKE IN
2016.
HE HAS A LONG STANDING INTEREST
IN CHANGES IN THE BRAIN CAUSE
NEUROLOGICAL AND MENTAL ILLNESS
AND HIS GRADUATE WORK LED TO
SEVERAL DISTINCTIONS AND WON ME
AWARDS FOR MOST OUTSTANDING
DISSERTATION THESIS AND THE UNCF
SCIENCE FELLOWSHIP AND WAKEMAN
FELLOWSHIP AND RECEIVED THE
LEADERSHIP AWARD IN 2007 AND
RECOGNIZED AS ONE OF EBONY
MAGAZINE'S 30 YOUNG LEADERS OF
THE FUTURE IN 2008.
HE'S RECEIVED THE RISING STAR
AWARD AND HIS LABORATORY IS
FEATURED ON "60 MINUTES" IN 2019
AND WON AN WARD FROM THE
PRESIDENTIAL EARLY CAREER AWARD
FOR SCIENTISTS AND ENGINEERS THE
NATION'S HIGHEST AWARD FOR
BEGINNING SCIENTISTS.
HE WAS RECOGNIZED IN 40 UNDER 40
IN THE NATIONAL MINORITY FORUM
AND HE WAS INDUCTED IN THE
AMERICAN SOCIETY FOR CLINICAL
INVESTIGATION IN 2019 ELECTED TO
THE NATIONAL ACADEMY OF MEDICINE
IN 2021 AND RECENTLY APPOINTED
AS AN INVESTIGATOR OF THE HOWARD
HUGHES MEDICAL INSTITUTE AND
SERVED AS AN ADVISER FOR THE
TRANSLATIONAL MEDICINE AND
MEMBER OF THE CONGRESSIONALLY
MANDATED RESEARCH INITIATIVE AND
EDITORIAL ADVISORY BOARD FOR TED
MED AND ALSO ON OUR BRAIN
MULTI-COUNCIL WORKING GROUP
WHICH ADVISES ME AND MY
COLLEAGUES FOR THE DIRECTIONS OF
WHERE WE'RE GOING AND JUST
APPOINTED TO THE NIH DIRECTOR'S
ADVISORY COUNCIL.
HIS ULTIMATE GOAL IS TO COMBINE
HIS RESEARCH TRAINING FOR
POPULATIONS SUFFERING FROM
PSYCHOLOGICAL ILLNESSES.
NOW TO KAF IN REWIRING NEURAL
CIRCUITS IN HEALTH AND DISEASE.
IT'S ALL YOURS.
>>I'M IN THE DEPARTMENT OF
PSYCHIATRY AND BEHAVIORAL
SCIENCES AND NEUROBIOLOGY AND
NEUROSURGERY AT DUKE.
I WANT TO WALK YOU THROUGH A SET
OF EXPERIMENTS WE'VE WORKED ON
IN THE LAST FEW YEARS TO THINK
ABOUT HOW WE ULTIMATELY REWIRE
OUR CIRCUITS IN HEALTH AND THIS
WAS FUNDED THROUGH A BRAIN
INITIATIVE R21 GRANT.
WHEN I START MY TALKS I THINK
IT'S IMPORTANT TO HIGHLIGHT THE
IMPACT MENTAL ILLNESS HAS HAD ON
INDIVIDUALS.
MENTAL DISORDERS LIKE DEPRESSION
AND ANXIETY AND POSTTRAUMATIC
DISORDER ARE DIFFICULT AND NOW
WITH THE GLOBAL PANDEMIC THE
INCIDENTS OF ILLNESSES HAVE
SKYROCKETED.
IF YOU LOOK AT EMERGING ADULTS
AND TEENAGERS, 130 HAVE DEALT
WITH SUICIDALITY IN THE LAST TWO
TO THREE YEARS.
ANY IMPACT THE ILLNESSES THESE
HAVE GONE UP AFFECTING OUR AND
I'VE BEEN WRESTLING WITH THIS
QUESTION NOT SIMPLY HOW TO
DIAGNOSE AND TREAT ILLNESSES BUT
COMING UP WITH THERAPEUTIC
STRATEGIES TO PREVENT THEM.
YOU'RE THINKING ABOUT PREVENTION
YOU NEED TWO THINGS.
WE SEE THIS THROUGH MEDICINE.
WE NEED TO PREDICT WHICH
INDIVIDUAL ARE AT RISK FOR
DEVELOPING THE ILLNESS SO YOU
HAVE TOO HAVE GOOD RISK
PREVENTION AND IDENTIFY THE
INDIVIDUALS AND INTERVENE
ULTIMATELY CHANGE THEIR DISEASE
TRAJECTORY.
NOW, THIS FRAMEWORK THAT I'VE
ALWAYS APPRECIATED SINCE EARLY
IN MEDICAL SCHOOL AND THIS IS
THERE IN CARDIOLOGY AND IN
CANCER AS WELL IF YOU THINK OF
THE INDIVIDUALS IN RED IN THE
BOTTOM RED HAND CORNER WHAT WE
TRIED TO DO IS MOVE THEM FROM
THE RED BOX TO THE RESILIENCE
CASE AND WE TRY TO DO THIS BY
CHANGING BLOOD PRESSURE IN THE
CASE OF SOME HEART DISEASE OR WE
TRY TO GET RID OF THE CANCER IN
THE CASE WITH SOMEBODY WITH
CANCER.
ONE THING I REGULARLY
APPRECIATED IN THE IN PATIENT
UNIT IS WHEN INDIVIDUALS CAME
IN, MANY TIMES THE WORSENING
SYMPTOMS WERE PROCEEDED BY A
MAJOR LIFE EVENT.
SOME STRESSFUL EVENT WHETHER IT
WAS THE FIRST TIME THE ILLNESS
WAS SHOWING UP OR ACUTELY GOT
WORSE.
IT TURNS OUT SEVERE
PSYCHOLOGICAL STRESS IS A RISK
FACTOR FOR MAJOR PSYCHIATRIC
ILLNESS.
I WANT TO ASK IS IT POSSIBLE TO
SEPARATE OUT INDIVIDUALS TO
PREDICT WHO WILL RESPOND WELL
AND WHO WILL BE RESILIENT.
SO IF WE SEPARATE OUT THE
INDIVIDUALS, PERHAPS WE CAN FIND
A BIOLOGICAL SIGNATURE WHICH IN
THIS CASE WE'LL CALL RISK AND
WE'RE ABLE TO FIND IT AND
PUBLISH IT AND THE WAY I THINK
OF THE BIOLOGICAL SIGNATURE IS
LIKE BLOOD PRESSURE OR
CHOLESTEROL IS A BIOLOGICAL
SIGNATURE FOR DEVELOPING HEART
DISEASE OR STROKE AND WALK YOU
THROUGH HOW WE DEVELOP THE
BIOLOGICAL SIGNATURE.
WE WORKED IN THE LAB PRIMARILY
BY RECORDING ELECTRICAL ACTIVITY
OF MANY BRAIN SITES
SIMULTANEOUSLY.
THE SAME WAY YOU RECORD ACTIVITY
IN THE SCALP EXCEPT ON THE TIPS
OF WIRES THAT HAD BEEN IMPLANTED
IN BRAIN FOR MANY SITES
SIMULTANEOUSLY AND THEN WE CAN
DO STANDARD ENGINEERING.
AND WE CAN TAKE ADVANTAGE OF
STATISTICAL FORECASTING.
AND WHAT WE ASK IS IF ACTIVITY
IN ONE BRAIN AREA CAN BE LINKED
OR CAN WE USE THAT TO PREDICT
FUTURE ACTIVITY IN ANOTHER BRAIN
AREA.
IN OTHER WORDS, IN ACTIVITY SAY
IN THE HIPPOCAMPUS LINKED TO THE
CORTEX AND WE CAN INFER IS
MOVING FROM ONE BRAIN AREA TO
ANOTHER.
INFER THE DIRECTIONALITY AND
LOOK AT THAT THE OTHER WAY.
IS INFORMATION IN ONE WAY LINKED
TO PAST INFORMATION IN THE OTHER
AREA AND IF IT IS WE INFER THE
INFORMATION IS IN THE OTHER
BRAIN AREA.
WE'RE SIMULTANEOUSLY COLLECTING
ALL THE DATA FROM MANY AREAS
SIMULTANEOUSLY AND SEE IF IT'S
SYNCHRONIZING AND LEADING AND
LAGGING AND ONCE WE COLLECT THE
INCREDIBLE AMOUNT OF INFORMATION
WE REALIZED WE HAD A CHALLENGE
IN MAKING SENSE OF IT.
WE REACHED OUT TO OUR COLLEAGUES
IN COMPUTER AND ELECTRICAL
ENGINEERING HERE AT DUKE AT THE
TIME AND NOW A FACULTY MEMBER,
DAVID CARLSON.
I'LL SHOW YOU THE SET OF
ALGORITHMS WE CAME UP WITH TO
MAKE SENSE OF THE DATA AND THIS
WILL BE IN A SET OF APPROACHES
CALLED MACHINE LEARNING OR
ARTIFICIAL INTELLIGENCE.
TO EXPLAIN THE MODEL I'LL USE
THE ANALOGY OF MUSIC.
WHEN YOU HEAR MUSIC YOUR SENSE
OF HEARING PRESSURE WAVES TRAVEL
THROUGH THE AREA AND THEY'RE
OSCILLATING ABOUT 10,000 TIMES
PER SECOND.
WHEN YOU THINK OF YOUR LOCAL
BRAIN WAVES THE EASIEST WAY TO
THINK ABOUT THEM IS LISTENING TO
BRAIN MUSIC.
AND THEN WE'LL TAKE THAT BRAIN
MUSIC AND CHUNK IT UP TO THE
FEATURES I JUST MENTIONED,
POWER, COHERENCE AND
DIRECTIONALITY AND WE'RE
ESSENTIALLY TAKING THE MUSIC AND
CHALKING IT UP AND ASK HOW DO
THE NOTES CHANGE TOGETHER OVER
SECONDS OF TIME?
WE'RE GOING TO DO THAT USING A
TOOL A MACHINE LEARNING TOOL
CALLED THE SUPERVISED AUTOTUNER.
WE'LL LEARN THE CORDS AND WHEN
NOTES ARE PLAYING TOGETHER AND
WHEN INSTRUMENTS ARE PLAYING
TOGETHER AND THEN APPLY LEVEL OF
ANALYSIS CALLED SUPERVISION AND
IT'S ESSENTIALLY GOING TO LEARN
THE CHORDS AND INSTRUMENTS
RELATED TO OUR BEHAVIOR OF
INTEREST.
IN OTHER WORDS, MOVING OR NOT
MOVING, FEEL OR NOT FEELING.
THIS PART OF THE MODEL
ESSENTIALLY LINKS THE CHORDS TO
BEHAVIOR AND FINALLY THERE'S A
FINAL PART OF THE MODEL THAT WE
BUILT IN AND THIS PART OF THE
MODEL IS BUILT IN SO IT
GENERALIZES IT.
THE BEST WAY TO THINK ABOUT IT
IS MAYBE YOU HEAR A TEMPO OR
DIFFERENT SET OF INSTRUMENTS YOU
STILL KNOW IT'S THE SAME SONG.
IF WE'RE GOING TO DISCOVER A
BRAIN STATE ASSOCIATED WITH
DEPRESSION OR ANXIETY WE WANT TO
MAKE SURE THAT IT'S GOING TO
WORK IN THE NEXT SET OF PATIENTS
THAT COME IN THE DOOR NOT ONLY
THE ONES WE SEE.
SO IF A NEW PATIENT COMES IN THE
MER
EMERGENCY ROOM WE WANT TO MAKE
SURE THE SIGNALS GENERALIZE TO
THIS PATIENT AS WELL.
HERE'S THE PARADIGM WE HAVE.
WE TAKE A SET OF ANIMALS AND
IMPLANT THEM IN MULTIPLE BRAIN
REGIONS IMPLICATED IN STRESS
BEHAVIOR.
AND THE CORTEX AND HIPPOCAMPUS
AND TWO VARIES OF THE CENTRAL
AMYGDALA AND THEN WE'LL RECORD
BRAIN ACTIVITY FROM ALL OF THESE
MICE WHEN THEY'RE BASICALLY IN
THEIR HOME CAGE RESTING AND WHEN
THEY'RE EXPOSED TO A MINOR LEVEL
OF AN AROUSAL EXPRESSER.
THEN WE'LL TAKE THE ANIMALS AND
EXPOSE THEM TO A REALLY BIG,
REALLY AGGRESSIVE MOUSE.
IT'S 50% BIGGER AND PICKED THE
MOST AGGRESSIVE MOUSE
ESSENTIALLY A TERMINATOR MOUSE.
WE'RE GOING TO GIVE IT ABOUT
FIVE MINUTES.
IT DOESN'T GO WELL FOR THE
FRIENDLY MOUSE AT ALL AND AT THE
END OF FIVE MINUTES WE HAVE TO
SEPARATE THEM AND LET THEM LIVE
NEXT TO EACH OTHER FOR 24 HOURS
AND THEY CAN SEE AND HEAR THE
TERMINATOR MOUSE IT'S LIKE AN
OLDER SIBLING.
SO THE MOUSE GETS BULLIED BY THE
TERMINATOR MOUSE AND AT THE END
OF 24 HOURS WE EXPOSE IT TO
ANOTHER BIGGER MOUSE AND IT GETS
EXPOSED AND IT'S BEAT UP BY 10
DIFFERENT MICE FOR 10 DIFFERENT
DAYS AND AT THE END OF THE
PROCESS THE MICE THAT HAVE BEEN
BEAT UP NO LONGER SLEEP WELL,
THEY NO LONGER ENJOY REWARDING
SUBSTANCES LIKE INTERACTING WITH
OTHER MICE OR SUGAR.
THEY HAVE ANXIETY LIKE PHENOTYPE
AS WELL AND THE SYNDROME OF THE
BEHAVIORS THAT ARE PROBLEMATIC
YOU CAN TREAT WITH MEDICATIONS
USED TO TREAT DEPRESSION,
ANXIETY AND PTSD IN HUMANS.
THE OTHER THING THAT'S IMPORTANT
ABOUT THE STRESS INDUCED
SYNDROME IS NOT ALL SHOW IT.
ABOUT 40% OF THE ANIMALS WE PUT
THROUGH THE PARADIGM HAVE NORMAL
BEHAVIOR ON THE OTHER SIDE, IN
OTHER WORDS, THEY'RE RESILIENT.
WE HAVE EVERYBODY'S BRAIN
ACTIVITY BEFORE STRESS AND THEN
WE KNOW WHO IS SUSCEPTIBLE AND
RESILIENT AFTER THE STRESSOR.
WE CAN SOLVE THAT MAP OR MODEL I
SHOWED ADDITIONALLY WHICH IS
FIGURING OUT WHAT VULNERABILITY
LOOKS LIKE IN THE BRAIN BEFORE
ANIMALS ARE STRESSED.
I'M GOING TO SHOW WHAT YOU THE
MAPS LOOK LIKE.
WE HAVE TWO OF THEM.
ON THE RIGHT I'M SHOWING THE MAP
OF WHAT THE BRAIN STATE LOOKS
LIKE IN THE ANIMALS THAT SHOW
THE STRESS-INDUCED PHENOTYPE.
AROUND THE RIM OF THE CIRCLE ON
THE TOP YOU SEE TO THE BRAIN
AREAS AND THEN YOU SEE
FREQUENCIES FROM ONE UP TO 50
HERTZ.
IF THERE IS COLOR AROUND THE
TIRE OF THE WHEEL IT MEANS THAT
BRAIN AREA IN THAT FREQUENCY
CONTRIBUTED TO THE CHORD BEING
PLAYED IN THE STRESS-INDUCED
BEHAVIORAL STATE.
IF THERE'S LINES CONNECTING,
SPOKES IN THE WHEEL, IT MEANS
THOSE TWO BRAIN AREAS ARE
SYNCHRONIZING AS PART OF THE
BRAIN NETWORK AND IF THEY'RE
SYNCHRONIZING THE DIRECTIONALITY
OF INFORMATION FLOW IS ON THE
BOTTOM AND THE ONE ON THE RIGHT
ARE STRESS-INDUCED DYSFUNCTION
AND ON THE LEFT IS ANIMAL BRAINS
BEFORE THEY'RE STRESSED.
THEY'RE BEHAVIOR LOOKS THE SAME
BUT THE CHORD IS PLAYING AND
THIS CHORD MEANS THE ANIMALS
WILL HAVE PROBLEMS IF THEY ARE
ULTIMATELY STRESSED.
YOU CAN SEE I COLOR CODED IT TO
MAKE IT EASIER.
THE MAPS LOOK DIFFERENT IN TERMS
OF THEIR COMPOSITION AND HOW
INFORMATION IS FLOWING THROUGH
THE BRAIN.
WE'RE ABOUT EIGHT SLIDES IN
ABOUT 10, 15 MINUTES IN AND YOU
CAN ALREADY SEE WE'VE SOLVED THE
CHALLENGE OF RISK PREDICTION.
AS I'M SURE YOU CAN APPRECIATE,
INTERVENING ON THOSE MAPS WAS
MUCH MORE OF A CHALLENGE AND
I'LL SPEND THE REST OF THE TALK
NAVIGATING HOE SET OF
EXPERIMENTS WE DID TO ULTIMATELY
GET TO PREVENTION IN THE LONG
RUN.
SO TO SHIFT THE IDEA OF
PREVENTION/INTERVENTION WE LIKE
TO USE ASSAYS IN THE LAW BROADLY
USED BY OTHER INVESTIGATORS.
TWO EXAMPLES ARE THE CLASSIC
SWIM AND TAIL SUSPENSION TASKS.
THESE HAVE BEEN USED AS ANIMAL
MODELS OF DEPRESSION.
I ALWAYS LIKE TO SAY IN MY
IMPRESSION, THESE TESTS DON'T DO
A SUFFICIENT JOB OF CAPTURING
THE BEHAVIORAL PROBLEMS OR
CHALLENGES OF THE PATIENTS I SEE
IN MY CLINIC SO I DON'T LIKE TO
FRAME THESE AS MODELS OF
DEPRESSION.
THERE'S TWO FEATURES OF THE TASK
I THINK ARE PARTICULARLY
IMPORTANT FOR USING THEM IN THE
STRATEGY FOR PREDICTION.
I THINK THESE FEATURES ARE
WIDELY ACCEPTED.
THE FIRST IS THAT IF YOU EXPOSE
AN ANIMAL TO THESE ASSAYS
PUTTING AN ANIMAL IN A TANK OF
WATER IT CAN'T ESCAPE OR BY ITS
TAIL THESE ASSAYS STRESSFUL.
WE KNOW THAT BECAUSE YOU CAN SEE
AN INCREASE IN THE ANIMAL'S
STRESS HORMONES.
YOU CAN MEASURE THEIR BLOOD AND
THE STRESS HORMONES GO UP.
IT'S CLEAR THE TASKS ARE
STRESSFUL.
THE SECOND FEATURE OF THE TASKS
PARTICULARLY IMPORTANT IS THAT
THE ANIMALS BEHAVIOR IN THESE
ASSAYS HOW MUCH THEY MOVE AND
TRY TO GET OUT OF THE SITUATIONS
IS RELATED TO THE ANIMAL'S PRIOR
EXPRESS EXPOSURE.
IF YOU EXPOSE THE ANIMALS TO A
LOT OF STRESS AHEAD OF TIME THEY
MOVE SUBSTANTIALLY LESS IN THE
ASSAYS.
THOSE ARE THE CRITICAL FEATURES
WE USED TO DO OUR WORK WITH
THESE ASSAYS.
IF YOU LOOK AT THE ORIGINAL
LITERATURE IT LOOKED LIKE THEY
TOOK ADVANTAGE OF THE TWO
FEATURES IN THE TASK.
THEY RAN THE TASK TWO DAYS IN A
ROW.
YOU PUT THE ANIMAL IN THE TASK
AND GIVE AN ANTIDEPRESSANT
BETWEEN THE TWO DAYS AND RUN IT
AGAIN THE NEXT DAY.
IT MEANS PERHAPS THEY WERE
CAPTURING HOW THE BRAIN ADAPTS
IN RESPONSE TO A PRIOR STRESS
EXPOSURE.
WE RAN THE TASK OVER TWO DAYS.
IN THE SAME CONTEXT WE CAN ASK
HOW THE BRAIN RESPONDS TO AN
EXPOSURE TO STRESS.
THE DIFFERENCE ON THE SECOND DAY
THE ANIMAL HAS HAD A PRIOR
EXPRESS EXPOSURE.
WE'RE ASKING HOW THE COMPUTATION
CHANGE IN THE SAME STRESS
CONTEXT FROM DAY ONE AND DAY
TWO.
SO WHAT WE'RE GOING TO DO IS
WE'RE GOING TO LOOK AT THE
ANIMAL'S BEHAVIOR AND PHYSIOLOGY
AND TO SHOW YOU WHAT THE
BEHAVIOR LOOKS LIKE.
ON THE LEFT YOU SEE THE TAIL
SUSPENSION CASE AND MEASURE HOW
MUCH TIME THE ANIMAL SPENDS
MOBILE AND YOU MAY HEAR FREEZING
AND HOW MUCH TIME IT SPENDS NOT
MOVING IN THE ASSAY AND SHOWING
ANIMALS ON DAY ONE AND TWO AND
THIS IS THE SAME MOUSE.
AS A POPULATION THE ANIMAL
BECOME MORE MOBILE ON THE SECOND
DAY OF THE ASSAY COMPARED TO THE
FIRST DAY.
THERE'S INDIVIDUAL DIFFERENCES
IN THE POPULATION.
NOT ALL BECOME MORE MOBILE BUT
BECOME MORE AS A POPULATION.
IF YOU LOOK AT THE SAME ANIMALS
IN A DIFFERENT CONTEXT YOU PUT
THEM IN AN EMPTY OPEN BOX THAT
IS NOT STRESSFUL THE ANIMAL
STAYS CONSTANT.
WE'RE GOING TO PLANT THEM WITH
ELECTRODES IN THE CORTICO BRAIN
REGIONS INVOLVED IN STRESS
BEHAVIOR AND MEASURE NEUROPHYSIO
ACTIVITY AND MEASURE BRAIN WAVES
AND THE ACTIVITY OF INDIVIDUAL
CELLS WITHIN THE BRAIN AREAS AND
ASK HOW THE COMPUTATIONS CHANGE
WHEN THEY MOVE.
WE ARE TAKING BRAIN CELLS AND
ASKING HOW THE COMPUTATIONS DAY
FROM DAY ONE OR DAY TWO.
ARE THERE MORE OR LESS CELLS
RECORDING THE MOVEMENT IN THE
STRESS-RELATED CONTEXT.
ONLY TWO AREAS WE LOOKED AT
CHANGED.
THE INFRALIMBIC CORTEX AND MD
THALAMUS.
THESE BECOME OUR CANDIDATE BRAIN
AREAS.
WHEN WE LOOK AT CELLS WE PULL
THEM FROM THE ANIMALS RECORDED
AND WE'LL LOOK AT A SIGNAL WE
GET FROM EVERY ANIMAL.
FIRST WE'LL LOOK AT THE
INFRALIMBIC CORTEX OR THALAMUS
ALONE AND DAY ONE IN RED AND DAY
TWO IN GRAY.
THERE'S NO DIFFERENCE BETWEEN
DAY ONE OR DAY TWO FOR THE BRAIN
AREAS.
THERE'S A DIFFERENCE IN HOW
SYNCHRONIZE AND THERE'S NO
DIFFERENCES IN THE
DIRECTIONALITY ON THE BOTTOM.
WE COULDN'T FIND THE DIFFERENCE
IN THE FEATURES WE LOOKED AT ON
THE MAP BUT THEN IT OCCURRED TO
US THERE'S ACTUALLY A DIFFERENT
WAY IN WHICH BRAIN ACTIVITY CAN
SYNCHRONIZE AS WELL.
IF YOU THINK ABOUT THIS IN MUSIC
THE BEST WAY TO PICTURE THIS IS
TO THINK OF MOVING SYNCHRONIZING
LEFT, RIGHT, RIGHT OR LEFT,
RIGHT, RIGHT OR LOOKING AT THE
MIRROR IMAGE.
THE IDEA IS YOU CAN HAVE THEM
SYNCHRONIZING BETWEEN TWO
FREQUENCIES.
A SHORTER AND FASTER FREQUENCY.
THIS IS CROSS-FREQUENCY
COUPLING.
YOU CAN SEE THE LOWER
OSCILLATION IN GREEN AND HIGHER
FREQUENCY OSCILLATION IN RED IN
THE BURST OF ACTIVITY OR
INCREASES IN AMPLITUDE YOU CAN
SEE THAT AS A SPECIFIC PHASE OF
THE CYCLE IN GRAY.
WE'LL SEE IF THIS PROPERTY
HAPPENS BETWEEN THE INFRALIMBIC
CORTEX AND MEDIAL THALAMUS AND
THIS CAME UP YOU CAN SEE THE
FREQUENCIES OF INFRALIMBIC
CORTEX ON THE X AND THALAMUS ON
THE Y.
IF THERE'S BLUE IT MEANS THE TWO
FREQUENCIES DON'T SYNCHRONIZE
AND IF THERE'S RED THERE'S
STRONG SYNCHRONY AND SEE THE
COUPLING AND ON THE RIGHT I'M
SHOWING THE STRENGTH OF THE
COUPLING AGAIN DAY ONE IN GRAY
AND DAY TWO IN RED AND THIS
COUPLING DOES INCREASE BETWEEN
DAYS.
SO WHAT THIS SUGGESTS IS WE
INDEED CAN FIND A SIGNATURE
RELATED TO THE ANIMAL'S BEHAVIOR
CHANGE.
SO WE'RE EXCITED ABOUT THIS.
THEN WE IMMEDIATELY RAN INTO A
QUESTION WE NEEDED TO ANSWER.
AND THAT QUESTION IS IS THIS
SIGNATURE THE PROBLEM?
IS IT PRIMARY?
IF THIS SIGNATURE'S PRIMARY IT
MEANS IT IS CONTRIBUTING TO WHY
THE ANIMALS ARE MORE MOBILE ON
THE SECOND DAY COMPARED TO THE
FIRST.
AND SO IF YOU WANT TO COME UP
WITH A THERAPEUTIC YOU HAVE TO
FIGURE OUT HOW TO PREVENT IT OR
GET RID OF IT BECAUSE IT'S
PRIMARY.
ON THE OTHER HAND WHAT WE
APPRECIATE FROM AN ENGINEERING
PERSPECTIVE IS THE SIGNATURE CAN
BE COMPENSATORY.
WHAT I MEAN IS SAY YOU RUN UP A
FLIGHT OF STAIRS, YOUR HEART
RATE GOES FASTER AND THE REASON
THE HEART RATE GOES FASTER IS
BECAUSE MUSCLES NEED MORE OXYGEN
AND THE HEART IS TRYING TO
COMPENSATE BY GIVING THE MUSCLES
MORE OXYGEN SO IF IT'S
COMPENSATORY IT'S TRYING TO
COUNTER A PROBLEM AND IF YOU
WERE TO COME UP WITH A
TECHNOLOGY THAT GOT RID OF IT
YOU'D MAKE PEOPLE WORSE.
WE NEED TO KNOW WHETHER THE
SIGNATURE IS PRIMARY OR
COMPENSATORY SO WE KNOW HOW TO
APPROACH A THERAPEUTIC.
THE PROBLEM IS THERE'S NO GREAT
WAY OF GENERATING THE SIGNATURE
TO FIGURE OUT IF IT'S PRIMARY.
IF IT'S PRIMARY AND YOU CREATE
IT, THE ANIMAL SHOULD GET WORSE
AND IF IT'S COMPENSATORY THE
ANIMAL SHOULD IMPROVE.
WE CAME UP WITH A STRATEGY.
SOME INITIAL WORK WAS DONE BY
MYSELF AND AN UNDERGRAD NEIL
GALLER AND WALK YOU THROUGH WHAT
WE'RE TRYING TO DO AS A
SCHEMATIC.
WE DECIDED WE NEEDED TO RECORD
OR EXTRACT THE BRAIN WAVE FROM
INFRALIMBIC CORTEX IN REAL TIME
AND PLAY A HIGHER FREQUENCY INTO
THE MEDIAL DORSAL THALAMUS USING
THE SIGNATURE IN REAL TIME.
A CLOSED-LOOP MODULATION
STRATEGY.
THE WAY WE'RE GOING TO DO THIS
IS USE OUR STANDARD RECORDING
TECHNOLOGY AND THEN WE'RE GOING
STIMULATE CELLS OR ACTIVATE THE
CELLS IN THALAMUS USING A TOOL
MOST THE INVESTIGATORS ARE
FAMILIAR WITH.
OPTOGENETICS AND IT'S BASICALLY
THE SAME TYPE OF PROTEIN IN YOUR
LIE THAT CHANGES LIGHT TO BRAIN
ENERGY.
HERE THE ONLY DIFFERENCE IT'S AN
ION CHANNEL AND LETS POSITIVE
IONS IN, LIGHT TO BRAIN
ELECTRICITY.
WE'LL EXPRESS THIS CHANNEL IN
CELLS AND THALAMUS AND
PARTICULARLY THE CELLS THAT MAKE
CONNECTIONS OR PHYSICAL
CONNECTIONS WITH THE CELLS IN
THE INFRALIMBIC CORTEX AND USE
AN ENTEROGRADE CREE AND THEN
WE'LL HOOK IT UP TO OUR
ENGINEERING SYSTEM WHICH IS
GOING TO EXTRACT BRAIN
OSCILLATIONS FROM REAL TIME FROM
THE ANIMAL'S INFRALIMBIC CORTEX
AND READING AND WRITING THE
SIGNATURE IN THE ANIMAL'S BRAIN
AND WE'LL USE THE PROTEIN
ACTIVATED BY BLUE LIGHT.
IN OTHER WORDS, BLUE LIGHT WILL
CAUSE THE BRAIN TO BE STIMULATED
AND YELLOW LIGHT DOES NOTHING.
HERE'S ON THE UPPER LEFT HAND
CORNER.
THE BRAIN WAVE AND SHOWING THANK
YOU LASER FIRING IN BLUE THE TWO
ARE SYNCHRONIZED.
WHEN WE LOOK AT THE ANIMALS
BEHAVIORALLY LOOK AT THE YELLOW
LIGHT OVER 10 MINUTES THE
ANIMALS BECOME MORE MOBILE.
WHEN WE COMPARE THE BLUE LIGHT
TO THE YELLOW LIGHT THE ANIMAL'S
STIMULATED WITH THE BLUE LIGHT
SHOW LESS BEHAVIORAL ADAPTATION
IN THE ASSAY.
IN OTHER WORDS, LESS IMMOBILITY
AND PLAYING IT IN THE ANIMAL'S
BRAIN INDUCES A COMPENSATORY
RESPONSE.
IT SHOWS A GREATER DEAL OF
COMPENSATION TO THE EXTERNAL
STRESSOR.
WE ALSO DID TWO CONTROLS WE
THOUGHT WERE PARTICULARLY
IMPORTANT.
IN THE FIRST SET WE STIMULATE
THE SAME CELLS IN THE MEDIAL
DORSAL THALAMUS BUT NOT WHERE
WE'RE READING AND PLAYING THE
SIGNATURE IN.
WE'RE JUST GOING TO DO AN OPEN
LOOP PLAY THE SAME NUMBER OF
LIGHT PULSES INTO THE MEDIAL
DORSAL THALAMUS AND THE ANIMAL'S
BEHAVIOR GETS WORSE.
THEY SHOW INCREASED IMMOBILITY
COMPARED TO THE ANIMALS
STIMULATED WITH YELLOW LIGHT.
WE'RE NOT JUST STIMULATING THE
RIGHT CELLS IN THE RIGHT SPACE
THE TIMING MATTERS.
THEN WE DID ONE MORE CONTROL IN
WHICH QUE ASKED, WELL, IS IT
BECAUSE WE'RE STIMULATING IN THE
BURSTING PATTERN IN THE FIRST
CASE AND NOT USING THAT IN THE
SECOND PHASE.
WE STIMULATED WITH ANOTHER SET
OF TRIPLETS NOT TIMED TO THE
LOCAL OSCILLATION.
IN OTHER WORDS, IT'S AN OPEN
LOOP TRIPLET PATTERN AND THE
ANIMAL'S BEHAVIOR DIDN'T CHANGE
AT ALL.
IN OTHER WORDS, YOU NEED IT TO
READ INFORMATION FROM ONE BRAIN
AREA AND PLAY THAT INFORMATION
INTO THE OTHER BRAIN AREA IN
ORDER TO ACTIVATE THE CIRCUIT IN
THE CORRECT WAY.
WE'RE EXCITED.
WE COME UP WITH THIS
CLOSED-STIMULATION PATTERN WE
THOUGHT WOULD BE A GREAT
STRATEGY FOR PLAYING OR
ACTIVATING CIRCUITS IN THE BRAIN
NECESSARY TO IMPROVE RESILIENCE.
WE STARTED THINKING HOW TO APPLY
THIS FOR STRESS-INDUCED
BEHAVIORAL DISORDERS.
AT THE TIME I HAD A CHANCE TO
VISIT SOME FAMILY MEMBERS.
MY PARENTS MIGRATED HERE FROM
GHANA IN WEST AFRICA AND ONE OF
MY SIBLINGS, FOUR OF THE FIVE
CARRY A MAJOR PSYCHIATRIC
DISORDER WHETHER IT'S DEPRESSION
OR ANOTHER DISORDER AND I TALKED
ABOUT THE TECHNOLOGY AND HELPING
PREVENT MAJOR PSYCHIATRIC
DISORDERS MY UNCLE WHO IS SUPER
PROUD OF ME AND POINTED OUT AND
ASKED A QUESTION THAT STUCK WITH
ME AND HE SAID THIS IS
FANTASTIC.
YOU'VE COME UP WITH TE IDEA OF
MINIATURIZING THE STIMULATION
BUT TELL ME MORE HOW IT WILL GET
TO THE THIRD WORLD TO HELP?
I WAS STUCK BECAUSE I DIDN'T
HAVE AN ANSWER AND I REALIZED
THE TECHNOLOGY WASN'T GOING TO
SCALE IN A WAY THAT WOULD
ULTIMATELY GET TO THE THIRD
WORLD.
SO I WENT BACK TO THE DRAWING
BOARD IN HOW WE CAN COME UP WITH
PREVENTIVE STRATEGIES AT SCALE.
DEALING WITH THE MOST
DEBILITATING DISORDERS IN THE
WORLD ONE ESTIMATE SAYS ONE IN
THREE PEOPLE SUFFERS FROM THESE
CHALLENGES PARTICULARLY THROUGH
THE PANDEMIC.
WE NEED TECHNOLOGY THAT WILL
SCALE TO THE SIZE AND SCOPE OF
THE ILLNESSES.
SO FOR THE REMAINDER OF THE TALK
I'M GOING TO WALK YOU THROUGH
OUR STRATEGY TO COME UP WITH
SCALABLE SOLUTION TO THIS
PROBLEM.
SO WE ASKED OURSELF THE
QUESTION, WHAT ARE THE TYPES OF
TREATMENTS THAT ULTIMATELY
SCALE?
ONE, PHARMACOLOGY.
WHEN WE APPRECIATED HERE WAS WE
NEEDED SOMETHING THAT WAS GOING
TO WORK FASTER THAN THE TIME
SCALE THAT SOMETIMES
PHARMACOLOGY OPERATES AT.
SO WE ULTIMATELY TOOK A STEP
BACK AND WE THOUGHT ABOUT TWO
TECHNOLOGIES THAT HAVE SCALED
WELL TO DEAL WITH ILLNESS.
ONE OF THEM CERTAINLY
PHARMACOLOGIC AND ONE IS
ANTIBIOTICS AND THE SECOND IS
VACCINES.
WE THOUGHT ABOUT THESE
CONCEPTUALLY.
WHAT ANTIBIOTICS DO IS THEY WORK
IN THE BOUNDARY TO FIGURE OUT
NOT SELF-VERSUS SELF-AND THEN
TARGET NON-SELF AND SPARE SELF.
IN OTHER WORDS, THEY ATTACK
THINGS THAT AREN'T SELF AND DO
THEIR BEST JOB TO SPARE SELF.
WE REALIZED AT THEIR CORE,
NEUROPSYCHIATRIC ILLNESSES ARE
SELF.
THEY'RE OF THE BRAIN.
SO WE CONSIDERED THE IDEA OF
WHAT VACCINES DO AND THEY
ULTIMATE TARGET SELF AND TRY TO
MAKE SELF MORE RESILIENT TO THE
ENVIRONMENT.
SO IT'S A CONCEPT WE THOUGHT HAD
POTENTIAL FOR HOW TO COME UP
WITH A PREVENTATIVE THERAPEUTIC.
IT SO HAPPENS AT THE TIME I WAS
WORK WITH INVESTIGATORS THINKING
ABOUT THE SECOND HALF OF THE
BRAIN INITIATIVE AND I WAS
WONDERING A LOT ABOUT FANTASTIC
TECHNOLOGIES WHETHER IT'S A
HUMAN BRAIN CELL ATLAS WORKED ON
BY JOHN AND MY COLLEAGUE HERE AT
DUKE OR TOOLS THAT WOULD ALLOW
US TO USE VIRUSES ACROSS THE
BLOOD BRAIN BARRIER AND
COLLEAGUES LIKE VIVIANA AT CAL
TECH AND WHAT THE TWO
TECHNOLOGIES IF WE TOOK A STEP
BACK THEY WOULD CREATE
TREMENDOUS POTENTIAL WE CAN USE
TO THINK ABOUT HOW TO INTERVENE
ON THE DISORDERS.
WHAT THE HUMAN BRAIN CELL ATLAS
IF SUCCESSFUL WOULD GIVE OUT THE
GENE EXPRESSION OR CODE FOR
SPECIFIC CELL TYPES IN THE BRAIN
AND IDENTIFY AND LOCATE SPECIFIC
BRAIN CELLS IN THE HUMAN BRAIN.
WHAT THE AAV OR VIRUSES ACROSS
THE BLOOD BRAIN BARRIER WOULD
ALLOW TO US DO IS USING THE GPS
CODE WE CAN DELIVER PROTEIN
CODES TO SPECIFIC CELL TYPES IN
THE BRAIN.
AND IF YOU PUT THE TWO TOOLS
TOGETHER AND ULTIMATELY GOT THEM
TO WORK, WHAT THAT WOULD MEAN IS
THAT WE COULD, IF WE FIGURED OUT
HOW TO TAKE THE LARGE CLOSED
LOOP INSILICO SYSTEM, IF WE
FIGURED OUT HOW TO TURN THEM
INTO PROTEINS WE'D BE ABLE TO
COMBINE THEM WITH THE DELIVERY
SYSTEM AND PUT THIS CLOSED LOOP
STIMULATOR IN THE BRAIN.
WE JUST HAVE HAVE TO FIGURE OUT
HOW TO TURN THEM INTO PROTEINS.
THE CHALLENGE OF FIGURING OUT
HOW TO TURN THE SYSTEM INTO
PROTEINS.
SO IT TURNS OUT THAT THE BODY
HAS EVOLVED WAYS OF MOVING
ELECTRICAL ACTIVITY FROM ONE SET
OF CELLS TO ANOTHER.
THIS FORM OF MOVING ACTIVITY
FROM ONE SET OF CELLS TO ANOTHER
HAPPENS IN MANY TISSUES IN THE
BRAIN.
WE CAN APPRECIATE THIS IN THE
HEART AND BRAIN AS WELL.
IT DOES THIS THROUGH A SET OF
CHANNELS CALLED ELECTRICAL
SYNAPSES OR GAP JUNCTIONS.
THE GAP JUNCTIONS ARE
ESSENTIALLY IN MAMMALS AND SET
OF PROTEINS AND 20 COME TOGETHER
TO FORM A HEMI CHANNEL AND THEN
FORM A GAP JUNCTION OR
ELECTRICAL SYNAPSES AND THEY
ALLOW IONS TO FLOW BACK AND
FORTH AND THEY'RE ELECTRICITY.
THEY'RE EXPRESSED IN MOST
TISSUES IN THE BODY.
SO THE CHALLENGE IS IF YOU WANT
TO COME UP WITH A STRATEGY TO
ESSENTIALLY READ FROM ONE SET OF
BRAIN CELLS AND PLAY THAT
ELECTRICAL ACTIVITY IN ANOTHER
YOU MAY WANT A STRATEGY LIKE
THIS.
IN PINK I HAVE TAKEN THE TWO
PRESYNAPTIC NEURONS AND INSERTED
GAP JUNCTION IN PINK.
AND YOU WANT TO TRANSFER THE
ELECTRICAL ACTIVITY TO THE
POST-SYNAPTIC CELL.
IF YOU TRIED TO DO THIS YOU'D
INVERT THE ELECTRICAL SYNAPSES
OR GAP JUNCTIONS ALL OVER THE
PLACE.
AND IF YOU THEN WERE READING
ELECTRICAL ACTIVITY FROM THE
PRESYNAPTIC CELL YOU'D START
SCRAMBLING THE MUSIC IN A WAY
YOU DIDN'T WANT TO.
THE OTHER PROBLEM IS THESE
ELECTRICAL SYNAPSES ARE
ESSENTIALLY FORCED.
YOU'D BE SPENDING ELECTRICAL
INFORMATION IN THE WRONG
DIRECTION LIKE TRYING TO HAVE A
CONVERSATION WITH SOMEONE
SCREAMING AT YOU.
WE TRIED THE EXPRESSED THE
ELECTRICAL SYNAPSES IN THE HY
HYPE -- HIPPOCAMPUS AND THE
ANIMALS STARTED SEIZING AND IT'S
NOT A MODIFIABLE WAY TO DO THIS
IN ANIMALS.
WHAT I WANT TO DO AND I
APOLOGIZE TO EVERYONE IN THE
AUDIENCE WHO IS COLOR-BLIND,
WHAT YOU WANT TO DO IS MAKE A
COMBINATION OF NEW ELECTRICAL
SYNAPSES.
I'M SHOWING IN GREEN YOU'D WANT
A PAIR.
YOU'D WANT A POS AND NEGATIVE
MAGNET LIKE A KEY WHERE THE KEY
WOULDN'T COMBINE WITH THE KEY
BUT WHEN THEY COME TOGETHER
YOU'LL FORM THE ELECTRICAL
SYNAPSES AND YOU'D WANT IT TO DO
RECTIFICATION AND FLOW IN ONE
DIRECTION.
SO WE HAVE THIS CONCEPT AND WE
PULLED TOGETHER WHAT I CALL OUR
DREAM TEAM TO START WORKING ON
IT.
I CALL THEM MY DREAM TEAM
BECAUSE THEY'RE UNDER GRADS AND
WHAT IS SO BEAUTIFUL AND AMAZING
ABOUT YOUNG SCIENTISTS THEY'RE
OFTEN NOT JADED BY CONSTANTLY
HEARING ABOUT WHAT ISN'T
POSSIBLE.
SO WE SET THEM ON THIS TASK TO
IDENTIFY THE CUSTOM BARE OF
ELECTRICAL SYNAPSES.
THEY RED EVERYTHING THERE WAS TO
READ ABOUT MAMMALIAN PROTEINS
AND SYNAPSES AND READ ABOUT
INVERTEBRATES AND READ ABOUT
DIFFERENT PROTEINS AND CONVERGED
ON THIS AND THIS PAIR HAD
SEVERAL FEATURES.
FIRST, AND TWO DIFFERENT
PROTEINS COME TOGETHER TO FORM A
GAP JUNCTION.
THE CURRENT IS BIAS AND THE
ELECTRICAL PROPERTIES IS FORMED
BETWEEN THE TWO PROTEINS TENDS
TO WORK IN A RANGE COMPATIBLE
WITH WHAT WE'D WANT IT SEE IN A
MAMMALIAN NERVOUS SYSTEM.
NOW, THERE'S A PARTICULAR
PROBLEM WITH THIS PAIR.
WHILE 34.7 DOCKED AND BOUND WITH
34.7 OR 35, THEY ALSO DOCKED
WITH THEMSELVES.
SO INDEED, THEY WORK LIKE A LOCK
AND KEY BUT IN THIS CASE THE
LOCK COMBINED WITH THE LOCK AND
THE KEY COMBINED WITH THE KEY.
WE REALIZED WE'D HAVE TO SOLVE
THE CHALLENGE OF PREVENTING THE
TWO PROTEINS FROM BINDING FROM
THEMSELVES.
IT TURNS OUT THE DOCKING
FEATURES THE FEATURES THAT
DECIDE HOW THESE TWO PROTEINS
COME TOGETHER IS LARGELY BASED
IN THE EXTRA CELLULAR LOOP OF 1
AND 2.
SOME KNOWLEDGE WAS KNOWN AND
WHAT WAS REALLY FUN FOR ME AT
THE TIME IS HAVING NOT DONE VERY
WELL IN BIO CHEMISTRY AS A
MEDICAL STUDENT.
I WAS TIME TO EXPAND FROM MY
KNOWLEDGE BASE AND BRING IN
WONDERFUL COLLABORATORS WITH A
BETTER EXPERIENCE IN BIO CLEM --
BIO CHEMISTRY WE RECRUITED A
BRILLIANT YOUNG SCIENTIST TO A
POST-DOC AND THE LAB AND WHAT WE
WERE ABLE TO COME UP WITH AND
I'LL SHOW YOU THIS WAS A
STRATEGY TO DETERMINE THE
RESIDUES ON THE LOOPS WHICH
CONTROLLED DOCKING AND MIX THEM
AROUND UNTIL WE CAN CREATE A
CUSTOM LOCK AND KEY.
HERE'S HOW WE DID THAT.
WE BASICALLY TOOK THE EXTRA
CELLULAR RESIDUES AND CRA CREAT
MUTATIONS AND TOOK THE POSITIVE
AMINO ACID RESIDUES AND MADE
THEM NEGATIVE AND CREATED A
BUNCH OF MUTANTS AND THEN WE
WORKED THROUGH TO CREATE A
SCREEN TO DETERMINE HOW THOSE
PROTEIN PAIRS WERE DOCKING WITH
EACH OTHER AND IN THE INTEREST
OF TIME I WON'T WALK YOU THROUGH
ALL THE THINGS THAT DIDN'T WORK.
THESE THE STRATEGIES THAT WERE
WRITTEN INTO THE AIMS OF OUR
BRAIN INITIATIVE APPLICATION.
AFTER A FEW YEARS OF
EXPERIMENTING I'LL SHOW YOU THE
STRATEGY THAT LIZ WAS ABLE TO
COME UP WITH.
SO AFTER MANY MANY FAILED
ATTEMPTS AT OUR ORIGINAL
APPROACH, SHE DUG INTO WHAT IS
THE CONEXON LIFE CHANNELS AND
TWO PROTEINS FORM THE GAP
JUNCTION AND WHEN YOU WANT TO
ESSENTIALLY TURN IT OFF OR DOWN
REGULATE IT THE GAP JUNCTIONS
ARE RIPPED A PART BETWEEN THE
TWO TO FORM JUST THE SINGULAR
HEMI CHANNELS AGAIN.
THE WHOLE THING IS SWALLOWED OR
INTERNALIZED INTO A CELL.
SO WHAT SHE REALIZED SHE COULD
DO IS JUST LABEL THE CELLS OR
FLUORESCENTLY TAG THEM AND ONE
HAD GREEN TAGGED CONNECTIONS AND
THE OTHER ONE WE COULD TAG WITH
A RED GLOWING FLUORESCENT
PROTEIN SO IF A GAP JUNCTION IS
FORMED IT'S INTERNALIZED AND YOU
SHOULD BE ABLE TO SEE GREEN AND
RED INSIDE THE SAME CELL.
I'LL SHOW YOU A MOVIE ON WHAT
THIS LOOKS LIKE.
PAY ATTENTION TO THE UPPER LEFT
HAND CORNER AND HERE I'M SHOWING
THE KIDNEY CELLS THE 293s AND
I'M JUST WE HAVE A GREEN
POPULATION, A RED TAG POPULATION
AND WHAT YOU'RE LOOKING FOR ARE
CELLS THAT HAVE GREEN AND RED IN
THEM AND YOU CAN SEE THAT OVER
TIME IN THE UPPER LEFT HAND
CORNER YOU CAN SEE CELLS WITH
THE GREEN AND RED IN THEM THAT
START SHOWING UP.
HERE'S OUR STRATEGY HOW WE'LL DO
THIS.
DR. RANSY IS GOING TO GREEN TAG
A PROTEIN AND EXPRESS IT IN HECK
CELLS AND EXPRESS THE OTHER IN
ANOTHER POPULATION OF HEX CELLS
AND COINCUBATE THEM TOGETHER AND
THIN ESSENTIALLY PUT THE HEK
CELLS THROUGH FLOW CYTOMETRY.
THIS IS A SITUATION IN WHICH THE
PROTEINS DO NOT DOCK, THAT DO
NOT FORM A GAP JUNCTION AND YOU
SEE THE MAP ON THE BOTTOM RIGHT
AND YOU ONLY SEE BASICALLY A
VERTICAL LINE AND HORIZON THAT
WILL LINE AND THE VERTICAL LINE
MEASURES HOW MUCH GREEN
FLUORESCENT THERE IS IN EACH
CELL AND YOU SEE OF GREEN
FLUORESCENT OR A LOT AND ON THE
NEXT LINE RED FLUORESCENT, A
LITTLE BIT OR A LOT AND YOU
DON'T SEE CELLS THAT HAVE GREEN
AND RED.
YOU SEE GREEN OR RED.
ON THE PLOT ABOVE THAT I'M
SHOWING A SITUATION IN WHICH THE
CONNEXOSOMES PROTEINS AND CAN
YOU SEE BLUE DOTS OFF THE
VERTICAL OR HORIZONTAL AXIS.
IN THIS CASE 17% OF THE CELLS
ARE OFF THE AXIS.
THE TOP IS THE CONNECTION IN
WHICH THE PROTEINS DO DOCK.
HERE'S THE SET UP.
WE'RE GOING TO EN ROUND ONE
WE'RE GOING SCREEN ALL OF OUR
CONNEXOSOMES MUTANTS AGAINST
THEMSELVES AND LOOK FOR MUTANT
DON'T DOCK THEMSELVES.
IN ROUND TWO WE'LL SCREEN ALL
THE PROTEINS THAT DON'T DOCK
WITH THEMSELVES AGAINST EACH
OTHER LOOKING FOR A PAIR THAT
DOCKS WITH A COUNTERPART BUT NOT
ITSELF AND THE ROUND THREE
BECAUSE THE ULTIMATE GOAL IS TO
DEVELOP A HUMAN THERAPEUTIC
WE'LL SCREEN THIS AGAINST THE
PROTEINS IN THE HUMAN BRAIN.
THE CONNEXOSOME 33 AND 36.
WE HAD 140 MUTANTS AND 15
SURVIVED THE FIRST ROUND OF THE
SCREEN.
AND THEN WE SCREENED THEM
AGAINST EACH AND HAD THREE PAIRS
THAT SURVIVED.
OUT OF 140 CANDIDATES WE HAD
THREE PAIRS THAT SURVIVED THE
SECOND ROUND AND THEN WE
SCREENED THEM AGAINST THE MAJOR
CONNEXOSOMES PROTEINS AND NONE
OF THE PAIRS SURVIVED.
SO MAJOR PROGRESS BUT WE WEREN'T
ULTIMATELY GOING TO ACHEF OUR
GOAL HERE OF COME UP WITH A WAY
OF REWIRING HUMAN NEUROCIRCUITS.
MORE TROUBLING, THE PROCESS
OCCURRED IN SPRING 2020 AND LIKE
THE REST OF MY COLLEAGUES HERE,
OUR LAB SUDDENLY SHUT DOWN AND
WE ALL WENT HOME AND SHIFTED OUR
EXPERIMENTAL DIRECTION ENTIRELY
WHERE WE ALL SUDDENLY BEGAN
WORKING WITH YEAST AND MAKING
BREAD AND COOKIES AND OTHER
THINGS.
I ALSO HAD A SUPER CREATIVE
YOUNG SCIENTIST WHO RECENTLY
JOINED MY LAB.
HIS BACKGROUND WAS COMPUTER
SCIENCE.
AND HE CONVINCED DR. RANSY AND I
TO HELP APPROACH A SUPER
COMPUTER AND PUT IT IN HIS HOME
SO HE CAN KEEP WORKING ON TRYING
TO SOLVE THIS MAJOR PROBLEM OF
GETTING THE PROTEINS TO DOCK.
IN DOING THIS WHAT HE WAS ABLE
TO DO WAS FEED OR CREATE MODELS
OF THE CONNEXOSOME PROTEINS MANY
OF WHICH HAVE BEEN PUBLISHED AND
TAKEN THE MUTANTS SCREENED IN
THE LAB AND CREATE AN ALGORITHM
TO WHERE HE CAN CONFIRM THE SAME
FOUR RESIDUES WE KNEW
PARTICIP
PARTICIPATED IN DOCKING AND CAN
SHOW THE PATTERNS TO CONTROL
DOCK.
HE FOUND THIS PATTERN WHICH
ESSENTIALLY WAS THREE NEGATIVE
RESIDUES AND A POSITIVE RESIDUE
ESSENTIALLY FORMING THE
CONNECTIONS CALLED SALT IMAGES
THROUGH THE POSITIVE RESIDUE ON
ONE SIGHT INTERACTING WITH THE
THREE NEGATIVE RESIDUES ON THE
OTHER CONNEXOSOME PROTEIN AND
FOUND THIS PATTERN IN 34.7.
THE SAME HE OBSERVED IN 35.
THROUGH A SERIES OF PROCESSES HE
ACTUALLY CAME UP WITH A STRATEGY
TO REGULATE HOW THESE
CONNEXOSOME PROTEINS WERE
DOCKED.
HERE'S THE ULTIMATE STRATEGY.
WE WOULD HAVE THREE POSITIVE
RESIDUES ON ONE SIDE, THREE
POSITIVE AND NEGATIVE ON ONE
SIDE AND ALL NEGATIVES ON THE
OTHER SIDE.
AND THROUGH THIS ITERATION OF
THE MODEL IN THE COMPUTER AND
TESTING IT IN OUR IN VITRO
SYSTEM HEK CELLS WE WERE ABLE TO
COME UP WITH THIS CUSTOM PAIR OF
CONNEXOSOME PROTEINS THAT DIDN'T
DOCK WITH THEMSELVES IN OUR IN
VITRO SCREEN BUT DID DOCK WITH
EACH OTHER WE WANTED TO TEST
THESE THIS PAIR IN VIVO NOW TO
SEE IF THEY COULD CHANGE THE
FUNCTION OF NEUROCIRCUITS.
IN ORDER TO DO THIS WE MADE SURE
FIRST THESE CONNEXOSOME PROTEINS
DIDN'T BIND WITH 43 AND 36.
THE ONES ENDOGENOUS TO THE PART
OF THE BRAIN.
WE REACHED OUT TO A COLLEGIATE
AT YALE AND AMONGST MANY THINGS
THAT DANIEL DOES, HE STUDIES C.
ELEGANS AND THEY WERE USEFUL FOR
SCREENING IN VIVO SYSTEM.
FIRST OF ALL C. ELEGANS IS
TRANSPARENT.
SECONDLY, THE NERVOUS SYSTEM IS
LARGELY BEEN MAPPED OUT 302
NEURONS AND EQUALLY IMPORTANT
THE NEURONS HAVE BEEN MAPPED ON
TO A SET OF BEHAVIORS.
FINALLY, IT'S A CLEAN SYSTEM
BECAUSE THEY'RE INVERTEBRATES SO
THEY DON'T HAVE CONNEXINS IN
THEM AND C. ELEGANS HAVE A SET
OF BEHAVIORS, ONE OF WHICH WE
CHOSE TO USE TO SCREEN OUR
PROTEINS.
NOW, C. ELEGANS THESE WORMS,
THIS BEHAVIOR THEY HAVE IS IF
YOU FEED THEM AT COLD
TEMPERATURES AND GIVE THEM A
CHANCE LIKE THE NEXT DAY TO
EXPLORE TEMPERATURE GRADIENT,
THEY'LL GO BACK TO THE SETTING
YOU FED THEM.
LIKE GRAD STUDENTS.
SO IF FEED THEM AT COLD
TEMPERATURES AND FEED THEM AT
WARM TEMPERATURES AND TEST THEM
THE NEXT DAY THEY'LL GO TO WARM
TEMPERATURES.
THIS BEHAVIOR IS CONTROLLED BY
TWO NEURONS A SENSORY NEURON
CALLED AFD AND INNER NEURON
CALLED AIY.
WHEN YOU FEED AT COLD
TEMPERATURES THE CONNECTION
BETWEEN THE TWO ARE WEAK AND
LOOKING AT CALCIUM IMAGING AND
SHOWING A BUNCH OF INDIVIDUAL C.
ELEGANS AND WE'RE RAMPING IT UP
FROM 18 DEGREES CELSIUS TO 22
AND AS YOU RAMP IT UP THE AFD
NEURON STARTS SHOWING INCREASED
CALCIUM SIGNAL.
THE POSTSYNAPTIC NEURON FED AT
COLD DOES NOT SHOW CHANGES
RELATED TO CALCIUM BECAUSE THE
CONNECTION BETWEEN THE TWO
NEURONS IS WEAK SO THERE'S NO
POSTSYNAPTIC CONNECTION IS WEAK
SO THEY GO TO WHERE IT'S COLD.
IF YOU FEED THE ANIMALS AT WARM
TEMPERATURES, NOW IF YOU LOOK AT
HOW THE POSTSYNAPTIC NEURON
RESPONDS THE AIY RESPONDS TO
TEMPERATURE INCREASES NOW THAT
NEURON STARTS SHOWING INCREASED
ACTIVITY AS A RESULT OF THE
TEMPERATURE INCREASE BECAUSE YOU
STRENGTHENED THE CONNECTION
BETWEEN THE TWO NEURONS AND IF
YOU ASK WHAT THE ANIMAL WILL
CHOOSE IF YOU PUT ON A
TEMPERATURE GRADIENT, NOW THE
ANIMALS MIGRATE TOWARDS WARM.
WE CAN EXPLOIT THE POSTSYNAPTIC
CHANGE AND THE TEMPERATURE
GRADIENT AS A REFLECTION OF HOW
STRONG THE CONNECTION IS BETWEEN
THE TWO CELLS, AFD AND AIY.
WE'LL SET UP AN EXPERIMENT WHERE
WE TAKE THE CONNECTIONS AND
EXPRESS THE CONNEXIN PROTEINS
AND WE'LL PUT THE LOCK IN THE
LOCK IN BOTH NEURONS, 34.7 IN
BOTH NEURONS AND YOU SEE NO POST
SYNAPTIC CALCIUM REVISE.
THIS IS WHAT WE EXPECT AT
BASELINE AND NEXT CASE WE PUT
THE KEY IN THE KEY, 35 AND 35
BETWEEN THEM AND AGAIN NO
POSTSYNAPTIC CLASS AND IT'S ONLY
IN THE CASE WHERE WE PUT THE
LOCK IN ONE NEURON AND KEY IN
THE OTHER NOW SUDDENLY YOU SEE A
POST SYNAPTIC CALCIUM RISE AS IF
WE'VE REWIRED THEM.
THIS IS WHAT THE ANIMALS LOOK
LIKE BEHAVIORALLY.
WHERE WE START WITH A WILD TYPE
ANIMALS THE WILD TYPE ANIMALS
MIGRATE TOWARDS COLD
TEMPERATURES.
THE ANIMALS WITH THE LOCK AND
THE LOCK MIGRATE TOWARDS COLD
TEMPERATURES AND THE KEY AND THE
KEY MIGRATE TOWARDS COLD
TEMPERATURES AS WELL.
IT'S ONLY IN THE CASE THAT WE
PUT THE LOCK AND THE KEY IN THAT
THE ANIMALS SUDDENLY MIGRATE
TOWARDS WARM TEMPERATURES AGAIN
AS IF WE REWIRED THE CONNECTION
BETWEEN THEM.
WE TESTED THEM AGAINST 43 AND 46
AND DON'T SEE A CALCIUM CHANGE
OR RISE.
WE SHOWED THESE WOULD WORK IN C.
ELEGANS AND IN THE LAST THREE OR
FOUR MINUTES I'LL WALK YOU
THROUGH OUR ATTEMPTS TO SEE IF
WE CAN GET THIS TO WORK IN A
MAMMAL.
SO WE'LL GO ALL THE WAY BACK TO
THE BEGINNING AGAIN.
WE'RE ESSENTIALLY LOOKING IN THE
ASSAY A STRESS-INDUCED
BEHAVIORAL CHANGE ASSAY AND WE
KNOW THAT IF WE PUT THE ANIMAL
IN THIS ASSAY TWO DAYS IN A ROW,
THE ANIMALS SHOW MORE IMMOBILITY
BETWEEN DAY ONE AND TWO.
WE MAP THIS BEHAVIOR ON TO TWO
CHANGES IN BRAIN AREAS IN THE
INFRALIMBIC CORTEX AND THE
THALAMUS USING CHANGES IN
RESPONDING AND RECORDED NEURAL
ACTIVITY AND USED THE BRAIN
WAVES TO FIND A PATTERN OF
INTERACTION AND FOUND A
SIGNATURE THAT CHANGED BETWEEN
DAY ONE AND DAY TWO.
WHEN WE DID THAT, WE WEREN'T
SURE WHETHER THE SIGNATURE
COMPENSATORY AND RECORDED AND
PLAYED THE INFORMATION INTO AN
ANIMAL'S BRAIN AND WHEN WE
LOOKED AT THE RESULT THE
SIGNATURE WAS COMPENSATORY AND
WHEN WE COULD ESSENTIALLY MAKE
THEM MORE RESILIENT TO THE
STRESS OUTCOME THAT WE WERE
MEASURING.
SO WHAT WE DECIDED TO DO IN THIS
CASE WAS TAKE OUR PROTEINS AND
PACKAGE THEM INTO VIRAL VECTORS.
THESE ADENO ASSOCIATED
EXPRESSIONS AND WAITED FOR IT TO
EXPRESS IN TRAFFIC AND PUT THE
KEY IN THE MEDIAL DORSAL
THALAMUS AND HERE'S THE
FLUORESCENT EXPRESSION AND THE
PROTEINS EXPRESSED IN THE
MAMMALIAN BRAIN AND WHAT
HAPPENED IF WE COULD PLAY THE
RESILIENCE ON TO THE ANIMALS
BRAIN AND WHEN WE LOOKED AT THE
NORMAL ANIMALS ON DAY ONE AND
TWO THEY SHOW INCREASED
IMMOBILITY ON THE FIRST DAY AND
SECOND DAY ON THE ASSAY.
FIRST I'LL SHOW YOU WHAT HAPPENS
IN THE EXAMPLE WHERE WE ARE
PUTTING THE LOCK AND THE LOCK IN
OR THE KEY AND THE KEY.
THE LOCK AND THE LOCK ARE
ANIMALS SHOWING CIRCLES AND KEY
IN THE KEY ANIMALS WITH Xs.
THEY'RE ALL PULLED TOGETHER
HERE.
YOU CAN SEE LIKE OUR NORMAL
ANIMALS, THESE ANIMALS SHOWED
INCREASE IMMOBILITY BETWEEN DAY
ONE AND DAY TWO.
THEY SHOW STANDARD ADAPTATION TO
THE STRESS EXPOSURE.
IT'S ONLY IN THE CASE WHERE WE
PUT THE LOCK AND THE KEY IN THAT
WE ESSENTIALLY CHANGE THE
BEHAVIORS OF THE ANIMALS SUCH
THEY NO LONGER SHOW THE STRESSED
INDUCED BEHAVIORAL ADAPTATION.
IN OTHER WORDS, THEY ACT AS IF
THE SAME WAY WE ACHIEVE THE
CLOSED LOOP STIMULATION DEVICE.
GENERALLY ONE WOULD PUT FUTURE
DIRECTIONS ON THE NEXT SLIDE.
I'LL SAY WE'VE BEEN SHARING
THESE TOOLS WITH A BUNCH OF
COLLEAGUES SO THEY CAN ALSO SEE
IF THEY CAN REWIRE AND EDIT THE
BRAIN CIRCUITS AND SEE IF THEY
CAN GET BEHAVIORAL CHANGES OUT.
THE CHALLENGES OF UNDERSTANDING
MENTAL ILLNESS ARE SO GREAT IT'S
GOING TO REQUIRE ALL OF US AS A
FIELD OF SCIENTISTS PROBING AND
SEEING IF WE CAN CHANGE THE
BRAIN CIRCUITRY.
I'LL TAKE TWO MINUTES OF LIBERTY
ON THE LAST SLIDE TO TELL YOU
BRIEFLY ABOUT THE INDIVIDUALS
THAT DID THE WORK.
THIS IS RANSY AND THE
POST-DOCTORAL RESEARCHER WHO
TOOK ON THE INCREDIBLE
CHALLENGE.
SHE'S A FIRST GENERATION COLLEGE
GRADUATE FIRST IN HER FAMILY TO
COME TO COLLEGE WHO TOOK ON THE
COLLEGE.
THEN RYAN BOWMAN WHO GREW UP IN
THE BAY AREA AND WENT TO
MONTESSORI SCHOOLS AND PART OF
THE DREAM TEAM AND CLEARLY
THINKS ABOUT SCIENCE DIFFERENTLY
AND BROUGHT INNOVATION TO THE
TASK AND A Ph.D. STUDENT IN MY
LAB MET HER AS AN UNDERGRAD AND
PLAYED A CRITICAL ROLE IN THE
EARLIER MUTANTS WE WERE
CREATING.
DALTON HUGHES PART OF THE
ORIGINAL DREAM TEAM IS AN M.D.
Ph.D. STUDENT AND TATTIANA
WORKED IN MY LAB AND ANOTHER
PLAYED AN CRITICAL ROLE IN THE
MOUSE BEHAVIORAL STUDIES
ORIGINALLY FROM IOWA AWARDED A
GRADUATE FELLOWSHIP.
STEVE LAGUE WHO HELPS RUN THE
WHOLE OPERATION DID HIS Ph.D. AT
PENN.
AND MY COLLABORATOR AT YALE A
PHENOMENAL SCIENTIST AND LEADER
WHO PLAYED A FUNDAMENTAL ROLE
BOTH IN HELPING ADVANCE THE
PROJECT AND THINKING MORE
BROADLY HOW TO BRING PEOPLE FROM
DIVERSE BACKGROUNDS INTO THE
SCIENCE.
ELI WILSON WHO IS NOW AT OREGON
IS A RISING SECOND YEAR M.D.
Ph.D. STUDENT WHO DID A
TREMENDOUS AMOUNT OF WORK ON THE
C. ELEGANS WORK AND HANNAH
SCHENNENSON NOW A SECOND YEAR
MEDICINE INTERN AT DUKE AND DID
MEDICAL SCHOOL AT PENN AND WILL
BE GRADUATING DEFENDING HER
Ph.D. THESIS ON MONDAY AND
PLAYED AN ORIGINAL ROLE IN THE
DREAM TEAM AND MOUSE
EXPERIENCES.
AND MY COLLABORATOR NANETTE
BROSACK AND THE BOY WONDER WHO
HAD THE SUPER COMPUTER IN HIS
HOME AND RAINBOW HMOLTMAN CREAT
THE MUTANTS THAT WE SCREENED
THANK YOU FOR OPPORTUNITY.
I HOPE THE WORK WILL ULTIMATELY
HAVE LEGS AS WE WORK TO REALLY
ESTABLISH IT IN MICE AND
ULTIMATELY THINKING HOW TO
TRANSLATE INTO MODIFYING HUMAN
NEUROCIRCUITS TO HELP COUNTLESS
PEOPLE WHO ARE SUFFERING.
SO THANK YOU.
>> GREAT, THANKS A LOT, KAF.
AMAZING TALK.
I HEARD KAF GIVE THIS TALK A
WEEK AGO AND IT'S JUST AS GOOD
IF NOT BETTER AND PAY ATTENTION
IN BIO CHEMISTRY CLASS.
YOU NEVER KNOW WHEN IT WILL SHOW
UP.
SO WE HAVE A WHOLE SLEW OF
QUESTIONS.
LET ME JUST START AND PLEASE
WE'LL TAKE THEM AS WE CAN.
THE FIRST ONE IS THE PERSON
WRITES IN I NOTICE THE BRAIN
MAPS FOR THE DEPRESSION STATE
WERE VERY UNIFORM LIKE SPOKES IN
A WHEEL AND VULNERABILITY IS
MORE RANDOM.
IS THERE ANY REASON WHY IT
CAUSES THE UNIFORM PATTERN?
>> IT'S INTERESTING.
THE APPEARANCE OF THE UNIFORMITY
IS BECAUSE THERE'S ESSENTIALLY
TWO FREQUENCIES THAT WE WERE
OBSERVING IN THE DEPRESSION
CASE.
SO WE WERE OBSERVING YOU CAN SEE
THE DATA FREQUENCY AND LOWER
FREQUENCY.
WHEN WE'RE THRESHOLDING AS THE A
SPREAD.
THE MAPS ACROSS ALL FREQUENCIES
ARE IN THE PAPER WE MENTIONED.
SO BOTH OF THEM HAVE
DISTRIBUTION ACROSS FREQUENCIES
AND THEY'RE JUST BROADER PEAKS
IN DEPRESSION.
>> I HAVE A RELATED QUESTION AND
THAT IS IT PERTAINS TO RECENT
CASE STUDIES FROM A GROUP IN
BAYLOR AND UCSF WHERE THEY'RE
DOING LONG-TERM RECORDINGS FOR
CERTAIN PATHWAYS IN THE BRAIN
AND CREATING STIMULATION
PARADIGMS FOR DEPRESSION.
AT SOME POINT THESE ROADS SHOULD
CROSS, RIGHT?
WHAT ARE YOUR THOUGHTS ON THAT?
>> THE HOPE IS THEY'LL
DEFINITELY CROSS.
WE WANT GENERALIZATION AND WANT
IT TO WORK IN A NEW PATIENT THAT
COMES IN THE DOOR.
THE QUESTION IS, HOW PRECISION
DOES PRECISION MEDICINE NEED TO
BE?
IF WE NEED SOMETHING PERFECTLY
DESIGNED FOR EACH PERSON THEN WE
HAVE A LONG WAY TO GO.
ON THE OTHER HAND, WE DON'T
THINK IT'S GOING TO BE TOTALLY
DISTINCT FOR EVERYBODY.
I ALWAYS LIKE TO USE THE EXAMPLE
OF AN E.K.G., AN ELECTROCARDIO
GRAM WE USE WHEN SOMEONE'S
HAVING CHEST PAIN.
THEY'RE NOT IDENTICAL FROM
SUBJECT TO SUBJECT.
EVERYBODY DOESN'T HAVE THE SAME
RESTING HEART RATE BUT WE KNOW
HOW TO MAKE SENSE OF THE
DIFFERENCES BECAUSE WE
UNDERSTAND THE PRINCIPLES SUCH
THAT WE KNOW HOW TO INTERVENE.
WHAT WE'RE INITIALLY LOOKING FOR
ARE E.K.G. LIKE SIGNATURES MOUSE
TO MOUSE AND IF WE CAN'T THE
THOUGHT WE'LL GET FROM MOUSE TO
HUMAN WILL BE TOO MUCH TO CROSS.
WE'LL OPERATE ON THE PRINCIPLE
THERE ARE THINGS CONSERVED
ACROSS SPECIES.
A MOUSE IS NOT A HUMAN BUT YOU
CAN UNDERSTAND THE HUMAN'S HEART
BY STUDYING THE MOUSE'S HEART
BECAUSE THERE'S SOME LEVEL OF
CONVERGENCE BETWEEN PATTERNS AND
WHAT IS CONVERGENT ACROSS
SPECIES BECAUSE IF WE CAN
DEVELOP A THERAPEUTIC, YES, SOME
THINGS WILL BE DIFFERENT FROM
SUBJECT TO SUBJECT BUT WE CAN
TARGET THE THING THAT IS
CONSERVED IN SUBJECTS BY
SUBJECTS.
>> AND GET BEYOND THE HANDFUL OF
STUDY WE CAN FIND COMMON
SIGNATURES AS WELL.
IT WILL BE EXCITING TO SEE HOW
THE ANIMAL AND HUMAN MODELS MY
TRANSLATE AND REVERSE TRANSLATE
AS WELL.
WE WON'T GET THROUGH ALL THE
QUESTIONS.
ARE YOU ABLE TO CONTROL THE
MODULATION PROCESS BY
CONNECTIONS?
IS THERE A WAY TO REVERSE THIS
AS WELL CONTROL THE EXTENT OF
NEUROMODULATION ?
>> IF YOU'RE A SCIENTIST PLEASE
JOIN THE STUDY SECTIONS BECAUSE
WHEN WE WRITE THE GRANT I HOPE
YOU'LL SIGN OFF ON THE
SIGNIFICANCE OF THE WORK.
AND OUR FIRST GOAL IS TO SHOW WE
CAN SELECTIVELY DEPLOY THESE AND
CHANGE THE FUNCTION OF BEHAVIOR
AND ULTIMATELY IF WE PUT THIS IN
HUMANS WE WANT A WAY OF EITHER
CONTROLLING WHEN THEY'RE
EXPRESSED AND NOT EXPRESSED TO
TURN ON AND OFF OR ENGINEERING
IN A SECOND SWITCH.
IT'S SORT OF ALMOST LIKE A
DESIGNER DRUG THAT TURNS THESE
SELECTIVE PROTEINS ON AND OFF SO
THE COMBINATION ALLOWS US TO
MODULATE IT IN THAT FRAMEWORK.
THAT FEATURE HASN'T BEEN BUILT
IN BUT SOMETHING WE'RE THINKING
ABOUT FOR FUTURE DIRECTION.
TO MY COLLEAGUE OUT THERE THAT
ASKED THE QUESTION, I HOPE YOU
UNDERSTAND THE SIGNIFICANCE OF
THAT IF YOU EVER SEE THAT.
>> SO NOT TO STRESS YOUR BIO
CHEMISTRY JOBS ANY FURTHER, MY
RECOLLECTION IS THE PERMEABILITY
CAN BE REGULATED.
>> IT CAN BE GATED.
THEY CAN BE GATED THROUGH
MELATONIN AND THROUGH CIRCADIAN
HOW OPEN AND CLOSED THEY ARE AND
THINGS WE CAN EXPLOIT THAT WOULD
ALLOW TO OPEN AND CLOSE THE
GATING OF THE CHANNELS.
>> LOTS OF GREAT STUFF YOU HAVE
TO DO.
AND ARE THERE ANY CHANGES
FOLLOWING CLOSED-LOOP
STIMULATION AND DO THEY PERSIST
OR STOP THE MOMENT YOU STOP
STIMULATING?
>> WE HAVE WIRES IN THE ANIMALS
AND WE CAN SEE THE PHYSIOLOGICAL
RESPONSE AND COME BACK AND
STIMULATE AGAIN AND THE BRAIN
RESPONDS DIFFERENTLY TO THE SAME
STIMULATION FROM DAY ONE.
THE BRAIN IS A LEARNING ENGINE
AND THE SAME WAY IT CAN LEARN
WITH FLASHING LIGHTS IN OR
HEARING SOUNDS, IT CAN LEARN BY
HAVING MASSIVE AMOUNTS OF
ELECTRICAL STIMULATION BEING
PRESENTED INTO THE BRIN.
SO THE BRAIN DOES ADAPT TO EVEN
ACUTE STIMULATION.
I HAVE NO DOUBT.
WE'VE BEEN DOING SOME
EXPERIMENTS.
SOME OF THE WORK IS LED BY A
POST-DOC IN MY LAB AL GROSSMAN
LOOKING AT CLOSED-LOOP AND
OPEN-LOOP STIMULATION OVER TIME
AND THE BRAIN ADAPTS DIFFERENTLY
TO THE OPEN-LOOP STIMULATION TO
THE CLOSED.
THE CLOSED CREATES A COINCIDENCE
IN THE BRAIN WE THINK IS
IMPORTANT FOR CREATING PLASTIC
CHANGES.
>> THAT'S ONE THING TO KEEP IN
MIND THE CIRCUITS IN THE BRAIN
ARE PLASTIC.
THIS IS SOMETHING WE NEED TO
KEEP TOP OF MIND.
>> WE SUSPECT WHEN WE PUT THE
PROTEINS IN AT A SYNAPTIC
INTERFACE THE BRAIN IS
ESSENTIALLY REACHING THE
HOMEOSTATIC STATE.
>> OKAY, SURE.
ENJOYING THE TALK.
THIS QUESTION CAME UP AT THE
MEETING WE WERE AT LAST WEEK.
LET ME STATE IT OUT LOUD HERE.
IS IT POSSIBLE YOU WORKED TO
TEST HOW ADDITIONAL LOAD TECH
INTERVENTION SUCH AS EXERCISE,
DIET, SOCIAL INTERACTIONS COULD
INTERACT WITH THESE MORE
INVASIVE AND NOVEL
INTERVENTIONS.
>> YEAH, SO THE SIMPLE ANSWER IS
YES.
PEOPLE HAVE LOOKED AT THINGS FOR
EXAMPLE LIKE IF ENRICHED
ENVIRONMENTS MAKE ANIMALS MORE
RESILIENT TO STRESSORS.
GENERALLY WHEN WE LOOK AT MICE
WE'RE LOOKING AT THEM IN HIGHLY
SANITIZED IMPOVERISHED
CONDITIONS THEY LIVE IN AND
HAVING A HIGHER RICH ENVIRONMENT
CAN HAVE AN INFLUENCE AND IT'S
POSSIBLE AND WE HAVE COLLEAGUES
FOCUSSING ON THIS EXTENSIVELY
LOOKING AT HOW THE BRAIN IS
MODIFIED IN RESPONSE TO THOSE
ENVIRONMENTAL BUFFERING
EXPERIENCES.
IT'S THE CASE WITH HUMANS AS
WELL.
WE KNOW -- AS A CLINICIAN I
ALWAYS ENCOURAGE DIET AND
EXERCISE AS A KEY PART OF
BUILDING HUMAN RESILIENCE AS
WELL.
SO THERE'S CERTAINLY PLATFORMS
IN WHICH WE CAN FIND THE HIGHER
TEM MANIPULATIONS AND LOWER TECH
MANIPULATIONS IN THE SAME
SUBJECT AND SEE HOW THEY
INTERACT.
IF YOU LOOK AT SOMETHING LIKE
CANCER, WE CERTAINLY ENCOURAGE
DIET AND SMOKING CESSATION AND
EXERCISE AND THERAPEUTICS TO ALL
WORK TOGETHER IN THE BODY.
>> COOL.
I'M GOING TO SKIP DOWN TO ONE OF
THE LATE-BREAKING QUESTIONS AND
FOLD IT INTO A MORE GENERAL ONE.
SO AS WE THINK AHEAD, HOPEFULLY
NOT TOO FAR AHEAD OF DEPLOYING
PRECISION GENE THERAPIES FOR
REGULATING CIRCUIT DISORDER
WE'RE LIMITED.
FIRST, WE NEED TO BE ABLE TO
TARGET CELLS PRECISELY WE THINK
ARE INVOLVED IN VARIOUS
DISORDERS WHETHER IT'S A
MOVEMENT, EPILEPSY OR AS WE'RE
TALKING ABOUT HERE, MOOD
DISORDERS.
THAT'S ONE CHALLENGE AND WE'RE
WORKING ON SOLUTIONS FOR
DELIVERY AND SPECIFICITY THERE.
THEN ONCE IF YOU FIGURE OUT
WHICH CELLS YOU WANT TO TARGET
AND MODULATE YOU NEED A WAY OF
MODULATING.
ONE WAY IS THROUGH THE GAP
JUNCTION TECHNIQUE YOU'VE
DESCRIBED ELEGANTLY AND THE
OTHER IS OPTOGENETICS AND THAT'S
OUT THERE BUT THAT REQUIRES
STICKING SOMEBODY IN OR ON
SOMEBODY'S HEAD TO STIMULATE.
SO HOW DO YOU THINK AT THE END
OF THE DAY OR IN THE NEAR
FUTURE, I SHOULD SAY, IN THE
NEAR FUTURE, HOW DO YOU SEE
OPTIMAL DEPLOYMENTS WITH THE
CONNECTIONS AND WHAT WILL BE THE
PLUSES AND MINUSES HERE?
>> FIRST, LET ME SAY, THESE ARE
HUGE CHALLENGES THAT ARE GOING
TO REQUIRE MAJOR WORK ON THE
PART OF THE FIELD.
I JUST HAPPEN TO -- AS A COUNTRY
WE HAVE GONE AND PUT HUMANS ON
THE MOON AND WE'RE ON OUR WAY TO
MARS.
SO WITH ENOUGH FOCUSSED
INTENTION ON THE PART OF A BROAD
GROUP OF SCIENTISTS OUT THERE
WORKING REALLY HARD WITH THE
APPROPRIATE LEVEL OF SUPPORT,
THIS IS SOMETHING WE CAN PULL
OFF AND I WOULD SIMPLY ARGUE
LOOKING AT MENTAL CHALLENGES AN
DISEASES LIKE ALZHEIMER'S ARE
JUST AS IMPORTANT IF NOT MORE
IMPORTANT THAN PUTTING HUMAN
BEINGS ON THE MOON.
SO THIS IS A MAJOR CHALLENGE BUT
WE HAVE TO WORK ON DEVELOPING
TOOLS LIKE PRECISION TOOLS
ACROSS THE BLOOD BRAIN BARRIER
AND NEED THE HUMAN CELL ATLAS
AND THE WORK IS BEGINNING AND
UNDERWAY.
I SAY THIS IN THE FRAMEWORK THAT
I NEED -- WE AS A FIELD TO COME
THROUGH FROM THESE THINGS IN
ORDER FOR THE TECHNOLOGY TO
ULTIMATELY BE DEPLOYED.
WITH THAT SAID, I DO THINK
THERE'S ANOTHER POTENTIAL TOOL
EARLIER IN ITS DEVELOPMENT IN
WHICH IF WE CAN GET IT TO
SPECIFIC BRAIN CELLS WHAT I LIKE
ABOUT THE CON EXIN TOOL WE'RE
TARGETING TO BRAIN CELL TYPE
INTERACTIONS.
WE GET A LEVEL OF SPECIFICITY
THERE NOT JUST TURNING OFF OR ON
THE SOUND, WE'RE CONTROLLING THE
INTERFACE BETWEEN THE CELLS AND
CONTROLLING IT IN A WAY THAT
LEAVES THE CONTROL OF THE SECOND
CELL STILL UNDER THE PARAMETERS
OF THE FIRST CELL.
SO HERE IT IS THE FIRST CELL
THAT IS CONTROLLING THE SECOND
CELL MEANING WE STILL STAY UNDER
THE CONTEXT OF CONTROLLING THE
BRAIN.
IT WILL BE IMPORTANT FOR
TARGETING SPECIFIC BEHAVIORS
WHILE LEAVING OTHER BEHAVIORS
IN.
ULTIMATELY, AS I MENTIONED, IT
REQUIRES WORK BY THE FIELD MORE
BROADLY.
>> THAT'S A GREAT POINT BECAUSE
CERTAINLY IT'S NOT JUST ENOUGH
TO STIMULATE THE PRESYNAPTIC
CELL BUT THAT WILL MAKE A
VARIETY OF CONNECTIONS INCLUDING
WITH BOTH OTHER EXCITATORY AND
INHIBITORY NEURONS AND IF YOU
CAN NEURO DOWN THE PATHWAY IT
WOULD BE A HUGE BENEFIT.
THE MORE TOOLS IN THE TOOLBOX
THE BETTER OFF WE'LL BE AND IT
IS A HUGE CHALLENGE.
I THINK WE CAN GET THERE WITH
THE TOOLS WE'RE BUILDING WITH
OUR PROJECTS.
WE HAVE TIME FOR ONE OR TWO
MORE.
>> WE NEED SUPPORT FROM THE
COMMUNITY AND FROM CONGRESS TO
GET THERE.
>> RIGHT.
>> THE MAP WE CREATED FOR
DEPRESSION STUDIES WERE IN
MALES.
WE SINCE FOLLOWED THAT UP WITH
WORK FROM A GRADUATE STUDENTS
LOOKING FOR MAPS IN FEMALES AND
SEEING THE EXTENT TO WHICH THEY
GENERALIZE.
THE GENE EXPRESSION PATTERNS
RELATED TO STRESS-INDUCED
BEHAVIORS ARE DIFFERENT.
THEY DON'T LOOK IDENTICAL
BETWEEN MALES AND FEMALE MICE.
AS WE KNOW, ILLNESS LIKE
DEPRESSION AND ANXIETY ARE MORE
PREVALENT IN FEMALES THAN MALES.
WE'RE HOPING THE LEVEL OF
CONVERGENCE BETWEEN SEXES WILL
COME UP IN THE FRAMEWORK AND
THEN COME UP WITH THE
DIFFERENCES BETWEEN SEXES.
>> THERE'S A WHOLE SLEW OF
QUESTIONS STILL.
I APOLOGIZE WE WON'T GET TO
THEM.
WE'RE RUNNING A BIT OVER TIME
BUT THANK YOU AGAIN, KAF, FOR A
TERRIFIC TALK AND STIMULATE AND
PROVOCATIVE.
I LOOK FORWARD TO SEEING THE
NEXT SET OF EXPERIMENTS AND
HOPEFULLY WILL START SPREADING
INTO OTHER PEOPLE'S HANDS AS
WELL.
OKAY, SORRY I DIDN'T GET TO ALL
THE QUESTIONS.
YOU CAN PROBABLY FIND KAF AND
ASK HIM DIRECTLY AND TOO BAD
WE'RE NOT IN PERSON IN THE
MEETING BUT HE CAN BE FOUND
ELECTRONICALLY.
I WANT TO MOVE TO OUR NEXT PHASE
THAT'S TO ANNOUNCE THE WINNERS
OF THE BRAIN INITIATIVE SHOW US
YOUR BRAINS PHOTO AND VIDEO
CONTEST.
THIS IS ALWAYS A REAL FUN PART
OF THE MEETING FOR ME TO SEE IN
ADDITION TO THE SCIENTIFIC
CREATIVITY OR TO COMPLEMENT THE
SCIENTIFIC CREATIVITY FOR OUR
COMMUNITY, LET'S SEE THE
ARTESTRY THAT COMES FROM THIS.
THIS YEAR WE HAD A BUNCH OF
ENTRIES AND NARROWED IT DOWN TO
VIDEOS AND PHOTOS.
THE CONTEST ATTRACTED MORE THAN
2,000 PAGE VIEWS DURING THE
PUBLIC VOTING WITH MORE THAN 300
VOTES FOR EACH ENTRY.
I'D LIKE TO ANNOUNCE THE TOP
THREE PHOTOS AND VIDEOS OF THE
2022 CONTEST.
AND THERE'S MEMORY FROM
STEPHANIE GRELLO FROM BOSTON
UNIVERSITY.
A GORGEOUS PHOTO HERE SHOWING
TWO MEMORIES UNDER THE
MICROSCOPE INTO THE HIPPOCAMPUS
OF A MOUSE USING VIRAL
TECHNOLOGY AND OPTOGENETICS.
THE SECOND IS ENTITLED MIND MAP
THE INTRICATE WIRING OF THE
HUMAN MIND.
THEY'RE FROM THE UNIVERSITY OF
NORTH CAROLINA CHAPEL HILL.
THEY'RE VISUALIZING THE BRAIN
ACTIVITY AND PROPAGATING BRAIN
INFORMATION TO FIBER TRACKS AND
LOOKING AT DIFFUSION TOPOGRAPHY.
THE NEXT IS AND LOOK AT THIS AND
SORRY ABOUT MY PRONUNCIATION.
IF YOU LOOK AT THIS, YOU CAN SEE
AND YOU CAN IMAGINE ABRAHAM
LINCOLN'S PROFILE AND THIS IS
STAINED.
THE NEXT ONE IS THE FIRST PLACE
VIDEO IS FROM ANDREAS SHOWING
TWO PHOTON IMAGING WITH MATCHING
MORPHOLOGIES.
HERE PUTTING TOGETHER THE
MODALITIES.
THE SECOND PLACE VIDEO AND
TRANSFORMING INTRACRANIAL
RECORDING OF AN ONGOING SEIZURE
USING RECONSTRUCTION OF THE
PATIENT'S OWN BRAIN.
AND IS A RENDERING OF
RECONSTRUCTION OF LAYER FIVE
CORTICO IONS.
IS IT BLINKING?
I WANT TO CONGRATULATE ALL THE
WINNERS AND THANK THE
CONTESTANTS.
WE LOOK FORWARD TO SHOWCASING
THE WORK ON THE WEBSITE.
I THINK IT'S GOING UP AS WE
SPEAK.
I ENCOURAGE EVERYBODY TO CHECK
OUT THE POSTERS AND PLEASE STAY
TUNED FOR THE TRAINEE HIGHLIGHT
AWARDS IN THE AFTERNOON
HELLO, I'M JOHN, WE
HAVE POST DOCS WE RECEIVED
SUBMISSIONS AND THE REVIEWS IN
THE 2021 CLIMATE COMMITTEE
SELECT THE 30 TOP FINALISTS TO
PRESENT FLASH TALKS ALONG WITH
AN INTERACTIVE VIRTUAL POSTER
AND HONORABLE RECIPIENTS WILL
EXPLAIN IN THE POSTER GALA.
>>MORE HOW THE AMAZING
RESEARCHERS WERE SELECTED.
WE JUDGED THE SCIENTIFIC
EFFORTS, THE RESEARCH
DISCOVERIES OF HIGH RELEVANCE
WITH PRIORITIZATION OF DATA AND
PLANS AS PROMOTE.
THE SECOND THING WE LOOKED AT
WAS HOW THE TRAINEE'S RESEARCH
CONTRIBUTES TO THE LARGER
BRAIN-RELATED RESEARCH EFFORT.
THE LAB AND/OR THE OVER ALL
PROJECT GRANT.
FINALLY, SOMETHING REALLY
IMPORTANT FOR THE BRAIN
INITIATIVE, INCLUSION.
INCLUSION AND STRATEGIES
UTILIZED TO ADVANCE THE
SCIENTIFIC AND TECHNICAL MERIT
OF THE PROPOSED PROJECT THROUGH
EXPANDED INCLUSIVITY.
WE'LL GET STARTED SOON BY
LISTENING TO THESE FOUR-MINUTE
TALKS KEEP IN MIND YOU CAN
SUBMIT QUESTIONS IN THE Q&A BOX
YOU SEE TO PRESENTERS AS THE
TALKS ARE GOING.
.
PLEASE NOTE THE NAME OF THE
PRESENTER.
THIS WILL HELP US WHEN WE GO TO
THAT PORTION OF THE MEETING.
WE'LL BE LEADING HE DISCUSSION
SESSION WITH OUR IMPRESSIVE
TRAINEES AFTER THE VIEWING OF
ALL THE PRESENTATIONS.
SO JOIN US IN WELCOMING OUR
TRAINEE HIGHLIGHT AWARD
PRESENTERS.
>> I'M A POST-DOCTORAL
RESEARCHER AT THE COLLEGE OF
MEDICINE CENTRAL MICHIGAN
UNIVERSITY.
I APPRECIATE THE OPPORTUNITY AND
PLATFORM TO SHARE MY RESEARCH
AND WE DEVELOPED A TOOL NO BIO
LUMINESCENCE.
IT MEANS BIO LUMINESCENT LIGHT.
HERE BETWEEN THE CELLS.
WHEN THE CENTER IS A PRESYNAPTIC
AND THE RECEIVER IS A POST
SYNAPSE.
BIO LUMINESCENCE IMITAIMITATES.
THE PRESYNAPTIC NEURON TARGETS
THE VESICLES AND IN THE PRESENCE
OF A SMALL MOLECULE THE
SUBSTRATE FOR THIS EN GAME, BIO
LUMINESCENT LIGHT IS EMITTED.
THE LIGHT ACTIVATES THE
OPTOGENETIC ELEMENT EXPRESSED IN
THE POST SYNAPTIC NEURONS.
WE CAN FIND THE EFFECT BASED ON
THIS MODULATION AND WE USE A
HYPER POLARIZING ELEMENT.
A TOOL THAT FORMS SYNAPTIC
TRANSMISSION BETWEEN SPECIFIC
PARTNERS, FOR EXAMPLE, BY
ENHANCING OR SUPPRESSING
TRANSMISSION OF THESE PATTERNS
WILL BE CRITICAL FOR INSIGHTS
INTO FUNCTIONING.
IT IS ALSO A PROSPECTIVE
STRATEGY TO LOOK AT
INTRACELLULAR COMMUNICATION
UNDER VARIOUS CONDITIONS.
PERTURBATIONS IN INTRACELLULAR
CONVERSATION THAT IS NEURONAL
CONVERSATIONS BEING TOO LOUD OR
TOO QUIET IS A LIKELY CAUSE OF
NUMEROUS NEUROPSYCHIATRIC
DISEASES.
ALSO, WHILE WE'RE CARRYING THIS
OUT IT CAN BE EXTEND FROM NEURON
TO MUSCLE OR TO CELL TO CELL
COMMUNICATION.
I HOPE YOU'LL GET A CHANCE TO
CHECK OUT THE POSTER ON THIS
TOPIC FOR MORE INSIGHTS INTO BIO
LUMINESCENCE.
I'D WELCOME YOUR KIND FEEDBACK
AND INQUIRIES AND COMMENTS.
>> I'M A POST-DOCTORAL FELLOW AT
BAYLOR COLLEGE OF MEDICINE IN
HOUSTON, TEXAS.
I IDENTIFY NEURAL SIGNATURES
RELATED TO OCD OR OFFENSIVE
COMPULSIVE DISORDER.
THERE'S NO CURRENTLY NO
SIGNATURES OF THE CD SYMPTOMS
STATES AND THIS MAY BE DUE TO
LIMITED ACTIVITIES FOR
INTRAPHYSIOLOGICAL REPORTINGS
WHERE THE NATURAL ENVIRONMENTS
THEY'RE TAKING PLACE.
DEEP BRAIN STIMULATION OR DBS
PLATFORMS OFFER A WAY OVER THE
HURDLE ALLOWING FOR A TIME
DOMAIN STREAMING OF LFPs AT
HOME.
ANALYSIS OF THESE RECORDINGS MAY
A BETTER PATH TOWARD NEUROMARKER
IDENTIFICATION AND OCD.
HERE'S PART OF A CLINICAL TRIAL
FOR OCD AND HUMAN PARTICIPANTS
WITH OFFENSIVE COMPULSIVE
DISORDER WERE RECORDED WITH DBS
DEVICES AND WE LOOKED AT DISEASE
SPECIFIC BEHAVIORS CAPTURING
OVER 1,000 HOURS OF NEURAL DATA
IN FIVE PARTICIPANTS BOTH IN THE
CLINIC AND AT HOME.
THE DATA WAS COLLECTED OVER THE
COURSE OF THREE DAYS BY A SINGLE
PARTICIPANT.
THIS PARTICIPANT LOGGED THEIR
OCD SYSTEM INTENSITY FREQUENTLY
DURING THE COURSE OF THE
THREE-DAY PERIOD AND ENCOUNTERED
TRIGGERS ON DAY ONE AND TWO.
THE WIDE RANGE OF SEVERITY OVER
WHICH THE DATA WAS CAPTURED
ALLOWED US TO LOOK AT SYMPTOM
INTENSITY.
USING THE VENTRAL DATA CAPTURED
AROUND EACH INTENSITY RATING I
COMPETED SPECTRAL POWER IN FIVE
INTERESTS BETA, ALPHA AND GAMMA
BANDS AND FOUND A STRONG
NEGATIVE CORRELATION IN DELTA
BAND POWER.
WE CONSIDER THIS DELTA BAND
SIGNAL TO BE A CANDIDATE
BIOMARKER OF OCD STRESS AND
THINK IT CAN DEMONSTRATE OCD AND
DEMONSTRATE THE FEASIBILITY OF
CAPTURING PHYSIOLOGY TO ENABLE
NEURAL BIOMEDICAL
IDENTIFICATION.
A PREREQUISITE FOR ADAPTIVE DBS
FOR OCD AND OTHER DISORDER.
>> MY NAME IS JAY GILL.
I'M AN M.D. Ph.D. STUDENT AT
UCLA CURRENTLY COMPLETING THE
THIRD YEAR OF MY PH.D.
I'M COMPLETING MY PROJECT UNDER
DOCTOR LANGEVINS.
THE NEURAL PHYSIOLOGICAL
MECHANISMS IN THE HUMAN AMYGDALA
THAT UNDER LIE POSTTRAUMATIC
STRESS DISORDER ARE POORLY
UNDERSTAND.
IN THE FIRST OF ITS KIND STUDY
WE RECORDED DATA IN TWO
INDIVIDUAL WITH AMYGDALA
ELECTRODES FOR
TREATMENT-RESISTANT PTSD AND SO
WE'RE ABLE TO IMPLEMENT
CLOSED-LOOP NEUROSTIFF USING THE
RNS.
HOW THIS WORKS IS IT'S IMPLANTED
IN THE ELECTRODES ARE ABLE TO
STIM AND ALSO LISTEN.
SO SPECIFICALLY, THE RNS SYSTEM
LISTENS TO CHANGES IN POTENTIAL
OSCILLATIONS WHICH REFLECT THE
POPULATION RESPONSES OF A REGION
IN THE BRAIN AND SO IT TAKES THE
ACTIVITY IT'S LISTENING TO AND
LOOKS FOR A PROGRAM ASSOCIATED
WITH THE PATHOLOGY OF THE
DISORDER.
SO ONCE THAT SIGNAL IS HEARD,
THE DEVICE DELIVERS STIMULATION.
IN THIS WAY, IT CLOSES THE LOOP
THAT IS CREATED BETWEEN THE
BRAIN'S ACTIVITY AND THE THERAPY
DELIVERED.
SO ONE OF THE CHALLENGES FOR
THIS NOVEL STUDY THAT WE'RE
COMPLETING IS THAT WE DO NOT
KNOW WHAT THE SIGNAL THAT THE
DEVICE SHOULD BE LISTENING TO.
SO WHAT IS THE
ELECTROPHYSIOLOGICAL REFLECTION
OF THE PATIENT SYMPTOMS.
SO THE WORK THAT I'VE DONE
THROUGHOUT MY Ph.D. HAS BEEN
TRYING TO DEFINE THESE NOOIR
PHYSIOLOGICAL BIOMARKERS OF PTSD
SPECIFIC SYMPTOMS AND AND IN
ORDER TO FIGURE OUT WHAT OUR
BRAIN ACTIVITY CHANGES THAT
RELATE TO FEATURES OF PTSD WE
HAD TWO INDIVIDUALS PERFORM A
BATTERY OF TESTS THAT EXPOSED
THEM TO EXPERIENCES AND ACROSS
ALL PARADIGMS AND AN EXPOSURE
TASK WHERE SUBJECTS LISTEN TO
AUDIO SCRIPTS OF THEIR
INDIVIDUAL TRAUMAS AND A TASK IN
ALL THOSE WE FOUND THAT THERE'S
ELEVATION IN 5 TO 9 HERTZ POWER
IN THE CONDITIONS AND THIS MAY
BE A REFLECTION OF THE BRAIN
PROCESSING A NEGATIVE STIMULUS.
SO WE BELIEVE THIS WILL BE VERY
HELPFUL IN TRIGGERING
STIMULATION.
WHILE MY WORK WILL LARGELY FOCUS
ON TALKING ABOUT THE BIOMARKER
DEFINITION, IF YOU'RE INTERESTED
IN SEEING HOW OUR PATIENTS HAVE
FEARED WITH THE CLOSED-LOOP
MODULATION I ENCOURAGE YOU TO
VISIT THE TALK OF MY MENTOR.
THANKS FOR LISTENING.
>> HELLO, EVERYONE.
MY NAME IS SANDRA CHAN.
I'M A Ph.D. CANDIDATE AT PENN
STATE.
I'M HERE REPRESENTING MY
RESEARCH TEAM AND SHARING
FINDINGS WITH YOU.
I'LL START WITH GIVING YOU
CONTEXT ABOUT THE PROJECT.
THE MENTAL DISORDER PREVALENT IN
THE U.S. AND WORLDWIDE USUALLY
PSYCHOLOGICAL AND PHARMACOLOGIC
TREATMENTS ARE INTERVENTIONS FOR
FIRST LINE DEPRESSION YET MOST
DO NOT RESPOND WELL TO PSYCHO
THERAPY.
AND INTERVENTIONS DELIVER PULSES
TO THE BRAIN CAN TREAT
PSYCHIATRIC CONDITIONS INCLUDING
DEPRESSION.
HOWEVER, STUDIES LOOKING AT
PATIENTS AND PUBLIC ATTITUDES
ACROSS THIS HAVE BEEN LACK.
IN THE PROJECT WE FOCUS ON FOUR
TECHNOLOGIES.
ELECTROCONVULSIVE STRATEGY AND
USED TO TREAT DEPRESSION AND
DEEP BRAIN STIMULATION AND
ADAPTIVE BRAIN IMPLANTS WHICH
ARE ON CLINICAL TRIAL.
IT'S IMPORTANT TO EXAMINE
ATTITUDES TOWARDS THE
TECHNOLOGIES FOR TWO REASONS.
FIRST, HAVING AN ACCURATE
UNDERSTANDING OF THE
STAKEHOLDERS VIEW WILL HELP
PROFESSIONALS MAKE TREATMENT
ACCOMMODATIONS.
TO THAT END OVER THE COURSE OF
FOUR YEARS THEY INTERVIEWED AND
CONDUCTED A NATIONAL SURVEY THAT
INCLUDES PSYCHIATRISTS, PATIENTS
AND MEMBERS OF THE GENERAL
PUBLIC.
THEY CAREFULLY IDENTIFIED THE
ETHICAL CONCERNS AND VIEWS THE
STAKEHOLDERS HAVE ABOUT THE
NEWER TECHNOLOGIES AND
CONTRIBUTIONS OF A MAP THAT WILL
ALLOW US TO INVESTIGATE THE
SOCIAL MEANING ATTACHED TO THE
NEWER TECHNOLOGIES AND
UNDERSTAND PERCEPTIONS AROUND
THEM.
TO CREATE THE MAP WE DREW ON
QUANTITATIVE AND QUALITATIVE
DATA AND THE LITERATURE ON THE
OTHER.
AND WE WANTED THE MAP TO HELP US
ANTICIPATE THE ETHICAL
CHALLENGES P.I.s RAISED AS WELL
AS A SOCIAL GUIDANCE IN THE
DEVELOPMENT.
IN THE PROCESS OF CREATING THESE
MAPS WE LEARNED SIGNAL LINK AND
IT'S INTEGRAL FOR STAKEHOLDERS'
VIEWS ABOUT USING THEM TO TREAT
DEPRESSION.
STIGMA INFLUENCES DEPRESSION
SHAPING HOW RISK OR BENEFICIAL
THEY APPEAR TO BE, HOW INVASIVE
THEY'RE CONSIDERED AND HOW MUCH
THEY CAN CREATE A PERSON'S SENSE
OF SELF.
THOUGH TREATMENTS FOR DEPRESSION
ARE STIGMATIZED TO VARYING
DEGREES THE STIGMA HAS TO BE
SEPARATED FROM THE STIGMA OF
DEPRESSION THOUGH IN PRACTICE
THEY'RE INTERRELATED.
WE HOPE THE MAP INCREASES
AWARENESS OF HOW STIGMA
FUNCTIONS AS A COMPLEX BARRIER.
AND IMPLEMENTATION OF P.I.s FOR
DEPRESSION WHILE IT HAS BEEN OUR
UNDERSTANDING HOW STILL MA
RELATE -- STIGMA RELATED AND
ACTS WITH DEPRESSION ITSELF.
STIGMA DISTORTS THE VISION.
WE KNOW MENTAL HEALTH STIGMA
TENDS TO DOWN PLAY THE SEVERITY
OF DEPRESSION, THE STIGMA SKEWS
THE CHARACTERISTICS AND ACCESS
TO WHAT ARE SAFE AND EFFECTIVE
INTERVENTIONS FOR DEPRESSION.
THANK YOU.
>> I'M A GRAD STUDENT IN THE LAB
AT CAL TECH.
TODAY I WANT TO TALK TO YOU
ABOUT OUR EFFORTS TO DESIGN A
VIRAL PLATFORM THAT DELIVERS
GENES TO THE BRAIN.
WHY DOES IT MATTER?
ONE OF THE GOALS OF THE BRAIN
INITIATIVE IS TO ENABLE WHOLE
BRAIN IMAGING OF ACTIVITY OVER
LONG PERIOD OF TIME AND AS MANY
IN THE AUDIENCE PROBABLY KNOW,
COMMONLY USED TECHNIQUES WHILE
THEY OFFER HIGH RESOLUTION LACK
PENETRATION DEPTH.
IN CONTRAST, ULTRASOUND IS A
MEDICAL TECHNOLOGY THAT OFFERS A
PENETRATION WITHOUT COMPENSATING
THE RESOLUTION.
UNTIL RECENTLY, ULTRASOUND
IMAGING HAS BEEN LIMITED TO
IMAGING.
IN THE LAST YEARS OUR LAB AND
OTHERS HAVE ENGINEERED DERIVED
NANO STRUCTURES OF PROTEINS AND
THE USE HAS BEEN LIMITED TO CELL
CULTURE.
DUE TO THE FACT THAT THE
EXPRESSION OF REQUIRES
CO-EXPRESSION OF MORE THAN
EIGHT.
HERE IN THE WORK I DEVELOPED A
MODULAR DELIVERY PLATFORM THAT
EFFICIENTLY DELIVERS GENES INTO
MAMMALIAN CELLS AND TISSUES.
THE VIRAL VECTOR ARCHITECTURE
PRODUCES STRONG ULTRASOUND
CONTRAST.
WE THEN DEMONSTRATE THE VECTORS
CAN BE USED TO RECORD ACTIVITY
BY PLACING THE EXPRESSION OF
GASES UNDER THE CONTROL OF THE
PROMOTERS SUCH AS CFAS.
WHAT I AM MOST EXCITED ABOUT IS
WE CAN EVEN IMAGE GREEN
EXPRESSION IN THE MOUSE BRAIN
AFTER INTRACRANIAL INJECTION
WHICH IS THE FIRST TIME WE COULD
DESCRIBE ULTRASOUND COULD BE
USED TO IMAGE EXPRESSION IN A
LIVE ANIMAL.
HERE ON THE SLIDE THE HEAT MAP
IS SHOWING THE GENE EXPRESSION
OF CELLS IN THE BRAIN THAT ARE
EXPRESSING OVERLAID ON TOP OF
THE FUNCTIONAL ULTRASOUND IN
GRAY SCALE TO GIVE YOU AN IDEA
OF THE ANATOMY OF THE BRAIN.
AND IN THE BOTTOM IMAGE YOU'RE
LOOKING AT THE CORRESPONDING
HISTOLOGY AFTER THE MOUSE HAD
BEEN SACRIFICED.
THE NEXT STEP FOR THE PROJECT IS
TO NOW INTEGRATE OUR IMMEDIATE
INTERFACE ACTIVITY SENSORS TO
LOOK AT ACTIVITY IN RESPONSE TO
STIMULI IN A MOUSE.
AND WE'RE HOPING TO ENABLE
IMAGING OF GENE EXPRESSION IN
THE SAME ANIMAL OVER LONG PERIOD
OF TIME.
IF YOU'RE INTERESTED IN HEARING
MORE ABOUT THE WORK OR HAVE
IDEAS WHAT WE CAN USE THE TOOL
KIT FOR ATTEND MY POSTER 836 IN
THE MONITORING NEURAL ACTIVITY
SECTION.
THANK YOU.
>> HI, EVERYONE.
I'M ETHAN ROY A THIRD YEAR Ph.D.
STUDENT AT THE STANFORD
UNIVERSITY GRADUATE SCHOOL OF
EDUCATION.
I'M EXPLORING WHITE MATTER
PROPERTIES.
STUDIES USING CROSS SECTIONAL
AND LONGITUDINAL METHODS HAVE
SHOWN THE CORE WHITE MATTER
COMPONENTS OF THE READING
CIRCUITRY.
THEY CAN LEAD TO CONFLICTING
CONCLUSIONS.
WE LEVERAGED LARGE SCALE DATA
SETS TO TEST TWO HYPOTHESES
SURROUNDING THE RELATIONSHIP
BETWEEN WHITE MATTER AND SCALE.
A, WHITE MATTER PROPERTIES
REFLECT STATIC BRAIN ORDER
S RELATED TO READING SKILLS.
GAINS IN READING SKILL
CORRESPOND TO CHANGES IN WHITE
MATTER ORDER
IN THE LEFT SIDE.
AND WE LOOKED AT THE HPD DATA
SET SETS AND FOUND COMPARISONS
NOR HIGH DIMENSIONAL PROPERTIES
SUGGEST LONGITUDINAL WITHIN
SUBJECT BETTER SUIT FOR
UNDERSTANDING THE LINK BETWEEN
WHITE MATTER READING SKILL AND
AN INDIVIDUAL'S ACADEMIC
ENVIRONMENT AND PAST FINDINGS
FROM SINGLE OBSERVATION STUDIES
MAY NOT NECESSARILY GENERALIZE
THE LARGE DIVERSE SAMPLES.
THESE FINDINGS WILL EXPLORE THE
LONGITUDINAL RELATIONSHIP
BETWEEN READING AND WHITE MATTER
DEVELOPMENT AND POTENTIALLY
CONTRIBUTE TO NEUROSCIENCE
INFORMED READING INTERVENTIONS.
I HOPE YOU GET A CHANCE TO STOP
MY BY POSTER AND LOOK FORWARD TO
VIRTUALLY MEETING YOU.
>> HI, I'M CURRENTLY A Ph.D.
STUDENT AT THE UNIVERSITY OF
MINNESOTA.
I'M GOING GO OVER HOW WE'RE
GOING TO MODEL THE ELECTRODES IN
THE BRAIN BY MAGNETIC
STIMULATION TO ADDRESS THE
BOTTLENECK IN RESEARCH IN
LIMITED RESEARCH IN CERTAIN
CLINICAL SETTINGS.
TMS IS A PROMISING MODULATION
THAT IS SAFE AND CAN TARGET
REGIONS IN THE BRAIN.
TMS HAS BEEN APPROVED FOR
PSYCHIATRIC DISORDERS SUCH AS
DEPRESSION AND OCD.
IT HAS THE HIGHEST CHANCE OF
SUCCESS WHEN THE PROTOCOL IS
DESIGNED AND OPTIMIZED FOR EACH
INDIVIDUAL AND CAN DEVELOP THESE
WITH THE ASSISTANCE OF
COMPUTATIONAL MODELLING WHICH
ALLOWS US TO SEE HOW DIFFERENT
PARAMETERS SUCH AS COIL POSITION
AND COIL TYPE AND STIMULATION
INTENSITY CAN INDUCE THE
ELECTRIC FIELD WITHIN THE BRAIN.
WITH MODELLING METHODS,
RESEARCHERS HAVE BEEN ABLE TO
DEVELOP HIGHLY ACTIVE RENDERING
BUT IT'S TIME CONSUMING RANGING
FROM SEVERAL HOURS TO MULTIPLE
DAYS DEPENDING ON THE NUMBER OF
MODELS THAT NEED TO BE GENERATE
AND IT'S RESULTED IN A
BOTTLENECK IN RESEARCH.
AND TO ADDRESS THESE ISSUES
WE'RE APPLYING METHODS FROM DEEP
LEARNING.
DEEP LEARNING MODELS USE
MATHEMATICAL ALGORITHMS TO
FILTER OUT KEY ASPECTS OF DETE
THROUGH A MULTI LAYERED NETWORK
AND DEEP LEARNING APPROACHES
SPECIFICALLY ONE APPROACH HAS
BEEN INCREASINGLY POPULAR WHEN
WORKING WITH MEDICAL IMAGES
BECAUSE OF THEIR ABILITY TO NOT
ONLY LEARN INFORMATION BUT
PRESERVE IT SPATIALLY.
WHILE IT'S A BEEN USED FOR IMAGE
SEGMENTATION WE'RE COVERING THE
NUANCES AND RELATIONSHIPS
BETWEEN OUR STIMULATION
PARAMETER AND SPANNING NEURO
ANATOMY TO OUTPUT.
TO ENSURE OUR MODEL IS ROBUST
WE'RE DEVELOPING A LARGE DATA
SET OF MRIs AND GENERATING
NUMERIC MODELS OF OVER 15,000
COIL SETTINGS.
OUR PRELIMINARY RESULTS SHOW
AFTER BEING TRAINED OUR DEEP
LEARNING MODEL IS ABLE TO MAKE
AN ESTIMATION OF THE ELECTRIC
FIELD IN 15 MILLISECONDS
COMPARED TO THE TRADITIONAL
PROCESS WHICH CAN TAKE TWO HOURS
WITH ACCURACY SHOWN IN THE
BOTTOM SLIDE.
AFTER DEVELOPING AND FINE TUNING
A MODEL TO ENSURE OPTIMAL
ROBUSTNESS AND WOULD ENABLE THE
CLINICAL SETTING.
IF YOU'RE INTERESTED IN A MORE
IN DEPTH SETTING STOP BY MY
POSTER NUMBER 803 WITH DEEP
LEARNING BASE AND ELECTRIC
FIELD.
THANK YOU.
>> HELLO.
I'M POST-DOC AT U.C. SAN
FRANCISCO.
HERE WE APPLY A COMPUTATIONAL
NEUROSCIENCE APPROACH TO LOOK AT
PATHOLOGY SUCH AS AN ALZHEIMER'S
DISEASE ALONG THE BRAIN'S
CONNECTOME.
THE AMYLOID IN ONE PORTION OF
THE GRAIN AFFECTS PROTEINS AND
HELPS PATHOLOGY
TRANSSYNAPTICALLY.
TAU CAN CASCADE THE MISFOLDING
ALONG THE PATHWAYS.
THIS TRANSMISSION UNDER LIES ALL
DEMEN
DEMENTIA.
OUR NETWORK DIFFUSION MODEL OR
NDM CAN MODEL SUCH PROGRESSION
OF ALZHEIMER'S NEUROPATHOLOGY
ALONG THE CONNECTOME AND
OPTIMIZING THE PARAMETERS OF
AMPLIFICATION OF PATHOLOGY.
ON THE PATHOLOGY CAN BE MODELLED
USING THE BRAIN'S CONNECT HOME
AND THE SURROUNDING NEUROLOGICAL
MOLECULES CAN ALSO INFLUENCE THE
SPREAD CLEARANCE AND AGGREGATION
OF PATHOLOGICAL ENTITIES.
WE HAVE EXAMPLE IN SILICO AND
INCLUDE SUCH AFFECTS.
ACTIVATION OF MICROGLIA THE
BRAIN'S IMMUNE CELLS IS A
CLASSIC FEATURE OF ALZHEIMER'S
DISEASE.
TAU DYNAMICS ARE INFLUENCED BY
THE ACTION OF MICROGLIA FOUND IN
THE VICINITY OF AGGREGATES.
MOUSE MODELS OF RAPID TAU
PROPAGATION HAVE DEMONSTRATE D
MICROGLIA CONTRIBUTE AND NO
SIMULATION OF THE AFFECTS OF
MICROGLIA EXIST SO FAR.
THE NOVEL MODEL SEEMS TO
QUANTIFY THE EFFECT OF MICROGLIA
AS MEDIATORS OF ABROGATION GIVEN
BY THE TERM IN FIGURE 1 AND
MICROGLIA AS MEDIATORS OF SPREAD
GIVEN BY THE TERM M BETA IN
FIGURE 1.
WE SET UP THE NEXUS MODEL AS
SHOWN IN FIGURE 2 USING TAU
PATHOLOGY DATA FROM MICE HAVING
INJECTIONS IN THE BRAIN AND
MICROGLIA GENES AND EXAMINE THE
INFLUENCE OF HOMEOSTATIC AND
ACTIVATED MICROGLIA AND
ACTIVATOR MICROGLIA IMPROVE THE
PREDICTIVE POWER AND APPEARED TO
REDUCE TAU RATE BY INCREASING
THE INTERREGIONAL SPREAD FROM
THE HIPPOCAMPUS CAUSING HIGHER
TAU BURDEN IN THE HIPPOCAMPUS.
THIS IS IN FIGURE 3 HERE THE
MAGENTA INDICATE THE FLOW OF TAU
UNDER THE INFLUENCE OF TREM 2
AND THE BLUE ARROWS SHOW THE
TRANSMISSIB
TRANSMISSIBILITY.
THIS APPROACH DEMONSTRATE THE
ABILITY TO NOT ONLY MODEL AND
PREDICT THE PROGRESSION OF
DISEASE, BUT ALSO TO INSPECT AND
QUANTIFY THE INFLUENCE OF OTHER
BIOLOGICAL ENTITIES AND LOOK AT
GENERATION AND PATHOLOGY
PROGRESSION.
THANK YOU.
>> OUR WORK LOOKS AT STIMULUS
AND TO GUIDE BEHAVIOR AND
OVERCOME SENSORY INFORMATION
SUCH AS VISUAL STIMULUS NEEDS TO
BE TRANSFORMED ACROSS MANY AREAS
OF THE BRAIN.
TEASING A PART THE
TRANSFORMATIONS REQUIRES PRECISE
CALCULATIONS.
TO THIS END WE DEVELOPED A
SYSTEM TO ALLOW ACCESS TO NEURON
ACTIVITY IN THE BRAIN AND CAN
EXPRESS CALCIUM CENSOR --
SENSOR IN AND COMBINE IT WITH
STIMULATION METHODS WHICH ALLOWS
US TO PRECISELY SELECT CELLS OF
INTEREST FOR TARGETED
STIMULATION.
FOR EXAMPLE, BASED ON THE
STIMULUS AND ACTIVITY AND YOU
CAN SEE WHERE CELLS ARE SELECTED
AND SEE RESPONSES THERE.
OUR RECENT WORK HAS BEEN TO LOOK
AT THE PRIMARY VISUAL CORTEX OR
V1 OF MICE.
AND SPECIFICALLY WE'VE
INVESTIGATED HOW INDIVIDUAL
CELLS IN THE CORTICO NETWORK
INFORM THE INPUTS THEY RECEIVE
BY MEASURING THEIR RESPONSES TO
A FIXED OPT OWO GEN -- OPTO
GENIC THREAT WORK AND PROVIDING
INPUTS WHICH CAN LEAD TO A
VARYING LEVEL OF ACTIVITY OR
SUPPRESSION IN DIFFERENT CELLS.
AND WHEN WE COMBINE THE SAME
OPTOGENETIC INPUT TO SINGLE
CELLS DURING VISUAL STIMULATION
AND SPONTANEOUS ACTIVITY, WE
FIND CELLS DON'T SHOW A CHANGE
IN THE MAGNITUDE OF THEIR
RESPONSE TO THE OPTOGENETIC
INPUT WHETHER THEY'RE, VISUALLY
EXCITED OR DRIVEN OR DURING
SPONTANEOUS ACTIVITY.
HOWEVER, WE DO FIND CELLS
EXPRESSED DUE TO A VISUAL
STIMULUS DECREASE THE MAGNITUDE
OFFIS THIS RESPONSE TO THE INPUT
DURING INPUT AS OPPOSED TO
SPONTANEOUS CONDITIONS WE CAN
SEE ON THE LEFT SIDE OF THE
SPLATTER PLOT ON THE BOTTOM
LEFT.
THIS INPUT ATTENUATION INDICATE
THE CELLS HAVE BEEN PUSHED TO A
REGIME OF TRANSFER FUNCTION.
WE CAN DEMONSTRATE FOR THE FIRST
TIME THE ACTUAL CELL TRANSFER
FUNCTION AND ESTIMATE THE
SPONTANEOUS BASELINE CONDITIONS.
WHAT WE FOUND ON AVERAGE CELLS
HAVE A SUPER LINEAR TO LINEAR
TRANSFER FUNCTION AND MOREOVER,
WE FIND CELLS SUGGEST ABOVE THE
BASELINE MEANING AS CELLS
EXCITED INCREASE AND OTHER CELLS
ATTENUATE RESPONSE AND THIS
SUGGEST THE CORTEX MAY ACT AS A
FILTER TO EXPRESS ANY INPUT
THAT'S UNRELATED TO THE VISUAL
STIMULUS AT HAND.
WE CAN IMAGINE THE FUNCTION MAY
BE BENEFICIAL FOR BEHAVIORS THAT
RELY ON PERCEPTION DETECTION OR
DISCRIMINATION.
WITH THE TOOLS WE'RE ABLE TO
UNCOVER THE COMPLEX
TRANSFORMATIONS THE NETWORK IS
PERFORMING AND HOPE TO PROBE THE
NETWORK AND UNCOVER HOW THEY
IMPACT BEHAVIORS USING THE
COMBINED METHODS.
I'M LOOKING FORWARD TO ANSWERING
YOUR QUESTIONS AND YOU CAN FIND
MORE DETAILS ON MY POSTER.
THANK YOU.
>> I'M A NEUROSCIENCE RESEARCH
FELLOW.
I WANT TO THANK THE NIH FOR THE
OPPORTUNITY TO SHARE OUR WITH
YOU.
I'LL DISCUSS MY RESEARCH IN
UNDERSTANDING THE DENDRITIC
ACTIVITY OF THE HIPPOCAMPUS
USING NEURON TRACING.
THERE ARE CONTRIBUTORS TO
SPECIAL EPISODIC MEMORY BY
FUNCTIONING AS CELLS.
PLACE CELLS ARE NEURONS THAT
FIRE AT DISTINCT LOCATION CALLED
PLACE FIELDS.
ACTIVITY ARE CORRELATED WITH
SPATIAL EPISODIC MEMBRANE.
THEY REMAP WHEN THEY'RE CORTEX
CHANGING BY SHOWING THE FIRING
PATTERN OR LOCATION OF THE PLACE
FIELDS.
DENDRITICS ARE DATA SENSORY AND
SPATIAL INPUTS.
DENDRITE ACTIVITY IS CRITICAL
FOR PLASTICITY AND MAY BE
RELEVANT FOR MAPPING.
FEW STUDIES ARE DIRECTLY
OBSERVED DENDRITE ACTIVITY.
OUR BRAIN INITIATIVE PROJECT IS
TO VALIDATE THE RELATIONSHIP
BETWEEN DENDRITES AND SOMA WITH
ENVIRONMENTS AND TASKS.
TO UNDERSTAND THE ACTIVITY, TWO
IMAGES WERE PERFORMED FOR THE
NEURONS OF MICE.
THE REGIONS OF INTEREST MUST BE
IDENTIFIED.
OUR GROUP IS DEVELOPING AN
AUTOMATED PROGRAM TO FIND THE
ROIs.
TO CONTRIBUTE TO THIS I CREATED
ROIs OF DATA SETS USING IMAGING.
IDENTIFIED DENDRITES USING A
SPECIFIC CONVENTION TO LINK SOMA
WITH THEIR DENDRITES.
IN THE IMAGE IN THE TOP PART
THERE'S A PICTURE WHAT THE
NEURON LOOKED LIKE THROUGH
IMAGING AND ANOTHER PICTURE OF
THE NEURON TRACING I DID.
IN WHICH I TRACED THE DENDRITES
AND SOMAS AND FOLLOWED THE
PREVENTION TO THE RIGHT.
THESE DRAWN ROIs WERE COMPARED
WITH ROIs WITH OUR AUTOMATED
PROGRAM AND THEN A PUBLISHED
PROGRAM CALLED SUITE 2P AND THE
DE -- THE PROGRAM IS SHOWN ON
THE BOTTOM RIGHT.
THE LABEL TOOK BETWEEN TWO 2 TO
50 HOURS DEPENDING ON THE
DENSITY OF NEURONS.
THE PROGRAM TOOK A FEW MINUTES
ON THE SAME DATA.
ROIs FROM SUITE 2P SENDED TO BE
MORE LIBERAL IDENTIFYING ANY
POTENTIAL GROUP OF PIXELS THAT
COULD BE A NEURON.
IN CONTRAST, OUR DENDRITE
DETECTION PROGRAM WAS MORE
CONSERVATIVE FOCUSSING ON NEURO
ACTIVITY AND LEAVING BACKGROUND
NOISE.
OUR PROGRAM ALSO HAS ZERO
PARAMETERS FOR SUITE 2P ARRIVED
AT ACCURATE DENDRITIC ROIs.
I'M SO EXCITED OUR DENDRITE
DETECTION PROGRAM WAS ABLE TO
RECOGNIZE ACTIVITY ACROSS SPACE
AND PRODUCE MEANINGFUL RESULTS.
IN THE FUTURE WE HOPE TO USE THE
NEW DETECTION PROGRAM TO FURTHER
EXPAND OUR KNOWLEDGE AND
RELATIONSHIP BETWEEN DENDRITES
AND SOMA OF THE SAME NEURONS.
AND ALSO UNDERSTAND DENDRITE'S
ROLE IN SPATIAL WORK IN MEMORY
AND EP SO THEIC MEMORY.
THANK YOU.
>> HI.
I'M EDNA NORMAN AND AN Ph.D.
CANDIDATE AT PRINCETON
UNIVERSITY.
RIGHT NOW YOU MIGHT BE ABLE TO
HEAR ME SPEAKING TO YOU AND YOU
MAY BE ABLE TO SEE MY FACIAL
EXPRESSIONS EVEN IF OVER ZOOM.
AND THE AUDITORY SIGNALS
CARRYING MY WORDS GET PROPAGATED
FROM YOUR EARS ALL THE WAY TO
YOUR CENTRAL BRAIN BY A SERIES
OF NEURONS IN THE AUDITORY
PATHWAY AND THE VISUAL SIGNALS
CARRYING SIGNALS ABOUT ANY
EXPRESSIONS AND BODY LANGUAGE
ARE PROPAGATED FROM YOUR EYES TO
YOUR CENTRAL BRAIN.
AND I WOULD TAKE THE
AUDIO/VISUAL FEEDBACK FROM YOU
AND THINK THEY'RE INTERESTED IN
WHAT I'M SAYING AND I'LL
CONTINUE TO RESPOND IN TIME TO
ARE TALK ABOUT THE PROJECT AND
BECOMES A DYNAMIC CONVERSATION.
IT'S NOT KNOWN HOW SIGNALS FROM
SENSORY MODALITIES SUCH AS
AUDITION AND VISION ARE
INTEGRATED AT THE CELL AND
SECTOR LEVELS AND HOW THEY DRIVE
RESPONSIVE BEHAVIORS IN REAL
TIME AND ECOLOGICALLY RELEVANT
AND INNATE INTERACTIONS SUCH AS
OUR CONVERSATION.
WE'RE WORKING TO BUILD A MODEL
HOW NEURONS ACQUIRE THEY'RE
DETECTION PROPERTIES DIRECTLY
FROM THEIR INPUTS AT THE CELL
AND CIRCUIT LEVELS AND INTEGRATE
SENSORS OVER TIME SUCH AS
THROUGHOUT THE CONVERSATION AND
HOW TO TRANSFORM THE SIGNALS
INTO DYNAMIC MOTOR RESPONSES.
BY MODELS WITH DROSOPHILA WE
MAPPED THE CIRCUIT IN WHICH
AUDITORY AND VISUAL PATHWAYS
CONVERGE WHICH HAPPENS WHEN THEY
SYNAPSE ON TO NEURONS THEMSELVES
DRIVE AND MODULATE BEHAVIOR.
TO DO THIS WE USE BOTH
CONNECTIVITY AND MORPHOLOGY TO
DISENTANGLE PREVIOUSLY
INDISTINGUISHABLE CELL TYPES.
TO QUANTIFY THE BEHAVIOR DRIVEN
BY THE CIRCUIT WE HAVE A MACHINE
LEARNING MODEL TO TRACK THE
INDIVIDUAL BODY PARTS OF EACH
FLY THROUGHOUT THEIR
AUDIO/VISUAL COURTSHIP
CONVERSATION.
WE TOOK AUDIO AND VISUAL
RECORDINGS OF FLY COURTSHIP
SESSIONS AND NEURONS
SPECIFICALLY THAT ARE IN THE
BEHAVIOR DRIVING CIRCUIT.
TO UNDERSTAND HOW AUDIO/VISUAL
SIGNALS ARE DRIVING APPROPRIATE
RESPONSIVE BEHAVIOR.
WE'RE ALSO RECORDING NEURAL
ACTIVITY AT THE CELLULAR NODE OF
INTEGRATION TO UNDERSTAND THE
COMPUTATIONS.
WE'RE WORK TOWARDS OUR GOAL OF
MAPPING MULTISENSORY INTEGRATION
ACROSS THE CELL AND CIRCUIT AND
ACROSS THE BEHAVIOR LEVELS.
IN ADDITION, THE MODEL PROVIDES
A FRAMEWORK FOR GENERALLY
PROBING HOW THE INTEGRATION OF
SIGNALS FROM DISTINCT CELL TYPES
DIRECTLY DRIVE ECOLOGICALLY
RELEVANT SOCIAL BEHAVIOR.
I'D LOVE TO CONNECT WITH YOU AND
AS A SCIENTIST TRAINEE I'M
INTERESTED IN CONNECTING WITH
PEOPLE APPLYING TO STEMS AND
CIRCUITS NEUROSCIENCE AND
COMPUTATIONAL MODELS TO CLINIC
AND TRANSLATIONAL PROBLEMS SO
PLEASE REACH OUT AND FINALLY
THANK YOU TO THE NIH BRAIN
INITIATIVE CONVERSATION
ORGANIZERS FOR THE OPPORTUNITY
TO GIVE THE TALK.
>> I'M A POST-DOC AT THE
UNIVERSITY OF CALIFORNIA SANTA
BARBARA.
MY RESEARCH INTEREST IS IN
DEVELOPING AND DISSEMINATING NEW
TECHNOLOGIES FOR IMAGING FOR THE
NEUROSCIENCE COMMUNITY.
CALCIUM IMAGING CAN RECORD THE
ACTIVITY OF BEHAVING ANIMALS
WITH HIGH TEMPORO RESOLUTION
MAKING IT A USEFUL IMAGING TOOL
FOR STUDYING COMPUTATION IN
NEURAL CIRCUITRY.
TO APPLY THE TECHNOLOGY A
PORTION IS SURGICALLY DE MOVED
TO IMPLANT A WINDOW AND PROVIDE
ACCESS FOR IMAGING.
THE DESIGN OF THE WINDOW DEPENDS
ON THE OBJECTIVES.
COMMERCIALLY AVAILABLE IMAGING
OFFER ALMOST ALWAYS LESS THAN 10
MILLIMETER AND THERE'S BEEN
CHALLENGES IN LARGE MAMMALS SUCH
AS MONKEYS AN FERRETS.
BECAUSE CREATING THE APERTURE
ENTAILS EXPRESSIVE REMOVAL OF
TISSUE AND SKULL.
AND THIS LEADS TO INCREASED
RESPONSES AND COMPROMISED
IMAGING AND THE IMAGING
EXPERIMENTS.
IN ADDITION, POPULAR COMMERCIAL
OBJECTIVES POSE AN ADDITIONAL
CHALLENGE WHEN IMAGING
NON-HORIZONTAL SURFACES SUCH AS
AREAS SIDES OF BRAINS AS IT'S
DIFFICULT TO MAINTAIN THE WATER
INTERFACE AT AN ANGLE.
TO ADDRESS THESE ISSUES WE
DEVELOPED A 20 MILLIMETER
WORKING DISTANCE OBJECTIVE SO
THE FRONT END OF THE OBJECTIVE
IS AT A LARGE DISTANCE FROM THE
BRAIN.
THIS PREVENTS EXCESSIVE TISSUE
REMOVAL AND THUS REDUCES IMPACTS
ON BRAIN HEALTH.
IN ADDITION WE DESIGNED AN
OBJECTIVE MEANING NO MATTER OR
LIQUID IS REQUIRED SO WE'RE
TAKING THE OBJECT AT AN ANGLE
AND APPROACHING THE SIDE OF
BRAIN REQUIRES NO WATER
INTERFACE.
THIS OBJECTIVE IS DESIGNED FOR
IMAGING INDICATORS LIKE G-CAMP.
IT'S OVER A 2 MILLIMETER FIELD
OF VIEW TO RECORD A LARGE
POPULATION OF NEURAL ACTIVITY.
THE OBJECTIVE PROVIDES CELLULAR
RESOLUTION AND HAS HIGH
EXCITATION AND COLLECTIONS.
TO ENSURE THE OBJECTIVE IS
COMPATIBLE WITH COMMERCIAL 2
PHOTON MICROSCOPE WE USED THE
APERTURE AND DISTINCT ANGLES
COMMONLY AVAILABLE IN SUCH
SYSTEMS.
WE HOPE THAT THIS NEW CUSTOM
DESIGN OBJECTIVE ADDRESS A
MARKET GAP LEFT BY OBJECTIVES
AND ULTIMATELY ENABLE NEW
NEUROSCIENCE EXPERIMENTS.
IMPORTANTLY, WE PROVIDE A NOVEL
EXAMPLE THAT IT IS POSSIBLE TO
DESIGN YOUR OWN OPTICS INCLUDING
MICROSCOPE OBJECTIVES TO BEST
FIT YOUR UNIQUE IMAGING
CONDITIONS.
IN ORDER TO FACILITATE THE
DISSEMINATION AND ENCOURAGE
FURTHER CUSTOMIZATION, WE
RELEASED OUR DESIGN DESCRIPTION
WITH OUR PATTERNS OR LICENSES SO
IT IS AN OPEN SOURCE TO
EVERYONE.
PLEASE COME TO MY POSTER TO SEE
MORE DETAILS ON THE DESIGN AND
PROVIDE INSIGHTS ON WHAT TYPES
OF OBJECTIVES OR WHAT ARE
DESIRED BUT YET MISSING FOR
NEUROIMAGING.
THREW FOR YOUR LIST -- THANK YOU
FOR YOUR LISTENING.
>> I'M AN M.D. Ph.D. STUDENT IN
SAN DIEGO.
I'LL DISCUSS A CIRCUIT METHOD
START WHICH STANDS FOR SINGLE
TRANSCRIPTOME RABIES TRACING.
THE CEREBRAL CORTEX HAS DISTINCT
MOLECULAR AND MORPHOLOGICAL AND
PHYSIOLOGICAL PROPERTIES.
T
THE NEURONAL DIVERSITY MAY BE
GREATER THAN IMAGINED BUT THE
CELLS DO NOT FUNCTION IN
ISOLATION.
RATHER, THEY TALK TO ONE ANOTHER
THROUGH HIGHLY COMPLEX CIRCUIT
GIVE RISE TO CORTICO PROCESSING.
THUS TO UNDERSTAND CORTICO ING
IT'S NECESSARY TO GAIN INSIGHT
NOT ONLY ABOUT THE VAST AMOUNT
OF DIFFERENT CELL TYPES FROM THE
CORTEX BUT ALSO THE PRECISE WAYS
THEY ARE CONNECTED TO ONE
ANOTHER.
WE THEREFORE SOUGHT TO DEVELOP A
WAY TO REVEAL CONNECTIVITY OF
NEURONS AS LEVEL CELL TYPES
DEFINE THE GENE EXPRESSION AND
COMBINE TRACING AND SINGLE
NUCLEI RNA SEQUENCING TO
IDENTIFY THE TRANSCRIPTOMIC CELL
TYPES THAT PROVIDE MONOSYNAPTIC
INPUT TO DEFINE POPULATION OF
NEURONS.
BECAUSE RABIES INFECTION CAN
INFLUENCE GENE IN HOST CELLS
THROUGH THIS VALIDATION WE
ESTABLISHED WHETHER RABIES
INFECTED NEURONS COULD BE
CLASSIFIED ACCORDING TO
RECOGNIZED TRANSCRIPTOMIC
CORTICAL CELL TYPES AND WE
LOOKED AT RNA PROFILES RABIES
INFECTED CORTICAL NEURONS CAN BE
CHARACTERIZED DESPITE GLOBAL AND
CELL TYPE SPECIFIC RABIES
INDUCED TRANSCRIPTIONAL CHANGES
WE'RE CURRENTLY USING START TO
DISTINCT CORTICAL LAYERS IN MICE
PRIMARY VISUAL CORTEX.
THUS FAR WE HAVE TRANSCRIP
TRANSCRIPTOTRANSCRIP
TRANSCRIPTOMICLY LABELLED
NEURONS.
AT THE SUBCLASS LEVEL CONSISTENT
WITH CANONICAL MODELS LAYER 4
NEURONS REPRESENTED THE LARGEST
SOURCE OF INPUT AND OUR FINDINGS
ARE LARGELY IN AGREEMENT WITH
PRIOR WORK.
SUGGESTING START IS CAPABLE OF
CHARACTERIZING INPUT CELLS
COMPARED TO CURRENTLY AVAILABLE
METHODS.
MORE IMPORTANTLY, THE IMPROVED
CELL TYPE GRANULARITY WAS
ACHIEVED WITH TRANSCRIPTOMICS
INPUTS WE WERE ABLE TO LOOK AT
INTERNEURONS THAT PROVIDE INPUT
TO LAYER TWO THREE OR EXCITATORY
NEURONS SOMETHING THAT THE
PREVIOUSLY POSSIBLE WITH
CIRCUITRY TOOLS.
OVER ALL, THIS CAN HELP
DISENTANGLE THE RESOLUTION AND
EXPAND THE REPERTOIRE OF POOL
AVAILABLE TO NEUROSCIENTISTS
STUDYING DIFFERENT CORTICAL
AREAS IN HEALTH AND DISEASE.
THANK YOU FOR ATTENDING.
>> I'M AT CENTRAL MICHIGAN
UNIVERSITY.
THE TITLE OF MY TALK IS DELIVERY
OF PLASMIDS USING SURFACE
MODIFIED MOLECULES IN AN IN
VITRO STUDY.
WE HAVE MOLECULES THAT HAS THE
ABILITY TO CARRY LARGE PLASMIDS
AND DRUGS TO THE CELLS IN VIVO.
THESE DO NOT HAVE ANY CARGO
CARRYING LIMITATIONS TO THEM.
THEY HAVE THE CORE, WHICH IS THE
CENTRAL PART AND THE DENDRIMER
AND THE DIFFERENT SIZES.
THEY ALSO HAVE SURFACE GROUPS
WHICH ARE PRESENT AT THE SURFACE
OF THE DENDRIMER.
THE ONES COMMERCIALLY AVAILABLE
BUT HIGHLY TOXIC TO THE CELLS IN
VIVO AND IN VITRO.
WE HAVE SURFACED MODIFIED OUR
DENDRIMERS SUCH AS A G4910 AND
THEY HAVE 90% HYDROXL GROUPS AND
G4-70/30 DENDRIMERS HAVE 30%.
AND REDUCING THEM FROM 100% TO
10% OR 30% WE'RE REDUCING THE
TOXICITY OF THE DENDRIMERS.
IN THE STUDY WE USED A G1 AND G2
DENDRIMERS AND THEY ARE COMPLEX
WITH PLASMID OF 8.4KB.
COMPLEXING THESE THEY WERE
INCUBATED AT DIFFERENT
CONCENTRATIONS TO THE RAT
PRIMARY CORTICAL NEURONS AND THE
COMPLEX UPTAKE GENE EXPRESSION
AND TOXICITY PROFILE AND
ACTIVITIES.
WE FOUND THE DREN DENDRIMERS
WERE UPTAKEN BY THE NEURONS AND
WERE ABLE TO SEE THE GENE
EXPRESSION SHOWING THE
DENDRIMERS SUCCESSFULLY
DELIVERED THE PLASMID AND THE
GENE WAS EXPRESSED.
UPON ANALYZING THE TOXICITY WE
FOUND THE DENDRIMERS WERE NOT
TOXIC TO THE NEURONS AND THEY
WERE ABLE TO MAINTAIN THEIR
NEURONAL ACTIVITY.
WE WANTED TO IMPROVE THE
EFFICACY AND THE UPTAKE BY THE
NEURONS.
FOR THIS PURPOSE WE USED AN
ACTIVATED DENDRIMER WHERE THEY
WERE HEAT ACTIVATED FOR 40
DEGREES FOR 24 HOURS OR 48
HOURS.
AS YOU CAN SEE FROM THE FIGURE
HERE, THE DENDRIMER AND THE
COMPLEXES WERE UPTAKEN BY THE
NEURONS WHEN THEY WERE ACTIVATED
COMPARED TO THE DENDRIMERS IN
THE COMPLEXES NOT ACTIVATED.
CURRENTLY, ONGOING DENDRIMER
MODIFICATIONS INCREASE CARGO
SIZE AND DISTRIBUTION IN VIVO TO
LEAD TO A NON-INVASIVE MOLECULAR
TOOL FOR THE BRAIN.
THANK YOU.
>> I'M A POST-DOCTORAL FELLOW IN
THE LABORATORY.
MY WORK FOCUSES ON UNDERSTANDING
THE NEURAL CIRCUIT MECHANISMS
UNDERLYING COGNITION AND THOSE
WHICH INVOLVED FLEXIBLY
RESPONDING TO STIMULI DEPENDING
ON CONTEXT.
CLASSICAL EXAMPLE PARADIGM USES
RANDOM DOTS FOR MOTION,
DIRECTION AND COLOR IN ANIMALS
WIN A CONTEXTUAL CUE AND WITH
THE ANIMAL HAS TO RESPOND
DIFFERENTLY TO THE SAME STIMULI
DEPENDING ON CONTEXT.
SO THIS BEHAVIOR IS A HALLMARK
OF COGNITIVE FLEXIBILITY.
ONE CHALLENGE IN UNDERSTANDING
HOW THE BRAIN ACCOMPLISHES THIS
IS THE COMPLEXITY OF SINGLE CELL
RESPONSES OBSERVED IN FRONTAL
BRAIN REGIONS.
IN PARTICULAR, PREFRONTAL CELLS
OFTEN RESPOND TO TASK-RELEVANT
VARIABLES AND IS AN OBSTACLE IN
THE RELATIONSHIP BETWEEN
ACTIVITY AND BEHAVIOR.
WE DEVELOPED A COMPUTATIONAL
FRAMEWORK WHICH LIES AT THE
INTERSECTION OF DIMENSIONALITY
REDUCTION AND ACTIVITY WHICH
UNCOVERS HOW SPATIALLY
DISTRIBUTED PATTERNS INTERACT TO
AFFECT BEHAVIOR.
OUR APPROACH SIMULTANEOUSLY LY
INFERS A CIRCUIT WHICH GENERATES
THE DYNAMICS IN THE SUBSPACE.
THE RESULTING CONNECTIVITY LOOKS
AT DYNAMICS BEING GENERATED IN
THE BRAIN.
APPLYING THIS FRAMEWORK TO
RECORDINGS FROM THE PREFRONTAL
CORTEX OF RHESUS MONKEYS
REVEALED A MECHANISM WHERE
NEURONS REPRESENTING CONTEXT
FLEXIBLY INHIBIT ONE OF TWO
RESPONSE ASSOCIATIONS.
SO THIS COULD BE OBSERVED IN
NEURAL ACTIVITY BY PROJECTING
HIGH DIMENSIONAL RESPONSES ON TO
THE SUBSPACE IDENTIFIED BY THE
LATENT CIRCUIT MODEL AND
STIMULATIONS SUPPRESSED WHEN
IRRELEVANT AND IT'S AN EXCITING
APPROACH TO CONNECTIVITY
INFERENCE TESTING HYPOTHESES
UNDERLYING COGNITION AND
INTERPRETABLE SECTOR MECHANISMS
FROM NEURAL RECORDING DATA THUS
PROVIDING A FRAMEWORK FOR
UNDERSTANDING HOW CONNECTIVITY
PRODUCES BEHAVIOR IN HIGHER
CORTICAL AREAS.
THANK YOU FOR YOUR ATTENTION AND
IF YOU'RE INTERESTED COME LOOK
AND LOOK AT OUR POSTER.
>> WOW.
AMAZING PRESENTATIONS.
SURELY EVERYONE WATCHING THESE
CAN SEE WHY THESE SCHOLARS AND
RESEARCHERS WERE SELECTED.
JUST FABULOUS.
AND SO WELL DONE WITH THE TIME
ALLOTTED.
REALLY IMPRESSIVE.
LET'S JUMP RIGHT INTO SOME
QUESTIONS WE HAVE IN THE Q&A AND
IF YOU HAVE MORE JUST CONTINUE
TO ADD THEM WE'LL JUST GO IN
ORDER OF THE VOTES.
WE'RE GOING TO START OFF WITH
SANDRA.
DOES THE STIGMA WITH P.I.s HAVE
ANY GENDER DIFFERENCES?
>> THE STIGMA ASSOCIATED WITH
DEPRESSION AND STIGMA THAT
TREATMENTS CARRY AND A MEAN
ANTIDEPRESSANTS AND
PSYCHOLOGICAL THERAPIES.
IN TERMS OF GENDER, I THINK WE
SEE STIGMA AFFECTS MEN MORE THAN
WOMEN.
MEN IN THE MILITARY IS WHAT IT
EXEMPLIFIED FOR US.
WITHIN THE U.S. CONTEXT, WE'RE
SEEING STIGMA RELATED TO THE
CONDITION AND RELATED TO THE
TREATMENT INTENSIFIES ACCESS TO
RACIAL MINORITIES.
AND THIS MIGHT BE FOR ALL KINDS
OF REASONS.
ONE IS DUE TO INEQUALITIES IN
THE INFRASTRUCTURE.
AND IT MIGHT ALSO BE BECAUSE OF
DIAGNOSIS OF TREATMENT MAY HAVE
CONTRARY VALUES.
AND IT MAY BE A FORCE OF SHAME
AND DEPRESSION IS DIAGNOSED AND
THEN TREATED.
IN TERMS OF THE THERAPY THE
TECHNOLOGIES, WE DIDN'T REALLY
FIND THIS IN OUR DATA WHICH IS
INTERESTING THOUGH IT SUGGESTED
IT IN THE LITERATURE AND THERE'S
METHODOLOGICAL REASONS FOR THAT
AND ONE IS STIGMA IS NOT A
CONCEPT THAT MIGHT BE IN THE
GENERAL PUBLIC.
IT'S NOT READILY RECOGNIZABLE.
IT'S A TERM ACADEMICS TEND TO
USE AND INFLUENCE THE
PERCEPTION.
I THINK THE PSYCHIATRISTS
PARTICIPATED IN OUR STUDY
CONFIRM STIGMA IS IN THE TOP
AREA WITH THIS TECHNOLOGY.
>> THANK YOU SO ECH.
I'M S YOU CAN TELL US MORE
BUT WE'LL TRY TO SEND PEOPLE TO
YOUR POSTER.
THANK YOU FOR YOUR ANSWER.
>> THANK YOU.
>> PLEASE DO VISIT THE POSTERS
FOR FOLLOW-UP QUESTIONS.
THE NEXT QUESTION IS IS DO THEY
ACROSS THE BLOOD BRAIN BARRIER
AND WHAT MODIFICATIONS MAY
AFFECT DELIVERY TO CELL TYPES AS
AN ADDITIONAL APPROACH ABOVE AND
BEYOND USING PROMOTERS AND
ENHANCERS AND THE LIKE.
>> THAT'S A GREAT QUESTION.
THANK YOU.
TO ANSWER YOUR FIRST QUESTION,
YES, THEY ARE ABLE TO ACROSS THE
BLOOD BRAIN BARRIER AND WE HAVE
PUBLISHED A COUPLE PAPERS WHICH
SHOWED WHEN WE INJECT THE
DENDRIMERS IN THE WING OF THE
RODENTS, WE WERE ABLE TO SEE THE
DENDRIMERS IN THE BRAIN.
AND TO MAKE IT CELL SPECIFIC, WE
CAN HAVE TWO APPROACHES.
FIRST WOULD BE WE CAN HAVE A
PROMOTER.
THE PLASMIDS THOUGH IT'S
EXPRESSED ONLY IN CERTAIN CELL
TYPES BASED ON THE PROMOTER, WE
CAN ALSO HAVE ANTIBODIES THAT
CAN BE TAGGED TO THE DENDRIMERS
AND THEY'LL GO BIND TO THE
SURFACE OF CERTAIN CELL TYPES
AND THEN THE DENDRIMERS CAN
DELIVER THE CARGO.
THEY CAN DELIVER THE PLASMID AND
THE DRUGS TO HAVE THE DNA AND
THE DRUG DELIVERED TO SPECIFIC
CELL TYPES AT THE SAME TIME.
>> GREAT.
IT'S NICE TO SEE SOME VIABLE
ALTERNATIVES TO WERE GREAT AND
WE'RE ALWAYS LOOKING FOR
DIFFERENT APPROACHES THAT CAN
CIRCUMVENT SOME LIMITATIONS.
WE'LL HAVE TO LOOK FORWARD TO
MORE PROGRESS.
>> GREAT.
>> NICOLE.
THE VENTRAL STRIATUM IS A
FAVORITE LOCUS FOR OCD AND
OTHERS.
HOW IS THIS CHOSEN FOR YOUR
PROJECT AND HOW GENERALIZABLE DO
YOU THINK THE LOCUS WILL BE FOR
OTHER DISORDERS?
>> THANK YOU FOR THE QUESTION.
THE VENTRAL STRIATUM TARGET WAS
INITIALLY CHOSEN BASED ON THE
TARGETS ABLATED DURING
PROCEDURES FOR OCD.
INITIALLY, DBS TARGETED THE
ENTIRE LIMB OF THE CAPSULE BUT
OVER TIME THE TARGET WAS REFINED
TO THE NUCLEUS ACO KCCUMBENS AN
OPTIMIZED THIS DURING BEHAVIORAL
TESTING DURING WHICH WE EVALUATE
ACUTE AFFECTS ON MOOD ANXIETY
AND ENERGY AND TYPICALLY SEE
SMILING, LAUGHTER AND POSITIVE
MOOD EFFECTS WHEN SIMULATION IS
TURNED ON IN O.R. AND USE THESE
FOR THE CONTACT OUT OF THE FOUR
OPTIONS THAT WE'RE USING.
AFTER DBS WE SEE DEPRESSION IN
MOOD STATES AND THIS MAY BE A
SECONDARY EFFECT.
SO THE INITIAL PERIOD IS WHEN WE
HAVE TO BE AWARE OF ONSET OF
HYPOMEAN -- HYPOMEAN IA AND THE
INTERNAL LIMB OF THE CAPSULE
CONNECT THE VENTRAL STRIATUM TO
MANY REGIONS INCLUDING THE
DORSAL ANTERIOR AND PREFRONTAL
CORTEX.
BECAUSE OF THE HIGH DEGREE OF
CONNECTIVITY AND THE INITIAL
IMPROVEMENTS IN MOOD AND ENERGY
WE TYPICALLY SEE, I THINK THIS
TARGET HAS THE POTENTIAL FOR
TREATING DISORDERS INVOLVING
MOOD, DYSREGULATION AND REWARD
AND ADDICTION AND DISORDER
EATING AMONG OTHERS.
AND THEY'RE LOOKING TO TACKLE
THE QUESTION OF HOW THE TARGET
MAY BE APPLIED TO OTHER
DISORDERS.
BE SURE TO CHECK THAT OUT.
>> SO YOU'RE SEEING THE HUB
FEATURE THE HUB NATURE AS A
FEATURE BECAUSE ONE ISSUE IS
GOING TO BE WHAT ARE THE OTHER
FOLLOW-ON OR SIDE EFFECTS.
IT'S INTERESTING THAT THE OCD
EFFECTS MANIFEST LATER SO THE
QUESTIONNAIRE IS HOW MUCH
PLASTICITY IS BEING INDUCED
BECAUSE OF THE STIMULATION.
>> THAT'S A GOOD QUESTION AND
THE FEATURE VERSUS BUG IS A GOOD
QUESTION TOO.
AS WE'RE ABLE TO DELIVER
STIMULATION MORE SPECIFICALLY
LIKE USING NEEDS TO SPECIFIC
PARTS OF THE VCVS TARGET WE MAY
SEE QUICKER RESULTS IN TERMS OF
OCD SYMPTOM IMPROVEMENT.
FUTURE WORK WILL HAVE TO LOOK
INTO THAT.
>> COOL.
THE NEXT QUESTION IS TO JAY AND
RELATED TO THE PREVIOUS ONE
FIRST OF ALL, COOL STUFF.
CLOSED LOOP STIMULATION SEEMS
PROMISE.
HOW IMPORTANT DO YOU THINK IT
WILL BE TO TAILOR THE STIMULUS
ON A MOMENT BY MOMENT BASIS
VERSUS OVER A MORE LONG-TERM
CHRONIC STIMULATION ONCE YOU
FOUND THE EFFECTED LOCUS?
>> THANK YOU FOR THE QUESTION.
WHEN WE THINK OF THE SYMPTOMS
THAT COULD BE EPISODIC IN TERMS
REEXPERIENCING EPISODES OF
HYPERVIGILANCE VERSUS MORE
CHRONIC SYSTEMS LIKE NEGATIVE
MOOD AND I THINK BECAUSE THE
DISEASE CAN BE BOTH BOTH CHRONIC
AND CONTINUOUS OVER TIME BUT
ALSO QUITE EPISODIC, I THINK
BOTH WILL BE QUITE IMPORTANT.
WE ALSO HAVE A BIT OF EVIDENCE
THAT MOMENT TO MOMENT
STIMULATION MAY BE A GOOD
CANDIDATE FOR TREATING
TREATMENT-RESISTANT PTSD BECAUSE
THERE WAS A PRIOR TRIAL FOR
IMPLANTATION OF DBS ELECTRODES
STIMULATION IN TREATMENT
RESISTANT PTSD AND THE PATIENTS
RECEIVING THE STIMULATION ARE
DOING A BIT BETTER THAN THOSE
RECEIVING THE DBS.
I THINK SOME CONTRIBUTE BEING
FACTOR TO THAT IS THAT WITH
CHRONIC DBS THE ONLY READOUT YOU
HAVE IS THE PATIENT'S SUBJECTIVE
EVALUATION OF HOW THEY'RE DOING
WHILE WITH RESPONSIVE NEURAL
STIMULATION WE'RE ALSO TO
STIMULATE AND SENSE AND HAVE AN
ELECTROPHYSIOLOGICAL BIOMARKER
THAT GIVES SOMETHING TO SINK
YOU'RE TEETH INTO MORE IN TERMS
OF HOW THE PATIENT IS DOING.
IT'S UNSATISFYING SAYING BOTH
WILL BE QUITE IMPORTANT BUT
THAT'S WHAT I THINK SO FAR
SPECIFICALLY AS IT RELATES TO
THE SYSTEMS RELATED TO PTSD.
>> THE EPISODIC READOUT COULD BE
KEY?
>> EXACTLY.
>> AND THE BIOLOGICAL MARKERS.
>> NICOLE, DID HAVE YOU A
COMMENT?
>> WE'RE THINKING ABOUT THE SAME
THINGS WITH REGARDS TO OCD IS IT
EPISODIC LIKE IS SOMEONE EXPOSED
TO A TRIGGER OR THE SLOWER
EVOLVING STATE?
I THINK THERE'S TWO CAMPS OF
THOUGHT ON THAT AND IT'S
PROBABLY BOTH.
OTHER THING FOR CLOSED LOOP OCD
THE FIRST COUPLE WEEKS TO MONTHS
AFTER DBS IS TURNED ON PATIENTS
GET HYPOMANIC.
WHILE DR. GOODMAN THE P.I. OF
THE STUDY TYPICALLY TWEAKS
AMPLITUDE A LOT IN THE FIRST
WEEKS TO AVOID THE ONSET OF
HYPOMANIA.
ONE IMPORTANT THING TO CONSIDER
FOR CLOSED LOOP IS CAN WE REDUCE
THE NUMBER OF VISITS AND THE
TWEAKS BY USING ADAPTIVE DBS IF
WE COULD HAVE A BIOMARKER OF
WHEN SOMEONE IS BECOMING
HYPERMANIC OR MANIC AND TURN
STIMULATION DOWN WOULD MAKE DBS
MORE ACCESSIBLE BY OTHER
PSYCHIATRISTS AND NON-EXPERT
CENTERS.
>> THANK YOU, JAY AND NICOLE, I
SEE A COLLABORATION COMING.
NANCY, YOU PROPOSED YOUR SET UP
COULD BE A TOOL THAT COULD GO
BEYOND NEURONS.
YOU SHOWED NEURONS BUT WHAT
ADAPTIONS DO YOU THINK WOULD BE
NEEDED TO DO THIS IN MUSCLE?
>> THIS IS A WONDERFUL QUESTION.
OPTICAL SYNAPSE CAN BE APPLIED
AND WE CAN TEST THIS AND THE
PARTNERSHIP IS BETWEEN A NEURON
AND MUSCLE AND MOTOR NEURON AND
SKELETAL MUSCLE.
IF YOU WANT TO TARGET THE
PARTNERSHIP IN A SPECIFIC WAY
AND SO HERE THE ELEMENTS CAN BE
MADE TO EXPRESS AND WE HAVE A
GENE EXPRESSION AND CAN BE
EXPRESSED BY THE SKELETAL MUSCLE
AND EXPRESS WHAT CAN BE TARGETED
AND THE POTENTIAL APPLICATION
AND WE HAVE SYNAPTIC
COMMUNICATION AND THE ANTIBODIES
AGAINST THE NEUROTRANSMITTER
RECEPTOR ON THE SKELETAL MUSCLE.
AND THIS WAY WE CAN ADOPT THE
OPTICAL SYNAPSE AND TARGET OTHER
PARTNERSHIPS IN THE MUSCLE.
THANK YOU.
YOU CAN DRIVE SOCIAL BEHAVIOR.
>> AS THE ONE OF MANY MORE
EXAMPLES TO COME BY HOW MUCH THE
STEPS WILL HELP SHAPE THE
HYPOTHESES AND GIVE RISE TO NEW
IDEAS FOR TESTING THEM.
>> THE FOCUS OF ALL --
ULTRASOUND IS AFFECTIVE AND HOW
DOES IT AFFECT THE STRUCTURE OF
CELLS BEING QUERIED.
>> IT'S KNOWN TO MODULATE NEURAL
ACTIVITY AND THERE'S A COUPLE
STUDIES THAT SHOW YOU CAN USE IT
TO ACTIVATE CELLS AND YOU CAN
LOOK AT BUCKLING THE STRUCTURE
OF THE NON LINEAR SIGNAL THAT
CONCERN THE BUFFERING OF THE
VESICLE.
SO I HOPE THAT ANSWERED THE
QUESTION.
>> GREAT, THANKS.
>> HELP US TO UNDERSTAND BETTER
THE DENDRITE'S ROLE IN A WORKING
MEMORY.
>> YES.
THANK YOU FOR THE QUESTION.
IF YOU HAVE AN AMOUNT OF TRIALS
IT'S HELPFUL TO RECORD MANY
DENDRITES AT ONCE TO UNDERSTAND
WHAT IS GOING ON.
OUR PROGRAM ALLOWS USERS TO
RECORD AND MAKE SENSE OF MANY
DENDRITES OR A LARGE DATA SET OF
NEURONS ALL AT ONCE WHICH WILL
BE HELPFUL FOR WORK.
I'LL EXPLAIN MORE WHAT OUR
PROGRAM CAN DO IN THE POSTER IF
YOU WANT TO CHECK THAT OUT.
>> FIRST, EVERYBODY WANTS TO
GIVE YOU KUDOS FOR MAKING THIS
AMAZING TOOL OPEN SOURCE.
EVERYONE IS REALLY EXCITED ABOUT
THAT.
THE FIRST QUESTION IS CAN THIS
LENS BE EASILY USED FOR MODIFIED
FOR USE FOR MICROSCOPY AND THE
SECOND IS DOES THIS NEED TO TAKE
PLANS TO FABRICATE AN OBJECT.
LET'S LET YOU TACKLE THOSE TWO
FIRST.
>> THANK YOU.
THESE ARE GREAT QUESTIONS.
SO FOR MODIFYING FOR MICROSCOPY,
AS I KNOW THERE'S MANY VARIANTS
OF MICROSCOPY AND SO THE DESIGN
SPECIFICATION PLAY VARY A LOT.
SO WE HAVE BEEN VERY INTERESTED
IN DEVELOPING MICROSCOPY IN THE
LAB.
WE'RE HAPPY TO SEE IF WE CAN
COME UP WITH A SOLUTION FOR YOU
SO PLEASE SEND ME AN E-MAIL FOR
FURTHER DISCUSSION AND THE OTHER
QUESTION IS ABOUT THE
MANUFACTURING THE LINKS.
SO I HAVE TO SAY THE FABRICATION
IS UNIQUE EXPERTISE AND REQUIRES
MANY HIGH PRECISION INSTRUMENTS
TO ASSEMBLE THE LINKS TOGETHER.
SO WE DO NOT HAVE THE EXPERTISE
NOR THE INSTRUMENTS IN OUR LAB
TO ASSEMBLE THE OBJECTIVE.
SO WE ACTUALLY CONTRACT THE WORK
TO EXTEND FOR VERIFICATION AND
ASSEMBLY.
BUT HAVING SAID THIS AGAIN, AS
THE DESIGNER OF THE OBJECTIVE,
WE HAVE ALL THE DESIGN
PARAMETERS AND MANUFACTURING
DETAILS.
IT IS CONVENIENT FOR THE FUTURE
USES TO MAKE THIS OBJECTIVE
WITHIN UP TO MODIFY IT TO BEST
FEED THE UNIQUE CONDITIONS.
>> AND THEN THE FINAL ONE WAS
ABOUT THE 28 MILLIMETER.
THE WORKING DISTANCE AIR
OBJECTIVE, CAN IT BE USED FOR
ANY STANDARD MICROSCOPY.
?
>> WE TRIED TO MAKE SURE IT CAN
BE COMPATIBLE WITH COMMERCIAL
INSTRUMENTS.
IT'S M32 AND STANDARD YOU SHOULD
BE ABLE TO DIRECTLY USE MANY
COMMERCIAL SYSTEMS HAVE THIS
SIZE OTHERWISE YOU CAN EASILY
USE AN ADAPTER TO CHANGE IT
BETWEEN DIFFERENT SIZES.
I BELIEVE IT SHOULD BE EASY FOR
YOU TO USE IT IN DIFFERENT
STANDARD MICROSCOPES.
>> THANK YOU FOR THAT.
I ENCOURAGE PEOPLE TO VISIT YOUR
POSTER.
OBVIOUSLY YOUR VERY OPEN TO
COLLABORATING AND SHARING THE
RESOURCE AND PEOPLE NEED TO
REACH OUT AND TAKE YOU UP ON
YOUR OFFER.
JOHN.
>> THIS IS A COOL TECHNIQUE.
HOW DOES IT COMPLEMENT PREVIOUS
STUDIES FROM YOUR LAB USING AAB
TRACING.
>> IN THE PAST MY LAB HAS
TRANSCRIPTOMICALLY HAD INPUT TO
A REGION THEY INFECTED SO THE
DIFFERENCE WITH THE MONOSYNAPTIC
TRACING IS YOU CAN TARGET
SELECTION TO A CELL POPULATION
OF INTEREST.
WITH RABIES YOU CAN SAY IN A
PARTICULAR REGION I ONLY WANT TO
LOOK AT INHIBITORY NEURONS WHERE
YOU ARE LOOKING AT ALL CELLS
GIVING INPUT TO THAT PARTICULAR
REGION INSTEAD OF PARSING OUT IF
THERE'S DIFFERENCES IN INPUTS
DEPENDING ON THE CELL TYPES THAT
RESIDE IN THAT REGION.
>> GREAT TO HAVE ADDITIONAL
SPECIFICITY AND ADDITIONAL TOOLS
FOR THE NEXT LEVEL ANALYSIS.
MICHELLE YOU WANT TO ASK THE
FOLLOW ON QUESTION TO MARIBELL.
HOW EASY IS TO COMBINE THE TOOL
SUCH AS CALCIUM IMAGING WHERE
YOU MAY BE ABLE TO RECORD
ACTIVITY AND THEN DO THE
TRACING?
ANY THOUGHTS ON THAT?
>> I WON'T SAY ANYTHING ABOUT
HOW EASY IT IS BUT I'LL TALK
ABOUT WHAT YOU CAN DO TO DO
THAT.
SO YOU CAN INSERT A GEN CAMP OR
OTHER SENSORS INTO THE RABIES
VIRUS AND DO THE TRACING AND ALL
THE TRACING WOULD BE EXPRESSED
IN A MARKER OF ACTIVITY AND THEN
YOU COULD RECORD THE CELLS.
THAT HAS ALREADY BEEN DONE
BEFORE BUT IF YOU WANT TO
TRANSCRIPTOMICALLY CLASSIFY THE
ACTIVITY YOU'D HAVE TO DO AN
ADDITIONAL STEP WHICH IS DOING
SPATIAL TRANSCRIPT OMICS AND
THEN ALIGN IT WITH TISSUE YOU
USED FOR YOUR ACTIVITY
RECORDINGS AND THAT HAS BEEN
DONE BY OTHER PEOPLE AND NOT
USING RABIES TRACING BUT USING
THINGS LIKE G CAMP AND
TRANSCRIPTOMICALLY LOOKING AT
THE CELLS.
>> LOTS TO DO HERE AND NO, NONE
OF THIS IS EASY.
WE ALL KNOW THAT BUT IT'S WORTH
MENTIONING WHAT YOU SEE IN THE
PAPER AND POSTER AND
PRESENTATIONS USUALLY REFLECTS A
LOT OF WORK AND A LOT OF
EXPERIMENTS THAT DIDN'T WORK
THAT YOU DON'T SHOW.
ALWAYS GOOD TO SEE KEEP THAT IN
MIND.
MICHELLE.
>> NEXT QUESTION IS FOR
CHRISTOPHER.
ARE THESE INFERRED LATENT
CIRCUITS CONFIRMED USING GROUND
TRUTH ACTIVITY IF AVAILABLE.
>> IT'S INFERRED.
IT'S INFERRED CONNECTIVITY FROM
RESPONSES.
OBVIOUSLY IN P.F.C. WE DON'T
HAVE THE GROUND TRUTH CONNE
CONNECTI
CONNECTIVITY.
CAN TRAIN ARTIFICIAL NEURAL
NETWORKS TO DO THE TASKS AND
HAVE CONNECTION TO THE MATRIX
AND TRY TO SEE WHAT THE LATENT
CONNECTIVITY STRUCTURE IS WE
INFERRED FOR THE HIGH
DIMENSIONAL SYSTEM AND IT EXISTS
IN THE HIGH DIMENSIONAL SYSTEM
IN A LATENT WAY.
PRECISELY IF YOU DO A CHANGE OF
BASIS ON THE RECURRENT MATRIX
THE STRUCTURE POPS OUT.
ANOTHER WAY TO THINK OF THAT IS
YOU'RE INFERRING IN THE SYSTEM
AND AS FAR AS VALIDATING TRUTH
WE CAN LOOK AT THE RNNs AND SEE
THE STRUCTURE DIRECTLY IN THE
RNN AND WE CAN EITHER DO CAUSAL
PERTURBATION TESTS WHERE WE
TRANSLATE LESIONS IN THE LOW
DIMENSIONAL CIRCUIT INTO LOW
RANK OR PATTERN CONNECTIVITY IN
THE HIGH DIMENSIONAL SYSTEM AND
CHECK THAT YOU GET THE PREDICTED
EFFECT ON BEHAVIOR.
SO THAT'S AS FAR AS AS BEST YOU
CAN DO FOR VALIDATION OF THIS
METHOD IN TERMS OF CONNECTIVITY.
>> IT SEEMS THE VALIDATION WILL
BE KEY LONG THE WAY.
>> THE LATENT CIRCUIT CAN BE
PERTURBED ON NODE OR CONNECTION.
NEURAL ACTIVITY AND DO YOU SEE
WHERE CONNECTOMICS DATA IS MORE
AVAILABLE.
IS THERE SOME GROUND TRUTH ABOUT
THE CONNECTS OR THE FUNCTIONAL
CONNECTIONS?
>> IN PRINCIPLE IT'S JUST
CONNECTIVITY THAT CAN BE DONE
THERE.
WHAT WE'VE ADDED IS THE NOTION
IS A SMALL CIRCUIT CAN BE
DISTRIBUTED ACROSS A SMALL
NUMBER OF NEURONS INSTEAD OF
BILINEAR DYNAMICS.
WHICH IS A CRITICAL STEP.
IN PRINCIPLE IT COULD BE APPLIED
AND WHAT WE HAD IN MIND WAS
FLEXIBLE BEHAVIOR.
>> ARE THERE MULTI-SENSORY
SECTORS YOU'RE STUDYING.
DO YOU SEE SEX DIFFERENCES?
WE'RE STUDYING THE CIRCUIT THAT
INTEGRATE THE INFORMATION AND
GOES DRIVE AND MODULATE THE
BEHAVIOR.
THAT'S A FEMALE SPECIFIC
BEHAVIOR AND IN TERMS OF THE
CIRCUIT ORGANIZATION WE MAP THE
CIRCUIT ORGANIZATION BACK BASED
ON DATA THAT COMES FROM FEMALE
SPECIFIC BRAINS.
SO THIS IS AN NF2.
ONE SOURCE OF THIS KIND OF DATA
IS CALLED FLY WIRE AND THIS IS
AND WE HAVE A COLLABORATION AND
THE OTHER MAIN RESOURCES AND
BOTH ARE FEMALE FLY BRAINS.
SO ALL THE ACTUAL DATA WE'VE
GOTTEN AND THE BEHAVIOR WE'RE
STUDYING IS FEMALE HOWEVER, AT
THE NODES OF INTEGRATION WHERE
THESE TWO MODALITIES ARE
CONVERGING, THOSE NODES ARE
KNOWN TO BE SEXUALLY DIMORPHIC
AND LET TO THE PROJECT.
THEY'RE OFTEN HOMEOLOGIES AND IF
WE SEE CONNECTION IN THE FEMALE
BRAIN THERE'S ANALOG IN
ORGANIZATION AND SOMETIMES
THERE'S DIFFERENT NUMBERS AND
SOMETIMES THERE'S OTHER
DIFFERENCES.
SO IT'S DEFINITELY PLAUSIBLE
THAT THESE TWO MODALITIES ARE
SIMILARLY COMING TOGETHER IN THE
MALE BRAIN IN A SIMILAR
ORGANIZATION TO DRIVE A MALE
SPECIFIC BEHAVIOR OR SOMETHING
GOING ON SIMILARLY WITH THE MALE
AND THOSE WOULD BE EXCITING TO
LOOK AT AND TO LOOK AT THE
DIFFERENCES BETWEEN THE TWO
SEXES ESPECIALLY ONCE WE GET
MORE INFORMATION ABOUT THE MALE
CONNECTOME AND WITH OTHER TOOLS
WE HAVE AVAILABLE IN THE FLY.
THANKS.
>> I WAS WONDERING, YOU TALKED
ABOUT THE FUTURE.
HOW CLOSE ARE WE TO GETTING THIS
REAL-TIME SETTINGS AND THESE
COIL ADJUSTMENTS TO REALLY BEING
HELPFUL IN THE ACTUAL CLINIC?
WHERE DO YOU THINK WE'RE AT
REALISTICALLY?
>> I THINK WE'RE CLOSE TO MAKING
THAT POSSIBLE ONCE WE CAN MODEL
DIFFERENT CONDITIONS IN REAL
TIME.
AND MAKING SURE WE COMBINE THE
TECHNIQUES TO DIFFERENT TYPES OF
COIL PARAMETERS LIKE
ORIENTATIONS YOU CAN USE IN
DIFFERENT STIMULATION CONDITIONS
AND MAKING SURE IT'S A LARGE
VARIETY OF NEURAL ANATOMY AND
NAVIGATE DIFFERENT SYSTEMS IN A
CLINICAL SETTINGS TO DO
OPTIMIZATION IN CLINICS WHICH IS
EASY AND BENEFICIAL TO PROMOTE
DEVELOPMENT AND PERSONALIZED
STIMULATION PROTOCOL.
WE'RE CLOSE.
I THINK IT WILL BE IN THE NEXT
YEAR OR TWO AND HOPEFULLY I'LL
GET TO BE PART OF THE WAVE OF
THE FUTURE.
>> IN DEALINGS WITH THE COMPLEX
DISORDER NOT THAT ANYTHING IN
THE BRAIN ISN'T COMPLEX BUT WHAT
WE'RE STARTING TO SEE WITH THE
DIFFERENT MODALITIES WITH THE
ABILITY TO OBTAIN BIOMARKERS AND
ANALYZE DATA ON THE FLY EVEN IT
WILL BE POSSIBLE TO INDIVIDUAL
I'D TREATMENT TO MAKE THEM MORE
EFFECTIVE.
THIS IS EXCITING FOR THE COMING
YEARS.
THERE'S A GENERAL QUESTION FOR
EVERYBODY HERE MAYBE IF WE HAVE
A FEW MINUTES FOR YOU ALL TO
CHIME IN.
THAT IS THE WORK WE HEARD ABOUT
TODAY REPRESENTS STUDIES ACROSS
A WIDE RANGE OF MODEL SYSTEMS.
THE HUMAN IS A GREAT MODEL
SYSTEM FOR UNDERSTANDING THE
HUMAN SYSTEM AND WE NOT ONLY
NEED TO TRANSLATE BUT LEARNING
WHAT WE CAN FROM HUMANS CAN
INFORM HOW WE STUDY ANIMAL
MODELS.
ARE YOU EXCITED ABOUT EXTRACTING
THROUGH COLLABORATION.
FROM THE TRAINING AND TALKS FROM
TODAY CAN YOU THINK OF
COLLABORATIONS INCLUDING HUMAN
AND NON-HUMAN SYSTEMS?
>> I THINK IT WILL BE A KEY
COMPONENT OF MOVING TO THE
FUTURE AND HAVE THE PERSPECTIVE
TO SEE WHERE IS INFORMATION
ABOUT THE BASIC FUNCTIONING OF
THE BRAIN CAN GUIDE US IN THE
CLINICAL REALM AND TAKING IT
BACK AND FORTH.
I THINK THAT CAN HELP
COLLABORATIONS ACROSS MODEL
SYSTEMS THAT ARE ABLE TO GET A
DIFFERENT FACET OF AND HAVE A
CHANCE TO PUT THAT TOGETHER IF
WE WORK TOGETHER.
>> THERE'S CELL TYPES LIKE IN
THE HUMAN BRAIN AND IMPORTANT TO
SEE WHAT REPLICATED FROM MONKEY
AND FINALLY TO HUMANS.
>> IT DOESN'T REPLICATE AND WHAT
HES -- WHAT'S COOL IS TO FIGURE
OUT WHAT'S DIFFERENT AND FIGURE
OUT WHY PEOPLE ARE IN SCIENCE.
ANY FINAL THOUGHTS?
WE'RE ON TIME HERE.
>> LET ME CONGRATULATE YOU ALL
FOR THE GREAT WORK YOU'VE DONE
FOR SPECTACULAR PRESENTATIONS
AND HOPEFULLY WE'LL GET TO
RECONVENE AGAIN AND THREE
DIMENSIONS AND MAY LEAD TO MORE
COLLABORATIONS AMONGST SOME OF
YOU OR ALL OF YOU.
CONGRATULATIONS AGAIN.
>> CONGRATULATIONS.
TO THINK THIS AMOUNT OF WORK AND
PRODUCTIVITY ALL HAPPENED
PROBABLY DURING THE PANDEMIC AS
WELL YOU SHOULD FEEL PROUD OF
YOUR ACCOMPLISHMENTS.
YOU'RE DOING GREAT WORK AND
WE'RE REALLY EXCITE.
YOU'RE THE FUTURE OF THE SPACE
SO WE APPRECIATE YOU ALL.
>> KEEP IT UP AND DON'T FORGET
TO LOOK TOWARDS THE BRAIN
INITIATIVE FOR FUTURE FUNDING IN
THE NEXT STEP OF YOUR SCIENTIFIC
JOUR
JOURNEY.
>>HELLO AND THANK YOU FOR
JOINING US.
TODAY IN THE FIRST HALF HOUR
WE'RE GOING SCREEN THE BRAIN
MAPPERS A 2022 SILVER TELLY
AWARD WINNING FILM.IN THE SECOND
HALF HOUR WE'LL DISCUSS THE
MAKING OF THE FILM WITH SEVEN OF
THE EIGHT RESEARCHERS WHO STAR
IN IT.
WE INVITE YOU TO POSE QUESTIONS
AND COMMENTS AND YOU CAN TYPE
THEM IN THE Q&A BOX AS WE
PROCEED.
MY NAME IS CAROLYN ALBERT.
I'M THE PROJECT'S P.I. AND
EXECUTIVE PRODUCER.
WHAT LIT THE SPARK FOR ME WAS A
TALK GIVEN AT THE 2019 NSF NANO
SCALE SCIENCE AND ENGINEERING
AND GRANTEES MEETING.
JEFF GAVE A TALK ABOUT THE
DAUNTING TASK OF MAPPING THE
CIRCUITRY OF THE BRAIN WITH NANO
SCALE PRECISION AND HOW THAT
MIGHT ADVANCE OUR UNDERSTANDING
OF MIND AND BEHAVIOR.
FOR ME, THIS WAS A GRAND
CHALLENGE WORTHY OF SHARING WITH
BROADER AUDIENCES BUT ENGAGING
THE AUDIENCES WOULD BE TRICKY.
HOW DO YOU SHARE A STORY LIKE
THIS ONE WITH PEOPLE WHO MAY NOT
BE ALL THAT FAMILIAR WITH BRAIN
ANATOMY, NEUROSCIENCE, ELECTRON
MICROSCOPY AND BIG DATA,
ALGORITHMS AND A.I.?
I BROUGHT ON NOVA FILMMAKER
LARRY KLINE TO FIGURE OUT AN
APPROACH.
SOON WE FACED AN ADDITIONAL
CHALLENGE, THE PANDEMIC LOCK
DOWN.
WE POSTPONED FOR A YEAR AND THEN
HAD TO GO AHEAD USING A MIX OF
REMOTE PRODUCTION TECHNIQUES AND
AS YOU WATCH SEE IF YOU CAN TELL
WHICH PARTS WERE FILMED
REMOTELY.
LET'S ROLL.
WE WELCOME YOUR COMMENTS AND
QUESTIONS IN THE Q&A BOX.
THANK YOU AND ENJOY.
>> IT'S OUR REMARKABLE BRAINS
THAT ENDOW US WITH ABILITY AND
EMPOWER OUR THOUGHTS AND ACTS
AND RESPONSIBLE FOR EVERYTHING
WE SENSE, FEEL, DISCOVER AND
REMEMBER.
>> THE BRAIN IS WHAT ALLOWS US
TO MAKE SENSE OF THE WORLD.
>> AND PERHAPS MOST IMPORTANTLY,
OUR BRAINS GIVE US THE ABILITY
TO UNDERSTAND, CREATE AND DO
PREMARKABLE THINGS.
>> -- REMARKABLE THINGS.
BUT EXACTLY HOW OUR BRAINS GIVE
US ANY OF THESE ABILITIES HAS SO
FAR DEFIED SCIENTIFIC
EXPLANATION.
>> THE BRAINS WE KNOW NEXT TO
NOTHING AND THAT MAKES IT QUITE
DIFFERENT FROM OTHER ORGAN
SYSTEMS WHERE NO ONE WOULD SAY
WE KNOW NEXT TO NOTHING ABOUT
THE HEART.
WE CAN REPLACE A PERSON'S HEART
WITH AN ARTIFICIAL HEART.
>> IN PHYSICS WE'VE BEEN ABLE TO
NOT ONLY UNDERSTAND WHAT ATOMS
ARE MADE OF WE KNOW HOW GALAXIES
MILLIONS OF LIGHT YEARS AWAY
BEHAVE AND HOW IS IT BETTER WE
CAN BETTER UNDERSTAND THE
UNIVERSE THAN THE BRAIN.
>> WE MAY BE ON A PATHWAY FOR
UNDERSTANDING OUR BRAINS IN WAYS
THAT HAVE ALLUDED SCIENTISTS AND
PHILOSOPHERS FOR CENTURIES.
COULD A COMPREHENSIVE MAP OF THE
VAST NETWORK OF BRAIN CELLS
CALLED NEURONS BECOME THE
STARTING POINT FOR UNLOCKING THE
MYSTERIES OF THE BRAIN?
WE'RE NOT TOTALLY IN THE DARK
ABOUT HOW OUR BRAINS WORK.
BY ILLUMINATING BRAIN ACTIVITY
AND MRIs AND OTHER IMAGING
SYSTEMS HAVE ENABLED US TO LOOK
AT HOW WE PROCESS INFORMATION
LIKE SMELL, VISION AND TOUCH.
EXERT MOTE ER CONTROL AND SOLVE
PROBLEMS OR PROCESS MUSIC,
LANGUAGE AND MUCH MORE.
BUT WHAT WE CAN'T SEE ON MRIs
ARE THE SUPER THIN NEURON
NETWORKS THAT FACILITATE ALL OF
OUR THOUGHTS AND ACTIONS.
INDIVIDUAL NEURONS IN THESE
NETWORKS ARE SO SLENDER YOU CAN
ONLY SEE THEM UNDER MUCH HIGHER
RESOLUTION.
ONLY THEN DO THEIR UNIQUE SHAPES
REVEAL HOW SPECIALIZED THEY ARE
AMONG ALL THE CELLS IN THE BODY.
NEURONS RECEIVE INFORMATION IN
THE FORM OF IMPULSES THROUGH
THEIR LOOP LIKE BRANCHES CALLED
DENDRITE AND SEND THAT
INFORMATION VIA AXONS TO OTHER
NEURONS.
SO NEURONS ARE THE BUILDING
BLOCKS OF A REMARKABLE
COMMUNICATION SYSTEM THREADING
THROUGHOUT OUR BODIES AND
CENTERED IN OUR BRAINS.
>> SO EACH CELL IS PART OF A
TWITTER UNIVERSE, IF YOU WILL.
IT'S RECEIVING LOTS OF
INFORMATION ON THE DENDRITES AND
FROM THAT INFORMATION IT DECIDES
WHAT IS NEWS WORTHY AND THEN IT
SENDS THAT INFORMATION OUT TO
ALL OF ITS LISTENERS AND THAT'S
TRUE OF EVERY CELL OF THE
HUNDREDS AND HUNDREDS OF
MILLIONS OF CELLS IN THE BRAIN.
>> AND THIS VAST NETWORK OF
NEURONAL CELLS IS CONNECTED BY
TRILLIONS OF CELLULAR JUNCTION
POINTS CALLED SYNAPSES.
>> THE SYNAPSE.
IT'S A PLACE WHERE AN AXON
RELEASES A CHEMICAL CALLED A
NEUROTRANSMITTER THAT ACTIVATED
A RECEPTOR SET ON THE DENDRITE
OF ANOTHER NERVE CELL.
>> SYNAPTIC CONNECTIONS CAN
WEAKEN OR STRENGTHEN OVER TIME.
SO BESIDES RELAYING AND
PROCESSING INFORMATION, SOME
EXPERTS BELIEVE THEY MAY ALSO
STORE INFORMATION LIKE OUR
MEMORIES.
>> MEMORIES ARE PROBABLY STORED
IN THE PATTERNS OF SYNAPSES THAT
WERE ACTIVATED AT THE TIME THEY
WERE FORMED.
NOT ALL MEMORIES ARE NECESSARILY
STORED.
IN FACT IT'S IMPORTANT
EVERYTHING IS STORED OTHERWISE
YOUR BRAIN WOULD GET FILLED UP.
>> IT SEEMS LIKE OUR BRAINS ARE
ALREADY FILLED UP AND CONTAIN
BILLIONS OF THREAD-LIKE NEURONS.
SO MANY IF WE PLACED EACH STRAND
END TO END.
>> IT LOOKS LIKE IT WOULD GO
FROM HERE TO THE MOON.
AND POSSIBLY BACK.
I'M NOT SURE ABOUT THE BACK
PART.
>> THIS NEURON JUNGLE IS SO
DENSE AND CROWDED IT'S ALMOST
IMPOSSIBLE TO PINPOINT THE
NEURONAL NETWORKS ASSOCIATED
WITH A GIVEN THOUGHT OR ACTION.
>> AND THIS LACK OF KNOWLEDGE
HAS BEEN A MAJOR STUMBLING BLOCK
FOR DECODING THE BRAIN.
>> IT'S LIKE OUR BRAIN IS A MAP
WHERE WE KNOW THE LOCATION OF
LANGUAGE AND MUSIC CITIES, MOTOR
CONTROL AND OTHER TOWNS.
BUT CAN'T SEE THE ROADS THAT
CONNECT THEM OR THE ROADS IN AND
AROUND THEM.
>> SO THE IDEA WE ARE CONTINUING
TO TRY AND WADE THROUGH THE
BRAIN TO UNDERSTAND HOW THESE
NETWORKS ARE PROCESSING
INFORMATION WITHOUT EVEN THIS
MAP SEEMS LIKE IT'S NOT THE MOST
EFFICIENT WAY TO PROCEED.
>> THAT'S WHY MANY
NEUROSCIENTISTS BELIEVE IF WE
REALLY WANT TO FIGURE OUT THE
BRAIN, WE NEED TO START BY
CREATING A KIND OF NEURONAL ROAD
MAP CALLED A CONNECTOME.
>> SO THIS INCREDIBLE KIND OF
SPIDER'S WEB OF HOW EVERY NEURON
CONNECTS TO OTHER NEURON IF YOU
MAPPED IT THAT WOULD BE THE
CONNECTOME.
>> BUT WITH BILLIONS OF CELLS IN
THE ENDLESS FOREST, HOW DOES ONE
EVEN BEGIN?
>> TO MAP THE BRAIN REQUIRE
SOMETHING AT LIKE NANO SCALE
IMAGING.
>> WHICH MEANS STARTING WITH
THIN SLICES OF A BRAIN AND IM
IMAGING THEM IN AN ELECTRON
MICROSCOPE AND TINY PIECES OF
BRAIN TISSUE CAN BE COLLECTED
FOR ANALYSIS.
BUT A HUMAN BRAIN IS SO LARGE
AND THE NEURAL NETWORK SO VAST,
ATTEMPTING A HUMAN BRAIN
CONNECTOME IS FOR NOW A BRIDGE
TOO FAR.
SO RESEARCHERS ARE STARTING WITH
THE BRAINS OF MICE AND OTHER
ANIMALS TO SEE IF THEY CAN MAKE
CONNECTOMES AND WHAT THEY MIGHT
LEARN FROM THEM.
BUT EVEN SMALL BRAINS ARE HUGE
CHALLENGES.
>> ANIMALS LIKE THE FLY HAS
ABOUT A MILLION NEURONS.
THE MOUSE, HAS ABOUT 100 MILLION
NEURONS.
>> SO IS CREATING ANY CONNECTOME
EVEN POSSIBLE?
>> TRUTH BE TOLD IT'S HARD TO
GET A CONNECTOME.
IN FACT THERE'S ONLY A FEW
CONNECTOMES THAT HAVE EVER BEEN
GOTTEN AND MOSTLY OF TEENY WEENY
LITTLE ANIMALS LIKE WORMS THAT
ONLY HAVE 300 NERVE CELLS.
>> THIS TINY NEMATODE WORM IS
CALLED C. ELEGANS.
IN THE 1970s, CAMBRIDGE
UNIVERSITY MOLECULAR BIOLOGIST
JOHN WHITE AND SIDNEY BRENNER
TRIED A NEMATODE EXPERIMENT.
>> THE CAME UP WITH THE IDEA WE
NEEDED A CONNECTOME TO
UNDERSTAND HOW THE BRAIN WORKED
AND PICKED THE BRAIN OF A WORLD
A C. ELEGANS WITH ONLY 302
NEURONS.
THE CAMBRIDGE TEAM THINLY SLICE
THE WORMS AND FILMED THE SLICE
MOUNTED ON AN ELECTRON
MICROSCOPE.
THEY THEN PRINTED OUT LARGE
PHOTOGRAPHS AND USED COLORED
PENS TO TRACE THE NEURON PIECES
THEY SAW IN EACH SLICE UNTIL
THEY HAD EVERY NEURON MAPPED.
IT TOOK NEARLY A DECADE BUT IN
1986, C. ELEGANS WITH THE MERE
302 NEURONS BECAME THE FIRST AND
TO THIS DAY ONLY ORGANISM WITH A
FULLY MAPPED CONNECTOME.
>> C. ELEGANS WAS GREAT BUT IT'S
NOT HIGHLY INTELLECTUALLY
CAPABLE AND THE BRAIN IS SIMPLE.
EVEN THE MOUSE BRAIN HAS 10,000
TIMES THE NEURONS.
AND CAPABLE ANIMALS WE ALL WANT
TO UNDERSTAND WE DON'T HAVE
ANYWHERE NEAR THAT TECHNICAL
CAPABILITY TO TACKLE THAT.
>> THINK OF WHAT 300 MILLION
CELLS REQUIRE IT WOULD BE 10
MILLION YEARS SO NOBODY WOULD DO
THAT EXPERIMENT.
>> WE REALIZED THE ONLY WAY IT
WAS POSSIBLE WAS TO AUTOMATE HOW
WE TAKE THE IMAGES AND
ALGORITHMS THAT AUTOMATE NEURONS
AND TRACE THE CONNECTIONS AND
MAKE THE ENTIRE THING DIGITAL.
>> OVER THE LAST FEW DECADES
THAT'S WHAT RESEARCHERS DID
WORKING ON MANY NEURONAL MAPS
FROM PIECES OF VARIOUS ANIMAL
BRAINS.
THEY BEGIN WITH A TINY BRAIN
SAMPLE STAINED WITH A METALLIC
LIQUID ENCASED IN PLASTIC AND
MOUNTED ON A TRUCK ACROSS A
KNIFE THAT SLICES IT.
THE SUPER THIN SLICES GO ON A
CONVEYOR BELT AND ULTIMATELY TO
ELECTRON MICROSCOPES.
THE IMAGES ARE FED THROUGH A
COMPUTER THAT RESTACKS THE
SLICES IN THE ORIGINAL SAMPLE
ONLY NOW WITH THE NEURONS
CLEARLY OUTLINED.
ANOTHER PROGRAM ISOLATES THEM BY
COLOR AND BEGINS TO FULLY RENDER
THEM.
HERE WE SEE THE RED DENDRITE OF
ONE NEURON AND THE GREEN AXON OF
ANOTHER.
THE COMPUTER WILL RETURNED ALL
THE NEURONS IN THE SAMPLE THE
SAME WAY
>> IT REVEALS SOMETHING YOU HAVE
KNOWN WAS THERE BUT YOU COULD
NEVER SEE BEFORE.
>> THESE NEURON IMAGES FROM A
MOUSE BRAIN CREATED ALMOST A
DECADE AGO BY JEFF LICHTMAN'S
LAB AT HARVARD ALSO PRESENTED A
FORMIDABLE REALITY CHECK.
>> WE COMPLETELY RENDERED EVERY
SINGLE ITEM IN THIS TINY WEENY
CYLINDER.
IT WAS FANTASTICICALLY BEAUTIFUL
TO SEE AND ALSO SO MUCH MORE
COMPLICATED THAN ANYTHING I HAD
EVER SEEN BEFORE.
I DEPAIRED A LITTLE BIT SEEING
HOW SMALL YOU HAVE ACTUALLY MADE
RELATIVE TO BIG QUESTIONS LIKE
DOING A WHOLE MOUSE BRAINS
CONNECTOME.
>> IF IT WASN'T CLEAR BEFORE IT
WAS NOW.
CREATING A FULL CONNECTOME FOR
EVEN A MOUSE SIZE BRAIN WOULD
REQUIRE A MASSIVE EFFORT.
>> IT WAS AGAIN TIME TO THINK
SMALL.
THE BRAIN OF A DROSOPHILA FRUIT
FLY IS THE SIZE OF A POPPY SEED
ON A BAGEL.
YET IT CONTAINS ABOUT 100,000
NEURONS AND MILLIONS OF SYNAPTIC
CONNECTIONS.
BUT IN 2020 RESEARCHERS AT THE
HOWARD HUGHES MEDICAL INSTITUTE
GENELIA RESEARCH CAMPUS
ANNOUNCED THEY MAPPED THE FLIES
HELP BRAIN.
THIS IS -- HEMI BRAIN.
THIS IS THE OUTLINE AND THESE
IMAGES SHOW SOME OF ITS 25,000
NEURONS.
THOUGH RESEARCHERS STILL HAVE
MORE THAN HALF A BRAIN TO GO,
THESE PARTIAL MAPS TOGETHER
COMPRISE THE LARGEST CONNECTOME
EVER PRODUCED.
>> SEEING THE CONNECTOME FOR THE
FIRST TIME IT WAS ABSOLUTELY
BREATHTAKING.
YOU ONCE FEEL HOPE THAT YOU CAN
ACTUALLY SEE THE REALITY OF THIS
COMPLEXITY AND MAYBE AS A
SCIENTIST A LITTLE BIT OF WORRY
OR DESPAIR AT HOW CHALLENGING IT
IS TO UNRAVEL THE FUNCTION OF
THAT MASS, EVEN FOR A FRUIT FLY.
>> REACHING THIS MILESTONE HAS
BEEN THE DREAM OF THE PROJECT'S
FOUNDER AND GUIDING SPIRIT,
JERRY RUBIN.
>> I HAD TO CONVINCE THE PEOPLE
IN MY ORGANIZATION THAT THIS IS
WORTH DOING.
IT WAS A 10 YEAR INVESTMENT OF
TENS OF MILLIONS OF DOLLARS.
SO I LOST A LOT OF SLEEP LIKE,
I'M GOING TO LOOK REALLY BAD IF
THIS FAILS.
>> THE GENELIA FLY TEAM
DEVELOPED NEW METHODS FOR
PREPARING SAMPLES AND AUTOMATING
THE SYSTEM.
THEY BEGAN USING FOCUSED ION
BEAM MICROSCOPES.
THESE CAN WHISK OFF AN IMAGE THE
NANOTHIN LAYERS ALMOST
SIMULTANEOUSLY.
THE MACHINES OPERATE
AUTOMATICALLY AND CONTINUALLY AS
LONG AS SAMPLES REPLENISH AND
ALL THIS SPEEDED THINGS UP
CONSIDERABLY.
>> EVERYTHING IS BEING DONE BY Y
COMPUTER INSTRUCTION. EVERY
TIME HUMANS GET INVOLVED IT
SLOWS THINGS DOWN.
>> THOUGH GENELIA MACHINES
TURNED OUT HUNDREDS OF THOUSANDS
OF 2D IMAGE, TO RENDER THEM INTO
3 DIMENSIONAL NEURONS REQUIRED
MASSIVE AMOUNTS OF DATA
PROCESSING.
>> GENELIA WENT TO A WORLD
LEADER IN DATA PROCESSING FOR
HELP.
>> GOOGLE NOT ONLY AGREED TO
PARTNER WITH GENELIA, THE
COMPANY DECIDED TO DO THE
COMPUTATIONAL WORK FOR FREE.
THE OBVIOUS QUESTION WHAT
MOTIVATED GOOGLE TO MAKE SUCH A
COMMITMENT?
>> THIS WAS AREA IN WHICH BEST
COMPUTER SCIENCE COULD MAKE A
DIFFERENCE.
SO THE IDEA OF TAKING THESE VERY
LARGE THREE DIMENSIONAL DATA
SETS, RECONSTRUCTING THEM
ANNOTATING THEM, THIS IS THE
TYPE OF PROBLEM THAT GOOGLE
DEVELOPED EXPERTISE IN THROUGH
WORKING ON THINGS LIKE GOOGLE
MAPS AND GOOGLE EARTH.
IT PRESENTED NEW CHALLENGES AND
WE WANT TO MAKE COMPUTERS
SMARTER.
>> GOOGLE NEEDED TO ADAPT
ALGORITHMS USED FOR OBJECT AND
PATTERN RECOGNITION TO SEE IF
THESE COULD RECOGNIZE NEURONS.
THEY BEGAN BY FEEDING THEIR
MACHINES PRECISE NEURONAL
IMAGES, SUPPLIED BY GENELIA SO
THE MACHINES CAN TRAIN
THEMSELVES ON WHAT TO LOOK FOR.
>> THE MACHINES ALSO RELY ON
ARTIFICIAL NEURAL NETWORKS THAT
MIMIC THE WAY NEUROSCIENTISTS
BELIEVE THE BRAIN PROCESSES
VISUAL RECOGNITION AND ANIMALS
LIKE THESE MICE.
>> WHAT THEY FOUND WAS THAT THE
BRAIN HAD ONE LAYER OF CELLS
WHICH THEY CALL SIMPLE CELLS,
AND THESE WOULD RESPOND TO
ORIENTED GRAINS OF LIGHT AND
THEN YOU HAD ANOTHER LAYER OF
NEURONS THEY ALSO DISCOVERED IN
THE BRAIN OF THESE ANIMALS
CALLED COMPLEX CELLS.
AS LONG AS ONE OF THE SIMPLE
CELLS RESPONDS TO THIS FEATURE,
THE COMPLEX CELLS RESPOND ALSO.
AND YOU CAN COMBINE THESE LAYERS
TO GET PROGRESSIVELY MORE
COMPLEX AND HIGHER LEVEL
REPRESENTATIONS OF ANY IMAGE.
>> MACHINE MODELS OF THESE
VISUAL PROCESSING SYSTEMS ARE
CALLED CONVOLUTIONAL NEURAL
NETWORKS.
AND THEY ARE TODAY A CORNERSTONE
OF ARTIFICIAL INTELLIGENCE.
>> EVEN SOMETHING LIKE A SELF
DRIVING CAR WHICH MIGHT HAVE A
CAMERA IN THE FRONT OF IT AND IS
LOOKING AT A VISUAL SCENE AND
TRYING TO FIGURE OUT WHERE IS
THE ROAD, WHERE IS THE STOP
SIGN, IS THERE A TRAFFIC LIGHT?
THOSE DECISIONS ARE OFTEN BEING
MADE BY SOME TYPE OF C CONVOLUTL
NEURAL NETWORK.
>> NEURONS HAVE COMPLEX SHAPES
SO VERIAN JAIN HAD TO DEVELOP
EQUALLY COMPLEX VERSION OF
GOOGLE'S RECOGNITION ALGORITHM.
>> IF I CAN PICK A POINT IN THE
IMAGE AND THE ALGORITHM STARTS
TO TRY TO FIGURE OUT WHAT ARE
THE BONDRIES OF THE OBJECT
ASSOCIATED WITH THAT POINT YOU
PICKED.
FROM THAT POINT THE AL FOR
RHYTHM IS LOOKING AROUND AND
DECIDING WHAT ELSE IS PART OF
THAT OBJECT?
SO WHAT YOU ARE SEEING AS THAT
POINT MOVES AROUND IS THE
ALGORITHM PROGRESSIVELY
EXPANDING ITS FIELD OF VIEW SO
IT'S STARTING IN ONE PLACE AND
MOVING OVER HERE AND SAYING OKAY
WHAT ELSE IS PART OF THE OBJECT?
IT IS EXPANDING THE SHAPE AS IT
GOES ALONG.
>> THOUGH THE SYSTEM IS
EXTRAORDINARY IT CAN STILL MAKE
MISTAKES.
THE COMPUTER ANALYSIS IS GREAT.
BUT IT IS NOT PERFECT.
SO WHAT WE NEED TO DO IS REVIEW
IT WITH HUMANS.
AND THE HUMANS LOOK AT IT AND
THEY SAY OH, THESE THINGS ARE
JOINED TOGETHER AND THEY
SHOULDN'T BE TOGETHER.
WE HAVE A FRANKEN BODY WE LIKE
TO CALL THEM.
>> IN THIS FRANK ENBODY THE
COMPUTER SEES ONE NEURON BUT IT
IS REALLY TWO.
IT TOOK SCORES OF GENELIA
PROOFREADERS YEARS TO CORRECT
THE MISSAKES BUT AS -- MISTAKES
BUT AS THEY DID THE NEW
INFORMATION WENT BACK TO GOOGLE
AND THE ALGORITHMS KEPT GETTING
BETTER.
JERRY RUBIN NOW SAYS IT WILL
TAKE A AREA OR TWO TO FINISH THE
FLY CONNECTOME WHICH WOULD COME
IN UNDER HIS ORIGINAL ESTIMATE.
BUT DESPITE THE COMING
MILESTONE, THIS IS AFTER ALL A
FLY BRAIN WE ARE TALKING ABOUT.
WHAT COULD ITS CONNECTOME
POSSIBLY TELL US ABOUT THE HUMAN
BRAIN?
>> IT TURNS OUT THAT FRUIT FLY
BRAINS ARE MADE OF EXACTLY THE
SAME COMPONENTS THAT OUR BRAINS
ARE.
THESE NEURONS.
AND THEY ACTUALLY TALK TO EACH
OTHER THE SAME WAYS EXCHANGING
CHEMICALS AND EXCITING ONE
ANOTHER AS IT WERE TO PASS ON
INFORMATION.
SO IF WE CAN UNDERSTAND THE
BUILDING BLOCKS OF THAT
COMMUNICATION IN A FLY'S BRAIN,
THAT APPLIES TO OUR BRAINS AS
WELL.
>> GWYNETH CAR LEADS A GENELIA
TEAM TO EXPERIMENT WITH FRUIT
FLIES TO UNDERSTAND HOW THEIR
BRAINS REACT TO THINGS IN THEIR
ENVIRONMENT THAT MOTIVATE
BEHAVIOR.
>> WE TRY TO STUDY REALLY
FUNDAMENTAL BEHAVIORS, THAT OUR
BRAINS ALL EVOLVE TO BE ABLE TO
DO.
THESE ARE THINGS LIKE EATING,
SLEEP, OR IN THE CASE OF MY LAB
IN PARTICULAR, HOW TO NOT BE
EATEN.
WE ARE INTERESTED IN HOW A FRUIT
FLY EVADES BEING EATEN BY
PREDATORS THAT TRY TO CAPTURE
THEM.
WHAT WE LEARNED FROM OUR
RESEARCH IS THAT EVEN FLIES ARE
CAREFULLY CONSIDERING A STRATEGY
FOR ESCAPE.
IT CAN DO A FASTER TAKE OFF
WHERE IT DOESN'T RAISE ITS
WINGS, IT JUST JUMPS OFF THE
GROUND OR DO A SLOWER KIND OF
TAKE OFF WHERE IT DOES RAISE
WINGS AND SLOWLY DEPRESS THEM
AND GET OFF THE GROUND IN A
LONGER TIME.
AND WE UNDERSTAND NOW THE
NEURONS INVOLVED IN THE CHOICE
BETWEEN THOSE KINDS OF TAKE
OFFS.
>> FLIES AREN'T THE ONLY
CREATURES WITH QUICK ESCAPE
ABILITIES.
BUT WE DON'T KNOW WHICH NEURONS
IN OUR BRAINS MESSAGE SUCH
ACTIONS WHEREAS GWYNETH CARD'S
FLY TEAM CAN USE IMAGING
TECHNIQUES AND THE CONNECTOME TO
IDENTIFY THE NEURAL NETWORK
CONTROL ESCAPE BEHAVIOR.
>> WHAT THE CONNECTOME ALLOWED
US TO DO IS GO BEYOND THAT ONE
NEURON THAT INVOLVED IN SAY WHAT
IS THE NETWORK HERE?
HOW IS THAT NEURON GETTING
INFORMATION?
WHAT KIND OF INFORMATION IS IT
GETTING, WHAT IS THE ANIMAL
ACTUALLY TRYING TO UNDERSTAND
ABOUT THE WORLD, THAT WAS
VIRTUALLY IMPOSSIBLE TO DO IN A
COMPREHENSIVE AND SYSTEMATIC WAY
WITHOUT THE CONNECTOME.
>> BESIDES MAPPING AND TRACING
NEURONS, GENELIA'S CONNECTOME
PIN POINTS SYNAPSES.
SEEN HERE AS MICROSCOPIC DARK
SMUDGES IN THE RED CIRCLES, THAT
LINK NEURAL NETWORKS.
AND THIS IS HELPING OTHER
NEUROSCIENTISTS AS WELL.
>> THEY HAVE REVOLUTIONIZED THE
THINKING OF HOW CIRCUITS WORK IN
THE FLY BRAIN, IT IS NO LONGER
MODELING IT, YOU ACTUALLY KNOW
WHO IS CONNECTED TO WHOM.
ONCE YOU KNOW WHO IS CONNECTED
TO WHOM, YOU NO LONGER HAVE TO
TRY TO GUESS.
>> IN A RELATIVELY SHORT TIME WE
HAVE SEEN PEOPLE REALLY NOT ONLY
TAKE ADVANTAGE OF THE HEMI BRAIN
DATA SET BUT ALSO HAVING A
BROADER EFFECT IN NEUROSCIENCE
SHOWING THIS TYPE OF INFORMATION
ABOUT THE NERVOUS SYSTEM IS
REALLY QUITE FUNDAMENTAL AND CAN
BE EXTREMELY VALUABLE.
>> SUCCESS IN BUILDING A FLY
CONNECTOME HAS ENERGIZED ONGOING
EFFORTS BY SEVERAL RESEARCH
GROUPS TO PURSUE A FAR MORE
COMPLICATED MOUSE BRAIN
CONNECTOME.
THE ALLEN INSTITUTE FOR BRAIN
SCIENCE IN SEATTLE HAS BEEN A
MAJOR CONTRIBUTOR.
AND IN 2019 ANNOUNCED THAT AFTER
NEARLY A DECADE OF WORK IT HAD
IMAGED 100,000 NEURONS AND A
BILLION SYNAPTIC CONNECTIONS IN
A CUBIC MILLIMETER OF A MOUSE
BRAIN.
IT WAS A SIGNIFICANT SUCCESS.
BUT DAUNTINGLY THERE WERE STILL
499 CUBIC MILLIMETERS LEFT TO
MAP.
AS SEVERAL RESEARCH GROUPS
TRAVELED A LONG PATHWAY TO A
MOUSE CONNECTOME, OTHERS ARE
PURSUING AN INTERIM STEP.
BETWEEN THE MAMMALIAN BRAIN OF A
MOUSE AND A INVERTEBRATE LIKE
DROSOPHILA OR C ELEGANS, THERE
IS A WHOLE GROUP OF ANIMALS THAT
HAVE BACK BONES ABOUT WHICH
CONNECTOMICS COULD PROVIDE A LOT
OF INSIGHT AND PERHAPS NO ANIMAL
BETTER SUITED FOR THIS THAN THE
LARVAL ZEBRAFISH.
>> THE ZEBRAFISH WE SEE IN ARE
ADULTS.
CONNECTOMIC RESEARCHERS ARE
INTERESTED IN THEIR BABIES.
>> ZEBRAFISH I WORK WITH YOU
NEED A MICROSCOPE TO LOOK AT.
>> MARE YELL LA PETCOVA IS A
POST-DOC TRAIT NEUROSCIENTIST AT
HARVARD UNIVERSITY WHO USES
CONNECTOMICS TO STUDY THE BRAINS
OF ZEBRAFISH.
>> IT IS SURPRISINGLY SIMILAR TO
US, WE SHARE GENES, WE HAVE
SHARED THE COMMON ANCESTOR.
I THINK ABOUT 400 MILLION YEARS
AGO WE BOTH WERE SWIMMING
AROUND.
THEY START AS A SINGLE CELL AND
SEVEN DAYS LATER THEY HAVE
100,000 NEURONS AND IN THREE
DAYS IT ALREADY STARTS SWIMMING.
IMAGINE IN ONLY A WEEK YOU HAVE
TO BUILD A CIRCUIT THAT HUNTS,
THAT CAN TAKE IN THE INFORMATION
AROUND IT AND BUILD A MACHINE
WHICH CAN DO SUCH COMPLICATED
ACTION.
>> AND BECAUSE THEY ARE
TRANSPARENT, USING A MICROSCOPE
SHE CONCEIVED A NEURONAL
PATHWAYS INVOLVED IN ACTIONS
LIKE TAIL FLICKS, AND EVEN
MEASURE THEM.
>> YOU CAN PUT IN MOLECULE WHICH
TELLS YOU WHEN THE NEURON TURNS
ON.
AND SEE THE MOLECULES LIGHT UP
LIKE A LIGHT BULB.
>> THE CONNECTOME SHE IS
CREATING CAN HELP PINPOINT THE
FLICK NEURONS PRECISELY.
TO CREATE THEIR CONNECTOME, THE
LAB USES THE BASIC SLICING AND
IMAGING PROCEDURES AND HERE TOO
GOOGLE HELPS PROCESS THE IMAGES.
BUT MARIELA'S LAB HAS A UNIQUE
COMMUNITY OF CHECKERS.
>> WE BRING IN LOT OF PEOPLE TO
PROOFREAD.
WE BRING IN COLLEGE STUDENTS, WE
BRING IN POST DOCS, GRADUATE
STUDENTS, PROFESSORS, WE ALSO
BRING IN HIGH SCHOOL STUDENTS
AND I BROUGHT IN MY MOM.
MY MOM DOES ALL THE WORK FROM
HUNGAHUNGARY.
YOU CAN DO ALL THE WORK FROM
YOUR COMPUTER WITH CONNECTOMIC
AND YOU CAN BE ANYWHERE IN THE
WORLD.
CONNECTOMEICS HAS A HUGE
POTENTIAL FO FOR ENGAGEMENT FROM
THE PUBLIC.
>> IN A PAPILLAR INTERACTIVE
GAME CALLED iWIRE DEVELOPED BY
THE SUN LAB AT PRINCETON,
PLAYERS FROM ALL OVER THE WORLD
VIBE WITH EACH OTHER TO SEE WHO
CAN BEST RECONSTRUCT NEURONS IN
A MOUSE RETINA.
THE SITE ALSO TEACHES GAMERS
ABOUT THE INTRICACIES OF NEURONS
AND SYNAPSES AND HIGH WIRE CAN
CLEARLY BECOME A TRAINING GROUND
FOR CITIZEN PROOFREADERS WHICH
WOULD CERTAINLY HELP WITH THE
MASSIVE TASK OF COMPLETING A
MOUSE CONNECTOME.
ALTHOUGH A MOUSE BRAIN IS A
THOUSAND TIMES SMALLER AND FAR
LESS COMPLICATED THAN A HUMAN
BRAIN, AS MAMMALS THEIR BRAINS
WILL BE FUNDAMENTALLY LIKE OUR
OWN AS ARE MANY OF THEIR
BIOLOGICAL SYSTEMS.
THE MOUSE IS PROBABLY THE MOST
POPULAR ANIMAL FOR STUDY IN
BIOLOGY.
NOT THE LEAST OF WHICH IS
DISEASES THAT HAVE CORRELATES TO
HUMAN DISEASE ARE BEING MADE IN
MICE ALL THE TIME.
SO THERE ARE CARDIOVASCULAR,
DIABETIC, ALZHEIMER'S, MICE TO
NAME A FEW.
AND MANY OF THESE ARE
NEUROLOGICAL DISEASES.
LIKE RHETT'S SYNDROME AND AUTISM
SPECTRUM DISORDER.
THESE ANIMALS PROVIDE AN
OPPORTUNITY TO LOOK AT THE
BRAINS OF ANIMALS THAT HAVE
COGNITIVE PROBLEMS THAT ARE
SIMILAR TO DISEASES THAT HUMANS
HAVE.
>> BECAUSE MOUSE BRAINS ARE
CLOSER TO OURS, SHORT OF A HUMAN
BRAIN RIGHT NOW THEIR CONNECTOME
WOULD BE THE ULTIMATE PRIZE.
BUT TO DO THIS THE COST FOR DATA
PROCESSING ALONE WOULD BE WELL,
MIND BOGGLING.
IF YOU TOOK ALL THE MATERIAL
THAT LIVES IN THE LIBRARY OF
CONGRESS, NOT JUST THE BOOKS BUT
ALL THE AUDIO, ALL THE VIDEO,
EVERY MOVIE, EVERY SONG THAT HAS
EVER BEEN WRITTEN AND YOU PILED
IT ALL TOGETHER AND SAID HOW
MUCH DATA IS THAT AND THEN YOU
ASK HOW MUCH DATA A MOUSE BRAIN
WOULD BE, A MOUSE BRAIN MIGHT BE
SOMETHING LIKE A HUNDRED TO
1,000 TIMES MORE DATA THAN IT'S
EVER BEEN COLLECTED ALTOGETHER
IN HISTORY OF HUMANITY.
THAT WOULD BE A AMOUNT OF DATA
CALLED AN EXBITE OF DATA WHICH
IS A THOUSAND PEDABYTES OF DATA
WHICH IS A MILLION TERABYTES OF
DATA WHICH IS A BILL GIGABYTES
OF DATA.
IF WE REALLY WANT TO MAP MOUSE
BRAIN NEUROSCIENCE HAS TO
EMBRACE BIG SCIENCE.
>> THERE HAVE BEEN IN THE
HISTORY OF SCIENCE MANY VERY
LARGE PROJECTS GOING TO THE MOON
IS A GOOD EXAMPLE OF AN INSANELY
LARGE PROJECT.
>> ENGINE STOP.
WE COPY EAGLE.
>> WHEN IT WAS PROPOSED, I THINK
PEOPLE THOUGHT THIS WAS PERHAPS
TOO CHALLENGING.
THE HUMAN GENOME WAS ANOTHER
PROJECT CONSIDERED
EXTRAORDINARILY HARD AND SOME
DOUBTED IT COULD EVEN BE DONE.
BUT THE HUMAN GENOME PROJECT WAS
COMPLETED SUCCESSFULLY AND LED
TO KEY BREAKTHROUGHS IN
MEDICINE, ANTHROPOLOGY, AND
FORENSIC SCIENCE.
SO WE TRIED TO DO THE SAME THING
HERE WITH DOING THE CONNECTOME.
IT ISN'T THE KNOWLEDGE ITSELF IT
IS AN INFRASTRUCTURE IT IS A
FOUNDATION, IT IS AN ENABLING
TOOL.
>> YOU CAN'T IMAGINE TRYING TO
UNDERSTAND THE BRAIN WITHOUT
THIS.
>> WHEN I STARTED IN THIS FIELD
50 YEARS AGO THERE WAS NO HOPE
OF DOING THIS.
IT WAS JUST VERY BEGINNING TO
GET STARTED WITH MANUALLY
TRACING THE C ELEGANS.
IF YOU LOOK AT THE FLY BRAIN,
EVEN A QUARTER OF THAT HAS
REVOLUTIONIZED THE THINKING
ABOUT CIRCUIT ANALYSIS IN THE
FLY BRAIN.
SO THE SAME THING WILL HAPPEN IN
THE MAMMALIAN BRAIN, IN THE
HUMAN BRAIN, THE MORE WE KNOW
THE BETTER WE CAN UNDERSTAND
WHAT'S GONE WRONG IN DISEASE
PROCESSES WHAT'S GONE RIGHT IN
GENIUS, I THINK ALL WE NEED TO
DO IN MOUSE BRAIN IS THE WILL TO
DO IT.
WE HAVE THE TECHNOLOGY, WE HAVE
THE PEOPLE WHO HAVE THIS
KNOWLEDGE.
IT IS A HUGE UNDERTAKING AND I
THINK WE JUST HAVE TO DECIDE AS
A COMMUNITY AND THAT IT IS WORTH
IT.
THIS IS THE INFORMATION WE NEED
IN ORDER TO ADVANCE THE FRONTIER
OF BRAIN SCIENCE.
♪
>> HELLO, EVERYONE, I WANT TO
THANK YOU FOR JOINING US TODAY.
THE STARS OF OUR FILM ARE HERE
AS WELL AS THE FILM MAKER AND
I'M SURE THERE ARE GOING TO BE
QUESTIONS FROM THE AUDIENCE BUT
THE QUESTION ON TOP OF MY MIND
RIGHT NOW IS, WHERE ARE WE ON
THAT MOUSE CONNECTOME AND WHERE
ARE WE ON THAT FLY CONNECTOME?
LET'S START WITH THE FLY.
THOSE OF YOU WHO WORK AT
GENELIA, WHERE ARE WE ON THE FLY
CONNECTOME?
>> I WILL START AND GWYNETH MAY
HAVE SOME COMMENTS.
I THINK WE ARE DONE WITH IMAGING
A COMPLETE FLY CONNECTOME AND
THAT MEANS WHOLE BRAIN WITH
VENTRAL NERVE CORD ATTACHED THAT
IS THE POT WITH HIGHEST RISK AND
IF THE IMAGE AND MOST OF IT IS
SEGMENTED BY GOOGLE, NOW
PROOFREADING IT.
SO I THINK WE ARE ABOUT A YEAR
AWAY OF REALLY HAVING THE
EQUIVALENT OF WHAT C ELEGANS HAS
COMPLETE CONNECTOME OF THE
ANIMAL AND OTHER PIECES, WORKING
ON VENTRAL NERVE, YOU HAVE HALF
THE BRAIN, OTHER CONNECTOME WORK
DONE ON THIS FLY, THIS IS MY FLY
WIRE SEGMENTATION ON THAT.
SO WE ARE GETTING THERE, AT
LEAST N OF 1 IN EACH GENDER.
>> THAT IS EXCITING.
AND WHAT IS HAPPENING WITH THE
EFFORT TO PRODUCE A MOUSE
CONNECTOME?
IS THERE ENERGY GATHERING AROUND
THAT?
>> MAYBE I CAN START BY SAYING I
THINK SO.
THE NIH RAN A BUNCH OF WORKSHOPS
TO SERIOUSLY CONSIDER WHETHER
THIS WOULD BE WORTH THE TROUBLE
AND EXPENSE.
THOSE WORKSHOPS I THINK
GENERALLY GAVE THE IMPRESSION
THAT IT WOULD BE WORTH DOING AND
PEOPLE HAVE LOTS OF SUGGESTIONS
ABOUT HOW TO DO IT AND NIH IS
JUST RECENTLY ANNOUNCED THE
FIRST GRANTS YOU CAN APPLY FOR
THE FIRST GRANTS TO THINK ABOUT
DOING A WHOLE MOUSE CONNECTOME,
IT IS NOT DOING A WHOLE MOUSE
CONNECTOME BUT SHOWING PROOF OF
CONCEPT TO DO A WHOLE MOUSE
CONNECTOME AND NUMBER OF US HERE
AND NUMBER OF PEOPLE GENERALLY
ARE TRYING TO FIGURE OUT WHAT
THEY MIGHT DO FOR THAT
PARTICULAR GRANT.
SO I THINK THAT IS GOING TO
HAPPEN, THAT WOULD BE A FIVE
YEAR GRANT STARTING SOMETIME
NEXT YEAR AND AT THE END OF
THOSE FIVE YEARS THE GOVERNMENT
IF ANYBODY IS SUCCESSFUL MIGHT
SAY YEAH, I THINK WE SHOULD NOW
THAT WE HAVE PROOF OF CONCEPT
LET'S DO THE WHOLE MOUSE.
HOW THAT WOULD GO I COULDN'T
POSSIBLY TELL YOU BUT THAT IS --
YEAH, IT IS QUITE EXCITING.
>> YOU ARE SAYING IN FIVE YEARS
WE WILL HAVE DRAWN UP A GAME
PLAN TO DO THE MOUSE CONNECTOME
AND THEN IT WILL BE ANOTHER FIVE
OR TEN YEARS BEYOND THAT.
>> I THINK -- I THINK THEY ARE
THINKING FIVE YEARS BEYOND THAT.
HOW COULD BE DONE IN FIVE YEARS.
IN THIS FIRST FIVE YEARS PEOPLE
WILL BE DOING VOLUMES THAT ARE
NOT A WHOLE MOUSE BRAIN BUT OUR
APPROACHES COULD BE IMAGINED TO
BE THAT OF MOUNTED DATA, LIKE
INSTEAD OF AN EXA BYTE MAYBE 20
PEDABYTES OF DATA, 10 CUBIC
MILLIMETERS.
>> DARREN HAVE WE HAD
BREAKTHROUGHS IN STORAGE AND
PROCESSING THE DATA?
>> YEAH, WELL I MEAN OF COURSE
COMPUTATIONAL TOOLS ARE GETTING
BETTER ALL THE TIME,
SPECIFICALLY FOR CONNECTOMICS I
WOULD SAY THERE OOH'S A COUPLE
OF DEVELOPMENTS, WE WORK WITH
JEFF'S TEAM TO FIGURE OUT A WAY
TO COMPRESS THE DATA, ALMOST 70
FOLD, COMPARED TO RAW FORM.
AND THAT REALLY I THINK THAT
REALLY WILL BE HELPFUL FOR A
HUGE PROJECT LIKE THE WHOLE
MOUSE BRAIN.
THEN WE WITH HAVE ALSO BEEN
WORKING ON METHODS TO FIGURE
WHAT IS THE CELL TYPE OF A SMALL
FRAGMENT OF WHAT IS AXON OR
DENDRITE AND TO DO THAT IN A WAY
THAT IS REALLY DRIVEN BY
COMPUTATIONAL INFERENCE RATHER
THAN HUMAN JUDGMENT.
SO THAT IS ANOTHER AREA ADVANCE
COMPUTER SCIENCE ADDING WHAT CAN
BE DONE IN NEURAL ANATOMY.
>> YES.
WHAT ABOUT -- WE HAVE A QUESTION
FROM THE AUDIENCE NOW.
IS THIS WORK BEING DONE ON JUST
ONE INDIVIDUAL OR AVERAGE ACROSS
MULTIPLE INDIVIDUALS?
I ASSUME THAT IS FOR BOTH THE
FLY AND THE MOUSE AND THE
ZEBRAFISH.
>> I THINK ONE OF THE CHALLENGES
OF CONNECTOMICS UNLIKE GENOME
SEQUENCING IS YOU HAVE TO DO IT
FROM ONE ANIMAL.
SO THAT MAKES IT CHALLENGING.
YOU NEEDED METHODS WHICH ARE
EXTREMELY RELIABLE COMPARED TO
STANDARD METHODS BIOLOGISTS.
I THINK THAT IS THE BEING
CHALLENGE DEVELOPING THE METHODS
IS RELIABILITY WE NEED TO DO A
BIG VOLUME.
>> RIGHT.
SO THERE WILL BE AN EVE OF THE
FLY, THE FLY CONNECTOME WILL
MAKE A STATUTE TO HER PERHAPS.
WHAT ABOUT JEFF, YOU SINCE THIS
FILM WAS MADE YOU HAVE PUBLISHED
A TINY PORTION OF THE HUMAN
CONNECTOME.
HOW IS THAT GOING?
>> SO THIS RAISES THE QUESTION
ABOUT ONE OFFS DOING SIMPLE
ANIMALS.
THIS IS ESPECIALLY PROBLEMATIC
IN MAMMALS WHERE THERE ARE
IDENTIFIED CELL TYPES BUT NOT
IDENTIFIED NEURONS AS SINGLE
ENTITIES WHICH IS THE CASE IN
MANY OTHER SPECIES OF ANIMALS
THAT ARE ESPECIALLY
NON-VERTEBRATE ANIMALS, AT LEAST
THERE ARE SOME CELLS
IDENTIFIABLE OR PAIRS OF THOSE
CELLS.
SO IF YOU DO WANT AN ANIMAL A
GENERAL CRITICISM IS WELL, THAT
IS ONE ANIMAL BUT WHAT IS THE
VARIATION, HOW DOES IT COMPARE
FROM ONE ANIMAL TO THE OTHER?
HOW DO YOU COMPARE BRAINS THAT
ARE WIRED A LITTLE DIFFERENTLY
PERHAPS BASED ON EXPERIENCE?
THIS IS A RESEARCH QUELL QUESTIN
ACTUALLY, WHAT IS THE
VARIABILITY BETWEEN ANIMALS OF
THE SAME SPECIES AND I THINK IN
FLY WE ARE GOING TO HAVE SOME
SENSE WE ALREADY HAVE SOME SENSE
IN C ELEGANS OF REMARKABLE
VARIABILITY EVEN IN ANIMALS THAT
ARE ISOGENIC.
40% OF THE CELL TO CELL
CONNECTIONS IN C ELEGANS ARE
DIFFERENT THAN THE EIGHT
CONNECTOMES WE DID OF C ELEGANS.
THEY ARE ALL THE SAME ISOGENIC
ANIMAL, IDENTICAL.
>> WITH ONLY 302 NEURONS,
AMAZING.
YES.
SO THERE IS A QUESTION OUT THERE
THAT SAYS COULD YOU GIVE US
GENERAL EXAMPLES OF BIG
OUTSTANDING QUESTIONS ABOUT
FUNCTION THAT WE ARE UNABLE TO
ANSWER NOW BECAUSE WE DON'T HAVE
THE FULL CONNECTOME?
>> I WOULD SAY HOW THE BRAIN
WORKS TO COMPUTE INFORMATION,
INTEGRATE SENSORY INTERNAL
INFORMATION THAT GUIDE BEHAVIOR.
THAT IS THE BIG QUESTION IN
NEUROSCIENCE, IT IS HOPELESS
WITHOUT THE CONNECTOME.
YOU CAN MAKE SLOW PROGRESS.
PEOPLE MAY PROGRESS IN HUMAN
GENETICS BEFORE CLONING AND
BEFORE MAPPING BUT THE PROBLEMS
ARE SO DIFFICULT, WE ARE TALKING
ABOUT THOUSAND, MILLION FOLD
EASIER.
I THINK THAT CAN BE SEEN OF A
FLY WHERE CONNECTOME IMMEDIATELY
MADE NEURAL BIOLOGISTS MORE
EFFECTIVE, WHICH NEURONS TOLD TO
STUDY, NOT PHYSIOLOGY OF
BEHAVIORAL EXPERIMENT BUT ABLE
TO PREDICT THINGS LIKE HOW
BRAINS DO VECTOR ALBUMIN BY
LOOKING AT THE CONNECTOME.
WHICH THEY HAD NO IDEA.
>> AND GWYNETH YOU ARE WORKING
DIRECTLY WITH FLY BEHAVIOR.
PERHAPS YOU CAN DESCRIBE IT IN
THE NITTY-GRITTY DETAIL.
>> I WANT TO GIVE AN EXAMPLE
UNDERSCORING WHAT JERRY SAID
FROM SOME OTHER BREAKTHROUGHS WE
HAD RECENTLY WITH CONNECTOMIC
DATA WE HAVE, A SUBSET OF THE
QUESTION JERRY OUTLINED IS A BIG
ONE IN NEUROSCIENCE, HOW DO YOU
CONVERT SENSORY INFORMATION TO
MOTOR INFORMATION.
YOU TAKE IN INFORMATION SENSES
BUT EVENTUALLY YOU HAVE TO
COMMAND YOUR BODY TO MOVE, IT
HAS BEEN A MYSTERY HOW YOU
CONVERT INFORMATION SENSORY
COORDINATES WHERE IT IS ON THE
RETINA, LOWER COORDINATES HOW DO
YOU MOVE A LIMB.
AND WITH THE HEMI BRAIN
CONNECTION WE HAVE, WE CAN SEE
IT WE CAN SEE NOW HOW SENSORY
NEURONS WE KNOW THEY ENCODE
BECAUSE OF THE PHYSIOLOGY AND
BEHAVIOR EXPERIENCE WE HAVE
DONE, LOOK UP SYNAPSE BY SYNAPSE
DESCENDING NEURONS AND WE KNOW
WHAT BEHAVIORS THOSE PARTICIPATE
IN SO WE CAN SEE THINGS NOW THAT
WERE INVISIBLE BEFORE LITERALLY
SENSORY MOTOR INTERFACE.
>> EXCELLENT.
ARE YOU DOING THE SAME THING
WITH THE ZEBRAFISH MARIELA?
>> YES, WE ACTUALLY HAVE --
ZEBRAFISH HAS THE SAME SIZE AS
THE FLIES, THE SAME REALM, IT
WAS A VERTEBRATE AS WELL SO WE
ARE INCHING TOWARDS THOSE
SOMEWHAT.
AND WHAT YOU GUYS MENTIONED IS A
STUDY OUTSTANDING QUESTION ON
ZEBRAFISH IS SENSORY TRANSFER.
AND HOW THIS GETS PROCESSED.
WE CAN ALSO TRACE INFORMATION
FROM THE SENSORY INPUT ALL THE
WAY TO THE MOTOR OUTPUT.
WHICH IS EXCITING WHICH IS AN
EXCITING PART OF WORKING MANY
THE CLINIC, SO YOU CAN SEE THE
CONNECTIONS AND FOLLOW THE
PATHWAYS.
WERE YOU GUYS SURPRISED WHEN YOU
SAW THE FINAL FILM AFTER HAVING
CONTRIBUTED SO MANY HOURS OF
YOUR OWN AND THANK YOU, VERY
MUCH FOR THAT.
ABOUT HOW IT CAME TOGETHER?
>> I WAS PLEASED.
HAVING TO LISTEN TO MYSELF TALK
WHICH IS ALWAYS ANOWING TO ME.
BUT I -- LARRY ONLY HAD ONE
MISTAKE I MADE ABOUT THE NUMBER
OF NEURONS, THAT MADE IT THROUGH
SO I MADE MANY OTHER MISTAKES SO
GOT RID OF -- I THINK HE DID A
GREAT JOB OF DOING IT TOGETHER
AND INTERESTING --
>> CURIOUS WHETHER YOU GUYS HAVE
SHOWN THIS FILM TO YOUR
STUDENTS, COLLEAGUES, FAMILY,
AND HAS IT BEEN HELPFUL TO YOU
TO LET PEOPLE WHO AREN'T IN THE
FIELD UNDERSTAND WHAT YOU ARE
DOING?
>> I HAVE SHOWN IT TO MY FAMILY
AND I THINK THEY FOUND IT
INCREDIBLY COMPELLING.
I KNOW IT'S TOLD SO ELOQUENTLY
AND I THINK AT A LEVEL THAT
EVERYONE CAN UNDERSTAND AND SO
IT REALLY HELPED THEM TO
APPRECIATE WHAT A CONNECTOME IS,
WHY WE WANT ONE, WHY SPENDING
ALL MY TIME, TRYING TO ACHIEVE
THIS.
YES.
>> GO AHEAD.
>> MY FAMILY LOVES EVERY PART OF
IT BUT THEY REALLY THOUGHT I
SHOULD HAVE HAD A SHAVE AND
HAIRCUT BEFOREHAND.
WAS THE YEN REACTION I GOT.
>> SURELY YOU DIDN'T LISTEN.
>> I SHOWED THE FILM TO MY
STUDENTS AND SAME WITH
CONNECTOMICS INTERNSHIP WITH
STUDENTS AND THEY FOUND IT
INSPIRING WHICH I THINK IS
ESSENTIALLY SCIENTISTS.
-- INSPIRING THE NEW SCIENTISTS.
>> THAT IS GREAT.
THERE IS A QUESTION ABOUT HOW DO
YOU DEFINE A CONNECTOME IN LIGHT
OF VARIABILITY OVER TIME WITHIN
A SINGLE BRAIN?
DON'T SOME PARTS OF THE BRAIN
INVOLVE CONSTANTLY TURNING OVER
CONNECTIONS?
AND THE EXAMPLE THIS PERSON GAVE
THIS IS TRYING TO DEFINE PROTEIN
STRUCTURE FOR INTRINSICALLY
DISORDERED PROTEINS.
>> THIS HARKENS BACK TO THIS
CHALLENGE OF THE N OF 1 WHERE
THAT IS KIND OF WHERE WE ARE
INTRINSIC STATE OF THE FIELD.
WE COMPARE LEFT AND RIGHT SAID
OF THE BRAIN WHEN WE HAVE A FULL
CONNECTOME, THAT GIVES SOME IDEA
OF VARIABILITY.
IN THE FLY WE ARE NOW GETTING TO
THE STATE WHERE WE HAVE MULTIPLE
DATA SETS AND WE HAVE ORIGINAL
DATA SET, WE HAVE A HEMI BRAIN
DATA SET, WE HAVE N OF 2 TO
COMPARE MAYBE NOT TO GIVE SENSE
WITHIN ONE BRAIN EXCHANGE OVER
TIME BUT BETWEEN INDIVIDUALS,
SIMILAR TYPE OF VARIABILITY,
STILL TRYING TO UNDERSTAND THAT.
THERE IS NOT THAT STRUCTURE
THERE, AT LEAST IN THE FLY BRAIN
THOUGH THINGS ARE FLEXIBLE AND
THEY DO CHANGE BUT THERE IS NOT
-- WE ARE STILL LEARNING A LOT
FROM THAT STRUCTURE.
>> I THINK WHO CONNECTED TO WHO
DOESN'T CHANGE AS MUCH AS THE
SIZE PLACES AN NUMBER OF
SYNAPSE.
AND I THINK WE WILL ABSOLUTELY
WITHIN FIVE YEARS HAVE 100 FLY
CONNECTOMES.
I WILL BE DOING THE MOUSE AND
HAVE A FREE WEEKEND AND HUNDRED
FLIES AND DIRECT THE DATA.
SO WE WILL HAVE -- WE WILL ADD
VALUE.
NOT SAYING WE DON'T WANT MORE
THAN ONE.
>> WE CAN LOOK AT THINGS LIKE
GENDER DIFFERENCES NURTURING
DIFFERENCES, SO FORTH.
>> EXACTLY.
>> THERE ARE VOTES AGAIN FOR
THIS QUESTION AS WITH THE GENOME
ARE THE COSTS FOR DOING A FLY
CONNECTOME DECREASING QUICKLY?
WILL THAT ENABLE LOOKING AT
MULTIPLE INDIVIDUALS TO MAP
VARIATIONS IN CONNECTIVITY OR
ACROSS SEX?
THIS FOLLOW WHAT YOU JUST SAID.
>> I THINK WE DECREASED BATCH OF
10,000 WHEN WE STARTED IN 2007.
I THINK THE MOUSE HAVE TO GO
DOWN ANOTHER FACTOR OF A
THOUSAND WHICH I THINK WILL
HAPPEN IF THE GRANTS ARE FUNDED
AND TECHNOLOGY DEVELOPED.
>> THAT IS FACTOR OF TEN TO THE
6, 10 TO THE 7, NOT 10 TO 14
SEQUENCING BECAME ACHIEVED FROM
FIRST SEQUENCES NOW.
YOU CAN GO ON FLIES MOUSE BRAIN.
>> WHAT ABOUT AT GOOGLE THOUGH?
ARE THINGS GETTING CHEAPER
THERE?
BY DOING THE SAMPLING?
>> CERTAINLY THE COST OF RUNNING
SAY LARGE NEURAL NETWORKS ON
LOTS OF DATA THAT IS GETTING
CHEAPER ALL THE TIME, PEOPLE ARE
WORKING HARD ON NEW KINDS OF
CHIPS THAT ARE SPECIALIZED FOR
THESE TYPES OF PURPOSES, NEW
ALGORITHMS THAT ARE MORE
EFFICIENT, MORE ACCURATE SO I
THINK WE BENEFIT FROM ALL THE
INVESTMENTS GOING ON IN THAT
SPACE.
OBVIOUSLY THE VAST MAJORITY OF
WHICH IS NOT DRIVEN BY ANYTHING
RELATED TO BIOLOGY CONNECTOMICS,
BUT NONETHELESS HAS SIMILAR
PLATFORMS AND SIMILAR
TECHNOLOGIES SO WE CAN BENEFIT.
>> I THINK IT IS WORTH HAVING
SHOUT OUT THE GOOGLE WHO DID ALL
OUR CONNECT ALL OUR COMPLICATED
SEGMENTATION AND DIDN'T TAKE ANY
MONEY FROM US TO DO THAT WAS A
GREAT PUBLIC SERVICE OF THAT
COMPANY.
SO REALLY ENABLE THE FIELD I
WOULD SAY.
>> THERE CONTINUES TO BE STRONG
SUPPORT FOR THAT AT GOOGLE?
>> YES.
IN FACT WE ARE EXCITED ABOUT THE
NEW NIH BRAIN CONNECTIONS WHICH
JEFF TALKED ABOUT THE GOAL WAS
ESTABLISH HOW TO SCALE A MOUSE
BRAIN AND WE HOPE TO
PARTICIPATES IN THAT PROGRAM.
WE ARE NOT PLANNING TO TAKE ANY
MONEY FROM THE GOVERNMENT BUT
JUST CONTRIBUTE OUR TIME AND
RESOURCES.
I THINK PHILOSOPHICALLY THERE IS
JUST A LOT OF INTEREST IN
ADVANCING SCIENCE.
AT GOOGLE AND WE ARE -- WE ARE
PLEASED TO PARTICIPATE IN THESE
PROJECTS.
>> OKAY.
THERE IS A QUESTION HERE ABOUT
OPPORTUNITIES FOR PUBLIC PRIVATE
PARTNERSHIPS, COMMERCIALIZATION.
GENOMICS CHANGED HOW BIOMEDICAL
RESEARCH IS DONE AND BENEFITS
FROM PUBLIC PRIVATE PARTNERSHIPS
FOR EXAMPLE LUMINA, DO YOU FOR
SEE SIMILAR PRIVATE INVESTMENTS
AS OFFSHOOTS FROM THE PUBLIC
INVESTMENT?
ANY OF YOU?
>> I THINK WE SHOULD ACKNOWLEDGE
THAT THERE'S ALREADY BEEN PART
OF PUBLIC COLLABORATION THROUGH
GOOGLE AND PRIVATE ENTITY.
SO ALREADY GOING ON.
MAYBE SOMEONE WITH MORE MAYBE
JEFF ANSWER, I THINK IT IS
LOGICAL THAT HES USED TO SAY A
LOT OF DISEASES AUTISM,
SCHIZOPHRENIA, ARE CONNECTOMIC
DISEASES.
IMAGINE PEOPLE DO A BIOPSY AND
CONNECTOME IN THAT TINY PART OF
THE BRAIN AND STAGES LOOK
FORMAL, WHAT DOES IT LOOK LIKE
PARTICULAR SYNDROME.
THAT COULD HAPPEN AS A
DIAGNOSTIC TOOL.
>> ALL RIGHT.
>> I'M SORRY TO INTERRUPT CAROL.
THE VERY BIG SCANNING MICROSCOPE
THAT IS USED IN MY LAB AND USED
AT GENELIA WAS BUILT BY --
WITHOUT REALLY A GOOD MARKET
PLAN THEY WERE GOING TO SELL
MILLION OF THESE AND IN FACT
THEY HAVEN'T.
THIS WHOLE LARGE NUMBER BUT THEY
ARE VERY, VERY TRANSFORMATIVE
FOR OUR FIELD.
THAT IS ANOTHER PARTNERSHIP THEY
WEREN'T FREE I MIGHT ADD BUT
CERTAINLY THEIR INVESTMENT WAS
MUCH GREATER THAN THEROFITS
THEY ARE REAPING AT LEAST FROM
THE BIOLOGISTS.
I THINK NOW THERE ARE SOFTWARE
COMPANIES STARTED UP SEBASTIAN
SIGN STARTED A COMPANY THAT IS
REALLY GOT IS VERY USEFUL FOR
HELPING PEOPLE DO THINGS
OTHERWISE WOULD HAVE TO BE DONE
BY INDUSTRIAL PARTNER LIKE --
GROUP.
>> I WANT TO ASK LARRY KLEIN A
QUESTION, LARRY, YOU MET ALL
THESE PEOPLE, WORKED WITH THEM
FIGURED HOW TO FILM REMOTELY.
WHAT DID YOU LEARN FROM THIS
EXPERIENCE ABOUT TELLING THIS
STORY?
>> I KNEW NOTHING ABOUT THE
SUBJECT, NOT AN OUNCE.
SO EVERYTHING WAS A BUILD FOR
ME.
NEEDING EVERYONE AND WATCHING
HOW THEY WORKED WAS JUST
STAGGERING ANDS THAT FASCINATING
AND I MEAN THAT SINCERELY, I
HAVE DONE A LOT OF SCIENCE
FIPPLES BUT THIS ONE KNOCKED --
FILMS BUT THIS KNOCKED MY SOCKS
OFF BECAUSE YOU ARE WORKING
SCALE, NOT ONLY SCALE AND
RESOLUTION LEVELS HAVE TO BE
ACHIEVED HERE, WAS NOTHING THAT
WAS AVAILABLE TO ANYONE.
I DON'T KNOW FIVE, SIX, SEVEN
YEARS AGO BUT SEEING THE
PROGRESS FROM HOW SIDNEY PRESENT
NEAR AND FOLKS DID C ELEGANS TO
WHAT IS HAPPENING NOW, THAT TO
ME REALLY IS TOLD THE STORY IN
WAYS THAT I COULDN'T HAVE
IMPROVED ON.
THE WAY EVERYBODY DESCRIBED WHAT
THEY DID, IT TOOK ME I DON'T
KNOW HOW LONG TO TRY TO FIGURE
OUT WHAT VIREN WAS TALKING
ABOUT.
I MEAN WAS DOING AND WE JUST
PATIENTLY WENT THROUGH IT, AND
I'M STILL CURIOUS, WHEN BOBBY
AND I WERE DOING WORK TOGETHER
WE WERE TRYING TO -- I WAS
TRYING TO FIGURE OUT WHERE ARGON
WAS -- WHERE THE NATIONAL LAB
COMPONENT ENTER IN THIS PROCESS
IS MY OWN QUESTION, NOT
ANSWERING YOUR QUESTION.
THAT IS ONE THING I DIDN'T FEEL
LIKE I HAD ENOUGH OF A HANDLE
ON.
TO TALK ABOUT MORE IN THE FILM.
I WOULDN'T MIND HEARING A FEW
BITS FROM BOBBY ABOUT THAT NOW
IF THAT IS OKAY WITH YOU.
>> SURE, BOBBY.
>> SO I THINK FIRST THANK YOU,
LARRY FOR THE COMPLIMENTS.
THE REASON IT IS NEBULOUS IN THE
DOCUMENTARY IN YOUR MIND IS A
STILT A LITTLE NEBULOUS IN MY
MIND.
BUT I WILL TELL YOU
HISTORICALLY, THE NATIONAL LABS
HAVE OFTEN HELPED A LARGE SCALE
IMAGING AND DATA PROJECTS
WHETHER THAT IS THE UNIVERSE AT
ONE SCALE OR CRYSTALLOGRAPHY AT
THE OTHER SCALE, SO THEY ARE
GOOD AT DOING THIS.
THEY ARE GOOD DOING SCIENCE AT
SCALE.
WHAT IS MYSTERIOUS TO ME AND
PERHAPS MYSTERIOUS TO OTHER
PEOPLE IS LABS ARE RUN BY
DIFFERENT FEDERAL AGENCY THAN
THE NIH FOR EXAMPLE THERE. IS A
LOT OF DISCUSSION AT SOME VERY
HIGH LEVEL AMONG AGENCIES THAT I
THINK IS THE PART THAT IS
INTERESTING AND WILL COME TO
FRUITION SOON.
TURNS OUT I GAVE YOU ANOTHER
NEBULOUS ANCILLARYRY, WHICH IS
-- WE USE TO -- BECAUSE I DON'T
HAVE MUCH MORE TO SAY.
WE USE THEM AND WE BENEFIT FROM
THE RESOURCES THEY HAVE
TREMENDOUSLY FOR THE WORK THAT
WE ARE DOING.
WHETHER AGENCIES CAN GET MARRIED
COMFORTABLY IS A SEPARATE
QUESTION ABOVE OUR PAY GRADE.
>> THE OTHER THING I WOULD SAY
IS I WAS VERY DISAPPOINTED,
BECAUSE OF THE PANDEMIC, I
WANTED TO GET INTO MARIELA'S
LABS AND SEE THOSE ZEBRAFISH AND
ALL THE THINGS THAT I COULDN'T
DO.
I MEAN WE RELIED ON FOOTAGE, IN
FACT THE BITS ON THE ZEBRAFISH
MARIELA SHOT FOR US IN THE LAB
BECAUSE I COULDN'T GET IN THERE.
>> SHE DREW PICTURES OF
COLLABORATORS.
>> GOSH THEY WERE GREAT M. EVEN
JEFF'S LAB AT HARVARD WHERE WE
ALL STARTED, WE HAD TO USE WHAT
THEY ALREADY HAD AND WHAT JEFF
HAD ALREADY HAD.
SO GENELIA HAVE A LOT OF FOOTAGE
WE WERE ABLE TO USE SOME OF
WHICH IS PROBABLY MORE DATED
THAN JERRY AND GWYNETH WOULD
HAVE LIKED BUT THAT'S ALL WE
HAD, WE COULDN'T GET IN, IT WAS
FRUSTRATING NOT TO GET IN THERE
AND DO THIS STUFF BUT DID THE
BEST WE COULD.
>> WELL, YES, I THINK YOU DID A
VERY GOOD JOB.
>> OKAY SO WHAT IS THE STORY
NEXT TO BE TOLD?
WHAT OTHER ACTIVITIES ARE YOU
GUYS INVOLVED IN TO KEEP THE
PUBLIC AWARE OF YOUR WORK AND
THE IMPORTANCE OF YOUR WORK?
>> I THINK WITH FLY PEOPLE WOULD
LIKE TO SEE IF WE CAN ACHIEVE
THE PROMISE OF UNDERSTANDING HOW
THE FLY BRAIN CAN DO ALL THE
WONDERFUL THINGS THE FRUIT FLY
DOES, HOW WE USE THE CONNECTOME
TO GLEAN INFORMATION AS -- TO
ANSWER THE QUESTION AS WHY YOU
WANT TO DO CONNECTOMES IN ANY
CASE.
>> YES.
>> I'M HOPING MAYBE THIS FILM
CAN HELP THOSE OF YOU WHO ARE
GOING FOR THE MOUSE PRIZE TO
MOTIVATE OTHERS TO GO FOR IT.
>> IS ALLEN INSTITUTE STILL
INVOLVE -- THEY ARE STILL
INVOLVED, RIGHT?
>> I THINK SO.
>> YES.
OKAY.
AND GWYNETH, ARE YOU STILL
CONCENTRATING ON THE SAME WORK
WITH THE FLY JUMPING?
>> WE CONTINUE THAT WORK BUT
CONNECTOME HAS INSPIRED US, NOW
WE CAN BASICALLY MOVE TO
NEIGHBORING CIRCUITS,
NEIGHBORING ZEBRAFISH -- COVER
ALL VISUAL BEHAVIORS WE CAN AND
KIND OF INCORPORATE THEM TO SOME
KIND OF UNDERSTANDING.
IT IS AMAZING THE SCOPE WE CAN
TRY TO UNDERTAKE NOW.
>> AND ARE YOU -- WHAT JOURNALS
ARE YOU MOSTLY PUBLISHING THIS
CONNECTOME THAT IS RELATED
RESEARCH?
>> WELL, WE TRY TO SPREAD AROUND
IF WE CAN BUT I WILL SAY ELI HAS
BEEN VERY FRIENDLY TO THIS
RESEARCH.
LARGELY BECAUSE THERE'S NO LIMIT
IN TERMS OF NUMBER OF FIGURES
YOU CAN PUT OUT AND THERE'S JUST
SO MUCH DATA THAT WE WANTED
SHARE OUT THERE FOR EVERYONE TO
BE ABLE TO WADE THROUGH BECAUSE
THAT IS A GOOD AVENUE FOR US.
>> LOOKS LIKE OUR TIME IS UP.
THANK YOU FOR SHARING THAT
GWYNETH.
THANK YOU ALL OF YOU,
JEFF,BOBBY, JERRY, MARIELA LARRY
AND VIREN.
THANK YOU FOR JOINING US FOR
THIS SESSION.
THANK YOU FOR HELPING US MAKE
THIS FILM.
GOOD LUCK WITH THE RESEARCH.
>>HELLO EVERYONE, WELCOME TO
TODAY'S SYMPOSIUM ON BEHAVIORAL
QUANTIFICATION FROM TRACKING TO
UNDERSTANDING.
SO WHAT THE NIH BRAIN INITIATIVE
IS FOCUSED ON RECENTLY IS
DEVELOPING A SUITE OF
TECHNOLOGIES FOR ILLUMINATING
THE FOUNDATION OF BEHAVIOR.
THOSE TECHNOLOGIES MAINLY FOCUS
ON THINGS LIKE CONNECTOMICS
REVEAL WIRING PATTERNS OF THE
BRAIN, MANIPULATING MEASURING
GENES AND ALSO MANIPULATING
MEASURING ACTIVITY BUT LITTLE
UNTIL RECENTLY FOCUS ON
QUANTIFYING THE RICHNESS OF
BEHAVIOR ACROSS CONTINUE TEXT
AND THAT'S THE FOCUS OF TODAY'S
SIMILAR POSE UP, REVIEW RECENT
AT VANCES IN THIS REALM,
TECHNOLOGY FOR BEHAVIORAL
QUANTIFICATION AND HOW WE CAN
MOVE TOWARDS BETTER
UNDERSTANDING OF THE BRAIN BY
DEVELOPING THESE TECHNOLOGIES AN
LINKING UP TO OTHER
TECHNOLOGICAL FOCUSES OF THE
BRAIN INITIATIVE.
SO REALLY FOR THE FORE OF WHAT
WE WANT TO DISCUSS AND THE
REASON WE NEED BEHAVIORAL
TECHNOLOGIES WE NEED TOOLS AND
THEORY TO LINK ENVIRONMENT AND
HIGH DIMENSIONAL MEASUREMENT OF
BRAIN ACTIVITY WITH HIGH
DIMENSIONAL MEASUREMENT OF BRAIN
OUTPUT, THUS FAR MEASUREMENT OF
BEHAVIOR HAS BEEN LOW
DIMENSIONAL OR CONSTRAIN AND
THIS IS SOMETHING TO CHANGE.
WE ALSO BY CREATING NEW
TECHNOLOGIES FOR BEHAVIORAL
MEASUREMENT WE BETTER PROBE THE
CAUSAL RELATIONSHIPS BETWEEN
BRAIN CONNECTIVITY AND BEHAVIOR,
WITH BETTER BEHAVIORAL
MEASUREMENT TECHNOLOGIES WE ABLE
TO HAVE NEW SENSITIVE FOR
ASSESSING BRAIN DISORDERS AND
ASSESSING THE EFFECT OF VARIOUS
THERAPIES.
SO RECENTLY AS I'M SURE MOST OF
YOU ARE AWARE THERE'S EXPLOSION
IN DIFFERENT TECHNOLOGIES
MEASURING BEHAVIOR AND ASPECT OF
BEHAVIOR AND SEE THAT THE THE
SCHEMATIC HERE ON THE TOP
DEVELOPED BY TOM FERERRA SO A
RENAISSANCE IN TECHNOLOGY
BEHAVIOR, WHAT WE WANT TO DO
TODAY IS DISCUSS A FEW EXAMPLES
OF THIS TECHNOLOGIES AND THEN
THINK WHERE WE GO FROM HERE.
TOUCH OF QUESTIONS WE WILL
DISCUSS TODAY IN THE PANEL AFTER
SET OF TALKS HOW CURRENT TOOLS
ECOSYSTEM COMPLIMENT EACH OTHER
AND WHAT TECHNOLOGY ARE WE STILL
MISSING.
HOW WE GET TOOLS IN HANDS OF
EWERS AND MAKE THEM EFFECTIVE.
DEVELOP RELATIONSHIPS BETWEEN
TOOL BUILDERS AND PRACTITIONERS
AND HOW CAN WE ANALYZE HIGH
RESOLUTION BEHAVIORAL DATA SETS
LINK TO BRAIN MEASUREMENTS AND
MOVE FROM TRACKING TO
UNDERSTANDING.
THAT WILL INVOLVE PRIORITIZING
DIFFERENT TYPES OF MODELING
THEORY WE WILL ALSO DISCUSS
TODAY.
SO THE FORMAT OF SYMPOSIUM TODAY
WILL BE A SET OF SHORT LIGHTNING
TALKS FIVE MINUTES EACH FIRST BY
THREE SPEAKERS THAT ARE
DEVELOPING TOOLS, SO JAN
ZIMMERMANN UNIVERSITY OF
MINNESOTA DEVELOPING SPECIALIZED
HARDWARE FOR BEHAVIORAL
QUANTIFICATION, THEN GIVE A
BRIEF TALK ON WORK TO DEVELOP
SOFTWARE OR BEHAVIORAL
QUANTIFICATION AND ALSO VERY
LARGE DATA SETS FOR TRAINING AND
BENCHMARKING, BEHAVIORAL
QUANTIFICATION TECHNOLOGIES AND
JENNIFER SUN FROM CAL TECH WILL
TALK ABOUT HER WORK TO GO FROM
BEHAVIORAL QUANTIFICATION TO
CLASSIFICATION OF ACTIONS, AND
MORE GENERALLY BEHAVIORAL
QUANTIFYCATION IN DIFFERENT
CONTEXT INCLUDING SOCIAL
BEHAVIOR.
AFTER THOSE LEE TALKS ON TOOL
BUILDING WE WILL HAVE TALKS ON
APPLICATIONS, FROM THE
PRACTITIONERS, AND FIRST TALK
WILL BE CHRIS NIELL UNIVERSITY
OF OREGON, IT WILL BE ON
APPLYING BEHAVIORAL
QUANTIFICATION TO STUDY OF
ETHOLOGY AND LINKING BRAIN
ACTIVITY TO BEHAVIOR.
THEN BING BRUNTON, UNIVERSITY OF
WASHINGTON WILL TALK ABOUT HER
WORK ON MODELING AND THEORIES AS
RELATES TO BEHAVIORAL
QUANTIFICATION WITH EMPHASIS ON
AGENT BASED MODELS.
FINALLY TIM GENTNER FROM UCSD
GIVE A SHORT TALK ON HIS WORK TO
UNDERSTAND THE NEURAL BASIS OF
VOLCAL COMMUNICATION.
ONCE THOSE TALKS ARE DONE WE
WILL THEN HAVE A 40 MINUTE PANEL
DISCUSSION, FIRST MODERATED
QUESTIONS, THAT WE THINK ARE
VERY IMPORTANT, OR DISCUSSING
WITH Y'ALL AND THEN WE WILL OPEN
UP TO Q&A FROM THE AUDIENCE.
WITHOUT FURTHER ADIEU.
>> HEY EVERYONE.
STILL WAITING FOR MY SLIDES TO
ACTUALLY COME UP.
I DON'T SEEK TO SEE MY FIRST
INTRO SLIDE.
DOESN'T MATTER.
I'M JAN ZIMMERMANN MY LAB
FOCUSED ON DEVELOPING TOOLS FOR
TRACKING NON-HUMAN PRIMATES, I I
WANT TO TALK ABOUT BRIEFLY WHY
TRACKING NON-HUMAN PRIMATES IS
SO HARD.
FIRST YOU NEED LARGE CAMERA
SYSTEMS THAT ARE BASICALLY
REQUIRED TO ACHIEVE HIGH
PRECISION ESTIMATION OF ANIMALS
SUCH AS NON-HUMAN PRIMATES.
THESE ANIMALS ARE ACROBATS AND
COVERED IN MONOTONE FUR AND
BASICALLY GO INTO LOTS OF
DEGREES OF FREEDOM AND JUMP
AROUND THE ROOM.
WE NEED TO BE ABLE TO ACHIEVE
CALIBRATION OF INTRINSIC AN
EXTRINSIC OF ALL THE CAMERAS IN
THESE SYSTEMS AND THIS IS
NON-TRIVIAL IF YOU HAVE A LARGE
CAMERA SYSTEM BECAUSE THEY CAN
BE SHIFTED AROUND AND IT HAS TO
BE RELIABLE ON A DAILY BASIS.
IF THE DATA RATES THESE SYSTEMS
PRODUCE SUCH AS OUR MONKEY
STUDIO 1.0 SYSTEM OUR EXTREMELY
SWORNTANT SO OUR SYSTEM PRODUCES
7.4 TERABYTES AN HOUR.
EXORBITANT.
THERE WERE NO STATE OF THE ART
DATA SETS AVAILABLE SO WE HAVE
DONE IN A 2020 COMMUNICATIONS
PAPER IS BASICALLY DEVELOPED THE
FIRST HARDWARE AND SOFTWARE
INTEGRATED SOLUTION THAT ALLOWS
US TO ACHIEVE BOTH RECONSTRUCTS
IN NON-HUMAN PRIMATES TRAVERSING
A LARGE ENCLOSURE AS YOU CAN SEE
ON THIS SLIDE.
NOW, ONE OF THE THINGS WE
LEVERAGE TO MAKE OUR JOBS A TINY
BIT EASIER IS USING MULTI-VIEW.
AND BY USING MULTI-VIEW AS YOU
CAN SEE ON THE TOP PANEL WE CAN
SEE FOR EXAMPLE ONLY CLASSIFIED
BOTH POINTS IN COUPLE OF IMAGES
AND THEN WE PROJECT THOSE
RECONSTRUCTIONS THROUGH ALL
OTHER CAMERA SYSTEMS THAT HAVE
BEEN PREVIOUSLY CALIBRATED.
THUS BASICALLY AUGMENTING AND
BOOSTING OUR TRAINING SETS
DRAMATICALLY WHILE KEEPING
COSTSES DOWN A LITTLE BIT.
ON THE LOWER PANEL I'M SHOWING
YOU PERCENTAGE OF RECONSTRUCTION
FOR DIFFERENT JOINTS IN OUR DATA
SETS, AS A FUNCTION OF THE
NUMBER OF CAMERAS OR INFERENCE.
I HOPE YOU CAN APPRECIATE USING
LOCAL RA SYSTEMS SUCH AS TWO,
FOUR, EIGHT, TEN CAMERAS DOESN'T
ACHIEVE A VERY GOOD JOB.
AND ONLY AS YOU START INCREASING
THE CAMERA COUNTS TOWARDS 48 OR
62 IN OUR CASE YOU CAN GET
REALLY GOOD ACCURATE
RECONSTRUCTION.
NOW THE LAST PART THAT IS
INCREDIBLY IMPORTANT OF COURSE
WHEN YOU ARE TRYING TO RECORD
NEURAL DATA WHILE DOING
BEHAVIORAL CLASSIFICATION IN
THESE TYPES OFS IS WORKING ON
THE RECORDING APPROACHES IN
FREELY MOVING NON-HUMAN PRIMATE.
ON THE LEFT YOU CAN SEE THE
FIRST APPROACH AND NETWORK SCALE
IMPLANT WITH WIRELESS DATA
LOGGER IMPLANTED IN ANIMAL THAT
ALLOWS US TO RECORD FROM 128
CHANNELS BASICALLY IN PUSHING
INSIDE THE PREFRONTAL CORTEX,
VERY RELIABLE.
HOWEVER, IN THE FUTURE WE NEED
MULTI-SITE RECORDING TECHNOLOGY,
IT HAS TO BE WIRELESS, AND HAS
TO BE BUILT TO LAST AND SO ONE
OF THE THINGS THAT WE HAVE
STARTED COLLABORATING WITH
OTHERS SUCH AS (INDISCERNIBLE)
FROM SPIKE GADGETS IS
INTEGRATING FLEXIBLE ELECTRONICS
THAT ARE HELD ON LITTLE NEEDLES
THEN EXTRACTED FROM THE PAIN AND
BASICALLY CIRCUMVENT THE
PULLIZATION OF TISSUE.
WITH THAT, I'M GOING TO GIVE TO
NEXT PERSON.
>> HI EVERYONE I'M DON, SENT --
TIM DUNN, VICE PRESIDENT OF
DEVELOPMENTAL ENGINEERING AT
DUKE.
MY FOCUS IS DOING SOFTWARE FOR
THREE DIMENSIONAL HOST E
ESTIMATION AND LABORATORY ANIMAL
PRIMARILY RODENTS.
WE HAVE DEVELOPED A METHOD
CALLED DANCE WHICH STANDS FOR
THREE DIMENSIONAL ALYING NETWORK
FOR COMPUTATIONAL SOLID WHICH
USES METRIC RECONSTRUCTION TO
PREDICT THREE DIMENSIONAL
POSITIONS OF JOINTS ON ANIMALS
BODY AND TRACK THOSE OVER TIME.
THIS WORK IS DONE IN
COLLABORATION WITH
(INDISCERNIBLE) AND HIS LAB AT
HARVARD UNIVERSITY.
SO TO TRAIN THIS ALGORITHM ONE
HINGE WE DID FIRST WAS TO TAKE A
QUEUE FROM THE 3-D HUMAN POSE
ESTIMATION FUEL WHICH PEOPLE
DEVELOPED LARGE DATA SETS FOR
TRAINING AN BENCHMARKING THEIR
ALGORITHMS.
WE LACK THIS TYPE OF DATA SET
AND LABORATORY RODENTS JAN
MENTIONED ABOUT DEVELOPING LARGE
DATA SETS IN NON-HUMAN PRIMATES
BUT FOR RODENTS WE LACKED THESE
TYPES OF DATA SO TOGETHER WITH
JESSIE MARSHALL AND VINCE'S LAB,
WE DEVELOPED A DATA SET CALLED
RAT 7M, 7 MILLION FRAMES OF
COLOR VIDEO FRAMES FROM SIX
DIFFERENT VIEWS.
PAIRED TOGETHER WITH THREE
DIMENSIONAL MOTION CAPTURE DATA.
THE IDEA IS YOU TICK A RAT AND
THEN YOU CAN PUT LITTLE MARKERS
ON THE BODY.
THOSE MARKERS CAN BE TRACKED
USING A MOTION CATCHER SYSTEM ON
DIFFERENT CAMERAS TO RECONSTRUCT
THREE DIMENSIONAL POSITION OF
THOSE MARKERS AND AT THE SAME
TIME YOU CAN BE COLLECTING
SYNCHRONIZED COLOR VIDEO DATA
FROM SIX CAMERAS CALIBRATED INTO
THE SAME ORDINANCE SYSTEM AS
MOTION CAPTURE SO YOU HAVE THIS
VIDEO DATA SEASON CROW
RECOGNIZED WITH HIGH RESOLUTION
3-D DATA AND BUILD ALGORITHMS
FROM THE COLOR VIDEO DATA
INSTEAD OF LARGE MOTION CAPTURE
ARRAY TO GET THE SAME 3-D OUT
INSTEAD OF MEASURING BEHAVIOR IN
THESE ANIMALS.
SO WE TOOK RATS 7M AND CLUSTER
IT INTO A BUNCH AFTER
CATEGORIES, THAT IS USEFUL FOR
DATA DURING TRAINING AND ALSO
FOR DEVELOPING BENCHMARKS THAT
ARE SPECIFIC TO INDIVIDUAL TYPES
OF BEHAVIORS AT THE BOTTOM.
WE ALSO COLLECTED A DIFFERENT
DATA SET WHICH WAS TWO
INTERACTING RATS, CALLED PAIR R
24M, THAT STANDS FOR 24 MILLION
FRAMES OF COLOR VIDEO AND WHEN
USED VERY SIMILAR TECHNIQUE WE
ALSO PUT MARKERS ON THESE
ANIMALS UNFORTUNATELY COULDN'T
TRACK THE LIMBS AS WELL IN THESE
SOCIAL INTERACTING ANIMALS
BECAUSE OF THESE OCCLUSIONS WHEN
THEY ARE MOSTLY INTERACTING SO
WE HAVE FEWER POINTS ON THE BODY
BUT STILL HAVE VERY RUTH
BEHAVIORAL DATA SETS WE
COLLECTED OVER MANY DIFFERENT
INTERACTING RAT PAIRS.
WHAT YOU SEE IN THIS VIDEO DOWN
BELOW IS AN ILLUSTRATION OF SOME
OF THE DATA PAIR R 24M AND THERE
IS A LITTLE BEHAVIORAL MAPPING
RECOMMENDATION, THAT IS TELLING
US OF THESE INSAN TRAINIOUS
BEHAVIORS THESE ANIMALS ARE
ENGAGED IN, YOU CAN SEE THAT
ANIMATING OVER TIME.
ON THE RIGHT YOU SEE RAW
EXAMPLES OF THIS PAIR R 24M DATA
SET WHERE WE TAKE THREE
DIMENSIONAL POSITION OF LAND
MARKS AND PROJECTED DOWN ON TO
THE INDIVIDUAL VIDEO FRAMES.
SO VERY RICH MULTI-ANIMAL 3
DIMENSIONAL BEHAVIORAL DATA SET.
SO ONE THING WE HAVE DONE IS
DEVELOP SOME SOFTWARE THAT
RELIES ON BIG DATA SETS WE
COLLECTED, THIS IS THE DANCE.
THE DANCE TECHNOLOGY I MENTIONED
AT THE BEGINNING.
SO YOU CAN SEE OUTLINE OF WHAT
THAT TECHNOLOGY LOOKS HERE.
WE TYPICALLY USE SIX CAMERAS
THAT ARE SYNCHRONIZED THROUGH
THIS VOLUME METRIC
REPRESENTATION THESE INDIVIDUAL
IMAGES AND USE THREE DIMENSIONAL
CONVOLUTIONAL NETWORK TOE RATHER
THAN THIS BIG FOLD CAMERA MOTION
CAPTURE SYSTEM.
IN DOING SO YOU CAN GET THIS
FULL 3-D BODY TRACKING EVEN IN
ANIMALS THAT AREN'T BARING
MARKERS.
WE WORK A LOT IN RATS AND YOU
CAN SEE PREDICTION OF THOSE OF
DANCE ON COUPLE OF INTERACTING
RATS HERE.
ON THE BOTTOM YOU CAN SEE
EXAMPLES HOW WE CAN EXTEND
TRACKING TO DIFFERENT SPECIES
INCLUDING MICE AND DRAMATICALLY
DIFFERENT BODY PLANS FOR
INSTANCE IN BIRDS, SO IT IS THE
FLEXIBLE TOOL THAT WE ARE TRYING
TO CREATE AND PROVIDE COMMUNITY
TO MAKE THESE HIGH RESOLUTION
BEHAVIORAL MEASUREMENTS.
NEXT IS JENNIFER SUN.
>> HI, EVERYONE.
I'M JENNIFER.
I'M CURRENTLY A Ph.D. STUDENT
AT CAL TECH AND BROADLY SPEAKING
REALLY INTERESTED IN DEVELOPING
METHODS THAT CAN HELP SCIENTISTS
ANALYZE LARGE AMOUNTS OF
RECORDER SITES BIG DATA.
FOR EXAMPLE FOR AUTOMATICALLY
QUANTIFYING BEHAVIOR FROM VIDEOS
SO MORE SPECIFICALLY SEEK -- WE
ARE SPECIFICALLY SEEKING ON THE
PAST I WORKED ON MACHINE
LEARNING METHODS THAT INTEGRATE
LEARNING FROM BOTH HUMAN DOMAIN
EXPERTISE AS WELL AS DATA.
I ALSO WORKED ON METHODS THAT
CAN DISCOVER STRUCTURE FROM REAL
BROAD DATA IN ABSENCE OF HUMAN
INPUT.
I'M ALSO INTERESTED IN SYMBOLIC
MODELING WHICH HAS POTENTIAL TO
HELP DEVELOP INTERPRETABLE
BEHAVIORAL MODELS.
FURTHER RESOLUTION OF THIS SHORT
TALK I WILL FOCUS ON THE METHODS
THAT CONTACT BEHAVIOR FROM POST
DATA SO INTRODUCE EARLIER IN
THIS SESSION WE CAN DO KEY POINT
ESTIMATION ON TOP OF VIDEO DATA,
OUR GOAL IS TO GO FROM THESE KEY
POINTS THEN TRAIN CONSULTATION
MODELS TO CLASSIFY BEHAVIOR OF
ORGANISMS EACH FRAME.
SO IN THIS PIPELINE TWO SOURCES
OF HUMAN ANNOTATION.
IF WE WERE TRAINING MODEL
SUPERVISE WAY WE WOULD NEED
HUMAN ANNOTATION FOR KEY POINT
AS WELL AS ANNOTATION FOR
BRINGING BACK BEHAVIOR LABELS
CORRESPONDING TO BEHAVIOR OF
INTEREST SCIENTISTS LIKE TO
STUDY.
SO WHEN WE LOOK AT THESE TWO
SOURCES OF DATA, WE CAN
PREVIOUSLY LOOK AT METHODS THAT
CAN USE SUPERVISION TO HELP
REDUCE HUMAN ANNOTATION EFFORT
ON THE DATA SUPERVISION IS A
MACHINE LEARNING TECHNIQUE THAT
ALLOWS MODELS TO BE TRAINED ON
MAKE TASKS, THE FINAL DATA IS
USING HUMAN ANNOTATION.
ONE QUICK EXAMPLE OF SELF
SUPERVISION IS PREVIOUS WORK ON
DISCOVERING KEY POINTS FROM
BEHAVIOR VIDEOS.
IN THESE KEY POINTS EXAMPLES
THERE WERE NO HUMAN ANNOTATION
REQUIRED FOR DISCOVERING THE KEY
POINTS BECAUSE OUR MODELS WERE
TRAINED TO KEY POINTS USING
SELF-SUPERVISE SIGNAL FOR
RECONSTRUCTING THE AGENT
MOVEMENT FROM DATA.
GOING TO A LITTLE MORE DETAIL,
OUR WORK ON QUANTIFYING BEHAVIOR
USING A METHOD CALLED TASK
PREVAILING OUR TESTS WORK OUR
GOAL WAS TO IDENTIFY THE
REPRESENTATION LEARNING
FRAMEWORK FOR TRAINING MODEL
USING NEURAL NETWORKS AS WELL AS
FEATURE DESIGN WHICH ARE MOSTLY
BASED ON HUMAN (INAUDIBLE).
IN THIS FRAMEWORK THE FIRST PART
OF OUR METHOD IS SELF-SUPERVISE
SELF-TRAINING USING INPUT
TRAJECTORY DATA ITSELF WHICH
REPRESENT N. THE SELF-SUPERVISE
CASE WE MAPPED THE TRAJECTORY
DATA TO A LOWER REPRESENTATION
SPACE, REPRESENTED BY THIS BLUE
RECTANGLE ON THE SLIDE AND THEN
WE USE THAT SPACE TO RECONSTRUCT
INPUT TRAJECTORY WHICH IS
REPRESENTED BY THE RED DOTTED
LINE ON THE RIGHT HAND.
ON THE OTHER HAND OUR MODEL CAN
BE TRAINED USING CHEMO DOMAIN
KNOWLEDGE THROUGH THESE PROGRAMS
THAT CAN BE CONSTRUCTED BY
SCIENTISTS, THESE PROGRAMS ARE
CALLING -- ON THE SLIDES AND
THESE PROGRAMS REPRESENT
BEHAVIORAL ATTRIBUTES IMPORTANT
FOR IDENTIFY BEHAVIOR SUCH AS
THE ANIMALS I WILL SHOW ON THE
SLIDE, THESE PROGRAMS THINGS
LIKE SPEED OR FACING GO BETWEEN
ANIMALS AND ONCE YOU HAVE YOUR
INPUT DATA IN TERMS OF TAU AND
SUPERVISION, IN TERMS OF
PROGRAMS AND IN TERMS OF LAMBDA,
THE FRAMEWORK CAN BE TRAINED ALL
TOGETHER TO RESULT IN LOWER
DIMENSIONAL REPRESENTATION SPACE
FROM YOUR INPUT TRAJECTORY DATA
THAT HELP SEPARATE OUT THESE
BEHAVIORS OF INTEREST, THAT YOU
LIKE TO STUDY.
QUICKLY SHOWING QUALITATIVE
RESULTS, WE CAN SEE THAT WHEN WE
LOOK AT BEHAVIOR CLASSIFICATION
ERROR RAINING DATA FRACTION ON X
ACT SEIZE WE CAN SEE THAT WE
LOOK AT KEY POINT FEATURES 100%
OF THE DATA, WE SEE THAT USING
WE ACHIEVE THE SAME
CLASSIFICATION ERROR, KEY POINT
FEATURES 100% OF DATA WITH OUR
FEATURES JUST 10% DATA
CORRESPONDING TO TEN TIME
IMPROVEMENT IN EFFICIENCY.
FINALLY EARLIER TIM TALKED
IMPORTANCE OF BENCHMARKING, I
WANT TO EMPHASIZE IT IS
IMPORTANT AS WELL AS BEHAVIOR
MODELS AND PREVIOUSLY WE
INTRODUCED LARGE SCALE DATA SETS
BENCH MARKING SUPERVISE BEHAVIOR
CLASSIFICATION CONSISTING OF
MILLIONS OF FRAMES OF TRAJECTORY
DATA AS WELL AS HUMAN ANNOTATION
STUDYING SUPERVISE BEHAVIOR
MODELS.
THIS YEAR WE BENCHMARK
REPRESENTATION LEARNING MODEL
USING A DIFFERENT DATA SET
CONSISTING OF TRAJECTORY AS WELL
AS VIDEO DATA IN ORDER TO
BENCHMARK BEHAVIORAL
REPRESENTATION LEARNING AND
FINALLY I WANT TO CONCLUDE BY
SAYING WE ARE HAVING A COMMUNITY
DISCUSSION AND WORKSHOP AND
THANK YOU VERY MUCH FOR
LISTENING TO THIS PRESENTATION.
THANK YOU.
>> MY NAME IS CHRIS NIELL,
UNIVERSITY OF OREGON.
MY LAB IS INTERESTING IN
UNDERSTANDS THE NEURAL CIRCUIT
THAT GUIDE VISUAL BEHAVIOR.
PARTICULAR WE ARE INTERESTEDDED
IN ACTIVE SENSING AND IMPACT OF
MOVEMENT ON VISUAL FUNCTION AND
HOW THE VISUAL SYSTEM PROCESSING
COMPLEX NATURAL SCENES. MOST
USES A PARADIGM WHERE SUBJECT
LOOKS AT GEE METRIC STIMULI ON
COMPUTER SCREEN AND SUBJECT HAS
TO MAKE A DECISION, MOVING A
BALL LEFT VERSUS RIGHT OR GO NO
GO, IN RESPONSE TO STIMULI TO
MAKE A DECISION HORIZONTAL
VERSUS VERTICAL.
THIS IS A POWERFUL APPROACH, FOR
ONE REASON IT ALLOWS
EXPERIMENTER TO DIRECTLY CONTROL
THE VISUAL STIMULUS PRESENTING
ON A SCREEN AND WE HAVE A DIRECT
READ OUT OF THE ANIMAL BEHAVIOR
DIRECTLY QUANTIFIED TO A
PSYCHOMETRIC FUNCTION SUCH AS
THE ONE ON THE LEFT.
SO WE THINK THIS IS
EXPERIMENTALLY POWERFUL, REALLY
LACKING IN LOTS OF THINGS WE
WANT TO STUDY IN TERMS OF
NATURAL VISUAL PROCESSING.
BECAUSE THE STIMULUS PROPERTIES
AND MOTOR OUTPUT ARE ARE
DECOUPLED TO ANIMAL NATURAL
BEHAVIOR REGIME.
NOT ONLY THE FACT WE ARE SEEING
GEOMETRIC STIMULI ON SCREEN
PRESENTING NATURAL SEENS THAT IS
RICH THAN 3 DIMENSIONAL
ENVIRONMENT WE MOVE THROUGH.
THE MOTOR OUTPUT MOVING A BALL
LEFT VERSUS RIGHT IS DIFFERENT
THAN THE WAY WE USUALLY INTERACT
MOVING TOWARDS AWAY, REACHING
OUT INTERACTING WITH THINGS.
AND IMPORTANTLY, MOVEMENTS
WITHIN THE ENVIRONMENT AFFECT
THE STIMULUS THEMSELVES AS WELL.
SO MOVING TO A MORE NATURAL
STUDY OF VISION, NATURAL CONTEXT
WE MOVE TOWARDETH LOGICAL
APPROACH TAKING BEHAVIOR THE
ANIMAL PERFORMANCE IN WILD AND
TRANSPLANTING THEM INTO
EXPERIMENTAL PARADIGMS IN THE
LAB.
FIRST DEVELOPED BY JENNIFER HOY
WHO ADAPTED AD PARADIGM SHOWN
HERE.
YOU CAN SEE THE MOUSE IN BLUE,
CRICKET IN IN RED.
ONCE THE MOUSE SEES CRICKET AND
MAKES THAT DIRECT BELINE
APPROACH TOWARD LOCATION THEY
AREN'T QUITE AS GOOD CATCHING
WHEN THEY GET WILL, MAYBE TO DO
WITH THE FACT THESE ARE LAB MICE
THAT DON'T HAVE EVOLVED CAPTURE
CRICKETS BUT ADVANTAGE OF FACT
CRICKET IS EACH INDIVIDUAL
APPROACH ACTS LIKE A TRIAL IN
TYPICAL BEHAVIORAL PARADIGM SO
NOW WE HAVE THE MOUSE
INTERACTING WITH NATURAL VISUAL
STIMULUS, CRICKET.
AND PERFORMING NATURAL
BEHAVIORAL MOTOR OUTPUT
DETECTING APPROACHING AND
CAPTURING THE CRICKET.
CORRESPONDINGLY SHE DEVELOPED
WAYS TO QUANTIFY THIS BEHAVIOR
SHOWN IN UPPER RIGHT IS THE
ANGLE THAT CRICKET ANGLE OF
CRICKET RELATIVE TO MOUSE HEAD
SO HOW ACCURATELY THEY TARGET
THE CRICKET AND BOTTOM RIGHT
PERFORMANCE IS FUNCTION OF
DISTANCE FROM THE CRICKET.
THIS ALLOWS CALCULATE SOMETHING
LIKE PSYCHOMETRIC CURVE IN THE
BEGINNING BUT CONTEXT OF NATURAL
BEHAVIOR READING OUT NOT ONLY
WHAT ANIMAL SEE BUT USING TO
GUIDE BEHAVIOR.
WE USE THIS PARADIGM TO STUDY
SEVERAL THINGS INCLUDING CELL
TYPES AND SUPERIOR CALICULUS
THAT MEDIATE DETECTION VERSUS
APPROACH AND HOW THE MICE MOVE
EYES PERFORMING THE TASK.
BASED ON SUCCESS WE HAVE GONE TO
DEVELOP OTHER VISUAL BEHAVIOR
PARADIGMS BASED O ON ETHOL ETHO-
MOTION ACTS AS A QUEUE
DEMONSTRATING UPPER RIGHT AS YOU
MOVE YOUR HEAD SIDE TO SIDE
OBJECTS FAR AWAY MOVE A LITTLE
BIT, OBJECTS CLOSE UP MOVE A
LOT.
PROJECT THE BEHAVIORAL TASK BILL
PARKER A POST DOC TRAINED MICE
TO JUMP ACROSS GAPS OF DIFFERENT
DISTANCES.
YOU WILL SEE THIS HERE THE MOUSE
BOB ITS HEAD UP AND DOWN AND
JUMP ACROSS THE GAP.
THAT BOBBING HEAD UP AND DOWN IS
WHAT WE THINK GENERATES MOTION
QUEUE THEY ARE USING TO ESTIMATE
DISTANCE.
LIKEWISE ABLE TO QUANTIFY THIS
BEHAVIOR AND BOTTOM LEFT IS
SIMPLE MEASURE SUCCESS RATE
VERSUS DISTANCE, CAN USE OCULAR
QUEUES IF THEY CLOSE AN EYE THEY
PERFORM THE TASK AS WELL, THEY
DON'T CRUISER REVISION BUT
MOTION PARALAX.
WE USE ARHAM TO DEFECT MOTIF SO
THESE MOTIFS ENHANCE DURING
OCULAR PERFORMANCE OF THE TASK
SYSTEM PARALAPSE.
THERE IS A BIG CHALLENGE IN
STUDYING NEURAL PROCESSING IN
NATURAL BEHAVIOR WHICH IS ANIMAL
MOVING AROUND SO TYPICALLY WHAT
WE DO IN DIGITAL PHYSIOLOGY WE
PRESENT STIMULUS MEASURE NEURAL
RESPONSE, IN THIS CASE ANIMAL IS
MOVING WE NO LONGER HAVE CONTROL
WHAT VISUAL STIMULUS IS.
IN ORDER TO DETERMINE THE
STIMULUS ANIMAL MOVING THROUGH
THE ENVIRONMENT PHIL PARKER SET
UP A PARADIGM WITH HEAD MOUNTED
CAMERAS ONE WHICH LOOKS A IF THE
WORLD TO SEE WHAT THE PANEL IS
SEEING, ANOTHER BACK AT THE EYE
LOOKING WHERE THEY ARE WITHIN
THE VISUAL SCENE AND I USE TO
MEASURE HEAD MOVEMENTS AND
SILICON PROBES TO MEASURE
ACTIVITY.
WE GET SOMETHING LIKE THIS.
WE CAN SEE POSITION OF THE EYE,
WE CAN SEE ANIMAL IS SEEING WITH
ACTIVITY OF HUNDRED NEURONS AT
THE TIME.
YOU CAN SEE PATTERNS OF ACTIVITY
HERE WHEN ANIMAL SITTING STILL
VERSUS MOVING, POPULATION
ACTIVITY SHIFTS.
BIG ANALYSIS ON HOW WE RELAY
FREELY MOVING VIDEO TO NEURAL
ACTIVITY, GRAD STUDENT IN THE
LAB TOOK ON THIS CHALLENGE USE A
DEEP LEARNING APPROACH, MACHINE
LEARNING APPROACH, COMPENSATES
FOR EYE MOVEMENT TO CORRECT THAT
SCENE RELATIVE TO MASSES GAZED
AND ESTIMATE RECEPTOR FIELD IN
ONE FELL SWOOP.
WE CAN GET RECEPTOR FIELDS LIKE
A HEAD MIXED MOUSE BUT NOW IN
THE CONTEXT OF FREELY MOVING
MOUSE.
WE CAN EVEN PREDICT PATTERN
NEURAL ACTIVITY BASED ON WHAT
THE MOUSE IS SEEING MOVING
THROUGH THE ENVIRONMENT.
SO ALTOGETHER THIS PROVIDES A
NICE PARADIGM TO STUDY SENSORY
PROCESSING UNDERETH LOGICAL
CONDITIONS, PERFORMING A TASK,
MEASURE SENSORY INPUTS.
MEASURE NEURAL ACTIVITY AND USE
BEHAVIOR QUANTIFICATION MEASURES
TO QUANTITY OUTPUT.
NEURAL ACTIVITY AT BEHAVIOR.
WITH THAT I WILL PASS THINGS ON
TO BING.
>> HI, EVERYONE.
I'M FROM THE UNIVERSITY OF
WASHINGTON.
WE ARE GROUP OF COMPUTATIONAL
NEUROSCIENTISTS, WE ARE
INTERESTED IN CONNECTING NEURAL
PROCESSING AND BEHAVIOR
ESPECIALLY NATURAL BEHAVIOR SUCH
AS THE LENS CHRIS WAS TALKING IN
THE PREVIOUS TALK.
WHAT I WANT TO TALK ABOUT TODAY
ARE SET OF MODELS THAT REALLY
ACKNOWLEDGE THE FACT THAT
NATURAL BEHAVIORS ACTUALLY ALL
BUT NATURAL IN PARTICULAR ARE IN
INEXTRICABLY TIED TO ACTION AND
MEASURABLES OVERALL, THE ANIMAL
ACTS IN THE REAL WORLD WHICH
CHANGES IN SOME WAY AND THESE
CHANGES ARE DETECTED BY THE
ANIMAL THROUGH A SENSORY
MEASUREMENTS.
HERE THE WORLD COULD BE PHYSICAL
WORLD, COULD ALSO INCLUDES OTHER
AGENTS SUCH AS ANIMALS IN THE
SAME SPECIES OR EVEN INTERACTION
WITH ANIMALS OF DIFFERENT
SPECIES AS WELL.
SO ONE THING I'M EXCITED TO
THINK ABOUT IS NOT THAT THESE
TRACKING TECHNOLOGIES ARE
GETTING REALLY GOOD, ABILITY TO
SEE WHAT ANIMAL AND EVEN
INTERACT ANIMAL IS ALSO GETTING
BETTER.
SO THE TYPE OF MODELS WE ARE
BEING ABLE TO BUILD ACKNOWLEDGE
THE FACT THAT ALL THESE
INTERACTIONS ARE INCLUSIVE.
SO COUPLE OF EXAMPLES OF THAT,
MY LAB IS WORKING ON TO EMBRACE
THE CLOSE LOOP NATURE OF THESE
TYPES OF OF SO THE FIRST EXAMPLE
IS A BEHAVIOR KNOWN AS
(INAUDIBLE) BEHAVIOR THAT IS
DONE BY LOTS OF ANIMALS, INSECTS
AND TERRESTRIAL VERTEBRATES AND
THE LIKE.
THERE IS AN ODOR SOURCE, PIECE
OF FOOD OR MAYBE A MATE AND THE
ANIMAL IS TRYING TO FIND
LOCATION.
SO ODOR JUST THAT BLACK DOT ON
THE LEFT-HAND SIDE HERE.
SO WHEN THE ANIMAL GETS CLOSE
ENOUGH THE SEE TARGET USUAL
VISUALLY GUIDED BEFORE YOU CAN
SEE THE TARGET, JUST TRACKING
ODOR WHICH COULD BE TURBULENT
ENVIRONMENT AND INTERACTION
CHANGING LEADING TO INSULT LIKE
THAT SO THIS IS CHALLENGING
PROBLEM, IT IS DIFFERENT FROM
WHAT U YOU MIGHT BE FAMILIAR
WITH, BACTERIA CHEMOTACKSIS,
THERE IS NO GRADIENT TO SPEAK
OF.
THERE IS A REALLY LOVELY REVIEW
RECENTLY WRITTEN BY SEVERAL
AUTHORS REFERENCES ON THE BOTTOM
OF THE SLIDE THERE.
THAT HIGHLIGHT IT IS
COMPUTATIONAL DIFFICULTIES.
AND MULTI-SEASONSRY INTEGRATION,
INVOLVES NON-TRIVIAL MEMORY AS
WELL.
SO THE WAY WE WENT SOLVING THIS
PARTICULAR PROBLEM IS BY TAKING
A DEEP REINFORCEMENT LEARNING
APPROACH.
WHERE WE DEVELOPED A TURBULENT
PLUME SIMULATION, WHERE THE
PLUME IS SIMULATED AS A SET OF
POISSON DISTRIBUTED ODOR PUFFS
THAT ORIGIN NATIS FROM ORIGIN
AND GETS INFECTED DOWNSTREAM
FOLLOWING THE WIND.
SO THE LOCAL WIND DIRECTION ODOR
CONCENTRATION IS MADE AVAILABLE
TO AGENT AND AGENT THEN HAS THE
ABILITY TO EITHER MOVE FORWARD
OR (INAUDIBLE) LOCAL HERE.
THE AGENT IN THIS PARTICULAR
CASE, IMPLEMENTED AS CURRENT
NEURAL NETWORK.
WE ALSO IMPLEMENTED A CRITIC
MODEL WHERE WE TRAIN ACTOR ARM
IN USING TRIPS FROM LEARNING TO
TEACH IT TO RESPOND TO THIS
ENVIRONMENT USING ONLY LOCAL
INFORMATION TO LOCALIZE THE
SOURCE.
TO JUMP TO SOME OF THE
CONCLUSIONS, WHAT WE SEE IS THE
AGENT AS YOU CAN SEE HERE THE
BEHAVIORS ON THE LEFT HAHN SIDE,
AND THE UNDERLYING NEURAL
DYNAMICS ON THE RIGHT HAND SIDE.
WHAT I WILL HIGHLIGHT HERE ARE
COUPLE OF THINGS WE LEARNED FROM
THIS MODELING.
THE FIRST IS THAT DEEP
REINFORCEMENT AGENT CAN ACTUALLY
IMPLEMENT BEHAVIOR REALLY DO
RESEMBLE REAL INSECT BEHAVIOR
THAT DOES TASK SEARCH BEHAVIOR
CHARACTERISTIC OF THIS TYPE OF
PLUME TRACKING.
IMPORTANTLY, WHAT THIS
GENERATIVE MODEL SUGGESTED IS
COUPLE OF TESTABLE HYPOTHESES
THAT CAN BE TESTED IN ARENA.
WHAT IS REALLY COOL ABOUT THIS
APPROACH IS THAT THIS IS A TYPE
OF NATURAL BEHAVIOR WE LIKE TO
BE ABLE TO UNDERSTAND.
YOU CAN TRACK IT IN REAL LIFE IF
YOU WANT TO LARGE ARENA WITH A
PLUME AND ON THE OTHER HAND IF
YOU HAD A ANIMAL YOU CAN RYE TO
INTERROGATE NEURODYNAMICS.
BUT LOOKING AT NATURAL BEHAVIOR
ON ORDER OF METER AND KILOMETER
AND HAVING ACCESS TO
NEURODYNAMICS IS NOT
EXPERIMENTALLY TRACTABLE RIGHT
NOW.
SO WHAT I LIKE ABOUT THE MODEL
IS IT PROVIDES A BRIDGE BETWEEN
BEHAVIORAL EXPERIMENTS AND
UNDERLYING NEURODYNAMICS IN A
WAY THAT WE CAN TIE TOGETHER
EXPERIMENTS IN A REALLY NICE
WAY.
ANOTHER SET OF EXPERIMENTS WE
ALSO TRIED TO UNDERSTAND IN THIS
WAY ARE DETAILED UNDERSTANDING
OF SOME POST DYNAMICS.
IN THIS CASE THIS IS A WALKING
FLY OPPOSED TO FLYING FLY.
WE HAVE TAKEN THE SAME KIND OF
CLOSE LOOP FLEXIBLE MODELING
APPROACH HERE WHERE WE CAN USE
COMPUTATIONAL MODELS TO TIE
TOGETHER DIFFERENT EXPERIMENTS
OF THE SAME UNDERLYING BEHAVIOR,
IN THIS CASE WALKING SO WE CAN
HAVE A DEI WILL TAD MODEL OF THE
PHYSIOLOGICAL PROCESS OF THE
PROPRIA ACCEPTOR MODEL AND
WHATEVER THE DYNAMICS ARE AND
HOPE TO HAVE SIMILARLY DETAILED
PHYSIOLOGICAL UNDERSTANDING OF
MUSCLE MECHANICS AND
BIOMECHANICS AS WELL.
SO THIS IS JUST A COUPLE OF
EXAMPLES WE WORKED ON BUT WHAT I
AM TRYING TO CONVEY IS THESE
CLOSE LOOP MODELS WILL BE
CENTRAL IN EFFORT TO GO FROM
TRACKING TO UNDERSTANDING OF THE
UNDERLYING NEURAL MECHANISMS.
>> HI EVERYONE MY NAME IS TIM
GENTNER, UNIVERSITY OF
CALIFORNIA SAN DIEGO AND MY LAB
IS INTERESTED IN NEURAL BASES OF
COMMUNICATION ON PERCEPTUAL AND
ALSO PRODUCTION SIDE, TRYING TO
MODEL BEHAVIOR AND THE
UNDERLYING NEUROPHYSIOLOGICAL
MECHANISMS IN A WAY THAT CAN
SERVE AS MODEL FOR BRAIN
COMPUTER INTERFACE.
WHAT I WANT TO DO TODAY IS TO
TAKE YOU THROUGH A RANGE OF
DIFFERENT STUDIES THAT WE HAVE
BEEN APPLYING VARIETY OF MACHINE
LEARNING METHODS TO GET BETTER
HANDLE ON THE STRUCTURE OF THESE
COMPLICATED COMMUNICATION SIGNAL
THAT SONG BIRDS PRODUCE AND
LEARNED SONGS IN WAY WE HAVE
BEEN ABLE TO USE THOSE MEASURES
TO BUILD BEHAVIORAL MODELS AND
THEN DRIVE INTO VARIETY OF
NEUROPHYSIOLOGICAL QUESTIONS.
MOST DATA I WILL SHOW YOU IS
PUBLISHED, I WILL BE MOVING AT A
PRETTY HIGH LEVEL BUT WHAT I
WANT TO DO IS POINT OUT COUPLE
OF DIFFERENT CHALLENGES THAT
EXIST IN THIS SPACE.
FIRST SONG BIRDS ARE PROLIFIC,
ABOUT 4500 DIFFERENT SPECIES OF
SONG BIRDS, THE SONGS THAT
DIFFERENT SPECIES SING ARE VERY,
VERY DIFFERENT.
SO WHAT WE SET OUT TO DO IN
SERIES OF STUDIES PUBLISHED
TOGETHER WITH TALENTED STUDENT
KIM SINGBURG WAS CREATE METHODS
OR ASSEMBLE SET OF EXISTING
METHODS THAT ALLOWED US TO
EXAMINE DIVERSITY ACROSS WIDE
RANGE OF SPECIES AND ONE OF THE
QUESTIONS THAT WE SET OUT TO
GAIN INSIGHT TO INITIALLY WAS
THE ASSUMPTIONS THAT GO IN TO
UNDERSTANDING COMPLEX BEHAVIOR
IN GENERAL.
ONE OF THE BIG QUESTIONS IS
WHETHER OR NOT TO BUILD A
REPRESENTATION OF THAT SIGNAL OR
A MORE CONTINUOUS REPRESENTATION
OF THE SIGNAL.
AND TURNS OUT THAT A LOT OF THE
METHODS THAT ARE AVAILABLE MAKE
NUMBER OF ASSUMPTIONS THAT ARE
IMPORTANT TO CONSIDER WHEN YOU
ARE PROFESSING COMPLICATED PROF
BEHAVIORS DOWN INTO SMALLER
DIMENSIONAL LATENT SPACES.
ONE OF THOSE IS THE DISTINCTION
BETWEEN WHETHER OR NOT WE LOOK
AT GLOBAL VARIANTS OR LOCAL
VARIANTS IN THIS STRUCTURE OF
THE SIGNAL BOTH OF THOSE
POTENTIALLY RELEVANT AND I PUT
UP THIS SLIDE AS WAY OF POINTING
OUT THAT DECISIONS ABOUT WHETHER
TO REPRESENT GLOBAL OR LOCAL
VARIANTS USING SOMETHING
STRAIGHT FORWARD LIKE PRINCIPLE
COMPONENTS ANALYSIS OR MORE
LOCAL VARIANTS LIKE U MAP, ON
THE STRUCTURE OF THE LATENT
SPACE AND WHAT YOU ARE LOOKING
AT HERE ON THE LEFT HAND SIGH OR
RIGHT HAND SIDE OF THE FIGURE,
ARE PROJECTIONS OF THE SAME SET
OF LOCAL SIGNALS FROM A SINGLE
SPECIES, INTO FOUR LATENT SPACES
AND AS YOU CAN SEE THE
REPRESENTATIONS YOU GET OUT
UNDER THOSE CIRCUMSTANCES CAN BE
QUITE DIFFERENT.
IF WE TAKE THOSE LATENT SPACES
SETTLED ON A SET OF ASSUMPTIONS
THAT WE THINK ARE REASONABLE TO
ME, WE CAN CONSIDER ADDITIONAL
PROBLEM WHETHER OR NOT WE WANT
TO LOOK AT A DISCRATIZED VERSION
OF SIGNALS ANIMAL PRODUCING IN
THIS SPACE AND SHOW YOU SIGNAL
ON THE TOP FROM BIRD THAT SINGS
ELABORATE SONGS AND THEN IN THE
CENTER IS TO CREATE CONTINUOUS
REPRESENTATIONS OF THAT SONG
PROJECTED USING SMALL WINDOWS
INTO A U MAP REPRESENTATION
TAKING A LOOK AT MULTIPLE BOUTS
FROM LEFT TO RIGHT OF A SINGLE
MALE, SINGING MANY DIFFERENT
SONGS, AND WHAT YOU CAN SEE IS
THAT THERE IS A LOW DIMENSIONAL
TRAJECTORY WHERE VOCALIZATION
MOVES THROUGH THIS LATENT SPACE.
YOU CAN SEE REPEATING ELEMENTS
IN THE LOW DIMENSIONAL
TRAJECTORIES THAT GIVE US
INDICATION OF THIS COMPLICATED
STRUCTURE PROJECTED DOWN INTO A
SMALL NUMBER OF DIMENSIONS.
YOU CAN ALSO TAKE A DISCRATIZING
APPROACH INTO THIS VOCAL SIGNAL
INSTEAD OF LOOKING AT THE
CONTINUOUS SIGNAL YOU CAN GROUP
THESE CONSTELLATIONS OF SIMILAR
BEHAVIORS INTO SMALLER SPACES,
I'M SHOWING YOU NOW ON THE LOWER
ROW A REPRESENTATION OF
(INAUDIBLE) COMPRESSED TO LATENT
SPACE, ONCE YOU HAVE LATENT
SPACE REPRESENTATIONS YOU CAN
PERFORM A VARIETY OF DIFFERENT
CLUSTERING ALGORITHMS ON THEM
AND PULL OUT TRANSITION
MATRICES, THESE ALLOW YOU TO
CREATE A SAFE SPACE BASED
REPRESENTATION OF SIGNAL ITSELF.
THESE STATE SPACE
REPRESENTATIONS OF THE SIGNAL
ARE REALLY USEFUL IN PARTICULAR
IT LED TO REALLY IMPORTANT
UNDERSTANDING WHICH IS THAT
SIMPLY REPRESENTING SIGNAL IN A
COMPACT LATENT SPACE OR LOW
DIMENSIONAL COMPRESSION ISN'T
ENOUGH.
WHAT WE WANT TO HAVE IS A MODEL
OF BEHAVIOR AS WELL AND WHAT I'M
SHOWING YOU HERE ON THE
LEFT-HAND SIDE ARE THREE
DIFFERENT WAYS OF THINKING ABOUT
THE REPRESENTATION OF STATES
SPACE VOCALIZATIONS THAT EXIST
IN TIME SO YOU CAN THINK ABOUT
RELATIONSHIPS OF DIFFERENT
STATES IN TIME MIGHT HAVE TO ONE
ANOTHER AND PREDICTABILITY OF
THOSE RELATIONSHIPS ACROSS TIME.
WHAT WE ARE ABLE TO FIND IN THIS
PARTICULAR INVESTIGATION IS THAT
THOSE RELATIONSHIPS CAN BE QUITE
CONVENIENTLY EXPRESSED IN THREE
DIFFERENT WAYS SHOWN ACROSS THE
LOWER PANEL ON THE LEFT-HAND
SIDE IN RED YOU SEE A
HIERARCHICAL REPRESENTATION
BETWEEN THE STATE SPACES THAT
GIVES RISE TO A SCALE AND
VARIANT POWER LAW IN GREEN IN
THE CENTER YOU SEE A MARK OFF
REPRESENTATION THAT GIVES RISE
TO EXPONENTIAL FALL OFF IN
INFORMATION ACROSS TIME AND THEN
IN BLUE YOU SEE A COMBINATION OF
POWER LAW AND EXPONENTIAL MODEL
YOU CAN SEE EARLY EXPONENTIAL
DECAY FOLLOWED BY FLATTENING
OUT.
THE INTERESTING THING TO POINT
OUT, THE SAME KIND OF
REPRESENTATION, SAME STRUCTURE
STATISTICAL STRUCTURE OF
INFORMATION CAN BE OBSERVED IN
HUMAN SPEECH AND IN BIRD SONG.
SO WHAT I'M SHOWING YOU ON THE
LEFT-HAND SIDE IS A
REPRESENTATION FROM TWO
DIFFERENT HUMAN LANGUAGES
ENGLISH AN JAPANESE, AND THEN
FROM TWO DIFFERENT SPECIES OF
SONG BIRDS, A VERIO AND EUROPEAN
STARLING SHOWING THAT YOU GET
LOW SHORT DISTANCES YOU SEE
EXPONENTIAL DECAY IN THE
INFORMATION BETWEEN ELEMENTS AND
THAT LONGER DISTANCE POWER LAW
DECAY SO THIS SUGGESTED FROM
DEEP FUNDAMENTAL UNDERLYING
SIMILARITIES BETWEEN THE WAY
HUMANS ARE STRUCTURING THEIR
VOCAL SIGNAL AND WAY OTHER
ANIMALSES ARE STRUCTURING VOCAL
SIGNALS AS WELL.
YOU CAN ALSO THINK ABOUT THE
BENEFIT OF COMPRESSING INTO A
LATENT SPACE, NOT JUST IN TERMS
OF GIVING YOU THIS MORE COMPACT
CATEGORICAL REPRESENTATION OF
SIGNAL BUT PROVIDING ITSELF A
DIRECT MODEL OF THE SIGNAL.
WE HAVE BEEN ABLE TO USE THE
POWER OF AUTO ENCODERS IN THIS
WAY TO PROJECT TRAIN THEM ON
LARGE CORPUSES OF BIRD SONG,
REJECT THOSE INTO SMALL
DIMENSIONAL LATENT SPACES AND
ONE THING WE FIND ABOUT BIRD
SONG IS THAT OFTENTIMES SIGNAL
ARE SPARSE WHICH IS WAY OF
SAYING YOU MIGHT HAVE ONE SOUND
THAT LIVES IN ONE PORTION OF THE
LATENT SPACE AND ANOTHER SOUND
THAT LIVES IN ANOTHER SOUND IN
ANOTHER LATENT SPACE AND NO
NATURALLY OCCURRING SOUNDS THAT
EXIST BETWEEN THOSE TWO
CATEGORIES.
BUT WE CAN USE LOW DIMENSIONAL
STRUCTURE OF AUTOINENCODER TO
INTER COLLATE BETWEEN THE LOW
DIMENSION -- BETWEEN THOSE TWO
CATEGORIES AND APPLY
PSYCHOPHYSICAL METHODS NOW TO
DEVELOP A VERY DETAILED
UNDERSTANDING OF THE WAY BIRDS
RECEIVE CHANGES -- PERCEIVE
CHANGES ACROSS THESE COMPLEX
COMMUNICATION SIGNAL.
I WON'T GO INTO THE DETAILS OF
THIS HERE.
BUT IT IS A WAY OF UNDERSTANDING
PERCEPTION USING THE MACHINE
LEARNING, IT IS AS A MODEL FOR
STATISTICAL STRUCTURE OF THE
SONG THAT ALLOWS US TO GENERATE
NOVEL INSTANCES THAT LIVE IN
THAT SAME NATURAL STIMULUS SPACE
BUT MIGHT NOT BE OBSERVABLE OUT
IN THE WILD.
OF COURSE THE BIG ADVANTAGE OF
USING SONG BIRDS IS THAT WE CAN
TODY THE SIGNAL BOTH FROM A
PRODUCTION AN PERCEPTION
STANDPOINT IN THE INTEREST OF
TIME I WON'T GO INTO DETAILS
HERE, WE HAVE BEEN USING PIXELS
AND OTHER LARGE ARRAYS TO REPORT
BIRDS WHILE PRODUCING
VOCALIZATIONS, USING OUR
UNDERSTANDING OF THE TEMPORAL
STRUCTURE OF THE MODEL IN ORDER
TO DESCRIBE THE SIGNAL AND THEN
USE THOSE DESCRIPTIONS TO
UNDERSTAND PERCEPTION DIRECTLY.
THANK YOU VERY MUCH.
>> SO I WANTED TO REMINDER THAT
THERE IS A Q&A TAB ABOVE THE
CHAT ON YOUR SCREEN SO IF YOU
HAVE ANY QUESTIONS ABOUT THESE
TALKS, PLEASE QUESTION I SEE
SOME ARE COMING IN NOW BUT JUST
IN CASE NOW IS TIME TO PUT THOSE
QUESTIONS IN AND WE WILL GET TO
THEM AFTER WE HAVE A BRIEF PANEL
DISCUSSION
>> ANY QUESTIONS WE DEEM
IMPORTANT FOR THIS TOPIC.
SO THE FIRST QUESTION I WANT THE
START WITH GIVEN ALL THESE
TECHNOLOGIES THAT WE PRESENTED,
GIVEN THAT SCHEMATIC I SHOWED
WAS HUGE SYSTEM RENAISSANCE
TECHNOLOGY, WHAT ARE WE STILL
MISSING IN TERMS OF TECHNOLOGY
FOR BEHAVIORAL MEASUREMENT?
SO SO I WILL START THERE.
IT IS WHERE BROAD QUESTION
ANYONE HAVE ANYTHING TO SAY?
JAN AND CHRIS ARE READY TO GIVE
PERSPECTIVE ON THIS.
>> I CAN GIVE A LITTLE MY
PERSPECTIVE FROM THE LARGE
ANIMAL RECONSTRUCTION.
OUR MODELS ARE NOWHERE GOOD
ENOUGH YET.
WE ARE ONLY STARTING TO GET
TOWARDS GOOD RELIABLE
RECONSTRUCTIONS OVER LONGER
PERIODS OF TIME.
I THINK IF WE ARE PERCEIVE
FUTURE WE NEED MODELS LIKE HUMAN
MODELS, THAT HAVE THE SAME KIND
OF ACCURACY THAT HAVE THE SAME
KIND OF EASE OF USE WHERE PEOPLE
CAN PLUG IN DATA AND EVERYTHING
IS AGNOSTIC, BACKGROUND AND
CONTEXT INFORMATION AND SMALL
OCCLUSIONS DON'T MATTER AND IT
WORKS OUT AT THE BOX.
WE ARE NOT THERE YET.
A LOT OF USs SPECIALRY HERE IN
THIS PANEL BUT ALL CROSS THE
GLOBE ARE WORKING ON THESE
SOLUTIONS AND JENNIFER'S WORK IS
A WONDERFUL EXAMPLE OF BRIDGING
THE GAP AND TRYING TO MAKE IT
EASIER FOR THE USER TO GET
RELIABLE MODELS GOING.
BUT AS JENNIFER ALSO NOTED, IN
HER PAPER, THE GENERALIZATION IS
STILL NOT PERFECT.
AND ALL THESE DEEP LEARNING
MODELS ON THE FRONT END, THEY DO
RELY ON SIMPLE FACT THAT
EXAMPLES HAVE TO BE LEARNED.
SO WE NEED GIGANTIC DATA SETS.
WE ARE NOT THERE YET.
>>PROFESSOR: SO BIG SOLUTION IS
BIG DATA?
>> I DON'T THINK BIG SOLUTION IS
BIG DATA.
THIS IS JUST FRONT END.
WHAT I'M TRYING TO SAY IS
BASICALLY IF WE HAVE BING
WORKING ON PHENOMENAL MODELS AND
REALLY TRYING TO MAKE SENSE OF
THESE DATA SETS, TRYING TO LINK
THEM TO NEURAL ACTIVITY, WE NEED
TO MAKE SURE THAT WE CAN PROVIDE
HER WITH THE TYPE OF CLEAN DATA
THAT ACTUALLY IS USEFUL FOR HER
TO ANALYZE.
SO ON THE FRONT END NOT ONLY IS
THE MODELING MISSING BUT WE
HAVEN'T EVEN FULLY SOLVED OR
RESOLVED THE PROBLEM OF ACTUALLY
PROVIDING THE TYPE OF MODELS
NECESSARY.
PHENOMENAL JOB FOR RODENTS FOR
EXAMPLE, OUR EFFORTS ARE BABY
STEPPED IN THE RIGHT DIRECTION
BUT THERE IS MANY YEARS OF WORK
TO BE DONE THE MAKE MODELS
EXTREMELY AGNOSTIC.
AND TO PUT A DREAM OUT THERE IN
A PANEL I CAN DO THAT.
IS ONE DAY I WANT THESE MODELS
TO RUN ON MY SMART PHONE, I WANT
TO BE ABLE TO RUN INTO THE
JUNGLE AND I WANT SOME OUTPUT TO
TELL ME WHAT OR RANGE TANK IS
DOING IN LARGE GROUP OF ANIMALS,
POTENTIALLY NOT WHAT I WILL DO
IN THE FUTURE BUT ETHOLOGISTS
WOULD LOVE DOING THAT.
>> CHRIS YOU WERE GOING TO SAY
SOMETHING?
>> I WAS GOING TO FOLLOW ON IN
TERMS OF GETTING THIS DATA THAT
WE NEED IS THE WHOLE RANGE OF
MULTI-MODAL DATA THAT GOES ALONG
WITH BEHAVIOR.
SO HUGE ADVANCES IN TRACKING AND
ANIMALS ALONG WITH THAT ARE
THINGS LIKE MICROMOVEMENT SO MY
NEXT DOOR NEIGHBOR HAVE SHOWN
MICE MOVE THEY'RES WHEN TRYING
TO LOCALIZE SOMETHING WITH
AUDITORY QUEUES AND FOR US ON
THE SENSORY SIDE NOT JUST
QUANTIFYING ANIMAL DOING BUT
WHAT THE WHOLE ENVIRONMENT IS
DOING WHAT IS COMING TO ANIMAL.
TWOING WITH THAT IS THE TOOL TO
LINK THESE UP, NOT JUST FROM
ACTION TO THE NEURAL ACTIVITY
BUT TOGETHER ENVIRONMENT ANIMAL
AND NEURAL ACTIVITY AND BEING
MENTIONED CLOSING THAT LOOP
BECAUSE THE ANIMAL ACTS ON THE
ENVIRONMENT TO SEE HOW ALL THESE
FIT TOGETHER.
THAT IS WHAT NATURAL BEHAVIOR
IS.
SO MUCH WHAT WE DO THINK ABOUT
IS STIMULUS RESPONSE BEHAVIOR
WITH THAT CLOSE LOOP BEHAVIOR IS
WHAT IS INTERESTING.
>> I WILL ADD ONE MORE SHORT
COMMENT.
I LOVE EVERYONE -- EVERYTHING
THAT JAN AND CHRIS JUST SAID BUT
I THINK EVEN THE SYMPOSIUM IS
CALLED TRACKING TO
UNDERSTANDING, THE FACT THAT
HUMANS ARE PARTICULARLY VISUAL
CREE CHARS DOESN'T MEAN ALL
ANIMALS ARE.
SO THERE IS A LOT MORE IMPORTANT
BEHAVIOR THAT MEETS THE EYE.
SO FOR EXAMPLE, OUR ABILITY TO
MEASURE ODORS IS VERY POOR
COMPARED TO ABILITY TO BUILD
BETTER CAMERAS.
THAT IS SUPER IMPORTANT TO LOTS
OF ANIMALS.
SO IF WE WANT TO UNDERSTAND
NATURAL BEHAVIOR THERE IS MORE
TECHNOLOGY THAT IMMEDIATE TO BE
BUILT IN ADDITION TO WHAT JAN
SAID ON THE FRONT END, FUSION
TECHNOLOGIES MORE TO BE BUILT ON
THE SOFTWARE AND HARDWARE END
AND OTHER SENSORY MODALITIES AS
WELL.
>> I AGREE WITH THESE COMMENTS
AND I THINK IT IS WONDERFUL TO
SEE DEVELOPING TECHNOLOGIES.
WE ALSO HAVE TO BE FOLLOWING ON
BING'S INSIGHT, WE HAVE TO BE
CAREFUL HOW WE DIRECT RESOURCES
IN TERMS OF JUST BUILDING THINGS
THAT CAN TAKE IN MORE DATA.
PART OF THAT MEANS THAT THERE
ARE TRADITIONS, IN ETHOLOGY YOU
CAN GO BACK THE VON -- TO GET
INSIGHT INTO DIFFERENCES THAT
DIFFERENT WAYS DIFFERENT ANIMALS
EXPERIENCE THE WORLD AND
CONTEMPORARY PSYCHOLOGY FOR ALL
ITS OPERATIONALIZATION AND FOCUS
ON MECHANISM TELLS US A LOT
ABOUT THE WAY BOTH SENSORY AND
MOTOR SYSTEMS CAN BE SELECTIVE
IN THEIR ATTENTIONAL MECHANISMS
OR IN THE AFOR DANCE THEY PLACE
ON THE WORLD.
PART OF WHAT WE NEED TO DO GOING
FORWARD IS THINK ABOUT
ABSOLUTELY EXPANDING THE SCOPE
OF WHAT WE CAN MEASURE BUT DOING
IT IN A WAY THAT BRINGS IN
KNOWLEDGE THAT EXISTS ABOUT
BEHAVIOR IN THESE OTHER DOMAINS
SO THAT WE DON'T END UP, IF OUR
GOAL IS TO HAVE SOMETHING ON
SMART PHONE THAT RUNS WE NEED TO
BE SELECTIVE ABOUT WHAT ENDS UP
THERE THERE ARE GOOD MODELS OUT
THERE, FIELDS TO DEDICATEDDED TO
THAT QUESTION.
THAT THE MACHINE LEARNING
ENGINEERING APPROACH HASN'T
SYNCHRONIZED WITH IN A REALLY
COMPELLING WAY.
>> THAT BRINGS US TO ANOTHER
QUESTION, SORRY JENNIFER.
>> I WAS -- YOU CAN GO TO THE
QUESTION, AND I -- AFTERWARDS.
>> IN CONTEXT OF NEW QUESTION
WHICH IS WE WANT TO DISCUSS WHAT
ARE BIGGEST GAPS BETWEEN TOOL
MAKERS AND PRACTICERS AND WHAT
DO WE NEED TO DO TO MAKE SURE WE
FOSTER RELATIONSHIPS CONTINUE TO
DELIVER RESULTS YOU HAVE ALL
BEEN MENTIONING.
SO THAT IS SOMETHING I WANT TO
ADDRESS, EARLIER I THINK TIM YOU
HAD A GOOD POINT IN THAT RIGHT
NOW THERE IS A LOT OF MACHINE
LEARNING RESEARCH THAT MAY NOT
BE CONNECTED TO THE DOWNSTREAM
SCIENTIFIC QUESTIONS OR
DOWNSTREAM BEHAVIOR WE WANT TO
GET FROM THESE.
ONE GAP THAT I SEE AT LEAST FROM
THE COMPUTER SCIENCE
PERSPECTIVE, IS THAT THERE IS SO
MUCH DEVELOPMENT IN COMPUTER
SCIENCE SPACE THESE LARGE SCALE
STANDARDIZED DATA SETS FOR
EXAMPLE CLASSIFICATION YOU GUYS
OFFER UP AND I THINK HAVING
THESE LARGE SCALE DEVELOPING
IDEAS THAT CAN BE HELPFUL FOR
MACHINE LEARNING COMMUNITY SO
THAT WHEN WE ARE DEVELOPING
THESE TOOLS WE CAN MEASURE IF
OUR MODEL IS DOING BETTER THAN
TOOLS AND WE CAN UNDERSTAND IF
THERE IS ANY GAPS IN
DEVELOPMENT.
SO WE MOVE ON TO NEW SENSOR
MODALITIES, THESE NEW ORGANISMS,
NEW SCIENTIFIC QUESTIONS, IT
WILL BE REALLY GOOD TO THINK
ABOUT HOW WE CAN BETTER CONNECT
PRACTICERS TO NEEDS OF TOOL
BUILDERS SO WE CAN BUILD MODELS
THAT MAKE THESE CONNECTIONS YOU
GUYS WERE MENTIONING.
>> ONE MAJOR THING THAT HAS COME
UP IN MY CAREER THE LAST COUPLE
OF YEARS ALSO WITH OUR OTHER
COLLABORATORS IS IT IS NOT
ALWAYS TRIVIAL FOR LAB LIKE MY
SIZE TO BE ABLE TO HELP THE
OTHER LABS OUT THERE TO BE ABLE
TO HELP THE PEOPLE THAT WANT TO
IMPLEMENT TOOLS WE DEVELOP.
THIS IS INCREDIBLY UNFORTUNATE
AND NOT MY DESIGN TO BE
GATEKEEPER BUT SOME OF THE TOOLS
WE PRODUCE ARE SO COMPLEX SO
LARGE, THAT THERE INCREDIBLY
DIFFICULT TO SHIP.
I SEE THAT HAPPENING IN A LOT OF
DOMAINS OF ANIMAL BEHAVIORAL
CLASSIFICATION, THAT WE ARE
BUILDING THIS INFRASTRUCTURE
ALMOST LIKE PYTHON MT. BEGINNING
WAS NOT MEANT FOR WHAT IT IS
DOING TODAY AND NOW IT IS A
CONGLOMERATE OF THINGS TO EACH
OTHER AND IT BECOMES
OVERWHELMING TO ME AND I WANT TO
GO BACK BEFORE BUT WHAT I'M
TRYING TO SAY IS WE HAVE HAVE
CREATED A MONSTER WITH ALL THESE
TOOLS TOGETHER AND WE GET TO GET
TOGETHER AND HEAR WHAT WORKS HOW
DOES IT WORK FOR PEOPLE AND HOW
WOULD IDEAL WORK FLOW LOOK LIKE
IN THEIR PLAN LABS TO COME UP
WITH A BETTER SOLUTION?
>> I GUESS RELATED TO THAT
EVERYONE WANTS TO MEASURE
SOMETHING DIFFERENT, BEHAVIOR
WHICH MAKES IT VERY COMPLEX.
NOT JUST THINK ABOUT DEVELOPMENT
OF NEURAL RECORDING TECHNOLOGIES
EARN CAN AGREE WANT SOMETHING TO
MEASURE AND ACTION POTENTIAL
RANGE.
THIS PARTICULAR CASE BEHAVIORAL
QUANTIFICATION IS COMPLEX AND
CUSTOMIZABLE AND SO HOW WE RALLY
BEHIND POTENTIALLY STANDARD
DEFINITIONS TO SIMPLIFY THESE
TECHNOLOGIES IS AN OPEN
QUESTION.
ANYONE HAVE IDEAS MAKING THE
TECHNOLOGY MORE ACCESSIBLE TO
THE COMMUNITY?
>> I THINK --
>> AT THE RISK OF --
>> SORRY.
>> THERE IS SMALL LAG, SORRY.
AT THE RISK OF KICKING THE CAN
FARTHER DOWN THE ROAD I THINK A
CRUCIAL PIECE THAT WE CANNOT
IGNORE IS ACTUALLY EDUCATING NOT
JUST COMPUTATIONAL NEUROSCIENCE
TOOL BUILDERS AND ALL
NEUROSCIENTISTS AND
COMPUTATIONAL TECHNIQUES.
ESPECIALLY RECENT YEARS THERE
HAVE BEEN SURGEONS OF
EXPERIMENTALISTS WANTING TO GAIN
MORE COMPUTATIONAL SKILLS AND
THAT IS WONDERFUL.
AND I THINK EFFORTS LIKE LOTS OF
SUMMER SCHOOLS, LOTS OF PEOPLE
WITH COURSES, LARGE EFFORTS LIKE
NEUROMETRIC ACADEMY HAVE COME A
LONG WAY IN TERMS OF EDUCATING
EVERYONE AND COMPETENCY OF -- SO
IT IS NOT JUST ON THE TOOL
BUILDERS TO MAKE TOOLS MORE
ACCESSIBLE IT IS ON THE
PRACTICERS AND END USERS TO BE A
LITTLE MORE FLEXIBLE IN IN TERMS
OF MEETING THE TOOLS WHERE THEY
ARE AT.
MAKING THEM DO WHATEVER THEY
WANT TO DO.
THAT'S GOT TO BE PART OF THE
SOLUTION.
>> JUST TO JAN'S POINT, I THINK
THAT PART OF THE ANSWER LIES IN
MOVEMENT AWAY FROM THE FULL
STACK LABORATORY APPROACH.
THAT MEANS BUILDING TEAMS AND
MEANS BUILDING TEAMS THAT SPAN
COMPUTATION IN NEUROSCIENCE OR
COMPUTATION IN ENGINEERING OR
COMPUTATION ENGINEERING AND
NEUROSCIENCE.
SO THAT WE ARE BRINGING IN
PEOPLE WHO HAVE EXPERTISE IN
MOVING DEVELOPMENT SOFTWARE TO A
PRODUCTION LEVEL STANDARD THAT
CAN HELP US TO CREATE DATA SETS
THAT ARE SHAREABLE AND OFFER
SOME KIND OF UNIFORMITY FOR
FUTURE DEVELOPMENT NOT THAT WE
WANT TO DO SCIENCE ON UNIFORM
DATA SETS, THAT'S THE OPPOSITE
APPROACH THAT I WOULD TAKE.
BUT I THINK THAT IN TERMS OF
MAKING THE TOOLS ACCESSIBLE THAT
REALLY GOING TO BE THE ONLY WAY
THAT WE DO IT.
POURING MORE RESOURCES INTO A
SINGLE LAB THAT IS BUILDING
SOMETHING AS OPPOSED TO GROUPS
IS NOT GOING TO REALLY BENEFIT.
>> CHRIS.
>> I'M SEEING A PARALLEL HERE
BETWEEN DEVELOPMENT OF TOOLS AND
PEOPLE WHO WERE NECESSARILY
COMPUTATIONALLY NEED TO USE THEM
WITH WHAT HAPPENED 15 YEARS AGO
IN SYSTEMS NEUROSCIENCE IN
OPTOGENETICS AND VIRAL METHODS
CAME OUT AND PEOPLE WHO WERE
MONKEY PHYSIOLOGISTS HAD TO
LEARN WHAT A SEROTYPE OF VIRUS
WAS, WE WERE TEAMING UP WITH THE
MOLECULAR BIOLOGIST DOWN THE
HALL WEI TO MAKE CONSTRUCTS AND
OVER TIME THAT KNOWLEDGE BECAME
COMMON.
THE FIRST TIME I WROTE A GRANT I
HAD TO EXPLAIN WHAT CRE LOX IS.
I DON'T THINK YOU HAVE TO DO
THAT ANY MORE.
TRAINEES SOME UP, THESE ARE
ESTABLISHED AND ALSO THE
STREAMLINING THE TECHNIQUES AND
YOU CAN BUY VIRUSES HAVE FROM AD
GENE AS OPPOSED TO VIROLOGIST
DOWN THE HAUL MAKE IT SO IT IS A
LITTLE BIT OF SITE WITHIN
ITSELF.
>> THAT WILL HAPPEN ORGANICALLY?
OR WAS THERE SOMETHING --
(OVERLAPPING SPEAKERS)
>> I THINK MENTIONED NOW THERE
IS THE NEUROMAX AND THERE'S
VENUES FOR PROVIDING THAT
EDUCATION THE SAME WAY THINGS
POPPED UP 15 YEARS AGO WITH
SUMMER SCHOOLS AND MOLECULAR
GENETICS.
SO SON.
SO THERE NEEDS TO BE CONCERTED
EFFORT BUT ALSO I THINK
HOPEFULLY SOME OF THESE WILL
HAPPEN AS THINGS GET STREAMLINED
AND ESPECIALLY MORE USERS ADOPT
AND THERE BECOMES COMMUNITIES
AROUND THESE.
>> JAN YOU WERE GOING TO ADD
SOMETHING?
>> ALL I WANT TO ADD IS ONE OF
THE THINGS I SAW THAT FASCINATED
ME, ONE OF THE RIGHT STEPS IN
THE RIGHT DIRECTION IS I VISITED
SALK AND -- ONE OF ORGANIZERS OF
THIS PANEL AS WELL, WHO IS
REALLY TAKING ON A HE ROW WICK
JOB OF ESTABLISHING -- HEROIC
JOB ESTABLISHING A RAPPORT TO DO
THESE TYPES OF MEASUREMENTS FOR
LABS AND INVESTIGATORS AT THE
SALK.
THE SAME THING HAPPENS AT A LOT
OF OTHER INSTITUTIONS, YOU DON'T
BUY A HIGH FIELD NMR MAGNET
WITHOUT HAVING A NMR PHYSICIST
AROUND.
WITHOUT HAVING A RADIO FREQUENCY
PHI SISSIEST AROUND.
WE HAVE -- PHYSICIST AROUND.
WE HAVE TO BELING TO MAKE THOSE
INVESTMENTS AND HAVE THIS
EXPERTISE SPREAD AROUND EACH
SINGLE LAB CAN'T POTENTIALLY
PULL OFF THESE PROBLEMS ON THEIR
OWN.
THAT GOES BACK TO WHAT BING SAID
IN THE BEGINNING.
WE NEED TO LEARN A LANGUAGE AND
WE NEED TO BE ABLE TO
COMMUNICATE WITH EACH OTHER AND
ACTUALLY -- YEAH.
>> BEFORE WE MOVE TO AUDIENCE
QUESTIONS ONE OTHER IMPORTANT
THING TO DO SINCE WE ARE GOING
FROM TRACKING TO UNDERSTANDING,
TALK ABOUT UNDERSTANDING PART.
YOU ARE PRIMARILY TALKING THE
TRACKING AND MEASUREMENT PART SO
WHAT IS NEEDED IN ORDER TO GET
TO AN UNDERSTANDING, IN TERMS OF
MEASUREMENTS AND WHAT ARE THE
TOP PRIORITIES FOR THEORY AND
MODELING.
USING THESE TYPES OF
MEASUREMENTS.
ANYONE?
>> I HAVE ALREADY GIVEN MY
PERSPECTIVES, I WILL DO A SHORT
VERSION HERE.
WE CAN BUILD IT AND FEEL LIKE
I'M INTERESTED IN SOMETHING.
>> I GUESS -- (OVERLAPPING
SPEAKERS)
>> I THINK FROM THE -- THERE'S
TWO WAYSES TO THINK ABOUT THIS,
ONE WHICH IS WE USE THESE TOOLS
TO ADDRESS A QUESTION THAT IS
OUT THERE.
SO EXAMPLE, THINGS SOME CIRCUIT
INVOLVED IN THIS ACCESS OF
BEHAVIOR AND THIS MAKES EASIER
TO ANSWER THOSE QUESTIONS.
THE HARDER QUESTION IS CAN WE
USE THIS TO GENERATE NEW
HYPOTHESES AND NEW TYPES OF
QUESTIONS AND THAT IS WHERE I
SEE MORE CHALLENGES.
>> MY TAKE IS THAT BOTH OF THOSE
ARE REALLY POSSIBLE.
AS BOTH SORT OF DISCOVERY TOOL
AND HYPOTHESIS GENERATE OR
TESTING TOOL AND HYPOTHESIS
GENERATING TOOL.
PART OF WHAT WE NEED AND PART OF
WHERE I THINK THE
COMPUTATIONALLISTS CAN HELP
EXPERIMENTALISTS IN THIS REGARD
IS FULLY UNDERSTAND THE SORTS OF
ASSUMPTIONS THAT GO INTO EACH
PARTICULAR METHOD.
FOR ANY MEASUREMENT TECHNIQUE
THERE ARE HUNDREDS OF
ASSUMPTIONS AND DECISIONS THAT
NEED TO BE MADE ON THE FRONT
END, SO IT IS IMPORTANT FOR
EXPERIMENTALISTS DEVELOPING THE
HYPOTHESES ARE USING THESE
METHODS TO DEVELOP HYPOTHESES TO
UNDERSTAND THAT LEADS THE BASIS
OF MANY OF THOSE ASSUMPTIONS,
AND THAT IS A PLACE WHERE MORE
COMMUNICATION, SOME OF THE MORE
CROSS TRAINING BING WAS TALKING
ABOUT, WHERE THAT CAN HAVE A
TREMENDOUS BENEFIT BECAUSE
OFTENTIMES WHAT SEEMS LIKE A
MINOR ASSUMPTION ON ONE END CAN
BE SUBSTANTIAL CONSTRAINT ON THE
OTHER.
THAT GOES IN BOTH DIRECTIONS.
>> ONE OF THE THINGS I LEARNED
THE HARD WAY SOMETHING THAT I
TRIED TO IGNORE SINCE MY
UNDERGRAD IN CLASSICAL MASS
WHICH IS WITH A LOT OF THESE NEW
APPROACH THAT WE ARE TAKING WE
REALLY HAVE TO START EDUCATING
PEOPLE MUCH MORE IN DYNAMICAL
SYSTEMS AND CONTROLLED THEORY.
IN METHODS THAT ACTUALLY ALLOW
US TO UNIQUELY ANALYZE THESE
TYPES OF DATA.
IT WAS A HARD FOR ME TO BRUSH
OFF THESE THINGS THAT I TRIED TO
IGNORE IN COLLEGE.
BUT I'M PAINFULLY GETTING BACK
TO THEM NOW BECAUSE THE TYPE OF
TRIAL STRUCTURE THAT WE ARE ALL
VERY FAMILIAR WITH AND THAT
SERVED US INCREDIBLY WELL IS
PROBABLY NOT THE RIGHT APPROACH
FOR THE FUTURE OF THE TYPES OF
DATA SETS THAT WE ARE CURRENTLY
GENERATING.
THIS WILL REQUIRE A SUBSTANTIAL
AMOUNT OF EFFORT ON THE SIDE OF
CLAN RATION BETWEEN
COMPUTATIONAL -- COLLABORATION
BETWEEN COMPUTATIONAL
NEUROSCIENTISTS AND EXPERIMENTAL
LISTS THAT CREATE DATA SETS RICH
ENOUGH TO TEST ASSUMPTIONS AND
METHODS AND SOME WILL BE MAYBE
REDUNDANT IN THE VERY BEGINNING,
BUT THEN WE CAN SLOWLY BUILD UP
ON THEM AND START TO UNCOVER A
NOVEL MECHANISMS AND I'M VERY
POSITIVE ABOUT IT.
JUST GOING TO TAKE A WHILE.
IT IS GOING TO BE DIFFICULT.
>> ADDING ON TO THAT, I THINK IN
TERMS OF THESE DATA SETS, WHEN
MACHINE LEARNING COMMUNITY
RECENTLY INTRODUCED BEST
PRACTICES FOR DOCUMENTING DATA
SETS SO DOCUMENTING IN A
STANDARDIZED WAY AND ALL THE
NECESSARY INFORMATION IS
INCLUDED FOR FUTURE USE,
SIMILARLY FOR MACHINE LEARNING
THERE WAS A CHECKLIST OR USING
BY NERVE (INAUDIBLE) IN
CONFERENCE THAT HELPS CHECK
PRODUCIBLE, WONDER IF SIMILAR TO
THESE BEST PRACTICES IF THERE
COULD BE INTRODUCED LIKE A
STANDARDIZE SET OF IS THINGS
USING TOOLS OR MODELS THAT
SHOULD BE INCLUDED THAT AFFECT
BEHAVIORAL UNDERSTANDING, THAT
SHOULD BE DOCUMENTED, AMONG --
GREAT TO LEARN MORE.
>> GREAT POINT.
>> ONE QUESTION THAT CAME UP IN
THE AUDIENCE Q&A AND SOMETHING
BING TALKED BRIEFLY BEFORE IS
ARE THERE BIO ETHICAL CONCERNS
ABOUT DEVELOPING THESE
TECHNOLOGY?
WHAT SHOULD WE DO ABOUT THAT?
IF YOU CAN TRACK SOMEONE LIKE
YOU HAVE BEEN SAYING AND DO
SOMETHING NEFARIOUS WITH THOSE
DATA, IS THAT CONCERN FOR US AS
DEVELOPERS OF THESE TOOLS THOUGH
THEY ARE IN ANIMALS?
>> I THINK THEY ARE.
>> GO AHEAD JAN.
>> NO, TIM, SORRY.
I WAS JUST GOING TO SAY I THINK
THAT THAT IS REALLY IMPORTANT TO
CONSIDER ESPECIALLY WHEN WE
START TO TALK ABOUT PREDICTING
BEHAVIOR AND ALSO PREDICTING
INTERNAL STATES BECAUSE A LOT OF
VANGS OF THESE METHODS ARE THEY
REVEAL THINGS THROUGH BEHAVIOR
THAT ARE SO SUBTLE THAT WE
HAVEN'T BEEN ABLE TO MEASURE
THEM BEFORE BUT THEY CORRESPOND
TO INTERNAL STATES THAT ANIMALS
ARE -- POTENTIALLY PEOPLE ARE
IN.
I THINK THAT THOSE ARE AREAS
WHERE WE NEED GUIDANCE FROM
BIOETHICISTS FOR SURE.
I THINK THE ANSWERS TO THOSE ARE
GOING TO BE SPECIFIC TO SPECIFIC
TECHNOLOGIES PERHAPS BUT I THINK
LAYING DOWN SOME CLEAR
GUIDELINES AS TO WHERE AREAS OF
CONCERNS ARE SO THAT AS
SCIENTISTS APPROACH THEM THEY
ARE NOT SO BLINDED BY THEIR
CREATIVITY AND EXCITEMENT OF
DISCOVERY THAT THEY BLAZE
THROUGH THEM.
>> JAN.
>> I WAS GOING TO SAY SOMETHING
VERY SIMILAR.
THE THING I WORRY ABOUT IS
ALREADY HAPPENING WHICH IS THERE
IS MASS SURVEILLANCE HAPPENING
IN THE WORLD, PEOPLE USING VIDEO
CAMERA SYSTEMS CB SYSTEMS,
ESPECIALLY IN SOME PARTS OF THE
WORLD AND THOSE CAN BE MISUSED
IN THE SAME TRUE FOR SOCIAL
MEDIA TRACKING, TRACKING OF OUR
BEHAVIOR ON PHONES, SO ON.
MY HOPE IS ALWAYS TYPES OF
ALGORITHMS THAT WE USE CAN BE
KEPT AS SPECIFIC AS POSSIBLE TO
OUR RESEARCH CASE.
THAT COULD HELP US TINY BIT.
WE HAVE TO BE VERY AWARE AS TIM
SAID THEY CAN BE MISUSED
ESPECIALLY INTO THE INFERENCE OF
INTERNAL STATES WHICH IS I THINK
WHAT A LOT OF US ARE WORKING ON.
>> SMALL THOUGHT ON TO THAT
WHICH IS WHEN THESE TECHNOLOGIES
A LOT OF TALK ABOUT TECHNOLOGIES
SO NOT ONLY USING AGENT BASED
MODELS, INTERFACING ANIMALS AN
HUMANS AND THERE THE QUESTIONS
AND WILL IS LIKE BASICALLY OPEN
PANDORA'S BOX ABOUT THESE IDEAS
ABOUT AGENCY AND FREE WILL AND
WHETHER OR NOT YOU ARE FEELING A
CERTAIN WAY BECAUSE IT IS YOU,
TIES IN TO THE WHOLE IDEA ABOUT
NEUROPHARMACOLOGY AND SO THERE
IS A LOT OF INTERESTING PROBLEMS
THAT ARE OPENED UP THERE.
IN A SPECIFIC INSTANCE OF
TRACKING OUR ABILITY TO DETECT
THESE STATES AS TIM GENTNER WAS
SAYING EARLIER, THE FACT THAT WE
CAN LOOK AT MICROEXPRESSIONS OR
TELLS OF THINGS THAT HAVE
PREVIOUSLY BEEN NOT EXTERNALLY
AVAILABLE TO US.
THAT REALLY MAKES PEOPLE THINK
ABOUT WHAT THEY ARE FREELY
GIVING AWAY WHEN WE WALK
OUTSIDE.
WE WILL PUT ON ZOOM CAMERAS.
>> ALL EXCELLENT POINTS.
THERE IS A QUESTION TOP LOADED
QUESTION, FROM AUDIENCE, WERE
THERE EPIC FAILURES IN TRACKING
CLASSIFICATION ANALYSIS THAT
WERE ILLUSTRATIVE AND HELP TO
IMPROVE APPROACHES METHODS AND
LEVELS?
>> MANY EPIC FAILURES, THE
NUMBER ONE EPIC FAILURE FROM MY
SIDE IS NOT PROPERLY TAKING INTO
CONSIDERATION THE ENVIRONMENT IN
WHICH ANIMALS ARE SUPPOSED TO
FORAGE, ARE SUPPOSED TO DO THEIR
TRACKING EXPERIMENTS AND TYPE OF
INFLUENCE THIS CONTEXTUAL
MODULATION HAS ON THE BEHAVIOR.
IT IS GREAT YOU CAN SET UP A
CAMERA SYSTEM THAT CAN HANDLE
TERABYTES AND TERABYTES PER HOUR
BUT THAT DOESN'T HELP IF THAT
SYSTEM CONSTRAINS OR INDUCES
BIAS IN THE BEHAVIOR THAT THE
ANIMAL SUPPOSED TO EXPRESS.
SO THINKING ABOUT THE
NATURALISTIC ASPECT ALSO IN
DESIGNING TYPES OF ENCLOSURES
AND SET UP THAT WE BUILD, IS
INCREDIBLY IMPORTANT AND I
CERTAINLY UNDERESTIMATED IT.
>> DID YOU START WITH YOUR
CAMERAS, JAN?
WAS THERE AN ISSUE YOU WERE MORE
MODEST WITH YOUR HARDWARE AND
THERE WAS EPIC FAILURE SO THEN
YOU SCALED UP?
>> YES.
THAT IS ANOTHER PROBLEM WE
INITIALLY ENCOUNTERED.
WE WENT THROUGH MANY ITERATIONS
WITH WHAT IS THE RIGHT OVERLAP,
HOW CAN WE COMPUTATIONALLY COME
UP WITH A MODEL THAT CAN TELL US
SOMETHING HOW ACCURACY SCALES.
IN THE END WE CAME UP WITH A
VERY SIMPLE ANALOGY, THE MORE
THE LESS YOU HAVE OCCLUSIONS IN
YOUR ACTUAL DATA SET, MORE
CONSENSUS YOU CAN BUILD THE
BETTER YOU WILL PERFORM.
IT IS A RUE YESIALITY BUT
REALIZATION WE HAVE TO MAKE.
>> I WOULDN'T SAY THIS IS AN
EPIC PAIL BUT ONE OF THE
CHALLENGES WE DEAL WITH IS THOSE
ISSUES IN MISSING DATA OR
MISIDENTIFIED PICK, 98% OF DATA
IS BEAUTIFUL AND CLEAN, LAST ONE
OR TWO IS EITHER NOISY, WRONG OR
-- AND WHAT CAN WE DO WITH THAT,
SYSTEMATIC BIASES IF YOU ARE
MISSING ONE STATE ONE ACTION SO
I WOULD SAY A LOT OF PEOPLE IN
THE LAB END UP LIKE ALL DATA
SCIENCE DEALING WITH MISSING
DATA PROBLEM IS A CHALLENGE.
ANYTHING DONE ON THE FRONT END
IS HUGE.
>> I GUESS I WILL ADD SOMETHING.
IN ADDITION TO THAT ONE OF THE
OTHER CHALLENGES I SEE IS
APPLYING MODELS ACROSS LABS,
EVEN LABS THAT HAVE SAME
ORGANIZATION OR SIMILAR
SETTINGS.
YOU THINK DATA IS SIMILAR BUT
DISTRIBUTION LIKE IN THE LANE OR
ARENA SIDES ANIMAL CHANGES IN A
WAY MODELS CAN BE APPLIED
DIRECTLY WITHOUT RETURNING AND
THE SLIDE TO RETRAIN SOMETIMES
BUT TAKES MORE EFFORT SO IT IS
TO OPEN QUESTION, FOR THE
DEVELOP A MODEL THAT GENERALIZES
ACROSS LABS FOR SAME ORGANISMS
AND SIMILAR SET UP.
OR EVEN ACROSS THE SAME LAB JUST
ACROSS THE HALL WEI.
>>
>> ANOTHER QUESTION.
GREAT WORK ALL.
THE CURRENT STATE OF BEHAVIORAL
QUANTIFICATION BORROWS CURRENTLY
EXISTING METHOD MACHINE
LEARNING/MACHINE VISION.
ARE NOVEL APPROACH, PRESUMABLY
SPECIFIC TO OUR CONTEXT, ARE
THOSE NECESSARY?
SOMETHING THAT MOVES BEYOND
STATE OF COMPUTER VISION, SO
WHAT KIND OF NEUROSPECIFIC
INNOVATION DO WE POTENTIALLY --
>> FOR US THE QUESTION IS HOW DO
YOU GET LONG TERM STABLE
RECORDINGS IN ANIMAL EXTREMELY
STRONG AND WHOSE VELOCITY IS
SERIOUSLY OPPOSED TO STABLE
RECORDINGS AND THE BRAIN
PULSATING AROUND.
OUR SOLUTION TO THAT HAS BEEN
FLEXIBLE ELECTRONICS AND
FLEXIBLE APPROACH AND IT WORKS
FAIRLY WELL.
BUT I THINK THERE IS A LOT MORE
TO BE DONE THAT IS VERY SPECIES
SPECIFIC.
>> I WILL ADD ON THAT MOSTLY
WORK IN COMPUTER VISION
CONFERENCES SO I DO FEEL LIKE
THERE WAS A COMPUTER VISION
CONTRIBUTION AND IN MY OPINION
THE KEY CONTRIBUTIONS ARE THAT
THEY LEVERAGE UNIQUE ASSUMPTIONS
MAKING BEHAVIOR VIDEOS FOR
EXAMPLE DISCOVERY PAPER WE HAVE
SEEN BACKGROUND (INAUDIBLE) ALL
VIDEOS BUT LARGELY TRUE IN
BEHAVIORAL VIDEOS IN THIS
SETTING N. THE TEST PROGRAM WE
LEVERAGE HUMAN DOMAIN KNOWLEDGE
THAT WAS KIND OF UNIQUE FROM MY
COLLABORATORS IN BEHAVIORAL
NEUROSCIENCE, SO I DO THINK
THERE ARE THINGS IN THE -- THAT
CAN BE TOO MACHINE LEARNING
COMPUTER CONTRIBUTIONS THAT DO
GENERALIZE BUT WE JUST HAVE TO
LIKE THINK ABOUT THEM CAREFULLY.
>> ONE THING THAT I HAVE BEEN
REALLY EXCITED ABOUT IS ADDING
ON NOT JUST COMPUTER VISION
ASPECT OF IT THAT WE HAVE
OFFERED IN MACHINE LEARNING
COMPUTER VISION BUT THERE IS
UNIQUE ASPECT OF BIOLOGICAL DATA
THAT IS VERY, VERY HIGH
MODALITY.
IT IS NOT COMPUTER VISION, IT IS
SMELL DATA AND YOU MAY HAVE LIKE
CORTISOL LEVELS OR EKGs OR
EMGs, ALL KIND OF THINGS.
THE TYPES OF QUALITY DIFFERENT
DATA WE CAN GET MONITOR THE SAME
ORGANISM, SAME SET OF ORGANISMS
AT SAME TIME IS BIG AND IT
VERSUSLY EXCEEDS WHAT IS
TYPICALLY TREATED IN WHAT YOU
SEE IN MACHINE LEARNING
CONFERENCES SO THAT IS A NEW
CHALLENGE FOR ANIMAL BEHAVIOR.
>> I WOULD ECHO JENNIFER'S
EARLIER POINT ABOUT DOMAIN
KNOWLEDGE, WE HAD 27, 28 DATA
SETS FROM ANIMALS INCLUDING
HUMANS.
THEY ARE ALL PUNITIVELY
VOCALIZING IN VERY SIMILAR WAYS
AND ONE OF THE THINGS WE FOUND
WAS THAT APPLYING UNSUPERVISED
METHODS IS REVEALING BUT IF
LAYERED OVER THE TOP OF DOMAIN
SPECIFIC KNOWLEDGE THEN THE
DEPTH OF THE INFORMATION THAT
CAN BE GAINED IS OFTEN
MULTIPLICATIVELY INCREASED AND
SO IN INSTANCES WHERE NO DOMAIN
KNOWLEDGE EXISTS, UNSUPERVISED
METHODS WHETHER BORROWED FROM
COMPUTER VISION OR NOT CAN BE
REVEALING BUT IF YOU CAN COMBINE
IT WITH DOMAIN KNOWLEDGE THEN
YOU ARE IN A MUCH MORE
ADVANTAGEOUS POSITION AND
BECAUSE IT IS OFTENTIMES HARD TO
KNOW WHAT GROUND TRUTH IS.
AND IF YOU ARE JUST BORROWING A
METHOD FROM FROM ANOTHER FIELD,
WHERE ASSUMPTIONS ARE VALID YOU
ARE OFTENTIMES YOU ARE LEFT TO
SCRATCH YOUR HEAD.
YOU HAVE A HYPOTHESIS TO TEST
BUT MAYBE THAT IS A LONG WAY
FROM WHAT YOU WANT TO FIND.
>>
>> ANOTHER WAY BEYOND COMPUTER
VISION.
WHAT WE WANT TO DO IS RELATE TO
WHAT IS GOING ON IN THE BRAIN.
THE COMPUTER VISION IMAGE
ANALYSIS IS THE GOAL ITSELF.
BUT WE WANT TO RELATE THIS TO
NEURAL ACTIVITY OR SOMETHING
ELSE IN THE BRAIN SO IF THERE IS
WAYS TO DO THAT END TO END
INSTEAD OF THINKING IMAGE
PROCESSING AND THEN NEURAL DATA
ANALYSIS PROBLEM THAT CAN BE
POWERFUL.
>> THERE IS ONE LAST PART THAT
DIDN'T GET DISCUSSED YET THAT WE
KIND OF HAVE LOT OF TROUBLE WITH
AND PUTTING EFFORT IN THAT IS
VARIABILITY BETWEEN ANIMALS THAT
YOU ARE MEASURING.
FOR EXAMPLE MEASURING FIVE MICE
MUCH MORE SIMILAR TO EACH OTHER
THAN FOR EXAMPLE FIVE MONKEYS OR
HUMANS OR -- I'M JUST PANELING
HERE AND I DON'T KNOW FIVE
ZEBRAFISH.
SO TRYING TO COME UP WITH A
MODELING FRAMEWORK THAT MODELS
EFFECT OF MANIPULATION OR
CERTAIN STATES, AS WELL AS
INTERINDIVIDUAL VARIABILITY IS
INCREDIBLY IMPORTANT TO MAKE
SENSE OF THE DATA SETS THAT WE
ARE TRYING TO GENERATE.
>> SO THERE IS A SESSION TIMER
ON MY SCREEN THAT COUNTED DOWN
TO ZERO A FEW MINUTES AGO.
WE STILL HAVE TIME?
>> I WISH I COULD TELL YOU.
>> WE WILL KEEP GOING.
>> SO WE DO HAVE TO WRAP UP, I
WOULD LIKE TO THANK EVERYONE FOR
ATTENDING AND ALSO FOR
PARTICIPATING IN THE PANEL.
I THINK THIS WAS A WONDERFUL
EXPERIENCE AND I HOPE
ILLUMINATING FOR EVERYONE
INVOLVED AND THIS IS VERY
EXCITING FIELD OF RESEARCH AND
HOPE WE CONTINUE TO HAVE THESE
GROUP DISCUSSIONS.