>> GOOD MORNING, EVERYONE.
MY NAME IS ANDREW BREEDAN A
PROGRAM OFFICER AT THE NATIONAL
INSTITUTE OF MENTAL HEALTH AND
MEMBER OF THE WORKSHOP PLANNING
TEAM.
ON BEHALF OF THE ENTIRE TEAM I'M
PLEASED TO WELCOME YOU TO THE
SECOND DAY OF THE BRAIN
INITIATIVE WORKSHOP ON
OPPORTUNITIES AND CHALLENGES FOR
COORDINATED EFFORTS TO ADVANCE
HUMAN NEUROSCIENCE WITH
STIMULATION AND RECORDING
APPROACHES.
SO FOR THOSE WHO MAY BE JUST
JOINING US TODAY AS YOU CAN SEE
IN OUR AGENDA, YESTERDAY OUR
PANELISTS HAD GREAT HIGH-LEVEL
DISCUSSION ORGANIZED AROUND
THREE KEY THEMES.
FIRST, WHAT TYPES OF
PERTURBATION ARE VALUABLE FOR
EXPLAINING COGNITION AND
BEHAVIOR AND KEY CONSIDERATIONS
FOR THE USE OF BEHAVIORAL
ASSESSMENTS AND PERTURBATION
RECORDING INSTRUMENTS AND WHAT
LEVELS OF UNDERSTANDING CAN WE
GAIN USING THESE APPROACHES.
I WANT TO FIRST THANK OUR
PANELISTS FOR EXTREMELY
INSIGHTFUL DISCUSSIONS AND LATER
IN THE DAY WE'LL HAVE A MORE
EXTENSIVE RECAP OF THE KEY
THEMES DISCUSSED IN THE SESSIONS
BUT THIS WILL HAPPEN DIRECTLY
ABOUT OUR FINAL SESSION FOCUSSED
ON PRACTICAL QUESTIONS IN ORDER
TO SET THE STAGE FOR THIS
DISCUSSION.
SO YOU CAN SEE ON THE AGENDA THE
THEME OF THE SESSION WILL BE HOW
THEORY AND MODELLING CAN BE
INTEGRATED WITH PERTURBATION TO
UNDERSTANDED OBSERVED BEHAVIOR
AND THIS WILL BE CHAIRED BY
DR. BUTSON AND CLAYTON AND WE'LL
HAVE A RECAP OF THE MEETING
FOLLOWING THAT AND THEN
TRANSITION TO SESSION 5 AND 6.
THESE SESSIONS WILL CONSISTENT
OF MORE IN DEPTH PANEL
DISCUSSIONS OF THE PRACTICAL
QUESTIONS NEEDED TO INFORM
COORDINATED STIMULATION
RECORDING EFFORTS IN HUMANS.
SESSION 5 WILL BE CHAIRED BY
DOCTORS MICHAEL FOX AND
FRANKOWSKI AND SESSION 6 CHAIRED
BY DR. QUINLAN AND WE WANT TO
PROMOTE DISCUSSION AMONG
PANELISTS AND LIKE YESTERDAY
HOPE TO HEAR A RANGE OF
DISCUSSIONS.
WHILE CONVERGENCE COULD BE A
BONUS IT'S NOT NECESSARY IN
HEARING A DIVERSITY OF OPINIONS
COULD BE REALLY USEFUL AS WELL.
AND WE'RE ALSO REALLY INTERESTED
TO HEAR FROM OUR ATTENDEES TOO.
THOSE JOINING ONLINE LISTENING
TO THE WORKSHOP TODAY WE'D
WELCOME YOUR INPUT AND TO DO SO
WE HAVE A REQUEST FOR
INFORMATION THAT'S ACTIVE YOU
CAN SEE HERE.
YOU CAN USE THIS TO PROVIDE
THEMES OF THE WORKSHOP AND
QUESTIONS AND RELATED MATTERS
AND YOU CAN USE THIS QR CODE OR
LEARNING TO GO TO THE R 5 TO
PROVIDE YOUR E-MAIL AND MULTIPLE
RESPONSES ARE ALLOWED.
IF YOU'RE LISTENING TO ONE
SESSION AND HAVE A SPECIFIC
THOUGHT AND THEN YOU'RE
LISTENING TO A LATER SESSION
THROUGHOUT THE WORKSHOP YOU CAN
SEND MULTIPLE RESPONSES AND THAT
IS CERTAINLY ALLOWED AND
WELCOME.
SO NOW THAT WE'VE ADDRESSED SOME
GENERAL HOUSEKEEPING ITEMS I'LL
TURN IT OVER TO OUR SESSION 4
CHAIRS, DR. CHRIS BUTSON FROM
UNIVERSITY OF FLORIDA AND
DR. BINGHAM FROM NINDS AND OUR
SESSION 4 PANELISTS.
JOIN US IN WELCOMING YOU ARE
CHAIRS AND PANELISTS.
>> THANK YOU.
I'M GOING TO GO AHEAD AND SHARE
SLIDES.
ONE SECOND.
>> CAN YOU SEE THAT OKAY?
>> WE'RE SEEING THE PRESENTER
VIEW.
COULD YOU HIT THE SWAP
DISCOVERIES BUTTON AT THE TOP.
HIT USE SLIDE SHOW.
>> YEP.
>> SO I JUST WANT TO EXPRESS A
THANK YOU TO THE ORGANIZERS AND
MY FELLOW SPEAKERS AND
DISCUSSANTS ON THE PANEL FOR
JOINING TODAY.
I KNOW GETTING THIS WORKSHOP
TOGETHER WAS A TREMENDOUS AMOUNT
OF WORK OVER A LONG PERIOD OF
TIME AND ONE OF THE THINGS
INVOLVED WITH THAT WORK AMONG
OTHER PROGRAM STAFF WAS TAKING
RICH AND ABSTRACT IDEAS AND
ORGANIZING THEM IN A WAY THAT IS
LOGICAL AND REALLY FACILITATES
IN DEPTH DISCUSSION.
I THINK IN ACADEMIA AND SCIENCE
WE'RE USED TO WORKING WITH
ABSTRACT IDEAS BUT THE TOPIC OF
THEORY AND MODELLING OFTEN ADDS
A WHOLE OTHER LAYER OF
ABSTRACTION.
FOR THEORY AND MODELLING,
MATHEMATICS IS ITS NATIVE
LANGUAGE.
THIS IS BECAUSE IT CAN CONCISELY
DESCRIBED DATA AND SYSTEMS AND
IN THE PRACTICE OF MODELLING
WE'LL TAKE THE MATHEMATICAL
MODELLING AND CODIFY THEM TO
PYTHON AND JULIA AND USE
ADDITIONAL SPECIALIZED LANGUAGES
AND THESE ARE MORE FAMILIAR TO
SOME THAN OTHERS.
PERHAPS BECAUSE OF THAT AND
BECAUSE PEOPLE USE THESE
TECHNIQUES ARE FAMILIAR WITH THE
LANGUAGES IT'S EASY TO VEER OFF
COURSE INTO REALLY ESOTERIC
IDEAS AND CONCEPTS.
I THOUGHT IT MIGHT BE USEFUL TO
BRIEFLY DESCRIBE THE MODELLING
PROCESS OF TAKING THEORY AND
DATA AND TURNING IT INTO
SOMETHING USEFUL AND PREDICTIVE.
SO THE WAY THAT I DESCRIBE THIS
PROCESS IS REALLY CREATING A NEW
SPECIES OF WILD ANIMAL THAT HAS
NEVER BEEN SEEN BEFORE AND THAT
HAS TAB TAMED TO BE USEFUL AND
CAN TAKE A 100 TIMES LONGER AND
INVOLVES THIS INVOLVES A PROCESS
OF HOW DO I MAKE IT STABLE AND
MAKE IT UNDERSTANDABLE AND LEARN
ITS BEHAVIOR AND TRAIN IT.
IN THE END WE HAVE TO PASS A
LITMUS TEST AND SENSITIVE TO
INITIAL CONDITIONS.
THIS PROCESS CAN BE VERY
INSTRUCTIVE BECAUSE IT CAN
IDENTIFY PARAMETERS AND LATENT
VARIABLES THEY MIGHT NOT HAVE
BEEN OBVIOUS AT THE OUTSET.
I'M SORRY, I SKIPPED OVER
SOMETHING IN THE BEGINNING.
I'M JUST GOING TO TOUCH ON THAT
NOW.
I PUT THIS SLIDE TOGETHER JUST
TO EXPRESS GRATITUDE FOR THE
BRAIN INITIATIVE AND I JUST WANT
TO HIGHLIGHT THE FACT THAT AS A
RESULT OF THE BRAIN INITIATIVE
WE WERE ABLE TO, I ALONG WITH
MANY COLLABORATORS IN MULTIPLE
INSTITUTIONS IN THESE STUDIES,
WERE ABLE TO PROSPECTIVELY TEST
NEW THERAPIES IN HUMANS IN WAYS
THAT PROBABLY WOULD NOT HAVE
BEEN POSSIBLE WITHOUT THE BRAIN
INITIATIVE.
ONE OF THESE STUDIES IS NOW
COMPLETE AND PUBLISHED IN
DECEMBER AND THREE MORE ARE
STILL ONGOING.
SO ALL OF THESE STUDIES LISTED
WITH THE EXCEPTION OF ONE OF
THEM IS GEARED TOWARDS
DEVELOPING NEW THERAPIES FOR
PATIENTS WITH INTRACTABLE
NEUROLOGICAL OR PSYCHIATRIC
CONDITIONS.
SO THIS IS REALLY ENABLED US TO
KIND OF CHANGE WHAT WE CAN DO
AND THE WAY THAT WE'RE THINKING
ABOUT THESE PATIENT POPULATIONS.
SORE ROY ABOUT SKIPPING THAT IN
THE BEGINNING.
THE PROCESS OF LEARNING HOW THE
MODEL BEHAVES AND WHAT IT'S
SENSITIVE TO CAN BE REALLY
INSTRUCTIVE.
YOU CAN IDENTIFY PARAMETERS AND
LATENT VARIABLES THAT MIGHT NOT
HAVE BEEN OBVIOUS AND GO THROUGH
THE PROCESS OF UNDERSTANDING,
OKAY, WHAT DO WE DO WITH THESE
VARIABLES.
SOMETIMES THOSE INCLUDE
VARIABLES WE CAN MEASURE
PHYSIOLOGICALLY.
WHEN YOU FIND THOSE YOU GET THE
FEELING YOU'RE POTENTIALLY ON TO
SOMETHING.
THEN YOU GO THROUGH THE PROCESS
OF ASKING IS THIS MODEL
SUFFICIENTLY PRECISE AND
ACCURATE FOR THE EXPERIMENTS
WE'RE CONDUCTING.
AND MODELS ARE TIGHTLY
INTEGRATED INTO BEHAVIORAL
STUDIES, PHYSIOLOGICAL STUDIES,
PERTURBATION STUDIES, INVASIVE
OR NON-INVASIVE.
THIS PROCESS OF WEAVING IN THE
MODELLING INTO THE REST OF THE
STUDIES CAN TAKE WEEKS OR EVEN
MONTHS TO PLAN THOSE
EXPERIMENTS.
THIS IS REALLY A PAINSTAKING
PROCESS.
THEN WE'LL ASK QUESTIONS ABOUT
CAN THIS MODEL BE VALIDATED?
BUT IN THE END WE ASK CAN THIS
BE USED TO MAKE TESTABLE
PREDICTIONS?
AND IF WE BELIEVE THE ANSWER IS
YES, THEN WE START DESIGNING
EXPERIMENTS THAT CAN TEST THOSE
IDEAS AND TEST THOSE
PREDICTIONS.
ONCE WE GET TO THAT POINT, THEN
WE HAVE TO START THINKING ABOUT
SCIENTIFIC VISUALIZATION.
THIS IS A PROCESS THAT CAN
REALLY TAKE AN INCREDIBLE AMOUNT
OF TIME AND EFFORT ON ITS OWN.
AND TRYING TO CONCISELY DESCRIBE
SOMETIMES VERY LARGE AND COMPLEX
DATA SETS IN WAYS THAT ARE
UNDERSTANDABLE FOR DISSEMINATION
AND ALSO IN WAYS THAT ARE
UNDERSTANDABLE FOR FOR EXAMPLE
CLINICAL DECISION SUPPORT OR
UNDERSTANDING IN A POTENTIALLY
NOVEL THERAPY HOW IT SHOULD BE
APPLIED IN INDIVIDUALS.
IN THE END THE LITMUS TEST FOR
THIS PROCESS IS ASKING IS IT
UNDERSTANDABLE AND IMPORTANTLY
DO THE VISUALIZATIONS CREATE NEW
INSIGHTS WE DIDN'T HAVE BEFORE?
IF YOU GET THROUGH ALL THAT
YOU'RE NEARING THE END OF THE
PROCESS AND GET THE VERY
GRATIFYING FEELING OF PUTTING A
NEW TOOL IN YOUR TOOLBOX.
MORE IMPORTANTLY, YOU HAVE
SOMETHING THAT HOPEFULLY CAN BE
INTEGRATED INTO THE REPERTOIRE
OF SCIENTIFIC TOOLS TO ASK
QUESTIONS AND TEST NEW
HYPOTHESES.
SO I JUST PUT TOGETHER THIS
BRIEF INTRODUCTION BECAUSE I
WANTED TO GIVE AN OVERVIEW OF
WHAT I CONSIDER TO BE THE
EXPERIMENTAL SCIENCE OF
MODELLING AND I HOPE WE CAN USE
IT AS A CONSTRUCT FOR
DISCUSSION.
AS AN EXAMPLE OF THIS PROCESS I
WANT TO POINT OUT THIS REVIEW
PAPER PUBLISHED FROM THREE WELL
KNOWN NEURO SCIENTISTS.
AS A REVIEW PAPER IT'S NOT
TRYING TO SHOW RESULTS.
IT'S TRYING TO EXPRESS IDEAS.
I LOVE THIS FIGURE ESPECIALLY
PART D ON THE RIGHT-HAND SIDE.
IN THE PAPER THEY DON'T TALK
ABOUT WHAT DATA WAS COLLECTED
PHYSIOLOGICALLY OR WHAT WAS THE
MODELLING THOUGH MODELLING HAD
TO BE USED, THEY BEAUTIFULLY
WOVE EVERYTHING TOGETHER TO A
SINGLE UNIFYING PRESENTATION
THAT EXPRESSES HOW INTRACELLULAR
AND EXTRA CELLULAR ACTIVITY
EVOLVED IN TIME AND SPACE.
IN THIS CASE FOR AN INDIVIDUAL
NEURON.
SO I USE THIS IN TEACHING AND
USE THIS AS AN EXAMPLE OF KIND
OF THE CULMINATION OF THIS
PROCESS.
I'LL WRAP UP THERE.
I WANT TO SAY I ENJOYED THE
SESSION YESTERDAY AND NOTED A
FEW THEMES WE MIGHT INCLUDE IN
THE DISCUSSION TODAY INCLUDING
MECHANISMS, WHERE AND HOW ENERGY
IS DELIVERED DURING PERTURBATION
AND QUANTITATIVE COMPARISONS
AMONG DIFFERENT STIMULATION
MODALALITIY -- MODALITIES I'M
PLEASED TO BE JOINED BY
DR. RITTER, DR. KUCEYESKI AND
DR. SHINE AND DR. PETRACHEF AND
DR. SHANECHI.
>> I'M SHARE MY SCREEN.
I WANT TO SHARE THE LATEST
DEVELOPMENTS AND BRING THAT WORK
MODELLING AND WHAT WE'RE DOING
WE RECONSTRUCT INDIVIDUAL BRANDS
OF ANIMALS OR HUMANS AND THIS
GIVES US A GREAT OPPORTUNITY TO
UNDERSTAND HOW DIFFERENT
ENTITIES ARE GENERATING TO ARE
OBSERVATIONS AND THE FRAMEWORK
WE'RE USING HAS BEEN DEVELOPED
SOME TIME AGAIN AND WE WORKED
WITH OTHERS COORDINATING THE
INITIATIVE THAT WAS FIRST
AVAILABLE IN 2013 I THINK OR
2012 EVEN AS A SOFTWARE AND NOW
IT'S GETTING FURTHER ADVANCED.
NOTICE WE HAVE MIGHTY SPEAR
MODELS AND THERE'S OTHER
COMPONENTS OF THE BRAIN ARE
SIMULATED AS CAUSAL RESOLUTION
AND ALL KINDS OF NEURONAL
ACTIVITY AS A RESULT OF COMPLEX
INTERACTIONS OF DIFFERENT
ELEMENTS IN THE BRAIN THAT ARE
INFORMED BY THE DATA THE IMAGING
DATA OF THE INDIVIDUAL SUBJECTS.
TO GIVE YOU TWO QUICK EXAMPLES
OF RECENT WORK WHERE WE
UNDERSTOOD PRINCIPLES OF HOW THE
BRAIN DYNAMICS EVOLVED.
WE UNDERSTOOD THE MECHANISM OF
GENERATING THESE TRAVELLING
WAVES FRONTS THAT TRAVEL OVER
THE BRAIN GLOBALLY AND CAN BE
ALSO FOUND ON ALL KIND OF
SPATIAL SCALES AND THE POTENTIAL
SUCH WAVE FORMS HAVE
SYNCHRONIZING POTENTIAL AND
BUILDING PLASTICITY AROUND CAN
BE SIMULATED WITH RULES AND THE
SIMULATION.
ANOTHER EXAMPLE WHERE WE'VE
LINKED THE DYNAMICS SIMULATED TO
THE BEHAVIOR AND THERE'S A
RECENT STUDY WHERE WE USE THE
HUMAN CONNECTOME DATA ACTUALLY
TO BUILD 50 SUCH VIRTUAL BRAINS
AND PLUCKED CIRCUIT MODELS IN
THE FRONTAL PARIETAL CORTEX
INDEPENDENT OF THE GLOBAL
ACTIVITY OF THE INDIVIDUAL'S
BRAINS.
AND VALUABLE TO PREDICT THE
PERFORM OF THESE INDIVIDUALS
ALSO MEASURED FINDING THEORY HOW
THE DIFFERENCES CAN BE EXPLAINED
AND THE SPEED OF STIGS MAKE --
DECISION MAKING AND THE FINAL
GOAL IS TO BRING INNOVATIONS TO
THE CLINIC TO MAKE THE PATIENTS
BENEFIT AND DEVELOPING MODELS
FOR DEEP BRAIN STIMULATION AND
WITH OTHERS WHAT YOU SEE IS NICE
POTENTIAL DATA INTEGRATION.
WE HAVE THE DATA OF A PATIENT
BUT ALSO DETAILED DATA AND THE
ADDITIONAL DEGREE OF DETAIL CAN
BE INCLUDED BECAUSE OF OUR
PATIENT SPECIFIC BRAIN FOLLOWS
SPECIFIC STANDARDS AND USES THE
STANDARDS TO INTEGRATE THE
INFORMATION AND BUILD MODELS AND
THE BASIC UNDER LAYER OF FINE
DEGREE OF DETAIL TO UNDERSTAND
THE IMPACT OF DEEP BRAIN
STIMULATION OR THE DYNAMICS AND
THE LOCAL NETWORK AROUND THE
THALAMUS AND GLOBALLY AROUND THE
REST OF BRAIN.
THE FINAL SLIDE IS ABOUT TESTING
TRUSTWORTHINESS BEFORE GOING TO
THE PATIENT AND NEED TO BE
VALIDATED AND CERTIFIED AND
DEVICE REGULATION AND THE FIRST
OF LEGAL FRAMEWORK FOR A.I. AND
WE HAVE THE TESTING FACILITY TO
DEFINE STANDARDS AND TO ENSURE
THAT SUCH COMPLEX APPLICATIONS
THAT RELY ON MATHEMATICS AND ARE
ALSO CONTEXT DEPENDENT, SO
CHANGE OF INPUT CAN CHANGE THE
BEHAVIOR THAT THEY CAN BE
ASSESSED FOR RISK DEPENDING ON
THE APPLICATION AND PATIENTS.
I HOPE I WAS ABLE TO SHOW YOU
THE POTENTIAL I SEE IN THE BRAIN
MODELLING AND THANK YOU VERY
MUCH FOR THE OPPORTUNITY TO
DISCUSS THIS AND LOOKING FORWARD
TO THE OTHER PRESENTATION AND
DISCUSSION.
THANK YOU.
>> THANKS SO MUCH.
IT'S A MAJOR UNDERTAKING
CROSSING A LOT OF DOMAINS
INCLUDING REGULATORY.
NEXT WE'LL TURN IT OVER TO OUR
NEXT SPEAKER, DR. KUCEYESKI.
>> OKAY, SHARE MY SCREEN.
>> SO YEAH, FIRST I WANT TO SAY
THANK YOU FOR INVITING ME.
IT'S A PLEASURE TO BE HERE.
ESPECIALLY TO CHRIS AND CLAYTON
FOR INVITING US AND PUTTING
TOGETHER THIS FANTASTIC PANEL.
AND I JUST WANT TO SAY THAT
DR. RITTER'S PRESENTATION THERE
WAS BEAUTIFUL AND IT'S A GOOD
INTRODUCTION TO MINE BUT SO NAME
IS AMY KUCEYESKI FROM CORNELL
MEDICINE A PROFESSOR IN THE
RADIOLOGY DEPARTMENT AND BRAIN
AND MIND INSTITUTE AND WORK IN
BRAIN BEHAVIOR MAPPING USING
DIFFERENT COMPUTATIONAL
APPROACHES AND A.I. AS WELL.
IT'S A PERFECT INTRODUCTION.
THIS IDEA OF THE BRAIN IN A BOX
OR DIGITAL TWIN IS A WAY OF
INTEGRATING DIFFERENT SOURCES OF
INFORMATION ABOUT A PARTICULAR
PERSON TO SORT OF MAKE A
COMPUTATIONAL MODEL THAT IS IN A
VIRTUAL ENVIRONMENT WHICH YOU
CAN THEN PROBE TO SORT OF SEE
WHAT HAPPENS TO THE BRAIN IF YOU
APPLY DIFFERENT MODEL OF THE
STIMULATION AND FREQUENCY AND
DURATION OF THE STIMULATION AND
TAKES INTO ACCOUNT THE PERSON'S
ANATOMY AND PHYSIOLOGY AND MRI
AND AS WELL AS THEIR ANATOMICAL
CORTICAL FOLDING AND ALSO TOOK
INTO ACCOUNT TE BRAIN STATES AND
RECORDING STIMULATION INCLUDING
THINGS OVER ALL AROUSAL OR THE
PERSON'S ACTIVITY PATTERN AT THE
POINT OF STIMULATION DELIVERY.
AND THEN OF COURSE THERE'S BRAIN
BEHAVIOR MODELS.
I WORK A LOT IN THIS USING A.I.
OR STATISTICAL APPROACHES TO MAP
BRAIN ACTIVITY OR FUNCTIONAL
ACTIVITY TO BEHAVIOR.
IF WE HAVE THIS END TO END TWIN
OF A PERSON WE CAN FIND
PARAMETERS TO GET A PARTICULAR
BEHAVIORAL OUTCOME.
WE COULD ALSO SKIP -- THIS MAY
BE A CONTROVERSIAL STATEMENT FOR
THE PANEL BUT SKIP THE BIO
PHYSICAL MODEL AND TAKE IN
INFORMATION ABOUT THE PARADIGM
AND PREDICT THE OUTCOME
ALTOGETHER.
SOME OF THE APPROACHES ARE
NETWORK CONTROL THEORY TO MODEL
ACTIVATION.
THIS PRINCIPLE IS A CONNECTED
DYNAMICAL SYSTEM THAT CAN BE
CONTROLLED.
SO IN THIS CASE THE COMPLEX
SYSTEM IS THE BRAIN AND HAS THE
DIFFERENT STATES OF ACTIVATION
AND WHEN I SAY STATE I MEAN
PATTERN OF BRAIN ACTIVITY AT
THAT TIME AND MOVE THROUGH THE
STATES WITH SOME LEVEL OF
REGULAR PROBABILITIES.
THIS WAS FIRST INTRODUCED BY
DANNY'S LAB AND GLAD TO HEAR
FROM THEM YESTERDAY AND A WAY TO
INTEGRATE THE STRUCTURAL
CONNECTOME WITH THE FUNCTIONAL
PATTERNS OVER TIME USING A
SYSTEM OF DIFFERENTIAL
EQUATIONS, I WON'T GO INTO
DETAIL BUT A WAY OF PREDICTING
BRAIN ACTIVITY FROM CURRENT
STATE.
WE APPLIED THIS IN MANY
DIFFERENT CASES.
WE'VE SEEN NETWORK CONTROL
THEORY BASED NETWORKS CALLED
TRANSITION ENERGY THE AMOUNT OF
ENERGY YOU NEED TO INJECT IN THE
SYSTEM TO COMPLETE STATE
TRANSITIONS AND SEE THE
TRANSITION ENERGY IS DECREASED
IN PSYCHEDELICS AND INFECTIOUSED
IN PEOPLE WITH HEAVY ALCOHOL USE
AND INCREASED IN MILD TBI AND
DECREASED AND INCREASED ACROSS
DISABILITY AND PEOPLE WITH
MULTIPLE SCLEROSIS.
I'LL TALK ABOUT A CASE STUDY THE
MOST STRAIGHTFORWARD STUDY WITH
DATA FROM PEOPLE WHO HAD AN LSD
SESSION AND ANOTHER DATA WITH
OTHERS SUBSTANCES AND IT COULD
BE RELATED TO TRANSITION ENERGY
NEEDED TO COMPLETE STATE
ADMINISTRATIONS.
WE SET OUT TO TEST IT AFFECTED
THE FRAMEWORK AND FOUND IT AND
YOU SEE THE TIME TRANSITION
ENERGY AND AFTER THE PSILOCYBIN
INFUSION WE SEE A GREAT DECREASE
THAT REMAINS CONSISTENT ACROSS
THE INFUSION.
WE ALSO WANTED TO TEST ON
INDIVIDUAL SUBJECT LEVEL IF THE
AMOUNT OF DECREASED ENERGY WAS
RELATED TO INCREASES IN ENTROPY
AND SEE THIS IS TRUE OR
CORRELATIONS ACROSS THE METRICS
BETWEEN SUBJECTS AND
INDEPENDENTLY VALIDATED IN
ANOTHER DATA SET WHERE THEY DID
PLASMA SAMPLING OF THE SINNOSIN
LEVEL AND FOUND CORRELATED WITH
THE ENTROPY OF THE BRAIN
ACTIVATION.
MECHANISTICALLY WE KNOW
PSILOCYBIN AND LSB ACT ON THE
SEROTONIN RECEPTORS AND HAD PET
DATA WHERE WE HAD SEROTONIN
CONCENTRATION MAPS AND
INTEGRATED THAT IN OUR FRAMEWORK
TO SEE WHAT IT WOULD DO TO THE
CONTROL ENERGIES IN THE VIRTUAL
ENVIRONMENT.
THE 5H T2A RECEPTOR SEEMS TO
HAVE PERFECT THE BEST LOWERING
OF TRANSITION ENERGY COMPARED TO
OTHER SEROTONIN MAPS.
YOU CAN INTEGRATE NEURAL
TRANSMITTER INFORMATION.
I'M AT SIX MINUTES SO I'LL SAY
WE ALSO VALIDATED THIS IN AN DMT
STUDY.
WE SAW A PERSISTENT ENERGY
CORRELATED WITH ENERGY AND
PERSISTENT ACCEPTANCE SO I'LL
STOP THERE.
>> THANK YOU, AMY.
THOSE ARE FANTASTIC EXAMPLES
MUCH WEAVING THE THEORY
MODELLING AND MEASUREMENTS WE
CAN PERFORM.
THE NEXT SPEAKER IS DR. SHINE.
>> ALL RIGHT.
CAN YOU SEE THAT?
YES.
>> AWESOME.
THANK YOU SO MUCH FOR HAVING ME.
MY NAME IS MAC.
I'M SPEAKING TO YOU FROM THE
DARK UNDER SIDE OF THE WORLD IN
AUSTRALIA WHERE IT'S JUST PAST
MIDNIGHT SO APOLOGIES IF I SLUR
MY WORDS ORDER THROW IN SWEAR
WORDS AND PLEASED TO PRESENT
SOME OF OUR WORK.
WE ARE DOING MODELS EXACTLY LIKE
THE KINDS YOU JUST HEARD ABOUT
THE DIGITAL TWINS BUT USING
MODELS FRAMED AT THE SAME SCALE
THINKING ABOUT THAT MACRO SCALE
ORGANIZATION AND TRYING TO
UNDERSTAND WHAT WE CALL THE
SYSTEMS LEVEL ORGANIZATION OF
THE BRAIN.
AND SO I THINK ONE THING THAT IS
ABUNDANTLY CLEAR WHEN WE LOOK AT
THE NEUROSCIENCE FROM AFAR AND
ZOOM OUT IS THAT WE ARE STILL EN
OUR INFANCY AND TRYING TO MAP
THE BRAIN IN FRONT OF US IN THE
RIGHT WAY AND YOU SEE A TON OF
BEAUTIFUL AT WHAT WE CALL THE
MICROSCOPIC SCALE AND INDIVIDUAL
NEURONS OR POPULATIONS OF
NEURONS RECORDED WITH SOME OF
THESE COOL NEW TECHNIQUES AND
CALCIUM ENERGIES AND PHOTON
IMAGES TO GIVING A RICH DETAILED
UNDERSTANDING OF THE ANATOMY OF
THE BRAIN AND ARE FORCED TO TAKE
THE TELESCOPE AND USE WHOLE
BRAIN IMAGING AND MEG AND
FUNCTIONAL MRI AND THE TRICKY
PART IS THE DATA YOU COLLECT AT
DIFFERENT SCALES OFTEN LOOKS
DIFFERENT FROM ONE ANOTHER AND
IT'S DIFFICULT TO MAKE STRONG
CONNECTION BETWEEN ONE OF THE
BEAUTIFUL CAUSAL WORK DONE AT
THE MICROSCALE AND THE EMERGENT
PROPERTIES WE SEE WHEN WE
MEASURE MASS NEURAL ACTIVITY.
TO MAKE PROGRESS ON THE FRONT
AND WE THINK CAREFULLY ABOUT THE
ORGANIZATION BRAIN AND THEN TRY
TO MAP WHAT WE SEE TO THE NEURAL
IMAGING SCALE AND THE WHOLE
BRAIN SCALE AND THE WAY WE DO
THAT IS PUT COMPUTATIONAL MODELS
AND BIO PHYSICAL MODELS AND TRY
TO BRIDGE ACROSS THE DIFFERENT
SCALES.
SO SO WHEN YOU COME AS AN
OUTSIDER I HAVE A BACKGROUND IN
MEDICINE RATHER IN PHYSICS, WHEN
YOU COME IN AS AN OUTSIDER AS
CHRIS MENTIONED AT THE START
MODELLING CAN SEEM INTIMIDATING
AND IT CAN EVEN BE TO PEOPLE
THAT WILL ARE CAREERISTS IN
THESE DIFFERENT FIELDS.
I THINK IT'S HELPFUL TO THINK
WHAT MODELS ARE OUT THERE AND A
SIMPLE WAY TO PARS THINGS AT THE
START IS TO THINK WHETHER THE
MODEL IS ATTEMPTING TO HAVE RICH
ANATOMICAL DATA AND TRY TO MIMIC
EVERY TYPE OF CELL IN THE
CORTICO THALAMIC LOOP AND THE
PROBABILITY CONNECTIONS IN THAT
SECTOR -- CIRCUIT APPROACH AND
HERE WE MIGHT HAVE SOMETHING
LIKE THE FAMOUS ICING MODEL OF
MAGNETISM IT'S A BIT LIKE A
BRAIN AND THE BRAIN NEURON
FIRING AND THE BLUE MAY BE THE
BRAIN NOT FIRING.
HERE WE HAVE GOOD CONTROL OVER
MATHEMATICS BUT IT'S NOT LIKE
THE BRAIN.
IT'S HELPFUL TO THINK OF THE
BENEFITS AND COSTS OF EACH OF
THESE DIFFERENT TYPES.
IN THE ANATOMICAL CASE WE HAVE
EXPLICIT NEURAL ANATOMY AND WHAT
SOME OF THE CONS AND THERE'S
NUMEROUS PARAMETERS AND IT'S
REALLY DIFFICULT TO DRAW LINKS
TO CLINICAL IMAGING.
INTERPRETABLE MATHEMATICALLY YOU
CAN OFTEN GET ANALYTICAL
SOLUTIONS AND PUSH THE
MATHEMATICS AROUND DEEPLY AND
UNDERSTAND AND SCALE THEM.
ONE OF THE CHALLENGES THE MODELS
OFTEN DON'T MATCH TO THE
COMPLEXITY OF NEURAL ANAT --
ANATOMY.
AND EYE --
AND A TRADE-OFF IS TO USE THE
LURE OF RANDOMNESS TO OUR
ADVANTAGE.
WITH CAN TAKE AN INDIVIDUAL
FIRING OF A LITTLE NEURON ON THE
LEFT AND IMAGINE THE AMOUNT OF
CURRENT WE HAVE TO INJECT IN THE
NEURON TO GET IT TO SPIKE AT
ALL.
WE KNOW FROM OUR UNDER GRADUATE
NEUROSCIENCE IT TAKES A BIT TO
GET PAST THE FIRING POTENTIAL IT
THEN GETS TO ITS CEILING.
IF WE TAKE THE SIMPLEST
ASSUMPTION A GROUP OF NEURONS WE
HAVE AT SOME SCALE IS RANDOM FOR
ONE ANOTHER AND THIS IS
OBVIOUSLY AN ASSUMPTION THAT
COMES WITH SOME CAVEATS IF WE
MAKE THAT WE CAN ASSUME THAT
VARIABLE THAT IS NOW SMOOTHED
OUT AND WE ESSENTIALLY GET BACK
THIS SIGMOID MARKER YOU OFTEN
SEE A TON IN THE NEURAL MASS
MODELLING LITERATURE.
NOW WE CAN MESS AROUND WITH A
WELL KNOWN FUNCTION ON THE RIGHT
AND SAY SOMETHING ABOUT HOW THE
MASS ACTS OF THE NERVOUS SYSTEM
MAY HAVE WORKED WITH THE
ASSUMPTIONS.
THAT'S NOT ALWAYS THE BEST
ASSUMPTION BUT IT GIVES US A
TICKET TO THE GAME TO START
MAKING CHANGES AT THIS MORE
ABSTRACT LEVEL BUT IN A WAY THAT
HAS SOME NEURAL PLAUSIBILITY.
LET ME WALK YOU THROUGH ONE CASE
STUDY.
THIS IS ONE OF THE COOLEST
RESULTS I'VE SEEN IN THE LAST
FEW YEARS AND WE WENT IN AND
ANESTHETIZED A NUMBER OF MACAQUE
MONKEYS AND PUT THIS IN THE
CENTRAL LATERAL THALAMUS AND
STIMULATED WITH 50 HERTZ
STIMULATION AND WAKE THE ANIMAL
UP FROM ANESTHESIA WHICH IS COOL
AND MAKE CHANGES IN THE
ELECTROPHYSIOLOGICAL CHANGES
FROM THE MACAQUE AND WE WERE
INTERESTED WHETHER WE CAN
RECREATE THIS IN A NEURONAL MASS
MODEL AND WENT TO AN OVERLOOKED
FEATURE OF THE THALAMIC ANATOMY
AND THE THALAMUS CONTAINS TWO
TYPES OF PROJECTIONS TO THE
CEREBRAL CORTEX THE ONE IS ON
THE CORE TYPE.
YOU CAN IMAGINE THE RETINAL CELL
HITTING AND PASSING IT ON TO THE
CEREBRAL CORTEX.
THE AREA STIMULATED IS MORE RICH
IN THE MATRIX TYPE AND PROJECTS
TO THE GRANULAR OF THE CORTEX.
THE COOL THING IS WE CAN BUILD
OF MODEL OF THIS AND TAKE A
NEURAL MASS MODEL BUILT ON THE
CORTICO THALAMIC LOOP AND WIRE
IN THIS POPULATION AND THEN GO
IN THIS MODEL AND LOOKS LIKE
ANESTHETIZED AND WAKE IT UP AND
RECOVER DIFFERENT SIGNATURES WE
SEE IN THE COMMUNITY AND PUSH
THE MODEL AND FIGURE OUT WHY IT
DOES WHAT IT DOES AND TURNS OUT
STIMULATING THESE AS YOU WAKE UP
THE REST OF THE BRAIN MORE
QUICKLY THAN YOU CAN IN THE
CORTEX.
THE REASON PEOPLE IN THE
COMMUNITY MIGHT BE INTERESTED IS
IT TURNS OUT IN PARKINSON'S
DISEASE THEY CONTACT THESE TYPES
IN THE ANTERIOR VENTRAL NUCLEUS
AND CAN COMBINE THE PROBES IN
THIS CASES AND COME WITH THE
ASSUMPTIONS WE MAKE BUT THEY'RE
INTERESTING BECAUSE WE CAN START
TO MAKE PROGRESS UNDERSTANDING
THE LINKS BETWEEN THE DIFFERENT
SCALES.
THANK YOU VERY MUCH AND WE'LL BE
HAPPY TO CHAT IN THE DISCUSSION.
>> THANK YOU.
THAT WAS GREAT.
I THINK IT ILLUSTRATES FROM THE
PRAGMATIC STANDPOINT SOMETIMES
THE ANSWER TO THE QUESTION, WHAT
MODEL SHOULD I USE IS THE
SIMPLEST ONE I CAN FIND.
BUT YOU SACRIFICE THINGS IN THAT
AND SORT OF MISS THE OPPORTUNITY
TO EXPLORE UNDERLYING BEHAVIOR
AND DETAILS.
THANKS VERY MUCH.
THAT WAS GREAT.
OUR LAST SPEAKER IS DR
DR. PETERCHEV.
>> HELLO AND THANK YOU FOR THE
INVITATION.
I WILL BE TALKING ABOUT THE MOST
GRANULAR LEVEL SO FAR WITH
MODELLING.
WE HAVE THE INPUT SIDE OF TRANS
CRANIAL STIMULATION AND ELECTRIC
AND MAGNETIC STIMULATION.
AND THIS IS APPROVED FOR VARIOUS
THERAPEUTIC INDICATIONS
INCLUDING DEPRESSION, OBSESSIVE
COMPULSIVE DISORDER AND
MIGRAINES AND RESEARCHED FOR
BASIC AND CLINICAL APPLICATIONS.
SO HOW DO THEY WORK?
HOW CAN WE LEVERAGE THIS
UNDERSTANDING TO GET TO NEW
PARADIGMS?
AND GOING FROM THE BUILDING
MODELS AND UNDERSTANDING AND OF
COURSE THE FIRST LEVEL OF
INFORMATION IS WHERE YOU PLACE
THE COIL OR ELECTRODES AND WHAT
CURRENT YOU SEND THROUGH THEM.
THIS ALREADY HAS EXPLANATORY
POWER AND YOU GET THE FINGER
TWITCH.
HOWEVER IT STARTS TO GETS
COMPLICATED.
DEPENDING ON THE CHARACTERISTICS
OF THE PULSE TO THE CORTEX YOU
HAVE DIFFERENT RESPONSES.
WE CAN START TO CREATE MODELS
THAT REACH THE BRAIN BECAUSE
THERE'S THE ACTIVE INGREDIENT OF
STIMULATION AND THIS CAN ADD
MORE EXPLANATORY POWER.
OF COURSE, WHAT REALLY MATTERS
IS HOW THE ELECTRIC FIELD
PRODUCES NEURONS IN THE CORTEX
AND GET MORE EXPLANATORY POWER
LY FROM THAT AS WELL.
YOU CAN THINK OF THIS AS
PERTURBATION TO THE LEVEL OF THE
PULSE YOU SEND EXTERNALLY TO
PERTURBATIONS IN THE ELECTRIC
FIELD AND NEURAL RECRUITMENT AND
CAN KEEP GOING AND CAN HAVE
PERTURBATIONS IN THE MICRO
COLUMNS AND KEEP GOING AND LINK
WITH ALL THESE BEAUTIFUL MODELS
MY COLLEAGUES JUST PRESENTED OF
COURSE THERE'S CHALLENGES WITH
THAT.
THERE'S MORE AND MORE KNOWN IN A
CERTAIN PARAMETER AND
COMPUTATION COMPLEXITY.
THIS FOR A WHOLE FIELD TO
HANDLE.
I WANTED TO SHOW A COUPLE
EXAMPLES FROM OUR WORK.
SO ONE VERY TRIVIAL ASPECT IS
THE KIND OF MINUTIA OF THE DATA
YOU FEED INTO THE MODELS.
AND ONE I THINK SO INCREASE HAIR
THICKNESS.
AN EXTRA ONE ONE MILLIMETER OF
HAIR THICKNESS INCREASES THE TMS
IN THE BRAIN AND ON AVERAGE IT'S
2 MILLIMETERS WITH A PRETTY WIDE
RANGE.
SO WELL, WE NOW HAVE A TOOL TO
MEASURE IT AND ADD TO OUR TMS
MODELS.
WE GO FROM EXPLAINING 27% WITH
THE INDIVIDUAL THRESHOLDS TO 31%
WHICH SOUND SMALL BUT IT'S
REMARKABLE GIVEN HAIR THICKNESS
ACCOUNTS FOR 10% OF THE COIL TO
BRAIN DISTANCE.
THEN GETTING IN THE BRAIN IT
GETS MORE COMPLICATED.
THERE YOU HAVE ALL KINDS OF
NEURONS AND CORTICAL LAYERS AND
SO ON AND CAN MAKE MODELS OF
THESE TO UNDERSTAND HOW THE
ELECTRIC FIELD MODELS AND YOU
CAN DO VALIDATION OF THESE BUT
ALWAYS GOOD TO DO MORE.
WHAT CAN WE DO ONCE WE HAVE THE
MODELS?
ONE INTERESTING EXAMPLE BUT
CHANGE THE POLARITY OF THE
FIELD.
SAY YOU HAVE ONE PULSE FROM
POSTERIOR TO INTERIOR IN THE
CORTEX WHICH ACTIVATES THE
MUSCLES IN THE HAND AND MEASURE
THE FINGER TWITCHING AND HAVE
ONE LATENCY AND THEN YOU CHANGE
THE PULSE DIRECTION.
NOTHING ELSE JUST THE POLARITY
OF THE FIELD BASICALLY AND HAVE
THE LONGER FINGER TWITCH.
WE'RE ACTIVATING A DIFFERENT
NEURAL POPULATION.
MAYBE THAT'S WHAT'S HAPPENING
BUT WE DON'T KNOW REALLY HOW IT
HAPPENS AND CAN USE THE
MULTI-SCALE MODELLING TO
ACTUALLY EXPLAIN THAT
PHENOMENON.
YOU SEE THE CROSS SECTIONS AND
YOU ACTIVATE MORE POSTERIOR
NEURONS AND WITH AND THE OTHER
YOU ACTIVATE MORE ANTEARIOR --
AN ANTERIOR DIRECTION AND YOU
END UP WITH ACTIVATING MORE
POSTERIOR NEURONS IN THE GYRUS
AND MORE ANTERIOR WITH THE
ANTERIOR-POSTERIOR PULSE.
WE NOW FROM MORE INVASIVE
NON-HUMAN PRIMATE THEY HAVE
CONNECTS WITH THE SPINAL TRACT
AND MORE INTERIOR NEURONS HAVE
MORE INDIRECT CONNECTIONS.
AND SO SIGNAL TRAVELS TO
SYNAPSES BEFORE GOING TO THE
CORTICAL SPINAL NEURONS DRIVING
THE TRACK.
WHY DOES IT MATTER?
WELL, WITH THE APPLICATIONS OF
MODULATION AND WHEN YOU
STIMULATE REPEATEDLY WITH PULSES
WITH DIFFERENT DIRECTIONS YOU
CAN GET VERY DIFFERENT RESULTS.
WITH T.A. PULSES YOU GET STRONG
FACILITATION.
WITH THE OPPOSITE DIRECTION YOU
HAVE STRONG INHIBITION AND BY
BASIC PULSES OF ALL DIRECTIONS
YOU GET IN BETWEEN EFFECT.
IT MATTERS FOR THE MODULATION.
SO THIS ALSO STARTS OUR
DISCUSSION AND HOW MULTI-SCALE
MODELLING INCLUDING COUPLING
BETWEEN THE STIMULUS AND NEURAL
ACTIVATION CAN HELP INCLUDING
WITH MECHANISTIC INSIGHTS TO
INFORM NOVEL PARADIGMING AND
INDIVIDUALIZED DOSING
POTENTIALLY AND COMPARE
NON-INVASIVE WITH INVASIVE
RESULTS AND USE MRI AND HAIR
THICKNESS AND MORE DYNAMICS AND
OPPORTUNITY THAT I HOPE WE'LL
ALL DISCUSS IT'S THE DATA AND
THERE'S TRIVIAL ASPECTS THE
LOW-HANGING FRUIT.
JUST RECORD ALL THE STIMULATION
PARAMETERS AND RECORD THE HAIR
THICKNESS.
LIKE ALL THIS MATTERS.
DOCUMENT THAT TO MAKE SENSE OF
THE EXPERIMENTAL DATA AND MODEL
IT.
SOME THINGS ARE EASIER AND IF WE
HAVE ALL THE PIECES AND
EVERYTHING IS RELATIVELY EASIER.
IT'S HARDER BUT I THINK WHAT
WE'LL GET IN THE FUTURE IS
INCORPORATING UNDERSTANDING OF
THE NEURAL RESPONSE TO EXTEND
NEURAL MODELLING AND THE
PRECISION OF METHODS LIKE THE
BRAIN SHIFTS DOING MRI SCANS AND
THE MORPHOLOGY ALL COMPLEX PUT
THERE'S DATA COMING AND
VALIDATION IS VERY IMPORTANT.
THERE HAS TO BE MORE AND MORE OF
THAT.
AND DOING NON-INVASIVE
STIMULATION AND DATA SHARING AND
CURATION IS IMPORTANT TO ENABLE
MODELLING STUDIES.
THANK YOU.
>> THANK YOU.
I THINK ONE OF THE THINGS YOUR
TALK HIGHLIGHTS IS THAT IN THESE
AREAS OF RESEARCH WE'RE OFTEN
INTERESTED IN THE TEMPORAL
DYNAMICS AND HOW THINGS UNFOLD
OVER TIME RANGING FROM
MILLISECONDS TO SECONDS TO
MINUTES, HOURS, DAYS, WEEKS,
MONTHS.
AND WHAT CAN BE INSTRUCTIVE IN
THE MODELS IS IF YOU WANT TO
LOOK OVER SOME TIME SCALE OUT TO
SECONDS OR MINUTES OR HOURS OR
LONGER YOU NEED TO HAVE
MECHANISMS IN YOUR MODEL THAT
WORK OVER THOSE TIME SCALES.
AND IF YOU DON'T, THEN IT'S AN
OPPORTUNITY TO THINK OH, WHAT IS
IT MISSING.
WE GET TO ASSEMBLE THESE MODELS
AND PUT IN THE FEATURES WE WANT
AND IT CAN OFTEN HIGHLIGHT
POTENTIAL NEW MECHANISMS THAT
MIGHT HELP THAT.
SO I WANT TO NOW JUST OPEN IT UP
TO THE PANELISTS FOR QUESTION
AND DISCUSSION.
I DON'T KNOW.
SOMETIMES I DON'T ALWAYS NOTICE
THE HANDS IF PEOPLE ARE RAISING
THEIR HANDS.
>> I WOULD SAY THAT I THINK IT'S
REALLY FASCINATING SEEING ALL
THE MODELS AT DIFFERENT SCALES.
I THINK THERE'S OPPORTUNITIES TO
COUPLE THEM.
I WAS SHOWING SEVERAL STAGES OF
BOTTOM UP, GROUND UP MULTI-SCALE
MODELS AND THAT DASH ARROW
DIRECTLY LINKS WITH MODELS
SHOWED BY MY COLLEAGUES AND CAN
BE FASCINATING TO DO THAT AND GO
TO THE MACROSCOPIC SCALE PIECING
THE MODELS TOGETHER AND THEN
LOOK AT THE TIMEOUTS AND DO IT
IN HEALTHY SUBJECTS.
IT'S VERY SAFE AND USED
CLINICALLY AND HIGH RELEVANCE SO
THEN GO FROM STIMULUS AND
COMPARE THIS EXPERIMENTAL DATA
LIKE IMAGING AND fMRI AND
OPPORTUNITIES FOR MULTI-SCALE
MODELLING.
>> ANDREAS HAS HAS A HAND UP.
>> IT WAS A FANTASTIC PANEL.
>> ONE QUESTION ABOUT I THINK WE
HAD SIMILAR DISCUSSION YESTERDAY
BUT YOU ARE THE EXPERTS ON THIS
WITH THE IDEA OF WHAT TYPE OF
ANSWERS WILL WE GET AS A LOWER
HANGING FRUIT USING DYNAMICAL
SYSTEMS AND WILL THEY BE IN THE
FORM OF WE HAVE GOOD MODELS TO
SIMULATE THINGS OR CAN MAYBE
CONDENSE THEM DOWN YOU THINK IN
THE FUTURE LIKE UP REGULATE THE
CIRCUIT OR THAT AND WONDERING
WHAT ARE WE HOPING FOR IN THE
NEARER FUTURE AND MAYBE IN THE
LONGER FUTURE.
WE'D LOVE TO HEAR YOUR THOUGHTS
ON THIS.
>> NICE TO SEE YOU.
WE ARE COLLABORATING AND I THINK
DEEP BRAIN STIMULATION IS A GOOD
OPPORTUNITY.
ALSO THE CONSIDERATIONS ARE NOT
SO DRAMATIC.
SO BECAUSE YOU USUALLY DO THE
MANUAL TUNING ANYWAYS AND SIDE
EFFECTS AND THERE'S NOT THE
DANGER OF DOING THAT.
FOR ME IT'S A LOW HANGING FRUIT
AND I'M HAPPY ABOUT OUR
COLLABORATION AND WORKING WITH
CONTACT TO CLINICAL GROUPS AND
GETTING THE DATA SO THIS IS
FANTASTIC AND COMBINING WITH
WHAT YOU HAVE DONE SO FAR AND
LOOKING AT THE PREDICTION OF THE
OUTCOME AND BASED ON STAFFIC CON
EKSZ AND INCLUDE THE DYNAMICS
AND SEE IF IT'S BENEFICIAL FOR
THE PATIENT AND MAYBE NOT WE'LL
FIND IT OUT.
>> THANK YOU.
I VIKTOR HAD HIS HAND UP FIRST.
>> THANK YOU.
HELLO EVERYONE.
THANK YOU VERY MUCH FOR THE
LOVELY PRESENTATIONS ALL FOUR OF
YOU.
YOU WERE ALL TALKING OR
ACKNOWLEDGING THE MULTISCALE OF
THE BRAIN AND THERE'S ONE ASPECT
THAT GENERATES LOTS OF ISSUES
FOR ALL OF US IN TERMS OF MODEL
VALIDATION AND IS THE
MULTI-SCALE NATURE OF THE BRAIN.
EVERY MULTI-SCALE SYSTEM HAS AS
A CONSEQUENCE DUE TO THE
MODELLING NATURE HAS THE
PROPERTY OF THE GENEROUSITY OF
THE SYSTEM ON ONE HAND AND ON
ONE SIDE DEGENEROUSITY IS GOOD
AND YOU CAN SHOW THIS
MATHEMATICALLY.
ON THE ONE SIDE WE DEAL WITH
DEGENERASY AND IT HELPS THE
BRAIN AND STILL GENERATE THE
SYNC UP BUT YOU WANT TO DEAL
WITH THE SIGNALS AND DEALING
WITH NON-IDENTIFIABLE ISSUES.
THIS IS A HUGE OBSTACLE FOR US
WHEN TRYING TO INTERPRET THE
SIGNAL.
SIMPLE OPTIMIZATION DOES NOT
WORK BECAUSE OF THE ISSUES IN
TERMS OF NON-IDENTIFIABILITY CAN
COME IN THROUGH DE-GENEROUSITY
ON ONE SIDE OR THE SYSTEM IS NOT
WELL CONSTRAINED.
NONE OF YOU HAVE SPOKEN ABOUT
MODEL VALIDATION BUT WE'RE
RUNNING INTO THIS ISSUE IN THE
MULTISCALE SYSTEM AND WOULD LIKE
YOUR THOUGHTS ON THIS BECAUSE IF
WE WANT TO BRING THE MODELS INTO
CLINICAL APPLICATIONS AS PETRA
JUST SAID WE NEED TO KNOW HOW
WELL WE UNDERSTAND THE SIGNALS
WHETHER WE CAN IDENTIFY THE
MECHANISMS OR JUST CORRELATE
THEM.
>> I SEE MULTIPLE PEOPLE HAVE
THEIR HANDS UP.
MAYBE WE'LL STAY ON THE TOPIC
FOR A MOMENT AND I KNOW MIRIAM
YOU HAND YOUR HANDS UP AND MAYBE
THEY'RE ON DIFFERENT TOPICS SO
WE'LL COME BACK IN A MINUTE.
AMY, GO AHEAD.
>> SO AND I THINK MOST
COMPUTATIONAL MODELERS THINK OF
THE CURSE OF DIMENSIONALITY AND
THE FINER SCALE WITH MODELS THE
MORE PARAMETERS WE HAVE TO FIT.
IT'S GOING TO NEED MORE AND MORE
DATA IN ORDER TO GET RELIABLE
ESTIMATES OF THOSE.
SO I THINK ONE BIG THINK --
THING WE COULD DO IS COMBINE
DATA SETS AND MAKE A LARGE SCALE
EFFORT HA HARMONIZE DATA SETS
AND HAVE LARGE DATA SETS TO WORK
WITH TO IDENTIFY SOME SORT OF
PERHAPS CANONICAL LAWS THAT
OCCUR IN THE BRAIN IN EVERYONE'S
BRAINS AND THEN ALSO BE ABLE TO
HAVE MODELS THAT ARE -- HAVE
ENOUGH PARAMETERS TO CAPTURE
THAT DIVERSITY ACROSS POPULATION
BUT NOT SO MUCH WE HAVE
NON-IDENTIFIABILITY TO A CERTAIN
EXTENT.
SO I THINK THESE LARGE SCALE
COMPILATIONS OF DATA WOULD HELP
IN THAT REGARD AS WELL AS
INTERCOMBRATING MULTI-SCALE
MODELS AND PROBING WHAT SCALE WE
NEED TO GET USEFUL INFORMATION
CLINICALLY.
IF WE ONLY NEED TO KNOW THE
MACRO SCALE ACTIVATION PATTERN
CHANGES THAT OCCUR IN RESPONSE
TO A STIMULATION, THEN MAYBE
THAT'S ALL WE NEED TO MODEL.
>> ONE THING THAT PROBABLY GOES
WITH THAT IS WHEN THE NUMBER OF
PARAME
PARAMETERS EXPLODE DO A
SENSITIVITY ANALYSIS AND PETRA I
THINK YOU WERE.
>> CONSIDER THE PROBLEM WIN FIVE
MINUTES AND IT'S NOT ENOUGH TO
GO IN DEPTH TO THE TOPIC.
WHAT I WANT TO EMPHASIZE IS THIS
IS THE NATURE OF OUR BRAIN AS
SAID BY VIKTOR TO BE REDUNDANT
AND EMBRACE IT.
IT'S NOT THE BACK OF OUR
MODELLING APPROACH BUT IT
REFLECTS WHAT THE BRAIN IS.
THEREFORE WE NEED TO COME UP
WITH METHODS AND WHAT WE'RE
DOING LIKE PARAMETER LEARNING.
THIS IS WHAT HE THIS BRAIN DOES.
WE BASICALLY USE METHODS TO
GENERALIZE.
SO IT'S A NICE A.I. AND THE
MODELLING COMING CLOSER AND
CLOSER.
AND THE BORDERS ARE FWETH MORE
-- BECOMING MORE FUZZY AND LESS
CLEAR.
AND WE'RE GOING AWAY FROM
STATISTICAL AND USE A MODELLING
TOOL PARAMETER LEARNING WHICH
MIMICS WHAT OUR BRAIN IS DOING
WHEN IT IS LEARNING AND
DEVELOPING.
BUT WITH WHAT I WOULD BE
INTERESTED IN AND YOU ARE
THINKING ABOUT IT A LOT VIKTOR
AND WHAT ARE YOU DOING ABOUT THE
PROBLEM?
>> CAN I ANSWER?
CAN I RESPOND TO THIS?
>> SURE.
I'LL TRY TO KEEP THE ANSWER VERY
SHORT.
PETRA, I LIKE YOUR RESPONSE.
WHEN YOU SAID WE NEED TO EMBRACE
IT BECAUSE IT'S PART OF THE
NATURE SO WE HAVE ESSENTIALLY
THE PARAMETER IF YOU WISH THAT
ALLOW DIFFERENT REALIZATIONS OF
THE BRAIN.
WE NEED TO LIVE WITH
NON-IDENTIFIABILITY BECAUSE IT
CAN COME EITHER BECAUSE THE
PROBLEM NOT SUFFICIENTLY
CONSTRAINED OR BECAUSE THE
PROBLEM IS ACTUALLY
INTRINSICALLY AND ENDOGENOUSLY
IDENTIFIED AND THIS IS WHAT THE
BRAIN WORKS WITH ALSO.
THE WAY I THINK ABOUT THIS AND I
FULLY AGREE WE SHOULD EMBRACE
IT.
THE WAY TO WHY EMBRACE IT IS TO
ADAPT THE TOOLS NOT TRYING TO
FIND THE BEST PARAMETER SETTING
BUT WORKING WITH DISTRIBUTIONS
SAMPLING MULTIPLE SOLUTIONS
PROVIDING US FOR EVIDENCE OR
LIKELIHOOD FOR POSSIBLE
SOLUTIONS AND IF WE GET THE
INFORMATION OUT OF THIS MEANING
WE CANNOT INFER ANYTHING BECAUSE
THE PROBLEM IS NOT CONSTRAINED
AND WE MUST KNOW THAT.
THE CLINICIAN MUST KNOW THAT
WHEN HE, SHE IS MAKING A
DECISION AND THE PROBLEM IS NOT
WELL CONSTRAINED.
THE ONLY WAY OF DEALING WITH
THAT IS IN A PROBABILISTIC WAY
AND IF IT'S IN A DIFFERENT
MANNER IT DOESN'T MATTER.
THAT'S NOT THE POINT.
>> THANKS.
>> THAT TOUCHES ON THE TOPIC OF
UNCERTAINTY QUANTIFICATION.
THAT'S AN OBSCURE TERM AND
QUANTIFYING AND VISUALIZING
VARIABILITY.
I WANT TO BRING IN THE OTHER TWO
DISCUSSANTS.
I DON'T KNOW WHO RAISED THEIR
HAND FIRST.
MARYAM I SAW YOU FIRST.
>> GREAT.
THE TOPIC I WANTED TO DISCUSS
RELATE TO WHAT WAS JUST
DISCUSSED AND VALIDATE THE
MODELS.
THE WORK ON A.I. AND STATISTICAL
MODELLING FOCUSSED ON THE
PREDICTION OF MODEL AS OBTAINED
TO CORRELATION.
WE HAVE A GREAT OPPORTUNITY
PERHAPS FOR CAUSAL VALIDATION
BECAUSE WE NOT ONLY ARE
OBSERVING THE OUTPUT OF THE
SYSTEM BUT PERTURB IT THROUGH
INPUT AND CAUSALLY VALIDATE
MODEL PREDICTIONS AND HOW DO WE
BUILD THE MOLES AMENABLE TO
CAUSAL PREDICTION.
THAT RELATES TO CONTROL THEORY.
IF YOU BUILD A COMPLICATED MODEL
PERHAPS YOU CANNOT BUILD THE
OPTIMAL INPUTS YOU CAN THEN USE
TO PERTURB THE OUTPUT OF THE
MODEL.
I WANTED TO TOUCH ON THIS
TRADE-OFF BETWEEN MODEL
COMPLEXITY TO GET CAUSAL VALLING
DAY -- -- VALIDATION IN MY WORK
AND I LOOK AT THE OPPORTUNITY AS
A FIELD TO THINK OF MODELS
CONTROLLABLE SO WE CAN CAUSALLY
VALIDATE PREDICTIONS.
I WANTED TO SEE WHAT THE OTHER
PANEL MEMBERS AND SPEAKERS THINK
ABOUT THAT AS WELL.
>> MARYAM, THANKS.
CAN YOU TAKE A MOMENT AND
EXPLAIN TO PEOPLE BECAUSE WE
COLLECTIVELY HAVE USED THE WORD
MODEL IN A BUNCH OF WAYS AND
THAT WORD IS OFTEN FAMILIAR AND
WE CONTEXT SWITCH QUICKLY.
AND WE HAVE A DATA-DRIVEN MODEL
OPPOSED TO STARTING FOR A BIO
PHYSICAL MODEL.
AND YOU DESCRIBE WHAT THE DATA
DRIVEN MODELS ARE.
>> YEAH.
FROM A DATA-DRIVEN PERSPECTIVE
USUALLY WHAT WE BUILD THE MODELS
TO DO IS TO FOR EXAMPLE DESCRIBE
THE EVOLUTION OF NEURAL ACTIVITY
PATTERNS.
THIS WE CALL UNSUPERVISED
MODELLING BECAUSE WE'RE
MODELLING THE BRAIN DATA
AGNOSTIC TO ANY BEHAVIORAL
CONTEXT AND YOU HAVE NEURAL AND
DATA AS WELL AS BEHAVIORAL
LABELS AND BUILD THE SUPERVISED
MODELS TO RELATE IT TOGETHER.
THESE BRAIN BEHAVIOR MODELS THAT
ARE DATA DRIVEN LARGELY FOCUS ON
PREDICTION TO ESTABLISH
CORRELATION.
YOU BUILD A MODEL AND USE IT TO
PREDICT BEHAVIOR AND THEN LOOK
AT THE CORRELATION OF TWO
BEHAVIORAL LABELS A WAY OF
VALIDATING THE MODELS.
WHAT I'M TRYING TO BRING UP IS
WHAT IF WE WANT TO CAUSALLY
VALIDATE THE MODELS.
WHAT WE CAN DO IS MODEL THE
EFFECT OF PERTURBATION IN THE
MODELS AND HAVE A MODEL THAT
DESCRIBES HOW DOES THIS
PERTURBATION AND CHANGES THE
BEHAVIORAL OUTCOMES AND THEN
APPLY THAT UNVALIDATED AND MAKE
THE RIGHT PREDICTION.
THAT WOULD ESSENTIALLY MOVE US
TOWARDS CAUSAL VALIDATION OF THE
MODELS RATHER THAN
CORRELATION-BASED VALIDATION.
BY DATA DRIVEN MODELS
ESSENTIALLY DESCRIBING DYNAMIC
DATA AND RELATIONSHIP TO
BEHAVIORAL LABELS AND
POTENTIALLY WHAT I'M ARGUING FOR
IS TO MODEL THE OF PERTURBATION
SUCH THAT WE CAN SALVAGE
CAUSALITY.
>> SURE, THANKS.
SO I JUST WANT TO ASK, IG NACIO,
LET'S HEAR WHAT MAC SAYS ON THE
TOPIC AND THEN I'LL COME TO YOU.
THANKS FOR YOUR PATIENCE.
>> NO WORRIES.
I DON'T HAVE SOLUTIONS TO REAL
PROBLEMS BUT I WANTED TO PUT AN
INTERESTING FLAG OUT THERE FOR
US THAT THERE ARE NOW MORE THAN
EVER THESE AMAZING DATA SETS OUT
THERE WITH CAUSAL PERTURBATION
OF SPECIFIC CELL LINES IN MODELS
OFTEN OF RECEPTORS OR NEURAL
TARGETS THEN MATCHED TO WHOLE
BRAIN IMAGING OR PHYSIOLOGICAL
DATA AND I'M A BIG BELIEVER IN
OTHER GREAT MEASURES AND WILL
MAKE IMPACT IN THE LONG RUN BUT
CONCERNED WE DON'T HAVE
OBSERVATIONAL MODELS OF WHAT ARE
CAUSED BY THE STIMULATION
PARAMETERS AND EMBRACE THE IDEA
OF USING THE ANIMAL MODELS FOR
WHAT THEY'RE GOOD FOR AND I'M IN
THE HITTING THE CELLS AND NOT
THE GABAERGIC CELLS AND NOT
OTHER POPULATIONS VERSUS HITTING
ELECTROSTIMULATION AND IF WE CAN
TAKE THAT WE CAN START TO DEAL
WITH THE CHALLENGES AND WHETHER
IT'S MORE OF THE BIO PHYSICAL
MODEL.
IT'S A GREAT OPPORTUNITY TO
EMBRACE BOTH WORLDS GOING
FORWARD.
>> THANKS.
ONE THING THAT GETS TO AND I
DIDN'T MENTION THIS IN THE INTRO
IS ONE OF THE ADVANTAGES OF
MODELLING IS INFINITE
INSTRUMENTATION.
THAT'S A BLESSING, SOMETIMES A
CURSE.
YOU HAVE TO FIGURE OUT WHAT TO
DO WITH IT ALL AND MAKE SURE
IT'S REALISTIC BUT SOMEWHAT
RELATED TO THAT IS IN MODELS
WE'RE OFTEN TO DO THE CIRCUITRY
WE'RE LOOKING AT AND WE'RE ABLE
TO TEST IDEAS AND DO EXPERIMENTS
THAT WOULD BE DIFFICULT OR
IMPOSSIBLE TO DO
PHYSIOLOGICALLY.
I WANTED TO START AND HIGHLIGHT
THOSE THINGS BECAUSE I THINK
THOSE ARE REASONS WE TAKE FOR
GRANTED AND DON'T ALWAYS STOP
AND ARTICULATE BUT IT'S A HUGE
ADVANTAGE WHAT WE HAVE AS
EXPERIMENTALISTS TO COMBINE ALL
THE DATA WE CAN WHETHER IT'S
SYNTHETIC OR PHYSIOLOGICAL.
AMY, DID YOU HAVE A COMMENT ON
THIS TOPIC?
>> YES.
TWO QUICK POINTS.
THE DATA DRIVEN MODELS ARE
INTERESTING IN DIFFERENT WAYS
AND ONE IS IN THE AREA OF AN
EXAMPLE OF INDIVIDUAL
NEUROSCIENCE WHERE PEOPLE ARE
STUDYING THE HUMAN VISUAL SYSTEM
AND THEY'RE TRAINING ARTIFICIAL
NEURAL NETWORKS TO DO THE SAME
THING WHEN WE DO IMAGES, SEGMENT
OR IDENTIFY THE CONTENT OF AN
IMAGE.
THERE'S REALLY COOL WORK FROM
VARIOUS PEOPLE LOOKING AT HOW
THE ARTIFICIAL NEURAL NETWORK
TRAINING PROCESS RESULTS IN
SIMILAR ARCHITECTURES TO WHAT
OCCURS IN THE BIOLOGICAL SYSTEM.
I WANTED TO EMPHASIZE
DATA-DRIVEN MODELS MAY TELL US
SOMETHING ABOUT THE BIOLOGICAL
SYSTEM.
IT'S NOT JUST A BLACK BOX WE'RE
FEEDING IN SOME THING AND
GETTING OUT WHAT THE BRAIN IS
GOING TO DO WHEN YOU STIMULATE
IT IN THIS WAY.
IT CAN TELL YOU ABOUT THE
DYNAMICS OF THE SYSTEM.
AND THE OTHER ONE IS ONE OF THE
BENEFITS OF USING ARTIFICIAL
NEURAL NETWORKS IF YOU MAKE THE
ARCHITECTURE IN AN APPROPRIATE
WAY IT COWL GIVE A LOWER
DIMENSION REPRESENTATION WHICH
AGAIN GOES BACK TO OUR PROBLEM
WE HAVE IF WE HAVE TOO MUCH DATA
OR WE HAVE TOO MANY SORT OF
MODELS THAT WE'RE USING IT CAN
TELL US WHICH MODELS MIGHT BE
BETTER AND PROVIDE A WAY TO
REDUCE THE DIMENSIONALITY
WITHOUT LOSING DIMENSION FROM
EACH REGION.
>> THANKS.
>> THAT TOUCHES ON THE CONCEPT
OF EXPLAINABILITY A LOT OF TIMES
PURELY DATA-DRIVEN MODELS ARE
SOMEWHAT DIFFICULT TO EXPLAIN
AND MARYAM MENTIONED SUPERVISED
TRAINING AND TECHNIQUE TO
CONSTRAIN THAT AND SCIENTISTS
AND RECENTLY ONE THAT I'M AWARE
OF IS CHRIS ROSELL USING
SECONDARY A.I. MODELS TO MAKE
THE PRIMARY A.I. MODELS
EXPLAINABLE AND IDENTIFY LATENT
VARIABLES WHICH SEEMS CLEVER AND
A GOOD APPROACH.
ALSO IN THE INTRODUCTION I WAS
JOKING WHEN YOU MAKE A MODEL
IT'S LIKE AWHILE ANIMAL YOU HAVE
TO FIGURE OUT WHAT TO DO WITH
IT.
THERE'S PLENTY EXAMPLES OF LARGE
DATA-DRIVEN MODELS THAT BEHAVED
BADLY IN WAYS WE DIDN'T
ANTICIPATE AND MAY THINK OF HOW
TO CONSTRAIN THAT AND MAKE SURE
WE HAVE EXPLAINABILITY IN THE
END.
CLAYTON, GO AHEAD.
>> THIS IS A WONDERFUL
CONVERSATION.
OBVIOUSLY WE CAN HAVE SEVERAL
SESSIONS ON THIS.
I DO WANT TO COME BACK TO THE
CONTEXT OF COORDINATED EFFORT.
>> CLAYTON, WE'RE GETTING A
BUNCH OF REVERBERATION WHEN
YOU'RE TALKING.
>> THIS IS A WONDERFUL
CONVERSATION AND CAN DO THIS FOR
DAYS.
IT WOULD BE VALUABLE TO RECORD
THE CONTEXT OF COORDINATED
EFFORTS FROM DATA WE'RE LIKELY
TO GET FROM THOSE KINDS OF
STUDIES.
AND ON THAT POINT, ONE THING
THAT I HAVE BEEN HEARING AND I
THINK MAC TOUCHED ON A LITTLE
BIT BUT HAVE SEEN IT IN SEVERAL
DIFFERENT DISCUSSIONS IS THE USE
OF NON-INVASIVE IMAGES FOR
MODELS BEING USED.
I'M GOING IT MAKE A STATEMENT.
I'M NOT TRYING TO BE
CONTROVERSIAL BUT WOULD LOVE A
RESPONSE FROM THE PANEL ON THIS
AND THAT IS THAT FOR ALL THE
WONDERFUL INSIGHTS WE'VE GOTTEN
FROM DIFFUSION MRI AT THE END OF
THE DAY STREAMLINES ARE NOT
AXONS AND WOULD BE USEFUL TO
HEAR TO THE PANEL RESPOND TO
THAT AND DISCUSS WHAT THE
IMPLICATIONS ARE FOR MODELLING
AT LARGE BE IT BY PHYSICAL OR
DATA DRIVEN.
>> I COME FROM THE DIFFUSION
IMAGING FIELD AND THEY SRGED OUT
HOW DIFFICULT IT WAS AND AT A
HIGH LEVEL AND EMBRACE ALL THE
CHALLENGES.
THEY'VE MADE GREAT PROGRESS BUT
EVEN WITH THE CHALLENGES THEY'RE
JUST MAPPING CORTICAL ACTIVITY
AND I WOULD ARGUE WITH WHAT'S
GOING WRONG IN DEMENTIA,
PARKINSON'S DISEASE AND OTHER
DISORDERS ARE LIKELY PROBLEMS
WITH THE CORTICAL SYSTEM AND IT
DEVELOPS TAU PATHOLOGY AND CAN'T
MODULATE ANOTHER SUBCORTICAL
STRUCTURE AND IT'S MAYBE
DETECTABLE AT THE CORTICAL
LEVEL.
WE'RE STARTING TO I THINK
EMBRACE THE MOTION OF THE SYSTEM
OF THE BRAIN WORKING AS A WHOLE
REQUIRES US THINKING CAREFULLY
WHETHER THE MEASURES ARE
CONSTRAINING THE FUNCTION OF THE
SYSTEM OR ANOTHER MEASURE.
UNTIL WE TAKE THAT SERIOUSLY
WE'RE GOING TO KEEP MEASURING A
PART AND TAKING IT FOR THE
WHOLE.
I'M NOT TRYING TO SAY THE SKY'S
FALLING, I THINK WE CAN MAKE
GREAT PROGRESS HERE.
THERE'S EXCELLENT ANATOMICAL
DATA FOR EXAMPLE THE ALLEN BRAIN
MAPPED THE MOUSE CONNECTOME IN
EXCRUCIATING DETAIL AND USE THEM
TO ASK HOW THEY RELATE TO THE
HUMAN WHEN YOU PUSH THE NEEDLE
FORWARD.
IT WILL TAKE ENGINEERING AS WELL
AS UNDERSTANDING AND THOSE TWO
WORKING TOGETHER WILL BE GREAT
TO WATCH BUT IF WE DO THIS AS A
COMMUNITY WE'LL GET BETTER
ANSWERS ABOUT THE KINDS OF
EFFECTS WE EXPECT TO SEE TO
RECOVER FUNCTION.
>> THANKS.
I THINK ALSO YOU BROUGHT UP THE
LIMITS OF DIFFUSION IMAGING AND
IN THE BEST CASE RIGHT NOW THE
TACTOGGRAPHY WE GET ARE AND HAVE
TO BE CAREFUL BASED ON THE DATA.
AND WHAT WE'VE USED IS
CONVERGING EVIDENCE.
IF WE USE A TRACTOGRAPHY BASED
MODEL WE SHOULD BE ABLE TO
CONFIRM DIRECTLY OR INDIRECTLY
USING OTHER MODELS OR
PHYSIOLOGICAL RECORDINGS DURING
EEG OR IN TERMS OF FUNCTIONAL
IMAGING OR THE LIST GOES ON BUT
I THINK THAT'S A REALLY
IMPORTANT POINT AND MAYBE
SOMETHING WE HAVEN'T TOUCHED ON
SO MUCH HERE IS INTEGRATING THE
DIFFERENT TYPES OF DATA AND
SAYING WE HAVE A PREDICTIVE
RESULT.
>> THERE'S GERL POINTS
COLLECTIVELY ACROSS DIFFERENT
QUESTIONS.
I WANT TO POINT OUT THAT THERE'S
A FAMOUS QUOTE THAT ALL MODELS
ARE WRONG, SOME ARE USEFUL.
WE HAVE TO RECOGNIZE THERE'S NOT
A PERFECT MODEL OF THE BRAIN.
THE WAY I THINK OF THE MODELLING
EFFORT IS THAT WE ARE WORKING
ONE BRIDGE AT A TIME.
IT'S A COMPLEX EDIFICE WE'RE
BUILDING AND IT'S A MULTISCALE
SYSTEM AND A LOT OF THE
VALIDATION CAN BE DONE AT THE
GIVEN SCALE RATHER THE WHOLE
MODEL AND WE HAVE THE NEW
MEASUREMENT AND VALIDATE.
THAT'S ONE SCALE.
AND IT FEED FORWARD FROM THERE
TO THE OTHER SCALES.
WE'RE FORTUNATE THERE'S FEEDBACK
IN THAT PARTICULAR SCALE.
YOU CAN GET INSIGHTS AT EACH
SCALE AND BE LIKE OKAY IF YOU
COUPLE TO THE NEURONS IN THE
CORTEX WE SEE THIS PHENOMENA
THAT MAY EXPLAIN THE
OBSERVATIONS BECAUSE WE KNOW
WHEN YOU PERTURB PARAMETERS OF
STIMULATION THE COUPLING HAPPENS
AT THE INDIVIDUAL NEURON LEVEL
AND IF YOU CAN EXPLAIN SOMETHING
THERE IT CAN BUILD IN OTHER
MODELS.
AND I LIKE CONVERGING EVIDENCE
IN THE CONCEPT OF WE DON'T HAVE
ONE BIG MODEL THAT EXPLAINS
EVERYTHING MAYBE SOME TIME SOON
BUT THE EFFORT OF HAVING A LOT
OF MODELS AT DIFFERENT SCALES SO
NOT ONLY MULTI-SCALE BUT ALSO
PARALLEL EFFORTS WITH DIFFERENT
MODELLING APPROACHES SAY WHETHER
IT'S TRIPTOGRAPHY AND IF YOU
HAVE CONVERGING EVIDENCE, GREAT,
YOU'RE ON TO SOMETHING.
I ENCOURAGE AND MORE AND MORE
DATA IS AVAILABLE.
THAT'S A GREAT OPPORTUNITY FOR
MODELS AND WE CALL FOR MORE
INTEGRATION AND CONVERGENCE
GOING FORWARD.
>> THANKS.
THAT ALSO HIGHLIGHTS WHAT FOR
MANY OF US IS AN ITERATIVE
PROCESS AND LOOK AT THE DATA AND
SEE IF IT HOLDS UP AND RUN MORE
EXPERIMENTS AND GO BACK TO THE
MODEL AND KEEP REFINING TO SEE
IF THERE'S EMERGENT BEHAVIOR OR
NEW INSIGHT THAT CAN COME OUT OF
THAT PROCESS WHEN IT'S REALLY
TIGHTLY INTEGRATED TOGETHER.
THANKS.
IGNACIO.
>> THANK YOU.
I WANTED TO TALK ABOUT OUTSIDE
THE BRAIN AND WE'VE TALKED OF
NEURAL DYNAMICS AND THINGS THAT
HAPPEN WITHIN THE BRAIN AND THE
OTHER PART IS FOR THE MOST PART
HOW WE'LL BE VALIDATING THE
OUTCOME OF THE STIMULATION WHICH
IS BEHAVIOR AND TRANSLATIONAL
APPLICATIONS IN CLINICAL SCALES
AND SO ON, THIS IS SOMETHING
THAT OFTEN TIMES IT'S A BIT OF
AN AFTERTHOUGHT.
WE WANT TO DO THE DATA-DRIVEN
MODELLING OF THE CONSEQUENCE OF
STIMULATION IN THE END AND TRY
TO MAP THAT TO A SIMPLE CLINICAL
SCALE WITH LOW TEMPORAL
RESOLUTION IF ANY AND IT'S
REALLY DIFFICULT PROBLEM THAT
IMPEDES HOW WE'RE GOING TO BE
USING THESE THINGS AND IT IN
SOME ASPECT AND SOME CONTEXT IT
KIND OF DOESN'T MATTER HOW
SOPHISTICATED THE MODELLING IS
IF WE CAN'T IMPACT THE CLINICAL
SCORES.
THIS IS POTENTIALLY RELEVANT TO
SOME OF THE CONVERSATIONS WE'VE
HAD IN SESSION 2 YESTERDAY ABOUT
BEHAVIORS.
AND WE DO HAVE COMPUTATIONAL
MODELS OF BEHAVIOR AND USEFUL
SCALES SAYING WE CAN MAYBE MAP
ON TO THOSE OR DO CLINICAL
SCORES AND BETTER MAP THAT OUT.
SO THE IDEA OF ALGORITHMIC
TARGETING THINKING HOW THIS
PROCESSES ARE REPRESENTED IN THE
BRAIN AND MAYBE THAT'S WHAT WE
WANT TO MEASURE OR THE
SOPHISTICATION OF BEHAVIORAL AND
CLINICAL COMPLEXITY OF THESE
THINGS I THINK IS KIND OF A
DIFFERENT LAYER OF MODELLING
THAT I THINK WE SHOULD CONSIDER
AS A GROUP FUP.
HOW DO WE ESTIMATE THOSE AND HOW
DO WE MAP ON TO THOSE AND OFTEN
TIMES WE'RE GOING TO BE THINKING
ABOUT THOSE AS THE READ OUTS.
>> AND THOSE BEHAVIORAL READOUTS
ARE ACQUIRED AT DRAMATICALLY
TEMPORAL SCALES.
IT MAY BE ONCE A WEEK OR ONCE A
MONTH OR ONCE A DAY AND HOW DO
YOU CONNECT MODELS WORKING OVER
MILLISECONDS OR SECONDS OR
WHATEVER TIME SCALE TO THOSE.
THAT'S AN INTERESTING PROBLEM.
MIR
MIRIAM, DO YOU HAVE A COMMENT
ABOUT THAT?
>> I THINK THAT WAS A FANTASTIC
POINT IGNACIO RAISED AND A MAJOR
BOTTLENECK IN OUR MODELLING
BECAUSE OF THE SPARSE LABELS.
THIS IS THE CHALLENGE WE DEAL
WITH IN THE BRAIN DATA ANALYSIS
AND IT RAISES MULTIPLE
OPPORTUNITIES FOR RESEARCH.
ONE ENRICH THE MEASUREMENTS AND
THERE'S BEAUTIFUL WORK ON VIDEO
MONITORING, SPEECH,
PHYSIOLOGICAL MEASURES.
PERHAPS ALL OF THESE AT
DIFFERENT SCALES CAN ENRICH
BEHAVIORAL MEASURES BEYOND
SELF-REPORTS AND CLINICAL
ASSESSMENTS.
THAT'S ONE AREA OF BEHAVIORAL
MODELLING AND BEHAVIORAL
MEASUREMENTS THAT CAN ENRICH
THIS DIRECTION.
THE OTHER IS ON THE MACHINE
LEARNING SIDE.
FOR EXAMPLE, WE CAN THINK ABOUT
AGGREGATING DATA ACROSS PATIENTS
IN AN APPROPRIATE MANNER TO HAVE
MORE AND MORE BEHAVIORAL LABELS
IN THE MANNER DONE IN A.I. AND
THEN FINE TUNE TO AN INDIVIDUAL.
AND HAVE A RICHER AND LESS
SPARSE MEASURES.
THERE'S OTHER IDEAS IN THE
MODELLING SIDE TO ADDRESS THE
LABELS.
I THINK THERE'S OPPORTUNITY
PRECISELY RELATED TO THE
MODELLING AND SENSING SIDE THAT
WE COLLECTIVELY ALL SHOULD BE
THINKING ABOUT.
>> THANKS, PETRA.
>> THERE'S DIFFICULTY TO SEE IN
THE BACKGROUND BUT IT WAS NOT
SPOTTED SO I'LL GO TO VIKTOR
FIRST.
>> I MISSED IT.
>> DO YOU WANT TO SPEAK, VIKTOR?
>> NO, I TRIED TO CHANGE THE
COLOR BUT I DOESN'T WORK.
I WANT TO RESPOND TO CLAYTON AND
CHRIS WHEN YOU WERE TALKING
ABOUT THE DATA-DRIVEN MODELLING
BUT FITS WITH THE COMMENTS
IGNACIO MADE, SO FAR MOST OF THE
DISCUSSION WAS GOING AROUND AT
LEAST IMPLICITLY AROUND THE
TOPIC OF DATA MODELLING.
WE ARE MODELLING THE DATA WE
SEEK.
I'D LIKE TO INVITE A DIFFERENT
PERSPECTIVE.
I'LL TELL YOU WHY.
WHAT ARE MODELS?
THEY'RE COMPUTATIONAL
REPRESENTATIONS OF OUR KNOWLEDGE
AND WHAT WE BELIEVE AND THINK
COMMUNICATION HAPPENS HOI S ARE
WORKING, HOW DYNAMICS, EVOLVE,
ETCETERA.
THEY'RE A REPRESENTATION OF OUR
KNOWLEDGE.
THE DETAIL IS COMING FROM
KNOWLEDGE.
IT DEPENDS ON THE SCALE AND
CHOOSE A PARTICULAR SCALE.
AT SOME POINT THE MODELS GET
SEPARATED AND THE ADDITIONAL
DETAIL AND KNOWLEDGE WILL NOT
ADD THE PREDICTIVE POWER BECAUSE
IT WON'T IMPROVE THE PREDICTS.
HAVING SAID THIS, I WANT YOU TO
RECOGNIZE THE KNOWLEDGE SPACE
DESCRIBED BY OUR MODELS IS
TYPICALLY LARGER THAN THE DATA
SPACE.
WHAT I'M TRYING TO SAY IS THE
MODEL CAN BE TYPICAL OR LARGER
AND EXPLAIN THE PHENOMENA WE DO
NOT SEE IN THE DATA WITH MACHINE
LEARNING APPROACHES YOUR
ENTERING INTO THE DATA AND
TRYING TO EXTRACT THE STRUCTURE
IN THE DATA.
WHEN YOU LINK A CAUSAL MODEL --
A GENERATIVE MODEL TO DATA ONE
WAY OR ANOTHER SAY FOR INSTANCE
YOU ARE ACTUALLY ABLE TO MAKE
STATEMENTS THAT GO BEYOND THE
DATA SPACE.
I'LL GIVE AN EXAMPLE OUT OF OUR
OWN WORK WHERE WE WORK WITH
EPILEPSY.
BUILDING NETWORK MODELS THE WAY
PETRA, MAC VERY WELL DESCRIBED.
WE'RE MODELLING THE FULL BRAIN
NETWORK SPACE.
THE PATIENTS WE EXPLORE HAVE A
FINITE NUMBER OF ELECTRODES
IMPLANTED.
KNEES ARE THE DATA WE USE TO
BIAS THE MODELS AND MAKE
PREDICTIONS WHERE THE EPILEPTIC
ZONE IS.
WE'RE FINDING IT IN THE ONLY IN
THE PLACES SO THROUGH THE
PROCESS WHERE THE ELECTRONS WERE
LOCATED BUT OUTSIDE OF THIS.
AND THE PLACES NOT ACCESSIBLE TO
THE CLINICIANS.
WHEN YOU TEN THIS PUT THIS IN
RETROSPECTIVE DATA AND ANALYSIS
IT TURNS OUT THAT PREDICTIVE
POWER OF THE MODELS IS DIG
SIGNIFICANTLY BETTER THAN THE
ACTUAL CLINICAL DECISION MAKING
THAT WAS PERFORMED AND IN 30%,
29% OF ALL THE CASES THE
ADDITIONAL EPILEPTIC ZONES ARE
OUTSIDE OF THE AREAS THAT WERE
CLINICALLY ACCESSIBLE.
DUE TO THE MODEL AND SOMETHING
LIKE THIS YOU CAN ACCESS ONLY
WITH THE MODEL BECAUSE YOU
CANNOT MEASURE THERE.
SO THIS IS A POINT I WANTED TO
MAKE HERE AND MODEL IS A
FORMALIZATION OF OUR KNOWLEDGE
AND CAN BE MUCH VASTER THAN THE
DATA SPACE SO THE PROSPECTIVE IS
A MODEL DOES NOT ONLY EXPLAIN
THE DATA.
THE MODEL CAN GO WAY BEYOND THAT
AND TOGETHER USING THE MODELLING
AND DATA APPROACH WE WILL BE
ABLE TO MAKE PREDICTIONS THAT
CANNOT BE MADE WHEN WE WORK WITH
DATA ALONE OR WITH THE MODEL
ALONE.
SORRY THAT WAS LENGTHY.
>> I APPRECIATE IT AND A GREAT
ILLUSTRATION OF WHAT WE'RE
TRYING TO ACHIEVE, USING THEORY
AND MODELLING ALONG WITH
PHYSIOLOGICAL IS GREATER THEREIN
TE SUM OF ITS PARTS AND CAN
GENERATE NEW INSIGHTS.
ONE OF THE THINGS WE FOUND WE
HAVE TO BE VIGILANT ABOUT AND
PETRA TOUCHED ON THIS SPEAKING
AT THE BEGINNING OF THE SESSION
IS WHAT I CALL BY
OVERINTERPRETATION OF THE DATA.
WE MAID VISUALIZATIONS WE
THOUGHT WERE APPROPRIATE AND
CIRCUMSPECT AND UNINTENTIONALLY
PEOPLE WHO SAW THEM CAME TO
CONCLUSIONS THE MODELLING DID
NOT SUPPORT AND WE SAID HOLD ON
YOU'RE OVER INTERPRETING THIS OR
PUT A FEATURE IN THE
VISUALIZATION LEADING THE
INTERPRETATION ASTRAY.
WE NEED TO FIX THAT AND ADDRESS
THAT.
PETRA, I TOUCHED ON THIS IN YOUR
SLIDES WHEN YOU WERE TALKING
ABOUT GETTING THROUGH THE
PROCESS ALL THE WAY TO THE END
AND GOING THROUGH REGULATORY
PROCESSES AND MAKING SURE THAT
SYSTEMS USED NOT NECESSARILY IN
RESEARCH BUT IN CLINICAL
DECISION MAKING ARE WELL
DEFINED.
>> IF MAY GO TO WHAT VIKTOR SAID
FITS NICELY TO THE POINT I
WANTED TO MAKE AND ON YOUR
STATEMENT, VIKTOR, SO YOU WERE
SPEAKING OF A KNOWLEDGE SPACE
AND I DON'T KNOW HOW TO BEST
PRONOUNCE THE FIRST NAME BUT YOU
WERE MENTIONED WE HAVE A LOT OF
WORK TO DO AND START AT THE
GRAND SCALE AND DO OUR WORK ON
MODELS THAT EXPLAIN CERTAIN
OBSERVATIONS.
AND FILL UP THE KNOWLEDGE SPACE
THAT WAS DESCRIBED BY VIKTOR TWO
POINTS I WOULD LIKE TO MAKE.
THE FIRST POINT IS THAT NORD TO
ACHIEVE THIS WE NEED PROPER
ANNOTATIONS OF THE MODELS.
THERE'S MANY DIFFERENT KINDS OF
APPROACHES AND CAN BRING THEM
TOGETHER FOR THE BIOLOGICAL
MEANING OF THE ELEMENTS AND
POTENTIAL MAPPING OF THE
ELEMENTS WE CAN COMBINE AND WE
NEED NOT ONLY THE EXPERIMENTAL
DATA BUT NEED ALSO AN ANNOTATION
OF OUR COMPUTATIONAL MODELS TO
MAKE THEM ON TOP OF OTHER AND
THE SECOND THING IS I WOULD HAVE
MY DOUBTS ABOUT THE KNOWLEDGE
SPACE AND WE ONLY CAN LEARN WITH
TIME IF IT'S TRUE KNOWLEDGE IF
WE CANNOT QUANTIFY THE MODELS
AND KNOW IF THERE'S INFORMATION
OF THE MODEL THEORY.
IT'S STILL HYPOTHESIS AND
INTERESTING AND WHAT WE NEED.
WE NEED THEORIES OF PRINCIPLES
AND TRY TO FORTIFY AND IF WE
FAIL ON THAT, THAT MIGHT BE
TRUE.
>> IF THE COMMENT IS ON TOPIC,
WE SHOULD GO THERE FIRST.
>> OKAY.
>> GREAT POINTS WERE MADE.
I THINK THE DIFFERENTIATION
BETWEEN KNOWLEDGE AND DATA IS
SUPER IMPORTANT AND THEY OF
COURSE ARE RELATED.
WHEN YOU LOOK BACK AT THE
HISTORY OF PHYSICS WHERE THERE'S
A BASIC SUCCESSFUL EXAMPLE OF
GOING FROM DATA TO MODELS TO NEW
DATABASE AND THE MODELS AND THIS
WAS A SYNTHESIS OF EXPERIMENTAL
OBSERVATIONS AND THEY PRODUCED
NEW PREDICTIONS BECAUSE THERE
WAS A MODELLING STAGE AND THEN
THIS LED TO DISCOVERY OF
ELECTROMAGNETIC WAVES AND
EINSTEIN WENT FROM THAT TO THE
THEORY OF RELATIVELY AND ALL THE
NEW PREDICTS OF GRAVITY AND SO
ON.
IT'S CLEAR WE NEED DATA TO MAKE
MODELS AND BASED ON
GENERALIZATION OF THE MODEL AND
LEAD TO PREDICTIONS WE THEN HAVE
TO TEST WITH EXPERIMENTS AND
HAVE DATA AND KEEP BUILDING ON
THAT.
I WANTED TO CONSIDER THE ROLE
THAT FUNDING AGENCIES LIKE THE
NIH AND RESEARCH INSTITUTIONS
AND OF COURSE INDIVIDUAL
INVESTIGATORS PLAY IN THE BIG
QUESTION FOR AND DATA FOR THAT.
AND THIS SPEAKS TO THE FACT THAT
WE'RE EXPONENTIALLY PRODUCING
MORE DATA AND DATA CURATION AND
DATA STANDARDIZATION I THINK
IT'S EXTREMELY IMPORTANT.
I THINK THERE HAS TO BE MORE
INVESTMENT IN THAT BECAUSE IT IS
IT'S HARD FOR ME TO DO.
I THINK IT HAS TO BE MADE EASIER
BY DIFFERENT INSTITUTIONS AND
AMOUNT OF RESOURCES BY THE
EMPHASIS PLACED ON THAT AND BY
HOW MUCH THE INSTITUTION
PROVIDES PEOPLE WHO HELP WITH
THAT.
AND THAT'S HOW WE CAN GENERATE
KNOWLEDGE TO SYNTHESIZE MORE AND
MORE DATA AND THERE HAS TO BE
MORE EMPHASIS ON THAT.
AND THE AMOUNT OF PUBLICATIONS
IS EXPONENTIAL EXPLANATION OF
THE DATA IS PROLIFERATING.
THERE SHOULD BE INSTITUTIONAL
INVESTMENTS LIKE THE NIH
INVESTMENT IN USING THE GREAT
ADVANCEMENT IN MACHINE LEARNING
FOR LITERATURE AND WE HAVE
AMAZING DEVELOPMENTS IN THAT BUT
SPECIFICALLY HOW CAN WE EXTRACT
SCIENTIFIC KNOWLEDGE FROM THE
RESEARCH LITERATURE?
HOW CAN WE SYNTHESIZE PUB MED
INTO INSIGHTS TO TO HELP US
RATHER THAN PAPERS THAT CAME OUT
IN THE LAST WEEK.
THIS IS VERY IMPORTANT AND
EXTRACTING FROM THAT AND THERE'S
AN AREA OF INVESTMENT TO BE ABLE
TO CONVERGE THE DATA TO
KNOWLEDGE AND GENERATE MORE
HYPOTHESIS AND MORE DATA AND
MORE KNOWLEDGE AND SO ON.
WHEN YOU DO MODEL EXPERIMENTS IT
SHOULD BE DIFFERENT THAN WET LAB
EXPERIMENTS.
YOU KEEP A NOTEBOOK AND DO
EVERYTHING YOU DO AND ENDS UP
BEING THE METADATA THAT GUYS TO
YOUR EXPERIMENTS.
IT'S NOT JUST HAVING YOUR
VERSION CONTROL ON GITHUB.
IT'S KEEPING THE IDEAS YOU WERE
TESTING AND THE WAY THAT WAS
ENTERED INTO THE MODEL TO TEST
IT.
AND HAVE BETTER TOOLS TO DO THAT
IN A MORE AUTOMATED WAY.
CLAYTON?
>> WE HAVE ABOUT 10 MINUTES LEFT
AND WANT TO MAKE EVERYONE AWARE
AND PUT FORWARD ONE QUESTION
THAT'S ROUGHLY RELATED TO SOME
KIND OF CHAT DIALOGUE THAT'S
BEEN GOING ON AND ONE AREA OF
OPPORTUNITY FOR COORDINATED
EFFORTS AND MODELLING IN THAT
CONTEXT IS THINKING CRITICALLY
ABOUT HOW STRATEGIES FOR
INTEGRATING EXPERIMENTAL OR
EMPIRICAL INSIGHTS THAT UTILIZE
VARYING MODALITIES THAT WE DON'T
TYPICALLY THINK OF AS WE
GENERALLY STRUGGLE TO INTEGRATE
THE RESULTS, THE OUTCOMES OF
THOSE PERTURBATIONS.
I THINK IT WOULD BE USEFUL IF
THERE'S AGREEMENT TO TRY AND
ADDRESS THAT JUST FOR THE LAST
COUPLE OF MINUTES.
>> I DON'T KNOW IF THERE'S A
SILVER BULLET HERE.
I THINK IT'S REALLY HARD.
YOU HAVE TO WORK CAREFULLY WITH
PEOPLE SPENDING AND COLLECTING
THE DATA.
AND I WAS TRAINED TO DIFFERENT
TYPES OF MODALITIES USING THINGS
LIKE CALCIUM IMAGES, NEURAL
PICTURES AND WE TRIED TO
INTERROGATE DATA SETS FOR THE
EXPERTISE AND IT WAS MIND
BLOWING HOW MANY CHALLENGES
THERE ARE THAT ARE DIFFERENT AND
THE ONES WE DEAL WITH fMRI.
YOU CAN SAY WHATEVER YOU WANT
ABOUT fMRI BUT THAT FIELD HAS
BEEN THROUGH THE PRESSURE COOKER
IN TERMS OF BEING EXPOSED TO ALL
THE DIFFERENT CHALLENGES.
THE SOLUTION FOR US IN THE LONG
RUN WAS WORKING CLOSELY WITH THE
PEOPLE WHO COLLECTED THE DATA,
UNDERSTANDING WHAT KIND OF BUGS
AND FEATURES THEY SEE IN THE
DATA AND WHAT THEY CONSIDER
EFFECTIVE PROCESSING
TECHNOLOGIES, ETCETERA.
THAT UNDER SCORES A DIALOGUE
BETWEEN THE GROUPS IS CRITICAL.
A CRITICAL FEATURE IS WE CAN'T
DO IT ON OUR OWN AND HAVE TO
BRING PEOPLE WITH EXPERTISE
TOGETHER AND HAVE THEM FIND A
COORDINATED OUTCOME THEY WANT TO
WORK ON AND WORK TOGETHER TO
INVEST AND SOLVE.
IF YOU WANTED TO UNDERSTAND
CAUSAL PERTURBATION OF THE BRAIN
THAT'S HARD TO MEASURE WITH fMRI
I WOULD THINK OTHER SYSTEMS IS
IMPORTANT TO UNDERSTAND.
YOU NEED TO WORK WITH PEOPLE WHO
DO THE WORK DOWN AT THAT SCALE
AND UNDERSTAND THE CELLULAR
ARCHITECTURE OF THE SYSTEM AND
THEN YOU HAVE TO FIGURE OUT
PEOPLE TO STIMULATE THE SYSTEM
AND FIGURE OUT WHO CAN ANALYZE
THE DATA.
AND THERE ARE CAREERS WE NEED TO
EMBRACE THE MULTI-DOMAIN AND
INTERDISCIPLINARY AND THAT
SHOULD BE PART OF WHATEVER
SYSTEMS WE SET UP GOING FORWARD.
>> HAVE THOSE PEOPLE SIT NEXT TO
EACH OTHER FOR A WHILE LIKE A
FEW MONTHS OR YEARS.
AND UNINTENDED BENEFITS FROM
BEING CO-HOEKTED.
-- COLOCATED.
CLAYTON DID THAT ADDRESS YOUR
QUESTION OR HAVE FOLLOW-ON IDEAS
ABOUT THE TOPIC?
>> THAT WAS WONDERFUL.
>> IT'S A PERSISTENT CHALLENGE
FOR US TO FIGURE OUT HOW TO
INTEGRATE KNOWLEDGE FROM ALL
THESE DIFFERENT DOMAINS THAT
OFTEN HAVE DIFFERENT
VOCABULARIES FOR DESCRIBING IT
AND DIFFERENT MENTAL CONSTRUCTS
FOR HOW THEY THINK ABOUT AND
INTERPRET IT.
AND I DON'T KNOW ABOUT THE
PANELISTS BUT MY EXPERIENCE HAS
BEEN THAT IT WOULD BE RARE FOR A
COLLABORATOR OUTSIDE OF MY AREAS
OF EXPERTISE IN MODELLING TO
ADAPT THEIR BEHAVIOR TO THE
MODELS.
IT'S MORE LIKELY THAT WE NEED TO
ADAPT OUR KNOWLEDGE AND
VOCABULARY AND MODELS TO THE
PROBLEMS THE PHYSIOLOGICAL
PROBLEMS THEY'RE STUDYING.
OKAY, IN A LOT OF WAYS THAT'S
GREAT.
THAT'S WHERE WE WANT TO BE
HEADED BUT IT IS EXTRA WORK TO
LEARN HOW TO SPEAK THE LANGUAGE
AND TAKE THE TIME TO UNDERSTAND
THE DIFFERENT MENTAL CONSTRUCTS
THAT ARE SOMETIMES -- SO ACROSS
SCIENCE JUST SO BAKED IN BUT IT
CAN BE DIFFICULT FOR US TO
ARTICULATE WHAT THEY ARE.
IT'S SORT OF LIKE THE WAY WE
THINK.
ALL RIGHT.
WE HAVE A COUPLE MINUTE LEFT ANY
LAST QUESTIONS OR IDEAS FROM THE
PANEL?
PRETTY QUIET.
MAYBE I'LL TAKE A COUPLE MINUTES
AND WRAP UP.
FIRST I WANT TO THANK EVERYBODY.
THAT WAS GREAT QUESTIONS AND
DISCUSSION.
I REALLY ENJOYED IT AND I HOPE
WE KEPT IT PRACTICAL AND
GROUNDED ENOUGH FOR THE GENERAL
AUDIENCE.
AT THE BEGINNING I WAS SORT OF
TALKING ABOUT GETTING INTO SOME
ESOTERIC AREAS AND I THINK THERE
IS SOME DISCUSSION IN THE CHAT
ABOUT DEGENERACEY AND MAY BE TOO
DETAILED TO GET INTO THIS DURING
THE PANEL AS INTERESTING AS IT
IS.
AND WHY DO WE USE MODELS?
WE DO IT BECAUSE IT OFFERS US
SOME INSIGHT OR ADVANTAGE OR
UNDERSTANDING AND THAT
UNDERSTANDING DOESN'T NECESSARY
COME FROM THE FINAL RESULT.
IT GOES INTO THE PAPER.
IT COMES ALSO THROUGH THE
PROCESS OF STUDYING YOUR SYSTEM
AND LEARNING HOW IT BEHAVES AND
WATCHING IT AND TRYING TO TRAIN
IT.
AND SOMETIMES AND YOU HEAR AND
IT'S JUST THE OPPOSITE.
IT'S INSANELY DIFFICULT TO GET A
LOT OF THESE MODELS TO BEHAVE
THE WAY WE WANT THEM TO AND IN
BEHAVE IN WAYS THAT ARE
UNDERSTANDABLE.
OKAY, THANK YOU, EVERYONE.
THANK YOU FOR THE QUESTIONS AND
THE PARTICIPATION FROM THE
SPEAKERS AND THE DISCUSSIONANTS.
I REALLY APPRECIATE IT.
>> I CAN ALSO BRIEFLY THANK
EVERYONE AND FOR CHRIS AND THE
EFFORT AND DEEP THINKING HE'S
PUT INTO THE CONTENT OF THE
SESSION.
THANK YOU VERY MUCH.
>> THANK YOU.
>> THANK YOU, BYE-BYE.
>> I WANT TO ECHO THAT THANKS.
THAT WAS A FANTASTIC SESSION AND
THREW TO OUR SESSION 4 SPEAKERS
FOR THAT GREAT DISCUSSION.
NOW WE'LL MOVE INTO A BRIEF
RECAP OF THE WORKSHOP THUS FAR.
THIS RECAP IS INTENDED TO SET
THE STABLE -- STABLE FOR HOW WE
USE INVASIVE AND NON-INVASIVE
EFFORTS AND THERE WERE MANY
TOPICS ACROSS YESTERDAY AND THIS
MORNING.
SO MY SUMMARY WILL ONLY SCRATCH
THE SURFACE BUT A FULL RECORDING
OF THE MEETING WILL BE AVAILABLE
ON THAT NIH VIDEOCAST SYSTEM IN
THE NEAR FUTURE.
I'LL HIGHLIGHT SOME KEY THEMES
THAT EMERGED IN THE LAST DAY AND
A HALF.
YESTERDAY WE HEARD ABOUT
EXAMPLES OF PERTURBATION
APPROACH USED IN HUMANS AND
VALUE FOR PROVIDING EXPLANATION
OF COGNITION AND BEHAVIOR AT
DIFFERENT LEVEL.
AND UTILITY OF INTRACRANIAL EEG
AND NON-INVASIVE APPROACHES LIKE
ELECTROSTIMULATION AND NETWORKS
INVOLVED IN BEHAVIORAL FUNCTION
AND DYSFUNCTION.
FOLLOWED BY HOW THE APPROACHES
COULD BE USEFUL IN COORDINATED
EFFORT.
THERE WAS BROAD AGREEMENTS
THERE'S UNIQUE OPPORTUNITY SPACE
FOR MAPPING OUT BRAIN CIRCUITS
AND FUNCTION AND AGGREGATION CAN
BE IMPORTANT AMONG SPECIALIZED
GROUP AND DATA AGGREGATION COULD
BE NOT ONLY USEFUL BUT SOME
NEEDS IN THAT AREA IS IT COULD
BE BETTER SUPPORTED BY COMPLETE
METADATA AND SHARING OF RAW DATA
AND COMPLETE DATA SET AND COMMON
TOOLS FOR AGGREGATING DATA
ACROSS SITES.
AND THERE MAY BE OPPORTUNITIES
NOT JUST TO AGGREGATE DATA
WITHIN THE SPECIFIC MODALITIES
DISCUSSED BUT TO MERGE DATA FROM
DIFFERENT MODALITIES IN
SYSTEMATIC WAYS TO PROVIDE
CONVERGENT EVIDENCE AND INCREASE
THE CONFIDENCE IN OBSERVED
BEHAVIORAL RELATIONSHIPS AND
BECAUSE EACH HAVE THEIR OWN
NUANCES AND BIAS TO CREATE A
MORE WHOLISTIC PICTURE.
IT'S IMPORTANT TO COUNT FOR
VARIABILITY AND IN-PERSON
LOCALIZATION.
IT'S A TIMELY TOPIC IN LIGHT OF
SOPHISTICATED METHODS AVAILABLE
TO DEFINE VARIABILITY IN THE
FUNCTIONAL ARCHITECTURE OF BRAIN
NETWORKS AND REGIONS AND PROVIDE
OPPORTUNITIES TO UNDERSTAND
WHERE STIMULATION IS OCCURRING
AND HOW ITS AFFECTS MAY BE
PROPAGATING WITHIN INDIVIDUALS
AND DISCUSS QUESTIONS AND
CHALLENGES TO MEET THE NEED FOR
MORE STANDARDIZED WAYS OF
LOOKING AT THE
NEUROLOGICALESQUES OF
STIMULATION AND IMPORTANCE OF
CONSIDERING THE COMPLEX
PARAMETER SPACE THAT MAY BE
BEHAVIORALLY RELEVANT AND
DIFFERENT TYPES OF STIMULATION
HAVE DIFFERENT AFFECTS AND ARE
IMPORTANT TO CONSIDER ACUTELY
AND CHRONICALLY AND LOOK AT
EFFECTS ON LOCAL FUNCTION FROM
DISTRIBUTED INTERACTIVE NETWORK
FUNCTIONS.
AND OPPORTUNITIES AND CHALLENGES
THE PANEL DISCUSSED THE
IMPORTANCE NEUROETHICAL
PRINCIPLES THAT NEED TO BE
CONSIDERED AND THERE'S NO NEURAL
ETHICAL FRAMEWORK BUT CAREFUL
EXPECTATION OF WHAT IS STIMULATE
AND PATIENT CONSENT AND UNDER
THING THE EFFECTS OF STIMULATION
MAY HAVE DIVERSE EFFECTS ON
PEOPLE'S LIVES INSIDE AND
OUTSIDE THE CLINIC.
THE SECOND SESSION FOCUSSED ON
KEY CONSIDERATIONS FOR THE USE
OF BEHAVIORAL ASSESSMENTS.
OUR SPEAKERS OUTLINED A VARIETY
OF PARADIGMS ACROSS LEADING AND
LANGUAGE AND SOCIALISTIC
BEHAVIOR LOOKING AT STIMULATION
OF NETWORK NEURAL MODULATION AND
EEG RECORDINGS TO NAME A FEW.
THESE TALKS INFORM THE PANEL
DISCUSSION.
FIRSTLY IT'S IMPORTANT TO
UNDERSTAND HOW STIMULATION
DISRUPTS AND ENHANCED BEHAVIOR.
AND THAT ESPECIALLY IF ONE IS
TRYING TO SHIFT DYNAMICAL BRAIN
STATES EN ENHANCEMENT IT'S
IMPORTANT TO UNDERSTAND ONGOING
BRAIN ACTIVITY.
THEY DISCUSSED HOW THEY'RE
CHOSEN IN STIMULATION STUDIES
AND THERE'S CONCEPTUAL AND
PRACTICAL.
ONE IS CHOOSING THE RIGHT TO
PROBE THE NETWORK OF INTEREST
AND ANOTHER IS WHERE ELECTRODES
ARE PLACED CLINICALLY AND
THEORIZED BEHAVIORAL FUNCTIONS
OF THE REGIONS.
IN ADDITION, WHEN TASKS ARE
CONDUCTED IN THE CLINICAL
CONTEXT WHAT TASKS MIGHT PROVIDE
UNIQUE OPPORTUNITIES FOR STUDIES
IN HUMANS SUCH AS THOSE NOVELING
MOTION AND LANGUAGE AND THERE'S
OTHER PARADIGMS STUDYING NATURAL
BEHAVIORS AND UNIQUE VNKS AND
HELPING UNDERSTAND THE
MECHANISMS OF THE BEHAVIOR
ITSELF THERE COULD BE
OPPORTUNITIES TO UNDERSTAND HOW
LONGER TERM FLUCTUATIONS IN
SYSTEMS OVER HOURS OR DAYS
RELATES TO LONGER TERM
BEHAVIORAL OR SYSTEM VARIATION.
ADDITIONAL OPPORTUNITY IS PERM
PATIENT REPORT AFTER
STIMULATION.
SUCH AS FOCUS ON INTERNAL VERSUS
EXTERNAL STATE.
ANOTHER THEME WAS HOW BEHAVIORAL
APPROACHES CAN BE INTEGRATED AT
SCALE.
ARE THERE BEHAVIORS THAT CAN BE
AGREED UPON IN STANDARDIZED WAYS
OPPOSED TO IDIOSYNCRATIC
BEHAVIORS.
THIS MAY DEPEND ON THE LEVEL AT
WHICH WE WANT TO DRAW
INFERENCES.
IF THE GOAL IS TO UNDERSTAND
GENERAL BRAIN FUNCTION AND
STANDARD TASKS CAN BE USED WHERE
ALL CAN DO EQUALLY WELL WHEREAS
UNDERSTANDING VARIABILITY AMONG
PEOPLE AND THAT TASKS SHOULD BE
CHOSEN WITH MORE VARIABILITY AND
DATA ROUTINELY COLLECTED AS
CLINICAL CARE IS USABLE AND
SCALABLE ESPECIALLY WITH LEVEL
OF HARMONIZATION OR DATA
CURATION INVOLVED.
THE THIRD SESSION WAS DEDICATED
THE DISCUSSIONS OF THE LEVELS OF
EXPLANATION THAT CAN BE GAINED
FROM COORDINATED EFFORTS USING
PERTURBATION RECORDING AND
LEVELS OF EXPLANATION ACHIEVED
AND UNDERSTANDING THE
TOPOLOGICAL ARRANGEMENT USING
DEEP BRAIN STIMULATION AND HOW
IT CAN PROVIDE BIOMARKERS OF
DIRECT AND INDIRECT CONNECTIONS
AND ECOLOGICAL COMPUTATIONAL
PARADIGMS CAN BE USED BETWEEN
LEVELS OF UNDERSTANDING AND
TOPOLOGY CAN BETTER UNDERSTAND
DEPRESSION AND TRANSLATIONAL
IMPLICATIONS FOR THERAPEUTIC
NEURAL MODULATION.
THIS SETS THE STAGE FOR KEY
THEMES.
FIRSTLY, FOR PERTURBATION
STUDIES WHAT'S THE IMPORTANCE OF
UNDERSTANDING NEURAL DYNAMICS.
WHEN PERTURBING DYNAMICAL
SYSTEMS IT THE CHANGE OUT OF ITS
HOMEOSTATIC STATE AND SINCE IT
HAS IMPLICATIONS FOR
UNDERSTANDING MECHANISMS HOW CAN
IT BE ALIGNED BY ANATOMY AND
DYNAMICAL STATE AND HOW CAN WE
DO THIS AND HOW CAN THIS BE
INFORMED BY THE THEORETICAL
FRAMEWORKS.
THERE WAS DISCUSSION
TECHNOLOGIES THAT MAY BE INCLUDE
APPROACH LIKE CLOSE LOOP MAY BE
INFORMATIVE AND THE MODELLING
MIGHT DEPEND ON THE LEVELS OF
EXPLANATION BEING SOUGHT.
FOR ONE TRYING TO DEVELOP A
CLINICAL INTERVENTION AND
UNDERSTANDING DYNAMICS.
ANOTHER THEME WAS HOW TO ACHIEVE
THE LEVELS OF EXPLANATION TO
ACCOUNT FOR DIFFERENCES
FOLLOWING UP FROM THE
DISCUSSIONS NOTICE FIRST TWO
SESSIONS FURTHER DISCUSSION OF
NEWER TOOLS TO DO PRECISION
FUNCTIONAL MAPPING IN WITH LESS
AMOUNT OF CLINICAL DATA FOR
CLINICAL COHORTS WHICH COULD BE
USEFUL TO ALIGN INDIVIDUALS NOT
JUST BASED ON ANATOMY AND
UNDERSTAN
UNDERSTANDING INDIVIDUAL
RESPONSE AND STEPS THAT COULD
FACILITATE AND GENERATE
EXPLANATIONS WE ARE SEEKING.
THESE INCLUDE TASKS THAT ALIGN
WITH COMPUTATIONAL MODELS AND
DEVELOPING BETTER INFORMATICS
TOOLS TO ENHANCE MINING OF
STIMULATION DATA AND ACCESS TO
LARGER NUMBER OF INDIVIDUALS
ACROSS SITES AS WELL AS THE SAME
STIMULATION SITES ACROSS PEOPLE
AND ACCESS TO BETTER MANUALLY
CURATED CONNECTOME ANALYSIS TO
ALIGN WITH STIMULATION DATA.
IN THE FOURTH DATA WE HAD A NICE
DISCUSSION ABOUT HOW A THEORY OF
MODELLING CAN BEST BE INTEGRATED
WITH PERTURBATION AND I'LL
SUMMARIZE THE SESSION.
IN TERMS OF THERE WAS A NICE
DISCUSSION OF A VARIETY OF TYPES
OF MODELS BOTH DATA DRIVEN AND
PHYSIOLOGICALLY REALISTIC FROM
NETWORK CONTROL MODELS TO
MULTI-SCALE MODELS AND HOW THEY
CANNOT ONLY INFORM STIMULATION
APPROACH AND CLINICAL AND
NON-CLINICAL CONTEXT BUT ALSO TO
BRIDGE SCALES OF UNDERSTANDING
AND WHAT WE THINK WE KNOW ABOUT
THE BRAIN AND POTENTIALLY BE
ABLE TO PREDICT DYNAMICS AND
DATA BEYOND WHAT THE DATA MIGHT
REVEAL.
EXPERIMENTALLY AND HOW
COORDINATED EFFORTS WITH LARGER
SCALE AGGREGATION PLAY CREATE
DATA AT FINER SCALE AND ENABLE
VALIDATION IN A CAUSAL CONTEXT
AND ENRICH BEHAVIORAL MODELLING
ACROSS DOMAINS OF BEHAVIOR.
AND MAY BE HELPFUL IN DATA
COLLECTION THROUGH PROVIDING
SENSITIVITY ANALYSIS AROUND
VARIABLES THAT COULD BE
CHALLENGING TO FULLY EXPLORE
EXPERIMENTALLY.
THESE ARE NICELY OUTLINED
COORDINATED STIMULATION
RECORDING EFFORTS IN HUMANS.
THEY ALSO LAID THE FOUNDATION
FOR A DEEPER DIVE INTO PRACTICAL
CONSIDERATIONS NEEDED TO INFORM
SUCH COORDINATED EFFORTS.
AND SO AFTER THE BREAK WE'LL
TRANSITION TO PANEL DISCUSSIONS
FOCUSSED ON THIS AND SO EXAMPLES
OF TOPICS THAT MAY BE HELPFUL
FOR MORE IN DEPTH DISCUSSION
INCLUDE HOW AMENABLE THE VARIOUS
APPROACHES ARE TO
STANDARDIZATION ACROSS LABS.
WHAT EXPERIMENTAL PARADIGMS
FACILITATE EFFORTS AND ACCOUNT
FOR HETEROGENEITY IN THINGS LIKE
ELECTRODE PLACEMENT AND ACCOUNT
FOR DYNAMICS AND MEASURE.
THESE ARE A FEW EXAMPLES OF THE
TYPES OF QUESTIONS THAT MIGHT BE
FRUITFUL ONE IS ON INVASIVE AND
ANOTHER ON NONINVASIVE
APPROACHES AND SINCE THE TALKS
HAVE SET THE STAGE THE NEXT TWO
SESSIONS WILL HAVE A DISCUSSION
AMONG PANEL MEMBERS.
WE'RE LOOKING FORWARD TO THE
DISCUSSIONS AND WE'LL RETURN FOR
THESE SESSIONS AFTER THE BREAK.
SO WE WILL SEE YOU BACK AT 1:00
P.M. EASTERN TIME AND I JUST
WANT TO THANK AGAIN ALL OF OUR PANELISTS, THIS MORNING AND
YESTERDAY FOR SOME FANTASTIC, ENGAGING AND ILLUMINATING DISCUSSIONS.
THANKS SO MUCH. SEE YOU SOON.
>> THAT TRANSITIONS TO OUR NEXT
DISCUSSION AND NICE WAY TO KICK
OFF THE DISCUSSION.
WELCOME BACK EVERYONE FROM THE
BREAK.
I'M HAPPY TO INTRODUCE OUR FINAL
TWO SESSIONS CONSISTENT OF PANEL
DISCUSSIONS SURROUNDING THE
PRACTICAL CONSIDERATIONS NEEDED
TO INFORM COORDINATED RECORDING
EFFORTS IN HUMANS.
YOU CAN SEE OUR FIRST SESSION
WILL FOCUS ON EVASIVE APPROACHES
CHAIRED BY DR. SHETH AND MEGAN
FRANKOWSKI AND THE SECOND ON NON
INVASIVE APPROACHES BY JOEL VOS
AND ERIN QUINLAN.
IF YOU'RE A PANELIST FOR THE
FIRST SESSION ON THE LEFT IF YOU
CAN PLEASE NOW TURN YOUR CAMERA
ON.
WITH THAT JOIN ME IN WELCOMING
OUR CHAIRS, DR. FOX AND
DR. FRANKOWSKI AND I'LL TURN IT
OVER TO YOU.
>> THANKS A LOT.
I HAVE THE PLEASURE OF KICKING
OFF THE THIS FIRST OF TWO
PRACTICAL SESSIONS YESTERDAY AND
THIS MORNING FILLED WITH
INTERESTING DISCUSSIONS.
THE HOPE NOW IS TO SYNTHESIZE
PRACTICAL APPLICATIONS.
IT'S GREAT TO BE JOINED BY
DR. MICHAEL FOX WHO SPOKE
YESTERDAY AND MODERATED THE
FIRST SESSION YESTERDAY FROM
BRIGHAM AND MASS GENERAL AND
MEGAN FRANKOWSKI FROM NINDS AND
OUR PANELISTS ARE FANTASTIC AND
I WANT TO JUST OVER THE COURSE
OF A MINUTE OR TWO MENTION WHO
THEY ARE SO THAT EVERYONE CAN
PREPARE FOR ALL THEIR GREAT
REMARKS AND DIVERSITY OF
BACKGROUND THOUGHT, EXPERIENCE
ACROSS THIS QUESTION HOW TO
STIMULATE AND RECORD AND INFORM
UNDERSTANDING OF THE BASIS OF
PSYCHIATRIC DISORDERS.
WE HAVE THE NAMES HERE.
KARA JOHNSON WHO IS IN NEUROLOGY
AT UNIVERSITY IN FLORIDA AND HER
EXPERTISE IN NEURAL MODULATION
AND WE HAVE EXPERTISE IN BIO
ENGINEERING AND NEURAL
PHYSIOLOGICAL AND UNIVERSITY
FROM SUNSHINES IN NURSE SURGERY
AND BRINGING A PARTICULAR
BACKGROUND OF ENGINEERING AND
NEURAL DYNAMICS EXPERTISE AND
UNIVERSITY OF MINNESOTA WHO IS
AN EXPERT IN NEURAL
MONTHLYLATION OF MANY SORTS,
NEENKING AND PSYCHIATRIC
DISORDERS.
HELEN MAYBERG AT MOUNT SINAI IN
NEW YORK NEUROLOGY AND
PSYCHOLOGY AND EXPERIENCED
EXPERTISE IN THE NEURAL BASIS OF
DEPRESSION AND ITS TREATMENT
WITH A VARIETY OF TECHNIQUES AND
BRAIN CONNECTIVITY IN GENERAL.
STANFORD UNIVERSITY
REPRESENTATIVE WITH EXPERTISE IN
NEURAL MODULATION IN
NON-INVASIVE METHODS AND NEURAL
CIRCUITS.
>> DID WE LOSE SAMEER?
>> NO, I LOST MY POWER POINT.
ZOOM IS NEW TO ME.
WOE HAVE AN EXPERT IN BIOETHICS
AND DAMIEN FAIR WITH AN
EXPERTISE IN BRAIN RESEARCH WHO
IS REALLY AN EXPERT IN BAYESIAN
MODELLING AND MODELLING IN
GENERAL.
THERE'S A NUMBER OF TOPICS I
THINK WE CAN FOCUS THIS SESSION
ON DID A NICE JOB OF SUMMARIZING
THE FIRST DAY AND A HALF TO THIS
SESSION RIGHT BEFORE THE BREAK
AND I WANT TO PULL IN A COUPLE
THEMES FROM THAT AS WELL AS THE
DISCUSSION WE HAD AS A GROUP OF
PANELISTS A WEEK OR TWO AGO TO
JUST START FRAMING THE
DISCUSSION AND SUGGEST SOME
TOPICS TO FOCUS ON.
ONE IS THIS OPPORTUNITY ACROSS
ENVIRONMENTS SITUATION AND WE
TALKED ABOUT THIS IN THE FIRST
TWO SESSIONS YESTERDAY.
WHAT I MEAN BY THIS IS KIND OF
THE EVOLUTION AND AMALGAMATION
OF DIFFERENT ENVIRONMENTS WITHIN
WHICH WE CAN STUDY THE
RELATIONSHIP BETWEEN NEURAL
DYNAMICS, SYMPTOMS/BEHAVIORS AND
THE PERTURBATIONS AND CAUSAL
MANIPULATIONS WE CAN USE THE
ONLY WAY TO STUDY BRAIN DYNAMICS
TO DO RECORDINGS AND
PERTURBATIONS AND STIMULATION OF
LESION, ETCETERA.
THE WORLD OF THE INTRA-HOSPITAL
AND ENVIRONMENTS LIKE THAT HE'S
BEEN THE WORKHORSE AND WE RECORD
DIVERSE REGIONS OF THE BRAIN AND
PERHAPS IN A SELECTED TYPE OF
PATIENT POPULATION BASED UP
EPILEPSY AND TALKED ABOUT WAYS
TO MITIGATE POTENTIAL BIAS AND
MANIPULATE CIRCUITS FOR CAUSAL
INFLUENCE AND WE HAVE DEVICES TO
RECORD AS WELL AS STIMULATE QUE
CAN DO PERTURBATIONS AND WE CAN
FOCUS THE DISCUSSION OF HOW TO
BETTER DESIGN WHAT COMMON
ELEMENTS TO LOOK ACROSS STUDIES
THE MORE WE SINK KNOW
SYNCHRONIZE TO AGGREGATE DATA.
WE ARE FRAMING DISORDERS AND
CLUSTERS OF SYSTEMS AND IN OTHER
WAYS THERE'S MANIFESTATIONS OF
CIRCUITS GONE AWRY AND THAT'S
PERHAPS ONE OF THE MORE USEFUL
WAYS OF THINKING ABOUT THEM AND
WE TALKED ABOUT THIS IN THE
FIRST SESSION YESTERDAY.
HOW DO WE LOOK AT COMMONALITIES
ACROSS CIRCUITS AND
UNDERSTANDING SIMILARITIES AT A
CIRCUIT LEVEL BETWEEN DISORDERS
AND MODELLING WITH ACTUAL
COMPUTATIONAL AND QUANTITATIVE
METHODS.
HOW NECESSARY ARE BOTH OF THESE
AND HOW SUFFICIENT ARE EITHER OF
THESE.
ETHICAL CONSIDERATIONS.
BY THAT I DON'T NECESSARILY MEAN
TO DEFINE BY THE OPPOSITE OF
ETHICAL I DON'T THINK WE'RE
TALKING ETHICAL VERSUS UNETHICAL
BUT HOW TO BRING CAREGIVERS'
INTERESTS INTO THE CONVERSATION
IN A VERY INTENTIONAL WAY.
HOW MUCH ARE THE STUDIES AND ADD
TO THE BURDEN OF THE INDIVIDUALS
ALREADY DEALING TO HELP TREAT
AND HOW TO WE CONSIDER THEM
PARTNERS IN THE RESEARCH AND
BENEFICIARY FOR THE RESEARCH AND
PARTNERS IN DEVELOPING THE KIND
OF QUESTIONS WE WANT TO SPEND
AND STUDYING THINGS THAT ARE
MEANINGFUL.
ARE THEY ALSO OWNERS OF SOME OF
THE DATA AND THE PROPERTIES.
I'LL STOP WITH THAT.
WE'LL SEE IF THEY WANT TO ADD
COMMENTS IN TERMS OF FRAMING THE
DISCUSSION AND THEN OPENING IT
UP.
>> NO, BRILLIANT SET OF
QUESTIONS AND TOPICS AND AT THE
END OF THE WORKSHOP MOVING
TOWARDS PRACTICAL CONSIDERATIONS
AS WELL.
HOW DO WE BALANCE OUR WISH LIST
OF EVERYTHING WE MIGHT WANT TO
COLLECT WITH A MORE PRACTICAL
LIST OF WHAT MAY BE ACHIEVABLE
AT SCALE.
I CAN'T WAIT TO HEAR WHAT OUR
PANELISTS HAVE TO SAY ABOUT IT.
>> MEGAN, ANYTHING ELSE YOU WANT
TO ADD.
>> NOTHING ADDITIONAL I AGREE
WITH WHAT MICHAEL SAID AT THE
GLOBAL LEVEL OF WHAT WE CAN DO
TO GET AS MUCH AS THIS USE OF WE
CAN AND WHAT WOULD BE NEEDED
FROM AN ORGANIZATIONAL AND
INSTITUTION LEVEL AND RESEARCH,
RESOURCE LEVEL AND FUNDERS.
>> DOES ANYONE WANT TO START?
ALL RIGHT.
HOW WITH THIS ISSUE OF AND THIS
ISSUE OF THE DIFFERENT
ENVIRONMENTS TO BE HAD.
WE HAVE MINUTES TO HOURS AND
MINUTES TO TENS OF MINUTES AND
WITHIN THE MIDDLE OF A SURGICAL
PROCEDURE, FOR EXAMPLE, WE HAVE
HOURS AND DAYS IN AN IN-PATIENT
SETTING WITH INDIVIDUALS IN THE
EXAMPLE FOR SITUATIONS AND THEN
WE HAVE WEEKS AND MONTHS AND
YEARS IN INDIVIDUALS WHERE
INDIVIDUALS ARE LIVING THUR
LIVES.
HOW CAN WE DESIGN STUDIES TO
TAKE ADVANTAGE OF THESE
COMPLIMENTARY ABILITIES THAT WE
HAD ACROSS THE ENVIRONMENTS TO
LEARN SOMETHING MEANINGFUL?
BECAUSE IF YOU TAKE ANY
PARTICULAR DYSFUNCTION DISORDER
OR OPATHY WE HAVE TO UNDERSTAND
IT IN A WAY THAT MAKES SENSE
ACROSS THE TIME SCALE AND
DOESN'T DEPEND ON WHAT TIME
SCALE YOU LOOK AT.
THE DISORDER'S NOT CHANGING
BASED ON THE TEMPORAL LINES.
>> I WANT TO REFRAME IT A LITTLE
BIT OTHERWISE I THINK WE'LL ALL
CONTINUE TO NOT KNOW WHEN TO
JUMP IN.
I THINK WHAT I LEARNED FROM ALL
THE OTHER SESSIONS WAS IS YOUR
QUESTION HOW TO UNDERSTAND HOW
THE BRAIN WORKS AND THEN WE CAN
DISCUSS AT WHAT LEVEL OF
RESOLUTION BUT I'M GOING TO COME
IN FROM MY POINT OF VIEW IF WE
HAVE A CLINICAL PROBLEM AND WANT
TO SOLVE IT WE WANT TO KNOW HOW
IT WORK NOT JUST SO WE CAN DO
WHAT WE'RE DOING BETTER, IT WILL
LEAD TO UNDERSTANDING THE
DISEASE MODEL, IE, HOW THE BRAIN
WORKS BUT IT WILL ALSO
POTENTIALLY SCALE AND GENERALIZE
TO OTHER NEURAL MODULATION OR
NEURAL DEVICE INDICATIONS FOR
THE APPLICATION.
SINCE THERE'S A LOT OF PEOPLE ON
THIS THAT STUDY DEPRESSION,
THAT'S THE ONLY THING I KNOW
ABOUT, THAT THAT USE CASE KIND
OF COVERS THIS IDEA OF ALL THE
DIFFERENT LEVELS.
SO IN THE MOST INVASIVE SPACE
WHERE YOU HAVE THE MOST
OPPORTUNITY TO LEARN THE MOST
ABOUT THE BRAIN BUT ONLY FOR A
SORT PERIOD OF TIME.
THE NEW DEVICE ALSO LETS YOU GO
NOT QUITE AS GOOD ABOUT THE
BRAIN BUT YOU CAN COLLECT
INFORMATION ALL THE TIME LIKE
WITH THE SENSING SYSTEMS AND
WHAT IS PRACTICAL AND WHAT DO
YOU WANT TO KNOW AND HOW OFTEN
DO YOU COLLECT IT BECAUSE YOU
HAVE TO GET THE BUY-IN OF THE
COLLABORATOR, THE PATIENT, WHO
IS REALLY HAS INTEREST TO HAVE
THIS THING TO GET THEM BETTER.
BUT WHAT WE'RE CLEARLY LEARNING
IS THAT GETTING BEST IS
DIFFERENT AND WHAT YOU KNOW
ABOUT THE BRAIN IS DIFFERENT THE
LONGER YOU HAVE THE DEVICE.
SO IF YOU HAVE AN IMPLANTED
DEVICE IT'S A VERY DIFFERENT
SETTING OF THE TRAJECTORY OF
EXPERIMENT BECAUSE IT'S ACTUALLY
INDEFINITE.
IF YOU HAVE AN EXPERIMENT THAN
INTIMATE THE DESIGN IS
DIFFERENT.
I WANT IT MAKE SURE THAT'S THERE
ALONG THE CONTINUUM BECAUSE
FRANKLY THE PATIENT WILL
CONTINUE TO HELP YOU
INDEFINITELY IF THERE'S
SOMETHING IN IT FOR THEM AND
THAT MAY BE LESS ABOUT KNOWING
HOW THE BRAIN WORKS BUT INFORMED
OF HOW IT WORKS AND WHERE PEOPLE
CAN SHARE DATA BECAUSE DIFFERENT
PEOPLE WILL ENTER INTO THE
LINEAR DYNAMICAL SYSTEM GOING
FORWARD AT DIFFERENT EPICS.
SO IT MAY BE THAT NON-INVASIVE
MODULATION COMES CLOSE TO A
MODULATION STORY.
I CAN OFFER A SOLUTION BUT
WANTED TO FRAME IT I KNOW I'M
GOING TO THINK ABOUT THIS ENTIRE
DISCUSSION THROUGH THAT POINT OF
VIEW.
IT'S NOT ONE EXPERIMENT BUT
ONGOING SERIES OF EXPERIMENTS
AND PATIENT WILL HELP IF I THAT
SEEK IT'S ADDED VALUE FOR THEM
AND I'M HAPPY TO SHARE WHAT KIND
OF DATA PEOPLE ARE WILLING TO DO
AND WHETHER IT'S VALUABLE OR NOT
IN THE BIG PICTURE.
THANKS.
>> BUILDING OFF WHAT HELEN SAID
NOT EITHER/OR AND OUR COLLEAGUES
IN GENOMICS HAVE THE PROBLEM OF
HOW TO REASSEMBLE A COMPLETE
VIEW OF THE SYSTEM WHEN I KEEP
GETTING LITTLE FRAGMENTS.
WHAT DID THEY DO WHEN THEY
INVENTED SHOTGUN SEQUENCING AND
THEY INVENTED THE IDEA IF YOU
CAN FIND ENOUGH OVERLAP YOU CAN
EVENTUALLY BUILD THE COMPLETE
STORY.
SO I'M GLAD CORY HAS THEIR HAND
UP BECAUSE SOME OF THIS WORK IS
AN EXAMPLE OF THAT WE HAVE TWO
TECHNIQUES BEING USED TOGETHER.
WHAT WE DON'T DO WE DO AT fMRI
WORK OR DEVICE-BASED RECORDING
WORK BUT DON'T OFTEN HAVE THE
CASE WE DO BOTH SIMULTANEOUSLY
AND NO THE SAME SIGNAL LOOKS
LIKE DURING EEG AND ONBOARD
DEVICE AND THROUGH fMRI AT THE
SAME TIME.
NOW, OBVIOUSLY EACH ONE OF
THOSE -- LIKE DOING ONE MODALITY
AND WITH AN AND IS EXPONENTIALLY
HARDER AND A PLACE WHERE WE
WANTED TO UNDERSTAND WHAT EACH
CAN TELL TO ANOTHER.
THE WAY TO GET THERE.
>> YOU HAVE EXPERIMENTS THAT ARE
NOT CONTINUOUS ALL THE TIME.
WHAT DO YOU THINK ABOUT THIS?
>> IT COMES DOWN TO SCALES AND
WE HEARD FROM OUR MODELERS
FRIENDS AND WHEN WE THINK OF
TEMPORAL SCALES IN THE
LONGITUDINAL MONITORING, YOU CAN
ONLY DO SOME THINGS SO WELL.
SO YES, WE CAN MEASURE
INTRACRANIAL AND SCALP EDG AND
SOME LOOK AT LONGER TERM
LONGITUD
LONGITUDINAL MEASUREMENT AND WE
NEED TO ALIGN WITH COLLEAGUES TO
FOCUS ON OUR EXPERTISE AND BE IN
DISCUSSION WITH SPATIAL AND
TEMPORAL SCALE TO PUT THIS ALL
TOGETHER.
IT'S ALL VERY DIFFICULT.
AND SO WHEN WE THINK OF
INTRAOPERATIVE IT'S A DIFFERENT
SKILL SET THAN LOOKING AT
LONGITUDINAL MONITORING LIKE
HELEN DOES OVER MONTHS TO YEARS
AND IT'S HARD TO DO IT ALL
REALLY WELL.
ALL RIGHT, COOL POINT.
AND I THINK I'M NOT USED TO
SEEING A LOT OF GRANTS AND
PROJECTS LIKE THIS GROUP WILL DO
THE ACUTE AND PRODUCT THING AND
WE ALL ARE TRYING TO DO BOTH
IT'S LIKE A PARADIGM OF
COLLABORATION WHERE THE TIME
SCALES DIFFERENT.
IS THAT ONE THING YOU WERE
REFERRING TO?
OKAY.
>> WHAT I WAS GOING TO SAY IS
TRECH ALONG THE SAME LINES AS AC
EX AND CORY AND THINKING ABOUT
THE DIFFERENT ENVIRONMENTS AND
ACUTE VERSUS LONGITUDINAL IT
WOULD BE HELPFUL I THINK FOR A
LOT OF PEOPLE HERE AND WHO ARE
NOT HERE IF THERE WERE SOME SORT
OF GUIDANCES TO WHETHER WE CAN
ADD THINGS LIKE AN fMRI PROTOCOL
AND PATIENT ENROLLED IN A STUDY
AND THERE'S A LOT OF LOGISTICS
THAT GO INTO IT HIT BUT FOR
INSTANCE WE GET IMAGING ON EVERY
PATIENT WE DO DBS OR ESEG WE
WERE ALL DOING THE SAME THING
WITH THE PARAMETERS AND COULD BE
WE HAVE NON-INVASIVE PEOPLE
DOING TMS.
SHOULD THEY BE BUILT INTO
PROTOCOLS SOME EMS PROTOCOL.
THESE ARE THINGS IN THE
COLLABORATIVE SPIRIT SPECIALLY
DOABLE AND CAN BE USEFUL AND TOE
ADD TO THE SKUGS A DIFFERENT
PERSPECTIVE, I THINK THERE'S
BEEN SCIENTIFIC QUESTIONS AND
DESIGNING THE EXPERIMENTS BUT
THERE'S ALSO A MAJOR OPPORTUNITY
IN USING THE DATA THAT WE
COLLECT AS PART OF CLINICAL
CARE.
THAT'S WHAT WE FOCUSSED IN OUR
LAB AND THE INTRAOPERATIVE AND
HOSPITAL ENVIRONMENT OF USING
THE IMAGING AND
ELECTROPHYSIOLOGICAL RECORDINGS
AND DO TEST STIMULATION AND
RECORDINGS OF LFPs DURING THOSE.
THERE'S TONS OF DATA WE COLLECT
AND I'M SURE OTHER CENTERS
COLLECT AS WELL THAT COULD BE
POTENTIALLY AGGREGATED ACROSS
CENTERS.
THAT'S ONE ADVANTAGE I SUPPOSE
OF THE INTRAHOSPITAL ENVIRONMENT
IS WE HAVE A LOT OF DATA THAT
ALREADY EXISTS JUST THAT WE CAN
COLLECT DURING STANDARD OF CARE.
>> PERFECT, THANKS.
>> IT'S FUN HEARING THE
CONSENSUS AROUND THE IDEA OF
OPEN DATA AND DATA SHARING IN
THIS SPACE BECAUSE THIS IS A
CHALLENGE AND CULTURE CHANGE AND
BEFORE IT CAN BE REALIZED.
ON TOP OF JUST THE IDEA OF THE
DATA SHARING IS KIND OF TOOLS OF
INFORMATICS INFRASTRUCTURE TO
SET STANDARDS AND MAKE IT PEOPLE
TO SHARE DATA IS SOMETHING THAT
NOW IN NEURAL IMAGING IS
BECOMING MORE COMMON.
IN OTHER SPACES FOR LIKE NEURAL
PHYS AND OTHER DATA THAT MAY
COME OUT IT'S LESS.
AND THE REALITY IS LIKE THE DATA
BEING COLLECTED AND I'M GETTING
A REALITY CHECK BECAUSE WE'RE
LOOKING AT THE DATA IT'S
MASSIVE.
THE AMOUNT OF INFORMATION IS
HUGE.
THERE'S A WHOLE INFORMATICS
INFRASTRUCTURE THAT NEEDS TO BE
BUILT TO REALIZE THE IDEA OF
SHARING AND LEARNING FROM EACH
OTHER AND GRABBING PIECES OF
DATA FROM OTHER GROUPS AND ONCE
YOU HAVE THAT THEN THE POTENTIAL
ACCELERATES.
SO I LIKE THE DISCUSSION BUT
THERE'S THIS LAYER.
AND YOU NOTICE -- I DON'T KNOW
HOW MANY INFORMATICS PEOPLE ARE
ON THE CALL BUT THAT'S PROBABLY
ONE OF THE BOTTLENECKS TO BE
SOLVED TO MAKE THE REALITY OF
THE DATA SHARING COME TRUE.
>> YEAH, THAT'S SUPER IMPORTANT.
CLINICAL TRIALS, NINDS IS
IMPORTANT TO PLUG INTO THIS
EXAMPLE.
THE IDEA AND WE NEED A SIMILAR
INFRASTRUCTURE FOR AGGREGATING
AND STORING AND ANALYZING DATA.
IT WOULD ALLOW GROUPS THAT DON'T
HAVE THAT EXPERTISE TO PLUG INTO
IN ORDER TO MAKE THEM AVAILABLE
TO GROUPS.
>> THAT'S PART OF IT AND THE
OTHER PART IS THAT WHEN YOU ARE
SHARING THE DATA IT SITS ON TOP
OF A BASIC STANDARD TO THE BASIC
INFORMATION CAN BE AGGREGATED.
I USED TO MAKE A JOKE AND I HAVE
ALL THESE Ph.D.s AND POSTDOC AND
PEOPLE HAVE BEEN TRAINING FOR
THEIR ENTIRE CAREERS AND WHAT
THEY'RE DOING HALF THEIR TIME IS
FIGURING OUT HOW TO CONNECT THE
DATA ALL TOGETHER.
AND FUNDAMENTAL ASPECTS IF YOU
CAN GET THE CULTURE TO SHIFT YOU
WILL HAVE Ph.D.s DOING WORK.
THE INFRASTRUCTURE AND THE BASIC
STANDARDS IN CULTURE SHIFT AND
THEN ALL THIS CAN BECOME MUCH
MORE FEASIBLE.
>> IF I CAN PULL A THREAD FOR
ANOTHER ROUND, THERE ARE NIH
FUNDED DATA ARCHIVES RIGHT NOW
WHETHER AS THE GENOMICS OR OTHER
DATA.
I'M GUESSING THERE'S SOMETHING
THAT THEY'RE MISSING TO MAKE
THESE COMMENTS, RIGHT.
WHAT ARE THE ELEMENTS THAT WILL
WOULD HELP [INDISCERNIBLE].
>> PART OF THAT IS
STANDARDIZATION.
>> YEAH.
THAT'S RIGHT AND THE TOOLS TO BE
ABLE TO HANDLE -- WE'RE NOT
GOING TO BE NECESSARILY BUILDING
IT OURSELVES BUT IF SOMEONE HAS
TOOLS FOR THE MASSIVE DATA TYPES
OUT HERE BECAUSE WE CAN'T DO IT
OURSELVES.
THAT'S GOT TO BE SOMEBODY WITH
THE RIGHT TOOLS TO LEVERAGE FOR
THE PURPOSE.
>> THERE TO BE DATA TO BE USEFUL
ACROSS MODALITIES BUT IT'S
IMPORTANT FROM THE BEGINNING TO
FIGURE OUT HOW TO EXPLAIN THESE
THINGS IN A WAY THAT THE
PATIENTS CAN BECOME PARTNERS
AROUND IF WE'RE THINKING ABOUT
HAVING PATIENTS ALSO PROVIDING
DATA LONG-TERM THAT WE START
BUILDING THOSE RELATIONSHIPS
EARLY ON.
THEY ARE OFTEN TIMES UNDERGOING
CERTAIN CLINICAL PROCEDURES THAT
ARE IN THIS CASE WE'RE TALKING
ABOUT INVASIVE TECHNOLOGIES.
THESE ARE THINGS THAT WILL
THEY'VE BEEN TRYING MANY
DIFFERENT THINGS BEFORE THEY GET
TO A LOT OF THESE STUDIES.
IF WE'RE GOING TO DO A SERIES OF
EXPERIMENTS AND COLLECT DATA
LATER WE HAVE A WAY TO HELP
COMMUNICATE WHAT ARE EACH OF
THESE STUDIES HELPING PROVIDE
AND WHAT IS IT AS RESEARCHERS
WE'RE TRYING TO ACCOMPLISH AND
START WORKING FROM THE PATIENTS
FROM THE BEGINNING AND HELPING
UNDERSTAND THE EXPERIMENTS AND
HOW THEY CONTRIBUTE TO WHAT
WE'RE TRYING TO ACHIEVE.
>> I THINK WE'VE ALL SEEN AND
THIS IS A NEW THING SUBJECTS,
PATIENTS, PARTICIPANTS AND
CO-AUTHORS ON PAPERS EVEN PART
OF GRANTS.
CERTAIN PARTICIPANTS AND
WORKSHOPS.
OKAY.
>> MY EXPERIENCE IS ON DBS
STUDIES LONG TERM AND REQUIRE
EFFORTS FROM PATIENTS TO DO
RECORDINGS AND MONITOR THEIR
DEVICES.
WE NEED TO THINK HOW TO MAKE IT
WORTH IT FOR THE PATIENTS LONG
TERM AND SOME PATIENTS MAKE THIS
PART OF THEIR ROUTINE AND ONCE
THEY GET BETTER IT FALLS A PART
BUT IT'S THEY'RE BETTER BUT
THEY'RE NOT REALLY PARTICIPATING
IN THE RESEARCH AT THE SAME
LEVEL ANYMORE.
IT'S IMPORTANT TO CONSIDER
CHANGING THE PROTOCOL DEPENDING
ON THE CLINICAL STATUS OF THE
PATIENT BUT ALSO THINKING ABOUT
HOW DO WE MAKE THIS WORTH IT FOR
PATIENTS.
HOW MUCH DO WE COMPENSATE
PATIENTS FOR TIME AT HOME AND
FILLING OUT SELF-REPORT SURVEYS
AND DOING OTHER ACTIVITIES AT
HOME.
THEY'VE BEEN THINKING HOW TO
BACK UP OUR DATA IN A BETTER
WAY.
SO IN THE ENU WHEN YOU HAVE A
PATIENT FOR 10 DAYS AND THEN
DATA COLLECTION IS OVER YOU
DON'T GET MORE DATA YOU ZIP UP
THE FOLDER AND SEND IT TO THE
CLOUD OR BACKUP SERVICE BUT AT
THAT POINT IN THE NEW PATIENT
YOU MIGHT CONSIDER SHARING THE
DATA BUT IN DBS STUDIES WHEN THE
EXPERIMENT IS ESSENTIALLY
INDEFINITE AT WHAT POINT DO YOU
BACK IT UP?
AT WHAT POINT DO YOU SHARE IT.
AND A LOT OF THE DATA WE COLLECT
IS NOT EXACTLY A PART OF A
CLINICAL TRIAL PER SE, LIKE KARA
WAS SAYING WE RECORD ON TOP OF
ONGOING CLINICAL CARE.
WHAT ABOUT THE DATA SENT DON'T
HAVE A FIVE-YEAR, TWO-YEAR END
POINT AND HOW DO YOU SHARE THAT
AND ORGANIZE IT?
>> THE BRAIN SOMETHING ABOUT THE
BRAIN MAY HAVE TO CHANGE AND THE
WINDOW IS ONE HOUR AND YOU'LL
SEE SOMETHING BUT IF THAT HOUR
IS ONE OF MANY HOURS STREWN
ACROSS MONTHS AND YEARS OF
COURSE THE NEURAL CIRCUITRY IS
PRAS.
NOT CHANGING AND THE EXPERIMENT
IS ONGOING.
>> SORRY, I THOUGHT THERE WERE
OTHER PEOPLE BEFORE ME.
>> BACK TO THE DATA CRITICAL
GOING BACK TO THE RESOURCES AND
I THINK BACK TO THE CLINICAL
ISSUE OF WHAT DO YOU WANT TO
SAVE AND WHY?
I THINK THERE'S A HOARDING
PHENOMENON IF YOU COLLECT DATA
ARE YOU POINTING AT ME, ELLEN,
IT'S THE FEAR OF MISSING OUT.
WE ALL HAVE OCD AND NEED A
DEVICE FOR OUR OCD.
WE DESIGN AN IDEA AND KNOW WE
DON'T KNOW EVERYTHING AND ADD
MORE DATA.
WE'RE DROWNING IN DATA AND
CERTAIN THINGS WE INTRINSICALLY
KNOW IS ENOUGH.
WE KNOW FROM THE EXPERIENCE THE
MOST IMPORTANT DATA BUT THE
SCIENTIFIC MINDS SAY WE'RE
THOUGHT THAT SMART.
SOME SMARTER PERSON WILL LOOK AT
OUR DATA AND KNOW WHAT THEY
WOULD DO WITH OUR DATA.
I FEEL THAT WAY EVERY TIME I
LISTEN TO THE MODELERS.
THEY'LL COME UP WITH A NEW MODEL
IN AN UNSUPERVISED OR DATA
DRIVEN AWAY OPPOSED TO WHAT I
WANT TO SAVE.
IT'S CLEAN DATA SETS OF IMAGING.
I WANT A RULE BOOK THAT SAYS
COLLECT IT THIS WAY.
ENOUGH EXPERTS KNOW IT'S GOOD.
LIKE ABCD OR THE HUMAN
CONNECTOME DID.
I'M SURE THERE'S A BETTER WAY
BUT THAT'S A GOOD ENOUGH WAY AND
IF EVERYBODY AGREED TO I AGREE
ON SOMETHING UNDER THE SAME
DEVICE, THEN YOU GET MAYBE NOT
THE ONLY COMMON DATA ELEMENTS
BUT YOU GET SOME KEEPER COMMON
DATA ELEMENTS AND WHEN THERE'S A
SHARED EQUIPMENT EVERYBODY WOULD
LEARN IS IT HIGH ENOUGH
RESOLUTION, IS IT ACCURATE AND
PRECISE?
YOU LEARN IN WHAT DIRECTION TO
THROW IT ALL OUT AND START
TOTALLY OVER OR ITERATE AROUND
AND WE KEEP SAYING WE'LL COLLECT
IT THIS WAY AND NEVER GET TO
WHERE WE PICK SOMETHING WE ALL
AGREE TO DO EXCEPT THE HAMILTON
DEPRESSION RATING SCALE WHICH WE
KNOW DOESN'T GET AT WHAT WE WANT
EITHER.
THE OTHER THING IS I HAVE
PATIENTS WHO CONTINUE TO COLLECT
DATA EVERY DAY, TWICE A DAY,
BRING DATA, VIDEOS, WHY?
BECAUSE I'M GOING TO TAKE
SOMETHING AWAY FROM THEM?
NO.
THEY'RE HEARING THE GOAL IS AND
THEY'RE WORRIED.
CAN YOU HAVE A SIGNAL THAT WILL
TELL ME I'M GETTING INTO
TROUBLE?
NOT THAT JUST DOES SOMETHING
ALONE.
WHEN I FEEL BAD I CAN CHECK MY
DEVICE, MAYBE I KNOW WHAT IT IS.
WHAT DATA DO I NEED SO THAT
PATIENT HAS THAT AND COLLECT THE
DATA TO HELP US SOLVE IT.
OR WHAT'S A WAY TO KNOW THERE'S
AN ALARM AND ADVANCE BEFORE THEY
KNOW ANYTHING'S WRONG.
THEY'LL COLLECT THE DATA TO HELP
US KNOW THAT BECAUSE THAT MEANS
THEY WON'T KNOW.
THAT ALSO TELLS US HOW WE PUSH
THE FUNDERS, THE REGULATORS, THE
DEVICE BUILDERS TO BUILD US
STUFF THAT WE NEED WHETHER WE'VE
IDENTIFIED THINGS WE WANT.
SO THE PATIENTS DO TELL US WHY
THEY WANT THESE DEVICES OTHER
THAN MAKE ME WELL AND THAT
INFORMS THE DATA AND WE ALL
AGREE, YEAH, I DON'T THINK
THAT'S COOL AND I'LL GET A FIVE
ON MY INNOVATION LINE ON MY
GRANT AND THAT'S INFORMATION
EVERYBODY CAN SHARE AND BUILD A
MODEL AND THROW IT OUT OR SAVE
IT AND SOMEBODY SMARTER COMES IN
BUT JUST HAVING AN ORTHOGONAL
CONVERSATION FOR A WHILE AND
IT'S BECAUSE THE STRAIGHTFORWARD
THINGS WE FIGURED OUT AREN'T
COOL ENOUGH BUT CAN HELP SOLVE
THE PROBLEMS TO MAKE PATIENTS
COLLECT MORE DATA FOR US LATER.
>> THANKS, HELEN.
WES.
>> I CAN'T REMEMBER WHO SAID
THIS AT THE BEGINNING ABOUT
COLLECTING MULTIPLE MODALITIES
TO INFORM EACH OTHER AND THAT'S
DIFFICULT AND NOT MANY WILL DO
THIS.
THIS NOT MY FIELD SO A QUESTION.
WHAT ARE OTHER WAYS THE STUDIES
COULD BE DESIGN TO MAXIMALLY
INFORM AND NOT JUST A COLLECTION
OF STUDIES BUT DESIGN FEATURES
OR ELEMENTS OR DATA YOU COULD
COLLECT THAT COULD INFORM THE
DIFFERENT TYPES OF STUDIES
YOU'RE TALKING ABOUT.
THERE'S A LINE OF HANDS.
>> I RAISED MY REAL HAND AND GOT
PROMOTED TO THE FRONT OF THE
HINE.
IT ALIGNS WITH WHAT I WAS GOING
TO ASK TO MAKE PRACTICAL MOVES
FORWARD TOWARDS THIS COORDINATED
EFFORT AND THERE'S A LIMITLESS
NUMBER OF COOL SCIENTIFIC THINGS
WE COULD DO INCLUDING
MULTI-MODAL COLLECTIONS THAT
ALLOW US TO TRANSCEND DIFFERENT
LEVEL OF RECORDING AND
STIMULATION AND ANALYSES.
AND A HIGH HANGING FRUIT AND I
WAS STRUCK BY WHAT DAMIEN SAID
THERE ARE CERTAIN EXAMPLES WHERE
PEOPLE HAVE BEEN ABLE TO
STANDARDIZE PARAMETERS AND
COLLECTIONS AND GABRIEL'S POINT
ABOUT THESE ARE CLINICAL
PATIENTS AND WE HAVE TO REMEMBER
THERE'S COOL NEUROSCIENCE WE CAN
DO BUT THE PATIENTS THAT JUST
WANT TO GET BETTER.
I'M TRYING TO ORGANIZE PEOPLE'S
COMMENTS INTO ALMOST LOW-HANGING
FRUIT FOR A COORDINATED EFFORT.
THINGS CLOSE TO SOME TYPE OF
STANDARD WE CAN DO ACROSS
DIFFERENT SITES.
MAYBE IMAGING OR STIMULATION
SITE CLOSE TO THE LOW-HANGING
FRUIT AND ON THE CLINICAL SIDE
MAYBE THE LOW-HANGING FRUIT IS
THE STUFF WE CAN COLLECT
INVOLVED IN THE CARE IS THEIR
DEPRESSION OR PARKINSON'S
DISEASE SCORE GETTING BETTER AND
AT THE TOP OF THE FREE AN
ENDLESS NUMBER OF NEUROSCIENCE
THINGS WE CAN DO OR COLLECT AND
MAYBE THEY'RE HARDER TO
STANDARDIZE AND COLLECT IN A
COORDINATED WAY AND HARDER TO
STORE OR GET ETHICALLY BECAUSE
THEY'RE NOT DIRECTLY INVOLVED IN
THE CLINICAL CARE.
I THROW THAT OUT AS WE THINK HOW
WE MOVE TOWARDS THE COORDINATED
EFFORT.
>> AS A DIRECT COMMENT ON TO
THAT AND ADDING TO THE THINGS
HELEN WAS SAYING.
ONE DIFFERENCE BETWEEN HOW WE DO
NEURAL STIMULATION RESEARCH
RIGHT NOW AND YOU LOOK AT THE --
WHAT ARE THE MODELS FOR GRAND
PUBLIC DATA FOR UNDERSTANDING?
IT'S THE HUMAN GENOME PROJECT
AND NOW ALL OF US.
THOSE ARE SPECIFIC MODELS.
INVESTIGATORS WERE CONTRACTED TO
CREATE DATA FROM THE BEGINNING
FOR THE COMMUNITY.
THERE WAS AN UNDERSTANDING UP
FRONT THIS IS NOT
[AUDIO DIGITIZING]
IT'S FOR THE BROADER COMMUNITY.
WAS THE MODEL WHERE ALL OF US
RIGHT NOW ARE GENERATING DATA
AND EVEN THE MODEL VILL
INVESTIGATOR COLLECTS DATA TO
ANSWER THEIR OWN QUESTION AND
BOLTS ON STUFF THAT MAYBE WOULD
BE USEFUL DOWN THE ROAD.
THE CLOSEST ANALOGY WAS WHEN
THEY CALLED OFF A BUNCH AND YOU
CAN DO YOUR SMALL PIECE BUT
WE'RE ALL DOING THIS BIG THING
TOGETHER FOR THE BROADER THEME
OF LEARNING AND MEMORY.
IF WE WANTED A COLLECTIVE EFFORT
OF THE THAT'S HOW WE HAVE TO
THINK ABOUT IT FROM THE GROUND
UP WE AGREE WE'RE DOING THIS FOR
TOGETHERNESS NOT FOR OURSELVES.
>> WE DO ALL THESE COGNITIVE
TASKS IN EMU AND DIFFERENT
GROUPS HAVE DIFFERENT VERSIONS
OF TASKS AND HOW CAN WE
STANDARDIZE THAT.
IN AN IDEAL TASK I'D LIKE A TASK
REPOSITORY TO SEE WHAT CONSTRUCT
DO I WANT TO RUN AND DOWNLOAD
THE TASK FROM THERE.
I GET REQUESTS FROM MULTIPLE
PEOPLE, CAN YOU SHARE THE CODE.
WHY CAN'T WE HAVE THE CODE
SOMEWHERE.
IT'S ABOUT DATA SHARING AND
COMPARING RESULTS WITH ANOTHER
GROUP I DON'T KNOW IF WHAT I'M
SEEING IS A DIFFERENT TASK AND
WE SHOULD GO GROUND UP AND TRY
TO CREATE A COGNITIVE TASK WHICH
IS I WOULDN'T SAY EASIER BUT
MORE APPROACHABLE THAN THINKING
OF SHARING DATA IN THE FIRST
PLACE.
THE SAME APPLIES FOR WHEN WE
MOVE FROM IN-HOSPITAL TO THE
WILD, FOR EXAMPLE.
HOW DO WE TRANSLATE THE
COGNITIVE TASKS WE PERFORM IN A
CONTROLLED ENVIRONMENT INTO LIKE
A FREE ENVIRONMENT HOW DO THESE
MATCH UP OR IF I'M DOING A
COGNITIVE TASK IN THIS
ENVIRONMENT HOW WOULD THAT
TRANSLATE?
THESE ARE SOME BASIC QUESTIONS
THAT WE FIRST NEED TO FIGURE OUT
EVEN BEFORE WE TAKE OFF THE DATA
THAT'S RESULTING FROM IT.
>> I THINK YOU HIT A NERVE ZOOM
IS BUBBLING UP ALL KINDS OF
ICONS AND NOW THERE'S FOUR TIMES
AS MANY HANDS AS BEFORE.
YOU'RE TALKING ABOUT
REPOSITORIES OF TASK AND CODE
>> A REPOSITORY AND I NEED A
TASK TO LOOK INTO COGNITIVE
CONTROL OR WORKING MEMORY AND I
KNOW ANOTHER GROUP USED THAT AND
CAN COMPARE RESULTS WITH THEM.
>> COULD THAT BE SIMILAR TO THE
NIH TOOLBOX FOR TASK-BASED --
>> YEAH.
THERE'S EVEN CODING THE TASKS AS
EVERYBODY USES A DIFFERENT CODE.
IF SOMEBODY HAS ALREADY CODED
IT, I DON'T THINK ANOTHER GROUP
SHOULD WASTE TIME TRYING TO CODE
THE SAME TASK.
>> WE CAN USE THE EXISTING
INFRASTRUCTURE IN A NEW USEFUL
WAY.
>> BROWN WERE TRYING TO GO
TOWARDS THAT AIM AND I THINK OF
SOMETHING LIKE THAT WOULD BE
HUGELY USEFUL
>> I WAS INVOLVED WITH BROWN HAS
A VERY NICE CENTER FOR COMPUTING
AND VISUALIZATION.
THE CCCV.
WE WERE WORKING WITH THEM TO
CREATE BEHAVIORAL TASKS THAT
WERE LIKE DEPLOYED AND
EXECUTABLE TO BE EASILY
INSTALLED IN MULTIPLE LOCATIONS
AND SHARE COLLABORATORS.
YOU DON'T NEED A SPECIFIC
VERSION OF LAB RUNNING THAT'S
ABLE TO PLAY NICELY WITH THE
TOOLBOX AND LEADS TO WHEN YOU'RE
RUNNING THE TASK AND DON'T HAVE
TECHNICAL EXPERTISE TO DEBUG ON
SITE.
I THINK ONE OF THE THINGS I
THINK SHE WAS GETTING AT WAS
STANDARDIZING DATA COLLECTION.
THAT'S IMPORTANT LIKE EVEN WHEN
I SHARE MY DATA IT REQUIRES
CONVERSATIONS.
SO I THINK THAT STANDARDIZING
COLLECTION IS IMPORTANT.
ANOTHER THING A COUPLE THINGS
PEOPLE HAVE TOUCHED ON IS HOW DO
WE UNIFY THE DIFFERENT MODALS.
IF WE COLLECT DAIT ACROSS
DIFFERENT MODALITIES I FEEL LIKE
THEY'RE SILOED.
YOU PUBLISH PAPER AND WE NEED TO
BE LIKE INTEGRATING THINGS MORE
AND I THINK LIKE A GOOD WAY TO
DO THAT WOULD BE TRYING TO
FIGURE OUT WHAT IS THE
OVERARCHING HYPOTHESIS THEY CAN
HAVE ACROSS ALL THESE MODALITIES
AND HOW DO YOU INTEGRATE EACH
ONE.
ANOTHER THING HILLELEN SAID THE
SHARING THE DATA AND PEOPLE LIKE
WEARABLES BECAUSE IT'S FUN TO
SEE THE DATA AND I THINK IF WE
COULD THINK ABOUT LIKE HOW MUCH
YOU'RE SLEEPING AT NIGHT OR HOW
STRESSED ARE YOU OVER TIME?
THOSE ARE THINGS APPLE WATCH CAN
TELL YOU AND IF WE CAN GIVE THE
DATA BACK TO INFORM PATIENTS IT
MAY BECOME MORE OF A SYNTHESIS.
>> I WARRANT TO -- WANT IT MAKE
ONE COMMENT IN BETWEEN TO
FOLLOW-UP ON AND MAYBE GABE WHEN
WE GET TO YOUR HAND AND TALKING
ABOUT OCD PATIENTS AND SAY WE'RE
DOING THIS IN PATIENTS WITH PD.
THERE'S A BIG DIFFERENCE IN TERM
OF HOW THAT PATIENT HAS A
DISCUSSION ABOUT GETTING DBS OR
WHATEVER INVASIVE NEURAL
STIMULATION AND A DIFFERENT
CONVERSATION WITH DEPRESSION
WITH TE STATE OF THERAPY AND
ROLE OF RESEARCH AND THEY KNOW
IT'S INVESTIGATIONAL AND
PARTICIPATING IN A RESEARCH
MISSION.
THAT PLAYS A BIG ROLE.
I THINK THAT PLAYS A BIG ROLE IN
TERM OF ENGAGEMENT OF THE
RESEARCH AND MAY MOTIVATE IN
DIFFERENT WAYS TO PARTICIPATE OR
NOT OVER THE COURSE OF TIME.
ULTIMATELY THESE PEOPLE WANT TO
GET BETTER AND AFFECT THEIR
LIVES WITHOUT TALKING TO US AND
THAT'S TRUE WITH SOME
INDIVIDUALS AND MAYBE NOT
OTHERS.
THERE'S A BIG LOAD STATE OF
THERAPY PLAYS IN THIS.
WES.
>> I'LL CONNECT A FEW LINES I
THINK WOULD HELP FOR THAT.
SO, WE CAN DO THAT AND EVERYBODY
TAKE A TURN AND WHEN IT'S YOUR
TURN, PLEASE DO YOUR COMMENT AND
ADD TO THAT.
>> FLIES OTHER SOURCES OF
VARIATION BETWEEN STORAGE AND
COLLECTION AND PERSONAL-LEVEL
VARIABLES AND GETTING A
COMPREHENSIVE LIST OF WHAT THE
VARIABLES CAN BE SO PEOPLE CAN
ACCOUNT FOR SOURCES OF VARIATION
ACROSS MEASURING VARIABLES
OPPOSED TO WONDERING DIFFERENT
CIRCUMSTANCES.
>> THERE'S STANDARDIZED
BEHAVIORAL TASKS ACROSS SITES.
IT SOUNDS LIKE A GOOD IDEA.
IT SEEMS LIKE IT WOULD BE USEFUL
AND EASY TO IMPLEMENT AND IT'S
INCREDIBLY DIFFICULT TO
STANDARDIZE COGNITIVE TASKS TO
ENSURE UNIFORM PERFORMANCE
ACROSS SITES.
IT REQUIRES A LOT OF TRAINING
AROUND CARE AND CONSIDERATION
AND CAN GO POORLY AND LEAD TO
JUNK IN, JUNK OUT KIND OF
PROBLEMS IF YOU DON'T HAVE GOOD
STANDARD AND PROCESSES CONTROL
SET IN.
SAME THING APPLIES TO THE KIND
OF DATA WE'RE TALKING ABOUT
SHARING AND WONDERING IF YOU
GUYS ARE GOING TO GET INTO HOW
YOU ENSURE THAT KIND OF
STANDARDIZATION AND QUALITY IN
INTERCRANIAL STIMULATIONS AN
RECORDINGS AND IF THERE'S
SPECIFIC FACTORS YOU HAVE TO
ACCOUNT FOR MAKING SURE YOUR
STIMULATION IS GETTING IN THE
BRAIN AND HOW DO YOU VALIDATE
THAT AND MAKE SURE IT'S STANDARD
USED ACROSS SITES AND WONDER IF
THAT TOPIC HAS COME UP AT ALL.
>> THERE'S A LOT OF DETAIL YOU
MENTIONED AS WELL.
IF YOU'RE NOT COLLECTING IT
YOURSELF AND HAVEN'T SEEN THE
PATIENT DO IT, WHAT ARE YOU
MISSING IN TERMS OF SOMATIC
INFORMATION
>> I WANT TO MAKE A QUICK PLUG
WHAT WITH WAS SAID.
GOOD DATA SHARING COMES WHEN
THERE'S FUNDING INVOLVED AND THE
RAM PROJECT AND THERE'S THE
INVESTIGATOR DRIVEN SUBMIT TO
NDA WITH THE COUPLE THOUSAND
DOLLARS ALLOCATED ON THE BUDGET.
THAT DOESN'T WORK AS WELL AS
WE'VE SEEN.
I'M WONDERING IF THERE'S
SOMETHING IN BETWEEN THAT IF
THERE'S A SUPPLEMENTAL FUNDING
TO PROVIDE A PERCENTAGE OF RA
TIME THAT SPANS ACROSS PROJECTS
THAT IF WE'RE TALKING ABOUT
INNOVATIVE STIMULATION AND
RECORDING WE'RE LOOKING AT
SINGLE PULSE RESPONSES AND I
REACH OUT TO HELEN AND SAMEER
AND OTHER WHO HAVE THEIR OWN
FUNDED GRANTS AND THERE'S A
SUPPLEMENT ALLOWED TO COLLECT
DATA IN A STANDARDIZED WAY AND
SHARE THAT DATA IN A
STANDARDIZED WAY AND THAT WOULD
BE VALUABLE I THINK TO THE
COMMUNITY AND WE COULD STILL DO
OUR OWN PROJECTS AND OUR OWN
WORK BUT COLLABORATE TOGETHER TO
MAKE SURE THAT THOSE ARE
COLLECTED IN A STANDARDIZED WAY.
I DON'T KNOW IF THAT'S POSSIBLE
OR EXISTS BUT I THOUGHT IT WAS
INTERESTING.
>> THANKS, CORY.
DAMIEN.
>> THERE'S AN EDUCATION
COMPONENT TO THE STATE OF
AFFAIRS OF THESE KINDS OF
INVASIVE TECHNIQUES AND FOR
TREATING PATIENTS AND LEARNING
NEUROSCIENCE.
WE'RE NOTICING A LOT OF TIMES
PARTICULARLY IN THIS SPACE IT'S
ALWAYS PATIENTS AND A LOT OF
TIMES FOLKS EVEN CLINICIANS AND
PRIMARY CARE AND OTHERS NOT AT
ADVANCED CENTERS IN THE WEEDS
FEEL LIKE A LOT OF THE
EXPERIMENTS ARE THE COWBOYS
GOING IN AND POKING BRAINS AND
THINGS WITHOUT A PROPER
EDUCATION WHERE THINGS ARE AT
TODAY BECAUSE I FEEL THE
ADVANCEMENTS ARE HIGH TO DO
GREAT THINGS.
MAYBE BUTTRESSED BY NOT HAVING
PROPER EDUCATION IN THE MEDICAL
ARENA AND OUTSIDE OUR IMMEDIATE
SPHERES WE COLLABORATE WITH AND
A TOPIC I THOUGHT I'D THROW OUT
THERE.
>> I WONDER IF ANOTHER PART OF
THIS MENTIONED IS A HIGH START
UP COST FOR GETTING INTO THIS
BUSINESS.
AND YOU CAN COLLABORATE AND
THERE'S CROSS-VALUE FOR
EDUCATION AND HOW TO DO THIS AND
HOW TO CONTRIBUTE ERN A
MEANINGFUL WAY.
>> I WANTED TO BRING UP THE
IMPORTANCE OF HELPING
RESEARCHERS UNDERSTAND NOT JUST
THE RESEARCHERS HERE BUT
UNDERSTAND THE UTILITY OF
SHARING DATA AND HOW CAN YOU
ACTUALLY PROMOTE PROGRESS AND
HOW DOES THIS ACTUALLY WORK?
SO IF THERE'S SOME KIND OF
PROGRAM AS WAS DISCUSSED BEFORE,
SOMETHING THAT WHERE YOU CAN
DEVELOP AN A DEAL MODEL AND TRY
THIS WITH RESEARCH GROUPS AND IT
WILL TAKE TIME BUT THEN PEOPLE
COULD SEE A FEW YEARS DOWN THE
LINE LIKE WHAT WAS THIS MODEL OR
PROGRAM ABLE TO ACHIEVE BY
WORKING TOGETHER AND BRINGING
TOGETHER ALL THE DIFFERENT
MODALITIES.
I THINK THAT WOULD REALLY HELP
RESEARCHERS FOR EXAMPLE IN
GENOMICS, YES, INSIDE GENETICS,
FOR EXAMPLE, WASN'T UNTIL YOU
START BRINGING TOGETHER ALL
THESE DIFFERENT SAMPLES THAT
PEOPLE START MAKING PROGRESS AND
IDENTIFYING GENOMIC LOCI AND THE
STUDIES TEND TO BE INVASIVE
NEURAL TYPE STUDIES TEND TO BE
RELATIVELY SMALL.
IT ALSO TAKES TIME TO BE ABLE TO
SAY SOMETHING MEANINGFUL ABOUT
THE EFFECTIVENESS OR SAFETY OF
THE DEVICES.
AND EXPLAIN THE UTILITY OF IT
WOULD BE CRITICAL.
>> DO YOU HAVE ANYTHING ABOUT
THE PATIENT POPULATION AND
THERAPY WHERE SOMEONE IS 99.9%
THERE TO GET BETTER.
>> ALTRUISM COMES UP REGARDLESS
OF THE TYPE OF PATIENT.
SO YOU THINK THERE'S A LOT OF --
WELL, FOR MANY OF THESE
PARTICIPANTS THEY OBVIOUSLY HAVE
EXPERIENCE AS A SEVERE CONDITION
FOR QUITE A LONG TIME.
AND SO THERE IS AN AFFINITY AND
SOME EMPATHY THEY WANT TO BE
ABLE TO HELP OTHERS WHO MAY BE
IN A SIMILAR SITUATION.
SO IN THAT SENSE, EVEN IF SOME
PARTICIPANTS ARE MOTIVATED
PERHAPS BECAUSE THEY KNOW THAT
FOR EXAMPLE DBS FOR DIFFERENT
MOVEMENT DISORDERS IS MORE
ADVANCED THAN DBS FOR SOME
PSYCHIATRIC DISORDERS.
THERE'S STILL THAT ALTRUISM AND
SIMILAR TO UTILITY WITH
RESEARCHERS.
IF WE CAN HELP THE PATIENTS ALSO
SEE WHAT THE UTILITY IS FOR THE
FIELD FOR ADVANCING THE SCIENCE
AROUND AS HELEN WAS SAYING, IF
THERE'S SOME KIND OF UTILITY YOU
CAN ALSO IDENTIFY FOR THE
PATIENTS THEMSELVES THAT WILL
GET YOU A LONG WAY BECAUSE THESE
ARE PEOPLE THAT OFTEN WANT TO BE
ABLE TO HELP AND MAKE MEANING
FROM THEIR EXPERIENCE AND HELP
OTHERS THAT HAVE HAD SIMILAR
EXPERIENCES.
YOU
>> LET ME ALL ASK YOU ONE MORE
PRACTICAL DISCUSSION.
WHAT DO YOU THINK ABOUT THE IDEA
OF PAYMENT COMPENSATION FOR
PATIENT PARTICIPANTS WHETHER
IT'S ACUTELY IN THE O.R. OVER
LONG PERIOD OF TIME, COERCION,
UNDUE INFLUENCE.
ARE THESE FACTORS AT ALL.
SHOULD THEY BE PAID, NEVER BE
PAID?
WHAT COMPENSATION IS REASONABLE?
IS IT ALL ALTRUISM?
HOW MUCH IS THE MINIMUM OR TOO
MUCH?
NOT TO PUT YOU ON THE SPOT.
>> OKAY.
SO I THINK ONE IMPORTANT PART
AND AS YOU KNOW LIKE MANY OF THE
PATIENTS WHO PARTICIPATE IN THE
TRIALS MAY NOT BE FROM AROUND
THE AREAS WHERE THESE CLINICS
ARE LOCATED.
SO THERE ARE DIFFERENT COSTS
ASSOCIATED WITH PARTICIPATING
THAT I THINK IT'S VERY IMPORTANT
TO HELP THEM COVER THOSE COSTS.
BUT TO THE EXTENT THAT SOME
COMPENSATION CAN HELP DEFRAY
SOME COSTS ASSOCIATED WITH
PARTICIPATING WE KNOW OFTEN
THESE ARE PATIENTS THAT MAY HAVE
HAD DIFFICULTIES MAINTAINING A
JOB OR WORKING AT THE LEVEL THEY
WOULD LIKE TO BE WORKING BECAUSE
OF THE TYPE OF CONDITION.
IT COULD BE HELPFUL BUT A
CONVERSATION THAT WOULD REQUIRE
A LONGER DISCUSSION TO EXPLORE
WHAT WOULD BE HELPFUL.
>> YEAH.
IT'S TOUGH.
YOU THINK WE CAN AGREE THERE
COULD BE TOO MUCH AND A VERSION
THAT IS TOO MUCH.
NOT ENOUGH WOULD BE WHERE A LOT
OF US HAVE BEEN FOR SOME TIME.
AND THIS QUESTION IS IS THERE A
GOLDILOCKS POINT AND I WOULD
HAZARD FOR A LOT OF THESE THINGS
IT'S PROBABLY ZERO BUT THERE'S A
LOT TO DISCUSS.
ANYWAY, BACK TO THE MAIN THEME,
KARA.
IS THIS ABOUT A QUESTION I HAD
FOR YOU?
>> YES, IT IS.
A QUESTION YOU ASKED A WHILE AGO
NOW.
BUT NICELY PIGGY BACKS AND
SAYING ABOUT DIFFERENT PATIENT
POPULATIONS.
A LOT OF OUR EXPERIENCE LATELY
HAS BEEN WITH PARKINSON'S
DISEASE PATIENTS WHICH WE KNOW
ARE OLDER AND ARE OFTEN
UNDERGOING ARE DBS BECAUSE OF
VERY SIGNIFICANT DISABILITIES
THERE'S PARTICIPATION UP
RESEARCH GROUP AND ONE REASON IS
ABILITY TO PARTICIPATE IN THE
RESEARCH AS WE MOVE MORE TO THE
CHRONIC RECORDING DOMAIN.
WE WANT TO BE ABLE TO USE
AUTOMATED OR SEMI-AUTOMATED
METHODS AS MUCH POSSIBLE TO
REDUCE BURDEN BUT COMES WITH THE
NEED FOR TECHNOLOGY SAVVY AND
WITH AN OLDER POPULATION A LOT
OF THIS BURDEN CAN FALL ON THE
CARE PARTNER.
SO THAT'S ONE CONSIDERATION FOR
SOME PATIENTS THAT WE RECRUIT TO
OUR STUDIES AND WILL I KNOW HOW
TO DO THIS AND CAN I BE
COMPLIANT FOR THE DATA WE NEED
AND SOMETIMES THEY'RE NOT AND
THEY'RE NOT ABLE TO.
THAT THE ONE CRITICAL PIECE OF
IT.
THE OTHER PART YOU'VE ASKED
ABOUT WAS MOTIVATION TO
PARTICIPATE IN RESEARCH AND I
AGREE ALTRUISM IS A FACTOR AND
MANY ARE ALREADY UNDERGOING
THERAPY AND WANT TO HELP THE
BROADER COMMUNITY OF PATIENTS
FACING THE CHALLENGES WE ARE
FACING AND THEY DON'T HAVE TO
UNDER GO THE THERAPY -- THEY
DON'T NEED TO PARTICIPATE IN
RESEARCH IN ORDER TO GET THE
THERAPY.
IT'S LIKE ADDING IT ON AS PART
OF THEIR EXPERIENCE.
AND I THINK SOME PATIENTS ARE
PROUD OF THAT.
I THINK ANOTHER POTENTIAL
MOTIVATING FACTOR IS FINDING
WAYS TO ENGAGE THE PATIENT BASED
ON CHALLENGES AND SPECIFIC
NEEDS.
SOME ARE FACING PSYCHIATRIC
SYMPTOMS AND DEPRESSION AND
OUG
AUTONOMIC ISSUE AND THAT WHAT
NEEDS TO BE EXPLORED MORE WITH
DBS.
>> THANK YOU.
>> WE HAVE A 10-MINUTE WARNING.
WHEN IS THIS THE SESSION OVER?
>> QUARTER PAST.
>> I WANT TO GET BACK TO THE
LIST OF THINGS.
IF WE'RE TRYING TO SHARE DATA
PART OF THE REASON IS GIVE
INCENTIVE AND SOMETHING YOU
SAID, SAMEER THE COST TO GET
STARTED IS HARD.
WHEN YOU HAVE TEAMS THAT ARE
DEEP AND KNOW HOW TO BE IN AN
O.R. AND GET FROM THE LAB TO THE
HOME TO HAVE MULTI-MODAL THINGS
THAT MANY TEAMS HAVE BEEN BUILT
DEEP AND INTEGRATIVE AND
OPERATIONS.
THAT PROVIDES A FOUNDATION TO
ADD AN EXPERIMENT ON FROM
SOMEWHERE ELSE.
WE'VE DONE THIS EFFECTIVELY BY
HAVING PEOPLE DO A TASK IN THE
O.R.
THAT'S SHORT AND ALREADY ON TOP
OF SOMETHING GOING ON AND WITHIN
AN INSTITUTION PEOPLE ARE
SHARING THE OPPORTUNITY AND
PATIENTS CAN PARTICIPATE AND ADD
THINGS THAT ADD TO WHAT WE KNOW
ABOUT THAT PATIENT.
I THINK CORY'S VERY PRAGMATIC
SUGGESTION IS EVERYBODY WANTS TO
KNOW WHAT DBS IS AND ARE YOU IN
THE RIGHT PLACE?
I CAN MAKE THE ARGUMENT TRACT OG
GRAPHY AND IMAGING IS ONE WAY
BUT MAYBE YOU WANT TO VERIFY.
ELECTROPHYSIOLOGY COULD BE THE
WAY TO VERIFY.
YOU MAY BE ABLE TO DO A
NON-INVASIVE PROBE OR THE
BAYLO
BAYLOR-UCS TEAM DOES IT IN WOMAN
LOTS OF ELECTRODES AND KEEP THEM
IN THE HOSPITAL BUT SHOULD BE
ABLE TO SCALE IT TO WHAT
EVERYBODY ELSE CAN DO LIKE HIGH
DENSITY EEG OR WITH TMS AND EEG
AND HAVE A CROSS-METHODS AND
EXPERTS AND CORY IS AN EXPERT
BUT TO TAKE AN IDEA AND SAY IF I
CAN DO THAT AT THE INVASIVE
LEVEL, WHERE'S THE TEAM I COULD
DO THAT?
YOU SHARE THE RESOURCES.
IF WE HAD A BUNCH OF INVASIVE
TEAMS DOING THE SAME EXPERIMENT,
EPILEPSY PEOPLE DO THIS ALL THE
TIME.
THERE WAS A WHOLE NETWORK SET UP
IN THE EPILEPSY COMMUNITY TO DO
TASKS ACROSS DIFFERENT PATIENTS
BECAUSE NO ONE TEAM HAD ENOUGH
PATIENTS.
SO THERE'S SO MANY EXAMPLES I
THINK CORY'S SUGGESTION OF
INCENTIVIZING WHETHER IT'S A
SUPPLEMENT, YOU GET TO USE THE
INFRASTRUCTURE OF A TEAM THAT
EXISTS, THAT'S ADDED VALUE TO
THAT TEAM.
THEY LEARN ABOUT A NEW IDEA,
IT'S A METHOD THAT MIGHT BE DONE
THAT CAN SCALE IN AND OUT SIDE
OF AN O.R. AND THIS HAND OFF
LIKE THE REPLAY RACE OF VERY
INVASIVE TO LESS INVASIVE AND
NOT NECESSARILY THE SAME TASK
BUT PEOPLE SOPHISTICATED ABOUT A
QUESTION THAT CAN MOVE ACROSS
SCALE AND ACROSS TIME SO YOU GET
THE DYNAMIC TIME SCALE OVER TIME
AND PEOPLE CAN DO THE
EXPERIMENTS THEY CARE ABOUT AT
EVERY LEVEL OF RESOLUTION.
I THINK IT HITS THAT POINT AND
THEN YOU CAN SHARE ALL THAT DATA
AND PEOPLE WOULD BE VERY
INCENTIVIZED TO BE ABLE TO USE
AND LOOK AT THEIR APPROACH DOWN
SAMPLING OR UP SAMPLING.
>> THANKS, HELEN.
I THINK IT'S A NEXT GENERATION
COLLABORATION THAT WE REALLY
NEED TO INCORPORATE TO MOVE THIS
FORWARD.
I SHITA.
IF WE WANT TO EXPAND THE
NETWORK WHERE WE DO THIS KIND OF
DATA COLLECTION IT'S NOT JUST
PATIENT EDUCATION BUT NOT EVERY
CENTER HAS CLINICIANS INVESTED
IN THE RESEARCH.
AND CONSENTING WOULD BE USEFUL
FOR CENTERS THAT MAY NOT BE
ENGAGED IN RESEARCH IN THAT
EXTEND TO HAVE LIKE INCORPORATE
CENTERS FOR RESEARCH.
I THINK I WANTED TO BRING UP
THAT POINT.
IT HAS BEEN A LEARNING CURVE FOR
ME AND I TOOK FOR GRANTED EVERY
CLINICIAN KNEW HOW TO TALK TO
PATIENTS AND I HAVE HAD PATIENTS
WHO HAVE BEEN DENIED TO DO A
STUDY BECAUSE WE DIDN'T EXPLAIN
IT WELL.
I THINK EDUCATION ON THAT PART
IS ALSO IMPORTANT.
THAT'S IMPORTANT FOR ENGAGING
PATIENTS.
>> ONE INTERESTING POINT IS 90%
OF WHAT WE TALKED ABOUT IS NOT
SPECIFIC TO INTRACRANIAL AND I
THINK THAT'S FINE.
IN FACT I THINK THIS WAS BE
PLANNED AND THERE'S DISCUSSION
WHETHER TO SEPARATE THEM OR NOT.
AS THE NIH ORGANIZATIONERS ARE
TO BE CROSSED OVER BETWEEN
INVASIVE AND NON-INVASIVE
OPPORTUNITIES.
>> ONE QUICK THING THAT'S A HUGE
DIFFERENCE AND RELATES TO WHERE
WE'VE BEEN THE PAST FIVE OR 10
MINUTES, YOU CAN DO NON-INVASIVE
RECORDING AND BRAIN STIMULATION
FOR PEOPLE WITH NO DISEASE AND
AS OF NOW NOBODY HAS VENTURED
INTO LETS TAKE IT INTO A HEALTHY
PERSON TO
[AUDIO DIGITIZING]
AND LET'S JUST THROW SOMEONE IN
FOR 30 DAYS WHO IS OSTENSIBLY A
HEALTHY CONTROL.
THAT WOULD BE A FASCINATING
EXPERIMENT AND WOULD NEED A
NEURAL CONFERENCE TO GET THERE
BUT THAT'S A HUGE DIFFERENCE.
EVERYTHING WE HAVE DONE SO FAR
HAS TO BE ONE STEP OVER FROM THE
BENEFITS AND GETTING TO ALLEN'S
POINT OF TAKING WHAT WE'RE DOING
AND MAKE IT EPSILON BETTER
VERSUS HOW DOES THE BRAIN WORK
CURIOSITY DRIVEN.
MAYBE BOB HAS A FURTHER COMMENT.
>> MY VIDEO'S BLOCKED.
A COUPLE POINTS TO WHAT HELEN
SAID AND WE'VE HAD A CONSORTIUM
OF THREE TO FIVE MED CENTERS AND
THAT YOU LO -- THAT ALLOWS TO
DO TESTS TO ACCUMULATE DATA
BETTER AND A MIKE -- MICROLEVEL
AND I'VE BEEN POSTING ON JOURNAL
WEBSITES FOREVER AND NOBODY
SEEMS TO PAY ATTENTION TO THEM.
WHETHER THAT WOULD BE A VALUABLE
OR NOT I ACTUALLY DON'T KNOW BUT
HAVING COLLABORATIONS ACROSS
THREE OR FOUR DBS SITES WHERE
YOU DO DIFFERENT TASKS AND DOING
A DIFFERENT PERSON TASKS YOU'LL
GET A LOT OF DATA QUICKER.
I THINK THAT'S A GOOD WAY TO GO
AND YOU'RE COMMUNICATING THE
OTHER THING ABOUT THE ETHICS
PART AND WHAT WORKS BASED ON
INPUT FROM WINSTON CHUNG I DON'T
KNOW IF YOU DISCUSSED IT A
MISSED A SESSION YESTERDAY,
TEACH TO LEARN.
AND IF THEY KNOW WHAT THEY'RE
TALKING ABOUT THEY'RE DONE AND
TWO THINGS THEY DON'T GET RIGHT
YOU GO BACK AND GO OVER THAT ON
THE CONSENT JUST TO REALLY MAKE
SURE THEY KNOW EXACTLY WHAT
YOU'RE DOING.
SO I THINK WE'LL BE STARTING
THAT IN THE NEXT SERIES OF
PATIENTS.
>> I THINK WE'RE AT TIME.
THANKS FOR THE RICH DISCUSSION.
I THINK WE'VE GOT A LOT OF THE
JUICE SQUEEZED OUT.
BACK TO ANDREW.
>> I THANK ALL THE PANELISTS FOR
THE RICH DISCUSSION I THINK
COULD HAVE GONE ON LONGER FOR
THE INTERESTING AND COMPLEXITIES
TOE CONSIDER.
AND WE HAVE THE NEXT SESSION AND
IT'S MY PLEASURE TO HAND IT OVER
FOR THE NEXT SESSION.
>> WELCOME TO THE FINAL SESSION.
I THINK A LOT OF THE CONTENT
WOULD BE CONGRUOUS WITH THE LAST
SESSION AND WOULD LIKE TO GET
INTO NON-INVASIVE SPECIFIC
TOPICS AND USE OUR PRESENCE TO
CONSIDER THE NON-INVASIVE
STIMULATION PARTICULARLY TO THE
GENERAL QUESTIONS AND BIG
PICTURE IDEA FOR DATA
HARMONIZATION AND EFFORTS AND
THE NITTY-GRITTY.
THIS IS BY SOMETHING WISE THAT
MIKE FOX BROUGHT UP IN THE LAST
SESSION WAS THAT I THINK YOU
SAID THERE'S AN INFINITE NUMBER
OF COOL THINGS WE COULD DO AND
HOW DO WE CONSTRAIN WHAT WE'RE
DOING BASED ON WHAT WE CAN DO
AND WHAT OUR GOALS ARE?
I'D LIKE TO HAVE A BIT OF A
CONVERSATION TO NARROW DOWN THAT
SPACE A LITTLE BIT.
AND CONSIDERATIONS WITHIN THE
VERY BROAD NON-INVASIVE
STIMULATION ECO SYSTEM MOST
USEFUL FOR ADDRESSING THE
CONCEPTUAL GOALS THAT WERE
RAISED DURING DAY ONE AND IN THE
MODELLING SESSION.
>> THANK YOU, ALEC FOR SETTING
ME UP.
WE'VE BEEN TALKING ABOUT
INVASIVE STIMULATION AND
RECORDING METHODS FOR THE LAST
COUPLE DAYS AND SO I WANT TO
GIVE A BRIEF OVERVIEW OF SOME OF
THE PROS AND CONS AND LOOK AT
DISORDERED AND HEALTHY BRAINS.
THIS ALLOWS TO TEST QUESTIONS
AND FACILITATE INFERENCES ABOUT
TYPICAL BRAIN FUNCTION.
IN PARTICULAR REGIONS AND NOT
LIMITED TO EPILEPSY NETWORKS OR
OTHER AFFECTED LOCATIONS.
YOU ONLY HAVE SO MUCH TIME WITH
A PATIENT IN THE O.R. SO MUCH
TIME THEY'RE ABLE TO PAY
ATTENTION IN THE EPILEPSY
MONITORING UNITS AND CAN PEOPLE
IN FOR MULTIPLE SESSIONS THAT
CAN LAST FOR HOURS AND RUN
THROUGH STIMULATION PARAMETER
SPACES WHEN YOU'RE TRYING TO
TEST THINGS OUT AND MEANS IT'S
NOT TOO DIFFICULT TO INTEGRATE
WITH BEHAVIORAL MEASURES OF ANY
NECESSARY COMPLEXITY YOU WANT TO
TRY TO STUDY OR INCORPORATE.
THE SPECIFICITY IS HORE THAN
EVASIVE SIMULATION.
THE EXPERIMENTAL DESIGNS MUST
ACCOUNT FOR SALIENT SIDE EFFECTS
AND FEELINGS YOU HAVE WHEN
YOU'RE STIMULATED AND PAINFUL
AND DISTRACTFUL AND POTENTIAL
OFF TARGET ON THE PERIPHERAL
NERVOUS SYSTEM AND CRANIAL
NERVES.
AND NON-IAN VASIVE METHODS
UNLIKE INVASIVE STIMULATION
WHERE YOU CAN RECORD AND RO USE
THE ELECTRODES FOR DELIVERING
AND NON-INVASIVE STIMULATION
DOESN'T PLAY WELL WITH THE
METHODS AND THE IMMEDIATE IMPACT
ON NEURAL ACTIVITY.
YOU INJECT FAIRLY LARGE
AMPLITUDES OF ELECTRICITY OR
MAGNETIC FIELDS ON THE OUTSIDE
THEIR HEAD DISRUPTS NEURAL
RECORDING METHODS ELECTRICAL OR
fMRI BASED.
I'D LIKE TO HIGHLIGHT RELEVANT
THEMES FROM DAY ONE I HOPE TO
ADDRESS AS A PANEL AND LET'S
TAKE A BREAK AND INTRODUCE
EVERYBODY ON THE PANEL FIRST.
I THOUGHT IT WOULD BE GREAT IF
EVERYBODY CAN SAY HELLO AND AN A
WORD OR TWO ABOUT YOUR
CONNECTION TO INVASIVE OR
NON-INVASIVE BRAIN STIMULATION
APPROACH.
I'M JOEL WITH THE UNIVERSITY OF
CHICAGO AND WORK IN NON-INVASIVE
AND STUDIES IN EPISODIC MEMORY.
THE NEXT PERSON IS BRUCE LUBER.
>> I'M IN THE INTERIM PROGRAM AT
THE NIMHD.
I'VE SPENT THE LAST 25 YEARS
DOING TMS RESEARCH TRYING TO
FIND WAYS TO ENHANCE PERFORMANCE
IN EXECUTIVE PROCESS.
>> NEXT IS ELISA.
>> I'M AN ASSISTANT PROFESSOR AT
THE NEW JERSEY INSTITUTE OF
TECHNOLOGY.
I DO COMBINED TMS WITH NEURAL
PHYSIOLOGICAL AND TMS EMG AND
STUDY HEALTHY INDIVIDUALS AND
PATIENTS.
>> EARL MILLER.
>> I'M AT M.I.T. AND STUDY
NON-HUMAN PRIMATES AND INVASIVE
AND NON-INVASIVE AND THE GOAL IS
TO DEVELOP NON-INVASIVE TO BE
USED EVENTUALLY IN HUMANS.
>> I'M ALEX OPI TZ IN MINNESOTA
AND I'M A BASIC PHYSICS AND
TECHNOLOGY DEVELOPER.
>> AND DAMIEN FAIR.
>> I'M ALSO FROM THE UNIVERSITY
OF MINNESOTA AND CO-DIRECTOR OF
THE INSTITUTE FOR THE DEVELOPING
BRAIN AND DO IMAGING WITH
FUNCTI
FUNCTIONAL MRI AND HIGH
RESOLUTION INDIVIDUALS AND
GETTING PULLED IN THE HUMAN
INVASIVE AND NON-INVASIVE
MODULATION REALM LEVERAGING THE
TOOLS.
>> COREY KELLER.
>> I USE MODALITIES IN HUMANS TO
UNDERSTAND HOW REPETITIVE
PATTERNS OF INDUCED PLASTICITY
ELEVATE SYMPTOMS OF MENTAL
HEALTH DISORDERS.
>> AND GABRIEL LAZARO MUNOZ.
>> AT HARVARD MEDICAL SCHOOL AND
PSYCHIATRY AND I FOCUS ON
ETHICAL, LEGAL AND IMPLICATIONS
OF TECHNOLOGIES.
>> I'M AT THE LAUREATE INSTITUTE
OF BRAIN RESEARCH.
I'M THE DIRECTOR OF BIO
STATISTICS FOR THE ATLAS BRAIN
DEVELOPMENT STUDY AND HCD STUDY.
I'M CURIOUS IF WE COULD COMMENT
OR DISCUSS HOW OBSERVATIONAL
STUDIES CAN INFORM STUDY AND
HOPEFULLY WE CAN GET TO THAT IN
THE CONVERSATION.
>> AND FINALLY THE CO-CHAIR.
>> I'M A PROGRAM DIRECTOR IN THE
BASIC AND MECHANISTIC BRANCH AT
THE NATIONAL CENTER FOR
COMPLEMENTARY AND INTEGRATIVE
HEALTH AND WE FOCUSSED ON THE
DEVELOPMENT OF NEW NON-INVASIVE
IMAGING TOOLS AND TECHNOLOGIES.
I'M LOOKING FORWARD TO THE
WONDERFUL DISCUSSION ALL OF YOU
WILL LEAD.
THANK YOU SO MUCH.
>> I'D LIKE TO DO EYE HIGHLIGHT
OF RELEVANT THEMES FROM DAY ONE
THAT ARE IMPORTANT TO KEEP IN
MIND TO MOTIVATE OUR DISCUSSION
AND SOME THEMES TO SUMMARIZE
THAT IT'S BENEFICIAL TO MEASURE
THE IMPACT OF STIMULATION ON
BRAIN ACTIVITY DIRECTLY.
AND EXTRA HELPFUL IF THEY
CAPTURE DYNAMICS WHERE PEOPLE
MEANT HIGH SPATIAL, TEMPORAL
RESOLUTION TO MEASURE
BI-DIRECTION INFLUENCES OF BRAIN
ACTIVITY AND STIMULATION.
PEOPLE WERE SAYING BRAIN
ACTIVITY PROVIDES A CONTEXT THAT
CAN MODIFY THE EFFECT OF
STIMULATION ON THE BRAIN AND
STIMULATION AFFECTS BRAIN
ACTIVITY.
IF YOU WANT TO RESOLVE THAT
COMPLEX INTERPLAY IT WOULD BE
HELPFUL TO HAVE THOSE
MEASUREMENTS AND METHODS THAT
CAN RECORD THOSE AND IT'S
IMPORTANT TO CONSIDER A WIDE
VARIETY OF FORMS FROM BRAIN
STRUCTURE LIKE CONNECTIVITY AND
PHYSIOLOGY AND PATTERNS TO
BEHAVIORS OF PERFORMANCE AND TRY
TO ACCOUNT FOR THOSE WHEN TRYING
TO UNDERSTAND THE EFFECTS OF
STIMULATION AND LOOK AT
SOPHISTICATED BEHAVIORAL
MEASURES WITH A WIDE RANGE OF
WHAT THEY THOUGHT BE FROM
NATURALISTIC TO CONSTRAINED AND
LABORATORY BASED.
AND UNDERSTANDING IN ORDER TO
USE STIMULATION AS A TOOL TO
UNDERSTAND HOW BRAIN SUPPORTS
COGNITION.
UNDERSTAND THE LOCAL EFFECTS OF
STIMULATION AND THE DISTRIBUTED
EFFECTS OF STIMULATION
THROUGHOUT THE NETWORK.
AND THAT IT'S IMPORTANT TO
UNDERSTAND THESE ARE TERMS AND
UNDERSTAND BOTH DISRUPTION AND
PERTURBATION IN MANIPULATIONS
AND ENHANCEMENT LIKE EFFECTS
WHAT PEOPLE WERE CALLING
STIMULATION.
AND THAT THE EFFECTS OF
STIMULATION AND ESPECIALLY FOR
THE ENHANCEMENT EFFECTS MAY
DEPEND ON SOME WAY OF MATCHING
STIMULATION TO BRAIN STATE.
IT'S A TOPIC THAT CAME UP
CONSISTENTLY OPPOSED TO USING
HIGH-FREQUENCY STIMULATION TO
MEASURE THE BRAIN STATE AND
MEASURE SOME PATTERN STIMULATION
TO MIMIC WHAT THE BRAIN IS DOING
TO IMPROVE ITS FUNCTION.
AND THE FINAL THEME WAS THAT IT
WILL BE IMPORTANT TO USE METHODS
THAT CAN BE INCORPORATED TO
RELEVANT NON-HUMAN ANIMAL MODELS
TO GO BEYOND IN TERM OF
MECHANISTIC DETAILS WHAT IS
POSSIBLE TO ACCOMPLISH IN HUMANS
AND FOCUSSING ON THE AREAS WHERE
YOU CAN MAKE THOSE CONNECTIONS.
MOTIVATED BY THE THEMES TRYING
TO COME UP WITH QUESTIONS TO
KICK OFF OUR CONVERSATIONS.
LOOKING AT NON-INVASIVE
SIMULATION STUDIES WHAT ARE THE
CHALLENGES AND CONSTRAINTS IN
USING SIMULATION TO ADDRESS THE
CONCEPTUAL IMPORTANCE OF THOSE
WHO HAVE SPOKEN TO THE FIELD.
ONE MORE POINT IS THE DATA
NEEDED TO BE AMENABLE TO
MODELLING THE EFFECTS OF
STIMULATION ON BRAIN BEHAVIOR
RELATIONSHIPS.
SO HERE ARE THE FIVE DISCUSSION
QUESTIONS I THOUGHT WE COULD
START OFF WITH.
SO THE FIRST ONE IS ON THIS
THEME OF PAIRING NON-INVASIVE
STIMULATION METHODS AND NEURAL
RECORDING METHODS.
SO WHAT ARE THE POSSIBILITIES IN
TERMS OF BEING ABLE TO STIMULATE
AND RECORD TO MEASURE LOCAL AND
NETWORK LEVEL EFFECTS OF
STIMULATION.
AND SATISFY THE NEED OF
ANATOMICAL AND SPECIFICITY TO
ADDRESS DYNAMICS.
WHAT LEVELS OF THESE
STIMULATIONS AND RECORDINGS AND
HOPEFULLY THAT'S A GOOD KICKOFF
QUESTION.
WOULD ANYONE LIKE TO JUMP IN?
>> TALKING ABOUT MODULATED
STIMULATION CONNECTED TO A
NON-INVASIVE RECORDING IN HUMANS
AND HELPING PARTICIPANTS OR
MEASURES LIKE EEG, fMRI, THIS IS
AT THE RECORDING LEVEL IS
LIMITED.
AND HAVE INNOVATIVE RECORDING
AND WANTED TO MAKE A BRIDGE TO
THE EARLIER SESSION HIGHLIGHTING
INVASIVE MEASUREMENTS IN
OCCUPATIONS OR IN NON-HUMAN
PRIMATES FOR EXAMPLE STUDY THE
MECHANISM OF NON-INVASIVE
STIMULATION AND SIGNALS THAT ARE
SOMEWHAT TRANSLATIONAL TO
NON-INVASIVE RECORDING AND
THERE'S BEEN A GREAT OPPORTUNITY
TO STUDY THAT
>> WHEN WE TALK ABOUT
SPECIFICITY THERE'S SPATIAL
SPECIFICITY AND FOR THE
INFLUENCES OF THESE ONGOING
DYNAMICS AND OSCILLATIONS, THEY
ACTUALLY PRODUCE NETWORK EFFECTS
AND SPATIAL SPECIFICITY IS THERE
AND MAYBE BE LESS IN TERMS OF
INFLUENCE BUT IN TERMS OF THE
AFFECTS YOU WANT SOME
SPECIFICITY IN THE ACTION.
I WANT TO MAKE A POINT THAT I
THINK PEOPLE WILL ASSUME THERE'S
A RELATIVELY STRAIGHT
CORRESPONDENCE WITH THE ACTIVITY
INSIDE THE BRAIN AND SKULL.
IT'S A FILTERING PROBLEM THE
SKULL AND MUSCLES GET RID OF THE
FREQUENCIES BUT IT'S NOT
NECESSARILY THE CASE.
MARCUS SIEGEL DID A STUDY
SHOWING THE CORRESPONDENCE FROM
EEG INSIDE THE SKULL AND OUTSIDE
THE SKULL OF THE MONKEYS YOU GET
MORE DEEP LAYER ACTIVITY FROM
EEG IN THE VISUAL CORTEX.
THE CROSS-SPECIES CONNECTIONS
ARE VERY IMPORTANT.
WE'RE DOING WORK WHERE WE'RE
DOING RECORDING AND STIMULATION
INSIDE THE SKULL AND RECORDING
THE EEG OUTSIDE OF THE SKULL TO
FIGURE OUT WHAT THE RULES ARE.
AND MAYBE THE RULES ARE
RELATIVELY STRAIGHTFORWARD AND
THEN WE CAN UNDERSTAND WHAT'S
GOING ON OUTSIDE THE SKULL
BETTER.
>> AND MY LAB USE TMS fMRI AND
THERE'S INTRACRANIAL EEG FOR
TEMPORAL SPECIFICITY.
WHAT COULD BE USED AT SCALE AND
WHAT ARE PRACTICAL CHALLENGES TO
USING THEM AT SCALE?
AND SIMULTANEOUS THE STUDY AND
MY MIND IS EXPLODING AT THE
METHODS AND WOULD BE GREAT WHICH
METHODS YOU USE AND HOW SPECIFIC
THEY ARE THAT IN TERMS OF THE
SPATIAL AND TEMPORAL EFFECTS YOU
CAN MEASURE ON THE BRAIN.
HOW SPECIFIC CAN YOU BE AND HOW
PRACTICAL IS IT TO SCALE THOSE
THINGS UP.
>> YOU TALKED ABOUT TEMPORAL AND
SPATIAL RESOLUTIONS.
SO ALSO WITH COMBINING WITH EMD
WE CAN ALSO GO INTO SYSTEMS
SPECIFIC THINGS.
TMS ACTIVATES DIFFERENT NEU
NEUROTRANSMITTER AND THE
EXCITATORY SYSTEMS AND COMBINING
TMS WITH EEG WE CAN
DIFFERENTIATE THOSE SYSTEMS.
WE CAN DO SOME SYSTEMS SPECIFIC
THINGS WHEN WE COMBINE WITH THE
METHODS.
>> WHAT IS THE METHOD LEVEL
SPECIFICITY?
A THEME THAT CAME UP IS DTI
CONNECTIVITY PREDICT THE
SIMULATION.
CAN YOU GET AT THAT IN TERMS OF
THE CHALLENGES WITH USING EEG OR
OTHER METHODS TO GET AT THAT?
>> THERE ARE SOME KNOWLEDGE OF
PREVIOUS STUDIES HAVE SHOWN LIKE
THE EARLY RESPONSES WOULD BE
MORE LOCAL AND THE LATER
RESPONSES IS MORE GLOBAL.
THAT'S SOMETHING WE DON'T FULLY
UNDERSTAND.
DAMIEN?
>> I'M BIASSED ON THIS
PARTICULAR QUESTION OBVIOUSLY
BUT AND THEY'RE NOT ALLOWED TO
DO ANY NEURAL MODULATION STUDY
UNLESS YOU GET PRECISION
FUNCTION AND WE'RE SEEING AND
THERE'S SPATIAL FESTIVITY FOR
THE TARGETS AND APPLICATION AND
INFORMED BY PRECISION DATA
METHOD.
IT DEPENDS ON THE SPECIFICS THE
QUESTION.
NON-INVASIVE STIMULATION COMES
IN SEVERAL FORMS.
THERE'S OTHER ADVANCED IMAGING
TECHNIQUE AND IMAGING AND OTHERS
ARE IMPORTANT BUT THAT'S THE
SPATIAL PART THAT'S IMPORTANT
AND COMBINING THAT WITH THE
TEMPORAL INFORMATION WHERE YOU
CAN ESSENTIALLY TIME THE
STIMULATION TO SPECIFIC POINTS
AND LAYERS OF ACTIVITY I THINK
IS COMBINED HAS A HIGH POTENTIAL
TO REALLY ADVANCE AT THE
TREATMENT LEVEL AMONGST OTHER
THINGS.
AND I'LL LEAVE IT TO MY EXPERT
FRIENDS TO EXPLAIN THE TEMPORAL
PIECE.
>> COREY, YOU'VE HAD YOUR HAND
UP.
>> GREAT QUESTION.
I THINK IT'S WORTH NOTING THAT
THOSE TOOLS THAT SCALE ARE
MECHANISTICALLY MORE AMBIGUOUS
THAN THOSE THAT DON'T AND YOU
USUALLY HAVE POORER SPATIAL OR
TEMPORAL RESOLUTION.
WE HAVE INVASIVE RECORD WITH
NICE SPATIAL AND TEMPORAL
RECORDING BUT DON'T SCALE TO
MANY POPULATIONS OR TO MANY
PEOPLE.
I THINK THAT'S WHY WE NEED TO
USE INVASIVE RECORDINGS LIKE TMS
EEG AND fMRI TO BETTER
UNDERSTAND THE TOOLS THAT SCALE
BETTER.
IN DOING SO WE CAN THEN MOVE TO
THAT LEVEL.
BEFORE THAT WE NEED TO LEARN A
LOT AND THE QUESTION OF fMRI
VERSUS EEG, I'M BIASSED.
I THINK THE TEMPORAL RESOLUTION
IS CRITICAL BUT OF COURSE THE
SPATIAL RESOLUTION IS AS WELL.
PAIRING THE NON-INVASIVE TOOLS
WE HAVE TOGETHER IS ABSOLUTELY
CRITICAL.
>> I THINK THIS IS SOMETHING
THAT MIGHT COME UP LATER ON BUT
THAT SEEMS LIKE IT MIGHT PRESENT
ITSELF AS AN OPPORTUNITY FOR
COORDINATED EFFORTS IN TERM OF
DIFFERENT LABS THAT FOCUS ON
DIFFERENT PIECES OF THAT PUZZLE
USING DIFFERENT METHODS.
>> TO DO THESE TECHNICAL
MODALITIES WELL WHETHER IT'S
TMS, EEG OR fMRI, IT TAKES A LOT
OF TIME AND EFFORT AND IS HARD
TO SCALE EVEN ACROSS LABS THAT
DO IT WELL.
SO THESE COORDINATED EFFORTS
COLLABORATIONS ACROSS LABS WHO
HAVE THESE EXPERTISE IS
DEFINITELY CRITICAL.
>> ASK I THINK DAMIEN JUST SAID
SOMETHING WE ALWAYS DO WHICH IS
YOU HAVE TO HAVE TOTAL CONTROL
OVER YOUR PSYCHOLOGICAL TASK.
YOU HAVE TO KNOW ALL ABOUT IT
BEFORE YOU EVER BRING ANYBODY
INTO A SCANNER OR GIVE THEM TMS.
THAT'S JUST SOMETHING I DON'T
THINK IS DONE WELL ENOUGH AND
I'M AN EXPERIMENTAL PSYCHOLOGIST
AND MAY BE BIASSED BUT IT'S NOT
DONE WELL ENOUGH THAT YOU HAVE
TO HAVE CONTROL OVER YOUR TASK
AND BEHAVIOR BEFORE YOU EVER DO
ANYTHING ELSE.
BUT I ALSO WANTED TO AGREE WITH
JOEL ABOUT I WOULD LOVE SCALING
UP TMS fMRI.
BUT WE'RE JUST STARTING A
REAL-TIME NEURAL FEEDBACK TMS
EXPERIMENT AND TAKING US A YEAR
AND A HALF TO GET IT ALL SET UP.
AND THERE'S A LOT OF MOVING
PARTS.
WE'RE ALSO USING ARE HIGHER
NUMBER OF CHANNELS FROM THE
GROUP THAT MAY MAKE IT MORE
DIFFICULT.
THAT'S WHAT COULD BE SCALED UP
AND ONE LAST THING WHICH IS
USING THIS WITH fMRI
CONCURRENTLY AND EEG ARE MY
DREAM.
I WORKED WITH PAUL SHIDA AT
COLUMBIA JUST DOING OBJECT
DISCRIMINATION WITH NOISE ADDED
AND THERE'S GREAT PSYCHO
PHYSIOLOGY AND DID EEG AND FOUND
COMPONENTS AND THE RIGHT TIMING
TO DO WITH EEG COMPARED TO THE
COMPONENTS AND WHAT THE
COMPONENTS WERE DOING AND FOUND
THREE NETWORKS ASSOCIATED WITH
THE ABJECT DECISION PROCESS
FOCUSSED ON THE LATERAL COMPLEX
AND GAVE ENOUGH INFORMATION WE
KNEW TO STIMULATE AT A CERTAIN
TIME AND STIMULATED DIFFERENT
TIMES AND WHEN WE STIMULATED
AROUND 200 MIL SECONDS WE WERE
ABLE TO DISRUPT THAT DECISION
PROCESS.
AND USING THE EEG TOGETHER WITH
THE MRI ALLOWED US TO FOCUS WHAT
TO DO.
>> I HOPE WE GENERATE A LAUNDRY
LIST OF IDEAS WHAT PEOPLE
PRIORITIZE IN TERMS OF THE
METHODS LATER ON WE CAN TALK
ABOUT THE CHALLENGES TO SCALE
THEM UP AND DOING THEM ACROSS
SITES OR IN A LARGER WAY.
ALEX.
>> I THINK I WANT TO RESPOND AT
THE INTERSECTION OF DAMIEN AND
EARL BECAUSE WE POINTED OUT ALL
LEVELS OF SPECIFICITY NEED TO BE
MAPPED.
AT THE SAME TIME, DAMIEN IS
RIGHT THAT IF YOU DON'T IMAGE
EVERYBODY WITH THE SAME PROTOCOL
YOU'RE DROPPING DATA ON THE
FLOOR.
I WANTED TO KEEP COMING BACK TO
THE OVERLAP OF LEVELS OF
ANALYSIS AND YOU MAP THE
FUNCTIONAL NETWORK AND YOU COULD
MAP THE WEAR BY PRECISION
MAPPING AND THE OSCILLATION EARL
WAS TALKING ABOUT AND THOSE
TECHNIQUES CAN BE COMBINED TO
TEACH US MORE THAN ANY
INDIVIDUAL ONE AND THAT'S AGAIN
THE SAME THING IF YOU CAN
PROVIDE INVASIVE AND
NON-INVASIVE TOGETHER YOU'LL
LEARN MORE.
>> YOUR NAME IS TOO MUCH LIKE
ALEX SO I'M GOING TO CALL YOU
WIDGE FROM NOW ON.
>> WE'RE BOTH FROM MINNESOTA.
AND HIGHLIGHTING THE TEMPORAL
ASPECT.
I THINK WE LEARN SO MUCH AND IT
DEPENDS ON THE STATE OF THE
MOTOR CORTEX SO IF YOU ALIGN
STIMULATION AT DIFFERENT PHASES
YOU GET DIFFERENT RESPONSES
SHOWN AT SIMILAR TIMES AND
PEOPLE ARE NOW REALIZING FOR
OTHER BRAIN AREAS THE PREFRONTAL
BETA THERE'S AN OPPORTUNITY TO
DO THOSE REAL TIME STIMULATION
AND TMS EEG.
IT'S A BIG OPPORTUNITY THERE.
>> FOR EVERYONE ON THE CALL I
WANT TO BRING UP SOMETHING IN
THE CHAT AND TO THE POINT ABOUT
SCALABILITY AND MECHANISTIC.
AND A NICE FOLLOW-UP POINT IN
THE CHAT THAT SAYS UNDERSTANDING
ARE TWO DISTINCT AND PARALLEL
APPROACH AND APPROACH MAY BE
SCALED BUT DOESN'T INCLUDE THE
NEAT FOR EARLY STAGE MECHANISTIC
QUESTIONS.
>> THANK YOU.
I ACTUALLY CAN'T SEE THE CHAT.
>> GREAT.
IN THE INTEREST OF TIME LET'S --
OKAY, HERE WE GO.
I ACCIDENTALLY CLICKED THE
ADVANCE BUTTON ANYWAY.
IN TERMS OF NON-INVASIVE
STIMULATION IT WOULD BE GOOD TO
TALK ABOUT THE INDIVIDUAL
DIFFERENCES AND QUESTION AND
STRATEGIES FOR HOW DO YOU ASSESS
INDIVIDUAL DIFFERENCES IN A WAY
THAT I'M COMING FROM THE TMS
PERSPECTIVE WHERE YOU MIGHT WANT
TO MEASURE EACH PERSON'S MVP TO
MAKE SURE YOU'RE CALIBRATING
YOUR SYSTEM SIMILARLIY AND TAKE
THAT MEASURE TO ACCOUNT IN YOUR
STUDY AND MAY BE THING FOR TRANS
ELECTRICAL STIMULATION AND WAYS
TO LOOK AT DIFFERENCES AND HOW
EACH PERSON RESPONDS TO
STIMULATION AND HOW DO YOU
ACCOUNT FOR EACH PERSON'S STATE
AND, YEAH.
I THINK COREY, YOU HAD YOUR HAND
UP ALREADY.
>> I'M REFRAME IT.
I THINK ONE QUESTION IS HOW DO
WE DETERMINE IF THESE ARE ACTUAL
INDIVIDUAL DIFFERENCES?
WE ENSURE OUR DATA QUALITY IS
SUCH THAT WE CAN ANSWER THAT
QUESTION.
SO WES HAD A GREAT COMMENT
ASSESSING PARTICIPANTS WOULD BE
GOOD FOR SOURCING
DIFFERENTIATING VARIATION AND
THE STATE IS CRITICAL LIKE ALEX
MENTIONED AND GETTING AN MEP
FROM FIVE MINUTES TO THE NEXT
DEPENDING ON ALERTNESS AND A
MILLION OTHER THINGS IN AN
INDIVIDUAL.
AND THE MEASUREMENT TOOL.
WE USE TMS EEG AND THE SIGNAL TO
NOISE IS PRETTY LOW.
HOW DO WE BOOST THAT TO GET THE
SAME MEASUREMENT EVERY SINGLE
TIME TO BE ABLE TO ANSWER THE
QUESTIONS?
THERE'S SOURCES OF VARIABILITY
NOT NECESSARILY INDIVIDUAL
VARIABILITY I THINK WE NEED TO
DO BETTER AT ANSWERING THAT
QUESTION.
>> ALEX.
>> THIS GETS TO THE PROBLEM OF
THE CONTROLS AND HOW TO ENSURE
AND FOR TMS WE HAVE THE MEASURE
OF THRESHOLD FROM PROMOTER
CIRCUITS AND YOU CAP USE A
SIMULATION FOR EACH PARTICIPANT
AND CAN DELIVER THOSE AND THEY
VARY A LOT AND THIS IS SOMETHING
THE FIELD HAS NOT REALLY FOUND
GREAT TOOLS TO ACCOUNT FOR THAT
AND SOME VARIABILITY IS ON THE
MODELS OUT ABOUT NOT PERFECT AND
MEASURING MAY BE A WAY TO ENSURE
MORE HARMONIZATION BASED ON JUST
THE DELIVERED DOSE OF BRAIN
SIMULATION.
>> HAVE THERE BASKETBALL KEY
VARIABLES ACROSS SITES TO MAKE
SURE YOU'RE DOING THINGS IN A
STANDARDIZED WAY IN TERMS OF
APPLICATIONS?
AND LOOKING AT INDIVIDUAL
DIFFERENCES AND THE VARIATION
ISN'T JUST DUE TO NOISE.
>> MAYBE HARMONIZE IT SO YOU CAN
HAVE SIMULATION AND MEASURE THAT
AND DO HARMONIZATION BASED ON
THE DELIVERY OF BRAIN STATE.
>> DOSING AND TARGETING HAVE
BEEN WORKED ON AND WE ALWAYS DO
A MOTOR THRESHOLD.
THERE'S ARGUMENTS ABOUT THAT
ONCE YOU LEAVE THE MOTOR CORTEX
AND THERE'S WAYS TO GET THE ACT
DOSE AND USING THE MODELLING AND
A LOT OF WORK IS BEING DONE WITH
THAT AND PROBABLY MORE SHOULD BE
DONE SO WE HAVE SOME
CONCLUSIONS.
AND RELATED TO THAT IS TARGETING
WHERE EVERYBODY OBVIOUSLY VARIES
AND TAR GETTING INDIVIDUALIZED
fMRI AND SO YOU WANT TO FOR
INSTANCE FROM 2009 COMPARE
ACROSS VARIOUS METHODS AND FOUND
THAT TO BE THE BEST AND WE ALL
THOUGHT IT WOULD IN.
THE PLACE BEING STIMULATED IS
DIFFERENT IN PEOPLE AND HOW FAR
AFIELD CAN YOU GO AND HOW BIG DO
I MAKE THE MASK?
WHAT'S THE ACTUAL FUNCTIONAL
AREA INVOLVED.
YOU DON'T WANT TO LEAVE TO BE
ABLE TO STILL STIMULATE THE SAME
NETWORK BUT ACCOUNT FOR
VARIABILITY AND ANATOMY AND WITH
ELECTRICAL STIMULATION I DON'T
KNOW WHAT TO DO BECAUSE YOU
STICK ELECTRODES ON THE HEAD AND
JUST SEE IN DIFFERENT PEOPLE HOW
IT CREATES A DIFFERENT SET OF
CIRCUMSTANCES BASED ON THEIR
ANATOMY IN THEIR BRAIN AND WHERE
THE ELECTRICITY GOES.
THAT HAS TO BE WORKED OUT TOO
FOR ELECTRICAL STIMULATION TO BE
A MATURE SCIENCE.
>> LATER WE CAN TALK WHETHER
THERE ARE AVAILABLE PARAMETERS
AND METHODS FOR EASE OF EASILY
PULLING OUT THE DATA TO
AGGREGATE THAT ACROSS SITES.
>> THINKING ABOUT INDIVIDUAL
DIFFERENCES -- SO IN GENETICS
THERE'S DISCUSSION ABOUT
RETURNING CLINICALLY RELEVANT
RESULTS.
IS THAT SOMETHING THAT IS PART
OF THE NEURO EDTHICS DEBATE IN
THIS SPACE.
I GUESS NOT.
BUT JUST TO BRING THAT UP THAT
HEY, YOU MAY GET TO A POINT
WHERE YOU ARE GENERATING
CLINICALLY RELEVANT INFORMATION
IN THE RESEARCH AND IT'S
IMPORTANT TO CONSIDER WHAT KIND
OF RESPONSIBILITIES WE MAY HAVE
TO RETURN SOME OF THAT
INFORMATION I THINK COULD BE
CLINICALLY USEFUL.
>> IT'S TRUE.
I THINK THE NON-INVASIVE
STIMULA
STIMULATION CAN WORK WITH THE
DISEASE MODELS AND STATES AND
POTENTIAL FOR AGGREGATING DATA
PART OF TMS TREATMENTS FOR
THINGS LIKE DEPRESSION AND LIKE
SOMETHING SHAN TALKED ABOUT
YESTERDAY.
THE QUESTIONS ARE VERY RELEVANT
BUT OUR SILENCE SHOWS OUR
IGNORANCE OF CONSIDERING THEM.
>> I WANT TO HIGHLIGHT THEMES
COMING HERE AS WE HAVE IN THE
LAST PANEL WHERE INVESTMENTS IN
BUILDING BASIC STANDARDS AND
SHARED ACROSS DIFFERENT UNITS.
INVESTMENTS IN TYPES OF WHAT CAN
BE SHARED, EASILY USED BY
MULTIPLE GROUPS TO INTEGRATE
THIS INFORMATION ACROSS METHODS
AND PERSONALIZED METHODS.
YOU CAN SEE MOST THESE
ACTIVITIES WERE PEOPLE RUNNING
THEIR OWN LABORATORIES.
THAT MAKES IT HARD TO REPLICATE
AND THE DIFFICULTIES WE'RE
TALKING ABOUT YOU CAN IMAGINE IF
THERE ARE SOME INVESTMENTS IN
TOOLS TO BUILDING STANDARDS SO
PARAMETERS CAN BE EASILY SHARED
AND INTEGRATED INTO THEIR
SYSTEMS THEN IT WILL MAKE THESE
IDEAS A LOT MORE FLUID.
>> GREAT POINT.
>> THE REASON NOBODY ANSWERED IS
WE HAD TO THINK ABOUT IT BECAUSE
BASICALLY WE'RE NOT GOOD FLUFF
AT -- ENOUGH TO CHANGING THE
BRAIN.
WE HAVE POTENTIAL BUT WE DON'T
DO THAT MUCH DAMAGE OR CREATE SO
MUCH ENHANCEMENT THAT THE
QUESTIONS HAVE BECOME PERTINENT
RIGHT AWAY.
I'M HOPING THEY WILL BE.
>> TO COMMENT QUICKLY, EVEN IN
HEALTHY INDIVIDUALS THAT YOU MAY
BE STUDYING YOU PLAY GET TO A
POINT WHERE YOU START
IDENTIFYING CERTAIN SIGNALS THAT
MAY SUGGEST SOMETHING CLINICALLY
RELEVANT.
SOMETHING TO KEEP IN MIND.
>> ALEX.
>> THERE'S DETE SHARING AND DATA
AGGREGATION BECAUSE OF THE
STANDARDS DEVELOPED AND THEY
DEVELOPED FOR THE BRAIN
STIMULATION FIELD YOU MAKE THE
EFFORTS FOR THE DEVICE AND
PLACEMENT AND MAKE THE LARGER
SCALE EFFORTS MORE FEASIBLE SO
THAT WOULD BE A NEED FOR THOSE
SOFTWARE TOOLS AS DAMIEN
MENTIONED.
>> HOW BIG OF AN ENDEAVOR THAT
WOULD BE, ALEX?
I'M THINKING OF THE VARIATION
AND DO YOU NEED COIL MODELS FOR
EVERY TMS SYSTEM?
THAT'S A GREAT POINT.
THE INFRASTRUCTURE DOES EXIST
AND WILL RECORD THOSE AND HAVE
DIFFERENT COILS TO ESTIMATE THE
DOSE AND IT'S MORE LIKE BRINGING
THE EXISTING PARTS TOGETHER AND
THEN GET BUY IN FROM THE FIELD
AT LARGE AND EVERYONE NEEDS TO
PULL THE DATA IN THE FORM AND
SHARE THAT AND PUSH THAT.
THERE'S SOFTWARE TOOLS AND THAT
LINE.
>> I WANTED TO BRING UP THE
VARIANCE AND WITH TO THE RIGHT
DESIGN IS POSSIBLE FOR
EXPERIMENTAL ERROR AND EXPLAIN
VARIATION AND DUE TO THE STUDY
AND WONDERING IF PERHAPS THIS IS
WHERE A LARGE LONGITUDINAL STUDY
LIKE ABCD COULD BE HELPFUL AND
WONDERING IF YOU CAN WEIGH IN?
>> IT'S ALREADY POSSIBLE AND
BECAUSE OF THE DESIGN AND
SOURCES ARE FOR OTHER
CHARACTERISTICS.
I DON'T KNOW ENOUGH ABOUT THE
WHAT IS HELPFUL TO KNOW ABOUT
INDIVIDUAL VARIATION VERSUS
RANDOM ERRORS AND WONDERING IF
ANYONE CAN COMMENT ON THAT?
>> ONE WAY TO COMMENT ON THAT
FRONT WAS THAT WE'VE BEEN
LEVERAGING THESE STUDIES WITH
REGARD TO NEURAL MODULATION.
IT'S CRITICAL AND THERE WILL BE
SCENARIOS WHERE GETTING THAT
TYPE OF DATA IS JUST NOT
POSSIBLE.
MAYBE THE NEXT BEST THING IS
GENER
GENERATE PROBABILITY AND LEVEL
OFF THE POPULATION STYLE DATA.
WE PUBLISHED A FEW MONTHS AGO A
PAPER IN NATURE AND NEUROSCIENCE
THAT BEGAN TO EXPLORE THE IDEA
OF PROVIDING WHAT DO WE DO WE
DON'T HAVE THE INFORMATION TO DO
THE PERSONALIZED TARGETING.
DO YOU GO BIND OR THE NEXT THING
IS BASED ON POPULATION
STATISTICS?
>> COREY.
>> ONE ON THE DATA SHARING
EFFORTS WOULD BE INTERESTING TO
IMPLEMENT.
WE SHARE EEG fMRI DATA AND
COORDINATES OF OUR STIM HAITIAN
SITE AND THE INTRICACIES OF EACH
PULSE ALONG A THREE-HOUR
STIMULATION RECORDING IN ANGLE,
LOCATION, INTENSITY WOULD LEND
ITSELF TO INTERESTING ANALYSIS.
ON HOW THEY IMPACT THE
STIMULATION AND HOW IT'S
DELIVERED, IT'S A GREAT POINT.
I DON'T THINK WE KNOW THAT MUCH
RIGHT NOW.
I THINK THERE'S GREAT EFFORTS BY
SEAN AND NOLAN AND OTHER PEOPLE
AROUND HOW TO INFLUENCE HOW TMS
IS DELIVER AND WHERE WITHIN THE
PREFRONTAL CORTEX FOR TREATMENT
OF DEPRESSION AND THERE'S BRAIN
STATE AND LEVEL OF ALERTNESS IS
KEY PERCEPTION OF THE TMS PULSES
INFLUENCES THE NEURAL EFFECTS
AND THE UNDERLYING CIRCUITS IS
SOMETHING WE NEED TO BETTER
UNDERSTAND YOU WE DON'T HAVE
GREAT TOOLS TO MEASURE THE
FUNCTIONAL CONNECTIVITY
DIFFERENCES AT BOX AND PERTURB
AND MEASURE THE NEURAL EFFECTS
OF THE CHANGES AT THE CIRCUIT
LEVEL.
SO I THINK HELEN ASKED A GREAT
QUESTION BUT I DON'T KNOW IF WE
HAVE THE TOOLS RIGHT NOW TO
DESIGN THE STUDIES TO ADDRESS
THOSE QUESTIONS.
MAYBE SOMEONE WOULD SAY THAT'S
NOT TRUE.
CERTAINLY FROM A TMS EEG POINT
OF VIEW WE CAN MEASURE THE
CONNECTIVITY WITH fMRI BUT WHEN
WE DO EEG WE DON'T LOOK AT THE
NET ABLE OR ABLE TO LOOK AT IT
THAT MUCH.
WE USUALLY LOOK AT LOCAL
EXCITABILITY AND YOU CAN DO SOME
OF THAT WITH SOURCE IMAGING AND
MAYBE WITH BRUCE'S APPROACH OF
PAIRING EEG AND fMRI WE CAN GET
AT THAT QUESTION BUT IT'S
TRICKY.
>> WHAT ABOUT YOUR WORK WITH
STEREO EMS AND AMENABLE TO
CAPTURING THE STATE AT A
SPECIFIC LOCATION AND MEASURING
HOW THAT IMPACTS THE TMS OR
STIMULATION.
>> THERE'S CAVEATS AND THE
SENSORY EFFECTS OF TMS AND HOW
IT AFFECTS THE NEURAL ACTIVITY
AND CONFOUNDS INTERPRETATION IS
STILL THERE WHEN YOU MEASURE
INSIDE THE BRAIN TOO.
THERE'S STILL LOTS OF ARTIFACTS
FROM TMS THAT SHOW UP INSIDE THE
BRAIN.
SO WHILE IT DOES YIELD HIGH
SPATIAL TEMPORAL RESOLUTION WITH
INTRACRANIAL EEG AND QUAN
ADDRESS SOME COMMENTS HELEN'S
LOOKING AT SPATIAL AND NEURALLY
LOCAL RESPONSES TO TMS IS STILL
IN A VERY UNIQUE POPULATION.
AND DIFFICULT TO OBTAIN IT'S
ALSO DIFFICULT TO STANDARDIZE
THE LOCATION AND INTENSITY AND
THIS IS IN A NEURO SURGICAL
POPULATION AND NOT EASY TO GET
GREAT RECORDINGS EITHER.
>> I KNOW MY VIDEO MAY NOT WORK
BUT I'LL JUST TALK.
I GET WHERE YOU'RE GOING AND WHY
IT DOESN'T SEEM POSSIBLE.
BECAUSE NEURAL NAV PEOPLE AREN'T
GETTING THIS AT BASELINE WHETHER
IT'S TOMOGRAPHY AND BASELINE AND
THE INTEGRITY OF THE WHITE
MATTER WHERE YOU THINK YOU'RE
STIMULATING AND FOR US THE DBS,
YOU KIND OF CAN MODEL THE EXACT
BIG BUNDLES YOU'RE IN.
AS I READ THE TMS LITERATURE AND
THE WORK YOU KIND OF YOU DON'T
HAVE THE PROBLEM BUT ACCURACY
COULD BE MODELLED BY HOW THE
OUTCOME IS AND YOU HAVE PEOPLE
WITH MORE DURABLE OUTCOME, LESS
DURABLE OUTCOME.
WE FOUND THAT THE DAMAGE TO THE
WHITE MATTER EVEN IN PEOPLE WHO
GET BETTER DELAYS HOW LONG IT
TAKES TO GET STABLY WELL AND IF
EXTRAPOLATED YOU COULD START TO
LOOK AT MAPS OF DAMAGE AND STA
ARE THE TO RELATE THESE MACHINE
LEARNING METHODS MAYBE IN A WAY
THAT ISN'T AS GRAN YOU AS NOW
BUT MAY ADD A LAYER OF
EXPLAINABILITY AND MERGE DATA
SETS TO COLLECT DATA THAT COULD
RULE IT IN OR OUT AND I'LL STEP
OUT BUT WANTED TO THROW THAT IN
FOR THE DISCUSSION.
>> DOES ANYONE WANT TO FOLLOW-UP
BEFORE WE CONTINUE?
IN TERMS OF DESIGNING IF WE WANT
TO USE STIMULATION AS A TOOL TO
UNDERSTAND BRAIN BEHAVIOR
RELATIONSHIPS, MECHANISMS OF
COGNITION, IT HAS TO BE DONE IN
THE CONTEXT OF COGNITIVE TASKS.
ARE THERE BEST PRACTICES TO MAKE
SURE YOU CAN INTEGRATE DIFFERENT
FORMS OF BRAIN STIMULATION WITH
THE COGNITIVE TASKS WE MAY BE
INTERESTED IN AND SUBJECTIVE
SIDE EFFECTS OF STIMULATION AND
MAKE SURE THOSE THINGS AREN'T
INFLUENCING TASK PERFORMANCE AND
NON-SPECIFIC WAYS YOU CAN
INTERPRET THE EFFECTS OF
STIMULATION ON BEHAVIOR?
I THOUGHT IT WOULD BE NICE TO
HAVE A CONVERSATION ABOUT THINGS
PEOPLE TYPICALLY DO TO HANDLE
THESE SOURCES OF DISRUPTION IN
TERMS OF YOUR INFERENCES WHEN
YOU PUT BRAIN SIMULATION AND
BEHAVIOR TOGETHER.
>> YOU TRY TO CREATE THE BEST IF
YOU WANT TO DO ONE CONTROL OF
SHAM FOR INSTANCE AND FEELING IN
THE CORTEX THAT CONTRACTS
MUSCLES AND TRY TO USE
ELECTRICAL STIMULATION BUILT
INTO HAD MY SYSTEM.
YOU CAN CREATE THE TMS ON THE
BRAIN AND HOPE YOU CAN SEE A
PERFORMANCE TEST AND WITH
BEHAVIORAL MEASUREMENTS IN TERMS
OF INDIVIDUAL DIFFERENCES AND
STRATEGY AND THINGS LIKE THAT TO
KEEP IN MIND USING A REACTION
TIME AND WE SAW NOTHING AND
USING DRIFT MODELS TO TAKE IN
DISTRIBUTION AND SUBJECTIVE
STRATEGIES WE FOUND A POWERFUL
EFFECT.
USING A GOOD PHYSICAL MODEL IS A
GOOD ASPECT TO THIS AS WELL.
>> I THINK THE SLIDE RAISES THE
QUESTION NICELY.
WE'VE BEEN FOCUSSED ON DATA
COLLECTION INITIATIVES AND
MECHANISTIC STUDIES BUT YOUR
QUESTION HAS UNIQUE CHALLENGES
AND POTENTIALLY UNIQUE VALUE TO
IT.
I WANT TO HIGHLIGHT ONE THING
THE NATURALISTIC TMS WE DO FOR
DEPRESSION WHERE WE ADMINISTER
30 TO 50 SESSIONS ACROSS
MULTIPLE WEEKS OR AND OUTCOMES
TAKE WEEKS OF STIMULATION.
THE DEPRESSION DOESN'T GET
BETTER UNLESS YOU'VE DONE THREE
WEEKS OF DAILY TMS SESSION.
IT'S IMPORTANT TO COMPLIMENT THE
DATA COLLECTION INITIATIVES WITH
A NATURALISTIC DATA COLLECTION
INITIATIVE OF PEOPLE GETTING
CLINICAL TMS BECAUSE YOU'RE
TALKING ABOUT DIFFERENT SESSIONS
AND TIME SCALES AND I THINK
THERE ARE NATURAL EXPERIMENTS
GOING ON OUT THERE THAT CAN BE
SCALABLE AND CAN BE CAPITALIZED
ON TO UNDERSTAND THE STIMULATION
EFFECTS.
>> THERE'S TMS OVER LONG PERIODS
LIKE OVER TWO, THREE HOURS.
MANY LABS HAVE FOUND THEIR OWN
INTERNAL WAYS TO MAKE SURE THE
INDIVIDUAL DOES NOT FALL ASLEEP
OR OF SOMETHING AND SOME PEOPLE
SHOW THEM LIKE A MOVIE OF A
TRAIN OR SOMETHING AND SOME
LOOKED AT PHOTOS WHERE SOME
PEOPLE TALK TO THE PARTICIPANTS
AND LOOK AT THEIR OWN STRATEGIES
AND NOT THAT THE PART OF THIS
KIND OF REPORTING OF OUTCOMES.
I THINK IT SHOULD BE SOMETHING
SHOULD BE PART OF RECORDING.
>> ONE THING I'VE BEEN THINKING
ABOUT AS WE MOVE TOWARDS BOTH
INVASIVE AND STIMULATE NOT JUST
IN THE LAB BUT POTENTIALLY
WEARABLE STIMULATION THIS
QUESTION OF BEHAVIORAL
ASSESSMENT AND NATURALISTIC
VERSUS LABORATORY BASED BECOME
BURDENING.
WHAT ARE THE CLOSED LOOP AND
REAL WORLD METRICS AND MARKERS
WE WOULD WANT TO BE ACTUALLY
MEASURING GIVEN THAT ULTIMATELY
THAT'S WHERE THE SYMPTOMS APPEAR
AND WHERE THE SYMPTOMS HAVE
EFFECTS ON EVERY DAY LIVES AND
SO CONNECTING OUR LABORATORY
METRICS TO REAL WORLD BEHAVIORS
AND OUTCOMES IS GOING TO BECOME
REALLY IMPORTANT.
>> IT FEELS LIKE RESEARCH ON THE
OBJECTIVES CAN SPLIT AT SOME
LEVEL WITH MECHANISTIC AND HIGH
LEVELS OF CONTROL AND INFERENCES
ABOUT WHAT YOUR SIMULATION IN
THE BRAIN FUNCTION VERSUS
INTERVENTIONAL THINGS.
YOU TALK ABOUT CLOSED LOOP AND
THINGS LIKE THAT.
THAT MAY BE EASY TO IMPLEMENT IN
THE LABORATORY SETTING BUT YOU
HAVE TO HAVE FULL CONTROL OVER
THE INPUTS TO START TO THINK
ABOUT PUTTING TOGETHER A
CLOSED-LOOP SYSTEM.
THIS IS A POINT WHERE IT'S
IMPORTANT TO DO GOAL SETTING IN
TERMS OF THE SCIENTIFIC OR
CLINICAL OBJECTIVES BECAUSE THEY
CONSTRAIN HEAVILY THE METHODS WE
NEED TO USE.
YOU I HAVE ONE LAST QUESTION
RELEVANT TO THE THEMES AND
INTEGRATION WITH THE NON-HUMAN
ANIMAL MODELS.
WHAT ARE PROMISING THINGS PEOPLE
ARE DOING IN THIS SPACE AND THE
CHALLENGES AND ANY KINDS OF
QUESTIONS MORE SUITABLE TO BE
ADDRESSED WITH METHODS THAT ARE
CURRENTLY AVAILABLE?
ANY THINGS THAT ARE HARDER WITH
METHODS TO BE AVAILABLE?
WHAT ARE EFFECTIVE AND
INEFFECTIVE MODELS.
YOU START WITH STIMULATION
PHYSICS.
YOU PUT THE TMS OVER THE HUMAN
OR MOUSE IT WILL GET THE
DIFFERENT FIELD AND ELECTRIC
STIMULA
STIMULATION.
THOSE ARE THINGS THAT MAKE A BIG
DIFFERENCE.
ANIMAL MODELS AND CLOSER TO WHAT
A HUMAN CAN DO MORE TRANSLATION
EFFORTS AND ONE GREAT ADVANTAGE
IS ANIMAL MODELS CAN HAVE A
PRECISE DOSE CONTROL.
YOU DO INVASIVE MEASUREMENTS AND
YOU CAN HAVE A VALUABLE EFFORT
PAUSE THEY CAN COMPARE TO SAY
STIMULATION THAT WE HAVE IN THE
HUMANS.
I'M A BIG FAN OF THE DOSE
CONTROL THAT'S POSSIBLE IN THOSE
ANIMAL MODELS.
>> ONE RELEVANT QUESTION IN
TERMS OF LARGER SCALE EFFORTS IS
HOW TO INCENTIVE IT AS WELL.
WHEN YOU START APPLYING
NON-INVASIVE STIMULATION METHODS
THAT CAN BE USED IN HUMANS FOR
EXAMPLE NON-PRIMATE LEVELS
YOU'RE AT LEVEL COARSER TO WHAT
IS THE CUTTING-EDGE METHOD IN
THE ANIMAL MODEL TO IDENTIFY
QUESTIONS.
HOW DO YOU MOTIVATE PEOPLE TO
ACROSS ACROSS LEVELS AND USELESS
SOPHISTICATED APPROACHES TO
UNDERSTAND WHAT IS HAPPENING IN
THE HUMAN BRAIN?
CORY YOU HAD YOUR HAND UP.
>> ONE QUICK COMMENT.
I THINK IT'S WORTH WHETHER YOU
ARE TALKING ABOUT TEMPORAL
SCALES OR ANIMAL MODELS TO NOT
VEER TOO FAR FROM YOUR INITIAL
STUDY.
AS YOU GO DEEPER AND DEEPER IN
THE ANIMAL MODEL WORK AND WORK
WITH MICE AND OPTOGENETIC
STIMULATION AND TRYING TO RELATE
THAT TO TMS AND EEG IN HUMANS
YOU MAY LOSE THE THREAT A LITTLE
BIT AND THERE'S SO MANY
APPROACHES IT'S DIFFICULT.
IF YOU GO TO NON-HUMAN PRIMATE
AND USE EMS COIL YOU'LL BE ABLE
TO FOLLOW THE THREAT.
SIMILARLY IF YOU LOOK AT SCALP
EEG AND DIVE INTO SINGLE UNIT
RECORDINGS YOU MAY BRING IN THE
INVASIVE WORK IN BETWEEN AND
THAT MAY GET THERE.
ON THE TEMPORAL SCALE TOO IF YOU
LOOK ACUTE EFFECTS OF A SINGLE
SESSION OF DATA BURST FOR THREE
MINUTES AND LOOK AT WHAT HAPPENS
WHAT HAPPENS WITHIN THE FIRST
MINUTE OF TMS AND LONGITUDINAL
RECORDINGS IN PATIENTS WITH
DEPRESSION AND TRYING TO ALIGN
THOSE THREADS, IT'S TRICKY.
YOU NEED TO WALK ALONG SLOWLY
WHICH CAN BE LESS EXCITING
INITIALLY BUT IS REALLY
IMPORTANT.
>> WE JUST GOT A 10 MINUTE
REMAINING WARNING.
I GOT MY CHAT WORKING.
>> WHEN EN YOU DO STIMULATION
AND NON-STIMULATION IN ANIMAL
MODELS MAKES A BIG DIFFERENCE
LITHE THE THICKNESS OF THE SKULL
AND MUSCLE IN THE SKULL.
THERE'S A BIG DIFFERENCE BETWEEN
HUMANS AND PRIMATES AND WORKING
OUT THOSE DIFFERENCES AND WE
HAVE MORE WORK DO.
AND YOU CAN HAVE A GENTLE
MASSAGING OF THE BRAIN AND THE
THICKNESS OF THE SKULL AND
MUSCLES WILL ALL EFFECT BE WHICH
FREQUENCIES YOU GRAB AND THE
EXTENT OF THE STIMULATION.
I GUESS MUCH SAYING MORE WORK TO
DO.
>> I THINK WE ONLY HAVE SO
MINUTES SO WE HAVE A LOT OF
BIGGER PICTURE QUESTIONS AND
MOVE TO LARGE SCALE STUDIES AND
DESIGN.
WE TOUCHED ON THE IDEAS I THINK
IT WOULD BE GOOD TO REVISIT
THEM.
WE TALKED ABOUT A WHOLE LIST OF
THINGS AND ACCOUNTING FOR
INDIVIDUAL DIFFERENCES AND
EFFORTS USED TO TRY TO TRACK
THESE VARIABLES, I'M WONDERING
IF ANYONE WOULD LIKE TO TALK
ABOUT BEST PRACTICES IN TERMS OF
WHAT VARIABLES COULD BE
ACCOUNTED FOR WITH LARGER SCALE
ACROSS SITES AND NON-INVASIVE
BRAIN STIMULATION AND STUDIES.
WHAT ARE THE IMPORTANT THINGS TO
CAPTURE AND ANY THOUGHTS HOW TO
STANDARDIZE IT.
>> THERE'S A BIG DIFFERENCE WITH
THE CLINICAL SETTING WE DO IN
OUR LAB.
I WORRY ABOUT STANDARDIZING DATA
COLLECTION AND PARADIGMS BECAUSE
A LOT OF THEE DISCOVERIES MADE
OVER THE YEARS ARE MADE WITH
INNOVATIVE PARADIGMS AND
STANDARDIZING THE PARADIGM LIKE
YOU PUT BLINDERS ON AND FORCED
DOWN CERTAIN CHANNELS.
AND THAT MAY WORK WORK VERY WELL
IN THE APPROPRIATE OR CLINICAL
SETTING BUT STANDARDIZE TEXTS
ARE COUNTER PRODUCTIVE.
>> IT'S A WONDERFUL POINT THAT'S
COME UP A FEW TIMES.
IT'S GOOD TO HAVE SOME
STANDARDIZED TOOLS PEOPLE CAN
USE IF THEY WANT TO DRAW A
COGNITIVE FUNCTION AND DESPITE
ALL THE VAGRANCIES AND
EXPERIMENTAL GOALS HOW DO WE PUT
DATA IN A FORMAT TO ALLOW IT TO
BE AGGREGATED IN THE FUTURE AND
ANALYZED IN A WAY BEYOND OUR
LABORATORIES.
>> AND THAT STANDARDIZING TOOL
KITS FOR DATA AND WE CAN DO ALL
THAT.
THE EXPERIMENTAL DESIGN IS WHERE
I GET WORRIED.
>> THERE'S MODELS IN THE NEURO
IMAGING FIELD AND IT WOULD BE
GREAT TO HAVE IDEAS AND LOOK AT
FOR
FORMATS.
>> MAKE SOFTWARE TOOLS AVAILABLE
TO THE COMMUNITY AND MAKE IT
EASY TO USE.
ELECTRIC MODELS HAS TO COME AS A
STANDARD TOOL THAT'S BEEN NOW
USED AND BASICALLY MANY NOT ALL
NON-INVASIVE BRAIN STIMULATION
STUDIES AND THE TOOLS BECOME SO
EASY TO USE AND YOU DOWNLOAD
YOUR DATA TO THAT.
THERE'S INTEGRATION AND OTHER
IMAGING DATA AND CREATING NEW
STANDARDS FOR EXAMPLE I THINK
MAKING IT EASY TO EVERYONE CAN
USE THAT.
I THINK YOU CAN USE THAT IN THE
FIELD.
>> BRUCE.
>> IT'S HARD TO KNOW WHAT YOU'RE
STIMULATING AND THE OBVIOUS
THINGS WE TALKED ABOUT DOSING
AND TARGETING.
THERE'S VERY SIMPLE THINGS THAT
COULD BE STANDARDIZED THAT
PROBABLY SHOULD BE THOSE ARE A
COUPLE OF EXAMPLES.
>> LESSONS LEARNED FROM PREVIOUS
LARGE SCALE EFFORTS I THINK
THESE ARE A BROAD SPACE TO
CONSIDER BUT ALONG THE IDEA OF
THE INCENTIVE STRUCTURES TO
CREATE A LARGE SCALE EFFORT.
WE TALKED ABOUT THE IDEA THERE'S
INCENTIVES FOR OTHER PURPOSES
AND WE'LL ALL TRY TO ADDRESS THE
SAME THING AND HARMONIZE ACROSS
LABS.
AND INTERESTING TO THINK ABOUT
WHAT ARE THE INCENTIVES AND
CHALLENGES.
>> WE'RE TOLD FROM NOW ON ALL
OUR DATA HAS TO BE SHARED AND ON
THE VARIOUS PLATFORMS AT THE NIH
AND HAVE A FEELING THE
INCENTIVIZATION IF YOU WANT A
GRANT OR NOT THE DATA HAS FOR
SHARED MAY SOLVE ITSELF.
>> THERE'S A NEED TO WORK OUT
HOW TO MAKE IT USEFUL.
I DON'T KNOW HOW MANY HAVE TRADE
TO PULL DATA FROM OTHER STUDIES
TO RE-ANALYZE THEM.
I HAVE NOT BECAUSE IT'S A
TREMENDOUS CONFUSING HEADACHE TO
DO SO.
THERE'S CONSENSUS ON THE DATA TO
AGREE ON SOME STRUCTURE FOR
WHAT'S GOING TO GET SHARED AND
HOW TO MAKE IT USABLE WITHOUT AN
EXCESSIVE AMOUNT OF HAND HOLDING
OF THE PEOPLE WHO CREATED THE
DATA WHICH IS COMMON AND YOU
BETTER GET COMFORTABLE WITH
WHOEVER COLLECTED THE DATA.
>> FOR THE TMS, EMG FIELD SO
THERE'S AN INTERNATIONAL
CONSORTIUM WHERE WE TRIED TO
ESTABLISH AND HAS OVER 30 LABS
AROUND THE WORLD SO TO DO THE
STUDY WHERE WE WOULD ALL DO THE
SAME THING THOUGH WE HAVE
SLIGHTLY DIFFERENT DEVICES AND
LOOK AT THE RESULTS.
THEN THE START OF THE STUDY HAS
BEEN DELAYED BECAUSE OF
INTERNATIONAL -- WE ALL HAVE
DIFFERENT HIPAA RULES AND ALSO
AND WHAT IS IDENTIFIABLE DATA.
SO SOME IRB'S ARGUE THAT EEG'S
ARE IDENTIFIABLE AND IT'S NOT
REALLY CONSENSUS IN THEORY WITH
THE MACHINE LEARNING THINGS YOU
COULD IDENTIFY EVERYTHING AND
THEN LIKE THAT HAS SLOWED DOWN
TMS IS CONSIDERED NON-INVASIVE
AND IN EUROPE THEY'RE TRYING TO
CHARGE THE CLASSIFICATIONS SO
THAT TMS WOULD BE THE SAME RISK
LEVEL AS INVASIVE STIMULATION
AND INTERNATIONAL
COLLABORATIONS.
>> EXCELLENT POINT.
ALEC WIDGE SAID THAT'S RED TAPE
THAT NEEDS CUTTING WITH DATA
SHARING AND IT NEEDS TO BE
SHARED AND HELP MOTIVATE
INSTITUTIONS TO DO SO AT SOME
LEVEL.
THERE'S A COMMENT IN THE CHAT
AND SAMPLE SIZE IS THE
PRECONDITION FOR SOME TOPICS.
>> IT'S OBVIOUS.
YOU NEED MORE THAN SAMPLE SIZE
BUT IT'S A PLARGE SAMPLE SIZE
THAT'S CRUCIAL.
>> THIS IS A COMMENT YOU BROUGHT
UP BEFORE THE MEETING AS WELL
WHICH IS THE QUESTION ABOUT ARE
THERE DATA FROM NON-INVASIVE
BRAIN STIMULATION OR STIMULATION
IN GENERAL TO HELP MOTIVATE
CONSIDERATION OF EFFECT SIZE AND
EXPERIMENT DESIGN.
THAT THE A REALLY INTERESTING
QUESTION.
I THINK THERE ARE A TON MY TAKE
IS THERE'S SMALL END STUDIES OUT
THERE THAT AND THERE MAY BE WORK
IN EXISTING DATA TO THEN HAVE A
DECENT SAMPLE TO ESTIMATE EFFECT
SIZE FOR EXPERIMENT DESIGN IS A
QUESTION
>> AND MORE DIVERSE SAMPLES WILL
BE MORE DIVERSE IN DIFFERENT
WAYS GOING BACK TO THE
INDIVIDUAL DIFFERENCES AND
ACCOUNTING FOR THAT WILL BE IF
THOSE COULD TEND TO WASH OUT
EFFECT SIZES IN SMALLER,
TARGETED STUDIES TO SOME EXTENT.
>> FOR SOME INVASIVE STIMULATION
STUDIES IT CAN GET IN THE SINGLE
DIGITS.
MAYBE THAT'S OKAY.
EARL, YOU'RE ON HERE AND YOUR
SAMPLE SIZES ARE ONE OR TWO.
IS THERE A TENSION BETWEEN
GETTING A LOT OF DATA FROM A
SMALL NUMBER OF SUBJECTS THAT
ARE HIGHLY REPUBLLICABLE VERSUS
OTHER SUBJECTS?
>> THAT'S THE NATURE OF OUR
MEASURES.
WE DO OBSERVATION SPACED OUT
OVER TIME IN HUGE NUMBERS OF
SUBJECTS RATHER WE CAN'T EVEN
APPROACH THOSE QUESTIONS IN
NON-HUMAN PRIMATES BUT IT'S
SPACED OUT.
>> WE HAVE PEOPLE COMING IN LIKE
MIKE AND SHAN WERE TALKING ABOUT
FOR MANY WEEKS OF STIMULATION
EVERY DAY AND MAY BE POSSIBLE TO
LOOK AT INDIVIDUAL REPLICABILITY
OVER MANY SESSIONS OF SOME OF
THE VARIABLES.
>> IT'S A WONDERFUL CONVERSATION
BUT WE'RE RUNNING ABOUT THREE
MINUTES OVER.
I WANT TO SAY SOMETHING REAL
QUICK AND TURN IT OVER TO
CLAYTON.
>> I JUST WANTED TO THANK THE
ORGANIZATION AND TAKING THE
NEBULOUS IDEAS AND TURNING THEM
INTO LOTS OF TOPICS FOR
CONVERSATIONS THE LAST FEW DAYS.
IT'S BEEN EXCITING AND
MOTIVATING.
THIS IS THE LAST SESSION AND
HAVE A SLIDE SO I GET TO HAVE
THE FINAL MEME TO END.
I HOPE IT'S MOTIVATING.
>> THANK YOU, JOEL, AARON AND
YOU WILL OF YOU FOR A GREAT
SESSION.
IT'S BEEN FANTASTIC.
WE STARTED OFF WITH A BANG AND
FORTUNATE TO CLOSE WITH ANOTHER
BANG.
SO HERE TO OFFER HIS REMARKS IS
THE DIRECTOR OF THE NIH BRAIN
INITIATIVE, DR. JOHN NGAI
BECAUSE EVERYONE KNOWS WHO HE IS
I'M GOING TO FIGHT BACK MY
TEMPTATION TO LAUNCH INTO
PERSONAL ACCOMPLISHMENTS AND SAY
HOW GRATEFUL WE ARE FOR HIS
VISIONARY LEADERSHIP AT THE
BRAIN INITIATIVE AND AFTER HIS
REMARKS I'LL BE BACK TO POINT
EVERYONE TO IMPORTANT RESOURCES
FOR KEEPING THE CONVERSATIONS
FROM TODAY AND YESTERDAY MOVING
FORWARD.
DR. NGAI.
>> THANKS, CLAYTON.
THANK YOU, BONNIE, ANDREW AND
EVERYONE ON THE PLANNING EQUITY
AND OUR COLLEAGUES AT ROSE LEE &
ASSOCIATES FOR PUTTING TOGETHER
THE WORKSHOP.
WE HEARD ENTHUSIASM INVOLVING
STIMULATION AND RECORDING IN
HUM
HUMANS WHICH IS A COOL IDEA AND
WE HEARD GOOD THOUGHT DISCUSSION
ON QUESTIONS AND CHALLENGES THAT
NEED THOROUGH CONSIDERATION TO
INFORM SUCH COORDINATED EFFORT
SUCH AS THE NEED FOR MORE
STANDARDIZED WAYS OF
UNDERSTANDING THE EFFECTS OF
STIMULATION AND WHETHER IT'S ON
ASSAYS OR TESTS OR DATA IS
SOMETHING THAT WILL HAVE TO
UNFOLD OVER TIME.
AND HEARING FROM THE STIMULATION
EXPERT THE THEME EMERGED
CONVERGENT CAUSES OF INFORMATION
CAN INFORM STIMULATION TARGETS
AND NETWORKS OF BEHAVIORAL
FUNCTION AND DYSFUNCTION.
FROM THE BEHAVIORAL SESSION WE
HEARD HOW TESTS ARE CHOSEN AND
INNOVATION STUDIES AND WHAT
CONVERSATIONS ARE NEEDED GOING
FORWARD DURING THE LEVELS OF
EXPLANATION SESSION WE HEARD
DYNAMICS AND THE IMPACT OF
DYNAMIC SYSTEMS AND SEEMS THE
FIELD IS READY TO TAKE ON
DYNAMICS MORE AGGRESSIVELY AND
HEARD COORDINATED EFFORT MAY BE
ABLE TO FACILITATE DIFFERENT
LEVELS OF EXPLANATION OF
COGNITION NOT JUST THE DATA
AGGREGATION FOUL WITH ARTIFICIAL
INTELLIGENCE AND ALGORITHMS ARE
EXCITING.
CONVERSATIONS DURING THE MODEL
SYSTEM ENFORCE THE NEED FOR
STRONG COLLABORATION BETWEEN
EXPERIMENTAL AND MODELLING
EXPERTESE FROM THE BEGINNING AND
LOOKING AT DIFFERENT MODELS AND
NEW OPPORTUNITIES FOR UNCOVER
INSIGHTS ON FUNDAMENTAL BEHAVIOR
AND CLINICAL OUTCOMES.
AND AT AN OPERATIONAL LEVEL
FINDING PATHS TOWARDS COMMON
METADATA STANDARD AND LEVERAGE
THE APPRECIATION DATA RESOURCES
TO CREATE TRUE KNOWLEDGE BASES
FOR BROADER BENEFIT.
AND STRESS THE IMPORTANCE OF
EMBEDDING THEORY WITH
EXPERIMENT.
THIS IS SOMETHING THAT CANNOT BE
OVERSTATED.
ANOTHER RECURRING THEME
THROUGHOUT HAS BEEN
UNDERSTANDING AND ACCOUNTING FOR
INDIVIDUAL VARIABILITY AND
POPULATION HETEROGENEITY.
STUDY DESIGN CONSIDERATIONS
WHETHER THE GOAL IS TO
UNDERSTAND BRAIN FUNCTIONS
ACROSS INDIVIDUALS OR UNDERSTAND
POPULATION HETEROGENEITY WITHIN
PEOPLE.
THE DISCUSSION FROM THE LAST TWO
PANELS HAVE BEEN GREAT AND
HELPED CRYSTALIZE THE CONCEPT
AND PLACE THEM IN THE PRACTICAL
CONTEXT OF WORKING ON AND WITH
ACTUAL HUMANS AND HOW TO
MAXIMIZE THE DATA OF THEIR
PARTICIPATION.
AND WHEN IT COMES TO STIMULATION
AND PERTURBATION IN HUMANS ONLY
ETHICAL CONSIDERATIONS FOR
VULNERABLE POPULATION AND KEEP
FRONT AND CENTER THESE ARE
PEOPLE LIVES AND LOOK AT SAFETY
AND THE ISSUES INCLUDE BUT NOT
LIMITED TO DIVERSITY OF STUDY
COHORTS TO MAXIMIZE THE UTILITY
AND GENERALIZABILITY OF THE
STUDIES.
DATA PRIVACY AND RISKS OF
RE-IDENTIFICATION IN LIGHT OF
RAPID ADVANCES OF DATA
TECHNOLOGY AND DATA OWNERSHIP
AND LONGEVITY AND ACCESSIBILITY
AND WITH ALL THE CONSIDERATIONS
IN MIND STRATEGIES FOR MORE
EFFECTIVE DATA TO MAXIMIZE VALUE
OF OUR RESEARCH SUBJECTS'
PARTICIPATE.
SO ON BEHALF OF THE BRAIN
INITIATIVE THANK YOU TO THE
PARTICIPANTS FOR WHAT COULD BE
THE NEXT EXCITING OPPORTUNITIES
IN HUMANS TO ALLOW US TO UNRAVEL
CORE PRINCIPLES OF THE BIOLOGY
THAT UNDER LIES HUMAN BEHAVIOR
AND ENCOURAGE YOU TO THINK OF
BUILDING COLLABORATIONS AN
CONSORTIA TO LEVERAGE DIVERSE
EXPERTISE AND THOSE OF THE
RESEARCH PARTICIPANTS THEMSELVES
TO PURSUE AND CRATE UNIQUE
OPPORTUNITIES TO STUDY THE
LIVING HUMAN BRAIN WITH RAPIDLY
GROWING TECHNOLOGIES.
BACK TO CLAYTON.
>> THANK YOU.
THIS CONCLUDES OR FORMAL AGENDA
I WANT TO DOUBLE DOWN AND DIRECT
EVERYONE TO THE REQUEST FOR
INFORMATION THAT IS NOW OPEN.
IT WILL REMAIN OPEN TO AUGUST 1.
WE'RE INTERESTED IN THE DIVERSE
PERSPECTIVE BES OF ALL COMMUNITY
MEMBERS AND STAKEHOLDERS WHO
HAVE SOMETHING TO SAY ABOUT THE
OPPORTUNITIES AND CHALLENGES FOR
COORDINATED EFFORTS TO ADVANCE
THROUGH NEURAL STIMULATION
RECORDING.
LASTLY ON BEHALF OF THE NIH
PLANNING COMMITTEE I WANT TO
EXTEND A SINCERE THANK YOU TO
ALL WHO CONTRIBUTED TO THE
WORKSHOP AND OUR WONDERFUL
CHAIRS AND ANALYSTS AND HAVEN'T
CONTRACTOR, ROSE LEE&ASSOCIATES
AND THE FOLKS AT NIH MANAGEMENT
WHO SET UP OUR SIMULTANEOUS
VIDEOCAST.
WE CAN'T EXPRESS ENOUGH
GRATITUDE FOR THE TIME, ENERGY
AND BRAIN POWER THAT'S COME
TOGETHER TO MAKE THE MEETING
HAPPEN.
THREW ALL AND WE LOOK FORWARD TO
LEARNING FROM YOUR RFI
RESPONSES.