>>GOOD MORNING
>>WELL, THANK YOU VERY MUCH FOR
THE INVITATION TO SPEAK TODAY.
I AM REALLY HAPPY TO BE HERE AT
SUCH A WONDERFUL VENUE.
I WILL TALK TO YOU TODAY ABOUT
THE WORK WE'VE BEEN DOING FOR
THE LAST 2 CAREERS, BUILDING UP
TO SOMETHING I THINK WILL BE
VERY EXCITING, FOR PRECISION
DOSING, CUSTOM DOSING AND
INVESTIGATE MECHANISM IMAGING,
TRIAL DATA, SO, YOU'VE HEARD BY
THIS POINT AT THE CONFERENCE
ABOUT WHAT IS TDS, I DON'T HAVE
TO LABOR THIS SLIDE.
TDCS, SHOWS A LOT OF PROMISE, IT
GENERATES 1-2-AMPS TO THE FIELD
TO TISSUE, LOTS OF POTENTIAL
APPLICATIONS, LOTS OF POTENTIAL
PROMISE BUT I WILL ARGUE THAT
THE FULL PROMISE OF THIS
TECHNIQUE IS FAR FROM REALIZED
AND THERE'S WORK WE CAN DO TO
GET THERE SO WHAT ARE THE
CHALLENGES PREVENTING US FROM
REALIZING THIS PROMISE OF THIS
TECHNIQUE?
WELL LIKE ANY METHOD OF
TREATMENT, INTERVENTION OR WHAT
HAVE YOU, THERE'S VARIABILITY IN
THE RESPONSE.
NOW THAT IS TO BE EXPECTED.
NOT ALL PHARMACEUTICALS ARE
EFFECTIVE, NOT ALL BRAIN
STIMULATORS ARE EFFECTIVE IN
EVERY PERSON, FINE.
BUT THERE ARE REASONS WHY IT'S
NOT EFFECTIVE IN INDIVIDUALS AND
WE NEED TO UNDERSTAND THAT
BETTER.
SOME OF THE KEY CHARACTERISTICS
WE KNOW PLAY A ROLE IN THIS
INVOLVE CURRENT DOSE.
SO WE WOULD ARGUE THAT'S A KEY
PLAYER.
HOW MUCH CURRENT WE PUT INTO THE
BRAIN AND WHERE WE PUT IT IN THE
BRAIN HAS AN IMPACT ON THE
EFFICACY ON THE STIMULATION OF
THE TREATMENTS.
YOU HEARD COMMENTS EARLIER IN
THE CONFERENCE THAT ARE CHANGING
THE FIELD REGARDING IN VIVO
MEASURES WHICH ARE INCREDIBLY
IMPORTANT TO PROGRESS AT
PRESIDENT THOUGH, IT HAS BEEN
FOR MRI DERIVED MODELS THAT CAN
AT LEAST GIVE US A CLEAR
ESTIMATE OF CURRENT AND CURRENT
DELIVERY IN THE BRAIN, BUT I
WOULD SAY, OUR BIGGEST CHALLENGE
IN THIS FIELD THUS FAR IS THE
CONTINUED RELIANCE ON A 1 DOSE
FITS ALL MODEL MEANING THAT IN A
PARTICULAR STUDY, PARTICIPANTS
RECEIVED THE SAME DOSE ACROSS
ALL PARTICIPANTS, 2 MILLI AMPS
FOR A SPECIFIC LOITION, SPECIFIC
AMOUNT OF TIME, ET CETERA.
ET CETERA.
NOW WERE WE TO TAKE YOUR
FAVORITE BLOOD PRESSURE
MEDICATION AND APPLY IT TO THE
SAME DOSE IRRESPECTIVE OF THE
SAME PERSON, YOU CAN IMAGINE HOW
MUCH EFFICACY WOULD DECREASE, IF
YOU DIDN'T TAKE INTO,A COUNT
METABOLIC STATE, HEIGHT, WEIGHT,
ET CETERA, ET CETERA.
WELL IT URN ITS OUT WE CAN DO
SOMETHING VERY SIMILAR TO THAT,
USING IMAGING AND MODELING AND
OTHER METHODS TO ATTEMPT TO
CUSTOMIZE OUR DOSE, TAKE
SOMETHING THAT'S DOSED OR NEAR
PRECISELY DOSED AND IMAGINE THE
DIFFERENCE IN EFFICACY, I THINK
THOSE CAN BE QUITE BIG.
WE DON'T KNOW YET BUT THAT'S THE
WORK WE'RE TRYING TO ACHIEVE.
NOW WHAT ARE SOME OF OUR BIGGEST
PROBLEMS WE KNOW?
WE KNOW THAT EVERY BRAIN IS
UNIQUE, IT IS A FINGERPRINT.
WHILE IT IS SIMILAR, IT IS
SUBTLEY DIFFERENT, WE ALSO KNOW
AS WE AGE BRAIN CHANGES IN WAYS
THAT VERY WELL CLASSIFIED OVER
THE LAST FEW DECADES.
AT THIS BOTTOM, YOU CAN SEE A
FIGURE EXTRACTED FROM 1 OF OUR
PAPERS IN 2019 THAT RESTATES
WHAT'S BEEN SHOWN SINCE THE
ADVENT OF MRI, THAT THERE ARE
CHANGES IN THE WHOLE BRAIN
LEVEL, IN GRAY MATTER THAT
HAPPEN OVER THE LIFE SPAN BUT AT
THE WHOLE BRAIN LEVEL, WHITE
MATTER IS A BIT MORE STABLE, YET
IF YOU MOVE TO THE TOP OF THE
SCREEN, YOU SEE HERE AN EXAMPLE
OF THESE 3-CENTIMETER ROIs
FROM ANTERIOR VERSUS POST ERIOR
REGIONS, AND IF YOU LOOK OVER TO
THE LEFT, YOU SEE VERY DIFFERENT
PATTERNS OF CHANGE PARTICULARLY
IN THE WHITE MATTER WHICH IS IN
BLUE DEPENDING ON WHERE YOU ARE
IN THE BRAIN.
SO THIS MEANS THERE ARE REGION
SPECIFIC DEFENSES IMPACTED BY
AGE.
AND WE'VE DONE STUDIES AND I
WILL SHOW YOU THESE IN A FEW
SLIDES, THAT DEMONSTRATE THE
POTENTIAL IMPACT OF ATROPHY
ALONE MUCH LESS INDIVIDUAL
VARIABILITY OF OTHER LEVELS
RELATIVE TO DIFFERENCES IN
ADIPOSE TISSUE, DIFFERENCE IN
SKULL THICKNESS, ET CETERA THAT
CAN IMPACT HOW MUCH CURRENT
REACHES THE BRAIN AND WHERE THAT
CURRENT GOES.
NOW HOW DO WE DERIVE THIS
INFORMATION?
I TALKED ABOUT THIS A BIT.
THERE ARE NEWER MOTHERS FOR IN
VIVO MEASUREMENT THAT ARE VERY
EXCITING BUT OUR STANDARD HAS
BEEN USING THESE FINITE ELEMENT
COMPUTATIONAL MODELING, IN THIS
CASE, T1 WEIGHTED IMAGES AND IN
THE PAST, 15 YEARS AGO, THIS WAS
NOT A VERY ACCESSIBLE TECHNIQUE
BUT WITH THE ADVENT OF WONDERFUL
OPEN ACCESS SOFTWARE LIKE SIM
NIBS OR ROAST, THIS IS A MUCH
MORE ACCESSIBLE TOOL FOR BASIC
MODELING APPROACHES AND WITH
THIS INCREASE IN ACCESSIBILITY,
WE HAVE POTENTIAL FOR DOING
INDIVIDUAL MODELS IN MUCH LARGER
POPULATION, MUCH MORE QUICKLY
THAN IN THE PAST WHERE A SINGLE
BRAIN MIGHT TAKE 6 WEEKS FROM
FROM AN EXPERT SEGMENTER TO GET
A SINGLE MODEL WE CAN DO THESE
IN MUCH, MUCH ISSUES FASTER
TIMES WITHIN THE SAME DAY THAT
THE PARTICIPANT COMES INTO THE
CLINIC OR THE LAB.
BUT FOR US MORE IMPORTANTLY
THESE TYPES OF MODELS GIVE US
INSIGHT INTO DIFFERENCES BETWEEN
BRAINS WHICH WE THINK AS I SAID
IS VERY IMPORTANT.
NOW THIS IS A MASSIVE
EVERYSIMPLIFICATION OF THE
PIPELINE THAT INVOLVE SAYS T1
WEIGHTED IMAGE AT A MINIMUM,
VOLUME MESSAGING, FINITE AND
ESTIMATE OF CURRENT DENSITY
DISTRIBUTION.
THIS IS A STUDY THAT WAS LED BY
A FORMER POST DOC IN MY LAB AND
NOW A BRILLIANT POST DOC,OOSE A
CITY FROM 587 OLDER ADULTS WITH
IMAGES AND IMAGES FROM THE
STUDY.
THE GOAL WAS TO EVALUATE HOW AGE
AND ATROPHY IMPACT CURRENT
DENSITY DISTRIBUTION USING A FEW
MODIFICATIONS, ANDLET MORE
CLASSIC M1 SO MONTAGE IN THE
LITERATURE.
NOW TO THE EYE, YOU CAN SEE
CHANGES AS WE MOVE THROUGH THE
DECADES OF LIFE, THAT ARE EVEN
OBVIOUS AT THIS POINT.
BUT WHEN WE MOVE TO EVALUATE
THESE AT A LARGER LEVEL, WE CAN
ACTUALLY SEE THESE TRAJECTORIES
OF CHANGE AND REALLY WHAT THIS
FIGURE SHOWS, IS THAT AS BRAIN
ATROPHY INCREASES, CURRENT
DENSITY DELIVERED TO THE BRAIN
DECREASES AND THE LARGE PART OF
THAT IS AN INCREASED AMOUNT OF
CSF WHICH DISTRIBUTES CURRENT
VERY WELL ACROSS THE BRAIN BUT
DISTRIBUTES IT IN A WAY
TAKEN--THEY DILUTES THE OVERAWE
DENSITY DELIVERED TO THE TISSUE
IN ADDITION TO ITS DEPTH.
SO THESE FACTORS ALONE CAN
IMPACT.
THERE'S ALSO SO MANY INDIVIDUAL
VARIABILITY COMOPPOSITE
BEHAVIORIAL PHENOTYPENTS AS I
MENTIONED REGARDING ADIPOSE
TISSUE, FATTY TISSUE ON THE HEAD
AS WELL AS DIFFERENT TYPES OF
BONE, CANC CELLUS AND
NONCANCELUS, SO WE HAVE THESE
DIFFERENT COMPONENTS.
TURNS OUT OUT WE CAN ESTIMATE
THOSE USING COMPUTATIONAL
MODELS, AND IF WE CAN ESTIMATE
THOSE THEN WE CAN ASK, THEY THEY
PREDICT BEHAVIOR?
CAN THEY PREDICT CHANGES IN THE
BRAIN AND I'LL ARGUE THAT IF
THEY CAN, THERE MAY BE VALUE IN
PREDICTING OTHER COMPONENTS LIKE
RESPONSE.
SO LET'S DO A USE CASE AND IN A
FORMER STUDY WE RAN AND A
GRADUATE STUDENT OF MY NICONTROL
NEESOME PUBLISHED IN 2019
INVOLVED A TDS STUDY LOOKING AT
APPLICATIONS OF TDCS OVER F3 AND
F4 AT 2 MILLI AMPS IN THE MRI
ENVIRONMENT BEFORE, DURING
AND--DURING ACTUAL PERFORMANCE
OF A WORKING MEMORY TASK.
AND WE MEASURED THIS WORKING
MEMORY TASK FUNCTIONAL
ACTIVATION, BEFORE, DURING AND
AFTER EITHER ACTIVE STIMULATION
OR SHAM STIMULATION WITH A 2
WEEK WASH OUT PERIOD.
IN THIS, WHAT WE FOUND IN THAT
PRIME STUDY IS AN INCREASE IN
CONNECTIVITY FROM LEFT TO VLPC
TO DURING STIMULATION VERSUS
BEFORE OR AFTER DISP WHAT WE ASK
IN THIS STUDY, AGAIN LED BY THE
DOCTOR, IS WHETHER OR NOT WITH A
HYPER SEGMENTED MODEL OF 10
TISSUE TYPES, THIS WAS ACTUALLY
A HIGH FIDELITY MODELING
APPROACH THAT IS OUTSIDE OF
ROAST OR SIM NIB OR OTHER
SOFTWARES USING MORE CLASSIC
TECHNIQUES AND WHAT WE ATTEMPTED
TO TO DO WAS TO CREATE THE BEST
OVERALL MODEL POSSIBLE IN AN
ATTEMPT TO PREDICT THOSE
CURRENT, THOSE CHANGES IN BETA
VALUES OR FUNCTIONAL
CONNECTIVITY BETWEEN THESE 2
REGIONS IN THE SAMPLE AND HERE
YOU CAN SEE WE WERE RABBLE TO
ESTIMATE FROM THE MRIsS EXACT
POSITIONING OF THE ELECTRODES,
WE ACTUALLY THINK THESE SUBTLE
DIFFERENCES AND ELECTRODE
PLACEMENTS CAN PLAY A MAJOR ROLE
IN OUR ABILITY TO ACCURATELY
REDICT WHAT THE CURRENT IS DOING
AND WHAT IT'S RELATED TO.
AND THESE 15 PARTICIPANTS, YOU
CAN SEE HERE OUR OVERALL
ELECTRIC FIELD DISTRIBUTION.
YOU CAN SEE TOLET EYE THE
SOWBTLE DIFFERENCES BETWEEN EACH
THESE INDIVIDUALS, HERE YOU GET
THE CURRENT DENSITY DISTRIBUTION
PATTERN AGAIN CROSS THESE 15
PARTICIPANTS EVEN TO THE EYE,
YOU CAN SEE THESE ARE NOT 1 AND
THE SAME.
WHICH FOR A ONE-SIZE-FITS-ALL
MODEL THEY NEED TO BE 1 AND THE
SAME.
BUT NOT SURPRISING THEY ARE IN
FACT, DIFFERENT.
MORE IMPORTANTLY I WILL ARGUE
THESE APPROACHES CAN GIVE US
INSIGHT INTEREST WHAT TACTUALLY
IN THE BRAIN IS CHANGING THAT
RELATES TO THE OVERALL
BEHAVIORIAL OR OTHER CHANGES
WE'RE MEASURING FROM TDCS, IN
THIS CASE, TO BREAK DOWN THESE
MEASURES VERY QUICKLY FOR THE
SAKE OF TIME, WE FOUND THE
CURRENT DENSITY IN THE LEFT
DLPC, BUT NOT THE LEFT VLPC WERE
SIGNIFICANTLY ASSOCIATED WITH
THE BETA VALUE CHAIMPLES IN
FUNCTIONAL CONNECTIVITY BETWEEN
THESE 2 LOCATIONS MEANING THAT
THE CURRENT DENSITY IN DLPFC WAS
ASSOCIATED WITH CHANGE AND THIS
APPEARS TO JUST BE DRIVING THE
CHANGE FUNCTIONAL CONNECTIVITY
OVERALL VERSUS CURRENT DENSITY
IN THE VLPFC, WHICH IS EXCITING
BUT MORE IMPORTANTLY FOR MY
TALK, IT SHOWS THAT THESE VALUES
CAN PREDICT CHANGES IN THE BRAIN
AND WE'VE SHOWN SEPARATELY
PREDICT CHANGES IN BEHAVIOR.
SO THERE'S POTENTIAL VALUE HERE.
NOW THIS IS WHERE WE INTRODUCED
THE APPLICATION OF DIFFERENT AI
APPROACHES.
IN THIS CASE I WILL TALK ABOUT
MACHINE LEARNING AND LATER I
WILL TALK ABOUT SINGLE AND
MULTIVARIANT GALSIAN FITTING
USING OTHER APPROACHES BUT AT
THE END OF THE DAY WE WENT IN A
DIFFERENT DIRECTION FOR AI FOR A
REASON AND WE'RE DEALING WITH A
MULTIVARIANT DATA STRUCTURE THAT
IS HYPER COMPLEX, YOU HAVE
CURRENT DENSITY IN 3 DIMENSIONS,
X, Y, Z SPECIAL WE HAVE
DIRECTION AND INTENSITY OF
CURRENT.
THAT VECTOR INFORMATION IS
COMPLEX, IT IS ALSO THROUGHOUT
THE BRAIN AND WE HAVE A FOURTH
DIMENSION OF INFORMATION WHICH
IS TREATMENT RESPONSE.
SO WHEN YOU HAVE HYPER COMPLEX
DATA, STANDARD ANALYTICAL
APPROACHES WORK FAIRLY POORLY.
IN ADDITION, IN A CASE WHERE YOU
UNDERSTAND MECHANISM FROM A DATA
PROVIDING NOVEL INSIGHTS INTO
THE OVERALL REASONS THAT THESE
TREATMENT RESPONSES ARE THERE.
AND SO WE CHOSE TO GO IN THIS
DIRECTION EXPW TO DO THIS, WE
TOOK AS PROOF OF PRINCIPLE DATA
FROM ANOTHER 1 OF OUR RECENT
TRIALS, WELL, RECENT AT THE
TIME, 2019, AGAIN, THIS WAS A 28
PERSON COGNITIVE TRAINING TRIAL
IN OLDER ADULTS WHERE THIS PILOT
TRIAL LOOKED AT COGNITIVE
TRAINING PAIRED WITH TDCS, OR
SHAM FOR A 10 DAY PERIOD.
WE MEASURED PREAND POST CHANGES
IN WORKING MEMORY AND FUNCTIONAL
ACTIVITY AND A VARIETY OF OTHER
MEASURES.
IN THIS CASE, WE SAW NICE CHANGE
IN WORKING MEMORY PERFORMANCE ON
A 2 BACK TARGET ACCURACY FOR 1
OF OUR OUTCOME TASKS AND FOR
THIS WE THEN SEGMENTED EACH
BRAIN INDIVIDUALLY ACROSS EACH
SESSION AND PERFORMED THESE SAME
BASIC ANALYTICS TO DERIVE THESE
FINITE MODELS ACROSS ALL
PARTICIPANTS THAT RECEIVE
STIMULATION AND THEN APPLYING
MACHINE LEARNING APPROACHES, SO
IN THIS CASE, SUPPORT MACHINE
VECTOR APPROACHES, WE TEND TO
ASK THE QUESTION OF WHICH
PATTERNS OF CURRENT DENSITY
ACROSS THE PARTICIPANTS
RECEIVING ACTIVE STIMULATION
WERE MOST STRONGLY ASSOCIATED
WITH TREATMENT RESPONSE SO
CHANGE IN WORKING MEMORY
PERFORMANCE AND SO WITH THIS,
THESE AMALSIS PRODUCED A MODEL
THAT OVERALL IN THE SMALL SAMPLE
AND WE WERE USING 10 K FOLD
ACROSS VALIDATION BECAUSE OF THE
SMALL SAMPLE SIZE AND 86%
RACKERACY AND AUC OF 80% BUT
THAT'S NOT PERFECT BUT IN A
SMALL SAMPLE SIZE THAT SHOWS
PROMISE.
WE NEED LARGER DATA TO REALLY
DRIVE THROUGH, BUT IMPORTANTLY,
THERE'S INFORMATION, IN ADDITION
TO THE FACT THAT WE CAN REDICT
FROM A T1 WEIGHTED IMAGE WHO
RESPONDED TO TREATMENT VERSUS
NOT, WE CAN ALSO GAIN INSIGHT
INTO THESE REGIONS THAT WERE
IDENTIFIED AS BEING THE BEST
PREDICTORS OF TREATMENT RESPONSE
VERSUS TREATMENT NONRESPONSE AND
GAIN INSIGHT INTO WHAT'S
HAPPENING OR WHAT'S BEING
DELIVERED TO THOSE PARTICULAR
REAMINGIONS.
AND WHAT WE FIND WHEN WE
INVESTIGATE THIS, IS THAT BY AND
LARGE WHEN YOU LOOK AT THE
RESPONDER PROFILE VERSUS
NONRESPONDER PROFILE, THOSE ARE
THE RESPONDERS IN THESE REGIONS
THAT BEST PREDICTED TREATMENT
RESPONSE, WE'RE SEEING MORE
CURRENT WITHIN THESE REGIONS,
THAN THE NONRESPONDERS.
NOW THIS IS FROM A PAPER LED BY
1 OF MY GRADUATE STUDENTS IN A
COLLABORATION ACROSS A LAB AND
BY O MEDICAL ENGINEERING LED BY
[INDISCERNIBLE] AND BY ME AND
DR. [INDISCERNIBLE].
THIS ACTUALLY GAVE US SOME
REALLY NICE INSIGHT INTO THESE
CHARACTERISTICS, GREAT,
WONDERFUL, MORE CURRENT IN THESE
REGIONS IS BETTER.
YEAH, PROTEIN COMPLEX NOT MORE
SURPRISING BUT WE ALSO ARGUE
THAT MORE CURRENT IS NOT
NECESSARILY ALWAYS BETTER, IT'S
JUST DIFFERENT AND WE NEED TO
HAPPENED WHAT THE CURRENT IS
DOING.
NOW WHAT'S REALLY IMPORTANT IS
WE KNOW WHERE IT WAS SUPPOSEDLY
IMPORTANT AND WE KNOW HOW MUCH
CURRENT IS SUPPOSEDLY IMPORTANT
FOR TREATMENT RESPONSE IN THIS
PARADIGM AND IF WE KNOW THOSE
THINGS, WE'RE 1 STEP OFF FROM
BEING ABLE TO DIVE INTO THESE
DAT AND ARGUE THAT THERE ARE
SPECIFIC REGIONS THAT WE SHOULD
FOCUS ON STIMULATING AT A
SPECIFIC LEVEL OF CURRENT, FOR A
SPECIFIC DIRECTION OF FLOW OF
CURRENT THROUGH THOSE BRAIN
REGIONS.
AND IN FACT, THAT'S THE PREMISE
BEHIND THE OVERALL APPROACH.
WE STARTED TO FOR YEARS AGO, OF
TAKING TDCS, TRAINING DATA BUT
THIS CAN BE ANY PARADIGM WE'RE
LOOKING AT BEHAVIOR CHANGE OR
TREATMENT RESPONSE WITH TDCS,
ACQUIRING T1 WEIGHTED MRIs,
FINDING ELEMENT MODELING,
TRAINING A CLASSIFIER, TAKING
THAT RESPONDER CLASSIFIER
SOLUTION AND THEN ULTIMATELY
FITTING IT INTO A NEW BRAIN, TO
THEN DETERMINE A PRECISION DOSE
OF SPECIFIC ELECTRODE LOCATIONS
AND SPECIFIC ELECTRODE INTENSITY
TO DELIVER TO TRY TO DELIVER THE
TREATMENT RESPONDER PROFILE OF
CURRENT INTO THIS NEW BRAIN WE
HAVEN'T SEEN BEFORE.
SO THIS OVERALL APPROACH LOOKS
SOMETHING LIKE THIS.
WE HAVE THESE MRIs FROM THESE
DATA SETS, WE FIT THE BRAIN WITH
AN FEM AND THEN IDENTIFY FROM
OUR PRIOR TRAINING DATA THESE
REGIONS OF SPECIFIC INTEREST
WHERE WE NEED TO DELIVER A
SPECIFIC AMOUNT OF CURRENT AND
THEN WE PERFORM A SINGLE GALSIAN
FITTING ACROSS THE BRAIN USING
EVERY POSSIBLE COMP BINNATION OF
CURRENT LOCATIONS AND INTENSITY
DELIVERED TO IDENTIFY THE
SPECIFIC MONTAGE AND INTENSITY
SO DOSE THAT BEST MATCHES THE
TREATMENT RESPONDER PROFILE.
ON THE RIGHT YOU CAN SEE A GROUP
LEVEL TREATMENT RESPONDER
PROFILE THAT WE THEN ATTEMPT TO
FIT INTO A NEW BRAIN.
WE ARE USING THE SINGLE GALSIAN
AND OTHER WORK IS USING
MULTIGALSIAN APPROACHES FOR
FITTING AND WE SPEEDING
PROCESSING TIME FELT.
IN THE EARLY DAYS IT WOULD TAKE
SICK WEEKS TO FIT A BRAIN, NOW
IT'S DOWN TO 6 MINUTES SO WE'VE
HAD IMPROVEMENT ON THAT FRONT
BECAUSE 6 WEEKS IS WAY TOO LONG
TO WAIT.
AT THE END OF THE DAY, THIS IS
CASE DAILY BASIS THEA WHERE WE
TOOK THE NONRESPONDERS FROM IT
AND ATTEMPTED TO REFIT THE DATA
TOI DENTIFY WHAT THE APPROPRIATE
DOSE FOR RESPONDER
CHARACTERISTICS AND THEN HERE
YOU CAN SEE THE 95% CONFIDENCE
LIMITS OF THE TREATMENT RESPONSE
PROFILE, THESE ARE THE
PRETREATMENT NONRESPONTDER, OR
THESE ARE THE NONRESPONDERS
BEFORE MODIFICATION TO THEIR
DOSE AND THIS IS MOW MODIFIED
DOSE.
NOW THIS IS STILL THEORETICAL,
WE HAVEN'T BROUGHT THESE BACK
AND STIMULATED THEM TO TRY TO
CHANGE THEIR BEHAVIOR, WE HAVE A
COUPLE OF PILOT TRIALS GETTING
OFF THE GROUND SO WE DEMONSTRATE
THIS DIRECTLY IN TERMS OF
POTENTIAL SUPERIOR EFFECTS FROM
PRECISION DOSING.
AT THIS POINT IT'S BEEN
PRIMARILY COMPUTATIONAL IN
NATURE, AND NOW WE'RE ATTEMPTING
TO DETERMINE WHETHER THIS IS
SPECIFICALLY GOING TO BE
EFFECTIVE.
IN ADDITION, THIS TECHNIQUE IS
DRIVEN BY THE NEEDS FOR LARGE
AMOUNTS OF DATA.
THE MORE DATA WE CAN HAVE ON
TREATMENT RESPONSE AND T1
WEIGHTED IMAGES TO TRAIN THESE
CLASSIFIERS, THE BETTER WE CAN
BE AT IDENTIFYING DOSE TO
ACCURATELY LEAD TO BETTER
PERFORMANCE AND WE RECENTLY
COMPLETED THE AUGMENTIVE
COGNITIVE TRAINING IN ADULTS, 3
IS A 379 PERSON TRIAL, IT SHOULD
BE RF1, THIS IS THE RO-1 THAT
FOUNDED THIS TRIAL AND WE ALSO
HAVE AN RF1 TO DO SECONDARY DATA
ANALYSIS AND CREATING
COMPUTATIONAL ANALYSIS ON 11
DIFFERENT INDIVIDUALS AND 11
DIFFERENT TYPES OF HIGH
DEFINITION MODELS AND THIS RF1
IS GEARED TOWARD DIVING AND
RUNNING AND ALL THESE METHODS TO
DERIVE DOSING BASED ON
CHAISKTISTICS OF RESPONSE AND
TREATMENTS IN THIS LARGE TRIAL
WHICH WAS RECENTLY COMPLETED.
IF THERE'S ANY OTHER TRIALS OF
THIS TYPE WHETHER IT'S
DEPRESSION, ANXIETY OR WHAT HAVE
YOU, AS LONG AS THERE ARE
TREATMENT AND OUTCOME DATA WE
CAN WORK CAN WITH IT, TO DERIVE
DOSING TO PUT BACK INTO THE
COMMUNITY TO TRIEF THIS FIELD
AWAY FROM ONE-SIZE-FITS-ALL TO
BRAIN SPECIFIC, PERSON SPECIFIC
MODELS.
SO I WILL END THERE AND I WILL
NOTE WE HAVE STWO NIH FUNDED
POST DOC POSITIONS IN THE LAB AT
PRESENT AND A RESEARCH SCIENTIST
POSITION, THE RESEARCH SCIENTIST
POSITION WILL BE RESPONSIBLE FOR
MANAGEMENT OF TRIALS IN THE LAB.
WE HAVE 4 NIH TRIALS,
INDIVIDUALS WILL WORK WITH ME
AND DR. [INDISCERNIBLE] ON A
NUMBER OF INTERESTING THINGS.
IF YOU KNOW PEOPLE INTERESTED
SEND AN E-MAIL AND THANK YOU FOR
YOUR TIME AND THE VERY MANY
PEOPLE THAT MADE THESE STUDIES
POSSIBLE AND ESPECIALLY OUR
FUNDING AGENCY, THE NATIONAL
INSTITUTE ON AGING.
[ APPLAUSE ]
>>THANK YOU VERY MUCH.
WE HAVE TIME FOR PROBABLY 2-3
QUESTIONS.
>> THANK YOU FOR A GREAT TALK
AND GREAT WAY TO START THE DAY.
WITH REGARD TO MACHINE LEARNING
PORTION, I WAS CURIOUS WHAT YOUR
NOTION OR MAYBE YOU HAVE DATA ON
ITS EFFICACY WITH REGARD TO MORE
VARIABLE BRAINS AND I HAVE IN
MIND STROKE BRAIN, I CAN SEE
WHERE THIS WOULD BE BETTER OR
WORSE, SO I WOULD LIKE TO HEAR
WHAT YOU THINK ABOUT THAT?
>>GREAT QUESTION.
WE'RE--THE REALITY IS THE
MODELING APPROACH IS ONLY AS
GOOD AS THE DATA WE PUT IN.
STROKE HAS BEEN 1 OF THE MOST
COMPLEX APPROACHES FOR US AND
MOST DIFFICULT TO MODEL.
THERE'S GREAT PEOPLE OUT THERE
DOING WORK WHERE THEY'RE SHOWING
REALLY NICE, VERY ACCURATE
MODELS WITH STROKE.
IN THIS CASE, IF WE CAN DERIVE
THE ELEMENT MODEL THAT'S
RELATIVELY ACCURATE TO GEF US,
YOU KNOW PERSON BY PERSON DATA
WE CAN APPLY THESE SAME
TECHNIQUES BUT AS YOU'RE
SUGGESTING, THE MORE NOISE
YOU'RE CREATE IN THE SYSTEM, THE
LESS EFFICACIOUS IT VERY LIKELY
WILL BE, HOWEVER WE'VE BEEN
WORKING SEPARATELY BOTH WITH
VIDEO AND TEAMS WITH A DIFFERENT
DIFFERENT LABS AT UF TO IMPROVE
AND CREATE SOME VERY AUTOMATED
APPROACHES FOR SEGMENTATION
ACROSS HIGHLY VARIABLE BRAINS.
NONAPOPTOTIC YOU WE'RE STARTING
WITH THE SIMPLE 1S LIKE, YOU
KNOW ACROSS THE LIFE SPAN OR
WITH ALZHEIMER'S DISEASE WHERE
YOU HAVE HYPER ATROPHY OR
HIPPOCAMPUS SCLEROSIS, IN
VARIOUS OTHER CHANGES AND
REGIONS AND TRYING TO CREATE AN
APPROACH THAT WILL ALLOW US TO
OWG MENTORSHIP SKILL AND MODEL
THAT DATA WITH VERY LITTLE INN
PUT BUT ALSO DIRECTLY GENERATE
FROM THE RAW DATA THESE JMAPS OR
ELECTRIC FIELD MAPS BUT GET THAT
IN SOMETHING COMPLEX AS STROKE
WILL TAKE QUITE A BIT OF WORK.
SO, YEAH, GREAT QUESTION.
>>THANKS VERY INTERESTING TALK.
I AM WONDERING, SO THERE'S A BIG
DISCUSSION IN MACHINE LEARNING
AND IF YOU GO APPROXIMATE THERE
FROM HIGH DIMENSIONAL DATA YOU
PREDICT A SINGLE OUTPUT.
LOOKING AT THESE PARAMETER MAPS
OR FEATURE MAPS IS NOT SIMPLE.
THERE MIGHT BE CORRELATION TO
INPUT DATA AND CERTAIN AREAS
LIGHT UP JUST BECAUSE OF THOSE
CORRELATIONS.
SO I'M WONDERING, YOU DIDN'T
SHOW THE DATA WHEN YOU BRING THE
PEOPLE BACK IN WITH THE MONTAGES
BUT IF YOU LOOK AT THOSE FEATURE
MAPS YOU DO YOU SEE AREAS THAT
LIGHT UP THAT MAKE SENSE YORE,
YOU KNOW THEY REQUIRE SORT OF
PATCHY THESE [INDISCERNIBLE]
YOU'RE SHOWING?
>>YEAH, WE SAW THAT MAP, I WAS
LIKE OH GREAT, THIS LOOKS LIKE
NOISE AND SO THEN WE LOOKED
INSIDE OF THAT AND I THINK PART
OF THE PROBLEM WE HAVE IS IT WAS
A SMALL DATA SET OF THE ALSO
WE'RE TRYING TO MOVE COGNITION
IN THESE DATA SETS WHICH IS
HYPER DISTRIBUTED AND PROBABLY
THE HARDEST TEST CASE WE COULD
POSSIBLY HAVE PICKED.
IN CONTRAST, WE'VE BEEN WORKING
WITH ANDRE OUT OF SAO P A OLO,
AND WORKING WITH HIS UNIVERSITY
AND DATA WITH DEPRESSION SO
CLINICALLY DEPRESSED PATIENTS
AND IN CONTRAST WE USED A SMALL
SAMPLE OF HIS DATA WITH T1S AND
THIS APPROACH AND IT ALMOST
LOOKS LIKE AN FMRI OUTPUT WHAT
WE'RE FIND FREE RADICALS
GENERATED HIS DATA AND MAPPED ON
TO DEPRESSION REALLY, REALLY
WELL.
IN THIS WE SHOULD PICK A TEST
CASE VERSUS COGNITION, BUT I'M A
COGNITIVE AGING GUY.
SO YOU'RE EXACTLY RIGHT.
WHAT WE'RE SEEING AS WE ADVANCE
AND GET MORE DATA FROM TRIALS,
WE ARE STARTING TO SEE THESE
PATTERNS THAT LOOK MORE LIKE THE
IMAGING PATTERNS WE WOULD EXPECT
AND I SHOULD PROBABLY PICK
SOMETHING OTHER THAN COGNITION
TO STUDY ON THIS.
>>I AM LOOKING FORWARD TO THE
DATA WHEN YOU BRING IT BACK.
>>YEAH, THANKS.
>>HEY, ADAM, GREAT WORK.
YOUR COGNITIVE TRAINING IS BEING
DONE SIMULTANEOUS WITH THE
APPLICATION FOR TDCS, IS THAT
CORRECT?
>>THAT IS CORRECT, THE FIRST
TWEBT MENCHUTES OF TRAINING, THE
FESTER 20 MACHINEUTES THEY
RECEIVE STIMULATION AND THEN
THEY CONTINUE DOING TRAINING
AFTER 20 MINUTES OF STIMULATION.
>>GREAT.
SO MY QUESTION IS YOU BUFULLY
DESCRIBED HOW 1 MIGHT GO ABOUT
INDIVIDUALIZING THE DOSE OF PART
OF YOUR INTERVENTION WHICH IS
THE TDCS, HOW DO YOU GO
INDIVIDUALIZING OR QUANTIFYING
THE DOSE OF THE COGNITIVE PART
AND HOW THEY--HOW THE 2
INTERACT?
>>YEAH, ABSOLUTELY BECAUSE
AGAIN IN THE COGNITIVE TRAINING
APPROACH WE HAVE A FIXED DOSE OF
3 MONTHS OF TRAINING AT 40 MINS
A DAY FOR 5 DAYS A WEEK EMPLOY
BUT YOUR QUESTION IS GREAT
BECAUSE IT WE CAN GO BACK AND
USE THE VARIABILITY OF THE DATA
OF WHAT THEY DID RELATIVE TO
THEIR RESPONSE TO BASE LINE
CHARACTERISTICS RUN THESE SAME
TYPE MODELS TO PREDICT TREATMENT
RESPONSE AND THE APPROPRIATE
DOSING OF TRAINING AND AS THESE
LARGER AND LARGER TRIEMS ARE
COMPLETED.
IN FACT, THERE'S AN ONCATEGORY
7600 PERSON TRIAL CALLED THE PAC
TRIAL WHICH WE'RE A PART OF IN
OLDER ADULTS THAT WOULD BE
DELIVERING DOSING OF ABOUT THE
SEAM 3 MONTHS IN VERY SIMILAR
COGNITIVE TRAINING APPROACHES
THAT UPON WE USED AND THAT SIZE
OF DATA WE COULD DO SOME COOL
ANALYSIS REGUARDING TREATMENT
RESPONSE AND CUSTOMIZING THAT
DOSE.
AT THIS POINT WE HAVE NOT TRIED
TO CUSTOMIZE OR SPECIFICALLY
DOSE THE COGNITIVE TRAINING SIDE
BUT YOU'RE RIGHT.
THAT'S A CERTAIN COMPONENT WE
ALSO HAVE TO CONTROL VERSUS SOME
OF THESE APPROACHES WHERE TDCS
IS THE PRIMARY INTERVENTION LIKE
IN DEPRESSION FOR EXAMPLE, OR IN
CHRONIC PAIN, WHERE WE WOULD
ONLY NEED TO DOSE THAT
COMPONENT.
YEAH, IT'S A GREAT QUESTION.
>>THANK YOU.
IF THERE IS NO OTHER QUESTION,
WE WILL MOVE ON TO THE IN
ACCIDENT SPEAKER, WHICH IS
DR. --[ APPLAUSE ]
--DR. SILVE NA, HOROVE TZ, FROM
THE NATIONAL INNSITUTE OF
NEUROLOGICAL DISORDERS AND
STROKE.
>>HI, GOOD MORNING EVERYBODY.
IT'S GREAT TO BE AT HOME IN A
MEETING IN PERSON.
SO THANK YOU FOR INVITING ME AND
LET ME TALK A LITTLE BIT ABOUT
OUR WORK ON TMS AND FMRI IN
MOVEMENT DISORDERS.
I DON'T HAVE ANY CONFLICTS TO
DECLARE, SO WHAT I WILL PRESENT
TODAY IS WHY WE THINK IT'S
IMPORTANT TO COMBINE TMS AND
FMRI IN MOVEMENT DISORDERS AND
THEN GO THROUGH A FEW WAYS TO
COMBINE THAT SOME SOME HAVE BEEN
MENTIONED ON OTHER TALKS BUT NOT
APPLIED TO MOVEMENT DISORDERS
AND I WILL TRY TO GO IN MORE
DETAILS.
SO YEAH, HOW WE CAN COMBINE THE
FMRI AND THE MEDS AND HOW THEY
CAN INFORM EACH OTHER.
SO WE MOVE, RIGHT?
WE TALK AND WE MOVE PARTS OF THE
BODY, ANY FUNCTION THAT WE DO,
WILL MOVE SOMETHING.
SO UNDERSTANDING HOW WE CONTROL
THE MOVEMENTS AND WHAT IS
EFFECTIVE IN THE DISEASE IS
IMPORTANT AND WE CAN--THE WAY
THAT WE THINK ABOUT THE
MOVEMENTS IS THROUGH THE
MOVEMENT, WE THINK ABOUT THE
SYSTEM, DIFFERENT PARTS OF THE
BRAIN THAT INTERACT THAT WILL
PRODUCE THE MOTOR OUTPUT THAT
WILL GO TO THE PERIPHERY.
SORRY, I'M HAVING ISSUES WITH
THE ADVANCE OF THE SLIDES.
>>OKAY, SO, SOME OF THESE
DISEASES WERE MENTIONED IN THE
[INDISCERNIBLE], PARKINSON'S
DISEASE, DYSTONIA, SOCIAL TREMOR
AND ALL THESE DISORDERS, AND YOU
HAVE SOMETHING IN THE BASAL
GANGLIA, SOME DEEP STRUCTURES
AND SOME CORTICALE AREAS BUT WE
KNOW THAT THEIR ARE SYSTEMS THAT
INTERACT AND SO THAT'S WHAT WE
WANT TO STUDY.
HOW THIS DISORDER PRESENT, HOW
WE CAN SEE THEM WITH FMRI AND
WHAT PART OF THE CIRCUITS ARE
AFFECTED OR HOW WE CAN ALTER
THEM.
SO WHAT WE GAIN FROM COMBINING
THE FMRI AND THE TMS, IS THAT WE
KNOW THAT FMRI ALLOWS FOR
OBSERVATION OF NETWORKS UNDER
INTERNATIONS, THAT'S SOMETHING
THAT HAVE BEEN A GROWN FIELD IN
THE LAST 15 YEARS OR SO.
AND WITH TMS, WE HAVE THE CHANCE
TO PERTURB THESE NETWORKS AND
THEN OBSERVE CONSEQUENCES IN THE
SHORT OR LONG-TERM AND THAT'S
ALLOWED US TO REALLY STUDY
WHAT'S GOING ON IN THE DIFFERENT
PARTS OR AT LEAST THE PARTS THAT
CAN ACCESS IN THE SYSTEM DOWN
STREAM.
SO THE FIRST TECHNOLOGY TRANSFER
I WANT TO MENTION IS SIMILAR TO
THINGS THAT HAVE BEEN PRESENTED
IN WAYS THAT WE CAN PROVE WHAT
IS OUR SIMULATION IS DOG.
SO WE USE FMRI TO OBSERVE, WHAT
IS THE MECHANISM BEHIND THE
STIMULATION, AND THIS IS THE
STUDY THAT WAS [INDISCERNIBLE]
AND CENSOR, IN THE GROUP THAT WE
WORKED TOGETHER ON AND IN THE
STUDY WE HAVE A SEQUENCE WHERE
THE SUBJECT NEEDS TO MEMORIZE A
TASK.
BEFORE THAT DID WE DID A BASE
LINE FMRI FOR RESTING STATE ASK
THEN WE CAN DO OTHER FMRI
RESTING ESTATE AFTER THEY LEARN
THESE SEQUENCES AND THEN WE
APPLY TMS INTERFERENCE OR
[INDISCERNIBLE] AND SUBJECTS GO
TO SLEEP AT THEIR HOUSE AND COME
BACK, AND THEN WE DO
PRERETESTING AND ANOTHER RETEST
TRIAL AND ALSO TEST FMRI.
SO WHAT WE FIND IS OF COURSE IN
BEHAVIOR THAT APPLY THE TMS
DURING REACTIVATION, REDOUSES
THE LEARNING THAT THEY HAVE, IF
YOU LOOK HERE, THE CONTROL IN
THE SESSION THAT WILL BE HERE,
THERE IS A BIG IMPROVEMENT IN
THE PERFORMANCE THAT IS NOT SEEN
WHEN AT THE TIME OF
REACTIVATION, THE CONSIDERATION
TIME THE SUBJECT IS QUESTIONED.
THE QUESTION IS WHY DID THIS
HAPPEN, THAT IS WE CAN EXPLORE
WITH THE FMRI, AND SO WE USE A
SEED IN THE MODEL CORTEX AND CAN
LOOK AT HOW THE CONNECTIVITY
GOES IN THE DIFFERENT CASES AND
THE DIFFERENT CONDITIONS AND
WAWE SEE IS THAT WHILE SUBJECTS
IN THE PREAND POST TESTING
BEFORE ANY INTERVENTION IN BOTH
GROUP HAVE INTERCONNECTIVITYS
BETWEEN THE MOTOR AREA AND THE
BASAL GANGLIA, ONCE WE APPLY THE
DIFFERENCE AND WE TEST THEM
AFTER CONSOLIDATION TIME IN THE
SLEEP, THERE IS A DIFFERENCE
WHERE THE GROUP IS NOT AFFECTED
GETS AN IMPROVEMENT WHILE THE
GROUP AFFECTED DOESN'T.
SO WHAT FMRI ALLOW US HERE IS
UNDERSTANDING WHAT IS BEHIND THE
EFFECT THAT WE HAVE IN THE
SIMULATION AND WE CAN SEE THAT
THE MODIFICATION OF THE MEMORY
CORRELATES WITH THESE CHANGES IN
CORRELATION, SO IT'S A GOOD
EXAMPLE OF HOW WE CAN LOOK AT
THE 2 BRAINS.
SO THIS IS CONTROLS OF SIMILAR
THINGS COULD BE APPLIED IN
PATIENTS OF COURSE.
ANOTHER STUDY NOW IN PATIENTS,
WE TRIED TO SEE, TO UNDERSTAND
WHAT IS THE ROLE OF THE
[INDISCERNIBLE] FOR DYSTONIA,
FOCAL HAND DYSTONIA WAS THE
TOPIC OF A HAND YESTERDAY SO
THOSE THAT WERE ALREADY HEARD
IS--DISEASE WHERE THE PATIENTS
HAVE A PROBLEM IN A FINE
CONTROL, VERY SPECIFIC FOR
EXAMPLE, A PERSON COULD HAVE A
DEFICIT IN WRITING THAT'S MORE
COMMON, WRITER CRAMPS AND SO
ONLY HAVE THESE CO CONTRAKSZ IN
THE FINGERS AT THE TIME OF
WRITING BUT NOT THAT MATCH ANY
OTHER ACTIVITIES.
SO THE CONTROL NETWORK THAT WE
CALL FOR THESE, WE KNOW IT
INVOLVES THE DARSAL AND VENTRAL
MOTOR OF THE DORSAL AND INTORIOR
INFERIOR PARRY ET AL LOBULE.
SO THE LOBULE WILL BE THE 1S
AFFECTED SO WE TRIED TO SEE
WHETHER WE CAN INTERVENE WITH
TMS, SIMULATED DIFFERENT AREAS
AND UNDERSTAND WHAT'S HAPPENING
IN THESE CONNECTIONS IN THE
PATIENT'S DIFFERENT THAN THE
CONTROLS.
OF COURSE, WE KNOW AND PROBABLY
ARE FAMILIAR WITH THAT DEPENDING
ON WHERE YOU STIMULATE, IT COULD
BE DIFFERENT RESULTS.
IT WAS A NICE DEMONSTRATION IN A
STUDY BY VERY CLOSE OF THE
PARIETAL CORTEX PRODUCE VERY,
VERY DIFFERENT RESULTS, SO WE
KNOW ALREADY THAT IT IS VERY
IMPORTANT AND THIS IS JUST ON A
STRUCTURAL T1 SO FOR US IT WAS
VERY IMPORTANT TO BE ABLE TO
DISTINGUISH THIS SURFACE, THE
DORSAL OF THE VENTRAL PATHWAYS
IN THE PREMOTOR AND THE PARIETAL
CORTEX, SO FOR THAT WE CHOOSE TO
USE FMRI AND I KNOW THIS IS A
CROWDED SLIDE BUT I MAINLY, THIS
IS THE IDEA THAT WE USE FIRST
IMANNUALING PARADIGM THAT
INCLUDE OTHER THINGS, FOR THIS,
BUT WE HAVE RESTING STATE THAT
WILL ALLOW US TO STUDY
CONNECTIVITY FOR THE FMRI TASK
THAT WILL ALLOW US TO IDENTIFY
THE DIFFERENT REEJIOKNOWS
RELEVANT FOR PERFORMING THE
TASK, THE FINE CONTROL TASK AND
THEN WE CAN USE THIS INFORMATION
FOR THE STUDY, WE SEE WHAT WILL
HAPPEN AND WE COULD COMPARE WITH
THE TMS RESULTS WITH THE GROUP
LEVEL, BUT ALSO WE CAN USE THIS
TASK TO LIMITED PARTNERSHIP
ABOUT THE SPECIFIC AREA FOR EACH
INDIVIDUAL ON HOW TO APPLY THE
SIMULATION, SO IF YOU'RE
GOINGANNA TOMICALLY, THIS WILL
BE THE SEEDS LIKE THESE LITTLE
DOTS LIKE WE WOULD PUT THE TMS
PROCEED.
HOIR WE CAN LEARN MORE AND FOR
THE SPECIFIC SUGJECT, THE WAY WE
DID WAS TO FIND ANATOMICAL
REGIONS THAT THEN LOOK FOR THE
VOXEL IN EACH SUBJECT THAT HAD
THE HIGHERACIVATION TO SEE THE
INTEREST AS YOU CAN SEE HERE
THERE ARE SLIGHTLY DIFFERENT
THAT ARE FINE BUT THE OTHER
REGIONS YOU MAY NOT HAVE THE
PEAK AT THE SAME PLACE THAT YOU
WILL BE IN ANATOMY AND WE WILL
GET BECOME TO THAT IN OTHER
STUDIESAs WELL.
SO THEN WE CAN USE NAVIGATION
BUT PUT THE COIL IN THE RIGHT
LOCATION BASED ON THE ACTUAL
ACTIVATION FOR THAT TASK FOR
THAT PEASHT THAT WILL PROBABLY
YIELD THE MORE EFFECTS FOR
AFFECTING THAT PARTICULAR TASK
SO WHAT WE OBSERVE HERE IS THAT
THE PMB TO 1 IS NOT THE REGION
AFFECTED AND THE IMBALANCE WAS
IN THE PARIETAL REGIONS.
SO 1 OF THE THINGS THAT 1 OF THE
CONCEPTS THAT THROUGH MANY TMS
STUDIES COME REGULARLY IS THE
IDEA OF LACK OF SURROUNDING
[INDISCERNIBLE] IN THE PATIENTS.
THERE IS NO SIGNAL GOING TO
BLOCK THE CENTER OF THE FINGER
YOU WANT TO USE AND THEN PRESS
OUT TO THE NEIGHBOR FINGERS
THAT'S WORK IN TMS DONE BY ABOUT
THE CONDITIONING AND SO WE WENT
OVER OTHER THINGS I WANT TO SHOW
IS WE CAN SOMETIMES LEARN
SOMETHING ON TMS AND THEN GO TO
A VERY DIFFERENT TECHNIQUE AND
TRY TO MOVE FORWARD, RIGHT?
SO THESE THAT I'M SHOWING HERE
IS COMPLIMENTARY INFORMATION TO
THAT, BUT THIS IS VASO FMRI AT 7
TESLA, WE DON'T HAVE A
SIMULATION HERE BUT WHAT WE CAN
DO IS NOW AT A VERY HIGH
RESOLUTION AND FMRI TRY TO
UNDERSTAND WHAT IS HAPPENING IN
THE BRAIN OF THESE PATIENTS,
THIS IS DATA FROM PATIENTS BUT
WE CAN SEE INDEED THAT THIS IS
THE FIGURE REPRESENTATION FOR
THE HEALTHY ATMOSHPHERE OR MORE
HEALTHY ATMOSPHERE, WE KNOW
THERE IS SOME CROSS OVER IN
DYSTONIA, BUT WE CAN SAY THAT
THIS IS THE HAND THAT IS
PROPERLY DISTRIBUTED HOWEVER IN
THE PATIENT, IN THE AFFECTED
VARIANT, SO IT'S HERE WE DON'T
HAVE THE CLEAN REPRESENTATION OF
THE FINGER WHICH SUPPORTS THE
WHYED THAT WE'RE NOT INHIBITING
OR SEPARATING THE ACTIVATION.
AND WHEN WE LOOK AT THE LAYERS,
WE CAN SEE THAT THEY'RE AFFECTED
HERE SHOWN IN GROWN AND THEY'RE
AFFECTED IN PLURIBU, THERE IS A
BIG DIFFERENCE INTO THE
INCREASING THE PATIENTS IN THE
SUPERFICIAL LEVELS WHILE
DECREASED ACTIVITY IN THE DEEPER
LAYERS IN THE BRAIN THAT COULD
BE WHAT IS INDEED CAUSING OR
THIS LACK OF INHIBITION AROUND
AND WE SEE THESE DIFFERENCES IN
THE VASOSIGNAL BUT ALSO IN THE
[INDISCERNIBLE] FMRI, SO MOVING
TO ANOTHER STUDY.
WE MENTIONED THAT IN THE
PREVIOUS STUDY IS THAT I SHOWED
THAT WE CAN USE THE TMS TO
LOCALIZE,--I MEAN THE FMRI TO
LOCALIZE THE STIMULATION IN
PLACE BY DOING ACTEST.
BUT SOMETIMES THE DESIRED TARGET
IS NOT CORTICALE AND WE KNOW
THAT TMS CAN ONLY BE APPLIED TO
THE CERTAIN DEPTH OF MANY OF YOU
ARE EXPERTS ON THAT OF THE
MODELING THAT I'M GETTING INTO
BUT WE KNOW WE CAN'T GET IT SO 1
OF THE WAYS THAT WE CAN GO IS BY
USING INFORMATION FROM FMRI, AND
CONNECTIVITY.
SO MAINLY IN THIS CASE, WHAT WE
DID IS USING RESTING STATE OF
FMRI FOR EACH INDIVIDUAL
SUBJECT, AND STRUCTURAL DATA
WHERE WE HAD DEFINED ARK MIG
DUALA DUALA REGION, EXTRACTED
TIMES FROM THE AMYGDALA AND THEN
LOOK AT THE FUNCTIONAL
CONNECTIVITY AND THEN IF WE HAVE
A TARGET AREA IN OUR CASE, THE
DORSAL LATERAL PREFRONTAL CORTEX
AND WE CAN FIND WHICH AREA
WITHIN THE DORSAL LATERAL WE
PREFER THE CORTEX AND WE KNOW
IT'S A PRETTY LARGENNA TOMICAL
REGION IS THE 1 THAT CORRELATES
MORE WITH THE AMYGDALA AND WILL
GOVERN US A BETTER CHANCE TO
MODIFY THE AMYGDALA ACTIVATION.
AND AS WE SEE HERE, THIS IS A
PILOT STUDY, THIS IS DIFFERENT
SECTIONS AND I WILL SHOW YOU THE
PARADIGM IN THE NEXT SLIDE BUT
WHAT I WANT TO POINT HERE IS
THAT WHILE MOST SUBJECT HAVE A
VERY CLOSE HIGHER CONNECTIVITY
POINT, IT'S NOT EXACTLY THE SAME
ON EVERYBODY.
AND THEN, OF COURSE 1 IS LOOKING
AT THE SUBJECT AND YOU CAN SEE
WHETHER THESE ARE THE SAME
RESULTS OR NOT BUT MAINLY EVEN
WITH THESE LITTLE GROUP FOR DOGS
THAT ARE VERY CLOSE TOGETHER,
THEY ARE NOT EXACTLY IN THE SAME
POINT.
SO THE PROGRAM WE HAVE AND THIS
WAS PROOF OF CONCEPT TREATMENT
IS, WELL, WE FIRST DO THE
RESTING STATE, FMRI, TO FIND OUR
TARGET REGION AND THEN WE CAN GO
THROUGH THE STIMULATION THAT WE
DO INTERMITTENT STIMULATION AND
WE CAN DO IN THIS TASK, WHEN WE
ARE LOOKING THE AMYGDALA HAS
HYPER-ACTIVITY IN THE PATIENTS
SO WE WANT TO SEE RESPONSES TO
FACES AND HAPPY AND POSITIVE AND
NEGATIVE BALANCE AND THEN WE CAN
SEE WHAT HAPPENED AFTER THESE
SERIES OF STIMULATIONS THAT WERE
DONE WITH CONSECUTIVE BASE AND
WE DO NOT DO TMS IN THE SCANNER
THAT'S TECHNOLOGICALLY MORE
DEMANDING AND SOMETIMES WITH
PATIENTS THAT MOVE AND BECOME
VERY TRICKY, RIGHT WHEN TRYING
TO BE VERY PRECISE IN THE
STIMULATION AND THEN THE SUBJECT
WILL MOVE IN THE SCANNER IS
SOMETHING THAT REQUIRES ANOTHER
LAYER OF CARE.
SO ANYWAYS, THIS IS DONE VERY
TIMELY WHERE WE HAVE THE
BEHAVIORIAL TASK, WE APPLY TMS,
WE GO RIGHT TO THE SCANNER, THEN
WE DO ANOTHER ITERATION AND WE
DO THAT A FEW TIMES.
AND WE DO OBSERVE THAT INDEED
THROUGH THE DIFFERENT VISITS,
OVER ALL CONNECTIVITY BETWEEN
THE AMYGDALA AND THE DORSAL
PREFRONTAL CORTEX TARGET, CHANGE
THE CASE OVER TIME BUT ALSO WE
SEE THAT THE BEHAVIOR CHANGE SO
NEGATIVE BALANCE DECREASE AND
THE POSITIVE BALANCE INCREASE SO
IT HAS THE WANTED EEIVET ON THE
PATIENTS.
SO THESE ARE 1 OF THE
TREATMENTS.
WE NOW TO MOVE TO DO THAT STUDY
AS RUN THE MICE DOUBLE BLIND
PATHWAY GIVES SEEB O CONTROL
TRIAL, IT'S A SMALL TRIAL WE'RE
RUNNING HERE AT NINDS AND I ALSO
TRY TO FIND STUDIES FROM OTHER
GROUPS OF CLINICAL TRIALS, THERE
ARE A LOT MORE IN THE
PSYCHIATRIC THAT IN THE
NEUROLOGY, ESPECIALLY MOVEMENT
DISORDERS, THERE IS ANOTHER
STUDY BEING RUP NOW IN CANADA
DAILY BASIS AT TITANS AND
INTERESTINGLY, THESE 2 STUDIES
OF FUNCTIONAL MOVEMENT DISORDERS
HAVE DISORDERS, [INDISCERNIBLE]
ALSO WITH DISORDERS, RIGHT?
THERE ARE OTHER STUDIES FROM THE
LITERATURE THAT HAVE DONE TMS
AND LOOKING AT DEFECT IN
CONNECTIVITY IN PATIENTS WITH
DIFFERENT LEVELS OF EFFECT BUT
HOWEVER, 1 OF THE TECHNOLOGY
TRANSFERS I WANT TO POINT IS
LIKE FOR EXAMPLE THESE
CEREBELLAR TMS, THAT CHANGE
FUNCTIONAL CONNECTIVITY IN
CANNED WHAT, SOME STUDIES IN
TINITUS, AND STUDIES ON
PARKINSONS PATIENTS AND
DYSTONIA, ALL THESE STUDIES ARE
ABOUT 10 YEARINGS OLD AND DIDN'T
MOVE TO CLINIC SO A LOT OF THESE
ARE PROOF OF CONCEPT AND VERY
HARD TO GET ALL THESE THINGS
TOGETHER, IT'S HARD TO SCAN THE
PATIENTS, IT'S HARD TO HAVE THE
TMSOT PATIENTS AND IT IS EVEN
HARDER TO TRY TO DO EVERYTHING
WITHIN THE TIME THAT YOU CAN
MONITOR THAT THINGS ARE
CHANGING.
SO I THINK UNTIL WE KNOW FOR
EXAMPLE, IF YOU LIKE TMS, HOW
LONG THE TREATMENT WILL LAST IS
IMPORTANT TO TIME WHEN YOU ARE
COLLECTING YOUR FMRI IF YOU ARE
TRYING TO SEE WHETHER THERE IS
AN EFFECT OR WHAT IS THE
MECHANISM OF EFFECT OR THE TMS.
SO IN SUMMARY, WE'VE SEEN THAT
TMS AND FMRI ARE USED TOGETHER
TO GET AN IMPROVEMENT ON HOW WE
APPLY TMS AND WHAT WE LEARN
ABOUT TMS BY ADDING THE MRI
COMPONENT AND THEY CAN HELP US
UNDERSTAND MOVEMENT DISORDERS,
HOPEFULLY EVENTUALLY BECOME
TREATMENT FOR SOME OF THEM.
SO WHAT I HAVE SHOWN IS THAT
FMRI CAN BE USED TO PROBE TMS,
CAN HELP FIND THE LOCATIONS, NOT
ONLY BY POINTING TOWARDS THE
BEST SPOT CORTEX BUT ALSO
BECAUSE WE KNOW THAT THE BRAIN
FUNCTION AS NETWORKS AND
DEFINITELY MOVEMENT DISORDERS
YOU CAN HAVE THIS EFFECT BY
HAVING DIFFERENT NODES AFFECTED,
FOR EXAMPLE, THERE WAS SOME
TALKS YESTERDAY ABOUT DEEP BRAIN
STIMULATION AND YOU CAN HAVE THE
SAME EFFECT OF DISEASE MODIFYING
EFFECTS BY APPLYING STIMULATION
IN DIFFERENT PARTS OF THE BRAIN
WITH DEEP BRAIN STIMULATION THAT
WE HOPE THAT THE SAME COULD BE
HAPPENING BY AFFECTING THIS
NETWORKS, WITH TMS, SO,
CONNECTIVITY COULD BE THE GUIDE
TO OUR DOOR TO BE ABLE TO TMS IN
AFFECTING DEEP STRUCTURES AND OF
COURSE AGGREGATING INFORMATION
WOULD IMPROVE OUR KNOWLEDGE.
SO WITH THIS, I WOULD LIKE TO
ACKNOWLEDGE THE COLLABORATORS IN
PARTICULAR, [INDISCERNIBLE] WHO
LED MOST OF THESE TMS STUDIES
THAT I PRESENTED.
AND THE REST OF THE TEAM THAT I
WANT TO POINT OUT WERE HERE AT
THE NOOH H AND PARTICIPATE
INDEED THE STUDIES THAT I'VE
SHOWN YOU.
THANK YOU.
[ APPLAUSE ]
>>THANK YOU FOR THE GRAT TALK
AND NOW IF THERE'S A FEW
QUESTIONS WE HAVE TIME FOR QUESTIONS
>>IF YOU ARE RELYING ON
ADMISSION FROM THE CORTEX TO THE
AMYGDALA DO YOU THINK IT'S ALSO
IN THE LOCATION OF OF THE
CORTICALE STIMULATION WILL ALSO
GIVE YOU A VERY DIFFERENT RESULT
IN TERMS OF YOUR THERAPEUTIC
EFFECTIVENESS.
>>YES.
SO YOU NEED TO BE SURE THAT YOU
ARE STIMULATING AN AREA THAT
WILL BE RELATED TO YOUR TARGET
SO THERE ARE WAYS TO DO IT, IT
COULD BE STRUCTURAL OR
FUNCTIONAL.
SO 1 OPTION WOULD BE TO DO
DIFFUSION AND FIND OUT WHAT IS
THE ACTUAL PATHWAY SO MANY GET
IN THE WHITE MATTER STIMULATED
CLOSE WHITE MATTER AND GET THAT
AND THE OTHER IS LOOKING AT
FUNCTIONAL WHERE IT IS
STIMULATED IN ANOTHER PLACE IN
THE DORSAL POSITIONOLOGICAL
FRONTAL CORTEX IT MAY NOT GO TO
THE AMYGDALA RIGHT?
IT MAY GO TO OTHER REGIONS OF
THE DORSAL POSITION AT LATERAL
CORTEX CONNECTS WITH ITS HIGH
CONNECTIVITY THROUGH THE BRAIN.
SO IF YOU DON'T FOCUS ON THAT,
YOU MAY OR MAY NOT REACH THE
AMYGDALA.
>>VERY NICE DATA, INTERESTING
THE VASOLAMINA PROFILE YOU
SHOWED, SEEMS UNAFFECTED, THAT
HAVE NOT AS CLEAN SEPARATION
BETWEEN THE DEEP AND SUPERFICIAL
LAYERS COMPARED TO THE AFFECT TD
[INDISCERNIBLE], THE AFFECTED
[INDISCERNIBLE] WAS CLEANER
ACTUALLY.
>>YES.
SO THE NONAFFECTED PROFILE, THIS
IS ONLY DATA FROM 4 SUBJEKS THAT
WE COLLECTED HERE BEFORE THE
SCANNER WAS SWAPPED BUT THERE'S
A LOT OF DATA COLLECTED FROM THE
SAME SCANNER WITH SAME SEQUENCE
WITH HEALTHY VOLUNTEERS.
WHAT WE SEE IN THE NONAFFECT
SIDE WHAT YOU EXPECT.
YOU EXPECT A BUMP IN THE UPPER
LAYERS AND A LITTLE BUMP IN THE
LOWER, DEEPER LAYERS BUT THEY
SHOULD HAVE SIMILAR PATTERN,
RIGHT?
IN THE PATIENTS WE HAVE MORE OF
AN IMBALANCE OF AN INCREASE IN
THE SUPERFICIAL LAYERS AND THE
DECREASE, THAT'S WHY--I MEAN
THERE'S DIFFERENCES IN BOTH
SIDES.
THAT'S WHAT MAKES IT KIND OF
MORE LIKE MUCH DIFFERENT BECAUSE
1 IS DECREASED AND THE OTHER IS
DECREASED FROM THE MIDDLE THAT
ARE TIERS IN THE CONTRA LATERAL
ATMOSPHERE SEEN IN THE PATIENTS.
>>THANK YOU VERY MUCH.
NOW WE CAN MOVE TO THE NEXT
SPEAKER.
THANK YOU VERY MUCH.
[ APPLAUSE ]
OUR SPEAKER WILL BE DR. LI-MIN
CHEN TALKING ABOUT MRI GUIDED
FOCUS ULTRASOUND FROM VANDERBILT
UNIVERSITY.
>>THANK YOU FOR INVITINGITOUS
PARTICIPATE IN IF WORKSHOP AND
THANK YOU FOR THE OPPORTUNITY TO
SHARE OUR DATA, I WILL TALK
ABOUT MRI GUIDED FOCUS ON
ULTRASOUND STIMULATION, AND I
HAVE NO FINE ASH INTEREST TO
DECLARE AND FOR BY NOW, SO WE
PROBABLY HEARD A LOT ABOUT, YOU
KNOW THE ADVANTAGES OR THE
BENEFITS OF USING ULTRASOUND AS
A STIMULATION TOOL AND WE'RE
MOTIVATED TO COMBINE IMAGING MI
WITH NEURAL, WITH FOCUSED
ULTRASOUND SO WE HAVE BEEN
WORKING ON A FEW ASPECT.
AND 1 IS A REALTIME VERIFICATION
OF THE THE ULTRASOUND BEAM
LOCATION WITH MRI ARFI, SO AS
YOU PROBABLY HEARD THE
FUNCTIONAL IMAGING PROVIDE US A
TOOL TO REALLY MONITORING THE
ULTRASOUND MODULATION EFFECTS.
I KNOW WE GAIN MECHANISTIC
UNDERSTANDING OF THE NEURAL
MODULATION AND MOST IMPORTANTLY,
NOT JUST AT THE TARGETED BRAIN
REGION, AND ALSO OFFTARGET IN
THE ENTIRE NETWORKS, SO, I
PROBABLY WILL TOUCH ON
SEVERAL--FROM SEVERAL ASPECT,
WOKNOW IS WE WILL SHOW THE BRAIN
STAY DEPENDENT BY DIRECTIONAL
STIMULATION OF THE ULTRASOUND
AND WE LOOK AT THE FIRST DOSE
RESPONSE AND I WILL ALSO SHOW
YOU SOME OF THE EXAMPLES WE HAVE
BEEN STUDYING THAT'S THE SENSORY
INDEPENDENT NETWORK IN NONHUMAN
PRIMATE MODEL AND IN THE END, I
WILL SHOW YOU SOME OF OUR NEWER
DATA SUGGEST THE MODERATOR--THE
ULTRASOUND CAN ALTER THAT WILL
AMILLIOEC CONNECTING NETWORK AND
RESTING STATE NETWORK.
SO IN THE END I WILL ALSO TOUCH
ON 2 OF THE FACTORS, THAT ARE
RELEVANT TO ULTRASOUND
STIMULATION, 1 IS THE
TEMPERATURE CONFOUND SO WE
DEVELOP A NEW METHOD TO LOOK AT
TEMPERATURE MONITORING USING MRI
DATA AND IN THE END I WILL TOUCH
ON SOME OF OUR DATA TO MONITOR
THE SAFETY OF THE ULTRASOUND.
SO OUR OVERALL APPROACH IS USED
COMBINED IMAGING AT THE 7 T OR 3
T, I HAVE DATA FROM BOTH
SCANNERS IN A MA CABBING MONKEY.
AND WE ALSO COLLECT DATA WITH A
SINGLE TRANSDUCER ULTRA SOUND
AND 128 CHANNEL TRANSDUCER.
SO THIS IS OUR OVERALL DATA
STRATEGY.
SO WE HAVE 6 MONKEYS, BEFORE WE
DO ANY ULTRASOUND STIMULATION,
WE USUALLY REQUIRE AC1 IS HIGH
RESOLUTION, T1 WEIGHTED
STRUCTURE IMAGE THAT WILL ALLOW
US TO ALIGN FUNCTIONAL DATA TO
THE MA CABBING ATLAS AND WE ALSO
APPLY FUNCTIONAL DATA TO EITHER
TACTILE STIMULATION OF THE HAND
OR HEAT STIMULATION OF THE HAND
TO IDENTIFY BRAIN REGIONS THAT
WE CAN TARGET FOR ULTRASOUND
NEUROMODDULATION.
SO WHERE YOU DO FUNCTIONAL MRI
AS A LOCALIZER TO IDENTIFY THE
REGION AND ONCE WE HAVE THOSE
DATA, AND WE FIRST OF ALL
ACQUIRE T1 WEIGHTED.
THIS IS 1 SCAN, AND LASTS ABOUT
7 HOURS AND WE FIRST OF ALL
ACQUIRE T1 IMAGE AND SIMI
RESOLUTION IMAGE AND THEN
RESTING STATE FMRI AND THEN FOR
7 HOURS WE OOH QUIRE FUNCTIONAL
MRI DATA AND WE PRODUCE A
POSITIVE OR ACTIVE CONTROL BY
USING EITHER TACTILE STIMULATION
OR HEAT STIMULATION.
NOW AFTER THE SESSION, WE ALSO
APPLY A RESTING STATE MRI DATA
DP IN THE END WE WILL ACQUIRE
SAFETY MRI DATA.
AND HERE'S THE DETAILS OF THE
DATA.
SO, I WANT TO POINT OUT IS THE
ANIMALS UNDERLIGHT ANESTHESIA,
AND WE USE EITHER A SINGLE
SURFACE COIL AT THE 70 OR A PAIR
OF FLEX COIL AT THE 3 T FOR
IMAGING DATA OPTIMIZATION AND
EACH IMAGING RUN IS ABOUT 10
MINUTES AND OVER 300 VOLUME.
WE DO STANDARD MRI ANALYSIS.
SO FIRST OF ALL I WANT TO SHOW
YOU OUR EFFORT TO TRY TO
OPTIMIZE THE RF AND THE REDUCE
THE TIME AND OUR ARFI IS OPTICAL
TRACKING TBIEDED IS SIMILAR TO
NEURAL NAVIGATION AND THIS IS
THE WORK DONE BY [INDISCERNIBLE]
GROUP.
SO YOU CAN SEE THIS IS THE
MARKERS, AND WE--THIS IS THE
MONKEY STILL TEXT BEING FRAME,
THIS IS THE TRANSDUCER, AND WE
HAVE THIS MARKER WE CAN USE THAT
FOR OPTICAL TRACKING AND THIS IS
THE ILLUSTRATION.
SO WHEN WE HAVE THE MONKEY HERE,
AND YOU CAN SEE HERE, THIS IS
MONKEY BRAIN WITH THE MI DATA
AND THEN THIS OPTICAL SIMULATED
TRANSLATIONAL RESEARCH JUDGE
ECTOMYOSINRY OF THE ULTRASOUND
THEME.
I FORGOT TO MENTION 1 THING IS
BEFORE EACH ANIMAL ENTER
ULTRASOUND STIMULATION, WE WILL
ALSO REQUIRE SAFETY DATA AND SO
CHARLES' GROUP COMBINED THIS FOR
THE TRAJECTORY FOR THE
TARGETING.
SO THIS IS OPTICAL TRACKING
TRAJECTORY.
AND THIS IS JUST SHOWING YOU, WE
HAVE SUCCESSFULLY TARGETED, THIS
IS THE AREA, AND YOU CAN SEE
WHEN WE INCREASE THE PRESSURE
AND THEN THE TRANSDUCER
INTRODUCED THE DISPLACEMENT,
ALSO INCREASE, THIS IS A DOSE
RESPONSE TO SHOWING METHOD TO
DETECT THE PULSES EMPLOY AND
IMAGE, I SHOW YOU AND WHY
OPTICAL TRACK SUGGEST IMPORTANT
BECAUSE OPTICAL IMAGESERAL
TRACKING ALLOW US TO DO REDUCE
THE ARFI AND THAT CAN SAVE TIME
AND ALSO MINIMIZE THE ULTRASOUND
EXPOSURE AND WE HAVE RECENTLY
DEVELOPED A NEW METHOD, THIS IS
BY WILL GRIS ORDER OF MICRONS'
GROUP AND BY GRADUATE STUDENT
LAURA AND SHE DESEENED THIS
METHOD, CAN YOU DO REDUCED FIELD
OF VIEW ARFI AND FOR VERY HIGH
RESOLUTION IT'S ABOUT
2-MILLIMETER CUBIC SIZE BUT IN 2
MINUTES.
SOPHISTICATED THIS IS A VERY
FAST ARFI IMAGE AND HERE THE
IDEA IS WE ARE TRYING TO MEN
MYSELF ARFI EXPOSURE AND THE
PAPER JUST PUBLISHED IF YOU ARE
INTERESTED, YOU CAN TAKE A LOOK
AND THEN, WE WENT OUT, SO WHEN
WE KNOW ARFI BY WHEN WE USE ARFI
TO VERIFY THE TARGET IS AT OUR
INTENDED LOCATION AND THEN WE
WILL DO FUNCTIONAL MRI
EXPERIMENTS.
SO OUR FUNCTIONAL MRI EXPERIMENT
IS INTERLINKED EXPERIMENT
CONDITION, SO WHAT DO I MEAN BY
THAT?
SO WE USUALLY ALWAYS HAVE A
BUILDING FUNCTIONAL, LIKE
POSITIVE CONTROL.
SO IN THIS CASE WE HAVE A
TACTILE STIMMULES OF THE MONKEY
HAND AND THEN WE INTRODUCE
ULTRASOUND STIMULATION SO WE
HAVE AN INTERLEAVED SESSION, WE
HAVE A TACTILE, PLUS ULTRASOUND.
AND THE TRACKING THE TRAJECTORY,
AND THIS IS THE ARFI DATA SO
THEY ALIGNED PRETTY WELL AND SO
HERE BOTTOM SHOWING YOU, THIS IS
THE FUNCTIONAL MRI MAP,
INTRODUCED BY TACTILE
STIMULATION AND YOU CAN SEE THE
C, THIS IS THE C WITH FUNCTIONAL
ADENTIFIED SO WE WERE ABLE TO
OVERLAY THE ARFI, THE ULTRASOUND
BEAM AFTER THE TARGET VERIFIED
BOY ARFI.
AND AND SO WHAT WE SEE, WITH
THIS DATA, SO HERE YOU CAN SEE
THE TOP 1 WHEN WE DELIVERED A
TACTILE STIMULATION TO THE HAND,
WE SEE ACTIVATION IN THAT AREA
WE EXPECT.
FOR EXAMPLE, THE SENSORY SYSTEM,
THE MEDIAL PC C AREA IN THE
CORTEX AND WHEN WE DELIVER THE
FIRST STIMULATION AT THE C, THIS
IS AREA 3 A, 3 B, EQUIVALENT TO
THE MONKEY--I'M SORRY THE RODENT
PRIMARY SENSORY CORTEX.
AND YOU CAN SEE, WE SEE SIMILAR
ACTIVATION AND WHEN WE LOOK AT
THE TIME COURSE, YOU CAN SEE THE
FIRST IS THE BLUE TIME COURSE,
THE BACKGROUND IS THE STIMULUS
ON AND OFF BOX DESIGN AND USING
THE 2 KILOPACIFIC AT
STIMULATION, IT LOOKED QUITE
COMPARABLE BOTH SIGNAL CHANGE
WITHIN THE SENSORY SYSTEM IN THE
ON TARGET AND OFF TARGET REGION
AND HERE'S SHOWING YOU THE TIME
COURSE, CAN YOU SEE THE TIME
COURSE, THIS IS OUR TARGET,
OFFTARGET REGION, PRETTY ROBUST
SIGNAL CHANGE.
AND THEN WHAT WE DID NEXT IS WE
BASED ON THE SIMULATION AND THEN
WHEN WE LOWER THE THRESHOLD BUT
WHY LOWER INTENSITY TO THE
[INDISCERNIBLE].
SO THE SEE THE TACTILE
SIMULATION ALONE AND THIS IS THE
WHOLE NETWORK SLIDING UP AND
WHEN WE HAVE A MODERATING TEST
SOWBD AND YOU ALSO SEE
ACTIVATION, AND SBA IS THIS 1,
SO WHEN WE HAVE COMBINED THE
TACTILE WITH THE MODERN
INTENSITY ULTRASOUND AND YOU CAN
SEE THE AGHTIVATION PRETTY MUCH
SIGNIFICANTLY REDUCED AND WE
HAVE--I GENERATE CONTRAST MAP,
THE CONTRAST MAP IS THE 1
CONDITION SUBTRACT ANOTHER
CONDITION SO THE PLURIBU VOXELS
BASICALLY TELLS YOU WHERE WHICH
REGIONS HAVE BEEN SUPPRESSED AND
TO SUPPORT THIS SO THIS IS TIME
FOR ANALYSIS, YOU CAN SEE HERE,
THE BLUE IS COMBINED TACTILE
WITH MODERATE ULTRASOUND IS
PRETTY MUCH SUPPRESSED NOT ONLY
AT THE TARGET BUT ALSO THE OFF
TARGET RENALLION.
WE HAVE A CONTROL ROI, THIS IS
THE WHITE MATTER YOU DON'T SEE
THAT MUCH SIGNAL CHANGE.
SO AND THEN, WE--NOW WE HAVE 1
HIGH TEST, LOW IPT GREATER
TENSITY RANGE AND WE LOOK AT, WE
HAVE ACTIVATION WITH 2-5 AND WE
HAVE SUPPRESSION WITH THE 425
AND THEN WE SAY WHAT IS THE DOSE
RESPONSE?
CAN WE LEARN ANYTHING BY LOOKING
AT THE DOSE RESPONSE?
I WANT YOU TO LOOK AT OUR
DESIGN.
WE HAVE ULTRASOUND WITH 3
DIFFERENT DOSES AND THEN WE HAVE
A TACTILE ACTIVATION, TACTILE
CONTROL.
SO WHAT DO WE SEE HERE, I WANT
TO YOU LOOK AT THIS MAP.
OKAY, SO, HERE, THIS IS OUR
TARGET.
BASICALLY WHEN WE LOWER
INTENSITY OF THE ULTRASOUND BEAM
AND THEN AS YOU EXPECTED THE
PERCENTAGES BOTH SIGNAL CHANGE
IN DECREASES AS IT'S A LINEAR
DEKREEZING AND THIS IS THE
TARGET AND THIS IS THE WHOLE
TIME COURSE AND THEN, THIS OTHER
AREAS ARE INTERCONNECTED, BRAIN
REGIONS TO THIS AREA, 3 A AND 3
B MONKEYS.
AND WHAT'S INTERESTING IS THIS
1.
SO WHEN WE COMBINE THE FIRST
WITH TACTILE TOGETHER AND
COMPARE WITH TACTILE ALONE AND
THEN, YOU CAN SEE AT THE TARGET,
THE RESPONSE DIFFERED HERE.
HIGH INTENSITY IS NO EFFECT ON
THE TACTILE RESPONSE BUT THE
MODERATOR AS WE SHUOF THE SHOWED
YOU BUT WE HAVE SUPPRESSION, WE
LOWER INTENSITY TO 200
KILOPACIFICCAL INTENSITY AND WE
SEE EVEN LESS, LESS INHIBITION,
SO IT'S NOW SHOWING A
[INDISCERNIBLE].
SO HERE GIVE YOU A BETTER IDEA.
SO, THE LINE DOSE CONDITION, THE
3 DOSES, THEN THE GREEN LIGHT
THIS IS THE V-SHAPE AND WHEN WE
HAVE THE ULTRASOUND PLUS DACTILE
STIMULATION, SO THE WHYEDS WE'RE
TRYING TO USE ULTRASOUND TO
MODULATE THE TACTILE RESPONSE
AND SO YOU CAN SEE WHEN THE
BRAIN IS IN DIFFERENT STATE.
WHAT DO I MEAN BY STATE.
SO THE BRAIN IS NOT ENGEAJING
ANY TASK AND WHEN WE REDUCE THE
INTENSITY OF THE FIRST AND THE
BOLD SIGNAL DECREASES.
WHEN WE HAVE THE AREAS ACTIVATED
BY TACTILE STIMULATION, NOW THE
CONCURRENT DELIVERY NOW HAVE
INTRODUCED THE VERY BEST
RESPONSE FUNCTION.
IT'S A VSHAPE.
IT'S SIGNIFICANTLY REDUCED AT
THE MODERATE THE INTENSITY.
IF YOU LOOK AT OFFTARGET
REGIONS, HOW THEY ARE FOLLOWING
WHAT'S CHANGING AT THE TARGET SO
WE DID A VERY SIMPLE CORRELATION
ANALYSIS AND HERE YOU CAN SEE AT
THE RESTING STATE, THE TOP 1S
FIRST ALONE AND THEN THE
CORRELATION IS PRETTY AND THEN
OFFTARGET REGION.
IN OTHER WORDS RESTING STATE
OFFTARGET RATE FOLLOW WHAT
HAPPENED WITH THE TARGETED
STIMULATED AREA BUT INTERESTING
IS THIS FINDING SO WHEN WE HAVE
ULTRASOUND INTERACTING WITH THE
ACTIVATED BRAIN WHERE THE NEURON
IS WORKING HARD AND THEN WE SEE
DIFFERENCES BETWEEN CORTICALE
REGIONS AND THEN THE THALAMUS
REGION SO YOU SEE THERE'S
ACTUALLY NEGATIVE CORRELATION TO
THE VPL NUCLEI OF THE THALAMUS.
SO OUR DATA INDICATE ACTUALLY.
THE ULTRASOUND INTERACTING THE
CORTEX, THE INTERACTION SEEMS
VARIED BETWEEN CORTICALE,
CORTICALE CONNECTIONS VERSUS
CORTICALE THALAMIC CONNECTIONS
AND WEB CONNECTED HAVE A
HYPOTHESIS WE THINK IS PROBABLY
REAL RELATED TO THE FEET FORWARD
AND FEEDBACK CONNECTIONS SPRINTS
BETWEEN DIFFERENT AREA, THAT'S
OUR HYPOTHESIS.
AND THEN I WANT TO MOVE ON TO
INTRODUCE SO NOW WE HAVE THE
ARFI IN PLACE, SO WE WANT TO
EXTEND THE ABILITY FOR
APPLICATION IN MUSEUM MAN, IS IF
IN CASE THE ULTRASOUND BEAM IS
OFF TARGET LIPID, CAN WE USE
ELECTRICAL STEERING ABILITY AND
TRY TO MOVE IT BACK.
SO THIS IS WHAT WE TRIED WITH
THE 128 ELEMENTS OF FIRST ARRAY.
SO HERE I'M SHOWING YOU, WE CAN
USE ELECTRIC STEERING TO MOVE
THE TARGET FROM THE THALAMUS
TARGET TO THE INSULAR CORTEX AND
AND HAVE THIS DOWN RANGE ABOUT 2
SEBT METERS SO THAT COVERED A
PRETTY GOOD RANGE AND WHAT WE
CAN DO.
AND HERE WE HAVE 1 PROJECT
SUPPORTED BY HEAL INITIATIVE, SO
THE IDEA IS DEVELOP THIS MRI
GUIDED SYSTEM THAT WILL ALLOW US
TO INTRODUCE PAIN RELIEVE IN
CHRONIC PAIN PATIENTS.
AND CAN WE INTRODUCE ANY
SUPPRESSIVE EFFECT WITH
ULTRASOUND.
SO BASED ON THE DATA WE HAVE,
NOW WE DESIGN THIS EXPERIMENT TO
LOOK AT 3 DIFFERENT BRAIN
REGIONS HAS BEEN TARGETED IN DBS
STUDIES FOR PAIN RELIEF, SO
THESE ARE 3 AREAS WE DESIGN, 1
ISAN TERIOR SINGULAR CORTEX AND
THE OTHER IS WE LOOK AT THALAMUS
AND ALSO THE PARADACTYL GRAY.
SO THESE 3 AREAS ARE REP ARE
SENTATIVE IN TERMS OF THEIR
LOCATION IN THE BRAIN, IT'S
SUPERFICIAL IN THE DEEPER IN THE
BRAIN AND SO, HERE, WE'RE
SHOWING OUR ARFI DATA SO YOU CAN
SEE, WE CAN RELIABLY TARGET THIS
AREA WITH NO PROBLEM WITH THE
CHANNEL ARRAY.
SO I'M GOING TO SHOW YOU SOME OF
OUR FUNCTIONAL DATA FROM THE
THALAMUS STIMULATION.
SO AND HERE AGAIN, WE TRY TO USE
THE MODERATE PHOTON TO SUPPRESS
THE HEAT RESPONSE, THE IDEA IS
MAYBE IT CAN REDUCE PAIN.
SO THIS 1 IS WHEN WE STIMULATE
WITH HEAT WITH A TEMPERATURE
THAT CAN ELICIT BURNING
SENSATION IN HUMANS WE CAN LIGHT
UP THE ENTIRE NETWORK AND THIS
IS VERY CONSISTENT OR SIMILAR TO
WHAT WE REPORT IN A HUMAN
LITULATURE WHEN YOU GIVE THE
SAME STIMULUS TO THE HUMANS AND
THIS IS SHOWING ACTIVATIONOT
INFLATE OF THE BRAIN.
SO MEN WITH HIGHER WE HAVE THE
FIRST ADDED TO THE HEAT
STIMULATION, AT THE THALAMUS
NUCLEUS, AND SOME AREAS
INHIBITED, THIS IS THE LIST OF
AREA BEING SUPPRESSED BUT
INTERESTINGLY WE ALSO HAVE THE
AREA ACTUALLY GETTINGS
ADDITIONAL RESPONSE, WE CALL IT
EXCITED, SO, WE DON'T KNOW WHY
IS THIS CASE, SO THIS IS OUR
OBSERVATION.
SO HERE'S SHOWING YOU THE
CONCOURSE.
SO THE RED IS THE HEAT RESPONSE
AT EACH INDIVIDUAL ROI WAS
SELECTED FOR THIS ANALYSIS AND
THE BLUE CURVE IS THE HEAT
PLASMAS AND DELIVERED AT THE
THALAMUS, SO GENERALLY YOU CAN
SEE, WE SEE DRASTIC SIGNIFICANT
REDUCTION IN THE PERCENTAGE BOLT
SIGNAL CHANGE AT EACH FMRI, I DO
WANT TO TELL YOU WE DO SEE SOME
AREAS ACTUAL RESPONSE GET
ENHANCED BUT I'M NOT SHOWING THE
TIME COURSE HERE.
THE NEXT AS WE PROBABLY
APPRECIATE FOR CHRONIC PAIN
NETWORK SO IT'S PROBABLY A
CIRCUIT PROBLEM, 1 IDEA IS TO
UNDERSTAND ULTRASOUND MECHANISM,
WE WANT TO ELECTRIC AT WITH WE
SUPPRESS THE THALAMUS RESPONSE,
YOU KNOW WHETHER WHAT IT DOES TO
THE ENTIRE--SO THE ANALYSIS WE
COME UP TO LOOK AT IS WE CALLED
EFFECTIVE CONNECTIVITY ANALYSIS,
THE PSYCHOPHYSIOLOGICAL ACTION
ANALYSIS.
SO ANALYSIS ALLOW US TO LOOK AT
THE TASK OF SPECIFIC INTERACTION
TBEEN BRAIN REGIONS ARE INVOLVED
IN THE SAME TASK, SO HERE, WE
FOCUSED ON THALAMUS BECAUSE THIS
IS WHERE WE'RE PERTURBATING AND
HAD IS DURING THE HEAT
STIMULATION AND THEN WE
IDENTIFIED THIS AND WE EXTRACTED
THE BOLD SIGNAL AND WE USE THIS
SIGNAL AS A REPRESSOR TO FIND
WHERE IN THE BRAIN THOSE AREA
ACTUALLY--STRONGLY CONNECTED TO
THIS THALAMUS NUCLIER DOING THE
PAINFUL STIMULATION PROCESSING.
SO WE CALLED IT THE THALAMUS
EFFECTIVE CONNECTIVE FOAT WORK.
SO WHAT HAPPENS?
SO HERE IS THE THALAMUS PET
NETWORK SO THIS IS DIFFERENT
THAN WHAT WE HAVE JUST SEEN THE
NATURAL PAIN NETWORK THIS IS THE
SIDE VIEW AND CENTER VIEW AND
THIS IS ALL AREAS CONNECTED AND
PART OF THE PAIN NETWORK FOR
EXAMPLE, THE MOTOR CORTEX AND
THE SENSORY CORTEX AND WHEN WE
HAVE THE THALAMUS MODULATED BY
FIRST AND PROBABLY YOU CAN SEE
SOME OF THE AREAS HAVE MORE
CHANGES THAN OTHER AND FOR
EXAMPLE, THE POSTERIOR INSULAR
CORTEX RESPONSE IS NOW SHOWING
UP WHEN WE WHEN WE PERTURBATED
OUR RESPONSE.
AND SO, THAT'S THE MAP AND THEN
WE DID PAIR WISE, THE RI BASED
ANALYSIS, SO THIS IS THE METRIC
SHOWING YOU ALL THE RIs HAVE A
STRONG CONNECTION TO THE
THALAMUS NUCLEAR AND THEN IN 2
CONDITION, HERE LEFT METRICS,
THIS IS THE HEAT PLOT FIRST, THE
FIRST IS INTRODUCED TO SUPPRESS
THE THALAMUS RESPONSE AND
PROBABLY YOU CAN PROASHT AFTER
THE THALAMUS SUPPRESSION, THE
OVERALL CONNECTIVITY PATH AND
CHANGE.
AND ALSO SOME OF THE AREAS ARE
SIGNIFICANTLY SUPPRESSED.
SO THE STAR, YOU SEE HERE THAT
THOSE ARE SIGNIFICANTLY CHANGED
THE PAIRS.
AND THIS IS THE BETA CO
EFFICIENT IN BETWEEN THE
THALAMUS SEED AND THE ROI WE
CHOOSE TO PLOT HERE.
SO THE MESSAGE IS, WHEN WE
SUPPRESS THE THALAMUS HEAT
RESPONSE REGION, THE CONNECTION
BETWEEN OTHER AREAS FOR THE
CONNECTION SAMPLES ALSO MOST OF
THEM ARE SUPPRESSED.
AND WE ALSO PERFORMED THE
HIERARCHICAL CLUSTER ANALYSIS,
THE WHYED IS WHEN WE SUPPRESS
THE NUCLEAR PAIN RESPONSE, WHAT
HAPPENED TO THE NETWORK
OPTIMIZATION, AND WHAT WE FOUND
IS, THIS IS THE HEAT NETWORK,
THOSE ARE THE AREAS ARE INVOLVED
AND WHEN WE DO HIERARCHICAL
ANALYSIS, CAN YOU SEE SOME AREAS
ARE CLUSTERED TOGETHER AND MEANS
THEY'RE FUNCTIONALLY MORE
SYNCHRONIZED AND THEN WE SAY WE
HAVE A PLURIBU NETWORK AND HAVE
A RED SUBNETWORK.
WHEN WE HAVE THE ULTRASOUND
SUPPRESSED, THE THALAMUS PAIN
RESPONSE AND YOU CAN SEE, THE
ORGANIZATION CHANGE, SO, AFTER
THE EXPOSURE, THE NETWORK
REORGANIZED.
AND SO NOW WE LOOK AT WHEN
WE--WE INTERESTINGLY, WHEN WE
INTRODUCE THE SAME ULTRASOUND
THEME TO THE ACCAND 2 OF THE
PVG, WE SEE ALSO REPRESSIVE
EFFECT SO THAT'S THE AREA WE'RE
SHOWING SO THE PARAMETER SEEMS
TO BE WORKING IN OUR EFFORT TO
SUPPRESS HEAT INDUCED RESPONSE.
SO THE NEXT 1 I WANT TO SHOW
YOU, RESTING STATE IS ALSO
ANOTHER MEASUREMENTS MIGHT TELL
US ABOUT THE POST ULTRASOUND
EFFECT SO AS A THERAPY WE WANT
TO KNOW, WHAT--HOW LONG THE--YOU
KNOW THE PROTURBATION OR
MODULATION LASTS, SO THE 1 WAY
WE TRY TO ELECTRIC AT IT IS WE
ARE LOOKING AT THE RESTING STATE
NETWORK CHANGE BEFORE AND AFTER
ULTRASOUND EXPOSURE AND THIS IS
THE MAP AND SO THIS 1 IS THE
BEFORE ULTRASOUND EXPOSURE, SO
THIS IS THE--THIS IS THE NETWORK
DEFINED BY RESPONSE TO THE
ENHANCED STIMULATION, WE CALL IT
THE NETWORK.
AND AFTER THE ULTRASOUND
SUPPRESSED THALAMUS AND YOU CAN
SEE, IT'S MUCH COOLER IN A
TEMPERATURE, THAT MEANS OVERALL,
OVERALL THE CONNECTIVITY IS
DECREASED, THIS IS AFTER THE
ULTRASOUND EXPOSURE.
BUT SOME OF THE AREAS, YOU CAN
SEE, IT GETS ENHANCED.
AND THIS IS OUR PLOT, SO THE
BLUE, THAT'S THE HEAT ALONE, AND
THE RED, THIS IS HEAT, PLUS
ULTRASOUND PLUS SUPPRESSION, SO
YOU CAN SEE THE ORE ALL
CORRELATION, THE OVERALL
INTENSITY DECREASED BUT 1 VERY
INTERESTING FINDING IS--I'M
SORRY, SOMEHOW--OH, GO BACK?
SORRY.
I APOLOGIZE.
THIS 1 IS SOMEHOW, THIS--THIS 1
DIDN'T WORK AND WE HAVE ALSO
TRIED THE SAME NETWORK BUT WHEN
WE SUPPRESS THE PVG, AND THEN
PVG HAS A VERY DIFFERENT EFFECT,
I'M SORRY THE PVG ALSO INDUCED
SAME SUPPRESSION, SO IN WORTH
ORDERS IF WE SHUT DOWN THE
THALAMUS OR THE PVG ACCIDENT THE
RESTING STATE PAIN NETWORK IS
THE CONNECTIVITY STRENGTHS ARE
REDUCED.
AND.
>>YOU HAVE 2 MINUTES.
>>SO THE TEMPERATURE MONITORING
IS ANOTHER CONFOUND FOR AWLT
RASOUND STIMULATION SO IESM
SHOWING YOU THE 1 METHOD WE
DEVELOPED ACTUALLY WE'RE USING
WITHOUT APPLY ANYMORE DATA USING
FUNCTIONAL IMAGINGA TO MEASURE
THE PAPER.
SO THIS IS A NEW PAPER PUBLISHED
LAST MONTH AND IF YOU'RE
INTERESTED YOU CAN LOOK THE THIS
WORK BY [INDISCERNIBLE] AND HIS
STUDENTS AND WE'RE USING
FUNCTIONAL DATA TO MEASURE THE
TEMPERATURE AND I'M JUST SHOWING
YOU 1 DATA HERE AND THIS IS IN A
PUBLICATION IF YOU'RE
INTERESTED, WE HAVE A BETTER
CONTROLLED OPTICAL IMAGES O
GENETICS STUDY MODEL AND WE'RE
USING LASER TO DHAIMPLEG AND
STIMULATE AND HERE SHOWING YOU
WE CAN--WE CAN MEASURE THE
TEMPERATURE CHANGE AT THE PROBE,
AT THE TIP OF THE PROBE AND WITH
THE ACBEERACY OF .02-DEGREES.
SO IT'S VERY SENSITIVE TOGETHER.
I WOULD RECOMMEND IF YOU'RE
INTERESTED TO MONITOR, AND THEN
IN THE END, AS YOU SAY THE
SAFETY IS ALWAYS A CONCERN SO WE
ARE DEVELOPED THE PIPELINE TO
LOOK AT USING THE BEST IMAGING
TO MONITORING THE MI SAFETY, SO
HERE IS ALL THE METHOD AND JUST
SHOWING YOU SOME OF THE DATA WE
ACQUIRED AT THE END OF EACH
SESSION, TAKES ABOUT 30 MINUTES
AND WE--WE DO MAKE IT MORE
SENSITIVE AND HERE I GIVE AN
EXAMPLE, IF WE DO BBB OPENING WE
CAN DETECT THE SIGNAL AT THE
TARGETING SYSTEM THEET YEAH, SO
THIS IS JUST SUMMARIZE WHAT I
JUST DESCRIBED, YES, THANK YOU
SO MUCH AND THIS IS OUR--THIS IS
REALLY A MULTIDISCIPLINED TEAM
WORK AND 3 OF US AND OUR
COLLABORATOR, OUR DIRECTOR,
LEADER ISSUES EVERYONE IT'S
REALLY TEAM WORK ANDIME HONORED
TO BE PART OF IT.
THANK YOU VERY MUCH.
AND ALSO THANK YOU FOR THE
FUNDING.
[ APPLAUSE ]
>>WE CAN TAKE 1 OR 2 QUESTIONS.
>>BEAUTIFUL TALK, VERY ROBUST
EFFECTS.
SO YOU IMAGE UP TO 7 HOURS, DO
YOU HAVE A SENSE OF HOW LONG
THESE CHANGES IF FUNCTIONAL
CONNECTIVITY LAST?
HOW LONG WAS IT PERFORMED AFTER
THE ULTRASOUND?
>>YEAH, SO OUR MEASUREMENTS
BASICALLY TELL US LIKE 2 OR 3
HOURS AND WE,--YEAH, BASED ON
THE FULL DURATION HOW MUCH EACH
SESSION TAKES.
>>SO THAT BY ITSELF COULD BE
USED AS A NEW TOOL FOR
DIAGNOSTIC APPLICATIONS WITH
SUCH A HIGH SPATIAL PRECISION.
>>MM-HMM.
>>VERY EXCITING.
>>THANK YOU.
THANK YOU.
>>SO AT THE END DID THE
TEMPERATURE GO UP OR DOES THE
TEMPERATURE NOT GO UP?
>>SO FOR THE ANSWERS, THE
TEMPERATURE DID NOT GO UP.
SO THE IDEA IS I SHOW YOU DATA
WITH OPTICAL IMAGES O GENETIC
BECAUSE WE CAN REALLY RAMP UP
THE TEMPERATURE TO SEE, YOU KNOW
WHAT IS THE DETECTION THRESHOLD
AND WE CAN DETECT ROBUST SIGNAL
CHANGE ABOUT OUR OR 5-DEGREES,
SEE WITH HIGH INTENSITY WITH THE
LASER STIMULATION BUT FOR THE
ULTRASOUNDS, THE INTENSITY FOR
VERY LOW OPTICAL IMAGES O
GENETIC LASER, THERE'S NO
TEMPERATURE CHANGE, WE HAVE AN
ACRAZZY OF A POINT OR 2 FOR
DEGREES.
>>THANK YOU VERY MUCH.
>>[ APPLAUSE ]
SO NOW AS PART OF THE ORAL
SESSION, FIRST SPEAKER WILL BE
DR. KRISHNAMURTHY FROM EMORY
UNIVERSITY.
>>GOOD MORNING.
I WOULD LIKE TO THANK THE
ORGANIZING COMMITTEE FOR THE
OPPORTUNITY.
SO I HAVE--LET'S SEE.
I HAVE NOTHING TO DISCLOSE.
>>ALL RIGHT, SO, MY STUDIES
FOCUSED ON STROKE INDUCED
ASFACIA, PEOPLE THINK OF APHASIA
AS JUST A LANGUAGE DISORDER BUT
IT'S A COMMUNICATION DISORDER
AND IT PRESENTS IN UP TO 38% OF
ACUTE STROKE PATIENTS AND IT
PERSISTS EVEN IN CHRONIC STAGE
WHICH IS GREATER THAN 6 MONTHS
AND UP TO 60% OF THE
PARTICIPANTS.
SO IT'S NOT JUST AGAIN LIKE I
SAID LANGUAGE, IT AFFECTS
SPEAKING, SPEECH PRODUCTION,
COMP REHENGSZ WHICH IS
UNDERSTANDING AND ALSO READING
AND WRITING.
SO IT'S PRETTY DEBILITATING.
ALL RIGHT.
SO LET'S LOOK AT TDCS EVENTS IN
PATIENTS WITH APHASIA, THIS WAS
AN EARLY STUDY IN 2010, IT WAS
JUST 10 PARTICIPANTS AND I THINK
YOU FOUND IN SOMETHING IN HUMANS
AND INSPIRE HIM TO DO A LARGER
CLINICAL TRIAL AND THIS 1'S
PUBLISHED IN GERMANY IN 2018.
AND THIS 1 FOR THE ANALYSIS AND
AND THIS 1 IS TCS AS AN ADJUVANT
FOR SPEECH THIR ACTIVITIES AND
PROJECTS THAT'S ARE QUIRING MUCH
PROMISING RESULTS.
AND THEN THERE WAS ANOTHER PAPER
IN 2019 ON BRAIN STIMULATION
WHERE THEY ACTUALLY I THINK ON
THE SAME COHORT, 74% OF CHRONIC
APHASIA, SHOWED THAT TDCS, LEFT
TEMPERRAL LOCAL HAS SUPERIORITY
COMPARED TO THE SHAM.
SO AT THE END WOE DON'T HAVE
RANDOMIZED STUDIES OR TRIALS,
IT'S JUST MIXED RESULTS SO THAT
LEADS TO WHAT IS THE TDCS
MECHANISM WHICH IS STILL TRYING
TO UNDERSTAND.
WELL 1 CONCERNED WITH THE
REHABILITATION IS WE DO A
PRE POST DESIGN, BEHAVIORIAL,
POINT MEASURES, THEY'RE NOISY
AND THE PRE/POST DESIGN DOES
NONAPOPTOTIC THE CAPTURE THE
TIME.
AND ALSO WITH THE TDCS
INTERVENTION IS 20 MINUTES PER
DAY BUT THE PARTICIPANTS ARE
ACTIVELY DOING LANGUAGE IN 8 OR
9 HOURS SO THEY'RE DOING A LOT
OF DIFFERENT THINGS SO WE CAN'T
TRULY TELL WHAT IS THE TDCS
EFFECT.
SO 1 WAY THAT PEOPLE USE AND
NEUROIMAGING TO UNDERSTAND
MECHANISMS BUT WE KNOW THAT BOLD
IS NOT JUST [INDISCERNIBLE].
AND THE BIG QUESTION IS HOW DOES
THIS MONITOR EFFECTS IN BRAIN
PHYSIOLOGY INCLUDING
NEUROVASCULAR DISEASE WHICH IS
STROKE.
SO THE OBJECTIVE IS TO
INVESTIGATE THE MECHANISM AND
TARGETED ENGEAJMENT FOR
STIMULATION SITE AND THE
VASCULAR BIOMARKER IN POST
CHRONIC PATIENTS.
WE MONITOR EFFECTS, THE TARGET
ENGAGEMENT HERE FOR US WAS TO
UNDERSTAND WHEN WE HAVE A FIXED
STIMULATION SITE, AND WHEN THE
LESION IS HOW PROXIMAL IS THE
LESION AND HOW DOES IT IMPACT
THE MONITORED OUTCOMES AND
FINALLY PROGNOSTIC BIOMARKER CAN
BE USED CONCURRENT FMRIs FOR
DIAGNOSTIC BIOMARKERS FOR
PREDICTION, RIGHT?
SO THIS WAS, YOU KNOW AS YOU CAN
SEE--
>>RECORDING: PRESS YES.
>>I'M GOING THE WRONG WAY.
THE POINTER IS NOT WORKING, SO
HERE YOU CAN SEE WE HAVE NOW THE
PARTIC PLAN TO ANALYZE BY AGE
LYING IN THE SCANNER, WE HAVE
THE PHOTO BOX INSIDE, IN HERE WE
DESIGN A TRAPEZOIDAL TO THE
PARADIGM, WE STIMULATED F7, F8,
THE FRONTAL GYRUS, THIS IS THE
SYSTEM, AND HERE IS OUR PROTOCOL
GENERAL STUDY DESIGN AND WE HAD
CROSS OVER, THE SAME DISCIPLINE
CAME ON 2 DIFFERENT DAYS AND IT
WAS PLIENDED, RANDOMIZED AND
COUNTER BALANCED ACROSS THE
PARTICIPANTS.
RIGHT?
SO WE DID AUDITORY DECISION
TASK, THIS IS VERY IMPORTANT FOR
THE SPOKEN WORD COMP REHENGSZ
WHICH IS VERY IMPORTANT IN TERMS
OF LANGUAGE GAINS, OR TREATMENT
GAINS IN THESE PARTICIPANTS AND
OF COURSE WITH APHASIA AND I
JUST WANT TO PLAY A QUICK
30-SECOND VIDEO HERE SO THAT YOU
GUYS CAN SEE HOW THE TASK WENT.
OKAY, HERE WE GO.
SO I CAN EXPLAIN, THIS IS A
DECISION AUDITORY TASK, IT'S THE
SOUND TO PRACTICE THE INDEX
FINGER IF THEY RECOGNIZE A REAL
WORLD AND WE OF COURSE HAVE
PSEUDOWORDS, AND WE KEEP SEEING
THE + SIGN AND KEEP THEIR EYES
OPEN IN THE CONDITION IN TERMS
OF STATE AND FOR THE PROPERTIES
THEIR VOICE WAS RECORDED WITH
THE FEMALE VOICE AND VERY
NEUTRAL MIDWEST ACCENT.
ALL RIGHT, SO LET'S JUST KEEP
MOVING.
NOW LET'S LOOK AT PARTICIPANTS.
OUR FIRST GUY IS 66 YEAR-OLD
LESION IN THE FRONTAL GYRUS, 14
MONTHS AFTER STROKE AND
RELATIVELY I WOULD SAY HI,
MODERATE APHASE IMRA SEVERITY,
DISP IF YOU LOOK AT THIS GUY,
HOW DID HE DO, FOR WORDS, AS YOU
CAN SEE HERE, THIS IS IN SCANNER
BEHAVIORIAL PERFORMANCE WITH THE
ACTIVE STIMULATION JUST OVER THE
LESION, THERE'S IMPROVED ACRAZZY
AND ALSO THE REACTION TIME IS
NOT THAT DIFFERENT COMPARED TO
SHAM BUT STILL IT'S BETTER.
IN TERPS OF THE TASK ACTIVITY WE
SEE REALLY SUPPRESSED TASK
ACTIVITY, WE SEE INTERESTING
LANGUAGE AREAS, LEFT AND RIGHT,
AND BUT ANYWAY, SO, BUT IF YOU
LOOK AT VASCULAR AND NEURO, YOU
THIS DISPORTIONATE OF ACTORS SO
WE SEE THE CHANGES BUT MORE
IMPORTANTLY THE AREA IN THE
CURVE THAT IS THE BRAIN
ENERGETICS SO WE CAN SEE THAT IS
A SIGNIFICANT CHANGE FROM ACTIVE
TO SHAM, SO THE CONTRAST HERE IS
ACTIVE FOR SHAM FOR THE WORD
CONDITIONS.
WHAT ABOUT NONWORDS.
AGAIN, SAME GOI, PHYSIOLOGY IS
THE SAME BUT IN TERMS OF
BEHAVIORIAL PERFORMANCE WITH
THIS GUY, THE ACCURACY WAS NOT
THAT DIFFERENT DURING ACTIVE
STIMULATION BUT REACTION TIME
SIGNIFICANTLY DECREASED.
OKAY, THEN WE TOOK, WE DID THE
RESTING STATE.
WE SEE THAT F7, F8 WHICH IS THE
ELECTORATE PLACEMENT AND ALSO AS
YOU TOOK THE GUY FROM THE
PREVIOUS 1, THE SIGNIFICANT
LANGUAGE ACTIVATION AREAS FROM
THE TASK AND WE TOOK THOSE SEED
AREAS WHERE WE SEEDED FROM THAT,
THOSE SEEDS AND THEN WE DID THE
CONNECTIVITY ANALYSIS, AGAIN,
YOU SEE THAT WE SEA SUPPRESS
CONNECTIVITY ESPECIALLY WHEN
YOU'RE STIMULATING RIGHT OVER
THE LESION.
OKAY?
SO NOW LET'S LOOK AT A DIFFERENT
PARTICIPANT, THIS GUY IS 59
YEAR-OLD NOW THE LESION IS STILL
IN FRONTAL BUT IT'S MORE IN THE
PRESENTERAL GYRUS, A BIT MORE
ANTERIOR, 13 MONTHS AFTER STROKE
BUT HE'S A REALLY HIGH
FUNCTIONING GUY, HE IS REALLY
HIGH FUNCTIONING.
SO IF WE LOOK AT THIS GUY, WE
LOOK AT THE BEHAVIORIAL
PERFORMANCE THE REACTION TIME TO
BE ACCURATE TO RESPONSE NOT THAT
DIFFERENT BUT IN THE ACCURACY,
TOO, IN TERMS OF THE PAST
ACTIVITY, AGAIN IT'S SUPPRESSED
DUE TO ACTIVE TDCS, BUT IF YOU
LOOK AT THE HEMODISCIPLINARY
MEDICARE AND MEDICAIDIC
RESPONSE, THERE'S A SIGNIFICANT
CHANGE IN THE DISTORTION, THE
[INDISCERNIBLE], YOU CAN CLEARLY
SEE HERE IN THE, IN HERE, TOO,
JUST BECOMING PRETTY FAST.
IF YOU LOOK AT THE NONWORDS FOR
THE SAME GUY IN TERMS OF
PHYSIOLOGY AGAIN IT'S THE FIRST
ACTIVITY FOR TASK, WE CAN SEE
THE LESION HERE BUT THEN AGAIN
THE FULL MAX MA, AGAIN IS A
SIGNIFICANT DECREASED WHICH IS A
DISPERSION PARAMETER BUT THE KEY
THING IS PETRESSABLE
HAIEVERRIALLY, THE ACCURACY IS
MORER LEFT THE SAME BUT THE
REACTION TIME IS REALLY GOING
DOWN IN RESPONSE TO THE ACTIVE
TDCS.
ALL RIGHT, SO IN THE END WE DID
THE SAME THINK THIS FOR RESTING
STATE CONNECTIVITY FROM F7, F8
AND LANGUAGE AREAS HERE WE SEE
INCREASED CONNECTIVITY WHICH WE
HAD SEEN BEFORE AND PREVIOUS
WORKS, TOO, WE EXPECT THAT WITH
ACTIVE TDCS INERTIA PRIME THE
NETWORK FOR THE TASK, BUT THE
INTERESTING PART IS THE TASK
ACTIVITY WAS SUPPRESSED IN
RESPONSE TO ACTIVE TDCS, BUT
THERE IS RESTING STATE ACTUALLY
INCREASED; OKAY, NOW MY LAST
PARTICIPANT HE HAD LESION IN THE
TEMPORAL GYRUS, 55 YEAR-OLD BUT
THIS GUY'S A LITTLE BIT ON THE
LOWER END OF THE MODERATE SIDE
OF THE EFFICIENT SEVERITY SO
HE'S HIGH FUNCTIONING, SO IF YOU
LOOK AT THIS GUY, WHEN WE
STIMULATE THE SAME F7, F8, NOW
THERE'S NOT MUCH DIFFERENCE IN
TERMS OF BEHAVIORIAL ACCURACY OF
THE REACTION TIME BUT THERE'S A
HUGE RESPONSE ACTIVITY IN
RESPONSE TO THE ACTIVE TRKTS
DCS, AND YOU CAN CLEARLY THAT
THE DIFFERENCE BUT THE VASCULAR
SIDE IS NOT CHANGING THAT MUCH.
OKAY, AND THE SAME GUY FOR THE
NONWORDS THE PHYSIOLOGY IS THE
SAME, PHYSIOLOGICAL RESPONSE,
ACTIVITY, AGAIN THE AREA UNDER
THE CURVE IS SIGNIFICANTLY
CHANGING NOT THE VASCULAR SIDE
BUT THE INTERESTING PART IS THAT
THE BEHAVIORIAL SIDE, NOT MUCH
DIFFERENCE MAYBE THE SHAM WAS
BETTER FOR ACCURACY BUT
NONVERSUS HARDER SO HE TOOK
LONGER TIME TO GET C-TYPE
LECTINS ANDERATE RESPONSE
ESPECIALLY UNDER ACTIVE TDCS.
AND IF YOU LOOK AT THE RESTING
STATE, AGAIN WITH THIS GUY,
WHERE THE LESION WAS DISSAL FROM
THE STIMULATION SITE, AGAIN WE
SEE THESE INCREASED CONNECTIVITY
IN THE RESPONSE TO THE F7, F8
STIMULATION.
SO, THEN YOU WANTED TO LOOK AT
THE STATE IN ORDER OF EFFECT.
SO AGAIN, I'M KIND OF GOING BACK
TO OUR SET UP HERE, OUR STUDY
DESIGN SO WE HAD RESTING STATE
WITH NO TDCS, THE TDCS OFF ON
BOTH DAYS AND THEN WE HAD THE
RESTING STATE DURING TDCS, WHEN
WE WAS ON SHAM SO WE WANT TO
LOOK AT THE INTERCESSION AND
INTRA SESSION DIFFERENCES SO
BASICALLY HERE I'M SHOWING THE
ORDER, AND WE HAD 1 WITH SHAM,
WE HAD S3 WAS ACTIVE FOLLOWED BY
SHAM.
THE DAYS APART MAKERS AND A NOTE
THAT IT WAS ONLY 3 DAYS, SO WAWE
SEE HERE IS THAT MORE OR LESS, I
MEAN IT'S S2 AND S3, PROBABLY
S2, THERE'S NO SIGNIFICANCE BUT
WE SAW SIGNIFICANT DIFFERENCE
FOR S1 DURING THE--
>>MAYBE 2 MINUTES.
>>OKAY, AND AND S3, SO IF YOU
LOOK AT THAT, SHOW OTHER
DIFFERENCES, SO WHAT WERE THE
SUMMARY OBSERVATIONS IN TERMS OF
MECHANISMS WE SEE THAT ACUTE
REALTIME TDCS STIMULATION DOES
NODULATE NEURAL AND VASCULAR
SIDE.
THE TYPE DOES INFLUENCE THE TDCS
EFFECTS BOTH IN PHYSIOLOGY AND
BEHAVIOR, WHAT WE ALSO SAW WHAT
WAS ORDER OF STIMULATION BETWEEN
ACTIVE AND SHAM AND BRAIN STATE,
DOESN'T GO WITH THE ACUTE TDCS
MODALATORY RESTING STATE.
IN TERMS OF TARGETING
ENGAGEMENT, PARTICULARLY FROM
S1, WE--YOU SAY THAT YOU KNOW
STIMULATING OVER THE LESION, IT
MIGHT BE BENEFICIAL ON MONDAY
DOCTOR [INDISCERNIBLE] SHOWED
THAT WITHLET DIFFERENT MODALITY
WHICH IS TMS, WHICH TOLD US THE
TIGR MRI, THIS IS THE
PREKAFITATIONAL AREAS, YOU KNOW
WE MAY NOT WANT TO ABOUT THE
TISSUE IN THE LESION, BUT THIS
LESION BASED ON BASE LINE
CHARACTERISTICS, SO IN TERMS OF
BIOMARKER DEVELOPMENT WE SEE
DISPERSION IN THE AREA WHICH
OCCUR PARAMETERS ARE PRETTY
SENSITIVE AND OF COURSE RESTING
STATE, TOO.
SO, MY LAST SLIDE.
WHAT ARE THE LIMITATIONS AND OUR
FUTURE WORK, SO THIS WAS A PILOT
AS YOU SAW, BUT THE APPROACH IS
PRETTY INFORMAIVE IT TOWARDS
PERSONALIZED APPROACH WHICH IS
VERY BIG IN STROKE
REHABILITATION.
THERE WAS JUST 3 DAYS IN BETWEEN
ACTIVE AND SHAM, PROCEEDING SHAM
IT MAY HAVE IT CLEARED OVER
PHYSIOLOGICAL EFFECTS DUE TO
POST INAPTAMERRIC INTEGRATION
TAKES TIME, AND MAYBE THAT'S WHY
YOU KNOW SOME OF THE STATE
EFFECTS THAT YOU SAW IN S3 COULD
BE COMING FROM THAT.
IN TERMS OF, YOU KNOW THE NEWER
METABOLITES, YOU KNOW WE
PUBLISHED EARLIER THIS SUMMER IN
AGINGSINGS THAT GABBA DPLIEWT
MATE HAS A STRONG INFLUENZ ON
THE NEURAL VASCULAR EFFECTS, OF
TASK, SO I THINK TESTIMONY BE
VERY INTERESTING TO LOOK AT
THAT, IN APHASIA AND ALSO IN
RESPONSE TO TDCS, PARTICULARLY
TDCS, AND OUR ELECTRODES WERE
PRETTY SUFFICIENT, AND I WILL
ALWAYS SHAMS AND ALSO THE TISSUE
WITHIN THE TISSUE AND I
MENTIONED THAT AND MAYBE DEVELOP
MORE SENSITIVE BIOMARKERS FOR
ACCOUNTING FOR EFFECTS.
OKAY.
WITH THAT I THANK YOU FOR YOUR
ATTENTION AND OUR FUNDING
SOURCE.
THANK YOU VERY MUCH.
>>[ APPLAUSE ]
WHY CAN TAKE 1 QUESTION.
>>DPRAIT TALK, IN OTHER MODELS
I'M SEEING IN STROKE, THE TIME
WHEN IS YOU DO THE STIMULATION
RELATIVE TO THE INJURY AND
WONDERING IF YOU HAVE EXPLORED
THAT TIME PARAMETER FROM A BASIC
SCIENCE TIME POINT PLASTICITY
VERY SPECIFIC WHEN IT OPENS UP
POST INJURY SO LOOKING AT THAT
COULD HELP WITH AUG.
METROPOLITANNING THAT RESPONSE?
>>I AGREE WITH YOU AND
PARTICULARLY IN CHRONIC PHASE,
IT'S TYPICALLY CONSIDERED THE
WINDOW AND SMALL AND WE DID
RECORD HOW MANY MONTHS POST
STROKE, WE JUST HAVE TO CODE IT
OUT AND SEE HOW THE EFFECTS HAVE
CHANGED BUT THAT'S A REALLY GOOD
POINT.
>>GOOD, NOW WE CAN MOVE--THANK
YOU VERY MUCH.
[ APPLAUSE ]
OUR NEXT SPEAKER IS GOING TO BE
DR. LIPENG, NING, FROM HARVARD.
>>THANK YOU FOR THE
INTRODUCTION.
I HAVE NOTHING TO DISCLOSE.
I THINK WE HAVE MANY PEOPLE TALK
ABOUT RTMS FOR DEPRESSION.
FMRI IS THE BASED WITH RESTING
STATE AND HAD BEEN USED FOR
FINDING TARGET FOR RTMS
TREATMENT.
CAN YOU SELECT ROI, OF THE
SINGULATE OR LABEL FOR A NETWORK
TO DEFUND THE FC MAP, THEN THE
BRAIN REGION, LIKE THE DLPFC,
WHICH IS IN THE NETWORK IS
FINDING THE TARGET.
THE TARGET FOUND THE GROUP
[INDISCERNIBLE].
THE UNDERLYING IDEA THAT THIS
CAN BE A WINDOW TO THE
UNDERLYING DEEP BRAIN REGION FOR
THE UNDERLYING NETWORK, BUT THEN
THE NEUTRAL PATHWAY HAS BEEN
[INDISCERNIBLE] NOT REAL LEGAL
WELL UNDERSTOOD.
SO WE LOOK INTO THIS PROBLEM
WITH THE WORK TRYING TO
UNDERSTAND THE STRUCTURE AMILLIO
POSSIBILITIES UNDERLYING GREATER
THAN THE RTMS ESTIMATION, SO
WITH [INDISCERNIBLE] BUNDLE THAT
CONNECT THE LATERAL PFC AND
ENTER MEDIAL PFC FOR THE
[INDISCERNIBLE] REGION,
[INDISCERNIBLE] AND THE FAB
RIDICULOUS GOES THROUGH THE
OTHER BRAIN [INDISCERNIBLE] AND
ALSO CONNECTION TO
[INDISCERNIBLE] SINGULATE.
I THINK THE LAST IS NOT REALLY
[INDISCERNIBLE] BUT THE LAST 1
THIS 1'S PRETTY INTERESTING.
AS CAN YOU SEE THERE'S NO
CONNECTION FROM THE DLPFC EVEN
THOUGH THERE'S STRONG FUNCTIONAL
CONNECTIVITY.
AND WE LOOKED AT THESE IN A LOT
OF DATA IN THE HIGH QUALITY
NECKANISM DATA, [INDISCERNIBLE]
AND THEN WE LOOK INTO THE
LITERATURE ABOUT TODAYS AND THEY
INJECT INTO THIS REGION AS A
SINGULAR SUBJECT UNIT.
AND WE STUDY [INDISCERNIBLE]
DATA AND BEFORE RTMS DATA FOR
ENTIRE SESSIONS AND I THINK IN
THE [INDISCERNIBLE].
I THINK THE MAJOR CHANGES ALL
CONNECT TO THE INTERMEDIATE PFC.
SO I THINK IT INCREASED
CONNECTION IN THESE CONNECTIONS
TO THE PFC AND ALSO INN CREASE
THAT WAY INTO MULTIPLE FIBERS
AND ALSO REDUCE THE
[INDISCERNIBLE].
SO AS INDICATE THAD MAYBE THE
PERIVASCULAR SPACE INCREASE FOR
THE [INDISCERNIBLE] THAT WAS
TALKED YESTERDAY AND MAYBE FIBER
INTEGRATED MEANS IT'S MAYBE OR
[INDISCERNIBLE] LEAD TO THE
INCREASE IN THE [INDISCERNIBLE].
AND ALSO WE FOUND THAT EVEN
THOUGH THE LATERAL CONNECTION,
IS LESS SIGNIFICANT CHANGES, BUT
THE CHANGES MORE RELEVANT TO
CLINICAL OUTCOME, IT MEANS THAT
MORE IMPROVEMENT IN THE LATERAL
CONNECTION TO LATERAL PFC
INDICATES BETTER TREATMENT AND
OUTCOME AND ALSO MORE REDUCTIONS
IN THE [INDISCERNIBLE].
SO THIS IS REALLY INTERESTING
BUT STILL NOT ANSWER THE
QUESTION FROM A CLINICAL
PRACTICAL POINT.
SO WE TARGET WHICH PATHWAY WOULD
WE USE AS A TARGET?
SO I THINK THIS STUDY, SO WE
LOOKED FURTHER INTO THE DATA
USING THE ELECTROFIELD MODELING,
SO THIS IS MORE DETAILS ABOUT
THE DATA APPLICATION, SO WE HAVE
21 PATIENT WHO SUBMIT WITH THE
OTHER AND THEY'RE ALSO WITH THE
FOOD SESSION 36 SESSION WITH THE
HIGH FREQUENCY TO THE LEFT AND
USING SUBJECT SPECIFIC ACTUALLY
USING SUBJECT WITH THIS, SO THIS
JUST INDICATES THAT THE REGION,
AND ALSO THIS IS SHOWING THE WAY
WE [INDISCERNIBLE] SIMILAR TO
[INDISCERNIBLE] PROPOSE THE
METHOD AND FUND TARGET FOR
[INDISCERNIBLE] SUBJECT.
THE BUT THE TARGET FOR THAT MAY
NOT BE THE TARGET THAT WE
ACTUALLY STIMULATE BECAUSE THE
DIFFERENT DISTRIBUTION FIELD TO
UNDERSTAND THE EFFECTIVE TARGET
THAT WE HAVE SO WE APPLY SIM NIB
TO SIMULATE ELECTRICAL FIELD
BASE EDUCATIONAL ON THE MRI, AND
THEN WE LOCALIZE THE ROSENT WITH
[INDISCERNIBLE] OF THE FIELD,
THAT'S CONSIDERED EFFECTIVE
SUBMISSION TARGET.
USING THE ALGORITHM WE CAN MAP
ALL THE TARGET THE SAME AND
OVERLAY ON TOP OF THE
[INDISCERNIBLE] AREA WHERE WE
SHOW THE DISTRIBUTION OF TARGET.
YOU CAN SEE THAT MULTIPLE TARGET
IS AROUND THE [INDISCERNIBLE],
THAT IS THE TRADITIONAL RPFC
REGION BUT SOME TARGETS WILL BE
FURTHER AWAY BECAUSE THE
INTERSUBJECT WHERE WE HAVE
[INDISCERNIBLE] THAT.
SO WE ALSO DISTRIBUTION OF THE
TARGETS FOR SOME OF THE ADVANCE
IN THE ISOTOPIC WALL HAVE EQUAL
DISTANCE TO THE FIBER, TO THE
TARGET.
SO THEN WE CALCULATED THE
CORRELATION FROM THE DISTANT OF
THE FIBERS [INDISCERNIBLE].
SO THIS IS THE MAIN RESUMMIT.
WE FOUND THAT SHOULDER DISTANCE
TO THE CONNECTION TO SUBUNIT
SINGULAR RUNNING 9, SO IT'S
BASICALLY TO THE MEDIAL PART AND
YOU GET BETTER THAN OTHERS SO
THE WAY WE DID IT IS USING
HIERARCHICAL ANALYSIS AND FORCED
TO A PORTION FROM THE SEVENTH
MAJOR FIBER BUNDLE AND DO THAT
TO THE SMALLER FIBER BUNDLE TO
LOCALIZE MORE SPECIAL FIBER,
BECAUSE THERE'S SO MANY OF
THESE, I THINK THE
[INDISCERNIBLE] IS INTERESTING
BUT NOT SIGNIFICANT ENOUGH TO
CLAIM IT TO SLIDE
[INDISCERNIBLE] BUT IT'S STILL
INTERESTING PERMITTING AND ALSO
I THINK SOME OF YOU MAY BE
INTERESTED IF THERE ARE
SIGNIFICANT CULTURE WITH IN
FIELD INTENSITY [INDISCERNIBLE]
WE DIDN'T FIND ANY INFORMATION
WITH THE INTENSITY SO WE
CALCULATE THE INTENSITY OF THE
FIBER BUNDLES AND ALSO AROUND
THE REGION BUT WE DIDN'T SPEND
ANY OR DATA AND SO THIS IS JUST
1 EXAMPLE OF HOW THIS CONNECTION
LOOKS LIKE FOR 1 SUBJECT.
I THINK THAT'S OUR MAJOR RESULT
SO BASICALLY WE DISCUSS
ULTIMATELY FUTURES IN MULTIPLE
FIBER PATHWAYS AND ALSO IF
YOU'RE MODELING AND WITH THE
TARGET.
AND THE TARGET, I THINK--SO
BEASKLY THE RESULTS FROM OUR
STUDY TO THE MEDIAL PART OF
[INDISCERNIBLE] BUT TALK THAT
DR. ELIZABETH PRESENTED ON
MONDAY THAT'S CONNECTION BETWEEN
SGC KD--SALLY BA AND SO THAT'S
FROM THIS PAPER, THIS IS JUST
THE COMPARISON BETWEEN THE 2
FIBERS SO THEY ARE REALLY
RELATED SO FOR 9 AND 10, NEXT TO
EACH OTHER AND ALSO CONNECTION
TO THE INTERMEDIAL PART.
AND ALSO WE LOOK INTO THE MONKEY
LITERATURE THAT THIS STUDY THAT
INJECT [INDISCERNIBLE] FROM
EITHER 9 OR 10, THEY OFFER TO
[INDISCERNIBLE] 25 SO I THINK
IT'S VERY INTERESTING.
BUT I THINK ALSO WE NEED TO
RETHINK THAT WE CLARIFY THE
FIBER BASED ON THE CENTRAL
ARCHITECTURAL STRUCTURE OF THE
REGION BUT MAYBE IF THEY BELONG
TO THE SAME FUNCTION, THEY HAVE
THE SAME FUNCTIONAL, MAYBE CAN
YOU BE AT THE GROUP TARGET.
SO, BUT ALSO OUR STUDY IS ALSO
IMAGED BY THE NUMBER OF
SUBJECTS.
WE ARE LOOKING FOR MOST DATA, I
THINK MOST LIKELY KNOW IF WE
HAVE ANY DATA RELATED AND ALSO,
I THINK FROM THIS I SAW MANY
TALKS USING FMR, AND TO A LIST
OF [INDISCERNIBLE] FM R STUDY
BECAUSE IT DOES PROVIDE
DIFFERENT INFORMATION TO
UNDERSTAND UNDERLYING NETWORK.
THAT'S ALL FOR MY TALK.
CAN YOU E-MAIL ME IF YOU HAVE
ANYY REQUESTS.
THANK YOU.
[ APPLAUSE ]
>>THANK YOU VERY MUCH, WE CAN
TAKE 1, 2 QUESTIONS.
IF THERE IS A QUESTION.
>>OH, SORRY GO AHEAD.
>>VERY NICE WORK OF COURSE THE
IT'S A VERY DIFFICULT PROBLEM.
WE CAN ALWAYS RELAX THE FIBER
PARAMETERS AND GET ARE DIRECT
CONNECTIONS ABOUT YOU DOESN'T
MEAN THERE'S ACTUALLY
CONNECTIONOT OTHER END YOU COULD
NOT FIND THOSE CONNECTIONS THAT
ALSO DOESN'T MEAN THAT THERE
AREN'T CONNECTIONS BUT YOU ALSO
WITH NEUROANATOMY SO WHAT IS
THEIR EXPECTATION?
DO THEY EXPECT A DIRECT
CONNECTION AS A POSSIBILITY?
SO IS THERE A LIKE A SEARCH
ACTUALLY TFERREDS THE DIRECTION
ALSO?
OR I MEAN LIKE A--IS
[INDISCERNIBLE] VALUABLE TO
ACTUALLY SPECULATE THAT THAT
COULD BE A DIRECT PATHWAY ALSO?
WHAT'S YOUR OPINION?
>>YOU MEAN THE DIRECT
CONNECTION FROM THE
[INDISCERNIBLE] TO SUBJECT
STIMULI?
>>YEAH.
>>OUR DATA WE DIDN'T FIND THAT.
REALLY HIGH RESOLUTION MR AND
ALSO THE MONKEY LITERATURE, FOR
1 CITATION, THEY INJECT FROM THE
[INDISCERNIBLE] PROGRAM FOR THIS
AND DIDN'T GO TO [INDISCERNIBLE]
SO I THINK THAT'S VERY
CONSISTENT TO OUR RESULTS.
SO THESE ARE THE CONNECTIONS,
INDIRECT CONNECTION FROM OTHER
PATHWAYS OR FROM OTHER CORTICALE
TO CORTICALE PATHWAY THAT CAN
NOT BE [INDISCERNIBLE].
SO WE ALSO WORKING ON HIGH
RESOLUTION AND SUPER OFFICIAL
BUT TRACKING SO WE GET MORE
DETAILS NETWORK STRUCTURE FOR
THAT RETURN.
>>OKAY, THANK YOU.
>>MAYBE IF I CAN JUST ADD 1
COMMENT.
WHEN WE DO FOCUS ULTRASOUND
IMAGING IN THE INTERNAL CAPSULE,
WE DO ACTUALLY GET THE SAME
FIBERS YOU'RE GETTING TO 9 AND
10 EMPLOY I GUESS MOST PAPERS
ARE PREDICTING THE IMPROVEMENT.
SO LESIONING THE FIBERS GO IN
THERE ALSO WORKS, --I GUESS.
>>THANKS.
OKAY.
>>THANK YOU AGAIN FOR THE NICE
TALK.
>>[ APPLAUSE ]
AND THEN THE LAST SPEAKER WILL
BE DR. ZHAI FROM THE NATIONAL
INNSITUTE ON DRUG ABUSE.
YOU CAN STARLIGHT THE VIDEO.
>>I HAVE NOTHING TO DISCLOSE
FOR MY TALK TODAY, HELLO I'M
TIANYE, ZHAI FROM THE NATIONAL
EN--STRATEGIESITUTE ON DRUG
ABUSE AND MY TALK TODAY IS
NEUROIMAGING BASED TARGET
PRESCREENING FOR TARGET DESIGN,
BASED ON YEARS OF HUMAN RESEARCH
ON THE HUMAN BRAIN, OR SO CALLED
READING FROM THE BRAIN, WE ARE
NOW ENTERING AN ERA OF BACK
TRANSTHRAIGZ TO THE HUMAN BRAIN
OR WRITING TO THE BRAIN WITH A
AID OF LIST OF TRANSCRANIAL
STIMULATION TECHNIQUES SUCH AS
THE TMS, TDCS, TACS, TAUS, ET
CETERA THAT WE HAVE BEEN TALKING
ABOUT OVER THE PAST FEW DAYS.
THE NAWP INVASIVE NATURE OF
THESE TECHNIQUES MADE THEM
PROMISING TOOLS TO TACKLE WITH
DIFFICULTIES IN A TREATMENT OF A
WIDE RANGE OF NEUROSICKIATRIC
DECS SUCH AS MAJOR DEPRESSIVE
DISORDER, OBSESSIVE COMPULSIVE
DISORDER AND SUBSTANCE USE
DISORDER.
DUE TO THE OVERARCHING WROAL
ROLE IN GOVERNING MANY COGNITIVE
AND EFFECTIVE PROCESSES, THE
PRECORTEX, SUCH AS THE PFC, AND
THE OFC AND THE VFC HAS GAINED
ATTENTION AS TARGETS OF THE HOW
HOWEVER, LIKE THE HUMAN OFC,
THESE ARE USUALLY ANATOMICALLY
LARGE AND FUNCTIONALLY
HETEROGONEIOUS, THIS MEANS IF
YOU STIMULATE DIFFERENT REASON
YOJS, YOU'RE LIKELY TO,A CHIEF
DIFFERENT THINGS, ALTHOUGH
THEY'RE ALL CALLED
OFC STIMULATION.
IT HAS BEEN DEMONSTRATE THAD
EACH WITHIN THE CONCEPT OF
DFLCSOMULATIONS, DIFFERENT
ACTIONS WERE ASSOCIATED WITH
EFFICACY FOR DEPRESSION.
AND WE KNOW THAT IN NONEVASIVE
STIMULATION, IT'S A CRUCIAL
DETERMINANT FOR THE TREATMENT
AND EFFECTIVENESS AMOUNT OF
PRIMER TO SPACE, BUT MANY
NEUROMODDULATION BASE AND
CLINICAL STUDIES LACK COMPELLING
JUSTIFICATIONS IN SELECTING THE
ACTUAL LOCUS OF A REGION FOR THE
STIMULATION TARGET.
WE HAVE 3 FOR THE DLPFC, AND
DRIVING FROM THE CLASSICAL 1020
SYSTEM OR SOMETIMES IT CAN BE
EVEN SIMPLER THAN THAT JUST TO
USE COORDINATES FROM A PREVIOUS
PUBLISHED LITERATURE.
IN SEARCHING FOR THE EFFECTIVE
TREATMENT TARGETS OF A SPECIFIC
DISORDER, THE MOST INTUITIVE WAY
IS TO SEARCH WITHIN INTERESTED
AREA DIRECTLY WITH THE CLINICAL
TRIALS IN THIS CASE, SAY WE HAVE
DIFFERENT BRAIN SIDES TO BE
TESTED FOR EFFICACY.
EACH SIDE REQUIRES A CLEANICAL
TRIAL WITHIN PARTICIPANTS, THAT
IS A TOTAL OF PARTICIPANTS
NEEDED TO EVALUATE THE
TREATMENT'VE CASSIE UNDER
CLINICAL SETTING.
PLUS THE OTHER FACTORS IN HUGE
PRIMARY SPACE, THIS DIRECT
STRATEGY IS FINANCIALLY COSTLY
AND TIME CONSUMING TO AN EXTENT
OF BEING VIRTUALLY IMPOSSIBLE.
IT IS HOWEVER POSSIBLE TO USE
THE FUNCTIONAL IMAGING SUCH AS
FMRI TO CHARACTERIZE FUNCTIONAL
FEATURES OF MULTIPLE RIs TO
IDENTIFY LOCI AND FUNCTIONAL
SUCKERITS THAT ARE MOST RELEVANT
TO DISEASE RECOVER EXPE
TREATMENT, AND MIGHT BE
PRIORITIZED IN TESTING EFFICACY
IN CLIN CAM SETTINGS AS A
STIMULATION TARGET.
THEREFORE WE PROPOSE THE 2 STAGE
APPROACH FOR NEURAL MODULATION
BASED ON TRIM AND DEVELOPMENT, A
STAGE 1 THAT INVOLVES THE
EXPLORING RIs FOR THEIR
RELEVANCE TO A SPECIFIC DISEASE.
AND A STAGE 2 OF TESTING ONLY A
FEW.
MOST RELEVANT BRAIN LOCATIONS
WITH A CLINICAL TRIALS FOR
EFFICACY.
THIS WILL GREATLY REDUCE THE
TIME AND EFFORT NEEDED FOR
TARGET OPTIMIZATION, IN
NEUROMODDULATION BASED CLINICAL
INVESTIGATIONS TO A FEASIBLE
LEVEL.
SO NEXT I WILL BE FOCUSING ON
DEMONSTRATING THE NEUROIMAGING
BASE TO STAGE 1 WITH THE
EXEMPLAR OF THE OFC STIMULATION
FOR COCAINE DISORDER.
THE COCAINE USE DISORDER HAS
MANY OTHER FORMS OF ARK DICTION
IS A HIGHLY REFRACTORY
PSYCHIATRIC DISEASE WITH A
HIGHER LAPSE RATE POST TREATMENT
EACH FOR THE TREATMENT SEEKING
PATIENTS, THEREFORE OUR STAGE
GOAL HERE IS TO IDENTIFY LOW C 1
THE ROI THAT COVERS THE ENTIRE
OFC THAT RELATE THE MOST TO
COCAINE RELAPSE.
IN ORDER TO DO SO, 2 COHORTS
WERE INVOLVED COHORT 1
DISCOVERED AS A RESTING DATA
FROM 43 TREATMENT SEEKING CUD
PATIENTS WERE SCANNEDDA THE END
OF A 30 DAY PATIENTS SOCIAL
TREATMENT PROGRAM AND FOLLOWED
UP FOR UP TO 6 MONTHS.
ALSO INVOLVE SUGGEST A COHORT 2
OR INDEPENDENT VALIDATION
COHORT, SIMILARLY, THIS COHORT
OF A 36 PARTICIPANTS WERE
SCANNED AT THE END OF 2-4 WEEK
IN PATIENT TREATMENT PROGRAM FOR
RESTING STATE FMRI AND FOLLOWED
FOR UP TO 90 DAYS POST TREATMENT
FOR COCAINE RELAPSE.
REGARDLESS OF THE TECHNICAL
DETAILS GENERALLY WHAT WE DO IS
FOR EACH OF THE ROIs, WE
COMBINE WHOLE BRAIN FUNCTIONAL
CONNECTIVITY AND RELAPSED DATA
WITH THE MODELING TO GENERATE
PREDICTION MODELS, SIFORT WE
PREDICT ANALYSIS ON COHORT 1, ON
THE CROSS VALIDATION LOOP AND
THEN WE USE COHORT 2 BEFORE
EXTERNAL FOUNDATION.
THE ANALYSIS CONDUCTED FOR ALL
20 ROIs, FOR MEDIA TO
BILATERALLY.
TWO OUT OF THE 20 RIs WE
TESTED WERE IDENTIFY AS
SIGNIFICANTLY COCAINE RELAPSE
WITHOUT THEIR FUNCTIONAL
CIRCUITS.
BOTH ON THE LEFT LATERAL SIDE OF
THE OFC.
THESE ARE REFERRED TO AS
PREDICTIVE ROI 1 APPROXIMATE 2
HERE AND AFTER.
AFTER EACH OF THE ROIs, 2 SETS
OF FUNCTIONAL CIRCUITS THAT
UNIQUELY CONTINUED TO COCAINE
RELAPSE WERE ALSO IDENTIFIED, A
SET OF PROTECTIVE CIRCUITS WHICH
MEANS THE STRONGER FUNCTIONAL
CONNECTIVITY AND THE LESS
LIKELIHOOD OVERLAPS AND A SET OF
RISK CIRC ARE UTRS WHICH MEANS
THE STRONGER FUNCTIONAL
CONNECTIVITY, THE HIGHER
LIKELIHOOD OF RELAPSE, DURING
THE FOLLOW UP, BUT IN ORDER TO
MINIMIZE THE OVERLAPPED VARIANCE
EXPLAINED BETWEEN PREDICTION
MODELS FROM THE 2 ROIs, WE
COMBOYNE THOSE FROM THE ROIs
AND SELECTING TERMS IN THE
COMBINATION AND BUILD THE FINAL
PREDICTION MODEL THAT INCLUDE
THE RISK INDEX OF THE REDICTIVE
RO-1 AND THE BRO DICTIVE INDEX
OF ROIs 2 OF 91.4%.
WE THEN APPLY OUR REFINED FINAL
PREDICTION MODEL ON COHORT 2 FOR
INDEPENDENT VALIDATION WHICH
YIELDED REASONABLY ACCURATE
PREDICTION OF RELAPSE AT 75.9%
ACCURACY.
FINALLY WE ALSO CONDUCTED A POST
HOC ANALYSIS BY COMBINING ALL
DATA FROM 2 COHORTS AND
CLUSTERING THEM ON THE
PROTECTIVE RISK PLAYING FROM THE
FINAL PREDICTION MODEL.
SIX TYPES WERE IDENTIFIED.
FOR EXAMPLE, CLUSTER 1 AND 2 ON
THE LOWER CORNER AND HIGH
PROTECT AND I HAVE LOWER RISK
INDICES, WHICH IS THE LONGEST
BASE FOR RELAPSE AS SHOWNOT BAR
PLOT ON THE RIGHT.
FOR QUICK DISCUSSION USING FMRI
AND COST REGRESSION BASED
PREDICTION MODELS WE WERE ABLE
TO IGENETICALLYIFY 2 OUT OF
HUMAN, ROIs THAT ARE HIGHLY
RELEVANT TO COCAINE RELAPSE,
WITH THE FUNCTIONAL CIRCUIT.
THESE COULD BE TREATED AS
POTENTIAL STIMULATION TARGETS TO
BE FURTHER TESTED WITH CLINICAL
TRIALS.
THE IDENTIFIED FUCHGZAL CIRCUITS
SERVING RISK FACTORS WAS
RELAPSED NOT ONLY PROVIDE A
SYSTEM LEVEL NEURAL MECHANISM
FOR THEIR RELEVANCE TO COCAINE
RELAPSE BUT MAY ALSO SERVE AS A
POTENTIAL UNDERLYING MECHANISM
NEAR NEURAL MODULATION TREATMENT
TO TAKE EFFECT.
ONE THING THAT GAVE US MORE
CONFIDENCE IN THIS IS OUR
PREVIOUS STUDY USE UTILIZING A
SIMILAR MODELING TECHNIQUE
INVESTIGATED [INDISCERNIBLE] AND
IDENTIFIED AS 3 HIGHLY RED
ROIs, AND THE 1 ON THE LEFT IS
VIRTUALLY THE SAME AS THE ACTUAL
RTMS SIMULATION TARGET THAT
SHOWED PROMISING TREATMENT IN
THE ADVOCACY IN AN OPEN LABEL
PILOT STUDY TREATING COCAINE
ADDICTION, THIS IS THE PERFECT
EXAMPLE OF THE POTENTIAL
APPLICATION IN THE MODELING
APPROACH IN THE FIRST STAGE FOR
TARGET PRESCREENING WHICH CAN BE
USED TO GUIDE EXPERIMENTAL
DESIGNS IN THE SECOND STAGE FOR
VALIDATION WITH CLINICAL TRIALS.
AWLTS POTENTIAL SUBSTIEPS OF DEC
CAN BE CHARACTERIZED WHICH COULD
BE UNDERLYING A CALMLY OBSERVED
VARIANCE IN INDIVIDUAL
RESPONSIVENESS TO
NEUROMODDULATION TREATMENT.
THIS INFORMATION OF POTENTIAL
SUBTYPES COULD ALSO BE USED TO
GUIDE THE DESIGN EVER
PERSONALIZED TREATMENT FOR
EXAMPLE, TO PROMOTE THE
PROTECTIVE CIRCUITS FOR
PARTICIPANTS WITH A HIGHER RISK
OF CIRCUIT BUT WITHOUT THE
BALANCE OF THE PROTECTIVE
CIRCUIT LIKE CLUSTER 5 AT TOP
LEFT CORNER SHOWS.
SO TO SUM UP HERE WE PROMOZ A 2
STAGE TARGET PRESCREENING ANDEM
DIDON STRAIGHTED THE STAGE 1 IN
DETAILS THAT INVOLVES SYSTEMATIC
LOAMACYY COMPREHENSIVELY
EXPLORING ROIs FOR A SPECIFIC
DISEASE, THE INCOME STEP WOULD
BE TESTING THESE POTENTIAL
TACKERETS WITH CLINICAL TRIALS
FOR TARGET ENGAGEMENT AND
TREATMENT ADVOCACY.
EXAMPLES ARE 2 ONGOING CLINICAL
STUDIES HERE AT NIDA, BASED ON
THE INVOLVED MENTION SIMILAR
WORK ON THE HUMAN DLPC, 1 IS A
CONCURRENT STUDY LEAD BY
DR. [INDISCERNIBLE] STUDYING
TARGET ENGAGEMENT AND ACCURATE
EFFECT ON THE DPLC, WITH THE
HEALTHY PARTICIPANTS THE OTHER
IS AN OFFLINING EYE TBS
TREATMENT STUDY BY
DR. [INDISCERNIBLE], STUDYING
TREATMENT EFFICACY OF THE DLFPC
STIMULATION FOR TREATMENT FROM
SEEKING COCAINE USERS.
THIS IS ALL I WOULD LIKE TO
ACKNOWLEDGE MY SUPER VISOR
COLLEAGUES AND COLLABORATE OARS
AND MY INSTITUTE FOR MAKING THIS
STUDY POSSIBLE.
AND LAST BUT NOT LEAST DEPENDING
ON THE SET UP, I MAY OR MAY NOT
BE ABLE TO ANSWER YOUR QUESTIONS
BUT PLEASE FEEL FREE TO REACH
OUT TO ME SHOULD SHOULD YOU HAVE
ANY.
THANKS IF ARE YOUR ATTENTION.
[ APPLAUSE ]
, OKAY, THANK YOU VERY MUCH FOR
ATTENDING THIS SESSION.
WE ARE A LITTLE BIT BEHIND THE
SCHEDULE SO IT WOULD BE NICE IF
YOU CAN BE BACK IN 15 MINUTES TO
START THE NEXT SESSION.
SO LET'S START
WITH THE FIRST SPEAKER,
DR. DESMOND OATHES, FROM THE
UNIVERSITY OF PENNSYLVANIA.
>>THANK YOU FOR STICKING AROUND
AND LISTENING TO ME SHARE MY
WORK AND THE FOR THE INVITATION.
THIS IS A SUBTITLE FOR MY TALKS
TITLED THE ORIGINAL TITLE
BUILDINGA I DISCOVERY PIPELINE
AND HOPEFULLY I HAVE FLESHED OUT
AND PIQUED YOUR INTEREST.
I DON'T HAVE ANY DISCLOSURES, SO
THIS WAS MENTIONED ACTUALLY IN
THE LAST TALK ABOUT THE PATH TO
FINDING NEW TARGETS AND TESTING
THEM AND SLOW AND ARDUOUS AND
TRYING TO FIGURE OUT WAYS OF
SPEEDING UP THAT PROCESS WOULD
BE VERY WORTH WHILE SEE, LIKE
THE TYPICAL OLD STYLE OF DOING
OUR TREATMENT OR DEPRESSION
TAKES QUITE A WHILE, LIKE 4 TO 6
WEEKS, OF DAILY TREATMENT, IT
COSTS A LOT.
THERE'S A BIG BURDEN ON
PROVIDERS AND THE RESEARCHERS,
THE PATIENTS HAVE TO WAIT A
REALLY LONG TIME, NOT CLEAR WHAT
TO DO WITH THEM WHEN THEY DON'T
RESPOND.
WE FIND THAT IT DOES WORK ON
AVERAGE, WE DON'T KNOW WHY
TYPICALLY, YOU DON'T HAVE A
BRAIN RESPONSE OR ANYTHING THAT
YOU MEASURE, ASIDE FROM
SYMPTOMS, YOU JUST KIND OF
FIGURED THAT YOU CHANGED
SOMETHING AND THEN YOU HELP WITH
THE SYMPTOMS AND THAT'S ALL YOU
KNOW.
YOU DON'T KNOW WHY, WHAT PART OF
YOUR PROTOCOL REALLY WAS THE
MOST EFFECTIVE, THE DOSE TIMING,
THE TARGET, THERE'S USUALLY SO
MANY UNKNOWNS THAT COME OUT EVEN
WHEN THE CLINICAL EFFECT GOES.
WHY SHOULD YOU CARE WHY IT
WORKS, IF IT, WOS THEN JUST DO
IT, RIGHT?
BUT IF YOU UNDERSTAND A LITTLE
BIT MORE ABOUT WHY IT WORKS,
THERE'S THE PERSPECTIVE OF
UNDERSTANDING, LEARNING A LITTLE
BIT MORE MENTAL ILLNESS ISSUES
ET CETERA, THAT'S BEEN IN A LOT
OF OUR IMAGING GRANTS FOR MANY
DECADES AND UNFORTUNATELY IT
HASN'T TRANSLATED INTO MUCH OF A
CLINICAL BENEFIT BUT I STILL
THINK UNDERSTANDING IS IMPORTANT
BUT MAYBE MORE DIRECTLY
APPLICABLE AND PRAGMATIC IS TO
FURTHER OPTIMIZE WHAT THEY'RE
DOING AND MAKE THE TARGETS AND
TREATMENT PROTOCOLS EVEN BETTER.
SO YOU GET THESE SITUATIONS
WHERE A SIMULATION PROTOCOL
WORKS FOR SOME PEOPLE AND IT
DOESN'T WORK FOR OTHER PATES.
YOU HAVE A PATIENT THAT COMES IN
DISTRESSED ON THE LEFT SIDE, YOU
APPLY TMS SOMEWHERE, USUALLY
DLPFC AND SOME PEOPLE GET
BETTER, SOME PEOPLE DON'T HAVE
ANY CHANGE, OTHER PEOPLE GET A
LITTLE WORSE.
WE HAVE NO IDEA, WHY, RIGHT?
AND ESPECIALLY FOR THESE POOR
FOLKS WHO ARE NOT RESPONDERS,
YOU PROBABLY HAD 1 MAIN
TREATMENT AND IT DIDN'T WORK FOR
THOSE GUYS AND NOW YOU WASTED A
LOT OF TIME AND YOU DON'T KNOW
WHAT TO DO WITH THE PATIENT.
SO IN MY LAB WE DO A LOT OF
TMS/FMRI, SO WE ISSUE BRAIN
RESPONSES.
ONE OF THE CONVENIENT THINGS
ABOUT THAT IS THE BOLD RESPONSE
IS SLOW SO CAN YOU PING A
CIRCUIT AND YOU CAN CAPTURE THE
DOWN STREAM EFFECTS CAUSED BY
THE STIMULATION THROUGHOUT THE
BRAIN, CAN YOU MEASURE THESE
RESPONSES AND YOU AVERAGE THEM
FOR MANY TRIALS JUST LIKE ANY
OTHER EVENT RELATED FNRI DESIGN
AND YOU CAN SEE WHERE DOES THE
COMMUNICATION GO WHEN YOU
STIMULATE A PARTICULAR CIRCUIT.
AND SO WE'RE VERY INTERESTED IN
MY LAB AND I BE THIS IS
CONSISTENT WITH WHAT A LOT OF
YOU GUYS ARE DOING IN DEVELOPING
A NEUROMODDULATION DISCOVERY
PIPELINE, USING TMS FMRI, MAYBE
WE CAN USE IT IN A WAY THAT WILL
SPEED UP THE PROCESS, TEST
HYPOTHESIS ABOUT BRAIN CIRCUITRY
AND HOW RESPONSIVE IT IS TO
STIMULATION AND MAYBE EVEN IN
SOME WAYS RESCUE NEUROIMAGING
FOR THE USE IN PSYCHIATRY EVEN
WHEN THERE ARE THESE COUNTER
EXAMPLES OUT IN THE LITERATURE
THAT PEOPLE ARE VERY CONCERNED
WITH TRYING TO DETECT
ABNORMALITIES, ET CETERA.
SO THE FIRST THING YOU CAN DO IS
YOU START WITH IN THE PIPELINE
MAKING A NEW TARGET.
THIS IS YOUR HYPOTHESIS, YOU
SAY, HEY, I THINK I HAVE A NEW
CLEVER WAY OF MEASURING BRAIN
AND I WANT TO AND I WANT TO TRY
STIMULATING THAT PATHWAY AND SEE
WHAT IT DOES, AND IT DOESN'T
HAVE TO BE CONFINED TO 1
PARTICULAR KIND OF THEORETICAL
BEND IN WHAT YOU THINK IS THE
BEST WAY TO TARGET, YOU CAN TEST
THEM ALL.
SO IF YOU HAVE 1 BASED ON METE
YORK DISCIPLINARY AM NAICS OR
THEORY, GRAFT THEORY BASED ON
DTI, IN EFIELDS, COMBINE THIS
THEM HOWEVER YOU WANT TO THESE
ARE ALL PROMISING THINGS WE
SHOULD BE TRYING IN VARIOUS
WAYS.
BUT THE NEXT STEP IS A LITTLE
TRICKIER WITH TARGET ENGAGEMENT.
YOU DO A LITTLE RTMS ON A
DEPRESSED PATIENT AND THEY DON'T
SAY THAT FEEL BETTER AND THEY
SAY OW, THAT HURTS, AND YOU SAY
YOU NEED TO COME BACK FOR A LOT
OF SESSIONS BEFORE WE SEE
ANYTHING CONCONVENIENT.
SO IT WOULD BE CONCONVENIENT AND
USEFUL IF YOU CAN SHOW THEM SOME
WAY TO ENGEAJ THEM AS A CIRCUIT
AS A PROOF THAT YOU'RE AIMING
FOR SOMETHING AND TMS CAN
ACTUALLY DO SOMETHING TO THAT
CIRCUIT.
SO IF YOU THROW IN THE TMS FMRI,
YOU CAN STIMULATE THESE
CIRCUITS, MULTIPLE PLACES AND
YOU CAN GET A RESPONSE IN THE
PLACE I WAS TRYING TO GET AN
EVOKED RESPONSE ISSUES YOU GET A
LOT OF MAP OUT SO YOU GET A LOT
OF INFORMATION FOR DOING THIS
AND YOU DO ENGAGEMENTS.
ALL RIGHT SO IN MY LAB WE DO
SOMETHING LIKE THIS.
THESE ARE THE LITTLE BLUE ARE
THE SPECIFIC TRs, AND YOU GET
A RESPONSE FROM AND SO, WE HAD
GAPS, ACTUALLY BETWEEN EACH TR
AND THE NEXT IN WHICH WE APPLY A
SIPPINGLE PULSE TMS, SO IT'S NOT
NEUROMODDULATION, IT'S PROBING,
MAPPING, ENGAGE BEING CIRCUITS.
AND THROUGH THAT WE DEVELOPED
THIS CAUSAL MAP.
STIMULATE HERE WHERE DOES THE
ACTIVITY PROP GATE?
ON THE TIME SCALE OF AN FMRI
RESPONSE, RADIOIT?
AND SO WE'VE BEEN DOING THIS FOR
A VERY LONG TIME AND WE START
WIDE CONONICLE RESTING STATE
NEST WORKS AND HEALTHY CONTROLS
AND WE CAN ENGAGE NETWORKS BY
STIMULATING NOTE NODES ON THE
NETWORK AND USING THE READ OUT
OF FMRI TO TELL YOU THAT YES
INDEED, YOU FOCUSED ON A
SPECIFIC NETWORK, YOU PING IT,
WITH THE SINGLE PULSES AND YOU
CAPTURE AN EVOKED RESPONSE IN
THE BRAIN NETWORK AND SAY, OKAY,
WE'RE ON TO SOMETHING, I THINK
WITH THIS PROBING ENGAGEMENT
STUFF, LET'S KEEP GOING WITH IT.
SO I DID THIS WITH USING RESTING
FMRI TO PERSONALIZE TARGETING OF
TMS, SO COLLECT A BASE LINE
SESSION, RESTING FMRI, BASIC
BASE CONNECKATIVITY, LOOK FOR
HOT SPOTS ON THE SURFACE OF THE
BRAIN, STIMULATE THEM FOR AN
AMIC DUALA TARGET AND A SINGULAR
TARGET RELATIVE TO ANXIOUS AND
DEPRESSION AND SAY, WHEN CAN CAN
WE ENGAGE THESE CIRCUITS?
LET'S TRY THESE CIRCUITS.
THEY'RE REMOTE PRESIDENT
CIRCUITS OF BRAIN AND IF WE CAN
ENGAGE THEM, THEY WOULD BE
USEFUL AND THEY'RE INTERESTING
FOR WHAT TARGET YOU ARE CHASING
AND WHAT BRAIN REGION YOU'RE
STIMULATING SO THERE WAS
DISCUSSION EARLIER ABOUT AMIG
DUALA TIEWLA PATHWAYS, DIRECT,
INDIRECT, THIS IS A WAY OF
SHOWING THAT ENGAGING THE
CIRCUIT CAN BE DONE IF IT'S
INTERACTING AND IN OUR INITIAL
FORAY INTO THESE CIRCUITS WE
FOUND THAT LOOKING AT FUNCTIONAL
PEAKS THIS FOR MATTER, IT DIDN'T
MATTER WHAT YOU WERE STIMMULING
AS LONG AS IT'S A HIGH
CONNECTING.
SO THE AMYGDALA IT SEEMED TO
MACK A DIFFERENCE IN THE EVOKED
RESPONSE.
SO THE DLCP, THEY TENDED TO SHOW
A POSITIVE EVOKED RESPONSE
WHEREAS MOTOR CORTEX AND DLPFC
HAD A NEGATIVE INVOKED RESPONSE
WHICH WE ARE THINKING MAYBE THE
DIRECTION THAT WE WANT SO THE
SINGULATE WE REPLICATED A MUCH
LARGER SAMPLE AND SHOWED WE GET
CONSISTENT EVOKED RESPONSES IN
THE NEGATIVE DIRECTION WHICH IS
DIFFERENT ACTUALLY THAN THE
PAPER THAT WAS MENTIONED EARLIER
FROM BRUCE AND HOLLY, THEY'RE
SHOWING A POSITIVE EVOKED
RESPONSE SO IT'S NICE THAT
THERE'S ACTUALLY DIFFERENT
CIRCUITS THAT CAN BE--THAT CAN
ENGAGE THE DOWN STREAM BRAIN
AREA, DIFFERENTIALLY EMPLOY SO
WE DID OUR SIMILAR DESIGN PAIR
WITH THE INTERLEAVE AND IT ALSO
MATTERED SO THIS IS A MUCH
BIGGER SAMPLE, 78 HEALTHY
CONTROL ASKS WHEN WE ELECTRIC AT
ANTICORRELATED LIKE THE POPULAR
1, VERSUS POSITIVATIVELY
CORRELATED SPOTS AND HEALTHY
CONTROLS, BOTH OF THEM DID
PRETTY WELL.
THEY ENGAGED THE CIRCUIT AND
SHOWED A NEGATIVE EVOKED
RESPONSE BUT ACTUALLY IN THE
PATIENT, SOMETHING DIFFERENT
HAPPENED, THE ANTICORRELATED DID
ENGAGE THE CIRCUIT, BUT THE
POSITIVELY CORRELATED SPOTS
ACTUALLY ENGAGED IT BETTER.
SO IF WHAT WE'RE REALLY TRYING
TO DO IS ENGAGE WITH THAT
CIRCUIT AND IT'S MECHANISTICALLY
IMPORTANT FOR DEPRESSION
TREATMENT, WE MIGHT TRY THE
POSITIVELY CORRELATED SPOTS IF
THAT'S REALLY--IF WE'RE REALLY
UNDERSTANDING THE MECHANISM
WE'RE AIMING FOR.
ALSO THERE WAS DISCUSSION OF
AMYGDALA EVOKED RESPONSE SO I
SHOW THAT SMALL STUDY INITIALLY
AND WE ACTUALLY REPLICATED THAT
EFFECT IN A MUCH LARGER COHORT,
AND SHOWED A CONSISTENT ARK MIG
DUALA DUALA EVOKED RESPONSE
THROUGH VLPC PATHWAYS, SO VPLC,
AND SO WAS COMPLETELY CONSISTENT
WITH OUR SMALLER PILOT STUDY, WE
ALSO DID DTI AT BASE LINE AND
LOOKED TO SEE IF WE DID
[INDISCERNIBLE] THROUGH PUTATIVE
PATHWAY, CONNECTING THE VLPFC TO
THE AMYGDALA NETWORK AND FOUND
THERE IS AN ASSOCIATION BETWEEN
THE AMYGDALA EVOKED RESPONSE AND
FIBER DENSITY IN THAT AMYGDALA
PATHWAY SO WE KNOW TMS LIKES TO
FOLLOW WHITE PARTY PATHWAYS,
THIS IS KIND OF REASONABLE BUT
AGAIN MORE SUPPORT FOR THE
EVOKED RESPONSES TELLING US
SOMETHING INTERESTING ABOUT THE
CIRCUIT.
BACK TO THIS PIPELINE.
WE SHOWED EVIDENCE OF MAKING A
TARGET, ENGAGING THE TARGET,
THOSE THINGS SEEM TO BE WORKING,
NEXT WE WANT TO SEE, OKAY, WELL,
ENGAGING CIRCUITS THAT'S
INTERESTING BUT IS IT AT ALL
RELEVANT TO ACTUALLY BEHAVIORIAL
CHANGES YOU WOULD SEE WITH
REPETITIVE TMS, SO WE DESIGN
THIS AND CAPTURE AND SPEED UP
THE PROCESS OF TESTING CIRCUITS
AND THE MODULATION, TRYING TO
SAY WHAT IS KIND OF THE MINIMAL
DOSE WHERE WE PRETTY
CONSISTENTLY IN THE LITERATURE
SEE RTMS INDUCED DEPRESSION
CHANGES.
SO IT'S SOMEWHERE AROUND THIS
TIME PERIOD OF
TROUGH--TROJANOWSKIITATIONAL
PROTOCOL AFTER A COUPLE WEEKS
AND SEWE SAID, OKAY, WE'LL MAKE
THIS DOSE ABOUT THAT BIG AND WE
THINK WE WILL MOVE DEPRESSION
AND WE'LL LOOK AT THE BRAIN
RESPONSES TO TMS FMRI AND SEE IF
THERE'S RELEVANCE THERE, AGAIN
NOT TRYING TO MOVE THAT THIS IS
TRYING TO QUICKLY ITERATE
THROUGH SHORT DIRECTION KIND OF
SMALL INTERVENTIONS WE THINK ARE
ENOUGH TO MOVE SYMPTOMS, MOVE
THE CIRCUIT AND DEMONSTRATE THE
RELEVANCE OF TMS THERE.
SO NEXT WE WANT TO MAKERS AND
SURE WE MODULATE THE
TARGETTINGLY SENGULATE RELATED
TMS FMRI AND MAPPING BEFORE HAND
AND THEN WE HAVE THIS 3 DAY
MINIINTERVENTION AND THEN DO THE
PING OF THE CIRCUIT AGAIN AND
SEE WHAT CHANGED.
THIS IS OUR SCAN PROTOCOL SO WE
WERE DOING A BASE LINE TO
DETERMINE THE CONNECTIVITY
TARGETS BUT THEN WHEN WE DO THE
TMS FMRI SESSION WE DID THE
PROBE INTERLEAVE AND AROUND,
SHORT ROUND OF DATA BURST IN THE
SCANNER.
WHEN THEY'RE OUTSIDE OF THE
SCANNER GETTING OUR INTERVENTION
THEY COME BACK FOR 3 DAYS, THEY
GET 2400 PULSE TRIPLETS OF ITBS
THROUGH THEIR [INDISCERNIBLE]
PATHWAY, AND INDEED WE FOUND
THERE WAS A CHANGE IN THE VERSUS
POST TMIs AND WE GOT SOMETHING
STRONGER IN RESPONSE TO THE
DEMONSTRATION.
SOPHISTICATEDY WE DEMONSTRATED
TARGET, ENGAGEMENT MODULATION,
SO FAR SO GOOD.
WHAT YOU REALLY WANT KNOW IS
WHAT THAT RELEVANT TO THEIR
SYMPTOM CHANGES, FERS IT RELATED
DID ANYTHING HAPPEN TO THE
CIRCUIT THAT SHOWS THE
ASSOCIATION.
WE REALLY WANT THAT TO HAPPEN
PROBABLY WOULDN'T BE STANDING
HERE TALKING ABOUT THE WORK BUT
THIS IS THE PING OF THE CIRCUIT
BEFORE IT, SO YOU SAY ALL RIGHT,
IS A MEASURE OF THE CIRCUMSTANCE
UTR'S INTEGRITY THE EVOKED
RESPONSE DOWN STREAM ACTUALLY
TELL YOU ANYTHING ABOUT HOW WELL
THE INTERVENTION THROUGH THAT
SAME PATHWAY WILL WORK AND IT
LOOKS LIKE IT DID SO IF YOU HAVE
A STRONGER ESCROAKED RESPONSE IN
YOUR SUBGENERATEDDULE TO THAT
PLACE WHERE WE WILL DO THE
INTERVENTION, YOU WILL
EXPERIENCE MORE BENEFIT, FROM
THE INTERVENTION THROUGH THAT
SAME PATHWAY.
ALL RIGHT, SO, WE ALSO FOUND--SO
WE FOUND THIS TARGET ENGAGEMENT,
RIGHT.
IT'S RELATED TO SYMPTOM CHANGE.
TMS, FMRI TELLS YOU SOMETHING.
THAT'S GREAT.
ANOTHER PIECE IS THAT--SORRY
HPV-YOU MAY ALSO WANT TO KNOW
WELL WHAT DID THE PING LOOK LIKE
DIFFERENT, DIFFERENTLY FROM THE
PRETO POST INTERVENTION.
SO THERE'S A CHARGE IN THE
CIRCUIT ON AVERAGE IT BECOMES
NEGATIVE, BUT ACTUALLY TO THE
DEGREE THAT IT SHIFTS IN THE
OTHER DIRECTION, TOWARDS
POSITIVE DIRECTION IT SHOWS AN
ASSOCIATION WITH BETTER RESPONSE
TO THE INTERVENTION.
SO YOU SAY, AH, THAT'S REALLY
INTERESTING, CAN WE THROW A
DIFFERENT KIND OF RTMS PROTOCOL
AT THEM.
TO RELIABLE PUSH THAT IN THE
OTHER DIRECTION, IT HOPES UP A
BUNCH OF NEW THINGS TO
POTENTIALLY TEST.
BUT WE'RE ESTABLISHING LONG
ALONG THE WAY LIKE THIS PIPELINE
ENGAGING THE TARGET, MAKING YOUR
TARGET, MODULATING IT, SHOWING
IT WITH ASSOCIATION OF SYMPTOMS,
KIND OF BRINGING EVERYTHING ALL
TOGETHER BUT SINCE WE COLLECTED
THIS RICH DATA SO, THERE ARE
MORE TECHNOLOGY TRANSFERS WE CAN
LOOK AT SO STIMULATING MULTIPLE
PATHWAYS HOW IMPORTANT IS THAT
PATHWAY, THE EVOKED RESPONSE
THROUGH THIS SPOT VERSUS ANOTHER
LIKE ACTIVE CONTROL SITE.
DOES IT MATTER, THAT THIS IS THE
SAME SAME 1 YOU DID THE
INTERVENTION ON VERSUS THE
EVOKED RESPONSE IN THE DOWN
STREAM AREA BUT THROUGH THE
PATHWAY WE DIDN'T APPLY THE
INTERVENTION TO.
SO WE LOOKED AT THAT AND FOUND
THAT OHM THROUGH THE PATHWAY
THAT WE STIMULATED, THERE'S A
RELIABLE ASSOCIATION WITH
DEPRESSION CHANGE AND THAT IT'S
SPECIFIC TO DEPRESSION AND NOT
TO ANXIETY ON THE DES21.
SO WE ARE INTRIGUED BY THIS,
MAYBE THIS IS HIGHLY RELEVANT TO
DEPRESSION, MAYBE LESS REEL
KEEPSAKES VABT TO ANXIETY AND
THERE'S ALSO THE FC STORY THAT'S
OUT THERE, RIGHT WITH THE
ANTICORRELATION AND WHAT WE
FOUND IS ACTUALLY THE BASE LINE
SESSION WE COLLECTED ON AVERAGE
10 DAYS BEFORE THE INTERVENTION
STARTED WAS NOT A PREDICTOR OF
HOW WELL PEOPLE ARE GOING TO
RESPOND TO THE STIMULATION
PROVIDED.
BUT IF YOU COLLECT FC CLOSER TO
IN TIME TO THE INTERVENTION WE
DID ISSUES ISSUES THIS WAS A
PREDICTOR AND NOT ASSOCIATION OF
THE LITERATURE ISSUES THE IN THE
POSITIVELY CORRELATED SPOT, THE
STRONGER THE POSITIVE
CORRELATION, THE BETTER THE
PATIENTS RESPONDED TO TREATMENT
SO IT THROWS UP A WHOLE BUNCH OF
NEW THINGS, A LITTLE LIKE--A
LITTLE ROCK IN THE RENCH OF
GEARS OF SAYING, OKAY BEING WE
HAVE IT ALL FIGURED OUT NOW WHAT
THE BEST PATHWAY IS, AND
RETREATING PATIENTS, MAYBE NOT,
BUT LEARNING FROM IMAGING AND
THERE'S MORE DATA SO AS I
MENTIONED WE COLLECT THE WHOLE
BRAIN DATA AND WE WANT TO KNOW
IS THERE ANYTHING ELSE
INTERESTING IN THERE AND HERE'S
ANOTHER PIECE OF THE EXTRAS THAT
COULD FEED THE NEXT PLANNED
TARGET.
AND SO WE LOOK AT WHAT OTHER
AREA IN THE BRAIN DO WE SEE THE
CHANGE FROM THE EVOKED RESPONSE
FROM PRE TO POST THAT ARE
ASSOCIATE WIDE SYMPTOM
IMPROVEMENT AND THE THIS POPPED
UP AS A WITHIN THE WHOLE BRAIN
KIND OF APPROACH AS A PLACE THAT
RESPONDED WELL ASSOCIATED WITH
THE OUTCOME BUT THERE ARE A
BUNCH OF OTHER SPOTS, TOO,
PERIHIPPO CHAMPAL GYRUS AND
POSTERIOR SINGULATE, AND ANXIETY
DID IMPROVE THROUGH THE CIRCUIT
IT WAS JUST NOT RELATED TO THE
GENERAL EVOKED RESPONSE.
WHAT ARE THE PLACES THAT ANXIETY
IS SOCKED WITH CHANGE IN
COMMUNICATION THROUGH THE
CIRCUIT.
AND THERE ARE AREAS, SO THERE'S
A NEARBY REGION AT THE MPSC, THE
1 IN THE AMYGDALA SUGGESTING
THAT MAYBE FUNCTIONAL
CONNECTIVITY THORS THOSE IF THEY
CANNOT RESPOND TO ANXIETY OR
ANXIETY IS THE PRIMARY SYMPTOM
YOU WILL TRY TO SHOOT FOR.
SO THAT'S PART OF FEEDING THE
NEXT PIPELINE AND THE EVOKED
RESPONSE WITH IMAGING MODALITY
IT'S A RESPONSE TO TMS, DIRECT
RESPONSE TO TMS, SO YOU SAY,
OKAY IF YOU WANT TO ENGAGE A
CIRCUIT WITH TMS, YOU CAN DO
THIS TMS FMRI IT'S ESPECIALLY
RELEVANT TO WHETHER THE
NEUROMODDULATION PROTOCOL
THROUGH THAT CIRCUIT WILL BE
THERE.
OTHER THINGS WE CAN DO
POTENTIALLY, IN THE FUTURE IS
WHAT IF YOU MULTIPLE THEORIES
ABOUT HOW TO PROPERLY TARGET A
SPECIFIC PATHWAY.
I WILL USE THIS ATLAS, I WILL
USE THIS PARTIAL SCHEME, I WILL
USE DTI, I WILL USE MULTIECHO
RESTING STATE, WHATEVER YOU
WANT, RIGHT?
YOU CAN GENERATE MULTIPLE
TARGETS FROM ANY BISE LINE
SESSION YOU WANT AND YOU CAN
PING EACH 1 OF THOSE AND SAY,
WHAT I CARE ABOUT IS THE CANNED
WHAT OR AMYGDALA OR THE NETWORK
AND YOU CAN PING IT IN THE
SCANNER, PING MULTIPLE SPOTS AND
SAY WHEN 1 OF THESE ACTUALLY
GIVES YOU THE BEST INVOKED
RESPONSE IN THAT NETWORK OR
REGION OF INTEREST FOR THAT
PATIENT THROUGH THAT TARGET.
AND WE THINK BASED ON THIS
ACCUMULATING EVIDENCE, RIGHT?
THAT YOU CAN USE THAT CLINICALLY
TO SAY, FOR THIS PATIENT SHOULD
BE HERE, FOR THIS PATIENT IT
SHOULD BE THERE.
AND HOPEFULLY WE WILL SPEED UP
THE RESPONSIVENESS TO TREATMENT
AND LEAD TO NEW CONSTANT
TARGETS.
SO QUESTION IS, ARE WE MAKING
PROGRESS THEN KNOWING WHAT IN
THE WORLD IS HAPPENING IN
RESPONSE TO TMS WHEN WE APPLY IT
TO VARIOUS PLACES ON THE SCALP
AND NOT KNOWING EXACTLY WHAT'S
HAPPENING UNDERNEATH?
WE THINK THAT HOPEFULLY, WE ARE
START NOTHING THAT DIRECTION.
AND CONSISTENT WITH THIS
PIPELINE, WE MADE A TARGET, 2
DIFFERENT TARGETS, THEY SEEM TO
ENGAGE THE CIRCUIT, WE
DEMONSTRATED THE ENGAGEMENT OF
THE CIRCUIT WITH THE SINGLE
PULSES.
WE DID A BRIEF INTERVENTION
PROTOCOL TO SHOW WE CAN MODULATE
THESE THINGS, WE SAW A CHANGE IN
THEM, SIGNIFICANT CHANGE AND WE
BUILT THE ASSOCIATION BETWEEN
THOSE PINGS TO MEASURES BEFORE
THE TREATMENT, AND IN RESPONSE
TO THE INTERVENTION RELATED TO
THE SYMPTOM CHANGE AND THEN
THROWING IN EXTRAS, WE'RE NOT
DONE INTEGGIC--STRATEGICIGATING
THE DATA SET, THERE ARE OTHER
THINGS WE CAN EXPLORE.
SO SO IN THE FUTURE, I MENTION
THIS BEFORE, BUT YOU CAN USE
OTHER IMAGING MODALITIES, OTHER
APPROACHES TO DECIDE WHAT THE
BEST TARGET IS AND TEST THEM.
ALSO OF COURSE, WE WANT TO TAKE
THE MOST PROMISING 1S AND MOVE
THEM INTO A LONGER OR HIGHER
DOSE STIMULATION PROTOCOL AND
SAY, ARE THESE STILL LIKE THE
MOST EFFECTIVE THINGS WE CAN BE
DOING, SHAM CONTROL, THIS IS
PART OF THE PROCESS OF REALLY
LAUNCHING A NEW--MAKING A CLAIM
THAT YOU HAVE A NEW TREATMENT
TARGET, RIGHT?
THAT'S ESSENTIAL WORK.
THE PIPELINE GETS YOU THERE, BUT
THEN YOU REALLY HAVE TO VALIDATE
THAT THIS IS, YOU KNOW COULD BE
BE SHAM AND THERE'S OTHER WORK
IN MY LAB WHERE WE'RE TRYING TO
UNDERSTAND BETTER THE TMS
REVOKED RESPONSE, HOW TO OOH
QUIRE THE DATA BETTER AND
ANALYZE IT BETTER AND I HAVE A
WONDERFUL TEAM OF COLLABORATORS
AND FOLKS IN THE LAB FUNDING
AGENCIES HAVE BEEN VERY GENEROUS
TO US, ESPECIALLY AT NIH.
AND AND THANK YOU FOR YOUR
ATTENTION.
I HAD A QUESTION, SO THE DATA
YOU ARE SHOWING IS DIFFERENT
THAN THE OTHER CORRELATION, SO I
TEND TO BELIEVE ALL DATA
AGNOSTICALLY THAT I'M NOT SAYING
1 IS WRITE OR WRONG BUT WHAT
MAKES THE DIFFERENCE?
THE OTHERS THAT ARE FINDING
ANTICORRELATION, WHERE ARE THEY
FINDING THE OPPOSITE AND SOME OF
THE THINGS I'VE THOUGHT ABOUT IN
TERMS OF VARIABILITY AND DATA
AND/OR DATA ANALYSIS MIGHT HAVE
TO DO WITH HOW DATA IS BEING
PROCESSED.
YOU KNOW I KNOW THERE'S THIS
GLOBAL REGRESSION DEBATE AND
WHETHER IT WANTS YOU TO TAKE
THAT OUT OR NOT, AND ALSO
DIFFERENCES RELATED TO AGE,
RELATED TO SYMPTOM PRESENTATION.
YOU KNOW MAYBE IT'S BEST
FOR--THIS 1 IS GOOD FOR
ANADONNIC DEPRESSION, THIS IS
BEST FOR SOME OTHER FORM OR
FLAVOR AND SO, I GUESS JUST YOUR
THOUGHTS IN TERMS OF WHAT IS
DRIVING THE DIFFERENCES AND THE
FINDINGS AND I GUESS, MY THOUGHT
IS IT'S PERHAPS BOTH BUT FOR
DIFFERENT PEOPLE OR DIFFERENT
WAYS YOU ANALYZE IT OR I DON'T
KNOW WHAT'S YOUR THOUGHT ON
THAT?
>>EXACTLY THE SAME QUESTION.
I FOUND YOUR BRAIN BEHAVIOR
CORRELATION TO BE THE MOST
IMPRESSIVE.
MY QUESTION--LET ME KEEP IT
SHORT.
SUPPOSE YOU CHANGE THE FMRI
REPROCESSING PIPELINE, RIGHT, DO
A DIFFERENT SET OF PARAMETERS,
DOES THAT CORRELATION CHANGE.
HAVE YOU LOOKED INTO HA?
>>I HAVE ONLY PLAYED AROUND
WITH GLOBAL WITH THE RESPONSE
STAYING CONSISTENT.
SO AS TO THE BROADER KEOF WHY
DOEUR DATA LOOK LOOK THEY MIGHT
BE INCONSISTENT, THERE ARE A LOT
OF ANSWERS TO THAT.
ONE EVER THEM, I THINK THE
EASIEST 1 IS TO SAY THAT OTHER
FOLKS HAVEN'T LOOKED WIDELY
ENOUGH WITHIN FC, IF YOU SEE THE
RANGES WHEN THERE'S ASSOCIATION
WITH OUTCOME BETWEEN THE
ANTICORRELATION AND THE OUTCOME,
THEY'RE USUALLY VERY LIMITED ON
THE SIDE OF POSITIVE
CONNECTIVITY.
I THINK IT HASN'T BEEN EXAMINED
CLOSELY ENOUGH.
I WILL ALSO SAY THAT IN OUR DATA
IT DIDN'T LOOK LIKE THE
ANTICORRELATED SPOT DIDN'T
ENGAGE THE SUBGENERATEDDULE, IT
LOOKED LIKE IN PATIENTS WHO ARE
UNMEDICATED IN MY CASE, ANOTHER
VARIABLE, RIGHT, THE POSITIVELY
CORRELATED SPOT JUST BETTER AT
ENGAGING THE SUBGANNAULE, SO IF
YOU DID A TREATMENT THROUGH THE
ANTICORRELATED SPOT, MAYBE IT
WOULD WORK IF WE ASSUME THAT
SUBGRANNULES IS WHAT YOU'RE
AFTER BUT MAYBE IT WOULD BE
FASTER AND BESTER IF YOU WENT
THROUGH POSITIVE LOW CORRELATED
SPOTS SO WHAT HAPPENS IF YOU GO
OVER A INTENSIVE PROTOCOL
THROUGH MANY, MANY SESSIONS THAT
PERHAPS WEEKER ENGAGED
ANTICORRELATED TARGET.
IT MAY BE THE CLINICAL EFFECT IS
STILL PRETTY ROBUST TO THAT EVEN
THOUGH IT'S A BIT WEEKER BUT
MAYBE LIKE IT COULD BE FASTER OR
MORE ROBUST OR LAST LONGER IF WE
ABOUT THROUGH THE POSITIVELY
CORRELATED SPOT.
WE DON'T KNOW.
WE JUST INVITE ALL OF THOSE
SUGGESTIONS AS TO PEOPLE'S IDEAS
AND I THINK WORTH PURSUING THEM,
I'M HOPING TO SHIFT PEOPLE'S
CONSCIOUSNESS OFF OF THE IDEA
THAT WE HAVE IT FIGURED OUT,
THAT THE CORRELATED SPOT IS IT,
THEREFORE DONE, WE KNOW HOW TO
FIX IT, JUST INVITE MORE KIND OF
FOLKS TRYING OUT OTHER TYPES.
>>SORRY, JUST IT FOLLOW UP ON
THAT HOW FAR AWAY IN BRAIN
GEOGRAPHY IS THE ANTICORRELATED
TO THE POSITIVELY CORRELATED ARE
WE TALKING ABOUT A PRETTY DARN
CLOSE SPOT THAT IF YOU WITH A
NORMAL COIL, SOMEONE NOT SUPER
PRECISE THAT YOU WOULD HIT BOTH
OR EITHER OR EITHER OR HOW FAR
AWAY ARE THESE SPOTS FROM EACH
OTHER TYPICALLY.
>>SO THE WAY WE TARGET OUR SPOT
SYSTEM TO FIND HIGHLY HOMOGENOUS
REGIONS FOR AT LEFT A COUPLE
CENTIMETERS IN ALL DIRECTIONS
THERE'S ALSO NOT A HIGH NEGATIVE
PEAK BECAUSE WE'RE TRYING TO
SUPPORT THE IDEA THAT THE
POSITIVE PEOPLE WORK BUT IF YOU
LOOK JUST ON MMNI SPACE ACROSS
ALL THE PLACES WE STIMULATE THEY
DON'T LOOK VERY DIFFERENT FROM
THE ANTICORRELATED SPOT FIST YOU
DO THE SAME THING BUT AT THE
INDIVIDUAL SUBJECT LEVEL, RIGHT,
THERE ARE THESE BEAUTIFUL
ISLANDS OF POSITIVE CORRELATION
THAT ARE ROBUSTLY THERE IN
DLPFCKISH TERRITORY FOR EVERY
PATIENT WE LOOKED AT, EVERY
HEALTHY SUBSCRECT WE LOOKED AT.
THEY'RE CONSISTENTLY THERE.
IF YOU ELECTRIC AT THE AVERAGE
THEY WASH OUT OF IT AND THERE'S
NOT MUCH GOING ON OZATIVELY BUT
AT THE INDIVIDUAL LEVEL, THEY'RE
VERY, VERY CLEANLY THERE, AND
EVERYBODY THAT WE'VE LOOKED AT
SO FAR.
>>OKAY, THANK YOU.
[ APPLAUSE ]
>>SO THE NEXT SPEAKER IS ANDY
HORN FROM HARVARD.
MANY OF YOU COURSE KNOW THESE
VIDEOS CAN BE HIGHLY EFKEASHES
IN SOME PATIENTS WE ALL KNOW
THAT.
IN THIS PATIENT FOR EXAMPLE IT
IS WITHOUT [INDISCERNIBLE], WE
SEE MARKED DIFFERENCE BETWEEN
SAME TIME, SAME DAY STIMULATION
VERSUS OFF VERSUS OFF ON THE AND
OFF ON THE LEFT AND ON ON THE
RIGHT, BUT AS MANY YOU KNOW THE
TREATMENT OUTCOME IS NOT ALWAYS
AS OPTIMAL.
ONE KEY QUESTION IS TARGETING
AND WE I THINK BY NOW ALL AGREE
THAT OPTIMAL BRAIN CIRCUITS NEED
TO BE MODULATED BY DEEP BRAIN
STIMULATION.
SO FIRST OF ALL THE QUESTION IS
WHICH ARE THE OPTIMAL BRAIN
CIRCUITS AND HOW TO BEST TARGET
AND ENGAGE THEM.
THE SAME APPLIES TO TRANSCRANIAL
MAGNETIC STIMULATION AS WELL SO
AGAIN WE ARE LOOKING AT DEFINING
OPTIMAL BRAIN CIRCUITS AND THEN
USING TMS TO TREAT THEM.
SO THE QUESTION IS HOW DO WE
DEFINE THESE CIRCUITS, RIGHT?
OF COURSE THERE ARE ANIMAL
MODELS WITH THE TRANSLATIONAL
VALUE MODEL REMAINS UNCLEAR AND
THEN OF COURSE FUNCTIONAL MRI OR
FUNCTIONAL IMAGING, WE COULD
LACK AT PASHTS AND COMPARED FOR
EXAMPLE, PATIENTS OR TASKS
VERSUS HEALTHY CONTROLS AND
TASKS AND WE SEE NETWORKS BUT
THE QUESTION IS ALWAYS A
THERAPEUTIC NETWORK WE'RE SEEING
OR COMPENSATORY NETWORK AND THE
SAM WITH ELECTROPHYSIOLOGY, THE
QUESTION WILL REMAIN IS IT
CAUSAL TO TREATMENT?
SO AT THE CENTER OF BRAIN
CIRCUIT THERAPEUTICS WHEN
WORKING RIGHT NOW IN BOSTON, WE
CAME UP WITH A DIFFERENT
TECHNIQUE TO REVERSE THE
QUESTION AND WE ALSO USE BRAIN
LESIONS TO INFORM THE OPTIMAL
BRAIN SUCKER UTR SO WE WANT TO
USE THESE CAUSAL INTERVENTIONS
TO THE BRAIN TO DEFEIGN THE
OPTIMAL BRAIN CIRCUITS AND THEN
THE DEEP BRAIN STIMULATION, THE
QUESTION IS SIMPLE WHICH
CONNECTION IS OPTIMAL, WHICH
TARGET DO WE NEED TO STIMULATE.
WE CAN LOOK AT THAT BY USING THE
VARIANTS IN THREEMENT AND IN
ELECTROPLACEMENT AND LOOKING AT
WHICH CIRCUITS WERE ENGAGED BY
THE PATIENTS THAT DID REALLY
WELL VERSUS THE 1S THAT DID NOT
DO REALLY WELL.
WE'VE DONE THIS IN MANY
INDICATIONS BY NOW, AND I WANT
TO TALK ABOUT THIS FOR OCD,
BECAUSE START WITH THIS SLIDE
BECAUSE THIS IS AN ONGOING
PROJECT IN MY LAB WHERE WE LOOK
AT DBS IN 4 DIFFERENT DISEASES
THAT INVOLVES A LOT OF
COLLABORATIONS WITH A LOT OF
CENTERS.
WHERE WE LOOK AT WHICH TRACTS
WERE IN EACH OF THESE DISEASES,
ASSOCIATED WITH OPTIMAL
RESPONSE, AS YOU KNOW THE
SUBTHALAMIC SKULL KUS HAS A
BROAD AREA AREA IN THE FRONTAL
CORTEX SO WE SEE HERE THAT IN
OCD, THERE'S MORE A TRACT THAT
SEEMS CRITICAL VERSUS IN
DYSTONIA WITH MORE SENSORY AND
SENSORY MOTOR TRACK FOR DREADS
DISEASE AND PARKINSON'S DISEASE.
SO AS I MENTIONED, I WANT TO
FOCUS ON THIS SPECIFIC TRACT
HERE WE FIRST DISCOVERED IN 2019
WORK BY [INDISCERNIBLE], THIS
WAS TAKEN UP BY NING FEI, LI IN
MY TRACK, SO THE KEY THING IS
THAT ALL OF YOU KNOW IS WE HAVE
MULTIPLE TARGETS TO MULTIPLE
TARGETS THAT SEEM TO BE
PROMISING INCLUDING THE BCBS
REGION, SO THE VENTRAL CAPSULE
TRIAT UMKC, WHICH HAS DIFFERENT
TARGETS INCLUDED LIKE THE DID
YOU KUS CUM BENS PROPER, THE
VENTRAL [INDISCERNIBLE].
AND THEN WE HAVE THE REACH AND
THE 4 BRAIN BUNDLE TARGET IS
CLOSE BY.
SO WE WERE SUPER FORTUNATE TO BE
COLLABORATING WITH
[INDISCERNIBLE] LED BY
[INDISCERNIBLE] AND SPEARHEADED
BI CAD
BI--BY [INDISCERNIBLE], AND
THENLESS ALSO SPEARHEADED BY
MIRCEA POLOSAN, AND ASTROORK
D KIBLEUR, AND IF YOU ELECTRIC
AT THE SCIENCE SHOWN IN GREEN,
WE GET DIFFERENT RESULTS RIGHT
SO THE STN AS YOU'VE SEEN BEFORE
OF COURSE CONNECTED TO A LOT OF
FRONT CORTEX IS OF COURSE THIS
IS A DIFFERENT CONNECTIVITY AS
WELL BUT WE IF USE STATISTICS
AND USE THESE BUNDLES WE SEE BY
THEIR ABILITY TO ABILITY
DISCRIMINATE OPTIMAL RESPONDING
PATIENTS AND NONOPTIMAL
RESPONDING PATIENTS WE FIND A
SIMILAR TRACT IN BOTH OF THESE
TARGETS, RIGHT?
SO YOU SEE HERE THAT THE STAIM
TRACT JUST CALCULATED ON THE
PEASHS EMERGES AS THE 1
CALCULATED FROM THE STN PATIENTS
THAT I'VE SHOWN YOU ALSO BEFORE.
SO WE WERE SUPER EXCITED BY THIS
BECAUSE THAT WAS THE FIRST TIME
WE COULD LINK DIFFERENT SURGICAL
TARGETS FOR THE SAME INDICATION
TO A COMMON TRACT TARGET.
AND WE THOUGHT, OKAY, CAN WE NOW
CLALCULATE THIS TRACT ON THE
ALICK PATIENTS AND OVERLAY THE
STN OF THE COHORT, SOME OF THESE
STIMULATIONS WOULD REACH THE
TRACT MORE STRONGLY, OTHERS
WOULD MISS THE AND WE USE THAT
TO CROSS ESTIMATE SO TO ESTIMATE
THE OUTCOMES, AGAIN THAT WAS
CALCULATED ONLY ON THE COHORT
AND THEN THE AIM WAS TO PREDICT
THE OUTCOMES OR THE RANKS OF THE
OUTCOMES IN THE STN PATIENTS SO
YOU SEE THESE 2 EXAMPLES HERE,
DID NOT REACH THE TRACT MATCH,
HAD A LOW FIBER SCORE WE CALL IT
AND THEN THIS HAD A VERY HIGH
FIBER SCORE, YOU KNOW HIT THE
TRACK QUITE RECISELY.
AND THAT CORRELATED WITH
CLINICAL IMPROVEMENT YOU CAN
ALSO DO IT THE OTHER WAY AROUND.
THIS TIME WE ONLY CALCULATE
BASED ON STN WE SEE
NONESSENTIALICAL CLAYINGS HERE
THAT ARE NOT IMPORTANT AND WE
OVERLAY THE COHORTS AND SOME HIT
THE TRACK AND MISS THE TRACK,
SAME THING HERE, THIS FEATURE
COMPLETELY MISSED THE TRACT, HAD
A POOR RESPONSE, THIS DID
PARTIALLY CAPTURE THE TRACT AND
HAS ADEQUATE GOOD RESPONSE.
LOOKING AT OTHER INDICATIONS
FROM THE LITERATURE, YOU SEE
THAT THESE SEEM AROUND THE TRACT
SO THESE TARPGETS STICK UP
THAT'S WHY THEY ARE A BIT MORE
VENTRAL TO THIS AND WE COULD
EVEN CALCULATE THE DISTANCE
BETWEEN THE TARGET SIDES WITH
THE TRACT AND CORRELATE THAT
WITH THE REPORTED AVERAGE
OUTCOME IN EACH OF THESE STUDIES
SHOWING THAT AGAIN, THIS WAS A
CLEAR RELATIONSHIP, THE CLOSER
YOU WERE, THE TARGET WAS TO THAT
TRACT, THE BETTER THE OWM COME
AND THE STUDY.
SO WE PRESENTED THIS WORK AT
CONFERENCES AND WE'RE QUITE
FORTUNATE THAT THE T-FROM LONDON
AND THE TEAM FROM MADRID PITCHED
IN TO ADD ADDITIONAL DATA TO
THIS, TO VALIDATE IT FURTHER
SOPHISTICATEDY WE ADD 2 MORE
CORHOTTERS, THIS TIME CALCULATE
THE TRACT BASED ON THE FIRST 2
COHORTS AND THE SAME THING
EMERGES NOW A BIT MORE CRYSTAL
CLEAR, A PRECISE AND WE AGAIN
NOW OVERLAY THE SIMULATION
VOLUMES FROM THE OTHER 2 COHORTS
AND THE MORE THEY HIT THE RED
TRACK, THE BETTER WAS THE
IMPROVEMENT, A VERY SIGNIFICANT
CORRELATION AND THIS WAS REALLY
I REPRINT WITH THE 2 COHORTS AND
WE FINE GOT THE LAST COHORTS SO
WE GOT THEM ONCE THE TRACT WAS
ESTABLISHED.
SO THAT WAS SUPER REWARDING TO
SEE THIS CHECKS OUT IN UNDEAN
DATA AS WELL, BUT WHAT WAS MORE
EXCITING IS THAT OTHER PEOPLE
HAVE REPLICATE THE FIEBDINGS
WELL, WE PUBLISHED WITHIN GBS
THAT'S OPEN AND AVAILABLE,
EVERYBODY CAN DOWNLOAD THE EXACT
TRACT DEFINITION AND AT THE MT.
SINAI GROUP OF HELEN AND
[INDISCERNIBLE] DID SO AND THEY
DID OVERLAY THE VOLUMES OF
THEIREN IT PATIENTS AND AGAIN
THE MORE TRACT WAS MODULATED,
THE BETTER THESE PATIENTS DID.
IN FACT 4 TOTAL REPLICATIONS
CAME WITHIN THE FIRST 6 MONTHS.
SO THERE'S THE PAPER I JUST
MENTIONED MY SMITH ET ALAND
THERE WAS ANOTHER REPLICATION IN
[INDISCERNIBLE] WITH 8 PATIENTS
SHOWING THE SAME TRACT VERY
CLEAR CORRELATION WITH OVERLAPS
AND THEN THERE WAS A STUDY FROM
[INDISCERNIBLE] IN BRISBANE, AND
YOU SEE THIS TRACT EMERGE HERE
AND THE OVERLAP WITH OUR
PUBLISHED TRACK WAS NOT
SIGNATURESSATIVE CANT BUT WAS
ASSOCIATE WIDE OUTCOMES AND
FINALLY WHAT I FIND MOST
INTERESTING IS THAT KAREN
JOHNSON, [INDISCERNIBLE] LOOKED
AT 28 PEASHTS WITH 5 CENTERS
WITH TOURETS SYNDROME BUT WITH
OCD IN THE GPIs TO GET ANOTHER
TARGET AND THE OUR TRACT WAS
MODULATED AT THE BETTER
IMPROVEMENT SIGNIFICANTLY IN
THESE TOWERET PATIENTS IN THE
OBSESSIVE COMPULSIVE BEHAVIOR.
SO THIS IS GREAT.
NEXT STEPS TO FURTHER VALIDATE
IS TO DO IT BLINDEDLY.
SO I WAS QUITE EXCITED THAT
SAMIR, [INDISCERNIBLE] WAS OPEN
FOR SUCH A COLLABORATION AT PAY
LORA RODRIGUEZ UNIVERSITY.
SO THEY HAVE 10 ADDITIONAL
PATIENTS NONAPOPTOTIC THE SEEN
AT ALL BY NOW FROM THIS PROJECT
AND THEY SENT US THE
NEUROIMANNUALING AND SIMULATION
PARAMETERS IN A PLIENDED
PACKAGE.
WE DID NOT KNOW HOW THESE
PATIENTS DID, ALL WE HAVE THE
IMAGING AND WE RAN THEM THROUGH
THE TRACK MODEL AND PREDICKED
THE CLINICAL OUTCOMES AND WE
SENT BACK THE PREDICTIONS, AND
THEN, SMIR'S TEAM KNEW THE
ACTUAL CLINICAL OUTCOMES AND
COULD CORRELATE THE 2 AND VOILÀ,
IT IS REALLY EXCITING THAT THIS
WORKED, RIGHT?
THIS WAS REALLY PLIENDED.
WE HAD TO PUT OUR NICKEL DOWN,
WE HAD TO SEND OUR PREDICTIONS
TO PAY LORA RODRIGUEZ AND IT DID
WORK.
HE USED THEIR PATIENTS, THIS IS
OUR TRACT AND YOU REPLICATE THE
SAME WITH THE 10 NEW PATIENTS
FROM BAYLOR, YOU GET EXACTLY THE
SAME TRACT AGAIN WITH THE SAME
METHOD.
WE ALSO LOOKED AT FUNCTIONAL
CONNECTIONS LOOKINGA THE MORE
SYNAPTIC NETWORKS WITH THE SAME
TECHNIQUE USING FUNCTIONAL
CONNECT OMES, NOW AND CONNECTED
IN THE OCDDBS, AND THAT COULD BE
CRUCIAL FOR TRANSLATING FINDINGS
INTO THE NONINVASIVE STIMULATION
AROUND WHICH HAS BEEN
SUCCESSFULLY DONE IN GBS FOR
DEPRESSION AND TMS FOR
DEPRESSION AND BUT NOT YET FOR
OCD.
WE WROTE A REVIEW ON THIS ASK
LOOKED AT ALL THE DATA THAT IS
OUT THERE AND ATOMICAL ADULTS IN
NEUROMODDULATION AND FORMS, IT
TURNS OUT THAT THIS TRACT SEEMS
TO LINK DIFFERENT THERAPIES THAT
WE KNOW LIKE CAPSULEOT ME, AND
TMS, AND SO THIS SEEMS TO BE A
UNIFYING STRATEGIC BUNDLE THAT
IS HELPFUL.
AS NEXT STEPS THIS IS ONGOING
WORK NOW, QUITE PRELIMINARY AND
THIS IS WORK BY BARBARA
[INDISCERNIBLE] WHO IS A ROCK
STAR Ph.D. STUDENT IN MY LAB
IN BERLIN.
I WANT ON TO BRIEFLY SHOW IT.
WE EXTENDED TO COHORT, THERE ARE
SO MANY GREAT COLLEAGUES THAT
HELP WITH THIS I DID NOT HAVE
THE SPACE TO PUT PICTURES OF
EVERYBODY ON HERE BUT THIS IS A
GREAT COLLABORATIVE EFFORT
BETWEEN OUR MUCH BIGGER
COLLABORATION.
AND WE HAVE THE ELECTRODES
LOCALIZATIONS AND DIFFERENT
TARGETS NOW WITH THE A MUCH
BIGGER POWER HERE, THESE ARE THE
DIFFERENT COHORTS WE'RE
INCLUDING AND THESE ARE THE
ACTIVE SIMULATION SIDES, AND NOW
THE IDEA IS TO SEGREGATE THIS
TRACT INTO SPECIFIC SYMPTOMS,
RIGHT?
THE IDEA IS TO LOOK AT--JUST THE
GENERAL WIDE BOX TRACK BUT IF WE
LOOK AT SPECIFIC SYSTEMS CAN WE
FIND SPECIFIC CONDITIONS,
ANXIETY, DEPRESSION, GLOBAL
FUNCTIONING, SO HERE IT DOES
BETTER DEGRADATION GREEN CELLS
GET--I SO WE FIND DIFFERENT
PARTS OF IT TO RESPOND BET TORE
DIFFERENT SUBSYMPTOMS OF A OCD.
IT HAS SPECIFIC NETWORKING FOR
SUCCESSION ARE KIND OF LINING
WITH THE ORIGINAL TRACT WHILE
OBSESSION SEEM TO BE A BIT MORE
DAUNTLY CONNECTED AND THEN WE DO
SEE IN DEPRESSION, CRITICALLY
ALSO THE PROPER MEDIA FOREBRAIN
BUNDLE AND ALSO A BIT OR VENTAL
SESSIONS AND PLOABAL FUNCTIONING
IN GENERAL BEING THE MOST
VENTRAL CONNECTION HERE.
SO THE NEXT STEPS WILL NOW BE TO
USE IN INFORMATION TO
PERSONALIZE DEEP BRAIN
STIMULATION, RIGHT?
WE WANT TO DEFINE AND VALIDATE
THESE SYMPTOM NETWORKS THAT I'VE
SHOWN YOU FURTHER, ONCE WE HAVE
THEM, WE HAVE--WE HAVE
ESSENTIALLY A LIBRARY OF THESE
METE YORKS IN THE TEMPLATE SPACE
AND IF A NEW PATIENT COMES IN,
THIS IS A SLIDE FOR PARKINSON'S
DISOAZ WHERE WE ARE ALSO DOING
THE SAME THING, THAT PATIENT
COULD HAVE DIFFERENT SYMPTOM
INTENSITIES IN THIS CASE,
[INDISCERNIBLE], CAN YOU THINK
OF OCD OF COURSE, SOMEBODY WITH
A LOT OF ANXIOUS AND A LOT OF
OBSESSIONS BUT MAYBE NO
COMPULSES OR SIMILAR
DISTRIBUTIONS OF SIM TOMS, WE
CAN ALSO ASK THE PATIENT, WHAT
IS THE MOST ANNOYING SYMPTOM,
PARKINSON THAT IS EASIER, THERE
ARE SOMETIMES PATES THAT WOULD
CLEARLY SAY MY TREMOR IS LEADING
TO THE MOST BURDEN FOR ME VERSUS
YOU KNOW I CAN LIVE WITH
[INDISCERNIBLE] KINNIESIA AND WE
CAN MULTIPLY AND GET TO A
FUNCTION OF TARGETS WHICH
CIRCUITS WE WANT TO MODULATE
MOST.
NOW WE CAN AGGREGATE THESE
NETWORKS FOR EACH SYMPTOM FOR
THE PASHT AND PROJECT THEM TO
THEIR BRAIN AS A STEP IN
BETWEEN, WE CAN EVEN USE THE
PROFUSION DATA OF THAT PATIENT,
TO REFINE, YOU KNOW THE
PERSONALIZED TRACTS IN THAT
PATIENT'S BRAIN AND NOW WE CAN
SEE ONCE THE ELECTRODE IS
IMPLANTED WHICH CONTACTS
AUTOMATICALLY TO ENGAGE THE BEST
SYMPTOM SPECIFIC NETWORK FOR
THAT PATIENT.
WE CAN DO THE SAME WITH FMRI AS
WELL AND OF COURSE IT'S ALSO
USED EVEN TO IMFORP AND GUIDE
TARGETING TO REALLY DERIVE AT A
PERSONALIZED DEEP BRAIN
STIMULATION FOR EACH PATIENT
DEPENDING ON THEIR SYMPTOMS.
SO I WANT TO CONCLUDE AND I WILL
SAY THAT THE BRAIN NETWORKING
MAPPING CAN BEY PREDICTIVE OF
THE DBS OUTCOME AND I'VE SHOWN
THAT ACROSS MODELS AND OUTCOMES
AND TARGETS AND CENTERS.
IT CANNOT BE USED TO SEGGREGATE
THE HUMAN CHRONIC
[INDISCERNIBLE].
SO THE FIRST SLIDE I SHOWED
USING DBS ACROSS DIFFERENT
DISEASES AND DIFFERENT TRACTS, I
THINK IS ALSO JUST FROM A BASIC
SCIENCE PERSPECTIVE, WITH GREAT
TECHNIQUE THAT CAN HELP US
UNDERSTAND THE BRAIN BETTER, AND
THEN, LAST I SHOWED THAT SYMPTOM
NETWORK PLENDING COULD BE USED
TO PERSONALIZE DEEP BRAIN
STIMULATION.
AND MY PERSONAL AIM IS REALLY TO
LOOK CLIN CAM TRANSLATIONS, I
THINK ESPECIALLY THE WIDE BOX
TRACK, I THINK THE IT HAS BEEN
REPLICATED SO OFTEN NOW THAT IT
WOULD BE GREAT TO GO PROSPECTIVE
AND USE IT FOR SURGICAL PLANNING
TO TENTIALLY OR FOR
REPROGRAMMING TRIALS, SO, IF
THERE IS INTEREST THERE, PLEASE
DO REACH OUT.
I WOULD LOVE TO BE INVOLVED IN
SUCH A PROJECT AND WITH THAT I
WANT TO END.
THIS IS MY GROUP.
MY LABORATORY IS SPLIT BETWEEN
BERLIN AND BOSTON WITH, THIS IS
THE BOSTON TEAM AND THE BERLIN
TEAM WHILE [INDISCERNIBLE], THE
TEAM MOVE WITH ME, AND THERE'S
IF YOU ARE INTERESTED IN THESE
THINGS, THERE'S A NEW BOOK OUT
CALLED CONNECT TELOMERIC DEEP
BRAIN STIMULATION WITH ALL OF
THE METHODS WE USE FOR THIS
GREAT COLLABORATIVE EFFORT THAT
I HAD THE JOY OF EDITING.
THANK YOU SO MUCH FOR YOUR
ATTENTION.
I THINK THERE WILL BE NO ROOM
FOR QUESTIONS UNFORTUNATELY BUT
FEEL FREE TO REACH OUT VIA
E-MAIL OR TWITTER AND THANK YOU
VERY MUCH FOR YOUR ATTENTION.
[ APPLAUSE ]
>>[INDISCERNIBLE] TALKING ABOUT
CONCURRENT TMS AND MI IN DRUG
ADDICTION APPLICATIONS.
NTHANKS.
>>THANKS ALL FOR STICK TO THE
LAST TALK.
I KNOW IT'S A LONG WORKSHOP.
HOPEFULLY, PEOPLE WOULD ENJOY
MOST OF THAT.
SO, YEAH, JUST KIND OF FOLLOWING
THE PREVENTIVUOUS 2 SPEAKERS
ABOUT THE PACKET IDENTIFICATION
AND HERE I'M GOING TO TALK
ABOUT, THE IDENTIFYING THE
TARGETS IN SUBSTANCE USE
DISORDER OR ADDICTION, OKAY,
OKAY GREAT.
SO SUD FROM NEUROCIRCUITRY
PERSPECTIVE IT'S REALLY A
DISRUPTION OF MULTIPLE BRAIN
CIRCUITS OR NETWORKS UNDERLYING
THE VERY COMPLEX ADDITIONAL
BEHAVIORS AND THE ANIMAL MODEL
ALSO OFFERS A LOT OF OPPORTUNITY
TO UNDERSTAND THE DISEASE.
BECAUSE, FOR EXAMPLE, RATS HAVE
VERY ANALOGOUS BRAIN CIRCUITS,
BRAIN REGIONS.
AND ALSO FROM A LITTLE BIT OF A
MORE BROADER PERSPECTIVE S. U.
D. INVOLVES IN MULTIPLE STAGES
AND SUCH AS PINCHING,
INTOXICATION, WITHDRAWAL AND
EFFECTIVE NEGATIVE EFFECT AND
PREOCCUPATION AND ANTICIPATION.
SO IT'S VERY TRICKY FOR THE
TREATMENT NEUROMODDULATION BASED
TREATMENT.
SO FIRST WHERE TO STIMULATE AND
AT WHAT STAGE FOR EXAMPLE?
SO, THE TREATMENT FOR THE S. U.
D IS VERY CHALLENGING AS SHOWN
HERE, FOR THE PSYCHOSOCIAL
INTERVENTIONS.
YOU CAN SAY FOR DIFFERENT TYPE
OF SUDs, THE DROP OUT IS VERY
HIGH, 35% AND THE RELAPSE RATE
AFTER TREATMENT RESULTS VERY
HIGH, LIKE 70%.
SO, SO AS WE SEE IN THIS
WORKSHOP SEVERAL
NEUROMODDULATION APPROACH BEING
DEVELOPED AND IN PARTICULAR TMS
HAS BEEN APPROVED BY FDA FOR THE
DEPRESSION XREEMENT AND FOR OCD
TREATMENT.
SO STILL A CHALLENGE IN THE TMS
BASED TREATMENT FOR SUD AS I
MENTIONED, YEAH, SO 1 IS WHERE,
WHERE TO FIND THE OTHER TARGETS
IN THE BRAIN BECAUSE THERE'S
NUMEROUS POTENTIAL REGIONS SUCH
AS DLPC, MEDIAL PFC, OFC INSULAR
AND SO ON, ALSO VERY IMPORTANT
IN EACH OF THOSE REGIONS, THE
HETEROGENERATED AITY IS PRETTY
HIGH.
SO I WILL SHOW YOU A LITTLE BIT
IN A LATER SLIDES.
AND ANOTHER CHALLENGE IS IN THE
TMS SPACE, THERE ARE SO MANY
PARAMETERS SUCH AS FREQUENCY,
INTENSITY, DURATION, TEMPORAL
PATTERNS, AND SO ON.
AND ALSO AS I BRIEFLY MENTIONED,
WHERE TO STIMULATE, YOU KNOW
DURING THE DIFFERENT BRAIN
STATES.
SO IN THE SUD, THERE ARE AT
LEAST 3 STAGES IN THE CYCLE SO
WHERE TO STIMULATE IS VERY
IMPORTANT.
SO, YE, WITH THOSE KIND OF
BACKGROUND, SO I JUST WANT TO
TELL YOU OUR RECENT EFFORTS IN
THIS DIRECTION AND SOME ARE
BEING PUBLISHED, SOME ARE STILL
ONGOING, SO THE FIRST 1 IERK
DENTIFY TARGETS BASED ON
NEUROIMAGING AND DISEASE RELATE
TD BEHAVIOR, IN THIS CASE, DRUG
RELAPSE.
SO AS WE KNOW, THIS IS A STUDY
IN DEPRESSION AND WE KNOW THAT
EVEN WITH THE DLPC FR EXAMPLE,
THE TREATMENT IS HETEROGEANIOUS,
AS THE PREVIOUS SPEAKER
MENTIONED, THE ANTICORRELATION
WITH [INDISCERNIBLE] INDICATES
SOME TREATMENT EFFICACY IN
DEPRESSION.
SO, YEAH, DEPRESSION IS
RELATIVELY KNOWN FOR SOME
REGIONS, BUT FOR SUD IT'S MUCH
LESS NOW.
SO WHERE TO STIMULATE?
IF WEB CONNECTED DO A VERY
SYSTEMATIC SEARCH, FOR OPTIMAL
TARGETS WOULD IT BE FINANCIALLY
COSTLY.
LIKE SAY IF IT'S A HUNDRED
POTENTIAL SITES IT'S ALMOST
IMPOSSIBLE TO DO THAT SO WE
PROPOSE A 2 STAGE APPROACH.
THE FIRST STAGE WE
SYSTEMATICALLY OR COMPREHENSIVE
EXPLORATION FOR THE REGION FOR
INSURANCE AND RELATED TO THE
DISEASE AND SECOND STAGE
HOPEFULLY WE CAN NAIL DOWN ONLY
A FEW POTENTIAL TARGETS.
SOPHISTICATED THAT'S THE
STRATEGY WE ARE USING.
SO THIS STUDY ALREADY PUB LESHED
SO THIS--THIS WAY IS A FOCUSING
ON A DPLC, AND BASICALLY,
THE--THERE'S A COHORT OF COCAINE
TREATMENTS, YOU KNOW SEEKING
COCAINE USERS.
SO AFTER A FEW WEEKS OF
PSYCHOSOCIAL TREATMENT, DID FMRI
AND THEN FOLLOW UP ABOUT 24
WEEKS FOR THE RELAPSE.
SO JUST KEEPING IN MIND THERE'S
NO TMS HERE, IT'S JUST MORE
CONVENTIONAL PSYCHOSOCIAL
TREATMENT.
BUT WHAT WE TRY TO DID IS FIND
THE CIRCUITS AND TREME THEM AS
OUTCOME AND USE THEM AS TARGET
FOR THE TREATMENT.
SO AS CAN YOU SEE FROM THIS
SURVE BASICALLY IS A REMAINING
[INDISCERNIBLE] AFTER THE
TREATMENT SO YOU CAN SEE
FOLLOWING ABOUT 24 WEEKS AND
THEY ARE DROPPING TO ABOUT LEAK
ABOUT 20% REMAINING, SO YOU CAN
VIEW THIS AS KIND OF A SURVIVE
CURVE IN CLINICAL SETTINGS.
SO, THEN, BASED ON THAT, WE
CAN--WE DEVELOPED A MODEL
LOOKING AT TO LINK THE
FUNCTIONAL CONNECTIVITY AND THE
TREATMENT OUTCOME.
SO IN THIS CASE, WE ARE USING
THE REGRESSION MODEL WHICH IS A
REVENTIVE TR THE SURVIVAL
BEHAVIOR, SO,--SO, HERE, NOW,
WE--WE PUT IT, IT SEEMS WE DON'T
KNOW WHERE IN THE DPLC WOULD BE
OPTIMAL FOR SUD TREATMENT, SO WE
PUT IT ABOUT A HUNDRED REGION WE
CHOSE OVER THERE AND WE JUST
GONE THROUGH THIS AND WITH VERY
STATISTICAL CORRECTIONS FOR THE
MULTIPLE COMPARISON AND WE FOUND
ONLY 3 OUT OF A HUNDRED REGIONS
SHOWING SIGNIFICANT PREDICTION
FOR THE RELAPSE AND THEN WE LOOK
AT 1 REGION ACTUALLY ON THE LEFT
SIDE OF THE DPLC, AND WE CHECK
THE LITERATURE AND FIND IT VERY
INTERESTING THIS SIDE, AND THIS
AREA OF INTEREST, IMAIF USA I
LET OF CONFIDENCE THAT THIS
METHOD MAY WORK.
ANDY SHOWED A LOT ON THE RIGHT
SIDE OF DPLC, WHICH WE SEARCH
LITERATURE NEVER BEEN USED FOR
THE ADDICTION SO IT COULD BE
POETIC TEBTIAL SITES FOR THE
TREATMENT.
SO IF WE WANT TO GO LOOK IN
DETAIL, WHAT'S--WHAT KIND OF
BRAIN CIRCUITS INVOLVED IN THIS
FIRST AREA OF INTEREST,
BASICALLY, THEY WOULD SHOW
PROTECTIVE CIRCUITS AND THE
RISKS CIRCUITS PROTECTIVE MEANS
STRONGER CONNECTIVITY, IT WOULD
HAVE, IT WOULD HAVE A LONGER I
MEEP ABSTINENCE TIME AND RISK
CIRCUITS WILL BE UP THE OTHER
WAY,A ROUND SO THE PROTECTIVE
SECOND QUARTER UTRS BASICALLY
INVOLVED IN THIS EXECUTED
CONTROL NETWORK, WHICH WE
BELIEVE IS INVOLVED IN
CONNECTIVE CONTROL AND THE RISKS
CIRCUITS IS MORE INVOLVED IN THE
INFORMAL NETWORK, AND WE BELIEVE
THAT'S PROBABLY SERVING AS THE
KIND OF DRIVE CIRCUITS, DRIVE
FOR THE [INDISCERNIBLE].
SO, YEAH, WE ARE--WE ARE STILL
WORKING ON THAT, AS YOU SEE IN A
PREVIOUS TALK, I THINK THE TALK
IN THE PREVENTIVE YOIS SESSION
WE MOVED THIS TO OTHER BRAIN
REGIONS LIKE OFC AND OTHER
INSULAR OR SOME OTHER REGIONS.
SO SECOND PROJECT WE ARE DOING
IS, THIS IS NOT NOT BEEN
PUBLISHED YET, I JUST WANT TO
SHOW YOU SOME--YEAH, SO THIS
IS--THIS IS BASED ON THE
META-ANALYSIS, SO THE CONCEPT IS
TO TARGETING THE ENTIRE
PATHOLOGICAL NETWORK, SO, FROM
A--FROM A MECHANISM, TYPICALLY
YOU SEE A SET OF BRAIN REGIONS,
IT'S ALTERED FROM THE HEALTHY
CONTROL OR SOMETHING LIKE THAT,
SO, HOW CAN YOU TAKE CARE OF
THIS MULTIPLE REGIONS INTO YOU
KNOW YOUR TARGET IDENTIFICATION.
SO HERE, I JUST GIVE YOU
EXAMPLE.
THIS IS THE META-ANALYSIS FOR
DEPRESSION AND IT'S SHOWING
MULTIPLE REGIONS, YOU KNOW,
HYPER OR HYPOACTIVATED.
SO THEN THE GOAL IS TO FIND A SO
CALLED MODLATTORY NETWORK.
SO HERE JUST GIVE YOU EXAMPLE,
HOW DO WE DERIVE THIS AND DEFINE
THIS MODLATTORY NETWORK.
SO FOR EXAMPLE, YOU PUT A TMS
COIL SOMEWHERE HERE AND WITH
POSITIONING AND ORIENTATION, AND
WE CAN SIMULATE THE EFIELD AND
HOW DO YOU FEEL WILL GENERALLY
EFFECTS PROPAGATE TO THE WHOLE
BRAIN, AND ANAPOISE THIS
STIMULATION NETWORK.
SO THIS IS A LOT OF WAYS TO DO,
AND WE CAN USE FOR EXAMPLE,
STRUCTURAL CONNECTIVITY, AND WE
CAN USE FUNCTIONAL CONNECTIVITY
AND WE CAN USE INDIVIDUALIZED
CONNECTIVITY OR WE CAN USE GROUP
CONNECTIVITY, RIGHT?
SO, IT JUST AS A FIRST STAGE, WE
JUST USED A GROUP LEVEL RESTING
STAGE FUNCTIONAL CONNECTIVITY AS
ESTIMATE FOR THIS PROPAGATION
NETWORK.
SO 1--SORRY, SO ONCE WE HAVE
THESE 2 NETWORKS PATHODPLOJ
LOGICAL NETWORK AND MODLATTORY
NETWORK, THEN WE--OUR NETWORK OF
TARGETING IS BASKLY TO LET THE
MODLATTORY NETWORK KIND OF
COMPARE ON THE PATHOLOGICAL
NETWORK, SO FOR EXAMPLE, A
PATHOLOGICAL NETWORK IF IT'S
HYPER ACTIVATED WE BRING TO BING
IT DOWN, SO IF IT'S HYPOWE TRY
TO BRING IT UP, SO THAT IS A
MATHEMATICAL MODEL FOR THAT SO I
WON'T GO THROUGH THAT.
SOPHISTICATED WITH THAT METHOD,
CAN YOU IMAGINE JUST ON A COHORT
OF SUBJEKS, THE WAYS TMS FOR
EXAMPLE, TMS TREATMENT AT
DIFFERENT LOCATIONS, YOU WILL
SEE, THEY WILL GENERATE
DIFFERENT MODLATTORY NETWORK AND
THEY WOULD END UP WITH DIFFERENT
EFFICACYS IN THE TREATMENT.
AND SO, IN THIS CASE, YOU KNOW
HOPEFULLY, WE WILL ANAPOISE THIS
KIND OF SITUATION SO WE HAVE
THIS SO CALLED NETWORK OF
TRACKING ACCURACY BASICALLY IT'S
JUST A DEGREE OF MODLATTORY
NETWORK OF CONTACTS ON A
PATHOLOGICAL NETWORK.
SO HOPEFULLY THIS NETWORK OF
TARGETING ACCURACY WOULD BE
CORRELATED WITH A CLINICAL
TREATMENT AND EFFICACY HERE.
SO THIS IS JUST ALL HYPOTHESIS
OR MODELING, RIGHT?
SO THEN WE JUST MOVE ON TO GET
US ON EXISTING DATA SO WE--YEAH,
WE FOUND 1 PAPER FROM A FRENCH
GROUP, THEY NICELY, THEY HAVE
THE TREATMENT, TMS TREATMENT AND
THEY HAVE FOR INDIVIDUAL
SUBJECTS, THEY HAVE A LOCATION,
AND ORIENTATION AND SO ON, IT'S
EVERYTHING.
SO THIS IS THE PERFECT PLACE TO
KIND OF TEST OUT THIS METHOD.
SOPHISTICATEDY IN THIS CASE, WE
HAVE TWEIVE SUBJECTS AND AS I
MENTIONED DIFFERENT LOCATIONS
AND DIFFERENT ORIENTATION FOR
THE TMS COIL.
SO THEN WE JUST, YOU KNOW PUT IT
OUT VARIOUS INFORMATION IN THE
MODEL AND WE SEE CORRELATED BUT
SPECIFICALLY EXPLAIN THE
VARIANTS SO IT'S SOMETHING
THERE, RIGHT?
THEN WE--WE TRIED TO DO ANOTHER
DAT SITE, THE SAME GROUP IN THE
FRENCH GROUP, THEY DID THE TMS
TREATMENT ON THE AUDITORY ON THE
HALLUCINATION PATIENT, THE
SCHIZOPHRENIA PATIENTS, AUDITORY
HALLUCINATION, SO THEY HAVE A 15
SUBJECT, AGAIN THEY HAVE THE
LOCATION, AND ORIENTATION OF THE
TMS COILS AND WE PLUG INTO OUR
MODEL AND WE FOUND THAL CASE,
EXPLAINS EVEN MORE VARIANTS
ABOUT 30% OF THE VARIANTS.
SO I THINK IT'S ENCOURAGING AND
IF WE HAVE A LARGER DATA SET AND
WE WILL BE--WE WILL BE VERY
HAPPY TO TEST THIS OUT TO SEE
HOW THIS MODEL WORKS.
ADDITIONALLY, YEAH, THIS MODEL
CAN ALSO PREDICT IN THIS
HALLUCINATION PATIENTS WE CAN
PETITION THE BEHAVIOR, IN THESE
PATIENTS.
SO YEAH, THIS IS THE ONGOING AND
NOT PUBLISHING YET, WE'RE STILL
WORKING ON THAT AND THE OTHER
PROJECT I WANT TALK ALSO IS AN
ONGOING PROJECT.
SO THIS IS TO IDENTIFY THE NEW
MODULATION SITES BASED ON ANNUAL
MODELS, YOU WANT TO SAY ARE YOU
A LITTLE BIT CRAZY ABOUT THIS
BECAUSE WE'RE WORKING ON HUMANS
BUT ANIMAL MODELS, THE RAT
MODELS CAN GET A PRETTY GOOD
BEHAVIOR FEATURES OF THE DISEASE
AND ALSO HAVE VERY
[INDISCERNIBLE] BRAIN REGIONS
AND CIRCUITS SO I THINK IT'S NOT
TOO CRAZY TO DO THIS.
SO 1 WAY TO DO THIS IS AS YOU
KNOW THE SUD INVOLVES KEY
FEATURES AND ARK DICTION IS
COMPULSIVE DRUG TAKING, SO WE
PUBLISHED A PAPER BY USING
ANIMAL MODEL TO MIMIC THISY
ABOUT HAIEVER, COMPULSIVE DRUG
BEHAVIOR, SO HERE WE HAVE RATS
AND WE TRAIN THEM TO
ADMINISTRATE DRUG AND THEN
AFTERWARDS WE GIVE THEM
PUNISHMENT, IN THIS CASE,
INCREASE THE CURRENT OF THE FOOT
SHOCK, SO, NOW WE--WE WILL SEE
BEHAVIOR WISE, AND WHEN YOU
TRAIN THEM TO DO SELF-NUTRITION,
SO THEY ARE TAKING DRUG MORE AND
MORE BUT GETTING TO STATUS STATE
AND THEN YOU GIVE THEM FOOT
SHOCK AND ALSO INCREASE THE
STRENGTHS.
SO YOU WILL SEE OVERALL, THEY
WERE REDUCED THE DRUG TAKING AND
FROM THIS CURVE WE CAN DEFINE
THE SO CALLED COMPULSIVITY
INDEX.
SO BASICALLY JUST THE DRUG
TAKING IN THE END OF THE
PUNISHMENT PHASE NORMALIZED BY
THE DRUG TAKING IN THE END OF
THE SELF-ADMINISTRATION PHASE,
SO IT'S VERY SIMPLE INDEX, FOR
THIS INDEX, YOU SEE, FOR RATS,
WITH THE HIGH COMPULSIVITY THEY
WILL HAVE HIGH CI, BASICALLY.
SO, OKAY, SO, THIS IS JUST
AVERAGE CURVE FOR A GROUP OF
RATS BUT IF WE LOOK AT
CAREFULLY, WE KIND 2 SUBGROUPS
HERE SOY 1 GROUP IS RESISTANT OF
THE FOOT SHOCK SO EVEN THOUGH
THEY FACE PUNISH AM, THEY KEEP
TAKING DRUG, THIS IS THE ORANGE
GROUP, THE OTHER GROUP IS THE
BLUE GROUP.
SO THEY JUST GIVE UP TAKING
DRUGS.
YES, TO THE PUNISHMENT, SO WE
LOOK AT THE BRAIN CIRCUITS, WE
DID FMRI ON THESE RATS AND LOOK
AT BRAIN CIRCUITS AND WE FUNDED
BASICALLY 2 CIRCUITS, 1 IS
CALLED GOLD CIRCUITS IT'S FROM
OFC TO THE STRIATAL, SO
BASICALLY THEY ARE INCREASING,
THE CONNECTIVITY IS INCREASING
AFTER SELF-ADMACHINEISTRATION
AND SLIGHTLY DECREASED AFTER
PUNISHMENT BUT NOT MUCH
DIFFERENCE BETWEEN THESE 2
GROUPS.
THE OTHER CIRCUMSTANCE UTRS
WOULD CALL THE STOP CIRCUITS OR
KIND OF A CONTROL CIRCUITS IT'S
FROM A PRELIMBIC TO STRIATAL.
SO THESE 2 CIRCUITS DECREASED
DECREASED AFTER CONNECTIVITY OF
THIS CIRC UT DECREASED AFTER
SELF-ADMINISTRATION TRAIPING BUT
YOU KNOW, INTERESTINGLY, AFTER
THE PUNISHMENT, THE RESISTANT
GROUP IS KEEPING DECREASING BUT
THE SENSITIVE GROUP COMES BACK A
LITTLEIT SO WE CAN ALSO PUT THEM
TOGETHER TO LOOK AT THE BALANCE
OF THESE 2 CIRCUITS SO WE SEE
AGAIN, THESE 2 RATS COMPARED TO
THE SALIENT GROUP THAT DEVIATED
QUITE A BIT AFTER
SELF-ADMINISTRATION BUT AFTER
THE PUNISHMENT, THE RESISTANT
GROUP JUST KEEP THE SAME, KEEP
DEVIATED BUT THE SENSITIVE GROUP
IS KIND OF COMING BACK A LITTLE
BIT.
ALSO, WE CAN LOOK AT THE
BEHAVIOR WISE, AS I MENTIONED,
WE DEVELOPED A SO CALLED
COMPULSIVITY INDEX, CI, SO, ONLY
THIS RESISTANT GROUP THE IMAGING
CORRELATED WITH THE BEHAVIOR,
NOT THE SENSITIVE GROUP.
SO I THINK THIS IS A NICE MODEL
AND SPEAKS TO THE INDIVIDUAL
DIFFERENCES, IN DRUG ADDICTION.
AND THEN, SO, JUST BACK TO THE
MODULATION, SO HOW DO WE DO
THIS, WITH GO IN WITH STOP
CIRCUITS.
AND 1 WAY WE CAN DO IT IS WE'RE
USING CHEMO GENETIC OR OPTICAL
IMAGES O GENETIC STIMULATION AND
WE TRY TO UNDERSTAND A MORE KIND
OF CELLULAR MECHANISM.
IN THIS CASE I GIVE EXAMPLE
USING CHEMO GENETICS AND SO WE
CAN TRY TO ENACTIVATE THIS ORC
CIRCUITS BUT KIND OF SUPPRESS
THE ORC CIRCUITS BUT BRING UP
THE PRELIMBIC CIRCUITS IF WE CAN
DO THAT.
SO THEN WE CAN ASK SOME
QUESTIONS HERE SO WE CAN ALTER
THE CIRCUITS BE RESTORED AFTER
THIS NEUROMODDULATION, CAN THE
BEHAVIOR, WITH THE DRUG TAKING
BEHAVIOR BE ELIMINATED AND IF,
OH YES, THEN WHAT IS OPTIMAL
NEURAL MODULATION PROT COLFOR
THE TREATMENT.
SO, AS YOU SEE IN THE FIRST DAY
[INDISCERNIBLE] SHOWED A VERY
NICE DEVELOPMENT OF THE FOCUS
TMS ON RAT BRAIN SO THE NEXT
STEP, OBVIOUSLY, WE WILL MOVE TO
MORE KIND OF TRANSLATIONAL
NEUROMODDULATION.
OBVIOUSLY THE CHEMO GENETIC BE
DIFFICULT TO DO ON HUMANS SO WE
TRY TO USE TMS, FOCAL TMS AND
TRY TO ANSWER THE SAME
QUESTIONS, HERE.
AND THAT'S--ALSO THE ONGOING,
IT'S NOT PUBLISHED YET.
SO IT'S JUST BRIEFLY SUMMARIZE,
SO I THINK I IDENTIFY THE NEW
INSIGHT SYSTEM VERY IMPORTANT
STEP FOR THE SUCCESS OF THE
TREATMENT IN THE SECOND OF--FOR
PSYCHIATRIC DISORDERS INCLUDING
ADDICTION AND JUST FOR SOME
DISEASE WITH VERY LIMITED
KNOWLEDGE OF THE TARGETS, SUCH
AS ARK DICTION, SO WE PROPOSE
SOME STRATEGIES TO FIND A
POTENTIAL TARGETS ON THAT.
SO JUST SUMMARIZED HERE THE
FIRST IS TO USE NEUROIMAGING AND
A DISEASE-RELEVANT SYMPTOMS OR
BEHAVIOR.
THE SECOND IS TARGETING THE
ENTIRE PATHOLOGICAL NETWORK FROM
BASED ON THE META-ANALYSIS, AND
THE THIRD 1 IS ANIMAL MODELS
WITH TRANSLATIONAL POTENTIALS.
THAT'S ALL I HAVE.
THANK YOU VERY MUCH.
[ APPLAUSE ]
NTHAT WAS REALLY INTERESTING.
YOU KNOW, CAN YOU SAY ANYTHING
MORE ABOUT THE PUNISHMENT
RESISTANT TYPE AS WELL IS
SOMETHING YOU CAN USE AS A
PREDICTOR OR IS THERE EVIDENCE
THAT THEY DON'T FEEL THE
STIMULUS AS WELL?
ANYTHING MORE TO UNPACK IN TERMS
OF WHICH ANIMALS ARE FALLING
INTO THAT CATEGORY?
>>SORRY.
SORRY SOME ECHOES WOULD YOU
REPEAT THE LITTLE BIT YOUR
QUESTION?
>>SURE.
I WAS JUST WONDERING IF THERE'S
SOMETHING SPECIAL ABOUT THE RATS
THAT ARE RESISTANT TO
PUNISHMENT?
>>YEAH.
WE DON'T KNOW WHY, THEY ARE JUST
COUSINS, THEY ARE SHOWING QUITE
DIFFERENT BEHAVIORS AND THAT IS
PRETTY WELL TO HUMANS ABOUT
MAYBE 20% OF THE PEOPLE USING
DRUG END UP DEVELOPED INTO
DEPENDENCE OF DRUG.
SO, YEAH, WE REALLY DON'T KNOW
THE CAUSE OF THAT, BUT YEAH, WE
FOUND--WE FOUND THIS KIND OF
SUBGROUPS, SO IT DEPENDS ON
MANIPULATIONS FOR EXAMPLE, YOU
CAN MANIPULATE THE STRENGTH OF
THE CURRENT FOR THE FULL SHOCK
AND YOU CAN--CAN YOU HAVE 20% OR
80%, YOU CAN HAVE 50%, SO, BUT I
THINK INTERESTINGLY, THEY--YEAH,
LOOKS LIKE BESIDES THE BRAIN
DEHAIEVER DISRCHES THEY'RE ALSO
SHOWING BRAIN CIRCUIT
CONNECTIVITY DIFFERENCE.
SO YEAH, THAT'S SOMETHING VERY
INTERESTING FOR US AND ALSO
MIGHT BE USEFUL TO GUIDE THIS
TREATMENT.
FOR EXAMPLE, THE TREATMENT
SEEKING PATIENT COMES INTO THE
CLINIC IF WE CAN MEASURE THEIR
CONNECTIVITY OR SOME TASK OR
WHATEVER, THEN IF WE HAVE CAREER
IF AN IDEA CAN SEPARATE THE
PATIENTS INTO SUBGROUPS.
ONE GROUP SUCH AS MAYBE NOT A
GOOD CANDIDATE FOR SOME
TREATMENT, BUT IT COULD BE GOOD
FOR OTHER TREATMENT, FOR EXAMPLE
IN YOUR CASE, YOU FIND
[INDISCERNIBLE] AMYGDALA, SMAIB
SOME PATIENTS WOULD BE JUST GOOD
FOR 1 OF THEM.
>>YEAH, YEAH.
>>SO, IT'S OBVIOUSLY IT'S A
LONG WAY FOR PARTICULAR ANIMAL
MODELS, IT'S A LONG WAY TO
GETTING TO KREK THE SITUATION.
>>AWESOME, THANK YOU.
>>THAT'S GREAT, SO I HAVE A
GENERAL QUESTION, SO YOU
PRESENTED THE VERY NORMAL WAY TO
IDENTIFY THOSE THERAPEUTIC
TARGETS.
AND YOU KNOW FROM THE PATIENT
PERSPECTIVE, FROM THE ANIMAL, MY
QUESTION IS WHAT IS YOUR IDEA
ABOUT HOW YOU CAN EPITHELIAL
GREAT ALL THE INFORMATION AND
YOU KNOW FROM DIFFERENT LEVEL
AND THEN BECAUSE IF YOU WANT TO,
LIKE EACH PATHWAY OR EACH--IT'S
GOING TO INVOLVE A LOT OF WORK
SO AND FROM YOUR POINT OF VIEW,
HOW YOU CAN BRING THE ANIMAL
DATA TO HELP WITH THE CLINICAL
OR HOW YOU INTEGRATE ALL THE
INFORMATION.
>>YEAH, YEAH, THANKS.
YEAH.
>>YEAH, SIMILARLY, AS--IT'S
ALONG WAY TO GO, ANIMAL MODELS,
WE USE THE [INDISCERNIBLE], I'M
NOT ANIMAL MODEL GUY, BUT NIDA
HAS SOME VERY GREAT ANIMAL
BEHAVIOR MODEL GUY.
SO ALAN [INDISCERNIBLE] IS NOW
ANIMAL MODEL IS PERFECT.
CANNED WHAT AND THAT'S TYPICALLY
TALK ABOUT HIM.
SO YEAH, ANIMAL MODELS, I THINK
TYPICALLY TO MIMIC THE IMPORTANT
HUMAN DISEASE BEHAVIOR, RIGHT?
SO IN THIS CASE FOR EXAMPLE,
IT'S COMPULSIVE DRUG TAKING
BEHAVIOR, SO WE ARE USE ALSO
USING OTHER MODELS IF ARE
EXAMPLE, THE RELAPSE MODELS TO
MIMIC THE RELAPSE BEHAVIOR.
SO, YEAH, IT'S A--TO BE HONEST,
I ALSO STUDIED THIS A FEWIERS
AGO, BUT --I THINK IT'S PRETTY
PROMISING AT LEAST YOU KNOW
CURRENT PROGRESS.
BUT I THINK IT'S STILL, IT'S A
LONG WAY TO GO FROM RODENTS TO
HUMANS AND PROBABLY IF POSSIBLE,
WE COULD DO SOME MONKEYS, YOU
KNOW BETWEEN AND KIND OF
GRADUALLY TRANSLATE THIS
KNOWLEDGE INTO THE
[INDISCERNIBLE].
SO THE CHALLENGE FOR SOME
DISEASE, LIKE ADDICTION OR MAYBE
SOME OTHERS, YOU DON'T HAVE ANY
IDEA, YOU KNOW WHERE, OR HOW TO
DO THIS MODULATION, PEOPLE JUST
LIKE TO TRIAL AND ERROR AND HEY,
SOMETIMES THEY'RE LUCKY ENOUGH
TO BE VERY SUCCESSFUL, BUT A LOT
OF UNSUCCESSFUL PEOPLE DO
STUDIES THAT PROBABLY NOT
PUBLISHED.
SO YEAH, SO, YEAH I DON'T KNOW
IF I ANSWER YOUR QUESTION BUT I
THINK, YEAH, IT'S A LONG WAY BUT
HOPEFULLY WE ARE MOVING TOWARDS
THAT.
>>OKAY, SO NOW WE END THE PANEL
DISCUSSION SESSION.
CAN THE PANELISTS COME TO THE
PODIUM, DR. WOODS,
DR. [INDISCERNIBLE] AND 2
INDUSTRY REPRESENTATIVE AND ALSO
NIH [INDISCERNIBLE].
>>I THINK WE HEARD A LOT OF
DEVELOPMENT IN ACADEMIA, AS I
THINK WE WILL HAVE 2
REPRESENTATIVES HERE FROM
INDUSTRY, [INDISCERNIBLE].
AND NIH DR. [INDISCERNIBLE].
OKAY, AND THAT'S IT AND THERE
ARE [INDISCERNIBLE] SO I THINK
WE WILL START WITH NIH
PERSPECTIVE BECAUSE YOU KNOW I
THINK NE H HAS A LOT OF RFAs
THAT EVERYBODY'S VERY
INTERESTED.
>>ACTUALLY DOCTOR
[INDISCERNIBLE] SHE'S THE P. O.
SHE'S THE BOSS OF ALL THE
NEUROEMAGING PROGRAMS, YEAH IT
WAS WONDERFUL TO HEAR YOU TALK.
CAN YOU OFFERER SPECTIVE?
>>YEAH, SO I WOULD WOULD SAY IT
WAS LONG BUT I DO HAVE A COUPLE
OF IDEAS ABOUT SOME REALLY
RELEVANT PROGRAMS FOR THIS SPACE
IN TERMS OF NIMH PROGRAM, WE
JUST LAUNCHED A NEW PROGRAM THAT
I'M RUNNING CALLED THE
MULTIMODAL NEURAL THERAPIES
PROGRAM THAT WAS JUDGE UOF THE
LAUNCHED THIS SPRING AND I THINK
IT'S REALLY RELEVANT FOR A LOT
OF WHAT'S BEEN DISCUSSED TODAY
INCLUDING DEVICE SPACE
INTERVENTIONS IN COMBINATION
WITH IMAGING MODALITIES AND JUST
APPROXIMATE MULTIPLE POETIC
DALLASCOWBOYS.COMITYS IN
COMBINATION AND IN ORDER TO
UNDERSTAND VARIOUS SORTS OF
POSITIVE SYNERGYS THAT CAN
HAPPEN ACROSS MODALITIES IN
TERMS OF STIMULATION BUT ALSO IN
TERMS OF BIOMARKER DEVELOPMENT
ISSUE UNDERSTANDING HOW WE CAN
ENGAGE THE TARGET MORE RECISELY
AND UNDERSTAND TARGET ENGAGEMENT
IN NEW WAYS.
THE OTHER THING I WANT TO TALK
ABOUT IS, I DID NOTICE THAT
THERE WAS SOME REALLY
INTERESTING WORK HERE LOOKING AT
IMAGING IN COMBINATION WITH
INVASIVE STIMULATION MODALITIES,
WE ALSO HAVE A NEW FUNDING
OPPORTUNITY THROUGH THE BRAIN
INITIATIVE CALLED BRAIN BEHAVIOR
QUANTIFICATION AND AND I'M ALSO
FAMOUS FOR THAT PROGRAM AND WHAT
WE'RE LOOKING TO DO THERE IS USE
MULTIMODAL COMBINATIONS TO
REALLY CAPTURE BEHAVIOR AND LINK
IT SIMULTANEOUSLY TO LINK IT TO
BRAINS IN HUMANS AND THAT IS NOT
NIMH SPECIFIC THAT CAN BE IN ANY
DISEASE POPULATION AND A RANGE
OF PATIENTS ACROSS HEALTH
STATES.
IT IS LASTER TECHNOLOGY
ORGANIZATION I WANT TO MENTION,
DISCIPLINARY NOTICE THAT THERE
WERE MANY ENGINEERING REORIENTED
TALKS HERE AND IN TERMS OF
DEVICE DEVELOPMENT, I JUST
WANTED TO PLUG OUR NEWLY
LAUNCHED BLUE MED TECH PROGRAM,
THIS IS ALSO A TRANSNIH EFFORT.
THE GOAL HERE IS TO TAKE A NEWLY
DEVELOPED TECHNOLOGIES AND
ADVANCE THEM OREAC CELLERATE
THEM INTO A PROGRAM INTO FIRST
AND HUMAN NEWS TRANSLATION AND
GOING FROM PROTOTYPES ALL THE
WAY UP INTO FIRST IN HUMAN
TRANSLATION AND THERE ARE A
NUMBER OF NUMBER OF ICs
CURRENTLY FOUND IN THAT SPACE
INCLUDING NIMH BUT ALSO NIDA,
NIBIB, NICHD, AMONG OTHERS, SO
REALLY EXCITING STUFF, I'M ALSO
CURRENTLY SERVING AS THE INTERIM
CONTACT FOR THE BLUEPRINT MED
TECH PROGRAM, ANY FOLKS HERE WHO
ARE INTERESTED IN ANY OF THESE
PROGRAMS PLEASE REACH OUT TO ME
I DON'T HAVE A CARD WITH ME BUT
YOU CAN FIND MY NAME IN THE
PROGRAM AND JUST GOOGLE AND IT
YOU WILL SEE--YOU WILL FIND ME
BECAUSE MY NAME IS PRETTY
DISTINCT.
THANK YOU.
>>[INDISCERNIBLE]--HOW DO YOU
START WHICH 1 MOST PROMISE TO
TRANSLATE, I KNOW TO TRANSLATE
FROM DBS, TO SURE, SO THE WAY I
THINK ABOUT IT, WELL, MAYBE A
LITTLE BIT INTRODUCTION WAS ALSO
GIVEN BACKGROUND, I GOT MY
PPh.D., PENN STATE, I AM PART
OF THE COMMUNITY BUT AFTER THAT
I JOINED MED TRONNIC TO WORK ON
MI --SO ABOUT 3 YEARS AGO JOINED
ABNORMALITIES SOT BUT DOING THE
SAME TECHNOLOGY TRANSFER BUT
MORE ON THE MANAGEMENT SIDE NOW,
SO THAT'S A LITTLE BACKGROUND.
THIS IS REALLY 2 ROIs IN THE
SCIENTIFIC COMMUNITY WE TALK
ABOUT WHICH 1 I WANT TO TARGET
FOR THIS DISEASE, RIGHT AND THEN
THERE'S ALSO ROI FOR BUSINESS
WHICH IS RETURN ON INVESTMENT
RIGHT?
FROM PRETTY MUCH ALL COMPANIES
THAT'S A BIG ROIs, OKAY, SO
BUSINESSES HAVE TO HAVE THE
MONEY TO SURVIVE, RIGHT, SO WHEN
WE HAVE THESE 2 ROI OVERLAP AS
MUCH AS POSSIBLE, THAT'S THAT'S
WHERE THE OPPORTUNITY ARE.
SO THINK ABOUT HOW FOR
EXAMPLE,--IF THEY DON'T HAVE
INVESTED IN THAT NEW DEVICE IT'S
JUST FOR EXAMPLE, IF WE TAKE
EXISTING DEVISITING, JUST MOVE
TO A SLIGHTLY DIFFERENT TARGET.
THAT PHYSICIAN SURGEON STILL
FEEL VERY COMFORTABLE TO DO, SO
YOU DON'T HAVE TO CHANGE THE
DEVISITING, YOU DON'T HAVE THE
CHANGE THE PROCEDURE THAT
DRASTICALLY BUT YOU CAN TREAT A
BIG DISEASE FOR EXAMPLE,
DEPRESSION, YOU KNOW, BACK IF
THEY HAVE TO CHANGE IF THEY FIND
A GREAT TARGET BUT THEN, YOU
HAVE TO CHANGE SAY PROCEDURE,
IMPLANT PROCEDURE OR YOU HAVE TO
CHANGE IT TO HARDWARE, RIGHT THE
SYSTEM ON OR SOFTWARE THEN THE
COSTS BECOME MORE TO RETURN, YOU
KNOW ON THE INVESTMENT IS A
LITTLE BIT LESS.
SO, WHEN YOU GUYS DO, WHEN THE
COMMUNITY ESPECIALLY LIKE MED
TECH, IT IS PROBABLY HELPFUL TO
THINK ABOUT 2 IOIs.
I KNOW YOU ARE REALLY GOOD AT
YOU KNOW FIRST ROI, BUT ALSO
THINK ABOUT FROM THE BUSINESS
POINT YOUR ROI THAT'S GOING TO
HELP MAYBE, I DON'T KNOW, MAYBE
EVEN HELP YOU SELECT ALL THESE
DIFFERENT TARGETS, NETWORKS.
>>HOW CAN YOU--YOU GUYS THOUGHT
OR HAVE ACADEMICS CALL YOU SAY,
I HAVE A GREAT TARGET, A GREAT
TRIAL.
>>COULD YOU PLEASE IDENTIFY
YOURSELF BY NAME AFTER YOU
SPEAK, THERE'S NO NAME TITLES OR
ANYTHING HERE.
>>HMM?
>>CAN YOU IESHES DENTIFY
YOURSELF BY NAME WHEN YOU SPEAK.
>>YEAH, SORRY.
>>YEAH,.
>>MY MAIM IS [INDISCERNIBLE].
SO I'M SENIOR R&D MANAGER WITH
THE ABBOT NEUROMODDULATION.
>>[INDISCERNIBLE] SCOTT, TARGET
ACADEMIC PROPOSE TO YOU, YOU
SHOULD TRANSLATE THIS.
>>PROBABLY WOULD START WITH THE
MARKET SIZE, RIGHT IF YOU TALK
ABOUT DEPRESSION OR TALK ABOUT
IF IT'S A VERY SMALL OFTEN
DISEASE, PROBABLY COMPANIES
WOULD BT EVEN LOOK AT IT.
IF THE MARKET IS BIG ENOUGH,
THEN SAY, OKAY, WHERE ARE YOU
AT?
RIGHT?
IF IT'S STILL IN THE LAB
TESTING, THAT'S A HARD FOR
COMPANY TO SPONSOR.
IF HEY, I HAVE A SMALL
VISIBILITY STUDY IN HAD YOU
MANS, THE RESULTS REAL
PROMISING, THEN, THAT'S PROBABLY
WORTH THE TALK START THEN COME
DOWN TO OKAY, HOW MUCH MONEY YOU
NEED, WHAT KIND OF OUTCOME, HOW
LONG IT'S GOING TO TAKE, IT
ALWAYS HELPS TO HAVE SOMEBODY IN
THE COMPANY THAT YOU KNOW,
RIGHT?
LIKE IF I DON'T KNOW YOU, THEN
OF COURSE I PROBABLY WON'T BE
ABLE TO SIT HERE, RIGHT SO HUMAN
CONNECTION WITHIN THE COMPANY,
ALWAYS HELP.
SO IT'S NOT INDUSTRY IS NOT YOU
KNOW JUST BLACK BOXES.
COME DOWN DEPENDING ON EACH
INDIVIDUAL COMPANY AND THEIR
STRATEGY AND KNOWING SOMEBODY
INSIDE ALWAYS HELPS.
NTHANK YOU, DO YOU WANT TO
COMMENT BECAUSE YOU ARE MORE IN
BETWEEN, RIGHT?
YOU ARE MORE THE RESEARCH
PRODUCTS?
>>THAT'S RIGHT.
YEAH, SO OUR COLLEAGUES AT ABBOT
ARE KIND OF COVERING THIS SPACE
AND I AM HENRY--
>>YOU NEED TO TURN ON.
>>SO, SORRY.
>>HELLO.
YEAH, SO OOM HENRY I'M THE
SCIENTIFIC DIRECTOR FOR ROGUE
RESEARCH.
MANY OF YOU KNOW US AS SORT OF A
COMPANY THAT BUILDS TOOLS FOR
THOSE INVOLVED IN NONENVASIVE
BRAIN STIMULATION, WE'RE BASED
IN MONTREAL, SORT OF A SPINOFF
OF THE MONTREAL NEUROLOGICAL
INNSITUTE AND THE FUNDAMENTALS
OF COMPANY SPEAK TO YOUR
QUESTION WHEN YOU SPEAK TO
TARGETING ENGAGEMENT SORE
SELECTING WHAT PATHWAYS TO
PURSUE COMMERCIALLY.
OUR METHODOLOGY HAS BEEN TO
BUILD TOOLEDS IN CONJUNCTION
WITH RESEARCHERS, EVERYTHING WE
DO IS A REQUEST BY A RESEARCHER
OR REQUEST BY THE FIELD AT LARGE
AND THEN AS THOSE TOOLS MATURE
SO DOES OUR OUTLOOK, OUR
TECHNOLOGY AND OUR DIRECTION.
SO, HISTORICALLY, WE'VE ALSO
PROVIDED PROVIDED RESEARCH TOOLS
BECAUSE THE FIELD WAS PERHAPS
NOT SET ON THE TARGET AND THE
METHODOLOGY AND WE PREFER NOT TO
GET YOU TO THE WRONG PLACE
CONSISTENTLY EVERY TIME, THAT
WOULD BE SORT OF ILL USE OF THE
TOOLS.
NOW, AS THE FIELD HAS MATURED
AND THINGS LIKE RESTING STATE
MRI CONNECTIVITY ANALYSIS, HAVE
SORT OF PROVIDED UTILITY FOR
CLINICAL APPLICATIONS, NOW WE'RE
DEVELOPING THE TOOLS, AND YOU
KNOW FOLLOWING THE FIELD,
FOLLOWING OUR CUSTOMERS THAT WE
WELCOMERRED WITH ALL THIS TIME,
TO YOU KNOW WE'RE THE SIDE THAT
DEVELOPS THE TOOLS, SO, IN TERMS
OF RESTING STATE MRI, DEVELOPING
SORT OF A CLINICAL ORIENTATION
WHERE PEOPLE CAN MAKE USE OF
THAT INFORMATION, SEND THAT
INFORMATION IN TERMS OF
MULTISITE STUDIES DOING
EVERYTHING THAT WE CAN TO REDUCE
VARIABILITY ACROSS STUDIES WHICH
SEEMS TO BE, YOU KNOW 1 THING
CAN AFFECT THINGS QUITE I BIT.
SO, YOU KNOW, BUILDING A ROBOTIC
HOLDER FOR FOCUSED ULTRASOUND OR
FOR TMS TO REDUCE SORT OF
OPERATOR VARIABILITY, PARTNERING
WITH COLUMBIA DUKE UNIVERSITY
PRODUCE NEXT GENERATION TMS
DEVICE THAT CONTROLS FOR
PARAMETER THAT VARIES ACROSS
DEVICES, THE PULSE SHAPE AND THE
PULSE WHIP.
AND YOU KNOW THE MULTIMODAL
APPROACH WE'VE SEEN HERE WITH
PEOPLE INTEGRATING EEG, ET
CETERA WE'RE AWZ WORRY BODY
NEURONAVIGATION AND TMS, NOW
NEXT GENERATION MAY INTEGRATE
EEG CHANNELS, WE'RE NOT AN E, G
COMPANY BUT THE RESEARCH HAS
PUSHED US TOWARD THE APPROACH SO
I THINK IT'S JUST IMPORTANT FOR
US TO HAVE AN EAR ON THE GROUND
TAKEN--THEY TO BE VERY TIED TO
THE RESEARCHERS TO UNDERSTAND
WHAT TOOLS THAT I NEED AND TO
UNDERSTAND THAT WHERE THEY ARE
IN THAT SORT OF RESEARCH TO
CLINICAL TRANSLATION PATHWAY.
WE ALSO HAVE A VETERINARY SIDE
OF THE COMPANY WHERE WE PAIK USE
OF THESE KIND EVER TRANSLATION
COMOPPOSITE BEHAVIORIAL
PHENOTYPENTS AND IF WE TELL
WHERE OUR CUSTOMERS ARE IN THEIR
RESEARCH AND UNDERSTANDING THEN
WE CAN PROVIDE THE BEST RESEARCH
TOOLS OR MAKE THAT LEAP WITH
THEM TO THE CLINICAL SPACE
TOGETHER.
>>YOU ARE MORE FLEXIBLE, YOU
ARE WILLING TO SERVE THE SMALLER
COMMUNITY?
>>YEAH THAT'S RIGHT.
THAT'S WHAT I MEAN BY OUR WHY
COMPANY, THE REASON FOR EXISTING
IS TO DO COOL NEUROSCIENCE TO
HELP OUR CUSTOMERS, ACCOMPLISH
THEIR GOALS, TO HAVE A GOOD TIME
SOLVING THESE COMPLEX AND
INTERESTING PROBLEMS SO WE DON'T
REALLY SEE OURSELVES AS A
NEURONAVIGATION OR TMS COMPANY,
WE TRY TO BE FLEXIBILITY AS THE
RESEARCHERS ARE FLEXIBLE, AS
OPPORTUNITIES RISE OR FALL AS
MODALITIES MAKE THEMSELVES MORE
USEFUL, PARTICULARLY IN THE
SPACE OF BIOMARKER IDENT ISKSZ
AND PERHAPS SOFTWARE TOOLS WE
CAN BE FLEXIBLE FOR WHAT'S
SERVING THE RESEARCHER THE MOST.
SO THAT KIND OF FLEXIMENT,
WILLINGNESS TO MOVE QUICKLY.
THERE ARE BUSINESS DECISIONS
THAT GO INTO THAT FOR EXAMPLE,
KEEPING OUR RESEARCH AND SORT OF
THE CLINICAL ASSPIRRATION
SEPARATE WE FOUND THAT WHEN
COMPANIES IN THE NONINVASIVE
SPHERE MAY LEAN HEAVILY
CLINICALLY, THE RESOURCES BECOME
DIVERTED FROM RESEARCH AND THE
INFORMATION THEY'RE GATHERING
FROM THERE.
SO FROM A BUSINESS PERSPECTIVE
WE MAKE A DECISION TO SILO THOSE
OFF TOW WE CAN REMAIN
FLEXIBILITY FROM THE RESEARCH
SIDE WHILE CREATING THE CLINICAL
TOOLS THAT OUR CUSTOMERS FEEL
ARE READY FOR DEPLOYMENT AND
READY FOR PRIME TIME.
>>AUDIENCE WANTS TO ASK THE
PANEL SOME QUESTIONS.
>>HI, I WAS WONDERING IF FOLKS
ON THE PANEL THOUGHT WHAT WE
SHOULD BE CHASING FOR NEURAL
MODULATION TO REALLY OPTIMIZE
OUR OUTCOMES?
SO WHAT IF IT'S THE CASE THAT
THERE'S NOT GOING TO BE A REALLY
CLEAN BIOMARKER FOR SOMETHING,
AN ABNORMALITY THAT WE CAN
DETECT AT THE INDIVIDUAL LEVEL
BUT NEVERTHELESS WE'RE BUILDING
UP NEUROMODDULATION EVIDENCE
THAT CERTAIN SYMPTOMS MOVE AND
WE THINK WE HAVE TRACTABLE
TARGETS FOR THAT SIMILAR TO WHAT
ANDY WAS SUGGESTING IN HIS TALK
THAT MAYBE YOU START WITH ASKING
THE PATIENT, YOU SAY WHAT DO YOU
THINK IS BOTHERING YOU THE MOST
AND IF WE HAVE EVIDENCE FOR
MODULATING THAT, THAT'S WHAT WE
SHOULD FOLLOW INSTEAD OF
KEEPING, CHASING THESE
BIOMARKERS THAT ARE JUST SO
ELUSIVE BUT, AS ALL OF US ARE
WORKING ON NEUROMODDULATION,
EVEN IF IT'S AN ANIMAL MODEL OR
FOR A DIFFERENT DISORDER AND YOU
SAY OOH, WE'RE TRYING TO
STIMULATE HERE FOR PARKINS SONS
AND WE SHIFTED MOOD, LET'S TRY
THAT NOW, IF WE'RE A MOOD SORT
OF TARGET, DO YOU GUYS THINK
THAT THAT'S MORE TRACTABLE AND
SHOULD BE OUR FOCUS OR ARE WE
JUST NEEDING TO REFINE AND
FURTHER IMPROVE AND SUBTYPE AND
FURTHER CHASE IMAGING BASED
ABNORMALITY?
>>SURE.
I'LL GO FIRST.
I THINK IT'S A PHENOMENAL
QUESTION AND I DON'T THINK WE
HAVE A CLUE WHAT WE'RE CHASING
RIGHT NOW IF I'M BEING HONEST.
I THINK WE'RE ALL TAKING STABS
IN THE DARK AND I THINK DR. YANG
SAID WE'RE FIRING OFF RANDOMLY
ATTEMPTING TO FIND SOMETHING
THAT WORKS.
AND WHEN FACED WITH THAT I THINK
IT'S NOT GOING TO BE A MAGIC
BULLET, IT WON'T BE 1 THING, WE
ULTIMATELY KNOW IT WILL NOT BE 1
MARKER TO RULE THEM ALL.
I THINK WE NEED TO HAVE ROBUST
APPROACHES AND I ALSO THINK WE
NEED TO HAVE BETTER DAILY BASIS
THEA SHARING APPROACHES.
WE STRUGGLE WHERE WE CAN RUN A
TRIAL, IT CAN TAKE US 5 YEARS TO
FINISH THAT TRIAL ASK THEN
SOMEONE ELSE RUNS A TRIAL BUT WE
CAN'T ACCESS THE DATA AND YET WE
COULD ANSWER ALL THESE QUESTIONS
CAN NOT WASTE ANOTHER
$10 MILLION ON THAT TRIAL IF 5
YEARS IF WE COULD ONLY ACCESS
THE T1, OUTCOMES, ET CETERA.
SO EFFORTS ACROSS FIELDS TO
CREATE UNIFIED FIELD DATA
SHARING SO WORK LIKE THIS IS
HAPPENING IN THE ENIGMA WORKING
GROUPS BUT IT'S VERY INFANTILE
IN THE PROGRESSION AND BETTER
SUPPORT FROM NIH, INDUSTRY AND
ARES FOR THESE KINDS OF
APPROACHES, I THINK WILL HELP US
IESHES DENTIFY WHAT THE BEST
TARGET IS SOY DON'T KNOW THAT WE
ACTUALLY KNOW IN ANY TARGET AT
THIS POINT.
WE HAVE GOOD HINTS, BUT WE NEED
MORE SCIENCE AND WE NEED MORE
DATA.
JUST MY OPINION.
>>IS THIS ON?
OKAY, SO, I WANT TO GIVE SOME
PERSPECTIVE WORKING ANN ENGINEER
IN SOLVING ANY PROBLEM.
I THINK THE GOAL HERE IS TO
UNDERSTAND BRAIN AND
PATHOPHYSIOLOGY AND FROM THE
ENGINEER'S PERSPECTIVE WE DON'T
UNDERSTAND SOMETHING UNLESS WE
CAN BUILD IT.
AND SO, YOU KNOW IT'S ALWAYS
BEEN MY DREAM TO BUILD A MODEL
OF THE BRAIN, EITHER HARDWARE OR
SOFTWARE AND BE ABLE TO SIMULATE
THESE DIFFERENT CONDITIONS,
SIMULATE DIFFERENT STIMULATION
CONDITIONS ON TOP OF A HEALTHY
OR PATHOLOGICAL BRAIN.
AND WE'RE NOT THERES ARE YET,
WE'RE NOT EVEN CLOSE TO HAVING A
VERY REALISTIC MODEL OF THE
BRAIN ON A NEURON LEVEL BUT
THERE ARE ONGOING EFFORTS.
FOR EXAMPLE, FROM THE CELL ATLAS
PROJECTS AND THE ALAN
EN--STRATEGIESITUTE IS PUTTING
TOGETHER AND CATALOGING ALL OF
THE CELL TYPES IN THE BRAIN TO
SOME OF THE EUROPEAN BRAIP
PROJECTS THAT ARE TRYING TO USE
FUNCTIONAL DATA USING STRUCTURAL
DATA TO INFORM A VIRTUAL BRAIN
MODEL.
THIS IS THE VIRTUAL BRAIN
PROJECT THAT THE EUROPEAN, SOME
OF THE INITIATIVES THERE IS
STARTING.
AND SO, FOR ME, I'M INTERESTED
IN SHIFTING AT LEAST OUR
RESEARCH IN THAT DIRECTION IS
BEING ABLE TO BUILD A BRAIN AND
MANIPULATE IT STARTING WITH
SIMULATIONS.
>>WELL I WILL JUST SAY VERY
BRIEFLY, IS THIS ON, IS THIS, I
WILL SAY BREFLY THAT OUR
ULTRASOUND BEING SORT OF THE NEW
KID ON THE PLOK HERE THAT IN
MANY WAYS IT'S EASIER FOR US
WATCHING THE OTHER MODALITIES
AND LEARNING AND SEEING WHERE DO
WE NEED TO GO, BUT IN MANY WAYS
- IT IS HARDER FOR US BECAUSE WE
NEED TO IDENTIFY WHAT'S OUR
ADDED VALUE THAT, IS NEW OVER
THE OTHER MODALITIES SO I THINK
THAT'S PRETTY IMPORTANT FOR US
WHERE WE NEED TO GO.
>>FOLLOWING THE DISCUSSION THAT
YOU ALREADY HAVE, I THINK THAT
WE ALL HERE ARE LOOKING FOR THE
SAME BASICALLY QUESTION AND THAT
WE ARE TRYING TO SEE, WHATEE CAN
DO AND EACH OF US IN OUR LABS,
WE ARE TRYING TO FIND KIND OF
TARGETS AND WE ARE TRYING TO
VALIDATE THEM, BUT THE QUESTION
I HAVE IS BEYOND WHAT WE ARE
DOING BEYOND WHAT WE ARE DOING
IN OUR INDIVIDUAL LAB, THE
QUESTION IS HOW CAN WE DO
SOMETHING ON AT THE COMMUNITY
LEVEL.
THIS IS WHAT WE TRY TO DO
TOGETHER, THE LAST 3 DAYS,
GETTING TGHTS, DISCUSSING WHAT
OTHER DIFFERENT LABS ARE DOING
AND THE REQUESTY IS WHAT IS
GOING TO HAPPEN AFTER THIS
MEETING?
WHAT ARE THE POTENTIAL KIND OF
BENEFITS WE CAN MAKE FROM THESE
NETWORKING ACTIVITIES THAT WE
ARE DOING HERE?
I WILL ASK A QUESTION FROM
PEOPLE HERE, HOW MANY OF YOU
WOULD BE INTERESTED TO ATTEND
THIS MEETING IN 2 YEARS SAME
TIME, HERE IN NIH?
JUST RAISE YOUR HANDS.
SO, SO THAT IS KIND OF AN
ONGOING DISCUSSION NERMALS
OF--AND COMPARED TO MANY OTHER
MEETINGS WE ATTENDED IN THE LAST
COUPLE OF YEARS, I THINK THAT
KIND OF THE UNIQUE FEATURE OF
THIS MEETING THAT WE HAVE ALWAYS
BEEN DISCUSSING ABOUT THE
CENTRAL CORE OF BASICALLY MRI,
AS BEING IN THE CENTER OF THE
DISCUSSIONS, AND DIFFERENT
MODALITIES AROUND MRI TRYING TO
SEE HOW WE CAN LEARN FROM EACH
OTHER, AS KIM MENTIONED HOW WE
CAN LEARN FROM OTHER MODALITIES.
WHAT PEOPLEY IN OTHER MODALITIES
ARE DOING AND THE REQUESTY IS
OKAY, HOW WE CAN GO BEYOND THAT?
IS THERE ANY CHANCE WE CAN
CONTINUE THE DISCUSSION, IS
THERE ANY CHANCE WE CAN START TO
EVEN WRITE PAPERS, MAKE NOTES
ABOUT THE TAXONOMY, ABOUT THE
TERMINOLOGIES THAT YOU HAVE BEEN
DISCUSSING ABOUT CURING LAST
COUPLE OF DAYS WE HAVE BEEN
DISCUSSING ABOUT THOSE DOSE
RESPONSE RELATIONSHIP.
BUT WE HAVE DIFFERENT MEANINGS
FOR WHAT WE CALL DOSE AND WHAT
WE CALL RESPONSE AND IS THERE
ANY CHANCE WE CAN GET TOGETHER
IS KIND OF DEFINE THE SPACE
AROUND DOSE RESPONSE OR OTHER
TECHNICAL DETAILS WE ARE
INTERESTED.
WHAT ARE THE KIND OF CROSS TALKS
BETWEEN DIFFERENT MODALITIES
THAT WE HAVE IN A FEW YEARS
FOCUS ULTRASOUND BUT WE HAVE IN
TMS HOW WE CAN LEARN FROM EACH
OTHER AND CAN WE CONTINUE
DISCUSSION BEYOND WHAT WE ARE
DOING HERE AND THAT IS SOMETHING
INTERESTING TO SEE HOW WE CAN GO
BEYOND THAT.
>>THAT'S EXACTLY THE NEXT STEP
WE WANT TO TALK ABOUT, DO WE
WANT TO CONTINUE THIS MOMENTUM
TO HAVE THIS MEETING LIKE EVERY
OTHER YEAR, NOT EVERY OTHER DAY,
BUT THE TOPIC CAN BE CHANGED
SLIGHTLY ALONG THE DEVELOPMENT
OF THE FIELD, BUT IN GENERAL, I
THINK IMAGING NEUROMODDULATION
AND TECHNICAL DEVELOPMENT AND
CLINICAL APPLICATION, THOSE ARE
THE KEY WORDS, YEAH, I'M, YEAH.
A LOT OF WORK I'M PRETTY SURE.
IF SOMEONE WANTS TO TACK A
LEADER FOR IT, BUT I'M HAPPY TO,
IF NOBODY WANTS TO, I AM HAPPY
TO DO IT AGAIN, BUT YEAH, YEAH,
I THINK THAT'S SOMETHING WE
SHOULD THINK ABOUT.
>>SO WE WILL--
>>FOR PEOPLE IN AUDIENCE,.
>>HI, SO I JUST WANTED TO ADD
TO THAT I THINK THERE HAS BEEN
SIMILAR KIND OF CONFERENCES THAT
START WITH AN IDEA AND BUILD,
AND SO JUST TO KIND OF GIVE A
PARALLEL EXAMPLE, I THINK THE
DBS THINK TANK SORT OF STARTED
THIS WAY WHERE THERE WERE A
GROUP OF PEOPLE WITH A SPECIFIC
NICHE INTERESTED IN DEVELOPING
TARGETS AND THEY GOT TOGETHER AT
OAKINS UNIVERSITY OF FLORIDA AND
EVENTUALLY THEY
CERTAINLY--CERTAINLY VOLVED THAT
FROM EACH MEETING AND EACH
ADVANCEMENT, THEY WOULD PUB LESH
A GROUP PAPER ON WHAT IS THE
MOST UPDATED INFORMATION THAT
PEOPLE IN THE COMMUNITY COULD
USE.
SO JUST THINKING SIMILARLY,
EITHER A COMMUNITY SO GROUP
CONFERENCE PAPER TO SAY THIS IS
WHAT WE ARE ACHIEVINGAs A
FIELD AT THIS TIME VERSUS AN
OPEN PLATFORM AS STEVE WAS
SUGGESTING WHERE WE ARE
CONTRIBUTING COLLECTIVELY TO AN
AREA WHERE WE CAN COLLECTIVELY
PUT THE TAGHTA TOGETHER WHETHER
POSITIVE FINDINGS OR NEGATIVE SO
WE DON'T, YOU KNOW WASTE MONEY
OVER AND OVER AGAIN AND I THINK
AS COME OUT AS SAYING WE'RE ALL
DOING A VERY SIMILAR THING AND
LEARNING FROM EACH OTHER AND SO
PROBLEM SOLVING PROBLEMS A LOT
EASIER WHEN WE ACROSS DISEASES
ARE ASKING SIMILAR APPROACHES
AND CAN COME UP WITH A MORE
UNIFORM PIPELINE TO OPTIMIZE AND
IMPROVE EFFICIENCY, REALLY IN
ADVANCING DISEASES.
SO, JUST THINKING ABOUT HOW TO
BUILD BETWEEN CONFERENCES.
>>SORRY, THAT'S EXACTLY WHAT
ANDY HAVE BEEN THINKING ABOUT,
TALKING ABOUT, IS THE 1
POSSIBILITY IS TO FORM A STUDY
GROUP FOR EXAMPLE IN ISMRM, IT
HAS SEVERAL STUDY SITE GROUPS
AND THAT'S 1 POSSIBILITY,
ANOTHER IS TO PROPOSE SYMPOSIUMS
IN CONFERENCES, IN OHPM, ISMRM,
OR BRAIN STIMULATION AND SO ON.
SO, YOU KNOW PAST COUPLE YEARS,
DANNY AND I PROPOSED A COUPLE IN
OHPM AND ISMRM BUT WE WILL BE
HAPPY TO DO IT AGAIN, I GUESS.
YEAH, SO THOSE ARE THE THINKINGS
THAT WE HAVE.
>>SO I THINK WE SEND OUT AURE
VEY, TOGETHER WITH THE NICE
GROUP PICTURE WE TOOK ON MONDAY.
YOU WILL RECEIVE A SURVEY TO
BRAINSTORM IDEAS WE WANT TO HEAR
BACK FROM THEM, YEAH, IT'S A
COMMUNITY EFFORT.
YEAH, OKAY.
>>I JUST WANT TO COMMENT ON
YOUR PREVIOUS QUESTION, I REALLY
LIKE YOUR BLACK BOX DIAGRAM.
I THINK TRIAL AND ERROR, THAT'S
HOW HUMANS LEARN, RIGHT?
WE HAVE--WE CAN TAKE LIKE A
DIFFERENT TIERS TO ME IS HOW I
THINK ABOUT RIGHT, THE KEY ARE
THESE FOR BUSINESS?
CAN YOU PROVE IT WORKS, RIGHT?
IF YOU CAN, IT WORKS, THEN YOU
CAN HAND IT TO BUSINESS, GO MAKE
IT, MAKE A PRODUCT.
I KNOW IT WORKS, NOW YOU GO MAE
IT, RIGHT?
BUT THEN YOU GO INTO THE BLACK
BOX AND YOU ASK ALL THE WHYs,
SO IT'S VERY IMPORTANT FOR
RESEARCH AND THEN ONCE THEY
ANSWER ALL THE WHYs YOU DO
NEXT GENERATION OR BRAND NEW
STEPS BUT FIRST STEP IF IT COMES
FROM WORK, THAT'S HOW DBS, NOW
99% SURE IT'S GOING TO WORK,
THEN THAT'S BASICALLY, YOU'VE
DONE MOST HEAVY LEFTINGS' DONE
THEN THE TREY, ASSUME MARKET IS
BIG ENOUGH THEN I'M SURE
INDUSTRY, COMPANIES THE FIND A
WAY TO MAKE IT INTO PRODUCT.
>>OKAY, WE HAVE THE LAST ITEM.
PANEL PLEASE STAY, I THINK WE
HAVE,A WARDS CEREMONY?
YOU GUYS [INDISCERNIBLE] TO HAVE
YOU HERE.
SO WE HAVE 3 AWARDS TO GIVE TO
THE OTHER PRESENTATIONS, IT
COMES OUT VERY COMPETITIVE,
VERY, YEAH, [INDISCERNIBLE]
>>I WOULD LIKE TO SAY A FEW
WORDS ABOUT THE AWARDS FIRST OF
ALL THANK YOU VERY MUCH FOR
PRESENTATIONS.
I LEARNED A LOT, I HOPE YOU ALSO
LEARNED AND ENJOYED THE
WORKSHOP.
THIS WAS SO HARD, ALL THE
PRESENTATIONS ARE VERY GOOD.
I JUST WANT TO SAY THAT
INNOVATION, SCIENTIFIC QUALITY
AND PRESENTATION, AND MAYBE WE
CAN ANNOUNCE THE WINNERS.
>>YOU CAN.
>>ALL RIGHT.
ALL RIGHT.
SO WE HAVE LI-PANG NI, COMPUTER
MODELING MY IEE, AUDIENCE
DENTIFY TARGET FIST ARE ATTENT
DEPRESS ANT RTMS.
[ APPLAUSE ]
>>PLEASE POSE FOR A PICTURE.
[LAUGHTER]
>>[ APPLAUSE ]
>>SECOND PLACE WE HAVE
[INDISCERNIBLE] MR DUST
IMPLANTABLE NEUROINTERFACE WITH
DATA COMMUNICATION VIA MRI.
[ APPLAUSE ]
>>AND NUMBER 1 AREA BANKS MRI
FOCUSED CIRCUITRY FOR
ANESTHETICS IN THE BRAIN.
[ APPLAUSE ]
[LAUGHTER]
YEAH, SO THANK YOU ALL FOR STAY
SO LONG.
WE ARE REALEE GLAD TO BRING
TOGETHER EVERYBODY AND HOPEFULLY
THIS IS A START.
>>YEAH, I JUST WANT TO THANK
DANNY AND [INDISCERNIBLE] FOR
HAVING ME HERE.
I KNOW--E-MAILED ME PROBABLY IN
THE MIDDLE OF THE PANDEMIC ABOUT
A YEAR AND HALF AGO.
>>YEAH, IT TOOK A LONG TIME
IT'S A GRASS ROOTS.
IT'S A TRULY GRASS ROOT
ACTIVITY.
>>THIS IS THE FIRST 1.
>>IT'S ALWAYS HARDER.
>>IT TURNED INTO A MOVEMENT.
>>YEAH.
>>JUST REALLY APPRECIATE A LOT
OF HARD WORK INVOEVERLED.
>>THANK YOU.
LOOK FORWARD IT SEEING YOU IN
THE FUTURE AND WE WILL SEND YOU
SURSURVEYS TO LOOK FOR IT IN
YOUR E-MAIL.
[APPLAUSE ]