WELCOME TO THE WEDNESDAY
AFTERNOON LECTURE SERIES.
I'M CHRISTINE HUNTER, THE ACTING
DIRECTOR OF SOCIAL SCIENCE AT
NIH.
I'M THRILLED TO BE INTRODUCED
THE WALS SPEAKER, DAMIEN FAIR,
USING NEUROIMAGING TO
INVESTIGATE A HOST OF CONCERNS
IN COGNITIVE DEVELOPMENT IN
CHILDREN
TODAY'S SEMINAR IS SPECIAL.
THE NIH DIRECTOR'S LECTURES ARE
HAND PICKED BY THE NIH DIRECTOR
MONGS ALL WALS SPEAKERS.
BELIEVING TO BE THE MOST
EXCITING IN THE NATION.
OUR SPEAKER TODAY FITS THAT
DESCRIPTION.
AT THE UNIVERSITY OF MINNESOTA
DR. DAMIEN FAIR IS THE REDLEAF
ENDOWED DIRECTOR AT THE MASONIC
INSTITUTE FOR THE DEVELOPING
BRAIN AND HE IS PROFESSOR AT THE
INSTITUTE OF CHILD DEVELOPMENT
AND THE DEPARTMENT OF
PEDIATRICS.
HIS INTERESTS ARE AUTISM
SPECTRUM, ACHIEVEMENT GAP, CHILD
MENTAL HEALTH TO MENTION A FEW
TALKS.
HIS RESEARCH USING NEUROIMAGING
TO PROBE UNDERLYING BRAIN.
HE USES MRI AND RESTING STATE
MRI TO TEST TYPICAL AND ATYPICAL
POPULATIONS.
THERE ARE VARIOUS MRI TECHNIQUES
IN NEUROPSYCHIATRIC DISORDERS
SUCH AS ATTENTION DEFICIT
HYPERACTIVITY DISORDER.
THE GOAL OF THIS RESEARCH IS
INDIVIDUALIZE PATIENTS TO
DEVELOP DIAGNOSTIC, THERAPEUTIC
STUDIES.
HE RECEIVED HIS DEGREE IN
AUGUSTANA COLLEGE IN SIOUX
FALLS, MINNESOTA.
AND YALE UNIVERSITY OF MEDICINE
GRADUATING IN 2001.
HE REMAINED AT YALE BEFORE
MOVING TO THE WASHINGTON
UNIVERSITY SCHOOL OF MEDICINE IN
ST. LOUIS WHERE HE EARNED HIS
PH.D. IN 2008.
HE ACCEPTED THE POST DOCTORAL
POSITION AT OREGON HEALTH AND
SCIENCE UNIVERSITY AS AN
ASSISTANT AND ASSOCIATE
PROFESSOR.
IN JULY 2020, HE MOVED TO THE
UNIVERSITY OF MINNESOTA TO
ACCEPT HIS CURRENT POSITIONS.
I SHOULD NOTE THAT IN 2018, DR.
FAIR ALSO FOUNDED HIS OWN
COMPANY.
HE IS INVOLVED IN NUMEROUS
EDITORIAL BOARD AND SCIENCE
EDUCATION OUTREACH BOARDS AND
KNOWN AS A WONDERFUL MENTOR.
THE TITLE OF HIS TALK IS THE
FUTURE OF NON-INVASIVE
NEUROIMAGES IN THE ERA OF BIG
DATA.
THANK YOU, DR. FAIR, FOR BEING
WITH US TODAY
THANK YOU ALL FOR HAVING ME.
I'M HONORED TO SPEAK TO YOU
ABOUT SOME OF OUR MOST RECENT
WORK.
I ALWAYS LIKE TO START OFF MY
TALKS BY RECOGNIZING THE MASSIVE
AMOUNTS OF FOLKS AND
COLLABORATION IT TAKES TO DO
WHAT I DO TODAY.
IT IS VERY DIFFERENT WHERE I
TRAINED WHERE A LOT OF EXPERTISE
IS IN ONE LAB.
BECAUSE OF COMPLEXITY OF DATA
AND SYSTEMS IT REQUIRES AN ARMY,
CLINICAL SCIENTISTS, SOCIAL
WORKERS AND INFORMATICISTS AND
PHYSICISTS.
THIS IS A SMALL SAMPLE OF
COLLABORATORS THAT HAVE COME
TOGETHER TO CONDUCT A LOT OF THE
WORK YOU WILL BE HEARING ABOUT
TODAY.
ONE DISCLOSURE WAS ANNOUNCED, I
AM A CO-FOUNDER OF NOWS IMAGING.
I WON'T BE TALKING ABOUT ANY OF
THAT TODAY.
I LIKE TO PUT THAT OUT THERE TO
BE SAFE.
THERE ARE FOUR MAIN GOALS OF THE
TALK TODAY.
ONE IS I WILL BE GOING THROUGH A
BRIEF HISTORY OF COGNITIVE
NEUROSCIENCE, I CONSIDER MYSELF
IN A COGNITIVE NEUROSCIENTIST IN
THE STATE OF OUR FIELD.
I WILL BE TALKING ABOUT OUR NEW
AGE OF BIG DATA.
I PUT IN TWO FORMS, MANY
SUBJECTS AND LESSONS LEARNED
APPLICATIONS.
BIG DATA FEW SUBJECTS, LESSONS
LEARNED AND APPLICATIONS.
AND I WILL END WITH THOUGHTS AND
CONCLUSIONS FOR THE GROUP.
NOW, LIKE I SAID, I CONSIDER
MYSELF A NEUROSCIENTIST.
IT MIGHT BE COGNITIVE
NEUROSCIENTIST.
IT MIGHT BE HARD TO BELIEVE THE
ACTUALLY TERM COGNITIVE
NEUROSCIENTIST BORN OUT OF A
LATE NIGHT CITY TAXI RIDE IN NEW
YORK BY THOSE TWO FOLKS HERE.
THE TERM IS MEANT TO DESCRIBE AN
UNDERSTANDING HOW SPECIFIC
CHARACTERISTICS OF THE PHYSICAL
BRAIN SUPPORT VARIOUS ASPECTS OF
THE MINE.
-- THE MIND.
THE PHRASE EMERGED WITH VERY
BASE NEUROSCIENCE AND
PSYCHOLOGY.
IN THE LAST FIVE DECADES THE
FIELD HAS DEVELOPED IN WAYS ITS
FOUNDERS PROBABLY WOULDN'T
RECOGNIZE.
ONE OF THE ADVANCES THAT REALLY
PUSHED THE FIELD, THAT REALLY,
THE MERGING OF THE FIELD REALLY
BENEFITED FROM IS NON-INVASIVE
IMAGING, P.E.T. IMAGES AND
F.M.R.I.
THE TECHNOLOGIES ESSENTIALLY
CAPITALIZE ON THELIE -- THE
COUPLING OF NEURAL ACTIVITIENED
CHANGES IN THE BLOOD FLOW TO
GIVE US IMAGES INSIDE THE BRAIN
WITHOUT TOUCHING IT.
IT MADE THE GROWTH OF THIS SPACE
OR THIS FIELD REALLY POSSIBLE.
NOW, HERE IS A PICTURE OF A --
ONE OF MY FIRST STUDIES AS A
GRADUATE STUDENT.
I WAS TRYING TO DO DISSECT
PSYCHOLOGICAL PROCESSES OF
CHILDREN WITH PERINATAL STROKE.
WHEN THEY HAD A STROKE WHEN THEY
WERE FIRST BORN.
AND WHAT WE WERE DOING IS A
TRADITIONAL F.M.R.I. STUDY WHERE
YOU TAKE SEVERAL REPEATED
MEASURES WITHIN AN F.M.R.I.
EXPERIMENT TO DISSECT THESE
SPECIFIC PSYCHOLOGICAL
PROCESSES, IN THIS CASE RELATED
TO LEXICON PROCESSING OR WORD
GENERATION.
NOW, AT THAT TIME -- AND I
PULLED THIS PAPER OUT OF ONE OF
THE PAPERS I READ AS A GRADUATE
STUDENT AND MADE ME SO EXCITED,
THE PROMISE OF THIS NON-INVASIVE
IMAGING, THAT WAS 15 YEARS OLD
OR MAYBE LESS WAS SUPER
PALPABLE.
THIS IS THE EXCITEMENT OF WHAT
YOU COULD POSSIBLY DO WITH THIS
TECHNOLOGY WAS GREAT.
THE DISCUSSIONS OF THE FUTURE OF
FMRI CONJURED UP MIND READING
DEVICES USED AT THE AIRPORT
TERMINAL TO BACK ROOM OF THE
CORPORATE PERSONNEL OFFICE.
ONE RESEARCH FIRM WAS USING FMRI
TO PROBE WHAT CONSUMERS THINK
ABOUT THEIR CLIENT'S PRODUCTS.
THE EXCITEMENT WAS SUPER HIGH.
SINCE THEN WHILE FMRI IS
EXTREMELY VALUABLE IN
CHARACTERIZING BRAIN PATTERNS
AND FUNCTIONAL ACTIVATION
PATTERNS THAT ISOLATE VARIOUS
COGNITIVE PROCESSES I JUST
DESCRIBED, ESSENTIAL A CLINICAL
UTILITY RELATED TO THE EARLY
PROMISE HAS PRIMARILY BEEN
RELEGATED TO PRESURGICAL
PLANNING AND THEN IT IS NOT USED
WIDELY SPREAD IN THOSE DOMAINS.
THE IMPACT HAS BEEN RELATIVELY
SMALL, EVEN THOUGH IT IS A GOOD
FOR A LOT OF THE BASIC SCIENCES.
THAT'S 95.
THIS GUY BY THE NAME OF BRIAN
BISWAL LOOKED AT A DIFFERENT WAY
OF EXAMINING THIS TYPE OF FMRI.
INSTEAD OF DOING A TASK IN THE
SCANNER LOOKING AT PSYCHOLOGICAL
PROCESSES, HE EXAMINED THE BRAIN
WHEN IT WAS AT REST, NOT DOING
ANYTHING AT ALL.
THE SAME SYSTEMS THAT ARE
ACTIVATED DOING A TASK ARE
OSCILLATING WITH EACH OTHER WHEN
YOU ARE AT REST, NOT DOING
ANYTHING AT ALL.
WHAT THIS TOLD US IS A LOT OF
THE ORGANIZATIONAL FEATURES THAT
MAY EXIST WHEN YOU ARE SEEN
DOING A TRADITIONAL FMRI
EXPERIENCE CAN TELL US ABOUT
SIMPLE BRAIN ORGANIZATION.
BY THIS RESULT, KIND OF LAY
DORMANT IN THE FIELD FOR MANY
YEARS.
IT REALLY TOOK OFF IN 2005.
BY THIS PAPER BY MY PEER, ONE OF
MY STUDENT PEERS AT THE TIME,
MICHAEL FOX, IN THE LABORATORY
OF -- WHERE HE USED THIS
TECHNOLOGY TO HIGHLIGHT HOW
THESE VERY LARGE SCALE SYSTEMS
AND HOW THEY ARE COUNTERBALANCED
WITH OTHER SYSTEMS EXIST IN THE
BRAIN?
THIS TECHNOLOGY REALLY TOOK
OFF.
IN FACT, WELL, I WILL TALK ABOUT
THIS PART IN A SECOND.
NOW, MY INITIATE FORRAY INTO
THIS WAS BASICALLY FROM THIS
TRADITIONAL FMRI STUDY, TRYING
TO IDENTIFY PARTS OF THE BRAIN
THAT WERE REALLY IMPORTANT FOR
COORDINATING INPUTS, SENSORY
INPUTS THAT COME IN AND OUTPUTS,
HOW WE RESPOND TO THOSE TYPES OF
OUTPUTS.
WE ARE TRYING TO IDENTIFY WHICH
PARTS OF THE BRAIN ARE IMPORTANT
FOR COORDINATING THAT
INFORMATION.
THIS IS ABFMRI STUDY, THESE
BRAIN REGIONS WERE ACTIVE WITH
ANY TASK YOU DO.
WE THOUGHT THIS WAS A NETWORK
IMPORTANT FOR THAT FEATURE.
I STOPPED MY INITIATE
EXPERIMENTS AND STARTED TO DO
THESE CONDUCTIVITY EXPERIMENTS
TO SEE IF THESE PARTS OF THE
BRAIN ARE WHAT WE CALLED
FUNCTIONALLY CONNECTED, TALKING
TO EACH OTHER.
THIS PAPER SHOWING FUNCTIONAL
CONNECTIVITY RESULT THAT IS
TRUE, THESE PARTS OF THE BRAIN
WERE TALKING TO EACH OTHER AT
REST NOT ONLY IN TASKS.
THAT TOOK OFF IN MY OWN FORRAY
TO UNDERSTAND BRAIN
ORGANIZATION.
I WAS A BRIGHT EYED AND BUSHY
TAILED GRADUATE STUDENT AT THE
TIME.
I REALIZED IF I WANTED TO
UNDERSTAND THIS SYSTEM HERE WITH
THIS SEED REGION HERE, I COULD
DO THAT WITH A REGION OVER HERE
OR HERE, I COULD DO IT ALMOST
ANYWHERE.
THAT IS EXACTLY WHAT WE DID.
WE HAD BRAIN MAPS OF EVERYTHING
ALL OVER THE LAB, REALLY UP SET
FOLKS SITTING AROUND US.
WE NEEDED TO FIGURE OUT HOW TO
CONDENSE THAT INFORMATION.
WE APPLIED ALL THESE MAPS TO
GRAPH SERIES.
OLAF SPORNS, CALLED THE
ORGANIZATION DEVELOPMENT OF
COMPLEX BRAIN NETWORKS.
THE IDEA OF GRAPH THEORY.
GRAPH THEORY IS SIMPLY DESCRIBES
A SET OF NODES, THAT NODES CAN
BE ANYTHING FROM PEOPLE TO
LOCATIONS OR WEBPAGES THAT ARE
LINKED BY SOME LINE OR EDGE.
THAT WOULD BE LIKE FRIENDS
BETWEEN PEOPLE, ROADS BETWEEN
CITIES OR LOCATIONS OR LINKING
BETWEEN WEBPAGES.
AND THERE'S LOTS OF DIFFERENT
TYPES OF MEASURES THAT COME OUT
OF THIS TYPE OF MATHEMATICS, BUT
ONE THAT IS REALLY STAYED TRUE
IS THE IDEA OF NETWORKS OR
MODULES WHERE WE TRY TO IDENTIFY
SPECIFIC LOCATIONS IN THE BRAIN
THAT ARE MORE HIGHLY CONNECTED
WITH EACH OTHER THAN OTHER
PARTS.
THERE IS MORE INTRACOMMUNITY
EDGES WITH ONE SPECIFIC -- THESE
REGIONS IN THE BRAIN RELATIVE TO
THE INTERCOMMUNITY EDGES WITH
OTHER REGIONS OF THE BRAIN.
THIS WORKED OVER TIME, OVER THE
COURSE OF THE LAST DECADE AND A
HALF HAVE LED TO MANY
FUNDAMENTAL PROPERTIES OF BRAIN
ORGANIZATION, THAT HAS TAUGHT US
HOW THE BRAIN IS ORGANIZED AND
RELATED TO BRAIN CONDITIONS AND
NEUROLOGICAL DISORDERS.
AND THOUGHTS AROUND THE CLINICAL
UTILITY AND APPLIED REVOLUTION
OF FMRI, DURING THIS PERIOD OF
TIME, USING NEW TEAK --
TECHNIQUES RIVALED GENERAL FMRI.
IT HASN'T GOTTEN THERE AND THIS
SHIFT HOW WE CONNECT STUDIES TO
RESTING STUDIES AND STRAIGHT
CHARACTER STUDIES FROM THE MORE
TRADITIONAL PSYCHOLOGICAL
DESTINATIONS SHIFTED THE TYPES
OF QUESTIONS WE WERE ASKING
BECAUSE OF THE EASE OF USE WITH
WHICH WE COULD ACQUIRE THE DATA.
A POTENTIAL ISSUE OVER THAT TIME
IS THE STUDY DESIG
CHA
CHANGED.
ALONG THE WAY OVER THE COURSE OF
FIVE OR SIX OR SEVEN YEARS AS
RESTING STATE FUNCTIONAL
ACTIVITY AND NETWORK NEURAL
SCIENCE HAS EXPANDED TO
UNDERSTAND BRAIN ORGANIZATION
AND DEVELOPMENT, THE DATASETS WE
ARE USING TO STUDY THIS STUFF IS
CHANGING IN SAMPLE SIZE OR
COLLECTION FROM A PRODUCT.
THE PROJECT, THE ABCD STUDY,
SEVEN YEARS AGO, 10,000 PEOPLE,
THE SAMPLE SIZES ARE INCREASING
ENORMOUSLY.
WE ARE STARTING TO SEE A LOT
MORE DATA INSTEAD OF SAMPLE SIZE
INCREASE, THE AMOUNT OF DATA ON
PER SUBJECT BASIS INCREASING
QUITE A BIT.
THE MY CONNECTOME PROJECT FROM
WASHINGTON UNIVERSITY WITH MY
FRIENDS AND COLLEAGUES THERE,
LOTS OF DATA WITHIN PARTICIPANTS
HAS BEEN GROWING QUITE A BIT.
ALONG THAT SAME TIME WE STARTED
SEEING SIGNS OF FAILURES AND
REPRODUCEABILITY HAVE BECOME
MORE APPARENT.
PAPERS ARE LEAKING OUT THAT NOT
PRODUCING IN SUBSEQUENT DATASETS
OR STUDIES, IT IS MORE APPARENT
IT IS COMING ALONGSIDE THESE
CHANGES IN OUR SAMPLE SIZE IN
THE ERA OF BIG DATA.
SO THE FIELD CONTINUES TO EVOLVE
AS DATA ARE COLLECTED IN BROADER
POPULATIONS AND AT A FASTER RATE
THAN EVER BEFORE.
NETWORK NEUROSCIENCE EXISTING OF
MULTIPLE SYSTEMS TO WITH COMPLEX
BEHAVIOR HAS ADVANCED THE FIELD.
HOWEVER, THE ARRIVAL OF LARGE
DATASETS AND REPEATED SAMPLING
DATASETS ARE HIGHLIGHTS
IMPORTANT LESSONS WITH REGARD TO
HOW WE SHOULD DESIGN EXPERIMENTS
TO MAXIMIZE IMPACT ON DISCOVERY
AND APPLICATIONS AND APPLIED IN
CLINICAL SCIENCES.
I GET TO DESCRIBE THAT NOW.
# THIS IS, ALL THIS IS BEING
DESCRIBED AS ABCD STUDY, A STUDY
OF 10,000 ADOLESCENTS.
WHO WE STARTED SCANNING 9 OR 10
YEARS OLD.
WE FOLLOW THEM FOR NOW ABOUT
FIVE YEARS OVER THE COURSE OF 10
YEARS.
ACROSS A POPULATION-BASE SAMPLE
ACROSS THE U.S.
WE ARE USING DATA THAT HAVE BEEN
PROVIDED, YOU KNOW, FREELY FOR
THE PUBLIC TO BE USED.
THIS ONE IS BY ONE OF THE NOUS
PROFESSORS AT UNIVERSITY OF
MINNESOTA, ERIC FESCO, TO MAKE
USE OF THIS DATA MUCH EASIER.
-- ERIC FECZKO.
THIS CAME OUT IN NATURE AND HAS
CAUSED A BIG STIR BECAUSE IT IS
TELLING US SOME FUNDAMENTAL
ISSUES WE NEED TO HANDLE TO
MAXIMIZE THE UTILITY OF THESE
TECHNIQUES USING NON-INVASIVE
IMAGING TO ITS FULLEST.
IT WAS THOUGHT UP BY AMAZING
COLLEAGUE SCOTT MAREK AND
BRENDEN TERVO-CLEMMENS AND NICO
DOSENBACH.
THE BASIC QUESTION OF THE STUDY
IS THIS.
WHAT ARE THE EFFECT SIZES OF
BRAIN CORRELATION AND
NEUROIMAGING PROVIDE EXPLANATION
FOR REPLICATION FAILURES WE
MIGHT SEE IN BRAINWIDE
ASSOCIATION STUDY AND IF SO, WHY
IS THAT?
THE STUDY WAS DONE IN A FULL
SAMPLE ALL TYPES OF WAYS.
I'M GOING TO SHOW YOU PRIMARILY
THE BASE RESULTS, 400
PARTICIPANTS AND THE CLEANEST
ASPECT OF THE DATA.
USING FUNCTIONAL IMAGING OR
STRUCTURAL IMAGES, MEASURES OF
PSYCHOPATHOLOGY, THE RESULT IS
VERY CLOSELY THE SAME.
OKAY?
NOW, WHAT I'M SHOWING YOU HERE
IS A DISTRIBUTION OF THE EFFECT
SIZES THAT YOU GET FROM THIS
BIG, LARGE STUDY ON MEASURES OF
PSYCHOPATHOLOGY.
THIS IS DISTRIBUTION.
THESE ARE THE EFFECT SIZES AND
THE ANATOMY POPS UP HERE.
THE POINT HERE NO MATTER,
LOOKING AT NETWORKS OR EDGES OR
SPECIFIC COMPONENTS OF THE DATA
IS YOU CAN SEE THE DISTRIBUTION
OF THE EFFECT SIZE LOOKS TO BE
RELATIVELY SMALL.
THIS IS THE INITIATE
CONDUCTIVITY MEASURE.
THIS LOOKS FOR COGNITIVE
ABILITY, DISTRIBUTION A LITTLE
BIGGER, BUT ABOUT THE SAME.
THIS IS LOOKING AT BRAIN
STRUCTURE WITH THE SAME
MEASURES.
THE LARGEST EFFECT SIZE, IF YOU
HAVE A SAMPLE THIS LARGE IS .16.
THE POINT IS THE EFFECT SIZES
THAT WE ARE SEEING HERE ON THE
RELATIONSHIPS ARE RELATIVELY
SMALL.
NOW, DOES THE RELIANCE ON THIS
TYPICAL NEUROIMAGING SAMPLE
SIZES PROVIDE A REASON WHY YOU
MIGHT SEE IN SOME CASES AN
EXPLANATION OR REPLICATING
PROBLEM IN BWAS.
THE SAMPLING VARIABILITY TELLS
YOU HOW MUCH AN EFFECT SIZE
VARIES BETWEEN DIFFERENT
SAMPLES.
SCOTT LIKES TO SAY IT IS
SOMETHING YOU HAVE DONE IN YOUR
TRADITIONAL EARLY STATISTICS 101
COURSES, BUT IT IS SUBJECTIVELY
BORING, RARELY CONSIDERED, BUT
IS EXTREMELY IMPORTANT NO MATTER
WHAT TYPE OF DATA WE ARE LOOKING
AT.
THIS IS AN EXAMPLE.
THE SAME STUDY THAT USUALLY
PROVIDES THE CASE.
WHAT IF I WAS TRYING TO
UNDERSTAND THE RELATIONSHIP
BETWEEN AGE, IN THIS CASE YOU
CAN SEE 108 TO 130 MONTHS OF AGE
AND HOW TAL SOMEONE IS?
I CAN GO IN THE ABCD STUDY AND
GET A SAMPLE THAT MAY LOOK LIKE
THIS.
YOU SEE A RELATIONSHIP BETWEEN
HEIGHT AND AGE ABOUT .85.
I CAN GO BACK IN AND DO A
DIFFERENT 25 KIDS AND I MIGHT
SEE A SAMPLE LIKE THIS, WHERE
THERE IS ENOUGH VARABILITY WHERE
THE RELATIONSHIP COULD BE 0.
IF I RESAMPLE AND RESAMPLE AND
RESAMPLE OVER AND OVER AND OVER
AGAIN, THIS IS THE DISTRIBUTION
YOU GET EVEN WITH SOMETHING SO
SIMPLE AS HEIGHT AND AGE.
YOU CAN SEE WITH SMALL SAMPLES
YOU CAN GET ALMOST A PERFECT
RELATIONSHIP BETWEEN HEIGHT AND
AGE, BUT YOU ALSO MAY GET A
RELATIONSHIP BETWEEN 0 OR EVEN
NEGATIVE BETWEEN THOSE TWO
VARIABLES.
IT IS ONLY WHEN YOU -- INSTEAD
OF SAMPLING 25 SUBJECTS AT THE
TIME, 500, 1,000 SUBJECTS AT A
TIME YOU GET THE TRUE EFFECT THE
CORRELATION OF ABOUT .5.
INCREASING SAMPLE SIZE IS
DECREASING SAMPLING
VARIABLEABILITY.
IT IS A DIFFERENT SOURCE OF
ERROR WE SEE IN OUR FIELD.
METHODS OF VARABILITY, PREBIAS,
HEAD MOTION AND STUFF LIKE THAT.
WHAT DOES THIS MEAN FOR SMALL
SAMPLE STUDIES?
IT IS PRETTY SIMPLE.
IF I HAVE ONE LAB DOING A STUDY
ON NEUROIMAGING AND STRUCTURE
AND COGNITIVE ABILITY ARE
RELATIVELY SMALL AND THEY DO A
SAMPLE OF 25 PARTICIPANTS, THEY
DO EVERYTHING PERFECTLY RIGHT
AND THEY MIGHT FIND A
RELATIONSHIP THAT IS HIGH,
STRONG AND POSITIVE.
I MIGHT GO WITH MY LAB AND DO
THE EXACT SAME EXPERIMENT, GET A
SAMPLE OF 25 PARTICIPANTS FOR MY
CORD HERE.
I WOULD GET A COMPLETELY
OPPOSITE EFFECT.
THIS IS JUST TO SHOW THAT SAME
SCENARIO COULD HAPPEN ANY WAY
YOU CUT THE DATA.
THIS BY ITSELF IS NOT
NECESSARILY A HUE AMONG GOUS
PROBLEM, BUT BECAUSE OF OUR
CULTURE AND THE WAY WE PUBLISH
FINDINGS, IT TURNS OUT TO BE A
VERY BIG ONE.
THIS IS A DISTRIBUTION, A FIGURE
THAT HIGHLIGHTS THE DISTRIBUTION
FROM 1 MILLION MED VALUES FROM Z
LIFE.
THIS IS THE SAME PICTURE HOW
PEOPLE WERE DESCRIBING IT ON
TWITTER.
BECAUSE OF THE WAY WE PUBLISH
RESULTS ONLY SIGNIFICANT THINGS
GET PUBLISHED AND NOT VALUING
NULL FINDINGS, THE DISTRIBUTION
GETS SKEWED.
THAT MEANS IF PEOPLE ARE ONLY
PUBLISHING THE SIGNIFICANT
RESULTS FROM SMALL SAMPLES, THE
LITERATURE WILL BE RIPE WITH
INFLATED EFFECTS BECAUSE YOU
CAN'T DO A META ANALYSIS WITHOUT
THE NULL TO GET THE TRUE EFFECT
SIZE.
THIS IS A BIG PROBLEM AND PART
OF OUR STRUCTURE AND
INSTITUTIONS FUNCTION THAT ARE
ASSISTING WITH US BEING FOOLED A
LITTLE BIT ON TRUE EFFECT SIZES.
SO THE OBSERVED EFFECT SIZES, IF
YOU ARE GETTING IT RIGHT FROM
THE FIRST TIME CONSORTIA-LEVEL
DATA ARE REQUIRED.
SO DOES THIS PROVIDE IS
EXPLANATION FOR REPLICATION
FAILURES YOU MIGHT SEE IN THE
LITERATURE AND IF SO, WHY?
THE ANSWER IS YES. --
THIS IS NOT AN FMRI STUDY.
IT IS A STUDY DESCRIBING OUR
DATA.
THE SAME FINDINGS HAVE BEEN
FOUND WITH THE BEHAVIORAL DATA
IN SOME OF THESE STUDIES.
ONE OF THE THINGS THIS OFTEN
REMINDS US OF AND WE ARE
LEARNING LESSONS FROM IS
GENETICS.
THIS IS A CRITICAL REVIEW OF
GENETICS FROM ABOUT 10 YEARS
AGO.
I DIDN'T PULL IT OUT BECAUSE IT
WAS THE BEST PAPER AT THE TIME
AT THIS PAPER, BUT IT HAD GOOD
ILLUSTRATIONS THAT DESCRIBE THE
ISSUE THAT GENETICS WAS HAVING
ABOUT OVER A DECADE AGO.
THIS IS A CRITICAL REVIEW OF THE
FIRST 10 YEARS OF CANDIDATE JEAN
BY ENVIRONMENTAL RESEARCH AND
PSYCHIATRY.
THIS IS A SAMPLE SIZE AND THIS
IS POWER AND THE DIFFERENT
COLORS ARE DIFFERENT, YOU KNOW,
MODERATE, LARGE, AND VERY LARGE
EFFECTS.
THE SAMPLE SIZE IS REQUIRED TO
HIT A CERTAIN LEVEL OF POWER.
WHAT YOU CAN SEE HERE IS UNLESS
YOU HAVE EXTREMELY LARGE EFFECT
SIZES, RIGHT, THAT IN THESE
CANDIDATE GENE STUDIES, YOU NEED
THOUSANDS OF PARTICIPANTS TO
HAVE ENOUGH POWER TO SEE A TRUE
EFFECT.
DOWN HERE YOU SEE AT THE TIME
WHAT THE PUBLISHED SAMPLE SIZES,
HIGHLIGHTING THE DISTRIBUTIONS
WAY ON THE END HERE AND LIKELY
NOT LARGE ENOUGH TO GET PROPER
POWER TO SEE TRUE EFFECTS.
WHICH IS LEADING TO SOME
REPLICATION ERRORS THERE.
THIS NEW ERA OF BIG DATA OR SOME
PARTS OF IMAGING AND SMALL
EFFECTS ARE RECALIBRATION OF
EFFECTS AND GROUNDBREAKING
FINDINGS IS ACTUALLY REALLY
IMPORTANT.
NOW, OF COURSE, IN THE GENETICS
WORLD, IN THE GWAS WORLD, THE
WORK DIDN'T STOP, RIGHT?
THE WORK WENT ON AND THE FIELD
GOT VERY CREATIVE ABOUT HOW TO
HANDLE THE RELATIONSHIPS OF SOME
OF OUR GENES AND COMPLEX
BEHAVIORS IN SMALL EFFECTS.
THEY STARTED DOING LOTS OF
MULTIVARIATE
IT IS STARTING TO USE SOME OF
THE LESSONS LEARNED THAT APPLY
TO MIRROR IMAGING.
IN THIS CASE I'M GIVING YOU ONE
BRIEF EXAMPLE OF HOW WE CAN
HIGHLIGHTING HOW WE CAN LEVERAGE
BIG STUDIES LIKE ABCD STUDIES
AND USING A SAMPLE OF ABOUT
480ADHD, GENERATING POLYRISK
SCORES FOR THE POLYGENIC RISK
SCORES AROUND EXECUTIVE FUNCTION
AND MOBILITY.
HAVING AN OPPORTUNITY TO EXPLAIN
COMPLEX BEHAVIORS EVEN IN ADHD
SYMPTOMS WHICH WE ARE SHOWING
HERE.
WHAT IS INTERESTING AND IS
REALLY IMPORTANT, IN ORDER TO
GET EFFECTS, THERE IS LOTS OF
VARIABILITY IN THE BRAIN.
WHAT YOU REALIZE IS SOME OF OUR
THEORIES AROUND SPECIFIC
NETWORKS OR SPECIFIC CIRCUITS
BEING HIGHLY RELATED, THAT WE
ARE SEEING NOW, THAT IN ESSENCE,
DISTRIBUTIONS OF CIRCUITS ACROSS
THE ENTIRE BRAIN THAT SEEM TO BE
MOST HIGHLY CONTRIBUTING TO
DISORDERS LIKE ADHD.
WHICH IS A COMPLETELY NEW TREND
OR NEW DIRECTION AND WAY TO
THINK ABOUT BRAIN ORGANIZE AND
COMPLEX DISORDERS LIKE ADHD.
THERE ARE SOME IMPORTANT THINGS
WE NEED TO NOT DUPLICATING.
WE NEED TO MAKE SURE THEY ARE
MAX MALI INCLUSIVE, WHICH IS
CRITICAL.
WE HAVE ESSENTIALLY LEARNED FROM
THE GENETICS WORLD THAT NOT
BEING MAXIMUM INCLUSIVE CAN LEAD
TO HIGHER OR LOWER PREDICTIONS.
THE ERA OF BIG DATA HAS NOT BEEN
KIND TO THE SHIFTS IN OUR STUDY
DESIGNS AND DEVELOPMENTAL
NEUROSCIENCE AND IMAGING,
BUILDING OFF THE GROWING PAINS
IN GENETICS AND MULTIVARIATE
WAYS TO LOOK AT THE DATA SEEMED
IMPORTANT TO MOVE IN THE
DIRECTION OF POPULATION STUDIES.
THE WORK IS RESOURCE INTENSETIVE
AND CAN'T BE NECESSARILY
CONDUCTED BY ONE GROUP ALONE
WHICH REQUIRES LOTS OF
COLLABORATION, WAYS TO RETHINK
OF HOW WE ARE DOING OUR WORK.
JUST LIKE SOME OF THESE GWAS, IT
IS ENTRY INTO DIRECT CLINICAL
UTILITY IS LIKELY TO TAKE SOMEM
TI
THERE IS MAYBE A SHORTER AVENUE
INTO THAT SPACE WHICH IS REALLY
BEEN A HUGE SHIFT, BIG DATA, FEW
SUBJECTS AND LESSONS LEARNED
APPLICATIONS.
IT IS VAST OR WIDESPREAD.
EVERYONE HAS HAD AN MRI OR KNOW
OF IT IN CLINICAL APPLICATIONS.
THE QUESTION IS HOW DID THAT
HAPPEN AND WHY HASN'T FUNCTIONAL
BRAIN IMAGING FOLLOWED
TRADITIONAL IMAGING?
STRUCTURAL MRI IN INDIVIDUALS
CAN BE USED EFFECTIVELY TO
DETECT VARIATIONS FROM PERSON TO
PERSON, TUMORS, SWELLING,
INFLAMMATION, STROKE, OTHER
AILMENTS.
IT CAN ASSIST IN ADJUSTING
TREATMENT.
THE EFFORT TO COLLECT THE DATA
IS NOT SUPER LOW, BUT IT IS NOT
UNTENABLE, SO IT IS RELATIVELY
LOW IN A PATIENT.
IN MANY CASES SOME SORT OF
INTERVENTION.
NOW, THE MAJORITY OF THE WORK
TRYING TO UNDERSTOOD THE
TOPOLOGY OF THE BRAIN AND
NETWORK ORGANIZATION USING SOME
OF THESE TECHNIQUES LIKE
FUNCTIONAL CONNECTIVE MRI IS
BASED ON THE AVERAGE.
THE SIGNAL TO NOISE IS SO LOW
ALL THE 14 HOURS OF DATA WITH
ONE INDIVIDUAL WHAT IT LOOKED
LIKE IN THIS INDIVIDUAL AND THE
GROUP AVERAGE.
HERE IS A PICTURE BELOW AND WHAT
YOU CAN SEE IS THE PATTERNS, THE
GENERAL PATTERNS YOU SEE IN THE
GROUP STRUCTURE IS MAINTAINED,
OKAY, BUT LOTS OF SPECIFIC
PATTERNS THAT EXIST WITHIN THIS
INDIVIDUAL.
MEANING THERE'S LOTS OF
DEVIATION FROM THE GROUP IN MANY
WAYS.
LOTS OF THESE ISLANDS AND
SPECIFIC CHARACTERISTICS THAT
EXIST IN THIS INDIVIDUAL
RELATIVE TO OTHERS.
NOW, THAT WAS THOUGHT UP BY
ANOTHER EXPERIMENT CALLED THE
MIDNIGHT SCAN CLUB, STARTED BY
OUR OWN STEVE NELSON AT THE
UNIVERSITY OF MINNESOTA AND NICO
DOSENBACH, TO COLLECT FIVE
HOURS, 10 PEOPLE.
IT WAS CALLED THE MIDNIGHT
SCANNING CLUB DATA BECAUSE THEY
WERE VERY POOR AND THE ONLY TIME
THEY COULD GET CHEAP SCANNING IS
MIDNIGHT.
$25 AN HOUR.
SO THEY STARTED SCANNING FOLKS
TO GET FOUR HOURS OF DATA IN THE
MIDDLE OF THE NIGHT SO THEY
COULD AFFORD IT.
THAT IS WHY IT IS CALLED THE
MIDNIGHT SCANNING CLUB.
THIS PAPER HIGHLIGHTED PERSON TO
PERSON TO PERSON THE GENERAL
STRUCTURE IS THERE, THE
SPECIFICS IN BRAIN ORGANIZATION
IS HIGHLY UNIQUE.
NOW, WHAT WE'VE LEARNED FROM
THIS DATA COLLECTION, WE HAVE
HOURS OF DATA ON THIS PERSON IS
THE RELIABILITY AND SIGNAL TO
NOISE IN FUNCTIONAL MRI CAN BE
JUST AS HIGH IN STRUCTURAL MRI
AS WELL.
HERE IS A CASE OF A CHILD OR AN
ADOLESCENT WHO CAME INTO NICO'S
OFFICE WHO IS A STARTING PITCHER
ON HIS BASEBALL TEAM WHO WAS
HAVING SOME HEADACHES AND HAD
TURNED OUT HAD A VERY LARGE
MASSIVE PERINATAL STROKE THE KID
AND THE FAMILY DIDN'T KNOW
EXISTED.
USING THIS TYPE OF IMAGING, YOU
CAN IDENTIFY VERY PRECISELY,
HIGHLY RELIABLE, EXACTLY HOW
ORGANIZATION TO BE A STARTING
PITCHER CAN BE ORGANIZED IN THIS
PARTICULAR CHILD RELATIVE TO
TYPICAL CONTROLS, WHAT MAKES HIS
FUNCTION ACTUALLY FUNCTION THIS
WAY?
IN A WAY THAT IS HIGHLY PRECISE
WITH HIGH --.
NOW YOU HAVE THIS WAY WHERE YOU
CAN KNOCK OFF AT LEAST ONE OF
THESE ISSUES THAT MADE
TRADITIONAL MRI FEASIBLE IN
CLINICAL SETTINGS.
ANOTHER EXPERIMENT, IN THIS CASE
NOW, IN ESSENCE, CASTING AN ARM,
DOING A SPECIFIC INTERVENTION
WITH FMRI, INDUCING SENSORY
DEPRIVATION, AND MOTOR
DEPRIVATION IN THREE INDIVIDUALS
WHERE YOU CAST AN ARM, THEIR
DOMINANT ARM AND YOU DO THAT
CASTING FOR TWO WEEKS.
YOU DO REPEATED SAMPLING OF THE
SCANNING 45 TO 65 TIMES TO GET
ENORMOUS AMOUNTS OF DATA WITH
INDIVIDUALS.
ALL OF A SUDDEN YOU CAN SEE
EXACTLY HOW THE BRAIN IS
REORGANIZING DURING A SPECIFIC
A PERFECT CIRCUIT REQUIRED FOR
IMPROVED TREATMENT IN
DEPRESSION, WITH PRECISION
MAPPING THAT YOU GET IMPROVED,
YOU GET IMPROVED OUTCOMES.
YOU CAN TAILOR YOUR INTERVENTION
TO BE ABLE TO IMPROVE ON THE
TREATMENT AS LONG AS YOU HAVE
THE DATA THAT IS NECESSARY TO
GET THE RIGHT LOCATION FOR THE
TARGETING AS OPPOSED TO WHAT IS
CURRENTLY DONE, WHICH IS JUST
ONE SIZE FITS ALL LOCATION FOR
FOLKS.
NOW YOU HAVE A WAY WHERE YOU CAN
NOW USE THE TECHNIQUE TO ADJUST
TREATMENT.
THE PROBLEM, OF COURSE, IS THE
LAST ONE.
THE EFFORT IS LOW ON COLLECTION
IN THE PATIENT.
RIGHT?
IF YOU NEED TO GET FIVE TO 14
HOURS OF DATA IN A GIVEN PERSON,
YOU -- IT IS GOING TO BE HARD TO
DEPLOY THIS IN A WAY THAT WOULD
BE USEFUL IN A CLINICAL SETTING.
WELL, IN FACT, LIKE I SAID, IN
ORDER TO EVEN GET 90%
RELIABILITY IN THE CASE FROM
SOME OF THESE EARLY PAPERS, WE
NEED UPWARDS OF AN HOUR TO TWO
HOURS OF DATA.
NOW, THERE'S LOTS OF EFFORTS
THAT HAVE BEEN GOING ON HERE,
CONNOR LYNCH'S LAB IS DOING THIS
WORK.
WE ARE TRYING TO WORK TO CHANGE
THE WAY WE COLLECT THE DATA.
THIS IS SOME OF THIS, THIS IS
WORK STARTED OUT OF NIH.
TO REDUCE THE AMOUNT OF TIME
THAT IS REQUIRED TO GET THAT
LEVEL OF RELIABILITY.
EVEN DOWN TO 15 MINUTES OF DATA
COLLECTION.
WE ARE NOW WORKING ON HUMAN
FUNCTIONAL BRAIN NETWORKS MAY
HELP WITH SOME OF THESE ISSUES,
EVEN WHEN YOU DON'T HAVE ACCESS
TO AN MRI.
HERE IS JUST A PICTURE.
200 SUBJECTS FROM THE ABCD
STUDY, APPLYING PRECISION
MAPPING FROM PERSON TO PERSON,
THE SAME TRENDS HOLD.
I PUT A BOX AROUND THE DLPFC,
AROUND THE AREA YOU WOULD WANT
TO TARGET FOR THE TREATMENT
RESISTANT DEPRESSION.
AND HIGHLIGHTING THE VARIABILITY
YOU CAN SEE FROM PERSON TO
PERSON.
BUT IT IS ALSO BECAUSE WE KNOW
THERE ARE SOME CHARACTERISTICS
SIMILAR FROM PERSON TO PERSON,
YOU CAN SEE IT AS WE ARE LOOKING
HERE.
WE MIGHT BE ABLE TO LEVERAGE
THAT TECHNIQUE TO IDENTIFY AT
LEAST A PROBLEM ACCESS
TO MRI YOU WANT TO DO A
TREATMENT IN THIS CASE AND DON'T
HAVE ACCESS TO MRI TO IMPROVE.
THESE HAVE SHOWN HIGHER ABILITY.
THIS IS A COMPARISON OF LOOKING
AT THESE DATA WITH THESE
PROBABLISTIC AND GROUP SETS THAT
ARE HIGHLY COMMON IN THE FIELD.
AND, AGAIN, JUST HIGHLIGHTING
RELATIVE TO THESE COMMON
DATASETS THAT THE RELIABILITY OF
THE FINDINGS INCREASE QUITE A
BIT USING THESE PROBABLISTIC
MAPS AND STUDIES IN THE FIELD.
IN THIS LAST SLIDE I'M GOING TO
SHOW YOU HERE IS JUST, AGAIN,
POINTING OUT THAT FOR, IN THE
CASE OF TREATMENT RESISTANT
DEPRESSION, WE ARE ESSENTIALLY
TRYING TO HIT A CIRCUIT IN AN
INDIVIDUAL THAT TARGETS THE SUB
GENERAL ZONE.
AT LEAST THAT IS ONE OF THE
THEORIES.
AND USING THESE PROBABLISTIC
TARGETS, 10 SUBJECTS ACROSS
ADULTS AND KIDS, SHOWING ABILITY
TO HIT THE SUB GENERAL ZONE
QUITE EASILY WITH THIS
PROBABLISTIC TARGET AND MOVING
SLIGHTLY AWAY FROM THAT TARGET
SHOWS MORE VARIABILITY IN YOUR
ABILITY TO HIT THE PRECISE ZONE.
LOTS OF POTENTIAL FOR USING
THESE TYPES OF TECHNIQUES AND
DATA SOURCES FOR LOW RESOURCE
SETTINGS IN CASES YOU CAN'T
OBTAIN AN MRI.
SO THAT'S THE LAST LITTLE BIT,
WHICH PUTS US ON A REALLY GOOD
FOOTING FOR THE FUTURE.
SO WITH THE RIGHT CONDITIONS,
FMRI, CONDUCTIVITY MRI, CAN BE
HIGHLY RELIABLE IN LARGE SUBJECT
EFF
EFFECTS, STUDIES TO MONITOR
EFFICACY FOR TARGETING CERTAIN
INTERVENTIONS IN THE CASE
EXAMPLES I GAVE WITH
NEUROMODULATION OR DETAILED
ASPECTS OF THE THE
NEUROPHYSIOLOGY ARE OBTAINABLE
IN SMALL SAMPLES AS LONG AS THE
DATA ARE BEING COLLECTED IN THE
RIGHT WAY.
NOW WE UNDERSTAND THE PARAMETERS
ON HOW TO CONDUCT THESE RELIABLE
REPLICATING STUDIES, WE WILL
MASSIVELY CELEBRATE
SIGNIFICANTLY IN THE NEXT DECADE
AS LONG AS WE ARE THINKING, ALL
OF OUR INSTITUTIONS, INCLUDING
THE SCIENTISTS, THE FUNDERS, THE
JOURNAL EDITORS, THAT WE ARE ALL
THINKING ABOUT THIS STUFF IN THE
RIGHT WAY.
THERE IS A REALLY NICE PAPER BY
KATARINA GRATTON, STEVE NELSON,
GORDON ON THESE DIFFERENT ROADS
TO TAKE TO DO HIGHLY RELIABLE
SUCCESSFUL STUDIES.
FOR FOLKS WHO DO MRIs, I WOULD
SUGGEST THE READ.
AT THE END, I'M GOING TO GO OVER
SOMETHING THAT DOES USUALLY LEAD
TO INTERESTING DISCUSSION.
ONE OF THE THINGS WE DO IN THE
BUSINESS WORLD.
O
I'M NOT IN THE BUSINESS WORLD,
BUT I FOLLOW AND PLAY ONE ON TV.
STRENGTHS, WEAKNESSES,
OPPORTUNITIES AND THREATS TO
SMAK SURE YOU HAVE OPTIMAL
STRATEGY FOR STRATEGIC PLAN.
IT IS VERY COMMON.
YOU LEARN IN BUSINESS SCHOOL
101.
WE DON'T TYPICALLY DO THAT IN
OUR OWN FIELD SO ONE OF THE
THINGS I HAVE DONE, WE RECENTLY
PUBLISHED IN ANNUAL REVIEWS IS
DO A SWAT ANALYSIS IN COGNITIVE
NEUROSCIENCE AND SCIENCE IN
GENERAL TO HELP THINK
STRATEGICALLY ABOUT WHAT WE,
WHAT ARE OUR STRENGTHS, WHAT ARE
OUR WEAKNESSES?
WHAT ARE THE THREATS THAT
PREVENT TRUE PROGRESS AND
OPPORTUNITIES WE NEED TO TAKE
CARE OF.
WE MIGHT WANT TO TAKE ON.
SO I'M GOING TO DO THAT LITTLE
EXERCISE.
IT IS NOT THE FULL THING, BUT
YOU WILL GET A SENSE OF WHAT
SOME OF THOSE THINGS ARE AND
WITH THE GROUP HERE AND WHAT THE
FIELD NEEDS TO THINK THROUGH.
SO STRENGTHS.
SO ONE IS THAT WE, PARTICULARLY
IN OUR FIELD, THERE IS A GROWING
NUMBER OF SCIENTIFIC DISCIPLINES
IN OUR FIELD.
WE HAVE NEW ACCESS TO BIG DATA
RESOURCES AND DATA AND CODE AND
REALLY A LOT OF INFRASTRUCTURE
ON COMPUTING HAS BEEN DEVELOPED
THAT MAKE A LOT OF THE WORK I'M
TALKING ABOUT TODAY POSSIBLE AT
ALL.
THERE IS A TON OF CROSS SPECIES
WORK TO BRIDGE FINDINGS,
INDIRECT MEASURE OF NEUROBIOLOGY
AND THE CIRCUITS DIRECTLY TO THE
NEUROBIOLOGY THAT EXISTS.
WE HAVE A LOT OF PUBLIC-PRIVATE
PARTNERSHIPS AND NON-PROFIT
ORGANIZATIONS UNDERSTANDING THE
IMPORTANCE OF NEUROSCIENCE FOR
OUR EVERYDAY LIVES.
AND WE HAVE A LOT OF JUNIOR
INVESTIGATORS WHO APPEAR TO BE
OPEN TO ENTERTAINING THE
WEAKNESSES AND THREATS TO OUR
FIELD THAT IS EXTREMELY
IMPORTANT FOR OUR FUTURE.
OKAY.
SO HOW ABOUT SOME OF THE
WEAKNESSES?
THERE'S ALWAYS ISSUES, AND I
THINK THIS IS WITH EVERY FIELD
DEPENDING WHERE YOU ARE AT, IN
PARTICULARLY IN COGNITIVE
NEUROSCIENCE AND BEHAVIOR AND
PSYCHOLOGY, THERE IS OFTENTIMES
ISSUES OF DATA QUALITY THAT
CONTINUE TO MUTE SOME PROGRESS.
WE NEED TO CONTINUE TO GET
BETTER AT THAT.
A BROADENING OF EXPERTISE AND
DISCIPLINES IS GREAT FOR
COGNITIVE NEUROSCIENCE FOLKS
LIKE ME, BUT MOVES THE FIELD
AWAY FROM GROUNDING IN
NEUROSCIENCE.
IT IS IMPORTANT WE MAINTAIN
THAT.
EFFECT SIZES SOMETIMES ARE SMALL
WHEN EXAMINING COMPLEX
BEHAVIORS.
IT IS WHAT IT IS?
HOW DO YOU HANDLE THAT?
WHAT DOES IT MEAN?
MANY OF OUR MEASURES ARE NOISY,
THEY ARE A LOW SIGNAL.
GENERAL WEAKNESSES EXIST IN OUR
SPACE.
WHAT ARE SOME OF THE THREATS?
WE ARE SEEING SOME THREATS THAT
WE IGNORE THE WEAKNESSES AND
CARRY ON THE WAY WE HAVE ALWAYS
DONE THINGS.
THERE IS A LACK OF UNDERSTANDING
OF HETEROGENEITY PROBLEM.
I HIGHLIGHTED THIS BRIEFLY, WE
HAVE A PROBLEM REPORTING IN THE
LABS BECAUSE WE NEED TO PUBLISH
THINGS QUICKLY AND HAVE
SIGNIFICANT VALUE WE TRY TO KEEP
RUNNING EXPERIMENTS UNTIL WE
FIND THAT.
'-HACKING.
A LOT OF TIMES THE ONLY THING
ACCEPTED ARE HIGHLY SIGNIFICANT
IN THE LITERATURE WHICH LEADS TO
THE SKEWS WE ARE SEEING.
OUR ACADEMIC INFRASTRUCTURE
REWARDS SELECTIVE REPORTING.
ONLY POSITIVE FINDINGS ARE
TYPICALLY ACCEPTED IN MOST CITED
JOURNALS.
THAT IS WHAT WE WANT TO SEE IN
OUR PRELIMINARY STUDIES, THIS IS
HIGH P-VALUES TO FEED INTO THE
CULTURE.
THE FUNDING MECHANISMS ARE NOT
SET UP TO OPTIMIZE STUDY
DESIGNS.
SET UP ACROSS LABS IS SOMETIMES
EXTREMELY IMPORTANT THAN AN
INDIVIDUAL LAB DOING ONE STUDY
ALONE.
MECHANISMS -- I MEAN, IT ALREADY
EXISTS BUT INCREASING MECHANISMS
THAT REWARD LOTS OF
COLLABORATION ACROSS SPECIFIC
STUDIES IS IMPORTANT.
OUR ACADEMIC ACHIEVEMENT CULL
CULTURE.
PROMOTION IS NOT NECESSARILY SET
UP TO HANDLE WHAT WE ARE
LEARNING AND HOW TO CONDUCT THE
SCIENCE.
WE TALK ABOUT THIS OFTEN.
EVEN IN MY OWN EXPERIENCE, YOU
KNOW, MY ABILITY TO COLLABORATE
AS A YOUNG INVESTIGATOR WITH
SENIOR FOLK WAS A NEGATIVE, AS
PART OF MY PROMOTION, GETTING
P
PROMOTED MY FIRST TIME.
BECAUSE I WAS NOT DOING
EVERYTHING ALL BY MYSELF I WAS
BRINGING TOGETHER THESE LARGE
GROUPS TO DO BIG STUFF, THAT WAS
A NOT IN MY PROMOTION CULTURE,
MY ABILITY TO GET PROMOTED.
A LOT OF FOLKS -- I VALUE THE
DIVERSITY IN MY OWN LAB AND MY
OWN WORK AND MY OWN STAFF
BECAUSE I THINK THAT VARIABILITY
DRIVES THAT, THAT DOESN'T EXIST
SO WE ARE REWARDED.
WE END UP FALLING INTO THE SAME
CULTURE AND LEAD TO MISLEADING
FINDINGS AND NOT MAXIMIZE OUR
POTENTIAL.
OUR TRAINING ENVIRONMENTS ARE
NOT NECESSARILY EQUIPPED TO
HANDLE THIS DATA.
IT IS SUPER COMPLEX AND WHILE WE
ARE GOOD AT TRAINING BASE
KNOWLEDGE IN THE FIELDS WE ARE
IN, THE CROSS DISCIPLINE
KNOWLEDGE IS A LOT HARDER AND
NOT NECESSARILY SET UP FOR
TODAY'S WORLD.
I ALREADY HIGHLIGHTED SOME OF
THE LACK OF DIVERSITY IN SUBJECT
POPULATIONS AND IN
INVESTIGATORS.
LAST THING IS THERE'S JUST AN
ENORMOUS AMOUNT OF OPPORTUNITY
RIGHT NOW.
LIKE THIS IS THE TIME, RIGHT?
THERE IS AN OPPORTUNITY TO
EXPAND OUR ENTHUSIASM FOR THE
TYPE OF SCIENCE, THESE NEW
APPROACHES TO IMPROVE SNR AND
GET SCIENCE THAT CAN REALLY
CHANGE OUR WORLD.
NOW WE ARE THERE.
WE UNDERSTAND HOW TO DO IT.
OPEN SCIENCE DATA SHARING OR
RESOURCE SHARING.
THERE IS AN OPPORTUNITY, THE
INFRASTRUCTURE IS THERE, IF WE
CAN CHANGE OUR CULTURE TO BE
MORE OPEN WITH OUR DATA AND
SCIENCE, IT CAN TAKE US A LONG
WAY.
OPPORTUNITY TO GROW AND SUPPORT
AND MOTIVATION OF A DIVERSE WORK
FORCE FOR A NEW ERA.
THERE'S CLEARLY A MOVE RIGHT NOW
TO IMPROVE DE.I. IN OUR
INSTITUTIONS.
ENTHUSIASM IS ALLOWING THE
GROWTH OF BIG DATA RESOURCES.
POST PEAK, MORE OUTREACH TO
MOBILE TECHNOLOGIES AND WE HAVE
AN OPPORTUNITY TO LEVERAGE, WHAT
I CAN SEE IS JUST AN INCREDIBLE
BATCH OF JUNIOR SCIENTISTS WHO
COULD REALLY, REALLY BEND THE
CURVE IF WE TAKE THE ISSUES AND
OPPORTUNITIES I HAVE BEEN
HIGHLIGHTING TODAY SERIOUSLY.
I'M GOING TO END THERE.
I WANT TO THANK YOU ALL FOR
HAVING ME.
I ENJOYED THE OPPORTUNITY TO
GIVE THIS PARTICULAR LECTURE.
HERE IS A QUICK SNAPSHOT OF MY
LAB AND THE FOLKS INVOLVED WITH
THE WORK.
AND OF COURSE TO ALL THE FUNDING
THAT HAS COME MY WAY TO BE ABLE
TO DO THE SCIENCE THAT EXCITES
ME AND ALLOWS ME TO DO THE WORK
THAT I JUST REALLY LOVE TO DO.
I APPRECIATE IT AND THANK YOU
VERY MUCH.
>> THANK YOU, DR. FAIR.
WHAT A WONDERFUL TALK.
THE QUESTIONS ARE STREAMING IN.
BEFORE I GET TO THEM, I WANT TO
REPEAT THE CONTINUING MEDICAL
EDUCATION CODE SO THAT CODE IS
37949.
SO SOME OF THE FIRST QUESTIONS
THAT CAME IN ARE REALLY TRYING
TO DIG IN AND EXPLAIN THE
VARABILITY.
I THINK YOU TOUCHED ON SOME OF
THIS BUT MAYBE YOU CAN OFFER
FURTHER REFLECTION.
A TWO-PART QUESTION.
IS THE SAMPLING VARABILITY
REFLECTED NATURAL HETEROGENITY
AND SPECIFIC TO FMRI AND CAN THE
DIFFERENCES BE EXPLAINED BY
DIFFERENT FMRI APPROACHES IN
DIFFERENT LABS?
>> THE ANSWER TO ALL OF THAT IS
YES.
IT IS REFLECTING SOME HET
HETEROGENEITY.
WE ARE TRYING TO GET HOMOGENEOUS
SAMPLES SO THAT IS LIKELY PART
OF IT.
HOW MUCH?
WE DON'T KNOW.
WHAT WAS THE SECOND QUESTION
AGAIN?
>> IS SOME OF IT EXPLAINED IN
DIFFERENCES IN APPROACH BETWEEN
LABS, MEASUREMENT DIFFERENCES
>> ABSOLUTELY LIKELY TO BE SOME
APPROACH BETWEEN LABS, BUT THE
BULK, NO.
CERTAINLY YOU ARE GOING TO, IN
FACT, I SAID WE DID THIS IN A
MILLION WAYS, DIFFERENT
APPROACHES FROM OTHER LABS, DATA
PROCESSES FROM OTHER PLACES IS
THAT THERE'S -- THERE IS
ABSOLUTELY -- I DID TOUCH ON
THIS, ABSOLUTELY OPPORTUNITIES
TO INCREASE THE EFFECT SIZES AND
WHAT NOT OF WHAT I SHOWED TODAY.
HOW MUCH IS NOT CLEAR, BUT
LIKELY TO BE MARGINAL UNTIL WE
TACKLE THE HETEROGENEITY FINDING
OR MASSIVE FINDING.
A LOT OF TIMES THESE
RELATIONSHIPS ARE REALLY
COMPLEX, TO DEFINE A CIRCUIT OR
A THING OR THE REGION THAT WILL
EXPLAIN SO MUCH VARIANCE IS
UNLIKELY.
SO IT IS SOME, BUT NOT PROBABLY
ALL.
THE LAST QUESTION WAS REAL
QUICK, I DON'T WANT TO GET IT
WRONG.
>> YOU GOT THE TWO PARTS.
>> OKAY.
>> SO WE'LL GO ON TO THE NEXT
QUESTION.
THE NEXT QUESTION IS DO YOU HAVE
ANY ADVICE FOR THE NIH ABOUT HOW
TO ADVANCE REPRODUCEABLE SCIENCE
AND NEUROIMAGING.
THE EXAMPLE IS SHOULD
PREREGISTRATION BE ENCOURAGED OR
REQUIRED FOR THESE STUDIES?
>> IT IS FUNDY, I GOT THIS
QUESTION -- I DID THE NIMH
LECTURE WITH JOSH GORDON.
I SAID YOU NEED TO GIVE US MORE
MONEY, JOSH.
NO, DO THINK -- I PERSONALLY
THINK THERE NEEDS TO BE A
RETHINK IN HOW WE EMPHASIZE THE
WAY THAT WE ARE CONDUCTING
STUDIES AND A CRITICAL REVIEW OF
WHAT ARE THE BEST DESIGNS FOR
SPECIFIC MECHANISMS, YOU KNOW?
THAT IS THE HARD PART.
THAT DOESN'T MEAN YOU CAN'T DO
SMALL STUDIES.
THIS IS A FIELD THAT SHIFTED SO
FAR INTO THIS ONE DOMAIN IN THE
WAY WE CONDUCT STUDIES, IT HAS
TAKEN AWAY THE THINGS THAT FIT
NICELY WITH TRADITIONAL RO1s AND
IGNORING THE THINGS THAT WOULD
BE BETTER AND MORE COLLABORATIVE
STUDIES PREREGISTRATION IS A
GREAT IDEA TO SOME EXTENT.
I THINK -- I TALK ABOUT THIS ALL
THE TIME.
EVEN IF YOU DO A SMALL STUDY, IT
NEEDS TO BE -- YOU NEED TO
PUBLISH ALL OF IT.
WE NEED TO BE ABLE TO VALUE NULL
FINDINGS.
THAT IS THE PROBLEM.
WE DON'T VALUE IT AS BEING
ACADEMIC.
SOME PEOPLE WON'T PUBLISH IT.
IF PEOPLE DON'T PUBLISH IT THEN
YOU GET THESE INFLATED EFFECTS,
RIGHT?
SO IT IS A COMPLETE CHANGE IN
CULTURE AND HOW WE VALUE THE
WORK, RIGHT?
AND THEN HOW WE GO ABOUT IT.
LIKE I SAID EARLIER, IF IT IS
THE CASE WE VALUED NULL FINDINGS
EQUALLY TO SOMETHING
SIGNIFICANT, WE WOULDN'T BE IN
HERE.
WE WOULD BE ABLE TO DO OUR META
ANALYSIS AND GET THE RIGHT
EFFECT AND KNOW WHAT IT IS.
IT IS NOT HOW WE ARE SET UP.
PREREGISTERED REPORTS ARE NICE
BECAUSE THEY DO ALLOW A LITTLE
BIT OF THAT FLEXIBILITY.
SO I DO THINK THAT IS PART OF
THE SOLUTION, PROBABLY NOT ALL
OF IT.
#
>> SO THE NEXT QUESTION IS
MOVING KIND OF AWAY FROM THE
SCIENCE OF SCIENCE DOWN TO SOME
MORE SPECIFICS.
SO IT IS I'M CURIOUS ABOUT
WHETHER YOU CAN TELL FROM YOUR
IMAGING WHETHER AUTISM AND ADHD
IS A MATTER OF GENETICS, EPI
GENETICS OR SOMETHING IN
BETWEEN?
>> YES.
YOU KNOW, THE -- IN FACT, WE
HAVE ONGOING, PRECISION MAPPING
STUDIES IN BOTH ADHD AND AUTISM,
CONNECTING A LOT OF GENETICS.
THE DATA SEEMED TO SUGGEST IN
SOME CASES IT IS VERY HEAVILY
LEANED ON THE GENETICS, IT IS
VERY CLEAR PARTICULARLY FROM THE
RARE VARIANCE STUDIES IN ADHD
AND IN AUTISM.
MORE IN AUTISM THAN ADHD.
THEY ARE HIGHLY RELATED SO THERE
ARE LOTS OF THESE FINDINGS,
UPWARDS OF THE FOLKS HAVE ADHD
AS WELL, NOT NECESSARILY VICE
VERSA.
IT IS BECAUSE THE DISEASE IS SO
HETEROGENEOUS, THE BEHAVIORAL
PHENOTYPE LOOKS THE SAME,
REGIONS IN THE BRAIN ARE
DIFFERENT AND SOME WILL INCLUDE
MORE ENVIRONMENTAL FACTORS AND
LESS RELIANCE ON GENETICS.
SO THAT HAS TO BE NOT KNOWN FOR
SURE YET BUT CERTAINLY BEING
INVESTIGATED.
>> THANKS.
I KNOW WE ARE BUMPING UP AGAINST
TIME BUT ANOTHER QUESTION IS
MANY THREAT IDENTIFIED ARE NOT
UNIQUE TO NEUROSCIENCE.
>> THAT'S RIGHT.
>> ARE THERE ANY AFFECTS
PARTICULARLY CHALLENGING FOR THE
NEUROSCIENCE COMMUNITY THAT
SHOULD HAVE A SPECIAL ATTENTION
THAT IS DIFFERENT IN OTHER AREAS
WHERE WE ARE GRAPPLING WITH ALL
THESE ISSUES?
>> YEAH, I DO.
THAT IS KIND OF A LITTLE BIT BY
DESIGN.
THE SAME THINGS WE ARE DEALING
WITH IN THE COGNITIVE
NEUROSCIENCES ARE NOT UNIQUE.
THIS IS NOT AN FMRI STUDY, I
REPEAT.
IT IS NOT UNIQUE.
YOU CAN SEE IT RAMPANT THROUGH
ALL OF OUR WORK, RIGHT?
IF YOU WANT TO ACCELERATE
MAXIMUM POTENTIAL YOU HAVE TO
CHANGE SOME THINGS.
I THINK TO BE HONEST, I TALKED
ABOUT IT, I WAS ABLE TO DO ONE
QUOTE FROM WHEN I WON THE
MacARTHUR AWARD A YEAR AND A
HALF AGO.
I THINK ONE OF THE BIGGEST
CHALLENGES I CAN SEE IS
DIVERSIFYING OUR WORKFORCE.
I THINK IT IS A HUGE MISSED
OPPORTUNITY.
A LOT OF THINGS WE HAVE SEEN
HERE WOULD HAVE BEEN DISCOVERED
A LONG TIME AGO IF WE HAD
DIFFERENT VOICES IN THE MIX.
VARIABILITY IS FUNDAMENTAL
PROGRESS, BUT WE DON'T VALUE
THAT AS WE DO WITH OTHER THINGS
LIKE HOW IMPORTANT IT IS FOR
ACTUALLY MAXIMIZING DISCOVERY.
THAT IS A BIG BOTTLENECK, A HUGE
ONE THAT IS VERY DIFFICULT TO
OVERCOME.
BUT WE NEED TO DO BETTER.
I DO THINK THAT OUR -- THE
SPECIFIC ASPECTS OF OUR CULTURE,
I MEAN, IF YOU THINK ABOUT THE
BASICS OF PROMOTION AND OUR --
THERE ARE SOME CHANGES IN WHAT
WE, AS KIND OF WHAT GETS IN THE
HIGH-PROFILE JOURNAL AND WHAT
DOESN'T AND THINGS LIKE THAT,
THOSE ASPECTS, WHAT GETS FUNDED,
HOW PEOPLE ARE REVIEWING THINGS.
EVEN IF YOU, IN MANY CASES,
BASED ON WHAT I JUST SHOWED YOU,
IF YOU START -- IF YOU DO A
BUNCH OF PRELIMINARY DATA WITH
SMALL SAMPLES AND ONLY SEE
HIGHLY SIGNIFICANT THINGS IT
ALMOST HAS TO BE WRONG.
IF IT IS UNDERPOWERED, IT CAN'T
BE RIGHT.
SO BUT THAT IS NOT HOW WE REVIEW
THE LITERATURE.
THAT IS NOT HOW WE REVIEW THE
GRANTS.
THESE ASPECTS OF OUR CULTURE
THAT FEED INTO THE BASIC,
RELATIVELY BASIC STATISTICS WE
ALL LEARNED IN OUR EARLY CLASSES
NEED TO CHANGE.
I THINK ON THE PROMOTION FRONT
IS MOVING PAST THE TRADITIONAL,
YOU KNOW, AGAIN, ALL ABOUT
INCENTIVES.
WHAT ARE THE INCENTIVES?
I THINK THERE ARE SOME THINGS WE
HAVE HAD TO STRUCTURE FOR
TEACHING SERVICE AND ACADEMY IN
OUR PROMOTION STRUCTURE DECADES
UPON DECADES UPON DECADES.
THERE ARE NEW THINGS WE NEED TO
CHANGE THAT CHANGE SOME OF THE
UNDERLYING ISSUES THAT ARE
SLOWING US DOWN A LITTLE BIT.
>> THANK YOU.
I KNOW WE ARE OVER TIME, BUT WE
REALLY APPRECIATE YOUR BEING
WITH US THIS OFTEN AND YOUR
THOUGHT-PROVOKING TALK.
AND I THINK THE LAST ANSWER IS A
GREAT ONE TO END ON BECAUSE IT
GIVES GREAT FOOD FOR THOUGHT.