WELL, GOOD AFTERNOON,
EVERYONE.
I'M NOT NINA SCHOR, AS YOU CAN
TELL.
SHE SENDS REGRETS, NOT ABLE TO
INTRODUCE TODAY'S SPEAKERS.
I'M DAVID SHURTLEFF.
IT'S MY GREAT HONOR AND PLEASURE
TO INTRODUCE ONE OF OUR OWN, DR.
LAUREN ATLAS, A YEAR TWO WEEKS
AGO, A GREAT ACCOMPLISHMENT,
WE'RE SO PROUD OF HER, ALL SHE'S
BRINGING TO OUR PROGRAM.
BACKGROUND, DR. ATLAS IS AN
EXPERIMENTAL PSYCHOLOGIST, AND
AFFECTIVE NEUROSCIENTIST
RECENTLY TENURED SENIOR
INVESTIGATOR, AND CHIEF OF NCCIH
EFFECTIVE NEUROSCIENCE AND PAIN
LABORATORY.
SHE ALSO AS JOINT POINT WITH
NIDA, NIMH, AND UNIVERSITY OF
MARYLAND, BACHELOR OF ARTS IN
PSYCHOLOGY UNIVERSITY OF CHICAGO
IN 2003, Ph.D. IN PSYCHOLOGY
FROM COLUMBIA UNIVERSITY IN
2011.
COMPLETED A POSTDOC AT NYU
DEPARTMENT OF PSYCHOLOGY.
2024 DR. ATLAS JOINED US HERE AT
NCCIH.
AT THAT TIME WE WERE A BRAND-NEW
INTRAMURAL PROGRAM, JUST FORMED
IN 2012.
SHE CAME TWO YEARS LATER.
WHEN SHE ARRIVED SHE LAUNCHED A
SECTION ON AFFECTIVE
NEUROSCIENCE AND PAIN, THROUGH
HER RESEARCH COMBINES EXPERTISE
IN PAIN RESEARCH HOW
PSYCHOLOGICAL FACTORS SHAPE
PAIN, EMOTIONAL FACTOR.
I'M A PSYCHOLOGIST TOO, IT
BRINGS SO MUCH RICH INFORMATION
AND INSIGHT INTO A DISORDER SUCH
AS PAIN BECAUSE IT'S MORE THAN
KNOWS NOCICEPTION.
SHE AND HER TIME COMBINE
ADVANCED fMRI ANALYSIS WITH
EXPERIMENT DESIGN TO EVALUATE
EXPECTATION AND SOCIAL FACTORS,
PUBLISHING 55 FACTORS SINCE SHE
JOINED THE NIH, AND HER TRAINEES
HAVE DONE GREAT THINGS INCLUDING
FACULTY POSITIONS AND PROGRAM
OFFICERS IN FACT HERE AT THE
NIH.
DR. ATLAS HAS HELD NUMEROUS
EDITORIAL AND LEADERSHIP
POSITIONS IN THE PAIN RESEARCH
AND AFFECTIVE NEUROSCIENCE
COMMUNITIES, CO-CHAIR OF UNITED
STATES ASSOCIATION FOR STUDY OF
PAIN, NEUROIMAGING SPECIAL
INTEREST GROUP, AND FINALLY DR.
ATLAS IS AN ENTHUSIASTIC AND
ACTIVE MEMBER OF THE NIH
INTRAMURAL RESEARCH COMMUNITY
WITH SERVICE AND LEADERSHIP
ROLES IN IN ADVISORY GROUPS ACS
THE NIH.
JOIN ME IN WELCOMING DR. ATLAS
TO THE PODIUM FOR THIS NIH
DIRECTOR'S LECTURE.
THANK YOU.
[APPLAUSE]
>> THANKS SO MUCH, DAVID, FOR
THE WARM INTRODUCTION.
SO NICE TO ACTUALLY SEE PEOPLE
IN PERSON.
I WAS CONFIDENT WITH THE WEATHER
THAT WE'D HAVE A VERY EMPTY ROOM
BUT IT'S REALLY NICE SO MANY
PEOPLE CAME OUT.
TODAY I'LL BE TALKING ABOUT OUR
WORK OVER THE PAST TEN YEARS ON
NEURAL AND PSYCHOLOGICAL
INFLUENCES ON PAIN AND ITS
ASSESSMENT.
I WANT TO REALLY ACKNOWLEDGE ALL
OF THE TRAINEES I'VE HAD THE
BENEFIT OF WORKING WITH.
I WORKED WITH STELLAR
ENTHUSIASTIC, BRILLIANT, AND
KIND PEOPLE.
IT'S BEEN A PLEASURE TO BOTH
CONTRIBUTE TO YOUR GROWTH AS
TRAINEES, ALSO TO GROW MYSELF
THROUGH THE YEARS AND CHAPTERS.
THE MISSION, TO UNDERSTAND HOW
PSYCHOLOGICAL FACTORS SHAPE
PAIN.
IN AMERICA MORE THAN 30% OF
AMERICANS ARE LIVING WITH SOME
FORM OF CHRONIC OR SEVERE PAIN,
OVER 7% REPORT DEBILITATING
PAIN, MORE PEOPLE LIVE WITH
CHRONIC PAIN THAN CANCER, HEART
DISEASE, DIABETES COMBINED.
WE ALSO SEE THAT PAIN IS AT THE
INTERSECTION OF MULTIPLE
DIFFERENT URGENT HEALTH CRISES
IN AMERICA.
WE KNOW THAT THE LACK OF
NON-ADDICTIVE TREATMENTS FOR
PAIN CONTRIBUTED TO THE OPIOID
EPIDEMIC, WITH HUGE HEALTH
DISPARITIES IN PAIN.
NON-WHITE INDIVIDUALS AND WOMEN
ARE LESS LIKELY TO BE TREATED
DESPITE EXPERIENCING MORE PAIN
IN THE LAB AND CLINIC.
THESE ARE BOTH TOPICS THAT I
THINK WE AS PSYCHOLOGISTS CAN
MAKE CRITICAL INSIGHTS ON IN
TERMS OF REALLY KIND OF
UNDERSTANDING THE RELATIONSHIP
BETWEEN PAIN, SOCIAL PROCESSING
DECISIONS AND MORE AS DAVID
ALLUDED TO.
WE USE PLACEBO ANALGESIA, WHICH
REFERS TO REDUCTIONS IN PAIN DUE
TO INERT TREATMENTS, AS A
GUIDING MODEL TO HELP US ISOLATE
HOW EXPECTATIONS AND
PSYCHOSOCIAL CONTEXT SURROUNDING
TREATMENT DIRECTLY INFLUENCE
CLINICAL OUTCOMES.
WE THINK PLACEBO EFFECTS DEPEND
ON THE COMBINED PSYCHOLOGICAL
PROCESSES OF EXPECTATION FOR
PAIN RELIEF OR BENEFICIAL
OUTCOMES, SHIFTS IN EMOTION SO
FEELING LESS ANXIETY OR BETTER
BEING CARED FOR, AND THE ACTUAL
INTERPERSONAL SOCIAL TREATMENT
CONTEXT.
AND SO WE SYSTEMATICALLY
MANIPULATE AND MEASURE EFFECTS
ON PAIN.
NOW, MANY PEOPLE ARE AWARE OF
PLACEBO EFFECTS BECAUSE WE
GENERALLY TRY TO CONTROL FOR
THEM IN CLINICAL TRIALS IN ORDER
TO ISOLATE THE PURE EFFECT OF
THE DRUGS.
BUT BY INCLUDING -- I'LL TRY
THIS POINTER.
BY INCLUDING A NATURAL HISTORY
CONTROL GROUP, CLINICAL TRIALS
CAN ACTUALLY ISOLATE PLACEBO
EFFECT, NOT JUST THE DRUG
EFFECT.
IN 2001 AND AGAIN IN 2004 THESE
AUTHORS CONDUCTED A
META-ANALYSIS OF CLINICAL TRIALS
THAT COMPARED PLACEBO TREATMENT
WITH NO TREATMENT.
AND WHAT THEY FOUND IS THAT
PLACEBO EFFECTS WERE STRONGEST
IN PAIN AND SUBJECTIVE OUTCOMES.
ON ONE HAND, THIS COULD BE A
GREAT OPPORTUNITY FOR US TO
ISOLATE THESE PSYCHOLOGICAL
FACTORS, COMBINE WITH TREATMENT,
HELP PEOPLE HAVE THE BEST
OUTCOMES WHEN IT COMES TO PAIN,
DEPRESSION, DIFFERENT THINGS
THAT DEPEND ON SUBJECTIVE
DECISIONS.
ON THE OTHER HAND, IF THIS IS
JUST PEOPLE SAYING THEY ARE
FEELING BETTER WITHOUT ANY REAL
BIOLOGICAL CHANGES, THEN THESE
KINDS OF EFFECTS COULD JUST BE
PEOPLE WHINING ABOUT HOW THEY
ARE FEELING.
THIS HAS CATAPULTED RESEARCH IN
THE AREA OF MECHANISTIC WORK ON
PLACEBO AND PAIN RELIEF.
AND WITH THE KEY QUESTIONS BEING
CAN WE IDENTIFY PAIN-SPECIFIC
CIRCUITS, DO EXPECTATIONS
MODULATE PAIN THROUGH
PAIN-SPECIFIC CIRCUITS OR MORE
GENERAL CIRCUITS INVOLVED IN
EMOTION AND DECISION MAKING, AND
KIND OF MORE BROADLY HOW DO
PSYCHOSOCIAL FACTORS SHAPE PAIN.
SO, TO DO THIS, WE ADMINISTERED
PAIN IN THE LAB USING
SPECIALIZED DEVICES TO HEALTHY
VOLUNTEERS.
WE MEASURE HOW MUCH MAIN THIS
ELICITS.
USEEL TOOLS FROM NEUROSCIENCE
MANIPULATE THE SOCIAL CONTEXT,
AND USE BRAIN IMAGING TO STUDY
THE PATHWAYS.
TODAY I WILL GIVE EXAMPLES,
FIRST ISOLATING PAIN RESPONSES
AND HIGHLIGHTING SEX DIFFERENCES
IN THESE RELATIONSHIPS AS WELL
AS INTRODUCING THIS IDEA OF
USING BRAIN IMAGING TO IDENTIFY
PAIN BIOMARKERS.
NEXT I'LL TALK ABOUT OUR WORK ON
HOW EXPECTATIONS SHAPE PAIN AND
AFFECTIVE EXPERIENCE TO ADDRESS
THIS QUESTION WHETHER THIS IS
THROUGH PAIN SPECIFIC OR GENERAL
AFFECTIVE PROCESSES.
AND FINALLY I'LL INTRODUCE THE
MOST RECENT LINE OF WORK WE'VE
BEEN WORKING ON IN THE LAB,
REALLY LOOKING AT HOW SOCIAL
INFLUENCES SPECIFICALLY
INFLUENCE PAIN EXPECTATIONS AND
PAIN ASSESSMENT.
SO, PAIN IS DEFINED AS
UNPLEASANT SENSORY AND EMOTIONAL
EXPERIENCE ASSOCIATED WITH
ACTUAL OR POTENTIAL TISSUE
DAMAGE OR DESCRIBED IN TERMS OF
SUCH DAMAGE.
AS DAVID HIGHLIGHTED IN THE
INTRODUCTION THIS IS DISTINCT
FROM NOCICEPTION, THE NEURAL
PROCESS OF ENCODING THE NOXIOUS
STIMULUS ITSELF.
WE CAN DIVIDE PAIN INTO
INTENSITY, HEAT, WHERE IT IS ON
YOUR BODY VERSUS AFFECTIVE OR
MOTIVATIONAL COMPONENTS, THE
THINGS THAT DRIVE YOU TO WANT TO
ESCAPE THE PAIN AND CAN BE
MEASURED IN TERMS OF
UNPLEASANTNESS.
SO WHAT IT LOOKS LIKE IN THE LAB
IS WE HAVE PEOPLE COME IN, WE
USE THIS DEVICE CALLED A
THERMODE, HEAT IT AND YOU ASK
PEOPLE TO RATE IT USING 0-10
SCALE DEFINING TWO AS START OF
PAIN, EIGHT AS MAXIMUM PAIN
PEOPLE WOULD BE WILLING TO
TOLERATE.
IF IT WERE A HOT CUP OF COFFEE
AT 8 YOU COULD HOLD ON BUT
BEYOND THAT YOU PUT IT DOWN.
WE AP AVOIDED PLACES NOCICEPTORS
DON'T RESPOND, OVER CALIBRATION
CAN IDENTIFY UNIQUE THRESHOLDS,
TOLERANCE, AND CORRELATION
BETWEEN TEMPERATURE AND PAIN.
SO, IF PEOPLE HAVE RELIABLE
RELATIONSHIPS BETWEEN
TEMPERATURE AND PAIN, WE THEN
CAN BRING THEM BACK TO OUR OTHER
STUDIES WHERE WE ACTUALLY
MANIPULATE PSYCHOLOGICAL FACTORS
BECAUSE THERE'S A RELATIONSHIP
BETWEEN THE INPUT AND THEIR
EXPERIENCE.
PRIOR TO THE PANDEMIC WE DID
THIS IN 300 HEALTHY INDIVIDUALS,
170 CAME BACK FOR MULTIPLE
VISITS.
THREE POSTDOCS IN MY LAB
REALIZED THIS WAS A GREAT
OPPORTUNITY TO LOOK AT THE
RELIABILITY OF THESE MEASURES.
SO, WHAT THEY DID IS THEY LOOKED
AT PEOPLE WHO HAD COME BACK FOR
MULTIPLE VISITS.
YOU CAN SEE VISIT 1 ON X-AXIS,
VISIT 2 ON Y-AXIS, THAT'S THE
TEMPERATURE ASSOCIATED WITH
START OF PAIN.
WHAT YOU SEE IS STRONG
RELATIONSHIPS ACROSS INDIVIDUALS
AND THEN VERY CONSISTENT
RELATIONSHIPS BETWEEN PAIN
THRESHOLD ACROSS VISITS.
SIMILAR EFFECT WITH PAIN
TOLERANCE.
USING A MEASURE CALLED
INTRACLASS CORRELATION WHICH
LOOKS AT BETWEEN SUBJECT VERSUS
WITHIN-PERSON VARIABILITY WE SEE
MODERATE TO GOOD TOLERANCE.
WHAT THIS MEANS IS THAT THERE'S
SOMEWHAT STABLE INDIVIDUAL
DIFFERENCES, WE CAN RELIABLY
MANIPULATE THE STIMULUS, NOXIOUS
INPUT, MEASURE SUBJECTIVE PAIN.
WHEN WE LOOK AT THIS, IT'S LESS
CONSISTENT, THAT'S IN PART
BECAUSE WE HAVE SO MANY PEOPLE
WHO ARE UP HERE IN THE EXTREMELY
ACCURATE READINGS AS WELL AS
FACT IF LESS THAN .4 WE DON'T
BRING THEM BACK TO A SECOND
VISIT.
PEOPLE ARE GOOD AT RATING PAIN
IN RESPONSE TO CHANGES IN
TEMPERATURE.
SO, THIS KIND OF GIVES US --
HOPEFULLY GIVES YOU A FLAVOR OF
WHAT IT LOOKS LIKE FOR US TO
MANIPULATE PAIN IN THE LAB.
BUT WHAT WE REALIZED IS ACTUALLY
WITH THIS SAMPLE SIZE OF PEOPLE
WHO CAME BACK ACROSS MULTIPLE
VISITS WE HAD A REALLY NICE
BREAKDOWN IN TERMS OF SEX
DIFFERENCES BETWEEN OUR FEMALE
AND MALE PARTICIPANTS.
ALLOWING US TO ACTUALLY ASK
FORMALLY WHETHER WE SEE SEX
DIFFERENCES IN RELIABILITY.
THIS IS REALLY IMPORTANT BECAUSE
WOMEN HAVE TRADITIONALLY BEEN
EXCLUDED FROM RESEARCH IN PAIN
AND OTHER FIELDS BECAUSE OF
ASSUMPTION HORMONAL VARIABILITY
ACROSS THE CYCLE WILL MAKE THEM
LESS CONSISTENT IN THEIR PAIN.
WHAT DO WE SEE WHEN WE LOOK AT
CORRELATION MEASURES?
WE SEE WOMEN ARE MORE CONSISTENT
THAN MEN ACROSS VISITS FOR ALL
DIFFERENT PAIN MEASURES.
TO US, THIS CONTRADICTS
ASSUMPTION FEMALE PARTICIPANTS
WILL BE LESS CONSISTENT BECAUSE
OF HORMONAL FACTORS, AND
TRADITIONAL RATIONALE FROM
EXCLUDING WOMEN FROM RESEARCH,
WHETHER FEMALE PARTICIPANTS IN
HUMAN STUDIES OR IN ANIMAL WORK.
AND BECCA HAS SEASON INCREASED
VARIABILITY IN MALE RODENTS
TASKS OF FORAGING BEHAVIOR.
BUILDING ON THIS, A POSTDOC WHO
CAME TO MY LAB IN 2021, JULIE
PARSONS, WANTED TO LOOK AT THE
SAME GOODNESS OF FIT MEASURE, R
SQUARED, CORRELATION BETWEEN
TEMPERATURE AND PAIN, WHEN
PEOPLE DID TWO TYPES OF PAIN
ASSESSMENTS WITHIN A VISIT.
SO, PEOPLE EITHER EXPERIENCED
EIGHT SECOND STIMULI USING THE
THERMO OR THREE-SECOND STIMULI,
A DEVICE THAT IS BETTER FOR
DOING THINGS LIKE EEG STUDIES.
BEFORE WE WANTED TO USE THIS WE
WANTED TO SEE HOW SIMILAR THIS
IS.
SO, FOR FEMALE PARTICIPANTS R
SQUAREDS WERE THE SAME
REGARDLESS OF STIMULUS DURATION
OR TEMPERATURE THAT -- STIMULUS
DURATION OR THERMODE SIZE,
BECAUSE THEY ARE TWO DIFFERENT
SIZES.
WE SAW THE MALE PARTICIPANTS
WERE LESS ACCURATE WHEN TESTED
WITH THIS SECOND STIMULI THAN
EIGHT-SECOND STIMULI, AGAIN
SHOWING THAT OUR FEMALE
PARTICIPANTS WERE MORE
CONSISTENT ACROSS -- FIRST
ACROSS VISITS, AND NOW WITHIN
VISITS ACROSS STIMULUS
DURATIONS.
NOW, ALTHOUGH I THINK THIS KIND
OF SHOWS THAT THE HORMONAL
FLUCTUATIONS AREN'T LEADING TO
INCREASED VARIABILITY IN THE
WOMEN, WE DO CONSISTENTLY STILL
GET THE QUESTION, IS THERE
ANYTHING HAVING TO DO WITH THE
MENSTRUAL CYCLE.
JULIE DID A PILOT STUDY WHERE
SHE WENT BACK TO OUR FIRST STUDY
AND FOUND WHICH WOMEN HAD
REPORTED THEIR HORMONAL STATUS,
WHETHER OR NOT THEY WERE IN
CONTRACEPTIVES AS WELL AS WHICH
MENSTRUAL PHASE WHEN THEY CAME
IN, WHEN THE START OF THE CYCLE.
WE DIDN'T HAVE THIS DATA ON
EVERYBODY SO THESE ARE SMALL
SAMPLES BUT STILL OUR BEST WAY
TO ANSWER THE REQUEST WHETHER
THERE'S ANYTHING RELATED TO THE
MENSTRUAL CYCLE WITH THE MEASURE
OF PAIN.
THESE ARE WOMEN ON HORMONAL
CONTRACEPTIVES, AND ON THE
Y-AXIS I'M SHOWING THE
DIFFERENCE BETWEEN VISITS.
WE SEE BASICALLY IT'S ABSOLUTE
VALUE OF THE CHANGE BETWEEN
VISITS, SO THE THRESHOLD AND
TOLERANCE DIFFER BY ABOUT 1
DEGREE.
WHAT HAPPENS WHEN WE LOOK AT
WOMEN WHO ACTUALLY CAME IN AT
DIFFERENT PHASES IN THEIR CYCLE?
WHAT WE SEE IS THAT THE WOMEN
WHOSE CYCLES WITH CONTRACEPTIVS
HELD STABLE.
THERE WAS NO DIFFERENCE BETWEEN
THEM, WE DIDN'T SEE ANY
DIFFERENCE IN PAIN TOLERANCE,
AND WE SAW SIMILAR FINDINGS WHEN
WE LOOKED AT THAT R SQUARED
MEASURE, WITH SMALLER
DIFFERENCES BETWEEN SESSIONS IN
THE WOMEN WHO ARE NOT ACTUALLY
CYCLING.
BUT, AGAIN, IF WE COMPARE THIS
TO THE MEN, WE SEE IN ALL CASES
MEN ARE JUST AS VARIABLE, IF NOT
MORE.
SO, WHAT I HAVE SHOWN IN THIS
FIRST SECTION IS THAT WE CAN
RELIABLY ELICIT PAIN IN RESPONSE
TO NOXIOUS STIMULATION, USING
THIS THERMODE.
PAIN SENSITIVITY IS MORE
RELIABLE IN WOMEN THAN MEN
REGARDLESS OF HORMONAL STATUS.
AND PROVOCATIVE, WHEN WE'RE
TALKING ABOUT SEX AS A
BIOLOGICAL VARIABLE, INSTEAD OF
SAYING IS THE HORMONAL CYCLE
AFFECTING THINGS WE SHOULD
UNDERSTAND WHY MEN ARE SO MUCH
MORE VARIABLE ACROSS.
NOW THAT WE KNOW WE CAN ELICIT
PAIN IN THE LAB USING ACUTE
PAINFUL STIMULI WE CAN ASK
WHETHER OR NOT WE CAN IDENTIFY
BIOMARKERS FOR PAIN.
NOW, SEARCH FOR BIOMARKERS WAS
REALLY KIND OF ONE OF THE KEY
GOALS LAID OUT WITH NIH HEAL
INITIATIVE, AND THE REASON FOR
THAT IS BECAUSE THIS WOULD
REALLY PROVIDE AN OBJECTIVE
MEASURE TO AUGMENT SUBJECTIVE
PAIN READING.
NOW, IT'S IMPORTANT THAT THIS
NOT BE TO REPLACE PAIN RATINGS.
WE WANT THE PATIENT'S PAIN TO BE
FIRST AND FOREMOST.
BUT IN CASES WHERE THERE ARE
NON-VERBAL INDIVIDUALS OR THEN
THIS COULD ALSO SUPPLEMENT
SUBJECTIVE PAIN READINGS.
IN ADDITION IT ALLOWS US TO ASK
HOW PAIN IS MEDIATED IN
DIFFERENT CONTEXT, LIKE THE
QUESTION IS HOW IS PLACEBO
ANALGESIA MEDIATED.
OVER TIME YOU SEE KIND OF WHERE
WE'VE BEEN SINCE 2010 THERE.
SO, BECAUSE WE CAN OBJECTIVELY
MANIPULATE PAIN, AND WE HAVE MR
COMPATIBLE THERMODE WE CAN LOOK
AT THE NOCICEPTIVE PROCESS AT
PATHWAYS WHICH CAN BE IMAGED
USING FMRI, THIS COLLECTION OF
READINGS, WE GENERALLY SEE
STRONG ROBUST ACTIVATION IN
fMRI SCANNER WHEN PEOPLE
EXPERIENCE HIGH VERSUS LOW
INTENSITY HEAT.
AND WHILE THIS IS PROMISING, AND
FOR A LONG TIME KATHERINE
BUSHNELL SHOWED WE COULD FIND
RESPONSES TO PAIN, AND WE
ACTUALLY HAVE SHOWN WITHIN THESE
REGIONS DORSAL ANTERIOR
CINGULATE AND INSULA WE SEE
GRADIENTS MORE SPECIFIC TO PAIN
VERSUS NOCICEPTION AND CAN MAKE
DISTINCTIONS ABOUT THE
SUBJECTIVE EXPERIENCE.
THESE REGIONS ARE THE SAME BRAIN
REGIONS INVOLVED IN ANYTHING
SALIENT IN THE SCANNER SO THESE
ARE META-ANALYSES FROM A PROGRAM
CALLED NEUROSENSE.
YOU SEE BASICALLY ANY TASK THAT
INVOLVES ATTENTION AND
CONCENTRATION IS GOING TO ELICIT
ACTIVATION IN WHAT WE CALL
SALIENCE NETWORK, SPECIFIC TO
DORSAL ANTERIOR CINGULATE AND
INSULA.
LIKEWISE ANY STUDY THAT INVOLVES
A SENSE OF YOUR OWN BODY IS
GOING TO INVOLVE THE SAME
NETWORKS.
SO WE CAN'T REALLY SEE
ACTIVATION IN THIS SYSTEM AND
SAY THEREFORE THE PERSON IS
EXPERIENCING PAIN.
SO WHAT WE DID IS USED MACHINE
LEARNING, IN 2013 OR EARLIER,
AND DEVELOPED A BRAIN-BASED
CLASSIFIER, NEUROLOGIC PAIN
SIGNATURE, A PATTERN OF WEIGHTS
WHEN COMBINED WITH BRAIN
ACTIVATION PATTERN, SO ANY
CONTRAST FOR THOSE WHO DO fMRI
CAN PREDICT WHETHER SOMETHING IS
PAINFUL OR NOT, IN NEW
SCANNER,S, NEW STUDIES, NEW
SUBJECTS, IT'S BEEN ASTOUNDING
TO SEE HOW ACCURATE THIS HAS
BEEN OVER THE YEARS.
IMPORTANTLY THIS PATTERN OF
ACTIVATION IS HIGHLY SPECIFIC TO
PAIN SO IT CAN DIFFERENTIATE
BETWEEN PAIN AND OTHER TYPES OF
AVERSIVE EXPERIENCES.
JUST TO SHOW A RECENT EXAMPLE OF
THIS, THIS IS A STUDY LED BY A
FORMER -- CURRENT POST DOC AND
FORMER POSTDOC, NOW FACULTY AT
UNIVERSITY, WITH SUPPORT FROM
INDIVIDUALS AND LABORATORY BRAIN
AND COGNITION NIMH WERE ABLE TO
COMPARE PAIN WITH HEDONIC
PLEASANT OR UNPLEASANT CASE IN
THE fMRI SCANNER, WORKED WITH
A PHARMACY.
A LOT OF PEOPLE HELPED OVER THE
YEARS.
PEOPLE DID THAT EXACT SAME PAIN
CALIBRATION PROCEDURE OUTLINED
EARLIER BUT NOW THEY EXPERIENCED
NOT JUST HEAT BUT ALSO DIFFERENT
CONCENTRATIONS OF SALT OR SUGAR
OR NEUTRAL RINSE THAT MIMICS
ARTIFICIAL SALIVA.
YOU SEE SIMILAR ASSOCIATIONS
BETWEEN CHANGES IN TEMPERATURE
OR CONCENTRATION, ABLE TO PUT
EVERYBODY ON THE SAME RANGE,
PERCEIVED INTENSITY.
INTERESTINGLY, PEOPLE WHO HAD
HIGHER HEAT TOLERANCE ARE HIGHER
TOLERANCE FOR SUGAR AND SALT,
CROSS-MODAL EFFECT HERE.
WE HAD THESE PEOPLE EXPERIENCE
HEALTH, SALT, SUGAR IN fMRI
SCANNER, EITHER IN RESPONSE TO
STIMULI OR WITH CUES THAT
PREDICTED LEVELS, I'LL COME BACK
TO CUES LATER.
WHEN WE COMBINE ACROSS THE TWO
AVERSIVE OUTCOMES, AND LOOK AT
BRAIN REGIONS THAT COMPARE HIGH
VERSUS -- RESPOND TO HIGH VERSUS
LOW INTENSITY HEAT OR SALT, WHAT
WE SEE IS ACTIVATION OF THE
SALIENCE NETWORK.
WHEN WE LOOK AT THE NPS WE SEE
SIGNIFICANT NPS EXPRESSION WHEN
WE LOOK AT HEAT, HIGH VERSUS LOW
HEAT STIMULI, AND THAT IS
GREATER THAN SALT OR SUGAR.
INTERESTINGLY PEOPLE ACTUALLY
PERCEIVE THE SALT AS MORE
INTENSE IN THE SCANNER, SO IT'S
REALLY SHOWING THAT EVEN THOUGH
THE PERCEPTION MIGHT BE MORE
INTENSE, THIS SIGNATURE IS
REALLY SPECIFIC TO HEAT.
THERE'S OTHER SIGNATURES THAT
HAVE SINCE BEEN DEVELOPED, SUCH
AS THIS ONE FOR NEGATIVE AFFECT
IN GENERAL, TRAINED TO LOOK AT
DOMAIN GENERAL NEGATIVE AFFECT,
UNPLEASANT HEAT, VIDEOS, SOUNDS,
THINGS LIKE THAT, ILLUSTRATING
HOW NEURAL SIGNATURES CAN HELP
US HOW THEY ARE IN THE BRAIN.
RESPONSES TO PAINFUL STIMULATION
COMBINE PAIN SPECIFIC NETWORKS
WITH THOSE INVOLVED MORE
GENERALLY IN NEGATIVE AFFECT,
BOTH HAPPENING IN PARALLEL, AND
USING THESE CLASSIFIERS WE CAN
DISTINGUISH THEIR SEPARATE
CONTRIBUTIONS.
SO NOW WITH THAT FOUNDATION, WE
CAN ACTUALLY ASK HOW IS IT THEN
THAT EXPECTATIONS AND THINGS
LIKE PLACEBO SHAPE PAIN
EXPERIENCE.
SO -- I JUST WANT TO GET WATER.
SORRY.
WE CAN ASK WHETHER PLACEBOS
REDUCE PAIN THROUGH CHANGES IN
THESE PAIN-SPECIFIC MECHANISMS
OR THROUGH SHAPING MORE
DOMAIN-GENERAL MECHANISMS
INVOLVED IN SHIFT IN AFFECT,
THESE ARE THEORIZED IN THE AREA
OF PLACEBO ANALGESIA.
HOW DO WE DO THIS IN THE
SCANNER?
THIS IS A CLASSIC DESIGN, SO
BASICALLY PEOPLE ARE TOLD THAT
ONE -- THAT ABOUT -- INSTRUCTED
ABOUT TWO CREAMS, BOTH ARE
INERT, BUT ONE THEY ARE INFORMED
IS A POTENT ANALGESIC.
THEN DURING CONDITIONING PHASE,
THE CONTROL CREAM IS PAIRED WITH
HIGH INTENSITY PAIN STIMULUS BUT
UNBEKNOWNST TO PARTICIPANTS, THE
PLACEBO ANALGESIC CREAM PAIRED
WITH LOW INTENSITY STIMULUS TO
REINFORCE THE INSTRUCTIONS.
AND THEN DURING A TEST PHASE
PEOPLE GET THE SAME TEMPERATURE
ON BOTH SITES WHICH ALLOWS US TO
TEST WHETHER THIS COMBINED
INSTRUCTION PLUS LEARNING LEADS
TO EXPECTATIONS THAT IN TURN
DOWNREGULATE PAIN.
SO THIS DESIGN HAS BEEN USED BY
MANY RESEARCHERS AROUND THE
WORLD.
WE POOLED OUR DATA, SO WE HAD
OVER 600 INDIVIDUALS WHO HAD
GONE THROUGH THIS TYPE OF
PARADIGM, AND WHAT WE SEE IS
RELIABLE, SO WE CONDUCTED
META-ANALYSIS ACROSS THOSE
INDIVIDUALS AND SEE REDUCTION IN
PAIN WITH PLACEBO CREAM RELATIVE
TO THE CONTROL CREAM.
WHAT HAPPENS TO THE NPS?
WE SEE NO PLACEBO EFFECT ON THE
NPS.
SO THIS SUGGESTS THAT PLACEBOS
ARE REDUCING PAIN BUT NOT VIA
CHANGES IN THIS NEUROLOGIC PAIN
SIGNATURE PATTERN.
AND THIS IS IMPORTANT TO SAY
BECAUSE OTHER PSYCHOLOGICAL
PROCESSES DO SEEM TO IMPACT NPS,
SO THIS IS FROM A STUDY ON
MINDFULNESS, NPS ON THE Y-AXIS.
RELATIVE TO INSTRUCTION FOR
PEOPLE TO ACCEPT THE PAINFUL
HEAT RATHER THAN REACT, 25 OR
26% DROP IN NPS EXPRESSION.
WHEN WE DELIVER CUES THAT TELL
PEOPLE ABOUT INTENSITY OF THE
NOXIOUS STIMULATION BUT GIVE
THEM THE SAME TEMPERATURE DURING
TEST WE AGAIN SEE ABOUT A 20%
REDUCTION IN NPS, AND THEN WHEN
WE GIVE PEOPLE THE NEW OPIOID
AGONIST THROUGH AN I.V. WHETHER
WE TELL THEM WE'RE GIVING IT TO
THEM OR IN THE ABSENCE OF THEIR
KNOWLEDGE, WE SEE SIMILAR
EFFECTS ON THE NPS SUGGESTING
AGAIN THAT THIS INFORMATION
ACTIVATES OTHER CIRCUITS.
SO WHAT IS -- HOW IS PLACEBO
AFFECTING RESPONSES?
WE DID A META-ANALYSIS OF
PLACEBO OF BRAIN IMAGING STUDIES
OF PLACEBO, AND WHAT WE SEE IS
RELIABLE REDUCTION IN THE
REGIONS INVOLVED IN SALIENCE,
AND INCREASES WITH EXPECTATIONS
FOR REDUCTION IN THE FRONTAL
CORTEX, AND STRIATUM, AND THESE
REGIONS ARE INVOLVED IN SHIFT IN
AFFECT, EMOTION REGULATION,
VALUE-BASED LEARNING.
I'M GOING TO FOCUS IN PARTICULAR
ON THE ROLE OF THE ORBITO
FRONTAL CORTEX, THIS REGION IS A
HUB THAT RECEIVES INPUT FROM
LIMBIC AREAS, SENSORY AREAS, AND
ALSO PROJECTS TO DIFFERENT AREAS
THAT ARE CRITICAL FOR AFFECTIVE
PROCESSING, AND MAINTENANCE,
HOMEOSTASIS, LEARNING, ALL SORTS
OF FUNCTIONS.
AND WE HERE AT NIH ARE FORTUNATE
TO HAVE TWO OF THE WORLD LEADERS
IN THE FIELD, MURRAY AND
SHANBAUM, THIS IS A REVIEW OF
WHAT WE KNOW AFTER 20 YEARS THAT
WAS PUBLISHED IN 2007, SINCE
THEN PEOPLE HAVE CONTINUED TO
ARGUE ABOUT THE FUNCTION OF THE
OFC AND WE CAN GET INTO
SPECIFICS I THINK WE CAN SAY IN
GENERAL THIS REGION IS
FUNDAMENTAL FOR PREDICTION,
EXPECTED VALUE, LEARNING.
WE ARE TALKING ABOUT HOW THE OFC
IS NECESSARY LEARNING,
DEFINITELY INVOLVED FOR ASPECTS
OF PREDICTION AND LEARNING.
I ALSO WANT TO SAY -- OKAY, HERE
IS BACKWARDS.
THAT MOST OF THESE STUDIES HAVE
STUDIED THE ROLE OF THE OFC IN
CONTEXT OF REWARD.
DO WE SEE SIMILAR ROLES WHEN IT
COMES TO PAIN?
SO, THE WAY WE STUDY THIS IS TO
KIND OF -- SOMEWHAT ALLUDED TO
IN CONTEXT OF PLACEBO BUT WE
COMBINE CONDITIONING WITH VERBAL
INSTRUCTIONS IN MANY CASES TO
ELICIT EXPECTATIONS IN RESPONSE
TO PAIN PREDICTIVE CUES.
SO BASICALLY DURING CONDITIONING
PHASE, PEOPLE WILL HEAR ONE CUE
WHICH THEY ARE TOLD IS GOING TO
PREDICT LOW PAIN, ANOTHER CUE
HIGH PAIN, CONDITIONING TO
REINFORCE EXPECTATIONS.
DURING TEST PHASE PEOPLE EITHER
EXPERIENCE THE PREDICTED LEVEL
OR SINGLE LEVEL OF HEAT
CALIBRATED TO ELICIT MODERATE
PAIN.
NOW, WE HAVE -- THIS IS PAIN
READINGS IN RESPONSE TO MEDIUM
TRIAL ON THE Y-AXIS, AND ALL THE
DIFFERENT -- MANY DIFFERENT
STUDIES WHERE WE REPLICATED
EFFECTS.
WE SEE BOTH IN HEALTHY
VOLUNTEERS AS WELL AS YOUTH WITH
OR WITHOUT ANXIETY DISORDERS
RELIABLE REDUCTION OF 20% SO
BASICALLY WHEN THE SAME EXACT
TEMPERATURE IS PRECEDED BY LOW
PAIN CUES RELATIVE TO HIGH PAIN
CUES, AND THAT DIFFERENCE IS
ESSENTIALLY QUIFF EQUIVALENT TO
CLINICALLY SIGNIFICANT
DIFFERENCE, ALTHOUGH IN THE
CONTEXT OF ACUTE PAIN STIMULI I
AM CAREFUL NOT TO OVERREACH
THERE.
SO, WHAT HAPPENS IN THE CONTEXT
OF THIS TYPE OF LEARNED
EXPECTATION?
THE ORBITOFRONTAL CORTEX.
WHAT WE'VE SEEN OVER AND OVER IS
OFC IS CRITICAL FOR THIS TYPE OF
CUE-BASED EXPECTATION AND PAIN
MODULATION.
IN THE FIRST STUDY IN 2010, WE
SAW RESPONSES IN THE VENTRAL
STRIATUM AND VMPFC MEDIATED
WHICH DROVE TRIAL-BY-TRIAL PAIN.
WE'VE USED COMPUTATIONAL MODELS
TO TEASE APART ROLE OF THIS
REGION AND OTHERS IN THE CONTEXT
OF DYNAMIC LEARNING BY
INTRODUCING INSTRUCTIONS ABOUT
CHANGING CONTINGENCIES, AND WE
SEE THAT THE MPFC UPDATES WITH
INSTRUCTIONS, AMYGDALA AND OTHR
REGIONS RESPOND TO FEEDBACK.
MOST RECENT STUDY COME PINING
PAIN WITH SALT AND SUGAR, AGAIN
PRESENTED CUES THAT PREDICTED
HIGH OR LOW HEAT WITH TEST PHASE
MEDIUM TEMPERATURES, WE SEE THAT
WE SEE SIMILAR REDUCTIONS IN THE
INTENSITY RATING REGARDLESS OF
WHETHER PEOPLE EXPERIENCE HEAT,
SALT, SUGAR DURING fMRI
SCANNING ALTHOUGH SALT PERCEIVD
MORE INTENSE IN GENERAL,
MAGNITUDE IS SIMILAR, NO
DIFFERENCE BETWEEN GROUPS.
SO, WHEN WE LOOK AT WHAT HAPPENS
IN THE BRAIN DURING THIS PATH WE
SEE ALL THREE GROUPS SHOW LARGER
DEACTIVATION IN THE VMPC WITH
THE LOW CUE RELATIVE TO HIGH CUE
DURING ANTICIPATION OF THE
STIMULUS, AND THEN WHEN WE LOOK
AT RESPONSE TO THE ACTUAL
MODERATE INTENSITY STIMULUS
VMPFC IS LARGER FOR THE LEFT,
HERE WE SEE THERE'S MORE DID HE
ACTIVATION FOR THE HIGH CUE IN
THE HEAT GROUP AND MORE
DEACTIVATION FOR THE LOW CUE IN
THE SUGAR GROUP BECAUSE
BASICALLY THAT'S PREDICTING LESS
SUGAR OR MORE HEAT.
BUT ONE OF THE BIGGEST
LIMITATIONS OF fMRI THIS IS A
CORRELATION MEASURE.
WE SEE CORRELATIONS IN THE VMPFC
BUT TO WHAT EXTENT IS IT
CAUSEALLY LINKED TO EXPECTANCY
EFFECTS ON PAIN.
I WAS REALLY DELIGHTED TO HAVE
THE OPPORTUNITY TO TEST THIS IN
COLLABORATION WITH JULIAN, NOW A
FELLOW AT UCSF IN NEUROLOGY.
JULIAN IDENTIFIED FIVE PATIENTS
WITH OR BITOMENINGIOMAS, RARE
PATIENTS ENCOMPASSING MEDIAL
ORBITOFRONTAL CORTEX, COMPARED
TO HEALTHY CONTROL PARTICIPANTS,
GO THROUGH PAIN ASSESSMENT
PROCEDURE, CALIBRATION AT THE
BEGINNING AND EXPECTANCY TASK.
WE SAW THERE'S NO DIFFERENCE
BETWEEN HEALTHY CONTROLS AND
VMPFC PARTICIPANTS IN
RELATIONSHIP BETWEEN TEMPERATURE
AND PAIN, WHETHER WE MEASURED
INTENSITY OR UNPLEASANTNESS
DURING OUR CALIBRATION TASK.
HERE WE SEPARATED OUT INTENSITY
AND UNPLEASANTNESS BECAUSE OF
THE VMPFC ROLE IN VALUE.
WHAT HAPPENS WHEN WE LOOK AT
EXPECTANCY, HERE ON THE Y-AXIS
IS THE DIFFERENCE BETWEEN MEDIUM
HEAT IS PERCEIVED BY HIGH PAIN
CUE VERSUS LOW PAIN CUE, IN
HEALTHY CONTROLS WE AGAIN SEE
ABOUT A 2-POINT DIFFERENCE ON
THE INTENSITY SCALE, A LITTLE
BIT LESS FOR UNPLEASANTNESS.
WHEN WE LOOK AT PATIENTS WE SEE
THEY SHOW LARGER EFFECTS OF
EXPECTANCY ON SUBJECTIVE PAIN.
SO, THE LESION ACTUALLY ENHANCES
EXTENT TO WHICH PEOPLE REPORT
DIFFERENCES WHEN THE SAME
TEMPERATURE IS PRECEDED BY LOW
PAIN RELATIVE TO HIGH PAIN CUES.
I DON'T HAVE TIME TO GET INTO
THIS TODAY BUT WE THINK THIS IS
OVER RELIANCE ON VERBAL
INSTRUCTIONS AS OPPOSED TO NOT
HAVING EXPECTATIONS.
SO, WHAT I'VE SHOWN IN THE
SECOND PART OF MY TALK IS THAT
WE DO NOT SEE ANY RELIABLE
PLACEBO EFFECT ON NPS.
INSTEAD, EXPECTATIONS AFFECT
NEGATIVE AFFECT SYSTEMS, WE SEE
SIMILAR MECHANISMS BETWEEN PAIN,
AND OUR STUDY WITH LESION
PARTICIPANTS DID SHOW A CAUSAL
INFLUENCE ON THESE EXPECTANCY
EFFECTS.
SO, WE'RE GOOD ON TIME SO WITH
THE LAST THIRD OF MY TALK I'M
NOW GOING TO SWITCH TO TALKING
ABOUT SOCIAL INFLUENCES ON PAIN
EXPECTATIONS AND ASSESSMENT.
SO, THE VAST MAJORITY OF
RESEARCH IN THIS AREA IS PAIN
MODULATION HAS FOCUSED ON WHAT
WE CALL INTRAPERSONAL
PSYCHOLOGICAL FACTORS, THINGS
LIKE OUR EXPECTATION, EMOTION,
THE MEANING WE MIGHT ASCRIBE TO
AN EXPERIENCE, MEMORIES, AND OUR
PRIOR ASSOCIATIONS WITH THINGS
LIKE THE CLINICAL CONTEXT.
BUT WE KNOW THAT MOST CLINICAL
ENCOUNTERS DON'T HAPPEN IN
ISOLATION, EVEN WITH THE
PANDEMIC THERE'S STILL A
CLINICAL -- A SOCIAL CONTEXT
SURROUNDING TREATMENT.
AND SO WE HAVE MOVED SINCE 2018
SPEARHEADED FIRST BY LIZ MECCA,
NOW A PROGRAM OFFICER, IN NIA, A
SOCIAL NEUROSCIENTIST BEFORE MY
LAB, WE'VE MOVED FROM LOOKING AT
INTRAPERSONAL PROCESSES TO
INTERPERSONAL PROCESSES.
AND SO LIZ WANTED TO ASK WHETHER
OUR PERCEPTIONS OF PROVIDER'S
IMPACT ARE EXPECTATIONS ABOUT
PAIN.
WE KNOW FROM WORK IN THE CLINIC
AND IN LABORATORY MODELS THAT
THE PLACEBO RESPONSE CAN BE
INFLUENCED BY THE QUALITY OF THE
RELATIONSHIP BETWEEN A PATIENT
AND PROVIDER, BY THE WARMTH OR
COMPETENCE OF THE PROVIDER, SO
IN A SIMULATED CLINICAL
INTERACTION IF THE PROVIDER USES
YOUR NAME, VERSUS DOESN'T, OR
KNOCKS OVER A JAR OF WATER,
THOSE AFFECT THE MAGNITUDE OF
PLACEBO RESPONSE.
AND THEN ALSO LIZ HAS DONE
ELEGANT WORK LOOKING AT HOW
SIMILARITY OR CONCORDANCE WITH
PROVIDER CAN IMPACT PLACEBO IN A
PAIN MODEL.
BUT LIZ WANTED TO KNOW WHETHER
WE ALSO SEE EFFECTS OF SOCIAL
CONTEXT EVEN BASED ON INITIAL
IMPRESSION.
SO BASICALLY DO OUR FIRST
IMPRESSIONS OF PROVIDERS
INFLUENCE OUR EXPECTATIONS EVEN
BEFORE OUR INTERACTIONS.
SHE WANTED TO KNOW THIS BECAUSE
THERE'S LARGE LITERATURE IN
SOCIAL PSYCHOLOGY INDICATING
THAT PEOPLE PREFER MORE
COMPETENT-LOOKING FACES ACROSS
MANY DOMAINS, SO IF YOU ASK
PEOPLE TO JUDGE WHICH FACE LOOKS
MORE COMPETENT, THIS CAN PREDICT
OUTCOMES OF ELECTIONS WHEN
PEOPLE KNOW NOTHING ABOUT THE
CANDIDATES.
THERE'S A LARGE BODY OF WORK.
AND THESE FEATURES HAVE BEEN
IDENTIFIED THAT BASICALLY MAP
ONTO PERCEIVED COMPETENCE.
WE CAN LOOK AT COMPETENCE
IRRESPECTIVE OF WARMTH AND STUFF
LIKE THAT.
THIS IS DRIVEN BY ALEX TODOROF'S
LAB, THIS IS A FACE MORPHED TO
HAVE DIFFERENT LEVELS OF
COMPETENCE.
YOU CAN KIND OF MAKE YOUR OWN
JUDGMENT WHAT ARE THE FEATURES
THAT ARE ASSOCIATED WITH
COMPETENCE.
AND THIS IS, YOU KNOW, VALIDATED
ACROSS MANY LARGE SAMPLES OF
JUDGMENT.
SO LIZ FOCUSED ON ROLE OF
COMPETENCE AND SIMILARITY.
PERCEIVED SURGE IN COMPETENCE
CAN PREDICT RATINGS OF
TRUSTWORTHINESS OF PAIN IN THIRD
MOLAR EXTRACTION.
WE CONDUCT THE A SERIES OF FIVE
STUDIES ONLINE, PRESENTED
DIFFERENT HYPOTHETICAL PROVIDERS
TO PARTICIPANTS AND ASKED THEM
TO TELL US WHICH PARTICIPANTS
THEY WOULD PREFER FOR A
HYPOTHETICAL PAINFUL MEDICAL
PROCEDURE.
STUDIES ONE AND TWO PRESENTED
ORIGINAL MORPHED FACES THAT I
MENTIONED ON THE PREVIOUS SLIDE,
THREE AND FOUR USED THE SAME
COMPETENCE FEATURED ON MEN AND
WOMEN, AND IN STUDY FIVE REAL
PROVIDERS WHOSE FACES WEREN'T
MORPHED, REAL INDIVIDUALS, NOT
PROVIDERS, PICTURES OF REAL
INDIVIDUALS WHOSE FACES WERE NOT
MORPHED AND WHO VARIED BOTH IN
RACE, ETHNICITY, AND SEX.
DURING THE TASK, AGAIN PEOPLE
WOULD FIRST SELECT WHICH
PROVIDER THEY WOULD -- PEOPLE
FIRST REPORTED WHICH PROVIDER
THEY WOULD SELECT FOR PAINFUL
MEDICAL PROCEDURE, AND WERE
ASKED TO IMAGINE THE PROVIDER
WERE PERFORMING A PAINFUL
MEDICAL PROCEDURE ON YOU.
SORRY, WRONG BUTTON.
HOW PAINFUL WOULD THE PROCEDURE
BE.
AFTER THE PROCEDURE YOU MORE ARE
LIKELY TO USE OVER THE COUNTER
PRESCRIPTION MEDICATION AND HOW
SIMILAR DO YOU EXPECT THE
PROVIDER TO BE TO YOU.
I'M GOING TO BE PRESENTING
RESULTS OF META-ANALYSES
COLLAPSING DATA RATHER THAN
INDIVIDUALLY.
AND SO WHAT WE FOUND IS THAT THE
APPARENT COMPETENCE OF PROVIDER
INFLUENCED CHOICE AND
EXPECTATION.
X-AXIS IS THE LIKELIHOOD OF
CHOOSING THE MORE COMPETENT
PROVIDER.
AND SO YOU SEE THIS IS CHANCE.
YOU SEE PEOPLE ARE SELECTING THE
MORE COMPETENT PROVIDER
EXCEPTION FOR STUDY 3, WHERE
PEOPLE PREFERRED THE LESS
COMPETENT FEMALE FACE.
WE SAW ALSO ACROSS ALL THE
STUDIES THAT THE HIGHER THE
COMPETENCE, THE LESS PAIN PEOPLE
EXPECTED.
AND SO THIS SUGGESTS THAT SIMPLY
VIEWING THE FACES IS ASSOCIATED
WITH CONSISTENT JUDGMENTS ABOUT
EXPECTATIONS AND DECISIONS ABOUT
PAIN.
WE THINK THIS IS RELEVANT WHERE
WE SEE HEAD THOUGHTS -- HEAD
SHOTS OF PHYSICIANS EVEN IN THAT
REDUCED ENVIRONMENT WE'RE STILL
USING SOCIAL CUES TO MAKE
EXPECTATIONS AND DECISIONS.
WE ALSO SAW THAT SIMILARITY IN
SOCIAL CATEGORY IMPACTED
EXPECTATION, ACROSS STUDIES WE
SAW HIGHER THE SIMILARITY, LESS
PAIN PEOPLE EXPECTED.
AND WHEN WE ASKED ABOUT THE
EXPECTATIONS ABOUT ANALGESIC USE
WE FOUND THAT AFFECT OF
SIMILARITY WAS STRONGEST IN
WHITE PARTICIPANTS, LIKELY TO
REFLECT IN GROUP EFFECT BECAUSE
OF THE STUDIES INCLUDED ONLY
WHITE PROVIDERS FROM 1-4, AND NO
OTHER EFFECTS OF DEMOGRAPHIC ON
THESE DECISIONS.
IN STUDY 5 WHETHER WE ACTUALLY
HAD MANIPULATED OR PRESENTED
DIFFERENT PROVIDERS IN TERMS OF
RACE AND ETHNICITY OR SEX WE
FOUND SOCIAL STEREOTYPES SEEM O
HAVE IMPACTED PAIN AND
MEDICATION USE, HIGHEST
LIKELIHOOD OF OVER-THE-COUNTER
PRESCRIPTION FOR ASIAN
PROVIDERS, AND WE ALSO SAW
PEOPLE EXPECTED TO USE LESS
MEDICATION WHEN THE PROVIDER WAS
FEMALE RELATIVE TO WHEN IT WAS
MALE.
AND THESE I WANT TO SAY ARE ALL
DONE BETWEEN GROUPS SO PEOPLE
AREN'T MAKING JUDGMENTS BETWEEN
MALE OR FEMALE PROVIDERS SO
PEOPLE ONLY SAW PROVIDERS OF A
GIVEN RACE AND SEX COMBINATION.
SO THIS SUGGESTS TO US THAT --
WELL, THOSE DATA SUGGEST THAT
OUR STEREOTYPES INFLUENCE
DECISIONS ABOUT PROVIDERS.
WE KNOW STEREOTYPES FROM
PROVIDERS CAN IMPACT PAIN
ASSESSMENT.
THIS IS REALLY SHOWN IN THIS
GROUNDBREAKING WORK FROM HOFFMAN
IN 2016, NURSES AND FIRST-YEAR
MED STUDENTS ACTUALLY ENDORSE
FALSE BELIEFS ABOUT BIOLOGICAL
DIFFERENCES BETWEEN BLACK AND
WHITE PARTICIPANTS SPECIFICALLY
ALSO IN THE CONTEXT OF PAIN.
AND MORE RECENTLY, PETER,
UNIVERSITY OF DELAWARE, HAS DONE
PHENOMENAL WORK LOOKING AT KIND
OF HOW THESE TYPES OF RACIAL
BIASES AFFECT PAIN RECOGNITION.
HE HAD ACTORS DEPICT PAIN,
PRESENTED A VIDEO THAT RANGES
FROM NO PAIN AT ALL TO TOTALLY
PAINFUL EXPRESSION.
AND WHAT HE FOUND IS THAT HIS
PARTICIPANTS WHO WERE ALL WHITE
NEEDED MORE -- NEEDED TO SEE
LARGER EXPRESSIONS BEFORE
DETECTING PAIN ON THOSE BLACK
FACES, SO BASICALLY THE
THRESHOLD FOR IDENTIFYING
EMOTION OF PAINFUL WAS HIGHER
FOR BLACK FACES AND LARGER THIS
DIFFERENCE, THE LESS LIKELY THEY
WERE TO PRESCRIBE OPIOID
MEDICATION TO THE BLACK
PARTICIPANTS.
WE WANTED TO KNOW WHETHER
SIMILAR BIASES ARE PRESENT WHEN
PEOPLE EVALUATE REAL PAIN BASED
ON NON-VERBAL RESPONSES BECAUSE
THESE ARE ACTORS SO WE DON'T
REALLY KNOW HOW WELL THAT
GENERALIZES TO OUR RESPONSES TO
OTHER PEOPLE'S REAL NON-VERBAL
PAIN.
AND SO MY FORMER Ph.D. STUDENT
TROY WHO IS IN THE LAB SINCE THE
BEGINNING AND THEN DID HIS
Ph.D. WITH US AND IS NOW A
POSTDOC AT STANFORD, MEASURED
FACIAL RESPONSES AND ACUTE PAIN
IN OVER 100 HEALTHY INDIVIDUALS
WHO EXPERIENCED HEAT, SHOTS,
COLD PRESS OR PAIN IN THE LAB.
PEOPLE PROVIDED READINGS IN
TERMS OF HOW PAINFUL STIMULUS
WAS AND HOW INTENSE IT WAS AND
WE MEASURED USING HEAD-MOUNTED
GO PRO MEASURED PAIN ACROSS THE
TRIALS.
A SUBSET OF THESE INDIVIDUALS
AGREED TO HAVE THEIR VIDEOS
SHOWN TO OTHERS.
SO THAT WE CAN MEASURE HOW PAIN
ASSESSMENT SPECIFICALLY.
SO WE HAD 54 HEALTHY VOLUNTEERS
VIEW VIDEOS OF INDIVIDUALS, WE
CALL TARGETS, AND WE SELECTED
VIDEOS BALANCED FOR RACE,
GENDER, PAIN.
BASICALLY WE MADE SURE THAT
ACROSS RACE AND GENDER, WE
SELECTED VIDEOS THAT WERE
EQUIVALENT IN TERMS OF HOW MUCH
PAIN THEY DETECTED SO WE SHOWED
INNOCUOUS AND PAINFUL VIDEOS AND
HIGH AND LOW INTENSITY.
AND SO PEOPLE WOULD SEE THE
VIDEO AND RATE WHETHER OR NOT
THE PERSON WAS IN PAIN AND HOW
INTENSE IT WAS USING EXACT SAME
SCALES THE TARGETS USED
THEMSELVES.
SO HERE WHAT I'LL SHOW IS THE
BREAKDOWN AS A FUNCTION OF THE
APPARENT GENDER AND RACE OF THE
TARGET.
AND PEOPLE'S LIKELIHOOD OF
RATING THAT VIDEO AS PAINFUL.
AND WHAT WE SEE IS THAT EVEN
THOUGH THE VIDEOS DEPICTED EXACT
SAME AMOUNT OF PAIN ACROSS ALL
OF THE TARGETS, PEOPLE WERE LESS
LIKELY TO RATE THE VIDEO AS
PAINFUL WHEN IT DEPICTED BLACK
INDIVIDUALS RELATIVE TO WHITE
INDIVIDUALS.
IF WE BREAK THIS DOWN FURTHER
THE FUNCTION OF THE ACTUAL TYPE
OF VIDEO WE SELECTED, WHAT WE
FIND IS THIS IS SPECIFICALLY
DRIVEN BY A FAILURE TO IDENTIFY
PAIN IN BLACK MALES WHEN THEY
WERE EXPERIENCING PAIN.
AND WE ALSO EVALUATED A LOT OF
DIFFERENT SOCIAL FACTORS
INCLUDING IMPLICIT BIAS SCORES
AND THINGS LIKE THAT, AND THE
ONLY FACTOR THAT'S CORRELATED
WITH THESE DIFFERENCES WAS
ENDORSEMENT OF EXPLICIT RACISM
THROUGH THE MODERN RACISM SCALE,
PER
WE'RE ALL SUBJECT TO THE SAME
KINDS OF IMPLICIT SIGNALS IN OUR
SOCIETY IN THE U.S.
AND WE DID THIS STUDY ONLY IN
PEOPLE WHO WERE RAISED IN THE
U.S. AND ARE AMERICANS SO THAT
EVERYBODY IN THE STUDY WAS
EXPOSED TO THE SAME KIND OF
CULTURAL MESSAGING.
SO FINALLY THE LAST STUDY I WANT
TO PRESENT BRIEFLY, REALLY THIS
IS BRAND NEW DATA LED WITH HELP
FROM THE POSTDOCS HERE ALSO, WE
WANTED TO KNOW CAN WE IMPROVE
PAIN ASSESSMENT ACCURACY,
THERE'S BIASES, IS THERE
ANYTHING WE CAN DO TO HELP
PEOPLE BECOME MORE ACCURATE IN
JUDGING OTHER PEOPLE'S PAIN?
SO PEOPLE SAW THE SAME VIDEOS
THAT I JUST MENTIONED.
AND AGAIN MADE RATINGS ABOUT HOW
PAINFUL IT WAS, AS WELL AS
CONFIDENCE, AND NOW DIFFERENT
FROM THE PREVIOUS STUDY PEOPLE
GOT THE CHANCE TO SEE THAT SAME
PERSON OVER AND OVER.
SO THERE'S ONE CHANCE PEOPLE
JUST SIMPLY LEARN HOW TO JUDGE
SOMEBODY'S PAIN THROUGH
EXPERIENCE.
AND EVEN WITHOUT FEEDBACK.
AND A SECOND GROUP WE TOLD THEM
AFTER EACH TRIAL HOW MUCH PAIN
THE PERSON WAS ACTUALLY
EXPERIENCING.
AND SO WE COULD TEST WHETHER
THAT FEEDBACK IMPROVES PAIN
ASSESSMENT ACCURACY.
AND WHAT WE SEE ON THE Y-AXIS IS
ABSOLUTE DIFFERENCE OF THE --
ABSOLUTE VALUE OF DIFFERENCE
BETWEEN THE PERCEIVER'S PAIN
VERSUS TARGET'S ACTUAL PAIN, WE
SEE THAT DIFFERENCE DOES
DECREASE OVER TIME WITH AN
EXPERIENCE FOR EACH TARGET THAT
PEOPLE SAW.
SUGGESTING THAT SIMPLY THROUGH
PRACTICE, PEOPLE ARE GETTING
BETTER AT RATING PAIN, DIDN'T
DIFFER BETWEEN GROUPS.
WE SEE OVERALL THAT THE FEEDBACK
GROUP IS MORE ACCURATE THAN THE
NO-FEEDBACK GROUP IN TERMS OF
PAIN ASSESSMENT, WHETHER WE
LOOKED AT THIS DIFFERENCE IN
PAIN INTENSITY OR LIKELIHOOD OF
RATING PAIN AND BEING ACCURATE.
THIS INDICATES PAIN ASSESSMENT
ACCURACY IMPROVES THROUGH
EXPERIENCE, AND FEEDBACK
ENHANCES ACCURACY.
WE'RE NOW EXAMINING THE ROLE OF
GAZE POSITION SO WHERE PEOPLE
WERE LOOKING ON THE FACES.
THE ACTUAL NON-VERBAL FACIAL
EXPRESSIONS, HOW PEOPLE USE
FEEDBACK FROM THE FACE TO MAKE
THEIR JUDGMENT, AND THE LEARNING
PROCESS THROUGH COLLABORATION
WITH ANGELA LANGDON, WHO IS
HERE, AND BRUNO EVERBECK.
OUR FIRST IMPRESSIONS OF OUR
PROVIDERS DO SHAPE OUR
EXPECTATIONS ABOUT PAINFUL
PROCEDURES, THAT SOCIAL
STEREOTYPES IMPACT PAIN
EXPECTATIONS AND ASSESSMENT, AND
THAT WE CAN IMPROVE ACCURACY IN
PAIN ASSESSMENT AND IN THE
FUTURE WE HOPE TO TEST WHETHER
THIS IN TURN CAN REDUCE THOSE
BIASES THAT WE SEE.
SO, OVERALL, WHAT I'VE SHOWN
TODAY IS THAT PAIN PERCEPTION
INVOLVES PAIN-SPECIFIC PROCESSES
AND CIRCUITS GENERALLY INVOLVED
IN PAIN AFFECT AND DECISION
MAKING.
PLACEBO ANALGESIA SEEMS TO
REFLECT SHIFTS IN EMOTION,
LEARNING, EXPECTATIONS, RATHER
THAN CHANGES IN NOCICEPTION, BUT
THIS DOESN'T MEAN PLACEBO
EFFECTS AREN'T REAL.
IT REALLY CAN BE WE KNOW EMOTION
IS REAL, WELL-BEING IS REAL.
SHIFTING SOMEBODY'S ANXIETY OR
IMPROVING POSITIVE AFFECT CAN
HAVE REAL EFFECT ON HEALTH,
SOMETHING PROVIDERS SHOULD THINK
ABOUT IN TERMS OF HOW YOU TREAT
THE TREATMENT, TIMES, BECAUSE
THEY ARE AREN'T CHANGING
NOCICEPTION DOESN'T MEAN THIS IS
REPORT BIAS.
FINALLY HOW ASSOCIATE FACTORS
SHAPE PAIN, WHERE WE SEE THE
SOCIAL CONTEXT AND STEREOTYPES
IMPACT PAIN BUT WE ALSO SEE
IMPORTANT SEX DIFFERENCES EVEN
IN THE MOST BASIC RELATIONSHIPS
BETWEEN NOCICEPTION AND PAIN.
SO WHERE ARE WE GOING FROM HERE?
WE HAVE HAD THE OPPORTUNITY TO
COLLABORATE WITH PEOPLE WHO ARE
RECORDING DIRECTLY FROM THE
GRAY, HOW THE SUBCORTICAL
CIRCUITS CONTRIBUTE TO PAIN AND
EMOTION, AND WHETHER THIS IS
ALTERED IN PAIN GROUPS SUCH AS
INDIVIDUALS WITH CHRONIC PAIN OR
MAJOR DEPRESSION.
WE FOR A LONG TIME HAVE WANTED
TO TEST THE ROLE OF ENDOGENOUS
OPIOIDS AND DOPAMINE, WE'RE
HOPING TO DO PHARMACOLOGICAL
WORK, POTENTIALLY USE NEW
SIMULTANEOUS PET SCANNER TO LOOK
AT HOW OPIOIDS AND DOPAMINE
CONTRIBUTE TO MODULATORY
MECHANISMS INVOLVED IN PLACEBO.
AND FINALLY IN JUST A COUPLE
WEEKS WE'RE PLANNING TO BEGIN A
STUDY LOOKING AT NEURAL
MECHANISMS OF THIS SOCIAL
LEARNING, AND OVER TIME ACTUALLY
SEE WHETHER THIS REDUCES PAIN
ASSESSMENT BIASES.
SO WITH THAT, I WANT TO ONCE
AGAIN ACKNOWLEDGE ALL THE FORMER
STAFF AND TRAINEES WHO
CONTRIBUTED TO THIS WORK, AS
WELL AS THE CRITICAL CLINICAL
SUPPORT WE'VE GOTTEN FROM NURSE
PRACTITIONERS, AND THEN THE
PROGRAM SUPPORT AND WONDERFUL
COLLABORATIONS AND MENTORSHIP
I'VE HAD OVER THE YEARS WITHIN
NCCIH, GOING TO KATHERINE
BUSHNELL WHO HIRED ME, ALL THESE
WONDERFUL PEOPLE, WHO HAVE
HELPED OUR TEAM GO.
OUR COLLEAGUES, COLLABORATORS
AND MENTORS IN NIMH AND NIDA,
AND FINALLY MY FORMER MENTORS
AND COLLABORATORS OUTSIDE OF THE
NIH.
WE HAVE POSITIONS AVAILABLE AND
I'M HAPPY TO TAKE QUESTIONS.
[APPLAUSE]
>> OPEN FOR QUESTIONS, PLEASE
COME TO THE MIC.
I'LL BE FIELDING ANY QUESTIONS.
>> HAVE YOU LOOKED AT THE AFFECT
OF DISTRACTION ON PAIN
PERCEPTION?
>> GREAT QUESTION.
SO WE HAVE DONE SOME STUDIES TO
TRY TO LOOK AT THE AFFECT OF
ATTENTION WHICH PROBABLY WERE
MEDIATED BY DISTRACTION, WHETHER
EXPECTATIONS CAUSE YOU TO PAY
ATTENTION DIFFERENTLY TO THE
STIMULUS.
SO, WE HAVEN'T DONE -- WE FOUND
BASICALLY THAT WHEN WE HAVE
PEOPLE DO TWO -- HAVE TOO MUCH
COGNITIVE LOAD WE SEE REDUCTION
IN PAIN SO THAT'S PROBABLY
MEDIATED BY CHANGES IN
DISTRACTION BUT WE HAVEN'T
REALLY TRIED SPECIFICALLY TO
MANIPULATE DISTRACTION IN THE
LAB.
SO I THINK THAT'S SOMETHING WE
HAVE TO ALWAYS KIND OF KEEP AN
EYE OUT ON, KATHERINE BUSHNELL,
HER LAB HAD DONE A LOT OF WORK
ON ATTENTION DISTRACTION AND
FOCUS ON PAIN AND SHOWED THAT IT
CAN CHANGE BRAIN RESPONSES AND
PAIN IN THE WAY THAT WE THINK
WE'RE SEEING IN OUR LAB TOO.
THANKS.
RICHARD?
>> HI.
A QUESTION ABOUT EARLY SLIDE,
QUESTION ABOUT THE LAST SECTION.
>> OKAY.
>> IN THE EARLY SLIDE YOU SHOWED
CORRELATIONS TEST 1, TEST 2, ON
PAIN RATING.
>> YES.
>> MOST PEOPLE HAD HIGH
CORRELATIONS.
>> YES.
>> THERE WERE ABOUT TEN I THINK
WHO HAD LOW CORRELATION.
DID YOU LOOK AT WHO THEY WERE?
>> THERE'S SOMETHING REALLY
INTERESTING ABOUT THAT.
FIRST OF ALL, I THINK I'LL HAVE
A HARD TIME -- LET ME GO BACK.
>> IT WAS REALLY EARLY, YEAH.
>> HAPPY TO TALK ABOUT IT
BECAUSE WE THINK THESE ARE
REALLY INTERESTING AND PROBABLY
AT THIS POINT DO HAVE THE SAMPLE
SIZE TO BE ABLE TO LOOK AT THEM.
>> WAY EARLY.
>> IT'S HERE.
>> OKAY.
>> WAIT, NO THE ONE BEFORE.
BASICALLY WHAT I WANT TO DRAW
YOUR ATTENTION TO IS THAT THIS
IS LIMITED TO PEOPLE WHO WERE
INVITED BACK FOR THE SECOND
VISIT.
THESE ARE ACTUALLY PEOPLE WHO
ORIGINALLY HAD R SQUARED VALUES
.4 BUT SECOND TIME NO LONGER
ELIGIBLE BASED ON THAT CRITERIA.
WE SEE IN GENERAL IF I WOULD
HAVE JUST SHOWN YOU THE 360 OR
400 PEOPLE, 10% OF PEOPLE ARE R
SQUARED LESS THAN .4, 10% HAVE
TOLERANCE VALUES HIGHER THAN 50
WHICH MEAN WE CAN'T ACTUALLY
SAFELY ADMINISTER.
WE'VE NEVER LOOKED AT WHAT
FACTORS PREDICT SOMEBODY'S R
SQUARED VALUES WHICH I THINK IS
A REALLY IMPORTANT QUESTION.
AND IT'S PROBABLY AT THIS POINT
ABOUT 50 OR SO PEOPLE WHO HAVE
THAT.
WE HAVE THE DATA IF YOU'D LIKE
TO LOOK AT IT.
>> I MIGHT.
>> IT WOULD BE REALLY COOL, YES.
>> AND AT THE END WHEN YOU WERE
LOOKING AT PEOPLE'S RATINGS
BASED ON SEX AND RACE, DID YOU
HAVE ENOUGH PEOPLE, PARTICIPANTS
OF DIFFERENT SEXES AND RACES, TO
LOOK AT CROSS-CORRELATION?
>> YES, GREAT QUESTION.
WE'VE SEEN THIS IN ALL OF OUR
STUDIES.
WE -- IF WE LOOK AT -- I'LL CALL
IT TARGET PERCEIVER CONCORDANCE,
WHETHER YOU SHARE THE SAME
IDENTITY AS TARGET WITH RESPECT
TO RACE OR GENDER REALLY DOESN'T
AFFECT DECISIONS BUT HOW SIMILAR
YOU SAY YOU FEEL TO THE TARGET
DOES IN EVERY SINGLE STUDY WE'VE
DONE.
WE JUST SAW THIS AGAIN IN THE
MOST RECENT LEARNING TASK.
SO PROBABLY SOME PEOPLE MIGHT BE
USING THOSE KINDS OF FEATURES TO
SAY I FEEL MORE SIMILAR BUT
THERE'S SOMETHING THAT GOES
BEYOND JUST KIND OF CENSUS
CATEGORIES THAT IS DRIVING THAT
SIMILARITY.
AND WE'RE SETTING UP NOW TO DO
HOPEFULLY LIKE IN THE NEXT WEEK
OR SO WE'LL BE LAUNCHING THIS IN
A MUCH LARGER SAMPLE ONLINE TO
LOOK IN A MORE CONSISTENT WAY
BECAUSE THESE ARE SMALL SAMPLES.
>> INTERESTING.
THANKS.
>> THANK YOU.
>> HI.
THAT WAS A GREAT TALK.
TWO QUESTIONS.
ONE, I GUESS SIMILAR TO THE
QUESTION THAT ROLAND ASKED.
SO, HAVE YOU LOOKED TO SEE IF
PERCEPTION OF PAIN IS INFLUENCED
BY TIME OF DAY?
SO DO PEOPL PERCEIVE DIFFERENTLY
EARLY IN THE MORNING VERSE U.S.
LATE AT NIGHT AND A MORE GENERAL
QUESTION, THESE SIGNATURES THAT
YOU SEE DURING ACUTE PAIN USING
fMRI, HOW DO THOSE COMPARE TO
WHAT IS SEEN FOR PEOPLE WHO HAVE
CHRONIC PAIN?
>> THANK YOU FOR THOSE
QUESTIONS.
WELL, FIRST QUESTION, NO.
WE'VE NEVER LOOKED AT TIME OF
DAY.
WE'RE SORT OF CONSTRAINED BY,
YOU KNOW, OUR CLINICAL
AVAILABILITY.
>> SURE, SURE.
>> WE -- YOU KNOW, I KNOW SYLVIA
IS DOING WORK NOW WITH CORTISOL
AND STRESS.
WE COULD ACTUALLY LOOK AT
DIURNAL CHANGES IN CORTISOL BUT
EVEN I'LL GO MORE BROADLY, OUR
ANALYSIS OF MENSTRUAL CYCLE,
THAT WAS ALSO LIMITED BECAUSE WE
DIDN'T ACTUALLY MEASURE THE
HORMONES SPECIFICALLY.
I THINK IT WOULD BE REALLY GREAT
AT SOME POINT FOR US TO INCLUDE
THOSE MEASURES AND THEN WE WOULD
DEFINITELY WANT TO TAKE THAT
INTO ACCOUNT.
WITH RESPECT TO DIFFERENCE
BETWEEN NPS IN PATIENT GROUPS,
IT DOESN'T PREDICT IN GROUPS.
IT PREDICTSES NOCICEPTIVE PAIN,
NOT CHRONIC PAIN.
A COLLEAGUE HAS DEVELOPED A
BRAIN-BASED CLASSIFIER THAT CAN
PREDICT PAIN IN INDIVIDUALS WITH
FIBROMYALGIA, REALLY A GENERAL
SENSORY RESPONSE.
IT'S NOT VERY SPECIFIC TO PAIN.
SO WE KIND OF THINK ABOUT THIS
AS THE NOCICEPTIVE CIRCUIT, AND
CAN SEE THAT IT ALSO PREDICTS
CIRCUITS IN PARTICIPANTS WITH
CHRONIC PAIN BUT IDENTIFYING THE
BRAIN SYSTEMS THAT ARE
RESPONSIBLE FOR CHRONIC PAIN
SPECIFICALLY IS AN ENTIRELY
DIFFERENT KIND OF NETWORK WE
ASSUME AND THAT'S SOMETHING
PEOPLE IN THE HEAL INITIATIVE
AND THE COMMON FUND HAVE BEEN
WORKING ON HARD.
HOPEFULLY IN THE NEXT COUPLE
YEARS WE'LL HAVE BRAIN-BASED
CLASSIFIERS FOR CHRONIC PAIN AS
WELL.
>> WE HAVE A QUESTION FROM
ONLINE FROM DR. PAO, GREAT TALK.
HAVE YOU CONSIDERED ANY PATIENT
POPULATIONS SUCH AS SOMATIC
SYMPTOM DISORDER PATIENTS TO
TEST EXPECTANCIES IN LEARNING
PARADIGMS?
>> THANK YOU FOR THAT QUESTION.
I GUESS I WILL ANSWER IN A
COUPLE WAYS.
WE ARE ALWAYS ENTHUSIASTIC TO
PARTNER WITH GROUPS THAT HAVE
ACCESS TO CLINICAL PATIENTS WHO
MIGHT SPECIFICALLY SHOW
DIFFERENCES IN THESE KINDS OF
PROCESSES, SO WE HAVE THE PAIN
RESEARCH CENTERS, GREAT TIME TO
ADVERTISE IT.
WE'D LOVE TO KIND OF STAY IN
TOUCH WITH WHAT ASPECTS OUR TASK
MIGHT MAKE SENSE TO TEST ACROSS
A WIDE RANGE OF PATIENTS AND SO
IF THE SOMATOSENSORY OR SENSORY
SYMPTOM DISORDER, THAT WOULD BE
GREAT TO TALK MORE ABOUT THAT.
ALSO, WE HAVE SOME POTENTIAL
UPCOMING COLLABORATIONS, WITH
SYLVIA LOPEZ GUZMAN, LOOKING AT
PAN IN THE CONTEXT OF NEGATIVE
AFFECT AND DECISIONS THAT MIGHT
BE RELATED TO ADDICTION.
AND ALSO WITH CARLOS IN THE
CONTEXT OF SOME POTENTIAL
NON-OPIOID ANALGESICS THAT WE'RE
REALLY EXCITED ABOUT FOR THE
FUTURE BUT KIND OF BEYOND THE
SCOPE OF THIS TALK.
THAT'S DEFINITELY THE NEXT PHASE
OF OUR WORK WE HOPE TO MOVE FROM
MECHANISTIC INTO WHAT'S GOING ON
IN PATIENTS.
>> GREAT.
>> AWESOME.
REALLY NICE TALK.
>> THANK YOU.
>> 55 PAPERS IS A LOT.
TWO QUESTIONS.
THE FIRST HAS TWO PRONGS.
IT'S MORE ABOUT META BELIEFS IN
PEOPLE, LIKE HAVE YOU LOOKED AT
WHETHER THE PLACEBO EFFECT
DIFFERS IN PEOPLE THAT HAVE
BELIEFS WELL-BEING CAN CHANGE
THEIR LIFE, OR FAITH AND THINGS
LIKE THAT AND A FOLLOW-UP TO
THAT, THAT COMPONENT, LIKE DO
YOU THINK IT WOULD BE THE SAME
CIRCUITS THAT WOULD GET
ACTIVATED IN THOSE KIND OF
CONDITIONS AS PLACEBO FOR PAIN?
>> YES.
A THIRD QUESTION?
>> THE SECOND QUESTION.
>> CAN I ANSWER THOSE?
I WANT TO HEAR THE NEXT QUESTION
TOO.
SO, WE ORIGINALLY IN THIS SAME
TASK WE USED THIS TASK AT ONE
POINT TO EXPLORE WHETHER WE
MIGHT BE ABLE TO IDENTIFY
IMPLICIT MARKERS THAT WERE TO
HELP US SEE WHEN SOMEBODY
EXPERIENCES A PLACEBO, DO THEY
EXPERIENCE LESS PAIN BUT ALSO
BECOME MORE UNCERTAIN ABOUT
THEIR PAIN?
SO MAYBE WHAT HAPPENS IS YOU
KIND OF LIKE TELL ME YOU FEEL
BETTER BUT YOU'RE ALSO NOT QUITE
CERTAIN, AND SO WHAT WE DID IS
USED EYE TRACKING AND HOW PEOPLE
LOOKED AT THE SCALE TO SEE
WHETHER -- AND WE INCLUDED
SUBJECTIVE CONFIDENCE RATINGS
WHEN THEY WERE LESS CONFIDENT
LOOKED AROUND THE SCALE MORE AND
IF THAT WERE THE CASE WE WOULD
HAVE BEEN ABLE TO USE THAT AS AN
IMPLICIT MEASURE TO TEST WHETHER
PEOPLE REPORT LESS PAIN BUT
ACTUALLY ARE LESS CERTAIN ABOUT
THEIR PAIN.
APPROACHES LIKE MOUSE TRACKING
ALSO THAT WE'VE EXPLORED USING
FOR THAT.
WE DID SEE THAT PEOPLE WITH
HIGHER R SQUARED SHOWED STRONGER
RELATIONSHIP BETWEEN FIXATION ON
THE SCALE AND CONFIDENCE BUT
DIDN'T GENERALIZE ACROSS
EVERYBODY, WE HAVEN'T LOOKED AT
EVERYBODY BUT IT'S IMPORTANT TO
ME, STILL A HYPOTHESIS THAT I
KEEP IN THE BACK OF MY HEAD.
WITH RESPECT TO PEOPLE WHO MAYBE
HAVE MORE SPIRITUAL BELIEFS OR
KIND OF DESIRE FOR RELIEF, THE
FIELD OF RESEARCH, ONE THING I
MENTION IS THE MEANING RESPONSE,
WHEN WE TALK ABOUT WHAT IS
PLACEBO, THERE IS THIS IDEA THAT
IT MIGHT BE KIND OF MAKING MORE
MEANING OUT OF THE CLINICAL
CONTEXT.
AND PEOPLE -- SO IT'S LESS ABOUT
SOME STUDIES IN PATIENTS
SUGGESTING IT'S LESS ABOUT
EXPECTATION OF RELIEF BUT RATHER
DESIRE FOR RELIEF WHICH COULD
ACTUALLY THEN BRING ON BOARD
OTHER THINGS YOU'RE TALKING
ABOUT.
LASTLY, A COLLEAGUE KATIA AT
OXFORD DID A STUDY WHERE SHE
LOOKED AT RELIGIOUS INDIVIDUALS
INSTEAD OF PRESENTING EXPECTANCY
CUES DID PRESENT RELIGIOUS CUES,
AND SHE SHOWED SIMILAR
MODULATION OF PAIN IN ANTERIOR
INSULA SO PEOPLE HAVE USED THAT
KIND OF MEANING AS A TYPE OF
EXPECTATION.
WHETHER PEOPLE WHO ENDORSE THOSE
BELIEFS SHOW LARGER PLACEBO
RESPONSES IN CLINIC I'M NOT SURE
ABOUT.
SO THANKS FOR THAT FIRST
QUESTION.
SECOND?
>> IF THEY WERE TO SAY THIS
PERSON IS NOT VERY CONFIDENT,
NOT SO MUCH PLACEBO RESPONSE, IF
YOU CAME BACK AND TOLD THEM
THAT'S ACTUALLY OUR BEST PERSON
THAT TRAINED AT STANFORD, THEY
ARE THE PAIN WIZARD, DO YOU
THINK THEY WOULD UNMASK?
>> I LOVE THAT QUESTION.
I WAS TELLING SOMEONE, PEOPLE
WOULD CHOOSE A MALE PROVIDER BUT
HAVING A FEMALE PROVIDER MAKES
YOU MORE LIKELY TO SURVIVE
REGARDLESS OF YOUR GENDER SO
TEACHING PEOPLE WHAT IS
IMPORTANT FOR THE HEALTH COULD
HOPEFULLY OVERRIDE EXPECTATIONS.
SO WE HAVE ONLY LOOKED AT THAT
QUESTION IN THE CONTEXT OF MY
WORK ON AVERSIVE LEARNING WHERE
WE ACTUALLY KIND OF PIT
INSTRUCTION AGAINST FEEDBACK
HISTORY AND WE THINK IT DEPENDS
ON CIRCUMSTANCES.
IF WE USED SOCIAL INSTEAD OF
AVERSIVE STIMULI I IMAGINE WE
COULD SEE PARALLEL DUAL
PROCESSES FOR TRACKING KNOWLEDGE
AND HOPEFULLY GETTING THE
PREDICTIONERS TO UPDATE EXPECTED
BELIEFS.
I LIKE THAT IDEA.
>> WE HAVE TIME FOR ONE MORE
QUESTION.
DR. CARRASQUILLO?
>> BEAUTIFUL TALK, LAUREN.
>> THANKS.
>> TWO QUESTIONS.
YOU CHOOSE, I'LL TELL YOU TWO,
YOU CHOOSE WHICH TO ANSWER.
>> OR I'LL PUT THEM TOGETHER.
>> ONE OF THEM IS EASY, I'VE
HEARD YOU SAY MANY TIMES ONE OF
THE ADVANTAGES TO BE HERE IS
THAT YOU GET PEOPLE THAT ARE OF
DIFFERENT AGES THAN WHEN YOU ARE
AT COLLEGE INSTITUTIONS.
>> YES, YES.
>> PARTICIPANTS.
SO I WAS WONDERING IF ANYTHING
YOU'VE SHOWN IS -- IF YOU SEE
ANYTHING RELATED TO AGE,
PARTICULARLY BOTH OF COURSE THE
PARTICIPANTS, BUT ALSO IN THE
LATER PART, WONDERING IF PEOPLE
PERCEIVED OLDER PEOPLE AS WISER
AND MORE COMPETENT THAN YOUNGER
PEOPLE EVEN IF THEY HAVE THE
SAME COMPETENCY ON PAPER, AND
THEN HOW PREVIOUS LIFE TRAUMA,
WHETHER PHYSICAL OR MENTAL, LIKE
FITS INTO EVERYTHING THAT YOU'VE
SAID, EXPECTATIONS, YOU KNOW,
ALL OF THAT.
THE SECOND ONE OF COURSE LOVE
YOUR SEX/GENDER BECAUSE IT'S
VERY UNEXPECTED AND IMPORTANT,
WAS WONDERING WITH THE FEMALES
IF YOU HAVE BROKEN THEM UP IN
REPRODUCTIVE LIKE, YOU KNOW,
STATUS OR WHETHER THEY HAVE HAD
CHILDREN OR NOT HAVE CHILDREN,
AND THEN ALSO WHETHER YOU'VE
TAKEN HISTORY OF HOW PAINFUL
THEIR MENSTRUAL CYCLES ARE AND
THINGS LIKE THAT.
>> OKAY.
SO I'LL ANSWER --
>> WE CAN TALK ABOUT IT LATER
TOO.
>> THANK YOU FOR THE QUESTION.
WE'VE TALKED ABOUT US NEEDING TO
ADD THIS QUESTION ABOUT WHETHER
PEOPLE HAVE HAD PREGNANCY, WHAT
WAS THEIR EXPERIENCE.
I CAME BACK TO THE LAB
IMMEDIATELY, WE NEED TO DO THIS.
WE NEVER ASKED ANYTHING ABOUT
THAT.
SO I GENERALLY THINK THAT AS WE
RAMP UP NEW STUDIES WE WANT TO
INCLUDE THOSE QUESTIONS.
I THINK IT'S A GREAT PROJECT FOR
A POSTDOC TO KIND OF DO
SECONDARY RESEARCH AND GO BACK
AND ACTUALLY SEE ABOUT WHETHER
PEOPLE'S EXPERIENCE AFFECTS
THEIR RESPONSES IN THE LAB.
SO, WE HAVEN'T BUT I HOPE THAT'S
SOMETHING WE DO GOING FORWARD.
THE OTHER QUESTION I WILL JUST
TALK ABOUT THE LIFESPAN AND
TRAUMA HISTORY.
WE'RE NOW INTERESTED IN LOOKING
AT CHILDHOOD TRAUMA, COLLECTED
IN THE PAST BUT NOT
CONSISTENTLY, WE DON'T QUITE
HAVE THE NUMBERS.
THERE'S A MEASURE THAT WE, NIDA,
NIAAA AND NIMH WERE GOING TO USE
IN HEALTHY VOLUNTEER PROTOCOLS
TO LOOK SYSTEMATICALLY ABOUT HOW
CHILDHOOD TRAUMA AFFECTS PAIN,
ADDICTION, MENTAL HEALTH.
WE DECIDED THAT IN 2017 I THINK
AND HAVEN'T COME BACK TOGETHER.
AND SO WE HAVEN'T LOOKED AT THAT
ALONE IN THE LAB YET BUT HOPE TO
IN THE NEXT PHASE OF PAIN
STUDIES WE'RE DOING.
AND WITH RESPECT TO LIFESPAN, WE
WERE SHOCKED THAT WE DIDN'T SEE
ANY DIFFERENCES BETWEEN USE IN
ADULTS IN COLLABORATIONS WITH
DANNY, WE THOUGHT THE PREFRONTAL
CORTEX WOULD BE NECESSARY FOR
THIS.
AND WE ONLY STUDY UP TO 50 OR 60
TO BETTER TO LOOK AT LIFESPAN
PERSPECTIVE BUT WE HAVEN'T.
>> A FANTASTIC TALK, BRINGING
THE PSYCHOLOGICAL COMPONENT TO
PAIN AND JUST THE AMAZING AMOUNT
OF WORK IN SUCH A SHORT TIME.
I WANT TO CONGRATULATE YOU ON
YOUR TENURE AND YOUR TALK TODAY
AND PLEASE ALL OF US JOIN US IN
CONGRATULATING DR. LAUREN ATLAS.
[APPLAUSE]