behavioral assessment methods for rdoc constructs€¦ · a report by the national advisory mental...
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Behavioral Assessment Methods for RDoC ConstructsAugust 2016
NATIONAL INSTITUTE OF MENTAL HEALTH
A Report by the National Advisory Mental Health Council Workgroup on Tasks and Measures for Research Domain Criteria (RDoC)
Department of Health and Human ServicesPublic Health ServiceNational Institutes of HealthNational Institute of Mental Health
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TABLEOFCONTENTS
SectionI:ExecutiveSummary...............................................................................................................2
INTRODUCTION............................................................................................................................................2
THEWORKGROUPONTASKSANDMEASURESFORRDOC....................................................................................3
NIMH’sRequestforInformation..........................................................................................................3
WorkgroupCharge..............................................................................................................................4
SUMMARYOFRECOMMENDATIONSANDCONCLUSIONS......................................................................................6
GeneralIssues......................................................................................................................................6
Domain-specificTaskRecommendations............................................................................................7
NEXTSTEPS...............................................................................................................................................20
SectionII:DomainSpecificReports....................................................................................................22
NEGATIVEVALENCESYSTEMSFINALREPORT...................................................................................................23
POSITIVEVALENCESYSTEMSFINALREPORT....................................................................................................34
COGNITIVESYSTEMSFINALREPORT...............................................................................................................85
SYSTEMSFORSOCIALPROCESSESFINALREPORT..............................................................................................95AROUSALANDREGULATORYSYSTEMSFINALREPORT.....................................................................................105
AppendixA:RDoCMatrixDomain,ConstructsandSubconstructDefinitions....................................153
AppendixB:NAMHCRoster.............................................................................................................159
AppendixC:WorkgroupRoster........................................................................................................161
AppendixD:WorkgroupAgenda......................................................................................................163
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SECTIONI:EXECUTIVESUMMARY
Introduction
TheNationalInstituteofMentalHealth(NIMH)launchedtheResearchDomainCriteria(RDoC)in2009inresponsetothe2008NIMHStrategicPlan’scallfornewwaysofclassifyingmentalillnessesthatarebasedondimensionsofobservablebehavioralandneurobiologicalmeasures.RDoCisaresearchframeworkdesignedtointegratemanylevelsofinformation(fromgenomicstoself-report)tobetterunderstandthebasicdimensionsoffunctioningunderlyingthefullrangeofhumanbehavior,fromnormaltoabnormal.NIMHenvisionsthattheRDoCinitiativewilldeterminehowaclassificationapproachbasedonbiology,behavior,andcontextcanbeusefulformentaldisorders,thusinformingdiagnosticsystemsofthefuture.
Sinceitsinception,RDoChasprogressedasasignificanteffortfortheInstitute,impactingbasic,translational,andservices/interventionresearchpriorities.Initially,aseriesofcollaborativeworkshopswasheldinordertosummarizethestateoftheknowledgerelatedtofivemain“domains”anddefineassociatedconstructsforeach(seeAppendixA).ThecurrentRDoCframeworkconsistsofamatrixinwhichtherowsrepresentspecifiedfunctionalConstructs,conceptssummarizingdataaboutaspecifiedfunctionaldimensionofbehavior,characterizedinaggregatebythegenes,molecules,circuits,etc.,whichimplementit.Constructsareinturngroupedintohigher-levelDomainsoffunctioning,reflectingcontemporaryknowledgeaboutmajorsystemsofcognition,motivation,andsocialbehavior.Initspresentform,therearefiveDomainsintheRDoCmatrix:NegativeValenceSystems,PositiveValenceSystems,CognitiveSystems,SystemsforSocialProcesses,andArousal/RegulatorySystems.ThematrixcolumnsspecifyUnitsofAnalysisusedtostudytheConstructs,andincludegenes,molecules,cells,circuits,physiology,behavior,andself-reports.Thematrixalsohasaseparatecolumntospecifywell-validatedparadigmsusedinstudyingeachConstruct.Theseparadigmsmayberelevantformorethanoneunitofanalysisandratherthanlisttheminseparatecolumns,theyareincludedundertheParadigmsheading.Inthebodyofthematrixarespecificelementswhichareempiricallyassociatedwiththeconstructandaregroupedundertheappropriateunitofanalysis.
TheRDoCmatrixprovidesoneframeworkfororganizingNIMHresearchefforts,freeingscientistsfromtraditionalcategoriesthatareoftenheterogeneousandoverlapping.RDoCaimstosupportresearchthatconsidersmentalillnessesintermsoffundamentalbehavioral-neuralsystems(e.g.,fearorworkingmemory)ratherthantraditionaldiagnosticcategories.Thelong-termgoalistodevelopascientificbasethatcaninformfutureneuroscience-baseddiagnosticsystemsformentalillnesses.TogenerateasystematicRDoCdatabaseforthispurpose,itisimportanttodevelopasetofparadigmsandmeasuresthataregenerallyacceptedbythefieldandwhichcanfacilitatecomparisonsacrossstudiesandsharingofdata.However,ifNIMHprematurelyestablishesforabatteryofaffective,behavioral,andcognitivetasksforuseinRDoCresearch,itrunstheriskofhamperingfuturemethodologicalinnovationandrevisionstotheRDoCconstructs,whichwouldhavedeleteriouseffectsonthelong-termdevelopmentofRDoC.Areasonablecompromiseistoestablishasetofstandardizedparadigmsandmeasures
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whichareappropriateforassessingRDoCconstructs,butwhicharenotrequiredtobeusedinRDoCresearch.SuchalistwouldofferthefieldsomestandardizationthatcanfosterdatasharingthroughtheRDoCDatabase(RDoCdb),butwouldrequireregularrevisioninordertoincorporatenewdevelopmentsandfindings.
Toinitiatethedevelopmentofstandardizedparadigmsandmeasures,NIMH’sRDoCUnitproposedtheconceptclearance,FirstGenerationResearchDomainCriteria(RDoC)MeasurementElements,totheNationalAdvisoryMentalHealthCouncil(NAMHC;seeAppendixB).TheCouncilapprovedthisconceptatitsMay29,2015meeting.Theaimofthisinitiativewastosupporttheidentificationoftwotofourparadigmsand/ormeasuresthatwouldbeoptimalforeachRDoCconstruct.Thesemeasureswouldprovideresearchersachoiceamongagroupofvettedelements,whilestillmaintainingadegreeofstandardization.Identifyingconstructsforwhichnoappropriatemeasuresexisthelpstoidentifyareasinneedoffurtherassessmentdevelopment.
TheWorkgrouponTasksandMeasuresforRDoC
DuringtheFebruary4,2016NAMHCmeeting,NIMHActingDirectorBruceCuthbert,Ph.D.,announcedtheformationoftheWorkgrouptoimplementtheFirstGenerationRDoCMeasurementElementsconcept.Agroupof34researchersfrom34uniqueinstitutionswasestablished(seeAppendixCforaroster),witheachparticipantagreeingtoparticipateinonedomain-specificsubgroup.Aleaderwasassignedforeachdomainsubgroup,andtookontheresponsibilityofleadingthediscussionsandhelpingtoassembleandcoordinatethedomainsubgroup’sfinalrecommendations.TheNationalAdvisoryMentalHealthCouncilWorkgrouponTasksandMeasuresforResearchDomainCriteriaconvenedanin-personmeetingonApril5and6,2016(seeAppendixDforthemeetingagenda)attheNeuroscienceCenterinRockville,Maryland.DeannaBarch,Ph.D.,ProfessoratWashingtonUniversityandMariaOquendo,M.D.,ProfessoratColumbiaUniversity,co-chairedtheWorkgroup.
NIMH’sRequestforInformationInpreparationfortheworkgroupmeeting,NIMHpublishedarequestforinformation(RFI)titled“BuildingaSetofRecommendedTasksandMeasuresfortheRDoCMatrix”onMarch25,2016,toseekinputfromthefield.ResponsestotheRFIweredueApril22,2016.ThroughtheRFI,NIMHgatheredinformationaboutexistingtasksandmeasurementtoolsthatwererecommendedforinclusionintheRDoCmatrix,aswellasgeneralsuggestionsaboutthemostimportantcriteriaforconsiderationinselectingcandidatetests.
AsofMay10,2016,NIMHreceived60responses.Ofthese,asubsetof42wereclassifiedasrelevantandontopic.Sevenofthesesuggestedgeneralcriteriatoconsiderwhenselectingatask.Theremainingresponsesincludedrecommendationsforspecifictasks,acrossallfivedomains.
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WorkgroupChargeThechargetotheWorkgroupwastorecommendasetoftwotofourtasksforeachconstructthatmeetallormanyofthefollowingcriteria.ThesecriteriaweredevelopedbasedondiscussionsamongtheRDoCworkgroupmemberspriortothestartofthemeeting,andmodifiedthroughinformationgainedfromtheRFIandfromdiscussionsatthestartofthein-personCouncilworkgroupmeeting.
• HowstrongistheevidencethatthetaskprovidesavalidmeasureoftheRDoCconstruct?• Howgoodistheevidenceaboutthepsychometriccharacteristicsofthetask(e.g.,internal
reliability,test-retestreliability,floorandceilingeffects,practiceeffects,availabilityofalternateforms,andlongitudinalstability)?
• Isthetaskfreefromfloor/ceilingeffectssothatitcanbeusedacrossindividualswiththefullrangeofperformance/impairmentonthetasks?
• Areparametersforadministeringthetask(e.g.,numberoftrials,stimuluscharacteristics,andprimarydependentmeasure)standardizedonanempiricalbasis?
• Towhatextentisthetask(ordifferentversionsofthetask)suitableforuseacrosslaboratory-basedstudies,clinicaltrials(asameasureoftargetengagementorclinicaloutcome),and/orhigh-throughputscreeningsettings?Isthetasksuitableforuseinhumansubjectsinavarietyoflaboratoryenvironments?Isthetaskfeasibleforadministrationacrosssites?Whatworkisneededtomakethetaskreadyforuseinclinicaltrials?
• Canthetaskbeused(oradaptedforuse)withchildrenandotherspecialpopulations?Canitbeusedacrossdifferentculturalsettings?
• Canthetaskbeusedasastand-alonebehavioraltask?• Areadequatenormativedataavailableacrossage,gender,education,ethnicity,and
socioeconomicstatus?• Isthetaskwidelyusedcurrentlyorhasitsusebeenlimitedtoafewresearchgroups?• Isthetasksensitivetowithin-personchange?• Aretherelationshipsbetweentaskperformanceandclinicalfeature(s)known?• Isthetaskfreelydistributed(i.e.,notcopyrighted)?• DoesthetaskassessmultipleRDoCconstructsorisitspecifictojustone?Ifitassesses
multipleconstructs,doesitallowforunambiguousconclusionsaboutthetargetedconstruct?
Duringthedomain-specificbreakoutsessions,theworkgroupmemberswereaskedtorateeachproposedtaskormeasurementtooloneachcriterionusingascaleof1to5(1=noevidence,3=someevidence,5=strongevidence),inordertofacilitatedirectcomparisonsamongtaskcharacteristics.Otherproposedtaskcharacteristicsconsideredimportantwhenevaluatingatask,butnotrequiredforbehavioralmeasuresofRDoCconstructs,are:
• Canthetaskbeusedwithmethodstointerrogatebraincircuitry(e.g.,functionalmagneticresonanceimaging[fMRI]andEEG)?
• Canthetask(oritsanalog)beusedinanimals?Isananimalversionavailable?• Aretherelationshipsbetweentaskperformanceandneuralsignal(s)known?
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IndiscussingtheWorkgroup’schargeandcriteriafortasknomination,themembersoftheworkgroupdevelopedthefollowingsuggestions:
• Donotspendtimeattheworkgroupmeetingrevisitingtheorganizationofthematrixorthedefinitionsoftheconstructs.Suggestionsforchangesarewelcomebutthefocusofthediscussionsshouldbeonmeasuresfortheconstructsastheyarecurrentlydefined.
• Whereverpossible,themeasuresshouldallowforbehavioralassessment,asopposedtofocusedsolelyonbiologicalsignals(e.g.,neuroimaging).However,itwasrecognizedthatsomeconstructs(e.g.,sleepcycles)cannotbemeasuredbehaviorally.NIMHwillobtainrecommendationsfortasksandmeasuresrelatedtolevelsofanalysis—includingelectrophysiologyandneuroimagingmeasures—infuturemeetings.
• Whenchoosingamongmeasures,ataskthatrelatestoclinicalfeatures(particularlyfunctionalstatus)ispreferred.
• Regardingtheuseoradaptationoftasksforchildrenandotherspecialpopulations,workgroupmembersshouldconsiderwhetherthetestissensitivetonormativedevelopmentalchange.Withataskthatbothchildrenandadultscanperform,itwouldbehelpfultobeabletodeterminewhetherthegroupsareusingthesameordifferentstrategies.
• Workgroupmembersshouldconsiderthatsomemeasuresareinfluencedbyculture.• Workgroupmembersshouldconsidertheacceptabilityoftaskstosubjects.Somemightbe
toodifficultandperceiveddifficultymayvaryacrosspopulationgroups.• Thenewwebdesignofthematrixallowsfortheadditionofinformation(e.g.,referencesto
publications)aboutelements.Therefore,workgroupmembersshouldidentifyinformationabouttasksthatcanbeaddedtothematrix.
• Whennominatingatask,theworkgroupshouldnotewherepossible:
– theparticularpsychometricpropertiesofthetaskorparadigm(whereinformationisavailable)andthesubpopulationsthathavebeentested;
– whetherthetaskmeasuresastateortrait;– theappropriateuseofthetask(e.g.,whetheritissuitableforlongitudinalresearch
versussingleadministration);– whethertheparametersforadministeringatask(e.g.,numberoftrials,stimulus
characteristics,andprimarydependentmeasures)havebeenstandardizedbasedonempiricalevidence;
– variationintheparametersneededtoobtainthedesiredlevelofsensitivityacrosspopulations;and
– thesettingsinwhichthetaskcanbeused(e.g.,laboratoryorclinical).
ThetaskscurrentlylistedintheRDoCmatrixprovidedastartingpointfortheworkgroup’sdeliberations.Membersoftheworkgroupwerealsoencouragedtoidentifyothertaskswhichmaybewell-suitedforspecificconstructsandtoidentifyconstructsforwhichnewtasksareneeded.Theworkgroupwasinformedthatasuccessfulreportwouldprovide(1)alistofcurrently-availabletasksandmeasuresthatarerecommendedforinclusionintheRDoCbattery,(2)alistoftasksthatcouldbeappropriateforinclusionbutareinneedoffurther
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optimizationandasummaryoftheworkneededinordertooptimizethem,and(3)alistofconstructsforwhichnoappropriatetasksareavailable.Workgroupmemberswerealsoaskedtoprovidealistofparadigmsthatwereconsideredforinclusionbutnotrecommended,includingtherationaleforexclusion.
Theintentoftheserecommendationsfromtheworkgroupisnottobeoverlyprescriptive;thegoalistofacilitateuseofcommondataelementswherefeasible.Thelistofrecommendedtaskswillbedynamic,asresearchersinthefieldwillbeabletomakethecaseforothertasksormeasuresthatalsomeetthecriteria.
SummaryofRecommendationsandConclusions
GeneralIssuesIntheirdiscussionsoftasksandmeasures,alldomainsubgroupsencounteredaparticularchallenge:theabsenceofpsychometricdata.Formanyoftherecommendedtaskstherearenonormativedata.Thefieldwouldbenefitfromadditionaldata,andfurtheranalysis,inordertounderstandthebasicpsychometricpropertiesofpopulartasksincurrentuse.Similarly,manyofthetasksdonothaveempiricallyderivedadministrationparameters,andlackstandardizationacrosssites.Furtheroptimizationandstandardizationtoensurethatalllabsusingacertaintaskaremeasuringthesamephenomenonwouldbeuseful.
Itisalsonotedthatanumberofthedomainsubgroupsfocusedonbehavioralmeasuresanddidnotconsiderself-reportmeasures,inlargepartbecauseoftimeconstraintsattheworkgroupmeeting.Thelackofself-reportrecommendationsshouldnotbeinterpretedtomeanthattheworkgroupconsideredthesetobeinvalidornotrecommended,butperhapsshouldbethefocusofafuturemeeting.
Anotherissuethatcameupinmanydomainsubgroupswasthequestionofhowtoaddressregulatoryprocesses,includingemotionregulation.Emotionregulationiscurrentlyconsideredtobeanimplicitcomponentofanypertinentconstruct;forexample,controloffearbehaviororcontrolofimpulsivebehavior.Thus,emotionregulationwasnotoriginallydefinedasadistinctconstructinanydomain.However,thedomainsubgroupssuggestedthatitmayneedamoreexplicitroleinthematrix.Assuch,thedomainsubgroupssuggestedthatmorefocuseddiscussionofmethodsforassessingthiscriticalconceptwereneeded.
Lastly,manydomainsubgroupsnotedthattheorganizationofdomains,definitionsoftheconstructs,oroverallscope/coverageofthefieldwouldbenefitfromupdating.Somedomainsubgroups(i.e.,PositiveValence)madespecificsuggestionsastohowtochangetheDomain,whereasotherdomainsubgroups(i.e.,NegativeValence)simplynotedthattheorganizationanddefinitionsweredifficult,butworkedwithintheguidelinestorecommendtasksfortheexistingmatrix.Itisrecommended,however,thatthedefinitionsandorganizationsoftheconstructsbeevaluatedinafuturemeeting.DuringtheMay26,2016NAMHCmeeting,NIMHActingDirectorBruceCuthbert,Ph.D.,announcedtheformationofanewWorkgrouponRevisionstotheRDoCMatrix.ThechargetothisgroupwillbetoadvisetheNIMHon
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modificationstotheRDoCmatrix,includingadditionofnewdomainsandconstructs.ManyoftherecommendationsaboutdomainorganizationmadebytheworkgrouponTasksandMeasuresforRDoCwillbepassedalongtothisnewlyformedworkgroupfortheirdiscussion.
Domain-specificTaskRecommendationsEachofthedomainsubgroupsprovidedanextensivefinalreport.Hereweprovideexecutivesummaries.ThefullreportscanbefoundinSectionII:DomainSpecificReports.
NegativeValenceSystems(SeeSectionIIforfullreport)TheNegativeValenceSystemssubgroupnoteddifficultieswiththewaythedomainwasdefinedandorganized.Theysuggestthatseveraloftheconstructdefinitionsdonotlendthemselvestoalaboratorymeasurementmodelthatwouldelicittheindividualdifferencesofinterest.Forexample,manyoftheirrecommendationsforSustainedThreatandLossactuallyinduceanalogsfortheaffectivestate,ormeasuredownstreamconsequences,anddonottapthedefinedconstructdirectly.Additionally,theysuggestthatthedomainislackingincoverageacrossthetopicarea,andshouldmoreexplicitlydovetailwithPositiveValenceSystems,asthereisagreatdealofoverlapinthetasksandmeasuresthatcouldbeused.Theysupporttheadditionofconstructsof“emotionallability”,“pain”,and“affectivedecisionmaking”.
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NegativeValenceSystemsRecommendedTaskParadigms
Construct/Sub-construct Task Keyreferences
1.AcuteThreat
TrierSocialStressTest Kirschbaumetal.1993Allenetal.2014
BehavioralApproachTest nonelisted
ColdPressorTest Edelsonetal.1986Velascoetal.1997Rolkeetal.2006
CO2Challenge nonelisted
StrangerTests Bussetal.2003Pfeiferetal.2002
FearConditioningTasks Norrholmetal.2008Zeidanetal.2012
2.PotentialThreat
NoShock,PredictableShock,UnpredictableShock(NPUThreatTask)
Schmitzetal.2012
3.SustainedThreat
None(seefullreportfordiscussionofwhynonewererecommended)
4.Loss(analogofresponsetoloss
Sadnesselicitingfilmclips(butonlywithw/immersioninstructionsandfacialexpressionormoodratingsasdependentvariablesofinterest)
Samsonetal.2015Joormannetal.2007
5.FrustrativeNonreward
PointsSubtractionAggressionParadigm(PSAP)
Cherek,1981Genioleetal.2016
LaboratoryTemperamentAssessmentBatterytasksofBoxEmptyandTransparentBox
Gagneetal.2011
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NegativeValenceSystemsRecommendedSelfReportMeasures
Construct/Sub-construct Task Keyreferences
1.AcuteThreat
SubjectiveUnitofDiscomfortScore(SUDS) Wolpe,1990Kaplanetal.1995
FearSurveySchedule Wolpe&Lang,1977
2.PotentialThreat
IntoleranceofUncertaintyScale(12itemversion)
Carletonetal.2007
BehavioralInhibitionScale(BIS) Carver&White,1994
FearofNegativeEvaluationScale Watson&Friend,1969
AnxietySensitivityIndex Tayloretal.2007
LifeEventsandDifficultiesSchedule(LEDS) Brown&Harris,1978
3.SustainedThreat
YouthLifeStressInterview Rudolph&Flynn,2007
ChildhoodTraumaQuestionnaire Bernstein&Fink,1998
LEDSdifficulties Brown&Harris,1978
TraumaticEventsScreeningInventory(TESI) Ippenetal.2002
RiskyFamilies Tayloretal.2004
StressandAdversityInventory(STRAIN) Slavich&Epel,2010
4.Loss(analogofresponsetoloss)
LEDS(socialexperienceoflossandpotentialthreat)
Brown&Harris,1978
STRAIN Slavich&Epel,2010
5.FrustrativeNonreward
FrustrativeNonrewardResponsivenessSubscale
Wrightetal.2009
QuestionnaireofDailyFrustrations Baarsetal.2011
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PositiveValenceSystems(SeeSectionIIforfullreport)Thelistofsuggestedtasksandmeasuresforthisdomainreflectsaslightregroupingandrenamingoftheconstructstomoreclearlymatchtheexistingempiricalliterature,whichthePositiveValenceSystemssubgroupsuggestsreducespotentialredundanciesacrosstheconstructs,andisolates“purer”constructs.Theypropose3totalConstructs;“RewardResponsiveness”,“RewardLearning”and“RewardValuation,”eachwith3newsub-constructs.Thedomainsubgroupdiscussedthefactthatmanytasksthatweredevelopedearlyandhavebeenwidelyusedoftenconflatemultiplesub-constructs.Thus,manyofthesetasksmightsubsumedifferentsub-constructsinthesametask.Newparadigmshavelessaccumulateddatabutaremorepreciseindifferentiatingsub-constructs.Aswiththeotherdomains,theworkgroupalsonotedthatmuchmoredataareneededonpsychometricsandnormsformostifnotallofthetasks.Additionally,thegroupsuggestedthattheregulationofthePositiveValenceSystemsconstructs(e.g.,modulationofPVSconstructsbyhomeostaticdriveslikehunger,sleep,thirst,sex)wouldinvolveprocessesthatarebettercapturedbyCognitiveSystemsandArousalandRegulatorySystems,andsotheydidnotincludetasksthatprobedtheseregulatoryprocessesintheirdeliberations.
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PositiveValenceSystemsRecommendedTaskParadigms
Construct/Sub-construct Task Keyreferences
1.RewardResponsiveness
1.1.InitialResponsetoReward
SimpleGuessingTask Delgadoetal.2000Carlsonetal.2011
1.2.RewardAnticipation MonetaryIncentiveDelayTask Knutsonetal.2000
1.3.RewardSatiation Fixed-ratioSatiationSchedule Sherman&Thomas1968
2.RewardLearning
2.1.Habit DevaluationTask Gillanetal.2011
HabitTask McKimetal.2016
HabitLearningTask Tricomietal.2009
2.2.ProbabilisticandReinforcementLearning
ProbabilisticRewardTask Pizzagallietal.2005
PavlovianConditioning O’Dohertyetal.2004
Driftingdoublebandit Dawetal.2011
ProbabilisticStimulusSelectionTask Franketal.2004
2.3.RewardPredictionError RutledgePassiveLotteryTask Rutledgeetal.2010
Driftingdoublebandit Dawetal.2011
3.RewardValuation
3.1.Reward(probability) ProbabilityChoiceTask Levyetal.2010
WillingnessToPayTask Beckeretal.1963
3.2.Delay DelayedDiscountingTask Kable&Glimcher2007Johnson&Bickel2002Green&Myerson2004
3.3.Effort EffortExpenditureforRewardTask Treadwayetal.2009
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CognitiveSystems(SeeSectionIIforfullreport)TheCognitiveSystemsDomainsubgroupgroupdiscussedthefactthatmanycognitiveconstructsoverlap(forexample,workingmemoryandcognitivecontrol),andthatthisisthenatureofcognitionandtosomeextentunavoidable.ThereisadditionaloverlapbetweentheCognitiveSystemsDomainandotherdomains(forexample,vigilanceisanaspectofattentionandalsoanindexofarousal.)Thedomainsubgroupalsonotedthatsomekeycognitiveconstructswerenotcurrentlyrepresentedinthematrix,suchasreasoningandinference.ThedomainsubgrouphassuggestedanupdateoftheAttentionconstruct,inlightofcurrentworkincognitiveneuroscienceandsuggeststhreesubconstructs,“Controlledvs.AutomaticAttention,”“CapacityandInterferenceControl,”and“Vigilance(SustainedAttention).”Anotherobservationwasthattheconstruct“LanguageBehavior”waslesswellelaboratedthanotherconstructs.Thisdomainsubgroupfelt,giventhespecializednatureofthefieldoflinguisticsandtheinteractionsbetweenlinguisticandcognitivesystems,thatidentifyingsubconstructsandparadigmsfromthisconstructwouldbebestaccomplishedbyanewsubgroupwithmoreexpertiseinthearea.
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CognitiveSystemsRecommendedTaskParadigms
Construct/Sub-construct Task Keyreferences
1.Attention
1.1.Overt/Covert Spatialandnon-spatialcuingtasks Carteretal.1992
AttentionNetworksTask(ANTS) Macleodetal.2010
Visualsearchparadigm Goldetal.2007
1.2.CapacityandInterferenceControl
Attentionalblinkduringrapidserialvisualpresentation
Mathisetal.2011
Dualtaskparadigms Nuechterleinetal.2006
1.3.Vigilance Taskswith‘catch’trials(changedetectionworkingmemory,perceptualthresholdeffects)
Barchetal.2011
Mind-wanderingtasks Smallwood&Schooner,2015
2.Perception
2.1.Visual Contrast-ContrastTask Barchetal.2011
JitteredOrientationvisualintegrationtask(JOVI)
Silversteinetal.2011
3.DeclarativeMemory
RelationalandItemSpecificEncodingTask(RISE)
Raglandetal.2012
MnemonicSimilarityTest Bakkeretal.2008
4.CognitiveControl
4.1.GoalSelection,Updating,RepresentationandMaintenance
ContinuousPerformanceTests(AXandDPX)
Lopez-Garciaetal.2015
Preparingtoovercomeprepotencytask(POP)
Snitzetal.2005
4.2ResponseSelection,ResponseInhibition/Suppression
Go/No-gotasks Boucheretal.2007
StopSignalTasks Luijtenetal.2014
4.3PerformanceMonitoring FlankerTaskversions None
SimonTaskversions None
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Construct/Sub-construct Task Keyreferences
StroopTaskversions Kernsetal.2004
5.WorkingMemory
5.1.ActiveMaintenance MatchtoSample Horwitz&Tagaments,1999
Sternbergtasks Nelsonetal.2003
ChangeDetection Barchetal.2011
ContinuousPerformanceTests(AXandDPX)
Lopez-Garciaetal.2015
5.2FlexibleUpdating NBacktasks Jonidesetal.2008
Self-orderedPointing Gillett,2007
5.3LimitedCapacity ChangeDetection Barchetal.2011
5.4InterferenceControl Nbacktasks Jonidesetal.2008
Sternbergtasks Nelsonetal.2003
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SystemsforSocialProcesses(SeeSectionIIforfullreport)TheSystemsforSocialProcessessubgroupsuggestedsomechangestothedomain’sorganization,andsuggestedadding“RejectionSensitivity”and“SocialMotivation”assubconstructsundertheAffiliationandAttachmentconstruct.Thegroupnotedthatthe“SocialCommunication–ProductionofFacialCommunication”subconstructwouldbenefitfromfurtherdevelopmentregardingmethodsofelicitingemotionsandmeasuringfacialexpressions.Beyondfacialcommunication,thereisasignificantneedtodeveloptechniquesandinstrumentsthatcapturethedimensionalityoffunctioningacrossthelifespan,aswellasinstrumentsthatmaximizeecologicalvalidity.
ThedomainsubgroupstronglyrecommendedeliminatingtheStrangeFaces(separation-reunion)task,theStillFace,andtheFordCorollaryDischargeparadigmsfromthelistofparadigmscurrentlylistedintheRDoCmatrix.Thegroupidentifiedsignificantproblemswiththesetasks;howeverthisdoesnotmeantheyendorsealloftheremainingtasksinthecurrentmatrix.
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SystemsforSocialProcessesRecommendedTaskParadigms
Construct/Sub-construct Task Keyreferences
1.AffiliationandAttachment
1.1RejectionSensitivity Cyberball
Hartgerinketal.2015Bolling,2011
1.2SocialMotivation One-armedBanditTask Linetal.2012
2.SocialCommunication
2.1.ReceptionofFacialCommunication
ER-40–PennEmotionRecognitionTest Erwinetal.1992
GazeCuing Gross&Levenson,2008
2.2.ProductionofFacialCommunication
None
2.3.Non-facialcommunication(mergedreceptionandproduction)
TASIT1 McDonaldetal.2003
3.PerceptionandUnderstandingofSelf
3.1.Agency None
3.2.SelfKnowledge Self-ReferentialMemoryParadigm Kelley,etal.2002
4.PerceptionandUnderstandingofOthers
4.1.AnimacyPerception PointLightDisplaysofBiologicalMotion
Bjornsdotteretal.2016
4.2.ActionPerception HowpartofHow/Whytask Spunt&Adolphs,2014
4.3.UnderstandingMentalStates HintingTask Corcoran&Frith,2003
ReadingtheMindintheEyes Vellanteetal.2013
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SystemsforSocialProcessesRecommendedSelfReportMeasures
Construct/Sub-construct Task Keyreferences
1.AffiliationandAttachment
1.2SocialMotivation MultidimensionalScaleofPerceivedSocialSupport
Zimetetal.1988
2.SocialCommunication
2.3.Non-facialcommunication(mergedreceptionandproduction)
SocialResponsivenessScale Constantinoetal.2003
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ArousalandRegulatorySystems(SeeSectionIIforfullreport)TheArousalandRegulatorySystemssubgroupworkeddirectlyfromconstructsalreadydefinedintheRDoCmatrix,anddidnotsuggestanyrevisionsoreditstothoseconstructs.Thegrouppointedoutsomeissueswiththegeneralconceptof“arousal,”indicatingthatitisnotwell-definedinthematrix,andthatthetermgenerallycutsacrossmanyconstructsindomains,includingattention,motivation,andanxiety,amongothers.Thegroupalsonotedthattheconstructsaresubservedbyawidearrayofneurobiologicalprocessesandfunctions,whichaddstothecomplexityoftryingtodisentanglearousalfromotherdomainsofthematrix.
Theynotethatmanyofthemeasuresthatwereconsidereddonothaveagreeduponstandardsforadministrationoranalysis,andmostneedmorenormativedata.Thereareseveralrecommendedmeasuresandtasksthatincludebothautonomicnervoussystemandthecentralnervoussystem.Thegroupsuggeststhatpolysomnography,orsleepEEG,isaveryusefulandwidelyusedtoolfortheSleep-Wakefulnessconstructandamuchbettermeasurethanhomerecordings,butacknowledgethatitistimeconsumingandexpensive.Lastly,thegroupnotesthattherearenotmanygoodself-reportmeasuresinthisdomainanddevelopmentworkonthesemaybeofbenefittothefield.
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ArousalandRegulatorySystemsRecommendedTasks
Construct/Sub-construct Task Keyreferences
1.Arousal
HeartRateVariability(HRV)* Beauchaineetal.2015
ElectrodermalResponding(EDR)* Boucseinetal.2012
Pupillometry* Beattyetal.,2000
CardiacPre-ejectionPeriod(PEP)* Sherwoodetal.1990
PsychomotorVigilanceTask† Basneretal.2011
2.Sleep-Wakefulness
Latencytopersistentsleep(LPS),Waketimeaftersleeponset(WASO),Totalsleeptime(TST)
‡
Iberetal.2007
SleepSpindles‡ Iberetal.2007
Non-REMSleep,SleepEEGSlowWaveActivity
‡
Dijketal,1993
MultipleSleepLatencyTest(MSLT)‡ Littneretal.2005
InsomniaSeverityIndex§ Bastien,2001
FingerTappingMotorSequenceTask(MST)
Karnietal.1998
3.CircadianRhythms
DimLightMelatoninOnset(DLMO) Burgessetal.2015
LongitudinalActigraphy Briscoeetal.2014
Morningness-EveningnessQuestionnaire(MEQ)
§
HorneandOstberg,1976
MunichChronotypeQuestionnaire§ Roennebergetal,2003
*Autonomicmeasure†Cognitivemeasure‡Allmeasuredbypolysomnography§Self-Reportmeasure
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NextSteps
BoththeproceedingsofthisworkshopandtheadvancesinthefieldoverthepastseveralyearssuggestanumberofimportantnextstepsintheRDoCInitiative.Weoutlinethembrieflyhere:
CriticalEvaluationofCurrentRDoCDomainsandConstructs:ThefieldislearningagreatdealaboutthetypesofdomainsandconstructsincludedinRDoCasthepaceofresearchontheseconstructshasevolved.Thedomainsubgroupreportsmakeitclearthatchangesarelikelyneededtosomeofthedomainsandconstructsgivennewknowledgeabouttheirvalidityandtheirorganization.SuchchangesarelikelytomaketheRDoCframeworkmoreusefulintermsofgeneratinginformationaboutputativebrain-behaviordimensionsrelevanttopsychopathology.Thus,anewroundofworkshopstoevaluateandinstantiatethesechangeswouldbeuseful.Aswithworkshopsonotherlevelsofanalysis,shouldsuchworkshopsbeenvisioned,wewouldrecommendanearlystarttogatheringinformationfromthefield,ideallythroughtheuseofamorefocusedsurveyinlieuofanRFIapproach,whichthoughhelpful,ismoregeneral.
DevelopmentofNewRDoCDomainsorConstructs:Resultsofthedomainsubgroups’workindicatesomeareaswherenewconstructsordomainsareneeded,forexample,emotionregulation.ThiscriticallyimportantconstructisnotcurrentlywellcapturedinanyexistingRDoCdomain,andfurtherconsiderationcouldhelpdetermineifitwouldbebeneficialtomodifythecurrentviewofemotionregulationasimplicitinrelevantconstructs(e.g.,fear,reward-relatedactivity,lackofcognitivecontrol).Itisessentialtodevelopaprocessbywhichnewdomainsorconstructscouldbeproposedandtheevidencefortheirvaliditysystematicallyevaluated.Suchaprocesswouldbenefitfromexplicitconsiderationofrecommendedtasksandparadigmsacrossdifferentlevelsofanalysis,similartotheprocessundertakenbythecurrentworkgrouptoidentifybehavioraltasksandparadigms.
Relatedtobothoftheserecommendations,anewCouncilworkgroupthatwilladviseNIMHregardingchangesandupdatestotheRDoCmatrixwasestablishedinMay2016andwillhaveitsfirstmeetinginSeptember2016.
AnalogousProcessforOtherLevelsofAnalysis:Thisworkgroupfocusedonmeasureswith“behavioral”outputs,primarilyduetotheneedtofocustheevaluationeffortstomeettimeandpracticalityconstraints.However,asnotedinseveraldomainsubgroupreports,insomecases,adifferentlevelofanalysismayeitherbetheonlywaytomeasureagivenconstruct,ormaybeabetterwaytomeasurethatconstruct.Assuch,additionalworkgroupsthatgothroughasimilarprocesswithmeasuresatotherlevelsofanalysis,suchasneuroimagingmeasuresand/orperipheralphysiology,willbeessential.Similarly,fewdomainsubgroupshadtimetosystematicallyevaluateself-reportmeasuresformanyconstructs,andaworkgroupspecificallyfocusedonself-reportwouldalsobebeneficial.Shouldsuchworkshopsbeenvisioned,wewouldrecommendanearlystarttogatheringinformationfromthefield,ideallythroughtheuseofamorefocusedsurveyinlieuofanRFIapproach,whichthoughhelpful,ismoregeneral.
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DevelopmentalConsiderations:Thefieldisincreasinglyfocusedonearlydetectionandidentification.Toaccomplishthisgoal,researchonRDoCrelatedconstructsneedstobeconductedinchildren,includingveryyoungchildren.Forexample,theNegativeValenceSystemssubgroupwasabletoprovideastrongintegrationofdevelopmentalconsiderations.Itishighlylikelythatmanypromisingparadigmsvalidatedinadultswillonlyworkeffectivelywithchildreniftheyareeithermodified(simplerinstructionsortasks,developmentallyappropriatematerials,etc.),oruseadifferentapproachtomeasurement(observationalmeasures,etc.).Suchdevelopmentalconsiderationswillcontinuetolagbehindifnotspecificallyprioritized,eitherthroughfocusedworkshopsorthroughresearchwiththespecificgoalofmakingdevelopmentallyappropriatemodificationstoparadigmsusefulinadultpopulations.SimilarconcernsmayarisewhenextendingRDoCrelatedworkintogeriatricpopulations,whereothertypesoflifespanappropriatetaskmodificationsmaybeneeded.
StandardizationandPsychometricEvaluation:Afewoftherecommendedtasksdescribedabovehavestandardizedversionswithatleastsomedataabouttheirpsychometricproperties.However,everydomainsubgroupnotedthatevenformanypromisingparadigmsorclassesofparadigms,littlestandardizationofadministrationparametersexistsandinmanycases,littlepsychometricdataexist.Inordertoachievethecommondataelementsgoal,itwillbecrucialfortheretobe:(1)standardizationwithappropriateattentiontopotentialvariationneededasafunctionofpopulationand(2)evaluationofthepsychometricpropertiesofthesetasks.Itisunlikelythatcommondataelementswillbeadoptedformanyconstructsuntilthisworkisdone.Finalmeasuresthatarewidelyandfreelyavailableonflexibleandeasy-to-useplatformswillfacilitatedatasharingandintegration,buttheymustbeundergirdedbythiskeygroundwork.
Insummary,developmentoftheRDoCsystemwillrequirefocusedattentiontoensurethatthedomainsandconstructsremaininformedbynewevidenceandarerefinedasmoreworkisconducted.Thekeygoalofidentifyingcommondataelementstofacilitatedatasharingandcomparisonsacrosslaboratorieswillnecessitatesimilarprocessestotheonesdescribedherefordifferentlevelsofanalysis.Althoughincremental,suchstepsarecriticaltoenhancingthequalityofdataavailabletoaddresstheunderlyingneurobiologicalmechanismsofbehaviorrangingfromnormaltoabnormal.
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SECTIONII:DOMAINSPECIFICREPORTS
Thefollowingreportsweregeneratedbyeachdomainsubgroup,basedontheirdiscussionsbothatthemeeting,andafterthemeetingwascomplete.
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NegativeValenceSystemsFinalReport
C.EmilyDurbin,Ph.D.,IanH.Gotlib,Ph.D.SheriL.Johnson,Ph.D.,MercedesPerez-Rodriguez,M.D.,Ph.D.,StewartShankman,Ph.D.(chair)
I.GENERALCOMMENTSTheNVSsubgroupwaschargedwithdevelopingalistforthefiveconstructslistedwithinNVSdomain-(1)AcuteThreat;(2)PotentialThreat;(3)SustainedThreat;(4)Loss;and(5)FrustrativeNonreward.Giventhischargeanddiscussionattheoutsetofthemeeting,theNVSgroupdecidedtoworkstrictlyfromtheconstructsandexistingdefinitionslistedintheRDoCmatrix(http://www.nimh.nih.gov/research-priorities/rdoc/constructs/rdoc-matrix.shtml)andnotattempttorevise,add,orclarifytheconstructsinthematrix.
AfirstimportantissuethatsignificantlyguidedtheNVSsubgroup’sdiscussionwasthefactthatforseveralconstructs,thecommitteechargeprovedtobedifficult;thedefinitionsoftheconstructsdidnotalwayslendthemselvestoameasurementmodelinwhichtheelicitingcontextsfortheindividualdifferencesofinterestcouldberecreatedviaspecificlaboratoryorinvivoparadigms.Forexample,SustainedThreat(NVSconstruct#3)isdefinedas“Anaversiveemotionalstatecausedbyprolonged[i.e.,weekstomonths]exposuretointernaland/orexternalcondition(s),state(s),orstimulithatareadaptivetoescapeoravoid.”Wefeltthattherearenoparadigmsthatcouldbeusedethicallytoassessdirectlytheeffectsofsustainedthreatinhumans.Weacknowledgethattherearereal-lifesituationsthatmightbeusedasquasi-experimentalparadigmstoassesstheeffectsofsustainedthreatinhumans(e.g.,combatexposure,naturaldisasters).Inaddition,whilewecouldidentifyparadigmsthatassess‘downstreamconsequences’ofsustainedthreat(e.g.,attentionalvigilancetoemotionalstimuli),thespecificityoftheseconsequencestosustainedthreat(asopposedtoacutethreat,potentialthreat,orthreatingeneral)wasnotclear.ThegrouphadasimilardifficultywiththeconstructofLoss.LossisdefinedintheRDoCmatrixas“astateofdeprivationofamotivationallysignificantcon-specific,object,orsituation…andmayincludepermanentorsustainedlossofshelter,behavioralcontrol,status,lovedones,orrelationships.”Wefeltthatthisspecificaffectivestatecouldnotbeinducedthroughtheuseoflaboratory/invivoparadigmsinhumans–thus,welistedparadigmsthatinduceanalogsforthisaffectivestateaswellasstressfullifeeventsinterviewsthatprobepastexperiencesofloss.ItisimportanttohighlightthatthisissuedidnotapplytoourdiscussionofparadigmsthatassessAcuteThreat,PotentialThreat,andFrustrativeNonrewardbecausetherearewell-establishedparadigmsthatassesseachofthesethreeconstructs.
TherewasasecondimportantissuethatsignificantlyguidedtheNVSsubgroup’sdiscussion.Theoverallworkgroupwasinstructedspecificallytoidentifyonlyparadigmsforwhichtherewereclearbehavioraloutputs.Thus,forexample,paradigmsthatelicitedonlyaneuralresponseandnobehavioraloutput(e.g.,HaririHammerTask1)werenotincluded.Althoughthisparametermadesensegiventhebroaderaimsoftheworkgroup,andthefactthatfuturemeetingwouldfocusonadditionallevelsofanalysis,thishadtheeffectofnarrowingthetypesofparadigmsthatcouldbelisted.
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Finally,althoughtheNVSdomainsubgroupwasabletoprovideratingsformostofthe18criteriaforeachproposedparadigm,thegroupwasstruckbytheconsistentlylowratingsforseveralofthecriteria.Forexample,thefieldlacksnormativedataformanyoftheparadigms(criterion#8).Inaddition,whilethereareconventionsinthefieldforhowseveraloftheparadigmsshouldbeadministered(e.g.,numberoftrials,duration,etc.),mostoftheseparametershavenotbeenempiricallydeterminedorassessed(criterion#4).TheNVSsubgroupfeltthattheseareimportantareasforfutureresearch.
II.ORGANIZATIONOFTHEDOMAIN1. Concretesuggestionsforchangestoconstructs:additionsanddeletions.
Aswenotedabove,ourgroupdidnotspendagreatdealoftimediscussingthestructureandorganizationofdomains;however,wepresentbelowseveralspecificsuggestionsthataroseduringourmeeting.
(A)TheNVSandpositivevalencesystem(PVS)domainsarecloselyrelatedinthatbothrefertoresponsestomotivationallysalientstimuli,butofdifferentvalences.Paradigmsthatprovideopportunitiesforobservingbehavioralprofilesrelevanttoonedomainoftenhaveconditions(orversions)thatelicitevidenceofindividualdifferencesintheotherdomainaswell.IdentifyingareasofoverlapanddistinctionbetweentheNVSandPVSconstructs,bothconceptuallyintermsofpsychologicalprocessesandmethodologicallyintermsofbestpracticesforestablishingconvergentanddiscriminantvalidity,shouldbeapriorityforfuturework.
(B)Furtherconsiderationshouldbegiventoaddingthefollowingconstructstothenegativevalencedomain:1)emotionallability(andotheraspectsofthetimecourseofaffectiverespondingsuchasaffectivechronometry);2)pain,and;(3)affectivedecisionmaking.
2. Rationaleforrecommendedchanges.Thesuggestedconstructslistedabovearehighlyrelevantforseverementalillness,havewell-studiedneuralcircuits,andarenotrepresentedinotherdomainsoftheRDoC.
III.RECOMMENDEDTASKS1. Paradigms(SeeAppendixNVS-Iforratingsoftaskcriteriaforthefollowingparadigm
recommendations).
ACUTETHREAT:1)TrierSocialStressTestandsimilarsocialperformancetasks2,3;2)BehavioralApproachTest(e.g.,fear&disguststimuli);3)ColdPressor(andotherpaintolerancetasks)4-6;4)CO2Challenge7,8;5)StrangerTasks9,10;6)FearConditioningTasks(animportantcorrelateofAcuteThreat)11,12
POTENTIALTHREAT:NoShock,PredictableShock,UnpredictableShock(NPU-ThreatTask)13
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SUSTAINEDTHREAT:None
LOSS(analogofresponsetoloss):Sadness-elicitingfilmclips,butonlywithw/immersioninstructionsandfacialexpressionormoodratingsasdependentvariablesofinterest14,15
FRUSTRATIVENONREWARD:1)PointsSubtractionAggressionParadigm(PSAP)16,17;2)LaboratoryTemperamentAssessmentBatterytasksofBoxEmptyandTransparentBox18
2. Self-Report
ACUTETHREAT:manipulationcheckmeasures(e.g.,SUDS19,20),traitorexperiencemeasuresorfearedstimulusidentificationmeasures(e.g.,FearSurveySchedule21)
POTENTIALTHREAT-IntoleranceofUncertaintyScale(12itemversion22),BehavioralInhibitionScale(BIS)23,FearofNegativeEvaluationScale24,AnxietySensitivityIndex25,LifeEventsandDifficultiesSchedule(LEDS)26
SUSTAINEDTHREAT=YouthLifeStressInterview27,ChildhoodTraumaQuestionnaire28,LEDSdifficulties,TESI29,RiskyFamilies30,StressandAdversityInventory(STRAIN)31
LOSS=LEDS(socialexperienceoflossandpotentialthreat)26,STRAIN31
FRUSTRATIVENONREWARD=FrustrativeNonrewardResponsivenessSubscale32;QuestionnaireofDailyFrustrations33
IV.TASKSTHATREQUIREFURTHEREVALUATIONConstruct:AcuteThreat
Paradigm:IAPSpicturesorViewingofEmotionInducingFilms
Thisparadigmhasthepotentialtomeasureacutethreat,buttheNVSsubgroupfeltthatthiswouldonlybethecaseifthestimulussetwasrestrictedtoparticularlythreateningstimuliandnotsimplythosethataremorebroadly‘negative’invalence.Asanexample,trauma-specificstimuli(e.g.,helicopters,humvees)forveteranswithtrauma-relatedpsychopathologywouldbeanappropriateuseofthisparadigmtomeasureAcuteThreat.
Construct:SustainedThreat(moreaccurately,consequencesofexperiencingsustainedthreat)
Paradigm:Dot-ProbeTask(toassessvigilanceorattentionalcapture),ExogenousCuingTask(toassessinabilitytodisengagefromparticularclassesofstimuli),FacialMorphingTask(fordetectingthreatthresholds)
Asdiscussedabove,theconstructsmeasuredbythesetasksdonotdirectlymeasureindividuals’responsetoasustainedthreat,butrather,assessconstructsthatareconsequencesofhavingpreviouslyexperiencedsustainedthreat(atleastgiventhe
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definitionofSustainedThreatintheRDoCmatrix).TheNVSsubgrouphadanadditionalconcernwiththeDotProbetask.Despiteitswidespreaduse,severalstudieshaveraisedquestionsaboutitsreliability(e.g.,Staugaard,2009-PsychologicalScienceQuarterly,althoughseePriceetal.,2015-PsychologicalAssessmentforarecentreportinwhichadequatereliabilitywasobtainedusingnovelmethods).Thereare,however,multiplevariantsofthedot-probetask(e.g.,supraliminalpresentation,subliminalpresentation,verbalvs.pictorialstimuli,etc.),andthepsychometricpropertiesofthedifferentversionsofthedot-probearelikelytodiffer.Thedot-probetaskdid,however,achievehighratingsforseveraloftheothercriteria.ThisraisedanotherissueconcerningwhethercertaincriteriashouldbeweightedmoreheavilythanothersindeterminingwhetheraparadigmshouldberecommendedforaspecificRDoCconstruct.CriteriaratingsfortheDot-ProbeandExogenousCuingTasksareprovidedinAppendixNVS-II.
V.TASKSTHATARENOTRECOMMENDEDTheNVSsubgroupdecidedtofocusonexemplartasksforeachconstructratherthandiscussparadigmsthatareinuseandthenattempttofitthemtospecificRDoCconstruct.BelowarealistofparadigmsthatthegroupdiscussedbutthatwerejudgedtonotfitdirectlyintothedefinitionsofthefiveNVSRDoCconstructs,and/orthatmaybebetterrepresentedbyotherRDoCconstructs.
1. Explicit(butnotimplicit)emotionregulationparadigms-includinginstructionsofdistance,suppress,accept,maintain.Excludedbecausetheseparadigmsappeartoaddressregulation,whichisnotoneofthecurrentNegativeValenceRDOCconstructs.
2. Darknessinhumans/lightinrodents(excludedduetolittlebehavioralyieldasaparadigm)
3. FlankerTasktoAssessResponsetoErrors–Unclearwhetheritelicitsathreatresponse(asperthedefinitionsofthethreeRDoCthreatconstructs).Despiteclearlybeingnegativeinvalence,thisparadigmmayperhapsbelongwithmeasuresofcognitivecontrol.
4. Losslearning/lossaversion–Didnotfitwellwithacutethreatorbrain’sdefensivemotivationsystemmorebroadly.Perhapsismoreappropriatewithinthecognitivesystem.
5. QuestionnairesassessingSymptomDimensions(e.g.,guilt,shame,bereavement)ThesequestionnaireswereexcludedastheytapoutcomesoftheRDoCconstructsratherthaninductionsoftheRDoCconstructs
6. Autobiographicalmemoryprobes(formeasuringlossandthreat)–Theseparadigmscanelicitsensationsofloss,threat,etc.thatareidiographicinnature.However,theNVSsubgroupexcludedthemgiventhedifficultyofstandardizationforstrictlybehavioraloutcomemeasures.Theseparadigmsmaybeuseful,however,forelicitingbroadernegativeaffectivestates.
VI.REFERENCES1. HaririAR,TessitoreA,MattayVS,FeraF,WeinbergerDR.TheAmygdalaResponseto
EmotionalStimuli:AComparisonofFacesandScenes.NeuroImage.2002;17(1):317-323.
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AppendixNVS-I:NVSdomaingrouptableontaskcriteriaforrecommendedparadigms NVS
Construct
Task
ValidM
easureof
Construct(#1
)
Test-Retest
Reliability(#2)
Floo
r/Ce
iling(#
2)
PracticeEffects(#2
)
Longitu
dina
lStability
(#2)
Stan
dardize
dParameters(#4
)
Copyrig
ht(#
15)
Canitbe
usedacross
man
ysites?(#9)
Canitbe
usedwith
childrenorsp
ecial
popu
latio
ns?(#6)
Sensitivityto
w/in
pe
rson
cha
nge(#10
)
Tolerability(#18
)
Acutethreat TrierSocialStressTest
4 *3* *3* ? ? 2 5 5 Ages:5
Culture:4?
¾* 3
Acutethreat BehavioralapproachTest
4 ? ? N/A ? 2 5 5 Ages:5
Culture:4
5 4
Acutethreat Coldpressorandotherpaintolerancetasks
4 3 ? ? 3 4(butnotalwaysattendedtoinliterature)
5 3 Ages:5
Culture:5
3 3
Acutethreat CO2challenge 4 3 ? 4 5 5 Ages:5
Culture:4
4 3
Acutethreat Strangertasks 4 ? 5 1 3 2 5 5 Ages:5
Culture:5
1 3
Acutethreat(learning)
Fearconditioning
5 2 ? ? ? 4 5 5 Ages:5
Cultures:
5 4
Potentialthreat
NPUThreat-Task
4/5 4 5 ? ? 2 5 3 Ages:5
Culture:3
? 3
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Loss Sadnesselicitingfilmclips(seecaveatsabove)
4 ? ? ? ? 3 3(somemaybecopyrighted)
5 Ages:5
Culture:4
3 4
Frustrativenonreward
LabTAB:BoxEmpty,TransparentBox
5 4 5 ? 4(onlyifmult.tasksareused)
2 5 3 5,Adults(potentiallyadaptable)
Culture:?
1 4
Frustrativenonreward
PointsSubtractionAggressionParadigm(PSAP)
4 1* 1* ? 1? 1 5 3 1
Couldbeadapted
? 4
NVS
Con
struct(resto
fcrite
ria)
Task
(resto
fcriteria)
Alternateform
s(#2
)
Internalre
liability(#2)
Canbe
usedinclinical
trialsorsc
reen
ing(#5)
Stan
dalon
ebe
havioralta
sk?(#7)
Canusewith
imaging
orERP
?(#11
)
Relatb
twta
skperf&
ne
uralsigknow
n?
(#13
)
Clinicalphe
notype
(#14
)
Measureso
ne
constructo
rspe
cific
toone
?(#16)
Anytaskth
atcou
ldbe
mod
ified
?(#17
)
Norms(#8
)
Anim
alana
logue
(#12
)
Acutethreat TrierSocialStressTest
1 ?? 1 5 4* 2 5 4 -- 1 1
Threat Behavioralapproach
1 ? 4 5 5 5 5 5 Lotsofmodifications
1 5
Acutethreat ColdPressorandotherpaintolerancetasks
1 ? 2 5 5 5 4 1 Potentially 3 2
Acutethreat CO2challenge 1 N/A 4 5 5 4 5 5 Notreally 1 4
Acutethreat Strangertasks 1 4 2 5 2 2 2 3 ? 1 5
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Acutethreat(learning)
Fearconditioning
5 4 5 5 4 5 4 Many N/A 5
Potentialthreat
NPU 4 3(withSUDSratings)
3
5 5 5 5 -- 1 5
Loss Sadnesselicitingfilmclips,espw/immersion;facialexpormoodratings
4 ? 4 5 5 3 4 2/3 Yes,many 3 1
Frustrativenonreward
PointsSubtractionAggressionParadigm(PSAP)
1 ? 4 5 5 3 4 3(constructitselfisbroad.Measuretapslossaswellasthreat)
Couldbemodifiedforchildren
1 3
Frustrativenonreward
LabTAB:BoxEmpty,TransparentBox
1 4 3 5 2 -- 3 3(constructitselfisbroad.Measuretapscognitivecontrolandpositiveemotionality)
Couldbemodifiedforadults
1 2
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AppendixNVS-II:NVSdomaingrouptableontaskcriteriaforparadigmsthatneedmorework,ratedfrom1(noevidence)-5(strongevidence)
Construct
Task
ValidM
easureof
Construct(#1)
Test-Retest
Reliability(#2)
Floo
r/Ce
iling(#
2)
PracticeEffects
(#2)
Longitu
dinal
Stability(#
2)
Standardize
dParameters(#4)
Copyrig
ht(#
15)
Canitbe
used
acrossm
anysites?
(#9)
Canitbe
used
with
kidso
rspecial
popu
latio
ns?(#6)
w/in
person(#10)
Tolerability(#18)
VigilanceorAttentionalcapture
DotProbe(supraliminal1000mspresentationofangry/fearfulfaces)
3 2? 5 ? 2? 5 5 5 5 5 5
Inabilitytodisengagefromnegativestimulus
ExogenousCuingTask
3(psychometricsfornon-emotionalstimuliisavailable,butunclearifsimilarforemotionalstimuli)
5 ? 2 5 5 4 ? 5
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Construct(rest
ofcriteria)
Task
(resto
fcrite
ria)
Alternate
form
s(#2)
Internal
reliability(#2)
Canbe
usedin
clinicaltrials
orsc
reen
ing
(#5)
Standalon
ebe
havioral
task?(#7)
Canusewith
im
agingor
ERP?(#
11)
Relatb
twta
sk
perf&neu
ral
sigkno
wn?
(#13)
Clinical
phen
otype
(#14)
Measureso
ne
constructo
rspecificto
one?(#
16)
Anytaskth
at
couldbe
mod
ified
?(#17)
Norms(#8)
Anim
al
analogue
(#12)
VigilanceorAttentionalcapture
DotProbe(supraliminal1000mspresentationofangry/fearfulfaces)
2 1 4 5 5 4 5 3 -- 1 3
Inabilitytodisengagefromnegativestimulus
ExogenousCuingTask
2 ? 4 5 3 ? 3 3 Lotsofmodif.arepossible
1 1
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PositiveValenceSystemsFinalReport
MauricioR.Delgado,Ph.D.,PaulW.Glimcher,Ph.D.GregHajcak,Ph.D.,DiegoA.Pizzagalli,M.D.,Ph.D.(chair),MichaelT.Treadway,Ph.D.,BenjaminE.Yerys,Ph.D.
ExecutiveSummary
ThePositiveValenceSystems(PVS)DomainsubgroupcarefullyconsideredtheoriginalPVSconstructsanddiscussedover25tasksthatwererankedaccordingtopre-definedcriteria.DuringdeliberationsconcerningthePVSstructureandpossiblereconfigurations,particularemphasiswasplacedon(1)avoidingpotentialredundanciesacrossconstructs/sub-constructs,and(2)attemptingtoisolate“purer”constructs.Similarly,whenconsideringtasks,emphasiswasplacedonparadigmsthatisolategivensub-constructs.TheseconsiderationsledtoaproposedrestructuringofthePVSdomainintothreeconstructs(RewardResponsiveness,RewardLearning,RewardValuation),eachinvolvingthreesub-constructs.Amongalltasksdiscussed,16wereselectedforpotentialprioritization.Othertaskswerediscussedbutnotrecommended,whereasothersweredeemedpromisingbutrequiringmoreevaluation.
I.GeneralCommentsBeforediscussionsofthecurrentPVSstructureandpotentialtasks,theworkgroupdeliberatedonseveralgeneralpoints:
1. Manytasksthathavebeenadoptedwidelyintheliterature,particularlythosedevelopedforneuroimaging/neuropsychologicalstudiesinthelate1990s/early2000s,oftencannotdisentanglecurrentPVSconstructs/sub-constructs.ProminentexamplesaretheIowaGamblingTask1andtheMonetaryIncentiveDelay(MID)task2,whichareamongthemostwidelyusedtasksinthefield,andhaveprovidedawealthofvaluableinformation.Forexample,intheMIDtask,rewardvalueandrewardpredictionerror(RPE)areperfectlycorrelated,andthuscannotbede-conflated.
2. TheMIDtaskcurrentlyappearsinthematrixfortheconstructInitialResponsivenesstoReward,howeveroutcomesfromthistaskthatmeasureresponsetorewardcannotbedissociatedfromeachother.ThePVSgroupisnotrecommendingthistaskasameasureofInitialResponsivenesstoReward.Alternatively,theyarerecommendingitasameasureofRewardAnticipationbecausetheoutcomesassociatedwithanticipationareindependentandcanbeisolated.
3. Althoughworkgroupmembersdeemedregulatoryprocessesasbeingveryimportant,therewasconsensusthatregulationofPVSconstructswouldentailprocessesbettercapturedbytheCognitiveSystemsandArousalSystems.Accordingly,tasksprobingregulatoryprocesseswerenotdiscussed.
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4. Forsomesub-constructs(inparticular,“initialresponsivenesstoreward”),tasksyieldnodirectbehavioraloutput.However,theseconstructscanbemeaningfullyprobedwithimaging,electrophysiological,andperipheralpsychophysiologicaltechniques,andcouldbeaugmentedbyaffectiveratings.Giventhecentralityoftheseconstructsandtheirtranslationalvalueforpreclinicalmodels,theabsenceofdirectbehavioraloutputdidnotpreventtherecommendationofvarioustasks.Ingeneral,theabilityofatasktobeusedinconjunctionwithimaging,electrophysiologyorpsychophysiologywasdeemedaplus.
5. Someconstructs(e.g.,RewardPredictionError)requirecomputationalmodelingformeaningfulinterpretation.Accordingly,disseminationofsomeoftheproposedtaskswithinthissub-constructmightbecontingentupon(andthuslimitedby)expertiseincomputationalmodeling.
6. Althoughworkgroupmembersacknowledgedtheimportanceofself-reportmeasuresofPVSconstructs,performance-basedorbehavioraltaskswereprioritizedtomaximizepotentialtranslationtoandback-translationfrompreclinical(animal)models.
7. Whenevaluatingtasks,tolerability(i.e.,participants’experience)wasalsoconsidered.
II.OrganizationoftheDomain
DuringdeliberationsconcerningtheoriginalPVSconstructsandstructure,particularemphasiswasplacedon(1)avoidingpotentialredundanciesacrossconstructsandsub-constructs,and(2)attemptingtoisolate“purer”constructs.TheseconsiderationsledtoaproposedrestructuringofthePVSdomainintothreeconstructs(RewardResponsiveness,RewardLearning,RewardValuation),eachinvolvingthreesub-constructs(Table1).Rationalesforrestructuring/renamingaswellasde-prioritizationofsometasknominationsfromtheoriginalRDoCworkshopareprovidedinlatersectionsofthisreport.
TABLE1:ProposedRestructuringofthePVSdomain
Construct Sub-construct
1.RewardResponsiveness
1.1.InitialResponsetoReward
1.2.RewardAnticipation
1.3.RewardSatiation
2.RewardLearning
2.1.Habit
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2.2.ProbabilisticandReinforcementLearning
2.3.RewardPredictionError
3.RewardValuation
3.1.Reward(probability)
3.2.Delay
3.3.Effort
III.RecommendedTasks
Paradigmsthatwereevaluatedas“bestinclass”forgivenPVSsub-constructsaredescribedinmoredetailinAppendicesPVS-IIa-PVS-IIf.RatingsoneachsuggestedcriterionforthesetasksareprovidedinAppendixPVS-I.
1. RewardResponsivenessWeproposeRewardResponsivenessasaconstruct,whichincludesthreesub-constructs:initialresponsivenesstoreward,rewardanticipation,andrewardsatiation.
1.1. Initialresponsivenesstoreward:Thisisdefinedbyneuralandphysiologicalresponsetopositivereinforcers(money,positivepictures).Assuch,bydefinitiontherearenooptimalbehavioralmeasures,atleastnotincurrentinstantiations.
GuessingTask(e.g.,CardGuessingorDoors)3,4.Thesetaskshavenomeaningfulbehavioraloutput;rather,theyhavebeenwidelyusedinconjunctionwithe.g.fMRI,EEG/ERP,HR,GSRrecordings.Theycouldbemodifiedtoincluderatings.Thesetaskshaveexcellentconstructvalidityandpsychometricproperties,althoughmoreworkisneededtoevaluatetest-retestreliability.Therearegooddataonindividualdifferencesandsensitivitytochange.SeeAppendixPVS-IIafordetailedevaluations.
1.2. Rewardanticipation
MonetaryIncentiveDelayTask2.Probesrewardanticipation;modificationsareneededinordertoimproveitsabilitytoisolateanticipation;inparticularuseoflongerandjitteredinterstimulusintervals(e.g.,followinganexponentialfunctionwithover-representationofshorterinter-stimulusintervals)isexpectedtoimprovetheabilitytoisolateanticipation-relatedactivation.SeeAppendixPVS-IIbfordetailedevaluationsforeachcriterionforthistask.
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1.3. Sustainedresponsivenesstoreward:Wesuggestedrenaming“RewardSatiation”.
Fixed-RatioSatiationSchedule5.Excellentconstructvalidity,andpotentiallywouldhaveexcellentothercriteria,butneedssignificantdevelopment.Thisremainsarecommendationduetothelackofabetteroptionforthissubconstruct.
2. RewardLearningWeproposeRewardLearningasaconstruct,withsub-constructsofhabit,rewardpredictionerror,andprobabilisticandreinforcementlearning.
2.1. Habit
DevaluationTask6,7.Thistaskhasexcellentconstructvalidity.Therearesomeconcernsaboutabilitytorepeatedlyadminister(i.e.,practiceeffects)andtheuseofthetaskwithchildren/specialpopulations.Thereissomeevidenceforlinkstoclinicalfeatures.Thepsychometricpropertiesarenotyetknown,buttherearenobetteroptionsforrecommendation.SeeAppendixPVS-IIcfordetailedevaluationsforeachcriterionforthistask.
HabitTask(longertermreversallearning;8.Thistaskpotentiallyhasexcellentconstructvaliditybutinformationaboutotherparametersisunknown.
HabitLearningTask9.Thistaskhasexcellentconstructvaliditybutinformationaboutotherparametersisunkown.Thetaskmaynotbepracticalorefficientbecauseoflength.Someproposedmodificationsincludeadministeringthetaskinonlyonesessionsothatitcouldbecomemoresensitivetoindividualdifferences.
2.2. ProbabilisticandReinforcementLearning(formerRewardLearning)
ProbabilisticRewardTask10.Thistaskhasexcellentconstructvalidityandacceptabletest-retest,butthereisaneedtoevaluateinternalreliability(e.g.,computereliabilityforodd/eventrials).Itcanberepeated,andusedacrossmanyageandpopulations.Itissensitivetowithin-personchangeandhasknownrelationstoclinicalfeatures.Performanceonthistaskcanbemanipulatedbypharmacological(e.g.,dopaminergiccompounds)orbehavioral(e.g.,acutestressors)meansinpredictablemanners.Therearesomeemergingnormativedataforthistask.SeeAppendixPVS-IIdfordetailedevaluationsforeachcriterionforthistask.
PavlovianConditioning11.Inthesetasks,onestimuluspredictsapositiveoutcome.Inspiteofstrongconstructvalidity,thesetasksyieldpoorbehavioralprofiles.Thus,theyrequireimagingorpsychophysiological(e.g.,skinconductance,pupildilation)readouts.Suchtaskscouldbemodifiedinordertoincludeaffectiveratings.Thesetaskshaveunknownpsychometricproperties.Theycanberepeated,andusedacrossmanyageandpopulations.Thereisevidenceforsomelinkstoclinicalfeatures.Therearenonormativedataforthesetasks.
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ProbabilisticStimulusSelectionTask12.Thistaskhasexcellentconstructvalidity.Someconcernsaboutthistaskincludethefactthatmanyparticipantsdonotlearnit,itneedsworkfromotherlabsusingthetaskbesidestheinitiallab,anditwouldbedifficulttousewithchildrenorspecialpopulations.Thistaskcanberepeated.Thereissomeevidenceforlinkswithclinicalfeatures.Therearenonormativedataforthistask.
DriftingDoubleBandit13.Thistaskhasexcellentconstructvalidity,butunknownpsychometricsproperties.Thereislittleevidenceaboutlinkstoclinicalfeatures.Thesensitivityofthetasktowithin-personchangeorclinicalfeaturesisunknown.Thistaskcanberepeatedifdifferentstimulussetsaredeveloped,anditcanbeusedacrossmanyageandpopulations.Therearenonormativedataforthistask.
2.3. Expectancy/RewardPredictionError
RutledgePassiveLotteryTask14.Therearenobehavioraloutputsforthistask,butitisapuremeasureofRPE.Thepotentialdownsidetothistaskisthatmodelingthedatarequiresexpertiseincomputationalmodeling.
DriftingDoubleBandit13.Thistaskhasexcellentconstructvalidity,butunknownpsychometricsproperties.Thereislittleevidenceaboutlinkstoclinicalfeatures.Thesensitivityofthesetasktowithinpersonchangeorclinicalfeaturesisunknown.Thistaskcanberepeatedifdifferentstimulussetsaredeveloped,anditcanbeusedacrossmanyageandpopulations.Therearenonormativedataforthistask.
3. ValuationWeargueforaconstructcalledValuation,withsub-constructsofReward(whichwillencompassprobability),delay,andeffort.
3.1. Reward
ProbabilityChoiceTask15oranalogous—dropambiguity).SeeAppendixPVS-IIefordetailedevaluations.
Measuringthevaluesubjectsplaceonarewardinawaythatallowsinter-individualcomparisonbasedonlyonbehaviorisatheoreticallydifficultprospect.Usingonlybehavioronecanonlymeasuredifferenceinthe“rateatwhich”thesubjectivevalueofarewardgrowsasafunctionoftherateatwhichtheobjectivemagnitudeofagivenrewardgrows.Thisis,formally,thecurvatureoftheutilityfunctionfromeconomics.Typically,theutilityfunctionismeasuredbyaskingquestionsthatcompeteafixedsizedrewardagainstrewardsorgreatermagnitudebutlowerprobability.MeasurementsofthistypeareverywelldevelopedinpsychologyandbehavioraleconomicsandtypicallyarederivativeoftheclassicHoltandLaurie16approach.
WillingnesstoPay(BDM)17;seealso18
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Onewaytobegintocompareindividualresponsestorewardsistoasksubjectstopriceindollars(orinanothercurrency)themaximumamountthattheywouldbewillingtopaytoobtainaspecificgoodunderaspecificcondition.Twoissues,however,makethatmeasurementproblematic.First,asubjectwhoisactuallybiddingonarealgoodisoftenincentivizedtoreportalownumberinthehopesthattheywill‘game’theexperimenterintogivingthemthatgoodforless.Thisfirstconcernislargelyeliminatedinthe‘BDM’method.IntheBDMmethod,subjectsstatethemaximalpricethattheywouldbewillingtopayfromamenuofpossibleprices–say$1-$5in50centincrements.Oncetheyhavereportedthatpricetheydrawachipfromanurnwitheachchipbearingasinglepricefrom$1-$5in50centincrements.Ifthedrawnchipisbelowtheirpre-statedmaximumtheybuythegoodforthepriceonthechip,ifitisabovethepre-statedmaximumtheyarenotallowedtobuythegood.Underthisregimethesubjectsdobestiftheyreportthetruepricebecausethepricingmechanismisunaffectedbytheir‘bid’.BDMisforthisreasonthegoldstandardforassessingtrulyheld‘values’(indollars)fornon-monetarygoods.Thesecondproblemisthatsubjectsshouldneverbewillingtopaymorethanthemarketpriceforagoodiftheycanleavethelabimmediatelytopurchaseitforless.Typically,thisisdealtwithbyaskingthesubjectstoremaininthelabafterbiddingforsomefixedlengthoftime.Forraregoodsorgoodswithhighmarketpricesthisismuchlessofaproblem.
3.2. Delay
WorkgroupdeliberationsaswellasconsiderationofsuggestionsprovidedinresponsetotheRFIhighlightseveralcandidatetasks,whichhavecommonfeatures:Kable’stask19(mostoftenusedinclinicalsamples),TraditionalBickelHypothetical20(mostoftenusedinsubstanceabuseliterature),JohnsonandBickel21,GreenandMeyerson'shypothetical22(mostoftenusedinpsychologystudies).ThetaskbyKablewasdeemedoptimalforusewithneuroimagingduetoitsdisplaytechnique.
3.3. Effortvaluation/willingnesstowork.
EffortExpenditureforRewardTask23.Thistaskhasgoodconstructvalidity.Itcanbeusedinarangeofpopulations,issensitivetowithin-subjectmanipulationsandcanbeusedwithchildren(>9yearsold,althoughwithoutprobabilitymanipulation).Thetaskhasmoderatetoexcellenttest-retestreliability.Someminorconcernsaboutthistaskwereaboutaboutwhethereffortisconfoundedwithtimeontask,butitwasfeltthata“pure”versioncouldbedevelopedbyfixingtrialtimingstructure(sotimeontaskisheldconstant).SeeAppendixPVS-IIefordetailedevaluationsforeachcriterionforthistask.
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TABLE2:RecommendedTasksforeachPVSsub-constructConstruct/Sub-construct Task Keyreferences
1.RewardResponsiveness
1.1.InitialResponsetoReward
SimpleGuessingTask
(Delgadoetal.2000)2
(Carlsonetal.2011)3
1.2.RewardAnticipation MonetaryIncentiveDelayTask (Knutsonetal.2000)1
1.3.RewardSatiation Fixed-ratioSatiationSchedule (Sherman&Thomas1968)4
2.RewardLearning
2.1.Habit DevaluationTask (Gillanetal.2011)22
HabitTask (McKimetal.2016)7
HabitLearningTask (Tricomietal.2009)8
2.2.ProbabilisticandReinforcementLearning ProbabilisticRewardTask (Pizzagallietal.2005)9
PavlovianConditioning (O’Dohertyetal.2004)23
Driftingdoublebandit (Dawetal.2011)11
ProbabilisticStimulusSelectionTask (Franketal.2004)10
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2.3.RewardPredictionError RutledgePassiveLotteryTask (Rutledgeetal.2010)12
Driftingdoublebandit (Dawetal.2011)11
3.RewardValuation
3.1.Reward(probability) ProbabilityChoiceTask e(Levyetal.2010)13
WillingnessToPayTask (Beckeretal.1963)15
3.2.Delay
DelayedDiscountingTask
f(Kable&Glimcher2007)17
(Johnson&Bickel2002)19
(Green&Myerson2004)20
3.3.Effort EffortExpenditureforRewardTask (Treadwayetal.2009)21
eDropambiguitymanipulationfDeemedpreferableinconjunctionwithfunctionalneuroimaging
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IV.TasksthatrequiremoreevaluationRewardValuation
3.3.Effort
a)DeckChoiceEffortTask24 :Thiscognitiveeffort-baseddecisionmakingtaskwasdevelopedforuseinclinicalpopulations24.TheDecktaskinvolvesmakingchoicesbetweenhardvs.easycognitivetasks(i.e.,cognitivesetswitching)fordifferentlevelsofmonetaryreward.Itisbasedonacognitiveefforttaskoriginallydevelopedforhealthyindividuals25.Theconstructofcognitiveefforthasbeenstudiedinanimalmodels26;thistaskwasnominatedinresponsetoNIMHRFIpostedonMonday3/28/2016(https://grants.nih.gov/grants/guide/notice-files/NOT-MH-16-007.html).
• Evidenceforconstructvalidityintermsofthemechanismthetestisthoughttoassess:Evidenceforconstructvaliditystemsfrom:itsabilitytodistinguishschizophreniapatientsfromhealthysubjects,relationstoothereffort-baseddecisionmakingtasksinschizophrenia,non-clinicalresearchshowingsomeconvergentvalidityfordifferenttypesofcognitiveefforttasks,andneuroimagingstudies.
• Evidenceforreliability,ofanyform,includinginternalconsistency,test-retestreliability,etc.:Modest-to-Good(ICC=.67)one-monthtest-retestreliabilityinpatientswithschizophreniar24.
• Evidenceforotherrelevantpsychometriccharacteristicsaboutthetest,includingpracticeeffects,floororceilingeffects,etc.:Thetaskperformedreasonablywellregardingfloor,ceiling,orpracticeeffectsinschizophrenia24.
• Descriptionsofanyknownanimalhomologuesforthistest:Cognitiveeffort-baseddecisionmakingtaskshavebeenusedinanimalmodels26.
• Evidenceoftaskimprovementwithpsychologicalorpharmacologicaltreatment:None
b)CognitiveEffortDiscounting(COGED)task27:TheCOGEDisusedtoassessevaluationofcognitiveeffortcosts,balancedagainstrewards.Theextenttowhichanindividualdiscountsareward,contingentonperformanceofademandingtask,isthoughttoindicatehowstronglytheyexperienceeffortcostsinthecognitivedomain,andconversely,theirmotivationforgoalpursuitviacognitiveengagement.
• Evidenceforconstructvalidityintermsofthemechanismthetestisthoughttoassess:COGEDissensitivetobothstateandtraitfactorsthatsupportitsconstructvalidity.Statefactorsincludeworkingmemoryload(‘N’ontheN-backtask),whichincreasesdiscountingandofferamount,whichdecreasesdiscounting27.TraitfactorsincludeNeedforCognitionandcognitiveaging27andnegativesymptomsinschizophrenia28.Moreover,unpublishedobservationsindicatethatCOGEDisstronglycorrelatedwithswitchcostsinatasks-switchingparadigm(steepdiscountersontheN-backhavelargerswitchcostsinadifferenttask-switchingparadigm),andaweakercorrelationwithdelaydiscounting(steepeffortdiscountersarealmostinvariablysteep/impatientdelaydiscounters).Thislatterobservationdovetailswithrecentstudiesofcognitiveeffectsindelaydiscounting
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supportingthatpatientchoicebehaviorrequires(potentiallyeffortful)workingmemoryallocationduringdecision-making.Finally,ataneurallevel,recentobservations(inpreparationforpublication)includethatdimensionsofrewardamountandtaskloadarebothrobustlyencodedincanonicalsubjectivevalueencodingregionslikethevmPFCandposteriorcingulatecortex,asparticipantsevaluatecognitiveeffort-contingentrewards.Also,whileparticipantsareengagedwiththeN-backtask,steepereffortdiscountersshowgreaterrecruitmentinanumberoftask-positiveregionsincludingthefronto-parietal,salience,anddorsalattentionnetworks.
• Evidenceforreliability,ofanyform,includinginternalconsistency,test-retestreliability,etc.:Limitedevidence,butincludestheaforementionedinter-individualcorrelationsbetweenCOGEDandNeedforCognitionandnegativesymptoms.Correlationswiththesetraitdimensionssupportreliability.Inasmallsample(N=25participants),theICCoftheAreaUndertheDiscountingCurvemeasureofCOGED,acrossthreesessionsamonghealthyyoungadults,was0.47with95%CIof[0.23,0.69].TotheextentthatCOGEDcapturesbothtraitandstateeffects(e.g.fatigueorsleepdeprivation29,somevariabilityisexpected.
• Evidenceforotherrelevantpsychometriccharacteristicsaboutthetest,includingpracticeeffects,floororceilingeffects,etc.:Dependingonparadigmdesign,briefexposuretotheN-backtaskpriortodiscountingyieldsshallowerdiscountingthanprolongedexposurewhich,atthelimit,producesnodiscounting(individualsalwaysselectthemoredemandingoptionformoremoney),restrictinginter-individualvariability.
• Descriptionsofanyknownanimalhomologuesforthistest:ThenearestistheRatCognitiveEffortTask(RCET)ofCockerandcolleagues30.Therearemanyotherphysicaleffortparadigms(e.g.T-mazesforrats,orlevelpullsformonkeys),butthisistheonlyanimalcognitiveefforttask.
• Evidenceoftaskimprovementwithpsychologicalorpharmacologicaltreatment:Noneisavailabletodate.
c)AdditionalEffort-basedTasks
Thefollowingtasksweredeemedaspromisinginlightoftheirpotentialabilitytoprobeparticularsub-constructsbutrequiremoreworkandevaluation(oftenbecausetheyhavebeeninvestigatedinalimitednumberofstudies):
• PhysicalEffort:GripForceTask31,32• PhysicalEffort:BeautifulFacesTask33andrelatedtasks(e.g.,toproberestrictedinterestin
autism34):Tasksthatrequireefforttoexperienceareinforcer(e.g.,beautifulfaces)needtoberefinedtobetterindexeffort.
V.Tasksthatarenotrecommended1.RewardResponsiveness
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1.1.InitialResponsetoReward
MonetaryIncentiveDelayTask2:TheMIDwasrecommendedforthesub-construct“RewardAnticipation”(seeSectionIII,Point1.2.)butnotforthesub-construct“InitialResponsivenesstoReward”duetopoorvalidityindissociatingpredictionerrorandoutcomevaluesignals.Specifically,formalmodelingexpectationofrewardoutcomeinthistaskischallenging,asitwillbeinfluencedbybothoutcomesofpriortrialsaswellasperformanceonthecurrenttrial(e.g.,dependingonRTtothetarget,participantshaveagoodexpectationoftheupcomingoutcome).Moreover,commonattemptstoworkaroundthislimitationbymodelingexpectationasjusttheaveragerewardrateresultinpredictionerrorvaluesthatareco-linearwithoutcomevalues.
CueReactivityTasks:Notconsideredbecausethesetaskslikelyengagerewardanticipationinsomeconditions,butinitialresponsivenesstorewardinothers.
1.2.RewardAnticipation
None.
1.3.RewardSatiation
DevaluationTasks:Poorconstructvalidityforthissub-construct—likelyamuchbettermeasureofhabit.
2.RewardLearning
2.1.Habit
KnotTyingandSerialResponseTasks:notdiscussedbecausetheymostlyprobeprocedurallearning;similarly,AttentionalBlindnessTaskswerenotconsideredbecausetheyassessattentionalbiasrelatedtoexpertise.
2.2.ProbabilisticandReinforcementLearning
DriftingBandit14:Excellentproperties;ithasbeenusedinstudiesinParkinsonanddopaminergicchallenges;itcanmeasureexploration/exploitationandallowstofitlearningrateandbias.Itwasnotdiscussedfurther,however,becauseDoubleBanditTasks(e.g.,Dawetal.2011)yieldthesameoutcomevariablesandallowonetoparsebothmodel-basedandmodel-freeparametersinthesametask,andarethusmoreefficient.
PavlovianInstrumentalTransferTasks35:interestingtaskbutitrequiresworkbeforewidedisseminationbecause~30%ofparticipantsareunabletolearnit).
2.3.RewardPredictionError
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None.
3.RewardValuation
3.1.Reward(probability)
None.
3.2.Delay
None.
3.3.Effort
ProgressiveRatioTask36:Inspiteoftheirwidespreaduseintheliterature,ProgressiveRatioTaskswerenotconsideredbecausetheyconfoundeffort,timediscounting,rewardmagnitude(andsatiety).
VI.References1. BecharaA,DamasioH,TranelD,DamasioAR.DecidingAdvantageouslyBeforeKnowing
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Appendix1:Ratingsoftasksrecommendedforconsideration.
DOMAIN:POSITIVEVALENCESYSTEMS
Criteria(Rateeachonascaleof1-5,with1=doesnotdoagoodjobofmeetingthecriterion;5=doesanexcellentjobmeetingthecriterion
Construct Task
ValidM
easureof
Construct
Test-Retest
Reliability
Floo
r/Ce
iling
PracticeEffects
Longitud
inal
Stab
ility
Sensitivetow/in
person
cha
nge
Stan
dardized
Parameters
Canitbeused
acrosssites?
Canitbeused
with
kidsorspecial
popu
lation
s?
Arenormativeda
ta
available?
Arerelationsto
clinicalfe
atures
know
n?
Notcop
yrighted
?
1.RewardResponsiveness
1.1.InitialResponsetoReward
SimpleGuessingTask(e.g.50%CardTask)
57 3 5 5 4 5 3 5 48 1 4 5
7Butnobehavioraloutcomeavailable.Itwouldrequiretheadditionofself-reportorpsychophysiologicalassessments.8Withchildrenthan7yearsold
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1.2.RewardAnticipation
MonetaryIncentiveDelayTask 19,210
211 5 4 1(u)12
5 3 5 5 5 4 5
1.3RewardSatiation
Fixed-ratioSatiationSchedule 5 1 4 5 1 1 1 4 4 1 1 5
2.RewardLearning
2.1.Habit DevaluationTask
HabitTask
HabitLearningTask
5 1(u)f 4 3 1(u)f 1(u)f 1 4 313 1 1 5
2.2.ProbabilisticandReinforcementLearning
a)ProbabilisticRewardTask
b)PavlovianConditioning
c)Driftingdoublebandit
d)ProbabilisticStimulusSelectionTask
5
5a
5
5
3
1(u)f
1(u)f
1(u)f
5
4
5
3
5
3
5
5
4
1(u)f
1(u)f
1(u)f
5
3
2
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4
3
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3
4b
5
4
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1
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1
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4
414
5
5
5
2.3.RewardPredictionError
a)RutledgePassiveLotteryTask
b)DriftingDoubleBandit(seeabove)
5
5
1(u)f1(u)f
3
5
4
5
1(u)f1(u)f
1(u)f
2
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4
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9Forbehavioraloutcome10Forneuraloutcome11GoodbutlowN12Unknown13Children,OCD,autism14Freelyavailableforresearchers/non-profits;usebyindustryrequireslicensing
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3.RewardValuation
3.1.Reward(probability)
ProbabilityChoiceTask
WillingnessToPayTask
5
5
1(u)f1(u)f
3
3
4
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1(u)f1(u)f
1(u)f
1(u)f
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3.2.Delay DelayedDiscountingTask
3.3.Effort EffortExpenditureforRewardTask 415 3 5 4 4 5 3 5 4 2 4 4h
15Itmanipulateseffortsandtimelineatthesametime,thusnotapuremeasureofeffort.Modificationscouldbeapplied.
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AppendixPVS-IIa:DetailedEvaluationCriteriaforSimpleGuessingTask
PVSConstruct:RewardResponsiveness
PVSSub-construct:InitialResponsetoReward
A)Card-GuessingTask(e.g.,Delgadoetal.)
1. Howvalidatestoftheconstructisthetask?
Thecardguessingtaskwasdevelopedtoidentifyneuralcircuitsinvolvedinrewardprocessing.Morespecifically,thetaskallowsforthecomparisonofbrainresponsestopositiveoutcomes(e.g.,receivingamonetaryreward)comparedtoneutralornegativeoutcomes(e.g.,monetaryloss).Theoriginalversionofthetask[1]doesnotrequirelearningormuchpracticeandmerelyinvolves“guessing”decisionswhetherthenumberofacardishigherorlowerthan5(ata50%probability),withguessesresultinginpositive(acorrectresponse),neutralornegative(anincorrectresponse)outcomes,thuscontrollingforchangesinresponsestorewardasafunctionoflearningorexpectations.Priorstudieshaveshownthat:(1) Acrossseveralparadigms,acomparisonofpositiveandnegativeoutcomesyields
activationinreward-relatedregions,primarilydorsalandventralstriatum(forreviewsee[2]).Thiscanbeobservedinbothevent-relatedandblockeddesigns.
(2) Thisreward-relatedresponseiscontext-dependentandcanbemodulatedbyfactorssuchasmagnitude[3],probability[4]andthetypeofrewardutilized,fromnon-monetarypositivefeedback[5,6]tosymbolicstimulirepresentingfood[7].
(3) Thisreward-relatedresponseisbluntedbyexposuretoacutestress[8]ordeprivationofnicotine[9].
(4) Thisreward-relatedresponsecharacterizedbythecard-guessingtaskhasbeenfoundtobealteredinapopulationofpatientsrecoveredfromanorexianervosa[10]andbulimianervosa[11]aswellasadolescentswithAnorexiaNervosa[12].
(5) Thisreward-relatedresponsecharacterizedbythecard-guessingtaskhasalsobeenfoundtobealteredinapopulationofadolescentswithmajordepressivedisorder[13,14],withsuchalterationsbeingpredictiveofdepressivesymptomsinpubertaladolescents[15]orrelatedtochallengingsocialexperiencesinearlyadolescence(suchaspeervictimization;[16]).
(6) Reward-relatedresponsescharacterizedbythecard-guessingtaskaresusceptibletothesocialcontextinwhichtheyarereceived,beingalteredbasedontheperception
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ofacooperativeorcompetitivescenario[17,18]orasafunctionofwhethertheinteractioniswithapersonorcomputer[19,20].
(7) Childhoodmeasuresofstress[21]andemotionalneglect[22]correlatewithblunted-rewardsensitivityasmeasuredbyneuralresponsestorewardingoutcomesinthecard-guessingtask.
(8) Themagnitudeofthisreward-relatedresponsecorrelateswithpreferencesforimmediateoverdelayedrewards[23]andriskychoicesinsomecontexts[19],aswellasanunwillingnesstoresistcigarettesmoking[24].
(9) Sustainedactivityinreward-relatedregionsduringthisparadigminthelaboratorycorrelateswithrealworldpositiveemotionalresponsesincontrolparticipants[25]andpositiveaffectinadolescentmajordepressivedisorder[14].
(10) Thecard-guessingtaskcanyieldresultsinlong[1]orshort(localizer;[26])versionsandcanbemodifiedtoalsolookatanticipationofrewardorchangesasafunctionoflearningorotherfactors(e.g.,socialcontext[18]).
2. Doesthetaskhavegoodpsychometriccharacteristics(incl.highinternalreliability,test-
retestreliability,sensitivity/specificity,limitedpracticeeffects,availabilityofalternate
forms,longitudinalstability)?
i. highinternalreliability:Notevaluatedii. test-retestreliability:Notevaluatediii. Sensitivity/specificity:Notevaluatediv. Limitedpracticeeffects:Inoriginalversion,therearenoknownpracticeeffects.v. Availabilityofalternateforms:Yes,thereisahighdegreeofflexibilitywiththis
paradigmandithasbeenadaptedfordifferentquestions,ortimingconstraintsorforspecificpopulations.
vi. Longitudinalstability:Notevaluated
3. Areparametersforadministeringthetask(e.g.,numberoftrials,stimuluscharacteristics,
etc.)standardizedonanempiricalbasis?
i. Therearenoformalempiricalparametersasbehavioralmeasuresbeyondreactiontimeandsubjectivemeasuresthatserveasmanipulationchecksarenotincludedoroptimalforanalysis.Therearepublishedminimumamountoftrialsinvariousadaptationsthathavebeeneffective.
4. Isthetaskfreefromfloor/ceilingeffectswhichwouldprecludeuseinsubjectswitha
rangeofimpairment?
i. Yes
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5. Doesthetaskhavethesameperformancecharacteristicsacrosscultures?Isitfreefrom
culture-andlanguage-specificfeatures/stimuli?
i. Thetaskshouldbefreefromcultureandlanguage-specificfeaturesbeyondchangingthecurrency.
ii. Oneexample:thetaskhasbeenruninGermanywithadultADHDparticipantstosimilarresults(Wilbertzetal.,2012).
6. Isthetasksensitivetochangeandlackandlossoffunction?
i. Yes,asevidencedfromitsuseindiversepatientpopulationspreviouslydescribed.
7. Canthetask(oritsanalog)beusedinanimals?
i. Yes,althoughtherearenoclearparalleltasksatthistime.
8. Canthetaskbeusedacrossagegroups?
i. Yes,thetaskhasbeenusedwithchildren,adolescentsandolderadults.
9. Canthetaskbeusedwithmethodstointerrogatebraincircuitry(e.g.,fMRI,EEG,etc.)?
i. Theprimarygoalofthistaskistoobservereward-relatedactivation.Assuch,itisusedprimarilywithneuroimagingmethodssuchasfMRI.
10. Isthereconsensusonwhichmetric/scoreshouldbeconsideredtobeprimary?
i. Thetaskservesprimarilyasameasureofneuralactivityofrewardresponses.Thus,theprimarymeasureisameasureofBOLDsignalsinreward-relatedregions.
11. Areadequatenormativedataavailableacrossage,gender,education,ethnicity,SES?
i. Thedataareavailableacrossmultipleparadigmsbuthavenotbeenaggregated.
12. Aretherelationshipsbetweentaskperformanceandneuralsignal(s)known?
i. Yes(sepoint#1)
13. Aretherelationshipsbetweentaskperformanceandclinicalfeature(s)known?
i. Yesforsomeclinicalfeatures(seepoint#1)
14. Isthetaskfeasibleforadministrationacrosssites?
i. Yes
15. Canthetaskbeusedasastand-alonebehavioraltask?i. No
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16. Whatworkisneededtogetthistaskreadyforuseinclinicaltrials?
i. Selectionofoneversionoftheparadigmthatcanbestandardized(e.g.,basedonamountoftrialsandoptimaltiming).
17. Isthetaskcopyrighted?i. No
References
1. Delgado,M.R.,etal.,Trackingthehemodynamicresponsestorewardandpunishmentin
thestriatum.JNeurophysiol,2000.84(6):p.3072-7.2. Delgado,M.R.,Reward-relatedresponsesinthehumanstriatum.AnnNYAcadSci,
2007.1104:p.70-88.3. Delgado,M.R.,etal.,Dorsalstriatumresponsestorewardandpunishment:effectsof
valenceandmagnitudemanipulations.CognAffectBehavNeurosci,2003.3(1):p.27-38.4. Delgado,M.R.,etal.,AnfMRIstudyofreward-relatedprobabilitylearning.Neuroimage,
2005.24(3):p.862-73.5. Delgado,M.R.,V.A.Stenger,andJ.A.Fiez,Motivation-dependentresponsesinthe
humancaudatenucleus.CerebCortex,2004.14(9):p.1022-30.6. Tricomi,E.,etal.,Performancefeedbackdrivescaudateactivationinaphonological
learningtask.JCognNeurosci,2006.18(6):p.1029-43.7. Luking,K.R.andD.M.Barch,Candyandthebrain:neuralresponsetocandygainsand
losses.CognAffectBehavNeurosci,2013.13(3):p.437-51.8. Porcelli,A.J.,A.H.Lewis,andM.R.Delgado,Acutestressinfluencesneuralcircuitsof
rewardprocessing.FrontNeurosci,2012.6:p.157.9. Wilson,S.J.,etal.,Effectofsmokingopportunityonresponsestomonetarygainandloss
inthecaudatenucleus.JAbnormPsychol,2008.117(2):p.428-34.10. Wagner,A.,etal.,Alteredrewardprocessinginwomenrecoveredfromanorexia
nervosa.AmJPsychiatry,2007.164(12):p.1842-9.11. Wagner,A.,etal.,Alteredstriatalresponsetorewardinbulimianervosaafterrecovery.
IntJEatDisord,2010.43(4):p.289-94.12. Bischoff-Grethe,A.,etal.,Alteredbrainresponsetorewardandpunishmentin
adolescentswithAnorexianervosa.PsychiatryRes,2013.214(3):p.331-40.13. Forbes,E.E.,fMRIstudiesofrewardprocessinginadolescentdepression.
Neuropsychopharmacology,2011.36(1):p.372-3.14. Forbes,E.E.,etal.,Alteredstriatalactivationpredictingreal-worldpositiveaffectin
adolescentmajordepressivedisorder.AmJPsychiatry,2009.166(1):p.64-73.15. Morgan,J.K.,etal.,Neuralresponsetorewardasapredictorofincreasesindepressive
symptomsinadolescence.NeurobiolDis,2013.52:p.66-74.
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16. Casement,M.D.,etal.,Girls'challengingsocialexperiencesinearlyadolescencepredictneuralresponsetorewardsanddepressivesymptoms.DevCognNeurosci,2014.8:p.18-27.
17. Fareri,D.S.andM.R.Delgado,Differentialrewardresponsesduringcompetitionagainst
in-andout-of-networkothers.SocCognAffectNeurosci,2014.9(4):p.412-20.18. Fareri,D.S.,etal.,Socialnetworkmodulationofreward-relatedsignals.JNeurosci,2012.
32(26):p.9045-52.19. Delgado,M.R.,etal.,Understandingoverbidding:usingtheneuralcircuitryofrewardto
designeconomicauctions.Science,2008.321(5897):p.1849-52.20. Fareri,D.S.,L.J.Chang,andM.R.Delgado,Computationalsubstratesofsocialvaluein
interpersonalcollaboration.JNeurosci,2015.35(21):p.8170-80.21. Hanson,J.L.,etal.,Cumulativestressinchildhoodisassociatedwithbluntedreward-
relatedbrainactivityinadulthood.SocCognAffectNeurosci,2016.11(3):p.405-12.22. Hanson,J.L.,A.R.Hariri,andD.E.Williamson,BluntedVentralStriatumDevelopmentin
AdolescenceReflectsEmotionalNeglectandPredictsDepressiveSymptoms.BiolPsychiatry,2015.78(9):p.598-605.
23. Hariri,A.R.,etal.,Preferenceforimmediateoverdelayedrewardsisassociatedwith
magnitudeofventralstriatalactivity.JNeurosci,2006.26(51):p.13213-7.24. Wilson,S.J.,etal.,Weakventralstriatalresponsestomonetaryoutcomespredictan
unwillingnesstoresistcigarettesmoking.CognAffectBehavNeurosci,2014.14(4):p.1196-207.
25. Heller,A.S.,etal.,TheNeurodynamicsofAffectintheLaboratoryPredictsPersistenceof
Real-WorldEmotionalResponses.JNeurosci,2015.35(29):p.10503-9.26. Speer,M.E.,J.P.Bhanji,andM.R.Delgado,Savoringthepast:positivememoriesevoke
valuerepresentationsinthestriatum.Neuron,2014.84(4):p.847-56.
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B.DoorsTask(e.g.,Hajcaketal.)
1. Howvalidatestoftheconstructisthetask?
TheDoorsTaskissimplegamblingtaskthatisintendedtoelicitphysiologicalresponsestoreceivingrewardandloss.Oneachtrial,participantsviewtwodoorsandaretoldthatonedoorleadstomonetaryrewardandoneleadtomonetaryloss;participantsselectadoorbyclickingtheleftorrightmousebutton,andsubsequentlyreceivefeedbackindicatingeitherawin($.50)oraloss($.25).Thetaskincludes60trials,andfeedbackisexactlyequiprobable(i.e.,30gainsand30losses,presentedinarandomorder).
Thistask,andfunctionallyidenticalvariantsliketheballoontaskorcardsguessingtask,wasdesignedtoexaminephysiologicalresponses(i.e.,EEG,fMRI)tofavorable(i.e.,winningmoney)versusunfavorable(i.e.,losingmoney)feedback.ThestudiesbelowfocusonERPresponsetorewardandstriatalresponsetoreward—thoughotherregionsofinteresthavebeenexaminedinrelationtoindividualdifferences.Priorstudieshaveshownthatneuralresponsetorewardis:
(1) RelatedacrossbothERPandfMRImethods1,5,11.(2) Relatedtobehavioralmeasuresofrewardsensitivityandself-reportedsensitivityto
reward2.andreal-worldpositiveaffectiveexperience8.(3)Bluntedinrelationtoincreaseddepressivesymptomsinbothchildrenandadults2,4,9.
(4)BluntedamongindividualswithMDD,especiallyinrelationtoanhedonicsymptoms7,9,14.OnerecentstudyfoundreducedrewardresponseamongremittedmelancholicMDDindividuals20.
(5)Reducedamongindividualsathighriskfordepression12,21,andreducedreward-relatedbrainactivitypredictsincreasesindepressivesymptoms2,4,16andnew-onsetdepressionprospectively2,16.
(6)Abnormalamongindividualswithaddiction17,especiallyinrelationtoanhedonicsymptomsandpredictedrewards.
(7)IslinkedtogenesthatregulateDA10.(7)Correlatedamongfirst-degreerelatives(r=0.31)21.(8)Thatisbluntedindepressionmayimprovewiththerapy6.
2. Doesthetaskhavegoodpsychometriccharacteristics(incl.highinternalreliability,test-
retestreliability,sensitivity/specificity,limitedpracticeeffects,availabilityofalternate
forms,longitudinalstability)?
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i. highinternalreliability:highinternalreliabilityforbothstriatumresponsetoreward(r=0.66)15andERPresponsetoreward(r=0.8515;r=0.903;r=0.8913).
ii. test-retestreliability:usingfMRI–moderate(ICCs=0.55–0.62)18;usingERP,moderate-to-high(r=0.673;r=0.7113)
iii. Sensitivity/specificity:ROCanalysesnotperformedyet(butdataareavailable)iv. Limitedpracticeeffects:taskcanbedonemanytimes.v. Availabilityofalternateforms:Yes,doorstaskisfunctionallyidenticaltocardguessing
andsimilartaskswhereprobabilityofrewardis50%oneachtrial7,8.
3. Areparametersforadministeringthetask(e.g.,numberoftrials,stimuluscharacteristics,
etc.)standardizedonanempiricalbasis?
i. Taskstimuliwereoptimizedtobesimpleandcanbeusedwithalargeagerange(aslowas4yearsinongoingwork);althoughthetaskproducesinternallyreliablereward-relatedneuralmeasureswith40-60trials,itappearsthathalfasmanytrialsmayberequired15—thoughwhethertasklengthimpactsrelationshipswithindividualdifferencesisunknown.
4. Isthetaskfreefromfloor/ceilingeffectswhichwouldprecludeuseinsubjectswitha
rangeofimpairment?
i. Yes;taskhasbeenusedwithchildrenandotherspecialpopulations.
5. Doesthetaskhavethesameperformancecharacteristicsacrosscultures?Isitfreefrom
culture-andlanguage-specificfeatures/stimuli?
i. InadditiontotheU.S.,thetaskhasbeenusedinAsiansamples,wherereward-relatedneuralactivityhasalsobeenrelatedtodepressionandanhedonia14.
ii. Thereisnoapriorireasontobelievethatitwouldperforminaculturally-specificway.
6. Isthetasksensitivetochangeandlackandlossoffunction?
i. Yes,asevidencedbyfindingsinpatientsamples(seeabove).
7. Canthetask(oritsanalog)beusedinanimals?
i. Intheory,yes;thoughananimalversionhasnotbeencreated.
8. Canthetaskbeusedacrossagegroups?
i. Yes,publisheddatain9year-olds12;ongoingworkin3-6yearolds.
9. Canthetaskbeusedwithmethodstointerrogatebraincircuitry(e.g.,fMRI,EEG,etc.)?
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i. Yes;thetaskhasbeenusedtoexaminereward-relatedbrainactivityusingbothEEGandfMRI.
10. Isthereconsensusonwhichmetric/scoreshouldbeconsideredtobeprimary?
i. RewardPositivity(inERP),orthedifferencebetweenrewardandnon-reward(i.e.,averageactivityfrom250-350msfollowingfeedbackatFCz;thisappearslateramongyoungersubjects)
ii. Reward-circuitactivationusingfMRI(i.e.,striatalresponse,medialprefrontalcortexresponse)
11. Areadequatenormativedataavailableacrossage,gender,education,ethnicity,SES?
i. Thetaskhasbeenadministeredtomorethan1,000individuals.Age-andgender-relatednormsarenotavailable,butcouldbecreated.
12. Aretherelationshipsbetweentaskperformanceandneuralsignal(s)known?
i. Thetaskassessesinitialresponsivenesstoreward,operationalizedintermsofneuralresponse.Behaviorally,itispossibletoexaminewin-stay/lose-shiftstrategies,thoughthesedatahaverelatedinconsistentlytoneuralresponsetorewards.
13. Aretherelationshipsbetweentaskperformanceandclinicalfeature(s)known?
i. Neuralresponsetorewardonthedoorstaskhasbeenrelatedtodepressionandrelatedconstructs—bothcross-sectionallyandprospectively.
14. Isthetaskfeasibleforadministrationacrosssites?
i. Yes;itiscurrentlybeingusedatmanyresearchsites.
15. Canthetaskbeusedasastand-alonebehavioraltask?i. No
16. Whatworkisneededtogetthistaskreadyforuseinclinicaltrials?
i. Examineimpactofpharmacologicalchallengeii. Animalmodeloftaskiii. Examinewhethermeasuresaresensitivetotreatmentresponse
17. Isthetaskcopyrighted?
i. No.
References
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1. Becker,M.P.,Nitsch,A.M.,Miltner,W.H.,&Straube,T.(2014).Asingle-trialestimationofthefeedback-relatednegativityanditsrelationtoBOLDresponsesinatime-estimationtask.TheJournalofNeuroscience,34(8),3005-3012.
2. Bress,J.N.,&Hajcak,G.(2013).Self-reportandbehavioralmeasuresofrewardsensitivitypredictthefeedbacknegativity.Psychophysiology,50(7),610–616.
3. Bress,J.N.,Meyer,A.,&Proudfit,G.H.(2015).Thestabilityofthefeedbacknegativityanditsrelationshipwithdepressionduringchildhoodandadolescence.Development
andPsychopathology,27(4pt1),1285–12944. Bress,J.N.,Smith,E.,Foti,D.,Klein,D.N.,&Hajcak,G.(2012).Neuralresponseto
rewardanddepressivesymptomsinlatechildhoodtoearlyadolescence.BiologicalPsychology,89(1),156–162.
5. Carlson,J.M.,Foti,D.,Mujica-Parodi,L.R.,Harmon-Jones,E.,&Hajcak,G.(2011).VentralstriatalandmedialprefrontalBOLDactivationiscorrelatedwithreward-relatedelectrocorticalactivity:acombinedERPandfMRIstudy.Neuroimage,57(4),1608-1616.
6. Dichter,G.S.,Felder,J.N.,Petty,C.,Bizzell,J.,Ernst,M.,&Smoski,M.J.(2009).TheEffectsofPsychotherapyonNeuralResponsestoRewardsinMajorDepression.BiologicalPsychiatry,66(9),886–897.
7. Forbes,E.E.,Hariri,A.R.,Martin,S.L.,Silk,J.S.,Moyles,D.L.,Fisher,P.M.,…Dahl,R.E.(2009).AlteredStriatalActivationPredictingReal-WorldPositiveAffectinAdolescentMajorDepressiveDisorder.AmericanJournalofPsychiatry,166(1),64–73.
8. Forbes,E.E.,Ryan,N.D.,Phillips,M.L.,Manuck,S.B.,Worthman,C.M.,Moyles,D.L.,Dahl,R.E.(2010).HealthyAdolescents’NeuralResponsetoReward:AssociationsWithPuberty,PositiveAffect,andDepressiveSymptoms.JournaloftheAmericanAcademyof
Child&AdolescentPsychiatry,49(2),162–172.9. Foti,D.,&Hajcak,G.(2009).Depressionandreducedsensitivitytonon-rewardsversus
rewards:Evidencefromevent-relatedpotentials.BiologicalPsychology,81(1),1–8.10. Foti,D.,&Hajcak,G.(2012).Geneticvariationindopaminemoderatesneuralresponse
duringrewardanticipationanddelivery:Evidencefromevent-relatedpotentials.Psychophysiology,49(5),617–626.
11. Foti,D.,Weinberg,A.,Bernat,E.M.,&Proudfit,G.H.(2015).Anteriorcingulateactivitytomonetarylossandbasalgangliaactivitytomonetarygainuniquelycontributetothefeedbacknegativity.ClinicalNeurophysiology,126(7),1338-1347.
12. Kujawa,A.,Proudfit,G.H.,&Klein,D.N.(2014).Neuralreactivitytorewardsandlossesinoffspringofmothersandfatherswithhistoriesofdepressiveandanxietydisorders.JournalofAbnormalPsychology,123(2),287–297.
13. Levinson,A.R.,Speed,B.C.,&Hajcak,G.(2016).ReliabilityoftheelectrocorticalresponsetogainsandlossesintheDoorstask.UnderReview.
14. Liu,W.,Wang,L.,Shang,H.,Shen,Y.,Li,Z.,Cheung,E.F.C.,&Chan,R.C.K.(2014).Theinfluenceofanhedoniaonfeedbacknegativityinmajordepressivedisorder.Neuropsychologia,53,213–220.
15. Luking,K.R.,Nelson,B.D.,Infantolino,Z.P.,Sauder,C.L.,&Hajcak,G.(underreview).InternalreliabilityoffMRIandEEGMeasuresofRewardinLateChildhoodandEarlyAdolescence.
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16. Nelson,B.D.,Perlman,G.,Klein,D.N.,Kotov,R.,&Hajcak,G.(inpress).BluntedNeuralResponsetoRewardsProspectivelyPredictstheDevelopmentofDepressioninAdolescentGirls.AmericanJournalofPsychiatry.
17. Parvaz,M.A.,Gabbay,V.,Malaker,P.,&Goldstein,R.Z.(2016).Objectiveandspecifictrackingofanhedoniaviaevent-relatedpotentialsinindividualswithcocaineusedisorders.DrugandAlcoholDependence.doi:10.1016/j.drugalcdep.2016.05.004
18. Plichta,M.M.,Schwarz,A.J.,Grimm,O.,Morgen,K.,Mier,D.,Haddad,L.,Meyer-Lindenberg,A.(2012).Test–retestreliabilityofevokedBOLDsignalsfromacognitive–emotivefMRItestbattery.NeuroImage,60(3),1746–1758.
19. Speed,B.C.,Nelson,B.D.,Auerbach,R.P.,Klein,D.N.,&Hajcak,G.(2016).DepressionRiskandElectrocorticalReactivityDuringSelf-ReferentialEmotionalProcessingin8to14Year-OldGirls.JournalofAbnormalPsychology.doi:10.1037/abn0000173
20. Weinberg,A.,&Shankman,S.A.(2016).BluntedRewardProcessinginRemittedMelancholicDepression.ClinicalPsychologicalScience.doi:10.1177/2167702616633158
21. Weinberg,A.,Liu,H.,Hajcak,G.,&Shankman,S.A.(2015).Bluntedneuralresponsetorewardsasavulnerabilityfactorfordepression:Resultsfromafamilystudy.JournalofAbnormalPsychology,124(4),878–889
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AppendixPVS-IIb:DetailedEvaluationCriteriaforMonetaryIncentiveDelayTask
PVSConstruct:RewardResponsiveness
PVSSub-construct:RewardAnticipation
1. Howvalidatestoftheconstructisthetask?Ok.
i.TheMIDtaskelicitsrobustandreliablebrainactivity(seebelow)duringanticipationofmonetarygainsinthenucleusaccumbens(NAcc)(3);duringanticipationofmonetarylossesintheanteriorinsula,andlessrobustbutstillreliableactivityinresponsetogainoutcomesinthemedialprefrontalcortex(MPFC)andputamen-possiblyduetosplittrials)(5).
ii.NAccactivityduringanticipationoflargegainsoftencorrelateswithcueelicitedpositivearousal(7).
iii.NAccactivityduringanticipationoflargegainsalsocorrelatesselectivelywithindividualdifferencesinpositivearousedtraits(r’s~.3)(4).
iv.NAccactivityduringanticipationoflargegainscorrelateswithnegativesymptomsacrossseveralstudiesofpatientswithschizophrenia(r’s~.5),butnotasrobustlywithsymptomsrelatedtoaffectivedisorders(10).
2. Doesthetaskhavegoodpsychometriccharacteristics(incl.highinternalreliability,test-
retestreliability,sensitivity/specificity,limitedpracticeeffects,availabilityofalternate
forms,longitudinalstability)?Yes.i.Internalreliability:Split–halfreliabilityofneuralactivityduringthefirsttestingsessionindicatedthatrightNAccactivityduringanticipationoflargegains(ICC=0.56/0.71,p<.05)wasmoderate(4)(unpublishedsupplement).
ii.Test-retestreliability:Test-retestreliabilityofneuralactivityovera>2yearperiodindicatedthatpeakrightNAccactivityduringanticipationoflargegains(ICC=0.64/0.78)andrightAInsactivityduringanticipationoflargelosses(ICC=.47/.64)wasmoderatetostrong(4)(otherconditionsshowedlesssignificanceandpeaksshowedbetterreliabilitythanfittedcontrasts).Similarly,otherneuroimagingstudiesusingcomparablerewardtasksdemonstratedgoodreliabilityiftheyusedlarge(6)butnotsmall(8)incentives.
iii.Measureswiththegreatesttest-retestreliabilitywerealsothemostcorrelatedwithaffectivetraits(r~.3),whilesignaltonoiseratiowasnot(4).
iv.Poweranalysisindicatedthatforlargeeffectsizes(f=3.07)typicallyobservedinNAccactivitycontrastsofanticipationoflargeversusnogains,6subjectsweresufficienttodetectagroupeffectatapowerof.80(p<.05).
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v.Alternateforms(i.e.,pseudorandomorders)areavailableandproduceindistinguishableresults.
vi.Developmentalstabilityoveradolescenceiscurrentlybeingassessedinlargesamples(e.g.,IMAGEN).
3. Areparametersforadministeringthetask(e.g.,numberoftrials,stimuluscharacteristics,
etc.)standardizedonanempiricalbasis?Somewhat.i.Design:ArecentandpopularversionoftheMIDtaskusesa2(valence:gain,loss)x3(magnitude:$0,$1,$5)factorialdesignwith15-18trialspercell.Orderispseudorandomandbalancedwitha2-6secondintertrialinterval.Cuefeaturescanandhaverepresenteddiversealternativeincentivefeaturesincludingprobability(9),requiredeffort(11)etc.
ii.Analysis:Anticipationcanandshouldbeseparatelyanalyzedfromoutcomes(whichareconditionalonandorthogonaltoanticipation).Rawaveragesofpeakactivationcanbeextractedandanalyzedandshowsuperiortest-retestreliabilitytocontrastsandresultingfits(4).
iii.Development:Taskparametersandrequirementscouldbenefitfromcontinuedoptimization,particularlywithrespecttobalancingtasklengthagainstpsychometriccriteria(i.e.,moreresearch/fundingisneeded).
4. Isthetaskfreefromfloor/ceilingeffectsthatcouldprecludeuseinsubjectswitharange
ofimpairment?Yes.i.TheMIDtaskavoidsfloorandceilingeffectsbyimplementinganadaptivetargetresponsewindowthatallowsittobeadministeredinmostsubjectpopulations,includingclinicalsamplesandacrossthelifespan(10)(14),whichcontrolstheexpectedvalueofcuesandoutcomesacrossdiversesamples.
5. Doesthetaskhavethesameperformancecharacteristicsacrosscultures?Isitfreefrom
culture-andlanguage-specificfeatures/stimuli?Yes.i.TheMIDtaskhasbeenappliedacrossdiversecultureswherefMRIisavailableandproducedqualitativelycomparableresults(e.g.,Britain,Germany,France,Netherlands,Israel,Japan,China,US,etc.)(12).Trainingsubjectswithabstractcueshelpscontrolpre-existingconfoundsduetolearningorpre-existingsymbolicassociations.Cuemappingscanalsobefullycounterbalancedwithindatasets.
ii.Abstractcuesfacilitatemappingincentivesaccordingtoculturallyequivalentincentiveschemes(e.g.,adaptingthesymbol$to€)tobedeterminedbyculturally-informedresearchers.
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6. Isthetasksensitivetochangeandlackandlossoffunction?Yes.i.Greaterage-relateddeclinesinAInsactivityduringanticipationoflargelossesversusNAccactivityduringanticipationoflargegainshasbeenreplicatedinmultiplestudies(14;15).
ii.SomeclinicalresearchsuggeststhatbluntedNAccactivityduringgainanticipationinschizophrenicpatientsontypicalantipsychoticscanpartiallybereversedafterswitchingtoatypicalantipsychotics,intandemwithdiminutionofnegativesymptoms(13).
7. Canthetask(oritsanalog)beusedinanimals?Yes(aftersubstitutingprimaryfor
secondaryrewards).i.Tasksthatvarycuedrewardmagnitude(i.e.,dropsofsugarwater)elicitmagnitude-dependentincreasesinNAccdopaminereleaseinrats,asassessedbyinvivocyclicvoltammetry(16)(thesameisnottrueforcuedeffort,parallelinghumanstudies).
8. Canthetaskbeusedacrossagegroups?Yes.
i.TheMIDtaskhasbeenusedinadolescentsandelders,andtokenizedversionshavebeenextendedtochildren(butrequirenorming).
ii.Adolescents(<18)showqualitativelysimilaractivitypatterns,withsomewhatdiminishedNAccactivityduringanticipationoflargegains(17;18).
iii.Olderadults(>60)typicallyshowsimilaractivityasyoungeradults,withtheexceptionoflessAInsactivityduringanticipationoflargelosses(4;14)
9. Canthetaskbeusedwithmethodstointerrogatebraincircuitry(e.g.,fMRI,EEG,etc.)?
Yes(particularlyFMRI).i.TheMIDtaskisspecificallydesignedandoptimizedforusewithFMRI.ii.TheMIDtaskhasbeenusedwithEEG,butdeepsourcesaredifficulttolocalize(6).iii.WearecurrentlyexploringconnectionswithraclopridedisplacementPETbutdisparatetimescalesaredifficulttocompare(butsee(19)).
10.Isthereconsensusonwhichmetric/scoreshouldbeconsideredtobeprimary?Somewhat.
i.Whilethereisnoformalconsensusforneuralactivity,themajorityofresearcherscontrast:(1)gainversusnongainanticipation;(2)lossversusnonlossanticipation;(3)gainversusnongainoutcome;(4)nonlossversuslossoutcome.Alternatively,researchersextractpeakactivationforallconditions(e.g.,valencebymagnitude)fromvolumesofinterestintheNAcc,MFPC,andrightAIns(recommended).(12)
ii.Valenceandarousalratingsforeachoftheincentivecuescanbecollectedafter(orevenduring)thetask,mean-deviated,androtatedtoderivecueelicitedpositivearousalandnegativearousalscores(20).
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iii.Functionalconnectivitybetweennodescouldbeextractedforspecifictrialphasesandconditions,buttheseindiceshavenotreceivedextensivepsychometriccharacterization(e.g.,(21)).
11.Areadequatenormativedataavailableacrossage,gender,education,ethnicity,SES?
Partially.i.Somenormativedataareavailableinmedium-sizedsamples(n=52)forageandgender(4),andlargerdatasetsarecomingonline(e.g.,IMAGEN).Samplestodatehavetendedtoincludehigheducationandsocioeconomicstatusindividuals(exceptincasesofclinicalgroups).
12.Aretherelationshipsbetweentaskperformanceandneuralsignal(s)known?Yes.i.Behavioralperformanceistypicallycontrolledsothatassociationsbetweenovertbehaviorandbrainactivityaredissociable.
ii.Regressorsthatparametricallymodelreactiontimeinresponsetoeachtarget,however,typicallyrobustlyactivatetheputamenandsupplementarymotorcortex(22).
13.Aretherelationshipsbetweentaskperformanceandclinicalfeature(s)known?
Somewhat.i.Behavioralperformanceistypicallycontrolledsothatassociationsbetweenovertbehaviorandbrainactivityaredissociable(asabove).
ii.ThestrongestclinicalcorrelatesofNAccactivityduringgainanticipationtodatehaveincludednegativesymptomsinthecontextofschizophrenia(23)andhyperactivesymptomsinthecontextofADHD(6;24).
iii.Manyotherdisordersremaintobeexplored(e.g.,affectivedisorders,addiction).
14.Isthetaskfeasibleforadministrationacrosssites?Yes.i.AnadaptedversionoftheMIDtaskhasbeenusedinapproximately2000youthacross8EuropeansitesintheIMAGENconsortium,andisalsobeingusedinanothermultisitestudy(FAST-MAS).Initialverificationofadequatesignalhomogeneityandspatiotemporalresolutionacrossscannersisessential.
15.Canthetaskbeusedasastand-alonebehavioraltask?Possiblynot.i.BecausetheMIDtaskadaptivelycontrolsperformancetoequateexpectedvalue,fasterreactiontimemeasurestoprovidelimitedinformation.
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ii.Researcherscan,however,solicitaffectiveresponses(typicallyvalenceandarousal)toincentivecuesasasummarymeasureofaffectiveresponsiveness(9).Combinationofneuralself-reportmeasures,however,isrecommended.
16.Whatworkisneededtogetthistaskreadyforuseinclinicaltrials?Inuse,butmorecouldbedone.i.Thecurrent“standard”3(magnitude)x2(valence)versionisalreadyinuseinmanyclinicalandpharmacologicalprotocols(however,seebelow):
ii.Thetaskinvolvesaspeededreactiontimeresponse.Thisiscontrolledacrossincentiveconditions,butmayaddtotheobservedsignal.Ifreducedmotorengagementisdesired,aMIDtaskversioninvolvingchoicesratherthanspeededreactiontimecouldbecomparedwithcanonicalversions(thiswouldrequirepiloting,however,sinceitcouldchangetheaffectiveresponsesandgeneralizabilityofthetask).
iii.Moreextensivesetsofgainandlossmagnitudescouldbeinvestigatedinalongerexperimenttodetermineoptimalmagnitudes(however,seteffectsmayalsoplayarole).
iv.Adirectlyparallelversioncouldbedevisedandcharacterizedinratsusingbotholder(voltammetry)andnewer(optogeneticfiberphotometry)measures,possiblyalongsidepharmacologicalmodulationforvalidation.
v.Fasterperipheralphysiologicalmeasures(facialelectromyography+pupillarydilation)mightbetestedasapotentiallydilutedbutimplicitbehavioralprobeofaffectiveresponsesduringtheMIDtask.
vi.Taskparameters(i.e.,numberandcompositionofconditions,numberoftrialspercondition,minimumvariableintertrialinterval)couldbecomparedandoptimizedinaseriesoftrials.
17.Isthetaskcopyrighted?No.
i.InitialdevelopmentoftheMIDTaskwasfundedthroughanNIHB/STARTgrantMH066923sothetaskbelongstoAmericantaxpayers.Versioncontrol,however,ismaintainedbyBK([email protected]),whocanproviderecentcopiesofthetaskuponrequest.
References
1. KnutsonB,Westdorpa,KaiserE,HommerD(2000):FMRIvisualizationofbrainactivityduringamonetaryincentivedelaytask.Neuroimage12:20–7.
2. HaberSN,KnutsonB(2010):Therewardcircuit:linkingprimateanatomyandhumanimaging.Neuropsychopharmacology35:4–26.
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3. KnutsonB,AdamsCM,FongGW,HommerD(2001):Anticipationofincreasingmonetaryrewardselectivelyrecruitsnucleusaccumbens...JNeurosci(Vol.21).doi:20015472[pii].
4. WuCC,Samanez-LarkinGR,KatovichK,KnutsonB(2014):Affectivetraitslinktoreliableneuralmarkersofincentiveanticipation.Neuroimage84:ElsevierInc.279–289.
5. KnutsonB,FongGW,BennettSM,AdamsCM,HommerD(2003):Aregionofmesialprefrontalcortextracksmonetarilyrewardingoutcomes:characterizationwithrapidevent-relatedfMRI.Neuroimage18:263–272.
6. PlichtaMM,ScheresA(2014):Ventral-striatalresponsivenessduringrewardanticipationinADHDanditsrelationtotraitimpulsivityinthehealthypopulation:Ameta-analyticreviewofthefMRIliterature.NeurosciBiobehavRev38:125–134.
7. KnutsonB,GreerSM(2008):Anticipatoryaffect:Neuralcorrelatesandconsequencesforchoice.PhilosTransRSocLondBBiolSci363:3771–86.
8. FliessbachK,RoheT,LinderNS,TrautnerP,ElgerCE,WeberB(2010):Retestreliabilityofreward-relatedBOLDsignals.Neuroimage50:ElsevierInc.1168–1176.
9. KnutsonB,TaylorJ,KaufmanM,PetersonR,GloverG(2005):Distributedneuralrepresentationofexpectedvalue.JNeurosci25:4806–4812.
10. KnutsonB,HeinzA(2015):Probingpsychiatricsymptomswiththemonetaryincentivedelaytask.BiolPsychiatry77:418–20.
11. CroxsonPL,WaltonME,O’ReillyJX,BehrensTEJ,RushworthMFS(2009):Effort-basedcost-benefitvaluationandthehumanbrain.JNeurosci29:4531–41.
12. BalodisIM,PotenzaMN(2015):Anticipatoryrewardprocessinginaddictedpopulations:Afocusonthemonetaryincentivedelaytask.BiolPsychiatry77:Elsevier434–444.
13. SchlagenhaufF,JuckelG,KoslowskiM,KahntT,KnutsonB,DemblerT,etal.(2008):Rewardsystemactivationinschizophrenicpatientsswitchedfromtypicalneurolepticstoolanzapine.Psychopharmacology(Berl)196:673–684.
14. Samanez-LarkinGR,GibbsSEB,KhannaK,NielsenL,CarstensenLL,KnutsonB(2007):Anticipationofmonetarygainbutnotlossinhealthyolderadults.NatNeurosci10:787–791.
15. Samanez-LarkinGR,LevensSM,PerryLM,DoughertyRF,KnutsonB(2012):Frontostriatalwhitematterintegritymediatesadultagedifferencesinprobabilisticrewardlearning.JNeurosci32:5333–7.
16. GanJO,WaltonME,PhillipsPEM(2010):Dissociablecostandbenefitencodingoffuturerewardsbymesolimbicdopamine.NatNeurosci13:25–7.
17. BjorkJM,KnutsonB,FongGW,CaggianoDM,BennettSM,HommerDW(2004):Incentive-elicitedbrainactivationinadolescents:similaritiesanddifferencesfromyoungadults.JNeurosci24:1793–1802.
18. BjorkJM,KnutsonB,HommerDW(2008):Incentive-elicitedstriatalactivationinadolescentchildrenofalcoholics.Addiction103:1308–1319.
19. SchottBH,MinuzziL,KrebsRM,ElmenhorstD,LangM,WinzOH,etal.(2008):Mesolimbicfunctionalmagneticresonanceimagingactivationsduringrewardanticipationcorrelatewithreward-relatedventralstriataldopaminerelease.JNeurosci28:14311–9.
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20. KnutsonB,KatovichK,SuriG(2014):InferringaffectfromfMRIdata.TrendsCognSci18:422–8.
21. ChoYT,ErnstM,FudgeJL(2013):Cortico-amygdala-striatalcircuitsareorganizedashierarchicalsubsystemsthroughtheprimateamygdala.JNeurosci33:14017–30.
22. KnutsonB,TaylorJ,KaufmanM,PetersonR,GloverG(2005):Distributedneuralrepresentationofexpectedvalue.JNeurosci25:4806–12.
23. JuckelG,SchlagenhaufF,KoslowskiM,WüstenbergT,VillringerA,KnutsonB,etal.(2006):Dysfunctionofventralstriatalrewardpredictioninschizophrenia.Neuroimage29:409–16.
24. ScheresA,MilhamMP,KnutsonB,CastellanosFX(2007):Ventralstriatalhyporesponsivenessduringrewardanticipationinattention-deficit/hyperactivitydisorder.BiolPsychiatry61:720–724.
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AppendixPVS-IIc:DetailedEvaluationCriteriaforDevaluationLearningTasks
PVSConstruct:RewardLearning
PVSSub-construct:Habit
1. Howvalidatestoftheconstructisthetask?
Devaluationlearningtasks(DLT)weredevelopedtoprovideanobjectivemeasureofparticipants’abilitytoestablishahabitualresponsetostimuliassociatedwithoutcomesthatearnpoints,andthena‘slips-of-action’phasemeasurestheirabilitytonotrespondtoformerlyrewardedstimulithataredevaluedinthefinaltestphase.Priorstudieshaveshownthatdevaluationlearning:
1) isnegativelycorrelatedwithticseverityinpatientswithGillesdelaTouretteSyndrome(Delormeetal.2016),OCDtraits(Snorrasonetal.2016)inyoungadults,andbluntedinpatientswithOCD(Gillanetal.2011)andpatientswithalcoholdependence(Sjoerdsetal.2013).MedicatedpatientswithGillesdelaTouretteSyndromeshowedimproveddevaluationlearningovernon-medicatedpatients(Delormeetal.2016).Patientswithlongerdurationofalcoholdependenceshowedlessengagementoftheventromedialprefrontalcortex(acriticalstructureforgoal-directedbehaviorthatcanoverridehabitualbehavior)(Sjoerdsetal.2013).
2) isbluntedwithacutedopamine(deWitetal.2012)andtryptophandepletion(Worbeetal.2015),andsteeperdeclinesinplasmatryptophanlevelspredictedpoorerperformanceindevaluingstimuli(Worbeetal.2015)
3) islinkedtoreward-relatedactivation(deWitetal.2009)inhumansandrats(Smith&Graybiel2016)(dorsalstriatum)andatypicalstructuralconnectivityfromrewardnodestomotorregions(Delormeetal.2016)inpatientswithGillesdelaTouretteSyndrome.
2. Doesthetaskhavegoodpsychometriccharacteristics(incl.highinternalreliability,test-
retestreliability,sensitivity/specificity,limitedpracticeeffects,availabilityofalternate
forms,longitudinalstability)?
i. highinternalreliability:notevaluatedii. test-retestreliability:notevaluatediii. Sensitivity/specificity:notevaluatediv. Limitedpracticeeffects:notevaluatedv. Availabilityofalternateforms:notevaluatedbutpossiblevi. Longitudinalstability:notevaluated
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3. Areparametersforadministeringthetask(e.g.,numberoftrials,stimuluscharacteristics,
etc.)standardizedonanempiricalbasis?
i. No.Parametersneedtobeoptimizedforadministrationacrossadult,pediatric,andclinicalpopulations.
4. Isthetaskfreefromfloor/ceilingeffectswhichwouldprecludeuseinsubjectswitha
rangeofimpairment?
i. Incomplete;taskcharacteristicsshowadequatevariabilityacrosshealthyadultandadultclinicalpopulations,butadditionalworkisneededforpediatricpopulations.
5. Doesthetaskhavethesameperformancecharacteristicsacrosscultures?Isitfreefrom
culture-andlanguage-specificfeatures/stimuli?
i. Notyetknown
6. Isthetasksensitivetochangeandlackandlossoffunction?
i. Yes,asevidencedbypsychopharmacologicchallenge(Worbeetal.2015;deWitetal.2012)andfindingsinpatientpopulations(Sjoerdsetal.2013;Gillanetal.2011;Delormeetal.2016).
7. Canthetask(oritsanalog)beusedinanimals?
i. Incomplete–onestudytodateshowseffectiveanimalanalog(Smith&Graybiel2016).
8. Canthetaskbeusedacrossagegroups?
i. Versionsimplementedinadults(Snorrasonetal.2016;Sjoerdsetal.2013;Delormeetal.2016;Gillanetal.2011;deWitetal.2012;Worbeetal.2015),olderadults(deWitetal.2011),andchildren(Geurts&deWit2013),butthechildhoodtaskdidnotelicittheintendeddevaluationeffectinchildrenwithautism.Unclearifthisisbecausehabitformationisintactinchildrenwithautismorthetaskwasnotproperlyoptimizedtobesensitivetodifferencesinperformanceforchildren—existingdataonrewardsystems(Kohlsetal.2012;Dichteretal.2012)andreversallearninginautism(Yerysetal.2009;D’Cruzetal.2013;Reedetal.2011)wouldsuggestdevaluationlearningtobeareasonabletargettoexpectdifferencesbetweengroups.
9. Canthetaskbeusedwithmethodstointerrogatebraincircuitry(e.g.,fMRI,EEG,etc.)?
i. Yes(seeabove).ThetaskhasbeenimplementedwithfMRIandDTI(deWitetal.2009;Delormeetal.2016)
10. Isthereconsensusonwhichmetric/scoreshouldbeconsideredtobeprimary?
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i. Differencescoreofvaluableminusdevaluedresponse%inSlips-of-ActionandBaselinephases
ii. Correct/IncorrectresponsesanddecreasesinRToverthecourseofthelearningphaseiii. AccuracyduringtheOutcome-devaluationstage
11. Areadequatenormativedataavailableacrossage,gender,education,ethnicity,SES?
i. No
12. Aretherelationshipsbetweentaskperformanceandneuralsignal(s)known?
i. Yes(seeabove).Linkagetostriatuminhumans(Delormeetal.2016;deWitetal.2009)andanimals(Smith&Graybiel2016).
13. Aretherelationshipsbetweentaskperformanceandclinicalfeature(s)known?
i. Yes,correlateswithticseverityinGillesdelaTouretteSyndrome(Delormeetal.2016)andpoorerdevaluationobservedinpatientswithOCD(Gillanetal.2011)andalcoholdependence(Sjoerdsetal.2013)butnotParkinson’s(deWitetal.2011)orautism(Geurts&deWit2013).
14. Isthetaskfeasibleforadministrationacrosssites?
i. Yes
15. Canthetaskbeusedasastand-alonebehavioraltask?i. Yes
16. Whatworkisneededtogetthistaskreadyforuseinclinicaltrials?
i. Optimizationacrosspediatricandclinicalpediatricpopulations,validityandnormalizationanalyses.
17. Isthetaskcopyrighted?i. No
References:
1.Delorme,C.etal.EnhancedhabitformationinGillesdelaTourettesyndrome.Brain139,605–615(2016).
2.Snorrason,I.,Lee,H.J.,deWit,S.&Woods,D.W.Arenonclinicalobsessive-compulsivesymptomsassociatedwithbiastowardhabits?PsychiatryRes.241,221–223(2016).
3.Gillan,C.M.etal.Disruptioninthebalancebetweengoal-directedbehaviorandhabitlearninginobsessive-compulsivedisorder.Am.J.Psychiatry168,718–726(2011).
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4.Sjoerds,Z.etal.Behavioralandneuroimagingevidenceforoverrelianceonhabitlearninginalcohol-dependentpatients.Transl.Psychiatry3,e337(2013).
5.deWit,S.etal.Relianceonhabitsattheexpenseofgoal-directedcontrolfollowingdopamineprecursordepletion.Psychopharmacology(Berl.)219,621–631(2012).
6.Worbe,Y.,Savulich,G.,Wit,S.de,Fernandez-Egea,E.&Robbins,T.W.TryptophanDepletionPromotesHabitualoverGoal-DirectedControlofAppetitiveRespondinginHumans.Int.J.Neuropsychopharmacol.18,pyv013(2015).
7.deWit,S.,Corlett,P.R.,Aitken,M.R.,Dickinson,A.&Fletcher,P.C.DifferentialEngagementoftheVentromedialPrefrontalCortexbyGoal-DirectedandHabitualBehaviortowardFoodPicturesinHumans.J.Neurosci.29,11330–11338(2009).
8.Smith,K.S.&Graybiel,A.M.Habitformationcoincideswithshiftsinreinforcementrepresentationsinthesensorimotorstriatum.J.Neurophysiol.115,1487–1498(2016).
9.deWit,S.,Barker,R.A.,Dickinson,A.D.&Cools,R.HabitualversusGoal-directedActionControlinParkinsonDisease.J.Cogn.Neurosci.23,1218–1229(2011).
10.Geurts,H.M.&deWit,S.Goal-directedactioncontrolinchildrenwithautismspectrumdisorders.Autism18,409–18(2013).
11.Kohls,G.,Chevallier,C.,Troiani,V.&Schultz,R.T.Social‘wanting’dysfunctioninautism:neurobiologicalunderpinningsandtreatmentimplications.J.Neurodev.Disord.4,10(2012).
12.Dichter,G.S.,Damiano,C.A.&Allen,J.A.Rewardcircuitrydysfunctioninpsychiatricandneurodevelopmentaldisordersandgeneticsyndromes:animalmodelsandclinicalfindings.J.Neurodev.Disord.4,19(2012).
13.Yerys,B.E.etal.Set-shiftinginchildrenwithautismspectrumdisorders:reversalshiftingdeficitsontheIntradimensional/ExtradimensionalShiftTestcorrelatewithrepetitivebehaviors.Autism13,523–538(2009).
14.D’Cruz,A.-M.etal.Reducedbehavioralflexibilityinautismspectrumdisorders.Neuropsychology27,152–160(2013).
15.Reed,P.,Watts,H.&Truzoli,R.Flexibilityinyoungpeoplewithautismspectrumdisordersonacardsorttask.Autism(2011).doi:10.1177/1362361311409599
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AppendixPVS-IId:DetailedEvaluationCriteriaforProbabilisticRewardTask
PVSConstruct:RewardLearning
PVSSub-construct:ProbabilisticandReinforcementLearning
1. Howvalidatestoftheconstructisthetask?
TheProbabilisticRewardtask(PRT)wasdevelopedtoprovideanobjectivemeasureofparticipants’abilitytomodifybehaviorasafunctionofreward(Pizzagallietal.2005)(modifiedafter(Tripp&Alsop1999)),andyieldsmeasuresofrewardresponsivenessandrewardlearning.Priorstudieshaveshownthatresponsebiastowardsamorefrequentlyrewardedstimulus:
(1)isinverselyrelatedtocurrentanhedonicsymptomsinunselectedadults,individualswithelevateddepressivesymptoms,andunmedicatedindividualswithcurrentMDD(Pizzagalli,Iosifescu,etal.2008;Pizzagallietal.2005;Bogdan&Pizzagalli2006)andrelativesofpatientswithmajordepression(W.-H.Liuetal.2016);correlateswithreducedhedoniccapacity/approachmotivationprepubertalchildren(Lukingetal.2015);andcorrelateswithcigarettecravingamongsmokers(Peechatkaetal.2015);
(2)predictsself-reportedanhedonicsymptoms38dayslater(Pizzagallietal.2005);(3)isbluntedinindividualswithincreaseddepressivesymptoms,currentMDD,andpast
MDD(Pizzagalli,Iosifescu,etal.2008;Pizzagallietal.2005;Pechteletal.2013;Whittonetal.2016;Liuetal.2011),particularlythosewithelevatedanhedonicsymptoms(Vrieze,Pizzagalli,etal.2013)ormelancholicdepression(Fletcheretal.2015);inrelativesofpatientswithmajordepressionwithsub-clinicaldepressivesymptoms(W.-H.Liuetal.2016);andinyouthreportinganhedoniaacrossvariousDSMdiagnosis(Morrisetal.2015).
(4)isimprovedbypharmacologicaltreatmentsamongdepressedinpatients(Vrieze,Pizzagalli,etal.2013)andbyresidentialtreatmentinfemaleadolescentswithco-occurringdepressionandsubstanceabuse(Bogeretal.2014);
(5)islinkedtobothresting(Webbetal.2016)(Kaiseretal.,underreview)andreward-relatedactivationandfunctionalconnectivitywithinnodesofthebrainrewardsystem(ventral/dorsalstriatum,orbitofrontalcortex,dorsalanteriorcingulatecortex)(Santessoetal.2008a;Santessoetal.2009;Bogdanetal.2011)aswellasERPmarkersofreinforcementlearning(Santessoetal.2008a;Whittonetal.2016;Bress&Hajcak2013);
(6)islinkedtoDAreleaseinextrastriatalregions(asassessedbyPET)(Vrieze,Ceccarini,etal.2013);
(7)isassociatedwithgeneticvariantsknowntomodulateprefrontaldopaminergicvariation(COMT;(Lancasteretal.2012;Lancasteretal.2015;Goetzetal.2013);and(Corral-Fríasetal.2016),riskformooddisordersandschizophrenia(CACNA1C;(Lancasteretal.2014),andmu-opioidreceptorfunction(Leeetal.2011).
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(8)ispotentiatedorbluntedbypharmacologicalchallengeshypothesizedtoincrease(e.g.,nicotine,amphetamine)ordecrease(e.g.,singlelowdosesofpramipexolethoughttoreducephasicDAresponseviapresynapticautoreceptoractivation),respectively,DAsignalinginbothhumansandrats(Barretal.2008;Pizzagalli,Evins,etal.2008;Pergadiaetal.2014;Der-Avakianetal.2013);
(9)ispotentiatedinhealthycontrolsbyhigh-frequencyrapidTMSovertheleftdorsolateralprefrontalcortex(Ahnetal.2013);
(10)isbluntedbyacutelaboratoryandprolongednaturalisticstressors(Bogdan&Pizzagalli2006;Pizzagallietal.2007),particularlyinindividualscarryinggeneticvariantspreviouslyassociatedwithincreasedHPAreactivityordepression(Bogdanetal.2011;Bogdanetal.2010;Nikolovaetal.2012);conversely,agreaterresponsebiasunderstressamongindividualswithGeneralAnxietyDisorders(GAD)predictslowerdepressionsymptoms1monthlater(Morris&Rottenberg2015).
(11)isheritable(46%)(Bogdan&Pizzagalli2009).
2. Doesthetaskhavegoodpsychometriccharacteristics(incl.highinternalreliability,test-
retestreliability,sensitivity/specificity,limitedpracticeeffects,availabilityofalternate
forms,longitudinalstability)?
i. highinternalreliability:notevaluatedii. test-retestreliability:0.57over38daysinunselectedindividuals(Pizzagallietal.2005);
replicatedinanindependentunselectedsample:r=0.50-0.56over39days(Santessoetal.2008b)
iii. Sensitivity/specificity:ROCanalysesnotperformedyet(butdataareavailable)iv. Limitedpracticeeffects:minimizedbyusingdifferentalternateforms(seebelow).v. Availabilityofalternateforms:Yes(5forms)vi. Longitudinalstability:limited(onlyevaluatedover~40days)
3. Areparametersforadministeringthetask(e.g.,numberoftrials,stimuluscharacteristics,
etc.)standardizedonanempiricalbasis?
i. Taskcharacteristics(e.g.,stimulussizeandexposure)wereoptimizedinordertoachieveanoverallaccuracy~0.85(toallowconditionorgroupmodulations).
4. Isthetaskfreefromfloor/ceilingeffectswhichwouldprecludeuseinsubjectswitha
rangeofimpairment?
i. Yes;taskcharacteristics(e.g.,stimulussizeandexposure)wereoptimizedinordertoachieveanoverallaccuracy~0.85.
5. Doesthetaskhavethesameperformancecharacteristicsacrosscultures?Isitfreefrom
culture-andlanguage-specificfeatures/stimuli?
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i. FindingsofreducedresponsebiasinMDDvs.healthycontrolshavebeenreplicatedacrossUS(Pizzagalli,Iosifescu,etal.2008),European(Vrieze,Pizzagalli,etal.2013),andAsian(Liuetal.2011)samples.Thetaskanditsinstructionshavebeentranslatedinseverallanguages(e.g.,Dutch,English,German,Korean,Chinese)
ii. Thetaskhasbeenfreelydisseminatedby>110researchgroupsacrossmanycountries;itsminimalrelianceonverbalstimulimakescross-culturalcomparisonsfeasible.
6. Isthetasksensitivetochangeandlackandlossoffunction?
i. Yes,asevidencedbypharmacologicalchallenges(Barretal.2008;Pizzagalli,Evins,etal.2008;Pergadiaetal.2014),neurostimulation(Ahnetal.2013),andfindingsinpatientsamples(Pizzagalli,Iosifescu,etal.2008;Fletcheretal.2015;Vrieze,Pizzagalli,etal.2013;Liuetal.2011).
7. Canthetask(oritsanalog)beusedinanimals?
i. Yes;aconceptuallyanalogousversionhasbeendevelopedforrats(Der-Avakianetal.2013).Cross-speciesstudieshaveshownthatthesamefindingshaveemergedinhumansandratswhenusingpharmacologicalchallenges(Pizzagalli,Evins,etal.2008;Der-Avakianetal.2013),nicotinewithdrawal(Pergadiaetal.2014),orstressors(Bogdan&Pizzagalli2006)(andDer-Avakianetal.,inpreparation).
8. Canthetaskbeusedacrossagegroups?
i. Some(unpublished)datainchildren
9. Canthetaskbeusedwithmethodstointerrogatebraincircuitry(e.g.,fMRI,EEG,etc.)?
i. Yes(seeabove).ThetaskhasbeenusedinconjunctionwithERP,fMRIandPET.
10. Isthereconsensusonwhichmetric/scoreshouldbeconsideredtobeprimary?
i. Responsebiasii. Rewardlearning(e.g.,RB(block3)–RB(Block1)iii. Secondary:Discriminability,accuracy,RT
11. Areadequatenormativedataavailableacrossage,gender,education,ethnicity,SES?
i. Thetaskhasbeenadministeredtoover1,000individuals.Age-andgender-relatednormsareavailable.
12. Aretherelationshipsbetweentaskperformanceandneuralsignal(s)known?
i. Yes(seepoint#1)
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13. Aretherelationshipsbetweentaskperformanceandclinicalfeature(s)known?
i. Yes(seepoint#1)
14. Isthetaskfeasibleforadministrationacrosssites?
i. Yes(standardizationandamanualhavebeendevelopedfortheEMBARCstudy).ii. Inaddition,Dr.Pizzagalli’slabhasfeelyprovidedthetasktoover110groupssince
2005,andextensivedocumentation/manualsareavailableforstandardizationacrosssites.
15. Canthetaskbeusedasastand-alonebehavioraltask?
i. Yes
16. Whatworkisneededtogetthistaskreadyforuseinclinicaltrials?
i. EMBARCandCNTRACSwillprovideinforegardingitsuseinclinicaltrials
17. Isthetaskcopyrighted?i. Thecodeiscopyrighted(HarvardUniversity)andisprovidedforfreetoacademic
groups.Alicenseagreementisrequiredforindustry.
References:
Seeoverallbibliography
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AppendixPVS-IIe:DetailedEvaluationCriteriaforRiskandAmbiguityTask
PVSConstruct:RewardValuation
PVSSub-construct:Reward(probability)
1. Howvalidatestoftheconstructisthetask?
TheRiskandAmbiguityTaskwasdevelopedtoassessindividualbehaviorunderuncertainty.Itassessesindividualattitudestowardsrisk(knownoutcomeprobabilities)andambiguity(unknownoutcomeprobabilities)1,2.Thetaskyieldsmeasuresofriskandambiguityattitudesinthegainandlossdomains,aswellasmeasuresofdecisionquality3.Priorstudieshaveshown:
1) Decreasedambiguityaversioninadolescentscomparedtoadults4,whichincreaseswithage5.Noambiguityaversioninpre-adolescentchildren6.
2) Increasedriskaversioninthegaindomainandriskseekinginthelossdomain,aswellasdecreaseddecisionquality,inolderadults3.
3) IncreasedaversiontoambiguouslossesinindividualswithPTSD,whichiscorrelatedwithsymptomstrengthandmediatestheassociationbetweenthedegreeofcombatexposureandthedegreeofsymptoms,specificallyanxiousarousal7.
4) DecreaseddecisionqualityandincreasedambiguityaversioninindividualswithOCD8.5) Correlationbetweenthegray-mattervolumeofaregioninrightPosteriorParietal
Cortexandindividualrisktolerance9.6) Effectofindividualriskandambiguityattitudesonactivationmagnitudeinvalue-
relatedbrainareas1.
2. Doesthetaskhavegoodpsychometriccharacteristics(incl.highinternalreliability,test-
retestreliability,sensitivity/specificity,limitedpracticeeffects,availabilityofalternate
forms,longitudinalstability)?
i. highinternalreliability:notevaluatedii. test-retestreliability:riskandambiguityattitudesstablein18subjectsacrosstwo
sessionsseparatedbyseveraldays1,butreliabilitynotquantified.iii. Sensitivity/specificity:notevaluatediv. Limitedpracticeeffects:notevaluatedv. Availabilityofalternateforms:severalversionsofthetaskhavebeenusedvi. Longitudinalstability:notevaluated
3. Areparametersforadministeringthetask(e.g.,numberoftrials,stimuluscharacteristics,
etc.)standardizedonanempiricalbasis?
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i. No
4. Isthetaskfreefromfloor/ceilingeffectswhichwouldprecludeuseinsubjectswitha
rangeofimpairment?
i. Thetaskhasbeenusedinawiderangeofages,includingseveralpsychiatricconditions(seeabove),withnofloor/ceilingeffects.
5. Doesthetaskhavethesameperformancecharacteristicsacrosscultures?Isitfreefrom
culture-andlanguage-specificfeatures/stimuli?
i. Thetaskisfreefromculture-andlanguage-specificstimuli.Performanceacrossculturesnotevaluated.
6. Isthetasksensitivetochangeandlackandlossoffunction?
i. Notevaluated
7. Canthetask(oritsanalog)beusedinanimals?
i. Inprinciplethetaskisspecifictohumans,asitrequiresunderstandingofsymbolicprobabilities.Onestudy,however,usedananaloginmonkeys10.
8. Canthetaskbeusedacrossagegroups?
i. Yes,thetaskhasbeensuccessfullyusedacrossawiderangeofages,from8to90yearsold3-6.
9. Canthetaskbeusedwithmethodstointerrogatebraincircuitry(e.g.,fMRI,EEG,etc.)?
i. Yes,thetaskhasbeenusedwithfMRI1.
10. Isthereconsensusonwhichmetric/scoreshouldbeconsideredtobeprimary?
i. Riskandambiguityattitudesinthegainandlossdomains,estimatedbasedonproportionofchoicesofeachtype,orbasedonfittingabehavioralmodel
i. Estimatesofdecisionqualitybasedonviolationsoffirst-orderstochasticdominanceandtransitivity
11. Areadequatenormativedataavailableacrossage,gender,education,ethnicity,SES?
i. No
12. Aretherelationshipsbetweentaskperformanceandneuralsignal(s)known?
i. Onlypartially(seeabove)
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13. Aretherelationshipsbetweentaskperformanceandclinicalfeature(s)known?
i. Relationshipswithsomefeatures,includingobsessivecompulsivedisorderandanxiousarousalareknown(seeabove)
14. Isthetaskfeasibleforadministrationacrosssites?
i. Yes.Itincludesstandardizedinstructionsandhasbeenusedinamulti-sitestudyatYaleandNYU3,4.Thetaskwasalsoprovideduponrequesttoseveralothergroups.
15. Canthetaskbeusedasastand-alonebehavioraltask?
i. Yes.
16. Whatworkisneededtogetthistaskreadyforuseinclinicaltrials?
i. Standardizationofparameters,estimationoftheminimaltasklengthrequiredforadequateparameterestimates.
17. Isthetaskcopyrighted?i. No
References
1. LevyI,SnellJ,NelsonAJ,RustichiniA,GlimcherPW.Neuralrepresentationofsubjectivevalueunderriskandambiguity.JNeurophysiol.2010;103(2):1036-1047.
2. LevyI,RosenbergBelmakerL,MansonK,TymulaA,GlimcherPW.MeasuringthesubjectivevalueofriskyandambiguousoptionsusingexperimentaleconomicsandfunctionalMRImethods.JVisExp.2012(67):e3724.
3. TymulaA,RosenbergBelmakerLA,RudermanL,GlimcherPW,LevyI.Likecognitivefunction,decisionmakingacrossthelifespanshowsprofoundage-relatedchanges.ProcNatlAcadSciUSA.2013;110(42):17143-17148.
4. TymulaA,RosenbergBelmakerLA,RoyAK,etal.Adolescents'risk-takingbehaviorisdrivenbytolerancetoambiguity.ProcNatlAcadSciUSA.2012;109(42):17135-17140.
5. BlankensteinNE,CroneEA,vandenBosW,vanDuijvenvoordeAC.DealingWithUncertainty:TestingRisk-andAmbiguity-AttitudeAcrossAdolescence.DevNeuropsychol.2016:1-16.
6. LiR,BrannonEM,HuettelSA.Childrendonotexhibitambiguityaversiondespiteintactfamiliaritybias.FrontPsychol.2014;5:1519.
7. RudermanL,EhrlichDB,RoyA,PietrzakRH,Harpaz-RotemI,LevyI.PosttraumaticStressSymptomsandAversiontoAmbiguousLossesinCombatVeterans.DepressAnxiety.2016.
8. PushkarskayaH,TolinD,RudermanL,etal.Decision-makingunderuncertaintyinobsessive-compulsivedisorder.JPsychiatrRes.2015;69:166-173.
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9. Gilaie-DotanS,TymulaA,CooperN,KableJW,GlimcherPW,LevyI.Neuroanatomypredictsindividualriskattitudes.JNeurosci.2014;34(37):12394-12401.
10. HaydenBY,HeilbronnerSR,PlattML.Ambiguityaversioninrhesusmacaques.FrontNeurosci.2010;4.
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AppendixPVS-IIf:DetailedEvaluationCriteriafortheEffort-ExpenditureforRewardsTask
PVSConstruct:RewardValuation
PVSSub-construct:Effort
1. Howvalidatestoftheconstructisthetask?
TheEffortExpenditureforRewardsTask(EEfRT;pronounced“Effort”)wasdevelopedasahomologuetowell-studiedeffort-baseddecision-makingtasksusedintherodentliterature(e.g.,1).Thetaskassessesanindividualpreferencebetweenexpendinggreaterphysicaleffortintheformofspeededbuttonpressesinordertogainlargermonetaryrewardsvs.lesseffortforsmallerrewards.Thetasktakesapproximately20minutes,duringwhichtimeindividualstypicallycompleteapproximately50trialsforwhichtheymustchoosebetween“hardtasks”and“easytasks”.Trialsvaryintermsofboththemagnitudeofrewardavailableforchoosingthemoreeffortfuloptionaswellastheprobabilityofrewardreceipt.Thesemanipulationswereincludedtoincreasetheecologicalvalidityofthetaskforuseinhumans,buttheirinclusionmeansthatthetaskisnota“pure”measureofeffortalone.
(1)Consistentwithpredictionsfromtheanimalliteratureregardingtheroleofdopamine(DA)ineffort-baseddecision-making2,administrationoftheDA-releasingagentd-amphetamineincreasestheproportionofhard-tasksselectedontheEEfRT3.Additionallytheproportionofhard-taskspredictsamphetamine-inducedDAreleaseinthestriatum4.
(2)Proportionofhard-tasksisinverselyrelatedtotraitanhedoniainanundergraduatesampleenrichedforanhedonia5;andpositivelyrelatedtotraitrewardanticipationandbehavioralactivation6(andunpublishedobservations);
(3)Repeatedstudiesofpatientsindepression7,8andschizophrenia9-13;havefoundevidenceforalteredperformanceontheEEfRTascomparedtohealthycontrols.Importantlyhowever,itremainsunclearwhetherbothgroupsshowaprimaryreductionineffortexpenditure(preferenceforlesseffortfuloptions)oradeficitineffortallocation(exertinggreatereffortfortrialsthatofferrelativelysmallerrewards,andfailingtoexpendeffortfortrialsthatoffergreaterrewards).Furtherwithinthesegroups,relationshipsbetweenEEfRTperformanceanddimensionalmeasuresofanhedoniaornegativesymptomshavebeenmoderateatbest,andofteninconsistent,suggestingthattheymaybeassessingdifferentaspectsofreward-relatedsymptoms.
2. Doesthetaskhavegoodpsychometriccharacteristics(incl.highinternalreliability,test-
retestreliability,sensitivity/specificity,limitedpracticeeffects,availabilityofalternate
forms,longitudinalstability)?
i. highinternalreliability:evaluationinprocess;willbeavailableinwinter2016
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ii. test-retestreliability:assessedinasampleofschizophreniapatientsonly.ICCsat4weeksrangeinthissamplevariedfordifferentparameters(rewardmagnitude;probability).Rangefrom.079to0.53.
iii. Sensitivity/specificity:unknowniv. Limitedpracticeeffects:repeatedassessmentshavenotfoundsignificantevidenceof
practiceeffects3,14.v. Availabilityofalternateforms:Yes–awidenumberofvariantsarecurrentlyinusevi. Longitudinalstability:limited(onlyevaluatedfor~30days)
3. Areparametersforadministeringthetask(e.g.,numberoftrials,stimuluscharacteristics,
etc.)standardizedonanempiricalbasis?
i. Partially.Taskparametersaresettofacilitatehighcompletionrates(>90%)ofhighandloweffortoptioninhealthyormild/moderatepsychiatricpatients.
4. Isthetaskfreefromfloor/ceilingeffectswhichwouldprecludeuseinsubjectswitha
rangeofimpairment?
i. Partially.Somesubjectswillmakeallofonechoicetype(i.e.,alleasyorallhardchoices).Thisisestimatedtooccur<5%basedinhealthyparticipants,butmaybemoreprevalentinpatientpopulationswithvaryingimpairments.
5. Doesthetaskhavethesameperformancecharacteristicsacrosscultures?Isitfreefrom
culture-andlanguage-specificfeatures/stimuli?
i. FindingsintheUS8havebeenreplicatedinanindependently-collectedChinesesample7.
ii. Thetaskhasbeenshared>85researchgroupsacross7countries.Modificationofrewardmagnitudesmaybenecessarytoadjustfordifferencesincurrencyvaluations.
6. Isthetasksensitivetochangeandlackandlossoffunction?
i. Repeated-administrationshaveshownsensitivityofthetasktomanipulationsofdopamine(amphetamine)3andadenosine3.
7. Canthetask(oritsanalog)beusedinanimals?
i. Yes–thetaskwasmodeledafterwell-knowneffort-baseddecision-makingparadigmsinrodents1,15,16
8. Canthetaskbeusedacrossagegroups?
i. Some(unpublished)datahavebeenadministeredinchildren.
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9. Canthetaskbeusedwithmethodstointerrogatebraincircuitry(e.g.,fMRI,EEG,etc.)?
i. Yes–publisheddatahavelinkedthetaskoffMRI17,EEG4,18,anddopamine-receptorPETimaging4
10. Isthereconsensusonwhichmetric/scoreshouldbeconsideredtobeprimary?
i. Totalproportionofhardtaskchoicesii. Differenceinproportionofhardtaskchoicesforhighvs.lowprobabilitylevelsand/or
reward
11. Areadequatenormativedataavailableacrossage,gender,education,ethnicity,SES?
i. Thetaskhasbeenadministeredinover1,000individuals.Age,Sex,IQandSESnormsareintheprocessofbeingcompiled,andareexpectedtobepublishedinthewinterof2016.
12. Aretherelationshipsbetweentaskperformanceandneuralsignal(s)known?
i. Partially–functionalneuroimagingstudiesareinprogress
13. Aretherelationshipsbetweentaskperformanceandclinicalfeature(s)known?
i. Partially(seepoint#1)
14. Isthetaskfeasibleforadministrationacrosssites?
i. Yes
15. Canthetaskbeusedasastand-alonebehavioraltask?i. Yes–mostpublishedpapersusingthetaskhaveuseditasastand-alonetask
16. Whatworkisneededtogetthistaskreadyforuseinclinicaltrials?
i. Thetaskiscurrentlybeingusedinclinicaltrialsforschizophrenia.Preparationforotherpatientgroupsmayberequired.
17. Isthetaskcopyrighted?i. Thetaskiscopyrighted(EmoryUniversityandVanderbiltUniversity)andalicenseis
requiredfornon-academicuse(i.e.,industry).Thetaskismadefreelyavailableforacademicresearch.
References
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1. SalamoneJD,CousinsMS,McCulloughLD,CarrieroDL,BerkowitzRJ.Nucleusaccumbensdopaminereleaseincreasesduringinstrumentalleverpressingforfoodbutnotfreefoodconsumption.PharmacolBiochemBehav1994;49(1):25-31.
2. SalamoneJD,CorreaM.Themysteriousmotivationalfunctionsofmesolimbicdopamine.Neuron2012;76(3):470-485.
3. WardleMC,TreadwayMT,MayoLM,ZaldDH,deWitH.AmpingUpEffort:Effectsofd-AmphetamineonHumanEffort-BasedDecision-Making.JNeurosci2011;31(46):16597-16602.
4. TreadwayMT,BuckholtzJW,CowanRL,WoodwardND,LiR,AnsariMSetal.Dopaminergicmechanismsofindividualdifferencesinhumaneffort-baseddecision-making.JNeurosci2012;32(18):6170-6176.
5. TreadwayMT,BuckholtzJW,SchwartzmanAN,LambertWE,ZaldDH.Worththe'EEfRT'?Theeffortexpenditureforrewardstaskasanobjectivemeasureofmotivationandanhedonia.PLoSONE2009;4(8):e6598.
6. GeaneyJT,TreadwayMT,SmillieLD.TraitAnticipatoryPleasurePredictsEffortExpenditureforReward.PLoSONE2015;10(6):e0131357.
7. YangX-h,HuangJ,ZhuC-y,WangY-f,CheungEFC,ChanRCKetal.Motivationaldeficitsineffort-baseddecisionmakinginindividualswithsubsyndromaldepression,first-episodeandremitteddepressionpatients.PsychiatryRes2014;220(3):874-882.
8. TreadwayMT,BossallerNA,SheltonRC,ZaldDH.Effort-baseddecision-makinginmajordepressivedisorder:atranslationalmodelofmotivationalanhedonia.JAbnormPsychol2012;121(3):553.
9. BarchDM,TreadwayMT,SchoenN.Effort,anhedonia,andfunctioninschizophrenia:Reducedeffortallocationpredictsamotivationandfunctionalimpairment.JAbnormPsychol2014;123(2):387.
10. FervahaG,Graff-GuerreroA,ZakzanisKK,FoussiasG,AgidO,RemingtonG.Incentivemotivationdeficitsinschizophreniareflecteffortcomputationimpairmentsduringcost-benefitdecision-making.JPsychiatrRes2013;47(11):1590-1596.
11. McCarthyJM,TreadwayMT,BennettME,BlanchardJJ.Inefficienteffortallocationandnegativesymptomsinindividualswithschizophrenia.SchizophrRes2016.
12. ReddyLF,HoranWP,BarchDM,BuchananRW,DunayevichE,GoldJMetal.Effort-baseddecision-makingparadigmsforclinicaltrialsinschizophrenia:part1—psychometriccharacteristicsof5paradigms.SchizophrBull2015:sbv089.
13. TreadwayMT,PetermanJS,ZaldDH,ParkS.Impairedeffortallocationinpatientswithschizophrenia.SchizophrRes2015;161(2):382-385.
14. WardleMC,TreadwayMT,deWitH.Caffeineincreasespsychomotorperformanceontheeffortexpenditureforrewardstask.PharmacolBiochemBehav2012;102(4):526-531.
15. FlorescoSB,StOngeJR,Ghods-SharifiS,WinstanleyCA.Cortico-limbic-striatalcircuitssubservingdifferentformsofcost-benefitdecisionmaking.CognAffectBehavNeurosci2008;8(4):375-389.
16. WaltonME,BannermanDM,RushworthMF.Theroleofratmedialfrontalcortexineffort-baseddecisionmaking.JNeurosci2002;22(24):10996-11003.
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17. YangX-h,HuangJ,LanY,ZhuC-y,LiuX-q,WangY-fetal.Diminishedcaudateandsuperiortemporalgyrusresponsestoeffort-baseddecisionmakinginpatientswithfirst-episodemajordepressivedisorder.ProgNeuropsychopharmacolBiolPsychiatry2016;64:52-59.
18. HughesDM,YatesMJ,MortonEE,SmillieLD.Asymmetricfrontalcorticalactivitypredictseffortexpenditureforreward.SocCognAffectNeurosci2015;10(7):1015-1019.
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CognitiveSystemsFinalReport
CameronCarter,M.D.(chair),NealCohen,Ph.D.,JordanDeVylder,Ph.D.,DwightDickinson,Ph.D.,DamienFair,Ph.D.,MartaKutas,Ph.D.,SoheePark,Ph.D.,andLucinaUddin,Ph.D.
I.GeneralComments• InkeepingwiththecognitiveneuroscienceemphasisthatisatthefoundationofRDoC,
inourselectionoftasksandparadigmswehaveemphasizedconstructvalidityasthemostessentialoftheselectioncriteria.Intheinterestsoftimeandbecausetheylacksub-constructspecificity,wedidnotfocusonself-reportinstrumentsforthemeasurementofcognitivesystems.Inaddition,wheretheywererelevantwewereguidedbyexperiencesandfindingsfromtheCNTRICS/CNTRACSmeasurementdevelopmentinitiative.
• Wehavenotattemptedtoorthogonalizeconstructorsub-constructs.Thus,certaintasksandparadigmsmaybeappropriateformeasuringmultiplecognitivesub-constructs.
• AsisthecaseforotherRDoCsystemsanumberofthecognitivetasks/paradigmsthatseemmostappropriateforcertaincognitivesub-constructsarewell-establishedintheliteratureandconstruct-valid,buthavenotgonethroughrigorouspsychometrictestingandarenotstandardizedinaCNTRICS/CNTRACSsense.Assuchthesemeasureswereuniformlyratedashighonconstructvaliditybutlowonthepresenceofpsychometricdataorstandardizedmethodsofadministrationsuchasstimuluspresentationtimes,inter-trialintervals,numbersoftrialsperconditionetc.Assucheachparadigmthatwasconsideredisbetterdescribedas‘classes’oftasks/paradigmsthanasspecificmeasures.Insomecasesthereisonewidelyusedexemplaroftheclass–e.g.,thePosnerversionofspatialandnon-spatialcuingparadigms,andwenotethisintherelevantsection.Forothernewerapproaches(suchasrelationalinference,describedunderDeclarativeMemory)therearerelativelyfewexemplars.Ineithercase,theversionofthetaskdescribedinthereferencesforrecommendedparadigmscanbeconsideredagoodstartingpointforfurtherdevelopmentalworkdevotedtotaskoptimizationandpsychometriccharacterization.
• Itislikelytobenecessarytoparameterizetasksdifferentlyfordifferentpopulations.Thiscanbechallenging.Formanyparadigms,itwillbenecessarytoparameterizethetasksinawaythatpreservesconstructvalidityacrosspopulations,e.g.,childrenandadults.
• Oneadvantageofcognitiveneuroscienceparadigmsisthatmanyhavebeenusedinresearcharoundtheworld,andmanyusenon-verbalstimuli,reducingoreliminatinglinguisticandcross-culturaladaptationissues.
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• Theworkgroupdiscussedcertainpsychoticphenomena,particularlyhallucinationsanddelusions.Thesephenomenahavepresentedspecialchallengesandthefieldhasnotconvergedonanywell-specifiedmodeltodatethoughthereareinterestingtheoriesunderdevelopment(e.g.aberrantreinforcementlearning,defectiveBayesianprediction,impairedperformancemonitoring,alteredefferencecopyetc.).ThegroupfeltthatwhileimportantthesehavebeenchallengingtomodelwithinanRDoCcognitivesystemsframework,andgiventhecurrentstateofresearchandweoptedtonotspendtimeonthis.Reinforcementlearningmodels,whicharerelevant,arebeingaddressedunderPositiveValenceSystems.
• Amongthecognitivesystemsconstructsintheexistingmatrix,languagewaslesswellelaboratedthantheotherconstructs.Giventhespecializednatureofthefieldoflinguisticsaswellasevolvingconceptsthatinvokeinteractionsbetweencognitiveandlinguisticsystemswefeltthatitidentifyingconstructsandparadigmsfromthisdomainwouldbebestservedbyagroupwithmoreexpertiseinthearea.Anewreviewisnotedthatmayprovidesomeusefulcontextforthisdiscussion:Elvevag,Cohenetal.,AnexaminationofthelanguageconstructinNIMH'sresearchdomaincriteria:Timefor
reconceptualization!AmJMedGenetBNeuropsychiatrGenet.2016Mar10
• Traditionalcognitivetasks,suchasthoseoftenusedinneuropsychologicalbatteries,werediscussedgenerally,andspecificallyforsomeconstructs.Forthemostpart,thesewerejudgedtolackcognitiveconstructspecificityandwerenotrecommendedforRDoCpurposes.
II.OrganizationoftheDomain• Thereisconsiderablevariationintheelaborationanddisaggregationofcognitive
domainsandconstructsintheexistingRDoCMatrix.Someareinneedofupdatinginlightofcurrentcognitiveneuroscience.Inthiscontextwedidsuggestafurtherelaborationoftheconstructofattention.Specifically,weidentifiedthreeimportantsubdomains;controlledversusautomaticattention,capacitylimitationandinterferencecontrol,andsustainedattentionorvigilance.
• AsisthecaseincognitiveneurosciencetheorythereisconsiderableoverlapamongcertaindomainswithintheRDoCcognitivesystemsdomain,e.g.,betweenworkingmemory,attentionandcognitivecontrol.Similarly,thereisoverlapbetweenRDoCcognitivesystemsandotherRDoCdomains.Forexample,vigilanceisasub-constructofattentionandalsoanindexofarousal.Reinforcementlearningisanimportantformoflearningandmemorybutisbeingaddressedbypositivevalencesystems.Languagewasinitiallygroupedascognitivesystemsconstruct,butisalsocentraltosocialbehavior.
• PossibleadditionalRDoCdomains/constructswerediscussed.Theseincludedreasoning/inferenceandfuturesimulationwhichareemergingareasincognitiveneurosciencewithstrongclinicalrelevance.
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III.RecommendedTasksAllofthetasksbelowarerecommendedforinclusion.Asnotedaboveandforothernon-cognitivedomainswhileconstructvalidityisstrongforallofthesemeasuressomewillneedsubstantialdevelopmentintermsofoptimizationandpsychometricevaluation.
Attention
• Theparadigmslistedfortheattentiondomainare‘classes’ofparadigms,asdescribedabove.Theysharethecharacteristicsofwide-use,well-developedliterature,andhighconstructvalidity.Whileattentionhasbeenverywidelystudiedinbasiccognitiveneuroscienceforseveraldecades,withoneexception(theAttentionNetworksTask,seebelow),therearenostandardized,psychometricallyrefinedversionsofthesetasks.
Overt/CovertorBottom-upv.Topdown:
• Spatialandnon-spatialcuingtasks,includingPosnerversionsofthetasks1andtheAttentionNetworks(ANT)Task2.Limitedpsychometricdataareavailableforthelatter.
• Visualsearchparadigm3
CapacityandInterferenceControl:
• Attentionalblinkduringrapidserialvisualpresentation4• Dualtaskparadigms,includingversionsdevelopedbyPashler5
Vigilance:
• Varioustaskshave‘catch’trialsbuiltinthatpermitinvestigatorstoseparateattentionlapsesfromothereffectsofinterest(e.g.,changedetectionworkingmemorytasks,perceptualthresholdeffects)–attentionlapsesindexvigilance.6
• Thereisalsoaclassoftasksthathavebeendevelopedtoevaluateattentionlapsingor“mindwandering”duringavarietyoflaboratoryandeverydayactivities.Thesetasksincludeprobestoindexsubjectsawarenessoflapsingwhichhavebeenshowntocorrelatewithobjectivemeasuresoftaskperformanceaswellasneuralmeasuresoftaskrelatedbrainactivity7
Perception(Visual)
• Wefocusedourdiscussiononvisualperception–becauseneuralsubstratesdifferamongperceptualsystemsandbecausethescienceofvisualperceptionismorewell-developedthanthesciencerelatingtootherperceptualsystems
• Keyissuesforperceptiontasksandparadigmsincludecontrolforvisualacuity,lapsesofattention,andworkingmemoryimpairment.
• Forexample,CNTRACSworkhasshownthatremovingschizophreniasubjectswhofailattentionlapse‘catch’trialseliminatesgroupdifferencesonthecontrastcontrasttask(seebelow).Thisposesbothconstructvalidityandmeasurementconcerns.
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• SomeofthetasksrecommendedbelowhavebeenoptimizedandpsychometricallycharacterizedbyCNTRACS(Contrast-contrasttask,JOVI)orinthecaseofcontrastsensitivitybytheMARScompany.Theremainingshouldbeconsidered“classes”ofparadigmswiththereferencedversionsservingasgoodstartingpointsforfurtherdevelopmentintomorestandardizedandreliablemeasures.
Perceptualsensitivitythreshold:
• Contrastsensitivityparadigms,suchastheversionsdevelopedbyMars(http://www.marsperceptrix.com),isproprietary
• Aclassoftaskswithandasubstantialliteraturealsoexists,butwhichhaven’tbeenstandardizedorpsychometricallytested
Surroundsuppression:
• Thesearetasksindexingtheeffectivenessoflateralinhibitioninthevisualsystem.• Contrast-Contrasttask6
• Goodconstructvalidity• OptimizedandpsychometricallyrefinedforadultsubjectsthroughCNTRACS8• Thisoptimizedversionwhichincludescatchtrialstocontrolforattention
lapsingisavailablethroughtheCNTRACSwebsite(http://cntracs.ucdavis.edu/)
• Relationtoclinicalconditionsunclear–nogroupdifferencesinschizophreniaaftercontrollingforattentioninCNTRACSmulti-sitestudy6
Visualintegration:Tasksmeasuretheactiveintegrationofvisualfeaturesintopercepts.
• Jitteredorientationvisualintegrationtask(JOVI)9• Goodconstructvalidity• OptimizedandpsychometricallyrefinedforadultsubjectsthroughCNTRACS9• Thisoptimizedversionwhichincludescatchtrialsisavailablethroughthe
CNTRACSwebsite(http://cntracs.ucdavis.edu)• Sensitivetogroupdifferences9
DeclarativeMemory
• Althoughtherearemanymemorysystems,declarativememorywasidentifiedintheoriginalcognitivesystemsworkgroupmeetingasthebestmemorytargetforpsychopathologyresearchwithintheRDoCframework.Wemaintainedthatfocus.
Relationalmemory
• Theprocessesinvolvedinmemoryforstimuli/eventsandhowtheywereassociatedwithcoincidentcontext,stimuli,orevents.
• Relationalanditem-specificencodingtask(RISE)10• Goodconstructvalidityforbothrelationalanditemmemoryperformance• OptimizedandpsychometricallyrefinedforadultsubjectsthroughCNTRACS
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• ThisoptimizedversionisavailablethroughtheCNTRACSwebsite(http://cntracs.ucdavis.edu/)
• Goodevidenceofimpairmentinclinicalgroups(schizophrenia)10.• Evidenceofrelationshiptoeverydayfunctioninginschizophrenia11
Associativeinference
• Anemergingclassofparadigmsthathasgoodconstructvalidityfortheoperationofrelationalmemoryandtheabilitytoinfernewrelationshipsbetweenlearneditemsbasedupontheirrelationshipswithotheritemsacquiredduringlearning.
• Thisisadevelopingliteratureandanwithestablishedcanonicalparadigmbutthemeasuresarenotyetstandardizedandhaveunknownpsychometriccharacteristics12.Hencethisparadigmisrecommendedasaconstructvalidmeasurethat,likemanyothersinthecognitivedomain,willneedfurtherdevelopmentofanoptimizedversionthathasbeenpsychometricallycharacterized
Paired-associateslearning
• Variousmeasuresavailable(e.g.,fromWechslerMemoryScale)• Standardizedwithreasonablepsychometrics• TheWechslerversionisanoptionhoweverithasfeweritemsandlessprecisionthan
othertasks/paradigms.Experimentaltasksarefairlywidelyusedintheliteratureanddevelopingastandardizedtaskwouldbestraightforwardandisrecommended.
Patternseparation:
• Theabilitytodistinguishpreviouslypresenteditemsfromverysimilarfoils(i.e.,morechallengingthanmemorytasksinvolvingasimple‘oldv.new’distinction).AnewerandmorecomputationallyspecifiedaspectofDeclarativememorythathastheadvantageof:
• Moresensitivetoagingeffectsanddementiathanoldv.newparadigms• Knownrelationshipstomemorycircuitryinbrain
• MnemonicSimilarityTest,YassaandStarke13• Recommendedasconstructvalidbutpsychometricsnotknownandwillhave
tobeestablished,inordertohaveanoptimalstandardizedtask.
CognitiveControl
• Thisconstructincludesprocessesneededtomaintaingoaldirectedperformanceandovercomeprepotentandhabitualresponding
• Thereissubstantialsub-constructandtask/paradigmoverlapwithworkingmemorydomain
Responseinhibition:
• Paradigmslistedforthissub-constructare‘classes’ofparadigms,asdescribedinourgeneralcomments.Theysharethecharacteristicsofwide-use,well-developed
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literature,andhighconstructvalidity.Wearenotawareofstandardized,psychometricallyrefinedversionsofthesetasks.
• Go/No-gotasks14• Stopsignaltasks15
Goalmaintenance(orpreparatorycognitivecontrol):
• AXandDPXcontinuousperformancetests• Strongconstructvalidity16• Optimizedandpsychometricallyrefinedforadultsubjectsthrough
CNTRACSs8• OptimizedversionsareavailablethroughtheCNTRACSwebsite
(http://cntracs.ucdavis.edu/)• Evidenceofimpairmentinclinicalconditions17• Relatedtofunctionalmeasures
• Preparingtoovercomeprepotencytask(POP)• Goodconstructvalidityasagoalmaintenance/proactivecognitivecontrol
measure18o Psychometricshavenotbeencharacterizedo Agoodchoiceforusewithimpairedpopulations(psychoticdisorders,
autism)andchildrenduetosimpletaskstructure.19,20
Performancemonitoring(ordynamiccontrol):Posterrorandpost-conflictadjustments
• Eachofthesethreeclassesoftasks/paradigmscommonlyusedtomeasurethiscontructiswidely-usedwithwell-developedliterature,andreasonableconstructvalidity.Psychometricdevelopmentandoptimizationareneededexceptforflankercla21/postconflictadjustmentsmeasure.Versionsexistforuseinchildren22.OneexampleistheNIHToolboxFlankertask,whichhasbeenstandardizedforallagesandpsychometricallytested.Therearequestionsaboutwhetheritincludessufficientnumbersoftrialsbutitmightbepossibletocomputetrialtotrialandposterroradjustments(3minutesduration).
• Flankertaskversions• Simontaskversions• Strooptaskversions23
WorkingMemory
• Workingmemoryhasbeenextensivelystudiedinthecognitiveneuroscienceandindividualdifferencesliteratureandthemeasuresthathavebeenusedforthemostparthavenotbeenstandardizedorpsychometricallycharacterized.TheexceptionstothisaretheAX/DPXmeasureofactivemaintenanceandthechangedetectionmeasureforworkingmemorycapacitythathavebeendevelopedbyCNTRACS.
• Asnotedabove,thereissubstantialsub-constructandtask/paradigmoverlapwithcognitivecontroldomain
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Capacity:
• Changedetection• Variousversionsandwell-studiedparadigmwithgoodconstructvalidity24• Astandardized,psychometricallytestedversionisindevelopmentandwill
beavailablethroughCNTRACSinroughlyoneyear
Flexibleupdating:
• NBack25• Manyversionsandwell-studiedparadigmwithreasonableconstructvalidity
• Self-orderedpointing26• Widely-usedwithwell-developedliterature,andreasonableconstruct
validity.
ActiveMaintenance:
• Matchtosampletasks• Variousversionsandwell-studiedparadigmwithgoodconstructvalidity27• Widelyusedinanimalmodelsfromprimatestobirds
• Sternbergtasks• Variousversionsandwell-studiedparadigmwithgoodconstructvalidity28
• Changedetection(seeabove)24• AXandDPXcontinuousperformancetests(seeabove)
Interferencecontrol:
• Relatedtoactivemaintenance,butemphasizingtheextrademandsandeffortassociatedwithresistingdistractionorlapsingattention
• NBack(seeabove)• Sternbergtasks(seeabove)28
o Someversionsofthesetaskshaveinterferencebuiltin.
IV.Tasksthatarenotrecommended
ConstructAttention
• MismatchNegativitywasmentionedasafairlywell-developedauditoryperceptionparadigm,butitdoesnotyieldabehavioralperformanceindexanditwasnotconsideredfurtherforcurrentpurposes.Alsoweoptedtofocusonvisualattentionforthereasonsspecifiedabove.
ConstructRelationalMemory
• PairedAssociatedLearningformtheCANTABwasdiscussedbutnotrecommendedduetolowconstructvalidityforitemversusrelationallearningandbecauseitisproprietary.
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ConstructWorkingMemory,FlexibleUpdating
• Letternumbersequencingo Well-knownpaperandpenciltaskthathasbeenstandardizedandpsychometrically
refined(e.g.,fortheWAISIQbatteryo Lacksexperimentalrefinementbutmaybeusefultogetanapproximateindexof
thissub-constructthoughnotwithoutcontroversye.g.29
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SystemsforSocialProcessesFinalReport
JedElison,Ph.D.,WilliamHoran,Ph.D.,JamesMorris,Ph.D.LynnPaul,Ph.D.,KevinPelphrey,Ph.D.(chair)
I.GENERALCOMMENTSWeselectedasetofbehavioralperformance,self-reportandparadigmstoassayvarioussocialprocessesdescribedintheRDOCmatrix.Ourgoalwastoidentifythebest,currentlyavailable,tasks.Wealsosoughttoidentifyareaswhereadditionalresearchisneededinordertofurtherdeveloptasks.Themajorityoftasks,evenifconsideredthebestavailableoptions,areinneedofadditionalworktosupporttheiruseacrossRDoCprojects.Inparticular,allofthetasksweidentifiedneedadditionalrefinement(e.g.,psychometricproperties,norms)foruseacrosspediatric,adolescent,andadulthealthy/clinicalpopulations,aswellasthedevelopmentofnormativegrowthcurvesforthetypicaldevelopmentoftargetedneuralsystems.Onvirtuallyeveryparadigm,task,self-reportwerecommendmoreresearchtoestablishpsychometricproperties,norms,growthchartsoflongitudinaldevelopmentalchanges,developmentofage-appropriateparadigmsandapplicationtoclinicalgroups.
II.ORGANIZATIONOFTHEDOMAINWerecommendadditionalworkspecificallyonthefollowingissues/constructs/tasks:
• AffiliationConstruct–Thefieldneedsdevelopmentofmethodstoassessreciprocaldyadicinteractionofestablisheddyads(parent-child;spouses)anddyadicinteractionofanindividualandstranger.
• ConsiderRejectionSensitivityandSocialMotivationaskeysubconstructsunderAttachmentandAffiliationintheRDOCmatrix.
• TheconstructofSocialCommunicationInitiation(Faces)needsdevelopmentofbothmethodsofelicitingemotionsandmethodsformeasuringfacialexpression(thelatterisripefordevelopmentofnewtechnology).
• ForthebroaderconstructofSocialCommunication(i.e.notface-specific),thereisasignificantneedfordevelopmentoftechniques/instrumentsthatcapturethedimensionalityoffunctioningacrossthelifespanandpopulationsandinstrumentsthatoptimizeecologicalvalidity.
• TheconstructofUnderstandingMentalStatesneedsworkfocusedontaxonomyandtaskdevelopmentparticularlyathigherlevelsofcomplexity(inference,irony).
• Affective/SocialTouch–Studiesareneededtofurtherdevelopourunderstandingofthisimportantaspectofsocialcognition.
• Theover-representationofpsychodynamically-inspiredattachmentparadigms(e.g.strange-situation)wasconcerningbecauseofthegenerallackofsupportforthefoundationaltenetsofpsychodynamictheory.Thisistasksandparadigmsemergingfromthetheorychallenging,astheytendtolinkdirectlytoo,andreifythetheoreticalclaims.
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III.RECOMMENDEDTASKSAssessmentofMeasures:Weevaluatedaseriesofparadigmsundereachoftheconstructs,andratedaselectionofthemostpromisingofthesetasks.OurratingscanbefoundbelowinAppendixSSP-I.Aquestionmarkindicatesalackofknowledge/dataforthecriteria,andthusanopportunityforadditionalresearch.Ratingthetaskimpliesthatwearerecommendingthistaskasthecurrentbestoption(eventhoughsomearestillquitepooroptions).
A. AFFILIATIONANDATTACHMENT:NONE
RejectionSensitivity(newproposedsubconstructunderAffiliationandAttachment):
Cyberballisthestate-of-the-artparadigmforthemeasurementofRejectionSensitivity.Butitneedsdevelopmentinordertomakeitusefulasabehavioralmeasure.
• Recentmeta-analysis1provideextensiveinformationaboutthistask.• Thistaskhasbeenusedinarepeatedconfiguration(essentialforlongitudinal
studies)andfindingsindicatedgoodrepeatability2butthismaydifferbysubjectcohort.o Thereneedstobemoreworkontest-retestreliabilityacrosssubjectgroups
andstudiesofdevelopmentinchildrenandadolescents.o ThemostconsistentoutcomesinCyberballaremeasuredviafMRI,with
limiteddimensionalityofbehavioraloutcomeo Elementsofthetaskcanbestandardizedbutthusfar,thetasksarequite
variable.o Weneedworkcomparingbehavioraloutcomeparadigmsandestablishinga
standardizedbehavioralimplementationofCyberball.
SocialMotivation–Approach/Avoidance–(newproposedsubconstructsunderAttachmentandAffiliation):
WerecommendtheOne-ArmBanditTask3asameasureofsocialmotivation–i.e.,toapproachsocialrewardoravoidsocialpunishment/threat.Thisparadigmmeasureslearninginresponsesocialfeedback(happyvs.angryfacestimuli).
• Thistaskhasn’tbeenusedwidelyyetsoneedsmoreresearchtoestablishpsychometricproperties,norms,developmentofage-appropriateparadigmsandapplicationtoclinicalgroups.
WerecommendtheMultidimensionalScaleofPerceivedSocialSupport(MSPS)4Questionnaire
• TheMSPShasbeenusedwithvariouspopulations(4ethnicgroups)andthereliabilityofmeasurehasbeenreporteddowntoage35.Ithasgooddimensionalityandmeasuresmeasuresstate,butneedsworkontest-retestreliability.
B. SOCIALCOMMUNICATION
ReceptionofFacialCommunication
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• Facialemotion(staticfaces):TheER40-PennEmotionRecognitionTest6isrecommended.
• Jointattention:TheGazeCuingtask7isthecurrentgoldstandard.Thetaskiswellestablishedbutnotwellstandardized.Theeffectisclear,butthetaskneedsmoreworkonstandardizationandthedevelopmentofnorms.
ProductionofFacialCommunication:NONEarereadyfor“prime-time”.
Non-FacialCommunication(MergedPerceptionandInitiation)
• WerecommendchangingtheRDOCmatrixtomergeperceptionandinitiation.• Thisareaisripefordevelopmentusingtechnology.• WerecommendtheSocialResponsivenessScale8asaquestionnaire.Thisisa
psychometricallyrobustmeasureforvariousages.Ithasgooddimensionalityacrossthewholepopulation.Itmeasuresaconstructthatisnotstatic(e.g.weight).Itisnotabehavioralperformancemeasure,however.Insteaditisareportcompletedbyacloseother(e.g.,spouseorparent).
• WerecommendtheTASIT19formeasuringtheperceptionofemotionspresentedthroughmultiplemodalities:.
• Therewasextensivediscussionaboutthesubcategoriesanddifficultygroupingtopics:vocalparalinguistic(e.g.pace,prosody,pitch,volume);interpersonalfeatures(e.g.turn-taking,proxemics).Thisareaneedsextensivedevelopment;specificallyrelatedtoinstrumentsthatcapturedimensionalityoffunctioningacrossagerangeandpopulationsandinstrumentsthatoptimizeecologicalvalidity.
C. PERCEPTIONANDUNDERSTANDINGOFSELF
Self-Knowledge
• WerecommendtheSelf-ReferentialMemory10task.TasksofthiskindhavebeenusedmostlyinfMRI&ERPparadigms.However,theysufferasbehavioraltasksbecauseoftheabsenceofclearbehavioraldatafromtheseparadigms.
D. PERCEPTIONANDUNDERSTANDINGOFOTHERSAnimacyPerception
• Thecurrentgold-standardforthemeasurementofAnimacyPerceptionisPoint-LightDisplaysofBiologicalMotion11.Thisparadigmneedsworkonstandardizationoftasks,andcreationofnormativedata,includinggrowthcurvesofdevelopmentofbrainmechanismsfortheperceptionofbiologicalmotion.
• WealsonotedtheuseofAnimations(e.g.Castelligoal-directedversions12)aspromising,butinneedofstandardization.
ActionPerception
• WediscussedtheHowofWhy/HowTask13
(http://www.bobspunt.com/whyhowlocalizer),notingitneeddevelopmentacrossmanydomains,butrecommendingthistaskasthebestavailablecurrently.
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• Simpleimitationtaskshavebeenemployed,butthesearenormallyusedasabrainmeasurewithceilingofbehavioralperformance.
• Similarly,forActionPerception,especiallyintermsofactionstowardsgoals,weknowofextensiveneuroimagingwork,butintheabsenceofaclearbehavioraltask.
UnderstandingMentalStates
• Logical/PhysicalPerspectiveTaking(e.g.FalseBelief,HintingTask,StoriesfromEverydayLife).WerecommendtheHintingTask14asacurrentbestoption.
• Mental/EmotionalPerspectiveTaking(e.g.EmpathicAccuracy,FalseBelief,TASIT2&3,ReadingMindintheEyes15).WerecommendthereadingReadingtheMindin
theEyesTaskasacurrentbestoption.
IV.TASKSTHATREQUIREFURTHEREVALUATIONSelf-Knowledge
• WediscussedSelf-Relevantprocessing(e.g.Self-ReferentialMemory10).WenotedthesetaskshavebeenusedmostlyinfMRI&ERPparadigms.Assuch,theysufferasbehavioraltasksbecauseoftheabsenceofclearbehavioraldatafromtheseparadigms.
• WediscussedIdentificationofownemotionalstates(e.g.TAS-20).• WeconsideredRealityTesting(e.g.sourcememoryparadigms).• WediscussedthecomparisonofSelfandOtherratingsofsocially-relevantfunctions
(BRIEF,ABAS).
ProductionofFacialCommunication:NONE
• Spontaneousfacialemotiongeneration:Thereisnotastandardizedparadigmforelicitingfacialemotion(forexamples,see16,17).TherearevariousmethodsformeasurementsuchasFACS(http://www.paulekman.com/facs/orFACES(socrates.berkeley.edu/~akring/FACES%20manual.pdf),plusEMG.Weneeddevelopmentofstandardizedmethodsforelicitingemotionandsimplifiedsystemsformeasuringfacialexpression.
• Mimicry/imitationofemotionalexpression:Weneeddevelopmentofstandardizedmethodsforelicitingimitation/mimicryandsimplifiedsystemsformeasuringfacialexpression.
• Jointattention:ThereareseveralexcellentresearcherswhohaveemphasizedthisareainchildrenincludingPeterMundyandMichaelTomasello.Thisisaveryimportantconstructthatishasbeendevelopedforages9-24months,butitneedsdevelopmentandmeasurementtheforentirerelevantagerange,includingmodificationoftheconstructtoinclude,perhaps,jointintentions,intentionsharinginolderchildrenandevenadults.
• Wenotedthattheareaofmeta-cognitionofperformanceneedsdevelopment.
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V.TASKSTHATARENOTRECOMMENDEDWereviewedthetaskscurrentlysuggestedintheRDOCmatrix.Fromthisreview,werecommendeliminatingfromthematrixthe:1)separation-reunion(e.g.,StrangeSituation);2)StillFace;and3)FordCorollaryDischargeparadigms.Separation-reunionparadigmsarelimitedbyaninherentrelianceonaparticularsetoftheoreticalassumptions(i.e.,attachment-theory)thatarewidelydebated.TheStillFaceparadigmisveryspecifictoonedevelopmentalepochandhaslittlepredictiveutility.TheFordparadigmdoesnotutilizeabehavioraloutput,andisthusoflimiteduse.Thisrecommendationisnotmeanttoimplythatweendorsealltherestofthetaskslistedinthematrixinthesocialdomain—onlythatweidentifiedparticularlysignificantproblemswiththeoneswerecommendhereforremoval.
WediscussedbutexcludedfromfurtherconsiderationtheSocialNetworkIndex18.Ontheonehand,thisisn’tabehavioralperformancemeasure,makingitlesswellsuitedfortheRDOCapproach.However,thismeasureisassociatedwithamygdalavolume19.Wediscussedtheuseofthismeasuretoassessaffiliation,butdecidednottorecommendthistaskbecauseitisanindexofsocialoutcomesthatareinformedbymultipleprocesses.
References1. HartgerinkCHJ,vanBeestI,WichertsJM,WilliamsKD.TheOrdinalEffectsofOstracism:
AMeta-Analysisof120CyberballStudies.VanYperenNW,ed.PLOSONE.2015;10(5):e0127002.doi:10.1371/journal.pone.0127002.
2. BollingDZ,PitskelNB,DeenB,etal.Dissociablebrainmechanismsforprocessingsocialexclusionandruleviolation.NeuroImage.2011;54(3):2462-2471.doi:10.1016/j.neuroimage.2010.10.049.
3. LinA,AdolphsR,RangelA.Socialandmonetaryrewardlearningengageoverlappingneuralsubstrates.SocCognAffectNeurosci.2012;7(3):274-281.doi:10.1093/scan/nsr006.
4. ZimetGD,DahlemNW,ZimetSG,FarleyGK.Themultidimensionalscaleofperceivedsocialsupport.Journalofpersonalityassessment.1988;52(1):30-41.
5. BruwerB,EmsleyR,KiddM,LochnerC,SeedatS.PsychometricpropertiesoftheMultidimensionalScaleofPerceivedSocialSupportinyouth.ComprehensivePsychiatry.2008;49(2):195-201.doi:10.1016/j.comppsych.2007.09.002.
6. ErwinRJ,GurRC,GurRE,SkolnickB,Mawhinney-HeeM,SmailisJ.Facialemotiondiscrimination:I.Taskconstructionandbehavioralfindingsinnormalsubjects.PsychiatryResearch.1992;42(3):231-240.doi:10.1016/0165-1781(92)90115-J.
7. FriesenCK,KingstoneA.Theeyeshaveit!Reflexiveorientingistriggeredbynonpredictivegaze.PsychonomicBulletin&Review.1998;5(3):490-495.doi:10.3758/BF03208827.
8. ConstantinoJN,DavisSA,ToddRD,etal.ValidationofaBriefQuantitativeMeasureofAutisticTraits:ComparisonoftheSocialResponsivenessScalewiththeAutismDiagnosticInterview-Revised.JAutismDevDisord.2003;33(4):427-433.doi:10.1023/A:1025014929212.
9. McDonaldS,FlanaganS,RollinsJ,KinchJ.TASIT:ANewClinicalToolforAssessingSocialPerceptionAfterTraumaticBrainInjury.TheJournalofHeadTraumaRehabilitation.
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2003;18(3):219.10. KelleyWM,MacraeCN,WylandCL,CaglarS,InatiS,HeathertonTF.FindingtheSelf?An
Event-RelatedfMRIStudy.http://dxdoiorg/101162/08989290260138672.March2006.doi:10.1162/08989290260138672.
11. BjörnsdotterM,WangN,PelphreyK,KaiserMD.EvaluationofQuantifiedSocialPerceptionCircuitActivityasaNeurobiologicalMarkerofAutismSpectrumDisorder.JAMAPsychiatry.2016;73(6):614-621.doi:10.1001/jamapsychiatry.2016.0219.
12. CastelliF,FrithC,HappéF,FrithU.Autism,Aspergersyndromeandbrainmechanismsfortheattributionofmentalstatestoanimatedshapes.Brain.2002;125(8):1839-1849.doi:10.1093/brain/awf189.
13. SpuntRP,AdolphsR.ValidatingtheWhy/HowcontrastforfunctionalMRIstudiesofTheoryofMind.NeuroImage.2014;99:301-311.doi:10.1016/j.neuroimage.2014.05.023.
14. CorcoranR,FrithCD.Autobiographicalmemoryandtheoryofmind:Evidenceofarelationshipinschizophrenia.PsychologicalMedicine.2003;33(5):897-905.doi:10.1017/S0033291703007529.
15. VellanteM,Baron-CohenS,MelisM,etal.The“ReadingtheMindintheEyes”test:SystematicreviewofpsychometricpropertiesandavalidationstudyinItaly.CognitiveNeuropsychiatry.July2013.doi:10.1080/13546805.2012.721728.
16. GrossJJ,LevensonRW.Emotionelicitationusingfilms.Cognition&Emotion.January2008.doi:10.1080/02699939508408966.
17. LangPJ,BradleyMM,CuthbertBN.Internationalaffectivepicturesystem(IAPS):Affectiveratingsofpicturesandinstructionmanual.TechnicalreportA-8.2008.
18. CohenS,DoyleWJ,SkonerDP,RabinBS,GwaltneyJM.SocialTiesandSusceptibilitytotheCommonCold-Reply.JAMA.1997;278(15):1232-1232.doi:10.1001/jama.1997.03550150036020.
19. BickartKC,WrightCI,DautoffRJ,DickersonBC,BarrettLF.AmygdalaVolumeandSocialNetworkSizeinHumans.Natureneuroscience.2011;14(2):163.doi:10.1038/nn.2724.
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AppendixSSP-I:Ratingsforrecommendedtasksontaskcriteria
Criteria(Rateeachonascaleof1-5,with1=doesnotdoagoodjobofmeetingthecriterion;
5=doesanexcellentjobmeetingthecriterion
Construct
Task
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easure
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dataavailable?
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copyrighted?
AttachmentandAffiliation
1.Directbrainandbehaviormeasuresofrejectionsensitivity(Cyberball,ChatRoom)
2.SocialMotivation–Approach/Avoidance(e.g.,SocialIncentiveDelayTask;DotProbe/AttentionBias;One-Armed-BanditTaskandotherneuroeconomicstasks)
3.Selfreportofneedforaffiliation/rejectionsensitivity(MultidimensionalScaleofPerceived
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SocialSupport;AnhedoniaScale;RejectionSensitivityScale;AffiliationTendencyScale)
SocialCommunication
ReceptionofFacialCommunication
Jointattention,responding(gazecuing);
FacialEmotion(facescanpaths;ER40)
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Mimicry/Imitateemotionalexpression(FACScoding/EMG
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MultimodalSocialPragmatics(e.g.,vocal:pace,prosody,pitch,;turn-taking,distance,touch,gestures;BLERT;TASIT1;CASL-PL)
? ? ? ? ? ? ? ? ? ? ? ?
PerceptionandUnderstandingofSelf
Agency Illusionsofwill(rubberhand)
JoystickManipulation(decouplingmotorandsensoryfeedback)
Measureofsenseofcontrol
? ? ? ? ? ? ? ? ? ? ? ?
Self-Knowledge Self-ReferentialMemoryParadigm
Self-referentialeffect
BRIEF,ABAS–selfvs.otherratingofknowledgeofself
Identifyownemotionalstates
Realitymonitoring
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PerceptionandUnderstandingofOthers
Animacyperception
Pointlightdisplaysofbiologicalmotion
HeiderandSimmeltypefilms(goal-directed)
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ActionPerception
HowpartoftheHow/WhyTask(BobSpunt)
Imitation(fingertapping)
Contagion(yawning)
Actionobservation–goaldirectedactions
5 ? ? ? ? ? 5 5 5 ? ? 5
UnderstandingMentalStates
Logical/PhysicalPerspectivetaking(e.g.,HintingTask,FalseBelief,StoriesfromEverydayLife)
Mental/EmotionalPerspectiveTaking(e.g.,ReadingtheMindintheEyes,FalseBelief,EmpathicAccuracyParadigm,TASITparts2&3)
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ArousalandRegulatorySystemsFinalReport
TheodoreP.Beauchaine,RuthM.Benca,DavidBrent,AndrewKrystal,DaraManoach(chair),UmaVaidyanathan
ThisreportsummarizesthemeetingoftheArousalandRegulatorySystems(ARS)subgroupoftheNationalAdvisoryMentalHealthCouncilWorkgroup,whichwasestablishedbytheNationalInstituteofMentalHealth(NIMH)todevelop“alistofrecommendedtasksforeachRDoCconstructincludedintheRDoCmatrix”.TheARSsubgroupwaschargedwithdevelopingalistoftasksforthethreeconstructsintheArousalandRegulatorySystemsdomain:(1)arousal,(2)sleep-wakefulnesssand(3)circadianrhythms.Arousal/regulatorysystemsaredefinedintheRDoCmatrixas,“…responsibleforgeneratingactivationofneuralsystemsasappropriateforvariouscontexts,andprovidingappropriatehomeostaticregulationofsuchsystemsasenergybalanceandsleep(http://www.nimh.nih.gov/research-priorities/rdoc/constructs/arousal-and-regulatory-systems.shtml,June20th,2016).Sinceeffortful/activeformsofbehaviorregulationandemotionregulationarenotsubsumedwithinthisdefinition,theywerenotconsidered.Thus,theARSsubgroupworkeddirectlyfromconstructsalreadylistedintheRDoCmatrix(http://www.nimh.nih.gov/research-priorities/rdoc/constructs/rdoc-matrix.shtml),withoutrevisingoreditingthoseconstructs.
CONSTRUCT:AROUSAL
GENERALISSUES:ThetaskofrecommendingparadigmstoassessarousalpresentedtheARSsubgroupwithanumberofchallenges.Arousalisnotwell-definedintheRDoCmatrix,perhapsbecausethetermhashistoricalrootsthatcutacrossconstructsincludingorienting,vigilance,attention,motivation,traitandstateanxiety,stressresponding,andcoping,amongothers.Theseconstructsaresubservedbyawidearrayofneurobiologicalprocessesandfunctions,somecortical,somesubcortical,andsomeperipheral.Theseneurobiologicalprocessesandfunctionsarefacilitated/regulatedbymultiplemonoamineandneuroendocrinesystemsthataredistributedacrossdiversebrainregions.Evensinglemonoamineneurotransmitters(e.g.,dopamine)canbesubdividedintoseparatesystems(e.g.,mesocortical,tuberoinfundibular)thatareimplicatedindistinctarousalfunctions(attention,sleep).Giventhesecomplexities,andthetendencyofwhatwethinkofasdistinctpsychologicalfunctionstobewidelydistributedacrossneuralnetworks,itmaynotbepossibletodefinearousalas“…distinctfrommotivationandvalence…”,asoutlinedintheRDoCmatrix(http://www.nimh.nih.gov/research-priorities/rdoc/constructs/arousal.shtml).
Thisaboveparagraphillustrateswhymanycontemporarypsychophysiologistsavoidthetermarousalaltogether.Thatsaid,thereisconsiderablepsychophysiologicalresearchonconstructs,suchasthoselistedabove,thatcanbeconstruedasrelatedtoarousal.Historically,muchofthisworkwasconductedattheautonomicnervoussystem(ANS)level.Morerecently,electroencephalography(EEG)andfunctionalneuroimaging(e.g.,fMRI)havebeenused..Validself-reportmeasuresarelacking,butwouldbevaluabletodevelop.
MEASUREMENTISSUES:Mostofthemeasuresconsidereddidnothaveagreeduponstandardsforadministrationoranalysisandallwouldbenefitfromnormativedata.Allarescalabletovaryingdegrees.Alltaskscanbeaffectedbymultiplefactors,manyofwhichcrossintootherRDoCdomains(negativeandpositivevalence,cognition).Allrequiretightlycontrolledexperimentalconditionsforreliableandexternallyvalidassessment.
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AUTONOMICMEASURESOFAROUSAL
Mostautonomicmeasures,includingheartrate(HR),bloodpressure,andpupildiameter,areaffectedbyboththesympatheticandparasympatheticnervoussystems(SNS,PNS)1.Thisisproblematicwhenattemptingtoparserelativecontributionsofbottom-up,largelysubcortical,emotiongenerationsystemsfromtop-down,largelycortical,emotionregulationsystems(e.g.,prefrontal)2.Excitatorysympatheticefferenceisabetterindexofarousal,whereasinhibitoryparasympatheticefferenceisabetterindexofregulation3.HRcannotbeusedtocaptureeitherconstructbecauseitisrepresentedintwo-dimensionalspace,withSNSactivation(lowtohigh)ononeaxisandPNSactivation(lowtohigh)ontheotheraxis4.Thus,analmostunlimitednumberofSNSandPNScombinationscanresultinasingleHRvalue.Forthesereasonsandothers(bothfunctionalandanatomical),cardiacpre-ejectionperiod(PEP;assessedusingimpedancecardiography),anoninvasiveindexofSNSactivation(givenappropriatestimulusconditions),isabetterindexofarousal.PEPshortening,whichreflectsincreasedSNSactivation,isobservedreliablyduringstress-andemotion-inductiontasks,includingpublicspeakingandotherparadigmsinwhichone’sperformanceisevaluatedbyoutsideobservers5,6.
RECOMMENDEDMEASURE1:HEARTRATEVARIABILITY
Capturesbotharousalandregulation.Underappropriatestimulusconditions,highfrequencyheartratevariability(HRV,>.15Hzamongadults)assessesPNSefferencetotheheart7.AlthoughreductionsinHRVareobservedindisorderswherearousalisimplicatedinsymptomexpression(e.g.,panic,phobias,andotheranxietydisorders;non-suicidalself-injury;hostility),suchreductionsinHRVareinnowayspecificto‘disordersofarousal’.Infact,lowrestingHRVand/orexcessivereductionsinHRVduringemotionevocationarealsoobservedamongthosewithattentionproblems,autism,callousunemotionaltraits,conductdisorder,executivefunctiondifficulties,psychopathy,andschizophrenia2.StrongargumentshavebeenmadethatHRVisaperipheralindexofemotionregulatoryprocessesthatareaffectedbyprefrontalmechanisms.Thus,SNSmeasuresarelikelybetterindicesofarousal(particularlyduringsocialevaluation),whereasHRVislikelyabetterindexofregulation(particularlyduringemotionevocation).
• Reliability:SeveralstudieshaveevaluatedreliabilityofHRVmeasures8-12.Ingeneral,reliabilityisgoodforbothrestingstatemeasuresandtaskmeasures,whensuchtasksaretightlycontrolled(e.g.,welltrainedadministrator,nomovement,thesametaskusedacrossassessmentpoints),andwhenspectralanalysisisused.CleardevelopmentalincreasesinHRVareobserved,whichareobscuredwhenage-appropriaterespiratoryfrequenciesarenotusedwhenspectralanalyzingR-Rtimeseries.Perhapsunsurprisingly,reliabilityispoorwhendifferenttasksareusedtoevokeHRVreactivityatdifferenttimepoints.
• Norms:Althoughwell-establishednormsexistforrestingHRV,nosuchnormsexistforHRVreactivity,largelybecausetherearenoestablishedreactivitytasks13,14.Thisisproblematicgiventhatarousalislargelyaconstructofreactivity.However,reactivitydependsonanumberoffactorsthataredifficulttostandardize,includingageandothercomponentsoftheRDoCmatrix(seeabove),age,physicalfitness,individualdifferencesinexecutivefunction,andcardiovascularhealth,tonamebutafew.
• Otherpopulations:Therehasbeensomeworkdoneonpopulationsincludingchildren,adolescents,olderadults1,9,12,15-18.
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• Genetics,heritabilityandmoleculeshavealsobeenexplored19-22.• Braincircuitrycorrelates:AsrecentlyreviewedbyBeauchaineandThayer2,extensive
neuroimagingstudiesusingPET,SPECT,andMRIindicatethatHRVfallsundercontrolofaninterconnectedcorticalandsubcorticalnetwork,includingefferentpathwaysfromthemedialprefrontalcortextothePNS.Throughthisnetwork,theprefrontalcortexprovidestop-downinhibitorycontroloversubcorticalandbrainstemsystemsthatregulateautonomicfunction23-25.AlteredfunctionofthisPFCnetworkisobservedacrossawiderangeofpsychopathologies26,27.
• Useinclinicaltrials(yogaRCTs,openCBTtrials,emotionalregulationtraining)28-32.Clinicaltrialsconductedtodateamongchildren,adolescents,andadultsindicatethatbothrestingstateHRVandHRVreactivityimproveinresponsetoclinicalinterventionsforseveralformsofpsychopathology.Thesechangescorrelatewithimprovedemotionregulationcapabilities.Anumberofadditionalclinicaltrialsareunderway.
• Clinicalcorrelates(depression,bipolar,schizophrenia)17,33,34.ClinicalcorrelatesoflowrestingstateHRVandexcessiveHRVreactivity(parasympatheticwithdrawal)arewide-rangingandcorrespondwithdifficultieswithemotionregulation.Allofthefollowingpsychiatricdisorders/clinicalsyndromesarecharacterizedbylowrestingstateHRVand/orexcessiveHRVreactivity(forareviewseeBeauchaine&Thayer,2015):anxiety,attentionproblems,autism,callousness,conductdisorder,depression,non-suicidalself-injury,panicdisorder,phobias,traithostility,psychopathy,schizophrenia.
RECOMMENDEDMEASURE2:ElectrodermalResponding
Description:Electrodermalresponding(EDR),alsoknownasgalvanicskinresponseorskinconductance,isagoodperipheralbiomarkeroflowarousalstates/traits,butnotasgoodatdemarcatinghigharousalstates/traits.Ithasbeenusedinstudiesofemotionandcognitionsincetheearly1900sandisthoughttoindexperceivedstimulussignificance35.Itisgenerallymeasuredbyindexingchangesinconductancethatoccurinsweatglandsintheskinafterpassingaweakelectricalcurrentthroughelectrodesplacedonthefingertips.Itdoesnotdifferentiatebetweenaffectivestates,butismoredependentonthearousalvalueofstimulus.Ithasbothtonicandphasiccomponents.Phasiccomponentsaremeasuredasthechangeinconductanceuponpresentationofastimulus,whiletonicresponsesincludeskinconductancelevelandskinconductancelevel(seeBoucsein,201236foracomprehensivereview).Someresearchhasshownthatitcovarieswithamygdalaactivationtoexternalstimuli37.
Measurementissues:EDRshowshighreliability(see38forareview)andbiometricheritability39.However,aswithmanybiomarkers,linkstocandidategeneshaveprovedtenuouswithinitialfindingsnotholdingupinlargersamples.39EDRiseasytomeasureandwearabledevicessuchasEmpaticaareavailablebutareonlynowstartingtobeincorporatedintolargerlab-basedstudies.Aswithotherpsychophysiologicalmeasures,stimulusconditionsareimportantwhenevaluatingwhetherEDRmarksarousal.EDRcovarieswithamygdalaactivationtoexternalstimuliinwell-controlledexperiments.Non-specificfluctuationsintheEDRsignalmaybemoresensitivethanotherindices(e.g.,amplitude,risetime,recoverytime,etc.).Informationonrecordingstandardsandresponserangesisavailable35,40.
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Clinicalrelevance:DecreasedEDRhasbeenassociatedwithexternalizingdisorderssuchasantisocialbehaviorandalcoholabuse/dependenceconcurrentlyandpredictively41-47.Studiesofschizophreniaaredividedwithabouthalfshowingnoresponsetostimuliduringhabituationparadigms35,48.PTSDisassociatedwithincreasedelectrodermalresponding49,50.
RECOMMENDEDMEASURE3:Pupillometry
Pupillometryreferstothemeasurementofpupildiameter,includingconstrictionanddilation.Thisisaccomplishedusingvideorecordingandeye-tracking.Pupildilationcorrelateswithactivationofnoradrenergicfibersoriginatinginthelocuscoeruleus,whichsupportsuseofpupillometryasanindexofsympatheticnervoussystem(SNS)functionandarousal51,52.However,pupildiameterisalsodeterminedbyPNSinnervation.ItthereforesuffersfromthesameinterpretabilityproblemsasHR(seeabove).Furthermore,pupildilationisassociatedwithaspectsofemotionandcognition,andvariesasafunctionofemotionalsaliency53,taskdifficulty54,andattentiondeployment55.Thus,changesinpupildiameterarenotspecifictoarousal.Undersomecircumstances,pupildilationmaymoreaccuratelytracktemporalaspectsofattentionthanimagingmethodssuchasEEGandfMRI56,55.Althoughpupilsizechangesreflexivelydependingonambientlightconditions,pupillaryresponsesarealsoevokedbymechanismsunrelatedtovisualperception,whichmayormaynotberecognizedconsciously57.
• -Reliability:Alimitednumberofstudieshaveassessedreliabilityofpupillometry.However,existingstudiessuggestgoodtoexcellenttest-retestreliabilityforchangesinpupildiameter,dependingonthetaskusedandthepopulationbeingstudied58.
• -Useinclinicaltrials:Dataonchangesinpupillaryrespondingfollowingtreatmentforpsychopathologyaresparse.However,remissionfollowingcognitivetherapyfordepressionisassociatedwithlowsustainedpupillaryresponsestonegativewords59.
• -Clinicalcorrelates:Pupillometryhasbeenusedmostextensivelyamongchildren,adolescents,andadultswithautismspectrumdisorder.Whileviewingothers’faces,thosewithautismshowpupillaryconstriction,incontrasttotypicaldilatoryresponsesexhibitedbymental-ageandchronological-agematchedcontrols60.Martineauetal.61wereabletodifferentiatechildrenwithautismfrommental-andchronological-agematchedcontrolswith72%accuracybasedonreductionsinpupilsizewhenviewingneutralfaces,virtualfaces,andobjects.Pupildilationmaymarkmoregeneraltendenciestowardanxietyanddepression,atleastincertaincontexts62.Reducedpupildilationtonegativewordsisassociatedwithdepressionseverityandnegativeaffectivity,andwithlowlevelsofpositiveaffectivity63.
RECOMMENDEDMEASURE4:CARDIACPRE-EJECTIONPERIOD
Althoughnotdiscussedatthemeetingbecauseacommitteememberwithexpertisewasnotinattendance,cardiacpre-ejectionperiod(PEP)shouldbeincludedinanydiscussionofputativeautonomicindicesofarousal.PEPisdefinedbythetimeelapsed(ms)between(1)onsetofleftventriculardepolarizationand(2)ejectionofbloodintotheaorta64(seeSherwoodetal.,1990).PharmacologyblockadestudiesindicatethatPEPchangesinresponsetointernalandexternalstimuliaremediatedfullybybeta-adrenergic(SNS)mechanisms65.Wellcontrolledexperiments
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demonstratePEPshorteningduringheightenedarousalstates,includingthoseinducedbyincentiveresponding,threat,andpsychologicalstress66,67.UnlikeHRVhowever,whichchangesduringtheseconditionsandmanyothers(seeabove),PEPrespondingismuchmorespecific68.
• -Reliability:CardiacPEPdemonstratesadequatetoexcellentinternalconsistencyandtest-retestreliability.Cronbach’salphasduringdifficulttaskswithsocialevaluativecomponents—whichelicitconsiderablearousal—areexcellent69.Furthermore,stabilityofPEPrespondingisobservedacrossintervalsaslongasadecade70.
• -Norms:AsreviewedbyZisnerandBeauchaine1,restingPEPincreasesmonotonicallyasafunctionofagethroughearlyadulthood,afterwhichage-relatedchangesarenegligible71.DevelopmentalnormsforPEPreactivityaremoredifficulttoestablish,sincedifferentlabsusedifferentstimulitoevokePEPresponses.However,researchusingrewardtasksinparticularshowsnoconsistentdifferencesacrosspreschool,middlechildhood,adolescence,andearlyadulthood68,72-74.Incontrast,QuigleyandStifter75reportedgreaterPEPreactivityamongyoungadultsthanamongpreschoolersinresponsetoaseriesofreactiontime,emotionevocation,andinterviewtasks.Thus,consistentwithrecommendationsthroughoutthisreport,stimulusconditionsneedtobeconsideredcarefullywheninterpretingautonomicresponding,andinevaluatingwhetherautonomicresponsesrepresentchangesinarousal(seeabove).
• -Genetics,heritability,molecules:RestingPEP,ambulatoryrecordingsofPEPthroughouttheday,andPEPreactivitytostressaremoderatelytohighlyheritableinadolescenceandmiddleage76,77.FewmoleculargeneticsstudiesspecificallyofPEP/PEPreactivityhavebeenconducted.However,sincePEPchangeiseffectedthroughtheSNSviabeta-adrenergicmechanisms,candidatesincludetheb1-andb2-adrenergicreceptorgenes(ADRB1,ADRB2)78,andothergenesthataffectSNS-linkedcardiovascularreactivity.
• -Braincircuitrycorrelates.SinceSNS-mediatedincreasesincardiacoutputservetofacilitatebehavioralmobilizationtomultiplearousalstates,includingincentiveresponding,threat,andstress,nosingleneuralnetworkisresponsibleforevokingPEPresponses.Duringincentivetasksinparticular,PEPshorteninglikelyoriginatesindopaminergicreactivitywithinthestriatum,whichinitiatesbrainstemrespondingtomobilizeacardiacresponse3,79.Duringconditionsofthreatandstress,PEPrespondingislikelyinitiatedbyother,wellcharacterizedneuralnetworks(e.g.,SAM).
• -Useinclinicaltrials:Todate,PEPhasnotbeenevaluatedinmanyclinicaltrials.However,inarecentRCTofabehavioralinterventionforearly-onsetconductproblems,Beauchaineetal.28(2013)foundmaineffectsofPEPactivityandreactivityontreatmentoutcomes.Althoughsample-wideimprovementsinbehaviorwereobservedatpost-treatment,thosewhoexhibitedlengthenedcardiacPEPatrestandreducedPEPreactivitytoincentivesscoredhigheronmeasuresofconductproblemsandaggressionbothbeforeandaftertreatment.Thisisconsistentwithalowarousalinterpretationofconductproblemsandtreatmentresponse.Moreover,crosssectionalresearchcomparingPEPreactivitytostressamongcurrentlydepressedversusremittedpatientsindicatesbluntedPEPreactivityonlyinthosewhoarecurrentlydepressed80.Thus,PEPreactivitymaybeastatedependentmarkerofclinicaldepression.
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• -Clinicalcorrelates:Comparedwithcontrols,maleswithADHD,oppositionaldefiantdisorder,conductdisorder,andantisocialpersonalitytraitsexhibiteitherdiminishedPEPreactivitytomonetaryincentives,ornoPEPreactivityatall3.Similarfindingsapplytodepressedindividuals80.PEPnon-reactivitymaythereforemarkattenuatedmesolimbicreactivitytorewardinbothexternalizingbehavioranddepression.DiminishedPEPreactivitytoincentivesalsoprovidesprospectivepredictionofsubstanceuseinitiationandescalationamongmiddle-schoolers81.
Promisingmeasuresrequiringfurtherdevelopment
• ERPsduringsleep(e.g.,oddballparadigm)82• EEGbeta/gamma/thetaactivityduringsleepandwake83
Consideredbutnotrecommended
• HungerVisualAnalogueScale(insufficientdataonproperties)• Heartrate(seeabove)• Interoception(notaprimarymeasureofarousal)• CO2inhalation(usedtotriggeracutefear;negativevalencemeasure)• Startle(moreameasureofreactivitytonegativestimuli)• Bloodpressure(regulationtoocomplex)• Auditorysteadystateresponse(ASSR)measureofgammaband(ReferredtotheCognition
Group)• TrierSocialStressTest,FearFaces,IAPSpictures(Thesestimulievokearousalbutarenot
arousalmeasures)• Cortisolandserum/urinenorepinephrinelevels(insufficientpsychometricvalidity)
COGNITIVEMEASUREOFAROUSAL
RECOMMENDEDMEASURE4:PsychomotorVigilanceTask(PVT)
ThePVTrequiresparticipantstopressabuttonassoonasalightappearsonascreenatrandomintervals.RTandthenumbermissedbuttonpressesarethedependentmeasures.ThePVTrequiressustainedattentionandisthoughttoreflectalertness.Poorperformanceisassociatedwithsleepdeficit84.Performanceisalsoinfluencedbymotivationandcircadianfactors.AdvantagestothePVTarethatithasbeenwellstudied,hassimplemetrics,isbrief,freefromlearningeffectsandeasilyscored.Theanimalversionthathasbeenusedtodetecttheeffectsofsleepdeprivation85.Performancedependsonthebasalforebrain86andcanbedisruptedwithadenosineinfusionproducingbehavioraldeficitsresemblingsleepdeprivation87.
CONSTRUCT:SLEEP-WAKEFULNESS
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Polysomnography(PSG):Thefirstfourrecommendedmeasuresdependonpolysomnography,thesleepEEG.GeneralissueswithPSGincludescalabilitygiventheexpenseandtimerequiredforsleepstudies.Itremainstobeestablishedunderwhatconditionsanaporhomesleeprecordingscansubstitutefornocturnalsleepinthelab.Scoringandartifactrejectioncanbelaborious,butautomaticmethodsexistandarebeingdeveloped.Scoringandmeasurementofsleeparchitectureandqualityarehighlystandardized.Aminimumoftwosleepsessionsisrecommendedasthefirstsessionisgenerallyconsideredanadaptationnight(ornap)thatacclimatestheparticipanttothesleeplabandrecording.
RECOMMENDEDMEASURES1:Latencytopersistentsleep(LPS),Waketimeaftersleeponset(WASO),TotalSleepTime(TST)88-90
• Theseareallstandardwell-establishedmeasures.• recommendedtwonightminimum
RECOMMENDEDMEASURE2:SleepSpindles(87,96Rechtschaffen&Kales1968;Iberetal.,2007)
Description:SleepspindlesareadefiningoscillationofStage2nonrapideyemovementsleep(N2)seenonPSGas12-15Hzoscillationslasting1to2secondsinawaxingwaningenvelope.SpindlesarealsoseeninN3,buthavedifferentcharacteristicsandfunctionalcorrelates.Themostcommonmetricsaresleepspindlenumberanddensity.Themorphologicalcharacteristicsofsleepspindlesarealsooftencharacterizedincludingpeakamplitude,sigmapower,durationandfrequency.
Measurementissues:Thereareseveralpubliclyavailableautomatedmethodstodetectspindlesthathavebeenvalidatedagainsthandscoringbyexperts.Butexpertsdonothaveperfectinter-raterreliability91andwhileinternallyconsistent,differentmethodsgiverisetodifferentestimates.Sigmapower(12-15Hz),whichisthespindlefrequency,isoftenusedasaproxyforspindleactivity,butcorrelatesonlymoderatelywithhandorautomaticallydetectedspindles.Spindleshavebeendividedintoslowandfastfrequencyevents,butdefinitionsdiffer.Somepapershavedefinedfastandslowspindlesascovering13.5-15Hzand12-13.5Hzbands,respectively,whileothershaveidentifiedalowerbandofspindlesfrom9-12Hz.Fastandslowspindleshavedifferentscalptopographies,relationswithotherNREMsleeposcillationsandrelationswithwakingcognition,includingsleep-dependentmemoryconsolidation.Spindleschangeoverthelifespan92.Normativedataissoontobeavailable.
Clinicalrelevance:spindleactivityishighlyheritableandisrelatedtothefunctioningofgenesthatconferincreasedriskforschizophrenia93,94andotherneurodevelopmentaldisordersincludingautism95.Spindlegenerationdependsonawell-definedphysiologyandcircuitryinvolvingthethalamicreticularnucleusandthalamocorticalcircuitrythatisimplicatedinpsychopathology.Sleepspindlesarerelevanttocognitionandcorrelatewithsleepdependentmemoryconsolidation,IQandmeasuresoflearningpotentialinhealth96andpsychopathology97,98.Theycanbeexperimentallymanipulatedinbothhumansandanimalsusingpharmacologicalandneurostimulationtechniquestoimprovesleep-dependentmemoryconsolidation99,100.
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RECOMMENDEDMEASURE3:NON-RAPIDEYEMOVEMENTSLEEP(NREM)EEGSlowwaveactivity:Ameasureofsleephomeostasis(RateofDeclineinNREMEEGDeltaPoweracrossnight,NREMEEGAverageDeltaPower)88,101-115
Overview:Sleephomeostasisreferstotheincreaseinpropensitytosleepthatoccursinproportiontothedurationofpriorwakefulness.Theintensityofthepropensitytosleepatanygivenpointisreferredtoasthedegreeof“homeostaticsleepdrive”.ThereisacompellingbodyofliteratureinhumansandanimalsindicatingthatthedynamicsofEEGpowerintheDeltafrequencyband(typically0.5-4Hz)duringNREMsleepreflectthedegreeofhomeostaticsleepdrivethathasbuiltupatthetimeofsleeponsetandthedissipationofthisdrivethatoccurswithsleep.ThesestudiesdemonstratethatNREMEEGDeltaPowerintheearlypartofthenightandtherateofdeclineinNREMEEGDeltapoweroverthenightincreaseproportionallywiththedurationofpriorwakingandaredecreasedbymanipulationsthatdecreasehomeostaticsleepdrivesuchasextendingsleepandnapping.
Measurementissues:StudiesestablishingtherelationshipbetweenNREMEEGDeltaPowerdynamicsandhomeostaticsleepdrivehaveemployedanumberofstandardmethods.TheseincludetheuseofstandardmethodsforcomputingEEGDeltaPoweremployingtheFastFourierTransform(FFT)andidentifyingNREMsleepusingstandardsleepstagingcriteria88,101.However,studiesincludingNREMEEGDeltaPowerdynamicshavevariedinanumberofkeyaspectsofmethodology,whichremainunstandardized.TheseincludethenumberandlocationofscalpEEGelectrodesutilizedinestimatingNREMEEGDeltaPower,themethodsforidentifyingandremovingdatacontaminatedbyartifact,andtherangeoffrequencieswhichdefinetheDeltafrequencyband.
RECOMMENDEDMEASURE4:MultipleSleepLatencyTest(MSLT):AMeasureofDaytimeSleepiness
Overview:TheMultipleSleepLatencyTest(MSLT)isastandardizedlaboratoryassessmentofthedegreeofdaytimesleepiness.Itismeasuredasthepropensitytofallasleepwhenpresentedwithanopportunityinanenvironmentconducivetosleep.Subjectsaregiven4-5opportunitiestonapinaquiet,darkroomspreadacrosstheday.Foreachnapopportunity,thetimetosleeponsetisdeterminedfromPSGusingstandardscoringcriteria88.Theaveragetimetosleeponsetisthemeasureofsleeppropensity.BecausethetestrequiresPSGmonitoringinthelaboratorythenightbeforetesting,subjectsmustspendanightandasubsequentwholedayinthelaboratory.Althoughmethodshavevaried,astandardizedprotocolfortheMSLThasbeenproposedandwidelyadopted116.
Measurementissues:TheMSLThasgoodfacevalidityasameasureofsleepinessandithasbeenestablishedtohavegoodtest/retestreliability.Convergentvalidityhasbeenestablishedinthatitreflectstheeffectsofsleepdeprivationandtheeffectsofsedatingdrugs.Normativedatahavealsobeenestablished117.Itsmainlimitationsintermsofmeasurementissuesarethattherearefloorandceilingeffectsthataffectapplicationandthatithassignificantinter-individualvariabilitysuchthatitisinconsistentindistinguishinghealthycontrolswithoutsleepinesscomplaintsfromindividualswithdisordersofexcessivesleepiness.Assuch,itisabettermeasureofwithin-subjectchangeinsleepinessthananabsolutesleepinessmeasure.
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RECOMMENDEDMEASURE5:Insomniaseverityindex(ISI)
Thisistheonlyself-reportmeasurethatwerecommend.Bettervalidatedself-reportmeasuresofsleepandsleepinessareneededsincewidelyusedmeasureshavepoorpsychometrics(e.g.,Sleeplogs/diariesarenotstandardizedorvalidated).TheISIislimitedtoinsomniaassessment,itisnotageneralsleep-wakemeasure118.
RECOMMENDEDMEASURE6:Fingertappingmotorsequencetask(MST)
Description:TheMSTisameasureofsleep-dependentdaytimefunction119.Itassessestherestorativeandtransformativepropertiesofsleeponcognitionmeasuredduringwake.Itisthemostwell-validatedmeasureofsleep-dependentmemoryconsolidation.TheMSTrequiresparticipantstorepeatedlytypea5-digitsequence(e.g.,4-1-3-2-4)onakeyboardwiththelefthand,“asquicklyandaccuratelyaspossible”fortwelve30strialsseparatedby30srestperiods.Participantstrainbeforesleepandaretestedonanadditional12trialsaftersleep.Theprimaryoutcomemeasureisovernightimprovementcalculatedasthepercentincreaseincorrectlytypedsequencesfromthelastthreetrainingtrialstothefirstthreetesttrials120.TheMSTtapsprocedurallearningandmemory.OvernightimprovementontheMSTcorrelateswithsleepspindledensity121-123and,inonestudy,changesinsigmaactivityinthesupplementarymotorareaasmeasuredbyMEG124.Patientswithschizophreniaanddepressiongenerallyperformaswellascontrolsintheinitialsessionintermsoftheamountandproportionoflearning,butshowaspecificdeficitinovernightimprovement97,98,125,thatinschizophrenia,correlateswithasleepspindledeficit126.Overnightimprovementhasbeenlinkedtoprefrontalhippocampalconnectivityduringlearning127.
Measurementissues:Administrationiscomputerized.Performancemaybeaffectedbykeyboardingexperience.Ideally,thetaskisadministeredonconsecutivedays.Measurementmaybehighlyvariableinsomeparticipantsandinvestigatorshavedifferentmethodsofeliminatingoutlyingresponses.
Consideredbutnotselected:
• Word-pairassociateslearning:Awell-validatedmeasureofsleep-dependentdeclarativememoryconsolidation.Apotentialissueinpsychopathologyresearchisthatparticipantsoftenhavedeclarativeencodingdeficitsthatrenderitdifficulttoattributepoorrecalltosleep128.
• MaintenanceofWakefulnessTest(MWT)(probesabilitytoremainawake,butinsufficientpsychometricdata/norms)
• Actigraphy(notareliablemeasureofsleep,includedundercircadianrhythms)
CONSTRUCT:CIRCADIANRHYTHMS
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Generalconcerns:Mostmeasuresofcircadianrhythmscanbeinfluencedbycircadianentrainingfactorssuchaslight,activity,feedingandtimingofsleep.Forcircadianoutputsthatarealsoinfluencedbyhomeostaticsleepfactors,suchascognitiveperformance,durationofwakefulnesscanalsoeffectmeasurement.Asaresult,circadianrhythmsinhumanshaveoftenbeenmeasuredunderoneofseveralprotocols,includingtimeisolation(subjectsplacedinanenvironmentisolatedfromtimecues,nolongercommonlyused),forceddesynchrony(subjectsforcedtofollowrest-activityschedulesthataretooshortortoolongtopermitentrainment),andconstantroutine(subjectsremainawakeandsemi-recumbentindimlight,withnourishmentprovidedatauniformlevelthroughout)129-131.Corebodytemperaturerhythmmeasurement,whichusedtobeconsideredthegoldstandard,isnolongerfrequentlyusedduetoitsinvasiveness(subjectsneedtowearrectaltemperatureprobesorswallowthermometercapsules),andmeasurementofmelatoninsecretionpatternshasbecomeoneofthemostwidelyusedmarkersatthepresenttime.
RECOMMENDEDMEASURE1:DimLightMelatoninOnset(DLMO)132
Description:Melatoninissynthesizedbythepinealglandanditssecretionisregulatedbythecircadianrhythm(releaseoccursatnight),butsuppressedinthepresenceoflight.Itisthemostfrequentlyusedmarkerofcircadianrhythmsinceitcanbemeasuredinsaliva,bloodandurine.
Measurementissues:Althoughafrequentlyusedmeasure,thelackofconsistencyacrossstudiesinsamplingandmeasuringmelatoninhasmadecomparisonsofresultsdifficult.AworkgroupoftheAssociatedProfessionalSleepSocietieshasmaderecommendationsregardingthecollectionandanalysisofmelatonin133.Theysuggestedthaturinecollectionevery2-8hoursover24-48hoursmaybemostpracticalinthehomesetting,althoughlessprecisethanotherapproaches.Melatonincanalsobemeasuredfromsalivasamplescollectedathomeorinaresearchorclinicalsettingevery30-60minunderdimlightingconditions(<30lux),butthisrequireswakingthesubjectacrossthenight.Frequentbloodsamplingformelatoninthroughanindwellingcatheterpotentiallyallowsthepatienttosleep,butisthemostinvasivetechniqueandmustbeperformedinaresearchorclinicalsetting.Melatoninlevelsarehigherinplasmathaninsalivaorurine,makingplasmasamplingthemostsensitivemethodtoestimatecircadianphase,amplitudeanddurationofsecretion.Themostcommonlyusedphasemarkerisdim-lightmelatoninonset(DMLO),usuallyobtainedbymeasuringmelatoninevery20-30minforseveralhourspriortothenormalsleepperiod,ordim-lightmelatoninoffset(DLMOff),thetimewhenmelatoninlevelsdropattheendofthenight.ThereisstilllackofconsistencyastothethresholdsormethodologiesusedtocalculateDLMOorDLMOff,however.Otherissuesincludetheeffectsoflightexposurepriortoandduringsampling,andthefactthatmelatoninlevelsarelowinsomeindividuals.
RECOMMENDEDMEASURE2:Longitudinalactigraphy(acrophase,mesor,amplitude)134,135
Description:Actigraphyinvolveswearingawristwatch-likemonitorthatcontainsamovementdetector(accelerometer)andcansampleandstoremovementdatainaslittleas1secondbinsoverweeks.Wristactigraphyhasfrequentlybeenusedtoestimatesleep,basedonthefactthatlittlemovementoccursduringsleep.Italsomeasuresactivitypatternsoverthe24-hourday,
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whichareusedtoestimatecircadianparameterssuchacrophase(timeofpeakactivity),mesor(averageactivity),phaseofthecircadianrhythmandregularityofrest-activitypatterns.Aminimumof1weekofdata,andpreferably2weeks,shouldbecollectedforassessment,andthemonitoristypicallywornonthenon-dominantwrist.Inclinicalsituationsitisusedtoestimatesleeppatternsandintheevaluationofpatientswithcircadianrhythmdisorders.Ithasalsobeenusedsuccessfullytoevaluaterest-activitypatternsandcircadianrhythmsinpatientswithpsychiatricdisorders.
Measurementissues:Whilerecommendedasameasureofcircadianrhythms,itisnotrecommendedasameasureofsleep.Actigraphycannotdistinguishsleepfromquietwakefulnessand,inonestudy,wasshowntobeanunreliablemeasureofsleepduration(basedonPSG)inschizophreniapatientswhotendedtospendlongperiodslyinginbedawakebutnotmoving136.Methodologiesforanalyzingdataarenotstandardized,andalgorithmsforcalculationofsleepandcircadianparametersvaryacrossmanufacturers.Thereisalsovariabilityacrosstheinstrumentsthemselvesintermsofvalidityandconcordancewithothermeasuresofcircadianrhythms.
RECOMMENDEDMEASURE3:Morningness-EveningnessQuestionnaire(MEQ)137
Description:TheHorneandOstbergMorningness-EveningnessQuestionnaireconsistsof19self-reportquestionsthataskaboutbedtimesandwakingtimes,preferredtimesforactivitiesandalertness.Scoresrangefrom16to86,withhigherscoresindicatinggreatermorningnesspreference.
Measurementissues:Scoringneedstobeadjustedforage,sinceyoungerpeopletendtoexpressmoreeveningness.Scoresarealsonotnecessarilyconsistentacrosssubjectsfromdifferentpopulationsorcultures.Otherfactorsthatmayinfluencescoresincludeworkschedule,particularlyshiftwork.Scoresreflectcircadianpreferencetraitandthereforethescalecannotbeusedtomeasurechange138.
RECOMMENDEDMEASURE4:MunichChronotypeQuestionnaire(MCQ)139
Description:TheMCTQassesseschronotypebyusingself-reportedsleeppatternsonwork/schooldaysanddaysoff.Themidpointofthesleepperiodormid-sleepondaysoffisusedtodeterminethechronotype,andconsideredtobemoreofastate-likemeasurethantheMEQ.
Measurementissues:Mid-sleepondaysoffisinfluencedbysleepdebtthatoccursduringwork/schooldays,particularlyforlatechronotypeswhomustawakenearlyforwork/school.Useofanalarmclockondaysoffalsoskewstheresults,andcannotbeusedinshiftworkers.ItisamuchlesswidelyusedinstrumentthantheMEQ138.
Promisingmeasuresrequiringfurtherdevelopment
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• Geneexpressionpatterns140-142• Pupillarylightreflex143
Consideredbutnotrecommended
• Cortisol(toomanyotherfactorscanaffectdata)• Corebodytemperature(tooinvasive,melatoninfairlyequivalent)
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APPENDIXARS-Ia:Summaryofdiscussionofhowwelleachtaskmettheproposedcriteriafortaskevaluation.
Task:Electrodermalconductance(a)duringrestingstate(measureoftonicarousal);(b)inresponsetoatask
Construct:AROUSAL
1.HowstrongistheevidencethatthetaskprovidesavalidmeasureoftheRDoCconstruct?Verywidelyusedtest.
2.Howgoodistheevidenceaboutthepsychometricscharacteristicsofthetask(e.g.,internalreliability,testretest,floorandceilingeffects,practiceeffects,availabilityofalternateforms,longitudinalstability)?Reasonablygoodforlongitudinalstabilityandtest-retestreliabilityformeasureoftonicarousal;practiceeffectsforrepeatedmeasurementinresponsetostimuli.However,insufficientdataintermsofcorrelationwithtreatmentresponse.
3.Areparametersforadministeringthetask(e.g.,numberoftrials,stimuluscharacteristics,primarydependentmeasure)standardizedonanempiricalbasis?No.
4.Towhatextentisthetask(ordifferentversionsofthetask)suitableforuseacrosslab-basedstudies,clinicaltrials(asameasureoftargetengagementorclinicaloutcome),and/orhigh-throughputscreeningsettings?Nostandardizedparadigmsthathavebeenuse;hasnotbeenusedinclinicaloutcomestudies,althoughithasbeencorrelatedwithstressresponseandabnormalitiesreportedinpsychiatricpopulations.SeePeterLangstudies.
5.Isthetaskfreefromfloor/ceilingeffectssothatitcanbeusedacrossindividualswiththefullrangeofperformance/impairmentonthetasks?Unknown,buttherearenon-respondersintask-responseversion.
6.Canthetaskbeused(oradaptedforuse)withchildrenandotherspecialpopulations?Canitbeusedacrossagegroups?Canitbeusedacrossdifferentculturalsettings?Yes.
7.Canthetaskbeusedasastand-alonebehavioraltask?N/A
8.Isthetasksuitableforuseinhumansubjectsinavarietyoflabenvironments?Isthetaskfeasibleforadministrationacrosssites?Whatworkisneededtomakethetaskreadyforuseinclinicaltrials?
9.Areadequatenormativedataavailableacrossage,gender,education,ethnicity,SES?Somenormativedatainhealthyyoungadultsandwithrespecttotheseothervariables.
10.Isthetaskcurrentlyinwideusageorhasitsusebeenlimitedtoafewresearchgroups?Widelyused,butnotinrelationtotreatmentresponseinpsychiatricdisorders.
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11.Isthetasksensitivetowithin-personchange?Yesfortonicmeasure;repeatedstimulicanpossiblyleadtohabituation.Hasbeenusedinsomebiofeedbackstudiestoshowchange.
12.Canthetaskbeusedwithmethodstointerrogatebraincircuitry(e.g.,fMRI,EEG,etc.)?Yes
13.Canthetask(oritsanalog)beusedinanimals?Isananimalversionavailable?No.
14.Aretherelationshipsbetweentaskperformanceandneuralsignal(s)known?Somestudiescorrelatingfunctionalimagingwithelectrodermalskinresponse.
15.Aretherelationshipsbetweentaskperformanceandclinicalfeature(s)known?Associatedwithstress/anxiety.
16.Isthetaskfreelydistributed(i.e.,notcopyrighted)?Yes
17.DoesthetaskassessmultipleRDoCconstructsorisitspecifictojustone?Ifitassessesmultipleconstructs,doesitallowforunambiguousconclusionsaboutthetargetedconstruct?Affected/assessesmultipleconstructssuchaspositive/negativevalence,relatedtostress/anxiety.
18.Ifthereisnoexistingtaskavailableforaconstruct,isthereataskthatcouldbemodifiedtofittheconstruct?N/A
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APPENDIXARS-Ib:Summaryofdiscussionofhowwelleachtaskmettheproposedcriteriafortaskevaluation.
Task:Psychomotorvigilancetask(PVT)
Construct:AROUSAL
1.HowstrongistheevidencethatthetaskprovidesavalidmeasureoftheRDoCconstruct?Primarilyatestofalertness,whichisrelatedtoarousalandaffectedbysleep/sleeploss,circadianrhythm,timeontask.
2.Howgoodistheevidenceaboutthepsychometricscharacteristicsofthetask(e.g.,internalreliability,testretest,floorandceilingeffects,practiceeffects,availabilityofalternateforms,longitudinalstability)?Testneedstobedonemultipletimesduringthedayforeachtimepointifnotdoneundersleepdeprivationconditions;thereareceilingeffects.
3.Areparametersforadministeringthetask(e.g.,numberoftrials,stimuluscharacteristics,primarydependentmeasure)standardizedonanempiricalbasis?Yes.
4.Towhatextentisthetask(ordifferentversionsofthetask)suitableforuseacrosslab-basedstudies,clinicaltrials(asameasureoftargetengagementorclinicaloutcome),and/orhigh-throughputscreeningsettings?Maybeusedinthesesettings.
5.Isthetaskfreefromfloor/ceilingeffectssothatitcanbeusedacrossindividualswiththefullrangeofperformance/impairmentonthetasks?Ceilingeffects.
6.Canthetaskbeused(oradaptedforuse)withchildrenandotherspecialpopulations?Canitbeusedacrossagegroups?Canitbeusedacrossdifferentculturalsettings?Yes.
7.Canthetaskbeusedasastand-alonebehavioraltask?
8.Isthetasksuitableforuseinhumansubjectsinavarietyoflabenvironments?Isthetaskfeasibleforadministrationacrosssites?Whatworkisneededtomakethetaskreadyforuseinclinicaltrials?
9.Areadequatenormativedataavailableacrossage,gender,education,ethnicity,SES?Yes.
10.Isthetaskcurrentlyinwideusageorhasitsusebeenlimitedtoafewresearchgroups?Moderateuse.
11.Isthetasksensitivetowithin-personchange?Yes.
12.Canthetaskbeusedwithmethodstointerrogatebraincircuitry(e.g.,fMRI,EEG,etc.)?Yes.
13.Canthetask(oritsanalog)beusedinanimals?Isananimalversionavailable?No.
14.Aretherelationshipsbetweentaskperformanceandneuralsignal(s)known?No.
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15.Aretherelationshipsbetweentaskperformanceandclinicalfeature(s)known?RelatedtoADHD,sleepdeprivation.
16.Isthetaskfreelydistributed(i.e.,notcopyrighted)?Yes.
17.DoesthetaskassessmultipleRDoCconstructsorisitspecifictojustone?Ifitassessesmultipleconstructs,doesitallowforunambiguousconclusionsaboutthetargetedconstruct?Relatedtoattention/arousal.
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APPENDIXARS-Ic:Summaryofdiscussionofhowwelleachtaskmettheproposedcriteriafortaskevaluation.
Task:Pupillometryincontrolledcontext
Construct:AROUSAL
1.HowstrongistheevidencethatthetaskprovidesavalidmeasureoftheRDoCconstruct?Oneofthebettermeasuresofarousal.
2.Howgoodistheevidenceaboutthepsychometricscharacteristicsofthetask(e.g.,internalreliability,testretest,floorandceilingeffects,practiceeffects,availabilityofalternateforms,longitudinalstability)?Affectedbymanyfactors;within-andbetween-subjectvariabilitycanbeproblematic.Hassomeceilingandflooreffects.
3.Areparametersforadministeringthetask(e.g.,numberoftrials,stimuluscharacteristics,primarydependentmeasure)standardizedonanempiricalbasis?Moreworkneededonadministrationandanalysisstandardization.
4.Towhatextentisthetask(ordifferentversionsofthetask)suitableforuseacrosslab-basedstudies,clinicaltrials(asameasureoftargetengagementorclinicaloutcome),and/orhigh-throughputscreeningsettings?Suitableforclinicaltrials;maybemoresuitableforhigh-throughputastechnologyisdeveloped.
5.Isthetaskfreefromfloor/ceilingeffectssothatitcanbeusedacrossindividualswiththefullrangeofperformance/impairmentonthetasks?Reasonablygoodforthis.
6.Canthetaskbeused(oradaptedforuse)withchildrenandotherspecialpopulations?Canitbeusedacrossagegroups?Canitbeusedacrossdifferentculturalsettings?Yes.
7.Canthetaskbeusedasastand-alonebehavioraltask?No.
8.Isthetasksuitableforuseinhumansubjectsinavarietyoflabenvironments?Isthetaskfeasibleforadministrationacrosssites?Whatworkisneededtomakethetaskreadyforuseinclinicaltrials?Notenoughexperienceyet;needsmorework.
9.Areadequatenormativedataavailableacrossage,gender,education,ethnicity,SES?No.
10.Isthetaskcurrentlyinwideusageorhasitsusebeenlimitedtoafewresearchgroups?Notwidespreadbutuseincreasing.
11.Isthetasksensitivetowithin-personchange?Yes,butnotextensivestudies,mostlookingatwithin-subjectchangetosleeploss;alsowiththecaveatofvariability.
12.Canthetaskbeusedwithmethodstointerrogatebraincircuitry(e.g.,fMRI,EEG,etc.)?Yes.
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13.Canthetask(oritsanalog)beusedinanimals?Isananimalversionavailable?Yes;limited.
14.Aretherelationshipsbetweentaskperformanceandneuralsignal(s)known?Yes.
15.Aretherelationshipsbetweentaskperformanceandclinicalfeature(s)known?Yes,relatedtosleepiness,interest.
16.Isthetaskfreelydistributed(i.e.,notcopyrighted)?Yes
17.DoesthetaskassessmultipleRDoCconstructsorisitspecifictojustone?Ifitassessesmultipleconstructs,doesitallowforunambiguousconclusionsaboutthetargetedconstruct?Fairlytightlyrelatedtoarousal,mainissueisstandardization.
18.Ifthereisnoexistingtaskavailableforaconstruct,isthereataskthatcouldbemodifiedtofittheconstruct?
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APPENDIXARS-Id:Summaryofdiscussionofhowwelleachtaskmettheproposedcriteriafortaskevaluation.
Task:Heartratevariability
Construct:AROUSAL
1.HowstrongistheevidencethatthetaskprovidesavalidmeasureoftheRDoCconstruct?Providesinformationonparasympathetic/sympatheticNSbalance.
2.Howgoodistheevidenceaboutthepsychometricscharacteristicsofthetask(e.g.,internalreliability,testretest,floorandceilingeffects,practiceeffects,availabilityofalternateforms,longitudinalstability)?Isaffectedbyvariousfactors,canbeanoisymeasure.Inwideuse,reasonabletest-retestconsistency.
3.Areparametersforadministeringthetask(e.g.,numberoftrials,stimuluscharacteristics,primarydependentmeasure)standardizedonanempiricalbasis?Variabilityinadministrationandanalysis;recommendmoreworktostandardize.
4.Towhatextentisthetask(ordifferentversionsofthetask)suitableforuseacrosslab-basedstudies,clinicaltrials(asameasureoftargetengagementorclinicaloutcome),and/orhigh-throughputscreeningsettings?Easytoadminister,moreeasilyscalablethanmanyothermeasures.
5.Isthetaskfreefromfloor/ceilingeffectssothatitcanbeusedacrossindividualswiththefullrangeofperformance/impairmentonthetasks?
6.Canthetaskbeused(oradaptedforuse)withchildrenandotherspecialpopulations?Canitbeusedacrossagegroups?Canitbeusedacrossdifferentculturalsettings?
7.Canthetaskbeusedasastand-alonebehavioraltask?
8.Isthetasksuitableforuseinhumansubjectsinavarietyoflabenvironments?Isthetaskfeasibleforadministrationacrosssites?Whatworkisneededtomakethetaskreadyforuseinclinicaltrials?
9.Areadequatenormativedataavailableacrossage,gender,education,ethnicity,SES?Yes.
10.Isthetaskcurrentlyinwideusageorhasitsusebeenlimitedtoafewresearchgroups?Yes.
11.Isthetasksensitivetowithin-personchange?Yes,changesinresponsetointerventions.
12.Canthetaskbeusedwithmethodstointerrogatebraincircuitry(e.g.,fMRI,EEG,etc.)?Yes.
13.Canthetask(oritsanalog)beusedinanimals?Isananimalversionavailable?Yes.
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14.Aretherelationshipsbetweentaskperformanceandneuralsignal(s)known?Someinformationavailable.
15.Aretherelationshipsbetweentaskperformanceandclinicalfeature(s)known?Yes;associatedwithmood,anxiety,stress,drugeffects,etc.
16.Isthetaskfreelydistributed(i.e.,notcopyrighted)?Yes.
17.DoesthetaskassessmultipleRDoCconstructsorisitspecifictojustone?Ifitassessesmultipleconstructs,doesitallowforunambiguousconclusionsaboutthetargetedconstruct?Yes,fairlyspecificforarousal.
18.Ifthereisnoexistingtaskavailableforaconstruct,isthereataskthatcouldbemodifiedtofittheconstruct?
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APPENDIXARS-Ie:Summaryofdiscussionofhowwelleachtaskmettheproposedcriteriafortaskevaluation.
Task:Sleepspindlescharacteristics(density,amplitude,frequency,duration,topography)measuredbypolysomnography,particularlyinstageN2sleep.
Construct:SLEEP-WAKEFULNESS
1.HowstrongistheevidencethatthetaskprovidesavalidmeasureoftheRDoCconstruct?ValidasameasureofthalamocorticalcircuitrythatisinvolvedinNREMsleepprocess;mostinformationavailableforspindledensity.
2.Howgoodistheevidenceaboutthepsychometricscharacteristicsofthetask(e.g.,internalreliability,testretest,floorandceilingeffects,practiceeffects,availabilityofalternateforms,longitudinalstability)?Stablemeasurewithexcellenttest-retestreliability.
3.Areparametersforadministeringthetask(e.g.,numberoftrials,stimuluscharacteristics,primarydependentmeasure)standardizedonanempiricalbasis?EEGrecordingandvisualspindleidentificationstandardized,butthereissomevariabilityacrosslabsregardingfrequencydefinition.
4.Towhatextentisthetask(ordifferentversionsofthetask)suitableforuseacrosslab-basedstudies,clinicaltrials(asameasureoftargetengagementorclinicaloutcome),and/orhigh-throughputscreeningsettings?Dependsatpresentonperformingovernightsleepstudyinlaboratory,solesssuitableforhigh-throughputsettings.Needtodetermineifnapdatawouldbesufficient.
5.Isthetaskfreefromfloor/ceilingeffectssothatitcanbeusedacrossindividualswiththefullrangeofperformance/impairmentonthetasks?Yes.
6.Canthetaskbeused(oradaptedforuse)withchildrenandotherspecialpopulations?Canitbeusedacrossagegroups?Canitbeusedacrossdifferentculturalsettings?Yes.
7.Canthetaskbeusedasastand-alonebehavioraltask?N/A.
8.Areadequatenormativedataavailableacrossage,gender,education,ethnicity,SES?Pending.
9.Isthetaskcurrentlyinwideusageorhasitsusebeenlimitedtoafewresearchgroups?Usageincreasing.
10.Isthetasksensitivetowithin-personchange?Yes,butmoretrait-like.
11.Canthetaskbeusedwithmethodstointerrogatebraincircuitry(e.g.,fMRI,EEG,etc.)?Yes.
12.Canthetask(oritsanalog)beusedinanimals?Isananimalversionavailable?Yes.
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13.Aretherelationshipsbetweentaskperformanceandneuralsignal(s)known?Yes.
14.Aretherelationshipsbetweentaskperformanceandclinicalfeature(s)known?Yes.
15.Isthetaskfreelydistributed(i.e.,notcopyrighted)?Yes.
16.DoesthetaskassessmultipleRDoCconstructsorisitspecifictojustone?Ifitassessesmultipleconstructs,doesitallowforunambiguousconclusionsaboutthetargetedconstruct?Fairlyspecifictosleep,althoughassociatedwithcognitionaswellassleep.
17.Ifthereisnoexistingtaskavailableforaconstruct,isthereataskthatcouldbemodifiedtofittheconstruct?N/A
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APPENDIXARS-If:Summaryofdiscussionofhowwelleachtaskmettheproposedcriteriafortaskevaluation.
Task:MultipleSleepLatencyTest(MSLT)
Construct:SLEEP-WAKEFULNESS
1.HowstrongistheevidencethatthetaskprovidesavalidmeasureoftheRDoCconstruct?Strongmeasureofsleepiness;consideredagoldstandard.
2.Howgoodistheevidenceaboutthepsychometricscharacteristicsofthetask(e.g.,internalreliability,testretest,floorandceilingeffects,practiceeffects,availabilityofalternateforms,longitudinalstability)?Limitedonlyby“noise”relatedtovariability.
3.Areparametersforadministeringthetask(e.g.,numberoftrials,stimuluscharacteristics,primarydependentmeasure)standardizedonanempiricalbasis?Yes.
4.Towhatextentisthetask(ordifferentversionsofthetask)suitableforuseacrosslab-basedstudies,clinicaltrials(asameasureoftargetengagementorclinicaloutcome),and/orhigh-throughputscreeningsettings?Limitedbyneedtobeperformedinasleeplaboratory.
5.Isthetaskfreefromfloor/ceilingeffectssothatitcanbeusedacrossindividualswiththefullrangeofperformance/impairmentonthetasks?Yes,ceilingeffect.
6.Canthetaskbeused(oradaptedforuse)withchildrenandotherspecialpopulations?Canitbeusedacrossagegroups?Canitbeusedacrossdifferentculturalsettings?Yes.
7.Canthetaskbeusedasastand-alonebehavioraltask?Yes.
8.Isthetasksuitableforuseinhumansubjectsinavarietyoflabenvironments?Isthetaskfeasibleforadministrationacrosssites?Whatworkisneededtomakethetaskreadyforuseinclinicaltrials?Isusedinmanyofthesesettings.
9.Areadequatenormativedataavailableacrossage,gender,education,ethnicity,SES?Yes.
10.Isthetaskcurrentlyinwideusageorhasitsusebeenlimitedtoafewresearchgroups?Widelyused.
11.Isthetasksensitivetowithin-personchange?Yes.
12.Canthetaskbeusedwithmethodstointerrogatebraincircuitry(e.g.,fMRI,EEG,etc.)?Yes.
13.Canthetask(oritsanalog)beusedinanimals?Isananimalversionavailable?No.
14.Aretherelationshipsbetweentaskperformanceandneuralsignal(s)known?No.
15.Aretherelationshipsbetweentaskperformanceandclinicalfeature(s)known?Yes.
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16.Isthetaskfreelydistributed(i.e.,notcopyrighted)?Yes.
17.DoesthetaskassessmultipleRDoCconstructsorisitspecifictojustone?Ifitassessesmultipleconstructs,doesitallowforunambiguousconclusionsaboutthetargetedconstruct?Specificforsleepiness.
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APPENDIXARS-Ig:Summaryofdiscussionofhowwelleachtaskmettheproposedcriteriafortaskevaluation.
Task:Polysomnographically-definedsleeparchitecture(sleeplatency,wakefulnessaftersleeponset,totalsleeptime)
Construct:SLEEP-WAKEFULNESS
1. HowstrongistheevidencethatthetaskprovidesavalidmeasureoftheRDoCconstruct?Goldstandard.
2.Howgoodistheevidenceaboutthepsychometricscharacteristicsofthetask(e.g.,internalreliability,testretest,floorandceilingeffects,practiceeffects,availabilityofalternateforms,longitudinalstability)?Thereisaflooreffectonsomeparameters(eg,sleeplatencyandWASO),night-to-nightvariabilityandaccommodationeffectssleepinginthesleeplab.
3.Areparametersforadministeringthetask(e.g.,numberoftrials,stimuluscharacteristics,primarydependentmeasure)standardizedonanempiricalbasis?Yes.
4.Towhatextentisthetask(ordifferentversionsofthetask)suitableforuseacrosslab-basedstudies,clinicaltrials(asameasureoftargetengagementorclinicaloutcome),and/orhigh-throughputscreeningsettings?Dependsatpresentonperformingovernightsleepstudyinlaboratory,solesssuitableforhigh-throughputsettings.Needtodetermineifnapdatawouldbesufficient.
5.Isthetaskfreefromfloor/ceilingeffectssothatitcanbeusedacrossindividualswiththefullrangeofperformance/impairmentonthetasks?Canbeusedacrosswiderangeofindividualsbuttherearesomefloor/ceilingeffectsasnotedabove(2).
6.Canthetaskbeused(oradaptedforuse)withchildrenandotherspecialpopulations?Canitbeusedacrossagegroups?Canitbeusedacrossdifferentculturalsettings?Yes.
7.Canthetaskbeusedasastand-alonebehavioraltask?N/A.
8.Isthetasksuitableforuseinhumansubjectsinavarietyoflabenvironments?Isthetaskfeasibleforadministrationacrosssites?Whatworkisneededtomakethetaskreadyforuseinclinicaltrials?Suitableforuseinavarietyofenvironmentsandhasbeenusedextensivelyinmulti-siteclinicaltrials.
9.Areadequatenormativedataavailableacrossage,gender,education,ethnicity,SES?Yes.
10.Isthetaskcurrentlyinwideusageorhasitsusebeenlimitedtoafewresearchgroups?Widelyutilized.
11.Isthetasksensitivetowithin-personchange?Yes,butlimitedsomewhatbynight-to-nightvariability.
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12.Canthetaskbeusedwithmethodstointerrogatebraincircuitry(e.g.,fMRI,EEG,etc.)?Yes.
13.Canthetask(oritsanalog)beusedinanimals?Isananimalversionavailable?Yes.
14.Aretherelationshipsbetweentaskperformanceandneuralsignal(s)known?SleepEEGisaneuralsignal.
15.Aretherelationshipsbetweentaskperformanceandclinicalfeature(s)known?Yes.
16.Isthetaskfreelydistributed(i.e.,notcopyrighted)?Yes.
17.DoesthetaskassessmultipleRDoCconstructsorisitspecifictojustone?Ifitassessesmultipleconstructs,doesitallowforunambiguousconclusionsaboutthetargetedconstruct?Specificforthisconstruct.
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APPENDIXARS-Ih:Summaryofdiscussionofhowwelleachtaskmettheproposedcriteriafortaskevaluation.
Task:Slowwavemeasures(declineacrossthenightashomeostaticmeasure,NREMaverageslowwavepower)
Construct:SLEEP-WAKEFULNESS
1.HowstrongistheevidencethatthetaskprovidesavalidmeasureoftheRDoCconstruct?Definingelectrophysiologicalmarkerofsleep.
2.Howgoodistheevidenceaboutthepsychometricscharacteristicsofthetask(e.g.,internalreliability,testretest,floorandceilingeffects,practiceeffects,availabilityofalternateforms,longitudinalstability)?Somenight-to-nightvariability.
3.Areparametersforadministeringthetask(e.g.,numberoftrials,stimuluscharacteristics,primarydependentmeasure)standardizedonanempiricalbasis?Somevariabilityacrosslabsregardingmeasurement.
4.Towhatextentisthetask(ordifferentversionsofthetask)suitableforuseacrosslab-basedstudies,clinicaltrials(asameasureoftargetengagementorclinicaloutcome),and/orhigh-throughputscreeningsettings?Dependsatpresentonperformingovernightsleepstudyinlaboratory,solesssuitableforhigh-throughputsettings.Needtodetermineifnapdatawouldbesufficient.
5.Isthetaskfreefromfloor/ceilingeffectssothatitcanbeusedacrossindividualswiththefullrangeofperformance/impairmentonthetasks?TherecanbeflooreffectsinindividualswithoutmuchSWA;canbeconfoundedinelderlywithgeneralizedEEGslowing.
6.Canthetaskbeused(oradaptedforuse)withchildrenandotherspecialpopulations?Canitbeusedacrossagegroups?Canitbeusedacrossdifferentculturalsettings?Yes.
7.Canthetaskbeusedasastand-alonebehavioraltask?No;needstobecorrelatedwithothermeasures.
8.Isthetasksuitableforuseinhumansubjectsinavarietyoflabenvironments?Isthetaskfeasibleforadministrationacrosssites?Whatworkisneededtomakethetaskreadyforuseinclinicaltrials?Easytocollectdata,notalllabsanalyzeslowwaves.
9.Areadequatenormativedataavailableacrossage,gender,education,ethnicity,SES?Yes.
10.Isthetaskcurrentlyinwideusageorhasitsusebeenlimitedtoafewresearchgroups?Datacollectedwidelybutnotanalyzedinmanylabs.
11.Isthetasksensitivetowithin-personchange?Yes.
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12.Canthetaskbeusedwithmethodstointerrogatebraincircuitry(e.g.,fMRI,EEG,etc.)?Yes.
13.Canthetask(oritsanalog)beusedinanimals?Isananimalversionavailable?Yes.
14.Aretherelationshipsbetweentaskperformanceandneuralsignal(s)known?Yes.
15.Aretherelationshipsbetweentaskperformanceandclinicalfeature(s)known?Yes.
16.Isthetaskfreelydistributed(i.e.,notcopyrighted)?Yes.
17.DoesthetaskassessmultipleRDoCconstructsorisitspecifictojustone?Ifitassessesmultipleconstructs,doesitallowforunambiguousconclusionsaboutthetargetedconstruct?Specifictosleep.
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APPENDIXARS-Ii:Summaryofdiscussionofhowwelleachtaskmettheproposedcriteriafortaskevaluation.
Task:InsomniaSeverityIndex(ISI)
Construct:SLEEP-WAKEFULNESS
1.HowstrongistheevidencethatthetaskprovidesavalidmeasureoftheRDoCconstruct?Validmeasureofinsomniaanddaytimeconsequences.
2.Howgoodistheevidenceaboutthepsychometricscharacteristicsofthetask(e.g.,internalreliability,testretest,floorandceilingeffects,practiceeffects,availabilityofalternateforms,longitudinalstability)?Excellent.
3.Areparametersforadministeringthetask(e.g.,numberoftrials,stimuluscharacteristics,primarydependentmeasure)standardizedonanempiricalbasis?Yes.
4.Towhatextentisthetask(ordifferentversionsofthetask)suitableforuseacrosslab-basedstudies,clinicaltrials(asameasureoftargetengagementorclinicaloutcome),and/orhigh-throughputscreeningsettings?Easilyused;shortself-administeredscale.
5.Isthetaskfreefromfloor/ceilingeffectssothatitcanbeusedacrossindividualswiththefullrangeofperformance/impairmentonthetasks?Yes.
6.Canthetaskbeused(oradaptedforuse)withchildrenandotherspecialpopulations?Canitbeusedacrossagegroups?Canitbeusedacrossdifferentculturalsettings?Notvalidatedinchildren,hasbeentranslatedintoseverallanguages.
7.Canthetaskbeusedasastand-alonebehavioraltask?Notabehavioraltask.
8.Isthetasksuitableforuseinhumansubjectsinavarietyoflabenvironments?Isthetaskfeasibleforadministrationacrosssites?Whatworkisneededtomakethetaskreadyforuseinclinicaltrials?Usedwidelyinclinicaltrials.
9.Areadequatenormativedataavailableacrossage,gender,education,ethnicity,SES?Yes.
10.Isthetaskcurrentlyinwideusageorhasitsusebeenlimitedtoafewresearchgroups?Widelyused.
11.Isthetasksensitivetowithin-personchange?Yes.
12.Canthetaskbeusedwithmethodstointerrogatebraincircuitry(e.g.,fMRI,EEG,etc.)?N/A.
13.Canthetask(oritsanalog)beusedinanimals?Isananimalversionavailable?N/A.
14.Aretherelationshipsbetweentaskperformanceandneuralsignal(s)known?Yes.
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15.Aretherelationshipsbetweentaskperformanceandclinicalfeature(s)known?Yes.
16.Isthetaskfreelydistributed(i.e.,notcopyrighted)?Yes.
17.DoesthetaskassessmultipleRDoCconstructsorisitspecifictojustone?Ifitassessesmultipleconstructs,doesitallowforunambiguousconclusionsaboutthetargetedconstruct?Measuresinsomnia.
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APPENDIXARS-Ij:Summaryofdiscussionofhowwelleachtaskmettheproposedcriteriafortaskevaluation.
Task:FingertappingMotorSequenceTask(MST)
Construct:SLEEP-WAKEFULNESS
1.HowstrongistheevidencethatthetaskprovidesavalidmeasureoftheRDoCconstruct?Validmeasureofsleepdependentmemoryconsolidation.
2.Howgoodistheevidenceaboutthepsychometricscharacteristicsofthetask(e.g.,internalreliability,testretest,floorandceilingeffects,practiceeffects,availabilityofalternateforms,longitudinalstability)?Gooddataontheseparameters.
3.Areparametersforadministeringthetask(e.g.,numberoftrials,stimuluscharacteristics,primarydependentmeasure)standardizedonanempiricalbasis?Yes.
4.Towhatextentisthetask(ordifferentversionsofthetask)suitableforuseacrosslab-basedstudies,clinicaltrials(asameasureoftargetengagementorclinicaloutcome),and/orhigh-throughputscreeningsettings?Needstobedonetwiceseparatedby12or24hrs,whichcanbelimiting.
5.Isthetaskfreefromfloor/ceilingeffectssothatitcanbeusedacrossindividualswiththefullrangeofperformance/impairmentonthetasks?Flooreffectinelderly(maynotshowsleep-dependentlearning).
6.Canthetaskbeused(oradaptedforuse)withchildrenandotherspecialpopulations?Canitbeusedacrossagegroups?Canitbeusedacrossdifferentculturalsettings?Nonormsyetinchildren.Age-relatedchangesnotwellstudied.
7.Canthetaskbeusedasastand-alonebehavioraltask?Yes.
8.Isthetasksuitableforuseinhumansubjectsinavarietyoflabenvironments?Isthetaskfeasibleforadministrationacrosssites?Whatworkisneededtomakethetaskreadyforuseinclinicaltrials?Feasibletouseacrosssites.Usedinclinicaltrials.
9.Areadequatenormativedataavailableacrossage,gender,education,ethnicity,SES?No.
10.Isthetaskcurrentlyinwideusageorhasitsusebeenlimitedtoafewresearchgroups?Mostwidelyusedprobeforsleep-dependentlearning,butnotalotoflabsworkingonthis.
11.Isthetasksensitivetowithin-personchange?Yes.
12.Canthetaskbeusedwithmethodstointerrogatebraincircuitry(e.g.,fMRI,EEG,etc.)?Yes.
13.Canthetask(oritsanalog)beusedinanimals?Isananimalversionavailable?N/A.
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14.Aretherelationshipsbetweentaskperformanceandneuralsignal(s)known?Neuroimagingstudiesexist,butnotmany.
15.Aretherelationshipsbetweentaskperformanceandclinicalfeature(s)known?Yes.
16.Isthetaskfreelydistributed(i.e.,notcopyrighted)?Yes.
17.DoesthetaskassessmultipleRDoCconstructsorisitspecifictojustone?Ifitassessesmultipleconstructs,doesitallowforunambiguousconclusionsaboutthetargetedconstruct?Measuressleep-dependentlearning/restorativeaspectsofsleepfairlyspecifically.
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APPENDIXARS-Ik:Summaryofdiscussionofhowwelleachtaskmettheproposedcriteriafortaskevaluation.
Task:Dimlightmelatoninonset(DLMO)
Construct:CIRCADIANRHYTHMS
1.HowstrongistheevidencethatthetaskprovidesavalidmeasureoftheRDoCconstruct?Verystrong.
2.Howgoodistheevidenceaboutthepsychometricscharacteristicsofthetask(e.g.,internalreliability,testretest,floorandceilingeffects,practiceeffects,availabilityofalternateforms,longitudinalstability)?Probablythebestmarkerforcircadianphase;caveatisthatsomesubjectshavelowlevelsofmelatonin.
3.Areparametersforadministeringthetask(e.g.,numberoftrials,stimuluscharacteristics,primarydependentmeasure)standardizedonanempiricalbasis?Yes.
4.Towhatextentisthetask(ordifferentversionsofthetask)suitableforuseacrosslab-basedstudies,clinicaltrials(asameasureoftargetengagementorclinicaloutcome),and/orhigh-throughputscreeningsettings?Notidealforhigh-throughputstudies,otherwiseusefulinclinicalresearch/trials.
5.Isthetaskfreefromfloor/ceilingeffectssothatitcanbeusedacrossindividualswiththefullrangeofperformance/impairmentonthetasks?Fewsubjectsmayhavelowlevels(flooreffect).
6.Canthetaskbeused(oradaptedforuse)withchildrenandotherspecialpopulations?Canitbeusedacrossagegroups?Canitbeusedacrossdifferentculturalsettings?Yes.
7.Canthetaskbeusedasastand-alonebehavioraltask?N/A
8.Isthetasksuitableforuseinhumansubjectsinavarietyoflabenvironments?Isthetaskfeasibleforadministrationacrosssites?Whatworkisneededtomakethetaskreadyforuseinclinicaltrials?Yes.
9.Areadequatenormativedataavailableacrossage,gender,education,ethnicity,SES?Somedatainpublishedstudies.
10.Isthetaskcurrentlyinwideusageorhasitsusebeenlimitedtoafewresearchgroups?Usedinanumberoflabs;samplesneedtoberunbyqualifiedlabs.
11.Isthetasksensitivetowithin-personchange?Yes.
12.Canthetaskbeusedwithmethodstointerrogatebraincircuitry(e.g.,fMRI,EEG,etc.)?N/A.
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13.Canthetask(oritsanalog)beusedinanimals?Isananimalversionavailable?Yes.
14.Aretherelationshipsbetweentaskperformanceandneuralsignal(s)known?Yes.
15.Aretherelationshipsbetweentaskperformanceandclinicalfeature(s)known?Moredataneeded.
16.Isthetaskfreelydistributed(i.e.,notcopyrighted)?Yes.
17.DoesthetaskassessmultipleRDoCconstructsorisitspecifictojustone?Ifitassessesmultipleconstructs,doesitallowforunambiguousconclusionsaboutthetargetedconstruct?Fairlyspecificforcircadianphase.
18.Ifthereisnoexistingtaskavailableforaconstruct,isthereataskthatcouldbemodifiedtofittheconstruct?
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APPENDIXARS-Il:Summaryofdiscussionofhowwelleachtaskmettheproposedcriteriafortaskevaluation.
Task:Actigraphymeasuredlongitudinally(cosinoranalysis:acrophase,mesor,amplitude)
Construct:CIRCADIANRHYTHMS
1.HowstrongistheevidencethatthetaskprovidesavalidmeasureoftheRDoCconstruct?Fairlystrongbasedonactivitypattern.
2.Howgoodistheevidenceaboutthepsychometricscharacteristicsofthetask(e.g.,internalreliability,testretest,floorandceilingeffects,practiceeffects,availabilityofalternateforms,longitudinalstability)?Needsoptimization.
3.Areparametersforadministeringthetask(e.g.,numberoftrials,stimuluscharacteristics,primarydependentmeasure)standardizedonanempiricalbasis?Yes.
4.Towhatextentisthetask(ordifferentversionsofthetask)suitableforuseacrosslab-basedstudies,clinicaltrials(asameasureoftargetengagementorclinicaloutcome),and/orhigh-throughputscreeningsettings?Easilyusedinclinicalresearch,canbeusedforlargepopulationbasedstudies.
5.Isthetaskfreefromfloor/ceilingeffectssothatitcanbeusedacrossindividualswiththefullrangeofperformance/impairmentonthetasks?Flooreffectifsubjectsdonotmovearoundmuch.
6.Canthetaskbeused(oradaptedforuse)withchildrenandotherspecialpopulations?Canitbeusedacrossagegroups?Canitbeusedacrossdifferentculturalsettings?Yes.
7.Canthetaskbeusedasastand-alonebehavioraltask?N/A
8.Isthetasksuitableforuseinhumansubjectsinavarietyoflabenvironments?Isthetaskfeasibleforadministrationacrosssites?Whatworkisneededtomakethetaskreadyforuseinclinicaltrials?Morenormativedata.Moreanalytictoolstobetteranalyzeactivitydata(e.g.,functionaldataanalysisapproach).
9.Areadequatenormativedataavailableacrossage,gender,education,ethnicity,SES?Moreneeded.
10.Isthetaskcurrentlyinwideusageorhasitsusebeenlimitedtoafewresearchgroups?Fairlycommonlyusedincircadianresearch.
11.Isthetasksensitivetowithin-personchange?Yes.
12.Canthetaskbeusedwithmethodstointerrogatebraincircuitry(e.g.,fMRI,EEG,etc.)?N/A
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13.Canthetask(oritsanalog)beusedinanimals?Isananimalversionavailable?Yes(activitymonitoringcommonlyused).
14.Aretherelationshipsbetweentaskperformanceandneuralsignal(s)known?Unknown.
15.Aretherelationshipsbetweentaskperformanceandclinicalfeature(s)known?Somedatainpsychiatricpopulations.
16.Isthetaskfreelydistributed(i.e.,notcopyrighted)?Needtobuysoftware.
17.DoesthetaskassessmultipleRDoCconstructsorisitspecifictojustone?Ifitassessesmultipleconstructs,doesitallowforunambiguousconclusionsaboutthetargetedconstruct?DatacanalsoassessSleep/WakefulnessandArousalconstructs.
18.Ifthereisnoexistingtaskavailableforaconstruct,isthereataskthatcouldbemodifiedtofittheconstruct?
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APPENDIXARS-Im:Summaryofdiscussionofhowwelleachtaskmettheproposedcriteriafortaskevaluation.
Task:MunichChronotypeQuestionnaire
Construct:CIRCADIANRHYTHMS
1.HowstrongistheevidencethatthetaskprovidesavalidmeasureoftheRDoCconstruct?Measureschronotype.IncontrasttothemorewidelyusedMEQ,whichisbasedonself-reportedpreferencesforsleepschedule,thisquestionnairedetermineschronotypebasedonreportedsleepschedules.
2.Howgoodistheevidenceaboutthepsychometricscharacteristicsofthetask(e.g.,internalreliability,testretest,floorandceilingeffects,practiceeffects,availabilityofalternateforms,longitudinalstability)?Hassomelimitations,suchasthatitisnotaccurateforindividualswhousealarmclockstoawakenondaysofffromwork.Notvalidatedinshiftworkers.
3.Areparametersforadministeringthetask(e.g.,numberoftrials,stimuluscharacteristics,primarydependentmeasure)standardizedonanempiricalbasis?Yes.
4.Towhatextentisthetask(ordifferentversionsofthetask)suitableforuseacrosslab-basedstudies,clinicaltrials(asameasureoftargetengagementorclinicaloutcome),and/orhigh-throughputscreeningsettings?Maybeusedinallthesesituations.
5.Isthetaskfreefromfloor/ceilingeffectssothatitcanbeusedacrossindividualswiththefullrangeofperformance/impairmentonthetasks?Yes.
6.Canthetaskbeused(oradaptedforuse)withchildrenandotherspecialpopulations?Canitbeusedacrossagegroups?Canitbeusedacrossdifferentculturalsettings?Yes,althoughsocioculturalfactorscanaffectresults.Pediatricversionavailable.
7.Canthetaskbeusedasastand-alonebehavioraltask?Yes.
8.Isthetasksuitableforuseinhumansubjectsinavarietyoflabenvironments?Isthetaskfeasibleforadministrationacrosssites?Whatworkisneededtomakethetaskreadyforuseinclinicaltrials?Maybeusedinthesesettings;morenormativedataneeded.
9.Areadequatenormativedataavailableacrossage,gender,education,ethnicity,SES?No,moreneeded.
10.Isthetaskcurrentlyinwideusageorhasitsusebeenlimitedtoafewresearchgroups?LesswidelyusedthantheMEQ.
11.Isthetasksensitivetowithin-personchange?Notgenerallyusedforthispurpose;chronotypeatraitmarker.
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12.Canthetaskbeusedwithmethodstointerrogatebraincircuitry(e.g.,fMRI,EEG,etc.)?N/A
13.Canthetask(oritsanalog)beusedinanimals?Isananimalversionavailable?N/A
14.Aretherelationshipsbetweentaskperformanceandneuralsignal(s)known?Notspecificallystudied.
15.Aretherelationshipsbetweentaskperformanceandclinicalfeature(s)known?Yes.
16.Isthetaskfreelydistributed(i.e.,notcopyrighted)?Yes,maybedownloadedbutwebsiteasksthatpermissionforuseberequested;nochargeindicated.
17.DoesthetaskassessmultipleRDoCconstructsorisitspecifictojustone?Ifitassessesmultipleconstructs,doesitallowforunambiguousconclusionsaboutthetargetedconstruct?Assesseschronotype.
18.Ifthereisnoexistingtaskavailableforaconstruct,isthereataskthatcouldbemodifiedtofittheconstruct?
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APPENDIXARS-In:Summaryofdiscussionofhowwelleachtaskmettheproposedcriteriafortaskevaluation.
Task:HorneandOstbergMorningness-EveningnessQuestionnaire(MEQ)
Construct:CIRCADIANRHYTHMS
1.HowstrongistheevidencethatthetaskprovidesavalidmeasureoftheRDoCconstruct?Stronglycorrelatedwithbedandwakingtimes;strongevidenceforvalidity.
2.Howgoodistheevidenceaboutthepsychometricscharacteristicsofthetask(e.g.,internalreliability,testretest,floorandceilingeffects,practiceeffects,availabilityofalternateforms,longitudinalstability)?Dataavailableconfirmingreliability,stabilityinbothadultandchild-adolescentversions;test-retestdatamorescant.
3.Areparametersforadministeringthetask(e.g.,numberoftrials,stimuluscharacteristics,primarydependentmeasure)standardizedonanempiricalbasis?Yes
4.Towhatextentisthetask(ordifferentversionsofthetask)suitableforuseacrosslab-basedstudies,clinicaltrials(asameasureoftargetengagementorclinicaloutcome),and/orhigh-throughputscreeningsettings?Takesonlyminutestocomplete,sosuitableforclinicaltrialsandhigh-throughputsettings.
5.Isthetaskfreefromfloor/ceilingeffectssothatitcanbeusedacrossindividualswiththefullrangeofperformance/impairmentonthetasks?Yes.
6.Canthetaskbeused(oradaptedforuse)withchildrenandotherspecialpopulations?Canitbeusedacrossagegroups?Canitbeusedacrossdifferentculturalsettings?Hasbeentranslatedintoseverallanguagesandapediatricversionisavailable.
7.Canthetaskbeusedasastand-alonebehavioraltask?Yes.
8.Isthetasksuitableforuseinhumansubjectsinavarietyoflabenvironments?Isthetaskfeasibleforadministrationacrosssites?Whatworkisneededtomakethetaskreadyforuseinclinicaltrials?Yes,canbeusedinthesesettingsandinclinicaltrials.
9.Areadequatenormativedataavailableacrossage,gender,education,ethnicity,SES?Somenormativedata(cut-offscores)availableinyoungadults,butvariousfactors(age,gender,socioeconomiclevelcanaffectdistributionofscores).
10.Isthetaskcurrentlyinwideusageorhasitsusebeenlimitedtoafewresearchgroups?Fairlywideusage.
11.Isthetasksensitivetowithin-personchange?N/A
12.Canthetaskbeusedwithmethodstointerrogatebraincircuitry(e.g.,fMRI,EEG,etc.)?N/A
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13.Canthetask(oritsanalog)beusedinanimals?Isananimalversionavailable?N/A
14.Aretherelationshipsbetweentaskperformanceandneuralsignal(s)known?N/A
15.Aretherelationshipsbetweentaskperformanceandclinicalfeature(s)known?Correlatedwithbiologicalmarkersofcircadianphase.
16.Isthetaskfreelydistributed(i.e.,notcopyrighted)?Yes.
17.DoesthetaskassessmultipleRDoCconstructsorisitspecifictojustone?Ifitassessesmultipleconstructs,doesitallowforunambiguousconclusionsaboutthetargetedconstruct?Specificforchronotype.
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APPENDIXA:RDOCMATRIXDOMAIN,CONSTRUCTSANDSUBCONSTRUCTDEFINITIONS
AsdefinedduringtheinitialRDoCworkshops.
Arousal/RegulatorySystems:Systemsresponsibleforgeneratingactivationofneuralsystemsasappropriateforvariouscontexts,andprovidingappropriatehomeostaticregulationofsuchsystemsasenergybalanceandsleep.
o Arousal:Arousalisacontinuumofsensitivityoftheorganismtostimuli,bothexternalandinternal.Arousal:
§ facilitatesinteractionwiththeenvironmentinacontext-specificmanner(e.g.,underconditionsofthreat,somestimulimustbeignoredwhilesensitivitytoandresponsestoothersisenhanced,asexemplifiedinthestartlereflex);
§ canbeevokedbyeitherexternal/environmentalstimuliorinternalstimuli(e.g.,emotionsandcognition);
§ canbemodulatedbythephysicalcharacteristicsandmotivationalsignificanceofstimuli;
§ variesalongacontinuumthatcanbequantifiedinanybehavioralstate,includingwakefulnessandlow-arousalstatesincludingsleep,anesthesia,andcoma;
§ isdistinctfrommotivationandvalencebutcanco-varywithintensityofmotivationandvalence;
§ maybeassociatedwithincreasedordecreasedlocomotoractivity;and§ canberegulatedbyhomeostaticdrives(e.g.,hunger,sleep,thirst,sex).
o CircadianRhythms:CircadianRhythmsareendogenousself-sustainingoscillationsthatorganizethetimingofbiologicalsystemstooptimizephysiologyandbehavior,andhealth.CircadianRhythms:
§ aresynchronizedbyrecurringenvironmentalcues;§ anticipatetheexternalenvironment;§ alloweffectiveresponsetochallengesandopportunitiesinthephysicaland
socialenvironment;§ modulatehomeostasiswithinthebrainandother(central/peripheral)
systems,tissuesandorgans;and§ areevidentacrosslevelsoforganizationincludingmolecules,cells,circuits,
systems,organisms,andsocialsystems.o Sleepandwakefulness:Sleepandwakefulnessareendogenous,recurring,
behavioralstatesthatreflectcoordinatedchangesinthedynamicfunctionalorganizationofthebrainandthatoptimizephysiology,behavior,andhealth.
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Homeostaticandcircadianprocessesregulatethepropensityforwakefulnessandsleep.Sleep:
§ isreversible,typicallycharacterizedbyposturalrecumbence,behavioralquiescence,andreducedresponsiveness;
§ hasacomplexarchitecturewithpredictablecyclingofNREM/REMstatesortheirdevelopmentalequivalents.NREMandREMsleephavedistinctneuralsubstrates(circuitry,transmitters,modulators)andEEGoscillatoryproperties
§ intensityanddurationisaffectedbyhomeostaticregulation;§ isaffectedbyexperiencesduringwakefulness;§ isevidentatcellular,circuit,andsystemlevels;and§ hasrestorativeandtransformativeeffectsthatoptimizeneurobehavioral
functionsduringwakefulness.
CognitiveSystems:Systemsresponsibleforvariouscognitiveprocesses(e.g.,attention,perception,memory,language,andcognitivecontrol).
o Attention:Attentionreferstoarangeofprocessesthatregulateaccesstocapacity-limitedsystems,suchasawareness,higherperceptualprocesses,andmotoraction.Theconceptsofcapacitylimitationandcompetitionareinherenttotheconceptsofselectiveanddividedattention.
o Perception:Perceptionreferstotheprocess(es)thatperformcomputationsonsensorydatatoconstructandtransformrepresentationsoftheexternalenvironment,acquireinformationfrom,andmakepredictionsabout,theexternalworld,andguideaction.
o DeclarativeMemory:Declarativememoryistheacquisitionorencoding,storageandconsolidation,andretrievalofrepresentationsoffactsandevents.Declarativememoryprovidesthecriticalsubstrateforrelationalrepresentations—i.e.,forspatial,temporal,andothercontextualrelationsamongitems,contributingtorepresentationsofevents(episodicmemory)andtheintegrationandorganizationoffactualknowledge(semanticmemory).Theserepresentationsfacilitatetheinferentialandflexibleextractionofnewinformationfromtheserelationships.
o Language:Languageisasystemofsharedsymbolicrepresentationsoftheworld,theselfandabstractconceptsthatsupportsthoughtandcommunication.
o CognitiveControl:Asystemthatmodulatestheoperationofothercognitiveandemotionalsystems,intheserviceofgoal-directedbehavior,whenprepotentmodesofrespondingarenotadequatetomeetthedemandsofthecurrentcontext.Additionally,controlprocessesareengagedinthecaseofnovelcontexts,whereappropriateresponsesneedtobeselectedfromamongcompetingalternatives.
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o WorkingMemory:WorkingMemoryistheactivemaintenanceandflexibleupdatingofgoal/taskrelevantinformation(items,goals,strategies,etc.)inaformthathaslimitedcapacityandresistsinterference.Theserepresentations:mayinvolveflexiblebindingofrepresentations;maybecharacterizedbytheabsenceofexternalsupportfortheinternallymaintainedrepresentations;andarefrequentlytemporary,thoughthismaybeduetoongoinginterference.Itinvolvesactivemaintenance,flexibleupdating,limitedcapacity,andinterferencecontrol.
NegativeValenceSystems:Systemsprimarilyresponsibleforresponsestoaversivesituationsorcontexts,suchas:
o Responsestoacutethreat(Fear):Activationofthebrain’sdefensivemotivationalsystemtopromotebehaviorsthatprotecttheorganismfromperceiveddanger.Normalfearinvolvesapatternofadaptiveresponsestoconditionedorunconditionedthreatstimuli(exteroceptiveorinteroceptive).Fearcaninvolveinternalrepresentationsandcognitiveprocessing,andcanbemodulatedbyavarietyoffactors.
o Responsestopotentialharm(Anxiety):Activationofabrainsysteminwhichharmmaypotentiallyoccurbutisdistant,ambiguous,orlow/uncertaininprobability,characterizedbyapatternofresponsessuchasenhancedriskassessment(vigilance).Theseresponsestolowimminencethreatsarequalitativelydifferentthanthehighimminencethreatbehaviorsthatcharacterizefear.
o Responsestosustainedthreat:Anaversiveemotionalstatecausedbyprolonged(i.e.,weekstomonths)exposuretointernaland/orexternalcondition(s),state(s),orstimulithatareadaptivetoescapeoravoid.Theexposuremaybeactualoranticipated;thechangesinaffect,cognition,physiology,andbehaviorcausedbysustainedthreatpersistintheabsenceofthethreat,andcanbedifferentiatedfromthosechangesevokedbyacutethreat.
o Frustrativenon-reward:Reactionselicitedinresponsetowithdrawal/preventionofreward,i.e.,bytheinabilitytoobtainpositiverewardsfollowingrepeatedorsustainedefforts.
o Loss:Astateofdeprivationofamotivationallysignificantcon-specific,object,orsituation.Lossmaybesocialornon-socialandmayincludepermanentorsustainedlossofshelter,behavioralcontrol,status,lovedones,orrelationships.Theresponsetolossmaybeepisodic(e.g.,grief)orsustained.
PositiveValenceSystems:Systemsprimarilyresponsibleforresponsestopositivemotivationalsituationsorcontexts,suchas:
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o Approachmotivation:Amulti-facetedconstructinvolvingmechanisms/processesthatregulatethedirectionandmaintenanceofapproachbehaviorinfluencedbypre-existingtendencies,learning,memory,stimuluscharacteristics,anddeprivationstates.Approachbehaviorcanbedirectedtowardinnateoracquiredcues(i.e.,unconditionedvs.learnedstimuli),implicitorexplicitgoals;itcanconsistofgoal-directedorPavlovianconditionedresponses.Componentprocessesincluderewardvaluation,effortvaluation/willingnesstowork,expectancy/rewardpredictionerror,andactionselection/decisionmaking.
§ Rewardvaluation:Processesbywhichtheprobabilityandbenefitsofaprospectiveoutcomearecomputedandcalibratedbyreferencetoexternalinformation,socialcontext(e.g.,groupinput,counterfactualcomparisons),and/orpriorexperience.Thiscalibrationisinfluencedbypre-existingbiases,learning,memory,stimuluscharacteristics,anddeprivationstates.Rewardvaluationmayinvolvetheassignmentofincentivesaliencetostimuli.
§ Effortvaluation/Willingnesstowork:Processesbywhichthecost(s)ofobtaininganoutcomeiscomputed;tendencytoovercomeresponsecoststoobtainareinforcer.
§ Expectancy/Rewardpredictionerror:Astatetriggeredbyexposuretointernalorexternalstimuli,experiencesorcontextsthatpredictthepossibilityofreward.Rewardexpectationcanaltertheexperienceofanoutcomeandcaninfluencetheuseofresources(e.g.,cognitiveresources).
§ Actionselection/Preference-baseddecisionmaking:Processesinvolvinganevaluationofcosts/benefitsandoccurringinthecontextofmultiplepotentialchoicesbeingavailablefordecision-making.
o Initialresponsivenesstorewardattainment:Mechanisms/processesassociatedwithhedonicresponses—asreflectedinsubjectiveexperiences,behavioralresponses,and/orengagementoftheneuralsystemstoapositivereinforcer—andculminationofrewardseeking.
o Sustained/Longer-termresponsivenesstorewardattainment:Mechanisms/processesassociatedwiththeterminationofrewardseeking,e.g.,satisfaction,satiation,regulationofconsummatorybehavior.
o RewardLearning:Aprocessbywhichorganismsacquireinformationaboutstimuli,actions,andcontextsthatpredictpositiveoutcomes,andbywhichbehaviorismodifiedwhenanovelrewardoccursoroutcomesarebetterthanexpected.Rewardlearningisatypeofreinforcementlearning,andsimilarprocessesmaybeinvolvedinlearningrelatedtonegativereinforcement.
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o Habit:Sequential,repetitive,motor,orcognitivebehaviorselicitedbyexternalorinternaltriggersthat,onceinitiated,cangotocompletionwithoutconstantconsciousoversight.Habitscanbeadaptivebyvirtueoffreeingupcognitiveresources.Habitformationisafrequentconsequenceofrewardlearning,butitsexpressioncanbecomeresistanttochangesinoutcomevalue.Relatedbehaviorscouldbepathologicalexpressionofaprocessthatundernormalcircumstancessubservesadaptivegoals.
SystemsforSocialProcesses:Systemsthatmediateprocessestointerpersonalsettingsofvarioustypes,includingperceptionandinterpretationofothers’actions.
o AffiliationandAttachment:Affiliationisengagementinpositivesocialinteractionswithotherindividuals.Attachmentisselectiveaffiliationasaconsequenceofthedevelopmentofasocialbond.AffiliationandAttachmentaremoderatedbysocialinformationprocessing(processingofsocialcues)andsocialmotivation.Affiliationisabehavioralconsequenceofsocialmotivationandcanmanifestitselfinsocialapproachbehaviors.AffiliationandAttachmentrequiredetectionofandattentiontosocialcues,aswellassociallearningandmemoryassociatedwiththeformationofrelationships.AffiliationandAttachmentincludeboththepositivephysiologicalconsequencesofsocialinteractionsandthebehavioralandphysiologicalconsequencesofdisruptionstosocialrelationships.ClinicalmanifestationsofdisruptionsinAffiliationandAttachmentincludesocialwithdrawal,socialindifferenceandanhedonia,andover-attachment.
o SocialCommunication:Adynamicprocessthatincludesbothreceptiveandproductiveaspectsusedforexchangeofsociallyrelevantinformation.Socialcommunicationisessentialfortheintegrationandmaintenanceoftheindividualinthesocialenvironment.Thisconstructisreciprocalandinteractive,andsocialcommunicationabilitiesmayappearveryearlyinlife.Socialcommunicationisdistinguishablefromothercognitivesystems(e.g.,perception,cognitivecontrol,memory,attention)inthatitparticularlyinvolvesinteractionswithconspecifics.Theunderlyingneuralsubstratesofsocialcommunicationevolvedtosupportbothautomatic/reflexiveandvolitionalcontrol,includingthemotivationandabilitytoengageinsocialcommunication.Receptiveaspectsmaybeimplicitorexplicit;examplesincludeaffectrecognition,facialrecognitionandcharacterization.Productiveaspectsincludeeyecontact,expressivereciprocation,andgazefollowing.Althoughfacialcommunicationwassetasideasaseparatesub-constructforthepurposesofidentifyingmatrixelements,socialcommunicationtypicallyutilizesinformationfromseveralmodalities,includingfacial,vocal,gestural,postural,andolfactoryprocessing.SocialCommunicationwasorganizedintothefollowingsub-constructs:
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§ ReceptionofFacialCommunication:Thecapacitytoperceivesomeone’semotionalstatenon-verballybasedonfacialexpressions.
§ ProductionofFacialCommunication:Thecapacitytoconveyone’semotionalstatenon-verballyviafacialexpression.
§ ReceptionofNon-FacialCommunication:Thecapacitytoperceivesocialandemotionalinformationbasedonmodalitiesotherthanfacialexpression,includingnon-verbalgestures,affectiveprosody,distresscalling,cooing,etc.
§ ProductionofNon-FacialCommunication:Thecapacitytoexpresssocialandemotionalinformationbasedonmodalitiesotherthanfacialexpression,includingnon-verbalgestures,affectiveprosody,distresscalling,cooing,etc.
o PerceptionandUnderstandingofSelf:Theprocessesand/orrepresentationsinvolvedinbeingawareof,accessingknowledgeabout,and/ormakingjudgmentsabouttheself.Theseprocesses/representationscanincludecurrentcognitiveoremotionalinternalstates,traits,and/orabilities,eitherinisolationorinrelationshiptoothers,aswellasthemechanismsthatsupportself-awareness,self-monitoring,andself-knowledge.PerceptionandUnderstandingofSelfwasorganizedintothefollowingsub-constructs:
§ Agency:Theabilitytorecognizeone’sselfastheagentofone’sactionsandthoughts,includingtherecognitionofone’sownbody/bodyparts.
§ Self-Knowledge:Theabilitytomakejudgmentsaboutone’scurrentcognitiveoremotionalinternalstates,traits,and/orabilities.
o PerceptionandUnderstandingofOthers:Theprocessesand/orrepresentationsinvolvedinbeingawareof,accessingknowledgeabout,reasoningabout,and/ormakingjudgmentsaboutotheranimateentities,includinginformationaboutcognitiveoremotionalstates,traitsorabilities.PerceptionandUnderstandingofOtherswasorganizedintothefollowingsub-constructs:
§ AnimacyPerception:Theabilitytoappropriatelyperceivethatanotherentityisanagent(i.e.,hasaface,interactscontingently,andexhibitsbiologicalmotion).
§ ActionPerception:Theabilitytoperceivethepurposeofanactionbeingperformedbyananimateentity.
§ UnderstandingMentalStates:Theabilitytomakejudgmentsand/orattributionsaboutthementalstateofotheranimateentitiesthatallowsonetopredictorinterprettheirbehaviors.Mentalstatereferstointentions,beliefs,desires,andemotion
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APPENDIXB:NAMHCROSTER
NationalAdvisoryMentalHealthCouncilDEPARTMENTOFHEALTHANDHUMANSERVICES
NATIONALINSTITUTESOFHEALTHNATIONALINSTITUTEOFMENTALHEALTH
NATIONALADVISORYMENTALHEALTHCOUNCIL(Termsend9/30ofdesignatedyear)
CHAIRPERSONBruceN.Cuthbert,Ph.D.ActingDirectorNationalInstituteofMentalHealthBethesda,MD
EXECUTIVESECRETARYJeanNoronha,Ph.D.DirectorDivisionofExtramuralActivitiesNationalInstituteofMentalHealthBethesda,MD
MembersPatriciaA.Areán,Ph.D.(16)ProfessorDirectorofTargetedTreatmentDevelopmentDepartmentofPsychiatryandBehavioralSciencesUniversityofWashingtonSeattle,WADeannaM.Barch,Ph.D.(16)GregoryB.CouchProfessorofPsychiatryDepartmentofPsychology,PsychiatryandRadiologyWashingtonUniversitySt.Louis,MODavidA.Brent,M.D.(17)AcademicChiefChild&AdolescentPsychiatryEndowedChairinSuicideStudiesProfessorofPsychiatry,PediatricsandEpidemiologyDirector,ServicesforTeensatRiskUniversityofPittsburghSchoolofMedicinePittsburgh,PABJCasey,Ph.D.(16)SacklerProfessorDepartmentofPsychiatryandNeuroscienceSacklerInstituteforDevelopmentalPsychobiologyWeillMedicalCollegeofCornellUniversityNewYork,NYBenjaminG.Druss,M.D.,M.P.H.(18)RosalynnCarterChairinMentalHealthandProfessorDepartmentofHealthPolicyandManagementRollinsSchoolofPublicHealthEmoryUniversityAtlanta,GAHakonHeimer,M.S.(16)FoundingEditorSchizophreniaResearchForumBrainandBehaviorResearchFoundationProvidence,RI
MichaelF.Hogan,Ph.D.(18)ConsultantandAdvisorHoganHealthSolutionsLLCDelmar,NYRichardL.Huganir,Ph.D.(17)ProfessorandDirectorDepartmentofNeuroscienceInvestigator,HowardHughesMedicalInstituteCo-Director,BrainScienceInstituteTheJohnsHopkinsUniversitySchoolofMedicineBaltimore,MDJohnH.Krystal,M.D.(19)RobertL.McNeil,Jr.ProfessorofTranslationalResearchChair,ProfessorofNeurobiologyChiefofPsychiatry,Yale-NewHavenHospitalDepartmentofPsychiatryYaleUniversitySchoolofMedicineNewHaven,CTMarshaM.Linehan,Ph.D.(17)ProfessorandDirectorBehavioralResearchandTherapyClinicsDepartmentofPsychologyUniversityofWashingtonSeattle,WAMariaA.Oquendo,M.D.(17)ViceChairforEducationProfessorofPsychiatryDepartmentofPsychiatryColumbiaUniversityNewYorkStatePsychiatricInstituteNewYork,NY
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GeneE.Robinson,Ph.D.(16)Director,CarlR.WoeseInstituteforGenomicBiologySwanlundChairCenterforAdvancedStudyProfessorinEntomologyAndNeuroscienceUniversityofIllinoisatUrbana-ChampaignUrbana,ILRhondaRobinsonBeale,M.D.(19)SeniorVicePresidentandChiefMedicalOfficerBlueCrossofIdahoMeridian,IDMaryJaneRotheram,Ph.D.(16)Bat-YaacovProfessorofChildPsychiatryAndBehavioralSciencesDirector,GlobalCenterforChildrenandFamiliesDirector,CenterforHIVIdentificationPreventionAndTreatmentServices(CHIPTS)SemelInstituteandtheDepartmentofPsychiatry,UniversityofCalifornia,LosAngelesLosAngeles,CA
J.DavidSweatt,Ph.D.(16)ProfessorandChairmanDepartmentofPharmacologyVanderbiltUniversityNashville,TNHyongUn,M.D.(17)HeadofEAP&ChiefPsychiatricOfficerAETNABlueBell,PAChristopherA.Walsh,M.D.(19)Chief,DivisionofGeneticsandGenomicsBostonChildren’sHospitalBullardProfessorofPediatricsandNeurologyHarvardMedicalSchoolBoston,MA
EXOFFICIOMEMBERSOfficeoftheSecretary,DHHSSylviaM.BurwellSecretaryDepartmentofHealthandHumanServicesWashington,DCNationalInstitutesofHealthFrancisCollins,M.D.,Ph.D.DirectorNationalInstitutesofHealthBethesda,MD
DepartmentofVeteransAffairsTheresaGleason,Ph.D.Deputy,ChiefResearch&DevelopmentOfficerOfficeofResearch&DevelopmentDepartmentofVeteransAffairsWashingtonDCDepartmentofDefenseJohnW.Davison,M.B.A.,Ph.D.Chief,Conditioned-BasedSpecialtyCareSectionClinicalSupportDivisionDefenseHealthAgencyDepartmentofDefenseOfficeoftheChiefMedicalOfficer(OCMO)TRICAREManagementActivity,OASD(HA)FallsChurch,VALiaisonRepresentativePaolodelVecchio,M.S.W.DirectorCenterforMentalHealthServicesRockville,MD
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APPENDIXC:WORKGROUPROSTER
WorkgroupCo-ChairsDeannaM.Barch,Ph.D.,Co-Chair,WashingtonUniversityMariaOquendo,M.D.,Co-Chair,ColumbiaUniversityNAMCHMembersPatriciaAreán,Ph.D.,UniversityofWashingtonDavidBrent,M.D.,UniversityofPittsburghSchoolofMedicineWorkgroupMembersArousalandRegulatorySystemsDaraManoach,Ph.D.,Chair,HarvardMedicalSchool,MassachusettsGeneralHospitalTheodoreBeauchaine,Ph.D.,OhioStateUniversityRuthBenca,M.D.,Ph.D.,UniversityofWisconsin-MadisonAndrewKrystal,M.D.,DukeUniversityCognitiveSystemsCameronCarter,M.D.,Chair,UniversityofCalifornia,DavisNealCohen,Ph.D.,UniversityofIllinoisatUrbana-ChampaignJordanDeVylder,Ph.D.,UniversityofMarylandDwightDickinson,Ph.D.,J.D.,NationalInstituteofMentalHealthDamienFair,Ph.D.,PA-C,OregonHealthSciencesUniversityMartaKutas,Ph.D.,UniversityofCalifornia,SanDiegoSoheePark,Ph.D.,VanderbiltUniversityLucinaUddin,Ph.D.,UniversityofMiamiNegativeValenceSystemsStewartShankman,Ph.D.,Chair,UniversityofIllinoisatChicagoMariadelasMercedesPerez-Rodriguez,M.D.,Ph.D.,MountSinaiSchoolofMedicineEmilyDurbin,Ph.D.,MichiganStateUniversityIanGotlib,Ph.D.,StanfordUniversitySheriJohnson,Ph.D.,UniversityofCalifornia,BerkeleyPositiveValenceSystemsDiegoPizzagalli,Ph.D.,Chair,McLeanHospital/HarvardMedicalSchoolMauricioDelgado,Ph.D.,RutgersUniversityPaulGlimcher,Ph.D.,NewYorkUniversityGregHajcak,Ph.D.,StonyBrookUniversityMichaelTreadway,Ph.D.,EmoryUniversityBenYerys,Ph.D.,Children’sHospitalofPhiladelphia
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SystemsforSocialProcessesKevinPelphrey,Ph.D.,Chair,GeorgeWashingtonUniversityJedElison,Ph.D.,UniversityofMinnesotaWilliamP.Horan,Ph.D.,UniversityofCalifornia,LosAngelesJamesMorris,Ph.D.,UniversityofVirginiaLynnPaul,Ph.D.,CaliforniaInstituteofTechnologyNIMHRDoCUnitBruceCuthbert,PhD.,ActingDirectoroftheInstituteSarahMorris,Ph.D.,ActingDirectoroftheRDoCUnitDedeGreenstein,Ph.D.,NIMHRDocUnitArinaKadam,MPH.,NIMHRDoCUnitJenniPacheco,Ph.D.,NIMHRDoCUnitUmaVaidyanathan,Ph.D.,NIMHRDoCUnit
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APPENDIXD:WORKGROUPAGENDA
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