behavioral assessment methods for rdoc constructs€¦ · a report by the national advisory mental...

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

BehavioralAssessmentMethodsforRDoCConstructs

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

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

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.

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?

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

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

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”.

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

NegativeValenceSystemsRecommendedSelfReportMeasures

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

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.

PositiveValenceSystemsRecommendedTaskParadigms

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

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.

CognitiveSystemsRecommendedTaskParadigms

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

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

SystemsforSocialProcesses(SeeSectionIIforfullreport)TheSystemsforSocialProcessessubgroupsuggestedsomechangestothedomain’sorganization,andsuggestedadding“RejectionSensitivity”and“SocialMotivation”assubconstructsundertheAffiliationandAttachmentconstruct.Thegroupnotedthatthe“SocialCommunication–ProductionofFacialCommunication”subconstructwouldbenefitfromfurtherdevelopmentregardingmethodsofelicitingemotionsandmeasuringfacialexpressions.Beyondfacialcommunication,thereisasignificantneedtodeveloptechniquesandinstrumentsthatcapturethedimensionalityoffunctioningacrossthelifespan,aswellasinstrumentsthatmaximizeecologicalvalidity.

ThedomainsubgroupstronglyrecommendedeliminatingtheStrangeFaces(separation-reunion)task,theStillFace,andtheFordCorollaryDischargeparadigmsfromthelistofparadigmscurrentlylistedintheRDoCmatrix.Thegroupidentifiedsignificantproblemswiththesetasks;howeverthisdoesnotmeantheyendorsealloftheremainingtasksinthecurrentmatrix.

SystemsforSocialProcessesRecommendedTaskParadigms

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

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

SystemsforSocialProcessesRecommendedSelfReportMeasures

1.AffiliationandAttachment

1.2SocialMotivation MultidimensionalScaleofPerceivedSocialSupport

Zimetetal.1988

2.SocialCommunication

2.3.Non-facialcommunication(mergedreceptionandproduction)

SocialResponsivenessScale Constantinoetal.2003

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.

ArousalandRegulatorySystemsRecommendedTasks

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

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.

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.

SECTIONII:DOMAINSPECIFICREPORTS

Thefollowingreportsweregeneratedbyeachdomainsubgroup,basedontheirdiscussionsbothatthemeeting,andafterthemeetingwascomplete.

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.

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

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

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.

doi:10.1006/nimg.2002.1179.2. KirschbaumC,PirkeKM,HellhammerDH.The“TrierSocialStressTest”–AToolfor

InvestigatingPsychobiologicalStressResponsesinaLaboratorySetting.Neuropsychobiology.1993;28(1-2):76-81.doi:10.1159/000119004.

3. AllenAP,KennedyPJ,CryanJF,DinanTG,ClarkeG.Biologicalandpsychologicalmarkersofstressinhumans:FocusontheTrierSocialStressTest.Neuroscience&BiobehavioralReviews.2014;38:94-124.doi:10.1016/j.neubiorev.2013.11.005.

4. EdelsonJT,RobertsonGL.Theeffectofthecoldpressortestonvasopressinsecretioninman.Psychoneuroendocrinology.1986;11(3):307-316.doi:10.1016/0306-4530(86)90016-8.

5. VelascoM,GómezJ,BlancoM,RodriguezI.Thecoldpressortest:pharmacologicalandtherapeuticaspects.Americanjournaloftherapeutics.1997;4(1):34-38.

6. RolkeR,BaronR,MaierC,etal.QuantitativesensorytestingintheGermanResearchNetworkonNeuropathicPain(DFNS):Standardizedprotocolandreferencevalues.Pain.2006;123(3):231-243.doi:10.1016/j.pain.2006.01.041.

7. GormanJM,PappLA,CoplanJD,etal.AnxiogeniceffectsofCO2andhyperventilationinpatientswithpanicdisorder.AmericanJournalofPsychiatry.April1994.doi:10.1176/ajp.151.4.547.

8. PomaSZ,MilleriS,SquassanteL,etal.Characterizationofa7%carbondioxide(CO2)inhalationparadigmtoevokeanxietysymptomsinhealthysubjects.JournalofPsychopharmacology.2005;19(5):494-503.doi:10.1177/0269881105056533.

9. BussKA,SchumacherJRM,DolskiI,KalinNH,GoldsmithHH,DavidsonRJ.Rightfrontalbrainactivity,cortisol,andwithdrawalbehaviorin6-month-oldinfants.BehavioralNeuroscience.2003;117(1):11.doi:10.1037/0735-7044.117.1.11.

10. PfeiferM,GoldsmithHH,DavidsonRJ,RickmanM.ContinuityandChangeinInhibitedandUninhibitedChildren.ChildDevelopment.2002;73(5):1474-1485.doi:10.1111/1467-8624.00484.

11. NorrholmSD,VervlietB,JovanovicT,etal.Timingofextinctionrelativetoacquisition:Aparametricanalysisoffearextinctioninhumans.BehavioralNeuroscience.2008;122(5):1016.doi:10.1037/a0012604.

12. ZeidanMA,LebronMiladK,ThompsonHollandsJ,etal.Test–RetestReliabilityduringFearAcquisitionandFearExtinctioninHumans.CNSNeuroscience&Therapeutics.2012;18(4):313-317.doi:10.1111/j.1755-5949.2011.00238.x.

13. SchmitzA,GrillonC.Assessingfearandanxietyinhumansusingthethreatofpredictableandunpredictableaversiveevents(theNPU-threattest).NatureProtocols.2012;7(3):527-532.doi:10.1038/nprot.2012.001.

14. SamsonAC,KreibigSD,SoderstromB,WadeAA,GrossJJ.Elicitingpositive,negativeandmixedemotionalstates:Afilmlibraryforaffectivescientists.Cognition&Emotion.May2015.doi:10.1080/02699931.2015.1031089.

15. JoormannJ,TalbotL,GotlibIH.Biasedprocessingofemotionalinformationingirlsatriskfordepression.JournalofAbnormalPsychology.2007;116(1):135.doi:10.1037/0021-843X.116.1.135.

16. CherekDR.Effectsofsmokingdifferentdosesofnicotineonhumanaggressivebehavior.Psychopharmacology.1981;75(4):339-345.doi:10.1007/BF00435849.

17. GenioleSN,MacDonellET,McCormickCM.ThePointSubtractionAggressionParadigmasalaboratorytoolforinvestigatingtheneuroendocrinologyofaggressionandcompetition.HormonesandBehavior.April2016.doi:10.1016/j.yhbeh.2016.04.006.

18. GagneJR,VanHulleCA,AksanN,EssexMJ,GoldsmithHH.Derivingchildhoodtemperamentmeasuresfromemotion-elicitingbehavioralepisodes:Scaleconstructionandinitialvalidation.PsychologicalAssessment.2011;23(2):337.doi:10.1037/a0021746.

19. WolpeJ.ThePracticeofBehaviorTherapy.Allyn&Bacon;1990.20. KaplanDM,SmithT,CoonsJ.Avaliditystudyofthesubjectiveunitofdiscomfort(SUD)

score.MeasurementandEvaluationinCounselingandDevelopment.January1995.21. WolpeJ,LangP.Wolpe:ManualfortheFearSurveySchedule.SanDiego,CA:Educational

andIndustrialTestingService;1977.22. CarletonRN,NortonMAPJ,AsmundsonGJG.Fearingtheunknown:Ashortversionofthe

IntoleranceofUncertaintyScale.JournalofAnxietyDisorders.2007;21(1):105-117.doi:10.1016/j.janxdis.2006.03.014.

23. CarverCS,WhiteTL.Behavioralinhibition,behavioralactivation,andaffectiveresponsestoimpendingrewardandpunishment:TheBIS/BASScales.JournalofPersonalityandSocialPsychology.1994;67(2):319.doi:10.1037/0022-3514.67.2.319.

24. WatsonD,FriendR.Measurementofsocial-evaluativeanxiety.1969.doi:10.1111/j.2044-8341.1967.tb00577.x/abstract.

25. TaylorS,ZvolenskyMJ,CoxBJ,etal.Robustdimensionsofanxietysensitivity:DevelopmentandinitialvalidationoftheAnxietySensitivityIndex-3.PsychologicalAssessment.2007;19(2):176.doi:10.1037/1040-3590.19.2.176.

26. BrownGW,HarrisT.Socialoriginsofdepression:areply.PsychologicalMedicine.1978;8(04):577-588.doi:10.1017/S0033291700018791.

27. RUDOLPHKD,FLYNNM.Childhoodadversityandyouthdepression:Influenceofgenderandpubertalstatus.DevelopmentandPsychopathology.2007;19(02):497-521.doi:10.1017/S0954579407070241.

28. BernsteinDP,FinkL.Bernstein:ChildhoodTraumaQuestionnaire:aRetrospectiv...-GoogleScholar.1998.

29. IppenCG,FordJ,RacusinR,etal.TraumaticEventsScreeningInventory-ParentReportRevised.2002.

30. TaylorSE,LernerJS,SageRM,LehmanBJ,SeemanTE.EarlyEnvironment,Emotions,ResponsestoStress,andHealth.JournalofPersonality.2004;72(6):1365-1394.doi:10.1111/j.1467-6494.2004.00300.x.

31. SlavichGM,EpelES.TheStressandAdversityInventory(STRAIN):Anautomatedsystemforassessingcumulativestressexposure.LosAngeles:UniversityofCalifornia.2010.

32. WrightKA,LamDH,BrownRG.Reducedapproachmotivationfollowingnonreward:ExtensionoftheBIS/BASscales.PersonalityandIndividualDifferences.2009;47(7):753-757.doi:10.1016/j.paid.2009.06.015.

33. BaarsMY,252M,llerMJ,etal.DepressiveandAggressiveResponsestoFrustration:DevelopmentofaQuestionnaireandItsValidationinaSampleofMaleAlcoholics.DepressionResearchandTreatment.2011;2011.doi:10.1155/2011/352048.

AppendixNVS-I:NVSdomaingrouptableontaskcriteriaforrecommendedparadigms NVS

Construct

ValidM

easureof

Construct(#1

Test-Retest

Reliability(#2)

iling(#

PracticeEffects(#2

Longitu

lStability

dardize

dParameters(#4

Copyrig

Canitbe

usedacross

ysites?(#9)

Canitbe

usedwith

childrenorsp

ns?(#6)

Sensitivityto

nge(#10

Tolerability(#18

Acutethreat TrierSocialStressTest

4 *3* *3* ? ? 2 5 5 Ages:5

Culture:4?

Acutethreat BehavioralapproachTest

4 ? ? N/A ? 2 5 5 Ages:5

Culture:4

Acutethreat Coldpressorandotherpaintolerancetasks

4 3 ? ? 3 4(butnotalwaysattendedtoinliterature)

5 3 Ages:5

Culture:5

Acutethreat CO2challenge 4 3 ? 4 5 5 Ages:5

Culture:4

Acutethreat Strangertasks 4 ? 5 1 3 2 5 5 Ages:5

Culture:5

Acutethreat(learning)

Fearconditioning

5 2 ? ? ? 4 5 5 Ages:5

Cultures:

Potentialthreat

NPUThreat-Task

4/5 4 5 ? ? 2 5 3 Ages:5

Culture:3

Loss Sadnesselicitingfilmclips(seecaveatsabove)

4 ? ? ? ? 3 3(somemaybecopyrighted)

5 Ages:5

Culture:4

Frustrativenonreward

LabTAB:BoxEmpty,TransparentBox

5 4 5 ? 4(onlyifmult.tasksareused)

2 5 3 5,Adults(potentiallyadaptable)

Culture:?

4 1* 1* ? 1? 1 5 3 1

Couldbeadapted

struct(resto

fcrite

(resto

fcriteria)

Alternateform

Internalre

liability(#2)

usedinclinical

trialsorsc

ing(#5)

havioralta

sk?(#7)

Canusewith

imaging

Relatb

skperf&

uralsigknow

Clinicalphe

notype

Measureso

constructo

?(#16)

Anytaskth

Norms(#8

Acutethreat TrierSocialStressTest

1 ?? 1 5 4* 2 5 4 -- 1 1

Threat Behavioralapproach

1 ? 4 5 5 5 5 5 Lotsofmodifications

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

Acutethreat(learning)

Fearconditioning

5 4 5 5 4 5 4 Many N/A 5

Potentialthreat

NPU 4 3(withSUDSratings)

5 5 5 5 -- 1 5

Loss Sadnesselicitingfilmclips,espw/immersion;facialexpormoodratings

4 ? 4 5 5 3 4 2/3 Yes,many 3 1

1 ? 4 5 5 3 4 3(constructitselfisbroad.Measuretapslossaswellasthreat)

Couldbemodifiedforchildren

LabTAB:BoxEmpty,TransparentBox

1 4 3 5 2 -- 3 3(constructitselfisbroad.Measuretapscognitivecontrolandpositiveemotionality)

Couldbemodifiedforadults

AppendixNVS-II:NVSdomaingrouptableontaskcriteriaforparadigmsthatneedmorework,ratedfrom1(noevidence)-5(strongevidence)

Construct

ValidM

easureof

Construct(#1)

Test-Retest

Reliability(#2)

iling(#

PracticeEffects

Longitu

Stability(#

Standardize

dParameters(#4)

Copyrig

Canitbe

acrossm

anysites?

Canitbe

rspecial

ns?(#6)

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

Construct(rest

ofcriteria)

(resto

fcrite

Alternate

Internal

reliability(#2)

usedin

clinicaltrials

Standalon

havioral

task?(#7)

Canusewith

agingor

ERP?(#

Relatb

perf&neu

sigkno

Clinical

Measureso

constructo

rspecificto

one?(#

Anytaskth

couldbe

?(#17)

Norms(#8)

analogue

VigilanceorAttentionalcapture

DotProbe(supraliminal1000mspresentationofangry/fearfulfaces)

2 1 4 5 5 4 5 3 -- 1 3

Inabilitytodisengagefromnegativestimulus

ExogenousCuingTask

2 ? 4 5 3 ? 3 3 Lotsofmodif.arepossible

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.

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

1.2.RewardAnticipation

1.3.RewardSatiation

2.RewardLearning

2.1.Habit

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.

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.

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

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.

TABLE2:RecommendedTasksforeachPVSsub-constructConstruct/Sub-construct Task Keyreferences

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

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

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

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

MonetaryIncentiveDelayTask2:TheMIDwasrecommendedforthesub-construct“RewardAnticipation”(seeSectionIII,Point1.2.)butnotforthesub-construct“InitialResponsivenesstoReward”duetopoorvalidityindissociatingpredictionerrorandoutcomevaluesignals.Specifically,formalmodelingexpectationofrewardoutcomeinthistaskischallenging,asitwillbeinfluencedbybothoutcomesofpriortrialsaswellasperformanceonthecurrenttrial(e.g.,dependingonRTtothetarget,participantshaveagoodexpectationoftheupcomingoutcome).Moreover,commonattemptstoworkaroundthislimitationbymodelingexpectationasjusttheaveragerewardrateresultinpredictionerrorvaluesthatareco-linearwithoutcomevalues.

CueReactivityTasks:Notconsideredbecausethesetaskslikelyengagerewardanticipationinsomeconditions,butinitialresponsivenesstorewardinothers.

1.3.RewardSatiation

DevaluationTasks:Poorconstructvalidityforthissub-construct—likelyamuchbettermeasureofhabit.

2.RewardLearning

2.1.Habit

KnotTyingandSerialResponseTasks:notdiscussedbecausetheymostlyprobeprocedurallearning;similarly,AttentionalBlindnessTaskswerenotconsideredbecausetheyassessattentionalbiasrelatedtoexpertise.

DriftingBandit14:Excellentproperties;ithasbeenusedinstudiesinParkinsonanddopaminergicchallenges;itcanmeasureexploration/exploitationandallowstofitlearningrateandbias.Itwasnotdiscussedfurther,however,becauseDoubleBanditTasks(e.g.,Dawetal.2011)yieldthesameoutcomevariablesandallowonetoparsebothmodel-basedandmodel-freeparametersinthesametask,andarethusmoreefficient.

PavlovianInstrumentalTransferTasks35:interestingtaskbutitrequiresworkbeforewidedisseminationbecause~30%ofparticipantsareunabletolearnit).

3.RewardValuation

3.2.Delay

3.3.Effort

ProgressiveRatioTask36:Inspiteoftheirwidespreaduseintheliterature,ProgressiveRatioTaskswerenotconsideredbecausetheyconfoundeffort,timediscounting,rewardmagnitude(andsatiety).

VI.References1. BecharaA,DamasioH,TranelD,DamasioAR.DecidingAdvantageouslyBeforeKnowing

theAdvantageousStrategy.Science.1997;275(5304):1293-1295.doi:10.1126/science.275.5304.1293.

2. KnutsonB,WestdorpA,KaiserE,HommerD.FMRIVisualizationofBrainActivityduringaMonetaryIncentiveDelayTask.NeuroImage.2000;12(1):20-27.doi:10.1006/nimg.2000.0593.

3. DelgadoMR,NystromLE,FissellC,NollDC,FiezJA.TrackingtheHemodynamicResponsestoRewardandPunishmentintheStriatum.JournalofNeurophysiology.2000;84(6):3072-3077.doi:10.1016/0166-2236(90)90107-L.

4. CarlsonJM,FotiD,Mujica-ParodiLR,Harmon-JonesE,HajcakG.VentralstriatalandmedialprefrontalBOLDactivationiscorrelatedwithreward-relatedelectrocorticalactivity:AcombinedERPandfMRIstudy.NeuroImage.2011;57(4):1608-1616.doi:10.1016/j.neuroimage.2011.05.037.

5. ShermanJA,ThomasJR.SomeFactorsControllingPreferenceBetweenFixed-RatioandVariable-RatioSchedulesofReinforcement.JournaloftheExperimentalAnalysisofBehavior.1968;11(6):689–&.

6. GottfriedJA,O'DohertyJ,DolanRJ.EncodingPredictiveRewardValueinHumanAmygdalaandOrbitofrontalCortex.Science.2003;301(5636):1104-1107.doi:10.1126/science.1087919.

7. BalleineB,DickinsonA.Signallingandincentiveprocessesininstrumentalreinforcerdevaluation.TheQuarterlyJournalofExperimentalPsychology.May2007.doi:10.1080/14640749208401007.

8. McKimTH,BauerDJ,BoettigerCA.Addictionhistoryassociateswiththepropensitytoformhabits.JournalofCognitiveNeuroscience.2016;28(7):1024-1038.

doi:10.1162/jocn_a_00953.9. TricomiE,BalleineBW,O'DohertyJP.Aspecificroleforposteriordorsolateralstriatumin

humanhabitlearning.EuropeanJournalofNeuroscience.2009;29(11):2225-2232.doi:10.1111/j.1460-9568.2009.06796.x.

10. PizzagalliDA,JahnAL,O’SheaJP.Towardanobjectivecharacterizationofananhedonicphenotype:Asignal-detectionapproach.BiologicalPsychiatry.2005;57(4):319-327.doi:10.1016/j.biopsych.2004.11.026.

11. O'DohertyJ,DayanP,SchultzJ,DeichmannR,FristonK,DolanRJ.DissociableRolesofVentralandDorsalStriatuminInstrumentalConditioning.Science.2004;304(5669):452-454.doi:10.1126/science.1094285.

12. FrankMJ,SeebergerLC,O'ReillyRC.ByCarrotorbyStick:CognitiveReinforcementLearninginParkinsonism.Science.2004;306(5703):1940-1943.doi:10.1126/science.1102941.

13. DawND,GershmanSJ,SeymourB,DayanP,DolanRJ.Model-BasedInfluencesonHumans'ChoicesandStriatalPredictionErrors.Neuron.2011;69(6):1204-1215.doi:10.1016/j.neuron.2011.02.027.

14. RutledgeRB,DeanM,CaplinA,GlimcherPW.Testingtherewardpredictionerrorhypothesiswithanaxiomaticmodel.JournalofNeuroscience.2010;30(40):13525-13536.doi:10.1523/JNEUROSCI.1747-10.2010.

15. LevyI,SnellJ,NelsonAJ,RustichiniA,GlimcherPW.NeuralRepresentationofSubjectiveValueUnderRiskandAmbiguity.JournalofNeurophysiology.2010;103(2):1036-1047.doi:10.1152/jn.00853.2009.

16. HoltCA,LaurySK.Riskaversionandincentiveeffects.Americaneconomicreview.2002.17. BeckerGM,DegrootMH,MarschakJ.Stochasticmodelsofchoicebehavior.Behavioral

Science.1963;8(1):41-55.doi:10.1002/bs.3830080106.18. LouieK,KhawMW,GlimcherPW.Normalizationisageneralneuralmechanismfor

context-dependentdecisionmaking.PNAS.2013;110(15):6139-6144.doi:10.1073/pnas.1217854110.

19. KableJW,GlimcherPW.Theneuralcorrelatesofsubjectivevalueduringintertemporalchoice.Natureneuroscience.2007;10(12):1625-1633.doi:10.1038/nn2007.

20. BickelWK,MarschLA.Towardabehavioraleconomicunderstandingofdrugdependence:delaydiscountingprocesses.Addiction.2001;96(1):73-86.doi:10.1046/j.1360-0443.2001.961736.x.

21. JohnsonMW,BickelWK.WITHIN-SUBJECTCOMPARISONOFREALANDHYPOTHETICALMONEYREWARDSINDELAYDISCOUNTING.JournaloftheExperimentalAnalysisofBehavior.2002;77(2):129-146.doi:10.1901/jeab.2002.77-129.

22. GreenL,MyersonJ.ADiscountingFrameworkforChoiceWithDelayedandProbabilisticRewards.PsychologicalBulletin.2004;130(5):769.doi:10.1037/0033-2909.130.5.769.

23. TreadwayMT,BuckholtzJW,SchwartzmanAN,LambertWE,ZaldDH.Worththe“EEfRT?”Theeffortexpenditureforrewardstaskasanobjectivemeasureofmotivationandanhedonia.PLOSONE.2009;4(8):e6598.doi:10.1371/journal.pone.0006598.

24. ReddyLF,HoranWP,BarchDM,etal.Effort-BasedDecision-MakingParadigmsforClinicalTrialsinSchizophrenia:Part1—PsychometricCharacteristicsof5Paradigms.SchizophrBull.2015;41(5):sbv089-sbv1054.doi:10.1093/schbul/sbv089.

25. KoolW,McGuireJT,RosenZB,BotvinickMM.Decisionmakingandtheavoidanceofcognitivedemand.JournalofExperimentalPsychology:General.2010;139(4):665.doi:10.1037/a0020198.

26. YoungJW,MarkouA.TranslationalRodentParadigmstoInvestigateNeuromechanismsUnderlyingBehaviorsRelevanttoAmotivationandAlteredRewardProcessinginSchizophrenia.SchizophrBull.2015;41(5):1024-1034.doi:10.1093/schbul/sbv093.

27. WestbrookA,KesterD,BraverTS.WhatIstheSubjectiveCostofCognitiveEffort?Load,Trait,andAgingEffectsRevealedbyEconomicPreference.PLOSONE.2013;8(7):e68210.doi:10.1371/journal.pone.0068210.

28. CulbrethA,WestbrookA,BarchD.Negativesymptomsareassociatedwithanincreasedsubjectivecostofcognitiveeffort.JournalofAbnormalPsychology.2016;125(4):528.doi:10.1037/abn0000153.

29. LibedinskyC,MassarS,LingA,CheeW,HuettelSA.Sleepdeprivationalterseffortdiscountingbutnotdelaydiscountingofmonetaryrewards.Sleep.2013.

30. CockerPJ,HoskingJG,BenoitJ,WinstanleyCA.SensitivitytoCognitiveEffortMediatesPsychostimulantEffectsonaNovelRodentCost|[sol]|BenefitDecision-MakingTask.Neuropsychopharmacology.2012;37(8):1825-1837.doi:10.1038/npp.2012.30.

31. Cléry-MelinM-L,SchmidtL,LafargueG,BaupN,FossatiP,PessiglioneM.WhyDon'tYouTryHarder?AnInvestigationofEffortProductioninMajorDepression.PLOSONE.2011;6(8):e23178.doi:10.1371/journal.pone.0023178.

32. SchmidtL,LebretonM,Cléry-MelinM-L,DaunizeauJ,PessiglioneM.Neuralmechanismsunderlyingmotivationofmentalversusphysicaleffort.PLoSBiology.2012;10(2):e1001266.doi:10.1371/journal.pbio.1001266.

33. AharonI,EtcoffN,ArielyD,ChabrisCF,O'ConnorE,BreiterHC.BeautifulFacesHaveVariableRewardValue.Neuron.2001;32(3):537-551.doi:10.1016/S0896-6273(01)00491-3.

34. CascioCJ,FossFeigJH,HeacockJ,etal.Affectiveneuralresponsetorestrictedinterestsinautismspectrumdisorders.JournalofChildPsychologyandPsychiatry.2014;55(2):162-171.doi:10.1111/jcpp.12147.

35. CorbitLH,BalleineBW.DoubleDissociationofBasolateralandCentralAmygdalaLesionsontheGeneralandOutcome-SpecificFormsofPavlovian-InstrumentalTransfer.JNeurosci.2005;25(4):962-970.doi:10.1523/JNEUROSCI.4507-04.2005.

36. HodosW,KalmanG.EFFECTSOFINCREMENTSIZEANDREINFORCERVOLUMEONPROGRESSIVERATIOPERFORMANCE.JournaloftheExperimentalAnalysisofBehavior.1963;6(3):387-392.doi:10.1901/jeab.1963.6-387.

Appendix1:Ratingsoftasksrecommendedforconsideration.

DOMAIN:POSITIVEVALENCESYSTEMS

Criteria(Rateeachonascaleof1-5,with1=doesnotdoagoodjobofmeetingthecriterion;5=doesanexcellentjobmeetingthecriterion

Construct Task

ValidM

easureof

Construct

Test-Retest

Reliability

PracticeEffects

Longitud

Sensitivetow/in

person

dardized

Parameters

Canitbeused

acrosssites?

Canitbeused

kidsorspecial

lation

Arenormativeda

available?

Arerelationsto

clinicalfe

atures

Notcop

yrighted

SimpleGuessingTask(e.g.50%CardTask)

57 3 5 5 4 5 3 5 48 1 4 5

7Butnobehavioraloutcomeavailable.Itwouldrequiretheadditionofself-reportorpsychophysiologicalassessments.8Withchildrenthan7yearsold

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

a)ProbabilisticRewardTask

b)PavlovianConditioning

c)Driftingdoublebandit

d)ProbabilisticStimulusSelectionTask

a)RutledgePassiveLotteryTask

b)DriftingDoubleBandit(seeabove)

1(u)f1(u)f

9Forbehavioraloutcome10Forneuraloutcome11GoodbutlowN12Unknown13Children,OCD,autism14Freelyavailableforresearchers/non-profits;usebyindustryrequireslicensing

3.RewardValuation

ProbabilityChoiceTask

WillingnessToPayTask

1(u)f1(u)f

3.2.Delay DelayedDiscountingTask

3.3.Effort EffortExpenditureforRewardTask 415 3 5 4 4 5 3 5 4 2 4 4h

15Itmanipulateseffortsandtimelineatthesametime,thusnotapuremeasureofeffort.Modificationscouldbeapplied.

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

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

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

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.

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.

B.DoorsTask(e.g.,Hajcaketal.)

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.

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.

i. Taskstimuliwereoptimizedtobesimpleandcanbeusedwithalargeagerange(aslowas4yearsinongoingwork);althoughthetaskproducesinternallyreliablereward-relatedneuralmeasureswith40-60trials,itappearsthathalfasmanytrialsmayberequired15—thoughwhethertasklengthimpactsrelationshipswithindividualdifferencesisunknown.

rangeofimpairment?

i. Yes;taskhasbeenusedwithchildrenandotherspecialpopulations.

i. InadditiontotheU.S.,thetaskhasbeenusedinAsiansamples,wherereward-relatedneuralactivityhasalsobeenrelatedtodepressionandanhedonia14.

ii. Thereisnoapriorireasontobelievethatitwouldperforminaculturally-specificway.

i. Yes,asevidencedbyfindingsinpatientsamples(seeabove).

i. Intheory,yes;thoughananimalversionhasnotbeencreated.

i. Yes,publisheddatain9year-olds12;ongoingworkin3-6yearolds.

i. Yes;thetaskhasbeenusedtoexaminereward-relatedbrainactivityusingbothEEGandfMRI.

i. RewardPositivity(inERP),orthedifferencebetweenrewardandnon-reward(i.e.,averageactivityfrom250-350msfollowingfeedbackatFCz;thisappearslateramongyoungersubjects)

ii. Reward-circuitactivationusingfMRI(i.e.,striatalresponse,medialprefrontalcortexresponse)

i. Thetaskhasbeenadministeredtomorethan1,000individuals.Age-andgender-relatednormsarenotavailable,butcouldbecreated.

i. Thetaskassessesinitialresponsivenesstoreward,operationalizedintermsofneuralresponse.Behaviorally,itispossibletoexaminewin-stay/lose-shiftstrategies,thoughthesedatahaverelatedinconsistentlytoneuralresponsetorewards.

i. Neuralresponsetorewardonthedoorstaskhasbeenrelatedtodepressionandrelatedconstructs—bothcross-sectionallyandprospectively.

i. Yes;itiscurrentlybeingusedatmanyresearchsites.

15. Canthetaskbeusedasastand-alonebehavioraltask?i. No

i. Examineimpactofpharmacologicalchallengeii. Animalmodeloftaskiii. Examinewhethermeasuresaresensitivetotreatmentresponse

17. Isthetaskcopyrighted?

i. No.

References

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.

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

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).

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).

v.Alternateforms(i.e.,pseudorandomorders)areavailableandproduceindistinguishableresults.

vi.Developmentalstabilityoveradolescenceiscurrentlybeingassessedinlargesamples(e.g.,IMAGEN).

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.

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.

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)

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).

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.

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(knutson@stanford.edu),whocanproviderecentcopiesofthetaskuponrequest.

References

1. KnutsonB,Westdorpa,KaiserE,HommerD(2000):FMRIvisualizationofbrainactivityduringamonetaryincentivedelaytask.Neuroimage12:20–7.

2. HaberSN,KnutsonB(2010):Therewardcircuit:linkingprimateanatomyandhumanimaging.Neuropsychopharmacology35:4–26.

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.

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.

AppendixPVS-IIc:DetailedEvaluationCriteriaforDevaluationLearningTasks

PVSConstruct:RewardLearning

PVSSub-construct:Habit

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.

i. highinternalreliability:notevaluatedii. test-retestreliability:notevaluatediii. Sensitivity/specificity:notevaluatediv. Limitedpracticeeffects:notevaluatedv. Availabilityofalternateforms:notevaluatedbutpossiblevi. Longitudinalstability:notevaluated

i. No.Parametersneedtobeoptimizedforadministrationacrossadult,pediatric,andclinicalpopulations.

rangeofimpairment?

i. Incomplete;taskcharacteristicsshowadequatevariabilityacrosshealthyadultandadultclinicalpopulations,butadditionalworkisneededforpediatricpopulations.

i. Notyetknown

i. Yes,asevidencedbypsychopharmacologicchallenge(Worbeetal.2015;deWitetal.2012)andfindingsinpatientpopulations(Sjoerdsetal.2013;Gillanetal.2011;Delormeetal.2016).

i. Incomplete–onestudytodateshowseffectiveanimalanalog(Smith&Graybiel2016).

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.

i. Yes(seeabove).ThetaskhasbeenimplementedwithfMRIandDTI(deWitetal.2009;Delormeetal.2016)

i. Differencescoreofvaluableminusdevaluedresponse%inSlips-of-ActionandBaselinephases

ii. Correct/IncorrectresponsesanddecreasesinRToverthecourseofthelearningphaseiii. AccuracyduringtheOutcome-devaluationstage

i. Yes(seeabove).Linkagetostriatuminhumans(Delormeetal.2016;deWitetal.2009)andanimals(Smith&Graybiel2016).

i. Yes,correlateswithticseverityinGillesdelaTouretteSyndrome(Delormeetal.2016)andpoorerdevaluationobservedinpatientswithOCD(Gillanetal.2011)andalcoholdependence(Sjoerdsetal.2013)butnotParkinson’s(deWitetal.2011)orautism(Geurts&deWit2013).

i. Yes

15. Canthetaskbeusedasastand-alonebehavioraltask?i. Yes

i. Optimizationacrosspediatricandclinicalpediatricpopulations,validityandnormalizationanalyses.

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).

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

AppendixPVS-IId:DetailedEvaluationCriteriaforProbabilisticRewardTask

PVSConstruct:RewardLearning

PVSSub-construct:ProbabilisticandReinforcementLearning

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).

(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).

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)

i. Taskcharacteristics(e.g.,stimulussizeandexposure)wereoptimizedinordertoachieveanoverallaccuracy~0.85(toallowconditionorgroupmodulations).

rangeofimpairment?

i. Yes;taskcharacteristics(e.g.,stimulussizeandexposure)wereoptimizedinordertoachieveanoverallaccuracy~0.85.

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.

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).

i. Yes;aconceptuallyanalogousversionhasbeendevelopedforrats(Der-Avakianetal.2013).Cross-speciesstudieshaveshownthatthesamefindingshaveemergedinhumansandratswhenusingpharmacologicalchallenges(Pizzagalli,Evins,etal.2008;Der-Avakianetal.2013),nicotinewithdrawal(Pergadiaetal.2014),orstressors(Bogdan&Pizzagalli2006)(andDer-Avakianetal.,inpreparation).

i. Some(unpublished)datainchildren

i. Yes(seeabove).ThetaskhasbeenusedinconjunctionwithERP,fMRIandPET.

i. Responsebiasii. Rewardlearning(e.g.,RB(block3)–RB(Block1)iii. Secondary:Discriminability,accuracy,RT

i. Thetaskhasbeenadministeredtoover1,000individuals.Age-andgender-relatednormsareavailable.

i. Yes(seepoint#1)

i. Yes(standardizationandamanualhavebeendevelopedfortheEMBARCstudy).ii. Inaddition,Dr.Pizzagalli’slabhasfeelyprovidedthetasktoover110groupssince

2005,andextensivedocumentation/manualsareavailableforstandardizationacrosssites.

15. Canthetaskbeusedasastand-alonebehavioraltask?

i. Yes

i. EMBARCandCNTRACSwillprovideinforegardingitsuseinclinicaltrials

17. Isthetaskcopyrighted?i. Thecodeiscopyrighted(HarvardUniversity)andisprovidedforfreetoacademic

groups.Alicenseagreementisrequiredforindustry.

References:

Seeoverallbibliography

AppendixPVS-IIe:DetailedEvaluationCriteriaforRiskandAmbiguityTask

PVSConstruct:RewardValuation

PVSSub-construct:Reward(probability)

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.

i. highinternalreliability:notevaluatedii. test-retestreliability:riskandambiguityattitudesstablein18subjectsacrosstwo

sessionsseparatedbyseveraldays1,butreliabilitynotquantified.iii. Sensitivity/specificity:notevaluatediv. Limitedpracticeeffects:notevaluatedv. Availabilityofalternateforms:severalversionsofthetaskhavebeenusedvi. Longitudinalstability:notevaluated

rangeofimpairment?

i. Thetaskhasbeenusedinawiderangeofages,includingseveralpsychiatricconditions(seeabove),withnofloor/ceilingeffects.

i. Thetaskisfreefromculture-andlanguage-specificstimuli.Performanceacrossculturesnotevaluated.

i. Notevaluated

i. Inprinciplethetaskisspecifictohumans,asitrequiresunderstandingofsymbolicprobabilities.Onestudy,however,usedananaloginmonkeys10.

i. Yes,thetaskhasbeensuccessfullyusedacrossawiderangeofages,from8to90yearsold3-6.

i. Yes,thetaskhasbeenusedwithfMRI1.

i. Riskandambiguityattitudesinthegainandlossdomains,estimatedbasedonproportionofchoicesofeachtype,orbasedonfittingabehavioralmodel

i. Estimatesofdecisionqualitybasedonviolationsoffirst-orderstochasticdominanceandtransitivity

i. Onlypartially(seeabove)

i. Relationshipswithsomefeatures,includingobsessivecompulsivedisorderandanxiousarousalareknown(seeabove)

i. Yes.Itincludesstandardizedinstructionsandhasbeenusedinamulti-sitestudyatYaleandNYU3,4.Thetaskwasalsoprovideduponrequesttoseveralothergroups.

15. Canthetaskbeusedasastand-alonebehavioraltask?

i. Yes.

i. Standardizationofparameters,estimationoftheminimaltasklengthrequiredforadequateparameterestimates.

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.

9. Gilaie-DotanS,TymulaA,CooperN,KableJW,GlimcherPW,LevyI.Neuroanatomypredictsindividualriskattitudes.JNeurosci.2014;34(37):12394-12401.

10. HaydenBY,HeilbronnerSR,PlattML.Ambiguityaversioninrhesusmacaques.FrontNeurosci.2010;4.

AppendixPVS-IIf:DetailedEvaluationCriteriafortheEffort-ExpenditureforRewardsTask

PVSConstruct:RewardValuation

PVSSub-construct:Effort

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.

i. highinternalreliability:evaluationinprocess;willbeavailableinwinter2016

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)

i. Partially.Taskparametersaresettofacilitatehighcompletionrates(>90%)ofhighandloweffortoptioninhealthyormild/moderatepsychiatricpatients.

rangeofimpairment?

i. Partially.Somesubjectswillmakeallofonechoicetype(i.e.,alleasyorallhardchoices).Thisisestimatedtooccur<5%basedinhealthyparticipants,butmaybemoreprevalentinpatientpopulationswithvaryingimpairments.

i. FindingsintheUS8havebeenreplicatedinanindependently-collectedChinesesample7.

ii. Thetaskhasbeenshared>85researchgroupsacross7countries.Modificationofrewardmagnitudesmaybenecessarytoadjustfordifferencesincurrencyvaluations.

i. Repeated-administrationshaveshownsensitivityofthetasktomanipulationsofdopamine(amphetamine)3andadenosine3.

i. Yes–thetaskwasmodeledafterwell-knowneffort-baseddecision-makingparadigmsinrodents1,15,16

i. Some(unpublished)datahavebeenadministeredinchildren.

i. Yes–publisheddatahavelinkedthetaskoffMRI17,EEG4,18,anddopamine-receptorPETimaging4

i. Totalproportionofhardtaskchoicesii. Differenceinproportionofhardtaskchoicesforhighvs.lowprobabilitylevelsand/or

reward

i. Thetaskhasbeenadministeredinover1,000individuals.Age,Sex,IQandSESnormsareintheprocessofbeingcompiled,andareexpectedtobepublishedinthewinterof2016.

i. Partially–functionalneuroimagingstudiesareinprogress

i. Partially(seepoint#1)

i. Yes

15. Canthetaskbeusedasastand-alonebehavioraltask?i. Yes–mostpublishedpapersusingthetaskhaveuseditasastand-alonetask

i. Thetaskiscurrentlybeingusedinclinicaltrialsforschizophrenia.Preparationforotherpatientgroupsmayberequired.

17. Isthetaskcopyrighted?i. Thetaskiscopyrighted(EmoryUniversityandVanderbiltUniversity)andalicenseis

requiredfornon-academicuse(i.e.,industry).Thetaskismadefreelyavailableforacademicresearch.

References

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.

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.

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.

• 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.

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.

• 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

• 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

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

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.

ConstructWorkingMemory,FlexibleUpdating

• Letternumbersequencingo Well-knownpaperandpenciltaskthathasbeenstandardizedandpsychometrically

refined(e.g.,fortheWAISIQbatteryo Lacksexperimentalrefinementbutmaybeusefultogetanapproximateindexof

thissub-constructthoughnotwithoutcontroversye.g.29

V.References1. CarterCS,RobertsonLC,ChaderjianMR,CelayaLJ,NordahlTE.Attentionalasymmetryin

schizophrenia:controlledandautomaticprocesses.BiologicalPsychiatry.1992;31(9):909-918.doi:10.1016/0006-3223(92)90117-I.

2. MacLeodJW,LawrenceMA,McConnellMM,EskesGA,KleinRM,ShoreDI.AppraisingtheANT:PsychometricandTheoreticalConsiderationsoftheAttentionNetworkTest.Neuropsychology.2010;24(5):637-651.doi:10.1037/a0019803.

3. GoldJM,FullerRL,RobinsonBM,BraunEL,LuckSJ.Impairedtop–downcontrolofvisualsearchinschizophrenia.SchizophreniaResearch.2007;94(1-3):148-155.doi:10.1016/j.schres.2007.04.023.

4. MathisKI,WynnJK,BreitmeyerB,NuechterleinKH,GreenMF.Theattentionalblinkinschizophrenia:Isolatingtheperception/attentioninterface.JournalofPsychiatricResearch.2011;45(10):1346-1351.doi:10.1016/j.jpsychires.2011.04.002.

5. NuechterleinKH,PASHLERHE,SUBOTNIKKL.Translatingbasicattentionalparadigmstoschizophreniaresearch:Reconsideringthenatureofthedeficits.Developmentand

Psychopathology.2006;18(03):831-851.doi:10.1017/S095457940606041X.6. BarchDM,CarterCC,DakinSC,etal.TheClinicalTranslationofaMeasureofGain

Control:TheContrast-ContrastEffectTask.SchizophrBull.November2011:sbr154.doi:10.1093/schbul/sbr154.

7. SmallwoodJ,SchoolerJW.TheScienceofMindWandering:EmpiricallyNavigatingtheStreamofConsciousness.http://dxdoiorg/101146/annurev-psych-010814-015331.January2015.doi:10.1146/annurev-psych-010814-015331.

8. StraussME,McLouthCJ,BarchDM,etal.TemporalStabilityandModeratingEffectsofAgeandSexonCNTRaCSTaskPerformance.SchizophrBull.2014;40(4):835-844.doi:10.1093/schbul/sbt089.

9. SilversteinSM,KeaneBP,BarchDM,etal.OptimizationandValidationofaVisualIntegrationTestforSchizophreniaResearch.SchizophrBull.2011;38(1):sbr141–134.doi:10.1093/schbul/sbr141.

10. RaglandJD,RanganathC,BarchDM,etal.RelationalandItem-SpecificEncoding(RISE):TaskDevelopmentandPsychometricCharacteristics.SchizophrBull.2012;38(1):114-124.doi:10.1093/schbul/sbr146.

11. SheffieldJM,GoldJM,StraussME,etal.Commonandspecificcognitivedeficitsinschizophrenia:relationshipstofunction.CognAffectBehavNeurosci.2014;14(1):161-174.doi:10.3758/s13415-013-0211-5.

12. SchlichtingML,ZeithamovaD,PrestonAR.CA1subfieldcontributionstomemory

integrationandinference.Hippocampus.2014;24(10):1248-1260.doi:10.1002/hipo.22310.

13. BakkerA,KirwanCB,MillerM,StarkCEL.PatternSeparationintheHumanHippocampalCA3andDentateGyrus.Science.2008;319(5870):1640-1642.doi:10.1126/science.1152882.

14. BoucherL,PalmeriTJ,LoganGD,SchallJD.Inhibitorycontrolinmindandbrain:Aninteractiveracemodelofcountermandingsaccades.PsychologicalReview.2007;114(2):376.doi:10.1037/0033-295X.114.2.376.

15. LuijtenM,MachielsenMWJ,VeltmanDJ,HesterR,HaanLde,FrankenIHA.SystematicreviewofERPandfMRIstudiesinvestigatinginhibitorycontrolanderrorprocessinginpeoplewithsubstancedependenceandbehaviouraladdictions.169.2014.doi:10.1503/jpn.130052.

16. Lopez-GarciaP,LeshTA,SaloT,etal.Theneuralcircuitrysupportinggoalmaintenanceduringcognitivecontrol:acomparisonofexpectancyAX-CPTanddotprobeexpectancyparadigms.CognAffectBehavNeurosci.2015;16(1):164-175.doi:10.3758/s13415-015-0384-1.

17. HendersonD,PoppeAB,BarchDM,etal.OptimizationofaGoalMaintenanceTaskforUseinClinicalApplications.SchizophrBull.2012;38(1):104-113.doi:10.1093/schbul/sbr172.

18. SnitzBE,MacDonaldAIII,CohenJD.Lateralandmedialhypofrontalityinfirst-episodeschizophrenia:functionalactivityinamedication-naivestateandeffectsofshort-termatypicalantipsychotictreatment.AmericanJournalof….2005.

19. SolomonM,OzonoffSJ,CummingsN,CarterCS.Cognitivecontrolinautismspectrumdisorders.InternationalJournalofDevelopmentalNeuroscience.2008;26(2):239-247.doi:10.1016/j.ijdevneu.2007.11.001.

20. SolomonM,OzonoffSJ,UrsuS,etal.Theneuralsubstratesofcognitivecontroldeficitsinautismspectrumdisorders.Neuropsychologia.2009;47(12):2515-2526.doi:10.1016/j.neuropsychologia.2009.04.019.

21. ClaysonPE,LarsonMJ.Psychometricpropertiesofconflictmonitoringandconflictadaptationindices:ResponsetimeandconflictN2event-relatedpotentials.Psychophysiology.2013;50(12):1209-1219.doi:10.1111/psyp.12138.

22. MullaneJC,CorkumPV,KleinRM,McLaughlinE.InterferenceControlinChildrenwithandwithoutADHD:ASystematicReviewofFlankerandSimonTaskPerformance.ChildNeuropsychology.June2009.doi:10.1080/09297040802348028.

23. KernsJG,CohenJD,MacDonaldAW,ChoRY,StengerVA,CarterCS.AnteriorCingulateConflictMonitoringandAdjustmentsinControl.Science.2004;303(5660):1023-1026.doi:10.1126/science.1089910.

24. BarchDM,MooreH,NeeDE,ManoachDS,LuckSJ.CNTRICSImagingBiomarkersSelection:WorkingMemory.SchizophrBull.November2011:sbr160.doi:10.1093/schbul/sbr160.

25. JonidesJ,SchumacherEH,SmithEE,etal.VerbalWorkingMemoryLoadAffectsRegionalBrainActivationasMeasuredbyPET.http://dxdoiorg/101162/jocn199794462.January2008.doi:10.1162/jocn.1997.9.4.462.

26. GillettR.AssessmentofWorkingMemoryPerformanceinSelf-OrderedSelectionTests.

Cortex.2007;43(8):1047-1056.doi:10.1016/S0010-9452(08)70702-0.27. HorwitzB,TagametsMA.Predictinghumanfunctionalmapswithneuralnetmodeling.

Humanbrainmapping.1999.28. NelsonJK,Reuter-LorenzPA,SylvesterC-YC,JonidesJ,SmithEE.Dissociableneural

mechanismsunderlyingresponse-basedandfamiliarity-basedconflictinworkingmemory.PNAS.2003;100(19):11171-11175.doi:10.1073/pnas.1334125100.

29. EgelandJ.MeasuringWorkingMemoryWithDigitSpanandtheLetter-NumberSequencingSubtestsFromtheWAIS-IV:TooLowManipulationLoadandRiskforUnderestimatingModalityEffects.AppliedNeuropsychology:Adult.2015;22(6):445-451.doi:10.1080/23279095.2014.992069.

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.

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

• 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.

• 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.

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.

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.

AppendixSSP-I:Ratingsforrecommendedtasksontaskcriteria

Criteria(Rateeachonascaleof1-5,with1=doesnotdoagoodjobofmeetingthecriterion;

5=doesanexcellentjobmeetingthecriterion

Construct

ValidM

easure

struct

Test-Retest

Reliability

iling/

PracticeEffects

Longitud

Sensitiveto

w/inpe

dardized

rameters

Canitbeused

acrossm

sites?

Canitbeused

withkidsor

special

lation

Arenormative

dataavailable?

Arerelationsto

clinicalfe

atures

copyrighted?

AttachmentandAffiliation

1.Directbrainandbehaviormeasuresofrejectionsensitivity(Cyberball,ChatRoom)

2.SocialMotivation–Approach/Avoidance(e.g.,SocialIncentiveDelayTask;DotProbe/AttentionBias;One-Armed-BanditTaskandotherneuroeconomicstasks)

3.Selfreportofneedforaffiliation/rejectionsensitivity(MultidimensionalScaleofPerceived

SocialSupport;AnhedoniaScale;RejectionSensitivityScale;AffiliationTendencyScale)

SocialCommunication

ReceptionofFacialCommunication

Jointattention,responding(gazecuing);

FacialEmotion(facescanpaths;ER40)

ProductionofFacialCommunication

Jointattention,initiating

Initiateemotionalexpression(EMG/FACS/FACESwithprovocativecontext–IAPS/AffectiveComputing)

Mimicry/Imitateemotionalexpression(FACScoding/EMG

ReceptionofNon-FacialCommunication

SocialResponsivenessScale(SRS)

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

4 3 4 4 3 ? 4 5 5 ? 3 5

PerceptionandUnderstandingofOthers

Animacyperception

Pointlightdisplaysofbiologicalmotion

HeiderandSimmeltypefilms(goal-directed)

5 3 4 3 3 4 3 5 5 3 5 5

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)

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.

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.

• 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.

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

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.

• -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

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.

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.

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

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,

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

• Geneexpressionpatterns140-142• Pupillarylightreflex143

Consideredbutnotrecommended

• Cortisol(toomanyotherfactorscanaffectdata)• Corebodytemperature(tooinvasive,melatoninfairlyequivalent)

References1. ZisnerA,BeauchaineTP.Psychophysiologicalmethodsanddevelopmentalpsychopathology.In:

CicchettiD,CohenDJ,eds.DevelopmentalPsychopathology.Vol2.DevelopmentalNeuroscience.Vol2.Hoboken,NJ:WIley.

2. BeauchaineTP,ThayerJF.Heartratevariabilityasatransdiagnosticbiomarkerofpsychopathology.InternationalJournalofPsychophysiology.2015;98(2):338-350.doi:10.1016/j.ijpsycho.2015.08.004.

3. BeauchaineTP,Gatzke-KoppLM.Instantiatingthemultiplelevelsofanalysisperspectiveinaprogramofstudyonexternalizingbehavior.DevelopmentandPsychopathology.2012;24(03):1003-1018.doi:10.1017/S0954579412000508.

4. BerntsonGG,CacioppoJT,QuigleyKS.Cardiacpsychophysiologyandautonomicspaceinhumans:Empiricalperspectivesandconceptualimplications.PsychologicalBulletin.1993;114(2):296.doi:10.1037/0033-2909.114.2.296.

5. SherwoodA.Useofimpedancecardiographyincardiovascularreactivityresearch.In:BlascovichJ,KatkinES,eds.CardiovascularReactivitytoPsychologicalStreeandDisease.Washington:AmericanPsychologicalAssociation;1993:157-199.doi:10.1037/10125-007.

6. SherwoodA,TurnerJR.Aconceptualandmethodologicaloverviewofcardiovascularreactivityresearch.In:TurnerJR,SherwoodA,LightKC,eds.IndividualDifferencesinCardiovascularResponsetoStress.NewYork,NY.

7. RitzT.Studyingnoninvasiveindicesofvagalcontrol:Theneedforrespiratorycontrolandtheproblemoftargetspecificity.BiologicalPsychology.2009;80(2):158-168.doi:10.1016/j.biopsycho.2008.08.003.

8. CipryanL,LitschmannovaM.Intra-dayandinter-dayreliabilityofheartratevariabilitymeasurement.JournalofSportsSciences.2013;31(2):150-158.doi:10.1080/02640414.2012.721931.

9. RelandS,VilleNS,WongS,CarraultG,CarréF.Reliabilityofheartratevariabilityinhealthyolderwomenatrestandduringorthostatictesting.AgingClinExpRes.2005;17(4):316-321.doi:10.1007/BF03324616.

10. SandercockGRH,BromleyPD,BrodieDA.Thereliabilityofshort-termmeasurementsofheartratevariability.InternationalJournalofCardiology.2005;103(3):238-247.doi:10.1016/j.ijcard.2004.09.013.

11. TakshitaSookanAJM.Heartratevariabilityinphysicallyactiveindividuals:reliabilityandgendercharacteristics.CardiovascularJournalofAfrica.2012;23(2):67.doi:10.5830/CVJA-2011-018.

12. ShaderTM,Gatzke-KoppLM,CrowellSE,etal.Quantifyingrespiratorysinusarrhythmia:Effectsofmisspecifyingbreathingfrequenciesacrossdevelopment.UnderReview.

13. FlemingS,ThompsonM,StevensR,etal.Normalrangesofheartrateandrespiratoryrateinchildrenfrombirthto18yearsofage:Asystematicreviewofobservationalstudies.TheLancet.

2011;377(9770):1011-1018.doi:10.1016/S0140-6736(10)62226-X.14. NUNAND,SandercockGRH,BrodieDA.AQuantitativeSystematicReviewofNormalValuesfor

Short-TermHeartRateVariabilityinHealthyAdults.PacingandClinicalElectrophysiology.2010;33(11):1407-1417.doi:10.1111/j.1540-8159.2010.02841.x.

15. BeauchaineTP.FutureDirectionsinEmotionDysregulationandYouthPsychopathology.JournalofClinicalChild&AdolescentPsychology.May2015.doi:10.1080/15374416.2015.1038827.

16. BeauchaineTP,Gatzke-KoppL,MeadHK.PolyvagalTheoryanddevelopmentalpsychopathology:Emotiondysregulationandconductproblemsfrompreschooltoadolescence.BiologicalPsychology.2007;74(2):174-184.doi:10.1016/j.biopsycho.2005.08.008.

17. YaroslavskyI,RottenbergJ.Atypicalpatternsofrespiratorysinusarrhythmiaindexanendophenotypefordepression.Developmentand….2014.

18. YaroslavskyI,RottenbergJ,BylsmaLM,etal.Parasympatheticnervoussystemactivitypredictsmoodrepairuseanditseffectivenessamongadolescentswithandwithouthistoriesofmajordepression.JournalofAbnormalPsychology.2016;125(3):323.doi:10.1037/abn0000149.

19. NeijtsM,VanLienR,KupperN,BoomsmaD,WillemsenG,GeusEJC.Heritabilityofcardiacvagalcontrolin24-hheartratevariabilityrecordings:Influenceofceilingeffectsatlowheartrates.Psychophysiology.2014;51(10):1023-1036.doi:10.1111/psyp.12246.

20. RieseH,MuñozLM,HartmanCA,etal.IdentifyingGeneticVariantsforHeartRateVariabilityintheAcetylcholinePathway.PLOSONE.2014;9(11):e112476.doi:10.1371/journal.pone.0112476.

21. SuS,LampertR,ZhaoJ,etal.PleiotropyofC-ReactiveProteinGenePolymorphismsWithC-ReactiveProteinLevelsandHeartRateVariabilityinHealthyMaleTwins.TheAmericanJournalofCardiology.2009;104(12):1748-1754.doi:10.1016/j.amjcard.2009.07.063.

22. SuS,LampertR,LeeF,BremnerJD.Commongenescontributetodepressivesymptomsandheartratevariability:theTwinsHeartStudy.…HumanGenetics.2010.

23. RichardJenningsJ,AllenB,GianarosPJ,ThayerJF,ManuckSB.Focusingneurovisceralintegration:Cognition,heartratevariability,andcerebralbloodflow.Psychophysiology.2015;52(2):214-224.doi:10.1111/psyp.12319.

24. JenningsJR,SheuLK,KuanDCH,ManuckSB,GianarosPJ.Restingstateconnectivityofthemedialprefrontalcortexcovarieswithindividualdifferencesinhigh-frequencyheartratevariability.Psychophysiology.2016;53(4):444-454.doi:10.1111/psyp.12586.

25. ThayerJF,HansenAL,Saus-RoseE,JohnsenBH.HeartRateVariability,PrefrontalNeuralFunction,andCognitivePerformance:TheNeurovisceralIntegrationPerspectiveonSelf-regulation,Adaptation,andHealth.annbehavmed.2009;37(2):141-153.doi:10.1007/s12160-009-9101-z.

26. MakovacE,MeetenF,WatsonDR,etal.AlterationsinAmygdala-PrefrontalFunctionalConnectivityAccountforExcessiveWorryandAutonomicDysregulationinGeneralizedAnxietyDisorder.BiologicalPsychiatry.October2015.doi:10.1016/j.biopsych.2015.10.013.

27. SmithR,AllenJJB,ThayerJF,FortC,LaneRD.IncreasedassociationovertimebetweenregionalfrontallobeBOLDchangemagnitudeandcardiacvagalcontrolwithsertralinetreatmentformajordepression.PsychiatryResearch-Neuroimaging.2014;224(3):225-233.doi:10.1016/j.pscychresns.2014.08.015.

28. BeauchaineTP,Gatzke-KoppL,NeuhausE,ChipmanJ,ReidMJ,Webster-StrattonC.Sympathetic-andparasympathetic-linkedcardiacfunctionandpredictionofexternalizingbehavior,emotionregulation,andprosocialbehavioramongpreschoolerstreatedforADHD.JournalofConsultingandClinicalPsychology.2013;81(3):481.doi:10.1037/a0032302.

29. GarakaniA,MartinezJM,AaronsonCJ,VoustianioukA,KaufmannH,GormanJM.Effectofmedicationandpsychotherapyonheartratevariabilityinpanicdisorder.Depressionand

Anxiety.2009;26(3):251-258.doi:10.1002/da.20533.30. PosadzkiP,KuzdzalA,LeeMS,ErnstE.YogaforHeartRateVariability:ASystematicReviewand

Meta-analysisofRandomizedClinicalTrials.AppliedPsychophysiologyBiofeedback.2015;40(3):239-249.doi:10.1007/s10484-015-9291-z.

31. ReineckeA,FilippiniN,BernaC,etal.EffectiveemotionregulationstrategiesimprovefMRIandECGmarkersofpsychopathologyinpanicdisorder:Implicationsforpsychologicaltreatmentaction.TranslationalPsychiatry.2015;5.doi:10.1038/tp.2015.160.

32. WangSM,LeeHK,KweonYS,etal.Effectofemotionregulationtraininginpatientswithpanicdisorder:Evidencedbyheartratevariabilitymeasures.GeneralHospitalPsychiatry.2016;40:68-73.doi:10.1016/j.genhosppsych.2016.01.003.

33. ClamorA,LincolnTM,ThayerJF,KoenigJ.Restingvagalactivityinschizophrenia:Meta-Analysisofheartratevariabilityasapotentialendophenotype.BritishJournalofPsychiatry.2016;208(1):9-16.doi:10.1192/bjp.bp.114.160762.

34. BassettD.Aliteraturereviewofheartratevariabilityindepressiveandbipolardisorders.AustralianandNewZealandJournalofPsychiatry.2015;50(6):511-519.doi:10.1177/0004867415622689.

35. DawsonME,SchellAM,FilionDL.Theelectrodermalsystem.In:CacioppoJT,TassinaryLG,BerntsonGG,eds.HandbookofPsychophysiology.3rded.NewYork;2007:159-181.

36. BoucseinW.ElectrodermalActivity.Boston,MA:SpringerUS;2011.doi:10.1007/978-1-4614-1126-0_1.

37. WilliamsLM,PhillipsML,BrammerMJ,etal.ArousalDissociatesAmygdalaandHippocampalFearResponses:EvidencefromSimultaneousfMRIandSkinConductanceRecording.NeuroImage.2001;14(5):1070-1079.doi:10.1006/nimg.2001.0904.

38. CriderA,KremenWS,XianH,etal.Stability,consistency,andheritabilityofelectrodermalresponselabilityinmiddle-agedmaletwins.Psychophysiology.2004;41(4):501-509.doi:10.1111/j.1469-8986.2004.00189.x.

39. VaidyanathanU,IsenJD,MaloneSM,MillerMB,McGueM,IaconoWG.Heritabilityandmoleculargeneticbasisofelectrodermalactivity:Agenome-wideassociationstudy.Psychophysiology.2014;51(12):1259-1271.doi:10.1111/psyp.12346.

40. BoucseinW,FowlesDC,GrimnersS,etal.Publicationrecommendationsforelectrodermalmeasurements.Psychophysiology.2012;49(8):1017-1034.doi:10.1111/j.1469-8986.2012.01384.x.

41. HerpertzSC,MuellerB,WenningB,QunaibiM,LichterfeldC,Herpertz-DahlmannB.Autonomicresponsesinboyswithexternalizingdisorders.JNeuralTransm.2003;110(10):1181-1195.doi:10.1007/s00702-003-0026-6.

42. HERPERTZSC,VLOETT,MUELLERB,DOMESG,WILLMESK,HERPERTZ-DAHLMANNB.SimilarAutonomicResponsivityinBoysWithConductDisorderandTheirFathers.JournaloftheAmericanAcademyofChild&AdolescentPsychiatry.2007;46(4):535-544.doi:10.1097/chi.0b013e3180306286.

43. IsenJD,IaconoWG,MaloneSM,McGueM.Examiningelectrodermalhyporeactivityasamarkerofexternalizingpsychopathology:Atwinstudy.Psychophysiology.2012;49(8):1039-1048.doi:10.1111/j.1469-8986.2012.01394.x.

44. IsenJD,IaconoWG,MaloneSM.Characterizingelectrodermalresponsehabituation:Alatentclassapproachwithapplicationtopsychopathology.Psychophysiology.2013;50(10):954-962.doi:10.1111/psyp.12080.

45. KnottVJ,BulmerDR.Effectsofrepetitivehighintensitystimulationonelectrodermalresponsivityinmalealcoholicsandnormalcontrols.AddictiveBehaviors.1985;10(2):181-185.doi:10.1016/0306-4603(85)90025-5.

46. RaineA,LenczT,BihrleS,LaCasseL,CollettiP.Reducedprefrontalgraymattervolumeandreducedautonomicactivityinantisocialpersonalitydisorder.ArchivesofGeneralPsychiatry.2000;57(2):119-127.doi:10.1001/archpsyc.57.2.119.

47. RaineA.BiosocialStudiesofAntisocialandViolentBehaviorinChildrenandAdults:AReview.JAbnormChildPsychol.2002;30(4):311-326.doi:10.1023/A:1015754122318.

48. IaconoWG,FickenJW,BeiserM.Electrodermalactivationinfirst-episodepsychoticpatientsandtheirfirst-degreerelatives.PsychiatryResearch.1999;88(1):25-39.doi:10.1016/S0165-1781(99)00071-2.

49. McTeagueLM,LangPJ,LaplanteM-C,CuthbertBN,ShumenJR,BradleyMM.AversiveImageryinPosttraumaticStressDisorder:TraumaRecurrence,Comorbidity,andPhysiologicalReactivity.BiologicalPsychiatry.2010;67(4):346-356.doi:10.1016/j.biopsych.2009.08.023.

50. PoleN.ThePsychophysiologyofPosttraumaticStressDisorder:AMeta-Analysis.PsychologicalBulletin.2007;133(5):725-746.doi:10.1037/0033-2909.133.5.725.

51. GilzenratMS,NieuwenhuisS,JepmaM,CohenJD.Pupildiametertrackschangesincontrolstatepredictedbytheadaptivegaintheoryoflocuscoeruleusfunction.CognAffectBehavNeurosci.2010;10(2):252-269.doi:10.3758/CABN.10.2.252.

52. KossMC.Pupillarydilationasanindexofcentralnervoussystemα2-adrenoceptoractivation.JournalofPharmacologicalMethods.1986;15(1):1-19.doi:10.1016/0160-5402(86)90002-1.

53. HessEH,PoltJM.PupilSizeasRelatedtoInterestValueofVisualStimuli.Science.1960;132(3423):349-350.doi:10.1126/science.132.3423.349.

54. KahnemanD,BeattyJ.PupilDiameterandLoadonMemory.Science.1966;154(3756):1583-1585.doi:10.1126/science.154.3756.1583.

55. WierdaSM,vanRijnH,TaatgenNA,MartensS.Pupildilationdeconvolutionrevealsthedynamicsofattentionathightemporalresolution.PNAS.2012;109(22):8456-8460.doi:10.1073/pnas.1201858109.

56. SiegleGJ,SteinhauerSR,StengerVA,KoneckyR,CarterCS.UseofconcurrentpupildilationassessmenttoinforminterpretationandanalysisoffMRIdata.NeuroImage.2003;20(1):114-124.doi:10.1016/S1053-8119(03)00298-2.

57. LaengB,SiroisS,GredebäckG.Pupillometry:AWindowtothePreconscious?PerspectivesonPsychologicalScience.2012;7(1):18-27.doi:10.1177/1745691611427305.

58. FarzinF,ScaggsF,HerveyC,Berry-KravisE,HesslD.ReliabilityofEyeTrackingandPupillometryMeasuresinIndividualswithFragileXSyndrome.JAutismDevDisord.2011;41(11):1515-1522.doi:10.1007/s10803-011-1176-2.

59. SiegleGJ,SteinhauerSR,FriedmanES,ThompsonWS,ThaseME.RemissionPrognosisforCognitiveTherapyforRecurrentDepressionUsingthePupil:UtilityandNeuralCorrelates.BiologicalPsychiatry.2011;69(8):726-733.doi:10.1016/j.biopsych.2010.12.041.

60. AndersonCJ,ColomboJ,ShaddyDJ.VisualScanningandPupillaryResponsesinYoungChildrenwithAutismSpectrumDisorder.JournalofClinicalandExperimentalNeuropsychology.February2007.doi:10.1080/13803390500376790.

61. MartineauJ,HernandezN,HiebelL,RochéL,MetzgerA,Bonnet-BrilhaultF.Canpupilsizeandpupilresponsesduringvisualscanningcontributetothediagnosisofautismspectrumdisorderinchildren?JournalofPsychiatricResearch.2011;45(8):1077-1082.doi:10.1016/j.jpsychires.2011.01.008.

62. PriceRB,SiegleGJ,SilkJS,etal.SUSTAINEDNEURALALTERATIONSINANXIOUSYOUTHPERFORMINGANATTENTIONALBIASTASK:APUPILOMETRYSTUDY.DepressionandAnxiety.2013;30(1):22-30.doi:10.1002/da.21966.

63. SilkJSPh.D.,DahlREM.D.,RyanNDM.D.,etal.PupillaryReactivitytoEmotionalInformationinChildandAdolescentDepression:LinkstoClinicalandEcologicalMeasures.AmericanJournalof

Psychiatry.2007;164(12):1873-1880.doi:10.1176/appi.ajp.2007.06111816.64. SherwoodA,AllenMT,FahrenbergJ,KelseyRM,LovalloWR,vanDoornenLJP.Methodological

GuidelinesforImpedanceCardiography.Psychophysiology.1990;27(1):1-23.doi:10.1111/j.1469-8986.1990.tb02171.x.

65. SherwoodA,AllenMT,ObristPA,LangerAW.EvaluationofBeta-AdrenergicInfluencesonCardiovascularandMetabolicAdjustmentstoPhysicalandPsychologicalStress.Psychophysiology.1986;23(1):89-104.doi:10.1111/j.1469-8986.1986.tb00602.x.

66. MillsPJ,DimsdaleJE.Sympatheticnervoussystemresponsestopsychosocialstressors.In:TurnerJR,SherwoodA,LightKC,eds.IndividualDifferencesinCardiovascularResponsetoStress.NewYork:Springer;2013:3-32.

67. RichterM,GendollaGHE.Theheartcontractstoreward:Monetaryincentivesandpreejectionperiod.Psychophysiology.2009;46(3):451-457.doi:10.1111/j.1469-8986.2009.00795.x.

68. BrennerSL,BeauchaineTP,SylversPD.Acomparisonofpsychophysiologicalandself-reportmeasuresofBASandBISactivation.Psychophysiology.2005;42(1):108-115.doi:10.1111/j.1469-8986.2005.00261.x.

69. KelseyRM,OrnduffSR,AlpertBS.Reliabilityofcardiovascularreactivitytostress:Internalconsistency.Psychophysiology.2007;44(2):216-225.doi:10.1111/j.1469-8986.2007.00499.x.

70. SherwoodA,GIRDLERSS,BRAGDONEE,etal.Ten-yearstabilityofcardiovascularresponsestolaboratorystressors.Psychophysiology.1997;34(2):185-191.doi:10.1111/j.1469-8986.1997.tb02130.x.

71. UchinoBN,UnoD,Holt-LunstadJ,FlindersJB.Age-RelatedDifferencesinCardiovascularReactivityDuringAcutePsychologicalStressinMenandWomen.JGerontolBPsycholSciSocSci.1999;54B(6):P339-P346.doi:10.1093/geronb/54B.6.P339.

72. BeauchaineTP,KatkinES,StrassbergZ,SnarrJ.Disinhibitorypsychopathologyinmaleadolescents:Discriminatingconductdisorderfromattention-deficit/hyperactivitydisorderthroughconcurrentassessmentofmultipleautonomicstates.JournalofAbnormalPsychology.2001;110(4):610.doi:10.1037/0021-843X.110.4.610.

73. MarshP,BeauchaineTP,WilliamsB.Dissociationofsadfacialexpressionsandautonomicnervoussystemrespondinginboyswithdisruptivebehaviordisorders.Psychophysiology.2008;45(1):100-110.doi:10.1111/j.1469-8986.2007.00603.x.

74. BeauchaineTP,HongJ,MarshP.SexDifferencesinAutonomicCorrelatesofConductProblemsandAggression.JournaloftheAmericanAcademyofChild&AdolescentPsychiatry.2008;47(7):788-796.doi:10.1097/CHI.Ob013e318172ef4b.

75. QuigleyKS,StifterCA.Acomparativevalidationofsympatheticreactivityinchildrenandadults.Psychophysiology.2006;43(4):357-365.doi:10.1111/j.1469-8986.2006.00405.x.

76. deGeusEJC,KupperN,BoomsmaDI,SniederH.BivariateGeneticModelingofCardiovascularStressReactivity:DoesStressUncoverGeneticVariance?PsychosomaticMedicine.2007;69(4):356.doi:10.1097/PSY.0b013e318049cc2d.

77. KupperN,WillemsenG,BoomsmaDI,deGeusEJC.HeritabilityofIndicesforCardiacContractilityinAmbulatoryRecordings.JournalofCardiovascularElectrophysiology.2006;17(8):877-883.doi:10.1111/j.1540-8167.2006.00535.x.

78. SniederH,HarshfieldGA,BarbeauP,PollockDM,PollockJS,TreiberFA.Dissectingthegeneticarchitectureofthecardiovascularandrenalstressresponse.BiologicalPsychology.2002;61(1-2):73-95.doi:10.1016/S0301-0511(02)00053-4.

79. BuuseM.ROLEOFTHEMESOLIMBICDOPAMINESYSTEMINCARDIOVASCULARHOMEOSTASIS.STIMULATIONOFTHEVENTRALTEGMENTALAREAMODULATESTHEEFFECTOFVASOPRESSINONBLOODPRESSUREINCONSCIOUSRATS.ClinicalandExperimentalPharmacologyandPhysiology.1998;25(9):661-668.doi:10.1111/j.1440-1681.1998.tb02273.x.

80. SalomonK,BylsmaLM,WhiteKE,PanaiteV,RottenbergJ.Isbluntedcardiovascularreactivityindepressionmood-statedependent?Acomparisonofmajordepressivedisorderremitteddepressionandhealthycontrols.InternationalJournalofPsychophysiology.2013;90(1):50-57.doi:10.1016/j.ijpsycho.2013.05.018.

81. BrennerSL,BeauchaineTP.Pre-ejectionperiodreactivityandpsychiatriccomorbidityprospectivelypredictsubstanceuseinitiationamongmiddle-schoolers:Apilotstudy.Psychophysiology.2011;48(11):1588-1596.doi:10.1111/j.1469-8986.2011.01230.x.

82. TamakiM,BangJW,WatanabeT,SasakiY.NightWatchinOneBrainHemisphereduringSleepAssociatedwiththeFirst-NightEffectinHumans.CurrentBiology.2016;26(9):1190-1194.doi:10.1016/j.cub.2016.02.063.

83. COTEKA,MILNERCE,SMITHBA,etal.CNSarousalandneurobehavioralperformanceinashort-termsleeprestrictionparadigm.JournalofSleepResearch.2009;18(3):291-303.doi:10.1111/j.1365-2869.2008.00733.x.

84. BasnerM,MolliconeD,DingesDF.Validityandsensitivityofabriefpsychomotorvigilancetest(PVT-B)tototalandpartialsleepdeprivation.ActaAstronautica.2011;69(11-12):949-959.doi:10.1016/j.actaastro.2011.07.015.

85. ChristieMA,BolortuyaY,ChenLC,McKennaJT,McCarleyRW,StreckerRE.Microdialysiselevationofadenosineinthebasalforebrainproducesvigilanceimpairmentsintheratpsychomotorvigilancetask.Sleep.2008;31(10):1393-1398.

86. DrummondS,Bischoff-GretheA.Theneuralbasisofthepsychomotorvigilancetask.SLEEP-NEWYORK….2005.

87. RéteyJV,AdamM,GottseligJM,etal.Adenosinergicmechanismscontributetoindividualdifferencesinsleepdeprivation-inducedchangesinneurobehavioralfunctionandbrainrhythmicactivity.JournalofNeuroscience.2006;26(41):10472-10479.doi:10.1523/JNEUROSCI.1538-06.2006.

88. IberC,Ancoli-IsraelC,ChessonA,QuanSF.TheAASMManualfortheScoringofSleepandAssociatedEvents:Rules,TerminologyandTechnicalSpecification.1sted.Weschester,IL:AmericanAcademyofSleepMedicine;2007.

89. KrystalAD,EdingerJD.Measuringsleepquality.SleepMedicine.2008;9:S10-S17.doi:10.1016/S1389-9457(08)70011-X.

90. SilberMH,Ancoli-IsraelS,BonnetMH.Thevisualscoringofsleepinadults.JClinSleep….2007.91. WarbySC,WendtSL,WelinderP,etal.Sleep-spindledetection:crowdsourcingandevaluating

performanceofexperts,non-expertsandautomatedmethods.NatureMethods.2014;11(4):385-392.doi:10.1038/nmeth.2855.

92. ClawsonBC,DurkinJ,AtonSJ.FormandFunctionofSleepSpindlesacrosstheLifespan.NeuralPlasticity.2016;2016(17):1-16.doi:10.1155/2016/6936381.

93. AstoriS,WimmerRD,ProsserHM,etal.TheCaV3.3calciumchannelisthemajorsleepspindlepacemakerinthalamus.PNAS.2011;108(33):13823-13828.doi:10.1073/pnas.1105115108.

94. ManoachDS,PanJQ,PurcellSM,StickgoldR.ReducedSleepSpindlesinSchizophrenia:ATreatableEndophenotypeThatLinksRiskGenestoImpairedCognition?BiologicalPsychiatry.October2015.doi:10.1016/j.biopsych.2015.10.003.

95. WellsMF,WimmerRD,SchmittLI,FengG,HalassaMM.ThalamicreticularimpairmentunderliesattentiondeficitinPtchd1Y/−mice.Nature.2016;532(7597):58-63.doi:10.1038/nature17427.

96. FogelSM,SmithCT.Thefunctionofthesleepspindle:Aphysiologicalindexofintelligenceandamechanismforsleep-dependentmemoryconsolidation.Neuroscience&BiobehavioralReviews.2011;35(5):1154-1165.doi:10.1016/j.neubiorev.2010.12.003.

97. ManoachDS,CainMS,VangelMG,KhuranaA,GoffDC,StickgoldR.Afailureofsleep-

dependentprocedurallearninginchronic,medicatedschizophrenia.BiologicalPsychiatry.2004;56(12):951-956.doi:10.1016/j.biopsych.2004.09.012.

98. ManoachDS,DemanueleC,WamsleyEJ,etal.Sleepspindledeficitsinantipsychotic-naïveearlycourseschizophreniaandinnon-psychoticfirst-degreerelatives.FrontHumNeurosci.2014;8:344.doi:10.3389/fnhum.2014.00762.

99. LustenbergerC,BoyleMR,AlagapanS,MellinJM,VaughnBV,FröhlichF.Feedback-ControlledTranscranialAlternatingCurrentStimulationRevealsaFunctionalRoleofSleepSpindlesinMotorMemoryConsolidation.CurrentBiology.2016;26(16):2127-2136.doi:10.1016/j.cub.2016.06.044.

100. MednickSC,McDevittEA,WalshJK,etal.TheCriticalRoleofSleepSpindlesinHippocampal-DependentMemory:APharmacologyStudy.JNeurosci.2013;33(10):4494-4504.doi:10.1523/JNEUROSCI.3127-12.2013.

101. KalesA,RechtschaffenA.AManualofStandardizedTerminology,TechniquesandScoringSystemforSleepStagesofHumanSubjects.

102. BrunnerDP,DijkD-J,ToblerI,BorbélyAA.EffectofpartialsleepdeprivationonsleepstagesandEEGpowerspectra:evidencefornon-REMandREMsleephomeostasis.ElectroencephalographyandClinicalNeurophysiology.1990;75(6):492-499.doi:10.1016/0013-4694(90)90136-8.

103. BrunnerDP,DijkD-J,BorbélyAA.RepeatedpartialsleepdeprivationprogressivelychangestheEEGduringsleepandwakefulness.Sleep:JournalofSleepResearch&SleepMedicine.February1993.

104. DijkD-J,HayesB,CzeislerCA.Dynamicsofelectroencephalographicsleepspindlesandslowwaveactivityinmen:effectofsleepdeprivation.BrainResearch.1993;626(1):190-199.doi:10.1016/0006-8993(93)90579-C.

105. DJD,CC,IT,AAB.Sleepextensioninhumans:sleepstages,EEGpowerspectraandbodytemperature.Sleep:JournalofSleepResearch&SleepMedicine.1991;14(4):294-306.

106. DijkD-J,BrunnerDP,BeersmaD,AAB.Electroencephalogrampowerdensityandslowwavesleepasafunctionofpriorwakingandcircadianphase.Sleep.1990.

107. DijkDJ,BrunnerDP,BorbélyAA.TimecourseofEEGpowerdensityduringlongsleepinhumans.AmericanJournalofPhysiology-Regulatory,IntegrativeandComparativePhysiology.1990;258(3):R650-R661.

108. DijkD-J,BrunnerDP,BorbélyAA.EEGpowerdensityduringrecoverysleepinthemorning.ElectroencephalographyandClinicalNeurophysiology.1991;78(3):203-214.doi:10.1016/0013-4694(91)90034-2.

109. EndoT,SchwierinB,BorbélyAA,ToblerI.Selectiveandtotalsleepdeprivation:effectonthesleepEEGintherat.PsychiatryResearch.1997;66(2-3):97-110.doi:10.1016/S0165-1781(96)03029-6.

110. FrankenP,DijkDJ,ToblerI,BorbélyAA.Sleepdeprivationinrats:effectsonEEGpowerspectra,vigilancestates,andcorticaltemperature.AmericanJournalofPhysiology-Regulatory,IntegrativeandComparativePhysiology.1991;261(1):R198-R208.

111. AndrewDKrystalJDE.SleepEEGPredictorsandCorrelatesoftheResponsetoCognitiveBehavioralTherapyforInsomnia.Sleep.2010;33(5):669.

112. ToblerI,BorbélyAA.SleepEEGintheratasafunctionofpriorwaking.ElectroencephalographyandClinicalNeurophysiology.1986;64(1):74-76.doi:10.1016/0013-4694(86)90044-1.

113. WerthE,DijkDJ,AchermannP,BorbélyAA.DynamicsofthesleepEEGafteranearlyeveningnap:experimentaldataandsimulations.AmericanJournalofPhysiology-Regulatory,IntegrativeandComparativePhysiology.1996;271(3):R501-R510.

114. AchermannP,DijkD-J,BrunnerDP,BorbélyAA.Amodelofhumansleephomeostasisbasedon

EEGslow-waveactivity:Quantitativecomparisonofdataandsimulations.BrainResearchBulletin.1993;31(1-2):97-113.doi:10.1016/0361-9230(93)90016-5.

115. BorbélyAA,BaumannF,BrandeisD,StrauchI,LehmannD.Sleepdeprivation:EffectonsleepstagesandEEGpowerdensityinman.ElectroencephalographyandClinicalNeurophysiology.1981;51(5):483-493.doi:10.1016/0013-4694(81)90225-X.

116. AmericanSOPCOT.Practiceparametersforclinicaluseofthemultiplesleeplatencytestandthemaintenanceofwakefulnesstest.Sleep.2005.

117. DA,MB,TH,MM,RR,RBS.TheclinicaluseoftheMSLTandMWT.Sleep:JournalofSleepResearch&SleepMedicine.2005;28(1):123-144.

118. BastienC.ValidationoftheInsomniaSeverityIndexasanoutcomemeasureforinsomniaresearch.SleepMedicine.2001;2(4):297-307.doi:10.1016/S1389-9457(00)00065-4.

119. KarniA,MeyerG,Rey-HipolitoC,etal.Theacquisitionofskilledmotorperformance:Fastandslowexperience-drivenchangesinprimarymotor cortex.PNAS.1998;95(3):861-868.

120. WalkerMP,BrakefieldT,MorganA,HobsonJA,StickgoldR.PracticewithSleepMakesPerfect.Neuron.2002;35(1):205-211.doi:10.1016/S0896-6273(02)00746-8.

121. AlbouyG,FogelS,PottiezH,etal.DaytimeSleepEnhancesConsolidationoftheSpatialbutNotMotoricRepresentationofMotorSequenceMemory.PLOSONE.2013;8(1):e52805.doi:10.1371/journal.pone.0052805.

122. BarakatM,DoyonJ,DebasK,etal.Fastandslowspindleinvolvementintheconsolidationofanewmotorsequence.BehaviouralBrainResearch.2011;217(1):117-121.doi:10.1016/j.bbr.2010.10.019.

123. NishidaM,WalkerMP.DaytimeNaps,MotorMemoryConsolidationandRegionallySpecificSleepSpindles.PLOSONE.2007;2(4):e341.doi:10.1371/journal.pone.0000341.

124. TamakiM,HuangTR,YotsumotoY,etal.Enhancedspontaneousoscillationsinthesupplementarymotorareaareassociatedwithsleep-dependentofflinelearningoffinger-tappingmotor-sequencetask.JournalofNeuroscience.2013;33(34):13894-13902.doi:10.1523/JNEUROSCI.1198-13.2013.

125. DreslerM,KlugeM,PawlowskiM,SchüsslerP,SteigerA,GenzelL.Adoubledissociationofmemoryimpairmentsinmajordepression.JournalofPsychiatricResearch.2011;45(12):1593-1599.doi:10.1016/j.jpsychires.2011.07.015.

126. WamsleyEJ,TuckerMA,ShinnAK,etal.ReducedSleepSpindlesandSpindleCoherenceinSchizophrenia:MechanismsofImpairedMemoryConsolidation?BiologicalPsychiatry.2012;71(2):154-161.doi:10.1016/j.biopsych.2011.08.008.

127. GenzelL,DreslerM,CornuM,etal.Medialprefrontal-hippocampalconnectivityandmotormemoryconsolidationindepressionandschizophrenia.BiologicalPsychiatry.2015;77(2):177-186.doi:10.1016/j.biopsych.2014.06.004.

128. BackhausJ,BornJ,HoeckesfeldR,FokuhlS,HohagenF,JunghannsK.Midlifedeclineindeclarativememoryconsolidationiscorrelatedwithadeclineinslowwavesleep.LearningandMemory.2007;14(5):336-341.doi:10.1101/lm.470507.

129. BlatterK,CajochenC.Circadianrhythmsincognitiveperformance:Methodologicalconstraints,protocols,theoreticalunderpinnings.Physiology&Behavior.2007;90(2-3):196-208.doi:10.1016/j.physbeh.2006.09.009.

130. GoelN,BasnerM,RaoH,DingesDF.CircadianRhythms,SleepDeprivation,andHumanPerformance.In:Chronobiology:BiologicalTiminginHealthandDisease.Vol119.ProgressinMolecularBiologyandTranslationalScience.Elsevier;2013:155-190.doi:10.1016/B978-0-12-396971-2.00007-5.

131. HermanJH.ChronobiologicMonitoringTechniques.In:PrinciplesandPracticeofSleepMedicine.ElsevierHealthSciences;2010.

132. BurgessHJ,WyattJK,ParkM,FoggLF.Homecircadianphaseassessmentswithmeasuresofcomplianceyieldaccuratedimlightmelatoninonsets.Sleep.2015;38(6):889-897.doi:10.5665/sleep.4734.

133. BenloucifS,BurgessHJ,KlermanEB,etal.Measuringmelatonininhumans.JournalofClinicalSleepMedicine.2008;4(1):66-69.

134. BriscoeS,HardyE,PengoMF,etal.Comparisonof7versus14dayswristactigraphymonitoringinasleepdisordersclinicpopulation.ChronobiologyInternational.2014;31(3):356-362.doi:10.3109/07420528.2013.858163.

135. TahmasianM,KhazaieH,GolshaniS,AvisKT.Clinicalapplicationofactigraphyinpsychoticdisorders:Asystematicreview.CurrentPsychiatryReports.2013;15(6):359.doi:10.1007/s11920-013-0359-2.

136. ManoachDS,ThakkarKN,StroynowskiE,etal.Reducedovernightconsolidationofprocedurallearninginchronicmedicatedschizophreniaisrelatedtospecificsleepstages.JournalofPsychiatricResearch.2010;44(2):112-120.doi:10.1016/j.jpsychires.2009.06.011.

137. HorneJA,OstbergO.AselfassessmentquestionnairetodetermineMorningnessEveningnessinhumancircadianrhythms.InternationalJournalofChronobiology.1976;4(2):97-110.

138. LevandovskiR,SassoE,HidalgoMP.Chronotype:Areviewoftheadvances,limitsandapplicabilityofthemaininstrumentsusedintheliteraturetoassesshumanphenotype.TrendsinPsychiatryandPsychotherapy.2013;35(1):3-11.doi:10.1590/S2237-60892013000100002.

139. RoennebergT,Wirz-JusticeA,MerrowM.Lifebetweenclocks:Dailytemporalpatternsofhumanchronotypes.JournalofBiologicalRhythms.2003;18(1):80-90.doi:10.1177/0748730402239679.

140. ChenCY,LoganRW,MaT,etal.Effectsofagingoncircadianpatternsofgeneexpressioninthehumanprefrontalcortex.ProceedingsoftheNationalAcademyofSciencesoftheUnitedStatesofAmerica.2016;113(1):206-211.doi:10.1073/pnas.1508249112.

141. LechK,AckermannK,RevellVL,LaoOSCAR,SkeneDJ,KayserM.DissectingDailyandCircadianExpressionRhythmsofClock-ControlledGenesinHumanBlood.JournalofBiologicalRhythms.2016;31(1):68-81.doi:10.1177/0748730415611761.

142. ZhangR,LahensNF,BallanceHI,HughesME,HogeneschJB.Acircadiangeneexpressionatlasinmammals:Implicationsforbiologyandmedicine.ProceedingsoftheNationalAcademyofSciencesoftheUnitedStatesofAmerica.2014;111(45):16219-16224.doi:10.1073/pnas.1408886111.

143. MünchM,LéonL,CrippaSV,KawasakiA.Circadianandwake-dependenteffectsonthepupillightreflexinresponsetonarrow-bandwidthlightpulses.InvestigativeOphthalmologyandVisualScience.2012;53(8):4546-4555.doi:10.1167/iovs.12-9494.

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.

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

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.

7.Canthetaskbeusedasastand-alonebehavioraltask?

9.Areadequatenormativedataavailableacrossage,gender,education,ethnicity,SES?Yes.

10.Isthetaskcurrentlyinwideusageorhasitsusebeenlimitedtoafewresearchgroups?Moderateuse.

11.Isthetasksensitivetowithin-personchange?Yes.

12.Canthetaskbeusedwithmethodstointerrogatebraincircuitry(e.g.,fMRI,EEG,etc.)?Yes.

14.Aretherelationshipsbetweentaskperformanceandneuralsignal(s)known?No.

15.Aretherelationshipsbetweentaskperformanceandclinicalfeature(s)known?RelatedtoADHD,sleepdeprivation.

16.Isthetaskfreelydistributed(i.e.,notcopyrighted)?Yes.

17.DoesthetaskassessmultipleRDoCconstructsorisitspecifictojustone?Ifitassessesmultipleconstructs,doesitallowforunambiguousconclusionsaboutthetargetedconstruct?Relatedtoattention/arousal.

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.

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.

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?

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?

10.Isthetaskcurrentlyinwideusageorhasitsusebeenlimitedtoafewresearchgroups?Yes.

11.Isthetasksensitivetowithin-personchange?Yes,changesinresponsetointerventions.

13.Canthetask(oritsanalog)beusedinanimals?Isananimalversionavailable?Yes.

14.Aretherelationshipsbetweentaskperformanceandneuralsignal(s)known?Someinformationavailable.

15.Aretherelationshipsbetweentaskperformanceandclinicalfeature(s)known?Yes;associatedwithmood,anxiety,stress,drugeffects,etc.

17.DoesthetaskassessmultipleRDoCconstructsorisitspecifictojustone?Ifitassessesmultipleconstructs,doesitallowforunambiguousconclusionsaboutthetargetedconstruct?Yes,fairlyspecificforarousal.

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.

7.Canthetaskbeusedasastand-alonebehavioraltask?N/A.

8.Areadequatenormativedataavailableacrossage,gender,education,ethnicity,SES?Pending.

9.Isthetaskcurrentlyinwideusageorhasitsusebeenlimitedtoafewresearchgroups?Usageincreasing.

10.Isthetasksensitivetowithin-personchange?Yes,butmoretrait-like.

14.Aretherelationshipsbetweentaskperformanceandclinicalfeature(s)known?Yes.

16.DoesthetaskassessmultipleRDoCconstructsorisitspecifictojustone?Ifitassessesmultipleconstructs,doesitallowforunambiguousconclusionsaboutthetargetedconstruct?Fairlyspecifictosleep,althoughassociatedwithcognitionaswellassleep.

17.Ifthereisnoexistingtaskavailableforaconstruct,isthereataskthatcouldbemodifiedtofittheconstruct?N/A

APPENDIXARS-If:Summaryofdiscussionofhowwelleachtaskmettheproposedcriteriafortaskevaluation.

Task:MultipleSleepLatencyTest(MSLT)

1.HowstrongistheevidencethatthetaskprovidesavalidmeasureoftheRDoCconstruct?Strongmeasureofsleepiness;consideredagoldstandard.

2.Howgoodistheevidenceaboutthepsychometricscharacteristicsofthetask(e.g.,internalreliability,testretest,floorandceilingeffects,practiceeffects,availabilityofalternateforms,longitudinalstability)?Limitedonlyby“noise”relatedtovariability.

4.Towhatextentisthetask(ordifferentversionsofthetask)suitableforuseacrosslab-basedstudies,clinicaltrials(asameasureoftargetengagementorclinicaloutcome),and/orhigh-throughputscreeningsettings?Limitedbyneedtobeperformedinasleeplaboratory.

5.Isthetaskfreefromfloor/ceilingeffectssothatitcanbeusedacrossindividualswiththefullrangeofperformance/impairmentonthetasks?Yes,ceilingeffect.

7.Canthetaskbeusedasastand-alonebehavioraltask?Yes.

8.Isthetasksuitableforuseinhumansubjectsinavarietyoflabenvironments?Isthetaskfeasibleforadministrationacrosssites?Whatworkisneededtomakethetaskreadyforuseinclinicaltrials?Isusedinmanyofthesesettings.

10.Isthetaskcurrentlyinwideusageorhasitsusebeenlimitedtoafewresearchgroups?Widelyused.

14.Aretherelationshipsbetweentaskperformanceandneuralsignal(s)known?No.

17.DoesthetaskassessmultipleRDoCconstructsorisitspecifictojustone?Ifitassessesmultipleconstructs,doesitallowforunambiguousconclusionsaboutthetargetedconstruct?Specificforsleepiness.

APPENDIXARS-Ig:Summaryofdiscussionofhowwelleachtaskmettheproposedcriteriafortaskevaluation.

Task:Polysomnographically-definedsleeparchitecture(sleeplatency,wakefulnessaftersleeponset,totalsleeptime)

1. HowstrongistheevidencethatthetaskprovidesavalidmeasureoftheRDoCconstruct?Goldstandard.

2.Howgoodistheevidenceaboutthepsychometricscharacteristicsofthetask(e.g.,internalreliability,testretest,floorandceilingeffects,practiceeffects,availabilityofalternateforms,longitudinalstability)?Thereisaflooreffectonsomeparameters(eg,sleeplatencyandWASO),night-to-nightvariabilityandaccommodationeffectssleepinginthesleeplab.

5.Isthetaskfreefromfloor/ceilingeffectssothatitcanbeusedacrossindividualswiththefullrangeofperformance/impairmentonthetasks?Canbeusedacrosswiderangeofindividualsbuttherearesomefloor/ceilingeffectsasnotedabove(2).

7.Canthetaskbeusedasastand-alonebehavioraltask?N/A.

8.Isthetasksuitableforuseinhumansubjectsinavarietyoflabenvironments?Isthetaskfeasibleforadministrationacrosssites?Whatworkisneededtomakethetaskreadyforuseinclinicaltrials?Suitableforuseinavarietyofenvironmentsandhasbeenusedextensivelyinmulti-siteclinicaltrials.

10.Isthetaskcurrentlyinwideusageorhasitsusebeenlimitedtoafewresearchgroups?Widelyutilized.

11.Isthetasksensitivetowithin-personchange?Yes,butlimitedsomewhatbynight-to-nightvariability.

14.Aretherelationshipsbetweentaskperformanceandneuralsignal(s)known?SleepEEGisaneuralsignal.

17.DoesthetaskassessmultipleRDoCconstructsorisitspecifictojustone?Ifitassessesmultipleconstructs,doesitallowforunambiguousconclusionsaboutthetargetedconstruct?Specificforthisconstruct.

APPENDIXARS-Ih:Summaryofdiscussionofhowwelleachtaskmettheproposedcriteriafortaskevaluation.

Task:Slowwavemeasures(declineacrossthenightashomeostaticmeasure,NREMaverageslowwavepower)

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.

5.Isthetaskfreefromfloor/ceilingeffectssothatitcanbeusedacrossindividualswiththefullrangeofperformance/impairmentonthetasks?TherecanbeflooreffectsinindividualswithoutmuchSWA;canbeconfoundedinelderlywithgeneralizedEEGslowing.

7.Canthetaskbeusedasastand-alonebehavioraltask?No;needstobecorrelatedwithothermeasures.

8.Isthetasksuitableforuseinhumansubjectsinavarietyoflabenvironments?Isthetaskfeasibleforadministrationacrosssites?Whatworkisneededtomakethetaskreadyforuseinclinicaltrials?Easytocollectdata,notalllabsanalyzeslowwaves.

10.Isthetaskcurrentlyinwideusageorhasitsusebeenlimitedtoafewresearchgroups?Datacollectedwidelybutnotanalyzedinmanylabs.

17.DoesthetaskassessmultipleRDoCconstructsorisitspecifictojustone?Ifitassessesmultipleconstructs,doesitallowforunambiguousconclusionsaboutthetargetedconstruct?Specifictosleep.

APPENDIXARS-Ii:Summaryofdiscussionofhowwelleachtaskmettheproposedcriteriafortaskevaluation.

Task:InsomniaSeverityIndex(ISI)

1.HowstrongistheevidencethatthetaskprovidesavalidmeasureoftheRDoCconstruct?Validmeasureofinsomniaanddaytimeconsequences.

2.Howgoodistheevidenceaboutthepsychometricscharacteristicsofthetask(e.g.,internalreliability,testretest,floorandceilingeffects,practiceeffects,availabilityofalternateforms,longitudinalstability)?Excellent.

4.Towhatextentisthetask(ordifferentversionsofthetask)suitableforuseacrosslab-basedstudies,clinicaltrials(asameasureoftargetengagementorclinicaloutcome),and/orhigh-throughputscreeningsettings?Easilyused;shortself-administeredscale.

6.Canthetaskbeused(oradaptedforuse)withchildrenandotherspecialpopulations?Canitbeusedacrossagegroups?Canitbeusedacrossdifferentculturalsettings?Notvalidatedinchildren,hasbeentranslatedintoseverallanguages.

7.Canthetaskbeusedasastand-alonebehavioraltask?Notabehavioraltask.

8.Isthetasksuitableforuseinhumansubjectsinavarietyoflabenvironments?Isthetaskfeasibleforadministrationacrosssites?Whatworkisneededtomakethetaskreadyforuseinclinicaltrials?Usedwidelyinclinicaltrials.

10.Isthetaskcurrentlyinwideusageorhasitsusebeenlimitedtoafewresearchgroups?Widelyused.

12.Canthetaskbeusedwithmethodstointerrogatebraincircuitry(e.g.,fMRI,EEG,etc.)?N/A.

13.Canthetask(oritsanalog)beusedinanimals?Isananimalversionavailable?N/A.

17.DoesthetaskassessmultipleRDoCconstructsorisitspecifictojustone?Ifitassessesmultipleconstructs,doesitallowforunambiguousconclusionsaboutthetargetedconstruct?Measuresinsomnia.

APPENDIXARS-Ij:Summaryofdiscussionofhowwelleachtaskmettheproposedcriteriafortaskevaluation.

Task:FingertappingMotorSequenceTask(MST)

1.HowstrongistheevidencethatthetaskprovidesavalidmeasureoftheRDoCconstruct?Validmeasureofsleepdependentmemoryconsolidation.

2.Howgoodistheevidenceaboutthepsychometricscharacteristicsofthetask(e.g.,internalreliability,testretest,floorandceilingeffects,practiceeffects,availabilityofalternateforms,longitudinalstability)?Gooddataontheseparameters.

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.

8.Isthetasksuitableforuseinhumansubjectsinavarietyoflabenvironments?Isthetaskfeasibleforadministrationacrosssites?Whatworkisneededtomakethetaskreadyforuseinclinicaltrials?Feasibletouseacrosssites.Usedinclinicaltrials.

9.Areadequatenormativedataavailableacrossage,gender,education,ethnicity,SES?No.

10.Isthetaskcurrentlyinwideusageorhasitsusebeenlimitedtoafewresearchgroups?Mostwidelyusedprobeforsleep-dependentlearning,butnotalotoflabsworkingonthis.

13.Canthetask(oritsanalog)beusedinanimals?Isananimalversionavailable?N/A.

14.Aretherelationshipsbetweentaskperformanceandneuralsignal(s)known?Neuroimagingstudiesexist,butnotmany.

17.DoesthetaskassessmultipleRDoCconstructsorisitspecifictojustone?Ifitassessesmultipleconstructs,doesitallowforunambiguousconclusionsaboutthetargetedconstruct?Measuressleep-dependentlearning/restorativeaspectsofsleepfairlyspecifically.

APPENDIXARS-Ik:Summaryofdiscussionofhowwelleachtaskmettheproposedcriteriafortaskevaluation.

Task:Dimlightmelatoninonset(DLMO)

Construct:CIRCADIANRHYTHMS

1.HowstrongistheevidencethatthetaskprovidesavalidmeasureoftheRDoCconstruct?Verystrong.

2.Howgoodistheevidenceaboutthepsychometricscharacteristicsofthetask(e.g.,internalreliability,testretest,floorandceilingeffects,practiceeffects,availabilityofalternateforms,longitudinalstability)?Probablythebestmarkerforcircadianphase;caveatisthatsomesubjectshavelowlevelsofmelatonin.

4.Towhatextentisthetask(ordifferentversionsofthetask)suitableforuseacrosslab-basedstudies,clinicaltrials(asameasureoftargetengagementorclinicaloutcome),and/orhigh-throughputscreeningsettings?Notidealforhigh-throughputstudies,otherwiseusefulinclinicalresearch/trials.

5.Isthetaskfreefromfloor/ceilingeffectssothatitcanbeusedacrossindividualswiththefullrangeofperformance/impairmentonthetasks?Fewsubjectsmayhavelowlevels(flooreffect).

8.Isthetasksuitableforuseinhumansubjectsinavarietyoflabenvironments?Isthetaskfeasibleforadministrationacrosssites?Whatworkisneededtomakethetaskreadyforuseinclinicaltrials?Yes.

9.Areadequatenormativedataavailableacrossage,gender,education,ethnicity,SES?Somedatainpublishedstudies.

10.Isthetaskcurrentlyinwideusageorhasitsusebeenlimitedtoafewresearchgroups?Usedinanumberoflabs;samplesneedtoberunbyqualifiedlabs.

12.Canthetaskbeusedwithmethodstointerrogatebraincircuitry(e.g.,fMRI,EEG,etc.)?N/A.

15.Aretherelationshipsbetweentaskperformanceandclinicalfeature(s)known?Moredataneeded.

17.DoesthetaskassessmultipleRDoCconstructsorisitspecifictojustone?Ifitassessesmultipleconstructs,doesitallowforunambiguousconclusionsaboutthetargetedconstruct?Fairlyspecificforcircadianphase.

APPENDIXARS-Il:Summaryofdiscussionofhowwelleachtaskmettheproposedcriteriafortaskevaluation.

Task:Actigraphymeasuredlongitudinally(cosinoranalysis:acrophase,mesor,amplitude)

1.HowstrongistheevidencethatthetaskprovidesavalidmeasureoftheRDoCconstruct?Fairlystrongbasedonactivitypattern.

2.Howgoodistheevidenceaboutthepsychometricscharacteristicsofthetask(e.g.,internalreliability,testretest,floorandceilingeffects,practiceeffects,availabilityofalternateforms,longitudinalstability)?Needsoptimization.

4.Towhatextentisthetask(ordifferentversionsofthetask)suitableforuseacrosslab-basedstudies,clinicaltrials(asameasureoftargetengagementorclinicaloutcome),and/orhigh-throughputscreeningsettings?Easilyusedinclinicalresearch,canbeusedforlargepopulationbasedstudies.

5.Isthetaskfreefromfloor/ceilingeffectssothatitcanbeusedacrossindividualswiththefullrangeofperformance/impairmentonthetasks?Flooreffectifsubjectsdonotmovearoundmuch.

8.Isthetasksuitableforuseinhumansubjectsinavarietyoflabenvironments?Isthetaskfeasibleforadministrationacrosssites?Whatworkisneededtomakethetaskreadyforuseinclinicaltrials?Morenormativedata.Moreanalytictoolstobetteranalyzeactivitydata(e.g.,functionaldataanalysisapproach).

9.Areadequatenormativedataavailableacrossage,gender,education,ethnicity,SES?Moreneeded.

10.Isthetaskcurrentlyinwideusageorhasitsusebeenlimitedtoafewresearchgroups?Fairlycommonlyusedincircadianresearch.

12.Canthetaskbeusedwithmethodstointerrogatebraincircuitry(e.g.,fMRI,EEG,etc.)?N/A

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.

APPENDIXARS-Im:Summaryofdiscussionofhowwelleachtaskmettheproposedcriteriafortaskevaluation.

Task:MunichChronotypeQuestionnaire

1.HowstrongistheevidencethatthetaskprovidesavalidmeasureoftheRDoCconstruct?Measureschronotype.IncontrasttothemorewidelyusedMEQ,whichisbasedonself-reportedpreferencesforsleepschedule,thisquestionnairedetermineschronotypebasedonreportedsleepschedules.

2.Howgoodistheevidenceaboutthepsychometricscharacteristicsofthetask(e.g.,internalreliability,testretest,floorandceilingeffects,practiceeffects,availabilityofalternateforms,longitudinalstability)?Hassomelimitations,suchasthatitisnotaccurateforindividualswhousealarmclockstoawakenondaysofffromwork.Notvalidatedinshiftworkers.

4.Towhatextentisthetask(ordifferentversionsofthetask)suitableforuseacrosslab-basedstudies,clinicaltrials(asameasureoftargetengagementorclinicaloutcome),and/orhigh-throughputscreeningsettings?Maybeusedinallthesesituations.

6.Canthetaskbeused(oradaptedforuse)withchildrenandotherspecialpopulations?Canitbeusedacrossagegroups?Canitbeusedacrossdifferentculturalsettings?Yes,althoughsocioculturalfactorscanaffectresults.Pediatricversionavailable.

8.Isthetasksuitableforuseinhumansubjectsinavarietyoflabenvironments?Isthetaskfeasibleforadministrationacrosssites?Whatworkisneededtomakethetaskreadyforuseinclinicaltrials?Maybeusedinthesesettings;morenormativedataneeded.

9.Areadequatenormativedataavailableacrossage,gender,education,ethnicity,SES?No,moreneeded.

10.Isthetaskcurrentlyinwideusageorhasitsusebeenlimitedtoafewresearchgroups?LesswidelyusedthantheMEQ.

11.Isthetasksensitivetowithin-personchange?Notgenerallyusedforthispurpose;chronotypeatraitmarker.

13.Canthetask(oritsanalog)beusedinanimals?Isananimalversionavailable?N/A

14.Aretherelationshipsbetweentaskperformanceandneuralsignal(s)known?Notspecificallystudied.

16.Isthetaskfreelydistributed(i.e.,notcopyrighted)?Yes,maybedownloadedbutwebsiteasksthatpermissionforuseberequested;nochargeindicated.

17.DoesthetaskassessmultipleRDoCconstructsorisitspecifictojustone?Ifitassessesmultipleconstructs,doesitallowforunambiguousconclusionsaboutthetargetedconstruct?Assesseschronotype.

APPENDIXARS-In:Summaryofdiscussionofhowwelleachtaskmettheproposedcriteriafortaskevaluation.

Task:HorneandOstbergMorningness-EveningnessQuestionnaire(MEQ)

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.

6.Canthetaskbeused(oradaptedforuse)withchildrenandotherspecialpopulations?Canitbeusedacrossagegroups?Canitbeusedacrossdifferentculturalsettings?Hasbeentranslatedintoseverallanguagesandapediatricversionisavailable.

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

13.Canthetask(oritsanalog)beusedinanimals?Isananimalversionavailable?N/A

14.Aretherelationshipsbetweentaskperformanceandneuralsignal(s)known?N/A

15.Aretherelationshipsbetweentaskperformanceandclinicalfeature(s)known?Correlatedwithbiologicalmarkersofcircadianphase.

17.DoesthetaskassessmultipleRDoCconstructsorisitspecifictojustone?Ifitassessesmultipleconstructs,doesitallowforunambiguousconclusionsaboutthetargetedconstruct?Specificforchronotype.

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.

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.

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:

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.

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:

§ 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

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

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

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

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

APPENDIXD:WORKGROUPAGENDA

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