Predictors Of A Differential Neural Response To Infant Cues In Substance Using And Non-Using Mothers

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1 Yale University EliScholar A Digital Platform for Scholarly Publishing at Yale Yale Medicine Thesis Digital Library School of Medicine January 2012 Predictors Of A Differential Neural Response To Infant Cues In Substance Using And Non-Using Mothers Marjorie-Anne Guerra Yale School of Medicine, marjorie.guerra@yale.edu Follow this and additional works at: Recommended Citation Guerra, Marjorie-Anne, "Predictors Of A Differential Neural Response To Infant Cues In Substance Using And Non-Using Mothers" (2012). Yale Medicine Thesis Digital Library This Open Access Thesis is brought to you for free and open access by the School of Medicine at EliScholar A Digital Platform for Scholarly Publishing at Yale. It has been accepted for inclusion in Yale Medicine Thesis Digital Library by an authorized administrator of EliScholar A Digital Platform for Scholarly Publishing at Yale. For more information, please contact elischolar@yale.edu.

2 PredictorsofaDifferentialNeuralResponsetoInfantCues insubstanceusingandnon:usingmothers AThesisSubmittedtothe YaleUniversitySchoolofMedicine InPartialFulfillmentoftheRequirementforthe DegreeofDoctorofMedicine ByMarjorie:AnneRitumbanGuerra 2012

3 Abstract PREDICTORSOFADIFFERENTIALNEURALRESPONSETOINFANTCUESIN SUBSTANCEUSINGANDNON:USINGMOTHERS.""Marjorie*Anne"R."Guerra,"Helena"J.V." Rutherford,"Linda"C."Mayes."Child"Study"Center,"Yale"University"School"of"Medicine," New"Haven,"CT." " Substanceuseduringpregnancyandthepostpartumperiodimpactsnotonly thesubstanceusingmother,butalsoherinfantbyaffectingthemother sabilityto providecareduringthiscriticaltimeperiod.currentresearchdemonstratesthe neuralcircuitryoftherewardandstresssystemsimportantinparentingoverlaps withthecircuitrydysregulatedinaddictiveprocesses,whichmaycompromisea mother sabilitytorespondappropriatelytoinfantcues.intheinitialstudy,parental sensitivitytoinfantcueswasexaminedinsubstanceusingandnon:usingmothers. Participantsviewedimagesofinfantfaceswhilesimultaneous electroencephalography(eeg)recordedtheirneuralresponses.eegdatashowed thatthelatencyoftheface:specificn170event:relatedpotential(erp)peakedlater insubstanceusingmothersrelativetonon:usingmothers,butnodifferencewas observedintheearlierp1erpcomponent,amarkerofgeneralvisualprocessing. Thepresentstudyinvestigatedpredictorsofthisdifferentialneuralresponseto infantfacesbyanalyzingself:reportedmeasuresofbehavioralmotivationsystems (BehavioralInhibitionSystem/BehavioralActivationSystemScale),impulsivity (BarrattImpulsivenessScale:11),andparentingstress(ParentingStressIndex: ShortForm).Itwashypothesizedthatcomparedtonon:usingmothers,substance usingmotherswouldscorehigherinmeasuresofthebehavioralactivation motivationsystem,impulsivity,andparentalstress,andwouldscorelowerin

4 measuresofthebehavioralinhibitionmotivationsystem,andthatthesescores wouldcorrelatewithalaterlatencyofthen170.resultsshowedthatsubstance usingmothersscoredhigherinmeasuresofimpulsivity,behavioralactivation motivationsystemsensitivity,andonemeasureofparentalstress.resultsshowed thatalatern170latencycorrelatedwithahigherfun:seekingscoreofthe behavioralactivationmotivationsystem(pearson sr=.274,p<.05),ahigherscore ofthecognitivecomplexityfactorofimpulsivity(pearson sr=.260,p=.06),anda higherscoreofparentaldistress(pearson sr=.253,p=.09).takentogether,these resultssuggestthatearlyvisualprocessingofinfantfacesmaybecompromisedin motherswithhigherbasfun:seekingsensitivity,higherimpulsivityrelatedto cognitivecomplexity,andhigherparentaldistress.giventhatthesetraitsaremore likelytobefoundinsubstanceusers,theseresultslendfurthersuggestiveevidence tothehypothesisthatparentingcanbecompromisedinaddictivestatesduetoan impairmentinrewardsensitivityandstressreactivitytoinfantcues.

5 Acknowledgements IamenormouslygratefultoDr.LindaMayes,myfacultyadvisor,for generouslysupportingmyresearchinchildpsychiatry,andforconstantlyservingas asourceofunparalleledguidance,encouragement,andinspiration.iwouldalsolike toextendmygratitudetodr.helenarutherford,whonotonlylaidthefoundation forthisthesis,butalsoprovidedtremendousguidanceandsupportthroughouteach stepoftheprocess,andmadewritingathesisnotnearlyasdauntingasiinitially imagined.thankyoutoboththeyalechildstudycenterandtheofficeofstudent Research,whogenerouslysupportedmyparticipationinresearch.Iwouldalsolike tothankmyfriends,whohavesupportedmethroughoutmedicalschoolandthe completionofthisthesis,andkeptmylifebalancedthroughouttheprocess.last, butnotleast,iwouldliketothankmyfamily,whoseunconditionalloveisbeyond words,andwithoutwhomnoneofthiswouldbepossible.

6 TableofContents 1. Introduction Therewardingexperienceofmotherhood Effectsofsubstanceuseontherewardneuralcircuitryofthebrain Adaptationsofthestresssysteminmotherhood Effectsofsubstanceuseonthestressneuralcircuitryofthebrain Assessingmaternalsensitivitytoinfantcuesusing electrophysiology:then Compromisedparentinginaddictiveprocesses StatementofPurpose Methods Participants ApparatusandStimuli Design Self:ReportMeasures DataAnalysis Results CatchTrialResponse ERPDataforInfantFaces Self:ReportMeasuresandCorrelationswithERPData Discussion BehavioralMotivationSystems Impulsivity Stress LimitationsandConsiderations Conclusion References FiguresandTables 48

7 1 Introduction Thetransitiontomotherhood,includingthedevelopmentofsensitivityto infantcuesandmaternalbehaviors,iscrucialforboththeimmediatecareofthe infantandthelong:termdevelopmentofthechild,includingcognitivedevelopment (1),stressreactivity(2),andfuturematernalcare(2,3).Thistransitioninvolves significantpsychologicalandneurobiologicalchanges.specifically,adaptationsin theneuralcircuitrymediatingrewardandstressappeartoaffectamother sability torespondappropriatelytoinfantcues(4).thesepathwaysoverlapwiththeneural pathwaysthataredysregulatedintheaddictedstate(5).thecurrentstudywaspart ofalargerstudybyrutherfordetal.(6),inwhichadifferentialbrainresponseas measuredbyelectroencephalography(eeg)wasfoundinresponsetovisualinfant cuesinsubstanceusingmothersrelativetonon:usingmothers.thepurposeofthis thesiswastoinvestigatewhetherthisdifferentialsensitivitytovisualinfantcues wasassociatedwithdifferencesinmeasuresofbehavioralmotivation,impulsivity andparentalstress. The"rewarding"experience"of"motherhood" Althoughparenthoodisademandingrole,itisalsoapotentiallyintensely satisfyingexperienceasevidencedbyactivationofkeyrewardpathwaysinthe brain.theneuralcircuitryunderlyingtherewardsystemincludesthepathways connectingtheventraltegmentalarea(vta)ofthemidbrainwiththenucleus accumbens(nac)andprefrontalcortex(pfc),withdopamineservingasthemajor

8 2 neurotransmittermediatingthesepathways(5).inpreclinicalmodels,pupsuckling hasbeenfoundtoactivatethesedopaminergicrewardpathwaysindams(7). Similarly,fMRIstudiesoffirst:timehumanmothersshowedactivationoftheVTA, striatum,andfrontallobewhenviewingimagesoftheirowninfant sfacessmiling butnotcrying(8).therewardassociatedwithinfantcuesandmaternalbehavior mayinfactserveanimportantadaptivefunction,asitmotivatesinitiationand maintenanceofmaternalbehaviors. Asaresult,amothermustbeabletoappropriatelygaugetherewarding valueofastimulus,acognitivefunctionthatismediatedbythevta(5).inrodents, pharmacologicalinactivationofthevtaresultsindeficitsinmaternalbehaviors(9). TheVTAisalsoanimportantsourceofdopamine,withprojectionstotheNAcand PFC.Inlactatingrats,puplickingandgroomingisassociatedwithsignificantly increaseddopamineinthenac(10).interestingly,theincreasedsignalwasnoted priortotheonsetofthebehaviorandtheconcentrationofdopaminecorrelated directlywithdurationofthebehavior,suggestingtheimportanceofthe dopaminergicsignalinmediatingthemotivationofthebehavior. ThePFCservesavarietyofcognitivefunctions,suchasmotivation,self: control,decision:making,goal:orientedactivity,workingmemory,andattention shifting(10,11),andthuscaninfluencematernalbehavioronanumberoflevels.in rats,disruptionstothepfccausedeficitsinsomematernalbehaviorsanda disorganizationofthepatternofmaternalbehavior(12),whichmaybeexplainedin partbyimpairmentsinmotivationandworkingmemory,respectively.infunctional

9 3 magneticresonanceimagingstudiesofhumanmothers,theorbitofrontalcortex (OFC)wasactivatedbilaterallywhenviewingpicturesofinfants,withactivation correlatingwithpleasantmoodscores(13).thissuggeststheroleoftheofcin mediatingsensitivitytoinfantcues,whichisfurtherinfluencedbymaternal characteristicssuchasmood. Importantly,themedialPFCandOFChavebothbeenshowntobeimportant mediatorsofimpulsivity(14),withdopamineservingasamajorneurotransmitter (15).Arecentpreclinicalstudysuggeststhatimpulsivityindeedaffectsmaternal behavior,asratsthatdemonstratedhigherlevelsofimpulsivityonefficiencytasks spentlesstimeonmaternalbehaviors(16).impulsivityhasbeendefinedas predispositiontowardrapid,unplannedreactionstointernalandexternalstimuli withoutregardforthenegativeconsequencesofthesereactionstothemselvesor others (17).Accordingly,impulsivemothersmayacttowardsanon:infantstimulus attheexpenseofthecareofherinfantbecausetheyviewthenon:infantstimulusas morerewardingthantheirowninfant. Insummary,thesestudiesindicatetheimportanceoftherewardneural pathwaysinmotivatingmaternalbehaviorandthepotentialforindividual differencesinmediatingthesepathways. Effects"of"substance"use"on"the"reward"neural"circuitry"of"the"brain"

10 4 Theuseofdrugsofabusecontinuestobeasignificantpublichealthissuein theunitedstates.approximately15.6%ofthepopulationparticipatesin nonmedicalorillicitdruguseduringtheirlifetime,andofthisgroup,20.1%will continueontodrugabusewhile18.6%willcontinueontodrugdependence(18).it isimportanttonotethatthepresentstudyisbasedundertheframeworkthat substanceusereflectsanaddictive"processimpactingtherewardandstressneural systemsmoregenerally,leadingtothegradualdevelopmentofhabitualdrug: seekingbehavior. Theacuterewardingeffectsofalldrugsofabuseappeartobemediatedby themesolimbicpathways.inonestudyusingbraindialysisinrats,itwasfoundthat opiates,ethanol,nicotine,amphetamine,andcocaineallincreasedextracellular dopamineconcentrationsintheseptiofthenucleusaccumbens(19).currently,itis thoughtthattheacuterewardingeffectofdrugsofabusearemediatedinvarious mannersinvolvingthemesolimbicpathways:cocaine,amphetamine,andnicotine throughdopaminereleaseinthenac;opiatesthroughopioidpeptidereceptor activationinthevtaandnac;andalcoholthroughthenacandamygdala(5).in addition,reinforcementofdrug:seekingbehaviorappearstobemediatedbythe mesolimbicsystemincocaineandamphetamines,thoughthisisnotnecessarilytrue inotherdrugsofabusesuchasheroinorethanol(5). ThePFCisalsodisruptedinaddiction,leadingtodeficitsinimportant executivefunctionssuchasmotivationandself:control.intheaddictedstate, behaviortowardnon:drugstimulimaybedecreasedduetoimpairedsalienceof

11 5 thesestimuli.inastudybygoldsteinandcolleagues(20),thesensitivitytorelative monetaryvaluewasassessedincocaine:addictedindividualsbypresentingthem withagradientofmonetaryrewards,rangingfrom$10:$1000.interestingly,over halfofthecocaine:addictedsubjectsvaluedallmonetaryamountsequally,andthis responsewasassociatedwithhigheractivationsinthelateralofcandfrontalgyrus andloweractivationsinthemiddlefrontalgyruswhencomparedtothecocaine: addictedparticipantswhodidnotshowthisimpairedvaluation.thisfinding suggestedthataddictedindividualshaveanimpairedabilitytojudgethevalueof non:drugstimuli,whichmaybeduetoimpairedrewardsalienceofthestimuliwhen comparedtodrugsofabuse.additionally,theimagingfindingssuggestedthatthis deficitwasassociatedwithadifferentialactivationofthepfc. Furthermore,thePFCisinvolvedinself:control,whichisimpairedin addictiveprocesses.basedonneuroimagingstudiesoverthepast10years, GoldsteinandVolkow(11)proposethataddictionleadstoanimpairedabilityof higherordercognitiveinputfromthepfctoinhibitmaladaptivebehavior,leading tounregulateddrug:seekingbehavior.onabehaviorallevel,theacuterewarding effectoftakingthedrugleadstopositivereinforcementofdrug:seekingbehavior, eventuallyleadingtoimpulsivitytoacquireandusethesubstance(5).individuals withahistoryofdrugdependenceindeedshowhigherlevelsofimpulsivitybased onbothbehavioralandself:reportmeasures(21). Addictiveprocessesleadtodysregulationoftherewardneuralcircuitry,as describedabove,whichcanthenleadtoimbalancesinbehavioralmotivation

12 6 systems.twokeybehavioralmotivationsystemsincludethebehavioralactivation system(bas)andthebehavioralinhibitionsystem(bis),whichwereproposedto underlietwodimensionsofpersonality:impulsivityandanxiety,respectively(22). TheBAS,alsoknownastheappetitivesystem,activatesbehaviorthatleadsto rewardingstimuli,withincreasedbassensitivitybelievedtounderscore impulsivity.inaddictiveprocesses,theindividualhasahighersensitivitytothis motivationalsystem,withtheacuterewardingeffectofthedrugservingasthe incentive.thismayoccurattheexpenseofthesalienceofothernormallyrewarding stimuli,suchasinfantcues.thebehavioralinhibitionsystem(bis),alsoknownas theaversivemotivationsystem,inhibitsbehaviorthatleadstonegativeoutcomes. Inaddictiveprocesses,theindividualhaslesssensitivitytothismotivationalsystem actingsolelywithdrugsinmindandwithoutconsideringthenegativemedicaland socialconsequences. Insummary,theabovefindingssuggestthataddictiveprocessesleadtoa dysregulationoftherewardneuralcircuitry,leadingtochangesinthebehavioral motivationsystemsnowdrivenprimarilybytheacuterewardingpropertiesof substanceuse. Adaptations"of"the"stress"system"in"motherhood" Althoughmotherhoodhasrewardingproperties,pregnancyandthe postpartumcanbestressfulperiodsforthemother,withdirectandindirect implicationsfortheinfant.gestationalstresshasbeenshowntodirectlyaffect

13 7 stressreactivityandfuturematernalcareoflactatingfemaleoffspring(23). Additionally,alterationsinthestresssystemcanindirectlyaffecttheinfantdueto impairedmaternalcare.prenatalstresshasbeenshowntonegativelyimpact maternalbehaviors(24:26),highlightingtheimportanceofmaintainingahealthy amountofstressduringtheperipartumperiod. Thephysiologicalexperienceofstressismediatedbythehypothalamic: pituitary:adrenal(hpa)axis.inresponsetoanacutestressor,theparvoventricular nucleusofthehypothalamussecretescorticotropin:releasingfactor(crf)intothe hypophysealbloodsupply,whichactsontheanteriorpituitaryglandtosecrete adrenocorticotropichormone(acth)intothebloodsupply,eventuallyreachingthe adrenalmedullawhichsystemicallyreleasesglucocorticoids,namelycorticosterone inratsandcortisolinhumans(27).thisinturnleadstophysiologicalresponsesin thecardiovascular,autonomic,metabolic,neural,andimmunesystems(28).the systemisregulatedbynegativefeedbackinducedbytheglucocorticoidsactingon thepituitary,hypothalamus,andhippocampus. Throughoutpregnancyandthepostpartumperiod,neuroendocrineand neurobiologicaladaptationstakeplaceleadingtoadifferentialsensitivityto stressorsinmothers.pregnancyandlactationarecharacterizedbyhigherbasal glucocorticoidlevels,decreasedhormonal(specifically,hormonesofthehpaaxis) andemotionalresponsestostressors,andanincreasedsenseofcalmness(29). Oxytocinplaysanimportantroleduringtheperipartumperiodinpartuitionand lactation,andemergingdatasupportsitsroleinmediatingthisadaptationinthe

14 8 stresssystem(29).bothcrfandoxytocinaresecretedbytheparaventricular nucleusofthehypothalamus,andoxytocinhasbeenshowntodecreasecrfmrna expression(30).infact,inpreclinicalmodels,oxytocinhasbeenshowntoreduce theincreaseinbloodpressurecausedbyprenatalstress(31). Themodificationofthestresssysteminthetransitiontoparenthoodis critical.infantcuessuchascriesmayprovidemorestressthananindividualwould otherwisebecapableofhandling.administrationofcorticosteroneduring pregnancyandthepostpartumresultsinimpairedmaternalbehaviorsindams, suchasreducedtimespentonnursingandnesting(32).thisfindingsuggeststhat hyperactivityofthehpaaxismayrepresentanunmanageablestressloadthat impairsamother sabilitytocareforherinfant.atthesametime,componentsofthe HPAaxisareimportantinmodulatingmaternalbehavior.CRFsignalinghasbeen showntoplayaroleinmaternaldefensebehavior(33),asstressfulcuesfroma foreignintruderactivateabehavioralresponsetoprotectherpups.thishighlights theimportanceofpreciseregulationofthestresssystem,asamothermust appropriatelyjudgethestressfulnessofcuesinprovidingcaretoherinfant. Insummary,pregnancyandthepostpartumrepresentadynamictimeforthe stressneuralpathways,whichmakeitvulnerabletoinfluencesofmotherhoodand, potentially,otherexternalfactors. Effects"of"substance"use"on"the"stress"neural"circuitry"of"the"brain"

15 9 Thestresssystemhasbeenimplicatedinthevariousstagesofdruguseand addiction.inpreclinicalmodels,acutecocaineadministrationhasbeenshownto increaseplasmaacthandglucocorticoids,whichappearstobemediatedby cocaine:inducedreleaseofcrhfromthehypothalamus(27).inpregnantrats, chroniccocaineadministrationleadstosignificantlyhigherlevelsofcorticosterone (34). Stressplaysseveralrolesinthecyclicprocessofaddiction,havingeffectson bothdrugabuseandrelapse(35).koobandvolkow(5)proposethatstressserves asnegativereinforcementduringwithdrawal,asthehpaaxisisactivatedduring withdrawalfromallmajordrugsofabuse.astudyinmaleratsshowedthat conditionedplaceaversiontoopiatewithdrawalcanbereversedbyacrf:1 receptorantagonist(36),suggestingtheroleofcrfinmediatingtheeffectofacute withdrawal.theroleofthestresssystemhasalsobeenimplicatedinrelapse. Psychologicalstressmotivatescravingsincocaineabusers(37),aneffectthat appearstobemediatedcrfactingonextrahypothalamicstresspathwayssuchas theamygdala(5,38,39). Ithasbeenproposedthattheeffectsofsubstanceuseonstressneural circuitrycanleadtoamaladaptivestressresponsethatperpetuatesregulardrug abuseand,importantly,alterssensitivitytostressors(35).motherswhoused cocaineduringpregnancyreportedmorelifestressandlesssenseofcontrol(40), thoughtherelationshipbetweenstressandsubstanceuseislikelybi:directional.in onestudy,recentlyabstinentcocaine:dependentindividualsshowedahigher

16 10 sensitivitytonegativeemotionsandincreasedphysiologicalmarkersofstressin responsetostressfulvisualcueswhencomparedtosocialdrinkers(41).this providessomeevidencetowardsanenhancedreactivitytostressfulstimuliin substanceusingindividuals,atleastintheabstinentphaseofaddiction. Insummary,theabovefindingssuggestthataddictiveprocessesleadtoa dysregulationofthestressneuralcircuitry,leadingtoamaladaptivestressresponse withalteredreactivitytostressfulcues. Assessing"maternal"sensitivity"to"infant"faces"using"electrophysiology:"the"N170" Becauseinfantfacesmayserveasimportantcuesformotivatingmaternal behaviors(8),perceptionofinfantfacesisakeycognitivefunctioninparenting.the N170ERPcomponenthasbeenidentifiedasanearlymarkeroffaceprocessing, observedinresponsetohumanfacestimulibutnotinresponsetofacesofanimals, humanhands,andotherinanimateobjects(42).specifically,then170reflects structuralencodingoffaces(43). TheN170ismostprominentovertheoccipito:temporalregionsandislarger ontherighthemispherecomparedtothelefthemisphere(42).ithasbeen correlatedwithareasimplicatedinfaceprocessing,suchasthefusiformgyrusand rightmedial,superior,andinferiortemporalgyri(44).usingevidencefrom neuroimagingstudies,acurrentmodelsuggeststhatfaceprocessingisnotsolely limitedtothefusiformgyrus,andmayinfactrepresentaninteractionbetweenthe

17 11 fusiformgyrusandtheamygdala,akeybrainregioninmediatingstress(45).the authorssuggestthispathwayasthemechanismthroughwhichfaceprocessingis enhancedbyemotionalexpressions.then170hasbeenfoundtobeinfluencedby top:downfactors,suchasvisualpriming(46),althoughwhetheritismodulatedby emotionisstillunderdebate(6).arecentmagnetoencephalography(meg)studyin adultssuggeststheroleofkeyrewardbrainregionsingenerationofthen170(47). TheresultsshowactivationofthemedialOFCspecifictoinfantfacesataround130 ms.givenitstimeframe,thismegactivationmaybeanalogoustothen170erp component,andmaysuggesttheroleoftheofcingenerationofthen170. Faceprocessingisanimportantelementofsocialinteractions,and accumulatingevidencesupportsthenotionthatthen170maybeinfluencedby socialfactors.forexample,then170hasbeenshowntodifferentiateindividuals withautisticspectrumdisorderfromthosewithnormalsocialdevelopment(48) andextrovertedindividualsfromintrovertedindividuals(49).giventhepotentially intensesocialinteractionbetweenmotherandinfant,recentstudieshavestartedto examinethen170ofmothersinresponsetoinfantfaces.ofnote,thesefewstudies haveprimarilylookedatitseffectonn170amplitude,notlatency. ArecentstudysuggeststhattheN170mayinfactbemodulatedbybond formation(50).inthisstudy,itwasfoundthatwhenviewingimagesofunfamiliar infantfaces,then170amplitudewasenhancedinnewparentsandnewromantic partnersrelativetoromanticallyunattachedsingles,suggestingthatthetransition toparenthoodstrengthenstheneuralcircuitryinvolvedinprocessinginfantcues

18 12 thatmotivateparentalbehaviors.thisisparticularlyrelevanttosubstanceusing mothers,asparentalsubstanceusehasbeenshowntonegativelyimpacttheparent: childattachmentrelationship(51). Inasampleofmothers,differencesintheN170wereobservedbetween thosewhowereneglectfulandthosewhowerenon:neglectful(52).specifically, whileviewingimagesofinfantscrying,laughing,orwithaneutralexpression,non: neglectfulmothershadthemostenhancedn170amplitudeinresponsetothecry imageswhencomparedtothelaughterorneutralimages.thisdifferentiationwas notobservedinneglectfulmothers.theauthorsofthisstudyinterprettheseresults tosuggestthatneglectfulmothersmaynotfindthesamerewardsalienceinvisual infantcuesasnon:neglectfulmothers,andthismayultimatelyunderliethe impairedinteractionbetweenneglectfulmothersandtheirchildren. Insummary,thesefindingssuggestthattheN170generatedinresponseto infantfacesmaybeinfluencedbyindividualdifferencesinsensitivitytoinfantcues. " Compromised"parenting"in"addictive"processes" Maternalsubstanceusecanhavedetrimental,ifnotdevastating consequencesforboththemotherandherinfant.ithaslongbeenrecognizedthat maternalsubstanceabuseincreasestheriskofimpairedparentingskills(53),andin fact,ithasbeenassociatedwithincreasedratesofchildneglect(54)andchildabuse (55).Interactionswithinfantsarealsoimpaired.Inonestudy,cocaine:using

19 13 motherswerefoundtobelessresponsivetoandlessinteractivewiththeirinfants (56).Ratsexposedtobothnicotineandethanolduringpregnancywerefoundto havesimilarimpairedinteractionswiththeirpups(57).giventheeffectsof substanceuseontherewardandstressneuralcircuitry,parentingmaybe compromisedinaddictiveprocessesduetoadecreasedrewardsensitivityand enhancedstressreactivitytoinfantcues,leadingtoadeficitinmaternalbehaviors thatarerequiredforthepropercareanddevelopmentoftheinfant. Preclinicalstudiessupporttheideathatsubstanceusemaydirectlyaffecta mother sresponsetobothrewardingandstressfulstimuli.usingfunctional magneticresonanceimaginginrodents,itwasfoundthattheactivationofthe dopaminergicrewardsysteminresponsetonursingwasattenuatedwhendams wereexposedtococainebeforepregnancy(58).thisstudyhighlightstheimpact substancesmayhaveontherewardingpropertiesofmaternalbehavior. Additionally,ratsexposedtococainepostpartumshowmoreaggressivebehavior, butnon:protectivebehaviortowardstheirpupsinresponsetointruders(59).these damsshowalterationsintheirbehaviortowardstressfulstimulithatnegatively impactthecareoftheirpups.inhumanmothers,arecentstudybylandiand colleagues(60),usingfunctionalmagneticresonanceimagingshowedthat substanceusingmothershadlessactivationinthepfcandlimbicregionswhen comparednon:usingmothersinresponsetobothinfantfacesandcries.thisstudy providesevidenceforadifferentialresponsetoinfantcuesinsubstanceusing mothersinareasassociatedwithmotivationandreward,whichmaybedueto dysregulationintherewardandstressneuralpathways.

20 14 Thus,substanceusingmothersappeartodisplayadifferentialsensitivityto rewardingandstressfulstimuli.intheinitialstudy,rutherfordetal.(6)explored whetherthiseffectwasmanifestedasadifferentialsensitivitytoinfantcuesby investigatingtheprocessingofinfantfacesusingelectroencephalography(eeg). Twospecificevent:relatedpotentials(ERP)wereexaminedwithregardtoface processing:(1)n170,anearlymarkeroftheencodingoffacestructure,and(2)p1, anearlymarkerofgeneralvisualprocessing.itwasfoundthatsubstanceuse modulatedthelatencyofthen170,butnotthep1,suggestingthatthisfindingwas specifictofaceprocessingandnotageneralslowingduetosubstanceuse. Inthecurrentstudy,self:reportmeasurescompletedbythesemotherswere analyzedtolookforpredictorsofthisdifferentialneuralresponse.itwas hypothesizedthatsubstance:usingmotherswouldscorehigherinmeasuresof behavioralactivationmotivationsystem,impulsivity,andstressandlowerin measuresofbehavioralinhibitionmotivationsystemrelativetonon:usingmothers, giventheunderlyingdysregulationoftherewardandstressneuralcircuitryin addictiveprocesses.furthermore,itwashypothesizedthatthesescoreswould correlatewithalaterlatencyofthen170,astherewardsalienceofthesubstanceis greaterthanthatoftheinfantcuesinthesesubstanceusingmothers,leadingto decreasedmotivationtowardstheprocessingofinfantfaces. StatementofPurpose Specific"Aims"

21 15 Tofurtherelucidatetherelationshipbetweenaddictiveprocessesonthe neuralcorrelatesofparenting,includingmaternalsensitivitytovisualand auditoryinfantcues. Todeterminethepredictorsofthedifferentialneuralresponsetovisual infantcuesinsubstanceusingandnon:usingmothers. Specific"Hypotheses" Substanceusingmotherswillscorehigherinself:reportedmeasuresofthe behavioralactivationmotivationsystem,impulsivity,andparentalstress, andwillscorelowerinthemeasureofthebehavioralinhibitionmotivation systemwhencomparedtonon:substanceusingmothers." ThelatencyoftheN170peakwillpositivelycorrelatewithscoresofthe behavioralactivationmotivationsystem,impulsivity,andparentalstressand inverselycorrelatewithscoresofthebehavioralinhibitionmotivation system." Methods Participants" Atotalof79motherswererecruitedfromtheNewHavencommunity throughdrugtreatmentandrehabilitationcenters,postpartummaternitywards, andflyerspostedthroughoutthecommunity.informedconsentwasobtainedfrom

22 16 allparticipants.thepresentstudywaspartofalargerstudythataimedto investigatetheeffectofsubstanceuseontheneuralcorrelatesofparenting. Inordertodeterminesubstanceusestatus,acombinationofself:reportdata andurinetoxicologywerecollectedattheintakeapproximatelythreemonthspost: partum.motherswereclassifiedassubstanceusingiftheyusedanydrugsoralcohol regularlyduringpregnancyorthepostpartumperiod(n=22).substancesusedby thesemothersincludedtobacco,marijuana,heroin,amphetamines,methadone, alcohol,cocaine,opiates,orothersubstancesnotdisclosed.moredetailsofthe determinationofsubstanceusestatuscanbefoundinthemanuscriptbylandietal (60).SeeTable1forcompletebreakdownofsubstancesused. Themeanageinyearsofsubstanceusingmothersincludedinthefinal analysiswas26.82(sd=5.66),whilethemeanageinyearsofnon:substanceusing motherswas29.37(sd=6.74).bothhadameannumberofchildrenof2,witha rangeof1:6children.fifty:fivepercent(55%)ofsubstance:usingmothersand38% ofnon:substanceusingmotherswereafrican:american;and23%and46% respectivelywerecaucasian.themajorityofsubstanceusingmothersreportedthat theyweresingle(73%)followedbydivorced(14%).themajorityofnon:substance usingmothersweresingle(50%)followedbymarried(47%).therewasa significantdifferenceinmaritalstatusbetweensubstanceusingandnon:using mothers(χ2=11.48,df=53,p<.01).therewasalsoasignificantdifferenceinthe meanyearsofeducationbetweengroups,asnon:substanceusingmothershadmore yearsofeducation(15.48,sd=4.04)relativetonon:usingmothers(11.54,sd=2.00)

23 17 (t(45)=4.28,p<.001).seetable2forcompletebreakdownofdemographic information,includingeitherat:testorchi:squareanalysisfordifferencesbetween substanceusingandnon:usinggroups. Apparatus"and"Stimuli" TomeasureEEG,a128:electrodechannelgeodesicsensornet(Electrical GeodesicsIncorporated)(61)wasplacedontheparticipant sheadandfitted accordingtomanufacturespecifications,withelectrodesspacedevenlyand symmetricallyacrossthescalp.eegwasrecordedcontinuouslyat250:hzusing NetStation4.2.1withhighimpedanceamplifiers(0.1Hzhighpass,100Hzlowpass). ElectrodeswerereferencedtoCzduringEEGrecording.Impedanceswerekept below40kω.inordertoinvestigateneuralresponsestobothvisualandauditory infantcues,bothtypesofstimuliwerepresentedtothemothersduringthetrials,as describedbelow. Visualstimuli.VisualstimuliwerepresentedonaPentium:IVcomputer controllinga51cmcolormonitor(75hz,1024x768resolution)runninge:prime 1.2software(62).Facestimuliwereviewedatadistanceofapproximately70cmin asound:attenuatedroomwithlowambientillumination.visualstimuliwere comprisedofphotographsofinfantfacesbetweentheagesoffiveandtenmonths adaptedfrompreviouswork(63).atotalof126imageswereused,withtwenty:one differentimagesfromsixinfants.theseimageswerebalancedforgenderandrace (CaucasianandAfrican:American)andwereunfamiliartotheparticipants.The

24 18 infantfaceswerepresentedonablackbackgroundandmeasured,onaverage,7.63 by8.07 (9.32cmby9.88cm).Theinfantfacesdisplayedhappy,neutral,andsad affectstates,asratedbyanindependentgroupof11participants.inorderto evaluateperceivedaffectlevel,facestimuliwereratedonascaleof1(happy)to10 (distressed).arepeatedmeasuresanovaoftheinfantfaceratingonthethree emotions(happy,neutral,sad)wassignificant[f(2,20)=146.43,p<0.001].pairwise comparisonsshowedthathappyfaces(m=2.19,se=0.24)wereratedassignificantly lessdistressed(meandifference=:1.55,se=0.37,p<0.01)thanneutralfaces(m=3.74, SE=0.43),whichwereratedassignificantlylessdistressed(Meandifference=:4.16, SE=0.41,p<0.001)thansadfaces(M=7.90,SE=0.11). " Design" Trialsconsistedofcentrallypresentedfixationcross,followedbythe stimulus,andthenablankscreen.visualstimuli(infantfaces)werepresentedfor 300msandauditorystimuli(infantcriesorneutraltone)werepresentedfor2000 ms.inordertoavoidexpectancyeffectsofstimulusonset,theinter:trialinterval wasvariedduringboththefixationcrossandblankscreen,rangingfrom1400:2000 ms.eachparticipantunderwentsevenblocksof42trials,witheachblockcontaining 21infantfacepresentationsand21auditorypresentationsthatwerequasi: randomlypresented,foratotalof252experimentaltrials.theorderofpresentation wasthesameforeachparticipant.therewere126totalvisualstimulitrials,42 trialsforeachofthehappy,sad,andneutralconditions.therewere126total

25 19 auditorystimulitrials,42trialsforhighdistress,44trialsforlowdistress,and40 trialsfortheneutraltone. Inordertoensurethatparticipantskepttheirattentiontopresentationof thestimuli,aone:backmemorytaskwasincludedthroughoutthecourseofthe experiment.duringthesetrials,aquestionmarkreplacedthefixationcrossto indicatetheimpendingmemorytask.participantswereaskedtoindicatewhether theproceedingstimuluswasthesameordifferenttothenextonepresented,and communicatedtheirresponseusingabuttonbox.thesecatchtrialswerenot includedintheanalysis.therewereanequalnumberofcatchtrialsinwhichthe stimuluswasthesameanddifferentastheprecedingone.thesecatchtrials accountedforanadditional42trialsintheexperimentforagrandtotalof294 experimentalandcatchtrials. Priortothesetrials,eachparticipantunderwenteightpracticetrialsto familiarizeherselfwiththeprocedure.overall,theexperimentwascompletedin approximately30minutes. Self*Report"Measures" AftercompletingtheEEGportionofthestudy,participantscompleted questionnairestoassessdemographicsandbehavioralqualities.participants completedthebarrattimpulsivenessscale:11,thebehavioralinhibitionsystem/

26 20 BehavioralActivationSystemScale,andtheParentingStressIndex:ShortForm. Eachquestionnaireisdescribedbelow. BehavioralInhibitionSystem/BehavioralActivationSystemScale(BIS/BAS)(65). TheBIS/BASscaleisa24:itemself:reportmeasurethatisdesignedtoassessthe sensitivityofanindividual saversiveandappetitivemotivationsystems.thisscale isbasedonatheoryproposedbygray(22),whopostulatedthattheaversiveand appetitivemotivationsystemsunderlietwodimensionsofpersonality:anxietyand impulsivity,respectively.theaversivemotivationsystem,alsoknownasthe behavioralinhibitionsystem,inhibitsbehaviorthatcouldleadtounpleasantor negativeoutcomes.theappetitivesystem,alsoknownasthebehavioralactivation system,activatesbehaviorthatcouldleadtopleasantorrewardingoutcomes.the scalemeasuresthreedistinctbutrelatedcomponentsofthebas,includingdrive, fun:seeking,andresponsivenesstorewards.thedrivesubscalemeasurespersistent pursuitofdesiredgoals.thefun:seekingsubscalemeasuresawillingnessto spontaneouslyapproachaneventthatispotentiallyrewarding.thereward responsivenesssubscalemeasurespositiveresponsestotheoccurrenceor anticipationofareward. Allitemsaremeasuredonafour:pointLikertscale,where 1 represents verytrueforme and 4 represents veryfalseforme.allitemsexceptitems2 and22arescoredinreverse.ascoreforthebisandeachcomponentofthebasis determinedbythesummationofthescoresofspecificitems,andahigherscore denotesahighersensitivitywithrespecttothatcomponent."

27 21 CarverandWhite(65)reportconvergentanddivergentvalidityoftheir scaleswithmeasuressuchasthepositiveandnegativeaffectschedule,minnesota MultiphasicPersonalityInventory,andEysenckandEysenck sextraversionscale. Theyalsoreportadequateinternalconsistency,withCronbach salpharanging from.66:.74. BarrattImpulsivenessScale:11(BIS:11)(66).TheBIS:11isa30:itemself:report measurethatisdesignedtoassesstheimpulsivityofanindividual.thescaleis basedontheideathatimpulsivityisamulti:dimensionalconstruct.specifically,it assessesthreesecond:orderfactorsofimpulsivityincludingattentional impulsiveness,motorimpulsiveness,andnon:planningimpulsiveness,andsixfirst: orderfactorsofimpulsivityincludingattention,motor,self:control,cognitive complexity,perseverance,andcognitiveinstability." Theitemsaremeasuredonafour:pointLikertscale,where 1 represents Rarely/Never and 4 represents AlmostAlways/Always,withquestions1,7,8, 9,10,12,13,15,20,29,and30scoredinthereverse.Ascoreforeachfactoris determinedbythesummationofthescoresofspecificitems,andahigherscore denotesamoreimpulsiveindividualwithrespecttothatfactor." Pattonandcolleagues(66)reporthighinternalconsistencyoftheBIS:11 amongundergraduates,substanceabusepatients,generalpsychiatricpatients,and prisoninmates,withcronbach salpharangingfrom.79:.83.additionally,thebis:11 showsconvergentvalidityamongotherself:reportmeasuresofimpulsivitysuchas theeysenckimpulsivenessscaleandbehavioralmeasuresofimpulsiveness(67).

28 22 ParentingStressIndex:ShortForm(PSI:SF)(68).ThePSI:SFisa36:itemself:report measurethatisdesignedtoassessstressintherelationshipbetweenparentand child.theindexlooksatparentingstressinthreedomains:parentaldistress, parent:childdysfunctionalinteraction,anddifficultchild.theparentaldistress scoreindicatesthedegreeofpersonalstresssuchasconflictwithaspousethat resultfromthelimitedabilitytofulfillotherroleswhenraisingachild.theparent: childdysfunctionalinteractionscoreindicatesthedegreeofstressfromthe interactionwiththechild.thedifficultchildscoreindicatestheparent sperception ofthechild sinabilitytoregulatehisorherdisruptivebehavior.thepsiwas designedtoidentifydysfunctionalparentingand/orchildbehavior. Theitemsaremeasuredonafive:pointLikertscale,where 1 represents stronglyagreeand 5 represents stronglydisagree.ascoreforeachdomainis determinedbythesummationofthescoresof12specificitems,andahigherscore denotesahigherlevelofstressinthatdomain." TheParentingStressIndexandPSI:SFhavebeenvalidatedagainstmeasures includingthesymptomchecklist:90:revisedandbriefsymptomindex,both measuresofemotionalhealth(68,69).ithasalsobeenshowntohavehigh reliabilityinbothalargelycaucasian,marriedpopulation(68)aswellasalow: income,predominantlyminoritypopulation(69). " Data"Analysis"

29 23 EEGData Pre*processing.TherawEEGdatafromeachparticipantwerepre:processedand preparedforstatisticalanalysisusingnetstation4.2.1.foreachexperimental condition,datafromeachparticipantwereaveraged.a30:hzlow:passfilterwas appliedtodecreaseenvironmentalnoiseartifacts.dataweresegmentedfrom100 msbeforestimulusonsetto900msafterstimulusonset.inordertocontrolforeye blinksandmovements,athresholdof150microvoltswasimplemented.channels withartifactsinmorethan50%ofsegmentsweremarkedasbadchannelsand replacedthroughsplineinterpolation(70).segmentsthatcontainedeyeblinks,eye movement,andthosewithmorethan20badchannelsweremarkedasbadand excludedfromtheanalysis.onaverage12trialsperparticipantwereexcluded. Participantswithlessthan25%remaininggoodtrialswereexcluded(n=19),and sixadditionalparticipantswereexcludedafterexcessivenoisewasnotedonvisual inspection,thathadnotbeenpickedupbypreprocessingprotocols.then170was notdiscernibleforthesesixparticipants.thefinalsampleincluded54participants, comprisedof32non:substanceusingmothersand22substanceusingmothers. Statistical"Analysis.Fortheanalysisoffaceprocessingdata,P1andN170ERPswere assessedat12electrodes:sixelectrodesovertheleftlateralposteriorscalp(58,59, 64,65,69,70)andrightlateralposteriorscalp(90,91,94,95,96),asshownin Figure1.TheseelectrodeswereselectedbasedonthemaximalobservedN170 amplituderesponsetotheinfantfaces.furthermore,theycorrelatewiththescalp

30 24 regionsthatcharacteristicallyelicitthen170(42)andarethesameelectrodesthat havebeenusedtostudythen170inpriorresearchusingdensearrayeeg(48). UsingtheNetStationuserdefinedeventfunction,timewindowsforthe N170andP1werederivedandcustomizedforeachparticipant.Thefunctionallows statisticalextractionofeachcomponenttoberepresentativeofthevariabilityinthe waveforms.forthep1,thetimewindowrangedacrossparticipantsfrom47msto 195ms,andtheP1peakwasdefinedasthemaximumamplitudefallinginthat range.forthen170,thetimewindowrangedacrossparticipantsfrom91msto243 ms,andthen170peakwasdefinedastheminimumamplitudefallinginthatrange. P1andN170datawereaveragedfromelectrodesiteswithintheleft hemisphereandrighthemisphere.statisticalanalysiswasconductedonamplitude andlatencymeasuresforeachseparatecomponent(p1,n170)usingrepeated measuresofanalysisofvariance(anova).specifically,thedatawereanalyzed usingathree(emotionalexpression:happy,neutral,sad)bytwo(hemisphere:left, right)within:subjectsanovawithabetween:groupfactorofsubstanceusingstatus (substanceusing,non:substanceusing).effectsizeispresentedaspartialeta: squared(η 2 partial),where.01representssmalleffectsize,.06representsamedium effectsize,and.14representsalargeeffectsize,consistentwithpreviousstudies (49,71).Whenapplicable,Greenhouse:Geissercorrectionswereused. Self:ReportMeasures

31 25 BIS/BAS"Scale.Questionnairesfrom53participantswerescoredforfivemeasures, includingbissensitivity,basdrive,basfun:seeking,basrewardresponsiveness, andbastotal,byaddingtherespectiveresponsesforeachsubset(65)..onemother wasexcludedforincompletedata.themeanscoreofeachsubsetwasdetermined forthreegroups:allparticipants(n=53),substanceusingmothersonly(n=21),and non:substanceusingmothersonly(n=32).thedataforeachofthesethreegroups werefurthertestedfornormalityusingthekolmogorov:smirnovtest. BIS*11.Questionnairesfrom54participantswerescoredforninemeasures, includingthefirst:orderfactors(attentionalimpulsiveness,motorimpulsiveness, andnonplanningimpulsiveness)andsecond:orderfactors(attention,motor,self: control,cognitivecomplexity,perseverance,cognitiveinstability)ofimpulsiveness. Themeanscoreofeachsubsetwasdeterminedforthreegroups:allparticipants (n=54),substanceusingmothersonly(n=22),andnon:substanceusingmothers only(n=32).thedataforeachofthesethreegroupswerefurthertestedfor normalityusingthekolmogorov:smirnovtest. PSI*SF.Questionnairesfrom45participantswerescoredforthreemeasures, includingparentaldistress,parent:childdysfunctionalinteraction,anddifficultchild, byaddingtherespectiveresponsesforeachsubset.ninemotherswereexcludedfor incompletedata.themeanscoreofeachsubsetwasdeterminedforthreegroups: allparticipants(n=45),substanceusingmothersonly(n=21),andnon:substance usingmothersonly(n=24).thedataforeachofthesethreegroupswerefurther testedfornormalityusingthekolmogorov:smirnovtest.

32 26 Statistical"Analysis.Foreachself:reportmeasure,themeanscoresofeachsubset wereexaminedfordifferencesbetweensubstanceusingandnon:substanceusing mothers.forgroupsinwhichthedataforsubstanceusingandnon:substanceusing motherswerebothnormallydistributed,at:testwasused.forgroupsinwhich eitheronegrouporbothwerenotnormallydistributed,themann:whitneytestwas used.statisticalsignificancefordifferencesbetweengroupswasdeterminedusinga Bonferroni:correctedalphaformultiplecomparisons.FortheBIS/BAS,significance wasdeterminedbyanalphaof.05/5or.01.forthebis:11,significancewas determinedbyanalphaof.05/9or.0056.forthepsi:sf,significancewas determinedbyanalphaof.05/3or.012. GiventheapparentmodulationoftheN170latencybysubstanceuse(see Results),correlationsbetweentheERPcomponentsofvisualstimuliandself:report measureswereexamined.correlationsbetweenerpcomponentsbetweenauditory stimuliandself:reportmeasureswerenotexamined,asthereappearedtobeno significantmodulationoftheauditoryerpcomponent(n100)bysubstanceuse. Specifically,therewerenosignificanteffectsofsubstanceusestatusonN100 amplitude[f(1,52)=1.10,p=.298;η 2 partial=.02]andn100latency[f<1;η 2 partial=.01]. ThedegreeofcorrelationwasdeterminedbetweeneachofthevisualERP components(n170latency,n170amplitude,p1latency,p1amplitude)andthe meanscoresofeachsubsetofbis/basscale,bis:11,andpsi:sfself:report measuresforallmothers,substanceusingmothersonly,andnon:substanceusing mothersonly.allerpcomponentswerenormallydistributed.apearsoncorrelation

33 27 coefficient(pearson sr)wasdeterminedifthedatafromthesubsetwerenormally distributed.aspearman srhowasdeterminedifthedatafromthesubsetwerenot normallydistributed.statisticalsignificanceofeachcorrelationcoefficientwas determinedusingabonferroni:correctedalphaformultiplecomparisons.forthe BIS/BAS,significancewasdeterminedbyanalphaof.05/20or.0025.FortheBIS: 11,significancewasdeterminedbyanalphaof.05/36or.0014.ForthePSI:SF, significancewasdeterminedbyanalphaof.05/12or Results Catch"Trial"Response" Ofthewomenincludedinthefinalanalyses,overallaccuracywas91%for auditorystimuliand95%forvisualstimuli(n=48;fourparticipantsdidnothave accuracydataduetotechnicalissueswithe:primeresponserecording). ERP"Data"for"Infant"Faces" P1Amplitude.TheP1amplitudewasnotmodulatedbyemotionalexpression[F<1; η 2 partial<.01],hemisphere[f<1;η 2 partial=.01],orsubstanceusestatus[f(1,52)=1.32, p=.255;η 2 partial=.03].therewasamarginal,non:significantinteractionbetween emotionalexpressionandsubstanceusestatus[f(2,104)=2.73,p=.070;η 2 partial =.05],andtherewerenoothersignificantinteractions[F s<1;η 2 partial.01].there

34 28 werenoeffectsofemotion,hemisphere,ortheirinteractionsinsubstanceusingor non:substanceusingmothersseparately. P1Latency.TheP1latencywasnotmodulatedbyemotionalexpression[F<1;η 2 partial <.01],hemisphere[F(1,52)=1.30,p=.259;η 2 partial=.02],orsubstanceusestatus [F(1,52)=1.19,p=.28;η 2 partial=.02].therewerenoothersignificantinteractions betweenthesevariables[f s<1.77;p s>.175;η 2 partial<.03]. Thus,thesefindingssuggestthattheP1asamarkerofearlyperceptual processingofvisualstimuliwasunaffectedbyinfantemotionalexpressionand substanceusestatusofthemothersinthissample. N170Amplitude.TheN170amplitudewasnotmodulatedbyemotionalexpression [F<1;η 2 partial=.01],hemisphere[f<1;η 2 partial=.02],substanceusestatus[f(1,52)= 1.60,p=.211;η 2 partial=.03].therewerenoothersignificantinteractionsbetween thesevariables[allf s<1.48;p s>.234;η 2 partial<.03]. N170Latency.TherewasasignificantmodulationoftheN170latencybysubstance usestatus[f(1,52)=6.08,p=.017;η 2 partial=.11].comparedtonon:substanceusing mothers,then170latencyinsubstanceusingmotherswaslater(meann170 latency=168.05±17.96msversus158.00±12.01ms,p=.017).then170latency wasunaffectedbyemotion[f(2,104)=1.81,p=.168;η 2 partial=.03]andhemisphere [F(1,52)=1.62,p=.208;η 2 partial=.03].therewerenoothersignificantinteractions betweenthesevariables[allf s<1;η 2 partial<.01].

35 29 Thus,thesefindingssuggestthattheN170asamarkerofearlystructural encodingoninfantfacesismodulatedbymaternalsubstanceuse. Self*Report"Measures"and"Correlations"with"ERP"Data" BIS/BASscale.AspresentedinTable3,substanceusingmothershadhighermean scoresinthebassubscalesandalowermeanscoreinthebisscalecomparedto non:substanceusingmothers,althoughthesedifferenceswerenotstatistically significant.substanceusingmothersscoredslightlyhigherthannon:usingmothers onthebasfun:seekingelement,thoughthisdifferencewasalsonotstatistically significant(meanscore=11.83±2.17versus11.13±2.20,mann:whitneyu=253, n1=31,n2=22,p=.11). AscanbeseeninFigure2,therewasasmallcorrelationbetweentheN170 latencyandbasfun:seekingscoreinallmothers(pearson sr=.274,p<.05).no correlationwasobservedinsubstanceusingmothersalone(spearman srho=.093, p=.68)andamediumcorrelationwasobservedinnon:substanceusingmothers alone(pearson sr=.355,p=.05).inaddition,therewasasmallcorrelationbetween thep1latencyandthebasfun:seekingscoreinallmothers(pearson sr=.256, p=.07).table4summarizestheresultsbetweenallerpcomponentsandthe BIS/BASsubscalesinallmothers. Takentogether,thesefindingssuggestthatsubstanceusingmothershave higherbassensitivityandlowerbissensitivity,thoughthesefindingswerenot

36 30 statisticallysignificant,andthatacrosstheentiresampleofwomen,alargern170 latencyisassociatedwithahigherbasfun:seekingscore. BIS:11.Substanceusingmothershadhighermeanscoresinallninemeasuresof impulsivitycomparedtonon:substanceusingmothers,asshownintable5. Substanceusingmothersscoredsignificantlyhigherthannon:usingmothersinthe motorimpulsivenessfactorofimpulsivity. AsshowninFigure3,therewasasmallcorrelationbetweenthecognitive complexityfactorandn170latency(pearson sr=.260,p=.06),wherelaterlatency isassociatedwithhighercognitivecomplexityscores.thiscorrelationwasnot observedinsubstanceusingmothersalone(spearman srho=.175,p=.44)ornon: usingmothersalone(spearman srho=.080,p=.66).therewasnocorrelation betweenthecognitivecomplexityfactorandp1latency(pearson sr=.049,p=.73). Table6summarizestheresultsbetweenallERPcomponentsandtheBIS:11 subscalesinallmothers. Thus,thesefindingssuggestthatsubstanceusingmothersscorehigheron measuresofimpulsivityandthatacrosstheentiresampleofwomen,alargern170 latencyisassociatedwithahigherlevelofimpulsivityrelatedtocognitive complexity. PSI:SF.Nosignificantdifferenceswerefoundinmeasuresofparentingstress betweensubstanceusingmothersrelativetonon:usingmothers,asshownintable 7.Substanceusingmothershadhighermeanscores,thoughstatisticallynon:

37 31 significant,inparentaldistresscomparedtonon:substanceusingmothers(mean score=25.57±9.87versus23.37±7.11,t(52)=:0.864,p=.39). AsshowninFigure4,therewasasmallcorrelationbetweenparental distressandn170latency(pearson sr=.253,p=.09),wherelaterlatencyis associatedwithhigherparentaldistressscores.therewasamediumcorrelation betweenparentaldistressandn170latencyinsubstanceusingmothersalone (Pearson sr=.324,p=.15),thoughnocorrelationexistedinnon:usingmothers alone(pearson sr=.045,p=.84).therewasasmallercorrelationbetweenparental distressandp1latency(pearson sr=.148,p=.33).table8summarizestheresults betweenerpcomponentsandpsi:sfsubscalesinallmothers. Thus,thesefindingssuggestthatsubstanceusingmothershaveahigherlevel ofparentaldistress,thoughthisfindingwasnotstatisticallysignificant,andthat acrosstheentiresampleofwomen,alargern170latencyisassociatedwithahigher levelofparentaldistress. Discussion Inthepresentstudy,self:reportmeasuresofmotivation,impulsivity,and stresswereanalyzedtoidentifypotentialpredictorsofadifferentialneural responsetovisualinfantcuesinsubstanceusingandnon:usingmothers.inthe initialstudy,itwasfoundthattheface:specificn170erpcomponentpeakedlaterin substanceusingmotherswhencomparedtonon:usingmothers.thismodulationof

38 32 then170bysubstanceusewasnotseeninthep1,anearlymarkerofvisual processing,suggestingthatthefindingdidnotreflectageneralizedslowingof perceptualprocessesrelatedtosubstanceuse.inthecurrentstudy,wefoundthat thelaterlatencyofthen170peakwaspredictedbyhighersensitivitytofun:seeking behavioralmotivation,higherlevelsofthecognitivecomplexityfactorofimpulsivity, andhigherlevelsofparentaldistress.theseresultsprovidefurtherinsightintothe behavioralmanifestationsofdifferentialearlyperceptualprocessingofinfantfaces. Behavioral"Motivation"Systems"" Wefoundthatsubstanceusingmothersrelativetonon:usingmothershada highersensitivitytoallbascomponentsandalowersensitivitytobis,althoughthe differenceswerenotstatisticallysignificantwhencontrolledformultiple comparisons.inastudyutilizingthebis/basscalesincollegestudents,drug addictedindividualswerefoundtohavesignificantlyhigherbasfun:seeking,drive, andtotalscoreswhencomparedtohealthycontrols(78).thus,theabsenceof significantdifferencesinbis/bassensitivitybetweenthegroupsofthepresent studymaybearesultofamoremoderateseverityofdruguseamongthesampleof mothersrelativetothedrugaddictedsample.theseverityofdrugusewasnot measuredinthissampleofmothers,animportantlimitationtothisstudy(discussed below).inaddition,theabsenceofsignificancedifferencesmayalsoberelatedto thesamplesize.

39 33 WefoundasmallcorrelationbetweenN170latencyandBASfun:seeking scoreinallmothers,thoughthisdidnotreachstatisticalsignificanceafter controllingformultiplecomparisons.specifically,alatern170latencywas associatedwithahigherbasfun:seekingscore.thiscorrelationappearedtobe drivenprimarilybythenon:substanceusinggroup.thiseffectmaynothaveshown upinthesubstanceusinggroupduetoitssmallsamplesize.importantly,ahigher BAS:funseekingscorewasalsoassociatedwithalaterP1latency.Thus,theeffect mayinfactrepresentageneralizedslowingofvisualprocessingandmore investigationwillbenecessarybeforetheseresultsaregeneralized. TheN170haspreviouslybeenshowntobemodulatedbythemotivational significanceofastimulus(79).inthisstudy,then170amplitudewassmallerin responsetofacesassociatedwithmonetaryrewardrelativetounrewardedfaces, suggestingapreferentialprocessingandamoreefficientstructuralencoding processforfacesassociatedwithreward.incontrasttothepresentstudy,the resultsshowednoeffectofmotivationonn170latency.thecorrelationbetween then170andbasfun:seekingfoundinthepresentstudymayinfactrepresent delayedengagementtothestimulusasinfluencedbyitsrewardsalience.thefun: seekingcomponentmeasuresawillingnesstospontaneouslyapproachanovel event(80).thistypeofbehaviorisexpectedindrug:seekingindividuals,astheyare stronglymotivatedtoacquiresubstancesandarewillingtoapproachnovel situationsinordertoachievethisgoal.ithasbeenproposedthatthefun:seeking componentofthebasisrelatedtobothrewardreactivityandimpulsivity(81)both ofwhichappeartobealteredinaddictiveprocesses(5,82).thisalterationinthe

40 34 behavioralactivationsystemwithsubstancesservingastheprimarymotivation maythenleadtodelayedengagementofrewardingnon:substancestimuli,suchas infantcues,whichwasmanifestedasadelayedlatencyofthen170peakinresponse toinfantfacesinthepresentstudy. Impulsivity" Substanceusingmothersscoredsignificantlyhigheronthesecond:order impulsivityfactorofmotorimpulsiveness.theyalsoscoredhigheronallother measuresofimpulsivity,includingthecognitivecomplexityfactor,thoughthese resultsdidnotreachstatisticalsignificanceaftercontrollingformultiple comparisons.theseresultsareconsistentwithpreviousfindings,assubstanceuse hasbeenassociatedwithhigherlevelsofimpulsivityonbothself:reportand neurocognitivemeasures(82).althoughimpulsivityhasbeenexaminedextensively inrelationtopsychostimulants,ithasalsobeenlinkedtoopiates,alcohol,mdma, andnicotineuse. Wefoundasmallcorrelationbetweencognitivecomplexityfactorof impulsivityandn170latencyacrosstheentiresampleofwomen,thoughthisdid notreachstatisticalsignificanceaftercontrollingformultiplecomparisons. Specifically,alaterN170latencywasassociatedwithahigherscoreofthecognitive complexityfactorofimpulsivity.pattonandcolleagues(66)describethecognitive complexityfactorasthedegreetowhichanindividual enjoy[s]challengingmental tasks,withahigherscoredenotinglesspleasurederivedfromthesementaltasks.

41 35 Giventhisdeficitincognitivecomplexity,animpulsivemothermaynotfindthe samerewardsalienceinherinfant scues,orbeabletocomputetherewardvalue relatedtoherinfant.forinstance,excessivecryingandcolicarecommonlyreported behaviorsinearlyinfancytowhichamothermustrespond(83).cryingsyndromes canrepresentaresponsetoadistinctorganiccausein<5%ofcasesornormal cryingbehavior(84),andconsolingacryinginfantrequirescomplexthinkingbythe motherinordertodeterminethesourceoftheinfant sdistress.difficultinfant temperamentisassociatedwithmaternalanxiety(85),andcomplexthought processisnecessaryforthemothertorealizethatrespondingtothecryis associatedwithadelayedreward.thus,ifamotherdidnotenjoycomplexthinking, shewouldnotfindcaringforherinfantasrewarding.inthepresentstudy,this decreasedrewardsaliencetoinfantcuesmayhavebeenmanifestedasadifferential earlyperceptualprocessingofinfantfaces.furthermore,thecognitivecomplexity factorofimpulsivityisexpectedinaddictivebehaviors,asindividualsmaybeless likelytothinkaboutthefutureconsequencesoftheiractions,actingwiththedrugas theirprimarymotivationatthecostoftheirinfant swell:being. Stress" Surprisingly,nostatisticallysignificantdifferenceswerefoundinmeasures ofparentingstressinsubstanceusingmothersrelativetonon:usingmothers.itwas hypothesizedsubstanceusingmotherswouldperceiveinfantcuesasmorestressful, andtheywouldthereforescorehigheronthedifficultchildsubscalecomparedto

42 36 non:usingmothers.furthermore,itwashypothesizedthattheirinteractionswith theinfantwouldhavelessrewardsaliencerelativetonon:usingmothers,andthey wouldthereforescorehigherontheparent:childdysfunctionalinteractionsubscale. However,thesefindingswerenotobservedinourstudy.Itwasfoundthat substanceusingmothersscoredhigherontheparentaldistresssubscale,though thisfindingwasnotstatisticallysignificant. Animportantlimitationtothestudyofself:reportmeasuresofparenting stressisresponsebias,orreportinganswersthattheparticipantpresumestobe moresociallydesirable(86).inonestudy,reportingeverydayhassleswas negativelyassociatedwithsocialdesirability;theauthorsofthisstudysuggestthis isbecausereportingeverydayhasslesindicatesaninabilitytohandledailylife, whichmaybefrowneduponbyothers(87).similarly,mothersinthepresentstudy maybelesslikelytoreportthestressassociatedwithparentingasitmaynotbe viewedfavorably,whichmayhaveaffectedourabilitytopickupsignificant differencesbetweenthesubstanceusingandnon:usinggroups.anotherimportant limitationtotheanalysisofthepsi:sfself:reportmeasureswasthesmallersample size(n=45).ninewomenwereexcludedduetoincompletedata,whichmayhave affectedtheabilityoftheanalysistopickupsignificantdifferencesbetweengroups, andperhapsadditionalsignificantcorrelationsbetweenmeasuresofparentalstress andthen170. WefoundasmallcorrelationbetweenparentaldistressandN170latency, thoughthisdidnotreachstatisticalsignificanceaftercontrollingformultiple

43 37 comparisons.specifically,alatern170latencywasassociatedwithahigher parentaldistressscore.thiseffectappearedtobedrivenprimarilybythesubstance usinggroup.theparentaldistressscoreindicatesdistressassociatedwithpersonal factorssuchasconflictwithaspousethatresultfromthelimitedabilitytheparent hastofulfillotherrolesduetothedemandsofraisingachild(69).thiscorrelation mayrepresentaconsequenceoftheinteractionbetweenalteredrewardandstress pathwaysinaddictiveprocesses.oxytocinmayplayaroleindownregulatingstress inhumanmothers,assuggestedbyarecentstudyinwhichinteractionswithinfants activatedrewardpathwaysandincreasedperipheraloxytocin(8),whichisthought tomediateahyporesponsivereactiontostressintheperipartumperiod(29). Withinthiscontext,thecorrelationbetweentheN170latencyandparentaldistress mayinfactrepresentheightenedstressreactivityasaresultoftheattenuationof therewardingvalueofinfantcuesinsubstanceusingmothers. Limitations"and"Considerations" Theresultsofthisstudymustbeconsideredinlightofitslimitations.The discussionhighlightstrendsnotedamongthesample,whichwewouldbecautious aboutgeneralizingwithoutfurtherinvestigation.importantly,theabsenceof statisticallysignificantcorrelationsbetweenerpcomponentsandtheself:report measuresdoesnotdiscounttheimportanceofthesetrends.onelimitationthatmay accountforthisincludesthesmallsamplesize,whichmayhaveaffectedthepower ofthestudytopickupsignificantdifferences.

44 38 Thepresentstudywasbasedundertheframeworkthatsubstanceuseasa wholerepresentsanaddictiveprocess,motivatedbytherewardofdruguseand reliefofnegativeaffectassociatedwithwithdrawal.however,oneimportant limitationofthisstudyisthatadifferentiationbetweenseveritiesofsubstanceuse amongwomeninthissamplewasnotmade.themagnitudeoftheeffectof substancesontherewardandstresspathwayslikelydependsontheseverityof substanceuse,withagreaterdegreeofdysregulationoccurringinindividualswho aredependentonthesedrugs.dsm:ivcriteriaofsubstancedependenceinclude toleranceandwithdrawal,twoextrememanifestationsofthedysregulationofthe stressandrewardneuralcircuitry,whicharenotnecessarilyseeninsubstance abuseorsubstanceuse(88).itispossiblethatthewomeninthissamplerepresent substanceusersofmoderateseverity,inwhomthedegreeofdysregulationwasnot substantialenoughtoallowforsignificantdifferencesinbehavioralmeasuresor theircorrelationswiththeerpcomponents.arelatedlimitationisthatthe substancesusedbythewomeninthesamplewerevaried,andfurtherinvestigation inmorehomogenoussamplesiswarrantedbeforetheseresultsaregeneralized. Asmentionedpreviously,animportantlimitationofself:reportmeasuresof attitudesandbehaviorsinempiricalresearchistheresponsebias(86).inthe presentstudy,theparticipantmayhaveviewedunregulatedmotivation,higher impulsivity,andenhancedstressreactivityassociallyundesirableandthus reportedtheseresponsesless,whichmayhavelimitedourabilitytopickup significantdifferencesbetweensubstanceusingandnon:usinggroups.future investigationcouldsupplementthepresentstudybylookingatlaboratorymeasures

45 39 ofimpulsivity,suchthestrooptestanddelaydiscountingtasks(82).inaddition, investigationinvolvingphysiologicalmarkersofstress,suchaschangesincortisol levels(89)orheartrate(90),couldservetovalidateourself:reportmeasuresof stress.additionally,substanceusingmothersdifferedsignificantlyfromnon:using motherswithrespecttotheiryearsofeducation.differencesinliteracyorperhaps evenimpairedcognitionduetosubstanceusemayhaveinfluencedtheirabilityto completetheself:reportmeasuresproperly,whichmayalsohaveinfluencedour results.thishighlightstheimportanceofutilizingmoreobjectivetechniques,such astheeeg,ininvestigatingdifferencesbetweensubstanceusingmothersandnon: usingmothers. Finally,futureresearchshouldinvestigatelater,morecognitivecomponents oftheerpwaveforminsubstanceusingandnon:usingmothers.thepresentstudy focusedonearlyperceptualcomponentsoftheerp,lookingatrapidresponsesto infantcues.thisnotionisconsistentwiththetheoryofintuitiveparentingproposed bypapousekandpapousek(91),orthenotionthatparentingcanincludebehaviors ofwhichtheparentisnotconsciouslyaware.anerpcomponentthatmaybeof interestisthelatepositivepotential(lpp),whichhasbeenimplicatedasamarker ofemotionalprocessing(92).interestingly,ithasbeenimplicatedinthereappraisal ofemotionallyevocativestimuliinresponsetointernalandexternalfactors(93). Substanceusemayserveasanexternalfactorthataltersamother sperceived salienceofemotionallyevocativeinfantstimuli,whichmayinturnimpairherability torespondtothesecues.thedesignofthepresentstudycanbeappliedtofuture investigationinvolvingthelpp.

46 40 Conclusion" Insummary,thepresentstudyinvestigatedpredictorsofadifferentialneural responsetovisualinfantcuesinsubstanceusingandnon:usingmothers.wefound thatsubstanceusingmothersscoredhigheronbasfun:seekingsensitivity,the cognitivecomplexityfactorofimpulsivity,andparentaldistress.furthermore,we foundthatacrosstheentiresampleofmothers,thelaterlatencyofthen170was predictedbyahighersensitivitytothefun:seekingcomponentofthebasand higherlevelsofboththecognitivecomplexityfactorofimpulsivityandparental distress.weinterpretthesefindingstosuggestthatearlyvisualprocessingofinfant facesmaybecompromisedinmotherswithhighersensitivitytothefun:seeking componentofthebas,higherlevelsofimpulsivityrelatedtocognitivecomplexity, andhigherlevelsofparentaldistress,asallleadtoreducedsalienceofrewarding infantcues.becausethesetraitsweremorelikelytobefoundinsubstanceusing mothers,theseresultslendfurthersupporttothehypothesisthatdysregulationof therewardandstresspathwaysoccurinaddictiveprocesses,whichmayinturn affectparentingbyalteringsensitivitytoinfantcues.

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54 48 Figure1.Electrodelayoutforgeodesicsensornet(ElectricalGeodesics Incorporated)(61).P1andN170ERPsweredeterminedbyaveraginglatencyat6 electrodesoverleft(58,59,64,65,69,70)andright(90,91,92,95,96,97)scalp sites. Table1.Substancesusedbymothers(n=31;1participantinrehabilitation treatment) Substance Percentagereporting use Tobacco 71% Marijuana 19% Heroin 3% Amphetamines 3% Methadone 3% Alcohol 6% Cocaine 6% Opiates 3% Othersubstancenotdisclosed 19%