Depression and Anxious Apprehension Distinguish Frontocingulate Cortical Activity During Top ...

14 Pages·2011·0.67 MB·English

JournalofAbnormalPsychology ©2011AmericanPsychologicalAssociation
2011,Vol.120,No.2,272–285 0021-843X/11/$12.00 DOI:10.1037/a0023204
Depression and Anxious Apprehension Distinguish Frontocingulate Cortical
Activity During Top-Down Attentional Control
Rebecca Levin Silton, Wendy Heller, Marie T. Banich
Anna S. Engels, David N. Towers, UniversityofColoradoatBoulder
Jeffrey M. Spielberg, J. Christopher Edgar,
Sarah M. Sass, Jennifer L. Stewart, and
Bradley P. Sutton
UniversityofIllinoisatUrbana-Champaign
Gregory A. Miller
UniversityofIllinoisatUrbana-Champaign
Anetworkconsistingofleftdorsolateralprefrontalcortex(LDLPFC)anddorsalanteriorcingulatecortex
(dACC)hasbeenimplicatedintop-downattentionalcontrol.Fewstudieshavesystematicallyinvesti-
gatedhowthisnetworkisalteredinpsychopathology,despiteevidencethatdepressionandanxietyare
associated with attentional control impairments. Functional MRI and dense-array event-related brain
potential (ERP) data were collected in separate sessions from 100 participants during a color–word
Stroop task. Functional MRI results guided ERP source modeling to characterize the time course of
activityinLDLPFC(300–440ms)anddACC(520–680ms).Atlowlevelsofdepression,LDLPFC
activity was indirectly related to Stroop interference and only via dACC activity. In contrast, at high
levelsofdepression,dACCdidnotplayaninterveningrole,andincreasedLDLPFCactivitywasdirectly
relatedtodecreasedStroopinterference.Specifictohighlevelsofanxiousapprehension,higherdACC
activitywasrelatedtomoreStroopinterference.Resultsindicatethatdepressionandanxiousapprehen-
sionmodulatetemporallyandfunctionallydistinctaspectsofthefrontocingulatenetworkinvolvedin
top-downattentioncontrol.
Keywords:depression,anxiousapprehension,dACC,LDLPFC,attention
Attentionaldifficultiesarehighlightedaskeydiagnosticcriteria information is interpreted in a negative manner (Gotlib & Kras-
for both depression and anxiety in the Diagnostic and Statistical noperova, 1998; Gotlib, Krasnoperova, Yue, & Joorman, 2004).
Manual of Mental Disorders (4th ed., text rev.; DSM–IV–TR; These attentional abnormalities may intensify and prolong symp-
American Psychiatric Association, 2000). Contributing to cogni- tomsofsadnessandworryduetothenegativelybiasedmisinter-
tivemisattributions,individualswithdepressionoftendemonstrate pretationofeventsandinformationthatiscommonlyobservedin
an attentional bias that favors negative information, and neutral depressionandanxiety(Gotlibetal.,2004),leadingtoadownward
Rebecca Levin Silton, Anna S. Engels, David N. Towers, Jeffrey M. Institute on Drug Abuse Grant R21 DA14111); and the University of
Spielberg,SarahM.Sass,andJenniferL.Stewart,DepartmentofPsychol- Illinois Beckman Institute, Department of Psychology, and Intercampus
ogy,UniversityofIllinoisatUrbana-Champaign;WendyHeller,J.Chris- ResearchInitiativeinBiotechnology.Thisarticleisbasedondatathatwere
topher Edgar, and Bradley P. Sutton, Department of Psychology and includedinRebeccaLevinSilton’sdoctoraldissertation.Aportionofthis
Beckman Institute Biomedical Imaging Center, University of Illinois at researchwaspresentedatthe2009meetingoftheSocietyforResearch
Urbana-Champaign;MarieT.Banich,DepartmentofPsychology,Univer- inPsychopathology.Adifferentarticlethatinvolvesasubsetofthepartic-
sity of Colorado; Gregory A. Miller, Departments of Psychology and ipants included in this article was published in NeuroImage. That article
PsychiatryandBeckmanInstituteBiomedicalImagingCenter,University evaluatedthetemporalcourseofthedorsalanteriorcingulatecortexandthe
ofIllinoisatUrbana-Champaign. left dorsolateral prefrontal cortex proposed in the cascade-of-control model
Rebecca Levin Silton is now at Department of Psychology, Loyola and did not address the role of psychopathology. We thank Adrienne
UniversityChicago;AnnaS.EngelsisnowatDepartmentofPsychology Abramowitz,KirstinAschbacher,PatrickBerg,KeithBredemeier,Amanda
andSocial,Life,andEngineeringSciencesImagingCenter,Pennsylvania Bull,EmilyCahill,LauraCrocker,MonicaFabiani,KaraFedermeier,Joscelyn
StateUniversity;J.ChristopherEdgarisnowatDepartmentofRadiology, Fisher,ChristianHendershot,BrendaHernandez,KarstenHoechstetter,An-
Children’sHospitalofPhiladelphia;SarahM.SassisnowatDepartment gelaLawson,ReneeThompson,EdelynVerona,andStacieWarrenfortheir
ofPsychology,UniversityofTexasatTyler;JenniferL.Stewartisnowat contributionstothisproject.
PsychiatryDepartment,UniversityofCalifornia,SanDiego. CorrespondenceconcerningthisarticleshouldbeaddressedtoRebecca
This research was supported by National Institute of Mental Health LevinSilton,DepartmentofPsychology,LoyolaUniversityChicago,1032
Grants P50 MH079485, R01 MH61358, and T32 MH19554; National WestSheridanRoad,Chicago,IL60660.E-mail:[email protected]
272
DEPRESSION,APPREHENSION,ANDCORTICALACTIVITY 273
spiral of maladaptive thoughts. Individuals with anxiety demon- anxietydisordertoprecedeandco-occurwithdepression(Kessler
strate an attentional bias to threat-related information (Compton, etal.,1996;Kessler,Zhao,Blazer,&Swartz,1997),
Heller, Banich, Palmieri, & Miller, 2000; Nitschke & Heller, Banich(2009)identifiedanetworkofbrainregionsinvolvedin
2002). Once threatening stimuli are attended to, it is difficult for top-downattentionalcontrol,includingleftdorsolateralprefrontal
individuals with anxiety to disengage their attention and shift to cortex (LDLPFC) and dorsal anterior cingulate cortex (dACC).
less anxiety-provoking thoughts. These attentional control diffi- Present analyses addressed the possibility that depression and
culties often affect daily life function. In clinical settings, it is anxious apprehension differentially influence this network. Ac-
typicaltohearclientswithdepressionand/oranxietycomplainof cording to Banich’s (2009) cascade-of-control model, during
“difficulties attending to a conversation or lecture” or “problems attentionally demanding tasks LDLPFC imposes a top-down at-
focusing on reading or homework.” Attentional control problems tentional set for task-relevant processing while late-stage or
and related executive function deficits can greatly interfere with response-related aspects of selection are implemented by dACC.
interpersonal relationships and daily life activities such as job Hence, a temporal course in which LDLPFC is activated first,
performance (Jaeger, Berns, Uzelac, & Davis-Conway, 2006). In followed by dACC, is a key component of Banich’s cascade-of-
turn,thesedifficultiesfuelcyclesofself-deprecation,sadness,and control model. Furthermore, the model posits that the less top-
worry. Cognitive and neural mechanisms associated with the at- down control exerted by LDLPFC, the more activity should be
tentional problems that accompany symptoms of depression and observedindACC,asitwillneedtoresolveanyremainingaspects
anxietyarenotwellunderstood. ofselectionbeforearesponsecanbeemitted.
Complicatingthecharacterizationofthesephenomena,depres- Arecentsourceanalysisstudyinvestigatingthetimecourseof
sionandanxietyfrequentlyco-occur(Engelsetal.,2010;Kessler, activityinLDLPFCanddACCduringanattentionalcontroltask
DuPont, Berglund, & Wittchen, 1999). On the basis of DSM– (color–wordStroop)inanonclinical,undergraduatesample(Silton
IV–TR criteria, it can often be difficult, or even impossible, to et al., 2010) provided support for this model.1 Results indicated
distinguish whether an individual’s attentional problems are re- that LDLPFC activity preceded dACC activity. Moreover, mea-
lated to depression, anxiety, or both. Further developing clinical suresofperformance(Stroopinterference)weredirectlyrelatedto
assessmentmethodsthathavehighdiagnosticsensitivityandspec- later dACC activity but not LDLPFC activity. The Stroop inter-
ificity is crucial to advancing treatment for these debilitating ferenceeffectreferstoatypicalresponsepatterninvolvinglonger
disorders.Ifdifferentialpatternsofattentionalcontroldifficulties reactiontime(RT)followingincongruentstimuli(thewordredin
can be identified in depression and anxiety, it will inform blue ink) than congruent (the word red in red ink) or neutral
evidence-basedtreatmentsfordepressionandanxietythatinvolve stimuli(anonwordoranoncolorword,suchasXXXXorbond,in
training individuals to use attentional control methods, such as redink).TheextenttowhichdACCactivationinfluencedStroop
cognitive control therapy (Siegle, Ghinassi, & Thase, 2007) and performancedependedonthedegreeofearlierLDLPFCactivity,
mindfulness-basedcognitivebehavioraltherapy(Segal,Williams, showinganinterdependentrelationshipamongthesebrainregions.
&Teasdale,2002). Consistent with the cascade-of-control model, when LDLPFC
The effectiveness of attentional control or cognitive control activitywashigh,dACCactivitydidnotaffectperformance.This
trainingforindividualswithdepressionhasbeendemonstratedin pattern of activity was attributed to adequate top-down control
treatment outcome studies (Siegle et al., 2007) as well as in imposed by LDLPFC. When LDLPFC activity was low, high
experimentalresearch.Hertel(1994)showedthatindividualswith dACCactivitywasassociatedwithbetterperformanceandlonger
depressionwhowerecoachedtouseattentionalcontrolstrategies RT,suggestingthat,aspredicted,dACCwascompensatingforthe
achievedperformanceonanattentiontaskthatwascomparableto lack of top-down LDLPFC control. When LDLPFC and dACC
that of individuals without depression. These findings indicated activity were both low, a higher error rate and shorter RT were
that individuals with depression have sufficient attentional re- observed,indicatingalackofdACCcompensatoryaction.
sources;theirattentionalproblemsariseduetoafailuretocontrol Thesefindingsarerelevantforpsychopathology,astheStroop
these resources (Hertel, 1994). Fundamental attentional control (1935)taskhasbeenusedtoinvestigatecognitiveimpairmentsin
functions that are involved with maintaining focus on the task at depression in top-down control. A number of studies examining
hand, rather than getting distracted by threatening or negative performanceonthecolor–wordStrooptaskindepressedindivid-
task-irrelevant information, or getting caught up in a ruminative uals have shown a range of attentional difficulties evidenced by
loop,maybeinterruptedindepression(Hertel,2007)andanxiety increased RT, increased errors, and greater interference (Biringer
(Eysenck,Derakshan,Santos,&Calvo,2007). etal.,2005;Duncan&Owen,2000;Dunkinetal.,2000;Holmes
Several dimensions of psychopathology, including anhedonic & Pizzagalli, 2008; Paradiso, Lamberty, Garvey, & Robinson,
depression, anxious apprehension (worry), and anxious arousal 1997;Ravnkildeetal.,2002;Stordaletal.,2004;Videbechetal.,
(panicorautonomicarousal),areaccompaniedbyuniquepatterns 2004). Impaired Stroop performance has been reported for indi-
ofabnormalactivityinregionsofthebraininvolvedinattentional
control(e.g.,Engelsetal.,2007,2010;Nitschke,Heller,&Miller,
1Siltonetal.(2010)didnotaddresstherelationshipbetweenpsycho-
2000). In order to examine associated neural mechanisms of at-
pathology and the temporal course of LDLPFC and dACC. The present
tentionaldisruptionthataccompanydepressionandanxietysymp-
studywasdesignedtofollowupquestionsraisedaboutpsychopathologyin
toms,itisstrategictopartitionanxietyaccordingtothesetheoret-
theSiltonetal.study.Asafollow-upstudy,asupersetoftheSiltonetal.
ical and methodological distinctions. This is particularly relevant
sampleandsimilarmethodologywereusedinthepresentstudy.Results
becauseworryoranxiousapprehensionisakeyfeatureofgener- fromSiltonetal.guidedpresenthypothesesregardinghowdepressionand
alized anxiety disorder (GAD), and GAD is the most common anxietyinfluencethetemporalcourseofthefrontocingulatenetwork.
274 LEVINSILTONETAL.
viduals with major depressive disorder (Videbech et al., 2004), LDLPFCfunctionafterindividualswithdepressionreceivedcog-
recurrentmajordepressiveepisodes(Stordaletal.,2004),remitted nitive control therapy (Siegle et al., 2007). Decreased LDLPFC
depression(Biringeretal.,2005;Paradisoetal.,1997),andfailure activitywasobservedforaneasycognitivecontroltaskcondition,
to respond to antidepressant medication (Dunkin et al., 2000). andincreasedLDLPFCactivitywasobservedforamoredifficult
Recent research has revealed that abnormal focal LDLPFC and condition. These depressed individuals demonstrated improved
dACCactivityisrelatedtodepressionduringStroopperformance performance on this cognitive control task following treatment.
(Holmes&Pizzagalli,2008;Killgore,Gruber,&Yurgelun-Todd, These findings support other studies in pointing to changes in
2007; Wagner et al., 2006), but precisely how depression influ- patterns of DLPFC and ACC activation as a function of depres-
ences the timing and relations among relevant brain regions re- sion, although the precise nature and direction of these changes
mainsanopenquestion. remainstobedetermined.
Research investigating the relationship between anxiety and ThepresentstudyusedERPsourceanalysistoevaluatehowthe
color–word Stroop performance has used diverse definitions and frontocingulatenetworkdescribedinBanich’s(2009)cascade-of-
typesofanxiety,aswellasvariousparadigms,perhapscontribut- control model of top-down attentional control is affected by de-
ing to a lack of consistency in results. In an early study, a state pression and anxiety. Source analysis techniques are an ideal
manipulationofanxietyadverselyaffectedperformanceaccuracy method to study the timing of network function, as they provide
inanincongruentbutnotacongruentcondition(Hochman,1967). information regarding the time course of regional brain activity.
Fox (1993) compared behavioral performance for high- and low- Moderated mediation analyses were used to evaluate the hypoth-
trait-anxiousparticipantsonincongruent,neutral,andthreatening esisthatdepressionandanxietywouldinfluencethetimecourseof
words in a spatially “separated” Stroop task (attend to a central earlyLDLPFCactivityandlaterdACCactivityindifferentways
color patch and ignore the word in the periphery). High-trait- duringataskthatrequirestop-downattentionalcontrol(thecolor–
anxious participants showed interference effects for both incon- word Stroop task). It was predicted that depression would be
gruent and threat words presented in the periphery, suggesting a related to reduced earlier LDLPFC activity and that later dACC
generaldisruptionintheabilitytomaintainattentionalfocusthat activity would be related to either compensatory behavior, as
wasnotlimitedtothreateninginformation.Otherstudiesinvolving evidencedbyincreasedactivityandnormalStroopperformance,or
the color–word Stroop task have not found RT condition differ- alackofcompensatorybehavior,asindicatedbydecreasedactiv-
encesasafunctionofanxiety(Gehring,Himle,&Nisenson,2000; ity and poor Stroop performance. Anxious apprehension was hy-
Hajcak,McDonald,&Simons,2003). pothesizedtobeassociatedwithincreaseddACCactivityonly.It
The brain regions that were shown to work in conjunction to wasuncertainwhetherthispatternofnetworkactivitywouldaffect
exert attentional control in a nonclinical sample, specifically performance. Increased dACC activity was shown to mediate
LDLPFC and dACC (Silton et al., 2010), appear to be differen- Stroop performance only when LDLPFC activity was low and
tially affected in depression and anxiety. Depression has been associated top-down attentional control was poor (Silton et al.,
more commonly linked to reduced LDLPFC activity than has 2010). Because anxious apprehension was not expected to affect
anxiety(Fitzgeraldetal.,2006;Herringtonetal.,2010;Holmes& LDLPFC activity, it was uncertain whether potential changes to
Pizzagalli, 2008; Rogers, Bradshaw, Pantelis, & Phillips, 1998). subsequent downstream dACC activity (but not earlier LDLPFC
Both depression and anxiety have been associated with altered activity)wouldaffectperformance.
dACCactivity(Engelsetal.,2010;Hajcaketal.,2003).Anxiety
hastypicallybeenassociatedwithincreaseddACCactivity(Olvet
Method
& Hajcak, 2008; Paulus, Feinstein, Simmons, & Stein, 2004),
whereas both dACC hyperactivity and hypoactivity have been
reportedindepression(Georgeetal.,1997;Holmes&Pizzagalli, Participants and Selection Procedures
2008;Killgoreetal.,2007).Thesemixedfindingsmaybeinpart
duetounassessed,comorbidanxiety. Participants(N(cid:1)100)wererecruitedfromintroductorypsychol-
Limited research has focused on how psychopathology affects ogyclassesviagroupquestionnairescreeningsessionsaswellasfrom
frontocingulate networks. Mayberg’s (1997) proposed limbic- the community via advertisements placed in local newspapers and
corticalnetworkmodelofdepressionspecifies“ventral”and“dor- throughrecruitmenteffortsatthecampus-runcommunitypsychology
sal”components.Relevanttothepresentstudy,Maybergproposed clinic. Participants (45% female, 80% Caucasian) were paid volun-
thattheattentionalimpairmentsobservedindepressionarerelated teers ages 18–35 years (M (cid:1) 20.2, SD (cid:1) 3.6). Participants were
toabnormalitiesinthedorsalcomponents,whichincludeDLPFC, right-handedasdeterminedbytheEdinburghHandednessInventory
dACC, inferior parietal cortex, and striatum. In line with this (Oldfield,1971)andwerenativeEnglishspeakers.Becausepsycho-
model,HolmesandPizzagalli(2008)showedareductioninboth activemedicationsareknowntoaffectcognitivefunctionandrelated
LDLPFCanddACCactivityasmeasuredbyevent-relatedpoten- regional brain activity (Brody et al., 2001; Mayberg et al., 2000),
tial (ERP) source analysis during a color–word Stroop task at participantswerescreenedbyself-reporttobefreeofsuchmedica-
620-ms poststimulus presentation in individuals with depression tions.Participantswerealsoscreenedforabnormalcolorvision,loss
compared with controls. Reporting different findings using func- ofconsciousnessgreaterthan10min,claustrophobia,recentdrugor
tionalmagneticresonanceimaging(fMRI)methods,Wagneretal. alcoholuse,excessivecaffeineintake,andlackofsleep.Participants
(2006)observedthatindividualswithdepressionhadhyperactive weregivenalaboratorytour,wereinformedofthestudyprocedures,
LDLPFC but no changes in dACC activity relative to healthy and provided written consent. DSM–IV–TR diagnoses were used to
controls during Stroop performance. With implications for trans- selectparticipantsfromalargerprojectinordertoensurethatindi-
lationalresearch,anfMRIstudyshowedposttreatmentchangesin viduals who had a lifetime history of clinically defined depression
DEPRESSION,APPREHENSION,ANDCORTICALACTIVITY 275
wereincludedinpresentanalyses.Theparticipantselectionmethod regions involved in each (e.g., Engels et al., 2010). Although
describedherewasemployedpriortorunningsubsequentanalyses. participants completed other questionnaires as part of a larger
TheStructuredClinicalInterviewforAxisIDisorders,Non-Patient study, only the MASQ–AD-8 and PSWQ were analyzed in the
edition (SCID–NP, First, Spitzer, Gibbon, & Williams, 1997), was presentstudy.Withregardtoconstructvalidity,theMASQ–AD-8
administered to all participants to assess Axis I disorders. Lifetime predicts current major depressive episode and lifetime major de-
DSM–IV–TR diagnoses were determined by the interviewer and re- pressivedisorder(Bredemeieretal.,2010).Similarly,thePSWQ
viewedbyaconsensusteamconsistingofasecondintervieweranda is an excellent predictor of GAD (Behar, Alcaine, Zuellig, &
clinical faculty supervisor (Gregory A. Miller) reviewing a written Borkovec, 2003). See Table 1 for further information about de-
case summary detailing each criterion symptom on the scale: 1 (cid:1) mographics,andquestionnairescoresforthedepression,anxiety,
absent,2(cid:1)features(atleasttwosymptoms),3(cid:1)provisional(one andcomorbiddiagnosticcategoriesforthepresentsample.
shortoffullDSM–IV–TRcriteria),and4(cid:1)definite.SCID–NPdata Threeanalysesofvariancewereconductedtoexamine(a)whether
were used to select 34 participants who had a lifetime history of a participantswithdiagnoseddepressionscoredhigherthanthosewith-
provisionalordefinitedepressivedisorder,18ofwhomhadalifetime out diagnoses on the MASQ–AD-8, (b) whether participants with
history of one or more provisional or definite anxiety disorders. comorbid diagnoses scored higher than those without diagnoses on
ParticipantswithanxietydisordershaddiagnosesprimarilyofGAD both questionnaire measures, and (c) whether participants with co-
(n(cid:1)7),aswellasofobsessive-compulsivedisorder(n(cid:1)5),social morbid diagnoses scored higher than the participants with only de-
phobia(n(cid:1)5),specificphobia(n(cid:1)4),posttraumaticstressdisorder pression diagnoses on the PSWQ but not the MASQ–AD-8. The
(n(cid:1)4),panic(n(cid:1)1),andanxietynototherwisespecified(n(cid:1)1). participantswithcomorbidandpuredepressionwereexpectedtohave
TheSCID–NPdoesnotprovideinformationregardingcurrentanxiety comparable levels of depression as measured by the MASQ–AD-8
disorders,onlyinformationregardinglifetimehistoryofanxietydis- andtovaryonlyonanxietylevelsasmeasuredbythePSWQ.The
orders.Sixty-sixparticipantswerefreeofanydepressiveoranxiety resultswereasexpected.Theparticipantswithdepressiondiagnoses
disorders.Noneoftheparticipantswasinacurrentmajordepressive scoredhigherthanthosewithoutdiagnosesontheMASQ–AD-8,F(1,
episode.AlthoughparticipantswerescreenedforallAxisIdisorders, 80)(cid:1)5.41,p(cid:1).02.Theparticipantswithcomorbiddiagnosesscored
otherdisorderswerenotusedascriteriatoselectparticipantsforthe higherthanthosewithoutdiagnosesonthePSWQ,F(1,82)(cid:1)17.22,
presentstudy.Participants’diagnosticstatuswasnotrevealedtothe p(cid:2).00,andMASQ–AD-8,F(1,82)(cid:1)7.60,p(cid:1).01.Thepartici-
research team until after the participants had completed the entire
pants with comorbid diagnoses did not differ from those with only
study protocol. These participant selection methods were used to depressiondiagnosesontheMASQ–AD-8,F(1,32)(cid:1)0.12,p(cid:1).74,
ensurethatarangeofdepression-andanxiety-relatedpsychopathol-
buttheyscoredhigherthanthosewithonlydepressiondiagnoseson
ogywasrepresentedinthesample,asdimensionalanalysesofself- thePSWQ,F(1,32)(cid:1)9.33,p(cid:1).01.Giventhatthediagnosis-based
reporteddepressionandanxiousapprehensionwereusedtoexamine
categoricalgroupswereformedviaadifferentmeasure(theSCID–
theirmoderatingeffects(describedbelow).
NP) than the dimensional questionnaires, these analyses provided
Toprovidedimensionalmeasuresofdepression,anxiousappre-
evidenceforconvergentvalidity.
hension, and anxious arousal, participants completed the Mood
and Anxiety Symptom Questionnaire Anhedonic Depression
eight-item depressed mood subscale (MASQ–AD-8; Nitschke, Stimuli and Experimental Design
Heller, Imig, McDonald, & Miller, 2001; Watson, Clark, et al.,
1995; Watson, Weber, et al., 1995) and the Penn State Worry Inbriefoverview,ERPandfMRIdatawerecollectedfromall
Questionnaire (PSWQ; Meyer, Miller, Metzger, & Borkovec, participants during a task requiring top-down attentional control
1990; Molina & Borkovec, 1994). These measures have been (color–word Stroop task). The fMRI data were used to guide
showntoprovideeffectivediscriminationamongthesedimensions placement of ERP sources, and information regarding the time
(for review, see Nitschke et al., 2001) and to distinguish brain course of LDLPFC and dACC activity was extracted for neural
Table1
DemographicsandQuestionnaireScoresbyDiagnosticGroup
Comorbid Depression Nodiagnosis Fullsample
(n(cid:1)18) (n(cid:1)16) (n(cid:1)66) (N(cid:1)100)
Variable M SD M SD M SD M SD
Age 23.72 5.15 21.12 5.44 19 0.89 20.19 3.60
Gender(n)a 12/6 7/9 26/30 45/55
PSWQ 57.44 18.92 39.38 15.05 40.55 14.22 43.40 16.51
MASQ–AA 27.72 7.01 24.00 6.55 24.18 6.90 24.79 6.93
MASQ–AD-8 17.72 6.24 17.06 4.80 14.39 3.95 15.42 4.74
GAF 67.89 10.64 81.44 6.50 87.76 5.02 83.17 9.97
Note. PSWQ(cid:1)PennStateWorryQuestionnaire;MASQ–AA(cid:1)MoodandAnxietySymptomQuestionnaire–
AnxiousArousal;MASQ–AD-8(cid:1)MoodandAnxietySymptomQuestionnaire–AnhedonicDepressioneight-
itemdepressedmoodsubscale;GAF(cid:1)GlobalAssessmentofFunction.
aWomen/men.
276 LEVINSILTONETAL.
network analyses involving dimensional depression and anxious planarimagingsequence(repetitiontime(cid:1)2,000ms,echotime(cid:1)
apprehensionvariables. 25 ms, flip angle (cid:1) 80°, field of view (cid:1) 22 cm). Thirty-eight
Participants completed a color–word Stroop task and an obliqueaxialslices(slicethickness(cid:1)3mm,in-planeresolution(cid:1)
emotion–word Stroop task. Both tasks were administered during 3.4375(cid:6)3.4375mm,0.3-mmgapbetweenslices)wereacquired
anfMRIsessionandagainduringanelectroencephalogram(EEG) paralleltotheanteriorandposteriorcommissures.Aftertheecho-
session.TheorderofpresentationofthetwoStrooptaskswithina planar imaging sequence, a 160-slice MPRAGE structural se-
sessionwascounterbalancedacrossparticipants,aswastheorder quence was acquired (slice thickness (cid:1) 1 mm, in-plane resolu-
oftheEEGandfMRIsessions,withtheSCIDsessioninbetween tion(cid:1)1(cid:6)1mm)forregisteringeachparticipant’sfunctionaldata
for most participants. The emotion–word Stroop data do not ad- tostandardspace.
dress present goals and will not be considered further here. The Image processing and analyses relied primarily on tools from
color–wordStrooptaskconsistedofblocksofcolor-congruentor the FMRIB Software Library analysis package (http://www.fmri-
color-incongruentwordsalternatingwithblocksofneutralwords, b.ox.ac.uk/fsl). Each fMRI time series was first motion-corrected
with 256 trials in 16 blocks (four color congruent, four color with FMRIB’s Linear Image Registration Tool (Jenkinson, Ban-
incongruent,eightneutral).Halfthetrialsincongruentandincon- nister, Brady, & Smith, 2002), and spikes (artifactual sudden
gruent blocks were neutral, to prevent the development of word- intensity shifts) were corrected with the AFNI tool 3dDespike
readingstrategies.Therewereeightordersofstimuluspresentation (http://afni.nimh.nih.gov/afni).Participantsdemonstratedlessthan
for each Stroop task, designed specifically to control stimulus 3.3-mm absolute motion or 2-mm relative motion (participants
ordereffects.Eachparticipantreceivedoneoftheeightorders. withmotionexceedingthisthresholdwereexcludedfromanalysis,
Each trial consisted of one word presented in one of four ink beyond the 30 control participants relied on in the present analy-
colors(red,yellow,green,blue).Trialsbeganwiththepresentation sis). After motion correction and despiking, each time series was
ofawordfor1,500ms,followedbyafixationcrossfor275–725 correctedforgeometricdistortionscausedbymagneticfieldinho-
ms (onset-to-onset intertrial interval (cid:1) 2,000 (cid:3) 225 ms). Word mogeneity. Remaining preprocessing steps, single-subject statis-
presentation and response recording were controlled by STIM tics, and group statistics were implemented by FMRIB’s Expert
software(JamesLongCompany,CarogaLake,NY).InthefMRI Analysis Tool. The first three volumes of each data set were
session, words were presented in capital letters with Tahoma discardedtoallowthemagneticresonancesignaltoreachasteady
72-pointfontviabackprojectionontoascreenoutsidethescanner state.Eachtimeserieswasthentemporallyfilteredwithanonlin-
boreandamirrorfixedtotheheadcoil,providingaverticalspan ear high-pass filter (to remove drift in signal intensity), mean-
of2.9°andahorizontalspanof6.1°–16.4°.IntheERPsession,the basedintensity-normalizedbythesamesinglescalingfactor,and
same words were presented in Tahoma 72-point font on a CRT spatially smoothed via a third-dimensional Gaussian kernel (full-
monitor 1.35 m from the participants’ eyes, providing a vertical widthhalfmaximum(cid:1)5mm)priortoanalysis.
span of 1.5° and a horizontal span of 3.2°–8.7°. Participants Regressionanalyseswereperformedoneachparticipant’stime
responded with the middle and index fingers of both hands, with series with FMRIB’s Improved Linear Model. Statistical maps
eachtaskusingthesamemappingofcolortobutton.Therewasa were generated via multiple regression computed for each intra-
color-to-key-mapping acquisition phase of 32 practice trials. In cerebral voxel (Woolrich, Ripley, Brady, & Smith, 2001). An
additiontothe16wordblocks,therewerefourfixationblocks:one explanatory variable (EV) was created for each trial block type
at the beginning, one at the end, and two in the middle of the (colorcongruent,colorincongruent,neutral,rest),withthefixation
session.Inthefixationcondition,abrightenedfixationcrosswas conditiontheunmodeledbaseline.EachEVwasconvolvedwitha
presentedfor1,500ms. gammafunctiontobetterapproximatethetemporalcourseofthe
blood-oxygen-level-dependenthemodynamicresponse(e.g.,Agu-
irre, Zarahn, & D’Esposito, 1998; Miezin, Maccotta, Ollinger,
MRI Recording, Data Reduction, and Analysis
Petersen,&Buckner,2000).EachEVyieldedaper-voxeleffect-
FunctionalMRIdatawereanalyzedfromasubsetof30ofthe sizeparameterestimatemaprepresentingthemagnitudeofactivity
66participantswithoutapsychopathologyhistory,providingguid- associatedwiththatEV.Thebetavaluesfortheincongruentword
ance for the ERP source analysis that was carried out for all 100 condition were contrasted with those for the congruent word
participants.Two-tailedttestsshowedthatthe30participantswho condition,resultinginaper-voxelcontrastparameterestimatemap
were used in fMRI analyses did not differ from the other 36 for each subject. These functional activation maps as well as the
participants without anxiety or depression diagnoses in terms of corresponding structural MRI map were registered into Montreal
age,t(65)(cid:1)1.11,p(cid:1).27;genderbalance,(cid:4)2(1,N(cid:1)66)(cid:1)2.03, Neurological Institute stereotaxic space with FMRIB’s Nonlinear
p(cid:1).15;GlobalAssessmentofFunction,t(65)(cid:1)0.26,p(cid:1).80;or Image Registration Tool via FMRIB Software Library’s default
Stroop interference effect, t(65) (cid:1) (cid:5)0.78, p (cid:1) .44. Participants configurationfileandawarpresolutionof10mm.
withoutlifetimedepressionand/oranxietydiagnoseswereusedfor Inferential statistical analyses were carried out with FMRIB’s
fMRIanalysesbecausethepurposeofthestudywastounderstand Local Analysis of Mixed Effects. In order to identify regions
how network activity in depression and anxiety differs from typ- associated with the Stroop interference effect, significantly acti-
icalnetworkactivityobservedinhealthyindividuals. vatedvoxelswereidentifiedfortheincongruentminuscongruent
Themagneticresonancetechnologistandexperimenterassisted contrast via a one-sample t test, yielding a three-dimensional
the participant in correct placement of earplugs and protective functional z map image. Monte Carlo simulations via AFNI’s
headphones. Magnetic resonance data were collected using a AlphaSim program (Ward, 2000) estimated the overall signifi-
research-dedicated 3T Siemens Allegra. Three hundred and sev- cancelevel(probabilityofafalsedetection)forthresholding,using
enty functional images were acquired via a gradient-echo echo- agray-mattermasktolimitthenumberofvoxelsunderconsider-
DEPRESSION,APPREHENSION,ANDCORTICALACTIVITY 277
ation.Thesesimulationsprovidedazvalue(z(cid:1)3.0902,p(cid:1).01) stimulus onset were included in the individual participant aver-
andclustersize(34)combinationforthresholdingthatresultedin ages.Allparticipantsincludedinthesamplehadaminimumof16
anoverallfamilywiseerrorrateof.05.Clustersthatsurvivedthis trials for each condition average. Following these steps, the sur-
thresholding are reported in Table 2. Center of mass coordinates rogate multiple source eye correction algorithm was used to cor-
forclustersinhypothesizedregionsofinterestwereusedtoplace rectblinkartifactsforeachparticipant(Berg&Scherg,1994).In
regionalsourcesintheERPsourcemodel. themultiplesourceeyecorrectionmethod,usingallEEGchan-
nels, sources of brain and artifact activity (e.g., blink) are
Electrophysiological Recording, Data Reduction, and simultaneouslymodeled,andonlythemodeledblinkactivityis
Analysis removedfromeachEEGchannel.TheBergandScherg(1994)
method reduces distortion of brain activity by accounting for
Participantswereseatedinacomfortablechairinaquietroom
theEEGsignalduringtheestimationofeyeactivity(seeSilton
connectedtotheadjacentequipmentroombyintercom.EEGwas
et al., 2010, for additional details about the blink removal
recordedwithacustom-designedFalkMinow64-channelcapwith
process and application of the multiple source eye correction
equidistantly spaced Ag and AgCl electrodes. After placement
method).
of the electrode cap, electrode positions were digitized for
later topographic and source localization analyses. An additional SourcemodelingwascarriedoutwithBESA.Thesourcemodel
electrodewasplacedbeloweacheye;theseandnearbyelectrodes (see Figure 1B for full model) was created by placing a priori
inthecapprovidedabasisforofflineeye-blinkartifactcorrection regional sources based on center of mass coordinates for fMRI
of the EEG data implemented in BESA (Version 5.1.8; Berg & activation clusters obtained from the 30 psychopathology-free
Scherg,1994).Theleftmastoidservedastheonlinereferencefor participantsasdiscussedabove.Fourteencandidatelocationssur-
all other sites, including electrooculogram. Impedances were be-
vivedthresholding(seeTable2).Ifall14clusterswereplacedas
low 20 (cid:7), appropriate given the high input impedance of the
sources in the model, the model would have overfit the data.
amplifiers. Half-power amplifier bandpass was 0.1–100 Hz, with
Rather, the selection of sources from among these clusters was
digitizationat250Hz.
basedonrelevantcolor–wordStroopfMRIresearch(Michelet
The following steps were done separately for each participant.
al., 2004). Four of these 14 clusters (LDLPFC, dACC, right
Muscle and other artifact was manually removed with BESA. A
inferior gyrus, left parietal cortex) were used in the source
seriesofstepsweretakentoremoveand/orcorrecteyeblinksand
model(seeFigure1AforfMRIimages).Althoughanalysesfor
movements.Electrodesaboveandbelowtherightandlefteyesand
the present study primarily involved LDLPFC and dACC, the
neartheleftandrightexternalcanthiwereusedtomeasurevertical
full source model included right inferior gyrus, left parietal
and horizontal eye movements. Pairs of channels were used to
cortex, and right parietal cortex to account for variance that is
computebipolarderivations,toidentifyepochsthatincludedeither
a horizontal or vertical saccade. The saccades were marked as thought to be contributed by these sources based on available
artifact periods and removed from the data. A typical blink was literature.TheLDLPFCanddACClocationswereverycloseto
identified in the data. With the pattern search function in BESA, the locations proposed by the cascade-of-control model
the data were scanned to identify other blink periods. Stimulus- (Banich, 2009). Similar studies that have used nonverbal stim-
locked averages were calculated for the experimental conditions uli have also implicated LDLPFC and dACC, suggesting that
(congruent, incongruent, and neutral) for each participant. Only tasks that involve top-down attentional control recruit these
trials with correct responses that occurred 350–1,400 ms after brain regions across stimulus types (Fan, Flombaum,
Table2
FunctionalMRICenterofMassCoordinates(MontrealNeurologicalInstitute)
Region Clustersize Meanz x y z
Leftfrontalorbitalcortex 545 3.76 (cid:5)31 19 (cid:5)8
Rightfrontalorbitalcortex 749 3.61 36 21 (cid:5)6
Leftinferiortemporalgyrus 36 3.36 (cid:5)53 (cid:5)56 (cid:5)15
Leftintracalcarinecortex 111 3.39 (cid:5)8 (cid:5)79 2
Rightthalamus 1,126 3.61 0 (cid:5)16 7
Rightcaudate 67 3.28 11 11 7
Leftputamen 37 3.31 (cid:5)23 (cid:5)2 9
Rightinferiorfrontalgyrus 42 3.35 41 35 13
Leftprecentralgyrus 1,195 3.72 (cid:5)40 11 34
Rightanteriorcingulategyrus 182 3.50 7 21 27
Leftlateraloccipitalcortex 1,376 3.77 (cid:5)35 (cid:5)57 44
Leftprecuneuscortex 443 3.61 (cid:5)5 (cid:5)63 45
Paracingulategyrus 335 3.54 0 14 51
Rightsuperiorparietallobule 132 3.49 39 (cid:5)50 48
Note. Tabledatafrom“TheTimeCourseofActivityinDorsolateralPrefrontalCortexandAnteriorCingulate
CortexDuringTop-DownAttentionalControl,”byR.L.Silton,W.Heller,D.N.Towers,A.S.Engels,J.M.
Spielberg,J.C.Edgar,...G.A.Miller,2010,NeuroImage,50,p.1295.Copyright2010byElsevier.
278 LEVINSILTONETAL.
Figure 1. (A) Left dorsolateral prefrontal cortex (LDLPFC) and dorsal anterior cingulate cortex (dACC)
activationforincongruentversuscongruentstimuli(z(cid:1)3.0902,p(cid:1).01,clustersize(cid:1)34;correctedp(cid:2).05).
Crosshairsplacedatcenterofintensity.(B)FunctionalMRIMontrealNeurologicalInstitute(MNI)coordinates
forsourcemodelcontainingsevenregionalsourcesusedinbrainelectricalsourceanalysissourcemodeling.L(cid:1)
left;R(cid:1)right;RIFG(cid:1)rightinferiorfrontalgyrus;LPC(cid:1)leftparietalcortex;RPC(cid:1)rightparietalcortex;
LOc (cid:1) left occipital cortex; ROc (cid:1) right occipital cortex. Adapted from “The Time Course of Activity in
DorsolateralPrefrontalCortexandAnteriorCingulateCortexDuringTop-DownAttentionalControl,”byR.L.
Silton,W.Heller,D.N.Towers,A.S.Engels,J.M.Spielberg,J.C.Edgar,...G.A.Miller,2010,NeuroImage,
50,p.1296.Copyright2010byElsevier.
McCandliss, Thomas, & Posner, 2003; Liu, Banich, Jacobson, neutral-trial blocks from all psychopathology-free participants
& Tanabe, 2006). (n (cid:1) 66) was used for localizing the visual sources. The epoch
Prior to placing these sources in the model, blink activity was usedforthelocalizationwas100–188ms,spanningprimaryand
modeledasdescribedabove.Next,bilateralvisualcortexsources secondary visual cortex responses. The left and right occipital
(left occipital cortex and right occipital cortex) were localized cortexsourceswereconstrainedtobesymmetrical(seeFigure1B
basedonERPdatafromcorrecttrialsintheneutralcondition.The for left and right occipital cortex coordinates). Finally, the
neutral condition involved the largest number of trials and was LDLPFC, dACC, right inferior frontal gyrus, and left parietal
selected to maximize the signal-to-noise ratio for localization. A cortexsourceswereplacedinthemodelalongwithacontralateral
grandaveragecomputedfromper-subjectwaveformaveragesfor rightparietalcortexsource.Becausemagnitudeofsourceactivity,
DEPRESSION,APPREHENSION,ANDCORTICALACTIVITY 279
ratherthanorientationofsourceactivity,wastheprimaryvariable tation of these moderated mediation models). A series of linear
of interest, all dipoles were converted to regional sources. The regressions were used to test the moderated mediation models.
ERP data were digitally filtered 0.1–12 Hz, and the source Five participants were considered outliers on source measures (3
model was applied separately in each Stroop condition (con- standarddeviationsfromthemeanforatleastonecomponent)and
gruent, incongruent) for each participant. Prestimulus baseline were omitted from subsequent analyses (resulting n (cid:1) 95). The
activity ((cid:5)200 ms to 0 ms) was removed from the source SPSS macro (MODMED) described in Preacher et al. (2007;
waveforms after the model was fit to each participant. Scoring http://www.comm.ohio-state.edu/ahayes)wasusedtoconductthe
windows were based on visual inspection of the source wave- moderationanalyses.
forms as well as taking into consideration findings from rele-
vant scalp- and source-ERP color–word Stroop research. One Results
window for LDLPFC (300–440 ms) and two windows for
dACC (220–340 ms, 520–680 ms) were identified. Source
Behavioral Performance
component amplitude was calculated by averaging data points
24msbeforeand24msafterpeaklatency.Withtheexception RT analyses were conducted to confirm that the Stroop inter-
ofdeterminingthelocationandtemporalscoringwindowofthe ferenceeffectwasobtainedinthepresentsample.Amultivariate
sources, all source analysis steps described above were per- analysis of variance with condition (congruent RT, incongruent
formed separately for each of the 100 participants. RT) and gender confirmed slower RT for incongruent than for
congruent trials: for condition, F(1, 94) (cid:1) 214.10, p (cid:2) .001
Moderated Mediation Analyses (congruent: M (cid:1) 631 ms, SD (cid:1) 95; incongruent: M (cid:1) 791 ms,
SD(cid:1)138).TheStroopeffectdidnotvarybygender.Participants
Moderated mediation analyses (Preacher, Rucker, & Hayes,
mademoreerrorsduringtheincongruentthanthecongruentcon-
2007) were used to evaluate the hypothesis that high levels of dition, F(1, 94) (cid:1) 48.66, p (cid:2) .001 (congruent: M (cid:1) 0.68 errors,
depressionwouldinterferewiththerelationshipbetweenLDLPFC SD (cid:1) 0.95; incongruent: M (cid:1) 2.37 errors, SD (cid:1) 2.22). The
anddACCpreviouslyobservedinthenonclinicalsample(Siltonet
depressionandanxietymeasureswerenotsignificantlycorrelated
al., 2010). In the context of a mediation model, a moderator
withcongruentorincongruentRT,errors,orStroopinterference.
variable is an additional variable that is not part of the causal
sequence that modifies the relationship between two variables
Source-Waveform ERP Moderated Mediation Analysis
(e.g.,independentanddependentvariables).Moderatoreffectsare
alsoreferredtoasinteractions.Continuouspsychopathologyvari-
The ERP source-waveform data analyses (see Figure 3 for
ables(MASQ–AD-8andPSWQscores)wereassignedasmoder-
waveforms) employed scores from incongruent trials only, to
atorstoevaluatewhethertherelationshipsbetweenLDLPFCand
examine the effects of psychopathology within the context of
dACC and between dACC and Stroop interference depended on
cognitivecontrolmechanismspromptedbyStroopconflict.
levelsofpsychopathology(Figure2providesagraphicrepresen- Replicationofcascade-of-controlmodelmediationanalysis.
Priortoproceedingwithmoderationanalyses,themediationanal-
yseswererepeated(seeFigure4),asthesampleselectionproce-
duresvariedfromSiltonetal.(2010).Figure4depictsthemedi-
ation model that was tested. The present sample included
participants recruited from the community, which broadened the
sample, increased the sample size, and included more psychopa-
thology.Themediationanalysesforthecascade-of-controlmodel
were replicated and are presented in Table 3 (see Model 1). The
indirecteffectwasusedtotestdirectlytheoverallsignificanceof
the cascade-of-control model (Preacher & Hayes, 2008). As be-
fore,nowwithasampleexpandedtoincludeparticipantsrecruited
from the community, the indirect effect was significant, and the
cascade-of-control model was supported, with relevant LDLPFC
activity preceding rather than following relevant dACC activity.
Similar to the findings in Silton et al. (2010), the total variance
accountedforwas9%,F(2,92)(cid:1)4.29,p(cid:1).02,whichrepresents
a medium effect size (Cohen, 1992; 9% corresponds to r (cid:1) .30,
whichisstandardforamediumeffectsize).
The influence of psychopathology on the frontocingulate
network:Moderatedmediationanalyses. Itwaspredictedthat
depression would influence the frontocingulate network that is
activatedduringStroopperformance.Depressionwasexpectedto
Figure 2. Moderation models for cascade-of-control model: depression
beassociatedwithreducedLDLPFCactivity,whichinturnwould
(MoodandAnxietySymptomQuestionnaire–AnhedonicDepressioneight-
itemdepressedmoodsubscale)asmoderator(A)andanxiety(PennState influence subsequent dACC activity and related Stroop perfor-
Worry Questionnaire) as moderator (B). LDLPFC (cid:1) left dorsolateral mance. Specifically, the interaction of depression with early
prefrontalcortex;dACC(cid:1)dorsalanteriorcingulatecortex. LDLPFC activity was expected to predict later dACC activity as
280 LEVINSILTONETAL.
Figure3. (A)Grand-averagesourcewaveformsforleftdorsolateralprefrontalcortex(LDLPFC)elicitedduringthe
color–wordStrooptaskforcongruentandincongruentconditions,highlightingthe300–440-msscoringwindow.N(cid:1)
100.(B)Grand-averagesourcewaveformsfordorsalanteriorcingulatecortex(dACC)elicitedduringthecolor–word
Stroop task for congruent and incongruent conditions, highlighting the 220–340-ms and 520–680-ms scoring
windows.N(cid:1)100.From“TheTimeCourseofActivityinDorsolateralPrefrontalCortexandAnteriorCingulate
Cortex During Top-Down Attentional Control,” by R. L. Silton, W. Heller, D. N. Towers, A. S. Engels, J. M.
Spielberg,J.C.Edgar,...G.A.Miller,2010,NeuroImage,50,p.1298.Copyright2010byElsevier.
well as Stroop performance. Given that it was predicted that thesetworegressions,one-tailedtestswereusedtoevaluatethea
depression would alter the relationship between early LDLPFC priorihypothesisdiscussedabove.
andlaterdACCactivity,themodelwithdepressionasamoderator An initial regression tested whether depression influenced the
was tested (see Figure 2) with two hierarchical regressions. For relationship between LDLPFC and dACC during Stroop perfor-
mance. LDLPFC, MASQ–AD-8, and LDLPFC (cid:6) MASQ–AD-8
Table3
SummaryofMediationAnalysesfortheCascade-of-Control
ModelofFigure2
Indirect Regression
effect summary
Model Patha Pathb Pathc Pathc(cid:8) (a(cid:6)b) (R2)
1.Presentstudy 0.44(cid:1) 1.84(cid:1)(cid:1) (cid:5)0.89 (cid:5)1.70(cid:1) 0.81a .09(cid:1)(cid:1)
2.Siltonetal.
(2010) 0.34(cid:1) 1.86(cid:1)(cid:1) (cid:5)1.41 (cid:5)2.00(cid:1)(cid:1) 0.63b .09(cid:1)(cid:1)
Note. Datareflectpathcoefficients.
aSignificant point estimate (p (cid:2) .05): 95% bootstrapped confidence in-
terval [0.11, 1.87], k (cid:1) 5,000. bSignificant point estimate (p (cid:2) .05):
Figure4. Thecascade-of-controlmodel.dACC(cid:1)dorsalanteriorcingu- 95%bootstrappedconfidenceinterval[0.01,1.82],k(cid:1)5,000.
latecortex;LDLPFC(cid:1)leftdorsolateralprefrontalcortex. (cid:1)p(cid:2).10. (cid:1)(cid:1)p(cid:2).05.
DEPRESSION,APPREHENSION,ANDCORTICALACTIVITY 281
werepredictors,andlatedACCactivitywastheDV.Addedlast, A LDLPFC x MASQ-AD-8
LDLPFC (cid:6) MASQ–AD-8 was significant, b (cid:1) (cid:5)0.06, t(91) (cid:1)
30
(cid:5)1.99,p(cid:1).035(one-tailed).Theresultsofthisanalysisshowed
that the interaction of LDLPFC and depression predicted dACC 25
)
activity. The omnibus model accounted for 14% of the variance, m
A
F(3, 91) (cid:1) 4.82, p (cid:2) .01, which corresponds to r (cid:1) .37, repre- n 20
senting a medium effect size (Cohen, 1992). The LDLPFC (cid:6) y (
MASQ–AD-8 interaction accounted for 4% of the total variance vit 15
for this model. Interactions observed in psychological research Acti
typically account for a few percentage points of variance beyond C 10
C
first-ordereffects(Cohen,Cohen,West,&Aiken,2003). A Low MASQ-AD-8
Next,aregressionevaluatedwhethertheinteractionofdepression d 5 High MASQ-AD-8
andLDLPFCpredictedStroopperformancewhenvariancerelatedto
0
dACC was accounted for. LDLPFC, MASQ–AD-8, LDLPFC (cid:6) Low LDLPFC High LDLPFC
MASQ–AD-8, and dACC were predictors, and Stroop interference
wastheDV.Addedlast,theinteractionwassignificant,b(cid:1)(cid:5)0.32, B LDLPFC x MASQ-AD-8
t(90) (cid:1) (cid:5)1.64, p (cid:1) .05 (one-tailed), a finding sufficient for a 250
directional a priori hypothesis. The omnibus model accounted for
15%ofthevariance,F(4,90)(cid:1)3.86,p(cid:2).01,whichcorrespondsto e 200
c
r (cid:1) .39, representing a medium effect size (Cohen, 1992). The n
e
LDLPFC (cid:6) MASQ–AD-8 interaction contributed 3% of the total er 150
varianceforthismodel.Overall,thesefindingsindicatethatdepres- erf
sionandLDLPFCinteracttopredictStroopperformance. p Int 100
In order to better understand the moderating effects of depres- o
o
sion,theinteractionsforbothregressionswereplotted(seeFigures r 50 Low MASQ-AD-8
St
5Aand5B),andthesignificanceoftheslopeswastested(Aiken High MASQ-AD-8
&West,1991).InFigures5A–5C,“low”and“high”referto(cid:3)1 0
standarddeviation(Aiken&West,1991).Importantly,thetestof Low LDLPFC High LDLPFC
simpleslopesisnotatestofaninteractioneffect(theinteractions
are tested in the regression above). Rather, it is a method of C dACC x PSWQ
describing the nature of the interactive relationship (Aiken & 250
West, 1991). High and low are defined relative to the present e
c
sample, and these terms are used to represent two portions of a en 200
r
dimensionratherthanclassificationcategoriesusedtodistinguish e
the absence or presence of clinical diagnoses. The t test for erf 150
nt
whether a simple slope differed from zero was calculated by p I 100
dividing the value of the simple slope by its standard error with o
o
(n(cid:5)k(cid:5)1)degreesoffreedom(wherenisthenumberofcases Str 50 Low PSWQ
andkisthenumberofpredictors).Thestandarderrorwascalcu- High PSWQ
latedfromthevariance–covariancematrixoftheregressioncoef-
0
ficients. As shown in Figure 5A, LDLPFC activity predicted
Low dACC High dACC
dACCactivityatlowlevelsofdepression,t(91)(cid:1)3.69,p(cid:2).001,
but not at higher levels of depression, t(91) (cid:1) 0.54, p (cid:1) .59. Figure5. (A)Leftdorsolateralprefrontalcortex(LDLPFC)(cid:6)Moodand
Furthermore,Figure5BshowsthatLDLPFCactivitywasassoci- Anxiety Symptom Questionnaire–Anhedonic Depression Eight-Item De-
ated with less Stroop interference at higher levels of depression, pressed Mood Subscale (MASQ–AD-8) interaction and tests of simple
t(90) (cid:1) (cid:5)2.28, p (cid:1) .03, but not at low levels of depression, slopes show that at low levels of depression, LDLPFC predicts dorsal
t(90)(cid:1)(cid:5)0.05,p(cid:1).96.Thatis,atlowlevelsofdepression,Stroop anteriorcingulatecortex(dACC).(B)LDLPFC(cid:6)MASQ–AD-8interac-
interference did not vary as a function of LDLPFC activity. For tion,withStroopinterferenceasthepredictorandtestsofsimpleslopes,
individuals higher in depression, LDLPFC and dACC were less shows that at high levels of depression, increased LDLPFC activity is
relatedtolessinterference.(C)dACC(cid:6)PennStateWorryQuestionnaire
well coupled, and LDLPFC activity was more tightly linked di-
(PSWQ)interactionandtestsofsimpleslopesshowthatathighlevelsof
rectlytoRTperformance.
anxiety,increaseddACCisrelatedtogreaterStroopinterference.
Moderated mediation analyses were conducted to evaluate
whetheranxiousapprehensionalsoinfluencedthefrontocingulate
network during Stroop performance (see Figure 2B). Similar in evaluateexploratoryhypotheses.First,aregressionwasconducted
structuretotheregressionanalysesconductedwithMASQ–AD-8, toassesswhetheranxiousapprehensioninfluencedtherelationship
two hierarchical regressions were used to test the influence of betweenLDLPFCanddACC.LDLPFC,PSWQ,andLDLPFC(cid:6)
anxious apprehension on the mechanisms articulated in the PSWQ were predictors, and late dACC activity was the DV. As
cascade-of-controlmodel.Two-tailedsignificancetestswereused predicted,theinteractionwasnotsignificant.Second,aregression
fortheseregressions,becausetheseanalyseswereimplementedto was conducted to evaluate whether anxiety interacted with either