inhibitory control in anxious and healthy adolescents is modulated by incentive and incidental...

Inhibitory control in anxious and healthyadolescents is modulated by incentive and

incidental affective stimuli

Michael G. Hardin,1 Darcy Mandell,1 Sven C. Mueller,1 Ronald E. Dahl,2

Daniel S. Pine,1 and Monique Ernst11Emotional Development and Affective Neuroscience Branch, Mood and Anxiety Disorders Program, National

Institute of Mental Health, NIH/DHHS, USA; 2Departments of Psychiatry and Pediatrics, University of PittsburghMedical Center, USA

Background: Anxiety disorders are characterized by elevated, sustained responses to threat, thatmanifest as threat attention biases. Recent evidence also suggests exaggerated responses to incentives.How these characteristics influence cognitive control is under debate and is the focus of the presentstudy. Methods: Twenty-fivehealthyadolescents and25adolescentsmeetingDSM-IVdiagnostic criteriafor an anxiety disorder were compared on a task of response inhibition. Inhibitory control was assayedwith an antisaccade task that included both incentive (monetary reward) and incidental emotion (facialexpression) cues presented prior to the execution of inhibitory behavior. Results: Inhibitory controlwas enhanced following exposure to threat cues (fear faces) only in adolescent patients, and followingexposure to positive cues (happy faces) only in healthy adolescents. Results also revealed a robustperformance improvement associated with monetary incentives. This incentive effect did not differ bygroup. No interaction between incentives and emotional cueswas detected. Conclusions: These findingssuggest that biased processing of threat in anxious adolescents affects inhibitory control, perhapsby raising arousal prior to behavioral performance. The absence of normalization of performance inanxious adolescents following exposure to positive emotional cues is a novel finding and will requireadditional exploration. Future studies will need to more specifically examine how perturbations inpositive emotion processes contribute to the symptomatology and the pathogenesis of anxietydisorders. Keywords: Emotion, motivation, cognitive control, affective context, anxiety disorders, facialexpressions.

Anxiety disorders are among the most prevalentpsychiatric diagnoses in the pediatric populationand carry a huge individual and societal burden(Costello, Mustillo, Erkanli, Keeler, & Angold,2003). Over the past 20 years, research has fo-cused on the role of cognition in the developmentand maintenance of these disorders (Beck & Clark,1997; Ehrenreich & Gross, 2002; Eysenck, 1992;Eysenck, Derakshan, Santos, & Calvo, 2007).Much of this research has targeted selectiveattention to threat-related information. Because ofthis specific focus on threat processing in anxiety,less work has been devoted to questions thatconcern the processing of positively valencedstimuli, such as rewards or cues signaling positiveemotion. Even less work examines the influence ofthese emotional stimuli on cognitive control inpediatric anxiety. The present work was designedto examine these issues.Recent investigations of reward systems and

incentive processing provide some insights intoadolescent anxiety. Although very few studies have

been conducted, early findings suggest the occur-rence of hypersensitivity to incentives in pediatricanxiety disorders. For example, behavioral researchconducted with exceptionally shy and anxiouscollege students has indicated they respond fasterto potential rewards compared to their demo-graphically matched peers during a monetaryincentive delay (MID) task (Hardin et al., 2006).This report has been further supported by twoparallel functional neuroimaging studies. Using thesame MID task, additional studies examined theneural response to potential rewards in adolescentswith an anxiety disorder (Guyer at al., in prep),and adolescents at high risk for an anxiety disor-der by virtue of a behaviorally inhibited tempera-ment (Guyer et al., 2006). Both anxious andbehaviorally inhibited adolescents in these studiesshowed greater reward system (i.e., ventral stria-tum) engagement in response to incentives com-pared to age- and sex-matched typical adolescents.Finally, recent evidence also suggests incentivesmodulate cognitive control performance in bothanxious and healthy adolescents (Hardin, Schroth,Pine, & Ernst, 2007; Jazbec, McClure, Hardin,Pine, & Ernst, 2005), though it remains unclearConflict of interest statement: No conflicts declared.

Journal of Child Psychology and Psychiatry 50:12 (2009), pp 15501558 doi:10.1111/j.1469-7610.2009.02121.x

2009 The AuthorsJournal compilation 2009 Association for Child and Adolescent Mental Health.Published by Blackwell Publishing, 9600 Garsington Road, Oxford OX4 2DQ, UK and 350 Main Street, Malden, MA 02148, USA

whether differences occur in the effect of incentiveson cognitive control in anxious relative to healthyadolescents.Whereas hypersensitivity to incentives engages

neural mechanisms involving striatal circuits,responses to affective cues typically recruit a differentneural network. The typical network recruited byaffective stimuli also involves the amygdala, and thusmodulates cognitive performance via a differentneural path than incentives (Davis & Whalen, 2001;Vuilleumier, 2005). While striatum and amygdalacentered networks appear to have a dominantrole related to distinct processes involvingincentives and affect, respectively, other processes dosimultaneously recruit both networks. For example,amygdala recruitment is sometimes reported inreward-processing studies (see Holland & Gallagher,2004; Murray, 2007), while striatal involvementoccurs during the coding of negative emotional events(see Delgado, Li, Schiller, & Phelps, 2008).Theories of anxiety suggest that threat-related

affective cues raise states of arousal dispropor-tionally to the level of actual danger (see Beck &Clark, 1997; Ehrenreich & Gross, 2002; Mogg &Bradley, 1998). When threat cues precede behav-ioral responses, elevated levels of arousal and vig-ilance are associated with facilitated attention andorienting responses (i.e., Bar-Haim, Lamy, Perg-amin, Bakermans-Kranenburg, & van IJzendoorn,2007; Dalgleish et al., 2003; Ehrenreich & Gross,2002; Mogg & Bradley, 1998) that include cognitivecontrol processes (see Corbetta & Shulman, 2002;Miller & Cohen, 2001). In contrast, when threatcues occur during or simultaneously to perfor-mance responses, the behavior becomes negativelyimpacted. Indeed, co-occurring threat cues canproduce interference with cognitive processes andlead to performance decrements (i.e., Bishop,2008; Williams, Mathews, & MacLeod, 1996).Much less is known about the influence of positiveemotional cues in anxiety. Data in healthy subjectssuggest that positive emotion cues enhance cogni-tive processes (Rowe, Hirsh, & Anderson, 2007).Whether positive emotion modulates cognitivefunction differentially in anxious individuals is notclear.The current study was concerned with the

influence of incentive and affective stimuli pre-sented prior (and not simultaneously) to behavioralresponses. For this reason highly salient stimuliwere expected to facilitate responses. Evidencefrom non-human primate studies examining cog-nitive control (response inhibition) indicate thatincreased neural arousal (i.e., increased cell firing)during a preparatory period, prior to a requiredbehavioral response, facilitates successful inhibi-tory control (see Munoz & Everling, 2004). Like-wise, presentation of salient stimuli during thepreparatory period correspond with increasedneural arousal and performance (see Hikosaka,

2007). Given the neural arousal observed duringthe processing of salient stimuli in human neuroi-maging studies (i.e., Davis & Whalen, 2001;Knutson, Adams, Fong, & Hommer, 2001; Knutson& Cooper, 2005; Vuilleumier, 2005), presentationof salient stimuli during the response prepa-ration period in the current study was expected tocorrespond with increased cognitive control andcorresponding performance.Taken together, evidence of incentive hypersensi-

tivity and of affective processing biases in anxietyraises the question of how these two unique moti-vational/affective processes interact to influencecognitive function and subsequent behavior. Thegoal of the present study was to address thisquestion. This study examined how incentive cuesand incidental, task-irrelevant, affective cuesinfluence the performance of anxious and healthyadolescents on an inhibitory control task. Of note,and important to the generation of hypotheses, bothincentive and emotion cues in this task werepresented prior to cognitive performance, ratherthan simultaneously with cues requiring executionof a response. Based on enhanced reward responses(Hardin et al., 2007; Jazbec et al., 2005) andemotion biases reported in anxious individuals(Bar-Haim et al., 2007), the following patterns ofinhibitory performance were predicted: (1) incentive-related improvements for both anxious and controladolescents, with relatively greater improvements inanxious compared to control adolescents; (2) rela-tively greater improvements related to incidentalthreat cues for anxious adolescents compared tocontrol adolescents; and (3) improvements relatedto incidental positive emotion cues in both anxiousand control adolescents.

Methods

Participants

Participants were 25 (13 female) adolescents diag-nosed with an anxiety disorder (M = 12.65 years,SD = 2.35 years), and 25 (12 female) age-matchedhealthy, typically developing adolescents(M = 13.21 years, SD = 2.39 years). All participantswere medication free at the time of the study. Of theanxious adolescents, 13 had a primary diagnosis ofsocial phobia, and 12 generalized anxiety disorder(GAD). Two adolescents with GAD had a co-morbiddiagnosis of major depressive disorder. Participantswere recruited through local newspaper advertise-ments and word of mouth. The study was approvedby the National Institute of Mental Health Institu-tional Review Board. The parents of all participantsgave informed consent, and adolescent participantsprovided informed assent.Inclusion criteria for healthy adolescents included:

(1) age between 9 and 17 years; (2) absence of acuteor chronic medical problems; and (3) absence ofcurrent or past psychiatric disorders. Inclusion criteria

Incentive and affect modulation of inhibitory control in adolescent anxiety 1551

2009 The AuthorsJournal compilation 2009 Association for Child and Adolescent Mental Health.

for anxious adolescents included: (1) primary diagnosisof an anxiety disorder based on a semi-structureddiagnostic interview (K-SADS; Kaufman et al., 1997); (2)Childrens Global Assessment Scales score < 60 (CGAS;Shaffer et al., 1983); (3) Pediatric Anxiety Rating Scalescore > 9 (RUPP, 2001); (4) desire for outpatienttreatment; and (5) age between 9 and 17 years.Exclusion criteria for all participants included: (1)current use of any psychoactive substance; (2) currentTourettes syndrome, obsessive-compulsive disorder,post-traumatic stress disorder (PTSD), conductdisorder, exposure to extreme trauma, or suicidalideation; (3) lifetime history of mania, psychosis, orpervasive developmental disorder; or (4) IQ < 70. Alladolescent diagnoses were based on semi-structuredinterviews using the K-SADS. Interviews were con-ducted by experienced clinicians who demonstratedexcellent inter-rater reliability (j > .75). Additionalself-report anxiety measures were collected with theState-Trait Anxiety Inventory (STAI; Spielberger, 1983),and self-report depression measures were collected withthe Childrens depression Inventory (CDI; Helsel &Matson, 1984; Kovacs, 1982). See Table 1.

Incentive Emotion Antisaccade Task (Figure 1)

The Incentive Emotion Antisaccade Task (IEAT) wasdesigned to assess inhibitory cognitive control of anti-saccade eye movements in two explicitly presentedIncentive conditions (Reward, No Reward). Eachincentive condition was paired with three face Emotionconditions (Happy, Fear, Neutral). This design permit-ted us to examine how cognitive control was modulatedby incentives, by incidental affective cues, and by theinteraction of both incentives and affective cues inanxious and healthy adolescents.Task trials were comprised of three phases (Figure 1):

(1) the cue phase (1,2501,750 ms) informedparticipants of the Incentive condition; (2) the targetantisaccade response phase (1,850 ms); and (3)the feedback phase (1,000 ms). Participants wereinstructed to fixate the Incentive condition cue duringthe cue phase, to respond with an antisaccade eyemovement during the response phase, and to fixatethe performance feedback symbol during the feedbackphase. A relatively long duration of the cuephase (average 1,500 ms) was chosen to maximizeincentive and affective stimulus exposure during theresponse preparation period. The relatively long dura-tion of the antisaccade response phase was chosen tomaximize this paradigm for future neuroimagingstudies. Despite the long duration of the responsephase, analyses were restricted to saccade responsesthat occurred less than 500 ms after target onset.Each task trial began with the presentation of one of

two possible Incentive cues. Each of these Incentivecues was superimposed on an Emotion condition face.The Emotion face was centered on a black computerscreen and subtended 2.5 horizontal and 4 vertical.The Incentive cue was located at the center horizontaland 1 above the vertical center of the computer screen.This location placed the Incentive cue approximately onthe center forehead of the Emotion face images.Participants were instructed to fixate the Incentive cue.Incentive cues subtended 1. Potential monetary

Reward was cued by a $ in black font, while No Rewardwas cued by a O in black font.Emotion faces appeared concurrently with the

Incentive cues, but transferred no task-related infor-mation to the participant (i.e., task-irrelevant). TheEmotion faces consisted of black and white portraits ofactors from the NimStim set of Facial Expressions(http://www.macbrain.org/resources.htm). Facialemotion included happy, fearful, and neutral emotionexpressions from 24 different actors (12 female, 12male).Following a variable period of 1,2501,750 ms, the

Incentive cue and simultaneously occurring Emotionface were replaced by a lateral target stimulus thatremained on the screen for 1,850 ms. The target was a* presented in white font and subtending .5. Thetarget appeared at the vertical center and 6 fromcenter to the left or right horizon. The participant wasrequired to fixate for 100 ms minimum in an area of 1radius around the correct target location to succeed ona trial.The target was replaced by a feedback signal in the

correct response location. In the Reward conditionfeedback was $1.00 presented in green font for a cor-rect response, and $1.00 presented in red font for anincorrect response. Feedback in the No Reward condi-tion was $0.00 presented in green font for a correctresponse and red font for an incorrect response. TheIEAT task consisted of 144 trials total (24 per condi-tion), and was presented in four runs of 36 trials. Allconditions were randomly presented. Participants weretrained on the tasks prior to study participation, andwere instructed that they would receive the dollaramount won during the task.

Eye movement recording

Eye movements were recorded with an ASL Model 504eye tracking system (Applied Science Laboratories,Boston, MA) at 240 Hz temporal resolution and .25spatial resolution. A magnetic head tracker and autofocusing lens were used to minimize head movementartifact. Raw eye movement data was analyzed off-linewith ILAB software (Gitelman, 2002). Saccades weredefined as movements greater than 30/second thatlasted for a minimum duration of 25 ms. Whendetermining correct and incorrect movements, onlythe first saccade following onset of the target stimuluswas considered. Saccade accuracy was indexed as thepercent of saccades directed to the correct location(opposite periphery of the target). Saccade latency was

Table 1 Mean (SD) demographic information for Healthy andAnxious adolescent groups

Healthy Anxiety

Age 13.21 (2.39) 12.62 (2.35)Sex 12F/13M 13F/12MTanner Stage 2.32 (1.20) 2.42 (1.34)IQ 117.42 (8.99) 111.57 (12.76)CDI 42.22 (5.78) 49.75 (7.02)STAI* 26.56 (5.16) 37.80 (5.91)

*significant group difference, p < .05.

1552 Michael G. Hardin et al.


the time elapsed between target onset and the start ofa saccade. To ensure task-relevant saccades wereanalyzed, analyses were restricted to saccadesoccurring 80500 ms after target onset.

Data analyses

Analyses were conducted to assess Group (healthyadolescents; anxious adolescents), Incentive condition(Reward, No Reward), and Emotion condition (Happy,Fear, Neutral) effects on inhibitory control during theIEAT. Inhibitory control was operationally defined bythe percent of correct antisaccades (saccade accuracy)and reaction time for correct antisaccades (saccadelatency). Accuracy was considered a metric of effec-tiveness, providing an index of the overall quality oftask performance (Eysenck et al., 2007). Latency wasconsidered a metric of the efficiency of performance,providing an index of how correct responses were made.The mapping of these variables onto the constructs ofeffectiveness and efficiency has been validated inprevious studies employing antisaccade tasks (Ansari,Derakshan, & Richards, 2008; Derakshan, Ansari,Hansard, Shoker, & Eysenck, 2009). A 3-way (Group Emotion Incentive) repeated-measures ANOVA wasconducted for each of these two dependent variables. Allpost hoc comparisons were Bonferroni corrected and atwo-tailed alpha level of .05 was used for all significancetests.

Results

Accuracy (index of performance effectiveness)

The 3-way ANOVA conducted on accuracy scoresrevealed no Group differences. Across Incentive andEmotion conditions, healthy andanxious adolescents

did not differ on percent of correct antisaccades(healthy adolescents:M = 85.8%,SE = 2.1%; anxiousadolescents: M = 81.0%, SE = 2.1%), F(1,48) = 2.51,p = .12).However, a main effect of Incentive emerged. All

adolescents were more accurate in the Rewardcondition (M = 84.8%, SE = 1.5%) than the No Re-ward condition (M = 79.89%, SE = 1.5%), F(1,48) =18.80, p < .001) (Figure 2). No accuracy differencesemerged among Emotion conditions.

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Figure 1 Schematic representation of the Incentive Emotion Antisaccade Task (IEAT). During the Cue phase,participants viewed an incentive cue (signaling the prospect of either wining or losing an incentive, or no-incentive)that was superimposed on a task-irrelevant emotion face). In the Anti-saccade Response phase a peripheral targetappeared and the participant responded by looking to the opposite side (antisaccade) as the target. During theFeedback phase, the participants received the outcome of their response (won or lost money for incentive condition;won or lost no money for no-incentive condition)

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Figure 2 Mean (SE) percent of correct antisaccadesduring Reward and No Reward conditions in healthyand anxious adolescents



To summarize the accuracy findings, neither thestatus of anxiety nor the presence of incidentalemotion stimuli modulated task accuracy. However,as expected from previous work, inhibitory perfor-mance improved with incentive for both adolescentgroups.

Latency (index of performance efficiency)

The three-way ANOVA conducted on latency tocorrect antisaccades revealed a Group by Emotioninteraction, F(2,96) = 3.67, p < .05 (Figure 3). Thisinteraction was the result of anxious adolescentsperforming most efficiently in the Fearful emotioncondition, in contrast to healthy adolescents, whoperformed most efficiently in the Happy emotioncondition. Anxious adolescents presented a shorterlatency in the Fear condition (M = 283.88) com-pared to the Neutral (M = 324.42) or Happy(M = 322.92) conditions. In contrast, healthy ado-lescents presented a shorter latency in the Happy(M = 279.65) condition compared to the Neutral(M = 310.89) or Fear (M = 301.97) conditions (seeTable 2). To more clearly illustrate this interaction,

Figure 4 presents these latencies as a ratio of theneutral condition to the Happy and Fear conditions.In this figure, a ratio equal to1 represents latencyequivalence between the neutral condition and theemotion condition. Ratio values greater than 1represent higher response efficiency (relative tothe neutral condition), while values less than 1represent lower response efficiency.. As apparent inthis figure, the greatest increase in antisaccadeefficiency for healthy adolescents occurred duringthe Happy face condition, and for anxious adoles-cents during the Fear face condition.Similar to the accuracy results, a main effect of

Incentive was also present, F(1,48) = 5.62, p < .05.Performance in both groups was more efficient, aslatency during the Reward condition (M = 292.44,SE = 15.89) was significantly shorter than in the NoReward condition (M = 315.48, SE = 14.68). Thisfacilitation by Incentive was independent of theEmotion condition (no significant Incentive byEmotion interaction). No additional main or inter-action effects were present in latencies.To summarize the latency findings, anxiety status

was associated with a distinct sensitivity to inci-dental emotion cues. Specifically, efficiency of inhi-bition was facilitated by threat cues in anxiousadolescents, and by positive emotion cues in healthyadolescents. Additionally, reward cues facilitatedinhibitory control for both anxious and healthyadolescents.

Discussion

Anxiety disorders are associated with threatattention biases (Bar-Haim et al., 2007; Roy et al.,2008; Williams et al., 1996) and an exaggeratedresponse to incentives (Hardin et al., 2007; Jazbecet al., 2005). How these perturbations interact withcognitive control, particularly inhibitory control,can be of critical importance not only for under-standing the pathogenesis of anxiety disorders, butalso to provide rational therapeutic interventions.The present study was designed to address ques-tions concerning the influence of emotion andincentive stimuli on inhibitory control. Forthis purpose, the current study examined the

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Figure 3 Mean (SE) latency for correct antisaccadesduring incidental Neutral, Happy, and Fear face con-ditions in healthy and anxious adolescents

Table 2 Mean (SD) percentage of correct antisaccades, and mean (SD) latency (ms) of correct antisaccades in Reward and NoReward conditions by Neutral, Happy, and Fear face conditions

Reward No Reward

Neutral Happy Fear Neutral Happy Fear

Accuracy %Healthy 86.12 (10.72) 89.17 (9.84) 86.17 (11.45) 83.50 (11.37) 84.67 (10.73) 85.00 (11.53)Anxious 82.33 (13.78) 83.14 (12.42) 81.67 (11.02) 81.58 (12.40) 80.06 (13.32) 77.47 (12.07)

LatencyHealthy 302.05 (129.70) 280.61 (129.09) 277.47 (109.50) 319.73 (124.26) 278.69 (123.41) 326.46 (119.35)Anxious 310.40 (131.88) 323.70 (163.40) 260.36 (78.85) 338.43 (140.72) 322.13 (120.86) 307.40 (143.75)



performance of anxious and healthy adolescents onan antisaccade eye movement task that was pairedwith monetary incentives and emotion cues.Two primary findings resulted from this study.

First, incidental emotional cues, that werepresented prior to inhibitory performance in eachtask trial, influenced cognitive control differentiallyas a function of diagnosis. Inhibitory performancefollowing positive emotion stimuli (happy faces)was improved only for healthy adolescents. Con-trary to expectations, anxious adolescents failed toshow this pattern of improved performance follow-ing positive stimuli. Anxious adolescents, however,did show improved performance after the presen-tation of threat stimuli (fearful faces), whereashealthy adolescents did not show this threat-related pattern. Second, in line with predictionsand previous findings, incentives enhanced inhibi-tory control in both anxious and healthy adoles-cents. However, contrary to hypotheses thiscognitive enhancement by incentives did not differbetween groupsIn this study, we were particularly interested in

the influence that affective and incentive cues haveon inhibitory control when presented prior toresponse execution (i.e., during response prepara-tion). This approach differs from previous studies,which focused on the interfering effect of salientstimuli, and presented salient stimuli duringresponse execution. Contrary to these previousstudies, which predicted impaired cognitive andbehavioral responses based on interference effects,the current study predicted an enhanced responsebased on arousal effects. Indeed, we predictedperformance enhancement secondary to increasedstimulus-driven arousal that occurs when salient

stimuli are presented during the response prepa-ration period.The current findings revealed that healthy ado-

lescents showed the predicted improvement ininhibitory performance following presentation ofhappy faces. However, this normative effect ofpositive emotional stimuli was absent in anxiousadolescents. This finding has strong theoreticalimplications as it may reflect a deficiency for anx-ious adolescents in the processing of facial displaysof positive emotion. Recent work conducted withanxious individuals provides additional support forthis possibility. For example, anxious young adultslack the bias seen in healthy young adults to judgefacial displays of moderate happiness as morepositive than they are in actuality (Frenkel, Lamy,Algom, & Bar-Haim, 2008). Instead, these anxiousyoung adults judge displays of moderate happinessas being much less happy (Frenkel et al., 2008).Similarly, whereas healthy adults overestimate theprediction for positive outcomes following exposureto happy faces, adults with social anxiety show adeficit in this positive bias (Garner, Mogg, & Brad-ley, 2006). Overall, these findings suggest thathappy emotion faces may not hold the same levelof salience for anxious individuals as they do fornon-anxious individuals.While the literature on emotion processing in anxi-

ety has traditionally focused on threat, the currentfindings suggest additional deficits exist inprocessingpositive emotional stimuli. Likewise, it appears thatmodels based solely on threat processing biases onlyprovide a partial account of the processes underlyinganxiety. Future work will be required to better char-acterize positive-affect-related deficits in anxiousadolescents. It will be particularly important to

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Figure 4 Mean (SE) latency for Happy face and Fear face conditions when normalized to the Neutral condition. In thisfigure, a latency difference greater than one represents an efficiency increase relative to the Neutral condition



evaluate this deficit with both social and non-socialaffective stimuli, as well as in various subtypes ofanxiety (social anxiety for example). Likewise, it iscurrently unclear whether the deficits displayed byanxious adolescents results from perceptualprocessing deficiencies or from deficiencies in theamount of arousal generated by positive emotionalstimuli. It will be important for future models ofanxiety-related processes to integrate findings ofdeficient positive emotion processing.The current findings are consistent with our initial

proposition that anxious adolescents would showfacilitated performance following threat cues. Whenlooking at within-group difference in responselatency, anxious adolescents showed significantlymore efficient inhibitory control following threatcues relative to neutral or happy face cues. A similarthreat-related effect was not observed in the healthyadolescents. As a caveat, however, groups did notdiffer in the absolute effect of threat cues.When takentogether these within-group and between-groupdifferences indicate that the facilitation of inhibitoryefficiency by threat cues in anxious adolescents aidthem in overcoming an initial efficiency deficit, andraises inhibitory efficiency to the level of healthyadolescents.The beneficial effect of incentives was significant

for both accuracy and latency measures. Thisfinding is consistent with previous work employingsimilar antisaccade paradigms (i.e., Hardin et al.,2007; Jazbec et al., 2005), and may be mediated bya facilitating influence of motivational arousal oninhibitory control processes. The underlying neuralmechanisms are suggested to involve bottom-up(stimulus-driven) modulation, by which incentivesactivate meso-striatal cortical loops (Cardinal,Parkinson, Hall, & Everitt, 2002; Schultz, 2006),which in turn enhance the signal-to-noise ratio ininhibitory circuits and result in enhanced inhibitoryperformance. Performance improvements wereobserved in both the effectiveness (accuracy) andefficiency (latency) measures, arguing for a robusteffect (Ansari et al., 2008; Derakshan et al., 2009).The failure to detect a stronger effect of incentivesin anxious relative to healthy adolescents could berelated to the structure of the paradigm. Indeed,compared to previous antisaccade tasks that haveexamined the influence of incentives only, thepresent task included the additional manipulationof incidental emotional stimuli. This change mighthave mitigated a diagnosis effect, and will requirefurther examination.While the findings concerning incentive-related

enhancement of inhibitory control have focused onthe rewarding aspect of the incentive condition, aninfluence by the punishing aspect of the incentivecondition cannot be ruled out. The bivalent natureof the incentive condition in this study was basedon previous behavioral findings that implicatedimproved performance following cues signaling

either winning or not winning, and cues signalingeither losing or not losing (i.e., Hardin et al.,2007). The current finding raises the interestingpossibility that the incentive-related findings weredriven by the fear of losing rather than the lure ofa gain.This study should be considered in light of the

following limitations. First, the heterogeneity ofanxiety disorders precludes any conclusions aboutdiagnostic specificity. For completeness, a com-parison between the patients with a primary diag-nosis of social anxiety (n = 13) and those with aprimary diagnosis of generalized anxiety disorder(n = 12) failed to reveal significant group differ-ences, either as a main effect or in interaction withincentives or emotion cues. This negative findingmay reflect the fact that, collectively, anxietydisorders represent a distinct diathesis, which ischaracterized by unique deficits, in threat bias andresponses to positive stimuli. However, how eachdisorder manifests these deficits in specific waysremains an important question to examine infuture work. Second, our relatively small samplesize did not permit us to examine age or sex effectswith sufficient statistical power. Third, the signifi-cance of the findings as primary or secondarymanifestations of anxiety cannot be determined inthis work. Studies of at-risk populations could helpin this respect.In summary, findings from the current work

indicate that response inhibition in both anxiousand healthy adolescents is modulated by monetaryincentives. Additionally, incidentally presentedaffective stimuli differentially modulate responseinhibition in anxious and healthy adolescents.Anxious adolescents appear to be deficientcompared to healthy adolescents in the influence ofpositive emotion faces on inhibitory control.Additionally, anxious adolescents show abnormallyhigh efficiency of response inhibition followingnegative affective stimuli. These findings need tobe further explored via functional neuroimagingmethods.

Acknowledgements

This research was supported by the Intramural Re-search Program of the National Institutes of Health.We would like to thank Harvey Iwamoto for his pro-gramming assistance.

Correspondence to

Michael G. Hardin, Emotional Development andAffective Neuroscience (EDAN) Branch, Moodand Anxiety Disorders Program, NIMH/NIH/DHHS,15K North Drive, Bethesda, MD 20892, USA;Tel: 301.594.1257; Fax: 301.402.2010; Email:[email protected]



Key points

Anxiety disorders are characterized by biased responses to threat stimuli, and recent evidence ofenhanced responses to incentive-related stimuli.

Despite involvement of cognitive control processes in emotion and incentive-related responses, little isknown about the influence of these stimuli on cognitive control processes.

The current study suggests an anxiety-related deficit in the normal enhancement of cognitive control bypositive emotional stimuli.

Anxiety-related enhancement of cognitive control following threat stimuli also occurs and may result fromincreased threat-related arousal.

Like non-anxious adolescents, anxious adolescents show enhanced cognitive control with incentivestimuli.

Understanding the interaction between processing salient stimuli and regulatory cognitive control pro-cesses can provide insight into the onset and maintenance of anxiety disorders, and guide futurebehavioral treatment approaches.

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Manuscript accepted 30 April 2009



inhibitory control in anxious and healthy adolescents is modulated by incentive and incidental...

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