A neurobehavioral account for individual differencesin resilience to chronic military stress

T. Lin1,2, S. Vaisvaser1,3, E. Fruchter4, R. Admon1, I. Wald2, D. S. Pine5, Y. Bar-Haim2,6 andT. Hendler1,2,3,6*

1Functional Brain Center, Wohl Institute for Advanced Imaging, Tel Aviv Sourasky Medical Center, Israel2School of Psychological Sciences, Tel-Aviv University, Israel3Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Israel4Division of Mental Health, Medical Corps, IDF, Tel Hashomer, Military Mail, Israel5Mood and Anxiety Disorders Program, Intramural Research Program, The Institute of Mental Health, Bethesda, MD, USA6Sagol School of Neuroscience, Tel Aviv University, Israel

Background. Military training is a chronic stressful period that often induces stress-related psychopathology. Stressvulnerability and resilience depend on personality trait anxiety, attentional threat bias and prefrontal–limbic dysfunction.However, how these neurobehavioral elements interact with regard to the development of symptoms following stressremains unclear.

Method. Fifty-five healthy combat soldiers undergoing intensive military training completed functional magneticresonance imaging (fMRI) testing while performing the dot-probe task (DPT) composed of angry (threat) and neutralfaces. Participants were then stratified according to their bias tendency to avoidance (n = 25) or vigilance (n = 30) groups,categorized as high or low trait anxiety and assessed for post-stress symptom severity.

Results. Avoidance compared to vigilance tendency was associated with fewer post-trauma symptoms and increasedhippocampal response to threat among high anxious but not low anxious individuals. Importantly, mediation analysisrevealed that only among high anxious individuals did hippocampal activity lead to lower levels of symptoms throughavoidance bias tendency. However, in the whole group, avoidance bias was modulated by the interplay between thehippocampus and the dorsal anterior cingulate cortex (dACC).

Conclusions. Our results provide a neurobehavioral model to explain the resilience to post-trauma symptoms followingchronic exposure. The model points to the importance of considering threat bias tendency in addition to personality traitswhen investigating the brain response and symptoms of trauma. Such a multi-parametric approach that accounts forindividual behavioral sensitivities may also improve brain-driven treatments of anxiety, possibly by targeting theinterplay between the hippocampus and the dACC.

Received 4 February 2014; Revised 17 July 2014; Accepted 25 July 2014

Key words: dACC deactivation, hippocampal activity, PTSD symptoms, threat bias, trait anxiety.

Introduction

Military training is an intense and stressful period dur-ing which individuals are exposed to a combination ofdangerous stressful events on a daily basis (Berntonet al. 1995), thus representing a well-defined period ofchronic stress (Day & Livingstone, 2001) that may im-pact the development of stress-related symptoms suchas anxiety and depression (Morgan, 2001; Taylor et al.2007). A detailed neurobehavioral characterization ofindividuals experiencing realistic intense stress may

enhance our understanding of the development ofthese symptoms.

Stress vulnerability and resilience have been asso-ciated with trait anxiety (McFarlane, 1990), patterns ofattention to threat (Bar-Haim et al. 2007; Wald et al.2013) and limbic and prefrontal cortex (PFC) function(Admon et al. 2009, 2013b). These factors also interactwith each other: threat attentional bias has been relatedto trait anxiety (MacLeod & Mathews, 1988; Mogg et al.1994), and with the interplay between limbic and PFCfunction, which is unbalanced in stress-related disor-ders (Bishop, 2007, 2008). However, the relationshipsbetween trait anxiety, threat bias and brain activityand their contribution to the severity of stress-relatedsymptoms remain unclear.

A common approach to measuring threat-relatedattention bias is the dot-probe task (DPT; Mogg &

* Address for correspondence: T. Hendler, Wohl Institute forAdvanced Imaging, Tel-Aviv Sourasky Medical Center, 6 WeizmannStreet, Tel-Aviv 64239, Israel.

(Email: hendlert@gmail.com) [T. Hendler](Email: tamarlin@gmail.com) [T. Lin]

Psychological Medicine, Page 1 of 13. © Cambridge University Press 2014doi:10.1017/S0033291714002013

ORIGINAL ARTICLE

Bradley, 1999; Monk et al. 2006; Bar-Haim et al. 2007;Fani et al. 2012). This task simultaneously presentspairs of threat-neutral stimuli, followed by a probethat requires a response. The probe replaces a threatstimulus in threat-congruent trials or a neutral stimu-lus in threat-incongruent trials. Participants can bestratified into those who tend to respond faster tocongruent relative to incongruent trials, preferentiallydirecting attention towards threat cues (vigilance biastendency), and those who tend to respond faster to in-congruent relative to congruent trials, preferentiallydirecting attention away from threat cues (avoidancebias tendency) (Price et al. 2011; Waters et al. 2012).Behavioral studies using the DPT typically find vigil-ance bias in high trait anxious individuals and in clini-cal populations including patients with post-traumaticstress disorder (PTSD; Bradley et al. 1999; Bar-Haimet al. 2007; Fani et al. 2012).

Imaging studies report that threat bias involves lim-bic regions including the amygdala, the hippocampusand PFC areas, including the anterior cingulate cortex(ACC) and lateral PFC (lPFC) (Bishop et al. 2004;Monk et al. 2006; Bishop, 2008; Telzer et al. 2008;Vollstädt-Klein et al. 2012; Fani et al. 2013). Together,these limbic and prefrontal regions encompass amajor part of the stress-related neural circuit thatmay affect threat processing and anxiety (Mogg et al.1990; Dedovic et al. 2009).

The role of the amygdala in this task may be relatedto rapid tagging of threat cues (Ledoux & Muller,1997). Amygdala activity during threat processinghas been shown to be predicted by individual differ-ences in trait anxiety (Etkin et al. 2004). Moreover,amygdala activity before stress predicted an increasein post-trauma symptoms (Admon et al. 2009). Thehippocampus, however, may be involved in processingthreat context during probe detection (Sanders et al.2003) and monitoring the levels of threat to controlbehavioral inhibition, such as avoidance behavior(Bach et al. 2014). Indeed, a recent dot-probe study re-lated the neural activity of the hippocampus to threatavoidance in clinically anxious youth (Price et al.2014). Within the context of threat, hippocampal ac-tivity has been suggested to play a role in mediatingtrait anxiety (Satpute et al. 2012) and has been asso-ciated with PTSD (Shin et al. 2006). Additionally, hip-pocampal plasticity has been related to stressvulnerability (Admon et al. 2009, 2013b). Finally, thelPFC may be important for allocating attention(Egner & Hirsch, 2005) and the ACC for conflict moni-toring and threat appraisal (Kerns et al. 2004; Etkinet al. 2011), all of which are important in threat-processing tasks such as the DPT. Akin to the limbicregions, activity in these prefrontal regions has beenassociated with trait anxiety (Bishop, 2009; Klumpp

et al. 2011), and disrupted function in the ACC hasbeen implicated in PTSD (Shin et al. 2001, 2006) andassociated with vulnerability to such psychopathology(Shin et al. 2011; Admon et al. 2013b).

Thus, several lines of research indicate that atten-tional threat bias is related to trait anxiety and clinicalanxiety including PTSD and that limbic and prefrontalregions are associated with trait anxiety, threat biasand PTSD. However, two key questions remain unre-solved. First, does threat bias interact with trait anxietyto influence stress-related symptoms? Second, is thisrelationship reflected in specific brain responses? Toaddress these open issues, we combined measure-ments of trait anxiety, behavioral threat bias in theDPT, neural reactivity to threat and PTSD symptomsin combat soldiers following 1 year of intense militarytraining. Specifically, we recruited soldiers from anelite combat unit undergoing a prolonged trainingcourse, which is among the most difficult and rigoroustraining programs in the Israel Defense Forces (IDF).We hypothesized that individuals with high trait anxi-ety and avoidance bias would have fewer PTSD symp-toms than individuals with high trait anxiety andvigilance bias. From a neural perspective, we assumedthat threat stimuli in the context of emotional conflictduring the DPT would engage the amygdala, hippo-campus, ACC and lPFC. We further assumed thatonly among high trait anxious individuals wouldavoidance and vigilance biases show a differential pat-tern of limbic and prefrontal activity, which would berelated to differences in PTSD symptoms.

Method

Participants

Participants were 55 male IDF soldiers (mean age18.87 ± 0.92 years) trained in an elite combat unit.Participants were recruited to the study after 1 yearof intensive and advanced combat training. Duringmilitary training, participants were exposed to awide variety of stressful physical and psychologicaldemands that have been shown to affect well-being,including sleep restrictions, prolonged periods ofphysical survival challenges, face-to-face combattraining and a counter-terrorism combat course(Gomez-Merino et al. 2005). Participants were askedto complete a questionnaire with several items regard-ing life history of traumatic and significant experiencesand illnesses. These included specific questions regard-ing any severe mental and/or physical illnesses, and/orhospitalizations of the participant and their close fam-ily, along with an open question in which participantswere asked to describe any traumatic and/or signifi-cant experience that occurred throughout their civilian

2 T. Lin et al.

life prior to their military service. According to this,participants had no reported history of psychiatric orneurological disorders, no current use of psychoactivedrugs, no family history of major psychiatric disorders,and no incidence of childhood abuse or potentiallytraumatic events before military enrollment. All parti-cipants provided written informed consent approvedby the Tel Aviv Sourasky Medical Center EthicsCommittee and the IDF Ethics Board.

PTSD and depression measurements

PTSD symptoms were evaluated with the militaryversion of the 17-item PTSD Checklist (PCL;Weathers et al. 1993), which specifically asks aboutsymptoms related to stressful military experiences.Depression symptoms were evaluated with the nine-item Patient Health Questionnaire (PHQ-9; Kroenke& Spitzer, 2002; Löwe et al. 2004; Fann et al. 2005).Three participants did not complete these question-naires, and thus were excluded from analyses concern-ing these variables.

Anxiety measurement

Trait anxiety was assessed using Spielberger’s Stait–Trait Anxiety Inventory, Trait Version (STAI-T;Spielberger et al. 1970; Barnes et al. 2002). To discriminatebetween high (mean = 37.8 ± 5.0, n = 28) and low traitanxiety (mean = 25.8 ± 3.4, n = 27), we used a mediansplit of STAI-T scores (which was 31 in our sample), asin prior studies (Mogg et al. 2008; Sheppes et al. 2013).Possibly because ofmilitary screening processes, anxietylevels of our high and low trait anxiety groups werelower than the common cut-off levels in non-clinicalpopulations (Eysenck & Byrne, 1992).

Threat bias assessment

Threat-related attention bias was evaluated using theDPT adapted to functional magnetic resonanceimaging (fMRI) with angry faces as the threat signal(Mogg & Bradley, 1999) using E-Prime version 1.0.Two face stimuli, one emotional (angry or happy)and one neutral, were shown briefly in each trial,and their offset was followed by a probe in the locationoccupied by just one of these faces. Each trial beganwith a 500-ms central fixation cross. Two faces thenappeared for 500 ms. These were replaced by a pairof dots in one hemifield for 1100 ms. The inter-trialinterval was between 1485 and 2300 ms (Fig. 1a). Forthe measure of threat bias, there were two conditionsof interest: (1) threat-congruent trials, in which anangry/neutral face pair was followed by a probe atthe location of the angry face; and (2) threat-incongru-ent trials, in which an angry/neutral face pair was

followed by a probe at the location of the neutralface. Threat bias scores reflect the difference betweenmean reaction times for threat incongruent versusthreat congruent trials. A bias score in the positiverange, which reflects faster mean reaction time to tar-gets appearing at the location of threat stimuli, wastermed vigilance. A bias score in the negative rangereflects the opposite pattern, which was termed threatavoidance.

Although threat trials were the main experimentalcondition of interest, three other control conditionswere included: happy-congruent and happy-incongru-ent trials following a happy/neutral face pair, and neu-tral trials following neutral/neutral face pairs. Therewere 24 trials for each of the four emotional conditionsand 48 trials for the neutral condition. In addition, 115blank trials (no faces and no pair of dots) were pre-sented. Trial presentation order was determined ran-domly for each participant. Equal numbers of trialsdisplayed the emotional face on right and left hemifi-elds. Participants were instructed to respond as quicklyas possible by pressing one button with their indexfinger if the dots were horizontal or a second buttonif the dots were vertical, thus leaving the emotionalcomponent implicit. Participants initially practicedthe task outside the scanner. This practice task in-cluded eight neutral trials.

Trials with incorrect response, trials in which the re-sponse time was 2 standard deviations below or abovethe participant’s mean for a particular condition, andtrials in which response time was faster than 150 mswere excluded from the analysis. Participants wereallocated to groups according to their threat bias direc-tion (in the negative or positive range): avoidance(n = 25) and vigilance (n = 30). A similar classificationhas been used in clinical samples (Price et al. 2011;Waters et al. 2012).

MRI data acquisition and analysis

Brain scanning was performed on a GE 3-T SignaHDxt MRI scanner (GE Healthcare, USA) with aneight-channel head coil. Functional images wereacquired using a single-shot echo-planar T2*-weightedsequence. The following parameters were used:repetition time/echo time (TR/TE) = 2400/35 ms, flipangle = 90°, field of view (FOV) = 20 × 20 cm, matrixsize = 96 × 96, 26 axial slices, slice thickness = 4 mm,and no gap covering the entire brain. Acquisitionorientation was of the fourth ventricle plane. In ad-dition, each functional scan was accompanied by athree-dimensional (3D) scan using a T1-spoiled gradi-ent recalled (SPGR) sequence (1 × 1 × 1 mm3). Datawere preprocessed and analyzed using conventionalstatistical parametric mapping (SPM5). fMRI data

Individual differences in resilience to chronic military stress 3

preprocessing included correction for head movement(subjects with movement >2 mm were discarded),realignment, normalizing the images to MontrealNeurological Institute (MNI) space and spatiallysmoothing the data [full-width at half-maximum(FWHM) = 6 mm]. The first four functional volumes,before signal stabilization, were excluded from theanalysis.

Statistical maps were prepared for each participantusing a general linear model (GLM), in which the

five task conditions were defined as district predictors:happy-congruent, happy-incongruent, angry-congru-ent, angry-incongruent and neutral. Time points fortrials in which participants responded incorrectly orwith reaction times outside of a predefined time win-dow were placed in a separate vector and includedin the regression model as a nuisance covariate.Following Monk et al. (2006), whole-brain individualstatistical parametric maps were calculated for thea priori defined contrast of interest of angry faces versus

(a)

(b)

Fig. 1. Threat bias, trait anxiety and post-traumatic stress disorder (PTSD) symptoms. (a) Sequence of events in the dot-probetask (DPT) of the three possible trials. Vigilance is represented by faster reaction to congruent trials (dark gray) versusincongruent trials (light gray), and avoidance is reflected by the opposite pattern of response. (b) Severity of symptoms withregard to trait anxiety level and threat bias group. ANOVA revealed a significant interaction showing that high anxiousindividuals with vigilance bias have increase PTSD symptoms compared to high anxious avoiders and to low anxietyindividuals (left graph), a pattern of results that was not obtained for depression symptoms (right graph). *p < 0.05.

4 T. Lin et al.

baseline. At group level, anatomical masks wereplaced in a priori defined regions of interest (ROIs) in-cluding the hippocampus, amygdala, ACC and lPFCand multiple comparisons corrections were performed(false-discovery rate, FDR < 0.05). Bilateral amygdala,hippocampus and ACC were defined according tothe Automated Anatomical Labeling (AAL) atlas(Tzourio-Mazoyer et al. 2002). The lPFC includedthe dorsolateral PFC [dlPFC; Brodmann area (BA) 9,10, 46] and the ventrolateral PFC (vlPFC; BA 44, 45)and was defined using the Talairach Daemon BAs(Lancaster et al. 2000). For each participant, β weightswere extracted and averaged across all voxels withineach ROI that exceeded the set threshold, and subse-quently averaged across angry congruent and angryincongruent conditions.

Mediation analysis

Mediation describes possible causal mechanisms ofcomplex processes by revealing intervening variablesthat may fully or partially account for the relationshipbetween two variables. An indirect path may alsoreveal an otherwise non-existent direct relationshipbetween these variables. Using the INDIRECT pro-cedure for SPSS (Preacher & Hayes, 2008), a standardthree-variable path model was used to obtain furtherinsight into the neural mechanism of threat bias andPTSD symptoms. The indirect effect was consideredto be significant if its 95% bootstrap confidence inter-vals (CIs) from 10 000 iterations did not include zeroat p = 0.05.

Results

Characteristics of threat bias groups

The mean attention bias was 25.4 ± 3.8 ms for thevigilance group and −24.7 ± 4.2 ms for the avoidancegroup, both scores significantly different from zero(t29 = 5.8, p < 0.001 and t24 =−7.21, p < 0.001 respect-ively). The means of both avoidance and vigilancegroups in our study are similar to those found in gen-eralized anxiety disorder and social phobia (Waterset al. 2012). Notably, the groups did not differ in biasscores for happy faces (F1,53 = 0.01, p = 0.99), indicatingthat the attention bias characteristics used for group as-signment are specific to threat-related stimuli. Threatbias groups did not differ in task accuracy (F1,53 =0.51, p = 0.48; vigilance group: mean = 94.3%, S.E. = 1.3;avoidance group: mean = 92.9%, S.E. = 1.1), indicatingthat general perceptual or motor phenomena did notcontribute to the observed attentional differences.

The effect of trait anxiety and threat bias on PTSDsymptoms

To test for the relationship between trait anxiety level,threat bias group and PTSD symptoms, a 2 × 2 analysisof variance (ANOVA) was conducted with trait anxiety(low, high) and bias group (avoidance, vigilance) asbetween-subject factors. Although no significant maineffects of trait anxiety (F1,48 = 3.04, p = 0.08) and biasgroup (F1,48 = 2.64, p = 0.11) were found, the interactionbetween these two variables was significant (F1,48 =4.90, p < 0.05; Fig. 1b). Post-hoc analyses revealed thathigh trait anxious vigilant individuals (mean = 29.13,S.E. = 1.98, n = 15) showed more PTSD symptoms thanhigh anxious avoidance individuals (mean = 20.91,S.E. = 2.31, n = 11; F1,48 = 7.28, p < 0.05). The differencebetween group means (8.22 points on the PCL scale)is considered a reliable difference (Monson et al.2008). In this analysis we also found that, among vig-ilant participants, high trait anxious individuals hadmore PTSD symptoms than low trait anxious indivi-duals (F1,48 = 8.86, p < 0.05). Taken together, it seemsthat shifting attention away from threat among hightrait anxious soldiers is related to more PTSDsymptoms.

To test whether the effect of trait anxiety and atten-tion bias is specific to anxiety-related symptoms, weperformed the same analysis for depression symptoms.This analysis revealed a significant main effect oftrait anxiety (F1,48 = 12.47, p < 0.05). However, therewas no main effect of bias group (F1,48 = 0.04, p = 0.84)and no interaction between trait anxiety and threatbias (F1,48 = 1.66, p = 0.20; Fig. 1b), suggesting that theobserved threat bias effect is specific to anxietysymptoms.

The effect of trait anxiety and threat bias on brainactivity

At the whole-group level we found increased acti-vation to angry faces versus baseline in the lefthippocampus (−33, −24, −15) and bilateral amygdala(−27, 3, −18; 27, 3, −18), along with decreased acti-vation in the dorsal ACC (dACC; −6, 42, 0) anddlPFC (−45, −33, −15) (Table 1 and Fig. 2). For eachof these regions, an ANOVA was performed withtrait anxiety and bias group as between-subject factors.For hippocampal activity we found a significanttwo-way interaction among trait anxiety and biasgroup (F1,51 = 5.41, p < 0.03) (Fig. 2a). Post-hoc analysisrevealed a significant difference in hippocampalactivation between avoidant and vigilant participantsin the high trait anxiety group (F1,51 = 6.79, p < 0.05)but not in the low trait anxiety group (F1,51 = 0.43,p = 0.29), with enhanced hippocampal activity inhigh anxious avoiders (mean = 0.34, S.E. = 0.08, n = 12)

Individual differences in resilience to chronic military stress 5

relative to high anxious vigilant individuals (mean =0.07, S.E. = 0.07, n = 15). There were no main effects oftrait anxiety (F1,51 = 0.01, p = 0.80) and bias group(F1,51 = 1.95, p = 0.33) on hippocampal activity. Similaranalyses for the activations of the amygdala (rightand left), ACC and dlPFC revealed no significantmain effects or interactions (all F’s < 2.7, p’s > 0.11;Fig. 2b–d). To confirm that the effect observed for thehippocampus is specific to threat (i.e. angry faces),we performed an equivalent analysis for hippocampalresponse to happy faces, in which no main effects orinteractions were found (all F’s < 1.4, p’s > 0.25).

Typifying the functional relationship betweenhippocampal activity, threat bias and PTSDsymptoms

Our ANOVA results indicate that high anxious avoi-ders show enhanced hippocampal activity and reportfewer PTSD symptoms compared with high anxiousvigilant individuals. Importantly, this effect was absentin low trait anxious individuals. This raises two possi-bilities of functional relationships between threat bias,hippocampal activity and PTSD symptoms amonghigh trait anxious individuals: (a) hippocampal activityhas an effect on PTSD symptoms through attentionalthreat bias; and (b) threat bias has an effect on PTSDsymptoms through engagement of the hippocampus.To test these options, we performed two separate me-diation analyses (Preacher & Hayes, 2008) among hightrait anxiety individuals (n = 26). This analysis depicteda significant indirect path from hippocampal activity toPTSD symptoms through threat bias in high anxiousindividuals (indirect effect = −12.07, 95% CI −29.69

to −2.90; Fig. 3a). Specifically, enhanced hippocampalactivity led to fewer PTSD symptoms through atten-tional threat avoidance. The alternative indirect pathin which threat bias could lead to decrease in PTSDsymptoms through enhanced hippocampal activitywas not significant (indirect effect = −0.02, 95% CI−0.98 to 0.05). Both indirect paths were not significantin low trait anxious individuals (threat bias indirect ef-fect = 0.05, 95% CI −1.4 to 2.23; hippocampal activityindirect effect = −0.02, 95% CI −0.02 to 0.008).

Testing for a regulatory role of the PFCin threat bias

To further elucidate the neural mechanism underlyingthreat bias, we examined whether the PFC has a regu-latory role in the hippocampus by two additionalmediation analyses that explicitly tested whether therelationship between activations in dACC or dlPFCand threat bias could be explained by values of acti-vation in the hippocampus. As the response of theseregions was unrelated to trait anxiety (Fig. 2c, d),these analyses were performed on all participants(n = 55). We found a significant indirect path fromthe dACC to threat bias through the hippocampus(indirect effect = 5.34, 95% CI −16.72 to −1.34;Fig. 3b), supporting the notion that the dACC acts onthe hippocampus to influence threat bias. Conversely,the indirect effect of dlPFC through the hippocampuswas not significant (indirect effect = 2.99, 95% CI−12.29 to 0.32).

Discussion

Using a population of soldiers undergoing intense andstressful military training, we were able to delineatethe relationship between trait anxiety level, attentionalthreat bias tendency, brain activity in stress-relatednodes and severity of PTSD symptoms. High traitanxious combat soldiers with attentional threat avoid-ance tendency exhibited enhanced hippocampal ac-tivity in response to threat cues in the DTP and fewerPTSD symptoms than high trait anxious individualswith a vigilance bias tendency. The functional relation-ship between these factors among high anxious indivi-duals was depicted by mediation analysis, revealingthat increased hippocampal activity led to lower levelsof PTSD through the tendency of avoidance. Of note,the regulatory effect of the dACC on the hippocampusin determining threat bias tendency was revealed by amediation analysis that was unrelated to trait anxietylevel. Specifically, less deactivation in the dACC ledto more hippocampal activity and greater avoidancethreat bias. By considering trait anxiety level, threatbias and brain activity of major stress circuit nodes,

Table 1. Regions showing significant difference between threatand baseline

MNI peak voxel

Hemisphere x y z t valuea

Angry > baselineHippocampus Left −33 −14 −15 4.72Amygdala Left −27 3 −18 5.31Amygdala Right 27 3 −18 4.93

Baseline > angrydACC Left −6 42 0 4.76dlPFC Left −48 36 18 3.94

dACC, Dorsal anterior cingulate cortex; dlPFC, dorsolat-eral prefrontal cortex; MNI Montreal Neurological Institute.

a Student’s t given by statistical parametric mapping(SPM) output. Regions are represented by coordinates of themost significant voxel.

6 T. Lin et al.

our results provide, for the first time, a possible neuro-behavioral model for PTSD symptom severity amongindividuals exposed to prolonged stressful life occur-rence (see the proposed model in Fig. 4).

Our results demonstrate that vigilance compared toavoidance tendency was associated with more severe

PTSD symptoms among high anxious but not lowanxious individuals. This effect seems to be specificto PTSD-related symptoms, and was not found for de-pression symptoms (Fig. 1b). These findings shed lighton how factors known to contribute to stress-relatedsymptoms interact with each other. Importantly, our

(a) (b)

(c) (d)

Fig. 2. Regional activation maps in response to angry faces versus baseline (with an anatomical mask) and the correspondingregion of interest (ROI) analysis with trait anxiety and bias group as between-group factors in the ANOVA. (a) Only thehippocampus showed significant interaction, indicating that high anxious individuals with avoidance bias had enhancedactivity compared to high anxious vigilant individuals This interaction and all main effects were not obtained for (b) boththe left and right amygdala, (c) the dorsal anterior cingulate cortex (dACC) and (d) the dorsolateral prefrontal cortex (dlPFC).*p < 0.05.

Individual differences in resilience to chronic military stress 7

results demonstrate the presence of the two threat biastendencies in individuals with low trait anxiety and inthose with high trait anxiety. This suggests that underchallenging stressful circumstances, such as intensemilitary training, attentional threat biases may assistall individuals to cope with stress and provide pro-tection from the development of psychopathology.Nevertheless, the finding that trait anxiety interactswith threat bias to affect PTSD symptom severity sug-gests that, in low anxious individuals, both threat

biases may be sufficient for adaptive coping with pro-longed stress. In high anxious individuals, however, ex-cessive allocation of attention towards threat may havemaladaptive consequences of increased PTSD symp-toms, whereas attention away from threat may have aprotective effect. Notably, this notion is consistentwith a previous prospective study showing that beforecombat deployment, soldiers who show threat vigil-ance are at greater risk for PTSD measured 1 yearlater during combat deployment (Wald et al. 2013).

(a) (b)

Fig. 3. Models of the relationship between brain activity, threat bias and post-traumatic stress disorder (PTSD) symptoms.(a) The illustrated mediation model for the group of high anxious individuals (n = 26) depicts a significant indirect path fromhippocampal activity to PTSD symptoms through attentional threat bias. Specifically, enhanced hippocampal activity led tofewer PTSD symptoms through attentional threat bias of avoidance. (b) The illustrated mediation model for all participants(n = 55) depicts a significant indirect path from dorsal anterior cingulate cortex (dACC) activity to threat bias throughhippocampal activity. Specifically, less deactivation of the dACC led to avoidance threat bias through increased hippocampalactivity whereas more deactivation of the dACC led to vigilance through decreased hippocampal activity. β values are shownnext to the arrows indicating each link in the analysis. This model was not significant using the dorsolateral prefrontal cortex(dlPFC). *p < 0.05, **p < 0.0005.

Fig. 4. A neurobehavioral model accounting for resilience to post-traumatic stress disorder (PTSD) symptoms. The modelpostulates that, under stressful environments, personality factors of anxiety level determine the state-related bias of threatprocessing through hippocampal activity and its interplay with the dorsal anterior cingulate cortex (dACC), thus affecting thedevelopment of PTSD symptoms. Specifically, high anxious individuals with increased hippocampal activity to threat havefewer PTSD symptoms through an adaptive tendency of allocating attention away from threat stimuli (i.e. avoidance bias).The role of the dACC in modulating the effects of the hippocampus is also suggested. Avoidance is modulated by lessdeactivation of the dACC (that in turn leads to enhanced hippocampal activity) whereas vigilance is gained through moredeactivation of the dACC, leading to reduced hippocampal activity. The broken arrows represent the speculation that, in lowanxious individuals, the tendency to allocate attention towards and also away from threat is adaptive, despite beingmodulated by either high or low hippocampal activity through interplay of the hippocampus with the dACC.

8 T. Lin et al.

Our brain imaging results suggest that the hippo-campus plays a role in trauma-related psychopath-ology and is also relevant to attentional threat biastendency. This supports the hypothesis that the hippo-campus is important for adaptive coping with chronicand potentially traumatic stress. This assertion corre-sponds with a recent study showing attenuated re-sponse of the hippocampus during the DPT inclinically anxious youth (Price et al. 2014). Notably, inour study the relationship between the hippocampus,threat bias and PTSD symptoms was revealed in a mili-tary population with low levels of anxiety and onlyminor (subclinical) PTSD symptoms. Although cautionis required in interpreting the current results, we tenta-tively suggest a protective role for increased hippo-campal activity in response to threat stimuli, possiblythrough induction of an avoidance attention bias. Asthe hippocampus has been shown to control beha-vioral inhibition by contextual threat monitoring andevaluation (Bach et al. 2014), it is possible that, duringthe DPT, the hippocampus encodes and evaluates thecontext as threatening, and when it is highly activatedan inhibitory behavior such as threat avoidancebias can be achieved. The relationship between thehippocampus and PTSD symptoms is supported byprospective imaging studies indicating more PTSDsymptoms following potentially traumatic military ex-posure among soldiers with reduced hippocampal vol-ume and with greater changes in hippocampal activityand connectivity (Admon et al. 2009, 2013a, b).Furthermore, hippocampal activity during the DPThas been associated with risk for stress-related psychi-atric disorders such as PTSD (Fani et al. 2013). In sum,these findings indicate that accounting for trait andstate elements is important for elucidating the relation-ship between hippocampal activity and stress-relatedsymptoms, but further prospective studies are requiredto disentangle the role of the hippocampus inthreat-related attention bias and in PTSD symptomdevelopment.

As perturbed activation patterns in the amygdala isa common finding in dot-probe imaging studies ofanxious individuals (Monk et al. 2006; Telzer et al.2008), it is surprising that we did not find that theDPT differentiated between trait anxiety and threatbias groups. Prior studies, however, have focused onbetween-group comparisons that categorized partici-pants based on their clinical profiles rather than taskperformance (i.e. threat bias). Hence, the previouslyobserved differences in the DPT may possibly rep-resent basic functional abnormalities in anxiety thatare unrelated to threat bias, such as hyper-responsivityof the amygdala to emotional stimuli per se.

Unexpectedly, the PFC nodes revealed in responseto threat stimuli (i.e. dACC and dlPFC) did not

differentiate between the groups as defined by theinteraction between trait anxiety and threat bias.However, considering their crucial roles in regulatinglimbic function, we further investigated their interplayby mediation analyses across all individuals. We foundthat regardless of individual levels of trait anxiety, lessdeactivation of the dACC led to enhanced hippocam-pal activity and hence to avoidance tendency on theDPT (Fig. 3b). Although not directly demonstratedhere, this result may suggest that the interplay betweenthe hippocampus and the dACC may also affect thepsychopathology (see a summary model scheme inFig. 4). Although our results may be sufficient to tenta-tively propose this model, verifying it requires furtherresearch on a more severe pathological populationwith a larger variance in anxiety and PTSD symptoms.

Considering the role of the dACC in emotion regu-lation (Etkin et al. 2011), the current results may indi-cate that efficient implicit emotion regulation involvesthe hippocampus and attains avoidance tendency,thus plausibly providing protection from traumaticstress vulnerability. The fact that this model wasobtained for all individuals suggests that the interplaybetween the hippocampus and the dACC is importantin determining the direction of threat bias regardless oftrait anxiety. However, it is important to note that,among individuals with high trait anxiety, enhancedhippocampal activity may be sufficient to induce pro-cessing of threat stimuli through avoidance threatbias and hence provide protection from the develop-ment of PTSD symptoms (Fig. 4). Although thedACC has been implicated in cognitive control pro-cesses including conflict monitoring (Kerns et al.2004; Egner & Hirsch, 2005), in our analysis this regionshowed deactivation in response to threat stimuli ofangry faces in the context of the attention conflicttask. This is consistent with previous reports regardingdeactivation of the dACC in response to affective faces(Duval et al. 2013). Notably, dACC deactivation duringnegative affect has been previously interpreted as in-terference of emotional states with cognitive proces-sing, resulting in a failure to cognitively control andregulate emotional behavior (Sterzer et al. 2005). Inline with these findings, more deactivation of thedACC, which may lead to vigilance, might reflect animpaired ability to control and regulate the responseto threat in a priori susceptible individuals with hightrait anxiety, thereby leading to a heightened propen-sity for anxiety symptoms. Low anxious individualswith vigilance tendency, by contrast, may have alterna-tive strategies for counteracting the attenuated dACCactivity and the disposition to anxiety, making themmore resilient to PTSD. This speculation is possiblein light of the greater number of PTSD symptomsamong high anxious vigilant individuals compared

Individual differences in resilience to chronic military stress 9

to low anxious vigilant individuals (Fig. 1b). However,further study is necessary to test this hypothesis di-rectly and understand the alternative mechanismsthat enable low anxious vigilant individuals tocounteract the attenuated dACC activity.

In contrast to our expectations, the dlPFC, a majornode in attention allocation, did not play a regulatoryrole in controlling the association between the hippo-campus and threat bias. The dlPFC, however, isthought to be involved in other aspects of cognitiveprocessing during the DPT (Telzer et al. 2008) beyondattentional bias, such as maintaining task-specific in-formation about rules and goals (MacDonald et al.2000), which may be less associated with the hippo-campus and threat bias relationships.

Our results have several clinical implications. Asconcluded in a recent PTSD review (Shvil et al. 2013),understanding how different behavioral and neuralPTSD markers influence each other may assist in estab-lishing an objective gold standard biomarker for PTSD.Indeed, these results point to the importance of con-sidering state-related processing tendencies such asthreat bias, in addition to trait manifestations of anxi-ety, when investigating stress- and trauma-relatedbrain markers. Furthermore, the results of the currentstudy suggest that, when using attention bias modifi-cation (ABM) training, it may be useful to considerneurobehavioral markers of treatment efficacy suchas the a priori trait anxiety level, threat bias and the hip-pocampus–dACC interplay pattern. Finally, the iden-tified neural mechanism informs the development ofnovel individually tailored treatments targeting the in-terplay between the dACC and the hippocampus.Thus, high anxious individuals with vigilance biascould undergo ABM or alternatively could be trainedto directly up-regulate their hippocampal response tothreat cues by neurofeedback procedures. Conversely,we could speculate that low anxious individualsshould not alter their attentional bias, but insteadmight need to learn how to switch from one strategyto another, depending on the context. As attentionalbias could be regarded as an emotion regulation pro-cess (Todd et al. 2012), this notion is supported by re-cent research proposing that the adaptiveness ofemotion regulation strategies depends on the contextin which they are used (Troy et al. 2013).

Although conducting this study on a particularpopulation of healthy combat soldiers has helped togain an insight into PTSD resilience, to fully validatethis emerging model future studies should examinethese ideas in other populations. As our study wasconducted on a highly selective population thatunderwent extensive mental and physical screeningsby the IDF to verify they were competent to servein a combat elite unit, generalizing the resilience

mechanisms to other populations requires furtherstudies. Specifically, some of the participants werecharacterized with a small threat bias, thus it wouldbe important to test these effects among individualswith extreme biases in studies using a larger samplesize of healthy subjects or populations prone to showexaggerated biases. Similarly, our sample consisted ofindividuals with only moderate levels of trait anxiety,and should also be tested in truly high anxious popu-lations including healthy individuals with high traitanxiety scores and clinical populations. This shouldbe tested first in PTSD patients and subsequently inother anxiety-related disorders. It is reasonable toassume that, for each type of anxiety disorder, an anal-ogous yet different model will be identified, basedon the core brain regions implicated in that specificpathology. Additionally, the current study focusedon military training stress; thus further studies arerequired to extend these findings to other types ofstressors including actual combat exposure. Finally,the lack of a systematic trauma history assessmentraises the possibility that the PTSD symptoms reportedin the current study reflect not only military trainingstress exposure effects but also prior traumatic eventsthat have not been fully documented. As prior traumahistory has been associated with altered psychophysio-logical responses to subsequent trauma (Delahanty &Nugent, 2006), testing the proposed model in prospec-tive studies that assess PTSD symptoms prior to andafter military training may resolve this issue.

In conclusion, the present study depicts a neurobe-havioral mechanism by which the hippocampus andthe dACC modulate attentional threat bias to influencePTSD symptom severity. This work combines previousbehavioral and neural findings into a single broadmodel. Although mediation analyses should be inter-preted with caution, this study provides empirical sup-port to the widespread notion that threat bias maycontribute causally to the development and mainten-ance of pathological response to stress (MacLeodet al. 1986; Mogg et al. 1993; Kaspi et al. 1995).Furthermore, our results advocate that future researchaimed at identifying PTSD-related brain markersshould take into account individual differences intrait anxiety level and threat bias tendencies.

Acknowledgments

This work was supported by a grant from theU.S. Department of Defense, award numberW81XWH-11-2-0008. We thank G. Gilam for assist-ance with the mediation analysis.

Declaration of Interest

None.

10 T. Lin et al.

References

Admon R, Leykin D, Lubin G, Engert V, Andrews J,Pruessner J, Hendler T (2013a). Stress-induced reduction inhippocampal volume and connectivity with theventromedial prefrontal cortex are related to maladaptiveresponses to stressful military service. Human BrainMapping 34, 2808–2816.

Admon R, Lubin G, Stern O, Rosenberg K, Sela L, Ben-AmiH, Hendler T (2009). Human vulnerability to stressdepends on amygdala’s predisposition and hippocampalplasticity. Proceedings of the National Academy of SciencesUSA 106, 14120–14125.

Admon R, Milad MR, Hendler T (2013b). A causal model ofpost-traumatic stress disorder: disentangling predisposedfrom acquired neural abnormalities. Trends in CognitiveSciences 17, 337–347.

Bach DR, Guitart-Masip M, Packard PA, Miró J, Falip M,Fuentemilla L, Dolan RJ (2014). Human hippocampusarbitrates approach-avoidance conflict. Current Biology 24,541–547.

Bar-Haim Y, Lamy D, Pergamin L, Bakermans-KranenburgMJ, van IJzendoorn MH (2007). Threat-related attentionalbias in anxious and nonanxious individuals: ameta-analytic study. Psychological Bulletin 133, 1–24.

Barnes LLB, Harp D, Jung WS (2002). Reliabilitygeneralization of scores on the Spielberger State-TraitAnxiety Inventory. Educational and PsychologicalMeasurement 62, 603–618.

Bernton E, Hoover D, Galloway R, Popp K (1995).Adaptation to chronic stress in military trainees. Annals ofthe New York Academy of Sciences 774, 217–231.

Bishop S, Duncan J, Brett M, Lawrence AD (2004). Prefrontalcortical function and anxiety: controlling attention tothreat-related stimuli. Nature Neuroscience 7, 184–188.

Bishop SJ (2007). Neurocognitive mechanisms of anxiety: anintegrative account. Trends in Cognitive Sciences 11, 307–316.

Bishop SJ (2008). Neural mechanisms underlying selectiveattention to threat. Annals of the New York Academy ofSciences 1129, 141–152.

Bishop SJ (2009). Trait anxiety and impoverished prefrontalcontrol of attention. Nature Neuroscience 12, 92–98.

Bradley BP, Mogg K, White J, Groom C, Bono J (1999).Attentional bias for emotional faces in generalized anxietydisorder. British Journal of Clinical Psychology 38, 267–278.

Day AL, Livingstone HA (2001). Chronic and acute stressorsamong military personnel: do coping styles buffer theirnegative impact on health? Journal of Occupational HealthPsychology 6, 348–360.

Dedovic K, D’Aguiar C, Pruessner JC (2009). What stressdoes to your brain: a review of neuroimaging studies.Canadian Journal of Psychiatry 54, 6–15.

Delahanty DL, Nugent NR (2006). Predicting PTSDprospectively based on prior trauma history and immediatebiological responses. Annals of the New York Academy ofSciences 1071, 27–40.

Duval ER, Hale LR, Liberzon I, Lepping R, Powell NJ,Filion DL, Savage CR (2013). Anterior cingulate cortexinvolvement in subclinical social anxiety. PsychiatryResearch: Neuroimaging 214, 459–461.

Egner T, Hirsch J (2005). The neural correlates and functionalintegration of cognitive control in a Stroop task. NeuroImage24, 539–547.

Etkin A, Egner T, Kalisch R (2011). Emotional processing inanterior cingulate and medial prefrontal cortex. Trends inCognitive Sciences 15, 85–93.

Etkin A, Klemenhagen KC, Dudman JT, Rogan MT, Hen R,Kandel ER, Hirsch J (2004). Individual differences in traitanxiety predict the response of the basolateral amygdalato unconsciously processed fearful faces. Neuron 44,1043–1055.

Eysenck MW, Byrne A (1992). Anxiety and susceptibility todistraction. Personality and Individual Differences 13, 793–798.

Fani N, Gutman D, Tone EB, Almli L, Mercer KB, Davis J,Glover E, Jovanovic T, Bradley B, Dinov ID, Zamanyan A,Toga AW, Binder EB, Ressler KJ (2013). FKBP5 andattention bias for threat: associations with hippocampalfunction and shape. Journal of the American MedicalAssociation Psychiatry 70, 392–400.

Fani N, Tone E, Phifer J, Norrholm S, Bradley B, Ressler K,Kamkwalala A, Jovanovic T (2012). Attention bias towardthreat is associated with exaggerated fear expression andimpaired extinction in PTSD. Psychological Medicine 42,533–543.

Fann JR, Bombardier CH, Dikmen S, Esselman P, WarmsCA, Pelzer E, Rau H, Temkin N (2005). Validity of thePatient Health Questionnaire-9 in assessing depressionfollowing traumatic brain injury. Journal of Head TraumaRehabilitation 20, 501–511.

Gomez-Merino D, Drogou C, Chennaoui M, Tiollier E,Mathieu J, Guezennec CY (2005). Effects of combinedstress during intense training on cellular immunity,hormones and respiratory infections.Neuroimmunomodulation 12, 164–172.

Kaspi SP, McNally RJ, Amir N (1995). Cognitive processingof emotional information in posttraumatic stress disorder.Cognitive Therapy and Research 19, 433–444.

Kerns JG, Cohen JD, MacDonald AW, Cho RY, Stenger VA,Carter CS (2004). Anterior cingulate conflict monitoringand adjustments in control. Science 303, 1023–1026.

Klumpp H, Ho SS, Taylor SF, Phan KL, Abelson JL,Liberzon I (2011). Trait anxiety modulates anteriorcingulate activation to threat interference. Depression andAnxiety 28, 194–201.

Kroenke K, Spitzer RL (2002). The PHQ-9: a new depressiondiagnostic and severity measure. Psychiatric Annals 32, 1–7.

Lancaster JL, Woldorff MG, Parsons LM, Liotti M,Freitas CS, Rainey L, Kochunov PV, Nickerson D,Mikiten SA, Fox PT (2000). Automated Talairach atlaslabels for functional brain mapping. Human Brain Mapping10, 120–131.

Ledoux JE, Muller J (1997). Emotional memory andpsychopathology. Philosophical Transactions of the RoyalSociety of London. Series B: Biological Sciences 352, 1719–1726.

Löwe B, Unützer J, Callahan CM, Perkins AJ, Kroenke K(2004). Monitoring depression treatment outcomes with thePatient Health Questionnaire-9. Medical Care 42, 1194–1201.

MacDonald AW, Cohen JD, Stenger VA, Carter CS (2000).Dissociating the role of the dorsolateral prefrontal and

Individual differences in resilience to chronic military stress 11

anterior cingulate cortex in cognitive control. Science 288,1835–1838.

MacLeod C, Mathews A (1988). Anxiety and the allocation ofattention to threat. Quarterly Journal of ExperimentalPsychology. A, Human Experimental Psychology 40, 653–670.

MacLeod C, Mathews A, Tata P (1986). Attentional bias inemotional disorders. Journal of Abnormal Psychology 95,15–20.

McFarlane AC (1990). Vulnerability to posttraumatic stressdisorder. In Posttraumatic Stress Disorder: Etiology,Phenomenology, and Treatment (ed. M. E. Wolf andA. D. Mosnaim), pp. 3–20. American PsychiatricAssociation: Arlington, VA.

Mogg K, Bradley BP (1999). Some methodological issues inassessing attentional biases for threatening faces inanxiety: a replication study using a modified version ofthe probe detection task. Behaviour Research and Therapy37, 595–604.

Mogg K, Bradley BP, Hallowell N (1994). Attentional bias tothreat: roles of trait anxiety, stressful events, and awareness.Quarterly Journal of Experimental Psychology. A, HumanExperimental Psychology 47, 841–864.

Mogg K, Bradley BP, Williams R, Mathews A (1993).Subliminal processing of emotional information in anxietyand depression. Journal of Abnormal Psychology 102, 304–311.

Mogg K, Holmes A, Garner M, Bradley BP (2008). Effects ofthreat cues on attentional shifting, disengagement andresponse slowing in anxious individuals. Behaviour Researchand Therapy 46, 656–667.

Mogg K, Mathews A, Bird C, Macgregor-Morris R (1990).Effects of stress and anxiety on the processing of threatstimuli. Journal of Personality and Social Psychology 59,1230–1237.

Monk CS, Nelson EE, McClure EB, Mogg K, Bradley BP,Leibenluft E, Blair RJ, Chen G, Charney DS, Ernst M,Pine DS (2006). Ventrolateral prefrontal cortex activationand attentional bias in response to angry faces inadolescents with generalized anxiety disorder. AmericanJournal of Psychiatry 163, 1091–1097.

Monson CM, Gradus JL, Young-Xu Y, Schnurr PP, Price JL,Schumm JA (2008). Change in posttraumatic stressdisorder symptoms: do clinicians and patients agree?Psychological Assessment 20, 131–138.

Morgan CA (2001). Symptoms of dissociation in humansexperiencing acute, uncontrollable stress: a prospectiveinvestigation. American Journal of Psychiatry 158,1239–1247.

Preacher KJ, Hayes AF (2008). Asymptotic and resamplingstrategies for assessing and comparing indirect effects inmultiple mediator models. Behavior Research Methods 40,879–891.

Price M, Tone EB, Anderson PL (2011). Vigilant and avoidantattention biases as predictors of response to cognitivebehavioral therapy for social phobia. Depression and Anxiety28, 349–353.

Price RB, Siegle GJ, Silk JS, Ladouceur CD, McFarland A,Dahl RE, Ryan ND (2014). Looking under the hood of thedot-probe task: an fMRI study in anxious youth. Depressionand Anxiety 31, 178–187.

Sanders MJ, Wiltgen BJ, Fanselow MS (2003). The place ofthe hippocampus in fear conditioning. European Journal ofPharmacology 463, 217–223.

Satpute AB, Mumford JA, Naliboff BD, Poldrack RA (2012).Human anterior and posterior hippocampus responddistinctly to state and trait anxiety. Emotion 12, 58–68.

Sheppes G, Luria R, Fukuda K, Gross JJ (2013). There’s moreto anxiety than meets the eye: isolating threat-relatedattentional engagement and disengagement biases. Emotion13, 520–528.

Shin LM, Bush G, Milad MR, Lasko NB, Brohawn KH,Hughes KC, Macklin ML, Gold AL, Karpf RD, Orr SP,Rauch SL, Pitman RK (2011). Exaggerated activation ofdorsal anterior cingulate cortex during cognitiveinterference: a monozygotic twin study of posttraumaticstress disorder. American Journal of Psychiatry 168, 979–985.

Shin LM, Rauch SL, Pitman RK (2006). Amygdala, medialprefrontal cortex, and hippocampal function in PTSD.Annals of the New York Academy of Sciences 1071, 67–79.

Shin LM, Whalen PJ, Pitman RK, Bush G, Macklin ML,Lasko NB, Orr SP, McInerney SC, Rauch SL (2001). AnfMRI study of anterior cingulate function in posttraumaticstress disorder. Biological Psychiatry 50, 932–942.

Shvil E, Rusch HL, Sullivan GM, Neria Y (2013). Neural,psychophysiological, and behavioral markers of fearprocessing in PTSD: a review of the literature. CurrentPsychiatry Reports 15, 1–10.

Spielberger CD, Gorsuch RL, Lushene RE, Vagg P, Jacobs G(1970). Manual for the State-Trait Anxiety Inventory.Consulting Psychologists Press: Palo Alto, CA.

Sterzer P, Stadler C, Krebs A, Kleinschmidt A, Poustka F(2005). Abnormal neural responses to emotional visualstimuli in adolescents with conduct disorder. BiologicalPsychiatry 57, 7–15.

Taylor MK, Sausen KP, Potterat EG, Mujica-Parodi LR, ReisJP, Markham AE, Padilla GA, Taylor DL (2007). Stressfulmilitary training: endocrine reactivity, performance, andpsychological impact. Aviation, Space, and EnvironmentalMedicine 78, 1143–1149.

Telzer EH, Mogg K, Bradley BP, Mai X, Ernst M, Pine DS,Monk CS (2008). Relationship between trait anxiety,prefrontal cortex, and attention bias to angry faces inchildren and adolescents. Biological Psychology 79, 216–222.

Todd RM, Cunningham WA, Anderson AK, Thompson E(2012). Affect-biased attention as emotion regulation. Trendsin Cognitive Sciences 16, 365–372.

Troy AS, Shallcross AJ, Mauss IB (2013). Aperson-by-situation approach to emotion regulationcognitive reappraisal can either help or hurt, depending onthe context. Psychological Science 24, 2505–2514.

Tzourio-Mazoyer N, Landeau B, Papathanassiou D, CrivelloF, Etard O, Delcroix N, Mazoyer B, Joliot M (2002).Automated anatomical labeling of activations in SPM usinga macroscopic anatomical parcellation of the MNI MRIsingle-subject brain. NeuroImage 15, 273–289.

Vollstädt-Klein S, Loeber S, Richter A, Kirsch M, Bach P,von der Goltz C, Hermann D, Mann K, Kiefer F (2012).Validating incentive salience with functional magneticresonance imaging: association between mesolimbic cue

12 T. Lin et al.

reactivity and attentional bias in alcohol-dependentpatients. Addiction Biology 17, 807–816.

Wald I, Degnan KA, Gorodetsky E, Charney DS,Fox NA, Fruchter E, Goldman D, Lubin G, Pine DS,Bar-Haim Y (2013). Attention to threats andcombat-related posttraumatic stress symptoms:prospective associations and moderation by the serotonintransporter gene. Journal of the American MedicalAssociation Psychiatry 70, 401–408.

Waters AM, Mogg K, Bradley BP (2012). Direction of threatattention bias predicts treatment outcome in anxiouschildren receiving cognitive-behavioural therapy. BehaviourResearch and Therapy 50, 428–434.

Weathers FW, Litz BT, Herman DS, Huska JA, Keane TM(1993). The PTSD Checklist (PCL): reliability, validity, anddiagnostic utility. Paper presented at the Annual Meeting ofthe International Society for Traumatic Stress Studies, SanAntonio, TX, October 1993.

Individual differences in resilience to chronic military stress 13