NeuroImage 54 (2011) 3111–3116

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Evidence for a general face salience signal in human amygdala

Andreia Santos ⁎, Daniela Mier, Peter Kirsch, Andreas Meyer-LindenbergCentral Institute of Mental Health, J5, 68159 Mannheim, Germany

⁎ Corresponding author. Fax: +49 621 1703 2005.E-mail address: andreia.santos@zi-mannheim.de (A.

1053-8119/$ – see front matter © 2010 Elsevier Inc. Aldoi:10.1016/j.neuroimage.2010.11.024

a b s t r a c t

a r t i c l e i n f o

Article history:Received 2 June 2010Revised 18 October 2010Accepted 8 November 2010Available online 21 November 2010

Keywords:ThreatEmotionSalienceAmygdala

In the social neuroscience of face processing, multiple roles are attributed to amygdala: signalling of fear/threat-stimuli, of emotional expression, and general salience. The current study aimed at a direct comparison ofamygdala activation attributable to these conditions by contrasting amygdala responses to matched emotional(threatening and non-threatening) and of non-emotional salient faces in a visual search paradigm using cartoonfaces. Participants (21 healthy volunteers) had to detect a target face (angry, happy, blue, red, differing in theexact same features) in anarray of closelymatchednon-target faces. Behavioural results revealed a pop-out effectfor all targets compared to non-targets, indicating that theywere all salient, independently of being emotional ornon-emotional. While significant amygdala activation was obtained for all trials with salient faces (compared tothose containing only non-target faces), no significant differences in activation emerged between emotionalthreatening, emotional non-threatening, and non-emotional targets. Moreover, right and left amygdalaactivation for target trials was found correlated to the behavioural measure of target detection. These findingsprovide evidence for a general role of the amygdala in signalling salience in a visual search independent ofmodality. Given the critical involvement of the amygdala in several neuropsychiatric disorders, the currentfindings may contribute to further our understanding on dysfunctional neural circuits in these disorders.

Santos).

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© 2010 Elsevier Inc. All rights reserved.

Introduction

Detection of potential threats in the environment has clear adaptivevalue and humans are thought to be biologically prepared or “hard-wired” for the recognition of threat (Öhman, 1993). For instance,behavioural studies using classic visual search paradigms (e.g., “face-in-the-crowd”) have shown that angry faces, which are universally read aspotent warning signals for threat, are particularly effective in capturingattention, and are thus detected faster and more efficiently than non-threatening faces (Armony and Dolan, 2002; Öhman et al., 2001;Pourtois et al., 2004; Vuilleumier and Schwartz, 2001). This clearevolutionary advantage, allowing to anticipate danger, prepare defen-sive behaviour and hence to escape potentially dangerous situations(Öhman et al., 2001; Öhman andMineka, 2001), is thought to involve akey neural structure, the amygdala (LeDoux, 2000).

Classically, the amygdala has indeed been regarded as a threatdetector/fear module. This idea has received strong support fromanimal research (LeDoux, 2000; Prather et al., 2001), human brainimaging studies on fear conditioning (Büchel et al., 1998; Tabbertet al., 2005) and studies on neurological patients (Adolphs and Spezio,2006; Adolphs et al., 1995). Brain lesion studies, for instance, haveshown that bilateral amygdala damage impairs recognition ofthreatening stimuli and fear from static (Adolphs et al., 1995) and

dynamic (Graham et al., 2007) facial expressions. Similarly, inWilliams syndrome, reduced activation of amygdala to threateningfaces corresponds to clinically reduced social fear (Meyer-Lindenberget al., 2005; Muñoz et al., 2010).

Although there is little doubt that the amygdala is a criticalcomponent of the neural circuitrymediating conditioned fear responses(LeDoux, 2000; Öhman and Mineka, 2001), the notion that theamygdala has a specialized role in fear processing has been challengedby studies showing that the amygdala also responds to other negative,as well as positive emotional expressions (Fusar-Poli et al., 2009;Garavan et al., 2001). For instance, studies including fearful, disgusted,angry, sad, happy and neutral facial expressions have shown thatamygdala responses are not selective for any particular emotioncategory and can be observed for each facial expression separately(Fitzgerald et al., 2006). These results thus suggest that the amygdalamay have a more general-purpose function in signalling emotion infaces (Fitzgerald et al., 2006; Norris et al., 2004; Sergerie et al., 2008).Basedon the circumplexmodel of affect, emotions canbeunderstoodontwo independent dimensions, valence and arousal, subserved bydissociable neural systems (Gerber et al., 2008; Posner et al., 2005).Gerber et al. (2008) have shown that, when viewing facial expressions,amygdala activation correlates positively with ratings of absolutevalence and inversely with ratings of arousal. The authors interpretedthese findings as related to the salience of faces rated as having extremevalence and to the ambiguity of faces rated as having low arousal(Gerber et al., 2008), suggesting that both extreme valence and lowarousal lead to greater activation of an ambiguity/salience system

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subserved by the amygdala. According toWhalen (1998) and Davis andWhalen (2001) in ambiguous stimulus situations which need greatervigilance and arousal the amygdala is critically involved in modulatingsuch moment-to-moment levels of vigilance. To decide to approach oravoid an ambiguous stimulus, for instance, it is likely that the brainneeds to gather more information and that a system designed topromote vigilance and attention would show greater activation (Davisand Whalen, 2001). A number of studies have indeed shown that theamygdala responds to novelty or stimulus salience – e.g., unpredictablestimuli (Herry et al., 2007), novel images (Weierich et al., 2010),attractiveness (Winston et al., 2007), self-resemblance (Platek and Krill,2009), eye-gaze (Adams et al., 2003), novel faces (Schwartz et al., 2003;Todorov and Engell, 2008). Taken together, these findings indicate amore general function for the amygdala than in the classical view, andone suggested hypothesis is that the amygdala is an evolved system forrelevance detection, regardless of valence (Sander et al., 2003). Diversefindings from imaging, human lesion and animal studies support thishypothesis that the amygdala is specifically involved in the appraisal ofrelevant events that include, but are not limited to, fear-related stimuli.The fact that the amygdala is positioned at a critical nexus interactingboth with subcortical regions, including the brain stem and hippocam-pus, as well as several cortical areas including orbitofrontal andcingulate cortices (Amaral et al., 1992) makes amygdala an idealcandidate for a first stage relevance/salience detector. In line with thisidea, it has been shown that the amygdala is involved in the detection ofbehaviourally relevant simple visual non-emotional stimuli (Ousdal etal., 2008), as well as of social and emotional stimuli, indiscriminately,and independently of the stimulus modality (Scharpf et al., 2010).However, these previous studies included either non-emotional oremotional stimuli only,making it difficult todisentangle the specific roleof emotional content and salience in driving amygdala responses.

To clarify this issue, the current study investigated amygdalaactivation in processing salient threatening (angry) and non-threatening (happy) emotional faces, salient non-emotional (neu-tral-blue or neutral-red, see further details below) faces and non-salient faces. A visual search paradigm in which participants had todetect a target face in an array of non-target faces was used andparticipants’ behavioural and neural responses were compared intarget-present and target-absent trials. Based on Sander et al. (2003,pp. 311) assumption that an event is relevant (or salient) if it cansignificantly influence the attainment of the individual's goals, targetfaces were considered salient only if, compared to non-target faces,these significantly influenced participants’ search performance. Incontrast to previous experiments, this study examined the role ofamygdala in threat, emotional and general saliency processing in thesame individuals, using closely matched stimuli across all theconditions, and could confirm salience behaviourally through a“pop-out” effect, i.e., more efficient detection of target than non-target faces. If the amygdala is specifically involved in the signalling offear/threat-stimuli, then increased amygdala activation should beobserved for angry relative to happy and non-emotional target faces.If the amygdala is rather responsible for signalling emotional faces,then both angry and happy target faces should elicit increasedamygdala responses compared to non-emotional targets. Finally, if theamygdala has a more general role in detecting salient stimuli,independently of these being threatening or emotional, thenincreased amygdala activation should be found for all targetsindiscriminately relative to non-targets faces.

Materials and methods

Participants

This study included 21 healthy volunteers (11 female) aged 21–36 years (M=27.2; SD=3.5). All participants were right-handed. Atthe time of testing, they were all free of medication, had normal or

corrected-to-normal vision and had no overt physical handicap, orknown psychiatric/neurological disorders. Written informed consentwas obtained for all participants and the study was approved by thelocal ethics committee.

Stimuli and procedure

Stimuli comprised cartoon faces (same identity), consisting ofcoloured line drawings, displayed in 3×3 matrices (800×600 pixelssize at the screen) against a white background (Santos et al., 2010)Cartoon rather than real faces were used to avoid problems inequating real faces for confounding visual features such as shadows(Purcell et al., 1996).

We have used a visual search task, in which participants had todetect the presence/absence of one target (“intruder”) face sur-rounded by no-target (“crowd,” all equal) faces. Participants werepresented with a total of 144 trials. Half of the trials comprised onetarget face surrounded by 8 non-target crowd faces and the other halfcomprised 9 non-target crowd faces (no target). The target couldoccur at any of the 9 positions in the matrix. The position of the targetface was randomly assigned across trials and subjects. Target faceswere either emotional (36 trials, 18 angry, 18 happy) or non-emotional (36 trials, 18 with blue mouth and eyebrows, 18 with redmouth and eyebrows) faces. The same identity was used for all faces(emotional and non-emotional target faces, as well as crowd faces). Inall conditions, the differences between the target and the crowd faceswere limited to the eyebrows and the mouths (see Fig. 1).

Each stimuluswas presented for 2500 ms. Trials were separated bya black fixation cross on the center of a white screen. Inter-trialduration was jittered with a mean of 2000 ms (1000–3000 ms). Theorder of the trials presentation was pseudorandomized so that notmore than two trials of the same condition appeared consecutively.The experiment was implemented using Presentation software,version 9.50 (Neurobehavioral Systems, Albany, CA). Pictures wereback-projected onto a translucent screen and were viewed byparticipants through a mirror affixed at the head coil. Participantswere asked to decide, by pressing one of two keys on a response box, if“yes” or “no” (two-forced choice paradigm) there was an intruder facein the crowd. Participants were asked to respond as quickly andaccurately as possible. No feedback was given.

Apparatus and image acquisition

MRI data were collected using a 3T (Siemens Trio). After aligningthe images in a transversal plane parallel to the AC-PC-line on basis ofa localizer scan, a T1-weighted anatomical volume (TR=2300 ms,TE=3.03 ms, flip angle=9°, FoV=256 mm, matrix=256×256,voxel size=1 mm) was recorded.

Functional imageswere acquiredwith a T2*-weighted gradient echoplanar imaging sequence (TR=2000ms; TE=30ms; flip angle=80º;FoV=192 mm; matrix=64×64). Twenty-eight transversal slices perscan were collected in a descending order with a slice-thickness of4 mm+1mmgap(voxel size=3×3×5 mm).A total of 336 scanswerecollected during the experiment.

Image processing and data analyses

Preprocessing and statistical analyses were conducted usingStatistical Parametric Mapping software (SPM8, Welcome Departmentof Imaging Neuroscience, London, UK). Preprocessing included spatialrealignment, slice timing, normalization into the MNI space andsmoothing (FWHM 8mm). To control for low-frequency components,a high-pass filter with a cut off of 256 s was used. Statistical analyseswere performed using the general linear model as implemented inSPM8. A first-level fixed effects analysis using a general linear modelwith a regressor for eachcondition, consisting of a stick function for each

Fig. 1. Top (from left to right): Angry, happy, blue, red target faces, and non-target faces. Bottom: Example of the stimuli used in each condition.

Table 1Percentage of correct responses and RTs for correct responses for each condition.

Target No target

Emotional Non-emotional

Angry Happy Blue Red

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trial convolvedwith a hemodynamic response function, was conductedfor each subject. To minimize the influence of movement relatedvariance, the six movement parameters of the realignment procedurewere included as covariates of no interest. The obtained contrasts ofinterest were as follows: targetNno target; emotional targetNnon-emotional target; angryNno target; happyNno target; blueNno target;redNno target. These contrastswere used for group analyses in a secondlevel random effects model, using one-sample t-tests. Region of interest(ROI) analyses were conducted for the amygdala with the Wake ForestUniversity Pick-Atlas (http://www.fmri.wfubmc.edu/cms/software).Significance threshold was set to pb .05 family-wise error (FWE)corrected for all analyses. In addition, to explore the relationshipbetween amygdala activation and behavioural performance the meanactivation of the peak voxel in the group analyses in the left and rightamygdala was extracted for the single contrasts, angry, happy, blue, redand no-target. Further analyses were conducted outside the SPMframework using Statistica 7 software (Statsoft). Data were analysedseparately for left and right amygdala usingone-wayANOVAs, includingcondition (angry, happy, blue, red, and no-target) as within-subjectsfactor. Post-hoc analyses were computed using Tukey HSD tests.Correlation analyses were computed using Pearson r tests. For eachsubject in each condition, percentage of correct responses1 and meanreaction times for correct responses (RTs) were computed.

Results

Behavioural results

Mean percentage of correct responses and mean RTs for correctresponses and standard deviations for each condition are presented inTable 1. Mean correct responses for all the conditionswere found above87%, possibly reflecting a ceiling effect. For this reason, only results fromanalyses on RTs are reported here. Mean RTs for each subject in eachcondition were first analysed using a one-way ANOVA including Target(present vs. absent) as within-subjects factor. Results revealed thatparticipants were faster (F (1,20)=354.37, pb .001) at responding totarget-present (M=1028, SD=179) than target-absent (M=1647,SD=256) trials. Further analyses (one-way ANOVA) on RTs includingCondition as a within-subjects factor revealed a significant main effect(F (4,80)=130.15, pb .001). Post-hoc analyses using Tukey testsrevealed that all the target faces, angry, happy, blue and red weredetected faster than non-targets (all psb .001), indicating that all thetargets were salient.

In order to investigate differences between emotional and non-emotional targets, analyses were conducted separately for target-present trials, using a two-way ANOVA including Target (Emotional,Non-emotional) and Condition (Angry-Happy, Blue-Red) as within-

1 Percentage rather than total scores were computed for each condition given thedifferent number of trials in the target and the non-target conditions.

subjects factors. Results of analyses on RTs revealed a significant maineffect of Target (F (1,20)=28.38, pb .001): participants were faster atdetecting non-emotional (M=946; SD=595 ms) than emotional(M=1110; SD=593 ms) targets. Importantly, a significant Target ×Condition interaction (F (1,20)=13.04, p=.002) was also found.Results of post-hoc analyses using Tukey tests revealed that while theemotional angry and happy conditions significantly differed betweeneach other (pb .001), with participants being faster detecting angry(M=1026, SD=211 ms) thanhappy targets (M=1194, SD=185 ms),no such difference was found between the non-emotional blue(M=940, SD=170 ms) and red (M=952, SD=243 ms) conditions(pN .97). Moreover, no significant differences were found betweenangry and blue (p=.05), and angry and red (pN .10) targets, whereasRTs for happy targets were longer than that for blue (pb .001) and red(pb .001).

Functional imaging results

Target-present trials elicited stronger activation than non-targettrials in the inferior parietal lobule, as well as in the supramarginal,parahippocampal, inferior and middle frontal gyrus, the precuneusand the left amygdala (see Table 2 and Fig. 2).

ROI analysis on the amygdala revealed stronger activation inbilateral amygdala in target vs. non-target trials (Left: MNI coordinates:−18−2−22; T=6.98, p=b .001, k=118; Right: MNI coordinates: 22−4 −24, T=5.43, pb .001, k=97). In order to investigate amygdalaactivation in each condition,wehave also conductedROI analyses on thecontrast targetNno-target for each condition separately. Interestingly,stronger bilateral amygdala activation was found for all targets relativeto non-target trials, except for the angry targets, which elicited strongeractivation than non-target trials in the left amygdala only (see Table 3).Results of ANOVAs revealed a significant main effect of Condition onboth right (F (4,80)=8.22, pb .001) and left (F (4,80)=8.01, pb .001)amygdala activation. Post-hoc comparisons have shown that all thetarget conditions elicited higher responses in the right (Mangry=.46,SD= .62, p=.07; Mhappy= .94, SD= .67, pb .001; Mblue= .71,SD=.64, p=.003; Mred=.92, SD=.58, pb .001) and the left amygdala(Mangry=1.28, SD=.60, p=.004; Mhappy=1.41, SD=.59, pb .001;Mblue=1.46, SD=.59, pb .001; Mred=1.58, SD=.58, pb .001) than

Correct (%) 96.0 (6.6) 87.3 (12.6) 96.3 (5.6) 94.7 (13.2) 98.0 (3.6)RTs (ms) 1026 (211) 1194 (185) 940 (170) 952 (243) 1650 (256)

Table 2Brain activation for the contrast targetNno-target.

Main effect (targetNno target) BA L/R Cluster MNI T-value

Area x y z

Inferior parietal lobule 40 L 429 −50 −44 46 10.37Postcentral gyrus(somatosensory cx)

2 L −64 −30 40 7.41

Supramarginal gyrus 40 L −62 −52 36 7.13Parahippocampal gyrus 36 L 51 −34 −30 −22 10.15Parahippocampal gyrus 36 R 102 36 −26 −24 9.64Precuneus 39 R 364 44 −72 36 9.44

Middle temporal gyrus 39 R 54 −72 22 7.70Superior temporal gyrus 22 R 50 −56 20 7.36

Inferior parietal lobule 40 R 264 44 −54 42 9.10Supramarginal gyrus 40 R 56 −48 30 8.50Supramarginal gyrus 40 R 48 −48 36 8.14

Inferior parietal lobule 40 L 85 −40 −62 40 8.82Middle temporal gyrus 21 L 41 −62 −56 −2 8.28Middle frontal gyrus 47 R 14 52 42 −2 8.13Middle temporal gyrus 22 R 67 60 −48 2 8.02Postcentral gyrus(somatosensory cx)

2 R 39 64 −32 44 7.86

Middle frontal gyrus 8 R 19 34 22 50 7.66Inferior prefrontal gyrus 47 L 16 −22 10 −22 7.43Inferior frontal gyrus 45 L 13 −50 38 6 7.15Inferior parietal lobule 40 R 6 50 −44 54 7.00Amygdala L 5 −18 −2 −22 6.98

Table 3Amygdala activation for each contrast targetNno-target.

Trial Contrast Side MNI T-score p-valueFWE-corr

K

Emotional Angry N

no-targetL −18 −2 −22 5.17 .001 50R — — — —

Happy N

no-targetL −26 −2 −26 5.43 b.001 89R 24 −6 −22 4.84 .001 86

Non-emotional Blue N

no-targetL −20 −4 −22 6.50 b.001 91R 20 −2 −26 5.06 .001 89

Red N

no-targetL −20 −6 −20 6.90 b.001 104R 20 −6 −22 5.78 b.001 82

3114 A. Santos et al. / NeuroImage 54 (2011) 3111–3116

no-targets (Mno-target-right=−.10, SD=.67; Mno-target-left=−.42,SD=.58).

Whole-brain analyses revealed significantly increased activationto the emotional compared to the non-emotional targets in the visualcortex (middle occipital gyrus/inferior temporal gyrus of the occipitallobe, left: MNI coordinates: −40 −78 2; T=7.06, k=8, right: MNIcoordinates: 46 −66 −8; T=7.47, k=48). ROI analyses on theamygdala also failed to reveal differences between emotional andnon-emotional targets. When looking for non-significant differencesbetween emotional and non-emotional targets in the amygdala, themaximal T-value detected was 1.33 (puncorrected=.09) reflecting themarginal differences between both conditions in the amygdala. Powercalculation revealed that based on the corresponding effect size ofthat difference, at least 80 participants would have been needed todetect a potential difference by means of a ROI analyses.

Whole-brain analyses, as well as ROI analyses on the amygdala,revealed no significant differences in BOLD-responses between angry

Fig. 2. Brain activation for the contrast targetNno-target. Note: All voxels displayed aresignificant at a threshold of pb .05 FWE-corrected for the entire volume.

and any of the other target contrasts (happy, blue or red). Voxel-wiseanalyses also failed to reveal any significant differences.

Correlation analyses

To investigate whether the observed general salience signal inamygdala has behavioural relevance, we correlated the advantage inspeed processing (RTs), the quantification of behavioural salience,with the increase of amygdala activation (contrasts weight for eachsubject at the voxel where the strongest effect of the condition wasobserved for the whole sample) in target relative to non-target trials.Results revealed a significant and a marginally significant positivecorrelation between RTs and right (r=.42, p=.05) and left (r=.40,p=.07) amygdala, respectively. Exploratory whole-brain analyses didnot reveal additional, unhypothesized regions correlated with ourbehavioural measure of salience that survivedwhole-brain correction.

Discussion

This study aimed at investigating the role of the amygdala inprocessing threatening, emotional and salient face stimuli. Bypresenting emotional and non-emotional target faces on the back-ground of non-target control faces, we tried to investigate whetherthe amygdala specifically responds to the emotional content of thestimuli (LeDoux, 2000) or to the general change of salience leading toan increase of attention and vigilance independent of the emotionalcontext (Davis and Whalen, 2001).

Findings of this study indicate that rather than responding tothreatening or emotional stimuli specifically, the amygdala provides ageneral signal for behaviourally salient face stimuli, supporting thehypothesis of amoregeneral role of the amygdala in relevancedetection(Sander et al., 2003) ormodulation of attention and vigilance (Davis andWhalen, 2001), while providing no evidence indicating differentiallygreater responses related to threat (LeDoux, 2000) and emotiondetection (Fitzgerald et al., 2006; Norris et al., 2004; Sergerie et al.,2008), using closely matched stimuli in the same individuals.

Visual search paradigms like that used here mimic everydaysituations in which one attempts to find a target among other, non-target, stimuli. When asked to detect a target face in a crowd of non-target faces participants were found to respond faster in target-presentthan in target-absent trials, in agreement with previous studies(Frischen et al., 2008). If a particular target has a special salience, itspresence will be readily detected, even surrounded by numerousdistracters. By contrast, targets that do not possess such quality requireadditional cognitive resources, because the subject will need to processall items until the target is located. In this study, all the targets weredetected faster than the non-targets, indicating that they were allsalient, independently of being emotional or non-emotional. Thissaliency effect was more prominent for non-emotional than emotionaltargets (significantmain effect of Target). A possible explanation for thisresult could be a generally increased complexity of the emotionalcompared to the coloured pictures or a faster detection of local colour

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features over expression changes in eyebrow and mouth. However nodifferences in reaction timebetweenblue and red targetswere found. Inaddition, angry faceswere not only detected faster than happy faces butalso as fast as colour faces (significant interaction Target × Condition),arguing against overall differences in stimulus complexity or detect-ability. This conclusion is also supported by the design of facial stimuliused in our visual search task, which were carefully selected so thatemotional expressions could be readily recognized from simpleeyebrow and mouth line drawings (Magnussen et al., 1994) andrespected the criteria typically use to define a face as angry (V-shapedeyebrows and a narrow, down-curved mouth), happy (inverted V-shaped eyebrows and a upward-curvedmouth) and neutral (Lundqvistet al., 1999, 2004). Using these cartoon stimuli, differences in thedetection of angry and happy face targets are unlikely to be due to lowlevel visual confounds that can be present in real faces (Purcell et al.,1996). The finding that angry faces are detected more efficiently thanhappy faces in a crowd of distractor faces is evidence for an angersuperiority effect, commonly reported in healthy controls (Eastwoodet al., 2001; Fox et al., 2000; Gerritsen et al., 2008; Horstmann andBauland, 2006) and thought to depend on an evolved fear module withthe amygdala as a central structure (Öhman and Mineka, 2001). Thiseffect might be related to the fact that happy faces are commonlyperceived as safe, whereas angry faces are rather perceived as warningsignals of potential social danger (Öhman et al., 2001; Öhman andMineka, 2001), thus requiring faster responses.

At the neural level, it is broadly agreed that visual search iscontrolled through a fronto-parietal attentional network that inter-acts with and regulates processing in earlier (occipital) regions(Corbetta and Shulman, 2002). In agreement, our findings haveshown greater activation in frontal and inferior parietal areas/temporo-parietal junction (TPJ) in target-present than target-absenttrials (see Fig. 2). In particular, the TPJ appears to act as a ‘circuitbreaker,’ signalling the occurrence of unexpected but task-relevantstimuli in the environment where attention needs to be switched to,distinct from other sections of the fronto-parietal network controllingtop-down attention (Corbetta and Shulman, 2002). Furthermore, theright TPJ responds to stimulus saliency (Mavritsaki et al., 2010),playing a key role in guiding subsequent actions to that location.Visual search requires an interaction between bottom-up processesresponding to local feature differences between visual elements, andtop-down processes that set excitatory expectations for targets aswell as inhibiting irrelevant distractors (Treisman and Kanwisher,1998). Both excitatory guidance of search to targets and rejection ofirrelevant distractors are thus required (Humphreys et al., 2009).Separate networks of areas in parietal and occipital cortex have beenlinked to the top-down prioritisation of target features and the activesuppression of distractors (Mavritsaki et al., 2010). These networks, inacting together, facilitate visual search.

Furthermore, similar neural structures were found involved insearch for emotional and non-emotional targets. Only bilateralregions of the visual cortex (BA19) were found to respond strongerto emotional than to non-emotional targets. Increased visualactivation to emotional stimuli has been consistently reported (Langet al., 1998; Mourão-Miranda et al., 2003; Phan et al., 2002). Thereforethis increased activation can be interpreted as reflecting emotion-dependent processing given evidence that at the neural level regionscan be identified that respond specifically to the emotional content ofour target stimuli. However, in contrast with the behavioural results,at the neural level no angry superiority effect was found. Furthermore,as mentioned before, with respect to the amygdala, we found that notonly emotional (angry or happy) stimuli recruit this structure, butrather that the amygdala also responds to basic colour changes onfaces. Interestingly, stronger bilateral amygdala activation was foundfor all targets relative to non-target trials, except for the angry targets,which elicited stronger activation than non-target trials in the leftamygdala only. In line, lateralised left amygdala responses have also

been found in response to threat vs. safe conditions (Phelps et al.,2001). According to a previous study, lateralisation differences inamygdala activation may occur depending on whether the subjects areaware or not of the aversive nature of the stimuli, with left amygdalaresponding when subjects are aware and right amygdala respondingwhen subjects are unaware of this contingency (Morris et al., 1998).

Alternatively, one could argue that these findings suggest that theamygdala might respond to faces (Vuilleumier and Pourtois, 2007) ingeneral, independently of these being salient or not, given that all thetrials, target and non-target, included faces. The task goal may also havecontributed to our findings: in this visual search experiment, it mighthave been that the neural signal representing the search goaloverwhelmed differential activity between emotional or non-emotionalintruders. In a follow-up experiment, a task that focused more on thetype of emotion—for example, one that rates the level or typeof emotionin the face or one that requires the participants to specifically search forangry or colour intruders, might show a stronger emotion-specificeffect. It is nevertheless important to note that ourfindings are based onthe contrast between target vs. no-target faces which permits abehavioural readout of salience in a visual search through the reactiontime advantage (pop-out). Using thismeasure,we have found a positivecorrelation between amygdala activation and RTs, indicating theinvolvement of amygdala signalling in faster detection of targetsrelative to non-targets, a behavioural indicator of salience.

One plausible interpretation for the absence of differential BOLDresponse in the amygdala during the detection of emotional and non-emotional intruders is that, in the context of a visual search task, non-emotional target faces, compared to non-target faces, representedbiologically relevant stimuli for the participants, and reliablyproduced amygdala activation, as emotional faces did. This interpre-tation is in line with the idea that stimuli that require the brain togather more information and attentional resources activate theamygdala, a structure especially sensitive to the uncertainty ofstimulus contingencies (Holland and Gallagher, 1999; Whalen,1998). Accordingly, if amygdala plays a role in modulating levels ofvigilance in response to other than solely negative or emotional facestimuli, it is likely that the amygdala served this same function whendetecting non-emotional salient targets.

Taken together, the current findings provide evidence for a generalrole of the amygdala in signalling salience in faces independent ofthese being threatening, emotional or non-emotional. These findingsthus suggest that, at least in the visual search paradigm we studied,the amygdala plays a role in more general salience processing relatedto the behavioural relevance of the target stimulus, supersedingspecifically emotional signalling. We hope that the findings of thecurrent study contribute to further our understanding on the role ofthe human amygdala, as well as on its dysfunctions, which arecritically involved in a wide range of neuropsychiatric disorders.

Acknowledgments

We are grateful to all participants. Andreia Santos was supportedby the Fyssen foundation (France) to conduct this study. Datareported from this study were presented as a poster at the 16th

Annual Meeting of OHBM 2010 (Barcelona, Spain).

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