Neuropsychologia 46 (2008) 2364–2370

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Neuropsychologia

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An amygdala response to fearful faces with covered eyesc, Si

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Aziz U.R. Asghara,b,∗, Yi-Chieh Chiuc, Glyn HallamHayley Wrightc, Andrew W. Youngb,c

a Hull York Medical School & Department of Biological Sciences, University of Hull, HU6b York Neuroimaging Centre, The Biocentre, York Science Park, University of York, Heslinc Department of Psychology, University of York, YO10 5DD York, UK

a r t i c l e i n f o

Article history:Received 10 December 2007Received in revised form 6 March 2008Accepted 12 March 2008Available online 1 April 2008

Keywords:AmygdalaFunctional magnetic resonance imagingFacial expression

a b s t r a c t

Findings of amygdala respwidening is the only faciato fearful versus neutral smaximum sensitivity, a bwhich included peri-amygstimuli was found for whtherefore use informationfearful compared to neutr

1. Introduction

Responsiveness of the human amygdala to facial expressions

of fear has been found in neuropsychological (Adolphs, Tranel,Damasio, & Damasio, 1994; Calder et al., 1996) and functionalimaging studies (Breiter et al., 1996; Morris et al., 1996), and isnow considered a well-established finding (Adolphs, 2002; Calder,Lawrence, & Young, 2001). Prominent lines of research have inves-tigated the laterality, time-course and stability of the amygdala’sresponse to fearful faces (Barrett, Bliss-Moreau, Duncan, Rauch, &Wright, 2007; Breiter et al., 1996; Johnstone et al., 2005; Phillips etal., 2001), its interconnectivity with other cortical and subcorticalresponses (Morris et al., 1998; Williams et al., 2006), and its relationto conscious awareness (Barrett et al., 2007; Pessoa, Japee, Sturman,& Ungerleider, 2006; Phillips et al., 2004; Whalen et al., 1998).

Much less is known about the cues involved in the amygdala’sresponse to fear. Facial expressions involve patterns of musclemovements that lead to changes in feature shape that can oftenbe particularly easily seen in one part of the face (for example, thesmiling mouth for happiness), though they usually lead to identi-fiable changes across more than one of the internal (mobile) facialfeatures. In the case of fear, the changes in the eye region are suf-ficient in themselves to allow accurate recognition of the emotion,

∗ Corresponding author at: York Neuroimaging Centre, The Biocentre, York SciencePark, University of York, Heslington, York YO10 5DG, UK. Tel.: +44 1904 567941;fax: +44 1904 435356.

E-mail address: aziz.asghar@hyms.ac.uk (A.U.R. Asghar).

0028-3932/$ – see front matter © 2008 Elsevier Ltd. All rights reserved.doi:10.1016/j.neuropsychologia.2008.03.015

wei Liuc, Hannah Molec,

KYork YO10 5DG, UK

eness to the eye region of fearful faces raise the question of whether eyeinvolved. We used fMRI to investigate the differential amygdala responseli for faces, eyes, and for faces in which the eye region was masked. Foresign was used, with a region of interest (ROI) centred on the amygdala

r areas. Evidence of amygdala responsiveness to fear compared to neutralces, eye region only, and for faces with masked eyes. The amygdala canfacial regions other than the eyes, allowing it to respond differentially to

es even when the eye region is hidden.© 2008 Elsevier Ltd. All rights reserved.

but it can also be seen (though less accurately) from the mouth(Calder, Young, Keane, & Dean, 2000).

Recent studies involving functional brain imaging (Morris,deBonis, & Dolan, 2002; Whalen et al., 2004) and neuropsychol-ogy (Adolphs et al., 2005; Dadds et al., 2006) have underlined theimportance of the eye region to the amygdala’s responses to fearfulfaces. These findings raise the question of whether the amygdala,in effect, can only respond to a single cue (the characteristic eye

widening seen in fear faces).

Although the evidence cited clearly establishes the importantpoint that the amygdala makes effective use of the eye region, itdoes not rule out the possibility that it may be responsive to othercues. For three reasons, we thought it unlikely that a single-featurecue such as eye widening would be the only one involved. First,the amygdala is involved more generally in processing informa-tion from the eye region (Spezio, Huang, Castelli, & Adolphs, 2007).Second, the amygdala is also involved in evaluations such as trust-worthiness, which are unlikely to be based on a single facial cue(Engell, Haxby, & Todorov, 2007; Winston, Strange, O’Doherty, &Dolan, 2002). Third, it shows responsiveness to auditory as well asto purely facial expressions of fear, as has been demonstrated inneuropsychological (Scott et al., 1997; Sprengelmeyer et al., 1999)and functional imaging (Phillips et al., 1998) studies of humans,and from single-cell recording studies demonstrating multimodalneurones responsive to both facial and vocal fear in the monkeyamygdala (Kuraoka & Nakamura, 2007).

We therefore used functional brain imaging to investigate theextent to which amygdala responsiveness to facial expressions offear is dependent on information from the eye region. To do this,

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we used the standard contrast of amygdala responses to fearfuland neutral stimuli in fMRI, with a block design to maximise thelikelihood of detecting signal change in the region of the amyg-dala. The contrast between fearful and neutral stimuli was made tofaces (replicating the most widely used procedure for demonstrat-ing amygdala responsiveness to fear), to stimuli comprising onlythe eye regions of fearful and neutral faces (to replicate the find-ings of amygdala responsiveness to the eye region), and to stimulicomprising fearful and neutral faces in which the eye region wasmasked by a solid grey stripe of the same shade as the image back-ground. If the amygdala responds only to information from the eyeregion, then there will be no difference in blood flow between thefearful and neutral faces with masked eye region, but if the amyg-dala can use information from regions other than the eye regionthen there will be a difference in amygdala blood flow to fearfuland neutral stimuli even when the eye region is not visible.

2. Materials and methods

2.1. Participants

Sixteen healthy participants (eight male, eight female) with a mean age of 24years (S.D. = 3.3, range 21–33 years) were recruited to the study. All participantsprovided written informed consent prior to participation in the study. The study wasapproved and conducted in accordance with the guidelines of the Ethics and ScienceCommittees of the York NeuroImaging Centre, University of York. All participantshad normal or corrected-to-normal vision and were right-handed.

2.2. Stimuli

Pictures from the FEEST series (Young, Perrett, Calder, Sprengelmeyer, & Ekman,2002) were used to create experimental stimuli. These are computer-manipulatedimages of facial expressions from the Ekman and Friesen (1976) series, and havebeen the most widely used stimuli in previous studies. To ensure good recognis-ability of the fearful expressions, versions that were 25% computer caricatures ofthe Ekman prototypes were used. The computer caricaturing procedure involvedincreasing any differences between a prototype emotional expression (in this casefear) and the corresponding neutral expression; this has been shown to enhance therecognisability of emotional facial expressions (Calder, Rowland, et al., 2000; Calder,Young, Rowland, & Perrett, 1997).

Whole-face images of neutral and 25%-enhanced fear expressions for four male(EM, JJ, PE, WF) and six female (C, MF, MO, NR, PF, SW) models were chosen; theseare the full set of models available in FEEST. All images had cropped hairstyles andneutral grey backgrounds, to ensure that any differences between conditions were,as far as possible, a direct result of manipulating the factors of interest to the study.

Fearful and neutral examples of three types of face stimuli were created: (a)whole faces (images presented as they are in the FEEST series); (b) eye region only,consisting of an eye region strip extracted from each of the whole face images;(c) eye region masked, the complementary image to the eye region only condi-tion, containing all other facial information apart from the eye region strip in (b)(Fig. 1). All three types of face images were centred on a grey background of the same

size (338 × 434 pixels) to minimise differences in overall visual properties such asaverage brightness (see Fig. 1).

2.3. Experimental paradigm

The combination of two within-subject factors, face type (whole faces, eye regiononly, faces with eye region masked) and emotion (fear and neutral), formed sixexperimental conditions in three matched pairs: fearful whole faces and neutralwhole faces; fearful eye region only and neutral eye region only; fearful faces witheye region masked and neutral faces with eye region masked. These six conditionswere presented in a block design, with each block consisting entirely of trials withone of the six types of stimuli. Interleaved between the experimental blocks wererest periods of the same length, consisting of a fixation cross on a grey background.

Within each experimental block, each of the ten identities of faces was pre-sented at least once. The presentation time for each stimulus was 850 ms, with aninter-stimulus interval of 150 ms. Five repetitions of the six conditions were pre-sented during the experiment, making thirty experimental blocks in total. In orderto maintain and monitor attention levels throughout the experiment, participantswere instructed to perform a one-back recognition task during each block of trials.This entailed participants making a response every time an image (chosen randomlyfor each block) was exactly the same as the immediately preceding image. In addi-tion, as a further precaution to sustain attention and reduce predictability of thetask, the number of repeat images in each block was varied between one and twotrials. Participants made responses to the experimental task via pressing a buttonwith their right index finger.

logia 46 (2008) 2364–2370 2365

The purpose of the experimental task was therefore to ensure that participantsattended to all of the stimuli, but there was no explicit instruction that related inany way to their emotionality. This is in line with most previous studies of amygdalaresponsiveness to fear faces, which have also avoided explicit classification of theimages as fearful or otherwise since it has been established that the use of an explicittask can affect the overall pattern of results (Lange et al., 2003).

The order of presenting the stimuli was pseudo-randomised (a) within each con-dition block and, (b) across the six conditions. Pseudo-random (rather than random)orders were used because of the need to keep the small number of response trialsspread throughout each block, and therefore maintain and monitor participants’attention to the task. Different versions of the overall experiment were generatedto counterbalance any potential order effects of presentation of the experimentalconditions to participants.

2.4. MRI scanning

Scanning was performed with a 3 T MRI system (General Electric, Signa HDExcite) with an eight channel phased array head coil (GE Signa Excite 3.0T, High Res-olution Brain Array, MRI Devices Corp., Gainesville, FL). Axial images were acquiredfor functional and structural MRI scans. Foam inserts were used to minimise headmovement during scanning.

For fMRI scanning, echo-planar images were acquired using a T2* weightedgradient echo sequence with blood oxygen level-dependent (BOLD) con-trast (TR = 3 s, TE = 35 ms, flip-angle = 90◦ , acquisition matrix = 128 × 128, field ofview = 240 mm × 240 mm). Whole head volumes were acquired with 30 contiguousaxial slices, each with an in-plane resolution of 1.9 mm × 1.9 mm and a slice thick-ness of 4 mm. The slices were positioned for each participant to ensure optimalimaging of the temporal lobe regions, wherein the amygdala is situated.

T1-weighted images of participants were acquired to provide high-resolutionstructural images of the brain using an IR (Inversion Recovery) prepared 3D-FSPGR(Fast Spoiled Gradient Echo) pulse sequence (TR 7.5 s, TE 3 ms, flip angle 20◦ ,acquisition matrix 256 × 256, field of view 260 mm × 260 mm, in-plane resolution1 mm × 1 mm, slice thickness 1 mm). Localiser scans were used to align axial imagesalong the anterior commissure–posterior commissure line.

2.5. fMRI data analysis

Image analysis was carried out using FEAT (FMRI Expert Analysis Tool) Ver-sion 5.63, part of FSL (FMRIB’s Software Library, http://www.fmrib.ox.ac.uk/fsl).For each individual participant (first level analysis) the following pre-statisticsprocessing was applied; motion correction using MCFLIRT (Jenkinson, Bannister,Brady, & Smith, 2002), the mean displacements across the sixteen participantswere small and within acceptable limits, mean ± S.D. of the absolute displace-ment = 0.31 ± 0.15 mm, and relative displacement = 0.04 ± 0.01 mm (FSL, motioncorrection report); slice-timing correction using Fourier-space time-series phase-shifting; non-brain removal using BET (Smith, 2002); spatial smoothing usinga Gaussian kernel of full width half maximum of 6 mm; mean-based intensitynormalisation of all volumes by the same factor; highpass temporal filtering(Gaussian-weighted least-squares straight line fitting, with sigma = 50.0 s).

The haemodynamic BOLD response for each of the six experimental conditions(fearful whole faces, neutral whole faces, fearful eye region only, neutral eye regiononly, fearful masked eye region, neutral masked eye region) was modelled using asquare stimulus waveform convolved with a gamma haemodynamic response func-tion along with its temporal derivative. Time-series statistical analysis was carried

out using FILM (FMRIB’s Improved Linear Model) with local autocorrelation cor-rection (Woolrich, Ripley, Brady, & Smith, 2001). Registration of each participant’sfMRI images onto their high resolution T1 structural scan and then subsequently tothe Montreal Neurological Institute standard brain (MNI152) was carried out usingFLIRT (Jenkinson et al., 2002; Jenkinson & Smith, 2001).

For each participant, linear subtractions between parameter estimates wereused to determine the following three contrasts: fearful whole faces minus neu-tral whole faces; fearful eye region only minus neutral eye region only; fearful faceswith eye region masked minus neutral faces with eye region masked. These con-trasts allow identification of activations where the perception of fearful expressionsis greater than that for neutral expressions. In addition, such fearful minus neutralcontrasts within each stimulus type eliminate the effect of any overall visual differ-ences between whole faces, eye region only and eye region masked images to leaveonly the effects of “fearfulness” in the images. This then makes possible a compari-son between the three types of face-related stimuli despite differences in the levelsof visual information in the images.

2.6. Regions of interest and mixed effect analysis

Although the primary region of interests (ROI) in this investigation are theright and left amygdalae, it is apparent upon inspection of voxels in publishedstudies that activations to fear face conditions/contrasts not only occur within theamygdala itself but are also located in peri-amygdalar regions (Breiter et al., 1996;Calder et al., 2001; Hariri, Tessitore, Mattay, Fera, & Weinberger, 2002; Johnstoneet al., 2005; Knight, Nguyen, & Bandettini, 2005; Morris et al., 2002; Thomas etal., 2001; Whalen et al., 1998; Whalen et al., 2001). In the current investigation,

2366 A.U.R. Asghar et al. / Neuropsychologia 46 (2008) 2364–2370

le faceof ea

Fig. 1. Examples of neutral (upper row) and fearful (lower row) stimuli used. Whoonly and eye region masked stimuli were created by masking complementary parts

right and left cuboid-shaped amygdaloid ROIs were therefore constructed such thatthe amygdala and peri-amygdalar voxels were definitively included in the partici-pant group analysis. The right cuboid amygdaloid ROI comprised all voxels withinthe MNI152 coordinates x = 8–32 mm, y = −12 to 2 mm and z = −26 to −10 mm andthe left cuboid amygdaloid ROI, x = −6 to −30 mm, y = −12 to 2 mm and z = −26 to−10 mm.

Statistical analysis of group data (higher level analysis) was carried out by FLAME(FMRIB’s Local Analysis of Mixed Effects), part of FSL (Beckmann, Jenkinson, & Smith,2003; Woolrich, Behrens, Beckmann, Jenkinson, & Smith, 2004), using the right andleft amygdaloid ROIs. For the fear faces grouping, a mixed effect analysis was usedto produce Z (Gaussianised T/F) statistic images that were thresholded using GRF-theory-based maximum height thresholding with a corrected significance thresholdof p = 0.05 (Worsley, Evans, Marrett, & Neelin, 1992). For each of the contrasts: fearfaces minus neutral faces, fear eye region only minus neutral eye region only, andfear masked eye region minus neutral masked eye region, Z (Gaussianised T/F)statistic images were thresholded at p = 0.05 (uncorrected). An uncorrected anal-ysis was performed for these three contrasts for the following reasons: (1) To allowcomparison with other investigations which have utilised uncorrected analyses forcontrasts involving fear face-related stimuli and amgydala activation (Hariri et al.,2002; Johnstone et al., 2005; Morris et al., 2002; Whalen et al., 2004). (2) A mixedeffect analysis was selected, which takes into account both inter-subject and withinsession variability, providing a more stringent statistical analysis than for a fixedeffect analysis. (3) The fact that the ROI analysis encompassed voxels in the peri-amygdalar regions as well as the amygdala itself meant that a corrected analysis

images were taken from the FEEST series (Young et al., 2002), and the eye regionch image.

for multiple comparisons would be overly conservative, given the strong a prioriexpectation of amygdala responsiveness.

All Z statistical maps of the participant group mixed effect analysis were nor-malised onto the MNI152 standard brain template and all coordinates are given withrespect to this template (x, y, z, mm).

3. Results

3.1. Behavioural data

Table 1 shows the mean percentages of hits and false positiveresponses for each condition. The high hit rates and low false pos-itives in each of the six conditions indicate that participants wereable to sustain attention to stimuli across all conditions.

A repeated measures ANOVA was used to analyse hit ratesacross emotion (fear or neutral) and type of stimulus (whole face,eye region only, or face with eye region masked). Neither the maineffect of emotion (F(1,15) = 0.42, p > 0.1) nor the interaction betweenthe emotion and the type of stimulus (F(2,30) = 2.31, p > 0.1) wassignificant. There was a significant main effect of type of stimulus

A.U.R. Asghar et al. / Neuropsycho

Table 1Mean percentages of hits and false positive button presses to images in fear and neutral e

Fear-wholefaces

Neutral-wholefaces

Fear-eyeregion only

Neutral-eyeregion only

Fm

Hits 96.0 97.2 92.6 89.8 9False positives 0.9 1.3 2.3 0.5

(F(2,30) = 4.63, p < 0.05) in which the contrast between whole faceand eye region only conditions showed a significant difference(F(1,15) = 5.09, p < 0.05), with lower mean hits in the eye region onlycondition. The contrast between the whole face and the eye regionmasked conditions did not reach significance (F(1,15) = 0.41, p > 0.1).

A comparable repeated measures ANOVA of false positiveresponses did not reveal any significant effects, including the maineffect of type of stimulus (F(1,15) = 0.55, p > 0.1).

Fig. 2. Statistically significant maps depicting activations in response to fearful faces (corregions. The amygdaloid ROIs selected for the right and left sides are shown (shaded bStatistical images are superimposed onto the MNI152 standard brain (coronal, sagittal andat the lower right side of each panel in (A and B). The mean parameter estimates (arbitrarmaximum right amygdaloid voxel (x = 18, y = −8, z = −18), and (D) the maximum left amygneutral faces, FE: fearful eye region only, NE: neutral eye region only, FM: fearful faces wgiven in square brackets, (C and D), are the total number of significant voxels activated fo

logia 46 (2008) 2364–2370 2367

xperimental conditions

ear faces with eye regionasked

Neutral faces with eyeregion masked

Overall mean ± S.D.

3.8 97.7 94.5 ± 31.4 0.6 1.2 ± 0.6

3.2. Functional imaging

To analyse the fMRI data, a mixed effect analysis was first per-formed considering only the effect of fear faces in the right andleft amygdaloid ROIs. Fear faces resulted in significant activations(increases in BOLD signal) in the right and left amygdaloid regions,shown in Fig. 2 along with the parameter estimates. The coordinatesof the maximum voxel activated (corrected p-value of 0.05) in the

rected voxel thresholding, p-value of 0.05) in the (A) right, and (B) left amygdaloidoxes) in the coronal, saggital and axial planes (for details of ROIs see Section 2).axial planes) presented in radiological format with x, y or z coordinates (mm) giveny units ± S.E.M.) are graphically presented for all conditions with respect to (C) thedaloid voxel (x = −26, y = −6, z = −24), in the fear faces condition. FF: Fear faces, NF:ith eye region masked and NM: neutral faces with eye region masked. The values

r each condition (corrected voxel thresholding, p-value of 0.05).

2368 A.U.R. Asghar et al. / Neuropsychologia 46 (2008) 2364–2370

Fig. 3. (A) Sequential coronal sections (MNI152 standard brain coordinate from y = −12within voxels (uncorrected thresholding, p-value of 0.05) with the following contrasts: feregion only (FE − NE); fearful faces with eye region masked minus neutral faces with eyeside amygdaloid ROIs (see Fig. 2 and Section 2). Images are presented in radiological formThe mean parameter estimates (arbitrary units ± S.E.M.) are graphically presented for thFM − NM contrasts, along with the associated parameter estimates of the individual cond

right amygdaloid area was x = 18, y = −8, z = −18 (MNI152 standardbrain coordinates, mm) with a Z score = 3.8 and a % BOLD increaseof 0.16 ± 0.01; left amygdaloid area, x = −26, y = −6, z = −24 with a Zscore = 3.5 and a % BOLD signal increase of 0.15 ± 0.01. These acti-vations of the amgydaloid regions and the % BOLD increase withfear faces are similar to those reported previously (Morris et al.,2002).

Having confirmed that fear faces induce activation of the amyg-daloid region, a mixed effect analysis was next performed whichdetermined whether significant activations occurred with the con-trasts fearful faces minus neutral faces, fearful eye region only minusneutral eye region only, and fearful faces with eye region maskedminus neutral faces with eye region masked, using the right and leftamygdaloid ROIs (uncorrected voxel thresholding, p-value of 0.05).

to 2, each slice 4 mm thick) which depict statistically significant signal increasesarful faces minus neutral faces (FF − NF); fearful eye region only minus neutral eyeregion masked (FM − NM). Statistical images were masked using the right or leftat with the y coordinate (mm) given at the lower right side of each coronal slice.

e right and left amygdaloid ROI maximal voxel for (B) FF − NF, (C) FE − NE, and (D)itions.

Fig. 3 shows that the contrast fearful faces minus neutral facesproduced significantly activated voxels in the most anterior coro-nal slices (y = −2, 0 and 2) within the right amygdaloid ROI, andin the left amygdaloid activation in the two most posterior coro-nal slices (y = −12 and −10) and one coronal anterior (y = 2) slice(Fig. 3A). Both right and left amygdaloid activations in the samecoronal slice were only seen in the most anterior (y = 2) coronalslice (Fig. 3A).

The fearful eye region only minus neutral eye region only con-trast resulted in both right and left amygdaloid activations (y = −10and −8), and in the left side only in one coronal (y = −12) slice(Fig. 3).

The most striking finding was from the fearful faces with eyeregion masked minus neutral faces with eye region masked con-

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Table 2Coordinates of the maximal voxel activated for contrasts of fearful and neutral whoROIs

Right amygdaloid ROIFear faces minus neutral facesFear eye region only minus neutral eye region onlyFear faces with eye region masked minus neutral faces with eye region masked

Left amygdaloid ROIFear faces minus neutral facesFear eye region only minus neutral eye region onlyFear faces with eye region masked minus neutral faces with eye region masked

All activations are significant using uncorrected voxel thresholding with p = 0.05.

trast, where there was activation in the right and left amygdaloidregions spanning all coronal slices (y = −12 to 2) in the ROI (Fig. 3).Moreover, the voxels with the highest Z values were located towardsthe right posterior amygdaloid area (y = −12 to −6, Fig. 3).

Table 2 shows the maximum voxel activated (highest Z value)and the associated MNI152 brain coordinates in the right and leftamgydaloid ROI for each of the three contrasts (fearful faces minusneutral faces, fearful eye region only minus neutral eye region only,and fearful faces with eye region masked minus neutral faces witheye region masked). Fig. 3B and C shows a graphical representa-tion of the parameter estimates for the maximal voxel for each ofthese contrasts. All of the three contrasts showed activations in theright and the left amygdaloid areas. The voxel with the highest Zvalue overall was with the fearful faces with eye region maskedminus neutral faces with eye region masked contrast in the rightamygdaloid area (Z value of 3.8, MNI152 coordinates, x = 22, y = −12,z = −20 mm). The largest number of voxels activated in either theright or left amygdaloid regions was with the fearful faces with eyeregion masked minus neutral faces with eye region masked contrast(Table 2). There were approximately two-fold more activated voxelswith fearful faces with eye region masked minus neutral faces witheye region masked in the right amygdaloid area than the left. Thetotal number of voxels activated in the fearful faces minus neutralfaces contrast was approximately three-fold greater in the rightamygdaloid region than the left (Table 2). In contrast, fearful eyeregion only minus neutral eye region only had approximately eight-fold more active voxels in the left amygdaloid area than the right(Table 2).

4. Discussion

As expected, amygdala activation was found for the fearful facesminus neutral faces and for the fearful eye region only minus neutraleye region only contrasts, in line with findings already establishedin the literature on amygdala responsiveness to fear.

For present purposes, however, the critical contrast involvesfearful faces with eye region masked minus neutral faces with eyeregion masked, which allowed us to investigate whether the amyg-dala activation demonstrated for the fearful faces minus neutralfaces is simply due to the presence of the eye region in these stimuli.The eye region was completely obscured in the eye region maskedcondition, but there was a clear amygdala response to fear stim-uli containing none of the eye region. This shows that informationfrom the eye region is not essential to the amygdala’s response tofear. This does not, of course, imply that the eye region is not impor-tant; it just means that the amygdala does not rely on this regionexclusively.

An alternative way to think about our findings might be toconsider that for the fearful faces with eye region masked out, par-

logia 46 (2008) 2364–2370 2369

e, eye region only, and masked eye region stimuli in the right and left amygdaloid

NI152 brainordinates (mm)

Z value % BOLD increase Total number ofvoxels activated

y z

4 2 −18 2.3 0.16 ± 0.02 430 −8 −24 1.8 0.18 ± 0.02 22 −12 −20 3.8 0.18 ± 0.01 130

4 −12 −24 2.5 0.11 ± 0.01 146 −8 −24 2.8 0.29 ± 0.03 150 −10 −18 2.5 0.12 ± 0.01 69

ticipants recognise the fearful mouth and then somehow imaginethe equivalent eye region. Amygdala activation might then be aconsequence of trying to form a mental image of the missing fear-ful eye region. This would be interesting in its own right, but itis clearly a different interpretation from our suggestion that theamygdala can respond to cues from other facial regions. Any ten-dency to try to form a mental image of the covered region of theface would, of course, be enhanced by our choice of a block design,which inevitably makes the stimuli relatively predictable. The blockdesign was chosen to give the best opportunity to differentiateBOLD signals in the amygdala region, but confirmation of the pat-tern of findings using an event-related paradigm might be useful.At present, though, we think this interpretation in terms of cre-ating a mental image is unlikely because participants were notrequired to recognise the presence of fearful expressions. Althougha behavioural task was used during the scanning session, it was aone-back paradigm whose only purpose was to ensure that partici-pants attended to all of the stimuli. There was no explicit instructionthat related in any way to their emotionality.

A contentious issue has been the way in which visual infor-mation reaches the amygdala. Responses to signals of potentiallylife-threatening danger in the environment (such as facial expres-sions of fear) need to be made quickly, and it has been suggestedthat visual information can reach the amygdala via a fast, directpathway that bypasses visual cortex (Morris, DeGelder, Weiskrantz,& Dolan, 2001; Morris, Ohman, & Dolan, 1999). Findings of amyg-dala responsiveness to single cues (such as eye-widening in fearfaces) can be seen as consistent with this idea. However, the exis-

tence of this direct pathway has been disputed by Pessoa andUngerleider (2004), who point out that it is ‘unclear how a pro-posed subcortical pathway would support the processing of thedetailed form information needed for face perception’.

Limitations of the time-course of fMRI mean that it does notdirectly address the issue of a fast pathway to the amygdala, but ourfindings are indirectly relevant insofar as a separate pathway mighthave different properties to those found in ‘normal’, conscious per-ception of fear. This, though, is not what we found. Instead, ourobservations of amygdala responsiveness to a range of cues are con-sistent with data from psychological studies of perception of fear infaces. These have shown that despite the salience of the eye region,we typically combine information from different regions of the faceto make a holistic response when perceiving fear (Calder, Young, etal., 2000). For example, Calder, Rowland, et al. (2000) and Calder,Young, et al. (2000) showed that perception of fear in one part ofthe face (such as the top half, containing the critical eye region) isaffected by cues present in other parts of the face.

More generally, it seems that we do not perceive informationfrom the eye region in isolation from other aspects of the face. Theperception of eye gaze direction is affected by head orientation and

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other cues to social attention (Langton, Watt, & Bruce, 2000), andthe same set of eyes will appear bigger if combined with the mouthregion from a happy face compared to the mouth of a surprised face(Seyama & Nagayama, 2002).

The amygdala forms part of what Haxby, Hoffman, and Gobbini(2002) consider to be the ‘extended’ rather than the ‘core’ net-work of brain regions involved in face perception. By allocating itto the extended network Haxby et al. (2002) imply that the amyg-dala does not subserve a general function needed for a variety oftasks to do with faces, but has a more specialist role(s). It is richlyinterconnected not only with visual regions but with auditory andeven multimodal areas (Calder et al., 2001; Calder & Young, 2005;Kreifelts, Ethofer, Grodd, Erb, & Wildgruber, 2007), and is thereforewell-positioned to show responsiveness to a range of social cues, bethey from face, voice, posture or environmental context. However,logic is no substitute for fact, and despite the clear pointers fromits neurological connectivity it would have been perfectly possiblethat the amygdala might draw only on a single facial cue originatingin the eye region in responding to fearful expressions. Our findings,though, suggest otherwise. The amygdala can use information fromregions other than the eye region, allowing it to respond differen-tially to fearful compared to neutral faces even when their eyes arehidden.

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