The Journal of Neuroscience, June 19, 2013 • 33(25):10483–10489 • 10483

Behavioral/Cognitive

Amygdala Activation for Eye Contact Despite Complete
Cortical Blindness
Nicolas Burra,2,3 Alexis Hervais-Adelman,3,4 Dirk Kerzel,2,3 Marco Tamietto,5,7 Beatrice de Gelder,5,6
and Alan J. Pegna1,2,3
1

Laboratory of Experimental, Neuropsychology Unit/Neurology Clinic, Department of Clinical Neuroscience and Dermatology, Geneva University Hospital,
CH-1211 Geneva, Switzerland, 2Faculty of Psychology and Educational Science, University of Geneva, CH-1211 Geneva, Switzerland, 3Neuroscience Center,
University of Geneva, CH- 1211 Geneva, Switzerland, 4Brain and Language Laboratory, University of Geneva Medical School, University of Geneva,
CH- 1211 Geneva, Switzerland, 5Cognitive and Affective Neurosciences Laboratory, Tilburg University, 5000 AB Tilburg, The Netherlands, 6Athinoula A.
Martinos Center for Biomedical Imaging, Massachusetts General Hospital-Harvard Medical School, Charlestown, Massachusetts 02129, and
7Department of Psychology, University of Torino, 10126 Torino, Italy

Cortical blindness refers to the loss of vision that occurs after destruction of the primary visual cortex. Although there is no sensory cortex
and hence no conscious vision, some cortically blind patients show amygdala activation in response to facial or bodily expressions of
emotion. Here we investigated whether direction of gaze could also be processed in the absence of any functional visual cortex. A
well-known patient with bilateral destruction of his visual cortex and subsequent cortical blindness was investigated in an fMRI paradigm
during which blocks of faces were presented either with their gaze directed toward or away from the viewer. Increased right amygdala
activation was found in response to directed compared with averted gaze. Activity in this region was further found to be functionally
connected to a larger network associated with face and gaze processing. The present study demonstrates that, in human subjects, the
amygdala response to eye contact does not require an intact primary visual cortex.

Introduction
It has long been known that a loss of occipital striate cortex leads
to blindness of cortical origin (e.g., Holmes, 1918). Although
such lesions obviously deprive a person of any conscious visual
sensation, evidence has accumulated showing that a substantial
amount of visual processing still remains possible without awareness. This residual capacity has been termed “blindsight” (Weiskrantz et al., 1974) and has been observed in a number of different
tasks, such as motion detection, target localization, or pointing
(Weiskrantz, 1986).
If evidence of blindsight was found for what could perhaps be
described as basic visual characteristics, subsequent observations
showed that more complex, emotional stimuli also produced
nonconscious processing. Indeed, de Gelder et al. (1999) discovered that emotional faces were processed even when they were
presented to a patient’s blind field and thus could not induce any
conscious percept, thereby demonstrating the existence of an “affective” blindsight. Subsequently, another patient (T.N.), who is
Received Aug. 21, 2012; revised May 15, 2013; accepted May 21, 2013.
Author contributions: N.B., D.K., B.d.G., and A.J.P. designed research; N.B., A.H.-A., M.T., B.d.G., and A.J.P.
performed research; N.B., A.H.-A., M.T., B.d.G., and A.J.P. analyzed data; N.B., A.H.-A., D.K., M.T., B.d.G., and A.J.P.
wrote the paper.
This work was supported by the Swiss National Science Foundation for Scientific Research Grants 320030 –
144187 and PDFMP1_129459.
The authors declare no competing financial interests.
Correspondence should be addressed to Dr. Alan J. Pegna, Laboratory of Experimental Neuropsychology, Neuropsychology Unit/Neurology Clinic, Geneva University Hospital, 4 Gabrielle-Perret-Gentil, CH-1211 Geneva 4, Switzerland. E-mail: alan.pegna@hcuge.ch.
DOI:10.1523/JNEUROSCI.3994-12.2013
Copyright © 2013 the authors 0270-6474/13/3310483-07$15.00/0

the subject of the current report, also proved to be able to guess,
with a success rate significantly above chance, whether a positive
or negative facial expression was presented to him (Pegna et al.,
2005). fMRI revealed that this was possible through activity of his
right amygdala, even though V1 was completely destroyed in this
person.
The fact that emotional stimuli can be processed without V1 and
without awareness is in line with the assumption that elements important for our survival, in particular threatening stimuli, may be
processed through a coarse and rapid subcortical pathway (LeDoux,
1998) to the amygdala. However, it seems unlikely that this pathway
would only process emotional expressions because other facial cues
are equally behaviorally relevant and could be necessary for the rapid
and automatic appraisal of a situation.
One stimulus of high significance in humans is the direction
of gaze. Indeed, direction of gaze provides important indications
regarding another person’s intentions and thus yields essential
information about avoidance or approach behavior. We hypothesized that, as for emotional faces, gaze may be processed in the
absence of awareness, bypassing primary sensory areas and accessing relevant brain structures through alternate channels. Furthermore, previous studies have shown that emotional facial
expressions activate the amygdala when high spatial frequencies
are filtered out, although this does not hold for stimuli removed
of their low spatial frequencies (Vuilleumier et al., 2003). This
was taken as evidence that the amygdala processes mainly the low
spatial frequency of the stimuli.
Consequently, using an fMRI block-design paradigm, we investigated the cerebral response to gaze in Patient T.N., who pres-

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Burra et al. • Amygdala Activation for Eye Contact

ents complete cortical blindness resulting
from bilateral loss of his visual cortex.
Photographs of faces, with high, low, or
no spatial frequency filtering, were presented with their gaze oriented toward or
away from him with the aim of determining
whether structures, such as the amygdala,
would respond to eye contact despite the patient’s inability to report the presence of any
visual stimulation. In addition, a group of
healthy controls matched for education, sex,
and age also performed the task for comparison purposes.

Materials and Methods
Case reports
Patient T.N. is a 57-year-old man trained and
still working as a physician. He suffered two
consecutive strokes at the age of 52, the first
in the left parieto-temporo-occipital cerebral
area, which initially produced right hemianopia, hemiplegia, and transcortical sensory
aphasia, which receded rapidly except for the
hemianopia. A second hemorrhage occurred in the right occipital lobe
producing a loss of the remaining (left) visual field.
Structural MRI shows that the lesion in the left hemisphere includes
most of the occipital lobe, with minimal sparing of the medial ventral
part of the inferior occipital gyrus and anterior part of the lingual gyrus.
The lesion extends anteriorly to the middle part of the fusiform gyrus
leaving the parahippocampal gyrus grossly intact. Laterally, the lesion
extends to the medial inferior temporal gyrus. Dorsally, the hemorrhage
reaches the superior parietal lobule and spares the ventral part of the
precuneus. The right hemisphere lesion is smaller and includes most of
the occipital lobe, with limited sparing of the medial part of the posterior
lingual gyrus and medial part of precuneus. The anterior border stretches
to the middle part of the fusiform gyrus and included the posterior inferior temporal gyrus but spares the parahippocampal gyrus. No anatomic
input to striate areas could be detected in either left or right hemisphere
using DTI.
Stimuli. Six different identities (3 male, 3 female) were created using
FaceGen Modeler 3.4, a software that has been already used in previously
published experiments on gaze perception (see, e.g., Ethofer et al., 2011).
Using ImageJ and a procedure suggested by other authors (Delplanque et
al., 2007), these avatars were desaturated and equalized for their facial
luminance (Fig. 1). Presented on a gray background, each picture, 512 ⫻
512 pixels, was then filtered using the parameters usedin a previous paradigm (Vuilleumier et al., 2003). This yielded three filtering conditions:
normal (unfiltered) pictures, low-pass filtered pictures (6 cycles/image),
and high-pass filtered pictures (32 cycles/ image). Using FaceGen settings
for the gaze deviation (50% of the maximal deviation), we deviated the
averted gaze positions in 50% of the presentations to the left and 50% to
the right. For the behavioral experiment, a pure tone at 440 Hz was
generated using Audacity 1.2.6.
Behavioral procedure. The stimuli were presented on a computer
screen situated at a viewing distance of 85 cm (outside the MRI scanner).
Half of the stimuli showed a face with an averted gaze (AG), and half
depicted a face with its gaze directed at the viewer (DG). Stimuli were
presented in a random order, and Patient T.N. was asked to press one of
two keys to respond whether the gaze was directed at him or not. Responses were cued by a brief tone (440 Hz, 50 ms) indicating the beginning of stimulus presentation. Patient T.N. was asked to respond after the
onset of the auditory cue. The next trial was initiated 1100 ms after the
response. Because of the absence of any effect shown by the patient in
guessing, the experiment was run twice more, during a brief testing session 2 years later. In the second of these two later tests, we emphasized the
importance of giving a rapid and intuitive response and insisted that he

Figure 1. Example of stimuli used in this study.
not make any effort but respond with spontaneity to his “gut feeling,”
instruction that proved fruitful.
fMRI procedure. Patient T.N., lying in the MRI scanner, was requested to simply keep his eyes open during the experimental presentation. Stimuli were projected onto a screen situated at the end of the
bore closest to the patient’s head. A mirror placed on the head coil
reflected the images from the screen directly toward the center of the
patient’s orbit. After verifying the position of the display mirror (before inserting Patient T.N. into the bore of the scanner), we monitored his gaze direction scrupulously during the recording session
with an eye tracker camera, although we were unable to calibrate the
eye tracker because of the impossibility for him to fixate calibration
points.
We presented 24 blocks of stimuli, each lasting 24 s. Blocks contained
6 tokens of a single condition presented for 2 s each (direct, averted,
direct low spatial frequency, averted low spatial frequency, direct high
spatial frequency, averted high spatial frequency) and were presented in a
pseudo-random order. Each of the six blocks was separated by a 26 s rest
period with no stimulation. Four blocks of each condition were presented, and each single picture was presented four times per block.
MRI data acquisition. Scanning took place in a 3T Siemens Trio MRI
scanner, using a 12-channel head-coil; 340 functional volumes were acquired in one single session, lasting ⬃12 min (T2*-weighted EPI, 32
sequential 3 mm slices, 15% interslice gap, 2.56 ⫻ 2.56 mm in-plane
resolution, angled away from the eyes to prevent ghost artifacts from
aliasing of eye movements; TA, 2 s; TR, 2 s; TE, 30 ms). A high-resolution
(0.43 mm ⫻ 0.43 mm ⫻ 1 mm voxels) T1-weighted anatomical image
was also acquired.
fMRI preprocessing and analysis. Analysis was performed using the
SPM 8 software package (http://www.fil.ion.ucl.ac.uk/spm/), with the
following steps: (1) realignment, in which EPI volumes were realigned
using a two-pass procedure (images were initially realigned to the first
volume, and a mean image was generated, to which the EPI volumes were
then realigned); (2) coregistration of the structural volume to the mean
EPI image; and then (3) spatial smoothing using a Gaussian kernel of 8
mm at full-width half-maximum height.
To be able to compare the patient’s neuroanatomy with that of existing
atlases, we normalized the T1 anatomical image to the standard MNI template included in SPM8, using the “unified segment” procedure, which is
robust in the face of lesions (Ashburner and Friston, 2005; Crinion, 2007).
The normalization parameters generated by this process were subsequently
applied to the contrast images produced by the functional analysis. Activation coordinates are reported in MNI space, and region identification was
determined using the SPM Anatomy Toolbox (Eickhoff et al., 2005).

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J. Neurosci., June 19, 2013 • 33(25):10483–10489 • 10485

by gaze direction. A PPI is defined as a
stimulus-dependent or context-dependent
change in the influence of one brain region on
another. A spherical ROI with radius 4 mm was
created, centered on the voxel showing the
maximum contrast in response to direct versus
averted gaze and the eigenvariate of the entire
BOLD signal time course corrected for effects
of interest was extracted.

Control group
Ten right-handed, age-matched, male participants (57 ⫾ 4 years of age) served as controls
for Patient T.N. None reported any neurological or psychiatric disorders. Participants were
naive as to the purpose of the experiment. The
local ethics committee had approved the study,
and informed consent was obtained from participants before the experiment.
fMRI data acquisition, preprocessing, and
analysis. Data acquisition and procedures for
controls were identical to those for Patient
T.N. fMRI data were preprocessed as for
Patient T.N., with an additional spatial normalization step performed before analysis.
Individual participants’ datasets were then
analyzed using a fixed effects model exactly
as for Patient T.N. Contrast estimates for the
effects of gaze direction and frequency were
calculated. A one-sample t test was then performed on the contrast images obtained from
all the subjects for each contrast of interest,
treating subjects as a random factor.
Results for the control group are presented
at an uncorrected level of p ⬍ 0.001, uncorrected for multiple comparisons, and a cluster
extent threshold of 10 voxels.

Results
Patient T.N.
Behavior
Patient T.N. was unaware of any of the
Figure 2. BOLD response in Patient T.N. when presented with photographs of direct gaze (DG) versus averted gaze (AG). a, A
stimuli presented to him and, in a behavsignificant activation was found in Patient T.N.’s right amygdala when blocks of faces with DGs were contrasted with photographs
of faces with AGs. Using a fixed model, voxels showing a significantly greater response ( p(FWE) ⬍ 0.05) for DG when contrasted ioral task performed outside the scanner,
with AG were displayed on Patient T.N.’s T1 structural scan. A significantly increased response (z-score ⫽ 5.02, p(FWE) corrected ⫽ failed to respond above chance when
0.004) was found in the right amygdala (MNI coordinates, 24; ⫺12; ⫺10; volume, 67 mm 3), consistent with previous findings asked to guess whether the gaze were
regarding gaze processing in normally sighted individuals (Kawashima et al., 1999) and affective blindsight in this patient (Pegna averted or directed at him (49% correct
et al., 2005). b, ␤ values representing activation in the right amygdala (MNI coordinates, 24; ⫺12; ⫺10) for nonfiltered (normal), responses for gaze contact; p ⫽ not sighigh-pass filtered and low-pass filtered images, showing no differences in-between conditions. The values illustrated here were nificant on a binomial distribution). As
obtained from the most significant voxel in the DG versus AG contrast and were not used for statistical computation. c, Contrast noted above, this was the result of the
estimates were significant for DG versus AG (bars indicate 90% confidence intervals).
patient’s difficulty accepting to guess.
Subsequently, a second testing session
yielded a similar result (48% correct reNonetheless, it is important to note that all figures, ␤ values, and
sponses,
p
⫽
not
significant).
However in the final session,
functional connectivity analyses that we report were performed on the
after having insisted on the necessity of relying on subjective
data in Patient T.N.’s native space.
impressions, Patient T.N.’s hit rate rose slightly to 57% which,
We used a general linear model in which every scan was coded for
condition. The BOLD response to each stimulus was modeled using the
although not highly significant, appears less random than durcanonical hemodynamic response function, along with its temporal and
ing the previous sessions ( p ⫽ 0.063 on a cumulative binomial
dispersion derivatives. Six movement parameters (x, y, and z translations
distribution).
and x, y, and z rotations) derived from the realignment step described
above were included in the model. A high-pass filter (cutoff 128 s) and
AR1 correction for serial autocorrelation were applied.
As there was no significant main effect of spatial frequency ( p(FWE) ⬎
0.05) on brain activity, we collapsed the data across all spatial filtering
conditions, leaving a single factor: gaze direction.
PPI of the right amygdala. A psychophysiological interaction (PPI)
(Friston et al., 1997) analysis was performed to determine regions showing functional connectivity with the right amygdala that was modulated

fMRI
fMRI results revealed that the right lateral amygdala produced a
larger response for DG than AG ( p(FWE) ⬍ 0.05; Fig. 2), whereas
no effect was found on spatial filtering. To more closely examine
the response of the amygdala as a function of spatial filtering, we
performed an additional ROI analysis focused on the amygdalae
(discussed below).

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10486 • J. Neurosci., June 19, 2013 • 33(25):10483–10489

Figure 3. PPI of right amygdala activation with locus ceruleus and right lingual gyrus activation. A, Seed region. B, Network of regions whose connectivity with the right amygdala was
significantly greater in DG than AG ( p(FWE) ⬍ 0.05, cluster extent threshold k ⬎ 10). Scatter plots below show the relative activity, trial by trial, in the amygdala and two regions: (i) locus ceruleus
(bottom left), which has previously been shown to respond to subliminal threatening stimuli) (Liddell et al., 2005) and (ii) the right lingual gyrus (bottom right), for DG (red) and AG (blue).

Based on this result, we investigated the functional connectivity of the right amygdala using a PPI technique (Friston et al.,
1997). This assessment revealed that, during the presentation of
DG versus AG, a significant coactivation of the amygdala was
found with several brain areas related to face and gaze processing
( p(FWE) ⬍ 0.05), including the right lingual gyrus and the right
temporal pole, the insula, the hippocampus, and the locus ceruleus (Fig. 3; Table 1).
Control group
Contrasting activation elicited by DG with that elicited by AG
revealed that the right lateral amygdala also exhibits a larger response to DG than AG (Fig. 4; Table 2). In addition, left amygdala
and hippocampus as well as the right fusiform gyrus were more
activated by gaze contact. No significant main effect of filtering
was observed, nor was there a significant interaction between
gaze direction and spatial frequency.
ROI analysis: amygdalae
An ROI analysis was performed using the Marsbar toolbox (Marseille ROI toolbox for SPM8). ROIs were created based on an
anatomical mask (WFU_PickAtlas toolbox) (Maldjian et al.,
2003) for each of the left and the right amygdalae. We then analyzed the data using these masks, which were determined independently of our functional data.
We obtained a clear difference between the DG and AG in the
right amygdala for Patient T.N. (t(305) ⫽ 2.70 p ⬍ 0.05) and the

control group (t(9) ⫽ 2.23, p ⬍ 0.05). At the single-subject level,
the effect DG ⬎ AG was significant (at p ⬍ 0.05) in two participants and marginally significant in another. In a further five participants, there was a nonsignificant trend for the effect in this
direction. In the remaining three participants, the effect was either null ( p ⬇ 1) or showed a nonsignificant trend in the opposite
direction.
No difference in activation for DG versus AG was found in the
left amygdala for Patient T.N. However, a significant effect of
gaze direction was present in the left amygdala for the control
group (t(9) ⫽ 3.43, p ⬍ 0.01). At the single-subject level, this effect
was significant (at p ⬍ 0.05) in three participants, marginally
significant in another, and with a nonsignificant trend in five
more. The remaining participant showed a nonsignificant trend
for the opposite effect.
We also investigated the effect of spatial frequency on
amygdala responses to gaze direction. There was no significant
main effect of spatial frequency in the amygdalae in either Patient
T.N. or the control group. No significant gaze direction by spatial
frequency interaction was found either in the left or right
amygdala of Patient T.N. or the control group,

Discussion
Our study shows that, although Patient T.N. lacks a responsive
primary visual cortex and has no subjective visual experience of
the stimuli presented to him, his right amygdala, in particular the

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J. Neurosci., June 19, 2013 • 33(25):10483–10489 • 10487

Table 1. PPI using the right amygdala as a seed region ( p(FWE) < 0.05 , cluster
extent threshold k > 10)
Anatomical label

Side

MNI coordinates

b

Right
Right
Right
Right
Right
Right
Right
Right
Right
Right
Right
Left
Left
Left
Right
Right
Left

56;
48;
54;
36;
38;
38;
42;
44;
42;
32;
42;
⫺10;
⫺12;
⫺12;
8;
6;
⫺8;
0;
⫺4;
⫺16;
12;
⫺24;
14;
14;

Temporal pole
Rolandic operculum
Rolandic operculum
Hippocampus
Brodmann area 13
Insula lobe
Insula lobe
Rolandic operculum
Insula lobe
Hippocampus
Insula lobe
Culmen
Cerebellum
Cerebellum
Cerebellum
Cerebellum
Culmenb
Periaqueductal grayb
Locus ceruleusb
Cerebellumb
Cerebellumb
Cerebellumb
Lingual gyrusb
Lingual gyrus

Left
Left
Right
Left
Right
Right

4;
0;
6;
⫺6;
2;
30;
2;
⫺12;
14;
⫺10;
⫺14;
⫺44;
⫺46;
⫺82;
⫺38;
⫺42;
⫺56;
⫺32;
⫺34;
⫺54;
⫺46;
⫺50;
⫺68;
⫺66;

z-score
⫺2
14
2
⫺22
⫺24
6
0
16
2
⫺18
4
⫺26
⫺22
⫺32
⫺28
⫺26
⫺24
⫺28
⫺26
⫺26
⫺8
⫺28
2
⫺10

5.47
5.45
5.4
5.27
5.25
5.2
5.14
5.09
5.05
5.01
4.96
5.4
5.34
5.14
5.12
5.09
5.03
4.92
4.85
4.83
4.81
4.76
5.18
4.32

Coordinates of PPI peaks with respect to the comparison DG ⬎ AG. Original PPI has been normalized in the MNI
space.
b
Peak voxels of cluster, followed by subpeak voxels a minimum of 8 mm apart.
a

lateral aspect, responds more strongly to faces making eye contact
than those presenting an AG, using behavioral and brain imaging
investigations.
Several studies have emphasized a link between the amygdala,
emotions, and gaze processing. Direction of gaze modulates our
judgment regarding the intensity of an emotion (Adams and
Kleck, 2005); and vice versa, different emotions modify our judgment regarding the direction of gaze (Lobmaier et al., 2008; Lobmaier and Perrett, 2011). These behavioral findings have been
corroborated by imaging studies showing that the amygdala response to emotional expressions is modulated by the direction of
gaze (Adams and Kleck, 2003; Hadjikhani et al., 2008; Adams et
al., 2012). However, in the present study, it is eye contact per se,
independently of any emotional expression, that appears to be
the critical stimulus. This is not surprising given that gaze is a
form of social communication in its own right. For example,
investigations have shown that DG produces a greater cortical
arousal based on EEG (Gale et al., 1978). Furthermore, DG is
associated behaviorally with threat and dominance, inducing
avoidance behavior under certain circumstances (reviewed by
Kleinke, 1986).
In line with this, imaging studies in healthy controls have
found amygdala activity in response to gaze direction with strictly
neutral faces as well. In a PET study, Kawashima et al. (1999)
compared brain activation in healthy controls who watched videos of a person whose gaze was either averted or directed to the
viewer while they judged where the person was looking. When
subjects determined gaze direction, the left amygdala was found
to be activated relative to a control condition. This was observed
whether or not eye contact was made. By contrast, when DG was
specifically contrasted with AG, the right amygdala was found to
be activated. Subsequently, George et al. (2001) investigated the
BOLD response of subjects who viewed photographs of faces with

DG or AG. Compared with AG, DG yielded a stronger activation
in ventral occipitotemporal cortices around the fusiform gyrus,
activity that was also highly correlated with amygdala activity.
Nevertheless, not all studies have reported amygdala activity
when investigating eye contact. Hoffman and Haxby (2000) presented faces with DGs or AGs to their participants, under conditions of passive viewing, or of selective attention to identity or
gaze. Overall, their results showed that gaze and identity activated
a network of face-processing regions, which comprised the inferior occipital gyrus, lateral fusiform gyrus, and superior temporal
sulcus (STS). With regard specifically to gaze processing, we
found that passive viewing of AG compared with DG gave rise
notably to an increase in left STS activation. STS was interpreted
as the structure involved in processing changeable aspect of faces,
an explanation that is in line with neurophysiological findings in
monkeys (Perrett et al., 1985; Heywood and Cowey, 1992). As the
authors point out, the amygdala was not included in their scans;
therefore, its contribution cannot be determined. Pageler et al.
(2003) performed a similar experiment in which the direction of
both the face and gaze were averted or directed to the viewer. The
fusiform gyrus and STS both responded to the direction of the
face independently of gaze. An effect of eye contact was found but
only when faces were also directed toward the viewer. This response was located in the fusiform gyrus, although no amygdala
activation was detected.
Consequently, although a certain discrepancy exists in the
literature regarding the cerebral regions involved in gaze processing in healthy controls, the results point to a likely involvement of
the right amygdala for DG, suggestions that are corroborated by
our current investigation. Furthermore, the correlation of
amygdala activity with known core face processing areas in our
study is in line with another a number of previous reports in the
field (Hoffman and Haxby, 2000; George et al., 2001; Pageler et
al., 2003).
First and foremost in our study, however, is the finding that
amygdala activation occurs regardless of the loss of V1. One plausible explanation for this stems from a suggestion put forward by
LeDoux (1996) that a coarse but rapid subcortical pathway, bypassing V1, might convey information about potentially threatening stimuli to the amygdala, allowing appropriate response
behavior to be implemented more quickly. In case of damage to
the primary sensory cortices, this route would allow behaviorally
relevant stimuli to be processed without awareness. Strikingly,
the existence of a response for DG in our study demonstrates that
eye contact belongs to this general category of relevant stimuli
along with emotional facial expressions and that blindsight for
gaze can occur.
In Patient T.N., affective blindsight was previously observed,
and data had revealed that emotional faces activated his right
amygdala despite his cortical blindness (Pegna et al., 2005), which
seemed to support the existence of such a subcortical route. Evidence from another blindsight patient was obtained by Morris et al.
(2001) showing amygdala activation for unseen faces that was correlated with activity in the superior colliculus and pulvinar, thereby
supporting the existence of a colliculo-pulvino-amygdalar pathway
in blindsight.
Lately, the existence of this subcortical route has been the subject
of considerable debate, and other pathways (e.g., thalamoextrastriate routes) have been put forward as possible alternatives) (Pessoa and Adolphs, 2010; Tamietto and de Gelder, 2010).
More recently, however, a diffusion tensor imaging study was
performed on another, unilateral blindsight patient (G.Y.) as well
as a group of controls. Neural connections between the superior

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Burra et al. • Amygdala Activation for Eye Contact

colliculus, pulvinar, and amygdala were
found in both the control group and the
patient. The modifications observed in
the patient suggested that this pathway
could indeed constitute the basis for the
residual function observed in affective
blindsight (Tamietto et al., 2012). Although our current study does not allow a
precise pathway to be established, it nevertheless demonstrates unequivocally that
certain categories of stimuli do not necessitate the primary visual cortex to access
the amygdala. Eye contact clearly belongs
to this category.
Along the lines suggested by LeDoux
(2012), if eye contact represents a possible
threat, it would thus constitute a key stimFigure 4. BOLD response in a group of 10 healthy age-matched men for the contrast gaze straight ⬎ gaze averted ( p ⬍ 0.001,
ulus that could be processed automati- cluster extent threshold ⬎ 10 voxels). In a random model, we demonstrated that the classic regions related to the gaze contact are
cally to trigger the appropriate responses. activated. The right amygdala complex is also activated, but additional activation is revealed (left amygdala and hippocampus,
As noted by LeDoux (2012), the circuits right fusiform area). Some regions close to the region revealed during the PPI on the Patient T.N.’s right amygdala are activated.
underlying defense responses triggered by
unconditioned threat stimuli would inTable 2. Significant differences in BOLD response for direct versus averted gaze
clude the lateral amygdala, as well as the periaqueductal gray that
(uncorrected p < 0.001, with a cluster extent threshold of 10 voxels)
constitutes part of the defensive response, both of which were
Anatomical label
Side
MNI coordinates
z-score
found to be active in our study.
a
Hippocampus
Left
⫺22;
⫺16;
⫺18
3.69
The amygdala (and periaqueductal gray) that we observe
Amygdala
Left
⫺32;
⫺6;
⫺20
3.67
could therefore be part of an automatic defense circuit operating
Parahippocampal gyrus
Left
⫺30; ⫺28; ⫺16
3.4
without awareness and without detailed processing by the priRight
8; ⫺6; 0
4.23
Thalamusa
mary visual cortex. Indeed, the amygdala can be triggered by
Left
⫺28; ⫺84; 4
4.19
Middle occipital gyrusa
relatively crude stimuli. For example, Vuilleumier et al. (2003)
Right
34; ⫺48; ⫺12
4.15
Fusiform gyrusa
showed that the low spatial frequency components of a fearful
Right
46; 2; ⫺8
3.79
Posterior insulaa
Right
6; 6; 6
3.73
White matter (anterior commissure)a
face were sufficient to trigger an amygdala response. However,
Right
6; ⫺2; ⫺16
3.52
Hypothalamusa
our results showed that spatial frequency had no effect on the
Parahippocampal
gyrus
Right
16;
⫺2;
⫺20
3.2
fMRI response (the effect of gaze direction on amygdala activaRight
24; ⫺14; ⫺20
3.46
Hippocampusa
tion was equally strong in all three filtering conditions). Thus, in
Right
24; ⫺86; ⫺6
3.42
Lingual gyrusa
our study, the relevant visual cues did not appear to depend
a
Peak voxels of cluster, followed by subpeak voxels a minimum of 8 mm apart.
strictly on the low spatial frequency components, which appears
to argue against the view that the amygdala relies solely on coarse,
low spatial frequency information. However, Whalen et al.
circuit underlying defense responses without information from
(2004) observed that the whites of eyes expressing fear produced
V1 and thus without awareness.
a greater response in the amygdala compared with eye whites of
happy expressions. This was observed even though the stimuli
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