In the present study we found that TD children show marked regional increases in brain activity in response to negative emotional expressions conveying direct as opposed to averted gazes, where the facial expressions were otherwise identical. Sensitivity to this subtle stimulus alteration suggests that the significance of direct eye gaze in emotionally expressive faces is powerfully registered in the young brain during face processing. Interpreting and responding accordingly to whether or not cues conveyed about others’ mental or emotional states relate immediately to you or your actions is essential for successfully navigating a dynamic and complex social world. Processing direct gaze in faces displaying negative emotions generates a strong neural signature in the TD brain, marked by activity in a network of emotion-processing regions. The dynamic gaze-related component of face processing has been elegantly described and replicated in studies using moving eye stimuli, highlighting the importance of social context on neural response in both the adult and TD brain (Pelphrey et al. 2003
; Mosconi et al. 2005
Interestingly, brain activity in VLPFC in TD children was solely dependent on eye gaze direction in angry or fearful faces. VLPFC has been observed to respond during the labeling of negative emotions (Hariri et al. 2000
), as well as while interpreting others’ mental or emotional states on the basis of these emotions (Sabbagh 2004
), and is associated in both children and adults with enhanced cognitive control and suppression of undesired behavioral responses (e.g., Bunge et al. 2002
; Aron et al. 2004
). The relevance of gaze in processing the immediate threat and meaning of these negative emotional expressions suggests that differential activity in VLPFC may code or respond to the immediate, communicative significance of these emotional expressions. The results of this study suggest that in TD children, eye gaze cues may powerfully influence brain responses directly contributing to these interpretive and regulating functions within a social context.
The region in VLPFC differentiating direct and averted gaze in TD children also differentiated the TD from ASD group activation during direct gaze. Although children with ASD attended to the same visual information and fixated equally on the features of the face as did TD children (as confirmed in a separate eye tracking session), our data suggest that the particular significance of the emotional information conveyed by the faces with direct gaze may have been processed differently by TD children. A direct gaze conveying a strong, negative emotion has immediate significance for the individual, signaling potential threat and critical social information (i.e., I am in trouble; I have done something wrong; someone is angry at me, etc.). The same facial expression conveyed with an averted gaze changes the significance of that information, tagging it as less immediately relevant to the receiver. In our sample of TD children, VLPFC activation appears to occur not merely as a result of exposure to negative affect, but rather to negative affect that is perceived to be directly relevant to the individual. In autism, it appears that processing this information in others’ faces, likely relying in part on regions sensitive to gaze direction, is abnormal or absent, even when visual perception is clearly intact.
Activity in VLPFC has been found in previous studies to show an inverse relationship with activity in the amygdala in nonclinical samples while processing negative affect faces (Hariri et al. 2000
and Kim et al. 2004
), supporting an emotional response regulation function of this region. We find activity in both
VLPFC and the amygdala to be significantly reduced, however, while children with autism process fearful or angry faces, relative to typical levels, and that this difference is most pronounced in the processing of faces with direct gaze. Studies have reported heightened sensitivity to direct gaze in regions such as the amygdala and striatum in autism, supporting a gaze aversion hypothesis whereby individuals with autism avoid mutual gaze with others due to the overly arousing or aversive nature of such eye contact (e.g., Dalton et al. 2005
). However, findings regarding responsiveness to these cues in the amygdala and purported arousal have been mixed. If individuals with ASD have reduced eye fixation due to hyperarousal to these cues, then we would predict that with equal amounts of eye fixation across groups, exposure to expressive faces with direct gaze in a group of ASD children should cause an increased
response in the amygdala and other regions associated with anxiety and inhibitory regulation—not only relative to that in TD children, but also relative to response to the same faces with averted gaze. Our results do not support this hypothesis of anxiety-associated social aversion in autism. Rather, our results are more consistent with the reduced social motivation hypothesis (Dawson et al. 1998
), in line with recent evidence indicating that social stimuli (e.g., a smiling face) fail to elicit activity in the reward system in children with ASD (Scott-Van Zealand et al. 2010
). The present results extend this hypothesis by suggesting that children with ASD may engage in less-direct eye contact in part because they do not extract the communicative intent from direct gaze cues as do TD children, leaving the eyes no more informative or interesting than any other facial feature.
Our finding of reduced activity in VLPFC in the ASD group while viewing direct-gaze faces, despite equal engagement of visual cortex and fusiform gyrus, are consistent with other reports showing reduced spontaneous inferior-frontal and medial temporal lobe activity while children with ASD interpret others’ mental or emotional states (Wang et al. 2004
). Our results are not likely explained by decreased fixation on the eyes or faces in the children with ASD, as indicated by a separate eye tracking session. It cannot be ruled out that differences in activation may have been related to decreased perception or judgment
of gaze direction in the ASD group, as has been suggested by a recent study on gaze processing in individuals with autism (Ashwin et al. 2009
). This possibility of reduced discriminative ability in ASD between direct and averted gaze, however, likely represents a related aspect of decreased sensitivity to gaze cues and their associated communicative significance, and thus might be expected given the findings of the current study.
An additional concern that emerges from comparing a clinical sample with a group of TD children is that the observed differences may be due to generally reduced brain response in the experimental group. This did not appear to be the case in our data, however, as the observed reductions in VLPFC, caudate, and other areas were regionally specific, with activity in other visual- and face-processing regions found to be comparable between groups. Additionally, the children with autism in our study recruited other brain regions to a greater degree than TD children while viewing faces with averted gaze. At even the highest thresholds explored, significantly increased activity relative to that in the TD group was observed within somatosensory cortex (BA 2). As our paradigm encouraged each group to fixate on the eyes, these fMRI findings of somatosensory cortical activation in the ASD group are consistent with data from previous fMRI and eye tracking studies suggesting that children with ASD, unless otherwise instructed, may spontaneously use alternative strategies to process or interpret information in faces (e.g., Klin et al. 2002
; Pelphrey et al. 2002
; Wang et al. 2004
; Dapretto et al. 2006
; Wang et al. 2007
). Further investigations of the fixation behavior of children with autism while viewing faces not only of varying emotions but also of varying eye gaze may be fruitful in identifying these potentially unique strategies. Furthermore, employing eye and emotion-related dynamic facial stimuli rather than stationary faces, as in the present study, may enrich our preliminary understanding of how dynamic gaze and emotion cues may modulate one another in the brain (Pelphrey et al. 2007
The findings of our study are also in line with other data reporting decreased frontal brain activity in children with autism to emotional and social cues, suggesting that children who develop autism may have reduced integrity of frontal-posterior brain connections (Just et al. 2004
). Several fMRI studies in autism have reported reduced left IFG activity in response to social cues, and both functional and structural data have supported a dysregulation model, whereby desynchronized and reduced prefrontal response during social tasks are results of distally reduced, and possibly locally increased, cortical connectivity (Courchesne et al. 2001
; Herbert et al. 2004
; Just et al. 2004
). The results of our study are consistent with this theoretical explanation, but cannot directly address it.
Our experimental set-up with cross-hair fixation points preceding eye stimuli was designed to prevent gaze aversion or reduced fixation on the eyes in the ASD group, and our eye tracking data showed no group differences in gaze behavior in either gaze direction condition, making it unlikely that gaze aversion could have explained our results. Equivalent activation among ASD and TD children in visual-processing regions including the fusiform gyrus, which is critical for processing faces, further suggests that ASD and TD children spent equal time looking at the faces. Our inability to track eye fixation in the scanner during the fMRI sessions, however, represents a weakness of this study, which our separate eye tracking data can only indirectly address. Based on the eye-tracking findings, the fixation cross manipulation in our design may have helped equate fixation behavior between groups, as might have the fact that the ASD group represented a relatively high-functioning sample of children who, even without the fixation crosses, may not have demonstrated as dramatic fixation deviations as has been found in lower-functioning samples (Boucher and Lewis 1992
We found that the amount of time that children tended to fixate on the face or particular regions of the face (as measured in the separate eye tracking session) did not relate in either group to brain activity in the amygdala, right VLPFC, or left VLPFC. Children with ASD who tended to look more at the eyes during direct gaze faces as a proportion of time spent looking at other regions such as the nose or forehead, however, did show significantly increased activation in right VLPFC during the presentation of negative, direct-gaze expressions. The presence of this relationship when eye gaze is quantified as a fixation preference, but not when it is quantified in terms of raw time, points to the possibility that children with a more normative bias to attend to eyes also show more normative brain activity. Children who overall attended to the faces less, but gazed more exclusively at the eyes when doing so, or children who attended well to the faces but showed a more distributed pattern of fixation did not show this associated increase in activation in VLPFC.
As the first study to directly address how gaze may be processed along with emotional content in TD children and children with autism, our results suggest that high-functioning children with ASD may perceive the faces and gaze direction, but that this information may not be automatically translated into its communicative significance through the co-recruitment of prefrontal and limbic brain regions, as appears to occur in children without ASD. If this is the case, deficits in social comprehension and functioning may not result directly from avoiding the eyes, or having a physiological aversion to direct gaze, but rather because the significance of emotional expressions with direct gaze are not extracted from their corresponding facial cues. This would suggest that at least by later childhood, reduced mutual gaze might be due to the fact that observing direct gaze in another person is no more meaningful or rewarding than observing a gaze that is averted. The differences we report between neurotypical children and children with ASD who display marked social impairments highlight the importance of appropriate sensitivity to the eye gaze in navigating the social world and suggest that disordered development in ASD may directly result from failure to appropriately respond to these subtle social cues.