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 Selleckchem Venetoclax fixation due to hyperarousal to these cues, then we would predict that with equal amounts of eye fixation Inhibitors,research,lifescience,medical 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 Inhibitors,research,lifescience,medical 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 Inhibitors,research,lifescience,medical 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 Inhibitors,research,lifescience,medical 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 Inhibitors,research,lifescience,medical eye tracking not 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.