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, 2004; 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

Inhibitors,research,lifescience,medical 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 Inhibitors,research,lifescience,medical results of this study suggest that in TD children, eye gaze cues may powerfully influence brain responses PCI32765 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 Inhibitors,research,lifescience,medical from ASD group activation Inhibitors,research,lifescience,medical 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 Inhibitors,research,lifescience,medical 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 the 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.