13 The majority of fMRI studies in ASDs indicate FG hypoactivity to faces14-22 and to facial expressions.15,20,23-25 However, other reports suggest no differences in FG activation to familiar faces,26-29 stranger faces

in the presence of an attentional cue,30 or when matching upright with inverted faces.31 These apparently inconsistent findings may be reconciled in a number of ways.32,33 The degree of visual attention to faces appears to be a critical factor moderating FG activation to faces in ASDs, with tasks Inhibitors,research,lifescience,medical that guide visual attention to faces or analytic approaches that account for point-of-regard resulting in relatively less FG hypoactivation in ASDs.21,30 This conclusion is supported by research indicating that face familiarity moderates FG responses to faces in ASDs28 and that impaired social cognition in ASDs may be mediated, Inhibitors,research,lifescience,medical at least in part, by attention to social cues, rather than by deficits in social cue processing per se.31,35 Similarly, lifelong amotivation to interact with faces may result in reduced perceptual skill when processing faces,

and, Inhibitors,research,lifescience,medical in turn, cause FG hypoactivation to faces in ASDs that is perhaps a downstream consequence of reduced social experience rather than pathognomonic to ASDs.36 Moreover, the FG encodes not only face percepts, but social check details knowledge as well,37 suggesting that the FG may mediate: (i) the attribution of social meaning to stimuli: (ii) the retrieval of social semantic information; and (iii) self-referential experiences.28 Thus, the disparate results of the face processing literature in ASDs likely reflect the diverse and subtle social processes mediated by the FG and recruited by diverse fMRI tasks. Amygdala response to faces Inhibitors,research,lifescience,medical in ASDs has also been extensively studied, and results in this area are decidedly mixed. There is evidence of no differences in amygdala activation to faces,18 of amygdala hypoactivation during face viewing15,16,26,31,38 and face matching,16

as well as evidence of amygdala hyperactivation to faces39,40 in ASDs, particularly Inhibitors,research,lifescience,medical when accounting for gaze time to faces21 (but see ref 41 for an exception). One study reported decreased amygdala habituation to the repeated MTMR9 presentation of faces, suggesting that social deficits in ASDs may be influenced by hyperarousal to faces due to protracted amygdala activation.42 Theory of mind Theory of mind and mental inferences have been examine in ASDs via fMRI studies that address the ability to infer feeling states and/or intentions (Table II), skills that typically develop during the first 4 or 5 years of life and that are critical for the development of social skills and for successful navigation of the social world.43 Such tasks include images, stories, and animations designed to elicit the attribution of mental states.