1998; Klin et al. 2003). Neuroimaging studies by Schultz and others have offered partial support for such a hypothesis showing reduced activity in the region of the fusiform gyrus typically associated with face processing, a finding taken to reflect reduced social experience and face-processing specialization (Schultz et al. 2000; Grelotti et al. 2002; Pierce et al. 2001; Wang et al. 2004). These two hypotheses make different predictions about brain activity during gaze and emotion processing. The former suggests that direct gaze, particularly in faces displaying strong

affect, should produce hyperactivity in emotionally responsive brain regions, such as the Inhibitors,research,lifescience,medical amygdala and ventrolateral prefrontal Inhibitors,research,lifescience,medical cortex (VLPFC), areas known to be involved in emotion signaling, integration, and regulation (Bunge et al. 2002; Aron et al. 2004). The latter hypothesis predicts reduced responsiveness in these same neural systems to these stimuli. Previous studies have found reduced automaticity in recruiting social information processing regions such Inhibitors,research,lifescience,medical as the amygdala and frontal areas when presented with stimuli such as faces or voices (e.g., Dapretto et al. 2006; Wang et al. 2007). It

is not clear, however, how eye gaze and emotion cues are integrated in the TD brain when processing emotional expressions with different gaze directions, nor how such cues, both important when navigating social interactions, may be abnormally processed in the autistic brain. Given their potential impact on early intervention, interpretation, and treatment of individuals with autism, we sought to compare the predictions of the above two hypotheses and build upon previous work on gaze and emotion processing Inhibitors,research,lifescience,medical in children with

ASD, to help shed further light on the neural bases of these functions. More specifically, we performed fMRI during direct and averted Inhibitors,research,lifescience,medical gaze processing in children with ASD and TD controls to examine the impact of gaze direction on neural responses to social and emotional stimuli. Methods research Participants crotamiton Sixteen TD children (two female) between the ages of 8–17 years (mean age 12.30) were gender-, age-, and IQ-matched to our sample of 16 children with ASD. For each child in the ASD group, a prior clinical diagnosis was confirmed in an initial lab visit using the Autism Diagnostic Interview, Revised (Lord et al. 1994) and Autism Diagnostic Observation Schedule-Generic (Lord et al. 2000) (see Table 1 for subject demographic information, and Supporting information for diagnostic details). In our sample, eight children met research criteria for diagnosis of autism on both the ADOS and ADI, five met diagnosis for autism by ADI and for ASD by the ADOS, two met diagnosis for ASD on both the ADOS and ADI, and one met diagnosis for ASD by the ADI and for autism by the ADOS.