Functional magnetic resonance imaging of brain responses to biological motion in children with autism spectrum disorder (ASD), unaffected siblings (US) of children with ASD, and typically developing (TD) children has revealed three types of neural signatures: (i) state activity, related to the state of having ASD that characterizes the nature of disruption in brain circuitry; (ii) trait activity, reflecting shared areas of dysfunction in US and children with ASD, thereby providing a promising neuroendophenotype to facilitate efforts to bridge genomic complexity and disorder heterogeneity; and (iii) compensatory activity, unique to US, suggesting a neural systemlevel mechanism by which US might compensate for an increased genetic risk for developing ASD. The distinct brain responses to biological motion exhibited by TD children and US are striking given the identical behavioral profile of these two groups. These findings offer far-reaching implications for our understanding of the neural systems underlying autism.endophenotype | functional magnetic resonance imaging

The expression of autism spectrum disorder (ASD) is highly heterogeneous, owing to the complex interactions between genes, the brain, and behavior throughout development. Here we present a model of ASD that implicates an early and initial failure to develop the specialized functions of one or more of the set of neuroanatomical structures involved in social information processing (i.e., the “social brain”). From this early and primary disruption, abnormal brain development is canalized because the individual with an ASD must develop in a highly social world without the specialized neural systems that would ordinarily allow him or her to partake in the fabric of social life, which is woven from the thread of opportunities for social reciprocity and the tools of social engagement. This brain canalization gives rise to other characteristic behavioral deficits in ASD including deficits in communication, restricted interests, and repetitive behaviors. We propose that focused efforts to explore the brain mechanisms underlying the core, pathognomic deficits in the development of mechanisms for social engagement in ASD will greatly elucidate our understanding and treatment of this complex, devastating family of neurodevelopmental disorders. In particular, developmental studies (i.e., longitudinal studies of young children with and without ASD, as well as infants at increased risk for being identified with ASD) of the neural circuitry supporting key aspects of social information processing are likely to provide important insights into the underlying components of the full-syndrome of ASD. These studies could also contribute to the identification of developmental brain endophenotypes to facilitate genetic studies. The potential for this kind of approach is illustrated via examples of functional neuroimaging research from our own laboratory implicating the posterior superior temporal sulcus (STS) as a key player in the set of neural structures giving rise to ASD.

The posterior superior temporal sulcus (STS) region plays an important role in the perception of social acts, although its full role has not been completely clarified. This functional magnetic resonance imaging experiment examined activity in the STS region as participants viewed actions that were congruent or incongruent with intentions established by a previous emotional context. Participants viewed an actress express either a positive or a negative emotion toward one of two objects and then subsequently pick up one of them. If the object that was picked up had received positive regard, or if the object that was not picked up had received negative regard, the action was congruent; otherwise, the action was incongruent. Activity in the right posterior STS region was sensitive to the congruency between the action and the actress’s emotional expression (i.e., STS activity was greater on incongruent than on congruent trials). These findings suggest that the posterior STS represents not only biological motion, but also how another person’s motion is related to his or her intentions.

Mentalizing, in particular the successful attribution of complex mental states to others, is crucial for navigating social interactions. This ability is highly influenced by external factors within one's daily life, such as stress. We investigated the impact of stress on the brain basis of mentalization in adults. Using a novel modification of the Reading the Mind in the Eyes Test (RMET-R) we compared the differential effects of two personalized stress induction procedures: a general stress induction (GSI) and an attachment-related stress induction (ASI). Participants performed the RMET-R at baseline and after each of the two inductions. Baseline results replicated and extended previous findings regarding the neural correlates of the RMET-R. Additionally, we identified brain regions associated with making complex age judgments from the same stimuli. Results after stress exposure showed that the ASI condition resulted in reduced mentalization-related activation in the left posterior superior temporal sulcus (STS), left inferior frontal gyrus and left temporoparietal junction (TPJ). Moreover, the left middle frontal gyrus and left anterior insula showed greater functional connectivity to the left posterior STS after the ASI. Our findings indicate that attachment-related stress has a unique effect on the neural correlates of mentalization.

Previous research suggests hypoactivity in response to the visual perception of faces in the fusiform gyri and amygdalae of individuals with autism. However, critical questions remain regarding the mechanisms underlying these findings. In particular, to what degree is the hypoactivation accounted for by known differences in the visual scanpaths exhibited by individuals with and without autism in response to faces? Here, using functional magnetic resonance imaging (fMRI), we report “normalization” of activity in the right fusiform gyrus, but not the amygdalae, when individuals with autism were compelled to perform visual scanpaths that involved fixating upon the eyes of a fearful face. These findings hold important implications for our understanding of social brain dysfunction in autism, theories of the role of the fusiform gyri in face processing, and the design of more effective interventions for autism.