Project Summary Autism spectrum disorder (ASD) is characterized largely by deficits in social interaction and communication. However, despite these clear behavioral differences it has been difficult to isolate differences in high-level social brain regions in ASD. One important area that has been under-studied is the perception of others’ social interactions. Recognizing others’ social interactions—directed, contingent actions between two or more people— is a core area of human cognition. Humans quickly and effortlessly extract a wealth of information when viewing a social interaction and use this information to guide their own actions. Social interaction perception is notably disrupted in autism, but the brain basis of these deficits are still unknown. Recently a region in the posterior superior temporal sulcus in neurotypical (NT) adults has been identified that is selectively engaged when viewing others’ social interactions in both controlled stimuli and during natural movie viewing. Critically, social interaction selectivity in the brain has never been studied in ASD. The long-term goal of this research is to understand the brain basis of social interaction perception in controlled and naturalistic contexts, and its disruption in autism. Our overall objective is to identify differences in neural response to social interactions in high-functioning individuals with ASD using both controlled and movie stimuli. Our central hypotheses are that social interactions engage the same region of the pSTS in NT subjects in both controlled and naturalistic settings, and that this activity is significantly decreased in autism. Aim 1 will identify the brain regions that selectively respond to social interactions in NT subjects using both controlled and natural movie fMRI paradigms. Advanced machine learning methods will isolate the unique neural contribution of social interactions during movie viewing, allowing the first direct comparison between controlled stimuli, the status quo in social neuroscience, and natural movie stimuli, an exciting new paradigm that is more ecologically relevant, better drives neural responses, and opens the door to studies of new populations, including children and more impacted individuals with autism . Aim 2 will identify the brain regions that are selective to social interactions in ASD subjects in controlled and movie stimuli and how they differ from neurotypical brain responses identified in Aim 1. The proposed study will provide us with a direct comparison of the neural basis of social interaction perception in controlled and naturalistic settings, as well as a clear understanding of the neural basis of social interaction perception in ASD. This work will also pioneer the use of natural stimuli for studies of neurodevelopmental disorders, creating a new framework to understand the neural basis of high-level social perception in a range of clinical populations.