PROJECT SUMMARY Schizophrenia is a severe and debilitating psychotic disorder, characterized by disturbances of the basic sense of self and social disconnection throughout the course of illness. The proposed project aims to elucidate the impact of self-disturbances in social impairments by focusing on one core aspect of the bodily self, the self-other boundary. An implicit awareness of clearly defined self-boundary is a prerequisite for adaptive interactions with the external world. In individuals with schizophrenia, however, a disrupted self-other boundary complicates the process of distinguishing one’s own behaviors from those of others, thereby undermining social interactions. Loss of social opportunities often leads to social isolation, which further erodes interpersonal relationships and exacerbates self-disturbances, setting up a destructive cycle. Despite the chronicity and prevalence of self-disturbances and social impairments in schizophrenia, common mechanisms underlying disrupted self-other distinction and social impairments have not been extensively investigated. One major hurdle has been a lack of methodological tools to quantify the subjective phenomenology of self-disturbances. We will utilize novel behavioral methods and leverage the technological advances in immersive virtual reality (VR) to investigate two core aspects of self-other interactions in space: (1) the implicit multisensory action space around the self that determines one’s self-other boundary (peripersonal space); (2) the social construct of the interpersonal comfort space (interpersonal distance). To estimate the implicit self- boundary in our participants, we will implement a basic visuo-tactile integration paradigm in VR adapted from neurophysiological studies of multisensory neurons in nonhuman primates. To assess the social comfort space that determines interpersonal distance, we will use the stop-distance paradigm in VR. This approach will allow us to quantify the self-other boundary in the context of social interactions and link to their neural correlates. We will specify mechanisms that connect these constructs to identify more precise targets for treatment. Systematic examination of the peripersonal space and its relation to interpersonal distance regulation may be a first step towards identifying the role of self-disturbances in components of disrupted social behavior. This project will utilize mechanisms underlying multisensory integration processes to understand complex social behavior. Self‐disturbances are common features of a wide range of neuropsychiatric conditions. Indeed, all forms of psychiatric disorders may be conceptualized as maladies of disrupted social homeostasis between the self and the social world. Thus, this approach may be broadly applicable across multiple neuropsychiatric conditions that intersect with self-disorders and social impairments and will contribute towards the goals of the NIMH Research Domain Criteria (RDoC) strategy.

PROJECT NARRATIVE Self-disturbances and social impairment are two core features of schizophrenia that contribute to the heavy personal and societal burden of long-term disability, but there are currently no effective interventions to ameliorate social deficits or self-disturbances of schizophrenia despite their detrimental impact on functional outcome. We will examine a quantifiable component of self-disturbances (self-other boundary) in relation to interpersonal distance regulation by implementing multisensory integration tasks in an immersive virtual reality environment and by utilizing functional neuroimaging to characterize underlying mechanisms that may lead to anomalous self-other processing and social disconnection. Elucidating how maladaptive social interactions may arise from basic problems of multisensory integration (i.e. disrupted self-other boundary) could lead to a more precise treatment targets, and therefore, contribute towards reducing social disability of individuals with conditions that disrupt self-other processing such as schizophrenia.