Behavioral and Neural Correlates of Deficits in Naturalistic Visual and Auditory Social Cognition in Individuals at Clinical High-Risk for Schizophrenia

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Deficits in social cognition are a major source of disability and suffering in individuals at clinical high-risk for developing schizophrenia (CHR). Like schizophrenia itself, this state is associated with a high rate of social functioning deficits that have a life-long impact. However, little is known about the behavioral and neural correlates of these deficits in this population, and there are few if any treatments. In this project we will adapt techniques we developed that use naturalistic stimuli, including movie clips and spoken word stories, to measure behavioral and neural correlates of social cognition. In schizophrenia we have so far found profound deficits in the eye-movements used to visually scan naturalistic videos of social scenes for social cues (such as facial expressions of emotion) and comprehension of auditory expressions of emotion that relate to overall social cognition deficits. We have also found large functional and resting state functional connectivity deficits in the temporoparietal junction/posterior superior temporal sulcus (TPJ-pSTS), an area that serves as a hub for social cognitive operations like visual scanning. This region also fully matures in early adulthood around the age of most CHRs, suggesting that developmental failures at this age may have lasting effects. We will use a combination of behavioral, functional, and connectivity measures to examine auditory and visual social cognition in the CHRs in comparison to participants early in their psychotic illness (EPs) and demographically matched healthy controls (HCs). We will measure comprehension of short video clips of social situations, visual scanning performance, detection of auditory sarcasm, TPJ-pSTS activity evoked by both a visual only movie clip and an audio only spoken word story, and TPJ-pSTS resting state functional connectivity. The first aim will be to compare these measures between the three populations. The second aim will be to study how the eye-tracking/visual scanning and auditory sarcasm measures (and the TPJ-pSTS functional and connectivity correlates) predict social cognition at baseline and again in two years' time. The third aim will be to repeat these measures in the CHR individuals who develop schizophrenia, along with a subset of the HCs. Based on pilot results, we hypothesize that visual-related measures (visual scanning, TPJ- pSTS movie-watching activity, TPJ-pSTS connectivity) will be mildly impaired but auditory measures heightened compared to HCs, leading to overall similar social cognition at baseline, whereas in EPs will be profoundly affected in all measures. Furthermore, we hypothesize that visual scanning measures will segregate the CHRs into two groups, one similar to HCs and one similar to EPs. The latter group will be the source of most of the SzP converters, and the ones with profound deficits on repeat testing. In addition to clarifying the correlates of social cognition in this population, the impact of these experiments will be to open new avenues of early intervention on social functioning outcomes in this population based on correcting visual scanning patterns and neuromodulation of the TPJ-pSTS.