Neural substrates of deficits in naturalistic social cognition in schizophrenia

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Project Summary: Psychiatric disorders such as schizophrenia are often marked by poor social cognition, but little is known about the neural mechanisms underlying these deficits. Visual scanning of social scenes for relevant social cues is a key domain of social cognition, and is necessary to detect and use social cues to understand the thoughts and feelings of others in the social scene (mentalization). The targeting of those eye- movements are often driven by facial expressions of emotion, which are salient, or stand out from other visual features, and are behaviorally relevant, or known to contain information useful for understanding the social situation. Recent work from my lab has found abnormalities in the visual scanning of naturalistic social scenes (movies of staged social scenes) in schizophrenia, which resulted in decreased detection of facial expressions and affected understanding of those scenes. I have also found gross functional deficits in the temporoparietal junction/posterior superior temporal sulcus (TPJ-pSTS), a region of the brain that contains brain areas related to the perception of facial expressions of emotion, guiding of eye-movements, and mentalization. This grant application aims to build on these findings by investigating the functional integrity of the cortical areas involved in the transformation of the visual information into plans for saccadic eye-movements in individuals with schizophrenia versus demographically matched healthy controls. I am proposing to perform a combination of free-viewing naturalistic and rigorously controlled psychophysical experiments to study these areas. We will use techniques that my lab has adapted from Dr. David Leopold and others to separately assess the integrity of the TPJ-pSTS in the visual processing, communications with other areas, and generation of saccades during free-viewing of movies. We will also examine the organization and functioning of the dorsal attention areas that control eye-movements. These frontoparietal areas are retinotopically mapped, meaning that they contain a 1:1 map of the visual field centered on the fovea of the retina. With Dr. Clayton Curtis, I will map these areas in each individual, and then examine whether the activity within these maps mirrors the salient and behaviorally relevant visual features in the movies viewed by the participants. Lastly, we will examine whether failures in visual scanning in SzP are related to deficits in the functioning of the TPJ-pSTS, dorsal attention areas, or both. The proposed experiments address several unmet needs outlined in the NIMH Strategic Objectives. The results of the proposed experiments will provide (as far as we know) the first full circuit-level map of a complex behavior that has direct psychiatric relevance. The results will also shed light on possible microcircuit deficits that may lead to retinotopic map abnormalities. With this information, I will then be able to design low- burden tests of social functioning easily deployed in clinical settings, and also start investigating rehabilitation or neuromodulation treatments to repair or compensate for these social cognition deficits in schizophrenia.