Neural Disconnection and Errant Visual Perception in Psychotic Psychopathology

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 DESCRIPTION (provided by applicant): Errant perception is a defining feature of severe psychopathology and contributes to distortions of reality experienced by individuals with psychosis. Growing evidence indicates that individuals with psychotic disorders have compromised neural connectivity which is associated with hallucinatory experiences - a prominent form of reality distortion. Although the precise neural circuitry that gives rise to perceptual errors and hallucinations is unknown, anomalous interactions of low-level sensory and high-level cognitive processes appear to contribute to these distortions of reality. This project will use psychophysical tasks and magnetic resonance imaging (MRI) data to quantitatively model the role of low-level and high-level influences on visual perceptual abnormalities in psychosis. The model will be constrained through incorporating new knowledge of structural and functional neural connections relevant to visual perception. The goal of the proposed work is to develop and test quantitative models of local and long-range neural mechanisms that account for visual misperception in psychosis through the use of Human Connectome Project (HCP) acquisition protocols and psychophysical tasks. The project involves two specific aims. The first aim is to expand the HCP data repository by contributing MRI data from 150 people with psychotic psychopathology, 100 first-degree biological relatives of psychotic participants, and 50 healthy non-psychiatric controls. Imaging data will be collected using the 2-hour HCP Washington University (WU) Lifespan protocol on a Siemens Prisma scanner. These data will enable direct comparison between healthy controls, individuals with psychosis, and individuals with genetic liability for psychosis with existing HCP Lifespan data. Access to existing HCP Lifespan data will make possible characterization of normal variability in visual cortical connectivity and facilitate standardized assessment of neural networks. The second goal is to acquire functional MRI data during visual tasks using a 7 Tesla magnet and the same sequences and scanner used for the UMinn 7T Lifespan protocol in order to quantitatively model the role of local and long-range functional connectivity in visual misperception, as well as relate model parameters to dimensional variation in perceptual anomalies associated with psychosis. Combined use of 7T HCP data and a testable neurophysiological quantitative model of visual anomalies will yield unprecedented specificity in delineating mechanistic circuitry giving rise to psychotic symptomatology. Inclusion of the broader HCP Lifespan data set and a tested generalized quantitative model will provide a means for direct examination by other investigators as well as facilitate standardized and individualized assessment of functional connectivity anomalies pertinent to the development and expression of psychosis.