Project Summary It is unknown how functions of the brain give rise to psychotic experiences in severe psychopathology. Consequently, available treatments for psychotic disorders are often marginally effective. Abnormal visual perception is evident in psychosis (e.g., hallucinations) and noted in people with genetic liability for psychotic psychopathology (e.g., heightened illusions). Current evidence points to early visual abnormalities in psychosis that may trigger a cascade of errant neural activity creating distortions in one's visual experience; however, it is unclear how basic visual and complex guidance functions of the brain separately contribute to visual misperception in psychotic psychopathology. The overarching goal of the proposed work is to use sophisticated psychophysical tasks and neuroimaging to a) precisely characterize behavioral and neural abnormalities in individuals with psychotic disorders during visual perception, b) detail the mechanisms of visual hallucinations and distortions through the development and testing of a computational model c) determine if the mechanistic anomalies also mark genetic liability for psychosis. The goal will be accomplished by studying individuals with psychotic disorders (IPDs), one first-degree biological sibling of each IPD (SibIPDs), and healthy controls (HCs) demographically similar to the other two groups. We hypothesize that individuals prone to visual hallucinations exhibit stable neural abnormalities in early visual cortex (V1, V2) causing errors in the processing of visual elements, and that visual hallucinations occur in IPDs when contextual influences of more anterior regions (LOC/fusiform, prefrontal cortex) on visual perception become deviant. Individuals prone to anomalous visual illusions but without a psychotic disorder are hypothesized to exhibit a stable decrement in high-level influences on visual perception reflected in anomalies of inter-regional neural synchronization. We will employ contrast discrimination, surround suppression, attention regulation, and ambiguous object tasks to assess early visual perceptual processes, with and without contextual modulation, in IPDs, their unaffected biological siblings (SibIPDs), and healthy controls (HCs), to determine when task performance predicts self-reported visual misperceptions. We will compute cortical source signals from 248-channel MEG data functionally localized through 7 Tesla (T) fMRI to detail the location, timing, and synchronization of neural responses during visual perceptual tasks assessing local and long-range processes in IPDs, SibIPDs, and HCs, as well as determine how neural responses elicited by tasks predict variation in self-reported visual misperception. We will also characterize visual responses in all tasks using the Gaussian Scale Mixture model originally published by Schwartz et al (2009) and recently extended in our work to generalize across multiple scene segmentation cues (Qiu, 2013). We will use this model to test whether terms reflecting local inhibition are selectively reduced in all IPDs and whether the strength of the term representing long-range modulation correlates with frequency of visual hallucinations.