Cognitive mechanisms of delusion severity throughout recovery from an acute psychotic episode: a computational approach

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PROJECT SUMMARY Delusions are psychotic symptoms that contribute to significant emotional distress, poorer quality of life, functional impairment, hospitalization and violence. Delusions are treatment-resistant in many patients. Mechanistic understanding of delusion severity remains elusive, limiting treatment advancement. Abnormal belief updating is a proposed mechanistic framework of delusions with accumulating evidentiary support. Prior cross-sectional work has demonstrated altered belief updating ability and associated neurobiological abnormalities in psychotic disorder patients during cognitive tasks. However, it is unknown whether belief updating abnormalities are state-markers of delusional thinking that change over time, or represent stable cognitive traits that contribute to delusion-proneness. Answering this question can not only inform mechanistic models of delusions, but will guide targeted treatment development. This K23 mentored patient- oriented career development award proposes a longitudinal examination of delusion severity and belief updating in psychotic disorder patients recovering from an acute episode of psychosis. This project will use computational and functional neuroimaging (fMRI) approaches to 1) determine how belief updating parameters change throughout six months of recovery from an acute delusional state, and 2) characterize neurobiological correlates of belief updating parameters as symptom severity changes. The applicant is a licensed clinical psychologist with a background in using neuropsychological tasks and neuroimaging techniques to understand cognitive deficits across the psychosis spectrum. Her long-term career goal is to build an independent research program that employs sophisticated cognitive neuroscience techniques to test mechanistic models of psychosis, and then use that knowledge to develop and test novel interventions. In order to accomplish these short and long-term goals, the applicant requires additional training, as outlined in this proposal. Training areas include: 1) the computational and cognitive neuroscience of delusions, 2) longitudinal research design and statistics, and 3) intervention research to prepare the applicant for a translational research career. Training will include formal coursework, didactics, and on-site trainings, guided under a mentorship team of experts in the longitudinal cognitive neuroimaging of psychotic disorders, computational modeling of psychotic symptoms, and treatment of delusions. Mentored training and completion of the proposed project will provide the applicant the skills and experience necessary to launch a successful independent research career.