Friday, May 9, 2025
5/9/2025
Development of Cerebellar-Cortical Functional Connectivity in Youth and Its Prediction of Psychosis - Abstract Cerebellum dysfunction is known to be strongly implicated in the pathogenesis of psychosis. Our past research has provided converging evidence that functional dysconnectivity in the cerebellar-cortical circuitry is a robust neural anomaly that is ubiquitously manifest across different clinical stages and brain states in psychotic patients, predictive of psychosis onset, and related to genetic risk for psychosis. Therefore, cerebellar-cortical dysconnectivity is likely to reflect a pathological trait arising from abnormal neurodevelopment, emphasizing the importance of understanding the developmental trajectories of cerebellar-cortical connectivity and their associations with psychosis. To this end, we will utilize data from four large neurodevelopment datasets with resting-state fMRI scans and extensive clinical and cognitive assessments, including the Lifespan Human Connectome Project in Development (HCP-D), the Philadelphia Neurodevelopmental Cohort (PNC), the North American Prodrome Longitudinal Study Phase 3 (NAPLS-3) and NAPLS Phase 2 (NAPLS-2), with a total of > 3000 individuals from 5 to 21 years old. We will use the HCP-D dataset as the benchmark to chart normal development curves of cerebellar-cortical connectivity from childhood to early adulthood, and use the PNC dataset to comprehensively investigate how deviations from these normative curves predict psychotic-like symptoms and cognitive disturbances during neurodevelopment. The results will be summarized into individualized “cerebellar risk scores” and used for prediction of psychosis onset in the NAPLS-3 and NAPLS-2 datasets. Overall, the outcomes from this study will 1) provide detailed insights into the developmental patterns of cerebellar-cortical connectivity in typically and atypically developed youth; 2) bridge the gap between systems-level cerebellar dysfunction and its cognitive and symptom correlates during neurodevelopment; and 3) generate an individualized, generalizable, cerebellum-based risk score that can be leveraged for future psychosis prediction and early intervention studies.
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