Project Grant R01MH138682

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.