Whole-brain functional connectomic investigation of cognition in psychosis risk
Hwang, Melissa Hsin-Wei
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BACKGROUND: Cognitive deficits are a core component of schizophrenia and among the strongest determinants of functional disability in psychotic illnesses. In particular, impairment in information processing speed has been demonstrated to be among the most significant in patients. Poor processing speed not only frequently occurs prior to psychosis onset during the prodromal or clinical high risk phase of psychotic illness, it has also been found to be a strong predictor of conversion to psychosis. However, the neurobiological basis of impaired processing speed in the clinical high risk population is not well understood. Functional connectivity during resting state fMRI provides useful insights into the organization and communication between brain regions that may elucidate the brain circuit basis underlying processing speed. OBJECTIVE: To identify the strongest link between brain functional connectivity and a measure of information processing speed in individuals at clinical high risk for conversion to psychosis by utilizing a data-driven analysis. METHODS: Cognitive and resting state fMRI data were collected from 198 clinical high risk participants and 123 neurotypical controls in the second phase of the North American Prodromal Longitudinal Study. Processing speed was measured by the Brief Assessment of Cognition in Schizophrenia Symbol Coding task. A multivariate pattern analysis was used to identify, at the individual voxel level, how functional connectivity correlates with information processing speed. RESULTS: Clinical high risk participants demonstrated significantly reduced processing speed, relative to neurotypical controls. Similarly, at risk patients who later converted to psychosis (n=17) also showed poorer performance on the BACS Symbol Coding task compared to non-converters. The strongest whole-brain link between connectivity and processing speed within the clinical high risk population was the bilateral amygdala. Specifically, connectivity between the bilateral amygdala and a functional brain network known as the salience network correlated with processing speed. CONCLUSIONS: Functional connectivity between the bilateral amygdala and the salience network was linked to individual variation in processing speed in the clinical high risk population. This affirmed a growing literature that implicates amygdala involvement in cognitive function and provides a potential biomarker for psychosis risk prior to diagnosis.