Heterogeneity in Functional Connectivity: Dimensional Predictors of Individual Variability during Rest and Task fMRI in Psychosis

Abstract

BackgroundIndividuals with schizophrenia spectrum disorders (SSD) often demonstrate cognitive impairments, associated with poor functional outcomes. While neurobiological heterogeneity has posed challenges when examining social cognition in SSD, it provides a unique opportunity to explore brain-behavior relationships. We examined the relationship between behavioral data and individual variability of functional connectivity at rest and during an emotional-processing task. MethodsNeuroimaging and behavioral data were analyzed for 193 individuals with SSD and 155 controls (total n = 348). Individual variability was quantified through mean correlational distance (MCD) of functional connectivity between participants; MCD was defined as a global variability score. Hierarchical regressions were performed on variability scores derived from resting state and Empathic Accuracy (EA) task functional connectivity data to determine potential predictors (e.g., age, sex, neurocognitive and social cognitive scores) of individual variability. ResultsSSD showed greater MCD during rest (p = 0.00013) and task (p = 0.022). In the hierarchical regression, diagnosis remained significant when social cognition was included during rest (p = 0.008), but not during task (p = 0.50); social cognition was significant during both rest and task (both p = 0.01). ConclusionsDiagnostic differences were more prevalent during unconstrained resting scans, whereas the task pushed participants into a more common pattern which better emphasized transdiagnostic differences in cognitive abilities. Focusing on variability may provide new opportunities for interventions targeting specific cognitive impairments to improve functional outcomes.