Bidirectional connectivity alterations in schizophrenia: a multivariate, machine-learning approach

Objective: It is well known that altered functional connectivity is a robust neuroimaging marker of schizophrenia. However, there is inconsistency in the direction of alterations, i.e., increased or decreased connectivity. In this study, we aimed to determine the direction of the connectivity alteration associated with schizophrenia using a multivariate, data-driven approach. Methods: Resting-state functional magnetic resonance imaging data were acquired from 109 individuals with schizophrenia and 120 controls across two openly available datasets. A whole-brain resting-state functional connectivity (rsFC) matrix was computed for each individual. A modified connectome-based predictive model (CPM) with a support vector machine (SVM) was used to classify patients and controls. We conducted a series of multivariate classification analyses using three different feature sets, increased, decreased, and both increased and decreased rsFC. Results: For both datasets, combining information from both increased and decreased rsFC substantially improved prediction accuracy (Dataset 1: accuracy = 70.2%, permutation p = 0.001; Dataset 2: accuracy = 64.4%, permutation p = 0.003). When tested across datasets, the prediction model using decreased rsFC performed best. The identified predictive features of decreased rsFC were distributed mostly in the motor network for both datasets. Conclusion: These findings suggest that bidirectional alterations in rsFC are distributed in schizophrenia patients, with the pattern of decreased rsFC being more similar across different populations.