Altered nonlinear Granger causality interactions in the large-scale brain networks of patients with schizophrenia

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Objective. It has been demonstrated that schizophrenia (SZ) is characterized by functional dysconnectivity involving extensive brain networks. However, the majority of previous studies utilizing resting-state functional magnetic resonance imaging (fMRI) to infer abnormal functional connectivity (FC) in patients with SZ have focused on the linear correlation that one brain region may influence another, ignoring the inherently nonlinear properties of fMRI signals. Approach. In this paper, we present a neural Granger causality (NGC) technique for examining the changes in SZ’s nonlinear causal couplings. We develop static and dynamic NGC-based analyses of large-scale brain networks at several network levels, estimating complicated temporal and causal relationships in SZ patients. Main results. We find that the NGC-based FC matrices can detect large and significant differences between the SZ and healthy control groups at both the regional and subnetwork scales. These differences are persistent and significantly overlapped at various network sparsities regardless of whether the brain networks were built using static or dynamic techniques. In addition, compared to controls, patients with SZ exhibited extensive NGC confusion patterns throughout the entire brain. Significance. These findings imply that the NGC-based FCs may be a useful method for quantifying the abnormalities in the causal influences of patients with SZ, hence shedding fresh light on the pathophysiology of this disorder.