Multilayer network analysis reveals instability of brain dynamics in untreated first-episode schizophrenia

Although aberrant static functional brain network activity has been reported in schizophrenia, little is known about how the dynamics of neural function are altered in first-episode schizophrenia and are modulated by antipsychotic treatment. The baseline resting-state functional magnetic resonance imaging data were acquired from 122 first-episode drug-naïve schizophrenia patients and 128 healthy controls (HCs), and 44 patients were rescanned after 1-year of antipsychotic treatment. Multilayer network analysis was applied to calculate the network switching rates between brain states. Compared to HCs, schizophrenia patients at baseline showed significantly increased network switching rates. This effect was observed mainly in the sensorimotor (SMN) and dorsal attention networks (DAN), and in temporal and parietal regions at the nodal level. Switching rates were reduced after 1-year of antipsychotic treatment at the global level and in DAN. Switching rates at baseline at the global level and in the inferior parietal lobule were correlated with the treatment-related reduction of negative symptoms. These findings suggest that instability of functional network activity plays an important role in the pathophysiology of acute psychosis in early-stage schizophrenia. The normalization of network stability after antipsychotic medication suggests that this effect may represent a systems-level mechanism for their therapeutic efficacy.