Dynamic changes of brain networks during feedback-related processing of reinforcement learning in schizophrenia

Previous studies have reported that schizophrenia (SZ) patients showed selective reinforcement learning deficits and abnormal feedback-related event-related potential (ERP) components. However, how the brain networks and their topological properties evolve over time during transient feedback-related cognition processing in SZ patients has not been investigated so far. In this paper, using publicly available feedback-related ERP data which were recorded from SZ patients and healthy controls (HC) when they performed a reinforcement learning task, we carried out an event-related network analysis where topology of brain functional networks was characterized with some graph measures including clustering coefficient (C), global efficiency (E_global) and local efficiency (E_local) on a millisecond timescale. Our results showed that the brain functional networks displayed rapid rearrangements of topological properties during transient feedback-related cognition process for both two groups. More importantly, we found that SZ patients exhibited significantly reduced theta-band (time window of 170-350 ms after stimuli onset) brain functional connectivity strength, E_global, E_local and C in response to negative feedback stimuli compared to HC group. The network based statistic (NBS) analysis detected one significantly decreased theta-band subnetwork in SZ patients mainly involving in frontal-occipital and temporal-occipital connections compared to HC group. In addition, clozapine treatment seemed to greatly reduce theta-band power and topological measures of brain networks in SZ patients. Finally, the theta-band power, graph measures and functional connectivity were extracted to train a support vector machine classifier for classification of HC from SZ, or Cloz + SZ or Cloz- SZ, and a relatively good classification accuracy of 84.48%, 89.47% and 78.26% was obtained, respectively. The above results suggested a less optimal organization of theta-band brain network in SZ patients, and studying the topological parameters of brain networks evolve over time during transient feedback-related processing could be useful for understanding the pathophysiologic mechanisms underlying reinforcement learning deficits in SZ patients.