Impairments in motor-cortical inhibitory networks across recent-onset and chronic schizophrenia: A cross-sectional TMS Study

Abstract

Transcranial magnetic stimulation is an established method to probe inhibitory and facilitatory networks within the human motor cortex. Reduced motor-cortical inhibition is a common finding in schizophrenia patients. Based on neuropathological findings, the reduced cortical inhibition in schizophrenia has been linked mainly to alterations in GABAergic neurotransmission. The aim of this study was to investigate the impact of disease state on intracortical inhibitory and facilitatory networks measured by TMS in schizophrenia. Cortical excitability was investigated in a pooled cross-sectional sample of recent-onset-schizophrenia (RO–SZ), chronically-ill schizophrenia patients (CH–SZ) and healthy controls (HC) using single- and paired-pulse TMS applied to the left primary motor cortex. The sample included 41 RO–SZ, 42 CH–SZ and 59 HC. Analyses were focused on resting motor threshold (RMT), short-interval intracortical inhibition (SICI), intracortical facilitation (ICF) and cortical silent period (CSP). There was a significant difference regarding the mean CSP durations across our three study groups (p=0.002). Subgroup comparisons revealed a shorter CSP in HC compared to RO–SZ (p<0.001). Three group comparisons of SICI (p=0.098) and RMT (p=0.075) showed differences at a trend-level. An overall comparison between HC and all patients showed a significantly reduced SICI (p=0.031) and prolonged CSP (p=0.003) in schizophrenia patients. This is the largest and first cross-sectional investigation of various excitability parameters in schizophrenia patients. These findings indicate general alterations of cortical inhibition, with differences between recent-onset and chronically-ill schizophrenia patients.