Excitation/inhibition imbalance in schizophrenia: a meta-analysis of inhibitory and excitatory TMS-EMG paradigms

Abstract Cortical excitation-inhibition (E/I) imbalance is a potential model for the pathophysiology of schizophrenia. Previous research using transcranial magnetic stimulation (TMS) and electromyography (EMG) has suggested inhibitory deficits in schizophrenia. In this meta-analysis we assessed the reliability and clinical potential of TMS-EMG paradigms in schizophrenia following the methodological recommendations of the PRISMA guideline and the Cochrane Handbook. The search was conducted in three databases in November 2022. Included articles reported Short-Interval Intracortical Inhibition (SICI), Intracortical Facilitation (ICF), Long-Interval Intracortical Inhibition (LICI) and Cortical Silent Period (CSP) in patients with schizophrenia and healthy controls. Meta-analyses were conducted using a random-effects model. Subgroup analysis and meta-regressions were used to assess heterogeneity. Results of 36 studies revealed a robust inhibitory deficit in schizophrenia with a significant decrease in SICI (Cohen’s d: 0.62). A trend-level association was found between SICI and antipsychotic medication. Our findings support the E/I imbalance hypothesis in schizophrenia and suggest that SICI may be a potential pathophysiological characteristic of the disorder.