A systematic review of TMS and neurophysiological biometrics in patients with schizophrenia

Background: Transcranial magnetic stimulation can be combined with electromyography (TMS-EMG) and electroencephalography (TMS-EEG) to evaluate excitatory and inhibitory functions of the cerebral cortex in a standardised manner. Schizophrenia has been postulated to be a disorder of functional neural connectivity underpinned by relative excitation/inhibition imbalance. The aim of this review is to provide a comprehensive overview of TMS-EMG and -EEG research in schizophrenia focused on excitation/inhibition, connectivity, motor cortical plasticity, and the impact of antipsychotic medications, symptom severity and illness duration on TMS-EMG and -EEG indices.Methods: We searched PsycInfo, Embase and Medline, from inception to April 2020, for studies including TMS outcomes in patients with schizophrenia. The following combination of search terms was used: (transcranial magnetic stimulation OR tms) AND (interneurons OR glutamic acid OR gamma aminobutyric acid OR neural inhibition OR pyramidal neurons OR excita* OR inhibit* OR GABA* OR glutam* OR E-I balance OR excitation-inhibition balance) AND (schizoaffective disorder* OR Schizophrenia OR schizophreni*).Results: TMS-EMG and TMS-EEG measurements revealed deficits in excitation/inhibition, functional connectivity and motor cortical plasticity in schizophrenia. Additionally, increased duration of cortical silent period, a TMS-EMG marker of GABAB receptor activity, by clozapine was a relatively consistent finding.Limitations: Most of the studies used chronic and medicated patients, employed cross-sectional group comparisons and had a small patient sample size. Conclusion: TMS-EMG and TMS-EEG offers an opportunity to develop a novel and improved understanding of the physiological processes underlying schizophrenia and assess the therapeutic effect of antipsychotic medications. In the future, the techniques may also help predict disease progression and further our understanding of the excitatory-inhibitory balance and its implications for mechanisms underlying treatment resistant schizophrenia.