Investigating cortical excitability and inhibition in patients with schizophrenia: A TMS-EEG study

Background: Transcranial magnetic stimulation (TMS) combined with electromyography (EMG) has widely been used as a non-invasive brain stimulation tool to assess excitation/inhibition (E/I) balance. E/I imbalance is a putative mechanism underlying symptoms in patients with schizophrenia. Combined TMSelectroencephalography (TMS-EEG) provides a detailed examination of cortical excitability to assess the pathophysiology of schizophrenia. This study aimed to investigate differences in TMS-evoked potentials (TEPs), TMSrelated spectral perturbations (TRSP) and intertrial coherence (ITC) between patients with schizophrenia and healthy controls. Materials and methods: TMS was applied over the motor cortex during EEG recording. Differences in TEPs, TRSP and ITC between the patient and healthy subjects were analysed for all electrodes at each time point, by applying multiple independent sample t-tests with a cluster-based permutation analysis to correct for multiple comparisons. Results: Patients demonstrated significantly reduced amplitudes of early and late TEP components compared to healthy controls. Patients also showed a significant reduction of early delta (50 -160 ms) and theta TRSP (30250ms),followed by a reduction in alpha and beta suppression (220 -560 ms; 190 -420 ms). Patients showed a reduction of both early (50 -110 ms) gamma increase and later (180 -230 ms) gamma suppression. Finally, the ITC was significantly lower in patients in the alpha band, from 30 to 260 ms. Conclusion: Our findings support the putative role of impaired GABA -receptor mediated inhibition in schizophrenia impacting excitatory neurotransmission. Further studies can usefully elucidate mechanisms underlying specific symptoms clusters using TMS-EEG biometrics.