Variability of dynamic patterns of cortical excitability in schizophrenia: A test-retest TMS-EEG study

Background Altered stimuli processing is a key feature of schizophrenia. Application of concurrent transcranial magnetic stimulation (TMS) with electroencephalography (TMS-EEG) is an effective stimulus which allows direct measurement of the cortical response within a millisecond time resolution. Test-retest TMS-EEG studies present evidence of high reproducibility in healthy controls (HC), however, this stability of response has not been examined in schizophrenia. Objective The current study maps TMS-evoked patterns of cortical excitability in schizophrenia and examine whether these cortical patterns are amenable to change as symptoms of schizophrenia improve. Methods One hundred single-pulse TMS and 100 sham pulses were applied to frontal regions of 19 schizophrenia in-patients and 26 HC while electroencephalography data were simultaneously acquired. Medication and schizophrenia symptoms were reported. This protocol was repeated across three sessions (1 week apart) for each participant. The TMS-evoked cortical response of each participant was averaged and compared between groups. Results Schizophrenia patients showed reduced cortical excitability at early time-windows and increased excitability at later time-windows. Increased excitability at later windows was associated with heightened symptom severity. Schizophrenia patients showed an increased variability in cortical response over sessions relative to HC. Increased change in cortical response from session 1 to session 3 correlated with symptom improvement. Conclusions Schizophrenia patients presented with abnormal patterns of cortical excitability when processing TMS stimuli. These dynamic patterns of cortical response were amenable to change as symptoms of schizophrenia improved. Further research into electrophysiological biomarkers of symptom improvement is hoped to improve current diagnosis and treatment models of schizophrenia. ### Competing Interest Statement The authors have declared no competing interest.