Motor cortex excitability in schizophrenia or depression and its modulation with prefrontal intermittent theta-burst stimulation

Altered cortical excitability is reported in schizophrenia and depression, but findings are inconsistent. Prefrontal repetitive transcranial magnetic stimulation (TMS) induces short-term motor cortex excitability changes in healthy individuals, but its effect in schizophrenia and depression remains unexplored. Prefrontal intermittent theta burst stimulation (iTBS) improves negative symptoms in depression. Cortical excitability is a suggested biomarker for prefrontal iTBS response. We investigated if prefrontal iTBS affects motor cortex excitability in schizophrenia or depression. Secondary aims were to examine motor cortex excitability as a predictor of iTBS effect on negative symptoms in depression and to compare excitability between groups with schizophrenia, depression and healthy controls. TMS indices of cortical excitability − resting motor threshold, short-interval intracortical inhibition, intracortical facilitation and long-interval intracortical inhibition (LICI) − were pooled from previous studies, including an RCT evaluating iTBS for negative symptoms. The dataset comprised 44 patients with schizophrenia, 52 with depression, and 62 healthy controls. Regression models indicated no effect of active versus sham iTBS on any TMS index (all p ≥ .61). No baseline TMS index predicted negative symptom changes after iTBS in depression (all p ≥ .44). Patients with schizophrenia exhibited more pronounced LICI inhibition than the other groups (Mann-Whitney U = 1670, p < .001). LICI correlated with antipsychotic dose (Spearman's ρ = −0.28, p = .04). Prefrontal iTBS does not modify cortical excitability in schizophrenia or depression, nor does cortical excitability predict prefrontal iTBS effects on negative symptoms. The more pronounced LICI inhibition in schizophrenia may be related to the illness or medication.