Real-time TMS-EEG for brain state-controlled research and precision treatment: a narrative review and guide

Transcranial magnetic stimulation (TMS) modulates neuronal activity, but the efficacy of an open-loop approach is limited due to the brain state’s dynamic nature. Real-time integration with electroencephalography (EEG) increases experimental reliability and offers personalized neuromodulation therapy by using immediate brain states as biomarkers. Here, we review brain state-controlled TMS-EEG studies since the first publication several years ago. A summary of experiments on the sensorimotor mu rhythm (8–13 Hz) shows increased cortical excitability due to TMS pulse at the trough and decreased excitability at the peak of the oscillation. Pre-TMS pulse mu power also affects excitability. Further, there is emerging evidence that the oscillation phase in theta and beta frequency bands modulates neural excitability. Here, we provide a guide for real-time TMS-EEG application and discuss experimental and technical considerations. We consider the effects of hardware choice, signal quality, spatial and temporal filtering, and neural characteristics of the targeted brain oscillation. Finally, we speculate on how closed-loop TMS-EEG potentially could improve the treatment of neurological and mental disorders such as depression, Alzheimer’s, Parkinson’s, schizophrenia, and stroke.