Oscillatory brain state-dependent stimulation with transcranial magnetic stimulation combined with electroencephalography.

Brain oscillations are rapidly fluctuating neural activity carried out by large ensembles of neurons. The responsiveness of the brain to external stimuli and the plasticity induced by external stimulation depend strongly on these oscillatory brain states. Here we detail step-by-step instructions for stimulating the brain by tracking human brain activity via the real-time analysis of brain signals recorded by electroencephalography (EEG) and reconstructed in source space, and timing the application of noninvasive transcranial magnetic stimulation (TMS) in synchronization with oscillatory brain states. Real-time EEG-TMS enables the millisecond-precise timing of TMS pulses relative to target oscillatory brain states, such as the phase of an ongoing oscillation. Initial evidence indicates that oscillatory brain state-dependent EEG-TMS is more effective in inducing long-term plasticity than conventional TMS uncoupled to instantaneous oscillatory brain state. This opens the possibility of personalizing therapeutic brain stimulation by coupling it to specific physiological or pathological brain states. In the procedure, we cover brain MRI and image segmentation for anatomical modeling and accurate source reconstruction of the EEG signals, EEG recording without TMS to validate the origin of the oscillation of interest and to determine its phase targeting accuracy, and the main experiment of oscillatory brain state-dependent real-time EEG-TMS to achieve the desired neuroplastic effect. A moderate level of computer science expertise, standard MRI and TMS neuronavigation equipment and TMS-compatible EEG with an accessible online output copy suffice to perform the protocol. The protocol requires ~10 h to complete.