Brain-oscillation Synchronised Stimulation of the Prefrontal Cortex: Development and Validation of a Personalized Closed-loop TMS Protocol for the Treatment of Major Depression

Major depressive disorder is a severe psychiatric illness with a lifetime prevalence of about 8-16%. Many patients fail to achieve complete remission of symptoms under antidepressant medication, with about 10% of patients being chronically resistant to several psychopharmacological treatments. Development of alternative non-pharmacological treatments is therefore essential to improve patient care.

Repetitive transcranial magnetic stimulation (rTMS) offers therapeutic potential in this context. Current protocols apply high-frequency rTMS over left dorsolateral prefrontal cortex (DLPFC) to reverse the increased alpha-band oscillatory activity and cortical hypo-excitability in patients with depression. However, translation of rTMS therapy into routine clinical practice has been limited due to low efficacy and high inter-individual variability.

This study aims to optimize rTMS stimulation protocols for MDD by deterministically coupling the timing of TMS to the ongoing oscillatory neural activity in the underlying cortex as measured in real-time with high-density surface EEG. It is hypothesized that alpha phase-locked rTMS of the left DLPFC reverses increased alpha-band oscillatory activity and cortical hypo-excitability more efficiently than current open-loop rTMS protocols used in the treatment of MDD.