Alpha-Synchronized Stimulation of the Dorsolateral Prefrontal Cortex (DLPFC) in Major Depression: A Proof-of-Principle EEG-TMS Study

High-frequency repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex (DLPFC) shows therapeutic potential in pharmaco-resistant patients with major depression. However, clinical efficacy is limited by high inter-individual variability and low response rates. One possible strategy to improve the effect size and consistency may be brain state dependent brain stimulation, i.e. coupling of TMS pulses to the endogenous brain states as reflected by the instantaneous oscillatory brain activity. Here we present findings from a proof-of-principle study of alpha-oscillation synchronized brain stimulation of the frontal cortex in patients with major depression (BOSSFRONT). Repetitive stimulation consistently on the negative peak of ongoing alpha activity in left DLPFC, but not brain state independent intermittent theta-burst stimulation (iTBS), resulted in suppression of resting-state alpha activity in left DLPFC and an increase in TMS-induced beta activity. Findings show that alpha-synchronized rTMS of left DLPFC is both feasible and safe, and suggest that it interferes with frontal brain networks important in the pathophysiology of major depression.