Closed-loop phase-locked rTMS treatment decreases global cortical excitability in major depressive disorder patients

Abstract Repetitive transcranial magnetic stimulation (rTMS) has been shown to be an effective treatment for major depressive disorder (MDD). Although considerable clinical data have supported its efficacy, its exact mechanism of action and optimal combination of stimulation parameters remains unclear. Recent research suggests that the delivery of rTMS causes long-term inhibition and excitation of neurons in varied brain areas. Additionally, interest has steadily grown for using neurophysiologic measures of cortical excitability as a biomarker for the outcomes of rTMS treatment of MDD. Under the hypothesis that EEG alpha phase is an index of excitation and inhibition across or within a network, our group developed a novel closed-loop system where an rTMS pulse train can be triggered at a specific phase of each patient's prefrontal EEG alpha rhythm to optimize treatment outcomes. Twenty-four MDD patients were randomly assigned to either the phase synchronized or unsynchronized treatment group at the beginning of treatment. Changes in global mean field power were used to characterize cortical excitability in response to rTMS administration. During the six-week daily rTMS treatment period, we observed that global cortical excitability changes within the quasi-alpha band (6-13 Hz) at rest are related to the treatment outcomes for both groups. Notably, the group received synchronized treatment showed higher decreases in cortical excitability after each session compared to the unsynchronized group. More importantly, within the synchronized treatment group, treatment weeks with a greater decrease in Hamilton Rating Scale for Depression showed significant paired (before vs. after daily treatment) excitability decreases. Our findings provide additional evidence for the hypothesis that changes in excitability are related to the mechanism of action of rTMS, and cortical excitability can serve as a reliable biomarker in rTMS treatment outcomes. Moreover, our closed-loop phase-locking rTMS delivery system can induce reduction in excitability, and thus might help increase treatment efficacy. Research Category and Technology and Methods Clinical Research: 10. Transcranial Magnetic Stimulation (TMS) Keywords: rTMS, MDD, EEG-synchronization, cortical excitability