Novel method for identification of individualized resonant frequencies for treatment of Major Depressive Disorder (MDD) using repetitive Transcranial Magnetic Stimulation (rTMS): A proof-of-concept study.

BACKGROUND: Repetitive Transcranial Magnetic Stimulation (rTMS) is an effective treatment for Major Depressive Disorder (MDD), but therapeutic benefit is highly variable. Clinical improvement is related to changes in brain circuits, which have preferred resonant frequencies (RFs) and vary across individuals. OBJECTIVE: We developed a novel rTMS-electroencephalography (rTMS-EEG) interrogation paradigm to identify RFs using the association of power/connectivity measures with symptom severity and treatment outcome. METHODS: 35 subjects underwent rTMS interrogation at 71 frequencies ranging from 3 to 17 Hz administered to left dorsolateral prefrontal cortex (DLPFC). rTMS-EEG was used to assess resonance in oscillatory power/connectivity changes (phase coherence [PC], envelope correlation [EC], and spectral correlation coefficient [SCC]) after each frequency. Multiple regression was used to detect relationships between 10 Hz resonance and baseline symptoms as well as clinical improvement after 10 sessions of 10 Hz rTMS treatment. RESULTS: Baseline symptom severity was significantly associated with SCC resonance in left sensorimotor (SM; p < 0.0004), PC resonance in fronto-parietal (p = 0.001), and EC resonance in centro-posterior channels (p = 0.002). Subjects significantly improved with 10 sessions of rTMS treatment. Only decreased SCC SM resonance was significantly associated with clinical improvement (r = 0.35, p = 0.04). Subjects for whom 10 Hz SM SCC was highly ranked as an RF among all stimulation frequencies had better outcomes from 10 Hz treatment. CONCLUSIONS: Resonance of 10 Hz stimulation measured using SCC correlated with both symptom severity and improvement with 10 Hz rTMS treatment. Research should determine whether this interrogation paradigm can identify individualized rTMS treatment frequencies.