Enhanced theta-gamma coupling associated with hippocampal volume increase following high-frequency left prefrontal repetitive transcranial magnetic stimulation in patients with major depression

The underlying mechanism of repetitive transcranial magnetic stimulation (rTMS) effects on cognition has not been fully examined. Previously, we have reported the left hippocampal volume increase and theta-gamma coupling (TGC) enhancement associated with working memory improvement following rTMS in depression. This study was aimed to examine whether there is a structure-function relationship in hippocampal neuroplasticity induced by prefrontal rTMS. Thirty-one patients with major depression underwent longitudinal MRI scans and resting-state EEG recordings with the 10-20 system using averaged ear-lobes reference, following 10 sessions of high-frequency rTMS over the left dorsolateral prefrontal cortex. Pearson's correlation analyses were applied for the longitudinal changes among the left and right hippocampal volumes as measured by manual volumetry, theta and gamma spectral powers, and TGC as measured by resting-state EEG. The analyses demonstrated that the left hippocampus volume increases correlated with TGC increases at the left central area (r = 0.576, p = 0.001, N = 31), whereas no significant correlations were observed among changes of right hippocampal volume, right central TGC, bilateral gamma or theta powers. These finding suggests structure-function relationship in rTMS-induced neuroplastic changes mediated through the hippocampus and prefrontal network at the stimulated side. Therefore, high-frequency prefrontal rTMS may exert its cognitive effect through the hippocampal structural-functional neuroplasticity.