Task-related functional magnetic resonance imaging-based neuronavigation for the treatment of depression by individualized repetitive transcranial magnetic stimulation of the visual cortex

To determine whether repetitive transcranial magnetic stimulation(rTMS) of the visual cortex(VC) provides effective and welltolerated treatment and whether magnetic resonance imaging(MRI) measures functional change of the VC as a biomarker of therapeutic effect in major depressive disorder(MDD), we performed a sham-controlled, double-blind, randomized, three-arm VC rTMS treatment study in 74 MDD patients. Neuronavigated rTMS(10 Hz, 90% of resting motor threshold, 1,600 pulses over20 min twice per day) was performed over the VC for five days. Clinical outcome was measured by Hamilton Depression Rating Scale(HAMD-24) at days 0, 1, 3, 5 and after terminating rTMS, with follow-up at four weeks. MRI was measured at days 0 and5. The individualized group exhibited the greatest change in HAMD-24 scores after VC rTMS for 5 days(F=5.53, P=0.005),which were maintained during follow-up period(F=4.22, P=0.016). All patients reported good tolerance. Changes in VC taskrelated functional MRI correlated with symptomatic reduction in the individualized group. Treatment reduced the initially abnormal increase in resting state functional connectivity from the VC to the pre/subgenual anterior cingulate cortex at day 5,especially in the individualized group. We demonstrated therapeutic potential and good tolerance of VC rTMS in MDD patients,indicated by biomarkers of f MRI measurement.