Increased Prefrontal Activation During Verbal Fluency Task After Repetitive Transcranial Magnetic Stimulation Treatment in Depression: A Functional Near-Infrared Spectroscopy Study

Background: Previous studies have shown the clinical effect of 2 Hz repetitive transcranial magnetic stimulation (rTMS) for depression; however, its underlying neural mechanisms are poorly understood. The aim of this study was to examine the effects of rTMS on the activity of the prefrontal cortex in patients with depression, using functional near-infrared spectroscopy (fNIRS). Methods: Forty patients with major depressive disorder (MDD) and 40 healthy controls were enrolled in this study. Patients underwent 4 weeks of 2 Hz TMS delivered to the right dorsolateral prefrontal cortex (DLPFC). fNIRS was used to measure the changes in the concentration of oxygenated hemoglobin ([oxy-Hb]) in the prefrontal cortex during a verbal fluency task (VFT) in depressed patients before and after rTMS treatment. The severity of depression was assessed using the Hamilton Rating Scale for Depression-24 item (HAMD-24). Results: Prior to rTMS, depressed patients exhibited significantly smaller [oxy-Hb] values in the bilateral prefrontal cortex during the VFT compared with the healthy controls. After 4 weeks of 2 Hz right DLPFC rTMS treatment, increased [oxy-Hb] values in the bilateral frontopolar prefrontal cortex (FPPFC), ventrolateral prefrontal cortex (VLPFC) and left DLPFC during the VFT were observed in depressed patients. The increased [oxy-Hb] values from baseline to post-treatment in the right VLPFC in depressed patients were positively related to the reduction of HAMD score following rTMS. Conclusion: These findings suggest that the function of the prefrontal cortex in depressed patients was impaired and could be recovered by 2 Hz rTMS. The fNIRS-measured prefrontal activation during a cognitive task is a potential biomarker for monitoring depressed patients’ treatment response to rTMS.