Development of transcranial magnetic stimulation for post-traumatic stress disorder therapy : a translational study based on animal model

Abstract

Post-traumatic stress disorder (PTSD) is a chronic detrimental anxiety disorder originated from exaggerate fear memory after a traumatic event. Impaired extinction of fear memory has been hypothesized for a tentative pathophysiology of PTSD based on dysfunction in the medial prefrontal cortex (mPFC) observed in functional neuroimaging studies of PTSD patients. Electrical stimulation of mPFC paired with extinction learning facilitated fear extinction in rats, but not unpaired one. Therefore, transcranial magnetic stimulation (TMS) paired with traumatic reminder was suggested as a potential treatment for PTSD. However, there was no clinical and preclinical study examining the effect of TMS paired with trauma-reminding cue presentation. We examined the effect of 10 Hz repetitive TMS paired with conditioned fear stimulus (CS) in fear memory extinction of rats, and one administered right after or before extinction learning. Only TMS paired with CS reduced fear response compared to sham control on the day of stimulation and the following day. No effect was observed for TMS given several minutes after or before fear extinction. Therefore, TMS paired with traumatic reminder can be a potential treatment for PTSD patients more effective than conventional TMS and exposure therapy. More generally, these results indicate that TMS paired with cognitive intervention such as fear extinction can have specific effect, possibly by transient modulation of neural activity underlying ongoing cognitive process.