Medial prefrontal cortex stimulation accelerates therapy response of exposure therapy in acrophobia

Background: Animal as well as human research indicated that the ventral medial prefrontal cortex (vmPFC) is highly relevant for fear extinction learning. Recently, we showed that targeting the vmPFC with high-frequency repetitive transcranial magnetic stimulation (rTMS) in a placebo-controlled study with 45 healthy controls induced higher prefrontal activity during extinction of conditioned stimuli (CS+) in the active compared to the sham stimulated group and better extinction learning as indicated by ratings, fear potentiated startles and skin conductance responses. Objective: In this study, we aimed to proof our concept of accelerating extinction learning using rTMS of the mPFC in a group of anxiety disorder patients. Methods: To specifically evaluate the impact of rTMS on exposure-based therapy, we applied a sham-controlled protocol over the vmPFC (FPz) succeeded by a virtual reality exposure therapy (VRET) in n = 20 participants with acrophobia and n = 19 controls. Results: We found a significantly higher reduction in active compared to sham stimulated group for anxiety (t[37] = 233, p < 0.05) as well as avoidance ratings t[37] = 2.34, p < 0.05) from pre to post therapy. Conclusion: This study provides first clinical evidence that high-frequency rTMS over the vmPFC improves exposure therapy response of acrophobia symptoms. (C) 2016 Elsevier Inc. All rights reserved.