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

•High-frequency rTMS (10 Hz) can improve the efficacy of virtual reality exposure based therapy (VRET) in acrophobic patients.•Higher reduction of phobic anxiety and avoidance after VR exposure therapy in the active stimulation group.•R-TMS seems to primarily influence extinction processes and not extinction recall itself.•While the general principle of increased fear extinction after rTMS holds up across species, individual effects may differ.

BackgroundAnimal 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.ObjectiveIn this study, we aimed to proof our concept of accelerating extinction learning using rTMS of the mPFC in a group of anxiety disorder patients.MethodsTo 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.ResultsWe found a significantly higher reduction in active compared to sham stimulated group for anxiety (t[37] = 2.33, p < 0.05) as well as avoidance ratings t[37] = 2.34, p < 0.05) from pre to post therapy.ConclusionThis study provides first clinical evidence that high-frequency rTMS over the vmPFC improves exposure therapy response of acrophobia symptoms.