The Effect of Transcranial Direct Current and Magnetic Stimulation on Fear Extinction and Return of Fear: A meta-analysis and Systematic Review

Abstract

Anxiety and fear-related disorders are among the most prevalent mental illnesses. Non-invasive brain stimulation methods such as transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS) have been employed to modulate anxiety and fear-related symptoms, but their therapeutic effects remain inconclusive. Pavlovian conditioning and extinction are experimental analogues of exposure therapy that investigate the neural mechanisms of fear extinction and return of fear. We conducted a meta-analysis and qualitative review on the effects of tDCS and TMS on fear extinction and return of fear in non-primate animals and humans. Results show that both anodal and cathodal tDCS over the prefrontal cortex inhibit short-term contextual and cued fear retrieval in animal models. In human studies, anodal tDCS over the medial/ventromedial prefrontal cortex enhances fear extinction, whereas TMS over the dorsolateral/ventromedial prefrontal cortex inhibits return of fear. Our findings suggest the optimal non-invasive brain stimulation protocols for threat extinction in humans.