Medial prefrontal cortex stimulation abolishes implicit reactions to threats and prevents the return of fear

Down-regulating emotional overreactions toward threats is fundamental for developing treatments for anxiety and post-traumatic disorders. The prefrontal cortex (PFC) is a critical brain area for downstream modulatory processes, and despite previous studies adopting repetitive Transcranial Magnetic Stimulation (rTMS) over this region provided encouraging results in enhancing extinction processes, no studies have hitherto explored the effects of stimulating the medial PFC (mPFC) on threat memory and generalization. Here we showed that rTMS applied before threat memory retrieval abolishes implicit reactions to learned and new stimuli in humans. These effects were not due to inhibition of overall electrodermal reactivity and enduringly persisted one week later in the absence of rTMS. No effects were detected on explicit recognition patterns. Critically, we observed stronger attenuation of defensive responses in subjects stimulated over the mPFC than over the dorsolateral PFC (dlPFC). Our findings uncover a prefrontal region whose modulation can permanently hamper implicit reactions to learned dangers, representing an advance to long-term deactivating overreactions to threats.