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

Abstract

Down-regulating emotional overreactions toward threats is fundamental for developing treatments for anxiety and post-traumatic disorders. The prefrontal cortex (PFC) is critical for top-down modulatory processes, and despite previous studies adopting repetitive Transcranial Magnetic Stimulation (rTMS) over this region provided encouraging results in enhancing extinction, 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 novel stimuli in humans. These effects were not due to inhibition of electrodermal reactivity and enduringly persisted one week later in the absence of rTMS. No effects were detected on explicit recognition. Critically, we observed stronger attenuation of defensive responses in subjects stimulated over the mPFC than the 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.

Adaptive Safety Coding in the Prefrontal Cortex

“…Also supporting a departure from extinctionfocused approaches, recent work showed repetitive transcranial magnetic stimulation (rTMS) modulation of the anterior mPFC inhibited implicit fear reactions to learned threats. 47 This is a departure from emphasis on the dorsolateral PFC as a regulatory hub, which may be limited to extinction paradigms. 48,49 Intriguingly the mPFC is a hub of the brain's Default Mode Network (DMN), which point to safety as an aspect of baseline human cognition.…”

An intracranial dissection of human escape circuits

“…The reactive fear circuit primarily engages when the threat is close to the prey [16], encompassing the periaqueductal gray (PAG) [17, 18], hypothalamus [19], midcingulate cortex (MCC), bed nucleus of the stria terminalis (BNST) [20], and amygdala [21, 22]. Conversely, the cognitive fear circuit [23, 24], involving brain areas such as the ventromedial prefrontal cortex (vmPFC) [25, 26], hippocampus (HPC) [27, 6] and posterior cingulate cortex (PCC), is activated when the threat is not immediate. Except for the brain regions within these two circuits, the striatum and insula also play a crucial role in defensive behavior [28, 29, 30].…”