'Cut the roots': rTMS reveals the crucial role of prefrontal cortex in threat memory consolidation in humans

Abstract It is unclear how the brain consolidates aversive memories and whether this process can be disrupted. We hypothesized that targeting the dorsolateral prefrontal cortex (dlPFC) within the consolidation time window by repetitive transcranial magnetic stimulation (rTMS) could block the encoding of a threat memory, disclosing the crucial involvement of this brain region in consolidation. To this aim, fifty-four healthy participants took part in a two-days threat conditioning paradigm. On the first day, participants underwent an acquisition phase. Immediately after, in different groups, an inhibitory rTMS protocol was applied to the dlPFC, or over an occipital control site or as sham. Subsequently, a threat memory recall was performed to test the effect of the rTMS on the consolidation of the previously acquired threat memory. The same procedure occurred after 1 hour to assess rTMS effect outside its inhibitory window, and 24 hours later to test the stability of the offline effects of the rTMS. The results suggested that all groups correctly acquired the threat conditioning, and no differences between groups were observed. The control groups showed memory recall across the three sessions after rTMS, while, critically, the dlPFC group did not recall threat responses in any of the three recall phases. We provide causal evidence that selectively targeting the dlPFC within the consolidation time window prevents the return of threat. Furthermore, memory disruption lasted longer than the inhibitory time window of the rTMS. This effect reveals that we have not only affected the dlPFC activations, but we have hampered the underlying time-locked consolidation process. Together with our previous findings targeting the reconsolidation process, the present results provide new evidence for future clinic applications aiming at interfering with the consolidation and the reconsolidation of traumatic memories. Research Category and Technology and Methods Basic Research: 10. Transcranial Magnetic Stimulation (TMS) Keywords: Threat conditioning, Repetitive transcranial magnetic stimulation, Consolidation, Dorsolateral Prefrontal Cortex