Dissociable memory modulation mechanisms facilitate fear amnesia at different timescales

Memory reactivation renders consolidated memory fragile and preludes memory reconsolidation. However, whether memory retrieval facilitates update mechanisms other than memory reconsolidation remains unclear. We tested this hypothesis in three experiments with healthy human participants. First, we demonstrate that memory reactivation prevents the return of fear shortly after extinction training in contrast to the memory reconsolidation effect which takes several hours to emerge and such a short-term amnesia effect is cue independent (Study 1,N= 57 adults). Furthermore, memory reactivation also triggers fear memory reconsolidation and produces cue-specific amnesia at a longer and separable timescale (Study 2,N= 79 adults). Finally, using continuous theta-burst stimulation (Study 3,N= 75 adults), we directly manipulated brain activities in the dorsolateral prefrontal cortex and found that both memory retrieval and intact prefrontal cortex functions were necessary for the short-term fear amnesia. The temporal scale and cue-specificity results of the short-term fear amnesia are clearly dissociable from the amnesia related to memory reconsolidation, and suggest that memory retrieval and extinction training trigger distinct underlying memory update mechanisms. These findings raise the possibility of concerted memory modulation processes related to memory retrieval and shed light to clinical treatment of persistent maladaptive memory.