Opening The Reconsolidation Window to Extinguish Fear Memories: A New Conceptual Approach to Psychotherapeutics
Memory processes occur in several phases. Short-term memory is converted to long-term memory by a process of consolidation that requires the synthesis of new proteins. Transcription factors in the nuclei of hundreds of millions of nerve cells are activated so that specific synapses can be modified for the long term. If protein synthesis is inhibited during a period within a few hours after new learning has occurred, what was learned never gets consolidated and is essentially forgotten. It is thought that this phase of consolidation happens when a memory trace moves from short-term storage in the hippocampus to long-term storage in the cerebral cortex.
Recently a later phase of memory storage called reconsolidation has been identified. When an old memory is recalled, the reconsolidation window opens, and the memory trace becomes temporarily amenable to change. The reconsolidation window (the period during which the trace can be revised) is thought to begin five minutes after a memory is recalled and last for an hour or possibly two. New learning that takes place during the reconsolidation window can be more profound than learning that occurs without recall of the related memory or after the reconsolidation window has closed.
Consider the example of a fearful memory created when a person is attacked in a dark alley. If the person repeatedly visits the same alley without being attacked, they can eventually become less afraid of dark places. Repeated viewing of pictures of dark places can also extinguish the fear. These are typical ways in which a fear memory is extinguished. However, the original fear is subject to spontaneous recovery (the fear of dark places returns without provocation) or to reactivation (if another dangerous situation is encountered, the person may regain their fear of dark alleys).
The new findings suggest that if the extinction process (the repeated exposures to the pictures of the dark alley) takes place during the reconsolidation window after the fear memory of being attacked is recalled, the old fear can be permanently reversed (wiped clean, or re-edited such that it appears forgotten) so that it is no longer subject to spontaneous recovery or reactivation.
Editor’s Note: To accomplish extinction training within the reconsolidation window, first a person must actively recall the old memory, opening the reconsolidation window. Then, after a 5-minute delay, extinction training (e.g. new learning that the old feared place is now safe) should take place within the next hour. This process has been demonstrated in animal studies and is thought to be clinically relevant for humans in the case of phobic anxiety and post-traumatic stress disorder (PTSD). The psychotherapeutic implications of using the reconsolidation window to better ameliorate PTSD fears, avoidance, and flashbacks are enormous.
Observing the Amygdala’s Role in the Extinction of Fear Memory Traces
The amygdala is a crucial part of the learned or conditioned fear pathway. It is activated during fear conditioning and during the recall of cues associated with the fear experience. If the amygdala is removed, conditioning fear does not occur.
A new study published in Science this year by Agren et al. indicates that in humans, the amygdala-based response to conditioned fear can be completely abolished using extinction training within the memory reconsolidation window. Training that took place 10 minutes after the fear memory was activated was successful, while training that took place 6 hours later was not.
On day one of this study, participants were shown a visual cue while receiving a shock 16 times. They began to associate the visual cue with the shock, a process known as fear conditioning.
On day two, the memory of the shock was reactivated by showing the visual cue for two minutes. This was followed by extinction training (presentation of the visual cue without the shock). One experimental group received the extinction training after 10 minutes, i.e. within the memory consolidation window. The other group received the same extinction training 6 hours after seeing the visual cue, when the reconsolidation window had closed.
On day three, participants received a functional magnetic resonance imaging scan (fMRI) while connected to shock electrodes (but not receiving shocks). This revealed activation of the amygdala and related connections in the fear circuit in the 6-hour group. However, the amygdala was not activated in the 10-minute group who had received the extinction training within the reconsolidation window. This suggests that for them, the amygdala-based memory trace was abolished.
On day five, participants received shocks (without the visual cue) and then were re-exposed to the photo. Fear response to the visual cue was measured via skin conductance responses. Participants in the 10-minute extinction group did not show any skin conductance response when they saw the visual cue. The 6-hour group did show skin conductance response to the visual cue, indicating that the fear memory persisted for this group. The 6-hour group also showed significantly greater amygdala activation in response to the visual cue.
Editor’s Note: Fear memories can be updated, revised, or abolished when new learning after active memory recall takes place within but not outside of the reconsolidation window. The fear memory trace that is seen by increased blood flow in the amygdala is abolished, and amygdala fear circuit connectivity with other areas of the brain is attenuated only when extinction training occurs within the reconsolidation window after active memory recall (i.e. 5 minutes to one hour after recall).
Agren et al. conclude: “Reactivated fear memories are sensitive to behavioral disruption…and the amygdala proves to be a key neurobiological substrate for this process [in animals and] also in humans.” Timing new learning within the reconsolidation window is the key to long-term revision of habits and memories.
