Report

Teaser, summary, work performed and final results

Periodic Reporting for period 2 - WipeOutFear (How the Brain Learns to Forget - The Neural Signature of Fear Memory Erasure)

Teaser

Targeted pharmacological or behavioural interventions applied at the time of retrieval of an emotional memory can persistently block its later expression, perhaps due to memory erasure. The possibility to block the expression of targeted emotional memories carries enormous...

Summary

Targeted pharmacological or behavioural interventions applied at the time of retrieval of an emotional memory can persistently block its later expression, perhaps due to memory erasure. The possibility to block the expression of targeted emotional memories carries enormous potential for the treatment of emotional memory disorders such as anxiety, depression, PTSD and addiction. In the current project, we explore the nature of such post-retrieval amnesia and the conditions under which it occurs. In particular, we want to uncover whether post-retrieval amnesia reflects memory erasure (a storage or retention deficit) or an impairment to retrieve an otherwise intact memory trace (an expression or retrieval deficit), develop new techniques to block the expression of emotional meories, and reveal under which circumstances memories become sensitive to such amnestic interventions.

Work performed

The main activities and major achievements of the project so far are as follows:

In one series of experiments, we extensively demonstrated that the induction of post-retrieval amnesia using either pharmacological interventions (administration of amnestic drugs) or behavioural interventions (administration of extinction training) is less replicable than existing reports would suggest, in rats as well as in humans.

In another series of experiments, conducted in collaboration with researchers in Argentina, we demonstrated that similar conditions govern both the sensitivity of retrieved emotional memories to pharmacological interventions (administration of amnestic drugs) and to behavioural interventions (administration of extinction training) for inducing amnesia.

In further work, we demonstrated that pharmacologically induced amnesia does not readily transfer beyond the retrieval cues used to reactivate the memory prior to the pharmacological intervention. This poses a major challenge for the main storage deficit theory (the reconsolidation blockade account) as well as for the main retrieval deficit theory (the memory integration account) of post-retrieval amnesia. Our results also imply important limitations for the clinical application of post-retrieval amnesia alluded to above.

Finally, in yet another series of experiments, we have explored a number of alternative ways to durably block the expression of emotional memories in humans and rats, some of which have yielded very promising results that we are currently following up.

Final results

Our finding that prediction error governs the sensitivity of retrieved memories not only to pharmacological but also to behavioural amnestic interventions helps to clarify the inconsistent replicability of previous findings.

Our observations regarding the lack of transfer of post-retrieval amnesia to cues not present during memory retrieval will force a new conceptualization of the nature of apparent memory erasure.

Our findings that emotional memory expression can be attenuated through approaches that are fundamentally different from existing approaches, in humans and rats, shed new light on the mechanisms of and conditions for memory suppression and bear promise for the development of novel clinical interventions that circumvent fundamental problems of current approaches.

Website & more info

More info: http://ppw.kuleuven.be/wipeoutfear.