Title: A Neurosignature of Memory Destabilisation: Developing Tools to Rewrite Food Reward Memories and Treat Overeating Disorders
Funder: The Academy of Medical Sciences

Abstract: Accumulating research into memory reconsolidation indicates that memories can be destabilised following retrieval by brief exposure to retrieval cues. This destabilisation allows direct manipulation/rewriting of memory traces, with lasting effects. For example, I have previously shown disgust counterconditioning to be an effective means to abolish reward-related responses to cues following destabilisation of maladaptive reward memories. In overeating disorders, where learned eating responses to food ‘cues’ are thought to be a central driver of relapse, rewriting maladaptive eating memories in this manner may confer long-term protection against overeating. However, memory destabilisation is currently an unreliable therapeutic target, as it relies upon specific parameters of retrieval, namely retrieval length (formalised as N cue presentations) and prediction error (mismatch between expected and actual reward) being within specific boundaries. The ‘optimal’ and boundary values of these parameters are currently unresolved and no reliable biomarker of memory destabilisation exists, hindering clinical translation. I tackle these key questions, using Pavlovian food reward conditioning as a model. Following conditioning, I will assess retrieval procedures of parametrically varying length and N prediction-errors, prior to disgust counterconditioning of reward cues, using the lasting effects of the latter as a probe to determine the ‘optimal’ retrieval parameters to destabilise memories. I then use machine learning on peri-retrieval EEG activity to derive ‘neurosignatures’ that delineate reward memory destabilisation. This will lay the groundwork to develop a real-time biomarker of reward memory destabilisation, opening up a new generation of highly targeted memory-modifying interventions that rewrite problematic memories for lasting clinical benefit.

Lay abstract: Do you ever suddenly feel hungry and start salivating after smelling your favourite food? If so, it is because through past experience, you have learned to associate that smell with the reward of that delicious food. This kind of reward learning is key for survival; so much so that almost all animals can do it in some form. However, it can also it can be very harmful. For some, these reward associations mean seeing or smelling certain foods can 'trigger’ hunger, uncontrolled overeating and potentially lead to binge-eating disorders. Recent neuroscientific research has shown that a memory process, called reconsolidation, may allow us to overwrite these problematic reward memories. During reconsolidation, recalled memories become briefly unstable, meaning they can be rewritten by relevant new information. For example, it may be possible to unlearn the overwhelming urge to eat in response to trigger cues. This could revolutionise the treatment of binge and overeating disorders. However, there is a key obstacle: whether memories become unstable or not depends on exactly how the memory is retrieved. We currently do not know the best way to destabilise memories, nor whether a memory is unstable or not. With this proposed research, I will test a large range of retrieval techniques to find the best procedures to destabilise chocolate reward memory and use brain-imaging (EEG) to develop a brain-based readout of this destabilisation. This will eventually unlock an ability to reliably destabilise and rewrite problematic reward memories to better treat overeating disorders.

Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS;5.6 PSYCHOLOGICAL AND BEHAVIOURAL
Health categories: MENTAL HEALTH