Rewriting the valuation and salience of alcohol-related stimuli via memory reconsolidation

Abstract

The transient period of memory instability that can be triggered when memories are retrieved under certain conditions offers an opportunity to modify the maladaptive memories at the heart of substance use disorders (SUDs). However, very well-learned memories (such as those in excessive drinking and alcohol use disorders) are resistant to destabilisation when retrieved or may not destabilise at all. Memory retrieval and intervention procedures that reliably destabilise and update maladaptive motivational memories may help to improve the long-term treatment of SUDs. In 59 hazardous drinkers, we tested a novel retrieval procedure for destabilising well-learned cue-drinking memory networks that maximises prediction error (PE) via guided expectancy violation during retrieval of these memories. This was compared with a retrieval procedure without PE and no-retrieval controls. We subsequently counterconditioned alcohol cues with disgusting tastes and images in all groups and assessed responding to alcohol stimuli 1 week later. Counterconditioning following PE retrieval produced generalised reductions in oculomotor attentional bias, explicit valuation and outcome expectancies in response to alcohol cues 1 week after intervention, evidence of updating of distributed motivational drinking memory networks. These findings demonstrate that well-learned cue-drinking memories can be destabilised and that learning history need not constrain memory destabilisation if PE is maximised at retrieval. Broad rewriting of diverse aspects of maladaptive memory by counterconditioning is achievable following this procedure. The procedure described may provide a platform for the development of novel memory-modifying interventions for SUDs.

Figure 1

Schematic diagram of retrieval/counterconditioning procedure. Counterconditioning is identical for all groups. All groups initially are given a drink and told they will consume it after rating some pictures. In the REACT no PE and REACT+PE groups this is 150 ml beer, in the Control group 150 ml orange juice. Control and REACT no PE consume the drink as expected. In REACT+PE, it is withheld at the last moment. Note the Control group rate the beer images at the beginning of counterconditioning (with no time delay). CS, conditioned stimuli; PE, prediction error; REACT, reactivation.

Figure 2

Reduced liking of alcohol stimuli produced by counterconditioning following MMM reactivation with prediction error. Bars represent mean±s.e.m. A score of five denotes neither liking nor disliking of the stimuli. CS, conditioned stimuli; MMM, maladaptive motivational memory; PE, prediction error.

Figure 3

Abolition of attentional bias at test in REACT+PE group. Attentional bias=dwell time on target image (CSs and novel alcohol cues)—dwell time on matched neutral image. Bars represent mean ±s.e.m. CS, conditioned stimuli; PE, prediction error; REACT, reactivation. Asterisk significant at P<0.05.