A Prediction Error-driven Retrieval Procedure for Destabilizing and Rewriting Maladaptive Reward Memories in Hazardous Drinkers

The overall goal of this behavioral memory retrieval procedure is to reactivate and destabilize maladaptive reward memories pertaining to drinking in heavy beer drinkers. The procedure aims to open the memory reconsolidation window to allow the testing of subsequent interventions. This method can help answer key questions in the memory reconsolidation field, such as what is the role of prediction error in destabilizing naturalistic alcohol memories, and what procedures following memory destabilization are most effective for targeting maladaptive reward memories.

The main advantage of this technique is that it appears to allow destabilization of highly entrenched alcohol memories despite a lack of information about the learning history of those memories. This allows us to assess subsequent interventions within the reconsolidation window. This technique may allow us to develop effective reconsolidation-based therapies for alcohol use disorders, as it appears to circumvent a key obstacle in the field.

In particular, it allows us to destabilize an entrenched maladaptive memory without knowledge of the learning history. Begin by using a micropipette to add 80 microliters of denatonium benzoate solution into a mixing glass. Use a graduated cylinder to carefully measure 120 milliliters of clean water into the mixing glass containing the denatonium benzoate solution.

Stir well to mix, then evenly divide the 0.067%denatonium benzoate solution into eight clean, identical opaque cups. Lastly, to prepare for the participant, arrange the eight cups of bitter drink behind a screen such that they are easily reached by the experimenter but will be out of sight of the participant. For participants in the retrieval plus PE and retrieval no PE groups, pour 150 milliliters of chilled alcohol-free beer into a half-pint glass and place this on the table between the participant and the display screen.

Note, for those in the no retrieval PE group, pour 150 milliliters of chilled orange juice into the glass and place this on the table in front of the participant. Then, present instructions about this stimulus-rating procedure. Show examples of the on-screen instructions that the participant will see when they are required to consume the drink in front of them.

Instruct the participant to drink only when the green text drink now is presented. Then, using the software begin the reactivation task in which images are presented one at a time for 10 seconds each in pseudo-randomized order. Finally, record the participants pleasantness urge ratings in response to four beer or orange juice cues depending on the group and two neutral cues.

After all images have been rated, direct the participants attention to the drink in front of them. Then present the first two screens that read pick up drink and prepare to drink, respectively, for five seconds each. Then for those in retrieval PE and no retrieval PE groups present the final screen that reads stop do not drink.

Note, for those in the retrieval no PE group, present the final screen that reads drink now for five seconds and have the participant consume the beer. Then, after consuming or not consuming the drink, show the screen that reads put down the drink and press the space bar to continue. Remove the glass from the sight of the participants.

Finally, have the participants rate out loud how expected or unexpected the preceding instructions were from minus five, completely unexpected, to five, completely expected, and write down the response. Immediately prior to starting the counter-conditioning task, have the participant in the no retrieval PE group rate the four beer CS for pleasantness once. Then, once the participant understands that they are required to make two ratings per trial, one for the initial picture and one for the outcome, begin the counter-conditioning task by pressing the space bar.

Take the first UCS drink from behind the screen and place this in front of the participant in preparation for the drink now instructions. Present the first CS image in the sequence for six seconds. Have the participant rate how pleasant they find the image within the six seconds, from extremely unpleasant to extremely pleasant, using marked number keys on the keyboard.

Then, present the drink now instructions for six seconds and have the participant pick up the cup and consume the liquid. After they have consumed the entire 15 milliliters, have the participant rate the pleasantness of the gustatory UCS outcome on the same minus five to plus five scale using the response keys. Remove the empty cup and replace with the next 15 milliliter cup of denatonium benzoate solution.

Present the next CS in the sequence, a neutral image, for six seconds and have the participant rate how pleasant they find the image within this period using the response keys. Complete the remaining 22 trials. Finally, after all 24 trials have been completed, provide the participant with two squares of milk chocolate to remove the residual bitter taste of the denatonium benzoate solution.

Before counter-conditioning, pleasantness ratings of beer and neutral CS images did not differ at baseline. However, they diverged over trials of counter-conditioning with pleasantness ratings for reinforced beer images reducing significantly through repeated pairing with the pictorial and bitter drink UCS’s. In the retrieval prediction error group, reduced pleasantness ratings were evident in response to beer CS images used in the counter-conditioning task, as well as to novel beer and wine images rated for the first time at follow-up.

Once mastered, this technique can be completed in a few minutes if it is performed properly. While attempting this procedure, it’s important to remember that participants must expect to be able to drink the drink that they’re given. Following this procedure, various memory-targeting methods like extinction, counter-conditioning, or drug intervention can be performed to assess their efficacy in weakening or updating maladaptive reward memories.

After watching this video, you should have a good understanding of how to use a memory-retrieval and prediction error procedure to attempt to destabilize maladaptive reward memories. Don’t forget that working with hazardous drinkers requires care and proper ethical approval, and this procedure should always be carried out in a setting that puts participants safety and comfort first.