Forgetting Alcohol: A Double-Blind, Randomized Controlled Trial Investigating Memory Inhibition Training in Young Binge Drinkers

Abstract

Background: Binge Drinking (BD) has been associated with altered inhibitory control and augmented alcohol-cue reactivity. Memory inhibition (MI), the ability to voluntarily suppress unwanted thoughts/memories, may lead to forgetting of memories in several psychiatric conditions. However, despite its potential clinical implications, no study to date has explored the MI abilities in populations with substance misuse, such as binge drinkers (BDs).

Method: This study-registered in the NIH Clinical Trials Database (ClinicalTrials.gov identifier: NCT05237414)-aims firstly to examine the behavioral and electroencephalographic (EEG) correlates of MI among college BDs. For this purpose, 45 BDs and 45 age-matched non/low-drinkers (50% female) will be assessed by EEG while performing the Think/No-Think Alcohol task, a paradigm that evaluates alcohol-related MI. Additionally, this work aims to evaluate an alcohol-specific MI intervention protocol using cognitive training (CT) and transcranial direct current stimulation (tDCS) while its effects on behavioral and EEG outcomes are assessed. BDs will be randomly assigned to one MI training group: combined [CT and verum tDCS applied over the right dorsolateral prefrontal cortex (DLPFC)], cognitive (CT and sham tDCS), or control (sham CT and sham tDCS). Training will occur in three consecutive days, in three sessions. MI will be re-assessed in BDs through a post-training EEG assessment. Alcohol use and craving will be measured at the first EEG assessment, and both 10-days and 3-months post-training. In addition, behavioral and EEG data will be collected during the performance of an alcohol cue reactivity (ACR) task, which evaluates attentional bias toward alcoholic stimuli, before, and after the MI training sessions.

Discussion: This study protocol will provide the first behavioral and neurofunctional MI assessment in BDs. Along with poor MI abilities, BDs are expected to show alterations in event-related potentials and functional connectivity patterns associated with MI. Results should also demonstrate the effectiveness of the protocol, with BDs exhibiting an improved capacity to suppress alcohol-related memories after both combined and cognitive training, along with a reduction in alcohol use and craving in the short/medium-term. Collectively, these findings might have major implications for the understanding and treatment of alcohol misuse.

Clinical trial registration: [www.ClinicalTrials.gov], identifier [NCT05237414].

Keywords: alcohol; binge drinking; cognitive training; craving; electroencephalograpy (EEG); memory inhibition; randomized controlled trial; transcranial direct current stimulation (tDCS).

FIGURE 1

Flow chart of participants recruitment to the study according to CONSORT guidelines.

FIGURE 2

Graphic representation of the procedure. Participants will perform a clinical interview (T1) to guarantee they fulfill the inclusion criteria and to assess baseline measures (e.g., psychological symptoms and impulsivity). Forty-five college students with a BD pattern will enter the study. To compare BDs with non/low-drinkers, the study will also include a group of 45 aged-matched non/low-drinkers, which will only perform the pre-training EEG assessment. During the pre-training EEG assessment (T2; Monday), alcohol craving and consumption levels will be measured, and participants will perform the TNTA task to assess the behavioral and electrophysiological MI mechanisms. Then (T3), BDs will be randomly distributed for one of three training conditions: Combined Training (i.e., verum tDCS and cognitive training [CT]), Cognitive Training (i.e., sham tDCS and verum CT), and Control (i.e., sham tDCS and sham CT). They will perform three sessions over three consecutive days (i.e., Tuesday, Wednesday, and Thursday). After the training sessions, BDs will perform a post-training EEG assessment (T4; Friday) with a procedure similar to T2. The monitoring of alcohol consumption and alcohol craving (T5) will be conducted 10 days and 3 months after T4. ACQ-SF-R, Alcohol Craving Questionnaire-Short Form Revised; ACR, Alcohol Cue Reactivity task; AUDIT, Alcohol Use Disorder Identification Test; BDs, Binge Drinkers; BIS-11, Barratt Impulsivity Scale-11; CT, cognitive training; DUDIT-E, Drug Use Disorders Identification Test-Extended; EEG, electroencephalogram; Fri, Friday; GSI, Global Severity Index; Mon, Monday; N/LDs, Non/low-drinkers; PACS, Penn Alcohol Craving Scale; SCL-90-R, Symptom Checklist-90-Revised questionnaire; TADD, Typical and Atypical Drinking Diary; TLFB, Alcohol Timeline Followback; Tue, Tuesday; Thu, Thursday; UPPS-P, Urgency, Premeditation, Perseverance, Sensation Seeking, Positive Urgency; Wed, Wednesday.

Overall depiction of the Think/No-Think Alcohol (TNTA) task. (A) During the learning phase, participants will be asked to associate and memorize 36 pairs of neutral objects + alcoholic/non-alcoholic pictures. Then, only the neutral objects will be presented, and participants will have to try to remember the picture (alcoholic/non-alcoholic image) that was associated with this neutral object and answer three questions about the beverage depicted, the orientation of the picture and the number of people present in it. (B) After the learning phase, the Think/No -Think phase will comprehend two conditions: the Think (green square) and the No-Think (light red square). In the Think condition (depicted in the neutral images with a green frame) when participants are presented with the object, they will be instructed to “think of the previously learned alcoholic/non-alcoholic picture and keep it in mind during the entire presentation of the object.” In the No-Think condition (depicted by neutral images with a red frame) they will be asked “not to let the previously associated picture enter your consciousness.” (C) In the memory test phase, the 36 neutral images will be presented again, including the 12 neutral objects of the baseline condition that were not presented in the TNT phase. Participants will be asked to recall—answering the same three questions of the learning phase—the image (alcoholic/non-alcoholic) that was initially associated with the neutral object. Alcohol and non-alcohol images were obtained from Shutterstock (https://www.shutterstock.com) and with the permission of Shutterstock.