Forgetting Alcohol: a Double-blind, Randomized Controlled Trial Investigating Memory Inhibition Training in Young Binge Drinkers.
Phase: NA
Conditions: Binge Drinking
Sponsor: University of Minho

 
1 
Study Protocol 
 
 
 
 
 
 
 
Official Title of the Study:  
Forgetting Alcohol: A Double-blind, Randomized Controlled 
Trial Investigating Memory Inhibition Training in Young Binge 
Drinkers 
 
NCT ID: not yet assigned 
 
Date: February 5, 2019 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
2 
Study Design and Setting 
The present study will be composed of three different phases: 1) behavioral and 
electrophysiological analyses of MI abilities in young BDs as compared to age-matched 
non/low-drinkers; 2) a double-blind, randomized controlled trial (RCT) aiming at 
assessing the effects of a MI training protocol at the behavioral and electrophysiological 
level; and 3) monitoring of self-reported alcohol consumption and alcohol craving 10 
days and 3 months after the MI training. 
 
Target population 
The volunteers will be ninety college students (~50% female), aged between 18 and 23 
years: 45 non/low-drinkers and 45 BDs matched for age and gender. All participants will 
be recruited through a screening questionnaire administered in the classroom of several 
courses taught at the University of Minho (UM). The screening will include the Alcohol 
Use Disorder Identification Test (AUDIT) [1] along with other questions concerning 
alcohol and drugs use.  
 
Inclusion and exclusion criteria 
To participate in the study, college students must meet the following eligibility criteria: 
report (i) drinking 5 or more drinks on one occasion at least once a month, and (ii) 
drinking at a speed of at least two drinks per hour during these episodes (which brings 
blood alcohol concentration to 0.08 gram percent or above [2], in order to be classified as 
BDs; or report (i) never drinking 5 or more drinks on each occasion and (ii) having an 
AUDIT score ≤ 4, to be considered as non/low-drinkers. The students who fulfilled the 
inclusion criteria will perform a clinical interview that will assess the following exclusion 

 
3 
criteria: a) use of illegal drugs except cannabis (as determined by the Drug Use Disorders 
Identification Test-Extended [DUDIT-E], [3]); b) alcohol abuse (i.e., AUDIT ≥ 20); 
consumption of medical drugs with psychoactive effects (e.g., sedatives or anxiolytics) 
during the two weeks before the experiment; c) personal history of psychopathological 
disorders (according to DSM-V criteria); d) history of traumatic brain injury or 
neurological disorder; e) family history of alcoholism or diagnosis of other substance 
abuse; f) occurrence of one or more episodes of loss of consciousness for more than 20 
minutes; g) non-corrected sensory deficits; h) Global Severity Index (GSI) > 90 
(Symptom Checklist-90-Revised questionnaire [SCL-90-R], [4]) or a score above 90 in 
at least two of the symptomatic dimensions.  
 
Quality assurance and randomization  
The protocol will be implemented by three skilled researchers with expertise in 
behavioral and EEG assessments and tDCS interventions. Researchers will not be aware 
of the results of the pre-training EEG assessment and will be blind to the randomization 
procedure that will follow. The randomization of the BD groups will be performed by an 
independent researcher using Microsoft Excel. BDs will receive one of the following 
interventions: 1) Combined training (verum CT and tDCS applied over the right 
dorsolateral prefrontal cortex); 2) Cognitive training (active CT and sham tDCS); or 3) 
Control (sham CT and sham tDCS). Based on this experimental procedure, it is expected 
that researchers will be able to answer the following research questions:  
1. How does BD affect alcohol-related MI in young adults? Namely, are the 
behavioral and electrophysiological MI mechanisms - specifically those related to the 
suppression of alcohol-related memories - altered in BDs when compared to non/low-
drinkers?  

 
4 
2. What is the effect of a MI training on behavioral TNTA task performance? 
Specifically, will the BDs show a reduced recollection of no-think images - mainly for 
alcoholic no-think images – after training?  
3. Are the electrophysiological correlates underlying MI mechanisms and alcohol 
cue reactivity changed by MI training? 
4. Will the MI training reduce alcohol consumption and craving levels at 10-day 
and 3-month follow-ups?  
 
Experimental tasks  
Alcohol Cue Reactivity (ACR) task 
Firstly, the participants will perform the ACR task. In this task, each trial starts 
with a white fixation cross in a grey background for a variable duration ranging from 
1000 to 1500 ms. Subsequently, an alcoholic or non-alcoholic image is randomly 
presented at the center of the screen for 3000 ms. Participants are asked to be focused on 
the fixation cross and then to look at the image whenever it appears. After the 
visualization of each image, participants have to register their emotional responses in 
terms of valence and arousal using the Self-Assessment Manikin [5]. The full task 
includes a total of 80 trials with 40 alcoholic and 40 non-alcoholic images obtained from 
the Amsterdam Beverage Picture Set [6]. This task has the purpose of assessing the 
emotional response and electrophysiological reactivity of participants to alcohol cues. 
 
TNTA task  
 
The TNTA task is a version of the classical Think/No-Think paradigm [7], which 
was specially developed to examine MI mechanisms in alcohol-related contexts [8]. This 
task includes thirty-six pictures (18 related to alcohol and 18 non-related to alcohol) from 

 
5 
the Galician Beverage Picture Set (GBPS) [9] and 36 images of neutral objects obtained 
from the POPORO database [10]. The GBPS is a database of alcohol and non-alcohol 
pictures embedded in real-life scenarios which comprises 6 types of beverages: beer, 
wine, and liquor (alcoholic drinks), and water, juice, and milk (non-alcoholic drinks). The 
TNTA task includes 6 images from each of the 6 beverages. The pictures also differ in 
terms of orientation (vertical or horizontal) and number of people (no people, 1 person, 2 
or more people). As such, within each type of beverage, 3 are vertical (each one with a 
different number of people: 0 people, 1 person, 2 or more people) and the other 3 are 
horizontal (also with 0 people, 1 person, 2 or more people). The task is divided into three 
phases, i.e., 1) the Learning phase, 2) the Think/No-Think (TNT) phase and 3) the 
Memory-Test phase, which are carefully described below.  
 
Learning Phase  
During the Learning phase, participants are asked to memorize 36 image-pairs 
(i.e., a neutral image paired with an image including alcoholic or non-alcoholic drinks) 
divided into three blocks of 12 pairs. Each block starts with the presentation of the 12 
image-pairs at the center of the screen, each for 4000 ms, in a randomized order, and with 
an inter-stimuli interval (ISI) ranging from 1000 to 2000 ms. When the presentation of 
the 12 pairs finished, each of the neutral images are presented for 2000 ms, and the 
participants must try to remember the image that was associated with the neutral object 
through three questions: Q1. “Which beverage was associated with this picture?”; Q2. 
“How was the picture oriented?”; Q3. “How many people were there in the picture?”. In 
each block, the 12 pairs and the questions are repeated three times. At the end of each 
block, feedback with the total number of correct responses will be provided. Correct recall 
will only be considered when participants provide the right answer to the 3 questions. 

 
6 
Thus, the combination of the potential answers to the 3 questions (6 x 2 x 3 = 36) ensured 
that each target image displayed a unique combination. 
 
TNT Phase 
In this phase, there are two possible actions: to Think or to No-Think on the 
alcoholic/non-alcoholic image paired with the neutral object previously. Specifically, in 
the Think condition – determined by a green frame that circumvents the neutral image -, 
participants will be asked to focus on the neutral image and think in the alcoholic/non-
alcoholic image that was associated with it (i.e., the one that was paired with this specific 
neutral image). In the No-Think condition - determined by a red frame that circumvents 
the neutral image -, participants are instructed to focus on the image and to not let the 
previously associated alcoholic/non-alcoholic picture enter their consciousness. All the 
images will be presented for 3000 ms and randomly repeated 10 times and presented for 
four seconds at the center of the screen with an offset-onset ISI ranging from 1100-1300 
ms. From the initial set of 36 neutral images shown in the learning phase only 24 will be 
depicted during the TNT phase, 12 in each condition (i.e., Think vs No Think). The 
remaining 12 neutral images not depicted in this phase will serve as a baseline condition 
for the following Memory-Test phase of the task. 
 
Memory -Test Phase 
During this phase, the 36 neutral images from each pair are again presented, 
including the 12 images of the baseline condition which are not presented during the TNT 
phase. Participants are asked to remember the image (alcoholic or non-alcoholic) that was 
initially associated with the neutral object through the same three questions of the 
Learning phase. Three different versions of the task (where all the pictures were part of 

 
7 
the three conditions: Think, No-Think and baseline) will be created and counterbalanced 
across participants. 
 
TNTA task variations for active and false cognitive training 
Two variations of the TNTA task were developed for the active cognitive training 
and for the false cognitive training. The stimuli employed in these variations of the TNTA 
task were also obtained from the GBPS and POPORO databases; however, these stimuli 
differ from those used in the original TNTA task. The structure of the task for the MI 
active cognitive training is the same as the original TNTA task. However, in this variation, 
the Learning phase is only composed of two blocks of 12-image pairs, and in the TNT 
phase, all the stimuli to be inhibited are alcohol-related images.  
In the false cognitive training version, the Learning phase also have only two 
blocks of 12-image pairs. However, the TNT phase is replaced by a Forced-Choice 
Reaction Time (FCRT) task, during which the participants only must categorize alcoholic 
and non-alcoholic images answering to the question “What type of beverage was there in 
the image?” (answer: “Alcoholic drink” or “Non-alcoholic drink”).  
All the computerized tasks will be programmed in open-source software Psychopy 
[11]. 
 
Procedure  
T1: Clinical Interview 
During this interview, we will verify the fulfillment of the exclusion/inclusion 
criteria and assess the baseline levels of some constructs (e.g., craving levels, 
impulsivity). Consequently, we will use the following instruments: 1) the AUDIT along 
with five additional alcohol use questions (i.e., speed of drinking [number of drinks 

 
8 
consumed per hour], number and type of drinks consumed in a standard week, percentage 
of times getting drunk when going out, age of onset of regular and BD) to assess 
participants’ drinking patterns; 2) the DUDIT-E to examine the consumption of other 
drugs; 3) the Penn Alcohol Craving Scale (PACS) and the Alcohol Craving 
Questionnaire-Short Form Revised (ACQ-SF-R)  to assess the alcohol craving; 4) the 
Barratt Impulsivity Scale-11 (BIS-11) and the short form of the Urgency-Premeditation-
Perseverance-Sensation Seeking-Positive Urgency (UPPS-P) impulsive behavior scale to 
assess participants’ impulsiveness; 5) the Symptom Checklist-90-Revised questionnaire 
(SCL-90-R) to evaluate the presence of psychopathological traits; 6) a clinical history 
interview to explore the personal/family history of psychopathological and neurological 
disorders as well as the overall medical history of the participants; and 7) the Edinburgh 
Handedness Inventory (EHI) to evaluate the participants’ handedness.  
 
T2: Pre-training EEG Assessment 
During the pre-training EEG assessment, psychological (i.e., craving levels), 
behavioral (i.e., alcohol consumption levels and task performance) and neurofunctional 
(e.g., ERPs, brain FC) outcomes will be assessed. EEG data will be collected while 
participants perform the ACR and the TNTA task. Before the EEG recording, participants 
will be asked to perform a breathalyzer test to ensure that blood alcohol concentration 
value is 0.0% (Alcoscan ALC-1). Along with the AUDIT, and in order to determine 
alcohol consumption levels during the previous week and the previous three months, we 
will administer the Alcohol Timeline Followback (TLFB) and the Typical and Atypical 
Drinking Diary (TADD), respectively. After filling in the questionnaires, participants will 
perform the ACR task. Participants’ resting brain activity will be recorded for three 
minutes during eyes-closed prior to the TNTA task. Finally, they will perform the TNTA 

 
9 
task. The total duration of the pre-training EEG assessment will be approximately two 
and a half hours. 
EEG data will be recorded using the ActiveTwo Biosemi System (Biosemi, Inc.) 
from 64 electrodes placed according the 10-10 system [12] and digitized at a 512 Hz rate. 
Vertical and horizontal electrooculogram activity will be recorded to control for eye 
movements and blinks. Two additional electrodes will be placed on the mastoids, 
bilaterally, to provide the signal offline reference. Electrode impedances will be kept 
below 20 kΩ and the EEG signal will be filtered on-line with a 0.01–100 Hz band pass 
filter.  
 
T3: MI Training Sessions 
After the pre-training EEG assessment (T2), BDs will be randomly assigned to 
one of the three training subgroups: a) Combined training; b) Cognitive training; or c) 
Control.  The participants’ allocation to the training group will be done by an independent 
researcher who will be responsible to program the tDCS parameters. Thus, both 
participants and research team will be blind to the randomization procedure. 
During T3, subjects will perform the variation of the TNTA task corresponding to 
the group to which they will be assigned. After the first phase of the task (i.e., Learning 
Phase), neuromodulation (sham or active) will be performed using tDCS - a non-invasive, 
painless and safe brain stimulation method capable of modulating cortical excitability 
through a weak constant electric current induced from two surface electrodes placed on 
the scalp [13]. Twenty minutes of 2 mA direct current will be applied to the scalp using 
a saline-soaked pair of 35 cm2 surface sponge electrodes, through an Eldith DC Stimulator 
Plus (Neuroconn, Germany). To stimulate the right DLPFC, the anodal electrode will be 
placed over F4 according to the 10-20 international system for EEG electrode placement. 

 
10 
The cathode electrode will be placed over the contralateral supraorbital area. During the 
active simulation, the current will fade in for 15 seconds, will be constant at 2 mA for 20 
minutes, and then will fade out for 15 seconds. During the sham stimulation, the electric 
current will fade in during 15 seconds until reaching 2 mA, then will be constant at 2 mA 
for 15 seconds and will fade out for 15 seconds. This procedure makes both active and 
sham stimulation indistinguishable for the participants. Before and after the training 
sessions, participants will answer to a continuous Visual Analog Scale that allows 
checking for possible secondary effects of the electrical stimulation.  
 
T4: Post-training EEG Assessment 
At T4, participants will perform the ACR and TNTA tasks under the same 
procedure to the one undertaken during the T2.  
 
T5: Monitoring of alcohol consumption and alcohol craving.  
Ten days after the post-training EEG assessment, the primary craving and alcohol 
consumption outcomes will be assessed. For this purpose, we will administer the PACS, 
the ACQ-SF-R and the AUDIT. Additionally, three months post-intervention, BDs will 
answer the same questionnaires and also the TADD aiming at assessing medium-term 
effects of the MI training in the alcohol craving and consumption levels.  
 
Management and Ethics 
Ethical requirements for human research will be followed in full accordance with 
the Code of Ethical Principles for Medical Research Involving Humans Subjects outlined 
in the Declaration of Helsinki (64th World Medical Association General Assembly, 
Brazil, 2013). The Ethics Committee for Social and Human Sciences of University of 

 
11 
Minho approved the present protocol in December 12, 2018 (approval reference: CE.CSH 
078/2018). Prior to enrolling in the study, subjects will be informed about the aims, 
conditions and procedure of the study. Two copies of the informed consent forms will be 
provided, both of which will be signed by the researchers and participants. It is 
researchers’ responsibility to guarantee the anonymity of the participants and the 
confidentiality of the data. The files containing data from the participants will be 
identified by the participant’s code, not the name. The document containing the records 
of participants’ personal information (e.g., names, contacts, code) will be stored in a 
different location from the data files and will only be accessible to authorized researchers. 
All files will be password protected and stored by the researchers in secure locations. 
Participants will be able to cease their participation in the study at any time without any 
consequences related to the relationship between the research team, the participant and 
the university. If participants want to terminate their enrollment in the study or ask for 
their data to be deleted later, researchers will promptly erase all data from files and 
eliminate documents using a paper shredder. There are no risks associated to the research 
protocol. College students will receive gift vouchers in order to compensate for their 
participation. 
 
 
References 
1.  Babor TF, Higgins-Biddle JC, Saunders JB, Monteiro MG. Audit. The Alcohol 
Use Disorders Identification Test (AUDIT): guidelines for use in primary care. 
2001. 
2. National Institute of Alcohol Abuse and Alcoholism (2004) NIAAA council 
approves definition of binge drinking. NIAAA Newsletter, 3, p. 3. Available at: 

 
12 
http://pubs.niaaa.nih.gov/publications/Newsletter/winter2004/Newsletter_Numb
er3.pdf 
3. Berman AH, Bergman H, Palmstierna T, Schlyter F. DUDIT. The Drug Use 
Disorders Identification Test–E. MANUAL. Karolinska institutet, Stockholm. 
2007. 
4. Derogatis L. SCL-90 (revised) manual. Baltimore: Johns Hopkins University 
Press. 1983 
5. Bradley MM, Lang PJ. Measuring emotion: the self-assessment manikin and the 
semantic differential. J. Behav. Ther. Exp. Psychiatry. 1994; 25, 49-59. 
https://doi.org/10.1016/0005-7916(94)90063-9 
6. Pronk T, van Deursen, DS, Beraha EM, Larsen H, Wiers RW. Validation of the 
Amsterdam Beverage Picture Set: A controlled picture set for cognitive bias 
measurement and modification paradigms. Alcohol. Clin. Exp. Res. 2015; 39, 
2047-2055. https://doi.org/10.1111/acer.12853 
7. Anderson MC, Green C. Suppressing unwanted memories by executive control. 
Nature. 2001; 410:366-369. doi:10.1038/35066572 
8. López-Caneda E, Carbia C. The Galician Beverage Picture Set (GBPS): A 
standardized database of alcohol and non-alcohol images. Drug Alcohol Depend. 
2018; 184, 42-47. https://doi.org/10.1016/j.drugalcdep.2017.11.022 
9. López-Caneda E, Crego A, Campos AD, González-Villar, A, Sampaio A. The 
Think/No-Think Alcohol Task: A New Paradigm for Assessing Memory 
Suppression in Alcohol-Related Contexts. Alcohol.: Clin. Exp. Res. 2019; 43, 36-
47. https://doi.org/10.1111/acer.13916 

 
13 
10. Kovalenko LY, Chaumon M, Busch NA. A pool of pairs of related objects 
(POPORO) for investigating visual semantic integration: behavioral and 
electrophysiological validation. Brain Topogr. 2012; 25, 272-284. 
11. Peirce JW. PsychoPy—psychophysics software in Python. J. Neurosci. Methods. 
2007; 162, 8-13. https://doi.org/10.1016/j.jneumeth.2006.11.017 
12. Fregni F, Nitsche MA, Loo CK, Brunoni AR, Marangolo P, Leite J, Carvalho S,..., 
Simis M. Regulatory considerations for the clinical and research use of 
transcranial direct current stimulation (tDCS): review and recommendations from 
an 
expert 
panel. 
Clin. 
Res. 
Regul. 
Aff. 
2015; 
32, 
22-35. 
https://doi.org/10.3109/10601333.2015.980944 
13. American Clinical Neurophysiology Society. Guideline 5: Guidelines for standard 
electrode position nomenclature. Am J Electroneurodiagnostic Technol. 2006; 46: 
222–225.