Increasing the Temporal Window in Individuals With Alcohol Use Disorder (RP1A)

National Institute on Alcohol Abuse and Alcoholism (NIAAA), McMaster University, Arizona State University, Carilion Clinic, University of Kentucky

Episodic future thinking (EFT) is based on the new science of prospection, which was first identified in a Science publication in 2007 and refers to pre-experiencing the future by simulation. Considerable evidence suggests that prospection is important for understanding human cognition, affect, motivation, and action. Individuals with damaged frontal areas, as well as individuals with alcohol use disorder (AUD), show deficits in planning prospectively. One systematic method to engender prospection is via EFT. EFT, as applied in our prior studies and in this proposal consists of having participants develop positive plausible future events that correspond to several future time frames (e.g., 2 weeks, 1 month, 3 months etc). For each of these timeframes participants are asked to concretize the events (e.g., What are you doing? Who will be there? What will you see, hear, smell, and feel?). We and others have used EFT to decrease delay discounting (DD) in individuals with AUD and smokers, as well as normal weight, overweight, and obese populations when compared to the control condition, control episodic thinking (CET). Consistent with reinforcer pathology, EFT also reduces alcohol valuation in the purchase task among individuals with AUD. However, no study to date has examined whether EFT reduces alcohol self-administration in the laboratory. Moreover, the neural correlates of EFT in AUD are also unknown. In these studies, we propose to test an intervention, EFT, which we hypothesize will decrease reinforcer pathology measures in a bar-like setting in the laboratory; that is, EFT will decrease delay discounting, as well as alcohol self-administration, demand, and craving compared to a control episodic thinking (CET) condition. Moreover, we hypothesize EFT will enhance activation in brain regions associated with prospection (e.g., hippocampus and amygdala) and the executive decision system (e.g., DLPFC). We will also examine the effect of EFT on real-world drinking.

In study 1, participants will be randomly assigned to experimental or control groups, stratified by AUDIT scores, SES, age and sex. Based on our 8 years of experience recruiting this population, we expect approximately 66% retention among eligible participants. Therefore, we will enroll approximately 107 participants in order to conclude with 64 completers. Participants will complete: a baseline assessment (S1), an alcohol self-administration session (S2 or S3), an fMRI session (S2 or S3). The alcohol self-administration session and the fMRI session will be completed in counterbalanced order. At the beginning of S2 and S3, participants in both groups will be prompted to generate positive events and related cues through a researcher-administered interview-based questionnaire. EFT group participants will be asked to think about and describe the most positive event that could realistically happen at each of 7 delays in the future (1 day, 1 week, 1 month, 3 months, 1 year, 5 years, and 25 years). In contrast, participants randomized to the CET condition, will be asked to think about and describe the most positive event that occurred at each of 7 time points from the recent past (last night from 7pm-10pm, yesterday between 4pm-7pm, yesterday between 1pm-4pm, yesterday from 10am-12pm, yesterday between 7am-10am, the night before last between 7pm-10pm, and evening before last between 4pm-7pm). For each time point, the participant will be asked to integrate the event and sensory information into concise textual and/or auditory cues to be used in subsequent behavioral tasks. Cue generation will occur prior to both self administration and fMRI sessions (S2 and S3) to maximize the relevancy of cues at both sessions. In study 2, participants will complete two sessions and undergo a one-week baseline monitoring phase where they provide breath samples to assess for recent alcohol use and report their drinks per day. Following this baseline period, participants will complete an fMRI then be randomized to either the EFT or Control group. Participants will then complete two weeks of monitoring, where they provide a breath sample three times a day and report the number of drinks they consumed. Participants will then come back to the lab to generate new EFT/CET cues, then complete two more weeks of monitoring. After conclusion of the second intervention period, participants will complete a post intervention session and then a one month follow up one month after study completion.

Delay Discounting, Behavioral Economic Demand, Episodic Future Thinking, Self-Administration, Functional MRI, Alcohol Craving

Participants will generate positive future events they are looking forward to at five time points in the future (1 day, 1 week, 1 month, 3 months, 1 year, 5 years, and 25 years). Participants will be reminded of these events using cues throughout the study and instructed to think about these cues as they make their decisions.

Participants will generate positive recent past events that have happened to them at five time points in the recent past (last night from 7pm-10pm, yesterday between 4pm-7pm, yesterday between 1pm-4pm, yesterday from 10am-12pm, yesterday between 7am-10am, the night before last between 7pm-10pm, and evening before last between 4pm-7pm). Participants will be reminded of these events using cues throughout the study and instructed to think about these cues as they make their decisions.

Delay-discounting tasks provide a measure of the temporal window and examine the devaluation of awards as a function of the delay to the receipt. These computerized assessments provide participants with hypothetical choices between smaller amounts of a reward available immediately and a larger amount of a reward after a range of delays (1 day-25 years). Discounting rates will be measured using adjusting amount delay discounting and minute delay discounting tasks. Change in discounting rates will be compared within-subjects between S1 and S2 AND S1 and S3.

At the first session (S1; baseline measures; Day 1), S2 session (occurs up to 7 days post S1), and S3 (occurs up to 7 days post S2).

Intensity and elasticity of alcohol demand will be determined from an alcohol demand curve via an Alcohol Purchase Task (APT). Change in alcohol demand will be compared within-subjects between S1 and S2 AND S1 and S3.

At the first session (S1; baseline measures; Day 1), S2 session (occurs up to 7 days post S1), and S3 (occurs up to 7 days post S2).

A brief questionnaire (the Alcohol Urges Questionnaire) will be used assess alcohol craving. The Alcohol Urges Questionnaire is an 8-item survey which produces scores between 8-56, where higher scores indicate greater craving. Change in alcohol craving will be compared within-subjects between S1 and S2 AND S1 and S3.

At the first session (S1; baseline measures; Day 1), S2 session (occurs up to 7 days post S1), and S3 (occurs up to 7 days post S2).

The number of alcoholic beverages purchased/consumed during the self-administration session will be recorded. The average number of drinks will be compared between groups.

Self-Administration session will occur at either Session 2 or Session 3 based on counterbalance assignment. S2 occurs up to 7 days post S1 and S3 occurs up to 7 days post S2.

fMRI session will occur at either Session 2 or Session 3 based on counterbalance assignment. S2 occurs up to 7 days post S1 and S3 occurs up to 7 days post S2.

fMRI session will occur at either Session 2 or Session 3 based on counterbalance assignment. S2 occurs up to 7 days post S1 and S3 occurs up to 7 days post S2.

Change in drinks per day and number of positive breath alcohol samples (BrAC) will be compared within-subjects between pre intervention and post intervention. In addition, differences in drinks per day and number of positive BrAC samples will be compared between groups (EFT and CET).

Inclusion Criteria: High-risk or harmful drinking (measured by AUDIT) 21-65 years of age Desire to quit or cut down on their drinking, but do not have proximate plans to enroll in treatment for AUD during the study period Report as one of their top three preferred drinks a beverage appropriate for the alcohol self-administration task (Study 1) Exclusion Criteria: Moderate to severe DSM-5 criteria for substance-use disorders other than alcohol, nicotine, and/or marijuana Current diagnosis of any psychotic disorder History of seizure disorders or traumatic brain injury Contraindication for participation in the self-administration (Study 1) or MRI sessions (Studies 1 and 2) Current pregnancy or lactation.

Investigators will adhere to all NIH requirements regarding data sharing. Participant data collected in this project will be de-identified and made available on a shared secured data repository. We will also share the analysis results. As part of this process, all investigators will be required to agree to the following conditions: 1) will adhere to the reporting responsibilities; 2) will not redistribute the data beyond the requesting individual and named collaborators; 3) will give appropriate acknowledgement; 4) will not use the data for commercial purposes; and 5) will obtain appropriate ethical approvals. Results from research conducted will be shared and disseminated, including: regular project meetings, annual meetings, symposia, workshops, and/or conferences for related groups. Manuscripts will be written and submitted for publication in peer-reviewed journals/conferences, following the NIH Public Access Policy guidelines. All necessary ethical approvals will be obtained.

Data requests will be reviewed by the principal investigator and data will be shared with the expectation of acknowledgment of funding source and primary study team.