# The Neurocomputational mechanisms of anhedonia and their role in predicting alcohol use and treatment responsiveness in Veterans with Alcohol Use Disorder"

> **NIH VA I01** · VA SAN DIEGO HEALTHCARE SYSTEM · 2024 · —

## Abstract

Alcohol use disorder (AUD) is highly prevalent in Veterans and is associated with poor treatment
outcomes. Evidence-based treatments (EBTs), such as Cognitive Behavioral Therapy (CBT), show utility in
reducing maladaptive drinking and restoring healthy goals, but more than two thirds of treatment completers
relapse within a year. Anhedonia, i.e., a reduced interest in rewarding activities, is commonly observed in AUD
patients and predicts poorer response to psychiatric treatment. Anhedonic symptoms manifest through a
dopaminergic deficit state in the frontostriatal reward circuitry, which contributes to the reinforcement of alcohol
use as a fast-acting mood-regulating strategy. Moreover, while anhedonia is known to hinder goal-directed
reward behavior, this presentation is multi-faceted, and may impact different reward processing mechanisms,
e.g., learning, anticipating, pursuing, and receiving rewards. However, the degree to which these reward
behavior mechanisms relate to AUD outcomes remains poorly understood and have not been investigated in
Veterans. Understanding these relationships could help shed light on factors that facilitate or hinder AUD
recovery and may help identify specific neurobehavioral targets not adequately addressed in standard care to
guide the development of new interventions. To address these questions, we propose to use computational
modeling and functional neuroimaging to mechanistically characterize the relationships between
anhedonia and drinking behavior in treatment-seeking Veterans with AUD. Computational modeling,
particularly in concert with neuroimaging, provides detailed mechanistic insights into the neurobiology of
cognitive processes, and such methods have been shown to be more accurate in predicting clinical outcomes,
relative to standard behavioral and neuroimaging analysis. We will capitalize on this approach to delineate robust
anhedonia-driven predictors of AUD treatment responsiveness in Veterans.
 A total 124 Veterans with AUD will be recruited through a recently funded clinical trial as they enroll in 12
weeks of group-based CBT (standard care EBT). Participants will further be randomized to an adjunctive
computer-based protocol, i.e., control (sham) or approach-avoidance training (AAT). Because AAT is aimed at
reducing patients’ habitual approach bias towards alcohol cues, it may provide incremental benefits in shifting
approach behaviors from reflexive to more goal-driven. At baseline, 12-, and 24-weeks after treatment onset,
participants will complete a clinical assessment and 2 multi-arm bandit (MAB) tasks (in classic and social
conditions, to be compared in exploratory analyses), in which they must choose on each trial from among a set
of options with unknown reward probabilities, with the goal of maximizing total rewards. Concurrent brain activity
will be measured in a subset of 62 participants. Using Bayesian modeling, we will derive individual parameters
of reward learning (i.e., perceived sta...

## Key facts

- **NIH application ID:** 10799230
- **Project number:** 1I01CX002655-01A1
- **Recipient organization:** VA SAN DIEGO HEALTHCARE SYSTEM
- **Principal Investigator:** Katia Harle
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2024-04-01 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10799230

## Citation

> US National Institutes of Health, RePORTER application 10799230, The Neurocomputational mechanisms of anhedonia and their role in predicting alcohol use and treatment responsiveness in Veterans with Alcohol Use Disorder" (1I01CX002655-01A1). Retrieved via AI Analytics 2026-06-22 from https://api.ai-analytics.org/grant/nih/10799230. Licensed CC0.

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