# Modulating explore-exploit biases by improving mood in adults with amphetamine use disorder

> **NIH NIH P20** · LAUREATE INSTITUTE FOR BRAIN RESEARCH · 2024 · $261,706

## Abstract

surging overdose deaths, high likelihood of relapse, and current lack of approved medication to treat the 
disorder. When it comes to decision-making, individuals with MUD often prioritize drug over non-drug rewards 
despite negative life consequences; in addition, they may not sufficiently “explore” all available choices to 
“exploit” the best one (in other words, make the optimal choice leading to positive consequences). Therefore, 
the “explore-exploit” trade-off is often dysfunctional in MUD. Decision-making imbalances in the explore-exploit 
trade-off may extend well into abstinence, a period marked by a negative affective state (low mood, high 
depression and anxiety, withdrawal), which in turn triggers heightened craving and subsequent drug use urges. 
The insula, anterior cingulate cortex and striatum are crucial brain regions involved in explore-exploit behaviors 
and affective state signaling that have also been linked to drug reward processing in MUD. We propose that 
reducing negative affective state (improving mood) could help normalize explore-exploit behaviors and the 
response of these brain areas in individuals currently abstinent from methamphetamine and other drugs. This 
project will use a non-drug-related autobiographical memory recall to improve the mood of individuals with 
MUD and measure whether it normalizes non-drug decision-making, using a functional magnetic resonance 
imaging-based 3-arm bandit task and a behavioral contextual reinforcement learning task. A mixed 
experimental design in n=80 (72 completers, assuming 10% attrition) allows the identification of a between 
subjects 
effect of positive (n=40, 36 completers) vs. neutral (n=40, 36 completers) mood modulation and 
assess the within-subject impact on explore-exploit behaviors pre- versus post-mood modulation. Mood groups 
will be compared on positive and negative affect, and behavioral/brain responses to reward valuation, 
outcomes and learning rates. The overarching goal is to establish that improving mood in individuals with MUD 
can [1] reduce their negative affective state, [2] normalize outcome sensitivity in key brain regions and 
associated learning, and [3] reduce the influence of drug rewards on the valuation of non-drug rewards. This 
approach of this proposal embodies the goals of the NIH RDoC Initiative and the NeuroMAP Center by 
identifying an actionable disease-modifying target (mood) and studying its effect on the cognitive and neural 
dysfunction underlying a specific cognitive process (explore-exploit behaviors) relevant to MUD, and possibly 
other related neuropsychiatric disorders. By targeting the intertwined mechanisms between negative affect and 
explore-exploit biases, innovative, effective intervention strategies for MUD may be unveiled, addressing a 
critical public health challenge.

## Key facts

- **NIH application ID:** 11093606
- **Project number:** 5P20GM121312-07
- **Recipient organization:** LAUREATE INSTITUTE FOR BRAIN RESEARCH
- **Principal Investigator:** Maëlle Camille Marie Gueguen
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $261,706
- **Award type:** 5
- **Project period:** 2024-07-01 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11093606

## Citation

> US National Institutes of Health, RePORTER application 11093606, Modulating explore-exploit biases by improving mood in adults with amphetamine use disorder (5P20GM121312-07). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/11093606. Licensed CC0.

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