Functional magnetic response imaging predictors of alcohol use disorder treatment outcome: a systematic review

BACKGROUND: Despite evidence-based pharmacological and behavioural interventions, alcohol use disorder (AUD) is associated with highly variable treatment outcomes. Functional magnetic resonance imaging (fMRI) may identify neural markers that predict treatment response, ultimately supporting a precision medicine approach to AUD. OBJECTIVES: This systematic review synthesized evidence on fMRI predictors of treatment outcomes in individuals with AUD, evaluated methodological consistency, and identified gaps to guide biomarker development. METHODS: A comprehensive search of PubMed/MEDLINE, Embase, and PsycINFO combined terms related to fMRI, AUD, and treatment outcomes. Eligible studies included participants with AUD receiving pharmacological, behavioural, or neuromodulatory interventions with fMRI measures collected before or early in treatment to predict clinical outcomes. Screening and extraction were conducted in duplicate using Covidence, and study quality was assessed with the Grading of Recommendations Assessment, Development, and Evaluation framework. RESULTS: Of 342 records, 15 studies met the inclusion criteria. Most used alcohol cue reactivity tasks (k = 11), with others using resting-state fMRI (k = 2), a monetary reward task (k = 1), or an alcohol-specific Go/No-Go task (k = 1). Pharmacological treatments were most common (k = 8), followed by behavioural therapies (k = 6) and one neuromodulation trial. Across paradigms, neural activity in the ventral striatum, orbitofrontal cortex, and anterior cingulate cortex commonly predicted outcomes. Greater prefrontal engagement predicted improvement, while heightened striatal cue reactivity predicted relapse. Resting-state findings suggested reduced reward- and stress-network connectivity corresponded with better outcomes. Across studies, however, considerable heterogeneity and inconsistency were present and sample sizes tended to be small. CONCLUSIONS: Evidence implicates frontostriatal and salience circuitry in predicting AUD treatment outcomes, but inconsistency and underpowered studies limit firm conclusions. Larger longitudinal studies are needed to robustly validate clinically useful biomarkers.