Impaired Control Symptoms in Alcohol Use Disorder Show Convergent Associations Across Behavioral and Neural Markers of Inhibitory Control and Drinking Behavior

Abstract

Background: Deficits in inhibitory control are considered a central feature of alcohol use disorder (AUD), yet behavioral and neuroimaging findings have been inconsistent. One potential explanation is the marked heterogeneity of AUD, which encompasses multiple symptom dimensions that may differ in their underlying neurocognitive mechanisms. In this study, we investigated whether behavioral and neural markers of inhibitory control are associated with specific DSM-5 AUD symptom domains. Methods: A total of 589 participants (432 with non-treatment seeking AUD, 157 controls) completed a Stop-Signal Task (SST) during fMRI. Associations between DSM-5 symptom domains (impaired control over alcohol use, risky use, social problems, physical dependence) and SST performance, inhibition-related brain activation, and alcohol consumption were examined. Real-life drinking behavior was additionally assessed over 12 months using ecological momentary assessment (EMA). Results: Greater impaired control symptom severity was associated with poorer performance on go trials and diminished post-error slowing during SST. At the neural level, higher impaired control symptom severity was associated with reduced activation across fronto-insular, parietal, cingulate, supplementary motor, and cerebellar regions. In contrast, other symptom domains showed little to no associations with inhibition-related behavioral or neural measures. Higher impaired control symptom severity was associated with greater alcohol consumption across questionnaire-based and EMA-based assessments. Conclusions: In this large cohort, altered behavioral performance and recruitment of inhibition-related brain regions in the SST was selectively linked to impaired control symptoms. These findings highlight the importance of symptom-based approaches for understanding heterogeneity in addiction and may inform the development of more targeted interventions.