Neural correlates of alcohol use disorder severity among nontreatment-seeking heavy drinkers: An examination of the incentive salience and negative emotionality domains of the alcohol and addiction research domain criteria

Background: The Alcohol and Addiction Research Domain Criteria (AARDoC) propose that alcohol use disorder is associated with neural dysfunction in three primary domains: incentive salience, negative emotionality, and executive function. Prior studies in heavy drinking samples have examined brain activation changes associated with alcohol and negative affect cues, representing the incentive salience and negative emotionality domains, respectively. Yet studies examining such cue-induced changes in functional connectivity (FC) are relatively sparse. Methods: Nontreatment-seeking heavy drinking adults (N = 149, 56.0% male, 48.6% non-white, mean age 34.8 years (SD = 10.0)) underwent functional magnetic resonance imaging during presentation of alcohol, negative, and neutral pictures. We focused on FC changes involving the nucleus accumbens and amygdala in addition to activation and FC correlations with self-reported AUD severity. Results: For alcohol cues versus neutral cues, we observed accumbens FC changes in the cerebellum and prefrontal cortex (PFC), and amygdala FC changes with occipital, parietal, and hippocampal regions. AUD severity correlated positively with activation in the cerebellum (p < 0.05), accumbens FC in the cingulate gyri, somatosensory gyri, and cerebellum (p < 0.05), and with amygdala FC in the PFC and inferior parietal lobule (p < 0.05) for alcohol cues versus neutral cues. For negative cues versus neutral cues, we observed accumbens FC changes in the lateral temporal, occipital, and parietal regions, and amygdala FC changes in the fusiform and lingual gyri (p < 0.05). Conclusions: The present findings provide empirical support for the AARDoC domains of incentive salience and negative emotionality and indicate that AUD severity is associated with salience and response control for reward cues. When covarying for differences in nonalcohol substance use and mood disorder diagnoses, AUD severity was also associated with emotional reactivity for negative cues.