Neurobiological Correlates of Cue-reactivity in Alcohol-use Disorders: A Voxel-wise Meta-analysis of FMRI Studies

Altered brain responses to alcohol-associated stimuli are a neural hallmark of alcohol-use disorder (AUD) and a promising target for pharmacotherapy. However, findings in cue-reactivity based functional MRI (fMRI) studies are inconclusive. To investigate the neural substrates of cue-reactivity and their relevance to treatment outcomes, alcohol craving and relapse in AUD patients, we performed five meta-analyses using signed differential mapping software. Our meta-analysis revealed that alcohol cues evoke greater cue-reactivity than neutral cues in the mesocorticolimbic circuit and lower reactivity in the parietal and temporal regions in AUD patients. Compared to controls, AUD individuals displayed hyperactivations in the medial prefrontal cortex and anterior/middle part of the cingulate cortex. After receiving AUD treatment, AUD patients exhibited greater activations in the precentral gyrus but reduced activations in the bilateral caudate nucleus, insula, right DLPFC, and left superior frontal gyrus. No significant results were found in cue-reactivity correlates of alcohol craving and relapse. Our results implicate cue-induced abnormalities in corticostriatal-limbic circuits may underline the pathophysiology of AUD, and have translational value for treatment development.