Functional neuroimaging studies of alcohol cue reactivity: a quantitative meta-analysis and systematic review

A comprehensive understanding of the neurobiology of alcohol cue reactivity is critical in identifying the neuropathology of alcohol use disorders (AUD) and developing treatments that may attenuate alcohol craving and reduce relapse risk. Functional neuroimaging studies have identified many brain areas in which alcohol cues elicit activation. However, extant studies have included relatively small numbers of cases, with AUD of varying severity, and have employed many different cue paradigms. We used activation likelihood estimation, a quantitative, coordinate-based meta-analytic method, to analyze the brain areas activated by alcohol-related cues across studies, and to examine whether these areas were differentially activated between cases and controls. Secondarily, we reviewed correlations between behavioral measures and cue-elicited activation, as well as treatment effects on such activation. Data analyzed were from 28 studies of 679 cases and 174 controls. Among cases, alcohol cues elicited robust activation of limbic and prefrontal regions, including ventral striatum, anterior cingulate and ventromedial prefrontal cortex. As compared to controls, cases demonstrated greater activation of parietal and temporal regions, including posterior cingulate, precuneus and superior temporal gyrus. Cue-elicited activation of ventral striatum was most frequently correlated with behavioral measures and most frequently reduced by treatment, but these results were often derived from region-of-interest analyses that interrogated only limbic regions. These findings support long-standing theories of mesolimbic involvement in alcohol cue processing, but suggest that cue-elicited activation of other brain areas may more clearly differentiate cases from controls. Prevention and treatment for AUD should consider interventions that may reduce cue-elicited activation of these areas.