The neural basis of drug stimulus processing and craving: an activation likelihood estimation meta-analysis

The capacity of drug cues to elicit drug-seeking behavior is believed to play a fundamental role in drug dependence; yet the neurofunctional basis of human drug cue-reactivity is not fully understood. We performed a meta-analysis to identify brain regions that are consistently activated by presentation of drug cues. Studies involving treatment-seeking and nontreatment-seeking substance users were contrasted to determine whether there were consistent differences in the neural response to drug cues between these populations. Finally, to assess the neural basis of craving, consistency across studies in brain regions that show correlated activation with craving was assessed.

Appropriate studies, assessing the effect of drug-related cues or manipulations of drug craving in drug-user populations across the whole brain, were obtained via the PubMed database and literature search. Activation likelihood estimation, a method of quantitative meta-analysis that estimates convergence across experiments by modeling the spatial uncertainty of neuroimaging data, was used to identify consistent regions of activation.

Cue-related activation was observed in the ventral striatum (across both subgroups), amygdala (in the treatment-seeking subgroup and overall), and orbitofrontal cortex (in the nontreatment-seeking subgroup and overall) but not insula cortex. Although a different pattern of frontal and temporal lobe activation between the subgroups was observed, these differences were not significant. Finally, right amygdala and left middle frontal gyrus activity were positively associated with craving.

These results substantiate the key neural substrates underlying reactivity to drug cues and drug craving.