The Neural Basis of Drug Stimulus Processing and Craving: An Activation Likelihood Estimation Meta-Analysis

Abstract

Background 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. Methods 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. Results 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. Conclusions These results substantiate the key neural substrates underlying reactivity to drug cues and drug craving.

Naltrexone ameliorates functional network abnormalities in alcohol‐dependent individuals

“…The medial orbitofrontal cortex and supplementary motor area were particularly implicated as being more segregated. Indeed, AD individuals have reduced volume and cortical thickness of the orbitofrontal cortex (Durazzo et al 2011) that predicts future relapse (Beck et al 2012) and simultaneously show heightened drug cue reactivity in this region (Chase et al 2011; Kuhn & Gallinat 2011; Engelmann et al 2012), which is modulated by gene type during naltrexone (OPRM1 gene G allele carriers) (Kareken et al 2010). Similarly, supplementary motor area volume is reduced in binge drinkers (Kvamme et al 2016), and AD subjects show increased SMA activity related to impulsivity (Claus, Kiehl, & Hutchison 2011).…”

Cocaine Cue-Induced Dopamine Release in Amygdala and Hippocampus: A High-Resolution PET [18F]Fallypride Study in Cocaine Dependent Participants

“…In conjunction with activity in the striatum and hippocampus, these effects influence the ability of motivationally salient stimuli to elicit and sustain focused interest and facilitate the selection of situation appropriate behavioral responses Phillips et al, 2003;Goto and Grace, 2008;Robbins et al, 2008;Shohamy and Adcock, 2010). In humans, the role of the amygdala in the processing of emotionally relevant stimuli has been studied using various methods, including functional neuroimaging (Chase et al, 2011;Tang et al, 2012), assessments of the effects of naturally occurring selective lesions (Adolphs et al, 1995;Tsuchiya et al, 2009), and following direct electrical stimulation (Rayport et al, 2006). Together, these studies Cue-Induced dopamine release in amygdala and hippocampus A Fotros et al are consistent with a more extensive animal literature indicating that the amygdala can modulate associative learning between discrete cues and rewards, influence the emotional intensity attached to events, and regulate striatal responsiveness and its effects on behavioral approach (Savage and Ramos, 2009;Buffalari and See, 2010).…”

“…Several studies have demonstrated that DA transmission facilitates hippocampal synaptic long-term potentiation (Jay, 2003;Li et al, 2003) and likely has an important role in the formation and reactivation of rewardrelated memories (Shohamy and Adcock, 2010;Frey et al, 1990;Otmakhova and Lisman, 1998). In humans, neuroimaging studies have provided evidence of hippocampal activation following exposure to drug cues (Grant et al, 1996;Kilts et al, 2001;Wexler et al, 2001;Chase et al, 2011;Tang et al, 2012). Moreover, activity in dopaminergic midbrain regions evoked by reward anticipation tasks is associated with hippocampal activation and evidence of enhanced hippocampus-dependent long-term memory formation (Wittmann et al, 2005;Adcock et al, 2006).…”

Competing neurobehavioral decision systems and the neuroeconomics of craving in opioid addiction

“…The theoretical background of the cue-reactivity paradigm, however, has several limitations that could be responsible for ineffective translation to treatment findings. 11 The most relevant of these limitations is the dearth of research that integrates advancements from the findings of neuroscience, cognitive psychology, and behavioral economics. The main goal of the present review is to communicate a conceptual and methodological framework of neuroeconomics as it applies to the study of drug craving.…”