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

Abstract

A comprehensive understanding of the neurobiology of alcohol cue reactivity is critical to 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 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.

The Effects of Pharmacological Opioid Blockade on Neural Measures of Drug Cue-Reactivity in Humans

“…These latter regions primarily rely on dopamine, GABA, opioid, and glutamate signaling and are implicated in the development of incentive salience (Kalivas and Volkow, 2005). Further, we found that greater tonic subjective methamphetamine craving was associated with greater activation of the precuneus, a region highlighted by multiple meta-analyses to be reliably involved in cue-reactivity for various substances of abuse (Engelmann et al, 2012;Schacht et al, 2013a). Taken together, these results suggest that this novel paradigm is an effective probe of methamphetamine cueinduced craving in individuals with methamphetamine use disorders.…”

“…The increases in self-reported, subjective methamphetamine craving during the presentation of methamphetamine as compared to control cues highlight the initial efficacy of the task in eliciting cue-induced craving. The primary BOLD results depicted greater methamphetamine (vs control) cue-elicited activation in regions that are commonly seen to be cue-reactive for other substances in dependent populations (eg, middle frontal gyrus, ACC, posterior cingulate cortex (PCC)/precuneus, thalamus, insula, inferior occipital cortex, and brain stem) (Engelmann et al, 2012;Schacht et al, 2013a), and in commonly described 'reward'-or 'reinforcement'-related regions (eg, left ventral striatum (NAcc), bilateral dorsal striatum (caudate, putamen), VTA, hippocampus, and amygdala). These latter regions primarily rely on dopamine, GABA, opioid, and glutamate signaling and are implicated in the development of incentive salience (Kalivas and Volkow, 2005).…”

“…The primary aims of the present study were to determine: (1) Whether naltrexone (50 mg) vs placebo moderates blood-oxygen-level dependent (BOLD) measures of methamphetamine cue processing (ie, cuereactivity) and (2) whether naltrexone's effect on methamphetamine cue-reactivity is associated with differential functional connectivity from the striatum and VTA (regions subserving reinforcement-driven behavior) and the precuneus (a region reliably shown to respond to drug cues; Courtney et al, 2014a;Engelmann et al, 2012;Schacht et al, 2013a) to other brain regions, primarily in the cortex, during methamphetamine cue processing, as compared to placebo. Exploratory aims were to test: (1) The effect of naltrexone (50 mg) on cerebral blood flow (CBF) in this sample with methamphetamine use disorder, as naltrexone-induced CBF alterations have been observed in alcohol-dependent populations (Catafau et al, 1999) and represent a potential confound for the analyses of the BOLD fMRI signal, and (2) whether subjective reports of cue-induced methamphetamine craving are related to neural markers of methamphetamine cue processing.…”

Beer Flavor Provokes Striatal Dopamine Release in Male Drinkers: Mediation by Family History of Alcoholism

“…Thus, a large body of literature has examined the human brain structures that respond to such stimuli (for meta-analysis, see Schacht et al, 2012). The taste of an alcoholic beverage is arguably the most proximal conditioned stimulus to the ensuing intoxication.…”

Subjective Responses to Alcohol in the Lab Predict Neural Responses to Alcohol Cues

“…Alcohol cue exposure is the most widely used paradigm in fMRI studies of alcoholism (Schacht et al, 2013) and has been shown to elicit activation in the ventral striatum that correlated with self-reported craving (Wrase et al, 2007). Hence, it represents the ideal task to validate the association between subjective responses to alcohol in the laboratory and neural response to alcohol in the scanner.…”