Neural substrates of smoking cue reactivity: A meta-analysis of fMRI studies

Abstract

Reactivity to smoking-related cues may be an important factor that precipitates relapse in smokers who are trying to quit. The neurobiology of smoking cue reactivity has been investigated in several fMRI studies. We combined the results of these studies using activation likelihood estimation, a meta-analytic technique for fMRI data. Results of the meta-analysis indicated that smoking cues reliably evoke larger fMRI responses than neutral cues in the extended visual system, precuneus, posterior cingulate gyrus, anterior cingulate gyrus, dorsal and medial prefrontal cortex, insula, and dorsal striatum. Subtraction meta-analyses revealed that parts of the extended visual system and dorsal prefrontal cortex are more reliably responsive to smoking cues in deprived smokers than in non-deprived smokers, and that short-duration cues presented in event-related designs produce larger responses in the extended visual system than long-duration cues presented in blocked designs. The areas that were found to be responsive to smoking cues agree with theories of the neurobiology of cue reactivity, with two exceptions. First, there was a reliable cue reactivity effect in the precuneus, which is not typically considered a brain region important to addiction. Second, we found no significant effect in the nucleus accumbens, an area that plays a critical role in addiction, but this effect may have been due to technical difficulties associated with measuring fMRI data in that region. The results of this meta-analysis suggest that the extended visual system should receive more attention in future studies of smoking cue reactivity.

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.…”

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).…”

Hippocampal and Insular Response to Smoking-Related Environments: Neuroimaging Evidence for Drug-Context Effects in Nicotine Dependence

“…Bilateral aHPC and pHPC ROIs were defined following a prior study of aHPC and pHPC connectivity (Chen and Etkin, 2013), taking the anterior-most third and posterior-most third of an HPC ROI consisting of voxels with a 460% likelihood of being in HPC (as defined by the Harvard-Oxford probabilistic structural axis). The following additional ROIs, chosen a priori based on preclinical research (Bossert et al, 2011;Fuchs et al, 2005;McLaughlin and See, 2003;Otis et al, 2014), our previous neuroimaging studies (McClernon et al, 2005(McClernon et al, , 2007(McClernon et al, , 2009) and metaanalysis (Engelmann et al, 2012;Kuhn and Gallinat, 2011;Tang et al, 2012) of cue-reactivity, were created in PickAtlas (Maldjian et al, 2003): (1) ventral striatum (5 mm radius sphere centered on ± 6,4, − 5); (2) amygdala (anatomical); (3) insula (5 mm radius sphere centered on ± 38,10,6); (4) mPFC inclusive of portions of rostral anterior cingulate cortex (5 × 10 × 10 mm box centered on ± 5, 40, 10); and (5) PCC (5 × 5 × 10 mm box centered on ± 5, − 60,20). See Supplementary Figure S3 for visual depictions of the ROIs selected for analyses.…”