Brain Reactivity to Smoking Cues Prior to Smoking Cessation Predicts Ability to Maintain Tobacco Abstinence

Abstract

Background Developing means to identify smokers at high risk for relapse could advance relapse prevention therapy. We hypothesized that functional magnetic resonance imaging (fMRI) reactivity to smoking-related cues, measured prior to a quit attempt, could identify smokers with heightened relapse vulnerability. Methods Twenty-one nicotine-dependent women underwent fMRI prior to quitting smoking, during which smoking-related and neutral images were shown. These smokers also were tested for possible attentional biases to smoking-related words using a computerized emotional Stroop (ES) task previously found to predict relapse. Smokers then made a quit attempt and were grouped based on outcomes (abstinence versus slip: smoking 1 cigarette after attaining abstinence). Pre-quit fMRI and ES measurements in these groups were compared. Results Slip subjects had heightened fMRI reactivity to smoking-related images in brain regions implicated in emotion, interoceptive awareness, and motor planning and execution. Smoking cue-induced insula and dorsal anterior cingulate cortex (dACC) reactivity correlated with an attentional bias to smoking-related words. A discriminant analysis of ES and fMRI data predicted outcomes with 79% accuracy. Additionally, smokers who slipped had decreased fMRI functional connectivity between an insula-containing network and brain regions involved in cognitive control, including the dACC and dorsal lateral prefrontal cortex, possibly reflecting reduced top-down control of smoking-related cue-induced emotions. Conclusions These findings suggest that the insula and dACC are important substrates of smoking relapse vulnerability. The data also suggest that relapse-vulnerable smokers can be identified prior to quit attempts, which could enable personalized treatment, improve tobacco-dependence treatment outcomes, and reduce smoking-related morbidity and mortality.

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

“…In both left and right INS, PSEs resulted in less deactivation than PNEs, an effect that was not observed for standard environments and proximal cues. The INS has been proposed as a critical substrate of tobacco use: smokers with insula damage exhibit increased likelihood of quitting smoking Naqvi et al, 2007); selfreported craving (Kuhn and Gallinat, 2011;Tang et al, 2012) and cessation outcomes (Janes et al, 2010) are correlated with insula reactivity to proximal smoking cues; and inactivation of insula decreases proximal cue-provoked nicotine seeking in rodents (Forget et al, 2010;Pushparaj et al, 2013). Less is known about the role of the insula in contextual drug effects; however, in a recent study, insula inactivation in rats led to disruption of amphetamine CPP (Contreras et al, 2012).…”

Striatal Morphology is Associated with Tobacco Cigarette Craving

“…The ventral anterior putamen not only is larger in occasional stimulant users (Mackey et al, 2014), but this striatal subregion receives projections from the insula (Chikama et al, 1997), a brain region implicated in maintaining nicotine dependence (Naqvi et al, 2007) and smoking cue-reactivity (Janes et al, 2010). The insula and striatum may interact to mediate nicotine dependence, as damage to both of these brain regions disrupts smoking (Gaznick et al, 2014), and suggests a possible link between ventral anterior putamen deformations and cue-reactivity due to striatal-insula interactions.…”

Food and Drug Reward: Overlapping Circuits in Human Obesity and Addiction

“…Accordingly, the reactivity of this brain region has been suggested to serve as a biomarker to help predict relapse (Janes et al 2010).…”