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.

Attentional bias for drug-related stimuli, as measured by emotional Stroop (ES) tasks, is predictive of treatment outcomes for tobacco smoking and other abused drugs. Characterizing relationships between smoking-related attentional bias and brain reactivity to smoking images may help identify neural substrates critical to relapse vulnerability. To this end, we investigated putative relations between interference effects in an offline smoking ES task and functional MRI (fMRI) measures of brain reactivity to smoking versus neutral images in women smokers. Positive correlations were found between attentional bias and reactivity to smoking images in brain areas involved in emotion, memory, interoception, and visual processing including the amygdala, hippocampus, parahippocampal gyrus, insula, and occipital cortex. These findings suggest that smokers with elevated attentional biases to smoking-related stimuli may more readily shift attention away from other external stimuli and toward smoking stimuli-induced internal states and emotional memories. Such attentional shifts may contribute to increased interference by smoking cues, possibly increasing relapse vulnerability. Treatments capable of inhibiting shifts to drug cue-induced memories and internal states may lead to personalized tobacco dependence treatment for smokers with high attentional bias to smoking-related stimuli.