Neural cue reactivity during acute abstinence predicts short-term smoking relapse

Abstract

In smokers, neural responses to smoking cues can be sensitive to acute abstinence, but the degree to which abstinence-related cue reactivity contributes to relapse is not fully understood. This study addressed this question in a sample of 75 smokers who were motivated to quit smoking. Participants underwent blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) during presentation of visual smoking cues and neutral stimuli on two occasions: once during smoking satiety and once following 24-hour abstinence (order counterbalanced). Following the imaging sessions, participants received brief smoking cessation counseling prior to a short-term (7-day) quit attempt. The primary smoking cessation outcome was biochemically confirmed 7-day relapse. The secondary smoking cessation outcome measure was total number of self-reported days of abstinence. During abstinence (vs satiety), smoking cue reactivity was significantly increased only in the anterior cingulate cortex (ACC); other regions showing a cue (vs neutral) response did not exhibit an abstinence effect in the stringent whole-brain analysis. Participants who showed greater smoking cue reactivity in the ACC during acute abstinence (compared with smoking satiety) were more likely to relapse (OR = 2.10 per standard deviation increase in percent signal change [abstinence minus smoking satiety], 95% CI: 1.05 to 4.20, P = 0.036). Greater abstinence-induced change in ACC activation also predicted fewer total days abstinent (β = -0.63, 95% CI = 0.43 to 0.66, P < 0.0001). This study provides the first evidence that changes in smoking cue reactivity in the ACC during acute abstinence predict smoking relapse, thereby improving our understanding of the neurobiology of smoking cessation.

Trial registration: ClinicalTrials.gov NCT02837510.

Keywords: BOLD fMRI; short-term relapse; smoking cue reactivity.

Figure 1

CONSORT participant flow diagram

Figure 2

Whole-brain analysis of CUE>neutral stimuli. Mean smoking cue reactivity (CUE>neutral) showing task active brain regions for all sessions (P ≤ 0.05, corrected)

Figure 3

Abstinence-induced change in neural cue reactivity predicts 7-day quit status. A, The whole-brain analysis of the abstinent>smoking satiety session revealed significant activation (red) in the anterior cingulate cortex (P ≤ 0.05, corrected). A mask (yellow) was generated using cluster correction procedures (Z ≥ 2.3, P ≤ 0.01) for percent signal change extraction. B, Participants who showed a greater increase in ACC percent signal change during abstinence (vs satiety) were more likely to relapse (OR = 2.10 per standard deviation increase in percent signal change, 95% CI: 1.05 to 4.20, P = 0.036)