Evidence for a hijacked brain reward system but no desensitized threat system in quitting-motivated smokers: An fMRI study.

BACKGROUND AND AIMS Several aspects of how quitting-motivated tobacco use disorder (TUD) subjects and never-smokers differ in terms of reward and threat processing remain unresolved. We aimed to examine aberrant reward and threat processes in TUD and the association with smoking characteristics. DESIGN A between- and within-subjects functional magnetic resonance imaging (fMRI) experiment with a 2 (groups) × 4 (stimulus type) factorial design. The experimental paradigm had four conditions: pictures of (1) cigarettes served as drug-related-positive cues, (2) food as alternative reward cues, (3) long-term consequences of smoking as drug-related-negative cues and (4) neutral pictures as control. SETTING/PARTICIPANTS Adult participants (n = 38 TUD subjects and n = 42 never-smokers) were recruited in Berlin, Germany. MEASUREMENTS As contrasts of primary interest, the interactions of group × stimulus-type were assessed. Significance threshold correction for multiple testing was carried out with the family-wise error method. Correlation analyses were used to test the association with smoking characteristics. FINDINGS The 2 × 2 interaction of smoking status and stimulus type revealed activations in the brain reward system to drug-related-positive cues in TUD subjects (between-subjects effect: P-values ≤ 0.036). As a response to drug-related-negative cues, TUD subjects showed no reduced activation of the aversive brain network. Within the TUD group, a significant negative association was found between response of the aversive brain system to drug-related-negative cues (within-subjects effect: P-values ≤ 0.021) and the number of cigarettes smoked per day (right insula r = -0.386, P = 0.024; left insula r = -0.351, P = 0.042; right ACC r = -0.359, P = 0.037). CONCLUSIONS Moderate smokers with tobacco use disorder appear to have altered brain reward processing of drug-related-positive (but not negative) cues compared with never smokers.