Caudate reactivity to smoking cues is associated with increased responding to monetary reward in nicotine-dependent individuals

Abstract

Quitting smoking is challenging in part because environmental smoking cues can trigger the desire to smoke. Neurobiological responses to smoking cues are often observed in reward-related brain regions such as the caudate and nucleus accumbens (NAc). While reward plays a well-established role in the formation of cue reactivity, whether general reward responsiveness contributes to individual differences in cue-reactivity among chronic smokers is unclear; establishing such link could provide insight into the mechanisms maintaining cue reactivity. The current study explored this relationship by assessing smoking cue reactivity during functional magnetic imaging followed by an out-of-scanner probabilistic reward task (PRT) in 24 nicotine-dependent smokers (14 women). In addition, owing to sex differences in cue reactivity and reward function, this same relationship was examined as a function of sex. Following recent smoking, greater reward responsiveness on the PRT was associated with enhanced left caudate reactivity to smoking cues. No relationship was found in any other striatal subregion. The positive relationship between reward responsiveness and caudate smoking cue reactivity was significant only in male smokers, fitting with the idea that males and females respond to the reinforcing elements of smoking cues differently. These findings are clinically relevant as they show that, following recent smoking, nicotine-dependent individuals who are more cue reactive are also more likely to be responsive to non-drug rewards, which may be useful for making individualized treatment decisions that involve behavioral reward contingencies.

Keywords: Addiction; Caudate; Cue-Reactivity; Nicotine; Nucleus accumbens; Reward responsivity; Sex differences; Smoking.

Figure 1.. Multivariate regression results for striatal ROIs and response bias for overall sample.

A, B. Plots of left and right caudate beta weights from smoking > neutral contrast from cue reactivity paradigm against change in response bias in probabilistic reward task. ΔRB significantly predicted the left caudate in a positive direction. ΔRB approached significance for the right caudate. C, D. Plots of left and right NAc beta weights from smoking > neutral contrast from cue reactivity paradigm against change in response bias in probabilistic reward task. ΔRB did not significantly predict left or right NAc.

Figure 2.. Multivariate regression results for striatal ROIs and response bias based on Sex.

Plots of smoking > neutral beta weights extracted from fMRI cue reactivity paradigm for left and right caudate for male and female subsamples. For male participants, ΔRB showed a significant association with left caudate smoking > neutral cue activation and approached significance for right caudate cue activation.