Neural substrates of smoking and reward cue reactivity in smokers: a meta-analysis of fMRI studies

Smoking is partly attributed to alterations of reward processing. However, findings on the neurobiological mechanisms that underlie smoking-related and smoking-unrelated reward processing in smokers have been inconsistent. Neuroimaging experiments that used functional magnetic resonance imaging (fMRI) and reported brain responses to smoking-related cues and nonsmoking reward-related cues in smokers and healthy controls as coordinates in a standard anatomic reference space were identified by searching the PubMed, Embase, and Web of Science databases up to December 2018. Three meta-analyses were performed using random-effect nonparametric statistics with Seed-based d Mapping software, with brain activity contrast from individual studies as the input. The striatum showed higher activation in response to smoking-related cues compared with neutral cues in 816 smokers from 28 studies and lower activation in response to nonsmoking reward-related cues in 275 smokers compared with 271 healthy control individuals from 13 studies. The relative reactivity of the putamen to smoking-related cues increased in 108 smokers compared with 107 healthy controls from seven studies. Meta-regression showed that smokers with a greater severity of nicotine dependence exhibited less engagement of the striatum in response to both smoking-related cues and nonsmoking reward-related cues. The present results reveal the disruption of reward system function in smokers and provide new insights into diverging theories of addiction. With the escalation of nicotine dependence, nicotine appears to exert dynamic effects on reward processing, based on incentive sensitization theory and reward deficiency syndrome theory.