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

Xiao Lin,Le Shi,Lin Lu,Daniel R Weinberger,Jiahui Deng,Peng Li,Jie Shi,Jiajia Liu,Suhua Chang,Ping Wu,Jianyu Que,Qiandong Wang,Hui Li,Yanping Bao

doi:10.1038/s41398-020-0775-0

Abstract

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.

Highlights

Cigarette smoking is a chronic relapsing disorder and one of the leading causes of preventable disease and death
Activation of the striatum and anterior cingulate gyrus increased in response to smoking-related cues vs. neutral cues in smokers
The meta-regression analysis showed that sensitivity of the reward system was disrupted as the severity of nicotine dependence increased, with lower activation of the striatum in response to smoking-related cues and nonsmoking reward-related cues in smokers with higher FTND scores

Summary

Introduction

Cigarette smoking is a chronic relapsing disorder and one of the leading causes of preventable disease and death. Yearly smoking-related deaths are expected to rise to 8 million by 20302. Most smokers report a desire to quit, the majority of attempts fail within 10 days[3]. Numerous studies reported that craving that is induced by smoking-related cues is responsible for the failure to quit and high rates of relapse[4,5]. One core characteristic of addiction is the disruption of reward processing[6], which influences decision-making and leads to smoking behavior[7,8]. The relationship between alterations of reward processing and nicotine dependence has been well demonstrated, but no consensus has been reached on

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Conclusion