Smokers and ex‐smokers have shared differences in the neural substrates for potential monetary gains and losses

Abstract

Abstract:Despite an increased understanding of nicotine addiction, there is a scarcity of research comparing the neural correlates of non-drug reward between smokers and ex-smokers. Long-term changes in reward-related brain functioning for non-drug incentives may elucidate patterns of functioning that potentially contribute to ongoing smoking behaviour in current smokers. Similarly, examining the effects of previous chronic nicotine exposure during a period of extended abstinence may reveal whether there are neural correlates responsible for non-drug reward processing that are different from current smokers. The current study, therefore, set out to examine the neural correlates of reward and loss anticipation, and their respective outcomes, in smokers, ex-smokers and matched controls using a monetary incentive delay task during functional MRI. Here we report that in the absence of any significant behavioural group differences, both smokers and ex-smokers showed a significantly greater activation change in the lateral orbitofrontal/anterior insular cortex compared to smokers when anticipating both potential monetary gains and losses. We further report that ex-smokers showed a significantly greater activation change in the ventral putamen compared to both controls and smokers, and in the caudate compared to controls during the anticipation of potential monetary losses only. The results suggest that smoking may sensitize striato-orbitofrontal circuitry subserving motivational processes for loss avoidance and reward gain in nicotine addiction. Comments to the Author This is a revision of an article detailing brain response differences between smokers, ex-smokers and non-smokers using the monetary incentive delay task. The authors did a great job addressing previous concerns and clarifying the analysis methods.A major limitation of the study is the sample size which could only be addressed by recruiting more subjects, despite this limitation the study is the first step towards dissociating theoretical models of reward processing in smokers.The inclusion of the mask in the supplemental materials is helpful, however, the inclusion of the whole-brain analysis in the supplemental materials would be helpful (although not necessary). The exploratory whole brain analysis demonstrates that the ROI approach did not miss any key reward processing regions. New Author Response: We have now included the ROI mask as a supplementary figure.Reviewer: 1 Comments to the Author SummaryThis report titled 'Smokers and ex-smokers have shared differences in the neural substrates for potential monetary gains and losses' tests the neural correlates of reward and loss anticipation and outcomes via the Monetary Incentive Delay task during fMRI in current cigarette smokers, exsmokers, and non-smoking young adults. This reviewer continues to have no major concerns, but there were some responses that may require further thought and elaboration (outlined below) before this paper is accepted for publication. Materials and MethodsfMRI Data Analysis ...

Dopamine Transporter Gene Methylation is Associated with Nucleus Accumbens Activation During Reward Processing in Healthy but not Alcohol‐Dependent Individuals

“…Nevertheless, the group differences in smoking may have influenced our results. That is, similarly to alcohol, smoking a cigarette increases dopamine release in the midbrain (Brody et al, 2004), and chronic smoking leads to disruptions in the dopaminergic system including lower striatal dopamine D2 receptor availability (e.g., Albrecht et al, 2013; Wiers et al, 2017) and neural responses to the MID task (e.g., Fedota et al, 2015; Nestor et al, 2016). Whether smoking also influences SLC6A3 methylation, however, remains unknown.…”

The Effects of Nicotine and Tobacco Use on Brain Reward Function: Interaction With Nicotine Dependence Severity

“…Smokers showed more cue-related VMPFC activation during the satiated condition than nonsmokers during the placebo condition, although the hypothesized differences in striatal activation were not found. Previous studies that compared MID rewardrelated activation between smokers and nonsmokers have shown that smokers have less activation in the frontal cortex, 14,15 NAcc, 14,15 and caudate, 15 or more activation in the frontal cortex 16 and caudate. 14 Greater activation has been interpreted to represent stronger reward-related motivation or salience for nondrug rewards, which may be diminished in smokers, 14 or enhanced by nicotine exposure.…”

“…The MID has been used to investigate the influence of addictive drugs on the neural response to the anticipation and receipt of nondrug rewards. 13 In particular, previous research has shown differences between smokers and nonsmokers, [14][15][16] as well as effects of nicotine and withdrawal 14,15 in reward-related brain activation. While this research demonstrates the sensitivity of the MID to nicotine manipulations, results have been inconsistent.…”

Functional Neurocircuits and Neuroimaging Biomarkers of Tobacco Use Disorder

“…Placing these observations in the larger context of TUD, accumulating evidence links an extended smoking history with striatal hypoactivity during monetary-reward processing tasks [25, 55, 57–61], albeit, not consistently [62, 63]. More severe striatal hypoactivity to aspects of monetary reward has been associated with poorer outcomes among smokers when considering the number of cigarettes smoked per day [64], craving severity [56], their ability to briefly refrain from smoking [59], and, ultimately, relapse rates [58].…”