title: Nicotine Withdrawal Induces Neural Deficits in Reward Processing.
abstract: BACKGROUND
  Nicotine withdrawal reduces neurobiological responses to nonsmoking rewards. Insight into these reward deficits could inform the development of targeted interventions. This study examined the effect of withdrawal on neural and behavioral responses during a reward prediction task.
  
  
  METHODS
  Smokers (N = 48) attended two laboratory sessions following overnight abstinence. Withdrawal was manipulated by having participants smoke three regular nicotine (0.6 mg yield; satiation) or very low nicotine (0.05 mg yield; withdrawal) cigarettes. Electrophysiological recordings of neural activity were obtained while participants completed a reward prediction task that involved viewing four combinations of predictive and reward-determining stimuli: (1) Unexpected Reward; (2) Predicted Reward; (3) Predicted Punishment; (4) Unexpected Punishment. The task evokes a medial frontal negativity that mimics the phasic pattern of dopaminergic firing in ventral tegmental regions associated with reward prediction errors.
  
  
  RESULTS
  Nicotine withdrawal decreased the amplitude of the medial frontal negativity equally across all trial types (p < .001). Exploratory analyses indicated withdrawal increased time to initiate the next trial following unexpected punishment trials (p < .001) and response time on reward trials during withdrawal was positively related to nicotine dependence (p < .001).
  
  
  CONCLUSIONS
  Nicotine withdrawal had equivocal impact across trial types, suggesting reward processing deficits are unlikely to stem from changes in phasic dopaminergic activity during prediction errors. Effects on tonic activity may be more pronounced. Pharmacological interventions directly targeting the dopamine system and behavioral interventions designed to increase reward motivation and responsiveness (eg, behavioral activation) may aid in mitigating withdrawal symptoms and potentially improving smoking cessation outcomes.
  
  
  CONCLUSIONS
  Findings from this study indicate nicotine withdrawal impacts reward processing signals that are observable in smokers' neural activity. This may play a role in the subjective aversive experience of nicotine withdrawal and potentially contribute to smoking relapse. Interventions that address abnormal responding to both pleasant and unpleasant stimuli may be particularly effective for alleviating nicotine withdrawal.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Oliver
authors.affiliation: Department of Health Outcomes and Behavior, Moffitt Cancer Center, Tampa, FL.|Department of Psychology, University of South Florida, Tampa, FL.
authors.forename: David E
authors.initials: DE
authors.lastname: Evans
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC.
authors.forename: Merideth A
authors.initials: MA
authors.lastname: Addicott
authors.affiliation: Department of Psychology, University of South Florida, Tampa, FL.
authors.forename: Geoffrey F
authors.initials: GF
authors.lastname: Potts
authors.affiliation: Department of Health Outcomes and Behavior, Moffitt Cancer Center, Tampa, FL.|Department of Psychology, University of South Florida, Tampa, FL.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Brandon
authors.affiliation: Department of Health Outcomes and Behavior, Moffitt Cancer Center, Tampa, FL.|Department of Psychology, University of South Florida, Tampa, FL.
authors.forename: David J
authors.initials: DJ
authors.lastname: Drobes
mesh_terms: D000328:Adult; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D004569:Electroencephalography; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009538:Nicotine / Q000494:pharmacology*; D012201:Reward; D016540:Smoking Cessation; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*; D014029:Tobacco Use Disorder / Q000503:physiopathology*; D055815:Young Adult
chemical_list: D009538:Nicotine