Nicotine Addiction and Reward Processing: An fMRI Investigation

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DESCRIPTION (provided by applicant): Tobacco use is the number one cause of death in the US and a major mission of NIDA involves advancing research and training examining the neural bases of addiction. The current proposal meets this mission by combining training in nicotine addiction with research on the neural systems of reward in addiction. The proposed research will examine general differences between smokers and nonsmokers on a reward prediction task and evaluate the modulating influence of impulsivity. Previous neuroimaging studies in smokers have found differences in the neural systems of reward in response to nicotine-related cues. Cigarette smokers also show higher levels of impulsivity compared to non-smokers on self-report and behavioral measures, and impulsivity has been associated with enhanced sensitivity to reward. However, no studies to date have examined differences in the neural systems of reward and individual differences in impulsivity among cigarette smokers and nonsmokers. The neural systems of reward involve dopaminerigic (DA) projections from the ventral tegmental area (VTA) to regions of the prefrontal cortex (PFC). This proposal hypothesizes that hypersensitivity to reward signals leads to overestimation of reward values among nicotine dependent participants, and that the strength of this effect will be modulated by differences in impulsivity among smokers. The applicant will use a reward prediction fMRI task, in mildly deprived smokers and matched nonsmokers, in which the first stimulus presented predicts with 75% accuracy the delivery or withholding of a reward, signaled by a second stimulus. Both monetary and time incentive rewards will be given. The time incentive reward will be time credits allowing participants to leave the experiment early (i.e., smoke sooner). It is predicted that fMRI PFC activations will be largest to nonpredicted rewards and smallest when predicted rewards are not delivered, and this effect is expected to be most pronounced among high impulsive smokers compared to low impulsive smokers and all non-smokers. Moreover, when time incentives are given, the above mentioned PFC responses should be amplified among smokers. Thus, the strength of activations should be amplified among smokers and will be modulated by both levels of impulsivity and the nature of the incentive. By gaining a better understanding of the how reward systems respond differentially in the nicotine dependent and impulsive brain, these results may be applied to designing effective treatment programs that address individual differences among smokers. Completion of both the training and research components of this proposal will prepare the applicant for a career as an independent investigator carrying out translational research in neuroimaging and addiction.