Nicotine Addiction and Reward Processing: An fMRI Investigation

描述（由申请人提供）：烟草使用是美国的头号死亡原因，NIDA的一项主要任务是推进研究和培训，检查成瘾的神经基础。目前的建议通过将尼古丁成瘾的训练与成瘾中的奖励神经系统的研究相结合来实现这一使命。这项拟议的研究将检验吸烟者和非吸烟者在奖励预测任务上的一般差异，并评估冲动的调节作用。先前对吸烟者进行的神经成像研究发现，在对尼古丁相关线索作出反应时，神经系统的奖励机制存在差异。与不吸烟者相比，吸烟者在自我报告和行为测量中也表现出更高的冲动水平，而冲动与对奖励的敏感度增强有关。然而，到目前为止，还没有研究调查吸烟者和不吸烟者之间奖励神经系统的差异和冲动的个体差异。奖励神经系统涉及从腹侧被盖区（VTA）到前额皮质（PFC）区域的多巴胺能（DA）投射。该研究假设，对奖励信号的过度敏感导致尼古丁依赖参与者对奖励值的高估，而这种影响的强度将受到吸烟者冲动程度的差异的调节。申请人将在轻度剥夺吸烟者和匹配的非吸烟者中使用奖励预测fMRI任务，其中第一个刺激以75%的准确率预测由第二个刺激发出的奖励的传递或保留。将给予金钱和时间奖励。时间激励奖励将是允许参与者提前离开实验的时间积分（即更早吸烟）。据预测，fMRI PFC的激活对于非预测的奖励是最大的，而当预测的奖励没有传递时是最小的，与低冲动性吸烟者和所有不吸烟者相比，这种影响在高冲动性吸烟者中最为明显。此外，当给予时间激励时，上述PFC反应应在吸烟者中被放大。因此，在吸烟者中，激活的强度应该被放大，并将受到冲动水平和激励性质的调节。通过更好地了解尼古丁依赖和冲动大脑中奖励系统的不同反应，这些结果可以应用于设计有效的治疗方案，解决吸烟者之间的个体差异。完成本提案的培训和研究部分将为申请人作为一名独立研究者在神经成像和成瘾方面进行转化研究做好准备。

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.