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因，NIDA的主要使命包括推进研究和培训，检查成瘾的神经基础。目前的建议满足这一使命结合尼古丁成瘾的培训与成瘾的神经系统奖励的研究。这项研究将检查吸烟者和不吸烟者在奖励预测任务中的一般差异，并评估冲动性的调节影响。以前对吸烟者的神经影像学研究发现，尼古丁相关线索引起的奖赏神经系统存在差异。吸烟者在自我报告和行为测量方面也表现出比不吸烟者更高的冲动水平，冲动与对奖励的敏感性增强有关。然而，迄今为止，还没有研究检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。奖赏的神经系统涉及从腹侧被盖区（VTA）到前额叶皮层（PFC）区域的多巴胺（DA）投射。该提案假设对奖励信号的超敏反应导致尼古丁依赖参与者对奖励值的高估，并且这种效应的强度将受到吸烟者冲动性差异的调节。申请人将使用奖励预测功能磁共振成像任务，在轻度剥夺吸烟者和匹配的非吸烟者中，其中第一个刺激以75%的准确度预测第二个刺激发出的奖励的交付或扣留。将给予金钱和时间激励奖励。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，吸烟更快）。据预测，fMRI PFC激活将是最大的非预测奖励和最小的预测奖励时，没有交付，这种效果预计将是最明显的高冲动吸烟者相比，低冲动吸烟者和所有非吸烟者。此外，当给予时间激励时，上述PFC反应在吸烟者中应被放大。因此，激活的强度应该在吸烟者中被放大，并将受到冲动程度和激励性质的调节。通过更好地了解尼古丁依赖性和冲动性大脑中奖励系统的反应差异，这些结果可能适用于设计有效的治疗方案，以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的职业生涯做好准备，作为一名独立的研究人员在神经影像学和成瘾方面进行转化研究。

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.