Nicotine Addiction and Reward Processing: An fMRI Investigation

描述(由申请者提供)：烟草使用是美国头号死因，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训练与成瘾中奖赏神经系统的研究相结合来满足这一使命。这项拟议的研究将检验吸烟者和不吸烟者在奖励预测任务上的总体差异，并评估冲动的调节影响。之前对吸烟者的神经成像研究发现，对尼古丁相关线索做出反应的奖赏神经系统存在差异。在自我报告和行为测量上，吸烟者也表现出比不吸烟者更高的冲动水平，而且冲动与对奖励的敏感性增强有关。然而，到目前为止，还没有研究检验吸烟者和不吸烟者之间奖赏神经系统的差异以及个人冲动的差异。奖赏神经系统包括从腹侧被盖区(VTA)到前额叶皮质(PFC)的多巴胺(DA)投射。这一建议假设，对奖励信号的过度敏感会导致尼古丁依赖参与者对奖励价值的高估，这种效应的强度将受到吸烟者冲动差异的调节。申请者将在轻度贫困的吸烟者和匹配的非吸烟者中使用奖励预测功能磁共振任务，其中第一个刺激呈现的预测准确率为75%，第二个刺激发出信号，预测奖励的发放或扣留。货币奖励和时间奖励都将给予。时间激励奖励将是时间积分，允许参与者提前离开实验(即，更早吸烟)。据预测，与非预测奖励相比，fMRI PFC激活最大，当预测奖励不提供时，激活最小，与低脉冲吸烟者和所有非吸烟者相比，这种影响在高冲动吸烟者中预计最为明显。此外，当给予时间激励时，上述PFC反应应该在吸烟者中放大。因此，应该在吸烟者中放大激活的强度，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的奖励系统如何做出不同的反应，这些结果可能被应用于设计有效的治疗方案，以解决吸烟者的个体差异。完成本提案的培训和研究部分将使申请者为从事神经成像和成瘾方面的翻译研究的独立调查员的职业生涯做好准备。

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.