Nicotine Addiction and Reward Processing: An fMRI Investigation

尼古丁成瘾和奖励处理：功能磁共振成像研究

• 批准号: 7275040
• 负责人: Laura E Martin
• 金额: $ 4.7万
• 依托单位: UNIVERSITY OF KANSAS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-06-17 至 2009-06-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7275040
• 关键词: Address; Alcohol or Other Drugs use; Alcohols; Area; Brain; Cause of Death; Characteristics; Cigarette; Cigarette Smoker; Cognitive; Cues; Decision Making; Dependence; Event-Related Potentials; Functional Magnetic Resonance Imaging; Health; Hypersensitivity; Impulse Control Disorders; Impulsivity; Incentives; Individual Differences; Investigation; Knowledge; Lead; Left; Methods; Mission; National Institute of Drug Abuse; National Research Service Awards; Nature; Nicotine; Nicotine Dependence; Numbers; Participant; Patient Self-Report; Personality; Prefrontal Cortex; Process; Punishment; Purpose; Questionnaires; Research; Research Personnel; Research Training; Rewards; Role; Signal Transduction; Smoke; Smoker; Smoking; Stimulus; System; Time; Tobacco; Tobacco use; Training; Translational Research; United States; Ventral Tegmental Area; Work; addiction; base; behavior measurement; career; cigarette smoking; design; experience; neuroimaging; non-smoker; pre-doctoral; relating to nervous system; research study; response; reward processing; treatment program; university student

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.

描述（由申请人提供）：烟草使用是美国第一大死因，NIDA 的一项主要使命是推进研究和培训成瘾的神经基础。目前的提案通过将尼古丁成瘾训练与成瘾奖赏神经系统研究相结合来实现这一使命。拟议的研究将检查吸烟者和非吸烟者在奖励预测任务上的一般差异，并评估冲动的调节影响。之前对吸烟者的神经影像学研究发现，奖励神经系统对尼古丁相关线索的反应存在差异。在自我报告和行为测量中，与不吸烟者相比，吸烟者也表现出更高水平的冲动，而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奖励神经系统的差异以及冲动的个体差异。奖赏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。该提议假设，对奖励信号的过敏会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通过吸烟者之间冲动性的差异来调节。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功能磁共振成像任务，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提供或扣留。将给予金钱和时间奖励。时间激励奖励将是时间积分，允许参与者提前离开实验（即更快地吸烟）。据预测，fMRI PFC 激活对于非预测奖励而言最大，而当未提供预测奖励时则最小，并且与低冲动吸烟者和所有非吸烟者相比，这种效应预计在高冲动吸烟者中最为明显。此外，当给予时间奖励时，上述 PFC 反应应在吸烟者中放大。因此，吸烟者的激活强度应该被放大，并受到冲动水平和激励性质的调节。通过更好地了解奖励系统在尼古丁依赖和冲动大脑中如何做出不同的反应，这些结果可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作为一名独立调查员在神经影像和成瘾领域开展转化研究做好准备。