Nicotine Withdrawal and Reward Processing: Connecting Neurobiology toReal-World Behavior

项目摘要/摘要 K23指导患者导向研究职业发展奖的目标是提供 候选人杰森·奥利弗博士，受过必要的培训，成为一名独立调查员 开展关于烟草使用和戒烟的翻译研究。目前对该问题的理解 驱动吸烟行为的机制是有限的，现有的戒烟治疗方法是 充其量也就是适度有效。拟议的培训和研究项目以一个新的框架为中心 理解吸烟行为，强调通过吸烟可获得的回报之间的不平衡 吸烟相对于其他不吸烟的环境奖励。这项研究将检验尼古丁的影响。 60名吸烟者对奖赏不平衡的戒断。创新战略将用于 系统地确定与个人相关的吸烟和替代奖励，以增强 这些奖励并增加了研究结果的潜力，为临床干预措施的发展提供了信息。一个 将使用翻译方法来评估实验室内的平行奖励反应以及 在实验室外使用移动技术进行实时监控。在第一个目标中，我们将检查尼古丁的影响 对与个人相关的吸烟和不吸烟奖赏图像的神经生物学反应的戒断 使用功能神经成像(FMRI)从吸烟者的自然环境中获取的刺激。在第二个目标中， 我们将研究戒断对他们从事这些行为的频率的影响，以及 奖励反应的大小。第三个目标将考察实验室和现实之间的关系- 世界的反应。研究结果将加深我们对奖赏失衡的神经机制的理解 这些机制在推动吸烟行为中所起的作用。作为更广泛的职业发展的一部分， 申请者，他将接受一个有经验的调查团队的培训，这些调查人员具有与 以上主题。亚当·莱文塔尔博士将提供有关替代奖励在吸烟中的作用的概念培训。 Scott Huettel博士将提供神经经济学的概念培训和功能的方法论培训 神经成像。让·贝克汉姆博士将提供评估现实世界吸烟的方法培训 行为。Robert Schnoll博士将提供吸烟临床试验设计和分析方面的培训 停止。约瑟夫·麦克勒农博士将全面指导专业人员，并为功能培训做出贡献 神经成像、戒烟临床试验和翻译研究计划的开发更多 大体上说。最终，该K23应用程序将为应聘者提供必要的培训和经验 担任独立研究科学家，从事有关吸烟的基础研究和应用研究 并在完成颁奖后成功竞争R01资金。

PROJECT SUMMARY/ABSTRACT The goal of this K23 Mentored Patient-Oriented Research Career Development Award is to provide the candidate, Dr. Jason Oliver, with the training necessary to establish a career as an independent investigator conducting translational research on tobacco use and smoking cessation. Current understanding of the mechanisms responsible for driving smoking behavior is limited and existing smoking cessation treatments are modestly effective at best. The proposed training and research project center on a novel framework for understanding smoking behavior emphasizing the imbalance between rewards attainable through cigarette smoking relative to other non-smoking environmental rewards. The study will examine the effects of nicotine withdrawal on reward imbalances among 60 cigarette smokers. An innovative strategy will be used to systematically identify personally-relevant smoking and alternative rewards in order to enhance the salience of the rewards and increase the potential for findings to inform the development of clinical interventions. A translational approach will be used to assess reward responses in parallel inside the laboratory as well as outside the lab in real-time using mobile technology. In the first aim, we will examine the effects of nicotine withdrawal on neurobiological responses to images of personally-relevant smoking and non-smoking reward stimuli taken from the smoker’s natural environment using functional neuroimaging (fMRI). In the second aim, we will examine the effects of withdrawal on the frequency with which they engage in these behaviors and the magnitude of the reward response. The third aim will examine the relationship between laboratory and real- world responses. Results will enhance our understanding of the neural mechanisms of reward imbalances and the role these mechanisms play in driving smoking behavior. As part of the broader career development of the applicant, he will receive training from a team of well-established investigators with expertise related to the above topics. Dr. Adam Leventhal will provide conceptual training in the role of alternative rewards in smoking. Dr. Scott Huettel will provide conceptual training in neuroeconomics and methodological training in functional neuroimaging. Dr. Jean Beckham will provide methodological training in the assessment of real-world smoking behavior. Dr. Robert Schnoll will provide training in the design and analysis of clinical trials for smoking cessation. Dr. Joseph McClernon will guide overall professional and contribute to training in functional neuroimaging, smoking cessation clinical trials and the development of a translational research program more broadly. Ultimately, this K23 application will provide the candidate with the training and experience necessary to function as an independent research scientist conducting both basic and applied research on smoking behavior and successfully compete for R01 funding upon completion of the award.