Acute and Chronic Nicotine Modulation of Reinforcement Learning

描述(申请人提供)：这项研究的目的是调查急性和慢性尼古丁暴露对强化学习的调节作用，以换取金钱奖励。尼古丁是烟草中的主要成瘾成分，是一种弱增强剂，不会像其他滥用药物(如可卡因、酒精)那样产生强烈的愉悦效果，但烟草使用者的依赖率高于其他成瘾药物使用者。对这一悖论的一个潜在解释是，尼古丁放大了 其他具有一定激励价值和长时间暴露的刺激可能会导致奖励过程的失调。强化学习是学习采取什么行动以最大化奖励的过程，也可能是尼古丁放大其他刺激的激励价值的机制。强化学习的一个关键组成部分是预测误差，即实际奖励结果与预期奖励结果之间的差异。神经成像研究表明，中皮质边缘通路的BOLD激活与强化学习范例中的预测错误相关。这项建议的主要目的是使用强化学习的神经经济学模型来研究尼古丁对动机行为的急性和慢性影响，并使用具有概率结果和功能磁共振的任务来预测错误相关的神经激活。非吸烟者将在急性尼古丁和安慰剂注射后接受扫描，吸烟者将在正常吸烟行为和24小时戒烟后接受扫描。这一建议将弥合神经经济学和成瘾研究之间的文献差距，这些结果将揭示尼古丁对强化学习的影响是否可以促进吸烟行为的启动和维持。首席调查员(PI)将由具有尼古丁精神药理学、功能磁共振成像和神经经济学专业知识的教职员工团队指导和建议。该机构提供专门从事这三个领域研究的特殊设施和部门。除了学习如何设计和进行临床尼古丁研究外，这项培训计划还为私人投资公司提供了整合几个不同但重叠的研究领域的机会，以探索了解尼古丁成瘾病因的新方法。这项建议建立在PI之前的药物-核磁共振经验的基础上，并将使她能够发展新的技能，同时为研究尼古丁对人类决策行为的影响做出贡献。本提案中描述的教育、培训和研究目标将为申请者提供成为一名成功的独立调查员所必需的研究经验。

DESCRIPTION (provided by applicant): The purpose of this study is to investigate the modulatory effects of acute and chronic nicotine exposure on reinforcement learning for monetary rewards. Nicotine, the primary addictive component in tobacco, is a weak reinforcer that does not induce robust euphoric effects like other drugs of abuse (e.g., cocaine, alcohol), yet produces a higher rate of dependence among tobacco users than among users of other addictive drugs. A potential explanation of this paradox is that nicotine amplifies the salience of other stimuli that have some incentive value and prolonged exposure could result in dysregulated reward processing. Reinforcement learning is the process of learning what actions to take to maximize reward, and may be the mechanism by which nicotine amplifies the incentive value of other stimuli. A key component of reinforcement learning is the prediction error, which is the difference between the actual and the expected reward outcome. Neuroimaging studies have shown that BOLD activation in the mesocorticolimbic pathway correlates with prediction errors during reinforcement learning paradigms. The overarching aim of this proposal is to use neuroeconomic models of reinforcement learning to study the acute and chronic effects of nicotine on motivational behavior and prediction error-related neural activation using a task with probabilistic outcomes and fMRI. Nonsmokers will be scanned following acute nicotine and placebo administration, and smokers will be scanned following normal smoking behavior and 24-hours of smoking abstinence. This proposal will bridge the gap in the literature between neuroeconomic and addiction research and these results will inform whether the initiation and maintenance of smoking behavior could be facilitated by the effects of nicotine on reinforcement learning. The Principal Investigator (PI) will be mentored and advised by a team of faculty with expertise in nicotine psychopharmacology, fMRI, and neuroeconomics. The institution provides exceptional facilities and departments dedicated to these three fields of research. In addition to learning how to design and conduct clinical nicotine research, this training plan with provide the PI with the opportunity to integrate several distinct, yet overlapping, fields of research in order to explore new approaches to understanding the etiology of nicotine addiction. This proposal builds upon the PI's previous pharmaco-MRI experience, and will allow her to develop new skills while contributing to research on the effects of nicotine on decision-making behavior in humans. The education, training, and research goals described in this proposal will provide the applicant with the research experience necessary to become a successful independent investigator.