Imaging temporal discounting in smokers and nonsmokers

描述（由申请人提供）：拟议研究的总体目的是确定与慢性药物滥用暴露相关的冲动决策的神经基质。这些信息对于理解习惯性药物使用的发展和停止具有潜在的重要意义。此外，它可能为动机系统和执行控制的神经认知机制的相互作用提供重要的见解，这是许多疾病的核心，如药物滥用，多动症和病理性赌博。在这个应用中，我们将使用时间贴现范式来评估冲动决策，在这个范式中，我们测量了对立即或很快获得的小奖励的偏好，以及对很久以后获得的大奖励的偏好。因此，本研究的具体目的是利用功能磁共振成像（fMRI）技术识别吸烟者和非吸烟者在时间折扣任务中的行为差异所对应的大脑激活模式的差异。该研究将使用事件相关设计来比较选择任务中的激活模式，该设计旨在将与时间折扣相关的处理与奖励维度（如大小和相对奖励即时性）的处理分开。我们假设，在时间折现过程中，当一种奖励选择立即可得而另一种奖励选择延迟可得时，吸烟者在腹侧纹状体（特别是伏隔核）、内侧OFC、内侧前额叶皮层、后扣带皮层的激活水平高于做出这些选择的非吸烟者（“区域”：McClure et al., 2004; 2007）。相比之下，不吸烟者在腹外侧和背外侧前额叶皮层、右侧OFC和后顶叶皮层（“区域”）的激活水平比吸烟者高。在时间折扣中，当两种奖励选择都被延迟时，我们预测非吸烟者在该区域也会表现出比吸烟者更高的激活水平。PI已经参与了一项受资助的研究，研究将时间折扣和吸烟联系起来的行为机制。这项拟议中的研究将使她能够迈出第一步，利用功能磁共振成像技术探索神经区域和这些区域之间的相互关系。潜在的健康影响：这项研究将确定当个体评估不同奖励大小和延迟时间的替代方案的主观价值时所涉及的大脑区域。它还将确定当个体表达对不同选择的偏好时所涉及的区域，以及吸烟者和非吸烟者在这些偏好背后的激活模式上的任何差异。了解哪些结构参与了这种决策以及它们之间的联系，可能会为那些由于长期吸毒、事故或中风而表现出冲动决策的人提供个性化的治疗目标。

DESCRIPTION (provided by applicant): The overall aim of the proposed research is to identify the neural substrates of impulsive decision making associated with chronic exposure to drugs of abuse. Such information is potentially important for understanding the development and cessation of habitual drug use. Furthermore, it may provide important insights into the interaction of motivational systems and neurocognitive mechanisms of executive control, which are central to a number of disorders such as drug abuse, ADHD and pathological gambling. In this application, impulsive decision making will be assessed using a temporal discounting paradigm in which we measure preference for small rewards available either immediately or soon versus larger rewards available much later. Accordingly, the specific aim of the research proposed here is to identify differences in brain activation patterns in smokers and nonsmokers corresponding to the behavioral differences on a temporal discounting task using functional magnetic resonance imaging (fMRI) techniques. The study will use an event-related design to compare activation patterns during choice tasks designed to separate processing associate with temporal discounting from processing of reward dimensions like size and relative reward immediacy. We hypothesize that, during temporal discounting, when one reward alternative is available immediately and the other delayed, smokers will exhibit higher levels of activation in ventral striatum (esp. nucleus accumbens), medial OFC, medial prefrontal cortex, posterior cingulate cortex than nonsmokers making these choices (" areas": McClure et al., 2004; 2007). In contrast, nonsmokers will exhibit higher levels of activation in ventrolateral and dorsolateral prefrontal cortex, right lateral OFC and posterior parietal cortex (" areas") than smokers. During temporal discounting when both reward alternatives are delayed, we predict that nonsmokers will also exhibit higher levels of activation in the areas compared to smokers. The PI is already engaged in funded research examining the behavioral mechanisms linking temporal discounting and cigarette smoking. The proposed research would permit her to take the first step towards exploring the neural regions and inter-relationships between these regions using fMRI techniques. Potential health impact: This research will identify areas of the brain that are involved when individuals evaluate the subjective value of alternatives differing in their reward size and the delay until their availability. It will also identify areas that are involved when individuals express a preference between the alternatives, and any differences between smokers and nonsmokers in activation patterns underlying these preferences. Understanding which structures are involved in such decision making and their connectivity, may suggest individualized treatment targets for people exhibiting impulsive decision-making due to chronic drug use, accident or stroke.