Dopamine Influences on Self-Regulation and Impulsivity

项目摘要 我们最近报道，中脑多巴胺（DA）自身受体水平与自我报告的 冲动这一发现表明，DA释放自动调节控制降低的个体， 易受冲动影响，因为控制与接近相关的动机驱动的能力降低 由DA神经传递提供。然而，自我报告措施不允许直接审查 被认为在冲动中被削弱的行为控制的核心过程。目前，关系 DA自身感受器和冲动性背后的特定过程之间的联系尚不清楚，因为冲动性是一种多功能的 冲动的分面结构和行为测量与自我报告量表仅适度相关。 为了阐明DA功能和冲动性之间的联系，我们建议测量中脑DA自身受体， 28名健康成年人的冲动性的可用性和行为和功能磁共振成像指数。中脑 纹状体和皮质中的自身受体可用性以及D2样受体可用性将用 高亲和力PET D2/D3配体[18F]fallypride。所有参与者将完成一个奖励停止信号任务 (SST)和时间（延迟）贴现（TD）范式，以提供行为的客观措施， 控制SST和TD范式捕捉了冲动性的两个不同方面（停止和奖励决策）， 制造），其涉及不同的，尽管重叠的神经网络。通过在fMRI中完成这些任务，我们 将能够测试中脑DA自身受体水平的个体差异是否会影响反应性 参与自我调节的大脑区域（例如，前扣带回、腹侧纹状体、右额下回）。 我们还将测试目标行为控制区域中的D2受体可用性是否可预测 在任务执行过程中BOLD激活的程度，从而提供了检查机械模型的能力 DA功能的个体差异与行为相关区域的参与之间的联系 控制在TD的情况下，我们将评估降低的自身受体控制导致更大的 神经核对即时奖励的大胆反应，导致更冲动的选择。为了 为了弥合当前DA功能理论和停止的认知科学，我们开发了一种新的， SST的奖励版本，用于评估奖励改变的走和停反应时间的程度 上下文这可能被证明是至关重要的定义DA的行为控制的影响的具体性质。等 在SST范式中，奖励操纵还没有得到广泛的研究，尽管大多数现实生活中 冲动控制问题出现在高动机的背景下。100名参与者（以及 28名被扫描的参与者）将完成奖励的SST以及一系列自我报告和行为测量 来进一步描述这种新的模式。总的来说，这个项目的桥梁认知和情感 科学和神经科学、行为经济学、神经药理学和人格研究提供了一个 理解奖励对行为控制和自我调节的影响的框架。

Project Summary We recently reported that levels of midbrain dopamine (DA) autoreceptors are inversely related to self-reported impulsivity. This finding suggests that individuals with reduced autoregulatory control of DA release are susceptible to impulsivity because of a reduced ability to control the approach-related motivational drive provided by DA neurotransmission. However, self-report measures do not allow for a direct examination of the core processes of behavioral control that are thought to be weakened in impulsivity. At present, the relation between DA autoreceptors and specific processes underlying impulsivity is unknown, as impulsivity is a multi- faceted construct and behavioral measures of impulsivity are only modestly associated with self-report scales. To clarify the link between DA functioning and impulsivity, we propose to measure midbrain DA autoreceptor availability and behavioral and fMRI indices of impulsivity in a group of 28 healthy adults. Midbrain autoreceptor availability, as well as D2-like receptor availability in the striatum and cortex will be assessed with the high affinity PET D2/D3 ligand [18F]fallypride. All participants will complete a rewarded stop signal task (SST) and a temporal (delay) discounting (TD) paradigm in order to provide objective measures of behavioral control. The SST and TD paradigms capture two distinct aspects of impulsivity (stopping and reward decision- making), which engage distinct, albeit overlapping neural networks. By completing these tasks during fMRI, we will be able to test whether individual differences in midbrain DA autoreceptor levels influence the responsivity of brain areas involved in self-regulation (e.g., anterior cingulate, ventral striatum, right inferior frontal gyrus). We will also test whether D2-receptor availability in the target behavioral control regions is predictive of the degree of BOLD activation during task performance, thus providing an ability to examine mechanistic models of the link between individual differences in DA functioning and the engagement of areas involved in behavioral control. In the case of TD, we will assess the hypothesis that lowered autoreceptor control leads to greater BOLD responses in the nucleus accumbens for immediate rewards, leading to more impulsive choice. In order to bridge current theories of DA functioning and the cognitive science of stopping, we have developed a novel, reward version of the SST that assesses the extent to which go and stop reaction times are altered by reward context. This may prove critical for defining the specific nature of DA's impact on behavioral control. Such reward manipulations have not been widely examined in the SST paradigm, despite the fact that most real-life impulse control problems arise in the context of high motivation. One hundred additional participants (and the 28 scanned participants) will complete the rewarded SST and a battery of self-report and behavioral measures of impulsivity to further characterize this new paradigm. Overall, this project bridges cognitive and affective science and neuroscience, behavioral economics, neuropharmacology and personality research to provide a framework for understanding reward influences on behavioral control and self-regulation.