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水平呈负相关 冲动。这一发现表明，对DA释放的自我调节控制减弱的个体 容易冲动，因为控制与接近相关的动机动力的能力降低 由DA神经传递提供。然而，自我报告措施不允许直接检查 被认为在冲动中被削弱的行为控制的核心过程。目前，两国关系 DA自身受体和冲动的具体过程之间的关系尚不清楚，因为冲动是一种多方面的 冲动性的刻面结构和行为测量只与自我报告量表有适度的联系。 为了阐明DA功能和冲动之间的联系，我们建议测量中脑DA自身受体 一组28名健康成年人的可获得性以及冲动的行为和功能磁共振指数。中脑 纹状体和皮质中自身受体的可用性以及D2样受体的可用性将通过 高亲和力的PET D2/D3配体[18F]自豪感。所有参与者将完成一项有奖励的停车信号任务 (SST)和时间(延迟)贴现(TD)范例，以便提供行为的客观测量 控制力。SST和TD范例捕捉到冲动的两个不同方面(停止和奖励决策-- 制造)，这与截然不同但重叠的神经网络相结合。通过在功能磁共振期间完成这些任务，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响应性 参与自我调节的脑区(如前扣带回、腹侧纹状体、右下额下回)。 我们还将测试目标行为控制区中D2受体的可用性是否可以预测 在任务执行期间大胆激活的程度，从而提供了检查机械模型的能力 DA功能的个体差异与参与行为活动的区域之间的联系 控制力。在TD的情况下，我们将评估以下假设：降低自身受体控制会导致更大的 伏隔核中的大胆反应是为了立即获得奖励，从而导致更冲动的选择。按顺序 为了将目前的DA功能理论和停止的认知科学联系起来，我们开发了一种新的， 奖励版的SST，评估奖励对进入和停止反应时间的影响程度 背景。这可能被证明对定义DA对行为控制的影响的具体性质至关重要。是这样的 奖励操纵在SST范式中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。额外100名参与者(以及 28名扫描参与者)将完成奖励SST以及一系列自我报告和行为测量 进一步描述这一新范式的冲动。总体而言，这个项目将认知和情感联系在一起 科学和神经科学，行为经济学，神经药理学和人格研究，提供 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.