Dopamine Influences on Self-Regulation and Impulsivity

多巴胺对自我调节和冲动的影响

• 批准号: 8333352
• 负责人: DAVID HAROLD ZALD
• 金额: $ 16.74万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-15 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8333352
• 关键词: Adult; Affective; Affinity; Anterior; Area; Attention deficit hyperactivity disorder; Autoreceptors; Behavior; Behavior Control; Behavioral; Binding; Biological Neural Networks; Bipolar Disorder; Brain; Brain region; Clinical Research; Cognitive; Cognitive Science; Corpus striatum structure; Decision Making; Disease; Dopamine; Dopamine D2 Receptor; Economics; Employee Strikes; Functional Magnetic Resonance Imaging; Impulsivity; Individual; Individual Differences; Inferior frontal gyrus; Informal Social Control; Life; Ligands; Link; Measures; Midbrain structure; Modeling; Motivation; Motor; Nature; Neuropharmacology; Neurosciences; Nucleus Accumbens; Participant; Patient Self-Report; Pattern; Performance; Personality; Personality Disorders; Play; Positron-Emission Tomography; Process; Publishing; Reaction Time; Relative (related person); Reporting; Research; Rewards; Rodent; Role; Running; Scanning; Science; Self-control as a personality trait; Signal Transduction; Substance Use Disorder; Task Performances; Techniques; Testing; Time; Translational Research; Validation; Ventral Striatum; Work; base; behavior measurement; blood oxygenation level dependent response; discounting; indexing; neural circuit; neurotransmission; novel; receptor; relating to nervous system; response; theories; young adult

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.

项目摘要 我们最近报告说，中脑多巴胺（DA）自身受体的水平与自我报告成反比 冲动。这一发现表明，DA释放的自动调节控制减少的人是 由于控制与接近相关的动机的能力降低，因此容易受到冲动的影响 由DA神经传递提供。但是，自我报告措施不允许直接检查 行为控制的核心过程被认为是冲动性削弱的。目前，关系 在DA自身受体和冲动性的特定过程之间是未知的，因为冲动是多种多样的 冲动性的构造和行为度量仅与自我报告量表相关。 为了澄清DA功能与冲动性之间的联系，我们建议测量中脑DA自动受体 一组28名健康成年人的冲动性的可用性，行为和fMRI指数。中脑 自身受体的可用性以及纹状体和皮质中的D2样受体的可用性将通过 高亲和力D2/D3配体[18F] Fallypride。所有参与者将完成奖励的停止信号任务 （SST）和时间（延迟）折现（TD）范式，以提供客观的行为度量 控制。 SST和TD范式捕获了冲动的两个不同方面（停止和奖励决策 - 制作），尽管神经网络重叠，但它引起了独特的影响。通过在fMRI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 与自我调节有关的大脑区域（例如，前扣带回，腹侧纹状体，右下角回去）。 我们还将测试目标行为控制区域中的D2受体可用性是否可以预测 任务执行过程中的大胆激活程度，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涉及的区域的参与之间的联系 控制。就TD而言，我们将评估降低自身受体控制导致更大的假设 伏隔核中的大胆反应立即获得奖励，从而导致更加冲动的选择。为了 为了弥合DA功能的当前理论和停止的认知科学，我们开发了一部小说， SST的奖励版本，评估了随之而来的停止反应时间被奖励更改 语境。这对于定义DA对行为控制的影响的特定性质可能是至关重要的。这样的 尽管大多数现实生活 冲动控制问题是在高动力的背景下出现的。另外一百个参与者（以及 28个扫描参与者）将完成奖励的SST和一系列自我报告和行为措施 冲动的进一步表征这种新的范式。总体而言，该项目桥接认知和情感 科学和神经科学，行为经济学，神经药理和人格研究，以提供 理解奖励影响行为控制和自我调节的框架。