Dopaminergic Mechanisms Underlying Human Social Behavior: A Multimodal Approach

人类社会行为背后的多巴胺能机制：多模式方法

• 批准号: 10368924
• 负责人: Ming Hsu
• 金额: $ 67.81万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-03-05 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10368924
• 关键词: Adult; Animal Model; Behavior; Behavior Disorders; Behavioral; Behavioral Model; Biological Markers; Brain; Brain region; Cognition; Cognitive; Computer Models; Corpus striatum structure; Data; Decision Making; Development; Dopamine; Dopamine D2 Receptor; Economic Models; Economics; FDA approved; Functional Magnetic Resonance Imaging; Human; Individual Differences; Intervention; Knowledge; Learning; Legal patent; Link; Literature; Measures; Medial; Memory; Mental disorders; Metabolism; Methods; Modeling; Molecular; Motor; Nature; Neuromodulator; Neurotransmitters; Participant; Pharmaceutical Preparations; Pharmacology; Placebos; Play; Positron-Emission Tomography; Process; Psychological reinforcement; Psychopharmacology; Race; Research Personnel; Rewards; Role; Schizophrenia; Signal Transduction; Social Behavior; Social Class; Social Environment; Social Functioning; Social Perception; Stimulus; Symptoms; System; Testing; Therapeutic; Translating; Variant; addiction; base; behavior measurement; behavior observation; behavioral economics; behavioral pharmacology; cognitive neuroscience; cognitive process; emotional functioning; experience; experimental study; inhibitor; insight; interdisciplinary approach; multidisciplinary; multimodality; neural circuit; neural correlate; neurochemistry; neuroeconomics; neuroimaging; neuromechanism; neuropsychiatric disorder; patient population; relating to nervous system; social; social cognition; social deficits; social influence; social learning; theories; tolcapone; tool

PROJECT SUMMARY A significant challenge for understanding social dysfunctions observed in mental illness is to link high-level theories of social behavior and cognition with the computations performed by brain circuits. Specifically, how does the brain translate social perception into social valuation, and how does such valuation influence social actions? We propose to leverage recent developments in economic theory and cognitive neuroscience to bridge this divide using a computational, model-based approach. In this proposal, we hypothesize that social behavior is underpinned by brain mechanisms that are influenced by the neurotransmitter dopamine, and that these mechanisms can be captured by computational models that integrate internal representations of social experience, and parameters relevant to dopamine tone, to inform social actions. Social valuation thus critically, and quantitatively, depends upon both internal social representations and the neurochemistry of the actor within the social environment. To assess this hypothesis, we pursue two approaches to evaluate dopamine tone: one in which we use an FDA-approved medication, tolcapone, to influence dopamine metabolism, and one in which we perform PET imaging to measure dopamine release and baseline dopamine receptor D2/D3 occupancy. We then apply a model of social valuation to subjects' behavior, and search for neural correlates of this valuation using functional MRI (fMRI). To this end, we bring together a group of experts in (1) the neuroeconomics and modeling of social and non-social decision-making, (2) cognitive neuroscience, (3) the pharmacology of frontostriatal circuits, and (4) neuroimaging. We thus seek to broaden our understanding of the computations and circuits underlying social behavior. Moreover, we believe that a model-based understanding of these behaviors and neural circuits may guide more robust predictions of the effects of pharmacological manipulations on social valuation, and provide quantitative tools to assess the effects of such manipulations in patient populations, with possible therapeutic implications.

项目摘要 理解在精神疾病中观察到的社会功能障碍的一个重大挑战是将高水平的 社会行为和认知的理论与大脑回路的计算。具体到如何 大脑是否将社会感知转化为社会评价，以及这种评价如何影响社会 行动？我们建议利用经济理论和认知神经科学的最新发展， 使用基于模型的计算方法来弥合这一鸿沟。在这份提案中，我们假设社会 行为是由受神经递质多巴胺影响的大脑机制支撑的， 这些机制可以通过计算模型来捕获， 经验，以及与多巴胺张力相关的参数，以告知社会行为。社会评价因此 关键的，定量的，取决于内部的社会表征和神经化学的， 社会环境中的演员。为了评估这一假设，我们采用两种方法来评估 多巴胺张力：我们使用FDA批准的药物托卡朋来影响多巴胺。 其中一个是我们进行PET成像来测量多巴胺的释放和基线多巴胺 受体D2/D3占有率。然后，我们将社会评价模型应用于受试者的行为，并寻找 使用功能性MRI（fMRI）评估神经相关性。为此，我们召集了一群 专家在（1）神经经济学和社会和非社会决策建模，（2）认知 神经科学，（3）额纹状体回路药理学，（4）神经影像学。因此，我们寻求扩大 我们对社会行为背后的计算和电路的理解。此外，我们认为， 对这些行为和神经回路的基于模型的理解可以指导对这些行为的更鲁棒的预测。 药理学操作对社会评价的影响，并提供定量工具来评估 这种操作在患者群体中的影响，可能具有治疗意义。