Neural Mechanisms of Motivated Movement

动机运动的神经机制

• 批准号: 10608228
• 负责人: Aaron Paul Batista
• 金额: $ 36.28万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-15 至 2028-02-29
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10608228
• 关键词: Affect; Animal Model; Animals; Area; Behavior; Behavior Control; Behavioral; Behavioral Model; Behavioral Paradigm; Belief; Biological Models; Brain; Cessation of life; Choking; Clinical; Cognitive; Coupled; Data Set; Dimensions; Disease; Dopamine; Dopamine Antagonists; Dorsal; Electromyography; Exhibits; Frustration; Goals; Hand; Hemorrhage; Human; Incentives; Infusion procedures; Learning; Link; Macaca mulatta; Manufactured basketball; Mediating; Midbrain structure; Modeling; Monkeys; Motivation; Motor; Motor Cortex; Movement; Muscle; Neurons; Noise; Outcome; Output; Parkinson Disease; Pathway interactions; Pattern; Performance; Persons; Phase; Play; Population; Process; Psychological Theory; Rehabilitation therapy; Research; Rewards; Role; Shapes; Signal Transduction; Stroke; Structure; Subconscious; System; Testing; Time; Uncertainty; Work; addiction; arm; arm movement; behavior influence; brain computer interface; density; design; dopamine system; dopaminergic neuron; driving behavior; experience; experimental study; fascinate; high reward; improved; kinematics; motivated behavior; motor control; motor rehabilitation; neural; neural circuit; neuromechanism; neurophysiology; neuroregulation; neurotransmission; pressure; response; reward anticipation; reward processing; skills

Project Summary Movements are influenced by motivation. Consider a basketball player shooting a free-throw. Depending on the stakes of the outcome of the shot, performance can vary greatly. Top athletes rise to the challenge, and perform better during a game than they do during practice. But when the stakes are inordinately high, like when the game is on the line, even skilled players can “choke under pressure”, and under-perform right when it matters the most. What are the neural mechanisms whereby motivation affects motor performance? Here we propose a targeted set of experiments to dissect the neural mechanisms of motivated movement. Our work is guided by a conceptual model that is premised on decades of research into the function of the dopamine system. Put simply, we posit that dopamine modulates the activity of populations of neurons in the primary motor cortex. The level of dopamine is determined by the size of the expected reward. Neurons in motor cortex are activated by dopamine, as well as by volitional motor commands. We hypothesize that dopamine interacts with the ongoing neural control of behavior: Moderate amounts of dopamine improve the fidelity of movement-related signals in the motor cortex, but unusually high levels of dopamine actually interfere with neural activity patterns in motor cortex, perhaps by making them too variable or poorly-formed to trigger a successful movement. If we can show that this picture (or something like it) is true, then we can, for the first time, establish a direct link between motivation and motor control, mediated by whole-brain circuits involved in the performance of a skilled movement. Our approach relies on our recently established animal model: Rhesus monkeys exhibit the same behavioral performance profile that humans do. That is, they show improved performance as motivation increases, but then when the stakes get unusually high, they also choke under pressure. To our knowledge, this effect has never been demonstrated in a nonhuman animal, which makes monkeys the ideal model system in which we can begin to understand the neurophysiological mechanisms whereby motivation and movement mix in the human brain. Here, using this unique model, we first study how reward modulates the motor cortical control of movement, and test several hypotheses regarding how reward might mediate neural noise and behavioral variability. Second, we test how these reward-related modulations influence the planning, initiation, and execution of reach. Third, we record from midbrain dopaminergic reward processing circuits, to establish moment-by-moment links between dopamine activity and ongoing motor performance, and probe causal effects of cortical dopamine. Our studies stand to unveil the neural mechanisms of reward-based changes in motor control, with several clinical implications: (1) In Parkinson’s disease, the death of dopaminergic neurons results both in a loss of movement vigor and also a degradation in the quality of movement. This study will be among the first that will show a direct link between dopamine activity and both motivation and motor performance. (2) In stroke, rehabilitation can be a tedious and frustrating experience. Our work can show how the right motivational structure can improve motor performance and perhaps learning. (3) Our work also has relevance for brain-computer interfaces (BCI), through the design of systems that can extract stable motor-control signals despite shifts in motivation.

项目摘要 运动受到动力的影响。考虑一名篮球运动员拍摄罚球。取决于 射门结果的取得成果，性能可能差异很大。顶级运动员迎接挑战，并表演 在比赛中比在练习过程中更好。但是，当赌注不高时，就像游戏时 在线上，即使是熟练的球员也可以“在压力下cho缩”，并且在最重要的情况下，表现不佳。 动机会影响运动性能的神经机制是什么？在这里，我们提出了一个目标 一组实验，以剖析动机运动的神经机制。我们的工作以概念为指导 在数十年来研究多巴胺系统功能的模型。简而言之，我们定位 多巴胺调节了原发性运动皮层中神经元种群的活性。水平 多巴胺取决于预期奖励的大小。运动皮质中的神经元被多巴胺激活， 以及通过自愿电机命令。我们假设多巴胺与持续的神经控制相互作用 行为：中等量的多巴胺改善了运动皮层中运动相关信号的保真度， 但是异常高的多巴胺实际上会干扰运动皮层中的神经元活动模式，也许是 使它们太变量或成型不佳，无法触发成功的运动。如果我们可以证明这张图片（或 类似的东西是真实的，那么我们第一次可以建立动机与电动机之间的直接联系 控制，由参与熟练运动表现的全脑电路介导。 我们的方法取决于我们最近建立的动物模型：恒河猴表现出相同的行为 人类具有的性能概况。也就是说，随着动机的增加，它们表现出改善的性能，但是 当赌注很少变高时，它们也会在压力下cho住。据我们所知，这种影响从来没有 在非人类动物中证明，这使猴子成为我们可以开始的理想模型系统 了解神经生理机制，使动机和运动混合在人脑中。 在这里，使用这种独特的模型，我们首先研究了奖励如何调节运动的运动皮质控制，并且 检验几个关于奖励如何介导神经噪声和行为变异性的假设。第二， 我们测试这些与奖励相关的调制如何影响覆盖范围的计划，主动性和执行。第三， 我们从中脑多巴胺能奖励处理电路记录，以建立一时的链接 在多巴胺活性和持续的运动性能以及皮质多巴胺的探针因果作用之间。 我们的研究将揭示运动控制中基于奖励的变化的神经机制，有几个 临床意义：（1）在帕金森氏病中，多巴胺能神经元的死亡都导致失去 运动的活力，也是运动质量的退化。这项研究将是第一个将 在多巴胺活动与动机和运动性能之间显示直接联系。 （2）中风， 康复可能是一次乏味而令人沮丧的经历。我们的工作可以表明正确的动机结构如何 可以改善运动性能甚至学习。 （3）我们的工作也与脑部计算机有关 接口（BCI），通过设计可以提取稳定的电机控制信号目的地的系统设计 动机。