Neural Mechanisms of Motivated Movement

项目摘要 运动受动机的影响。考虑一个篮球运动员罚球。取决于 赌注的结果的拍摄，性能可以有很大的差异。顶级运动员迎接挑战， 在比赛中比在训练中表现得更好。但是当赌注高得离谱的时候， 当比赛即将开始时，即使是技术娴熟的球员也会“在压力下窒息”，在最重要的时候表现不佳。 动机影响运动表现的神经机制是什么？在这里，我们提出了一个有针对性的 一组实验来剖析动机运动的神经机制。我们的工作是由一个概念性的 这个模型是基于对多巴胺系统功能的数十年研究而建立的。简而言之，我们 多巴胺调节初级运动皮层神经元群的活动。水平 多巴胺是由预期奖励的大小决定的。运动皮层的神经元被多巴胺激活， 以及由意志运动指令。我们假设多巴胺与持续的神经控制相互作用 行为：适量的多巴胺可以提高运动皮层中与运动相关的信号的保真度， 但异常高水平的多巴胺实际上会干扰运动皮层的神经活动模式， 使得它们太易变或结构不良而不能触发成功的运动。如果我们能证明这张照片（或 这样的话，我们就可以第一次在动机和运动之间建立直接的联系。 控制，由参与熟练动作表演的全脑回路介导。 我们的方法依赖于我们最近建立的动物模型：恒河猴表现出相同的行为， 人类的表现。也就是说，随着动机的增加，他们表现出更好的表现， 当风险变得异常高时，他们也会在压力下窒息。据我们所知，这种影响从未 已经在非人类动物身上得到证实，这使得猴子成为我们开始 了解动机和运动在人脑中混合的神经生理学机制。 在这里，使用这个独特的模型，我们首先研究奖励如何调节运动皮层控制运动， 测试几个关于奖励如何调节神经噪声和行为变异性的假设。第二、 我们测试这些奖励相关的调制如何影响的规划，启动和执行的范围。第三、 我们记录中脑多巴胺能奖励处理回路， 多巴胺活动和正在进行的运动表现之间的联系，并探讨皮质多巴胺的因果作用。 我们的研究揭示了运动控制中基于奖励的变化的神经机制，其中有几个 临床意义：（1）在帕金森氏病中，多巴胺能神经元的死亡导致多巴胺能神经元的丧失， 运动活力以及运动质量的下降。这项研究将是第一个将 表明多巴胺活动与动机和运动表现之间存在直接联系。(2)在中风中， 康复可能是一个乏味和令人沮丧的经历。我们的研究表明正确的动机结构 可以改善运动表现，也许还能提高学习能力。(3)我们的工作也与脑机相关 脑机接口（BCI），通过系统的设计，可以提取稳定的电机控制信号，尽管转移， 动机

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.