Neural Mechanisms of Motivated Movement

项目摘要 动作受动机的影响。想一想一个篮球运动员罚球的情形。取决于 投篮结果的利害关系，表现可以有很大的差异。顶尖运动员迎接挑战，表现出色 在比赛中比在练习中做得更好。但当赌注高得离谱时，比如比赛 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。 动机影响运动性能的神经机制是什么？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 这一模型的前提是数十年来对多巴胺系统功能的研究。简而言之，我们假设 多巴胺调节初级运动皮质神经元群体的活动。的水平 多巴胺由预期回报的大小决定。运动皮质中的神经元被多巴胺激活， 以及通过意志力马达命令。我们假设多巴胺与正在进行的神经控制相互作用 行为：适量的多巴胺提高了运动相关信号在运动皮质中的保真度， 但异常高的多巴胺水平实际上干扰了运动皮质的神经活动模式，可能是通过 使它们过于多变或形状不佳，不能触发成功的动作。如果我们能证明这张照片(或 类似的东西)是真的，那么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，由全脑回路调节，参与熟练动作的执行。 我们的方法依赖于我们最近建立的动物模型：恒河猴表现出同样的行为 人类所做的性能分析。也就是说，随着动机的增强，他们表现出更好的表现，但随后 当赌注变得异常高时，他们也会在压力下窒息。据我们所知，这种影响从来没有 已经在非人类动物身上进行了演示，这使得猴子成为我们可以开始研究的理想模型系统 了解人类大脑中动机和运动混合的神经生理学机制。 在这里，利用这个独特的模型，我们首先研究了奖赏如何调节运动的运动皮质控制，以及 测试几个关于奖励可能如何调节神经噪音和行为变异性的假设。第二, 我们测试了这些与奖励相关的调节如何影响REACH的计划、启动和执行。第三, 我们记录来自中脑的多巴胺能奖赏处理电路，以建立每时每刻的联系 多巴胺活动和持续运动表现之间的关系，以及探索皮质多巴胺的因果效应。 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)在帕金森病中，多巴胺能神经元的死亡导致 运动的活力和运动质量的下降。这项研究将是第一批 显示多巴胺活动与动机和运动表现之间的直接联系。(2)卒中时， 康复可能是一种乏味和令人沮丧的经历。我们的工作可以表明，正确的激励结构 可以提高运动能力，也许还能提高学习能力。(3)我们的工作也与脑-计算机有关 接口(BCI)，通过设计的系统可以提取稳定的电机控制信号，即使在 动力。

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.