Neural Commands for Fast Movements in the Primate Motor System

快速动作对生存很重要，无论是捕捉猎物还是避免被抓住，还是行人从驶来的汽车面前跳开。在人类运动中，快速的动作是非常重要的。肌肉是由肌肉纤维组成的，这些肌肉纤维在功能上被捆绑成运动单元。每个运动单元都是由一根神经纤维激活的，神经纤维起源于脊髓中的运动神经元细胞。肌肉中通常有几百个运动单元。最近的研究表明，这些与特定肌肉相连的脊髓运动神经元必须在时间上非常紧密地同步激活，以最大限度地提高运动速度。各种不同的大脑和脊髓系统为运动神经元提供驱动其活动的输入。令人惊讶的是，几乎没有测量这些输入是如何在快速运动中被激活的，但现有的数据表明，激活的缓慢增加，与运动神经元的强烈协调和同步放电形成鲜明对比。一个主要的未知是如此紧密的运动神经元同步是如何实现的。在这个提议中，我们将测试运动神经元在被激发(E)以产生快速运动之前被短暂抑制(I)的想法。我们从人类间接测量和计算机模拟中获得的初步证据表明，这种“I-E”激活方案可以通过提供更好的运动神经元同步来提高运动速度。我们将使用健康的人类受试者和清醒的猴子的记录来测试这个想法。这将为神经回路功能和抑制作用提供理论见解，并在实践中帮助我们了解健康和疾病中速度表现的限制。在人类身上，我们将使用放置在肌肉内的精细电极，以及覆盖在肌肉上的皮肤表面网格电极，来记录肌肉活动。我们将使用数学方法将多通道记录分离成单个运动单元的活动模式。我们将对这些进行分析，以寻找最初的抑制加速运动的证据。我们还将要求受试者进行为期4周的训练以提高速度，并测量这如何改变运动神经元激活的时间。猴子将接受训练，根据电脑屏幕上的听觉和视觉指令做出快速动作。我们将使用表面网格电极记录运动单元的活动，就像在人类身上一样。此外，我们将在运动皮层、网状结构和脊髓这三个产生输入以激活运动神经元的重要中心，插入具有1024个紧密间隔记录位点的神经探针。我们将把一些用于肌肉记录的分析方法扩展到这些神经记录。这将使我们能够同时解析许多神经元的活动。使用数学方法观察一个细胞的活动如何影响另一个细胞的活动，我们将识别局部细胞之间的联系，以及与运动神经元的联系。这种方法还允许我们区分抑制性细胞和兴奋性细胞。我们将使用这些录音来寻找“I-E”驱动的证据，包括从运动神经元到中枢神经系统的一部分到另一部分（例如从皮层到脑干）。最后，我们将利用这个丰富的数据集来量化快速运动过程中运动神经元输入的皮层、脑干和脊髓来源的相对重要性。该项目将使用最近才可用的技术，为我们理解人类/动物性能极限下的运动控制提供基础知识。成功可以帮助我们提高个人的表现，例如在运动中，或者在运动系统受损或随着年龄的增长而发现自己的运动变慢的病人身上。在一个理想的系统中，对“I-E”驱动特性的进一步了解，可能会揭示更普遍和跨物种的神经通信的新原理。

Fast movements are important for survival, whether it be catching prey or avoiding being caught, or a pedestrian jumping out of the way of an approaching car. Fast movements are much prized in human sports. Muscles are made up of muscle fibres, which are bundled functionally into motor units. Each motor unit is activated by a single nerve fibre, which originates from a motoneuron cell in the spinal cord. There are typically several hundred motor units in a muscle. Recent work suggests that these spinal motoneurons connected to a given muscle must be activated very closely synchronised in time to maximise movement speed. Various different brain and spinal cord systems provide inputs to motoneurons which drive their activity. Surprisingly, there are few measurements of how these inputs are activated during fast movements, but the available data suggests a sluggish increase in activation, in marked contrast to the sharply coordinated and synchronous firing of motoneurons. A major unknown is how such tight motoneuron synchrony is achieved. In this proposal, we will test the idea that motoneurons are transiently inhibited (I), before being excited (E) to generate fast movement. Our preliminary evidence, from indirect measures in humans and computer modelling, suggests that this 'I-E' activation scheme could increase movement speed by providing better motoneuron synchronisation. We will test this idea using recordings from healthy human subjects and awake behaving monkeys. This will provide theoretical insights into neural circuit function and the role of inhibition, and practically will help us to understand limits to speed performance in health and disease.In humans, we will use fine electrodes placed within a muscle, and surface grid electrodes on the skin overlying a muscle, to record muscle activity. We will use mathematical methods to separate the multi-channel recordings into the activity patterns of single motor units. We will analyse these to look for evidence that initial inhibition speeds up movement. We will also ask subjects to undertake a 4-week period of training to increase speed, and measure how this changes the timing of motoneuron activation.Monkeys will be trained to perform fast movements in response to auditory and visual instruction on a computer screen. We will record motor unit activity using surface grid electrodes, just as in humans. In addition, we will insert neural probes with 1024 closely-spaced recording sites into the motor cortex, reticular formation and spinal cord - three important centres which generate the input to activate motoneurons. We will extend some of the analysis methods developed for recordings from muscle to these neural recordings. This will allow us to resolve activity from many neurons simultaneously. Using mathematical methods which look at how the activity of one cell influences the activity of another, we will identify connections between cells locally, and to motoneurons. This approach also permits us to distinguish inhibitory from excitatory cells. We will use these recordings to search for evidence of 'I-E' drive, both to motoneurons and from one part of the central nervous system to another (e.g. from the cortex to the brainstem). Finally, we will exploit this rich dataset to quantify the relative importance of cortical, brainstem and spinal sources of motoneuron input during fast movement.This project will provide fundamental knowledge underpinning our understanding of motor control at the limit of human/animal performance, using technologies which have only recently become available. Success may help us to improve individual performance, e.g. in sport, or in patients who find that their movements are slowed after damage to the motor system or with ageing. Increased understanding of the properties of 'I-E' drive, in a system ideally suited to dissect this, may reveal novel principles of neural communication applicable more generally and across species.