Cortical and Sub-cortical Contributions to Bimanual Coordination

许多日常动作都需要两只手协调运动。例如，当我们拧开瓶盖时，一只手对瓶盖施加扭矩，另一只手稳住瓶子。握住的手必须精确地补偿另一只手施加的扭矩，否则瓶子就会打滑。在这个项目中，我们将研究双手协调的神经系统。猕猴将接受两项任务的训练，包括用双手在手指和拇指之间挤压杠杆。在一项任务中，一只手施加的力必须由另一只手补偿--类似于上面的开瓶例子。在另一项任务中，必须精确控制两只手的相对定时。我们预计，在第一个任务中，控制每只手的神经系统将交换有关运动参数(力的水平)的信息；在第二个任务中，它们将交换计时信息。然后，我们将从神经系统的多个区域进行录音，这些区域可能涉及双手协调。在大脑皮层，我们将关注两个运动区。不只是记录任何细胞，我们将专门搜索将投射发送到大脑另一边的神经元-要么发送到皮质，要么发送到基底节。我们将使用刺激范式识别这些细胞，然后观察它们在训练的双手动作中的激活情况。这是一种强大的方法，因为它允许我们将感兴趣的任务期间神经元的自然活动置于它们与对侧的已知解剖联系的背景下。其次，我们将从小脑和网状结构记录。这两个区域对双工控制都很重要。大脑一侧的网状结构将投射发送到脊髓的两侧。我们最近发现，小脑也可以影响双侧的运动。来自这些区域的记录将表明它们对于训练任务所代表的两种类型的双手协调(参数与定时)的相对重要性。最后，我们将从脊髓中据信含有“连合神经元间”的区域进行记录。这些细胞将轴突投射发送到脊髓的另一侧，并提供一条脊髓路径，通过该路径可以交换信息，以协调双手运动。清醒的猴子的脊椎录音将被终末麻醉的猴子的录音所补充。在这些实验中，我们将记录控制肌肉(运动神经元)的脊髓细胞，并通过假定的神经元间连合通路测量来自脊髓另一侧的输入。这将为这个系统在控制灵长类动物手中的重要性提供详细的信息：到目前为止，对连合中间神经元的研究主要集中在猫脊髓中控制后肢的部分。这个项目将提供有关大脑如何双眼协调运动的重要新信息。在这一领域之前的大多数研究都使用了对人类的行为观察。之前在经过训练的猴子身上所做的工作已经对大脑皮层中的不明神经元进行了研究。该项目将在典型的双工任务中直接记录神经活动。横跨中线投射的皮质神经元的子集将成为特定的目标。它还将从重要的皮质下和脊髓中心进行记录。在讨论双手控制时，这些经常被忽略，主要是因为它们不能用于人类的非侵入性方法。然而，电机系统是一个分布式系统，所有的运动都是多个相互关联的结构协调作用的结果。在双手控制中，就像在运动控制的其他领域一样，除非我们研究所有的组成系统，否则我们将无法理解大脑如何实现我们都认为理所当然的精致表现。

Many everyday actions require coordinated movement of the two hands. For example, when we unscrew the top of a bottle, one hand exerts torques on the cap whilst the other holds the bottle steady. The holding hand must precisely compensate for the torques imposed by the other hand, otherwise the bottle will slip. In this project, we will investigate the neural systems underlying bimanual coordination. Macaque monkeys will be trained on two tasks, involving squeezing levers between finger and thumb with both hands. In one task, forces exerted by one hand must be compensated by the other - similar to the bottle opening example above. In the other task, the relative timing of the two hands must be precisely controlled. We expect that in the first task, neural systems controlling each hand will exchange information about movement parameters (level of force); in the second, they will exchange timing information. We will then make recordings from multiple regions of the nervous system which could be involved in bimanual coordination. In the cerebral cortex, we will focus on two motor regions. Rather than just recording any cells, we will search specifically for neurons which send projections to the other side of the brain - either to the cortex, or to the basal ganglia. We will identify these cells using a stimulation paradigm, and then observe their firing during the trained bimanual movements. This is a powerful approach, as it allows us to place the natural activity of the neurons during tasks of interest in the context of their known anatomical connections with the opposite side. Secondly, we will record from the cerebellum and reticular formation. Both regions are important for bimanual control. The reticular formation on one side of the brain sends projections to both sides of the spinal cord. We have recently shown that the cerebellum can also influence movements bilaterally. Recording from these regions will indicate their relative importance for the two types of bimanual coordination (parametric vs timing) represented by the trained tasks. Finally, we will record from the region of the spinal cord believed to contain 'commisural interneurones'. These cells send axonal projections to the other side of the cord, and provide a spinal pathway by which information could be exchanged for the coordination of bimanual movement. The spinal recordings in awake behaving monkeys will be supplemented by recordings in terminally anaesthetised monkeys. In these experiments, we will record from the spinal cells which control muscles (motoneurons), and measure the inputs from the other side of the cord via presumed commissural interneuron pathways. This will provide detailed information about the importance of this system in the control of the primate hand: until now, commissural interneurons have been investigated mainly in the part of the cat spinal cord which controls the hind limb. This project will provide important new information on how the brain coordinates movements bimanually. Most previous studies in this field have used behavioural observations in humans. Previous work in trained monkeys has investigated unidentified neurons in the cerebral cortex. This project will record neural activity directly, during representative bimanual tasks. The subset of cortical neurons which project across the midline will be specifically targeted. It will also record from important sub-cortical and spinal centres. These are often ignored in discussions of bimanual control, mainly because of their inaccessibility to non-invasive methods in man. Yet the motor system is a distributed system, and all movements result from the coordinated action of multiple interconnected structures. In bimanual control, as in other areas of motor control, we will not understand how the brain achieves the exquisite performance which we all take for granted unless we investigate all the component systems.