Cortical and Sub-cortical Contributions to Bimanual Coordination

许多日常活动需要双手的协调运动。例如，当我们拧开瓶盖时，一只手在瓶盖上施加扭矩，而另一只手则稳稳地握住瓶子。握住瓶子的那只手必须精确地补偿另一只手施加的力矩，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，包括用双手用手指和拇指挤压杠杆。在一个任务中，一只手施加的力必须由另一只手来补偿——类似于上面的开瓶例子。在另一项任务中，两只手的相对计时必须精确控制。我们期望在第一个任务中，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；在第二种情况下，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记录，这些区域可能与双手协调有关。在大脑皮层中，我们将重点关注两个运动区域。我们不只是记录任何细胞，而是专门寻找那些向大脑另一侧——皮层或基底神经节——发送投射的神经元。我们将使用刺激模式识别这些细胞，然后观察它们在训练后的双手运动中的放电情况。这是一种强大的方法，因为它允许我们将神经元在完成感兴趣的任务时的自然活动置于它们与另一侧已知的解剖连接的背景下。其次，我们将记录小脑和网状结构的形成。这两个区域对双手控制都很重要。大脑一侧的网状结构向两侧脊髓发送投射物。我们最近的研究表明，小脑也可以影响双侧运动。来自这些区域的记录将表明它们对训练任务所代表的两种类型的手动协调（参数与定时）的相对重要性。最后，我们将记录被认为包含“互神经”的脊髓区域。这些细胞将轴突投射到脊髓的另一侧，并提供一条脊髓通路，通过该通路可以交换信息以协调双手运动。清醒状态下猴子的脊髓记录将被最终麻醉猴子的记录所补充。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，并测量来自脊髓另一侧通过假定的互交神经元间通路的输入。这将提供关于该系统在灵长类动物手部控制中的重要性的详细信息：到目前为止，主要在猫脊髓控制后肢的部分研究了互交中间神经元。这个项目将为大脑如何协调双手运动提供重要的新信息。这一领域之前的大多数研究都使用了对人类行为的观察。之前在训练有素的猴子身上进行的研究研究了大脑皮层中未识别的神经元。该项目将直接记录有代表性的手工任务期间的神经活动。投射穿过中线的皮质神经元子集将被特别针对。它还将记录重要的皮层下和脊髓中枢。这些在讨论双手控制时经常被忽略，主要是因为它们在人类中无法获得非侵入性方法。然而，运动系统是一个分布式系统，所有的运动都是多个相互联系的结构协调作用的结果。在双手控制方面，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是如何实现我们都认为理所当然的精致表现的。

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.