Two Types of Grasp: Dissecting Cortical and Sub-cortical Contributions to Primate Hand Function

灵长类动物的手是一个高度通用的致动器，能够灵活地重新配置，以实现任务目标。这与低等哺乳动物的爪子非常不同，后者的能力仅限于全手抓握。有一些证据表明，灵长类动物可能保留了更原始的抓握能力，以及灵巧手功能的进化发展。这表明手可以在两种模式下操作。其中一种是手指弯曲或伸展在一起以抓住物体（动力握法）。在另一种模式下，单个手指可以独立控制，以产生任意手势或复杂的抓握，例如精确（捏）抓握。我们认为这些模式是由大脑和脊髓内不同的控制回路支撑的。虽然对运动神经控制的基础科学很感兴趣，但这个想法在从中风或脊髓损伤等损伤中恢复的患者中变得特别重要。然后，精确抓握网络的关键组成部分似乎丢失了;恢复仅限于粗略的抓握。手变成了爪子。在这个建议中，我们将确定哪些神经回路有助于不同类型的手使用，使用与人类手功能非常相似的猕猴。我们将首先训练猴子进行力量抓握，精确抓握和单独的食指运动。使用精细的微电极，我们将记录运动和前运动皮层、脑干和脊髓在不同手部动作过程中的神经活动。通过测量执行任务时细胞活动的变化，我们将能够分辨出哪些区域对每种手部操作模式起作用。在某些治疗过程中，我们会向某个区域注射微量的药物，以使其安静下来。观察所产生的手部缺陷类型，将确认每个区域所扮演的角色。做出任何动作的命令都来自大脑皮层，必须传递到较低的中枢，才能执行。在第二个使用麻醉猴子的系列实验中，我们将在皮质的运动和前运动区放置刺激电极，并测量皮质刺激后脑干和脊髓中的细胞反应。这将告诉我们皮层如何将指令传达给皮层下结构。在人类中，可以使用经颅磁脑刺激（TMS）无创地激活皮质输出。如果我们改变线圈在头部的固定方式，TMS似乎会以不同的方式刺激大脑，但我们不知道在不同的条件下会激活什么。我们将通过在麻醉的猴子中使用TMS来解决这个问题，告诉我们TMS是否可以根据线圈的方向选择性地访问电路以获得电力和精确的抓握。最后，我们将测试不同区域的细胞如何对皮肤和肌肉中的感觉受体的刺激做出反应。在人类研究中，我们将应用所获得的知识，使用不同方向的TMS结合感觉刺激来探测力量和精确抓握网络的特定组件。在对健康受试者进行验证后，我们将把这些方法应用于脊髓损伤康复者，从而展示各种回路如何重新配置以介导恢复。这项工作将揭示有关人类手部功能控制及其损伤后恢复的核心信息。这个基础是需要开发新的，原则性的方法来掌握康复。由于手是日常生活活动的核心，即使是未来功能的微小改善也可能对减轻残疾和提高生活质量产生重大影响。

The primate hand is a highly versatile actuator, capable of flexible reconfiguration to achieve task goals. This is very different from the paw of lower mammals, which has a capability restricted to whole-hand grasp. There is some evidence that primates may have retained capacities for more primitive grasp, alongside the evolutionary development of dexterous hand function. This suggests that the hand can operate in two modes. In one, the fingers flex or extend together to grasp an object (the power grip). In the other mode, single fingers can be independently controlled, to produce arbitrary gestures or complex grasps exemplified by the precision (pinch) grip. We propose that these modes are underpinned by different control circuits within the brain and spinal cord. Whilst interesting to the basic science of the neural control of movement, this idea becomes especially important in patients who are recovering from damage such as after stroke or spinal cord injury. Then, key components of the precision grip network seem to be lost; recovery is limited to gross grasp. The hand becomes a paw.In this proposal, we will determine which neural circuits contribute to the different types of hand use, using macaque monkeys which have very similar hand function to humans. We will first train monkeys to perform power grip, precision grip and an isolated index finger movement. Using fine microelectrodes, we will then record neural activity from the motor and pre-motor cortex, brainstem and spinal cord during performance of the different hand movements. By measuring the changes in cell activity as the tasks are carried out, we will be able to tell which areas contribute to each mode of hand operation. In some sessions, we will inject tiny quantities of a drug into an area to silence it; observing the types of hand deficits produced will confirm the role each area plays.Commands to make any movement originate in the cerebral cortex, and must be transmitted to lower centres to allow them to be executed. In a second series of experiments using anaesthetised monkeys, we will place stimulating electrodes in the motor and pre-motor areas of the cortex, and measure cell responses in the brainstem and spinal cord following cortical stimulation. This will tell us how the cortex communicates its instructions to sub-cortical structures. In humans, it is possible to activate cortical outputs non-invasively using transcranial magnetic brain stimulation (TMS). If we change how the coil is held on the head, TMS seems to stimulate the brain differently, but we don't know what is activated in the various conditions. We will address this by also using TMS in the anaesthetised monkeys, to tell us if TMS can selectively access the circuits for power and precision grips depending on how the coil is oriented. Finally, we will test how cells in the various areas respond to stimulation of the sensory receptors in skin and muscle.In studies in humans, we will apply the knowledge gained, using TMS in different orientations combined with sensory stimuli to probe specific components of the power and precision grip networks. After validating the methods in healthy human subjects, we will apply them to individuals who have recovered from spinal cord injury, thereby showing how the various circuits reconfigure to mediate recovery.This work will reveal core information about the control of human hand function and its recovery after damage. This foundation is required to develop novel, principled approaches to grasp rehabilitation. As the hand is so central to activities of daily living, even small future improvements in function could have major impacts in alleviating disability and raising quality of life.