Physiological and functional interactions between cortical and subcortical structures in skilled hand movements

抓取和操纵物体以及使用工具都是我们日常执行的重要的熟练手部功能。我们通常认为这些技能，如写作和饮食，是理所当然的。当然，这是直到受伤或疾病阻止我们进行这些活动。手功能的缺陷会对最简单的任务产生巨大的影响。康复干预已被证明对改善手功能有用，但其益处仍然有限。作为熟练抓握基础的大脑和脊髓生理机制是复杂的，并且仍然没有被很好地理解。研究这些机制以及它们之间的相互作用将有助于我们更好地了解健康和疾病中的中枢神经系统。本提案的第一个目的是研究大脑中参与物体抓握的特定区域（称为运动前皮质）如何与脊髓内的回路相互作用。对猴子的研究已经表明，从大脑到脊髓有直接和间接的通路。然而，这些连接是否存在，是否在人体内起作用，还不得而知。因此，使用非侵入性的磁和电刺激技术，我们将研究运动前皮层如何在休息时和熟练抓握期间（例如，精确抓握-将物体保持在食指和拇指之间）与两个脊髓回路相互作用。第一个是一个简单的脊髓反射回路，第二个是一个更复杂的脊髓神经元系统，被认为可以重塑从大脑到手臂肌肉的信号，称为propriospinal系统。这些实验将验证运动前区皮层和支配手部肌肉的不同脊髓回路之间是否存在直接和/或间接的相互作用。然而，由于这种脊髓回路在通往肌肉的途中重塑了大脑信号，当抓握过程中发生意外的内部或外部变化时，它可能会发挥特别重要的作用。在这种情况下，propriospinal系统以前没有测试过，因此，本建议的第二个目的是检查propriospinal系统的贡献，在抓任务的意外变化。同样，我们将在两个任务中应用非侵入性磁刺激和电刺激。第一项任务将测试当一个意外重量的物体被抓住时，本体脊髓系统是如何受到影响的。第二个任务将测试当物体的重量在抓握之前改变时，本体脊髓系统是如何受到影响的。这些实验将使我们能够确定在熟练抓握过程中，本体脊髓系统何时以及在何种意想不到的情况下发挥作用，这项工作有可能有益于运动障碍的研究和临床应用。了解运动前区和脊髓之间的相互作用可以为刺激方案提供替代的潜在目标，这些刺激方案旨在增加脑或脊髓的活动，并最终改善中风或脊髓损伤后的手部运动功能。非人类灵长类动物的研究已经显示了脊髓损伤后本体脊髓系统的重要性，因此如何促进该系统的知识在康复策略中可能很重要。最后，这项工作的发现可以改进软件和机器人手和假肢的设计，用于瘫痪或肢体缺失的人抓握。

Grasping and manipulating objects and using tools are all important skilled hand functions that we perform on a daily basis. Often we take these skills, such as writing and eating, for granted. This is of course until injury or disease prevents us from performing such activities. Deficits in hand function can have tremendous effects on the simplest of tasks. Rehabilitative interventions have proved useful for the improvement of hand function, but their benefits remain limited. Brain and spinal cord physiological mechanisms that underlie skilled grasping are complex and still are not well understood. Investigating these mechanisms and how they interact with one another will help us better understand the central nervous system in health and disease.The first aim of this proposal is to investigate how particular areas of the brain involved in the grasping of objects, known as the premotor cortex, interact with circuits within the spinal cord. Research in monkeys has already shown that there are direct and indirect pathways from the brain to the spinal cord. Yet, whether these connections exist and are functional within the human is unknown. Therefore, using non-invasive magnetic and electrical stimulation techniques we will investigate how the premotor cortex interacts with two spinal cord circuits at rest and during skilled grasp (e.g. a precision grip - holding an object between the index finger and thumb). The first is a simple spinal reflex circuit and the second is a more complex system of spinal neurons that is thought to reshape signals from the brain on their way down to arm muscles, known as the propriospinal system. These experiments will characterise whether there are direct and/or indirect interactions between the premotor cortex and different spinal cord circuitry that innervate hand muscles.Previous work investigating the propriospinal system's involvement in skilled grasping has yielded conflicting results. Yet, as this spinal circuit reshapes brain signals on their way to muscles it could play a particularly important role when unexpected internal or external changes occur during grasping. The propriospinal system has not been previously tested under these circumstances, therefore the second aim of this proposal is to examine the propriospinal system's contribution to unexpected changes during a grasping task. Again, we will apply non-invasive magnetic and electrical stimulation during two tasks. The first task will test how the propriospinal system is affected when an object of an unexpected weight is grasped. The second task will test how the propriospinal system is affected when the weight of an object is changed prior to grasping. These experiments will allow us to characterise when and during what unexpected circumstances the propriospinal system comes into play during skilled grasping.This work has the potential to benefit research and clinical applications in motor disorders. Understanding the interactions between premotor areas and the spinal cord could provide alternative potential targets for stimulation protocols that are designed to increase activity in the brain or spinal cord, and ultimately improve hand motor function, after stroke or spinal cord injury. Non-human primate research has already shown the importance of the propriospinal system after spinal cord injury, so knowledge of how to facilitate this system could be important in rehabilitation strategies. Finally, the findings of this work could improve the design of software and robotic hands and prosthesis used for grasping for people with paralysed or absent limbs.