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

抓握和操纵物体以及使用工具都是我们日常生活中重要的熟练手功能。我们常常把这些技能，如写作和饮食，视为理所当然。当然，这是在受伤或疾病阻止我们进行这些活动之前。手部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。大脑和脊髓的生理机制，在熟练抓取是复杂的，仍然没有很好地理解。研究这些机制以及它们如何相互作用将有助于我们更好地了解中枢神经系统在健康和疾病中的作用。这项提议的第一个目的是研究大脑中参与抓取物体的特定区域，即所谓的运动前皮层，是如何与脊髓内的回路相互作用的。对猴子的研究已经表明，从大脑到脊髓有直接和间接的途径。然而，这些联系是否存在并在人体内发挥作用尚不清楚。因此，使用非侵入性磁刺激和电刺激技术，我们将研究运动前皮层在休息和熟练抓取（例如精确抓取-食指和拇指之间握住物体）时如何与两个脊髓回路相互作用。第一个是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，被认为是在大脑信号传递到手臂肌肉的过程中重塑来自大脑的信号，被称为本体脊髓系统。这些实验将描述运动前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。先前研究本体神经系统参与熟练抓取的工作产生了相互矛盾的结果。然而，由于这种脊髓回路在传递给肌肉的过程中重塑了大脑信号，当抓取过程中发生意想不到的内部或外部变化时，它可能会发挥特别重要的作用。本体系统以前没有在这些情况下进行过测试，因此本提案的第二个目的是检查本体系统对抓取任务期间意外变化的贡献。同样，我们将在两个任务中应用非侵入性磁刺激和电刺激。第一个任务将测试当一个意外重量的物体被抓住时，本体神经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取之前发生变化时，本体神经系统是如何受到影响的。这些实验将使我们能够描述在什么时候以及在什么意想不到的情况下，本体神经系统在熟练抓取中发挥作用。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表明了脊髓损伤后本体系统的重要性，因此如何促进该系统的知识在康复策略中可能是重要的。最后，这项工作的发现可以改进软件和机械手的设计，以及用于抓取瘫痪或缺肢的人的假肢。

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.