Neural Control of Bilateral Hand and Arm Movements After Spinal Cord Injury

描述（由申请人提供）：我们的日常生活活动大多涉及双手和手臂的运动。颈脊髓损伤（SCI）患者的这种能力在很大程度上受到破坏。该提案有两个主要目标：1）。检查有助于控制颈脊髓损伤患者双侧手部和手臂运动的中枢神经系统通路的生理学，以及2）。研究促进上肢运动功能恢复的方法。我们专注于双侧肘关节屈曲/伸展和精确抓握，这是我们日常生活活动中的基本动作。在目标1中，我们将研究运动皮层、皮质脊髓驱动和脊髓对颈脊髓损伤后双侧手和手臂运动控制的作用。经颅磁刺激（TMS）将用于检查皮质内通路和皮质脊髓驱动的兴奋性。将使用脑电图（EEG）和肌电图（EMG）以及EMG/EMG相干性来检查皮质脊髓输入到脊髓运动神经元的传输。我们将通过外周神经刺激来评估运动神经元的兴奋性。总之，这些研究将确定SCI对参与功能相关行动的生理途径的影响。在目标2中，我们提出研究两种新的方法来促进上肢运动功能的恢复。首先，我们计划通过使用尖峰时间依赖可塑性（STDP）协议来加强皮质脊髓通路中的传输。TMS和外周神经刺激的重复对将被精确地定时以分别到达运动皮层和脊髓，以诱导突触可塑性。其次，我们计划通过结合肌电控制训练和STDP协议，针对受SCI影响的生理部位（目标1中确定），增强上肢肌肉的自主控制。训练将包括使用来自双侧手部和手臂肌肉的EMG信号控制2-D光标。该提案中的具体目标将基础科学人类研究和转化神经科学紧密结合在一起。这项工作将推进我们对双侧动作是如何控制的理解，并可能导致开发新的干预方法来恢复上肢肌肉的双侧控制。SCI后手和手臂运动障碍和其他CNS疾病缺乏普遍接受的治疗方法，以及目前干预措施的有限行为改善突出了这些研究的重要性。

DESCRIPTION (provided by applicant): Most of our daily life activities involve bilateral hand and arm movements. This ability is largely disrupted in individuals with cervical spinal cord injury (SCI). This proposal has two main goals: 1). examine the physiology of CNS pathways contributing to the control of bilateral hand and arm movements in individuals with cervical SCI, and 2). study approaches to promote recovery of upper-limb motor function. We focus on bilateral elbow flexion/extension and precision grip, which are basic movements in our daily life activities. In Aim 1, we will examine the contribution of the motor cortex, corticospinal drive, and spinal cord to the control of bilateral hand and arm movements after cervical SCI. Transcranial magnetic stimulation (TMS) will be used to examine excitability of intracortical pathways and corticospinal drive. Electroencephalography (EEG) and electromyography (EMG) and EMG/EMG coherence will be used to examine transmission in corticospinal inputs to spinal motoneurons. We will assess motoneuronal excitability by using peripheral nerve stimulation. Together, these studies will identify the effects of SCI on physiological pathways involved in functionally relevant actions. In Aim 2, we propose to study two novel approaches to promote recovery of upper-limb motor function. First, we plan to strengthen transmission in the corticospinal pathway by using spike-timing- dependent plasticity (STDP) protocols. Repeated pairs of TMS and peripheral nerve stimuli will be precisely timed to arrive at the motor cortex and spinal cord, respectively, to induce synaptic plasticity. Second, we plan to enhance voluntary control of upper-limb muscles by combining myoelectric-controlled training with STDP protocols, targeting physiological sites affected by SCI (identified in Aim 1). Training will consist of controlling a 2-D cursor using EMG signals from bilateral hand and arm muscles. The specific Aims in this proposal tightly couple basic scientific human research and translational neuroscience. This work will advance our understanding of how bilateral actions are controlled and could lead to the development of novel interventional approaches to restore bilateral control of upper-limb muscles. The absence of universally accepted treatments for hand and arm motor disability after SCI, and other CNS disorders, and the limited behavioral improvements with present interventions highlight the importance of these investigations.