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

描述(由申请人提供)：我们日常生活中的大部分活动都涉及到双手和手臂的运动。在患有颈髓损伤(SCI)的个体中，这种能力在很大程度上被破坏。这项提议有两个主要目标：1)。研究颈椎脊髓损伤患者控制双手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。我们专注于双肘屈伸和精准握法，这是我们日常生活活动中的基本动作。在目标1中，我们将研究运动皮质、皮质脊髓驱动和脊髓在颈椎脊髓损伤后双侧手和手臂运动控制中的作用。经颅磁刺激(TMS)将用于检测皮质内通路和皮质脊髓驱动的兴奋性。脑电(EEG)和肌电(EMG)以及EMG/EMG一致性将被用来检查皮质脊髓传入脊髓运动神经元的传递。我们将使用周围神经刺激来评估运动神经元的兴奋性。总之，这些研究将确定脊髓损伤对参与功能相关动作的生理通路的影响。在目标2中，我们建议研究两种促进上肢运动功能恢复的新方法。首先，我们计划通过使用棘波时序依赖可塑性(STDP)协议来加强皮质脊髓通路中的信息传递。重复的TMS和外周神经刺激对将被精确地定时分别到达运动皮质和脊髓，以诱导突触可塑性。其次，我们计划通过将肌电控制训练与STDP方案相结合，针对受脊髓损伤影响的生理部位(在目标1中确定)，加强对上肢肌肉的自愿控制。训练将包括使用来自双手和手臂肌肉的肌电信号控制2-D光标。该提案中的具体目标将基础科学人类研究和翻译神经科学紧密结合在一起。这项工作将促进我们对双侧动作如何控制的理解，并可能导致新的介入方法的发展，以恢复双侧上肢肌肉的控制。对于脊髓损伤后的手和手臂运动障碍以及其他中枢神经系统疾病缺乏普遍接受的治疗方法，以及目前干预措施对行为的有限改善，突显了这些调查的重要性。

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.