Strengthening task specific activation of paretic hand muscles after moderate-to-severe chronic stroke

摘要 在美国每年遭受中风的80万人中，高达65%的人继续经历着MOD- 一只手在六个月或更长时间内出现从严重到严重的损伤，限制了他们执行日常任务的能力。这些损伤， 通常以功能受限的手腕和手指伸展为特征(&lt；20°)，防止瘫痪的手在功能障碍中的使用。 有选择性的任务。功能性电刺激(FES)，常用于促进瘫痪手在功能上的重复使用。 传统任务，在这一人群中表现出温和而短暂的影响。神经调节的几种非侵入性方法 [例如，重复经颅磁刺激(RTMS)、经颅直流电刺激或成对联合刺激- 也被应用于与中风相同半球或对侧的皮质运动区，以 增强FES促进的特定任务实践的效果。然而，支持这种有效性的证据有限。 这些方法中的一种。因此，研究改善手功能和功能指数的替代方法是至关重要的。 在这个更受伤害的人群中存在悬念。我们的长远目标是发展机械化和理论驱动的康复- 改善严重中风患者手功能和功能独立性的干预措施。这个 皮质脊髓轴突和脊髓运动神经元之间的突触连接强度--这一点受到严重影响 中风后-是产生功能相关的自主性运动的关键。新出现的证据表明， 用于重组脊髓运动神经元池上残留的皮质脊髓输入，以支持中风后的康复。成对的 皮质脊髓运动神经元刺激(PCMS)被证明可以加强存活的皮质脊髓-运动神经元之间的突触。 Nal轴突和脊髓运动神经元。在PCMS中，TMS与周围神经刺激(PNS)配对，从而使TMS- 诱发的皮质脊髓痉挛到达皮质脊髓运动神经元突触前约1-2毫秒 经三叉神经节的脊髓运动神经元。先前对不完全性脊髓损伤患者的研究表明，PCMS 在自愿收缩期间分娩可在皮质脊髓传递(即诱发的运动大小)方面获得更大的收益 潜能值[MEP])而不是静止状态。皮质脊髓传递的这些改善也与改善有关。 在手功能方面，表明PCMS期间的自愿收缩加强了残留的突触连接，并增强了 马达性能。然而，中到重度中风后PCMS的行为影响，特别是合并使用时 具有功能性的任务，都是未知的。因此，了解PCMS在卒中康复中的潜力的关键一步是- 胆化症是在功能性任务中使用PCMS，以增强更多受损个体的特定任务练习 中风后。因此，我们的中心假设是，在功能相关的自愿运动期间交付PCM (或任务特定的PCMS)将改善中至重度中风后的皮质脊髓传递和手功能。 为此，使用受试者内部重复测量设计，我们将在三个条件下(特定于任务)测试每个参与者 PCM、特定于任务的Sham-PCM和PCMS-REST)。拟议的概念证明研究将评估- 评估任务特异性PCMS对中、重度卒中患者的短期神经生理和行为影响。

ABSTRACT Among the 800,000 individuals who sustain a stroke annually in the United States, up to 65% continue to experience mod- erate-to-severe impairments in one hand six months or more, limiting their ability to perform daily tasks. These impairments, often characterized by the limited functional wrist and finger extension (< 20º), prevent the use of the paretic hand in func- tional tasks. Functional electrical stimulation (FES), commonly used to promote repeated use of the paretic hand in func- tional tasks, shows modest and transient effects in this population. Several non-invasive approaches of neuromodulation [e.g., repeated transcranial magnetic stimulation (rTMS), transcranial direct current stimulation, or paired associative stim- ulation] have also been applied to cortical motor areas, in either the same hemisphere as the stroke or contralaterally, to augment the effects of FES-facilitated task-specific practice. However, there is limited evidence supporting the effectiveness of these approaches. Thus, it is critical to examine alternative approaches to improving hand function and functional inde- pendence in this more impaired population. Our long-term goal is to develop mechanistic and theory-driven rehabili- tation interventions to improve hand function and functional independence in individuals with severe stroke. The strength of the synaptic connections between corticospinal axons and spinal motor neurons—which is severely affected after stroke—is essential to produce functionally relevant voluntary movements. Emerging evidence points to the potential for the reorganization of residual corticospinal inputs on spinal motor neuron pools to support recovery after stroke. Paired corticospinal-motor neuronal stimulation (PCMS) has been shown to strengthen the synapse between surviving corticospi- nal axons and spinal motor neurons. In PCMS, TMS is paired with peripheral nerve stimulation (PNS) such that the TMS- evoked corticospinal volleys arrive at corticospinal-motor neuronal synapses ~1-2 ms before the antidromic activation of spinal motor neurons via PNS. Previous research in individuals with incomplete spinal cord injury indicates that PCMS delivered during voluntary contraction elicits greater gains in corticospinal transmission (i.e., the size of motor evoked potentials [MEPs]) than at rest. These improvements in corticospinal transmission were also associated with improvements in hand function, indicating that voluntary contraction during PCMS strengthens residual synaptic connections and enhances motor performance. However, the behavioral effects of PCMS after moderate-to-severe stroke, particularly when combined with a functional task, are not known. Therefore, a critical step in understanding the potential of PCMS in stroke reha- bilitation is to employ PCMS during a functional task to augment task-specific practice in more impaired individuals after stroke. Thus, our central hypothesis is that delivering PCMS during functionally relevant voluntary movements (or task-specific PCMS) will improve corticospinal transmission and hand function after moderate-to-severe stroke. To this end, using a within-subjects repeated measures design, we will test each participant on three conditions (task-specific PCMS, task-specific sham-PCMS, and PCMS-rest) in a randomized order. The proposed proof of concept study will eval- uate the short-term neurophysiological and behavioral effects of task-specific PCMS after moderate-to-severe stroke.