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

加强中重度慢性中风后瘫痪手部肌肉的任务特异性激活

• 批准号: 10591661
• 负责人: Amit Sethi
• 金额: $ 23.31万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-02-01 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10591661
• 关键词: Affect; Area; Axon; Behavioral; Biomechanics; Brain; Chronic; Clinical; Clinical Trials; Contralateral; Data; Effectiveness; Evidence based intervention; Exclusion; Extensor; Fingers; Foundations; Funding; Future; Goals; Hand; Hand functions; Impairment; Individual; Intervention; Knowledge; Long-Term Effects; Long-Term Potentiation; Measures; Motor; Motor Cortex; Motor Evoked Potentials; Motor Neurons; Movement; Muscle; Nerve; Outcome; Paralysed; Paresis; Participant; Patients; Performance; Peripheral Nerve Stimulation; Population; Production; Randomized; Recovery Support; Rehabilitation therapy; Research; Residual state; Rest; Spinal; Spinal cord injury; Stroke; Synapses; Testing; Training; Transcranial magnetic stimulation; United States; Upper Extremity; Vertebral column; Wrist; chronic stroke; cohort; design; effective intervention; effective therapy; experience; extensor digitorum; functional electrical stimulation; functional independence; grasp; hand rehabilitation; improved; innovation; kinematics; motor recovery; neurophysiology; neuroregulation; novel; post stroke; prevent; stroke rehabilitation; stroke survivor; theories; transcranial direct current stimulation; transmission process

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.

抽象的 在每年在美国维持中风的80万个人中，多达65％的人继续经历模式 一方面，六个月或更长时间的重度障碍，限制了他们执行日常任务的能力。这些障碍， 通常以有限的功能手腕和手指伸展为特征（<20º），以防止在func- 任务。功能电气模拟（FES），通常用于促进副手在func-中反复使用 统治任务，显示该人群中的适度和短暂影响。神经调节的几种非侵入性方法 [ [ulation]也已应用于皮质运动区域，在与中风或对侧相同的半球中 增强针对特定任务的FES效果。但是，有限的证据支持有效性 这些方法。这是至关重要的 在这个更受损的人群中的缘故。我们的长期目标是开发机械和理论驱动的康复 促进严重中风的个体的手部功能和功能独立性的干预措施。这 皮质脊髓轴突和脊柱运动神经元之间突触连接的强度 - 受到严重影响 中风后 - 对于产生功能相关的自愿运动至关重要。新兴证据指出了潜力 为了重组脊柱运动神经元池上残留的皮质脊髓输入，以支持中风后的恢复。配对 皮质脊髓运动神经元刺激（PCMS）已显示可增强生存性皮质孔之间的突触 NAL轴突和脊柱运动神经元。在PCM中，TMS与周围神经刺激（PN）配对，使得TMS- 诱发的皮质脊髓伏圈到达皮质脊髓运动神经元突触〜1-2 ms，触及激活前〜1-2 ms 脊柱运动神经元通过PNS。对脊髓损伤不完全的人的先前研究表明PCM 在自愿收缩期间递送会引起皮质脊髓传播的增长（即，电动机的尺寸诱发 潜力[MEP]）而不是休息。皮质脊髓传播的这些改进也与改进有关 在手功能中，表明PCMS强度在PCMS强度的残留突触连接并增强 运动性能。但是，中度中风后PCM的行为效应，尤其是当组合时 具有功能性任务，尚不清楚。因此，了解PCM在中风中的潜力的关键步骤 双向词是在功能性任务期间员工PCM，以增加更受损的人的特定任务实践 中风后。这是我们的中心假设是在功能相关的自愿运动中传递PCM （或特定于任务的PCM）将在中度到重度冲程后改善皮质脊髓传播和手部功能。 为此，使用受试者内重复测量设计，我们将测试每个参与三个条件的参与（特定于任务 PCM，特定于任务的SHAM-PCM和PCMS-REST）以随机顺序为单位。拟议的概念证明将评估 中度到重度中风后，任务特异性PCM的短期神经生理和行为影响。