Determination of the Recruitment of Indirect Motor Pathways in Chronic Hemiparetic Stroke

慢性偏瘫中风间接运动通路募集的测定

• 批准号: 9809617
• 负责人: JULIUS P DEWALD
• 金额: $ 18.85万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-16 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9809617
• 关键词: Activities of Daily Living; Affect; Behavior; Biological Markers; Brain; Brain Injuries; Brain Stem; Chronic; Clinical; Contralateral; Corticospinal Tracts; Coupling; Development; Distant; Elbow; Elbow joint structure; Electroencephalography; Evaluation; Extensor; Fingers; Flexor; Frequencies; Future; Generations; Goals; Hand; Hand functions; Handedness; Hyperactive behavior; Impairment; Individual; Interruption; Intervention; Joints; Knowledge; Lead; Lesion; Lifting; Link; Measures; Mechanics; Methods; Motor; Motor Cortex; Motor Pathways; Movement; Muscle; Neural Pathways; Neuronal Plasticity; Neurons; Oligonucleotides; Paresis; Participant; Pathway interactions; Positioning Attribute; Recovery; Reflex action; Rehabilitation therapy; Reporting; Research; Research Personnel; Shapes; Shoulder; Sigmoid colon; Signal Transduction; Stretching; Stroke; Synapses; Synaptic Transmission; System; Testing; Time; Torque; Upper Extremity; Weight Lifting; Wrist; abnormal reflex; arm; arm function; arm paresis; base; clinical practice; combat; functional disability; hemiparetic stroke; improved; indexing; innovation; models and simulation; motor impairment; motor recovery; neural model; neuromechanism; novel; novel therapeutic intervention; post stroke; recruit; relating to nervous system; spasticity; stretch reflex; stroke recovery; stroke rehabilitation; synergism

Abstract. Motor impairments post-stroke, such as the upper limb flexion synergy and abnormal stretch reflexes, greatly affect an individual’s ability to implement activities of daily living. Despite the development of various clinical interventions for motor recovery after stroke, rehabilitation treatments, especially in more impaired individuals, are only minimally effective. This is due to: 1) many remaining gaps in our understanding of specific mechanisms underlying motor impairments post stroke that inform clinical practice, and 2) lack of sensitive biomarkers to determine the neuroplasticity resulting from interruptions of neural pathways caused by the stroke and during recovery. Our long-term goal is to develop a sensitive way to quantitatively assess the lesion-induced utilization of remaining motor pathways post stroke, which would allow better examination of stroke recovery and evaluation of rehabilitation interventions. Our previous studies indicate that motor impairments post hemiparetic stroke are likely caused by an increased reliance on contralesional indirect motor pathways via the brainstem, following stroke-induced losses of ipsilesional corticospinal projections. Thus, the objective of this proposal is to quantitatively determine the usage of indirect motor pathways and its link to the expression of the flexion synergy and abnormal stretch reflexes, by examining changes in neural connectivity of motor pathways as a function of shoulder abduction (SABD) load. In contrast to the direct corticospinal tract, these indirect pathways contain more synapses, which thus may cause an enhanced nonlinear neural connectivity via the motor pathways due to the nonlinear sigmoid shape of synaptic behavior and its cumulative effect across synapses. Thus, our central hypotheses are that: 1) an increased usage of indirect motor pathways while lifting the paretic arm, requiring SABD and causing the flexion synergy, will lead to enhanced nonlinear connectivity between brain and muscle activity; 2) the recruitment of indirect motor pathways will also affect the stretch reflex, in particular, its transcortical reflex component, resulting in increased nonlinear connectivity between stretch perturbations and muscle activity. Finally, these indirect pathways may prolong the neural transmission delay in the transcortical reflex loop, resulting in an increased time lag between perturbations and muscle activity. Using our recently developed nonlinear connectivity method and mechanically well-controlled experimental paradigms, we aim to test these hypotheses by: 1) comparing linear vs. nonlinear connectivity between brain and muscle activity during the generation of different levels of SABD torque in individuals post hemiparetic stroke; 2) quantifying changes of nonlinear connectivity and time delay of the stretch reflex post-stroke as a function of SABD torque level. As such, this project will provide new sensitive biomarkers that determine the recruitment of indirect motor pathways resulting in functional disability of upper extremity post hemiparetic stroke. This will also lead to a better understanding of neural mechanisms underlying stroke-induced motor impairments that inform clinical practice to combat the flexion synergy and associated hyperactive stretch reflexes following a unilateral brain injury.

抽象的。中风后运动障碍，例如上肢屈曲协同作用和异常拉伸反射， 极大地影响个人实施日常生活活动的能力。尽管发展了各种 中风后，康复治疗后的运动恢复临床干预措施，尤其是在更受损的情况下 个人，只有最小的有效。这是由于：1）我们对特定的理解中剩下的差距 中风后的机制为临床实践提供了障碍，2）缺乏敏感的 生物标志物确定由中风引起的神经病变中断引起的神经塑性 并在恢复期间。我们的长期目标是开发一种敏感的方法来定量评估病变引起的 中风后剩余的电路途径的利用，这将可以更好地检查中风恢复和 评估康复干预措施。我们先前的研究表明，偏瘫后运动障碍 中风可能是由于通过脑干对混凝土间接运动通路的依赖而引起的， 随着中风引起的ipsiles性皮质脊髓项目的损失。那是该提议的目的是 定量确定间接电动途径的使用及其与屈曲协同作用的链接 和通过检查电动路径的神经连通性的变化，与伸展反射异常 肩部绑架（SABD）负载。与直接皮质脊髓道相反，这些间接途径包含 更多的突触，因此可能会通过到期的电路通路引起增强的非线性神经连通性 突触行为的非线性乙状结肠形状及其跨突触的累积作用。那，我们的中心 假设是：1）在举起外侧臂时增加间接电路通路的使用情况增加 SABD并引起屈曲协同作用，将导致大脑和肌肉之间的非线性连通性增强 活动; 2）间接运动途径的募集也将影响拉伸反射，特别是 跨皮层反射成分，导致拉伸扰动和 肌肉活动。最后，这些间接途径可能会延长跨皮质的神经传递延迟 反射循环，导致扰动和肌肉活动之间的时间滞后。使用我们最近 开发的非线性连通方法和机械控制良好的实验范式，我们的目标是 通过：1）比较这些假设：1）比较在大脑和肌肉活动之间的线性与非线性连通性 偏瘫中风后个体中不同水平的SABD扭矩产生； 2）量化更改 拉伸后冲程后的非线性连通性和时间延迟与SABD扭矩水平的函数。作为 这样的项目将提供新的敏感生物标志物，以确定间接电路的募集 导致上肢中风后上肢的功能残疾。这也将导致更好 了解中风引起的运动障碍的神经机制，这些障碍为临床实践提供了信息 打击单侧脑损伤后的屈曲协同作用和相关的多动性拉伸反射。