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牵张反射， 极大地影响个人进行日常生活活动的能力。尽管发展了各种 中风后运动恢复的临床干预、康复治疗，尤其是受损程度较高的患者 个人而言，只能起到最低限度的作用。这是由于：1）我们对具体的理解还存在许多差距。 中风后运动障碍的潜在机制可为临床实践提供信息，2）缺乏敏感性 用于确定中风引起的神经通路中断导致的神经可塑性的生物标志物 以及恢复期间。我们的长期目标是开发一种灵敏的方法来定量评估损伤引起的 利用中风后剩余的运动通路，这将有助于更好地检查中风恢复和 评估康复干预措施。我们之前的研究表明偏瘫后运动障碍 中风可能是由于对通过脑干的对侧间接运动通路的依赖增加引起的， 中风引起的同病灶皮质脊髓投射丧失后。因此，本提案的目标是 定量确定间接运动通路的使用及其与屈曲协同表达的联系 和异常的牵张反射，通过检查运动通路的神经连接的变化作为函数 肩外展（SABD）负荷。与直接皮质脊髓束相比，这些间接途径包含 更多的突触，因此可能会通过运动通路增强非线性神经连接 突触行为的非线性 S 形及其跨突触的累积效应。因此，我们的中央 假设是：1）抬起瘫痪手臂时间接运动通路的使用增加，需要 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接增强 活动; 2）间接运动通路的募集也会影响牵张反射，特别是其 经皮层反射成分，导致拉伸扰动和 肌肉活动。最后，这些间接途径可能会延长经皮层的神经传递延迟。 反射环路，导致扰动和肌肉活动之间的时间滞后增加。使用我们最近 开发了非线性连接方法和机械良好控制的实验范式，我们的目标是 通过以下方式检验这些假设：1）比较大脑和肌肉活动之间的线性连接与非线性连接 偏瘫中风后个体产生不同水平的 SABD 扭矩； 2）量化变化 中风后牵张反射的非线性连接和时间延迟作为 SABD 扭矩水平的函数。作为 因此，该项目将提供新的敏感生物标志物来确定间接运动通路的募集 导致中风偏瘫后上肢功能障碍。这也将带来更好的 了解中风引起的运动障碍的神经机制，为临床实践提供信息 对抗单侧脑损伤后的屈曲协同作用和相关的过度活跃的牵张反射。