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。中风后运动障碍，如上肢屈曲协同和异常伸展反射， 严重影响个人的日常生活能力。尽管发展了各种 中风后运动恢复的临床干预，康复治疗，特别是在更受损的 个人，只有最低限度的有效性。这是由于：1）我们对具体问题的理解仍然存在许多差距。 脑卒中后运动障碍的潜在机制，告知临床实践，和2）缺乏敏感的 生物标志物，以确定由中风引起的神经通路中断引起的神经可塑性 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 利用中风后剩余的运动通路，这将允许更好地检查中风恢复， 评估康复干预措施。我们之前的研究表明，轻偏瘫后的运动障碍 中风很可能是由于对通过脑干的对侧间接运动通路的依赖增加， 在中风引起的同侧皮质脊髓投射丧失之后。因此，本提案的目的是 定量确定间接运动通路的使用及其与屈曲协同作用表达的联系 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一个功能， 肩外展（SABD）载荷。与直接皮质脊髓束相反，这些间接通路包含 更多的突触，这因此可能导致通过运动通路的增强的非线性神经连接， 突触行为的非线性S形形状及其在突触之间的累积效应。因此，我们的中央 假设是：1）在举起麻痹手臂时，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 经皮质反射成分，导致拉伸扰动和 肌肉活动最后，这些间接通路可能延长经皮层的神经传递延迟 反射回路，导致扰动和肌肉活动之间的时间延迟增加。利用我们最近 开发的非线性连接方法和机械良好控制的实验范例，我们的目标是 测试这些假设：1）比较大脑和肌肉活动之间的线性与非线性连接， 在轻偏瘫中风后个体中产生不同水平的SABD扭矩; 2）量化变化 非线性连接和时间延迟的牵张反射中风后作为一个函数的SABD扭矩水平。作为 因此，该项目将提供新的敏感生物标志物，确定间接运动通路的募集 导致偏瘫性中风后上肢功能残疾。这也将导致更好的 了解脑卒中引起的运动损伤的神经机制，为临床实践提供信息 以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。