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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

基本信息

批准号：
9978864
负责人：
JULIUS P DEWALD
金额：
$ 22.76万
依托单位：
NORTHWESTERN UNIVERSITY AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-07-16 至 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9978864
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

项目摘要

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。中风后的运动障碍，如上肢屈曲协同和异常的伸展反射，极大地影响一个人执行日常生活活动的能力。尽管各种不同的中风后运动恢复的临床干预、康复治疗，尤其是对更多受损的患者对个人来说，只是最低限度的有效。这是由于：1)我们对具体问题的理解仍然存在许多差距中风后运动障碍的潜在机制，为临床实践提供信息；2)缺乏敏感度用于确定中风引起的神经通路中断所致神经可塑性的生物标记物在康复期间。我们的长期目标是开发一种灵敏的方法来定量评估由卒中后剩余运动通路的利用，这将使更好地检查卒中恢复和康复干预措施的评价。我们先前的研究表明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所致，在中风引起的同侧皮质脊髓投射丧失后。因此，这项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效应表达的联系和异常伸展反射，通过检查运动通路的神经连接性的变化作为肩部外展(SABD)负荷。与直接的皮质脊髓束不同，这些间接通路包括更多的突触，从而可能导致通过运动通路增强的非线性神经连接与突触行为的非线性S形及其跨突触的累积效应有关。因此，我们的中央假设是：1)在抬起瘫痪的手臂时，间接运动通路的使用增加，需要 SABD和导致屈曲协同作用，将导致增强大脑和肌肉之间的非线性连接 2)间接运动通路的募集也会影响伸展反射，特别是其经皮质反射组件，导致伸展扰动和肌肉活动。最后，这些间接通路可能延长经皮质的神经传递延迟。反射环，导致扰动和肌肉活动之间的时间滞后增加。使用我们最近的发展的非线性连通性方法和机械控制的实验范式，我们的目标是通过以下方法验证这些假设：1)比较大脑和肌肉活动之间的线性和非线性连接脑卒中偏瘫患者不同水平SABD扭矩的产生；2)量化变化作为SABD扭矩水平的函数的中风后伸展反射的非线性连接性和时间延迟。AS 这样，这个项目将提供新的敏感的生物标志物来确定间接运动通路的招募导致偏瘫后上肢功能障碍。这也将带来更好的对卒中所致运动障碍潜在神经机制的理解有助于临床实践以对抗单侧脑损伤后的屈曲协同和相关的过度活跃的伸展反射。