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Contralesional Corticobulbospinal Structural and Functional Changes Post Stroke: Biomarkers for the upper limb flexion synergy

中风后对侧皮质球脊髓结构和功能变化：上肢屈曲协同作用的生物标志物

基本信息

批准号：
10832173
负责人：
JULIUS P DEWALD
金额：
$ 8.28万
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：
2019-05-01 至 2025-04-30
项目状态：
未结题

项目摘要

Project Summary Impaired arm and hand function is a major cause of chronic disability among stroke survivors. In addition to weakness or paralysis, the arm/hand is also affected by the abnormal flexion synergy – involuntary elbow, wrist, and finger flexion when an individual attempts to lift the arm. The flexion synergy compromises the ability to reach and open the hand and reduces the control of grasp strength during functional tasks, thus compounding the stroke survivor’s functional deficits. Most current treatments in mild to moderately impaired individuals focus on reversing weakness at the elbow/hand without regard to proximal joints which can have a detrimental effect on reaching and grasping based on the progressive expression of the flexion synergy. The fine motor control required for normal arm/hand function is largely driven by the contralateral corticospinal tract. After corticospinal and corticobulbar (i.e., corticofugal) pathways are damaged by a stroke, there is increased reliance on contralesional cortico-bulbo-spinal tracts. Based on primate research, an increased reliance on these “lower-resolution” systems causes joint coupling patterns consistent with the flexion synergy pattern seen in humans post-stroke. Greater reliance on contralesional motor cortices over time is also expected to result in progressive increases in structural tract integrity in the contralesional- while reducing corticofugal tract integrity in the lesioned- hemisphere. Our central hypothesis therefore is that ischemic damage to the corticofugal tracts causes a greater reliance on contralesional indirect corticobulbospinal tract resulting in increased functional connectivity between contralesional cortex and brainstem nuclei and enhanced structural morphology of bulbospinal projections that are predictive of the expression of the flexion synergy and recovery of reaching and hand function. To test this hypothesis, we propose to quantify whether there is greater use of contralesional sensorimotor cortices as a function of abduction loading and motor impairment severity and its impact on reaching and grasping (Aim 1). We then propose to quantify the structural morphology and functional connectivity of corticospinal and contralesional corticobulbospinal projections to motor nuclei in the brain stem in chronic stroke participants (Aim 2). Lastly, we plan to conduct a longitudinal analysis of the relationship between structural morphology of contralesional bulbospinal projections and motor recovery, and specifically, evaluate early morphological change as a predictive biomarker for chronic motor recovery outcome (Aim 3). This is the first-time longitudinal change in brain function and structure will be linked to synergy induced motor impairments in the paretic upper limb of individuals with stroke. These structural and functional biomarkers of motor pathways changes will guide the timely application of anti-synergy interventions that will promote the maximal utilization of spared corticofugal resources in the lesioned hemisphere thus largely avoiding structural and functional changes to indirect contralesional motor pathways and minimizing the devastating effects of the flexion synergy.

项目摘要手臂和手功能受损是中风患者慢性残疾的主要原因幸存者。除了虚弱或瘫痪外，手臂/手还受到异常屈曲协同的影响-- 当个人试图抬起手臂时，不自觉地屈肘、屈腕和屈指。屈曲协同效应影响了伸手和张开手的能力，并减少了在功能训练中对握力的控制任务，因此加重了中风幸存者的功能缺陷。目前大多数治疗方法为轻度至中度受损者专注于扭转肘部/手部的无力，而不考虑近端关节，这可能在屈曲协同的渐进式表达的基础上，对伸展和握力产生不利影响。正常手臂/手功能所需的精细运动控制很大程度上是由对侧皮质脊髓驱动的一条小路。在中风损害皮质脊髓和皮质球(即皮质疏松)通路后，存在更多地依赖对侧皮质-延髓-脊髓束。基于灵长类动物的研究，增加了对这些“低分辨率”系统的依赖导致关节耦合模式与屈曲协同作用一致。在人类中风后出现的模式。随着时间的推移，预计还会更多地依赖对侧运动皮质在对侧导致结构束完整性的进行性增加，同时减少皮质疏松束受损大脑半球的完整性。因此，我们的中心假设是脑缺血损伤皮质分离肌束导致更多地依赖对侧间接皮质脊髓束，导致对侧皮质和脑干核团之间的功能连接增强和结构增强预测屈曲、协同和恢复表达的球脊髓投射的形态伸手和手的功能。为了检验这一假设，我们建议量化是否有更多的使用对侧感觉运动皮质与外展负荷和运动损伤严重程度的关系对伸手和抓住的影响(目标1)。然后我们建议对结构形态和功能进行量化皮质脊髓和对侧皮质球脊髓投射与脑干运动核团的联系在慢性中风参与者中(目标2)。最后，我们计划对这一关系进行纵向分析对侧球脊髓投射的结构形态与运动恢复之间的关系，特别是，评估早期形态改变作为预测慢性运动恢复结果的生物标志物(目标3)。这首次出现的大脑功能和结构的纵向变化是否会与协同作用有关，诱发运动中风患者偏瘫上肢的损害。这些结构和功能上的生物标志物运动通路的改变将指导及时应用反协同干预措施，从而促进最大限度地利用受损半球的备用皮质分离资源，从而在很大程度上避免了结构性和间接收缩运动通路的功能变化，并将屈曲协同作用。

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Reply from Jacob Graves McPherson, Albert Chen, Michael D. Ellis, Jun Yao, C. J. Heckman and Julius P. A. Dewald.

Jacob Graves McPherson、Albert Chen、Michael D. Ellis、Jun Yao、C. J. Heckman 和 Julius P. A. Dewald 的回复。

DOI：
10.1113/jp278464
发表时间：
2019
期刊：
The Journal of physiology
影响因子：
0
作者：
McPherson,JacobGraves;Chen,Albert;Ellis,MichaelD;Yao,Jun;Heckman,CJ;Dewald,JuliusPA
通讯作者：
Dewald,JuliusPA

A geometric approach to quantifying the neuromodulatory effects of persistent inward currents on individual motor unit discharge patterns.