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

• 批准号: 9914139
• 负责人: JULIUS P DEWALD
• 金额: $ 50.91万
• 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: 2019-05-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9914139
• 关键词: Affect; Biological Markers; Brachial Paresis; Brain; Brain Stem; Cell Nucleus; Chronic; Contralateral; Corticospinal Tracts; Coupling; Development; Diffusion Magnetic Resonance Imaging; Discrimination; Early Intervention; Elbow; Electroencephalography; Fingers; Functional Magnetic Resonance Imaging; Future; Generations; Goals; Hand; Hand functions; Hospitalization; Hour; Human; Impairment; Individual; Inpatients; Intervention; Isometric Exercise; Joints; Lesion; Lifting; Link; Measures; Mediator of activation protein; Morphology; Motor; Motor Cortex; Motor Pathways; Movement; Outcome; Paralysed; Participant; Pathway interactions; Patient Selection; Pattern; Population; Primates; Quality of life; ROC Curve; Recovery; Recovery of Function; Red nucleus structure; Rehabilitation therapy; Research; Residual state; Resolution; Resources; Rest; Reticular Formation; Severities; Shoulder; Signal Transduction; Specialist; Stroke; Structure; System; Testing; Time; Torque; Upper Extremity; Work; Wrist; arm; arm function; base; brain abnormalities; chronic stroke; density; disability; grasp; hand dysfunction; hemiparesis; hemiparetic stroke; improved; longitudinal analysis; motor control; motor impairment; motor recovery; neuromechanism; post stroke; predictive marker; relating to nervous system; robotic device; spinal tract; stroke recovery; stroke survivor; synergism

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 手臂和手部功能受损是中风患者慢性残疾的主要原因 幸存者。除了无力或瘫痪外，手臂/手也会受到异常屈曲协同作用的影响 – 当一个人试图举起手臂时，肘部、手腕和手指不自觉地弯曲。屈曲协同作用 损害了伸手和张开手的能力，并减少了功能期间对抓握力量的控制 任务，从而加剧中风幸存者的功能缺陷。目前大多数治疗都是轻度至中度 受损的人专注于扭转肘部/手部的无力，而不考虑近端关节，这可能 基于屈曲协同作用的逐步表达，对到达和抓握产生不利影响。 正常手臂/手功能所需的精细运动控制主要由对侧皮质脊髓驱动 道。皮质脊髓和皮质延髓（即离皮质）通路因中风受损后，会出现 对对侧皮质球脊髓束的依赖增加。根据灵长类动物研究，增加 对这些“低分辨率”系统的依赖导致与屈曲协同作用一致的关节耦合模式 人类中风后观察到的模式。随着时间的推移，预计对对侧运动皮质的依赖也会更大 导致对侧结构束完整性的逐渐增加，同时减少离皮质束 受损半球的完整性。因此，我们的中心假设是，缺血性损伤 离皮质束导致对对侧间接皮质球脊髓束的更大依赖，从而导致 增加对侧皮层和脑干核之间的功能连接并增强结构 球脊髓投影的形态可预测屈曲协同和恢复的表达 伸手和手的功能。为了检验这个假设，我们建议量化是否有更多的使用 对侧感觉运动皮层作为外展负荷和运动损伤严重程度的函数及其 对到达和抓握的影响（目标 1）。然后我们建议量化结构形态和功能 皮质脊髓和对侧皮质球脊髓投射与脑干运动核的连接 慢性中风参与者（目标 2）。最后，我们计划对关系进行纵向分析 对侧球脊髓投射的结构形态与运动恢复之间，具体而言， 评估早期形态变化作为慢性运动恢复结果的预测生物标志物（目标 3）。这 这是大脑功能和结构的首次纵向变化将与协同诱导的运动联系起来 中风患者上肢麻痹的损伤。这些结构和功能生物标志物 运动通路的变化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剩余皮质资源，从而很大程度上避免结构性损伤 以及间接对侧运动通路的功能改变，并最大限度地减少对运动的破坏性影响 屈曲协同作用。