The Loss of Independent Joint Control of the Upper Limb in Spastic Hemiparetic CP

项目摘要 小儿型偏瘫（PH）导致身体一侧的运动障碍， 超过三分之一的脑瘫病例，这是儿童时期最常见的运动障碍。电机 这一人群的障碍包括虚弱、运动协同作用和运动之间的耦合 四肢（手臂之间和瘫痪的手臂和腿之间），所有这些都限制了功能独立性 整个生命周期的流动性。至关重要的任务，如达到和把握，需要无数的日常 活动，包括参与课堂，变得有限或不可能。在上一个周期中， R 01，我们发现在神经发育过程中脑损伤的时间影响了 无力，肩外展与肘、腕和手指屈曲的不自主耦合（屈曲协同）， 和上肢之间的无意识耦合。我们之前的工作揭示了 损伤时间对神经结构保存的重要性，以神经结构的完整性表示。 白色物质，因为它们可能会受到不同的影响时，神经发育阶段的伤害 发生。在早期损伤（产前），可能有直接的同侧皮质脊髓 作为典型神经发育的一部分而存在的投射。我们假设这解释了 减少了上肢之间的屈曲协同作用和更大的运动耦合。相反地， 在以后的损伤中（围产期和产后），我们假设这些同侧的发育修剪 皮质脊髓投射正在进行中（围产期）或已经发生（产后），导致增加 依赖间接的同侧皮质网状脊髓通路来控制麻痹肢体的运动。这些 间接路径分支在脊髓显著，解释了屈曲协同作用的存在， 麻痹腿和手臂之间的不正常的不自主耦合。为了确定时间的影响， PH患者在功能性伸手-抓握任务中运动损伤的损伤和肢体负荷以及与 神经微结构形态，我们建议：1）量化上肢达到的距离和手 开/关能力; 2）确定肢体间运动耦合的表达; 3）识别 同侧和对侧大脑半球运动通路的白色和灰质复杂性变化 以及脑干。因此，拟议的研究将首次调查时间的影响， 脑损伤对儿童期偏瘫患者运动通路复杂性的影响 和肢体间耦合功能障碍。这将为更有效地开发 用于治疗肢体内和肢体间异常耦合的针对性、损伤时间特异性干预措施 来改善这一人群的功能。

PROJECT SUMMARY Pediatric-onset hemiplegia (PH) causes movement impairments on one side of the body and accounts for more than a third of all cases of cerebral palsy, the most common motor disability in childhood. Motor impairments in this population include weakness, movement synergies, and coupling movements between limbs (between arms and between paretic arm and legs), all of which limit independence with functional mobility throughout the lifespan. Crucial tasks, such as reaching and grasping, required for countless daily activities including participating in the classroom, become limited or impossible. In the previous cycle of this R01, we discovered that the timing of brain injury during neurodevelopment impacted the expression of weakness, involuntary coupling of shoulder abduction with elbow, wrist, and finger flexion (flexion synergy), and involuntary coupling between upper limbs during isometric tasks. Our previous work uncovered the importance of the timing of the injury on the preservation of neural structures, expressed in the integrity of white matter, as they may be affected differently based on the stage of neurodevelopment when the injury occurs. During early injuries (PRE-natal), there may be preservation of direct ipsilateral corticospinal projections that are present as part of typical neural development. We hypothesize that this explains the reduced presence of the flexion synergy and the greater movement coupling between upper limbs. Conversely, in later injuries (PERI- and POST-natal) we hypothesize that the developmental pruning of these ipsilateral corticospinal projections is in process (PERI-natal) or has already occurred (POST-natal) leading to increased reliance in indirect ipsilateral corticoreticulospinal pathways to control movement of the paretic limbs. These indirect pathways branch significantly at the spinal cord, explaining the presence of the flexion synergy and abnormal involuntary coupling between the paretic leg and arm. In an effort to determine the effects of time of injury and limb loading on motor impairments during functional reaching-grasping tasks in PH and the link to neural microstructural morphology, we propose to: 1) quantify upper extremity reaching distance and hand opening/closing ability; 2) determine the expression of between-limb movement coupling; and 3) identify the changes in white and gray matter complexity of motor pathways in ipsilesional and contralesional hemispheres as well as the brainstem. As such, the proposed research will, for the first time, investigate the effect of time of brain injury on motor pathway complexity in individuals with pediatric-onset hemiplegic who express within-limb and between-limb coupling dysfunction. This will provide the foundation for the development of more effective targeted, time-of-injury specific interventions for the treatment of abnormal within- and between-limb coupling to improve functional capabilities in this population.