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: 10378022
• 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/10378022
• 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.

手臂和手部功能受损是中风慢性残疾的主要原因