The contribution of premotor cortex to recovery after stroke.

前运动皮层对中风后恢复的贡献。

• 批准号: 10720483
• 负责人: DAVID GUGGENMOS
• 金额: $ 44.92万
• 依托单位: UNIVERSITY OF KANSAS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-21 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10720483
• 关键词: Affect; Agonist; American; Anatomy; Animal Model; Animals; Area; Basic Science; Behavioral; Bilateral; Brain; Brain Injuries; Brain region; Chronic; Clinical; Continuous Infusion; Coupled; Distant; GABA-A Receptor; Goals; Health; Implant; Individual; Injury; Intervention; Left; Lesion; Location; Long-Term Care; Measurement; Measures; Mediating; Microelectrodes; Modeling; Motor; Motor Activity; Motor Cortex; Movement; Muscimol; Neuronal Plasticity; Neurons; Outcome; Performance; Persons; Physiological; Play; Population; Process; Public Health; Quality of life; Rattus; Recovery; Recovery of Function; Rehabilitation therapy; Research; Role; Science; Shapes; Speed; Spinal Cord; Stroke; Structure; Time; Tracer; Training; Translating; United States; behavioral outcome; critical period; disability; experience; functional disability; hemiparesis; improved; in vivo; injury recovery; innovation; ischemic injury; medical complication; motor control; motor disorder; motor function recovery; motor impairment; motor recovery; motor rehabilitation; muscle strength; neural; neural tract; neurite growth; novel; novel therapeutics; post stroke; pre-clinical; research study; response; skills; somatosensory

Project Summary/Abstract The goal of this project is to determine how ipsilesional premotor cortex facilitates recovery of motor function after ischemic injury in primary motor cortex. When an individual suffers damage to primary motor cortex, they often experience permanent reductions in motor function, including decreased motor coordination, muscle strength, movement speed and movement accuracy. While some spontaneous recovery can occur during the ensuing weeks to months, functional impairments often persist, leading to a reduction in quality of life and an increase in prolonged medical complications and expenses. Over the past two decades, basic research studies in pre-clinical animal models of brain injury, as well as clinical populations, have suggested that the brain can undergo structural and functional reorganization within and between spared regions. This neuroplasticity is thought to underpin functional recovery, however its manifestation as increases in task-related motor function has yet to be established. We have proposed that when primary motor cortex is damaged through ischemic injury, spared sensorimotor areas can take over some volitional control of motor function, and that the ipsilesional premotor cortex plays the biggest role in this control. In this project, we will investigate the timing and contribution of premotor cortex on both spontaneous motor recovery and recovery facilitated by rehabilitative intervention in a rat model of ischemic injury. First, we will establish the time period when premotor cortex contributions are necessary for spontaneous recovery to occur by temporarily inactivating premotor cortex after the ischemic injury (Aim 1). We will then determine if the task-related activity within premotor cortex is altered following the injury, whether these alterations impact the population level encoding of these tasks, the role rehabilitation has in shaping any novel task related activity and, if PM is inactivated, if task-related motor encoding occurs in other cortical areas (Aim 2). Finally, we will establish the relationship between the timing of premotor cortex reorganization and the strength of functional connectivity between spared areas using a stimulation-evoked cortical connectivity measurement and then determine if this physiological marker matches the novel anatomical sprouting from premotor cortex that occurs after an ischemic injury (Aim 3). This project is innovative as it uses a within-animal model to assess 1) how different cortical areas reorganize to restore motor function and 2) the impact of rehabilitation therapy on this reorganization. This project has a significant potential health impact, as the elucidation of location, timing and mechanisms related to functional behavioral recovery, especially when coupled to rehabilitative therapy, will create a complete picture of the neural substrates of recovery. This information is critical to maximize existing therapies and give rise to novel applications for the treatment of brain injuries.

项目摘要/摘要 该项目的目的是确定IPSILESICERIALS PRESOR CORTEX如何促进运动功能的恢复 原发性运动皮层的缺血性损伤后。当一个人损坏原发运动皮层时，他们 通常会体验到运动功能的永久降低，包括运动协调降低，肌肉 力量，运动速度和运动精度。虽然可能会在 随后的几周到几个月，功能障碍经常持续存在，导致生活质量的降低和 长期医疗并发症和费用的增加。在过去的二十年中，基础研究 在临床前动物模型中，脑损伤以及临床人群都表明大脑可以 在蓄能区域内和之间经历结构和功能重组。这种神经可塑性是 被认为是功能恢复的基础，但是随着任务相关的电机功能的增加而表现出来 尚未建立。我们提出，当一级运动皮层通过缺血受损时 受伤，宽敞的感觉运动区域可以接管运动功能的某些自愿控制，并且iPsilesionsions 前皮层在该控制中起着最大的作用。在这个项目中，我们将调查时间和贡献 恢复性干预措施促进的自发运动恢复和恢复的前后皮层 缺血性损伤的大鼠模型。首先，我们将确定前端皮质贡献的时间段 自发恢复所必需的，是通过缺血性损伤后暂时灭活前皮层而发生的 （目标1）。然后，我们将确定受伤后前皮层中与任务相关的活动是否改变， 这些改变是否影响这些任务的人口水平，康复的作用 塑造与任务相关的任何新型与任务相关的活动，如果PM被灭活，如果与任务相关的电机编码发生在其他 皮质区域（AIM 2）。最后，我们将建立前马皮的时间之间的关系 使用刺激诱发 皮质连通性测量，然后确定此生理标记是否与新的解剖学相匹配 从缺血性损伤后发生的前皮层发芽（AIM 3）。这个项目是创新的，因为它使用 一个可以评估的动物内模型1）不同的皮质区域如何重组以恢复运动功能； 2） 康复疗法对这种重组的影响。该项目具有重大的健康影响，因为 阐明与功能行为恢复有关的位置，时机和机制，尤其是在 结合康复疗法，将为恢复神经底物创建完整的图片。这 信息对于最大化现有疗法至关重要，并引起新的脑治疗应用 受伤。