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.

项目总结/摘要 这个项目的目标是确定同侧运动前皮层如何促进运动功能的恢复 在初级运动皮层缺血性损伤后。当一个人的初级运动皮层受损时， 经常经历运动功能的永久性降低，包括运动协调性降低、肌肉萎缩、 力量、移动速度和移动准确性。虽然在治疗期间可能会发生一些自发恢复， 在随后的几周到几个月内，功能障碍往往持续存在，导致生活质量下降， 长期医疗并发症和费用增加。在过去的二十年里，基础研究 在脑损伤的临床前动物模型以及临床人群中，已经表明大脑可以 在未受影响的区域内和区域之间进行结构和功能重组。这种神经可塑性是 被认为是功能恢复的基础，但其表现为与任务相关的运动功能的增加 还有待确定。我们已经提出，当初级运动皮层通过缺血性损伤时， 受伤后，备用感觉运动区可以接管运动功能的一些意志控制， 前运动皮层在这种控制中起着最大的作用。在这个项目中，我们将调查的时间和贡献 运动前皮质对自发运动恢复和康复干预促进的恢复的影响 缺血性损伤的大鼠模型。首先，我们将建立运动前皮层贡献的时间段， 缺血性损伤后，运动前皮质暂时失活是自发恢复所必需的 (Aim 1）。然后，我们将确定运动前区皮层内与任务相关的活动是否在受伤后发生了改变， 无论这些变化是否影响这些任务的人口水平编码，康复在 塑造任何新的任务相关的活动，如果PM是失活的，如果任务相关的运动编码发生在其他 皮质区（Aim 2）。最后，我们将建立运动前区皮层的时间关系， 重组和强度之间的功能连接备用区使用刺激诱发的 皮质连接测量，然后确定该生理标记是否匹配新的解剖结构 从缺血性损伤后发生的前运动皮层发芽（目的3）。这个项目是创新的，因为它使用 动物体内模型，以评估1）不同的皮质区域如何重组以恢复运动功能，以及2） 康复治疗对这种重组的影响。该项目具有重大的潜在健康影响，因为 阐明与功能性行为恢复相关的位置、时间和机制，特别是当 再加上康复治疗，将创造一个完整的图片的神经基板的恢复。这 信息对于最大限度地利用现有疗法和产生治疗脑疾病的新应用至关重要。 受伤