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.

项目概要/摘要 该项目的目标是确定同病前运动皮层如何促进运动功能的恢复 初级运动皮层缺血性损伤后。当一个人的初级运动皮层受到损害时，他们 经常会出现运动功能永久性下降，包括运动协调性下降、肌肉 力量、动作速度和动作精度。虽然在此期间可能会发生一些自发恢复 在接下来的几周到几个月内，功能障碍往往持续存在，导致生活质量下降和 长期医疗并发症和费用增加。近二十年来，基础研究 在脑损伤的临床前动物模型以及临床人群中，表明大脑可以 在受灾地区内部和之间进行结构和功能重组。这种神经可塑性是 被认为支持功能恢复，但其表现为任务相关运动功能的增加 尚未确定。我们提出，当初级运动皮层因缺血而受损时 受伤后，幸存的感觉运动区域可以接管一些运动功能的意志控制，并且同损伤的感觉运动区域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发挥着最大的作用。在这个项目中，我们将调查时间安排和贡献 运动前皮层对自发运动恢复和康复干预促进的恢复的影响 大鼠缺血性损伤模型。首先，我们将确定前运动皮层贡献的时间段 缺血性损伤后，通过暂时失活前运动皮层来实现自发恢复所必需的 （目标 1）。然后我们将确定前运动皮层内与任务相关的活动在受伤后是否发生改变， 这些改变是否会影响这些任务的人口水平编码，康复在其中的作用 塑造任何新的任务相关活动，如果 PM 失活，如果任务相关的运动编码发生在其他 皮质区域（目标 2）。最后，我们将建立前运动皮层时序之间的关系 使用刺激诱发的重组和备用区域之间的功能连接强度 皮质连接测量，然后确定该生理标记是否与新的解剖结构相匹配 从缺血性损伤后发生的运动前皮层发芽（目标 3）。该项目具有创新性，因为它使用了 动物内模型用于评估 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 与康复治疗相结合，将创建康复神经基础的完整图景。这 信息对于最大化现有疗法并产生脑部治疗的新应用至关重要 受伤。