Neural dynamics of somatosensory guidance of dexterous movement in intact and stroke-injured networks

完整和中风损伤网络中灵巧运动体感引导的神经动力学

• 批准号: 10494237
• 负责人: Preeya Khanna
• 金额: $ 11.11万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-29 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10494237
• 关键词: Activities of Daily Living; Acute; Address; Anatomy; Animal Model; Animals; Area; Automobile Driving; Award; BRAIN initiative; Behavior; Behavioral; Body mass index; Brain; Cessation of life; Clinical; Clinical Research; Complex; Contralateral; Data; Data Analyses; Development; Electrophysiology (science); Evolution; Faculty; Feedback; Foundations; Freedom; Future; Hand; Hand functions; Human; Impairment; Institution; Intervention; Learning; Link; Location; Mathematics; Mentors; Methods; Modeling; Monitor; Motor; Motor Activity; Motor Cortex; Motor Pathways; Movement; Pathway interactions; Performance; Phase; Physical therapy; Population; Positioning Attribute; Primates; Process; Recording of previous events; Recovery; Robot; Role; Sensory; Sensory Receptors; Signal Transduction; Somatosensory Cortex; Stereotyping; Stroke; Survivors; Tactile; Thalamic structure; Training; United States; Ventral Posterolateral Nucleus; base; brain machine interface; combat; density; dexterity; disability; experimental study; grasp; hand dysfunction; hand rehabilitation; haptic interface; haptics; improved; injured; kinematics; neuroregulation; nonhuman primate; novel; novel therapeutics; post stroke; pre-clinical research; relating to nervous system; sensor; sensorimotor system; sensory cortex; sensory input; skill acquisition; skills; somatosensory; stereotypy; stroke recovery; stroke rehabilitation; stroke survivor; targeted treatment; theories; tool; virtual

PROJECT SUMMARY Stroke-causing illness, disability, and early death is set to double worldwide within the next 15 years. Despite physical therapy, about 50% of stroke survivors have impaired hand function, which strongly impacts activities of daily living and independence; novel treatment methods are urgently required. While most pre-clinical research addressing stroke recovery and rehabilitation focuses on restoring damaged descending movement pathways, dexterous hand function is also reliant on the brain receiving ascending somatosensory input and being able to use it to guide movements. Clinically and in animal models, deficits in somatosensory cortices predict worse recovery of hand function following stroke, though the functional mechanisms by which somatosensory signals support hand function remain poorly characterized. In this proposal, we aim to uncover how somatosensory signals drive motor activity during the acquisition and performance of dexterous manipulation behaviors in intact and post-stroke non-human primates. The main experimental approach of this proposal includes simultaneous high-density, high channel-count acute electrophysiological recordings from the somatosensory thalamus, primary somatosensory cortex, and primary motor cortex in intact and post-stroke non-human primates performing complex manipulation tasks. The main analytical approach includes modeling motor activity evolution as a combination of intrinsic motor cortical dynamics and inputs from somatosensory thalamic and somatosensory cortex. The hypothesis of this proposal is that somatosensory input signals guide the identification of effective motor activity trajectories that become frequently used and less input-dependent with improved manipulation skill. Thus, somatosensory signals are critical for improvement of manipulation skill and recovery of dexterity post-stroke. Completion of this proposal will identify nodes and functional interactions within the sensorimotor system that could be targeted with novel therapies for improving recovery of hand function following stroke. I will complete these aims with the guidance of an exceptional mentoring team led by Dr. Karunesh Ganguly and including Dr. Joni Wallis, Dr. Robert Morecraft, and Dr. Aaron Suminski. During the mentored phase of the award at UCSF, I will develop a state-of-the-art high channel-count, multi-area electrophysiological approach for monitoring the sensorimotor network. I will also conduct the proposed experiments in animals performing object manipulation tasks, pilot a haptic brain-machine-interface task, and focus on professional development in order to facilitate a successful transition into an independent faculty position at an academic institution.

项目概要 未来 15 年内，全球范围内由中风引起的疾病、残疾和过早死亡人数将增加一倍。尽管 物理治疗，约 50% 的中风幸存者手部功能受损，这严重影响活动 日常生活和独立性；迫切需要新的治疗方法。虽然大多数临床前研究 解决中风恢复和康复的重点是恢复受损的下行运动路径， 灵巧的手功能还依赖于大脑接收上升的体感输入并能够 用它来指导动作。在临床和动物模型中，体感皮层的缺陷预示着情况会更糟 中风后手部功能的恢复，通过体感信号的功能机制 支持手功能的特征仍然很差。在这个提案中，我们的目标是揭示体感如何 在完整地获得和执行灵巧操作行为期间，信号驱动运动活动 和中风后的非人类灵长类动物。 该提案的主要实验方法包括同时高密度、高通道数 来自体感丘脑、初级体感皮层的急性电生理记录 完整的和中风后的非人类灵长类动物的初级运动皮层执行复杂的操作任务。这 主要分析方法包括将运动活动进化建模为内在运动皮质的组合 来自体感丘脑和体感皮层的动力学和输入。本提案的假设 体感输入信号指导识别有效的运动活动轨迹，从而成为 经常使用，较少依赖输入，并提高操作技能。因此，体感信号是 对于中风后操作技能的提高和灵活性的恢复至关重要。完成本提案 将识别感觉运动系统内的节点和功能相互作用，这些节点和功能相互作用可以针对新的 改善中风后手部功能恢复的疗法。 我将在卡鲁内什博士领导的杰出指导团队的指导下完成这些目标 Ganguly 博士，包括 Joni Wallis 博士、Robert Morecraft 博士和 Aaron Suminski 博士。在辅导阶段 在获得加州大学旧金山分校的奖项后，我将开发一种最先进的高通道数、多区域电生理学 监测感觉运动网络的方法。我还将在动物身上进行拟议的实验 执行物体操作任务，试点触觉脑机接口任务，并专注于专业 发展，以促进成功过渡到学术界的独立教职职位 机构。