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.

项目摘要 引起中风的疾病，残疾和早期死亡将在未来15年内在全球范围内两倍。尽管 物理疗法，大约50％的中风幸存者的手部功能受损，这对活动产生了强烈影响 日常生活和独立性；迫切需要新颖的治疗方法。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降运动途径， 灵巧的手功能也依赖于大脑接收上升的体感输入，并能够 使用它来指导运动。在临床和动物模型中，体感皮质的缺陷预测更糟 中风后手功能的恢复，尽管功能机制是体感信号的 支撑手功能的特征仍然很差。在此提案中，我们旨在发现体感如何 信号驱动电动机活动在完整的灵活操纵行为的获取和性能期间 和中风后非人类灵长类动物。 该提案的主要实验方法包括同时高密度，高通道计数 体感丘脑，原发性体感皮质和急性电生理记录 一级运动皮层完整和中风后非人类灵长类动物执行复杂的操纵任务。这 主要分析方法包括将运动活动演变建模为内在运动皮质的组合 体感丘脑和体感皮质的动力和输入。该提议的假设 是体感输入信号指导有效运动活动轨迹的识别 经常使用，较少依赖于改进的操纵技巧。因此，体感信号是 在改善操纵技巧和恢复后，中风后的恢复至关重要。完成此提案 将在感觉运动系统内识别可以针对新颖的节点和功能相互作用 中风后改善手部功能恢复的疗法。 我将在Karunesh博士领导的一支杰出指导团队的指导下完成这些目标。 Ganguly，包括Joni Wallis博士，Robert Morecraft博士和Aaron Suminski博士。在指导阶段 在UCSF的奖项中，我将开发一个最先进的高渠道计数多区域生理学 监视感觉运动网络的方法。我还将在动物中进行拟议的实验 执行对象操纵任务，驾驶触觉脑机插头任务并专注于专业 为了促进在学术上成功过渡到独立教师职位的发展 机构。