Neuromodulation approaches for restoring dexterous control following cortical stroke.

用于恢复皮质中风后灵巧控制的神经调节方法。

• 批准号: 10223162
• 负责人: Preeya Khanna
• 金额: $ 0.01万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2021-09-02
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10223162
• 关键词: Activities of Daily Living; Affect; Anatomy; Anterior; Area; Automobile Driving; Behavioral; Bilateral; Biological Markers; Brain; Cessation of life; Chronic; Clinic; Data; Development; Dimensions; Electric Stimulation; Electrical Engineering; Electrodes; Electrophysiology (science); Engineering; Exhibits; Feedback; Fellowship; Frequencies; Goals; Hand; Human; Implant; Injury; Knowledge; Left; Lesion; Link; Medicine; Methods; Modeling; Monitor; Motor; Motor Cortex; Nature; Neurosciences; Operative Surgical Procedures; Pattern; Perception; Performance; Phase; Physical therapy; Population Dynamics; Primates; Rattus; Recovery; Research; Research Personnel; Space Models; Stroke; Study models; Survivors; System; Testing; Therapeutic; Time; Training; United States; Upper Extremity; Upper arm; Work; base; design; dexterity; disability; dynamic system; grasp; hand dysfunction; hand rehabilitation; improved; innovation; materials science; model design; multi-scale modeling; neural network; neural patterning; neurophysiology; neuroregulation; nonhuman primate; novel; programs; relating to nervous system; response; restoration; skills; somatosensory; stroke survivor; therapeutic target

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. One of many predictors of chronically impaired hand function includes deficits in somatosensation. Here, we propose to use a systems neuroscience and `neural engineering' framework that captures dynamic interactions across somatosensory and distributed motor networks to develop novel neurophysiological based neuromodulation to enhance motor function. The recent study, Ramanathan et al., Nature Medicine 2018, in rats recovering from a stroke demonstrated that population dynamics linked to low-frequency oscillatory activity (0.5-4Hz “LFO”) tracked spontaneous recovery and cortical stimulation boosted LFO power and could also augment motor function. Essential translational steps involve testing whether this approach also works for gyrated brains during the performance of dexterous tasks. The main experimental approach of this proposal involves monitoring motor and somatosensory activity during dexterous control in unaffected and affected hemispheres of non-human primates (NHPs) following recovery from a unilateral cortical lesion. Linear state space models will be used to describe neural activity progression in perilesional motor cortices, and used to model the effects of somatosensory inputs on motor state. These models will be used to identify markers of when low-frequency network dynamics need strengthening in the recovery phase and chronic deficit phase. Informed by the models, both open-loop and closed-loop low- frequency cortical stimulation will be tested to determine if dexterity improves. Completion of these aims will provide critical models for designing therapeutic approaches that specifically target perilesional oscillatory activity with low frequency electrical stimulation, a new direction that could transform our ability to augment upper extremity function following stroke. In this fellowship period, additional training will be needed in primate anatomy and electrophysiology, creation of injury models in primates, and in material science and electrical engineering related to the design of a neuromodulation system. These areas of knowledge and skills are necessary for completion of the proposed aims, as well as development of an independent research program following the fellowship period. Finally, all work will take place at UCSF, renowned for its lab-to-clinic translational work and training of independent investigators.

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。 尽管有物理疗法，但大约50％的中风存活率受到了手部功能的障碍，这对 日常生活和独立的活动；迫切需要新颖的治疗方法。众多 长期受损的手部功能的预测因素包括体感应中的定义。在这里，我们建议使用 系统的神经科学和“神经工程”框架，可捕获各种动态互动 体感和分布的运动网络，以开发新的基于神经生理的神经调节 增强运动功能。最近的研究，Ramanathan等人，《自然医学2018》，在从A中恢复过来的大鼠 中风表明，跟踪的低频振荡活动（0.5-4Hz“ LFO”）相关的种群动态 赞助的恢复和皮质刺激增强了LFO功率，还可以增强运动功能。 基本的翻译步骤涉及测试这种方法是否也适用于旋转的大脑 灵巧任务的执行。 该提案的主要实验方法涉及监测电动机和体感活动 在非人类灵长类动物（NHP）的未受影响和影响半球的灵巧控制过程中 从单侧皮质病变中恢复。线性状态空间模型将用于描述神经活动 周围运动皮层的进展，用于对体感觉输入对运动态的影响进行建模。 这些模型将用于确定低频网络动态需要加强的标记 恢复阶段和慢性缺陷阶段。由模型的开环和闭环低 - 将测试频率皮质刺激，以确定敏度是否有所改善。这些目标的完成将 提供设计治疗方法的关键模型，这些方法专门针对周期振荡活动 使用低频电气模拟，可以改变我们增强上部能力的新方向 中风后肢体功能。 在这个研究金期间，灵长类解剖学和电生理学需要额外的培训， 与设计有关的材料科学和电气工程中的伤害模型 神经调节系统。这些知识和技能领域对于完成拟议的领域是必需的 奖学金期之后的目标以及对独立研究计划的制定。最后，一切 工作将在UCSF举行，以其实验室到临床的翻译工作和独立培训而闻名 调查人员。