Modulating Low-Frequency Cortical Population Dynamics to Augment Motor Function After Stroke

项目摘要 中风是美国运动残疾的主要原因，每年约有700，000例新发病例。 年手和手指控制能力受损是这种残疾的主要原因。尽管在任务方面取得了进展- 针对上肢的专项训练，大量脑卒中患者不能完全恢复其手功能; 迫切需要新的治疗方法。我们建议使用系统神经科学和“神经 工程的框架，捕捉神经元和分布式电机之间的动态相互作用 网络，以表征和开发新的基于神经生理学的神经调节方法， 增强运动功能。对健康动物的研究支持了一个框架， 局部和远距离区域通过瞬态振荡。振荡由频率带宽定义，例如， 已知运动区具有与任务相关的低频振荡（0.5-4 Hz）。恢复过程如何 影响灵长类动物执行灵巧任务的神经活动和振荡动力学仍然未知？ 我们最近在大鼠中的研究（Ramanathan等人，Nature Medicine 2018; Lemke等人，自然神经科学， 2019）表明，与低频振荡活动（0.5- 4 Hz“LFO”）相关的种群动态是 对于运动控制、跟踪自发恢复至关重要，并且可以作为使用 电刺激更具体地说，皮层刺激被发现既能提高LFO功率， 运动功能基本的翻译步骤包括测试这种方法是否也适用于旋转的 大脑在执行灵巧任务时的反应。 该建议旨在使用体内电生理方法来模拟恢复的网络动力学。 潜在的假设是，病灶周围皮质中的同步LFO尖峰场相互作用是 对恢复很重要，其调节可以增强灵巧运动功能。重要的是，我们的初步 数据为我们提出的研究目标提供了强有力的支持;我们发现，低频振荡 动力学驱动恢复期间感觉和运动区域的协调， 电刺激可以在恢复期间促进灵巧功能。 这些目标的完成将为设计治疗方法提供关键信息， 用低频电刺激靶向病灶周围振荡活动。专注于目标 这种动态网络相互作用的神经调节代表了一个新的方向，可以改变我们的神经系统。 中风后增强上肢功能的能力。

PROJECT SUMMARY Stroke is the leading cause of motor disability in the United States, with approximately 700,000 new cases per year. Impaired hand and finger control are a leading cause of such disability. Despite advances in task- specific training for the upper limb, a large number of stroke patients do not regain full function of their hand; novel treatment methods are urgently required. We propose to use a systems neuroscience and `neural engineering' framework that captures the dynamic interactions between neurons and the distributed motor network to both characterize and develop novel neurophysiological based neuromodulation approaches to enhance motor function. Studies in healthy animals support a framework for dynamic interactions between local and distant areas through transient oscillations. Oscillations are defined by a frequency bandwidth, e.g. motor areas are known to have task-related low-frequency oscillations (0.5-4 Hz). How the recovery process affects neural activity and oscillatory dynamics in primates preforming dexterous tasks remains unknown? Our recent studies in rats (Ramanathan et al., Nature Medicine 2018; Lemke et al., Nature Neuroscience, 2019) demonstrated that population dynamics linked to low-frequency oscillatory activity (0.5-4Hz “LFO”) are essential for movement control, track spontaneous recovery and can serve as a target for modulation using electrical stimulation. More specifically, cortical stimulation was found to both boost LFO power and augment motor function. Essential translational steps involve testing whether this approach also works for gyrated brains during the performance of dexterous tasks. This proposal aims to use in vivo electrophysiological methods to model the network dynamics of recovery. The underlying hypothesis is that synchronous LFO spike-field interactions in the perilesional cortex are important for recovery and its modulation can augment dexterous motor function. Importantly, our preliminary data provides strong support for our proposed research goals; we have found that low-frequency oscillatory dynamics drive coordination of sensory and motor areas during recovery and that artificial low-frequency electrical stimulation can boost dexterous function during recovery. Completion of these aims will provide critical information for designing therapeutic approaches that specifically target perilesional oscillatory activity with low frequency electrical stimulation. Focusing on targeted neuromodulation of such dynamic network interactions represents a new direction that could transform our ability to augment upper extremity function following stroke.