LFP-Driven Activity-Dependent Stimulation Techniques for Acquired Brain Injury

LFP 驱动的活动依赖性刺激技术治疗获得性脑损伤

• 批准号: 9405809
• 负责人: David Thomas Bundy
• 金额: $ 6.19万
• 依托单位: UNIVERSITY OF KANSAS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9405809
• 关键词: Action Potentials; Address; Algorithms; Animal Model; Animals; Behavior; Behavioral; Brain Injuries; Brain region; Caring; Chronic; Chronic Brain Injury; Clinical; Development; Electrophysiology (science); Future; Goals; Injury; Intervention; Knowledge; Laboratories; Lesion; Longevity; Measures; Medical; Microelectrodes; Motor; Motor Cortex; Movement; Nervous system structure; Neuraxis; Neuronal Plasticity; Neurons; Outcome; Pathway interactions; Pattern; Performance; Population; Protocols documentation; Public Health; Rattus; Recovery; Research; Rodent; Rodent Model; Sensory; Signal Transduction; Site; Somatosensory Cortex; Stimulus; Stroke; Survivors; System; Techniques; Testing; Therapeutic; Translating; Translations; Traumatic Brain Injury; Work; awake; design; disability; effective therapy; functional improvement; functional restoration; improved; innovation; microdevice; motor function improvement; motor function recovery; neuroprosthesis; novel; novel therapeutics; patient population; relating to nervous system; repaired; stem; success

PROJECT SUMMARY/ABSTRACT Substantial reorganization occurs throughout spared brain regions following stroke or traumatic brain injury. These neuroplastic mechanisms are thought to underlie functional behavioral recovery, but our understanding of the electrophysiological activity associated with this reorganization is incomplete. Characterizing the changes in neural activity during recovery from brain injury would allow us to better target and develop new therapies. One such therapy that has been recently proposed is activity-dependent stimulation (ADS), designed to artificially connect two sites within the nervous system. Our long-term goal is to understand the mechanisms of ADS that drive functional improvements after cortical lesions in order to translate ADS paradigms into clinical populations. The overall objective for the current project is to determine how patterns of local field potential (LFP) signals change during recovery from brain injury, how these signals are altered through ADS, and to determine if they can be used effectively to trigger ADS and drive behavioral recovery. Specifically, our central hypothesis is that the movement-related spectral power and functional connectivity of LFP signals are dysfunctional after brain injury and will be normalized after either recovery or ADS. The rationale for the proposed research is that the LFP changes that occur after a brain injury and after single-unit driven ADS, will be pathway-specific candidate features for LFP-triggered ADS algorithms. While single-unit driven ADS has shown benefits in a rodent model of brain injury, success demonstrating that LFP signals can be used to drive ADS paradigms in animal models may result in more effective translation into patient populations due to the increased longevity of LFP-driven interfaces. We will seek to accomplish these goals through the following specific aims: 1) identify alterations in movement-related spectral power changes and movement-related functional connectivity that occur in LFP signals after a cortical lesion; 2) identify alterations in movement-related spectral power changes and functional connectivity that occur after single-unit triggered ADS in brain-injured animals; and 3) demonstrate the ability to use LFP-triggered ADS to generate changes in functional connectivity. We will test these aims using chronic recordings in awake behaving healthy rodents, brain-injured rodents, and brain-injured rodents undergoing an ADS protocol. Additionally, we will use chronic LFP-driven ADS paradigms to determine if these algorithms can alter cortical functional connectivity. This project is innovative because it proposes a new paradigm positing that LFP signal components have the fidelity to be used to trigger activity-dependent stimulation protocols altering cortical connectivity. Furthermore, this project is significant because it will generate a greater understanding of the dynamics of neural activity associated with motor behavior after a brain injury and with recovery of motor function.

项目总结/摘要 在中风或创伤性脑损伤后，整个备用脑区域都发生了实质性的重组。 这些神经可塑性机制被认为是功能性行为恢复的基础，但我们的理解 与这种重组相关的电生理活动是不完整的。表征 脑损伤恢复期间神经活动的变化将使我们能够更好地瞄准和开发新的 治疗最近提出的一种这样的疗法是活动依赖性刺激（ADS）， 人工连接神经系统内的两个部位我们的长期目标是了解 ADS的机制，驱动皮质病变后的功能改善，以翻译ADS 应用到临床人群中。本项目的总体目标是确定 局部场电位（LFP）信号在脑损伤恢复过程中发生变化，这些信号是如何改变的 通过ADS，并确定它们是否可以有效地用于触发ADS和驱动行为恢复。 具体来说，我们的中心假设是，运动相关的光谱功率和功能连接的 LFP信号在脑损伤后功能障碍，并且在恢复或ADS后将正常化。的 拟议研究的基本原理是，脑损伤后和单一单位后发生的LFP变化 驱动的ADS，将是特定于路径的候选特征，用于LFP触发的ADS算法。当单个单元 驱动的ADS已在啮齿动物脑损伤模型中显示出益处，成功证明LFP信号可以 用于在动物模型中驱动ADS范例可能会导致更有效地转化为患者 由于LFP驱动接口的寿命增加，我们将努力实现这些目标 通过以下具体目的：1）识别与运动相关的光谱功率变化的改变， 皮质损伤后LFP信号中发生的运动相关功能连接; 2）识别改变 在与运动相关的频谱功率变化和功能连接中， 在脑损伤动物中的ADS;和3）证明使用LFP触发的ADS产生脑损伤动物中的变化的能力。 功能性连接。我们将使用清醒行为的健康啮齿动物的长期记录来测试这些目标， 脑损伤的啮齿类动物和经历ADS方案的脑损伤的啮齿类动物。此外，我们将使用慢性 LFP驱动的ADS范例，以确定这些算法是否可以改变皮质功能连接。这 该项目是创新的，因为它提出了一个新的范式，假定LFP信号分量具有保真度 用于触发活动依赖性刺激协议，改变皮层连接。而且这 这个项目意义重大，因为它将使我们对神经活动的动力学有更深入的了解 与脑损伤后的运动行为和运动功能的恢复相关。