Collaborative Research: NCS-FO: Intelligent Closed-Loop Neural Interface System for Studying Mechanisms of Somatosensory Feedback in Control of Functional and Stable Locomotion

合作研究：NCS-FO：智能闭环神经接口系统，用于研究体感反馈控制功能性和稳定运动的机制

• 批准号: 2024270
• 负责人: Wen Li
• 金额: $ 39万
• 依托单位: Michigan State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2024270&HistoricalAwards=false
• 关键词: Collaborative; Research; NCS; FO; Intelligent

Sensory feedback from moving legs is critical for functional and dynamically stable locomotion. Although it is clear that motion-related sensory feedback influences inter-leg coordination and selection of gaits (walking, trotting, galloping, etc.), it is not known which sensory modalities (e.g., muscle length- or force-related signals) and sources of feedback (e.g., hip or knee muscles) mediate these locomotor changes. Therefore, this project aims to understand how sensory neurons providing information about the length of hip muscles regulate interlimb coordination and gait selection. This goal will be accomplished by selectively and reversibly stimulating these sensory neurons in an intelligent, closed-loop, and well-controlled manner. This project will lead to the development of new neural implant tools and associated computational algorithms for an in-vivo manipulation of motion-related sensory signals in a large animal model, the cat. The new findings of this project and the developed methods will substantially enhance our understanding of the mechanisms of sensory locomotor control and contribute to developing novel therapeutic interventions. The proposed multidisciplinary research approaches will also significantly expand the utility and capabilities of the rapidly growing field of optogenetics, enabling transformative research and providing unprecedented new experimental tools for neuroscience. The most noticeable long-term benefits of this work to society will be an improvement in the quality of life for a sizable population of people affected by a wide range of movement deficits, from limb loss to sensory neuropathy. These individuals will benefit from the development of neural interfaces between the nervous and engineering systems controlled by machine learning algorithms. Throughout this project, efforts will be made to recruit and train graduate and undergraduate students from underrepresented groups. Outreach activities will also be organized to share resources, tools, and knowledge with teachers, students, and underrepresented groups. The results of the proposed research and educational activities will be shared with students, scientific communities, and the public through science fairs, publications, workshops, conferences, and the Internet.The overall goal of this proposal is to characterize the mechanisms of somatosensory control of interlimb coordination and gait selection by spindle afferents of hip muscles in the cat model by developing and utilizing in-vivo an intelligent and closed-loop optoelectronic neural interface system. In particular, in this proposal high-density, efficient, and wirelessly-powered implantable opto-electro (WIOE) neural interface devices will be developed. Each WIOE heterogeneously incorporates an optoelectronic array of 64 transparent microelectrodes and 16 microscale light-emitting-diodes (µLEDs), a system-on-a-chip (SoC), and a power receiver (Rx) coil in an mm3-size package, capable of optogenetic stimulation and electrical recording of neural activities. Wireless telemetry links will be implemented for efficient transcutaneous power and wideband data transmission between an external data-acquisition/control unit and the distributed array of WIOE implants. Multiple WIOE devices will be implanted in selected dorsal root ganglia (DRG) of the cat. Neural activities of DRG neurons, EMG activities of selected muscles of the four limbs, and full-body locomotor kinematics will be recorded, and spindle afferent activities will be manipulated via optogenetic stimulation in selected DRGs during unconstrained cat locomotion. Machine learning (ML) models leveraging the spatiotemporal structures in the signals and mapping afferent activities in DRGs to limb kinematics will be applied for achieving closed-loop control of the optogenetic neuromodulation. The proposed research activities will be conducted by a team of collaborators with complementary research expertise in the areas of bioMEMS, wireless microelectronics, machine learning, artificial intelligence, and behavioral neuroscience. The successful development of the proposed intelligent and closed-loop optoelectronic neural interface will yield a robust building block for a comprehensive set of minimally invasive neural interfaces to study somatosensory control of movement, as well as monitor or treat somatosensory pathological conditions.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

移动腿部的感觉反馈对于功能性和动态稳定的运动至关重要，尽管很明显，与运动相关的感觉反馈会影响腿间协调和步态选择（步行、小跑、驰骋等），但尚不清楚是哪种感觉反馈。因此，该项目旨在了解感觉神经元如何提供有关运动的信息。臀部肌肉的长度调节四肢间的协调和步态选择，将通过以智能、闭环和良好控制的方式选择性地、可逆地刺激这些感觉神经元来实现。该项目将导致新的神经植入工具的开发。以及用于在大型动物模型（猫）中体内操纵与运动相关的感觉信号的相关计算算法，该项目的新发现和开发的方法将大大增强我们对感觉运动控制机制的理解，并有助于开发新的治疗干预措施。所提出的多学科研究方法还将显着扩展快速发展的光遗传学领域的实用性和能力，从而实现变革性研究并为神经科学提供前所未有的新实验工具。这项工作对社会最显着的长期好处将是改善。受从肢体丧失到感觉神经病等各种运动缺陷影响的大量人群的生活质量将受益于整个项目中由机器学习算法控制的神经系统和工程系统之间的神经接口的开发。 ，将努力还将组织招募和培训来自代表性不足群体的研究生和本科生，以与教师、学生和代表性不足的群体共享资源、工具和知识。拟议的研究和教育活动的结果将与学生、科学界共享。通过科学博览会、出版物、研讨会、会议和互联网向社区和公众提供信息。该提案的总体目标是描述猫髋部肌肉纺锤体传入对肢体间协调和步态选择的体感控制机制通过开发和利用体内智能闭环光电神经接口系统，特别是在该提案中，将开发高密度、高效、无线供电的可植入光电（WIOE）神经接口设备。 WIOE 异构地整合了由 64 个透明微电极和 16 个微型发光二极管 (μLED) 组成的光电阵列，这是一种片上系统(SoC) 和采用 mm3 尺寸封装的功率接收器 (Rx) 线圈，能够实现神经活动的光遗传学刺激和电记录，以实现外部数据采集之间的高效经皮功率和宽带数据传输。 /控制单元和WIOE植入物的分布式阵列将被植入猫的选定的背根神经节（DRG）中 DRG神经元的神经活动、选定的四块肌肉的EMG活动。在无约束的猫运动过程中，机器学习（ML）模型将利用信号中的时空结构并将 DRG 中的传入活动映射到特定 DRG 中，通过光遗传学刺激来操纵主轴传入活动。肢体运动学将用于实现光遗传学神经调节的闭环控制。拟议的研究活动将由具有互补研究的合作者团队进行。所提出的智能闭环光电神经接口的成功开发将为一套全面的微创神经接口提供强大的构建模块。研究运动的体感控制，以及监测或治疗体感病理状况。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力价值和更广泛的影响审查进行评估，被认为值得支持标准。

项目成果

A FLEXIBLE ORIGAMI OPTO-ELECTRO ARRAY FOR IN VIVO OPTOGENETIC STIMULATION AND ELECTROPHYSIOLOGY RECORDINGS FROM DORSAL ROOT GANGLION

用于体内光遗传学刺激和背根神经节电生理学记录的灵活折纸光电阵列

• 发表时间: 2022-06
• 期刊: and Microsystems Workshop
• 作者: Yan Gong; Xiang Liu
• 通讯作者: Xiang Liu

A Wireless Implantable Opto-Electro Neural Interface ASIC for Simultaneous Neural Recording and Stimulation

用于同步神经记录和刺激的无线植入式光电神经接口 ASIC

• DOI: 10.1109/cicc57935.2023.10121181
• 发表时间: 2023-04-01
• 期刊: 2023 IEEE Custom Integrated Circuits Conference (CICC)
• 作者: Linran Zhao;Yan Gong;Wei Shi;R. Stephany;Wen Li;Y. Jia
• 通讯作者: Y. Jia