Smart Dura: A Functional Large-scale, High-Density Optoelectric Dura for Non-Human Primates

智能硬脑膜：用于非人类灵长类动物的功能性大型高密度光电硬脑膜

• 批准号: 10440410
• 负责人: Maysamreza Chamanzar
• 金额: $ 48.31万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-15 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10440410
• 关键词: Address; Adhesions; Advanced Development; Animal Model; Animals; Area; Behavior; Behavioral; Brain; Calcium; Cephalic; Chronic; Communication; Complex; Coupled; Deposition; Development; Device or Instrument Development; Dura Mater; Electrocorticogram; Electrodes; Electronics; Electrophysiology (science); Engineering; Equilibrium; Equine mule; Fiber; Future; Head; Human; Hybrids; Image; Implant; Investigation; Light; Macaca; Mechanics; Microfabrication; Modeling; Monitor; Monkeys; Morphologic artifacts; Mus; Neuronal Plasticity; Neurons; Opsin; Optical Coherence Tomography; Optics; Pattern; Performance; Process; Public Health; Publishing; Reporting; Resolution; Site; Source; Stroke; Structure; Surface; System; Techniques; Technology; Testing; Time; Translating; Virus; awake; base; biocompatible polymer; biomaterial compatibility; cell type; density; design; experimental study; flexibility; imaging modality; indium tin oxide; insight; interest; lithography; millisecond; multi-photon; multimodal data; nervous system disorder; neural circuit; neural network; neurophysiology; nonhuman primate; novel; novel therapeutic intervention; optical fiber; optogenetics; parylene C; polydimethylsiloxane; pressure; prevent; relating to nervous system; stroke recovery; success; temporal measurement; tool; tool development

Project Summary Optogenetics is a powerful tool for relating brain function to behavior because it enables cell- type specific manipulation of neurons with millisecond temporal precision and artifact-free neural recordings. Such capabilities are particularly needed in studies using non-human primates (NHPs), where sophisticated behavioral techniques are commonly employed but neurophysiological tools have lagged those used in other model species. While the use of optogenetics in NHPs has grown rapidly in recent years, the full power of the technique requires the ability to perform large-scale, bi-directional study of neural circuits. Systems to achieve this have become widely used in other animal models, particularly mice, while there have been limited systems implemented in NHPs. In this proposal, a large-scale, high-density, and stable optoelectric neural interface (smart dura) for large brains will be developed and validated in macaques, for the first time. This novel interface enables simultaneous electrical recording from 4096 electrodes and optical stimulation in 4096 sites over about 5 cm2 of cortex, which is more than two orders of magnitude higher than the state-of-the-art technology. As opposed to existing surface electrocorticography (ECoG) electrode arrays, the proposed neural interface is in the form of an artificial dura that monolithically embeds electrical recording and optical stimulation functionalities such that it can permanently replace the native dura as a chronic, seamless neural interface, while maintaining the natural cranial pressure. Therefore, this novel design combines the best of passive/static artificial dura windows and functional surface electrode arrays in one unified platform. The proposed smart dura enables long-term recording, provides new opportunities for creating sophisticated closed-loop stimulation and recording paradigms, and advances the development of new stimulation-based therapies. The smart dura can be implanted as a stable port into large brains and consists of high-density recording electrodes as well as optical micro light sources all embedded in a hybrid biocompatible polymer platform. In this project, a novel fabrication process will be designed to implement the proposed large-scale (5 cm2) smart dura in two stages of: i) Fabricating high-density transparent electrical smart dura for electrophysiology recording and external optical access (transparent electric dura: transparent e- dura), enabled by high resolution interconnects (300 nm features). ii) The optoelectric dura (oe- dura) consisting of high-density recording electrodes and embedded micro light emitting diodes (µLEDs). In each stage of the device development, the neural interface will be tested in two hemispheres of two monkeys, with large optogenetic expression of activating opsin (ChR2) in sensorimotor cortex via electrophysiology recording, behavior, and imaging. The proposed smart dura will greatly enhance the opportunities for closed-loop optogenetic experiments in macaques, which can serve as a powerful tool for understanding brain function and for developing novel therapeutic interventions that can be translated to humans. After successful demonstration of the smart dura in this proposal, the results can be extended in future to i) develop even larger interfaces that cover the whole brain for translational use ii) integrate recording, stimulation, processing, communication and power-transfer electronics into the smart dura to enable tetherless chronic neural interfacing with freely-moving subjects.

项目摘要 光遗传学是将大脑功能与行为联系起来的强大工具，因为它可以使细胞 - 用毫秒临时精度和无伪影神经元对神经元的特定操纵类型 录音。在使用非人类隐私的研究中，这种功能尤其需要 （NHP），通常采用复杂的行为技术，但 神经生理工具落后于其他模型物种。而使用 NHP中的光遗传学近年来迅速增长，该技术的全部功能需要 对神经回路进行大规模，双向研究的能力。实现这一目标的系统 在其他动物模型，尤其是小鼠中已广泛使用，虽然有限 NHPS实施的系统。在此提案中，大规模，高密度和稳定 将开发和验证用于大脑的光电神经接口（智能硬脑膜） 猕猴，第一次。这个新颖的界面可以同时从 4096个在约5 cm2的皮质上的4096个位点的电极和光刺激，这更多 比最先进的技术高两个数量级。而不是现有 表面电视学（ECOG）电极阵列，提出的神经界面以形式形式 单层嵌入电记录和光学刺激的人造硬脑膜 功能使其可以永久替代本地硬脑膜作为慢性无缝神经 界面，同时保持自然颅压。因此，这种新颖的设计组合 最好的被动/静态人造硬脑膜窗和功能性表面电极阵列 统一平台。拟议的智能硬脑膜可实现长期录制，提供新的 创建复杂的闭环刺激和记录范例的机会，以及 促进新的基于刺激的疗法的发展。可以植入智能的硬脑膜 作为大脑中的稳定端口，由高密度记录电极以及 光学微光源都嵌入混合生物相容性聚合物平台中。在这个 项目，将设计一个新颖的制造过程来实施拟议的大规模（5 CM2）智能硬脑膜分为两个阶段： 电生理记录和外部光学获取（透明电力硬脑膜：透明的E- 硬脑膜），由高分辨率互连（300 nm功能）启用。 ii）光电硬脑膜（OE-） 硬脑膜）由高密度记录电极和嵌入式微光发射二极管组成 （µleds）。在设备开发的每个阶段，神经界面将在两个中进行测试 两只猴子的半球，在激活OPSIN（CHR2）中具有较大的光遗传学表达 通过电生理记录，行为和成像的感觉运动皮层。拟议的智能 硬脑膜将大大增强猕猴中闭环光遗传学实验的机会， 它可以作为理解大脑功能和发展新颖的强大工具 可以转化为人类的治疗干预措施。成功演示了 在该提案中，智能硬脑膜可将来扩展到i）发展更大 覆盖整个大脑以进行翻译的接口ii）集成记录，刺激， 处理，通信和电力转移电子设备进入智能硬脑膜以启用 与自由移动主题的无限慢性神经接口。