3D multifunctional deep brain interface for seizure detection and intervention

用于癫痫发作检测和干预的 3D 多功能深部脑接口

• 批准号: 10456940
• 负责人: Xiaoting Jia
• 金额: $ 38.48万
• 依托单位: VIRGINIA POLYTECHNIC INST AND ST UNIV
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10456940
• 关键词: 3-Dimensional; Address; Affect; Animal Model; Animals; Biochemical; Biomechanics; Brain; Brain region; Caliber; Chemicals; Chronic; Clinical; Detection; Development; Devices; Disease; Distant; Drug Delivery Systems; Drug Regulations; Electrodes; Electroencephalogram; Electrophysiology (science); Elements; Engineering; Epilepsy; Fiber; Future; Goals; Histocompatibility; Histology; Human; Image; Implant; Intervention; Lasers; Maps; Mechanics; Mental disorders; Methods; Mus; Operative Surgical Procedures; Optics; Parkinson Disease; Patients; Performance; Persons; Pharmaceutical Preparations; Pharmacological Treatment; Polymers; Regulation; Research; Resolution; Rotation; Saline; Sampling; Seizures; Site; Slice; Specificity; Spectrum Analysis; Surface; Technology; Testing; Time; Tissues; Transgenic Mice; Trephine hole; Virus; Work; base; biomaterial compatibility; brain tissue; clinically relevant; design; effective therapy; electric impedance; experimental study; extracellular; in vivo; insight; millimeter; minimally invasive; mouse model; nervous system disorder; neuropsychiatry; novel; novel therapeutic intervention; optogenetics; patient population; relating to nervous system; response; side effect; spatiotemporal; success; temporal measurement; tool

Project Summary/Abstract: Treatment of neurological disorders and psychiatric diseases, such as epilepsy, remains a big clinical challenge in large populations of patients. A fundamentally more effective treatment method requires a thorough understanding of the functional networks in the brain. This endeavor, however, critically relies on the engineering success of building a deep brain interface that mimics brain complexity and is also compatible with brain tissues. A key challenge in current neural interface devices is to map and modulate the brain dynamics over a large volume in deep brain while providing a high spatiotemporal resolution and maintaining minimal tissue damage. Our primary goal is to address this challenge by developing a spatially expandable fiber-based neural probe as a multifunctional deep brain interface. The central hypotheses in this project are: (1) The spatially expandable fiber-based probe arrays can provide a minimally invasive 3D interface to achieve biomechanical and biochemical compatibility with brain tissue, as well as to enable large volume stimulation and recording with a high spatiotemporal resolution; (2) The probe arrays allow for more precise detection of seizure foci compared with existing methods, and enable real time suppression of seizure activities by localized optogenetic and drug regulation. The specific aims of this project are: (1) Develop spatially expanded fiber-based probe arrays for multifunctional in vivo neural interfacing; (2) Elucidate the electrical recording, optical stimulation, and drug delivery performance of the probe arrays in vivo and the tissue response of the probe arrays; (3) Demonstrate seizure foci detection and real-time seizure suppression using localized drug and optogenetic intervention in deep brain. The hypotheses and aims will be tested using a clinically relevant animal model of virus-induced seizure in mouse employing a combination of electrophysiology, optogenetics, and focal drug delivery in vivo, as well as imaging and histology in brain slices. This technology can provide a powerful tool for advancing the fundamental study of the microcircuitry and functional networks in both animal and human brains. In the future, these studies have the potential to elucidate novel ways to detect and treat neurological diseases at an early stage and more effectively compared to other existing methods.

项目摘要/摘要： 神经系统疾病和精神疾病（例如癫痫）的治疗仍然是一个重要的临床领域 大量患者面临的挑战。一种从根本上更有效的治疗方法需要 深入了解大脑的功能网络。然而，这一努力关键依赖于 构建模仿大脑复杂性且兼容的深层大脑接口的工程成功 与脑组织。当前神经接口设备的一个关键挑战是映射和调节大脑 大脑深部大体积的动力学，同时提供高时空分辨率并保持 最小的组织损伤。我们的主要目标是通过开发一个空间解决方案来应对这一挑战 可扩展的基于纤维的神经探针作为多功能深部大脑接口。中心假设 该项目的特点是：（1）空间可扩展的基于光纤的探针阵列可以提供微创3D 接口以实现与脑组织的生物力学和生化兼容性，以及使大 高时空分辨率的容量刺激和记录； (2) 探针阵列允许更多 与现有方法相比，可以精确检测癫痫病灶，并能够实时抑制癫痫发作 局部光遗传学和药物调节的活性。本项目的具体目标是：（一）发展 用于多功能体内神经接口的空间扩展的基于光纤的探针阵列； (2) 阐明 探针阵列在体内的电记录、光刺激和药物输送性能以及 探针阵列的组织响应； (3) 演示癫痫病灶检测和实时癫痫发作抑制 在大脑深部使用局部药物和光遗传学干预。假设和目标将使用以下方法进行测试 病毒诱导小鼠癫痫发作的临床相关动物模型，采用以下组合： 电生理学、光遗传学和体内局部药物递送，以及脑成像和组织学 切片。该技术可以为推进微电路基础研究提供有力的工具 以及动物和人类大脑中的功能网络。未来，这些研究有可能 阐明早期更有效地检测和治疗神经系统疾病的新方法 与其他现有方法相比。