3D multifunctional deep brain interface for seizure detection and intervention

项目概要/摘要： 治疗神经系统疾病和精神疾病，如癫痫，仍然是一个大的临床 对大量患者的挑战。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，这一奋进主要依赖于 在工程上成功地建立了一个模拟大脑复杂性的深层大脑接口， 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 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 可扩展的基于纤维的神经探针作为多功能脑深部接口。核心假设 （1）空间可扩展的光纤探头阵列可以提供微创的3D 界面，以实现与脑组织的生物力学和生物化学相容性，以及使大的 体积刺激和高时空分辨率记录;（2）探头阵列允许更多 与现有方法相比，精确检测癫痫病灶，并且能够真实的抑制癫痫发作 活性通过局部光遗传学和药物调节。该项目的具体目标是：（1）开发 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 电记录，光刺激，和药物输送性能的探针阵列在体内和 探针阵列的组织反应;（3）演示癫痫灶检测和实时癫痫抑制 在脑深部使用局部药物和光遗传学干预。假设和目标将通过以下方式进行检验： 在小鼠中病毒诱导的癫痫发作的临床相关动物模型，其采用以下的组合： 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 切片该技术为推进微电路的基础研究提供了强有力的工具 以及动物和人类大脑中的功能网络。在未来，这些研究有可能 阐明在早期阶段更有效地检测和治疗神经系统疾病的新方法 与现有的其他方法相比。

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.