3D multifunctional deep brain interface for seizure detection and intervention

项目摘要/摘要： 治疗神经性疾病和精神疾病，如癫痫，仍然是一个巨大的临床问题。 在庞大的患者群体中面临挑战。一种从根本上更有效的治疗方法需要 彻底了解大脑中的功能网络。然而，这一努力关键依赖于 在工程上成功地构建了一个深层次的大脑接口，它模仿了大脑的复杂性，并且 用脑组织。当前神经接口设备中的一个关键挑战是映射和调节大脑 在提供高时空分辨率的同时保持脑深部大体积的动力学 组织损伤最小。我们的主要目标是通过开发一种空间 作为多功能脑深部接口的可扩展光纤神经探头。中心假说 本课题的主要研究内容有：(1)空间可扩展的光纤探头阵列可以提供微创的3D 接口，以实现与脑组织的生物力学和生化兼容性，以及使 高时空分辨率的体积刺激和记录；(2)探头阵列允许更多 与现有方法相比，可以精确检测癫痫灶，并能够实时抑制癫痫发作 通过局部的光遗传和药物调控的活动。本项目的具体目标是：(1)开发 用于多功能体内神经接口的空间扩展的光纤探针阵列；(2)阐明 探针阵列在体内和体内的电记录、光刺激和药物输送性能 探头阵列的组织响应；(3)显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干预。假设和目标将通过以下方式进行测试 一种临床相关的小鼠病毒诱导癫痫的动物模型 电生理学、光遗传学和体内局部给药，以及脑内的成像和组织学 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发现和治疗神经系统疾病的新方法 与现有的其他方法相比，该方法具有更高的精度。

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.