The future of brain research lies in the application of new technologies drawing from the latest developments in biology, physics and engineering to advance our understanding of how this complex organ processes, integrates and transfers information. Among these, optogenetics is a groundbreaking technology that allows using light to selectively activate neurons in the cortex of transgenic animals, usually mice, to observe its effect in large biological networks. A new research paradigm drawing from these advances consists of synchronizing optogenetic stimulation with electrophysiology recordings, to close the loop and to regulate the neural microcircuits, or to repair them. Such an approach holds promise to accelerate the development of new therapeutics against brain diseases by enabling entirely new experimental research scenarios with freely behaving animal models. As a result, the development of advanced wireless microelectronic implantable systems to elicit, extract and process brain data in real time has become a source of significant interest. This paper reviews the design challenges and the state-of-the-art technology in this field. We present the design of a complete electro-optic device for preforming optogenetics and multichannel electrophysiology in a closed-loop (CL) system with live neurons. We cover the design of the different CMOS integrated building blocks involved in this system to perform photostimulation and multichannel neural recording in parallel. We describe advanced hardware strategies to perform action potential (AP) detection, neural data compression and AP sorting in real-time, over several parallel recording channels for enabling real-time CL neural control. Finally, we present CL experimental results obtained in vivo with an electro-optic prototype.

中文翻译：

---

智能自主电光平台支持创新的大脑疗法

大脑研究的未来在于应用从生物学、物理学和工程学的最新发展中汲取的新技术，以推进我们对这个复杂器官如何处理、整合和传递信息的理解。其中，光遗传学是一项开创性技术，它允许使用光选择性激活转基因动物（通常是小鼠）皮层中的神经元，以观察其在大型生物网络中的作用。从这些进展中汲取的新研究范式包括将光遗传学刺激与电生理记录同步，以关闭回路并调节神经微电路或修复它们。这种方法有望通过使用自由行为的动物模型实现全新的实验研究场景，从而加速开发针对脑部疾病的新疗法。因此，开发先进的无线微电子植入式系统以实时获取、提取和处理大脑数据已成为一个重要的兴趣来源。本文回顾了该领域的设计挑战和最先进的技术。我们提出了一个完整的电光设备的设计，用于在具有活神经元的闭环 (CL) 系统中进行光遗传学和多通道电生理学。我们介绍了该系统中涉及的不同 CMOS 集成构建块的设计，以并行执行光刺激和多通道神经记录。我们描述了通过多个并行记录通道实时执行动作电位 (AP) 检测、神经数据压缩和 AP 排序的高级硬件策略，以实现实时 CL 神经控制。最后，我们展示了使用电光原型在体内获得的 CL 实验结果。