A wireless closed-loop sleep modulation system-on-chip

无线闭环睡眠调制片上系统

• 批准号: 10733872
• 负责人: Xilin Liu
• 金额: $ 46.24万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-01 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10733872
• 关键词: Acceleration; Acoustic Stimulation; Address; Affect; Agreement; Amplifiers; Animal Model; Animals; Auditory; Behavior; Biological Models; Bite; Brain; Canis familiaris; Charge; Classification; Communities; Data Analyses; Data Compression; Devices; Disease; Electric Stimulation; Electrophysiology (science); Eye; Family suidae; Felis catus; Health; Home; Housing; Human; Immune; Intervention; Investigation; Label; Learning Module; Light; Macaca; Machine Learning; Metabolic; Modeling; Modification; Monkeys; Mus; Muscle; Neurodegenerative Disorders; Neurons; Noise; Optics; Performance; Phase; Physiological; Physiology; Play; Polysomnography; Process; Qualifying; REM Sleep; Radio; Rattus; Research; Rodent; Role; Running; Scientist; Sensory; Signal Transduction; Silicon; Sleep; Sleep Architecture; Sleep Disorders; Sleep Stages; Specificity; System; Techniques; Technology; Testing; Time; Wakefulness; Weight; algorithm training; analog; cognitive benefits; data acquisition; data exchange; data reduction; design; digital; energy efficiency; experience; experimental study; free behavior; hypocretin; improved; in vivo; in vivo evaluation; industry partner; long term memory; microelectronics; microsystems; miniaturize; multimodality; neural; neural circuit; neurotransmission; new technology; non rapid eye movement; nonhuman primate; noradrenergic; novel therapeutic intervention; novel therapeutics; operation; optogenetics; prevent; rapid eye movement; sleep behavior; sleep regulation; wireless; wireless communication; wireless electronic

PROJECT SUMMARY Sleep plays a critical role in a vast array of physiological and pathophysiological processes, including executive brain functions, immune and metabolic functions, and neurodegenerative diseases. An improved understanding of sleep mechanisms is important to developing new treatment strategies. Sleep circuits can be manipulated with numerous techniques to infer causal relationships to physiology and behavior. Effects of these manipulations are generally sleep stage or brain state dependent. Thus, closed-loop interrogation provides a powerful paradigm, whereby a temporally precise manipulation (optogenetic, electrical, or sensory stimulation) is delivered in a brain-state dependent manner. This paradigm has been used successfully in mice and humans tethered to data acquisition, state classification, and stimulation hardware. However, tethering can adversely affect natural sleep behavior and prevents use in larger animal models. Here, we propose to develop a fully integrated, wireless, sleep modulation system-on-chip (SoC) with the capability to deliver state-dependent, temporally-precise optical, electrical, and auditory stimulation. In Aims 1 and 2, Co-PI Dr. Liu will iteratively develop an ultra-low-power SoC for polysomnography (PSG) signal acquisition and multi-modal closed-loop stimulation. The final SoC will have five modules: (1) a low-noise, high-precision PSG acquisition module, (2) a programmable mixed-signal data compression module for energy efficiency, (3) a low-power ultra-wideband wireless transmitter, (4) a machine learning-based sleep stage classification module, and (5) a fully programmable multi-modal stimulator. Full integration of the system will result in a small (2 cm3), light (2 g) battery-powered device able to operate continuously for over 10 h on a single charge. In Aim 3, running concurrently with the first two aims, Co-PI Dr. Richardson will validate performance of the SoC with sleep studies in both small (rats) and large (macaques) animal models. Interleaved recordings from the wireless SoC and a tethered commercial system will assess fidelity of compressed PSG acquisition and the impact of tethering on sleep architecture. Real-time 2-stage and all-stage classifiers will be compared to offline ground truth labels. Finally, in-phase closed-loop auditory stimulation will be used to enhance slow wave activity. Our team is uniquely qualified for this proposal since we have extensive experience developing the key modules in the proposed SoC and using wireless electronics for free behavior electrophysiological experiments in both animal models. Once developed, two industry partners, CMC Microsystems and Open Ephys, Inc., will facilitate distribution of the SoC to the worldwide community. The closed-loop SoC will enable unprecedented hypothesis- driven research on sleep-stage specific neural circuits and interventions in models spanning from mice to monkeys, thereby accelerating the mechanistic understanding of sleep and treatment of sleep disorders.

项目概要 睡眠在一系列生理和病理生理过程中发挥着至关重要的作用，包括执行 脑功能、免疫和代谢功能以及神经退行性疾病。更好的理解 睡眠机制的研究对于制定新的治疗策略非常重要。睡眠电路可以被操纵 使用多种技术来推断生理和行为的因果关系。这些的影响 操作通常取决于睡眠阶段或大脑状态。因此，闭环询问提供了 强大的范例，通过时间精确的操纵（光遗传学、电学或感觉刺激） 以依赖于大脑状态的方式传递。该范例已成功应用于小鼠和人类 与数据采集、状态分类和刺激硬件相关。然而，网络共享可能会产生不利影响 影响自然睡眠行为并妨碍在大型动物模型中使用。在此，我们建议开发一个完整的 集成、无线、睡眠调制片上系统 (SoC)，能够提供状态相关、 时间精确的光学、电学和听觉刺激。在目标 1 和 2 中，联合 PI 刘博士将迭代 开发用于多导睡眠图 (PSG) 信号采集和多模态闭环的超低功耗 SoC 刺激。最终的 SoC 将具有五个模块：(1) 低噪声、高精度 PSG 采集模块，(2) 用于提高能效的可编程混合信号数据压缩模块，(3) 低功耗超宽带 无线发射器，（4）基于机器学习的睡眠阶段分类模块，以及（5）完全 可编程多模式刺激器。系统的完全集成将导致体积小（2 cm3）、重量轻（2 g） 电池供电的设备一次充电可连续运行 10 小时以上。在目标 3 中，跑步 在实现前两个目标的同时，联合 PI Richardson 博士将通过睡眠研究验证 SoC 的性能 在小型（大鼠）和大型（猕猴）动物模型中。来自无线 SoC 的交错录音和 系留商业系统将评估压缩 PSG 采集的保真度以及系留对 睡眠架构。实时两阶段和全阶段分类器将与离线地面实况标签进行比较。 最后，同相闭环听觉刺激将用于增强慢波活动。我们的团队是 由于我们在开发关键模块方面拥有丰富的经验，因此我们具有独特的资格来胜任该提案 提出的 SoC 并使用无线电子技术在两种动物中进行自由行为电生理实验 模型。一旦开发完成，两个行业合作伙伴 CMC Microsystems 和 Open Ephys, Inc. 将促进 向全球社区分发 SoC。闭环 SoC 将实现前所未有的假设—— 推动了对睡眠阶段特定神经回路的研究以及从小鼠到模型的干预 猴子，从而加速对睡眠机制的理解和睡眠障碍的治疗。

项目成果

Design of a Sleep Modulation System with FPGA-Accelerated Deep Learning for Closed-loop Stage-Specific In-Phase Auditory Stimulation.

采用 FPGA 加速深度学习的睡眠调制系统设计，用于闭环特定阶段同相听觉刺激。

• DOI: 10.1109/iscas46773.2023.10181356
• 发表时间: 2023
• 期刊: IEEE International Symposium on Circuits and Systems proceedings. IEEE International Symposium on Circuits and Systems
• 作者: Sun,Mingzhe;Zhou,Aaron;Yang,Naize;Xu,Yaqian;Hou,Yuhan;Richardson,AndrewG;Liu,Xilin
• 通讯作者: Liu,Xilin