Neurosurgery, The University of Colorado Anschutz Medical Campus, Aurora, CO 80045, United States of America.
NeuroTechnology Center, The University of Colorado Anschutz Medical Campus, Aurora, CO 80045, United States of America.
J Neural Eng. 2021 Aug 31;18(4). doi: 10.1088/1741-2552/ac1ed1.
Closed-loop neuromodulation technology is a rapidly expanding category of therapeutics for a broad range of indications. Development of these innovative neurological devices requires high-throughput systems for closed-loop stimulation of model organisms, while monitoring physiological signals and complex, naturalistic behaviors. To address this need, we developed CLARA, a closed-loop automated reaching apparatus.Using breakthroughs in computer vision, CLARA integrates fully-automated, markerless kinematic tracking of multiple features to classify animal behavior and precisely deliver neural stimulation based on behavioral outcomes. CLARA is compatible with advanced neurophysiological tools, enabling the testing of neurostimulation devices and identification of novel neurological biomarkers.The CLARA system tracks unconstrained skilled reach behavior in 3D at 150 Hz without physical markers. The system fully automates trial initiation and pellet delivery and is capable of accurately delivering stimulation in response to trial outcome with short latency. Kinematic data from the CLARA system provided novel insights into the dynamics of reach consistency over the course of learning, suggesting that learning selectively improves reach failures but does not alter the kinematics of successful reaches. Additionally, using the closed-loop capabilities of CLARA, we demonstrate that vagus nerve stimulation (VNS) improves skilled reach performance and increases reach trajectory consistency in healthy animals.The CLARA system is the first mouse behavior apparatus that uses markerless pose tracking to provide real-time closed-loop stimulation in response to the outcome of an unconstrained motor task. Additionally, we demonstrate that the CLARA system was essential for our investigating the role of closed-loop VNS stimulation on motor performance in healthy animals. This approach has high translational relevance for developing neurostimulation technology based on complex human behavior.
闭环神经调节技术是治疗广泛适应症的一类快速发展的疗法。这些创新神经设备的开发需要高通量系统，用于对模式生物进行闭环刺激，同时监测生理信号和复杂的自然行为。为了满足这一需求，我们开发了 CLARA，这是一种闭环自动到达装置。
CLARA 利用计算机视觉的突破，将多个特征的全自动、无标记运动跟踪集成在一起，对动物行为进行分类，并根据行为结果精确地提供神经刺激。CLARA 与先进的神经生理工具兼容，能够测试神经刺激设备并识别新的神经生物学标志物。
CLARA 系统以 150 Hz 的频率在 3D 中无物理标记地跟踪无约束的熟练到达行为。该系统完全自动化启动试验和药丸输送，并能够根据试验结果以短潜伏期准确地输送刺激。CLARA 系统的运动学数据提供了有关学习过程中到达一致性动态的新见解，表明学习选择性地改善了到达失败，但不会改变成功到达的运动学。此外，我们利用 CLARA 的闭环功能，证明迷走神经刺激 (VNS) 可以改善健康动物的熟练到达性能并增加到达轨迹一致性。
CLARA 系统是第一个使用无标记姿势跟踪的鼠标行为装置，可根据不受约束的运动任务的结果提供实时闭环刺激。此外，我们证明 CLARA 系统对于我们研究闭环 VNS 刺激对健康动物运动性能的作用至关重要。这种方法对于基于复杂人类行为开发神经刺激技术具有很高的转化相关性。
