Sabnis Gautam, Hession Leinani, Mahoney J Matthew, Mobley Arie, Santos Marina, Kumar Vivek
The Jackson Laboratory, Bar Harbor, ME USA.
School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, MA USA.
bioRxiv. 2024 May 30:2024.05.29.596520. doi: 10.1101/2024.05.29.596520.
Seizures are caused by abnormally synchronous brain activity that can result in changes in muscle tone, such as twitching, stiffness, limpness, or rhythmic jerking. These behavioral manifestations are clear on visual inspection and the most widely used seizure scoring systems in preclinical models, such as the Racine scale in rodents, use these behavioral patterns in semiquantitative seizure intensity scores. However, visual inspection is time-consuming, low-throughput, and partially subjective, and there is a need for rigorously quantitative approaches that are scalable. In this study, we used supervised machine learning approaches to develop automated classifiers to predict seizure severity directly from noninvasive video data. Using the PTZ-induced seizure model in mice, we trained video-only classifiers to predict ictal events, combined these events to predict an univariate seizure intensity for a recording session, as well as time-varying seizure intensity scores. Our results show, for the first time, that seizure events and overall intensity can be rigorously quantified directly from overhead video of mice in a standard open field using supervised approaches. These results enable high-throughput, noninvasive, and standardized seizure scoring for downstream applications such as neurogenetics and therapeutic discovery.
癫痫发作是由异常同步的大脑活动引起的,这种活动会导致肌肉张力的变化,如抽搐、僵硬、松弛或有节奏的抽搐。这些行为表现通过视觉检查很明显,并且临床前模型中最广泛使用的癫痫发作评分系统,如啮齿动物的拉辛量表,在半定量癫痫发作强度评分中使用这些行为模式。然而,视觉检查耗时、低通量且部分主观,因此需要可扩展的严格定量方法。在本研究中,我们使用监督机器学习方法开发自动分类器,以直接从无创视频数据预测癫痫发作严重程度。利用小鼠的戊四氮诱导癫痫模型,我们训练仅基于视频的分类器来预测发作期事件,将这些事件结合起来预测一次记录会话的单变量癫痫发作强度以及随时间变化的癫痫发作强度评分。我们的结果首次表明,使用监督方法可以直接从标准开放场地中小鼠的头顶视频对癫痫发作事件和总体强度进行严格量化。这些结果为神经遗传学和治疗发现等下游应用实现了高通量、无创和标准化的癫痫发作评分。