CounterAct Administrative Supplement to NS114020 Automated Phenotyping in Epilepsy

CounterAct NS114020 癫痫自动表型分析行政补充

• 批准号: 10227611
• 负责人: Sandeep R Datta
• 金额: $ 12.38万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-10-01 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10227611
• 关键词: 3-Dimensional; Acute; Address; Administrative Supplement; Animal Behavior; Animals; Antiepileptic Agents; Artificial Intelligence; Behavior; Behavioral; Cannabidiol; Chronic; Cognitive; Communities; Complex; Data; Detection; Development; Drug Screening; Electroencephalography; Epilepsy; Exposure to; Goals; Human; Intoxication; Isoflurophate; Long-Term Effects; Longitudinal Studies; Methods; Modeling; Monitor; Motion; Mus; Neurologic Effect; Observer Variation; Pesticides; Pharmaceutical Preparations; Phenotype; Play; Probability; Public Health; Reproducibility; Research; Rest; Seizures; Status Epilepticus; Stereotyping; Structure; Techniques; Technology; Testing; Three-dimensional analysis; Time; acquired epilepsy; automated algorithm; comorbidity; improved; innovation; medical countermeasure; nerve agent; neuroinflammation; neuronal circuitry; novel therapeutics; parent grant; pre-clinical research; screening; tool; valproate

Acute intoxication with organophosphorus (OP) pesticides is a significant public health concern and long-term neurological effects are not well understood. A major obstacle to progress towards reproducible, rigorous preclinical research in the long-term effects of OP- induced status epilepticus is that current experimental approaches often require prohibitively time and labor-intensive 24/7 video-EEG monitoring and inherently subjective scoring of seizures by human observers (like the widely used Racine scale). While algorithms for automated seizure detection in EEG are improving, the critically important behavioral manifestations of acquired epilepsy and assessment of its cognitive comorbidities remain poorly quantified. Our parent grant focuses on developing an objective, high-throughput technique to characterize epileptic phenotypes using a new method called motion sequencing (MoSeq) and apply it to automated anti-epileptic drugs (AED) screening. The central idea of MoSeq rests on the discovery that complex animal behaviors are structured in stereotyped modules (“syllables”) at sub-second timescales that are arranged according to specific rules (“grammar”) that can be detected without observer bias by artificial intelligence (AI)-assisted 3D video analysis. In this administrative supplement project, we propose to employ and refine MoSeq to address key challenges in research into the development of new medical countermeasures (MCM) against nerve agents and OP pesticides. This includes testing if it is possible to objectively study the long-term effects of OP intoxication and evaluate MCMs at scale by determine epilepsy-specific behavioral modules and associated transition probabilities in mice after acute OP exposure. In addition, given that neuroinflammation is likely to play a key role in OP-induced persistent neuronal circuit disturbance, we will test if microglial depletion can rescue the OP-induced chronic changes in behavioral syllables and transition probabilities. Together, the aims in this administrative supplement will both benefit from and contribute to our parent grant’s goal to develop a reliable, sharable tool for the research community to study seizures and cognitive comorbidities of epilepsy.

有机磷（OP）农药急性中毒是一个重要的公共卫生问题 关注和长期神经系统影响尚不清楚。 OP-的长期影响可重复、严格的临床前研究取得进展 诱发癫痫持续状态的一个原因是当前的实验方法通常需要过高的 时间和劳动力密集型 24/7 视频脑电图监测和固有的主观评分 人类观察者的癫痫发作（如广泛使用的拉辛量表）。 脑电图的自动癫痫发作检测正在改进，这是至关重要的行为 获得性癫痫的表现及其认知合并症的评估仍然很差 我们的家长资助重点是开发一种客观的、高通量的技术来 使用一种称为运动测序 (MoSeq) 的新方法来表征癫痫表型， 将其应用于自动化抗癫痫药物（AED）筛选 MoSeq 的中心思想在于。 发现复杂的动物行为是由刻板模块（“音节”）构成的 在亚秒级时间尺度上，根据特定规则（“语法”）排列，可以 通过人工智能 (AI) 辅助的 3D 视频分析，可以在没有观察者偏差的情况下进行检测。 行政补充项目，我们建议采用和完善 MoSeq 来解决关键问题 研究开发新的医疗对策（MCM）的挑战 这包括测试是否可以客观地研究神经毒剂和有机磷杀虫剂。 OP 中毒的长期影响，并通过确定癫痫特异性来大规模评估 MCM 急性 OP 暴露后小鼠的行为模块和相关转变概率。 此外，鉴于神经炎症可能在 OP 引起的持续性 神经回路紊乱，我们将测试小胶质细胞耗竭是否可以挽救 OP 引起的神经回路紊乱 行为音节和转换概率的慢性变化共同构成了这一目标。 行政补助将受益于并有助于我们的家长补助金的目标 为研究界开发一个可靠、可共享的工具来研究癫痫和认知 癫痫的合并症。