CARE4Kids: Autonomic Biomarker Core

CARE4Kids：自主生物标记核心

• 批准号: 10203600
• 负责人: ROBERT F ASARNOW
• 金额: $ 17.68万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-08 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10203600
• 关键词: Acute; Address; Adolescent; Age; Autonomic Dysfunction; Autonomic nervous system; Autonomic nervous system disorders; Biological Factors; Biological Markers; Blood Pressure; Brain; Brain Concussion; Brain Injuries; Brain imaging; Breathing; Cardiovascular system; Chronic; Clinical; Cognitive; Congenital neurologic anomalies; Data; Data Analyses; Development; Educational Status; Equipment; Functional disorder; Gender; Goals; Heart Rate; Hour; Link; Literature; Longitudinal Studies; Manuals; Measures; Methodology; Nervous System Physiology; Neuraxis; Neurobiology; Patients; Phase; Physiological; Pilot Projects; Post-Concussion Syndrome; Postural adjustments; Prognosis; Protocols documentation; Quality Control; Recovery; Research Assistant; Research Project Grants; Research Training; Rest; Sample Size; Signs and Symptoms; Site; Standardization; Structure; Symptoms; Testing; Time; Training; Validation; Variant; analytical method; axon injury; blood-based biomarker; clinical decision-making; cohort; concussive symptom; design; endophenotype; heart rate variability; imaging biomarker; imaging modality; innovation; molecular marker; neuroinflammation; neuropsychiatric disorder; predictive marker; psychological stressor; respiratory; response; systematic review

PROJECT SUMMARY/ABSTRACT – Autonomic Biomarker Core While many symptoms and signs of autonomic nervous system (ANS) disorder are found in patients with persistent post-concussive symptoms (PPCS), ANS function in concussion has been extraordinarily understudied, particularly in adolescents. Despite the limited number of studies, there is clear evidence of ANS dysfunction sub-acutely and chronically following concussion. In a recent systematic review, 33/36 studies identified ANS anomalies in concussed athletes and non-athletes. The most consistent findings are lower parasympathetic activity during rest and activities that normally enhance parasympathetic response, such as deep breathing, as well as activities that normally enhance sympathetic response, such as orthostatic challenge. There are, however, major limitations in existing studies including very few studies of adolescents, small to modest sample sizes (~20 patients), and limited sets of ANS measures or autonomic challenges used in any one study. Because of these methodological limitations, prior studies do not provide clear guidance as to the best set of measures and testing conditions to assess ANS function in adolescents with PPCS. We will develop a comprehensive, scalable assessment of ANS function in adolescents. Among the many innovative features of this panel are: 1) both cardiovascular and pupillary measures of sympathetic and parasympathetic function, and 2) a standardized set of brief physiological challenges to assess both sympathetic and parasympathetic activity. We use rest, recovery, and deep breathing protocols to maximize sensitivity for detecting parasympathetic dysfunction. We use an orthostatic challenge and a psychological stressor to maximize sensitivity for detecting sympathetic dysfunction. Heart rate variability as well as heart rate, respiratory rate, and blood pressure will be recorded concurrently during these activities. We use pupillometry as a complementary non-cardiac assessment of autonomic dysfunction. We will also 3) develop norms by age and gender for all of the measures in the panel that can be incorporated into clinical decision-making. The broad range of ANS measures and testing conditions used here will identify the measures and testing conditions that best predict the persistence of concussive symptoms. This panel of measures will be used to characterize one or more ANS endophenotypes linked to clusters of PPCS symptoms. The panel of ANS measures developed here will help elucidate the pathobiologies underlying PPCS by examining the link between ANS and central nervous system markers and blood-based markers of axonal injury and neuroinflammation.

项目总结/摘要-自主生物标志物核心 虽然许多自主神经系统（ANS）紊乱的症状和体征在患有 持续性脑震荡后症状（PPCS），脑震荡中的ANS功能异常， 尤其是在青少年中。尽管研究数量有限，但有明确的证据表明， 脑震荡后亚急性和慢性ANS功能障碍。在最近的一项系统综述中，33/36项研究 在脑震荡的运动员和非运动员中发现了ANS异常。最一致的发现是低 休息时的副交感神经活动和通常增强副交感神经反应的活动，例如 深呼吸，以及通常增强交感神经反应的活动，如直立挑战。 然而，现有的研究有很大的局限性，包括很少的青少年研究，小到 适度的样本量（约20名患者），以及在任何研究中使用的有限的ANS测量或自主神经挑战集。 一项研究。由于这些方法上的限制，先前的研究没有提供明确的指导， 评估PPCS青少年ANS功能的最佳措施和测试条件。我们将开发 对青少年ANS功能进行全面、可扩展的评估。在众多创新功能中， 该组是：1）交感神经和副交感神经功能的心血管和瞳孔测量，以及 2)一套标准化的简短生理挑战，以评估交感神经和副交感神经活动。 我们使用休息，恢复和深呼吸协议，以最大限度地提高检测副交感神经的灵敏度 功能障碍我们使用直立挑战和心理压力源来最大化检测的灵敏度 交感神经功能障碍心率变异性以及心率、呼吸频率和血压将被 在这些活动中同时记录。我们使用瞳孔测量作为补充非心脏评估 自主神经功能紊乱我们还将为小组中的所有指标制定按年龄和性别划分的标准 可以被纳入临床决策。广泛的ANS测量和测试条件 这里使用的是确定最能预测脑震荡持续性的措施和测试条件， 症状这一组测量将用于表征一个或多个ANS内表型， PPCS症状群。这里开发的ANS测量面板将有助于阐明病理生物学 通过检查ANS和中枢神经系统标志物之间的联系， 轴突损伤和神经炎症的标志物。