Adapting Biomarker Assays for Individuals with Autism and Intellectual Disability

针对自闭症和智力障碍患者调整生物标志物检测

• 批准号: 9917304
• 负责人: James Charles McPartland
• 金额: $ 25.13万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-23 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9917304
• 关键词: Age; Attenuated; Behavior; Behavior Therapy; Behavioral; Biological Assay; Biological Markers; Brain; Caregivers; Child; Clinical; Clinical Trials; Collection; Computer Vision Systems; Data; Data Quality; Development; Electroencephalogram; Environment; Event-Related Potentials; Experimental Designs; Eye; Face; Family; Feedback; Goals; Human; Individual; Instruction; Intellectual functioning disability; Intervention; Measures; Methods; Morphologic artifacts; Motion; Neurosciences; Participant; Pattern; Pharmacology; Population; Publishing; Research; Sampling; Scalp structure; Selection for Treatments; Severities; Stimulus; Subgroup; Symptoms; Technology; Testing; Time; United States Food and Drug Administration; Visual attention; Work; autism diagnostic observation schedule; autism spectrum disorder; autistic children; biomarker development; candidate marker; experimental study; gaze; indexing; innovation; middle childhood; minimally invasive; novel; novel strategies; programs; relating to nervous system; response; social; symptomatology; tool; treatment response

Project Summary/Abstract The field of autism spectrum disorder (ASD) research lacks objective, sensitive quantifications of symptomatology with sufficient evidence to justify use as biomarkers in clinical trials. In the current proposal we investigate two promising markers, neural response to faces, measured by electroencephalogram (EEG), and visual attention to faces, measured by eye-tracking (ET). Published work and our preliminary data indicate that these measures: reflect clinically meaningful differences in the core symptoms of ASD, both by discriminating groups with ASD from those with typical development (TD) and by correlating with symptomatology in individuals with ASD; have strong test-retest reliability; demonstrate sensitivity to change in clinical status, both in the context of pharmacological and behavioral intervention; are collected by objective, automated tools not vulnerable to issues associated with inter-rater or inter-operator reliability; are minimally invasive and highly tolerable and therefore applicable across a wide range of ages and functional levels, with acceptable burden for participants and families; are collected using economical and accessible technologies that are scalable for large multisite studies with potential utility in the near term. Despite the promise of these biomarkers, their appropriateness in individuals with ASD and intellectual disability (ASD+ID) is poorly understood. In this application, we propose a novel integration of technologies and an innovative experimental approach to investigate these promising biomarkers in this critically understudied population. We leverage two complementary lines of research developed by the PIs: Dr. McPartland's Autism Biomarkers Consortium for Clinical Trials (ABC-CT), a multisite study collecting large samples of highly reliable EEG and ET data in children with ASD, and Dr. Naples' suite of gaze- and behaviorally-contingent technologies permitting concurrent collection of ET and EEG data in individuals with severe ID. The proposed work will incorporate robust ABC-CT experiments into an innovative experimental approach to study 30 6-11 year old children with ASD+ID and a matched sample of 30 individuals with ID without ASD. We test the hypotheses that individuals with ASD+ID will display longer latency of the N170 event-related potential (ERP) to human faces and reduced proportion of looking time to human faces in static social scenes relative to individuals with ID without ASD and that face N170 and visual attention to faces will correlate with clinician and caregiver ratings of social- communicative function. This innovative project uses a suite of contingent technologies to acclimate participants to the testing environment and apparatus, to attenuate motion, to permit real time feedback on data quality to prioritize stimulus delivery, and to support post-processing of motion artifact using computer vision derived motion estimates. By adapting robust markers for administration to individuals with ASD and ID, this application holds promise for development of biomarkers viable in an understudied but critically important segment of the autism spectrum.

项目总结/摘要 自闭症谱系障碍（ASD）研究领域缺乏客观，敏感的量化， 有充分证据证明在临床试验中用作生物标志物的合理性。在目前的提案中，我们 研究两个有希望的标记，对面部的神经反应，通过脑电图（EEG）测量， 通过眼动追踪（ET）测量的对面部的视觉注意力。已发表的工作和我们的初步数据表明， 这些指标：反映ASD核心症状的临床有意义的差异， ASD组与典型发育（TD）组之间的差异， ASD患者;有很强的重测信度;表现出对临床状态变化的敏感性， 在药理学和行为干预的背景下;通过客观的自动化工具收集， 易受评估者间或操作者间可靠性相关问题的影响;微创且高度 可耐受，因此适用于广泛的年龄和功能水平，负担可接受 为参与者和家庭;使用经济和可访问的技术收集，可扩展， 在短期内具有潜在效用的大型多中心研究。尽管这些生物标志物的承诺，他们的 ASD和智力残疾（ASD+ID）个体的适当性知之甚少。在这 应用，我们提出了一种新的技术集成和创新的实验方法， 在这个研究严重不足的人群中研究这些有希望的生物标志物。我们利用两个 由PI开发的补充研究线：McPartland博士的自闭症生物标志物联盟， 临床试验（ABC-CT），一项多中心研究，收集了大量高度可靠的EEG和ET数据， 患有自闭症的儿童，以及那不勒斯博士的一套凝视和行为相关技术， 同时收集ET和EEG数据的个人与严重的ID。拟议的工作将包括 一个强大的ABC-CT实验到一个创新的实验方法，研究30 6-11岁的儿童与 ASD+ID和30名ID无ASD的个体的匹配样本。我们检验了个体 与ASD+ID将显示更长的潜伏期的N170事件相关电位（ERP）的人脸和减少 在静态社交场景中，相对于没有ASD的ID个体， 面部N170和对面部的视觉注意力将与临床医生和护理人员的社会- 交际功能这个创新项目使用一套应急技术来适应 测试环境和设备的参与者，以衰减运动，以允许对运动的真实的时间反馈， 数据质量，以优先考虑刺激输送，并支持使用计算机对运动伪影进行后处理 视觉导出的运动估计。通过使稳健的标记物适应于施用于患有ASD和ID的个体， 这一应用为开发生物标志物提供了希望，这些生物标志物在研究不足但至关重要的领域中是可行的。 自闭症谱系的一部分。