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: 10021720
• 负责人: James Charles McPartland
• 金额: $ 20.94万
• 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 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10021720
• 关键词: Age; Attenuated; Behavior; Behavior Therapy; Behavioral; Biological Assay; Biological Markers; Brain; Caregivers; Child; Clinical; Clinical Trials; Collection; Computer Vision Systems; Data; Development; Electroencephalogram; Environment; Event-Related Potentials; Experimental Designs; 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; data quality; experimental study; gaze; indexing; innovation; middle childhood; minimally invasive; multi-site trial; novel; novel strategies; programs; relating to nervous system; response; social; symptomatology; tool; treatment response; visual tracking

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.

项目摘要/摘要 自闭症谱系障碍(ASD)领域的研究缺乏客观、灵敏的量化 症状学有足够的证据证明在临床试验中用作生物标志物是合理的。在目前的提案中，我们 研究两个有希望的标记物，通过脑电(EEG)测量对面孔的神经反应，以及 对面部的视觉注意力，通过眼球跟踪(ET)测量。已发表的工作和我们的初步数据表明 这些措施：反映ASD核心症状在临床上有意义的差异，两者都通过区分 来自典型发展(TD)的ASD组及其与症状的相关性 患有自闭症的个体；有很强的重测可靠性；对临床状态的变化表现出敏感度 在药理学和行为干预的背景下；由客观的自动化工具收集，而不是 易受评分者间或操作员间可靠性相关问题的影响；具有微创和高度侵入性 可容忍的，因此适用于各种年龄和功能水平，负担可接受 对于参与者和家庭；使用经济且可访问的技术进行收集，这些技术可扩展到 近期具有潜在实用价值的大型多点研究。尽管这些生物标记物前景看好，但他们的 对自闭症和智力残疾(ASD+ID)患者的适当性知之甚少。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来 在这个研究严重不足的人群中研究这些有希望的生物标记物。我们利用两个 由PI开发的互补研究系列：McPartland博士的自闭症生物标记物联盟 临床试验(ABC-CT)是一项多点研究，收集了大量高可靠的脑电和ET数据 患有自闭症的儿童，以及那不勒斯博士的一整套凝视和行为应急技术 同时收集患有严重ID的个体的ET和EEG数据。拟议的工作将包括 稳健的ABC-CT实验成为一种创新的实验方法来研究30名6-11岁的儿童 ASD+ID和30例无ASD的ID的配对样本。我们对假设进行了检验 使用ASD+ID将显示N170事件相关电位(ERP)对人脸的潜伏期更长，并减少 在静态社交场景中看人脸的时间相对于没有ASD的ID个体和 面孔N170和对面孔的视觉注意力将与临床医生和照顾者对社交- 交际功能。这个创新的项目使用了一套应急技术来适应 参与者到测试环境和设备，以衰减运动，以允许实时反馈 数据质量，以确定刺激传递的优先顺序，并支持使用计算机进行运动伪影的后处理 视觉得到了运动估计。通过为患有ASD和ID的个体调整用于给药的健壮标记， 这一应用为生物标记物的开发提供了希望，这种生物标记物在研究不足但至关重要的 自闭症谱系的一部分。