Brain-based biomarkers of restricted and repetitive behaviors in toddlers at risk for autism

有自闭症风险的幼儿的限制性和重复性行为的基于大脑的生物标志物

• 批准号: 10751977
• 负责人: Lauren Kupis
• 金额: $ 3.97万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-10 至 2025-08-09
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10751977
• 关键词: 12 year old; 4 year old; Affect; Area; Autism Diagnosis; Behavior; Behavioral; Biological; Biological Markers; Brain; Caregivers; Categories; Child; Clinical; Cognition; Cognitive; Communication; Data; Data Analyses; Data Set; Development; Developmental Delay Disorders; Developmental Disabilities; Diagnosis; Diagnostic; Dimensions; Disease; Distress; Early Diagnosis; Early identification; Family; Foundations; Functional Magnetic Resonance Imaging; Goals; Heterogeneity; Impairment; Individual; Intervention; Language Delays; Lateral; Learning; Life; Literature; Longevity; Machine Learning; Maps; Measures; Medial; Methods; Modeling; Neurosciences; Outcome; Reporting; Research; Research Domain Criteria; Research Methodology; Rest; Risk; Sampling; Seminal; Severities; Sleep; Social Adjustment; Social Development; Symptoms; Techniques; Testing; Time; Toddler; Training; Work; autism diagnostic observation schedule; autism spectrum disorder; autistic children; behavior prediction; behavioral outcome; brain abnormalities; brain based; brain behavior; career; career development; cognitive development; critical period; daily functioning; early screening; experience; flexibility; high risk; imaging modality; improved; innovation; meetings; network dysfunction; neural; neural correlate; neuroimaging; novel; prospective; psychologic; repetitive behavior; skills; social communication; statistics; targeted treatment

Abstract Autism spectrum disorder (ASD) affects one in 44 children. 1 Early diagnosis is critical for optimizing outcomes, yet children are not typically diagnosed until 4 years of age.2 In concert with early behavioral signs, early neural markers could identify toddlers at risk of developing ASD to aid earlier diagnosis and targeted interventions. Neuroimaging studies have primarily examined structural brain abnormalities in toddlers at high risk of developing ASD3. A growing body of work provides evidence for functional brain network connectivity alterations in older children with ASD (7-12 years of age).4 While innovative dynamic functional magnetic resonance imaging (fMRI) methods reveal candidate brain networks of dysfunction underlying the heterogeneity of the disorder and symptom severity in older children with ASD,567,8no study to date has evaluated the relationship between brain network dynamics and behavioral outcomes in toddlers with ASD. Restricted and repetitive behaviors (RRBs), core symptoms of ASD,9 are particularly understudied. The goal of this project is to identify early functional brain biomarkers of ASD and brain-behavior relationships with RRB outcomes across mixed clinical and typically developing (TD) groups. This study will utilize a dataset previously collected by the UCSD ACE Center comprised of toddlers (12-36 months, n = 231) who were identified as either TD or at-risk for a developmental disability using an early screening form (Communication and Symbolic Behavior Scales Developmental Profile; CSBS-DP).10Some toddlers were later diagnosed with ASD (n = 89), TD (n = 70), other diagnosis (n = 72; Language Delay, Developmental Delay, and Autism Features). Since the sample includes multiple diagnostic groups, this dataset offers a unique opportunity to examine early brain biomarkers for ASD and RRBs across diagnostic categories, as envisioned by the Research Domain Criteria (RDoC) approach.11 Early behavioral indicators alone do not always clearly indicate which children will go onto to develop ASD.12 The results from this study may lead to the development of reliable biomarkers to identify children at risk for ASD in concert with overt behavioral signs of the disorder. Neural biomarkers of ASD and RRBs will in turn lead to earlier and more efficient diagnosis and treatments. This work builds upon the applicant’s previous research experience at the UCSD ACE Center collecting neuroimaging data from toddlers.13 The applicant has previously examined dynamic brain biomarkers of RRB symptoms in older children with ASD (8-12 yo),7,14–16 reviewed the brain biomarker literature in toddlers with ASD,3analyzed large lifespan neuroimaging datasets (n = 601), and gained a foundation in statistics and clinical neuroscience. Through formal coursework and individual meetings, the applicant plans to engage in four major areas of training: (1) cutting-edge analyses to assess brain dynamics using functional neuroimaging data, (2) sophisticated statistical approaches for modelling longitudinal data, (3) considerations for conducting research with young children at risk for autism, and (4) career development.

摘要 每44名儿童中就有一名患有自闭症谱系障碍（ASD）。 1早期诊断对优化至关重要 结果，但儿童通常直到4岁才被诊断出来。2与早期行为体征一致， 早期神经标记物可以识别有发展ASD风险的幼儿，以帮助早期诊断和靶向治疗。 干预措施。神经影像学研究主要检查了高血压幼儿的大脑结构异常。 发展ASD的风险3。越来越多的工作为功能性大脑网络连接提供了证据 虽然创新的动态功能性磁共振成像技术在ASD患儿（7-12岁）中的应用 核磁共振成像（fMRI）方法揭示了异质性背后的功能障碍的候选脑网络 年龄较大的ASD儿童的障碍和症状严重程度，567，8迄今为止没有研究评估这种关系， 自闭症幼儿的大脑网络动力学和行为结果之间的联系。限制和重复 行为（RRB），ASD的核心症状，9特别是研究不足。本项目的目标是确定 ASD的早期功能性脑生物标志物和脑行为与RRB结果的关系， 临床和典型发育（TD）组。这项研究将利用UCSD以前收集的数据集 ACE中心由幼儿（12-36个月，n = 231）组成，这些幼儿被确定为TD或存在以下风险： 使用早期筛查表（沟通和象征行为量表）的发育障碍 发育概况; CSBS-DP）。10一些幼儿后来被诊断为ASD（n = 89），TD（n = 70），其他 诊断（n = 72;语言延迟，发育延迟和自闭症特征）。由于样本包括 多个诊断组，该数据集提供了一个独特的机会，检查ASD的早期大脑生物标志物 和RRB跨诊断类别，正如研究领域标准（RDoC）方法所设想的那样。 早期行为指标本身并不总是清楚地表明哪些孩子会发展为ASD。 这项研究的结果可能会导致可靠的生物标志物的发展，以确定儿童在ASD的风险， 与这种疾病的明显行为迹象相一致。ASD和RRB的神经生物标志物反过来会导致更早的 更有效的诊断和治疗。这项工作建立在申请人以前的研究经验之上 在UCSD ACE中心收集幼儿的神经成像数据。13申请人先前已经检查了 对年龄较大的ASD儿童（8-12岁）RRB症状的动态脑生物标志物进行了回顾，7，14 -16 在ASD幼儿的生物标志物文献中，3分析了大型寿命神经成像数据集（n = 601），并获得了 统计学和临床神经科学的基础。通过正式的课程和个别会议， 申请人计划从事四个主要领域的培训：（1）尖端分析，以评估大脑动力学 使用功能性神经影像学数据，（2）模拟纵向数据的复杂统计方法，（3） 对有自闭症风险的幼儿进行研究的考虑;（4）职业发展。