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.

抽象的 自闭症谱系障碍（ASD）会影响44个儿童中的一个。 1早期诊断对于优化至关重要 结果，但通常要等到4岁才能诊断出儿童。2与早期行为迹象一致， 早期的神经标记物可以识别出患有ASD的风险的幼儿，以帮助早期诊断并针对目标 干预措施。神经影像学研究主要检查了高幼儿的结构性脑异常 发展ASD3的风险。越来越多的工作为功能性大脑网络连接提供了证据 ASD年龄较大的儿童（7-12岁）的改变。4而创新的动态功能磁 共振成像（fMRI）方法揭示了候选功能障碍的候选脑网络。 迄今为止，ASD的年龄较大儿童的疾病和症状严重程度迄今已评估了这种关系 与ASD的幼儿中的大脑网络动力学和行为结果之间。限制和重复 尤其了解行为（RRB），ASD的核心症状，9。该项目的目的是确定 ASD的早期功能性脑生物标志物和脑行为与RRB结局的关系 临床和通常发育（TD）组。这项研究将利用UCSD先前收集的数据集 ACE中心完成了幼儿（12-36个月，n = 231），他们被确定为TD或处于危险中 使用早期筛选形式（交流和符号行为量表）发育残疾 发展概况； csbs-dp）.10少数幼儿后来被诊断为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，该数据集为检查ASD的早期脑生物标志物提供了独特的机会 如研究领域标准（RDOC）方法所设想的诊断类别的RRB。1111 仅早期行为指标并不总是清楚地表明哪些孩子将继续发展ASD。12 这项研究的结果可能导致发展可靠的生物标志物，以识别有ASD风险的儿童 音乐会与疾病的明显行为迹象。 ASD和RRB的神经生物标志物反过 以及更有效的诊断和治疗方法。这项工作以申请人以前的研究经验为基础 在UCSD ACE中心收集来自幼儿的神经影像学数据。13先前检查了 ASD年龄较大儿童（8-12 YO）的RRB症状的动态脑生物标志物，7,14-16审查了大脑 具有ASD，3分析的大型寿命神经成像数据集的幼儿中的生物标志物文献（n = 601），并获得了 统计和临床神经科学的基础。通过正式的课程和个人会议， 申请人计划从事四个主要培训领域：（1）评估大脑动态的尖端分析 使用功能性神经成像数据，（2）用于建模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，以及（4）职业发展。