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) 影响每 44 名儿童中就有 1 名。 1 早期诊断对于优化至关重要 但儿童通常要到 4 岁才会被诊断出来。2 与早期行为迹象相一致， 早期神经标记物可以识别有患自闭症谱系障碍风险的幼儿，以帮助早期诊断和有针对性的治疗 神经影像学研究主要检查了幼儿的大脑结构异常。 越来越多的研究工作为功能性大脑网络连接提供了证据。 患有自闭症谱系障碍 (ASD) 的较大儿童（7-12 岁）的变化。4 创新的动态功能磁 磁共振成像（fMRI）方法揭示了异质性潜在功能障碍的候选大脑网络 年龄较大的 ASD 儿童的疾病与症状严重程度的关系，567,8 迄今为止尚无研究评估这种关系 患有自闭症谱系障碍 (ASD) 的幼儿的大脑网络动态与行为结果之间的关系。 行为 (RRB)，即 ASD 的核心症状，9 的研究尤其不足。该项目的目标是确定。 自闭症谱系障碍 (ASD) 的早期功能性大脑生物标志物以及混合型 RRB 结果的大脑行为关系 临床和典型发育 (TD) 组本研究将利用 UCSD 先前收集的数据集。 ACE 中心由幼儿（12-36 个月，n = 231）组成，他们被确定为 TD 或有患 使用早期筛查表（沟通和象征行为量表）来诊断发育障碍 发育概况；CSBS-DP)。10一些幼儿后来被诊断患有 ASD (n = 89)、TD (n = 70) 和其他 诊断（n = 72；语言发育迟缓、发育迟缓和自闭症特征）。 多个诊断组，该数据集提供了检查 ASD 早期大脑生物标志物的独特机会 和跨诊断类别的 RRB，正如研究领域标准 (RDoC) 方法所设想的那样。 11 仅早期行为指标并不总能清楚地表明哪些儿童将发展为自闭症谱系障碍 (ASD)。12 这项研究的结果可能会导致可靠的生物标志物的开发，以识别患有自闭症谱系障碍（ASD）风险的儿童 与 ASD 和 RRB 的神经生物标志物相一致将反过来导致更早的出现。 这项工作建立在申请人之前的研究经验的基础上。 在加州大学圣地亚哥分校 ACE 中心收集幼儿的神经影像数据。13 申请人之前曾检查过 大龄 ASD 儿童（8-12 岁）RRB 症状的动态大脑生物标志物，7,14-16 回顾了大脑 患有自闭症谱系障碍 (ASD) 幼儿的生物标志物文献，3 分析了大型寿命神经影像数据集 (n = 601)，并获得 通过正式的课程作业和个人会议，奠定了统计和临床神经科学的基础。 申请人计划从事四大领域的培训：（1）评估大脑动力学的前沿分析 使用功能神经影像数据，(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因素，以及（4）职业发展。