ConProject-001

ConProject-001

• 批准号: 10001020
• 负责人: CONNIE L. KASARI
• 金额: $ 28.9万
• 依托单位: BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10001020
• 关键词: 3-Dimensional; Address; Age; Behavior; Behavior Therapy; Behavioral; Biological Markers; Boston; Brain; California; Child; Clinical; Clinical Management; Clinical Research; Collection; Communication; Communication impairment; Communities; DNA; Development; Electrophysiology (science); Enrollment; Etiology; Face; Family; Future; Genetic; Genetic Load; Genetic Research; Genetic Risk; Genetic Variation; Genetic study; Genomics; Goals; Heterogeneity; Impairment; Institution; Intervention; Intervention Studies; Language; Language Development; Language Disorders; Lead; Link; Los Angeles; Measures; Methods; Minority; Molecular Target; Motion; Motor; Neurocognitive Deficit; Neurophysiology - biologic function; Neurosciences; Neurosciences Research; Oral Characters; Outcome; Pathway interactions; Phenotype; Population Heterogeneity; Randomized; Randomized Controlled Trials; Research; Risk; Saliva; Sampling; Schools; Science; Severities; Speech; Subgroup; Technology; Time; Universities; Work; autism spectrum disorder; autistic children; base; behavioral phenotyping; clinical practice; control trial; data management; endophenotype; evidence base; follow-up; genetic predictors; genetic risk factor; innovation; joint attention; language impairment; language outcome; medical schools; motor impairment; multidisciplinary; neglect; neural correlate; neuromechanism; novel; novel therapeutic intervention; oral motor; predictive marker; rare variant; recruit; relating to nervous system; response; social communication; sound; tool; treatment response

PROJECT SUMMARY/ABSTRACT A significant number of children with ASD remain minimally verbal even after receiving quality interventions. Recent studies have highlighted the heterogeneity of this group confirming that no single mechanism can explain the underlying causes of their severe communication deficits. At the same time, innovative targeted behavioral interventions can lead to improvements in speech and social communication in some minimally verbal children. The goals of this Center, located at Boston University and University of California Los Angeles, are to build on our earlier work addressing a central theme: Which young minimally verbal children with ASD make gains acquiring language during the early school years and how can we facilitate such progress? We approach these questions from a multidisciplinary perspective, employing tools, methods, and approaches drawn from communication disorders, speech and motor science, developmental neuroscience, genetics and interventions research. The four interconnected projects address the following aims. Aim 1: To identify motor and neural mechanisms underlying the profound spoken language impairments that define minimally verbal children with autism. In two projects on the same group of young minimally verbal children we plan to characterize oral and general motor functioning using state-of- the-art technologies, and electrophysiology to probe neural functioning (Project 1, 2). Aim 2: To advance our understanding of how to optimize the language outcomes of young minimally verbal children with ASD. We address this by carrying out a randomized controlled trial of a behavioral intervention that combines social communication and oromotor targets (Project 3) and by following the children studied in Aim 1 for two years to explore how changes in motor and neural functioning may predict diverse language pathways (Projects 1, 2). Aim 3: To investigate genetic risk factors associated with minimally verbal ASD, including both common and rare variants (Project 4). We plan to leverage the children enrolled in all the projects to explore the relationship between the quantitative load for common polygenic risk for ASD and language, motor, and neural phenotypes as well as genetic predictors of response to treatment and more optimal developmental outcomes (all Projects). The projects are united and served by an Administrative Core (A) and a Clinical and Data Management Scientific Core (B) that will carry out comprehensive assessments using available and novel measures to capture the heterogeneous phenotypes of minimally verbal children with ASD. Together, the research conducted in our Center will significantly advance our understanding of the profound communication deficits at this neglected end of the autism spectrum, develop behavioral and neural biomarkers that predict different developmental pathways for language, and may highlight potential molecular targets for future novel therapeutic interventions.

项目摘要/摘要 即使在接受了高质量的干预后，相当数量的自闭症儿童仍然保持着最低限度的语言能力。 最近的研究强调了这一群体的异质性，证实了没有单一的机制可以 解释他们严重沟通障碍的根本原因。同时，有针对性地创新 行为干预可以在一定程度上改善言语和社交交流 会说话的孩子。位于波士顿大学和加州大学洛杉矶分校的这个中心的目标 洛杉矶，将在我们早期工作的基础上解决一个中心主题：哪个年轻人说话最少 患有自闭症的儿童在早期的学习中获得了语言，我们如何才能 促进这样的进步？我们从多学科的角度来处理这些问题，采用 从沟通障碍、言语和运动学中提取的工具、方法和途径， 发展神经科学、遗传学和干预研究。四个相互关联的项目解决了 目标有以下几点。目标1：确定深奥的言语背后的运动和神经机制 定义自闭症儿童语言能力最弱的语言障碍。在同一组的两个项目中 对于言语能力较弱的儿童，我们计划使用状态来表征其口腔和一般运动功能。 最先进的技术和电生理学来探测神经功能(项目1，2)。目标2：奋发有为 我们对如何优化幼儿最低限度言语能力的理解 ASD.我们通过开展一项行为干预的随机对照试验来解决这一问题 社会交流和运动目标(项目3)，并通过跟踪目标1中研究的儿童来实现 多年来探索运动和神经功能的变化如何预测不同的语言路径 (项目1、2)。目的3：探讨与少言性自闭症相关的遗传危险因素。 包括常见和罕见的变种(项目4)。我们计划利用参加所有 探索ASD常见多基因风险的定量负荷与 语言、运动和神经表型以及治疗反应的遗传预测因子等 最佳发展成果(所有项目)。这些项目是统一的，并由一个管理核心提供服务 (A)和将开展全面评估的临床和数据管理科学核心(B) 使用可用和新颖的方法捕捉言语少的儿童的异质性表型 患有自闭症。总之，在我们中心进行的研究将极大地促进我们对 在自闭症谱系中这一被忽视的一端的严重沟通缺陷，会发展成行为和 神经生物标记物预测语言的不同发展路径，并可能突出潜力 未来新型治疗干预的分子靶点。