ConProject-001

基本信息

批准号：
10470957
负责人：
CONNIE L. KASARI
金额：
$ 28.87万
依托单位：
BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
依托单位国家：
美国
项目类别：
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/10470957
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 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 Controlled Trials Research Risk Saliva Sampling Schools Science Severities Speech Subgroup Technology Time Universities Work autism community autism spectrum disorder autistic children base behavioral phenotyping clinical practice 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

项目摘要

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.

项目概要/摘要即使在接受高质量的干预措施后，大量患有自闭症谱系障碍的儿童仍然很少使用言语。最近的研究强调了该群体的异质性，证实没有任何单一机制可以解释他们严重沟通缺陷的根本原因。同时，创新针对性行为干预可以在某些方面改善言语和社交沟通言语的孩子。该中心位于波士顿大学和加州大学洛杉矶分校的目标安吉利斯，将以我们早期的工作为基础，解决一个中心主题：哪些年轻人的语言能力最低患有自闭症谱系障碍 (ASD) 的儿童在学前阶段获得了语言学习的进步，我们如何才能促进这样的进展？我们从多学科的角度来解决这些问题，采用来自沟通障碍、言语和运动科学的工具、方法和途径，发育神经科学、遗传学和干预研究。这四个相互关联的项目涉及以下目标。目标 1：识别深层口语背后的运动和神经机制语言障碍定义了自闭症儿童的最低限度语言能力。在同一组的两个项目中对于年幼的语言能力最低的儿童，我们计划使用状态来描述口腔和一般运动功能的特征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：进步我们对如何优化语言能力极差的幼儿的语言成果的理解自闭症谱系障碍。我们通过进行一项行为干预的随机对照试验来解决这个问题，该试验结合了社交沟通和口腔运动目标（项目 3），并跟踪目标 1 中研究的两个孩子多年来探索运动和神经功能的变化如何预测不同的语言途径（项目 1、2）。目标 3：调查与轻度言语自闭症谱系障碍相关的遗传风险因素，包括常见和罕见的变体（项目 4）。我们计划利用所有就读的孩子探索 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）。这些项目由行政核心统一并提供服务 (A) 以及将进行全面评估的临床和数据管理科学核心 (B) 使用现有的新颖措施来捕捉语言能力最低的儿童的异质表型患有自闭症谱系障碍。总之，我们中心进行的研究将显着增进我们对自闭症谱系这一被忽视的一端存在严重的沟通缺陷，发展出行为和预测语言不同发展途径的神经生物标志物，并可能突显潜力未来新型治疗干预的分子靶点。