ConProject-001

基本信息

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
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/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

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.

项目摘要/摘要即使接受质量干预措施后，许多ASD的儿童即使是口头上的最低言语。最近的研究强调了这一组的异质性，证实没有任何机制可以解释其严重沟通不足的根本原因。同时，创新的目标行为干预措施可以最少导致语音和社交交流的改善口头孩子。该中心的目标位于波士顿大学和加利福尼亚大学洛杉矶分校安吉利斯（Angeles）是基于我们较早的作品解决中心主题的基础：哪个年轻的口头 ASD的孩子在早期学年就获得收购语言，我们如何才能促进这样的进步？我们从多学科的角度解决这些问题，采用沟通障碍，言语和运动科学汲取的工具，方法和方法，发育神经科学，遗传学和干预研究。四个互连项目地址以下目标。目的1：确定口语深刻的运动和神经机制语言障碍定义了自闭症的最低言语儿童。在同一小组的两个项目中我们计划使用最低的口头和一般运动功能来表征年轻的言语儿童 ART技术和电生理学探测神经功能（项目1，2）。目标2：前进我们对如何优化年轻言语儿童的语言结果的理解 ASD。我们通过对联合行为干预的随机对照试验来解决这一问题社会交流和眼动目标（项目3），并跟随在AIM 1中学习的孩子，供两个探索运动和神经功能的变化如何预测多种语言途径（项目1，2）。目标3：研究与最小言语ASD相关的遗传危险因素，包括常见和稀有变体（项目4）。我们计划利用所有参加的孩子探索ASD常见多基因风险的定量负载之间的关系的项目语言，运动和神经表型以及对治疗反应的遗传预测指标以及更多最佳发展成果（所有项目）。这些项目是团结的，由行政核心服务（a）以及将进行全面评估的临床和数据管理科学核心（b）使用可用的和新颖的措施来捕获最低言语儿童的异质表型与ASD。一起，我们中心进行的研究将大大提高我们对在自闭症谱系中被忽视的末端的深刻沟通缺陷，发展行为和神经生物标志物预测语言的不同发育途径，并可能突出潜力未来新型治疗干预措施的分子靶标。