ConProject-002

ConProject-002

• 批准号: 10689733
• 负责人: CONNIE L. KASARI
• 金额: $ 32.05万
• 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/10689733
• 关键词: 3-Dimensional; Address; Age; Behavior; Behavior Therapy; Behavioral; Biological Markers; Boston; Brain; California; Child; Clinical; Clinical Management; Clinical Research; Collaborations; 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; 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; behavioral phenotyping; clinical practice; data management; endophenotype; evidence base; follow-up; genetic predictors; genetic risk factor; improved; innovation; joint attention; language impairment; language outcome; medical schools; minimally verbal; motor impairment; multidisciplinary; neglect; neural; neural correlate; neuromechanism; novel; novel therapeutic intervention; oral motor; predictive marker; rare variant; recruit; 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.

项目总结/摘要 许多患有ASD的儿童即使在接受高质量的干预措施后仍保持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，创新针对性 行为干预可以在一定程度上改善言语和社会沟通， 言语的孩子该中心位于波士顿大学和加州洛杉矶大学， 洛杉矶，是建立在我们早期的工作解决一个中心主题： ASD儿童在早期上学期间获得语言，我们如何才能 推动这种进步？我们从多学科的角度来处理这些问题， 从沟通障碍、言语和运动科学中提取的工具、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 以下目标。目的1：识别深层口语的运动和神经机制 语言障碍是自闭症儿童的最低语言障碍。在同一组的两个项目中 我们计划使用语言能力最低的儿童的语言能力状态来描述他们的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：推进 我们对如何优化语言能力最低的儿童的语言效果的理解， 自闭症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， 社会沟通和orphantic目标（项目3），并通过跟踪目标1中研究的儿童两个 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）。目的3：研究与最小语言ASD相关的遗传风险因素， 包括常见和罕见的变体（项目4）。我们计划利用参加所有 项目探索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，并由一个行政核心服务 (A)以及临床和数据管理科学核心（B），将进行全面评估 使用现有的和新的措施，以捕捉异质性表型的最低语言儿童 关于ASD总之，在我们中心进行的研究将大大促进我们对 在自闭症谱系中被忽视的一端，严重的沟通缺陷， 神经生物标志物预测语言的不同发育途径，并可能突出潜在的 未来新型治疗干预的分子靶点。