Neural Markers of Language Development in Fragile X Syndrome and Autism Spectrum Disorder

脆性 X 综合征和自闭症谱系障碍语言发展的神经标志物

• 批准号: 9976735
• 负责人: Carol Lee Wilkinson
• 金额: $ 17.18万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9976735
• 关键词: 2 year old; 5 year old; Adult; Affect; Age; Animal Model; Area; Auditory; Auditory Evoked Potentials; Behavioral; Biological Markers; Boston; Brain; Child; Child Development; Clinical Trials; Cognitive; Cognitive deficits; Cohort Studies; Communities; Data; Detection; Development; Developmental Course; Diagnosis; Disease; Drug Targeting; Dyslexia; Electroencephalography; Electrophysiology (science); Enrollment; Environment; Epidemiology; Fragile X Syndrome; Frequencies; Funding; Future; Genes; Genetic Models; Goals; Impairment; Individual; Intellectual functioning disability; Intervention; K-Series Research Career Programs; Language; Language Delays; Language Development; Language Disorders; Lead; Learning; Measures; Mentors; Molecular; Monitor; National Institute on Deafness and Other Communication Disorders; Natural History; Neural Pathways; Neurobiology; Neurodevelopmental Disorder; Nursery Schools; Outcome; Participant; Pathway interactions; Pattern; Pediatric Hospitals; Phenotype; Physicians; Play; Population; Populations at Risk; Production; Research; Research Design; Research Personnel; Resources; Rest; Risk; Role; Scientist; Speech; Strategic Planning; Structure; Synaptic plasticity; Techniques; Training; Treatment Efficacy; Universities; Visit; Voice; aged; auditory processing; autism spectrum disorder; autistic children; base; boys; brain behavior; cognitive ability; cognitive neuroscience; cognitive skill; cognitive testing; cost; design; disability; endophenotype; experience; high risk; improved; language impairment; mouse model; neural network; neuroimaging; neuromechanism; outcome forecast; predictive marker; programs; relating to nervous system; response; social

PROJECT SUMMARY/ABSTRACT A child’s ability to communicate and learn through language plays a fundamental role in their cognitive, social, and functional development. Impairment in language development is shared across many neurodevelopmental disorders and can have a profound influence on a child’s future functional and developmental outcome. Unfortunately, our current understanding of the neurobiology underlying language deficits in neurodevelopmental disorders is limited, especially as it pertains to children with concurrent intellectual disability. In alignment with the strategic plan from NIDCD’s Voice, Speech, and Language program area, this project seeks to use EEG to identify neural markers (endophenotypes) associated with the progression and developmental course of speech and language impairments (Priority Area 2; Natural History and Epidemiology) in two understudied populations – children with Fragile X Syndrome (FXS) and minimally verbal children with autism spectrum disorder (ASD) (Priority Area 3; Understudied Populations). Neural markers identified through this study, could be used as biomarkers for prognosis, and treatment monitoring of language development for children with FXS and ASD, as well as inform new treatments (Priority Area 3: Detection, Diagnosis and Hypothesis-Driven Interventions). The proposed project has the following scientific goals: (1) Characterize electrophysiological similarities and differences across preschool-aged boys with FXS, ASD with language impairment, and typically developing boys; (2) Identify and characterize neural markers of concurrent language ability in FXS and ASD; and (3) Identify and characterize neural markers of future language acquisition in FXS and ASD. To do this, we will collect EEG in three groups of boys aged 2- to 5-years-old: 30 boys with FXS, 30 boys with idiopathic ASD with language impairment (n=30), and 30 typically developing boys. At the same visit and a second visit one year apart, participants will undergo language and cognitive assessments to determine their language development. The proposed project is supported by a world class team of mentors who are experts in developmental cognitive neuroscience, language development, and advanced EEG techniques. The research environment at Boston Children’s Hospital is exceptional and the surrounding intellectual resources at Harvard, Boston University, MGH, and MIT are unmatched. My training plan is specifically designed to provide advanced training in EEG analysis, auditory processing, and language assessments for minimally verbal children, that are crucial to investigating brain-behavior relationships in these heterogenous, understudied, at-risk populations. In addition, during my training I will gain practical experience in how to successfully manage longitudinal aspects of cohort study design. By the completion of the career development award, I will have successfully applied for R01-level funding and will be ready to transition to a fully independent physician-scientist.

项目摘要/摘要 孩子通过语言进行交流和学习的能力在认知，社会， 和功能发展。语言发展的障碍在许多神经发育中分享 疾病，可能会对孩子的未来功能和发展结果产生深远的影响。 不幸的是，我们目前对神经生物学潜在语言的理解定义了 神经发育障碍是有限的，尤其是与有智能的儿童有关 残疾。与NIDCD的声音，语音和语言程序领域的战略计划保持一致，这 项目旨在使用脑电图来识别与进展相关的神经标记（内型型） 言语和语言障碍的发展过程（优先区域2；自然历史和 流行病学）在两个知识的人群中 - 患有脆弱X综合征（FXS）的儿童和最小的言语 自闭症谱系障碍（ASD）的儿童（优先区域3；人口研究）。神经标记 通过这项研究确定，可以用作预后的生物标志物，语言的治疗监测 FX和ASD儿童的开发以及为新治疗提供信息（优先区域3：检测， 诊断和假设驱动的干预措施）。拟议的项目具有以下科学目标：（1） 表征有FXS的学龄前男孩的电生理相似性和差异，ASD 语言障碍，通常是发展男孩； （2）识别并表征并发的神经标记 FXS和ASD的语言能力； （3）识别和表征未来语言的神经标记 在FXS和ASD中获取。为此，我们将分别以2至5岁的男孩的三组收集脑电图：30 患有FXS的男孩，30个患有语言障碍的特发性ASD的男孩（n = 30），30个通常发育 男孩们。在同一访问和第二次访问中，参与者将接受语言和认知 评估以确定其语言发展。拟议的项目得到了世界一流的支持 导师团队是发展性认知神经科学，语言发展和 高级脑电图技术。波士顿儿童医院的研究环境非常出色， 在哈佛大学，波士顿大学，MGH和MIT周围的智力资源无与伦比。我的训练 计划专门设计用于提供脑电图分析，听觉处理和语言的高级培训 评估最小口头的儿童，这对于研究这些儿童至关重要 异源，理解，处于危险中。此外，在我的培训期间，我将获得实践经验 在如何成功管理队列研究设计的纵向方面。在职业生涯完成 开发奖，我将成功申请R01级资金，并准备过渡到 完全独立的身体科学家。