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

项目概要/摘要 儿童通过语言进行交流和学习的能力在他们的认知、社交、 功能发展。语言发育障碍在许多神经发育障碍中是共同的。 这些疾病可能对儿童未来的功能和发育结果产生深远的影响。 不幸的是，我们目前对语言缺陷背后的神经生物学的理解， 神经发育障碍是有限的，特别是因为它涉及到并发智力障碍的儿童， 残疾。根据NIDCD的语音，语音和语言计划领域的战略计划， 该项目旨在使用EEG来识别与进展相关的神经标记物（内表型）， 言语和语言障碍的发展过程（优先领域2;自然历史和 流行病学）在两个未充分研究的人群-脆性X综合征（FXS）和最低限度语言的儿童 自闭症谱系障碍（ASD）儿童（优先领域3;未充分研究人群）。神经标志物 通过这项研究确定，可以作为预后的生物标志物， FXS和ASD儿童的发展，以及告知新的治疗方法（优先领域3：检测， 诊断和假设驱动的干预）。本项目的科学目标如下：（1） 描述患有FXS、ASD和FXS的学龄前男孩之间的电生理相似性和差异， 语言障碍，通常是发育中的男孩;（2）识别和表征并发性语言障碍的神经标志物， FXS和ASD语言能力;（3）识别和表征未来语言的神经标记 收购FXS和ASD。为此，我们将收集三组2至5岁男孩的EEG：30 FXS男孩，30名患有语言障碍的特发性ASD男孩（n=30），30名典型的发展中国家儿童（n=30）， 小伙子们在同一次访视和间隔一年的第二次访视中，参与者将接受语言和认知测试。 评估以确定他们的语言发展。该项目得到了世界级 由发展认知神经科学、语言发展和 先进的脑电图技术波士顿儿童医院的研究环境是特殊的， 哈佛、波士顿大学、麻省理工学院和麻省理工学院的周边智力资源是无与伦比的。我的训练 该计划是专门为提供脑电图分析、听觉处理和语言方面的高级培训而设计的 评估最低限度的语言儿童，这是至关重要的调查大脑行为的关系，在这些 异质的、未被充分研究的、处于危险中的人群。此外，在培训期间，我将获得实践经验 如何成功管理队列研究设计的纵向方面。在职业生涯结束时， 发展奖，我将成功申请R 01级资金，并将准备过渡到一个 完全独立的科学家。

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.