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

项目摘要/摘要 儿童通过语言进行交流和学习的能力在他们的认知、社交和学习能力中起着至关重要的作用， 和功能开发。语言发育障碍在许多神经发育中都存在 这可能会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，尤其是与智力同时存在的儿童有关。 残疾。与NIDCD的语音、演讲和语言项目领域的战略计划保持一致，这 该项目寻求使用EEG来识别与疾病进展相关的神经标记(内表型)和 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)在两个未被研究的人群--脆性X综合征(FXS)儿童和最少言语的儿童中 患有自闭症谱系障碍(ASD)的儿童(优先领域3；未充分研究的人群)。神经标志物 经本研究鉴定，可作为语言预后和治疗监测的生物标志物 FXS和ASD儿童的发展，以及通知新的治疗方法(优先领域3：检测， 诊断和假设驱动的干预)。拟议的项目有以下科学目标：(1) FXS、ASD、FXS和ASD学龄前男童的电生理学异同 语言障碍，通常是发育中的男孩；(2)识别和表征并发的神经标记物 FXS和ASD的语言能力；(3)识别和表征未来语言的神经标记物 收购FXS和ASD。为了做到这一点，我们将收集三组2至5岁男孩的脑电：30 患有FXS的男孩，30名患有特发性ASD并语言障碍的男孩(n=30)，以及30名典型的发展中的男孩 孩子们。在同一次访问和相隔一年的第二次访问中，参与者将接受语言和认知 评估以确定他们的语言发展。拟议的项目得到了世界级的支持 导师团队是发展认知神经科学、语言发展和 先进的脑电技术。波士顿儿童医院的研究环境非常特殊， 哈佛大学、波士顿大学、麻省理工学院和麻省理工学院的智力资源无与伦比。我的训练 该计划专门为提供脑电分析、听觉处理和语言方面的高级培训而设计 对言语最少的儿童的评估，这对研究这些儿童的大脑-行为关系至关重要 异质、未被充分研究、处于危险中的人群。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。通过职业生涯的完成 获得发展奖后，我将成功申请R01级资金，并将准备过渡到 完全独立的内科医生兼科学家。

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.