Neurobiological Markers of Rhythm: Risk and Resilience for Language Acquisition

节奏的神经生物学标记：语言习得的风险和弹性

基本信息

批准号：
10377901
负责人：
Reyna Leigh Gordon
金额：
$ 60.64万
依托单位：
VANDERBILT UNIVERSITY MEDICAL CENTER
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：
2019-02-01 至 2024-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10377901
关键词：
Academy Affect Alpha Rhythm Area Attention Automobile Driving Behavioral Biological Biology Brain Child Clinical Data Cognition Communication Communication impairment Complex DNA Data Data Set Development Disease Dyslexia Expectancy Foundations Future Genes Genetic Genetic Markers Genetic Models Genetic Predisposition to Disease Genomic approach Genomics Heritability Human Impairment Internet Intervention Investigation Joints Knowledge Language Language Development Language Development Disorders Language Disorders Life Link Mendelian randomization Meta-Analysis Methodological Studies Methods Modeling Music National Institute on Deafness and Other Communication Disorders Neurobiology Patient Self-Report Pattern Perception Periodicity Phenotype Process Quality of life Quantitative Genetics Reporting Research Risk Risk Factors Role Sample Size Sampling Schools Series Social outcome Speech Stimulus Structure Stuttering Task Performances Testing Time Trees Vocabulary Work base behavioral plasticity brain pathway clinically significant comorbidity directed attention experimental study genetic architecture genetic predictors genome analysis genome wide association study improved innovation insight interdisciplinary approach laboratory experiment language impairment novel personalized medicine predictive modeling public health relevance relating to nervous system repository resilience response skills social sound specific biomarkers specific language impairment success syntax theories tool trait

项目摘要

PROJECT SUMMARY. Specific Language impairment (SLI) is a common, life-long communication disorder characterized by difficulties acquiring grammar and vocabulary that affect children's quality of life, success in school, and livelihood. There is an urgent need to increase identification and treatment of children with SLI. Although SLI is known to be heritable, the underlying neurobiology of the disorder is not yet clear. Recent work by the PI has shown robust associations between rhythm and grammar traits in children, pointing to rhythm resilience as a variable involved in spoken grammar skills. Emerging evidence in the field points to co-morbid rhythm deficits and grammatical deficits in SLI, pointing to weaknesses in rhythm sensitivity as an SLI risk factor. Furthermore, rhythm and grammatical traits are both heritable, and both involve dynamically orienting attention to hierarchical structure over time, but no prior study has directly compared the genetic basis of rhythm and grammar. Here we take an understudied but promising approach to investigating potentially shared genetic architecture to rhythm deficits and SLI. Since sound patterns (across species) used to communicate are organized rhythmically, it is highly likely that present-day speech and language capacities are built on pre- existing genetic architecture for communication, which may include the rhythmic aspect of communication. Children with SLI may thus have heritable rhythm deficits that impair their ability (via common neurobiology) to process the structure of language during grammatical acquisition. The present proposal integrates new methods of genome analysis with rhythm cognition experiments aimed at understanding the mechanisms underlying the potential contribution of rhythm deficits to SLI. Aim 1 harnesses large-sample bio-repositories and extant data with Genome-Wide Association Studies (GWAS) methodology to characterize the genetic architecture of developmental language disorder. This approach allows us to construct the largest sample sizes yet for developing a genetic prediction model for SLI and to investigate the clinical significance of genes involved in SLI. Aim 2 utilizes a GWAS approach in a novel dataset to provide important new knowledge on the genetic basis of rhythm. Armed with novel knowledge about the neurobiological markers of SLI and rhythm deficits, we will then investigate a potential influence of rhythm on grammar-related traits (Aim 3a) and grammar states (Aim 3b), using an innovative selection of genomic analyses and a series of targeted laboratory experiments in children with SLI. By testing this framework of rhythm risk and resilience, these studies lay essential groundwork for multiple future avenues of improving identification and treatment of children with SLI. This project directly responds to NIDCD's call to identify genetic factors and co-occurring conditions that contribute to language impairment and to develop biomarkers of SLI. Moreover, new knowledge of the genetic basis of rhythm may also have relevance for other communication disorders that have co-morbid rhythm deficits (e.g., stuttering, dyslexia).

项目摘要。特定语言障碍 (SLI) 是一种常见的、终生的沟通障碍其特点是难以获取语法和词汇，影响儿童的生活质量、成功学校、生活。迫切需要加强对 SLI 儿童的识别和治疗。尽管已知 SLI 具有遗传性，但该疾病的神经生物学基础尚不清楚。最近的工作 PI 的研究表明，儿童的节奏和语法特征之间存在密切的关联，指出节奏弹性作为口语语法技能的一个变量。该领域的新证据表明存在共病 SLI 中的节律缺陷和语法缺陷，表明节律敏感性薄弱是 SLI 的风险因素。此外，节奏和语法特征都是可遗传的，并且都涉及动态定向随着时间的推移，人们关注等级结构，但之前没有研究直接比较过节奏和语法。在这里，我们采用一种尚未充分研究但有希望的方法来调查潜在的共享节律缺陷和 SLI 的遗传结构。由于声音模式（跨物种）用于交流是有节奏地组织起来的，现在的言语和语言能力很可能是建立在前人的基础上的。现有的沟通遗传结构，其中可能包括沟通的节奏方面。因此，患有 SLI 的儿童可能患有遗传性节律缺陷，从而损害了他们的能力（通过常见的神经生物学）在语法习得过程中处理语言结构。目前的提案整合了新的通过节律认知实验进行基因组分析的方法旨在了解其机制节律缺陷对 SLI 的潜在影响。目标 1 利用大样本生物样本库和现有数据与全基因组关联研究（GWAS）方法来表征遗传发展性语言障碍的体系结构。这种方法使我们能够构建最大的样本开发 SLI 的遗传预测模型并研究基因的临床意义涉及SLI。目标 2 在新颖的数据集中利用 GWAS 方法来提供有关以下方面的重要新知识：节律的遗传基础。掌握有关 SLI 和节律的神经生物学标记的新知识缺陷，然后我们将研究节奏对语法相关特征的潜在影响（目标 3a）和语法状态（目标 3b），使用基因组分析的创新选择和一系列有针对性的 SLI 儿童的实验室实验。通过测试这个节奏风险和弹性框架，这些研究为未来改善识别和治疗的多种途径奠定了重要基础患有 SLI 的儿童。该项目直接响应 NIDCD 识别遗传因素和共存疾病的号召导致语言障碍和形成 SLI 生物标志物的条件。而且，新知识节律遗传基础的研究也可能与其他共病的沟通障碍有关节律缺陷（例如口吃、阅读障碍）。