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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：
10559638
负责人：
Reyna Leigh Gordon
金额：
$ 61.4万
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 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10559638
关键词：
Academy Acquired Language Disorders Affect Area Attention Automobile Driving Behavioral Biological Biology Brain Child Clinical Data Cognition Communication Communication impairment Complex DNA Data Data Set Development Disease Dyslexia Education 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 Link Mendelian randomization 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 biobank 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 neural novel personalized medicine predictive modeling public health relevance 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。特殊语言障碍是一种常见的、终身的交流障碍其特点是难以获得影响儿童生活质量的语法和词汇，学校，生活。迫切需要增加对SLI儿童的识别和治疗。虽然SLI是已知的遗传性，但这种疾病的潜在神经生物学尚不清楚。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着强有力的联系，弹性作为一个变量参与口语语法技能。新的证据表明 SLI的节奏缺陷和语法缺陷，指出节奏敏感性的弱点是SLI的风险因子此外，节奏和语法特征都是可遗传的，都涉及动态定向随着时间的推移，人们注意到了等级结构，但没有先前的研究直接比较了节奏和语法。在这里，我们采取了一种研究不足但有前途的方法来调查潜在的共享遗传结构对节律缺陷和SLI的影响。由于声音模式（跨物种）用于交流是有节奏地组织起来的，很可能现在的言语和语言能力是建立在前现有的遗传结构的沟通，其中可能包括节奏方面的沟通。因此，SLI儿童可能具有遗传性节律缺陷，这损害了他们（通过常见的神经生物学）在语法习得过程中处理语言结构。本提案纳入了新的基因组分析方法与节奏认知实验旨在了解机制潜在的节律缺陷对SLI的贡献。Aim 1利用大样本生物储存库和现存的数据与全基因组关联研究（GWAS）方法来表征遗传发育性语言障碍的结构。这种方法使我们能够构建最大的样本为建立SLI的遗传预测模型和研究基因的临床意义，参与SLI。目标2在一个新的数据集中利用GWAS方法，提供关于节奏的遗传基础掌握了SLI和节律的神经生物学标志物的新知识缺陷，然后我们将研究节奏对语法相关性状的潜在影响（目标3a），语法状态（目标3b），使用创新的基因组分析选择和一系列有针对性的 SLI儿童的实验室实验。通过测试这种节奏风险和弹性的框架，这些研究为今后改善艾滋病毒/艾滋病的识别和治疗的多种途径奠定了重要基础。 SLI患儿该项目直接响应NIDCD的号召，以确定遗传因素和共同发生的有助于语言障碍的条件，并开发SLI的生物标志物。此外，新知识节奏的遗传基础也可能与其他交流障碍有关，节律缺陷（例如，口吃、诵读困难）。

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Using neuroimaging genomics to investigate the evolution of human brain structure.

DOI：
10.1073/pnas.2200638119
发表时间：
2022-10-04
期刊：
Proceedings of the National Academy of Sciences of the United States of America
影响因子：
11.1
作者：
通讯作者：

Using a polygenic score in a family design to understand genetic influences on musicality.

DOI：
10.1038/s41598-022-18703-w
发表时间：
2022-08-29
期刊：
SCIENTIFIC REPORTS
影响因子：
4.6
作者：
Wesseldijk, Laura W.;Abdellaoui, Abdel;Gordon, Reyna L.;Ullen, Fredrik;Mosing, Miriam A.
通讯作者：
Mosing, Miriam A.

Does rhythmic priming improve grammatical processing in Hungarian-speaking children with and without developmental language disorder?