Neuroanatomical endophenotypes in Persistent Developmental Stuttering

持续性发育性口吃的神经解剖学内表型

• 批准号: 7425894
• 负责人: MATTHEW DANIEL CYKOWSKI
• 金额: $ 5.48万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7425894
• 关键词: Adult; Adult Stuttering; Affect; Age; Age-Years; Agreement; Anatomy; Anisotropy; Anterior; Architecture; Area; Behavioral; Brain; Child; Childhood; Complement; Complex; Control Groups; Corpus Callosum; Data; Development; Developmental Stuttering; Diagnostic; Diffusion Magnetic Resonance Imaging; Diffusion weighted imaging; Disease; Family member; Female; Foundations; Future; Gender; Genes; Genetic; Goals; Hereditary Disease; Image; Image Analysis; Incidence; Individual; Invasive; Knowledge; Language Disorders; Lead; Left; Location; Magnetic Resonance Imaging; Maps; Measures; Methods; Mission; Motor; Nature; Pattern; Phenotype; Population; Predisposition; Programming Languages; Reporting; Research; Resolution; Solid; Speech; Speech Disorders; Structure; Stuttering; Surface; Susceptibility Gene; Symptoms; System; Techniques; Testing; Therapeutic; Thick; Variant; Voice; Work; base; brain morphology; cost; developmental disease; endophenotype; falls; genetic linkage analysis; improved; interest; interhemispheric transfer; male; neuroimaging; novel; novel diagnostics; relating to nervous system; sound; statistics; tool; trait; transmission process; white matter

DESCRIPTION (provided by applicant): Persistent developmental stuttering (PDS) affects 1% of the adult population with a lifetime incidence of approximately 4%. The major aim of this application is to identify quantitative neuroanatomical endophenotypes associated with PDS. Endophenotypes are susceptibility-related phenotypes, even in individuals who do not overtly display symptoms of a disorder. Linkage analysis of stuttering can use endophenotypes to understand the genes implicated, an approach now taken in many complex genetic disorders. Knowing the genes predisposing susceptibility to PDS will aid in the understanding and treatment of the disorder. Understanding the nature and cause of PDS is one of the missions of the NIDCD, Voice, Speech, and Language Program. The proposed work also falls in line with other stated goals of the NIDCD, such as understanding the genetic bases of language disorders in childhood, a natural future extension of this work. There are two specific aims in the application which will complement the solid foundation of behavioral and neurophysiologic traits of adults who stutter (AWS) with quantitative neuroanatomical traits. This is based on the reasoning that: PDS is a complex genetic disorder, endophenotypes are now routinely used to study such disorders, brain morphology has several highly heritable features, and preliminary studies suggest PDS is associated with subtle cortical folding abnormalities. Specific Aim 1 of this project will characterize the cortical thickness (Aim 1A) and regional gyrification profiles (Aim 1B) of AWS. This will be done by rater-indendent means using automated image analysis tools. Additionally, diffusion-weighted imaging will be employed in Specific Aim 2 to assess the connectional architecture of the brain, through tract-based comparisons (Aim 2A) and a tract-tracing approach to the corpus callosum (Aim 2B). The studies of Aim 2A are appropriate because studies of AWS have described focused abnormalities in the left hemisphere speech system with diffusion tensor imaging. The proposed work will attempt to first replicate, and then extend, this potential endophenotype. Additionally, tractography methods will be used to evaluate hypothesized aberrant connections within the corpus callosum, a highly heritable structure. These studies will provide a rater-independent, cost-effective, minimally-invasive tool for dissecting the genes involved in susceptibility to the disorder. RELEVANCE: Developmental stuttering is a speech disorder affecting both children and adults. It is known to have a genetic basis, but the genes involved are still largely unknown. Understanding the genetic basis of the disorder will help improve diagnostic approaches and treatment strategies.

描述（由申请人提供）：持续性发育性口吃（PDS）影响1%的成年人群，终生发病率约为4%。本申请的主要目的是确定与PDS相关的定量神经解剖学内表型。内表型是易感性相关的表型，即使在没有明显表现出病症症状的个体中也是如此。口吃的连锁分析可以使用内在表型来了解相关的基因，这是目前许多复杂遗传疾病所采用的方法。了解导致PDS易感性的基因将有助于理解和治疗这种疾病。了解PDS的性质和原因是NIDCD，语音，言语和语言计划的使命之一。拟议的工作也福尔斯符合NIDCD的其他既定目标，如了解儿童语言障碍的遗传基础，这是这项工作的自然未来延伸。有两个具体的目标，在应用程序中，这将补充坚实的基础上的行为和神经生理特征的成年人口吃（AWS）与定量神经解剖特征。这是基于以下推理：PDS是一种复杂的遗传疾病，内表型现在通常用于研究此类疾病，脑形态具有几个高度遗传的特征，初步研究表明PDS与细微的皮质折叠异常有关。本项目的具体目标1将描述AWS的皮质厚度（目标1A）和区域旋转轮廓（目标1B）。这将使用自动图像分析工具通过独立于评级者的方法完成。此外，将在特定目标2中采用弥散加权成像，通过基于神经束的比较（目标2A）和胼胝体神经束追踪方法（目标2B）评估大脑的连接结构。Aim 2A的研究是适当的，因为AWS的研究描述了扩散张量成像左半球语音系统的聚焦异常。拟议的工作将试图首先复制，然后扩展这种潜在的内在表型。此外，纤维束成像方法将用于评估胼胝体（一种高度遗传的结构）内的假设异常连接。这些研究将提供一种独立于评估者的、具有成本效益的、微创的工具，用于解剖与疾病易感性相关的基因。相关性：发育性口吃是一种影响儿童和成人的言语障碍。已知它有遗传基础，但所涉及的基因在很大程度上仍然未知。了解这种疾病的遗传基础将有助于改善诊断方法和治疗策略。

项目成果

A study of the reproducibility and etiology of diffusion anisotropy differences in developmental stuttering: a potential role for impaired myelination.

• DOI: 10.1016/j.neuroimage.2010.05.011
• 发表时间: 2010-10-01
• 期刊: NEUROIMAGE
• 影响因子: 5.7
• 作者: Cykowski, M. D.;Fox, P. T.;Ingham, R. J.;Ingham, J. C.;Robin, D. A.
• 通讯作者: Robin, D. A.