Auditory function, cognition, language and brain structure in Down Syndrome

唐氏综合症的听觉功能、认知、语言和大脑结构

• 批准号: 10391010
• 负责人: ANDREW L ALEXANDER
• 金额: $ 228.18万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-01-15 至 2026-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10391010
• 关键词: 16 year old; Address; Adult; Age; Atrophic; Attention; Auditory; Auditory Brainstem Responses; Auditory Evoked Potentials; Auditory Perception; Brain; Brain Stem; Brain region; Child; Clinical assessments; Cognition; Cognitive; Data; Diffusion; Down Syndrome; External Ear; Functional disorder; Future; Genetic; Goals; Guidelines; Head; Hearing; Hearing problem; High Prevalence; Image; Impaired cognition; Impairment; Individual; Intellectual functioning disability; Intelligence; Intervention; Investigation; Labyrinth; Language; Longevity; Measures; Medical; Memory; Motion; Nature; Parietal Lobe; Pathway interactions; Perception; Performance; Pharmacologic Substance; Population; Process; Research; Role; Sampling; Sound Localization; Speech; Statistical Models; Structure; Syndrome; Techniques; Temporal Lobe; Thalamic structure; Therapeutic Trials; Time; Vocabulary; Work; aged; auditory processing; behavior measurement; brain abnormalities; clinical diagnosis; clinical practice; cognitive performance; cohort; comorbidity; dementia risk; design; effectiveness evaluation; executive function; frontal lobe; functional outcomes; hearing impairment; language outcome; meetings; middle ear; morphometry; novel; parallel processing; standardize measure; white matter; young adult

ABSTRACT Down syndrome (DS) is a leading known cause of intellectual disability and a highly recognized genetic syndrome that involves multiple medical co-morbidities. Hearing deficits in DS are estimated to occur up to rates of 80-90% and are thought to be caused by a combination of structural and functional abnormalities in the external, middle and/or inner ear. This project aims to tackle a timely and significant question regarding the role of hearing loss in DS on auditory function, cognition, language, and structural integrity of brain regions that are important for hearing. Despite the known pervasive nature of hearing deficits in DS, to date, research has yet to identify specific consequences of hearing deficits associated with trisomy 21. Aim 1 will assess hearing status, auditory integrity and maturation using objective measures of auditory processing in subcortical auditory brainstem responses (ABR) and cortical auditory evoked potentials (CAEPs), and functional processing behavioral measures of speech identification and sound localization. The goal is to understand how hearing loss impacts auditory processing and auditory maturation in DS is after compensating for hearing loss. Aim 2 will investigate the associations between hearing/auditory deficits and overall intellectual functioning as well as memory, attention, and executive function, as these cognitive domains have been shown to be influenced in critical ways by hearing status and auditory impairments in non-DS populations. Aim 2 will also examine the associations between hearing and auditory function and receptive and expressive vocabulary, obtained via standardized measures and language samples. Aim 3 will investigate the associations between hearing/auditory deficits and imaging measures of structure and microstructure in brain regions involved in auditory processes, focusing on regional morphometry, relaxometry, and microstructural diffusion measures. We aim to understand whether abnormalities are domain specific within auditory processes, global to all auditory brain regions, or generalized/global to DS brains but not auditory-specific, i.e., related to issues from generic pathophysiology in DS. This work meets the programmatic objectives of INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndrome (INCLUDE) and will advance understanding of the consequences of hearing loss in DS for functional auditory, cognitive and language outcomes and brain integrity. One immediate benefit is that results will inform clinical assessment and intervention of hearing loss catered specifically to the pathophysiology in DS. Longer-term impact is the identification of measures to evaluate effectiveness of future intervention of hearing loss in DS.

摘要 唐氏综合征（DS）是智力残疾的主要已知原因，也是一种高度公认的遗传病。 涉及多种医学共病的综合征。据估计，DS的听力障碍发生率高达 80-90%，被认为是由结构和功能异常的组合引起的。 外耳、中耳和/或内耳。该项目旨在解决一个及时和重要的问题， DS中听力损失对听觉功能，认知，语言和大脑区域结构完整性的影响， 对听力很重要。尽管已知DS中听力缺陷的普遍性，但迄今为止，研究尚未 确定与21三体相关的听力缺陷的具体后果。目标1将评估听力状态， 在皮层下听觉系统中使用听觉处理的客观测量的听觉完整性和成熟度 脑干反应（ABR）和皮层听觉诱发电位（CAEP），以及功能处理 语音识别和声音定位的行为测量。目标是了解听力损失是如何 影响DS的听觉加工和听觉成熟是在补偿听力损失之后。目标2将 研究听力/听觉缺陷与整体智力功能之间的关系， 记忆力、注意力和执行功能，因为这些认知领域已被证明会受到 非DS人群的听力状况和听觉障碍的关键方式。目标2还将审查 听力和听觉功能与接受性和表达性词汇之间的联系，通过 标准化措施和语言样本。目标3将研究听力/听觉 听觉过程相关脑区的结构和微结构的缺陷和成像测量， 侧重于区域形态测量、弛豫测量和微观结构扩散测量。我们的目标是了解 异常是否是听觉过程中的特定领域，是否是所有听觉脑区的全局性异常，或 广义/全局到DS脑，但不是神经系统特异性的，即，有关的问题，从一般病理生理学， DS.这项工作符合调查整个生命周期中同时发生的情况的计划目标 了解唐氏综合征（包括），并将促进对听力损失后果的理解 在DS中用于功能性听觉、认知和语言结果以及大脑完整性。一个直接的好处是， 结果将为专门针对病理生理学的听力损失的临床评估和干预提供信息。 在DS。长期影响是确定措施，以评估未来干预措施的有效性， 听力损失在DS