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

摘要 唐氏综合症(DS)是导致智力残疾的主要已知原因，也是一种高度公认的基因 一种涉及多种医学并存的综合征。据估计，DS患者听力障碍的发生率高达 80%-90%的人被认为是由脑部结构和功能异常共同引起的 外耳、中耳和/或内耳。本项目旨在解决有关角色的一个及时而重要的问题 DS患者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听力障碍的普遍性质，但到目前为止，研究还没有 确定与21三体相关的听力障碍的具体后果。目标1将评估听力状况， 用皮层下听觉加工的客观测量方法评价听觉完整性和成熟度 脑干反应和皮层听觉诱发电位及其功能加工 语音识别和声音定位的行为测量。我们的目标是了解听力损失是如何 DS患者的听觉加工和听觉成熟是在听力损失补偿后发生的。目标2将 调查听力/听力障碍与整体智力功能之间的关系 记忆、注意力和执行功能，因为这些认知域已经被证明在 非DS人群中听力状况和听力障碍的关键途径。Aim 2还将研究 听力和听觉功能与接受性和表现性词汇之间的联系，通过 标准化的衡量标准和语言样本。目标3将调查听力和听觉之间的联系 涉及听觉过程的大脑区域的结构和微结构的缺陷和成像测量， 侧重于区域形态测量、驰豫测量和微观结构扩散测量。我们的目标是了解 异常是听觉过程中特定的区域，是所有听觉脑区的全局异常，还是 一般/全局到DS大脑，但不是听觉特定的，即与 DS.这项工作符合在整个生命周期内研究共生疾病的规划目标 了解唐氏综合症(包括)并将促进对听力损失后果的理解 在DS的功能听觉、认知和语言结果以及大脑完整性方面。一个直接的好处是 结果将为针对病理生理学的听力损失的临床评估和干预提供依据。 在DS中。较长期的影响是确定评估未来干预措施有效性的措施 DS中的听力损失。

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.