The effects of aging and hearing loss on human auditory cortex

描述(由申请人提供)： 人类听觉皮质(HAC)是一个复杂的区域，包含多个功能专门化的听觉皮质区域(ACF)。阐明ACFS的组织计划和功能特性对于理解声音知觉的皮质机制是必要的。我们提出了四个实验来阐明人类ACF的结构和功能组织，并表征其因衰老和感音神经性耳聋(SNHL)而引起的解剖和功能特性的变化。研究对象分为三组：(1)听力正常的青年受试者；(2)听力正常的老年受试者；(3)双侧感音神经性耳聋(SNHL)的老年受试者。每个受试组将参加四个实验。在之前的授予期间，我们分析了HAC的组织结构，以揭示人类ACFS的组织计划。HAC的组织结构与其他灵长类物种相似：它由12个ACF组成，其中3个核心ACF以立体结构组织，周围有7条带和2个Parabelt ACF。在实验中1，我们将使用最先进的MRI扫描仪复制和扩展这些发现。我们将从年轻受试者那里获得数据，并评估与年龄和SNHL相关的ACF立位组织、强度函数、频率调谐带宽、空间调谐和注意调制的变化。语言处理受到年龄的影响，特别是与SNHL相关的情况下。我们先前发现，外侧带ACF专门用于处理语音，而内侧带ACF专门用于处理复杂的非语音刺激。在实验中2，我们将映射由口语音节和各种控制刺激产生的激活，以阐明侧向ACF中的言语加工专门化。我们还将测量由于衰老和SNHL而导致的语音刺激激活模式的变化。我们实验室以前的研究和试点数据证明了HAC解剖学中与年龄相关的变化，并表明它们与听觉感知能力相关。我们开发了许多创新技术来定量分析大脑皮层的解剖结构。在实验中3，我们将使用这些技术通过测量皮质厚度和组织特性来表征与年龄和SNHL相关的HAC变化，这些特性反映了树突密度、皮质周围纤维组织和髓鞘形成。为了评估这些变化的行为相关性，我们开发了新的噪音和听觉短期言语记忆中的语音理解测试，发现这些能力会随着年龄的增长而受损，特别是在SNHL患者中。在实验中我们将使用这些测试和其他测试来量化三个受试组的听觉感知能力。结果将与实验中看到的功能激活模式相关联。1和2，并在实验中测量了HAc的解剖结构。3.意义。与年龄相关的言语理解障碍是患有和不患有听力损失的老年退伍军人最常见的抱怨之一。这项研究计划将阐明年龄和SNHL相关言语知觉损害的解剖学和功能基础。此外，它还将提供必要的规范性数据，以澄清HAC的基本解剖和功能组织。这些结果将提高HAC神经成像研究的精确度，HAC与包括耳鸣、中风、痴呆症、自闭症、精神分裂症和创伤性脑损伤(TBI)在内的各种听力、神经和精神疾病有关。 公共卫生相关性： 项目简介这项为期4年的研究计划的目标是使用结构和功能磁共振来阐明年轻退伍军人、听力正常的老年退伍军人和听力受损的老年退伍军人的听觉皮质的组织计划。我们将阐明听觉皮质如何处理简单和复杂的声音，特别是语音。随着退伍军人年龄的增长，言语理解困难对他们的影响越来越大。用相互竞争的信息进行的语音理解测试显示，90%的60-69岁退伍军人存在异常。我们创新的神经成像和行为测试方法将阐明听觉皮质的异常，这些异常是患有和不伴有听力损失的老年受试者语音处理受损的基础。此外，它们还将允许对其他常见疾病(如脑外伤、精神分裂症、耳鸣和痴呆症)中听觉皮质的异常进行更精细的研究，在这些疾病中，听觉皮质起着核心作用。

DESCRIPTION (provided by applicant): Human auditory cortex (HAC) is a complex area that contains multiple, functionally specialized auditory cortical fields (ACFs). Elucidating the organizational plan and functional properties of ACFs is necessary for understanding the cortical mechanisms of sound perception. We propose four experiments to elucidate the structural and functional organization of human ACFs and characterize changes in their anatomy and functional properties caused by aging and sensorineural hearing loss (SNHL). Three groups of subjects will be studied: (1) Young subjects with normal hearing; (2) Older subjects with normal hearing; and (3) Older subjects with mild to moderate bilateral sensorineural hearing loss (SNHL). Each subject group will participate in four experiments. During the previous granting period, we analyzed the tonotopic organization of HAC to reveal the organizational plan of human ACFs. HAC has an organization similar to that of other primate species: it contains 12 ACFs with three tonotopically organized core ACFs, surrounded by seven belt and two parabelt ACFs. In Exp. 1, we will replicate and extend these findings using a state-of-the-art MRI scanner. We will data from young subjects and evaluate age- and SNHL- related changes in ACF tonotopic organization, intensity functions, frequency-tuning bandwidths, spatial tuning, and attentional modulation. Speech processing is compromised by aging, particularly in association with SNHL. We previously found that lateral belt ACFs were specialized for processing speech sounds while medial belt ACFs were specialized for processing complex non-speech stimuli. In Exp. 2, we will map activations produced by spoken syllables and various control stimuli to elucidate speech-processing specialization in lateral ACFs. We will also measure changes in activation patterns to speech stimuli due to aging and SNHL. Previous studies and pilot data from our lab demonstrate age-related changes in HAC anatomy and shown that they correlate with auditory perceptual abilities. We have developed a number of innovative techniques to quantitatively analyze the anatomical structure of the cortex. In Exp. 3, we will use these techniques to characterize age- and SNHL-related alterations in HAC by measuring cortical thickness and tissue properties that reflect dendritic density, pericortical fiber organization and myelination. To evaluate the behavioral relevance of these changes we have developed new tests of speech comprehension in noise and auditory short- term verbal memory and found that these abilities are compromised by aging, particularly in patients with SNHL. In Exp. 4, we will use these and other tests to quantify auditory perceptual abilities in the three subject groups. The results will be correlated with the pattern of functional activations seen in Exps. 1 and 2 and with HAC anatomical structure measured in Exp. 3. Significance. Age-related impairments in speech comprehension are among the most common complaints of older veterans with and without hearing loss. This research program will elucidate the anatomical and functional basis of age- and SNHL-related impairments in speech perception. In addition, it will provide essential normative data that will clarify the basic anatomical and functional organization of HAC. The results will improve the precision of neuroimaging studies of HAC that has been implicated in a variety of audiological, neurological and psychiatric disorders including tinnitus, stroke, dementia, autism, schizophrenia, and traumatic brain injury (TBI). PUBLIC HEALTH RELEVANCE: Project Narrative The goal of this 4-yr research program is to use structural and functional MRI to clarify the organizational plan of auditory cortex in young Veterans, older Veterans with normal hearing, and older Veterans with hearing loss. We will clarify how auditory cortex processes both simple and complex sounds, particularly speech. Difficulties in speech comprehension affect Veterans increasingly as they age. Tests of speech comprehension with competing messages show abnormalities in 90% of Veterans aged 60-69 years. Our innovative neuroimaging and behavioral testing methods will elucidate the abnormalities in auditory cortex that underlie the impaired speech processing of older subjects with and without hearing loss. Moreover, they will permit more refined studies of the abnormalities of auditory cortex in other common disorders (e.g., TBI, schizophrenia, tinnitus, and dementia) in which auditory cortex plays a central role.