The effects of aging and hearing loss on human auditory cortex

描述（由申请人提供）： 人类听觉皮层（HAC）是一个复杂的区域，包含多个功能特化的听觉皮层场（ACFs）。阐明ACF的组织结构和功能特性对于理解声音感知的皮层机制是必要的。我们提出了四个实验来阐明人类ACF的结构和功能组织，并表征其解剖结构和功能特性的变化所造成的老化和感音神经性听力损失（SNHL）。将研究三组受试者：（1）听力正常的年轻受试者;（2）听力正常的老年受试者;和（3）轻度至中度双侧感音神经性听力损失（SNHL）的老年受试者。每个实验组将参与四个实验。 在前一个授予期间，我们分析了人类ACFs的音调组织，以揭示人类ACFs的组织计划。HAC具有与其他灵长类物种相似的组织：它包含12个ACF，其中3个具有tonotopically组织的核心ACF，被7个带和2个parabelt ACF包围。在Exp. 1，我们将使用最先进的MRI扫描仪复制和扩展这些发现。我们将从年轻的受试者的数据和评估年龄和SNHL相关的变化，ACF音调组织，强度功能，频率调谐带宽，空间调谐和注意力调制。语音处理受到年龄的影响，特别是与SNHL相关。我们以前发现，外侧带ACFs专门用于处理语音，而内侧带ACFs专门用于处理复杂的非语音刺激。在Exp. 2，我们将映射激活所产生的口语音节和各种控制刺激，以阐明语音处理专门化的横向ACFs。我们还将测量由于衰老和SNHL引起的言语刺激激活模式的变化。以前的研究和我们实验室的试验数据表明，HAC解剖结构的年龄相关变化，并表明它们与听觉感知能力相关。我们已经开发了一些创新的技术来定量分析大脑皮层的解剖结构。在Exp. 3，我们将使用这些技术来表征年龄和SNHL相关的改变在HAC通过测量皮质厚度和组织特性，反映树突密度，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言语理解测试，并发现这些能力会因衰老而受损，特别是在SNHL患者中。在Exp. 4，我们将使用这些和其他测试来量化三个受试者组的听觉感知能力。结果将与实验中观察到的功能激活模式相关。1和2中测量的HAC解剖结构，并与Exp. 3.意义与听力损失有关的言语理解障碍是有听力损失和没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相关的言语感知障碍的解剖学和功能基础。此外，它将提供必要的规范性数据，将澄清HAC的基本解剖和功能组织。这些结果将提高HAC神经影像学研究的精度，HAC与各种听力学，神经学和精神病学疾病有关，包括耳鸣，中风，痴呆，自闭症，精神分裂症和创伤性脑损伤（TBI）。

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).