Impact of vestibular loss on central vestibular pathways in aging adults

前庭丧失对老年人中枢前庭通路的影响

• 批准号: 10487441
• 负责人: Yuri Agrawal
• 金额: $ 40.94万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-15 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10487441
• 关键词: Accounting; Adult; Aging; Alzheimer' s Disease; Animal Model; Anterior; Arithmetic; Atrophic; Baltimore; Basal Ganglia; Biomedical Engineering; Brain; Brain region; Cell Nucleus; Clinical; Clinical Skills; Cognitive; Complex; Data; Dorsal; Elderly; Equilibrium; Gait; Grant; Hippocampus (Brain); Human; Image Analysis; Impaired cognition; Individual; Infrastructure; Intervention; Labyrinth; Link; Longitudinal Studies; Magnetic Resonance Imaging; Measures; Mediating; Modeling; Motion Perception; Motor; Motor Cortex; Names; National Institute on Deafness and Other Communication Disorders; Neuraxis; Parietal; Pathway interactions; Performance; Peripheral; Physiology; Pilot Projects; Posture; Prefrontal Cortex; Public Health; Reflex action; Research; Sensory; Signal Transduction; Somatosensory Cortex; Structure; System; Techniques; Thalamic structure; Time; Ventral Lateral Thalamic Nucleus; Ventral Posterior Nucleus; Vestibular loss; Vestibular nucleus structure; age related; analysis pipeline; animal data; behavior measurement; cognitive ability; cognitive process; cognitive skill; computer infrastructure; emerging adult; executive function; healthy aging; imaging facilities; imaging science; neurocognitive test; neuroimaging; novel; prevent; putamen; sensory system; shape analysis; skills; spatial memory; vestibular pathway; way finding

Emerging research is providing compelling evidence that the vestibular system contributes not only to basic reflexes (e.g. vestibulo-ocular, postural) but also to complex cognitive processes including spatial memory and navigation; self-motion perception and motor planning; and executive function. Vestibular function declines with healthy aging, and studies from our group and others have shown that vestibular loss in aging adults is associated with known age-related reductions in cognitive skills including spatial memory and navigation ability, and self-motion perception and motor planning. In a pilot study supported by the NIDCD, we found that older adults with vestibular loss had reduced hippocampal volumes, as well as atrophy of subfields of the thalamus and the basal ganglia. During this pilot study, our group built a pipeline for analysis of neuroimaging data from the Baltimore Longitudinal Study of Aging (BLSA) at the Center for Imaging Science (CIS) in the Johns Hopkins Department of Biomedical Engineering. We established the computational infrastructure for both volumetric analysis and shape analysis. In this proposal, we seek to leverage this infrastructure to more comprehensively investigate the impact of aging on three core central vestibular pathways, and examine the link between structural changes in these pathways and functional changes in clinical skills mediated by these pathways. Specifically, we aim to: Aim 1 Investigate the relationship between peripheral vestibular sensory loss associated with aging and the structure of central vestibular pathways, specifically considering 3 primary central vestibular pathways: 1) spatial cognitive; 2) sensorimotor; 3) prefrontal cortex (executive function). Aim 2 Examine the longitudinal relationships between peripheral vestibular loss and structural changes in central vestibular pathways using longitudinal models and also the novel change-point model in aging adults. Aim 3 Explore the association between structural changes in central vestibular pathways and clinical functional changes cross-sectionally and longitudinally. This proposal represents a unique opportunity to leverage strengths in vestibular physiology and computational neuroimaging to increase our fundamental understanding of the impact of healthy aging on central vestibular networks, and associated clinical consequences. Findings from this study will be used to drive further critical research questions, including 1) Does vestibular loss contribute to the accelerated decline in cognitive ability and brain structure that occurs in individuals with cognitive impairment and Alzheimer’s disease; and 2) Can vestibular interventions for vestibular loss prevent/mitigate changes in central vestibular pathways?

新兴的研究提供了令人信服的证据，表明前庭系统不仅有助于基本的 反射（例如前庭眼反射、姿势反射），也包括复杂的认知过程，包括空间记忆 和导航;自我运动感知和运动规划;和执行功能。前庭功能 随着健康的老龄化而下降，我们小组和其他人的研究表明， 成年人与已知的与年龄相关的认知技能下降有关，包括空间记忆和 导航能力，自我运动感知和运动规划。在国家防治荒漠化和干旱研究所支持的一项试点研究中， 我们发现，前庭功能丧失的老年人海马体积减少， 丘脑和基底神经节的亚区。在这项试点研究中，我们的团队建立了一个分析管道， 来自巴尔的摩老龄化纵向研究（BLSA）的神经成像数据 科学（CIS）在约翰霍普金斯生物医学工程系。我们成立了 用于体积分析和形状分析的计算基础设施。在本建议中，我们力求 利用这一基础设施，更全面地调查老龄化对三个核心中心的影响， 前庭通路，并检查这些通路的结构变化和功能之间的联系 这些途径介导的临床技能的变化。具体而言，我们的目标是：目标1调查 与年龄相关的外周前庭感觉丧失与中枢神经系统结构的关系 前庭通路，特别考虑3个主要的中枢前庭通路：1）空间认知; 2） 感觉运动; 3）前额叶皮层（执行功能）。目标2：检查纵向关系 外周前庭损失和中央前庭通路结构变化之间的纵向关系 模型，也是新的变点模型在老年人。目标3：探索 中枢前庭通路的结构变化和横截面的临床功能变化， 纵向。这一建议代表了一个独特的机会，利用优势，前庭生理学 和计算神经成像来增加我们对健康老龄化影响的基本理解 对中枢前庭网络的影响以及相关的临床后果。这项研究的结果将用于 推动进一步的关键研究问题，包括1）前庭损失是否有助于加速 认知能力和大脑结构下降，发生在认知障碍的个体中， 阿尔茨海默病; 2）前庭功能丧失的前庭干预能否预防/减轻阿尔茨海默病的变化？ 中枢前庭通路