Dynamic Brain Imaging of Speech in Primary Progressive Aphasia

原发性进行性失语症言语的动态脑成像

• 批准号: 10237347
• 负责人: MARIA LUISA GORNO TEMPINI
• 金额: $ 56.23万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-15 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10237347
• 关键词: Alzheimer' s Disease; Alzheimer' s disease pathology; Alzheimer’s disease biomarker; Amyloid; Anterior; Atrophic; Behavioral; Binding; Biological Assay; Biological Markers; Brain; Brain imaging; Classification; Clinical; Data; Development; Differential Diagnosis; Disease; Dorsal; Feedback; Frequencies; Frontotemporal Lobar Degenerations; Goals; Grant; Image; Inferior; Knowledge; Language; Language Disorders; Language Pathology; Language Tests; Left; Magnetic Resonance Imaging; Magnetoencephalography; Measures; Methodology; Methods; Molecular; Motor; Neuronal Dysfunction; Neurosciences; Parietal; Pathologic; Pathology; Patients; Pattern; Performance; Positron-Emission Tomography; Preparation; Primary Progressive Aphasia; Production; Reproduction; Rest; Semantics; Short-Term Memory; Speech; Syndrome; Time; Tracer; Variant; cerebral atrophy; clinical Diagnosis; clinical heterogeneity; cognitive testing; diagnostic biomarker; imaging biomarker; imaging modality; improved; individual patient; motor control; nervous system disorder; network dysfunction; phonology; rehearsal; relating to nervous system; response; temporal measurement

Project Summary Primary progressive aphasia (PPA) is a clinical syndrome characterized by isolated, progressive loss of speech and language abilities. PPA occurs when pathological and molecular changes of frontotemporal lobar degeneration (FTLD) or Alzheimer's disease (AD) selectively damage language-specific networks of the brain. There is considerable variability in the distribution of brain atrophy in PPA, and patterns of language deficits vary accordingly. In particular, three clinical variants of PPA have been identified: i) logopenic variant (lvPPA) associated with loss of phonological abilities, left temporal-parietal atrophy and most often AD pathology; ii) nonfluent/agrammatic variant (nfvPPA) with motor speech and grammar deficits, left inferior frontal damage and often FTLD pathology; and iii) semantic variant (svPPA), with loss of conceptual knowledge, anterior temporal damage and also most often with FTLD-type pathology. This classification has greatly improved PPA diagnosis but clinical heterogeneity remains an issue, even within each variant, as individual patients differ in terms of their specific patterns of atrophy, language deficits and pathology. In the early stages of the disease, differential diagnosis between lvPPA and nfvPPA is particularly challenging as speech errors can occur in both conditions and atrophy might initially be subtle. To better distinguish between PPA variants, in this grant, we propose to examine neural oscillations in PPA using high temporal resolution brain imaging with magnetoencephalography (MEGI). We will examine regional neural oscillatory activity associated with speaking with a precision unmatched by any other imaging modality. MEGI data will be examined in conjunction with detailed cognitive and language testing, MRI and molecular PET imaging with the amyloid binding tracer PIB biomarker for AD that will be available in all our subjects. The specific aims are: 1. To identify differential patterns of frequency-specific resting-state oscillatory activity and functional connectivity in early stages of PPA variants 2. To examine cortical oscillatory network activity during speech feedback processing in PPA variants 3. To examine cortical oscillatory network activity during sequential speech production in PPA variants Overall, our findings will enable us to identify some of the earliest functional manifestations of brain network dysfunction in PPA, leading to the development of useful biomarkers to detect and longitudinally assess the progressive speech decline in PPA.

项目摘要 原发性进行性失语（PPA）是一种临床综合征，其特征是孤立的、进行性的失语症。 言语和语言能力。PPA发生于额颞叶的病理和分子改变， 痴呆症（FTLD）或阿尔茨海默病（AD）选择性地损害大脑的语言特异性网络。 PPA患者脑萎缩的分布和语言缺陷的模式存在相当大的差异。 相应地变化。特别地，已经鉴定了PPA的三种临床变体： 与语音能力丧失、左侧颞顶叶萎缩和最常见的AD病理相关; ii） 不流利/语法缺失变体（nfvPPA）伴运动性语言和语法缺陷，左下额叶损伤 和通常FTLD病理;和iii）语义变体（svPPA），丧失概念知识，前 颞叶损伤，也最常伴有FTLD型病理。这种分类大大提高了PPA 诊断，但临床异质性仍然是一个问题，即使在每一个变种，因为个别患者不同， 他们的萎缩，语言缺陷和病理学的具体模式。在疾病的早期阶段， lvPPA和nfvPPA之间的鉴别诊断特别具有挑战性，因为在两种情况下都可能发生语音错误。 条件和萎缩最初可能是微妙的。 为了更好地区分PPA变体，在这项资助中，我们建议检查神经振荡， PPA使用高时间分辨率脑成像与脑磁图（MEGI）。我们将研究 与说话相关的区域神经振荡活动，其精确度是任何其他成像都无法比拟的 模态。MEGI数据将与详细的认知和语言测试、MRI和 分子PET成像与淀粉样蛋白结合示踪剂PIB生物标志物的AD，将可在我们所有的 科目具体目标是： 1.识别频率特异性静息态振荡活动的差异模式和功能 PPA变体早期阶段的连通性 2.检查PPA变体在语音反馈处理过程中的皮层振荡网络活动 3.检查PPA变体在顺序言语产生过程中的皮层振荡网络活动 总的来说，我们的研究结果将使我们能够确定一些最早的大脑功能表现， PPA的网络功能障碍，导致有用的生物标志物的发展，以检测和纵向 评估PPA的进行性言语衰退。