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.

项目概要 原发性进行性失语症 (PPA) 是一种临床综合征，其特征是孤立的、进行性丧失语言能力。 言语和语言能力。当额颞叶发生病理和分子变化时就会发生PPA 退化（FTLD）或阿尔茨海默病（AD）选择性地损害大脑的语言特定网络。 PPA 中脑萎缩的分布以及语言缺陷的模式存在相当大的变异性 相应地有所不同。特别是，已经确定了 PPA 的三种临床变体： i) 日志减少变体 (lvPPA) 与语音能力丧失、左颞顶叶萎缩以及最常见的 AD 病理有关；二） 不流利/语法错误变异（nfvPPA），伴有运动言语和语法缺陷，左下额叶损伤 常常是 FTLD 病理； iii）语义变体（svPPA），概念知识丢失，前 颞叶损伤，最常见的是 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，即使在每个变体中，因为个体患者的差异 就其特定的萎缩模式、语言缺陷和病理学而言。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，因为两者都可能出现语音错误 状况和萎缩最初可能是微妙的。 为了更好地区分 PPA 变体，在本次资助中，我们建议检查神经振荡 PPA 使用高时间分辨率脑成像和脑磁图 (MEGI)。我们将检查 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所无法比拟的 情态。 MEGI 数据将与详细的认知和语言测试、MRI 和 使用用于 AD 的淀粉样蛋白结合示踪剂 PIB 生物标志物进行分子 PET 成像，该成像将在我们所有的产品中提供 科目。具体目标是： 1. 识别特定频率的静息态振荡活动和功能的差异模式 PPA 变体早期阶段的连接 2. 检查 PPA 变体语音反馈处理过程中的皮质振荡网络活动 3. 检查 PPA 变体序列语音产生过程中的皮质振荡网络活动 总的来说，我们的发现将使我们能够识别大脑的一些最早的功能表现 PPA 中的网络功能障碍，导致开发有用的生物标志物来检测和纵向 评估 PPA 中的进行性言语衰退。