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: 9766414
• 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 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9766414
• 关键词: Alzheimer' s Disease; 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 主要进行性失语症（PPA）是一种临床综合征，其特征是孤立的，进行性逐渐丧失 语音和语言能力。 PPA发生在额颞叶的病理和分子变化时 变性（FTLD）或阿尔茨海默氏病（AD）有选择地损害大脑的特定损害语言网络。 PPA中脑萎缩的分布和语言缺陷的模式存在很大的差异 相应地不同。特别是，已经确定了三种PPA的临床变体：i）徽标变体（LVPPA） 与语音能力的丧失有关，剩下的颞叶萎缩和最常见的AD病理学； ii） 具有运动语音和语法缺陷的非流量/农业变体（NFVPPA） 通常是FTLD病理学；和iii）语义变体（SVPPA），概念知识丧失，前方 时间损害，并且最常患有FTLD型病理学。这种分类大大改善了PPA 诊断但临床异质性仍然是一个问题，即使在每个变体中，各个患者的不同 其特定萎缩，语言缺陷和病理学的特定模式的术语。在疾病的早期阶段， LVPPA和NFVPPA之间的鉴别诊断尤其具有挑战性，因为两者都可能发生语音错误 条件和萎缩可能最初是微妙的。 为了更好地区分PPA变体，在这笔赠款中，我们建议检查中的神经振荡 PPA使用磁脑摄影（MEGI）的高时间分辨率大脑成像。我们将检查 与其他任何成像无与伦比的精确性交谈相关的区域神经振荡活动 方式。 MEGI数据将与详细的认知和语言测试，MRI和MRI和 用淀粉样蛋白结合示踪剂PIB生物标志物进行AD的分子PET成像，我们将在我们所有的所有 主题。具体目的是： 1。确定频率特异性静止状态振荡活动和功能的差异模式 PPA变体早期的连接性 2。在PPA变体中的语音反馈处理过程中检查皮质振荡网络活动 3。检查PPA变体的顺序语音产生期间的皮质振荡网络活动 总体而言，我们的发现将使我们能够确定大脑的最早功能表现 PPA中的网络功能障碍，导致有用的生物标志物检测和纵向 评估PPA的渐进性语音下降。