Longitudinal multi-modality imaging in progressive apraxia of speech (Diversity Supplement)

项目总结 进行性言语失用症是一种神经退行性言语运动计划障碍，影响 演讲的产生。在R01的第一个周期中，我们演示了进行性语言失用症 与大脑灰质和白质的进行性退化有关的，伴有变性 从一个相对集中的起点扩散到整个大脑，我们展示了区域变化 与临床下降相关。然而，这些结构变化背后的神经生物学机制 疾病的进展仍然难以捉摸，代表着知识上的差距。了解疾病 机制将对开发适当的治疗方法和评估 治疗。因此，我们第二周期的主要目标是利用先进的神经成像技术来 评估进行性语言失用症疾病进展的神经生物学机制。这个 这项研究的第一个目标是确定tau摄取的区域分布和渐进性扩散。 Tau正电子发射体层成像。第二个目标是使用静息状态和基于任务的功能磁共振和 扩散张量束成像，以表征功能和结构连通性的中断 跨大脑网络随着时间的推移而发展，以及这些变化如何与区域tau摄取相关。我们最后一次 目的是研究这些神经影像指标与临床疾病的相关性。 进步。为了实现这些目标，我们将招募50名进行性言语失用患者，并 每名患者将每隔一年接受两次连续评估。在每一次评估中，患者将有一个 神经学和言语语言评估，使用[18F]AV-1451配体和3T的tau-PET扫描 磁共振成像扫描，将包括静息状态功能MRI和扩散张量成像 序列。一部分患者还将接受基于任务的短时间fMRI扫描，以允许我们评估大脑 与语音清晰度相关的活动。我们的分析将评估这些模式中的异常 运动语言网络的区域，特别是运动前和运动皮质，并决定如何功能障碍 在这个网络内随着时间的推移而变化，以及疾病是否传播到其他网络。我们会 在一组标准的感兴趣区域中计算tau-PET摄取量，然后测量结构和 这些感兴趣区域之间的功能连接。这种方法将使我们能够评估多式联运 并确定这些不同的疾病机制如何相互联系以及 临床表现下降。这种机械性的方法将增加我们对疾病进展和 进行性语言失用的病理过程与脑连通性的关系 可能有助于提高诊断特异性并将对未来发展至关重要的知识 机械疗法。

PROJECT SUMMARY Progressive apraxia of speech is a neurodegenerative speech motor planning disorder that affects the production of speech. In the 1st cycle of the R01 we demonstrated that progressive apraxia of speech is associated with progressive degeneration of both the grey and white matter of the brain, with degeneration spreading throughout the brain from a relatively focal starting point, and we showed that regional changes correlated to clinical decline. However, the neurobiological mechanisms underlying these structural changes and disease progression remain elusive and represent a gap in knowledge. Understanding disease mechanisms will be critical for the development of appropriate therapies and for assessing the efficacy of treatments. The primary goal of our 2nd cycle is, therefore, to utilize advanced neuroimaging techniques to assess the neurobiological mechanisms underlying disease progression in progressive apraxia of speech. The first objective of the study is to determine the regional distribution and progressive spread of tau uptake using tau PET imaging. The second objective is then to using resting-state and task-based functional MRI and diffusion tensor tractography to characterize how disruptions in functional and structural connectivity within and across brain networks progress over time, and how these changes are related to regional tau uptake. Our last objective is then to investigate correlations between these neuroimaging measures and clinical disease progression. To accomplish these aims we will recruit 50 patients with progressive apraxia of speech, and each patient will undergo two serial assessments one year apart. At each assessment, patients will have a neurological and speech-language assessment, tau-PET scan using the [18F]AV-1451 ligand and a 3T magnetic resonance imaging scan that will include resting-state functional MRI and diffusion tensor imaging sequences. A subset of patients will also undergo a short task-based fMRI scan to allow us to assess brain activity related to speech articulation. Our analysis will assess abnormalities in these modalities within the motor speech network of regions, particularly premotor and motor cortex, and determine how dysfunction within this network changes over time and whether the disease spreads to involve other networks. We will calculate tau-PET uptake in a standard set of regions-of-interest and then measure both structural and functional connectivity between these regions-of-interest. This approach will allow us to assess multi-modal correlations and determine how these different disease mechanisms are related to each other as well as clinical decline. This mechanistic approach will increase our understanding of disease progression and the relationship between pathological processes and brain connectivity in progressive apraxia of speech; knowledge that may help improve diagnostic specificity and will be critical for the future development of mechanistically based therapies.