Brain Health and Aphasia Recovery

摘要 失语症患者的语言障碍可能有很大差异。我们的神经生物学 基于脑卒中损害的模型只能部分解释失语症状。我们假设 中风损伤外的残留脑组织的完整性是一个重要的，但尚未完全认识到， 失语症严重程度和恢复的决定因素。 众所周知，心血管危险因素会导致累积性广泛脑损伤 小血管疾病（SVD）在失语症文献之外，SVD与 认知储备差，对各种形式的神经损伤的弹性降低。中风幸存者， 失语症通常具有心血管危险因素，并且通常表现出SVD。然而， 在我们的恢复模型中通常不考虑SVD，即使残留的脑组织是 负责克服功能丧失。因此，病变外的SVD程度较高， 导致更严重的失语症症状和更少的恢复机会，由于减少的能力，以弥补 中风损伤我们的目标是直接测试这个假设。 我们建议评估失语症是如何形成的中风病变结合残留的大脑 完整神经影像学（脑部MRI）非常适合解决这个问题。SVD由以下部分组成 微血管病性缺血性变化和微血管病变。SVD引起的缺血性变化可能是 使用T2加权和T2-FLAIR图像通过白色高信号测量， 微血管造影可以使用可测量性加权图像来评估。SVD优先影响白色 物质和扩散MRI可以提供白色物质微结构完整性及其 与整个大脑神经元网络结构（大脑连接体）的关系。 利用我们在卒中后病变症状标测、白色物质和连接体成像方面的经验 我们提出了一个全面的研究神经生物学和影响SVD在失语症。我们的项目将建立在 SVD评估的国际指南（报告血管变化的标准， nEuroimaging - STRIVE），并将开发一种创新的多模式机器学习方法，以充分 评估大脑的完整性 将在慢性（项目1）和急性的背景下评估大脑完整性和语言测量 （2）失语症的康复。行为和语言评估将由项目4指导。与 神经影像学核心，我们将开发和分发多模式神经影像学方法，以量化严重程度 以及SVD的位置 具体目标1将纵向评估SVD的独立影响，控制脑病变， 急性和慢性症状，以及急性和慢性语言恢复。第2章评价 通过评估SVD和中风的影响，研究SVD导致语言障碍的机制 连接体神经网络结构的损伤，联合长距离白色纤维的丢失及其 与语义、词汇语义、词汇语音、语音/语音缺陷的关系。

Abstract Language impairments can vary considerably between individuals with aphasia. Our neurobiological models based on the stroke lesion can only partly explain the aphasic symptoms. We hypothesize that the integrity of the residual brain tissue outside the stroke lesion is an important, but not yet fully appreciated, determinant of aphasia severity and recovery. It is well recognized that cardiovascular risk factors lead to cumulative widespread brain damage through small vessel disease (SVD). Outside the aphasia literature, SVD has been strongly associated with poor cognitive reserve and reduced resiliency to various forms of neurological injury. Stroke survivors with aphasia typically have cardiovascular risk factors and they commonly exhibit SVD. However, the impact of SVD is not usually taken into account in our models of recovery, even though the residual brain tissue is responsible for overcoming the loss of function. It follows that higher degrees of SVD outside the lesion may lead to worse aphasic symptoms and less chances of recovery due to reduced capacity to compensate for the stroke injury. Our goal is to directly test this hypothesis. We propose to evaluate how aphasia is shaped by the stroke lesion in combination with residual brain integrity. Neuroimaging (brain MRI) is ideally suited to address this problem. SVD is composed of microangiopathic ischemic changes and microhemorrhages. The ischemic changes from SVD can be measured through white matter hyper intensities using T2-weighted and T2-FLAIR images, and the microhemorrhages can be assessed using susceptibility-weighted images. SVD preferentially affects white matter and diffusion MRI can provide additional measures of white matter microstructural integrity and their relationship with the whole brain neuronal networks architecture (the brain connectome). Using our experience with post-stroke lesion symptom mapping, white matter and connectome imaging we propose a comprehensive study of the neurobiology and impact of SVD in aphasia. Our project will build on international guidelines for SVD assessment (The STandards for ReportIng Vascular changes on nEuroimaging - STRIVE) and it will develop an innovative multimodal machine learning approach to fully assess brain integrity. Brain integrity and language measures will be assessed in the context of chronic (Project 1) and acute (Project 2) aphasia recovery. The behavioral and linguistic assessments will be guided by Project 4. With the neuroimaging core, we will develop and distribute a multimodal neuroimaging approach to quantify the severity and location of SVD. Specific Aim 1 will longitudinally assess the independent impact of SVD, controlling for the brain lesion, on acute and chronic symptoms, as well as acute and chronic language recovery. Specific Aim 2 will evaluate the mechanisms by which SVD leads to language impairments by assessing the impact of SVD and stroke lesions on connectome neural network architecture, loss of associative long-range white matter fibers and its relationship with semantic, lexical-semantic, lexical-phonological, phonological/phonetic deficits.