Functional reorganization of the language and domain-general multiple demand systems in aphasia

项目摘要 失语症影响了大约三分之一的中风幸存者(Berthier，2005)，其中30%到43% 从长期来看仍然受到严重影响(例如Bakheit等人，2007年)。随着中风负担的增加，它是 为失语症患者开发有效和个性化的治疗方法日益重要。一个 因此，了解构成可塑性和恢复的大脑机制是至关重要的。然而， 考虑到中风后的语言障碍和恢复受到许多因素的影响，需要解决的问题远非微不足道 这些因素包括发病前脑组织的差异、病变的大小和位置以及中风后的行为。 在这项拟议的工作中，我们研究了能够辅助语言恢复的大脑区域。而当 普遍的假设是，语言恢复是由额叶-时间网络的区域调节的-- 无论是单侧的左半球区域还是相应的右半球区域，我们 检验一种新的假设，即全域性额顶多需求(MD)网络也可以 失语症患者语言恢复的介导性研究。我们建议评估以下三个可能的变化 MD和语言网络的功能架构：(I)各网络在下列期间的反应幅度 语言处理；(2)MD区域之间和语言区域之间的网络内同步；以及 (3)MD和语言区域之间的跨网络同步。我们将首先描述中风后的特征 通过比较40名慢性PWA和40名年龄匹配的对照组，每项指标的差异。然后，我们将确定 神经特征的个体差异与标准语言表现的差异 行为测试。最后，我们将评估MD网络对语言恢复的因果贡献 在两个时间点测试了40个PWA的子集，这两个时间点都是在fMRI和行为任务中。 这项工作是创新的，因为它使用了一套方法论工具来促进本地化语言处理 在PWA中，通过考虑病变部位、体积和解剖-功能标测的可变性。此外，我们还研究了 两个时间点的患者子集，允许在组内比较MD网络在 时间和作为恢复的函数。该项目的一个关键成果是开发了一个全面的 失语症神经可塑性和语言功能重组机制的解释。另一个 该项目的结果是描绘了神经表型--包括急性期--这解释了 PWA的语言和认知表现的可变性，同时解释了解剖功能的可变性 映射。第三个重要成果将是为新的行为和神经刺激疗法铺平道路。 这利用了MD网络在语言恢复服务方面的参与。建立 可能征聘非语言区域(即多个需求区域)，以提供语言恢复服务 对促进失语症患者的语言恢复有着深远的意义。

PROJECT ABSTRACT Aphasia affects approximately one third of stroke survivors (Berthier, 2005), and between 30 and 43% of these remain severely affected in the long term (e.g. (Bakheit et al., 2007). With a rising burden of stroke, it is increasingly important to develop effective and individualized treatment for patients with aphasia. An understanding of the brain mechanisms that underlie plasticity and recovery is therefore essential. However, the problem to solve is far from trivial given that language impairment and recovery after stroke is impacted by many factors including premorbid differences in brain organization, size and site of lesion, and post-stroke behaviors. In the proposed work, we examine the brain regions that are capable of subserving language recovery. While the prevailing hypothesis is that language recovery is mediated by the regions of the fronto-temporal network – either the ipsilesional left-hemisphere (LH) regions or the homologous right-hemisphere (RH) regions, we examine a novel hypothesis that a domain-general fronto-parietal multiple demand (MD) network may also mediate language recovery in patients with aphasia (PWA). We propose to evaluate three possible changes in the functional architecture of the MD and language networks: (i) response magnitude in each network during language processing; (ii) intra-network synchronization among MD regions, and among language regions; and (iii) across-network synchronization between MD and language regions. We will first characterize post-stroke differences in each measure by comparing 40 chronic PWA and 40 age-matched controls. Then, we will identify individual differences in neural signatures that co-vary with differences in language performance on standard behavioral tests. Finally, we will assess the causal contribution of the MD network to language recovery in a subset of 40 PWA tested at two time points, both in fMRI and behavioral tasks. This work is innovative because it uses a suite of methodological tools to facilitate localize language processing in PWA by accounting for variability in lesion site, volume and anatomy-function mapping. Further, we examine a subset of patients at two time points, allowing a within group comparison of changes in the MD network over time and as a function of recovery. A key outcome of this project is the development of a comprehensive explanation for mechanisms of neuroplasticity and reorganization of language function in aphasia. Another outcome of the project is the delineation of neural phenotypes – including in the acute stage – that explain the variability in linguistic and cognitive performance of PWA while accounting for variability in anatomy-function mapping. A third important outcome will be to pave the way for new behavioral and neuro-stimulation therapies that capitalize on the engagement of the MD network in the service of language recovery. Establishing the potential recruitment of non-language regions (i.e., multiple demand regions) in the service of language recovery has profound implications for facilitating language recovery in aphasia.