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

项目摘要 失语症影响大约三分之一的中风幸存者（Berthier，2005），其中30%至43%的人患有失语症。 在长期内仍然受到严重影响（例如（Bakhman et al.，2007年）。随着中风负担的增加， 为失语症患者开发有效的个体化治疗方法越来越重要。一个 因此，了解大脑可塑性和恢复的机制是至关重要的。但 要解决的问题远非微不足道，因为中风后的语言障碍和恢复受到许多因素的影响， 这些因素包括发病前脑组织的差异、病变的大小和部位以及中风后的行为。 在拟议的工作中，我们研究了能够促进语言恢复的大脑区域。而 流行的假设是语言恢复是由额颞叶网络区域介导的， 无论是同病灶左半球（LH）区域还是同源右半球（RH）区域，我们 研究一个新的假设，即一个域一般额顶叶多需求（MD）网络也可能 失语症患者的语言恢复（PWA）。我们建议评估三种可能的变化， MD和语言网络的功能架构：（i）在每个网络中的响应幅度， （ii）MD区域之间以及语言区域之间的网络内同步;以及 (iii)MD和语言区域之间的跨网络同步。我们将首先描述中风后 通过比较40例慢性PWA和40例年龄匹配的对照组，研究了每项指标的差异。然后，我们将确定 神经信号的个体差异与语言表现的差异共同变化， 行为测试最后，我们将评估MD网络对语言恢复的因果贡献， 在两个时间点测试的40个PWA的子集，无论是在功能磁共振成像和行为任务。 这项工作是创新的，因为它使用了一套方法工具，以促进本地化的语言处理 通过考虑病变部位、体积和解剖结构-功能映射的变异性，在PWA中。此外，我们检查 两个时间点的患者子集，允许在组内比较MD网络的变化， 时间和恢复的函数。该项目的一个主要成果是制定了一个全面的 解释失语症的神经可塑性和语言功能重组的机制。另一 该项目的成果是描绘神经表型-包括在急性期-解释了 PWA的语言和认知表现的变异性，同时考虑解剖功能的变异性 映射.第三个重要成果将为新的行为和神经刺激疗法铺平道路 利用MD网络参与语言恢复服务。建立 非语言区域的潜在招聘（即，多个需求区域）提供语言恢复服务 对促进失语症的语言恢复具有深远的意义。

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.