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

失语症中语言和领域通用多需求系统的功能重组

• 批准号: 9888346
• 负责人: Evelina Fedorenko
• 金额: $ 62.42万
• 依托单位: BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9888346
• 关键词: Accounting; Acute; Adopted; Adult; Affect; Age; Alzheimer' s Disease; Anatomy; Aphasia; Aphasia Tests; Architecture; Behavior; Behavioral; Bilateral; Brain; Brain region; Chiroptera; Chronic; Clinical; Cognition; Cognitive; Complex; Data; Data Set; Development; Functional Magnetic Resonance Imaging; Health; Individual; Individual Differences; Intervention; Language; Left; Lesion; Life; Linguistics; Link; Location; Malignant Neoplasms; Measures; Mediating; Methodology; Neuronal Plasticity; Outcome; Parietal; Parietal Lobe; Participant; Patients; Performance; Persons; Phenotype; Play; Process; Property; Recovery; Recovery of Function; Role; Services; Site; Stimulus; Stroke; System; Time; Validation; Work; aging population; aphasia recovery; base; behavior test; cognitive performance; comparison group; effective intervention; effective therapy; frontal lobe; hemisphere damage; improved; individualized medicine; innovation; language comprehension; language impairment; language processing; novel; patient subsets; post stroke; preference; recruit; relating to nervous system; response; stroke incidence; stroke patient; stroke survivor; support network; tool

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.

项目摘要 大约三分之一的中风幸存者患有失语症（Berthier，2005），其中 30% 至 43% 从长远来看，仍然受到严重影响（例如（Bakheit 等，2007）。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变得越来越重要。一个 因此，了解可塑性和恢复背后的大脑机制至关重要。然而， 鉴于中风后的语言障碍和恢复受到许多因素的影响，要解决的问题绝非微不足道。 因素包括脑组织的病前差异、病变的大小和部位以及中风后的行为。 在拟议的工作中，我们检查了能够促进语言恢复的大脑区域。尽管 普遍的假设是语言恢复是由额颞叶网络区域介导的 – 无论是同病左半球（LH）区域还是同源右半球（RH）区域，我们 检查一个新的假设，即域通用额顶多需求（MD）网络也可能 介导失语症患者的语言恢复（PWA）。我们建议评估三个可能的变化 MD 和语言网络的功能架构：（i）在 语言处理； (ii) MD区域之间和语言区域之间的网络内同步；和 (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的特征 通过比较 40 名慢性 PWA 和 40 名年龄匹配的对照组，了解每项指标的差异。然后，我们将识别 神经特征的个体差异与标准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 40 个 PWA 的子集在两个时间点进行了测试，包括功能磁共振成像和行为任务。 这项工作具有创新性，因为它使用了一套方法工具来促进本地化语言处理 在 PWA 中，通过考虑病变部位、体积和解剖功能映射的变异性。进一步，我们检查 两个时间点的患者子集，允许对 MD 网络的变化进行组内比较 时间并作为恢复的函数。该项目的一个关键成果是开发了一个全面的 解释失语症的神经可塑性和语言功能重组机制。其他 该项目的成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，同时考虑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 利用 MD 网络参与语言恢复服务。建立 可能招募非语言区域（即多个需求区域）来服务于语言恢复 对于促进失语症的语言恢复具有深远的影响。