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 失语症影响大约三分之一的中风幸存者（Berthier，2005年），其中30％至43％ 从长远来看（例如（Bakheit等，2007）。 对失语症的患者开发有效和个性化的治疗越来越重要 因此，了解塑料和恢复基础的大脑机制至关重要。 鉴于中风后的语言障碍和恢复受到许多人的影响，要解决的问题是从微不足道的 包括大脑组织中的病前差异，病变的大小和部位以及中风后行为的因素。 在支撑工作中，我们检查了能够在语言恢复时的大脑区域 令人难以置信的假设是语言恢复是由额叶网络的区域介导的 ipsiles左半球区域（LH）区域或同源右半球区域（RH）区域，Wee 研究一个新的假设，即域额叶额叶多重需求（MD）网络也可能 调解失语症患者的语言恢复（PWA）。 MD和语言网络的功能架构：（i）在每个网络中的响应幅度 语言处理； （iii）MD和语言区域之间的跨网络同步。 通过比较40个慢性PWA和40个年龄匹配的对照，我们将确定每个度量的差异。 与标准的语言表现差异的神经信号中的个体差异联系 最终，我们将评估MD网络对语言的因果 在fMRI和行为任务中，在两个时间点测试的40个PWA的子集。 这项工作创新，因为它使用一套方法学工具来促进本地化语言处理 在PWA中，我们检查了病变部位的变异性，数量和解剖功能映射 在两个时间点的一部分患者，可以在整个小组中比较MD网络的变化。 时间和作为恢复的函数。 解释神经片剂的机制和语言功能的重组。 该项目的结果是神经表型的删除 - 包括在急性阶段 - 解释您 PWA语言和认知性能的可变性，同时考虑解剖功能的可变性 映射。 这利用了MD网络的英语在语言恢复服务中。 在语言恢复服务中，非语言区域的潜在招募（即多个需求区域） 对促进失语症的语言恢复具有深远的影响。