Language and neural recovery from stroke: Role of selection and working memory

 描述（由申请人提供）：我们存在的一个基本方面是，口语是我们与他人沟通的主要手段。不幸的是，说话的能力，和多词（即，特别是短语和句子）的产生在中风后受损。目前还不清楚是什么驱动中风后语言产生的成功恢复。该提案描述了一项研究计划，该计划使用认知行为测试，神经成像和统计建模来了解多词产生和支持它的神经结构如何在中风后72小时内（急性期）和中风后1个月，6个月和12个月内测试患者恢复期间发生变化。以前的神经影像学和神经心理学研究，包括我们实验室的几项研究，已经确定了两种认知能力和相关的大脑区域，它们可能对多词产生至关重要。这些能力是在单词选择过程中解决来自单词竞争者的干扰的能力，以及在工作记忆中存储语义信息的能力，分别由左额下回的后部和前部区域提供。然而，关于这些能力的作用的结论是从慢性中风病例、中风发作后数月和数年收集的数据中得出的。因此，关于脑-行为关系的结论是有问题的，因为在恢复过程中发生了重大的功能重组。由于对慢性病患者的研究通常排除了语言障碍已经解决的人，他们低估了大脑小区域损伤对多词产生的影响。此外，选择和工作记忆能力相互作用，以支持多词生产的方式仍有待研究。我们将使用纵向数据分析（潜在变化分数模型）和结构神经成像（序列和建模方法，以评估灰质和白色物质轨道的完整性的损伤和灌注不足）的最新创新来测试选择和工作记忆以及相关的大脑区域对多词生产的恢复至关重要的假设。目的1将通过在重组发生之前评估患者来检验选择和语义工作记忆能力对于多词产生是必要的这一假设，即，在急性期，中风后72小时内，这将包括那些较小的病变。目标2将确定目标1中测试的急性中风患者中与选择和工作记忆相关的神经结构。目标3将通过评估急性、1、6和12个月卒中后时间点的行为和神经解剖学变化来检验选择和工作记忆能力的恢复对卒中后语言结果至关重要的假设。如果成功，这项研究将导致 多词产生的大脑认知基础的详细理论。这些知识将具有重要的健康意义，因为有关语言能力如何受损并随后恢复的信息对于通过制定语言康复策略来管理中风后果至关重要。

 DESCRIPTION (provided by applicant): A fundamental aspect of our existence is that spoken language is our primary means of communication with others. Unfortunately, the ability to speak, and multiword (i.e., phrase and sentence) production in particular, is impaired following stroke. It is unclear what drives successful recovery of language production following stroke. The proposal describes a research program that uses cognitive behavioral testing, neuroimaging, and statistical modeling to understand how multiword production and the neural structures that support it change during recovery by testing patients within 72 hours of stroke (acute stage) and again at 1, 6, and 12 months after stroke. Previous neuroimaging and neuropsychological studies, including several from our laboratories, have identified two cognitive abilities and associated brain regions that may be critical for multiword production. These abilities are the ability to resolve interference from word competitors during word selection and the ability to store semantic information in working memory, subserved by posterior and anterior regions of the left inferior frontal gyrus, respectively. However, conclusions about the role of these abilities have been drawn from data collected from chronic stroke cases, months and years following the onset of stroke. As a result, conclusions about brain-behavior relations are problematic due to significant reorganization of function that occurs during recovery. Because studies of chronic patients typically exclude people whose language disorders have resolved, they underestimate the impact of damage to small regions of the brain on multiword production. Further, the way selection and working memory capacities interact to support multiword production remains to be examined. We will use recent innovations in the analysis of longitudinal data (Latent Change Score models) and structural neuroimaging (sequences and modeling approaches to assess damage and hypoperfusion to gray matter and integrity of white matter tracks) to test the hypothesis that selection and working memory and associated brain regions are critical to the recovery of multiword production. Aim 1 will test the hypothesis that selection and semantic working memory capacities are necessary for multiword production by assessing patients before reorganization occurs, i.e., at the acute stage, within 72 hours of stroke, which will include those with smaller lesions. Aim 2 will identify the neural structures associated with selection and working memory in the acute stroke patients tested in Aim 1. Aim 3 will test the hypothesis that recovery of selection and working memory capacities is critical to post stroke language outcome by assessing behavior and neuroanatomical changes across acute, 1, 6, and 12 months post stroke time points. If successful, this research will result in a detailed theory of the cognitive-brain basis of multiword production. This knowledge will have important health implications because information about how language ability is impaired and subsequently recovers is essential for managing the consequences of stroke through the development of language rehabilitation strategies.