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

 描述(申请人提供)：我们存在的一个基本方面是，口语是我们与他人交流的主要手段。不幸的是，中风后，说话的能力，特别是多词(即短语和句子)的产生受到了损害。目前尚不清楚是什么推动了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，通过在中风后72小时内(急性期)以及中风后1、6和12个月再次测试患者，来了解多词产生及其支持的神经结构在康复期间是如何变化的。之前的神经成像和神经心理学研究，包括我们实验室的几项研究，已经发现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。这些能力是在词汇选择过程中解决来自单词竞争对手的干扰的能力，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支持。然而，关于这些能力的作用的结论是从中风发病后的几个月和几年的慢性中风病例中收集的数据得出的。因此，关于大脑-行为关系的结论是有问题的，因为在康复过程中发生了重大的功能重组。由于对慢性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受损对多词产生的影响。此外，选择和工作记忆容量相互作用以支持多词产生的方式仍有待研究。我们将使用最新的纵向数据分析(潜伏期变化评分模型)和结构神经成像(评估灰质损伤和低灌注度以及白质轨迹完整性的序列和建模方法)来验证选择、工作记忆和相关脑区对恢复多词产生至关重要的假设。目的1将通过在重组发生之前，即中风急性期，包括病变较小的患者，对患者进行评估，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。目标2将确定在目标1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个月中风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中风后语言结果至关重要的假设。如果成功，这项研究将导致 详细阐述了多词产生的认知脑基础。这一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的后果至关重要。

 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.