TMS as a Biomarker of Plasticity in Aphasia Recovery

描述(申请人提供)：本申请的中心目标是探索经颅磁刺激(TMS)作为评估语言系统神经可塑性的潜在工具，并探索该技术作为中风后失语症患者功能恢复的生物标志物的应用。失语症影响了大约三分之一的急性中风患者，是一种常见的、往往是破坏性的永久性残疾来源。失语症的长期康复是高度可变的，人们认为这在很大程度上取决于大脑对语言处理的可塑性重组的潜力。然而，到目前为止，还没有神经可塑性的生理学指标被纳入中风后失语患者的评估中。TMS是一种非侵入性脑刺激形式，已被用于诱导包括语言处理在内的神经功能的局部可逆变化。TMS的行为和神经生理效应反映了大脑皮层的反应性，并受到公认的可塑性机制的驱动。因此，这些效应可能被用作大脑中神经再生能力的指标。这项拟议项目的第一个具体目标是确定TMS引起的命名成绩变化是否与慢性失语症的长期康复相关。在建立了一个预测慢性失语症严重程度的统计模型后，我们将从操作上定义语言可塑性的差异，即患者的表现是比模型所解释的更好(高可塑性)还是更差(低可塑性)。使用类似于我们已经证明的TMS方案可以瞬时地促进慢性非流利性失语症患者的命名能力；我们预测 在高可塑性受试组中，短暂性TMS诱导的命名增强作用将比低可塑性受试组更大。拟议项目的第二个具体目标是确定是否可以使用一种灵敏的运动生理学TMS测量来评估慢性非流利性失语患者的可塑性。为了实现这一目标，我们将再次使用我们的失语症康复统计模型来确定语言可塑性高的患者在运动生理指标上是否比可塑性低的患者表现出更大的影响。最终目的将探索在亚急性中风和失语症患者中采用这些TMS措施的可行性，并将确定这些措施在这些患者群体中是否可靠和可靠。该项目目标的实现将极大地扩展对语言系统可塑性本质的认识。重要的是，语言可塑性标记物的发展也将为更好地预测失语症结果、更适当地对治疗性语言干预进行分层以及进一步开发旨在促进语言系统适应性变化的治疗方法奠定基础。

DESCRIPTION (provided by applicant): The central objective of this application is to explore trans- cranial magnetic stimulation (TMS) as a potential tool for assessing neuroplasticity in the language system, and to explore the utility of this technology as a biomarker for functional recovery in patients with aphasia after stroke. Aphasia affects approximately one third of acute stroke patients and is a common and often devastating source of persistent disability. Long-term aphasia recovery is highly variable and is understood to depend largely on the brain's potential for plastic reorganization of language processing. However, to date, no physiologic measures of neuroplasticity have been incorporated into the assessment of patients with post- stroke aphasia. TMS is a form of noninvasive brain stimulation that has been used to induce focal reversible changes in neural function, including language processing. The behavioral and neurophysiologic effects of TMS reflect the responsiveness of the cortex and are driven by well-recognized mechanisms of plasticity. These effects could therefore potentially be employed as indices of the neuroplastic capacity in the brain. The first specific aim of the proposed project i to determine whether TMS-induced changes in naming performance correlate with long-term recovery from chronic aphasia. Having developed a statistical model that predicts chronic aphasia severity, we will operationally define differences in language plasticity in terms of whether patients perform better than accounted for by the model (high plasticity) or worse (low plasticity). Using a TMS protocol similar to one that we have already shown can transiently facilitate naming ability in patients with chronic nonfluent aphasia; we predict that the degree of transient TMS-induced enhancement in naming will be greater in the high plasticity group of subjects than in the low plasticity group. The second specific aim of the proposed project is to determine whether a sensitive TMS measure of motor physiology can be employed to assess plasticity in patients with chronic nonfluent aphasia. To achieve this aim, we will again employ our statistical model of aphasia recovery to determine whether patients with high language plasticity exhibit a greater effect of TMS on measures of motor physiology than low plasticity patients. The final aim will explore of the feasibility of employing these TMS measures in patients with sub-acute stroke and aphasia, and will determine whether these measures are robust and reliable in this patient population. Achievement of the aims of this project will greatl expand knowledge about the nature of plasticity in language systems. Importantly, development of a marker of language plasticity will also lay the foundation for improved prognostication of aphasia outcomes, more appropriate stratification of therapeutic language interventions, and the further development of treatments aimed at facilitating adaptive change in language systems.