TMS as a Biomarker of Plasticity in Aphasia Recovery

描述（由申请人提供）：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效用。失语症影响大约三分之一的急性中风患者，是持续性残疾的常见且往往具有毁灭性的原因。长期失语症的恢复情况变化很大，并且被认为很大程度上取决于大脑对语言处理进行可塑性重组的潜力。然而，迄今为止，尚未将神经可塑性的生理测量纳入对中风后失语症患者的评估中。 TMS 是一种非侵入性脑刺激，已被用来诱导神经功能（包括语言处理）的局部可逆变化。 TMS 的行为和神经生理学效应反映了皮质的反应性，并由公认的可塑性机制驱动。因此，这些效应可能被用作大脑神经可塑性能力的指标。该项目的第一个具体目标是确定 TMS 引起的命名表现变化是否与慢性失语症的长期恢复相关。在开发出预测慢性失语症严重程度的统计模型后，我们将根据患者的表现是否优于模型（高可塑性）或更差（低可塑性）来定义语言可塑性的差异。使用与我们已经展示的类似的 TMS 方案可以暂时提高慢性非流利性失语症患者的命名能力；我们预测的程度 短暂的 TMS 引起的命名增强在高可塑性组中比在低可塑性组中更大。该项目的第二个具体目标是确定运动生理学的敏感 TMS 测量是否可用于评估慢性非流利性失语症患者的可塑性。为了实现这一目标，我们将再次采用失语症恢复统计模型来确定语言可塑性高的患者是否比语言可塑性低的患者表现出更大的 TMS 对运动生理学测量的影响。最终目标将探讨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该患者群体中是否稳健可靠。该项目目标的实现将极大地扩展关于语言系统可塑性本质的知识。重要的是，语言可塑性标志物的开发也将为改善失语症结果的预测、更合适的语言治疗干预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.