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实用性。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、经常是破坏性的持续性残疾的来源。长期失语症的恢复是高度可变的，并且被认为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指标被纳入卒中后失语症患者的评估中。经颅磁刺激是一种非侵入性脑刺激，已被用于诱导神经功能的局部可逆变化，包括语言处理。经颅磁刺激的行为和神经生理效应反映了皮层的反应性，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的指标。拟议项目的第一个具体目标是确定tms诱导的命名性能变化是否与慢性失语症的长期恢复相关。在开发了一个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。使用类似于我们已经证明的TMS方案可以暂时促进慢性非流利性失语症患者的命名能力；我们预测的程度

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.