Structural and Effective Connectivity of Reorganized Language Networks in Aphasia

项目总结 失语症影响大约三分之一的中风幸存者，并在其中约15%持续存在 个体，导致衰弱的、终生的功能沟通障碍，严重削弱 生活质量。研究表明，尽管慢性失语症(PWA)患者持续存在缺陷，但 在语言治疗后表现出改善的语言技能和伴随的神经生理学变化。 然而，对治疗的反应是可变的，目前还没有办法预测PWA的程度 可能会康复。很难预测失语症结果的一个原因是， 语言的神经重组尚不清楚。具体地说，最佳的语言恢复与 左半球(LH)组织中的激活，但驱动性能改善和 它们所调节的认知功能(即，特定于语言的过程与特定于领域的过程)是未知的。连 关于右脑(RH)在重组中的作用，人们知之甚少。一些证据表明 RH对语言的活动是不适应的，而其他研究结果表明，当LH损害时，RH募集是必不可少的 体型大或失语症严重时。这种传统的LH和RH之争似乎过于简单化了一个复杂的 有问题。这项研究的另一种中心假设是，语言重组涉及 在解剖隔离的但在功能和功能上的双侧网络内的完整组织的动态招募 结构上连接的语言特定的和领域通用的大脑区域。这一假设将得到检验。 通过两个具体目标。第一，有效连通性(反映激活区域的因果影响 关于两个相关语言任务(即，图片命名和语义任务)的双边大脑网络 特征验证)将通过动态因果建模(DCM)在45名PWA和35名年龄匹配的PWA中进行检查 控制。我们将测试这两个任务中最活跃的中枢和调节区的假设 PWA的全域性左额中回(LMFG)和特定语言的左额下回(LIFG) 对于对照，PWA的最佳大脑模型将包括比最佳大脑模型更强的半球间相互作用- 使模型适合控件。第二，我们将检查PWAS的语言网络结构完整性的程度 而基于任务的连接性预测了他们的语言能力。我们将检验这样一种假设，即更有效和 双边网络中前部区域的结构连通性预示着更好的语言能力，而 只有RH内连接的更强连接将预示着性能较差。通过实现这些 目的，这个项目将增进我们对语言有益神经重组的本质的理解 中风引起的慢性失语症。最终，这些发现可以被纳入未来的工作中，以改善我们的 PWA患者远期康复和治疗反应的预测。

PROJECT SUMMARY Aphasia affects approximately one-third of stroke survivors and persists in about 15% of these individuals, resulting in debilitating, life-long impairments in functional communication and severely diminished quality of life. Research has shown that despite persistent deficits, persons with chronic aphasia (PWA) can demonstrate improved language skills with concomitant neurophysiological changes following language therapy. However, response to treatment is variable and there is currently no way to predict the degree to which PWA may recover. One reason for the difficulty in predicting aphasia outcomes is that the mechanisms of beneficial neural reorganization of language are unclear. Specifically, optimal language recovery has been linked to activation in left hemisphere (LH) tissue, yet the specific regions that drive improved performance and the cognitive functions they mediate (i.e., language-specific versus domain-general processes) are unknown. Even less is understood regarding the role of the right hemisphere (RH) in reorganization. Some evidence suggests RH activity for language is maladaptive while other findings indicate RH recruitment is essential when LH lesions are large or when aphasia is severe. This traditional LH versus RH debate appears to oversimplify a complex problem. The alternative, central hypothesis of the proposed research is that language reorganization involves the dynamic recruitment of intact tissue within a bilateral network of anatomically-segregated but functionally and structurally connected language-specific and domain-general brain regions. This hypothesis will be tested through two specific aims. First, effective connectivity (which reflects the causal influence of activated regions on other areas) of a bilateral brain network for two related language tasks (i.e., picture naming and semantic feature verification) will be examined via Dynamic Causal Modeling (DCM) in 45 PWA and 35 age-matched controls. We will test the hypothesis that the most active hubs and modulatory regions for both tasks will be domain-general left middle frontal gyrus (LMFG) for PWA and language-specific left inferior frontal gyrus (LIFG) for controls and that best-fit brain models for PWA will include stronger inter-hemispheric interactions than best- fit models in controls. Second, we will examine the extent to which PWAs’ language network structural integrity and task-based connectivity predict their language abilities. We will test the hypothesis that greater effective and structural connectivity of anterior regions within the bilateral network predict better language abilities while stronger connectivity of only intra-RH connections will be predictive of poor performance. By achieving these aims, this project will advance our understanding of the nature of beneficial neural reorganization of language in stroke-induced chronic aphasia. Ultimately, such findings can be incorporated into future work to improve our prognostication of long-term recovery and response to therapy in PWA.