Structural and Effective Connectivity of Reorganized Language Networks in Aphasia

项目摘要 失语症影响约三分之一的中风幸存者，并持续约15 个人，导致衰弱，终身障碍的功能性沟通和严重削弱 生活质量研究表明，尽管有持续的缺陷，慢性失语症（PWA）患者可以 在语言治疗后表现出改善的语言技能以及伴随的神经生理学变化。 然而，对治疗的反应是可变的，目前没有办法预测PWA的程度。 可以恢复。失语症预后难以预测的一个原因是， 语言的神经重组尚不清楚。具体来说，最佳语言恢复与以下因素有关： 激活左半球（LH）组织，但特定的区域，推动改善性能和 它们介导的认知功能（即，特定语言与通用领域过程）是未知的。甚至 关于右半球（RH）在重组中的作用了解较少。一些证据表明 RH的语言活动是不适应的，而其他研究结果表明，RH的招聘是必不可少的，当LH病变 或严重失语时。这种传统的LH与RH的争论似乎过于简单化了一个复杂的 问题.另一个中心假设是，语言重组涉及到 在解剖学上分离但功能上和 在结构上连接语言特异性和一般领域的大脑区域。这一假设将得到检验 通过两个具体目标。第一，有效的连接性（其反映了激活区域的因果影响 在其他区域上）的两个相关语言任务的双侧大脑网络（即，图片命名与语义 特征验证）将通过动态因果模型（DCM）在45名PWA和35名年龄匹配的 对照我们将检验这一假设，即这两种任务中最活跃的中枢和调节区域将是 用于PWA的左额中回（LMFG）和语言特异性左额下回（LIFG） 对于控制，PWA的最佳拟合大脑模型将包括比最佳更强的半球间相互作用， 在控制中拟合模型。其次，我们将研究PWA的语言网络结构完整性 和基于任务的连接预测他们的语言能力。我们将测试假设，更有效的， 双侧网络中前部区域的结构连通性预测更好的语言能力， 仅RH内连接的较强连接性将预示较差的性能。通过实现这些 目的，这个项目将促进我们对语言的有益神经重组的本质的理解， 中风引起的慢性失语症最终，这些发现可以纳入未来的工作，以改善我们的 PWA长期恢复和治疗反应的说明。

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.