Language in Primary Progressive Aphasia

描述(申请人提供)：原发性进行性失语症(PPA)是一种脑部疾病，会导致词语使用和理解的逐渐和日益衰弱的损害。尽管PPA越来越多地被认识到，但在研究和患者服务方面，它仍然没有得到充分的服务。这项申请寻求继续资助一个项目，该项目是西北大学综合PPA研究计划的核心。我们的目标是最大限度地利用项目头5年招募的独特队列，并招募新患者进行假设驱动的命名、单词理解、附带记忆和句子处理调查，这些新任务是由一个多学科调查团队设计的，他们在PPA方面有密切合作和高生产率的记录。我们相信，这种类型的研究计划可以在多学科方法的结构内最好地实现，例如我们为此目的而建立的方法，由神经成像(Emily Rogalski博士)、神经语言学(Cynthia Thompson博士)、事件相关电位(Ken Paller博士)、神经心理学(Sandra WeIntrub博士)、神经行为学(Marsel Mesulam博士)、生物统计学(Alfred Rademaker博士)和磁共振物理学(Todd Parrish博士)的研究人员领导。对于下一个周期，我们选择了具体的目标来解决这个项目的四个核心主题：PPA的亚型和时间演变，命名和语义扭曲的机制，流利性和语法能力的特征，以及从患者峰值萎缩部位的分布推断的语言的解剖基础。在这一框架内，我们的主要目标将是1.完成对选定的当前参与者子集的纵向研究，以描绘PPA的自然过程并表征其初始阶段的演变(实验1)。2用跨通道事件相关电位实验(实验2)来阐明失调症的机制。3.采用事件相关电位和眼动记录的方法(实验3和实验4)，考察在线任务下动词和句子加工的动态扰动。4.确定PPA中特定材料和通道的学习扭曲的解剖学基础(实验5)。5.促进通过《美国复苏和再投资法案》(ARRA)启动的国际PPA连接网站(IMPPACT)的持续发展，将其作为一个国际合作患者和资源登记处(ppaconConnection.org)。

DESCRIPTION (provided by applicant): Primary progressive aphasia (PPA) is a brain disease that causes a gradual and increasingly more debilitating impairment of word usage and comprehension. Although it is being recognized with increasing frequency, PPA remains underserved with respect to research and patient services. This application seeks continued funding for a project that is the centerpiece of a comprehensive PPA Research Program at Northwestern University. The goal is to make maximal use of a unique cohort that has been recruited during the first 5 years of the project and to enroll new patients for hypothesis-driven investigations of naming, word comprehension, incidental memory and sentence processing with novel tasks designed by a multidisciplinary team of investigators with a track record of close collaboration and high productivity in PPA. We believe that this type of research program can best be achieved within the structure of a multidisciplinary approach such as the one we have established for this purpose, led by researchers in neuroimaging (Dr. Emily Rogalski), neurolinguistics (Dr. Cynthia Thompson), event-related potentials (Dr. Ken Paller), neuropsychology (Dr. Sandra Weintraub), neurobehavior (Dr. Marsel Mesulam), biostatistics (Dr. Alfred Rademaker) and Magnetic Resonance physics (Dr. Todd Parrish). For the next cycle, we chose specific aims that address the four core themes of this project: subtyping and temporal evolution of PPA, mechanisms of naming and semantic distortions, characteristics of fluency and grammatical competence, and anatomical substrates of language as inferred from the distribution of peak atrophy sites in patients. Within this framework, our primary aims will be 1. To complete a longitudinal study of a select subset of current participants in order to delineat the natural course of PPA and to characterize the evolution of its initial stages (Experiment 1). 2 To clarify the mechanisms of anomia with a cross-modal ERP experiment (Experiment 2). 3. To investigate dynamic perturbations of verb and sentence processing with on-line tasks using the methodology of ERP and eye movement recording (Experiments 3 and 4). 4. To identify the anatomical basis of material- and modality-specific distortions of learning in PPA (Experiment 5). 5. To foster the continued development of the International PPA Connection (IMPPACT) website, launched through the American Recovery and Reinvestment Act (ARRA), as an international collaborative patient and resource registry (ppaconnection.org).