Primary Progressive Aphasia: Neural Bases and Rehabilitation

描述（由申请人提供）：原发性进行性失语症（PPA）是由影响语言皮层的神经退行性疾病导致的语言技能逐渐下降。文献中已经描述了PPA患者口语和书面语言障碍的典型模式（Gorno-Tempini等人，2004；Hodges等人，1992；Neary等人，1998）；然而，特定语言领域缺陷的神经和认知基础是一个值得进一步研究的领域。此外，PPA患者目前没有得到包括语言病理学家在内的临床专业人员的推荐和服务。事实上，行为治疗在PPA中观察到的语言障碍的效用尚未得到系统的探索。这个为期三年的项目的长期目标是描述PPA患者语言能力下降的认知和神经解剖学基础，并检查每种PPA变体的语言治疗效用。具体来说，该项目旨在探索PPA中灰质和白质异常与关键语言域损伤之间的关系；评估理论动机行为治疗对词汇检索障碍患者的效用；并检查对语言治疗反应的解剖学和行为学预测。为了实现这些目标，将对30名PPA患者和30名正常对照者进行全面的语言测试，包括语法、语义、音韵学和正字法方面的测试。基于体素的形态测量（VBM）和弥散张量成像（DTI）将用于评估区域灰质萎缩和白质束完整性，这些成像测量将与复合语言测量相关联。此外，每个PPA诊断变体中的5名患者将接受一种独特的治疗方案，该方案旨在利用未被保留的认知过程，同时试图纠正和/或补偿受损的认知过程。每个PPA变体对行为治疗的反应将通过检查训练和未训练项目和任务的表现以及评估结构化治疗完成后的维持情况来表征。最后，治疗前灰质和白质完整性的测量以及复合语言测量的表现模式将被检查相对于对治疗的反应。这些分析将为PPA患者的神经解剖损伤与其语言特征和对行为治疗的反应能力之间的关系提供重要证据。

DESCRIPTION (provided by applicant): Primary progressive aphasia (PPA) is a gradual decline in language skills that results from neurodegenerative disease affecting language cortex. The typical patterns of spoken and written language impairments in individuals with PPA have been characterized in the literature (Gorno-Tempini et al., 2004; Hodges et al., 1992; Neary et al., 1998); however, the neural and cognitive bases for deficits in specific language domains are an area that warrants further investigation. In addition, individuals with PPA are currently under-referred and underserved by clinical professionals, including speech-language pathologists. In fact, the utility of behavioral treatment for the language impairments observed in PPA has yet to be systematically explored. The long-term goals of this three-year project are to characterize the cognitive and neuro anatomical bases for language decline in individuals with PPA and also to examine the utility of language treatment in each of the PPA variants. Specifically, the project aims to explore the relation between gray and white matter abnormalities and impairment to critical language domains in PPA; to assess the utility of theoretically motivated behavioral treatment for lexical retrieval in individuals with the disorder; and to examine anatomical and behavioral predictors of response to language treatment. In order to accomplish these aims, 30 individuals with PPA and 30 normal controls will be administered a comprehensive language battery comprising tests in the domains of syntax, semantics, phonology, and orthography. Voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) will be used to evaluate regional gray matter atrophy and white matter tract integrity and these imaging measures will be correlated with composite language measures. In addition, five individuals in each diagnostic variant of PPA will be administered a unique treatment protocol designed to capitalize on spared cognitive processes while attempting to remediate and/or compensate for impaired processes. Response to behavioral treatment in each PPA variant will be characterized by examining performance on trained and untrained items and tasks and by assessing maintenance following completion of structured treatment. Finally, pre-treatment measures of gray and white matter integrity as well as patterns of performance on composite language measures will be examined relative to response to treatment. These analyses will provide important evidence regarding the relation between neuro anatomical damage in PPA patients and their language characteristics and ability to respond to behavioral treatment.