Anatomical Physiology of Semantic Associations in Primary Progressive Aphasia

描述（由申请人提供）：由神经退行性疾病引起的语言障碍被称为原发性进行性失语症（PPA）。PPA中的萎缩可以影响颞叶语言网络中的任何区域，为检查大脑-语言关系提供了独特的机会。失名症，即无法命名对象，是PPA中的常见症状。认知需要客体知识、词汇知识的完整性，以及这两个领域（语音编码和发音）的互动联系。这项研究的目的是更好地了解PPA中命名障碍的机制，作为初步步骤[这可能导致神经可塑性诱导治疗，如经颅磁刺激。在之前的研究中，我们使用了被称为事件相关电位（ERP）的脑电图反应来探测微妙的处理异常，这些异常通常无法单独基于行为来观察。N400事件相关电位在响应对象图片视觉词对揭示了在何种程度上的话已经预期和预测编码。患者的ERPs没有区分对象的名称与相关的单词（狗-猫），这表明未能从通用到特定的单词识别水平。N400对相关词反应的减少与左前颞叶（ATL）的萎缩相关。对物体图片的反应是正常的，这表明损害的话，而不是对象处理。在这项初步研究中，加工需求并不平衡，因为客体-词测试需要刺激类型之间的映射，而客体-客体测试则不需要。在这个提议中，我们通过检查跨通道视听交互来解决这个潜在的混淆（具体目标#1）。在一个测试中，视觉对象将与听觉单词配对。我们预测，即使在这种跨模态设计中，PPA患者也会表现出ERP和行为的一般到特定处理障碍。在第二个测试中，视觉对象将被听觉对象声音（狗叫声）跟随。我们预测，PPA患者将表现出正常的分化的视觉对象-听觉对象的关系，表明即使跨模态的对象-对象的关联，仍然可以诱发命名障碍发生。我们还将研究是否ERP指数的字特异性与左ATL萎缩（具体目标#2），展示了该地区的作用，在听觉和视觉词汇的联想联系。 最后，在本提案中，我们采用了一种收敛方法来研究PPA的生理学：MRI静息状态功能连接分析（具体目标#3）。[We将检查ATL和语言网络中其他震中之间的连接是否在PPA中异常，以及这种异常是否与ERP测试中的表现有关。

DESCRIPTION (provided by applicant): Language disorders caused by neurodegenerative diseases are known as Primary Progressive Aphasias (PPA). Atrophy in PPA can affect any region within the temporosylvian language network, affording unique opportunities for examination of brain-language relationships. Anomia, the inability to name objects, is a common symptom in PPA. Naming requires the integrity of object knowledge, word knowledge, and the interactive linkage of these two domains, phonological encoding, and articulation. The goal of this study is to better understand the mechanisms of naming impairments in PPA, as a preliminary step [that could potentially lead to neuroplasticity-inducing treatments such as transcranial magnetic stimulation.] In prior studies we used electroencephalographic responses, known as event-related potentials (ERPs), to probe for subtle processing abnormalities often unobservable based on behavior alone. N400 ERPs in response to object picture-visual word pairs revealed the extent to which words had been anticipated and predictively coded. ERPs from patients did not differentiate the name of the object from related words (dog-cat), suggesting a failure to proceed from generic to specific levels of word identification. Reductions in N400 responses to related words correlated with atrophy in the left anterior temporal lobe (ATL). Responses to object picture pairs were normal, suggesting impairment in word rather than object processing. Processing demands were not balanced in this preliminary study, as the object-word test required mapping between stimulus types while the object-object test did not. In this proposal we address this potential confound by examining crossmodal visual-auditory interactions (Specific Aim #1). In one test visual objects will be paired with auditory words. We predict that even within this crossmodal design, PPA patients will demonstrate a generic-to-specific processing impairment in ERPs and behavior. In the second test, visual objects will be followed by auditory object sounds (dog-barking). We predict that PPA patients will show normal differentiation of visual object-auditory object relationships, demonstrating that anomia occurs even when crossmodal object-object associations can still be evoked. We will also examine whether an ERP index of word specificity correlates with left ATL atrophy (Specific Aim #2), demonstrating a role of this region in the associative linkage of auditory as well as visual words. Finally, in this proposal we incorporate a convergent method to investigate the physiology of PPA: MRI resting state functional connectivity analysis (Specific Aim #3). [We will examine whether connectivity between ATL and other epicenters in the language network is abnormal in PPA, and whether such abnormalities relate to performance in the ERP test.]