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（PPA）。PPA的萎缩可以影响颞叶语言网络内的任何区域，为研究大脑-语言关系提供了独特的机会。命名障碍，无法命名物体，是PPA的常见症状。命名需要对象知识、单词知识的完整性，以及这两个领域、语音编码和发音的相互联系。这项研究的目的是更好地理解PPA中命名损伤的机制，作为可能导致神经可塑性诱导治疗（如经颅磁刺激）的初步步骤。在之前的研究中，我们使用脑电图反应，即事件相关电位（ERPs）来探测通常仅凭行为无法观察到的细微加工异常。N400 erp对物体图像-视觉词对的反应揭示了词被预期和预测编码的程度。来自患者的erp不能区分物体的名称和相关的单词（狗-猫），这表明无法从一般的单词识别到特定的单词识别。N400对相关词汇的反应减少与左颞叶萎缩相关。对物体图片对的反应是正常的，这表明文字处理受损，而不是物体处理受损。在本初步研究中，加工需求并不平衡，客体-词测试需要刺激类型之间的映射，而客体-客体测试不需要。在本提案中，我们通过检查跨模式的视觉-听觉相互作用来解决这种潜在的混淆（具体目标#1）。在一项测试中，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患者也会在erp和行为方面表现出从通用到特定的加工损伤。在第二个测试中，视觉对象之后是听觉对象的声音（狗叫）。我们预测PPA患者将表现出正常的视觉客体-听觉客体关系分化，这表明即使跨模的客体-客体关联仍然可以被唤起，也会出现异常。我们还将研究单词特异性的ERP指数是否与左ATL萎缩相关（Specific Aim #2），以证明该区域在听觉和视觉单词的联想联系中的作用。

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.]