Anatomical Physiology of Semantic Associations in Primary Progressive Aphasia

描述(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的萎缩可以影响到颞鞘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。无名症，即不能给物体命名，是PPA的常见症状。命名需要物体知识、单词知识的完整性，以及这两个领域的互动联系，即语音编码和发音。这项研究的目标是更好地理解PPA中命名损伤的机制，作为初步步骤[这可能会导致神经可塑性诱导治疗，如经颅磁刺激。]在以前的研究中，我们使用被称为事件相关电位(ERPs)的脑电反应来探测通常仅基于行为无法观察到的细微加工异常。在对物体图片-视觉单词对的反应中，N400事件相关电位揭示了单词被预测和预测性编码的程度。来自患者的ERP没有区分物体的名称和相关的单词(狗-猫)，这表明未能从一般的单词识别进行到特定的水平。N400对相关单词的反应减少与左前颞叶(ATL)萎缩相关。对物体图片对的反应是正常的，这表明单词而不是物体加工过程中存在障碍。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-客体测试不需要。在这项建议中，我们通过检查跨模式的视觉-听觉交互作用(具体目标1)来解决这种潜在的困惑。在一项测试中，视觉对象将与听觉单词配对。我们预测，即使在这种交叉模式设计中，PPA患者也会在ERPs和行为方面表现出从一般到特定的加工障碍。在第二个测试中，视觉物体之后是听觉物体声音(狗叫声)。我们预测PPA患者将表现出视觉对象-听觉对象关系的正常分化，这表明即使在跨通道对象-对象关联仍然可以被唤起的情况下，也会发生异常。我们还将检验单词专一性的ERP指数是否与左侧ATL萎缩相关(特定目标2)，以展示该区域在听觉和视觉单词的关联联系中的作用。 最后，在这项建议中，我们结合了一种融合的方法来研究PPA的生理学：MRI静息状态功能连通性分析(特定目标3)。[我们将检查语言网络中ATL与其他震中中心之间的连接在PPA中是否异常，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.]