Memory and Aging Center, Department of Neurology, University of California, San Francisco, CA 94158, USA.
Department of Communication Sciences and Disorders, University of Texas, Austin, USA.
Neuroimage Clin. 2019;22:101797. doi: 10.1016/j.nicl.2019.101797. Epub 2019 Mar 27.
The semantic variant of primary progressive aphasia (svPPA) is a clinical syndrome characterized by semantic memory deficits with relatively preserved motor speech, syntax, and phonology. There is consistent evidence linking focal neurodegeneration of the anterior temporal lobes (ATL) to the semantic deficits observed in svPPA. Less is known about large-scale functional connectivity changes in this syndrome, particularly regarding the interplay between affected and spared language networks that leads to the unique cognitive dissociations typical of svPPA. Using whole-brain, seed-based connectivity on task-free Magnetic Resonance Imaging (MRI) data, we studied connectivity of networks anchored to three left-hemisphere regions crucially involved in svPPA symptomatology: ATL just posterior to the main atrophic area, opercular inferior frontal gyrus, and posterior inferior temporal lobe. First, in 32 healthy controls, these seeds isolated three networks: a ventral semantic network involving anterior middle temporal and angular gyri, a dorsal articulatory-phonological system involving inferior frontal and supramarginal regions, and a third functional connection between posterior inferior temporal and intraparietal regions likely involved in linking visual and linguistic processes. We then compared connectivity strength of these three networks between 16 svPPA patients and the 32 controls. In svPPA, decreased functional connectivity in the ventral semantic network correlated with weak semantic skills, while connectivity of the network seeded from the posterior inferior temporal lobe, though not significantly different between the two groups, correlated with pseudoword reading skills. Increased connectivity between the inferior frontal gyrus and the superior portion of the angular gyrus suggested possible adaptive changes. Our findings have two main implications. First, they support a functional subdivision of the left IPL based on its connectivity to specific language-related regions. Second, the unique neuroanatomical and linguistic profile observed in svPPA provides a compelling model for the functional interplay of these networks, being either up- or down- regulated in response to disease.
原发性进行性失语症（PPA）的语义变体是一种临床综合征，其特征是语义记忆缺陷，运动言语、句法和语音相对保留。有一致的证据将前颞叶（ATL）的局灶性神经退行性变与 svPPA 中观察到的语义缺陷联系起来。对于这种综合征中的大规模功能连接变化，人们知之甚少，特别是关于导致 svPPA 特有的认知分离的受影响和未受影响的语言网络之间相互作用的知识。我们使用任务无关的磁共振成像（MRI）数据的全脑种子连接，研究了三个左半球区域锚定的网络的连接性，这些区域对 svPPA 症状学至关重要：ATL 就在主要萎缩区域的后部、外侧额下回和后部下颞叶。首先，在 32 名健康对照者中，这些种子分离出三个网络：一个涉及前中颞叶和角回的腹侧语义网络、一个涉及下额回和缘上回的背侧发音语音系统，以及一个可能涉及视觉和语言过程连接的后下颞叶和顶内区域之间的第三个功能连接。然后，我们比较了 16 名 svPPA 患者和 32 名对照者这三个网络的连接强度。在 svPPA 中，腹侧语义网络的功能连接减少与语义技能较弱相关，而来自后下颞叶种子的网络的连接性虽然在两组之间没有显著差异，但与假词阅读技能相关。额下回和角回上部之间连接性的增加表明可能存在适应性变化。我们的发现有两个主要的含义。首先，它们支持基于与特定语言相关区域的连接性对 IPL 进行功能细分。其次，svPPA 中观察到的独特神经解剖学和语言学特征为这些网络的功能相互作用提供了一个令人信服的模型，即根据疾病的情况进行上调或下调。
