Investigating the role of bvFTD-affected networks in socioemotional behavior

摘要 额颞叶痴呆的行为变异（bvFTD）是少数神经系统综合征之一 对他们来说，最初的临床诊断完全依赖于对患者社交和情绪症状的评估。 直到最近，没有社会情绪行为的措施在神经退行性疾病中得到心理测量学的验证。 疾病患者。在最初的四年里，该项目成功地直接解决了这一问题， 开发此类措施，其中一部分已纳入FTD测试模块 由国家老龄化研究所通过国家阿尔茨海默病协调中心推广。现在 这些测试已经开发出来，我们希望用它们来模拟人类的神经系统。 健康和疾病状态下的社会情绪行为。这一建议是基于最近的发现， 每种主要的神经退行性疾病最初都针对一种独特的内在连接的功能网络， (ICN)在大脑中。这些ICN中的三个已经被确定为不同临床中功能障碍的初始部位。 bvFTD的亚型：腹侧突显网络（SN），任务控制网络（TCN）和语义- 上下文网络（SCN）。尽管如此，人们对这些ICN驱动的特定社会情感行为知之甚少， 无论是在正常认知还是在疾病中。通过确定这些测试如何反映网络连接，我们可以使用 更容易筛查患者的早期bvFTD，测量症状进展， 患者潜在的神经病理学该项目的具体目标是阐明这些贡献 三个神经网络与正常社会行为和bvFTD的社会情绪症状：AIM 1： 阐明三个bvFTD网络如何对应于健康人群的社会情绪行为和认知， 正常的成年人我们将从40名年轻对照组中收集静息态MRI（rsMRI）和社会测试数据 (ages 20-45），其与在第一阶段期间从健康老年对照（年龄45-90）收集的数据一起 of this project项目.我们假设，内脏情绪反应的测量分数将与SN相关， 连接;社会自我控制将与TCN连接相关;以及需要应用社会情感的任务 知识将与SCN连通性相关。目标2：确定这三个网络与 bvFTD中社交功能障碍的严重程度。我们将收集50例bvFTD患者的rsMRI和社会数据， 当将其添加到本项目第一阶段收集的数据中时，将提供足够的电力， 探讨患者的社会情绪症状与网络功能障碍之间的对应关系。目的 3：检查bvFTD早期发生的社会情绪和网络功能障碍。为 这个更具探索性的目标，我们将每年从30名症状前患者的队列中收集rsMRI和社会数据， 携带者（PC）和30名非携带者（NONC）来自家庭与FTD引起的基因突变，以检查模式 在后来发展出行为表型的PC中，社会情感功能发生了渐进性变化， 识别与三个ICN中的连接改变相对应的PC中的社会情绪变化。

ABSTRACT The behavioral variant of frontotemporal dementia (bvFTD) is one of only a handful of neurologic syndromes for whom initial clinical diagnosis relies entirely on assessment of patients' social and emotional symptoms. Until recently, no measures of socioemotional behavior were psychometrically validated in neurodegenerative disease patients. In its first four years, this project has directly addressed this problem by successfully developing such measures, a subset of which have already been incorporated into an FTD testing module promoted by National Institute of Aging through the National Alzheimer's Disease Coordinating Centers. Now that these tests have been developed, we hope to use them to model the neural systems underlying human socioemotional behavior in both healthy and disease states. This proposal builds on the recent discovery that each major neurodegenerative disorders initially targets a distinctive intrinsically connected functional network (ICN) in the brain. Three of these ICNs have been identified as the initial site of dysfunction in different clinical subtypes of bvFTD: the ventral salience network (SN), the task control network (TCN), and the semantic- context network (SCN). Still, little is known about the specific socioemotional behaviors driven by these ICNs, either in normal cognition or in disease. By identifying how these tests reflect network connectivity, we can use them to more easily screen patients for early bvFTD, measure symptom progression, and better predict patients' underlying neuropathology. The Specific Aims of this project are to elucidate the contribution of these three neural networks to normal social behavior and to the socioemotional symptoms of bvFTD: AIM 1: To clarify how the three bvFTD networks correspond to socioemotional behavior and cognition in healthy normal adults. We will collect resting-state MRI (rsMRI) and social testing data from 40 younger controls (ages 20-45), which together with data collected from healthy older controls (ages 45-90) during the first phase of this project. We hypothesize that scores on measures of visceral emotional reactivity will correlate with SN connectivity; social self-control will correlate with TCN connectivity; and tasks requiring applied socioemotional knowledge will correlate with SCN connectivity. AIM 2: To determine how these three networks relate to severity of social dysfunction in bvFTD. We will collect rsMRI and social data from 50 bvFTD patients, which when added to data collected during the first phase of this project, will provide adequate power to investigate the correspondence between patients' socioemotional symptoms and network dysfunction. AIM 3: To examine socioemotional and network dysfunction occurring at the earliest stage of bvFTD. For this more exploratory aim, we will collect rsMRI and social data yearly from a cohort of 30 presymptomatic carriers (PC) and 30 non-carriers (NONC) from families with FTD-causing gene mutations, to examine patterns of progressive change in socioemotional function in PCs who later develop a behavioral phenotype, and identify socioemotional changes in PCs that correspond to altered connectivity in the three ICNs.