Investigating the role of bvFTD-affected networks in socioemotional behavior

描述（由申请人提供）：额颞叶痴呆的行为变体（bvFTD）是少数几种神经系统综合征之一，其初步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患者中进行心理测量验证。在最初的四年里，该项目通过成功开发此类措施直接解决了这一问题，其中一部分已被纳入国家老龄化研究所通过国家阿尔茨海默病协调中心推广的FTD测试模块。现在这些测试已经开发出来，我们希望用它们来模拟健康和疾病状态下人类社会情绪行为的神经系统。这一建议建立在最近的发现基础上，即每种主要的神经退行性疾病最初都针对大脑中独特的内在连接功能网络（ICN）。其中3个ICN已被确定为bvFTD不同临床亚型功能障碍的初始部位：腹侧显著性网络（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驱动的特定社会情绪行为知之甚少，无论是在正常认知还是疾病中。通过确定这些测试如何反映网络连接，我们可以使用它们更容易地筛查患者的早期bvFTD，测量症状进展，并更好地预测患者的潜在神经病理学。本项目的具体目的是阐明这三种神经网络对正常社会行为和bvFTD社会情绪症状的贡献：目的1：阐明三种bvFTD网络如何对应于健康正常成人的社会情绪行为和认知。我们将收集40名年轻对照组（年龄20-45岁）的静息态MRI（rsMRI）和社会测试数据，以及在本项目第一阶段从健康老年对照组（年龄45-90岁）收集的数据。我们假设，内脏情绪反应的测量分数将与SN连接相关;社会自我控制将与TCN连接相关;需要应用社会情绪知识的任务将与SCN连接相关。目的2：确定这三个网络与bvFTD中社交功能障碍严重程度的关系。我们将从50例bvFTD患者中收集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，将提供足够的把握度来研究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：研究bvFTD早期发生的社会情感和网络功能障碍。为了这个更具探索性的目标，我们将每年从一个由30名前驱症状携带者（PC）和30名非携带者（NONC）组成的队列中收集rsMRI和社会数据，这些携带者来自具有导致FTD的基因突变的家庭，以检查后来发展为行为表型的PC中社会情绪功能的渐进性变化模式，并确定与三个ICN中改变的连接相对应的PC中的社会情绪变化。

DESCRIPTION (provided by applicant): 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.