Investigating the role of bvFTD-affected networks in socioemotional behavior

摘要 行为变异型额颞叶痴呆(Bvftd)是为数不多的几种神经综合征之一。 对他们来说，最初的临床诊断完全依赖于对患者的社交和情感症状的评估。 直到最近，还没有对社会情绪行为的测量在神经退行性疾病中得到心理测量的验证。 疾病患者。在最初的四年里，这个项目直接解决了这个问题，成功地 制定这样的措施，其中一部分已经纳入FTD测试模块 由国家老年病研究所通过国家阿尔茨海默病协调中心推动。现在 这些测试已经被开发出来，我们希望用它们来模拟人类背后的神经系统 健康和疾病状态下的社会情绪行为。这项建议是建立在最近的发现基础上的 每种主要的神经退行性疾病最初都以一个独特的内在联系的功能网络为目标 (ICN)在大脑中。其中三个ICN已被确定为不同临床表现的最初功能障碍部位 BvFTD的亚型：腹侧显著网络(SN)、任务控制网络(TCN)和语义网络 情景网络(SCN)。尽管如此，人们对这些ICN驱动的具体社会情感行为知之甚少， 无论是在正常认知中还是在疾病中。通过确定这些测试如何反映网络连通性，我们可以使用 他们可以更容易地筛查患者的早期bvFTD，测量症状进展，并更好地预测 患者潜在的神经病理学。本项目的具体目标是阐明这些项目的贡献 三种神经网络对bvFTD的正常社会行为和社会情绪症状的影响：目标1： 阐明bvFTD的三个网络如何与健康人的社会情绪行为和认知相对应 正常的成年人。我们将收集40名年轻对照组的静息状态磁共振成像(RsMRI)和社会测试数据 (20-45岁)，与第一阶段从健康的老年对照组(45-90岁)收集的数据一起 这个项目的。我们假设，内脏情绪反应性测量的分数与SN相关 连通性；社交自控力将与TCN连通性相关；以及需要应用社会情绪的任务 知识将与SCN连接相关联。目标2：确定这三个网络与 BvFTD患者社会功能障碍的严重程度。我们将收集50名bvFTD患者的rsMRI和社交数据， 当添加到本项目第一阶段收集的数据时，将提供足够的动力来 调查患者的社会情绪症状与网络功能障碍之间的对应关系。目标 3：研究bvFTD早期出现的社会情绪和网络功能障碍。为 这个更具探索性的目标是，我们将每年从30名症状前期的队列中收集rsMRI和社会数据。 来自导致FTD基因突变的家族的携带者(PC)和30名非携带者(NONC)，以检查模式 在后来发展为行为表型的PC中，社会情绪功能的进行性变化，以及 识别PC中与三个ICN中连接性改变相对应的社会情绪变化。

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.