Investigating the role of bvFTD-affected networks in socioemotional behavior

调查受 bvFTD 影响的网络在社会情感行为中的作用

• 批准号: 9040068
• 负责人: Katherine P Rankin
• 金额: $ 43.9万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-15 至 2019-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9040068
• 关键词: Address; Adult; Affect; Age; Aging; Alzheimer' s Disease; Behavior; Behavioral; Biological Neural Networks; Brain; Clinical; Clinical Trials; Cognition; Conscious; Country; Data; Dementia; Disease; Disease model; Emotional; Emotions; Employee Strikes; Family; Foundations; Functional disorder; Gene Mutation; Goals; Health; Human; Impairment; Institutes; Knowledge; Magnetic Resonance Imaging; Measures; Mental disorders; Mind; Modeling; Neurodegenerative Disorders; Neurologic; Patients; Pattern; Phase; Phenotype; Proteins; Rest; Role; Self Perception; Self-control as a personality trait; Semantics; Severities; Site; Social Behavior; Social Functioning; Staging; Symptoms; Syndrome; System; Testing; Visceral; behavioral variant frontotemporal dementia; brain behavior; brain dysfunction; clinical Diagnosis; cohort; contagion; design; diagnostic accuracy; disease phenotype; driving behavior; emotional symptom; improved; nervous system disorder; network dysfunction; neural model; neuropathology; relating to nervous system; social; social norm; theories; tool

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.

描述（由申请人提供）：额颞叶痴呆（bvFTD）的行为变异是为数不多的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感症状的评估。直到最近，还没有社会情绪行为的测量方法在神经退行性疾病患者中得到心理测量学的验证。在最初的四年里，该项目通过成功地制定这些措施直接解决了这一问题，其中的一个子集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感行为的神经系统。这一建议建立在最近发现的基础上，即每一种主要的神经退行性疾病最初都以大脑中独特的内在连接功能网络（ICN）为目标。在bvFTD的不同临床亚型中，有三个ICNs被确定为功能障碍的初始位点：腹侧显著性网络（SN）、任务控制网络（TCN）和语义-上下文网络（SCN）。然而，无论是在正常认知还是在疾病中，人们对这些ICNs驱动的特定社会情绪行为知之甚少。通过确定这些测试如何反映网络连通性，我们可以使用它们更容易地筛查早期bvFTD患者，测量症状进展，并更好地预测患者潜在的神经病理学。该项目的具体目的是阐明这三个神经网络对bvFTD的正常社会行为和社会情绪症状的贡献：目的1：阐明健康正常成年人的三个bvFTD网络如何对应社会情绪行为和认知。我们将收集40名年轻对照者（年龄20-45岁）的静息状态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者（年龄45-90岁）收集的数据。我们假设内在情绪反应的测量得分与SN连通性相关；社会自我控制与TCN连通性相关；和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社交功能障碍严重程度的关系。我们将收集50名bvFTD患者的rsMRI和社交数据，当这些数据与本项目第一阶段收集的数据相结合时，将提供足够的力量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早期出现的社会情绪和网络功能障碍。为了实现这一更具探索性的目标，我们将每年从30名症状前携带者（PC）和30名来自ftd致病基因突变家庭的非携带者（NONC）的队列中收集rsMRI和社会数据，以检查后来发展为行为表型的PC的社会情绪功能进行性变化模式，并确定PC的社会情绪变化与三个icn的连接改变相对应。