Emotion network dysfunction and decline in early frontotemporal dementia

早期额颞叶痴呆的情绪网络功能障碍和衰退

• 批准号: 10574476
• 负责人: Virginia Emily Sturm
• 金额: $ 79.65万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-12-15 至 2027-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10574476
• 关键词: Affective; Affective Symptoms; Age; Anatomy; Area; Atrophic; Autonomic nervous system; Behavior; Biological Markers; Biological Models; Brain; C9ORF72; Clinical; Clinical Trials; DNA Sequence Alteration; Data; Deterioration; Disease; Disease Progression; Emotional; Emotions; Empathy; Environment; Facial Expression; Family; Family member; Feeling; Frontotemporal Dementia; Functional disorder; GRN gene; Genes; Genetic; Goals; Impairment; Individual; Intervention; Laboratories; Language; MAPT gene; Maps; Measures; Mental disorders; Methods; Modeling; Monitor; Mutation; Nerve Degeneration; Neuroanatomy; Neurological Models; Parasympathetic Nervous System; Participant; Pathology; Patient Self-Report; Pattern; Persons; Phase; Physiology; Populations at Risk; Research; Rest; Sampling; Science; Social Behavior; Structure; Support System; Surveys; Symptoms; Syndrome; System; Techniques; Testing; Time; Visit; behavioral variant frontotemporal dementia; clinical subtypes; cohort; experience; follow up assessment; improved; innovation; longitudinal analysis; mutation carrier; nervous system disorder; network dysfunction; neural; neuroimaging; novel; novel marker; remote assessment; tool; treatment response; wearable device

ABSTRACT Frontotemporal dementia (FTD) is a family of neurodegenerative syndromes characterized by progressive decline in emotion, social behavior, and language. The behavioral variant of FTD is the most common clinical subtype and is characterized by deficits in emotion, empathy, and social behavior. FTD is often sporadic but can be caused by genetic mutations in C9orf72, GRN, and MAPT. Genetic forms of FTD offer a critical window into the disease's early stages because individuals with genetic mutations can be identified, studied, and followed when they are asymptomatic and as they enter the symptomatic stage of the disease. Our previous laboratory-based studies have found alterations in autonomic nervous system activity, facial expression, and experience occur early in FTD and reflect dysfunction in specific brain networks. Anatomically specific emotion biomarkers could be used to monitor symptom progression or treatment response in clinical trials of asymptomatic or mildly symptomatic individuals, but more scalable approaches are needed. The proposed project will build on our prior laboratory-based studies of emotion in asymptomatic and symptomatic individuals with FTD and will include longitudinal, multi-day assessments of emotion and behavior in the real world. These data will allow us to test whether novel emotion biomarkers we have discovered in the laboratory can be tracked with remote tools and will enable us to determine whether there are additional areas of change in early FTD that have previously gone undetected. The central hypothesis of this proposal is that emotions are direct readouts of vulnerable brain systems that can be used to monitor progression in the asymptomatic and early symptomatic phase of FTD. We will conduct laboratory-based assessments of emotion in 100 mutation carriers across the clinical spectrum, 50 mutation non-carrier family member controls, 50 people with sporadic behavioral variant FTD, and 50 older healthy controls at three annual research visits that include a clinical work-up and neuroimaging. We will also conduct five biannual remote assessments of emotion during which we will measure real-world autonomic physiology (with wearable devices), behavior (with participants' photographs and self-reported activities), and subjective feelings (with experience sampling methods). We will address three key aims. In Aim 1, we will map the real-world landscape of emotion in asymptomatic mutation carriers and early FTD and its associations with laboratory measures of emotion and affective symptoms. In Aim 2, we will isolate the neural systems underlying FTD-relevant aberrations in emotion as measured in the real world and laboratory. In Aim 3, we will quantify longitudinal emotion system decline in early FTD. By integrating neuroimaging techniques with measures of emotion from the laboratory and the real world, this project has the potential to advance current models of the biological basis of emotion dysfunction and decline in early FTD.

摘要 额颞叶痴呆（FTD）是一个神经退行性综合征家族，其特征是进行性痴呆， 情绪、社交行为和语言能力下降。FTD的行为变体是最常见的临床 亚型，其特征是情感、同理心和社会行为方面的缺陷。FTD通常是散发性的， 可能由C9orf72、GRN和MAPT的基因突变引起。遗传形式的FTD提供了一个关键窗口 进入疾病的早期阶段，因为具有基因突变的个体可以被识别，研究， 当他们无症状和进入疾病的症状阶段时进行随访。我们以前的 基于实验室的研究发现，自主神经系统活动、面部表情和 经验发生在FTD的早期，反映了特定脑网络的功能障碍。解剖学上的特殊情感 生物标志物可用于监测临床试验中的症状进展或治疗反应， 无症状或轻度症状的个体，但需要更可扩展的方法。拟议 该项目将建立在我们先前对无症状和有症状个体情绪的实验室研究基础上 与FTD，并将包括纵向，多日的情绪和行为的评估，在真实的世界。这些 这些数据将使我们能够测试我们在实验室中发现的新的情绪生物标志物是否可以 使用远程工具进行跟踪，并将使我们能够确定是否有其他领域的变化， 以前未检测到的FTD。这个提议的中心假设是情绪是直接的 脆弱的大脑系统的读数，可用于监测无症状和早期 FTD的症状期。我们将对100名突变携带者进行基于实验室的情绪评估 在整个临床谱中，50名突变非携带者家庭成员对照，50名散发性 行为变异FTD和50名老年健康对照者进行了三次年度研究访问， 检查和神经成像我们还将进行五次一年两次的情绪远程评估， 我们将测量真实世界的自主生理学（使用可穿戴设备），行为（使用参与者的 照片和自我报告的活动），和主观感受（与经验抽样方法）。我们将 实现三个关键目标。在目标1中，我们将绘制无症状突变中的现实世界情绪景观 携带者和早期FTD及其与情绪和情感症状实验室测量的相关性。在 目的2，我们将分离神经系统的基础FTD相关的情绪畸变，如测量中所述。 真实的世界和实验室。在目标3中，我们将量化FTD早期的纵向情绪系统下降。通过 将神经成像技术与实验室和真实的世界的情感测量相结合， 该项目有可能推进当前情绪功能障碍和衰退的生物学基础模型 早期的FTD。