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

基本信息

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
项目类别：
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

项目摘要

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.

抽象的额颞叶痴呆 (FTD) 是一类神经退行性综合征，其特征是进行性进展情绪、社会行为和语言下降。 FTD 的行为变异是临床上最常见的亚型，其特征是情感、同理心和社会行为方面的缺陷。 FTD 通常是零星的，但可由 C9orf72、GRN 和 MAPT 基因突变引起。 FTD 的遗传形式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、研究和当他们无症状时和进入疾病的症状阶段时进行跟踪。我们之前的基于实验室的研究发现自主神经系统活动、面部表情和体验发生在 FTD 早期，反映了特定大脑网络的功能障碍。解剖学上特定的情绪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症状轻微的个体，但需要更可扩展的方法。拟议的该项目将建立在我们之前对无症状和有症状个体的情绪进行的实验室研究的基础上与 FTD 一起，将包括对现实世界中的情绪和行为进行纵向、多天的评估。这些数据将使我们能够测试我们在实验室发现的新型情绪生物标志物是否可以用于使用远程工具进行跟踪，并使我们能够确定早期是否存在其他变化领域以前未被发现的 FTD。该提案的中心假设是情绪是直接的脆弱大脑系统的读数可用于监测无症状和早期的进展 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范围内，50 名突变非携带者家庭成员对照，50 名散发性突变患者行为变异 FTD 和 50 名老年健康对照者进行了三次年度研究访问，其中包括临床研究工作和神经影像学。我们还将进行五次每半年一次的远程情绪评估，在此期间我们将测量现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（使用经验抽样方法）。我们将解决三个关键目标。在目标 1 中，我们将绘制无症状突变中情感的现实世界图景携带者和早期 FTD 及其与情绪和情感症状实验室测量的关联。在目标 2，我们将隔离 FTD 相关情绪失常背后的神经系统，如在现实世界和实验室。在目标 3 中，我们将量化早期 FTD 中纵向情绪系统的衰退。经过将神经影像技术与实验室和现实世界的情绪测量相结合，这该项目有潜力推进当前情绪功能障碍和衰退的生物学基础模型在早期的 FTD 中。