Identifying the Neural Basis and Functional Role of Emotional Empathy in Dementia

描述(由申请人提供)：这是为加州大学旧金山记忆和衰老中心(MAC)的神经心理学研究员弗吉尼亚·斯特姆博士申请K23奖项。斯特姆博士正在确立自己作为一名年轻研究员的地位，她对神经退行性疾病中的情绪进行了面向患者的临床研究。K23将为Sturm博士提供必要的支持，以实现以下目标：(1)获得神经退行性疾病、鉴别诊断和行为神经学方面的专业知识；(2)通过学习一种新方法--面部肌电图来提高她的心理生理学知识；(3)熟练掌握结构和功能神经成像分析；(4)获得真实世界行为的临床测量经验；(5)学习高级统计技术；以及(6)发展独立的研究事业。为了实现这些目标，Sturm博士组建了一个指导团队，其中包括两位主要导师：Howard Rosen博士(在神经退行性疾病、心理生理学和结构神经成像方面有专长的神经科医生)和William Seeley博士(在神经病理学、功能神经成像和“静息状态”网络连通性分析方面有专长的神经科医生)；两位共同导师：Bruce Miller博士(在行为神经学、神经变性疾病和临床研究方面有专长的神经科医生)和Robert Levenson博士(在心理生理学、情绪和共情方面有专长的心理学家)；和三位顾问：James Gross博士(在心理生理学、面部肌电和情绪方面具有专业知识的心理学家)、John Neuhaus博士(在高级多元统计分析方面具有专业知识的生物统计学家)和加里·格洛弗博士(在功能磁共振成像方法方面具有技术专业知识的核磁共振物理学家)。这项拟议的研究项目侧重于情感共鸣，这是一种通过生理和行为镜像机制发生的对他人的自动情感反应。Sturm博士将使用基于实验室的情绪测量方法来测量行为变异型额颞叶痴呆(BvFTD)患者、阿尔茨海默病(AD)患者和健康对照受试者(目标1)的两种形式的情感移情(即面部模仿和自主神经反应)。Sturm博士将把情感共鸣的实验室测量与神经成像和临床数据相结合，以确定与bvFTD中的情感共情受损和AD中的保留相关的神经系统(目标2)，并确定情感共情缺陷对现实世界行为的影响(目标3)。数据收集将在MAC和加州大学伯克利分校进行。[通过详细描述特定的、与同理心相关的、bvFTD脆弱的神经网络，这些研究将为bvFTD的疾病模型提供信息，并建议用于测量疾病进展和治疗反应的成像生物标记物。Sturm博士的K23培训将为她进行神经退行性疾病中情绪的跨学科研究做好准备，并进行未来的研究，详细说明各种临床疾病中情绪障碍的神经解剖学基础。] 公共卫生相关性：[更好地了解共情功能障碍背后的神经解剖学系统，对于改进行为变异性前额颞叶痴呆的动物模型，并通过识别最相关的大脑结构来加强人类的药物开发工作至关重要。这些信息还可能改进其他疾病的疾病模型，在这些疾病中，社会情绪缺陷是其核心特征。]

DESCRIPTION (provided by applicant): This is an application for a K23 award for Dr. Virginia Sturm, a neuropsychology fellow at the University of California, San Francisco Memory and Aging Center (MAC). Dr. Sturm is establishing herself as a young investigator who conducts patient-oriented clinical research on emotion in neurodegenerative disease. This K23 will provide Dr. Sturm with the support necessary to accomplish the following goals: (1) to gain expertise in neurodegenerative disease, differential diagnosis, and behavioral neurology; (2) to advance her knowledge of psychophysiology by learning a new method, facial electromyography; (3) to become proficient in structural and functional neuroimaging analyses; (4) to obtain experience with clinical measures of real-world behavior; (5) to learn advanced statistical techniques; and (6) to develop an independent research career. To achieve these goals, Dr. Sturm has assembled a mentoring team that includes two primary mentors: Drs. Howard Rosen (a neurologist with expertise in neurodegenerative disease, psychophysiology, and structural neuroimaging) and William Seeley (a neurologist with expertise in neuropathology, functional neuroimaging, and "resting state" network connectivity analyses); two co-mentors: Drs. Bruce Miller (a neurologist with expertise in behavioral neurology, neurodegenerative disease, and clinical research) and Robert Levenson (a psychologist with expertise in psychophysiology, emotion, and empathy); and three consultants: Drs. James Gross (a psychologist with expertise in psychophysiology, facial electromyography, and emotion), John Neuhaus (a biostatistician with expertise in advanced multivariate statistical analyses), [and Gary Glover (an MRI physicist with technical expertise in functional magnetic resonance imaging methodologies)]. The proposed research project focuses on emotional empathy, an automatic affective reaction to others that occurs via physiological and behavioral mirroring mechanisms. Dr. Sturm will use laboratory-based measures of emotion to measure two forms of emotional empathy (i.e., facial mimicry and autonomic reactivity) in patients with behavioral variant frontotemporal dementia (bvFTD), patients with Alzheimer's disease (AD), and healthy control subjects (Aim 1). Dr. Sturm will integrate laboratory measures of emotional empathy with neuroimaging and clinical data in order to identify the neural systems that are related to emotional empathy impairment in bvFTD and preservation in AD (Aim 2) and to determine the real-world behavioral impact of emotional empathy deficits (Aim 3). Data collection will take place at the MAC and at the University of California, Berkeley. [By detailing specific, empathy-relevant, bvFTD-vulnerable neural network, these studies will inform disease models of bvFTD and suggest imaging biomarkers for measuring disease progression and treatment response. Dr. Sturm's K23 training will prepare her to conduct interdisciplinary studies of emotion in neurodegenerative disease and to conduct future studies that detail the neuroanatomical bases of emotional dysfunction in various clinical disorders.] PUBLIC HEALTH RELEVANCE: [A better understanding of the neuroanatomical system that underlies empathic dysfunction will be crucial for improving animal models of behavioral variant front temporal dementia and enhancing drug development efforts in humans by identifying the most relevant brain structures. This information may also improve disease models of other disorders in which socioemotional deficits are a central feature.]