Reward processing in frontotemporal dementia

描述（由申请人提供）：这是加州大学旧金山记忆与衰老中心（MAC）行为神经学研究员David Perry博士的K23奖申请。佩里博士在神经退行性疾病中奖赏处理的以患者为导向的临床研究方面正在成为一名年轻的研究者。K23奖将为Perry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和神经精神症状管理方面的专业知识；2)熟练使用和分析结构和功能神经成像；3)积累使用心理生理指标的经验；4)提高他对生物统计学[和临床试验]的认识；5)发展独立的临床研究事业。为了实现这些目标，佩里博士组建了一个由两位主要导师组成的指导团队：霍华德·罗森（Howard Rosen）博士（神经退行性疾病、心理生理学和神经成像分析方面的专家）和乔尔·克莱默（Joel Kramer）博士（认知和行为系统方面的专家）；一位共同导师Bruce Miller博士（在行为神经学、神经退行性疾病和临床研究方面具有专长的神经学家）；以及五位顾问：Craig Nelson博士（老年精神病学家）、Chiadi Onyike博士（老年精神病学家和行为变异额颞叶痴呆（bvFTD）专家）、Adam Boxer博士（具有bvFTD临床试验专业知识的神经学家）、John Neuhaus博士（生物统计学家）和Mark D'Esposito博士（具有功能性神经成像和奖励处理专业知识的神经科学教授）。拟议的研究将检查bvFTD的奖励处理。奖励处理包括决定一个人会追求什么或为什么而工作，比如食物、金钱或社会认可。Perry博士将对bvFTD患者、阿尔茨海默病患者和健康对照者进行奖励处理的实验室任务，以确定bvFTD患者对奖励的评估方面的改变（目的1）。Perry博士将把这些实验室任务的发现与结构和功能成像联系起来，以确定这些行为的解剖学相关性（目标2），并与现实生活中的功能测量联系起来，以确定奖励处理变化对患者生活的影响（目标3）。数据收集将在MAC进行。本研究的结果将提高对bvFTD行为症状的理解，将指导该疾病的对症治疗的未来研究，将提供客观的测试来区分神经退行性疾病，并将提供基于奖励的措施作为bvFTD动物模型中使用的额外工具。这种K23训练将使佩里博士能够将奖励处理的概念应用于对其他神经退行性疾病的理解。

DESCRIPTION (provided by applicant): This is an application for a K23 award for Dr. David Perry, a behavioral neurology fellow at the University of California, San Francisco Memory and Aging Center (MAC). Dr. Perry is establishing himself as a young investigator in patient-oriented clinical research of reward processing in neurodegenerative disease. This K23 award will provide Dr. Perry with the support necessary to accomplish the following goals: 1) to gain expertise in neurodegenerative disease and neuropsychiatric symptom management; 2) to develop proficiency in the use and analysis of structural and functional neuroimaging; 3) to gain experience in the use of psychophysiological measures; 4) to advance his knowledge of biostatistics [and clinical trials]; and 5) to develop an independent clinical research career. To achieve these goals, Dr. Perry has assembled a mentoring team comprised of two primary mentors: Dr. Howard Rosen (a neurologist with expertise in neurodegenerative disease, psychophysiology, and neuroimaging analysis) and Dr. Joel Kramer (a neuropsychologist with expertise in cognitive and behavioral systems); one co-mentor, Dr. Bruce Miller (neurologist with expertise in behavioral neurology, neurodegenerative disease, and clinical research); and five consultants: [Dr. Craig Nelson (a geriatric psychiatrist), Dr. Chiadi Onyike (a geriatric psychiatrist and specialist in behavioral variant frontotemporal dementia (bvFTD)), Dr. Adam Boxer (a neurologist with expertise in clinical trials in bvFTD),] Dr. John Neuhaus (a biostatistician) and Dr. Mark D'Esposito (a professor of neuroscience with expertise in functional neuroimaging and reward processing). The proposed research will examine reward processing in bvFTD. Reward processing involves a determination of what an individual will pursue or work for, such as food, money, or social approval. Dr. Perry will administer laboratory tasks of reward processing to patients with bvFTD, Alzheimer's disease, and healthy control subjects to determine the aspect of valuation of reward that is altered in bvFTD (Aim 1). Dr. Perry will correlate the findings from these laboratory tasks with structural and functional imaging to determine the anatomic correlates of these behaviors (Aim 2) and with real-life functional measures to determine the effect reward processing changes have in patients' lives (Aim 3). Data collection will take place at the MAC. The results of this research will improve understanding of the behavioral symptoms in bvFTD, will direct future studies into symptomatic treatment in the illness, will provide objective tests to distinguish neurodegenerative diseases, and will offer reward-based measures as an additional tool for use in animal models of bvFTD. This K23 training will enable Dr. Perry to apply concepts of reward processing to the understanding of other neurodegenerative diseases.