Dynamic neural systems underlying socioemotional function

项目摘要 这是一份来自博士后Lorenzo Pasquini博士的独立之路奖（K99/R 00）申请书。 加州大学旧金山弗朗西斯科记忆与衰老中心（MAC）临床神经影像学学者 （UCSF）。Pasquini博士是一位早期职业神经科学家，他研究的是 神经退行性疾病的社会情绪症状。帕斯奎尼博士有很强的背景， 神经科学，临床神经成像和机器学习技术，但他需要指导研究， 在四个不同领域接受高级别培训，成为一名独立调查员。培训和 本提案中概述的研究计划将为Pasquini博士提供必要的支持， 以下目标：1）在社会情绪症状的临床表现中获得广泛的专业知识， 老年人群体; 2）通过应用多模态动态系统的分析， 尖端的机器学习算法; 3）熟练掌握自主生理分析 记录;以及4）根据科学生产力和赠款开发独立的研究职业利基 应用.为了实现这些目标，Pasquini博士组建了一个导师团队，其中包括一名主要导师， 博士威廉塞利，行为神经学家，在神经解剖学和神经影像学方面有很深的专业知识， 神经退行性疾病;一位共同导师，弗吉尼亚·斯特姆博士，一位研究自主神经的临床心理学家 和社会情绪缺陷在不同的痴呆综合征;第二个共同导师，博士Manish Saggar，一个 计算神经科学家开发计算方法，以绘制健康和 精神病人群;以及一个重要的贡献者，伊莎贝尔艾伦博士，一位机器学习方面的统计学家专家。 该提案描述了创新技术的应用，旨在阐明自主系统如何 和大脑动态地相互作用，以塑造健康对照组和患有 神经退行性综合征通过利用行为神经系统中的神经解剖学和自主神经缺陷， 变异性额颞叶痴呆症（bvFTD），Pasquini博士试图确定神经系统的基本特性， 社会情感幸福的基础系统，对精神病学具有重要意义，其中神经生物学 潜在的情感障碍还不太清楚。帕斯奎尼博士将首先描述动态大脑的缺陷 bvFTD患者的网络组织，并探索与社会情绪症状的关系（目的1）。 博士Pasquini将通过确定bvFTD患者的动态自主神经流出功能缺陷来进行研究，并评估 通过单独获得的神经成像（Aim 2）进行神经相关性分析。最后，帕斯奎尼博士将利用 健康老年人自主神经流出和脑网络成像的多模式同时采集 控制，以探索这两个系统如何动态地相互作用，以维持人类的情感和社会行为 （探索目标3）。拟议的培训将使帕斯基尼博士能够发展一个科学利基，并进行他的 在世界一流的指导下进行研究，为他作为独立研究人员的职业生涯铺平了道路。

PROJECT SUMMARY This is an application for a Pathway to Independence Award (K99/R00) from Dr. Lorenzo Pasquini, a postdoctoral scholar in clinical neuroimaging at the Memory and Aging Center (MAC), University of California, San Francisco (UCSF). Dr. Pasquini is an early-career neuroscientist investigating the neural systems underlying socioemotional symptoms in neurodegenerative diseases. Dr. Pasquini has a strong background in neuroscience, clinical neuroimaging, and machine-learning techniques, but he requires mentored research and high-level training in four different areas to become established as an independent investigator. The training and research program outlined in this proposal will provide Dr. Pasquini with the support necessary to accomplish the following goals: 1) gain extended expertize in the clinical manifestation of socioemotional symptoms among elderly populations; 2) achieve proficiency in analysis of multimodal dynamic systems through the application of cutting-edge machine-learning algorithms; 3) get proficiency in the analysis of autonomic physiological recordings; and 4) develop an independent research career niche based on scientific productivity and grant applications. To achieve these goals, Dr. Pasquini has assembled a mentorship team including a primary mentor, Dr. William Seeley, a behavioral neurologist with deep expertize in neuroanatomy and neuroimaging of neurodegenerative diseases; a co-mentor, Dr. Virginia Sturm, a clinical psychologist who investigates autonomic and socioemotional deficits across distinct dementia syndromes; a second co-mentor, Dr. Manish Saggar, a computational neuroscientist developing computational methods to map dynamic brain activity in healthy and psychiatric populations; and a significant contributor, Dr. Isabel Allen, a statistician expert in machine-learning. This proposal describes the application of innovative techniques that aim to elucidate how the autonomic system and the brain dynamically interact to shape emotions and social behavior in healthy controls and patients with neurodegenerative syndromes. By leveraging the neuroanatomical and autonomic deficits found in behavioral variant frontotemporal dementia (bvFTD), Dr. Pasquini seeks to identify the fundamental properties of neural systems underlying socioemotional well-being, with important implications for psychiatry where the neurobiology underlying affective disorders is not well understood. Dr. Pasquini will first delineate deficits in dynamic brain network organization in patients with bvFTD and explore the relationship to socioemotional symptoms (Aim 1). Dr. Pasquini will proceed by identifying deficits in dynamic autonomic outflow in patients with bvFTD and assess the neural correlates through separately acquired neuroimaging (Aim 2). Finally, Dr. Pasquini will capitalize on multimodal simultaneous acquisitions of autonomic outflow and brain network imaging acquired in healthy older controls to explore how both systems dynamically interact to sustain human emotions and social behavior (Exploratory Aim 3). The proposed training will allow Dr. Pasquini to develop a scientific niche and conduct his research with world-class mentorship, paving the way for his career as an independent researcher.