Exploring the role of epileptiform activity in Alzheimer's Disease

项目摘要/摘要 这位候选人是麻省总医院的癫痫专家和神经学家 (MGH)和哈佛医学院，他们的长期职业目标是成为一名独立的- LY资助的翻译调查员，在癫痫和 神经退行性疾病。患有神经退行性疾病的患者患上 发展为癫痫，癫痫患者往往患有认知共病。这个 能够将临床经验、研究工具和智力框架 癫痫领域的神经退行性疾病，反之亦然，可能是一种强大的 研究这两个过程的方法。在拟议的培训期间，应聘者将 将她之前在癫痫、脑电信号处理和机器学习方面的培训与新的 掌握神经成像(功能核磁共振)、生物统计学和其他临床经验 患有神经退行性疾病的患者。在专家西德尼·卡什博士的指导下 在癫痫和神经生理信号处理方面，以及Reisa Sperling博士的共同指导下， 作为阿尔茨海默病(AD)和神经成像方法方面的专家，这位候选人建议 目的：1)描绘阿尔茨海默病(AD)早期癫痫样活动的频谱，并开发计算方法。 确定这一活动的常规工具；2)建立作为基础的病理生理机制 AD中的癫痫样活动；以及3)确定癫痫样异常如何与 早期阿尔茨海默病患者的认知轨迹。24-年的可视化和计算分析 小时头皮脑电将与静息状态和基于任务的功能磁共振测量相结合，AMY- Loid PET成像和AD受试者的纵向认知测试，以开发一个组件- 全面认识癫痫样异常在AD早期的作用。另外-- 根据所提出的研究，候选人的职业发展计划需要严格 课程和研讨会，实践实践经验，以及来自 具有不同临床和科学专业知识的学术顾问。拟议的培训将使 在癫痫和癫痫之间建立临床和研究利基的候选人 神经退行性疾病，并开发一个全面的工具箱来探索 从神经生理、结构、连通性和焦油的角度来看，人类的大脑功能-- 做了病理学检查。总而言之，这些将构成作为一名印度人成功职业生涯的基础- 悬而未决的研究人员致力于重要的临床和转译研究项目以改进 癫痫、神经退行性疾病或两者兼有的患者的诊断和治疗。

PROJECT SUMMARY / ABSTRACT The candidate is an epileptologist and neuroscientist at the Massachusetts General Hospital (MGH) and Harvard Medical School, whose long-term career goal is to become an independent- ly funded translational investigator with expertise at the boundary between epilepsy and the neurodegenerative diseases. Patients with neurodegenerative diseases are at increased risk of developing epilepsy, and patients with epilepsy often suffer from cognitive co-morbidities. The ability to translate the clinical experience, research tools, and intellectual framework from the field of epilepsy to that of the neurodegenerative diseases, and vice versa, could be a powerful approach to studying both processes. During the proposed training period, the candidate will combine her prior training in epilepsy, EEG signal processing, and machine learning, with newly acquired skills in neuroimaging (functional MRI), biostatistics, and additional clinical exposure to patients with neurodegenerative diseases. Under the mentorship of Dr. Sydney Cash, an expert in epilepsy and neurophysiologic signal processing, and the co-mentorship of Dr. Reisa Sperling, an expert in Alzheimer’s disease (AD) and neuroimaging approaches, the candidate proposes to: 1) Delineate the spectrum of epileptiform activity in early stages of AD and develop computa- tional tools to identify this activity; 2) Establish the pathophysiologic mechanisms that underlie epileptiform activity in AD; and 3) Determine how epileptiform abnormalities are associated with cognitive trajectories in patients with early stage AD. Visual and computational analysis of 24- hour scalp EEGs will be integrated with resting-state and task-based fMRI measurements, amy- loid PET imaging, and longitudinal cognitive testing from subjects with AD, to develop a com- prehensive understanding of the role of epileptiform abnormalities in early stages of AD. In addi- tion to the research proposed, the candidate’s career development plan entails rigorous coursework and seminars, practical hands-on experience, and close guidance from a board of academic advisors with diverse clinical and scientific expertise. The proposed training will allow the candidate to establish a clinical and research niche at the boundary between epilepsy and the neurodegenerative diseases, and to develop a comprehensive toolbox with which to probe human brain function from the standpoint of neurophysiology, structure, connectivity, and tar- geted pathology. Collectively, these will form the foundation for a successful career as an inde- pendent investigator pursuing important clinical and translational research projects to improve the diagnosis and treatment of patients with epilepsy, neurodegenerative diseases, or both.