Exploring the role of epileptiform activity in Alzheimer's Disease

项目总结/摘要 候选人是马萨诸塞州总医院的癫痫病学家和神经科学家 (MGH)和哈佛医学院，其长期职业目标是成为一个独立的- ly资助的翻译研究人员在癫痫和癫痫之间的边界的专业知识， 神经退行性疾病患有神经退行性疾病的患者的风险增加， 发展中的癫痫，并且患有癫痫的患者经常患有认知共病。的 能够将临床经验，研究工具和知识框架从 癫痫领域的神经退行性疾病，反之亦然，可能是一个强大的 研究这两个过程的方法。在拟议的培训期间，候选人将 联合收割机结合她之前在癫痫，EEG信号处理和机器学习方面的培训， 获得神经成像（功能性MRI），生物统计学和其他临床接触的技能， 神经退行性疾病患者。在悉尼·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， 作为阿尔茨海默病（AD）和神经成像方法的专家，候选人提出， 目的：1）描绘AD早期癫痫样活动的频谱，并开发计算模型， 2）建立相关的病理生理机制， AD中的癫痫样活动;以及3）确定癫痫样异常如何与 早期AD患者的认知轨迹。对24- 30年来 小时的头皮脑电图将与静息状态和基于任务的功能磁共振成像测量相结合，艾米- 从AD受试者中进行的Lloid PET成像和纵向认知测试，以开发一种复合 对AD早期癫痫样异常作用的深入了解。此外， 根据研究建议，候选人的职业发展计划需要严格的 课程和研讨会，实践动手经验，并从董事会的密切指导， 学术顾问具有不同的临床和科学专业知识。拟议的培训将使 候选人建立一个临床和研究利基之间的边界癫痫和 神经退行性疾病，并开发一个全面的工具箱， 从神经生理学、结构、连接性和焦油的角度来看人类大脑的功能 获得病理学。总的来说，这些将构成一个成功的职业生涯的基础，作为一个inde- 正在进行重要的临床和转化研究项目的研究人员， 癫痫、神经退行性疾病或两者的诊断和治疗。

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.