Exploring the role of epileptiform activity in Alzheimer's Disease

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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.