Neurophysiological Correlates of Cognition Over Multi-Day Timescales in Epilepsy - PROJECT SUMMARY/ABSTRACT Neurocognitive disorders in epilepsy are common and lead to significant morbidity and decline in quality of life. While there are many tools to reduce seizures, our tools to manage cognitive dysfunction are limited. One problem is that much of our understanding of cognitive impairment in epilepsy has been limited to short timescales of minutes, though patients often complain of fluctuating difficulties over days to weeks. Moreover, cognitive impairments over longer timescales of days to weeks have been observed in epilepsy patients, even when their standard neuropsychological testing is normal. Understanding cognition over multi-day timescales is, therefore, essential to improving the quality of life of patients. This proposal will leverage innovative, home-based digital cognitive assessments to investigate short- and long-term memory, as well as day-to-day fluctuations in cognition over weeks, in patients with temporal lobe epilepsy (TLE). In a series of prospective human studies, the candidate will test the hypothesis that impaired cognition over multi-day timescales in epilepsy is associated with fundamental alterations in sleep micro- architecture, impaired sleep functional connectivity, and fluctuations in overnight interictal epileptiform activity (IEA). To do this, neurophysiology data will be collected in parallel with cognitive tests in two unique TLE cohorts: 1) patients admitted to the Epilepsy Monitoring Unit (EMU) who are undergoing continuous EEG recordings, and 2) patients implanted with the Responsive Neurostimulator (RNS) device, allowing for long-term quantification of hippocampal IEA. The overarching goal of this proposal is to advance our understanding of the neurophysiological basis of cognitive impairment in epilepsy over a timescale that is directly relevant to the day- to-day experiences of patients. This K23 Mentored Patient-Oriented Research Career Development Award outlines a comprehensive five-year training plan for the candidate that will allow him to develop into an independent physician-scientist and an expert in the neurocognitive comorbidities of epilepsy, at the intersection of cognitive neuroscience, sleep neurophysiology, and epileptology. Key gaps in training that will be targeted for further development will include: 1) advanced biostatistics in clinical research; 2) sleep physiology; and 3) neuropsychological research methods and the use of digital home-based cognitive assessments. Rigorous coursework and conferences will supplement hands-on practical experience guided by an expert mentorship and advisory team. Capitalizing on the rich research environment at Mass General Brigham this proposal provides a framework for the candidate to develop a robust independent research program at the forefront of epilepsy and cognitive neuroscience.
