Measuring Electrical Activity from the Human Brain to Predict Memory Formation and Behavior Across the Lifespan

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PROJECT SUMMARY (not changed from the original parent R00 submission) Memory is core to human cognition, undergoes protracted developmental maturation and age- related decline, and is disrupted in numerous neurological and neuropsychiatric disorders. Despite the central role of memory in health and disease, remarkably little is known about the neural mechanisms supporting memory across the human lifespan. This R00 project will combine rare intracranial recordings from neurosurgical patients and advanced electrophysiological data analysis to track memory formation and maintenance in real time, and predict behavior in children, adolescents, and adults. With these spatiotemporally precise measures of memory formation and maintenance, this research will address critical gaps in knowledge about this core neurocognitive function. Comparative analysis between intracranial recordings and scalp electroencephalography (EEG) measures will further identify noninvasive EEG metrics applicable to developmental, lifespan, and disease-related research.As a tenure- track independent investigator at Northwestern University Feinberg School of Medicine, the PI will continue and expand on the progress made during the K99 phase in two complementary, innovative directions. Aim 1 will map predictors of memory formation and maintenance from the level of single neurons to that of large-scale neural circuits using simultaneous recordings obtained from medial temporal and prefrontal regions in adults. Aim 2 will define electrophysiological predictors of memory success across the lifespan using intracranial recordings obtained from medial temporal and prefrontal regions in children, adolescents, and adults. The overarching hypothesis is that sub-second interactions in medial temporal, prefrontal, and medial temporal-prefrontal circuits will predict individual memory formation. Completion of these Aims will generate novel mechanistic explanations of human memory formation from childhood into adulthood. This research is directly relevant to Priorities #6 and #7 of the BRAIN 2025 Report. New in this R00 transition proposal is the additional collection of single-unit neuronal data from pediatric patients in preparation for the PI to submit an independent R01 application by the end of the funding period. This R00-funded work will establish one of the first single-unit pediatric research programs to exist nationally or internationally.