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 in humans. In
this K99/R00 project, I propose to 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 non-invasive EEG metrics applicable to developmental, lifespan, and disease-related research.
Causal links between the medial temporal lobe, prefrontal cortex, and memory are well-established. However,
there is a paucity of data on the mechanisms by which medial temporal and prefrontal regions interact to support
memory in humans. The proposed research will determine the dynamic, multi-level neural circuit mechanisms
that predict memory formation in humans across the lifespan. This research program will follow two
complementary, largely unexplored directions. Aim 1 (K99 phase) 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 (R00 phase) 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 and will prepare the Principal Investigator for a successful independent research career.
To achieve these Aims, the proposed career development plan will build upon the Principal Investigator’s
previous training with four goals to enhance her trajectory toward becoming an independent investigator: (1)
analysis of single-unit neuronal data; (2) application of multivariate statistics to time-series data; (2) ethical
aspects of conducting scientific research in clinical patients; and (4) research, mentoring, and administrative
skills requisite to run a successful laboratory. Training will be accomplished through a balance of direct
mentorship from animal and human neurophysiologists and coursework in neurophysiology, statistics,
responsible conduct of research, and preparing for a future faculty position.