# Cortico-Hippocampal Circuit Dynamics in Humans

> **NIH NIH U19** · UNIVERSITY OF WASHINGTON · 2020 · $620,743

## Abstract

PROJECT SUMMARY: The ability to learning rapidly is one of the defining features of human cognition.
Despite its importance, the circuit mechanism that governs rapid learning in humans is unknown. It has been
proposed that prior-knowledge or a “mental schema” facilitates rapid learning via prefrontal-hippocampal
network interactions to improve acquisition of novel associative memory. There is, however, limited empirical
evidence supporting this model of learning. Moreover, comparisons of circuit dynamics underlying rapid
learning have not been conducted between humans and nonhuman primates. The proposal bridges systems
neuroscience across primate species and addresses three fundamental knowledge gaps: 1) Circuit dynamics
between the prefrontal cortex and hippocampus that support associative and categorical learning, 2) The
influence sleep overnight on memory retention, 3) Commonalities and differences in neural activity and circuit
dynamics between human and nonhuman primates during learning. To establish cross-species comparisons,
we will conducts a set of experiments in humans tightly linked to the nonhuman primate projects to elucidate
the circuit mechanisms of cortical-hippocampal interactions during rapid schema-based and categorical
learning. The pre-surgical evaluation of patients with epilepsy provides a unique and potent opportunity to
study these brain networks directly. Specially, we will use large-scale high-density intracranial electrodes to
record neural signals from prefrontal cortex and hippocampus while patients perform associative and
categorical learning. We will also leverage the unique ability to record single neurons in the human
hippocampus and medial prefrontal regions to directly compare neural activity across species. Our studies will
greatly advance the neurobiology of learning and memory, for which impairments form core clinical features of
diverse neurological disorders such as Alzheimer's disease, autism, major depression, and epilepsy.
Understanding the neural mechanisms of rapid learning will provide critical framework to develop circuit
specific intervention in people with disordered memory.

## Key facts

- **NIH application ID:** 9983228
- **Project number:** 5U19NS107609-03
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Robert Thomas Knight
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $620,743
- **Award type:** 5
- **Project period:** 2018-09-15 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9983228

## Citation

> US National Institutes of Health, RePORTER application 9983228, Cortico-Hippocampal Circuit Dynamics in Humans (5U19NS107609-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9983228. Licensed CC0.

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