# Closed-Loop Modulation of Hippocampal-Cortical Communication in Temporal Lobe Epilepsy

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA-IRVINE · 2024 · $339,120

## Abstract

PROJECT SUMMARY/ABSTRACT
Long-term memory impairment significantly impacts patients with temporal lobe epilepsy (TLE), but no targeted
treatment exists. There is a critical need to understand the mechanisms that disrupt long-term information stor-
age in the epileptic brain. The long-term goal is to develop strategies to ameliorate and prevent cognitive impair-
ment in patients with epilepsy. The overall objectives are to i) elucidate how interictal epileptic discharges (IEDs)
affect hippocampal-cortical communication during memory consolidation, and ii) determine how closed-loop
modulation of this communication alters long-term memory in an animal model of TLE. The central hypothesis
is that IEDs disrupt the interaction of hippocampal ripples and cortical sleep spindles, altering neural activity
patterns and plasticity. Further, restoration of physiologic hippocampal-cortical coupling can normalize the long-
term memory deficits observed in TLE. The rationale for this project is that elucidating the spatiotemporally spe-
cific network mechanisms that underlie long-term memory disruption will enable prevention of pathologic com-
munication without impairment of physiologic communication, thereby facilitating memory consolidation. The
central hypothesis will be tested by pursuing three specific aims in a TLE animal model: i) evaluate the effect of
modulating hippocampal-cortical oscillatory coupling on neural spiking patterns; ii) determine the effect of mod-
ulating hippocampal-cortical coupling on long-term memory, iii) establish links between large-scale molecular
markers of synaptic plasticity and hippocampal-cortical oscillatory coupling during impaired memory consolida-
tion. To accomplish these aims, in vivo electrophysiology and assays of immediate early gene expression will
be paired with closed-loop electrical stimulation in freely behaving rats performing long-term memory tasks. The
research proposed is innovative, in the applicant’s opinion, because it focuses on modulating neuronal commu-
nication between brain regions during the interictal period to enhance memory consolidation. These contributions
will be significant because they are expected to provide the mechanistic groundwork for development of novel
approaches to treat, and potentially prevent, memory impairment in patients with epilepsy.

## Key facts

- **NIH application ID:** 11115484
- **Project number:** 7R01NS118091-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Jennifer Gelinas
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $339,120
- **Award type:** 7
- **Project period:** 2021-03-15 → 2026-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11115484

## Citation

> US National Institutes of Health, RePORTER application 11115484, Closed-Loop Modulation of Hippocampal-Cortical Communication in Temporal Lobe Epilepsy (7R01NS118091-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11115484. Licensed CC0.

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