# In Vivo Studies of the Epileptic Hippocampus

> **NIH NIH RF1** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2023 · $3,630,462

## Abstract

PROJECT SUMMARY (ABSTRACT)
The World Health Organization includes dementia and epilepsy among the top four primary diseases of the brain. Our
research proposal concerns the fact that patients with mesial temporal lobe epilepsy (MTLE) and hippocampal sclerosis
(HS), the most common drug resistant form of epilepsy, have an increased risk of developing dementia, and that more
patients with Alzheimer Disease (AD) have epileptogenic abnormalities than previously suspected. Whereas classical
MTLE begins in childhood and is characterized by unilateral HS with CA2 sparing, we are seeing an increasing number of
patients with adult onset MTLE, more diffuse HS, and contralateral involvement. Furthermore, hippocampal specimens
resected to treat drug resistant MTLE are more likely to contain plaques and tau than age matched controls. On the other
hand, not only are 10-22% of patients with AD known to have overt epilepsy, but also there is increasing evidence that a
much greater percentage have subclinical seizures, or epileptiform EEG abnormalities. In order to investigate the
relationship between seizures and cognitive decline in MTLE and AD, we are proposing to carry out reiterative translational
retro- and prospective studies in patients with adult onset MTLE, and prospective studies on patients with AD and mild
cognitive impairment (MCI), as well as a rat model of AD with epileptic seizures. Our Specific Aims are: 1a: In patients
with AD and MCI who exhibit epileptic activity and HFOs on overnight scalp EEG, perform hippocampal depth electrode
recordings over 5 days to further characterize EEG and HFOs and perform hippocampal and neocortical SPM of MRI, for
comparison with MTLE and rat data. (in the near future we will also be able to use MEG). 1b: Carry out pathological
analysis of hippocampal specimens for tau and plaques from subjects with MTLE who undergo surgical resection in Aim
1a for correlation with electrophysiology, imaging, age of onset, and cognitive testing. 2a:In a rat model of AD with
epilepsy, monitor EEG, HFOs, LFPs, and MUA, and perform hippocampal and neocortical SPM of MRI, for comparison
with data already obtained from intrahippocampal kainate (IHKA) rats. Correlate disturbances in hippocampal-prefrontal
cortex connectivity with development of cognitive disfunction. 2b: In the same rat model, perform electrophysiological and
behavioral testing before and after treatment with brivaracetam and compare effects with animals in Aim 2a.
electrophysiological activity will identify patients with MCI and AD who will benefit from antiseizure therapy. 3a: In the
same patients with AD and MCI as Aim 1a, perform hippocampal depth recordings of epileptic activity and HFOs before
and after low-dose brivaracetam. 3b: In patients with AD and MCI from Aim 1a, who show epileptogenic
electrophysiological features, perform cognitive testing before and after one month of treatment with brivaracetam.
Long-term goals: Based on the results of these studies, ...

## Key facts

- **NIH application ID:** 10596945
- **Project number:** 2RF1NS033310-27
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** JEROME NONE ENGEL
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $3,630,462
- **Award type:** 2
- **Project period:** 1994-08-01 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10596945

## Citation

> US National Institutes of Health, RePORTER application 10596945, In Vivo Studies of the Epileptic Hippocampus (2RF1NS033310-27). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10596945. Licensed CC0.

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