# Defining the Epileptogenic Network and Identifying which Components Generate Seizures

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2021 · $545,837

## Abstract

Project Summary
 Epilepsy is a serious neurological disorder characterized by spontaneous seizures and increased risk of
mortality, especially for one-third of the individuals with chronic seizures that cannot be controlled in spite of
optimal drug therapy. Currently, the most effective treatment for drug-resistant seizures is resective surgery
and in cases such as temporal lobe epilepsy (TLE) with hippocampal sclerosis, the most common form of drug-
resistant epilepsy, surgery can reduce or eliminate seizures in most patients. However, it does not help all
patients, particularly those with seizures suspected to begin in the temporal lobe but without a MRI lesion or
MRI contains a lesion in hippocampus and neocortex or scalp EEG indicates bilaterally. In situations like these
the extent of the epileptogenic zone (EZ), which is the brain area that is necessary and sufficient for generating
seizures and minimum resection necessary for seizure relief, is uncertain. There is tremendous interest in
studies of the epileptogenic network (EN), i.e. the larger brain region that supports the generation and spread
of seizures and manifestation of epilepsy, and we hypothesize in difficult cases of TLE, knowledge of the EN
could help us to localize the EZ. Even with recent progress from studies of the EN, we still do not know the full
extent of brain abnormalities that define the EN, what part is necessary for generating seizures, or how much of
the EN needs to be removed to eliminate seizures. This project addresses these issues and we have developed a
comprehensive approach to study them, including novel structural and diffusion MRI and EEG functional
connectivity tests, as well as studies of high frequency oscillations (HFOs), which are a potential biomarker of
the EZ. We will apply this approach to presurgical patients with suspected TLE who require invasive EEG tests
as part of their standard diagnostic care. To help us define the EN in Aim 1, we will evaluate structural MRI for
gray matter abnormalities and morphological covariance between brain areas; in Aim 2, we will assess
diffusion MRI for white matter microstructural and fiber tract anomalies; in Aim 3, we will use a new approach
called gamma event coupling in combination with unit and HFO recordings to investigate the functional
connectivity encompassing the EN and identify which parts of it are generating seizures and spread; and lastly
in Aim 4, we will determine which components of the EN and how much of it needs to be removed to eliminate
seizures. In this project, defining the EN should provide important information on the structural and
functional mechanisms generating seizures, and ultimately this will help us to localize the EZ, improve
diagnosis, advance surgical and non-surgical therapies, develop new therapies, and increase the likelihood for
seizure freedom.

## Key facts

- **NIH application ID:** 10201767
- **Project number:** 5R01NS106957-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Richard Staba
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $545,837
- **Award type:** 5
- **Project period:** 2018-09-30 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10201767

## Citation

> US National Institutes of Health, RePORTER application 10201767, Defining the Epileptogenic Network and Identifying which Components Generate Seizures (5R01NS106957-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10201767. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*