# Peri-ictal respiratory and arousal disturbances in focal epilepsy: Role of the brainstem

> **NIH NIH R56** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2023 · $433,085

## Abstract

Project Summary/Abstract
Epilepsy is the fourth most common neurological disease in the US. 20-30% of the patients with epilepsy (PWE)
continue to experience seizures despite adequate drug treatment which puts them at risk for sudden unexpected
death in epilepsy (SUDEP). SUDEP typically occurs in the postictal recovery phase and is characterized by
impaired arousal followed by cardiorespiratory breakdown suggesting a shutdown of critical brainstem functions.
However, respiratory disturbances severe enough to cause peri-ictal hypoxemia (PIH) and signs of impaired
arousal such as widespread post-ictal EEG slowing (PIES), or postictal generalized EEG suppression (PGES)
occur also during non-fatal seizures. The mechanisms of PIH, PIES and PGES and how they relate to SUDEP
are not well understood. The overall goal of this project is therefore to use MRI to characterize structural and
functional alterations of the brainstem systems controlling respiration and arousal in drug-resistant epilepsy and
to investigate how they influence the occurrence of these non-fatal disturbances. This will not only allow for a
better understanding of the mechanism underlying these common peri-ictal disturbances but also provide
insights how they relate to SUDEP. Specifically, it is hypothesized that PIH is a consequence of structural and
functional disturbances of the midbrain respiratory modulator complex but spares the respiratory pattern
generator in the lower medulla. PIES are associated with abnormalities in the brainstem arousal network and
PGES is hypothesized to be associated with severe abnormalities in the arousal as well as respiratory modulator
network. Structural imaging and task-free fMRI will be acquired in 200 patients with drug-refractory, non-lesional
epilepsy (PWE) undergoing long-term video-EEG telemetry and SpO2 monitoring in 3 epilepsy centers. The
primary measure of interest is the occurrence (yes/no) of PIH and PIES/PGES. A new brainstem segmentation
approach will be used to identify brainstem structures of interest. Dynamic functional connectivity analysis
combining cluster analysis and graph theory will be used to identify different brain states in task free fMRI. 40
age and gender matched healthy controls (CON) will undergo the same imaging as PWE.

## Key facts

- **NIH application ID:** 10799997
- **Project number:** 1R56NS127891-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Susanne G. Mueller
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $433,085
- **Award type:** 1
- **Project period:** 2023-06-15 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10799997

## Citation

> US National Institutes of Health, RePORTER application 10799997, Peri-ictal respiratory and arousal disturbances in focal epilepsy: Role of the brainstem (1R56NS127891-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10799997. Licensed CC0.

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