# Implication of the lateral hypothalamus in the comorbid sleep disorder of temporal lobe seizure

> **NIH NIH R21** · EMORY UNIVERSITY · 2022 · $500,500

## Abstract

Abstract
Epilepsy, the occurrence of spontaneous recurrent seizures, is one of the most common neurological disorders.
These recurring seizures result in a wide range of comorbidities that further reduce a patient’s quality of life and
could interfere with the diagnosis and treatment of their epilepsy. In particular, patients suffering from temporal
lobe epilepsy have frequent and severe sleep disorders such as excessive daytime sleepiness. Numerous brain
areas are involved in regulation of wakefulness and could be involved in the generation of these comorbid sleep
disorders. Among them, the orexinergic neurons of the lateral hypothalamus (LH) have been shown to control
arousal and wakefulness but have also been shown to be involved in the modulation of epileptic activity. We
hypothesize that temporal lobe seizures may disrupt the normal function of the LH leading to changes in
nocturnal sleep architecture and excessive daytime sleepiness. The interaction between sleep and epilepsy is
complex and difficult to study in patients due to confounding factors such as medication and environment. While
the environment can be controlled in rodent studies, there are distinct differences between the human and rodent
circadian cycles and sleep architectures, limiting the translational value. Alternatively, rhesus macaque
nonhuman primates have a sleep architecture like humans with four distinct sleep stages, and temporal lobe
seizures can be safely induced by injecting penicillin into the temporal lobe. Acute seizures will be induced by
local injection of penicillin into the hippocampus which will result in a succession of spontaneous seizures and
interictal activity for a period of 4-6 hours. In Aim 1, we will characterize the electrophysiological changes of the
LH during these temporal lobe seizures. We will record unit and local field activity and analyze the changes in
firing rate and pattern induced by seizures and interictal activity. We expect to find a strong involvement of LH
neurons during the seizures. In Aim 2, we will evaluate the comorbid sleep disorders associated with temporal
lobe seizures. We will test the excessive daytime sleepiness and evaluate the changes in the nocturnal sleep
architecture at different timepoints following seizure induction, and how normal sleep architecture can be
restored with administration of an orexin antagonist. Following seizure induction, we expect to find a disruption
of sleep architecture, reduction of REM duration, and an increase of daytime sleepiness, which can be
ameliorated with administration of suvorexant, an orexin antagonist. This work will provide key preliminary data
for a subsequent study to investigate more extensively the involvement of the LH neurons and orexin activity in
the control of seizures and the comorbid sleep disorders associated with temporal lobe seizures.

## Key facts

- **NIH application ID:** 10593766
- **Project number:** 1R21NS125287-01A1
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Annaelle Devergnas
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $500,500
- **Award type:** 1
- **Project period:** 2022-09-01 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10593766

## Citation

> US National Institutes of Health, RePORTER application 10593766, Implication of the lateral hypothalamus in the comorbid sleep disorder of temporal lobe seizure (1R21NS125287-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10593766. Licensed CC0.

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