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Slow-Wave Sleep Enhancement to Treat Epilepsy

Award Number: F31NS149760
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 12/15/2026
PERIOD OF PERFORMANCE END DATE: 12/14/2027

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Slow-Wave Sleep Enhancement to Treat Epilepsy - PROJECT SUMMARY/ABSTRACT Epilepsy is a common and debilitating neurological disorder that affects over 70 million people worldwide. The ongoing development of antiseizure medications has been unsuccessful in addressing patient needs, with seizures remaining uncontrolled for a third of patients and most experiencing drug side effects. Therefore, there is a critical need for alternative approaches to treating epilepsy. Sleep and epilepsy share a complex bidirectional relationship in which sleep disturbances are likely driven by epilepsy and can worsen epilepsy. Notably, the treatment of obstructive sleep apnea in epileptic patients improves sleep quality and simultaneously improves seizure control. However, no study has investigated whether directly enhancing sleep improves epileptic outcomes in humans or animal models of epilepsy. This has been largely due to a lack of methods to selectively enhance sleep and rigorously analyze chronic sleep and epilepsy datasets. The training team has overcome these technical barriers and, for the first time to our knowledge, will determine the effects of enhancing slow- wave sleep (SWS) in two carefully selected, distinct mouse models of human epilepsy. SWS in rodents is synonymous with non-rapid eye movement (NREM) sleep and was selected for enhancement as it comprises a majority of rodent sleep, has well-established roles in physiological and cognitive functioning, and recent evidence in humans suggests that it reduces seizures compared to the lighter stages of NREM sleep. Prolonged SWS with high intensity, measured as slow-wave activity (SWA, 0.5–4 Hz) in the electroencephalogram, will be induced through chemogenetic activation of the GABAergic neurons in the parafacial zone. I hypothesize that SWS enhancement will reduce seizures and interictal epileptiform discharges in two distinct mouse models of human epilepsy. In Aim 1, I will determine the effect of SWS enhancement in a mouse model of temporal lobe epilepsy, as it is the most common form of epilepsy, highly drug-resistant, and features seizures primarily during wakefulness. In Aim 2, I will assess the effect of SWS enhancement in a mouse model of autosomal-dominant sleep-related hypermotor epilepsy, a rare genetic epilepsy in which seizures in humans occur nearly entirely during sleep. By contrasting these models, we will gain an understanding of the generality or limitations of SWS enhancement to reduce epileptogenicity. This work is critical for the large, untreated epileptic population and relevant due to the ongoing development and success of SWS enhancement techniques in humans. This project will be performed under the mentorship of Dr. Nigel Pedersen (sponsor) and Dr. Christelle Anaclet (co-sponsor), who are renowned for their contributions to the sleep-wake and epilepsy fields. I will receive rigorous training in murine surgery, chemogenetics, and electrophysiological analysis of sleep-wake states and epilepsy. The proposed research is tailored to provide me with the basis for a future career as an independent investigator conducting sleep and epilepsy research.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $43,749 )
2026	2026	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR STE 300	DAVIS	CA	95618	YOLO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	6/19/2026	NEW	$43,749
														Subtotal = $43,749

Grand Total All Awards = $43,749

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Slow-Wave Sleep Enhancement to Treat Epilepsy

Award Number: F31NS149760

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 12/15/2026

PERIOD OF PERFORMANCE END DATE: 12/14/2027

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