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Sleep-Driven Adaptive Neuromodulation in Lennox-Gastaut Syndrome

Award Number: UH3NS145998
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/15/2026
PERIOD OF PERFORMANCE END DATE: 05/31/2028

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Sleep-Driven Adaptive Neuromodulation in Lennox-Gastaut Syndrome - Project Summary Lennox-Gastaut Syndrome (LGS) is a catastrophic childhood-onset epilepsy characterized by drug-resistant seizures, severe cognitive impairments, and profound behavioral challenges. A hallmark of LGS is the heightened seizure burden during non-REM (NREM) sleep, where epileptiform discharges amplify, disrupting sleep architecture, blocking REM transitions, and worsening neurodevelopmental decline. These disruptions perpetuate seizure activity, cognitive deficits, and behavioral challenges, highlighting the urgent need for therapies targeting state-dependent epileptiform activity. During NREM sleep, synchronized thalamocortical firing pattern amplifies epileptiform discharges, while asynchronous REM activity naturally limits their propagation. The pedunculopontine tegmental region (PPT), a regulator of NREM-to-REM transitions, plays a key role in thalamocortical desynchronization and offers a promising target for modulating the synchronous state that facilitates the epileptiform activity. Building on this mechanism, ADAPT-LGS (Adaptive Deep Brain Stimulation for Advanced Precision Therapy in Lennox-Gastaut Syndrome) introduces a novel sleep-adaptive DBS strategy leveraging REM sleep’s intrinsic antiepileptogenic desynchronization effects via the Percept DBS system. Using local field potential (LFP) biosignals from the Centromedian-Parafascicular (CM-Pf) thalamus, the system detects epileptiform-rich NREM as a control signal and dynamically adjusts stimulation amplitudes to desynchronize pathological thalamocortical activity directly or indirectly via CM-Pf–PPT pathways. Specific aims include 1) identifying optimal CM-Pf stimulation sites that activate PPT and desynchronize the thalamocortical network during NREM sleep, 2) validating spectral biomarkers for epileptiform-rich NREM and motor seizures using ambulatory wearable sensors, and 3) assessing adaptive DBS’s impact on seizure burden, sleep, and patient-centric outcomes in a double-blind crossover trial comparing adaptive DBS with continuous cycling DBS. Primary and secondary outcomes will be objectively measured with seizure-detection wristwatches and wearable sleep headbands, ensuring precise efficacy evaluation. By mimicking REM’s natural desynchronization during epileptiform-rich NREM, ADAPT-LGS offers a transformative solution to reduce seizures, improve sleep quality, and establish a paradigm shift in epilepsy management, paving the way for personalized neuromodulation therapies in catastrophic epilepsies.


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 = $1,687,906 )
2026	2026	REGENTS OF THE UNIVERSITY OF MINNESOTA	2221 UNIVERSITY AVE SE STE 100	MINNEAPOLIS	MN	55414	HENNEPIN	USA	21st Century Cures Act -Brain Research through Advancing Innovative Neurotechnologies	000	1	6/15/2026	NEW	$1,687,906
														Subtotal = $1,687,906

Grand Total All Awards = $1,687,906

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Sleep-Driven Adaptive Neuromodulation in Lennox-Gastaut Syndrome

Award Number: UH3NS145998

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 06/15/2026

PERIOD OF PERFORMANCE END DATE: 05/31/2028

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