Closed-loop modulation of sleep in children undergoing intracranial recordings
Children with epilepsy suffer a vicious cycle in which disturbed sleep heightens seizure susceptibility, while seizures further disrupt sleep quality, particularly impairing the slow-wave sleep (SWS) critical for cognitive, immune, and metabolic function. We present a phase-targeted auditory stimulation (PTAS) system that delivers stimuli timed to endogenous slow oscillations. In 27 children undergoing epilepsy monitoring with simultaneous scalp, intracranial, and thalamic recordings, PTAS significantly enhances SWS power, with maximal effects on thalamic, frontal, and auditory regions in a randomized cross-over protocol. Stimulation also suppresses interictal epileptiform discharges (from 0.4 to <0.1 spikes/min) and improves cognitive performance on a response inhibition task (from 76% to 95% accuracy). These results provide direct intracranial evidence that closed-loop auditory stimulation modulates sleep architecture, suppresses pathological activity, and enhances cognition. PTAS represents a physiologically informed, non-invasive approach for addressing both neurophysiological and cognitive comorbidities in pediatric epilepsy.
Authors
- Puneet Jain (ORCID: https://orcid.org/0000-0002-3320-2851)
- Olivia N. Arski (ORCID: https://orcid.org/0000-0002-7597-9765)
- H Otsubo
- Elizabeth N. Kerr (ORCID: https://orcid.org/0000-0002-9589-6502)
- Karim Mithani (ORCID: https://orcid.org/0000-0002-8094-3070)
- Nebras M. Warsi (ORCID: https://orcid.org/0000-0003-4885-3080)
- Sebastian C. Coleman (ORCID: https://orcid.org/0000-0001-7868-2839)
- Colin Massicotte (ORCID: https://orcid.org/0000-0003-4585-3739)
- Hrishikesh Suresh (ORCID: https://orcid.org/0000-0003-0412-5655)
- Alexander G. Weil (ORCID: https://orcid.org/0000-0003-4162-6096)
- Simeon M. Wong (ORCID: https://orcid.org/0000-0001-9070-0665)
- Vicki Li (ORCID: https://orcid.org/0009-0005-2091-4605)
- Ayako Ochi
- Mary Lou Smith
- Lauren Sham
- Elizabeth Donner
- Aristides Hadjinicolaou
- James T. Rutka
- Rohit Sharma
- Shelly Weiss
- George M. Ibrahim
Institutions
- University of Toronto (CA)
- Hospital for Sick Children (CA)
- Centre Hospitalier Universitaire Sainte-Justine (CA)
- Mental Health Research Canada (CA)
- SickKids Foundation (CA)
Publication Details
- Journal
- Cell Reports Medicine
- Published
- 2026-01-01
- DOI
- https://doi.org/10.1016/j.xcrm.2025.102538
- Primary Topic
- Sleep and Wakefulness Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Hospital for Sick Children
- Canadian Institutes of Health Research