Closed-loop modulation of sleep in children undergoing intracranial recordings.

Abstract

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.