Closed-Loop Acoustic Stimulation During Sleep in Children With Epilepsy: A Hypothesis-Driven Novel Approach to Interact With Spike-Wave Activity and Pilot Data Assessing Feasibility

Slow waves, the electroencephalographic (EEG) hallmark of deep sleep, can be systematically manipulated by acoustic stimulation: stimulation time-locked to the down phase of slow waves reduces, whereas stimulation time-locked to the up phase increases slow waves. Spike-waves during sleep seem to be related to slow waves, raising the question of whether spike-waves can be systematically influenced by such acoustic stimulation. In five pediatric patients, all-night EEG was recorded, combined with real-time slow wave detection. Throughout the night, acoustic stimulation was performed in a 3 x 5-min-block design (no stimulation-stimulation-no stimulation). Tones were applied time-locked either to the up or to the down phase of the detected slow waves in an alternating pattern. All patients tolerated the acoustic stimulation during sleep well. They showed high sleep quality and no signs of clinical or non-convulsive electrographic seizures. Our preliminary analysis shows no systematic effect of acoustic stimulation on spike-wave activity. Moreover, with our stimulation approach tones were distributed over a rather broad phase-range during the DOWN or UP stimulation and showed inter-individual differences in their distribution. In this study, we applied for the first time an acoustic closed-loop slow wave stimulation tool for a non-invasive manipulation of spike-wave activity. Thus, our pilot data show that closed-loop acoustic stimulation is feasible and well tolerated in children with spike wave activity during sleep. Improved precision in phase targeting and personalized stimulation parameters in a larger sample of subjects might be needed to show systematic effects.