Optimized phase-targeted auditory stimulation reduces nocturnal spikes in childhood epilepsies
- 1University Children's Hospital Zurich
Abstract
Interictal epileptiform discharges, so called spikes, are often strongly activated during non-rapid eye movement (NREM) sleep in childhood epilepsies. In children with pronounced spike activation during NREM - sleep, spike burden can be associated with lifelong impaired cognitive functions. This spike activation is also related to alterations in sleep oscillations, specifically slow waves and spindles, which play essential roles in brain maintenance and maturation. These observations suggest that spikes may disrupt sleep-dependent brain processes that are critical for the development of cognitive functions. Phase-targeted auditory stimulation during NREM sleep delivers brief, non-arousing tones at specific phases of ongoing slow waves to modulate sleep oscillations. Recently, our group showed that isolated, less frequent, and thus less expected, tones engage widespread thalamocortical networks, whereas repetitive, regular trains of tones promote habituation and engage more local corticocortical networks. In this study, we use these contrasting stimulation patterns for a targeted modulation of sleep oscillations and examine their interaction with epileptic spikes. In an initial exploratory study (N = 10; age range: 7.3 - 16.2 years), we used a within-night block design to directly compare responses to the different stimulation patterns. Isolated tones delivered at long interstimulus intervals induced a transient increase in spike rate, whereas down-phase stimulation delivered in trains at short, regular intervals was associated with a significant reduction. We subsequently optimized the train-based paradigm and evaluated stimulation delivered throughout the night in a proof-of-concept study using a counterbalanced, between-night design (N = 5; age range: 4.4 - 10.7 years). Spike density decreased locally in all patients, providing convergent evidence for the effects observed in the exploratory study. With this mechanistically guided approach, we demonstrate that repetitive down-phase auditory stimulation of slow waves results in a local reduction of epileptic spikes. This framework may provide a rational basis for targeted interventions aimed at reducing spikes and related cognitive impairments.
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BibTeX
@misc{schmidt2026optimized,
title = {{Optimized phase-targeted auditory stimulation reduces nocturnal spikes in childhood epilepsies}},
author = {E. C. Schmidt and N.-A. Wapp and B. Alessandri and R. Eberhard and D. Lederberger and K. Moser and L. Imbach and B. Boelsterli-Heinzle and G. Ramantani and S. Fattinger and R. Huber},
howpublished = {medRxiv},
year = {2026},
month = nov,
doi = {10.64898/2026.11.06.26367251},
url = {https://www.medrxiv.org/content/10.64898/2026.11.06.26367251v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Optimized phase-targeted auditory stimulation reduces nocturnal spikes in childhood epilepsies
AU - E. C. Schmidt
AU - N.-A. Wapp
AU - B. Alessandri
AU - R. Eberhard
AU - D. Lederberger
AU - K. Moser
AU - L. Imbach
AU - B. Boelsterli-Heinzle
AU - G. Ramantani
AU - S. Fattinger
AU - R. Huber
PY - 2026
DA - 2026/11/06
PB - medRxiv
DO - 10.64898/2026.11.06.26367251
UR - https://www.medrxiv.org/content/10.64898/2026.11.06.26367251v1
AB - Interictal epileptiform discharges, so called spikes, are often strongly activated during non-rapid eye movement (NREM) sleep in childhood epilepsies. In children with pronounced spike activation during NREM - sleep, spike burden can be associated with lifelong impaired cognitive functions. This spike activation is also related to alterations in sleep oscillations, specifically slow waves and spindles, which play essential roles in brain maintenance and maturation. These observations suggest that spikes may disrupt sleep-dependent brain processes that are critical for the development of cognitive functions. Phase-targeted auditory stimulation during NREM sleep delivers brief, non-arousing tones at specific phases of ongoing slow waves to modulate sleep oscillations. Recently, our group showed that isolated, less frequent, and thus less expected, tones engage widespread thalamocortical networks, whereas repetitive, regular trains of tones promote habituation and engage more local corticocortical networks. In this study, we use these contrasting stimulation patterns for a targeted modulation of sleep oscillations and examine their interaction with epileptic spikes. In an initial exploratory study (N = 10; age range: 7.3 - 16.2 years), we used a within-night block design to directly compare responses to the different stimulation patterns. Isolated tones delivered at long interstimulus intervals induced a transient increase in spike rate, whereas down-phase stimulation delivered in trains at short, regular intervals was associated with a significant reduction. We subsequently optimized the train-based paradigm and evaluated stimulation delivered throughout the night in a proof-of-concept study using a counterbalanced, between-night design (N = 5; age range: 4.4 - 10.7 years). Spike density decreased locally in all patients, providing convergent evidence for the effects observed in the exploratory study. With this mechanistically guided approach, we demonstrate that repetitive down-phase auditory stimulation of slow waves results in a local reduction of epileptic spikes. This framework may provide a rational basis for targeted interventions aimed at reducing spikes and related cognitive impairments.
ER -