Abstracts

Rationale: Epilepsy and sleep disruption are intimately linked: interictal epileptic discharges (IEDs) during NREM sleep exacerbate seizure risk and impair memory consolidation. Traditional antiepileptic treatments do not address sleep dysfunction, despite its significant impact on cognitive and emotional well-being. The present project targets this therapeutic gap by investigating whether non-invasive neuromodulation—specifically, Temporal Interference (TI) stimulation—can both suppress epileptiform activity and enhance deep sleep quality, offering a dual-function therapy for patients with drug-resistant epilepsy.

Methods: This study is structured into three aims. TI stimulation is applied during sleep to SEEG-implanted epilepsy patients, targeting the cortex, thalamus, and hippocampus with frequency-tuned waveforms to selectively enhance NREM3 features (slow oscillations, spindles, ripples) or suppress IEDs. Up to 30 patients receive 4 nights of stimulation (plus optional baseline/recovery nights). Combined protocols are also tested for concurrent seizure suppression and sleep enhancement. Finally, optimized TI protocols are applied to 18 non-implanted epilepsy patients using high-density EEG. All sessions use a block design (5 min ON / 5 min OFF) during stable NREM2/3. Effects are analyzed using General/Linear Mixed Models to assess electrophysiological and behavioral outcomes.

Results: Preliminary data in SEEG patients demonstrate that hippocampus-targeted TI significantly reduces IED rates for up to 24 hours post-stimulation, with no effect observed during sham. Additional data show that bilateral hippocampal TI at 1 Hz enhances biomarkers of NREM3 sleep (e.g., reduced spindle rates, decreased heart rate, and increased heart rate variability), confirming physiologic deep sleep induction. In the present study, we show that in 18 implanted epilepsy patients, combined TI stimulation protocols successfully suppress IEDs while enhancing NREM3 sleep, with measurable improvements in electrophysiological sleep quality, reduced nighttime seizure risk, and improved next-day cognitive and subjective sleep outcomes.

Conclusions: TI stimulation offers a novel, non-invasive approach to both enhance restorative sleep and reduce epileptic activity, with strong translational potential for broader clinical application. The present project is the first to systematically evaluate multi-target TI stimulation during human sleep with invasive intracranial recordings, providing mechanistic insight and a potential non-pharmacological therapy for epilepsy and sleep disruption.

Funding: This work is funded by the Czech Health Research Council and the European Reseacr Council, conducted at the International Clinical Research Center of St. Anne’s University Hospital.