Publication details
Non-invasive temporal interference stimulation of the hippocampus suppresses epileptic biomarkers in patients with Epilepsy: biophysical differences between kilohertz and amplitude modulated stimulation
| Authors | |
|---|---|
| Year of publication | 2026 |
| Type | Article in Periodical |
| Magazine / Source | Brain Stimulation |
| Citation | |
| web | EPI |
| Doi | https://doi.org/10.1016/j.brs.2025.11.008 |
| Keywords | Temporally interfering electric fields; Non-invasive brain stimulation; Neuromodulation; Epileptic biomarkers; sEEG; Amplitude modulation; Conduction block |
| Description | Introduction: Medication-refractory focal epilepsy creates a significant clinical challenge, with approximately 30 % of patients deemed ineligible for surgery due to involvement of eloquent cortical regions within the epileptogenic network. For these patients, electrical neuromodulation represents a promising alternative therapy. We investigated the potential of non-invasive temporal interference (TI) electrical stimulation in reducing epileptic biomarkers in patients with mesiotemporal epilepsy (MTLE) Material and method: Thirteen patients implanted with stereoelectroencephalography (sEEG) depth electrodes received TI stimulation with an amplitude modulation (AM) frequency of 130 Hz (Delta f), delivered through either low-frequency (1 kHz + 1.13 kHz) or high-frequency (9 kHz + 9.13 kHz) carrier waves, specifically targeting the hippocampus-a common epileptic focus in MTLE. Intracerebral recordings before, during, and after TI stimulation were compared to recordings during sham stimulation at varying high-frequency (HF) carrier frequencies (1, 2, 5, and 9 kHz). Results: TI stimulation resulted in a statistically significant decrease in interictal epileptiform discharges (IEDs) and pathological high-frequency oscillations (HFOs), particularly fast-ripples (FR), with prominent suppression observed in the hippocampal focus and reduced propagation brain-wide. In contrast, HF sham stimulation at 1 kHz frequency partially reduced cortical IED rates without effectively reaching the hippocampal focus. This cortical impact diminished progressively at higher sham frequencies (2, 5, and 9 kHz), exhibiting depth-dependent attenuation-a phenomenon not observed with TI stimulation, irrespective of carrier frequency. Additionally, TI stimulation demonstrated a significant carry-over effect, suppressing epileptic biomarkers beyond the stimulation period, which was not evident following kHz sham stimulation. Conclusion: Our findings underscore the therapeutic potential of TI as a non-invasive brain stimulation modality for epilepsy, offering significant suppression of epileptic biomarkers through subthreshold modulation of the epileptogenic zone. Furthermore, this study highlights distinct biophysical differences between kilohertz-frequency stimulation and focal amplitude-modulated stimulation, supporting TI's unique utility in neuromodulation research. |
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