Epilepsy poses a significant neurological challenge, with approximately 30% of patients ineligible for surgery due to involvement of eloquent brain regions in the epileptogenic zone. Electrical stimulation (such as Deep Brain Stimulation) represents a promising alternative therapy. In this study, we investigate the therapeutic potential of Temporally Interfering (TI) electric fields on people with epilepsy through intracranial recordings. Thirteen patients implanted with depth electrodes, specifically stereoelectroencephalography (SEEG) electrodes, were subjected to TI stimulation (centered at 1.3kHz, 7kHz and 9kHz with an offset frequency of 130Hz), targeting deep brain areas associated with epilepsy, here the mesial temporal lobe (hippocampal region). Our results reveal an average decrease of 60% in the total number of interictal epileptiform discharges (IEDs) across the brain, indicative of the efficacy of TI in modulating epileptic biomarkers. Additionally, sham stimulation at 1kHz frequency demonstrated an impact on IEDs activity; however, this effect was diminished with increased sham frequencies (at 5 and 9kHz), highlighting the selective effectiveness of TI in influencing epileptic biomarkers. Our findings underscore the potential of TI stimulation as a promising therapeutic intervention for epilepsy, offering insights into its precise modulation of brain oscillations and its utility in managing drug-resistant forms of epilepsy. Clinical Trial Number NCT06716866.

N.K. and E.N. are shareholders of TI Solutions AG, a company dedicated to producing temporal interference (TI) stimulation devices to support TI research.

NCT06716866

A.W. received funding from the European Union s Horizon Europe research and innovation programme under grant agreement No. 101101040 (TREATMENT) and No. 101088623 (EMUNITI). Effort on this project for both Drs. Daniel Drane and Emma Acerbo were in part supported by grants received from the National institute of Neurological Disorders and Stroke (NINDS) of the National Institutes of Healthy (NIH) [R01NS088748]. Emma Acerbo was also supported through the Emory Neuromodulation Technology Innovation Center (ENTICe).

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The Emory IRB of Emory University, Atlanta, GA, USA gave ethical approval for this work under the number IRB00099109. The ethical committee of St. Anne's University Hospital Brno, Brno, Czech Republic gave ethical approval for this work under the number IIT/2023/25. The ethical committee of the Institute of Neurosurgery and Neurointervention, Semmelweis University, Budapest, Hungary gave ethical approval for this work under the number OGYEI/56526-2/2023. All experiments were conducted after a clinical trial registration and agreement (NCT06716866).

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All data produced in the present study are available upon reasonable request to the authors.