Temporal Interference Stimulation

New Research Study Identifies Potential Benefits for Epilepsy Patients

We have previously published blog articles highlighting use of Digitimer DS5 Isolated Bipolar Stimulators to deliver transcranial Temporal Interference Stimulation (TIS), a novel electrical stimulation technique first postulated and demonstrated pre-clinically by Nir Grossman in 2017.  Grossman and colleagues proposed that TIS could have potential value as a non-invasive alternative to traditional deep brain stimulation methods that are currently used to treat conditions including epilepsy, tremor and Parkinson’s disease.  Today, there is a global interest in TIS with researchers not only investigating potential therapeutic targets, but also refining protocols for safe but efficacious stimulus delivery.

TI stimulation is a form of electrical stimulation that relies on the delivery of high-frequency (typically >1kHz) electrical stimulation from two current sources.  Ordinarily, stimulation at such high frequencies does not result in the recruitment of neuronal firing, however, if the two stimulation sources produce waveforms with frequencies that differ by a small amount, they will generate an interference envelope that “beats” at a lower frequency.  This will activate underlying neurons in the location where the two stimulus waveforms intersect.  Using MRI scans, stimulation simulations and software planning tools, standard transcutaneous electrodes can be precisely positioned on the surface of the scalp to optimise targeted temporal interference stimulation for a particular brain region.

Here we present a recent TIS paper published in the journal Brain Stimulation by lead authors Florian Missey & Emma Acerbo.  Working with a team collaborators from high-profile institutes across Europe and the USA, they have demonstrated a suppression of epileptic biomarkers in mesiotemporal epilepsy patients receiving TIS of the hippocampus.  Using pairs of Digitimer DS5’s as their chosen isolated current stimulation sources, this clinical trial not only demonstrated a significant reduction in epilepsy biomarkers, but also highlighted biophysical differences between kHz stimulation and the focal amplitude-modulated stimulation provided by TIS.

We include the abstract so as to give you an overview of their study and their findings, but the full paper is available to read here.

Missey F, Acerbo E, Dickey A …  Non-invasive temporal interference stimulation of the hippocampus suppresses epileptic biomarkers in patients with Epilepsy: biophysical differences between kilohertz and amplitude modulated stimulation  Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation, 2025; 19

Abstract

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 (Δf), 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.

Conclusions

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.