Abstracts

Rationale: Inhibitory Deep Brain Stimulation (DBS) to suppress seizures and associated epileptogenic biomarkers is performed with high-frequency stimulation (HFS), typically between 100–165Hz, targeting the MTL where observed changes in brain rhythms, specifically in the hippocampus, include alterations in high-frequency oscillations (HFOs), namely increases in ripples and reductions in pathological Fast Ripples (FRs), and decreases in pathological interictal spikes (IRs). Recently, a new method of non-invasive DBS in epilepsy was described by us using temporal interference (TI), allowing us to focally evoke epileptiform activity in deep brain regions typically only accessible with implanted electrodes. The new work to be presented here utilizes our method of non-invasive focal TI to apply inhibitory HFS to the hippocampus of epileptic mice, suppressing epileptogenic biomarkers and pathological activity, significantly outperforming traditional transcranial stimulation (TCS). Our work represents the first completely focal and non-invasive DBS to provide therapy in epilepsy with the results widely applicable to all other deep brain regions currently treated with therapeutic stimulation.

Methods: Cohorts of epileptic mice were separated into groups to receive therapeutic stimulation using either HFS TCS (130 Hz applied from surface electrodes) or HFS TI (130 Hz envelope, f1 =1300Hz, f2=1430Hz). Parameters of the recorded IRs, and HFOs (ripples: 150-250Hz and FRs: 250-500Hz) were quantified. In all cases, HFS TI provided a remarkable reduction in epileptogentic biomarkers compared to TCS.

Results: Inhibitory DBS applied to the hippocampus has been well-characterized in animal models of epilepsy and has been demonstrated therapeutically to be very effective. The results of our non-invasive inhibitory DBS to suppress seizures and to suppress the associated epileptogenic biomarkers using focal HFS TI stimulation of the hippocampus provided very similar results to those obtained via the implantation of an invasive hippocampal electrode for similar therapeutic stimulation protocols.

Conclusions: These results constitute a first proof-of-concept for the feasibility of TI to provide focal stimulation and therapeutic benefits in epilepsy, previously only possible with invasive implanted electrodes. The data obtained and to be presented shows in detail the focal character of the electrical stimulation in the hippocampus, avoiding activation of the cortex, applied with topical electrodes to suppress pathological activity. TI could significantly change DBS in therapeutic stimulation for epilepsy, by allowing totally non-invasive deep brain exploration and stimulation to provide therapeutic relief and evaluate therapeutic targets before an invasive surgery.

Funding: Please list any funding that was received in support of this abstract.: European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No 716867).