Aug 19, 2022

Focal Non-Invasive Deep-Brain Stimulation with Temporal Interference for the Suppression of Epileptic Biomarkers

Emma Acerbo, Aude Jegou, Charlotte Luff, Patrycja Dzialecka, Boris Botzanowski, Florian Missey, Ibrahima Ngom, Stanislas Lagarde, Fabrice Bartolomei, Antonino Cassara, Esra Neufeld, Viktor Jirsa, Romain Carron, Nir Grossman, and Adam Williamson, Frontiers in Neuroscience 2022, Volume 16, Article No. 945221, online 17 August 2022; doi: 10.3389/fnins.2022.945221

Neurostimulation applied with deep brain stimulation (DBS) electrodes is an effective therapeutic intervention in patients suffering from intractable drug-resistant epilepsy for whom resective surgery is contraindicated or has failed. Inhibitory DBS to suppress seizures and associated epileptogenic biomarkers could be performed with high-frequency stimulation (HFS), at frequencies typically between 100 and 165 Hz, to various deep-seated targets, such as the mesio-temporal lobe (MTL), which leads to changes in brain rhythms, specifically in the hippocampus. The most prominent changes include increases in high-frequency oscillations (HFOs), i.e., increases in ripples, reductions in pathological fast ripples (FRs), and decreases in pathological interictal epileptiform discharges (IEDs). To demonstrate the potential efficiency of temporal interference (TI) stimulation to provide non-invasive DBS of the hippocampus at a frequency of 130 Hz, TI experiments were executed in mouse models of epilepsy and on human cadavers. Simulations for both mice and human heads were performed to determine the best coordinates to use to reach the hippocampus. It was found that TI stimulation increases physiological ripples, decreases the number of FRs and IEDs in the hippocampus in a mouse model of epilepsy, and that transcranial current stimulation (TCS) performed at 130 Hz fails to achieve similar results. Further, the translatability of TI stimulation for use in human subjects was demonstrated via measurements of the TI stimulation vs. TCS in human cadavers.

The scientific and technical impact of the study can be summarized as:

  • The findings demonstrate, through stereoelectroencephalography (sEEG) measurements and functional responses, the feasibility and efficiency of TI to preferentially stimulate an area at depth while avoiding exposure of overlying tissues
  • TI can successfully stimulate the hippocampus where TCS fails to do so
  • TI is a non-invasive approach that might be of diagnostic and/or therapeutic value to epilepsy patients
  • Further studies are needed to investigate potential performance and safety aspects of DBS by non-invasive TI