Authors :
Presenting Author: Raul Castillo-Astorga, MD – University of California Davis
Florian Missey, PhD – St. Anne's University Hospital Brno
Claudia LUBRANO, PhD – St. Anne's University Hospital Brno
Ondrej STUDNICKA, BS – St. Anne's University Hospital Brno
Emma ACERBO, PhD – EMORY University
Daniel Drane, PhD – Emory University
Adam Williamson, PhD – St. Anne's University Hospital Brno
Nigel Pedersen, MBBS – UC Davis
Rationale: Epilepsy is a prevalent neurological disorder affecting approximately 1% of the global population
(Zack 2017). About one-third of patients are unresponsive to anti-seizure medications and many others have side-effects. Only select patients are candidates for surgery, and outcomes of neuromodulation and resection range from no response to 70% cure in the best of cases
(Ryvlin, Helen Cross, and Rheims 2014). New technologies and approaches to treatment are needed. Invasive stimulation approaches that target cerebral cortex or subcortical forebrain structures have shown some benefits, but all surgical approaches to treatment are invasive and have important associated morbidity.
We propose to use a novel non-invasive temporally interfering electric field (TIEF) stimulation as a candidate therapy. This approach can modulate a focal or larger tissue area than conventional deep brain stimulation at any location in the forebrain, is completely non-invasive, and is easily reconfigured. This approach could have a transformative impact on the treatment of epilepsy. TIEF is a technique that works by overlapping two or more ‘carrier’ high-frequency fields (≥2 kHz) that do not impact neural tissues, while creating a new low-frequency target ‘envelope’ field that modulates neural activity
(Grossman et al. 2017). It has been shown to be safe and produce changes in hippocampal activity and memory performance in humans
(Violante et al. 2023). This will be the first time that TIEF is used to suppress epileptiform activity and will be validated using the gold standard of stereo-electroencephalography (sEEG).
Methods: Patients undergoing intracranial sEEG studies with refractory focal epilepsy will receive sham (aligned carrier frequencies, thus not creating an envelope) versus active (interference stimulation) in random order. Inhibitory TI will be administered by two carrier frequencies, creating an envelope frequency of 150 Hz, targeted in an individualized manner to the suspected epileptogenic structure. Aim I. TIEF to reduce epileptic activity (interictal discharges) in the seizure onset zone. We hypothesize that focal inhibitory TIEF stimulation will reduce epileptiform spontaneous hippocampal discharges. Aim II. TIEF to Suppress Electrical-Stimulation-Induced Seizures and Evoked After-Discharges. Independent of Aim I, we will examine the hypothesis that TIEF stimulation at a site of putative seizure onset can prevent or raise the threshold to seizures, and reduce the frequency of electrically evoked after-discharges.
Results:
TIEF can efficiently reduce epileptic biomarkers (interictal discharges) in patients (Pre-TIEF vs TIEF p-value < 0.001, Pre-TIEF vs Post-TIEF p-value=0.27, TIEF vs Post-TIEF p-value =0.001, n=1).Conclusions:
This research proposes a new non-invasive and drugless therapeutic approach for patients with focal epilepsy. The implications of this study could extend beyond epilepsy; given the depth and focality advantages of TI, it stands as a promising candidate for non-invasively stimulating deeper central nervous system structures.Funding: NPP is supported by CURE Epilepsy, K08NS105929, and R21NS122011. RCA is supported by the Chilean-American Fulbright Commission.