Non-invasive temporal interference stimulation of the
hippocampus suppresses epileptic biomarkers in patients with
Epilepsy: biophysical differences between kilohertz and
amplitude modulated stimulation

J 2026

Non-invasive temporal interference stimulation of the hippocampus suppresses epileptic biomarkers in patients with Epilepsy: biophysical differences between kilohertz and amplitude modulated stimulation

MISSEY, Florian; Emma ACERBO; Adam S DICKEY; Jan TRAJLINEK; Ondrej STUDNICKA et al.

Základní údaje

Originální název

Non-invasive temporal interference stimulation of the hippocampus suppresses epileptic biomarkers in patients with Epilepsy: biophysical differences between kilohertz and amplitude modulated stimulation

Autoři

Vydání

Brain Stimulation, NEW YORK, ELSEVIER SCIENCE INC, 2026, 1935-861X

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30230 Other clinical medicine subjects

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

EPI

Impakt faktor

Impact factor: 8.400 v roce 2024

Organizační jednotka

CZECRIN IV

DOI

https://doi.org/10.1016/j.brs.2025.11.008

UT WoS

001630415300002

Klíčová slova česky

Temporally interfering electric fields; Non-invasive brain stimulation; Neuromodulation; Epileptic biomarkers; sEEG; Amplitude modulation; Conduction block

Klíčová slova anglicky

Temporally interfering electric fields; Non-invasive brain stimulation; Neuromodulation; Epileptic biomarkers; sEEG; Amplitude modulation; Conduction block

Štítky

CZECRIN, Excelence Science, FNUSA, RIV, user

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 27. 1. 2026 13:53, Mgr. Eva Suchánková

Anotace

V originále

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 (Delta f), 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. Conclusion: 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.

Návaznosti

MUNI/A/1683/2024, interní kód MU

Název: From preclinical to clinical research

Investor: Masarykova univerzita, From preclinical to clinical research

90249, velká výzkumná infrastruktura

Název: CZECRIN IV

Citovat

MISSEY, Florian; Emma ACERBO; Adam S DICKEY; Jan TRAJLINEK; Ondrej STUDNICKA; Claudia LUBRANO; Mariane DE ARAUJO E SILVA; Evan BRADY; Vit VSIANSKY; Johanna SZABO; Irena DOLEZALOVA; Daniel FABO; Martin PAIL; Claire-Anne GUTEKUNST; Rosanna MIGLIORE; Michele MIGLIORE; Stanislas LAGARDE; Romain CARRON; Fariba KARIMI; Raul Castillo ASTORGA; Antonino M CASSARA; Niels KUSTER; Esra NEUFELD; Fabrice BARTOLOMEI; Nigel P PEDERSEN; Robert E GROSS; Viktor JIRSA; Daniel L DRANE; Milan BRÁZDIL a Adam WILLIAMSON. 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. NEW YORK: ELSEVIER SCIENCE INC, 2026, roč. 19, č. 1, s. 1-12. ISSN 1935-861X. Dostupné z: https://doi.org/10.1016/j.brs.2025.11.008.

@article{2547429,
   author = {Missey, Florian and Acerbo, Emma and Dickey, Adam S and Trajlinek, Jan and Studnicka, Ondrej and Lubrano, Claudia and de Araujo e Silva, Mariane and Brady, Evan and Vsiansky, Vit and Szabo, Johanna and Dolezalova, Irena and Fabo, Daniel and Pail, Martin and Gutekunst, ClaireandAnne and Migliore, Rosanna and Migliore, Michele and Lagarde, Stanislas and Carron, Romain and Karimi, Fariba and Astorga, Raul Castillo and Cassara, Antonino M and Kuster, Niels and Neufeld, Esra and Bartolomei, Fabrice and Pedersen, Nigel P and Gross, Robert E and Jirsa, Viktor and Drane, Daniel L and Brázdil, Milan and Williamson, Adam},
   article_location = {NEW YORK},
   article_number = {1},
   doi = {https://doi.org/10.1016/j.brs.2025.11.008},
   keywords = {Temporally interfering electric fields; Non-invasive brain stimulation; Neuromodulation; Epileptic biomarkers; sEEG; Amplitude modulation; Conduction block},
   language = {eng},
   issn = {1935-861X},
   journal = {Brain Stimulation},
   title = {Non-invasive temporal interference stimulation of the hippocampus suppresses epileptic biomarkers in patients with Epilepsy: biophysical differences between kilohertz and amplitude modulated stimulation},
   url = {https://www.sciencedirect.com/science/article/pii/S1935861X25003791?pes=vor&utm_source=clarivate&getft_integrator=clarivate},
   volume = {19},
   year = {2026}
}

TY  - JOUR
ID  - 2547429
AU  - Missey, Florian - Acerbo, Emma - Dickey, Adam S - Trajlinek, Jan - Studnicka, Ondrej - Lubrano, Claudia - de Araujo e Silva, Mariane - Brady, Evan - Vsiansky, Vit - Szabo, Johanna - Dolezalova, Irena - Fabo, Daniel - Pail, Martin - Gutekunst, Claire-Anne - Migliore, Rosanna - Migliore, Michele - Lagarde, Stanislas - Carron, Romain - Karimi, Fariba - Astorga, Raul Castillo - Cassara, Antonino M - Kuster, Niels - Neufeld, Esra - Bartolomei, Fabrice - Pedersen, Nigel P - Gross, Robert E - Jirsa, Viktor - Drane, Daniel L - Brázdil, Milan - Williamson, Adam
PY  - 2026
TI  - Non-invasive temporal interference stimulation of the hippocampus suppresses epileptic biomarkers in patients with Epilepsy: biophysical differences between kilohertz and amplitude modulated stimulation
JF  - Brain Stimulation
VL  - 19
IS  - 1
SP  - 1-12
EP  - 1-12
PB  - ELSEVIER SCIENCE INC
SN  - 1935861X
KW  - Temporally interfering electric fields
KW  - Non-invasive brain stimulation
KW  - Neuromodulation
KW  - Epileptic biomarkers
KW  - sEEG
KW  - Amplitude modulation
KW  - Conduction block
UR  - https://www.sciencedirect.com/science/article/pii/S1935861X25003791?pes=vor&utm_source=clarivate&getft_integrator=clarivate
N2  - 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 (Delta f), 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. Conclusion: 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.
ER  -

MISSEY, Florian; Emma ACERBO; Adam S DICKEY; Jan TRAJLINEK; Ondrej STUDNICKA; Claudia LUBRANO; Mariane DE ARAUJO E SILVA; Evan BRADY; Vit VSIANSKY; Johanna SZABO; Irena DOLEZALOVA; Daniel FABO; Martin PAIL; Claire-Anne GUTEKUNST; Rosanna MIGLIORE; Michele MIGLIORE; Stanislas LAGARDE; Romain CARRON; Fariba KARIMI; Raul Castillo ASTORGA; Antonino M CASSARA; Niels KUSTER; Esra NEUFELD; Fabrice BARTOLOMEI; Nigel P PEDERSEN; Robert E GROSS; Viktor JIRSA; Daniel L DRANE; Milan BRÁZDIL a Adam WILLIAMSON. Non-invasive temporal interference stimulation of the hippocampus suppresses epileptic biomarkers in patients with Epilepsy: biophysical differences between kilohertz and amplitude modulated stimulation. \textit{Brain Stimulation}. NEW YORK: ELSEVIER SCIENCE INC, 2026, roč.~19, č.~1, s.~1-12. ISSN~1935-861X. Dostupné z: https://doi.org/10.1016/j.brs.2025.11.008.

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