Evidence map›Paper›PMID 41232758›Full record

ArticleBrain stimulation

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

Florian Missey, Emma Acerbo, Adam S Dickey, Jan Trajlinek, Ondřej Studnička, Claudia Lubrano, Mariane de Araújo E Silva, Evan Brady, Vit Všianský, Johanna Szabo and 20 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Brain stimulation. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

22 citing papers in PubMed.

  1. Trial
  2. Trial
  3. Trial
  4. Review
  5. Article
  6. Article
  7. Review
  8. Review
  9. Article
  10. Article
  11. Article
  12. Review
  13. Review
  14. Article
  15. Article
  16. Article
  17. Virtual brain twins for stimulation in epilepsy.Nature computational science · 2025
    Article
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

30 authors.

Florian MisseyInternational Clinical Research Center, St. Anne's University Hospital Brno, 60200, Brno, Czech Republic; Aix-Marseille Université, Inserm, Institut de Neurosciences des Systèmes (INS) UMR_S 1106, Marseille, France.
Emma AcerboDepartment of Neurosurgery, Emory University School of Medicine, Atlanta, GA, USA; Department of Neurology, Emory University School of Medicine, Atlanta, GA, USA.
Adam S DickeyDepartment of Neurology, Emory University School of Medicine, Atlanta, GA, USA.
Jan TrajlinekInternational Clinical Research Center, St. Anne's University Hospital Brno, 60200, Brno, Czech Republic.
Ondřej StudničkaInternational Clinical Research Center, St. Anne's University Hospital Brno, 60200, Brno, Czech Republic.
Claudia LubranoInternational Clinical Research Center, St. Anne's University Hospital Brno, 60200, Brno, Czech Republic.
Mariane de Araújo E SilvaInternational Clinical Research Center, St. Anne's University Hospital Brno, 60200, Brno, Czech Republic.
Evan BradyDepartment of Neurology, Emory University School of Medicine, Atlanta, GA, USA.
Vit VšianskýBrno Epilepsy Center, 1st Department of Neurology, St. Anne's Univ. Hospital and Faculty of Medicine, Masaryk University, member of the ERN EpiCARE, 60200, Brno, Czech Republic.
Johanna SzaboInstitute of Neurosurgery and Neurointervention, Semmelweis University, Budapest, Hungary.
Irena DolezalovaBrno Epilepsy Center, 1st Department of Neurology, St. Anne's Univ. Hospital and Faculty of Medicine, Masaryk University, member of the ERN EpiCARE, 60200, Brno, Czech Republic.
Daniel FaboInstitute of Neurosurgery and Neurointervention, Semmelweis University, Budapest, Hungary.
Martin PailBrno Epilepsy Center, 1st Department of Neurology, St. Anne's Univ. Hospital and Faculty of Medicine, Masaryk University, member of the ERN EpiCARE, 60200, Brno, Czech Republic.
Claire-Anne GutekunstDepartment of Neurosurgery, Emory University School of Medicine, Atlanta, GA, USA.
Rosanna MiglioreInstitute of Biophysics, National Research Council, Palermo, Italy.
Michele MiglioreInstitute of Biophysics, National Research Council, Palermo, Italy; SUNY Dept. of Neurology, Downstate Health Science University, Brooklyn, NY, USA.
Stanislas LagardeAix-Marseille Université, Inserm, Institut de Neurosciences des Systèmes (INS) UMR_S 1106, Marseille, France; APHM, Timone Hospital, Epileptology Department, Marseille, France.
Romain CarronAix-Marseille Université, Inserm, Institut de Neurosciences des Systèmes (INS) UMR_S 1106, Marseille, France; Department of Functional and Stereotactic Neurosurgery, Timone University Hospital, Marseille, France.
Fariba KarimiFoundation for Research on Information Technologies in Society (IT'IS), Zurich, Switzerland.
Raul Castillo AstorgaDepartment of Neurology, School of Medicine and Center for Neuroscience, University of California, Davis, CA, USA.
Antonino M CassaraFoundation for Research on Information Technologies in Society (IT'IS), Zurich, Switzerland.
Niels KusterFoundation for Research on Information Technologies in Society (IT'IS), Zurich, Switzerland; Department of Information Technology and Electrical Engineering, Swiss Federal Institute of Technology (ETH), Zurich, Switzerland.
Esra NeufeldFoundation for Research on Information Technologies in Society (IT'IS), Zurich, Switzerland.
Fabrice BartolomeiAix-Marseille Université, Inserm, Institut de Neurosciences des Systèmes (INS) UMR_S 1106, Marseille, France; APHM, Timone Hospital, Epileptology Department, Marseille, France.
Nigel P PedersenDepartment of Neurology, School of Medicine and Center for Neuroscience, University of California, Davis, CA, USA.
Robert E GrossDepartment of Neurosurgery, Emory University School of Medicine, Atlanta, GA, USA; Department of Neurosurgery, New Jersey Medical School and Robert Wood Johnson Medical School, Rutgers University, New Jersey, USA.
Viktor JirsaAix-Marseille Université, Inserm, Institut de Neurosciences des Systèmes (INS) UMR_S 1106, Marseille, France.
Daniel L DraneDepartment of Neurology, Emory University School of Medicine, Atlanta, GA, USA; Departments of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA; Department of Neurology, University of Washington School of Medicine, Seattle, WA, USA.
Milan BrázdilBrno Epilepsy Center, 1st Department of Neurology, St. Anne's Univ. Hospital and Faculty of Medicine, Masaryk University, member of the ERN EpiCARE, 60200, Brno, Czech Republic.
Adam WilliamsonInternational Clinical Research Center, St. Anne's University Hospital Brno, 60200, Brno, Czech Republic; Center for Social and Affective Neuroscience, Department of Biomedical and Clinical Sciences, Linköping University, Sweden. Electronic address: adam.williamson@fnusa.cz.

Funding

Investigations of Spatial Recognition Memory to Improve Cognitive Outcomes in Epilepsy SurgeryR01NS144894 · NINDS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI Nigel Paul Pedersen · 2025 to 2026
$1.3M
Control of the Hippocampal Formation by the Supramammillary Hypothalamus - Anatomy, Physiology and in a Model of Medial Temporal Lobe EpilepsyK08NS105929 · NINDS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI PEDERSEN, NIGEL PAUL · 2018 to 2023
$963k
NINDS NIH HHS K08 NS105929NINDS NIH HHS R01 NS144894
6 · The paper itself

Abstract

introductionMedication-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

methodThirteen 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).

resultsTI 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.

conclusionOur 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.

Indexed as

Deep Brain StimulationDrug Resistant EpilepsyEpilepsy, Temporal LobeHippocampusAdultBiomarkersElectrodes, ImplantedElectroencephalographyFemaleHumansMaleMiddle AgedYoung AdultBiomarkersAmplitude modulationConduction blockEpileptic biomarkersNeuromodulationNon-invasive brain stimulationsEEGTemporally interfering electric fields

Identifiers

PMID41232758
PMCPMC12858428

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.