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Non-vectorial integration of intersectional short-pulse stimulation enables enhanced deep brain modulation and effective seizure control.

Overview

Authors: Tamás Földi1,2,3, Miklos Szoboszlay2, Zoltán Chadaide1,2, Bence Radics4, Bálint Horváth2, Endre Vecsernyés2, István Langó2, Péter Ráfi1,2, Andrea Pejin1,2, Lívia Barcsai1,2,3, Gábor Kozák1,5, Nóra Forgó1,2,3, Kristóf Furuglyás2, Olivér Nagy6, Anett J. Nagy1,2,3, Tamás Laszlovszky2, Zoltán Somogyvári2,7, Magor L. Lőrincz1,6,8, Orrin Devinsky9, Antal Berényi1,2,3,10
ORCID iDs: Tamás Földi, Miklos Szoboszlay, Bálint Horváth, Lívia Barcsai, Gábor Kozák, Olivér Nagy, Magor L. Lőrincz, Orrin Devinsky, Antal Berényi
  1. MTA-SZTE ‘Momentum’ Oscillatory Neuronal Networks Research Group, Department of Physiology, University of Szeged,Szeged, Hungary
  2. Neunos ZRt, Szeged, Hungary
  3. HCEMM-SZTE Magnetotherapeutics Research Group, University of Szeged,Szeged, Hungary
  4. Department of Pathology, University of Szeged,Szeged, Hungary
  5. Department of Neurology & Stroke, University of Tübingen, Tübingen, Baden-Württemberg, Germany; Hertie-Institute for Clinical Brain Research,Tübingen, Baden-Württemberg Germany
  6. Department of Physiology, Anatomy and Neuroscience, Faculty of Sciences University of Szeged,Szeged, Hungary
  7. Department of Computational Sciences, HUN-REN Wigner Research Centre for Physics,Budapest, Hungary
  8. Neuroscience Division, Cardiff University,Museum Avenue Cardiff, UK
  9. Department of Neurology, NYU Langone Comprehensive Epilepsy Center, NYU Grossman School of Medicine,New York, NY USA
  10. Neuroscience Institute, New York University,New York, NY USA
Institutions: University of Szeged (Hungary); Hertie Institute for Clinical Brain Research (Germany); HUN-REN Wigner Research Centre for Physics (Hungary); Cardiff University (United Kingdom); New York University (United States)
Journal: Communications medicine, volume 6, issue 1, article 353
Dates: received 6 February 2025; accepted 7 April 2026; published online 21 April 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1038/s43856-026-01595-6 · PMID 42014476 · PMCID PMC13287739 · OpenAlex W4406127723
Open access: gold, a free copy (OpenAlex)
Preprint: doi:10.1101/2025.01.02.631064
Status: code verified
Categories: intracellular / patch clamp (modality), rat (organism), epilepsy (population)
Methods: Spectral & time-frequency, Statistics, Preprocessing, Smoothing, state filtering, decompositions, Physiology & signal measures
Keywords: Membrane potential, Excitability, Network models
Topic: Transcranial Magnetic Stimulation Studies (Neurology, Neuroscience), according to OpenAlex
Funding: Hungarian Scientific Research Fund (TKP2021-EGA, TKP2021-EGA-28, FK123831, K135837, TKP2021, 739593, EFOP-3.6.1-16-2016-00008, NN125601); Magyar Tudományos Akadémia (TKP2021-EGA, 20391-3/2018/FEKUSTRAT, TKP2021, EFOP-3.6.1-16-2016-00008, KKP133871/KKP20, 739593, TKP2021-EGA-28); Emberi Eroforrások Minisztériuma (EFOP-3.6.1-16-2016-00008, 739593, 20391‐3/2018/FEKUSTRAT, TKP2021-EGA-28, 20391-3/2018); National Research, Development and Innovation Office (20391-3/2018/FEKUSTRAT, TKP2021-EGA-28, TKP-2021-EGA, K135837, EFOP-3.6.1-16-2016-00008, 739 593, TKP 2021)
Citations: not cited yet (Europe PMC); 76 references in the paper
Research resources: RRID:SCR_001622, RRID:SCR_002455

Abstract

Background: Transcranial electrical stimulation (TES) has limited spatial focus and depth penetration, constraining its therapeutic efficacy. Intersectional Short-Pulse (ISP) stimulation was developed to overcome these limitations by delivering rapidly switching pulses that can be temporally integrated by neuronal membranes. Here, we aimed to establish the biophysical basis of ISP-induced temporal summation and to test whether this mechanism enables effective brain modulation in vivo.

Methods: We combined finite-element modeling, cadaver measurements (n = 2 human cadavers), and biophysically realistic NEURON simulations to characterize the spatial and temporal properties of ISP-induced electric fields. In vivo whole-cell patch-clamp recordings were performed in the rat somatosensory cortex (female Wistar rat) to test the membrane-level integration of sequential electric field pulses. Functional efficacy was evaluated using closed-loop ISP stimulation in a hippocampal kindling model of temporal lobe epilepsy in male Long–Evans rats (n = 11 animals, >500 induced seizures analyzed across conditions).

Results: Here we show that neurons integrate sequential ISP pulses in a non-vectorial, temporally accumulative manner, consistent with membrane-level charge integration rather than extracellular field superposition. ISP and conventional TES simulations produced similar instantaneous field magnitudes, but ISP stimulation resulted in more uniform neuronal excitability across brain depths. Closed-loop ISP stimulation significantly outperformed conventional TES in reducing seizure duration and severity. ISP reduced hippocampal seizure duration by 45% and 35% compared to SHAM stimulation and conventional TES, and significantly reduced motor seizure severity.

Conclusions: ISP stimulation provides a non-invasive neuromodulation approach that enhances deep brain engagement through rapid, temporally structured pulse sequences. These findings demonstrate effective seizure suppression in a rodent model and support the translational potential of ISP for disorders involving pathological neural dynamics.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

No file of the authors' code could be read here: it is described below, and read at its source.

pypi.org/project/pyabf

License: none: the authors keep all their rights
State: the link answers, verified on 29 September 2026
Evidence: the link answers
Software Heritage: not checked
Found in: the text, “In vivo whole-cell patch-clamp recordings with c”
Not found: README, license file, CITATION.cff, environment file, tests, continuous integration, documentation
Availability: 1 check, the latest on 29 September 2026: the link answers (HTTP 200)
  • 29 September 2026: the link answers (HTTP 200)
At the source: pypi.org/project/pyabf/

Code availability

All custom codes are freely available from the corresponding author on reasonable request.

Reproduced under the paper's license (CC BY), from the paper cited above.

Tracing map

Proposed by the machine: these links were found in the paper and verified at the source, without human review. The map will receive a Zenodo DOI once one of the paper's authors has validated it with their ORCID.

What the map holds:

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Data

No dataset and no data link were found in the paper.

Data availability

The data generated in this study are available from the corresponding author upon reasonable request. The numerical results underlying the graphs and charts presented in the main figures are available in Supplementary Data 1.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 29 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 20 authors, 3 keywords, 4 funders, 75 references, 2 RRIDs.

Cite

This paper

Földi, T., Szoboszlay, M., Chadaide, Z., Radics, B., Horváth, B., Vecsernyés, E., Langó, I., Ráfi, P., Pejin, A., Barcsai, L., Kozák, G., Forgó, N., Furuglyás, K., Nagy, O., Nagy, A. J., Laszlovszky, T., Somogyvári, Z., Lőrincz, M. L., Devinsky, O., & Berényi, A. (2026). Non-vectorial integration of intersectional short-pulse stimulation enables enhanced deep brain modulation and effective seizure control. Communications medicine, 6(1), 353. https://doi.org/10.1038/s43856-026-01595-6

BibTeX

@article{foldi2026non,
author = {Földi, Tamás and Szoboszlay, Miklos and Chadaide, Zoltán and Radics, Bence and Horváth, Bálint and Vecsernyés, Endre and Langó, István and Ráfi, Péter and Pejin, Andrea and Barcsai, Lívia and Kozák, Gábor and Forgó, Nóra and Furuglyás, Kristóf and Nagy, Olivér and Nagy, Anett J. and Laszlovszky, Tamás and Somogyvári, Zoltán and Lőrincz, Magor L. and Devinsky, Orrin and Berényi, Antal},
title = {{Non-vectorial integration of intersectional short-pulse stimulation enables enhanced deep brain modulation and effective seizure control}},
journal = {Communications medicine},
year = {2026},
month = apr,
volume = {6},
number = {1},
pages = {353},
publisher = {Nature Publishing Group},
issn = {2730-664X},
doi = {10.1038/s43856-026-01595-6},
url = {https://doi.org/10.1038/s43856-026-01595-6},
pmid = {42014476},
pmcid = {PMC13287739}
}

RIS

TY - JOUR
AU - Földi, Tamás
AU - Szoboszlay, Miklos
AU - Chadaide, Zoltán
AU - Radics, Bence
AU - Horváth, Bálint
AU - Vecsernyés, Endre
AU - Langó, István
AU - Ráfi, Péter
AU - Pejin, Andrea
AU - Barcsai, Lívia
AU - Kozák, Gábor
AU - Forgó, Nóra
AU - Furuglyás, Kristóf
AU - Nagy, Olivér
AU - Nagy, Anett J.
AU - Laszlovszky, Tamás
AU - Somogyvári, Zoltán
AU - Lőrincz, Magor L.
AU - Devinsky, Orrin
AU - Berényi, Antal
TI - Non-vectorial integration of intersectional short-pulse stimulation enables enhanced deep brain modulation and effective seizure control
T2 - Communications medicine
J2 - Commun Med (Lond)
PY - 2026
DA - 2026/04/21
VL - 6
IS - 1
SP - 353
SN - 2730-664X
PB - Nature Publishing Group
DO - 10.1038/s43856-026-01595-6
UR - https://doi.org/10.1038/s43856-026-01595-6
LA - en
ER -

CSL-JSON

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