Aberrant neural activity in the peritumoral cortex underlies the progression of tumor-associated seizures

Seizures are frequent complications in brain tumor patients, yet the underlying neuronal mechanisms remain poorly defined. Here, we examined pathophysiological alterations in the peritumoral cortex of patients undergoing tumor resection. The synaptic activity, dendritic spine density, and gene expression of peritumoral pyramidal neurons differed significantly between patients with and without seizures. Using an inducible glioma rodent model, we characterized the progression of these alterations and their predictive value for seizure initiation. Computational simulations revealed that human cortical neurons are highly susceptible to synaptic and dendritic perturbations, which induce paroxysmal depolarizing shifts (PDS) in affected networks. Longitudinal analyses post-surgery showed that PDS were detectable prior to seizure onset in a subset of patients and reliably predicted post-resection seizure occurrence. These findings elucidate key neuronal substrates of tumor-associated seizures and suggest PDS as a potential biomarker for seizure risk, offering a foundation for targeted diagnostic and therapeutic strategies.

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Publication Details

Journal
Nature Communications
Published
2025-12-02
DOI
https://doi.org/10.1038/s41467-025-66226-5
Primary Topic
Neuroscience and Neuropharmacology Research
Type
article
Field-Weighted Citation Impact
0.00

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article

Aberrant neural activity in the peritumoral cortex underlies the progression of tumor-associated seizures

Jian K. Liu, Arnaud J.P.E. Vincent, Bibi L. J. Bouwen, Zhenyu Gao et al.
Nature Communications
Neuroscience and Neuropharmacology Research
article

Aberrant neural activity in the peritumoral cortex underlies the progression of tumor-associated seizures

Jian K. Liu, Arnaud J.P.E. Vincent, Bibi L. J. Bouwen, Zhenyu Gao, Vera van Dis, Chris I. De Zeeuw, Olaf van Tellingen, Anne Bolleboom, Zhaofei Yu, Yuanhong Tang, Clemens M.F. Dirven, Jort A. van Rij, Anna van der Stap
article en

Abstract

Seizures are frequent complications in brain tumor patients, yet the underlying neuronal mechanisms remain poorly defined. Here, we examined pathophysiological alterations in the peritumoral cortex of patients undergoing tumor resection. The synaptic activity, dendritic spine density, and gene expression of peritumoral pyramidal neurons differed significantly between patients with and without seizures. Using an inducible glioma rodent model, we characterized the progression of these alterations and their predictive value for seizure initiation. Computational simulations revealed that human cortical neurons are highly susceptible to synaptic and dendritic perturbations, which induce paroxysmal depolarizing shifts (PDS) in affected networks. Longitudinal analyses post-surgery showed that PDS were detectable prior to seizure onset in a subset of patients and reliably predicted post-resection seizure occurrence. These findings elucidate key neuronal substrates of tumor-associated seizures and suggest PDS as a potential biomarker for seizure risk, offering a foundation for targeted diagnostic and therapeutic strategies.

Nature CommunicationsVol. 16(1)
Netherlands Institute for Neuroscience (NL), Royal Netherlands Academy of Arts and Sciences (NL), Peking University (CN), Erasmus MC (NL), The Netherlands Cancer Institute (NL), Beijing Academy of Artificial Intelligence (CN), Oncode Institute (NL), University of Birmingham (GB), Erasmus University Rotterdam (NL)
Nederlandse Organisatie voor Wetenschappelijk Onderzoek
Openalex Percentile: Top 59%
Neuroscience and Neuropharmacology Research
DOIOpen Access PDFOpenAlex
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