A Reproducible Cortical Model of Focal Epileptiform Activity with a Multi-Biomarker Analysis Pipeline
- 1Instituto de Investigaciones Biomedicas de Barcelona, CSIC
Abstract
The development of surface-based therapeutic strategies, including extracranial illumination and epicortical electrical or optoelectronic neuromodulation, requires experimental models in which focal pathological activity can be generated and monitored within an accessible cortical region. Here, we established an acute cortical model of focal epileptiform activity in anesthetized mice based on local microinjection of 4-aminopyridine (4-AP) into the barrel cortex. This preparation provides precise spatial and temporal control of the epileptiform focus while enabling simultaneous electrophysiological sampling across cortical depth. To objectively characterize the induced activity, we implemented a Python-based analysis pipeline integrating complementary electrophysiological biomarkers, including oscillatory power, multi-unit activity, pathological fast ripples (250-650 Hz), and epileptiform bursts. Local 4-AP administration produced robust increases in gamma (30-100 Hz) power, multi-unit firing (MUA), fast ripple and burst activity. Pharmacological sensitivity of the framework was evaluated using carbamazepine, which robustly attenuated 4-AP-induced increases in all biomarkers. Together, this study provides a reproducible experimental and analytical framework for investigating focal cortical epileptiform activity and for the future evaluation of pharmacological, optical, and electrical interventions targeting superficial cortical networks.
Related
- A Reproducible MRI‐Based Pipeline for Longitudinal Tracking of Laser‐Assisted Bioprinted Cells in Three‐Dimensional Constructs
- EXCON: a scalable, reproducible Nextflow pipeline for CAFE-based gene EXpansion and CONtraction analysis
- BCell-Epitope-Prediction: A local, reproducible pipeline for multi-epitope vaccine design: integration and structural validation against a panel of PDB antigen-antibody complexes
- PIGSTI: a modular, reproducible pipeline for detecting species identity, pathogens, and microbes from animal palaeogenomic data
- multiomeR: a pipeline for reproducible analysis of large-scale single-nucleus Epi Multiome datasets
BibTeX
@misc{lopezcabezon2026reproducible,
title = {{A Reproducible Cortical Model of Focal Epileptiform Activity with a Multi-Biomarker Analysis Pipeline}},
author = {C. Lopez-Cabezon and T. A. Gener and A. Polo-Rodriguez and M. V. Puig},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.06.756259},
url = {https://www.biorxiv.org/content/10.64898/2026.10.06.756259v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - A Reproducible Cortical Model of Focal Epileptiform Activity with a Multi-Biomarker Analysis Pipeline
AU - C. Lopez-Cabezon
AU - T. A. Gener
AU - A. Polo-Rodriguez
AU - M. V. Puig
PY - 2026
DA - 2026/10/06
PB - bioRxiv
DO - 10.64898/2026.10.06.756259
UR - https://www.biorxiv.org/content/10.64898/2026.10.06.756259v1
AB - The development of surface-based therapeutic strategies, including extracranial illumination and epicortical electrical or optoelectronic neuromodulation, requires experimental models in which focal pathological activity can be generated and monitored within an accessible cortical region. Here, we established an acute cortical model of focal epileptiform activity in anesthetized mice based on local microinjection of 4-aminopyridine (4-AP) into the barrel cortex. This preparation provides precise spatial and temporal control of the epileptiform focus while enabling simultaneous electrophysiological sampling across cortical depth. To objectively characterize the induced activity, we implemented a Python-based analysis pipeline integrating complementary electrophysiological biomarkers, including oscillatory power, multi-unit activity, pathological fast ripples (250-650 Hz), and epileptiform bursts. Local 4-AP administration produced robust increases in gamma (30-100 Hz) power, multi-unit firing (MUA), fast ripple and burst activity. Pharmacological sensitivity of the framework was evaluated using carbamazepine, which robustly attenuated 4-AP-induced increases in all biomarkers. Together, this study provides a reproducible experimental and analytical framework for investigating focal cortical epileptiform activity and for the future evaluation of pharmacological, optical, and electrical interventions targeting superficial cortical networks.
ER -