Early Increases in Hippocampal Synchrony Predict Chronic Epileptiform Burden in a Temporal Lobe Epilepsy Model
- 1Cleveland Clinic Research, Case Western Reserve University School of Medicine
Abstract
Temporal lobe epilepsy (TLE), the most common focal epilepsy, is often drug-resistant and arises predominantly in the hippocampus. Disease severity is conventionally assessed by seizure frequency and duration, yet epileptiform activity outside discrete seizures may also track disease progression. Whether this activity reflects hippocampal network reorganization as part of epileptogenesis, and whether such reorganization predicts chronic severity, is unknown. Here, we combined longitudinal two-photon calcium imaging of hippocampal CA1 neurons with repeated 24-hour EEG recordings that quantified epileptiform burden in the same pilocarpine treated mice over 16 weeks. CA1 firing and synchrony rose acutely, subsided during a latent period, and increased again chronically, with synchronized firing organized into brief waves that propagated in a consistent direction. Epileptiform burden followed a similar temporal trajectory and increasingly contained electrographic seizures. CA1 synchrony correlated with epileptiform burden and stratified mice into groups with distinct neuronal and electrographic outcomes. CA1 synchrony measured within three weeks of pilocarpine induction predicted chronic epileptiform burden, identifying early hippocampal synchrony as a candidate imaging biomarker and pointing to an early window for intervention in TLE.
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BibTeX
@misc{gasmi2026early,
title = {{Early Increases in Hippocampal Synchrony Predict Chronic Epileptiform Burden in a Temporal Lobe Epilepsy Model}},
author = {N. Gasmi and H. Tobin and D. Ahmadpour and G. Tahmasebi and A. Koohfar and S. Kalnitsky and M. Rogers-Carter and J. Icardi and S. Roehrs and S. Bhatia and H. Shindler and J. Manworren and P. Agochiya and S. Singh and S. Stanko and C. Richards and H. Suh and A. Alexopoulos and D. Serletis and I. Najm and H. Dana and D. Davalos},
howpublished = {bioRxiv},
year = {2026},
month = nov,
doi = {10.64898/2026.11.04.763700},
url = {https://www.biorxiv.org/content/10.64898/2026.11.04.763700v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Early Increases in Hippocampal Synchrony Predict Chronic Epileptiform Burden in a Temporal Lobe Epilepsy Model
AU - N. Gasmi
AU - H. Tobin
AU - D. Ahmadpour
AU - G. Tahmasebi
AU - A. Koohfar
AU - S. Kalnitsky
AU - M. Rogers-Carter
AU - J. Icardi
AU - S. Roehrs
AU - S. Bhatia
AU - H. Shindler
AU - J. Manworren
AU - P. Agochiya
AU - S. Singh
AU - S. Stanko
AU - C. Richards
AU - H. Suh
AU - A. Alexopoulos
AU - D. Serletis
AU - I. Najm
AU - H. Dana
AU - D. Davalos
PY - 2026
DA - 2026/11/04
PB - bioRxiv
DO - 10.64898/2026.11.04.763700
UR - https://www.biorxiv.org/content/10.64898/2026.11.04.763700v1
AB - Temporal lobe epilepsy (TLE), the most common focal epilepsy, is often drug-resistant and arises predominantly in the hippocampus. Disease severity is conventionally assessed by seizure frequency and duration, yet epileptiform activity outside discrete seizures may also track disease progression. Whether this activity reflects hippocampal network reorganization as part of epileptogenesis, and whether such reorganization predicts chronic severity, is unknown. Here, we combined longitudinal two-photon calcium imaging of hippocampal CA1 neurons with repeated 24-hour EEG recordings that quantified epileptiform burden in the same pilocarpine treated mice over 16 weeks. CA1 firing and synchrony rose acutely, subsided during a latent period, and increased again chronically, with synchronized firing organized into brief waves that propagated in a consistent direction. Epileptiform burden followed a similar temporal trajectory and increasingly contained electrographic seizures. CA1 synchrony correlated with epileptiform burden and stratified mice into groups with distinct neuronal and electrographic outcomes. CA1 synchrony measured within three weeks of pilocarpine induction predicted chronic epileptiform burden, identifying early hippocampal synchrony as a candidate imaging biomarker and pointing to an early window for intervention in TLE.
ER -