title: Gap Junctions as Common Cause of High-Frequency Oscillations and Epileptic Seizures in a Computational Cascade of Neuronal Mass and Compartmental Modeling.
abstract: High frequency oscillations (HFO) appear to be a promising marker for delineating the seizure onset zone (SOZ) in patients with localization related epilepsy. It remains, however, a purely observational phenomenon and no common mechanism has been proposed to relate HFOs and seizure generation. In this work we show that a cascade of two computational models, one on detailed compartmental scale and a second one on neural mass scale can explain both the autonomous generation of HFOs and the presence of epileptic seizures as emergent properties. To this end we introduce axonal-axonal gap junctions on a microscopic level and explore their impact on the higher level neural mass model (NMM). We show that the addition of gap junctions can generate HFOs and simultaneously shift the operational point of the NMM from a steady state network into bistable behavior that can autonomously generate epileptic seizures. The epileptic properties of the system, or the probability to generate epileptic type of activity, increases gradually with the increase of the density of axonal-axonal gap junctions. We further demonstrate that ad hoc HFO detectors used in previous studies are applicable to our simulated data.
authors.affiliation: Stichting Epilepsie Instellingen Nederland, Achterweg 5, 2103 SW, Heemstede, The Netherlands.|Faculty of Technical Medicine, University of Twente, Drienerlolaan 5, 7522 NB, Enschede, The Netherlands.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Helling
authors.affiliation: Stichting Epilepsie Instellingen Nederland, Achterweg 5, 2103 SW, Heemstede, The Netherlands.
authors.forename: Marc M J
authors.initials: MM
authors.lastname: Koppert
authors.affiliation: Stichting Epilepsie Instellingen Nederland, Achterweg 5, 2103 SW, Heemstede, The Netherlands.
authors.forename: Gerhard H
authors.initials: GH
authors.lastname: Visser
authors.affiliation: Stichting Epilepsie Instellingen Nederland, Achterweg 5, 2103 SW, Heemstede, The Netherlands.|Image Sciences Institute - University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
authors.forename: Stiliyan N
authors.initials: SN
authors.lastname: Kalitzin
mesh_terms: D058256:Brain Waves; D003198:Computer Simulation; D004827:Epilepsy / Q000473:pathology*; D017629:Gap Junctions / Q000378:metabolism*; D008959:Models, Neurological; D009415:Nerve Net
keywords: High frequency oscillations; cascade modeling; epilepsy; gap junctions; neuronal mass model; seizures