title: Preventive and Abortive Strategies for Stimulation Based Control of Epilepsy: A Computational Model Study.
abstract: Epilepsy is a condition in which periods of ongoing normal EEG activity alternate with periods of oscillatory behavior characteristic of epileptic seizures. The dynamics of the transitions between the two states are still unclear. Computational models provide a powerful tool to explore the underlying mechanisms of such transitions, with the purpose of eventually finding therapeutic interventions for this debilitating condition. In this study, the possibility to postpone seizures elicited by a decrease of inhibition is investigated by using external stimulation in a realistic bistable neuronal model consisting of two interconnected neuronal populations representing pyramidal cells and interneurons. In the simulations, seizures are induced by slowly decreasing the conductivity of GABA[Formula: see text] synaptic channels over time. Since the model is bistable, the system will change state from the initial steady state (SS) to the limit cycle (LS) state because of internal noise, when the inhibition falls below a certain threshold. Several state-independent stimulations paradigms are simulated. Their effectiveness is analyzed for various stimulation frequencies and intensities in combination with periodic and random stimulation sequences. The distributions of the time to first seizure in the presence of stimulation are compared with the situation without stimulation. In addition, stimulation protocols targeted to specific subsystems are applied with the objective of counteracting the baseline shift due to decreased inhibition in the system. Furthermore, an analytical model is used to investigate the effects of random noise. The relation between the strength of random noise stimulation, the control parameter of the system and the transitions between steady state and limit cycle are investigated. The study shows that it is possible to postpone epileptic activity by targeted stimulation in a realistic neuronal model featuring bistability and that it is possible to stop seizures by random noise in an analytical model.
authors.affiliation: * Foundation Epilepsy Institutes Netherlands (SEIN), Achterweg 5, 2103 SW Heemstede, The Netherlands.
authors.forename: Marc
authors.initials: M
authors.lastname: Koppert
authors.affiliation: * Foundation Epilepsy Institutes Netherlands (SEIN), Achterweg 5, 2103 SW Heemstede, The Netherlands.|† Image Sciences Institute, University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands.
authors.forename: Stiliyan
authors.initials: S
authors.lastname: Kalitzin
authors.affiliation: * Foundation Epilepsy Institutes Netherlands (SEIN), Achterweg 5, 2103 SW Heemstede, The Netherlands.|‡ Department of Neurosurgery, Free University Medical Center Amsterdam, 1007 MB Amsterdam, The Netherlands.
authors.forename: Demetrios
authors.initials: D
authors.lastname: Velis
authors.affiliation: 4 Swammerdam Institute for Life Sciences, University of Amsterdam, 1098 SM Amsterdam, The Netherlands.|5 Department of Bioengineering, Instituto Superior Técnico, University of Lisbon, 1049-001, Lisboa, Portugal.
authors.forename: Fernando
authors.initials: F
authors.lastname: Lopes Da Silva
authors.affiliation: † Image Sciences Institute, University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands.
authors.forename: Max A
authors.initials: MA
authors.lastname: Viergever
mesh_terms: D000465:Algorithms; D001921:Brain / Q000503:physiopathology; D003198:Computer Simulation; D004599:Electric Stimulation Therapy / Q000379:methods*; D004827:Epilepsy / Q000503:physiopathology / Q000628:therapy*; D006801:Humans; D007395:Interneurons / Q000502:physiology; D008564:Membrane Potentials / Q000502:physiology; D008959:Models, Neurological; D009433:Neural Inhibition / Q000502:physiology; D017966:Pyramidal Cells / Q000502:physiology; D011963:Receptors, GABA-A / Q000378:metabolism; D012640:Seizures / Q000503:physiopathology / Q000628:therapy; D013569:Synapses / Q000502:physiology; D013997:Time Factors
chemical_list: D011963:Receptors, GABA-A
keywords: Epilepsy; computational models; dynamic systems; seizure control