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Focal seizures are organized by feedback between neural activity and ion concentration changes

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cris.lastimport.scopus2024-02-12T20:29:17Z
dc.abstract.enHuman and animal EEG data demonstrate that focal seizures start with low-voltage fast activity, evolve into rhythmic burst discharges and are followed by a period of suppressed background activity. This suggests that processes with dynamics in the range of tens of seconds govern focal seizure evolution. We investigate the processes associated with seizure dynamics by complementing the Hodgkin-Huxley mathematical model with the physical laws that dictate ion movement and maintain ionic gradients. Our biophysically realistic computational model closely replicates the electrographic pattern of a typical human focal seizure characterized by low voltage fast activity onset, tonic phase, clonic phase and postictal suppression. Our study demonstrates, for the first time in silico, the potential mechanism of seizure initiation by inhibitory interneurons via the initial build-up of extracellular K+ due to intense interneuronal spiking. The model also identifies ionic mechanisms that may underlie a key feature in seizure dynamics, that is, progressive slowing down of ictal discharges towards the end of seizure. Our model prediction of specific scaling of inter-burst intervals is confirmed by seizure data recorded in the whole guinea pig brain in vitro and in humans, suggesting that the observed termination pattern may hold across different species. Our results emphasize ionic dynamics as elementary processes behind seizure generation and indicate targets for new therapeutic strategies.
dc.affiliationUniwersytet Warszawski
dc.contributor.authorSuffczyński, Piotr
dc.contributor.authorGnatkovsky, Vadym
dc.contributor.authorCurtis, Marco de
dc.contributor.authorGentiletti, Damiano
dc.date.accessioned2024-01-25T01:14:03Z
dc.date.available2024-01-25T01:14:03Z
dc.date.issued2022
dc.description.financeŚrodki finansowe, o których mowa w art. 365 pkt. 2 ustawy
dc.description.volume11
dc.identifier.doi10.7554/ELIFE.68541
dc.identifier.issn2050-084X
dc.identifier.urihttps://repozytorium.uw.edu.pl//handle/item/107312
dc.identifier.weblinkhttps://cdn.elifesciences.org/articles/68541/elife-68541-v2.pdf
dc.languageeng
dc.pbn.affiliationphysical sciences
dc.relation.ispartofeLife
dc.rightsClosedAccess
dc.sciencecloudnosend
dc.titleFocal seizures are organized by feedback between neural activity and ion concentration changes
dc.typeJournalArticle
dspace.entity.typePublication