{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T21:55:17Z","timestamp":1772142917266,"version":"3.50.1"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,3,20]],"date-time":"2023-03-20T00:00:00Z","timestamp":1679270400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Dravet syndrome (Dravet) is a rare and severe form of developmental epileptic encephalopathy. Antiseizure medications (ASMs) for Dravet patients include valproic acid (VA) or clobazam (CLB), with or without stiripentol (STP), while sodium channel blockers like carbamazepine (CBZ) or lamotrigine (LTG) are contraindicated. In addition to their effect on epileptic phenotypes, ASMs were shown to modify the properties of background neuronal activity. Nevertheless, little is known about these background properties alterations in Dravet. Here, utilizing Dravet mice (DS, <jats:italic>Scn1a<\/jats:italic><jats:sup>A1783V\/WT<\/jats:sup>), we tested the acute effect of several ASMs on background electrocorticography (ECoG) activity and frequency of interictal spikes. Compared to wild-type mice, background ECoG activity in DS mice had lower power and reduced phase coherence, which was not corrected by any of the tested ASMs. However, acute administration of Dravet-recommended drugs, VA, CLB, or a combination of CLB + STP, caused, in most mice, a reduction in the frequency of interictal spikes, alongside an increase in the relative contribution of the beta frequency band. Conversely, CBZ and LTG increased the frequency of interictal spikes, with no effect on background spectral properties. Moreover, we uncovered a correlation between the reduction in interictal spike frequency, the drug-induced effect on the power of background activity, and a spectral shift toward higher frequency bands. Together, these data provide a comprehensive analysis of the effect of selected ASMs on the properties of background neuronal oscillations, and highlight a possible correlation between their effect on epilepsy and background activity.<\/jats:p>","DOI":"10.3389\/fphar.2023.1118216","type":"journal-article","created":{"date-parts":[[2023,3,20]],"date-time":"2023-03-20T04:24:21Z","timestamp":1679286261000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Acute effect of antiseizure drugs on background oscillations in Scn1aA1783V Dravet syndrome mouse model"],"prefix":"10.3389","volume":"14","author":[{"given":"Shir","family":"Quinn","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina","family":"Brusel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mor","family":"Ovadia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Moran","family":"Rubinstein","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,3,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"105209","DOI":"10.1016\/j.nbd.2020.105209","article-title":"Developmental alterations in firing properties of hippocampal CA1 inhibitory and excitatory neurons in a mouse model of Dravet syndrome","volume":"148","author":"Almog","year":"2021","journal-title":"Neurobiol. Dis."},{"key":"B2","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1023\/A:1014814924965","article-title":"Mechanisms of action of carbamazepine and its derivatives, oxcarbazepine, BIA 2-093, and BIA 2-024","volume":"27","author":"Ambr\u00f3sio","year":"2002","journal-title":"Neurochem. Res."},{"key":"B3","doi-asserted-by":"publisher","first-page":"106996","DOI":"10.1016\/J.EPLEPSYRES.2022.106996","article-title":"Quantitative electroencephalographic analysis as a potential biomarker of response to treatment with cannabidiol","volume":"185","author":"Armstrong","year":"2022","journal-title":"Epilepsy Res."},{"key":"B4","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1111\/J.1535-7511.2006.00146.X","article-title":"Do interictal spikes sustain seizures and epileptogenesis?","volume":"6","author":"Avoli","year":"2006","journal-title":"Epilepsy Curr."},{"key":"B5","doi-asserted-by":"publisher","first-page":"e0224642","DOI":"10.1371\/JOURNAL.PONE.0224642","article-title":"Robust, automated sleep scoring by a compact neural network with distributional shift correction","volume":"14","author":"Barger","year":"2019","journal-title":"PLoS One"},{"key":"B6","doi-asserted-by":"publisher","first-page":"175","DOI":"10.3389\/fnsys.2015.00175","article-title":"A tutorial review of functional connectivity analysis methods and their interpretational pitfalls","volume":"9","author":"Bastos","year":"2016","journal-title":"Front. Syst. Neurosci."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s40810-015-0015-7","article-title":"Coherence a measure of the brain networks: Past and present","volume":"2","author":"Bowyer","year":"2016","journal-title":"Neuropsychiatr. Electrophysiol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1463","DOI":"10.1016\/J.CLINPH.2020.03.029","article-title":"Resting state EEG power research in attention-deficit\/hyperactivity disorder: A review update","volume":"131","author":"Clarke","year":"2020","journal-title":"Clin. Neurophysiol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1016\/J.EPLEPSYRES.2006.05.003","article-title":"Quantitative EEG effects of carbamazepine, oxcarbazepine, valproate, lamotrigine, and possible clinical relevance of the findings","volume":"70","author":"Clemens","year":"2006","journal-title":"Epilepsy Res."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1154","DOI":"10.1111\/epi.14191","article-title":"Influence of contraindicated medication use on cognitive outcome in Dravet syndrome and age at first afebrile seizure as a clinical predictor in SCN1A-related seizure phenotypes","volume":"59","author":"de Lange","year":"2018","journal-title":"Epilepsia"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1778","DOI":"10.1093\/cercor\/bhw002","article-title":"Unaltered network activity and interneuronal firing during spontaneous cortical dynamics in vivo in a mouse model of Severe Myoclonic Epilepsy of Infancy","volume":"26","author":"De Stasi","year":"2016","journal-title":"Cereb. Cortex"},{"key":"B12","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1111\/j.1528-1167.2011.02994.x","article-title":"The core Dravet syndrome phenotype","volume":"52","author":"Dravet","year":"2011","journal-title":"Epilepsia"},{"key":"B13","doi-asserted-by":"publisher","first-page":"2289","DOI":"10.1111\/epi.16662","article-title":"Convulsive seizures and some behavioral comorbidities are uncoupled in the Scn1aA1783V Dravet syndrome mouse model","volume":"61","author":"Fadila","year":"2020","journal-title":"Epilepsia"},{"key":"B14","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1111\/J.1528-1167.2011.03008.X","article-title":"The effects of stiripentol on GABAA receptors","volume":"52","author":"Fisher","year":"2011","journal-title":"Epilepsia"},{"key":"B15","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.seizure.2016.10.014","article-title":"From genotype to phenotype in Dravet disease","volume":"44","author":"Gataullina","year":"2017","journal-title":"Seizure"},{"key":"B16","doi-asserted-by":"publisher","first-page":"114090","DOI":"10.1016\/J.EXPNEUROL.2022.114090","article-title":"Life-span characterization of epilepsy and comorbidities in Dravet syndrome mice carrying a targeted deletion of exon 1 of the Scn1a gene","volume":"354","author":"Gerbatin","year":"2022","journal-title":"Exp. Neurol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1007\/BF00426786","article-title":"Neuropharmacological profile of clobazam, a new 1\u2032, 5\u2032-benzodiazepine","volume":"58","author":"Gerhards","year":"1978","journal-title":"Psychopharmacol. Berl."},{"key":"B18","doi-asserted-by":"publisher","first-page":"e0120239","DOI":"10.1371\/journal.pone.0120239","article-title":"Functional characterization of the 1,5-benzodiazepine clobazam and its major active metabolite n-desmethylclobazam at human GABAA receptors expressed in xenopus laevis oocytes","volume":"10","author":"Hammer","year":"2015","journal-title":"PLoS One"},{"key":"B19","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1111\/j.1440-1681.1988.tb01015.x","article-title":"Relationship between the dose-response effects of diazepam and clobazam on electroencephalographic parameters and on kindled amygdaloid seizure activity in rats","volume":"15","author":"Harris","year":"1988","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1002\/acn3.413","article-title":"Screening of conventional anticonvulsants in a genetic mouse model of epilepsy","volume":"4","author":"Hawkins","year":"2017","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1007\/s00335-021-09877-1","article-title":"Gabra2 is a genetic modifier of Dravet syndrome in mice","volume":"32","author":"Hawkins","year":"2021","journal-title":"Mamm. Genome"},{"key":"B22","doi-asserted-by":"publisher","first-page":"682767","DOI":"10.3389\/fphar.2021.682767","article-title":"Perampanel reduces hyperthermia-induced seizures in Dravet syndrome mouse model","volume":"12","author":"Ho","year":"2021","journal-title":"Front. Pharmacol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1016\/j.braindev.2011.08.009","article-title":"Maturation of EEG oscillations in children with sodium channel mutations","volume":"34","author":"Holmes","year":"2012","journal-title":"Brain Dev."},{"key":"B24","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1111\/EPI.12186","article-title":"EEG abnormalities as a biomarker for cognitive comorbidities in pharmacoresistant epilepsy","volume":"54","author":"Holmes","year":"2013","journal-title":"Epilepsia"},{"key":"B25","doi-asserted-by":"publisher","first-page":"2362","DOI":"10.1111\/J.1528-1167.2009.02179.X","article-title":"Stiripentol open study in Japanese patients with Dravet syndrome","volume":"50","author":"Inoue","year":"2009","journal-title":"Epilepsia"},{"key":"B26","doi-asserted-by":"publisher","first-page":"S25","DOI":"10.1111\/epi.14700","article-title":"SCN1A\/NaV1.1 channelopathies: Mechanisms in expression systems, animal models, and human iPSC models","volume":"60","author":"Mantegazza","year":"2019","journal-title":"Epilepsia"},{"key":"B27","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1111\/gbb.12099","article-title":"Mapping genetic modifiers of survival in a mouse model of Dravet syndrome","volume":"13","author":"Miller","year":"2014","journal-title":"Genes, Brain Behav."},{"key":"B28","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1016\/J.SEIZURE.2021.06.007","article-title":"Age-related evolution of EEG in Dravet syndrome: Meta-analysis of 155 patients","volume":"91","author":"Minato","year":"2021","journal-title":"Seizure"},{"key":"B29","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.nbd.2014.01.006","article-title":"Strain- and age-dependent hippocampal neuron sodium currents correlate with epilepsy severity in Dravet syndrome mice","volume":"65","author":"Mistry","year":"2014","journal-title":"Neurobiol. Dis."},{"key":"B30","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1186\/s12883-022-02577-6","article-title":"Comparative analysis of background EEG activity in juvenile myoclonic epilepsy during valproic acid treatment: A standardized, low-resolution, brain electromagnetic tomography (sLORETA) study","volume":"22","author":"Moon","year":"2022","journal-title":"BMC Neurol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"5903","DOI":"10.1523\/JNEUROSCI.5270-06.2007","article-title":"NaV1.1 localizes to axons of parvalbumin-positive inhibitory interneurons: A circuit basis for epileptic seizures in mice carrying an Scn1a gene mutation","volume":"27","author":"Ogiwara","year":"2007","journal-title":"J. Neurosci."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1665","DOI":"10.1111\/epi.16925","article-title":"Development of an antiseizure drug screening platform for Dravet syndrome at the NINDS contract site for the Epilepsy Therapy Screening Program","volume":"62","author":"Pernici","year":"2021","journal-title":"Epilepsia"},{"key":"B33","doi-asserted-by":"publisher","first-page":"242","DOI":"10.3389\/fphar.2015.00242","article-title":"Management of bipolar depression with lamotrigine: An antiepileptic mood stabilizer","volume":"6","author":"Prabhavalkar","year":"2015","journal-title":"Front. Pharmacol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"14172","DOI":"10.1038\/s41598-019-50627-w","article-title":"Epilepsy and neuropsychiatric comorbidities in mice carrying a recurrent Dravet syndrome SCN1A missense mutation","volume":"9","author":"Ricobaraza","year":"2019","journal-title":"Sci. Rep."},{"key":"B35","doi-asserted-by":"publisher","first-page":"2090","DOI":"10.1007\/s00018-007-7079-x","article-title":"The mechanisms of action of valproate in neuropsychiatric disorders: Can we see the forest for the trees?","volume":"64","author":"Rosenberg","year":"2007","journal-title":"Cell. Mol. Life Sci."},{"key":"B36","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1016\/j.nbd.2014.09.017","article-title":"Genetic background modulates impaired excitability of inhibitory neurons in a mouse model of Dravet syndrome","volume":"73","author":"Rubinstein","year":"2015","journal-title":"Neurobiol. Dis."},{"key":"B37","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1093\/BRAIN\/AWL304","article-title":"Assessing seizure dynamics by analysing the correlation structure of multichannel intracranial EEG","volume":"130","author":"Schindler","year":"2007","journal-title":"Brain"},{"key":"B38","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/J.BRAINDEV.2015.06.008","article-title":"Efficacy of antiepileptic drugs for the treatment of Dravet syndrome with different genotypes","volume":"38","author":"Shi","year":"2016","journal-title":"Brain Dev."},{"key":"B39","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1007\/S00421-010-1521-8","article-title":"Teager\u2013Kaiser energy operator signal conditioning improves EMG onset detection","volume":"110","author":"Solnik","year":"2010","journal-title":"Eur. J. Appl. Physiol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1007\/978-94-017-8914-1_3","article-title":"What is the importance of abnormal \u201cbackground\u201d activity in seizure generation?","volume":"813","author":"Staba","year":"2014","journal-title":"Adv. Exp. Med. Biol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1093\/cercor\/bhj127","article-title":"Small-world networks and functional connectivity in Alzheimer\u2019s disease","volume":"17","author":"Stam","year":"2007","journal-title":"Cereb. Cortex"},{"key":"B42","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1007\/s40263-022-00898-1","article-title":"A practical guide to the treatment of Dravet syndrome with anti-seizure medication","volume":"36","author":"Strzelczyk","year":"2022","journal-title":"CNS Drugs"},{"key":"B43","doi-asserted-by":"publisher","first-page":"2764","DOI":"10.1523\/JNEUROSCI.2370-19.2020","article-title":"Interneuron desynchronization precedes seizures in a mouse model of Dravet syndrome","volume":"40","author":"Tran","year":"2020","journal-title":"J. Neurosci."},{"key":"B44","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1038\/nature14979","article-title":"Control of REM sleep by ventral medulla GABAergic neurons","volume":"526","author":"Weber","year":"2015","journal-title":"Nature"},{"key":"B45","doi-asserted-by":"publisher","first-page":"1761","DOI":"10.1111\/EPI.17274","article-title":"International consensus on diagnosis and management of Dravet syndrome","volume":"63","author":"Wirrell","year":"2022","journal-title":"Epilepsia"},{"key":"B46","doi-asserted-by":"publisher","first-page":"1142","DOI":"10.1038\/nn1754","article-title":"Reduced sodium current in GABAergic interneurons in a mouse model of severe myoclonic epilepsy in infancy","volume":"9","author":"Yu","year":"2006","journal-title":"Nat. Neurosci."},{"key":"B47","doi-asserted-by":"publisher","first-page":"26549","DOI":"10.1073\/pnas.1909696116","article-title":"Valproic acid interactions with the NavMs voltage-gated sodium channel","volume":"116","author":"Zanatta","year":"2019","journal-title":"Proc. Natl. Acad. Sci."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2023.1118216\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,20]],"date-time":"2023-03-20T04:24:23Z","timestamp":1679286263000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2023.1118216\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,20]]},"references-count":47,"alternative-id":["10.3389\/fphar.2023.1118216"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2023.1118216","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,20]]},"article-number":"1118216"}}