{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,23]],"date-time":"2025-08-23T00:06:44Z","timestamp":1755907604047,"version":"3.44.0"},"reference-count":32,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T00:00:00Z","timestamp":1744156800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["HHS 75N95022C00007"],"award-info":[{"award-number":["HHS 75N95022C00007"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Variability in the frequency, timing, and pattern of seizures may influence the assessment of the effect of antiseizure medications (ASMs) when measuring seizure frequency, especially in patients with infrequent seizures. A low seizure rate is an exclusion criterion for enrollment of patients with epilepsy in clinical trials and requires prolonged periods of seizure monitoring, thus delaying appropriate treatment interventions. We investigated whether an electroencephalogram (EEG)\u2013based complexity measure of seizure susceptibility of epileptic mice provides a reliable alternative to seizure frequency for evaluating the efficacy of ASMs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used a mouse model of acquired epilepsy characterized by variability in seizure frequency over time and among mice, as observed in humans. We analyzed EEG recordings from chronic epileptic mice (<jats:italic>n<\/jats:italic>\u2009=\u2009106) at baseline and during treatment with phenobarbital, valproate, carbamazepine, or phenytoin. We used recurrence quantification analysis to detect increased autocorrelation and critical slowing\u2010down, two signatures of criticality that together contribute to estimate the dimension of phase\u2013space of the EEG signals. The measurements of dimension and seizure frequency were compared as proxies for seizure susceptibility by correlation tests and evaluation of ASM efficacy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Dimension provided a statistically robust (inverse) estimate of seizure susceptibility of mice, including mice with low seizure frequency or no seizures during the observation periods. In contrast, seizure frequency provided a reliable measure only in mice with a high seizure rate. Consistently, evaluation of ASM efficacy using dimension variations accurately reproduced seizure responsiveness patterns in this mouse model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>EEG\u2010based dimension provides a reliable measure of mouse propensity to experience seizures as well as ASM efficacy, regardless of seizure rates. Measuring dimension variation should facilitate the inclusion of subjects with low seizure rate in preclinical and clinical trials while also shortening the periods of monitoring. This could accelerate both the development of new treatments and therapeutic decisions in the medical field.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.18397","type":"journal-article","created":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T11:52:51Z","timestamp":1744199571000},"page":"3035-3047","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>EEG<\/scp> signal dimension is an index of seizure propensity and antiseizure medication effects in a mouse model of acquired epilepsy"],"prefix":"10.1111","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5477-2263","authenticated-orcid":false,"given":"Massimo","family":"Rizzi","sequence":"first","affiliation":[{"name":"Department of Acute Brain and Cardiovascular Injury Istituto di Ricerche Farmacologiche Mario Negri IRCCS  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5774-5180","authenticated-orcid":false,"given":"Peter J.","family":"West","sequence":"additional","affiliation":[{"name":"Anticonvulsant Drug Development Program, Department of Pharmacology &amp; Toxicology University of Utah  Salt Lake City Utah USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0573-6175","authenticated-orcid":false,"given":"Annamaria","family":"Vezzani","sequence":"additional","affiliation":[{"name":"Department of Acute Brain and Cardiovascular Injury Istituto di Ricerche Farmacologiche Mario Negri IRCCS  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2660-8826","authenticated-orcid":false,"given":"Karen S.","family":"Wilcox","sequence":"additional","affiliation":[{"name":"Anticonvulsant Drug Development Program, Department of Pharmacology &amp; Toxicology University of Utah  Salt Lake City Utah USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4640-804X","authenticated-orcid":false,"given":"Alessandro","family":"Giuliani","sequence":"additional","affiliation":[{"name":"Environment and Health Department Istituto Superiore di Sanit\u00e1  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,4,9]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2019.02.006"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010017\u201002577\u2010y"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2005.08.018"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2021.113954"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2016.12.007"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.16406"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17568"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.14503"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2021.02.001"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2357"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature08227"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2023.110684"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010020\u201015908\u20103"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2023.106251"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2018.12.014"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/0013\u20104694(95)00071\u20106"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinph.2008.04.005"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.physrep.2006.11.001"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1994.76.2.965"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0013\u20109580.2003.12005.x"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1225244"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.physleta.2016.02.024"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0375-9601(00)00815-X"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2019.05.036"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528\u20101157.1998.tb01268.x"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awz130"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2016.05.012"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2015.02.029"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0013\u20104694(97)00027\u20101"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2018.24"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnetp.2023.1338864"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/epi4.12588"}],"container-title":["Epilepsia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/epi.18397","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T10:07:59Z","timestamp":1755857279000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/epi.18397"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,9]]},"references-count":32,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2025,8]]}},"alternative-id":["10.1111\/epi.18397"],"URL":"https:\/\/doi.org\/10.1111\/epi.18397","archive":["Portico"],"relation":{},"ISSN":["0013-9580","1528-1167"],"issn-type":[{"type":"print","value":"0013-9580"},{"type":"electronic","value":"1528-1167"}],"subject":[],"published":{"date-parts":[[2025,4,9]]},"assertion":[{"value":"2024-10-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication 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