{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:20:01Z","timestamp":1792790401299,"version":"4.5.0"},"posted":{"date-parts":[[2026,9,23]]},"group-title":"Neuroscience","reference-count":68,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"NINDS","award":["R01NS115868"],"award-info":[{"award-number":["R01NS115868"]}],"id":[{"id":"https:\/\/ror.org\/01s5ya894","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Childhood absence epilepsy (CAE), the most common childhood epilepsy syndrome, is associated with bursts of generalized thalamocortical spike-wave discharges and cognitive impairment, yet the physiological mechanisms linking disease activity, treatment, and cognition remain unclear. Sleep spindles, generated by thalamocortical circuits, are associated with cognitive function and may be disrupted by epileptic activity. Here, we retrospectively studied 87 EEGs from 53 children with active and resolved CAE and 87 age- and sex-matched controls to evaluate sleep spindle activity across disease states and its association with antiseizure medication (ASM) exposure. We found that children with active CAE had reduced spindle rates across all cortical regions compared to those with resolved CAE and controls, with the largest reduction in the frontal region, where epileptic spike activity was also most prominent. Spindle rate was inversely correlated with epileptic spike rate, consistent with a shared thalamocortical circuitry. The association between ASM exposure and spindle rate varied by disease state. In active CAE, treated children had higher spindle rates than untreated children. In resolved CAE, treated children had lower spindle rates than untreated children. In contrast, ASM-related differences in spike rate were more limited, although a medication-specific reduction was observed in active CAE. These findings support sleep spindle rate as a candidate physiological marker of disease state and ASM exposure in children with CAE. Given the established role of sleep spindles in memory consolidation, these findings support testing of whether spindle disruption provides a mechanistic link between epileptic thalamocortical activity and cognitive vulnerability in CAE.<\/jats:p>\n                <jats:sec>\n                  <jats:title>Significance Statement<\/jats:title>\n                  <jats:p>Childhood absence epilepsy (CAE) is a common childhood generalized epilepsy characterized by abnormal thalamocortical activity and cognitive difficulties. Here, we show that sleep spindle activity is globally reduced during active CAE, particularly in frontal regions, and normalizes after disease resolution. Spindle activity was anticorrelated with epileptic spike rate and impacted by antiseizure medication exposure. These results support the hypothesis that epileptic spikes and sleep spindles share thalamocortical circuitry and promote sleep spindles as a candidate physiological biomarker to link epileptic activity with cognitive vulnerability in CAE.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.09.17.752393","type":"posted-content","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T21:15:16Z","timestamp":1790198116000},"source":"Crossref","is-referenced-by-count":0,"title":["Sleep spindle deficits in childhood absence epilepsy improve with antiseizure treatment and disease resolution"],"prefix":"10.64898","author":[{"given":"Skyler K.","family":"Goodman","sequence":"first","affiliation":[{"name":"Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Yi","sequence":"additional","affiliation":[{"name":"Department of Neurology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dhinakaran M.","family":"Chinappen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Kennedy Krieger Institute, Baltimore, Maryland, USA"},{"name":"Department of Neurology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A.","family":"Kramer","sequence":"additional","affiliation":[{"name":"Department of Applied Mathematics and Statistics, Johns Hopkins University, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine J.","family":"Chu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Kennedy Krieger Institute, Baltimore, Maryland, USA"},{"name":"Department of Neurology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4189-2546","authenticated-orcid":false,"given":"Hunki","family":"Kwon","sequence":"additional","affiliation":[{"name":"Department of Neurology, Kennedy Krieger Institute, Baltimore, Maryland, USA"},{"name":"Department of Neurology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026092614301135000_2026.09.17.752393v1.1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17241"},{"key":"2026092614301135000_2026.09.17.752393v1.2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.1995.tb01060.x"},{"key":"2026092614301135000_2026.09.17.752393v1.3","doi-asserted-by":"crossref","first-page":"1796","DOI":"10.1111\/j.1528-1167.2005.00277.x","article-title":"Childhood absence epilepsy: evolution and prognostic factors","volume":"46","year":"2005","journal-title":"Epilepsia"},{"key":"2026092614301135000_2026.09.17.752393v1.4","doi-asserted-by":"publisher","DOI":"10.1684\/epd.2020.1192"},{"key":"2026092614301135000_2026.09.17.752393v1.5","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17236"},{"key":"2026092614301135000_2026.09.17.752393v1.6","doi-asserted-by":"publisher","DOI":"10.1038\/nrn811"},{"key":"2026092614301135000_2026.09.17.752393v1.7","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1212\/01.wnl.0000228257.60184.82","article-title":"Electroclinical features of absence seizures in childhood absence epilepsy","volume":"67","year":"2006","journal-title":"Neurology"},{"key":"2026092614301135000_2026.09.17.752393v1.8","doi-asserted-by":"publisher","DOI":"10.1093\/BRAIN\/AWAA072"},{"key":"2026092614301135000_2026.09.17.752393v1.9","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2008.01680.x"},{"key":"2026092614301135000_2026.09.17.752393v1.10","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3182a9f3ca"},{"key":"2026092614301135000_2026.09.17.752393v1.11","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0902014"},{"key":"2026092614301135000_2026.09.17.752393v1.12","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.56.8.1047"},{"key":"2026092614301135000_2026.09.17.752393v1.13","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2012.03706.x"},{"key":"2026092614301135000_2026.09.17.752393v1.14","doi-asserted-by":"publisher","DOI":"10.1007\/s11065-019-09419-2"},{"key":"2026092614301135000_2026.09.17.752393v1.15","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000004514"},{"key":"2026092614301135000_2026.09.17.752393v1.16","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-023-01381-w"},{"key":"2026092614301135000_2026.09.17.752393v1.17","doi-asserted-by":"crossref","unstructured":"Kwon H , Walsh KG , Berja ED , et al. 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