{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T11:29:22Z","timestamp":1778066962221,"version":"3.51.4"},"reference-count":36,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2023,8,4]],"date-time":"2023-08-04T00:00:00Z","timestamp":1691107200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Visual assessment of magnetic resonance imaging (MRI) from the Human Epilepsy Project 1 (HEP1) found 18% of participants had atrophic brain changes relative to age without known etiology. Here, we identify the underlying factors related to brain volume differences in people with focal epilepsy enrolled in HEP1.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Enrollment data for participants with complete records and brain MRIs were analyzed, including 391 participants aged 12\u201360\u2009years. HEP1 excluded developmental or cognitive delay with intelligence quotient &lt;70, and participants reported any formal learning disability diagnoses, repeated grades, and remediation. Prediagnostic seizures were quantified by semiology, frequency, and duration. T1\u2010weighted brain MRIs were analyzed using Sequence Adaptive Multimodal Segmentation (FreeSurfer v7.2), from which a brain tissue volume to intracranial volume ratio was derived and compared to clinically relevant participant characteristics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Brain tissue volume changes observable on visual analyses were quantified, and a brain tissue volume to intracranial volume ratio was derived to compare with clinically relevant variables. Learning difficulties were associated with decreased brain tissue volume to intracranial volume, with a ratio reduction of .005 for each learning difficulty reported (95% confidence interval [CI]\u2009=\u2009\u2212.007 to \u2212.002, <jats:italic>p<\/jats:italic>\u2009=\u2009.0003). Each 10\u2010year increase in age at MRI was associated with a ratio reduction of .006 (95% CI\u2009=\u2009\u2212.007 to \u2212.005, <jats:italic>p<\/jats:italic>\u2009&lt;\u2009.0001). For male participants, the ratio was .011 less than for female participants (95% CI\u2009=\u2009\u2212.014 to \u2212.007, <jats:italic>p<\/jats:italic>\u2009&lt;\u2009.0001). There were no effects from seizures, employment, education, seizure semiology, or temporal lobe electroencephalographic abnormalities.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>This study shows lower brain tissue volume to intracranial volume in people with newly treated focal epilepsy and learning difficulties, suggesting developmental factors are an important marker of brain pathology related to neuroanatomical changes in focal epilepsy. Like the general population, there were also independent associations between brain volume, age, and sex in the study population.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.17727","type":"journal-article","created":{"date-parts":[[2023,7,30]],"date-time":"2023-07-30T13:47:50Z","timestamp":1690724870000},"page":"2761-2770","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Later onset focal epilepsy with roots in childhood: Evidence from early learning difficulty and brain volumes in the Human Epilepsy Project"],"prefix":"10.1111","volume":"64","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0747-7210","authenticated-orcid":false,"given":"Jacob","family":"Pellinen","sequence":"first","affiliation":[{"name":"University of Colorado School of Medicine  Aurora Colorado USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0123-2167","authenticated-orcid":false,"given":"Heath","family":"Pardoe","sequence":"additional","affiliation":[{"name":"Florey Institute of Neuroscience and Mental Health  Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Sillau","sequence":"additional","affiliation":[{"name":"University of Colorado School of Medicine  Aurora Colorado USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0517-2533","authenticated-orcid":false,"given":"Sarah","family":"Barnard","sequence":"additional","affiliation":[{"name":"Monash University  Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2242-8027","authenticated-orcid":false,"given":"Jacqueline","family":"French","sequence":"additional","affiliation":[{"name":"New York University Comprehensive Epilepsy Center  New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Knowlton","sequence":"additional","affiliation":[{"name":"University of California, San Francisco  San Francisco California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Lowenstein","sequence":"additional","affiliation":[{"name":"University of California, San Francisco  San Francisco California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory D.","family":"Cascino","sequence":"additional","affiliation":[{"name":"Mayo Clinic  Rochester Minnesota USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simon","family":"Glynn","sequence":"additional","affiliation":[{"name":"University of Michigan  Ann Arbor Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Graeme","family":"Jackson","sequence":"additional","affiliation":[{"name":"Florey Institute of Neuroscience and Mental Health  Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jerzy","family":"Szaflarski","sequence":"additional","affiliation":[{"name":"University of Alabama at Birmingham  Birmingham Alabama USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chris","family":"Morrison","sequence":"additional","affiliation":[{"name":"New York University Comprehensive Epilepsy Center  New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7471-882X","authenticated-orcid":false,"given":"Kimford J.","family":"Meador","sequence":"additional","affiliation":[{"name":"Stanford University Neuroscience Health Center  Palo Alto California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruben","family":"Kuzniecky","sequence":"additional","affiliation":[{"name":"Northwell Health  New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"the Human Epilepsy Project Investigators","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,8,4]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.YEBEH.2013.11.010"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/EPI.12649\/SUPPINFO"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.YEBEH.2022.108960"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.16707"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.13127"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/acem.14114"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.EPLEPSYRES.2023.107084"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.EJPN.2022.08.001"},{"key":"e_1_2_10_10_1","first-page":"1451","volume-title":"Imaging for Adults with Seizures and Epilepsy. 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