{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T08:21:35Z","timestamp":1763367695893,"version":"3.44.0"},"reference-count":35,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,4,7]],"date-time":"2025-04-07T00:00:00Z","timestamp":1743984000000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Objectives:<\/jats:title><jats:p>To investigate individual variations and outliers in cortical thickness among non\u2010alcoholic fatty liver disease (NAFLD) patients, ranging from hepatic steatosis to fibrosis, using neuroanatomical normative modeling.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods:<\/jats:title><jats:p>A cross\u2010sectional study with 2637 health check\u2010up subjects was conducted. Among NAFLD patients, hepatic steatosis (<jats:italic>n<\/jats:italic>\u00a0=\u00a0556) and fibrosis (<jats:italic>n<\/jats:italic>\u00a0=\u00a057) were determined by hepatic steatosis index and fibrosis\u20104 score, respectively. Cortical thickness in 148 different brain regions was assessed using T1\u2010weighted MRI scans. A publicly available neuroanatomical normative model analyzed cortical thickness distributions with data from around 58,000 participants. The hierarchical Bayesian regression was used to estimate cortical thickness deviation for each region, taking age, sex, and sites into account. On the basis of a normal adaptation set, <jats:italic>Z<\/jats:italic>\u2010scores below \u22121.96 or above +1.96 per region were classified as outliers. The total outlier count (tOC) was then calculated to quantify regional heterogeneity. Mass univariate analysis was conducted to compare steatosis and fibrosis groups, and the spatial patterns of regional heterogeneity were qualitatively analyzed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results:<\/jats:title><jats:p>Patients with hepatic fibrosis had a higher number of positive outlier regions (mean 6.3\u00a0\u00b1\u00a010.3) than hepatic steatosis (mean 4.2\u00a0\u00b1\u00a06.2, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.02). Mass univariate group difference testing of 148 brain regions revealed patients with hepatic fibrosis had 6 cortical areas thicker than hepatic steatosis. Two groups showed shared regional heterogeneity in the temporal cortex.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion:<\/jats:title><jats:p>Distinct brain atrophy patterns were observed in NAFLD patients compared to the normal group, with more frequent temporal cortex outliers in both hepatic steatosis and fibrosis. Hepatic fibrosis showed slightly increased cortical thickness relative to steatosis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/brb3.70466","type":"journal-article","created":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T03:24:32Z","timestamp":1744082672000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Normative Modeling Reveals Age\u2010Atypical Cortical Thickness Differences Between Hepatic Steatosis and Fibrosis in Non\u2010Alcoholic Fatty Liver Disease"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4614-1146","authenticated-orcid":false,"given":"Minchul","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Radiology, Samsung Kangbuk Hospital Sungkyunkwan University School of Medicine  Seoul South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Inpyeong","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Radiology Seoul National University Hospital and Seoul National University College of Medicine Seoul South Korea"},{"name":"Artificial Intelligence Collaborative Network Department of Radiology Seoul National University Hospital  Seoul South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyu Sung","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Radiology Seoul National University Hospital and Seoul National University College of Medicine Seoul South Korea"},{"name":"Artificial Intelligence Collaborative Network Department of Radiology Seoul National University Hospital  Seoul South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junhyeok","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Radiology, Interdisciplinary Program in Cancer Biology Seoul National University College of Medicine  Seoul South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minjung","family":"Ryu","sequence":"additional","affiliation":[{"name":"Department of Radiology Seoul National University Hospital and Seoul National University College of Medicine Seoul South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jung Hyun","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Radiology Seoul Metropolitan Government Seoul National University Boramae Medical Center  Seoul South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joon Ho","family":"Moon","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Seoul National University Bundang Hospital  Seongnam South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,4,7]]},"reference":[{"doi-asserted-by":"publisher","key":"e_1_2_13_2_1","DOI":"10.1055\/s-0040-1701443"},{"doi-asserted-by":"publisher","key":"e_1_2_13_3_1","DOI":"10.1002\/hep.23521"},{"doi-asserted-by":"publisher","key":"e_1_2_13_4_1","DOI":"10.1016\/j.jns.2021.120117"},{"doi-asserted-by":"publisher","key":"e_1_2_13_5_1","DOI":"10.1111\/j.2517-6161.1995.tb02031.x"},{"doi-asserted-by":"publisher","key":"e_1_2_13_6_1","DOI":"10.1038\/s42003-020-01212-9"},{"doi-asserted-by":"publisher","key":"e_1_2_13_7_1","DOI":"10.3389\/fneur.2021.606094"},{"doi-asserted-by":"publisher","key":"e_1_2_13_8_1","DOI":"10.1038\/s41598-020-59433-1"},{"volume-title":"How Not to Be Wrong: The Hidden Maths of Everyday Life","year":"2014","author":"Ellenberg J.","key":"e_1_2_13_9_1"},{"doi-asserted-by":"publisher","key":"e_1_2_13_10_1","DOI":"10.1016\/j.neuroimage.2021.118715"},{"doi-asserted-by":"publisher","key":"e_1_2_13_11_1","DOI":"10.1016\/j.neuroimage.2020.117012"},{"doi-asserted-by":"publisher","key":"e_1_2_13_12_1","DOI":"10.3389\/fmed.2020.00448"},{"doi-asserted-by":"publisher","key":"e_1_2_13_13_1","DOI":"10.4093\/dmj.2020.0115"},{"doi-asserted-by":"publisher","key":"e_1_2_13_14_1","DOI":"10.1016\/j.ebiom.2023.104679"},{"doi-asserted-by":"publisher","key":"e_1_2_13_15_1","DOI":"10.3748\/wjg.v22.i45.9880"},{"doi-asserted-by":"publisher","key":"e_1_2_13_16_1","DOI":"10.1371\/journal.pone.0278776"},{"doi-asserted-by":"publisher","key":"e_1_2_13_17_1","DOI":"10.3390\/jcm10040673"},{"doi-asserted-by":"publisher","key":"e_1_2_13_18_1","DOI":"10.1002\/hep.510260405"},{"doi-asserted-by":"publisher","key":"e_1_2_13_19_1","DOI":"10.1016\/j.dld.2009.08.002"},{"doi-asserted-by":"publisher","key":"e_1_2_13_20_1","DOI":"10.3389\/fnins.2023.1305624"},{"doi-asserted-by":"publisher","key":"e_1_2_13_21_1","DOI":"10.1161\/STROKEAHA.117.020495"},{"doi-asserted-by":"publisher","key":"e_1_2_13_22_1","DOI":"10.1038\/ajg.2016.453"},{"doi-asserted-by":"publisher","key":"e_1_2_13_23_1","DOI":"10.1002\/alz.12795"},{"doi-asserted-by":"publisher","key":"e_1_2_13_24_1","DOI":"10.5607\/en21036"},{"doi-asserted-by":"publisher","key":"e_1_2_13_25_1","DOI":"10.3389\/fphar.2020.603926"},{"doi-asserted-by":"publisher","key":"e_1_2_13_26_1","DOI":"10.1038\/s41598-021-95098-0"},{"doi-asserted-by":"publisher","key":"e_1_2_13_27_1","DOI":"10.1016\/j.neuroimage.2017.12.059"},{"doi-asserted-by":"publisher","key":"e_1_2_13_28_1","DOI":"10.7554\/eLife.85082"},{"doi-asserted-by":"publisher","key":"e_1_2_13_29_1","DOI":"10.7554\/eLife.72904"},{"doi-asserted-by":"publisher","key":"e_1_2_13_30_1","DOI":"10.1038\/s41596-022-00696-5"},{"doi-asserted-by":"publisher","key":"e_1_2_13_31_1","DOI":"10.1002\/hep.21178"},{"doi-asserted-by":"publisher","key":"e_1_2_13_32_1","DOI":"10.1186\/s12944-024-02031-1"},{"doi-asserted-by":"publisher","key":"e_1_2_13_33_1","DOI":"10.1212\/WNL.0000000000207298"},{"doi-asserted-by":"publisher","key":"e_1_2_13_34_1","DOI":"10.1111\/ene.16048"},{"doi-asserted-by":"publisher","key":"e_1_2_13_35_1","DOI":"10.1001\/jamaneurol.2017.3229"},{"doi-asserted-by":"publisher","key":"e_1_2_13_36_1","DOI":"10.1002\/hep.28431"}],"container-title":["Brain and Behavior"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/brb3.70466","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T08:43:20Z","timestamp":1759135400000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/brb3.70466"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4]]},"references-count":35,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,4]]}},"alternative-id":["10.1002\/brb3.70466"],"URL":"https:\/\/doi.org\/10.1002\/brb3.70466","archive":["Portico"],"relation":{},"ISSN":["2162-3279","2162-3279"],"issn-type":[{"type":"print","value":"2162-3279"},{"type":"electronic","value":"2162-3279"}],"subject":[],"published":{"date-parts":[[2025,4]]},"assertion":[{"value":"2024-12-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70466"}}