{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T05:30:51Z","timestamp":1788067851506,"version":"build-2784847793"},"reference-count":60,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,3,20]],"date-time":"2025-03-20T00:00:00Z","timestamp":1742428800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      In temporal lobe epilepsy (TLE), detection of the epileptogenic zone predicts a good surgical outcome. When submitted to\n                      <jats:sup>18<\/jats:sup>\n                      F\u2010fluorodeoxyglucose positron emission tomography (PET), some patients display lateralized, focal hypometabolism in the temporal lobe (PET+), whereas others appear normometabolic (PET\u2212). However, the mechanism behind this metabolic difference remains unclear. This study aimed to identify differential molecular mechanisms in these patient subtypes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Neocortical and hippocampal biopsies of TLE patients (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20093 PET+,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20093 PET\u2212) and nonepileptic postmortem controls (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20093) were analyzed for lipid distribution using mass spectrometry imaging (MSI). Laser capture microdissection of the neocortical gray matter and hippocampal cornu ammonis and dentate gyrus was guided by MSI\u2010derived lipid profiles and histological annotations. Dissected areas were then subjected to liquid chromatography\u2013 tandem mass spectrometry\u2010based label\u2010free quantitative proteomic analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>MSI showed distinct lipid profiles, namely, phosphatidylserines were more abundant in PET+ samples in both the neocortex and hippocampus. Proteomic analysis showed significant differences between TLE and nonepileptic postmortem controls involving pathways in neuron excitability and neurotransmitter transporters, which were upregulated in TLE. Compared to PET\u2212, all PET+ specimens displayed significantly dysregulated calcium signaling. Additionally, the neocortex of PET+ patients showed a shift from mitochondrial to cytosolic (cytoplasm of the cell) processes, whereas the hippocampus was characterized by a disruption of glycosylation and polyamine metabolism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>The applied spatial omics approach demonstrated localized molecular differences between metabolic subtypes of TLE patients. These findings may further specify these TLE subtypes and provide leads for targeted treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/epi.18366","type":"journal-article","created":{"date-parts":[[2025,3,20]],"date-time":"2025-03-20T09:58:18Z","timestamp":1742464698000},"page":"2538-2553","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Toward molecular phenotyping of temporal lobe epilepsy by spatial omics"],"prefix":"10.1111","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8355-9704","authenticated-orcid":false,"given":"Isabeau","family":"Vermeulen","sequence":"first","affiliation":[{"name":"Maastricht MultiModal Molecular Imaging Institute, Maastricht University  Maastricht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronny","family":"Mohren","sequence":"additional","affiliation":[{"name":"Maastricht MultiModal Molecular Imaging Institute, Maastricht University  Maastricht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micca","family":"Neusinger","sequence":"additional","affiliation":[{"name":"Maastricht MultiModal Molecular Imaging Institute, Maastricht University  Maastricht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1635-361X","authenticated-orcid":false,"given":"Tobias A.","family":"Dancker","sequence":"additional","affiliation":[{"name":"Maastricht MultiModal Molecular Imaging Institute, Maastricht University  Maastricht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michiel","family":"Vandenbosch","sequence":"additional","affiliation":[{"name":"Maastricht MultiModal Molecular Imaging Institute, Maastricht University  Maastricht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Beckervordersandforth","sequence":"additional","affiliation":[{"name":"GROW\u2013School for Oncology and Reproduction Maastricht University  Maastricht the Netherlands"},{"name":"Department of Pathology Maastricht University Medical Center  Maastricht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Balluff","sequence":"additional","affiliation":[{"name":"Maastricht MultiModal Molecular Imaging Institute, Maastricht University  Maastricht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rianna P.","family":"Van der Hel","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Maastricht University Medical Center  Maastricht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olaf E. 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