{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:58:29Z","timestamp":1790618309436,"version":"4.1.0"},"reference-count":92,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"vor","delay-in-days":22,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100009592","name":"Beijing Municipal Science and Technology Commission, Adminitrative Commission of Zhongguancun Science Park","doi-asserted-by":"publisher","award":["Z221100007422016"],"award-info":[{"award-number":["Z221100007422016"]}],"id":[{"id":"10.13039\/501100009592","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Focal cortical dysplasia Type II (FCD II) is a major cause of drug\u2010resistant epilepsy in children. Somatic mosaic variants affecting the PI3K\u2013AKT\u2013mTOR pathway are implicated in a substantial proportion of cases. The links between genotype, cellular pathology, epileptogenic networks, and clinical outcome remain incompletely defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This review synthesizes evidence on somatic mTOR\u2013pathway variants, lesion development, pathological cell populations, circuit mechanisms, single\u2010cell and spatial multi\u2010omics approaches in FCD II.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The developmental timing, lineage distribution, and local expansion of somatic variants influence lesion extent and phenotypic heterogeneity. Dysmorphic neurons may contribute to epileptogenicity through altered intrinsic excitability and synaptic function, whereas balloon cells may predominantly affect local circuits through secretory and microenvironmental mechanisms. mTOR hyperactivation may also alter interneuron development, subtype specification, and synaptic connectivity, thereby disrupting excitation\u2010inhibition balance. Single\u2010cell and spatial approaches, including RNA velocity, pseudotime analysis, chromatin\u2010age inference, and somatic genotyping, provide tools to resolve pathological cell states and lineage trajectories.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>FCD II should be considered a mosaic developmental disorder involving both cell\u2010autonomous and non\u2010cell\u2010autonomous mechanisms. Integrating somatic variant detection with cellular, spatial, electrophysiological, and surgical outcomes from matched patient tissue may enable biologically meaningful stratification and support the development of novel therapies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.71170","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T07:49:50Z","timestamp":1790149790000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Focal Cortical Dysplasia Type\n                    <scp>II<\/scp>\n                    : Somatic Mutations, Molecular Mechanisms, and Integrative Multi\u2010Omics Framework"],"prefix":"10.1002","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-9257-1058","authenticated-orcid":false,"given":"Zesheng","family":"Li","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Xuanwu Hospital Capital Medical University  Beijing 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