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Graph\u2010theoretical analysis quantified global and local network topology, and machine\u2010learning models assessed their values in patient identification and epileptogenic lateralization, with performance further evaluated in an independent validation dataset. Further connectome\u2013transcriptome association analyses linked these macroscale topological abnormalities to the microscale substrates in specific gene expressions, biological pathways, cellular compositions, and neurodevelopmental windows.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Patients exhibited global small\u2010worldness increase and local nodal reorganizations, with hyper\u2010connectivity in default mode and limbic networks and hypo\u2010connectivity in temporo\u2010occipital cortex. These MSN\u2010topology abnormalities enabled accurate patient classification (77.4%) and epileptogenic lateralization (83.2%), driven predominantly by features from limbic network (40.0% and 41.1%, respectively). These performances were reproducible in an independent validation dataset (classification accuracy\u2009=\u200975.4%, lateralization accuracy\u2009=\u200977.1%). Spatial transcriptomics mapped the MSN\u2010topology alterations to expression of genes enriched in RNA processing and mitochondrial energy metabolism, including key epilepsy risk genes such as\n                      <jats:italic>DNM1<\/jats:italic>\n                      and\n                      <jats:italic>PPFIA3<\/jats:italic>\n                      . These genes showed enriched expression in excitatory neurons, astrocytes, and oligodendrocytes, peaking during neurodevelopment in early\u2010fetal striatum and neonatal\u2010to\u2010childhood cortex.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>MSN topology delineates the pattern of cortical network reorganization in mTLE\u2010HS, aiding in patient identification and lateralization. The convergence of these macroscale connectomic alterations with microscale transcriptomic profiles points to an RNA\u2013metabolic interplay that shapes cortical vulnerability of mTLE\u2010HS in a progressive way.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/epi.70223","type":"journal-article","created":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T13:05:54Z","timestamp":1775135154000},"page":"3533-3549","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Transcriptional signatures and topological reorganization of morphometric similarity networks in temporal lobe epilepsy with unilateral hippocampal sclerosis"],"prefix":"10.1002","volume":"67","author":[{"given":"Fei","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Radiology, Huaxi MR Research Center (HMRRC), Institute of Radiology and Medical Imaging West China Hospital of Sichuan University  Chengdu Sichuan 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Anesthesiology West China Second University Hospital, Sichuan University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology West China Hospital of Sichuan University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyang","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Radiology, Huaxi MR Research Center (HMRRC), Institute of Radiology and Medical Imaging West China Hospital of Sichuan University  Chengdu Sichuan China"},{"name":"Psychoradiology Key Laboratory of Sichuan Province West China Hospital of Sichuan University  Chengdu Sichuan China"},{"name":"Research Unit of Psychoradiology Chinese Academy of Medical Sciences  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Neurology West China Hospital of Sichuan University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunge","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Neurology West China Hospital of Sichuan University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menglian","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Science and Technology West China Hospital, Sichuan University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7101-4125","authenticated-orcid":false,"given":"Dong","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Neurology West China Hospital of Sichuan University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peilin","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of 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