{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T10:19:43Z","timestamp":1787998783025,"version":"build-2784847793"},"reference-count":57,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82271491"],"award-info":[{"award-number":["82271491"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["W2521183"],"award-info":[{"award-number":["W2521183"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Depression is the most common psychiatric comorbidity in temporal lobe epilepsy. It is not merely a psychological reaction to seizures; accumulating evidence supports a bidirectional relationship in which mood dysregulation may also precede drug resistance. Here, we tested whether dynamic limbic\u2013executive integration provides an in\u00a0vivo circuit\u2010level substrate for this reciprocity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We cross\u2010sectionally studied 82 patients with temporal lobe epilepsy (33 drug\u2010resistant, 49 drug\u2010responsive) and 50 healthy controls. The drug\u2010resistant state was defined according to International League Against Epilepsy (ILAE) criteria (failure of two appropriate and tolerated anti\u2010seizure medication regimens), and depression severity was indexed by Self\u2010Rating Depression Scale scores. Using resting\u2010state functional magnetic resonance imaging (rs\u2010fMRI), we quantified time\u2010varying large\u2010scale network coupling to characterize limbic interactions with the broader connectome. We then identified specific patterns of limbic disintegration and tested their clinical relevance with mediation models, asking whether limbic integration with executive systems statistically linked drug\u2010resistant state and depression severity bidirectionally. Finally, we spatially correlated network effects with normative positron emission tomography (PET)\u2013derived neurotransmitter receptor\/transporter maps and Allen Human Brain Atlas gene\u2010expression profiles, followed by pathway enrichment analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The drug\u2010resistant state was characterized by dynamic decoupling of the limbic network from dorsal attention and frontoparietal systems. Reduced limbic\u2013dorsal attention integration tracked depression severity and statistically mediated both the pathway from the drug\u2010resistant state to depression (indirect\u2009=\u20092.18, 95% confidence interval [CI]\u2009=\u20090.20\u20134.54) and the reverse pathway from depression to the drug\u2010resistant state (indirect\u2009=\u20090.022, 95% CI\u2009=\u20090.006\u20130.049). The spatial signature of limbic\u2013executive disintegration co\u2010localized with higher serotonin (5\u2010HT) 1B receptor (5\u2010HT1B) and lower dopamine D2 receptor distributions and was transcriptomically enriched for cellular stress adaptation and cell\u2010fate pathways, including translation reinitiation, telomerase activity, and tumor necrosis factor\u2010related apoptosis\u2010inducing ligand (TRAIL)\u2010mediated apoptotic signaling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>These convergent multi\u2010scale results propose a dynamic limbic\u2013executive disintegration model of the reciprocity between seizure intractability and depression. Our findings reframe comorbidity as coupled systems\u2010level dysfunction and motivate integrated stratification and target prioritization for dual\u2010burden\u2013focused neuromodulatory intervention.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/epi.70303","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T14:39:08Z","timestamp":1780411148000},"page":"4277-4291","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dynamic limbic\u2013executive decoupling underpins the reciprocal link between drug\u2010resistant state and depression in temporal lobe epilepsy"],"prefix":"10.1002","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-5449-8793","authenticated-orcid":false,"given":"Zhoukang","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Psychology, State Key Laboratory of Eye Health University of Science and Technology of China  Hefei Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2810-320X","authenticated-orcid":false,"given":"Haiyun","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Radiology Xiangya Hospital, Central South University  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6693-9537","authenticated-orcid":false,"given":"Liangjiecheng","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Psychology, State Key Laboratory of Eye Health University of Science and Technology of China  Hefei Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3072-0424","authenticated-orcid":false,"given":"Yaotian","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Psychology, State Key Laboratory of Eye Health University of Science and Technology of China  Hefei Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0560-1983","authenticated-orcid":false,"given":"Min","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Psychology, State Key Laboratory of Eye Health University of Science and Technology of China  Hefei Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aobo","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine University of Science and Technology of China  Hefei Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-3948-2107","authenticated-orcid":false,"given":"Mengyuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Psychology, State Key Laboratory of Eye Health University of Science and Technology of China  Hefei Anhui 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