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However, the functional connectivity reorganization of limbic nodes remains unknown. Serum neurofilament light chains (sNfL) are clinically linked with the disease severity and neurological disability of anti\u2010NMDAR encephalitis. However, the relationship between sNfL and limbic\u2010based functional architecture has not been explored. We consecutively recruited 20 convalescent patients with anti\u2010NMDAR encephalitis and 24 healthy controls from March 2018 to March 2021. Resting\u2010state functional MRI metrics, including fractional amplitude of low\u2010frequency fluctuation (fALFF), regional homogeneity (ReHo), and atlas\u2010based seed functional connectivity, were analyzed to investigate regional activities and functional connectivity alterations. Correlation analysis among functional connectivity, sNfL, Mini\u2010Mental State Examination (MMSE), and Montreal cognitive assessment outcomes were explored in patients. Compared with those of healthy controls, the fALFF and ReHo were consistently increased in regions of the posterior default mode network (DMN) hub, mainly the bilateral supramarginal gyrus and precuneus, in patients with anti\u2010NMDAR encephalitis (FWE\u2010corrected <jats:italic>p<\/jats:italic>\u00a0&lt;\u20090.05). Patients demonstrated disturbed functional organization characterized by reduced connectivity of the posterior DMN hub with the sensorimotor cortex and hypoconnectivity of the parahippocampal gyrus (PHG) with the right fusiform gyrus but extensively enhanced thalamocortical connectivity (FWE\u2010corrected <jats:italic>p<\/jats:italic>\u00a0&lt;\u20090.05). Furthermore, convalescent sNfL showed a positive correlation with enhanced thalamocortical connectivity (<jats:italic>r<\/jats:italic>\u00a0=\u20090.4659, <jats:italic>p<\/jats:italic>\u00a0=\u20090.0384). Onset sNfL with an independent linear correlation to convalescent MMSE performance (<jats:italic>B<\/jats:italic> coefficient, \u22120.013, 95% CI, \u22120.025\u2009~\u2009\u22120.002, <jats:italic>p<\/jats:italic>\u00a0=\u20090.0260) was positively correlated with intra\u2010DMN connectivity (<jats:italic>r<\/jats:italic>\u00a0=\u20090.8969, <jats:italic>p<\/jats:italic>\u00a0&lt;\u20090.0001) and limbic\u2010sensory connectivity (<jats:italic>r<\/jats:italic>\u00a0=\u20090.4866, <jats:italic>p<\/jats:italic>\u00a0=\u20090.0346 for hippocampus seed and <jats:italic>r<\/jats:italic>\u00a0=\u20090.5218, <jats:italic>p<\/jats:italic>\u00a0=\u20090.0220 for PHG seed). Patients with anti\u2010NMDAR encephalitis demonstrated disturbed functional organization with substantial thalamocortical hyperconnectivity, that was positively correlated with convalescent sNfL. Onset sNfL showed a positive correlation with intra\u2010DMN connectivity and limbic\u2010sensory connectivity.<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc15700-fig-0008-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p>","DOI":"10.1111\/jnc.15700","type":"journal-article","created":{"date-parts":[[2022,10,3]],"date-time":"2022-10-03T07:39:45Z","timestamp":1664782785000},"page":"210-225","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Serum neurofilament light chain is associated with disturbed limbic\u2010based functional connectivity in patients with <scp>anti\u2010NMDAR<\/scp> encephalitis"],"prefix":"10.1111","volume":"164","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9094-4691","authenticated-orcid":false,"given":"Xiaodong","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Neurology The Third Affiliated Hospital of Sun Yat\u2010sen University  Guangzhou Guangdong China"},{"name":"Department of Neurology The Seventh Affiliated Hospital, Sun Yat\u2010sen University  Shenzhen Guangdong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3134-364X","authenticated-orcid":false,"given":"Ling","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Radiology The Third Affiliated Hospital of Sun Yat\u2010sen University  Guangzhou Guangdong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0191-0087","authenticated-orcid":false,"given":"Fuhua","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Neurology The Third Affiliated Hospital of Sun Yat\u2010sen University  Guangzhou Guangdong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3005-6163","authenticated-orcid":false,"given":"Yuge","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology The Third Affiliated Hospital of Sun Yat\u2010sen University  Guangzhou Guangdong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1126-9895","authenticated-orcid":false,"given":"Zhengjia","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Psychology Sun Yat\u2010sen University  Guangzhou Guangdong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3201-707X","authenticated-orcid":false,"given":"Jinhui","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute for Brain Research and Rehabilitation, Guangdong Key Laboratory of Mental Health and Cognitive Science, Center for Studies of Psychological Application South China Normal University  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2768-1654","authenticated-orcid":false,"given":"Yaqing","family":"Shu","sequence":"additional","affiliation":[{"name":"Department of Neurology The Third Affiliated Hospital of Sun Yat\u2010sen University  Guangzhou Guangdong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0880-958X","authenticated-orcid":false,"given":"Wei","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Neurology The 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