Rocca, Maria A (34973365100)Maria A (34973365100)RoccaHidalgo de La Cruz, Milagros (57191190537)Milagros (57191190537)Hidalgo de La CruzValsasina, Paola (6506051299)Paola (6506051299)ValsasinaMesaros, Sarlota (7004307592)Sarlota (7004307592)MesarosMartinovic, Vanja (56925159700)Vanja (56925159700)MartinovicIvanovic, Jovana (57196371316)Jovana (57196371316)IvanovicDrulovic, Jelena (55886929900)Jelena (55886929900)DrulovicFilippi, Massimo (7202268530)Massimo (7202268530)Filippi2025-06-122025-06-122020https://doi.org/10.1177/1352458519837704https://www.scopus.com/inward/record.uri?eid=2-s2.0-85063326177&doi=10.1177%2f1352458519837704&partnerID=40&md5=f552eccd3e88b4d77db25165396cd089https://remedy.med.bg.ac.rs/handle/123456789/4922Background: The features of functional network connectivity reorganization at the earliest stages of MS have not been investigated yet. Objective: To combine static and dynamic analysis of resting state (RS) functional connectivity (FC) to identify mechanisms of clinical dysfunction and recovery occurring in clinically isolated syndrome (CIS) patients. Methods: RS functional magnetic resonance imaging (fMRI) and clinical data were prospectively acquired from 50 CIS patients and 13 healthy controls (HC) at baseline, month 12 and month 24. Between-group differences and longitudinal evolution of network FC were analysed across 41 functionally relevant networks. Results: At follow-up, 47 patients developed MS. Disability remained stable (and relatively low). CIS and HC exhibited two recurring RS FC states (states 1 and 2, showing low and high internetwork connectivity, respectively). At baseline, patients showed reduced state 2 connectivity strength in the default-mode and cerebellar networks, and no differences in global dynamism versus HC. A selective FC reduction in networks affected by the clinical attack was also detected. At follow-up, increased state 2 connectivity strength and global connectivity dynamism was observed in patients versus HC. Conclusion: Longitudinal FC modifications occurring relatively early in the course of multiple sclerosis may represent a protective mechanism contributing to preserve clinical function over time. © The Author(s), 2019.clinically isolated syndromedefault-mode networkdynamic functional network connectivitylongitudinalMultiple sclerosisresting state