Reduced dynamics of functional connectivity and cognitive impairment in multiple sclerosis

Alessandro d’Ambrosio, Paola Valsasina, Antonio Gallo, Nicola de Stefano, Deborah Pareto, Frederik Barkhof, Olga Ciccarelli, Christian Enzinger, Gioacchino Tedeschi, M. Laura Stromillo, Maria J. Arévalo, Hanneke E. Hulst, Nils Muhlert, Marisa Koini, Massimo Filippi, Maria A. Rocca

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43 Citations (Scopus)


Background: In multiple sclerosis (MS), abnormalities of brain network dynamics and their relevance for cognitive impairment have never been investigated. Objectives: The aim of this study was to assess the dynamic resting state (RS) functional connectivity (FC) on 62 relapsing-remitting MS patients and 65 sex-matched healthy controls enrolled at 7 European sites. Methods: MS patients underwent clinical and cognitive evaluation. Between-group network FC differences were evaluated using a dynamic approach (based on sliding-window correlation analysis) and grouping correlation matrices into recurrent FC states. Results: Dynamic FC analysis revealed, in healthy controls and MS patients, three recurrent FC states: two characterized by strong intra- and inter-network connectivity and one characterized by weak inter-network connectivity (State 3). A total of 23 MS patients were cognitively impaired (CI). Compared to cognitively preserved (CP), CI-MS patients had reduced RS-FC between subcortical and default-mode networks in the low-connectivity State 3 and lower dwell time (i.e. time spent in a given state) in the high-connectivity State 2. CI-MS patients also exhibited a lower number and a less frequent switching between meta-states, as well as a smaller distance traveled through connectivity states. Conclusion: Time-varying RS-FC was markedly less dynamic in CI- versus CP-MS patients, suggesting that slow inter-network connectivity contributes to cognitive dysfunction in MS.
Original languageEnglish
Pages (from-to)476-488
Number of pages13
Issue number4
Publication statusPublished - 1 Apr 2020


  • Cognitive impairment
  • brain dynamics
  • functional connectivity
  • functional magnetic resonance imaging
  • multiple sclerosis
  • resting state

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