Structural constraints of functional connectivity drive cognitive impairment in the early stages of multiple sclerosis

Ismail Koubiyr, Mathilde Deloire, Bruno Brochet*, Pierre Besson, Julie Charré-Morin, Aurore Saubusse, Thomas Tourdias, Aurélie Ruet

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


Background: The relationship between structural and functional deficits in multiple sclerosis (MS) is unclear. Objective: This study explored structure-function relationships during the 5 years following a clinically isolated syndrome and their role in cognitive performance. Methods: Thirty-two patients were enrolled after their first neurological episode suggestive of MS and followed for 5 years, along with 10 matched healthy controls. We assessed structural (using diffusion tensor imaging) and functional (using resting-state functional magnetic resonance imaging (fMRI)) brain network metrics, clinical and cognitive scores at each follow-up visit. Structural–functional coupling, calculated as the correlation coefficient between strengths of structural and functional networks, was used to assess structure–function relationships. Results: Structural clustering coefficient was significantly increased after 5 years, whereas characteristic path length decreased. Structural connections decreased after 1 year and increased after 5 years. Functional connections and related path lengths were decreased after 5 years. Structural–functional coupling had increased significantly after 5 years. This structural–functional coupling was associated with cognitive and clinical evolution, with stronger coupling associated with a decline in both domains. Conclusion: Our findings provide novel biological evidence that MS leads to a more constrained anatomical-dependant functional connectivity. The collapse of this network seems to lead to both cognitive worsening and clinical disability.

Original languageEnglish (US)
Pages (from-to)559-567
Number of pages9
JournalMultiple Sclerosis Journal
Issue number4
StatePublished - Apr 2021


  • Multiple sclerosis
  • clinically isolated syndrome
  • cognition
  • diffusion tensor imaging
  • functional MRI
  • graph theory

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


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