Increased structural white and grey matter network connectivity compensates for functional decline in early multiple sclerosis

Vinzenz Fleischer, Adriane Gröger, Nabin Koirala, Amgad Droby, Muthuraman Muthuraman, Pierre Kolber, Eva Reuter, Sven G. Meuth, Frauke Zipp, Sergiu Groppa

Research output: Contribution to journalArticlepeer-review


Background: The pathology of multiple sclerosis (MS) consists of demyelination and neuronal injury, which occur early in the disease; yet, remission phases indicate repair. Whether and how the central nervous system (CNS) maintains homeostasis to counteract clinical impairment is not known. Objective: We analyse the structural connectivity of white matter (WM) and grey matter (GM) networks to understand the absence of clinical decline as the disease progresses. Methods: A total of 138 relapsing-remitting MS patients (classified into six groups by disease duration) and 32 healthy controls were investigated using 3-Tesla magnetic resonance imaging (MRI). Networks were analysed using graph theoretical approaches based on connectivity patterns derived from diffusion-tensor imaging with probabilistic tractography for WM and voxel-based morphometry and regional-volume-correlation matrix for GM. Results: In the first year after disease onset, WM networks evolved to a structure of increased modularity, strengthened local connectivity and increased local clustering while no clinical decline occurred. GM networks showed a similar dynamic of increasing modularity. This modified connectivity pattern mainly involved the cerebellum, cingulum and temporo-parietal regions. Clinical impairment was associated at later disease stages with a divergence of the network patterns. Conclusion: Our findings suggest that network functionality in MS is maintained through structural adaptation towards increased local and modular connectivity, patterns linked to adaptability and homeostasis.

Original languageEnglish
Pages (from-to)432-441
Number of pages10
JournalMultiple Sclerosis Journal
Issue number3
StatePublished - 1 Mar 2017
Externally publishedYes


  • Structural network reorganization
  • adaptation
  • connectivity
  • early multiple sclerosis
  • modularity
  • network dynamics


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