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

Mult Scler. 2017 Mar;23(3):432-441. doi: 10.1177/1352458516651503. Epub 2016 Jul 11.


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.

Keywords: Structural network reorganization; adaptation; connectivity; early multiple sclerosis; modularity; network dynamics.

MeSH terms

  • Adult
  • Demyelinating Diseases / pathology
  • Diffusion Tensor Imaging / methods
  • Female
  • Gray Matter / pathology*
  • Humans
  • Image Processing, Computer-Assisted / methods
  • Male
  • Middle Aged
  • Multiple Sclerosis / pathology*
  • Nerve Fibers, Myelinated / pathology
  • Nerve Net / pathology*
  • White Matter / pathology*
  • Young Adult