title: Increased structural white and grey matter network connectivity compensates for functional decline in early multiple sclerosis.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Neurology and Neuroimaging Center (NIC), Focus Program Translational Neuroscience (FTN), Rhine-Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Vinzenz
authors.initials: V
authors.lastname: Fleischer
authors.affiliation: Department of Neurology and Neuroimaging Center (NIC), Focus Program Translational Neuroscience (FTN), Rhine-Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Adriane
authors.initials: A
authors.lastname: Gröger
authors.affiliation: Department of Neurology and Neuroimaging Center (NIC), Focus Program Translational Neuroscience (FTN), Rhine-Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Nabin
authors.initials: N
authors.lastname: Koirala
authors.affiliation: Department of Neurology and Neuroimaging Center (NIC), Focus Program Translational Neuroscience (FTN), Rhine-Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Amgad
authors.initials: A
authors.lastname: Droby
authors.affiliation: Department of Neurology and Neuroimaging Center (NIC), Focus Program Translational Neuroscience (FTN), Rhine-Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Muthuraman
authors.initials: M
authors.lastname: Muthuraman
authors.affiliation: Department of Neurology and Neuroimaging Center (NIC), Focus Program Translational Neuroscience (FTN), Rhine-Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Pierre
authors.initials: P
authors.lastname: Kolber
authors.affiliation: Department of Neurology and Neuroimaging Center (NIC), Focus Program Translational Neuroscience (FTN), Rhine-Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Reuter
authors.affiliation: Department of Neurology, University of Münster, Münster, Germany.
authors.forename: Sven G
authors.initials: SG
authors.lastname: Meuth
authors.affiliation: Department of Neurology and Neuroimaging Center (NIC), Focus Program Translational Neuroscience (FTN), Rhine-Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Frauke
authors.initials: F
authors.lastname: Zipp
authors.affiliation: Department of Neurology and Neuroimaging Center (NIC), Focus Program Translational Neuroscience (FTN), Rhine-Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Sergiu
authors.initials: S
authors.lastname: Groppa
mesh_terms: D000328:Adult; D003711:Demyelinating Diseases / Q000473:pathology; D056324:Diffusion Tensor Imaging / Q000379:methods; D005260:Female; D066128:Gray Matter / Q000473:pathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000473:pathology*; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D009415:Nerve Net / Q000473:pathology*; D066127:White Matter / Q000473:pathology*; D055815:Young Adult
keywords: Structural network reorganization; adaptation; connectivity; early multiple sclerosis; modularity; network dynamics