Abstract
Objective: To investigate whether the structural connectivity of the brain's rich-club organization is altered in patients with primary progressive MS and whether such changes to this fundamental network feature are associated with disability measures.
Methods: We recruited 37 patients with primary progressive MS and 21 healthy controls for an observational cohort study. Structural connectomes were reconstructed based on diffusion-weighted imaging data using probabilistic tractography and analyzed with graph theory.
Results: We observed the same topological organization of brain networks in patients and controls. Consistent with the originally defined rich-club regions, we identified superior frontal, precuneus, superior parietal, and insular cortex in both hemispheres as rich-club nodes. Connectivity within the rich club was significantly reduced in patients with MS (p = 0.039). The extent of reduced rich-club connectivity correlated with clinical measurements of mobility (Kendall rank correlation coefficient τ = −0.20, p = 0.047), hand function (τ = −0.26, p = 0.014), and information processing speed (τ = −0.20, p = 0.049).
Conclusions: In patients with primary progressive MS, the fundamental organization of the structural connectome in rich-club and peripheral nodes was preserved and did not differ from healthy controls. The proportion of rich-club connections was altered and correlated with disability measures. Thus, the rich-club organization of the brain may be a promising network phenotype for understanding the patterns and mechanisms of neurodegeneration in MS.
GLOSSARY
- APL=
- average shortest path length;
- EDSS=
- Expanded Disability Status Scale;
- FDR=
- false discovery rate;
- FSL=
- functional imaging software library;
- HC=
- healthy control;
- MANCOVA=
- multivariate analysis of covariance;
- MSFC=
- multiple sclerosis functional composite;
- NHPT=
- Nine-Hole Peg Test;
- PPMS=
- primary progressive MS;
- RRMS=
- relapsing-remitting MS;
- SDMT=
- Symbol Digit Modalities Test;
- SWI=
- small-world index;
- T25FW=
- timed 25-foot walk
Footnotes
↵* These authors contributed equally to this work.
Funding information and disclosures are provided at the end of the article. Go to Neurology.org/nn for full disclosure forms. The Article Processing Charge was funded by the authors.
Supplemental data at Neurology.org/nn
- Received December 12, 2016.
- Accepted in final form May 17, 2017.
- Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology
This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
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