Brain Structure and Function

, Volume 221, Issue 1, pp 115–131 | Cite as

Impaired functional integration in multiple sclerosis: a graph theory study

  • Maria A. Rocca
  • Paola Valsasina
  • Alessandro Meani
  • Andrea Falini
  • Giancarlo Comi
  • Massimo FilippiEmail author
Original Article


Aim of this study was to explore the topological organization of functional brain network connectivity in a large cohort of multiple sclerosis (MS) patients and to assess whether its disruption contributes to disease clinical manifestations. Graph theoretical analysis was applied to resting state fMRI data from 246 MS patients and 55 matched healthy controls (HC). Functional connectivity between 116 cortical and subcortical brain regions was estimated using a bivariate correlation analysis. Global network properties (network degree, global efficiency, hierarchy, path length and assortativity) were abnormal in MS patients vs HC, and contributed to distinguish cognitively impaired MS patients (34 %) from HC, but not the main MS clinical phenotypes. Compared to HC, MS patients also showed: (1) a loss of hubs in the superior frontal gyrus, precuneus and anterior cingulum in the left hemisphere; (2) a different lateralization of basal ganglia hubs (mostly located in the left hemisphere in HC, and in the right hemisphere in MS patients); and (3) a formation of hubs, not seen in HC, in the left temporal pole and cerebellum. MS patients also experienced a decreased nodal degree in the bilateral caudate nucleus and right cerebellum. Such a modification of regional network properties contributed to cognitive impairment and phenotypic variability of MS. An impairment of global integration (likely to reflect a reduced competence in information exchange between distant brain areas) occurs in MS and is associated with cognitive deficits. A regional redistribution of network properties contributes to cognitive status and phenotypic variability of these patients.


Multiple sclerosis Graph analysis Resting state fMRI Cognitive impairment Phenotype 



We wish to thank Dr. Sara Sala for her help in conducting the statistical analysis. This work has been partially supported by a grant from Fondazione Italiana Sclerosi Multipla (FISM/2011/R/19) and by a grant from Italian Ministry of Health (GR-2009-1529671).

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Maria A. Rocca
    • 1
    • 2
  • Paola Valsasina
    • 1
  • Alessandro Meani
    • 1
  • Andrea Falini
    • 3
    • 4
  • Giancarlo Comi
    • 2
  • Massimo Filippi
    • 1
    • 2
    Email author
  1. 1.Neuroimaging Research Unit, Division of Neuroscience, Institute of Experimental NeurologySan Raffaele Scientific Institute, Vita-Salute San Raffaele UniversityMilanItaly
  2. 2.Department of NeurologySan Raffaele Scientific Institute, Vita-Salute San Raffaele UniversityMilanItaly
  3. 3.Department of NeuroradiologySan Raffaele Scientific Institute, Vita-Salute San Raffaele UniversityMilanItaly
  4. 4.CERMACSan Raffaele Scientific Institute, Vita-Salute San Raffaele UniversityMilanItaly

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