Increased functional connectivity indicates the severity of cognitive impairment in multiple sclerosis

David J. Hawellek, Joerg F. Hipp, Christopher M. Lewis, Maurizio Corbetta, Andreas K. Engel

Research output: Contribution to journalArticlepeer-review

195 Scopus citations


Correlations in spontaneous brain activity provide powerful access to large-scale organizational principles of the CNS. However, making inferences about cognitive processes requires a detailed understanding of the link between these couplings and the structural integrity of the CNS. We studied the impact of multiple sclerosis, which leads to the severe disintegration of the central white matter, on functional connectivity patterns in spontaneous cortical activity. Using a data driven approach based on the strength of a salient pattern of cognitive pathology, we identified distinct networks that exhibit increases in functional connectivity despite the presence of strong and diffuse reductions of the central white-matter integrity. The default mode network emerged as a core target of these connectivity modulations, showing enhanced functional coupling in bilateral inferior parietal cortex, posterior cingulate, and medial prefrontal cortex. These findings imply a complex and diverging relation of anatomical and functional connectivity in early multiple sclerosis and, thus, add an important observation for understanding how cognitive abilities and CNS integrity may be reflected in the intrinsic covariance of functional signals.

Original languageEnglish
Pages (from-to)19066-19071
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number47
StatePublished - Nov 22 2011


  • Diffusion tensor imaging
  • Fractional anisotropy
  • Neurological
  • Resting state


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