Cognitive dysfunction in early multiple sclerosis: altered centrality derived from resting-state functional connectivity using magneto-encephalography

PLoS One. 2012;7(7):e42087. doi: 10.1371/journal.pone.0042087. Epub 2012 Jul 27.

Abstract

Background: Cognitive dysfunction in multiple sclerosis (MS) is frequent. Insight into underlying mechanisms would help to develop therapeutic strategies.

Objective: To explore the relationship of cognitive performance to patterns of nodal centrality derived from magneto-encephalography (MEG).

Methods: 34 early relapsing-remitting MS patients (median EDSS 2.0) and 28 age- and gender-matched healthy controls (HC) had a MEG, a neuropsychological assessment and structural MRI. Resting-state functional connectivity was determined by the synchronization likelihood. Eigenvector Centrality (EC) was used to quantify for each sensor its connectivity and importance within the network. A cognition-score was calculated, and normalized grey and white matter volumes were determined. EC was compared per sensor and frequency band between groups using permutation testing, and related to cognition.

Results: Patients had lower grey and white matter volumes than HC, male patients lower cognitive performance than female patients. In HC, EC distribution showed highest nodal centrality over bi-parietal sensors ("hubs"). In patients, nodal centrality was even higher bi-parietally (theta-band) but markedly lower left temporally (upper alpha- and beta-band). Lower cognitive performance correlated to decreased nodal centrality over left temporal (lower alpha-band) and right temporal (beta-band) sensors, and to increased nodal centrality over right parieto-temporal sensors (beta-band). Network changes were most pronounced in male patients.

Conclusions: Partial functional disconnection of the temporal regions was associated with cognitive dysfunction in MS; increased centrality in parietal hubs may reflect a shift from temporal to possibly less efficient parietal processing. To better understand patterns and dynamics of these network changes, longitudinal studies are warranted, also addressing the influence of gender.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Case-Control Studies
  • Cognition Disorders / complications
  • Cognition Disorders / pathology*
  • Cognition Disorders / physiopathology*
  • Cognition Disorders / psychology
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Magnetoencephalography*
  • Male
  • Multiple Sclerosis / complications
  • Nerve Net / pathology*
  • Nerve Net / physiopathology*
  • Neuropsychological Tests
  • Rest*

Grants and funding

The study was sponsored by a grant of the Dutch Multiple Sclerosis Research Foundation (Contract grant numbers: 02-358b, 05-358c and 08-650). MH was sponsored by the Swiss National Science Foundation (SPUM-33CM30-124115) and the Swiss Multiple Sclerosis Society. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.