title: Gender-related differences in functional connectivity in multiple sclerosis.
abstract: BACKGROUND
  Gender effects are strong in multiple sclerosis (MS), with male patients showing a worse clinical outcome than female patients. Functional reorganization of neural activity may contribute to limit disability, and possible gender differences in this process may have important clinical implications.
  
  
  OBJECTIVE
  The aim of this study was to explore gender-related changes in functional connectivity and network efficiency in MS patients. Additionally, we explored the association of functional changes with cognitive function.
  
  
  METHODS
  Sixty subjects were included in the study, matched for age, education level and intelligence quotient (IQ). Male and female patients were matched for disability, disease duration and white matter lesion load. Two cognitive domains often impaired in MS, i.e. visuospatial memory and information processing speed, were evaluated in all subjects. Functional connectivity between brain regions and network efficiency was explored using resting-state functional magnetic resonance imaging and graph analysis. Differences in cognitive and functional characteristics between groups, and correlations with cognitive performance, were examined.
  
  
  RESULTS
  Male patients showed worse performance on cognitive tests than female and male controls, while female patients were cognitively normal. Decreases in functional connectivity and network efficiency, observed in male patients, correlated with reduced visuospatial memory (r = -0.6 and r = -0.5, respectively). In the control group, no cognitive differences were found between genders, despite differences in functional connectivity between healthy men and women.
  
  
  CONCLUSIONS
  Functional connectivity differences were found in male patients only and were related to impaired visuospatial memory. These results underline the importance of gender in MS and require further investigation in larger and longitudinal studies.
authors: Department of Radiology, VU University Medical Center, Amsterdam, The Netherlands. m.schoonheim@vumc.nl
authors: Menno M
authors: MM
authors: Schoonheim
authors: Hanneke E
authors: HE
authors: Hulst
authors: Doriana
authors: D
authors: Landi
authors: Olga
authors: O
authors: Ciccarelli
authors: Stefan D
authors: SD
authors: Roosendaal
authors: Ernesto J
authors: EJ
authors: Sanz-Arigita
authors: Hugo
authors: H
authors: Vrenken
authors: Chris H
authors: CH
authors: Polman
authors: Cornelis J
authors: CJ
authors: Stam
authors: Frederik
authors: F
authors: Barkhof
authors: Jeroen J G
authors: JJ
authors: Geurts
mesh_terms: D000328:Adult; D003071:Cognition / Q000502:physiology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008568:Memory / Q000502:physiology; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000503:physiopathology*; D009415:Nerve Net / Q000503:physiopathology*; D012146:Rest / Q000502:physiology; D012727:Sex Characteristics; D013028:Space Perception / Q000502:physiology