title: Default-mode network dysfunction and cognitive impairment in progressive MS.
abstract: OBJECTIVE
  This study explores default-mode network (DMN) abnormalities in patients with secondary progressive (SP) and primary progressive (PP) multiple sclerosis (MS) and whether such abnormalities correlate with cognitive impairment and damage to selected white matter (WM) fiber bundles, quantified using diffusion tensor (DT) MRI tractography.
  
  
  METHODS
  Resting state (RS) functional MRI and DT MRI data were acquired from 33 patients with SPMS, 24 patients with PPMS, and 24 controls. Independent component analysis (ICA) was used to identify the DMN. SPM5 was used to assess within- and between-group activations.
  
  
  RESULTS
  Between-group differences in DMN activity were found in the left medial prefrontal cortex (mPFC), left precentral gyrus (PcG), and anterior cingulate cortex (ACC). Compared to controls, patients with SPMS had reduced activity in the mPFC (p = 0.01) and PcG (p = 0.02), while patients with PPMS had reduced activity in the PcG (p = 0.008) and the ACC (p = 0.002). Compared to patients with PPMS, patients with SPMS had increased ACC activity (p = 0.04). Reduction of RS activity in the ACC was more pronounced in cognitively impaired vs cognitively preserved patients with MS (p = 0.02). In patients with MS, DMN abnormalities correlated with the PASAT and word list test scores (r values ranging from 0.35 to 0.45) and DT MRI changes in the corpus callosum and the cingulum (r values ranging from 0.82 to 0.87).
  
  
  CONCLUSIONS
  These results suggest that a dysfunction of the anterior components of the default-mode network may be among the factors responsible for the accumulation of cognitive deficits in patients with progressive multiple sclerosis.
authors.affiliation: Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, Scientific Institute and University Ospedale San Raffaele, Milan, Italy.
authors.forename: M A
authors.initials: MA
authors.lastname: Rocca
authors.forename: P
authors.initials: P
authors.lastname: Valsasina
authors.forename: M
authors.initials: M
authors.lastname: Absinta
authors.forename: G
authors.initials: G
authors.lastname: Riccitelli
authors.forename: M E
authors.initials: ME
authors.lastname: Rodegher
authors.forename: P
authors.initials: P
authors.lastname: Misci
authors.forename: P
authors.initials: P
authors.lastname: Rossi
authors.forename: A
authors.initials: A
authors.lastname: Falini
authors.forename: G
authors.initials: G
authors.lastname: Comi
authors.forename: M
authors.initials: M
authors.lastname: Filippi
mesh_terms: D000328:Adult; D000368:Aged; D001921:Brain / Q000473:pathology / Q000503:physiopathology*; D001931:Brain Mapping; D003072:Cognition Disorders / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D056324:Diffusion Tensor Imaging; D004185:Disability Evaluation; D018450:Disease Progression; D005260:Female; D007839:Functional Laterality / Q000502:physiology; D006179:Gyrus Cinguli / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000473:pathology / Q000503:physiopathology; D020528:Multiple Sclerosis, Chronic Progressive / Q000473:pathology / Q000503:physiopathology* / Q000523:psychology; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D009415:Nerve Net / Q000473:pathology / Q000503:physiopathology*; D009483:Neuropsychological Tests; D011237:Predictive Value of Tests; D017397:Prefrontal Cortex / Q000473:pathology / Q000503:physiopathology; D011379:Prognosis; D012680:Sensitivity and Specificity; D055815:Young Adult