title: Large-scale neuronal network dysfunction in relapsing-remitting multiple sclerosis.
abstract: OBJECTIVE
  Given that multiple sclerosis (MS) hits diffusely the brain hemispheres, we hypothesized that this should result in a distributed pattern of functional connectivity (FC) abnormalities. To this aim, we assessed, using resting-state (RS) fMRI, intrinsic FC and functional network connectivity (FNC) of brain large-scale neuronal networks from 85 patients with relapsing-remitting MS (RRMS) and 40 matched controls.
  
  
  METHODS
  Independent component analysis was used to analyze RS fMRI data. Intrinsic FC of each cluster of each RS network (RSN) was compared between controls and patients (analysis of variance adjusted for age, gender, and gray matter volume). The FNC toolbox was used to assess interactions among RSNs.
  
  
  RESULTS
  Compared to controls, patients with RRMS experienced a decreased RS FC in regions of the salience (SN), executive control (ECN), working memory (WMN), default mode (DMN), sensorimotor, and visual networks. They also had an increased RS FC in regions of the ECN and auditory RSN. Decreased RS FC was significantly correlated with disability and T2 lesion volumes. In patients with RRMS, when compared to controls, FNC analysis showed that the ECN had an increased connectivity with the SN and a decreased connectivity with the DMN. An abnormal connectivity between the WMNs and sensory networks was also found.
  
  
  CONCLUSIONS
  Functional abnormalities within and between large-scale neuronal networks occur in patients with RRMS and are related to the extent of T2 lesions and the severity of disability. Longitudinal studies should ascertain whether such functional abnormalities confer a systematic vulnerability to disease progression or, conversely, protect against the onset of clinical deficits.
authors.affiliation: Department of Neurology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Rocca
authors.forename: Paola
authors.initials: P
authors.lastname: Valsasina
authors.forename: Vittorio
authors.initials: V
authors.lastname: Martinelli
authors.forename: Paolo
authors.initials: P
authors.lastname: Misci
authors.forename: Andrea
authors.initials: A
authors.lastname: Falini
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Comi
authors.forename: Massimo
authors.initials: M
authors.lastname: Filippi
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001921:Brain / Q000098:blood supply / Q000503:physiopathology*; D001931:Brain Mapping; D004185:Disability Evaluation; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000473:pathology*; D009415:Nerve Net / Q000098:blood supply / Q000473:pathology; D009434:Neural Pathways / Q000098:blood supply* / Q000473:pathology; D010100:Oxygen / Q000097:blood; D025341:Principal Component Analysis; D013223:Statistics as Topic; D055815:Young Adult
chemical_list: D010100:Oxygen