title: Functional connectivity changes and their relationship with clinical disability and white matter integrity in patients with relapsing-remitting multiple sclerosis.
abstract: OBJECTIVE
  To define the pathological substrate underlying disability in multiple sclerosis by evaluating the relationship of resting-state functional connectivity with microstructural brain damage, as assessed by diffusion tensor imaging, and clinical impairments.
  
  
  METHODS
  Thirty relapsing-remitting patients and 24 controls underwent 3T-MRI; motor abilities were evaluated by using measures of walking speed, hand dexterity and balance capability, while information processing speed was evaluated by a paced auditory serial addiction task. Independent component analysis and tract-based spatial statistics were applied to RS-fMRI and diffusion tensor imaging data using FSL software. Group differences, after dual regression, and clinical correlations were modelled with General-Linear-Model and corrected for multiple comparisons.
  
  
  RESULTS
  Patients showed decreased functional connectivity in 5 of 11 resting-state-networks (cerebellar, executive-control, medial-visual, basal ganglia and sensorimotor), changes in inter-network correlations and widespread white matter microstructural damage. In multiple sclerosis, corpus callosum microstructural damage positively correlated with functional connectivity in cerebellar and auditory networks. Moreover, functional connectivity within the medial-visual network inversely correlated with information processing speed. White matter widespread microstructural damage inversely correlated with both the paced auditory serial addiction task and hand dexterity.
  
  
  CONCLUSIONS
  Despite the within-network functional connectivity decrease and the widespread microstructural damage, the inter-network functional connectivity changes suggest a global brain functional rearrangement in multiple sclerosis. The correlation between functional connectivity alterations and callosal damage uncovers a link between functional and structural connectivity. Finally, functional connectivity abnormalities affect information processing speed rather than motor abilities.
authors.affiliation: Department of Neurology and Psychiatry, Sapienza University, Rome, Italy emilia.sbardella@uniroma1.it.
authors.forename: Emilia
authors.initials: E
authors.lastname: Sbardella
authors.affiliation: Department of Neurology and Psychiatry, University of Rome, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Tona
authors.affiliation: Department of Neurology and Psychiatry, University of Rome, Italy.
authors.forename: N
authors.initials: N
authors.lastname: Petsas
authors.affiliation: Department of Neurology and Psychiatry, University of Rome, Italy.
authors.forename: N
authors.initials: N
authors.lastname: Upadhyay
authors.affiliation: Department of Neurology and Psychiatry, University of Rome, Italy.
authors.forename: M C
authors.initials: MC
authors.lastname: Piattella
authors.affiliation: Department of Neurology and Psychiatry, University of Rome, Italy.
authors.forename: N
authors.initials: N
authors.lastname: Filippini
authors.affiliation: Department of Neurology and Psychiatry, University of Rome, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Prosperini
authors.affiliation: Department of Neurology and Psychiatry, University of Rome, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Pozzilli
authors.affiliation: Department of Neurology and Psychiatry, University of Rome, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Pantano
mesh_terms: D000293:Adolescent; D000328:Adult; D003337:Corpus Callosum / Q000473:pathology*; D056324:Diffusion Tensor Imaging; D004185:Disability Evaluation; D056344:Executive Function; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009048:Motor Skills; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000473:pathology* / Q000503:physiopathology*; D009434:Neural Pathways / Q000503:physiopathology; D066127:White Matter / Q000473:pathology*; D055815:Young Adult
keywords: Multiple sclerosis; disability; functional connectivity; resting state; structural connectivity