title: Working memory network dysfunction in relapse-onset multiple sclerosis phenotypes: A clinical-imaging evaluation.
abstract: OBJECTIVE
  We investigated clinical, behavioural and functional magnetic resonance imaging (fMRI) correlates of working memory load in relapse-onset multiple sclerosis (MS) patients.
  
  
  METHODS
  In total, 12 clinically isolated syndromes (CIS) patients at risk of MS, 38 relapsing-remitting multiple sclerosis (RRMS), 22 secondary progressive multiple sclerosis (SPMS) and 24 healthy controls (HC) performed an N-back fMRI task. Correlations between fMRI abnormalities and clinico-behavioural and structural magnetic resonance imaging (MRI) measures were assessed.
  
  
  RESULTS
  Participants activated brain regions of the working memory network, especially in fronto-parietal lobes and cerebellum, and deactivated areas of the default mode network (DMN). During the N-back load contrast, compared to HC, the three groups of MS patients had a common pattern of decreased activation of the right superior parietal lobule, left inferior parietal lobule and left middle frontal gyrus. Areas specifically more active in CIS patients compared to the other study groups were found in the left medial superior frontal gyrus and right anterior cingulate cortex, whereas SPMS patients selectively activated the left parahippocampal gyrus and left superior temporal pole (STP). Worse accuracy and global cognitive scores correlated with increased STP activation.
  
  
  CONCLUSIONS
  Load-dependent alterations of working memory network recruitment occur in MS. Frontal hyperactivation is maintained in CIS and lost in SPMS. Abnormal recruitment of DMN areas is related to worse cognitive and behavioural outcomes.
authors.affiliation: Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Vacchi
authors.affiliation: Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy/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.affiliation: Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Meani
authors.affiliation: Department of Neurology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Mariaemma
authors.initials: M
authors.lastname: Rodegher
authors.affiliation: Department of Neurology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Martinelli
authors.affiliation: Department of Neurology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Comi
authors.affiliation: Department of Neuroradiology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Falini
authors.affiliation: Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy/Department of Neurology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Filippi
mesh_terms: D000293:Adolescent; D000328:Adult; D001921:Brain / Q000473:pathology* / Q000503:physiopathology; D001931:Brain Mapping; D002531:Cerebellum / Q000473:pathology; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008570:Memory, Short-Term / Q000502:physiology*; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000473:pathology*; D009415:Nerve Net / Q000473:pathology*; D010641:Phenotype; D055815:Young Adult
keywords: Multiple sclerosis; N-back; attentive-executive domain; clinical phenotypes; default mode network; fMRI