title: Functional magnetic resonance imaging correlates of cognitive performance in patients with a clinically isolated syndrome suggestive of multiple sclerosis at presentation: an activation and connectivity study.
abstract: OBJECTIVE
  To assess whether abnormalities on functional magnetic resonance imaging (fMRI) are related to cognitive function in patients at presentation with clinically isolated syndrome (CIS) suggestive of multiple sclerosis.
  
  
  METHODS
  Eighteen patients with CIS and 15 healthy controls (HCs) performed an adapted fMRI version of the Paced Auditory Serial Addition Test (PASAT). According to their PASAT performance, CIS patients were divided into two groups: 10 with a low PASAT performance (<1 SD from the mean value of HCs) were considered 'cognitive impairment' (CI); eight patients were defined as 'cognitively preserved' (CP). Between-group differences in the patterns of brain activations and effective connectivity were assessed.
  
  
  RESULTS
  During PASAT, compared to HCs, CIS patients showed increased activations of the bilateral inferior parietal lobe (IPL), bilateral precuneus, bilateral middle frontal gyrus (MFG), left anterior cingulate cortex (ACC), left claustrum, right thalamus and right caudate nucleus. When CIS patients were analyzed, the CI group had a more significant activation of the bilateral IPL than HCs and CP patients. Compared to CP patients, they also had more significant recruitment of the right superior parietal lobe, right cerebellum, left MFG and left ACC. The analysis of effective connectivity showed stronger connections between several regions of the right hemisphere involved in working memory function in CI patients versus CP and HC.
  
  
  CONCLUSIONS
  During performance of the PASAT, CIS patients show abnormalities in the patterns of cortical recruitment and connectivity related to the level of their cognitive impairment.
authors.affiliation: Division of Neuroscience, Scientific Institute and Vita-Salute University, Hospital San Raffaele, Milan, Italy. forn@psb.uji.es
authors.forename: C
authors.initials: C
authors.lastname: Forn
authors.forename: M A
authors.initials: MA
authors.lastname: Rocca
authors.forename: P
authors.initials: P
authors.lastname: Valsasina
authors.forename: I
authors.initials: I
authors.lastname: Boscá
authors.forename: B
authors.initials: B
authors.lastname: Casanova
authors.forename: A
authors.initials: A
authors.lastname: Sanjuan
authors.forename: C
authors.initials: C
authors.lastname: Ávila
authors.forename: M
authors.initials: M
authors.lastname: Filippi
mesh_terms: D000293:Adolescent; D000328:Adult; D001499:Bayes Theorem; D002421:Caudate Nucleus / Q000503:physiopathology; D002531:Cerebellum / Q000503:physiopathology; D003071:Cognition / Q000502:physiology*; D005260:Female; D006179:Gyrus Cinguli / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D008959:Models, Neurological; D009103:Multiple Sclerosis / Q000503:physiopathology* / Q000523:psychology; D009415:Nerve Net / Q000503:physiopathology*; D010296:Parietal Lobe / Q000503:physiopathology; D013788:Thalamus / Q000503:physiopathology; D055815:Young Adult