title: Multiple sclerosis impairs regional functional connectivity in the cerebellum.
abstract: Resting-state functional magnetic resonance imaging (rs-fMRI) has been used to study changes in long-range functional brain connectivity in multiple sclerosis (MS). Yet little is known about how MS affects functional brain connectivity at the local level. Here we studied 42 patients with MS and 30 matched healthy controls with whole-brain rs-fMRI at 3 T to examine local functional connectivity. Using the Kendall's Coefficient of Concordance, regional homogeneity of blood-oxygen-level-dependent (BOLD)-signal fluctuations was calculated for each voxel and used as a measure of local connectivity. Patients with MS showed a decrease in regional homogeneity in the upper left cerebellar hemisphere in lobules V and VI relative to healthy controls. Similar trend changes in regional homogeneity were present in the right cerebellar hemisphere. The results indicate a disintegration of regional processing in the cerebellum in MS. This might be caused by a functional disruption of cortico-ponto-cerebellar and spino-cerebellar inputs, since patients with higher lesion load in the left cerebellar peduncles showed a stronger reduction in cerebellar homogeneity. In patients, two clusters in the left posterior cerebellum expressed a reduction in regional homogeneity with increasing global disability as reflected by the Expanded Disability Status Scale (EDSS) score or higher ataxia scores. The two clusters were mainly located in Crus I and extended into Crus II and the dentate nucleus but with little spatial overlap. These findings suggest a link between impaired regional integration in the cerebellum and general disability and ataxia.
authors.affiliation: Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Kettegaard Allé 30, 2650 Hvidovre, Denmark.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Dogonowski
authors.affiliation: Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Kettegaard Allé 30, 2650 Hvidovre, Denmark ; Cognitive Systems, Department of Applied Mathematics and Computer Science, Technical University of Denmark, Matematiktorvet, Building 321, 2800 Lyngby, Denmark.
authors.forename: Kasper Winther
authors.initials: KW
authors.lastname: Andersen
authors.affiliation: Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Kettegaard Allé 30, 2650 Hvidovre, Denmark ; Cognitive Systems, Department of Applied Mathematics and Computer Science, Technical University of Denmark, Matematiktorvet, Building 321, 2800 Lyngby, Denmark.
authors.forename: Kristoffer Hougaard
authors.initials: KH
authors.lastname: Madsen
authors.affiliation: Danish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital Rigshospitalet, Blegdamsvej 9, 2100 København Ø, Denmark.
authors.forename: Per Soelberg
authors.initials: PS
authors.lastname: Sørensen
authors.affiliation: Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Kettegaard Allé 30, 2650 Hvidovre, Denmark ; Neurobiology Research Unit, Copenhagen University Hospital Rigshospitalet, Juliane Maries Vej 24, Building 9201, 2100 København Ø, Denmark.
authors.forename: Olaf Bjarne
authors.initials: OB
authors.lastname: Paulson
authors.affiliation: Danish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital Rigshospitalet, Blegdamsvej 9, 2100 København Ø, Denmark.
authors.forename: Morten
authors.initials: M
authors.lastname: Blinkenberg
authors.affiliation: Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Kettegaard Allé 30, 2650 Hvidovre, Denmark.
authors.forename: Hartwig Roman
authors.initials: HR
authors.lastname: Siebner
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002531:Cerebellum / Q000098:blood supply / Q000473:pathology* / Q000503:physiopathology; D004185:Disability Evaluation; D005260:Female; D007839:Functional Laterality; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000473:pathology*; D009434:Neural Pathways / Q000098:blood supply / Q000502:physiology*; D010100:Oxygen / Q000097:blood; D012044:Regression Analysis; D012146:Rest; D013223:Statistics as Topic; D055815:Young Adult
chemical_list: D010100:Oxygen
keywords: Cerebellum; Multiple sclerosis; Regional connectivity; Resting-state; fMRI