Experimental Brain Research

, Volume 187, Issue 1, pp 25–31

Impairment of movement-associated brain deactivation in multiple sclerosis: further evidence for a functional pathology of interhemispheric neuronal inhibition

  • S. C. Manson
  • C. Wegner
  • M. Filippi
  • F. Barkhof
  • C. Beckmann
  • O. Ciccarelli
  • N. De Stefano
  • Christian Enzinger
  • F. Fazekas
  • F. Agosta
  • A. Gass
  • J. Hirsch
  • H. Johansen-Berg
  • L. Kappos
  • T. Korteweg
  • C. Polman
  • L. Mancini
  • F. Manfredonia
  • S. Marino
  • D. H. Miller
  • X. Montalban
  • J. Palace
  • M. Rocca
  • S. Ropele
  • A. Rovira
  • S. Smith
  • A. Thompson
  • J. Thornton
  • T. Yousry
  • J. A. Frank
  • P. M. Matthews
Research Article

DOI: 10.1007/s00221-008-1276-1

Cite this article as:
Manson, S.C., Wegner, C., Filippi, M. et al. Exp Brain Res (2008) 187: 25. doi:10.1007/s00221-008-1276-1

Abstract

Motor control demands coordinated excitation and inhibition across distributed brain neuronal networks. Recent work has suggested that multiple sclerosis (MS) may be associated with impairments of neuronal inhibition as part of more general progressive impairments of connectivity. Here, we report results from a prospective, multi-centre fMRI study designed to characterise the changes in patients relative to healthy controls during a simple cued hand movement task. This study was conducted at eight European sites using 1.5 Tesla scanners. Brain deactivation during right hand movement was assessed in 56 right-handed patients with relapsing-remitting or secondary progressive MS without clinically evident hand impairment and in 60 age-matched, healthy subjects. The MS patients showed reduced task-associated deactivation relative to healthy controls in the pre- and postcentral gyri of the ipsilateral hemisphere in the region functionally specialised for hand movement control. We hypothesise that this impairment of deactivation is related to deficits of transcallosal connectivity and GABAergic neurotransmission occurring with the progression of pathology in the MS patients. This study has substantially extended previous observations with a well-powered, multicentre study. The clinical significance of these deactivation changes is still uncertain, but the functional anatomy of the affected region suggests that they could contribute to impairments of motor control.

Keywords

fMRIMultiple sclerosisMovementInhibitory neurotransmission

Abbreviations

EDSS

Extended Disability Status Score

EPI

Echoplanar image

fMRI

Functional MRI

MNI

Montreal Neurological Institute

PMd

Dorsal premotor cortex

ROI

Region of interest

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • S. C. Manson
    • 1
    • 2
  • C. Wegner
    • 1
  • M. Filippi
    • 3
  • F. Barkhof
    • 4
  • C. Beckmann
    • 1
  • O. Ciccarelli
    • 5
  • N. De Stefano
    • 6
  • Christian Enzinger
    • 7
  • F. Fazekas
    • 7
  • F. Agosta
    • 3
  • A. Gass
    • 8
  • J. Hirsch
    • 8
  • H. Johansen-Berg
    • 1
  • L. Kappos
    • 8
  • T. Korteweg
    • 4
  • C. Polman
    • 4
  • L. Mancini
    • 5
    • 9
  • F. Manfredonia
    • 5
  • S. Marino
    • 6
  • D. H. Miller
    • 5
  • X. Montalban
    • 10
  • J. Palace
    • 1
  • M. Rocca
    • 3
  • S. Ropele
    • 7
  • A. Rovira
    • 10
  • S. Smith
    • 1
  • A. Thompson
    • 5
  • J. Thornton
    • 5
  • T. Yousry
    • 5
  • J. A. Frank
    • 2
  • P. M. Matthews
    • 1
    • 11
    • 12
  1. 1.Centre for Functional Magnetic Resonance Imaging of the BrainUniversity of OxfordOxfordUK
  2. 2.Experimental RadiologyNational Institutes of HealthBethesdaUSA
  3. 3.Neuroimaging Research Unit, Department of NeurologyScientific Institute and UniversityMilanItaly
  4. 4.Department of RadiologyVU University Medical CentreAmsterdamThe Netherlands
  5. 5.NMR Research Unit, Institute of NeurologyUniversity College LondonLondonUK
  6. 6.Department of Neurological and Behavioural SciencesUniversity of SienaSienaItaly
  7. 7.Department of NeurologyMedical University GrazGrazAustria
  8. 8.Department of NeurologyUniversity HospitalBaselSwitzerland
  9. 9.Department of Neuroradiology, National Hospital for Neurology and NeurosurgeryUCLH NHS Foundation TrustLondonUK
  10. 10.Department of Radiology, Magnetic Resonance UnitHospital Vall d’HebronBarcelonaSpain
  11. 11.Department of Clinical NeurosciencesImperial CollegeLondonUK
  12. 12.Clinical Imaging Centre, Clinical Pharmacology and Discovery MedicineGlaxoSmithKline, Hammersmith Hospital LondonUK