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

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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.

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Abbreviations

EDSS:

Extended Disability Status Score

EPI:

Echoplanar image

fMRI:

Functional MRI

MNI:

Montreal Neurological Institute

PMd:

Dorsal premotor cortex

ROI:

Region of interest

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Acknowledgments

PMM thanks the MRC (UK) and the MS Society of Great Britain and Northern Ireland for support. PMM is an employee of GlaxoSmithKline. The design and preparation of this review were done under the auspices of the European Community network for Magnetic Resonance research in MS (MAGNIMS).

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Authors and Affiliations

  1. Centre for Functional Magnetic Resonance Imaging of the Brain, University of Oxford, Oxford, UK

    S. C. Manson, C. Wegner, C. Beckmann, H. Johansen-Berg, J. Palace, S. Smith & P. M. Matthews

  2. Experimental Radiology, National Institutes of Health, Bethesda, USA

    S. C. Manson & J. A. Frank

  3. Neuroimaging Research Unit, Department of Neurology, Scientific Institute and University, Ospedale San Raffaele, Milan, Italy

    M. Filippi, F. Agosta & M. Rocca

  4. Department of Radiology, VU University Medical Centre, Amsterdam, The Netherlands

    F. Barkhof, T. Korteweg & C. Polman

  5. NMR Research Unit, Institute of Neurology, University College London, London, UK

    O. Ciccarelli, L. Mancini, F. Manfredonia, D. H. Miller, A. Thompson, J. Thornton & T. Yousry

  6. Department of Neurological and Behavioural Sciences, University of Siena, Siena, Italy

    N. De Stefano & S. Marino

  7. Department of Neurology, Medical University Graz, Graz, Austria

    Christian Enzinger, F. Fazekas & S. Ropele

  8. Department of Neurology, University Hospital, Kantonsspital, Basel, Switzerland

    A. Gass, J. Hirsch & L. Kappos

  9. Department of Neuroradiology, National Hospital for Neurology and Neurosurgery, UCLH NHS Foundation Trust, London, UK

    L. Mancini

  10. Department of Radiology, Magnetic Resonance Unit, Hospital Vall d’Hebron, Barcelona, Spain

    X. Montalban & A. Rovira

  11. Department of Clinical Neurosciences, Imperial College, London, UK

    P. M. Matthews

  12. Clinical Imaging Centre, Clinical Pharmacology and Discovery Medicine, GlaxoSmithKline, Hammersmith Hospital, London, UK

    P. M. Matthews

Authors
  1. S. C. Manson
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  2. C. Wegner
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  3. M. Filippi
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  4. F. Barkhof
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  5. C. Beckmann
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  10. F. Agosta
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  11. A. Gass
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  12. J. Hirsch
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  13. H. Johansen-Berg
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  14. L. Kappos
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  15. T. Korteweg
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  16. C. Polman
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  17. L. Mancini
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  18. F. Manfredonia
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  19. S. Marino
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  20. D. H. Miller
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  21. X. Montalban
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  22. J. Palace
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  23. M. Rocca
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  24. S. Ropele
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  25. A. Rovira
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  26. S. Smith
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  27. A. Thompson
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  28. J. Thornton
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  29. T. Yousry
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  30. J. A. Frank
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  31. P. M. Matthews
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Corresponding author

Correspondence to P. M. Matthews.

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Manson, S.C., Wegner, C., Filippi, M. et al. Impairment of movement-associated brain deactivation in multiple sclerosis: further evidence for a functional pathology of interhemispheric neuronal inhibition. Exp Brain Res 187, 25–31 (2008). https://doi.org/10.1007/s00221-008-1276-1

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  • DOI: https://doi.org/10.1007/s00221-008-1276-1

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