Research Article

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. MansonAffiliated withCentre for Functional Magnetic Resonance Imaging of the Brain, University of OxfordExperimental Radiology, National Institutes of Health
  • , C. WegnerAffiliated withCentre for Functional Magnetic Resonance Imaging of the Brain, University of Oxford
  • , M. FilippiAffiliated withNeuroimaging Research Unit, Department of Neurology, Scientific Institute and University
  • , F. BarkhofAffiliated withDepartment of Radiology, VU University Medical Centre
  • , C. BeckmannAffiliated withCentre for Functional Magnetic Resonance Imaging of the Brain, University of Oxford
  • , O. CiccarelliAffiliated withNMR Research Unit, Institute of Neurology, University College London
  • , N. De StefanoAffiliated withDepartment of Neurological and Behavioural Sciences, University of Siena
  • , Christian EnzingerAffiliated withDepartment of Neurology, Medical University Graz
  • , F. FazekasAffiliated withDepartment of Neurology, Medical University Graz
    • , F. AgostaAffiliated withNeuroimaging Research Unit, Department of Neurology, Scientific Institute and University
    • , A. GassAffiliated withDepartment of Neurology, University Hospital
    • , J. HirschAffiliated withDepartment of Neurology, University Hospital
    • , H. Johansen-BergAffiliated withCentre for Functional Magnetic Resonance Imaging of the Brain, University of Oxford
    • , L. KapposAffiliated withDepartment of Neurology, University Hospital
    • , T. KortewegAffiliated withDepartment of Radiology, VU University Medical Centre
    • , C. PolmanAffiliated withDepartment of Radiology, VU University Medical Centre
    • , L. ManciniAffiliated withNMR Research Unit, Institute of Neurology, University College LondonDepartment of Neuroradiology, National Hospital for Neurology and Neurosurgery, UCLH NHS Foundation Trust
    • , F. ManfredoniaAffiliated withNMR Research Unit, Institute of Neurology, University College London
    • , S. MarinoAffiliated withDepartment of Neurological and Behavioural Sciences, University of Siena
    • , D. H. MillerAffiliated withNMR Research Unit, Institute of Neurology, University College London
    • , X. MontalbanAffiliated withCentre for Functional Magnetic Resonance Imaging of the Brain, University of OxfordDepartment of Radiology, Magnetic Resonance Unit, Hospital Vall d’Hebron
    • , J. PalaceAffiliated withCentre for Functional Magnetic Resonance Imaging of the Brain, University of Oxford
    • , M. RoccaAffiliated withNeuroimaging Research Unit, Department of Neurology, Scientific Institute and University
    • , S. RopeleAffiliated withDepartment of Neurology, Medical University Graz
    • , A. RoviraAffiliated withCentre for Functional Magnetic Resonance Imaging of the Brain, University of OxfordDepartment of Radiology, Magnetic Resonance Unit, Hospital Vall d’Hebron
    • , S. SmithAffiliated withCentre for Functional Magnetic Resonance Imaging of the Brain, University of Oxford
    • , A. ThompsonAffiliated withNMR Research Unit, Institute of Neurology, University College London
    • , J. ThorntonAffiliated withNMR Research Unit, Institute of Neurology, University College London
    • , T. YousryAffiliated withNMR Research Unit, Institute of Neurology, University College London
    • , J. A. FrankAffiliated withExperimental Radiology, National Institutes of Health
    • , P. M. MatthewsAffiliated withCentre for Functional Magnetic Resonance Imaging of the Brain, University of OxfordDepartment of Clinical Neurosciences, Imperial CollegeClinical Imaging Centre, Clinical Pharmacology and Discovery Medicine, GlaxoSmithKline, Hammersmith Hospital Email author 

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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.

Keywords

fMRI Multiple sclerosis Movement Inhibitory neurotransmission