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Altered cerebellar functional connectivity mediates potential adaptive plasticity in patients with multiple sclerosis
  1. S Saini1,
  2. N DeStefano2,
  3. S Smith1,
  4. L Guidi3,
  5. M P Amato4,
  6. A Federico2,
  7. P M Matthews1
  1. 1Centre for Functional Magnetic Resonance Imaging of the Brain, John Radcliffe Hospital, University of Oxford, Oxford, UK
  2. 2Department of Neurology and Behavioural Sciences, University of Siena, Siena, Italy
  3. 3Unit of Neurology, Empoli Hospital, Empoli, Italy
  4. 4Department of Neurology, University of Florence, Florence, Italy
  1. Correspondence to:
 Professor P M Matthews
 Centre for Functional Magnetic Resonance Imaging of the Brain, John Radcliffe Hospital, Headley Way, Headington, Oxford OX3 9DU, UK; paulfmrib.ox.ac.uk

Abstract

Background: The cerebellum is of potential interest for understanding adaptive responses in motor control in patients with multiple sclerosis because of the high intrinsic synaptic plasticity of this brain region.

Objective: To assess the relative roles of interactions between the neocortex and the cerebellum using measures of functional connectivity.

Methods: A role for altered neocortical–cerebellar functional connectivity in adaptive responses to injury from multiple sclerosis was tested using 1.5 T functional magnetic resonance imaging (fMRI) during figure writing with the dominant right hand in patients with predominantly early relapsing-remitting multiple sclerosis.

Results: Patients (n = 14) showed a more bihemispheric pattern of activation in motor cortex than healthy controls (n = 11). Correlations between task related signal changes in neocortical and cerebellar regions of interest were used as a measure of functional connectivity. Healthy controls showed strong functional connectivity between the left motor cortex and the right cerebellar dentate nucleus. Significant connectivity between the left primary motor cortex and the right dentate was not found in patients. However, patients had significant connectivity between the left premotor neocortex and the ipsilateral (left) cerebellar cortex (crus I), which was not found in healthy controls.

Conclusions: Changes in apparent cerebellar–neocortical functional connectivity may mediate potentially adaptive changes in brain motor control in patients with multiple sclerosis. Similar changes in the cerebellum and premotor cortex have been reported in the healthy brain during motor learning, suggesting that common mechanisms may contribute to normal motor learning and motor recovery after injury from multiple sclerosis.

  • multiple sclerosis
  • cerebellum
  • brain repair
  • neurorehabilitation
  • EDSS, expanded disability status score
  • FILM, FMRIB’s improved linear model
  • FLAME, FMRIB’s local analysis of mixed effects
  • FMRIB, Oxford Centre for Functional Magnetic Resonance Imaging of the Brain
  • LI, lateralisation index
  • MCFLIRT, motion correction using FMIRB’s linear image registration tool
  • ROI, region of interest

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Footnotes

  • Competing interests: none declared