Attention-related changes in short-term cortical plasticity help to explain fatigue in multiple sclerosis

Mult Scler. 2016 Sep;22(10):1359-66. doi: 10.1177/1352458515619780. Epub 2015 Dec 16.

Abstract

Background: In multiple sclerosis (MS), pathophysiology of fatigue is only partially known.

Objective: The aim of this study was to investigate whether the attention-induced modulation on short- and long-term cortical plasticity mechanisms in primary motor area (M1) is abnormal in patients with MS-related fatigue.

Methods: All participants underwent 5-Hz repetitive transcranial magnetic stimulation (rTMS), reflecting short-term plasticity, and paired associative stimulation (PAS), reflecting long-term plasticity, and were asked to focus their attention on the hand contralateral to the M1 stimulated. A group of age-matched healthy subjects acted as control.

Results: In patients with MS, 5-Hz rTMS and PAS failed to induce the normal increase in motor-evoked potential (MEP). During the attention-demanding condition, 5-Hz rTMS- and PAS-induced responses differed in patients with MS with and without fatigue. Whereas in patients with fatigue neither technique induced the attention-induced MEP increase, in patients without fatigue they both increased the MEP response, although they did so less efficiently than in healthy subjects. Attention-induced changes in short-term cortical plasticity inversely correlated with fatigue severity.

Conclusion: Short-term and long-term plasticity mechanisms are abnormal in MS possibly owing to widespread changes in ion-channel expression. Fatigue in MS reflects disrupted cortical attentional networks related to movement control.

Keywords: 5-Hz rTMS; Multiple sclerosis; attention; cortical plasticity; fatigue; paired associative stimulation.

MeSH terms

  • Adult
  • Attention*
  • Case-Control Studies
  • Cerebral Cortex / physiopathology
  • Evoked Potentials, Motor / physiology*
  • Fatigue / physiopathology*
  • Female
  • Hand
  • Humans
  • Male
  • Middle Aged
  • Motor Cortex / physiopathology*
  • Multiple Sclerosis / physiopathology*
  • Neuronal Plasticity*
  • Transcranial Magnetic Stimulation