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

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

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.

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.

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.

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.