title: Attention-related changes in short-term cortical plasticity help to explain fatigue in multiple sclerosis.
abstract: 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.
authors.affiliation: IRCCS Neuromed Institute, Pozzilli, ItalyDepartment of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Conte
authors.affiliation: IRCCS Neuromed Institute, Pozzilli, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Li Voti
authors.affiliation: IRCCS Neuromed Institute, Pozzilli, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Pontecorvo
authors.affiliation: Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy.
authors.forename: Maria Esmeralda
authors.initials: ME
authors.lastname: Quartuccio
authors.affiliation: Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy.
authors.forename: Viola
authors.initials: V
authors.lastname: Baione
authors.affiliation: Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Rocchi
authors.affiliation: Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Cortese
authors.affiliation: IRCCS Neuromed Institute, Pozzilli, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Bologna
authors.affiliation: Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy.
authors.forename: Ada
authors.initials: A
authors.lastname: Francia
authors.affiliation: IRCCS Neuromed Institute, Pozzilli, ItalyDepartment of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy alfredo.berardelli@uniroma1.it.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Berardelli
mesh_terms: D000328:Adult; D001288:Attention; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000503:physiopathology; D019054:Evoked Potentials, Motor / Q000502:physiology*; D005221:Fatigue / Q000503:physiopathology*; D005260:Female; D006225:Hand; D006801:Humans; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000503:physiopathology*; D009103:Multiple Sclerosis / Q000503:physiopathology*; D009473:Neuronal Plasticity; D050781:Transcranial Magnetic Stimulation
keywords: 5-Hz rTMS; Multiple sclerosis; attention; cortical plasticity; fatigue; paired associative stimulation