title: Neurophysiological Correlates of Central Fatigue in Healthy Subjects and Multiple Sclerosis Patients before and after Treatment with Amantadine.
abstract: In ten healthy subjects and in ten patients suffering from Multiple Sclerosis (MS), we investigated the cortical functional changes induced by a standard fatiguing repetitive tapping task. The Cortical Silent Period (CSP), an intracortical, mainly GABAB-mediated inhibitory phenomenon, was recorded by two different hand muscles, one acting as prime mover of the fatiguing index-thumb tapping task (First Dorsal Interosseous, FDI) and the other one not involved in the task but sharing largely overlapping central, spinal, and peripheral innervation (Abductor Digiti Minimi, ADM). At baseline, the CSP was shorter in patients than in controls. As fatigue developed, CSP changes involved both the "fatigued" FDI and the "unfatigued" ADM muscles, suggesting a cortical spread of central fatigue mechanisms. Chronic therapy with amantadine annulled differences in CSP duration between controls and patients, possibly through restoration of more physiological levels of intracortical inhibition in the motor cortex. These inhibitory changes correlated with the improvement of fatigue scales. The CSP may represent a suitable marker of neurophysiological mechanisms accounting for central fatigue generation either in controls or in MS patients, involving corticospinal neural pools supplying not only the fatigued muscle but also adjacent muscles sharing an overlapping cortical representation.
authors.affiliation: Department of Medicine, Surgery and Neuroscience, Neurology and Clinical Neurophysiology Section, Brain Investigation & Neuromodulation Lab. (Si-BIN Lab), University of Siena, 53100 Siena, Italy ; Berenson-Allen Center for Noninvasive Brain Stimulation, Beth Israel Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Emiliano
authors.initials: E
authors.lastname: Santarnecchi
authors.affiliation: Department of Medicine, Surgery and Neuroscience, Neurology and Clinical Neurophysiology Section, Brain Investigation & Neuromodulation Lab. (Si-BIN Lab), University of Siena, 53100 Siena, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Rossi
authors.affiliation: Department of Medicine, Surgery and Neuroscience, Neurology and Clinical Neurophysiology Section, Brain Investigation & Neuromodulation Lab. (Si-BIN Lab), University of Siena, 53100 Siena, Italy.
authors.forename: Sabina
authors.initials: S
authors.lastname: Bartalini
authors.affiliation: Unit of Neurology, Azienda Sanitaria di Firenze, 50121 Florence, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Cincotta
authors.affiliation: Unit of Neurology, Azienda Sanitaria di Firenze, 50121 Florence, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Giovannelli
authors.affiliation: Department of Medicine, Surgery and Neuroscience, Neurology and Clinical Neurophysiology Section, Brain Investigation & Neuromodulation Lab. (Si-BIN Lab), University of Siena, 53100 Siena, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Tatti
authors.affiliation: Department of Medicine, Surgery and Neuroscience, Neurology and Clinical Neurophysiology Section, Brain Investigation & Neuromodulation Lab. (Si-BIN Lab), University of Siena, 53100 Siena, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Ulivelli
mesh_terms: D000328:Adult; D000547:Amantadine / Q000008:administration & dosage* / Q000627:therapeutic use; D019054:Evoked Potentials, Motor / Q000187:drug effects; D005221:Fatigue / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D005260:Female; D005385:Fingers; D006801:Humans; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000187:drug effects* / Q000503:physiopathology*; D009103:Multiple Sclerosis / Q000150:complications*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000503:physiopathology; D050781:Transcranial Magnetic Stimulation; D055815:Young Adult
chemical_list: D000547:Amantadine