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Neural Plasticity
Volume 2015, Article ID 616242, 9 pages
Clinical Study

Neurophysiological Correlates of Central Fatigue in Healthy Subjects and Multiple Sclerosis Patients before and after Treatment with Amantadine

1Department of Medicine, Surgery and Neuroscience, Neurology and Clinical Neurophysiology Section, Brain Investigation & Neuromodulation Lab. (Si-BIN Lab), University of Siena, 53100 Siena, Italy
2Berenson-Allen Center for Noninvasive Brain Stimulation, Beth Israel Medical Center, Harvard Medical School, Boston, MA 02215, USA
3Unit of Neurology, Azienda Sanitaria di Firenze, 50121 Florence, Italy

Received 1 March 2015; Accepted 17 June 2015

Academic Editor: Preston E. Garraghty

Copyright © 2015 Emiliano Santarnecchi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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 -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.