Diminished central activation during maximal voluntary contraction in chronic fatigue syndrome M.L. Schillings a , J.S. Kalkman b,c , S.P. van der Werf c , B.G.M. van Engelen d , G. Bleijenberg b , M.J. Zwarts a,d, * a Department of Clinical Neurophysiology, University Medical Centre Nijmegen, Internal postal code 314, P.O. Box 9101, 6500 HB Nijmegen, Netherlands b Expert Centre Chronic Fatigue, University Medical Centre Nijmegen, Internal postal code 627, P.O. Box 9101, 6500 HB Nijmegen, Netherlands c Department of Medical Psychology, University Medical Centre Nijmegen, Internal postal code 118, P.O. Box 9101, 6500 HB Nijmegen, Netherlands d Department of Neurology, Neuromuscular Centre Nijmegen, University Medical Centre Nijmegen, Internal postal code 326, P.O. Box 9101, 6500 HB Nijmegen, Netherlands Accepted 7 June 2004 Available online 10 July 2004 Abstract Objective: We have investigated whether central activation failure (CAF) is increased during local muscle fatigue in chronic fatigue syndrome (CFS). Methods: Fourteen female CFS patients and 14 age-matched healthy female controls made a 2 min sustained maximal voluntary contraction (MVC) of the biceps brachii muscle. Before, during, and after sustained MVC, electrical endplate stimulation was applied. Force and 5 channel surface EMG (sEMG) were registered. Results: Although force responses upon stimulation during rest did not differ between patients and controls, MVC was significantly lower in patients. Already at the beginning of sustained MVC, CFS patients showed significantly larger CAF than controls (36.5 ^ 17.0% and 12.9 ^ 13.3%, respectively). For all individual patients mean CAF over the first 45 s was higher than 30%, while it was below 30% for all controls. Less peripheral fatigue in patients was demonstrated by the changes in muscle fibre conduction velocity and the differences between force responses before and after contraction. Conclusions: Central activation is diminished in CFS patients. Possible causes include changed perception, impaired concentration, reduced effort and physiologically defined changes, e.g. in the corticospinal excitability or the concentration of neurotransmitters. As a consequence, demands on the muscle are lower, resulting in less peripheral fatigue. Significance: CFS patients show reduced central activation during MVC. The underlying pathophysiological processes remain still to be determined. q 2004 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. Keywords: Chronic fatigue syndrome; Central activation; Sustained maximal voluntary contraction 1. Introduction Chronic fatigue syndrome (CFS) is defined by severe fatigue of at least 6 months duration that interferes substantially with occupational, educational, social, or personal activities, is not alleviated by rest, and is accompanied by at least 4 of 8 specific symptoms (unrefreshing sleep, sore throat, tender lymph nodes, muscle pain, joint pain, impaired memory or concentration, headache, severe post-exertional fatigue; Fukuda et al., 1994). Although much research has been done, physiologi- cal processes playing a role in this disease remain uncertain. Kent-Braun et al. (1993) described that patients suffering from CFS develop relatively large central fatigue during a 4 min sustained maximal contraction of the tibialis anterior muscle. They found a significantly diminished central activation at the end of sustained contraction. Interestingly, they showed that already at the start of exercise in CFS patients force could be added to maximal voluntary contraction (MVC) by superimposed electrical stimulation, indicating that central activation was submaximal. This was Clinical Neurophysiology 115 (2004) 2518–2524 www.elsevier.com/locate/clinph 1388-2457/$30.00 q 2004 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.clinph.2004.06.007 * Corresponding author. Address: Department of Clinical Neurophysiology, University Medical Centre Nijmegen, Internal postal code 314, P.O. Box 9101, 6500 HB Nijmegen, Netherlands. Tel.: þ 31-24- 361-3973; fax: þ 31-24-361-5097. E-mail address: m.zwarts@neuro.umcn.nl (M.J. Zwarts).