Altered central nervous system signal during motor performance in chronic fatigue syndrome
Introduction
The syndrome of chronic fatigue has been described by various terms in the medical literature since the early 17th century. In 1988, the US Centers for Disease Control and Prevention (CDC) proposed a research case definition for chronic fatigue syndrome (CFS) as an illness characterized by an abrupt onset of persistent or relapsing fatigue and other criteria (Holmes et al., 1988). The fatigue in CFS patients is usually described as debilitating or a state of easy fatigability that does not resolve with bed rest, is severe enough to impair average daily activity below 50% of the premorbid level, and lasts for a period of at least 6 months (Gonzalez et al., 1996, Johnson et al., 1999). The fatigue worsens when patients engage in physical activities or muscle exertions (Fukuda et al., 1994, Gonzalez et al., 1996, Johnson et al., 1999). The diagnosis of CFS is difficult to make because of the absence of specific biomedical markers. Thus, the diagnosis depends primarily on determining whether subjective information provided by the patient meets the clinical case definition of the syndrome (Dickinson, 1997, Fukuda et al., 1994, Holmes et al., 1988, Schluederberg et al., 1992).
Several hypotheses have been proposed to outline the etiology and pathology of CFS. One hypothesis is that CFS is a primary affective spectrum disorder, in particular a type of chronic depression (Demitrack, 1994). Others (Zubieta et al., 1994) have suggested that CFS is a persistent immune dysfunction initiated by some infectious process, such as a virus. Demitrack (1994) also proposed that the biological as well as behavioral features of CFS might be linked to endocrine dysfunction of the hypothalamo-pituitary-adrenal axis. In recent years, increasing scientific evidence has emerged to suggest that CFS is a biological illness involving pathology of the central nervous system (Komaroff, 2000).
A number of studies have shown that the central nervous system in CFS patients is affected by the disorder. Kent-Braun et al. (1993) reported that CFS patients have less ability to maximally activate their lower leg muscles, indicating a reduced capacity of brain signal to the working muscle. Post-exercise motor cortical excitability is reduced in CFS patients as compared with healthy volunteers (Samii et al., 1996). Using single photon emission computer tomography (SPECT), researchers found CFS-related perfusion defects in the frontal and temporal lobes (Schwartz et al., 1994a) and impaired cerebral blood flow (Ichise et al., 1992). Magnetic resonance imaging data acquired from CFS patients have shown abnormalities in the white matter signal intensity (Buchwald et al., 1992, Natelson et al., 1993, Schwartz et al., 1994b). Reaction time was slower and amplitude of EEG-derived premovement-related cortical potential reduced in CFS (Gordon et al., 1999). These observations suggest that the central nervous system of CFS patients is altered from the normal state and that the abnormality may be more specific and easier to classify during motor activities that exaggerate the sense of fatigue. However, brain signal changes during muscle exercises that lead to moderate and severe muscle fatigue in CFS have seldom been investigated. None of the previous studies was able to examine motor output, muscle activation, fatigability, and brain signals simultaneously. Recent studies from our laboratory have reported brain activation modulation during low- and high-level motor activity-induced muscle fatigue in healthy volunteers using EEG and functional MRI measurements (Lewandowski et al., 2002, Liu et al., 2002, Liu et al., 2003, Yao et al., 2002). The purpose of this study was to characterize EEG-recorded brain signals in CFS patients and healthy controls during handgrip exercises involving moderate to relatively high levels of muscle fatigue by simultaneously recording scalp EEG, surface EMG, and mechanical output (force) signals. It was hypothesized that brain signals, whether in the time or frequency domain, or both, of CFS patients would differ from those of healthy controls, and the differences may serve as biological markers for more objective diagnosis of CFS.
Section snippets
Subjects
Eight medication-free CFS patients (5 men and 3 women, age=43.1±7.6 years) who met the CDC's criteria for CFS (Holmes et al., 1988) were recruited from the Department of Rheumatic and Immunologic Disease at the Cleveland Clinic. (The patients were medication free on and at least 10 days prior to the experiment day.) All patients were free of neuromuscular and active mood disorders. They were given a detailed history review and physical examination and were screened for active and past
Force
MVC force. The MVC handgrip force (MVC1) of the CFS group (305.8±150.4 N) was significantly lower (P<0.02) than the MVC force of the control group (412.0±103.6 N). At the completion of the experiment (the end of the FT task), the MVC force (MVC2) reduced to 252.6±136.4 N (83% of the MVC1 value) for the CFS group and to 374.6±96.4 N (91% of the MVC1 value) for the control group (Fig. 2A). The decline in the MVC force was significant for the CFS patients (P<0.05), but insignificant for the
Conclusions
This study systematically examined EEG-measured brain signals during non-fatigue and fatigue voluntary motor tasks, and other activities in CFS patients and healthy volunteers. The results suggest that CFS patients are weaker and more easily fatigued than healthy individuals are. The relative power of the EEG theta band frequency in the CFS group is significantly greater after a moderate level of muscle exercise than that in the control group. A significantly higher level of cortical activation
Acknowledgements
This research was partially sponsored by a grant from the Cleveland Clinic (RPC-6345) to VS, by an NIH grant (NS-37400) and a Department of Defense grant (DAMD17-01-1-0665) to GHY, and by departmental research funds of Physical Medicine and Rehabilitation, and the Risman R&D Fund at the Cleveland Clinic Foundation.
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