Fatigue is a common experience that reduces productivity and increases chance of injury, and has been reported as one of most common symptoms with greatest impact on quality-of-life parameters in cancer patients. Neural mechanisms behind fatigue and cancer related fatigue (CRF) are not well known. Recent research has shown dissociation between changes in brain and muscle signals during voluntary muscle fatigue, which may suggest weakening of functional corticomuscular coupling (fCMC). However, this weakening of brain-muscle coupling has never been directly evaluated. More important information could be gained if fCMC is directly detected during fatigue because a voluntary muscle contraction depends on integration of the entire chain of events and is a complex interaction of different components from the central nervous system to peripheral systems. This research, first, evaluated the effect of muscle fatigue on fCMC in healthy people by determining electroencephalography (EEG)-electromyography (EMG) coherence during two stages of a sustained voluntary muscle contraction, one with minimal fatigue and the other with severer fatigue. The obtained results suggest that despite an elevation of the power for both the EEG and EMG activities with muscle fatigue, the fatigue weakens strength of fCMC between the two signals. Secondly, given the fact that there is larger discrepancy between central and peripheral fatigue in CRF, the effect of cancer related fatigue on fCMC was evaluated by comparing EEG-EMG coherence during a muscle fatigue task in CRF patients with healthy controls. CRF patients showed significantly lower fCMC compared to healthy controls during minimal fatigue stage which may be caused by possible pathophysiological impairments in the patients. Finally, to better understand dynamic fatigue effect on fCMC, a single trial coherence estimation based on Morlet wavelet was developed and applied to investigate fatigue effect on fCMC in single trial during repetitive maximal muscle contractions. It was revealed that the decreasing pattern of the fCMC varied among the subjects but the overall decreasing trend was consistent across subjects. The results from the single-trial study suggest it is possible to detect more dynamic fCMC adaptations under acute neuromuscular instability conditions, such as muscle fatigue.;This research reveals that muscle fatigue impairs normal coupling between the central and peripheral neuromuscular systems, which could be a major factor contributing to worsened performance under fatigue influence. In general, cancer patients with fatigue symptom exhibit substantially weakened fCMC, even without influence of muscle fatigue. The findings are potentially important in understanding neural mechanisms of muscle fatigue and cancer related fatigue, and in guiding development of new methodologies to improve diagnosis and treatment of fatigue symptoms in clinical populations.
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