Fatigue caused by sustaining submaximal-intensity muscle contraction(s) involves increased activation in the brain such as primary motor cortex (M1), primary sensory cortex (S1), premotor and supplementary motor area (PM&SMA) and prefrontal cortex (PFC). The synchronized increases in activation level in these cortical areas suggest fatigue-related strengthening of functional coupling within the motor control network. In the present study, this hypothesis was tested using the cross-correlation based functional connectivity (FC) analysis method. Ten subjects performed a 20-minute intermittent (3.5s ON/6.5s OFF, 120 trials total) handgrip task using the right hand at 50% maximal voluntary contraction (MVC) force level while their brain was scanned by a 3 T Siemens Trio scanner using echo planar imaging (EPI) sequence. A representative signal time course of the left M1 was extracted by averaging the time course data of a 2-mm cluster of neighboring voxels of local maximal activation foci, which was identified by a general linear model. Two FC activation maps were created for each subject by cross-correlating the time course data of the minimal (the first 10 trials) and significant (the last 10 trials) fatigue stages across all the voxels in the brain to the corresponding representative time course. Histogram and quantile regression analysis were used to compare the FC between the minimal and significant fatigue stages and the results showed a significant increase in FC among multiple cortical regions, including right M1 and bilateral PM&SMA, S1 and PFC. This strengthened FC indicates that when muscle fatigue worsens, many brain regions increase their coupling with the left M1, the primary motor output control center for the right handgrip, to compensate for diminished force generating capability of the muscle in a coordinated fashion by enhancing the descending command for greater muscle recruitment to maintain the same force.
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