AbstractHuman learning is an active and complex process. However, the brain mechanisms underlying human skill learning and the effect of learning on the communication between brain regions, at different frequency bands, are still largely unknown. Here, we tracked changes in large-scale electrophysiological networks over a 6-week training period during which participants practiced a series of motor sequences during 30 home training sessions. Our findings showed that brain networks become more flexible with learning in all the frequency bands from theta to gamma ranges. We found consistent increase of flexibility in the prefrontal and limbic areas in the theta and alpha band, and over somatomotor and visual areas in the alpha band. Specific to the beta rhythm, we revealed that higher flexibility of prefrontal regions during the early stage of learning strongly correlated with better performance measured during home training sessions. Our findings provide novel evidence that prolonged motor skill practice results in higher, frequency-specific, temporal variability in brain network structure.