The purpose of the present study is to examine the effects of mental fatigue and motivation on neural network dynamics activated during task switching. Mental fatigue was induced by 2 h of continuous performance; after which subjects were motivated by using social comparison and monetary reward as motivating factors to perform well for an additional 20 min. EEG coherence was used as a measure of synchronization of brain activity. Electrodes of interest were identified using a data-driven pre-processing method (ten Caat, M., Lorist, M.M., Bezdan, E., Roerdink, J.B.T.M., Maurits, N.M., 2008a. High-density EEG coherence analysis using functional units applied to mental fatigue. J. Neurosci. Meth. 171, 271-278; ten Caat, M., Maurits, N.M. and Roerdink, J.B.T.M., 2008b. Data-driven visualization and group analysis of multichannel EEG coherence with functional units. IEEE T. Vis. Comp. Gr. 14, 756-771). Performance on repetition trials was faster and more accurate than on switch trials. EEG data revealed more pronounced, frequency specific fronto-parietal network activation in switch trials, while power density was higher in repetition trials. The effects of mental fatigue on power and coherence were widespread, and not limited to specific frequency bands. Moreover, these effects were independent of specific task manipulations. This increase in neuronal activity and stronger synchronization between neural networks did not result in more efficient performance; response speed decreased and the number of errors increased in fatigued subjects. A modulation of the dopamine system is proposed as a common mechanism underlying the observed the fatigue effects.