Mental fatigue arises during prolonged cognitively-taxing tasks, leading to performance decrements or time-on-task effects (ToT) and declines through rest or incentives. Although mental fatigue is ubiquitously experienced in daily life and its adverse consequences are documented in a variety of settings, its neurocognitive correlates remain uncertain. This study used the prolonged version of the psychomotor vigilance task (PVT) to induce fatigue and resting-state functional MRI (rs-fMRI) to investigate functional connectivity (FC) correlates of the ToT effect and the motivation effect (monetarily rewarding participants after fatigue induction) in 74 young healthy adults. Fatigue scores (change in mean reaction times between the blocks of PVT) were extracted as a measure of overall performance. Fatigue-resistant (n=25) and fatigue-sensitive (n=24) subjects were separated based on fatigue scores. A data-driven, multi-variate pattern analysis (MVPA) was used to derive suitable seeds (4) for later seed-to-voxel analysis -post hoc analysis- to analyse FC patterns. Behaviourally, subjects showed strong ToT drops in performance, as assessed by increasing reaction times as the test progressed. Extra monetary reward positively affected PVT performance in fatigued subjects. Our rs-fMRI results showed changes in FC in task-related brain regions and non-related regions. Specifically, we found TOT-related connectivity changes between the first two seed regions and areas in the frontal, parietal and temporal regions indicative of sensorimotor and cognitive systems, as well as in the insula and anterior cingulate cortex. Increased connectivity between our first seed and the dorsolateral prefrontal cortex was positively correlated with performance improvement due to the reward effect.