BackgroundMany brain tumor patients suffer from fatigue which severely affects their quality of life. There is a lack of objective measurements for fatigue in brain tumor patients. We aimed to find a neurophysiological correlate for fatigue in brain tumor patients. For this purpose, we correlated brain activity associated with phasic alertness with self-reported ratings of fatigue. MethodsPatients with a meningioma, a low-grade glioma or a high-grade glioma (N = 63) participated in this fMRI study. Brain activity in the central executive network (CEN) and default mode network (DMN) associated with phasic alertness was correlated with self-reported fatigue measured with the multidimensional fatigue inventory (MFI-20). Follow-up analyses were performed for MFI-20 domain scores, individual regions within CEN and DMN, and the tumor sub-groups separately. ResultsMFI-20 scores correlated significantly with DMN activity associated with phasic alertness, but not with CEN activity. These results were consistent for each tumor sub-group. Within the DMN, the correlations were strongest in left and right lingual cortex, left and right cuneus, and right precuneus. DiscussionSelf-reported fatigue in brain tumor patients was associated with objective measurements of brain activity, specifically the DMN activity related to phasic alertness. This association represents an important step in the development of a biomarker for fatigue in brain tumor patients, and possibly for other patients that suffer from fatigue.