While fatigue is prevalent in chronic diseases, the neural mechanisms underlying this symptom remain unknown. Magnetic resonance imaging (MRI) has the potential to enable us to characterize this symptom. The aim of this review was to gather and appraise the current literature on MRI studies of fatigue in chronic diseases. We systematically searched the following databases: MedLine, PsycInfo, Embase and Scopus (inception to April 2016). We selected studies according to a predefined inclusion and exclusion criteria. We assessed the quality of the studies and conducted descriptive statistical analyses. We identified 26 studies of varying design and quality. Structural and functional MRI, alongside diffusion tensor imaging (DTI) and functional connectivity (FC) studies, identified significant brain indicators of fatigue. The most common regions were the frontal lobe, parietal lobe, limbic system and basal ganglia. Longitudinal studies offered more precise and reliable analysis. Brain structures found to be related to fatigue were highly heterogeneous, not only between diseases, but also for different studies of the same disease. Given the different designs, methodologies and variable results, we conclude that there are currently no well-defined brain indicators of fatigue in chronic diseases.
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