The association between post-stroke fatigue and neuroimaging markers: a scoping review

Post-stroke fatigue (PSF) is a highly prevalent and disabling symptom that significantly impairs quality of life and rehabilitation outcomes after stroke. Despite its clinical importance, the neural mechanisms underlying PSF remain poorly understood. Neuroimaging provides a means to identify structural and functional brain markers associated with PSF; however, existing findings are heterogeneous and inconclusive. Further, the role of individual characteristics in the PSF-neuroimaging marker association has not been systematically examined. This scoping review aimed to identify neuroimaging markers associated with PSF and to explore whether individual characteristics, including age, sex, stroke severity, and fatigue severity, account for the inconsistency in these associations across studies. Five electronic databases (Medline, CINAHL, EMBASE, PubMed, and PsycInfo) were searched from January 1980 to May 2025. Studies were included if they assessed adult-onset stroke, measured fatigue using any validated or non-validated tool, and examined associations between fatigue and neuroimaging markers using MRI, CT, DTI, PET, or functional MRI. Two reviewers independently screened and extracted data. Findings were mapped descriptively across imaging markers, and exploratory comparisons were conducted to examine whether demographic factors and symptom severity differ among studies. Thirty studies including 3,660 participants were included. Functional connectivity was the most consistently associated neuroimaging marker, with 67% of studies reporting significant associations between altered resting-state connectivity and PSF. Lesion location was associated with PSF in 45% of studies, particularly involving subcortical regions such as the basal ganglia, thalamus, and brainstem. Structural connectivity and brain atrophy were understudied, while lesion size, lesion laterality, number of lesions, and white matter lesions were generally not associated with PSF. Exploratory analyses suggested that older mean age, a lower proportion of females, and higher fatigue prevalence were associated with studies reporting significant relationship between neuroimaging markers and PSF. This scoping review suggests that altered functional connectivity and lesion location, particularly involving the fronto-striato-thalamic circuitry, are promising neuroimaging markers of PSF. The findings further indicate that demographic factors and symptom severity may account for the inconsistency in neuroimaging literature. Future studies should incorporate network-based imaging approaches, assess distinct domains of fatigue, and account for individual characteristics to better delineate the neural mechanisms of PSF and support personalized rehabilitation strategies.