White matter damage across frontal–subcortical circuits in carbon monoxide intoxication: Insights from fixel-based analysis

Background Carbon monoxide intoxication (COI) can cause white matter damage through neurotoxic effects. This study investigated these abnormalities within frontal–subcortical circuits and their association with cognitive impairment. Methods 91 COI patients at chronic stage and 20 heathy controls were enrolled. Patients were divided into 3 severity groups (normal cognition; mild cognitive impairment, MCI; and dementia). Voxel-based morphometry and fixel-based analysis were evaluated between patients, as well as across different severity subgroups, and healthy controls. Regression analysis was conducted between the fixel derived metrics and the cognitive composite scores. Significance was set as family-wise error-corrected p < 0.05. Results White matter damage can be detected across frontal–subcortical circuits at chronic stage of CO intoxication. Compared with healthy controls, damage in COI patients with normal cognition can be found in the cingulum even without significant grey matter lesion. The COI-MCI group showed sporadically localized white matter abnormalities in motor, dorsolateral prefrontal and anterior cingulate circuits, whereas the COI-Dementia group demonstrated deficits involving multiple major white matter tracts, including the anterior limb of the internal capsule and anterior thalamic radiation, as well as basal ganglia, temporal and occipital lobes. Reduced fixel derived metrics in periventricular and frontal bundles, including the internal capsule, superior corona radiata and cingulum were highly correlated with cognitive performance in executive function (Pearson's r up to 0.674). Conclusions Damage in the frontal–subcortical circuits can be found in patients with carbon monoxide intoxication, which was correlated to the severity in the affected cognitive domains.