Functional activity of the caudate mediates the relation between early childhood microstructural variations and elevated metabolic syndrome scores

•Neuroimaging of the caudate in relation to metabolic syndrome score (MetS).•Microstructure at 4.5 and functional activity at 7.5 years correlated with MetS.•Functional activity fully mediates the link between microstructure and MetS.•Inhibitory control is not a mediator for caudate functional activity and MetS. Metabolic syndrome score in children assesses the risk of developing cardiovascular disease in future. We aim to probe the role of the caudate in relation to the metabolic syndrome score. Furthermore, using both functional and structural neuroimaging, we aim to examine the interplay between functional and structural measures. A longitudinal birth cohort study with functional and structural neuroimaging data obtained at 4.5, 6.0 and 7.5 years and metabolic syndrome scores at 8.0 years was used. Pearson correlation and linear regression was used to test for correlation fractional anisotropy (FA) and fractional amplitude of low frequency fluctuations (fALFF) of the caudate with metabolic syndrome scores. Mediation analysis was used to test if later brain measures mediated the relation between earlier brain measures and metabolic syndrome scores. Inhibitory control was also tested as a mediator of the relation between caudate brain measures and metabolic syndrome scores. FA at 4.5 years and fALFF at 7.5 years of the left caudate was significantly correlated with metabolic syndrome scores. Post-hoc mediation analysis showed that fALFF at 7.5 years fully mediated the relation between FA at 4.5 years and metabolic syndrome scores. Inhibitory control was significantly correlated with fALFF at 7.5 years, but did not mediate the relation between fALFF at 7.5 years and metabolic syndrome scores. We found that variations in caudate microstructure at 4.5 years predict later variation in functional activity at 7.5 years. This later variation in functional activity fully mediates the relation between microstructural changes in early childhood and metabolic syndrome scores at 8.0 years.