Substantia nigra iron affects functional connectivity networks modifying working memory performance in younger adults

Abstract Brain iron affects working memory (WM) but the impact of iron content in deep grey matter nuclei on WM networks is unknown. We aimed to test whether deep grey matter nuclei iron concentration can affect resting‐state functional connectivity (rsFC) within brain networks modifying WM performance. An N‐back WM paradigm was applied in a hundred healthy younger adults. The participants then underwent a resting‐state functional magnetic resonance imaging (fMRI) for brain network analysis and quantitative susceptibility mapping (QSM) imaging for assessment of deep grey matter nuclei iron concentration. Higher substantia nigra (SN) iron concentration was associated with lower rsFC between SN and brain regions of the temporal/frontal lobe but with better WM performance after controlling for age, gender and education. A follow‐up mediation analysis also indicated that functional connectivity may mediate the link between SN iron and WM performance. Our results suggest that high SN iron concentration may affect communication between the SN and temporal/frontal lobe and is associated with strengthened WM performance in younger adults.