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Patterns of subcortical tissue iron levels across the lifespan measured with functional MRI

Mertens, A. T.; Pavelka, D. J.; Foley, L.; Myers, K.; Goldsmith, C.; Wolfe, T.; Oleson, J. J.; Doucet, G. E.

2026-09-15 neuroscience
10.64898/2026.09.09.750391 bioRxiv
Show abstract

Iron is essential for neurophysiological health. Prior work has shown that subcortical tissue iron levels are the highest among all brain regions but also change over the lifespan. Recent functional MRI (fMRI) studies have provided evidence that an fMRI-derived iron-sensitive signal may index relative iron concentration in subcortical regions. In this context, we aimed to characterize the lifespan trajectory of this fMRI-derived iron-sensitive signal (relative iron quantification) in 10 subcortical regions and 14 thalamic nuclei from 881 healthy participants aged 12 to 88 years, using resting-state fMRI. Regressions were run with age as a predictor, separately for males (N = 429) and females (N = 452). The main results show non-linear effects of age, with an overall increase in iron levels across most subcortical regions within each sex. Six of the 14 thalamic nuclei in male participants had similar slopes of their lifespan iron levels, showing some homogeneity. The thalamic nuclei of female participants showed less agreement in slopes. This study provides new insight into the typical trajectory of iron levels across all major subcortical regions throughout the lifespan.

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