Iron content affects age group differences in associative learning-related fMRI activity
Jessica R Petok1, Jenna L Merenstein2, Ilana J Bennett3
1Department of Psychology, St. Olaf College, United States.
Neuroimage
|November 30, 2023
Summary
Older adults have more brain iron, affecting functional magnetic resonance imaging (fMRI) signals. Accounting for iron reveals age-related brain activity differences missed in previous aging studies.
Area of Science:
- Neuroimaging
- Neuroscience of Aging
- Iron Metabolism in the Brain
Background:
- Iron accumulates differentially in brain regions with age, with higher concentrations in the basal ganglia compared to the hippocampus in older adults.
- Iron's presence can influence neuronal function and alter functional magnetic resonance imaging (fMRI) Blood-Oxygen-Level-Dependent (BOLD) signals.
- Age-related variations in iron content may confound interpretations of fMRI studies in aging populations.
Purpose of the Study:
- To investigate the impact of iron accumulation on age-related differences in task-related brain activity.
- To examine how iron levels modulate fMRI signals in specific brain regions (basal ganglia and hippocampus) during an associative learning task.
- To determine if controlling for iron content refines the understanding of age-group differences in neural activity.
Main Methods:
- Functional magnetic resonance imaging (fMRI) was conducted on 28 younger and 22 older adults performing an associative learning task.
- Iron concentration was quantified using quantitative susceptibility mapping (QSM) and R2* relaxation rates derived from multi-echo gradient echo sequences.
- Learning performance and brain activity were compared between age groups, with and without controlling for estimated iron content.
Main Results:
- Older adults exhibited lower learning performance than younger adults, consistent with prior findings.
- Significant age-group differences in iron content were most pronounced in the basal ganglia (putamen, caudate).
- In the hippocampus and globus pallidus, older adults showed higher learning-related activity than younger adults, irrespective of iron levels. However, in the putamen, younger adults showed higher activity than older adults only after controlling for iron, suggesting iron masked this age-related difference.
Conclusions:
- Age-related iron accumulation influences both neuronal function and fMRI signal measurements in specific basal ganglia nuclei and the hippocampus.
- Failure to account for regional iron variations may lead to underestimation of age-group differences in task-related brain activity in fMRI studies of aging.
- This study highlights the importance of considering iron content for accurate interpretation of neuroimaging findings in aging research.


