Cognitive control inhibition networks in adulthood are impaired by early iron deficiency in infancy

Abstract

Iron deficiency, a common form of micronutrient deficiency, primarily affects children and women. The principal cause of iron deficiency is undernutrition in low-income countries and malnutrition in middle to upper income regions. Iron is a key element for myelin production, neuronal metabolism, and dopamine functions. Iron deficiency in early life can alter brain development and exert long-lasting effects. Control inhibition is an executive function that involves several brain regions, including the prefrontal cortex and caudate and sub-thalamic nuclei. Dopamine is the prevalent neurotransmitter underlying cognitive inhibition. We followed cohort study participants who had iron deficiency anemia in infancy as well non-anemic controls. At 22 years of age, the participants were subjected to functional magnetic resonance imaging (fMRI) to evaluate the correlation between functional connectivity and performance on an inhibitory cognitive task (Go/No-Go). We hypothesized that former iron deficient anemic (FIDA) participants demonstrate less strength in functional connectivity compared with controls (C). There were not significant group differences in the behavioral results in terms of accuracy and response time. A continuous covariate interaction analysis of functional connectivity and the Go/No-Go scores demonstrated significant differences between the FIDA and C groups. The FIDA participants demonstrated less strength in connectivity in brain regions related to control inhibition, including the medial temporal lobe, impairment in the integration of the default mode network (indicating decreased attention and alertness), and an increase in connectivity in posterior brain areas, all of which suggest slower circuitry maturation. The results support the hypothesis that FIDA young adults show differences in the connectivity of networks related to executive functions. These differences could increase their vulnerability to develop cognitive dysfunctions or mental disorders in adulthood.

Keywords

• Iron deficiency anemia in infancy
• Early adulthood
• Cognitive inhibition
• rs-fMRI