Differences on Brain Connectivity in Adulthood Are Present in Subjects with Iron Deficiency Anemia in Infancy

Abstract

Iron deficiency continues to be the most prevalent micronutrient deficit worldwide. Since iron is involved in several processes including myelination, dopamine neurotransmission and neuronal metabolism, the presence of iron deficiency anemia (IDA) in infancy relates to long-lasting neurofunctional effects. There is scarce data regarding whether these effects would extend to former iron deficient anemic human adults. Resting state functional magnetic resonance imaging (fMRI) is a novel technique to explore patterns of functional connectivity. Default Mode Network (DMN), one of the resting state networks, is deeply involved in memory, social cognition and self-referential processes. The four core regions consistently identified in the DMN are the medial prefrontal cortex, posterior cingulate/retrosplenial cortex and left and right inferior parietal cortex. Therefore to investigate the DMN in former iron deficient anemic adults is a particularly useful approach to elucidate de long term effects on functional brain. We conducted this research to explore the connection between IDA in infancy and altered patterns of resting state brain functional networks in young adults. Resting-state fMRI studies were performed to 31 participants that belong to a follow-up study since infancy. Of them, 14 participants were former iron deficient anemic in infancy and 17 were controls, with mean age of 21.5 years (±1.5) and 54.8% were males. Resting-state fMRI protocol was used and the data was analyzed using the seed based connectivity statistical analysis to assess the DMN. We found that compared to controls, former iron deficient anemic subjects showed posterior DMN decreased connectivity to the left posterior cingulate cortex (PCC), whereas they exhibited increased anterior DMN connectivity to the right PCC. Differences between groups were also apparent in the left medial frontal gyrus, with former iron deficient anemic participants having increased connectivity with areas included in DMN and dorsal attention networks. These preliminary results suggest different patterns of functional connectivity between former iron deficient anemic and control young adults. Indeed, IDA in infancy, a common nutritional problem among human infants, may turn out to be important for understanding the mechanisms of cognitive alterations, common in adulthood.

Keywords: brain connectivity; default mode network; infancy; iron deficiency anemia; long-lasting effects; resting state networks.

Figure 1

Right posterior cingulate cortex (PCC) connectivity in Controls. Right PCC connectivity greater in Control group. Red indicates regions with significance p < 0.02 and yellow indicates regions with significance p < 0.005.

Figure 2

Right PCC connectivity in former iron-deficiency anemia (FIDA). Right PCC connectivity greater in FIDA group. Red indicates regions with significance p < 0.02 and yellow indicates regions with significance p < 0.005.

Figure 3

Left PCC connectivity in Control group. Red indicates regions with significance p < 0.005.

Figure 4

Left medial frontal gyrus (MFG) connectivity in FIDA group. Red indicates regions with significance p < 0.005.

Figure 5

Mean connectivity matrix. Mean Connectivity matrix in Controls and FIDA groups. Color bar indicates Pearsons r correlation ranging from 1 to −1, hot colors indicating positive correlation between two regions. Vertical and horizontal partitions represent functional connectivity networks.