Dysfunctional connectivity within hippocampal and entorhinal networks underlies early-life iron deficiency induced...

Early-life iron deficiency (EID) has an adverse effect on cognition. Previous MRI studies revealed that EID could produce brain structural changes, while the significance remains elusive. To elucidate correlative functional changes is thus important. A low-iron diet feeding protocol was used to produce EID in rats, and a three-chamber test was used to evaluate social recognitions. T2-weighted and functional MRI (fMRI) were employed to conduct voxel-based morphometry (VBM) and voxel-wise functional connectivity (FC) analyses. Seed-based FC analyses were conducted, and based on the results, the hippocampus and entorhinal cortex (EC) were further respectively subdivided into 8 and 5 subregions, in order to perform deep seed-based FC analyses. EID rats were significantly impaired in social recognition. VBM analyses showed enlarged hippocampus and EC, and the FC between them was significantly decreased. Our deep seed-based analyses of FC further identified the impaired networks (p < 0.001, q < 0.05) between these two brain regions and between each of them and a number of other brain networks individually. All these results, although preliminarily, for the first time revealed the dysfunctional connectivity in three networks within the hippocampus and EC of the brain of EID rats, and may have a translational significance in early-diagnosis of EID.