Exposure to lead, mercury, and polychlorinated biphenyls (PCBs) has been causally linked to spatial memory deficits and hippocampal changes in animal models. The Inuit community in Northern Canada is exposed to higher concentrations of these contaminants compared to the general population. This study aimed to 1) investigate associations between prenatal and current contaminant exposures and medial temporal brain volumes in Inuit late adolescents
2) examine the relationship between these brain structures and spatial memory
and 3) assess the mediating role of brain structures in the association between contaminant exposure and spatial memory. Prenatal and current exposures were assessed from blood samples collected at birth and at the time of testing in 71 participants aged 16-22. Volumetric measurements of the hippocampi, entorhinal, and parahippocampal cortices from T1-weighted images were obtained using the Automatic Segmentation of Hippocampal Subfields method. Spatial navigation memory was evaluated using a computerized Morris Water Maze task. Prenatal lead exposure was associated with a smaller left hippocampal volume (β = -0.30, 95% CI = -0.56, -0.05), while current mercury (β = -0.34, 95% CI = -0.62, -0.06) and PCB-153 (β = -0.36, 95% CI = -0.70, -0.01) exposures were linked to a smaller left entorhinal cortex. The volume of the left entorhinal cortex positively correlated with spatial navigation memory performance (β = 0.26, 95% CI = 0.01, 0.51). These findings suggest specific windows of brain vulnerability to these contaminants, with the entorhinal cortex playing a key role in spatial navigation memory and potentially mediating the effects of exposure.