Abstract
Maturational processes in the developing brain are disrupted by exposure to environmental toxicants, setting the stage for deviant developmental trajectories. Manganese (Mn) is an essential nutrient that is neurotoxic at high levels of exposure, particularly affecting the basal ganglia and prefrontal cortex. Both the intensity and timing of exposure matter; deciduous teeth can be used to retrospectively and objectively determine early-life windows of vulnerability. The aim of this pilot study was to examine associations between prenatal, early postnatal and childhood dentine Mn concentrations and intrinsic functional connectivity (iFC) of adolescents’ brains. 14 adolescents (12–18 years; 6 girls) from northern Italian regions with either current, historic or no Mn contamination, completed a 10-minute resting state functional Magnetic Resonance Imaging (MRI) scan in an 1.5T MRI scanner. We estimated prenatal, early postnatal and childhood Mn concentrations in deciduous teeth using laser ablation-inductively coupled plasma-mass spectrometry. We performed seed-based correlation analyses, focusing on six subcortical seeds (left and right caudate, putamen, pallidum) and one cortical seed (bilateral middle frontal gyrus) from Harvard-Oxford atlases. We examined linear and quadratic correlations between log-transformed Mn concentrations and seed-based iFC (Bonferroni-corrected p<0.0023), controlling for either socio-economic status, sex or age. Dentine Mn concentrations (Mn:Calcium ratio) were highest during the prenatal period (median = 0.48) and significantly declined during the early postnatal (median = 0.14) and childhood periods (median = 0.006). Postnatal Mn concentrations were associated with: 1) increased iFC between the middle frontal gyrus and medial prefrontal cortex; 2) decreased iFC between the right putamen and pre- and postcentral gyrus. Together, these findings suggest that early postnatal Mn concentrations are associated with increased iFC within cognitive control brain areas, but decreased iFC between motor areas in adolescents. Future studies should replicate these findings in larger samples, and link brain connectivity measures to cognitive and motor outcomes.
Highlights
Manganese (Mn) is a prevalent trace metal that is essential for adequate bone growth and enzyme function [1]
Our main findings were that adolescents with higher early postnatal Mn concentrations showed: 1) increased intrinsic functional connectivity between the middle frontal gyrus and medial prefrontal cortex; and 2) decreased connectivity between the right putamen and the pre- and postcentral gyrus
Other studies focusing on brain volume showed that the basal ganglia is affected by early-life Mn exposure [19], and the volume of the prefrontal cortex is reduced in those with higher early-life exposure to other metals as well [50]
Summary
Manganese (Mn) is a prevalent trace metal that is essential for adequate bone growth and enzyme function [1]. Prior studies have shown that early-life Mn concentrations are associated with the function and structure of brain areas implicated in motor and cognitive control, including the basal ganglia and prefrontal cortex. In addition to not measuring fetal and childhood exposure directly [21], these measures do not allow one to investigate vulnerability windows during which exposure is harmful This may lead to missed associations, as it has been shown that associations between early-life Mn concentrations and neurodevelopment in children and adolescents do depend on the intensity and on the timing of exposure [12, 15]. Teeth biomarkers reflect direct fetal exposure, unlike other biomarkers such as maternal blood during pregnancy [21] The aim of this pilot study was to examine how prenatal, early postnatal and childhood dentine Mn concentrations in deciduous teeth are associated with intrinsic functional connectivity. We expected adolescents with higher early-life Mn concentrations to show reduced intrinsic functional connectivity between the basal ganglia and prefrontal cortex [17], reduced connectivity between the prefrontal and parietal cortex, and reduced connectivity between the basal ganglia and motor cortex
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