Structural neuroimaging of the planning network in Inuit adolescents prenatally exposed to lead

Exposure to lead has been linked to alterations in cortical organization and impaired executive function. However, neural correlates of the association between lead exposure and cognitive planning remain poorly characterized. This study investigated whether brain structures mediate the association between prenatal lead exposure and planning performance in late adolescence. Seventy-two Inuit participants (mean age = 18.4 years, range = 16.25-21.55 years) from Nunavik, Canada, completed the Tower of London planning task as well as a T1-weighted brain magnetic resonance imaging (MRI) scan to measure cortical thickness and surface area of key brain regions of the planning network. Prenatal exposure was estimated by measuring lead concentrations in cord blood samples at birth. Structural equation models tested the mediating role of regional brain structure in the association between prenatal lead exposure and cognitive planning, adjusting for sociodemographic characteristics and fish nutrients. Results showed that higher cord blood lead concentrations were associated with reduced cortical thickness in multiple regions of interest as well as smaller surface area in bilateral inferior parietal cortices. However, we found little evidence that these altered cortical metrics mediated the association between lead exposure and decreased cognitive planning. This study suggests that prenatal exposure to lead alters adolescent cortical structure within the planning network, primarily through reduced cortical thickness, but this effect was not sufficient to account for lower performance. Our findings highlight the impact of prenatal lead exposure on brain development, yet the neural bases of lead-related cognitive planning impairments remain unclear.