Manganese (Mn) is an essential nutrient that is neurotoxic at high levels of exposure. Prenatal and childhood Mn exposure is associated with impaired self-control in adolescents, including poor working memory. Little is known about the effects of early-life exposure on substance use, a prevalent impulsive behavior in adolescents, and its underlying neural mechanisms. The aim of the proposed study is to examine whether early-life Mn exposure is associated with substance use, functional activity and connectivity of self-control brain areas (e.g., prefrontal cortex, parietal cortex) in adolescents. We will invite 120 adolescents (15-22 years) to participate in a functional magnetic resonance imaging (fMRI) study that includes a working memory task and a resting state scan (to assess intrinsic functional connectivity of the brain). Participants will further report their recent smoking and alcohol use. Participants are living in three different areas in Northern Italy, with either high, moderate or no Mn contamination. Mn exposure during pregnancy and childhood will be determined using an innovative biomarker of exposure, baby teeth, allowing us to identify windows of vulnerability. The proposed host institute is the Icahn School of Medicine at Mount Sinai in New York.