Boucher et al. that adverse effects of childhood Pb exposure are detected more readily when higher-order, executive processes (i.e., response inhibition) are elicited. This inference is also supported by the finding that the association of postnatal Pb with P3 amplitude was more marked in the no-go than in the go condition. Impulse control and inhibition have been shown to be specifically impaired in Pb-exposed ani- mals (Brockel and Cory-Slechta 1998), and evidence is accumulating that these aspects of cognition are among the most sensi- tive to Pb exposure in children. Higher rat- ings of impulsive and inattentive behavior, impaired response inhibition, and increased risk of attention deficit hyperactivity disor- der have been reported in samples of children with mean blood Pb concentrations as low as ≤ 5 μg/dL (Froehlich et al. 2009; Nicolescu et al. 2010; Stewart et al. 2006; Surkan et al. 2007). These effects suggest enhanced vulner- ability of the prefrontal cortex to Pb neuro- toxicity during childhood, a hypothesis that has been supported by imaging studies reveal- ing specific structural (Cecil et al. 2008) and metabolic (Cecil et al. 2011; Meng et al. 2005) Pb-associated alterations in this region of the brain. The present study adds to this evidence by reporting an inverse relation between blood Pb levels (< 5 μg/dL) and amplitude of the no-go P3 ERP component, which is believed to be generated within the prefrontal cortex (Davis et al. 2003). These effects, observed at such low Pb levels, also strengthen the argu- ments for revising the blood Pb concentra- tions considered “acceptable” by public health agencies from 10 μg/dL (Centers for Disease Control and Prevention 1991; Health Canada 1994) to a lower value. The mean blood Pb concentration in this study is similar to that reported for preschool children from the gen- eral U.S. population during the mid-1990s (Jones et al. 2009), which adds to the grow- ing body of evidence that a large proportion of children exposed at levels considered safe under current public health recommenda- tions actually show subtle adverse effects from Pb neurotoxicity (e.g., Chiodo et al. 2004; Lanphear et al. 2000). In this study, cord blood Pb concentra- tions were associated with increased errors in both the go and no-go trials. This pattern of results may reflect an effect of prenatal Pb exposure on attention and cognitive function generally rather than the specific effect on response inhibition seen in relation to cur- rent Pb only on the no-go trials. This may explain why no effect of prenatal Pb exposure was observed on the ERP measures. Adverse effects of prenatal Pb exposure on attention have been reported in previous assessments conducted on this same cohort of children (Boucher et al. 2009b; Plusquellec et al. 2007). Although no adverse behavioral effects 614 were seen in relation to prenatal PCB expo- sure on this relatively simple task, the ERP data suggest impairment in processing that would be expected to affect performance in a more challenging task. The delayed RTs and reduced Pe/Pc amplitudes seen in relation to postnatal PCB exposure in this study suggest that PCB expo- sure alters the neural processes involved in error monitoring. Neural generators of the Pe have been localized, notably, in the rostral portion of the anterior cingulate cortex (ACC) (Herrmann et al. 2004; Van Veen and Carter 2002). Lesions involving the rostral ACC have been associated with impairment in the regulation of cognitive control after response conflict, leading to poor context-dependent adjustments of behavior (Di Pellegrino et al. 2007). Poorer behavioral regulation in rela- tion to contextual information, such as pre- vious errors, might account for the high sensitivity of delayed reinforcement paradigms and of tasks assessing planning and response inhibition to early PCB exposure (Jacobson and Jacobson 1996, 2003; Lilienthal et al. 1990; Rice 1999; Stewart et al. 2005, 2006; Vreugdenhil et al. 2004). Most previous birth cohort studies on PCB neurotoxicity have reported adverse effects of prenatal but not postnatal PCB exposure on cognition (e.g., Boucher et al. 2009a; Jacobson and Jacobson 1996; Jacobson et al. 1985). The effects associated with postnatal PCB expo- sure in this study are likely explained by the typically longer period of breast-feeding in this Inuit sample and the substantial quanti- ties of PCB-contaminated traditional Inuit food eaten by these children than that seen in U.S. and southern Canadian children. This extended breast-feeding likely has led to post- natal transmission of much larger quantities of these contaminants than in other PCB cohort studies. Adverse neurobehavioral effects of postnatal PCB have been demonstrated in experimental studies with animals (e.g., Rice 1999), supporting the plausibility of adverse effects from postnatal PCB exposure when the levels are sufficiently high. Although cord and child Hg levels were correlated with some of the behavioral and ERP measures, virtually none of these asso- ciations remained significant once other con- taminants or covariates were included in the analysis. The synergistic effects between cord Hg and cord PCB seen on some neurobehav- ioral end points by Grandjean et al. (2001) were not seen consistently in this study. Although the stratified analyses indicated effects of cord Hg on three ERP measures in the children with heavier prenatal PCB expo- sures, the effect on a fourth ERP measure was stronger in children with lower prenatal PCB exposure. It has been suggested that statisti- cal control for seafood nutrients, such as the polyunsaturated fatty acid DHA, may provide a better estimation of the effects of MeHg exposure (Budtz-Jørgensen et al. 2007). The absence of clear effects even after statistical control for DHA in the present study there- fore provides additional support for the con- clusion that response inhibition and error monitoring are not specific targets of MeHg neurotoxicity in children. Conclusion This study was designed to examine the neuro- physiological correlates of response inhibi- tion impairment associated with Pb and PCB exposures in children. The results suggest that childhood Pb exposure specifically impairs the allocation of the resources needed for correctly inhibiting a prepotent response, which results in increased impulsivity. By contrast, postnatal PCB exposure appears to affect the processes associated with error monitoring, an aspect of behavioral regulation required to adequately adapt to the changing demands of the envi- ronment, which has been localized within the ACC. This effect results in reduced task effi- ciency and may play a role in the PCB-related cognitive impairments reported in previous studies. The present data demonstrate the util- ity of ERPs in advancing understanding of the mechanisms underlying the neurotoxicity of environmental contaminants. Ref Rencs Ayotte P, Muckle G, Jacobson JL, Jacobson SW, Dewailly É. 2003. 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PLoS Med 5:741–750. ovlume 120 | number 4 | April 2012 • Environmental Health Perspectives