Research | Children’s Health Response Inhibition and Error Monitoring during a Visual Go/No-Go Task in Inuit Children Exposed to Lead, Polychlorinated Biphenyls, and Methylmercury Olivier Boucher,1 Matthew J. Burden,2 Gina Muckle,1,3 Dave Saint-Amour,4,5 Pierre Ayotte,1,3 Éric Dewailly,1,3 Charles A. Nelson,6 Sandra W. Jacobson,2 and Joseph L. Jacobson 2 1Centre de recherche du Centre Hospitalier Universitaire de Québec, Québec, Canada; 2Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, Michigan, USA; 3Université Laval, Québec, Canada; 4Centre de recherche, Hôpital Sainte-Justine, Montréal, Québec, Canada; 5Département de psychologie, Université du Québec à Montréal, Montréal, Québec, Canada; 6Children’s Hospital Boston/Harvard Medical School, Boston, Massachusetts, USA Background : Lead (Pb) and polychlorinated biphenyls (PCBs) are neurotoxic contaminants that have been related to impairment in response inhibition. o Bjectivs : In this study we examined the neurophysiological correlates of the response inhibition deficits associated with these exposures, using event-related potentials (ERPs) in a sample of school- age Inuit children from Arctic Québec exposed through their traditional diet. Methods : In a prospective longitudinal study, we assessed 196 children (mean age, 11.3 years) on a visual go/no-go response inhibition paradigm. Pb, PCB, and mercury (Hg) concentrations were analyzed in cord and current blood samples. Hierarchical multiple regression analyses were con- ducted to examine the associations of contaminant levels to go/no-go performance (mean reaction time, percent correct go, percent correct no-go) and five ERPs [N2, P3, error-related negativity, error positivity (Pe), and correct response positivity (Pc)] after control for confounding variables. r esult : Current blood Pb concentrations were associated with higher rates of false alarms and with decreased P3 amplitudes to go and no-go trials. Current plasma PCB-153 concentrations were associated with slower reaction times and with reduced amplitudes of the Pe and Pc response- related potentials. Hg concentrations were not related to any outcome on this task but showed sig- nificant interactions with other contaminants on certain outcomes. words c onclusi : These results suggest that Pb exposure during childhood impairs the child’s abil - ity to allocate the cognitive resources needed to correctly inhibit a prepotent response, resulting in increased impulsivity. By contrast, postnatal PCB exposure appears to affect processes associated with error monitoring, an aspect of behavioral regulation required to adequately adapt to the chang- ing demands of the environment, which results in reduced task efficiency. k ey : event-related potentials, error monitoring, executive function, lead, methylmercury, neurotoxicity, polychlorinated biphenyls, response inhibition. Environ Health Perspect 120:608–615 (2012). http://dx.doi.org/10.1289/ehp.1103828 [Online 5 December 2011] Lead (Pb) and polychlorinated biphenyls (PCBs) are widespread environmental con- taminants known for their developmental neurotoxicity. Despite differences in their chemical structures and properties, early expo- sure to these pollutants appears to produce similar effects on neurobehavior, including impulsivity, hyperactivity, and impairment in executive function (Boucher et al. 2009a; Brockel and Cory-Slechta 1998; Nicolescu et al. 2010; Rice 1999). These effects have been hypothesized to reflect dysfunction of the prefrontal cortex (Levin et al. 1992; Meng et al. 2005) and alterations in dopamine func- tion (Seegal et al. 1997; White et al. 2007). The term “executive function” refers to a set of cognitive processes involved in goal- directed behaviors, which are often elicited in new and/or complex situations (Norman and Shallice 1986). One key component of executive function is the ability to inhibit dominant or prepotent responses when necessary (Miyake et al. 2000), and impair- ment in this ability can result in impulsivity. Studies investigating the relation of Pb and PCB exposure to impulsivity and executive 608 function have relied exclusively on neuro- psychological and observational assessments. Because of their high temporal resolution, event-related potentials (ERPs) make it pos- sible to evaluate children’s performance in specific response components arrayed across time. ERPs recorded during a task requiring response inhibition could help in understand- ing the neurobehavioral effects associated with Pb and PCB exposures in children. The Inuit from Nunavik (Arctic Québec, Canada) are among the most heavily exposed populations on earth to PCBs and methyl- mercury (MeHg) because of the long-range transport of these chemicals via atmospheric and ocean currents and their bioaccumulation in fish and sea mammals that are staples of the traditional Inuit diet (Muckle et al. 2001). Pb exposure is also a concern because of the use of Pb cartridges for game bird hunting despite governmental regulations designed to dis- courage their use (Lévesque et al. 2003). This study was designed to examine the relation of exposure to these environmental contami- nants to response inhibition and executive control of behavior using ERPs recorded during a visual go/no-go task in a sample of school-age Inuit children participating to a birth-cohort study. Go/no-go tasks typi- cally require a participant to press a button in response to a given set of stimuli (“go” condi- tion) and to inhibit that action (not to press the same button) in response to a different set of stimuli (“no-go” condition). The go/no-go task employed in this study was developed for functional magnetic reso- nance imaging by Casey et al. (1997), who reported increased prefrontal cortex activ- ity during response inhibition. The task was adapted for ERPs by Davis et al. (2003), who examined two late-latency components in relation to response inhibition, the N2 and the P3. The N2 is maximal > 300 msec poststimulus over frontal electrode locations and has been attributed to conflict detec- tion or to the decision to withhold a motor response (Falkenstein 2006). The P3, maxi- mal approximately 500 msec poststimulus at centroparietal electrodes, shows enhanced activity for no-go stimuli and is thought to reflect the amount of resources needed for task processing and/or efficiently inhibiting a motor response (Davis et al. 2003). Error monitoring is another aspect of the executive control that can be assessed using ERPs. ERPs recorded after erroneous responses show two successive components, “error-related negativity” (ERN) and “error positivity” (Pe). Address correspondence to J.L. Jacobson, Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, 2751 E Jefferson, Suite 460, Detroit, MI 48202 USA. Telephone: (313) 993-5454. Fax: (313) 993-3427. E-mail: joseph.jacobson@wayne.edu We are grateful to the Nunavik population and to all the people involved in this study. We thank R. Sun, L. Roy, J. Varin, B. Tuttle, A. Pov, A. Westerlund, J. Gagnon, N. Dodge, and C. Bastien for their valu- able contributions. This study was funded by grants from National Institutes of Health (NIH)/National Institute of Environmental Health Sciences grant R01-ES007902 (J.L.J.), Northern Contaminants Program, Indian and Northern Affairs Canada (G.M.), NIH/National Institute on Alcohol Abuse and Alcoholism grant F32-AA14730 (M.J.B.), and the Joseph Young, Sr., Fund from the State of Michigan (S.W.J.). The authors declare they have no actual or potential competing financial interests. Received 15 April 2011; accepted 5 December 2011. ovlume 120 | number 4 | April 2012 • Environmental Health Perspectives