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Background: The EU LifeCycle Project was launched in 2017 to combine, harmonize, and analyze data from more than 250,000 participants across Europe and Australia, involving cohorts participating in the EU-funded LifeCycle Project. The purpose of this cohort description is to provide a detailed overview of the major measures within mental health domains that are available in 17 European and Australian cohorts participating in the LifeCycle Project. Methods: Data on cognitive, behavioral, and psychological development has been collected on participants from birth until adulthood through questionnaire and medical data. We developed an inventory of the available data by mapping individual instruments, domain types, and age groups, providing the basis for statistical harmonization across mental health measures. Results: The mental health data in LifeCycle contain longitudinal and cross-sectional data from birth throughout the life course, covering domains across a wide range of behavioral and psychopathology indicators and outcomes, including executive function, depression, ADHD, and cognition. These data span a unique combination of qualitative data collected through behavioral/cognitive/mental health questionnaires and examination, as well as data from biological samples and indices in the form of imaging (MRI, fetal ultrasound) and DNA methylation data. Harmonized variables on a subset of mental health domains have been developed, providing statistical equivalence of measures required for longitudinal meta-analyses across instruments and cohorts. Conclusion: Mental health data harmonized through the LifeCycle project can be used to study life-course trajectories and exposure-outcome models that examine early life risk factors for mental illness and develop predictive markers for later-life disease.

Background: road traffic noise is a prevalent and known health hazard. However, little is known yet about its effect on children's cognition. We aimed to study the association between exposure to road traffic noise and the development of working memory and attention in primary school children, considering school-outdoor and school-indoor annual average noise levels and noise fluctuation characteristics, as well as home-outdoor noise exposure. Methods and findings: we followed up a population-based sample of 2,680 children aged 7 to 10 years from 38 schools in Barcelona (Catalonia, Spain) between January 2012 to March 2013. Children underwent computerised cognitive tests 4 times (n = 10,112), for working memory (2-back task, detectability), complex working memory (3-back task, detectability), and inattentiveness (Attention Network Task, hit reaction time standard error, in milliseconds). Road traffic noise was measured indoors and outdoors at schools, at the start of the school year, using standard protocols to obtain A-weighted equivalent sound pressure levels, i.e., annual average levels scaled to human hearing, for the daytime (daytime LAeq, in dB). We also derived fluctuation indicators out of the measurements (noise intermittency ratio, %; and number of noise events) and obtained individual estimated indoor noise levels (LAeq) correcting for classroom orientation and classroom change between years. Home-outdoor noise exposure at home (Lden, i.e., EU indicator for the 24-hour annual average levels) was estimated using Barcelona's noise map for year 2012, according to the European Noise Directive (2002). We used linear mixed models to evaluate the association between exposure to noise and cognitive development adjusting for age, sex, maternal education, socioeconomical vulnerability index at home, indoor or outdoor traffic-related air pollution (TRAP) for corresponding school models or outdoor nitrogen dioxide (NO2) for home models. Child and school were included as nested random effects. The median age (percentile 25, percentile 75) of children in visit 1 was 8.5 (7.8; 9.3) years, 49.9% were girls, and 50% of the schools were public. School-outdoor exposure to road traffic noise was associated with a slower development in working memory (2-back and 3-back) and greater inattentiveness over 1 year in children, both for the average noise level (e.g., ‒4.83 points [95% CI: ‒7.21, ‒2.45], p-value < 0.001, in 2-back detectability per 5 dB in street levels) and noise fluctuation (e.g., ‒4.38 [‒7.08, ‒1.67], p-value = 0.002, per 50 noise events at street level). Individual exposure to the road traffic average noise level in classrooms was only associated with inattentiveness (2.49 ms [0, 4.81], p-value = 0.050, per 5 dB), whereas indoor noise fluctuation was consistently associated with all outcomes. Home-outdoor noise exposure was not associated with the outcomes. Study limitations include a potential lack of generalizability (58% of mothers with university degree in our study versus 50% in the region) and the lack of past noise exposure assessment. Conclusions: we observed that exposure to road traffic noise at school, but not at home, was associated with slower development of working memory, complex working memory, and attention in schoolchildren over 1 year. Associations with noise fluctuation indicators were more evident than with average noise levels in classrooms. This research received funding from the following sources: European Research Council under the ERC Grant Agreement number 268479 (FP7 Ideas) – BREATHE project (JS) and the ERC Grant agreement number 785994 (H2020) - AirNB project (JS), https://erc.europa.eu/. Project "PI16/00118", funded by Instituto de Salud Carlos III and co-funded by European Union (European Regional Development Fund) "A way to make Europe" (JS), www.isciii.es. Agència de Gestió d’Ajuts Universitaris (Beatriu de Pinós fellowship, 2017 BP 00173, MF), https://agaur.gencat.cat/en/Beatriu-de-Pinos. MF is currently supported by an AXA Research Fund grant, https://www.axa-research.org/. We also acknowledge support from the Spanish Ministry of Science and Innovation and State Research Agency through the “Centro de Excelencia Severo Ochoa 2019-2023” Program (CEX2018-000806-S, https://www.ciencia.gob.es/site-web/en/Organismos-y-Centros/Centros-y-Unidades-de-Excelencia.html, and the Generalitat de Catalunya through the CERCA Program (https://cerca.cat/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Epidemiological studies mostly focus on single environmental exposures. This study aims to systematically assess associations between a wide range of prenatal and childhood environmental exposures and cognition. The study sample included data of 1298 mother-child pairs, children were 6–11 years-old, from six European birth cohorts. We measured 87 exposures during pregnancy and 122 cross-sectionally during childhood, including air pollution, built environment, meteorology, natural spaces, traffic, noise, chemicals and life styles. The measured cognitive domains were fluid intelligence (Raven's Coloured Progressive Matrices test, CPM), attention (Attention Network Test, ANT) and working memory (N-Back task). We used two statistical approaches to assess associations between exposure and child cognition: the exposome-wide association study (ExWAS) considering each exposure independently, and the deletion-substitution-addition algorithm (DSA) considering all exposures simultaneously to build a final multiexposure model. Based on this multiexposure model that included the exposure variables selected by ExWAS and DSA models, child organic food intake was associated with higher fluid intelligence (CPM) scores (beta = 1.18; 95% CI = 0.50, 1.87) and higher working memory (N-Back) scores (0.23; 0.05, 0.41), and child fast food intake (−1.25; −2.10, −0.40), house crowding (−0.39; −0.62, −0.16), and child environmental tobacco smoke (ETS) (−0.89; −1.42, −0.35), were all associated with lower CPM scores. Indoor PM2.5 exposure was associated with lower N-Back scores (−0.09; −0.16, −0.02). Additional associations in the unexpected direction were found: Higher prenatal mercury levels, maternal alcohol consumption and child higher perfluorooctane sulfonic acid (PFOS) levels were associated with better cognitive performance; and higher green exposure during pregnancy with lower cognitive performance. This first comprehensive and systematic study of many prenatal and childhood environmental risk factors suggests that unfavourable child nutrition, family crowdedness and child indoor air pollution and ETS exposures adversely and cross-sectionally associate with cognitive function. Unexpected associations were also observed and maybe due to confounding and reverse causality., Graphical abstract Prenatal and childhood exposome-wide associations with child fluid intelligence (CPM). The exposures selected by Deletion-substitution-addition algorithm are represented by a triangle. Child fluid intelligence is mainly associated with childhood exposome, fast-food (negative association, left sided) and organic food consumption (positive, right sided), house crowding (negative, left sided), and child environmental tobacco smoke (ETS, negative, left sided). Image 1, Highlights • Previous evidence for environmental risk factor associations with neurodevelopment is based on analyses of single exposures. • We systematically analysed multiple environmental exposures in relation to child neurodevelopment. • The findings describe a list of outcome-related exposures: Diet, house crowding, indoor air pollution and tobacco smoke. • The findings show methodological complexities of analysing multiple exposures and their associations with neurodevelopment.

The longitudinal study of typical neurodevelopment is key for understanding deviations due to specific factors, such as psychopathology. However, research utilizing repeated measurements remains scarce. Resting-state functional magnetic resonance imaging (MRI) studies have traditionally examined connectivity as ‘static’ during the measurement period. In contrast, dynamic approaches offer a more comprehensive representation of functional connectivity by allowing for different connectivity configurations (time varying connectivity) throughout the scanning session. Our objective was to characterize the longitudinal developmental changes in dynamic functional connectivity in a population-based pediatric sample. Resting-state MRI data were acquired at the ages of 10 (range 8-to-12, n = 3,327) and 14 (range 13-to-15, n = 2,404) years old using a single, study-dedicated 3 Tesla scanner. A fully-automated spatially constrained group-independent component analysis (ICA) was applied to decompose multi-subject resting-state data into functionally homogeneous regions. Dynamic functional network connectivity (FNC) between all ICA time courses were computed using a tapered sliding window approach. We used a k-means algorithm to cluster the resulting dynamic FNC windows from each scan session into five dynamic states. We examined age and sex associations using linear mixed-effects models. First, independent from the dynamic states, we found a general increase in the temporal variability of the connections between intrinsic connectivity networks with increasing age. Second, when examining the clusters of dynamic FNC windows, we observed that the time spent in less modularized states, with low intra- and inter-network connectivity, decreased with age. Third, the number of transitions between states also decreased with age. Finally, compared to boys, girls showed a more mature pattern of dynamic brain connectivity, indicated by more time spent in a highly modularized state, less time spent in specific states that are frequently observed at a younger age, and a lower number of transitions between states. This longitudinal population-based study demonstrates age-related maturation in dynamic intrinsic neural activity from childhood into adolescence and offers a meaningful baseline for comparison with deviations from typical development. Given that several behavioral and cognitive processes also show marked changes through childhood and adolescence, dynamic functional connectivity should also be explored as a potential neurobiological determinant of such changes.

Background: The neurodevelopmental effects of high doses of ionizing radiation (IR) in children are well established. To what extent such effects exist at low-to-moderate doses is unclear. Considering the increasing exposure of the general population to low-to-moderate levels of IR, predominantly from diagnostic procedures, the study of these effects has become a priority for radiation protection. Objectives: We conducted a systematic review of the current evidence for possible effects of low-to-moderate IR doses received during gestation, childhood and adolescence on different domains of neurodevelopment. Data sources: Searches were performed in PubMed, Scopus, EMBASE and Psychinfo on the 6th of June 2017 and repeated in December 2018. Study eligibility criteria: We included studies evaluating the association between low-to-moderate IR doses received during gestation, childhood and adolescence, and neurodevelopmental functions. Study appraisal and synthesis methods: Studies were evaluated using the Cochrane Collaboration′s risk of bias tool adapted to environmental sciences. A qualitative synthesis was performed. Results: A total of 26 manuscripts were finally selected. Populations analyzed in these publications were exposed to the following sources of IR: atomic bomb (Hiroshima and Nagasaki), diagnostic/therapeutic radiation, and Chernobyl and nuclear weapon testing fallout.There was limited evidence for an association between low-to-moderate doses of IR and a decrease in general cognition and language abilities, that is, a causal interpretation is credible, but chance or confounding cannot not be ruled out with reasonable confidence. Evidence for a possible stronger effect when exposure occurred early in life, in particular, during the fetal period, was inadequate. Evidence for an association between IR and other specific domains, including attention, executive function, memory, processing speed, visual-spatial abilities, motor and socio-emotional development, was inadequate, due to the very limited number of studies found. Limitations, conclusions, and implications of key findings: Overall, depending on the domain, there was limited to inadequate evidence for an effect of low-to-moderate IR doses on neurodevelopment. Heterogeneity across studies in terms of outcome and exposure assessment hampered any quantitative synthesis and any stronger conclusion. Future research with adequate dosimetry and covering a range of specific neurodevelopmental outcomes would likely contribute to improve the body of evidence. Systematic review registration number: The systematic review protocol was registered in PROSPERO (registration number CRD42018091902). Keywords: Ionizing radiation, Low dose, Neurodevelopment, Epidemiology, Child health

Background: Although previous studies have reported negative associations between exposure to air pollution and cognition, studies of the effects of prenatal and postnatal exposures in early childhood have been limited. Objectives: We sought to assess the role exposure to fine particulate matter ([Formula: see text]) during different prenatal and postnatal windows may play in children's cognitive development at school age. Methods: Within the Brain Development and Air Pollution Ultrafine Particles in School Children (BREATHE) Project, we estimated residential [Formula: see text] exposures by land use regression for the prenatal period and first seven postnatal years of 2,221 children from Barcelona, Spain. The participants ([Formula: see text]) completed computerized tests assessing working memory, attentiveness, and conflict network during four visits in 2012–2013. We used linear mixed effects and distributed lag models to assess the period of exposure to [Formula: see text] in association with cognitive development. Results: Inverse associations were identified between [Formula: see text] exposure during the fifth and sixth postnatal years and working memory, with boys showing much higher vulnerability. Regarding attention functions, exposure to higher [Formula: see text] levels during the prenatal period and from the fourth postnatal year were associated with a reduction in conflict network performance, though we found no association with attentiveness. The overall estimated cumulative effect of a [Formula: see text] increase in [Formula: see text] resulted in a reduction in the working memory [Formula: see text] score of [Formula: see text] [95% confidence interval (CI): [Formula: see text], [Formula: see text]] points and an increase in the conflict attentional network of 11.31 (95% CI: 6.05, 16.57) milliseconds, indicating a poorer performance. Conclusions: Early life exposure to [Formula: see text] was associated with a reduction in fundamental cognitive abilities, including working memory and conflict attentional network. https://doi.org/10.1289/EHP3169. The research leading to these results has received funding from the European Research Council (ERC-Advanced Grant) under grant agreement number 268479—the BREATHE project. We are grateful to A. Dalmau-Bueno for his help in estimating exposure to air pollution. We thank all the families participating in the study and particularly to the schools. P.D. is funded by a Juan de la Cierva fellowship (JCI-2011-09937) awarded by the Spanish Ministry of Science and Innovation.

This study was funded by Grants from Spanish Institute of Health Carlos III-Ministry of Economy and Competitiveness (INMA Network G03/176, CB06/02/0041, and FIS-FEDER: PI03/1615, PI04/1436, PI08/1151, PI04/2018, PI04/1509, PI04/1112, PI04/1931, PI05/1079, PI05/1052, PI06/1213, PI06/0867, PI07/0314, PI09/02647, PS09/00090, PI09/02311, MS11/0178, PI13/1944, PI13/2032, PI13/02429, PI16/1288, and PI17/00663), Generalitat de CatalunyaCIRIT 1999SGR 00241, JCI-2011–09771–MICINN, Generalitat Valenciana (Conselleria de Sanitat-048/2010 and 060/2010 and FISABIO-UGP 15-230, 15-244, and 15-249), Alicia Koplowitz Foundation, Universidad de Oviedo, Fundación Cajastur-Liberbank, Department of Health of the Basque Government (2005111093 and 2009111069), the Provincial Government of Gipuzkoa (DFG06/004 and DFG08/001), and the Fundación Roger Torné. This study has been funded by Instituto de Salud Carlos III through the projects “CP14/00108 & PI16/00261” (Co-funded by European Regional Development Fund “A way to make Europe”). Jordi Julvez, Mònica Guxens and MariaJose Lopez-Espinosa hold a Miguel Servet contract (MS14/00108, MS13/00054 and MSII16/00051, respectively) awarded by the Spanish Institute of Health Carlos III (Ministry of Economy and Competitiveness)., Gignac, F., Romaguera, D., Fernández-Barrés, S., Phillipat, C., Garcia Esteban, R., López-Vicente, M., Vioque, J., Fernández-Somoano, A., Tardón, A., Iñiguez, C., Lopez-Espinosa, M.-J., García de la Hera, M., Amiano, P., Ibarluzea, J., Guxens, M., Sunyer, J., Julvez, J.

There is increase concerns over child behavioral problems due to changing environments. Children are typically exposed to a long list of industrial chemicals that are neurotoxic but also to benefic...

Background: Prospective longitudinal studies are essential in characterizing cognitive trajectories, yet few of them have been reported on the development of attention processes in children. We aimed to explore attention development in normal children and children with attention deficit and hyperactivity disorder (ADHD) symptoms in a repeated measures design using the attention network test (ANT). Methods: The population sample included 2,835 children (49.6% girls) aged 7–11 years from 39 schools in Barcelona (Catalonia, Spain) who performed the ANT four times from January 2012 to March 2013. According to teacher ratings, 10.5% of the children presented ADHD symptoms. We performed multilevel mixed-effects linear regression models, adjusting for school and individual, to test the effects of age-related growth on the ANT networks: alerting, orienting and executive attention, and three measurements related to attentiveness: median of hit reaction time (HRT), hit reaction time standard error (HRT-SE) and variability. Results: We observed age-related growth in all the outcomes, except orienting. The curves were steeper at the younger groups, although for alertness the improvement was further at the oldest ages. Gender and ADHD symptoms interacted with age in executive attention, HRT and variability. Girls performed better in executive attention at young ages although boys reached females at around 10 years of age. For HRT, males showed faster HRT. However, girls had a more pronounced improvement and reached the levels of boys at age 11. Children with ADHD symptoms had significant differences in executive attention, HRT and variability compared to children without ADHD symptoms. Conclusions: We detected an ongoing development of some aspects of attention in primary school children, differentiating patterns by gender and ADHD symptoms. Our findings support the ANT for assessing attention processes in children in large epidemiological studies. The research leading to these results received funding from the European Research Council under the ERC Grant Agreement number 268479 – the BREATHE project. JJ holds a Miguel Servet contract (MS14/00108) awarded by the Spanish Institute of Health Carlos III (Ministry of Economy and Competitiveness).

Introduction Recently, we showed that exposure to traffic-related air pollutants (TRAPs) at school was negatively associated with cognitive development, specifically working memory and inattentiveness, in primary schoolchildren during a course of 12 months. The persistence of such associations over longer periods remains as an open question. Objective To study the longitudinal association between TRAPs at school and cognitive development over a period of 3.5 years. Methods Indoor and outdoor levels of TRAPs (elemental carbon (EC), dioxide nitrogen (NO 2 ), particulate matter (PM 2.5 ) from traffic sources and ultrafine particles (UFP)) were measured at 39 schools across Barcelona during 2012/2013. Working memory, as a measure of cognitive development, was evaluated 4 times in 2012/2013 assessment and was re-evaluated one more time in 2015 using computerized n-back test (3-back d′ as main outcome). Linear mixed effects models were used to test the association between TRAPs and 3-back d′, adding child and school as random effects to account for the multilevel nature of the data, and school air pollutants levels (one at a time) as predictor. Results We found detrimental associations between all TRAPs and annual change in 3-back d′ (working memory) (i.e. slower development of working memory in children attending schools with higher levels of air pollution). The associations (per one interquartile range increase in exposure) were strongest for outdoor NO 2 (Coefficient (Coef) = − 4.22, 95% confidence interval (CI), − 6.22, − 2.22) and indoor UFP (Coef = − 4.12, 95%CI, − 5.68, − 1.83). These reductions were equivalent to − 20% (95%CI, − 30.1, − 10.7) and − 19.9% (95%CI, − 31.5, − 8.4) change in annual working memory development associated with one interquartile range increase in outdoor NO 2 and indoor UFP, respectively. Conclusion Our findings suggest the persistence of the negative association between TRAPs exposure at school and cognitive trajectory measured by n-back test over a period of 3.5 years.

Purpose:The evidence regarding the role of physical activity (PA) habits on cognitive development in children is still scarce. Our study aimed to assess the association between PA habits and cognitive growth patterns, including working memory (WM) and inattentiveness in a large sample of primary schoolchildren.Method:This study included 2,897 children between 7 and 10 years old. WM was measured using the n-back task (2- and 3-back) and inattentiveness was measured using the attentional network task (ANT) on four occasions during one year. Parents completed a questionnaire with data about the extracurricular exercise of their child, commuting to school and other sociodemographic information at the first visit.Results:Exercising twice per week or more was associated with better 2-back, 3-back and inattentiveness scores at baseline, as compared with the once per week or less category. Active commuting for more than 50 min was associated with better 3-back scores at baseline, as compared with passive commuting. No consistent associations were found between PA and cognitive growth.Conclusion:Overall, although children with high levels of PA performed better in cognitive tasks at baseline, PA levels had no clear effects on cognitive growth trajectories.

Background Air pollution is a suspected developmental neurotoxicant. Many schools are located in close proximity to busy roads, and traffic air pollution peaks when children are at school. We aimed to assess whether exposure of children in primary school to traffic-related air pollutants is associated with impaired cognitive development. Methods and Findings We conducted a prospective study of children (n = 2,715, aged 7 to 10 y) from 39 schools in Barcelona (Catalonia, Spain) exposed to high and low traffic-related air pollution, paired by school socioeconomic index; children were tested four times (i.e., to assess the 12-mo developmental trajectories) via computerized tests (n = 10,112). Chronic traffic air pollution (elemental carbon [EC], nitrogen dioxide [NO2], and ultrafine particle number [UFP; 10–700 nm]) was measured twice during 1-wk campaigns both in the courtyard (outdoor) and inside the classroom (indoor) simultaneously in each school pair. Cognitive development was assessed with the n-back and the attentional network tests, in particular, working memory (two-back detectability), superior working memory (three-back detectability), and inattentiveness (hit reaction time standard error). Linear mixed effects models were adjusted for age, sex, maternal education, socioeconomic status, and air pollution exposure at home. Children from highly polluted schools had a smaller growth in cognitive development than children from the paired lowly polluted schools, both in crude and adjusted models (e.g., 7.4% [95% CI 5.6%–8.8%] versus 11.5% [95% CI 8.9%–12.5%] improvement in working memory, p = 0.0024). Cogently, children attending schools with higher levels of EC, NO2, and UFP both indoors and outdoors experienced substantially smaller growth in all the cognitive measurements; for example, a change from the first to the fourth quartile in indoor EC reduced the gain in working memory by 13.0% (95% CI 4.2%–23.1%). Residual confounding for social class could not be discarded completely; however, the associations remained in stratified analyses (e.g., for type of school or high-/low-polluted area) and after additional adjustments (e.g., for commuting, educational quality, or smoking at home), contradicting a potential residual confounding explanation. Conclusions Children attending schools with higher traffic-related air pollution had a smaller improvement in cognitive development., In a prospective cohort study, Jordi Sunyer and colleagues examine the association between traffic-related air pollution and 12 month cognitive development trajectories in primary school children in Barcelona., Editors' Summary Background Human brain development is a complex and lengthy process. During pregnancy, the basic structures of the brain are formed, and the neural circuits that will eventually control movement, speech, memory, and other cognitive (thinking) functions, as well as the function of many organs, begin to be established. By the time of birth, the brain is about a quarter of its adult size, and the neural circuits that control vital bodily functions such as breathing are well developed. By contrast, the cerebral cortex—the brain region that is involved in thought and action—is poorly developed. Much of the development of the cerebral cortex happens during the first two years of life. For example, babies usually learn to crawl at about nine months. Other aspects of brain function take longer to develop. Thus, the cognitive functions that are essential for learning undergo considerable development between the ages of 6 and 10 years, and further brain changes occur during adolescence. Why Was This Study Done? Exposure to the air pollutants produced by the combustion of fossil fuels by vehicles during pregnancy or infancy has been associated with delays in cognitive development. Moreover, experiments in animals suggest that traffic-related air pollution is a developmental neurotoxicant—a factor that disrupts brain development. However, although many schools are located next to busy roads and although traffic-related air pollution levels peak during school hours, it is not known whether exposure of school-age children to traffic-related air pollutants impairs their cognitive development and thus their ability to learn. Here, in a prospective cohort study (the BREATHE study), the researchers assess whether exposure of children aged 7–10 years to traffic-related air pollutants in schools in Barcelona, Spain, is associated with impaired cognitive development. A prospective cohort study is an observational investigation that studies groups (cohorts) of individuals who differ with respect to a specific factor to determine how exposure to this factor affects specific outcomes. What Did the Researchers Do and Find? The researchers used computerized tests to measure the development of working memory (the system that holds multiple pieces of transitory information in the mind where they can be manipulated), superior working memory (working memory that involves continuous updating of the working memory buffer), and attentiveness every three months over a 12-month period in 2,715 primary school children attending 39 schools exposed to high or low levels of traffic-related air pollution and paired by socioeconomic index. That is, the researchers compared three cognitive development outcomes in the children attending each school where exposure to air pollution was high with the same outcomes in children attending a school with a similar socioeconomic index where exposure to pollution was low; school pairing was undertaken to avoid “confounding” by social class, a factor that is known to affect cognitive development. Statistical analyses of these data indicated that the increase in cognitive development over time among children attending highly polluted schools was less than that among children attending paired lowly polluted schools, even after adjusting for additional factors that affect cognitive development. Thus, for example, there was an 11.5% 12-month increase in working memory at the lowly polluted schools but only a 7.4% 12-month increase in working memory at the highly polluted schools. Other analyses indicated that children attending schools with higher levels of traffic-related air pollutants in either the courtyard or in the classroom experienced a substantially smaller increase over the 12-month study in all three cognitive measurements than those attending schools with lower levels of pollutants. What Do These Findings Mean? These findings suggest that, compared with attendance at schools exposed to low levels of traffic-related air pollution, attendance at schools exposed to high levels of traffic-related air pollution is associated with a smaller increase in cognitive development over a 12-month period among 7- to 10-year-old children in Barcelona. The accuracy of these findings may be limited by residual confounding. That is, the children attending schools where traffic-related pollution is high might have shared other unknown characteristics that affected their cognitive development. Importantly, these findings do not prove that traffic-related air pollution causes impairment of cognitive development. Rather, they suggest that the developing brain may be vulnerable to traffic-related air pollution well into middle childhood, a conclusion that has implications for the design of air pollution regulations and for the location of new schools. Additional Information Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001792. The US Centers for Disease Control and Prevention provides information about child development, including information about middle childhood (in English and Spanish) Tox Town is an interactive site that provides information about toxic chemicals and environmental health risks, including air pollution The US Environmental Protection Agency provides information about air pollution near roadways and health Wikipedia has pages on cognitive development and on air pollution (note that Wikipedia is a free online encyclopedia that anyone can edit; available in several languages) MedlinePlus provides links to additional resources about air pollution (in English and Spanish) The Centre for Research in Environmental Epidemiology website provides more information about the BREATHE study

Objective To evaluate the role of extracurricular physical activity and sedentary behavior at preschool and primary school age on working memory at primary school age and adolescence, respectively. Study design This prospective study was based on a birth cohort across 4 Spanish regions. In the 3 younger subcohorts (n = 1093), parents reported lifestyle habits of child at age 4 years of age on a questionnaire, and children performed a computerized working memory task at 7 years of age. In the older subcohort (n = 307), the questionnaire was completed at 6 years of age and working memory was tested at 14 years of age. Adjusted regression models were developed to investigate the associations between lifestyle habits and working memory. Results Low extracurricular physical activity levels at 4 years of age were associated with a nonsignificant 0.95% (95% CI −2.81 to 0.92) reduction of correct responses in the working memory task at age 7 years of age. Low extracurricular physical activity levels at 6 years of age were associated with a 4.22% (95% CI −8.05 to −0.39) reduction of correct responses at age 14 years. Television watching was not associated with working memory. Other sedentary behaviors at 6 year of age were associated with a 5.07% (95% CI −9.68 to −0.46) reduction of correct responses in boys at 14 years of age. Conclusion Low extracurricular physical activity levels at preschool and primary school ages were associated with poorer working memory performance at primary school age and adolescence, respectively. High sedentary behavior levels at primary school age were related negatively to working memory in adolescent boys.

Objective: This study aimed to assess the association between attention-deficit hyperactivity disorder (ADHD) symptoms at preschool age and attention functioning at 11 years old. Method: Four-year-old children (n 422) were assessed using the Diagnostic and Statistical Manual of Mental Disorders (4th ed.; American Psychiatric Association, 1994) ADHD form list for inattention and hyperactivity symptoms. Cognitive development and social behavior were also assessed at this age. The Continuous Performance Test II (CPT-II) was used to assess attention function when the children were 11 years old. Results: The presence of inattention symptoms predicted more omission errors (incidence rate ratio [IRR] 1.07, 95% CI [1.02, 1.12]) and slower hit reaction time (HRT; 3.27, 95% CI [0.72, 5.81]) in CPT-II. Both inattention and hyperactivity symptoms predicted greater standard error in the HRT (HRT [SE]) (IRR 1.02, 95% CI [1.01, 1.03]). The inclusion of social competence and cognitive scores in the multivariate regression models diminished the association with omissions, whereas their inclusion did not change associations with the two HRT outcomes. Stronger associations between inattention symptoms and HRT were observed in the last 2 time-duration blocks of the CPT-II. No associations were found with commissions and detectability. Conclusions: The presence of ADHD symptoms in preschool children was longitudinally associated with a lower performance on the CPT-II. Omission errors seemed to be partly explained by early social and cognitive competences. Slower HRTs showed a direct association with inattention symptoms, particularly in the latest CPT-II blocks. HRT (SE) was strongly related to hyperactivity symptoms.

BACKGROUND: Neuropsychological instruments to assess cognitive trajectories during childhood in epidemiological studies are needed. This would improve neurodevelopment characterization in order to identify its potential determinants. We aimed to study whether repeated measures of n-back, a working memory task, detect developmental trajectories in schoolchildren during a 1-year follow-up. METHODS: We administered the n-back task to 2897 healthy children aged 7-11 years old from 39 schools in Barcelona (Spain). The task consisted of 2 levels of complexity or loads (2- and 3-back) and 2 different stimuli (numbers and words). Participants performed the task four times from January 2012 to March 2013. To study the trajectories during the follow-up, we performed linear mixed-effects models including school, individual and age as random effects. RESULTS: We observed improvements related to age in n-back outcomes d', HRT and accuracy, as well as reduced cognitive growth at older ages in d' and HRT. Greater improvements in performance were observed at younger ages, in 2-back, in verbal rather than numerical stimuli and in girls compared to boys. Boys responded faster at baseline, while girls showed increased growth in 2-back numbers. Children with ADHD (Attention Deficit and Hyperactivity Disorder) symptoms (15% of boys and 6% of girls) had a lower working memory at baseline, but they showed similar cognitive growth trajectories in numbers variants of the task, as compared to children without ADHD symptoms. However, the age-related improvement in response speed was not observed in children with ADHD symptoms. CONCLUSIONS: Changes in n-back outcomes reflected developmental trajectories in 1-year follow-up. The present results suggest that the repeated administration of this task can be used to study the factors that may alter the cognitive development during childhood.

A few studies have found associations between the exposure to traffic-related air pollution at school and/or home and cognitive development. The impact on cognitive development of the exposure to air pollutants during commuting has not been explored. We aimed to assess the role of the exposure to traffic-related air pollutants during walking commute to school on cognitive development of children. We performed a longitudinal study of children (n = 1,234, aged 7-10 y) from 39 schools in Barcelona (Catalonia, Spain) who commuted by foot to school. Children were tested four times during a 12-month follow-up to characterize their developmental trajectories of working memory (d' of the three-back numbers test) and inattentiveness (hit reaction time standard error of the Attention Network Test). Average particulate matter ≤2.5 μm (PM2.5), Black Carbon (BC) and NO2 concentrations were estimated using Land Use Regression for the shortest walking route to school. Differences in cognitive growth were evaluated by linear mixed effects models with age-by-pollutant interaction terms. Exposure to PM2.5 and BC from the commutes by foot was associated with a reduction in the growth of working memory (an interquartile range increase in PM2.5 and BC concentrations decreased the annual growth of working memory by 5.4 (95% CI [-10.2, -0.6]) and 4.6 (95% CI [-9.0, -0.1]) points, respectively). The findings for NO2 were not conclusive and none of the pollutants were associated with inattentiveness. Efforts should be made to implement pedestrian school pathways through low traffic streets in order to increase security and minimize children's exposure to air pollutants. The research leading to these results has received funding from the European Community's Seventh Framework Program (ERC-Advanced Grant) under grant agreement number 268479 - the BREATHE project