Pre-natal and early life lead exposure and childhood inhibitory control: an item response theory approach to improve measurement precision of inhibitory control.

BACKGROUND: Neurodevelopmental performance tasks are often separately analyzed, even when they tap into a similar construct. This may yield mixed findings for associations of an exposure-neurobehavioral outcome. We develop an item response theory (IRT) approach to integrate multiple task variables together to improve measurement precision of the underlying construct. We apply this approach to create an integrative measure of childhood inhibitory control, and study impacts of pre/post-natal lead exposure. METHODS: Using data from a prospective cohort based in Mexico (N = 533), we created an inhibitory control scale that integrates accuracy and reaction time information from four inhibitory control tasks (Go/NoGo Letter, Go/NoGo Neutral, Go/NoGo Happy, Delis-Kaplan Executive Function System (D-KEFS) Color-Word Interference Test, Condition 3). Using a generalized partial credit item response theory model, we estimated an inhibitory control index for each participant. We then assessed adjusted associations between umbilical cord blood and 4-year lead and childhood inhibitory control. We developed a resampling approach to incorporate error estimates from the inhibitory control variable to confirm the consistency of the lead-inhibitory control associations. We modeled time-varying associations of lead with each inhibitory control measure separately. RESULTS: Participants had a median age of 9 years; 51.4% were males. Umbilical cord blood [-0.06 (95% CI: -0.11, -0.01)] and 4-year lead [-0.07 (95% CI: -0.12, -0.02)] were associated with inhibitory control index at 8-10 years. A resampling approach confirmed that 4-year lead was consistently associated with childhood inhibitory control index. Umbilical cord blood and 4-year lead were each associated with 3 out of 8 measures in separate models. CONCLUSION: This is the first application of IRT in environmental epidemiology to create a latent variable for inhibitory control that integrates accuracy and reaction time information from multiple, related tasks. This framework can be applied to other correlated neurobehavioral assessments or other phenotype data.

Racial and ethnic disparities in psychological care for individuals with FASD: a dis/ability studies and critical race theory perspective toward improving prevention, assessment/diagnosis, and intervention.

Fetal alcohol spectrum disorders (FASD) are among the most common neurodevelopmental disorders and substantially impact public health. FASD can affect people of all races and ethnicities; however, there are important racial and ethnic disparities in alcohol-exposed pregnancy prevention, assessment and diagnosis of FASD, and interventions to support individuals with FASD and their families. In this article we use the Dis/Ability Studies and Critical Race Theory (Dis/Crit) framework to structure the exploration of disparities and possible solutions within these three areas (prevention, diagnosis, intervention). Dis/Crit provides a guide to understanding the intersection of dis/ability and race, while framing both as social constructs. Following the Dis/Crit framework, the systemic, historical, and contemporary racism and ableism present in psychological care is further discussed. We aim to elucidate these racial and ethnic disparities within the fields of psychology and neuropsychology through the Dis/Crit framework and provide potential points of action to reduce these disparities.

Normative Magnetic Resonance Imaging Data Increase the Sensitivity to Brain Volume Abnormalities in the Classification of Fetal Alcohol Spectrum Disorder.

OBJECTIVE: To evaluate the use of a large magnetic resonance imaging (MRI) normative dataset to quantify structural brain anomalies that may improve diagnostic sensitivity for atypical brain volume in youth with fetal alcohol spectrum disorder (FASD). STUDY DESIGN: Participants included 48 children with prenatal alcohol exposure (PAE) and 43 controls, ages 8-17 years, from the longitudinal Collaborative Initiative on FASD s. Recently published lifespan brain charts were used to quantify participants' (per)centile for brain volumes (cortical and subcortical gray matter and cortical white matter), providing an index of (dis)similarity to typically developing individuals of the same age and sex. RESULTS: Participants with PAE demonstrated lower mean centile scores compared with controls. Participants with PAE and scores ≤ 10th centile on at least 1 brain volume metric demonstrated significantly lower performance on measures of intellectual function and aspects of executive functioning compared with participants with PAE and "typical" volumes (>10th centile). Brain volume centiles explained a greater amount of variance in IQ and improved sensitivity to brain volume anomalies in FASD compared with the most commonly used diagnostic criterion of occipitofrontal circumference (OFC) ≤ 10th. CONCLUSION: Age- and sex-adjusted brain volumes based on a large normative dataset may be useful predictors of functional outcomes and may identify a greater number of individuals with FASD than the currently used criterion of OFC.

Temporal discounting in children and adolescents with and without attention-deficit/hyperactivity disorder: a comparison of four scoring methods.

Temporal discounting (TD) tasks measure the preference for immediate rewards over larger delayed rewards and have been widely used to study impulsivity in children and adolescents with Attention-Deficit/Hyperactivity Disorder (ADHD). Relatively impulsive individuals tend to show high inconsistency in their choices, which makes it difficult to determine commonly used TD outcome measures (e.g., area under the curve, AUC). In this study, we leveraged two published datasets to compare four methods to compute TD outcome measures in children and adolescents (8-17 years) with (n = 107) and without ADHD (n = 128): two predetermined rules methods, a proportion method, and logistic regression. In both datasets, when using the two predetermined rules methods and the proportion method, TD outcomes were highly correlated and group differences in TD were similar. When using logistic regression, a large proportion of AUCs (95% in dataset 1; 33% in dataset 2) could not be computed due to inconsistent choice patterns. These findings indicate that predetermined rules methods (for studies with small sample sizes and experienced raters) and a proportion method (for studies with larger sample sizes or less experienced raters) are recommended over logistic regression when determining subjective reward values for participants with inconsistent choice patterns.

Early-Life Critical Windows of Susceptibility to Manganese Exposure and Sex-Specific Changes in Brain Connectivity in Late Adolescence.

Background: Early-life environmental exposures during critical windows (CWs) of development can impact life course health. Exposure to neuroactive metals such as manganese (Mn) during prenatal and early postnatal CWs may disrupt typical brain development, leading to persistent behavioral changes. Males and females may be differentially vulnerable to Mn, presenting distinctive CWs to Mn exposure. Methods: We used magnetic resonance imaging to investigate sex-specific associations between early-life Mn uptake and intrinsic functional connectivity in adolescence. A total of 71 participants (15-23 years old; 53% female) from the Public Health Impact of Manganese Exposure study completed a resting-state functional magnetic resonance imaging scan. We estimated dentine Mn concentrations at prenatal, postnatal, and early childhood periods using laser ablation-inductively coupled plasma-mass spectrometry. We performed seed-based correlation analyses to investigate the moderating effect of sex on the associations between Mn and intrinsic functional connectivity adjusting for age and socioeconomic status. Results: We identified significant sex-specific associations between dentine Mn at all time points and intrinsic functional connectivity in brain regions involved in cognitive and motor function: 1) prenatal: dorsal striatum, occipital/frontal lobes, and middle frontal gyrus; 2) postnatal: right putamen and cerebellum; and 3) early childhood: putamen and occipital, frontal, and temporal lobes. Network associations differed depending on exposure timing, suggesting that different brain networks may present distinctive CWs to Mn. Conclusions: These findings suggest that the developing brain is vulnerable to Mn exposure, with effects lasting through late adolescence, and that females and males are not equally vulnerable to these effects. Future studies should investigate cognitive and motor outcomes related to these associations.

Atypical developmental trajectories of white matter microstructure in prenatal alcohol exposure: Preliminary evidence from neurite orientation dispersion and density imaging.

Introduction: Fetal alcohol spectrum disorder (FASD), a life-long condition resulting from prenatal alcohol exposure (PAE), is associated with structural brain anomalies and neurobehavioral differences. Evidence from longitudinal neuroimaging suggest trajectories of white matter microstructure maturation are atypical in PAE. We aimed to further characterize longitudinal trajectories of developmental white matter microstructure change in children and adolescents with PAE compared to typically-developing Controls using diffusion-weighted Neurite Orientation Dispersion and Density Imaging (NODDI). Materials and methods: Participants: Youth with PAE (n = 34) and typically-developing Controls (n = 31) ages 8-17 years at enrollment. Participants underwent formal evaluation of growth and facial dysmorphology. Participants also completed two study visits (17 months apart on average), both of which involved cognitive testing and an MRI scan (data collected on a Siemens Prisma 3 T scanner). Age-related changes in the orientation dispersion index (ODI) and the neurite density index (NDI) were examined across five corpus callosum (CC) regions defined by tractography. Results: While linear trajectories suggested similar overall microstructural integrity in PAE and Controls, analyses of symmetrized percent change (SPC) indicated group differences in the timing and magnitude of age-related increases in ODI (indexing the bending and fanning of axons) in the central region of the CC, with PAE participants demonstrating atypically steep increases in dispersion with age compared to Controls. Participants with PAE also demonstrated greater increases in ODI in the mid posterior CC (trend-level group difference). In addition, SPC in ODI and NDI was differentially correlated with executive function performance for PAE participants and Controls, suggesting an atypical relationship between white matter microstructure maturation and cognitive function in PAE. Discussion: Preliminary findings suggest subtle atypicality in the timing and magnitude of age-related white matter microstructure maturation in PAE compared to typically-developing Controls. These findings add to the existing literature on neurodevelopmental trajectories in PAE and suggest that advanced biophysical diffusion modeling (NODDI) may be sensitive to biologically-meaningful microstructural changes in the CC that are disrupted by PAE. Findings of atypical brain maturation-behavior relationships in PAE highlight the need for further study. Further longitudinal research aimed at characterizing white matter neurodevelopmental trajectories in PAE will be important.

Delayed cortical thinning in children and adolescents with prenatal alcohol exposure.

BACKGROUND: Prenatal alcohol exposure (PAE) is associated with abnormalities in cortical structure and maturation, including cortical thickness (CT), cortical volume, and surface area. This study provides a longitudinal context for the developmental trajectory and timing of abnormal cortical maturation in PAE. METHODS: We studied 35 children with PAE and 30 nonexposed typically developing children (Comparisons), aged 8-17 at enrollment, who were recruited from the University of Minnesota FASD Program. Participants were matched on age and sex. They underwent a formal evaluation of growth and dysmorphic facial features associated with PAE and completed cognitive testing. MRI data were collected on a Siemens Prisma 3T scanner. Two sessions, each including MRI scans and cognitive testing, were spaced approximately 15 months apart on average. Change in CT and performance on tests of executive function (EF) were examined. RESULTS: Significant age-by-group (PAE vs. Comparison) linear interaction effects in CT were observed in the parietal, temporal, occipital, and insular cortices suggesting altered developmental trajectories in the PAE vs. Comparison groups. Results suggest a pattern of delayed cortical thinning in PAE, with the Comparison group showing more rapid thinning at younger ages and those with PAE showing accelerated thinning at older ages. Overall, children in the PAE group showed reduced cortical thinning across time relative to the Comparison participants. Symmetrized percent change (SPC) in CT in several regions was significantly correlated with EF performance at 15-month follow-up for the Comparison group but not the group with PAE. CONCLUSIONS: Regional differences were seen longitudinally in the trajectory and timing of CT change in children with PAE, suggesting delayed cortical maturation and an atypical pattern of development compared with typically developing individuals. In addition, exploratory correlation analyses of SPC and EF performance suggest the presence of atypical brain-behavior relationships in PAE. The findings highlight the potential role of altered developmental timing of cortical maturation in contributing to long-term functional impairment in PAE.

Temporal discounting for self and friends in adolescence: A fMRI study.

Adolescence is characterized by impulsivity but also by increased importance of friendships. This study took the novel perspective of testing temporal discounting in a fMRI task where choices could affect outcomes for 96 adolescents (aged 10-20-years) themselves and their best friend. Decisions either benefitted themselves (i.e., the Self Immediate - Self Delay' condition) or their friend (i.e., 'Friend Immediate - Friend Delay' condition); or juxtaposed rewards for themselves and their friends (i.e., the 'Self Immediate - Friend Delay' or 'Friend Immediate - Self Delay' conditions). We observed that younger adolescents were more impulsive; and all participants were more impulsive when this was associated with an immediate benefit for friends. Individual differences analyses revealed increased activity in the subgenual anterior cingulate cortex extending in the ventral striatum for immediate relative to delayed reward choices for self. Temporal choices were associated with activity in the prefrontal cortex, parietal cortex, insula, and ventral striatum, but only activity in the right inferior parietal lobe was associated with age. Finally, temporal delay choices for friends relative to self were associated with increased activity in the temporo-parietal junction and precuneus. Overall, this study shows a unique role of the social context in adolescents' temporal decision making.

Long-term follow-up of a randomized controlled trial of choline for neurodevelopment in fetal alcohol spectrum disorder: corpus callosum white matter microstructure and neurocognitive outcomes.

BACKGROUND: Fetal alcohol spectrum disorder (FASD) is a lifelong condition. Early interventions targeting core neurocognitive deficits have the potential to confer long-term neurodevelopmental benefits. Time-targeted choline supplementation is one such intervention that has been shown to provide neurodevelopmental benefits that emerge with age during childhood. We present a long-term follow-up study evaluating the neurodevelopmental effects of early choline supplementation in children with FASD approximately 7 years on average after an initial efficacy trial. METHODS: The initial study was a randomized, double-blind, placebo-controlled trial of choline vs. placebo in 2.5 to 5 year olds with FASD. Participants in this long-term follow-up study include 18 children (9 placebo; 9 choline) seen 7 years on average following initial trial completion. The mean age at follow-up was 11.0 years old. Diagnoses were 28% fetal alcohol syndrome (FAS), 28% partial FAS, and 44% alcohol-related neurodevelopmental disorder. The follow-up included measures of executive functioning and an MRI scan. RESULTS: Children who received choline had better performance on several tasks of lower-order executive function (e.g., processing speed) and showed higher white matter microstructure organization (i.e., greater axon coherence) in the splenium of the corpus callosum compared to the placebo group. CONCLUSIONS: These preliminary findings, although exploratory at this stage, highlight potential long-term benefits of choline as a neurodevelopmental intervention for FASD and suggest that choline may affect white matter development, representing a potential target of choline in this population. TRIAL REGISTRATION: Prior to enrollment, this trial was registered with clinicaltrials.gov ( NCT01149538 ) on June 23, 2010.

Prenatal and Postnatal Choline Supplementation in Fetal Alcohol Spectrum Disorder.

Fetal alcohol spectrum disorder (FASD) is common and represents a significant public health burden, yet very few interventions have been tested in FASD. Cognitive deficits are core features of FASD, ranging from broad intellectual impairment to selective problems in attention, executive functioning, memory, visual-perceptual/motor skills, social cognition, and academics. One potential intervention for the cognitive impairments associated with FASD is the essential nutrient choline, which is known to have numerous direct effects on brain and cognition in both typical and atypical development. We provide a summary of the literature supporting the use of choline as a neurodevelopmental intervention in those affected by prenatal alcohol. We first discuss how alcohol interferes with normal brain development. We then provide a comprehensive overview of the nutrient choline and discuss its role in typical brain development and its application in the optimization of brain development following early insult. Next, we review the preclinical literature that provides evidence of choline's potential as an intervention following alcohol exposure. Then, we review a handful of existing human studies of choline supplementation in FASD. Lastly, we conclude with a review of practical considerations in choline supplementation, including dose, formulation, and feasibility in children.

Peer feedback decreases impulsive choice in adolescents with and without attention-deficit/hyperactivity disorder.

Background: Impulsivity is a core feature of attention-deficit/hyperactivity disorder (ADHD). Previous work using the delay discounting task to assess impulsivity reveals that adolescents with ADHD tend to prefer a smaller-immediate reward over a larger-delayed reward, and this relates to problematic choices in daily life. To gain a better understanding of daily decision-making in adolescence, it is important to examine the social context, as peers have a major influence on decisions. Peer influence often has a negative connotation, but also provides an opportunity to promote positive outcomes. To date, it is unclear if peers affect impulsive decision-making in adolescents with ADHD, for better or for worse. Methods: The aim of this preregistered study was to examine the effect of peer feedback on impulsive choice in male adolescents with and without ADHD (ages 13-23; N = 113). We utilized an adapted delay discounting task that was administered alone, in a social condition, and alone again. In the social condition, adolescents received either (between-subjects) manipulated impulsive or non-impulsive peer feedback. Impulsive peer feedback consisted of likes for choosing the smaller immediate reward, whereas non-impulsive peers endorsed choosing the larger delayed reward. Results: Preregistered analyses showed that non-impulsive peer feedback resulted in decreased impulsive choice, whereas impulsive peer feedback did not alter decision-making in adolescents with and without ADHD. Explorative analyses of inattention and hyperactivity-impulsivity symptoms in the total sample, irrespective of diagnosis, showed that lower hyperactivity-impulsivity and more inattention symptoms were associated with increased susceptibility to non-impulsive peer feedback. Conclusions: Together, these findings indicate that peers may provide an opportunity to decrease impulsivity and emphasize individual differences in susceptibility to non-impulsive peer feedback related to inattention and hyperactivity-impulsivity. Therefore, peer feedback may be a promising component in behavioral peer-supported interventions in adolescents with ADHD.

Prenatal metal mixture concentrations and reward motivation in children.

Reward motivation is a complex umbrella term encompassing the cognitions, emotions, and behaviors involved in the activation, execution, and persistence of goal-directed behavior. Altered reward motivation in children is characteristic of many neurodevelopmental and psychiatric disorders. Previously difficult to operationalize, the Progressive Ratio (PR) task has been widely used to assess reward motivation in animal and human studies, including children. Because the neural circuitry supporting reward motivation starts developing during pregnancy, and is sensitive to disruption by environmental toxicants, including metals, the goal of this study was to examine the association between prenatal concentrations of a mixture of neurotoxic metals and reward motivation in children. We measured reward motivation by administering a PR test to 373 children ages 6-8 years enrolled in the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) Study in Mexico City. Children were asked to press a response lever for a token reward; one press on the response lever was required to earn the first token and each subsequent token required an additional 10 lever presses. Maternal blood concentrations of lead, manganese, zinc, arsenic, cadmium, and selenium were measured using inductively-coupled plasma mass spectrometry during the 2nd and 3rd trimesters of pregnancy. We performed generalized Weighted Quantile Sum (gWQS) regression analyses to examine associations between the prenatal metal mixture and reward motivation; adjusting for child sex, birthweight and age; and maternal IQ, education, and socioeconomic status. The prenatal metal mixture was significantly associated with higher motivation as indicated by more lever presses (ß = 0.02, p < 0.001) and a shorter time between receiving the reinforcer and the first press (ß = 0.23, p = 0.01), and between subsequent presses (ß = 0.07, p = 0.005). Contributions of different metals to this association differed by trimester and child sex. These findings suggest that children with increased exposure to metal during the 2nd and 3rd trimesters of gestation demonstrate increased reward motivation, which may reflect a tendency to perseverate or hypersensitivity to positive reinforcement.

Impulsive and risky decision-making in adolescents with attention-deficit/hyperactivity disorder (ADHD): The need for a developmental perspective.

Impulsive and risky decision-making peaks in adolescence, and is consistently associated with the neurodevelopmental disorder Attention-Deficit/Hyperactivity Disorder (ADHD), regardless of age. In this brief review, we demonstrate the similarity of theoretical models explaining impulsive and risky decision-making that originate in two relatively distinct literatures (i.e., on adolescence and on ADHD). We summarize research thus far and conclude that the presence of ADHD during adolescence further exacerbates the tendency that is already present in adolescents to make impulsive and risky decisions. We also conclude that much is still unknown about the developmental trajectories of individuals with ADHD with regard to impulsive and risky decision making, and we therefore provide several hypotheses that warrant further longitudinal research.

Prenatal PM2.5 exposure in the second and third trimesters predicts neurocognitive performance at age 9-10 years: A cohort study of Mexico City children.

INTRODUCTION: Prenatal exposure to fine particulate matter air pollution (PM2.5) is an important, under-studied risk factor for neurodevelopmental dysfunction. We describe the relationships between prenatal PM2.5 exposure and vigilance and inhibitory control, executive functions related to multiple health outcomes in Mexico City children. METHODS: We studied 320 children enrolled in Programming Research in Obesity, GRowth, Environment and Social Stressors, a longitudinal birth cohort study in Mexico City. We used a spatio-temporal model to estimate daily prenatal PM2.5 exposure at each participant's residential address. At age 9-10 years, children performed three Go/No-Go tasks, which measure vigilance and inhibitory control ability. We used Latent class analysis (LCA) to classify performance into subgroups that reflected neurocognitive performance and applied multivariate regression and distributed lag regression modeling (DLM) to test overall and time-dependent associations between prenatal PM2.5 exposure and Go/No-Go performance. RESULTS: LCA detected two Go/No-Go phenotypes: high performers (Class 1) and low performers (Class 2). Predicting odds of Class 1 vs Class 2 membership based on prenatal PM2.5 exposure timing, logistic regression modeling showed that average prenatal PM2.5 exposure in the second and third trimesters correlated with increased odds of membership in low-performance Class 2 (OR = 1.59 (1.16, 2.17), p = 0.004). Additionally, DLM analysis identified a critical window consisting of gestational days 103-268 (second and third trimesters) in which prenatal PM2.5 exposure predicted poorer Go/No-Go performance. DISCUSSION: Increased prenatal PM2.5 exposure predicted decreased vigilance and inhibitory control at age 9-10 years. These findings highlight the second and third trimesters of gestation as critical windows of PM2.5 exposure for the development of vigilance and inhibitory control in preadolescent children. Because childhood development of vigilance and inhibitory control informs behavior, academic performance, and self-regulation into adulthood, these results may help to describe the relationship of prenatal PM2.5 exposure to long-term health and psychosocial outcomes. The integrative methodology of this study also contributes to a shift towards more holistic analysis.

Prenatal urinary concentrations of phthalate metabolites and behavioral problems in Mexican children: The Programming Research in Obesity, Growth Environment and Social Stress (PROGRESS) study.

BACKGROUND: Phthalate exposure has been associated with increased childhood behavioral problems. Existing studies failed to include phthalate replacements and did not account for high correlations among phthalates. Phthalates' exposure is higher in Mexico than in U.S. locations, making it an ideal target population for this study. AIM: To examine associations between 15 maternal prenatal phthalate metabolite concentrations and children's behavioral problems. METHODS: We quantified phthalate metabolites in maternal urine samples from maternal-child dyads (n = 514) enrolled in the Programming Research in Obesity, Growth Environment and Social Stress (PROGRESS) birth cohort in Mexico City. We performed least absolute shrinkage and selection operator (LASSO) regressions to identify associations between specific-gravity adjusted log2-transformed phthalate metabolites and parent-reported 4-6 year old behavior on the Behavior Assessment System for Children (BASC-2), accounting for metabolite correlations. We adjusted for socio-demographic and birth-related factors, and examined associations stratified by sex. RESULTS: Higher prenatal mono-2-ethyl-5-carboxypentyl terephthalate (MECPTP) urinary concentrations were associated with increased hyperactivity scores in the overall sample (ß = 0.57, 95% CI = 0.17, 1.13) and in girls (ß = 0.54, 95% CI = 0.16, 1.08), overall behavioral problems in boys (ß = 0.58, 95% CI = 0.20, 1.15), and depression scores in boys (ß = 0.44, 95% CI = 0.06, 0.88). Higher prenatal monobenzyl phthalate (MBzP) concentrations were associated with reduced hyperactivity scores in girls (ß = -0.54, 95% CI = -1.08, -0.21). DISCUSSION: Our findings suggested that prenatal concentrations of phthalates and their replacements altered child neurodevelopment and those associations may be influenced sex.

Social behaviors and gray matter volumes of brain areas supporting social cognition in children and adolescents with prenatal alcohol exposure.

The goal of this study was to examine: 1) differences in parent-reported prosocial and antisocial behaviors between children and adolescents with and without prenatal alcohol exposure (PAE); 2) differences in gray matter volumes of brain areas supporting social cognition between children and adolescents with and without PAE; 3) correlations between gray matter volumes of brain areas supporting social cognition and parent-reported prosocial and antisocial behaviors. Parents of children and adolescents ages 8-16 years completed measures on their prosocial and antisocial behaviors (i.e., Behavior Assessment Scale for Children, Vineland Adaptive Behaviors Scales, and Child Behavior Checklist) (n = 84; 41 with PAE, 43 without PAE). Seventy-nine participants (40 with PAE, 39 without PAE) also completed a structural Magnetic Resonance Imaging (MRI) scan with quality data. Gray matter volumes of seven brain areas supporting social cognitive processes were computed using automated procedures (FreeSurfer 6.0): bilateral fusiform gyrus, superior temporal gyrus, medial orbitofrontal cortex, lateral orbitofrontal cortex, posterior cingulate cortex, precuneus, and temporal pole. Children and adolescents with PAE showed decreased prosocial behaviors and increased antisocial behaviors as well as smaller volumes of the precuneus and lateral orbitofrontal cortex, even when controlling for total intracranial volume. Social brain volumes were not significantly correlated with prosocial or antisocial behaviors. These findings suggest that children and adolescents with PAE show worse social functioning and smaller volumes of brain areas supporting self-awareness, perspective-taking and emotion-regulation than their same-age peers without PAE.

Early delay of gratification predicts later inhibitory control and academic performance in children with prenatal alcohol exposure.

Fetal alcohol spectrum disorder (FASD) affects 2-5% of the children in the United States. In the preschool age-range, inhibitory deficits frequently manifest as impaired ability to delay gratification, which is associated with deficits in cognitive flexibility in these children. The goal of this longitudinal study was to determine whether the ability to delay gratification in preschool children with FASD is (1) associated with broader manifestations in temperament and behavior; (2) predictive of later inhibitory control, cognitive flexibility and working memory in middle childhood; and (3) predictive of later parent-reported behavioral problems and school functioning in middle childhood. Forty-seven children with FASD, ages 2.5-5 years were administered a delay of gratification task in which they chose between receiving 2 snacks immediately or 10 snacks after waiting for 10 min. Two groups were defined based on a median split of waiting time. Four years later, 29 children completed measures of inhibitory control (Flanker task), cognitive flexibility (Dimensional Change Card Sort Test), and working memory (Stanford-Binet Intelligence Scales), and their parents completed the Child Behavior Checklist as a measure of the child's behavioral problems and school functioning. Children with longer wait times on the delay of gratification task in preschool showed better inhibitory control on the Flanker task in middle childhood and better parent-reported school functioning in English. These findings indicate that early inhibitory capacity persists into middle childhood in those with FASD, and may be a promising target for early intervention to improve later cognitive outcomes in these children.

Hippocampal subfield abnormalities and memory functioning in children with fetal alcohol Spectrum disorders.

BACKGROUND: Prenatal alcohol exposure (PAE) affects early brain development and has been associated with hippocampal damage. Animal models of PAE have suggested that some subfields of the hippocampus may be more susceptible to damage than others. Recent advances in structural MRI processing now allow us to examine the morphology of hippocampal subfields in humans with PAE. METHOD: Structural MRI scans were collected from 40 children with PAE and 39 typically developing children (ages 8-16). The images were processed using the Human Connectome Project Minimal Preprocessing Pipeline (v4.0.1) and the Hippocampal Subfields package (v21) from FreeSurfer. Using a large dataset of typically developing children enrolled in the Human Connectome Project in Development (HCP-D) for normative standards, we computed age-specific volumetric z-scores for our two samples. Using these norm-adjusted hippocampal subfield volumes, comparisons were performed between children with PAE and typically developing children, controlling for total intracranial volume. Lastly, we investigated whether subfield volumes correlated with episodic memory (i.e., Picture Sequence Memory test of the NIH toolbox). RESULTS: Five subfields had significantly smaller adjusted volumes in children with PAE than in typically developing controls: CA1, CA4, subiculum, presubiculum, and the hippocampal tail. Subfield volumes were not significantly correlated with episodic memory. CONCLUSIONS: The results suggest that several regions of the hippocampus may be particularly affected by PAE. The finding of smaller CA1 volumes parallels previous reports in rodent models. The novel findings of decreased volume in the subicular cortex, CA4 and the hippocampal tail suggest avenues for future research.

Executive and Social Functioning Across Development in Children and Adolescents With Prenatal Alcohol Exposure.

BACKGROUND: Prenatal alcohol exposure (PAE) is linked to a variety of neurodevelopmental challenges, including social functioning (SF) and executive functioning (EF) deficits. These deficits present differently across developmental stages from preschool age to adolescence. METHODS: The post hoc analyses described here were conducted on data from 83 preschool-age children with PAE (early childhood group; ages 2.5 to 5.0) and 95 adolescents (49 with PAE, 46 controls; ages 8 to 16). Each child completed EF tasks as part of several prior studies. Parents completed social and communication inventories about their child's abilities. Thirty-three participants from the early childhood group returned for a 4-year follow-up and completed both SF and EF measures. RESULTS: Both the early childhood and adolescent groups with PAE showed deficits in SF and EF. There was a relationship between SF and EF within the adolescent PAE group that was not present in the adolescent control group or the early childhood PAE group. However, at the 4-year follow-up (Mage  = 8.45), participants originally in the early childhood PAE group also demonstrated this relationship. CONCLUSIONS: These findings support previous research on EF/SF deficits in adolescents with PAE while also addressing a gap in the literature concerning early childhood research on this topic. Additionally, these findings suggest that the relationship between EF and SF deficits may strengthen throughout development. This line of research highlights potential sensitive periods for SF and EF training in children with PAE and suggests that fetal alcohol spectrum disorders programs consider targeting EF training as a component of social skill interventions.

Five-year-olds' facial mimicry following social ostracism is modulated by attachment security.

Social ostracism triggers an increase in affiliative behaviours. One such behaviour is the rapid copying of others' facial expressions, called facial mimicry. Insofar, it remains unknown how individual differences in intrinsic affiliation motivation regulate responses to social ostracism during early development. We examined children's facial mimicry following ostracism as modulated by individual differences in the affiliation motivation, expressed in their attachment tendencies. Resistant and avoidant tendencies are characterized by high and low affiliation motivation, and were hypothesized to lead to facial mimicry enhancement or suppression towards an ostracizing partner, respectively. Following an ostracism manipulation in which children played a virtual game (Cyberball) with an includer and an excluder peer, mimicry of the two peers' happy and sad facial expressions was recorded with electromyography (EMG). Attachment was assessed via parent-report questionnaire. We found that 5-year-olds smiled to sad facial expressions of the excluder peer, while they showed no facial reactions for the includer peer. Neither resistant nor avoidant tendencies predicted facial mimicry to the excluder peer. Yet, securely attached children smiled towards the excluder peer, when sad facial expressions were displayed. In conclusion, these findings suggest a modulation of facial reactions following ostracism by early attachment.