Associations between EEG trajectories, family income, and cognitive abilities over the first two years of life.

We sought to characterize developmental trajectories of EEG spectral power over the first 2 years after birth and examine whether family income or maternal education alter those trajectories. We analyzed EEGs (n = 161 infants, 534 EEGs) collected longitudinally between 2 and 24 months of age, and calculated frontal absolute power across 7 canonical frequency bands. For each frequency band, a piecewise growth curve model was fit, resulting in an estimated intercept and two slope parameters from 2 to 9 months and 9-24 months of age. Across 6/7 frequency bands, absolute power significantly increased over age, with steeper slopes in the 2-9 month period compared to 9-24 months. Increased family income, but not maternal education, was associated with higher intercept (2-3 month power) across delta-gamma bands (p range = 0.002-0.04), and reduced change in power between 2 and 9 months of age in lower frequency bands (delta-alpha, p range = 0.01-0.02). There was no significant effect of income on slope between 9 and 24 months. EEG intercept and slope measures did not mediate relationships between income and 24-month verbal and nonverbal development. These results add to growing literature concerning the role of socioeconomic factors in shaping brain trajectories.

Associations of socioeconomic and other environmental factors with early brain development in Bangladeshi infants and children.

Studies of infants growing up in high-income countries reveal developmental changes in electroencephalography (EEG) power whereby socioeconomic factors - specifically, low SES and low income - are associated with lower EEG power in infants aged newborn to nine months. In the current paper we explore relationships of spectral EEG power across three regions (frontal, central, and parietal) and four frequency bands (theta, alpha, beta, and gamma) with socioeconomic and psychosocial factors in a cohort of n = 160 6-month-old infants and n = 187 36-month-old children living in Dhaka, Bangladesh. Household wealth is assessed as a multi-dimensional composite score encompassing income, assets, and housing materials. Psychosocial factors include maternal perceived stress and family caregiving activities. Among the 6-month-old infants we do not observe any association of household wealth or psychosocial factors with EEG power. Among the 36-month-old children, we find that household wealth is negatively associated absolute power in the beta and gamma bands across frontal, central, and parietal electrodes. We also find that higher reports of maternal perceived stress are associated with more absolute theta power in frontal and central regions in the 36-month-old children. The finding of a negative relationship of household wealth with beta and gamma power in 36-month-old children differs from findings previously observed in infants in high-income countries. Overall, findings suggest that children's environment continues to influence the development of EEG oscillations and provide support for the utility of EEG to quantify developmental effects of early life experiences on neural functional outcomes in low income countries.

Socioeconomic and psychological correlates of postpartum depression at 6 months in Dhaka, Bangladesh.

To current study aimed to estimate the point prevalence and identify correlates of postpartum depression (PPD) in a sample of mothers in Dhaka. A total of 235 participants from low- and middle-SES neighbourhoods in Dhaka completed the Edinburgh Postnatal Depression Scale (EPDS) and other assessments of socioeconomic and psychological factors at 24 weeks postpartum. Regression models were fit to explore potential correlates of PPD. The estimated prevalence of high PPD risk in the current sample is 24.3%. In multivariable linear regression models, recent life events, perceived stress and household resources (e.g., access to cooking gas, telephone, furniture, electricity, television, etc.) were significantly associated with PPD. The association of social support with PPD when controlling for other variables was sensitive to the choice of social support measure, highlighting an important methodological issue. The point prevalence of PPD among poor, urban mothers in Bangladesh ranges from 12.3 to 28.5%, with psychological risk factors and household resources as strong correlates.

Relating anthropometric indicators to brain structure in 2-month-old Bangladeshi infants growing up in poverty: A pilot study.

Anthropometric indicators, including stunting, underweight, and wasting, have previously been associated with poor neurocognitive outcomes. This link may exist because malnutrition and infection, which are known to affect height and weight, also impact brain structure according to animal models. However, a relationship between anthropometric indicators and brain structural measures has not been tested yet, perhaps because stunting, underweight, and wasting are uncommon in higher-resource settings. Further, with diminished anthropometric growth prevalent in low-resource settings, where biological and psychosocial hazards are most severe, one might expect additional links between measures of poverty, anthropometry, and brain structure. To begin to examine these relationships, we conducted an MRI study in 2-3-month-old infants growing up in the extremely impoverished urban setting of Dhaka, Bangladesh. The sample size was relatively small because the challenges of investigating infant brain structure in a low-resource setting needed to be realized and resolved before introducing a larger cohort. Initially, fifty-four infants underwent T1 sequences using 3T MRI, and resulting structural images were segmented into gray and white matter maps, which were carefully evaluated for accurate tissue labeling by a pediatric neuroradiologist. Gray and white matter volumes from 29 infants (79 â€‹± â€‹10 days-of-age; F/M â€‹= â€‹12/17), whose segmentations were of relatively high quality, were submitted to semi-partial correlation analyses with stunting, underweight, and wasting, which were measured using height-for-age (HAZ), weight-for-age (WAZ), and weight-for-height (WHZ) scores. Positive semi-partial correlations (after adjusting for chronological age and sex and correcting for multiple comparisons) were observed between white matter volume and HAZ and WAZ; however, WHZ was not correlated with any measure of brain volume. No associations were observed between income-to-needs or maternal education and brain volumetric measures, suggesting that measures of poverty were not associated with total brain tissue volume in this sample. Overall, these results provide the first link between diminished anthropometric growth and white matter volume in infancy. Challenges of conducting a developmental neuroimaging study in a low-resource country are also described.

Introduction to special issue on global child development studies.

As global child development research is taking off, this special issue provides a collection of recent research characterizing child development across the globe, validating behavioral and neuroimaging tools across diverse geographical setting and cultures, exploring relationships between risk and protective factors and diverse child outcomes, and testing novel avenues of innovative intervention. In particular, three prominent themes that emerge from this special issue are (a) research linking biology and behavior in the service of uncovering biological systems that are susceptible to experience and may mediate associations between experiences and long-term developmental outcomes in global child development research, (b) a movement towards inclusion of more detailed investigation of children's socio-emotional functions in global child development research, and (c) longitudinal studies of developmental outcomes across global settings. In this introduction we outline key themes and findings from the 25 articles included in the special issue.

Role of maternal health and infant inflammation in nutritional and neurodevelopmental outcomes of two-year-old Bangladeshi children.

BACKGROUND: Previous studies have shown maternal, inflammatory, and socioeconomic variables to be associated with growth and neurodevelopment in children from low-income countries. However, these outcomes are multifactorial and work describing which predictors most strongly influence them is lacking. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a longitudinal study of Bangladeshi children from birth to two years to assess oral vaccine efficacy. Variables pertaining to maternal and perinatal health, socioeconomic status, early childhood enteric and systemic inflammation, and anthropometry were collected. Bayley-III neurodevelopmental assessment was conducted at two years. As a secondary analysis, we employed hierarchical cluster and random forests techniques to identify and rank which variables predicted growth and neurodevelopment. Cluster analysis demonstrated three distinct groups of predictors. Mother's weight and length-for-age Z score (LAZ) at enrollment were the strongest predictors of LAZ at two years. Cognitive score on Bayley-III was strongly predicted by weight-for-age (WAZ) at enrollment, income, and LAZ at enrollment. Top predictors of language included Rotavirus vaccination, plasma IL 5, sCD14, TNFα, mother's weight, and male gender. Motor function was best predicted by fecal calprotectin, WAZ at enrollment, fecal neopterin, and plasma CRP index. The strongest predictors for social-emotional score included plasma sCD14, income, WAZ at enrollment, and LAZ at enrollment. Based on the random forests' predictions, the estimated percentage of variation explained was 35.4% for LAZ at two years, 34.3% for ΔLAZ, 42.7% for cognitive score, 28.1% for language, 40.8% for motor, and 37.9% for social-emotional score. CONCLUSIONS/SIGNIFICANCE: Birth anthropometry and maternal weight were strong predictors of growth while enteric and systemic inflammation had stronger associations with neurodevelopment. Birth anthropometry was a powerful predictor for all outcomes. These data suggest that further study of stunting in low-income settings should include variables relating to maternal and prenatal health, while investigations focusing on neurodevelopmental outcomes should additionally target causes of systemic and enteric inflammation.

Placebo-controlled crossover assessment of mecasermin for the treatment of Rett syndrome.

Objective: To measure the efficacy of mecasermin (recombinant human insulin-like growth factor 1, rhIGF-1), for treating symptoms of Rett syndrome (RTT) in a pediatric population using a double-blind crossover study design. Methods: Thirty girls with classic RTT in postregression stage were randomly assigned to placebo or rhIGF-1 in treatment period 1 and crossed over to the opposite assignment for period 2 (both 20 weeks), separated by a 28-week washout period. The primary endpoints were as follows: Anxiety Depression and Mood Scale (ADAMS) Social Avoidance subscale, Rett Syndrome Behaviour Questionnaire (RSBQ) Fear/Anxiety subscale, Parent Target Symptom Visual Analog Scale (PTSVAS) top three concerns, Clinical Global Impression (CGI), Parent Global Impression (PGI), and the Kerr severity scale. Cardiorespiratory- and electroencephalography (EEG)-based biomarkers were also analyzed. Results: There were no significant differences between randomization groups. The majority of AEs were mild to moderate, although 12 episodes of serious AEs occurred. The Kerr severity scale, ADAMS Depressed Mood subscale, Visual Analog Scale Hyperventilation, and delta average power change scores significantly increased, implying worsening of symptoms. Electroencephalography (EEG) parameters also deteriorated. A secondary analysis of subjects who were not involved in a placebo recall confirmed most of these findings. However, it also revealed improvements on a measure of stereotypic behavior and another of social communication. Interpretation: As in the phase 1 trial, rhIGF-1 was safe; however, the drug did not reveal significant improvement, and some parameters worsened.

Neurodevelopment: The Impact of Nutrition and Inflammation During Early to Middle Childhood in Low-Resource Settings.

The early to middle childhood years are a critical period for child neurodevelopment. Nutritional deficiencies, infection, and inflammation are major contributors to impaired child neurodevelopment in these years, particularly in low-resource settings. This review identifies global research priorities relating to nutrition, infection, and inflammation in early to middle childhood neurodevelopment. The research priority areas identified include: (1) assessment of how nutrition, infection, or inflammation in the preconception, prenatal, and infancy periods (or interventions in these periods) affect function in early to middle childhood; (2) assessment of whether effects of nutritional interventions vary by poverty or inflammation; (3) determination of the feasibility of preschool- and school-based integrated nutritional interventions; (4) improved assessment of the epidemiology of infection- and inflammation-related neurodevelopmental impairment (NDI); (5) identification of mechanisms through which infection causes NDI; (6) identification of noninfectious causes of inflammation-related NDI and interventions for causes already identified (eg, environmental factors); and (7) studies on the effects of interactions between nutritional, infectious, and inflammatory factors on neurodevelopment in early to middle childhood. Areas of emerging importance that require additional study include the effects of maternal Zika virus infection, childhood environmental enteropathy, and alterations in the child's microbiome on neurodevelopment in early to middle childhood. Research in these key areas will be critical to the development of interventions to optimize the neurodevelopmental potential of children worldwide in the early to middle childhood years.

Assessment of Neurodevelopment, Nutrition, and Inflammation From Fetal Life to Adolescence in Low-Resource Settings.

Efforts to improve child neurodevelopment are critical to health, equity, and sustainable development, particularly in low-resource settings in the United States and globally. The colliding epidemics of food insecurity, infectious diseases, and noncommunicable diseases interact and impact neurodevelopment. Understanding the complex relationships between nutrition, inflammation, and neurodevelopment can inform clinical and public health interventions to improve outcomes. This article reviews key definitions, tools, and considerations for the assessment of nutrition, inflammation, and child neurodevelopment. The effectiveness of existing assessment tools to reflect status and biology, particularly in relation to each other, and to predict long-term changes in health is examined. The aim of this review is to present the extant evidence, identify critical research gaps, and suggest a research agenda for future longitudinal and intervention studies to address the assessment of nutrition, inflammation, and child neurodevelopment, particularly in low-resource settings. Despite research gaps, there is a strong relationship between nutrition, inflammation, environmental factors, and child neurodevelopment, which emphasizes the need to evaluate targeted, early interventions to improve long-term health and well-being.

Gamma power in rural Pakistani children: Links to executive function and verbal ability.

Children in low- and middle-income countries are at high risk of cognitive deficits due to environmental deprivation that compromises brain development. Despite the high prevalence of unrealized cognitive potential, very little is known about neural correlates of cognition in this population. We assessed resting EEG power and cognitive ability in 105 highly disadvantaged 48-month-old children in rural Pakistan. An increase in EEG power in gamma frequency bands (21-30Hz and 31-45Hz) was associated with better executive function. For girls, EEG gamma power also related to higher verbal IQ. This study identifies EEG gamma power as a neural marker of cognitive function in disadvantaged children in low- and middle-income countries. Elevated gamma power may be a particularly important protective factor for girls, who may experience greater deprivation due to gender inequality.

Socioeconomic disadvantage and neural development from infancy through early childhood.

BACKGROUND: Early social experiences are believed to shape neurodevelopment, with potentially lifelong consequences. Yet minimal evidence exists regarding the role of the social environment on children's neural functioning, a core domain of neurodevelopment. METHODS: We analysed data from 36 443 participants in the United States Collaborative Perinatal Project, a socioeconomically diverse pregnancy cohort conducted between 1959 and 1974. Study outcomes included: physician (neurologist or paediatrician)-rated neurological abnormality neonatally and thereafter at 4 months and 1 and 7 years; indicators of neurological hard signs and soft signs; and indicators of autonomic nervous system function. RESULTS: Children born to socioeconomically disadvantaged parents were more likely to exhibit neurological abnormalities at 4 months [odds ratio (OR) = 1.20; 95% confidence interval (CI) = 1.06, 1.37], 1 year (OR = 1.35; CI = 1.17, 1.56), and 7 years (OR = 1.67; CI = 1.48, 1.89), and more likely to exhibit neurological hard signs (OR = 1.39; CI = 1.10, 1.76), soft signs (OR = 1.26; CI = 1.09, 1.45) and autonomic nervous system dysfunctions at 7 years. Pregnancy and delivery complications, themselves associated with socioeconomic disadvantage, did not account for the higher risks of neurological abnormalities among disadvantaged children. CONCLUSIONS: Parental socioeconomic disadvantage was, independently from pregnancy and delivery complications, associated with abnormal child neural development during the first 7 years of life. These findings reinforce the importance of the early environment for neurodevelopment generally, and expand knowledge regarding the domains of neurodevelopment affected by environmental conditions. Further work is needed to determine the mechanisms linking socioeconomic disadvantage with children's neural functioning, the timing of such mechanisms and their potential reversibility.

Safety, pharmacokinetics, and preliminary assessment of efficacy of mecasermin (recombinant human IGF-1) for the treatment of Rett syndrome.

Rett syndrome (RTT) is a severe X-linked neurodevelopmental disorder mainly affecting females and is associated with mutations in MECP2, the gene encoding methyl CpG-binding protein 2. Mouse models suggest that recombinant human insulin-like growth factor 1 (IGF-1) (rhIGF1) (mecasermin) may improve many clinical features. We evaluated the safety, tolerability, and pharmacokinetic profiles of IGF-1 in 12 girls with MECP2 mutations (9 with RTT). In addition, we performed a preliminary assessment of efficacy using automated cardiorespiratory measures, EEG, a set of RTT-oriented clinical assessments, and two standardized behavioral questionnaires. This phase 1 trial included a 4-wk multiple ascending dose (MAD) (40-120 µg/kg twice daily) period and a 20-wk open-label extension (OLE) at the maximum dose. Twelve subjects completed the MAD and 10 the entire study, without evidence of hypoglycemia or serious adverse events. Mecasermin reached the CNS compartment as evidenced by the increase in cerebrospinal fluid IGF-1 levels at the end of the MAD. The drug followed nonlinear kinetics, with greater distribution in the peripheral compartment. Cardiorespiratory measures showed that apnea improved during the OLE. Some neurobehavioral parameters, specifically measures of anxiety and mood also improved during the OLE. These improvements in mood and anxiety scores were supported by reversal of right frontal alpha band asymmetry on EEG, an index of anxiety and depression. Our data indicate that IGF-1 is safe and well tolerated in girls with RTT and, as demonstrated in preclinical studies, ameliorates certain breathing and behavioral abnormalities.

What are the links between maternal social status, hippocampal function, and HPA axis function in children?

The association of parental social status with multiple health and achievement indicators in adulthood has driven researchers to attempt to identify mechanisms by which social experience in childhood could shift developmental trajectories. Some accounts for observed linkages between parental social status in childhood and health have hypothesized that early stress exposure could result in chronic disruptions in hypothalamic-pituitary-adrenal (HPA) axis activation, and that this activation could lead to long-term changes. A robust literature in adult animals has demonstrated that chronic HPA axis activation leads to changes in hippocampal structure and function. In the current study, consistent with studies in animals, we observe an association between both maternal self-rated social status and hippocampal activation in children and between maternal self-rated social status and salivary cortisol in children.

Inequality in early childhood: risk and protective factors for early child development.

Inequality between and within populations has origins in adverse early experiences. Developmental neuroscience shows how early biological and psychosocial experiences affect brain development. We previously identified inadequate cognitive stimulation, stunting, iodine deficiency, and iron-deficiency anaemia as key risks that prevent millions of young children from attaining their developmental potential. Recent research emphasises the importance of these risks, strengthens the evidence for other risk factors including intrauterine growth restriction, malaria, lead exposure, HIV infection, maternal depression, institutionalisation, and exposure to societal violence, and identifies protective factors such as breastfeeding and maternal education. Evidence on risks resulting from prenatal maternal nutrition, maternal stress, and families affected with HIV is emerging. Interventions are urgently needed to reduce children's risk exposure and to promote development in affected children. Our goal is to provide information to help the setting of priorities for early child development programmes and policies to benefit the world's poorest children and reduce persistent inequalities.

Near-infrared spectroscopy: a report from the McDonnell infant methodology consortium.

Near-infrared spectroscopy (NIRS) is a new and increasingly widespread brain imaging technique, particularly suitable for young infants. The laboratories of the McDonnell Consortium have contributed to the technological development and research applications of this technique for nearly a decade. The present paper provides a general introduction to the technique as well as a detailed report of the methodological innovations developed by the Consortium. The basic principles of NIRS and some of the existing developmental studies are reviewed. Issues concerning technological improvements, parameter optimization, possible experimental designs and data analysis techniques are discussed and illustrated by novel empirical data.

Incidental findings in magnetic resonance imaging (MRI) brain research.

The use of magnetic resonance imaging (MRI) to investigate brain structure ("structural MRI") and function (so-called "functional MRI") has become increasingly common among neuroscientists, psychologists, and even economists in recent years. Yet, despite this increase in use, relatively little attention has been paid to the issue of incidental findings. The current paper discusses these issues, and anticipates the future of incidental findings in the context of other neuroimaging tools currently being used to investigate the living brain.

Development and natural history of mood disorders.

To expand and accelerate research on mood disorders, the National Institute of Mental Health (NIMH) developed a project to formulate a strategic research plan for mood disorder research. One of the areas selected for review concerns the development and natural history of these disorders. The NIMH convened a multidisciplinary Workgroup of scientists to review the field and the NIMH portfolio and to generate specific recommendations. To encourage a balanced and creative set of proposals, experts were included within and outside this area of research, as well as public stakeholders. The Workgroup identified the need for expanded knowledge of mood disorders in children and adolescents, noting important gaps in understanding the onset, course, and recurrence of early-onset unipolar and bipolar disorder. Recommendations included the need for a multidisciplinary research initiative on the pathogenesis of unipolar depression encompassing genetic and environmental risk and protective factors. Specifically, we encourage the NIMH to convene a panel of experts and advocates to review the findings concerning children at high risk for unipolar depression. Joint analyses of existing data sets should examine specific risk factors to refine models of pathogenesis in preparation for the next era of multidisciplinary research. Other priority areas include the need to assess the long-term impact of successful treatment of juvenile depression and known precursors of depression, in particular, childhood anxiety disorders. Expanded knowledge of pediatric-onset bipolar disorder was identified as a particularly pressing issue because of the severity of the disorder, the controversies surrounding its diagnosis and treatment, and the possibility that widespread use of psychotropic medications in vulnerable children may precipitate the condition. The Workgroup recommends that the NIMH establish a collaborative multisite multidisciplinary Network of Research Programs on Pediatric-Onset Bipolar Disorder to achieve a better understanding of its causes, course, treatment, and prevention. The NIMH should develop a capacity-building plan to ensure the availability of trained investigators in the child and adolescent field. Mood disorders are among the most prevalent, recurrent, and disabling of all illnesses. They are often disorders of early onset. Although the NIMH has made important strides in mood disorders research, more data, beginning with at-risk infants, children, and adolescents, are needed concerning the etiology and developmental course of these disorders. A diverse program of multidisciplinary research is recommended to reduce the burden on children and families affected with these conditions.

Assessment of neuropsychological function through use of the Cambridge Neuropsychological Testing Automated Battery: performance in 4- to 12-year-old children.

In this article, children's performance on subtasks from the Cambridge Neuropsychological Testing Automated Battery (CANTAB) is described. Two samples were recruited, one of which included children who spoke English as a second language. Children in this group also completed subtests from the Wechsler Intelligence Scale for Children-Third Revision (WISC-III). Despite the fact that ESL children scored over 1 SD below the norm on the WISC-III Vocabulary subtest, there were no CANTAB performance distinctions between primary versus secondary English-language speakers. In addition, several aspects of CANTAB performance were significantly correlated with verbal and nonverbal IQ. When developmental trends were examined, findings indicated that several aspects of frontal lobe function (memory span, working memory, and planning skills) are not functionally mature, by the age of 12 years. Implications for use of the CANTAB in clinical studies are discussed.