Multilayer network associations between the exposome and childhood brain development.

Growing up in a high poverty neighborhood is associated with elevated risk for academic challenges and health problems. Here, we take a data-driven approach to exploring how measures of children's environments relate to the development of their brain structure and function in a community sample of children between the ages of 4 and 10 years. We constructed exposomes including measures of family socioeconomic status, children's exposure to adversity, and geocoded measures of neighborhood socioeconomic status, crime, and environmental toxins. We connected the exposome to two structural measures (cortical thickness and surface area, n = 170) and two functional measures (participation coefficient and clustering coefficient, n = 130). We found dense connections within exposome and brain layers and sparse connections between exposome and brain layers. Lower family income was associated with thinner visual cortex, consistent with the theory that accelerated development is detectable in early-developing regions. Greater neighborhood incidence of high blood lead levels was associated with greater segregation of the default mode network, consistent with evidence that toxins are deposited into the brain along the midline. Our study demonstrates the utility of multilayer network analysis to bridge environmental and neural explanatory levels to better understand the complexity of child development.

Developmental Correlates of Accelerated Molar Eruption in Early Childhood.

Background: Adversity has been linked to accelerated maturation. Molar eruption is a simple and scalable way to identify early maturation, but its developmental correlates remain unexplored. Thus, we examined whether accelerated maturation as indexed by molar eruption is associated with children's mental health or cognitive skills. Methods: Molar eruption was evaluated from T2-weighted magnetic resonance imaging in 117 children (63 female; ages 4-7 years). Parents reported on child mental health with the Child Behavior Checklist. Children completed standardized assessments of fluid reasoning, working memory, processing speed, crystallized knowledge, and math performance. Relationships between molar eruption and developmental outcomes were examined using linear models, with age, gender, and stress risk as covariates. Results: Earlier molar eruption was positively associated with children's externalizing symptoms (false discovery rate-corrected p [pFDR] = .027) but not internalizing symptoms, and the relationship with externalizing symptoms did not hold when controlling for stress risk. Earlier molar eruption was negatively associated with fluid reasoning (pFDR < .001), working memory (pFDR = .033), and crystallized knowledge (pFDR = .001). The association between molar eruption and both reasoning and crystallized knowledge held when controlling for stress risk. Molar eruption also partially mediated associations between stress risk and both reasoning (proportion mediated = 0.273, p = .004) and crystallized knowledge (proportion mediated = 0.126, p = .016). Conclusions: Accelerated maturation, as reflected in early molar eruption, may have consequences for cognitive development, perhaps because it constrains brain plasticity. Knowing the pace of a child's maturation may provide insight into the impact of a child's stress history on their cognitive development.

Prenatal environment is associated with the pace of cortical network development over the first three years of life.

Environmental influences on brain structure and function during early development have been well-characterized. In pre-registered analyses, we test the theory that socioeconomic status (SES) is associated with differences in trajectories of intrinsic brain network development from birth to three years (n = 261). Prenatal SES is associated with developmental increases in cortical network segregation, with neonates and toddlers from lower-SES backgrounds showing a steeper increase in cortical network segregation with age, consistent with accelerated network development. Associations between SES and cortical network segregation occur at the local scale and conform to a sensorimotor-association hierarchy of cortical organization. SES-associated differences in cortical network segregation are associated with language abilities at two years, such that lower segregation is associated with improved language abilities. These results yield key insight into the timing and directionality of associations between the early environment and trajectories of cortical development.

Individual differences in T1w/T2w ratio development during childhood.

Myelination is a key developmental process that promotes rapid and efficient information transfer. Myelin also stabilizes existing brain networks and thus may constrain neuroplasticity, defined here as the brain's potential to change in response to experiences rather than the canonical definition as the process of change. Characterizing individual differences in neuroplasticity may shed light on mechanisms by which early experiences shape learning, brain and body development, and response to interventions. The T1-weighted/T2-weighted (T1w/T2w) MRI signal ratio is a proxy measure of cortical microstructure and thus neuroplasticity. Here, in pre-registered analyses, we investigated individual differences in T1w/T2w ratios in children (ages 4-10, n = 157). T1w/T2w ratios were positively associated with age within early-developing sensorimotor and attention regions. We also tested whether socioeconomic status, cognition (crystallized knowledge or fluid reasoning), and biological age (as measured with molar eruption) were related to T1w/T2w signal but found no significant effects. Associations among T1w/T2w ratios, early experiences, and cognition may emerge later in adolescence and may not be strong enough to detect in moderate sample sizes.

The Age of Reason: Functional Brain Network Development during Childhood.

Human childhood is characterized by dramatic changes in the mind and brain. However, little is known about the large-scale intrinsic cortical network changes that occur during childhood because of methodological challenges in scanning young children. Here, we overcome this barrier by using sophisticated acquisition and analysis tools to investigate functional network development in children between the ages of 4 and 10 years ([Formula: see text]; 50 female, 42 male). At multiple spatial scales, age is positively associated with brain network segregation. At the system level, age was associated with segregation of systems involved in attention from those involved in abstract cognition, and with integration among attentional and perceptual systems. Associations between age and functional connectivity are most pronounced in visual and medial prefrontal cortex, the two ends of a gradient from perceptual, externally oriented cortex to abstract, internally oriented cortex. These findings suggest that both ends of the sensory-association gradient may develop early, in contrast to the classical theories that cortical maturation proceeds from back to front, with sensory areas developing first and association areas developing last. More mature patterns of brain network architecture, controlling for age, were associated with better visuospatial reasoning abilities. Our results suggest that as cortical architecture becomes more specialized, children become more able to reason about the world and their place in it.SIGNIFICANCE STATEMENT Anthropologists have called the transition from early to middle childhood the "age of reason", when children across cultures become more independent. We employ cutting-edge neuroimaging acquisition and analysis approaches to investigate associations between age and functional brain architecture in childhood. Age was positively associated with segregation between cortical systems that process the external world and those that process abstract phenomena like the past, future, and minds of others. Surprisingly, we observed pronounced development at both ends of the sensory-association gradient, challenging the theory that sensory areas develop first and association areas develop last. Our results open new directions for research into how brains reorganize to support rapid gains in cognitive and socioemotional skills as children reach the age of reason.

Early stressful experiences are associated with reduced neural responses to naturalistic emotional and social content in children.

How do children's experiences relate to their naturalistic emotional and social processing? Because children can struggle with tasks in the scanner, we collected fMRI data while 4-to-11-year-olds watched a short film with positive and negative emotional events, and rich parent-child interactions (n = 70). We captured broad, normative stressful experiences by examining socioeconomic status (SES) and stressful life events, as well as children's more proximal experiences with their parents. For a sub-sample (n = 30), parenting behaviors were measured during a parent-child interaction, consisting of a picture book, a challenging puzzle, and free play with novel toys. We characterized positive parenting behaviors (e.g., warmth, praise) and negative parenting behaviors (e.g., harsh tone, physical control). We found that higher SES was related to greater activity in medial orbitofrontal cortex during parent-child interaction movie events. Negative parenting behaviors were associated with less activation of the ventral tegmental area and cerebellum during positive emotional events. In a region-of-interest analysis, we found that stressful life events and negative parenting behaviors were associated with less activation of the amygdala during positive emotional events. These exploratory results demonstrate the promise of using movie fMRI to study how early experiences may shape emotional, social, and motivational processes.

Individual differences in frontoparietal plasticity in humans.

Neuroplasticity, defined as the brain's potential to change in response to its environment, has been extensively studied at the cellular and molecular levels. Work in animal models suggests that stimulation to the ventral tegmental area (VTA) enhances plasticity, and that myelination constrains plasticity. Little is known, however, about whether proxy measures of these properties in the human brain are associated with learning. Here, we investigated the plasticity of the frontoparietal system by asking whether VTA resting-state functional connectivity and myelin map values (T1w/T2w ratios) predicted learning after short-term training on the adaptive n-back (n = 46, ages 18-25). We found that stronger baseline connectivity between VTA and lateral prefrontal cortex predicted greater improvements in accuracy. Lower myelin map values predicted improvements in response times, but not accuracy. Our findings suggest that proxy markers of neural plasticity can predict learning in humans.

Functional brain network community structure in childhood: Unfinished territories and fuzzy boundaries.

Adult cortex is organized into distributed functional communities. Yet, little is known about community architecture of children's brains. Here, we uncovered the community structure of cortex in childhood using fMRI data from 670 children aged 9-11 years (48% female, replication sample n=544, 56% female) from the Adolescent Brain and Cognitive Development study. We first applied a data-driven community detection approach to cluster cortical regions into communities, then employed a generative model-based approach called the weighted stochastic block model to further probe community interactions. Children showed similar community structure to adults, as defined by Yeo and colleagues in 2011, in early-developing sensory and motor communities, but differences emerged in transmodal areas. Children have more cortical territory in the limbic community, which is involved in emotion processing, than adults. Regions in association cortex interact more flexibly across communities, creating uncertainty for the model-based assignment algorithm, and perhaps reflecting cortical boundaries that are not yet solidified. Uncertainty was highest for cingulo-opercular areas involved in flexible deployment of cognitive control. Activation and deactivation patterns during a working memory task showed that both the data-driven approach and a set of adult communities statistically capture functional organization in middle childhood. Collectively, our findings suggest that community boundaries are not solidified by middle childhood.

Evaluating the sensitivity of functional connectivity measures to motion artifact in resting-state fMRI data.

Functional connectivity (FC) networks are typically inferred from resting-state fMRI data using the Pearson correlation between BOLD time series from pairs of brain regions. However, alternative methods of estimating functional connectivity have not been systematically tested for their sensitivity or robustness to head motion artifact. Here, we evaluate the sensitivity of eight different functional connectivity measures to motion artifact using resting-state data from the Human Connectome Project. We report that FC estimated using full correlation has a relatively high residual distance-dependent relationship with motion compared to partial correlation, coherence, and information theory-based measures, even after implementing rigorous methods for motion artifact mitigation. This disadvantage of full correlation, however, may be offset by higher test-retest reliability, fingerprinting accuracy, and system identifiability. FC estimated by partial correlation offers the best of both worlds, with low sensitivity to motion artifact and intermediate system identifiability, with the caveat of low test-retest reliability and fingerprinting accuracy. We highlight spatial differences in the sub-networks affected by motion with different FC metrics. Further, we report that intra-network edges in the default mode and retrosplenial temporal sub-networks are highly correlated with motion in all FC methods. Our findings indicate that the method of estimating functional connectivity is an important consideration in resting-state fMRI studies and must be chosen carefully based on the parameters of the study.

Early life stress is associated with earlier emergence of permanent molars.

Exposure to adversity can accelerate biological aging. However, existing biomarkers of early aging are either costly and difficult to collect, like epigenetic signatures, or cannot be detected until late childhood, like pubertal onset. We evaluated the hypothesis that early adversity is associated with earlier molar eruption, an easily assessed measure that has been used to track the length of childhood across primates. In a preregistered analysis (n = 117, ages 4 to 7 y), we demonstrate that lower family income and exposure to adverse childhood experiences (ACEs) are significantly associated with earlier eruption of the first permanent molars, as rated in T2-weighted magnetic resonance images (MRI). We replicate relationships between income and molar eruption in a population-representative dataset (National Health and Nutrition Examination Survey; n = 1,973). These findings suggest that the impact of stress on the pace of biological development is evident in early childhood, and detectable in the timing of molar eruption.

QSIPrep: an integrative platform for preprocessing and reconstructing diffusion MRI data.

Diffusion-weighted magnetic resonance imaging (dMRI) is the primary method for noninvasively studying the organization of white matter in the human brain. Here we introduce QSIPrep, an integrative software platform for the processing of diffusion images that is compatible with nearly all dMRI sampling schemes. Drawing on a diverse set of software suites to capitalize on their complementary strengths, QSIPrep facilitates the implementation of best practices for processing of diffusion images.

Environmental influences on the pace of brain development.

Childhood socio-economic status (SES), a measure of the availability of material and social resources, is one of the strongest predictors of lifelong well-being. Here we review evidence that experiences associated with childhood SES affect not only the outcome but also the pace of brain development. We argue that higher childhood SES is associated with protracted structural brain development and a prolonged trajectory of functional network segregation, ultimately leading to more efficient cortical networks in adulthood. We hypothesize that greater exposure to chronic stress accelerates brain maturation, whereas greater access to novel positive experiences decelerates maturation. We discuss the impact of variation in the pace of brain development on plasticity and learning. We provide a generative theoretical framework to catalyse future basic science and translational research on environmental influences on brain development.

Early childhood stress is associated with blunted development of ventral tegmental area functional connectivity.

Early life stress increases risk for later psychopathology, due in part to changes in dopaminergic brain systems that support reward processing and motivation. Work in animals has shown that early life stress has a profound impact on the ventral tegmental area (VTA), which provides dopamine to regions including nucleus accumbens (NAcc), anterior hippocampus, and medial prefrontal cortex (mPFC), with cascading effects over the course of development. However, little is known about how early stress exposure shifts the developmental trajectory of mesocorticolimbic circuitry in humans. In the current study, 88 four- to nine-year-old children participated in resting-state fMRI. Parents completed questionnaires on their children's chronic stress exposure, including socioeconomic status (SES) and adverse childhood experiences (ACEs). We found an age x SES interaction on VTA connectivity, such that children from higher SES backgrounds showed a positive relationship between age and VTA-mPFC connectivity. Similarly, we found an age x ACEs exposure interaction on VTA connectivity, such that children with no ACEs exposure showed a positive relationship between age and VTA-mPFC connectivity. Our findings suggest that early stress exposure relates to the blunted maturation of VTA connectivity in young children, which may lead to disrupted reward processing later in childhood and beyond.

Associations between Neighborhood SES and Functional Brain Network Development.

Higher socioeconomic status (SES) in childhood is associated with stronger cognitive abilities, higher academic achievement, and lower incidence of mental illness later in development. While prior work has mapped the associations between neighborhood SES and brain structure, little is known about the relationship between SES and intrinsic neural dynamics. Here, we capitalize upon a large cross-sectional community-based sample (Philadelphia Neurodevelopmental Cohort, ages 8-22 years, n = 1012) to examine associations between age, SES, and functional brain network topology. We characterize this topology using a local measure of network segregation known as the clustering coefficient and find that it accounts for a greater degree of SES-associated variance than mesoscale segregation captured by modularity. High-SES youth displayed stronger positive associations between age and clustering than low-SES youth, and this effect was most pronounced for regions in the limbic, somatomotor, and ventral attention systems. The moderating effect of SES on positive associations between age and clustering was strongest for connections of intermediate length and was consistent with a stronger negative relationship between age and local connectivity in these regions in low-SES youth. Our findings suggest that, in late childhood and adolescence, neighborhood SES is associated with variation in the development of functional network structure in the human brain.

Nutritional status of foster children in the U.S.: Implications for cognitive and behavioral development.

OBJECTIVE: Children in foster care are at greater risk for poor health, physical, cognitive, behavioral, and developmental outcomes than are children in the general population. Considerable research links early nutrition to later cognitive and behavioral outcomes. The aim of this narrative review is to examine the prevalence of poor nutrition and its relation to subsequent health and development in foster children. METHOD: Relevant studies for inclusion were identified from numerous sources (e.g., PubMed, Google Scholar, and reference sections). Inclusion criteria were studies published between 1990 and 2016 of (i) the nutritional status of children in foster care or (ii) the nutritional status of children exposed to early adversity (e.g., low-income and internationally adopted children) or (iii) the developmental effects of poor nutrition and micronutrient deficiencies. RESULTS: Two key findings that have adverse implications for cognitive development emerged: (i) the prevalence of anemia and iron-deficiency anemia is higher among foster children than among the general population of children in the U.S., and (ii) the developmental demands of catch-up growth post-placement may lead to micronutrient deficiencies even after children have begun sufficient dietary intake of these nutrients. Moreover, there is a paucity of recent studies on the nutritional status of children in foster care, despite the multiple factors that may place them at risk for malnutrition. CONCLUSION: Attention to nutritional status among care providers and medical professionals may remove one of the possible negative influences on foster children's development and in turn significantly alter their trajectories and place them on a more positive path early in life. Recommendations for further research, policy, and practice are discussed.