Immunology of SARS-CoV-2 infection in children.

Children and adolescents exhibit a broad range of clinical outcomes from SARS-CoV-2 infection, with the majority having minimal to mild symptoms. Additionally, some succumb to a severe hyperinflammatory post-infectious complication called multisystem inflammatory syndrome in children (MIS-C), predominantly affecting previously healthy individuals. Studies characterizing the immunological differences associated with these clinical outcomes have identified pathways important for host immunity to SARS-CoV-2 and innate modulators of disease severity. In this Review, we delineate the immunological mechanisms underlying the spectrum of pediatric immune response to SARS-CoV-2 infection in comparison with that of adults.

Sialylated Milk Oligosaccharides Promote Microbiota-Dependent Growth in Models of Infant Undernutrition.

Identifying interventions that more effectively promote healthy growth of children with undernutrition is a pressing global health goal. Analysis of human milk oligosaccharides (HMOs) from 6-month-postpartum mothers in two Malawian birth cohorts revealed that sialylated HMOs are significantly less abundant in those with severely stunted infants. To explore this association, we colonized young germ-free mice with a consortium of bacterial strains cultured from the fecal microbiota of a 6-month-old stunted Malawian infant and fed recipient animals a prototypic Malawian diet with or without purified sialylated bovine milk oligosaccharides (S-BMO). S-BMO produced a microbiota-dependent augmentation of lean body mass gain, changed bone morphology, and altered liver, muscle, and brain metabolism in ways indicative of a greater ability to utilize nutrients for anabolism. These effects were also documented in gnotobiotic piglets using the same consortium and Malawian diet. These preclinical models indicate a causal, microbiota-dependent relationship between S-BMO and growth promotion.

Cultivating healthy growth and nutrition through the gut microbiota.

Microbiota assembly is perturbed in children with undernutrition, resulting in persistent microbiota immaturity that is not rescued by current nutritional interventions. Evidence is accumulating that this immaturity is causally related to the pathogenesis of undernutrition and its lingering sequelae. Preclinical models in which human gut communities are replicated in gnotobiotic mice have provided an opportunity to identify and predict the effects of different dietary ingredients on microbiota structure, expressed functions, and host biology. This capacity sets the stage for proof-of-concept tests designed to deliberately shape the developmental trajectory and configurations of microbiota in children representing different geographies, cultural traditions, and states of health. Developing these capabilities for microbial stewardship is timely given the global health burden of childhood undernutrition, the effects of changing eating practices brought about by globalization, and the realization that affordable nutritious foods need to be developed to enhance our capacity to cultivate healthier microbiota in populations at risk for poor nutrition.

MC3R links nutritional state to childhood growth and the timing of puberty.

The state of somatic energy stores in metazoans is communicated to the brain, which regulates key aspects of behaviour, growth, nutrient partitioning and development1. The central melanocortin system acts through melanocortin 4 receptor (MC4R) to control appetite, food intake and energy expenditure2. Here we present evidence that MC3R regulates the timing of sexual maturation, the rate of linear growth and the accrual of lean mass, which are all energy-sensitive processes. We found that humans who carry loss-of-function mutations in MC3R, including a rare homozygote individual, have a later onset of puberty. Consistent with previous findings in mice, they also had reduced linear growth, lean mass and circulating levels of IGF1. Mice lacking Mc3r had delayed sexual maturation and an insensitivity of reproductive cycle length to nutritional perturbation. The expression of Mc3r is enriched in hypothalamic neurons that control reproduction and growth, and expression increases during postnatal development in a manner that is consistent with a role in the regulation of sexual maturation. These findings suggest a bifurcating model of nutrient sensing by the central melanocortin pathway with signalling through MC4R controlling the acquisition and retention of calories, whereas signalling through MC3R primarily regulates the disposition of calories into growth, lean mass and the timing of sexual maturation.

Early-emerging combinatorial thought: Human infants flexibly combine kind and quantity concepts.

Combinatorial thought, or the ability to combine a finite set of concepts into a myriad of complex ideas and knowledge structures, is the key to the productivity of the human mind and underlies communication, science, technology, and art. Despite the importance of combinatorial thought for human cognition and culture, its developmental origins remain unknown. To address this, we tested whether 12-mo-old infants (N = 60), who cannot yet speak and only understand a handful of words, can combine quantity and kind concepts activated by verbal input. We proceeded in two steps: first, we taught infants two novel labels denoting quantity (e.g., "mize" for 1 item; "padu" for 2 items, Experiment 1). Then, we assessed whether they could combine quantity and kind concepts upon hearing complex expressions comprising their labels (e.g., "padu duck", Experiments 2-3). At test, infants viewed four different sets of objects (e.g., 1 duck, 2 ducks, 1 ball, 2 balls) while being presented with the target phrase (e.g., "padu duck") naming one of them (e.g., 2 ducks). They successfully retrieved and combined on-line the labeled concepts, as evidenced by increased looking to the named sets but not to distractor sets. Our results suggest that combinatorial processes for building complex representations are available by the end of the first year of life. The infant mind seems geared to integrate concepts in novel productive ways. This ability may be a precondition for deciphering the ambient language(s) and building abstract models of experience that enable fast and flexible learning.

Cortical representations of numbers and nonsymbolic quantities expand and segregate in children from 5 to 8 years of age.

Number symbols, such as Arabic numerals, are cultural inventions that have transformed human mathematical skills. Although their acquisition is at the core of early elementary education in children, it remains unknown how the neural representations of numerals emerge during that period. It is also unclear whether these relate to an ontogenetically earlier sense of approximate quantity. Here, we used multivariate fMRI adaptation coupled with within- and between-format machine learning to probe the cortical representations of Arabic numerals and approximate nonsymbolic quantity in 89 children either at the beginning (age 5) or four years into formal education (age 8). Although the cortical representations of both numerals and nonsymbolic quantities expanded from age 5 to age 8, these representations also segregated with learning and development. Specifically, a format-independent neural representation of quantity was found in the right parietal cortex, but only for 5-year-olds. These results are consistent with the so-called symbolic estrangement hypothesis, which argues that the relation between symbolic and nonsymbolic quantity weakens with exposure to formal mathematics in children.

Diverse mathematical knowledge among indigenous Amazonians.

We investigate number and arithmetic learning among a Bolivian indigenous people, the Tsimane', for whom formal schooling is comparatively recent in history and variable in both extent and consistency. We first present a large-scale meta-analysis on child number development involving over 800 Tsimane' children. The results emphasize the impact of formal schooling: Children are only found to be full counters when they have attended school, suggesting the importance of cultural support for early mathematics. We then test especially remote Tsimane' communities and document the development of specialized arithmetical knowledge in the absence of direct formal education. Specifically, we describe individuals who succeed on arithmetic problems involving the number five-which has a distinct role in the local economy-even though they do not succeed on some lower numbers. Some of these participants can perform multiplication with fives at greater accuracy than addition by one. These results highlight the importance of cultural factors in early mathematics and suggest that psychological theories of number where quantities are derived from lower numbers via repeated addition (e.g., a successor function) are unlikely to explain the diversity of human mathematical ability.

Development of neonatal connectome dynamics and its prediction for cognitive and language outcomes at age 2.

The functional brain connectome is highly dynamic over time. However, how brain connectome dynamics evolves during the third trimester of pregnancy and is associated with later cognitive growth remains unknown. Here, we use resting-state functional Magnetic Resonance Imaging (MRI) data from 39 newborns aged 32 to 42 postmenstrual weeks to investigate the maturation process of connectome dynamics and its role in predicting neurocognitive outcomes at 2 years of age. Neonatal brain dynamics is assessed using a multilayer network model. Network dynamics decreases globally but increases in both modularity and diversity with development. Regionally, module switching decreases with development primarily in the lateral precentral gyrus, medial temporal lobe, and subcortical areas, with a higher growth rate in primary regions than in association regions. Support vector regression reveals that neonatal connectome dynamics is predictive of individual cognitive and language abilities at 2  years of age. Our findings highlight network-level neural substrates underlying early cognitive development.

Spatiotemporal dynamics of cortical somatosensory network in typically developing children.

Sense of touch is essential for our interactions with external objects and fine control of hand actions. Despite extensive research on human somatosensory processing, it is still elusive how involved brain regions interact as a dynamic network in processing tactile information. Few studies probed temporal dynamics of somatosensory information flow and reported inconsistent results. Here, we examined cortical somatosensory processing through magnetic source imaging and cortico-cortical coupling dynamics. We recorded magnetoencephalography signals from typically developing children during unilateral pneumatic stimulation. Neural activities underlying somatosensory evoked fields were mapped with dynamic statistical parametric mapping, assessed with spatiotemporal activation analysis, and modeled by Granger causality. Unilateral pneumatic stimulation evoked prominent and consistent activations in the contralateral primary and secondary somatosensory areas but weaker and less consistent activations in the ipsilateral primary and secondary somatosensory areas. Activations in the contralateral primary motor cortex and supramarginal gyrus were also consistently observed. Spatiotemporal activation and Granger causality analysis revealed initial serial information flow from contralateral primary to supramarginal gyrus, contralateral primary motor cortex, and contralateral secondary and later dynamic and parallel information flows between the consistently activated contralateral cortical areas. Our study reveals the spatiotemporal dynamics of cortical somatosensory processing in the normal developing brain.

Children across societies enforce conventional norms but in culturally variable ways.

Individuals in all societies conform to their cultural group's conventional norms, from how to dress on certain occasions to how to play certain games. It is an open question, however, whether individuals in all societies actively enforce the group's conventional norms when others break them. We investigated third-party enforcement of conventional norms in 5- to 8-y-old children (n = 376) from eight diverse small-scale and large-scale societies. Children learned the rules for playing a new sorting game and then, observed a peer who was apparently breaking them. Across societies, observer children intervened frequently to correct their misguided peer (i.e., more frequently than when the peer was following the rules). However, both the magnitude and the style of interventions varied across societies. Detailed analyses of children's interactions revealed societal differences in children's verbal protest styles as well as in their use of actions, gestures, and nonverbal expressions to intervene. Observers' interventions predicted whether their peer adopted the observer's sorting rule. Enforcement of conventional norms appears to be an early emerging human universal that comes to be expressed in culturally variable ways.

Intersecting kinematic encoding and readout of intention in autism.

Observers with autism spectrum disorders (ASDs) find it difficult to read intentions from movements. However, the computational bases of these difficulties are unknown. Do these difficulties reflect an intention readout deficit, or are they more likely rooted in kinematic (dis-)similarities between typical and ASD kinematics? We combined motion tracking, psychophysics, and computational analyses to uncover single-trial intention readout computations in typically developing (TD) children (n = 35) and children with ASD (n = 35) who observed actions performed by TD children and children with ASD. Average intention discrimination performance was above chance for TD observers but not for ASD observers. However, single-trial analysis showed that both TD and ASD observers read single-trial variations in movement kinematics. TD readers were better able to identify intention-informative kinematic features during observation of TD actions; conversely, ASD readers were better able to identify intention-informative features during observation of ASD actions. Crucially, while TD observers were generally able to extract the intention information encoded in movement kinematics, those with autism were unable to do so. These results extend existing conceptions of mind reading in ASD by suggesting that intention reading difficulties reflect both an interaction failure, rooted in kinematic dissimilarity between TD and ASD kinematics (at the level of feature identification), and an individual readout deficit (at the level of information extraction), accompanied by an overall reduced sensitivity of intention readout to single-trial variations in movement kinematics.

Vaccination of household chickens results in a shift in young children's diet and improves child growth in rural Kenya.

Childhood growth faltering remains unacceptably high in sub-Saharan Africa. Rural communities dependent on household food production with limited off-farm income or liquid assets to bridge seasonal food availability are especially vulnerable. A cross-sectional survey in Siaya County, Kenya identified 23.5 and 4.8% of children under 5 y of age as stunted and wasted, respectively, using height-for-age Z (HAZ) scores to detect stunting and weight-for-height Z (WHZ) scores for wasting. Although these households are classified as living in poverty or extreme poverty with very limited off-farm income, households commonly have on-farm resources that could be developed to improve nutrition. While 95% of these households have chickens and consumption of eggs was shown to increase childhood growth by an average of 5%, the average flock size is small and constrained by high mortality due to infectious disease. We hypothesized that interventions to relieve this constraint would translate into household decisions influencing the diets and growth of children. Here, we show that vaccination of chickens against Newcastle disease has a causal impact on children's consumption of animal source foods rich in protein and micronutrients relative to a high-carbohydrate, grain-based diet. Children in treatment households (chicken vaccination) showed overall increases in scores for both HAZ and WHZ relative to control households, benefiting both girls and boys. The findings demonstrate the impact of directing interventions at common on-farm assets managed by women in rural communities and support programs to enhance productivity at the household level.

Comparing the reliability and predictive power of child, teacher, and guardian reports of noncognitive skills.

Children's noncognitive or socioemotional skills (e.g., persistence and self-control) are typically measured using surveys in which either children rate their own skills or adults rate the skills of children. For many purposes-including program evaluation and monitoring school systems-ratings are often collected from multiple perspectives about a single child (e.g., from both the child and an adult). Collecting data from multiple perspectives is costly, and there is limited evidence on the benefits of this approach. Using a longitudinal survey, this study compares children's noncognitive skills as reported by themselves, their guardians, and their teachers. Although reports from all three types of respondents are correlated with each other, teacher reports have the highest internal consistency and are the most predictive of children's later cognitive outcomes and behavior in school. The teacher reports add predictive power beyond baseline measures of Intelligence Quotient (IQ) for most outcomes in schools. Measures collected from children and guardians add minimal predictive power beyond the teacher reports.

Developmental Roots of Human Self-consciousness.

Human consciousness is considered in the perspective of early development. Infants and young children remind us that at its core, the problem of consciousness is primarily a problem of identity, in particular a problem of self-identity with others in mind. It is about how we feel and construe ourselves as an entity among other entities. It is about becoming co-conscious: Aware of oneself through the evaluative eyes of others. This development unfolds in the first 18 months of life, following major steps that are described, and arguably considered as a human trademark.

Perceptual Awareness in Human Infants: What is the Evidence?

Perceptual awareness in infants during the first year of life is understudied, despite the philosophical, scientific, and clinical importance of understanding how and when consciousness emerges during human brain development. Although parents are undoubtedly convinced that their infant is conscious, the lack of adequate experimental paradigms to address this question in preverbal infants has been a hindrance to research on this topic. However, recent behavioral and brain imaging studies have shown that infants are engaged in complex learning from an early age and that their brains are more structured than traditionally thought. I will present a rapid overview of these results, which might provide indirect evidence of early perceptual awareness and then describe how a more systematic approach to this question could stand within the framework of global workspace theory, which identifies specific signatures of conscious perception in adults. Relying on these brain signatures as a benchmark for conscious perception, we can deduce that it exists in the second half of the first year, whereas the evidence before the age of 5 months is less solid, mainly because of the paucity of studies. The question of conscious perception before term remains open, with the possibility of short periods of conscious perception, which would facilitate early learning. Advances in brain imaging and growing interest in this subject should enable us to gain a better understanding of this important issue in the years to come.

Social Perception in the Infant Brain and Its Link to Social Behavior.

The current longitudinal study (n = 98) utilized a developmental cognitive neuroscience approach to examine whether and how variability in social perception is linked to social behavior in early human development. Cortical responses to processing dynamic faces were investigated using functional near-infrared spectroscopy at 7 months. Individual differences in sociability were measured using the Early Childhood Behavior Questionnaire at 18 months. Confirming previous work with infants and adults, functional near-infrared spectroscopy results show that viewing changing faces recruited superior temporal cortices in 7-month-old infants, adding to the view that this brain system is specialized in social perception from early in ontogeny. Our longitudinal results show that greater engagement of the right superior temporal cortex at 7 months predicts higher levels of sociability at 18 months. This suggests that early variability in social perception is linked to later differences in overtly displayed social behavior, providing novel longitudinal evidence for a social brain-behavior association.

Neurodevelopmental subtypes of functional brain organization in the ABCD study using a rigorous analytic framework.

The current study demonstrates that an individual's resting-state functional connectivity (RSFC) is a dependable biomarker for identifying differential patterns of cognitive and emotional functioning during late childhood. Using baseline RSFC data from the Adolescent Brain Cognitive Development (ABCD) study, which includes children aged 9-11, we identified four distinct RSFC subtypes. We introduce an integrated methodological pipeline for testing the reliability and importance of these subtypes. In the Identification phase, Leiden Community Detection defined RSFC subtypes, with their reproducibility confirmed through a split-sample technique in the Validation stage. The Evaluation phase showed that distinct cognitive and mental health profiles are associated with each subtype, with the Predictive phase indicating that subtypes better predict various cognitive and mental health characteristics than individual RSFC connections. The Replication stage employed bootstrapping and down-sampling methods to substantiate the reproducibility of these subtypes further. This work allows future explorations of developmental trajectories of these RSFC subtypes.

Preschoolers' deception related to prefrontal cortex activation: An fNIRS study.

Deception is an essential part of children's moral development. Previous developmental studies have shown that children start to deceive at the age of 3 years, and as age increased to 5 years, almost all children were able to deceive for their own benefit. Although behavioral studies have indicated that the emergence and development of deception are related to cognitive abilities, their neural correlates remain poorly understood. Therefore, the present study examined the neural correlates underlying deception in preschool-aged children (N = 89, 44 % boys, age 3.13 to 5.96 years, Han Chinese) using functional near-infrared spectroscopy. A modified hide-and-seek paradigm was applied to elicit deceptive and truth-telling behaviors. The results showed that activation of bilateral dorsolateral prefrontal cortex was positively associated with the tendency to deceive an opponent in a competitive game in the 3-year-olds. In addition, 3-year-olds who showed a high tendency to deceive showed the same brain activation in the frontopolar area as 5-year-olds did when engaged in deception, whereas no such effect was found in 3-year-olds who never engaged in deception. These findings underscore the link between preschoolers' deception and prefrontal cortex function.

Evolving brain network dynamics in early childhood: Insights from modular graph metrics.

Modular dynamic graph theory metrics effectively capture the patterns of dynamic information interaction during human brain development. While existing research has employed modular algorithms to examine the overall impact of dynamic changes in community structure throughout development, there is a notable gap in understanding the cross-community dynamic changes within different functional networks during early childhood and their potential contributions to the efficiency of brain information transmission. This study seeks to address this gap by tracing the trajectories of cross-community structural changes within early childhood functional networks and modeling their contributions to information transmission efficiency. We analyzed 194 functional imaging scans from 83 children aged 2 to 8 years, who participated in passive viewing functional magnetic resonance imaging sessions. Utilizing sliding windows and modular algorithms, we evaluated three spatiotemporal metrics-temporal flexibility, spatiotemporal diversity, and within-community spatiotemporal diversity-and four centrality metrics: within-community degree centrality, eigenvector centrality, between-community degree centrality, and between-community eigenvector centrality. Mixed-effects linear models revealed significant age-related increases in the temporal flexibility of the default mode network (DMN), executive control network (ECN), and salience network (SN), indicating frequent adjustments in community structure within these networks during early childhood. Additionally, the spatiotemporal diversity of the SN also displayed significant age-related increases, highlighting its broad pattern of cross-community dynamic interactions. Conversely, within-community spatiotemporal diversity in the language network exhibited significant age-related decreases, reflecting the network's gradual functional specialization. Furthermore, our findings indicated significant age-related increases in between-community degree centrality across the DMN, ECN, SN, language network, and dorsal attention network, while between-community eigenvector centrality also increased significantly for the DMN, ECN, and SN. However, within-community eigenvector centrality remained stable across all functional networks during early childhood. These results suggest that while centrality of cross-community interactions in early childhood functional networks increases, centrality within communities remains stable. Finally, mediation analysis was conducted to explore the relationships between age, brain dynamic graph metrics, and both global and local efficiency based on community structure. The results indicated that the dynamic graph metrics of the SN primarily mediated the relationship between age and the decrease in global efficiency, while those of the DMN, language network, ECN, dorsal attention network, and SN primarily mediated the relationship between age and the increase in local efficiency. This pattern suggests a developmental trajectory in early childhood from global information integration to local information segregation, with the SN playing a pivotal role in this transformation. This study provides novel insights into the mechanisms by which early childhood brain functional development impacts information transmission efficiency through cross-community adjustments in functional networks.