Maternal diabetes and obesity are established risk factors for adverse offspring health. Emerging evidence suggests that these fetal programming effects vary by sex, yet it remains unclear whether these factors independently or interactively influence early brain development. This prospective study included 1,965 infants from six international cohorts. Infant MRI was used to derive subcortical volumes (thalamus, amygdala, hippocampus, pallidum, putamen, caudate). ComBat harmonization was applied. Multiple linear regression tested main and interaction effects of maternal obesity, maternal diabetes, and sex, controlling for covariates with false discovery rate (FDR) corrections. Of the sample, 46

The first decade of life is marked by rapid reorganization of functional brain networks, yet normative longitudinal trajectories of key properties characterizing brain functional connectivity remain poorly defined. Using 1,436 resting-state fMRI scans from 633 children followed from birth to 10 years, we derived the first normative growth trajectories of functional connectivity maturation, network topology, and large-scale functional gradients. Network development followed a hierarchical, nonlinear pattern from primary to transmodal systems. Children later diagnosed with neurodevelopmental disorders showed disrupted functional gradient trajectories. Early measures of functional connectivity predicted later socioemotional and cognitive outcomes at 8 and 10 years of age. A deep learning brain-age prediction model revealed disorder-specific deviations, distinguishing risk groups in early childhood. Together, these findings establish normative reference curves for functional brain development and demonstrate the prognostic value of early functional connectivity measures, offering novel imaging biomarkers for the early identification of neurodevelopmental risk.

Most EEG studies of MDD examined mean differences in frequency-band-specific power between MDD patients and control subjects; however, a few studies looked for differences in temporal trends in power. We focused on overnight time trends in relative power using polysomnography studies of 544 patients with MDD and 1662 age- and sex-matched controls. We sought to replicate our finding on MDD with an additional 653 patients with depressive disorder (DD) and 1959 age- and sex-matched controls. For each subject, we estimated trends as regression slopes separately for 180 features defined by six frequency bands, five sleep stages, and six brain regions. Relative theta power during stage 2 (N2) non-rapid eye movement (NREM) sleep in the frontal and central regions of the brain increased more rapidly through time in MDD patients than in controls. Similar upward trends of relative theta power were also statistically significant in DD patients. If validated in a longitudinal study, the time trend in relative theta power in the N2 stage of the NREM sleep could potentially serve as a surrogate biomarker for monitoring the responses of patients with depressive disorders to treatment.

The conventional understanding of the cerebellum as a sole movement control center has become obsolete, given its role in various higher-order functions, including cognition, emotion, and social processing. As these functions emerge during infancy, it is logical to assume that the cerebellum’s functional organization must evolve in tandem or preemptively to underpin these functions. However, the longitudinal development of the cerebellum’s functional architecture during the crucial early years of infant life remains largely unexplored, highlighting a significant research gap. In this study, leveraging a large cohort of both male and female full-term (n=155) and preterm (n=67) infants, we aimed to delineate the development of within-cerebellum and cerebello-cortical functional connections during the first two years of life. Our findings highlight comprehensive functional synchronization within the neonatal cerebellum with a striking cortical projection focus on primary sensorimotor and visual cortices. While the within-cerebellum synchronization demonstrated early emergence in neonates and developmental stability during the initial two years, the cerebello-cortical projection patterns evolved dramatically, marked by specialization, shifting, and higher-order cortex integration, providing exciting evidence of the cerebellum’s involvement in higher-order functions from infancy. Furthermore, preterm infants exhibited decreased cerebello-cortical connectivity compared to their full-term counterparts, suggesting potential developmental alterations. These findings collectively illustrate a dynamic growth pattern of cerebellar functional organization marked by both within-cerebellum stability and cerebellar-cortical projection plasticity with significant implications for long-term cognitive and socioemotional development. Significance Statement The cerebellum is crucial for motor and higher-order cognitive and socioemotional processes. However, the role of early cerebellar development and its cortical projections in supporting these emerging functions during the first years of life remains poorly understood. Our study, based on a large cohort of full-term and preterm infants, reveals the early and stable functional organization of the cerebellar networks from birth to two years, alongside dynamic cerebello-cortical connectivity growth, reflecting both stability and developmental plasticity. We observed a dramatic shift in cerebello-cortical projections from sensorimotor to higher-order association cortices, highlighting its role in emerging higher-order functions. Moreover, diminished growth of these connections indicates possible developmental delays in preterm infants, emphasizing the cerebellum’s importance in early brain and behavioral development.

OBJECTIVE:Prenatal phthalate exposure is associated with adverse neurodevelopmental outcomes, yet data on impacts of early life exposure remains limited. We investigated phthalate and replacement plasticizer exposures from 2 weeks to 7 years of age in relation to brain anatomical attributes, using serial structural magnetic resonance imaging (sMRI). MATERIAL AND METHODS:Children were enrolled after birth into the UNC Baby Connectome Project, a longitudinal neuroimaging study (North Carolina, USA; 2017-2020). Urine samples (n = 406) were collected at each visit and analyzed for 17 phthalate and replacement plasticizer metabolites. Among 157 children contributing 369 sMRIs, we calculated metabolite-specific average exposures across each individual's urine samples and used linear mixed models to estimate longitudinal associations of log transformed, specific gravity-adjusted average metabolite concentrations with gray and white matter volume, and cortical volume, thickness, and surface area. We examined sex-specific differences in these associations. RESULTS:Higher average metabolite concentration was associated with lower gray matter volume (MCPP: (-1.73 cm3, 95 % CI: -3.36, -0.10) and higher white matter volume (∑DEHP: 2.28 cm3, 95 % CI: 0.08, 4.48). Among boys (n = 72, 140 sMRIs), MEP (-2.97 cm3, 95 % CI: -5.85, -0.09) and MiBP (-2.40 cm3, 95 % CI: -4.64, -0.15) were also associated with lower gray matter volume. Among females (n = 85, 229 MRIs), higher ∑DINCH exposure was associated with higher white matter volume (2.27 cm3, 95 % CI: 0.29, 4.25). We observed significant sex interactions for ∑DEHP with gray matter (p-interaction = 0.03) and ∑DINCH with white matter volume (p-interaction = 0.001). CONCLUSION:Early life phthalate/plasticizer exposure may differentially impact various brain region volumes in early childhood, with potential downstream consequences on functional development.

Evidence for sex differences in cognition in childhood is established, but less is known about the underlying neural mechanisms for these differences. Recent findings suggest the existence of brain-behavior relationship heterogeneities during infancy; however, it remains unclear whether sex underlies these heterogeneities during this critical period when sex-related behavioral differences arise. A sample of 316 infants was included with resting-state functional magnetic resonance imaging scans at neonate (3 weeks), 1 year and 2 years of age. We used multiple linear regression to test interactions between sex and resting-state functional connectivity on behavioral scores of working memory, inhibitory self-control, intelligence, and anxiety collected at 4 years of age. We found 6 age-specific, intra-hemispheric connections showing significant and robust sex differences in functional connectivity-behavior relationships. All connections are either with the prefrontal cortex or in regions with direct anatomical pathways to the prefrontal cortex. These sex differences in functional connectivity only emerge when associated with behavior and not in functional connectivity independently. Taken together, we capture robust and conserved brain mechanisms that are distinct to sex and are defined by their relationship to behavioral outcomes. Our results establish brain-behavior mechanisms as an important feature in the search for sex differences during development.

Maternal diabetes (MD) and maternal obesity (MO) during pregnancy are risk factors for early life adiposity, but the underlying neurobiological mechanisms are undefined. We aim to study the relationships between prenatal exposure to MD and MO and newborn subcortical volumes, and moderating effects of sex.

INTRODUCTION:Existing evidence suggests that exposure to phthalates is higher among younger age groups. However, limited knowledge exists on how phthalate exposure, as well as exposure to replacement plasticizers, di(isononyl) cyclohexane-1,2-dicarboxylate (DINCH) and di-2-ethylhexyl terephthalate (DEHTP), change from infancy through early childhood. METHODS:Urine samples were collected across the first 5 years of life from typically developing infants and young children enrolled between 2017 and 2020 in the longitudinal UNC Baby Connectome Project. From 438 urine samples among 187 participants, we quantified concentrations of monobutyl phthalate (MnBP), mono-3-carboxypropyl phthalate (MCPP), monoisobutyl phthalate (MiBP), monoethyl phthalate (MEP), monobenzyl phthalate (MBzP), and metabolites of di(2-ethylhexyl) phthalate (DEHP), diisonoyl phthalate (DiNP), DINCH and DEHTP. Specific gravity (SG) adjusted metabolite and molar sum concentrations were compared across age groups. Intraclass correlation coefficients (ICCs) were calculated among 122 participants with multiple urine specimens (373 samples). RESULTS:Most phthalate metabolites showed high detection frequencies (>80% of samples). Replacement plasticizers DINCH (58-60%) and DEHTP (>97%) were also commonly found. DiNP metabolites were less frequently detected (<10%). For some metabolites, SG-adjusted concentrations were inversely associated with age, with the highest concentrations found in the first year of life. ICCs revealed low to moderate reliability in metabolite measurements (ρ = 0.10-0.48) suggesting a high degree of within-individual variation in exposure among this age group. The first 6 months (compared to remaining age groups) showed an increased ratio of carboxylated metabolites of DEHP and DEHTP, compared to other common metabolites, but no clear age trends for DINCH metabolite ratios were observed. CONCLUSION:Metabolites of phthalates and replacements plasticizers were widely detected in infancy and early childhood, with the highest concentrations observed in the first year of life for several metabolites. Higher proportions of carboxylated metabolites of DEHP and DEHTP in younger age groups indicate potential differences in metabolism during infancy.

BACKGROUND:Poor prenatal maternal sleep is a pervasive, yet modifiable, health concern affecting maternal and foetal wellbeing. Experimental rodent studies demonstrate that prenatal maternal sleep deprivation affects offspring brain development and leads to adverse outcomes, including increased anxiety-like behaviour. We examined the relation between prenatal maternal sleep quality and neonatal white matter development and subsequent infant negative emotionality. METHODS:Participants included 116 mother-infant (53% female) dyads. Prenatal sleep quality was prospectively assessed three times during gestation (16, 29, and 35 gestational weeks) using the Pittsburgh Sleep Quality Index. Neonatal white matter, as indexed by fractional anisotropy (FA), was assessed via diffusion weighted magnetic resonance imaging. Negative emotionality was measured via behavioural observation and maternal report when the infant was 6-months of age. FINDINGS:More prenatal sleep problems across pregnancy were associated with higher neonatal FA in the uncinate fasciculus (left: b = 0.20, p = .004; right: b = 0.15, p = .027). Higher neonatal uncinate FA was linked to infant negative emotionality, and uncinate FA partially mediated the association between prenatal maternal sleep and behavioural observation of infant negative emotionality. INTERPRETATION:Findings highlight prenatal sleep as an environmental signal that affects the developing neonatal brain and later infant negative emotionality. FUNDING:National Institutes of Health (R01MH109662, R01HL155744, P50HD103573, K12AR084226, F32 Training fellowships MH125572, HL165844, MH106440, and diversity supplement R01HL155744-01S1).

Schizophrenia is a neurodevelopmental disorder associated with deficits in cognitive development and childhood psychopathology. Previous studies have focused on older children and the few studies of early childhood have yielded inconsistent findings. We studied cognitive development and psychopathology in children at familial high risk (FHR) of schizophrenia and matched controls from 1 to 6 years and hypothesized that FHR children would show consistent deficits across cognitive and behavioral measures in early childhood. Study design Cognitive development in children at high familial risk for schizophrenia or schizoaffective disorder (n = 33) and matched healthy controls (n = 66) was assessed at 1 and 2 years with the Mullen Scales of Early Learning, and at 4 and 6 years with the Stanford Binet Intelligence Scales, BRIEF-P/BRIEF and CANTAB. Psychopathology was assessed at 4 and 6 years with the BASC-2. General linear models were used to examine differences on outcome scores, and chi-square analyses were used to explore differences in the proportion of “at risk” or “below average” score profiles. Study results FHR children scored significantly lower than controls on Mullen Composite at age 2, and demonstrated broad deficits in IQ, executive function and working memory and 4 and 6 years. FHR children were also rated as significantly worse on most items of the BASC-2 at ages 4 and 6. Conclusions Children at FHR for schizophrenia demonstrate abnormal cognitive development and psychopathology at younger ages than previously detected, suggesting that early detection and intervention needs to be targeted to very early childhood.

Turner syndrome, caused by complete or partial loss of an X-chromosome, is often accompanied by specific cognitive challenges. Magnetic resonance imaging studies of adults and children with Turner syndrome suggest these deficits reflect differences in anatomical and functional connectivity. However, no imaging studies have explored connectivity in infants with Turner syndrome. Consequently, it is unclear when in development connectivity differences emerge. To address this gap, we compared functional connectivity and white matter microstructure of 1-year-old infants with Turner syndrome to typically developing 1-year-old boys and girls. We examined functional connectivity between the right precentral gyrus and five regions that show reduced volume in 1-year old infants with Turner syndrome compared to controls and found no differences. However, exploratory analyses suggested infants with Turner syndrome have altered connectivity between right supramarginal gyrus and left insula and right putamen. To assess anatomical connectivity, we examined diffusivity indices along the superior longitudinal fasciculus and found no differences. However, an exploratory analysis of 46 additional white matter tracts revealed significant group differences in nine tracts. Results suggest that the first year of life is a window in which interventions might prevent connectivity differences observed at later ages, and by extension, some of the cognitive challenges associated with Turner syndrome.

Genetic factors have been proven to be one of the major determinants in shaping the neonatal cerebral cortex. Previous research has demonstrated distinct genetic influences on the spatial patterns of cortical thickness (CT) and surface area (SA) in neonates, leading to their unique genetically informed parcellation maps. However, these parcellation maps were derived at coarse scales and only reliant on single cortical properties, making them unable to comprehensively characterize the fine-grained genetically regulated patterns of the neonatal cerebral cortex. To fill this knowledge gap, by combining genetic correlations of multiple cortical properties (CT and SA) based on 202 twin neonates' brain magnetic resonance (MR) images, we performed multi-view spectral clustering and revealed the first joint, fine-grained, genetically informed parcellation map of the neonatal cerebral cortex. The discovered parcellation maps comprehensively reflect genetically regulated detailed patterns of the neonatal brain.

Emotional regulation involves managing attention, affect, and behavior, and is essential for long-term health and well-being, including positive school adjustment. The purpose of this secondary data analysis from the Durham Child Health and Development Study was to explore how parent and teacher reported emotional regulation behaviors related to school adjustment outcomes (social skills, academic performance, and academic achievement) during early childhood. Parent and teacher reports on emotional regulation behaviors showed mixed concordance, however they correlated with critical aspects of school adjustment. Clinical and practical implications are discussed, including the role of psychiatric nurses in promoting positive emotional regulation and school adjustment outcomes across settings.

Stress activates the hypothalamic-pituitary-adrenal (HPA) axis, leading to high cortisol production, which is associated with damage to certain brain regions. We investigate the role of basal cortisol in shaping brain development in infancy through 2 questions: Q1) Are basal cortisol levels in early infancy associated with brain development during the first year of life? Q2) Do neonatal hippocampal and amygdala volumes predict cortisol levels later in infancy?

Amygdala function is implicated in the pathogenesis of autism spectrum disorder (ASD) and anxiety. We investigated associations between early trajectories of amygdala growth and anxiety and ASD outcomes at school age in two longitudinal studies: high- and low-familial likelihood for ASD, Infant Brain Imaging Study (IBIS, n=257) and typically developing (TD) community sample, Early Brain Development Study (EBDS, n=158). Infants underwent MRI scanning at up to 3 timepoints from neonate to 24 months. Anxiety was assessed at 6-12 years. Linear multilevel modeling tested whether amygdala volume growth was associated with anxiety symptoms at school age. In the IBIS sample, children with higher anxiety showed accelerated amygdala growth from 6 to 24 months. ASD diagnosis and ASD familial likelihood were not significant predictors. In the EBDS sample, amygdala growth from birth to 24 months was associated with anxiety. More anxious children had smaller amygdala volume and slower rates of amygdala growth. We explore reasons for the contrasting results between high-familial likelihood for ASD and TD samples, grounding results in the broader literature of variable associations between early amygdala volume and later anxiety. Results have the potential to identify mechanisms linking early amygdala growth to later anxiety in certain groups.