Neonatal brain volume as a marker of differential susceptibility to parenting quality and its association with neurodevelopment across early childhood

Parenting quality is associated with child cognitive and executive functions (EF), which are important predictors of social and academic development. However, children vary in their susceptibility to parenting behaviors, and the neurobiological underpinnings of this susceptibility are poorly understood. In a prospective longitudinal study, we examined whether neonatal total brain volume (TBV) and subregions of interest (i.e., hippocampus (HC) and anterior cingulate gyrus (ACG)) moderate the association between maternal sensitivity and cognitive/EF development across early childhood. Neonates underwent a brain magnetic resonance imaging scan. Their cognitive performance and EF was characterized at 2.0 ± 0.1 years (N = 53) and at 4.9 ± 0.8 years (N = 36) of age. Maternal sensitivity was coded based on observation of a standardized play situation at 6-mo postpartum. Neonatal TBV moderated the association between maternal sensitivity and 2-year working memory as well as all 5-year cognitive outcomes, suggesting that the positive association between maternal sensitivity and child cognition was observed only among children with large or average but not small TBV as neonates. Similar patterns were observed for TBV-corrected HC and ACG volumes. The findings suggest that larger neonatal TBV, HC and ACG may underlie susceptibility to the environment and affect the degree to which parenting quality shapes long-term cognitive development

Neonatal hippocampal volume moderates the effects of early postnatal enrichment on cognitive development

Environmental enrichment, particularly during the early life phases of enhanced neuroplasticity, can stimulate cognitive development. However, individuals exhibit considerable variation in their response to environmental enrichment. Recent evidence suggests that certain neurophenotypes such as hippocampal size may index inter-individual differences in sensitivity to environmental conditions. We conducted a prospective, longitudinal investigation in a cohort of 75 mother-child dyads to investigate whether neonatal hippocampal volume moderates the effects of the postnatal environment on cognitive development. Newborn hippocampal volume was quantified shortly after birth (26.2 ± 12.5 days) by structural MRI. Measures of infant environmental enrichment (assessed by the IT-HOME) and cognitive state (assessed by the Bayley-III) were obtained at 6 months of age (6.09 ± 1.43 months). The interaction between neonatal hippocampal volume and enrichment predicted infant cognitive development (b = 0.01, 95 % CI [0.00, 0.02], t = 2.08, p =.04), suggesting that exposure to a stimulating environment had a larger beneficial effect on cognitive outcomes among infants with a larger hippocampus as neonates. Our findings suggest that the effects of the postnatal environment on infant cognitive development are conditioned, in part, upon characteristics of the newborn brain, and that newborn hippocampal volume is a candidate neurophenotype in this context

Maternal Interleukin-6 concentration during pregnancy is associated with variation in frontolimbic white matter and cognitive development in early life

Maternal inflammation during pregnancy can alter the trajectory of fetal brain development and increase risk for offspring psychiatric disorders. However, the majority of relevant research to date has been conducted in animal models. Here, in humans, we focus on the structural connectivity of frontolimbic circuitry as it is both critical for socioemotional and cognitive development, and commonly altered in a range of psychiatric disorders associated with intrauterine inflammation. Specifically, we test the hypothesis that elevated maternal concentration of the proinflammatory cytokine interleukin-6 (IL-6) during pregnancy will be associated with variation in microstructural properties of this circuitry in the neonatal period and across the first year of life. Pregnant mothers were recruited in early pregnancy and maternal blood samples were obtained for assessment of maternal IL-6 concentrations in early (12.6 ± 2.8 weeks [S.D.]), mid (20.4 ± 1.5 weeks [S.D.]) and late (30.3 ± 1.3 weeks [S.D.]) gestation. Offspring brain MRI scans were acquired shortly after birth (N = 86, scan age = 3.7 ± 1.7 weeks [S.D.]) and again at 12-mo age (N = 32, scan age = 54.0 ± 3.1 weeks [S.D.]). Diffusion Tensor Imaging (DTI) was used to characterize fractional anisotropy (FA) along the left and right uncinate fasciculus (UF), representing the main frontolimbic fiber tract. In N = 30 of the infants with serial MRI data at birth and 12-mo age, cognitive and socioemotional developmental status was characterized using the Bayley Scales of Infant Development. All analyses tested for potentially confounding influences of household income, prepregnancy Body-Mass-Index, obstetric risk, smoking during pregnancy, and infant sex, and outcomes at 12-mo age were additionally adjusted for the quality of the postnatal caregiving environment. Maternal IL-6 concentration (averaged across pregnancy) was prospectively and inversely associated with FA (suggestive of reduced integrity under high inflammatory conditions) in the newborn offspring (bi-lateral, p < 0.01) in the central portion of the UF proximal to the amygdala. Furthermore, maternal IL-6 concentration was positively associated with rate of FA increase across the first year of life (bi-lateral, p < 0.05), resulting in a null association between maternal IL-6 and UF FA at 12-mo age. Maternal IL-6 was also inversely associated with offspring cognition at 12-mo age, and this association was mediated by FA growth across the first year of postnatal life. Findings from the current study support the premise that susceptibility for cognitive impairment and potentially psychiatric disorders may be affected in utero, and that maternal inflammation may constitute an intrauterine condition of particular importance in this context

Intergenerational Effect of Maternal Exposure to Childhood Maltreatment on Newborn Brain Anatomy

Background Childhood maltreatment (CM) confers deleterious long-term consequences, and growing evidence suggests some of these effects may be transmitted across generations. We examined the intergenerational effect of maternal CM exposure on child brain structure and also addressed the hypothesis that this effect may start during the child's intrauterine period of life. Methods A prospective longitudinal study was conducted in a clinical convenience sample of 80 mother-child dyads. Maternal CM exposure was assessed using the Childhood Trauma Questionnaire. Structural magnetic resonance imaging was employed to characterize newborn global and regional brain (tissue) volumes near the time of birth. Results CM exposure was reported by 35% of the women. Maternal CM exposure was associated with lower child intracranial volume (F1,70 = 6.84, p =.011), which was primarily due to a global difference in cortical gray matter (F1,70 = 9.10, p =.004). The effect was independent of potential confounding variables, including maternal socioeconomic status, obstetric complications, obesity, recent interpersonal violence, pre- and early postpartum stress, gestational age at birth, infant sex, and postnatal age at magnetic resonance imaging scan. The observed group difference between offspring of CM-exposed mothers versus nonexposed mothers was 6%. Conclusions These findings represent the first report to date associating maternal CM exposure with variation in newborn brain structure. These observations support our hypothesis of intergenerational transmission of the effects of maternal CM exposure on child brain development and suggest this effect may originate during the child's intrauterine period of life, which may have downstream neurodevelopmental consequences

Determining global mean-first-passage time of random walks on Vicsek fractals using eigenvalues of Laplacian matrices

The family of Vicsek fractals is one of the most important and frequently-studied regular fractal classes, and it is of considerable interest to understand the dynamical processes on this treelike fractal family. In this paper, we investigate discrete random walks on the Vicsek fractals, with the aim to obtain the exact solutions to the global mean first-passage time (GMFPT), defined as the average of first-passage time (FPT) between two nodes over the whole family of fractals. Based on the known connections between FPTs, effective resistance, and the eigenvalues of graph Laplacian, we determine implicitly the GMFPT of the Vicsek fractals, which is corroborated by numerical results. The obtained closed-form solution shows that the GMFPT approximately grows as a power-law function with system size (number of all nodes), with the exponent lies between 1 and 2. We then provide both the upper bound and lower bound for GMFPT of general trees, and show that leading behavior of the upper bound is the square of system size and the dominating scaling of the lower bound varies linearly with system size. We also show that the upper bound can be achieved in linear chains and the lower bound can be reached in star graphs. This study provides a comprehensive understanding of random walks on the Vicsek fractals and general treelike networks.Comment: Definitive version accepted for publication in Physical Review

Agronomic performance of super-sweet corn genotypes in the north of Rio de Janeiro.

We investigated the agronomic performance of super-sweet corn genotypes. Super-sweet corn genotypes were backcrossed with regionally adapted field varieties (CIMMYT 8 and Piranão 8). Eight morphological and yield-related traits were evaluated. A significant effect of interaction was observed between the five groups of genotypes (donor parents; super-sweet backcrossed parents; super-sweet intervarietal hybrids; common intervarietal corn hybrids; and field corn populations). Despite the low yield of genotype SH 2 Piranão, the hybrids resulting from interbreeding of the backcrossed parents for the improvement of super-sweet corn were promising. The agronomic performance of the super-sweet parents and their hybrids indicates the possibility of breeding lines with high genetic value to obtain single-cross hybrids and cultivars of super-sweet corn adapted to the northern region of the State of Rio de Janeiro

White matter fiber-based analysis of T1w/T2w ratio map

Purpose: To develop, test, evaluate and apply a novel tool for the white matter fiber-based analysis of T1w/T2w ratio maps quantifying myelin content. Background: The cerebral white matter in the human brain develops from a mostly non-myelinated state to a nearly fully mature white matter myelination within the first few years of life. High resolution T1w/T2w ratio maps are believed to be effective in quantitatively estimating myelin content on a voxel-wise basis. We propose the use of a fiber-tract-based analysis of such T1w/T2w ratio data, as it allows us to separate fiber bundles that a common regional analysis imprecisely groups together, and to associate effects to specific tracts rather than large, broad regions. Methods: We developed an intuitive, open source tool to facilitate such fiber-based studies of T1w/T2w ratio maps. Via its Graphical User Interface (GUI) the tool is accessible to non-technical users. The framework uses calibrated T1w/T2w ratio maps and a prior fiber atlas as an input to generate profiles of T1w/T2w values. The resulting fiber profiles are used in a statistical analysis that performs along-tract functional statistical analysis. We applied this approach to a preliminary study of early brain development in neonates. Results: We developed an open-source tool for the fiber based analysis of T1w/T2w ratio maps and tested it in a study of brain development

Maternal Cortisol Concentrations During Pregnancy and Sex-Specific Associations With Neonatal Amygdala Connectivity and Emerging Internalizing Behaviors

Background: Maternal cortisol during pregnancy has the potential to influence rapidly developing fetal brain systems that are commonly altered in neurodevelopmental and psychiatric disorders. Research examining maternal cortisol concentrations across pregnancy and offspring neurodevelopment proximal to birth is needed to advance understanding in this area and lead to insight into the etiology of these disorders. Methods: Participants were 70 adult women recruited during early pregnancy and their infants born after 34 weeks gestation. Maternal cortisol concentrations were assessed serially over 4 days in early, mid, and late gestation. Resting state functional connectivity magnetic resonance imaging of the neonatal amygdala was examined. Mothers reported on children's internalizing behavior problems at 24 months of age. Results: Maternal cortisol concentrations during pregnancy were significantly associated with neonatal amygdala connectivity in a sex-specific manner. Elevated maternal cortisol was associated with stronger amygdala connectivity to brain regions involved in sensory processing and integration, as well as the default mode network in girls, and with weaker connectivity to these brain regions in boys. Elevated maternal cortisol was associated with higher internalizing symptoms in girls only, and this association was mediated by stronger neonatal amygdala connectivity. Conclusions: Normative variation in maternal cortisol during pregnancy is associated with the coordinated functioning of the amygdala soon after birth in a sex-specific manner. The identified pathway from maternal cortisol to higher internalizing symptoms in girls via alterations in neonatal amygdala connectivity may be relevant for the etiology of sex differences in internalizing psychiatric disorders, which are more prevalent in women

Maternal Systemic Interleukin-6 During Pregnancy Is Associated With Newborn Amygdala Phenotypes and Subsequent Behavior at 2 Years of Age

Background Maternal inflammation during pregnancy increases the risk for offspring psychiatric disorders and other adverse long-term health outcomes. The influence of inflammation on the developing fetal brain is hypothesized as one potential mechanism but has not been examined in humans. Methods Participants were adult women (N = 86) who were recruited during early pregnancy and whose offspring were born after 34 weeks’ gestation. A biological indicator of maternal inflammation (interleukin-6) that has been shown to influence fetal brain development in animal models was quantified serially in early, mid-, and late pregnancy. Structural and functional brain magnetic resonance imaging scans were acquired in neonates shortly after birth. Infants’ amygdalae were individually segmented for measures of volume and as seeds for resting state functional connectivity. At 24 months of age, children completed a snack delay task to assess impulse control. Results Higher average maternal interleukin-6 concentration during pregnancy was prospectively associated with larger right amygdala volume and stronger bilateral amygdala connectivity to brain regions involved in sensory processing and integration (fusiform, somatosensory cortex, and thalamus), salience detection (anterior insula), and learning and memory (caudate and parahippocampal gyrus). Larger newborn right amygdala volume and stronger left amygdala connectivity were in turn associated with lower impulse control at 24 months of age, and mediated the association between higher maternal interleukin-6 concentrations and lower impulse control. Conclusions These findings provide new evidence in humans linking maternal inflammation during pregnancy with newborn brain and emerging behavioral phenotypes relevant for psychiatric disorders. A better understanding of intrauterine conditions that influence offspring disease susceptibility is warranted to inform targeted early intervention and prevention efforts

DCC gene network in the prefrontal cortex is associated with total brain volume in childhood

BACKGROUND: Genetic variation in the guidance cue DCC gene is linked to psychopathologies involving dysfunction in the prefrontal cortex. We created an expression-based polygenic risk score (ePRS) based on the DCC coexpression gene network in the prefrontal cortex, hypothesizing that it would be associated with individual differences in total brain volume. METHODS: We filtered single nucleotide polymorphisms (SNPs) from genes coexpressed with DCC in the prefrontal cortex obtained from an adult postmortem donors database (BrainEAC) for genes enriched in children 1.5 to 11 years old (BrainSpan). The SNPs were weighted by their effect size in predicting gene expression in the prefrontal cortex, multiplied by their allele number based on an individual's genotype data, and then summarized into an ePRS. We evaluated associations between the DCC ePRS and total brain volume in children in 2 community-based cohorts: the Maternal Adversity, Vulnerability and Neurodevelopment (MAVAN) and University of California, Irvine (UCI) projects. For comparison, we calculated a conventional PRS based on a genome-wide association study of total brain volume. RESULTS: Higher ePRS was associated with higher total brain volume in children 8 to 10 years old (β = 0.212, p = 0.043; n = 88). The conventional PRS at several different thresholds did not predict total brain volume in this cohort. A replication analysis in an independent cohort of newborns from the UCI study showed an association between the ePRS and newborn total brain volume (β = 0.101, p = 0.048; n = 80). The genes included in the ePRS demonstrated high levels of coexpression throughout the lifespan and are primarily involved in regulating cellular function. LIMITATIONS: The relatively small sample size and age differences between the main and replication cohorts were limitations. CONCLUSION: Our findings suggest that the DCC coexpression network in the prefrontal cortex is critically involved in whole brain development during the first decade of life. Genes comprising the ePRS are involved in gene translation control and cell adhesion, and their expression in the prefrontal cortex at different stages of life provides a snapshot of their dynamic recruitment