The pollutant perfluorohexane sulfonate (PFHxS) reduces serum thyroxine but does not alter thyroid action in the postnatal rat brain.

Known as "forever chemicals", per- and polyfluoroalkyl substances (PFAS) are synthetic compounds used in consumer goods but pose significant public health concerns, including disruption of the thyroid system. As thyroid hormones (THs) are required for normal brain development, PFAS may also be developmental neurotoxicants. However, this is not well understood. Here we examine the endocrine and neurodevelopmental consequences of perfluorohexane sulfonate (PFHxS) exposure in pregnant, lactating, and developing rats, and compare its effects to an anti-thyroid pharmaceutical (propylthiouracil, PTU) that induces thyroid-mediated developmental neurotoxicity. We show that PFHxS dramatically reduces maternal serum thyroxine (T4), nearly equivalently to PTU (-55 and -51%, respectively). However, only PTU increases thyroid stimulating hormone. The lactational transfer of PFHxS is significant and reduces pup serum T4 across the postnatal period. Surprisingly, brain THs are only minimally decreased by PFHxS, whereas PTU drastically diminishes them. Evaluation of brain TH action by phenotyping, RNA-Sequencing, and quantification of radial glia cell morphology supports that PTU interrupts TH signaling while PFHxS has limited to no effect. These data show that PFHxS induces abnormal serum TH profiles; however, there were no indications of hypothyroidism in the postnatal brain. We suggest the stark differences between the neurodevelopmental effects of PFHxS and a typical antithyroid agent may be due to its interaction with TH distributing proteins like transthyretin.

Arginine vasopressin activates serotonergic neurons in the dorsal raphe nucleus during neonatal development in vitro and in vivo.

Birth stress is a risk factor for psychiatric disorders and associated with exaggerated release of the stress hormone arginine vasopressin (AVP) into circulation and in the brain. In perinatal hippocampus, AVP activates GABAergic interneurons which leads to suppression of spontaneous network events and suggests a protective function of AVP on cortical networks during birth. However, the role of AVP in developing subcortical networks is not known. Here we tested the effect of AVP on the dorsal raphe nucleus (DRN) 5-hydroxytryptamine (5-HT, serotonin) system in male and female neonatal rats, since early 5-HT homeostasis is critical for the development of cortical brain regions and emotional behaviors. We show that AVP is strongly excitatory in neonatal DRN: it increases excitatory synaptic inputs of 5-HT neurons via V1A receptors in vitro and promotes their action potential firing through a combination of its effect on glutamatergic synaptic transmission and a direct effect on the excitability of these neurons. Furthermore, we identified two major firing patterns of neonatal 5-HT neurons in vivo, tonic regular firing and low frequency oscillations of regular spike trains and confirmed that these neurons are also activated by AVP in vivo. Finally, we show that the sparse vasopressinergic innervation in neonatal DRN originates exclusively from cell groups in medial amygdala and bed nucleus of stria terminalis. Hyperactivation of the neonatal 5-HT system by AVP during birth stress may impact its own functional development and affect the maturation of cortical target regions, which may increase the risk for psychiatric conditions later on.

Anesthetic neurotoxicity in the developing brain: an update on theinsights and implications for fetal surgery.

This review describes an in-depth analysis of the neurotoxicity associated with the anesthetic agents used during fetal surgery, intending to highlight the importance of understanding the effects of general anesthetics on the developing brain, particularly in the context of open fetal surgery, where high doses are applied to facilitate surgical access and augment uterine relaxation. We examined evidence from preclinical studies in rodents and primates, along with studies in human subjects, with the results collectively suggesting that general anesthetics can disrupt brain development and lead to long-lasting neurological deficits. Our review underscores the clinical implications of these findings, indicating an association between extensive anesthetic exposure in early life and subsequent cognitive deficits. The current standard of anesthetic care for fetal surgical procedures was scrutinized, and recommendations have been proposed to mitigate the risk of anesthetic neurotoxicity. These recommendations emphasize the need for careful selection of anesthetic techniques to minimize fetal exposure to potentially harmful agents. In conclusion, while the benefits of fetal surgery in addressing immediate risks often outweigh the potential neurotoxic effects of anesthesia, the long-term developmental impacts nevertheless warrant consideration. Our analysis suggests that the use of general anesthetics in fetal surgery, especially at high doses, poses a significant risk of developmental neurotoxicity. As such, it is imperative to explore safer alternatives, such as employing different methods of uterine relaxation and minimizing the use of general anesthetics, to achieve the necessary surgical conditions. Further research, particularly in clinical settings, is essential to fully understand the risks and benefits of anesthetic techniques in fetal surgery.

Unraveling the Molecular Mechanisms of the Neurodevelopmental Consequences of Fetal Protein Deficiency: Insights From Rodent Models and Public Health Implications.

Fetal brain development requires increased maternal protein intake to ensure that offspring reach their optimal cognitive potential in infancy and adulthood. While protein deficiency remains a prevalent issue in developing countries, it is also reemerging in Western societies due to the growing adoption of plant-based diets, some of which are monotonous and may fail to provide sufficient amino acids crucial for the brain's critical developmental phase. Confounding variables in human nutritional research have impeded our understanding of the precise impact of protein deficiency on fetal neurodevelopment, as well as its implications for childhood neurocognitive performance. Moreover, it remains unclear whether such deficiency could predispose to mental health problems in adulthood, mirroring observations in individuals exposed to prenatal famine. In this review, we sought to evaluate mechanistic data derived from rodent models, placing special emphasis on the involvement of neuroendocrine axes, the influence of sex and timing, epigenetic modifications, and cellular metabolism. Despite notable progress, critical knowledge gaps remain, including understanding the long-term reversibility of effects due to fetal protein restriction and the interplay between genetic predisposition and environmental factors. Enhancing our understanding of the precise mechanisms that connect prenatal nutrition to brain development in future research endeavors can be significantly advanced by integrating multiomics approaches and utilizing additional alternative models such as nonhuman primates. Furthermore, it is crucial to investigate potential interventions aimed at alleviating adverse outcomes. Ultimately, this research has profound implications for guiding public health strategies aimed at raising awareness about the crucial role of optimal maternal nutrition in supporting fetal neurodevelopment.

The Developmental Origins of Health and Disease theory posits that suboptimal conditions during early life exert a profound influence on adult health, potentially predisposing individuals to conditions such as neuropsychiatric disorders. By reviewing studies in rodents, we identified common mechanisms of how inadequate fetal protein uptake alters brain development and may contribute to anxiety, impaired memory function, and altered metabolism in adulthood. Adequate protein consumption during pregnancy is therefore critical to support healthy brain development.

High-resolution diffusion magnetic resonance imaging and spatial-transcriptomic in developing mouse brain.

Brain development is a highly complex process regulated by numerous genes at the molecular and cellular levels. Brain tissue exhibits serial microstructural changes during the development process. High-resolution diffusion magnetic resonance imaging (dMRI) affords a unique opportunity to probe these changes in the developing brain non-destructively. In this study, we acquired multi-shell dMRI datasets at 32 µm isotropic resolution to investigate the tissue microstructure alterations, which we believe to be the highest spatial resolution dMRI datasets obtained for postnatal mouse brains. We adapted the Allen Developing Mouse Brain Atlas (ADMBA) to integrate quantitative MRI metrics and spatial transcriptomics. Diffusion tensor imaging (DTI), diffusion kurtosis imaging (DKI), and neurite orientation dispersion and density imaging (NODDI) metrics were used to quantify brain development at different postnatal days. We demonstrated that the differential evolutions of fiber orientation distributions contribute to the distinct development patterns in white matter (WM) and gray matter (GM). Furthermore, the genes enriched in the nervous system that regulate brain structure and function were expressed in spatial correlation with age-matched dMRI. This study is the first one providing high-resolution dMRI, including DTI, DKI, and NODDI models, to trace mouse brain microstructural changes in WM and GM during postnatal development. This study also highlighted the genotype-phenotype correlation of spatial transcriptomics and dMRI, which may improve our understanding of brain microstructure changes at the molecular level.

Engineering human midbrain organoid microphysiological systems to model prenatal PFOS exposure.

Perfluorooctane sulfonate (PFOS), a class of synthetic chemicals detected in various environmental compartments, has been associated with dysfunctions of the human central nervous system (CNS). However, the underlying neurotoxicology of PFOS exposure is largely understudied due to the lack of relevant human models. Here, we report bioengineered human midbrain organoid microphysiological systems (hMO-MPSs) to recapitulate the response of a fetal human brain to multiple concurrent PFOS exposure conditions. Each hMO-MPS consists of an hMO on a fully 3D printed holder device with a perfusable organoid adhesion layer for enhancing air-liquid interface culturing. Leveraging the unique, simply-fabricated holder devices, hMO-MPSs are scalable, easy to use, and compatible with conventional well-plates, and allow easy transfer onto a multiple-electrode array (MEA) system for plug-and-play measurement of neural activity. Interestingly, the neural activity of hMO-MPSs initially increased and subsequently decreased by exposure to a concentration range of 0, 30, 100, to 300 µM of PFOS. Furthermore, PFOS exposure impaired neural development and promoted neuroinflammation in the engineered hMO-MPSs. Along with PFOS, our platform is broadly applicable for studies toxicology of various other environmental pollutants.

From preparation to post-processing: Insights into evoked and induced cortical activity during pre-cued motor reactions in children and adolescents.

INTRODUCTION: The motor system undergoes significant development throughout childhood and adolescence. The contingent negative variation (CNV), a brain response reflecting preparation for upcoming actions, offers valuable insights into these changes. However, previous CNV studies of motor preparation have primarily focused on adults, leaving a gap in our understanding of how cortical activity related to motor planning and execution matures in children and adolescents. METHODS: The study addresses this gap by investigating the maturation of motor preparation, pre-activation, and post-processing in 46 healthy, right-handed children and adolescents aged 5-16 years. To overcome the resolution limitations of previous studies, we combined 64-electrode high-density Electroencephalography (EEG) and advanced analysis techniques, such as event-related potentials (ERPs), mu-rhythm desynchronization as well as source localization approaches. The combined analyses provided an in-depth understanding of cortical activity during motor control. RESULTS: Our data showed that children exhibited prolonged reaction times, increased errors, and a distinct pattern of cortical activation compared to adolescents. The findings suggest that the supplementary motor area (SMA) plays a progressively stronger role in motor planning and response evaluation as children age. Additionally, we observe a decrease in sensory processing and post-movement activity with development, potentially reflecting increased efficiency. Interestingly, adolescent subjects, unlike young adults in previous studies, did not yet show contralateral activation of motor areas during the motor preparation phase (late CNV). CONCLUSION: The progressive increase in SMA activation and distinct cortical activation patterns in younger participants suggest immature motor areas. These immature regions might be a primary cause underlying the age-related increase in motor action control efficiency. Additionally, the study demonstrates a prolonged maturation of cortical motor areas, extending well into early adulthood, challenging the assumption that motor control is fully developed by late adolescence. This research, extending fundamental knowledge of motor control development, offers valuable insights that lay the foundation for understanding and treating motor control difficulties.

ABC Efflux Transporters and Solute Carriers in the Early Developing Brain of a Marsupial Monodelphis domestica (South American Gray Short-Tailed Opossum).

This study used a marsupial Monodelphis domestica, which is born very immature and most of its development is postnatal without placental protection. RNA-sequencing (RNA-Seq) was used to identify the expression of influx and efflux transporters (ATP-binding cassettes [ABCs] and solute carriers [SLCs]) and metabolizing enzymes in brains of newborn to juvenile Monodelphis. Results were compared to published data in the developing eutherian rat. To test the functionality of these transporters at similar ages, the entry of paracetamol (acetaminophen) into the brain and cerebrospinal fluid (CSF) was measured using liquid scintillation counting following a single administration of the drug along with its radiolabelled tracer [3H]. Drug permeability studies found that in Monodelphis, brain entry of paracetamol was already restricted at P5; it decreased further in the first week of life and then remained stable until the oldest age group tested (P110). Transcriptomic analysis of Monodelphis brain showed that expression of transporters and their metabolizing enzymes in early postnatal (P) pups (P0, P5, and P8) was relatively similar, but by P109, many more transcripts were identified. When transcriptomes of newborn Monodelphis brain and E19 rat brain and placenta were compared, several transporters present in the rat placenta were also found in the newborn Monodelphis brain. These were absent from E19 rat brain but were present in the adult rat brain. These data indicate that despite its extreme immaturity, the newborn Monodelphis brain may compensate for the lack of placental protection during early brain development by upregulating protective mechanisms, which in eutherian animals are instead present in the placenta.

Quantitative assessment of preoperative brain development in pediatric congenital heart disease patients by synthetic MRI.

OBJECTIVES: This study investigated the quantitative assessment and application of Synthetic MRI (SyMRI) for preoperative brain development in children with congenital heart disease (CHD). METHODS: Forty-three CHD patients aged 2-24 months were prospectively included in the observation group, and 43 healthy infants were included in the control group. The SyMRI scans were processed by postprocessing software to obtain T1, T2, and PD maps. The values of T1, T2, and PD in different brain regions were compared with the scores of the five ability areas of the Gesell Development Scale by Pearson correlation analysis. RESULTS: In the observation group, the T1 values of the posterior limb of the internal capsule (PLIC), Optic radiation (PTR), cerebral peduncle, centrum semiovale, occipital white matter, temporal white matter, and dentate nucleus were greater than those in the control group. In the observation group, the T2 values of the PLIC, PTR, frontal white matter, occipital white matter, temporal white matter, and dentate nucleus were greater than those in the control group. Pearson correlation analysis revealed that the observation group had significantly lower Development Scale scores. In the observation group, the T2 value of the splenium of the corpus callosum was significantly positively correlated with the personal social behavior score. The AUCs for diagnosing preoperative brain developmental abnormalities in children with CHD using T1 values of the temporal white matter and dentate nucleus were both greater than 0.60. CONCLUSIONS: Quantitative assessment using SyMRI can aid in the early detection of preoperative brain development abnormalities in children with CHD. CRITICAL RELEVANCE STATEMENT: T1 and T2 relaxation values from SyMRI can be considered as a quantitative imaging marker to detect abnormalities, allowing for early clinical evaluation and timely intervention, thereby reducing neurodevelopmental disorders in these children. KEY POINTS: T1 and T2 relaxation values by SyMRI are related to myelin development. Evaluated development quotient markers were lower in the observation compared to the control group. SyMRI can act as a reference indicator for brain development in CHD children.

Recapitulation and investigation of human brain development with neural organoids.

Organoids are 3D cultured tissues derived from stem cells that resemble the structure of living organs. Based on the accumulated knowledge of neural development, neural organoids that recapitulate neural tissue have been created by inducing self-organized neural differentiation of stem cells. Neural organoid techniques have been applied to human pluripotent stem cells to differentiate 3D human neural tissues in culture. Various methods have been developed to generate neural tissues of different regions. Currently, neural organoid technology has several significant limitations, which are being overcome in an attempt to create neural organoids that more faithfully recapitulate the living brain. The rapidly advancing neural organoid technology enables the use of living human neural tissue as research material and contributes to our understanding of the development, structure and function of the human nervous system, and is expected to be used to overcome neurological diseases and for regenerative medicine.

Unraveling the complexity of human brain: Structure, function in healthy and disease states.

The human brain stands as an intricate organ, embodying a nexus of structure, function, development, and diversity. This review delves into the multifaceted landscape of the brain, spanning its anatomical intricacies, diverse functional capacities, dynamic developmental trajectories, and inherent variability across individuals. The dynamic process of brain development, from early embryonic stages to adulthood, highlights the nuanced changes that occur throughout the lifespan. The brain, a remarkably complex organ, is composed of various anatomical regions, each contributing uniquely to its overall functionality. Through an exploration of neuroanatomy, neurophysiology, and electrophysiology, this review elucidates how different brain structures interact to support a wide array of cognitive processes, sensory perception, motor control, and emotional regulation. Moreover, it addresses the impact of age, sex, and ethnic background on brain structure and function, and gender differences profoundly influence the onset, progression, and manifestation of brain disorders shaped by genetic, hormonal, environmental, and social factors. Delving into the complexities of the human brain, it investigates how variations in anatomical configuration correspond to diverse functional capacities across individuals. Furthermore, it examines the impact of neurodegenerative diseases on the structural and functional integrity of the brain. Specifically, our article explores the pathological processes underlying neurodegenerative diseases, such as Alzheimer's, Parkinson's, and Huntington's diseases, shedding light on the structural alterations and functional impairments that accompany these conditions. We will also explore the current research trends in neurodegenerative diseases and identify the existing gaps in the literature. Overall, this article deepens our understanding of the fundamental principles governing brain structure and function and paves the way for a deeper understanding of individual differences and tailored approaches in neuroscience and clinical practice-additionally, a comprehensive understanding of structural and functional changes that manifest in neurodegenerative diseases.

Consistently lower volumes across thalamus nuclei in very premature-born adults.

Lasting thalamus volume reduction after preterm birth is a prominent finding. However, whether thalamic nuclei volumes are affected differentially by preterm birth and whether nuclei aberrations are relevant for cognitive functioning remains unknown. Using T1-weighted MR-images of 83 adults born very preterm (≤ 32 weeks' gestation; VP) and/or with very low body weight (≤ 1,500 g; VLBW) as well as of 92 full-term born (≥ 37 weeks' gestation) controls, we compared thalamic nuclei volumes of six subregions (anterior, lateral, ventral, intralaminar, medial, and pulvinar) across groups at the age of 26 years. To characterize the functional relevance of volume aberrations, cognitive performance was assessed by full-scale intelligence quotient using the Wechsler Adult Intelligence Scale and linked to volume reductions using multiple linear regression analyses. Thalamic volumes were significantly lower across all examined nuclei in VP/VLBW adults compared to controls, suggesting an overall rather than focal impairment. Lower nuclei volumes were linked to higher intensity of neonatal treatment, indicating vulnerability to stress exposure after birth. Furthermore, we found that single results for lateral, medial, and pulvinar nuclei volumes were associated with full-scale intelligence quotient in preterm adults, albeit not surviving correction for multiple hypotheses testing. These findings provide evidence that lower thalamic volume in preterm adults is observable across all subregions rather than focused on single nuclei. Data suggest the same mechanisms of aberrant thalamus development across all nuclei after premature birth.

Early nutritional influences on brain regions related to processing speed in children born preterm: A secondary analysis of a randomized trial.

BACKGROUND: Processing speed is a foundational skill supporting intelligence and executive function, areas often delayed in preterm-born children. The impact of early-life nutrition on gray matter facilitating processing speed for this vulnerable population is unknown. METHODS: Magnetic resonance imaging and the Wechsler Preschool and Primary Scale of Intelligence-IV Processing Speed Index were acquired in forty 5-year-old children born preterm with very low birth weight. Macronutrient (grams per kilogram per day) and mother's milk (percentage of feeds) intakes were prospectively collected in the first postnatal month and associations between early-life nutrition and the primary outcome of brain regions supporting processing speed were investigated. RESULTS: Children had a mean (SD) gestational age of 27.8 (1.8) weeks and 45% were male. Macronutrient intakes were unrelated, but mother's milk was positively related, to greater volumes in brain regions, including total cortical gray matter, cingulate gyri, and occipital gyri. CONCLUSION: First postnatal month macronutrient intakes showed no association, but mother's milk was positively associated, with volumetric measures of total and regional cortical gray matter related to processing speed in preterm-born children. This exploratory analysis suggests early-life mother's milk supports processing speed by impacting structural underpinnings. Further research is needed on this potential strategy to improve preterm outcomes.

Early rhombic lip Protogenin+ve stem cells in a human-specific neurovascular niche initiate and maintain group 3 medulloblastoma.

We identify a population of Protogenin-positive (PRTG+ve) MYChigh NESTINlow stem cells in the four-week-old human embryonic hindbrain that subsequently localizes to the ventricular zone of the rhombic lip (RLVZ). Oncogenic transformation of early Prtg+ve rhombic lip stem cells initiates group 3 medulloblastoma (Gr3-MB)-like tumors. PRTG+ve stem cells grow adjacent to a human-specific interposed vascular plexus in the RLVZ, a phenotype that is recapitulated in Gr3-MB but not in other types of medulloblastoma. Co-culture of Gr3-MB with endothelial cells promotes tumor stem cell growth, with the endothelial cells adopting an immature phenotype. Targeting the PRTGhigh compartment of Gr3-MB in vivo using either the diphtheria toxin system or chimeric antigen receptor T cells constitutes effective therapy. Human Gr3-MBs likely arise from early embryonic RLVZ PRTG+ve stem cells inhabiting a specific perivascular niche. Targeting the PRTGhigh compartment and/or the perivascular niche represents an approach to treat children with Gr3-MB.

Fetal Brain-Derived Exosomal miRNAs from Maternal Blood: Potential Diagnostic Biomarkers for Fetal Alcohol Spectrum Disorders (FASDs).

Fetal alcohol spectrum disorders (FASDs) are leading causes of neurodevelopmental disability but cannot be diagnosed early in utero. Because several microRNAs (miRNAs) are implicated in other neurological and neurodevelopmental disorders, the effects of EtOH exposure on the expression of these miRNAs and their target genes and pathways were assessed. In women who drank alcohol (EtOH) during pregnancy and non-drinking controls, matched individually for fetal sex and gestational age, the levels of miRNAs in fetal brain-derived exosomes (FB-Es) isolated from the mothers' serum correlated well with the contents of the corresponding fetal brain tissues obtained after voluntary pregnancy termination. In six EtOH-exposed cases and six matched controls, the levels of fetal brain and maternal serum miRNAs were quantified on the array by qRT-PCR. In FB-Es from 10 EtOH-exposed cases and 10 controls, selected miRNAs were quantified by ddPCR. Protein levels were quantified by ELISA. There were significant EtOH-associated reductions in the expression of several miRNAs, including miR-9 and its downstream neuronal targets BDNF, REST, Synapsin, and Sonic hedgehog. In 20 paired cases, reductions in FB-E miR-9 levels correlated strongly with reductions in fetal eye diameter, a prominent feature of FASDs. Thus, FB-E miR-9 levels might serve as a biomarker to predict FASDs in at-risk fetuses.

A combination of phospholipids and long chain polyunsaturated fatty acids supports neurodevelopmental outcomes in infants: a randomized, double-blind, controlled clinical trial.

Phospholipids (PLs) and long-chain polyunsaturated fatty acids (LCPUFAs) are naturally present in breast milk and play important roles in promoting the growth of the infant. Several studies have investigated the effects of the combination of PLs and LCPUFAs on neurodevelopment. However, data on the effectiveness of infant formula containing both PLs and LCPUFAs on the neurodevelopment of infants is still scarce. This randomized, double-blind, controlled clinical study was designed to evaluate the effect of an infant formula enriched with PLs and LCPUFAs on growth parameters and neurodevelopmental outcomes in term infants up to 365 days of age. Infants were enrolled within 30 days of birth who were then randomly assigned to either a control group (n = 150) or an investigational group (n = 150). Both groups consist of cow's milk-based formula which were generally identical in terms of composition, except that the investigational formula was additionally supplemented with PLs and LCPUFAs. The infants were followed for the first year of life. Breastfed infants were the reference (n = 150). Bayley Scales of Infant Development [3rd edition (Bayley-III)], Carey Toddler Temperament Scales (TTS), MacArthur-Bates Communicative Development Inventories (CDI), Single Object Attention and Free Play Tasks were used to evaluate neurodevelopmental outcomes of infant at 365 days of age. In addition, Ages and Stages Questionnaires (ASQ) were also conducted at 120, 180, and 275 days of age. Compared to breastfeeding, both infant formulas were well-tolerated and provided adequate growth, with no adverse events being reported throughout the study. Infants of the investigational group showed higher mean scores in Bayley-III cognitive performance (104.3 vs. 99.0, p < 0.05), language (106.9 vs. 104.5, p < 0.05), and motor skills (109.2 vs. 103.9, p < 0.05) compared the control group. Similar results were being reported for other developmental scales including TTS and ASQ. Notably, the test scores of infants fed the investigational formula were similar to those who were breastfed. Our results indicate that PL and LCPUFA supplementation may be beneficial for neurodevelopment of infants throughout the first year of life. Further studies are needed to investigation long-term effects PL and LCPUFA on neurodevelopment in early life.

Socioeconomic Inequalities Affect Brain Responses of Infants Growing Up in Germany.

Developmental changes in functional neural networks are sensitive to environmental influences. This EEG study investigated how infant brain responses relate to the social context that their families live in. Event-related potentials of 255 healthy, awake infants between six and fourteen months were measured during a passive auditory oddball paradigm. Infants were presented with 200 standard tones and 48 randomly distributed deviants. All infants are part of a longitudinal study focusing on families with socioeconomic and/or cultural challenges (Bremen Initiative to Foster Early Childhood Development; BRISE; Germany). As part of their familial socioeconomic status (SES), parental level of education and infant's migration background were assessed with questionnaires. For 30.6% of the infants both parents had a low level of education (≤10 years of schooling) and for 43.1% of the infants at least one parent was born abroad. The N2-P3a complex is associated with unintentional directing of attention to deviant stimuli and was analysed in frontocentral brain regions. Age was utilised as a control variable. Our results show that tone deviations in infants trigger an immature N2-P3a complex. Contrary to studies with older children or adults, the N2 amplitude was more positive for deviants than for standards. This may be related to an immature superposition of the N2 with the P3a. For infants whose parents had no high-school degree and were born abroad, this tendency was increased, indicating that facing multiple challenges as a young family impacts on the infant's early neural development. As such, attending to unexpected stimulus changes may be important for early learning processes. Variations of the infant N2-P3a complex may, thus, relate to early changes in attentional capacity and learning experiences due to familial challenges. This points towards the importance of early prevention programs.

Placental Epigenome Impacts Fetal Development: Effects of Maternal Nutrients and Gut Microbiota.

Evidence is emerging on the role of maternal diet, gut microbiota, and other lifestyle factors in establishing lifelong health and disease, which are determined by transgenerationally inherited epigenetic modifications. Understanding epigenetic mechanisms may help identify novel biomarkers for gestation-related exposure, burden, or disease risk. Such biomarkers are essential for developing tools for the early detection of risk factors and exposure levels. It is necessary to establish an exposure threshold due to nutrient deficiencies or other environmental factors that can result in clinically relevant epigenetic alterations that modulate disease risks in the fetus. This narrative review summarizes the latest updates on the roles of maternal nutrients (n-3 fatty acids, polyphenols, vitamins) and gut microbiota on the placental epigenome and its impacts on fetal brain development. This review unravels the potential roles of the functional epigenome for targeted intervention to ensure optimal fetal brain development and its performance in later life.

Effects of pain, sedation and analgesia on neonatal brain injury and brain development.

Critically ill newborns experience numerous painful procedures as part of lifesaving care in the Neonatal Intensive Care Unit. However, painful exposures in the neonatal period have been associated with alterations in brain maturation and poorer neurodevelopmental outcomes in childhood. The most frequently used medications for pain and sedation in the NICU are opioids, benzodiazepines and sucrose; these have also been associated with abnormalities in brain maturation and neurodevelopment making it challenging to know what the best approach is to treat neonatal pain. This article provides clinicians with an overview of how neonatal exposure to pain as well as analgesic and sedative medications impact brain maturation and neurodevelopmental outcomes in critically ill infants. We also highlight areas in need of future research to develop standardized neonatal pain monitoring and management strategies.

Vitamins, minerals and their maternal levels' role in brain development: An updated literature-review.

One's neurobehavioural and mental health are built during the exact and complex process of brain development. It is thought that fetal development is where neuropsychiatric disorders first emerged. Behavioural patterns can change as a result of neuropsychiatric illnesses. The incidence is rising quickly; nevertheless, providing exceptional care remains a significant challenge for families and healthcare systems. It has been demonstrated that one of the main factors causing the transmission of these diseases is maternal exposure. Through physiologic pathways, maternal health and intrauterine exposures can affect brain development. Our attention has been focused on epigenetic factors, particularly in the gestational environment, which may be responsible for human neurodegenerative diseases since our main mental development occurs during the nine months of intrauterine life. After thoroughly searching numerous databases, this study examined the effect of fat-soluble vitamins, water-soluble vitamins, and minerals and their maternal-level effect on brain development.