Brain Development Function Research Articles

CE Workshop 03: Stroke in the Developing Brain: Mechanisms, Outcomes, and Intervention

Abstract & Learning Objectives:Over the past 10-15 years, significant progress has been made in the diagnosis and treatment of pediatrics stroke. Accordingly, the focus of much research has turned to understanding factors that determine neurological and neuropsychological outcomes in this population. This Continuing Education (CE) course will start by defining key terms in the field of pediatric stroke and reviewing current understanding of epidemiology, pathophysiology, diagnosis, and medical treatment. Next, we will review recent neuropsychological literature on cognitive outcomes following pediatric stroke, highlighting the vulnerability of the developing brain, the long-term deficits that often result from early disruption of brain function and subsequent brain development, and the significant variability in outcomes seen across individuals. Heterogeneity in outcomes has been linked to a range of clinical and demographic factors, including those related to the brain (e.g., stroke type, lesion location and size, adaptive and maladaptive patterns of reorganization), the child (e.g., age at stroke, age at assessment, comorbid neurological conditions) and the environment (family stress, parent mental health, educational support). Multi-disciplinary approaches to intervention will also be discussed. Finally, directions for future research will also be outlined, as we are just starting to understand how these factors interact to impact neurocognitive outcome and resiliency following pediatric stroke.Upon conclusion of this course, learners will be able to: 1.Describe the epidemiology, pathophysiology, and neurological outcomes associated with stroke in infants and children2.Illustrate the variability in neuropsychological outcomes after pediatric stroke and highlight important determining factors of these outcomes3.Apply current research into outcomes and treatments to neuropsychological practice

2 Effects of Early Exposure to More Than One Language in the Home on Language Skills and Brain Functional Network Organization in Young Children with Autism Spectrum Disorder

Objective:Concerns that exposure to more than one language in the home might negatively impact language development in young children with autism spectrum disorder (ASD) are common among caregivers. Although research directly examining the impact of a multilingual home environment in ASD is scarce, emerging evidence shows that language outcomes might be equivalent or better in children with ASD exposed to more than one language (Romero & Uddin, 2021). However, no evidence to date exists on whether exposure to more than one language affects early brain functional development in children with ASD. The current study aims to examine the (1) cross-sectional and (2) longitudinal associations between home language environment (exposure to one v. multiple languages at home, H1l vs. H>1l) and receptive and expressive language skills in young children with and without ASD, and (3) to investigate links between home language environment and brain functional network organization.Participants and Methods:Participants included young children with ASD (n=67, mean age: 35±13 months, H>1l n=43) and typically developing (TD) children (n=39, mean age: 32±16 months, H>1l n=17) enrolled in a longitudinal study of early brain markers of autism. A subset of children with ASD for whom longitudinal behavioral data from two study visits were available (n=21, H>1l n=11) were used for exploratory analysis. Receptive language (RL) and expressive language (EL) skills were assessed by the Mullen Scales of Early Learning at each study visit. Data from 42 children with ASD (H>1l n=27) and 38 TD children (H>1l n= 15) for whom functional MRI data were acquired during natural sleep were included in functional connectivity (FC) analysis. ANCOVAs were employed to examine the effect of diagnosis, home language environment (H1l vs. H>1l) and its interaction on RL and EL skills while controlling for socioeconomic variables (i.e., maternal education level, income-to-needs ratio) and gestational age at birth. Linear mixed models were applied to explore the longitudinal effect of home language environment on RL and EL skills across two study visits in the ASD group. Lastly, FC analysis was conducted to compare functional connectivity across 7 canonical brain networks in children with and without ASD who were raised in H1l and H>1l.Results:We found significant diagnosis by home language environment interaction effect on EL skills, with children with ASD and H1l exhibiting the lowest EL skills. Longitudinal analysis identified a significant home language environment by study visit interaction effect on EL skills in children with ASD. Specifically, children with ASD and H1l showed lower EL skills at study visit 1 but equivalent EL skills at study visit 2 compared to children with ASD and H>1l. FC analysis revealed that children with ASD and H>1l displayed more typical brain network organization (similar to TD children) compared to those with H1l, specifically for FC between language, frontoparietal, and default mode networks.Conclusions:These results suggest that early exposure to more than one language in the home may be linked with better expressive language skills in young children with ASD. Results of functional connectivity analysis also suggest that exposure to more than one language may be associated with more neurotypical functional network organization, particularly involving language and high-order networks.

Developmental changes in endogenous testosterone have sexually-dimorphic effects on spontaneous cortical dynamics.

The transition from childhood to adolescence is associated with an influx of sex hormones, which not only facilitates physical and behavioral changes, but also dramatic changes in neural circuitry. While previous work has shown that pubertal hormones modulate structural and functional brain development, few of these studies have focused on the impact that such hormones have on spontaneous cortical activity, and whether these effects are modulated by sex during this critical developmental window. Herein, we examined the effect of endogenous testosterone on spontaneous cortical activity in 71 typically-developing youth (ages 10-17 years; 32 male). Participants completed a resting-state magnetoencephalographic (MEG) recording, structural MRI, and provided a saliva sample for hormone analysis. MEG data were source-reconstructed and the power within five canonical frequency bands (delta, theta, alpha, beta, and gamma) was computed. The resulting power spectral density maps were analyzed via vertex-wise ANCOVAs to identify spatially specific effects of testosterone and sex by testosterone interactions, while covarying out age. We found robust sex differences in the modulatory effects of testosterone on spontaneous delta, beta, and gamma activity. These interactions were largely confined to frontal cortices and exhibited a stark switch in the directionality of the correlation from the low (delta) to high frequencies (beta/gamma). For example, in the delta band, greater testosterone related to lower relative power in prefrontal cortices in boys, while the reverse pattern was found for girls. These data suggest testosterone levels are uniquely related to the development of spontaneous cortical dynamics during adolescence, and such levels are associated with different developmental patterns in males and females within regions implicated in executive functioning.

PENGARUH PENERAPAN PIJAT BAYI (BABY MASSAGE) TERHADP KUANTITAS TIDUR BAYI USIA 3 -12 BULAN DI PMB AFITA DELIANAH TUREN

Sleep quantity is a measure by which a person can easily initiate sleep and maintain sleep.Introduction: The effectiveness of baby massage on sleep quantity was influenced by increase in catecholamine hormone that trigger growth and development stimulations, increase appetite, increase body weight, increase sleep quality and quantity, and stimulate brain structure and function development. Objective of the research was to determinw effects of applying a baby massage to quantity of sleep for babies aged 3- 12 months at PMB Afita Delianah Turen. Methods: researcher applied one group pretest and posttest approaches. This research sample was 15 infants aged 3- 12month in accordance with inclusion criteria. In collecting technique applied SOP baby massage and observation sheets. Results: Using wilcoxson Analysis Test that acquiring significant values of 0. 000< (0. 05). Conclusion: There is effects of a baby massage application on sleep quantity of babies aged 3- 12months at PMB Afita Delianah Turen. It is recommended that mothers who have babies with sleep quantity disorders can be overcome with Baby Massage.

Interneuron odyssey: molecular mechanisms of tangential migration.

Cortical GABAergic interneurons are critical components of neural networks. They provide local and long-range inhibition and help coordinate network activities involved in various brain functions, including signal processing, learning, memory and adaptative responses. Disruption of cortical GABAergic interneuron migration thus induces profound deficits in neural network organization and function, and results in a variety of neurodevelopmental and neuropsychiatric disorders including epilepsy, intellectual disability, autism spectrum disorders and schizophrenia. It is thus of paramount importance to elucidate the specific mechanisms that govern the migration of interneurons to clarify some of the underlying disease mechanisms. GABAergic interneurons destined to populate the cortex arise from multipotent ventral progenitor cells located in the ganglionic eminences and pre-optic area. Post-mitotic interneurons exit their place of origin in the ventral forebrain and migrate dorsally using defined migratory streams to reach the cortical plate, which they enter through radial migration before dispersing to settle in their final laminar allocation. While migrating, cortical interneurons constantly change their morphology through the dynamic remodeling of actomyosin and microtubule cytoskeleton as they detect and integrate extracellular guidance cues generated by neuronal and non-neuronal sources distributed along their migratory routes. These processes ensure proper distribution of GABAergic interneurons across cortical areas and lamina, supporting the development of adequate network connectivity and brain function. This short review summarizes current knowledge on the cellular and molecular mechanisms controlling cortical GABAergic interneuron migration, with a focus on tangential migration, and addresses potential avenues for cell-based interneuron progenitor transplants in the treatment of neurodevelopmental disorders and epilepsy.

Lamb-Shaffer syndrome: 20 Spanish patients and literature review expands the view of neurodevelopmental disorders caused by SOX5 haploinsufficiency.

Lamb-Shaffer Syndrome (LSS; OMIM #616803; ORPHA #313892; ORPHA #313884) is an infrequent genetic disorder that affects multiple aspects of human development especially those related to the development of the nervous system. LSS is caused by variants in the SOX5 gene. At the molecular level, SOX5 gene encodes for a transcription factor containing a High Mobility Group (HMG) DNA-Binding domain with relevant functions in brain development in different vertebrate species. Clinical features of Lamb-Shaffer syndrome may include intellectual disability, delayed speech and language development, attention deficits, hyperactivity, autism spectrum disorder, visual problems and seizures. Additionally, patients with the syndrome may present distinct facial dimorphism such as a wide mouth with full lips, small chin, broad nasal bridge, and deep-set eyes. Other physical features that have been reported in some patients include short stature, scoliosis, and joint hypermobility. Here, we report the clinical and molecular characterization of a Spanish LSS cohort of new 20 patients and review all the patients published so far which amount for 111 patients. The most frequent features included developmental delay, intellectual disability, visual problems, poor speech development and facial dysmorphic features. Strikingly, pain insensitivity and hypermetropia seems to be more frequent than previously reported, based on the frequency seen in the Spanish cohort. Eighty-three variants have been reported so far, single nucleotide variants (SNV) and copy number variants represent 47% and 53%, respectively, from the total of variants reported. Similarly to previous reports, the majority of the SNVs variants of the novel patients reported herein fall in the HMG domain of the protein. However, new variants, affecting other functional domains, were also detected. In conclusion, LLS is a rare genetic disorder mostly characterized by a wide range of developmental and neurological symptoms. Early diagnosis would allow to start of care programs, clinical follow up, prospective studies and appropriate genetic counseling, to promote clinical and social improvement to have profound lifelong benefits for patients and their families. Further research is needed to better understand the underlying mechanisms of the syndrome related to SOX5 haploinsufficiency.

Lactate Metabolism, Signaling, and Function in Brain Development, Synaptic Plasticity, Angiogenesis, and Neurodegenerative Diseases.

Neural tissue requires a great metabolic demand despite negligible intrinsic energy stores. As a result, the central nervous system (CNS) depends upon a continuous influx of metabolic substrates from the blood. Disruption of this process can lead to impairment of neurological functions, loss of consciousness, and coma within minutes. Intricate neurovascular networks permit both spatially and temporally appropriate metabolic substrate delivery. Lactate is the end product of anaerobic or aerobic glycolysis, converted from pyruvate by lactate dehydrogenase-5 (LDH-5). Although abundant in the brain, it was traditionally considered a byproduct or waste of glycolysis. However, recent evidence indicates lactate may be an important energy source as well as a metabolic signaling molecule for the brain and astrocytes-the most abundant glial cell-playing a crucial role in energy delivery, storage, production, and utilization. The astrocyte-neuron lactate-shuttle hypothesis states that lactate, once released into the extracellular space by astrocytes, can be up-taken and metabolized by neurons. This review focuses on this hypothesis, highlighting lactate's emerging role in the brain, with particular emphasis on its role during development, synaptic plasticity, angiogenesis, and disease.

Brain-specific Pd1 deficiency leads to cortical neurogenesis defects and depressive-like behaviors in mice.

Embryonic neurogenesis is tightly regulated by multiple factors to ensure the precise development of the cortex. Deficiency in neurogenesis may result in behavioral abnormalities. Pd1 is a well-known inhibitory immune molecule, but its function in brain development remains unknown. Here, we find brain specific deletion of Pd1 results in abnormal cortical neurogenesis, including enhanced proliferation of neural progenitors and reduced neuronal differentiation. In addition, neurons in Pd1 knockout mice exhibit abnormal morphology, both the total length and the number of primary dendrites were reduced. Moreover, Pd1cKO mice exhibit depressive-like behaviors, including immobility, despair, and anhedonia. Mechanistically, Pd1 regulates embryonic neurogenesis by targeting Pax3 through the β-catenin signaling pathway. The constitutive expression of Pax3 partly rescues the deficiency of neurogenesis in the Pd1 deleted embryonic brain. Besides, the administration of β-catenin inhibitor, XAV939, not only rescues abnormal brain development but also ameliorates depressive-like behaviors in Pd1cKO mice. Simultaneously, Pd1 plays a similar role in human neural progenitor cells (hNPCs) proliferation and differentiation. Taken together, our findings reveal the critical role and regulatory mechanism of Pd1 in embryonic neurogenesis and behavioral modulation, which could contribute to understanding immune molecules in brain development.

Profiling intra- and inter-individual differences in brain development across early adolescence

As we move toward population-level developmental neuroscience, understanding intra- and inter-individual variability in brain maturation and sources of neurodevelopmental heterogeneity becomes paramount. Large-scale, longitudinal neuroimaging studies have uncovered group-level neurodevelopmental trajectories, and while recent work has begun to untangle intra- and inter-individual differences, they remain largely unclear. Here, we aim to quantify both intra- and inter-individual variability across facets of neurodevelopment across early adolescence (ages 8.92 to 13.83 years) in the Adolescent Brain Cognitive Development (ABCD) Study and examine inter-individual variability as a function of age, sex, and puberty. Our results provide novel insight into differences in annualized percent change in macrostructure, microstructure, and functional brain development from ages 9–13 years old. These findings reveal moderate age-related intra-individual change, but age-related differences in inter-individual variability only in a few measures of cortical macro- and microstructure development. Greater inter-individual variability in brain development were seen in mid-pubertal individuals, except for a few aspects of white matter development that were more variable between prepubertal individuals in some tracts. Although both sexes contributed to inter-individual differences in macrostructure and functional development in a few regions of the brain, we found limited support for hypotheses regarding greater male-than-female variability. This work highlights pockets of individual variability across facets of early adolescent brain development, while also highlighting regional differences in heterogeneity to facilitate future investigations in quantifying and probing nuances in normative development, and deviations therefrom.

Fine-grained functional parcellation maps of the infant cerebral cortex.

Resting-state functional MRI (rs-fMRI) is widely used to examine the dynamic brain functional development of infants, but these studies typically require precise cortical parcellation maps, which cannot be directly borrowed from adult-based functional parcellation maps due to the substantial differences in functional brain organization between infants and adults. Creating infant-specific cortical parcellation maps is thus highly desired but remains challenging due to difficulties in acquiring and processing infant brain MRIs. In this study, we leveraged 1064 high-resolution longitudinal rs-fMRIs from 197 typically developing infants and toddlers from birth to 24 months who participated in the Baby Connectome Project to develop the first set of infant-specific, fine-grained, surface-based cortical functional parcellation maps. To establish meaningful cortical functional correspondence across individuals, we performed cortical co-registration using both the cortical folding geometric features and the local gradient of functional connectivity (FC). Then we generated both age-related and age-independent cortical parcellation maps with over 800 fine-grained parcels during infancy based on aligned and averaged local gradient maps of FC across individuals. These parcellation maps reveal complex functional developmental patterns, such as changes in local gradient, network size, and local efficiency, especially during the first 9 postnatal months. Our generated fine-grained infant cortical functional parcellation maps are publicly available at https://www.nitrc.org/projects/infantsurfatlas/ for advancing the pediatric neuroimaging field.

Martin-Bell fragile X syndrome

Fragile X syndrome (FXS) is one of the many disorders that are known and that are caused by some alteration or modification at the genetic level, one of the main characteristics of this type of syndrome also called Martin-Bell syndrome, is intellectual disability, as well as certain behaviors due to behavioral disorders, This is due to changes in the FMR1 gene, which is very important because it is responsible for producing the FMRP protein, which has the function of brain development, so when there is some kind of change in the gene and developing FXS the person may have little or no production of the FMRP protein.

Functional MRI responses to naturalistic stimuli are increasingly typical across early childhood

While findings show that throughout development, there are child- and age-specific patterns of brain functioning, there is also evidence for significantly greater inter-individual response variability in young children relative to adults. It is currently unclear whether this increase in functional “typicality” (i.e., inter-individual similarity) is a developmental process that occurs across early childhood, and what changes in BOLD response may be driving changes in typicality. We collected fMRI data from 81 typically developing 4–8-year-old children during passive viewing of age-appropriate television clips and asked whether there is increasing typicality of brain response across this age range. We found that the “increasing typicality” hypothesis was supported across many regions engaged by passive viewing. Post hoc analyses showed that in a priori ROIs related to language and face processing, the strength of the group-average shared component of activity increased with age, with no concomitant decline in residual signal or change in spatial extent or variability. Together, this suggests that increasing inter-individual similarity of functional responses to audiovisual stimuli is an important feature of early childhood functional brain development.

Upregulation of A-type potassium channels suppresses neuronal excitability in hypoxic neonatal mice.

Neuronal excitability is a critical feature of central nervous system development, playing a fundamental role in the functional maturation of brain regions, including the hippocampus, cerebellum, auditory and visual systems. The present study aimed to determine the mechanism by which hypoxia causes brain dysfunction through perturbation of neuronal excitability in a hypoxic neonatal mouse model. Functional brain development was assessed in humans using the Gesell Development Diagnosis Scale. In mice, gene transcription was evaluated via mRNA sequencing and quantitative PCR; furthermore, patch clamp recordings assessed potassium currents. Clinical observations revealed disrupted functional brain development in 6- and 18-month-old hypoxic neonates, and those born with normal hearing screening unexpectedly exhibited impaired central auditory function at 3 months. In model mice, CA1 pyramidal neurons exhibited reduced spontaneous activity, largely induced by excitatory synaptic input suppression, despite the elevated membrane excitability of hypoxic neurons compared to that of control neurons. In hypoxic neurons, Kcnd3 gene transcription was upregulated, confirming upregulated hippocampal Kv 4.3 expression. A-type potassium currents were enhanced, and Kv 4.3 participated in blocking excitatory presynaptic inputs. Elevated Kv 4.3 activity in pyramidal neurons under hypoxic conditions inhibited excitatory presynaptic inputs and further decreased neuronal excitability, disrupting functional brain development in hypoxic neonates.

Changes in brain metabolite levels across childhood

Metabolites play important roles in brain development and their levels change rapidly in the prenatal period and during infancy. Metabolite levels are thought to stabilize during childhood, but the development of neurochemistry across early-middle childhood remains understudied. We examined the developmental changes of key metabolites (total N-acetylaspartate, tNAA; total choline, tCho; total creatine, tCr; glutamate+glutamine, Glx; and myo-inositol, mI) using short echo-time magnetic resonance spectroscopy (MRS) in the anterior cingulate cortex (ACC) and the left temporo-parietal cortex (LTP) using a mixed cross-sectional/longitudinal design in children aged 2–11 years (ACC: N = 101 children, 112 observations; LTP: N = 95 children, 318 observations). We found that tNAA increased with age in both regions, while tCho decreased with age in both regions. tCr increased with age in the LTP only. Glx did not show linear age effects in either region, but a follow-up analysis in participants with ≥3 datapoints in the LTP revealed a quadratic effect of age following an inverted U-shape. These substantial changes in neurochemistry throughout childhood likely underlie various processes of structural and functional brain development.

A STUDY ON VARIED PSYCHOLOGICAL DYNAMICS OF HUMAN LIFE

Psychology is the study of the mind and behaviour. Psychologists look into the many dimensions of being a person, including thoughts, brain function, activities, emotions, personality, and human development. Human society is always evolving, and he is the most intelligent creature on the planet. Humans act differently depending on the demands of the circumstance. Every person is unique, and their behaviour depends on a variety of psychological elements like their intelligence, emotional maturity, motivation, ability to adapt, self-concept, self-efficacy, and susceptibility to depression, anxiety, and stress. The purpose of the current study is to discuss the many psychological dynamics that affect human personality and character and in broader sense human life a lot. KEYWORDS: depression, anxiety, stress, emotional intelligence, emotional maturity, creativity, motivation, adjustment, self-concept, and self-efficacy.

Competitive, multi-objective, and compartmented Flux Balance Analysis for addressing tissue-specific inborn errors of metabolism.

The inborn error of metabolism phenylketonuria (PKU, OMIM 261600) is most often due to inactivation of phenylalanine hydroxylase (PAH), which converts phenylalanine (Phe) into tyrosine (Tyr). The reduced PAH activity increases blood concentration of phenylalanine and urine levels of phenylpyruvate. Flux balance analysis (FBA) of a single-compartment model of PKU predicts that maximum growth rate should be reduced unless Tyr is supplemented. However, the PKU phenotype is lack of development of brain function specifically, and Phe reduction rather than Tyr supplementation cures the disease. Phe and Tyr cross the blood-brain barrier (BBB) through the aromatic amino acid transporter implying that the two transport reactions interact. However, FBA does not accommodate such competitive interactions. We here report on an extension to FBA that enables it to deal with such interactions. We built a three-compartment model, made the common transport across the BBB explicit, and included dopamine and serotonin synthesis as parts of the brain function to be delivered by FBA. With these ramifications, FBA of the genome-scale metabolic model extended to three compartments does explain that (i) the disease is brain specific, (ii) phenylpyruvate in urine is a biomarker, (iii) excess of blood-phenylalanine rather than shortage of blood-tyrosine causes brain pathology, and (iv) Phe deprivation is the better therapy. The new approach also suggests (v) explanations for differences in pathology between individuals with the same PAH inactivation, and (vi) interference of disease and therapy with the functioning of other neurotransmitters.

Adolescents' Social Media Use May Affect Functional Brain Development.

According to this study: Constant checking of social media during early adolescence may be associated with changes in the brain's sensitivity to potential social rewards and punishments.

Multifaceted microglia during brain development: Models and tools.

Microglia, the brain resident macrophages, are multifaceted glial cells that belong to the central nervous and immune systems. As part of the immune system, they mediate innate immune responses, regulate brain homeostasis and protect the brain in response to inflammation or injury. At the same time, they can perform a wide array of cellular functions that relate to the normal functioning of the brain. Importantly, microglia are key actors of brain development. Indeed, these early brain invaders originate outside of the central nervous system from yolk sac myeloid progenitors, and migrate into the neural folds during early embryogenesis. Before the generation of oligodendrocytes and astrocytes, microglia thus occupy a unique position, constituting the main glial population during early development and participating in a wide array of embryonic and postnatal processes. During this developmental time window, microglia display remarkable features, being highly heterogeneous in time, space, morphology and transcriptional states. Although tremendous progress has been made in our understanding of their ontogeny and roles, there are several limitations for the investigation of specific microglial functions as well as their heterogeneity during development. This review summarizes the current murine tools and models used in the field to study the development of these peculiar cells. In particular, we focus on the methodologies used to label and deplete microglia, monitor their behavior through live-imaging and also discuss the progress currently being made by the community to unravel microglial functions in brain development and disorders.

The Application of Mind Mapping to English Vocabulary Teaching in Senior High School

Mind mapping is a tool for radioactive thinking using images and associations. It has the characteristics of visibility, divergence, radioactivity and multi-dimension. It is a popular revolutionary thinking tool in the 21st century. It was developed in the 1970s by Tony Buzan. This method is famous for inducing the development of left and right brain functions, and making it concrete by assisting memory with shapes, colors and symbols. It has far-reaching influence in many fields. At present, there are still some problems in English vocabulary teaching in China. What’s more, mind mapping is rarely widely used in vocabulary teaching. Therefore, this paper aims to explain how to use mind mapping to help solve the current problems of students' vocabulary.

Brain imaging and morphological plasticity in glioblastoma: a literature review.

This article provides a comprehensive review of the role of functional magnetic resonance imaging (fMRI) in characterizing neural plasticity in glioblastoma patients. Glioblastoma, the most common primary brain tumor, has a rapid growth rate and infiltrative nature that leads to the disorganization of the normal brain network. Neuroplasticity, still not fully understood, is the foundation for the development of brain functions during the growth and recovery of certain brain functions after a brain lesion such as a tumor, trauma, or vascular event. Functional MRI has the capacity to identify the regions that activate at rest or when performing a task. It can determine the extent to which these regions, responsible for a specific function, are impacted by a tumor and eventually after surgical excision. Likewise, it can help evaluate to which extent activation changes when recovery of function occurs. In this article, we aimed to understand the significance of fMRI in the management of glioblastoma by analyzing representative articles from the literature.