Plasticity during Early Brain Development Is Determined by Ontogenetic Potential.
Krägeloh-Mann, Ingeborg; Lidzba, Karen; Pavlova, Marina A; Wilke, Marko; Staudt, Martin
2017-04-01
Two competing hypotheses address neuroplasticity during early brain development: the "Kennard principle" describes the compensatory capacities of the immature developing CNS as superior to those of the adult brain, whereas the "Hebb principle" argues that the young brain is especially sensitive to insults. We provide evidence that these principles are not mutually exclusive. Following early brain lesions that are unilateral, the brain can refer to homotopic areas of the healthy hemisphere. This potential for reorganization is unique to the young brain but available only when, during ontogenesis of brain development, these areas have been used for the functions addressed. With respect to motor function, ipsilateral motor tracts can be recruited, which are only available during early brain development. Language can be reorganized to the right after early left hemispheric lesions, as the representation of the language network is initially bilateral. However, even in these situations, compensatory capacities of the developing brain are found to have limitations, probably defined by early determinants. Thus, plasticity and adaptivity are seen only within ontogenetic potential; that is, axonal or cortical structures cannot be recruited beyond early developmental possibilities. The young brain is probably more sensitive and vulnerable to lesions when these are bilateral. This is shown here for bilateral periventricular white matter lesions that clearly have an impact on cortical architecture and function, thus probably interfering with early network building. Georg Thieme Verlag KG Stuttgart · New York.
Starting Smart: How Early Experiences Affect Brain Development. An Ounce of Prevention Fund Paper.
ERIC Educational Resources Information Center
Ounce of Prevention Fund.
Recent research has provided great insight into the impact of early experience on brain development. It is now believed that brain growth is highly dependent upon early experiences. Neurons allow communication and coordinated functioning among various brain areas. Brain development after birth consists of an ongoing process of wiring and rewiring…
Early Development and the Brain: Teaching Resources for Educators
ERIC Educational Resources Information Center
Gilkerson, Linda, Ed.; Klein, Rebecca, Ed.
2008-01-01
This nine-unit curriculum translates current scientific research on early brain development into practical suggestions to help early childhood professionals understand the reciprocal link between caregiving and brain development. The curriculum was created and extensively field-tested by the Erikson Institute Faculty Development Project on the…
... All Early Learning Child Care Early Literacy Early Math and Science Language and Communication Play School Readiness ... Brain Development from Birth Series Let's Talk About Math: Early Math Video Series Resource | Disponible en español ...
How the Timing and Quality of Early Experiences Influence the Development of Brain Architecture
Fox, Sharon E.; Levitt, Pat; Nelson, Charles A.
2009-01-01
Early life events can exert a powerful influence on both the pattern of brain architecture and behavioral development. In this paper a conceptual framework is provided for considering how the structure of early experience gets “under the skin.” The paper begins with a description of the genetic framework that lays the foundation for brain development, and then to the ways experience interacts with and modifies the structures and functions of the developing brain. Much of the attention is focused on early experience and sensitive periods, although it is made clear that later experience also plays an important role in maintaining and elaborating this early wiring diagram, which is critical to establishing a solid footing for development beyond the early years. PMID:20331653
Why Should I Read to My Baby? The Importance of Early Literacy
ERIC Educational Resources Information Center
High, Pamela C.
2013-01-01
"Early Brain and Child Development" as a strategic priority of the American Academy of Pediatrics recognizes that early literacy and language skills build a strong foundation for healthy development and academic success. Promoting early literacy in the context of pediatric primary care supports early brain development and positive,…
ERIC Educational Resources Information Center
Edie, David; Schmid, Deborah
2007-01-01
For decades researchers have been aware of the extraordinary development of a child's brain during the first five years of life. Recent advances in neuroscience have helped crystallize earlier findings, bringing new clarity and understanding to the field of early childhood brain development. Children are born ready to learn. They cultivate 85…
Development of a Human Neurovascular Unit Organotypic Systems Model of Early Brain Development
The inability to model human brain and blood-brain barrier development in vitro poses a major challenge in studies of how chemicals impact early neurogenic periods. During human development, disruption of thyroid hormone (TH) signaling is related to adverse morphological effects ...
Dubois, J; Dehaene-Lambertz, G; Kulikova, S; Poupon, C; Hüppi, P S; Hertz-Pannier, L
2014-09-12
Studying how the healthy human brain develops is important to understand early pathological mechanisms and to assess the influence of fetal or perinatal events on later life. Brain development relies on complex and intermingled mechanisms especially during gestation and first post-natal months, with intense interactions between genetic, epigenetic and environmental factors. Although the baby's brain is organized early on, it is not a miniature adult brain: regional brain changes are asynchronous and protracted, i.e. sensory-motor regions develop early and quickly, whereas associative regions develop later and slowly over decades. Concurrently, the infant/child gradually achieves new performances, but how brain maturation relates to changes in behavior is poorly understood, requiring non-invasive in vivo imaging studies such as magnetic resonance imaging (MRI). Two main processes of early white matter development are reviewed: (1) establishment of connections between brain regions within functional networks, leading to adult-like organization during the last trimester of gestation, (2) maturation (myelination) of these connections during infancy to provide efficient transfers of information. Current knowledge from post-mortem descriptions and in vivo MRI studies is summed up, focusing on T1- and T2-weighted imaging, diffusion tensor imaging, and quantitative mapping of T1/T2 relaxation times, myelin water fraction and magnetization transfer ratio. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.
Starting Smart: How Early Experiences Affect Brain Development. Second Edition.
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Hawley, Theresa
Based on recent research, it is now believed that brain growth is highly dependent upon children's early experiences. Neurons allow communication and coordinated functioning among various brain areas. Brain development after birth consists of an ongoing process of wiring and rewiring the connections among neurons. The forming and breaking of…
Accelerated recruitment of new brain development genes into the human genome.
Zhang, Yong E; Landback, Patrick; Vibranovski, Maria D; Long, Manyuan
2011-10-01
How the human brain evolved has attracted tremendous interests for decades. Motivated by case studies of primate-specific genes implicated in brain function, we examined whether or not the young genes, those emerging genome-wide in the lineages specific to the primates or rodents, showed distinct spatial and temporal patterns of transcription compared to old genes, which had existed before primate and rodent split. We found consistent patterns across different sources of expression data: there is a significantly larger proportion of young genes expressed in the fetal or infant brain of humans than in mouse, and more young genes in humans have expression biased toward early developing brains than old genes. Most of these young genes are expressed in the evolutionarily newest part of human brain, the neocortex. Remarkably, we also identified a number of human-specific genes which are expressed in the prefrontal cortex, which is implicated in complex cognitive behaviors. The young genes upregulated in the early developing human brain play diverse functional roles, with a significant enrichment of transcription factors. Genes originating from different mechanisms show a similar expression bias in the developing brain. Moreover, we found that the young genes upregulated in early brain development showed rapid protein evolution compared to old genes also expressed in the fetal brain. Strikingly, genes expressed in the neocortex arose soon after its morphological origin. These four lines of evidence suggest that positive selection for brain function may have contributed to the origination of young genes expressed in the developing brain. These data demonstrate a striking recruitment of new genes into the early development of the human brain.
Early Influences on Brain Architecture: An Interview with Neuroscientist Eric Knudsen. Perspectives
ERIC Educational Resources Information Center
National Scientific Council on the Developing Child, 2006
2006-01-01
Early experience has a powerful and lasting influence on how the brain develops. The physical and chemical conditions that encourage the building of a strong, adaptive brain architecture are present early in life. As brains age, a number of changes lock in the ways information is processed, making it more difficult for the brain to change to other…
Graph theoretical modeling of baby brain networks.
Zhao, Tengda; Xu, Yuehua; He, Yong
2018-06-12
The human brain undergoes explosive growth during the prenatal period and the first few postnatal years, establishing an early infrastructure for the later development of behaviors and cognitions. Revealing the developmental rules during the early phrase is essential in understanding the emergence of brain function and the origin of developmental disorders. The graph-theoretical network modeling in combination with multiple neuroimaging probes provides an important research framework to explore early development of the topological wiring and organizational paradigms of the brain. Here, we reviewed studies which employed neuroimaging and graph-theoretical modeling to investigate brain network development from approximately 20 gestational weeks to 2 years of age. Specifically, the structural and functional brain networks have evolved to highly efficient topological architectures in the early stage; where the structural network remains ahead and paves the way for the development of functional network. The brain network develops in a heterogeneous order, from primary to higher-order systems and from a tendency of network segregation to network integration in the prenatal and postnatal periods. The early brain network topologies show abilities in predicting certain cognitive and behavior performance in later life, and their impairments are likely to continue into childhood and even adulthood. These macroscopic topological changes are found to be associated with possible microstructural maturations, such as axonal growth and myelinations. Collectively, this review provides a detailed delineation of the early changes of the baby brains in the graph-theoretical modeling framework, which opens up a new avenue to understand the developmental principles of the connectome. Copyright © 2018. Published by Elsevier Inc.
Research Review: Cholinergic Mechanisms, Early Brain Development, and Risk for Schizophrenia
ERIC Educational Resources Information Center
Ross, Randal G.; Stevens, Karen E.; Proctor, William R.; Leonard, Sherry; Kisley, Michael A.; Hunter, Sharon K.; Freedman, Robert; Adams, Catherine E.
2010-01-01
The onset of diagnostic symptomology for neuropsychiatric diseases is often the end result of a decades-long process of aberrant brain development. Identification of novel treatment strategies aimed at normalizing early brain development and preventing mental illness should be a major therapeutic goal. However, there are few models for how this…
Effects of Experience on the Brain: The Role of Neuroscience in Early Development and Education
ERIC Educational Resources Information Center
Twardosz, Sandra
2012-01-01
Research Findings: Research on the effect of experience on the structure and function of the brain across the lifespan pertains directly to the concerns of professionals involved with children's early development and education. This paper briefly reviews (a) the role of experience in shaping the developing brain, (b) individual adaptation to the…
Early Brain and Child Development: Connections to Early Education and Child Care
ERIC Educational Resources Information Center
Romano, Judith T.
2013-01-01
The vast majority of young children spend time in settings outside of the home, and the nature of those settings directly impacts the child's health and development. The ecobiodevelopmental framework of early brain and child development serve as the backdrop for establishing quality. This article describes the use of quality rating systems,…
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Pennsylvania Partnerships for Children, Harrisburg.
This Kids Count special report examines brain development during infancy and early childhood in order to provide a basis for an informed discussion about the need for preventive programs to foster healthy child development. The report summarizes information on early brain development and how experience shapes neural connections. It focuses on the…
ERIC Educational Resources Information Center
Eliot, Lise
2001-01-01
Discusses the connection between brain development and human educational needs based on neuroscience research. Considers brain development from conception, including cell structure, myelination, and regional development of the brain, stressing the importance of a child's early environment and the prenatal vulnerability of the brain. (JPB)
Growth and development of the brain and impact on cognitive outcomes.
Hüppi, Petra S
2010-01-01
Understanding human brain development from the fetal life to adulthood is of great clinical importance as many neurological and neurobehavioral disorders have their origin in early structural and functional cerebral maturation. The developing brain is particularly prone to being affected by endogenous and exogenous events through the fetal and early postnatal life. The concept of 'developmental plasticity or disruption of the developmental program' summarizes these events. Increases in white matter, which speed up communication between brain cells, growing complexity of neuronal networks suggested by gray and white matter changes, and environmentally sensitive plasticity are all essential aspects in a child's ability to mentalize and maintain the adaptive flexibility necessary for achieving high sociocognitive functioning. Advancement in neuroimaging has opened up new ways for examining the developing human brain in vivo, the study of the effects of early antenatal, perinatal and neonatal events on later structural and functional brain development resulting in developmental disabilities or developmental resilience. In this review, methods of quantitative assessment of human brain development, such as 3D-MRI with image segmentation, diffusion tensor imaging to assess connectivity and functional MRI to visualize brain function will be presented. Copyright (c) 2010 S. Karger AG, Basel.
Cai, Lin; Dong, Qi; Niu, Haijing
2018-04-01
Early childhood (7-8 years old) and early adolescence (11-12 years old) constitute two landmark developmental stages that comprise considerable changes in neural cognition. However, very limited information from functional neuroimaging studies exists on the functional topological configuration of the human brain during specific developmental periods. In the present study, we utilized continuous resting-state functional near-infrared spectroscopy (rs-fNIRS) imaging data to examine topological changes in network organization during development from early childhood and early adolescence to adulthood. Our results showed that the properties of small-worldness and modularity were not significantly different across development, demonstrating the developmental maturity of important functional brain organization in early childhood. Intriguingly, young children had a significantly lower global efficiency than early adolescents and adults, which revealed that the integration of the distributed networks strengthens across the developmental stages underlying cognitive development. Moreover, local efficiency of young children and adolescents was significantly lower than that of adults, while there was no difference between these two younger groups. This finding demonstrated that functional segregation remained relatively steady from early childhood to early adolescence, and the brain in these developmental periods possesses no optimal network configuration. Furthermore, we found heterogeneous developmental patterns in the regional nodal properties in various brain regions, such as linear increased nodal properties in the frontal cortex, indicating increasing cognitive capacity over development. Collectively, our results demonstrated that significant topological changes in functional network organization occurred during these two critical developmental stages, and provided a novel insight into elucidating subtle changes in brain functional networks across development. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.
Brain Development and Its Relationship to Early Childhood Education.
ERIC Educational Resources Information Center
Slegers, Brenda
New research on brain development has profound implications in the areas of child development and education. This review of the research describes how the brain develops to shape children's growing intelligence, addressing such questions as: (1) What are the brain's functions? (2) What are the critical or sensitive periods in brain development?…
ERIC Educational Resources Information Center
Bailey, Donald B., Jr., Ed.; Bruer, John T., Ed.; Symons, Frank J., Ed.; Lichtman, Jeff W., Ed.
The concept of critical or sensitive periods in child development provides an example around which to organize discussion of what is known and not known about brain development and the implications of brain science on early childhood policy and practice. This book reviews the early history of critical periods and evidence for their existence in…
Early Exposure to Toxic Substances Damages Brain Architecture. Working Paper #4
ERIC Educational Resources Information Center
National Scientific Council on the Developing Child, 2006
2006-01-01
New science shows that exposure to toxins prenatally or early in life can have a devastating and lifelong effect on the developing architecture of the brain. Exposures to many chemicals have much more severe consequences for embryos, fetuses, and young children, whose brains are still developing, than for adults. Substances that can have a truly…
Plasticity following early-life brain injury: Insights from quantitative MRI.
Fiori, Simona; Guzzetta, Andrea
2015-03-01
Over the last decade, the application of novel advanced neuroimaging techniques to study congenital brain damage has provided invaluable insights into the mechanisms underlying early neuroplasticity. The concept that is clearly emerging, both from human and nun-human studies, is that functional reorganization in the immature brain is substantially different from that of the more mature, developed brain. This applies to the reorganization of language, the sensorimotor system, and the visual system. The rapid implementation and development of higher order imaging methods will offer increased, currently unavailable knowledge about the specific mechanisms of cerebral plasticity in infancy, which is essential to support the development of early therapeutic interventions aimed at supporting and enhancing functional reorganization during a time of greatest potential brain plasticity. Copyright © 2015. Published by Elsevier Inc.
A review on neuroimaging studies of genetic and environmental influences on early brain development.
Gao, Wei; Grewen, Karen; Knickmeyer, Rebecca C; Qiu, Anqi; Salzwedel, Andrew; Lin, Weili; Gilmore, John H
2018-04-16
The past decades witnessed a surge of interest in neuroimaging study of normal and abnormal early brain development. Structural and functional studies of normal early brain development revealed massive structural maturation as well as sequential, coordinated, and hierarchical emergence of functional networks during the infancy period, providing a great foundation for the investigation of abnormal early brain development mechanisms. Indeed, studies of altered brain development associated with either genetic or environmental risks emerged and thrived. In this paper, we will review selected studies of genetic and environmental risks that have been relatively more extensively investigated-familial risks, candidate risk genes, and genome-wide association studies (GWAS) on the genetic side; maternal mood disorders and prenatal drug exposures on the environmental side. Emerging studies on environment-gene interactions will also be reviewed. Our goal was not to perform an exhaustive review of all studies in the field but to leverage some representative ones to summarize the current state, point out potential limitations, and elicit discussions on important future directions. Copyright © 2018 Elsevier Inc. All rights reserved.
Evaluation of Disease Lesions in the Developing Canine MPS IIIA Brain.
Winner, Leanne K; Marshall, Neil R; Jolly, Robert D; Trim, Paul J; Duplock, Stephen K; Snel, Marten F; Hemsley, Kim M
2018-06-20
Mucopolysaccharidosis IIIA (MPS IIIA) is an inherited neurodegenerative disease of childhood that results in early death. Post-mortem studies have been carried out on human MPS IIIA brain, but little is known about early disease development. Here, we utilised the Huntaway dog model of MPS IIIA to evaluate disease lesion development from 2 to 24 weeks of age. A significant elevation in primarily stored heparan sulphate was observed in all brain regions assessed in MPS IIIA pups ≤9.5 weeks of age. There was a significant elevation in secondarily stored ganglioside (GM3 36:1) in ≤9.5-week-old MPS IIIA pup cerebellum, and other brain regions also exhibited accumulation of this lipid with time. The number of neural stem cells and neuronal precursor cells was essentially unchanged in MPS IIIA dog brain (c.f. unaffected) over the time course assessed, a finding corroborated by neuron cell counts. We observed early neuroinflammatory changes in young MPS IIIA pup brain, with significantly increased numbers of activated microglia recorded in all but one brain region in MPS IIIA pups ≤9.5 weeks of age (c.f. age-matched unaffected pups). In conclusion, infant-paediatric-stage MPS IIIA canine brain exhibits substantial and progressive primary and secondary substrate accumulation, coupled with early and robust microgliosis. Whilst early initiation of treatment is likely to be required to maintain optimal neurological function, the brain's neurodevelopmental potential appears largely unaffected by the disease process; further investigations confirming this are warranted.
ERIC Educational Resources Information Center
Thompson, Ross A.
2008-01-01
The past decade has seen an upsurge in public understanding of early brain development. News reports, statements by policymakers, and commercial marketing of products for infants and young children have all contributed to a widespread understanding of the explosive growth of the brain in the early years and that stimulation acts as a catalyst to…
ERIC Educational Resources Information Center
Marsh, Rachel; Gerber, Andrew J.; Peterson, Bradley S.
2008-01-01
Neuroimaging findings which identify normal brain development trajectories are presented. Results show that early brain development begins with the neural tube formation and ends with myelintation. How disturbances in brain development patterns are related to childhood psychiatric disorders is examined.
The maturation of cortical sleep rhythms and networks over early development.
Chu, C J; Leahy, J; Pathmanathan, J; Kramer, M A; Cash, S S
2014-07-01
Although neuronal activity drives all aspects of cortical development, how human brain rhythms spontaneously mature remains an active area of research. We sought to systematically evaluate the emergence of human brain rhythms and functional cortical networks over early development. We examined cortical rhythms and coupling patterns from birth through adolescence in a large cohort of healthy children (n=384) using scalp electroencephalogram (EEG) in the sleep state. We found that the emergence of brain rhythms follows a stereotyped sequence over early development. In general, higher frequencies increase in prominence with striking regional specificity throughout development. The coordination of these rhythmic activities across brain regions follows a general pattern of maturation in which broadly distributed networks of low-frequency oscillations increase in density while networks of high frequency oscillations become sparser and more highly clustered. Our results indicate that a predictable program directs the development of key rhythmic components and physiological brain networks over early development. This work expands our knowledge of normal cortical development. The stereotyped neurophysiological processes observed at the level of rhythms and networks may provide a scaffolding to support critical periods of cognitive growth. Furthermore, these conserved patterns could provide a sensitive biomarker for cortical health across development. Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
The maturation of cortical sleep rhythms and networks over early development
Chu, CJ; Leahy, J; Pathmanathan, J; Kramer, MA; Cash, SS
2014-01-01
Objective Although neuronal activity drives all aspects of cortical development, how human brain rhythms spontaneously mature remains an active area of research. We sought to systematically evaluate the emergence of human brain rhythms and functional cortical networks over early development. Methods We examined cortical rhythms and coupling patterns from birth through adolescence in a large cohort of healthy children (n=384) using scalp electroencephalogram (EEG) in the sleep state. Results We found that the emergence of brain rhythms follows a stereotyped sequence over early development. In general, higher frequencies increase in prominence with striking regional specificity throughout development. The coordination of these rhythmic activities across brain regions follows a general pattern of maturation in which broadly distributed networks of low-frequency oscillations increase in density while networks of high frequency oscillations become sparser and more highly clustered. Conclusion Our results indicate that a predictable program directs the development of key rhythmic components and physiological brain networks over early development. Significance This work expands our knowledge of normal cortical development. The stereotyped neurophysiological processes observed at the level of rhythms and networks may provide a scaffolding to support critical periods of cognitive growth. Furthermore, these conserved patterns could provide a sensitive biomarker for cortical health across development. PMID:24418219
Glenn, Dana E; Demir-Lira, Özlem Ece; Gibson, Dominic J; Congdon, Eliza L; Levine, Susan C
2018-04-01
Children with early focal unilateral brain injury show remarkable plasticity in language development. However, little is known about how early brain injury influences mathematical learning. Here, we examine early number understanding, comparing cardinal number knowledge of typically developing children (TD) and children with pre- and perinatal lesions (BI) between 42 and 50 months of age. We also examine how this knowledge relates to the number words children hear from their primary caregivers early in life. We find that children with BI, are, on average, slightly behind TD children in both cardinal number knowledge and later mathematical performance, and show slightly slower learning rates than TD children in cardinal number knowledge during the preschool years. We also find that parents' "number talk" to their toddlers predicts later mathematical ability for both TD children and children with BI. These findings suggest a relatively optimistic story in which neural plasticity is at play in children's mathematical development following early brain injury. Further, the effects of early number input suggest that intervening to enrich the number talk that children with BI hear during the preschool years could narrow the math achievement gap. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.
Jasinska, K K; Petitto, L A
2013-10-01
Is the developing bilingual brain fundamentally similar to the monolingual brain (e.g., neural resources supporting language and cognition)? Or, does early-life bilingual language experience change the brain? If so, how does age of first bilingual exposure impact neural activation for language? We compared how typically-developing bilingual and monolingual children (ages 7-10) and adults recruit brain areas during sentence processing using functional Near Infrared Spectroscopy (fNIRS) brain imaging. Bilingual participants included early-exposed (bilingual exposure from birth) and later-exposed individuals (bilingual exposure between ages 4-6). Both bilingual children and adults showed greater neural activation in left-hemisphere classic language areas, and additionally, right-hemisphere homologues (Right Superior Temporal Gyrus, Right Inferior Frontal Gyrus). However, important differences were observed between early-exposed and later-exposed bilinguals in their earliest-exposed language. Early bilingual exposure imparts fundamental changes to classic language areas instead of alterations to brain regions governing higher cognitive executive functions. However, age of first bilingual exposure does matter. Later-exposed bilinguals showed greater recruitment of the prefrontal cortex relative to early-exposed bilinguals and monolinguals. The findings provide fascinating insight into the neural resources that facilitate bilingual language use and are discussed in terms of how early-life language experiences can modify the neural systems underlying human language processing. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.
Early alterations of social brain networks in young children with autism
Kojovic, Nada; Rihs, Tonia Anahi; Jan, Reem Kais; Franchini, Martina; Plomp, Gijs; Vulliemoz, Serge; Eliez, Stephan; Michel, Christoph Martin; Schaer, Marie
2018-01-01
Social impairments are a hallmark of Autism Spectrum Disorders (ASD), but empirical evidence for early brain network alterations in response to social stimuli is scant in ASD. We recorded the gaze patterns and brain activity of toddlers with ASD and their typically developing peers while they explored dynamic social scenes. Directed functional connectivity analyses based on electrical source imaging revealed frequency specific network atypicalities in the theta and alpha frequency bands, manifesting as alterations in both the driving and the connections from key nodes of the social brain associated with autism. Analyses of brain-behavioural relationships within the ASD group suggested that compensatory mechanisms from dorsomedial frontal, inferior temporal and insular cortical regions were associated with less atypical gaze patterns and lower clinical impairment. Our results provide strong evidence that directed functional connectivity alterations of social brain networks is a core component of atypical brain development at early stages of ASD. PMID:29482718
Brain anatomical networks in early human brain development.
Fan, Yong; Shi, Feng; Smith, Jeffrey Keith; Lin, Weili; Gilmore, John H; Shen, Dinggang
2011-02-01
Recent neuroimaging studies have demonstrated that human brain networks have economic small-world topology and modular organization, enabling efficient information transfer among brain regions. However, it remains largely unknown how the small-world topology and modular organization of human brain networks emerge and develop. Using longitudinal MRI data of 28 healthy pediatric subjects, collected at their ages of 1 month, 1 year, and 2 years, we analyzed development patterns of brain anatomical networks derived from morphological correlations of brain regional volumes. The results show that the brain network of 1-month-olds has the characteristically economic small-world topology and nonrandom modular organization. The network's cost efficiency increases with the brain development to 1 year and 2 years, so does the modularity, providing supportive evidence for the hypothesis that the small-world topology and the modular organization of brain networks are established during early brain development to support rapid synchronization and information transfer with minimal rewiring cost, as well as to balance between local processing and global integration of information. Copyright © 2010. Published by Elsevier Inc.
How the Timing and Quality of Early Experiences Influence the Development of Brain Architecture
ERIC Educational Resources Information Center
Fox, Sharon E.; Levitt, Pat; Nelson, Charles A., III.
2010-01-01
Early life events can exert a powerful influence on both the pattern of brain architecture and behavioral development. In this study a conceptual framework is provided for considering how the structure of early experience gets "under the skin." The study begins with a description of the genetic framework that lays the foundation for brain…
Early Brain Development Research Review and Update
ERIC Educational Resources Information Center
Schiller, Pam
2010-01-01
Thanks to imaging technology used in neurobiology, people have access to useful and critical information regarding the development of the human brain. This information allows them to become much more effective in helping children in their early development. In fact, when people base their practices on the findings from medical science research,…
EARLY VERSUS LATE MRI IN ASPHYXIATED NEWBORNS TREATED WITH HYPOTHERMIA
Wintermark, Pia; Hansen, Anne; Soul, Janet; Labrecque, Michelle; Robertson, Richard L.; Warfield, Simon K.
2012-01-01
Objective The purposes of this feasibility study are to assess: (1) the potential utility of early brain magnetic resonance imaging (MRI) in asphyxiated newborns treated with hypothermia; (2) whether early MRI predicts later brain injury observed in these newborns after hypothermia is completed; and (3) whether early MRI indicators of brain injury in these newborns represent reversible changes. Patients and Methods All consecutive asphyxiated term newborns meeting the criteria for therapeutic hypothermia were enrolled prospectively. Each of them underwent 1–2 “early” MRI scans while receiving hypothermia, on day of life (DOL) 1 and DOL 2–3, and also 1–2 “late” MRI scans on DOL 8–13 and at 1 month of age. Results Thirty-seven MRI scans were obtained in twelve asphyxiated neonates treated with induced hypothermia. Four newborns did develop MRI evidence of brain injury, already visible on early MRI scans. The remaining eight newborns did not develop significant MRI evidence of brain injury on any of the MRI scans. In addition, two patients displayed unexpected findings on early MRIs, leading to early termination of hypothermia treatment. Conclusions MRI scans obtained on DOL 2–3 during hypothermia seem to predict later brain injuries in asphyxiated newborns in this feasibility study. Brain injuries identified during this early time appear to represent irreversible changes. Early MRI scans might also be useful to demonstrate unexpected findings not related to hypoxic-ischemic encephalopathy, which could potentially be exacerbated by induced hypothermia. Additional studies with larger numbers of patients will be useful to more definitively confirm these results. PMID:20688865
Kight, Katherine E; McCarthy, Margaret M
2014-12-01
Sexual differentiation of the developing brain organizes the neural architecture differently between males and females, and the main influence on this process is exposure to gonadal steroids during sensitive periods of prenatal and early postnatal development. Many molecular and cellular processes are influenced by steroid hormones in the developing brain, including gene expression, cell birth and death, neurite outgrowth and synaptogenesis, and synaptic activity. Perturbations in these processes can alter neuronal excitability and circuit activity, leading to increased seizure susceptibility and the promotion of pathological processes that constitute epileptogenesis. In this review, we will provide a general overview of sex differences in the early developing brain that may be relevant for altered seizure susceptibility in early life, focusing on limbic areas of the brain. Sex differences that have the potential to alter the progress of epileptogenesis are evident at molecular and cellular levels in the developing brain, and include differences in neuronal excitability, response to environmental insult, and epigenetic control of gene expression. Knowing how these processes differ between the sexes can help us understand fundamental mechanisms underlying gender differences in seizure susceptibility and epileptogenesis. Copyright © 2014 Elsevier Inc. All rights reserved.
Steroid hormones, stress and the adolescent brain: a comparative perspective.
Brown, G R; Spencer, K A
2013-09-26
Steroid hormones, including those produced by the gonads and the adrenal glands, are known to influence brain development during sensitive periods of life. Until recently, most brain organisation was assumed to take place during early stages of development, with relatively little neurogenesis or brain re-organisation during later stages. However, an increasing body of research has shown that the developing brain is also sensitive to steroid hormone exposure during adolescence (broadly defined as the period from nutritional independence to sexual maturity). In this review, we examine how steroid hormones that are produced by the gonads and adrenal glands vary across the lifespan in a range of mammalian and bird species, and we summarise the evidence that steroid hormone exposure influences behavioural and brain development during early stages of life and during adolescence in these two taxonomic groups. Taking a cross-species, comparative perspective reveals that the effects of early exposure to steroid hormones depend upon the stage of development at birth or hatching, as measured along the altricial-precocial dimension. We then review the evidence that exposure to stress during adolescence impacts upon the developing neuroendocrine systems, the brain and behaviour. Current research suggests that the effects of adolescent stress vary depending upon the sex of the individual and type of stressor, and the effects of stress could involve several neural systems, including the serotonergic and dopaminergic systems. Experience of stressors during adolescence could also influence brain development via the close interactions between the stress hormone and gonadal hormone axes. While sensitivity of the brain to steroid hormones during early life and adolescence potentially leaves the developing organism vulnerable to external adversities, developmental plasticity also provides an opportunity for the developing organism to respond to current circumstances and for behavioural responses to influence the future life history of the individual. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.
Delineation of early brain development from fetuses to infants with diffusion MRI and beyond.
Ouyang, Minhui; Dubois, Jessica; Yu, Qinlin; Mukherjee, Pratik; Huang, Hao
2018-04-12
Dynamic macrostructural and microstructural changes take place from the mid-fetal stage to 2 years after birth. Delineating structural changes of the brain during early development provides new insights into the complicated processes of both typical development and the pathological mechanisms underlying various psychiatric and neurological disorders including autism, attention deficit hyperactivity disorder and schizophrenia. Decades of histological studies have identified strong spatial and functional maturation gradients in human brain gray and white matter. The recent improvements in magnetic resonance imaging (MRI) techniques, especially diffusion MRI (dMRI), relaxometry imaging, and magnetization transfer imaging (MTI) have provided unprecedented opportunities to non-invasively quantify and map the early developmental changes at whole brain and regional levels. Here, we review the recent advances in understanding early brain structural development during the second half of gestation and the first two postnatal years using modern MR techniques. Specifically, we review studies that delineate the emergence and microstructural maturation of white matter tracts, as well as dynamic mapping of inhomogeneous cortical microstructural organization unique to fetuses and infants. These imaging studies converge into maturational curves of MRI measurements that are distinctive across different white matter tracts and cortical regions. Furthermore, contemporary models offering biophysical interpretations of the dMRI-derived measurements are illustrated to infer the underlying microstructural changes. Collectively, this review summarizes findings that contribute to charting spatiotemporally heterogeneous gray and white matter structural development, offering MRI-based biomarkers of typical brain development and setting the stage for understanding aberrant brain development in neurodevelopmental disorders. Copyright © 2018 Elsevier Inc. All rights reserved.
Early brain development in infants at high risk for autism spectrum disorder
Hazlett, Heather Cody; Gu, Hongbin; Munsell, Brent C.; Kim, Sun Hyung; Styner, Martin; Wolff, Jason J.; Elison, Jed T.; Swanson, Meghan R.; Zhu, Hongtu; Botteron, Kelly N.; Collins, D. Louis; Constantino, John N.; Dager, Stephen R.; Estes, Annette M.; Evans, Alan C.; Fonov, Vladimir S.; Gerig, Guido; Kostopoulos, Penelope; McKinstry, Robert C.; Pandey, Juhi; Paterson, Sarah; Pruett, John R.; Schultz, Robert T.; Shaw, Dennis W.; Zwaigenbaum, Lonnie; Piven, Joseph
2017-01-01
Summary Brain enlargement has been observed in children with Autism Spectrum Disorder (ASD), but the timing of this phenomenon and its relationship to the appearance of behavioral symptoms is unknown. Retrospective head circumference and longitudinal brain volume studies of 2 year olds followed up at age 4 years, have provided evidence that increased brain volume may emerge early in development.1, 2 Studies of infants at high familial risk for autism can provide insight into the early development of autism and have found that characteristic social deficits in ASD emerge during the latter part of the first and in the second year of life3,4. These observations suggest that prospective brain imaging studies of infants at high familial risk for ASD might identify early post-natal changes in brain volume occurring before the emergence of an ASD diagnosis. In this prospective neuroimaging study of 106 infants at high familial risk of ASD and 42 low-risk infants, we show that cortical surface area hyper-expansion between 6-12 months of age precedes brain volume overgrowth observed between 12-24 months in the 15 high-risk infants diagnosed with autism at 24 months. Brain volume overgrowth was linked to the emergence and severity of autistic social deficits. A deep learning algorithm primarily using surface area information from brain MRI at 6 and 12 months of age predicted the diagnosis of autism in individual high-risk children at 24 months (with a positive predictive value of 81%, sensitivity of 88%). These findings demonstrate that early brain changes unfold during the period in which autistic behaviors are first emerging. PMID:28202961
Early brain development in infants at high risk for autism spectrum disorder.
Hazlett, Heather Cody; Gu, Hongbin; Munsell, Brent C; Kim, Sun Hyung; Styner, Martin; Wolff, Jason J; Elison, Jed T; Swanson, Meghan R; Zhu, Hongtu; Botteron, Kelly N; Collins, D Louis; Constantino, John N; Dager, Stephen R; Estes, Annette M; Evans, Alan C; Fonov, Vladimir S; Gerig, Guido; Kostopoulos, Penelope; McKinstry, Robert C; Pandey, Juhi; Paterson, Sarah; Pruett, John R; Schultz, Robert T; Shaw, Dennis W; Zwaigenbaum, Lonnie; Piven, Joseph
2017-02-15
Brain enlargement has been observed in children with autism spectrum disorder (ASD), but the timing of this phenomenon, and the relationship between ASD and the appearance of behavioural symptoms, are unknown. Retrospective head circumference and longitudinal brain volume studies of two-year olds followed up at four years of age have provided evidence that increased brain volume may emerge early in development. Studies of infants at high familial risk of autism can provide insight into the early development of autism and have shown that characteristic social deficits in ASD emerge during the latter part of the first and in the second year of life. These observations suggest that prospective brain-imaging studies of infants at high familial risk of ASD might identify early postnatal changes in brain volume that occur before an ASD diagnosis. In this prospective neuroimaging study of 106 infants at high familial risk of ASD and 42 low-risk infants, we show that hyperexpansion of the cortical surface area between 6 and 12 months of age precedes brain volume overgrowth observed between 12 and 24 months in 15 high-risk infants who were diagnosed with autism at 24 months. Brain volume overgrowth was linked to the emergence and severity of autistic social deficits. A deep-learning algorithm that primarily uses surface area information from magnetic resonance imaging of the brain of 6-12-month-old individuals predicted the diagnosis of autism in individual high-risk children at 24 months (with a positive predictive value of 81% and a sensitivity of 88%). These findings demonstrate that early brain changes occur during the period in which autistic behaviours are first emerging.
NASA Astrophysics Data System (ADS)
Fini, Jean-Baptiste; Mughal, Bilal B.; Le Mével, Sébastien; Leemans, Michelle; Lettmann, Mélodie; Spirhanzlova, Petra; Affaticati, Pierre; Jenett, Arnim; Demeneix, Barbara A.
2017-03-01
Thyroid hormones are essential for normal brain development in vertebrates. In humans, abnormal maternal thyroid hormone levels during early pregnancy are associated with decreased offspring IQ and modified brain structure. As numerous environmental chemicals disrupt thyroid hormone signalling, we questioned whether exposure to ubiquitous chemicals affects thyroid hormone responses during early neurogenesis. We established a mixture of 15 common chemicals at concentrations reported in human amniotic fluid. An in vivo larval reporter (GFP) assay served to determine integrated thyroid hormone transcriptional responses. Dose-dependent effects of short-term (72 h) exposure to single chemicals and the mixture were found. qPCR on dissected brains showed significant changes in thyroid hormone-related genes including receptors, deiodinases and neural differentiation markers. Further, exposure to mixture also modified neural proliferation as well as neuron and oligodendrocyte size. Finally, exposed tadpoles showed behavioural responses with dose-dependent reductions in mobility. In conclusion, exposure to a mixture of ubiquitous chemicals at concentrations found in human amniotic fluid affect thyroid hormone-dependent transcription, gene expression, brain development and behaviour in early embryogenesis. As thyroid hormone signalling is strongly conserved across vertebrates the results suggest that ubiquitous chemical mixtures could be exerting adverse effects on foetal human brain development.
Recent Brain Research on Young Children.
ERIC Educational Resources Information Center
Flohr, John W.
1999-01-01
Provides information about current brain research. Explains that some of the basic tenets that have guided research are outlined in R. Shore's "Rethinking the Brain: New Insights into Early Development." Offers five hypotheses: (1) nature/nurture; (2) effects of nurture; (3) optimal music learning; (4) minimal disadvantages; and (5) early music…
The maternal brain and its plasticity in humans
Kim, Pilyoung; Strathearn, Lane; Swain, James E.
2015-01-01
Early mother-infant relationships play important roles in infants’ optimal development. New mothers undergo neurobiological changes that support developing mother-infant relationships regardless of great individual differences in those relationships. In this article, we review the neural plasticity in human mothers’ brains based on functional magnetic resonance imaging (fMRI) studies. First, we review the neural circuits that are involved in establishing and maintaining mother-infant relationships. Second, we discuss early postpartum factors (e.g., birth and feeding methods, hormones, and parental sensitivity) that are associated with individual differences in maternal brain neuroplasticity. Third, we discuss abnormal changes in the maternal brain related to psychopathology (i.e., postpartum depression, posttraumatic stress disorder, substance abuse) and potential brain remodeling associated with interventions. Last, we highlight potentially important future research directions to better understand normative changes in the maternal brain and risks for abnormal changes that may disrupt early mother-infant relationships. PMID:26268151
Genetic and Diagnostic Biomarker Development in ASD Toddlers Using Resting State Functional MRI
2015-09-01
for public release; distribution unlimited Autism spectrum disorder (ASD); biomarker; early brain development; intrinsic functional brain networks...three large neuroimaging/neurobehavioral datasets to identify brain-imaging based biomarkers for Autism Spectrum Disorders (ASD). At Yale, we focus...neurobehavioral!datasets!in!order!to!identify! brainFimaging!based!biomarkers!for! Autism ! Spectrum ! Disorders !(ASD),!including!1)!BrainMap,! developed!and
The evolution of modern human brain shape
Neubauer, Simon; Hublin, Jean-Jacques; Gunz, Philipp
2018-01-01
Modern humans have large and globular brains that distinguish them from their extinct Homo relatives. The characteristic globularity develops during a prenatal and early postnatal period of rapid brain growth critical for neural wiring and cognitive development. However, it remains unknown when and how brain globularity evolved and how it relates to evolutionary brain size increase. On the basis of computed tomographic scans and geometric morphometric analyses, we analyzed endocranial casts of Homo sapiens fossils (N = 20) from different time periods. Our data show that, 300,000 years ago, brain size in early H. sapiens already fell within the range of present-day humans. Brain shape, however, evolved gradually within the H. sapiens lineage, reaching present-day human variation between about 100,000 and 35,000 years ago. This process started only after other key features of craniofacial morphology appeared modern and paralleled the emergence of behavioral modernity as seen from the archeological record. Our findings are consistent with important genetic changes affecting early brain development within the H. sapiens lineage since the origin of the species and before the transition to the Later Stone Age and the Upper Paleolithic that mark full behavioral modernity. PMID:29376123
The evolution of modern human brain shape.
Neubauer, Simon; Hublin, Jean-Jacques; Gunz, Philipp
2018-01-01
Modern humans have large and globular brains that distinguish them from their extinct Homo relatives. The characteristic globularity develops during a prenatal and early postnatal period of rapid brain growth critical for neural wiring and cognitive development. However, it remains unknown when and how brain globularity evolved and how it relates to evolutionary brain size increase. On the basis of computed tomographic scans and geometric morphometric analyses, we analyzed endocranial casts of Homo sapiens fossils ( N = 20) from different time periods. Our data show that, 300,000 years ago, brain size in early H. sapiens already fell within the range of present-day humans. Brain shape, however, evolved gradually within the H. sapiens lineage, reaching present-day human variation between about 100,000 and 35,000 years ago. This process started only after other key features of craniofacial morphology appeared modern and paralleled the emergence of behavioral modernity as seen from the archeological record. Our findings are consistent with important genetic changes affecting early brain development within the H. sapiens lineage since the origin of the species and before the transition to the Later Stone Age and the Upper Paleolithic that mark full behavioral modernity.
Normal variation in early parental sensitivity predicts child structural brain development.
Kok, Rianne; Thijssen, Sandra; Bakermans-Kranenburg, Marian J; Jaddoe, Vincent W V; Verhulst, Frank C; White, Tonya; van IJzendoorn, Marinus H; Tiemeier, Henning
2015-10-01
Early caregiving can have an impact on brain structure and function in children. The influence of extreme caregiving experiences has been demonstrated, but studies on the influence of normal variation in parenting quality are scarce. Moreover, no studies to date have included the role of both maternal and paternal sensitivity in child brain maturation. This study examined the prospective relation between mothers' and fathers' sensitive caregiving in early childhood and brain structure later in childhood. Participants were enrolled in a population-based prenatal cohort. For 191 families, maternal and paternal sensitivity was repeatedly observed when the child was between 1 year and 4 years of age. Head circumference was assessed at 6 weeks, and brain structure was assessed using magnetic resonance imaging (MRI) measurements at 8 years of age. Higher levels of parental sensitivity in early childhood were associated with larger total brain volume (adjusted β = 0.15, p = .01) and gray matter volume (adjusted β = 0.16, p = .01) at 8 years, controlling for infant head size. Higher levels of maternal sensitivity in early childhood were associated with a larger gray matter volume (adjusted β = 0.13, p = .04) at 8 years, independent of infant head circumference. Associations with maternal versus paternal sensitivity were not significantly different. Normal variation in caregiving quality is related to markers of more optimal brain development in children. The results illustrate the important role of both mothers and fathers in child brain development. Copyright © 2015 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.
Educating the Human Brain. Human Brain Development Series
ERIC Educational Resources Information Center
Posner, Michael I.; Rothbart, Mary K.
2006-01-01
"Educating the Human Brain" is the product of a quarter century of research. This book provides an empirical account of the early development of attention and self regulation in infants and young children. It examines the brain areas involved in regulatory networks, their connectivity, and how their development is influenced by genes and…
A Survey of English Sixth Formers' Knowledge of Early Brain Development.
Nolan, Mary
2017-10-01
Objectives To ascertain the knowledge of young people aged 16 to 19 of early brain development and their attitudes towards the care of babies and preschool children. Design Cross-sectional, school- and college-based survey including all sixth form students present on the days of data collection. The survey instrument comprised forced-choice questions in four sections: Demographics, Perceptions and Understanding of Early Childhood Development, Parental Behaviors to Support Early Brain development, and Resource Needs and Usage. Setting Two sixth form schools and one sixth form college in three towns of varying affluence in the West Midlands of the United Kingdom. Method The survey was mounted online and completed by 905 students who returned it directly to the researcher. Results Most students knew that tobacco, alcohol, and drugs are hazardous in pregnancy, and many recognized the impact of maternal stress on fetal brain development. Many believed that babies can be "spoiled" and did not appreciate the importance of reading to babies and of the relationship between play and early brain development. A significant minority thought that physical activity and a healthy diet have little impact on young children's development. Respondents said they would turn firstly to their parents for advice on baby care rather than professionals. Conclusion Young people need educating about parenting activities that support the all-round healthy development of infants. The importance of a healthy diet, physical activity, reading, and play should be included in sixth form curricula and antenatal classes. Consideration should be given to educating grandparents because of their influence on new parents.
Reduced Cortical Activity Impairs Development and Plasticity after Neonatal Hypoxia Ischemia
Ranasinghe, Sumudu; Or, Grace; Wang, Eric Y.; Ievins, Aiva; McLean, Merritt A.; Niell, Cristopher M.; Chau, Vann; Wong, Peter K. H.; Glass, Hannah C.; Sullivan, Joseph
2015-01-01
Survivors of preterm birth are at high risk of pervasive cognitive and learning impairments, suggesting disrupted early brain development. The limits of viability for preterm birth encompass the third trimester of pregnancy, a “precritical period” of activity-dependent development characterized by the onset of spontaneous and evoked patterned electrical activity that drives neuronal maturation and formation of cortical circuits. Reduced background activity on electroencephalogram (EEG) is a sensitive marker of brain injury in human preterm infants that predicts poor neurodevelopmental outcome. We studied a rodent model of very early hypoxic–ischemic brain injury to investigate effects of injury on both general background and specific patterns of cortical activity measured with EEG. EEG background activity is depressed transiently after moderate hypoxia–ischemia with associated loss of spindle bursts. Depressed activity, in turn, is associated with delayed expression of glutamate receptor subunits and transporters. Cortical pyramidal neurons show reduced dendrite development and spine formation. Complementing previous observations in this model of impaired visual cortical plasticity, we find reduced somatosensory whisker barrel plasticity. Finally, EEG recordings from human premature newborns with brain injury demonstrate similar depressed background activity and loss of bursts in the spindle frequency band. Together, these findings suggest that abnormal development after early brain injury may result in part from disruption of specific forms of brain activity necessary for activity-dependent circuit development. SIGNIFICANCE STATEMENT Preterm birth and term birth asphyxia result in brain injury from inadequate oxygen delivery and constitute a major and growing worldwide health problem. Poor outcomes are noted in a majority of very premature (<25 weeks gestation) newborns, resulting in death or life-long morbidity with motor, sensory, learning, behavioral, and language disabilities that limit academic achievement and well-being. Limited progress has been made to develop therapies that improve neurologic outcomes. The overall objective of this study is to understand the effect of early brain injury on activity-dependent brain development and cortical plasticity to develop new treatments that will optimize repair and recovery after brain injury. PMID:26311776
Kotrschal, Alexander; Trombley, Susanne; Rogell, Björn; Brannström, Ioana; Foconi, Eric; Schmitz, Monika; Kolm, Niclas
It has been suggested that mating behaviours require high levels of cognitive ability. However, since investment into mating and the brain both are costly features, their relationship is likely characterized by energetic trade-offs. Empirical data on the subject remains equivocal. We investigated if early sexual maturation was associated with brain development in Atlantic salmon ( Salmo salar ), in which males can either stay in the river and sexually mature at a small size (sneaker males) or migrate to the sea and delay sexual maturation until they have grown much larger (anadromous males). Specifically, we tested how sexual maturation may induce plastic changes in brain development by rearing juveniles on either natural or ad libitum feeding levels. After their first season we compared brain size and brain region volumes across both types of male mating tactics and females. Body growth increased greatly across both male mating tactics and females during ad libitum feeding as compared to natural feeding levels. However, despite similar relative increases in body size, early maturing sneaker males maintained larger relative brain size during ad libitum feeding levels as compared to anadromous males and females. We also detected several differences in the relative size of separate brain regions across feeding treatments, sexes and mating strategies. For instance, the relative size of the cognitive centre of the brain, the telencephalon, was largest in sneaker males. Our data support that a large relative brain size is maintained in individuals that start reproduction early also during fast body growth. We propose that the cognitive demands during complex mating behaviours maintain a high level of investment into brain development in reproducing individuals.
Approaches to Learning: Supporting Brain Development for School Success
ERIC Educational Resources Information Center
Petersen, Sandra
2012-01-01
Prenatally and in infants and toddlers, the brain is being constructed as a foundation for all later learning. Positive early experiences contribute to the formation of a brain that is capable, early in infancy, of utilizing and strengthening the basic processes of learning. Throughout a lifetime, a person will repeatedly use these approaches to…
O'Connor, Cliodhna; Joffe, Helene
2013-11-01
The public profile of neurodevelopmental research has expanded in recent years. This paper applies social representations theory to explore how early brain development was represented in the UK print media in the first decade of the 21st century. A thematic analysis was performed on 505 newspaper articles published between 2000 and 2010 that discussed early brain development. Media coverage centred around concern with 'protecting' the prenatal brain (identifying threats to foetal neurodevelopment), 'feeding' the infant brain (indicating the patterns of nutrition that enhance brain development) and 'loving' the young child's brain (elucidating the developmental significance of emotionally nurturing family environments). The media focused almost exclusively on the role of parental action in promoting optimal neurodevelopment, rarely acknowledging wider structural, cultural or political means of supporting child development. The significance of parental care was intensified by deterministic interpretations of critical periods, which implied that inappropriate parental input would produce profound and enduring neurobiological impairments. Neurodevelopmental research was also used to promulgate normative judgements concerning the acceptability of certain gender roles and family contexts. The paper argues that media representations of neurodevelopment stress parental responsibility for shaping a child's future while relegating the contributions of genetic or wider societal factors, and examines the consequences of these representations for society and family life. Copyright © 2012 Elsevier Ltd. All rights reserved.
Rao, Hengyi; Betancourt, Laura; Giannetta, Joan M; Brodsky, Nancy L; Korczykowski, Marc; Avants, Brian B; Gee, James C; Wang, Jiongjiong; Hurt, Hallam; Detre, John A; Farah, Martha J
2010-01-01
The effects of early life experience on later brain structure and function have been studied extensively in animals, yet the relationship between childhood experience and normal brain development in humans remains largely unknown. Using a unique longitudinal data set including ecologically valid in-home measures of early experience during childhood (at age 4 and 8 years) and high-resolution structural brain imaging during adolescence (mean age 14 years), we examined the effects on later brain morphology of two dimensions of early experience: parental nurturance and environmental stimulation. Parental nurturance at age 4 predicts the volume of the left hippocampus in adolescence, with better nurturance associated with smaller hippocampal volume. In contrast, environmental stimulation did not correlate with hippocampal volume. Moreover, the association between hippocampal volume and parental nurturance disappears at age 8, supporting the existence of a sensitive developmental period for brain maturation. These findings indicate that variation in normal childhood experience is associated with differences in brain morphology, and hippocampal volume is specifically associated with early parental nurturance. Our results provide neuroimaging evidence supporting the important role of warm parental care during early childhood for brain maturation.
ERIC Educational Resources Information Center
Wulfeck, Beverly; Bates, Elizabeth; Krupa-Kwiatkowski, Magda; Saltzman, Danna
2004-01-01
Grammaticality judgments and processing times associated with violation detection were examined in typically developing children, children with focal brain lesions (FL) acquired early in life, and children with specific language impairment (SLI). Grammatical sensitivity in the FL group, while below typically developing children, was above levels…
Primary Cortical Folding in the Human Newborn: An Early Marker of Later Functional Development
ERIC Educational Resources Information Center
Dubois, J.; Benders, M.; Borradori-Tolsa, C.; Cachia, A.; Lazeyras, F.; Leuchter, R. Ha-Vinh; Sizonenko, S. V.; Warfield, S. K.; Mangin, J. F.; Huppi, P. S.
2008-01-01
In the human brain, the morphology of cortical gyri and sulci is complex and variable among individuals, and it may reflect pathological functioning with specific abnormalities observed in certain developmental and neuropsychiatric disorders. Since cortical folding occurs early during brain development, these structural abnormalities might be…
Start Smart! Building Brain Power in the Early Years.
ERIC Educational Resources Information Center
Schiller, Pam
Noting current brain development research, this book offers simple, straightforward ways to boost children's brain power with active exploration, repetition, sensory exploration, laughter, and more. The chapters describe how and why the brain develops and explain how parents can give their children the best foundation for future learning.…
ERIC Educational Resources Information Center
Demir, Özlem Ece; Rowe, Meredith L.; Heller, Gabriella; Goldin-Meadow, Susan; Levine, Susan C.
2015-01-01
This study examines the role of a particular kind of linguistic input--talk about the past and future, pretend, and explanations, that is, talk that is decontextualized--in the development of vocabulary, syntax, and narrative skill in typically developing (TD) children and children with pre- or perinatal brain injury (BI). Decontextualized talk…
ERIC Educational Resources Information Center
Pavlova, Marina A.; Krageloh-Mann, Ingeborg
2013-01-01
Brain lesions to the white matter in peritrigonal regions, periventricular leukomalacia, in children who were born prematurely represent an important model for studying limitations on brain development. The lesional pattern is of early origin and bilateral, that constrains the compensatory potential of the brain. We suggest that (i) topography and…
Parker, Matthew O; Evans, Alexandra M-D; Brock, Alistair J; Combe, Fraser J; Teh, Muy-Teck; Brennan, Caroline H
2016-01-01
Exposure to alcohol during early central nervous system development has been shown variously to affect aspects of physiological and behavioural development. In extreme cases, this can extend to craniofacial defects, severe developmental delay and mental retardation. At more moderate levels, subtle differences in brain morphology and behaviour have been observed. One clear effect of developmental alcohol exposure is an increase in the propensity to develop alcoholism and other addictions. The mechanisms by which this occurs, however, are not currently understood. In this study, we tested the hypothesis that adult zebrafish chronically exposed to moderate levels of ethanol during early brain ontogenesis would show an increase in conditioned place preference for alcohol and an increased propensity towards habit formation, a key component of drug addiction in humans. We found support for both of these hypotheses and found that the exposed fish had changes in mRNA expression patterns for dopamine receptor, nicotinic acetylcholine receptor and μ-opioid receptor encoding genes. Collectively, these data show an explicit link between the increased proclivity for addiction and addiction-related behaviour following exposure to ethanol during early brain development and alterations in the neural circuits underlying habit learning. © 2014 Society for the Study of Addiction.
Tuning the developing brain to social signals of emotions
Leppänen, Jukka M.; Nelson, Charles A.
2010-01-01
PREFACE Humans in diverse cultures develop a similar capacity to recognize the emotional signals of different facial expressions. This capacity is mediated by a brain network that involves emotion-related brain circuits and higher-level visual representation areas. Recent studies suggest that the key components of this network begin to emerge early in life. The studies also suggest that initial biases in emotion-related brain circuits and the early coupling of these circuits and cortical perceptual areas provides a foundation for a rapid acquisition of representations of those facial features that denote specific emotions. PMID:19050711
Socioeconomic Status and Functional Brain Development--Associations in Early Infancy
ERIC Educational Resources Information Center
Tomalski, Przemyslaw; Moore, Derek G.; Ribeiro, Helena; Axelsson, Emma L.; Murphy, Elizabeth; Karmiloff-Smith, Annette; Johnson, Mark H.; Kushnerenko, Elena
2013-01-01
Socioeconomic status (SES) impacts on both structural and functional brain development in childhood, but how early its effects can be demonstrated is unknown. In this study we measured resting baseline EEG activity in the gamma frequency range in awake 6-9-month-olds from areas of East London with high socioeconomic deprivation. Between-subject…
Bogart, Stephanie L.; Bennett, Allyson J.; Schapiro, Steven J.; Reamer, Lisa A.; Hopkins, William D.
2014-01-01
Consequences of rearing history in chimpanzees (Pan troglodytes) have been explored in relation to behavioral abnormalities and cognition, however, little is known about the effects of rearing conditions on anatomical brain development. Human studies have revealed that experiences of maltreatment and neglect during infancy and childhood can have detrimental effects on brain development and cognition. In this study, we evaluated the effects of early rearing experience on brain morphology in 92 captive chimpanzees (ages 11-43) who were either reared by their mothers (n = 46) or in a nursery (n = 46) with age-group peers. Magnetic resonance brain images were analyzed with a processing program (BrainVISA) that extracts cortical sulci. We obtained various measurements from 11 sulci located throughout the brain, as well as whole brain gyrification and white and grey matter volumes. We found that mother-reared chimpanzees have greater global white-to-grey matter volume, more cortical folding and thinner grey matter within the cortical folds than nursery-reared animals. The findings reported here are the first to demonstrate that differences in early rearing conditions have significant consequences on brain morphology in chimpanzees and suggests potential differences in the development of white matter expansion and myelination. PMID:24206013
Bogart, Stephanie L; Bennett, Allyson J; Schapiro, Steven J; Reamer, Lisa A; Hopkins, William D
2014-03-01
Consequences of rearing history in chimpanzees (Pan troglodytes) have been explored in relation to behavioral abnormalities and cognition; however, little is known about the effects of rearing conditions on anatomical brain development. Human studies have revealed that experiences of maltreatment and neglect during infancy and childhood can have detrimental effects on brain development and cognition. In this study, we evaluated the effects of early rearing experience on brain morphology in 92 captive chimpanzees (ages 11-43) who were either reared by their mothers (n = 46) or in a nursery (n = 46) with age-group peers. Magnetic resonance brain images were analyzed with a processing program (BrainVISA) that extracts cortical sulci. We obtained various measurements from 11 sulci located throughout the brain, as well as whole brain gyrification and white and grey matter volumes. We found that mother-reared chimpanzees have greater global white-to-grey matter volume, more cortical folding and thinner grey matter within the cortical folds than nursery-reared animals. The findings reported here are the first to demonstrate that differences in early rearing conditions have significant consequences on brain morphology in chimpanzees and suggests potential differences in the development of white matter expansion and myelination. © 2013 John Wiley & Sons Ltd.
Narrative discourse in children with early focal brain injury.
Reilly, J S; Bates, E A; Marchman, V A
1998-02-15
Children with early brain damage, unlike adult stroke victims, often go on to develop nearly normal language. However, the route and extent of their linguistic development are still unclear, as is the relationship between lesion site and patterns of delay and recovery. Here we address these questions by examining narratives from children with early brain damage. Thirty children (ages 3:7-10:10) with pre- or perinatal unilateral focal brain damage and their matched controls participated in a storytelling task. Analyses focused on linguistic proficiency and narrative competence. Overall, children with brain damage scored significantly lower than their age-matched controls on both linguistic (morphological and syntactic) indices and those targeting broader narrative qualities. Rather than indicating that children with brain damage fully catch up, these data suggest that deficits in linguistic abilities reassert themselves as children face new linguistic challenges. Interestingly, after age 5, site of lesion does not appear to be a significant factor and the delays we have witnessed do not map onto the lesion profiles observed in adults with analogous brain injuries.
Brandstätter, R; Kotrschal, K
1989-01-01
The present study deals with aspects of the brain development in the roach, Rutilus rutilus, a common mid-European cyprinid fish. The morphogenesis of selected brain areas from hatching to early juveniles was examined on serial paraffin cross-sections. From early juveniles to large adults, brain growth was quantitatively analyzed by computer-aided planimetry. The hatchlings of roach show a cytologically distinct optic tectum, but a poorly differentiated brainstem, reflecting the predominance of the optic sense during the larval planktivorous period. The differentiation and outgrowth of chemosensory brainstem centers is related to the onset and development of benthivorous feeding in juveniles. The optic tectum decreases in size relative to the total brain volume from juveniles through adults. The corpus cerebelli increases in relative size, whereas chemosensory and acousticolateral centers grow isometrically with the brain as a whole.
Development of an assisting detection system for early infarct diagnosis
DOE Office of Scientific and Technical Information (OSTI.GOV)
Sim, K. S.; Nia, M. E.; Ee, C. S.
2015-04-24
In this paper, a detection assisting system for early infarct detection is developed. This new developed method is used to assist the medical practitioners to diagnose infarct from computed tomography images of brain. Using this assisting system, the infarct could be diagnosed at earlier stages. The non-contrast computed tomography (NCCT) brain images are the data set used for this system. Detection module extracts the pixel data from NCCT brain images, and produces the colourized version of images. The proposed method showed great potential in detecting infarct, and helps medical practitioners to make earlier and better diagnoses.
Cholinergic Mechanisms, Early Brain Development, and Risk for Schizophrenia
Ross, Randal G; Stevens, Karen E; Proctor, William R; Leonard, Sherry; Kisley, Michael A; Hunter, Sharon K; Freedman, Robert; Adams, Catherine E
2009-01-01
Neuropsychiatric diseases are complex illnesses where the onset of diagnostic symptomology is often the end result of a decades-long process of aberrant brain development. The identification of novel treatment strategies aimed at normalizing early brain development and preventing mental illness should be a major therapeutic goal; however, there are few models for how this goal might be achieved. This report uses the attentional deficits of schizophrenia as an example and reviews data from genetic, anatomical, physiological, and pharmacologic studies to hypothesize a developmental model with translational primary prevention implications. Specifically, the model suggests that an early interaction between α7 nicotinic receptor density and choline availability may contribute to the development of schizophrenia-associated attentional deficits. Translational implications, including perinatal dietary choline supplementation, are discussed. It is hoped that presentation of this model will stimulate other efforts to develop empirically-driven primary prevention strategies. PMID:19925602
125 Brain Games for Babies: Simple Games To Promote Early Brain Development.
ERIC Educational Resources Information Center
Silberg, Jackie
Scientists believe that the stimulation that infants and young children receive determines which synapses form in the brain. This book presents 125 games for infants from birth to 12 months and is designed to nurture brain development. The book is organized chronologically in 3-month increments. Each game description includes information from…
The motivation for very early intervention for infants at high risk for autism spectrum disorders.
Webb, Sara Jane; Jones, Emily J H; Kelly, Jean; Dawson, Geraldine
2014-02-01
The first Autism Research Matrix (IACC, 2003) listed the identification of behavioural and biological markers of risk for autism as a top priority. This emphasis was based on the hypothesis that intervention with infants at-risk, at an early age when the brain is developing and before core autism symptoms have emerged, could significantly alter the developmental trajectory of children at risk for the disorder and impact long-range outcome. Research has provided support for specific models of early autism intervention (e.g., Early Start Denver Model) for improving outcomes in young children with autism, based on both behavioural and brain activity measures. Although great strides have been made in ability to identify risk markers for autism in younger infant/toddler samples, how and when to intervene during the prodromal state remains a critical question. Emerging evidence suggests that abnormal brain circuitry in autism precedes altered social behaviours; thus, an intervention designed to promote early social engagement and reciprocity potentially could steer brain development back toward the normal trajectory and remit or reduce the expression of symptoms.
Detection and mapping of delays in early cortical folding derived from in utero MRI
NASA Astrophysics Data System (ADS)
Habas, Piotr A.; Rajagopalan, Vidya; Scott, Julia A.; Kim, Kio; Roosta, Ahmad; Rousseau, Francois; Barkovich, A. James; Glenn, Orit A.; Studholme, Colin
2011-03-01
Understanding human brain development in utero and detecting cortical abnormalities related to specific clinical conditions is an important area of research. In this paper, we describe and evaluate methodology for detection and mapping of delays in early cortical folding from population-based studies of fetal brain anatomies imaged in utero. We use a general linear modeling framework to describe spatiotemporal changes in curvature of the developing brain and explore the ability to detect and localize delays in cortical folding in the presence of uncertainty in estimation of the fetal age. We apply permutation testing to examine which regions of the brain surface provide the most statistical power to detect a given folding delay at a given developmental stage. The presented methodology is evaluated using MR scans of fetuses with normal brain development and gestational ages ranging from 20.57 to 27.86 weeks. This period is critical in early cortical folding and the formation of the primary and secondary sulci. Finally, we demonstrate a clinical application of the framework for detection and localization of folding delays in fetuses with isolated mild ventriculomegaly.
Melendez-Ferro, Miguel; Perez-Costas, Emma; Glover, Matthew E.; Jackson, Nateka L.; Stringfellow, Sara A.; Pugh, Phyllis C.; Fant, Andrew D.; Clinton, Sarah M.
2016-01-01
Individual differences in human temperament can increase risk for psychiatric disorders like depression and anxiety. Our laboratory utilized a rat model of temperamental differences to assess neurodevelopmental factors underlying emotional behavior differences. Rats selectively bred for low novelty exploration (Low Responders, LR) display high levels of anxiety- and depression-like behavior compared to High Novelty Responder (HR) rats. Using transcriptome profiling, the present study uncovered vast gene expression differences in the early postnatal HR versus LR limbic brain, including changes in genes involved in cellular metabolism. These data led us to hypothesize that rats prone to high (versus low) anxiety/depression-like behavior exhibit distinct patterns of brain metabolism during the first weeks of life, which may reflect disparate patterns of synaptogenesis and brain circuit development. Thus, in a second experiment we examined activity of Cytochrome C Oxidase (COX), an enzyme responsible for ATP production and a correlate of metabolic activity, to explore functional energetic differences in HR/LR early postnatal brain. We found that HR rats display higher COX activity in the amygdala and specific hippocampal subregions compared to LRs during the first 2 weeks of life. Correlational analysis examining COX levels across several brain regions and multiple early postnatal time points suggested desynchronization in the developmental timeline of the limbic HR versus LR brain during the first two postnatal weeks. These early divergent COX activity levels may reflect altered circuitry or synaptic activity in the early postnatal HR/LR brain, which could contribute to the emergence of their distinct behavioral phenotypes. PMID:26979051
Holmes, Gregory L.; Tian, Chengju; Hernan, Amanda E.; Flynn, Sean; Camp, Devon; Barry, Jeremy
2015-01-01
There is a well-described association between infantile epilepsy and pervasive cognitive and behavioral deficits, including a high incidence of autism spectrum disorders. Despite the robustness of the relationship between early-life seizures and the development of autism, the pathophysiological mechanism by which this occurs has not been explored. As a result of increasing evidence that autism is a disorder of brain connectivity we hypothesized that early-life seizures would interrupt normal brain connectivity during brain maturation and result in an autistic phenotype. Normal rat pups underwent recurrent flurothyl-induced seizures from postnatal (P) day 5-14 and then tested, along with controls, for developmental alterations of development brain oscillatory activity from P18-25. Specifically we wished to understand how normal changes in rhythmicity in and between brain regions change as a function of age and if this rhythmicity is altered or interrupted by early life seizures. In rat pups with early-life seizures, field recordings from dorsal and ventral hippocampus and prefrontal cortex demonstrated marked increase in coherence as well as a decrease in voltage correlation at all bandwidths compared to controls while there were minimal differences in total power and relative power spectral densities. Rats with early-life seizures had resulting impairment in the sociability and social novelty tests but demonstrated no evidence of increased activity or generalized anxiety as measured in the open field. In addition, rats with early-life seizures had lower seizure thresholds than controls, indicating long-standing alterations in the excitatory/inhibition balance. Bumetanide, a pharmacological agent that blocks the activity of NKCC1 and induces a significant shift of ECl toward more hyperpolarized values, administration at the time of the seizures precluded the subsequent abnormalities in coherence and voltage correlation and resulted in normal sociability and seizure threshold. Taken together these findings indicate that early-life seizures alter the development of oscillations and result in autistic-like behaviors. The altered communication between these brain regions could reflect the physiological underpinnings underlying social cognitive deficits seen in autism spectrum disorders. PMID:25766676
Hruby, Radovan; Maas, Lili M; Fedor-Freybergh, P G
2013-01-01
The article introduces an integrative psychoneurodevelopmental model of complex human brain and mind development based on the latest findings in prenatal and perinatal medicine in terms of integrative neuroscience. The human brain development is extraordinarily complex set of events and could be influenced by a lot of factors. It is supported by new insights into the early neuro-ontogenic processes with the help of structural 3D magnetic resonance imaging or diffusion tensor imaging of fetal human brain. Various factors and targets for neural development including birth weight variability, fetal and early-life programming, fetal neurobehavioral states and fetal behavioral responses to various stimuli and others are discussed. Molecular biology reveals increasing sets of genes families as well as transcription and neurotropic factors together with critical epigenetic mechanisms to be deeply employed in the crucial neurodevelopmental events. Another field of critical importance is psychoimmuno-neuroendocrinology. Various effects of glucocorticoids as well as other hormones, prenatal stress and fetal HPA axis modulation are thought to be of special importance for brain development. The early postnatal period is characterized by the next intense shaping of complex competences, induced mainly by the very unique mother - newborn´s interactions and bonding. All these mechanisms serve to shape individual human mind with complex abilities and neurobehavioral strategies. Continuous research elucidating these special competences of human fetus and newborn/child supports integrative neuroscientific approach to involve various scientific disciplines for the next progress in human brain and mind research, and opens new scientific challenges and philosophic attitudes. New findings and approaches in this field could establish new methods in science, in primary prevention and treatment strategies, and markedly contribute to the development of modern integrative and personalized medicine.
Yamaguchi, Shinji; Hayase, Shin; Aoki, Naoya; Takehara, Akihiko; Ishigohoka, Jun; Matsushima, Toshiya; Wada, Kazuhiro; Homma, Koichi J
2017-01-01
Thyroid hormones are closely linked to the hatching process in precocial birds. Previously, we showed that thyroid hormones in brain had a strong impact on filial imprinting, an early learning behavior in newly hatched chicks; brain 3,5,3'-triiodothyronine (T3) peaks around hatching and imprinting training induces additional T3 release, thus, extending the sensitive period for imprinting and enabling subsequent other learning. On the other hand, blood thyroid hormone levels have been reported to increase gradually after hatching in altricial species, but it remains unknown how the brain thyroid hormone levels change during post-hatching development of altricial birds. Here, we determined the changes in serum and brain thyroid hormone levels of a passerine songbird species, the zebra finch using radioimmunoassay. In the serum, we found a gradual increase in thyroid hormone levels during post-hatching development, as well as differences between male and female finches. In the brain, there was clear surge in the hormone levels during development in males and females coinciding with the time of fledging, but the onset of the surge of thyroxine (T4) in males preceded that of females, whereas the onset of the surge of T3 in males succeeded that of females. These findings provide a basis for understanding the functions of thyroid hormones during early development and learning in altricial birds.
Regional infant brain development: an MRI-based morphometric analysis in 3 to 13 month olds.
Choe, Myong-Sun; Ortiz-Mantilla, Silvia; Makris, Nikos; Gregas, Matt; Bacic, Janine; Haehn, Daniel; Kennedy, David; Pienaar, Rudolph; Caviness, Verne S; Benasich, April A; Grant, P Ellen
2013-09-01
Elucidation of infant brain development is a critically important goal given the enduring impact of these early processes on various domains including later cognition and language. Although infants' whole-brain growth rates have long been available, regional growth rates have not been reported systematically. Accordingly, relatively less is known about the dynamics and organization of typically developing infant brains. Here we report global and regional volumetric growth of cerebrum, cerebellum, and brainstem with gender dimorphism, in 33 cross-sectional scans, over 3 to 13 months, using T1-weighted 3-dimensional spoiled gradient echo images and detailed semi-automated brain segmentation. Except for the midbrain and lateral ventricles, all absolute volumes of brain regions showed significant growth, with 6 different patterns of volumetric change. When normalized to the whole brain, the regional increase was characterized by 5 differential patterns. The putamen, cerebellar hemispheres, and total cerebellum were the only regions that showed positive growth in the normalized brain. Our results show region-specific patterns of volumetric change and contribute to the systematic understanding of infant brain development. This study greatly expands our knowledge of normal development and in future may provide a basis for identifying early deviation above and beyond normative variation that might signal higher risk for neurological disorders.
Regional Infant Brain Development: An MRI-Based Morphometric Analysis in 3 to 13 Month Olds
Choe, Myong-sun; Ortiz-Mantilla, Silvia; Makris, Nikos; Gregas, Matt; Bacic, Janine; Haehn, Daniel; Kennedy, David; Pienaar, Rudolph; Caviness, Verne S.; Benasich, April A.; Grant, P. Ellen
2013-01-01
Elucidation of infant brain development is a critically important goal given the enduring impact of these early processes on various domains including later cognition and language. Although infants’ whole-brain growth rates have long been available, regional growth rates have not been reported systematically. Accordingly, relatively less is known about the dynamics and organization of typically developing infant brains. Here we report global and regional volumetric growth of cerebrum, cerebellum, and brainstem with gender dimorphism, in 33 cross-sectional scans, over 3 to 13 months, using T1-weighted 3-dimensional spoiled gradient echo images and detailed semi-automated brain segmentation. Except for the midbrain and lateral ventricles, all absolute volumes of brain regions showed significant growth, with 6 different patterns of volumetric change. When normalized to the whole brain, the regional increase was characterized by 5 differential patterns. The putamen, cerebellar hemispheres, and total cerebellum were the only regions that showed positive growth in the normalized brain. Our results show region-specific patterns of volumetric change and contribute to the systematic understanding of infant brain development. This study greatly expands our knowledge of normal development and in future may provide a basis for identifying early deviation above and beyond normative variation that might signal higher risk for neurological disorders. PMID:22772652
Cunnane, Stephen C; Crawford, Michael A
2014-12-01
The human brain confronts two major challenges during its development: (i) meeting a very high energy requirement, and (ii) reliably accessing an adequate dietary source of specific brain selective nutrients needed for its structure and function. Implicitly, these energetic and nutritional constraints to normal brain development today would also have been constraints on human brain evolution. The energetic constraint was solved in large measure by the evolution in hominins of a unique and significant layer of body fat on the fetus starting during the third trimester of gestation. By providing fatty acids for ketone production that are needed as brain fuel, this fat layer supports the brain's high energy needs well into childhood. This fat layer also contains an important reserve of the brain selective omega-3 fatty acid, docosahexaenoic acid (DHA), not available in other primates. Foremost amongst the brain selective minerals are iodine and iron, with zinc, copper and selenium also being important. A shore-based diet, i.e., fish, molluscs, crustaceans, frogs, bird's eggs and aquatic plants, provides the richest known dietary sources of brain selective nutrients. Regular access to these foods by the early hominin lineage that evolved into humans would therefore have helped free the nutritional constraint on primate brain development and function. Inadequate dietary supply of brain selective nutrients still has a deleterious impact on human brain development on a global scale today, demonstrating the brain's ongoing vulnerability. The core of the shore-based paradigm of human brain evolution proposes that sustained access by certain groups of early Homo to freshwater and marine food resources would have helped surmount both the nutritional as well as the energetic constraints on mammalian brain development. Copyright © 2014 Elsevier Ltd. All rights reserved.
Investigation of brain structure in the 1-month infant.
Dean, Douglas C; Planalp, E M; Wooten, W; Schmidt, C K; Kecskemeti, S R; Frye, C; Schmidt, N L; Goldsmith, H H; Alexander, A L; Davidson, R J
2018-05-01
The developing brain undergoes systematic changes that occur at successive stages of maturation. Deviations from the typical neurodevelopmental trajectory are hypothesized to underlie many early childhood disorders; thus, characterizing the earliest patterns of normative brain development is essential. Recent neuroimaging research provides insight into brain structure during late childhood and adolescence; however, few studies have examined the infant brain, particularly in infants under 3 months of age. Using high-resolution structural MRI, we measured subcortical gray and white matter brain volumes in a cohort (N = 143) of 1-month infants and examined characteristics of these volumetric measures throughout this early period of neurodevelopment. We show that brain volumes undergo age-related changes during the first month of life, with the corresponding patterns of regional asymmetry and sexual dimorphism. Specifically, males have larger total brain volume and volumes differ by sex in regionally specific brain regions, after correcting for total brain volume. Consistent with findings from studies of later childhood and adolescence, subcortical regions appear more rightward asymmetric. Neither sex differences nor regional asymmetries changed with gestation-corrected age. Our results complement a growing body of work investigating the earliest neurobiological changes associated with development and suggest that asymmetry and sexual dimorphism are present at birth.
Kazim, Syed Faraz; Blanchard, Julie; Bianchi, Riccardo; Iqbal, Khalid
2017-01-01
Down syndrome (DS), caused by trisomy 21, is the most common genetic cause of intellectual disability and is associated with a greatly increased risk of early-onset Alzheimer’s disease (AD). The Ts65Dn mouse model of DS exhibits several key features of the disease including developmental delay and AD-like cognitive impairment. Accumulating evidence suggests that impairments in early brain development caused by trisomy 21 contribute significantly to memory deficits in adult life in DS. Prenatal genetic testing to diagnose DS in utero, provides the novel opportunity to initiate early pharmacological treatment to target this critical period of brain development. Here, we report that prenatal to early postnatal treatment with a ciliary neurotrophic factor (CNTF) small-molecule peptide mimetic, Peptide 021 (P021), rescued developmental delay in pups and AD-like hippocampus-dependent memory impairments in adult life in Ts65Dn mice. Furthermore, this treatment prevented pre-synaptic protein deficit, decreased glycogen synthase kinase-3beta (GSK3β) activity, and increased levels of synaptic plasticity markers including brain derived neurotrophic factor (BNDF) and phosphorylated CREB, both in young (3-week-old) and adult (~ 7-month-old) Ts65Dn mice. These findings provide novel evidence that providing neurotrophic support during early brain development can prevent developmental delay and AD-like memory impairments in a DS mouse model. PMID:28368015
Luby, Joan; Belden, Andy; Botteron, Kelly; Marrus, Natasha; Harms, Michael P; Babb, Casey; Nishino, Tomoyuki; Barch, Deanna
2013-12-01
IMPORTANCE The study provides novel data to inform the mechanisms by which poverty negatively impacts childhood brain development. OBJECTIVE To investigate whether the income-to-needs ratio experienced in early childhood impacts brain development at school age and to explore the mediators of this effect. DESIGN, SETTING, AND PARTICIPANTS This study was conducted at an academic research unit at the Washington University School of Medicine in St Louis. Data from a prospective longitudinal study of emotion development in preschool children who participated in neuroimaging at school age were used to investigate the effects of poverty on brain development. Children were assessed annually for 3 to 6 years prior to the time of a magnetic resonance imaging scan, during which they were evaluated on psychosocial, behavioral, and other developmental dimensions. Preschoolers included in the study were 3 to 6 years of age and were recruited from primary care and day care sites in the St Louis metropolitan area; they were annually assessed behaviorally for 5 to 10 years. Healthy preschoolers and those with clinical symptoms of depression participated in neuroimaging at school age/early adolescence. EXPOSURE Household poverty as measured by the income-to-needs ratio. MAIN OUTCOMES AND MEASURES Brain volumes of children's white matter and cortical gray matter, as well as hippocampus and amygdala volumes, obtained using magnetic resonance imaging. Mediators of interest were caregiver support/hostility measured observationally during the preschool period and stressful life events measured prospectively. RESULTS Poverty was associated with smaller white and cortical gray matter and hippocampal and amygdala volumes. The effects of poverty on hippocampal volume were mediated by caregiving support/hostility on the left and right, as well as stressful life events on the left. CONCLUSIONS AND RELEVANCE The finding that exposure to poverty in early childhood materially impacts brain development at school age further underscores the importance of attention to the well-established deleterious effects of poverty on child development. Findings that these effects on the hippocampus are mediated by caregiving and stressful life events suggest that attempts to enhance early caregiving should be a focused public health target for prevention and early intervention. Findings substantiate the behavioral literature on the negative effects of poverty on child development and provide new data confirming that effects extend to brain development. Mechanisms for these effects on the hippocampus are suggested to inform intervention.
ALL OUR SONS: THE DEVELOPMENTAL NEUROBIOLOGY AND NEUROENDOCRINOLOGY OF BOYS AT RISK.
Schore, Allan N
2017-01-01
Why are boys at risk? To address this question, I use the perspective of regulation theory to offer a model of the deeper psychoneurobiological mechanisms that underlie the vulnerability of the developing male. The central thesis of this work dictates that significant gender differences are seen between male and female social and emotional functions in the earliest stages of development, and that these result from not only differences in sex hormones and social experiences but also in rates of male and female brain maturation, specifically in the early developing right brain. I present interdisciplinary research which indicates that the stress-regulating circuits of the male brain mature more slowly than those of the female in the prenatal, perinatal, and postnatal critical periods, and that this differential structural maturation is reflected in normal gender differences in right-brain attachment functions. Due to this maturational delay, developing males also are more vulnerable over a longer period of time to stressors in the social environment (attachment trauma) and toxins in the physical environment (endocrine disruptors) that negatively impact right-brain development. In terms of differences in gender-related psychopathology, I describe the early developmental neuroendocrinological and neurobiological mechanisms that are involved in the increased vulnerability of males to autism, early onset schizophrenia, attention deficit hyperactivity disorder, and conduct disorders as well as the epigenetic mechanisms that can account for the recent widespread increase of these disorders in U.S. culture. I also offer a clinical formulation of early assessments of boys at risk, discuss the impact of early childcare on male psychopathogenesis, and end with a neurobiological model of optimal adult male socioemotional functions. © 2017 Michigan Association for Infant Mental Health.
Korevaar, Tim I M; Tiemeier, Henning; Peeters, Robin P
2018-04-24
Thyroid hormone is an important regulator of early brain development, particularly during early stages of gestation during which foetal thyroid hormone availability depends on the maternal transfer of thyroid hormones. There is a wide range of experimental studies showing that low maternal thyroid hormone availability is associated with suboptimal brain development parameters. While few clinical studies have shown that overt maternal hypothyroidism is associated with lower child IQ, the question whether more subclinical changes in maternal thyroid function could also lead to suboptimal foetal brain development. In this review, we put the latter studies in perspective and discuss their interpretation from an epidemiological and clinical perspective. Furthermore, we extend this discussion to also include future perspective and identify important knowledge gaps in the field. © 2018 John Wiley & Sons Ltd.
Margherio, Cara; Horner-Devine, M. Claire; Mizumori, Sheri J. Y.; Yen, Joyce W.
2016-01-01
BRAINS: Broadening the Representation of Academic Investigators in NeuroScience is a National Institutes of Health–funded, national program that addresses challenges to the persistence of diverse early-career neuroscientists. In doing so, BRAINS aims to advance diversity in neuroscience by increasing career advancement and retention of post-PhD, early-career neuroscientists from underrepresented groups (URGs). The comprehensive professional development program is structured to catalyze conversations specific to URGs in neuroscience and explicitly addresses factors known to impact persistence such as a weak sense of belonging to the scientific community, isolation and solo status, inequitable access to resources that impact career success, and marginalization from informal networks and mentoring relationships. While we do not yet have data on the long-term impact of the BRAINS program on participants’ career trajectory and persistence, we introduce the BRAINS program theory and report early quantitative and qualitative data on shorter-term individual impacts within the realms of career-advancing behaviors and career experiences. These early results suggest promising, positive career productivity, increased self-efficacy, stronger sense of belonging, and new perspectives on navigating careers for BRAINS participants. We finish by discussing recommendations for future professional development programs and research designed to broaden participation in the biomedical and life sciences. PMID:27587858
Network Analysis: Applications for the Developing Brain
Chu-Shore, Catherine J.; Kramer, Mark A.; Bianchi, Matt T.; Caviness, Verne S.; Cash, Sydney S.
2011-01-01
Development of the human brain follows a complex trajectory of age-specific anatomical and physiological changes. The application of network analysis provides an illuminating perspective on the dynamic interregional and global properties of this intricate and complex system. Here, we provide a critical synopsis of methods of network analysis with a focus on developing brain networks. After discussing basic concepts and approaches to network analysis, we explore the primary events of anatomical cortical development from gestation through adolescence. Upon this framework, we describe early work revealing the evolution of age-specific functional brain networks in normal neurodevelopment. Finally, we review how these relationships can be altered in disease and perhaps even rectified with treatment. While this method of description and inquiry remains in early form, there is already substantial evidence that the application of network models and analysis to understanding normal and abnormal human neural development holds tremendous promise for future discovery. PMID:21303762
Traumatic Brain Injury in Early Childhood: Developmental Effects and Interventions.
ERIC Educational Resources Information Center
Lowenthal, Barbara; Lowenthal, Barbara
1998-01-01
Describes the unique effects of traumatic brain injury (TBI) on development in early childhood and offers suggestions for interventions in the cognitive, language, social-emotional, motor, and adaptive domains. Urges more intensive, long-term studies on the immediate and long-term effects of TBI. (Author/DB)
Cloarec, Robin; Bauer, Sylvian; Teissier, Natacha; Schaller, Fabienne; Luche, Hervé; Courtens, Sandra; Salmi, Manal; Pauly, Vanessa; Bois, Emilie; Pallesi-Pocachard, Emilie; Buhler, Emmanuelle; Michel, François J.; Gressens, Pierre; Malissen, Marie; Stamminger, Thomas; Streblow, Daniel N.; Bruneau, Nadine; Szepetowski, Pierre
2018-01-01
Congenital cytomegalovirus (CMV) infections represent one leading cause of neurodevelopmental disorders. Recently, we reported on a rat model of CMV infection of the developing brain in utero, characterized by early and prominent infection and alteration of microglia—the brain-resident mononuclear phagocytes. Besides their canonical function against pathogens, microglia are also pivotal to brain development. Here we show that CMV infection of the rat fetal brain recapitulated key postnatal phenotypes of human congenital CMV including increased mortality, sensorimotor impairment reminiscent of cerebral palsy, hearing defects, and epileptic seizures. The possible influence of early microglia alteration on those phenotypes was then questioned by pharmacological targeting of microglia during pregnancy. One single administration of clodronate liposomes in the embryonic brains at the time of CMV injection to deplete microglia, and maternal feeding with doxycyxline throughout pregnancy to modify microglia in the litters' brains, were both associated with dramatic improvements of survival, body weight gain, sensorimotor development and with decreased risk of epileptic seizures. Improvement of microglia activation status did not persist postnatally after doxycycline discontinuation; also, active brain infection remained unchanged by doxycycline. Altogether our data indicate that early microglia alteration, rather than brain CMV load per se, is instrumental in influencing survival and the neurological outcomes of CMV-infected rats, and suggest that microglia might participate in the neurological outcome of congenital CMV in humans. Furthermore this study represents a first proof-of-principle for the design of microglia-targeted preventive strategies in the context of congenital CMV infection of the brain. PMID:29559892
Lupien, Sonia J; Juster, Robert-Paul; Raymond, Catherine; Marin, Marie-France
2018-04-01
For the last five decades, science has managed to delineate the mechanisms by which stress hormones can impact on the human brain. Receptors for glucocorticoids are found in the hippocampus, amygdala and frontal cortex, three brain regions involved in memory processing and emotional regulation. Studies have shown that chronic exposure to stress is associated with reduced volume of the hippocampus and that chronic stress can modulate volumes of both the amygdala and frontal cortex, suggesting neurotoxic effects of stress hormones on the brain. Yet, other studies report that exposure to early adversity and/or familial/social stressors can increase vulnerability to stress in adulthood. Models have been recently developed to describe the roles that neurotoxic and vulnerability effects can have on the developing brain. These models suggest that developing early stress interventions could potentially counteract the effects of chronic stress on the brain and results going along with this hypothesis are summarized. Copyright © 2018 Elsevier Inc. All rights reserved.
Phonation takes precedence over articulation in development as well as evolution of language.
Oller, D Kimbrough
2014-12-01
Early human vocal development is characterized first by emerging control of phonation and later by prosodic and supraglottal articulation. The target article has missed the opportunity to use these facts in the characterization of evolution in language-specific brain mechanisms. Phonation appears to be the initial human-specific brain change for language, and it was presumably a key target of selection in early hominin evolution.
Challenges and Limitations in Early Intervention
ERIC Educational Resources Information Center
Hadders-Algra, Mijna
2011-01-01
Research over the past three decades has shown that early intervention in infants biologically at risk of developmental disorders, irrespective of the presence of a brain lesion, is associated with improved cognitive development in early childhood without affecting motor development. However, at present it is unknown whether early intervention is…
Converging early responses to brain injury pave the road to epileptogenesis.
Neuberger, Eric J; Gupta, Akshay; Subramanian, Deepak; Korgaonkar, Akshata A; Santhakumar, Vijayalakshmi
2017-11-29
Epilepsy, characterized by recurrent seizures and abnormal electrical activity in the brain, is one of the most prevalent brain disorders. Over two million people in the United States have been diagnosed with epilepsy and 3% of the general population will be diagnosed with it at some point in their lives. While most developmental epilepsies occur due to genetic predisposition, a class of "acquired" epilepsies results from a variety of brain insults. A leading etiological factor for epilepsy that is currently on the rise is traumatic brain injury (TBI), which accounts for up to 20% of all symptomatic epilepsies. Remarkably, the presence of an identified early insult that constitutes a risk for development of epilepsy provides a therapeutic window in which the pathological processes associated with brain injury can be manipulated to limit the subsequent development of recurrent seizure activity and epilepsy. Recent studies have revealed diverse pathologies, including enhanced excitability, activated immune signaling, cell death, and enhanced neurogenesis within a week after injury, suggesting a period of heightened adaptive and maladaptive plasticity. An integrated understanding of these processes and their cellular and molecular underpinnings could lead to novel targets to arrest epileptogenesis after trauma. This review attempts to highlight and relate the diverse early changes after trauma and their role in development of epilepsy and suggests potential strategies to limit neurological complications in the injured brain. © 2017 Wiley Periodicals, Inc.
ERIC Educational Resources Information Center
Ozcaliskan, Seyda; Levine, Susan C.; Goldin-Meadow, Susan
2013-01-01
Children with pre/perinatal unilateral brain lesions (PL) show remarkable plasticity for language development. Is this plasticity characterized by the same developmental trajectory that characterizes typically developing (TD) children, with gesture leading the way into speech? We explored this question, comparing eleven children with PL -- matched…
Van Herck, Stijn L J; Delbaere, Joke; Bourgeois, Nele M A; McAllan, Bronwyn M; Richardson, Samantha J; Darras, Veerle M
2015-04-01
Thyroid hormones (THs) are key regulators in the development of the vertebrate brain. Therefore, TH access to the developing brain needs to be strictly regulated. The brain barriers separate the central nervous system from the rest of the body and impose specific transport mechanisms on the exchange of molecules between the general circulation and the nervous system. As such they form ideal structures for regulating TH exchange between the blood and the brain. To investigate the mechanism by which the developing brain regulates TH availability, we investigated the ontogenetic expression profiles of TH transporters, deiodinases and the TH distributor protein transthyretin (TTR) at the brain barriers during embryonic and early postnatal development using the chicken as a model. In situ hybridisation revealed expression of the TH transporters monocarboxylate transporter 8 (MCT8) and 10 (MCT10), organic anion transporting polypeptide 1C1 (OATP1C1) and L-type amino acid transporter 1 (LAT1) and the inactivating type 3 deiodinase (D3) in the choroid plexus which forms the blood-cerebrospinal fluid barrier. This was confirmed by quantitative PCR which additionally indicated strongly increasing expression of TTR as well as detectable expression of the activating type 2 deiodinase (D2) and the (in)activating type 1 deiodinase (D1). In the brain capillaries forming the blood-brain barrier in situ hybridisation showed exclusive expression of LAT1 and D2. The combined presence of LAT1 and D2 in brain capillaries suggests that the blood-brain barrier forms the main route for receptor-active T3 uptake into the embryonic chicken brain. Expression of multiple transporters, deiodinases and TTR in the choroid plexus indicates that the blood-cerebrospinal fluid barrier is also important in regulating early TH availability. The impact of these barrier systems can be deduced from the clear difference in T3 and T4 levels as well as the T3/T4 ratio between the developing brain and the general circulation. We conclude that the tight regulation of TH exchange at the brain barriers from early embryonic stages is one of the factors needed to allow the brain to develop within a relative microenvironment. Copyright © 2015 Elsevier Inc. All rights reserved.
QUANTITATIVE PROCEDURES FOR NEUROTOXICOLOGY RISK ASSESSMENT
In this project, previously published information on biologically based dose-response model for brain development was used to quantitatively evaluate critical neurodevelopmental processes, and to assess potential chemical impacts on early brain development. This model has been ex...
Tanaka, Chiaki; Matsui, Mie; Uematsu, Akiko; Noguchi, Kyo; Miyawaki, Toshio
2012-01-01
Brain development during early life in healthy individuals is rapid and dynamic, indicating that this period plays a very important role in neural and functional development. The frontal and temporal lobes are known to play a particularly important role in cognition. The study of healthy frontal and temporal lobe development in children is therefore of considerable importance. A better understanding of how these brain regions develop could also aid in the diagnosis and treatment of neurodevelopmental disorders. Some developmental studies have used magnetic resonance imaging (MRI) to examine infant brains, but it remains the case that relatively little is known about cortical brain development in the first few years of life. In the present study we examined whole brain, temporal lobe and frontal lobe developmental trajectories from infancy to early adulthood in healthy individuals, considering gender and brain hemisphere differences. We performed a cross-sectional, longitudinal morphometric MRI study of 114 healthy individuals (54 females and 60 males) aged 1 month to 25 years old (mean age ± SD 8.8 ± 6.9). We measured whole brain, temporal and frontal lobe gray matter (GM)/white matter (WM) volumes, following previously used protocols. There were significant non-linear age-related volume changes in all regions. Peak ages of whole brain, temporal lobe and frontal lobe development occurred around pre-adolescence (9-12 years old). GM volumes for all regions increased significantly as a function of age. Peak age was nevertheless lobe specific, with a pattern of earlier peak ages for females in both temporal and frontal lobes. Growth change in whole brain GM volume was larger in males than in females. However, GM volume growth changes for the temporal and frontal lobes showed a somewhat different pattern. GM volume for both temporal and frontal lobes showed a greater increase in females until around 5-6 years old, at which point this tendency reversed (GM volume changes in males became greater), with male GM volume increasing for a longer time than that of females. WM volume growth changes were similar across regions, all increasing rapidly until early childhood but slowing down thereafter. All regions displayed significant rightward volumetric asymmetry regardless of sex. Furthermore, the right temporal and frontal lobes showed a greater volumetric increase than the left for the first several years, with this tendency reversing at around 6 years of age. In addition, the left frontal and temporal lobes increased in volume for a longer period of time. Taken together, these findings indicated that brain developmental trajectories differ depending on brain region, sex and brain hemisphere. Gender-related factors such as sex hormones and functional laterality may affect brain development. Copyright © 2012 S. Karger AG, Basel.
"Use-It-or-Lose-It"? Interrogating an Educational Message from Teen Brain Research
ERIC Educational Resources Information Center
Payne, Monica A.
2010-01-01
Recent neuroimaging research has encouraged a fundamental shift in psychological thinking about cognitive development in adolescence. Challenging the existing view that early childhood was the most critical period for intellectually hard-wiring the brain, findings led researchers to speculate that early adolescence might be the more important…
Lenz, Kathryn M; Nelson, Lars H
2018-01-01
Innate immune cells play a well-documented role in the etiology and disease course of many brain-based conditions, including multiple sclerosis, Alzheimer's disease, traumatic brain and spinal cord injury, and brain cancers. In contrast, it is only recently becoming clear that innate immune cells, primarily brain resident macrophages called microglia, are also key regulators of brain development. This review summarizes the current state of knowledge regarding microglia in brain development, with particular emphasis on how microglia during development are distinct from microglia later in life. We also summarize the effects of early life perturbations on microglia function in the developing brain, the role that biological sex plays in microglia function, and the potential role that microglia may play in developmental brain disorders. Finally, given how new the field of developmental neuroimmunology is, we highlight what has yet to be learned about how innate immune cells shape the development of brain and behavior.
Ohta, Ken-Ichi; Suzuki, Shingo; Warita, Katsuhiko; Kaji, Tomohiro; Kusaka, Takashi; Miki, Takanori
2017-04-01
Maternal separation (MS) is known to affect hippocampal function such as learning and memory, yet the molecular mechanism remains unknown. We hypothesized that these impairments are attributed to abnormities of neural circuit formation by MS, and focused on brain-derived neurotrophic factor (BDNF) as key factor because BDNF signaling has an essential role in synapse formation during early brain development. Using rat offspring exposed to MS for 6 h/day during postnatal days (PD) 2-20, we estimated BDNF signaling in the hippocampus during brain development. Our results show that MS attenuated BDNF expression and activation of extracellular signal-regulated kinase (ERK) around PD 7. Moreover, plasticity-related immediate early genes, which are transcriptionally regulated by BDNF-ERK signaling, were also reduced by MS around PD 7. Interestingly, detailed analysis revealed that MS particularly reduced expression of BDNF gene and immediate early genes in the cornu ammonis 1 (CA1) of hippocampus at PD 7. Considering that BDNF-ERK signaling is involved in spine formation, we next evaluated spine formation in the hippocampus during the weaning period. Our results show that MS particularly reduced mature spine density in proximal apical dendrites of CA1 pyramidal neurons at PD 21. These results suggest that MS could attenuate BDNF-ERK signaling during primary synaptogenesis with a region-specific manner, which is likely to lead to decreased spine formation and maturation observed in the hippocampal CA1 region. It is speculated that this incomplete spine formation during early brain development has an influence on learning capabilities throughout adulthood. © 2017 International Society for Neurochemistry.
Genetic and Diagnostic Biomarker Development in ASD Toddlers Using Resting State Functional MRI
2016-09-01
networks during resting states. Autism spectrum disorder (ASD) begins prenatal, and early maldevelopment is present in many sites and systems that mediate...molecular and genomic evidence indicates autism spectrum disorder (ASD) begins prenatally, most likely by or before the late second trimester 10-15 as...ages 3 to 4 years. 2. KEYWORDS Autism spectrum disorder, ASD, early brain development, intrinsic functional brain networks, fMRI, infants, toddlers
Early Language Learning and Literacy: Neuroscience Implications for Education
Kuhl, Patricia K.
2011-01-01
The last decade has produced an explosion in neuroscience research examining young children’s early processing of language that has implications for education. Noninvasive, safe functional brain measurements have now been proven feasible for use with children starting at birth. In the arena of language, the neural signatures of learning can be documented at a remarkably early point in development, and these early measures predict performance in children’s language and pre-reading abilities in the second, third, and fifth year of life, a finding with theoretical and educational import. There is evidence that children’s early mastery of language requires learning in a social context, and this finding also has important implications for education. Evidence relating socio-economic status (SES) to brain function for language suggests that SES should be considered a proxy for the opportunity to learn and that the complexity of language input is a significant factor in developing brain areas related to language. The data indicate that the opportunity to learn from complex stimuli and events are vital early in life, and that success in school begins in infancy. PMID:21892359
Early embryonic brain development in rats requires the trophic influence of cerebrospinal fluid.
Martin, C; Alonso, M I; Santiago, C; Moro, J A; De la Mano, A; Carretero, R; Gato, A
2009-11-01
Cerebrospinal fluid has shown itself to be an essential brain component during development. This is particularly evident at the earliest stages of development where a lot of research, performed mainly in chick embryos, supports the evidence that cerebrospinal fluid is involved in different mechanisms controlling brain growth and morphogenesis, by exerting a trophic effect on neuroepithelial precursor cells (NPC) involved in controlling the behaviour of these cells. Despite it being known that cerebrospinal fluid in mammals is directly involved in corticogenesis at fetal stages, the influence of cerebrospinal fluid on the activity of NPC at the earliest stages of brain development has not been demonstrated. Here, using "in vitro" organotypic cultures of rat embryo brain neuroepithelium in order to expose NPC to or deprive them of cerebrospinal fluid, we show that the neuroepithelium needs the trophic influence of cerebrospinal fluid to undergo normal rates of cell survival, replication and neurogenesis, suggesting that NPC are not self-sufficient to induce their normal activity. This data shows that cerebrospinal fluid is an essential component in chick and rat early brain development, suggesting that its influence could be constant in higher vertebrates.
Booij, Linda; Tremblay, Richard E.; Szyf, Moshe; Benkelfat, Chawki
2015-01-01
Background Despite more than 60 years of research in the role of serotonin (5-HT) in psychopathology, many questions still remain. From a developmental perspective, studies have provided more insight into how 5-HT dysfunctions acquired in utero or early in life may modulate brain development. This paper discusses the relevance of the developmental role of 5-HT for the understanding of psychopathology. We review developmental milestones of the 5-HT system, how genetic and environmental 5-HT disturbances could affect brain development and the potential role of DNA methylation in 5-HT genes for brain development. Methods Studies were identified using common databases (e.g., PubMed, Google Scholar) and reference lists. Results Despite the widely supported view that the 5-HT system matures in early life, different 5-HT receptors, proteins and enzymes have different developmental patterns, and development is brain region–specific. A disruption in 5-HT homeostasis during development may lead to structural and functional changes in brain circuits that modulate emotional stress responses, including subcortical limbic and (pre)frontal areas. This may result in a predisposition to psychopathology. DNA methylation might be one of the underlying physiologic mechanisms. Limitations There is a need for prospective studies. The impact of stressors during adolescence on the 5-HT system is understudied. Questions regarding efficacy of drugs acting on 5-HT still remain. Conclusion A multidisciplinary and longitudinal approach in designing studies on the role of 5-HT in psychopathology might help to bring us closer to the understanding of the role of 5-HT in psychopathology. PMID:25285876
Sullivan, Regina; Wilson, Donald A.; Feldon, Joram; Yee, Benjamin K.; Meyer, Urs; Richter-Levin, Gal; Avi, Avital; Michael, Tsoory; Gruss, Michael; Bock, Jörg; Helmeke, Carina; Braun, Katharina
2007-01-01
Decades of research in the area of developmental psychobiology have shown that early life experience alters behavioral and brain development, which canalizes development to suit different environments. Recent methodological advances have begun to identify the mechanisms by which early life experiences cause these diverse adult outcomes. Here we present four different research programs that demonstrate the intricacies of early environmental influences on behavioral and brain development in both pathological and normal development. First, an animal model of schizophrenia is presented that suggests prenatal immune stimulation influences the postpubertal emergence of psychosis-related behavior in mice. Second, we describe a research program on infant rats that demonstrates how early odor learning has unique characteristics due to the unique functioning of the infant limbic system. Third, we present work on the rodent Octodon degus, which shows that early paternal and/or maternal deprivation alters development of limbic system synaptic density that corresponds to heightened emotionality. Fourth, ajuvenile model of stress is presented that suggests this developmental period is important in determining adulthood emotional well being. The approach of each research program is strikingly different, yet all succeed in delineating a specific aspect of early development and its effects on infant and adult outcome that expands our understanding of the developmental impact of infant experiences on emotional and limbic system development. Together, these research programs suggest that the developing organism’s developmental trajectory is influenced by environmental factors beginning in the fetus and extending through adolescence, although the specific timing and nature of the environmental influence has unique impact on adult mental health. PMID:17016842
Age-related functional brain changes in young children.
Long, Xiangyu; Benischek, Alina; Dewey, Deborah; Lebel, Catherine
2017-07-15
Brain function and structure change significantly during the toddler and preschool years. However, most studies focus on older or younger children, so the specific nature of these changes is unclear. In the present study, we analyzed 77 functional magnetic resonance imaging datasets from 44 children aged 2-6 years. We extracted measures of both local (amplitude of low frequency fluctuation and regional homogeneity) and global (eigenvector centrality mapping) activity and connectivity, and examined their relationships with age using robust linear correlation analysis and strict control for head motion. Brain areas within the default mode network and the frontoparietal network, such as the middle frontal gyrus, the inferior parietal lobule and the posterior cingulate cortex, showed increases in local and global functional features with age. Several brain areas such as the superior parietal lobule and superior temporal gyrus presented opposite development trajectories of local and global functional features, suggesting a shifting connectivity framework in early childhood. This development of functional connectivity in early childhood likely underlies major advances in cognitive abilities, including language and development of theory of mind. These findings provide important insight into the development patterns of brain function during the preschool years, and lay the foundation for future studies of altered brain development in young children with brain disorders or injury. Copyright © 2017 Elsevier Inc. All rights reserved.
ERIC Educational Resources Information Center
Westmacott, Robyn; Askalan, Rand; MacGregor, Daune; Anderson, Peter; deVeber, Gabrielle
2010-01-01
Aim: Plasticity in the developing brain is a controversial issue. Although language and motor function often recover remarkably well following early brain injury, recent evidence suggests that damage to the developing brain results in significant long-term neuropsychological impairment. Our aim was to investigate the relationship among age at…
Primary cortical folding in the human newborn: an early marker of later functional development.
Dubois, J; Benders, M; Borradori-Tolsa, C; Cachia, A; Lazeyras, F; Ha-Vinh Leuchter, R; Sizonenko, S V; Warfield, S K; Mangin, J F; Hüppi, P S
2008-08-01
In the human brain, the morphology of cortical gyri and sulci is complex and variable among individuals, and it may reflect pathological functioning with specific abnormalities observed in certain developmental and neuropsychiatric disorders. Since cortical folding occurs early during brain development, these structural abnormalities might be present long before the appearance of functional symptoms. So far, the precise mechanisms responsible for such alteration in the convolution pattern during intra-uterine or post-natal development are still poorly understood. Here we compared anatomical and functional brain development in vivo among 45 premature newborns who experienced different intra-uterine environments: 22 normal singletons, 12 twins and 11 newborns with intrauterine growth restriction (IUGR). Using magnetic resonance imaging (MRI) and dedicated post-processing tools, we investigated early disturbances in cortical formation at birth, over the developmental period critical for the emergence of convolutions (26-36 weeks of gestational age), and defined early 'endophenotypes' of sulcal development. We demonstrated that twins have a delayed but harmonious maturation, with reduced surface and sulcation index compared to singletons, whereas the gyrification of IUGR newborns is discordant to the normal developmental trajectory, with a more pronounced reduction of surface in relation to the sulcation index compared to normal newborns. Furthermore, we showed that these structural measurements of the brain at birth are predictors of infants' outcome at term equivalent age, for MRI-based cerebral volumes and neurobehavioural development evaluated with the assessment of preterm infant's behaviour (APIB).
Cranial thickness changes in early childhood
NASA Astrophysics Data System (ADS)
Gajawelli, Niharika; Deoni, Sean; Shi, Jie; Dirks, Holly; Linguraru, Marius George; Nelson, Marvin D.; Wang, Yalin; Lepore, Natasha
2017-11-01
The neurocranium changes rapidly in early childhood to accommodate the developing brain. However, developmental disorders may cause abnormal growth of the neurocranium, the most common one being craniosynostosis, affecting about 1 in 2000 children. It is important to understand how the brain and neurocranium develop together to understand the role of the neurocranium in neurodevelopmental outcomes. However, the neurocranium is not as well studied as the human brain in early childhood, due to a lack of imaging data. CT is typically employed to investigate the cranium, but, due to ionizing radiation, may only be used for clinical cases. However, the neurocranium is also visible on magnetic resonance imaging (MRI). Here, we used a large dataset of MRI images from healthy children in the age range of 1 to 2 years old and extracted the neurocranium. A conformal geometry based analysis pipeline is implemented to determine a set of statistical atlases of the neurocranium. A growth model of the neurocranium will help us understand cranial bone and suture development with respect to the brain, which will in turn inform better treatment strategies for neurocranial disorders.
White matter maturation profiles through early childhood predict general cognitive ability.
Deoni, Sean C L; O'Muircheartaigh, Jonathan; Elison, Jed T; Walker, Lindsay; Doernberg, Ellen; Waskiewicz, Nicole; Dirks, Holly; Piryatinsky, Irene; Dean, Doug C; Jumbe, N L
2016-03-01
Infancy and early childhood are periods of rapid brain development, during which brain structure and function mature alongside evolving cognitive ability. An important neurodevelopmental process during this postnatal period is the maturation of the myelinated white matter, which facilitates rapid communication across neural systems and networks. Though prior brain imaging studies in children (4 years of age and above), adolescents, and adults have consistently linked white matter development with cognitive maturation and intelligence, few studies have examined how these processes are related throughout early development (birth to 4 years of age). Here, we show that the profile of white matter myelination across the first 5 years of life is strongly and specifically related to cognitive ability. Using a longitudinal design, coupled with advanced magnetic resonance imaging, we demonstrate that children with above-average ability show differential trajectories of myelin development compared to average and below average ability children, even when controlling for socioeconomic status, gestation, and birth weight. Specifically, higher ability children exhibit slower but more prolonged early development, resulting in overall increased myelin measures by ~3 years of age. These results provide new insight into the early neuroanatomical correlates of cognitive ability, and suggest an early period of prolonged maturation with associated protracted white matter plasticity may result in strengthened neural networks that can better support later development. Further, these results reinforce the necessity of a longitudinal perspective in investigating typical or suspected atypical cognitive maturation.
Zuk, Jennifer; Gaab, Nadine
2018-05-24
The study of music training as a model for structural plasticity has evolved significantly over the past 15 years. Neuroimaging studies have identified characteristic structural brain alterations in musicians compared to nonmusicians in school-age children and adults, using primarily cross-sectional designs. Despite this emerging evidence and advances in pediatric neuroimaging techniques, hardly any studies have examined brain development in early childhood (before age 8) in association with musical training, and longitudinal studies starting in infancy or preschool are particularly scarce. Consequently, it remains unclear whether the characteristic "musician brain" is solely the result of musical training, or whether certain predispositions may have an impact on its development. Moving toward a developmental perspective, the present review considers various factors that may contribute to early brain structure prior to the onset of formal musical training. This review introduces a model for potential neurobiological pathways leading to the characteristic "musician brain," which involves a developmental interaction between predisposition and its temporal dynamics, environmental experience, and training-induced plasticity. This perspective illuminates the importance of studying the brain structure associated with musical training through a developmental lens, and the need for longitudinal studies in early childhood to advance our understanding of music training-induced structural plasticity. © 2018 New York Academy of Sciences.
Want Success in School? Start with Babies!
ERIC Educational Resources Information Center
Lally, J. Ronald
2012-01-01
Much of what gets in the way of learning in elementary, middle, and high schools has to do with lessons missed, skills undeveloped, and experiences in the world that have shaped the early development of the brain. Neuroscience tells people that early experience, even experience in the womb, is the soil in which the young brain grows and that early…
ERIC Educational Resources Information Center
Ray, Marcy, Ed.
2006-01-01
In this interview, Council member William Greenough discusses the need for rich, complex experiences combined with physical activity in early childhood to help build a strong foundation for learning. He explains how rich, complex experiences are necessary for the development of sound brain architecture, particularly during early childhood, but…
Understanding and Promoting Resilience in the Context of Adverse Childhood Experiences
ERIC Educational Resources Information Center
Sciaraffa, Mary A.; Zeanah, Paula D.; Zeanah, Charles H.
2018-01-01
Brain development in the early years is especially susceptible to toxic stress caused by adverse childhood experiences (ACEs). According to epigenetics research, toxic stress has the capacity to physically change a child's brain and be hardwired into the child's biology via genes in the DNA. The compelling nature of the impact of early adversity…
Kozberg, Mariel G; Ma, Ying; Shaik, Mohammed A; Kim, Sharon H; Hillman, Elizabeth M C
2016-06-22
In the adult brain, increases in neural activity lead to increases in local blood flow. However, many prior measurements of functional hemodynamics in the neonatal brain, including functional magnetic resonance imaging (fMRI) in human infants, have noted altered and even inverted hemodynamic responses to stimuli. Here, we demonstrate that localized neural activity in early postnatal mice does not evoke blood flow increases as in the adult brain, and elucidate the neural and metabolic correlates of these altered functional hemodynamics as a function of developmental age. Using wide-field GCaMP imaging, the development of neural responses to somatosensory stimulus is visualized over the entire bilaterally exposed cortex. Neural responses are observed to progress from tightly localized, unilateral maps to bilateral responses as interhemispheric connectivity becomes established. Simultaneous hemodynamic imaging confirms that spatiotemporally coupled functional hyperemia is not present during these early stages of postnatal brain development, and develops gradually as cortical connectivity is established. Exploring the consequences of this lack of functional hyperemia, measurements of oxidative metabolism via flavoprotein fluorescence suggest that neural activity depletes local oxygen to below baseline levels at early developmental stages. Analysis of hemoglobin oxygenation dynamics at the same age confirms oxygen depletion for both stimulus-evoked and resting-state neural activity. This state of unmet metabolic demand during neural network development poses new questions about the mechanisms of neurovascular development and its role in both normal and abnormal brain development. These results also provide important insights for the interpretation of fMRI studies of the developing brain. This work demonstrates that the postnatal development of neuronal connectivity is accompanied by development of the mechanisms that regulate local blood flow in response to neural activity. Novel in vivo imaging reveals that, in the developing mouse brain, strong and localized GCaMP neural responses to stimulus fail to evoke local blood flow increases, leading to a state in which oxygen levels become locally depleted. These results demonstrate that the development of cortical connectivity occurs in an environment of altered energy availability that itself may play a role in shaping normal brain development. These findings have important implications for understanding the pathophysiology of abnormal developmental trajectories, and for the interpretation of functional magnetic resonance imaging data acquired in the developing brain. Copyright © 2016 the authors 0270-6474/16/366704-14$15.00/0.
The effects of musical training on structural brain development: a longitudinal study.
Hyde, Krista L; Lerch, Jason; Norton, Andrea; Forgeard, Marie; Winner, Ellen; Evans, Alan C; Schlaug, Gottfried
2009-07-01
Long-term instrumental music training is an intense, multisensory and motor experience that offers an ideal opportunity to study structural brain plasticity in the developing brain in correlation with behavioral changes induced by training. Here, for the first time, we demonstrate structural brain changes after only 15 months of musical training in early childhood, which were correlated with improvements in musically relevant motor and auditory skills. These findings shed light on brain plasticity, and suggest that structural brain differences in adult experts (whether musicians or experts in other areas) are likely due to training-induced brain plasticity.
Early behavioral intervention, brain plasticity, and the prevention of autism spectrum disorder.
Dawson, Geraldine
2008-01-01
Advances in the fields of cognitive and affective developmental neuroscience, developmental psychopathology, neurobiology, genetics, and applied behavior analysis have contributed to a more optimistic outcome for individuals with autism spectrum disorder (ASD). These advances have led to new methods for early detection and more effective treatments. For the first time, prevention of ASD is plausible. Prevention will entail detecting infants at risk before the full syndrome is present and implementing treatments designed to alter the course of early behavioral and brain development. This article describes a developmental model of risk, risk processes, symptom emergence, and adaptation in ASD that offers a framework for understanding early brain plasticity in ASD and its role in prevention of the disorder.
Lyden, Hannah; Gimbel, Sarah I; Del Piero, Larissa; Tsai, A Bryna; Sachs, Matthew E; Kaplan, Jonas T; Margolin, Gayla; Saxbe, Darby
2016-01-01
Associations between brain structure and early adversity have been inconsistent in the literature. These inconsistencies may be partially due to methodological differences. Different methods of brain segmentation may produce different results, obscuring the relationship between early adversity and brain volume. Moreover, adolescence is a time of significant brain growth and certain brain areas have distinct rates of development, which may compromise the accuracy of automated segmentation approaches. In the current study, 23 adolescents participated in two waves of a longitudinal study. Family aggression was measured when the youths were 12 years old, and structural scans were acquired an average of 4 years later. Bilateral amygdalae and hippocampi were segmented using three different methods (manual tracing, FSL, and NeuroQuant). The segmentation estimates were compared, and linear regressions were run to assess the relationship between early family aggression exposure and all three volume segmentation estimates. Manual tracing results showed a positive relationship between family aggression and right amygdala volume, whereas FSL segmentation showed negative relationships between family aggression and both the left and right hippocampi. However, results indicate poor overlap between methods, and different associations were found between early family aggression exposure and brain volume depending on the segmentation method used.
Lyden, Hannah; Gimbel, Sarah I.; Del Piero, Larissa; Tsai, A. Bryna; Sachs, Matthew E.; Kaplan, Jonas T.; Margolin, Gayla; Saxbe, Darby
2016-01-01
Associations between brain structure and early adversity have been inconsistent in the literature. These inconsistencies may be partially due to methodological differences. Different methods of brain segmentation may produce different results, obscuring the relationship between early adversity and brain volume. Moreover, adolescence is a time of significant brain growth and certain brain areas have distinct rates of development, which may compromise the accuracy of automated segmentation approaches. In the current study, 23 adolescents participated in two waves of a longitudinal study. Family aggression was measured when the youths were 12 years old, and structural scans were acquired an average of 4 years later. Bilateral amygdalae and hippocampi were segmented using three different methods (manual tracing, FSL, and NeuroQuant). The segmentation estimates were compared, and linear regressions were run to assess the relationship between early family aggression exposure and all three volume segmentation estimates. Manual tracing results showed a positive relationship between family aggression and right amygdala volume, whereas FSL segmentation showed negative relationships between family aggression and both the left and right hippocampi. However, results indicate poor overlap between methods, and different associations were found between early family aggression exposure and brain volume depending on the segmentation method used. PMID:27656121
Left Hemisphere Regions Are Critical for Language in the Face of Early Left Focal Brain Injury
ERIC Educational Resources Information Center
Beharelle, Anjali Raja; Dick, Anthony Steven; Josse, Goulven; Solodkin, Ana; Huttenlocher, Peter R.; Levine, Susan C.; Small, Steven L.
2010-01-01
A predominant theory regarding early stroke and its effect on language development, is that early left hemisphere lesions trigger compensatory processes that allow the right hemisphere to assume dominant language functions, and this is thought to underlie the near normal language development observed after early stroke. To test this theory, we…
Nanotheranostics: Emerging Strategies for Early Diagnosis and Therapy of Brain Cancer
Sonali; Viswanadh, Matte Kasi; Singh, Rahul Pratap; Agrawal, Poornima; Mehata, Abhishesh Kumar; Pawde, Datta Maroti; Narendra; Sonkar, Roshan; Muthu, Madaswamy Sona
2018-01-01
Nanotheranostics have demonstrated the development of advanced platforms that can diagnose brain cancer at early stages, initiate first-line therapy, monitor it, and if needed, rapidly start subsequent treatments. In brain nanotheranostics, therapeutic as well as diagnostic entities are loaded in a single nanoplatform, which can be further developed as a clinical formulation for targeting various modes of brain cancer. In the present review, we concerned about theranostic nanosystems established till now in the research field. These include gold nanoparticles, carbon nanotubes, magnetic nanoparticles, mesoporous silica nanoparticles, quantum dots, polymeric nanoparticles, upconversion nanoparticles, polymeric micelles, solid lipid nanoparticles and dendrimers for the advanced detection and treatment of brain cancer with advanced features. Also, we included the role of three-dimensional models of the BBB and cancer stem cell concept for the advanced characterization of nanotheranostic systems for the unification of diagnosis and treatment of brain cancer. In future, brain nanotheranostics will be able to provide personalized treatment which can make brain cancer even remediable or at least treatable at the primary stages. PMID:29291164
Shaping Youngest Minds. Study Guide [and Videotape].
ERIC Educational Resources Information Center
Schrank, Louise Welsh
Noting research indicating that the flow of interaction with infants influences their brain development, this viewer's guide and videotape examine characteristics of early brain development and how parents can positively affect the infant's development in a number of areas. The first part of the viewer's guide provides an overview of the…
Intergenerational neural mediators of early-life anxious temperament.
Fox, Andrew S; Oler, Jonathan A; Shackman, Alexander J; Shelton, Steven E; Raveendran, Muthuswamy; McKay, D Reese; Converse, Alexander K; Alexander, Andrew; Davidson, Richard J; Blangero, John; Rogers, Jeffrey; Kalin, Ned H
2015-07-21
Understanding the heritability of neural systems linked to psychopathology is not sufficient to implicate them as intergenerational neural mediators. By closely examining how individual differences in neural phenotypes and psychopathology cosegregate as they fall through the family tree, we can identify the brain systems that underlie the parent-to-child transmission of psychopathology. Although research has identified genes and neural circuits that contribute to the risk of developing anxiety and depression, the specific neural systems that mediate the inborn risk for these debilitating disorders remain unknown. In a sample of 592 young rhesus monkeys that are part of an extended multigenerational pedigree, we demonstrate that metabolism within a tripartite prefrontal-limbic-midbrain circuit mediates some of the inborn risk for developing anxiety and depression. Importantly, although brain volume is highly heritable early in life, it is brain metabolism-not brain structure-that is the critical intermediary between genetics and the childhood risk to develop stress-related psychopathology.
Early Learning: Birth to Third Grade Continuum. Annotated Bibliography
ERIC Educational Resources Information Center
Hite, Jenny
2014-01-01
Recent studies indicate that persistent achievement gaps among children begin as early as 18 months, years before most publicly funded prekindergarten programs offer enrollment. Early childhood development necessitates more than access to pre-K at age four. Proper brain development requires adequate nutrition, access to quality healthcare, and…
Why Do Children of the Caribbean Need Programmes of Early Childhood Education and Development?
ERIC Educational Resources Information Center
Williams, Sian
This paper examines the needs of young children in the Caribbean region with an emphasis on early childhood development programs in addition to early childhood education. The paper maintains that the first 3 years of life are critical for brain development; parents and caregivers should be enabled to provide appropriate experiences, and children…
ERIC Educational Resources Information Center
Axton, J. H. M.
Factors which influence child development are listed and briefly discussed. These factors are (1) mother's childhood, (2) mother's age, (3) care during pregnancy and delivery, (4) early neonatal factors, (5) birth interval, (6) effect of repeated infection and malnutrition on brain growth and intellectual development, and (7) home environment. The…
ERIC Educational Resources Information Center
Center on the Developing Child at Harvard University, 2007
2007-01-01
This report combines neuroscience, child development research, and program evaluation data to better inform policymakers' decisions about investing in and supporting existing early childhood programs. Core child development concepts highlight the importance of early experiences on the development of brain architecture and, in turn, future…
Dinel, A L; Rey, C; Baudry, C; Fressange-Mazda, C; Le Ruyet, P; Nadjar, A; Pallet, P; Joffre, C; Layé, S
2016-10-01
Polyunsaturated fatty acids (PUFAs) are essential fatty acids, which are critical for brain development and later life cognitive functions. The main brain PUFAs are docosahexaenoic acid (DHA) for the n-3 family and arachidonic acid (ARA) for the n-6 family, which are provided to the post-natal brain by breast milk or infant formula. Recently, the use of dairy lipids (DL) in replacement of vegetable lipids (VL) was revealed to potently promote the accretion of DHA in the developing brain. Brain DHA, in addition to be a key component of brain development, display potent anti-inflammatory activities, which protect the brain from adverse inflammatory events. In this work, we evaluated the protective effect of partial replacement of VL by DL, supplemented or not with DHA and ARA, on post-natal inflammation and its consequence on memory. Mice were fed with diets poor in vegetal n-3 PUFA (Def VL), balanced in vegetal n-3/n-6 PUFA (Bal VL), balanced in dairy lipids (Bal DL) or enriched in DHA and ARA (Supp VL; Supp DL) from the first day of gestation until adulthood. At post-natal day 14 (PND14), pups received a single administration of the endotoxin lipopolysaccharide (LPS) and brain cytokine expression, microglia phenotype and neurogenesis were measured. In a second set of experiments, memory and neurogenesis were measured at adulthood. Overall, our data showed that lipid quality of the diet modulates early life LPS effect on microglia phenotype, brain cytokine expression and neurogenesis at PND14 and memory at adulthood. In particular, Bal DL diet protects from the adverse effect of early life LPS exposure on PND14 neurogenesis and adult spatial memory. Copyright © 2016 Elsevier Ltd. All rights reserved.
Zhang, Chengjin; Boa-Amponsem, Oswald; Cole, Gregory J
2017-08-01
This study was undertaken to ascertain whether defined markers of early zebrafish brain development are affected by chronic ethanol exposure or morpholino knockdown of agrin, sonic hedgehog, retinoic acid, and fibroblast growth factors, four signaling molecules that are suggested to be ethanol sensitive. Zebrafish embryos were exposed to 2% ethanol from 6 to 24 hpf or injected with agrin, shha, aldh1a3, or fgf8a morpholinos. In situ hybridization was employed to analyze otx2, pax6a, epha4a, krx20, pax2a, fgf8a, wnt1, and eng2b expression during early brain development. Our results showed that pax6a mRNA expression was decreased in eye, forebrain, and hindbrain of both chronic ethanol exposed and select MO treatments. Epha4a expression in rhombomere R1 boundary was decreased in chronic ethanol exposure and aldh1a3 morphants, lost in fgf8a morphants, but largely unaffected in agrin and shha morphants. Ectopic pax6a and epha4a expression in midbrain was only found in fgf8a morphants. These results suggest that while chronic ethanol induces obvious morphological change in brain architecture, many molecular markers of these brain structures are relatively unaffected by ethanol exposure.
Stimulation of functional vision in children with perinatal brain damage.
Alimović, Sonja; Mejaski-Bosnjak, Vlatka
2011-01-01
Cerebral visual impairment (CVI) is one of the most common causes of bilateral visual loss, which frequently occurs due to perinatal brain injury. Vision in early life has great impact on acquisition of basic comprehensions which are fundamental for further development. Therefore, early detection of visual problems and early intervention is necessary. The aim of the present study is to determine specific visual functioning of children with perinatal brain damage and the influence of visual stimulation on development of functional vision at early age of life. We initially assessed 30 children with perinatal brain damage up to 3 years of age, who were reffered to our pediatric low vision cabinet in "Little house" from child neurologists, ophthalmologists Type and degree of visual impairment was determined according to functional vision assessment of each child. On the bases of those assessments different kind of visual stimulations were carried out with children who have been identified to have a certain visual impairment. Through visual stimulation program some of the children were stimulated with light stimulus, some with different materials under the ultraviolet (UV) light, and some with bright color and high contrast materials. Children were also involved in program of early stimulation of overall sensory motor development. Goals and methods of therapy were determined individually, based on observation of child's possibilities and need. After one year of program, reassessment was done. Results for visual functions and functional vision were compared to evaluate the improvement of the vision development. These results have shown that there was significant improvement in functional vision, especially in visual attention and visual communication.
Toward Understanding How Early-Life Stress Reprograms Cognitive and Emotional Brain Networks.
Chen, Yuncai; Baram, Tallie Z
2016-01-01
Vulnerability to emotional disorders including depression derives from interactions between genes and environment, especially during sensitive developmental periods. Adverse early-life experiences provoke the release and modify the expression of several stress mediators and neurotransmitters within specific brain regions. The interaction of these mediators with developing neurons and neuronal networks may lead to long-lasting structural and functional alterations associated with cognitive and emotional consequences. Although a vast body of work has linked quantitative and qualitative aspects of stress to adolescent and adult outcomes, a number of questions are unclear. What distinguishes 'normal' from pathologic or toxic stress? How are the effects of stress transformed into structural and functional changes in individual neurons and neuronal networks? Which ones are affected? We review these questions in the context of established and emerging studies. We introduce a novel concept regarding the origin of toxic early-life stress, stating that it may derive from specific patterns of environmental signals, especially those derived from the mother or caretaker. Fragmented and unpredictable patterns of maternal care behaviors induce a profound chronic stress. The aberrant patterns and rhythms of early-life sensory input might also directly and adversely influence the maturation of cognitive and emotional brain circuits, in analogy to visual and auditory brain systems. Thus, unpredictable, stress-provoking early-life experiences may influence adolescent cognitive and emotional outcomes by disrupting the maturation of the underlying brain networks. Comprehensive approaches and multiple levels of analysis are required to probe the protean consequences of early-life adversity on the developing brain. These involve integrated human and animal-model studies, and approaches ranging from in vivo imaging to novel neuroanatomical, molecular, epigenomic, and computational methodologies. Because early-life adversity is a powerful determinant of subsequent vulnerabilities to emotional and cognitive pathologies, understanding the underlying processes will have profound implications for the world's current and future children.
NASA Astrophysics Data System (ADS)
Du, Huiping; Wang, Shu; Wang, Xingfu; Zhu, Xiaoqin; Zhuo, Shuangmu; Chen, Jianxin
2016-10-01
Ischemic stroke is one of the common neurological diseases, and it is becoming the leading causes of death and permanent disability around the world. Early and accurate identification of the potentially salvageable boundary region of ischemia brain tissues may enable selection of the most appropriate candidates for early stroke therapies. In this work, TPEF microscopy was used to image the microstructures of normal brain tissues, ischemia regions and the boundary region between normal and ischemia brain tissues. The ischemia brain tissues from Sprague-Dawley (SD) rats were subjected to 6 hours of middle cerebral artery occlusion (MCAO). Our study demonstrates that TPEF microscopy has the ability to not only reveal the morphological changes of the neurons but also identify the boundary between normal brain tissue and ischemia region, which correspond well to the hematoxylin and eosin (H and E) stained images. With the development of miniaturized TPEF microscope imaging devices, TPEF microscopy can be developed into an effectively diagnostic and monitoring tool for cerebral ischemia.
Leclercq, Sophie; Mian, Firoz M.; Stanisz, Andrew M.; Bindels, Laure B.; Cambier, Emmanuel; Ben-Amram, Hila; Koren, Omry; Forsythe, Paul; Bienenstock, John
2017-01-01
There is increasing concern about potential long-term effects of antibiotics on children's health. Epidemiological studies have revealed that early-life antibiotic exposure can increase the risk of developing immune and metabolic diseases, and rodent studies have shown that administration of high doses of antibiotics has long-term effects on brain neurochemistry and behaviour. Here we investigate whether low-dose penicillin in late pregnancy and early postnatal life induces long-term effects in the offspring of mice. We find that penicillin has lasting effects in both sexes on gut microbiota, increases cytokine expression in frontal cortex, modifies blood–brain barrier integrity and alters behaviour. The antibiotic-treated mice exhibit impaired anxiety-like and social behaviours, and display aggression. Concurrent supplementation with Lactobacillus rhamnosus JB-1 prevents some of these alterations. These results warrant further studies on the potential role of early-life antibiotic use in the development of neuropsychiatric disorders, and the possible attenuation of these by beneficial bacteria. PMID:28375200
Rebooting the Brain: Using Early Childhood Education to Heal Trauma from Abuse and Neglect
ERIC Educational Resources Information Center
McLintock, Ben
2011-01-01
Abused and neglected children live in a world that usually includes some sort of violence, chaos, and tremendous physical and mental stress. This toxic environment wreaks havoc on a child's developing brain. This article discusses how to use early childhood education to heal trauma from abuse and neglect. It shares the story of two children, Bryce…
Brain Development in Autism: Early Overgrowth Followed by Premature Arrest of Growth
ERIC Educational Resources Information Center
Courchesne, Eric
2004-01-01
Due to the relatively late age of clinical diagnosis of autism, the early brain pathology of children with autism has remained largely unstudied. The increased use of retrospective measures such as head circumference, along with a surge of MRI studies of toddlers with autism, have opened a whole new area of research and discovery. Recent studies…
Trajectories of Early Brain Volume Development in Fragile X Syndrome and Autism
ERIC Educational Resources Information Center
Hazlett, Heather Cody; Poe, Michele D.; Lightbody, Amy A.; Styner, Martin; MacFall, James R.; Reiss, Allan L.; Piven, Joseph
2012-01-01
Objective: To examine patterns of early brain growth in young children with fragile X syndrome (FXS) compared with a comparison group (controls) and a group with idiopathic autism. Method: The study included 53 boys 18 to 42 months of age with FXS, 68 boys with idiopathic autism (autism spectrum disorder), and a comparison group of 50 typically…
Development of a brain MRI-based hidden Markov model for dementia recognition.
Chen, Ying; Pham, Tuan D
2013-01-01
Dementia is an age-related cognitive decline which is indicated by an early degeneration of cortical and sub-cortical structures. Characterizing those morphological changes can help to understand the disease development and contribute to disease early prediction and prevention. But modeling that can best capture brain structural variability and can be valid in both disease classification and interpretation is extremely challenging. The current study aimed to establish a computational approach for modeling the magnetic resonance imaging (MRI)-based structural complexity of the brain using the framework of hidden Markov models (HMMs) for dementia recognition. Regularity dimension and semi-variogram were used to extract structural features of the brains, and vector quantization method was applied to convert extracted feature vectors to prototype vectors. The output VQ indices were then utilized to estimate parameters for HMMs. To validate its accuracy and robustness, experiments were carried out on individuals who were characterized as non-demented and mild Alzheimer's diseased. Four HMMs were constructed based on the cohort of non-demented young, middle-aged, elder and demented elder subjects separately. Classification was carried out using a data set including both non-demented and demented individuals with a wide age range. The proposed HMMs have succeeded in recognition of individual who has mild Alzheimer's disease and achieved a better classification accuracy compared to other related works using different classifiers. Results have shown the ability of the proposed modeling for recognition of early dementia. The findings from this research will allow individual classification to support the early diagnosis and prediction of dementia. By using the brain MRI-based HMMs developed in our proposed research, it will be more efficient, robust and can be easily used by clinicians as a computer-aid tool for validating imaging bio-markers for early prediction of dementia.
Environmental Complexity and Central Nervous System Development and Function
ERIC Educational Resources Information Center
Lewis, Mark H.
2004-01-01
Environmental restriction or deprivation early in development can induce social, cognitive, affective, and motor abnormalities similar to those associated with autism. Conversely, rearing animals in larger, more complex environments results in enhanced brain structure and function, including increased brain weight, dendritic branching,…
A Single-Cell Roadmap of Lineage Bifurcation in Human ESC Models of Embryonic Brain Development.
Yao, Zizhen; Mich, John K; Ku, Sherman; Menon, Vilas; Krostag, Anne-Rachel; Martinez, Refugio A; Furchtgott, Leon; Mulholland, Heather; Bort, Susan; Fuqua, Margaret A; Gregor, Ben W; Hodge, Rebecca D; Jayabalu, Anu; May, Ryan C; Melton, Samuel; Nelson, Angelique M; Ngo, N Kiet; Shapovalova, Nadiya V; Shehata, Soraya I; Smith, Michael W; Tait, Leah J; Thompson, Carol L; Thomsen, Elliot R; Ye, Chaoyang; Glass, Ian A; Kaykas, Ajamete; Yao, Shuyuan; Phillips, John W; Grimley, Joshua S; Levi, Boaz P; Wang, Yanling; Ramanathan, Sharad
2017-01-05
During human brain development, multiple signaling pathways generate diverse cell types with varied regional identities. Here, we integrate single-cell RNA sequencing and clonal analyses to reveal lineage trees and molecular signals underlying early forebrain and mid/hindbrain cell differentiation from human embryonic stem cells (hESCs). Clustering single-cell transcriptomic data identified 41 distinct populations of progenitor, neuronal, and non-neural cells across our differentiation time course. Comparisons with primary mouse and human gene expression data demonstrated rostral and caudal progenitor and neuronal identities from early brain development. Bayesian analyses inferred a unified cell-type lineage tree that bifurcates between cortical and mid/hindbrain cell types. Two methods of clonal analyses confirmed these findings and further revealed the importance of Wnt/β-catenin signaling in controlling this lineage decision. Together, these findings provide a rich transcriptome-based lineage map for studying human brain development and modeling developmental disorders. Copyright © 2017 Elsevier Inc. All rights reserved.
Spann, Marisa N; Bansal, Ravi; Rosen, Tove S; Peterson, Bradley S
2014-09-01
Knowledge of the role of brain maturation in the development of cognitive abilities derives primarily from studies of school-age children to adults. Little is known about the morphological features of the neonatal brain that support the subsequent development of abilities in early childhood, when maturation of the brain and these abilities are the most dynamic. The goal of our study was to determine whether brain morphology during the neonatal period supports early cognitive development through 2 years of age. We correlated morphological features of the cerebral surface assessed using deformation-based measures (surface distances) of high-resolution MRI scans for 33 healthy neonates, scanned between the first to sixth week of postmenstrual life, with subsequent measures of their motor, language, and cognitive abilities at ages 6, 12, 18, and 24 months. We found that morphological features of the cerebral surface of the frontal, mesial prefrontal, temporal, and occipital regions correlated with subsequent motor scores, posterior parietal regions correlated with subsequent language scores, and temporal and occipital regions correlated with subsequent cognitive scores. Measures of the anterior and middle portions of the cingulate gyrus correlated with scores across all three domains of ability. Most of the significant findings were inverse correlations located bilaterally in the brain. The inverse correlations may suggest either that a more protracted morphological maturation or smaller local volumes of neonatal brain tissue supports better performance on measures of subsequent motor, language, and cognitive abilities throughout the first 2 years of postnatal life. The correlations of morphological measures of the cingulate with measures of performance across all domains of ability suggest that the cingulate supports a broad range of skills in infancy and early childhood, similar to its functions in older children and adults. Copyright © 2014 Wiley Periodicals, Inc.
A Matter of Timing: Enhancing Positive Change for the Developing Brain
ERIC Educational Resources Information Center
Fox, Nathan A.; Zeanah, Charles H.; Nelson, Charles A.
2014-01-01
Neuroscientists have long believed that there are sensitive periods in development during which the effects of experience play a critical role. And developmental psychologists have argued for the importance of early experience in the first years of life as being critical for brain and behavioral development. Most of the neuroscience research…
4D MEMRI atlas of neonatal FVB/N mouse brain development.
Szulc, Kamila U; Lerch, Jason P; Nieman, Brian J; Bartelle, Benjamin B; Friedel, Miriam; Suero-Abreu, Giselle A; Watson, Charles; Joyner, Alexandra L; Turnbull, Daniel H
2015-09-01
The widespread use of the mouse as a model system to study brain development has created the need for noninvasive neuroimaging methods that can be applied to early postnatal mice. The goal of this study was to optimize in vivo three- (3D) and four-dimensional (4D) manganese (Mn)-enhanced MRI (MEMRI) approaches for acquiring and analyzing data from the developing mouse brain. The combination of custom, stage-dependent holders and self-gated (motion-correcting) 3D MRI sequences enabled the acquisition of high-resolution (100-μm isotropic), motion artifact-free brain images with a high level of contrast due to Mn-enhancement of numerous brain regions and nuclei. We acquired high-quality longitudinal brain images from two groups of FVB/N strain mice, six mice per group, each mouse imaged on alternate odd or even days (6 3D MEMRI images at each day) covering the developmental stages between postnatal days 1 to 11. The effects of Mn-exposure, anesthesia and MRI were assessed, showing small but significant transient effects on body weight and brain volume, which recovered with time and did not result in significant morphological differences when compared to controls. Metrics derived from deformation-based morphometry (DBM) were used for quantitative analysis of changes in volume and position of a number of brain regions. The cerebellum, a brain region undergoing significant changes in size and patterning at early postnatal stages, was analyzed in detail to demonstrate the spatiotemporal characterization made possible by this new atlas of mouse brain development. These results show that MEMRI is a powerful tool for quantitative analysis of mouse brain development, with great potential for in vivo phenotype analysis in mouse models of neurodevelopmental diseases. Copyright © 2015 Elsevier Inc. All rights reserved.
Wang, Rongpin; Wilkinson, Molly; Kane, Tara; Takahashi, Emi
2017-01-01
There has been evidence that during brain development, emerging thalamocortical (TC) and corticothalamic (CT) pathways converge in some brain regions and follow each other's trajectories to their final destinations. Corpus callosal (CC) pathways also emerge at a similar developmental stage, and are known to converge with TC pathways in specific cortical regions in mature brains. Given the functional relationships between TC and CC pathways, anatomical convergence of the two pathways are likely important for their functional integration. However, it is unknown (1) where TC and CT subcortically converge in the human brain, and (2) where TC and CC converge in the cortex of the human brain, due to the limitations of non-invasive methods. The goals of this study were to describe the spatio-temporal relationships in the development of the TC/CT and CC pathways in the human brain, using high-angular resolution diffusion MR imaging (HARDI) tractography. Emerging cortical, TC and CC pathways were identified in postmortem fetal brains ranging from 17 gestational weeks (GW) to 30 GW, as well as in vivo 34-40 GW newborns. Some pathways from the thalami were found to be converged with pathways from the cerebral cortex as early as 17 GW. Such convergence was observed mainly in anterior and middle regions of the brain until 21 GW. At 22 GW and onwards, posterior pathways from the thalami also converged with cortical pathways. Many CC pathways reached the full length up to the cortical surface as early as 17 GW, while pathways linked to thalami (not only TC axons but also including pathways linked to thalamic neuronal migration) reached the cortical surface at and after 20 GW. These results suggest that CC pathways developed earlier than the TC pathways. The two pathways were widespread at early stages, but by 40 GW they condensed and formed groups of pathways that projected to specific regions of the cortex and overlapped in some brain regions. These results suggest that HARDI tractography has the potential to identify developing TC/CT and CC pathways with the timing and location of their convergence in fetal stages persisting in postnatal development.
Wang, Rongpin; Wilkinson, Molly; Kane, Tara; Takahashi, Emi
2017-01-01
There has been evidence that during brain development, emerging thalamocortical (TC) and corticothalamic (CT) pathways converge in some brain regions and follow each other's trajectories to their final destinations. Corpus callosal (CC) pathways also emerge at a similar developmental stage, and are known to converge with TC pathways in specific cortical regions in mature brains. Given the functional relationships between TC and CC pathways, anatomical convergence of the two pathways are likely important for their functional integration. However, it is unknown (1) where TC and CT subcortically converge in the human brain, and (2) where TC and CC converge in the cortex of the human brain, due to the limitations of non-invasive methods. The goals of this study were to describe the spatio-temporal relationships in the development of the TC/CT and CC pathways in the human brain, using high-angular resolution diffusion MR imaging (HARDI) tractography. Emerging cortical, TC and CC pathways were identified in postmortem fetal brains ranging from 17 gestational weeks (GW) to 30 GW, as well as in vivo 34–40 GW newborns. Some pathways from the thalami were found to be converged with pathways from the cerebral cortex as early as 17 GW. Such convergence was observed mainly in anterior and middle regions of the brain until 21 GW. At 22 GW and onwards, posterior pathways from the thalami also converged with cortical pathways. Many CC pathways reached the full length up to the cortical surface as early as 17 GW, while pathways linked to thalami (not only TC axons but also including pathways linked to thalamic neuronal migration) reached the cortical surface at and after 20 GW. These results suggest that CC pathways developed earlier than the TC pathways. The two pathways were widespread at early stages, but by 40 GW they condensed and formed groups of pathways that projected to specific regions of the cortex and overlapped in some brain regions. These results suggest that HARDI tractography has the potential to identify developing TC/CT and CC pathways with the timing and location of their convergence in fetal stages persisting in postnatal development. PMID:29163000
Demystifying the Adolescent Brain
ERIC Educational Resources Information Center
Steinberg, Laurence
2011-01-01
Understanding the nature of brain development in adolescence helps explain why adolescents can vacillate so often between mature and immature behavior. Early and middle adolescence, in particular, are times of heightened vulnerability to risky and reckless behavior because the brain's reward center is easily aroused, but the systems that control…
Ugajin, Atsushi; Watanabe, Takayuki; Uchiyama, Hironobu; Sasaki, Tetsuhiko; Yajima, Shunsuke; Ono, Masato
2016-09-16
Specific genes quickly transcribed after extracellular stimuli without de novo protein synthesis are known as immediate early genes (IEGs) and are thought to contribute to learning and memory processes in the mature nervous system of vertebrates. A recent study revealed that the homolog of Early growth response protein-1 (Egr-1), which is one of the best-characterized vertebrate IEGs, shared similar properties as a neural activity-dependent gene in the adult brain of insects. With regard to the roles of vertebrate Egr-1 in neural development, the contribution to the development and growth of visual systems has been reported. However, in insects, the expression dynamics of the Egr-1 homologous gene during neural development remains poorly understood. Our expression analysis demonstrated that AmEgr, a honeybee homolog of Egr-1, was transiently upregulated in the developing brain during the early to mid pupal stages. In situ hybridization and 5-bromo-2'-deoxyuridine (BrdU) immunohistochemistry revealed that AmEgr was mainly expressed in post-mitotic cells in optic lobes, the primary visual center of the insect brain. These findings suggest the evolutionarily conserved role of Egr homologs in the development of visual systems in vertebrates and insects. Copyright © 2016 Elsevier Inc. All rights reserved.
Premature brain aging in humans exposed to maternal nutrient restriction during early gestation.
Franke, Katja; Gaser, Christian; Roseboom, Tessa J; Schwab, Matthias; de Rooij, Susanne R
2018-06-01
Prenatal exposure to undernutrition is widespread in both developing and industrialized countries, causing irreversible damage to the developing brain, resulting in altered brain structure and decreased cognitive function during adulthood. The Dutch famine in 1944/45 was a humanitarian disaster, now enabling studies of the effects of prenatal undernutrition during gestation on brain aging in late adulthood. We hypothesized that study participants prenatally exposed to maternal nutrient restriction (MNR) would demonstrate altered brain structure resembling premature brain aging in late adulthood, expecting the effect being stronger in men. Utilizing the Dutch famine birth cohort (n = 118; mean age: 67.5 ± 0.9 years), this study implements an innovative biomarker for individual brain aging, using structural neuroimaging. BrainAGE was calculated using state-of-the-art pattern recognition methods, trained on an independent healthy reference sample, then applied to the Dutch famine MRI sample, to evaluate the effects of prenatal undernutrition during early gestation on individual brain aging in late adulthood. Exposure to famine in early gestation was associated with BrainAGE scores indicative of an older-appearing brain in the male sample (mean difference to subjects born before famine: 4.3 years, p < 0.05). Furthermore, in explaining the observed variance in individual BrainAGE scores in the male sample, maternal age at birth, head circumference at birth, medical treatment of hypertension, history of cerebral incidences, actual heart rate, and current alcohol intake emerged to be the most influential variables (adjusted R 2 = 0.63, p < 0.01). The findings of our study on exposure to prenatal undernutrition being associated with a status of premature brain aging during late adulthood, as well as individual brain structure being shaped by birth- and late-life health characteristics, are strongly supporting the critical importance of sufficient nutrient supply during pregnancy. Interestingly, the status of premature brain aging in participants exposed to the Dutch famine during early gestation occurred in the absence of fetal growth restriction at birth as well as vascular pathology in late-life. Additionally, the neuroimaging brain aging biomarker presented in this study will further enable tracking effects of environmental influences or (preventive) treatments on individual brain maturation and aging in epidemiological and clinical studies. Copyright © 2017 Elsevier Inc. All rights reserved.
Garza-Lombó, Carla; Gonsebatt, María E.
2016-01-01
The kinase mammalian target of rapamycin (mTOR) integrates signals triggered by energy, stress, oxygen levels, and growth factors. It regulates ribosome biogenesis, mRNA translation, nutrient metabolism, and autophagy. mTOR participates in various functions of the brain, such as synaptic plasticity, adult neurogenesis, memory, and learning. mTOR is present during early neural development and participates in axon and dendrite development, neuron differentiation, and gliogenesis, among other processes. Furthermore, mTOR has been shown to modulate lifespan in multiple organisms. This protein is an important energy sensor that is present throughout our lifetime its role must be precisely described in order to develop therapeutic strategies and prevent diseases of the central nervous system. The aim of this review is to present our current understanding of the functions of mTOR in neural development, the adult brain and aging. PMID:27378854
The EPA must evaluate the risk of exposure of the developing brain to chemicals with the potential to disrupt thyroid hormone homeostasis. The existing literature identifies morphological and neurochemical indices of severe neonatal hypothyroidism in the early postnatal period i...
Wang, Yang; Fang, Jian; Nie, Jun; Dai, Ling; Hu, Weiheng; Zhang, Jie; Ma, Xiangjuan; Han, Jindi; Chen, Xiaoling; Tian, Guangming; Wu, Di; Han, Sen; Long, Jieran
2016-08-20
Radiotherapy combined with chemotherapy or molecular targeted therapy remains the standard of treatment for brain metastases from non-small cell lung cancer (NSCLC). The aim of this study is to determine if the deferral of brain radiotherapy impacts patient outcomes. Between May 2003 and December 2015, a total of 198 patients with brain metastases from NSCLC who received both brain radiotherapy and systemic therapy (chemotherapy or targeted therapy) were identified. The rate of grade 3-4 adverse reactions related to chemotherapy and radiotherapy had no significant difference between two groups. 127 patients received concurrent brain radiotherapy and systemic therapy, and 71 patients received deferred brain radiotherapy after at least two cycles of chemotherapy or targeted therapy. Disease specific-graded prognostic assessment was similar in early radiotherapy group and deferred radiotherapy group. Median overall survival (OS) was longer in early radiotherapy group compared to deferred radiotherapy group (17.9 months vs 12.6 months; P=0.038). Progression free survival (PFS) was also improved in patients receiving early radiotherapy compared to those receiving deferred radiotherapy (4.0 months vs 3.0 months; P<0.01). Receiving tyrosine kinase inhibitor (TKI) therapy after the diagnosis of brain metastases as any line therapy improved the OS (20.0 months vs 10.7 months; P<0.01), whereas receiving TKI as first line therapy did not (17.9 months vs 15.2 months; P=0.289). Our study suggests that the use of deferred brain radiotherapy may resulted in inferior OS in patients with NSCLC who develop brain metastases. A prospective multi-central randomized study is imminently needed.
The effects of vitamin D on brain development and adult brain function.
Kesby, James P; Eyles, Darryl W; Burne, Thomas H J; McGrath, John J
2011-12-05
A role for vitamin D in brain development and function has been gaining support over the last decade. Multiple lines of evidence suggest that this vitamin is actually a neuroactive steroid that acts on brain development, leading to alterations in brain neurochemistry and adult brain function. Early deficiencies have been linked with neuropsychiatric disorders, such as schizophrenia, and adult deficiencies have been associated with a host of adverse brain outcomes, including Parkinson's disease, Alzheimer's disease, depression and cognitive decline. This review summarises the current state of research on the actions of vitamin D in the brain and the consequences of deficiencies in this vitamin. Furthermore, we discuss specific implications of vitamin D status on the neurotransmitter, dopamine. Copyright © 2011 Elsevier Ltd. All rights reserved.
Genetics Home Reference: acrocallosal syndrome
... callosum occurs when the tissue that connects the left and right halves of the brain (the corpus callosum ) fails to form normally during the early stages of development before birth. Other brain abnormalities, including the growth ...
Fumagalli, Monica; Provenzi, Livio; De Carli, Pietro; Dessimone, Francesca; Sirgiovanni, Ida; Giorda, Roberto; Cinnante, Claudia; Squarcina, Letizia; Pozzoli, Uberto; Triulzi, Fabio; Brambilla, Paolo; Borgatti, Renato; Mosca, Fabio; Montirosso, Rosario
2018-01-01
Very preterm (VPT) infants admitted to Neonatal Intensive Care Unit (NICU) are at risk for altered brain growth and less-than-optimal socio-emotional development. Recent research suggests that early NICU-related stress contributes to socio-emotional impairments in VPT infants at 3 months through epigenetic regulation (i.e., DNA methylation) of the serotonin transporter gene (SLC6A4). In the present longitudinal study we assessed: (a) the effects of NICU-related stress and SLC6A4 methylation variations from birth to discharge on brain development at term equivalent age (TEA); (b) the association between brain volume at TEA and socio-emotional development (i.e., Personal-Social scale of Griffith Mental Development Scales, GMDS) at 12 months corrected age (CA). Twenty-four infants had complete data at 12-month-age. SLC6A4 methylation was measured at a specific CpG previously associated with NICU-related stress and socio-emotional stress. Findings confirmed that higher NICU-related stress associated with greater increase of SLC6A4 methylation at NICU discharge. Moreover, higher SLC6A4 discharge methylation was associated with reduced anterior temporal lobe (ATL) volume at TEA, which in turn was significantly associated with less-than-optimal GMDS Personal-Social scale score at 12 months CA. The reduced ATL volume at TEA mediated the pathway linking stress-related increase in SLC6A4 methylation at NICU discharge and socio-emotional development at 12 months CA. These findings suggest that early adversity-related epigenetic changes might contribute to the long-lasting programming of socio-emotional development in VPT infants through epigenetic regulation and structural modifications of the developing brain.
Left hemisphere regions are critical for language in the face of early left focal brain injury.
Raja Beharelle, Anjali; Dick, Anthony Steven; Josse, Goulven; Solodkin, Ana; Huttenlocher, Peter R; Levine, Susan C; Small, Steven L
2010-06-01
A predominant theory regarding early stroke and its effect on language development, is that early left hemisphere lesions trigger compensatory processes that allow the right hemisphere to assume dominant language functions, and this is thought to underlie the near normal language development observed after early stroke. To test this theory, we used functional magnetic resonance imaging to examine brain activity during category fluency in participants who had sustained pre- or perinatal left hemisphere stroke (n = 25) and in neurologically normal siblings (n = 27). In typically developing children, performance of a category fluency task elicits strong involvement of left frontal and lateral temporal regions and a lesser involvement of right hemisphere structures. In our cohort of atypically developing participants with early stroke, expressive and receptive language skills correlated with activity in the same left inferior frontal regions that support language processing in neurologically normal children. This was true independent of either the amount of brain injury or the extent that the injury was located in classical cortical language processing areas. Participants with bilateral activation in left and right superior temporal-inferior parietal regions had better language function than those with either predominantly left- or right-sided unilateral activation. The advantage conferred by left inferior frontal and bilateral temporal involvement demonstrated in our study supports a strong predisposition for typical neural language organization, despite an intervening injury, and argues against models suggesting that the right hemisphere fully accommodates language function following early injury.
Addressing Literacy through Neuroscience
ERIC Educational Resources Information Center
Miller, Steve; Tallal, Paula A.
2006-01-01
Brain is the source of all human thoughts, feelings and emotions. Now the mysteries of the human brain are rapidly being elucidated by neuroscience research. For more than 150 years, neuroscience has held that most of the brain's functionality develops during critical periods in early childhood and that once past these critical periods, the window…
USDA-ARS?s Scientific Manuscript database
Lutein, a dietary carotenoid, selectively accumulates in human retina and brain. While many epidemiological studies show evidence of a relationship between lutein status and cognitive health, lutein's selective uptake in human brain tissue and its potential function in early neural development and c...
ERIC Educational Resources Information Center
Reilly, Judy; Losh, Molly; Bellugi, Ursula; Wulfeck, Beverly
2004-01-01
In this cross-population study, we use narratives as a context to investigate language development in children from 4 to 12 years of age from three experimental groups: children with early unilateral focal brain damage (FL; N=52); children with specific language impairment (SLI; N=44); children with Williams syndrome (WMS; N=36), and typically…
Brain development during the preschool years
Brown, Timothy T.; Jernigan, Terry L.
2012-01-01
The preschool years represent a time of expansive psychological growth, with the initial expression of many psychological abilities that will continue to be refined into young adulthood. Likewise, brain development during this age is characterized by its “blossoming” nature, showing some of its most dynamic and elaborative anatomical and physiological changes. In this article, we review human brain development during the preschool years, sampling scientific evidence from a variety of sources. First, we cover neurobiological foundations of early postnatal development, explaining some of the primary mechanisms seen at a larger scale within neuroimaging studies. Next, we review evidence from both structural and functional imaging studies, which now accounts for a large portion of our current understanding of typical brain development. Within anatomical imaging, we focus on studies of developing brain morphology and tissue properties, including diffusivity of white matter fiber tracts. We also present new data on changes during the preschool years in cortical area, thickness, and volume. Physiological brain development is then reviewed, touching on influential results from several different functional imaging and recording modalities in the preschool and early school-age years, including positron emission tomography (PET), electroencephalography (EEG) and event-related potentials (ERP), functional magnetic resonance imaging (fMRI), magnetoencephalography (MEG), and near-infrared spectroscopy (NIRS). Here, more space is devoted to explaining some of the key methodological factors that are required for interpretation. We end with a section on multimodal and multidimensional imaging approaches, which we believe will be critical for increasing our understanding of brain development and its relationship to cognitive and behavioral growth in the preschool years and beyond. PMID:23007644
Thompson, Deanne K; Kelly, Claire E; Chen, Jian; Beare, Richard; Alexander, Bonnie; Seal, Marc L; Lee, Katherine; Matthews, Lillian G; Anderson, Peter J; Doyle, Lex W; Spittle, Alicia J; Cheong, Jeanie L Y
2018-04-13
It is well established that preterm infants have altered brain development compared with full-term (FT; ≥37 weeks' gestational age [GA]) infants, however the perinatal factors associated with brain development in preterm infants have not been fully elucidated. In particular, perinatal predictors of brain development may differ between very preterm infants (VP; <32 weeks' GA) and infants born moderate (MP; 32-33 weeks' GA) and late (LP; 34-36 weeks' GA) preterm, but this has not been studied. This study aimed to investigate the effects of early life predictors on brain volume and microstructure at term-equivalent age (TEA; 38-44 weeks), and whether these effects differ for GA groups (VP, MP, LP or FT). Structural images from 328 infants (91 VP, 63 MP, 104 LP and 70 FT) were segmented into white matter, cortical grey matter, cerebrospinal fluid, subcortical grey matter, brainstem and cerebellum. Cortical grey matter and white matter images were analysed using voxel-based morphometry. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) images from 361 infants (92 VP, 69 MP, 120 LP and 80 FT) were analysed using Tract-Based Spatial Statistics. Relationships between early life predictors (birthweight standard deviation score [BWSDS], multiple birth, sex, postnatal growth and social risk) and global brain volumes were analysed using linear regressions. Relationships between early life predictors and regional brain volumes and diffusion measures were analysed using voxelwise non-parametric permutation testing. Male sex was associated with higher global volumes of all tissues and higher regional volumes throughout much of the cortical grey matter and white matter, particularly in the FT group. Male sex was also associated with lower FA and higher AD, RD and MD in the optic radiation, external and internal capsules and corona radiata, and these associations were generally similar between GA groups. Higher BWSDS was associated with higher global volumes of all tissues and higher regional volumes in much of the cortical grey matter and white matter in all GA groups, as well as higher FA and lower RD and MD in many major tracts (corpus callosum, optic radiation, internal and external capsules and corona radiata), particularly in the MP and LP groups. Multiple birth and social risk also showed associations with global and regional volumes and regional diffusion values which varied by GA group, but these associations were not independent of the other early life predictors. Postnatal growth was not associated with brain volumes or diffusion values. Early life predictors of brain volumes and microstructure at TEA include sex, BWSDS, multiple birth and social risk, which have different effects based on GA group at birth. This study improves knowledge of the perinatal factors associated with brain abnormalities in infants born across the prematurity spectrum. Copyright © 2018. Published by Elsevier Inc.
Raja Beharelle, Anjali; Griffa, Alessandra; Hagmann, Patric; Solodkin, Ana; McIntosh, Anthony R.; Small, Steven L.; Deco, Gustavo
2015-01-01
Children who sustain a prenatal or perinatal brain injury in the form of a stroke develop remarkably normal cognitive functions in certain areas, with a particular strength in language skills. A dominant explanation for this is that brain regions from the contralesional hemisphere “take over” their functions, whereas the damaged areas and other ipsilesional regions play much less of a role. However, it is difficult to tease apart whether changes in neural activity after early brain injury are due to damage caused by the lesion or by processes related to postinjury reorganization. We sought to differentiate between these two causes by investigating the functional connectivity (FC) of brain areas during the resting state in human children with early brain injury using a computational model. We simulated a large-scale network consisting of realistic models of local brain areas coupled through anatomical connectivity information of healthy and injured participants. We then compared the resulting simulated FC values of healthy and injured participants with the empirical ones. We found that the empirical connectivity values, especially of the damaged areas, correlated better with simulated values of a healthy brain than those of an injured brain. This result indicates that the structural damage caused by an early brain injury is unlikely to have an adverse and sustained impact on the functional connections, albeit during the resting state, of damaged areas. Therefore, these areas could continue to play a role in the development of near-normal function in certain domains such as language in these children. PMID:26063923
Resting-State Functional Connectivity in the Infant Brain: Methods, Pitfalls, and Potentiality.
Mongerson, Chandler R L; Jennings, Russell W; Borsook, David; Becerra, Lino; Bajic, Dusica
2017-01-01
Early brain development is characterized by rapid growth and perpetual reconfiguration, driven by a dynamic milieu of heterogeneous processes. Postnatal brain plasticity is associated with increased vulnerability to environmental stimuli. However, little is known regarding the ontogeny and temporal manifestations of inter- and intra-regional functional connectivity that comprise functional brain networks. Resting-state functional magnetic resonance imaging (rs-fMRI) has emerged as a promising non-invasive neuroinvestigative tool, measuring spontaneous fluctuations in blood oxygen level dependent (BOLD) signal at rest that reflect baseline neuronal activity. Over the past decade, its application has expanded to infant populations providing unprecedented insight into functional organization of the developing brain, as well as early biomarkers of abnormal states. However, many methodological issues of rs-fMRI analysis need to be resolved prior to standardization of the technique to infant populations. As a primary goal, this methodological manuscript will (1) present a robust methodological protocol to extract and assess resting-state networks in early infancy using independent component analysis (ICA), such that investigators without previous knowledge in the field can implement the analysis and reliably obtain viable results consistent with previous literature; (2) review the current methodological challenges and ethical considerations associated with emerging field of infant rs-fMRI analysis; and (3) discuss the significance of rs-fMRI application in infants for future investigations of neurodevelopment in the context of early life stressors and pathological processes. The overarching goal is to catalyze efforts toward development of robust, infant-specific acquisition, and preprocessing pipelines, as well as promote greater transparency by researchers regarding methods used.
Resting-State Functional Connectivity in the Infant Brain: Methods, Pitfalls, and Potentiality
Mongerson, Chandler R. L.; Jennings, Russell W.; Borsook, David; Becerra, Lino; Bajic, Dusica
2017-01-01
Early brain development is characterized by rapid growth and perpetual reconfiguration, driven by a dynamic milieu of heterogeneous processes. Postnatal brain plasticity is associated with increased vulnerability to environmental stimuli. However, little is known regarding the ontogeny and temporal manifestations of inter- and intra-regional functional connectivity that comprise functional brain networks. Resting-state functional magnetic resonance imaging (rs-fMRI) has emerged as a promising non-invasive neuroinvestigative tool, measuring spontaneous fluctuations in blood oxygen level dependent (BOLD) signal at rest that reflect baseline neuronal activity. Over the past decade, its application has expanded to infant populations providing unprecedented insight into functional organization of the developing brain, as well as early biomarkers of abnormal states. However, many methodological issues of rs-fMRI analysis need to be resolved prior to standardization of the technique to infant populations. As a primary goal, this methodological manuscript will (1) present a robust methodological protocol to extract and assess resting-state networks in early infancy using independent component analysis (ICA), such that investigators without previous knowledge in the field can implement the analysis and reliably obtain viable results consistent with previous literature; (2) review the current methodological challenges and ethical considerations associated with emerging field of infant rs-fMRI analysis; and (3) discuss the significance of rs-fMRI application in infants for future investigations of neurodevelopment in the context of early life stressors and pathological processes. The overarching goal is to catalyze efforts toward development of robust, infant-specific acquisition, and preprocessing pipelines, as well as promote greater transparency by researchers regarding methods used. PMID:28856131
Li, Rong; Zhang, Kui; Siegal, Gene P; Wei, Shi
2017-06-01
Brain metastasis from breast cancer generally represents a catastrophic event yet demonstrates substantial biological heterogeneity. There have been limited studies solely focusing on the prognosis of patients with such metastasis. In this study, we carried out a comprehensive analysis in 108 consecutive patients with breast cancer brain metastases between 1997 and 2012 to further define clinicopathological factors associated with early onset of brain metastasis and survival outcomes after development of them. We found that lobular carcinoma, higher clinical stages at diagnosis, and lack of coexisting bone metastasis were significantly associated with a worse brain relapse-free survival when compared with brain-only metastasis. High histologic grade, triple-negative breast cancer, and absence of visceral involvement were unfavorable prognostic factors after brain metastasis. Furthermore, high histologic grade, advanced tumor stages, and lack of coexisting bone involvement indicated a worse overall survival. Thus, the previously established prognostic factors in early stage or advanced breast cancers may not entirely apply to patients with brain metastases. Furthermore, the prognostic significance of the clinicopathological factors differed before and after a patient develops brain metastasis. This knowledge might help in establishing an algorithm to further stratify patients with breast cancer into prognostically significant categories for optimal prevention, screening, and treatment of their brain metastasis. Copyright © 2017 Elsevier Inc. All rights reserved.
Toward a conceptual framework for early brain and behavior development in autism
Piven, J; Elison, J T; Zylka, M J
2017-01-01
Studies of infant siblings of older autistic probands, who are at elevated risk for autism, have demonstrated that the defining features of autism are not present in the first year of life but emerge late in the first and into the second year. A recent longitudinal neuroimaging study of high-risk siblings revealed a specific pattern of brain development in infants later diagnosed with autism, characterized by cortical surface area hyper-expansion in the first year followed by brain volume overgrowth in the second year that is associated with the emergence of autistic social deficits. Together with new observations from genetically defined autism risk alleles and rodent model, these findings suggest a conceptual framework for the early, post-natal development of autism. This framework postulates that an increase in the proliferation of neural progenitor cells and hyper-expansion of cortical surface area in the first year, occurring during a pre-symptomatic period characterized by disrupted sensorimotor and attentional experience, leads to altered experience-dependent neuronal development and decreased elimination of neuronal processes. This process is linked to brain volume overgrowth and disruption of the refinement of neural circuit connections and is associated with the emergence of autistic social deficits in the second year of life. A better understanding of the timing of developmental brain and behavior mechanisms in autism during infancy, a period which precedes the emergence of the defining features of this disorder, will likely have important implications for designing rational approaches to early intervention. PMID:28937691
Prolonged maternal separation disturbs the serotonergic system during early brain development.
Ohta, Ken-Ichi; Miki, Takanori; Warita, Katsuhiko; Suzuki, Shingo; Kusaka, Takashi; Yakura, Tomiko; Liu, Jun-Qian; Tamai, Motoki; Takeuchi, Yoshiki
2014-04-01
Early life stress interrupts brain development through the disturbance of various neurotransmitter and neurotrophic factor activities, but the details remain unclear. In the current study, we focused on the serotonergic system, which plays a critical role in brain development, and examined the time-dependent influence of prolonged maternal separation on male Sprague-Dawley rats. The rats were separated from their dams for 3h twice-daily during postnatal days (PDs) 2-20. The influence of prolonged maternal separation was analyzed on PDs 7, 14, 21, and 28 using HPLC to assess concentrations of serotonin and 5-hydroxyindoleacetic acid and using real-time RT-PCR to measure mRNA expression of the serotonin 1A and 2A receptors in various brain regions. HPLC revealed imbalance between serotonin and 5-hydroxyindoleacetic acid in midbrain raphe nuclei, the amygdala, the hippocampus, and the medial prefrontal cortex (mPFC) on PDs 7 and 14. Furthermore, real-time RT-PCR showed attenuation of mRNA expression of the serotonin 1A receptor in the hippocampus and the mPFC and of the serotonin 2A receptor only in the mPFC on PDs 7 and 14. The observed alterations returned to control levels after maternal separation ended. These findings suggest that the early life stress of prolonged maternal separation disturbs the serotonergic system during a crucial period of brain development, which might in part be responsible for emotional abnormalities later in life. Copyright © 2013 ISDN. Published by Elsevier Ltd. All rights reserved.
Early Life Experience and Gut Microbiome: The Brain-Gut-Microbiota Signaling System.
Cong, Xiaomei; Henderson, Wendy A; Graf, Joerg; McGrath, Jacqueline M
2015-10-01
Over the past decades, advances in neonatal care have led to substantial increases in survival among preterm infants. With these gains, recent concerns have focused on increases in neurodevelopment morbidity related to the interplay between stressful early life experiences and the immature neuroimmune systems. This interplay between these complex mechanisms is often described as the brain-gut signaling system. The role of the gut microbiome and the brain-gut signaling system have been found to be remarkably related to both short- and long-term stress and health. Recent evidence supports that microbial species, ligands, and/or products within the developing intestine play a key role in early programming of the central nervous system and regulation of the intestinal innate immunity. The purpose of this state-of-the-science review is to explore the supporting evidence demonstrating the importance of the brain-gut-microbiota axis in regulation of early life experience. We also discuss the role of gut microbiome in modulating stress and pain responses in high-risk infants. A conceptual framework has been developed to illustrate the regulation mechanisms involved in early life experience. The science in this area is just beginning to be uncovered; having a fundamental understanding of these relationships will be important as new discoveries continue to change our thinking, leading potentially to changes in practice and targeted interventions.
[The impact of malnutrition on brain development, intelligence and school work performance].
Leiva Plaza, B; Inzunza Brito, N; Pérez Torrejón, H; Castro Gloor, V; Jansana Medina, J M; Toro Díaz, T; Almagiá Flores, A; Navarro Díaz, A; Urrutia Cáceres, M S; Cervilla Oltremari, J; Ivanovic Marincovich, D
2001-03-01
The findings from several authors confirm that undernutrition at an early age affects brain growth and intellectual quotient. Most part of students with the lowest scholastic achievement scores present suboptimal head circumference (anthropometric indicator of past nutrition and brain development) and brain size. On the other hand, intellectual quotient measured through intelligence tests (Weschler-R, or the Raven Progressives Matrices Test) has been described positively and significantly correlated with brain size measured by magnetic resonance imaging (MRI); in this respect, intellectual ability has been recognized as one of the best predictors of scholastic achievement. Considering that education is the change lever for the improvement of the quality of life and that the absolute numbers of undernourished children have been increasing in the world, is of major relevance to analyse the long-term effects of undernutrition at an early age. The investigations related to the interrelationships between nutritional status, brain development, intelligence and scholastic achievement are of greatest importance, since nutritional problems affect the lowest socioeconomic stratum with negative consequences manifested in school-age, in higher levels of school dropout, learning problems and a low percentage of students enrolling into higher education. This limits the development of people by which a clear economic benefit to increase adult productivity for government policies might be successful preventing childhood malnutrition.
Clinton, Sarah M.; Glover, Matthew E.; Maltare, Astha; Laszczyk, Ann M.; Mehi, Stephen J.; Simmons, Rebecca K.; King, Gwendalyn D.
2013-01-01
Without the age-regulating protein klotho, mouse lifespan is shortened and the rapid onset of age-related disorders occurs. Conversely, overexpression of klotho extends mouse lifespan. Klotho is most abundant in kidney and expressed in a limited number of other organs, including the brain, where klotho levels are highest in choroid plexus. Reports vary on where klotho is expressed within the brain parenchyma, and no data is available as to whether klotho levels change across postnatal development. We used in situ hybridization to map klotho mRNA expression in the developing and adult rat brain and report moderate, widespread expression across grey matter regions. mRNA expression levels in cortex, hippocampus, caudate putamen, and amygdala decreased during the second week of life and then gradually rose to adult levels by postnatal day 21. Immunohistochemistry revealed a protein expression pattern similar to the mRNA results, with klotho protein expressed widely throughout the brain. Klotho protein co-localized with both the neuronal marker NeuN, as well as, oligodendrocyte marker olig2. These results provide the first anatomical localization of klotho mRNA and protein in rat brain parenchyma and demonstrate that klotho levels vary during early postnatal development. PMID:23838326
ERIC Educational Resources Information Center
Pelphrey, Kevin A.; Shultz, Sarah; Hudac, Caitlin M.; Vander Wyk, Brent C.
2011-01-01
The expression of autism spectrum disorder (ASD) is highly heterogeneous, owing to the complex interactions between genes, the brain, and behavior throughout development. Here we present a model of ASD that implicates an early and initial failure to develop the specialized functions of one or more of the set of neuroanatomical structures involved…
ERIC Educational Resources Information Center
Haydar, Tarik F.
2005-01-01
Studies on human patients and animal models of disease have shown that disruptions in prenatal and early postnatal brain development are a root cause of mental retardation. Since proper brain development is achieved by a strict spatiotemporal control of neurogenesis, cell migration, and patterning of synapses, abnormalities in one or more of these…
ERIC Educational Resources Information Center
Demir, Ozlem Ece; Levine, Susan C.; Goldin-Meadow, Susan
2010-01-01
Children with pre- or perinatal brain injury (PL) exhibit marked plasticity for language learning. Previous work has focused mostly on the emergence of earlier-developing skills, such as vocabulary and syntax. Here we ask whether this plasticity for earlier-developing aspects of language extends to more complex, later-developing language functions…
The Science of Early Childhood Development: Closing the Gap between What We Know and What We Do
ERIC Educational Resources Information Center
National Scientific Council on the Developing Child, 2007
2007-01-01
It is the belief of the National Scientific Council on the Developing Child that better public understanding of the rapidly growing science of early childhood and early brain development can provide a powerful impetus for the design and implementation of policies and programs that could make a significant difference in the lives of all children.…
How the embryonic chick brain twists.
Chen, Zi; Guo, Qiaohang; Dai, Eric; Forsch, Nickolas; Taber, Larry A
2016-11-01
During early development, the tubular embryonic chick brain undergoes a combination of progressive ventral bending and rightward torsion, one of the earliest organ-level left-right asymmetry events in development. Existing evidence suggests that bending is caused by differential growth, but the mechanism for the predominantly rightward torsion of the embryonic brain tube remains poorly understood. Here, we show through a combination of in vitro experiments, a physical model of the embryonic morphology and mechanics analysis that the vitelline membrane (VM) exerts an external load on the brain that drives torsion. Our theoretical analysis showed that the force is of the order of 10 micronewtons. We also designed an experiment to use fluid surface tension to replace the mechanical role of the VM, and the estimated magnitude of the force owing to surface tension was shown to be consistent with the above theoretical analysis. We further discovered that the asymmetry of the looping heart determines the chirality of the twisted brain via physical mechanisms, demonstrating the mechanical transfer of left-right asymmetry between organs. Our experiments also implied that brain flexure is a necessary condition for torsion. Our work clarifies the mechanical origin of torsion and the development of left-right asymmetry in the early embryonic brain. © 2016 The Author(s).
Deniz Can, Dilara; Richards, Todd; Kuhl, Patricia K
2013-01-01
Magnetic resonance imaging (MRI) brain scans were obtained from 19 infants at 7 months. Expressive and receptive language performance was assessed at 12 months. Voxel-based morphometry (VBM) identified brain regions where gray-matter and white-matter concentrations at 7 months correlated significantly with children's language scores at 12 months. Early gray-matter concentration in the right cerebellum, early white-matter concentration in the right cerebellum, and early white-matter concentration in the left posterior limb of the internal capsule (PLIC)/cerebral peduncle were positively and strongly associated with infants' receptive language ability at 12 months. Early gray-matter concentration in the right hippocampus was positively and strongly correlated with infants' expressive language ability at 12 months. Our results suggest that the cerebellum, PLIC/cerebral peduncle, and the hippocampus may be associated with early language development. Potential links between these structural predictors and infants' linguistic functions are discussed. Copyright © 2012 Elsevier Inc. All rights reserved.
The Case for Musical Instrument Training in Cerebral Palsy for Neurorehabilitation
2016-01-01
Recent imaging studies in cerebral palsy (CP) have described several brain structural changes, functional alterations, and neuroplastic processes that take place after brain injury during early development. These changes affect motor pathways as well as sensorimotor networks. Several of these changes correlate with behavioral measures of motor and sensory disability. It is now widely acknowledged that management of sensory deficits is relevant for rehabilitation in CP. Playing a musical instrument demands the coordination of hand movements with integrated auditory, visual, and tactile feedback, in a process that recruits multiple brain regions. These multiple demands during instrument playing, together with the entertaining character of music, have led to the development and investigation of music-supported therapies, especially for rehabilitation with motor disorders resulting from brain damage. We review scientific evidence that supports the use of musical instrument playing for rehabilitation in CP. We propose that active musical instrument playing may be an efficient means for triggering neuroplastic processes necessary for the development of sensorimotor skills in patients with early brain damage. We encourage experimental research on neuroplasticity and on its impact on the physical and personal development of individuals with CP. PMID:27867664
The Case for Musical Instrument Training in Cerebral Palsy for Neurorehabilitation.
Alves-Pinto, Ana; Turova, Varvara; Blumenstein, Tobias; Lampe, Renée
2016-01-01
Recent imaging studies in cerebral palsy (CP) have described several brain structural changes, functional alterations, and neuroplastic processes that take place after brain injury during early development. These changes affect motor pathways as well as sensorimotor networks. Several of these changes correlate with behavioral measures of motor and sensory disability. It is now widely acknowledged that management of sensory deficits is relevant for rehabilitation in CP. Playing a musical instrument demands the coordination of hand movements with integrated auditory, visual, and tactile feedback, in a process that recruits multiple brain regions. These multiple demands during instrument playing, together with the entertaining character of music, have led to the development and investigation of music-supported therapies, especially for rehabilitation with motor disorders resulting from brain damage. We review scientific evidence that supports the use of musical instrument playing for rehabilitation in CP. We propose that active musical instrument playing may be an efficient means for triggering neuroplastic processes necessary for the development of sensorimotor skills in patients with early brain damage. We encourage experimental research on neuroplasticity and on its impact on the physical and personal development of individuals with CP.
Brooks, Samantha J; Dalvie, Shareefa; Cuzen, Natalie L; Cardenas, Valerie; Fein, George; Stein, Dan J
2014-06-01
Previous neuroimaging studies link both alcohol use disorder (AUD) and early adversity to neurobiological differences in the adult brain. However, the association between AUD and childhood adversity and effects on the developing adolescent brain are less clear, due in part to the confound of psychiatric comorbidity. Here we examine early life adversity and its association with brain volume in a unique sample of 116 South African adolescents (aged 12-16) with AUD but without psychiatric comorbidity. Participants were 58 adolescents with DSM-IV alcohol dependence and with no other psychiatric comorbidities, and 58 age-, gender- and protocol-matched light/non-drinking controls (HC). Assessments included the Childhood Trauma Questionnaire (CTQ). MR images were acquired on a 3T Siemens Magnetom Allegra scanner. Volumes of global and regional structures were estimated using SPM8 Voxel Based Morphometry (VBM), with analysis of covariance (ANCOVA) and regression analyses. In whole brain ANCOVA analyses, a main effect of group when examining the AUD effect after covarying out CTQ was observed on brain volume in bilateral superior temporal gyrus. Subsequent regression analyses to examine how childhood trauma scores are linked to brain volumes in the total cohort revealed a negative correlation in the left hippocampus and right precentral gyrus. Furthermore, bilateral (but most significantly left) hippocampal volume was negatively associated with sub-scores on the CTQ in the total cohort. These findings support our view that some alterations found in brain volumes in studies of adolescent AUD may reflect the impact of confounding factors such as psychiatric comorbidity rather than the effects of alcohol per se. In particular, early life adversity may influence the developing adolescent brain in specific brain regions, such as the hippocampus.
Poverty, Stress, and Brain Development: New Directions for Prevention and Intervention.
Blair, Clancy; Raver, C Cybele
2016-04-01
We review some of the growing evidence of the costs of poverty to children's neuroendocrine function, early brain development, and cognitive ability. We underscore the importance of addressing the negative consequences of poverty-related adversity early in children's lives, given evidence supporting the plasticity of executive functions and associated physiologic processes in response to early intervention and the importance of higher order cognitive functions for success in school and in life. Finally, we highlight some new directions for prevention and intervention that are rapidly emerging at the intersection of developmental science, pediatrics, child psychology and psychiatry, and public policy. Copyright © 2016 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.
Chen, Yasheng; Zhu, Hongtu; An, Hongyu; Armao, Diane; Shen, Dinggang; Gilmore, John H.; Lin, Weili
2013-01-01
The aim of this study was to characterize the maturational changes of the three eigenvalues (λ1 ≥ λ2 ≥ λ3) of diffusion tensor imaging (DTI) during early postnatal life for more insights into early brain development. In order to overcome the limitations of using presumed growth trajectories for regression analysis, we employed Multivariate Adaptive Regression Splines (MARS) to derive data-driven growth trajectories for the three eigenvalues. We further employed Generalized Estimating Equations (GEE) to carry out statistical inferences on the growth trajectories obtained with MARS. With a total of 71 longitudinal datasets acquired from 29 healthy, full-term pediatric subjects, we found that the growth velocities of the three eigenvalues were highly correlated, but significantly different from each other. This paradox suggested the existence of mechanisms coordinating the maturations of the three eigenvalues even though different physiological origins may be responsible for their temporal evolutions. Furthermore, our results revealed the limitations of using the average of λ2 and λ3 as the radial diffusivity in interpreting DTI findings during early brain development because these two eigenvalues had significantly different growth velocities even in central white matter. In addition, based upon the three eigenvalues, we have documented the growth trajectory differences between central and peripheral white matter, between anterior and posterior limbs of internal capsule, and between inferior and superior longitudinal fasciculus. Taken together, we have demonstrated that more insights into early brain maturation can be gained through analyzing eigen-structural elements of DTI. PMID:23455648
Webb, Alexandra R.; Heller, Howard T.; Benson, Carol B.; Lahav, Amir
2015-01-01
Brain development is largely shaped by early sensory experience. However, it is currently unknown whether, how early, and to what extent the newborn’s brain is shaped by exposure to maternal sounds when the brain is most sensitive to early life programming. The present study examined this question in 40 infants born extremely prematurely (between 25- and 32-wk gestation) in the first month of life. Newborns were randomized to receive auditory enrichment in the form of audio recordings of maternal sounds (including their mother’s voice and heartbeat) or routine exposure to hospital environmental noise. The groups were otherwise medically and demographically comparable. Cranial ultrasonography measurements were obtained at 30 ± 3 d of life. Results show that newborns exposed to maternal sounds had a significantly larger auditory cortex (AC) bilaterally compared with control newborns receiving standard care. The magnitude of the right and left AC thickness was significantly correlated with gestational age but not with the duration of sound exposure. Measurements of head circumference and the widths of the frontal horn (FH) and the corpus callosum (CC) were not significantly different between the two groups. This study provides evidence for experience-dependent plasticity in the primary AC before the brain has reached full-term maturation. Our results demonstrate that despite the immaturity of the auditory pathways, the AC is more adaptive to maternal sounds than environmental noise. Further studies are needed to better understand the neural processes underlying this early brain plasticity and its functional implications for future hearing and language development. PMID:25713382
A Developmental Neuroscience Approach to the Search for Biomarkers in Autism Spectrum Disorder
Varcin, Kandice J.; Nelson, Charles A.
2016-01-01
Purpose of review The delineation of biomarkers in autism spectrum disorder (ASD) offers a promising approach to inform precision-medicine based approaches to ASD diagnosis and treatment and to move toward a mechanistic description of the disorder. However, biomarkers with sufficient sensitivity or specificity for clinical application in ASD are yet to be realized. Here, we review recent evidence for early, low-level alterations in brain and behavior development that may offer promising avenues for biomarker development in ASD. Recent findings Accumulating evidence suggests that signs associated with ASD may unfold in a manner that maps onto the hierarchical organization of brain development. Genetic and neuroimaging evidence points towards perturbations in brain development early in life, and emerging evidence indicates that sensorimotor development may be amongst the earliest emerging signs associated with ASD, preceding social and cognitive impairment. Summary The search for biomarkers of risk, prediction and stratification in ASD may be advanced through a developmental neuroscience approach that looks outside of the core signs of ASD and considers the bottom-up nature of brain development alongside the dynamic nature of development over time. We provide examples of assays that could be incorporated in studies to target low-level circuits. PMID:26953849
Neonatal brain resting-state functional connectivity imaging modalities.
Mohammadi-Nejad, Ali-Reza; Mahmoudzadeh, Mahdi; Hassanpour, Mahlegha S; Wallois, Fabrice; Muzik, Otto; Papadelis, Christos; Hansen, Anne; Soltanian-Zadeh, Hamid; Gelovani, Juri; Nasiriavanaki, Mohammadreza
2018-06-01
Infancy is the most critical period in human brain development. Studies demonstrate that subtle brain abnormalities during this state of life may greatly affect the developmental processes of the newborn infants. One of the rapidly developing methods for early characterization of abnormal brain development is functional connectivity of the brain at rest. While the majority of resting-state studies have been conducted using magnetic resonance imaging (MRI), there is clear evidence that resting-state functional connectivity (rs-FC) can also be evaluated using other imaging modalities. The aim of this review is to compare the advantages and limitations of different modalities used for the mapping of infants' brain functional connectivity at rest. In addition, we introduce photoacoustic tomography, a novel functional neuroimaging modality, as a complementary modality for functional mapping of infants' brain.
Sigmund Freud-early network theories of the brain.
Surbeck, Werner; Killeen, Tim; Vetter, Johannes; Hildebrandt, Gerhard
2018-06-01
Since the early days of modern neuroscience, psychological models of brain function have been a key component in the development of new knowledge. These models aim to provide a framework that allows the integration of discoveries derived from the fundamental disciplines of neuroscience, including anatomy and physiology, as well as clinical neurology and psychiatry. During the initial stages of his career, Sigmund Freud (1856-1939), became actively involved in these nascent fields with a burgeoning interest in functional neuroanatomy. In contrast to his contemporaries, Freud was convinced that cognition could not be localised to separate modules and that the brain processes cognition not in a merely serial manner but in a parallel and dynamic fashion-anticipating fundamental aspects of current network theories of brain function. This article aims to shed light on Freud's seminal, yet oft-overlooked, early work on functional neuroanatomy and his reasons for finally abandoning the conventional neuroscientific "brain-based" reference frame in order to conceptualise the mind from a purely psychological perspective.
Rodent Zic Genes in Neural Network Wiring.
Herrera, Eloísa
2018-01-01
The formation of the nervous system is a multistep process that yields a mature brain. Failure in any of the steps of this process may cause brain malfunction. In the early stages of embryonic development, neural progenitors quickly proliferate and then, at a specific moment, differentiate into neurons or glia. Once they become postmitotic neurons, they migrate to their final destinations and begin to extend their axons to connect with other neurons, sometimes located in quite distant regions, to establish different neural circuits. During the last decade, it has become evident that Zic genes, in addition to playing important roles in early development (e.g., gastrulation and neural tube closure), are involved in different processes of late brain development, such as neuronal migration, axon guidance, and refinement of axon terminals. ZIC proteins are therefore essential for the proper wiring and connectivity of the brain. In this chapter, we review our current knowledge of the role of Zic genes in the late stages of neural circuit formation.
TALE transcription factors during early development of the vertebrate brain and eye.
Schulte, Dorothea; Frank, Dale
2014-01-01
Our brain's cognitive performance arises from the coordinated activities of billions of nerve cells. Despite a high degree of morphological and functional differences, all neurons of the vertebrate central nervous system (CNS) arise from a common field of multipotent progenitors. Cell fate specification and differentiation are directed by multistep processes that include inductive/external cues, such as the extracellular matrix or growth factors, and cell-intrinsic determinants, such as transcription factors and epigenetic modulators of proteins and DNA. Here we review recent findings implicating TALE-homeodomain proteins in these processes. Although originally identified as HOX-cofactors, TALE proteins also contribute to many physiological processes that do not require HOX-activity. Particular focus is, therefore, given to HOX-dependent and -independent functions of TALE proteins during early vertebrate brain development. Additionally, we provide an overview about known upstream and downstream factors of TALE proteins in the developing vertebrate brain and discuss general concepts of how TALE proteins function to modulate neuronal cell fate specification. Copyright © 2013 Wiley Periodicals, Inc.
Schrötter, Andreas; Magraoui, Fouzi El; Gröttrup, Bernd; Wiltfang, Jens; Heinsen, Helmut; Marcus, Katrin; Meyer, Helmut E; Grinberg, Lea T; Park, Young Mok
2013-10-01
The HUPO Brain Proteome Project (HUPO BPP) held its 19th workshop in Dortmund, Germany, from May 22 to 24, 2013. The focus of the spring workshop was on strategies and developments concerning early diagnosis of neurodegenerative diseases. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Yang, C-J; Tan, H-P; Du, Y-J
2014-05-16
Autism is a developmental disorder defined by the presence of a triad of communication, social and stereo typical behavioral characteristics with onset before 3years of age. In spite of the fact that there are potential environmental factors for autistic behavior, the dysfunction of serotonin during early development of the brain could be playing a role in this prevalence rise. Serotonin can modulate a number of developmental events, including cell division, neuronal migration, cell differentiation and synaptogenesis. Hyperserotonemia during fetal development results in the loss of serotonin terminals through negative feedback. The increased serotonin causes a decrease of oxytocin in the paraventricular nucleus of the hypothalamus and an increase in calcitonin gene-related peptide (CGRP) in the central nucleus of the amygdale, which are associated with social interactions and vital in autism. However, hyposerotonemia may be also relevant to the development of sensory as well as motor and cognitive faculties. And the paucity of placenta-derived serotonin should have potential importance when the pathogenesis of autism is considered. This review briefly summarized the developmental disruptions of serotonin signaling involved in the pathogenesis of autism during early development of the brain. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.
USDA-ARS?s Scientific Manuscript database
Recent studies have shown associations between maternal obesity at pre- or early pregnancy and long-term neurodevelopment in children, suggesting in utero effects of maternal obesity on offspring brain development. In this study, we examined whether brain functional connectivity to the prefrontal lo...
Early life stress-induced alterations in rat brain structures measured with high resolution MRI.
Sarabdjitsingh, R Angela; Loi, Manila; Joëls, Marian; Dijkhuizen, Rick M; van der Toorn, Annette
2017-01-01
Adverse experiences early in life impair cognitive function both in rodents and humans. In humans this increases the vulnerability to develop mental illnesses while in the rodent brain early life stress (ELS) abnormalities are associated with changes in synaptic plasticity, excitability and microstructure. Detailed information on the effects of ELS on rodent brain structural integrity at large and connectivity within the brain is currently lacking; this information is highly relevant for understanding the mechanism by which early life stress predisposes to mental illnesses. Here, we exposed rats to 24 hours of maternal deprivation (MD) at postnatal day 3, a paradigm known to increase corticosterone levels and thereby activate glucocorticoid receptors in the brain. Using structural magnetic resonance imaging we examined: i) volumetric changes and white/grey matter properties of the whole cerebrum and of specific brain areas; and ii) whether potential alterations could be normalized by blocking glucocorticoid receptors with mifepristone during the critical developmental window of early adolescence, i.e. between postnatal days 26 and 28. The results show that MD caused a volumetric reduction of the prefrontal cortex, particularly the ventromedial part, and the orbitofrontal cortex. Within the whole cerebrum, white (relative to grey) matter volume was decreased and region-specifically in prefrontal cortex and dorsomedial striatum following MD. A trend was found for the hippocampus. Grey matter fractions were not affected. Treatment with mifepristone did not normalize these changes. This study indicates that early life stress in rodents has long lasting consequences for the volume and structural integrity of the brain. However, changes were relatively modest and-unlike behavior- not mitigated by blockade of glucocorticoid receptors during a critical developmental period.
Psychoneuroimmunology of Early-Life Stress: The Hidden Wounds of Childhood Trauma?
Danese, Andrea; J Lewis, Stephanie
2017-01-01
The brain and the immune system are not fully formed at birth, but rather continue to mature in response to the postnatal environment. The two-way interaction between the brain and the immune system makes it possible for childhood psychosocial stressors to affect immune system development, which in turn can affect brain development and its long-term functioning. Drawing from experimental animal models and observational human studies, we propose that the psychoneuroimmunology of early-life stress can offer an innovative framework to understand and treat psychopathology linked to childhood trauma. Early-life stress predicts later inflammation, and there are striking analogies between the neurobiological correlates of early-life stress and of inflammation. Furthermore, there are overlapping trans-diagnostic patterns of association of childhood trauma and inflammation with clinical outcomes. These findings suggest new strategies to remediate the effect of childhood trauma before the onset of clinical symptoms, such as anti-inflammatory interventions and potentiation of adaptive immunity. Similar strategies might be used to ameliorate the unfavorable treatment response described in psychiatric patients with a history of childhood trauma. PMID:27629365
Imaging blood-brain barrier dysfunction as a biomarker for epileptogenesis.
Bar-Klein, Guy; Lublinsky, Svetlana; Kamintsky, Lyn; Noyman, Iris; Veksler, Ronel; Dalipaj, Hotjensa; Senatorov, Vladimir V; Swissa, Evyatar; Rosenbach, Dror; Elazary, Netta; Milikovsky, Dan Z; Milk, Nadav; Kassirer, Michael; Rosman, Yossi; Serlin, Yonatan; Eisenkraft, Arik; Chassidim, Yoash; Parmet, Yisrael; Kaufer, Daniela; Friedman, Alon
2017-06-01
A biomarker that will enable the identification of patients at high-risk for developing post-injury epilepsy is critically required. Microvascular pathology and related blood-brain barrier dysfunction and neuroinflammation were shown to be associated with epileptogenesis after injury. Here we used prospective, longitudinal magnetic resonance imaging to quantitatively follow blood-brain barrier pathology in rats following status epilepticus, late electrocorticography to identify epileptic animals and post-mortem immunohistochemistry to confirm blood-brain barrier dysfunction and neuroinflammation. Finally, to test the pharmacodynamic relevance of the proposed biomarker, two anti-epileptogenic interventions were used; isoflurane anaesthesia and losartan. Our results show that early blood-brain barrier pathology in the piriform network is a sensitive and specific predictor (area under the curve of 0.96, P < 0.0001) for epilepsy, while diffused pathology is associated with a lower risk. Early treatments with either isoflurane anaesthesia or losartan prevented early microvascular damage and late epilepsy. We suggest quantitative assessment of blood-brain barrier pathology as a clinically relevant predictive, diagnostic and pharmaco!dynamics biomarker for acquired epilepsy. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
Brain Tumor Image Segmentation in MRI Image
NASA Astrophysics Data System (ADS)
Peni Agustin Tjahyaningtijas, Hapsari
2018-04-01
Brain tumor segmentation plays an important role in medical image processing. Treatment of patients with brain tumors is highly dependent on early detection of these tumors. Early detection of brain tumors will improve the patient’s life chances. Diagnosis of brain tumors by experts usually use a manual segmentation that is difficult and time consuming because of the necessary automatic segmentation. Nowadays automatic segmentation is very populer and can be a solution to the problem of tumor brain segmentation with better performance. The purpose of this paper is to provide a review of MRI-based brain tumor segmentation methods. There are number of existing review papers, focusing on traditional methods for MRI-based brain tumor image segmentation. this paper, we focus on the recent trend of automatic segmentation in this field. First, an introduction to brain tumors and methods for brain tumor segmentation is given. Then, the state-of-the-art algorithms with a focus on recent trend of full automatic segmentaion are discussed. Finally, an assessment of the current state is presented and future developments to standardize MRI-based brain tumor segmentation methods into daily clinical routine are addressed.
ERIC Educational Resources Information Center
Poulsen, Catherine; Picton, Terence W.; Paus, Tomas
2009-01-01
Maturational changes in the capacity to process quickly the temporal envelope of sound have been linked to language abilities in typically developing individuals. As part of a longitudinal study of brain maturation and cognitive development during adolescence, we employed dense-array EEG and spatiotemporal source analysis to characterize…
The Neuroanatomy of the Autistic Phenotype
ERIC Educational Resources Information Center
Fahim, Cherine; Meguid, Nagwa A.; Nashaat, Neveen H.; Yoon, Uicheul; Mancini-Marie, Adham; Evans, Alan C.
2012-01-01
The autism phenotype is associated with an excess of brain volume due in part to decreased pruning during development. Here we aimed at assessing brain volume early in development to further elucidate previous findings in autism and determine whether this pattern is restricted to idiopathic autism or shared within the autistic phenotype (fragile X…
Music and the Brain in Childhood Development. Review of Research.
ERIC Educational Resources Information Center
Strickland, Susan J.
2002-01-01
Reviews literature on effects of music on the brain in childhood development. Areas include: (1) early synaptic growth; (2) nature versus nurture; (3) background music; (4) musical practice; (5) music learning and cognitive skills; (6) transfer of music learning; (7) musical instrument practice; (8) children and music; and (9) transfer effects.…
Chen, Yasheng; An, Hongyu; Zhu, Hongtu; Jewells, Valerie; Armao, Diane; Shen, Dinggang; Gilmore, John H.; Lin, Weili
2011-01-01
Although diffusion tensor imaging (DTI) has provided substantial insights into early brain development, most DTI studies based on fractional anisotropy (FA) and mean diffusivity (MD) may not capitalize on the information derived from the three principal diffusivities (e.g. eigenvalues). In this study, we explored the spatial and temporal evolution of white matter structures during early brain development using two geometrical diffusion measures, namely, linear (Cl) and planar (Cp) diffusion anisotropies, from 71 longitudinal datasets acquired from 29 healthy, full-term pediatric subjects. The growth trajectories were estimated with generalized estimating equations (GEE) using linear fitting with logarithm of age (days). The presence of the white matter structures in Cl and Cp was observed in neonates, suggesting that both the cylindrical and fanning or crossing structures in various white matter regions may already have been formed at birth. Moreover, we found that both Cl and Cp evolved in a temporally nonlinear and spatially inhomogeneous manner. The growth velocities of Cl in central white matter were significantly higher when compared to peripheral, or more laterally located, white matter: central growth velocity Cl = 0.0465±0.0273/log(days), versus peripheral growth velocity Cl=0.0198±0.0127/log(days), p<10−6. In contrast, the growth velocities of Cp in central white matter were significantly lower than that in peripheral white matter: central growth velocity Cp= 0.0014±0.0058/log(days), versus peripheral growth velocity Cp = 0.0289±0.0101/log(days), p<10−6. Depending on the underlying white matter site which is analyzed, our findings suggest that ongoing physiologic and microstructural changes in the developing brain may exert different effects on the temporal evolution of these two geometrical diffusion measures. Thus, future studies utilizing DTI with correlative histological analysis in the study of early brain development are warranted. PMID:21784163
A Monitoring Tool of Infant and Toddler Movement Skills
ERIC Educational Resources Information Center
Leitschuh, Carol A.; Harring, Jeffrey R.; Dunn, Winnie
2014-01-01
Physical activity in infancy is essential for early brain development. Development in the early years is the most rapid at any time during life. Monitoring functional movement skills of infants and toddlers frequently (3-week intervals) and quickly (minutes) produces information on whether development is on track or in need of intervention. To…
Developmental changes in organization of structural brain networks.
Khundrakpam, Budhachandra S; Reid, Andrew; Brauer, Jens; Carbonell, Felix; Lewis, John; Ameis, Stephanie; Karama, Sherif; Lee, Junki; Chen, Zhang; Das, Samir; Evans, Alan C
2013-09-01
Recent findings from developmental neuroimaging studies suggest that the enhancement of cognitive processes during development may be the result of a fine-tuning of the structural and functional organization of brain with maturation. However, the details regarding the developmental trajectory of large-scale structural brain networks are not yet understood. Here, we used graph theory to examine developmental changes in the organization of structural brain networks in 203 normally growing children and adolescents. Structural brain networks were constructed using interregional correlations in cortical thickness for 4 age groups (early childhood: 4.8-8.4 year; late childhood: 8.5-11.3 year; early adolescence: 11.4-14.7 year; late adolescence: 14.8-18.3 year). Late childhood showed prominent changes in topological properties, specifically a significant reduction in local efficiency, modularity, and increased global efficiency, suggesting a shift of topological organization toward a more random configuration. An increase in number and span of distribution of connector hubs was found in this age group. Finally, inter-regional connectivity analysis and graph-theoretic measures indicated early maturation of primary sensorimotor regions and protracted development of higher order association and paralimbic regions. Our finding reveals a time window of plasticity occurring during late childhood which may accommodate crucial changes during puberty and the new developmental tasks that an adolescent faces.
ERIC Educational Resources Information Center
Finch, Jenna E.; Obradovic, Jelena; Yousafzai, Aisha
2016-01-01
Over 200 million children under the age of 5 are not fulfilling their developmental potential due to poverty, poor health, and lack of cognitive stimulation. Experiences in early childhood have long term-effects on brain development and thus the cognitive and social-emotional skills that promote children's school success. Further, early childhood…
ERIC Educational Resources Information Center
Eyler, Lisa T.; Pierce, Karen; Courchesne, Eric
2012-01-01
Failure to develop normal language comprehension is an early warning sign of autism, but the neural mechanisms underlying this signature deficit are unknown. This is because of an almost complete absence of functional studies of the autistic brain during early development. Using functional magnetic resonance imaging, we previously observed a trend…
Adhikari, Mohit H; Raja Beharelle, Anjali; Griffa, Alessandra; Hagmann, Patric; Solodkin, Ana; McIntosh, Anthony R; Small, Steven L; Deco, Gustavo
2015-06-10
Children who sustain a prenatal or perinatal brain injury in the form of a stroke develop remarkably normal cognitive functions in certain areas, with a particular strength in language skills. A dominant explanation for this is that brain regions from the contralesional hemisphere "take over" their functions, whereas the damaged areas and other ipsilesional regions play much less of a role. However, it is difficult to tease apart whether changes in neural activity after early brain injury are due to damage caused by the lesion or by processes related to postinjury reorganization. We sought to differentiate between these two causes by investigating the functional connectivity (FC) of brain areas during the resting state in human children with early brain injury using a computational model. We simulated a large-scale network consisting of realistic models of local brain areas coupled through anatomical connectivity information of healthy and injured participants. We then compared the resulting simulated FC values of healthy and injured participants with the empirical ones. We found that the empirical connectivity values, especially of the damaged areas, correlated better with simulated values of a healthy brain than those of an injured brain. This result indicates that the structural damage caused by an early brain injury is unlikely to have an adverse and sustained impact on the functional connections, albeit during the resting state, of damaged areas. Therefore, these areas could continue to play a role in the development of near-normal function in certain domains such as language in these children. Copyright © 2015 the authors 0270-6474/15/358914-11$15.00/0.
Developmental synchrony of thalamocortical circuits in the neonatal brain.
Poh, Joann S; Li, Yue; Ratnarajah, Nagulan; Fortier, Marielle V; Chong, Yap-Seng; Kwek, Kenneth; Saw, Seang-Mei; Gluckman, Peter D; Meaney, Michael J; Qiu, Anqi
2015-08-01
The thalamus is a deep gray matter structure and consists of axonal fibers projecting to the entire cortex, which provide the anatomical support for its sensorimotor and higher-level cognitive functions. There is limited in vivo evidence on the normal thalamocortical development, especially in early life. In this study, we aimed to investigate the developmental patterns of the cerebral cortex, the thalamic substructures, and their connectivity with the cortex in the first few weeks of the postnatal brain. We hypothesized that there is developmental synchrony of the thalamus, its cortical projections, and corresponding target cortical structures. We employed diffusion tensor imaging (DTI) and divided the thalamus into five substructures respectively connecting to the frontal, precentral, postcentral, temporal, and parietal and occipital cortex. T2-weighted magnetic resonance imaging (MRI) was used to measure cortical thickness. We found age-related increases in cortical thickness of bilateral frontal cortex and left temporal cortex in the early postnatal brain. We also found that the development of the thalamic substructures was synchronized with that of their respective thalamocortical connectivity in the first few weeks of the postnatal life. In particular, the right thalamo-frontal substructure had the fastest growth in the early postnatal brain. Our study suggests that the distinct growth patterns of the thalamic substructures are in synchrony with those of the cortex in early life, which may be critical for the development of the cortical and subcortical functional specialization. Copyright © 2015 Elsevier Inc. All rights reserved.
Brain structure correlates of urban upbringing, an environmental risk factor for schizophrenia.
Haddad, Leila; Schäfer, Axel; Streit, Fabian; Lederbogen, Florian; Grimm, Oliver; Wüst, Stefan; Deuschle, Michael; Kirsch, Peter; Tost, Heike; Meyer-Lindenberg, Andreas
2015-01-01
Urban upbringing has consistently been associated with schizophrenia, but which specific environmental exposures are reflected by this epidemiological observation and how they impact the developing brain to increase risk is largely unknown. On the basis of prior observations of abnormal functional brain processing of social stress in urban-born humans and preclinical evidence for enduring structural brain effects of early social stress, we investigated a possible morphological correlate of urban upbringing in human brain. In a sample of 110 healthy subjects studied with voxel-based morphometry, we detected a strong inverse correlation between early-life urbanicity and gray matter (GM) volume in the right dorsolateral prefrontal cortex (DLPFC, Brodmann area 9). Furthermore, we detected a negative correlation of early-life urbanicity and GM volumes in the perigenual anterior cingulate cortex (pACC) in men only. Previous work has linked volume reductions in the DLPFC to the exposure to psychosocial stress, including stressful experiences in early life. Besides, anatomical and functional alterations of this region have been identified in schizophrenic patients and high-risk populations. Previous data linking functional hyperactivation of pACC during social stress to urban upbringing suggest that the present interaction effect in brain structure might contribute to an increased risk for schizophrenia in males brought up in cities. Taken together, our results suggest a neural mechanism by which early-life urbanicity could impact brain architecture to increase the risk for schizophrenia. © The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.
Neurodevelopmental changes of reading the mind in the eyes
Op de Macks, Zdeňa A.; Güroğlu, Berna; Rombouts, Serge A. R. B.; Van der Molen, Maurits W.; Crone, Eveline A.
2012-01-01
The eyes provide important information for decoding the mental states of others. In this fMRI study we examined how reading the mind in the eyes develops across adolescence and we tested the developmental trajectories of brain regions involved in this basic perceptual mind-reading ability. Participants from three age groups (early adolescents, mid adolescents and young adults) participated in the study and performed an adapted version of the ‘Reading the Mind in the Eyes task’, in which photographs of the eye region of faces were presented. Behavioral results show that the ability to decode the feelings and thoughts of others from the eyes develops before early adolescence. For all ages, brain activity was found in the posterior superior temporal sulcus during reading the mind in the eyes relative to a control condition requiring age and gender judgments using the same eyes stimuli. Only early adolescents showed additional involvement of the medial prefrontal cortex, the inferior frontal gyrus and the temporal pole. The results are discussed in the light of recent findings on the development of the social brain network. PMID:21515640
... ARTICLES Scientific articles. RESEARCH Legacy for Children™ study. Child Development: What's New Article: Differences in health care, family, ... Disorders, Learning Disorders, and other developmental conditions. ... Development Basics Early Brain Development Developmental Screening Screening for ...
Silvestre, David C; Maccioni, Hugo J F; Caputto, Beatriz L
2009-03-01
Although the molecular and cellular basis of particular events that lead to the biogenesis of membranes in eukaryotic cells has been described in detail, understanding of the intrinsic complexity of the pleiotropic response by which a cell adjusts the overall activity of its endomembrane system to accomplish these requirements is limited. Here we carried out an immunocytochemical and biochemical examination of the content and quality of the endoplasmic reticulum (ER) and Golgi apparatus membranes in two in vivo situations characterized by a phase of active cell proliferation followed by a phase of declination in proliferation (rat brain tissue at early and late developmental stages) or by permanent active proliferation (gliomas and their most malignant manifestation, glioblastomas multiforme). It was found that, in highly proliferative phases of brain development (early embryo brain cells), the content of ER and Golgi apparatus membranes, measured as total lipid phosphorous content, is higher than in adult brain cells. In addition, the concentration of protein markers of ER and Golgi is also higher in early embryo brain cells and in human glioblastoma multiforme cells than in adult rat brain or in nonpathological human brain cells. Results suggest that the amount of endomembranes and the concentration of constituent functional proteins diminish as cells decline in their proliferative activity.
Amicuzi, Ileana; Stortini, Massimo; Petrarca, Maurizio; Di Giulio, Paola; Di Rosa, Giuseppe; Fariello, Giuseppe; Longo, Daniela; Cannatà, Vittorio; Genovese, Elisabetta; Castelli, Enrico
2006-10-01
We report the case of a 4.6-year-old girl born pre-term with early bilateral occipital damage. It was revealed that the child had non-severely impaired basic visual abilities and ocular motility, a selective perceptual deficit of figure-ground segregation, impaired visual recognition and abnormal navigating through space. Even if the child's visual functioning was not optimal, this was the expression of adaptive anatomic and functional brain modifications that occurred following the early lesion. Anatomic brain structure was studied with anatomic MRI and Diffusor Tensor Imaging (DTI)-MRI. This behavioral study may provide an important contribution to understanding the impact of an early lesion of the visual system on the development of visual functions and on the immature brain's potential for reorganisation related to when the damage occurred.
Infant Hand Preference and the Development of Cognitive Abilities
Michel, George F.; Campbell, Julie M.; Marcinowski, Emily C.; Nelson, Eliza L.; Babik, Iryna
2016-01-01
Hand preference develops in the first two postnatal years with nearly half of infants exhibiting a consistent early preference for acquiring objects. Others exhibit a more variable developmental trajectory but by the end of their second postnatal year, most exhibit a consistent hand preference for role-differentiated bimanual manipulation. According to some forms of embodiment theory, these differences in hand use patterns should influence the way children interact with their environments, which, in turn, should affect the structure and function of brain development. Such early differences in brain development should result in different trajectories of psychological development. We present evidence that children with consistent early hand preferences exhibit advanced patterns of cognitive development as compared to children who develop a hand preference later. Differences in the developmental trajectory of hand preference are predictive of developmental differences in language, object management skills, and tool-use skills. As predicted by Casasanto’s body-specificity hypothesis, infants with different hand preferences proceed along different developmental pathways of cognitive functioning. PMID:27047431
Jašarević, Eldin; Howerton, Christopher L; Howard, Christopher D; Bale, Tracy L
2015-09-01
The neonate is exposed to the maternal vaginal microbiota during parturition, providing the primary source for normal gut colonization, host immune maturation, and metabolism. These early interactions between the host and microbiota occur during a critical window of neurodevelopment, suggesting early life as an important period of cross talk between the developing gut and brain. Because perturbations in the prenatal environment such as maternal stress increase neurodevelopmental disease risk, disruptions to the vaginal ecosystem could be a contributing factor in significant and long-term consequences for the offspring. Therefore, to examine the hypothesis that changes in the vaginal microbiome are associated with effects on the offspring gut microbiota and on the developing brain, we used genomic, proteomic and metabolomic technologies to examine outcomes in our mouse model of early prenatal stress. Multivariate modeling identified broad proteomic changes to the maternal vaginal environment that influence offspring microbiota composition and metabolic processes essential for normal neurodevelopment. Maternal stress altered proteins related to vaginal immunity and abundance of Lactobacillus, the prominent taxa in the maternal vagina. Loss of maternal vaginal Lactobacillus resulted in decreased transmission of this bacterium to offspring. Further, altered microbiota composition in the neonate gut corresponded with changes in metabolite profiles involved in energy balance, and with region- and sex-specific disruptions of amino acid profiles in the developing brain. Taken together, these results identify the vaginal microbiota as a novel factor by which maternal stress may contribute to reprogramming of the developing brain that may predispose individuals to neurodevelopmental disorders.
Early life stress is associated with default system integrity and emotionality during infancy.
Graham, Alice M; Pfeifer, Jennifer H; Fisher, Philip A; Carpenter, Samuel; Fair, Damien A
2015-11-01
Extensive animal research has demonstrated the vulnerability of the brain to early life stress (ELS) with consequences for emotional development and mental health. However, the influence of moderate and common forms of stress on early human brain development is less well-understood and precisely characterized. To date, most work has focused on severe forms of stress, and/or on brain functioning years after stress exposure. In this report we focused on conflict between parents (interparental conflict), a common and relatively moderate form of ELS that is highly relevant for children's mental health outcomes. We used resting state functional connectivity MRI to examine the coordinated functioning of the infant brain (N = 23; 6-12-months-of-age) in the context of interparental conflict. We focused on the default mode network (DMN) due to its well-characterized developmental trajectory and implications for mental health. We further examined DMN strength as a mediator between conflict and infants' negative emotionality. Higher interparental conflict since birth was associated with infants showing stronger connectivity between two core DMN regions, the posterior cingulate cortex (PCC) and the anterior medial prefrontal cortex (aMPFC). PCC to amygdala connectivity was also increased. Stronger PCC-aMPFC connectivity mediated between higher conflict and higher negative infant emotionality. The developing DMN may be an important marker for effects of ELS with relevance for emotional development and subsequent mental health. Increasing understanding of the associations between common forms of family stress and emerging functional brain networks has potential to inform intervention efforts to improve mental health outcomes. © 2015 Association for Child and Adolescent Mental Health.
Early life stress is associated with default system integrity and emotionality during infancy
Graham, Alice M.; Pfeifer, Jennifer H.; Fisher, Philip A.; Carpenter, Samuel; Fair, Damien A.
2015-01-01
Background Extensive animal research has demonstrated the vulnerability of the brain to early life stress (ELS) with consequences for emotional development and mental health. However, the influence of moderate and common forms of stress on early human brain development is less well understood and precisely characterized. To date, most work has focused on severe forms of stress, and/or on brain functioning years after stress exposure. Methods In this report we focused on conflict between parents (interparental conflict), a common and relatively moderate form of ELS that is highly relevant for children's mental health outcomes. We used resting state functional connectivity MRI to examine the coordinated functioning of the infant brain (N=23; 6–12-months-of-age) in the context of interparental conflict. We focused on the default mode network (DMN) due to its well characterized developmental trajectory and implications for mental health. We further examined DMN strength as a mediator between conflict and infants’ negative emotionality. Results Higher interparental conflict since birth was associated with infants showing stronger connectivity between two core DMN regions, the posterior cingulate cortex (PCC) and the anterior medial prefrontal cortex (aMPFC). PCC to amygdala connectivity was also increased. Stronger PCC-aMPFC connectivity mediated between higher conflict and higher negative infant emotionality. Conclusions The developing DMN may be an important marker for effects of ELS with relevance for emotional development and subsequent mental health. Increasing understanding of the associations between common forms of family stress and emerging functional brain networks has potential to inform intervention efforts to improve mental health outcomes. PMID:25809052
Development of a brain MRI-based hidden Markov model for dementia recognition
2013-01-01
Background Dementia is an age-related cognitive decline which is indicated by an early degeneration of cortical and sub-cortical structures. Characterizing those morphological changes can help to understand the disease development and contribute to disease early prediction and prevention. But modeling that can best capture brain structural variability and can be valid in both disease classification and interpretation is extremely challenging. The current study aimed to establish a computational approach for modeling the magnetic resonance imaging (MRI)-based structural complexity of the brain using the framework of hidden Markov models (HMMs) for dementia recognition. Methods Regularity dimension and semi-variogram were used to extract structural features of the brains, and vector quantization method was applied to convert extracted feature vectors to prototype vectors. The output VQ indices were then utilized to estimate parameters for HMMs. To validate its accuracy and robustness, experiments were carried out on individuals who were characterized as non-demented and mild Alzheimer's diseased. Four HMMs were constructed based on the cohort of non-demented young, middle-aged, elder and demented elder subjects separately. Classification was carried out using a data set including both non-demented and demented individuals with a wide age range. Results The proposed HMMs have succeeded in recognition of individual who has mild Alzheimer's disease and achieved a better classification accuracy compared to other related works using different classifiers. Results have shown the ability of the proposed modeling for recognition of early dementia. Conclusion The findings from this research will allow individual classification to support the early diagnosis and prediction of dementia. By using the brain MRI-based HMMs developed in our proposed research, it will be more efficient, robust and can be easily used by clinicians as a computer-aid tool for validating imaging bio-markers for early prediction of dementia. PMID:24564961
Functional Brain Organization for Number Processing in Pre-Verbal Infants
ERIC Educational Resources Information Center
Edwards, Laura A.; Wagner, Jennifer B.; Simon, Charline E.; Hyde, Daniel C.
2016-01-01
Humans are born with the ability to mentally represent the approximate numerosity of a set of objects, but little is known about the brain systems that sub-serve this ability early in life and their relation to the brain systems underlying symbolic number and mathematics later in development. Here we investigate processing of numerical magnitudes…
Insulin Action in Brain Regulates Systemic Metabolism and Brain Function
Kleinridders, André; Ferris, Heather A.; Cai, Weikang
2014-01-01
Insulin receptors, as well as IGF-1 receptors and their postreceptor signaling partners, are distributed throughout the brain. Insulin acts on these receptors to modulate peripheral metabolism, including regulation of appetite, reproductive function, body temperature, white fat mass, hepatic glucose output, and response to hypoglycemia. Insulin signaling also modulates neurotransmitter channel activity, brain cholesterol synthesis, and mitochondrial function. Disruption of insulin action in the brain leads to impairment of neuronal function and synaptogenesis. In addition, insulin signaling modulates phosphorylation of tau protein, an early component in the development of Alzheimer disease. Thus, alterations in insulin action in the brain can contribute to metabolic syndrome, and the development of mood disorders and neurodegenerative diseases. PMID:24931034
Matsuda, Ken Ichi; Mori, Hiroko; Nugent, Bridget M; Pfaff, Donald W; McCarthy, Margaret M; Kawata, Mitsuhiro
2011-07-01
Epigenetic histone modifications are emerging as important mechanisms for conveyance of and maintenance of effects of the hormonal milieu to the developing brain. We hypothesized that alteration of histone acetylation status early in development by sex steroid hormones is important for sexual differentiation of the brain. It was found that during the critical period for sexual differentiation, histones associated with promoters of essential genes in masculinization of the brain (estrogen receptor α and aromatase) in the medial preoptic area, an area necessary for male sexual behavior, were differentially acetylated between the sexes. Consistent with these findings, binding of histone deacetylase (HDAC) 2 and 4 to the promoters was higher in males than in females. To examine the involvement of histone deacetylation on masculinization of the brain at the behavioral level, we inhibited HDAC in vivo by intracerebroventricular infusion of the HDAC inhibitor trichostatin A or antisense oligodeoxynucleotide directed against the mRNA for HDAC2 and -4 in newborn male rats. Aspects of male sexual behavior in adulthood were significantly reduced by administration of either trichostatin A or antisense oligodeoxynucleotide. These results demonstrate that HDAC activity during the early postnatal period plays a crucial role in the masculinization of the brain via modifications of histone acetylation status.
The Neonatal Connectome During Preterm Brain Development
van den Heuvel, Martijn P.; Kersbergen, Karina J.; de Reus, Marcel A.; Keunen, Kristin; Kahn, René S.; Groenendaal, Floris; de Vries, Linda S.; Benders, Manon J.N.L.
2015-01-01
The human connectome is the result of an elaborate developmental trajectory. Acquiring diffusion-weighted imaging and resting-state fMRI, we studied connectome formation during the preterm phase of macroscopic connectome genesis. In total, 27 neonates were scanned at week 30 and/or week 40 gestational age (GA). Examining the architecture of the neonatal anatomical brain network revealed a clear presence of a small-world modular organization before term birth. Analysis of neonatal functional connectivity (FC) showed the early formation of resting-state networks, suggesting that functional networks are present in the preterm brain, albeit being in an immature state. Moreover, structural and FC patterns of the neonatal brain network showed strong overlap with connectome architecture of the adult brain (85 and 81%, respectively). Analysis of brain development between week 30 and week 40 GA revealed clear developmental effects in neonatal connectome architecture, including a significant increase in white matter microstructure (P < 0.01), small-world topology (P < 0.01) and interhemispheric FC (P < 0.01). Computational analysis further showed that developmental changes involved an increase in integration capacity of the connectivity network as a whole. Taken together, we conclude that hallmark organizational structures of the human connectome are present before term birth and subject to early development. PMID:24833018
Calderón-Garcidueñas, Lilian; Franco-Lira, Maricela; Mora-Tiscareño, Antonieta; Medina-Cortina, Humberto; Torres-Jardón, Ricardo; Kavanaugh, Michael
2013-01-01
Chronic exposure to particulate matter air pollution is known to cause inflammation leading to respiratory- and cardiovascular-related sickness and death. Mexico City Metropolitan Area children exhibit an early brain imbalance in genes involved in oxidative stress, inflammation, and innate and adaptive immune responses. Early dysregulated neuroinflammation, brain microvascular damage, production of potent vasoconstrictors, and perturbations in the integrity of the neurovascular unit likely contribute to progressive neurodegenerative processes. The accumulation of misfolded proteins coincides with the anatomical distribution observed in the early stages of both Alzheimer's and Parkinson's diseases. We contend misfolding of hyperphosphorylated tau (HPπ), alpha-synuclein, and beta-amyloid could represent a compensatory early protective response to the sustained systemic and brain inflammation. However, we favor the view that the chronic systemic and brain dysregulated inflammation and the diffuse vascular damage contribute to the establishment of neurodegenerative processes with childhood clinical manifestations. Friend turns Foe early; therefore, implementation of neuroprotective measures to ameliorate or stop the inflammatory and neurodegenerative processes is warranted in exposed children. Epidemiological, cognitive, structural, and functional neuroimaging and mechanistic studies into the association between air pollution exposures and the development of neuroinflammation and neurodegeneration in children are of pressing importance for public health.
Calderón-Garcidueñas, Lilian; Franco-Lira, Maricela; Mora-Tiscareño, Antonieta; Medina-Cortina, Humberto; Torres-Jardón, Ricardo; Kavanaugh, Michael
2013-01-01
Chronic exposure to particulate matter air pollution is known to cause inflammation leading to respiratory- and cardiovascular-related sickness and death. Mexico City Metropolitan Area children exhibit an early brain imbalance in genes involved in oxidative stress, inflammation, and innate and adaptive immune responses. Early dysregulated neuroinflammation, brain microvascular damage, production of potent vasoconstrictors, and perturbations in the integrity of the neurovascular unit likely contribute to progressive neurodegenerative processes. The accumulation of misfolded proteins coincides with the anatomical distribution observed in the early stages of both Alzheimer's and Parkinson's diseases. We contend misfolding of hyperphosphorylated tau (HPπ), alpha-synuclein, and beta-amyloid could represent a compensatory early protective response to the sustained systemic and brain inflammation. However, we favor the view that the chronic systemic and brain dysregulated inflammation and the diffuse vascular damage contribute to the establishment of neurodegenerative processes with childhood clinical manifestations. Friend turns Foe early; therefore, implementation of neuroprotective measures to ameliorate or stop the inflammatory and neurodegenerative processes is warranted in exposed children. Epidemiological, cognitive, structural, and functional neuroimaging and mechanistic studies into the association between air pollution exposures and the development of neuroinflammation and neurodegeneration in children are of pressing importance for public health. PMID:23509683
Li, Wen; Li, Zhenshu; Li, Shou; Wang, Xinyan; Wilson, John X.; Huang, Guowei
2018-01-01
Periconceptional maternal folate levels may alter DNA methylation patterns and health outcomes in offspring. We hypothesized that maternal folic acid supplementation alters fetal neural development through DNA methylation in the fetal brain. Twenty-eight rats were randomly assigned to four groups: three groups of the female rats were fed folate-normal, folate-deficient or folate-supplemented diets from seven days before mating to delivery. In another group, folic acid supplementation diet short-period group was fed a folate-normal diet, except for 10 days (begin mating) when this group was fed a folate-supplemented diet. After delivery, the diets were changed to folate-normal diet for all four groups. The cliff avoidance and forelimb grip tests were used to assess sensory motor function of rat offspring. The results indicate that maternal folic acid supplementation improved the early development of sensory-motor function in offspring. Maternal folic acid supplementation increased the methylation potential, global DNA methylation (5-mC) and DNA methyltransferase expression and activity in the brains of the offspring. In conclusion, maternal folic acid supplementation increases DNA methylation pattern in offspring brain and improves the early development of sensory-motor function. PMID:29494536
Reversible brain atrophy in glutaric aciduria type 1.
Numata-Uematsu, Yurika; Sakamoto, Osamu; Kakisaka, Yosuke; Okubo, Yukimune; Oikawa, Yoshitsugu; Arai-Ichinoi, Natsuko; Kure, Shigeo; Uematsu, Mitsugu
2017-06-01
Glutaric aciduria type 1 (GA1) is a rare metabolic disorder caused by a deficiency of glutaryl-CoA dehydrogenase. The typical clinical onset features an acute encephalopathic crisis developed in early childhood, causing irreversible striatal injury. Recently, tandem mass spectrometry of spots of dried blood has allowed pre-symptomatic detection of GA1 in newborns. Early treatment can prevent irreversible neurological injury. We report the case of a girl with GA1 who exhibited a characteristic reversible change upon brain magnetic resonance imaging (MRI). She was diagnosed with GA1 as a newborn. She commenced dietary carnitine and her intake of lysine and tryptophan were reduced at the age of 4weeks. After treatment commenced, her mean glutarylcarnitine level was lower than that in the previous reports. The plasma lysine and tryptophan levels were maintained below the normal ranges. At 4months, brain MRI revealed a widened operculum with dilatation of the subarachnoid spaces surrounding the atrophic bilateral frontotemporal lobes; this is typical of GA1 patients. However, at 17months, MRI revealed that the atrophic lesion had disappeared and she subsequently underwent normal maturation. She has never suffered a metabolic decompensation episode. At 26months, her development and brain MRI were normal. The present reversible brain atrophy in a patient with GA1 indicates that early dietary modifications with a lower level of glutarylcarnitine and administration of carnitine can lead to normal development. Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.
Effects of Early Serotonin Programming on Fear Response, Memory and Aggression
USDA-ARS?s Scientific Manuscript database
The neurotransmitter serotonin (5-HT) also acts as a neurogenic compound in the developing brain. Early administration of a 5-HT agonist could alter development of serotonergic circuitry, altering behaviors mediated by 5-HT signaling, including memory, fear and aggression. The present study was desi...
USDA-ARS?s Scientific Manuscript database
Serotonin (5-HT) acts as a neurogenic compound in the developing brain; however serotonin altering drugs such as SSRIs are often prescribed to pregnant and lactating mothers. Early agonism of 5-HT receptors could alter the development of serotonergic circuitry, altering neurotransmission and behavio...
Sexual differentiation of the brain occurs during late gestation through the early postnatal period. The development of the phenotypical male brain is dependent on the aromatization of circulating testosterone to estradiol. Exposure to endocrine disrupting chemicals (EDCs) duri...
Identification of neural biomarkers of altered sexual differentiation following gestational exposure
Sexual differentiation of the brain occurs during late gestation through the early postnatal period. The development of the phenotypical male brain is dependent on the aromatization of circulating testosterone to estradiol. Exposure to endocrine disrupting chemicals (EDCs) during...
Sexual differentiation of the brain occurs during late gestation through the early postnatal period. The development of the phenotypical male brain is dependent on the aromatization of circulating testosterone to estradiol. Exposure to endocrine disrupting chemicals (EDCs) duri...
The maturing architecture of the brain's default network
Fair, Damien A.; Cohen, Alexander L.; Dosenbach, Nico U. F.; Church, Jessica A.; Miezin, Francis M.; Barch, Deanna M.; Raichle, Marcus E.; Petersen, Steven E.; Schlaggar, Bradley L.
2008-01-01
In recent years, the brain's “default network,” a set of regions characterized by decreased neural activity during goal-oriented tasks, has generated a significant amount of interest, as well as controversy. Much of the discussion has focused on the relationship of these regions to a “default mode” of brain function. In early studies, investigators suggested that, the brain's default mode supports “self-referential” or “introspective” mental activity. Subsequently, regions of the default network have been more specifically related to the “internal narrative,” the “autobiographical self,” “stimulus independent thought,” “mentalizing,” and most recently “self-projection.” However, the extant literature on the function of the default network is limited to adults, i.e., after the system has reached maturity. We hypothesized that further insight into the network's functioning could be achieved by characterizing its development. In the current study, we used resting-state functional connectivity MRI (rs-fcMRI) to characterize the development of the brain's default network. We found that the default regions are only sparsely functionally connected at early school age (7–9 years old); over development, these regions integrate into a cohesive, interconnected network. PMID:18322013
Horton, Megan K; Margolis, Amy E; Tang, Cheuk; Wright, Robert
2014-04-01
The prevalence of childhood neurodevelopmental disorders has been increasing over the last several decades. Prenatal and early childhood exposure to environmental toxicants is increasingly recognized as contributing to the growing rate of neurodevelopmental disorders. Very little information is known about the mechanistic processes by which environmental chemicals alter brain development. We review the recent advances in brain imaging modalities and discuss their application in epidemiologic studies of prenatal and early childhood exposure to environmental toxicants. Neuroimaging techniques (volumetric and functional MRI, diffusor tensor imaging, and magnetic resonance spectroscopy) have opened unprecedented access to study the developing human brain. These techniques are noninvasive and free of ionization radiation making them suitable for research applications in children. Using these techniques, we now understand much about structural and functional patterns in the typically developing brain. This knowledge allows us to investigate how prenatal exposure to environmental toxicants may alter the typical developmental trajectory. MRI is a powerful tool that allows in-vivo visualization of brain structure and function. Used in epidemiologic studies of environmental exposure, it offers the promise to causally link exposure with behavioral and cognitive manifestations and ultimately to inform programs to reduce exposure and mitigate adverse effects of exposure.
Prenatal cocaine effects on brain structure in early infancy.
Grewen, Karen; Burchinal, Margaret; Vachet, Clement; Gouttard, Sylvain; Gilmore, John H; Lin, Weili; Johns, Josephine; Elam, Mala; Gerig, Guido
2014-11-01
Prenatal cocaine exposure (PCE) is related to subtle deficits in cognitive and behavioral function in infancy, childhood and adolescence. Very little is known about the effects of in utero PCE on early brain development that may contribute to these impairments. The purpose of this study was to examine brain structural differences in infants with and without PCE. We conducted MRI scans of newborns (mean age = 5 weeks) to determine cocaine's impact on early brain structural development. Subjects were three groups of infants: 33 with PCE co-morbid with other drugs, 46 drug-free controls and 40 with prenatal exposure to other drugs (nicotine, alcohol, marijuana, opiates, SSRIs) but without cocaine. Infants with PCE exhibited lesser total gray matter (GM) volume and greater total cerebral spinal fluid (CSF) volume compared with controls and infants with non-cocaine drug exposure. Analysis of regional volumes revealed that whole brain GM differences were driven primarily by lesser GM in prefrontal and frontal brain regions in infants with PCE, while more posterior regions (parietal, occipital) did not differ across groups. Greater CSF volumes in PCE infants were present in prefrontal, frontal and parietal but not occipital regions. Greatest differences (GM reduction, CSF enlargement) in PCE infants were observed in dorsal prefrontal cortex. Results suggest that PCE is associated with structural deficits in neonatal cortical gray matter, specifically in prefrontal and frontal regions involved in executive function and inhibitory control. Longitudinal study is required to determine whether these early differences persist and contribute to deficits in cognitive functions and enhanced risk for drug abuse seen at school age and in later life. Copyright © 2014 Elsevier Inc. All rights reserved.
Reversing the Real Brain Drain: Early Years Study--A Response.
ERIC Educational Resources Information Center
Killoran, Isabel
2001-01-01
Presents concerns over the "Early Years Study" (McCain & Mustard). Focuses on diversity issues related to the readiness measure used, parenting styles, and the importance of first language development. Questions the report's definition of "developmentally-attuned." Concludes by expressing hope that the Early Years Study…
Anomalous Development of Brain Structure and Function in Spina Bifida Myelomeningocele
ERIC Educational Resources Information Center
Juranek, Jenifer; Salman, Michael S.
2010-01-01
Spina bifida myelomeningocele (SBM) is a specific type of neural tube defect whereby the open neural tube at the level of the spinal cord alters brain development during early stages of gestation. Some structural anomalies are virtually unique to individuals with SBM, including a complex pattern of cerebellar dysplasia known as the Chiari II…
ERIC Educational Resources Information Center
Institute for Educational Leadership, Washington, DC.
This report presents the proceedings of a consortium at which leading developmental neuroscientists from across the United States and Canada met at Johns Hopkins University to explore the relationship between children's health and learning and to propose policy changes. Early brain development and its relationship to intelligence, learning, and…
Opendak, Maya; Sullivan, Regina M.
2016-01-01
Background Trauma has neurobehavioral effects when experienced at any stage of development, but trauma experienced in early life has unique neurobehavioral outcomes related to later life psychiatric sequelae. Recent evidence has further highlighted the context of infant trauma as a critical variable in determining its immediate and enduring consequences. Trauma experienced from an attachment figure, such as occurs in cases of caregiver child maltreatment, is particularly detrimental. Methods Using data primarily from rodent models, we review the literature on the interaction between trauma and attachment in early life, which highlights the role of the caregiver’s presence in engagement of attachment brain circuitry and suppressing threat processing by the amygdala. We then consider how trauma with and without the caregiver produces long-term changes in emotionality and behavior, and suggest that these experiences initiate distinct pathways to pathology. Results Together these data suggest that infant trauma processing and its enduring effects are impacted by both the immaturity of brain areas for processing trauma and the unique functioning of the early-life brain, which is biased toward processing information within the attachment circuitry. Conclusion An understanding of developmental differences in trauma processing as well as the critical role of the caregiver in further altering early life brain processing of trauma is important for developing age-relevant treatment and interventions. Highlights of this article Trauma experienced in early life has been linked with life-long outcomes for mental health through a mechanism that remains unclear. Trauma experienced in the presence of a caregiver has unique consequences. The infant brain is predisposed toward processing information using attachment circuitry rather than threat circuitry. Data from rodent models suggest that repeated trauma in the presence of a caregiver prematurely engages brain areas important for threat, which may play a role in deleterious outcome. PMID:27837581
Mechanical origins of rightward torsion in early chick brain development
NASA Astrophysics Data System (ADS)
Chen, Zi; Guo, Qiaohang; Dai, Eric; Taber, Larry
2015-03-01
During early development, the neural tube of the chick embryo undergoes a combination of progressive ventral bending and rightward torsion. This torsional deformation is one of the major organ-level left-right asymmetry events in development. Previous studies suggested that bending is mainly due to differential growth, however, the mechanism for torsion remains poorly understood. Since the heart almost always loops rightwards that the brain twists, researchers have speculated that heart looping affects the direction of brain torsion. However, direct evidence is lacking, nor is the mechanical origin of such torsion understood. In our study, experimental perturbations show that the bending and torsional deformations in the brain are coupled and that the vitelline membrane applies an external load necessary for torsion to occur. Moreover, the asymmetry of the looping heart gives rise to the chirality of the twisted brain. A computational model and a 3D printed physical model are employed to help interpret these findings. Our work clarifies the mechanical origins of brain torsion and the associated left-right asymmetry, and further reveals that the asymmetric development in one organ can induce the asymmetry of another developing organ through mechanics, reminiscent of D'Arcy Thompson's view of biological form as ``diagram of forces''. Z.C. is supported by the Society in Science - Branco Weiss fellowship, administered by ETH Zurich. L.A.T acknowledges the support from NIH Grants R01 GM075200 and R01 NS070918.
BRUMMELTE, S.; GLANAGHY, E. MC; BONNIN, A.; OBERLANDER, T. F.
2017-01-01
The neurotransmitter serotonin (5-HT) plays a central role in brain development, regulation of mood, stress reactivity and risk of psychiatric disorders, and thus alterations in 5-HT signaling early in life have critical implications for behavior and mental health across the life span. Drawing on preclinical and emerging human evidence this narrative review paper will examine three key aspects when considering the consequences of early life changes in 5-HT: (1) developmental origins of variations of 5-HT signaling; (2) influence of genetic and epigenetic factors; and (3) preclinical and clinical consequences of 5-HT-related changes associated with antidepressant exposure (SSRIs). The developmental consequences of altered prenatal 5-HT signaling varies greatly and outcomes depend on an ongoing interplay between biological (genetic/epigenetic variations) and environmental factors, both pre and postnatally. Emerging evidence suggests that variations in 5-HT signaling may increase sensitivity to risky home environments, but may also amplify a positive response to a nurturing environment. In this sense, factors that change central 5-HT levels may act as ‘plasticity’ rather than ‘risk’ factors associated with developmental vulnerability. Understanding the impact of early changes in 5-HT levels offers critical insights that might explain the variations in early typical brain development that underlies behavioral risk. PMID:26905950
ERIC Educational Resources Information Center
Shulman, Shanna
This 1997 Kids Count report examines challenges to Colorado children and youth and how prevention and early intervention can enhance their well-being. The report includes a summary of recent research on brain development and the importance of early experience and stimulation in early intervention programs. The levels of state funding for various…
Ma, Shang; Kwon, Hyo Jun; Huang, Zhen
2012-01-01
Astroglia are a major cell type in the brain and play a key role in many aspects of brain development and function. In the adult brain, astrocytes are known to intimately ensheath blood vessels and actively coordinate local neural activity and blood flow. During development of the neural retina, blood vessel growth follows a meshwork of astrocytic processes. Several genes have also been implicated in retinal astrocytes for regulating vessel development. This suggests a role of astrocytes in promoting angiogenesis throughout the central nervous system. To determine the roles that astrocytes may play during brain angiogenesis, we employ genetic approaches to inhibit astrogliogenesis during perinatal corticogenesis and examine its effects on brain vessel development. We find that conditional deletion from glial progenitors of orc3, a gene required for DNA replication, dramatically reduces glial progenitor cell number in the subventricular zone and astrocytes in the early postnatal cerebral cortex. This, in turn, results in severe reductions in both the density and branching frequency of cortical blood vessels. Consistent with a delayed growth but not regression of vessels, we find neither significant net decreases in vessel density between different stages after normalizing for cortical expansion nor obvious apoptosis of endothelial cells in these mutants. Furthermore, concomitant with loss of astroglial interactions, we find increased endothelial cell proliferation, enlarged vessel luminal size as well as enhanced cytoskeletal gene expression in pericytes, which suggests compensatory changes in vascular cells. Lastly, we find that blood vessel morphology in mutant cortices recovers substantially at later stages, following astrogliosis. These results thus implicate a functional requirement for astroglia in promoting blood vessel growth during brain development.
Hand in glove: brain and skull in development and dysmorphogenesis
Flaherty, Kevin
2013-01-01
The brain originates relatively early in development from differentiated ectoderm that forms a hollow tube and takes on an exceedingly complex shape with development. The skull is made up of individual bony elements that form from neural crest- and mesoderm-derived mesenchyme that unite to provide support and protection for soft tissues and spaces of the head. The meninges provide a protective and permeable membrane between brain and skull. Across evolutionary and developmental time, dynamic changes in brain and skull shape track one another so that their integration is evidenced in two structures that fit soundly regardless of changes in biomechanical and physiologic functions. Evidence for this tight correspondence is also seen in diseases of the craniofacial complex that are often classified as diseases of the skull (e.g., craniosynostosis) or diseases of the brain (e.g., holoprosencephaly) even when both tissues are affected. Our review suggests a model that links brain and skull morphogenesis through coordinated integration of signaling pathways (e.g., FGF, TGFβ, Wnt) via processes that are not currently understood, perhaps involving the meninges. Differences in the earliest signaling of biological structure establish divergent designs that will be enhanced during morphogenesis. Signaling systems that pattern the developing brain are also active in patterning required for growth and assembly of the skull and some members of these signaling families have been indicated as causal for craniofacial diseases. Because cells of early brain and skull are sensitive to similar signaling families, variation in the strength or timing of signals or shifts in patterning boundaries that affect one system (neural or skull) could also affect the other system and appropriate co-adjustments in development would be made. Interactions of these signaling systems and of the tissues that they pattern are fundamental to the consistent but labile functional and structural association of brain and skull conserved over evolutionary time obvious in the study of development and disease. PMID:23525521
Early Diagnosis and Early Intervention in Cerebral Palsy
Hadders-Algra, Mijna
2014-01-01
This paper reviews the opportunities and challenges for early diagnosis and early intervention in cerebral palsy (CP). CP describes a group of disorders of the development of movement and posture, causing activity limitation that is attributed to disturbances that occurred in the fetal or infant brain. Therefore, the paper starts with a summary of relevant information from developmental neuroscience. Most lesions underlying CP occur in the second half of gestation, when developmental activity in the brain reaches its summit. Variations in timing of the damage not only result in different lesions but also in different neuroplastic reactions and different associated neuropathologies. This turns CP into a heterogeneous entity. This may mean that the best early diagnostics and the best intervention methods may differ for various subgroups of children with CP. Next, the paper addresses possibilities for early diagnosis. It discusses the predictive value of neuromotor and neurological exams, neuroimaging techniques, and neurophysiological assessments. Prediction is best when complementary techniques are used in longitudinal series. Possibilities for early prediction of CP differ for infants admitted to neonatal intensive care and other infants. In the former group, best prediction is achieved with the combination of neuroimaging and the assessment of general movements, in the latter group, best prediction is based on carefully documented milestones and neurological assessment. The last part reviews early intervention in infants developing CP. Most knowledge on early intervention is based on studies in high-risk infants without CP. In these infants, early intervention programs promote cognitive development until preschool age; motor development profits less. The few studies on early intervention in infants developing CP suggest that programs that stimulate all aspects of infant development by means of family coaching are most promising. More research is urgently needed. PMID:25309506
Sukhinich, K K; Kosykh, A V; Aleksandrova, M A
2015-11-01
We studied the behavior and cell-cell interactions of embryonic brain cell from GFP-reporter mice after their transplantation into the intact adult brain. Fragments or cell suspensions of fetal neocortical cells at different stages of development were transplanted into the neocortex and striatum of adult recipients. Even in intact brain, the processes of transplanted neurons formed extensive networks in the striatum and neocortical layers I and V-VI. Processes of transplanted cells at different stages of development attained the rostral areas of the frontal cortex and some of them reached the internal capsule. However, the cells transplanted in suspension had lower process growth potency than cells from tissue fragments. Tyrosine hydroxylase fibers penetrated from the recipient brain into grafts at both early and late stages of development. Our experiments demonstrated the formation of extensive reciprocal networks between the transplanted fetal neural cells and recipient brain neurons even in intact brain.
1989-04-27
Narayan R, et al: Early insults to the injured brain. JAMA 240:439-442, 1978. 91 Neubauer JA, and Edelman N: Nonuniform brain blood flow response to...Research ( LAIR ), Bldg. 1110 ATI7I: SGRD-ULZ-RC Presidio of San Francisco, CA 94129-6815 1 copy Comander US Army Medical Research and Develop mnt Coand
Annual Research Review: The Promise of Stem Cell Research for Neuropsychiatric Disorders
ERIC Educational Resources Information Center
Vaccarino, Flora M.; Urban, Alexander Eckehart; Stevens, Hanna E.; Szekely, Anna; Abyzov, Alexej; Grigorenko, Elena L.; Gerstein, Mark; Weissman, Sherman
2011-01-01
The study of the developing brain has begun to shed light on the underpinnings of both early and adult onset neuropsychiatric disorders. Neuroimaging of the human brain across developmental time points and the use of model animal systems have combined to reveal brain systems and gene products that may play a role in autism spectrum disorders,…
ERIC Educational Resources Information Center
Luby, Joan; Rogers, Cynthia
2013-01-01
Advances in brain imaging methods and technology over the last 2 decades have opened an unprecedented window into the understanding of the structure and function of the human brain. In this article, the authors describe their investigation of the relationship between maternal support, observed during the preschool period, and the size of key brain…
Baroncelli, Laura; Cenni, Maria Cristina; Melani, Riccardo; Deidda, Gabriele; Landi, Silvia; Narducci, Roberta; Cancedda, Laura; Maffei, Lamberto; Berardi, Nicoletta
2017-02-01
Environmental enrichment (EE) has a remarkable impact on brain development. Continuous exposure to EE from birth determines a significant acceleration of visual system maturation both at retinal and cortical levels. A pre-weaning enriched experience is sufficient to trigger the accelerated maturation of the visual system, suggesting that factors affected by EE during the first days of life might prime visual circuits towards a faster development. The search for such factors is crucial not only to gain a better understanding of the molecular hierarchy of brain development but also to identify molecular pathways amenable to be targeted to correct atypical brain developmental trajectories. Here, we showed that IGF-1 levels are increased in the visual cortex of EE rats as early as P6 and this is a crucial event for setting in motion the developmental program induced by EE. Early intracerebroventricular (i.c.v.) infusion of IGF-1 in standard rats was sufficient to mimic the action of EE on visual acuity development, whereas blocking IGF-1 signaling by i.c.v. injections of the IGF-1 receptor antagonist JB1 prevented the deployment of EE effects. Early IGF-1 decreased the ratio between the expression of NKCC1 and KCC2 cation/chloride transporters, and the reversal potential for GABA A R-driven Cl - currents (E Cl ) was shifted toward more negative potentials, indicating that IGF-1 is a crucial factor in accelerating the maturation of GABAergic neurotransmission and promoting the developmental switch of GABA polarity from excitation to inhibition. In addition, early IGF-1 promoted a later occurring increase in its own expression, suggesting a priming effect of early IGF-1 in driving post-weaning cortical maturation. Copyright © 2016 Elsevier Ltd. All rights reserved.
Malinova, Vesna; Dolatowski, Karoline; Schramm, Peter; Moerer, Onnen; Rohde, Veit; Mielke, Dorothee
2016-07-01
OBJECT This prospective study investigated the role of whole-brain CT perfusion (CTP) studies in the identification of patients at risk for delayed ischemic neurological deficits (DIND) and of tissue at risk for delayed cerebral infarction (DCI). METHODS Forty-three patients with aneurysmal subarachnoid hemorrhage (aSAH) were included in this study. A CTP study was routinely performed in the early phase (Day 3). The CTP study was repeated in cases of transcranial Doppler sonography (TCD)-measured blood flow velocity (BFV) increase of > 50 cm/sec within 24 hours and/or on Day 7 in patients who were intubated/sedated. RESULTS Early CTP studies revealed perfusion deficits in 14 patients, of whom 10 patients (72%) developed DIND, and 6 of these 10 patients (60%) had DCI. Three of the 14 patients (21%) with early perfusion deficits developed DCI without having had DIND, and the remaining patient (7%) had neither DIND nor DCI. There was a statistically significant correlation between early perfusion deficits and occurrence of DIND and DCI (p < 0.0001). A repeated CTP was performed in 8 patients with a TCD-measured BFV increase > 50 cm/sec within 24 hours, revealing a perfusion deficit in 3 of them (38%). Two of the 3 patients (67%) developed DCI without preceding DIND and 1 patient (33%) had DIND without DCI. In 4 of the 7 patients (57%) who were sedated and/or comatose, additional CTP studies on Day 7 showed perfusion deficits. All 4 patients developed DCI. CONCLUSIONS Whole-brain CTP on Day 3 after aSAH allows early and reliable identification of patients at risk for DIND and tissue at risk for DCI. Additional CTP investigations, guided by TCD-measured BFV increase or persisting coma, do not contribute to information gain.
Developmental changes in the structure of the social brain in late childhood and adolescence.
Mills, Kathryn L; Lalonde, François; Clasen, Liv S; Giedd, Jay N; Blakemore, Sarah-Jayne
2014-01-01
Social cognition provides humans with the necessary skills to understand and interact with one another. One aspect of social cognition, mentalizing, is associated with a network of brain regions often referred to as the 'social brain.' These consist of medial prefrontal cortex [medial Brodmann Area 10 (mBA10)], temporoparietal junction (TPJ), posterior superior temporal sulcus (pSTS) and anterior temporal cortex (ATC). How these specific regions develop structurally across late childhood and adolescence is not well established. This study examined the structural developmental trajectories of social brain regions in the longest ongoing longitudinal neuroimaging study of human brain maturation. Structural trajectories of grey matter volume, cortical thickness and surface area were analyzed using surface-based cortical reconstruction software and mixed modeling in a longitudinal sample of 288 participants (ages 7-30 years, 857 total scans). Grey matter volume and cortical thickness in mBA10, TPJ and pSTS decreased from childhood into the early twenties. The ATC increased in grey matter volume until adolescence and in cortical thickness until early adulthood. Surface area for each region followed a cubic trajectory, peaking in early or pre-adolescence before decreasing into the early twenties. These results are discussed in the context of developmental changes in social cognition across adolescence.
Early functional and morphological brain disturbances in late-onset intrauterine growth restriction.
Starčević, Mirta; Predojević, Maja; Butorac, Dražan; Tumbri, Jasna; Konjevoda, Paško; Kadić, Aida Salihagić
2016-02-01
To determine whether the brain disturbances develop in late-onset intrauterine growth restriction (IUGR) before blood flow redistribution towards the fetal brain (detected by Doppler measurements in the middle cerebral artery and umbilical artery). Further, to evaluate predictive values of Doppler arterial indices and umbilical cord blood gases and pH for early functional and/or morphological brain disturbances in late-onset IUGR. This cohort study included 60 singleton term pregnancies with placental insufficiency caused late-onset IUGR (IUGR occurring after 34 gestational weeks). Umbilical artery resistance index (URI), middle cerebral artery resistance index (CRI), and cerebroumbilical (C/U) ratio (CRI/URI) were monitored once weekly. Umbilical blood cord samples (arterial and venous) were collected for the analysis of pO2, pCO2 and pH. Morphological neurological outcome was evaluated by cranial ultrasound (cUS), whereas functional neurological outcome by Amiel-Tison Neurological Assessment at Term (ATNAT). 50 fetuses had C/U ratio>1, and 10 had C/U ratio≤1; among these 10 fetuses, 9 had abnormal neonatal cUS findings and all 10 had non-optimal ATNAT. However, the total number of abnormal neurological findings was much higher. 32 neonates had abnormal cUS (53.37%), and 42 (70.00%) had non-optimal ATNAT. Furthermore, Doppler indices had higher predictive validity for early brain disturbances than umbilical cord blood gases and pH. C/U ratio had the highest predictive validity with threshold for adverse neurological outcome at value 1.13 (ROC analysis), i.e., 1.18 (party machine learning algorithm). Adverse neurological outcome at average values of C/U ratios>1 confirmed that early functional and/or structural brain disturbances in late-onset IUGR develop even before activation of fetal cardiovascular compensatory mechanisms, i.e., before Doppler signs of blood flow redistribution between the fetal brain and the placenta. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Karolis, Vyacheslav R.; Froudist-Walsh, Sean; Brittain, Philip J.; Kroll, Jasmin; Ball, Gareth; Edwards, A. David; Dell'Acqua, Flavio; Williams, Steven C.; Murray, Robin M.; Nosarti, Chiara
2016-01-01
The second half of pregnancy is a crucial period for the development of structural brain connectivity, and an abrupt interruption of the typical processes of development during this phase caused by the very preterm birth (<33 weeks of gestation) is likely to result in long-lasting consequences. We used structural and diffusion imaging data to reconstruct the brain structural connectome in very preterm-born adults. We assessed its rich-club organization and modularity as 2 characteristics reflecting the capacity to support global and local information exchange, respectively. Our results suggest that the establishment of global connectivity patterns is prioritized over peripheral connectivity following early neurodevelopmental disruption. The very preterm brain exhibited a stronger rich-club architecture than the control brain, despite possessing a relative paucity of white matter resources. Using a simulated lesion approach, we also investigated whether putative structural reorganization takes place in the very preterm brain in order to compensate for its anatomical constraints. We found that connections between the basal ganglia and (pre-) motor regions, as well as connections between subcortical regions, assumed an altered role in the structural connectivity of the very preterm brain, and that such alterations had functional implications for information flow, rule learning, and verbal IQ. PMID:26742566
Mother-infant interactions and regional brain volumes in infancy: an MRI study.
Sethna, Vaheshta; Pote, Inês; Wang, Siying; Gudbrandsen, Maria; Blasi, Anna; McCusker, Caroline; Daly, Eileen; Perry, Emily; Adams, Kerrie P H; Kuklisova-Murgasova, Maria; Busuulwa, Paula; Lloyd-Fox, Sarah; Murray, Lynne; Johnson, Mark H; Williams, Steven C R; Murphy, Declan G M; Craig, Michael C; McAlonan, Grainne M
2017-07-01
It is generally agreed that the human brain is responsive to environmental influences, and that the male brain may be particularly sensitive to early adversity. However, this is largely based on retrospective studies of older children and adolescents exposed to extreme environments in childhood. Less is understood about how normative variations in parent-child interactions are associated with the development of the infant brain in typical settings. To address this, we used magnetic resonance imaging to investigate the relationship between observational measures of mother-infant interactions and regional brain volumes in a community sample of 3- to 6-month-old infants (N = 39). In addition, we examined whether this relationship differed in male and female infants. We found that lower maternal sensitivity was correlated with smaller subcortical grey matter volumes in the whole sample, and that this was similar in both sexes. However, male infants who showed greater levels of positive communication and engagement during early interactions had smaller cerebellar volumes. These preliminary findings suggest that variations in mother-infant interaction dimensions are associated with differences in infant brain development. Although the study is cross-sectional and causation cannot be inferred, the findings reveal a dynamic interaction between brain and environment that may be important when considering interventions to optimize infant outcomes.
Developmental Changes in Organization of Structural Brain Networks
Khundrakpam, Budhachandra S.; Reid, Andrew; Brauer, Jens; Carbonell, Felix; Lewis, John; Ameis, Stephanie; Karama, Sherif; Lee, Junki; Chen, Zhang; Das, Samir; Evans, Alan C.; Ball, William S.; Byars, Anna Weber; Schapiro, Mark; Bommer, Wendy; Carr, April; German, April; Dunn, Scott; Rivkin, Michael J.; Waber, Deborah; Mulkern, Robert; Vajapeyam, Sridhar; Chiverton, Abigail; Davis, Peter; Koo, Julie; Marmor, Jacki; Mrakotsky, Christine; Robertson, Richard; McAnulty, Gloria; Brandt, Michael E.; Fletcher, Jack M.; Kramer, Larry A.; Yang, Grace; McCormack, Cara; Hebert, Kathleen M.; Volero, Hilda; Botteron, Kelly; McKinstry, Robert C.; Warren, William; Nishino, Tomoyuki; Robert Almli, C.; Todd, Richard; Constantino, John; McCracken, James T.; Levitt, Jennifer; Alger, Jeffrey; O'Neil, Joseph; Toga, Arthur; Asarnow, Robert; Fadale, David; Heinichen, Laura; Ireland, Cedric; Wang, Dah-Jyuu; Moss, Edward; Zimmerman, Robert A.; Bintliff, Brooke; Bradford, Ruth; Newman, Janice; Evans, Alan C.; Arnaoutelis, Rozalia; Bruce Pike, G.; Louis Collins, D.; Leonard, Gabriel; Paus, Tomas; Zijdenbos, Alex; Das, Samir; Fonov, Vladimir; Fu, Luke; Harlap, Jonathan; Leppert, Ilana; Milovan, Denise; Vins, Dario; Zeffiro, Thomas; Van Meter, John; Lange, Nicholas; Froimowitz, Michael P.; Botteron, Kelly; Robert Almli, C.; Rainey, Cheryl; Henderson, Stan; Nishino, Tomoyuki; Warren, William; Edwards, Jennifer L.; Dubois, Diane; Smith, Karla; Singer, Tish; Wilber, Aaron A.; Pierpaoli, Carlo; Basser, Peter J.; Chang, Lin-Ching; Koay, Chen Guan; Walker, Lindsay; Freund, Lisa; Rumsey, Judith; Baskir, Lauren; Stanford, Laurence; Sirocco, Karen; Gwinn-Hardy, Katrina; Spinella, Giovanna; McCracken, James T.; Alger, Jeffry R.; Levitt, Jennifer; O'Neill, Joseph
2013-01-01
Recent findings from developmental neuroimaging studies suggest that the enhancement of cognitive processes during development may be the result of a fine-tuning of the structural and functional organization of brain with maturation. However, the details regarding the developmental trajectory of large-scale structural brain networks are not yet understood. Here, we used graph theory to examine developmental changes in the organization of structural brain networks in 203 normally growing children and adolescents. Structural brain networks were constructed using interregional correlations in cortical thickness for 4 age groups (early childhood: 4.8–8.4 year; late childhood: 8.5–11.3 year; early adolescence: 11.4–14.7 year; late adolescence: 14.8–18.3 year). Late childhood showed prominent changes in topological properties, specifically a significant reduction in local efficiency, modularity, and increased global efficiency, suggesting a shift of topological organization toward a more random configuration. An increase in number and span of distribution of connector hubs was found in this age group. Finally, inter-regional connectivity analysis and graph-theoretic measures indicated early maturation of primary sensorimotor regions and protracted development of higher order association and paralimbic regions. Our finding reveals a time window of plasticity occurring during late childhood which may accommodate crucial changes during puberty and the new developmental tasks that an adolescent faces. PMID:22784607
A novel framework for the local extraction of extra-axial cerebrospinal fluid from MR brain images
NASA Astrophysics Data System (ADS)
Mostapha, Mahmoud; Shen, Mark D.; Kim, SunHyung; Swanson, Meghan; Collins, D. Louis; Fonov, Vladimir; Gerig, Guido; Piven, Joseph; Styner, Martin A.
2018-03-01
The quantification of cerebrospinal fluid (CSF) in the human brain has shown to play an important role in early postnatal brain developmental. Extr a-axial fluid (EA-CSF), which is characterized by the CSF in the subarachnoid space, is promising in the early detection of children at risk for neurodevelopmental disorders. Currently, though, there is no tool to extract local EA-CSF measurements in a way that is suitable for localized analysis. In this paper, we propose a novel framework for the localized, cortical surface based analysis of EA-CSF. In our proposed processing, we combine probabilistic brain tissue segmentation, cortical surface reconstruction as well as streamline based local EA-CSF quantification. For streamline computation, we employ the vector field generated by solving a Laplacian partial differential equation (PDE) between the cortical surface and the outer CSF hull. To achieve sub-voxel accuracy while minimizing numerical errors, fourth-order Runge-Kutta (RK4) integration was used to generate the streamlines. Finally, the local EA-CSF is computed by integrating the CSF probability along the generated streamlines. The proposed local EA-CSF extraction tool was used to study the early postnatal brain development in typically developing infants. The results show that the proposed localized EA-CSF extraction pipeline can produce statistically significant regions that are not observed in previous global approach.
Gut microbiota depletion from early adolescence in mice: Implications for brain and behaviour.
Desbonnet, Lieve; Clarke, Gerard; Traplin, Alexander; O'Sullivan, Orla; Crispie, Fiona; Moloney, Rachel D; Cotter, Paul D; Dinan, Timothy G; Cryan, John F
2015-08-01
There is growing appreciation for the importance of bacteria in shaping brain development and behaviour. Adolescence and early adulthood are crucial developmental periods during which exposure to harmful environmental factors can have a permanent impact on brain function. Such environmental factors include perturbations of the gut bacteria that may affect gut-brain communication, altering the trajectory of brain development, and increasing vulnerability to psychiatric disorders. Here we assess the effects of gut bacterial depletion from weaning onwards on adult cognitive, social and emotional behaviours and markers of gut-brain axis dysfunction in mice. Mice were treated with a combination of antibiotics from weaning onwards and effects on behaviours and potential gut-brain axis neuromodulators (tryptophan, monoamines, and neuropeptides) and BDNF expression were assessed in adulthood. Antibiotic-treatment depleted and restructured gut microbiota composition of caecal contents and decreased spleen weights in adulthood. Depletion of the gut microbiota from weaning onwards reduced anxiety, induced cognitive deficits, altered dynamics of the tryptophan metabolic pathway, and significantly reduced BDNF, oxytocin and vasopressin expression in the adult brain. Microbiota depletion from weaning onwards by means of chronic treatment with antibiotics in mice impacts on anxiety and cognitive behaviours as well as key neuromodulators of gut-brain communication in a manner that is similar to that reported in germ-free mice. This model may represent a more amenable alternative for germ-free mice in the assessment of microbiota modulation of behaviour. Finally, these data suggest that despite the presence of a normal gut microbiome in early postnatal life, reduced abundance and diversity of the gut microbiota from weaning influences adult behaviours and key neuromodulators of the microbiota-gut-brain axis suggesting that dysregulation of this axis in the post-weaning period may contribute to the pathogenesis of disorders associated with altered anxiety and cognition. Copyright © 2015 Elsevier Inc. All rights reserved.
Influence of maternal thyroid hormones during gestation on fetal brain development
Moog, Nora K.; Entringer, Sonja; Heim, Christine; Wadhwa, Pathik D.; Kathmann, Norbert; Buss, Claudia
2015-01-01
Thyroid hormones (TH) play an obligatory role in many fundamental processes underlying brain development and maturation. The developing embryo/fetus is dependent on maternal supply of TH. The fetal thyroid gland does not commence THs synthesis until mid gestation, and the adverse consequences of severe maternal TH deficiency on offspring neurodevelopment are well established. Recent evidence suggests that even more moderate forms of maternal thyroid dysfunction, particularly during early gestation, may have a long-lasting influence on child cognitive development and risk of neurodevelopmental disorders. Moreover, these observed alterations appear to be largely irreversible after birth. It is, therefore, important to gain a better understanding of the role of maternal thyroid dysfunction on offspring neurodevelopment in terms of the nature, magnitude, time-specificity, and context-specificity of its effects. With respect to the issue of context specificity, it is possible that maternal stress and stress-related biological processes during pregnancy may modulate maternal thyroid function. The possibility of an interaction between the thyroid and stress systems in the context of fetal brain development has, however, not been addressed to date. We begin this review with a brief overview of TH biology during pregnancy and a summary of the literature on its effect on the developing brain. Next, we consider and discuss whether and how processes related to maternal stress and stress biology may interact with and modify the effects of maternal thyroid function on offspring brain development. We synthesize several research areas and identify important knowledge gaps that may warrant further study. The scientific and public health relevance of this review relates to achieving a better understanding of the timing, mechanisms and contexts of thyroid programming of brain development, with implications for early identification of risk, primary prevention and intervention. PMID:26434624
Doing What Doesn't Come Naturally: The Development of Self-Regulation
ERIC Educational Resources Information Center
Thompson, Ross A.
2009-01-01
Self-regulatory limitations are typical of young children, whose impulsiveness, distractibility, and emotional outbursts can amuse and frustrate parents and practitioners. During the last 30 years, however, research into the development of self-regulation has revealed that early childhood is a very early stage in the maturation of brain regions…
Arnoldussen, Ilse A C; Zerbi, Valerio; Wiesmann, Maximilian; Noordman, Rikko H J; Bolijn, Simone; Mutsaers, Martina P C; Dederen, Pieter J W C; Kleemann, Robert; Kooistra, Teake; van Tol, Eric A F; Gross, Gabriele; Schoemaker, Marieke H; Heerschap, Arend; Wielinga, Peter Y; Kiliaan, Amanda J
2016-04-01
Worldwide, the incidence of obesity is increasing at an alarming rate, and the number of children with obesity is especially worrisome. These developments raise concerns about the physical, psychosocial and cognitive consequences of obesity. It was shown that early dietary intake of arachidonic acid (ARA) and docosahexaenoic acid (DHA) can reduce the detrimental effects of later obesogenic feeding on lipid metabolism and adipogenesis in an animal model of mild obesity. In the present study, the effects of early dietary ARA and DHA on cognition and brain structure were examined in mildly obesogenic ApoE*3Leiden mouse model. We used cognitive tests and neuroimaging during early and later life. During their early development after weaning (4-13weeks of age), mice were fed a chow diet or ARA and DHA diet for 8 weeks and then switched to a high-fat and high-carbohydrate (HFHC) diet for 12weeks (14-26weeks of age). An HFHC-diet led to increased energy storage in white adipose tissue, increased cholesterol levels, decreased triglycerides levels, increased cerebral blood flow and decreased functional connectivity between brain regions as well as cerebrovascular and gray matter integrity. ARA and DHA intake reduced the HFHC-diet-induced increase in body weight, attenuated plasma triglycerides levels and improved cerebrovasculature, gray matter integrity and functional connectivity in later life. In conclusion, an HFHC diet causes adverse structural brain and metabolic adaptations, most of which can be averted by dietary ARA and DHA intake early in life supporting metabolic flexibility and cerebral integrity later in life. Copyright © 2016 Elsevier Inc. All rights reserved.
ERIC Educational Resources Information Center
Sohlberg, McKay Moore; Kucheria, Priya; Fickas, Stephen; Wade, Shari L.
2015-01-01
Purpose: The purpose of this research article is to describe two very different lines of brain injury treatment research, both of which illuminate the benefits of implementation science. Method: The article first describes the development and pilot of a computerized cognitive intervention and highlights how adherence to implementation science…
Dinstein, Ilan; Haar, Shlomi; Atsmon, Shir; Schtaerman, Hen
2017-01-01
Large controversy exists regarding the potential existence and clinical significance of larger brain volumes in toddlers who later develop autism. Assessing this relationship is important for determining the clinical utility of early head circumference (HC) measures and for assessing the validity of the early overgrowth hypothesis of autism, which suggests that early accelerated brain development may be a hallmark of the disorder. We performed a retrospective comparison of HC, height, and weight measurements between 66 toddlers who were later diagnosed with autism and 66 matched controls. These toddlers represent an unbiased regional sample from a single health service provider in the southern district of Israel. On average, participating toddlers had >8 measurements between birth and the age of two, which enabled us to characterize individual HC, height, and weight development with high precision and fit a negative exponential growth model to the data of each toddler with exceptional accuracy. The analyses revealed that HC sizes and growth rates were not significantly larger in toddlers with autism even when stratifying the autism group based on verbal capabilities at the time of diagnosis. In addition, there were no significant correlations between ADOS scores at the time of diagnosis and HC at any time-point during the first 2 years of life. These negative results add to accumulating evidence, which suggest that brain volume is not necessarily larger in toddlers who develop autism. We believe that conflicting results reported in other studies are due to small sample sizes, use of misleading population norms, changes in the clinical definition of autism over time, and/or inclusion of individuals with syndromic autism. While abnormally large brains may be evident in some individuals with autism and more clearly visible in MRI scans, converging evidence from this and other studies suggests that enlarged HC is not a common etiology of the entire autism population. Early HC measures, therefore, offer very limited clinical utility for assessment of autism risk in the general population.
Play-Based Neuropsychological Assessment of Toddlers
ERIC Educational Resources Information Center
Dykeman, Bruce F.
2008-01-01
Standardized psychological assessment provides a precise yet limited view of the neuropsychological status of preschool toddlers, whose brain functioning is only beginning to develop localized functioning. Yet, referrals for preschool evaluation of these early-age children often request a wide variety of information about brain-behavior…
Pavlova, Marina A; Krägeloh-Mann, Ingeborg
2013-04-01
Brain lesions to the white matter in peritrigonal regions, periventricular leukomalacia, in children who were born prematurely represent an important model for studying limitations on brain development. The lesional pattern is of early origin and bilateral, that constrains the compensatory potential of the brain. We suggest that (i) topography and severity of periventricular lesions may have a long-term predictive value for cognitive and social capabilities in preterm birth survivors; and (ii) periventricular lesions may impact cognitive and social functions by affecting brain connectivity, and thereby, the dissociable neural networks underpinning these functions. A further pathway to explore is the relationship between cerebral palsy and cognitive outcome. Restrictions caused by motor disability may affect active exploration of surrounding and social participation that may in turn differentially impinge on cognitive development and social cognition. As an outline for future research, we underscore sex differences, as the sex of a preterm newborn may shape the mechanisms by which the developing brain is affected.
Bilingualism Alters Children's Frontal Lobe Functioning for Attentional Control
Arredondo, Maria M.; Hu, Xiao-Su; Satterfield, Teresa; Kovelman, Ioulia
2017-01-01
Bilingualism is a typical linguistic experience, yet relatively little is known about its impact on children's cognitive and brain development. Theories of bilingualism suggest early dual-language acquisition can improve children's cognitive abilities, specifically those relying on frontal lobe functioning. While behavioral findings present much conflicting evidence, little is known about its effects on children's frontal lobe development. Using functional Near-Infrared Spectroscopy (fNIRS), the findings suggest that Spanish-English bilingual children (n=13, ages 7-13) had greater activation in left prefrontal cortex during a non-verbal attentional control task relative to age-matched English monolinguals. In contrast, monolinguals (n=14) showed greater right prefrontal activation than bilinguals. The present findings suggest early bilingualism yields significant changes to the functional organization of children's prefrontal cortex for attentional control and carry implications for understanding how early life experiences impact cognition and brain development. PMID:26743118
Shen, Mark D; Nordahl, Christine W; Young, Gregory S; Wootton-Gorges, Sandra L; Lee, Aaron; Liston, Sarah E; Harrington, Kayla R; Ozonoff, Sally; Amaral, David G
2013-09-01
Prospective studies of infants at risk for autism spectrum disorder have provided important clues about the early behavioural symptoms of autism spectrum disorder. Diagnosis of autism spectrum disorder, however, is not currently made until at least 18 months of age. There is substantially less research on potential brain-based differences in the period between 6 and 12 months of age. Our objective in the current study was to use magnetic resonance imaging to identify any consistently observable brain anomalies in 6-9 month old infants who would later develop autism spectrum disorder. We conducted a prospective infant sibling study with longitudinal magnetic resonance imaging scans at three time points (6-9, 12-15, and 18-24 months of age), in conjunction with intensive behavioural assessments. Fifty-five infants (33 'high-risk' infants having an older sibling with autism spectrum disorder and 22 'low-risk' infants having no relatives with autism spectrum disorder) were imaged at 6-9 months; 43 of these (27 high-risk and 16 low-risk) were imaged at 12-15 months; and 42 (26 high-risk and 16 low-risk) were imaged again at 18-24 months. Infants were classified as meeting criteria for autism spectrum disorder, other developmental delays, or typical development at 24 months or later (mean age at outcome: 32.5 months). Compared with the other two groups, infants who developed autism spectrum disorder (n = 10) had significantly greater extra-axial fluid at 6-9 months, which persisted and remained elevated at 12-15 and 18-24 months. Extra-axial fluid is characterized by excessive cerebrospinal fluid in the subarachnoid space, particularly over the frontal lobes. The amount of extra-axial fluid detected as early as 6 months was predictive of more severe autism spectrum disorder symptoms at the time of outcome. Infants who developed autism spectrum disorder also had significantly larger total cerebral volumes at both 12-15 and 18-24 months of age. This is the first magnetic resonance imaging study to prospectively evaluate brain growth trajectories from infancy in children who develop autism spectrum disorder. The presence of excessive extra-axial fluid detected as early as 6 months and the lack of resolution by 24 months is a hitherto unreported brain anomaly in infants who later develop autism spectrum disorder. This is also the first magnetic resonance imaging evidence of brain enlargement in autism before age 2. These findings raise the potential for the use of structural magnetic resonance imaging to aid in the early detection of children at risk for autism spectrum disorder or other neurodevelopmental disorders.
Fragmentation and Unpredictability of Early-Life Experience in Mental Disorders
Baram, Tallie Z.; Solodkin, Ana; Davis, Elysia P.; Stern, Hal; Obenaus, Andre; Sandman, Curt A.; Small, Steven L.
2012-01-01
Maternal sensory signals in early life play a crucial role in programming the structure and function of the developing brain, promoting vulnerability or resilience to emotional and cognitive disorders. In rodent models of early-life stress, fragmentation and unpredictability of maternally derived sensory signals provoke persistent cognitive and emotional dysfunction in offspring. Similar variability and inconsistency of maternal signals during both gestation and early postnatal human life may influence development of emotional and cognitive functions, including those that underlie later depression and anxiety. PMID:22885631
Normative brain size variation and brain shape diversity in humans.
Reardon, P K; Seidlitz, Jakob; Vandekar, Simon; Liu, Siyuan; Patel, Raihaan; Park, Min Tae M; Alexander-Bloch, Aaron; Clasen, Liv S; Blumenthal, Jonathan D; Lalonde, Francois M; Giedd, Jay N; Gur, Ruben C; Gur, Raquel E; Lerch, Jason P; Chakravarty, M Mallar; Satterthwaite, Theodore D; Shinohara, Russell T; Raznahan, Armin
2018-06-15
Brain size variation over primate evolution and human development is associated with shifts in the proportions of different brain regions. Individual brain size can vary almost twofold among typically developing humans, but the consequences of this for brain organization remain poorly understood. Using in vivo neuroimaging data from more than 3000 individuals, we find that larger human brains show greater areal expansion in distributed frontoparietal cortical networks and related subcortical regions than in limbic, sensory, and motor systems. This areal redistribution recapitulates cortical remodeling across evolution, manifests by early childhood in humans, and is linked to multiple markers of heightened metabolic cost and neuronal connectivity. Thus, human brain shape is systematically coupled to naturally occurring variations in brain size through a scaling map that integrates spatiotemporally diverse aspects of neurobiology. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
Neurodevelopmental origins of lifespan changes in brain and cognition.
Walhovd, Kristine B; Krogsrud, Stine K; Amlien, Inge K; Bartsch, Hauke; Bjørnerud, Atle; Due-Tønnessen, Paulina; Grydeland, Håkon; Hagler, Donald J; Håberg, Asta K; Kremen, William S; Ferschmann, Lia; Nyberg, Lars; Panizzon, Matthew S; Rohani, Darius A; Skranes, Jon; Storsve, Andreas B; Sølsnes, Anne Elisabeth; Tamnes, Christian K; Thompson, Wesley K; Reuter, Chase; Dale, Anders M; Fjell, Anders M
2016-08-16
Neurodevelopmental origins of functional variation in older age are increasingly being acknowledged, but identification of how early factors impact human brain and cognition throughout life has remained challenging. Much focus has been on age-specific mechanisms affecting neural foundations of cognition and their change. In contrast to this approach, we tested whether cerebral correlates of general cognitive ability (GCA) in development could be extended to the rest of the lifespan, and whether early factors traceable to prenatal stages, such as birth weight and parental education, may exert continuous influences. We measured the area of the cerebral cortex in a longitudinal sample of 974 individuals aged 4-88 y (1,633 observations). An extensive cortical region was identified wherein area related positively to GCA in development. By tracking area of the cortical region identified in the child sample throughout the lifespan, we showed that the cortical change trajectories of higher and lower GCA groups were parallel through life, suggesting continued influences of early life factors. Birth weight and parental education obtained from the Norwegian Mother-Child Cohort study were identified as such early factors of possible life-long influence. Support for a genetic component was obtained in a separate twin sample (Vietnam Era Twin Study of Aging), but birth weight in the child sample had an effect on cortical area also when controlling for possible genetic differences in terms of parental height. Our results provide novel evidence for stability in brain-cognition relationships throughout life, and indicate that early life factors impact brain and cognition for the entire life course.
Zhan, L.; Liu, Y.; Zhou, J.; Ye, J.; Thompson, P.M.
2015-01-01
Mild cognitive impairment (MCI) is an intermediate stage between normal aging and Alzheimer's disease (AD), and around 10-15% of people with MCI develop AD each year. More recently, MCI has been further subdivided into early and late stages, and there is interest in identifying sensitive brain imaging biomarkers that help to differentiate stages of MCI. Here, we focused on anatomical brain networks computed from diffusion MRI and proposed a new feature extraction and classification framework based on higher order singular value decomposition and sparse logistic regression. In tests on publicly available data from the Alzheimer's Disease Neuroimaging Initiative, our proposed framework showed promise in detecting brain network differences that help in classifying early versus late MCI. PMID:26413202
The right brain is dominant in psychotherapy.
Schore, Allan N
2014-09-01
This article discusses how recent studies of the right brain, which is dominant for the implicit, nonverbal, intuitive, holistic processing of emotional information and social interactions, can elucidate the neurobiological mechanisms that underlie the relational foundations of psychotherapy. Utilizing the interpersonal neurobiological perspective of regulation theory, I describe the fundamental role of the early developing right brain in relational processes, throughout the life span. I present interdisciplinary evidence documenting right brain functions in early attachment processes, in emotional communications within the therapeutic alliance, in mutual therapeutic enactments, and in therapeutic change processes. This work highlights the fact that the current emphasis on relational processes is shared by, cross-fertilizing, and indeed transforming both psychology and neuroscience, with important consequences for clinical psychological models of psychotherapeutic change. PsycINFO Database Record (c) 2014 APA, all rights reserved.
Sauer, Roland; Gölitz, Philipp; Jacobi, Johannes; Schwab, Stefan; Linker, Ralf A; Lee, De-Hyung
2017-04-15
Progressive multifocal leukoencephalopathy (PML) is a rare, opportunistic and often fatal disease of the CNS which may occur under immunosuppression in transplant patients. Brain stem PML is associated with a particularly bad prognosis. Here, we present a case of a renal transplant patient treated with mycophenolate mofetil (MMF) and tacrolimus who developed brain stem PML with limb ataxia, dysarthria and dysphagia. Diagnosis was established by typical MRI features and detection of JCV-DNA in the CSF. Immune reconstitution after stopping MMF and tacrolimus led to a complete and sustained remission of symptoms with improvement of the brain stem lesion over a follow-up over 20months. In summary, early detection of PML and consequent treatment may improve neurological outcomes even in brain stem disease with a notorious bad prognosis. Copyright © 2017 Elsevier B.V. All rights reserved.
ERIC Educational Resources Information Center
Knitzer, Jane; Lefkowitz, Jill
2006-01-01
Compelling evidence from neuroscience about how early relationships and experience influence the architecture of the brain, and in turn early school success, has led to increasing policy and practice attention to implementing child development and family support programs like Early Head Start for infants and toddlers. But, there is also a group of…
Joint Attention and Brain Functional Connectivity in Infants and Toddlers.
Eggebrecht, Adam T; Elison, Jed T; Feczko, Eric; Todorov, Alexandre; Wolff, Jason J; Kandala, Sridhar; Adams, Chloe M; Snyder, Abraham Z; Lewis, John D; Estes, Annette M; Zwaigenbaum, Lonnie; Botteron, Kelly N; McKinstry, Robert C; Constantino, John N; Evans, Alan; Hazlett, Heather C; Dager, Stephen; Paterson, Sarah J; Schultz, Robert T; Styner, Martin A; Gerig, Guido; Das, Samir; Kostopoulos, Penelope; Schlaggar, Bradley L; Petersen, Steven E; Piven, Joseph; Pruett, John R
2017-03-01
Initiating joint attention (IJA), the behavioral instigation of coordinated focus of 2 people on an object, emerges over the first 2 years of life and supports social-communicative functioning related to the healthy development of aspects of language, empathy, and theory of mind. Deficits in IJA provide strong early indicators for autism spectrum disorder, and therapies targeting joint attention have shown tremendous promise. However, the brain systems underlying IJA in early childhood are poorly understood, due in part to significant methodological challenges in imaging localized brain function that supports social behaviors during the first 2 years of life. Herein, we show that the functional organization of the brain is intimately related to the emergence of IJA using functional connectivity magnetic resonance imaging and dimensional behavioral assessments in a large semilongitudinal cohort of infants and toddlers. In particular, though functional connections spanning the brain are involved in IJA, the strongest brain-behavior associations cluster within connections between a small subset of functional brain networks; namely between the visual network and dorsal attention network and between the visual network and posterior cingulate aspects of the default mode network. These observations mark the earliest known description of how functional brain systems underlie a burgeoning fundamental social behavior, may help improve the design of targeted therapies for neurodevelopmental disorders, and, more generally, elucidate physiological mechanisms essential to healthy social behavior development. © The Author 2017. Published by Oxford University Press.
Joint Attention and Brain Functional Connectivity in Infants and Toddlers
Eggebrecht, Adam T.; Elison, Jed T.; Feczko, Eric; Todorov, Alexandre; Wolff, Jason J.; Kandala, Sridhar; Adams, Chloe M.; Snyder, Abraham Z.; Lewis, John D.; Estes, Annette M.; Zwaigenbaum, Lonnie; Botteron, Kelly N.; McKinstry, Robert C.; Constantino, John N.; Evans, Alan; Hazlett, Heather C.; Dager, Stephen; Paterson, Sarah J.; Schultz, Robert T.; Styner, Martin A.; Gerig, Guido; Das, Samir; Kostopoulos, Penelope; Schlaggar, Bradley L.; Petersen, Steven E.; Piven, Joseph; Pruett, John R.
2017-01-01
Abstract Initiating joint attention (IJA), the behavioral instigation of coordinated focus of 2 people on an object, emerges over the first 2 years of life and supports social-communicative functioning related to the healthy development of aspects of language, empathy, and theory of mind. Deficits in IJA provide strong early indicators for autism spectrum disorder, and therapies targeting joint attention have shown tremendous promise. However, the brain systems underlying IJA in early childhood are poorly understood, due in part to significant methodological challenges in imaging localized brain function that supports social behaviors during the first 2 years of life. Herein, we show that the functional organization of the brain is intimately related to the emergence of IJA using functional connectivity magnetic resonance imaging and dimensional behavioral assessments in a large semilongitudinal cohort of infants and toddlers. In particular, though functional connections spanning the brain are involved in IJA, the strongest brain-behavior associations cluster within connections between a small subset of functional brain networks; namely between the visual network and dorsal attention network and between the visual network and posterior cingulate aspects of the default mode network. These observations mark the earliest known description of how functional brain systems underlie a burgeoning fundamental social behavior, may help improve the design of targeted therapies for neurodevelopmental disorders, and, more generally, elucidate physiological mechanisms essential to healthy social behavior development. PMID:28062515
The intersection of stress, drug abuse and development.
Thadani, Pushpa V
2002-01-01
Use or abuse of licit and illicit substances is often associated with environmental stress. Current clinical evidence clearly demonstrates neurobehavioral, somatic growth and developmental deficits in children born to drug-using mothers. However, the effects of environmental stress and its interaction with prenatal drug exposure on a child's development is unknown. Studies in pregnant animals under controlled conditions show drug-induced long-term alterations in brain structures and functions of the offspring. These cytoarchitecture alterations in the brain are often associated with perturbations in neurotransmitter systems that are intimately involved in the regulation of the stress responses. Similar abnormalities have been observed in the brains of animals exposed to other adverse exogenous (e.g., environmental stress) and/or endogenous (e.g., glucocorticoids) experiences during early life. The goal of this article is to: (1) provide evidence and a perspective that common neural systems are influenced during development both by perinatal drug exposure and early stress exposure; and (2) identify gaps and encourage new research examining the effects of early stress and perinatal drug exposure, in animal models, that would elucidate how stress- and drug-induced perturbations in neural systems influence later vulnerability to abused drugs in adult offspring.
Grover, V P B; Southern, L; Dyson, J K; Kim, J U; Crossey, M M E; Wylezinska-Arridge, M; Patel, N; Fitzpatrick, J A; Bak-Bol, A; Waldman, A D; Alexander, G J; Mells, G F; Chapman, R W; Jones, D E J; Taylor-Robinson, S D
2016-11-01
Brain change can occur in primary biliary cholangitis (PBC), potentially as a result of cholestatic and/or inflammatory processes. This change is linked to systemic symptoms of fatigue and cognitive impairment. To identify whether brain change occurs early in PBC. If the change develops early and is progressive, it may explain the difficulty in treating these symptoms. Early disease brain change was explored in 13 patients with newly diagnosed biopsy-proven precirrhotic PBC using magnetisation transfer, diffusion-weighted imaging and 1 H magnetic resonance spectroscopy. Results were compared to 17 healthy volunteers. Cerebral magnetisation transfer ratios were reduced in early PBC, compared to healthy volunteers, in the thalamus, putamen and head of caudate with no greater reduction in patients with greater symptom severity. Mean apparent diffusion coefficients were increased in the thalamus only. No 1 H magnetic resonance spectroscopy abnormalities were seen. Serum manganese levels were elevated in all PBC patients, but no relationship was seen with imaging or symptom parameters. There were no correlations between neuroimaging data, laboratory data, symptom severity scores or age. This is the first study to be performed in this precirrhotic patient population, and we have highlighted that neuroimaging changes are present at a much earlier stage than previously demonstrated. The neuroimaging abnormalities suggest that the brain changes seen in PBC occur early in the pathological process, even before significant liver damage has occurred. If such changes are linked to symptom pathogenesis, this could have important implications for the timing of second-line-therapy use. © 2016 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.
Computational Cognitive Neuroscience of Early Memory Development
ERIC Educational Resources Information Center
Munakata, Yuko
2004-01-01
Numerous brain areas work in concert to subserve memory, with distinct memory functions relying differentially on distinct brain areas. For example, semantic memory relies heavily on posterior cortical regions, episodic memory on hippocampal regions, and working memory on prefrontal cortical regions. This article reviews relevant findings from…
The Physiology of Moral Maturity.
ERIC Educational Resources Information Center
Hemming, James
1991-01-01
Discusses an evolutionary approach to human morality. Emphasizes the rapid development of brain weight, neural circuits, and synaptic systems during early childhood. Concludes that the human brain has resources for generating responsible, caring behavior but must be nurtured and educated. Urges that moral training in a proper social climate be…
Casas, Rafael; Muthusamy, Siva; Wakim, Paul G; Sinharay, Sanhita; Lentz, Margaret R; Reid, William C; Hammoud, Dima A
2018-01-01
HIV infection is known to be associated with brain volume loss, even in optimally treated patients. In this study, we assessed whether dynamic brain volume changes over time are predictive of neurobehavorial performance in the HIV-1 transgenic (Tg) rat, a model of treated HIV-positive patients. Cross-sectional brain MRI imaging was first performed comparing Tg and wild type (WT) rats at 3 and 19 months of age. Longitudinal MRI and neurobehavioral testing of another group of Tg and WT rats was then performed from 5 to 23 weeks of age. Whole brain and subregional image segmentation was used to assess the rate of brain growth over time. We used repeated-measures mixed models to assess differences in brain volumes and to establish how predictive the volume differences are of specific neurobehavioral deficits. Cross-sectional imaging showed smaller whole brain volumes in Tg compared to WT rats at 3 and at 19 months of age. Longitudinally, Tg brain volumes were smaller than age-matched WT rats at all time points, starting as early as 5 weeks of age. The Tg striatal growth rate delay between 5 and 9 weeks of age was greater than that of the whole brain. Striatal volume in combination with genotype was the most predictive of rota-rod scores and in combination with genotype and age was the most predictive of total exploratory activity scores in the Tg rats. The disproportionately delayed striatal growth compared to whole brain between 5 and 9 weeks of age and the role of striatal volume in predicting neurobehavioral deficits suggest an important role of the dopaminergic system in HIV associated neuropathology. This might explain problems with motor coordination and executive decisions in this animal model. Smaller brain and subregional volumes and neurobehavioral deficits were seen as early as 5 weeks of age, suggesting an early brain insult in the Tg rat. Neuroprotective therapy testing in this model should thus target this early stage of development, before brain damage becomes irreversible.
Studholme, Colin
2011-08-15
The development of tools to construct and investigate probabilistic maps of the adult human brain from magnetic resonance imaging (MRI) has led to advances in both basic neuroscience and clinical diagnosis. These tools are increasingly being applied to brain development in adolescence and childhood, and even to neonatal and premature neonatal imaging. Even earlier in development, parallel advances in clinical fetal MRI have led to its growing use as a tool in challenging medical conditions. This has motivated new engineering developments encompassing optimal fast MRI scans and techniques derived from computer vision, the combination of which allows full 3D imaging of the moving fetal brain in utero without sedation. These promise to provide a new and unprecedented window into early human brain growth. This article reviews the developments that have led us to this point, examines the current state of the art in the fields of fast fetal imaging and motion correction, and describes the tools to analyze dynamically changing fetal brain structure. New methods to deal with developmental tissue segmentation and the construction of spatiotemporal atlases are examined, together with techniques to map fetal brain growth patterns.
Gibson, Daniel A; Ma, Le
2011-08-01
Normal brain function relies not only on embryonic development when major neuronal pathways are established, but also on postnatal development when neural circuits are matured and refined. Misregulation at this stage may lead to neurological and psychiatric disorders such as autism and schizophrenia. Many genes have been studied in the prenatal brain and found crucial to many developmental processes. However, their function in the postnatal brain is largely unknown, partly because their deletion in mice often leads to lethality during neonatal development, and partly because their requirement in early development hampers the postnatal analysis. To overcome these obstacles, floxed alleles of these genes are currently being generated in mice. When combined with transgenic alleles that express Cre recombinase in specific cell types, conditional deletion can be achieved to study gene function in the postnatal brain. However, this method requires additional alleles and extra time (3-6 months) to generate the mice with appropriate genotypes, thereby limiting the expansion of the genetic analysis to a large scale in the mouse brain. Here we demonstrate a complementary approach that uses virally-expressed Cre to study these floxed alleles rapidly and systematically in postnatal brain development. By injecting recombinant adeno-associated viruses (rAAVs) encoding Cre into the neonatal brain, we are able to delete the gene of interest in different regions of the brain. By controlling the viral titer and coexpressing a fluorescent protein marker, we can simultaneously achieve mosaic gene inactivation and sparse neuronal labeling. This method bypasses the requirement of many genes in early development, and allows us to study their cell autonomous function in many critical processes in postnatal brain development, including axonal and dendritic growth, branching, and tiling, as well as synapse formation and refinement. This method has been used successfully in our own lab (unpublished results) and others, and can be extended to other viruses, such as lentivirus, as well as to the expression of shRNA or dominant active proteins. Furthermore, by combining this technique with electrophysiology as well as recently-developed optical imaging tools, this method provides a new strategy to study how genetic pathways influence neural circuit development and function in mice and rats.
Early Brain Vulnerability in Wolfram Syndrome
Hershey, Tamara; Lugar, Heather M.; Shimony, Joshua S.; Rutlin, Jerrel; Koller, Jonathan M.; Perantie, Dana C.; Paciorkowski, Alex R.; Eisenstein, Sarah A.; Permutt, M. Alan
2012-01-01
Wolfram Syndrome (WFS) is a rare autosomal recessive disease characterized by insulin-dependent diabetes mellitus, optic nerve atrophy, diabetes insipidus, deafness, and neurological dysfunction leading to death in mid-adulthood. WFS is caused by mutations in the WFS1 gene, which lead to endoplasmic reticulum (ER) stress-mediated cell death. Case studies have found widespread brain atrophy in late stage WFS. However, it is not known when in the disease course these brain abnormalities arise, and whether there is differential vulnerability across brain regions and tissue classes. To address this limitation, we quantified regional brain abnormalities across multiple imaging modalities in a cohort of young patients in relatively early stages of WFS. Children and young adults with WFS were evaluated with neurological, cognitive and structural magnetic resonance imaging measures. Compared to normative data, the WFS group had intact cognition, significant anxiety and depression, and gait abnormalities. Compared to healthy and type 1 diabetic control groups, the WFS group had smaller intracranial volume and preferentially affected gray matter volume and white matter microstructural integrity in the brainstem, cerebellum and optic radiations. Abnormalities were detected in even the youngest patients with mildest symptoms, and some measures did not follow the typical age-dependent developmental trajectory. These results establish that WFS is associated with smaller intracranial volume with specific abnormalities in the brainstem and cerebellum, even at the earliest stage of clinical symptoms. This pattern of abnormalities suggests that WFS has a pronounced impact on early brain development in addition to later neurodegenerative effects, representing a significant new insight into the WFS disease process. Longitudinal studies will be critical for confirming and expanding our understanding of the impact of ER stress dysregulation on brain development. PMID:22792385
Neuroimaging is a novel tool to understand the impact of environmental chemicals on neurodevelopment
Horton, Megan K.; Margolis, Amy E.; Tang, Cheuk; Wright, Robert
2014-01-01
Purpose of review The prevalence of childhood neurodevelopmental disorders (ND) has been increasing over the last several decades. Prenatal and early childhood exposure to environmental toxicants is increasingly recognized as contributing to the growing rate of NDs. Very little is known about the mechanistic processes by which environmental chemicals alter brain development. We review recent advances in brain imaging modalities and discuss their application in epidemiologic studies of prenatal and early childhood exposure to environmental toxicants. Recent findings Neuroimaging techniques (volumetric and functional magnetic resonance imaging (MRI), diffusor tensor imaging (DTI), magnetic resonance spectroscopy (MRS)) have opened unprecedented access to study the developing human brain. These techniques are non-invasive and free of ionization radiation making them suitable for research applications in children. Using these techniques, we now understand much about structural and functional patterns in the typically developing brain. This knowledge allows us to investigate how prenatal exposure to environmental toxicants may alter the typical developmental trajectory. Summary MRI is a powerful tool that allows in vivo visualization of brain structure and function. Used in epidemiologic studies of environmental exposure, it offers the promise to causally link exposure with behavioral and cognitive manifestations and ultimately to inform programs to reduce exposure and mitigate adverse effects of exposure. PMID:24535497
Scalable Joint Segmentation and Registration Framework for Infant Brain Images.
Dong, Pei; Wang, Li; Lin, Weili; Shen, Dinggang; Wu, Guorong
2017-03-15
The first year of life is the most dynamic and perhaps the most critical phase of postnatal brain development. The ability to accurately measure structure changes is critical in early brain development study, which highly relies on the performances of image segmentation and registration techniques. However, either infant image segmentation or registration, if deployed independently, encounters much more challenges than segmentation/registration of adult brains due to dynamic appearance change with rapid brain development. In fact, image segmentation and registration of infant images can assists each other to overcome the above challenges by using the growth trajectories (i.e., temporal correspondences) learned from a large set of training subjects with complete longitudinal data. Specifically, a one-year-old image with ground-truth tissue segmentation can be first set as the reference domain. Then, to register the infant image of a new subject at earlier age, we can estimate its tissue probability maps, i.e., with sparse patch-based multi-atlas label fusion technique, where only the training images at the respective age are considered as atlases since they have similar image appearance. Next, these probability maps can be fused as a good initialization to guide the level set segmentation. Thus, image registration between the new infant image and the reference image is free of difficulty of appearance changes, by establishing correspondences upon the reasonably segmented images. Importantly, the segmentation of new infant image can be further enhanced by propagating the much more reliable label fusion heuristics at the reference domain to the corresponding location of the new infant image via the learned growth trajectories, which brings image segmentation and registration to assist each other. It is worth noting that our joint segmentation and registration framework is also flexible to handle the registration of any two infant images even with significant age gap in the first year of life, by linking their joint segmentation and registration through the reference domain. Thus, our proposed joint segmentation and registration method is scalable to various registration tasks in early brain development studies. Promising segmentation and registration results have been achieved for infant brain MR images aged from 2-week-old to 1-year-old, indicating the applicability of our method in early brain development study.
Hazlett, Heather Cody; Poe, Michele D.; Lightbody, Amy A.; Styner, Martin; MacFall, James R.; Reiss, Allan L.; Piven, Joseph
2012-01-01
Objective To examine patterns of early brain growth in young children with fragile X syndrome (FXS) compared to a comparison group (controls) and a group with idiopathic autism. Method The study included 53 boys between 18–42 months of age with FXS, 68 boys with idiopathic autism (ASD), and a comparison group of 50 typically-developing and developmentally-delayed controls. We examined structural brain volumes using magnetic resonance imaging (MRI) across two timepoints between ages 2–3 and 4–5 years and examined total brain volumes and regional (lobar) tissue volumes. Additionally, we studied a selected group of subcortical structures implicated in the behavioral features of FXS (e.g., basal ganglia, hippocampus, amygdala). Results Children with FXS had greater global brain volumes compared to controls, but were not different than children with idiopathic autism, and the rate of brain growth between ages 2 and 5 paralleled that seen in controls. In contrast to the children with idiopathic autism who had generalized cortical lobe enlargement, the children with FXS showed a specific enlargement in temporal lobe white matter, cerebellar gray matter, and caudate nucleus, but significantly smaller amygdala. Conclusions This structural longitudinal MRI study of preschoolers with FXS observed generalized brain overgrowth in FXS compared to controls, evident at age 2 and maintained across ages 4–5. We also find different patterns of brain growth that distinguishes boys with FXS from children with idiopathic autism. PMID:22917205
ERIC Educational Resources Information Center
Betancourt, Laura M.; Avants, Brian; Farah, Martha J.; Brodsky, Nancy L.; Wu, Jue; Ashtari, Manzar; Hurt, Hallam
2016-01-01
There is increasing interest in both the cumulative and long-term impact of early life adversity on brain structure and function, especially as the brain is both highly vulnerable and highly adaptive during childhood. Relationships between SES and neural development have been shown in children older than age 2 years. Less is known regarding the…
ERIC Educational Resources Information Center
Ylinen, Sari; Bosseler, Alexis; Junttila, Katja; Huotilainen, Minna
2017-01-01
The ability to predict future events in the environment and learn from them is a fundamental component of adaptive behavior across species. Here we propose that inferring predictions facilitates speech processing and word learning in the early stages of language development. Twelve- and 24-month olds' electrophysiological brain responses to heard…
Epigenetics of the Developing Brain
ERIC Educational Resources Information Center
Champagne, Frances A.
2015-01-01
Advances in understanding of the dynamic molecular interplay between DNA and its surrounding proteins suggest that epigenetic mechanisms are a critical link between early life experiences (e.g., prenatal stress, parent-offspring interactions) and long-term changes in brain and behavior. Although much of this evidence comes from animal studies,…
Purposeful Play Leads to School Readiness
ERIC Educational Resources Information Center
Gilbert, Jaesook L.; Harte, Helene Arbouet; Patrick, Carol
2011-01-01
Initiatives such as the No Child Left Behind Act of 2001 (NCLB) reflect America's recent emphasis on literacy and educational accountability. Policymakers have a heightened interest in educating children earlier and fostering brain growth, in part due to the increased awareness of research on brain development and the importance of the early years…
Nair, Arun T; Ramachandran, Vadivelan; Joghee, Nanjan M; Antony, Shanish; Ramalingam, Gopalakrishnan
2018-01-01
Recent investigations suggest that gut microbiota affects the brain activity through the microbiota-gut-brain axis under both physiological and pathological disease conditions like Parkinson’s disease. Further dopamine synthesis in the brain is induced by dopamine producing enzymes that are controlled by gut microbiota via the microbiota-gut-brain axis. Also alpha synuclein deposition and the associated neurodegeneration in the enteric nervous system that increase intestinal permeability, oxidative stress, and local inflammation, accounts for constipation in Parkinson’s disease patients. The trigger that causes blood brain barrier leakage, immune cell activation and inflammation, and ultimately neuroinflammation in the central nervous system is believed to be due to the chronic low-grade inflammation in the gut. The non-motor symptoms that appear years before motor symptoms could be reliable early biomarkers, if they could be correlated with the established and reliable neuroimaging techniques or behavioral indices. The future directions should therefore, focus on the exploration of newer investigational techniques to identify these reliable early biomarkers and define the specific gut microbes that contribute to the development of Parkinson’s disease. This ultimately should pave the way to safer and novel therapeutic approaches that avoid the complications of the drugs delivered today to the brain of Parkinson’s disease patients. PMID:29291606
Margherio, Cara; Horner-Devine, M Claire; Mizumori, Sheri J Y; Yen, Joyce W
2016-01-01
Broadening the Representation of Academic Investigators in NeuroScience is a National Institutes of Health-funded, national program that addresses challenges to the persistence of diverse early-career neuroscientists. In doing so, BRAINS aims to advance diversity in neuroscience by increasing career advancement and retention of post-PhD, early-career neuroscientists from underrepresented groups (URGs). The comprehensive professional development program is structured to catalyze conversations specific to URGs in neuroscience and explicitly addresses factors known to impact persistence such as a weak sense of belonging to the scientific community, isolation and solo status, inequitable access to resources that impact career success, and marginalization from informal networks and mentoring relationships. While we do not yet have data on the long-term impact of the BRAINS program on participants' career trajectory and persistence, we introduce the BRAINS program theory and report early quantitative and qualitative data on shorter-term individual impacts within the realms of career-advancing behaviors and career experiences. These early results suggest promising, positive career productivity, increased self-efficacy, stronger sense of belonging, and new perspectives on navigating careers for BRAINS participants. We finish by discussing recommendations for future professional development programs and research designed to broaden participation in the biomedical and life sciences. © 2016 C. Margherio et al. CBE—Life Sciences Education © 2016 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).
Hoeijmakers, Lianne; Lucassen, Paul J.; Korosi, Aniko
2015-01-01
Early-life adversity increases the vulnerability to develop psychopathologies and cognitive decline later in life. This association is supported by clinical and preclinical studies. Remarkably, experiences of stress during this sensitive period, in the form of abuse or neglect but also early malnutrition or an early immune challenge elicit very similar long-term effects on brain structure and function. During early-life, both exogenous factors like nutrition and maternal care, as well as endogenous modulators, including stress hormones and mediator of immunological activity affect brain development. The interplay of these key elements and their underlying molecular mechanisms are not fully understood. We discuss here the hypothesis that exposure to early-life adversity (specifically stress, under/malnutrition and infection) leads to life-long alterations in hippocampal-related cognitive functions, at least partly via changes in hippocampal neurogenesis. We further discuss how these different key elements of the early-life environment interact and affect one another and suggest that it is a synergistic action of these elements that shapes cognition throughout life. Finally, we consider different intervention studies aiming to prevent these early-life adversity induced consequences. The emerging evidence for the intriguing interplay of stress, nutrition, and immune activity in the early-life programming calls for a more in depth understanding of the interaction of these elements and the underlying mechanisms. This knowledge will help to develop intervention strategies that will converge on a more complete set of changes induced by early-life adversity. PMID:25620909
ERIC Educational Resources Information Center
Knitzer, Jane; Lefkowitz, Jill
2006-01-01
Compelling evidence from neuroscience about how early relationships and experience influence the architecture of the brain, and in turn early school success, has led to increasing policy and practice attention to implementing child development and family support programs like Early Head Start for infants and toddlers. But, there is also a group of…
ERIC Educational Resources Information Center
Stark, Deborah Roderick
2016-01-01
With the achievement gap beginning to manifest in children as young as nine months, and 90 percent of brain development occurring during the first five years of life, chiefs are committed to expanding and upgrading early childhood programs and strengthening early elementary teaching and learning to provide equal educational opportunities for every…
Gut Microbiome and Infant Health: Brain-Gut-Microbiota Axis and Host Genetic Factors.
Cong, Xiaomei; Xu, Wanli; Romisher, Rachael; Poveda, Samantha; Forte, Shaina; Starkweather, Angela; Henderson, Wendy A
2016-09-01
The development of the neonatal gut microbiome is influenced by multiple factors, such as delivery mode, feeding, medication use, hospital environment, early life stress, and genetics. The dysbiosis of gut microbiota persists during infancy, especially in high-risk preterm infants who experience lengthy stays in the Neonatal intensive care unit (NICU). Infant microbiome evolutionary trajectory is essentially parallel with the host (infant) neurodevelopmental process and growth. The role of the gut microbiome, the brain-gut signaling system, and its interaction with the host genetics have been shown to be related to both short and long term infant health and bio-behavioral development. The investigation of potential dysbiosis patterns in early childhood is still lacking and few studies have addressed this host-microbiome co-developmental process. Further research spanning a variety of fields of study is needed to focus on the mechanisms of brain-gut-microbiota signaling system and the dynamic host-microbial interaction in the regulation of health, stress and development in human newborns.
Jernigan, Terry L.; Brown, Timothy T.; Bartsch, Hauke; Dale, Anders M.
2015-01-01
Based on the Huttenlocher lecture, this article describes the need for a more integrative scientific paradigm for addressing important questions raised by key observations made over 2 decades ago. Among these are the early descriptions by Huttenlocher of variability in synaptic density in cortex of postmortem brains of children of different ages and the almost simultaneous reports of cortical volume reductions on MR imaging in children and adolescents. In spite of much progress in developmental neurobiology, developmental cognitive neuroscience, and behavioral and imaging genetics, we still do not know how these early observations relate to each other. It is argued that large scale, collaborative research programs are needed to establish the associations between behavioral differences among children and imaging biomarkers, and to link the latter to cellular changes in the developing brain. Examples of progress and challenges remaining are illustrated with data from the Pediatric Imaging, Neurocognition, and Genetics Project (PING). PMID:26347228
The Lhx9 homeobox gene controls pineal gland development and prevents postnatal hydrocephalus.
Yamazaki, Fumiyoshi; Møller, Morten; Fu, Cong; Clokie, Samuel J; Zykovich, Artem; Coon, Steven L; Klein, David C; Rath, Martin F
2015-01-01
Lhx9 is a member of the LIM homeobox gene family. It is expressed during mammalian embryogenesis in the brain including the pineal gland. Deletion of Lhx9 results in sterility due to failure of gonadal development. The current study was initiated to investigate Lhx9 biology in the pineal gland. Lhx9 is highly expressed in the developing pineal gland of the rat with transcript abundance peaking early in development; transcript levels decrease postnatally to nearly undetectable levels in the adult, a temporal pattern that is generally similar to that reported for Lhx9 expression in other brain regions. Studies with C57BL/6J Lhx9(-/-) mutant mice revealed marked alterations in brain and pineal development. Specifically, the superficial pineal gland is hypoplastic, being reduced to a small cluster of pinealocytes surrounded by meningeal and vascular tissue. The deep pineal gland and the pineal stalk are also reduced in size. Although the brains of neonatal Lhx9(-/-) mutant mice appear normal, severe hydrocephalus develops in about 70% of the Lhx9(-/-) mice at 5-8 weeks of age; these observations are the first to document that deletion of Lhx9 results in hydrocephalus and as such indicate that Lhx9 contributes to the maintenance of normal brain structure. Whereas hydrocephalus is absent in neonatal Lhx9(-/-)mutant mice, the neonatal pineal gland in these animals is hypoplastic. Accordingly, it appears that Lhx9 is essential for early development of the mammalian pineal gland and that this effect is not secondary to hydrocephalus.
The Lhx9 homeobox gene controls pineal gland development and prevents postnatal hydrocephalus
Yamazaki, Fumiyoshi; Møller, Morten; Fu, Cong; Clokie, Samuel J.; Zykovich, Artem; Coon, Steven L.; Klein, David C.; Rath, Martin F.
2014-01-01
Lhx9 is a member of the LIM homeobox gene family. It is expressed during mammalian embryogenesis in the brain including the pineal gland. Deletion of Lhx9 results in sterility due to failure of gonadal development. The current study was initiated to investigate Lhx9 biology in the pineal gland. Lhx9 is highly expressed in the developing pineal gland of the rat with transcript abundance peaking early in development; transcript levels decrease postnatally to nearly undetectable levels in the adult, a temporal pattern that is generally similar to that reported for Lhx9 expression in other brain regions. Studies with C57BL/6J Lhx9−/− mutant mice revealed marked alterations in brain and pineal development. Specifically, the superficial pineal gland is hypoplastic, being reduced to a small cluster of pinealocytes surrounded by meningeal and vascular tissue. The deep pineal gland and the pineal stalk are also reduced in size. Although the brains of neonatal Lhx9−/− mutant mice appear normal, severe hydrocephalus develops in about 70 % of the Lhx9−/− mice at 5–8 weeks of age; these observations are the first to document that deletion of Lhx9 results in hydrocephalus and as such indicate that Lhx9 contributes to the maintenance of normal brain structure. Whereas hydrocephalus is absent in neonatal Lhx9−/−mutant mice, the neonatal pineal gland in these animals is hypoplastic. Accordingly, it appears that Lhx9 is essential for early development of the mammalian pineal gland and that this effect is not secondary to hydrocephalus. PMID:24647753
Vulnerability of children and the developing brain to neurotoxic hazards.
Weiss, B
2000-06-01
For much of the history of toxicology, the sensitivity of the developing organism to chemical perturbation attracted limited attention. Several tragic episodes and new insights finally taught us that the course of early brain development incurs unique risks. Although the process is exquisitely controlled, its lability renders it highly susceptible to damage from environmental chemicals. Such disturbances, as recognized by current testing protocols and legislation such as the Food Quality Protection Act, can result in outcomes ranging from death to malformations to functional impairment. The latter are the most difficult to determine. First, they require a variety of measures to assay their extent. Second, adult responses may prove an inadequate guide to the response of the developing brain, which is part of the reason for proposing additional safety factors for children. Third, neuropsychological tests are deployed in complex circumstances in which many factors, including economic status, combine to produce a particular effect such as lowered intelligence quotient score. Fourth, the magnitude of the effect, for most environmental exposure levels, may be relatively small but extremely significant for public health. Fifth, changes in brain function occur throughout life, and some consequences of early damage may not even emerge until advanced age. Such factors need to be addressed in estimating the influence of a particular agent or group of agents on brain development and its functional expression. It is especially important to consider ways of dealing with multiple risks and their combinations in addition to the prevailing practice of estimating risks in isolation.
Association of BDNF Val66Met Polymorphism and Brain BDNF Levels with Major Depression and Suicide.
Youssef, Mariam M; Underwood, Mark D; Huang, Yung-Yu; Hsiung, Shu-Chi; Liu, Yan; Simpson, Norman R; Bakalian, Mihran J; Rosoklija, Gorazd B; Dwork, Andrew J; Arango, Victoria; Mann, J John
2018-06-01
Brain-derived neurotrophic factor is implicated in the pathophysiology of major depressive disorder and suicide. Both are partly caused by early life adversity, which reduces brain-derived neurotrophic factor protein levels. This study examines the association of brain-derived neurotrophic factor Val66Met polymorphism and brain brain-derived neurotrophic factor levels with depression and suicide. We hypothesized that both major depressive disorder and early life adversity would be associated with the Met allele and lower brain brain-derived neurotrophic factor levels. Such an association would be consistent with low brain-derived neurotrophic factor mediating the effect of early life adversity on adulthood suicide and major depressive disorder. Brain-derived neurotrophic factor Val66Met polymorphism was genotyped in postmortem brains of 37 suicide decedents and 53 nonsuicides. Additionally, brain-derived neurotrophic factor protein levels were determined by Western blot in dorsolateral prefrontal cortex (Brodmann area 9), anterior cingulate cortex (Brodmann area 24), caudal brainstem, and rostral brainstem. The relationships between these measures and major depressive disorder, death by suicide, and reported early life adversity were examined. Subjects with the Met allele had an increased risk for depression. Depressed patients also have lower brain-derived neurotrophic factor levels in anterior cingulate cortex and caudal brainstem compared with nondepressed subjects. No effect of history of suicide death or early life adversity was observed with genotype, but lower brain-derived neurotrophic factor levels in the anterior cingulate cortex were found in subjects who had been exposed to early life adversity and/or died by suicide compared with nonsuicide decedents and no reported early life adversity. This study provides further evidence implicating low brain brain-derived neurotrophic factor and the brain-derived neurotrophic factor Met allele in major depression risk. Future studies should seek to determine how altered brain-derived neurotrophic factor expression contributes to depression and suicide.
Lim, Sanghee; Kwak, Minhye; Gray, Christy D.; Xu, Michael; Choi, Jun H.; Junn, Sue; Kim, Jieun; Xu, Jing; Schaefer, Michele; Johns, Roger A.; Song, Hongjun; Ming, Guo-Li; Mintz, C. David
2017-01-01
Clinical and preclinical studies indicate that early postnatal exposure to anesthetics can lead to lasting deficits in learning and other cognitive processes. The mechanism underlying this phenomenon has not been clarified and there is no treatment currently available. Recent evidence suggests that anesthetics might cause persistent deficits in cognitive function by disrupting key events in brain development. The hippocampus, a brain region that is critical for learning and memory, contains a large number of neurons that develop in the early postnatal period, which are thus vulnerable to perturbation by anesthetic exposure. Using an in vivo mouse model we demonstrate abnormal development of dendrite arbors and dendritic spines in newly generated dentate gyrus granule cell neurons of the hippocampus after a clinically relevant isoflurane anesthesia exposure conducted at an early postnatal age. Furthermore, we find that isoflurane causes a sustained increase in activity in the mechanistic target of rapamycin pathway, and that inhibition of this pathway with rapamycin not only reverses the observed changes in neuronal development, but also substantially improves performance on behavioral tasks of spatial learning and memory that are impaired by isoflurane exposure. We conclude that isoflurane disrupts the development of hippocampal neurons generated in the early postnatal period by activating a well-defined neurodevelopmental disease pathway and that this phenotype can be reversed by pharmacologic inhibition. PMID:28683067
Joven, Alberto; Morona, Ruth; Moreno, Nerea; González, Agustín
2013-07-01
The sequence of appearance of calretinin and calbindin-D28k immunoreactive (CRir and CBir, respectively) cells and fibers has been studied in the brain of the urodele amphibian Pleurodeles waltl. Embryonic, larval and juvenile stages were studied. The early expression and the dynamics of the distribution of CBir and CRir structures have been used as markers for developmental aspects of distinct neuronal populations, highlighting the accurate extent of many regions in the developing brain, not observed on the basis of cytoarchitecture alone. CR and, to a lesser extent, CB are expressed early in the central nervous system and show a progressively increasing expression from the embryonic stages throughout the larval life and, in general, the labeled structures in the developing brain retain their ability to express these proteins in the adult brain. The onset of CRir cells primarily served to follow the development of the olfactory bulbs, subpallium, thalamus, alar hypothalamus, mesencephalic tegmentum, and distinct cell populations in the rhombencephalic reticular formation. CBir cells highlighted the development of, among others, the pallidum, hypothalamus, dorsal habenula, midbrain tegmentum, cerebellum, and central gray of the rostral rhombencephalon. However, it was the relative and mostly segregated distribution of both proteins in distinct cell populations which evidenced the developing regionalization of the brain. The results have shown the usefulness in neuroanatomy of the analysis during development of the onset of CBir and CRir structures, but the comparison with previous data has shown extensive variability across vertebrate classes. Therefore, one should be cautious when comparing possible homologue structures across species only on the basis of the expression of these proteins, due to the variation of the content of calcium-binding proteins observed in well-established homologous regions in the brain of different vertebrates.
Professional fighters brain health study: rationale and methods.
Bernick, Charles; Banks, Sarah; Phillips, Michael; Lowe, Mark; Shin, Wanyong; Obuchowski, Nancy; Jones, Stephen; Modic, Michael
2013-07-15
Repetitive head trauma is a risk factor for Alzheimer's disease and is the primary cause of chronic traumatic encephalopathy. However, little is known about the natural history of, and risk factors for, chronic traumatic encephalopathy or about means of early detection and intervention. The Professional Fighters Brain Health Study is a longitudinal study of active professional fighters (boxers and mixed martial artists), retired professional fighters, and controls matched for age and level of education. The main objective of the Professional Fighters Brain Health Study is to determine the relationships between measures of head trauma exposure and other potential modifiers and changes in brain imaging and neurological and behavioral function over time. The study is designed to extend over 5 years, and we anticipate enrollment of more than 400 boxers and mixed martial artists. Participants will undergo annual evaluations that include 3-tesla magnetic resonance imaging scanning, computerized cognitive assessments, speech analysis, surveys of mood and impulsivity, and blood sampling for genotyping and exploratory biomarker studies. Statistical models will be developed and validated to predict early and progressive changes in brain structure and function. A composite fight exposure index, developed as a summary measure of cumulative traumatic exposure, shows promise as a predictor of brain volumes and cognitive function.
The development, past achievements, and future directions of brain PET
Jones, Terry; Rabiner, Eugenii A
2012-01-01
The early developments of brain positron emission tomography (PET), including the methodological advances that have driven progress, are outlined. The considerable past achievements of brain PET have been summarized in collaboration with contributing experts in specific clinical applications including cerebrovascular disease, movement disorders, dementia, epilepsy, schizophrenia, addiction, depression and anxiety, brain tumors, drug development, and the normal healthy brain. Despite a history of improving methodology and considerable achievements, brain PET research activity is not growing and appears to have diminished. Assessments of the reasons for decline are presented and strategies proposed for reinvigorating brain PET research. Central to this is widening the access to advanced PET procedures through the introduction of lower cost cyclotron and radiochemistry technologies. The support and expertize of the existing major PET centers, and the recruitment of new biologists, bio-mathematicians and chemists to the field would be important for such a revival. New future applications need to be identified, the scope of targets imaged broadened, and the developed expertize exploited in other areas of medical research. Such reinvigoration of the field would enable PET to continue making significant contributions to advance the understanding of the normal and diseased brain and support the development of advanced treatments. PMID:22434067
Copine1 regulates neural stem cell functions during brain development.
Kim, Tae Hwan; Sung, Soo-Eun; Cheal Yoo, Jae; Park, Jae-Yong; Yi, Gwan-Su; Heo, Jun Young; Lee, Jae-Ran; Kim, Nam-Soon; Lee, Da Yong
2018-01-01
Copine 1 (CPNE1) is a well-known phospholipid binding protein in plasma membrane of various cell types. In brain cells, CPNE1 is closely associated with AKT signaling pathway, which is important for neural stem cell (NSC) functions during brain development. Here, we investigated the role of CPNE1 in the regulation of brain NSC functions during brain development and determined its underlying mechanism. In this study, abundant expression of CPNE1 was observed in neural lineage cells including NSCs and immature neurons in human. With mouse brain tissues in various developmental stages, we found that CPNE1 expression was higher at early embryonic stages compared to postnatal and adult stages. To model developing brain in vitro, we used primary NSCs derived from mouse embryonic hippocampus. Our in vitro study shows decreased proliferation and multi-lineage differentiation potential in CPNE1 deficient NSCs. Finally, we found that the deficiency of CPNE1 downregulated mTOR signaling in embryonic NSCs. These data demonstrate that CPNE1 plays a key role in the regulation of NSC functions through the activation of AKT-mTOR signaling pathway during brain development. Copyright © 2017 Elsevier Inc. All rights reserved.
Cirulli, Francesca; Berry, Alessandra; Bonsignore, Luca Tommaso; Capone, Francesca; D'Andrea, Ivana; Aloe, Luigi; Branchi, Igor; Alleva, Enrico
2010-05-01
During the early post-natal phases the brain is experience-seeking and provided by a considerable plasticity which allows a fine tuning between the external environment and the developing organism. Since the early work of Seymour Levine, an impressive amount of research has clearly shown that stressful experiences exert powerful effects on the brain and body development. These effects can last throughout the entire life span influencing brain function and increasing the risk for depression and anxiety disorders. The mechanisms underlying the effects of early stress on the developing organism have been widely studied in rodents through experimental manipulations of the post-natal environment, such as handling, which have been shown to exert important effects on the emotional phenotype and the response to stress. In the present paper we review the relevant literature and present some original data indicating that, compared to handling, which imposes an external manipulation on the mother-infant relationship, social enrichment, in the form of communal rearing, in mice has very profound effects on animal's emotionality and the response to stress. These effects are also accompanied by important changes in central levels of brain-derived neurotrophic factor. The present data indicate that communal rearing has more pervasive effects than handling, strengthening previous data suggesting that it is a good animal model of reduced susceptibility to depression-like behavior. Overall, the availability of ever more sophisticated animal models represents a fundamental tool to translate basic research data into appropriate interventions for humans raised under traumatic or impoverished situations. (c) 2010 Elsevier Ltd. All rights reserved.
Iglesias, Marta; Almuedo-Castillo, Maria; Aboobaker, A Aziz; Saló, Emili
2011-10-01
Analysis of anteroposterior (AP) axis specification in regenerating planarian flatworms has shown that Wnt/β-catenin signaling is required for posterior specification and that the FGF-like receptor molecule nou-darake (ndk) may be involved in restricting brain regeneration to anterior regions. The relationship between re-establishment of AP identity and correct morphogenesis of the brain is, however, still poorly understood. Here we report the characterization of two axin paralogs in the planarian Schmidtea mediterranea. Although Axins are well known negative regulators of Wnt/β-catenin signaling, no role in AP specification has previously been reported for axin genes in planarians. We show that silencing of Smed-axin genes by RNA interference (RNAi) results in two-tailed planarians, a phenotype previously reported after silencing of Smed-APC-1, another β-catenin inhibitor. More strikingly, we show for the first time that while early brain formation at anterior wounds remains unaffected, subsequent development of the brain is blocked in the two-tailed planarians generated after silencing of Smed-axin genes and Smed-APC-1. These findings suggest that the mechanisms underlying early brain formation can be uncoupled from the specification of AP identity by the Wnt/β-catenin pathway. Finally, the posterior expansion of the brain observed following Smed-ndk RNAi is enhanced by silencing Smed-APC-1, revealing an indirect relationship between the FGFR/Ndk and Wnt/β-catenin signaling systems in establishing the posterior limits of brain differentiation. Copyright © 2011 Elsevier Inc. All rights reserved.
A starring role for microglia in brain sex differences.
Lenz, Kathryn M; McCarthy, Margaret M
2015-06-01
Microglia, the resident innate immune cells in the brain, have long been understood to be crucial to maintenance in the nervous system, by clearing debris, monitoring for infiltration of infectious agents, and mediating the brain's inflammatory and repair response to traumatic injury, stroke, or neurodegeneration. A wave of new research has shown that microglia are also active players in many basic processes in the healthy brain, including cell proliferation, synaptic connectivity, and physiology. Microglia, both in their capacity as phagocytic cells and via secretion of many neuroactive molecules, including cytokines and growth factors, play a central role in early brain development, including sexual differentiation of the brain. In this review, we present the vast roles microglia play in normal brain development and how perturbations in the normal neuroimmune environment during development may contribute to the etiology of brain-based disorders. There are notable differences between microglia and neuroimmune signaling in the male and female brain throughout the life span, and these differences may contribute to the vast differences in the incidence of neuropsychiatric and neurological disorders between males and females. © The Author(s) 2014.
Intervention strategies for cesarean section–induced alterations in the microbiota-gut-brain axis
Moya-Pérez, Angela; Luczynski, Pauline; Renes, Ingrid B.; Wang, Shugui; Borre, Yuliya; Anthony Ryan, C.; Knol, Jan; Stanton, Catherine; Dinan, Timothy G.
2017-01-01
Microbial colonization of the gastrointestinal tract is an essential process that modulates host physiology and immunity. Recently, researchers have begun to understand how and when these microorganisms colonize the gut and the early-life factors that impact their natural ecological establishment. The vertical transmission of maternal microbes to the offspring is a critical factor for host immune and metabolic development. Increasing evidence also points to a role in the wiring of the gut-brain axis. This process may be altered by various factors such as mode of delivery, gestational age at birth, the use of antibiotics in early life, infant feeding, and hygiene practices. In fact, these early exposures that impact the intestinal microbiota have been associated with the development of diseases such as obesity, type 1 diabetes, asthma, allergies, and even neurodevelopmental disorders. The present review summarizes the impact of cesarean birth on the gut microbiome and the health status of the developing infant and discusses possible preventative and restorative strategies to compensate for early-life microbial perturbations. PMID:28379454
Brain Imaging and Human Nutrition: Which Measures to Use in Intervention Studies?12
Sizonenko, Stéphane V.; Babiloni, Claudio; Sijben, John W.; Walhovd, Kristine B.
2013-01-01
Throughout the life span, the brain is a metabolically highly active organ that uses a large proportion of total nutrient and energy intake. Furthermore, the development and repair of neural tissue depend on the proper intake of essential structural nutrients, minerals, and vitamins. Therefore, what we eat, or refrain from eating, may have an important impact on our cognitive ability and mental performance. Two of the key areas in which diet is thought to play an important role are in optimizing neurodevelopment in children and in preventing neurodegeneration and cognitive decline during aging. From early development to aging, brain imaging can detect structural, functional, and metabolic changes in humans and modifications due to altered nutrition or to additional nutritional supplementation. Inclusion of imaging measures in clinical studies can increase understanding with regard to the modification of brain structure, metabolism, and functional endpoints and may provide early sensitive measures of long-term effects. In this symposium, the utility of existing brain imaging technologies to assess the effects of nutritional intervention in humans is described. Examples of current research showing the utility of these markers are reviewed. PMID:24038255
Effects of Anesthetics on Brain Circuit Formation
Wagner, Meredith; Ryu, Yun Kyoung; Smith, Sarah C.; Mintz, C. David
2014-01-01
The results of several retrospective clinical studies suggest that exposure to anesthetic agents early in life is correlated with subsequent learning and behavioral disorders. While ongoing prospective clinical trials may help to clarify this association, they remain confounded by numerous factors. Thus, some of the most compelling data supporting the hypothesis that a relatively short anesthetic exposure can lead to a long-lasting change in brain function are derived from animal models. The mechanism by which such changes could occur remains incompletely understood. Early studies identified anesthetic-induced neuronal apoptosis as a possible mechanism of injury, and more recent work suggests that anesthetics may interfere with several critical processes in brain development. The function of the mature brain requires the presence of circuits, established during development, that perform the computations underlying learning and cognition. In this review we examine the mechanisms by which anesthetics could disrupt brain circuit formation, including effects on neuronal survival and neurogenesis, neurite growth and guidance, formation of synapses, and function of supporting cells. There is evidence that anesthetics can disrupt aspects of all of these processes, and further research is required to elucidate which are most relevant to pediatric anesthetic neurotoxicity. PMID:25144504
Sakai, Tomoko; Matsui, Mie; Mikami, Akichika; Malkova, Ludise; Hamada, Yuzuru; Tomonaga, Masaki; Suzuki, Juri; Tanaka, Masayuki; Miyabe-Nishiwaki, Takako; Makishima, Haruyuki; Nakatsukasa, Masato; Matsuzawa, Tetsuro
2013-02-22
Developmental prolongation is thought to contribute to the remarkable brain enlargement observed in modern humans (Homo sapiens). However, the developmental trajectories of cerebral tissues have not been explored in chimpanzees (Pan troglodytes), even though they are our closest living relatives. To address this lack of information, the development of cerebral tissues was tracked in growing chimpanzees during infancy and the juvenile stage, using three-dimensional magnetic resonance imaging and compared with that of humans and rhesus macaques (Macaca mulatta). Overall, cerebral development in chimpanzees demonstrated less maturity and a more protracted course during prepuberty, as observed in humans but not in macaques. However, the rapid increase in cerebral total volume and proportional dynamic change in the cerebral tissue in humans during early infancy, when white matter volume increases dramatically, did not occur in chimpanzees. A dynamic reorganization of cerebral tissues of the brain during early infancy, driven mainly by enhancement of neuronal connectivity, is likely to have emerged in the human lineage after the split between humans and chimpanzees and to have promoted the increase in brain volume in humans. Our findings may lead to powerful insights into the ontogenetic mechanism underlying human brain enlargement.
Sakai, Tomoko; Matsui, Mie; Mikami, Akichika; Malkova, Ludise; Hamada, Yuzuru; Tomonaga, Masaki; Suzuki, Juri; Tanaka, Masayuki; Miyabe-Nishiwaki, Takako; Makishima, Haruyuki; Nakatsukasa, Masato; Matsuzawa, Tetsuro
2013-01-01
Developmental prolongation is thought to contribute to the remarkable brain enlargement observed in modern humans (Homo sapiens). However, the developmental trajectories of cerebral tissues have not been explored in chimpanzees (Pan troglodytes), even though they are our closest living relatives. To address this lack of information, the development of cerebral tissues was tracked in growing chimpanzees during infancy and the juvenile stage, using three-dimensional magnetic resonance imaging and compared with that of humans and rhesus macaques (Macaca mulatta). Overall, cerebral development in chimpanzees demonstrated less maturity and a more protracted course during prepuberty, as observed in humans but not in macaques. However, the rapid increase in cerebral total volume and proportional dynamic change in the cerebral tissue in humans during early infancy, when white matter volume increases dramatically, did not occur in chimpanzees. A dynamic reorganization of cerebral tissues of the brain during early infancy, driven mainly by enhancement of neuronal connectivity, is likely to have emerged in the human lineage after the split between humans and chimpanzees and to have promoted the increase in brain volume in humans. Our findings may lead to powerful insights into the ontogenetic mechanism underlying human brain enlargement. PMID:23256194
Whittle, Sarah; Vijayakumar, Nandita; Simmons, Julian G; Dennison, Meg; Schwartz, Orli; Pantelis, Christos; Sheeber, Lisa; Byrne, Michelle L; Allen, Nicholas B
2017-08-01
The negative effects of socioeconomic disadvantage on lifelong functioning are pronounced, with some evidence suggesting that these effects are mediated by changes in brain development. To our knowledge, no research has investigated whether parenting might buffer these negative effects. To establish whether positive parenting behaviors moderate the effects of socioeconomic disadvantage on brain development and adaptive functioning in adolescents. In this longitudinal study of adolescents from schools in Melbourne, Australia, data were collected at 3 assessments between 2004 and 2012. Data were analyzed between August 2016 and April 2017. Both family (parental income-to-needs, occupation, and education level) and neighborhood measures of socioeconomic disadvantage were assessed. Positive maternal parenting behaviors were observed during interactions in early adolescence. Structural magnetic resonance imaging scans at 3 times (early, middle, and late adolescence) from ages 11 to 20 years. Global and academic functioning was assessed during late adolescence. We used linear mixed models to examine the effect of family and neighborhood socioeconomic disadvantage as well as the moderating effect of positive parenting on adolescent brain development. We used mediation models to examine whether brain developmental trajectories predicted functional outcomes during late adolescence. Of the included 166 adolescents, 86 (51.8%) were male. We found that neighborhood, but not family, socioeconomic disadvantage was associated with altered brain development from early (mean [SD] age, 12.79 [0.425] years) to late (mean [SD] age, 19.08 [0.460] years) adolescence, predominantly in the temporal lobes (temporal cortex: random field theory corrected; left amygdala: B, -0.237; P < .001; right amygdala: B, -0.209; P = .008). Additionally, positive parenting moderated the effects of neighborhood disadvantage on the development of dorsal frontal and lateral orbitofrontal cortices as well as the effects of family disadvantage on the development of the amygdala (occupation: B, 0.382; P = .004; income-to-needs: B, 27.741; P = .004), with some male-specific findings. The pattern of dorsal frontal cortical development in males from disadvantaged neighborhoods exposed to low maternal positivity predicted increased rates of school noncompletion (indirect effect, -0.018; SE, 0.01; 95% CI, -0.053 to -0.001). Our findings highlight the importance of neighborhood disadvantage in influencing brain developmental trajectories. Further, to our knowledge, we present the first evidence that positive maternal parenting might ameliorate the negative effects of socioeconomic disadvantage on frontal lobe development (with implications for functioning) during adolescence. Results have relevance for designing interventions for children from socioeconomically disadvantaged backgrounds.
Nikolakopoulou, Angeliki Maria; Zhao, Zhen; Montagne, Axel; Zlokovic, Berislav V
2017-01-01
Pericytes regulate key neurovascular functions of the brain. Studies in pericyte-deficient transgenic mice with aberrant signaling between endothelial-derived platelet-derived growth factor BB (PDGF-BB) and platelet-derived growth factor receptor β (PDGFRβ) in pericytes have contributed to better understanding of the role of pericytes in the brain. Here, we studied PdgfrβF7/F7 mice, which carry seven point mutations that disrupt PDGFRβ signaling causing loss of pericytes and vascular smooth muscle cells (VSMCs) in the developing brain. We asked whether these mice have a stable or progressive vascular phenotype after birth, and whether both pericyte and VSMCs populations are affected in the adult brain. We found an early and progressive region-dependent loss of brain pericytes, microvascular reductions and blood-brain barrier (BBB) breakdown, which were more pronounced in the cortex, hippocampus and striatum than in the thalamus, whereas VSMCs population remained unaffected at the time when pericyte loss was already established. For example, compared to age-matched controls, PdgfrβF7/F7 mice between 4-6 and 36-48 weeks of age developed a region-dependent loss in pericyte coverage (22-46, 24-44 and 4-31%) and cell numbers (36-49, 34-64 and 11-36%), reduction in capillary length (20-39, 13-46 and 1-30%), and an increase in extravascular fibrinogen-derived deposits (3.4-5.2, 2.8-4.1 and 0-3.6-fold) demonstrating BBB breakdown in the cortex, hippocampus and thalamus, respectively. Capillary reductions and BBB breakdown correlated with loss of pericyte coverage. Our data suggest that PdgfrβF7/F7 mice develop an aggressive and rapid vascular phenotype without appreciable early involvement of VSMCs, therefore providing a valuable model to study regional effects of pericyte loss on brain vascular and neuronal functions. This model could be a useful tool for future studies directed at understanding the role of pericytes in the pathogenesis of neurological disorders associated with pericyte loss such as vascular dementia, Alzheimer's disease, amyotrophic lateral sclerosis, stroke and human immunodeficiency virus-associated neurocognitive disorder.
Evans, Tanya M; Kochalka, John; Ngoon, Tricia J; Wu, Sarah S; Qin, Shaozheng; Battista, Christian; Menon, Vinod
2015-08-19
Early numerical proficiency lays the foundation for acquiring quantitative skills essential in today's technological society. Identification of cognitive and brain markers associated with long-term growth of children's basic numerical computation abilities is therefore of utmost importance. Previous attempts to relate brain structure and function to numerical competency have focused on behavioral measures from a single time point. Thus, little is known about the brain predictors of individual differences in growth trajectories of numerical abilities. Using a longitudinal design, with multimodal imaging and machine-learning algorithms, we investigated whether brain structure and intrinsic connectivity in early childhood are predictive of 6 year outcomes in numerical abilities spanning childhood and adolescence. Gray matter volume at age 8 in distributed brain regions, including the ventrotemporal occipital cortex (VTOC), the posterior parietal cortex, and the prefrontal cortex, predicted longitudinal gains in numerical, but not reading, abilities. Remarkably, intrinsic connectivity analysis revealed that the strength of functional coupling among these regions also predicted gains in numerical abilities, providing novel evidence for a network of brain regions that works in concert to promote numerical skill acquisition. VTOC connectivity with posterior parietal, anterior temporal, and dorsolateral prefrontal cortices emerged as the most extensive network predicting individual gains in numerical abilities. Crucially, behavioral measures of mathematics, IQ, working memory, and reading did not predict children's gains in numerical abilities. Our study identifies, for the first time, functional circuits in the human brain that scaffold the development of numerical skills, and highlights potential biomarkers for identifying children at risk for learning difficulties. Children show substantial individual differences in math abilities and ease of math learning. Early numerical abilities provide the foundation for future academic and professional success in an increasingly technological society. Understanding the early identification of poor math skills has therefore taken on great significance. This work provides important new insights into brain structure and connectivity measures that can predict longitudinal growth of children's math skills over a 6 year period, and may eventually aid in the early identification of children who might benefit from targeted interventions. Copyright © 2015 the authors 0270-6474/15/3511743-08$15.00/0.
Cannabis and alcohol use, and the developing brain.
Meruelo, A D; Castro, N; Cota, C I; Tapert, S F
2017-05-15
Sex hormones and white (and grey) matter in the limbic system, cortex and other brain regions undergo changes during adolescence. Some of these changes include ongoing white matter myelination and sexually dimorphic features in grey and white matter. Adolescence is also a period of vulnerability when many are first exposed to alcohol and cannabis, which appear to influence the developing brain. Neuropsychological studies have provided considerable understanding of the effects of alcohol and cannabis on the brain. Advances in neuroimaging have allowed examination of neuroanatomic changes, metabolic and neurotransmitter activity, and neuronal activation during adolescent brain development and substance use. In this review, we examine major differences in brain development between users and non-users, and recent findings on the influence of cannabis and alcohol on the adolescent brain. We also discuss associations that appear to resolve following short-term abstinence, and attentional deficits that appear to persist. These findings can be useful in guiding earlier educational interventions for adolescents, and clarifying the neural sequelae of early alcohol and cannabis use to the general public. Copyright © 2017 Elsevier B.V. All rights reserved.
Cannabis and Alcohol Use, and the Developing Brain
Meruelo, AD; Castro, N; Cota, CI; Tapert, SF
2017-01-01
Sex hormones and white (and grey) matter in the limbic system, cortex and other brain regions undergo changes during adolescence. Some of these changes include ongoing white matter myelination and sexually dimorphic features in grey and white matter. Adolescence is also a period of vulnerability when many are first exposed to alcohol and cannabis, which appear to influence the developing brain. Neuropsychological studies have provided considerable understanding of the effects of alcohol and cannabis on the brain. Advances in neuroimaging have allowed examination of neuroanatomic changes, metabolic and neurotransmitter activity, and neuronal activation during adolescent brain development and substance use. In this review, we examine major differences in brain development between users and non-users, and recent findings on the influence of cannabis and alcohol on the adolescent brain. We also discuss associations that appear to resolve following short-term abstinence, and attentional deficits that appear to persist. These findings can be useful in guiding earlier educational interventions for adolescents, and clarifying the neural sequelae of early alcohol and cannabis use to the general public. PMID:28223098
Raineki, Charlis; Bodnar, Tamara S; Holman, Parker J; Baglot, Samantha L; Lan, Ni; Weinberg, Joanne
2017-11-01
The contribution of the early postnatal environment to the pervasive effects of prenatal alcohol exposure (PAE) is poorly understood. Moreover, PAE often carries increased risk of exposure to adversity/stress during early life. Dysregulation of immune function may play a role in how pre- and/or postnatal adversity/stress alters brain development. Here, we combine two animal models to examine whether PAE differentially increases vulnerability to immune dysregulation in response to early-life adversity. PAE and control litters were exposed to either limited bedding (postnatal day [PN] 8-12) to model early-life adversity or normal bedding, and maternal behavior and pup vocalizations were recorded. Peripheral (serum) and central (amygdala) immune (cytokines and C-reactive protein - CRP) responses of PAE animals to early-life adversity were evaluated at PN12. Insufficient bedding increased negative maternal behavior in both groups. Early-life adversity increased vocalization in all animals; however, PAE pups vocalized less than controls. Early-life adversity reduced serum TNF-α, KC/GRO, and IL-10 levels in control but not PAE animals. PAE increased serum CRP, and levels were even higher in pups exposed to adversity. Finally, PAE reduced KC/GRO and increased IL-10 levels in the amygdala. Our results indicate that PAE alters immune system development and both behavioral and immune responses to early-life adversity, which could have subsequent consequences for brain development and later life health. Copyright © 2017 Elsevier Inc. All rights reserved.
Castillo-Gómez, Esther; Pérez-Rando, Marta; Bellés, María; Gilabert-Juan, Javier; Llorens, José Vicente; Carceller, Héctor; Bueno-Fernández, Clara; García-Mompó, Clara; Ripoll-Martínez, Beatriz; Curto, Yasmina; Sebastiá-Ortega, Noelia; Moltó, María Dolores; Sanjuan, Julio; Nacher, Juan
2017-01-01
The exposure to aversive experiences during early life influences brain development and leads to altered behavior. Moreover, the combination of these experiences with subtle alterations in neurodevelopment may contribute to the emergence of psychiatric disorders, such as schizophrenia. Recent hypotheses suggest that imbalances between excitatory and inhibitory (E/I) neurotransmission, especially in the prefrontal cortex and the amygdala, may underlie their etiopathology. In order to understand better the neurobiological bases of these alterations, we studied the impact of altered neurodevelopment and chronic early-life stress on these two brain regions. Transgenic mice displaying fluorescent excitatory and inhibitory neurons, received a single injection of MK801 (NMDAR antagonist) or vehicle solution at postnatal day 7 and/or were socially isolated from the age of weaning until adulthood (3 months old). We found that anxiety-related behavior, brain volume, neuronal structure, and the expression of molecules related to plasticity and E/I neurotransmission in adult mice were importantly affected by early-life stress. Interestingly, many of these effects were potentiated when the stress paradigm was applied to mice perinatally injected with MK801 ("double-hit" model). These results clearly show the impact of early-life stress on the adult brain, especially on the structure and plasticity of inhibitory networks, and highlight the double-hit model as a valuable tool to study the contribution of early-life stress in the emergence of neurodevelopmental psychiatric disorders, such as schizophrenia.
ERIC Educational Resources Information Center
Turati, Chiara; Natale, Elena; Bolognini, Nadia; Senna, Irene; Picozzi, Marta; Longhi, Elena; Cassia, Viola Macchi
2013-01-01
In primates and adult humans direct understanding of others' action is provided by mirror mechanisms matching action observation and action execution (e.g. Casile, Caggiano & Ferrari, 2011). Despite the growing body of evidence detailing the existence of these mechanisms in the adult human brain, their origins and early development are…
ERIC Educational Resources Information Center
Friedman, Dorian
2006-01-01
By bringing together neurologists, developmental psychologists, pediatricians, and economists, the National Scientific Council on the Developing Child offers a unique knowledge base from which early childhood policy and practice can be informed. By communicating how and why early experiences have a lasting impact on brain architecture--and what…
Perinatal programming of emotional brain circuits: an integrative view from systems to molecules
Bock, Jörg; Rether, Kathy; Gröger, Nicole; Xie, Lan; Braun, Katharina
2014-01-01
Environmental influences such as perinatal stress have been shown to program the developing organism to adapt brain and behavioral functions to cope with daily life challenges. Evidence is now accumulating that the specific and individual effects of early life adversity on the functional development of brain and behavior emerge as a function of the type, intensity, timing and the duration of the adverse environment, and that early life stress (ELS) is a major risk factor for developing behavioral dysfunctions and mental disorders. Results from clinical as well as experimental studies in animal models support the hypothesis that ELS can induce functional “scars” in prefrontal and limbic brain areas, regions that are essential for emotional control, learning and memory functions. On the other hand, the concept of “stress inoculation” is emerging from more recent research, which revealed positive functional adaptations in response to ELS resulting in resilience against stress and other adversities later in life. Moreover, recent studies indicate that early life experiences and the resulting behavioral consequences can be transmitted to the next generation, leading to a transgenerational cycle of adverse or positive adaptations of brain function and behavior. In this review we propose a unifying view of stress vulnerability and resilience by connecting genetic predisposition and programming sensitivity to the context of experience-expectancy and transgenerational epigenetic traits. The adaptive maturation of stress responsive neural and endocrine systems requires environmental challenges to optimize their functions. Repeated environmental challenges can be viewed within the framework of the match/mismatch hypothesis, the outcome, psychopathology or resilience, depends on the respective predisposition and on the context later in life. PMID:24550772
Kesby, James P; Cui, Xiaoying; Burne, Thomas H J; Eyles, Darryl W
2013-01-01
Schizophrenia is a heterogeneous group of disorders with unknown etiology. Although abnormalities in multiple neurotransmitter systems have been linked to schizophrenia, alterations in dopamine (DA) neurotransmission remain central to the treatment of this disorder. Given that schizophrenia is considered a neurodevelopmental disorder we have hypothesized that abnormal DA signaling in the adult patient may result from altered DA signaling during fetal brain development. Environmental and genetic risk factors can be modeled in rodents to allow for the investigation of early neurodevelopmental pathogenesis that may lead to clues into the etiology of schizophrenia. To address this we created an animal model of one such risk factor, developmental vitamin D (DVD) deficiency. DVD-deficient adult rats display an altered behavioral profile in response to DA releasing and blocking agents that are reminiscent of that seen in schizophrenia patients. Furthermore, developmental studies revealed that DVD deficiency also altered cell proliferation, apoptosis, and neurotransmission across the embryonic brain. In particular, DVD deficiency reduces the expression of crucial dopaminergic specification factors and alters DA metabolism in the developing brain. We speculate such alterations in fetal brain development may change the trajectory of DA neuron ontogeny to induce the behavioral abnormalities observed in adult offspring. The widespread evidence that both dopaminergic and structural changes are present in people who develop schizophrenia prior to onset also suggest that early alterations in development are central to the disease. Taken together, early alterations in DA ontogeny may represent a core feature in the pathology of schizophrenia. Such a mechanism could bring together evidence from multiple risk factors and genetic vulnerabilities to form a convergent pathway in disease pathophysiology.
Bick, Johanna; Zhu, Tong; Stamoulis, Catherine; Fox, Nathan A; Zeanah, Charles; Nelson, Charles A
2015-03-01
Severe neglect in early life is associated with compromises in brain development and associated behavioral functioning. Although early intervention has been shown to support more normative trajectories of brain development, specific improvements in the white matter pathways that underlie emotional and cognitive development are unknown. To examine associations among neglect in early life, early intervention, and the microstructural integrity of white matter pathways in middle childhood. The Bucharest Early Intervention Project is a randomized clinical trial of high-quality foster care as an intervention for institutionally reared children in Bucharest, Romania, from 2000 through the present. During infancy, children were randomly selected to remain in an institution or to be placed in foster care. Those who remained in institutions experienced neglect, including social, emotional, linguistic, and cognitive impoverishment. Developmental trajectories of these children were compared with a group of sociodemographically matched children reared in biological families at baseline and several points throughout development. At approximately 8 years of age, 69 of the original 136 children underwent structural magnetic resonance imaging scans. Four estimates of white matter integrity (fractional anisotropy [FA] and mean [MD], radial [RD], and axial [AD] diffusivity) for 48 white matter tracts throughout the brain were obtained through diffusion tensor imaging. Significant associations emerged between neglect in early life and microstructural integrity of the body of the corpus callosum (FA, β = 0.01 [P = .01]; RD, β = -0.02 [P = .005]; MD, β = -0.01 [P = .02]) and tracts involved in limbic circuitry (fornix crus [AD, β = 0.02 (P = .046)] and cingulum [RD, β = -0.01 (P = .02); MD, β = -0.01 (P = .049)]), frontostriatal circuitry (anterior [AD, β = -0.01 (P = .02)] and superior [AD, β = -0.02 (P = .02); MD, β = -0.01 (P = .03)] corona radiata and external capsule [right FA, β = 0.01 (P = .03); left FA, β = 0.01 (P = .03); RD, β = -0.01 (P = .01); MD, β = -0.01 (P = .03)]), and sensory processing (medial lemniscus [AD, β = -0.02 (P = .045); MD, β = -0.01 (P = .04)] and retrolenticular internal capsule [FA, β = -0.01 (P = .002); RD, β = 0.01 (P = .003); MD, β = 0.01 (P = .04)]). Follow-up analyses revealed that early intervention promoted more normative white matter development among previously neglected children who entered foster care. Results suggest that removal from conditions of neglect in early life and entry into a high-quality family environment can support more normative trajectories of white matter growth. Our findings have implications for public health and policy efforts designed to promote normative brain development among vulnerable children. clinicaltrials.gov Identifier: NCT00747396.
ERIC Educational Resources Information Center
Hayes, Cheryl D.; Flynn, Margaret J.; Stebbins, Helene
2004-01-01
Ensuring that children enter school ready to learn is now a well-established national goal. Dramatic changes over the past three decades in U.S. families and the economy, as well as emerging research on the importance of early brain development, have increased the demand for public investments in early childhood supports and services, especially…
Early brain connectivity alterations and cognitive impairment in a rat model of Alzheimer's disease.
Muñoz-Moreno, Emma; Tudela, Raúl; López-Gil, Xavier; Soria, Guadalupe
2018-02-07
Animal models of Alzheimer's disease (AD) are essential to understanding the disease progression and to development of early biomarkers. Because AD has been described as a disconnection syndrome, magnetic resonance imaging (MRI)-based connectomics provides a highly translational approach to characterizing the disruption in connectivity associated with the disease. In this study, a transgenic rat model of AD (TgF344-AD) was analyzed to describe both cognitive performance and brain connectivity at an early stage (5 months of age) before a significant concentration of β-amyloid plaques is present. Cognitive abilities were assessed by a delayed nonmatch-to-sample (DNMS) task preceded by a training phase where the animals learned the task. The number of training sessions required to achieve a learning criterion was recorded and evaluated. After DNMS, MRI acquisition was performed, including diffusion-weighted MRI and resting-state functional MRI, which were processed to obtain the structural and functional connectomes, respectively. Global and regional graph metrics were computed to evaluate network organization in both transgenic and control rats. The results pointed to a delay in learning the working memory-related task in the AD rats, which also completed a lower number of trials in the DNMS task. Regarding connectivity properties, less efficient organization of the structural brain networks of the transgenic rats with respect to controls was observed. Specific regional differences in connectivity were identified in both structural and functional networks. In addition, a strong correlation was observed between cognitive performance and brain networks, including whole-brain structural connectivity as well as functional and structural network metrics of regions related to memory and reward processes. In this study, connectivity and neurocognitive impairments were identified in TgF344-AD rats at a very early stage of the disease when most of the pathological hallmarks have not yet been detected. Structural and functional network metrics of regions related to reward, memory, and sensory performance were strongly correlated with the cognitive outcome. The use of animal models is essential for the early identification of these alterations and can contribute to the development of early biomarkers of the disease based on MRI connectomics.
Liu, Jianghong; Zhao, Sophie R.; Reyes, Teresa
2015-01-01
In recent years, a role for epigenetic modifications in the pathophysiology of disease has received significant attention. Many studies are now beginning to explore the gene–environment interactions, which may mediate early-life exposure to risk factors, such as nutritional deficiencies and later development of behavioral problems in children and adults. In this paper, we review the current literature on the role of epigenetics in the development of psychopathology, with a specific focus on the potential for epigenetic modifications to link nutrition and brain development. We propose a conceptual framework whereby epigenetic modifications (e.g., DNA methylation) mediate the link between micro- and macro-nutrient deficiency early in life and brain dysfunction (e.g., structural aberration, neurotransmitter perturbation), which has been linked to development of behavior problems later on in life. PMID:26251900
ERIC Educational Resources Information Center
Jager, Gerry; Block, Robert I.; Luijten, Maartje; Ramsey, Nick F.
2010-01-01
Objective: Early-onset cannabis use has been associated with later use/abuse, mental health problems (psychosis, depression), and abnormal development of cognition and brain function. During adolescence, ongoing neurodevelopmental maturation and experience shape the neural circuitry underlying complex cognitive functions such as memory and…
Undernutrition and the Developing Brain: The Relevance of Animal Models to the Human Problem
ERIC Educational Resources Information Center
Dobbing, John
1972-01-01
Discusses evidence for a permanent, measurable effect of early restriction on the physical growth of the brain, arguing that undernutrition has been considered for too long in adult terms as a series of deficiency diseases whose main consequences can be reversed on restoration of the deficient component. (Author/JM)
Connective Intelligence for Childhood Mathematics Education
ERIC Educational Resources Information Center
Novo, María-Luisa; Alsina, Ángel; Marbán, José-María; Berciano, Ainhoa
2017-01-01
The construction of a connective brain begins at the earliest ages of human development. However, knowledge about individual and collective brains provided so far by research has been rarely incorporated into Maths in Early Childhood classrooms. In spite of that, it is obvious that it is at these ages when the learning of mathematics acts as a…
Control Networks and Neuromodulators of Early Development
ERIC Educational Resources Information Center
Posner, Michael I.; Rothbart, Mary K.; Sheese, Brad E.; Voelker, Pascale
2012-01-01
In adults, most cognitive and emotional self-regulation is carried out by a network of brain regions, including the anterior cingulate, insula, and areas of the basal ganglia, related to executive attention. We propose that during infancy, control systems depend primarily upon a brain network involved in orienting to sensory events that includes…
Typical and atypical brain development: a review of neuroimaging studies
Dennis, Emily L.; Thompson, Paul M.
2013-01-01
In the course of development, the brain undergoes a remarkable process of restructuring as it adapts to the environment and becomes more efficient in processing information. A variety of brain imaging methods can be used to probe how anatomy, connectivity, and function change in the developing brain. Here we review recent discoveries regarding these brain changes in both typically developing individuals and individuals with neurodevelopmental disorders. We begin with typical development, summarizing research on changes in regional brain volume and tissue density, cortical thickness, white matter integrity, and functional connectivity. Space limits preclude the coverage of all neurodevelopmental disorders; instead, we cover a representative selection of studies examining neural correlates of autism, attention deficit/hyperactivity disorder, Fragile X, 22q11.2 deletion syndrome, Williams syndrome, Down syndrome, and Turner syndrome. Where possible, we focus on studies that identify an age by diagnosis interaction, suggesting an altered developmental trajectory. The studies we review generally cover the developmental period from infancy to early adulthood. Great progress has been made over the last 20 years in mapping how the brain matures with MR technology. With ever-improving technology, we expect this progress to accelerate, offering a deeper understanding of brain development, and more effective interventions for neurodevelopmental disorders. PMID:24174907
Typical and atypical brain development: a review of neuroimaging studies.
Dennis, Emily L; Thompson, Paul M
2013-09-01
In the course of development, the brain undergoes a remarkable process of restructuring as it adapts to the environment and becomes more efficient in processing information. A variety of brain imaging methods can be used to probe how anatomy, connectivity, and function change in the developing brain. Here we review recent discoveries regarding these brain changes in both typically developing individuals and individuals with neurodevelopmental disorders. We begin with typical development, summarizing research on changes in regional brain volume and tissue density, cortical thickness, white matter integrity, and functional connectivity. Space limits preclude the coverage of all neurodevelopmental disorders; instead, we cover a representative selection of studies examining neural correlates of autism, attention deficit/hyperactivity disorder, Fragile X, 22q11.2 deletion syndrome, Williams syndrome, Down syndrome, and Turner syndrome. Where possible, we focus on studies that identify an age by diagnosis interaction, suggesting an altered developmental trajectory. The studies we review generally cover the developmental period from infancy to early adulthood. Great progress has been made over the last 20 years in mapping how the brain matures with MR technology. With ever-improving technology, we expect this progress to accelerate, offering a deeper understanding of brain development, and more effective interventions for neurodevelopmental disorders.
Paterson, Sarah J.; Heim, Sabine; Friedman, Jennifer Thomas; Choudhury, Naseem; Benasich, April A.
2007-01-01
Recent advances in cognitive neuroscience have allowed us to begin investigating the development of both structure and function in the infant brain. However, despite the rapid evolution of technology, surprisingly few studies have examined the intersection between brain and behaviour over the first years of life. Even fewer have done so in the context of a particular research question. This paper aims to provide an overview of four domains that have been studied using techniques amenable to elucidating the brain/behaviour interface: language, face processing, object permanence, and joint attention, with particular emphasis on studies focusing on early development. The importance of the unique role of development and the interplay between structure and function is stressed throughout. It is hoped that this review will serve as a catalyst for further thinking about the substantial gaps in our understanding of the relationship between brain and behaviour across development. Further, our aim is to provide ideas about candidate brain areas that are likely to be implicated in particular behaviours or cognitive domains. PMID:16890291
Lopez-Atalaya, Jose P; Askew, Katharine E; Sierra, Amanda; Gomez-Nicola, Diego
2018-06-01
Microglia and non-parenchymal macrophages located in the perivascular space, the meninges and the choroid plexus are independent immune populations that play vital roles in brain development, homeostasis, and tissue healing. Resident macrophages account for a significant proportion of cells in the brain and their density remains stable throughout the lifespan thanks to constant turnover. Microglia develop from yolk sac progenitors, later evolving through intermediate progenitors in a fine-tuned process in which intrinsic factors and external stimuli combine to progressively sculpt their cell type-specific transcriptional profiles. Recent evidence demonstrates that non-parenchymal macrophages are also generated during early embryonic development. In recent years, the development of powerful fate mapping approaches combined with novel genomic and transcriptomic methodologies have greatly expanded our understanding of how brain macrophages develop and acquire specialized functions, and how cell population dynamics are regulated. Here, we review the transcription factors, epigenetic remodeling, and signaling pathways orchestrating the embryonic development of microglia and non-parenchymal macrophages. Next, we describe the dynamics of the macrophage populations of the brain and discuss the role of progenitor cells, to gain a better understanding of their functions in the healthy and diseased brain. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 78: 561-579, 2018. © 2017 The Authors Developmental Neurobiology Published by Wiley Periodicals, Inc.
Children's Executive Functions: Are They Poorer after Very Early Brain Insult
ERIC Educational Resources Information Center
Anderson, Vicki; Spencer-Smith, Megan; Coleman, Lee; Anderson, Peter; Williams, Jackie; Greenham, Mardee; Leventer, Richard J.; Jacobs, Rani
2010-01-01
Traditionally early brain insult (EBI) has been considered to have better outcome than later injury, consistent with the notion that the young brain is flexible and able to reorganize. Recent research findings question this view, suggesting that EBI might lead to poorer outcome than brain insult at any other age. Exploring this early vulnerability…
A Starring Role for Microglia in Brain Sex Differences
Lenz, Kathryn M.; McCarthy, Margaret M.
2017-01-01
Microglia, the resident innate immune cells in the brain, have long been understood to be crucial to maintenance in the nervous system, by clearing debris, monitoring for infiltration of infectious agents, and mediating the brain’s inflammatory and repair response to traumatic injury, stroke, or neurodegeneration. A wave of new research has shown that microglia are also active players in many basic processes in the healthy brain, including cell proliferation, synaptic connectivity, and physiology. Microglia, both in their capacity as phagocytic cells and via secretion of many neuroactive molecules, including cytokines and growth factors, play a central role in early brain development, including sexual differentiation of the brain. In this review, we present the vast roles microglia play in normal brain development and how perturbations in the normal neuroimmune environment during development may contribute to the etiology of brain-based disorders. There are notable differences between microglia and neuroimmune signaling in the male and female brain throughout the life span, and these differences may contribute to the vast differences in the incidence of neuropsychiatric and neurological disorders between males and females. PMID:24871624
Downregulation of ribosome biogenesis during early forebrain development
Chau, Kevin F; Shannon, Morgan L; Fame, Ryann M; Fonseca, Erin; Mullan, Hillary; Johnson, Matthew B; Sendamarai, Anoop K; Springel, Mark W; Laurent, Benoit
2018-01-01
Forebrain precursor cells are dynamic during early brain development, yet the underlying molecular changes remain elusive. We observed major differences in transcriptional signatures of precursor cells from mouse forebrain at embryonic days E8.5 vs. E10.5 (before vs. after neural tube closure). Genes encoding protein biosynthetic machinery were strongly downregulated at E10.5. This was matched by decreases in ribosome biogenesis and protein synthesis, together with age-related changes in proteomic content of the adjacent fluids. Notably, c-MYC expression and mTOR pathway signaling were also decreased at E10.5, providing potential drivers for the effects on ribosome biogenesis and protein synthesis. Interference with c-MYC at E8.5 prematurely decreased ribosome biogenesis, while persistent c-MYC expression in cortical progenitors increased transcription of protein biosynthetic machinery and enhanced ribosome biogenesis, as well as enhanced progenitor proliferation leading to subsequent macrocephaly. These findings indicate large, coordinated changes in molecular machinery of forebrain precursors during early brain development. PMID:29745900
ERIC Educational Resources Information Center
Mehta, Mitul A.; Golembo, Nicole I.; Nosarti, Chiara; Colvert, Emma; Mota, Ashley; Williams, Steven C. R.; Rutter, Michael; Sonuga-Barke, Edmund J. S.
2009-01-01
The adoption into the UK of children who have been reared in severely deprived conditions provides an opportunity to study possible association between very early negative experiences and subsequent brain development. This cross-sectional study was a pilot for a planned larger study quantifying the effects of early deprivation on later brain…
Early Childhood Intervention: Shaping the Future for Children with Special Needs and Their Families
ERIC Educational Resources Information Center
Eidelman, Steven, Ed.; Kaczmarek, Louise A., Ed.; Maude, Susan P., Ed.
2011-01-01
This eye-opening set looks at young children with special needs, their families, and the laws, policies, programs, and services designed to help them. It is scientifically known that early childhood is a time of significant brain development. That makes it especially crucial that children with special needs be recognized early so that appropriate…
ERIC Educational Resources Information Center
Kilburn, M. Rebecca; Karoly, Lynn A.
2008-01-01
Scientific discoveries over the past two decades have transformed the way in which researchers, policymakers, and the public think about early childhood. For example, recent research in brain science has provided a biological basis for prevailing theories about early child development, and cost-benefit analysis has reoriented some of the…
Güiza, Fabian; Depreitere, Bart; Piper, Ian; Citerio, Giuseppe; Jorens, Philippe G; Maas, Andrew; Schuhmann, Martin U; Lo, Tsz-Yan Milly; Donald, Rob; Jones, Patricia; Maier, Gottlieb; Van den Berghe, Greet; Meyfroidt, Geert
2017-03-01
A model for early detection of episodes of increased intracranial pressure in traumatic brain injury patients has been previously developed and validated based on retrospective adult patient data from the multicenter Brain-IT database. The purpose of the present study is to validate this early detection model in different cohorts of recently treated adult and pediatric traumatic brain injury patients. Prognostic modeling. Noninterventional, observational, retrospective study. The adult validation cohort comprised recent traumatic brain injury patients from San Gerardo Hospital in Monza (n = 50), Leuven University Hospital (n = 26), Antwerp University Hospital (n = 19), Tübingen University Hospital (n = 18), and Southern General Hospital in Glasgow (n = 8). The pediatric validation cohort comprised patients from neurosurgical and intensive care centers in Edinburgh and Newcastle (n = 79). None. The model's performance was evaluated with respect to discrimination, calibration, overall performance, and clinical usefulness. In the recent adult validation cohort, the model retained excellent performance as in the original study. In the pediatric validation cohort, the model retained good discrimination and a positive net benefit, albeit with a performance drop in the remaining criteria. The obtained external validation results confirm the robustness of the model to predict future increased intracranial pressure events 30 minutes in advance, in adult and pediatric traumatic brain injury patients. These results are a large step toward an early warning system for increased intracranial pressure that can be generally applied. Furthermore, the sparseness of this model that uses only two routinely monitored signals as inputs (intracranial pressure and mean arterial blood pressure) is an additional asset.
Miller, Jeff; Schwarz, Wolf
2014-02-01
Neuroscientific studies have shown that brain activity correlated with a decision to move can be observed before a person reports being consciously aware of having made that decision (e.g., Libet, Gleason, Wright, & Pearl, 1983; Soon, Brass, Heinze, & Haynes, 2008). Given that a later event (i.e., conscious awareness) cannot cause an earlier one (i.e., decision-related brain activity), such results have been interpreted as evidence that decisions are made unconsciously (e.g., Libet, 1985). We argue that this interpretation depends upon an all-or-none view of consciousness, and we offer an alternative interpretation of the early decision-related brain activity based on models in which conscious awareness of the decision to move develops gradually up to the level of a reporting criterion. Under this interpretation, the early brain activity reflects sub-criterion levels of awareness rather than complete absence of awareness and thus does not suggest that decisions are made unconsciously. Copyright © 2013 Elsevier Inc. All rights reserved.
Hrabovszky, Zoltan; Hutson, John M
2002-11-01
Psychosexual development, gender assignment and surgical treatment in patients with intersex are controversial issues in the medical literature. Some groups are of the opinion that gender identity and sexual orientation are determined prenatally secondary to the fetal hormonal environment causing irreversible development of the nervous system. We reviewed the evidence in animal and human studies to determine the possible role of early postnatal androgen production in gender development. An extensive literature review was performed of data from animal experiments and human studies. RESULTS Many animal studies show that adding or removing hormonal stimulus in early postnatal life can profoundly alter gender behavior of the adult animal. Human case studies show that late intervention is unable to reverse gender orientation from male to female. Most studies have not permitted testing of whether early gender assignment and treatment as female with suppression/ablation of postnatal androgen production leads to improved concordance of the gender identity and sex of rearing. Animal studies support a role for postnatal androgens in brain/behavior development with human studies neither completely supportive nor antagonistic. Therefore, gender assignment in infants with intersex should be made with the possibility in mind that postnatal testicular hormones at ages 1 to 6 months may affect gender identity. A case-control study is required to test the hypothesis that postnatal androgen exposure may convert ambisexual brain functions to committed male behavior patterns.
Cortical gyrification is abnormal in children with prenatal alcohol exposure.
Hendrickson, Timothy J; Mueller, Bryon A; Sowell, Elizabeth R; Mattson, Sarah N; Coles, Claire D; Kable, Julie A; Jones, Kenneth L; Boys, Christopher J; Lim, Kelvin O; Riley, Edward P; Wozniak, Jeffrey R
2017-01-01
Prenatal alcohol exposure (PAE) adversely affects early brain development. Previous studies have shown a wide range of structural and functional abnormalities in children and adolescents with PAE. The current study adds to the existing literature specifically on cortical development by examining cortical gyrification in a large sample of children with PAE compared to controls. Relationships between cortical development and intellectual functioning are also examined. Included were 92 children with PAE and 83 controls ages 9-16 from four sites in the Collaborative Initiative on FASD (CIFASD). All PAE participants had documented heavy PAE. All underwent a formal evaluation of physical anomalies and dysmorphic facial features. MRI data were collected using modified matched protocols on three platforms (Siemens, GE, and Philips). Cortical gyrification was examined using a semi-automated procedure. Whole brain group comparisons using Monte Carlo z-simulation for multiple comparisons showed significantly lower cortical gyrification across a large proportion of the cerebral cortex amongst PAE compared to controls. Whole brain comparisons and ROI based analyses showed strong positive correlations between cortical gyrification and IQ (i.e. less developed cortex was associated with lower IQ). Abnormalities in cortical development were seen across the brain in children with PAE compared to controls. Cortical gyrification and IQ were strongly correlated, suggesting that examining mechanisms by which alcohol disrupts cortical formation may yield clinically relevant insights and potential directions for early intervention.
Mammalian brain development and our grandmothering life history.
Hawkes, Kristen; Finlay, Barbara L
2018-05-02
Among mammals, including humans, adult brain size and the relative size of brain components depend precisely on the duration of a highly regular process of neural development. Much wider variation is seen in rates of body growth and the state of neural maturation at life history events like birth and weaning. Large brains result from slow maturation, which in humans is accompanied by weaning early with respect to both neural maturation and longevity. The grandmother hypothesis proposes this distinctive combination of life history features evolved as ancestral populations began to depend on foods that just weaned juveniles couldn't handle. Here we trace possible reciprocal connections between brain development and life history, highlighting the resulting extended neural plasticity in a wider cognitive ecology of allomaternal care that distinguishes human ontogeny with consequences for other peculiarities of our lineage. Copyright © 2018 Elsevier Inc. All rights reserved.
Normal Brain-Skull Development with Hybrid Deformable VR Models Simulation.
Jin, Jing; De Ribaupierre, Sandrine; Eagleson, Roy
2016-01-01
This paper describes a simulation framework for a clinical application involving skull-brain co-development in infants, leading to a platform for craniosynostosis modeling. Craniosynostosis occurs when one or more sutures are fused early in life, resulting in an abnormal skull shape. Surgery is required to reopen the suture and reduce intracranial pressure, but is difficult without any predictive model to assist surgical planning. We aim to study normal brain-skull growth by computer simulation, which requires a head model and appropriate mathematical methods for brain and skull growth respectively. On the basis of our previous model, we further specified suture model into fibrous and cartilaginous sutures and develop algorithm for skull extension. We evaluate the resulting simulation by comparison with datasets of cases and normal growth.
[Associative Learning between Orientation and Color in Early Visual Areas].
Amano, Kaoru; Shibata, Kazuhisa; Kawato, Mitsuo; Sasaki, Yuka; Watanabe, Takeo
2017-08-01
Associative learning is an essential neural phenomenon where the contingency of different items increases after training. Although associative learning has been found to occur in many brain regions, there is no clear evidence that associative learning of visual features occurs in early visual areas. Here, we developed an associative decoded functional magnetic resonance imaging (fMRI) neurofeedback (A-DecNef) to determine whether associative learning of color and orientation can be induced in early visual areas. During the three days' training, A-DecNef induced fMRI signal patterns that corresponded to a specific target color (red) mostly in early visual areas while a vertical achromatic grating was simultaneously, physically presented to participants. Consequently, participants' perception of "red" was significantly more frequently than that of "green" in an achromatic vertical grating. This effect was also observed 3 to 5 months after training. These results suggest that long-term associative learning of two different visual features such as color and orientation, was induced most likely in early visual areas. This newly extended technique that induces associative learning may be used as an important tool for understanding and modifying brain function, since associations are fundamental and ubiquitous with respect to brain function.
Falzone, Nadia; Ackerman, Nicole L; Rosales, Liset de la Fuente; Bernal, Mario A; Liu, Xiaoxuan; Peeters, Sarah Gja; Soto, Manuel Sarmiento; Corroyer-Dulmont, Aurélien; Bernaudin, Myriam; Grimoin, Elisa; Touzani, Omar; Sibson, Nicola R; Vallis, Katherine A
2018-01-01
Brain metastases develop frequently in patients with breast cancer, and present a pressing therapeutic challenge. Expression of vascular cell adhesion molecule 1 (VCAM-1) is upregulated on brain endothelial cells during the early stages of metastasis and provides a target for the detection and treatment of early brain metastases. The aim of this study was to use a model of early brain metastasis to evaluate the efficacy of α-emitting radionuclides, 149 Tb, 211 At, 212 Pb, 213 Bi and 225 Ac; β-emitting radionuclides, 90 Y, 161 Tb and 177 Lu; and Auger electron (AE)-emitters 67 Ga, 89 Zr, 111 In and 124 I, for targeted radionuclide therapy (TRT). Histologic sections and two photon microscopy of mouse brain parenchyma were used to inform a cylindrical vessel geometry using the Geant4 general purpose Monte Carlo (MC) toolkit with the Geant4-DNA low energy physics models. Energy deposition was evaluated as a radial function and the resulting phase spaces were superimposed on a DNA model to estimate double-strand break (DSB) yields for representative β- and α-emitters, 177 Lu and 212 Pb. Relative biological effectiveness (RBE) values were determined by only evaluating DNA damage due to physical interactions. 177 Lu produced 2.69 ± 0.08 DSB per GbpGy, without significant variation from the lumen of the vessel to a radius of 100 µm. The DSB yield of 212 Pb included two local maxima produced by the 6.1 MeV and 8.8 MeV α-emissions from decay products, 212 Bi and 212 Po, with yields of 7.64 ± 0.12 and 9.15 ± 0.24 per GbpGy, respectively. Given its higher DSB yield 212 Pb may be more effective for short range targeting of early micrometastatic lesions than 177 Lu. MC simulation of a model of early brain metastases provides invaluable insight into the potential efficacy of α-, β- and AE-emitting radionuclides for TRT. 212 Pb, which has the attributes of a theranostic radionuclide since it can be used for SPECT imaging, showed a favorable dose profile and RBE.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Connor, D.M.; Miller, L.; Benveniste, H.
Our understanding of early development in Alzheimer's disease (AD) is clouded by the scale at which the disease progresses; amyloid beta (A{beta}) plaques, a hallmark feature of AD, are small ({approx} 50 {micro}m) and low contrast in diagnostic clinical imaging techniques. Diffraction enhanced imaging (DEI), a phase contrast x-ray imaging technique, has greater soft tissue contrast than conventional radiography and generates higher resolution images than magnetic resonance microimaging. Thus, in this proof of principle study, DEI in micro-CT mode was performed on the brains of AD-model mice to determine if DEI can visualize A{beta} plaques. Results revealed small nodules inmore » the cortex and hippocampus of the brain. Histology confirmed that the features seen in the DEI images of the brain were A{beta} plaques. Several anatomical structures, including hippocampal subregions and white matter tracks, were also observed. Thus, DEI has strong promise in early diagnosis of AD, as well as general studies of the mouse brain.« less
Cocaine-Induced Neurodevelopmental Deficits and Underlying Mechanisms
Martin, Melissa M.; Graham, Devon L.; McCarthy, Deirdre M.; Bhide, Pradeep G.; Stanwood, Gregg D.
2017-01-01
Exposure to drugs early in life has complex and long-lasting implications for brain structure and function. This review summarizes work to date on the immediate and long-term effects of prenatal exposure to cocaine. In utero cocaine exposure produces disruptions in brain monoamines, particularly dopamine, during sensitive periods of brain development, and leads to permanent changes in specific brain circuits, molecules, and behavior. Here, we integrate clinical studies and significance with mechanistic preclinical studies, to define our current knowledge base and identify gaps for future investigation. PMID:27345015
Brain and bone abnormalities of thanatophoric dwarfism.
Miller, Elka; Blaser, Susan; Shannon, Patrick; Widjaja, Elysa
2009-01-01
The purpose of this article is to present the imaging findings of skeletal and brain abnormalities in thanatophoric dwarfism, a lethal form of dysplastic dwarfism. The bony abnormalities associated with thanatophoric dwarfism include marked shortening of the tubular bones and ribs. Abnormal temporal lobe development is a common associated feature and can be visualized as early as the second trimester. It is important to assess the brains of fetuses with suspected thanatophoric dwarfism because the presence of associated brain malformations can assist in the antenatal diagnosis of thanatophoric dwarfism.
Social Origins of Developmental Risk for Mental and Physical Illness.
Cameron, Judy L; Eagleson, Kathie L; Fox, Nathan A; Hensch, Takao K; Levitt, Pat
2017-11-08
Adversity in early childhood exerts an enduring impact on mental and physical health, academic achievement, lifetime productivity, and the probability of interfacing with the criminal justice system. More science is needed to understand how the brain is affected by early life stress (ELS), which produces excessive activation of stress response systems broadly throughout the child's body (toxic stress). Our research examines the importance of sex, timing and type of stress exposure, and critical periods for intervention in various brain systems across species. Neglect (the absence of sensitive and responsive caregiving) or disrupted interaction with offspring induces robust, lasting consequences in mice, monkeys, and humans. Complementary assessment of internalizing disorders and brain imaging in children suggests that early adversity can interfere with white matter development in key brain regions, which may increase risk for emotional difficulties in the long term. Neural circuits that are most plastic during ELS exposure in monkeys sustain the greatest change in gene expression, offering a mechanism whereby stress timing might lead to markedly different long-term behaviors. Rodent models reveal that disrupted maternal-infant interactions yield metabolic and behavioral outcomes often differing by sex. Moreover, ELS may further accelerate or delay critical periods of development, which reflect GABA circuit maturation, BDNF, and circadian Clock genes. Such factors are associated with several mental disorders and may contribute to a premature closure of plastic windows for intervention following ELS. Together, complementary cross-species studies are elucidating principles of adaptation to adversity in early childhood with molecular, cellular, and whole organism resolution. Copyright © 2017 the authors 0270-6474/17/3710783-09$15.00/0.
The Neurobiology of Attachment to Nurturing and Abusive Caregivers
Sullivan, Regina M.
2013-01-01
Decades of research have shown that childhood experiences interact with our genetics to change the structure and function of the brain. Within the range of normal experiences, this system enables the brain to be modified during development to adapt to various environments and cultures. Experiences with and attachment to the caregiver appear particularly important, and recent research suggests this may be due, in part, to the attachment circuitry within the brain. Children have brain circuitry to ensure attachment to their caregivers. Attachment depends on the offspring learning about the caregiver in a process that begins prenatally and continues through most of early life. This attachment serves two basic functions. First, attachment ensures the infant remain in the proximity of the caregiver to procure resources for survival and protection. Second, attachment “quality programs” the brain. This programming impacts immediate behaviors, as well as behaviors that emerge later in development. Animal research has uncovered segments of the attachment circuitry within the brain and has highlighted rapid, robust learning to support this attachment. A child attaches to the caregiver regardless of the quality of care received, even if the caregiver is abusive and neglectful. While a neural system that ensures attachment regardless of the quality of care has immediate benefits, this attachment comes with a high cost. Traumatic experiences interact with genetics to change the structure and function of the brain, compromising emotional and cognitive development and initiating a pathway to pathology. Neurobiological research on animals suggests that trauma during attachment is processed differently by the brain, with maternal presence dramatically attenuating the fear center of the brain (amygdala). Thus, the immaturity of the brain combined with the unique processing of trauma may underlie the enduring effects of abuse, which remain largely hidden in early life but emerge as mental health issues in periadolescence. PMID:24049190
PHONATION TAKES PRECEDENCE IN DEVELOPMENT AS WELL AS EVOLUTION OF LANGUAGE
Oller, D. Kimbrough
2014-01-01
Early development of vocalization in humans is characterized by emerging control of phonation, rather than of prosody or supraglottal articulation. This fact offers an opportunity to the authors of the target article to enrich their characterization of the evolution of differential brain mechanisms in human and non-human primates. Phonation, I suggest, is the initial target of human-specific brain changes in sound-making capability upon which language is founded. PMID:25514957
Rijken, Marcus J; de Wit, Merel Charlotte; Mulder, Eduard J H; Kiricharoen, Suporn; Karunkonkowit, Noaeni; Paw, Tamalar; Visser, Gerard H A; McGready, Rose; Nosten, François H; Pistorius, Lourens R
2012-07-02
Malaria in pregnancy has a negative impact on foetal growth, but it is not known whether this also affects the foetal nervous system. The aim of this study was to examine the effects of malaria on foetal cortex development by three-dimensional ultrasound. Brain images were acquired using a portable ultrasound machine and a 3D ultrasound transducer. All recordings were analysed, blinded to clinical data, using the 4D view software package. The foetal supra-tentorial brain volume was determined and cortical development was qualitatively followed by scoring the appearance and development of six sulci. Multilevel analysis was used to study brain volume and cortical development in individual foetuses. Cortical grading was possible in 161 out of 223 (72%) serial foetal brain images in pregnant women living in a malaria endemic area. There was no difference between foetal cortical development or brain volumes at any time in pregnancy between women with immediately treated malaria infections and non-infected pregnancies. The percentage of images that could be graded was similar to other neuro-sonographic studies. Maternal malaria does not have a gross effect on foetal brain development, at least in this population, which had access to early detection and effective treatment of malaria.
Padilla, Nelly; Eklöf, Eva; Mårtensson, Gustaf E; Bölte, Sven; Lagercrantz, Hugo; Ådén, Ulrika
2017-02-01
Preterm infants face an increased risk of autism spectrum disorder (ASD). The relationship between autism during childhood and early brain development remains unexplored. We studied 84 preterm children born at <27 weeks of gestation, who underwent neonatal magnetic resonance imaging (MRI) at term and were screened for ASD at 6.5 years. Full-scale intelligence quotient was measured and neonatal morbidities were recorded. Structural brain morphometric studies were performed in 33 infants with high-quality MRI and no evidence of focal brain lesions. Twenty-three (27.4%) of the children tested ASD positive and 61 (72.6%) tested ASD negative. The ASD-positive group had a significantly higher frequency of neonatal complications than the ASD-negative group. In the subgroup of 33 children, the ASD infants had reduced volumes in the temporal, occipital, insular, and limbic regions and in the brain areas involved in social/behavior and salience integration. This study shows that the neonatal MRI scans of extremely preterm children, subsequently diagnosed with ASD at 6.5 years, showed brain structural alterations, localized in the regions that play a key role in the core features of autism. Early detection of these structural alterations may allow the early identification and intervention of children at risk of ASD. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
Snowdon, D A; Greiner, L H; Markesbery, W R
2000-04-01
Findings from the Nun Study indicate that low linguistic ability in early life has a strong association with dementia and premature death in late life. In the present study, we investigated the relationship of linguistic ability in early life to the neuropathology of Alzheimer's disease and cerebrovascular disease. The analyses were done on a subset of 74 participants in the Nun Study for whom we had handwritten autobiographies completed some time between the ages of 19 and 37 (mean = 23 years). An average of 62 years after writing the autobiographies, when the participants were 78 to 97 years old, they died and their brains were removed for our neuropathologic studies. Linguistic ability in early life was measured by the idea (proposition) density of the autobiographies, i.e., a standard measure of the content of ideas in text samples. Idea density scores from early life had strong inverse correlations with the severity of Alzheimer's disease pathology in the neocortex: Correlations between idea density scores and neurofibrillary tangle counts were -0.59 for the frontal lobe, -0.48 for the temporal lobe, and -0.49 for the parietal lobe (all p values < 0.0001). Idea density scores were unrelated to the severity of atherosclerosis of the major arteries at the base of the brain and to the presence of lacunar and large brain infarcts. Low linguistic ability in early life may reflect suboptimal neurological and cognitive development, which might increase susceptibility to the development of Alzheimer's disease pathology in late life.
Bao, Ai-Min; Swaab, Dick F
2011-04-01
During the intrauterine period a testosterone surge masculinizes the fetal brain, whereas the absence of such a surge results in a feminine brain. As sexual differentiation of the brain takes place at a much later stage in development than sexual differentiation of the genitals, these two processes can be influenced independently of each other. Sex differences in cognition, gender identity (an individual's perception of their own sexual identity), sexual orientation (heterosexuality, homosexuality or bisexuality), and the risks of developing neuropsychiatric disorders are programmed into our brain during early development. There is no evidence that one's postnatal social environment plays a crucial role in gender identity or sexual orientation. We discuss the relationships between structural and functional sex differences of various brain areas and the way they change along with any changes in the supply of sex hormones on the one hand and sex differences in behavior in health and disease on the other. Copyright © 2011 Elsevier Inc. All rights reserved.
Docosahexaenoic acid (DHA), a fundamental fatty acid for the brain: New dietary sources.
Echeverría, Francisca; Valenzuela, Rodrigo; Catalina Hernandez-Rodas, María; Valenzuela, Alfonso
2017-09-01
Docosahexaenoic acid (C22: 6n-3, DHA) is a long-chain polyunsaturated fatty acid of marine origin fundamental for the formation and function of the nervous system, particularly the brain and the retina of humans. It has been proposed a remarkable role of DHA during human evolution, mainly on the growth and development of the brain. Currently, DHA is considered a critical nutrient during pregnancy and breastfeeding due their active participation in the development of the nervous system in early life. DHA and specifically one of its derivatives known as neuroprotectin D-1 (NPD-1), has neuroprotective properties against brain aging, neurodegenerative diseases and injury caused after brain ischemia-reperfusion episodes. This paper discusses the importance of DHA in the human brain given its relevance in the development of the tissue and as neuroprotective agent. It is also included a critical view about the ways to supply this noble fatty acid to the population. Copyright © 2017 Elsevier Ltd. All rights reserved.
Advancing Early Childhood Development: from Science to Scale 1
Black, Maureen M; Walker, Susan P; Fernald, Lia C H; Andersen, Christopher T; DiGirolamo, Ann M; Lu, Chunling; McCoy, Dana C; Fink, Günther; Shawar, Yusra R; Shiffman, Prof Jeremy; Devercelli, Amanda E; Wodon, Quentin T; Vargas-Barón, Emily; Grantham-McGregor, Sally
2018-01-01
Early childhood development programmes vary in coordination and quality, with inadequate and inequitable access, especially for children younger than 3 years. New estimates, based on proxy measures of stunting and poverty, indicate that 250 million children (43%) younger than 5 years in low-income and middle-income countries are at risk of not reaching their developmental potential. There is therefore an urgent need to increase multisectoral coverage of quality programming that incorporates health, nutrition, security and safety, responsive caregiving, and early learning. Equitable early childhood policies and programmes are crucial for meeting Sustainable Development Goals, and for children to develop the intellectual skills, creativity, and wellbeing required to become healthy and productive adults. In this paper, the first in a three part Series on early childhood development, we examine recent scientific progress and global commitments to early childhood development. Research, programmes, and policies have advanced substantially since 2000, with new neuroscientific evidence linking early adversity and nurturing care with brain development and function throughout the life course. PMID:27717614
Developmental Outcomes after Early Prefrontal Cortex Damage
ERIC Educational Resources Information Center
Eslinger, Paul J.; Flaherty-Craig, Claire V.; Benton, Arthur L.
2004-01-01
The neuropsychological bases of cognitive, social, and moral development are minimally understood, with a seemingly wide chasm between developmental theories and brain maturation models. As one approach to bridging ideas in these areas, we review 10 cases of early prefrontal cortex damage from the clinical literature, highlighting overall clinical…
Developments in Neurofeedback: Should Health Educators Be Paying Attention?
ERIC Educational Resources Information Center
Cleary, Michael J.
2011-01-01
Since the early 1970s, neuroscientists recognized that it was possible for patients to re-regulate brain wave activity. Much of this early work focused on helping persons with epilepsy control their seizures and was later extended toward helping children with attention deficit hyperactivity disorder (ADHD) with concentration. This brainwave…
Alonso, Maria I; Lamus, Francisco; Carnicero, Estela; Moro, Jose A; de la Mano, Anibal; Fernández, Jose M F; Desmond, Mary E; Gato, Angel
2017-01-01
Neurogenesis is a very intensive process during early embryonic brain development, becoming dramatically restricted in the adult brain in terms of extension and intensity. We have previously demonstrated the key role of embryonic cerebrospinal fluid (CSF) in developing brain neurogenic activity. We also showed that cultured adult brain neural stem cells (NSCs) remain competent when responding to the neurogenic influence of embryonic CSF. However, adult CSF loses its neurogenic inductive properties. Here, by means of an organotypic culture of adult mouse brain sections, we show that local administration of embryonic CSF in the subventricular zone (SVZ) niche is able to trigger a neurogenic program in NSCs. This leads to a significant increase in the number of non-differentiated NSCs, and also in the number of new neurons which show normal migration, differentiation and maturation. These new data reveal that embryonic CSF activates adult brain NSCs, supporting the previous idea that it contains key instructive components which could be useful in adult brain neuroregenerative strategies.
Maternal-fetal unit interactions and eutherian neocortical development and evolution
Montiel, Juan F.; Kaune, Heidy; Maliqueo, Manuel
2013-01-01
The conserved brain design that primates inherited from early mammals differs from the variable adult brain size and species-specific brain dominances observed across mammals. This variability relies on the emergence of specialized cerebral cortical regions and sub-compartments, triggering an increase in brain size, areal interconnectivity and histological complexity that ultimately lies on the activation of developmental programs. Structural placental features are not well correlated with brain enlargement; however, several endocrine pathways could be tuned with the activation of neuronal progenitors in the proliferative neocortical compartments. In this article, we reviewed some mechanisms of eutherians maternal–fetal unit interactions associated with brain development and evolution. We propose a hypothesis of brain evolution where proliferative compartments in primates become activated by “non-classical” endocrine placental signals participating in different steps of corticogenesis. Changes in the inner placental structure, along with placenta endocrine stimuli over the cortical proliferative activity would allow mammalian brain enlargement with a concomitant shorter gestation span, as an evolutionary strategy to escape from parent-offspring conflict. PMID:23882189
Alonso, Maria I.; Lamus, Francisco; Carnicero, Estela; Moro, Jose A.; de la Mano, Anibal; Fernández, Jose M. F.; Desmond, Mary E.; Gato, Angel
2017-01-01
Neurogenesis is a very intensive process during early embryonic brain development, becoming dramatically restricted in the adult brain in terms of extension and intensity. We have previously demonstrated the key role of embryonic cerebrospinal fluid (CSF) in developing brain neurogenic activity. We also showed that cultured adult brain neural stem cells (NSCs) remain competent when responding to the neurogenic influence of embryonic CSF. However, adult CSF loses its neurogenic inductive properties. Here, by means of an organotypic culture of adult mouse brain sections, we show that local administration of embryonic CSF in the subventricular zone (SVZ) niche is able to trigger a neurogenic program in NSCs. This leads to a significant increase in the number of non-differentiated NSCs, and also in the number of new neurons which show normal migration, differentiation and maturation. These new data reveal that embryonic CSF activates adult brain NSCs, supporting the previous idea that it contains key instructive components which could be useful in adult brain neuroregenerative strategies. PMID:29311854
Economic, neurobiological, and behavioral perspectives on building America’s future workforce
Knudsen, Eric I.; Heckman, James J.; Cameron, Judy L.; Shonkoff, Jack P.
2006-01-01
A growing proportion of the U.S. workforce will have been raised in disadvantaged environments that are associated with relatively high proportions of individuals with diminished cognitive and social skills. A cross-disciplinary examination of research in economics, developmental psychology, and neurobiology reveals a striking convergence on a set of common principles that account for the potent effects of early environment on the capacity for human skill development. Central to these principles are the findings that early experiences have a uniquely powerful influence on the development of cognitive and social skills and on brain architecture and neurochemistry, that both skill development and brain maturation are hierarchical processes in which higher level functions depend on, and build on, lower level functions, and that the capacity for change in the foundations of human skill development and neural circuitry is highest earlier in life and decreases over time. These findings lead to the conclusion that the most efficient strategy for strengthening the future workforce, both economically and neurobiologically, and improving its quality of life is to invest in the environments of disadvantaged children during the early childhood years. PMID:16801553
Lisowska, Anna; Rekik, Islem
2018-06-21
Diagnosis of brain dementia, particularly early mild cognitive impairment (eMCI), is critical for early intervention to prevent the onset of Alzheimer's Disease (AD), where cognitive decline is severe and irreversible. There is a large body of machine-learning based research investigating how dementia alters brain connectivity, mainly using structural (derived from diffusion MRI) and functional (derived from resting-state functional MRI) brain connectomic data. However, how early dementia affects cortical brain connections in morphology remains largely unexplored. To fill this gap, we propose a joint morphological brain multiplexes pairing and mapping strategy for early MCI detection, where a brain multiplex not only encodes the similarity in morphology between pairs of brain regions, but also a pair of brain morphological networks. Experimental results confirm that the proposed framework outperforms in classification accuracy several state-of-the-art methods. More importantly, we unprecedentedly identified most discriminative brain morphological networks between eMCI and NC, which included the paired views derived from maximum principal curvature and the sulcal depth for the left hemisphere and sulcal depth and the average curvature for the right hemisphere. We also identified the most highly correlated morphological brain connections in our cohort, which included the (pericalcarine cortex, insula cortex) on the maximum principal curvature view, (entorhinal cortex, insula cortex) on the mean sulcal depth view, and (entorhinal cortex, pericalcarine cortex) on the mean average curvature view, for both hemispheres. These highly correlated morphological connections might serve as biomarkers for early MCI diagnosis.
Mills, Kathryn L; Goddings, Anne-Lise; Herting, Megan M; Meuwese, Rosa; Blakemore, Sarah-Jayne; Crone, Eveline A; Dahl, Ronald E; Güroğlu, Berna; Raznahan, Armin; Sowell, Elizabeth R; Tamnes, Christian K
2016-11-01
Longitudinal studies including brain measures acquired through magnetic resonance imaging (MRI) have enabled population models of human brain development, crucial for our understanding of typical development as well as neurodevelopmental disorders. Brain development in the first two decades generally involves early cortical grey matter volume (CGMV) increases followed by decreases, and monotonic increases in cerebral white matter volume (CWMV). However, inconsistencies regarding the precise developmental trajectories call into question the comparability of samples. This issue can be addressed by conducting a comprehensive study across multiple datasets from diverse populations. Here, we present replicable models for gross structural brain development between childhood and adulthood (ages 8-30years) by repeating analyses in four separate longitudinal samples (391 participants; 852 scans). In addition, we address how accounting for global measures of cranial/brain size affect these developmental trajectories. First, we found evidence for continued development of both intracranial volume (ICV) and whole brain volume (WBV) through adolescence, albeit following distinct trajectories. Second, our results indicate that CGMV is at its highest in childhood, decreasing steadily through the second decade with deceleration in the third decade, while CWMV increases until mid-to-late adolescence before decelerating. Importantly, we show that accounting for cranial/brain size affects models of regional brain development, particularly with respect to sex differences. Our results increase confidence in our knowledge of the pattern of brain changes during adolescence, reduce concerns about discrepancies across samples, and suggest some best practices for statistical control of cranial volume and brain size in future studies. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.
Perceptual Asymmetry for Chimeric Stimuli in Children with Early Unilateral Brain Damage
ERIC Educational Resources Information Center
Bava, Sunita; Ballantyne, Angela O.; May, Susanne J.; Trauner, Doris A.
2005-01-01
The present study used a chimeric stimuli task to assess the magnitude of the left-hemispace bias in children with congenital unilateral brain damage (n=46) as compared to typically developing matched controls (n=46). As would be expected, controls exhibited a significant left-hemispace bias. In the presence of left hemisphere (LH) damage, the…
ERIC Educational Resources Information Center
Schlotz, Wolff; Jones, Alexander; Phillips, David I. W.; Gale, Catharine R.; Robinson, Sian M.; Godfrey, Keith M.
2010-01-01
Background: Maternal nutrition during pregnancy has been linked with fetal brain development and psychopathology in the offspring. We examined for associations of maternal folate status and dietary intake during pregnancy with brain growth and childhood behavioural difficulties in the offspring. Methods: In a prospective cohort study, maternal red…
Phase Transitions: In the Brain, Socio-Dramatic Play and Meaningful Early Learning
ERIC Educational Resources Information Center
Fromberg, Doris Pronin
2017-01-01
There are similar, non-linear complex dynamical systems that underlie the epigenetic development of young children. This paper discusses the confluence of research on brain functions; a body or research that informs the characteristics of young children's play and imagination; and the ways in which young children acquire fresh perceptions and…
Isaacs, Elizabeth B.
2013-01-01
Nutrition is crucial to the initial development of the central nervous system (CNS), and then to its maintenance, because both depend on dietary intake to supply the elements required to develop and fuel the system. Diet in early life is often seen in the context of “programming” where a stimulus occurring during a vulnerable period can have long-lasting or even lifetime effects on some aspect of the organism's structure or function. Nutrition was first shown to be a programming stimulus for growth, and then for cognitive behavior, in animal studies that were able to employ methods that allowed the demonstration of neural effects of early nutrition. Such research raised the question of whether nutrition could also programme cognition/brain structure in humans. Initial studies of cognitive effects were observational, usually conducted in developing countries where the presence of confounding factors made it difficult to interpret the role of nutrition in the cognitive deficits that were seen. Attributing causality to nutrition required randomized controlled trials (RCTs) and these, often in developed countries, started to appear around 30 years ago. Most demonstrated convincingly that early nutrition could affect subsequent cognition. Until the advent of neuroimaging techniques that allowed in vivo examination of the brain, however, we could determine very little about the neural effects of early diet in humans. The combination of well-designed trials with neuroimaging tools means that we are now able to pose and answer questions that would have seemed impossible only recently. This review discusses various neuroimaging methods that are suitable for use in nutrition studies, while pointing out some of the limitations that they may have. The existing literature is small, but examples of studies that have used these methods are presented. Finally, some considerations that have arisen from previous studies, as well as suggestions for future research, are discussed. PMID:23964224
Neurovascular coupling and energy metabolism in the developing brain
Kozberg, M.; Hillman, E.
2016-01-01
In the adult brain, increases in local neural activity are almost always accompanied by increases in local blood flow. However, many functional imaging studies of the newborn and developing human brain have observed patterns of hemodynamic responses that differ from adult responses. Among the proposed mechanisms for the observed variations is that neurovascular coupling itself is still developing in the perinatal brain. Many of the components thought to be involved in actuating and propagating this hemodynamic response are known to still be developing postnatally, including perivascular cells such as astrocytes and pericytes. Both neural and vascular networks expand and are then selectively pruned over the first year of human life. Additionally, the metabolic demands of the newborn brain are still evolving. These changes are highly likely to affect early postnatal neurovascular coupling, and thus may affect functional imaging signals in this age group. This chapter will discuss the literature relating to neurovascular development. Potential effects of normal and aberrant development of neurovascular coupling on the newborn brain will also be explored, as well as ways to effectively utilize imaging techniques that rely on hemodynamic modulation such as fMRI and NIRS in younger populations. PMID:27130418
Falk, Dean
2016-06-20
Fossil and comparative primatological evidence suggest that alterations in the development of prehistoric hominin infants kindled three consecutive evolutionary-developmental (evo-devo) trends that, ultimately, paved the way for the evolution of the human brain and cognition. In the earliest trend, infants' development of posture and locomotion became delayed because of anatomical changes that accompanied the prolonged evolution of bipedalism. Because modern humans have inherited these changes, our babies are much slower than other primates to reach developmental milestones such as standing, crawling, and walking. The delay in ancestral babies' physical development eventually precipitated an evolutionary reversal in which they became increasing unable to cling independently to their mothers. For the first time in prehistory, babies were, thus, periodically deprived of direct physical contact with their mothers. This prompted the emergence of a second evo-devo trend in which infants sought contact comfort from caregivers using evolved signals, including new ways of crying that are conserved in modern babies. Such signaling stimulated intense reciprocal interactions between prehistoric mothers and infants that seeded the eventual emergence of motherese and, subsequently, protolanguage. The third trend was for an extreme acceleration in brain growth that began prior to the last trimester of gestation and continued through infants' first postnatal year (early "brain spurt"). Conservation of this trend in modern babies explains why human brains reach adult sizes that are over three times those of chimpanzees. The fossil record of hominin cranial capacities together with comparative neuroanatomical data suggest that, around 3 million years ago, early brain spurts began to facilitate an evolutionary trajectory for increasingly large adult brains in association with neurological reorganization. The prehistoric increase in brain size eventually caused parturition to become exceedingly difficult, and this difficulty, known as the "obstetrical dilemma", is likely to constrain the future evolution of brain size and, thus, privilege ongoing evolution in neurological reorganization. In modern babies, the brain spurt is accompanied by formation and tuning (pruning) of neurological connections, and development of dynamic higher-order networks that facilitate acquisition of grammatical language and, later in development, other advanced computational abilities such as musical or mathematical perception and performance. The cumulative evidence suggests that the emergence and refinement of grammatical language was a prime mover of hominin brain evolution.
Sex-related variation in human behavior and the brain
Hines, Melissa
2010-01-01
Male and female fetuses differ in testosterone concentrations beginning as early as week 8 of gestation. This early hormone difference exerts permanent influences on brain development and behavior. Contemporary research shows that hormones are particularly important for the development of sex-typical childhood behavior, including toy choices, which until recently were thought to result solely from sociocultural influences. Prenatal testosterone exposure also appears to influence sexual orientation and gender identity, as well as some, but not all, sex-related cognitive, motor and personality characteristics. Neural mechanisms responsible for these hormone-induced behavioral outcomes are beginning to be identified, and current evidence suggests involvement of the hypothalamus and amygdala, as well as interhemispheric connectivity, and cortical areas involved in visual processing. PMID:20724210
Sex differences in the gut microbiome-brain axis across the lifespan.
Jašarević, Eldin; Morrison, Kathleen E; Bale, Tracy L
2016-02-19
In recent years, the bidirectional communication between the gut microbiome and the brain has emerged as a factor that influences immunity, metabolism, neurodevelopment and behaviour. Cross-talk between the gut and brain begins early in life immediately following the transition from a sterile in utero environment to one that is exposed to a changing and complex microbial milieu over a lifetime. Once established, communication between the gut and brain integrates information from the autonomic and enteric nervous systems, neuroendocrine and neuroimmune signals, and peripheral immune and metabolic signals. Importantly, the composition and functional potential of the gut microbiome undergoes many transitions that parallel dynamic periods of brain development and maturation for which distinct sex differences have been identified. Here, we discuss the sexually dimorphic development, maturation and maintenance of the gut microbiome-brain axis, and the sex differences therein important in disease risk and resilience throughout the lifespan. © 2016 The Author(s).
The Immune System and Developmental Programming of Brain and Behavior
Bilbo, Staci D.; Schwarz, Jaclyn M.
2012-01-01
The brain, endocrine, and immune systems are inextricably linked. Immune molecules have a powerful impact on neuroendocrine function, including hormone-behavior interactions, during health as well as sickness. Similarly, alterations in hormones, such as during stress, can powerfully impact immune function or reactivity. These functional shifts are evolved, adaptive responses that organize changes in behavior and mobilize immune resources, but can also lead to pathology or exacerbate disease if prolonged or exaggerated. The developing brain in particular is exquisitely sensitive to both endogenous and exogenous signals, and increasing evidence suggests the immune system has a critical role in brain development and associated behavioral outcomes for the life of the individual. Indeed, there are associations between many neuropsychiatric disorders and immune dysfunction, with a distinct etiology in neurodevelopment. The goal of this review is to describe the important role of the immune system during brain development, and to discuss some of the many ways in which immune activation during early brain development can affect the later-life outcomes of neural function, immune function, mood and cognition. PMID:22982535
GLUT3 gene expression is critical for embryonic growth, brain development and survival.
Carayannopoulos, Mary O; Xiong, Fuxia; Jensen, Penny; Rios-Galdamez, Yesenia; Huang, Haigen; Lin, Shuo; Devaskar, Sherin U
2014-04-01
Glucose is the primary energy source for eukaryotic cells and the predominant substrate for the brain. GLUT3 is essential for trans-placental glucose transport and highly expressed in the mammalian brain. To further elucidate the role of GLUT3 in embryonic development, we utilized the vertebrate whole animal model system of Danio rerio as a tractable system for defining the cellular and molecular mechanisms altered by impaired glucose transport and metabolism related to perturbed expression of GLUT3. The comparable orthologue of human GLUT3 was identified and the expression of this gene abrogated during early embryonic development. In a dose-dependent manner embryonic brain development was disrupted resulting in a phenotype of aberrant brain organogenesis, associated with embryonic growth restriction and increased cellular apoptosis. Rescue of the morphant phenotype was achieved by providing exogenous GLUT3 mRNA. We conclude that GLUT3 is critically important for brain organogenesis and embryonic growth. Disruption of GLUT3 is responsible for the phenotypic spectrum of embryonic growth restriction to demise and neural apoptosis with microcephaly. Copyright © 2014 Elsevier Inc. All rights reserved.
GLUT3 Gene Expression is Critical for Embryonic Growth, Brain Development and Survival
Carayannopoulos, Mary O.; Xiong, Fuxia; Jensen, Penny; Rios-Galdamez, Yesenia; Huang, Haigen; Lin, Shuo; Devaskar, Sherin U.
2015-01-01
Glucose is the primary energy source for eukaryotic cells and the predominant substrate for the brain. GLUT3 is essential for trans-placental glucose transport and highly expressed in the mammalian brain. To further elucidate the role of GLUT3 in embryonic development, we utilized the vertebrate whole animal model system of Danio rerio as a tractable system for defining the cellular and molecular mechanisms altered by impaired glucose transport and metabolism related to perturbed expression of GLUT3. The comparable orthologue of human GLUT3 was identified and the expression of this gene abrogated during early embryonic development. In a dose-dependent manner embryonic brain development was disrupted resulting in a phenotype of aberrant brain organogenesis, associated with embryonic growth restriction and increased cellular apoptosis. Rescue of the morphant phenotype was achieved by providing exogenous GLUT3 mRNA. We conclude that GLUT3 is critically important for brain organogenesis and embryonic growth. Disruption of GLUT3 is responsible for the phenotypic spectrum of embryonic growth restriction to demise and neural apoptosis with microcephaly. PMID:24529979
Preventing Epilepsy After Traumatic Brain Injury
2009-02-01
treatment of early seizures following TBI, and to compare the efficacy of topiramate to prevent early seizures to the standard of care ( phenytoin ). A...injury (TBI), to determine if topiramate could prevent early seizures better than the current standard of care ( phenytoin ) and to develop a...receive topiramate for three months, and the third, control, arm would receive phenytoin for seven days (current standard of care). EEGs were to
ERIC Educational Resources Information Center
Bigelow, Brian J.
2006-01-01
Recognition of poverty and neglect is very important in formulating a practical diagnosis of children's and adolescent's learning disorders. Early brain development forms the basis of learning, behavior and health over the entire life span. Through accumulated stressors and lack of supports, early poverty undermines competent parenting which then…
Novel Cognitive Paradigms for the Detection of Memory Impairment in Preclinical Alzheimer’s Disease
Loewenstein, David A.; Curiel, Rosie E.; Duara, Ranjan; Buschke, Herman
2017-01-01
In spite of advances in neuroimaging and other brain biomarkers to assess preclinical Alzheimer’s disease (AD), cognitive assessment has relied on traditional memory paradigms developed well over six decades ago. This has led to a growing concern about their effectiveness in the early diagnosis of AD which is essential to develop preventive and early targeted interventions before the occurrence of multisystem brain degeneration. We describe the development of novel tests that are more cognitively challenging, minimize variability in learning strategies, enhance initial acquisition and retrieval using cues, and exploit vulnerabilities in persons with incipient AD such as the susceptibility to proactive semantic interference, and failure to recover from proactive semantic interference. The advantages of various novel memory assessment paradigms are examined as well as how they compare with traditional neuropsychological assessments of memory. Finally, future directions for the development of more effective assessment paradigms are suggested. PMID:29214859
Li, Qian; Guo, Song; Jiang, Xi; Bryk, Jaroslaw; Naumann, Ronald; Enard, Wolfgang; Tomita, Masaru; Sugimoto, Masahiro; Khaitovich, Philipp; Pääbo, Svante
2016-01-01
Whereas all mammals have one glutamate dehydrogenase gene (GLUD1), humans and apes carry an additional gene (GLUD2), which encodes an enzyme with distinct biochemical properties. We inserted a bacterial artificial chromosome containing the human GLUD2 gene into mice and analyzed the resulting changes in the transcriptome and metabolome during postnatal brain development. Effects were most pronounced early postnatally, and predominantly genes involved in neuronal development were affected. Remarkably, the effects in the transgenic mice partially parallel the transcriptome and metabolome differences seen between humans and macaques analyzed. Notably, the introduction of GLUD2 did not affect glutamate levels in mice, consistent with observations in the primates. Instead, the metabolic effects of GLUD2 center on the tricarboxylic acid cycle, suggesting that GLUD2 affects carbon flux during early brain development, possibly supporting lipid biosynthesis. PMID:27118840
Construction of 4D high-definition cortical surface atlases of infants: Methods and applications.
Li, Gang; Wang, Li; Shi, Feng; Gilmore, John H; Lin, Weili; Shen, Dinggang
2015-10-01
In neuroimaging, cortical surface atlases play a fundamental role for spatial normalization, analysis, visualization, and comparison of results across individuals and different studies. However, existing cortical surface atlases created for adults are not suitable for infant brains during the first two postnatal years, which is the most dynamic period of postnatal structural and functional development of the highly-folded cerebral cortex. Therefore, spatiotemporal cortical surface atlases for infant brains are highly desired yet still lacking for accurate mapping of early dynamic brain development. To bridge this significant gap, leveraging our infant-dedicated computational pipeline for cortical surface-based analysis and the unique longitudinal infant MRI dataset acquired in our research center, in this paper, we construct the first spatiotemporal (4D) high-definition cortical surface atlases for the dynamic developing infant cortical structures at seven time points, including 1, 3, 6, 9, 12, 18, and 24 months of age, based on 202 serial MRI scans from 35 healthy infants. For this purpose, we develop a novel method to ensure the longitudinal consistency and unbiasedness to any specific subject and age in our 4D infant cortical surface atlases. Specifically, we first compute the within-subject mean cortical folding by unbiased groupwise registration of longitudinal cortical surfaces of each infant. Then we establish longitudinally-consistent and unbiased inter-subject cortical correspondences by groupwise registration of the geometric features of within-subject mean cortical folding across all infants. Our 4D surface atlases capture both longitudinally-consistent dynamic mean shape changes and the individual variability of cortical folding during early brain development. Experimental results on two independent infant MRI datasets show that using our 4D infant cortical surface atlases as templates leads to significantly improved accuracy for spatial normalization of cortical surfaces across infant individuals, in comparison to the infant surface atlases constructed without longitudinal consistency and also the FreeSurfer adult surface atlas. Moreover, based on our 4D infant surface atlases, for the first time, we reveal the spatially-detailed, region-specific correlation patterns of the dynamic cortical developmental trajectories between different cortical regions during early brain development. Copyright © 2015 Elsevier B.V. All rights reserved.
Study of the development of fetal baboon brain using magnetic resonance imaging at 3 Tesla
Liu, Feng; Garland, Marianne; Duan, Yunsuo; Stark, Raymond I.; Xu, Dongrong; Dong, Zhengchao; Bansal, Ravi; Peterson, Bradley S.; Kangarlu, Alayar
2008-01-01
Direct observational data on the development of the brains of human and nonhuman primates is on remarkably scant, and most of our understanding of primate brain development is extrapolated from findings in rodent models. Magnetic resonance imaging (MRI) is a promising tool for the noninvasive, longitudinal study of the developing primate brain. We devised a protocol to scan pregnant baboons serially at 3 T for up to 3 h per session. Seven baboons were scanned 1–6 times, beginning as early as 56 days post-conceptional age, and as late as 185 days (term ~185 days). Successful scanning of the fetal baboon required careful animal preparation and anesthesia, in addition to optimization of the scanning protocol. We successfully acquired maps of relaxation times (T1 and T2) and high-resolution anatomical images of the brains of fetal baboons at multiple time points during the course of gestation. These images demonstrated the convergence of gray and white matter contrast near term, and furthermore demonstrated that the loss of contrast at that age is a consequence of the continuous change in relaxation times during fetal brain development. These data furthermore demonstrate that maps of relaxation times have clear advantages over the relaxation time weighted images for the tracking of the changes in brain structure during fetal development. This protocol for in utero MRI of fetal baboon brains will help to advance the use of nonhuman primate models to study fetal brain development longitudinally. PMID:18155925
Pénicaud, Sidonie; Klein, Denise; Zatorre, Robert J; Chen, Jen-Kai; Witcher, Pamela; Hyde, Krista; Mayberry, Rachel I
2013-02-01
Early language experience is essential for the development of a high level of linguistic proficiency in adulthood and in a recent functional Magnetic Resonance Imaging (fMRI) experiment, we showed that a delayed acquisition of a first language results in changes in the functional organization of the adult brain (Mayberry et al., 2011). The present study extends the question to explore if delayed acquisition of a first language also modulates the structural development of the brain. To this end, we carried out anatomical MRI in the same group of congenitally deaf individuals who varied in the age of acquisition of a first language, American Sign Language -ASL (Mayberry et al., 2011) and used a neuroanatomical technique, Voxel-Based Morphometry (VBM), to explore changes in gray and white matter concentrations across the brain related to the age of first language acquisition. The results show that delayed acquisition of a first language is associated with changes in tissue concentration in the occipital cortex close to the area that has been found to show functional recruitment during language processing in these deaf individuals with a late age of acquisition. These findings suggest that a lack of early language experience affects not only the functional but also the anatomical organization of the brain. Copyright © 2012 Elsevier Inc. All rights reserved.
Early development of synchrony in cortical activations in the human.
Koolen, N; Dereymaeker, A; Räsänen, O; Jansen, K; Vervisch, J; Matic, V; Naulaers, G; De Vos, M; Van Huffel, S; Vanhatalo, S
2016-05-13
Early intermittent cortical activity is thought to play a crucial role in the growth of neuronal network development, and large scale brain networks are known to provide the basis for higher brain functions. Yet, the early development of the large scale synchrony in cortical activations is unknown. Here, we tested the hypothesis that the early intermittent cortical activations seen in the human scalp EEG show a clear developmental course during the last trimester of pregnancy, the period of intensive growth of cortico-cortical connections. We recorded scalp EEG from altogether 22 premature infants at post-menstrual age between 30 and 44 weeks, and the early cortical synchrony was quantified using recently introduced activation synchrony index (ASI). The developmental correlations of ASI were computed for individual EEG signals as well as anatomically and mathematically defined spatial subgroups. We report two main findings. First, we observed a robust and statistically significant increase in ASI in all cortical areas. Second, there were significant spatial gradients in the synchrony in fronto-occipital and left-to-right directions. These findings provide evidence that early cortical activity is increasingly synchronized across the neocortex. The ASI-based metrics introduced in our work allow direct translational comparison to in vivo animal models, as well as hold promise for implementation as a functional developmental biomarker in future research on human neonates. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.
Bellés, María; Gilabert-Juan, Javier; Llorens, José Vicente; Bueno-Fernández, Clara; Ripoll-Martínez, Beatriz; Curto, Yasmina; Sebastiá-Ortega, Noelia; Sanjuan, Julio
2017-01-01
Abstract The exposure to aversive experiences during early life influences brain development and leads to altered behavior. Moreover, the combination of these experiences with subtle alterations in neurodevelopment may contribute to the emergence of psychiatric disorders, such as schizophrenia. Recent hypotheses suggest that imbalances between excitatory and inhibitory (E/I) neurotransmission, especially in the prefrontal cortex and the amygdala, may underlie their etiopathology. In order to understand better the neurobiological bases of these alterations, we studied the impact of altered neurodevelopment and chronic early-life stress on these two brain regions. Transgenic mice displaying fluorescent excitatory and inhibitory neurons, received a single injection of MK801 (NMDAR antagonist) or vehicle solution at postnatal day 7 and/or were socially isolated from the age of weaning until adulthood (3 months old). We found that anxiety-related behavior, brain volume, neuronal structure, and the expression of molecules related to plasticity and E/I neurotransmission in adult mice were importantly affected by early-life stress. Interestingly, many of these effects were potentiated when the stress paradigm was applied to mice perinatally injected with MK801 ("double-hit" model). These results clearly show the impact of early-life stress on the adult brain, especially on the structure and plasticity of inhibitory networks, and highlight the double-hit model as a valuable tool to study the contribution of early-life stress in the emergence of neurodevelopmental psychiatric disorders, such as schizophrenia. PMID:28466069
Fábián, Katalin; Gyulai, Márton; Furák, József; Várallyay, Péter; Jäckel, Márta; Bogos, Krisztina; Döme, Balázs; Pápay, Judit; Tímár, József; Szállási, Zoltán; Moldvay, Judit
2016-01-01
Brain metastasis of lung cancer adversely affects overall survival (OS) and quality of life, while peritumoral brain edema is responsible for life-threatening complications. We retrospectively analyzed the clinicopathological and cerebral radiological data of 575 consecutive lung cancer patients with brain metastases. In adenocarcinoma and squamous cell carcinoma, peritumoral brain edema was more pronounced than in small-cell lung cancer (p < 0.001 and p < 0.001, respectively). There was a positive correlation between the size of metastasis and the thickness of peritumoral brain edema (p < 0.001). It was thicker in supratentorial tumors (p = 0.019), in younger patients (≤50 years) (p = 0.042), and in females (p = 0.016). The time to development of brain metastasis was shorter in central than in peripheral lung cancer (5.3 vs. 9.0 months, p = 0.035). Early brain metastasis was characteristic for adenocarcinomas. A total of 135 patients had brain only metastases (N0 disease) characterized by peripheral lung cancer predominance (p < 0.001) and a longer time to development of brain metastasis (9.2 vs. 4.4 months, p < 0.001). OS was longer in the brain only subgroup than in patients with N1-3 diseases (p < 0.001). The clinicopathological characteristics of lung cancer are related to the development and radiographic features of brain metastases. Our results might be helpful in selecting patients who might benefit from prophylactic cranial irradiation. © 2016 S. Karger AG, Basel.
Ultrasound evaluation of cortical brain development in fetuses with intrauterine growth restriction.
Businelli, Caterina; de Wit, Charlotte; Visser, Gerard H A; Pistorius, Lourens R
2014-09-10
Abstract Objective: We evaluated the ultrasound appearance of brain volume and cortical development in fetuses with early growth restriction and placental insufficiency. Methods: We examined a cohort of 20 fetuses with severe intrauterine growth restriction (IUGR) and evidence of placental insufficiency by three-dimensional (3D) ultrasound between 24 and 34 weeks. We graded cortical development and measured the supratentorial intracranial volume. The cortical grading and volume were compared to data obtained from a reference population of 28 adequate for gestational age (AGA) fetuses. Results: Ultrasound examinations were performed in 20 fetuses with IUGR. The biometry and brain volume were significantly reduced in IUGR fetuses. There was evidence of accelerated cortical development in IUGR fetuses. Conclusion: This study confirms that the smaller brain volume in IUGR fetuses, with normal or accelerated cortical maturation as previously depicted with postnatal MRI examination, can be demonstrated by prenatal 3D ultrasound.
The role of inflammation in perinatal brain injury.
Hagberg, Henrik; Mallard, Carina; Ferriero, Donna M; Vannucci, Susan J; Levison, Steven W; Vexler, Zinaida S; Gressens, Pierre
2015-04-01
Inflammation is increasingly recognized as being a critical contributor to both normal development and injury outcome in the immature brain. The focus of this Review is to highlight important differences in innate and adaptive immunity in immature versus adult brain, which support the notion that the consequences of inflammation will be entirely different depending on context and stage of CNS development. Perinatal brain injury can result from neonatal encephalopathy and perinatal arterial ischaemic stroke, usually at term, but also in preterm infants. Inflammation occurs before, during and after brain injury at term, and modulates vulnerability to and development of brain injury. Preterm birth, on the other hand, is often a result of exposure to inflammation at a very early developmental phase, which affects the brain not only during fetal life, but also over a protracted period of postnatal life in a neonatal intensive care setting, influencing critical phases of myelination and cortical plasticity. Neuroinflammation during the perinatal period can increase the risk of neurological and neuropsychiatric disease throughout childhood and adulthood, and is, therefore, of concern to the broader group of physicians who care for these individuals.
The role of inflammation in perinatal brain injury
Hagberg, Henrik; Mallard, Carina; Ferriero, Donna M.; Vannucci, Susan J.; Levison, Steven W.; Vexler, Zinaida S.; Gressens, Pierre
2015-01-01
Inflammation is increasingly recognized as being a critical contributor to both normal development and injury outcome in the immature brain. The focus of this Review is to highlight important differences in innate and adaptive immunity in immature versus adult brain, which support the notion that the consequences of inflammation will be entirely different depending on context and stage of CNS development. Perinatal brain injury can result from neonatal encephalopathy and perinatal arterial ischaemic stroke, usually at term, but also in preterm infants. Inflammation occurs before, during and after brain injury at term, and modulates vulnerability to and development of brain injury. Preterm birth, on the other hand, is often a result of exposure to inflammation at a very early developmental phase, which affects the brain not only during fetal life, but also over a protracted period of postnatal life in a neonatal intensive care setting, influencing critical phases of myelination and cortical plasticity. Neuroinflammation during the perinatal period can increase the risk of neurological and neuropsychiatric disease throughout childhood and adulthood, and is, therefore, of concern to the broader group of physicians who care for these individuals. PMID:25686754
Intervention strategies for cesarean section-induced alterations in the microbiota-gut-brain axis.
Moya-Pérez, Angela; Luczynski, Pauline; Renes, Ingrid B; Wang, Shugui; Borre, Yuliya; Anthony Ryan, C; Knol, Jan; Stanton, Catherine; Dinan, Timothy G; Cryan, John F
2017-04-01
Microbial colonization of the gastrointestinal tract is an essential process that modulates host physiology and immunity. Recently, researchers have begun to understand how and when these microorganisms colonize the gut and the early-life factors that impact their natural ecological establishment. The vertical transmission of maternal microbes to the offspring is a critical factor for host immune and metabolic development. Increasing evidence also points to a role in the wiring of the gut-brain axis. This process may be altered by various factors such as mode of delivery, gestational age at birth, the use of antibiotics in early life, infant feeding, and hygiene practices. In fact, these early exposures that impact the intestinal microbiota have been associated with the development of diseases such as obesity, type 1 diabetes, asthma, allergies, and even neurodevelopmental disorders. The present review summarizes the impact of cesarean birth on the gut microbiome and the health status of the developing infant and discusses possible preventative and restorative strategies to compensate for early-life microbial perturbations. © The Author(s) 2017. Published by Oxford University Press on behalf of the International Life Sciences Institute.
... brain Early development of coronary artery disease (CAD) Endocarditis (infection in the heart) Heart failure Hoarseness Kidney ... include: Continued or repeated narrowing of the aorta Endocarditis High blood pressure
Hazards to Early Development: The Biological Embedding of Early Life Adversity.
Nelson, Charles A
2017-10-11
The number of children under 18 years of age has increased worldwide over the past decade. This growth spurt is due, in part, to remarkable progress in child survival. Alas, surviving early hazards, like prematurity or infectious disease, does not guarantee that children's development will not be compromised by other hazards as they grow older. Throughout the world, children continue to be confronted with a large number of biological and psychosocial challenges that greatly limit their developmental potential. The focus of this article is how such adverse experiences impact the developing brain. Copyright © 2017 Elsevier Inc. All rights reserved.
Brain sex differences and the organisation of juvenile social play behaviour.
Auger, A P; Olesen, K M
2009-06-01
Juvenile social play behaviour is one of the earliest forms of non-mother directed social behaviour in rodents. Juvenile social play behaviour is sexually dimorphic, with males exhibiting higher levels compared to females, making it a useful model to study both social development and sexual differentiation of the brain. As with most sexually dimorphic behaviour, juvenile play behaviour is organised by neonatal steroid hormone exposure. The developmental organisation of juvenile play behaviour also appears to be influenced by the early maternal environment. This review will focus briefly on why and how rats play, some brain regions controlling play behaviour, and how neurotransmitters and the social environment converge within the developing brain to influence sexual differentiation of juvenile play behaviour.
Bryck, Richard L.; Fisher, Philip A.
2012-01-01
Prior researchers have shown that the brain has a remarkable ability for adapting to environmental changes. The positive effects of such neural plasticity include enhanced functioning in specific cognitive domains and shifts in cortical representation following naturally occurring cases of sensory deprivation; however, maladaptive changes in brain function and development owing to early developmental adversity and stress have also been well documented. Researchers examining enriched rearing environments in animals have revealed the potential for inducing positive brain plasticity effects and have helped to popularize methods for training the brain to reverse early brain deficits or to boost normal cognitive functioning. In this paper, two classes of empirically based methods of brain training in children are reviewed and critiqued: laboratory-based, mental process training paradigms and ecological interventions based upon neurocognitive conceptual models. Given the susceptibility of executive function disruption, special attention is paid to training programs that emphasize executive function enhancement. In addition, a third approach to brain training, aimed at tapping into compensatory processes, is postulated. Study results showing the effectiveness of this strategy in the field of neurorehabilitation and in terms of naturally occurring compensatory processing in human aging lend credence to the potential of this approach. PMID:21787037
Bryck, Richard L; Fisher, Philip A
2012-01-01
Prior researchers have shown that the brain has a remarkable ability for adapting to environmental changes. The positive effects of such neural plasticity include enhanced functioning in specific cognitive domains and shifts in cortical representation following naturally occurring cases of sensory deprivation; however, maladaptive changes in brain function and development owing to early developmental adversity and stress have also been well documented. Researchers examining enriched rearing environments in animals have revealed the potential for inducing positive brain plasticity effects and have helped to popularize methods for training the brain to reverse early brain deficits or to boost normal cognitive functioning. In this article, two classes of empirically based methods of brain training in children are reviewed and critiqued: laboratory-based, mental process training paradigms and ecological interventions based upon neurocognitive conceptual models. Given the susceptibility of executive function disruption, special attention is paid to training programs that emphasize executive function enhancement. In addition, a third approach to brain training, aimed at tapping into compensatory processes, is postulated. Study results showing the effectiveness of this strategy in the field of neurorehabilitation and in terms of naturally occurring compensatory processing in human aging lend credence to the potential of this approach. (PsycINFO Database Record (c) 2012 APA, all rights reserved).
A Lifespan Approach to Neuroinflammatory and Cognitive Disorders: A Critical Role for Glia
Bilbo, Staci D.; Smith, Susan H.; Schwarz, Jaclyn M.
2011-01-01
Cognitive decline is a common problem of aging. Whereas multiple neural and glial mechanisms may account for these declines, microglial sensitization and/or dystrophy has emerged as a leading culprit in brain aging and dysfunction. However, glial activation is consistently observed in normal brain aging as well, independent of frank neuroinflammation or functional impairment. Such variability suggests the existence of additional vulnerability factors that can impact neuronal-glial interactions and thus overall brain and cognitive health. The goal of this review is to elucidate our working hypothesis that an individual‘s risk or resilience to neuroinflammatory disorders and poor cognitive aging may critically depend on their early life experience, which can change immune reactivity within the brain for the remainder of the lifespan. For instance, early-life infection in rats can profoundly disrupt memory function in young adulthood, as well as accelerate age-related cognitive decline, both of which are linked to enduring changes in glial function that occur in response to the initial infection. We discuss these findings within the context of the growing literature on the role of immune molecules and neuroimmune crosstalk in normal brain development. We highlight the intrinsic factors (e.g., chemokines, hormones) that regulate microglial development and their colonization of the embryonic and postnatal brain, and the capacity for disruption or “re-programming” of this crucial process by external events (e.g, stress, infection). An impact on glia, which in turn alters neural development, has the capacity to profoundly impact cognitive and mental health function at all stages of life. PMID:21822589
Bi-Parental Care Contributes to Sexually Dimorphic Neural Cell Genesis in the Adult Mammalian Brain
Mak, Gloria K.; Antle, Michael C.; Dyck, Richard H.; Weiss, Samuel
2013-01-01
Early life events can modulate brain development to produce persistent physiological and behavioural phenotypes that are transmissible across generations. However, whether neural precursor cells are altered by early life events, to produce persistent and transmissible behavioural changes, is unknown. Here, we show that bi-parental care, in early life, increases neural cell genesis in the adult rodent brain in a sexually dimorphic manner. Bi-parentally raised male mice display enhanced adult dentate gyrus neurogenesis, which improves hippocampal neurogenesis-dependent learning and memory. Female mice display enhanced adult white matter oligodendrocyte production, which increases proficiency in bilateral motor coordination and preference for social investigation. Surprisingly, single parent-raised male and female offspring, whose fathers and mothers received bi-parental care, respectively, display a similar enhancement in adult neural cell genesis and phenotypic behaviour. Therefore, neural plasticity and behavioural effects due to bi-parental care persist throughout life and are transmitted to the next generation. PMID:23650527
Ozernov-Palchik, Ola; Gaab, Nadine
2016-01-01
Developmental dyslexia is an unexplained inability to acquire accurate or fluent reading that affects approximately 5–17% of children. Dyslexia is associated with structural and functional alterations in various brain regions that support reading. Neuroimaging studies in infants and pre-reading children suggest that these alterations predate reading instruction and reading failure, supporting the hypothesis that variant function in dyslexia susceptibility genes lead to atypical neural migration and/or axonal growth during early, most likely in utero, brain development. Yet, dyslexia is typically not diagnosed until a child has failed to learn to read as expected (usually in second grade or later). There is emerging evidence that neuroimaging measures, when combined with key behavioral measures, can enhance the accuracy of identification of dyslexia risk in prereading children but its sensitivity, specificity, and cost-efficiency is still unclear. Early identification of dyslexia risk carries important implications for dyslexia remediation and the amelioration of the psychosocial consequences commonly associated with reading failure. PMID:26836227
How Early Events Affect Growing Brains. An Interview with Neuroscientist Pat Levitt
ERIC Educational Resources Information Center
National Scientific Council on the Developing Child, 2006
2006-01-01
Recent advances in neuroscience show clearly how experience can change brain neurochemicals, and how this in turn affects the way the brain functions. As a result, early negative events actually get built into the growing brain's neurochemistry, altering the brain's architecture. Research is continuing to investigate how children with genetic…
Poulsen, Ingrid; Kreiner, Svend; Engberg, Aase W
2018-02-13
The Early Functional Abilities scale assesses the restoration of brain function after brain injury, based on 4 dimensions. The primary objective of this study was to evaluate the validity, objectivity, reliability and measurement precision of the Early Functional Abilities scale by Rasch model item analysis. A secondary objective was to examine the relationship between the Early Functional Abilities scale and the Functional Independence Measurement™, in order to establish the criterion validity of the Early Functional Abilities scale and to compare the sensitivity of measurements using the 2 instruments. The Rasch analysis was based on the assessment of 408 adult patients at admission to sub-acute rehabilitation in Copenhagen, Denmark after traumatic brain injury. The Early Functional Abilities scale provides valid and objective measurement of vegetative (autonomic), facio-oral, sensorimotor and communicative/cognitive functions. Removal of one item from the sensorimotor scale confirmed unidimensionality for each of the 4 subscales, but not for the entire scale. The Early Functional Abilities subscales are sensitive to differences between patients in ranges in which the Functional Independence Measurement™ has a floor effect. The Early Functional Abilities scale assesses the early recovery of important aspects of brain function after traumatic brain injury, but is not unidimensional. We recommend removal of the "standing" item and calculation of summary subscales for the separate dimensions.
Boyd, Roslyn N; Jordan, Rachel; Pareezer, Laura; Moodie, Anne; Finn, Christine; Luther, Belinda; Arnfield, Evyn; Pym, Aaron; Craven, Alex; Beall, Paula; Weir, Kelly; Kentish, Megan; Wynter, Meredith; Ware, Robert; Fahey, Michael; Rawicki, Barry; McKinlay, Lynne; Guzzetta, Andrea
2013-06-11
Cerebral palsy (CP) results from a static brain lesion during pregnancy or early life and remains the most common cause of physical disability in children (1 in 500). While the brain lesion is static, the physical manifestations and medical issues may progress resulting in altered motor patterns. To date, there are no prospective longitudinal studies of CP that follow a birth cohort to track early gross and fine motor development and use Magnetic Resonance Imaging (MRI) to determine the anatomical pattern and likely timing of the brain lesion. Existing studies do not consider treatment costs and outcomes. This study aims to determine the pathway(s) to motor outcome from diagnosis at 18 months corrected age (c.a.) to outcome at 5 years in relation to the nature of the brain lesion (using structural MRI). This prospective cohort study aims to recruit a total of 240 children diagnosed with CP born in Victoria (birth years 2004 and 2005) and Queensland (birth years 2006-2009). Children can enter the study at any time between 18 months to 5 years of age and will be assessed at 18, 24, 30, 36, 48 and 60 months c.a. Outcomes include gross motor function (GMFM-66 & GMFM-88), Gross Motor Function Classification System (GMFCS); musculoskeletal development (hip displacement, spasticity, muscle contracture), upper limb function (Manual Ability Classification System), communication difficulties using Communication and Symbolic Behaviour Scales-Developmental Profile (CSBS-DP), participation using the Paediatric Evaluation of Disability Inventory (PEDI), parent reported quality of life and classification of medical and allied health resource use and determination of the aetiology of CP using clinical evaluation combined with MRI. The relationship between the pathways to motor outcome and the nature of the brain lesion will be analysed using multiple methods including non-linear modelling, multilevel mixed-effects models and generalised estimating equations. This protocol describes a large population-based study of early motor development and brain structure in a representative sample of preschool aged children with CP, using direct clinical assessment. The results of this study will be published in peer reviewed journals and presented at relevant international conferences. Australia and New Zealand Clinical Trials Register (ACTRN1261200169820).
2013-01-01
Background Cerebral palsy (CP) results from a static brain lesion during pregnancy or early life and remains the most common cause of physical disability in children (1 in 500). While the brain lesion is static, the physical manifestations and medical issues may progress resulting in altered motor patterns. To date, there are no prospective longitudinal studies of CP that follow a birth cohort to track early gross and fine motor development and use Magnetic Resonance Imaging (MRI) to determine the anatomical pattern and likely timing of the brain lesion. Existing studies do not consider treatment costs and outcomes. This study aims to determine the pathway(s) to motor outcome from diagnosis at 18 months corrected age (c.a.) to outcome at 5 years in relation to the nature of the brain lesion (using structural MRI). Methods This prospective cohort study aims to recruit a total of 240 children diagnosed with CP born in Victoria (birth years 2004 and 2005) and Queensland (birth years 2006–2009). Children can enter the study at any time between 18 months to 5 years of age and will be assessed at 18, 24, 30, 36, 48 and 60 months c.a. Outcomes include gross motor function (GMFM-66 & GMFM-88), Gross Motor Function Classification System (GMFCS); musculoskeletal development (hip displacement, spasticity, muscle contracture), upper limb function (Manual Ability Classification System), communication difficulties using Communication and Symbolic Behaviour Scales-Developmental Profile (CSBS-DP), participation using the Paediatric Evaluation of Disability Inventory (PEDI), parent reported quality of life and classification of medical and allied health resource use and determination of the aetiology of CP using clinical evaluation combined with MRI. The relationship between the pathways to motor outcome and the nature of the brain lesion will be analysed using multiple methods including non-linear modelling, multilevel mixed-effects models and generalised estimating equations. Discussion This protocol describes a large population-based study of early motor development and brain structure in a representative sample of preschool aged children with CP, using direct clinical assessment. The results of this study will be published in peer reviewed journals and presented at relevant international conferences. Trial registration Australia and New Zealand Clinical Trials Register (ACTRN1261200169820) PMID:23758951
Raschle, Nora Maria; Becker, Bryce Larkin Chessell; Smith, Sara; Fehlbaum, Lynn Valérie; Wang, Yingying; Gaab, Nadine
2017-01-01
Abstract Early language delay has often been associated with atypical language/literacy development. Neuroimaging studies further indicate functional disruptions during language and print processing in school-age children with a retrospective report of early language delay. Behavioral data of 114 5-year-olds with a retrospective report of early language delay in infancy (N = 34) and those without (N = 80) and with a familial risk for dyslexia and those without are presented. Behaviorally, children with a retrospective report of early language delay exhibited reduced performance in language/reading-related measures. A voxel-based morphometry analysis in a subset (N = 46) demonstrated an association between reduced gray matter volume and early language delay in left-hemispheric middle temporal, occipital, and frontal regions. Alterations in middle temporal cortex in children with a retrospective report of early language delay were observed regardless of familial risk for dyslexia. Additionally, while children with isolated familial risk for dyslexia showed gray matter reductions in temporoparietal and occipitotemporal regions, these effects were most profound in children with both risk factors. An interaction effect of early language delay and familial risk was revealed in temporoparietal, occipital, and frontal cortex. Our findings support a cumulative effect of early behavioral and genetic risk factors on brain development and may ultimately inform diagnosis/treatment. PMID:26585334
ERIC Educational Resources Information Center
Peters, Brenda; Forlin, Chris
2011-01-01
It is possible that many benefits may be found for all concerned in education and child development in understanding how knowledge of the brain and its development can inform early years practice. This article, written by Brenda Peters and Chris Forlin, both from the Hong Kong Institute of Education, reviews literature based on neuroscience to…
Lomanowska, A M; Boivin, M; Hertzman, C; Fleming, A S
2017-02-07
The developing brains of young children are highly sensitive to input from their social environment. Nurturing social experience during this time promotes the acquisition of social and cognitive skills and emotional competencies. However, many young children are confronted with obstacles to healthy development, including poverty, inappropriate care, and violence, and their enhanced sensitivity to the social environment means that they are highly susceptible to these adverse childhood experiences. One source of social adversity in early life can stem from parenting that is harsh, inconsistent, non-sensitive or hostile. Parenting is considered to be the cornerstone of early socio-emotional development and an adverse parenting style is associated with adjustment problems and a higher risk of developing mood and behavioral disorders. Importantly, there is a growing literature showing that an important predictor of parenting behavior is how parents, especially mothers, were parented themselves. In this review, we examine how adversity in early-life affects mothering behavior in later-life and how these effects may be perpetuated inter-generationally. Relying on studies in humans and animal models, we consider evidence for the intergenerational transmission of mothering styles. We then describe the psychological underpinnings of mothering, including responsiveness to young, executive function and affect, as well as the physiological mediators of mothering behavior, including hormones, brain regions and neurotransmitters, and we consider how development in these relevant domains may be affected by adversity experienced in early life. Finally, we explore how genes and early experience interact to predict mothering behavior, including the involvement of epigenetic mechanisms. Understanding how adverse parenting begets adverse parenting in the next generation is critical for designing interventions aimed at preventing this intergenerational cycle of early adversity. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.
George, Joanne M; Boyd, Roslyn N; Colditz, Paul B; Rose, Stephen E; Pannek, Kerstin; Fripp, Jurgen; Lingwood, Barbara E; Lai, Melissa M; Kong, Annice H T; Ware, Robert S; Coulthard, Alan; Finn, Christine M; Bandaranayake, Sasaka E
2015-09-16
More than 50 percent of all infants born very preterm will experience significant motor and cognitive impairment. Provision of early intervention is dependent upon accurate, early identification of infants at risk of adverse outcomes. Magnetic resonance imaging at term equivalent age combined with General Movements assessment at 12 weeks corrected age is currently the most accurate method for early prediction of cerebral palsy at 12 months corrected age. To date no studies have compared the use of earlier magnetic resonance imaging combined with neuromotor and neurobehavioural assessments (at 30 weeks postmenstrual age) to predict later motor and neurodevelopmental outcomes including cerebral palsy (at 12-24 months corrected age). This study aims to investigate i) the relationship between earlier brain imaging and neuromotor/neurobehavioural assessments at 30 and 40 weeks postmenstrual age, and ii) their ability to predict motor and neurodevelopmental outcomes at 3 and 12 months corrected age. This prospective cohort study will recruit 80 preterm infants born ≤ 30 week's gestation and a reference group of 20 healthy term born infants from the Royal Brisbane & Women's Hospital in Brisbane, Australia. Infants will undergo brain magnetic resonance imaging at approximately 30 and 40 weeks postmenstrual age to develop our understanding of very early brain structure at 30 weeks and maturation that occurs between 30 and 40 weeks postmenstrual age. A combination of neurological (Hammersmith Neonatal Neurologic Examination), neuromotor (General Movements, Test of Infant Motor Performance), neurobehavioural (NICU Network Neurobehavioural Scale, Premie-Neuro) and visual assessments will be performed at 30 and 40 weeks postmenstrual age to improve our understanding of the relationship between brain structure and function. These data will be compared to motor assessments at 12 weeks corrected age and motor and neurodevelopmental outcomes at 12 months corrected age (neurological assessment by paediatrician, Bayley scales of Infant and Toddler Development, Alberta Infant Motor Scale, Neurosensory Motor Developmental Assessment) to differentiate atypical development (including cerebral palsy and/or motor delay). Earlier identification of those very preterm infants at risk of adverse neurodevelopmental and motor outcomes provides an additional period for intervention to optimise outcomes. Australian New Zealand Clinical Trials Registry ACTRN12613000280707. Registered 8 March 2013.
Garner, Andrew S; Shonkoff, Jack P
2012-01-01
Advances in a wide range of biological, behavioral, and social sciences are expanding our understanding of how early environmental influences (the ecology) and genetic predispositions (the biologic program) affect learning capacities, adaptive behaviors, lifelong physical and mental health, and adult productivity. A supporting technical report from the American Academy of Pediatrics (AAP) presents an integrated ecobiodevelopmental framework to assist in translating these dramatic advances in developmental science into improved health across the life span. Pediatricians are now armed with new information about the adverse effects of toxic stress on brain development, as well as a deeper understanding of the early life origins of many adult diseases. As trusted authorities in child health and development, pediatric providers must now complement the early identification of developmental concerns with a greater focus on those interventions and community investments that reduce external threats to healthy brain growth. To this end, AAP endorses a developing leadership role for the entire pediatric community-one that mobilizes the scientific expertise of both basic and clinical researchers, the family-centered care of the pediatric medical home, and the public influence of AAP and its state chapters-to catalyze fundamental change in early childhood policy and services. AAP is committed to leveraging science to inform the development of innovative strategies to reduce the precipitants of toxic stress in young children and to mitigate their negative effects on the course of development and health across the life span.
Rocca, Christine
2015-09-01
A growing body of evidence suggests that musical activities can enhance the listening brain and develop higher cognitive functions, including linguistic abilities. The BabyBeats™ early intervention resource, a musical habilitation resource, was designed to improve early parent interaction, early listening behaviour, early communication skills, and social and emotional development, pre- and post-implantation. A feasibility study was conducted on families from the UK. There were two groups: seven babies <12 months old, with a varying degree of severe to profound hearing loss and eight infants who had been implanted with a cochlear implant and were now >12 months old. Audit data were collected based on a simple parental and professional feedback questionnaire, completed at the end of an 8-month trial. Parental feedback was positive and ideas from the resource were carried over into the family's everyday routines. Parents and professionals observed increased vocalisation, attention, and anticipation of the activities in their babies. Parents also reported increased confidence in singing, moving, and playing with their baby. These preliminary outcomes suggest that this type of intervention may lead to earlier development of communication and listening skills when used in combination with appropriate amplification. The next steps will be to include more infants, match the groups regarding age and developmental stage, to observe the infants for a longer period and to compare outcomes over time.
[Franz Joseph Gall and his "talking skulls" established the basis of modern brain sciences].
Wolfgang, Regal; Michael, Nanut
2008-01-01
The anatomist and brain scientist Franz Joseph Gall (1758-1828) developed the "phrenology" in the early 19(th) century. At this time, his new teachings were more seen as a temporary fashion than science and were discredited. No more than hundred years ago, it was realised that the phrenology established the basis of modern brain sciences. By all means Gall was the first one to combine defined regions of the cerebral cortex with distinct cognitive functions.
Simulation of blast-induced, early-time intracranial wave physics leading to traumatic brain injury.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Taylor, Paul Allen; Ford, Corey C.
U.S. soldiers are surviving blast and impacts due to effective body armor, trauma evacuation and care. Blast injuries are the leading cause of traumatic brain injury (TBI) in military personnel returning from combat. Understanding of Primary Blast Injury may be needed to develop better means of blast mitigation strategies. The objective of this paper is to investigate the effects of blast direction and strength on the resulting mechanical stress and wave energy distributions generated in the brain.
DHA Effects in Brain Development and Function
Lauritzen, Lotte; Brambilla, Paolo; Mazzocchi, Alessandra; Harsløf, Laurine B. S.; Ciappolino, Valentina; Agostoni, Carlo
2016-01-01
Docosahexaenoic acid (DHA) is a structural constituent of membranes specifically in the central nervous system. Its accumulation in the fetal brain takes place mainly during the last trimester of pregnancy and continues at very high rates up to the end of the second year of life. Since the endogenous formation of DHA seems to be relatively low, DHA intake may contribute to optimal conditions for brain development. We performed a narrative review on research on the associations between DHA levels and brain development and function throughout the lifespan. Data from cell and animal studies justify the indication of DHA in relation to brain function for neuronal cell growth and differentiation as well as in relation to neuronal signaling. Most data from human studies concern the contribution of DHA to optimal visual acuity development. Accumulating data indicate that DHA may have effects on the brain in infancy, and recent studies indicate that the effect of DHA may depend on gender and genotype of genes involved in the endogenous synthesis of DHA. While DHA levels may affect early development, potential effects are also increasingly recognized during childhood and adult life, suggesting a role of DHA in cognitive decline and in relation to major psychiatric disorders. PMID:26742060
DHA Effects in Brain Development and Function.
Lauritzen, Lotte; Brambilla, Paolo; Mazzocchi, Alessandra; Harsløf, Laurine B S; Ciappolino, Valentina; Agostoni, Carlo
2016-01-04
Docosahexaenoic acid (DHA) is a structural constituent of membranes specifically in the central nervous system. Its accumulation in the fetal brain takes place mainly during the last trimester of pregnancy and continues at very high rates up to the end of the second year of life. Since the endogenous formation of DHA seems to be relatively low, DHA intake may contribute to optimal conditions for brain development. We performed a narrative review on research on the associations between DHA levels and brain development and function throughout the lifespan. Data from cell and animal studies justify the indication of DHA in relation to brain function for neuronal cell growth and differentiation as well as in relation to neuronal signaling. Most data from human studies concern the contribution of DHA to optimal visual acuity development. Accumulating data indicate that DHA may have effects on the brain in infancy, and recent studies indicate that the effect of DHA may depend on gender and genotype of genes involved in the endogenous synthesis of DHA. While DHA levels may affect early development, potential effects are also increasingly recognized during childhood and adult life, suggesting a role of DHA in cognitive decline and in relation to major psychiatric disorders.
Total Environment Assessment of Stressors Associated with Cognitive Development - A Meta Analysis
Cognitive development (COGDEV) is marked by a number of critical periods during early childhood in which brain development is influenced by myriad chemical and non-chemical stressors from the built, natural, and social environments. Inherent factors and behaviors can also directl...
GENE EXPRESSION PROFILES IN THE DEVELOPING RAT CEREBELLUM AND HIPPOCAMPUS
Development of the nervous system is a complex program, involving coordinated growth of axons and their targets. In rodents, rapid brain growth occurs during early postnatal development. At this time, several fundamental processes, such as dendritic and axonal outgrowth and the e...
Impairment of Glymphatic Pathway Function Promotes Tau Pathology after Traumatic Brain Injury
Chen, Michael J.; Plog, Benjamin A.; Zeppenfeld, Douglas M.; Soltero, Melissa; Yang, Lijun; Singh, Itender; Deane, Rashid; Nedergaard, Maiken
2014-01-01
Traumatic brain injury (TBI) is an established risk factor for the early development of dementia, including Alzheimer's disease, and the post-traumatic brain frequently exhibits neurofibrillary tangles comprised of aggregates of the protein tau. We have recently defined a brain-wide network of paravascular channels, termed the “glymphatic” pathway, along which CSF moves into and through the brain parenchyma, facilitating the clearance of interstitial solutes, including amyloid-β, from the brain. Here we demonstrate in mice that extracellular tau is cleared from the brain along these paravascular pathways. After TBI, glymphatic pathway function was reduced by ∼60%, with this impairment persisting for at least 1 month post injury. Genetic knock-out of the gene encoding the astroglial water channel aquaporin-4, which is importantly involved in paravascular interstitial solute clearance, exacerbated glymphatic pathway dysfunction after TBI and promoted the development of neurofibrillary pathology and neurodegeneration in the post-traumatic brain. These findings suggest that chronic impairment of glymphatic pathway function after TBI may be a key factor that renders the post-traumatic brain vulnerable to tau aggregation and the onset of neurodegeneration. PMID:25471560
Reading Acquisition Enhances an Early Visual Process of Contour Integration
ERIC Educational Resources Information Center
Szwed, Marcin; Ventura, Paulo; Querido, Luis; Cohen, Laurent; Dehaene, Stanislas
2012-01-01
The acquisition of reading has an extensive impact on the developing brain and leads to enhanced abilities in phonological processing and visual letter perception. Could this expertise also extend to early visual abilities outside the reading domain? Here we studied the performance of illiterate, ex-illiterate and literate adults closely matched…
ERIC Educational Resources Information Center
Kumra, Sanjiv; Robinson, Paul; Tambyraja, Rabindra; Jensen, Daniel; Schimunek, Caroline; Houri, Alaa; Reis, Tiffany; Lim, Kelvin
2012-01-01
Objective: In early-onset schizophrenia (EOS), the earliest structural brain volumetric abnormalities appear in the parietal cortices. Early exposure to cannabis may represent an environmental risk factor for developing schizophrenia. This study characterized cerebral cortical gray matter structure in adolescents in regions of interest (ROIs) that…
Child Exposure to Violence as a Public Health Emergency
ERIC Educational Resources Information Center
Lieberman, Alicia F.; Soler, Esta
2013-01-01
Children's exposure to violence is a national crisis. The high prevalence of exposure to violence in infancy and early childhood has implications for lifelong health and development because early experiences are most influential in shaping the structure and functioning of the brain, the quality of attachments and other relationships, and the…
Early Childhood Household Smoke Exposure Predicts Less Task-Oriented Classroom Behavior at Age 10
ERIC Educational Resources Information Center
Pagani, Linda S.; Fitzpatrick, Caroline
2016-01-01
Secondhand tobacco smoke is considered a developmental neurotoxicant especially given underdeveloped vital systems in young children. An ecological test of its negative influence on brain development can be made by examining the prospective association between early childhood household smoke exposure and later classroom behavior. Using a…
Releasing the Voice of Early Education Directors: Degree Requirements
ERIC Educational Resources Information Center
Martin, Kristi Koenig
2011-01-01
The discovery of "windows of opportunity" regarding learning as the brain develops during the preschool years reinforces the important role early education teachers play in the lives of children. As a result, the credentials of those who work with young children have come under investigation as it relates to the provision of quality early…
ERIC Educational Resources Information Center
Bernier, Annie; Carlson, Stephanie M.; Whipple, Natasha
2010-01-01
In keeping with proposals emphasizing the role of early experience in infant brain development, this study investigated the prospective links between quality of parent-infant interactions and subsequent child executive functioning (EF), including working memory, impulse control, and set shifting. Maternal sensitivity, mind-mindedness and autonomy…
Role of erythropoietin in the brain
Noguchi, Constance Tom; Asavaritikrai, Pundit; Teng, Ruifeng; Jia, Yi
2007-01-01
Multi-tissue erythropoietin receptor (EPO-R) expression provides for erythropoietin (EPO) activity beyond its known regulation of red blood cell production. This review highlights the role of EPO and EPO-R in brain development and neuroprotection. EPO-R brain expression includes neural progenitor cells (NPC), neurons, glial cells and endothelial cells. EPO is produced in brain in a hypoxia sensitive manner, stimulates NPC proliferation and differentiation, and neuron survival, and contributes to ischemic preconditioning. Mice lacking EPO or EPO-R exhibit increased neural cell apoptosis during development before embryonic death due to severe anemia. EPO administration provides neural protection in animal models of brain ischemia and trauma, reducing the extent of injury and damage. EPO stimulation of endothelial cells contributes to neuroprotection and is of particular importance since only low levels of EPO appear to cross the blood-brain barrier when administered at high dose intravenously. The therapeutic potential of EPO for brain ischemia/trauma and neurodegenerative diseases has shown promise in early clinical trial and awaits further validation. PMID:17482474
Prenatal Brain MR Imaging: Reference Linear Biometric Centiles between 20 and 24 Gestational Weeks.
Conte, G; Milani, S; Palumbo, G; Talenti, G; Boito, S; Rustico, M; Triulzi, F; Righini, A; Izzo, G; Doneda, C; Zolin, A; Parazzini, C
2018-05-01
Evaluation of biometry is a fundamental step in prenatal brain MR imaging. While different studies have reported reference centiles for MR imaging biometric data of fetuses in the late second and third trimesters of gestation, no one has reported them in fetuses in the early second trimester. We report centiles of normal MR imaging linear biometric data of a large cohort of fetal brains within 24 weeks of gestation. From the data bases of 2 referral centers of fetal medicine, accounting for 3850 examinations, we retrospectively collected 169 prenatal brain MR imaging examinations of singleton pregnancies, between 20 and 24 weeks of gestational age, with normal brain anatomy at MR imaging and normal postnatal neurologic development. To trace the reference centiles, we used the CG-LMS method. Reference biometric centiles for the developing structures of the cerebrum, cerebellum, brain stem, and theca were obtained. The overall interassessor agreement was adequate for all measurements. Reference biometric centiles of the brain structures in fetuses between 20 and 24 weeks of gestational age may be a reliable tool in assessing fetal brain development. © 2018 by American Journal of Neuroradiology.
Horiquini-Barbosa, Everton; Gibb, Robbin; Kolb, Bryan; Bray, Douglas; Lachat, Joao-Jose
2017-02-15
Iron deficiency has a critical impact on maturational mechanisms of the brain and the damage related to neuroanatomical parameters is not satisfactorily reversed after iron replacement. However, emerging evidence suggest that enriched early experience may offer great therapeutic efficacy in cases of nutritional disorders postnatally, since the brain is remarkably responsive to its interaction with the environment. Given the fact that tactile stimulation (TS) treatment has been previously shown to be an effective therapeutic approach and with potential application to humans, here we ask whether exposure to TS treatment, from postnatal day (P) 1 to P32 for 3min/day, could also be employed to prevent neuroanatomical changes in the optic nerve of rats maintained on an iron-deficient diet during brain development. We found that iron deficiency changed astrocyte, oligodendrocyte, damaged fiber, and myelinated fiber density, however, TS reversed the iron-deficiency-induced alteration in oligodendrocyte, damaged fiber and myelinated fiber density, but failed to reverse astrocyte density. Our results suggest that early iron deficiency may act by disrupting the timing of key steps in visual system development thereby modifying the normal progression of optic nerve maturation. However, optic nerve development is sensitive to enriching experiences, and in the current study we show that this sensitivity can be used to prevent damage from postnatal iron deficiency during the critical period. Copyright © 2016 Elsevier B.V. All rights reserved.
Trainor, Laurel J
2012-02-01
Evidence is presented that predictive coding is fundamental to brain function and present in early infancy. Indeed, mismatch responses to unexpected auditory stimuli are among the earliest robust cortical event-related potential responses, and have been measured in young infants in response to many types of deviation, including in pitch, timing, and melodic pattern. Furthermore, mismatch responses change quickly with specific experience, suggesting that predictive coding reflects a powerful, early-developing learning mechanism. Copyright © 2011 Elsevier B.V. All rights reserved.
Hellström, Ann; Ley, David; Hansen-Pupp, Ingrid; Hallberg, Boubou; Ramenghi, Luca A.; Löfqvist, Chatarina; Smith, Lois E. H.; Hård, Anna-Lena
2018-01-01
The neonatal period of very preterm infants is often characterized by a difficult adjustment to extrauterine life, with an inadequate nutrient supply and insufficient levels of growth factors, resulting in poor growth and a high morbidity rate. Long-term multisystem complications include cognitive, behavioral, and motor dysfunction as a result of brain damage as well as visual and hearing deficits and metabolic disorders that persist into adulthood. Insulinlike growth factor 1 (IGF-1) is a major regulator of fetal growth and development of most organs especially the central nervous system including the retina. Glucose metabolism in the developing brain is controlled by IGF-1 which also stimulates differentiation and prevents apoptosis. Serum concentrations of IGF-1 decrease to very low levels after very preterm birth and remain low for most of the perinatal development. Strong correlations have been found between low neonatal serum concentrations of IGF-1 and poor brain and retinal growth as well as poor general growth with multiorgan morbidities, such as intraventricular hemorrhage, retinopathy of prematurity, bronchopulmonary dysplasia, and necrotizing enterocolitis. Experimental and clinical studies indicate that early supplementation with IGF-1 can improve growth in catabolic states and reduce brain injury after hypoxic/ischemic events. A multicenter phase II study is currently underway to determine whether intravenous replacement of human recombinant IGF-1 up to normal intrauterine serum concentrations can improve growth and development and reduce prematurity-associated morbidities. PMID:27603537
Brain network informed subject community detection in early-onset schizophrenia.
Yang, Zhi; Xu, Yong; Xu, Ting; Hoy, Colin W; Handwerker, Daniel A; Chen, Gang; Northoff, Georg; Zuo, Xi-Nian; Bandettini, Peter A
2014-07-03
Early-onset schizophrenia (EOS) offers a unique opportunity to study pathophysiological mechanisms and development of schizophrenia. Using 26 drug-naïve, first-episode EOS patients and 25 age- and gender-matched control subjects, we examined intrinsic connectivity network (ICN) deficits underlying EOS. Due to the emerging inconsistency between behavior-based psychiatric disease classification system and the underlying brain dysfunctions, we applied a fully data-driven approach to investigate whether the subjects can be grouped into highly homogeneous communities according to the characteristics of their ICNs. The resultant subject communities and the representative characteristics of ICNs were then associated with the clinical diagnosis and multivariate symptom patterns. A default mode ICN was statistically absent in EOS patients. Another frontotemporal ICN further distinguished EOS patients with predominantly negative symptoms. Connectivity patterns of this second network for the EOS patients with predominantly positive symptom were highly similar to typically developing controls. Our post-hoc functional connectivity modeling confirmed that connectivity strength in this frontotemporal circuit was significantly modulated by relative severity of positive and negative syndromes in EOS. This study presents a novel subtype discovery approach based on brain networks and proposes complex links between brain networks and symptom patterns in EOS.
Faleiros, Bruno E; Miranda, Aline S; Campos, Alline C; Gomides, Lindisley F; Kangussu, Lucas M; Guatimosim, Cristina; Camargos, Elizabeth R S; Menezes, Gustavo B; Rachid, Milene A; Teixeira, Antônio L
2014-08-26
The neurological involvement in acute liver failure (ALF) is characterized by arousal impairment with progression to coma. There is a growing body of evidence that neuroinflammatory mechanisms play a role in this process, including production of inflammatory cytokines and microglial activation. However, it is still uncertain whether brain-derived cytokines and glial cells are crucial to the pathophysiology of ALF at the early stage, before coma development. Here, we investigated the influence of cytokines and microglia in ALF-induced encephalopathy in mice as soon as neurological symptoms were identifiable. Behavior was assessed at 12, 24, 36 and 48 h post-injection of thioacetamide, a hepatotoxic drug, through locomotor activity by an open field test. Brain concentration of cytokines (TNF-α and IL-1β) and chemokines (CXCL1, CCL2, CCL3 and CCL5) were assessed by ELISA. Microglial activation in brain sections was investigated through immunohistochemistry, and cellular ultrastructural changes were observed by transmission electron microscopy. We found that ALF-induced animals presented a significant decrease in locomotor activity at 24 h, which was accompanied by an increase in IL-1β, CXCL1, CCL2, CCL3 and CCL5 in the brain. TNF-α level was significantly increased only at 36 h. Despite marked morphological changes in astrocytes and brain endothelial cells, no microglial activation was observed. These findings suggest an involvement of brain-derived chemokines and IL-1β in early pathophysiology of ALF by a mechanism independent of microglial activation. Copyright © 2014 Elsevier B.V. All rights reserved.
Im, K; Guimaraes, A; Kim, Y; Cottrill, E; Gagoski, B; Rollins, C; Ortinau, C; Yang, E; Grant, P E
2017-07-01
Aberrant gyral folding is a key feature in the diagnosis of many cerebral malformations. However, in fetal life, it is particularly challenging to confidently diagnose aberrant folding because of the rapid spatiotemporal changes of gyral development. Currently, there is no resource to measure how an individual fetal brain compares with normal spatiotemporal variations. In this study, we assessed the potential for automatic analysis of early sulcal patterns to detect individual fetal brains with cerebral abnormalities. Triplane MR images were aligned to create a motion-corrected volume for each individual fetal brain, and cortical plate surfaces were extracted. Sulcal basins were automatically identified on the cortical plate surface and compared with a combined set generated from 9 normal fetal brain templates. Sulcal pattern similarities to the templates were quantified by using multivariate geometric features and intersulcal relationships for 14 normal fetal brains and 5 fetal brains that were proved to be abnormal on postnatal MR imaging. Results were compared with the gyrification index. Significantly reduced sulcal pattern similarities to normal templates were found in all abnormal individual fetuses compared with normal fetuses (mean similarity [normal, abnormal], left: 0.818, 0.752; P < .001; right: 0.810, 0.753; P < .01). Altered location and depth patterns of sulcal basins were the primary distinguishing features. The gyrification index was not significantly different between the normal and abnormal groups. Automated analysis of interrelated patterning of early primary sulci could outperform the traditional gyrification index and has the potential to quantitatively detect individual fetuses with emerging abnormal sulcal patterns. © 2017 by American Journal of Neuroradiology.
Gaining Insight of Fetal Brain Development with Diffusion MRI and Histology
Huang, Hao; Vasung, Lana
2013-01-01
Human brain is extraordinarily complex and yet its origin is a simple tubular structure. Its development during the fetal period is characterized by a series of accurately organized events which underlie the mechanisms of dramatic structural changes during fetal development. Revealing detailed anatomy at different stages of human fetal brain development provides insight on understanding not only this highly ordered process, but also the neurobiological foundations of cognitive brain disorders such as mental retardation, autism, schizophrenia, bipolar and language impairment. Diffusion tensor imaging (DTI) and histology are complementary tools which are capable of delineating the fetal brain structures at both macroscopic and microscopic level. In this review, the structural development of the fetal brains has been characterized with DTI and histology. Major components of the fetal brain, including cortical plate, fetal white matter and cerebral wall layer between the ventricle and subplate, have been delineated with DTI and histology. Anisotropic metrics derived from DTI were used to quantify the microstructural changes during the dynamic process of human fetal cortical development and prenatal development of other animal models. Fetal white matter pathways have been traced with DTI-based tractography to reveal growth patterns of individual white matter tracts and corticocortical connectivity. These detailed anatomical accounts of the structural changes during fetal period may provide the clues of detecting developmental and cognitive brain disorders at their early stages. The anatomical information from DTI and histology may also provide reference standards for diagnostic radiology of premature newborns. PMID:23796901
Dynamic variation in forebrain estradiol levels during song learning
Chao, Andrew; Paon, Ashley; Remage-Healey, Luke
2014-01-01
Estrogens shape brain circuits during development, and the capacity to synthesize estrogens locally has consequences for both sexual differentiation and the acute modulation of circuits during early learning. A recently-optimized method to detect and quantify fluctuations in brain estrogens in vivo provides a direct means to explore how brain estrogen production contributes to both differentiation and neuromodulation during development. Here, we use this method to test the hypothesis that neuroestrogens are sexually-differentiated as well as dynamically responsive to song tutoring (via passive video/audio playback) during the period of song learning in juvenile zebra finches. Our results show that baseline neuroestradiol levels in the caudal forebrain do not differ between males and females during an early critical masculinization window. Instead, we observe a prominent difference between males and females in baseline neuroestradiol that emerges during the subadult stage as animals approach sexual maturity. Second, we observe that fluctuating neuroestradiol levels during periods of passive song tutoring exhibit a markedly different profile in juveniles as compared to adults. Specifically, neuroestrogens in the caudal forebrain are elevated following (rather than during) tutor song exposure in both juvenile males and females, suggesting an important role for the early consolidation of tutor song memories. These results further reveal a circadian influence on the fluctuations in local neuroestrogens during sensory/cognitive tasks. Taken together, these findings uncover several unexpected features of brain estrogen synthesis in juvenile animals that may have implications for secondary masculinization as well as the consolidation of recent sensory experiences. PMID:25205304
Human Fetal Brain Connectome: Structural Network Development from Middle Fetal Stage to Birth
Song, Limei; Mishra, Virendra; Ouyang, Minhui; Peng, Qinmu; Slinger, Michelle; Liu, Shuwei; Huang, Hao
2017-01-01
Complicated molecular and cellular processes take place in a spatiotemporally heterogeneous and precisely regulated pattern in the human fetal brain, yielding not only dramatic morphological and microstructural changes, but also macroscale connectomic transitions. As the underlying substrate of the fetal brain structural network, both dynamic neuronal migration pathways and rapid developing fetal white matter (WM) fibers could fundamentally reshape early fetal brain connectome. Quantifying structural connectome development can not only shed light on the brain reconfiguration in this critical yet rarely studied developmental period, but also reveal alterations of the connectome under neuropathological conditions. However, transition of the structural connectome from the mid-fetal stage to birth is not yet known. The contribution of different types of neural fibers to the structural network in the mid-fetal brain is not known, either. In this study, diffusion tensor magnetic resonance imaging (DT-MRI or DTI) of 10 fetal brain specimens at the age of 20 postmenstrual weeks (PMW), 12 in vivo brains at 35 PMW, and 12 in vivo brains at term (40 PMW) were acquired. The structural connectome of each brain was established with evenly parcellated cortical regions as network nodes and traced fiber pathways based on DTI tractography as network edges. Two groups of fibers were categorized based on the fiber terminal locations in the cerebral wall in the 20 PMW fetal brains. We found that fetal brain networks become stronger and more efficient during 20–40 PMW. Furthermore, network strength and global efficiency increase more rapidly during 20–35 PMW than during 35–40 PMW. Visualization of the whole brain fiber distribution by the lengths suggested that the network reconfiguration in this developmental period could be associated with a significant increase of major long association WM fibers. In addition, non-WM neural fibers could be a major contributor to the structural network configuration at 20 PMW and small-world network organization could exist as early as 20 PMW. These findings offer a preliminary record of the fetal brain structural connectome maturation from the middle fetal stage to birth and reveal the critical role of non-WM neural fibers in structural network configuration in the middle fetal stage. PMID:29081731
Epigenetic Influences on Brain Development and Plasticity
Fagiolini, Michela; Jensen, Catherine L.; Champagne, Frances A.
2009-01-01
A fine interplay exists between sensory experience and innate genetic programs leading to the sculpting of neuronal circuits during early brain development. Recent evidence suggests that the dynamic regulation of gene expression through epigenetic mechanisms is at the interface between environmental stimuli and long-lasting molecular, cellular and complex behavioral phenotypes acquired during periods of developmental plasticity. Understanding these mechanisms may give insight into the formation of critical periods and provide new strategies for increasing plasticity and adaptive change in adulthood. PMID:19545993
Neurodevelopmental origins of lifespan changes in brain and cognition
Walhovd, Kristine B.; Krogsrud, Stine K.; Bartsch, Hauke; Bjørnerud, Atle; Due-Tønnessen, Paulina; Grydeland, Håkon; Hagler, Donald J.; Håberg, Asta K.; Kremen, William S.; Ferschmann, Lia; Nyberg, Lars; Panizzon, Matthew S.; Rohani, Darius A.; Skranes, Jon; Storsve, Andreas B.; Sølsnes, Anne Elisabeth; Tamnes, Christian K.; Thompson, Wesley K.; Reuter, Chase; Dale, Anders M.; Fjell, Anders M.
2016-01-01
Neurodevelopmental origins of functional variation in older age are increasingly being acknowledged, but identification of how early factors impact human brain and cognition throughout life has remained challenging. Much focus has been on age-specific mechanisms affecting neural foundations of cognition and their change. In contrast to this approach, we tested whether cerebral correlates of general cognitive ability (GCA) in development could be extended to the rest of the lifespan, and whether early factors traceable to prenatal stages, such as birth weight and parental education, may exert continuous influences. We measured the area of the cerebral cortex in a longitudinal sample of 974 individuals aged 4–88 y (1,633 observations). An extensive cortical region was identified wherein area related positively to GCA in development. By tracking area of the cortical region identified in the child sample throughout the lifespan, we showed that the cortical change trajectories of higher and lower GCA groups were parallel through life, suggesting continued influences of early life factors. Birth weight and parental education obtained from the Norwegian Mother–Child Cohort study were identified as such early factors of possible life-long influence. Support for a genetic component was obtained in a separate twin sample (Vietnam Era Twin Study of Aging), but birth weight in the child sample had an effect on cortical area also when controlling for possible genetic differences in terms of parental height. Our results provide novel evidence for stability in brain–cognition relationships throughout life, and indicate that early life factors impact brain and cognition for the entire life course. PMID:27432992
An agenda for 21st century neurodevelopmental medicine: lessons from autism.
Klin, A; Jones, W
2018-03-01
The future of neurodevelopmental medicine has the potential of situating child neurology at the forefront of a broad-based public health effort to optimize neurodevelopmental outcomes of children born with high-prevalence and diverse genetic, pre- and peri-natal, and environmental burdens compromising early brain development and leading to lifetime disabilities. Building on advancements in developmental social neuroscience and in implementation science, this shift is already occurring in the case of emblematic neurodevelopmental disorders such as autism. Capitalizing on early neuroplasticity and on quantification of trajectories of social-communicative development, new technologies are emerging for high-throughput and cost-effective diagnosis and for community-viable delivery of powerful treatments, in seamless integration across previously fragmented systems of healthcare delivery. These solutions could be deployed in the case of other groups of children at greater risk for autism and communication delays, such as those born extremely premature or with congenital heart disease. The galvanizing concept in this aspirational future is a public health focus on promoting optimal conditions for early brain development, not unlike current campaigns promoting pre-natal care, nutrition or vaccination.
Sinha, Rohit Anthony; Pathak, Amrita; Mohan, Vishwa; Babu, Satish; Pal, Amit; Khare, Drirh; Godbole, Madan M
2010-07-02
Hypothyroidism during early mammalian brain development is associated with decreased expression of various mitochondrial encoded genes along with evidence for mitochondrial dysfunction. However, in-spite of the similarities between neurological disorders caused by perinatal hypothyroidism and those caused by various genetic mitochondrial defects we still do not know as to how thyroid hormone (TH) regulates mitochondrial transcription during development and whether this regulation by TH is nuclear mediated or through mitochondrial TH receptors? We here in rat cerebellum show that hypothyroidism causes reduction in expression of nuclear encoded genes controlling mitochondrial biogenesis like PGC-1alpha, NRF-1alpha and Tfam. Also, we for the first time demonstrate a mitochondrial localization of thyroid hormone receptor (mTR) isoform in developing brain capable of binding a TH response element (DR2) present in D-loop region of mitochondrial DNA. These results thus indicate an integrated nuclear-mitochondrial cross talk in regulation of mitochondrial transcription by TH during brain development. Copyright 2010 Elsevier Inc. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Sinha, Rohit Anthony; Pathak, Amrita; Mohan, Vishwa
Hypothyroidism during early mammalian brain development is associated with decreased expression of various mitochondrial encoded genes along with evidence for mitochondrial dysfunction. However, in-spite of the similarities between neurological disorders caused by perinatal hypothyroidism and those caused by various genetic mitochondrial defects we still do not know as to how thyroid hormone (TH) regulates mitochondrial transcription during development and whether this regulation by TH is nuclear mediated or through mitochondrial TH receptors? We here in rat cerebellum show that hypothyroidism causes reduction in expression of nuclear encoded genes controlling mitochondrial biogenesis like PGC-1{alpha}, NRF-1{alpha} and Tfam. Also, we for themore » first time demonstrate a mitochondrial localization of thyroid hormone receptor (mTR) isoform in developing brain capable of binding a TH response element (DR2) present in D-loop region of mitochondrial DNA. These results thus indicate an integrated nuclear-mitochondrial cross talk in regulation of mitochondrial transcription by TH during brain development.« less
Three patients with hemophagocytic syndrome who developed acute organic brain syndrome.
Shinno, Hideto; Hikasa, Satoshi; Matsuoka, Tatsuo; Fujita, Hidekazu; Yamamoto, Osamu; Takebayashi, Minoru; Uchida, Youzou; Nishiura, Tetsuo; Horiguchi, Jun
2006-01-01
We describe three patients with hemophagocytic syndrome (HPS) who developed acute organic brain syndrome. All three presented with high-grade fever and twilight state, and were admitted to our hospital. After admission, delirium developed in all three. As delirium improved, various other psychiatric symptoms, including hallucinations, agitation, hypoactivity, affective lability and insomnia, were noted. When treated with steroid hormones, immunoglobulin and neuroleptics, all patients demonstrated improvement in their psychiatric symptoms, as well as in their general condition and laboratory findings. Ultimately, they all recovered and were discharged. It needs to be noted that organic brain syndrome might be observed at the onset of HPS. Consequently, early diagnosis and treatment for psychiatric symptoms, as well as for HPS, are crucial.
[Developmental neurotoxicity of industrial chemicals].
Labie, Dominique
2007-10-01
"A Silent Pandemic : Industrial Chemicals Are Impairing the Brain Development of Children Worldwide" Fetal and early childhood exposures to industrial chemicals in the environment can damage the developing brain and can lead to neurodevelopmental disorders (NDDs)--autism, attention deficit disorder (ADHD), and mental retardation. In a new review study, published in The Lancet, Philip Grandjean and Philip Landrigan from the Harvard School of Public Health systematically examined publicly available data on chemical toxicity in order to identify the industrial chemicals that are the most likely to damage the developing brain. The researchers found that 202 industrial chemicals have the capacity to damage the human brain, and they conclude that chemical pollution may have harmed the brains of millions of children worldwide. The authors conclude further that the toxic effects of industrial chemicals on children have generally been overlooked. In North Amercia, the commission for environmental cooperation, and in European Union the DEVNERTOX projects had reached to the same conclusions. We analyse this review and discuss these rather pessimistic conclusions.
Wu, Yibo; Lv, Zhuo; Yang, Yang; Dong, Guoying; Yu, Yang; Cui, Yiqiang; Tong, Man; Wang, Liu; Zhou, Zuomin; Zhu, Hui; Zhou, Qi; Sha, Jiahao
2014-05-01
Blastomere biopsy is used in preimplantation genetic diagnosis; however, the long-term implications on the offspring are poorly characterized. We previously reported a high risk of memory defects in adult biopsied mice. Here, we assessed nervous function of aged biopsied mice and further investigated the mechanism of neural impairment after biopsy. We found that aged biopsied mice had poorer spatial learning ability, increased neuron degeneration, and altered expression of proteins involved in neural degeneration or dysfunction in the brain compared to aged control mice. Furthermore, the MeDIP assay indicated a genome-wide low methylation in the brains of adult biopsied mice when compared to the controls, and most of the genes containing differentially methylated loci in promoter regions were associated with neural disorders. When we further compared the genomic DNA methylation profiles of 7.5-days postconception (dpc) embryos between the biopsy and control group, we found the whole genome low methylation in the biopsied group, suggesting that blastomere biopsy was an obstacle to de novo methylation during early embryo development. Further analysis on mRNA profiles of 4.5-dpc embryos indicated that reduced expression of de novo methylation genes in biopsied embryos may impact de novo methylation. In conclusion, we demonstrate an abnormal neural development and function in mice generated after blastomere biopsy. The impaired epigenetic reprogramming during early embryo development may be the latent mechanism contributing to the impairment of the nervous system in the biopsied mice, which results in a hypomethylation status in their brains.
Effects of prenatal maternal stress on serotonin and fetal development.
St-Pierre, Joey; Laurent, Laetitia; King, Suzanne; Vaillancourt, Cathy
2016-12-01
Fetuses are exposed to many environmental perturbations that can influence their development. These factors can be easily identifiable such as drugs, chronic diseases or prenatal maternal stress. Recently, it has been demonstrated that the serotonin synthetized by the placenta was crucial for fetal brain development. Moreover, many studies show the involvement of serotonin system alteration in psychiatric disease during childhood and adulthood. This review summarizes existing studies showing that prenatal maternal stress, which induces alteration of serotonin systems (placenta and fetal brain) during a critical window of early development, could lead to alteration of fetal development and increase risks of psychiatric diseases later in life. This phenomenon, termed fetal programming, could be moderated by the sex of the fetus. This review highlights the need to better understand the modification of the maternal, placental and fetal serotonin systems induced by prenatal maternal stress in order to find early biomarkers of psychiatric disorders. Copyright © 2015 Elsevier Ltd. All rights reserved.
Linke, Annika C; Wild, Conor; Zubiaurre-Elorza, Leire; Herzmann, Charlotte; Duffy, Hester; Han, Victor K; Lee, David S C; Cusack, Rhodri
2018-01-01
Functional connectivity magnetic resonance imaging (fcMRI) of neonates with perinatal brain injury could improve prediction of motor impairment before symptoms manifest, and establish how early brain organization relates to subsequent development. This cohort study is the first to describe and quantitatively assess functional brain networks and their relation to later motor skills in neonates with a diverse range of perinatal brain injuries. Infants ( n = 65, included in final analyses: n = 53) were recruited from the neonatal intensive care unit (NICU) and were stratified based on their age at birth (premature vs. term), and on whether neuropathology was diagnosed from structural MRI. Functional brain networks and a measure of disruption to functional connectivity were obtained from 14 min of fcMRI acquired during natural sleep at term-equivalent age. Disruption to connectivity of the somatomotor and frontoparietal executive networks predicted motor impairment at 4 and 8 months. This disruption in functional connectivity was not found to be driven by differences between clinical groups, or by any of the specific measures we captured to describe the clinical course. fcMRI was predictive over and above other clinical measures available at discharge from the NICU, including structural MRI. Motor learning was affected by disruption to somatomotor networks, but also frontoparietal executive networks, which supports the functional importance of these networks in early development. Disruption to these two networks might be best addressed by distinct intervention strategies.
Neural signatures of conscious and unconscious emotional face processing in human infants.
Jessen, Sarah; Grossmann, Tobias
2015-03-01
Human adults can process emotional information both with and without conscious awareness, and it has been suggested that the two processes rely on partly distinct brain mechanisms. However, the developmental origins of these brain processes are unknown. In the present event-related brain potential (ERP) study, we examined the brain responses of 7-month-old infants in response to subliminally (50 and 100 msec) and supraliminally (500 msec) presented happy and fearful facial expressions. Our results revealed that infants' brain responses (Pb and Nc) over central electrodes distinguished between emotions irrespective of stimulus duration, whereas the discrimination between emotions at occipital electrodes (N290 and P400) only occurred when faces were presented supraliminally (above threshold). This suggests that early in development the human brain not only discriminates between happy and fearful facial expressions irrespective of conscious perception, but also that, similar to adults, supraliminal and subliminal emotion processing relies on distinct neural processes. Our data further suggest that the processing of emotional facial expressions differs across infants depending on their behaviorally shown perceptual sensitivity. The current ERP findings suggest that distinct brain processes underpinning conscious and unconscious emotion perception emerge early in ontogeny and can therefore be seen as a key feature of human social functioning. Copyright © 2014 Elsevier Ltd. All rights reserved.
Wolf, R C; Sambataro, F; Vasic, N; Depping, M S; Thomann, P A; Landwehrmeyer, G B; Süssmuth, S D; Orth, M
2014-11-01
Functional magnetic resonance imaging (fMRI) of multiple neural networks during the brain's 'resting state' could facilitate biomarker development in patients with Huntington's disease (HD) and may provide new insights into the relationship between neural dysfunction and clinical symptoms. To date, however, very few studies have examined the functional integrity of multiple resting state networks (RSNs) in manifest HD, and even less is known about whether concomitant brain atrophy affects neural activity in patients. Using MRI, we investigated brain structure and RSN function in patients with early HD (n = 20) and healthy controls (n = 20). For resting-state fMRI data a group-independent component analysis identified spatiotemporally distinct patterns of motor and prefrontal RSNs of interest. We used voxel-based morphometry to assess regional brain atrophy, and 'biological parametric mapping' analyses to investigate the impact of atrophy on neural activity. Compared with controls, patients showed connectivity changes within distinct neural systems including lateral prefrontal, supplementary motor, thalamic, cingulate, temporal and parietal regions. In patients, supplementary motor area and cingulate cortex connectivity indices were associated with measures of motor function, whereas lateral prefrontal connectivity was associated with cognition. This study provides evidence for aberrant connectivity of RSNs associated with motor function and cognition in early manifest HD when controlling for brain atrophy. This suggests clinically relevant changes of RSN activity in the presence of HD-associated cortical and subcortical structural abnormalities.
Regulation of Adult Neurogenesis and Plasticity by (Early) Stress, Glucocorticoids, and Inflammation
Lucassen, Paul J.; Oomen, Charlotte A.; Naninck, Eva F.G.; Fitzsimons, Carlos P.; van Dam, Anne-Marie; Czeh, Boldizsár; Korosi, Aniko
2015-01-01
Exposure to stress is one of the best-known negative regulators of adult neurogenesis (AN). We discuss changes in neurogenesis in relation to exposure to stress, glucocorticoid hormones, and inflammation, with a particular focus on early development and on lasting effects of stress. Although the effects of acute and mild stress on AN are generally brief and can be quickly overcome, chronic exposure or more severe forms of stress can induce longer lasting reductions in neurogenesis that can, however, in part, be overcome by subsequent exposure to exercise, drugs targeting the stress system, and some antidepressants. Exposure to stress, particularly during the sensitive period of early life, may (re)program brain plasticity, in particular, in the hippocampus. This may increase the risk to develop cognitive or anxiety symptoms, common to brain diseases like dementia and depression in which plasticity changes occur, and a normalization of neurogenesis may be required for a successful treatment response and recovery. PMID:26330520
Cookey, Jacob; Bernier, Denise; Tibbo, Philip G
2014-07-01
The impact of cannabis use on the brain tissue is still unclear, both in the healthy developing brain and in people with schizophrenia. The focus of this review is on white matter, the primary connective infrastructure of the brain. We systematically reviewed diffusion tensor imaging (DTI) studies of early phase schizophrenia (illness effect), of cannabis use in otherwise healthy brains (drug effect), and of early phase schizophrenia with cannabis use (combined effects). Studies had to include a healthy, non-cannabis using, control group as well as report on fractional anisotropy as it is the most commonly used DTI index. We excluded cohorts with heavy alcohol or illicit drug use and studies with a sample size of less than 20 in the clinical group. We retained 17 studies of early phase schizophrenia, which together indicate deficits in white matter integrity observed in all fiber tract families, but most frequently in association, callosal and projection fibers. In otherwise healthy cannabis users (2 studies), deficits in white matter tracts were reported mainly in callosal fibers, but also in projection and limbic fibers. In cannabis users with early phase schizophrenia (1 study), deficits in white matter integrity were also observed in all fiber tract families, except for limbic fibers. The current literature points to several families of white matter tracts being differentially affected in early phase schizophrenia. Further work is required to reveal the impact of cannabis use in otherwise healthy people as well as those with schizophrenia. Paucity of available studies as well as restricting analysis to FA values represent the main limitations of this review. Copyright © 2014 Elsevier B.V. All rights reserved.
Cadenas-Sánchez, Cristina; Mora-González, José; Migueles, Jairo H; Martín-Matillas, Miguel; Gómez-Vida, José; Escolano-Margarit, María Victoria; Maldonado, José; Enriquez, Gala María; Pastor-Villaescusa, Belén; de Teresa, Carlos; Navarrete, Socorro; Lozano, Rosa María; de Dios Beas-Jiménez, Juan; Estévez-López, Fernando; Mena-Molina, Alejandra; Heras, María José; Chillón, Palma; Campoy, Cristina; Muñoz-Hernández, Victoria; Martínez-Ávila, Wendy Daniela; Merchan, María Elisa; Perales, José C; Gil, Ángel; Verdejo-García, Antonio; Aguilera, Concepción M; Ruiz, Jonatan R; Labayen, Idoia; Catena, Andrés; Ortega, Francisco B
2016-03-01
The new and recent advances in neuroelectric and neuroimaging technologies provide a new era for further exploring and understanding how brain and cognition function can be stimulated by environmental factors, such as exercise, and particularly to study whether physical exercise influences brain development in early ages. The present study, namely the ActiveBrains project, aims to examine the effects of a physical exercise programme on brain and cognition, as well as on selected physical and mental health outcomes in overweight/obese children. A total of 100 participants aged 8 to 11 years are randomized into an exercise group (N=50) or a control group (N=50). The intervention lasts 20-weeks, with 3-5 sessions per week of 90 min each, and is mainly focused on high-intensity aerobic exercise yet also includes muscle-strengthening exercises. The extent to what the intervention effect remains 8-months after the exercise programme finishes is also studied in a subsample. Brain structure and function and cognitive performance are assessed using structural and functional magnetic resonance imaging and electroencephalographic recordings. Secondary outcomes include physical health outcomes (e.g. physical fitness, body fatness, bone mass and lipid-metabolic factors) and mental health outcomes (e.g. chronic stress indicators and overall behavioural and personality measurements such as anxiety or depression). This project will substantially contribute to the existing knowledge and will have an impact on societies, since early stimulation of brain development might have long lasting consequences on cognitive performance, academic achievement and in the prevention of behavioural problems and the promotion of psychological adjustment and mental health. Clinical trials. Gov identifier: NCT02295072. Copyright © 2016 Elsevier Inc. All rights reserved.
Similarities and differences between the Wnt and reelin pathways in the forming brain.
Reiner, Orly; Sapir, Tamar
2005-01-01
One of the key features in development is the reutilization of successful signaling pathways. Here, we emphasize the involvement of the Wnt pathway, one of the five kinds of signal transduction pathway predominating early embryonic development of all animals, in regulating the formation of brain structure. We discuss the interrelationships between the Wnt and reelin pathways in the regulation of cortical layering. We summarize data emphasizing key molecules, which, when mutated, result in abnormal brain development. This integrated view, which is based on conservation of pathways, reveals the relative position of participants in the pathway, points to control mechanisms, and allows raising testable working hypotheses. Nevertheless, although signaling pathways are highly conserved from flies to humans, the overall morphology is not. We propose that future studies directed at understanding of diversification will provide fruitful insights on mammalian brain formation.
Bell, Margaret R.; Hart, Bethany G.; Gore, Andrea C.
2015-01-01
Exposures to polychlorinated biphenyls (PCBs) during early development have long-lasting, sexually dimorphic consequences on adult brain and behavior. However, few studies have investigated their effects during juvenile development, a time when increases in pubertal hormones influence brain maturation. Here, male and female Sprague Dawley rats were exposed to PCBs (Aroclor 1221, 1 mg/kg/day) or vehicle prenatally, during juvenile development, or both, and their effects on serum hormone concentrations, gene expression, and DNA methylation were assessed in adulthood. Gene expression in male but not female brains was affected by 2-hits of PCBs, a result that paralleled behavioral effects of PCBs. Furthermore, the second hit often changed the effects of a first hit in complex ways. Thus, PCB exposures during critical fetal and juvenile developmental periods result in unique neuromolecular phenotypes, with males most vulnerable to the treatments. PMID:26620572
Neurosteroid production in the songbird brain: a re-evaluation of core principles
London, Sarah E.; Remage-Healey, Luke; Schlinger, Barney A.
2009-01-01
Concepts of brain-steroid signaling have traditionally placed emphasis on the gonads and adrenals as the source of steroids, the strict dichotomy of early developmental (“organizational”) and mature (“activational”) effects, and a relatively slow mechanism of signaling through intranuclear receptors. Continuing research shows that these concepts are not inaccurate, but they are certainly incomplete. In this review, we focus on the song control circuit of songbird species to demonstrate how each of these concepts is limited. We discuss the solid evidence for steroid synthesis within the brain (“neurosteroidogenesis”), the role of neurosteroids in organizational events that occur both early in development and later in life, and how neurosteroids can act in acute and non-traditional ways. The songbird model therefore illustrates how neurosteroids can dramatically increase the diversity of steroid-sensitive brain functions in a behaviorally-relevant system. We hope this inspires further research and thought into neurosteroid signaling in songbirds and other animals. PMID:19442685
... healthy cells. The Merck Manual states the following: Radiation Injury to the Nervous System: The nervous system can be damaged by radiation therapy. Acute and subacute transient symptoms may develop early, but ...
Movement maintains forebrain neurogenesis via peripheral neural feedback in larval zebrafish
Hall, Zachary Jonas
2018-01-01
The postembryonic brain exhibits experience-dependent development, in which sensory experience guides normal brain growth. This neuroplasticity is thought to occur primarily through structural and functional changes in pre-existing neurons. Whether neurogenesis also mediates the effects of experience on brain growth is unclear. Here, we characterized the importance of motor experience on postembryonic neurogenesis in larval zebrafish. We found that movement maintains an expanded pool of forebrain neural precursors by promoting progenitor self-renewal over the production of neurons. Physical cues associated with swimming (bodily movement) increase neurogenesis and these cues appear to be conveyed by dorsal root ganglia (DRG) in the zebrafish body: DRG-deficient larvae exhibit attenuated neurogenic responses to movement and targeted photoactivation of DRG in immobilized larvae expands the pallial pool of proliferative cells. Our results demonstrate the importance of movement in neurogenic brain growth and reveal a fundamental sensorimotor association that may couple early motor and brain development. PMID:29528285
Causal Structure of Brain Physiology after Brain Injury from Subarachnoid Hemorrhage.
Claassen, Jan; Rahman, Shah Atiqur; Huang, Yuxiao; Frey, Hans-Peter; Schmidt, J Michael; Albers, David; Falo, Cristina Maria; Park, Soojin; Agarwal, Sachin; Connolly, E Sander; Kleinberg, Samantha
2016-01-01
High frequency physiologic data are routinely generated for intensive care patients. While massive amounts of data make it difficult for clinicians to extract meaningful signals, these data could provide insight into the state of critically ill patients and guide interventions. We develop uniquely customized computational methods to uncover the causal structure within systemic and brain physiologic measures recorded in a neurological intensive care unit after subarachnoid hemorrhage. While the data have many missing values, poor signal-to-noise ratio, and are composed from a heterogeneous patient population, our advanced imputation and causal inference techniques enable physiologic models to be learned for individuals. Our analyses confirm that complex physiologic relationships including demand and supply of oxygen underlie brain oxygen measurements and that mechanisms for brain swelling early after injury may differ from those that develop in a delayed fashion. These inference methods will enable wider use of ICU data to understand patient physiology.
Parent, Maxime; Li, Ying; Santhakumar, Vijayalakshmi; Hyder, Fahmeed; Sanganahalli, Basavaraju G; Kannurpatti, Sridhar
2018-06-01
TBI is a leading cause of morbidity in children. To investigate outcome of early developmental TBI during adolescence, a rat model of fluid percussion injury was developed, where previous work reported deficits in sensorimotor behavior and cortical blood flow at adolescence. 1 Based on the non-localized outcome, we hypothesized that multiple neurophysiological components of brain function, namely neuronal connectivity, synapse/axonal microstructural integrity and neurovascular function are altered and magnetic resonance imaging (MRI) methods could be used to determine regional alterations. Adolescent outcomes of developmental TBI were studied 2-months after injury, using functional MRI (fMRI) and Diffusion Tensor Imaging (DTI). fMRI based resting state functional connectivity (RSFC), representing neural connectivity, was significantly altered between sham and TBI. RSFC strength decreased in the cortex, hippocampus and thalamus accompanied by decrease in the spatial extent of their corresponding RSFC networks and inter-hemispheric asymmetry. Cerebrovascular reactivity to arterial CO2 changes diminished after TBI across both hemispheres, with a more pronounced decrease in the ipsilateral hippocampus, thalamus and motor cortex. DTI measures of fractional anisotropy (FA) and apparent diffusion coefficient (ADC), reporting on axonal and microstructural integrity of the brain, indicated similar inter-hemispheric asymmetry, with highest change in the ipsilateral hippocampus and regions adjoining the ipsilateral thalamus, hypothalamus and amygdala. TBI-induced corpus callosal microstructural alterations indicated measurable changes in inter-hemispheric structural connectivity. Hippocampus, thalamus and select cortical regions were most consistently affected in multiple imaging markers. The multi-modal MRI results demonstrate cortical and subcortical alterations in neural connectivity, cerebrovascular resistance and parenchymal microstructure in the adolescent brain, indicating the highly diffuse and persistent nature of the lateral fluid percussion TBI early in development.
Giving Latino Children a Stronger Start. New Journalism on Latino Children
ERIC Educational Resources Information Center
Rivera, Carla
2009-01-01
Early Head Start serves newborns through toddlers. It is an offshoot of Head Start, the 44-year-old federal program for low-income children ages 3 through 5. Social scientists studying brain development and emotional growth increasingly identify early education as critical to preparing children for kindergarten. As well, researchers have linked it…
Building on the Foundations of Part C Legislation: Beginning the Conversation for Reauthorization
ERIC Educational Resources Information Center
Cole, Patricia; Oser, Cindy; Walsh, Sharon
2011-01-01
Just as the early years of a child's development create the architecture for future brain growth, early implementation of federal Part C legislation laid the groundwork for a system of supports for families of infants and toddlers with disabilities. Some aspects of the current legislation provide a sturdy foundation for sound policies and…
Optimizing Infant Development: Strategies for Day Care.
ERIC Educational Resources Information Center
Chambliss, Catherine
This guide for infant day care providers examines the importance of early experience for brain development and strategies for providing optimal infant care. The introduction discusses the current devaluation of day care and idealization of maternal care and identifies benefits of quality day care experience for intellectual development, sleep…
Korevaar, Tim I M; Muetzel, Ryan; Medici, Marco; Chaker, Layal; Jaddoe, Vincent W V; de Rijke, Yolanda B; Steegers, Eric A P; Visser, Theo J; White, Tonya; Tiemeier, Henning; Peeters, Robin P
2016-01-01
Thyroid hormone is involved in the regulation of early brain development. Since the fetal thyroid gland is not fully functional until week 18-20 of pregnancy, neuronal migration and other crucial early stages of intrauterine brain development largely depend on the supply of maternal thyroid hormone. Current clinical practice mostly focuses on preventing the negative consequences of low thyroid hormone concentrations, but data from animal studies have shown that both low and high concentrations of thyroid hormone have negative effects on offspring brain development. We aimed to investigate the association of maternal thyroid function with child intelligence quotient (IQ) and brain morphology. In this population-based prospective cohort study, embedded within the Generation R Study (Rotterdam, Netherlands), we investigated the association of maternal thyroid function with child IQ (assessed by non-verbal intelligence tests) and brain morphology (assessed on brain MRI scans). Eligible women were those living in the study area at their delivery date, which had to be between April 1, 2002, and Jan 1, 2006. For this study, women with available serum samples who presented in early pregnancy (<18 weeks) were included. Data for maternal thyroid-stimulating hormone, free thyroxine, thyroid peroxidase antibodies (at weeks 9-18 of pregnancy), and child IQ (assessed at a median of 6·0 years of age [95% range 5·6-7·9 years]) or brain MRI scans (done at a median of 8·0 years of age [6·2-10·0]) were obtained. Analyses were adjusted for potential confounders including concentrations of human chorionic gonadotropin and child thyroid-stimulating hormone and free thyroxine. Data for child IQ were available for 3839 mother-child pairs, and MRI scans were available from 646 children. Maternal free thyroxine concentrations showed an inverted U-shaped association with child IQ (p=0·0044), child grey matter volume (p=0·0062), and cortex volume (p=0·0011). For both low and high maternal free thyroxine concentrations, this association corresponded to a 1·4-3·8 points reduction in mean child IQ. Maternal thyroid-stimulating hormone was not associated with child IQ or brain morphology. All associations remained similar after the exclusion of women with overt hypothyroidism and overt hyperthyroidism, and after adjustment for concentrations of human chorionic gonadotropin, child thyroid-stimulating hormone and free thyroxine or thyroid peroxidase antibodies (continuous or positivity). Both low and high maternal free thyroxine concentrations during pregnancy were associated with lower child IQ and lower grey matter and cortex volume. The association between high maternal free thyroxine and low child IQ suggests that levothyroxine therapy during pregnancy, which is often initiated in women with subclinical hypothyroidism during pregnancy, might carry the potential risk of adverse child neurodevelopment outcomes when the aim of treatment is to achieve high-normal thyroid function test results. The Netherlands Organisation for Health Research and Development (ZonMw) and the European Community's Seventh Framework Programme. Copyright © 2016 Elsevier Ltd. All rights reserved.
D'Angiulli, Amedeo
2018-01-01
According to the latest estimates, about 2 billion children around the world are exposed to severe urban outdoor air pollution. Transdisciplinary, multi-method findings from epidemiology, developmental neuroscience, psychology, and pediatrics, show detrimental outcomes associated with pre- and postnatal exposure are found at all ages. Affected brain-related functions include perceptual and sensory information processing, intellectual and cognitive development, memory and executive functions, emotion and self-regulation, and academic achievement. Correspondingly, with the breakdown of natural barriers against entry and translocation of toxic particles in the brain, the most common structural changes are responses promoting neuroinflammation and indicating early neurodegenerative processes. In spite of the gaps in current scientific knowledge and the challenges posed by non-scientific issues that influence policy, the evidence invites the conclusion that urban outdoor air pollution is a serious threat to healthy brain development which may set the conditions for neurodegenerative diseases. Such evidence supports the perspective that urgent strategic precautionary actions, minimizing exposure and attenuating its effects, are needed to protect children and their brain development.
D’Angiulli, Amedeo
2018-01-01
According to the latest estimates, about 2 billion children around the world are exposed to severe urban outdoor air pollution. Transdisciplinary, multi-method findings from epidemiology, developmental neuroscience, psychology, and pediatrics, show detrimental outcomes associated with pre- and postnatal exposure are found at all ages. Affected brain-related functions include perceptual and sensory information processing, intellectual and cognitive development, memory and executive functions, emotion and self-regulation, and academic achievement. Correspondingly, with the breakdown of natural barriers against entry and translocation of toxic particles in the brain, the most common structural changes are responses promoting neuroinflammation and indicating early neurodegenerative processes. In spite of the gaps in current scientific knowledge and the challenges posed by non-scientific issues that influence policy, the evidence invites the conclusion that urban outdoor air pollution is a serious threat to healthy brain development which may set the conditions for neurodegenerative diseases. Such evidence supports the perspective that urgent strategic precautionary actions, minimizing exposure and attenuating its effects, are needed to protect children and their brain development. PMID:29670873
ERIC Educational Resources Information Center
Kertes, Darlene A.; Kamin, Hayley S.; Hughes, David A.; Rodney, Nicole C.; Bhatt, Samarth; Mulligan, Connie J.
2016-01-01
Exposure to stress early in life permanently shapes activity of the hypothalamic-pituitary-adrenocortical (HPA) axis and the brain. Prenatally, glucocorticoids pass through the placenta to the fetus with postnatal impacts on brain development, birth weight (BW), and HPA axis functioning. Little is known about the biological mechanisms by which…
Play, ADHD, and the Construction of the Social Brain: Should the First Class Each Day Be Recess?
ERIC Educational Resources Information Center
Panksepp, Jaak
2008-01-01
Because of the role of play in the epigenetic construction of social brain functions, the young of all mammalian species need su?fficient play. For the same reason, the nature of that play becomes an important social policy issue for early childhood development and education. Animal research on this topic indicates that play can facilitate the…
ERIC Educational Resources Information Center
Pivik, R. T.; Andres, Aline; Badger, Thomas M.
2011-01-01
Early post-natal nutrition influences later development, but there are no studies comparing brain function in healthy infants as a function of dietary intake even though the major infant diets differ significantly in nutrient composition. We studied brain responses (event-related potentials; ERPs) to speech sounds for infants who were fed either…
A Moving Child Is a Learning Child: How the Body Teaches the Brain to Think (Birth to Age 7)
ERIC Educational Resources Information Center
Connell, Gill; McCarthy, Cheryl
2014-01-01
Grounded in best practices and current research, this hands-on resource connects the dots that link brain activity, motor and sensory development, movement, and early learning. The expert authors unveil the Kinetic Scale: a visual map of the active learning needs of infants, toddlers, preschoolers, and primary graders that fits each child's…
ERIC Educational Resources Information Center
Riley, Richard W.
This paper comprises remarks of U.S. Secretary of Education Richard Riley at the Early Childhood Summit in Washington, D.C. on June 23, 2000. The paper notes the emergence of a national consensus about the value of early childhood education. The paper maintains that brain development research coupled with new research on how children learn to read…
Non-pharmacological biological treatment approaches to difficult-to-treat depression.
Fitzgerald, Paul B
2013-09-16
There has been substantial recent interest in novel brain stimulation treatments for difficult-to-treat depression. Electroconvulsive therapy (ECT) is a well established, effective treatment for severe depression. ECT's problematic side-effect profile and questions regarding optimal administration methods continue to be investigated. Magnetic seizure therapy, although very early in development, shows promise, with potentially similar efficacy to ECT but fewer side effects. Vagus nerve stimulation (VNS) and repetitive transcranial magnetic stimulation (rTMS) are clinically available in some countries. Limited research suggests VNS has potentially long-lasting antidepressant effects in a small group of patients. Considerable research supports the efficacy of rTMS. Both techniques require further study of optimal treatment parameters. Transcranial direct current stimulation may provide a low-cost antidepressant option if its efficacy is substantiated in larger samples. Deep brain stimulation is likely to remain reserved for patients with the most severe and difficult-to-treat depression, requiring further exploration of administration methods and its role in depression therapy. New and innovative forms of brain stimulation, including low-intensity ultrasound, low-field magnetic stimulation and epidural stimulation of the cortical surface, are in early stages of exploration and are yet to move into the clinical domain. Ongoing work is required to define which brain stimulation treatments are likely to be most useful, and in which patient groups. Clinical service development of brain stimulation treatments will likely be inconsistent and variable.
Okamura, Nobuyuki; Mori, Masanori; Furumoto, Shozo; Yoshikawa, Takeo; Harada, Ryuichi; Ito, Satoshi; Fujikawa, Yosuke; Arai, Hiroyuki; Yanai, Kazuhiko; Kudo, Yukitsuka
2011-01-01
Noninvasive detection of amyloid-β (Aβ) deposits in the brain would be beneficial for an early and presymptomatic diagnosis of Alzheimer's disease (AD). We developed THK-265 as a candidate near-infrared fluorescence (NIRF) probe for the in vivo detection of amyloid deposits in the brain. The maximal emission wavelength of THK-265 was greater than 650nm and it showed high quantum yield and molar absorption coefficients. A fluorescence binding assay showed its high binding affinity to Aβ fibrils (Kd = 97 nM). THK-265 clearly stained amyloid plaques in AD neocortical brain sections and showed a moderate log p value (1.8). After intravenous administration of THK-265 in amyloid-β protein precursor (AβPP) transgenic mice, amyloid deposits in the brain were clearly labeled with THK-265. Furthermore, in vivo NIRF imaging demonstrated significantly higher fluorescence intensity in the brains of AβPP transgenic mice than in those of wild-type mice. As THK-265 showed profound hyperchromic effect upon binding to Aβ fibrils, good discrimination between AβPP transgenic and wild-type mice was demonstrated even early after THK-265 administration. Furthermore, the fluorescence intensity of THK-265 correlated with amyloid plaque burden in the brains of AβPP transgenic mice. These findings strongly support the usefulness of THK-265 as an NIRF imaging probe for the noninvasive measurement of brain amyloid load.
Henninger, Nils; Bouley, James; Sikoglu, Elif M; An, Jiyan; Moore, Constance M; King, Jean A; Bowser, Robert; Freeman, Marc R; Brown, Robert H
2016-04-01
Axonal degeneration is a critical, early event in many acute and chronic neurological disorders. It has been consistently observed after traumatic brain injury, but whether axon degeneration is a driver of traumatic brain injury remains unclear. Molecular pathways underlying the pathology of traumatic brain injury have not been defined, and there is no efficacious treatment for traumatic brain injury. Here we show that mice lacking the mouse Toll receptor adaptor Sarm1 (sterile α/Armadillo/Toll-Interleukin receptor homology domain protein) gene, a key mediator of Wallerian degeneration, demonstrate multiple improved traumatic brain injury-associated phenotypes after injury in a closed-head mild traumatic brain injury model. Sarm1(-/-) mice developed fewer β-amyloid precursor protein aggregates in axons of the corpus callosum after traumatic brain injury as compared to Sarm1(+/+) mice. Furthermore, mice lacking Sarm1 had reduced plasma concentrations of the phophorylated axonal neurofilament subunit H, indicating that axonal integrity is maintained after traumatic brain injury. Strikingly, whereas wild-type mice exibited a number of behavioural deficits after traumatic brain injury, we observed a strong, early preservation of neurological function in Sarm1(-/-) animals. Finally, using in vivo proton magnetic resonance spectroscopy we found tissue signatures consistent with substantially preserved neuronal energy metabolism in Sarm1(-/-) mice compared to controls immediately following traumatic brain injury. Our results indicate that the SARM1-mediated prodegenerative pathway promotes pathogenesis in traumatic brain injury and suggest that anti-SARM1 therapeutics are a viable approach for preserving neurological function after traumatic brain injury. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
Iron assessment to protect the developing brain.
Georgieff, Michael K
2017-12-01
Iron deficiency (ID) before the age of 3 y can lead to long-term neurological deficits despite prompt diagnosis of ID anemia (IDA) by screening of hemoglobin concentrations followed by iron treatment. Furthermore, pre- or nonanemic ID alters neurobehavioral function and is 3 times more common than IDA in toddlers. Given the global prevalence of ID and the enormous societal cost of developmental disabilities across the life span, better methods are needed to detect the risk of inadequate concentrations of iron for brain development (i.e., brain tissue ID) before dysfunction occurs and to monitor its amelioration after diagnosis and treatment. The current screening and treatment strategy for IDA fails to achieve this goal for 3 reasons. First, anemia is the final state in iron depletion. Thus, the developing brain is already iron deficient when IDA is diagnosed owing to the prioritization of available iron to red blood cells over all other tissues during negative iron balance in development. Second, brain ID, independently of IDA, is responsible for long-term neurological deficits. Thus, starting iron treatment after the onset of IDA is less effective than prevention. Multiple studies in humans and animal models show that post hoc treatment strategies do not reliably prevent ID-induced neurological deficits. Third, most currently used indexes of ID are population statistical cutoffs for either hematologic or iron status but are not bioindicators of brain ID and brain dysfunction in children. Furthermore, their relation to brain iron status is not known. To protect the developing brain, there is a need to generate serum measures that index brain dysfunction in the preanemic stage of ID, assess the ability of standard iron indicators to detect ID-induced brain dysfunction, and evaluate the efficacy of early iron treatment in preventing ID-induced brain dysfunction. © 2017 American Society for Nutrition.
Sex differences and structural brain maturation from childhood to early adulthood.
Koolschijn, P Cédric M P; Crone, Eveline A
2013-07-01
Recent advances in structural brain imaging have demonstrated that brain development continues through childhood and adolescence. In the present cross-sectional study, structural MRI data from 442 typically developing individuals (range 8-30) were analyzed to examine and replicate the relationship between age, sex, brain volumes, cortical thickness and surface area. Our findings show differential patterns for subcortical and cortical areas. Analysis of subcortical volumes showed that putamen volume decreased with age and thalamus volume increased with age. Independent of age, males demonstrated larger amygdala and thalamus volumes compared to females. Cerebral white matter increased linearly with age, at a faster pace for females than males. Gray matter showed nonlinear decreases with age. Sex-by-age interactions were primarily found in lobar surface area measurements, with males demonstrating a larger cortical surface up to age 15, while cortical surface in females remained relatively stable with increasing age. The current findings replicate some, but not all prior reports on structural brain development, which calls for more studies with large samples, replications, and specific tests for brain structural changes. In addition, the results point toward an important role for sex differences in brain development, specifically during the heterogeneous developmental phase of puberty. Copyright © 2013 Elsevier Ltd. All rights reserved.
Development of Human Brain Structural Networks Through Infancy and Childhood
Huang, Hao; Shu, Ni; Mishra, Virendra; Jeon, Tina; Chalak, Lina; Wang, Zhiyue J.; Rollins, Nancy; Gong, Gaolang; Cheng, Hua; Peng, Yun; Dong, Qi; He, Yong
2015-01-01
During human brain development through infancy and childhood, microstructural and macrostructural changes take place to reshape the brain's structural networks and better adapt them to sophisticated functional and cognitive requirements. However, structural topological configuration of the human brain during this specific development period is not well understood. In this study, diffusion magnetic resonance image (dMRI) of 25 neonates, 13 toddlers, and 25 preadolescents were acquired to characterize network dynamics at these 3 landmark cross-sectional ages during early childhood. dMRI tractography was used to construct human brain structural networks, and the underlying topological properties were quantified by graph-theory approaches. Modular organization and small-world attributes are evident at birth with several important topological metrics increasing monotonically during development. Most significant increases of regional nodes occur in the posterior cingulate cortex, which plays a pivotal role in the functional default mode network. Positive correlations exist between nodal efficiencies and fractional anisotropy of the white matter traced from these nodes, while correlation slopes vary among the brain regions. These results reveal substantial topological reorganization of human brain structural networks through infancy and childhood, which is likely to be the outcome of both heterogeneous strengthening of the major white matter tracts and pruning of other axonal fibers. PMID:24335033
Serag, Ahmed; Wilkinson, Alastair G.; Telford, Emma J.; Pataky, Rozalia; Sparrow, Sarah A.; Anblagan, Devasuda; Macnaught, Gillian; Semple, Scott I.; Boardman, James P.
2017-01-01
Quantitative volumes from brain magnetic resonance imaging (MRI) acquired across the life course may be useful for investigating long term effects of risk and resilience factors for brain development and healthy aging, and for understanding early life determinants of adult brain structure. Therefore, there is an increasing need for automated segmentation tools that can be applied to images acquired at different life stages. We developed an automatic segmentation method for human brain MRI, where a sliding window approach and a multi-class random forest classifier were applied to high-dimensional feature vectors for accurate segmentation. The method performed well on brain MRI data acquired from 179 individuals, analyzed in three age groups: newborns (38–42 weeks gestational age), children and adolescents (4–17 years) and adults (35–71 years). As the method can learn from partially labeled datasets, it can be used to segment large-scale datasets efficiently. It could also be applied to different populations and imaging modalities across the life course. PMID:28163680
Briken, Peer; Habermann, Niels; Berner, Wolfgang; Hill, Andreas
2005-09-01
The aim of this study was to investigate the number and type of brain abnormalities and their influence on psychosocial development, criminal history and paraphilias in sexual murderers. We analyzed psychiatric court reports of 166 sexual murderers and compared a group with notable signs of brain abnormalities (N = 50) with those without any signs (N = 116). Sexual murderers with brain abnormalities suffered more from early behavior problems. They were less likely to cohabitate with the victim at the time of the homicide and had more victims at the age of six years or younger. Psychiatric diagnoses revealed a higher total number of paraphilias: Transvestic fetishism and paraphilias not otherwise specified were more frequent in offenders with brain abnormalities. A binary logistic regression identified five predictors that accounted for 46.8% of the variance explaining the presence of brain abnormalities. Our results suggest the importance of a comprehensive neurological and psychological examination of this special offender group.
Guo, Ting; Winterburn, Julie L; Pipitone, Jon; Duerden, Emma G; Park, Min Tae M; Chau, Vann; Poskitt, Kenneth J; Grunau, Ruth E; Synnes, Anne; Miller, Steven P; Mallar Chakravarty, M
2015-01-01
The hippocampus, a medial temporal lobe structure central to learning and memory, is particularly vulnerable in preterm-born neonates. To date, segmentation of the hippocampus for preterm-born neonates has not yet been performed early-in-life (shortly after birth when clinically stable). The present study focuses on the development and validation of an automatic segmentation protocol that is based on the MAGeT-Brain (Multiple Automatically Generated Templates) algorithm to delineate the hippocampi of preterm neonates on their brain MRIs acquired at not only term-equivalent age but also early-in-life. First, we present a three-step manual segmentation protocol to delineate the hippocampus for preterm neonates and apply this protocol on 22 early-in-life and 22 term images. These manual segmentations are considered the gold standard in assessing the automatic segmentations. MAGeT-Brain, automatic hippocampal segmentation pipeline, requires only a small number of input atlases and reduces the registration and resampling errors by employing an intermediate template library. We assess the segmentation accuracy of MAGeT-Brain in three validation studies, evaluate the hippocampal growth from early-in-life to term-equivalent age, and study the effect of preterm birth on the hippocampal volume. The first experiment thoroughly validates MAGeT-Brain segmentation in three sets of 10-fold Monte Carlo cross-validation (MCCV) analyses with 187 different groups of input atlases and templates. The second experiment segments the neonatal hippocampi on 168 early-in-life and 154 term images and evaluates the hippocampal growth rate of 125 infants from early-in-life to term-equivalent age. The third experiment analyzes the effect of gestational age (GA) at birth on the average hippocampal volume at early-in-life and term-equivalent age using linear regression. The final segmentations demonstrate that MAGeT-Brain consistently provides accurate segmentations in comparison to manually derived gold standards (mean Dice's Kappa > 0.79 and Euclidean distance <1.3 mm between centroids). Using this method, we demonstrate that the average volume of the hippocampus is significantly different (p < 0.0001) in early-in-life (621.8 mm(3)) and term-equivalent age (958.8 mm(3)). Using these differences, we generalize the hippocampal growth rate to 38.3 ± 11.7 mm(3)/week and 40.5 ± 12.9 mm(3)/week for the left and right hippocampi respectively. Not surprisingly, younger gestational age at birth is associated with smaller volumes of the hippocampi (p = 0.001). MAGeT-Brain is capable of segmenting hippocampi accurately in preterm neonates, even at early-in-life. Hippocampal asymmetry with a larger right side is demonstrated on early-in-life images, suggesting that this phenomenon has its onset in the 3rd trimester of gestation. Hippocampal volume assessed at the time of early-in-life and term-equivalent age is linearly associated with GA at birth, whereby smaller volumes are associated with earlier birth.
Guo, Ting; Winterburn, Julie L.; Pipitone, Jon; Duerden, Emma G.; Park, Min Tae M.; Chau, Vann; Poskitt, Kenneth J.; Grunau, Ruth E.; Synnes, Anne; Miller, Steven P.; Mallar Chakravarty, M.
2015-01-01
Introduction The hippocampus, a medial temporal lobe structure central to learning and memory, is particularly vulnerable in preterm-born neonates. To date, segmentation of the hippocampus for preterm-born neonates has not yet been performed early-in-life (shortly after birth when clinically stable). The present study focuses on the development and validation of an automatic segmentation protocol that is based on the MAGeT-Brain (Multiple Automatically Generated Templates) algorithm to delineate the hippocampi of preterm neonates on their brain MRIs acquired at not only term-equivalent age but also early-in-life. Methods First, we present a three-step manual segmentation protocol to delineate the hippocampus for preterm neonates and apply this protocol on 22 early-in-life and 22 term images. These manual segmentations are considered the gold standard in assessing the automatic segmentations. MAGeT-Brain, automatic hippocampal segmentation pipeline, requires only a small number of input atlases and reduces the registration and resampling errors by employing an intermediate template library. We assess the segmentation accuracy of MAGeT-Brain in three validation studies, evaluate the hippocampal growth from early-in-life to term-equivalent age, and study the effect of preterm birth on the hippocampal volume. The first experiment thoroughly validates MAGeT-Brain segmentation in three sets of 10-fold Monte Carlo cross-validation (MCCV) analyses with 187 different groups of input atlases and templates. The second experiment segments the neonatal hippocampi on 168 early-in-life and 154 term images and evaluates the hippocampal growth rate of 125 infants from early-in-life to term-equivalent age. The third experiment analyzes the effect of gestational age (GA) at birth on the average hippocampal volume at early-in-life and term-equivalent age using linear regression. Results The final segmentations demonstrate that MAGeT-Brain consistently provides accurate segmentations in comparison to manually derived gold standards (mean Dice's Kappa > 0.79 and Euclidean distance <1.3 mm between centroids). Using this method, we demonstrate that the average volume of the hippocampus is significantly different (p < 0.0001) in early-in-life (621.8 mm3) and term-equivalent age (958.8 mm3). Using these differences, we generalize the hippocampal growth rate to 38.3 ± 11.7 mm3/week and 40.5 ± 12.9 mm3/week for the left and right hippocampi respectively. Not surprisingly, younger gestational age at birth is associated with smaller volumes of the hippocampi (p = 0.001). Conclusions MAGeT-Brain is capable of segmenting hippocampi accurately in preterm neonates, even at early-in-life. Hippocampal asymmetry with a larger right side is demonstrated on early-in-life images, suggesting that this phenomenon has its onset in the 3rd trimester of gestation. Hippocampal volume assessed at the time of early-in-life and term-equivalent age is linearly associated with GA at birth, whereby smaller volumes are associated with earlier birth. PMID:26740912
Statistical distribution of blood serotonin as a predictor of early autistic brain abnormalities
Janušonis, Skirmantas
2005-01-01
Background A wide range of abnormalities has been reported in autistic brains, but these abnormalities may be the result of an earlier underlying developmental alteration that may no longer be evident by the time autism is diagnosed. The most consistent biological finding in autistic individuals has been their statistically elevated levels of 5-hydroxytryptamine (5-HT, serotonin) in blood platelets (platelet hyperserotonemia). The early developmental alteration of the autistic brain and the autistic platelet hyperserotonemia may be caused by the same biological factor expressed in the brain and outside the brain, respectively. Unlike the brain, blood platelets are short-lived and continue to be produced throughout the life span, suggesting that this factor may continue to operate outside the brain years after the brain is formed. The statistical distributions of the platelet 5-HT levels in normal and autistic groups have characteristic features and may contain information about the nature of this yet unidentified factor. Results The identity of this factor was studied by using a novel, quantitative approach that was applied to published distributions of the platelet 5-HT levels in normal and autistic groups. It was shown that the published data are consistent with the hypothesis that a factor that interferes with brain development in autism may also regulate the release of 5-HT from gut enterochromaffin cells. Numerical analysis revealed that this factor may be non-functional in autistic individuals. Conclusion At least some biological factors, the abnormal function of which leads to the development of the autistic brain, may regulate the release of 5-HT from the gut years after birth. If the present model is correct, it will allow future efforts to be focused on a limited number of gene candidates, some of which have not been suspected to be involved in autism (such as the 5-HT4 receptor gene) based on currently available clinical and experimental studies. PMID:16029508
Statistical distribution of blood serotonin as a predictor of early autistic brain abnormalities.
Janusonis, Skirmantas
2005-07-19
A wide range of abnormalities has been reported in autistic brains, but these abnormalities may be the result of an earlier underlying developmental alteration that may no longer be evident by the time autism is diagnosed. The most consistent biological finding in autistic individuals has been their statistically elevated levels of 5-hydroxytryptamine (5-HT, serotonin) in blood platelets (platelet hyperserotonemia). The early developmental alteration of the autistic brain and the autistic platelet hyperserotonemia may be caused by the same biological factor expressed in the brain and outside the brain, respectively. Unlike the brain, blood platelets are short-lived and continue to be produced throughout the life span, suggesting that this factor may continue to operate outside the brain years after the brain is formed. The statistical distributions of the platelet 5-HT levels in normal and autistic groups have characteristic features and may contain information about the nature of this yet unidentified factor. The identity of this factor was studied by using a novel, quantitative approach that was applied to published distributions of the platelet 5-HT levels in normal and autistic groups. It was shown that the published data are consistent with the hypothesis that a factor that interferes with brain development in autism may also regulate the release of 5-HT from gut enterochromaffin cells. Numerical analysis revealed that this factor may be non-functional in autistic individuals. At least some biological factors, the abnormal function of which leads to the development of the autistic brain, may regulate the release of 5-HT from the gut years after birth. If the present model is correct, it will allow future efforts to be focused on a limited number of gene candidates, some of which have not been suspected to be involved in autism (such as the 5-HT4 receptor gene) based on currently available clinical and experimental studies.
Swain, J E; Kim, P; Spicer, J; Ho, S S; Dayton, C J; Elmadih, A; Abel, K M
2014-09-11
Brain networks that govern parental response to infant signals have been studied with imaging techniques over the last 15 years. The complex interaction of thoughts and behaviors required for sensitive parenting enables the formation of each individual's first social bonds and critically shapes development. This review concentrates on magnetic resonance imaging experiments which directly examine the brain systems involved in parental responses to infant cues. First, we introduce themes in the literature on parental brain circuits studied to date. Next, we present a thorough chronological review of state-of-the-art fMRI studies that probe the parental brain with a range of baby audio and visual stimuli. We also highlight the putative role of oxytocin and effects of psychopathology, as well as the most recent work on the paternal brain. Taken together, a new model emerges in which we propose that cortico-limbic networks interact to support parental brain responses to infants. These include circuitry for arousal/salience/motivation/reward, reflexive/instrumental caring, emotion response/regulation and integrative/complex cognitive processing. Maternal sensitivity and the quality of caregiving behavior are likely determined by the responsiveness of these circuits during early parent-infant experiences. The function of these circuits is modifiable by current and early-life experiences, hormonal and other factors. Severe deviation from the range of normal function in these systems is particularly associated with (maternal) mental illnesses - commonly, depression and anxiety, but also schizophrenia and bipolar disorder. Finally, we discuss the limits and extent to which brain imaging may broaden our understanding of the parental brain given our current model. Developments in the understanding of the parental brain may have profound implications for long-term outcomes in families across risk, resilience and possible interventions. This article is part of a Special Issue entitled Oxytocin and Social Behav. Copyright © 2014 Elsevier B.V. All rights reserved.
Autism as an adaptive common variant pathway for human brain development.
Johnson, Mark H
2017-06-01
While research on focal perinatal lesions has provided evidence for recovery of function, much less is known about processes of brain adaptation resulting from mild but widespread disturbances to neural processing over the early years (such as alterations in synaptic efficiency). Rather than being viewed as a direct behavioral consequence of life-long neural dysfunction, I propose that autism is best viewed as the end result of engaging adaptive processes during a sensitive period. From this perspective, autism is not appropriately described as a disorder of neurodevelopment, but rather as an adaptive common variant pathway of human functional brain development. Copyright © 2017 The Author. Published by Elsevier Ltd.. All rights reserved.
Cnossen, Maryse C; Scholten, Annemieke C; Lingsma, Hester F; Synnot, Anneliese; Haagsma, Juanita; Steyerberg, Prof Ewout W; Polinder, Suzanne
2017-01-01
Although major depressive disorder (MDD) and posttraumatic stress disorder (PTSD) are prevalent after traumatic brain injury (TBI), little is known about which patients are at risk for developing them. The authors systematically reviewed the literature on predictors and multivariable models for MDD and PTSD after TBI. The authors included 26 observational studies. MDD was associated with female gender, preinjury depression, postinjury unemployment, and lower brain volume, whereas PTSD was related to shorter posttraumatic amnesia, memory of the traumatic event, and early posttraumatic symptoms. Risk of bias ratings for most studies were acceptable, although studies that developed a multivariable model suffered from methodological shortcomings.
Özçalışkan, Şeyda; Levine, Susan C.; Goldin-Meadow, Susan
2013-01-01
Children with pre/perinatal unilateral brain lesions (PL) show remarkable plasticity for language development. Is this plasticity characterized by the same developmental trajectory that characterizes typically developing (TD) children, with gesture leading the way into speech? We explored this question, comparing 11 children with PL—matched to 30 TD children on expressive vocabulary—in the second year of life. Children with PL showed similarities to TD children for simple but not complex sentence types. Children with PL produced simple sentences across gesture and speech several months before producing them entirely in speech, exhibiting parallel delays in both gesture+speech and speech-alone. However, unlike TD children, children with PL produced complex sentence types first in speech-alone. Overall, the gesture-speech system appears to be a robust feature of language-learning for simple—but not complex—sentence constructions, acting as a harbinger of change in language development even when that language is developing in an injured brain. PMID:23217292
The development of hub architecture in the human functional brain network.
Hwang, Kai; Hallquist, Michael N; Luna, Beatriz
2013-10-01
Functional hubs are brain regions that play a crucial role in facilitating communication among parallel, distributed brain networks. The developmental emergence and stability of hubs, however, is not well understood. The current study used measures of network topology drawn from graph theory to investigate the development of functional hubs in 99 participants, 10-20 years of age. We found that hub architecture was evident in late childhood and was stable from adolescence to early adulthood. Connectivity between hub and non-hub ("spoke") regions, however, changed with development. From childhood to adolescence, the strength of connections between frontal hubs and cortical and subcortical spoke regions increased. From adolescence to adulthood, hub-spoke connections with frontal hubs were stable, whereas connectivity between cerebellar hubs and cortical spoke regions increased. Our findings suggest that a developmentally stable functional hub architecture provides the foundation of information flow in the brain, whereas connections between hubs and spokes continue to develop, possibly supporting mature cognitive function.
Shapira, Niva
2009-01-01
Though eggs have the unique capacity, like breastmilk, to concentrate essential nutrients required for early growth and brain development of offspring - i.e. n-3 PUFA, increasingly deficient and sources contaminated - cholesterol and allergy concerns often exclude them from perinatal recommendations. Egg's potential contribution of key nutrients required for peak brain development are re-evaluated vis-à-vis fortification, accessibility, and risks. Contributions of standard (USDA) and fortified (selected market-available) egg compositions to perinatal requirements for critical brain-supporting nutrients were compared to human and cow milks, and risks and recommendations evaluated. Standard egg has already higher concentrations/kcal of iron, selenium, zinc, choline, vitamins B12 and E, and essential amino acids (plus taurine) than human milk. Fortified egg could further yield significant n-3 PUFA % recommendations for pregnancy-lactation (total n-3 69.6-75.0% [DRI=1400-1300 mg/day]), including DHA (120.1-129.3%, mostly approximately 80% [calculated DRI=140-130 mg/day]), plus antioxidant vitamins A (9.0-15.2%) and E (51.6-65.3%), and minerals iodine (33.6-44.5%) and selenium (33.7-39.3%); % recommendations for children (1-3 y) even more. Cholesterol, important for nerve membranes and learning, may not be generally contraindicated in childbearing-aged women (approximately 10.5% hypercholesterolemia), and early-life egg exposure may increase tolerance. Egg-inclusive perinatal nutrition programs have shown significant contributions. Eggs, especially target-fortified, may provide a unique nutritional supplement for peak brain development continously during pregnancy, nursing, and infancy (from 6 months), especially vs. insufficiencies. Missing nutritional opportunities by egg exclusion vs. concerns of hypercholesterolemia or allergy could be addressed individually, rather than as general recommendations, warranting further research and targeted egg design.
Soares, Roberto O; Horiquini-Barbosa, Everton; Almeida, Sebastião S; Lachat, João-José
2017-09-29
As early protein malnutrition has a critically long-lasting impact on the hippocampal formation and its role in learning and memory, and environmental enrichment has demonstrated great success in ameliorating functional deficits, here we ask whether exposure to an enriched environment could be employed to prevent spatial memory impairment and neuroanatomical changes in the hippocampus of adult rats maintained on a protein deficient diet during brain development (P0-P35). To elucidate the protective effects of environmental enrichment, we used the Morris water task and neuroanatomical analysis to determine whether changes in spatial memory and number and size of CA1 neurons differed significantly among groups. Protein malnutrition and environmental enrichment during brain development had significant effects on the spatial memory and hippocampal anatomy of adult rats. Malnourished but non-enriched rats (MN) required more time to find the hidden platform than well-nourished but non-enriched rats (WN). Malnourished but enriched rats (ME) performed better than the MN and similarly to the WN rats. There was no difference between well-nourished but non-enriched and enriched rats (WE). Anatomically, fewer CA1 neurons were found in the hippocampus of MN rats than in those of WN rats. However, it was also observed that ME and WN rats retained a similar number of neurons. These results suggest that environmental enrichment during brain development alters cognitive task performance and hippocampal neuroanatomy in a manner that is neuroprotective against malnutrition-induced brain injury. These results could have significant implications for malnourished infants expected to be at risk of disturbed brain development. Copyright © 2017 Elsevier B.V. All rights reserved.
Neurobiological consequences of childhood trauma.
Nemeroff, Charles B
2004-01-01
There is considerable evidence to suggest that adverse early-life experiences have a profound effect on the developing brain. Neurobiological changes that occur in response to untoward early-life stress can lead to lifelong psychiatric sequelae. Children who are exposed to sexual or physical abuse or the death of a parent are at higher risk for development of depressive and anxiety disorders later in life. Preclinical and clinical studies have shown that repeated early-life stress leads to alterations in central neurobiological systems, particularly in the corticotropin-releasing factor system, leading to increased responsiveness to stress. Clearly, exposure to early-life stressors leads to neurobiological changes that increase the risk of psychopathology in both children and adults. Identification of the neurobiological substrates that are affected by adverse experiences in early life should lead to the development of more effective treatments for these disorders. The preclinical and clinical studies evaluating the consequences of early-life stress are reviewed.
Tristán-Noguero, Alba; Díez, Héctor; Jou, Cristina; Pineda, Mercè; Ormazábal, Aida; Sánchez, Aurora; Artuch, Rafael; Garcia-Cazorla, Àngels
2016-06-01
Tyrosine hydroxylase (TH) deficiency is an inborn error of dopamine synthesis. Two clinical phenotypes have been described. The THD "B" phenotype produces a severe encephalopathy of early-onset with sub-optimal L-Dopa response, whereas the "A" phenotype has a better L-Dopa response and outcome. The objective of the study is to describe the expression of key synaptic proteins and neurodevelopmental markers in a fetal brain of THD "B" phenotype. The brain of a 16-week-old miscarried human fetus was dissected in different brain areas and frozen until the analysis. TH gene study revealed the p.R328W/p.T399M mutations, the same mutations that produced a B phenotype in her sister. After protein extraction, western blot analyses were performed to assess protein expression. The results were compared to an age-matched control. We observed a decreased expression in TH and in other dopaminergic proteins, such as VMAT 1 and 2 and dopamine receptors, especially D2DR. GABAergic and glutamatergic proteins such as GABA VT, NMDAR1 and calbindin were also altered. Developmental markers for synapses, axons and dendrites were decreased whereas markers of neuronal volume were preserved. Although this is an isolated case, this brain sample is unique and corresponds to the first reported study of a THD brain. It provides interesting information about the influence of dopamine as a regulator of other neurotransmitter systems, brain development and movement disorders with origin at the embryological state. This study could also contribute to a better understanding of the pathophysiology of THD at early fetal stages.
Rohr, Christiane S; Vinette, Sarah A; Parsons, Kari A L; Cho, Ivy Y K; Dimond, Dennis; Benischek, Alina; Lebel, Catherine; Dewey, Deborah; Bray, Signe
2017-09-01
Early childhood is a period of profound neural development and remodeling during which attention skills undergo rapid maturation. Attention networks have been extensively studied in the adult brain, yet relatively little is known about changes in early childhood, and their relation to cognitive development. We investigated the association between age and functional connectivity (FC) within the dorsal attention network (DAN) and the association between FC and attention skills in early childhood. Functional magnetic resonance imaging data was collected during passive viewing in 44 typically developing female children between 4 and 7 years whose sustained, selective, and executive attention skills were assessed. FC of the intraparietal sulcus (IPS) and the frontal eye fields (FEF) was computed across the entire brain and regressed against age. Age was positively associated with FC between core nodes of the DAN, the IPS and the FEF, and negatively associated with FC between the DAN and regions of the default-mode network. Further, controlling for age, FC between the IPS and FEF was significantly associated with selective attention. These findings add to our understanding of early childhood development of attention networks and suggest that greater FC within the DAN is associated with better selective attention skills. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
Hypothyroidism during pregnancy and the early postnatal period has severe neurological consequences for the developing offspring. The impact of milder degrees of perturbation of the thyroid axis, typically considered subclinical, however, has not been established. Thyroid hormo...
Early Under-Nutrition and Mental Performance.
ERIC Educational Resources Information Center
Van Heerden, J. R.
1984-01-01
Reviews the effects of malnutrition during pregnancy and before the age of three on children's brain development and subsequent mental development. Describes marasmus, kwashiorkor, and the incidence of malnutrition in South Africa. Discusses the relationship between the culture of poverty, malnutrition, and illegitimacy. Urges South Africans to…
Responsive Infant Caregiving: Eight Proven Practices
ERIC Educational Resources Information Center
Leifield, Lisa; Sanders, Tisha Bennett
2007-01-01
Brain research has confirmed what many early care and education professionals have known all along--warm, nurturing relationships among babies, toddlers, and their caregivers support children's development. The nurturing adult-child interaction that supports children's development is called "responsive care". Responsive care is supported by small…
Pitts, Matthew W; Kremer, Penny M; Hashimoto, Ann C; Torres, Daniel J; Byrns, China N; Williams, Christopher S; Berry, Marla J
2015-11-18
Selenium (Se) is essential for both brain development and male fertility. Male mice lacking two key genes involved in Se metabolism (Scly(-/-)Sepp1(-/-) mice), selenoprotein P (Sepp1) and Sec lyase (Scly), develop severe neurological dysfunction, neurodegeneration, and audiogenic seizures that manifest beginning in early adulthood. We demonstrate that prepubescent castration of Scly(-/-)Sepp1(-/-) mice prevents behavioral deficits, attenuates neurodegeneration, rescues maturation of GABAergic inhibition, and increases brain selenoprotein levels. Moreover, castration also yields similar neuroprotective benefits to Sepp1(-/-) and wild-type mice challenged with Se-deficient diets. Our data show that, under Se-compromised conditions, the brain and testes compete for Se utilization, with concomitant effects on neurodevelopment and neurodegeneration. Selenium is an essential trace element that promotes male fertility and brain function. Herein, we report that prepubescent castration provides neuroprotection by increasing selenium-dependent antioxidant activity in the brain, revealing a competition between the brain and testes for selenium utilization. These findings provide novel insight into the interaction of sex and oxidative stress upon the developing brain and have potentially significant implications for the prevention of neurodevelopmental disorders characterized by aberrant excitatory/inhibitory balance, such as schizophrenia and epilepsy. Copyright © 2015 the authors 0270-6474/15/3515326-13$15.00/0.
Infant fMRI: A Model System for Cognitive Neuroscience.
Ellis, Cameron T; Turk-Browne, Nicholas B
2018-05-01
Our understanding of the typical human brain has benefitted greatly from studying different kinds of brains and their associated behavioral repertoires, including animal models and neuropsychological patients. This same comparative perspective can be applied to early development - the environment, behavior, and brains of infants provide a model system for understanding how the mature brain works. This approach requires noninvasive methods for measuring brain function in awake, behaving infants. fMRI is becoming increasingly viable for this purpose, with the unique ability to precisely measure the entire brain, including both cortical and subcortical structures. Here we discuss potential lessons from infant fMRI for several domains of adult cognition and consider the challenges of conducting such research and how they might be mitigated. Copyright © 2018 Elsevier Ltd. All rights reserved.
Gaining insight of fetal brain development with diffusion MRI and histology.
Huang, Hao; Vasung, Lana
2014-02-01
Human brain is extraordinarily complex and yet its origin is a simple tubular structure. Its development during the fetal period is characterized by a series of accurately organized events which underlie the mechanisms of dramatic structural changes during fetal development. Revealing detailed anatomy at different stages of human fetal brain development provides insight on understanding not only this highly ordered process, but also the neurobiological foundations of cognitive brain disorders such as mental retardation, autism, schizophrenia, bipolar and language impairment. Diffusion tensor imaging (DTI) and histology are complementary tools which are capable of delineating the fetal brain structures at both macroscopic and microscopic levels. In this review, the structural development of the fetal brains has been characterized with DTI and histology. Major components of the fetal brain, including cortical plate, fetal white matter and cerebral wall layer between the ventricle and subplate, have been delineated with DTI and histology. Anisotropic metrics derived from DTI were used to quantify the microstructural changes during the dynamic process of human fetal cortical development and prenatal development of other animal models. Fetal white matter pathways have been traced with DTI-based tractography to reveal growth patterns of individual white matter tracts and corticocortical connectivity. These detailed anatomical accounts of the structural changes during fetal period may provide the clues of detecting developmental and cognitive brain disorders at their early stages. The anatomical information from DTI and histology may also provide reference standards for diagnostic radiology of premature newborns. Copyright © 2013 ISDN. Published by Elsevier Ltd. All rights reserved.
Neural Development Under Conditions of Spaceflight
NASA Technical Reports Server (NTRS)
Kosik, Kenneth S.; Steward, Oswald; Temple, Meredith D.; Denslow, Maria J.
2003-01-01
One of the key tasks the developing brain must learn is how to navigate within the environment. This skill depends on the brain's ability to establish memories of places and things in the environment so that it can form cognitive maps. Earth's gravity defines the plane of orientation of the spatial environment in which animals navigate, and cognitive maps are based on this plane of orientation. Given that experience during early development plays a key role in the development of other aspects of brain function, experience in a gravitational environment is likely to be essential for the proper organization of brain regions mediating learning and memory of spatial information. Since the hippocampus is the brain region responsible for cognitive mapping abilities, this study evaluated the development of hippocampal structure and function in rats that spent part of their early development in microgravity. Litters of male and female Sprague-Dawley rats were launched into space aboard the Space Shuttle Columbia on either postnatal day eight (P8) or 14 (P14) and remained in space for 16 days. Upon return to Earth, the rats were tested for their ability to remember spatial information and navigate using a variety of tests (the Morris water maze, a modified radial arm maze, and an open field apparatus). These rats were then tested physiologically to determine whether they exhibited normal synaptic plasticity in the hippocampus. In a separate group of rats (flight and controls), the hippocampus was analyzed using anatomical, molecular biological, and biochemical techniques immediately postlanding. There were remarkably few differences between the flight groups and their Earth-bound controls in either the navigation and spatial memory tasks or activity-induced synaptic plasticity. Microscopic and immunocytochemical analyses of the brain also did not reveal differences between flight animals and ground-based controls. These data suggest that, within the developmental window studied, microgravity has minimal long-term impact on cognitive mapping function and cellular substrates important for this function. Any differences due to development in microgravity were transient and returned to normal soon after return to Earth.
Biallelic UFM1 and UFC1 mutations expand the essential role of ufmylation in brain development.
Nahorski, Michael S; Maddirevula, Sateesh; Ishimura, Ryosuke; Alsahli, Saud; Brady, Angela F; Begemann, Anaïs; Mizushima, Tsunehiro; Guzmán-Vega, Francisco J; Obata, Miki; Ichimura, Yoshinobu; Alsaif, Hessa S; Anazi, Shams; Ibrahim, Niema; Abdulwahab, Firdous; Hashem, Mais; Monies, Dorota; Abouelhoda, Mohamed; Meyer, Brian F; Alfadhel, Majid; Eyaid, Wafa; Zweier, Markus; Steindl, Katharina; Rauch, Anita; Arold, Stefan T; Woods, C Geoffrey; Komatsu, Masaaki; Alkuraya, Fowzan S
2018-06-02
The post-translational modification of proteins through the addition of UFM1, also known as ufmylation, plays a critical developmental role as revealed by studies in animal models. The recent finding that biallelic mutations in UBA5 (the E1-like enzyme for ufmylation) cause severe early-onset encephalopathy with progressive microcephaly implicates ufmylation in human brain development. More recently, a homozygous UFM1 variant was proposed as a candidate aetiology of severe early-onset encephalopathy with progressive microcephaly. Here, we establish a locus for severe early-onset encephalopathy with progressive microcephaly based on two families, and map the phenotype to a novel homozygous UFM1 mutation. This mutation has a significantly diminished capacity to form thioester intermediates with UBA5 and with UFC1 (the E2-like enzyme for ufmylation), with resulting impaired ufmylation of cellular proteins. Remarkably, in four additional families where eight children have severe early-onset encephalopathy with progressive microcephaly, we identified two biallelic UFC1 mutations, which impair UFM1-UFC1 intermediate formation with resulting widespread reduction of cellular ufmylation, a pattern similar to that observed with UFM1 mutation. The striking resemblance between UFM1- and UFC1-related clinical phenotype and biochemical derangements strongly argues for an essential role for ufmylation in human brain development. The hypomorphic nature of UFM1 and UFC1 mutations and the conspicuous depletion of biallelic null mutations in the components of this pathway in human genome databases suggest that it is necessary for embryonic survival, which is consistent with the embryonic lethal nature of knockout models for the orthologous genes.
Morona, Ruth; González, Agustín
2013-01-01
The present study represents a detailed spatiotemporal analysis of the localization of calbindin-D28k (CB) and calretinin (CR) immunoreactive structures in the brain of Xenopus laevis throughout development, conducted with the aim to correlate the onset of the immunoreactivity with the development of compartmentalization of distinct subdivisions recently identified in the brain of adult amphibians and primarily highlighted when analyzed within a segmental paradigm. CR and CB are expressed early in the brain and showed a progressively increasing expression throughout development, although transient expression in some neuronal subpopulations was also noted. Common and distinct characteristics in Xenopus, as compared with reported features during development in the brain of mammals, were observed. The development of specific regions in the forebrain such as the olfactory bulbs, the components of the basal ganglia and the amygdaloid complex, the alar and basal hypothalamic regions, and the distinct diencephalic neuromeres could be analyzed on the basis of the distinct expression of CB and CR in subregions. Similarly, the compartments of the mesencephalon and the main rhombencephalic regions, including the cerebellum, were differently highlighted by their specific content in CB and CR throughout development. Our results show the usefulness of the analysis of the distribution of these proteins as a tool in neuroanatomy to interpret developmental aspects of many brain regions. Copyright © 2012 Wiley Periodicals, Inc.
Kaiser, Anelis; Eppenberger, Leila S; Smieskova, Renata; Borgwardt, Stefan; Kuenzli, Esther; Radue, Ernst-Wilhelm; Nitsch, Cordula; Bendfeldt, Kerstin
2015-01-01
Numerous structural studies have established that experience shapes and reshapes the brain throughout a lifetime. The impact of early development, however, is still a matter of debate. Further clues may come from studying multilinguals who acquired their second language at different ages. We investigated adult multilinguals who spoke three languages fluently, where the third language was learned in classroom settings, not before the age of 9 years. Multilinguals exposed to two languages simultaneously from birth (SiM) were contrasted with multinguals who acquired their first two languages successively (SuM). Whole brain voxel based morphometry revealed that, relative to SuM, SiM have significantly lower gray matter volume in several language-associated cortical areas in both hemispheres: bilaterally in medial and inferior frontal gyrus, in the right medial temporal gyrus and inferior posterior parietal gyrus, as well as in the left inferior temporal gyrus. Thus, as shown by others, successive language learning increases the volume of language-associated cortical areas. In brains exposed early on and simultaneously to more than one language, however, learning of additional languages seems to have less impact. We conclude that - at least with respect to language acquisition - early developmental influences are maintained and have an effect on experience-dependent plasticity well into adulthood.
Automated brain computed tomographic densitometry of early ischemic changes in acute stroke
Stoel, Berend C.; Marquering, Henk A.; Staring, Marius; Beenen, Ludo F.; Slump, Cornelis H.; Roos, Yvo B.; Majoie, Charles B.
2015-01-01
Abstract. The Alberta Stroke Program Early CT score (ASPECTS) scoring method is frequently used for quantifying early ischemic changes (EICs) in patients with acute ischemic stroke in clinical studies. Varying interobserver agreement has been reported, however, with limited agreement. Therefore, our goal was to develop and evaluate an automated brain densitometric method. It divides CT scans of the brain into ASPECTS regions using atlas-based segmentation. EICs are quantified by comparing the brain density between contralateral sides. This method was optimized and validated using CT data from 10 and 63 patients, respectively. The automated method was validated against manual ASPECTS, stroke severity at baseline and clinical outcome after 7 to 10 days (NIH Stroke Scale, NIHSS) and 3 months (modified Rankin Scale). Manual and automated ASPECTS showed similar and statistically significant correlations with baseline NIHSS (R=−0.399 and −0.277, respectively) and with follow-up mRS (R=−0.256 and −0.272), except for the follow-up NIHSS. Agreement between automated and consensus ASPECTS reading was similar to the interobserver agreement of manual ASPECTS (differences <1 point in 73% of cases). The automated ASPECTS method could, therefore, be used as a supplementary tool to assist manual scoring. PMID:26158082
Neuroimaging biomarkers of preterm brain injury: toward developing the preterm connectome
Panigrahy, Ashok; Wisnowski, Jessica L.; Furtado, Andre; Lepore, Natasha; Paquette, Lisa; Bluml, Stefan
2013-01-01
For typically developing infants, the last trimester of fetal development extending into the first post-natal months is a period of rapid brain development. Infants who are born premature face significant risk of brain injury (e.g., intraventricular or germinal matrix hemorrhage and periventricular leukomalacia) from complications in the perinatal period and also potential long-term neurodevelopmental disabilities because these early injuries can interrupt normal brain maturation. Neuroimaging has played an important role in the diagnosis and management of the preterm infant. Both cranial US and conventional MRI techniques are useful in diagnostic and prognostic evaluation of preterm brain development and injury. Cranial US is highly sensitive for intraventricular hemorrhage IVH and provides prognostic information regarding cerebral palsy. Data are limited regarding the utility of MRI as a routine screening instrument for brain injury for all preterm infants. However, MRI might provide diagnostic or prognostic information regarding PVL and other types of preterm brain injury in the setting of specific clinical indications and risk factors. Further development of advanced MR techniques like volumetric MR imaging, diffusion tensor imaging, metabolic imaging (MR spectroscopy) and functional connectivity are necessary to provide additional insight into the molecular, cellular and systems processes that underlie brain development and outcome in the preterm infant. The adult concept of the “connectome” is also relevant in understanding brain networks that underlie the preterm brain. Knowledge of the preterm connectome will provide a framework for understanding preterm brain function and dysfunction, and potentially even a roadmap for brain plasticity. By combining conventional imaging techniques with more advanced techniques, neuroimaging findings will likely be used not only as diagnostic and prognostic tools, but also as biomarkers for long-term neurodevelopmental outcomes, instruments to assess the efficacy of neuroprotective agents and maneuvers in the NICU, and as screening instruments to appropriately select infants for longitudinal developmental interventions. PMID:22395719
Pancreas and gallbladder agenesis in a newborn with semilobar holoprosencephaly, a case report.
Hilbrands, Robert; Keymolen, Kathelijn; Michotte, Alex; Marichal, Miriam; Cools, Filip; Goossens, Anieta; Veld, Peter In't; De Schepper, Jean; Hattersley, Andrew; Heimberg, Harry
2017-05-19
Pancreatic agenesis is an extremely rare cause of neonatal diabetes mellitus and has enabled the discovery of several key transcription factors essential for normal pancreas and beta cell development. We report a case of a Caucasian female with complete pancreatic agenesis occurring together with semilobar holoprosencephaly (HPE), a more common brain developmental disorder. Clinical findings were later confirmed by autopsy, which also identified agenesis of the gallbladder. Although the sequences of a selected set of genes related to pancreas agenesis or HPE were wild-type, the patient's phenotype suggests a genetic defect that emerges early in embryonic development of brain, gallbladder and pancreas. Developmental defects of the pancreas and brain can occur together. Identifying the genetic defect may identify a novel key regulator in beta cell development.