Generation of Urine-Derived Induced Pluripotent Stem Cells and Cerebral Organoids for Modeling Down Syndrome.

Down syndrome (DS, or trisomy 21, T21), is the most common genetic cause of intellectual disability. Alterations in the complex process of cerebral cortex development contribute to the neurological deficits in DS, although the underlying molecular and cellular mechanisms are not completely understood. Human cerebral organoids (COs) derived from three-dimensional (3D) cultures of induced pluripotent stem cells (iPSCs) provide a new avenue for gaining a better understanding of DS neuropathology. In this study, we aimed to generate iPSCs from individuals with DS (T21-iPSCs) and euploid controls using urine-derived cells, which can be easily and noninvasively obtained from most individuals, and examine their ability to differentiate into neurons and astrocytes grown in monolayer cultures, as well as into 3D COs. We employed nonintegrating episomal vectors to generate urine-derived iPSC lines, and a simple-to-use system to produce COs with forebrain identity. We observed that both T21 and control urine-derived iPSC lines successfully differentiate into neurons and astrocytes in monolayer, as well as into COs that recapitulate early features of human cortical development, including organization of neural progenitor zones, programmed differentiation of excitatory and inhibitory neurons, and upper-and deep-layer cortical neurons as well as astrocytes. Our findings demonstrate for the first time the suitability of using urine-derived iPSC lines to produce COs for modeling DS.

Comparative brain analysis of wild and hatchery reared Mahseer (Tor putitora) relative to their body weight and length / Análise comparativa do cérebro de Mahseer (Tor putitora) selvagem e criado em incubatório em relação ao peso e comprimento corporal

The present study was aimed at comparing the brain size of mahseer (Tor putitora) in relation to their body weight and standard length, to investigate the potential impact of rearing environment on brain development in fish. The weight of the brain and three of its subdivisions cerebellum (CB), optic tectum (OT), and telencephalon (TC) were measured for both wild and hatchery-reared fish. The data was analysed using multiple analysis of covariance (MANCOVA), analysis of covariance (ANCOVA), and discriminate function analysis (DFA). We found the fish reared under hatchery conditions exhibit smaller brain size related to body weight, when compared to the wild ones. A significant (p<0.5) difference was observed in the length of CB and OT concerning the standard body length while no significant difference was found in TC of the fish from both the origins. The results of the current study highlight a logical assumption that neural deficiency affects the behaviour of fish, that's why the captive-reared fish show maladaptive response and face fitness decline when released to the natural environment for wild stock enhancement. The current study concluded that hatchery-reared fish exhibit variations in gross brain morphology as compared to their wild counterpart.

O presente estudo teve como objetivo comparar o tamanho do cérebro de mahseer (Tor putitora) em relação ao seu peso corporal e comprimento padrão, para investigar o impacto potencial do ambiente de criação no desenvolvimento do cérebro em peixes. O peso do cérebro e três de suas subdivisões — cerebelo (CB), tectum óptico (OT) e telencéfalo (TC) — foram medidos para peixes selvagens e criados em incubadoras. Os dados foram analisados usando análise múltipla de covariância (MANCOVA), análise de covariância (ANCOVA) e análise de função discriminante (DFA). Descobrimos que os peixes criados em condições de incubação apresentam menor tamanho do cérebro em relação ao peso corporal quando comparados aos selvagens. Uma diferença significativa (p <0,5) foi observada no comprimento do CB e OT em relação ao comprimento corporal padrão, enquanto nenhuma diferença significativa foi encontrada no CT dos peixes de ambas as origens. Os resultados do estudo atual destacam uma suposição lógica de que a deficiência neural afeta o comportamento dos peixes. É por isso que os peixes criados em cativeiro mostram uma resposta mal adaptativa e enfrentam declínio de aptidão quando liberados no ambiente natural para o aprimoramento do estoque selvagem. O estudo atual concluiu que os peixes criados em incubadoras exibem variações na morfologia cerebral bruta em comparação com suas contrapartes selvagens.

The effects of short time hyperoxia on glutamate concentration and glutamate transporters expressions in brain of neonatal rats.

Preterm infants often suffer from impaired postnatal brain development, and glutamate excitotoxicity is identified as a pivotal mechanism of hyperoxia-induced neurological abnormality. We aimed to investigate the effect of short time hyperoxia on glutamate homeostasis and glutamate transporters expressions in immature brain. Six-day-old (P6) rat pups were exposed to 80% oxygen for 24 h (the hyperoxia group) or placed in atmospheric air (the control group). The concentrations of glutamate and γ-aminobutyric acid (GABA) in immature cerebrum and cerebellum at P7, P14 and P21 were determined by ELISA. The mRNA levels of glutamate transporters including excitatory amino acid transporter 1 (EAAT1), EAAT2, EAAT3, vesicular glutamate transporter 1 (VGLUT1) and VGLUT2 in brain were determined by qPCR. Glutamate accumulation was induced by hyperoxia both in immature cerebrum and cerebellum at P7 but got gradually attenuated at P14 and P21, as evidenced by the changes of glutamate and GABA concentrations. Hyperoxia also induced sustained glutamatic oxidative stress in both cerebrum and cerebellum, as GSH (reduced glutathione) levels in the hyperoxia group were constantly higher than the control group at three examined time-points. Furthermore, at P7, the expressions of all glutamate transporters decreased in both cerebrum and cerebellum except that of EAAT1. At P21, VGLUT2 in cerebrum and EAAT1, EAAT3 and VGLUT2 in cerebellum still displayed significant decrease in expression levels upon hyperoxia stimulation. Taken together, our results indicate that hyperoxia induces glutamate accumulation in brain of rat pups, which is associated with increased oxidative stress and decreased expressions of glutamate transporters.

Prolonged activation of cytomegalovirus early gene e1-promoter exclusively in neurons during infection of the developing cerebrum.

The brain is the major target of congenital cytomegalovirus (CMV) infection. It is possible that neuron disorder in the developing brain is a critical factor in the development of neuropsychiatric diseases in later life. Previous studies using mouse model of murine CMV (MCMV) infection demonstrated that the viral early antigen (E1 as a product of e1 gene) persists in the postnatal neurons of the hippocampus (HP) and cerebral cortex (CX) after the disappearance of lytic infection from non-neuronal cells in the periventricular (PV) region. Furthermore, neuron-specific activation of the MCMV-e1-promoter (e1-pro) was found in the cerebrum of transgenic mice carrying the e1-pro-lacZ reporter construct. In this study, in order to elucidate the mechanisms of e1-pro activation in cerebral neurons during actual MCMV infection, we have generated the recombinant MCMV (rMCMV) carrying long e1-pro1373- or short e1-pro448-EGFP reporter constructs. The length of the former, 1373 nucleotides (nt), is similar to that of transgenic mice. rMCMVs and wild type MCMV did not significantly differed in terms of viral replication or E1 expression. rMCMV-infected mouse embryonic fibroblasts showed lytic infection and activation of both promoters, while virus-infected cerebral neurons in primary neuronal cultures demonstrated the non-lytic and persistent infection as well as the activation of e1-pro-1373, but not -448. In the rMCMV-infected postnatal cerebrum, lytic infection and the activation of both promoters were found in non-neuronal cells of the PV region until postnatal 8 days (P8), but these disappeared at P12, while the activation of e1-pro-1373, but not -448 appeared in HP and CX neurons at P8 and were prolonged exclusively in these neurons at P12, with preservation of the neuronal morphology. Therefore, e1-pro-448 is sufficient to activate E1 expression in non-neuronal cells, however, the upstream sequence from nt -449 to -1373 in e1-pro-1373 is supposed to work as an enhancer necessary for the neuron-specific activation of e1-pro, particularly around the second postnatal week. This unique activation of e1-pro in developing cerebral neurons may be an important factor in the neurodevelopmental disorders induced by congenital CMV infection.

Robust Hi-C Maps of Enhancer-Promoter Interactions Reveal the Function of Non-coding Genome in Neural Development and Diseases.

Genome-wide mapping of chromatin interactions at high resolution remains experimentally and computationally challenging. Here we used a low-input "easy Hi-C" protocol to map the 3D genome architecture in human neurogenesis and brain tissues and also demonstrated that a rigorous Hi-C bias-correction pipeline (HiCorr) can significantly improve the sensitivity and robustness of Hi-C loop identification at sub-TAD level, especially the enhancer-promoter (E-P) interactions. We used HiCorr to compare the high-resolution maps of chromatin interactions from 10 tissue or cell types with a focus on neurogenesis and brain tissues. We found that dynamic chromatin loops are better hallmarks for cellular differentiation than compartment switching. HiCorr allowed direct observation of cell-type- and differentiation-specific E-P aggregates spanning large neighborhoods, suggesting a mechanism that stabilizes enhancer contacts during development. Interestingly, we concluded that Hi-C loop outperforms eQTL in explaining neurological GWAS results, revealing a unique value of high-resolution 3D genome maps in elucidating the disease etiology.

Newborns and preterm infants at term equivalent age: A semi-quantitative assessment of cerebral maturity.

BACKGROUND AND PURPOSE: Currently available MRI scoring systems of cerebral maturation in term and preterm infant at term equivalent age do not include the changes of transient fetal compartments that persist to term age. We studied the visibility and the pattern of these structures in healthy term newborns compared to preterm infants at term equivalent age in order to investigate if they can be included in a new MRI score system. We hypothesized that transient fetal compartments are different in both groups, and that these differences can be characterized using the clinical T2-weighted MRIs. MATERIALS AND METHODS: Using 3T MRI T2-weighted brain sequences of 21 full-term and 41 preterm infants (< 32 weeks), scanned at term equivalent age, 3 raters independently scored the maturation level of 3 transient fetal compartments: the periventricular crossroads, von Monakow segments of the white matter, and the subplate compartment. These 3 new items were included in a scoring system along with validated parameters of brain maturation (germinal matrix, bands of migration, subarachnoid space and quality of gyrification). A cumulative maturity score was calculated separately for both groups of newborns by adding together each item. More mature were the brain structures, higher was the cumulative maturity score. RESULTS: Cumulative maturity score distinguished full-term from preterm infants (mean score 41/60 ± 1.4 versus 37/60 ± 2.5 points, p < 0.001), with an increase of 0.5 points for each supplemental gestational week at birth (r = 0.5, 95% CI 0.5 - 0.85). While a majority of transient fetal compartments were less mature in preterm group at term equivalent age, von Monakow segments of the white matter and subplate compartment presented a more advanced maturational stage in the preterm group compared to the term group. No subject had all scored items in the most mature state. Except a slight intra-rater agreement for von Monakow segment II, inter- and intra-rater agreements were moderate to excellent indicating the potential of the developed scoring system in routine clinical practice. CONCLUSION: Brain transient fetal structures can be assessed on regular T2-weighted MRI in newborns. Their appearance differs between term and preterm babies. However our results suggest a more complex situation, with both delayed and accelerated maturation pattern in preterm infants. It remains to be determined if these differences could be biomarkers of the future neurodevelopment of preterm infants.

Lzts1 controls both neuronal delamination and outer radial glial-like cell generation during mammalian cerebral development.

In the developing central nervous system, cell departure from the apical surface is the initial and fundamental step to form the 3D, organized architecture. Both delamination of differentiating cells and repositioning of progenitors to generate outer radial glial cells (oRGs) contribute to mammalian neocortical expansion; however, a comprehensive understanding of their mechanisms is lacking. Here, we demonstrate that Lzts1, a molecule associated with microtubule components, promotes both cell departure events. In neuronally committed cells, Lzts1 functions in apical delamination by altering apical junctional organization. In apical RGs (aRGs), Lzts1 expression is variable, depending on Hes1 expression levels. According to its differential levels, Lzts1 induces diverse RG behaviors: planar division, oblique divisions of aRGs that generate oRGs, and their mitotic somal translocation. Loss-of-function of lzts1 impairs all these cell departure processes. Thus, Lzts1 functions as a master modulator of cellular dynamics, contributing to increasing complexity of the cerebral architecture during evolution.

A three-wave longitudinal study of subcortical-cortical resting-state connectivity in adolescence: Testing age- and puberty-related changes.

Adolescence is the transitional period between childhood and adulthood, characterized by substantial changes in reward-driven behavior. Although reward-driven behavior is supported by subcortical-medial prefrontal cortex (PFC) connectivity, the development of these circuits is not well understood. Particularly, while puberty has been hypothesized to accelerate organization and activation of functional neural circuits, the relationship between age, sex, pubertal change, and functional connectivity has hardly been studied. Here, we present an analysis of resting-state functional connectivity between subcortical structures and the medial PFC, in 661 scans of 273 participants between 8 and 29 years, using a three-wave longitudinal design. Generalized additive mixed model procedures were used to assess the effects of age, sex, and self-reported pubertal status on connectivity between subcortical structures (nucleus accumbens, caudate, putamen, hippocampus, and amygdala) and cortical medial structures (dorsal anterior cingulate, ventral anterior cingulate, subcallosal cortex, frontal medial cortex). We observed an age-related strengthening of subcortico-subcortical and cortico-cortical connectivity. Subcortical-cortical connectivity, such as, between the nucleus accumbens-frontal medial cortex, and the caudate-dorsal anterior cingulate cortex, however, weakened across age. Model-based comparisons revealed that for specific connections pubertal development described developmental change better than chronological age. This was particularly the case for changes in subcortical-cortical connectivity and distinctively for boys and girls. Together, these findings indicate changes in functional network strengthening with pubertal development. These changes in functional connectivity may maximize the neural efficiency of interregional communication and set the stage for further inquiry of biological factors driving adolescent functional connectivity changes.

Physical Growth of the Contralateral Cerebrum is Preserved After Hemispherotomy in Childhood.

BACKGROUND: Hemispherotomy can be an effective treatment for refractory childhood epilepsy. However, the extent of postoperative brain development after hemispherotomy remains incompletely understood. This study aims to provide an anatomic foundation in assessing development of the contralateral hemisphere, by measuring volumetric growth after hemispherotomy. METHODS: Eleven patients with hemimegalencephaly, Rasmussen's encephalitis, and cerebral infarction who underwent hemispherotomy before age 12 years, an immediate preoperative magnetic resonance imaging, and at least three years of follow-up magnetic resonance imagings were retrospectively analyzed. The volume of the contralateral hemisphere was measured before and after surgery. Growth curves were compared with those of healthy individuals from an open database. The growth rate relative to the healthy individuals ("catch-up rate") was calculated. RESULTS: A positive volumetric growth of the contralateral hemisphere was observed across all pathologies. The hemimegalencephaly subgroup underwent hemispherotomy at the earliest time and had the largest postoperative growth rate, which exceeded that of healthy individuals. The Rasmussen subgroup underwent surgery at the second earliest time and had an intermediate growth rate, which was similar to that of healthy individuals. The infarction subgroup underwent surgery at the latest time and had the slowest growth rate, which was less than that of healthy individuals. CONCLUSIONS: The contralateral hemisphere continues to increase in volume after hemispherotomy in childhood. Further studies with a larger sample size and correlation with cognitive outcomes may aid in characterizing the prognosis after hemispherotomy.

Gliogenesis in the outer subventricular zone promotes enlargement and gyrification of the primate cerebrum.

The primate cerebrum is characterized by a large expansion of cortical surface area, the formation of convolutions, and extraordinarily voluminous subcortical white matter. It was recently proposed that this expansion is primarily driven by increased production of superficial neurons in the dramatically enlarged outer subventricular zone (oSVZ). Here, we examined the development of the parietal cerebrum in macaque monkey and found that, indeed, the oSVZ initially adds neurons to the superficial layers II and III, increasing their thickness. However, as the oSVZ grows in size, its output changes to production of astrocytes and oligodendrocytes, which in primates outnumber cerebral neurons by a factor of three. After the completion of neurogenesis around embryonic day (E) 90, when the cerebrum is still lissencephalic, the oSVZ enlarges and contains Pax6+/Hopx+ outer (basal) radial glial cells producing astrocytes and oligodendrocytes until after E125. Our data indicate that oSVZ gliogenesis, rather than neurogenesis, correlates with rapid enlargement of the cerebrum and development of convolutions, which occur concomitantly with the formation of cortical connections via the underlying white matter, in addition to neuronal growth, elaboration of dendrites, and amplification of neuropil in the cortex, which are primary factors in the formation of cerebral convolutions in primates.

Early-life and pubertal stress differentially modulate grey matter development in human adolescents.

Animal and human studies have shown that both early-life traumatic events and ongoing stress episodes affect neurodevelopment, however, it remains unclear whether and how they modulate normative adolescent neuro-maturational trajectories. We characterized effects of early-life (age 0-5) and ongoing stressors (age 14-17) on longitudinal changes (age 14 to17) in grey matter volume (GMV) of healthy adolescents (n = 37). Timing and stressor type were related to differential GMV changes. More personal early-life stressful events were associated with larger developmental reductions in GMV over anterior prefrontal cortex, amygdala and other subcortical regions; whereas ongoing stress from the adolescents' social environment was related to smaller reductions over the orbitofrontal and anterior cingulate cortex. These findings suggest that early-life stress accelerates pubertal development, whereas an adverse adolescent social environment disturbs brain maturation with potential mental health implications: delayed anterior cingulate maturation was associated with more antisocial traits - a juvenile precursor of psychopathy.

Predominio del "cerebro triádico" de acuerdo a niveles de desempeño estratégico de un grupo de trabajadores colombianos / Predominance of "triadic brain" according to levels of strategic performance of Colombian workers group

RESUMEN Introducción: Las organizaciones poseen herramientas válidas que ayudan al reconocimiento de los neurotalentos, proporcionando elementos de selección de personal y desarrollo estratégico. Objetivo: Evaluar el predominio cerebral de un grupo de trabajadores de acuerdo a su nivel de desempeño estratégico, basado en la teoría del "cerebro tríadico". Métodos: Estudio descriptivo-evaluativo, multicéntrico, enfoque cuantitativo, diseño no experimental realizado en una muestra de 68 trabajadores, de las ciudades de Sincelejo y Rioacha; seleccionados de manera no probabilística y que desempeñan actividades en diferentes niveles estratégicos. La recogida de datos se hizo mediante el test revelador del cociente mental tríadico diseñado por Waldemar De Gregory, el análisis se hizo mediante estadígrafos descriptivos. Resultados: La mayoría de trabajadores pertenece al sexo femenino (60 por ciento), desempeñan cargos misionales (73,8 por ciento), poseen predominancia de cerebro central (46,0 por ciento), escala de medición superior. Conclusiones: El predomino de cerebro tríadico corresponde al cerebro central con un nivel superior y desarrollo de actividades de nivel estratégico misional(AU)

ABSTRACT Introduction: Organizations have valid tools that help the recognition of nurotalentos providing elements of recruitment and strategic development. Objectives: Assess brain dominance of a group of workers according to their level of strategic performance, based on the theory of "Brain triadic". Methods: Evaluative descriptive, multicenter study, quantitative approach, no experimental design; conducted on a sample of 68 workers selected probabilistically and not engaged in activities at different strategic levels. Data collection was done by the developer test triadic mental quotient (RCMT) designed by Waldemar De Gregory. Results: Most workers are female (60 percent), missionary positions (73.8 percent), central brain predominance (46.0 percent) and higher measurement scale. Conclusions: predominance of the central brain, higher level and strategic level missionary activities evidenced(AU)

Biological determination of mental disorders: a discussion based on recent hypotheses from neuroscience. / A determinação biológica dos transtornos mentais: uma discussão a partir de teses neurocientíficas recentes.

Understanding the processes involved in the development of mental disorders has proven challenging ever since psychiatry was founded as a field. Neuroscience has provided new expectations that an explanation will be found for the development of mental disorders based on biological functioning alone. However, such a goal has not been that easy to achieve, and new hypotheses have begun to appear in neuroscience research. In this article we identify epigenetics, neurodevelopment, and plasticity as the principal avenues for a new understanding of the biology of mental phenomena. Genetic complexity, the environment's formative role, and variations in vulnerability involve important changes in the principal hypotheses on biological determination of mental disorders, suggesting a reconfiguration of the limits between the "social" and the "biological" in neuroscience research.

Smaller Cerebellar Growth and Poorer Neurodevelopmental Outcomes in Very Preterm Infants Exposed to Neonatal Morphine.

OBJECTIVE: To examine the relationship between morphine exposure and growth of the cerebellum and cerebrum in very preterm neonates from early in life to term-equivalent age, as well as to examine morphine exposure and brain volumes in relation to neurodevelopmental outcomes at 18 months corrected age (CA). STUDY DESIGN: A prospective cohort of 136 very preterm neonates (24-32 weeks gestational age) was serially scanned with magnetic resonance imaging near birth and at term-equivalent age for volumetric measurements of the cerebellum and cerebrum. Motor outcomes were assessed with the Peabody Developmental Motor Scales, Second Edition and cognitive outcomes with the Bayley Scales of Infant and Toddler Development, Third Edition at 18 months CA. Generalized least squares models and linear regression models were used to assess relationships between morphine exposure, brain volumes, and neurodevelopmental outcomes. RESULTS: A 10-fold increase in morphine exposure was associated with a 5.5% decrease in cerebellar volume, after adjustment for multiple clinical confounders and total brain volume (P = .04). When infants exposed to glucocorticoids were excluded, the association of morphine was more pronounced, with an 8.1% decrease in cerebellar volume. Morphine exposure was not associated with cerebral volume (P = .30). Greater morphine exposure also predicted poorer motor (P < .001) and cognitive outcomes (P = .006) at 18 months CA, an association mediated, in part, by slower brain growth. CONCLUSIONS: Morphine exposure in very preterm neonates is independently associated with impaired cerebellar growth in the neonatal period and poorer neurodevelopmental outcomes in early childhood. Alternatives to better manage pain in preterm neonates that optimize brain development and functional outcomes are urgently needed.

A determinação biológica dos transtornos mentais: uma discussão a partir de teses neurocientíficas recentes / La determinación biológica de los trastornos mentales: una discusión a partir de tesis neurocientíficas recientes / Biological determination of mental disorders: a discussion based on recent hypotheses from neuroscience

Resumo: A compreensão dos processos de formação dos transtornos mentais vem se mostrando desafiadora desde a fundação do campo psiquiátrico. O desenvolvimento das neurociências proporcionou novo fôlego à expectativa de encontrar estritamente no funcionamento biológico a explicação para o surgimento dos transtornos mentais. No entanto, tal objetivo não vem sendo alcançado com a esperada facilidade, de modo que novas hipóteses começam a se destacar nas pesquisas neurocientíficas. Neste artigo, identificamos as noções de epigenética, neurodesenvolvimento e plasticidade como os principais indicativos de um novo modo de compreender a biologia dos fenômenos mentais. A complexidade genética, o papel formativo do ambiente e as variações que caracterizam a vulnerabilidade implicam importantes modificações nas principais teses sobre a determinação biológica dos transtornos mentais, sugerindo uma reconfiguração dos limites entre o "social" e o "biológico" nas pesquisas em neurociências.

Resumen: La comprensión de los procesos de formación de los trastornos mentales ha representado un desafio desde que nació el campo de la psiquiatria. El desarrollo de las neurociencias proporcionó un nuevo aliento a la expectativa de encontrar, estrictamente en el funcionamiento biológico, la explicación para el surgimiento de los trastornos mentales. No obstante, tal objetivo no se alcanza con la esperada facilidad, de modo que nuevas hipótesis comienzan a destacarse en las investigaciones neurocientíficas. En este artículo, identificamos las nociones de epigenética, neurodesarrollo y plasticidad como los principales indicativos de un nuevo modo de comprender la biología de los fenómenos mentales. La complejidad genética, el papel formativo del ambiente y las variaciones que caracterizan la vulnerabilidad implican importantes modificaciones en las principales tesis sobre la determinación biológica de los trastornos mentales, sugiriendo una reconfiguración de los límites entre lo "social" y lo "biológico" en las investigaciones en neurociencias.

Abstract: Understanding the processes involved in the development of mental disorders has proven challenging ever since psychiatry was founded as a field. Neuroscience has provided new expectations that an explanation will be found for the development of mental disorders based on biological functioning alone. However, such a goal has not been that easy to achieve, and new hypotheses have begun to appear in neuroscience research. In this article we identify epigenetics, neurodevelopment, and plasticity as the principal avenues for a new understanding of the biology of mental phenomena. Genetic complexity, the environment's formative role, and variations in vulnerability involve important changes in the principal hypotheses on biological determination of mental disorders, suggesting a reconfiguration of the limits between the "social" and the "biological" in neuroscience research.

Posterior structural brain volumes differ in maltreated youth with and without chronic posttraumatic stress disorder.

Magnetic resonance imaging studies of maltreated children with posttraumatic stress disorder (PTSD) suggest that maltreatment-related PTSD is associated with adverse brain development. Maltreated youth resilient to chronic PTSD were not previously investigated and may elucidate neuromechanisms of the stress diathesis that leads to resilience to chronic PTSD. In this cross-sectional study, anatomical volumetric and corpus callosum diffusion tensor imaging measures were examined using magnetic resonance imaging in maltreated youth with chronic PTSD (N = 38), without PTSD (N = 35), and nonmaltreated participants (n = 59). Groups were sociodemographically similar. Participants underwent assessments for strict inclusion/exclusion criteria and psychopathology. Maltreated youth with PTSD were psychobiologically different from maltreated youth without PTSD and nonmaltreated controls. Maltreated youth with PTSD had smaller posterior cerebral and cerebellar gray matter volumes than did maltreated youth without PTSD and nonmaltreated participants. Cerebral and cerebellar gray matter volumes inversely correlated with PTSD symptoms. Posterior corpus callosum microstructure in pediatric maltreatment-related PTSD differed compared to maltreated youth without PTSD and controls. The group differences remained significant when controlling for psychopathology, numbers of Axis I disorders, and trauma load. Alterations of these posterior brain structures may result from a shared trauma-related mechanism or an inherent vulnerability that mediates the pathway from chronic PTSD to comorbidity.

A vision of graded hemispheric specialization.

Understanding the process by which the cerebral hemispheres reach their mature functional organization remains challenging. We propose a theoretical account in which, in the domain of vision, faces and words come to be represented adjacent to retinotopic cortex by virtue of the need to discriminate among homogeneous exemplars. Orthographic representations are further constrained to be proximal to typically left-lateralized language-related information to minimize connectivity length between visual and language areas. As reading is acquired, orthography comes to rely more heavily (albeit not exclusively) on the left fusiform region to bridge vision and language. Consequently, due to competition from emerging word representations, face representations that were initially bilateral become lateralized to the right fusiform region (albeit, again, not exclusively). We review recent research that describes constraints that give rise to this graded hemispheric arrangement. We then summarize empirical evidence from a variety of studies (behavioral, evoked response potential, functional imaging) across different populations (children, adolescents, and adults; left handers and individuals with developmental dyslexia) that supports the claims that hemispheric lateralization is graded rather than binary and that this graded organization emerges dynamically over the course of development. Perturbations of this system either during development or in adulthood provide further insights into the principles governing hemispheric organization.

Gross morphology of the brain of Pseudopimelodus bufonius (Valenciennes, 1840) (Siluriformes: Pseudopimelodidae)

The gross morphology of the brain of the pseudopimelodid Pseudopimelodus bufonius is described and compared with congeners. Observations were made on removed brains after elimination of bones from the top of the skull and severing of the cranial nerves and the spinal cord. Nine morphometric characters associated with the major subdivisions of the brain were identified, seven of which revealed significant differences among the species examined. The corpus cerebelli in all examined species of the genus is the largest structure of the brain. The behavior of the species of Pseudopimelodus is still unknown, but in other teleosts that condition is typically correlated with a higher degree of motor coordination. Relative size proportions of the tectum opticum, eminentia granularis, lobus facialis and lobus vagi, might be related to carnivory and an enhanced capacity for food selection.

A morfologia externa do encéfalo de Pseudopimelodus bufonius é descrita e comparada com seus congêneres. As análises foram feitas no cérebro removido após a eliminação dos ossos do topo da cabeça e secção dos nervos cranianos e cordão espinhal. Nove caracteres morfométricos foram obtidos das principais subdivisões do encéfalo, dos quais em sete ocorreram diferenças significativas entre as espécies. Em todas as espécies examinadas do gênero o corpus cerebelli é a maior estrutura do encéfalo. O comportamento das espécies de Pseudopimelodus ainda é desconhecido, mas em outros teleósteos esta característica é normalmente correlacionada com uma boa coordenação motora. Além disso, as proporções relativas do tectum opticum, eminentia granularis, lobus facialis e lobus vagi podem ser relacionadas a hábitos carnívoros e boa capacidade de selecionar alimentos.

Normal development of human brain white matter from infancy to early adulthood: a diffusion tensor imaging study.

Diffusion tensor imaging (DTI), which measures the magnitude of anisotropy of water diffusion in white matter, has recently been used to visualize and quantify parameters of neural tracts connecting brain regions. In order to investigate the developmental changes and sex and hemispheric differences of neural fibers in normal white matter, we used DTI to examine 52 healthy humans ranging in age from 2 months to 25 years. We extracted the following tracts of interest (TOIs) using the region of interest method: the corpus callosum (CC), cingulum hippocampus (CGH), inferior longitudinal fasciculus (ILF), and superior longitudinal fasciculus (SLF). We measured fractional anisotropy (FA), apparent diffusion coefficient (ADC), axial diffusivity (AD), and radial diffusivity (RD). Approximate values and changes in growth rates of all DTI parameters at each age were calculated and analyzed using LOESS (locally weighted scatterplot smoothing). We found that for all TOIs, FA increased with age, whereas ADC, AD and RD values decreased with age. The turning point of growth rates was at approximately 6 years. FA in the CC was greater than that in the SLF, ILF and CGH. Moreover, FA, ADC and AD of the splenium of the CC (sCC) were greater than in the genu of the CC (gCC), whereas the RD of the sCC was lower than the RD of the gCC. The FA of right-hemisphere TOIs was significantly greater than that of left-hemisphere TOIs. In infants, growth rates of both FA and RD were larger than those of AD. Our data show that developmental patterns differ by TOIs and myelination along with the development of white matter, which can be mainly expressed as an increase in FA together with a decrease in RD. These findings clarify the long-term normal developmental characteristics of white matter microstructure from infancy to early adulthood.