Language performance and brain volumes, asymmetry, and cortical thickness in children born extremely preterm.

BACKGROUND: Children born preterm are more prone to have language difficulties. Few studies focus on children born extremely preterm (EPT) and the structural differences in language-related regions between these children and children born at term. METHODS: Our study used T1-weighted magnetic resonance imaging (MRI) scans to calculate the brain volumetry, brain asymmetry, and cortical thickness of language-related regions in 50 children born EPT and 37 term-born controls at 10 years of age. The language abilities of 41 of the children born EPT and 29 term-born controls were then assessed at 12 years of age, using the Wechsler Intelligence Scale for Children, Fifth Edition and the Clinical Evaluations of Language Fundamentals, Fourth Edition. The differences between MRI parameters and their associations with language outcomes were compared in the two groups. RESULTS: Brain volume and cortical thickness of language-related regions were reduced in children born EPT, but volumetric asymmetry was not different between children born EPT and at term. In children born EPT the brain volume was related to language outcomes, prior to adjustments for full-scale IQ. CONCLUSIONS: These findings expand our understanding of the structural correlates underlying impaired language performance in children born with EPT. IMPACT: The article expands understanding of the structure-function relationship between magnetic resonance imaging measurements of language-related regions and language outcomes for children born extremely preterm beyond infancy. Most literature to date has focused on very preterm children, but the focus in this paper is on extreme prematurity and language outcomes. While the brain volume and cortical thickness of language-related regions were reduced in children born EPT only the volume, prior to adjustment for full-scale IQ, was associated with language outcomes. We found no differences in volumetric asymmetry between children born EPT and at term.

Increased Resting-State Functional Connectivity in Patients With Autoimmune Addison Disease.

CONTEXT: Individuals with autoimmune Addison disease (AAD) take replacement medication for the lack of adrenal-derived glucocorticoid (GC) and mineralocorticoid hormones from diagnosis. The brain is highly sensitive to these hormones, but the consequence of having AAD for brain health has not been widely addressed. OBJECTIVE: The present study compared resting-state functional connectivity (rs-fc) of the brain between individuals with AAD and healthy controls. METHODS: Fifty-seven patients with AAD (33 female) and 69 healthy controls (39 female), aged 19 to 43 years were scanned with 3-T magnetic resonance imaging (MRI). RESULTS: Independent component and subsequent dual regression analyses revealed that individuals with AAD had stronger rs-fc compared to controls in 3 networks: the bilateral orbitofrontal cortex (OFC), the left medial visual and left posterior default mode network. A higher GC replacement dose was associated with stronger rs-fc in a small part of the left OFC in patients. We did not find any clear associations between rs-fc and executive functions or mental fatigue. CONCLUSION: Our results suggest that having AAD affects the baseline functional organization of the brain and that current treatment strategies of AAD may be one risk factor.

Extreme prematurity and perinatal risk factors related to extremely preterm birth are associated with complex patterns of regional brain volume alterations at 10 years of age: a voxel-based morphometry study.

Objective: Structural brain volumetric differences have been investigated previously in very preterm children. However, children born extremely preterm, at the border of viability, have been studied to a lesser degree. Our group previously analyzed children born extremely preterm at term using voxel-based morphometry. In this study, we aimed to examine regional gray and white matter differences for children born extremely preterm derived from the same cohort during childhood. We also aimed to explore the effect of perinatal risk factors on brain volumes in the same group. Methods: At 10 years of age, 51 children born extremely preterm (before 27 weeks and 0 days) and 38 term-born controls with high-quality 3.0 Tesla magnetic resonance images were included. Statistical analyses using voxel-based morphometry were conducted on images that were normalized using age-specific templates, modulated, and smoothed. Analyses were also performed in stratified groups of children born extremely preterm in the absence or presence of perinatal risk factors that have previously been shown to be associated with volumetric differences at term. Results: We found volumetric decreases in gray and white matter in the temporal lobes, gray matter decreases in the precuneus gyri, and white matter decreases in the anterior cingulum for children born extremely preterm (all p < 0.001, and pfwe < 0.05). Gray and white matter increases were predominantly observed in the right posterior cingulum and occipital lobe (all p < 0.001, and pfwe < 0.05). Of the examined perinatal risk factors, intraventricular hemorrhage grades I-II compared with no intraventricular hemorrhage and patent ductus arteriosus ligation compared with no treated patent ductus arteriosus or patent ductus arteriosus treated with ibuprofen led to volumetric differences at 10 years of age (all p < 0.001, and pfwe < 0.05). Conclusions: Children born extremely preterm exhibit volumetric alterations in a pattern overlapping that previously found at term, where many regions with differences are the main hubs of higher order networks. Some, but not all, risk factors known to be associated with structural alterations at term were associated with alterations at 10 years of age.

Disrupted resting-sate brain network dynamics in children born extremely preterm.

The developing brain has to adapt to environmental and intrinsic insults after extremely preterm (EPT) birth. Ongoing maturational processes maximize their fit to the environment and this can provide a substrate for neurodevelopmental failures. Resting-state functional magnetic resonance imaging was used to scan 33 children born EPT, at < 27 weeks of gestational age, and 26 full-term controls at 10 years of age. We studied the capability of a brain area to propagate neural information (intrinsic ignition) and its variability across time (node-metastability). This framework was computed for the dorsal attention network (DAN), frontoparietal, default-mode network (DMN), and the salience, limbic, visual, and somatosensory networks. The EPT group showed reduced intrinsic ignition in the DMN and DAN, compared with the controls, and reduced node-metastability in the DMN, DAN, and salience networks. Intrinsic ignition and node-metastability values correlated with cognitive performance at 12 years of age in both groups, but only survived in the term group after adjustment. Preterm birth disturbed the signatures of functional brain organization at rest in 3 core high-order networks: DMN, salience, and DAN. Identifying vulnerable resting-state networks after EPT birth may lead to interventions that aim to rebalance brain function.

Brain activity during visuospatial working memory in congenital adrenal hyperplasia.

CONTEXT: Patients with congenital adrenal hyperplasia (CAH) require life-long replacement of cortisol. Problems with cognitive function, especially working memory, have previously been identified, but the long-term effects of this disease on brain function are unknown. OBJECTIVE: We investigate brain activity during working memory in CAH compared to controls. DESIGN, SETTING, AND PARTICIPANTS: Twenty-nine individuals with CAH (17 females) and 40 healthy controls (24 females), 16-33 years, from a single research institute, underwent functional magnetic resonance imaging while doing a verbal and visuospatial working memory task. RESULTS: Individuals with CAH responded faster on the verbal task. Although we found no differences in BOLD response over the whole group, there were significant interactions with sex: CAH males had increased activity in the bilateral lateral superior occipital cortex, left supramarginal and angular gyri, left precuneus, left posterior cingulate cortex and bilateral cerebellum during decoding of the visuospatial task, while females showed decreased activity in these regions. CONCLUSIONS: Long-term cortisol imbalances do not seem to have a major impact on the functional brain responses during working memory in CAH. However, activity of the left dorsal visual stream in particular might be affected depending on sex. As the task employed may have been relatively easy, larger studies using more complex tasks are needed to further investigate this.

Brain structure in autoimmune Addison's disease.

Long-term disturbances in cortisol levels might affect brain structure in individuals with autoimmune Addison's disease (AAD). This study investigated gray and white matter brain structure in a cohort of young adults with AAD. T1- and diffusion-weighted images were acquired for 52 individuals with AAD and 70 healthy controls, aged 19-43 years, using magnetic resonance imaging. Groups were compared on cortical thickness, surface area, cortical gray matter volume, subcortical volume (FreeSurfer), and white matter microstructure (FSL tract-based spatial statistics). Individuals with AAD had 4.3% smaller total brain volume. Correcting for head size, we did not find any regional structural differences, apart from reduced volume of the right superior parietal cortex in males with AAD. Within the patient group, a higher glucocorticoid (GC) replacement dose was associated with smaller total brain volume and smaller volume of the left lingual gyrus, left rostral anterior cingulate cortex, and right supramarginal gyrus. With the exception of smaller total brain volume and potential sensitivity of the parietal cortex to GC disturbances in men, brain structure seems relatively unaffected in young adults with AAD. However, the association between GC replacement dose and reduced brain volume may be reason for concern and requires follow-up study.

Leche materna deslactosada con la enzima beta galactosidasa para lactantes intolerantes / Leite materno sem lactose com a enzima beta-galactosidase para lactentes intolerantes / Lactose-free breast milk with the enzyme beta galactosidase for intolerant infants

Introducción: los bebés deben beneficiarse de la leche materna, incluso cuando presentan intolerancia a la lactosa. Por esto, se debe recurrir a la obtención de leche materna deslactosada. Objetivo: analizar el efecto de la enzima beta galactosidasa en la hidrólisis de la lactosa de leche materna madura para bebés clínicamente diagnosticados con intolerancia a la lactosa. Materiales y método: estudio exploratorio, descriptivo y explicativo. El contenido de lactosa se cuantificó desde el inicio hasta el final del tratamiento, controlando temperatura, tiempos y cantidad de enzima ß-galactosidasa adicionada en la leche materna. Se recolectaron 1000 ml de leche materna, obtenidos del Banco de Leche del Hospital General de Medellín (Antioquia, Colombia). Resultados: las muestras donadas se encontraban pasteurizadas y posteriormente fueron sometidas a la acción de la enzima lactasa. Se cuantificó el contenido de lactosa sin la enzima, reportando en promedio 6,34 mg/100 ml ± 0,23. El mayor aporte de lactosa obtenido posterior a la exposición a la enzima (30 minutos) fue de 6,07 mg/ml ± 0,35 (correspondiente a 95 % del contenido inicial), finalizando con un aporte de 0,35 % a una concentración de 0,4 % tras 24 horas, porcentaje que representa 95 % de la hidrólisis total en la leche materna. Conclusiones: en todas las muestras analizadas de diferentes madres se pudo obtener leche materna con bajas concentraciones de lactosa tras 24 horas de haber sido sometidas a la acción de ß-galactosidasa. Lo anterior se establece como una alternativa para los bebés intolerantes a la lactosa, que permitiría no privarlos de todos los beneficios que ofrece este alimento.

Introduction: Babies should benefit from breast milk, even when they are lactose intolerant. For this reason, parents should resort to obtaining lactose-free breast milk. Objective: To examine the effect of the enzyme ß-galactosidase on the hydrolysis of lactose in mature breast milk for babies clinically diagnosed with lactose intolerance. Materials and method: Exploratory, descriptive, and explanatory study. The lactose content was quantified from the beginning to the end of the treatment, controlling variables such as temperature, times, and the amount of ß-galactosidase enzyme added in breast milk. A total of 1000 ml of breast milk were obtained from the milk bank at Hospital General de Medellín (Antioquia, Colombia). Results: Donated samples were first pasteurized and subsequently subjected to the action of the enzyme lactase. The lactose content without the enzyme was quantified, reporting an average of 6.34 mg/100 mL±0.23. The highest contribution of lactose obtained after exposure to the enzyme was 6.07 mg/mL±0.35 (corresponding to 95% of the initial content), at 30 minutes, ending with a contribution of 0.35% at a concentration of 0.4% in 24 hours, percentage that represents 95% of total hydrolysis in breast milk. Conclusions: In all the examined samples from different mothers, it was possible to obtain breast milk with low concentrations of lactose 24 hours after these were exposed to the action of ß-galactosidase. This becomes an alternative for feeding lactose intolerant babies and not deprive them from all the benefits offered by breast milk.

Introdução: os bebês se devem beneficiar do leite materno, mesmo quando tenham intolerância à lactose, razão pela qual se deve recorrer à obtenção de leite materno sem lactose. Objetivo: analisar o efeito da enzima beta-galactosidase na hidrólise da lactose no leite materno maduro para bebês diagnosticados clinicamente com intolerância à lactose. Materiais e método: estudo exploratório, descritivo, explicativo. O teor de lactose foi quantificado do início ao fim do tratamento; temperatura, tempos e quantidade de enzima beta-galactosidase adicionada no leite materno foram controlados; foram coletados 1000ml de leite materno, obtidos no Banco de Leite do Hospital General de Medellín (Antioquia, Colômbia). VResultados: as amostras doadas foram pasteurizadas e posteriormente submetidas à ação da enzima lactase. O teor de lactose sem a enzima foi quantificado, relatando uma média de 6,34mg/100ml±0,23. A maior contribuição de lactose obtida após a exposição à enzima foi de 6,07mg/ml±0,35 (correspondendo a 95% do conteúdo inicial) em 30 minutos, finalizando com uma contribuição de 0,35% na concentração de 0,4% em 24 horas, percentual que representa 95% da hidrólise total no leite materno. Conclusões: em todas as amostras analisadas de diferentes mães, foi possível obter leite materno com baixas concentrações de lactose 24 horas após ser submetido à ação da beta galactosidase, como alternativa para bebês intolerantes à lactose e não os privar de todos os outros benefícios oferecidos por esse alimento ideal.

First Trimester Dexamethasone Treatment Is Not Associated With Alteration in Resting-state Connectivity at Adolescent or Adult Age.

CONTEXT: Prenatal treatment with dexamethasone (DEX) has been used to prevent virilization in females at risk of congenital adrenal hyperplasia (CAH). Both affected and unaffected girls, as well boys, are treated until the genotype and sex of the fetus is known (gestational weeks 10-12). After that, only affected girls are treated until term. Exposure to a high synthetic glucocorticoid dosage may alter the developmental trajectory of the brain, with alterations in resting-state functional connectivity of the brain at adult age. OBJECTIVE: To investigate resting-state functional connectivity in subjects at risk of having CAH, exposed to DEX treatment during the first trimester of fetal life, both in the whole brain and in 3 regions of interest (amygdala, hippocampus, and superior frontal gyrus). DESIGN, SETTING, AND PARTICIPANTS: Eighteen participants (8 females) at risk of having CAH, exposed to DEX treatment, and 38 controls (24 females), age range 16 to 26 years, from a single research institute, underwent functional magnetic resonance imaging of the brain during rest. We used 2 different approaches: an exploratory whole-brain analysis and seed-based analysis. For seed-based analysis, we chose 3 different brain regions (amygdala, hippocampus, and superior frontal gyrus) based on our previous findings and literature evidence. RESULTS: We did not observe any differences in functional connectivity during rest, either in the whole brain nor in seed-based connectivity analyses at this adolescent and young adult age. CONCLUSIONS: Our results are reassuring; however, future studies on larger samples and with more sensitive methodologies are needed to confirm these findings.

Changes in resting-state functional connectivity in patients with congenital adrenal hyperplasia.

CONTEXT: Patients with congenital adrenal hyperplasia (CAH) are treated with life-long glucocorticoid (GC) replacement therapy. Negative effects on cognition, brain structure and function during working memory tasks have been identified. To date, no studies on functional connectivity during rest have been performed in patients with CAH. OBJECTIVE: To investigate resting-state functional connectivity in patients with CAH compared with healthy untreated controls and the association between functional connectivity in the precuneus and disease severity, dose of GC and working memory (WM). DESIGN, SETTING AND PARTICIPANTS: Thirty-one patients with CAH (18 females) and 38 healthy controls (24 females), aged 16-33 years, from a single research institute, underwent functional magnetic resonance imaging of the brain during rest. RESULTS: Patients with CAH showed increased functional connectivity in the precuneus compared with controls. Post-hoc tests within the precuneus showed that only patients with simple virilising CAH had stronger connectivity compared to controls. Further, while both patients with salt-wasting and simple virilising CAH performed worse on a WM task compared to controls, functional connectivity in the precuneus was not associated with executive function performance. CONCLUSION: Patients with CAH demonstrated altered functional connectivity during rest in the precuneus. Such a change may reflect a functional reorganisation in response to the CAH disease. The change in functional connectivity may depend on the severity of CAH.

Práctica de la lactancia materna y factores asociados entre mujeres jóvenes y adultas en el Municipio de Envigado, Antioquia-Colombia / Breastfeeding practices and associated factors among young and adult women in the Municipality of Envigado, Antioquia-Colombia

Introducción. La lactancia materna (LM) tiene retosdesde la preparación, nacimiento, primera hora de vida(PHV), protección de madres en hospital, apoyo de asesoras y familiares. La LM exclusiva en Colombia es 36,1% (1 mes)y en municipio Envigado alcanzó 3,1 meses, en 2015. Objetivo. Comparar la práctica de LM y factores asociadosa planificación de gestación, inicio, tipo y duración total de LMen madres jóvenes (MJ) y adultas (MA) del Municipio deEnvigado, Departamento Antioquia, Colombia. Material y métodos: Estudio cuantitativo, observacional,con muestreo probabilístico. De un universo de 3540 nacidos,se seleccionó 288 madres lactantes. Variables asociadas aservicios de salud, prácticas y tiempos de LM fueron estudia-das. Para análisis de datos se utilizó SPSSv22. Estudio apro-bado por comité de ética de la Universidad CES. Resultados: La entrega del bebé a la madre inmediata oPHV (83%), favorece la LM precoz (74%). La LM exclusiva(4,6 meses) y la total (12,6 meses) fueron similares en MJ(<27 años) y MA (≥27 años). En MJ tener al bebé hospitali-zado (p=0,00), el número de hijos (p=0,04) y un embarazoplanificado (p=0,02) predicen la LM en PHV, exclusiva y total En MA, tener al menor hospitalizado (p=0,01), la ocupación ylas asesorías predicen la LM en PHV, exclusiva y total. El prin-cipal predictor de LM exclusiva (p=0,02) y total (p=0,01) esla asesoría en LM. Discusión: La asesoría en LM es la principal estrategia deapoyo, promoción y mantenimiento de la LM, lo que se reflejaen las elevadas prevalencias de esta práctica esencial. Conclusiones: La asesoría en LM desde la gestación es elprincipal factor que predice la práctica de la LM exclusiva y to-tal. La hospitalización del neonato en periodo postparto y tipo de parto influyen significativamente en el contacto piela piel y la LM en PHV del bebé.(AU)

Introduction: Breastfeeding (BF) has challenges frompreparation, birth, first hour of life (FHL), protection of moth-ers in hospital, support from counselors and relatives.Exclusive BF in Colombia is 36.1% (1 month) and in Envigadomunicipality reached 3.1 months, in 2015. Objective: Compare the practice of BF and factors associ-ated with planning of gestation, onset, type and total durationof BF in young mothers (YW) and adults (AW) of theMunicipality of Envigado, Antioquia Department, Colombia. Material and methods: Quantitative, observational study,with probability sampling. From a universe of 3,540 new-borns, 288 lactating mothers were selected. Variables associ-ated with health services, practices and times of BF werestudied. SPSSv22 was used for data analysis. Study approvedby the ethics committee of the CES University. Results: Delivery of the baby to the immediate mother orFHL (83%), favors early BF (74%). Exclusive BF (4.6 months)and total BF (12.6 months) were similar in YW (<27 years)and AW (≥27 years). In YW, having the baby hospitalized (p= 0.00), the number of children (p = 0.04) and a plannedpregnancy (p = 0.02) predict BF in FHL, exclusive and totalBF. In AW, having the minor hospitalized (p = 0.01), occupa-tion and counseling predict BF in FHL, exclusive and total. Themain predictor of exclusive (p = 0.02) and total (p = 0.01) BFis BF counseling. Discussion. BF counseling is the main strategy for thesupport, promotion and maintenance of BF, which is reflectedin the high prevalences of this essential practice. Conclusions: Advice on BF from pregnancy is the mainfactor that predicts the practice of exclusive and total BF. Thehospitalization of the neonate in the postpartum period andtype of delivery significantly influences skin-to-skin contactand BF in the first hour of life.(AU)

Discrete white matter abnormalities at age 8-11 years in children born extremely preterm are not associated with adverse cognitive or motor outcomes.

AIM: Little is known about the prevalence of discrete white matter abnormalities (WMA) beyond the first years in children born extremely preterm (EPT) and the relation to neurodevelopmental outcomes. Our aim was to investigate the prevalence of discrete WMA in children born EPT and the relationship to neonatal white matter injuries (WMI), white matter (WM) volume, WM diffusivity and neurodevelopment. METHODS: The study was a part of a longitudinal follow-up study of EPT neonates. All children were scanned at Karolinska University hospital 2004-2007 (neonates) and 2014-2015 (children at 8-11 years). WMA was qualitatively assessed by visual inspection. Developmental assessment was conducted at 12 years. RESULTS: In total, 112 children (median age 10.3 years, 56 girls) underwent MRI of the brain (68 EPT, 45 controls). In the EPT group, a subset had MRI around term equivalent age (n = 61). In the EPT group, the prevalence of discrete WMA at 8-11 years was 52%. There was a positive association between WMI at TEA and 8-11 years. There was no association between WMI and WM volumes or diffusivity at 8-11 years. Discrete WMA was not related to neurodevelopmental outcomes. CONCLUSION: Discrete WMA was prevalent in children born EPT at 8-11 years but were not related to neurodevelopmental outcomes.

Exploring the distribution of grey and white matter brain volumes in extremely preterm children, using magnetic resonance imaging at term age and at 10 years of age.

OBJECTIVES: To investigate differences in brain volumes between children born extremely preterm and term born controls at term age and at 10 years of age. STUDY DESIGN: Children born extremely preterm (EPT), up to 26 weeks and 6 days gestational age, in Stockholm between January 1 2004 to March 31 2007 were included in this population-based cohort study. A total of 45 EPT infants were included at term age and 51 EPT children were included at 10 years of age. There were 27 EPT children included at both time points. Two different control groups were recruited; 15 control infants were included at term age and 38 control children at 10 years of age. The primary outcomes were the grey and white matter volumes. Linear regression, adjusted for intracranial volume and sex, was used. RESULTS: At term age, the extremely preterm infants had significantly smaller grey matter volume compared to the control infants with an adjusted mean difference of 5.0 cm3 and a 95% confidence interval of -8.4 to -1.5 (p = 0.004). At 10 years of age the extremely preterm children had significantly smaller white matter volume compared to the control children with an adjusted mean difference of 6.0 cm3 and a 95% confidence interval of -10.9 to -1.0 (p = 0.010). CONCLUSION: Extremely preterm birth was associated with reduced grey matter volume at term age and reduced white matter volume at 10 years of age compared to term born controls.

First Trimester DEX Treatment Is Not Associated with Altered Brain Activity During Working Memory Performance in Adults.

CONTEXT: Prenatal dexamethasone (DEX) treatment is sometimes used in pregnancies at risk for congenital adrenal hyperplasia (CAH) to prevent virilization in female fetuses with CAH. In boys and in fetuses not having CAH, there is no benefit of early DEX treatment and the risks of this therapy must be thoroughly investigated. High doses of prenatal glucocorticoid might alter the developmental trajectory of the brain into adulthood, even for CAH unaffected subjects treated with DEX for a short term during the first trimester. OBJECTIVE: The present study investigated brain activation during working memory performance in DEX-treated subjects compared with controls. DESIGN, SETTING, AND PARTICIPANTS: We tested 18 participants who were exposed to DEX during the first trimester of fetal life but did not have CAH (8 females; mean age 20.78 [standard deviation (SD), 2.67] years) and 40 control participants (24 females; mean age 20.53 [SD, 2.64]) from a single research institute. Participants underwent functional magnetic resonance imaging on a 3T scanner during a verbal and visuospatial working memory task. RESULTS: We did not observe any differences in brain activity during working memory performance. However, DEX-treated subjects responded faster during the experimental condition of the verbal WM task. CONCLUSIONS: First trimester DEX treatment did not seem to result in altered working memory-related brain activity at adult age. Our findings contribute to the risk-benefit assessment of prenatal DEX treatment in the context of CAH.

First-Trimester Prenatal Dexamethasone Treatment Is Associated With Alterations in Brain Structure at Adult Age.

CONTEXT: Prenatal treatment of human disease is rare. Dexamethasone (DEX) is used in pregnancies at risk for congenital adrenal hyperplasia (CAH) to prevent virilization in an affected female fetus. The safety and long-term consequences of prenatal DEX exposure on the brain are largely unknown. OBJECTIVE: We investigate whether first-trimester prenatal DEX treatment is associated with alterations in brain structure at adult age, and if these alterations are associated with DNA methylation, mood, and cognitive abilities. DESIGN, SETTING, AND PARTICIPANTS: T1-weighted and diffusion-weighted imaging scans, from a single research institute, are compared between 19 (9 women) first-trimester DEX-treated individuals, at risk of CAH but not having CAH, and 43 (26 women) controls (age range, 16.0-26.4 years). RESULTS: DEX-treated participants showed bilateral enlargement of the amygdala, increased surface area and volume of the left superior frontal gyrus, and widespread increased radial, mean, and axial diffusivity of white matter, in particular in the superior longitudinal fasciculi and corticospinal tracts. In the DEX-treated group, increased mean and radial diffusivity correlated with increased methylation of the promotor region of the FKBP5 gene. There were no group differences in cognition or in scales assessing depression or anxiety, and the relationship between brain structure and cognition did not differ between DEX-treated and controls. CONCLUSIONS: First-trimester prenatal DEX treatment is associated with structural alterations of the brain at adult age, with an accompanying change in gene methylation. The findings add to the safety concerns of prenatal DEX treatment in the context of CAH.

Making of the mind.

The essence of the mind is consciousness. It emerged early during evolution and ontogeny appears to follow the same process as phylogeny. Consciousness comes from multiple sources, including visual, auditory, sensorimotor and proprioceptive senses. These gradually combine during development to build a unified consciousness, due to the constant interactions between the brain, body, and environment. In the human the emergence of consciousness depends on the activation of the cortex by thalamocortical connections around 24 weeks after conception. Then, the human foetus can be potentially conscious, as it is aware of its body and reacts to touch, smell and sound and shows social expressions in response to external stimuli. However, it is mainly asleep and probably not aware of itself and its environment. In contrast, the newborn infant is awake after its first breaths of air and can be aware of its own self and others, express emotions and share feelings. The development of consciousness is a progressive, stepwise, structural and functional evolution of multiple intricate components. The infant fulfils some of the more basic criteria for consciousness. However, there are some important missing pieces at this stage, as it cannot remember the past and anticipate the future.

Breakdown of Whole-brain Dynamics in Preterm-born Children.

The brain operates at a critical point that is balanced between order and disorder. Even during rest, unstable periods of random behavior are interspersed with stable periods of balanced activity patterns that support optimal information processing. Being born preterm may cause deviations from this normal pattern of development. We compared 33 extremely preterm (EPT) children born at < 27 weeks of gestation and 28 full-term controls. Two approaches were adopted in both groups, when they were 10 years of age, using structural and functional brain magnetic resonance imaging data. The first was using a novel intrinsic ignition analysis to study the ability of the areas of the brain to propagate neural activity. The second was a whole-brain Hopf model, to define the level of stability, desynchronization, or criticality of the brain. EPT-born children exhibited fewer intrinsic ignition events than controls; nodes were related to less sophisticated aspects of cognitive control, and there was a different hierarchy pattern in the propagation of information and suboptimal synchronicity and criticality. The largest differences were found in brain nodes belonging to the rich-club architecture. These results provide important insights into the neural substrates underlying brain reorganization and neurodevelopmental impairments related to prematurity.

Altered Gray Matter Structure and White Matter Microstructure in Patients with Congenital Adrenal Hyperplasia: Relevance for Working Memory Performance.

Congenital adrenal hyperplasia (CAH) has been associated with brain structure alterations, but systematic studies are lacking. We explore brain morphology in 37 (21 female) CAH patients and 43 (26 female) healthy controls, aged 16-33 years, using structural magnetic resonance imaging to estimate cortical thickness, surface area, volume, subcortical volumes, and white matter (WM) microstructure. We also report data on a small cohort of patients (n = 8) with CAH, who received prenatal dexamethasone (DEX). Patients with CAH had reduced whole brain volume (4.23%) and altered structure of the prefrontal, parietal, and superior occipital cortex. Patients had reduced mean FA, and reduced RD and MD, but not after correcting for brain volume. The observed regions are hubs of the visuospatial working memory and default mode (DMN) networks. Thickness of the left superior parietal and middle frontal gyri was associated with visuospatial working memory performance, and patients with CAH performed worse on this task. Prenatal treatment with DEX affected brain structures in the parietal and occipital cortex, but studies in larger cohorts are needed. In conclusion, our study suggests that CAH is associated with brain structure alterations, especially in the working memory network, which might underlie the cognitive outcome observed in patients.

Beyond the Epileptic Focus: Functional Epileptic Networks in Focal Epilepsy.

Focal epilepsy can be conceptualized as a network disorder, and the functional epileptic network can be described as a complex system of multiple brain areas that interact dynamically to generate epileptic activity. However, we still do not fully understand the functional architecture of epileptic networks. We studied a cohort of 21 patients with extratemporal focal epilepsy. We used independent component analysis of functional magnetic resonance imaging (fMRI) data. In order to identify the epilepsy-related components, we examined the general linear model-derived electroencephalography-fMRI (EEG-fMRI) time courses associated with interictal epileptic activity as intrinsic hemodynamic epileptic biomarkers. Independent component analysis revealed components related to the epileptic time courses in all 21 patients. Each epilepsy-related component described a network of spatially distributed brain areas that corresponded to the specific epileptic network in each patient. We also provided evidence for the interaction between the epileptic activity generated at the epileptic network and the physiological resting state networks. Our findings suggest that independent component analysis, guided by EEG-fMRI epileptic time courses, have the potential to define the functional architecture of the epileptic network in a noninvasive way. These data could be useful in planning invasive EEG electrode placement, guiding surgical resections, and more effective therapeutic interventions.

Reduced structural brain asymmetry during neonatal life is potentially related to autism spectrum disorders in children born extremely preterm.

Disruption of the normal patterns of structural brain asymmetry, and in language-related areas, has been reported in individuals with autism spectrum disorder (ASD). We tested the hypothesis that 16 children born extremely preterm (EPT), and diagnosed with ASD at 6.5 years of age (EPT-ASD), would have different patterns of brain structural asymmetry, particularly in language-related areas, to 21 EPT children without ASD and 15 term-born children. They all underwent neonatal magnetic resonance imaging scans at 40 weeks of gestation. ASD diagnoses and the Weschler Intelligence Scale for Children-Fourth Edition, were performed in the EPT children, but not in the term group. Asymmetry indices (AIs) were assessed at three levels: global (hemispheres), lobar (brain lobes), and modular (primary sensorimotor, unimodal, and higher-order association areas). AIs were also assessed in language-related regions and correlational analyses were performed between these AIs and verbal scores. The EPT-ASD group showed reduced structural asymmetry at the modular level, mainly involving the higher-order association cortices and the language-related areas. Predominant positive correlations between language functioning and leftward AIs in the inferior frontal gyrus (opercular) and supplementary cortices, and rightward asymmetry in the angular and supramarginal gyri, were identified in the EPT-ASD group. The overall results suggest that reduced brain structural asymmetry identified during the neonatal period would be a risk factor for the development of ASD in EPT infants. This finding could identify EPT children at risk at an early stage, so that tailored interventions could be used to optimize their functions and quality of life. Autism Res 2019, 12: 1334-1343. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Babies born before the expected date (preterm) are more likely to develop autism, due to abnormal brain development. Compared with children without autism, preterm children with autism did not display the important physical differences between the two sides of their brain that are needed for normal functioning. As this alteration was found just after birth, this information could be used to identify children who are likely to develop autism, so that they can get medical support at an earlier age.

Visual-motor integration and fine motor skills at 6½ years of age and associations with neonatal brain volumes in children born extremely preterm in Sweden: a population-based cohort study.

OBJECTIVES: This exploratory study aimed to investigate associations between neonatal brain volumes and visual-motor integration (VMI) and fine motor skills in children born extremely preterm (EPT) when they reached 6½ years of age. SETTING: Prospective population-based cohort study in Stockholm, Sweden, during 3 years. PARTICIPANTS: All children born before gestational age, 27 weeks, during 2004-2007 in Stockholm, without major morbidities and impairments, and who underwent MRI at term-equivalent age. MAIN OUTCOME MEASURES: Brain volumes were calculated using morphometric analyses in regions known to be involved in VMI and fine motor functions. VMI was assessed with The Beery-Buktenica Developmental Test of Visual-Motor Integration-sixth edition and fine motor skills were assessed with the manual dexterity subtest from the Movement Assessment Battery for Children-second edition, at 6½ years. Associations between the brain volumes and VMI and fine motor skills were evaluated using partial correlation, adjusted for total cerebral parenchyma and sex. RESULTS: Out of 107 children born at gestational age <27 weeks, 83 were assessed at 6½ years and 66/83 were without major brain lesions or cerebral palsy and included in the analyses. A representative subsample underwent morphometric analyses: automatic segmentation (n=34) and atlas-based segmentation (n=26). The precentral gyrus was associated with both VMI (r=0.54, P=0.007) and fine motor skills (r=0.54, P=0.01). Associations were also seen between fine motor skills and the volume of the cerebellum (r=0.42, P=0.02), brainstem (r=0.47, P=0.008) and grey matter (r=-0.38, P=0.04). CONCLUSIONS: Neonatal brain volumes in areas known to be involved in VMI and fine motor skills were associated with scores for these two functions when children born EPT without major brain lesions or cerebral palsy were evaluated at 6½ years of age. Establishing clear associations between early brain volume alterations and later VMI and/or fine motor skills could make early interventions possible.