Search

A balanced excitation-inhibition ratio (E/I ratio) is critical for healthy brain function. Normative development of cortex-wide E/I ratio remains unknown. Here, we noninvasively estimate a putative marker of whole-cortex E/I ratio by fitting a large-scale biophysically plausible circuit model to resting-state functional MRI (fMRI) data. We first confirm that our model generates realistic brain dynamics in the Human Connectome Project. Next, we show that the estimated E/I ratio marker is sensitive to the gamma-aminobutyric acid (GABA) agonist benzodiazepine alprazolam during fMRI. Alprazolam-induced E/I changes are spatially consistent with positron emission tomography measurement of benzodiazepine receptor density. We then investigate the relationship between the E/I ratio marker and neurodevelopment. We find that the E/I ratio marker declines heterogeneously across the cerebral cortex during youth, with the greatest reduction occurring in sensorimotor systems relative to association systems. Importantly, among children with the same chronological age, a lower E/I ratio marker (especially in the association cortex) is linked to better cognitive performance. This result is replicated across North American (8.2 to 23.0 y old) and Asian (7.2 to 7.9 y old) cohorts, suggesting that a more mature E/I ratio indexes improved cognition during normative development. Overall, our findings open the door to studying how disrupted E/I trajectories may lead to cognitive dysfunction in psychopathology that emerges during youth., Competing Interests: Competing interests statement:The authors declare no competing interest.

Early life adversity has been posited to influence the pace of structural neurodevelopment. Most research, however, has relied on cross-sectional data, which do not reveal whether the pace of neurodevelopmental change is accelerated or slowed following early exposures. In a birth cohort study that included neuroimaging data obtained at 4.5, 6, and 7.5 years of age (N = 784), we examined associations among a cumulative measure of perinatal adversity relative to resources, nonlinear trajectories of hippocampal and amygdala volume, and children's subsequent depressive symptoms at 8.5 years of age. Greater adversity was associated with reduced bilateral hippocampal body volume in early childhood, but also to faster growth in the right hippocampal body across childhood. Further, the association between adversity and childhood depressive symptoms was mediated by faster hippocampal body growth. These findings suggest that perinatal adversity is biologically embedded in hippocampal structure development, including an accelerated pace of change in the right hippocampal body that is implicated in children's psychopathology risk. In addition, our findings suggest that reduced hippocampal volume is not inconsistent with accelerated hippocampal change; these aspects of structural development may typically co-occur, as smaller regional volumes in early childhood were associated with faster growth across childhood., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Metabolic syndrome score in children assesses the risk of developing cardiovascular disease in future. We aim to probe the role of the caudate in relation to the metabolic syndrome score. Furthermore, using both functional and structural neuroimaging, we aim to examine the interplay between functional and structural measures., Methods: A longitudinal birth cohort study with functional and structural neuroimaging data obtained at 4.5, 6.0 and 7.5 years and metabolic syndrome scores at 8.0 years was used. Pearson correlation and linear regression was used to test for correlation fractional anisotropy (FA) and fractional amplitude of low frequency fluctuations (fALFF) of the caudate with metabolic syndrome scores. Mediation analysis was used to test if later brain measures mediated the relation between earlier brain measures and metabolic syndrome scores. Inhibitory control was also tested as a mediator of the relation between caudate brain measures and metabolic syndrome scores., Results: FA at 4.5 years and fALFF at 7.5 years of the left caudate was significantly correlated with metabolic syndrome scores. Post-hoc mediation analysis showed that fALFF at 7.5 years fully mediated the relation between FA at 4.5 years and metabolic syndrome scores. Inhibitory control was significantly correlated with fALFF at 7.5 years, but did not mediate the relation between fALFF at 7.5 years and metabolic syndrome scores., Conclusions: We found that variations in caudate microstructure at 4.5 years predict later variation in functional activity at 7.5 years. This later variation in functional activity fully mediates the relation between microstructural changes in early childhood and metabolic syndrome scores at 8.0 years., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yap-Seng Chong is part of an academic consortium that has received research funding from Abbott Nutrition, Nestec, and Danone. All other authors report no financial relationships with commercial interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Early differences in reward behavior have been linked to executive functioning development. The nucleus accumbens (NAc) and orbitofrontal cortex (OFC) are activated by reward-related tasks and identified as key nodes of the brain circuit that underlie reward processing. We aimed to investigate the relation between NAc-OFC structural and functional connectivity in preschool children, as well as associations with future reward sensitivity and executive function. We showed that NAc-OFC structural and functional connectivity were not significantly associated in preschool children, but both independently predicted sensitivity to reward in males in a left-lateralized manner. Moreover, significant NAc-OFC structure-function coupling was only found in individuals who performed poorly on executive function tasks in later childhood, but not in the middle- and high-performing groups. As structure-function coupling is proposed to measure functional specialization, this finding suggests premature functional specialization within the reward network, which may impede dynamic communication with other regions, affects executive function development. Our study also highlights the utility of multimodal imaging data integration when studying the effects of reward network functional flexibility in the preschool age, a critical period in brain and executive function development., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The developing brain grows exponentially in the first few years of life. There is a need to have age-appropriate brain atlases that coherently characterize the geometry of the cerebral cortex, white matter tracts, and functional organization. This study employed multi-modal brain images of an Asian cohort and constructed brain structural and functional atlases for 6-month-old infants, 4.5-, 6-, and 7.5-year-old children. We exploited large deformation diffeomorphic metric mapping and probabilistic atlas generation approaches to integrate structural MRI and diffusion weighted images (DWIs) and to create the atlas where white matter tracts well fit into the cortical folding pattern. Based on this structural atlas, we then employed spectral clustering to parcellate the brain into functional networks from resting-state fMRI (rs-fMRI). Our results provided the atlas that characterizes the cortical folding geometry, subcortical regions, deep white matter tracts, as well as functional networks in a stereotaxic coordinate space for the four different age groups. The functional networks consisting of the primary cortex were well established in infancy and remained stable to childhood, while specific higher-order functional networks showed specific patterns of hemispherical, subcortical-cerebellar, and cortical-cortical integration and segregation from infancy to childhood. Our multi-modal fusion analysis demonstrated the use of the integrated structural and functional atlas for understanding coherent patterns of brain anatomical and functional development during childhood. Hence, our atlases can be potentially used to study coherent patterns of brain anatomical and functional development., (Copyright © 2021. Published by Elsevier Inc.)

Introduction: Fibrocartilaginous embolism and spinal cord infarction may resemble transverse myelitis with antecedent minor trauma (sporting activity or minor falls) or with hyperacute (<12-hour) presentation., Methods: Diagnostic criteria for fibrocartilaginous embolism and spinal cord infarction were applied to a 10-year (2007-2016) cohort of children aged 1 month to 16 years with transverse myelitis and clinical, laboratory, neuroimaging, and outcome data compared between those with and without antecedent minor trauma., Results: Thirty-two children of median age 8.9 (range 2.7-15.8) years were included; 19 (59%) were female. Falls at home, school, or play (6 children, 60%), swimming (2, 20%), physical education (1, 10%), and caning (1, 10%) were antecedent events in 10 (31%) children. Six (19%) had hyperacute presentations. One patient met spinal cord infarction criteria; none had fibrocartilaginous embolism. Children with transverse myelitis and antecedent minor trauma had single, short spinal cord lesions (median 3 vertebral bodies) but without a specific neuroimaging lesion pattern. None had intervertebral disc abnormalities or brain involvement and were negative for myelin oligodendrocyte and aquaporin 4 antibodies. Twenty-five (86%) of 29 had cerebrospinal fluid inflammation, and 30 (94%) received immunotherapy. Thirty (97%) were followed for a median of 3.6 (0.1-10.2) years, with good outcome (modified Rankin Scale score 0-1) in the majority (80%). Four (75%) with hyperacute presentation had a good outcome (modified Rankin Scale score 0-1), but the patient with spinal cord infarction was the most disabled (modified Rankin Scale score 4)., Conclusion: Minor trauma or hyperacute presentations does not always indicate fibrocartilaginous embolism or spinal cord infarction. Children with minor trauma preceding transverse myelitis have a distinct clinicoradiologic syndrome, with good outcome following immunotherapy.

Objective: Increased subcutaneous and visceral adipose tissue (SAT/VAT) volume is associated with risk for cardiometabolic diseases. This work aimed to develop and evaluate automated abdominal SAT/VAT segmentation on longitudinal MRI in adults with overweight/obesity using attention-based competitive dense (ACD) 3D U-Net and 3D nnU-Net with full field-of-view volumetric multi-contrast inputs., Materials and Methods: 920 adults with overweight/obesity were scanned twice at multiple 3 T MRI scanners and institutions. The first scan was divided into training/validation/testing sets (n = 646/92/182). The second scan from the subjects in the testing set was used to evaluate the generalizability for longitudinal analysis. Segmentation performance was assessed by measuring Dice scores (DICE-SAT, DICE-VAT), false negatives (FN), and false positives (FP). Volume agreement was assessed using the intraclass correlation coefficient (ICC)., Results: ACD 3D U-Net achieved rapid (< 4.8 s/subject) segmentation with high DICE-SAT (median ≥ 0.994) and DICE-VAT (median ≥ 0.976), small FN (median ≤ 0.7%), and FP (median ≤ 1.1%). 3D nnU-Net yielded rapid (< 2.5 s/subject) segmentation with similar DICE-SAT (median ≥ 0.992), DICE-VAT (median ≥ 0.979), FN (median ≤ 1.1%) and FP (median ≤ 1.2%). Both models yielded excellent agreement in SAT/VAT volume versus reference measurements (ICC > 0.997) in longitudinal analysis., Discussion: ACD 3D U-Net and 3D nnU-Net can be automated tools to quantify abdominal SAT/VAT volume rapidly, accurately, and longitudinally in adults with overweight/obesity., (© 2024. The Author(s).)

The diagnosis of central pontine hyperintensities on cranial magnetic resonance imaging has wide-spectrum clinical entities, and the pro-type diagnosis of these is central pontine myelinolysis. The rapid changes in extracellular environment due to an imbalance of electrolytes or metabolic or toxic stress to the myelin sheath can cause demyelination of white matter tracts in pons, which is why this situation could have different etiologies than just rapid sodium changes. Central pontine myelinolysis can be presented with different clinical scenarios from asymptomatic to death. Here, we present eight patients who had central pontine hyperintensities on radiological imaging but showed various clinical symptoms and different etiologies. The etiologies of these cases are hypertriglyceridemia, alcohol consumption, antidepressant usage, immunocompromised situations, uncontrolled diabetes mellitus, liver and kidney failure, electrolyte changes, and adrenal insufficiency. We aimed to take attention with this case series to the fact that not only fast correction of hyponatremia is the cause of central pontine myelinolysis, but also different etiologies could play a role in this situation, and making the central pontine myelinolysis diagnosis considering different diagnosis is very important. [ABSTRACT FROM AUTHOR]

Studies show robust links between disorganized attachment in infancy and socioemotional maladjustment in childhood. Little is known, however, about the links between disorganized attachment and brain development, and whether attachment-related differences in brain morphology translate into meaningful variations in child socioemotional functioning. This study examined the links between infants' disorganized attachment behaviors toward their mothers, whole-brain regional grey matter volume and thickness, and peer rejection in late childhood. Thirty-three children and their mothers took part in this study. The Strange Situation Procedure was used to assess mother–infant attachment when infants were 18 months old. Magnetic resonance imaging was performed when they were 10 years old to assess cortical thickness and grey matter volumes. Children and teachers reported on peer rejection 1 year later, as an indicator of socioemotional maladjustment. Results indicated that disorganized attachment was not associated with grey matter volumes. However, children who exhibited more disorganized attachment behaviors in infancy had significantly thicker cortices in bilateral middle and superior frontal gyri, and extending to the inferior frontal gyrus, as well as the orbitofrontal and insular cortices in the right hemisphere in late childhood. Moreover, children with thicker cortices in these regions experienced greater peer rejection, as rated by themselves and their teachers. Although preliminary, these results are the first to indicate that disorganized attachment may play a role in cortical thickness development and that changes in cortical thickness are associated with differences in child socioemotional functioning. [ABSTRACT FROM AUTHOR]

Background: There is increasing appreciation of the association of obesity beyond co-morbidities, such as cancers, Type 2 diabetes, hypertension, and stroke to also impact upon the muscle to give rise to sarcopenic obesity. Phenotypic knowledge of obesity is crucial for profiling and management of obesity, as different fat—subcutaneous adipose tissue depots (SAT) and visceral adipose tissue depots (VAT) have various degrees of influence on metabolic syndrome and morbidities. Manual segmentation is time consuming and laborious. Study focuses on the development of a deep learning-based, complete data processing pipeline for MRI-based fat analysis, for large cohort studies which include (1) data augmentation and preprocessing (2) model zoo (3) visualization dashboard, and (4) correction tool, for automated quantification of fat compartments SAT and VAT. Methods: Our sample comprised 190 healthy community-dwelling older adults from the Geri-LABS study with mean age of 67.85 ± 7.90 years, BMI 23.75 ± 3.65 kg/m2, 132 (69.5%) female, and mainly Chinese ethnicity. 3D-modified Dixon T1-weighted gradient-echo MR images were acquired. Residual global aggregation-based 3D U-Net (RGA-U-Net) and standard 3D U-Net were trained to segment SAT, VAT, superficial and deep subcutaneous adipose tissue depots (SSAT and DSAT). Manual segmentation from 26 subjects was used as ground truth during training. Data augmentations, random bias, noise and ghosting were carried out to increase the number of training datasets to 130. Segmentation accuracy was evaluated using Dice and Hausdorff metrics. Results: The accuracy of segmentation was SSAT:0.92, DSAT:0.88 and VAT:0.9. Average Hausdorff distance was less than 5 mm. Automated segmentation significantly correlated R2 > 0.99 (p < 0.001) with ground truth for all 3-fat compartments. Predicted volumes were within ± 1.96SD from Bland–Altman analysis. Conclusions: DL-based, comprehensive SSAT, DSAT, and VAT analysis tool showed high accuracy and reproducibility and provided a comprehensive fat compartment composition analysis and visualization in less than 10 s. [ABSTRACT FROM AUTHOR]

Summary: Background: Currently available infant body composition measurement methods are impractical for routine clinical use. The study developed anthropometric equations (AEs) to estimate fat mass (FM, kg) during the first year using air displacement plethysmography (PEA POD® Infant Body Composition System) and Infant quantitative magnetic resonance (Infant‐QMR) as criterion methods. Methods: Multi‐ethnic full‐term infants (n = 191) were measured at 3 days, 15 and 54 weeks. Sex, race/ethnicity, gestational age, age (days), weight‐kg (W), length‐cm (L), head circumferences‐cm (HC), skinfold thicknesses mm [triceps (TRI), thigh (THI), subscapular (SCP), and iliac (IL)], and FM by PEA POD® and Infant‐QMR were collected. Stepwise linear regression determined the model that best predicted FM. Results: Weight, length, head circumference, and skinfolds of triceps, thigh, and subscapular, but not iliac, significantly predicted FM throughout infancy in both the Infant‐QMR and PEA POD models. Sex had an interaction effect at 3 days and 15 weeks for both the models. The coefficient of determination [R2] and root mean square error were 0.87 (66 g) at 3 days, 0.92 (153 g) at 15 weeks, and 0.82 (278 g) at 54 weeks for the Infant‐QMR models; 0.77 (80 g) at 3 days and 0.82 (195 g) at 15 weeks for the PEA POD models respectively. Conclusions: Both PEA POD and Infant‐QMR derived models predict FM using skinfolds, weight, head circumference, and length with acceptable R2 and residual patterns. [ABSTRACT FROM AUTHOR]

In recent years, exploration of the developing brain has become a major focus for researchers and clinicians in an attempt to understand what allows children to acquire amazing and unique abilities, as well as the impact of early disruptions (eg, prematurity, neonatal insults) that can lead to a wide range of neurodevelopmental disorders. Noninvasive neuroimaging methods such as MRI are essential to establish links between the brain and behavioral changes in newborns and infants. In this review article, we aim to highlight recent and representative studies using the various techniques available: anatomical MRI, quantitative MRI (relaxometry, diffusion MRI), multiparametric approaches, and functional MRI. Today, protocols use 1.5 or 3T MRI scanners, and specialized methodologies have been put in place for data acquisition and processing to address the methodological challenges specific to this population, such as sensitivity to motion. MR sequences must be adapted to the brains of newborns and infants to obtain relevant good soft-tissue contrast, given the small size of the cerebral structures and the incomplete maturation of tissues. The use of age-specific image postprocessing tools is also essential, as signal and contrast differ from the adult brain. Appropriate methodologies then make it possible to explore multiple neurodevelopmental mechanisms in a precise way, and assess changes with age or differences between groups of subjects, particularly through large-scale projects. Although MRI measurements only indirectly reflect the complex series of dynamic processes observed throughout development at the molecular and cellular levels, this technique can provide information on brain morphology, structural connectivity, microstructural properties of gray and white matter, and on the functional architecture. Finally, MRI measures related to clinical, behavioral, and electrophysiological markers have a key role to play from a diagnostic and prognostic perspective in the implementation of early interventions to avoid long-term disabilities in children. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY STAGE: 1. [ABSTRACT FROM AUTHOR]

Age and sex differences in brain metabolite concentrations in early life are not well understood. We examined the associations of age and sex with brain metabolite levels in healthy neonates, and investigated the associations between neonatal brain metabolite concentrations and developmental outcomes. Forty-one infants (36–42 gestational weeks at birth; 39% female) of predominantly Hispanic/Latina mothers (mean 18 years of age) underwent MRI scanning approximately two weeks after birth. Multiplanar chemical shift imaging was used to obtain voxel-wise maps of N-acetylaspartate (NAA), creatine, and choline concentrations across the brain. The Bayley Scales of Infant and Toddler Development, a measure of cognitive, language, and motor skills, and mobile conjugate reinforcement paradigm, a measure of learning and memory, were administered at 4 months of age. Findings indicated that postmenstrual age correlated positively with NAA concentrations in multiple subcortical and white matter regions. Creatine and choline concentrations showed similar but less pronounced age related increases. Females compared with males had higher metabolite levels in white matter and subcortical gray matter. Neonatal NAA concentrations were positively associated with learning and negatively associated with memory at 4 months. Age-related increases in NAA, creatine, and choline suggest rapid development of neuronal viability, cellular energy metabolism, and cell membrane turnover, respectively, during early life. Females may undergo earlier and more rapid regional developmental increases in the density of viable neurons compared to males. [ABSTRACT FROM AUTHOR]

Congenital heart defects are the most common congenital anomalies, accounting for a third of all congenital anomaly cases. While surgical correction dramatically improved survival rates, the lag behind normal neurodevelopment appears to persist. Deficits in higher cognitive functions are particularly common, including developmental delay in communication and oral-motor apraxia. It remains unclear whether the varying degree of cognitive developmental delay is reflected in variability in brain growth patterns. To answer this question, we aimed to investigate whether the rate of regional brain growth is correlated with later life neurodevelopment. Forty-four newborns were included in our study, of whom 33 were diagnosed with dextro-transposition of the great arteries and 11 with other forms of severe congenital heart defects. During the first month of life, neonates underwent corrective or palliative cardiovascular bypass surgery, pre- and postoperative cerebral MRI were performed 18.7 ± 7.03 days apart. MRI was performed in natural sleep on a 3.0 T scanner using an 8-channel head coil, fast spin-echo T2-weighted anatomical sequences were acquired in three planes. Based on the principles of deformation-based morphometry, we calculated brain growth rate maps reflecting average daily growth occurring between pre- and postoperative brain images. An explorative, whole-brain, threshold-free cluster enhancement analysis revealed strong correlation between the growth rate of the Heschl's gyrus, anterior planum temporale and language score at 12 months of age, corrected for demographic variables (P = 0.018, t = 5.656). No significant correlation was found between brain growth rates and motor or cognitive scores. Post hoc analysis showed that the length of hospitalization interacted with this correlation, longer hospitalization resulted in faster enlargement of the internal CSF spaces. Our longitudinal cohort study provides evidence for the early importance of left-dominant perisylvian regions in auditory and language development before direct postnatal exposure to native language. In congenital heart disease patients, the perioperative period results in a critical variability of brain growth rate in this region, which is a reliable neural correlate of language development at 1 year of age. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to investigate the independent associations between age‐specific annual weight gain from birth to age 4 years and fat deposition in metabolically distinct compartments at age 4.5 years in a South Asian longitudinal birth cohort. Methods: Volumetric abdominal magnetic resonance imaging with comprehensive segmentation of deep and superficial subcutaneous adipose tissue (SAT) and visceral adipose tissues (VAT) was performed in 316 children (150 boys and 166 girls in three ethnic groups; 158 Chinese, 94 Malay, and 64 Indian) aged 4.5 years. Associations between fat volumes and annual relative weight gain conditional on past growth were assessed overall and stratified by sex and ethnicity. Results: Conditional relative weight gain had stronger associations with greater SAT and VAT at age 4.5 years in girls than boys and in Indians compared with Malay and Chinese. Overall, the magnitude of association was the largest during 2 to 3 years for SAT and 1 to 2 years for VAT. Despite similar body weight, Indian children and girls had the highest deep and superficial SAT volumes at age 4.5 years (all interactions P < 0.05). No significant sex or ethnic differences were observed in VAT. With increasing BMI, Indian children had the highest tendency to accumulate VAT, and girls accumulated more fat than boys in all depots (all interactions P < 0.001). Conclusions: Indian ethnicity and female sex predisposed children to accumulate more fat in the VAT depot with increasing conditional relative weight gain in the second year of life. Thus, 1 to 2 years of age may be a critical window for interventions to reduce visceral fat accumulation. [ABSTRACT FROM AUTHOR]

This paper is based on a literature review from 2011 to 2016. The paper is divided into two main sections. The first section relates to technical advances in fetal imaging techniques, including fetal motion compensation, imaging at 3.0 T, 3-D T2-weighted MRI, susceptibility-weighted imaging, computed tomography, morphometric analysis, diffusion tensor imaging, spectroscopy and fetal behavioral assessment. The second section relates to clinical updates, including cerebral lamination, migrational anomalies, midline anomalies, neural tube defects, posterior fossa anomalies, sulcation/gyration and hypoxic-ischemic insults. [ABSTRACT FROM AUTHOR]

Importance: Methamphetamine is a common illicit drug used worldwide. Methamphetamine and/or tobacco use by pregnant women remains prevalent. However, little is known about the effect of comorbid methamphetamine and tobacco use on human fetal brain development.Objective: To investigate whether microstructural brain abnormalities reported in children with prenatal methamphetamine and/or tobacco exposure are present at birth before childhood environmental influences.Design, Setting, and Participants: A prospective, longitudinal study was conducted between September 17, 2008, and February 28, 2015, at an ambulatory academic medical center. A total of 752 infant-mother dyads were screened and 139 of 195 qualified neonates were evaluated (36 methamphetamine/tobacco exposed, 32 tobacco exposed, and 71 unexposed controls). They were recruited consecutively from the community.Exposures: Prenatal methamphetamine and/or tobacco exposure.Main Outcomes and Measures: Quantitative neurologic examination and diffusion tensor imaging performed 1 to 3 times through age 4 months; diffusivities and fractional anisotropy (FA) assessed in 7 white matter tracts and 4 subcortical brain regions using an automated atlas-based method.Results: Of the 139 infants evaluated, 72 were female (51.8%); the mean (SE) postmenstrual age at baseline was 41.5 (0.27) weeks. Methamphetamine/tobacco-exposed infants showed delayed developmental trajectories on active muscle tone (group × age, P < .001) and total neurologic scores (group × age, P = .01) that normalized by ages 3 to 4 months. Only methamphetamine/tobacco-exposed boys had lower FA (group × age, P = .02) and higher diffusivities in superior (SCR) and posterior corona radiatae (PCR) (group × age × sex, P = .002; group × age × sex, P = .01) at baseline that normalized by age 3 months. Only methamphetamine/tobacco- and tobacco-exposed girls showed persistently lower FA in anterior corona radiata (ACR) (group, P = .04; group × age × sex, P = .01). Tobacco-exposed infants showed persistently lower axial diffusion in the thalamus and internal capsule across groups (P = .02).Conclusions and Relevance: Prenatal methamphetamine/tobacco exposure may lead to delays in motor development, with less coherent fibers and less myelination in SCR and PCR only in male infants, but these abnormalities may normalize by ages 3 to 4 months after cessation of stimulant exposure. In contrast, persistently less coherent ACR fibers were observed in methamphetamine/tobacco- and tobacco-exposed girls, possibly from increased dendritic branching or spine density due to epigenetic influences. Persistently lower diffusivity in the thalamus and internal capsule of all tobacco-exposed infants suggests aberrant axonal development. Collectively, prenatal methamphetamine and/or tobacco exposure may lead to delayed motor development and white matter maturation in sex- and regional-specific manners. [ABSTRACT FROM AUTHOR]

The human brain rapidly develops during the final weeks of gestation and in the first two years following birth. Diffusion tensor imaging (DTI) is a unique in vivo imaging technique that allows three-dimensional visualization of the white matter anatomy in the brain. It has been considered to be a valuable tool for studying brain development in early life. In this review, we first introduce the DTI technique. We then review DTI findings on white matter development at the fetal stage and in infancy as well as DTI applications for understanding neurocognitive development and brain abnormalities in preterm infants. Finally, we discuss limitations of DTI and potential valuable imaging techniques for studying white matter myelination. [ABSTRACT FROM AUTHOR]

Background: The dramatic emergence of noncommunicable diseases (NCD) in Asia, albeit with ethnic variation, has coincided with the rapid socioeconomic and nutritional transition taking place in the region, with the prevalence of diabetes rising 5-fold in Singapore in less than 4 decades. The Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort study recruited 1,247 expectant mothers of Chinese, Malay, or Indian ethnicity in their first trimester, with detailed longitudinal tracking - through the antenatal period, birth, and the child's first 4 years of life - to examine the potential roles of fetal, developmental, and epigenetic factors in early pathways to metabolic and neurodevelopmental outcomes. Key Messages: A number of findings with a translational and clinical focus have already emerged. In the mothers, we found that changes and differences in food consumption varied across ethnic groups, with persistence of traditional beliefs, during pregnancy and the postpartum period. During pregnancy, higher maternal glucose levels, even in the absence of gestational diabetes mellitus, had graded relations with infant adiposity. Relations between maternal emotional health and birth outcomes and neurodevelopment have been identified. Genotype (25%) and in particular gene × environment interactions (75%) shape interindividual variations in the DNA methylome at birth. The complex effects of fixed genetic variations and different in utero environments can influence the epigenetic status at birth and the later-life phenotype. Conclusions: The richness of the clinical data in 3 ethnicities, the extent of the biospecimen collection, and the extensive infancy and preschool follow-up have allowed us to study the biological pathways that link fetal development to health outcomes. In the coming years, more sophisticated analyses of epigenotype-phenotype relationships will become possible as the children grow and develop. Our studies will lead to the development of clinical and population-based interventions to reduce the burden of NCD. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Cui R, Fayek S, Rand EB, Feygin T, Khrichenko D, Shaked A. Central pontine myelinolysis: A case report and clinical-pathological review. Pediatr Transplantation 2011. © 2011 John Wiley & Sons A/S. Abstract: An 11-yr-old child presented with acute mental status changes and spastic quadriplegia after orthotopic liver transplantation. Magnetic resonance (MR) imaging findings were consistent with central pontine and EPM. Initial immunosuppression included tacrolimus, mycophenolate mofetil, and corticosteroids. Given that neurotoxicity is a well-established side effect of CNI, the patient was converted to rapamycin and subsequently experienced significant neurologic recovery. The temporal resolution of the patient's symptoms suggests that prompt recognition of central pontine and EPM and conversion from tacrolimus to rapamycin during the early post-operative course may have therapeutic benefits for patients undergoing pediatric transplant with CNI-related neurotoxicity. [ABSTRACT FROM AUTHOR]

The amygdala and hippocampus undergo rapid development in early life. The relative contribution of genetic and environmental factors to the establishment of their developmental trajectories has yet to be examined. We performed imaging on neonates and examined how the observed variation in volume and microstructure of the amygdala and hippocampus varied by genotype, and compared with prenatal maternal mental health and socioeconomic status. Gene × Environment models outcompeted models containing genotype or environment only to best explain the majority of measures but some, especially of the amygdaloid microstructure, were best explained by genotype only. Models including DNA methylation measured in the neonate umbilical cords outcompeted the Gene and Gene × Environment models for the majority of amygdaloid measures and minority of hippocampal measures. This study identified brain region‐specific gene networks associated with individual differences in fetal brain development. In particular, genetic and epigenetic variation within CUX1 was highlighted. [ABSTRACT FROM AUTHOR]