Neonatal Brain Development Research Articles

RanBP9 Plays a Critical Role in Neonatal Brain Development in Mice

RanBP9 is known to act as a scaffolding protein bringing together a variety of cell surface receptors and intracellular targets thereby regulating functions as diverse as neurite and axonal outgrowth, cell morphology, cell proliferation, myelination, gonad development, myofibrillogenesis and migration of neuronal precursors. Though RanBP9 is ubiquitously expressed in all tissues, brain is one of the organs with the highest expression levels of RanBP9. In the neurons, RanBP9 is localized mostly in the cytoplasm but also in the neurites and dendritic processes. We recently demonstrated that RanBP9 plays pathogenic role in Alzheimer’s disease. To understand the role of RanBP9 in the brain, here we generated RanBP9 null mice by gene-trap based strategy. Most of Ran−/− mice die neonatally due to defects in the brain growth and development. The major defects include smaller cortical plate (CP), robustly enlarged lateral ventricles (LV) and reduced volume of hippocampus (HI). The lethal phenotype is due to a suckling defect as evidenced by lack of milk in the stomachs even several hours after parturition. The complex somatosensory system which is required for a behavior such as suckling appears to be compromised in Ran−/− mice due to under developed CP. Most importantly, RanBP9 phenotype is similar to ERK1/2 double knockout and the neural cell adhesion receptor, L1CAM knockout mice. Both ERK1 and L1CAM interact with RanBP9. Thus, RanBP9 appears to control brain growth and development through signaling mechanisms involving ERK1 and L1CAM receptor.

Need for Improved Risk Communication of Fish Consumption Advisories to Protect Maternal and Child Health: Influence of Primary Informants

Fish consumption has established benefits, including the promotion of cardiovascular health and pre- and neonatal brain and eye development, but local freshwater fish may be a source of contaminants that are especially harmful to fetuses and young children, such as the neurotoxic and developmentally toxic methylmercury and polychlorinated biphenyls. Fish consumption advisories may be issued by state health departments to limit human exposure to these and other toxicants. This study examined the efficacy of a sign designed by the North Carolina Division of Public Health that was posted along a reservoir (Badin Lake) in central North Carolina, USA, for increasing anglers’ awareness of a fish consumption advisory, with a special focus on anglers who share their catch with women and children. In this study, 109 anglers were interviewed about their awareness of fish consumption advisories in general and their knowledge of the Badin Lake fish advisory in particular. Shore anglers were significantly less likely to be aware of the term “fish consumption advisory” and of the specific advisory for Badin Lake than boat anglers. Although a significant increase in knowledge of the specific fish consumption advisory was found for the entire sample of study participants after the sign intervention, a commensurate increase in knowledge was not found for a subsample of anglers who reported sharing their catch with women and children. Study findings underscore differences in fish consumption advisory awareness among subpopulations. Specifically, the study revealed the importance of characterizing the communication needs of shore anglers and anglers who share their catch with sensitive subpopulations (e.g., women and children) for the creation of more targeted communications of fish consumption advisories.

Acquisition Guidelines and Quality Assessment Tools for Analyzing Neonatal Diffusion Tensor MRI Data

Diffusion tensor imaging is a valuable measure in clinical settings to assess diagnosis and prognosis of neonatal brain development. However, obtaining reliable images is not straightforward because of the tissue characteristics of the neonatal brain and the high likelihood of motion artifacts. In this review, we present guidelines on how to acquire DTI data of the neonatal brain and recommend high-quality data acquisition and processing as an essential means to obtain accurate and robust parametric maps. Sudden head movements are problematic for DTI in neonates, and these may lead to incorrect values. We describe strategies to minimize the corrupting effects both in terms of acquisition (eg, more gradient directions) and postprocessing (eg, tensor estimation methods). In addition, tools are described that can help assess whether a dataset is of sufficient quality for further assessment.

An fMRI Compatible Wrist Robotic Interface to Study Brain Development in Neonates

A comprehensive understanding of the mechanisms that underlie brain development in premature infants and newborns is crucial for the identification of interventional therapies and rehabilitative strategies. fMRI has the potential to identify such mechanisms, but standard techniques used in adults cannot be implemented in infant studies in a straightforward manner. We have developed an MR safe wrist stimulating robot to systematically investigate the functional brain activity related to both spontaneous and induced wrist movements in premature babies using fMRI. We present the technical aspects of this development and the results of validation experiments. Using the device, the cortical activity associated with both active and passive finger movements were reliably identified in a healthy adult subject. In two preterm infants, passive wrist movements induced a well localized positive BOLD response in the contralateral somatosensory cortex. Furthermore, in a single preterm infant, spontaneous wrist movements were found to be associated with an adjacent cluster of activity, at the level of the infant's primary motor cortex. The described device will allow detailed and objective fMRI studies of somatosensory and motor system development during early human life and following neonatal brain injury.

Maternal long-chain PUFA supplementation during protein deficiency improves brain fatty acid accretion in rat pups by altering the milk fatty acid composition of the dam.

Long-chain PUFA (LC-PUFA) are important for fetal and neonatal brain development. However, their accretion in the brain is compromised during maternal protein restriction. Hence, we investigated the effect of maternal supplementation with n-3 DHA plus n-6 arachidonic acid (ARA) at a low protein level (9%) on offspring brain fatty acid accretion using Wistar rats (nine rats per group) randomly fed a control (C), a low-protein (LP) or a low-protein DHA+ARA-supplemented (LPS) diet during gestation and lactation. At birth, pups from the LPS group had the highest brain DHA and n-3 fatty acid levels (P=0·001), whereas pups from the LP group had the highest MUFA (P=0·05) but the lowest DHA and total n-3 PUFA levels (P=0·000). During lactation, pups from the LPS group accrued significantly more α-linolenic acid (P=0·003), EPA (P=0·02) and DHA (P=0·000) in brain lipids than pups from the LP group, whereas brain lipids of pups from the LP group had markedly increased levels of the n-3 deficiency marker docosapentaenoic acid and n-6:n-3 ratio (P=0·000). Owing to supplementation, milk from LPS dams had the highest DHA and ARA, but lower SCFA and medium-chain fatty acids as compared with milk from C and LP dams during early lactation, but normalised by mid-lactation. To conclude, adverse effects of restricted maternal protein intake on LC-PUFA accretion in the brain of offspring were ameliorated by alterations in maternal milk fatty acid profile due to supplementation. Results underscore the importance of LC-PUFA for protein-deficient mothers during gestation as well as lactation to achieve the optimum brain LC-PUFA status of progeny.

Regional changes in brain perfusion during brain maturation measured non-invasively with Arterial Spin Labeling MRI in neonates

PurposeThe purpose of this study was to evaluate if non-invasive Arterial Spin Labeling MR imaging can be used to assess changes in brain perfusion with age which reflect neonatal brain development. For this purpose regional perfusion values obtained with ASL MR imaging were evaluated as a function of postmenstrual age. Materials and methodsPulsed ASL imaging was performed in 33 neonates with a postmenstrual age from 30 to 53 weeks. Whole brain cerebral blood flow (wbCBF), CBF in the basal ganglia and thalamus (BGT-CBF), in the occipital cortex (OC-CBF) and the frontal cortex (FC-CBF) were measured. Regional CBF values were expressed quantitatively (in ml/100gmin) and relative as a percentage of the wbCBF. ResultsMean wbCBF increased significantly from 7±2ml/100gmin (mean±sd) at 31±2 weeks postmenstrual age to 12±3ml/100gmin at term-equivalent age (TEA) and 29±9ml/100gmin at 52±1 weeks postmenstrual age. Relative regional CBF was highest in the BGT at all time-points. Relative OC-and FC-CBF increased significantly from 31±2 weeks postmentrual age to TEA. A significant difference in relative BGT-CBF and OC-CBF was shown between infants at 31±2 weeks postmenstrual age and infants scanned at 52±1 weeks postmenstrual age. Relative perfusion in the BGT measured at TEA was significant different compared to 52±1 weeks postmenstrual age. ConclusionIn conclusion, regional differences in CBF and changes with postmenstrual age could be detected with ASL in neonates. This suggests that ASL can be used as a non-invasive tool to investigate brain maturation in neonates.

Aluminum overload increases oxidative stress in four functional brain areas of neonatal rats

BackgroundHigher aluminum (Al) content in infant formula and its effects on neonatal brain development are a cause for concern. This study aimed to evaluate the distribution and concentration of Al in neonatal rat brain following Al treatment, and oxidative stress in brain tissues induced by Al overload.MethodsPostnatal day 3 (PND 3) rat pups (n =46) received intraperitoneal injection of aluminum chloride (AlCl3), at dosages of 0, 7, and 35 mg/kg body wt (control, low Al (LA), and high Al (HA), respectively), over 14 d.ResultsAluminum concentrations were significantly higher in the hippocampus (751.0 ± 225.8 ng/g v.s. 294.9 ± 180.8 ng/g; p < 0.05), diencephalon (79.6 ± 20.7 ng/g v.s. 20.4 ± 9.6 ng/g; p < 0.05), and cerebellum (144.8 ± 36.2 ng/g v.s. 83.1 ± 15.2 ng/g; p < 0.05) in the HA group compared to the control. The hippocampus, diencephalon, cerebellum, and brain stem of HA animals displayed significantly higher levels of lipid peroxidative products (TBARS) than the same regions in the controls. However, the average superoxide dismutase (SOD) activities in the cerebral cortex, hippocampus, cerebellum, and brain stem were lower in the HA group compared to the control. The HA animals demonstrated increased catalase activity in the diencephalon, and increased glutathione peroxidase (GPx) activity in the cerebral cortex, hippocampus, cerebellum, and brain stem, compared to controls.ConclusionAluminum overload increases oxidative stress (H2O2) in the hippocampus, diencephalon, cerebellum, and brain stem in neonatal rats.

Omega 3 fatty acids and inborn errors of metabolism

A number of studies are investigating the role of n-3 polyunsaturated fatty acids in children with metabolic inborn errors, while the effects on visual and brain development in premature infants and neonates are well known. However, their function incertain chronic neurological, inflammatory and metabolic disorders is still under study. Standards should be established to help identify the need of docosahexaenoic acid supplementation in conditions requiring a restricted diet resulting in an altered metabolism system, and find scientific evidence on the effects of such supplementation. This study reviews relevant published literature to propose adequate n-3 intake or supplementation doses for different ages and pathologies. The aim of this review is to examine the effects of long chain polyunsaturated fatty acids supplementation in preventing cognitive impairment or in retarding its progress, and to identify nutritional deficiencies, in children with inborn errors of metabolism. Trials were identified from a search of the Cochrane and MEDLINE databases in 2011. These databases include all major completed and ongoing double-blind, placebo-controlled, randomized trials, as well as all studies in which omega-3 supplementation was administered to children with inborn errors, and studies assessing omega-3 fatty acids status in plasma in these pathologies. Although few randomized controlled trials met the inclusion criteria of this review, some evidenced that most of children with inborn errors are deficient in omega-3 fatty acids, and demonstrated that supplementation might improve their neural function, or prevent the progression of neurological impairment. Nontheless, further investigations are needed on this issue.

Zinc in the central nervous system: From molecules to behavior.

The trace metal zinc is a biofactor that plays essential roles in the central nervous system across the lifespan from early neonatal brain development through the maintenance of brain function in adults. At the molecular level, zinc regulates gene expression through transcription factor activity and is responsible for the activity of dozens of key enzymes in neuronal metabolism. At the cellular level, zinc is a modulator of synaptic activity and neuronal plasticity in both development and adulthood. Given these key roles, it is not surprising that alterations in brain zinc status have been implicated in a wide array of neurological disorders including impaired brain development, neurodegenerative disorders such as Alzheimer's disease, and mood disorders including depression. Zinc has also been implicated in neuronal damage associated with traumatic brain injury, stroke, and seizure. Understanding the mechanisms that control brain zinc homeostasis is thus critical to the development of preventive and treatment strategies for these and other neurological disorders.

Association between neonatal iron overload and early human brain development in premature infants

BackgroundEmerging evidence suggests that excess iron may be detrimental for brain development. However, little is known regarding the association between neonatal iron overload and subsequent neurodevelopment during infancy in vulnerable premature infants. AimsTo evaluate the association between neonatal iron overload and neurodevelopment in premature infants. Study designProspective cohort study. Subjects24–32weeks gestational age infants who had serum ferritin (SF) measured at 34–35weeks post-menstrual age (PMA) and did not meet exclusion criteria: SF<76ng/ml, toxoplasmosis, syphilis, rubella, cytomegalovirus, herpes infections, chromosomal disorders, or craniofacial anomalies were eligible. In addition, infants with sepsis or elevated C-reactive protein within 10days before their SF measurement were excluded. Outcome measuresInfants were evaluated for neurodevelopmental outcome at 8–12months of age and were deemed to have neurodevelopmental impairment if they had one or more of the following: mental developmental index<70, abnormal neurological examination, bilateral blindness, bilateral deafness, or required occupational, physical, or speech therapy. Results95 infants were studied. 70 had normal iron status (SF 76–400ng/ml) while 25 were deemed to have iron overload (SF >400ng/ml) at 34–35weeks PMA. There was a marginal increase in neurodevelopmental impairment among infants with iron overload compared to infants with normal iron status (64% vs. 41%, p=0.05). However, after controlling for confounders, iron overload was not associated with neurodevelopmental impairment (Adjusted OR 0.71, 95% CI, 0.21–2.5). ConclusionModest neonatal iron overload is not associated with neurodevelopmental impairment during infancy in premature infants.

Impact of congenital heart disease on brain development in newborn infants

Objective:To assess brain development and brain injury in neonates with cyanotic and acyanotic congenital heart disease (CHD).Methods:The study included 52 term infants with CHD who were divided into two groups: Cyanotic (n=21) and acyanotic (n=31). Fifteen healthy neonates of matched age and sex were enrolled in the study as controls. Three-dimensional proton magnetic resonance spectroscopic imaging and diffusion tensor imaging were used to assess brain development and injury. We calculated the ratio of N-acetylaspartate (NAA) to choline (which increases with maturation), average diffusivity (which decreases with maturation), fractional anisotropy of white matter (which increases with maturation), and the ratio of lactate to choline (which increases with brain injury).Results:As compared with control neonates, those with CHD had significant decrease in NAA/choline ratio (P<0.001), significant increase in lactate/choline ratio (P<0.0001), significant increase in average diffusivity (P<0.0001), and significant decrease of white matter fractional anisotropy (P<0.001). Neonates with cyanotic CHD had significant less brain development and more brain injury than those with acyanotic CHD (P<0.05).Conclusions:Newborn infants with cyanotic and acyanotic CHD are at high risk of brain injury and impaired brain maturity.

Oxidative Stress in Fetal and Neonatal Brain Development

Free radicals (FRs) are normally generated as by-products of aerobic respiration and various metabolic processes. Oxidative stress (OS) occurs when the production of FRs exceeds the capacity of antioxidant defenses. Nevertheless, a certain amount of OS is required to allow for the normal progression of embryonic and fetal growth. OS has been implicated in the regulation of reproductive processes in both animal and human, such as follicular development, ovulation, fertilization, embryogenesis, placental differentiation and growth. In contrast OS has emerged as a likely promoter of several pregnancy-related disorders, such as spontaneous abortions, embryopathies, preeclampsia, fetal growth restriction, preterm labor and low birth weight. Clinical studies suggest a link between maternal and fetal infection/inflammation and brain damage. The most common view is that intrauterine infection causes a fetal systemic inflammatory response resulting in injury to cerebral white matter. At birth, newborn is exposed to a relatively hyperoxic environment and additional FRs sources such as inflammation, hypoxia, ischemia-reperfusion, glutamate and non protein bound iron (NPBI) release may enhance OS. The susceptibility of the developing brain in extreme low gestational age newborn is due to the intrinsic vascular derangements in the autoregulation of cerebral blood flow and the local metabolic vulnerability, furthermore asphyxia causes an increase in NPBI, that significantly correlates with neurodevelopmental outcome. As matter of fact, a positive correlation exists between the development of IVH and NPBI levels in cord blood suggesting the dangerous potential of NPBI on oligodendrocytes. Brain injury is a leading cause of mortality and disability. The improvement in understanding the pathophysiological mechanisms involved in perinatal brain lesions will allow to identify new neuroprotective strategies.

A Combined Manifold Learning Analysis of Shape and Appearance to Characterize Neonatal Brain Development

Large medical image datasets form a rich source of anatomical descriptions for research into pathology and clinical biomarkers. Many features may be extracted from data such as MR images to provide, through manifold learning methods, new representations of the population's anatomy. However, the ability of any individual feature to fully capture all aspects morphology is limited. We propose a framework for deriving a representation from multiple features or measures which can be chosen to suit the application and are processed using separate manifold-learning steps. The results are then combined to give a single set of embedding coordinates for the data. We illustrate the framework in a population study of neonatal brain MR images and show how consistent representations, correlating well with clinical data, are given by measures of shape and of appearance. These particular measures were chosen as the developing neonatal brain undergoes rapid changes in shape and MR appearance and were derived from extracted cortical surfaces, nonrigid deformations, and image similarities. Combined single embeddings show improved correlations demonstrating their benefit for further studies such as identifying patterns in the trajectories of brain development. The results also suggest a lasting effect of age at birth on brain morphology, coinciding with previous clinical studies.

Neonatal exposure to propofol affects BDNF but not CaMKII, GAP-43, synaptophysin and tau in the neonatal brain and causes an altered behavioural response to diazepam in the adult mouse brain

Animal studies have shown that neonatal anaesthesia is associated with acute signs of neurodegeneration and later behavioural changes in adult animals. The anaesthetic effect of propofol is thought to be mediated by γ-amino butyric acid (GABA) A receptors. The present study investigated the effects on proteins important for normal neonatal brain development (i.e. BDNF, CaMKII, GAP-43, synaptophysin and tau), and adult spontaneous motor and anxiety-like behaviours in response to diazepam, after neonatal exposure to propofol. Ten-day-old mice were exposed to 0, 10 or 60 mg/kg bodyweight propofol. Neonatal propofol exposure changed the levels of BDNF in the brain, 24 h after exposure, but did not alter any of the other proteins. Neonatal propofol exposure significantly changed the adult response to the GABA-mimetic drug diazepam, manifest as no change in spontaneous motor activity and/or reduced sedative effect and an extinguished effect on the reduction of anxiety-like behaviours in an elevated plus maze. Although no adult spontaneous behavioural changes were detected after neonatal propofol exposure, the exposure caused an adult dose-dependent decrease in the response to the GABA-mimetic drug diazepam. These changes may be due to neonatal alterations in BDNF levels.

Intrauterine inflammation, insufficient to induce parturition, still evokes fetal and neonatal brain injury

Exposure to prenatal inflammation is a known risk factor for long term neurobehavioral disorders including cerebral palsy, schizophrenia, and autism. Models of systemic inflammation during pregnancy have demonstrated an association with an immune response an adverse neurobehavioral outcomes for the exposed fetus. Yet, the most common route for an inflammatory exposure to a fetus is from intrauterine inflammation as occurs with chorioamnionitis. The aims of this study were to assess the effect of intrauterine inflammation on fetal and neonatal brain development and to determine if the gestational age of exposure altered the maternal or fetal response to inflammation. CD-1 timed pregnant mice on embryonic day 15 (E15) and E18.5 were utilized for this study. Dams were randomized to receive intrauterine infusion of lipopolysaccharide (LPS, 50 μg/dam) or normal saline. Different experimental groups were used to assess both acute and long-term outcomes. For each gestational age and each treatment group, fetal brains, amniotic fluid, maternal serum and placentas were collected 6 h after intrauterine infusion. Rates of preterm birth, maternal morbidity and litter size were assessed. IL6 levels were assayed in maternal serum and amniotic fluid. An immune response was determined in the fetal brains and placentas by QPCR. Cortical cultures were performed to assess for fetal neuronal injury. Gene expression changes in postnatal day 7 brains from exposed and unexposed pups were determined. In the preterm period, low dose LPS resulted in a 30% preterm birth rate. Litter sizes were not different between the groups at either gestational age. IL6 levels were not significantly increased in maternal serum at either gestational time period. Low dose LPS increased IL6 levels in the amniotic fluid from exposed dams in the term but not preterm period. Regardless of gestational age of exposure, low dose intrauterine LPS activated an immune response in the placenta and fetal brain. Exposure to intrauterine LPS significantly decreased dendritic counts in cortical cultures from both the preterm and term period. Exposure to intrauterine inflammation altered gene expression patterns in the postnatal brain; this effect was dependent on gestational age of exposure. In conclusion, intrauterine inflammation, even in the absence of preterm parturition, can evoke fetal brain injury as evidence by alterations in cytokine expression and neuronal injury. Despite an absent or limited maternal immune response in low dose intrauterine inflammation, the immune system in the placenta is activated which is likely sufficient to induce a fetal immune response and subsequent brain injury. Changes in the fetal brain lead to changes in gene expression patterns into the neonatal period. Subclinical intrauterine inflammation can lead to fetal brain injury and is likely to be mechanistically associated with long term adverse outcomes for exposed offspring.

Contributions of Diffusion-Weighted Imaging to Fetal and Neonatal Imaging

Diffusion-weighted imaging has contributed to our understanding of fetal and neonatal brain development. This article will review the role of diffusion-weighted imaging and diffusion tensor imaging in fetuses and neonates, focusing primarily on normal brain developmental processes and then on pathologic processes that can be characterized using diffusion tensor imaging.

Phase contrast imaging in neonates

Magnetic resonance phase images can yield superior gray and white matter contrast compared to conventional magnitude images. However, the underlying contrast mechanisms are not yet fully understood. Previous studies have been limited to high field acquisitions in adult volunteers and patients. In this study, phase imaging in the neonatal brain is demonstrated for the first time. Compared to adults, phase differences between gray and white matter are significantly reduced but not inverted in neonates with little myelination and iron deposits in their brains. The remaining phase difference between the neonatal and adult brains may be due to a different macromolecule concentration in the unmyelinated brain of the neonates and thus a different frequency due to water macromolecule exchange. Additionally, the susceptibility contrast from brain myelination can be separately studied in neonates during brain development. Therefore, magnetic resonance phase imaging is suggested as a novel tool to study neonatal brain development and pathologies in neonates.

Thyroidology and public health: The challenges ahead

Thyroidology and public health: The challenges ahead

Prenatal PBDEs and Neurodevelopment: Animal Studies and Human Health Assessment

Herbstman et al. (2010) reported an association between polybrominated diphenyl ether (PBDE) levels in cord blood and neurodevelopmental effects in the children at specific ages. As a basis for their work, the authors cited several animal studies that reported causal relationships between prenatal exposure to PBDEs and developmental neurotoxicity. We are concerned that Herbstman et al.’s research suffers from investigator bias based on the reasons that follow. First, the U.S. Environmental Protection Agency (EPA) cosponsored an expert panel that refuted the experimental design employed in most of the studies cited by Herbstman et al. (2010) as a basis for their work. The U.S. EPA expert panel concluded that the experimental design failed to control for litter effects (Holson et al. 2008). Next, the potential for specific brominated flame retardants to cause developmental neurotoxicity has been evaluated under Good Laboratory Practice (GLP) standards and according to validated test guidelines. In each case, the claims of developmental neurotoxicity from non-GLP, non-guideline studies were not reproducible (reviewed by Williams and DeSesso 2010). This is significant because in Europe, data generated from studies performed under GLP and according to validated test guidelines are considered the highest quality and most reliable (European Chemicals Agency 2008). Further, regulatory agencies in Europe and the United States seem to have shifted their stance on the non-GLP, non-guideline studies that have reported brominated flame retardant–induced developmental neurotoxicity. For example, when the European Union issued their Risk Assessment Report on hexabromocyclododecane (HBCD), a brominated flame retardant (European Chemicals Bureau 2008), they stated that … Eriksson et al. (2006) [i.e., the study reporting HBCD-induced developmental neurotoxicity] is not performed according to current guideline and GLP …. However, similar results on developmental neurotoxicity have been published for decabromodiphenylether by the same authors using the same method [e.g., Viberg et al. (2003), which was cited by Herbstman et al. (2010)]. For decabromodiphenylether it has been agreed to perform a new toxicokinetics/developmental neurotoxicity study according to a modified OECD guideline and GLP. The results from this new decabromodiphenylether study will serve as guidance on how to interpret the data from the Eriksson study, and may also serve as a basis on how to proceed with further testing of neurotoxicity. For two of the studies cited by Herbstman et al. (2010), which were used by the U.S. EPA for deriving reference doses for PBDEs 153 and 209 (U.S. EPA 2008a, 2008b), the U.S. EPA was unable to obtain the raw data. However, when the raw data were obtained for the PBDE 209 study (i.e., Viberg et al. 2003) by a third party, who subsequently provided the data to the U.S. EPA, the agency acknowledged that the data were not suitable for use with human health assessment (U.S. EPA 2010). We mention the above information because Herbstman et al. (2010) cited only animal studies that reported PBDE-induced developmental neurotoxicity as support for their work. Although the authors discussed one epidemiological study that reported findings inconsistent with their own, Herbstman et al. (2010) reverted back to the positive animal studies as support for their work. They did not discuss or cite any animal studies that reported contradictory findings. This is significant because it may have introduced a formidable source of bias when Herbstman et al. (2010) were interpreting their results. The exclusion may also mislead the readership of EHP.

A dynamic 4D probabilistic atlas of the developing brain

Probabilistic atlases are widely used in the neuroscience community as a tool for providing a standard space for comparison of subjects and as tissue priors used to enhance the intensity-based classification of brain MRI. Most efforts so far have focused on static brain atlases either for adult or pediatric cohorts. In contrast to the adult brain the rapid growth of the neonatal brain requires an age-specific spatial probabilistic atlas to provide suitable anatomical and structural information. In this paper we describe a 4D probabilistic atlas that allows dynamic generation of prior tissue probability maps for any chosen stage of neonatal brain development between 29 and 44 gestational weeks. The atlas is created from the segmentations of 142 neonatal subjects at different ages using a kernel-based regression method and provides prior tissue probability maps for six structures — cortex, white matter, subcortical grey matter, brainstem, cerebellum and cerebro-spinal fluid. The atlas is publicly available at www.brain-development.org.