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IntroductionPrenatal alcohol exposure (PAE) contributes to widespread neurodevelopmental challenges, including reading, and has been associated with altered white matter. Here, we aimed to investigate whether arcuate fasciculus (AF) development is associated with pre-reading language skills in young children with PAE.MethodsA total of 51 children with confirmed PAE (25 males; 5.6 ± 1.1 years) and 116 unexposed controls (57 males; 4.6 ± 1.2 years) underwent longitudinal diffusion tensor imaging (DTI), for a total of 111 scans from participants with PAE and 381 scans in the unexposed control group. We delineated the left and right AF and extracted mean fractional anisotropy (FA) and mean diffusivity (MD). Pre-reading language ability was assessed using age-standardized phonological processing (PP) and speeded naming (SN) scores of the NEPSY-II. Linear mixed effects models were run to determine the relationship between diffusion metrics and age, group, sex, and age-by-group interactions, with subject modeled as a random factor. A secondary mixed effect model analysis assessed the influence of white matter microstructure and PAE on pre-reading language ability using diffusion metric-by-age-by-group interactions, with 51 age- and sex-matched unexposed controls.ResultsPhonological processing (PP) and SN scores were significantly lower in the PAE group (p < 0.001). In the right AF, there were significant age-by-group interactions for FA (p < 0.001) and MD (p = 0.0173). In the left AF, there was a nominally significant age-by-group interaction for MD that failed to survive correction (p = 0.0418). For the pre-reading analysis, a significant diffusion-by-age-by-group interaction was found for left FA (p = 0.0029) in predicting SN scores, and for the right FA (p = 0.00691) in predicting PP scores.DiscussionChildren with PAE showed altered developmental trajectories for the AF, compared with unexposed controls. Children with PAE, regardless of age, showed altered brain-language relationships that resembled those seen in younger typically developing children. Our findings support the contention that altered developmental trajectories in the AF may be associated with functional outcomes in young children with PAE.

Pre-reading language skills develop rapidly in early childhood and are related to brain structure and functional architecture in young children prior to formal education. However, the early neurobiological development that supports these skills is not well understood. Here we acquired anatomical, diffusion tensor imaging (DTI) and resting state functional MRI (rs-fMRI) from 35 children at 3.5 years of age. Children were assessed for pre-reading abilities using the NEPSY-II subtests 1 year later (4.5 years). We applied a data-driven linked independent component analysis (ICA) to explore the shared co-variation of gray and white matter measures. Two sources of structural variation at 3.5 years of age demonstrated relationships with Speeded Naming scores at 4.5 years of age. The first imaging component involved volumetric variability in reading-related cortical regions alongside microstructural features of the superior longitudinal fasciculus (SLF). The second component was dominated by cortical volumetric variations within the cerebellum and visual association area. In a subset of children with rs-fMRI data, we evaluated the inter-network functional connectivity of the left-lateralized fronto-parietal language network (FPL) and its relationship with pre-reading measures. Higher functional connectivity between the FPL and the default mode and visual networks at 3.5 years significantly predicted better Phonological Processing scores at 4.5 years. Together, these results suggest that the integration of functional networks, as well as the co-development of white and gray matter brain structures in early childhood, support the emergence of pre-reading measures in preschool children.

Intra-individual transient temporal fluctuations in brain signal, as measured by fMRI blood oxygenation level dependent (BOLD) variability, is increasingly considered an important signal rather than measurement noise. Evidence from computational and cognitive neuroscience suggests that signal variability is a good proxy-measure of brain functional integrity and information processing capacity. Here, we sought to explore across-participant and longitudinal relationships between BOLD variability, age, and white matter structure in early childhood. We measured standard deviation of BOLD signal, total white matter volume, global fractional anisotropy (FA) and mean diffusivity (MD) during passive movie viewing in a sample of healthy children (aged 2–8 years; N = 83). We investigated how age and white matter development related to changes in BOLD variability both across- and within-participants. Our across-participant analyses using behavioural partial least squares (bPLS) revealed that the influence of age and white matter maturation on BOLD variability was highly interrelated. BOLD variability increased in widespread frontal, temporal and parietal regions, and decreased in the hippocampus and parahippocampal gyrus with age and white matter development. Our longitudinal analyses using linear mixed effects modelling revealed significant associations between BOLD variability, age and white matter microstructure. Analyses using artificial neural networks demonstrated that BOLD variability and white matter micro and macro-structure at earlier ages were strong predictors of BOLD variability at later ages. By characterizing the across-participant and longitudinal features of the association between BOLD variability and white matter micro- and macrostructure in early childhood, our results provide a novel perspective to understand structure-function relationships in the developing brain.

White matter bundle segmentation using diffusion MRI fiber tractography has become the method of choice to identify white matter fiber pathways in vivo in human brains. However, like other analyses of complex data, there is considerable variability in segmentation protocols and techniques. This can result in different reconstructions of the same intended white matter pathways, which directly affects tractography results, quantification, and interpretation. In this study, we aim to evaluate and quantify the variability that arises from different protocols for bundle segmentation. Through an open call to users of fiber tractography, including anatomists, clinicians, and algorithm developers, 42 independent teams were given processed sets of human whole-brain streamlines and asked to segment 14 white matter fascicles on six subjects. In total, we received 57 different bundle segmentation protocols, which enabled detailed volume-based and streamline-based analyses of agreement and disagreement among protocols for each fiber pathway. Results show that even when given the exact same sets of underlying streamlines, the variability across protocols for bundle segmentation is greater than all other sources of variability in the virtual dissection process, including variability within protocols and variability across subjects. In order to foster the use of tractography bundle dissection in routine clinical settings, and as a fundamental analytical tool, future endeavors must aim to resolve and reduce this heterogeneity. Although external validation is needed to verify the anatomical accuracy of bundle dissections, reducing heterogeneity is a step towards reproducible research and may be achieved through the use of standard nomenclature and definitions of white matter bundles and well-chosen constraints and decisions in the dissection process.

Introduction: Associations between breastfeeding and brain development, in the context of child, perinatal, and sociodemographic variables, remain unclear. This study investigated whether exclusive breastfeeding for the first 6 months and total duration of breastfeeding were associated with brain white matter microstructure in young children. Methods: This study included 85 typically developing children (42 males) born to 83 mothers that were predominantly white, highly educated, and in high income households. Children underwent their first diffusion tensor imaging scan between ages 2.34 and 6.97 years; some children returned multiple times, providing a total of 331 datasets. Feeding information was collected from mothers at 3, 6, and 12 months postpartum and at their child's scan to calculate breastfeeding status at 6 months (exclusive or not) as well as total duration of any breastfeeding. Linear regression was used to investigate associations between breastfeeding exclusivity/duration and fractional anisotropy (FA) for the whole brain and 10 individual white matter tracts. Results: Breastfeeding exclusivity and duration were associated with global and regional white matter microstructure, even after controlling for perinatal and sociodemographic factors. Greater exclusivity was associated with higher FA in females and lower FA in males. Conclusions: These findings suggest white matter differences associated with breastfeeding that differ by sex. These may stem from different trajectories in white matter development between males and females in early childhood and suggest possible long-term white matter differences associated with breastfeeding.

Abstract Background Bisphenol A (BPA) is commonly used in the manufacture of plastics and epoxy resins. In North America, over 90% of the population has detectable levels of urinary BPA. Human epidemiological studies have reported adverse behavioral outcomes with BPA exposure in children, however, corresponding effects on children’s brain structure have not yet been investigated. The current study examined the association between prenatal maternal and childhood BPA exposure and white matter microstructure in children aged 2 to 5 years, and investigated whether brain structure mediated the association between BPA exposure and child behavior. Methods Participants were 98 mother-child pairs who were recruited between January 2009 and December 2012. Total BPA concentrations in spot urine samples obtained from mothers in the second trimester of pregnancy and from children at 3–4 years of age were analyzed. Children participated in a diffusion magnetic resonance imaging (MRI) scan at age 2–5 years (3.7 ± 0.8 years). Associations between prenatal maternal and childhood BPA and children’s fractional anisotropy and mean diffusivity of 10 isolated white matter tracts were investigated, controlling for urinary creatinine, child sex, and age at the time of MRI. Post-hoc analyses examined if alterations in white matter mediated the relationship of BPA and children’s scores on the Child Behavior Checklist (CBCL). Results Prenatal maternal urinary BPA was significantly associated with child mean diffusivity in the splenium and right inferior longitudinal fasciculus. Splenium diffusivity mediated the relationship between maternal prenatal BPA levels and children’s internalizing behavior (indirect effect: β = 0.213, CI [0.0167, 0.564]). No significant associations were found between childhood BPA and white matter microstructure. Conclusions This study provides preliminary evidence for the neural correlates of BPA exposure in humans. Our findings suggest that prenatal maternal exposure to BPA may lead to alterations in white matter microstructure in preschool aged children, and that such alterations mediate the relationship between early life exposure to BPA and internalizing problems.

The Calgary Preschool MRI Dataset in the Developmental Neuroimaging Lab at the University of Calgary uses magnetic resonance imaging (MRI) techniques to study brain structure and function in early childhood [1–3]. The dataset aims to characterise brain development in early childhood (2–8 years), and to understand links to cognitive and behavioral development, as well as provide a baseline from which to identify atypical development in children with diseases, disorders, or brain injuries. MRI data are provided for 126 children (61 males, 65 females). Children ranged from 1.95 to 6.22 years (mean = 3.98 ± 1.06 years) at the time of their first scan and were initially scanned at six month intervals, and now continue to be followed annually (1–20 scans per child, 431 total datasets; datasets do not always have all scan modalities available). All MRI scans were acquired on the same General Electric 3T MR750w system and 32-channel head coil (GE, Waukesha, WI) at the Alberta Children's Hospital in Calgary, Canada. The MRI protocols provided in this dataset include: T1-weighted images acquired using a FSPGR BRAVO sequence; arterial spin labeling (ASL) images acquired with the vendor supplied pseudo continuous 3D ASL sequence; diffusion tensor imaging data acquired using single shot spin echo echo-planar imaging; and passive viewing resting state functional MRI data acquired with a gradient-echo echo-planar imaging sequence. Keywords: Magnetic resonance imaging, Arterial spin labeling, Cerebral blood flow, Diffusion tensor imaging, Resting state fMRI, Passive viewing fMRI, Neurodevelopment, Early childhood

Structural and functional neuroimaging studies show language and reading processes are left-lateralized, and associated with a dispersed group of left brain regions. However, it is unclear when and how asymmetry of these regions emerges. We characterized the development of structural and functional asymmetry of the language network in 386 datasets from 117 healthy children (58 male) across early childhood (2–7.5 years). Structural asymmetry was investigated using diffusion tensor imaging (DTI) and manual delineation of the arcuate fasciculus. Functional connectivity asymmetry was calculated from seed regions in the inferior frontal gyrus (IFG) and middle temporal gyrus (MTG). We show that macrostructural asymmetry of the arcuate fasciculus is present by age 2 years, while leftward asymmetry of microstructure and functional connectivity with the IFG increases across the age range. This emerging microstructural and functional asymmetry likely underlie the development of language and reading skills during this time. Keywords: Diffusion tensor imaging, Resting State fMRI, Asymmetry, Lateralization, Prereading, Arcuate Fasciculus

This study aimed to explore the rates of motor difficulties in children from the Australian Autism Biobank, and how early motor concerns impacted on children functionally. Children with autism aged 2-7 years, including 441 with a Vineland Adaptive Behavior Scale (VABS-II) motor subscale and 385 with a Mullen Scales of Early Learning (MSEL) fine motor subscale were included (n total = 514; 80% male). Approximately 60% of children on the MSEL and ~ 25% on the VABS-II had clinically significant motor impairments. More children with delayed sitting and walking motor milestones had early childhood parent reported motor difficulties (p < 0.001). Early motor delays or concerns may assist identifying individuals who will likely benefit from early ongoing developmental monitoring and early support.

Reading disorders are common in children and can impact academic success, mental health, and career prospects. Reading is supported by network of interconnected left hemisphere brain regions, including temporo-parietal, occipito-temporal, and inferior-frontal circuits. Poor readers often show hypoactivation and reduced gray matter volumes in this reading network, with hyperactivation and increased volumes in the posterior right hemisphere. We assessed gray matter development longitudinally in pre-reading children aged 2-5 years using magnetic resonance imaging (MRI) (N = 32, 110 MRI scans; mean age: 4.40 ± 0.77 years), half of whom had a family history of reading disorder. The family history group showed slower proportional growth (relative to total brain volume) in the left supramarginal and inferior frontal gyri, and faster proportional growth in the right angular, right fusiform, and bilateral lingual gyri. This suggests delayed development of left hemisphere reading areas in children with a family history of dyslexia, along with faster growth in right homologues. This alternate development pattern may predispose the brain to later reading difficulties and may later manifest as the commonly noted compensatory mechanisms. The results of this study further shows our understanding of structural brain alterations that may form the neurological basis of reading difficulties.

Naturalistic developmental behavioural interventions are promising approaches for young children with, or suspected of having, autism spectrum disorder. Joint attention, symbolic play, engagement and regulation intervention (JASPER) is a well-researched naturalistic developmental behavioural intervention but, to date, no reviews have specifically evaluated its effects. This systematic literature review examined the effects of JASPER intervention and its components on child, parent and educator outcomes. Of the 96 articles screened, 19 were eligible for inclusion in the review. Most studies found that children who received JASPER intervention showed significantly greater improvements in at least one outcome related to child joint attention, joint engagement, play skills and language skills compared to the comparison group. Implementation outcomes for parents and educators were generally positive. There were no consistent predictors or mediators of treatment effects. None of the studies met all of the quality indicators outlined by the Council of Exceptional Children, and the majority of outcome measures were classified as proximal. Overall, JASPER intervention appears promising in improving child outcomes directly targeted during treatment. More research is needed to determine whether it is also effective in improving a wider range of outcomes for children with autism spectrum disorder.

Fronto-limbic white matter (WM) abnormalities are assumed to lie at the heart of the pathophysiology of bipolar disorder (BD); however, diffusion tensor imaging (DTI) studies have reported heterogeneous results and it is not clear how the clinical heterogeneity is related to the observed differences. This study aimed to identify WM abnormalities that differentiate patients with BD from healthy controls (HC) in the largest DTI dataset of patients with BD to date, collected via the ENIGMA network. We gathered individual tensor-derived regional metrics from 26 cohorts leading to a sample size of N = 3033 (1482 BD and 1551 HC). Mean fractional anisotropy (FA) from 43 regions of interest (ROI) and average whole-brain FA were entered into univariate mega- and meta-analyses to differentiate patients with BD from HC. Mega-analysis revealed significantly lower FA in patients with BD compared with HC in 29 regions, with the highest effect sizes observed within the corpus callosum (R2 = 0.041, Pcorr

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The lateral angle method of sex estimation is tested on an archaeological population with genetic sex estimates. Casts of the internal auditory canal were made using a quick drying impression material on 90 individuals (76 adults and 14 nonadults) from Anglo‐Saxon and Medieval Cambridgeshire. The anterior and posterior angles of the internal auditory canal were measured, and the relationship of the angle to genetic sex was tested. The posterior angle failed intra‐observer error tests, and only the anterior angle could be analysed. Using the previously published sectioning point for unburnt remains (45°), the method did not adequately distinguish between the sexes. Furthermore, the difference between male and female was insufficient to create population‐specific discriminant functions. The anterior angle does not meet the requirements for an osteological method of sex estimation, exhibiting no statistical correlation with genetic sex in this population. [ABSTRACT FROM AUTHOR]