Biology subjects

Dewey, D.

Publications and source records attributed to Dewey, D..

14 recordsLinked to original sources

bioRxiv2026

Spatiotemporal Variation in White-Matter Development Across Early Childhood

Early childhood development is scaffolded by rapid maturation of brain white matter structure, believed to support the emergence of cognitive and socioemotional functions. Previous whole-tract studies have suggested patterns of white matter development occurring along posterior-anterior, deep-superficial and inferior-superior axes. However, little is known as to whether these patterns are evident within tracts. Using longitudinal diffusion imaging data from 133 children (4-8 years; 76 females), the present work characterizes along-tract patterns of white matter development across association, commissural and projection bundles using fixel-based analyses of microstructure and macrostructure. Within long range association bundles, faster age-related changes were observed for segments adjacent to the visual cortices relative to segments located near association regions, supporting a sensorimotor-association axis of brain development. An inferior-superior pattern was found for projection tracts, with faster age-effects observed for segments near the brainstem. Lastly, while several association and commissural bundles exhibited faster maturation within central segments; indicative of a deep-superficial axis, effects were mixed between micro- and macrostructure, underscoring the unique developmental timing of these different fiber properties. Our findings provide evidence that within-tract white matter maturation unfolds along key spatiotemporal axes and suggests that increased spatial precision can advance our understanding of early childhood brain development.

neuroscience↗

bioRxiv2025

Feasibility of a parent-delivered attention and working memory intervention for early school-aged children born preterm

Preterm birth is a common neurodevelopmental condition that can have lasting impacts on cognition, including attention and working memory. Interventions that strengthen these skills in early childhood could support school readiness. Dino Island is a tablet-based intervention that combines process-specific practice of attention and working memory skills with a compensatory component that teaches metacognitive skills to scaffold learning. In this pilot study, we evaluated the feasibility of parent-delivered Dino Island in young children born preterm (N=10), alongside a control group who played educational games (N=12). Both groups were instructed to play 2-3 times per week for approximately 20 minutes over a 12-week period. Attention and working memory on untrained tasks were assessed before and after completing the intervention. Parents provided fidelity data through tracking sheets and participated in exit interviews to offer feedback and identify barriers and facilitators. We found that the Dino Island program was successfully delivered by parents with high fidelity. Attrition was higher in the Dino Island group, likely reflecting the challenges of delivering cognitive remediation in home settings. Comparison of attention and working memory scores on untrained tasks pre- and post-showed practice effects but no specific benefit of Dino Island. However, parent reports suggested behavioral improvements specific to the Dino Island group, noting far-transfer effects where children applied metacognitive strategies in other contexts. Overall, this work shows feasibility and tolerability of Dino Island in young children born preterm. Future research should examine its potential impact on school readiness and longer-term academic outcomes in this population.

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bioRxiv2025

Prenatal DEHP plastic chemical exposure increases the likelihood of child autism and ADHD symptoms through epigenetic programming

Increasing evidence implicates prenatal exposure to di-(2-ethylhexyl) phthalate (DEHP), a common endocrine-disrupting plastic chemical, in autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). However, the underlying mechanisms are poorly understood. Here we examined whether cord blood DNA methylation, a key epigenetic marker, mediates the association between prenatal DEHP exposure and ASD/ADHD symptoms in 847 children enrolled in the Barwon Infant Study. ASD and ADHD are complex phenotypes characterised by differences at the gene regulatory network and neuronal circuit level, where heterogeneous genetic and environmental risk factors converge. Accordingly, we employed a data-driven computational strategy that helped elucidate broader functional epigenetic signatures of ASD and ADHD elicited by DEHP exposure. This included (1) a methylation profile score for DEHP exposure (MPSDEHP), and (2) an analysis of co-methylated gene networks. Causal mediation analysis demonstrated that both MPSDEHP and a DEHP-associated network of co-methylated genes mediated the effect of DEHP exposure on increased ASD and ADHD symptoms at ages 2 and 4 years (proportion of effect mediated ranged from 0.21 to 0.80). The co-methylation network was enriched for neural cell-type markers, ASD risk genes (including FOXP1, SHANK2, and PLXNB1), and targets of endocrine receptors previously linked to DEHP (including targets of the estrogen receptor ER and the glucocorticoid receptor GR), providing biological plausibility. We validated key results in independent blood (n=66) and postmortem brain (n=40) DNA methylation datasets. These findings provide mechanistic evidence linking DEHP to ASD and ADHD symptoms and reinforce growing concerns regarding the risks of prenatal exposure.\n\nSignificanceExposure to endocrine-disrupting plastic chemicals has been linked to adverse neurodevelopment, but the underlying biological mechanisms remain unclear. We demonstrate that prenatal exposure to di-(2-ethylhexyl) phthalate (DEHP), a common plasticizer, increases autism and ADHD symptoms through alterations in DNA methylation, a key epigenetic regulator of gene activity. Using birth cohort data, we identify epigenetic signatures of prenatal DEHP exposure, including alterations in an endocrine-related co-methylation network enriched for neural cell-type markers and known autism-associated genes. These signatures mediate the effects of DEHP on autism and ADHD symptoms and are also associated with autism in external blood and postmortem-brain datasets, providing independent validation. This causal evidence further underscores concerns regarding the consequences of prenatal plastic-chemical exposure on the developing brain.

neuroscience↗

bioRxiv2024

Phonological decoding ability is associated with fiber density of the left arcuate fasciculus longitudinally across reading development

Numerous studies have linked reading ability to white matter microstructure using diffusion tensor imaging, but recent large studies have failed to show consistency. Fiber-specific diffusion-weighted magnetic resonance imaging (dMRI) models offer enhanced precision to measure specific features of white matter structure and may be more sensitive to individual differences in reading skills. However, fiber-specific models have not yet been applied to examine associations between reading ability and white matter microstructure over the course of reading acquisition. In this accelerated longitudinal study, we applied constrained spherical deconvolution (CSD) and fiber-specific modelling to characterize developmental changes in fiber density of key white matter tracts of the reading network bilaterally, and investigated associations between tract-wise fiber density and childrens phonological decoding abilities. Fiber density was measured from ages 2-13 years, and decoding ability (pseudoword reading) was assessed at ages 6 years and older. Higher decoding ability was associated with greater fiber density in the left arcuate fasciculus, and effects remained consistent over time. Follow-up analysis revealed that asymmetry changes in the arcuate fasciculus were moderated by decoding ability: good decoders showed leftward asymmetry from early childhood onward, while poorer decoders shifted toward leftward asymmetry over time. These results suggest that densely organized fibers in the left arcuate fasciculus serve as a foundation for the development of reading skills from the pre-reading stage through fluent reading. Ongoing developmental changes in fiber density and microstructural asymmetry throughout childhood may reflect a reciprocal relationship in which reading experience continues to refine and strengthen these pathways.

neuroscience↗

bioRxiv2024

Altered markers of brain metabolism and excitability are associated with executive functioning in young children exposed to alcohol in utero

Prenatal alcohol exposure (PAE) is the leading known cause of birth defects and cognitive disabilities, with impacts on brain development and executive functioning. Abnormalities in structural and functional brain features are well-documented in children with PAE, but the effects of PAE on brain metabolism in children have received less attention. Levels of brain metabolites can be measured non-invasively using magnetic resonance spectroscopy (MRS). Here, we present the first study of PAE-related brain metabolite differences in early childhood (ages 3-8 years) and their associations with cognitive performance, including executive functioning (EF) and pre-reading skills. We measured metabolites in two cohorts of children with PAE and unexposed children using MRS in the anterior cingulate cortex (ACC; cohort 1) and left temporo-parietal cortex (LTP; cohort 2). Total choline (tCho), a marker of membrane/myelin metabolism, was elevated in both regions in children with PAE compared to unexposed children, and glutamate+glutamine (Glx), a marker of excitability, was elevated in the ACC. The PAE group exhibited more difficulties with EF, and higher tCho was associated with better EF in both PAE and unexposed groups. In addition, elevated Glx in the ACC was associated with poorer inhibitory control within the PAE group only. LTP metabolites were not significantly associated with pre-reading skills in PAE or unexposed groups. Together, these findings point to altered membrane metabolism and excitability in young children with PAE. These findings provide new insight to potential mechanisms by which PAE disrupts brain development and cognitive functioning in early childhood.

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bioRxiv2021

Multimodal brain features at preschool age and the relationship with pre-reading measures one year later: an exploratory study

Pre-reading language skills develop rapidly in early childhood and are related to brain structure and function in young children prior to formal education. However, the early neurobiological development that support these skills is not well understood and has not been assessed longitudinally using multiple imaging approaches. 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 one year later (4.5 years). We applied a data-driven linked independent component analysis to explore the shared co-variation of grey and white matter measures. Two sources of structural variation at 3.5 years of age demonstrated a weak relationship 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. 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 (FPL) network and its relationship with pre-reading measures. Higher functional connectivity between the FPL functional network and the default mode and visual networks at 3.5 years 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 grey matter brain structures in early childhood, may support the emergence of pre-reading measures in preschool children.

neuroscience↗

bioRxiv2021

Association between breastfeeding during infancy and white matter microstructure in early childhood

IntroductionAssociations between breastfeeding and brain development, in the context of child, perinatal, and sociodemographic variables, remain unclear. This study investigates whether exclusive breastfeeding for the first 6 months and total duration of any breastfeeding are associated with brain white matter microstructure in young children. MethodsThis study included a sample of 83 mothers and 85 typically developing children (42 males). Children underwent their first diffusion tensor imaging scan between ages 2.34-6.97 years; some children returned multiple times, providing a total of 331 datasets. Feeding information was collected from the mothers at 3, 6, and 12 months postpartum and at their childs 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, a measure sensitive to myelination/axonal packing/fibre coherence) for the whole brain and 10 individual white matter tracts. ResultsBreastfeeding 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. ConclusionsThese 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.

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bioRxiv2020

Benchmarking common preprocessing strategies in early childhood functional connectivity MRI

Functional connectivity magnetic resonance imaging (FC-MRI) has been widely used to investigate neurodevelopment. However, FC-MRI is vulnerable to head motion, which is associated with age and distorts FC estimates. Numerous preprocessing strategies have been developed to mitigate confounds, each with advantages and drawbacks. Preprocessing strategies for FC-MRI have typically been validated and compared using resting state data from adults. However, FC-MRI in young children presents a unique challenge due to relatively high head motion and a growing use of passive viewing paradigms to mitigate motion. This highlights a need to compare processing choices in pediatric samples. To this end, we leveraged longitudinal, passive viewing fMRI data collected from 4 to 8-year-old children. We systematically investigated combinations of widely used and debated preprocessing strategies, namely global signal regression, volume censoring, ICA-AROMA, and bandpass filtering. We implemented commonly used metrics of noise removal (i.e. quality control-functional connectivity), metrics sensitive to individual differences (i.e. connectome fingerprinting), and, because data was collected during a passive viewing task, we also assessed the impact on stimulus-evoked responses (i.e. intersubject correlations; ISC). We found that the most efficacious pipeline included censoring, global signal regression, bandpass filtering, and head motion parameter regression. Despite the drawbacks of noise-mitigation steps, our findings show benefits for both noise removal and information retention in a high-motion early childhood sample. Highlights- We evaluated 27 preprocessing pipelines in passive viewing data from young children - Pipelines were evaluated on noise-removed and information retained - Pipelines that included censoring and GSR outperformed alternatives across benchmarks - For high-motion scans, preprocessing choices substantially alter connectomes

neuroscience↗

bioRxiv2019

Maturation and interhemispheric asymmetry in neurite density and orientation dispersion in early childhood

BackgroundThe brains white matter undergoes profound changes during early childhood, which are believed to underlie the rapid development of cognitive and behavioral skills during this period. Neurite density, and complexity of axonal projections, have been shown to change across the life span, though changes during early childhood are poorly characterized. Here, we utilize neurite orientation dispersion and density imaging (NODDI) to investigate maturational changes in tract-wise neurite density index (NDI) and orientation dispersion index (ODI) during early childhood. Additionally, we assess hemispheric asymmetry of tract-wise NDI and ODI values, and longitudinal changes. MethodsTwo sets of diffusion weighted images (DWI) with different diffusion-weighting were collected from 125 typically developing children scanned at baseline (N=125; age range=4.14-7.29; F/M=73/52), 6-month (N=8; F/M=8/0), and 12-month (N=52; F/M=39/13) timepoints. NODDI and template-based tractography using constrained spherical deconvolution were utilized to calculate NDI and ODI values for major white matter tracts. Mixed-effects models controlling for sex, handedness, and in-scanner head motion were utilized to assess developmental changes in tract-wise NDI and ODI. Paired t-tests were used to assess interhemispheric differences in tract-wise NDI and ODI values and longitudinal changes in cross-sectional and 12-month longitudinal analyses, respectively. ResultsMaturational increases in NDI were seen in all major white matter tracts, though we did not observe the expected tract-wise pattern of maturational rates (e.g. fast commissural/projection and slow frontal/temporal tract change). ODI did not change significantly with age in any tract. We observed higher cross-sectional NDI and ODI values in the right as compared to the left hemisphere for most tracts, but no hemispheric asymmetry for longitudinal changes. ConclusionsThese findings suggest that neurite density, but not orientation dispersion, increases with age during early childhood. In relation to NDI growth trends reported in infancy and late-childhood, our results suggest that early childhood may be a transitional period for neurite density maturation wherein commissural/projection fibers are approaching maturity, maturation in long range association fibers is increasing, and changes in limbic/frontal fibers remain modest. Rightward asymmetry in NDI and ODI values, but not longitudinal changes, suggests that rightward asymmetry of neurite density and orientation dispersion is established prior to age 4.

neuroscience↗

bioRxiv2019

Examining the relationship between prenatal depression, amygdala-prefrontal structural connectivity and behaviour in preschool children

Prenatal depression is a common, underrecognized, and undertreated condition with negative consequences on child behaviour and brain development. Neurological dysfunction of the amygdala, cingulate cortex and hippocampus are associated with the development of depression and stress disorders in youth and adults. Although prenatal depression is associated with both child behaviour and neurological dysfunction, the relationship between these variables remains unclear. In this study, fifty-four mothers completed the Edinburgh Depression Scale (EDS) during the second and third trimester of pregnancy and 3 months postpartum. Their childrens behaviour was assessed using the Child Behaviour Checklist (CBCL), and the children had diffusion magnetic resonance imaging (MRI) at age 4.1 +/- 0.8 years. Associations between prenatal depressive symptoms, child behaviour, and child brain structure were investigated. Third trimester EDS scores were associated with altered white matter in the amygdala-frontal tract and the cingulum, controlling for postpartum depression. Externalizing behaviour was sexually differentiated in the amygdala-frontal pathway. Altered structural connectivity between the amygdala and frontal cortex mediated the relationship between third trimester maternal depressive symptoms and child externalizing behaviour in males, but not females. These findings suggest that altered brain structure is a possible mechanism via which prenatal depressive symptoms can impact child behaviour, highlighting the importance of both recognition and intervention in prenatal depression.

neuroscience↗

bioRxiv2019

Early childhood development of white matter fiber density and morphology

Early childhood is an important period for cognitive and brain development, though white matter changes specific to this period remain understudied. Here we utilize a novel analytic approach to quantify and track developmental changes in white matter micro- and macro-structure, calculated from individually oriented fiber-bundle populations, termed \"fixels\". Fixel-based analysis and mixed-effects models were used to assess tract-wise changes in fiber density and bundle morphology in 73 girls scanned at baseline (ages 4.09-7.02, mean=5.47, SD=0.81), 6-month (N=7), and one-year follow-up (N=42). For comparison, we also assessed changes in commonly utilized diffusion tensor metrics: fractional anisotropy (FA), and mean, radial and axial diffusivity (MD, RD, AD). Maturational increases in fixel-metrics were seen in most major white matter tracts, with the most rapid increases in the corticospinal tract and slowest or non-significant increases in the genu of the corpus callosum and uncinate fasciculi. As expected, we observed developmental increases in FA and decreases in MD, RD and AD, though percentage changes were smaller relative to fixel-metrics. The majority of tracts showed more substantial morphological than microstructural changes. These findings highlight early childhood as a period of dynamic white matter maturation, characterized by large increases in macroscopic fiber bundle size, mild changes in axonal density, and parallel, albeit less substantial, changes in diffusion tensor metrics.

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bioRxiv2019

Global and regional white matter development in early childhood

White matter development continues throughout childhood and into early adulthood, but few studies have examined early childhood, and the specific trajectories and regional variation in this age range remain unclear. The aim of this study was to characterize developmental trajectories and sex differences of white matter in typically developing young children. Three hundred and ninety-six diffusion tensor imaging datasets from 120 children (57 male) aged 2-8 years were analyzed using tractography. Fractional anisotropy (FA) increased and mean diffusivity (MD) decreased in all white matter tracts by 5-15% over the 6-year period, likely reflecting increases in myelination and axonal packing. Males showed steeper slopes in a number of brain areas. Overall, early childhood is associated with substantial development of all white matter and appears to be an important period for the development of occipital and limbic connections, which showed the largest changes. This study provides a detailed characterization of age-related white matter changes in early childhood, offering baseline data that can be used to understand cognitive and behavioural development, as well as to identify deviations from normal development in children with various diseases, disorders, or brain injuries.

neuroscience↗

bioRxiv2018

Time efficient preparation methods for MRI brain scanning in awake young children and factors associated with success

ObjectiveYoung children are often unable to remain still for magnetic resonance imaging (MRI). Various preparation methods have been reported to avoid sedation or anesthesia, with mixed success rates and feasibility. Here we describe a time-efficient preparation method and factors associated with successful scanning in young chdilren.\n\nWe recruited 134 children aged 2.0-5.0 years for an MRI study. Some children completed a training session on a mock scanner, and all children received a 15-20 minute introduction to scanning procedures immediately before their scan. We compared success between children receiving mock scanner training or not, and evaluated demographic or cognitive factors that predicted success.\n\nResults97 children (72%) completed at least one sequence successfully; 64 children provided high-quality data for all 3 sequences. Cognitive scores were higher in successful children, but children who received mock scanner training were less likely to be successful. A case-controlled comparison of children matched on age, gender, and cognitive scores found no differences between children receiving training or not.\n\nWe present a quick method for preparing young children for awake MRI scans. Our data suggests limited advantages of mock scanner preparation for healthy young children, and that cognitive abilities may help predict success.

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bioRxiv2017

Brain white matter structure and language ability in preschool-aged children

Brain alterations are associated with reading and language difficulties in older children, but little research has investigated relationships between early language skills and brain white matter structure during the preschool period. We studied 68 children aged 3.0-5.6 years who underwent diffusion tensor imaging and participated in assessments of Phonological Processing and Speeded Naming. Tract-based spatial statistics and tractography revealed relationships between Phonological Processing and fractional anisotropy and mean diffusivity in bilateral ventral white matter pathways, the corpus callosum, and corticospinal tracts. The relationships observed in left ventral pathways are consistent with studies in older children, and demonstrate that structural markers for language difficulties are apparent as young as 3 years of age. Our findings in right hemisphere areas that are not as commonly found in adult studies suggest that young children rely on a widespread network for language processing that becomes more specialized with age.

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