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2: Visualisation of the 17 white matter tracts derived for analysis, overlaid on the population template. Tracts are 3D representations overlaid on a single representative slice for visualisation. Tracts were derived in FOD template space, using the protocol defined in 1
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The pubertal period involves dynamic white matter development. This period also corresponds with rapid gains in higher cognitive functions including attention, as well as increased risk of developing mental health difficulties. This longitudinal study comprised children aged 9-13 years (n=130). Diffusion magnetic resonance imaging (dMRI) data were...
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Background
Sleep problems are common in adolescence, and frequently comorbid with both anxiety and depression. Research studies have suggested a bidirectional relationship between sleep and psychopathology, which includes evidence that sleep interventions can alleviate symptoms of anxiety and depression. However, little is known about the nature of...
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Background
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Citations
... A linear mixed effects model is a regression model that can account for unequal numbers of data points across participants with unequal time intervals between data points. This model is commonly utilized and ideal for assessing neurodevelopmental growth in cross-lagged longitudinal studies (Genc et al., 2019;Lebel and Beaulieu, 2011;Westerhausen et al., 2016), as it enables inclusion of both cross-sectional and longitudinal data and mitigates participant exclusion when data from all timepoints is unavailable (e.g. due to subject dropout or data quality issues). ...
... These findings differ from those presented here, suggesting that age-related changes in NDI and ODI from birth to early childhood may have a rightward asymmetry to arrive at ubiquitously higher right hemisphere values by approximately age 4, though this hypothesis requires testing. Although there is some conflicting evidence , most studies suggest there are few hemispheric differences in white matter maturation from early childhood to adulthood (Genc et al., 2019;Kodiweera et al., 2016;Beaulieu, 2011, 2009;Takao et al., 2011), which is consistent with our longitudinal findings. Instead, it appears that hemispheric asymmetries in white matter properties emerge primarily during prenatal and early postnatal periods (Dean et al., 2017;Dubois et al., 2009;Song et al., 2015). ...
... White matter tract integrity (WMTI; Fieremans et al., 2011) has been utilized to show developmental increases in axonal water fraction (AWF; a proxy for axonal volume or density) during infancy (Jelescu et al., 2015) and late childhood-adolescence (Huber et al., 2019). Apparent fiber density (AFD; Raffelt et al., 2012), calculated from fiber orientation distributions estimated by constrained spherical deconvolution techniques Jeurissen et al., 2014;Tournier et al., 2007Tournier et al., , 2004 and evaluated using the Fixel-Based Analysis (FBA) framework (Raffelt et al., 2017), has also been shown to increase with age from childhood to adulthood (Dimond et al., 2020;Genc et al., 2019Genc et al., , 2018bGenc et al., , 2018a. In an overlapping sample, we found AFD changes (Dimond et al., 2020) to be less widespread than changes in NDI reported here, with smaller percentage changes (3.1-7.1% for AFD; 7.1-10.1% for NDI) and more variable maturational rates across tracts; AFD increases were rapid in commissural/project fibers and slower in frontal/temporal tracts. ...
Background
The brain's 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.
Methods
Two 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. Additional mixed-effects models were used to assess interhemispheric differences in tract-wise NDI and ODI values and hemispheric asymmetries in tract-wise development.
Results
Maturational 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 greater NDI and ODI values in the right as compared to the left hemisphere for most tracts, but no hemispheric asymmetry for rate of change with age.
Conclusions
These 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 no asymmetry in developmental changes, suggests that rightward asymmetry of neurite density and orientation dispersion is established prior to age 4.
... Diffusion MRI (dMRI) is a technique sensitive to the displacement of water in tissue and allows for the non-invasive approximation of inter-regional white matter fibers integrity. Prior studies focusing on specific tracts or collections of tracts outlined white matter maturation during development based on dMRI parameters of fractional anisotropy and mean diffusivity [26][27][28][29][30][31] . Cross-sectional and longitudinal studies have shown changes in the microstructure of major white matter tracts, often characterized by an increased fractional anisotropy and decreased mean diffusivity from childhood to adolescence [26][27][28]30,32 . ...
... As such, our findings extend prior dMRI studies that have focussed on specific tract groups and that have indicated considerable developmental shifts in diffusion parameters, such as increases in fractional anisotropy and decreases in mean diffusivity in early and late adolescence 32,[78][79][80][81][82][83] . Other studies have furthermore reported increased streamline count estimates 31 . In this context, our macroscale manifold findings likely reflect an ongoing consolidation of transmodal communities. ...
A bstract
Adolescence is a critical time for the continued maturation of brain networks. Here, we assessed structural connectome development in a large longitudinal sample ranging from late child- to young adulthood. Using novel techniques that project high-dimensional connectomes into compact manifold spaces, we could identify a marked expansion of structural connectomes with the strongest effects in transmodal regions during adolescence. Findings were reflected increased within-module connectivity together with increased segregation, indicating an increasing differentiation of higher order association networks from the rest of the brain. Projection of subcortico-cortical connectivity patterns into these manifolds showed parallel alterations in pathways centered on the caudate and thalamus. Connectome findings were contextualized via spatial transcriptome association analysis, highlighting genes enriched in cortex, thalamus, and striatum. Finally, we could show with statistical learning that cortico-subcortical manifold features at baseline and their maturational change predicted measures of intelligence at follow-up, supporting utility of connectome manifolds to bridge structural network reconfigurations and cognitive outcomes in adolescent development.
... We also considered cooccuring dimensions of psychopathology to examine the specificity of white matter microstructure effect to conduct problems. We hypothesised that conduct problems would be cross-sectionally associated with lower FD, with no relationship observed for FC, consistent with research that has linked neurodevelopmental difficulties with decreased white matter fibre density in adolescence, rather than lower macroscopic cross-section of fibres (Dimond et al., 2019;Genc et al., 2020). We also predicted longitudinal relationships such that change in conduct problems across time-points would be associated with FD development within each tract, with no relationship emerging for FC development. ...
... Tournier et al., 2019) using pre-processing steps from a recommended longitudinal fixel-based analysis (FBA) pipeline (Raffelt et al., 2017;Genc et al., 2018). Full details of processing and analysis steps are listed in Genc et al. (2020). Briefly, images were denoised, corrected for motion, eddy current and susceptibility induced distortions, bias field corrected, and upsampled. ...
Childhood conduct problems are an important public health issue as these children are at risk of adverse outcomes. Studies using diffusion Magnetic Resonance Imaging (dMRI) have found that conduct problems in adults are characterised by abnormal white-matter microstructure within a range of white matter pathways underpinning emotional processing, while evidence within children and adolescents has been less conclusive based on non-specific diffusion tensor imaging metrics. Fixel based analysis (FBA) provides measures of fibre density and morphology that are more sensitive to developmental changes in white matter microstructure. The current study used FBA to investigate whether childhood conduct problems were related both cross sectionally and longitudinally to microstructural alterations within the fornix, inferior fronto-occipital fasciculus (IFOF), inferior longitudinal fasciculus (ILF), superior longitudinal fasciculus (SLF), and the uncinate fasciculus (UF). dMRI data was obtained for 130 children across two time-points in a community sample with high levels of externalising difficulties (age: time-point 1 = 9.47 to 11.86 years, time-point 2 = 10.67 to 13.45 years). Conduct problems were indexed at each time-point using the Conduct Problems subscale of the parent-informant Strengths and Difficulties Questionnaire (SDQ). Conduct problems were related to lower fibre density in the fornix at both time-points, and in the ILF at time point 2. We also observed lower fibre cross section in the UF at time-point 1. The change in conduct problems did not predict longitudinal changes in white-matter microstructure across time points. The current study suggests that childhood conduct problems are related to reduced fibre specific microstructure within white matter fibre pathways implicated in emotional functioning.
... Studies utilizing FBA in a neurodevelopmental context suggest white matter development from late childhood to early adulthood may be driven by increases in both axonal packing/density and fiber bundle size (Genc et al., 2017b(Genc et al., , 2018b(Genc et al., , 2018a(Genc et al., , 2019. Age-related increases in axonal packing/density from late childhood to adulthood have also been suggested by studies utilizing an alternative diffusion model, "neurite orientation and dispersion density imaging (NODDI)" (Chang et al., 2015;Genc et al., 2017a;Mah et al., 2017); these changes have been shown to occur alongside increasing FA and decreasing MD during late childhood to adulthood and correlate more strongly with age than DTI metrics (Genc et al., 2017a;Mah et al., 2017). ...
... Linear mixed effects models can also account for unequal numbers of datapoints, and/or unequal time intervals between data points. This type of model is commonly utilized in a neurodevelopmental context to model maturation when there is a variable number of scans available across participants; for example, in cross-lagged longitudinal designs (Genc et al., 2019;Lebel and Beaulieu, 2011;Westerhausen et al., 2016). For all models we included age, handedness, ICV, and total number of signal dropout slices as fixed effects, and participantspecific intercepts as a random effect. ...
... doi: bioRxiv preprint first posted online May. 8, 2019; consistent with longitudinal FBA analyses in older children (aged 9-13), showing FD increases with age in several WM tracts, including the corpus callosum, cingulum bundles, superior longitudinal fasciculi, inferior frontal-occipital fasciculi and corticospinal tracts (Genc et al., 2018b(Genc et al., , 2019. However, our FD findings are less widespread than we hypothesized: we report no significant FD increases in the genu of the corpus callosum, fornix, inferior longitudinal fasciculi, superior longitudinal fasciculi, or uncinate fasciculi. ...
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 longitudinal 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). We also assessed changes in fractional anisotropy (FA) and mean diffusivity (MD). 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 fasciculus. As expected, we observed developmental increases in FA and decreases in MD, though percentage changes were smaller than 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.
Adolescence is a critical time for the continued maturation of brain networks. Here, we assessed structural connectome development in a large longitudinal sample ranging from childhood to young adulthood. By projecting high-dimensional connectomes into compact manifold spaces, we identified a marked expansion of structural connectomes with the strongest effects in transmodal regions during adolescence. Findings reflected increased within-module connectivity together with increased segregation, indicating increasing differentiation of higher-order association networks from the rest of the brain. Projection of subcortico-cortical connectivity patterns into these manifolds showed parallel alterations in pathways centered on the caudate and thalamus. Connectome findings were contextualized via spatial transcriptome association analysis, highlighting genes enriched in cortex, thalamus, and striatum. Statistical learning of cortical and subcortical manifold features at baseline and their maturational change predicted measures of intelligence at follow-up. Our findings demonstrate that connectome manifold learning can bridge the conceptual and empirical gaps between macroscale network reconfigurations, microscale processes, and cognitive outcomes in adolescent development.
