Autism spectrum disorder (ASD) emerges during early childhood and is marked by a relatively narrow window in which infants transition from exhibiting normative behavioral profiles to displaying the ...defining features of the ASD phenotype in toddlerhood. Prospective brain imaging studies in infants at high familial risk for autism have revealed important insights into the neurobiology and developmental unfolding of ASD. In this article, we review neuroimaging studies of brain development in ASD from birth through toddlerhood, relate these findings to candidate neurobiological mechanisms, and discuss implications for future research and translation to clinical practice.
Abstract
Human white matter development in the first years of life is rapid, setting the foundation for later development. Microstructural properties of white matter are linked to many behavioral and ...psychiatric outcomes; however, little is known about when in development individual differences in white matter microstructure are established. The aim of the current study is to characterize longitudinal development of white matter microstructure from birth through 6 years to determine when in development individual differences are established. Two hundred and twenty-four children underwent diffusion-weighted imaging after birth and at 1, 2, 4, and 6 years. Diffusion tensor imaging data were computed for 20 white matter tracts (9 left–right corresponding tracts and 2 commissural tracts), with tract-based measures of fractional anisotropy and axial and radial diffusivity. Microstructural maturation between birth and 1 year are much greater than subsequent changes. Further, by 1 year, individual differences in tract average values are consistently predictive of the respective 6-year values, explaining, on average, 40% of the variance in 6-year microstructure. Results provide further evidence of the importance of the first year of life with regard to white matter development, with potential implications for informing early intervention efforts that target specific sensitive periods.
White matter (WM) integrity has been related to cognitive ability in adults and children, but it remains largely unknown how WM maturation in early life supports emergent cognition. The associations ...between tract‐based measures of fractional anisotropy (FA) and axial and radial diffusivity (AD, RD) shortly after birth, at age 1, and at age 2 and cognitive measures at 1 and 2 years were investigated in 447 healthy infants. We found that generally higher FA and lower AD and RD across many WM tracts in the first year of life were associated with better performance on measures of general cognitive ability, motor, language, and visual reception skills at ages 1 and 2, suggesting an important role for the overall organization, myelination, and microstructural properties of fiber pathways in emergent cognition. RD in particular was consistently related to ability, and protracted development of RD from ages 1 to 2 years in several tracts was associated with higher cognitive scores and better language performance, suggesting prolonged plasticity may confer cognitive benefits during the second year of life. However, we also found that cognition at age 2 was weakly associated with WM properties across infancy in comparison to child and demographic factors including gestational age and maternal education. Our findings suggest that early postnatal WM integrity across the brain is important for infant cognition, though its role in cognitive development should be considered alongside child and demographic factors.
Abstract
Cortical thickness (CT) and surface area (SA) vary widely between individuals and are associated with intellectual ability and risk for various psychiatric and neurodevelopmental conditions. ...Factors influencing this variability remain poorly understood, but the radial unit hypothesis, as well as the more recent supragranular cortex expansion hypothesis, suggests that prenatal and perinatal influences may be particularly important. In this report, we examine the impact of 17 major demographic and obstetric history variables on interindividual variation in CT and SA in a unique sample of 805 neonates who received MRI scans of the brain around 2 weeks of age. Birth weight, postnatal age at MRI, gestational age at birth, and sex emerged as important predictors of SA. Postnatal age at MRI, paternal education, and maternal ethnicity emerged as important predictors of CT. These findings suggest that individual variation in infant CT and SA is explained by different sets of environmental factors with neonatal SA more strongly influenced by sex and obstetric history and CT more strongly influenced by socioeconomic and ethnic disparities. Findings raise the possibility that interventions aimed at reducing disparities and improving obstetric outcomes may alter prenatal/perinatal cortical development.
Cognitive ability is an important predictor of mental health outcomes that is influenced by neurodevelopment. Evidence suggests that the foundational wiring of the human brain is in place by birth, ...and that the white matter (WM) connectome supports developing brain function. It is unknown, however, how the WM connectome at birth supports emergent cognition. In this study, a deep learning model was trained using cross-validation to classify full-term infants (n = 75) as scoring above or below the median at age 2 using WM connectomes generated from diffusion weighted magnetic resonance images at birth. Results from this model were used to predict individual cognitive scores. We additionally identified WM connections important for classification. The model was also evaluated in a separate set of preterm infants (n = 37) scanned at term-age equivalent. Findings revealed that WM connectomes at birth predicted 2-year cognitive score group with high accuracy in both full-term (89.5%) and preterm (83.8%) infants. Scores predicted by the model were strongly correlated with actual scores (r = 0.98 for full-term and r = 0.96 for preterm). Connections within the frontal lobe, and between the frontal lobe and other brain areas were found to be important for classification. This work suggests that WM connectomes at birth can accurately predict a child's 2-year cognitive group and individual score in full-term and preterm infants. The WM connectome at birth appears to be a useful neuroimaging biomarker of subsequent cognitive development that deserves further study.
Resting-state functional MRI (rs-fMRI) is widely used to examine the dynamic brain functional development of infants, but these studies typically require precise cortical parcellation maps, which ...cannot be directly borrowed from adult-based functional parcellation maps due to the substantial differences in functional brain organization between infants and adults. Creating infant-specific cortical parcellation maps is thus highly desired but remains challenging due to difficulties in acquiring and processing infant brain MRIs. In this study, we leveraged 1064 high-resolution longitudinal rs-fMRIs from 197 typically developing infants and toddlers from birth to 24 months who participated in the Baby Connectome Project to develop the first set of infant-specific, fine-grained, surface-based cortical functional parcellation maps. To establish meaningful cortical functional correspondence across individuals, we performed cortical co-registration using both the cortical folding geometric features and the local gradient of functional connectivity (FC). Then we generated both age-related and age-independent cortical parcellation maps with over 800 fine-grained parcels during infancy based on aligned and averaged local gradient maps of FC across individuals. These parcellation maps reveal complex functional developmental patterns, such as changes in local gradient, network size, and local efficiency, especially during the first 9 postnatal months. Our generated fine-grained infant cortical functional parcellation maps are publicly available at https://www.nitrc.org/projects/infantsurfatlas/ for advancing the pediatric neuroimaging field.
White matter (WM) fiber tract differences are present in autism spectrum disorder (ASD) and could be important markers of behavior. One of the earliest phenotypic differences in ASD are language ...atypicalities. Although language has been linked to WM in typical development, no work has evaluated this association in early ASD. Participants came from the Infant Brain Imaging Study and included 321 infant siblings of children with ASD at high likelihood (HL) for developing ASD; 70 HL infants were later diagnosed with ASD (HL-ASD), and 251 HL infants were not diagnosed with ASD (HL-Neg). A control sample of 140 low likelihood infants not diagnosed with ASD (LL-Neg) were also included. Infants contributed expressive language, receptive language, and diffusion tensor imaging data at 6-, 12-, and 24 months. Mixed effects regression models were conducted to evaluate associations between WM and language trajectories. Trajectories of microstructural changes in the right arcuate fasciculus were associated with expressive language development. HL-ASD infants demonstrated a different developmental pattern compared to the HL-Neg and LL-Neg groups, wherein the HL-ASD group exhibited a positive association between WM fractional anisotropy and language whereas HL-Neg and LL-Neg groups showed weak or no association. No other fiber tracts demonstrated significant associations with language. In conclusion, results indicated arcuate fasciculus WM is linked to language in early toddlerhood for autistic toddlers, with the strongest associations emerging around 24 months. To our knowledge, this is the first study to evaluate associations between language and WM development during the pre-symptomatic period in ASD.
•A cortical shape-adaptive kernel is proposed to quantify cortical folding patterns.•The proposed method captures cortical folding in a biologically relevant way.•The proposed method achieves a high ...reproducibility in multi-scan dataset.•Novel associations with demographic effects are revealed in the early postnatal phase.
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The amount of cortical folding, or gyrification, is typically measured within local cortical regions covered by an equidistant geodesic or nearest neighborhood-ring kernel. However, without careful design, such a kernel can easily cover multiple sulcal and gyral regions that may not be functionally related. Furthermore, this can result in smoothing out details of cortical folding, which consequently blurs local gyrification measurements. In this paper, we propose a novel kernel shape to locally quantify cortical gyrification within sulcal and gyral regions. We adapt wavefront propagation to generate a spatially varying kernel shape that encodes cortical folding patterns: neighboring gyral crowns, sulcal fundi, and sulcal banks. For this purpose, we perform anisotropic wavefront propagation that runs fast along gyral crowns and sulcal fundi by solving a static Hamilton–Jacobi partial differential equation. The resulting kernel adaptively elongates along gyral crowns and sulcal fundi, while keeping a uniform shape over flat regions like sulcal banks. We then measure local gyrification within the proposed spatially varying kernel. The experimental results show that the proposed kernel-based gyrification measure achieves a higher reproducibility than the conventional method in a multi-scan dataset. We further apply the proposed kernel to a brain development study in the early postnatal phase from neonate to 2 years of age. In this study we find that our kernel yields both positive and negative associations of gyrification with age, whereas the conventional method only captures positive associations. In general, our method yields sharper and more detailed statistical maps that associate cortical folding with sex and gestational age.
Diffusion Tensor Imaging (DTI) is a non-invasive neuroimaging method that has become the most widely employed MRI modality for investigations of white matter fiber pathways. DTI has proven especially ...valuable for improving our understanding of normative white matter maturation across the life span and has also been used to index clinical pathology and cognitive function. Despite its increasing popularity, especially in pediatric research, the majority of existing studies examining infant white matter maturation depend on regional or white matter skeleton-based approaches. These methods generally lack the sensitivity and spatial specificity of more advanced functional analysis options that provide information about microstructural properties of white matter along fiber bundles. DTI studies of early postnatal brain development show that profound microstructural and maturational changes take place during the first two years of life. The pattern and rate of these changes vary greatly throughout the brain during this time compared to the rest of the life span. For this reason, appropriate image processing of infant MR imaging requires the use of age-specific reference atlases. This article provides an overview of the pre-processing, atlas building, and the fiber tractography procedures used to generate two atlas resources, one for neonates and one for 1- to 2-year-old populations.
the UNC-NAMIC DTI Fiber Analysis Framework, our pediatric atlases provide the computational templates necessary for the fully automatic analysis of infant DTI data. To the best of our knowledge, these atlases are the first comprehensive population diffusion fiber atlases in early pediatric ages that are publicly available.
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