Objectives: Our aim is to understand the effect of the COVID-19 pandemic on families who have been followed longitudinally in two cohorts studied in Alberta, Canada. We will examine household infections during the COVID-19 pandemic, financial impact, domestic violence, substance use, child school and daily life and relationships in the home. We will identify risk and protective factors for maternal mental health outcomes using longitudinal data that can inform policy and government resource allocation in future disasters. Methods: Mothers who are currently participating in two longitudinal studies, Alberta Pregnancy Outcomes and Nutrition (APrON; N = 1,800) and All Our Families (AOF: N = 2,534) were eligible to participate. Mothers were invited to complete the baseline COVID-19 Impact Survey (20-30 min) within 4 months of March 15, 2020, which was when the province of Alberta, Canada, implemented school closures and physical-distancing measures to prevent the spread of COVID-19. Mothers were asked to report on their own, their child's and their family's functioning. Mothers were re-surveyed at 6 months after completion of the initial COVID-19 Impact Survey, and will be re-surveyed again at 12 months. Results: Responses from participants in both cohorts will be examined in harmonized analyses as well as separately. Descriptive, multivariable analysis will be undertaken to examine risk and resiliency over time and factors that predict mental health and well-being. Conclusions: This study will provide timely information on the impact of COVID-19 for Albertan families. It will identify risk and protective factors for mental health and well-being among contemporary urban families supported by a publicly funded health care system to inform allocation of resources to support those most vulnerable during a global pandemic.

Language acquisition occurs rapidly during early childhood and lays the foundation for future reading success. However, little is known about the brain-language relationships in young children. The goal of this study was to investigate relationships between brain metabolites and prereading language abilities in healthy preschool-aged children.

Sophisticated network-based approaches such as structural connectomics may help to detect a biomarker of mild traumatic brain injury (mTBI) in children. This study compared the structural connectome of children with mTBI or mild orthopedic injury (OI) to that of typically developing (TD) children. Children aged 8-16.99 years with mTBI (n = 83) or OI (n = 37) were recruited from the emergency department and completed 3T diffusion MRI 2-20 days postinjury. TD children (n = 39) were recruited from the community and completed diffusion MRI. Graph theory metrics were calculated for the binarized average fractional anisotropy among 90 regions. Multivariable linear regression and linear mixed effects models were used to compare groups, with covariates age, hemisphere, and sex, correcting for multiple comparisons. The two injury groups did not differ on graph theory metrics, but both differed from TD children in global metrics (local network efficiency: TD > OI, mTBI, d = 0.49; clustering coefficient: TD < OI, mTBI, d = 0.49) and regional metrics for the fusiform gyrus (lower degree centrality and nodal efficiency: TD > OI, mTBI, d = 0.80 to 0.96; characteristic path length: TD < OI, mTBI, d = -0.75 to -0.90) and in the superior and middle orbital frontal gyrus, paracentral lobule, insula, and thalamus (clustering coefficient: TD > OI, mTBI, d = 0.66 to 0.68). Both mTBI and OI demonstrated reduced global and regional network efficiency and segregation as compared to TD children. Findings suggest a general effect of childhood injury that could reflect pre- and postinjury factors that can alter brain structure. An OI group provides a more conservative comparison group than TD children for structural neuroimaging research in pediatric mTBI.

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.

Mild traumatic brain injury (mTBI) is highly prevalent, especially in children under 6 years. However, little research focuses on the consequences of mTBI early in development. The objective of the Kids' Outcomes And Long-term Abilities (KOALA) study is to document the impact of early mTBI on children's motor, cognitive, social and behavioural functioning, as well as on quality of life, stress, sleep and brain integrity.

Subtle changes in hippocampal volumes may occur during both physiological and pathophysiological processes in the human brain. Assessing hippocampal volumes manually is a time-consuming procedure, however, creating a need for automated segmentation methods that are both fast and reliable over time. Segmentation algorithms that employ deep convolutional neural networks (CNN) have emerged as a promising solution for large longitudinal neuroimaging studies. However, for these novel algorithms to be useful in clinical studies, the accuracy and reproducibility should be established on independent datasets. Here, we evaluate the performance of a CNN-based hippocampal segmentation algorithm that was developed by Thyreau and colleagues - Hippodeep. We compared its segmentation outputs to manual segmentation and FreeSurfer 6.0 in a sample of 200 healthy participants scanned repeatedly at seven sites across Canada, as part of the Canadian Biomarker Integration Network in Depression consortium. The algorithm demonstrated high levels of stability and reproducibility of volumetric measures across all time points compared to the other two techniques. Although more rigorous testing in clinical populations is necessary, this approach holds promise as a viable option for tracking volumetric changes in longitudinal neuroimaging studies.

Early childhood is an important period of sensory, motor, cognitive and socio-emotional maturation, yet relatively little is known about the brain changes specific to this period. Voxel-based morphometry (VBM) is a technique to estimate regional brain volumes from magnetic resonance (MR) images. The default VBM processing pipeline can be customized to increase accuracy of segmentation and normalization, yet the impact of customizations on analyses in young children are not clear. Here, we assessed the impact of different preprocessing steps on T1-weighted MR images from typically developing children in two separate cohorts. Data were processed with the Computational Anatomy Toolbox (CAT12), using seven different VBM pipelines with distinct combinations of tissue probability maps (TPMs) and DARTEL templates created using the Template-O-Matic, and CerebroMatic. The first cohort comprised female children aged 3.9-7.9 years (N = 62) and the second included boys and girls aged 2.7-8 years (N = 74). We found that pipelines differed significantly in their tendency to classify voxels as grey or white matter and the conclusions about some age effects were pipeline-dependent. Our study helps to both understand age-associations in grey and white matter volume across early childhood and elucidate the impact of VBM customization on brain volumes in this age range.

The impact of the COVID-19 pandemic on alcohol and substance use has been a topic of concern. Pregnant women are currently experiencing elevated anxiety and depression symptoms, which may increase risk of substance use, and potentially result in poor perinatal and neurodevelopmental outcomes for children.

The COVID-19 pandemic has caused substantially elevated distress in pregnant individuals, which has the potential to affect the developing infant brain. Our main objective was to understand how prenatal distress was related to infant brain structure and function and whether social support moderated the associations.

The COVID-19 pandemic and countermeasures implemented by governments around the world have led to dramatically increased symptoms of depression and anxiety. Pregnant individuals may be particularly vulnerable to the negative psychological effects of COVID-19 public health measures because they represent a demographic that is most affected by disasters and because pregnancy itself entails significant life changes that require major psychosocial and emotional adjustments.

Anxiety and depression symptoms in pregnancy typically affect between 10 and 25% of pregnant individuals. Elevated symptoms of depression and anxiety are associated with increased risk of preterm birth, postpartum depression, and behavioural difficulties in children. The current COVID-19 pandemic is a unique stressor with potentially wide-ranging consequences for pregnancy and beyond.

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.

The preschool period is a time of significant physical and behavioral growth, including the improvement of gross and fine motor skills. Although motor development has been comprehensively mapped from infancy to adulthood, the neural correlates associated with motor advancements during early childhood remain unclear. The current study used diffusion tensor imaging (DTI) to delineate key motor pathways and characterize their relationships with motor performance in 80 typically developing preschool children, aged 3-6 years. The Movement Assessment Battery for Children-2nd edition (MABC-II) was used to assess motor functioning. Partial correlations between DTI parameters and motor performance, controlling for sex and age, revealed a positive correlation between motor performance and fractional anisotropy of corpus callosum motor fibers, as well as negative correlations of motor performance with mean and radial diffusivity. These results appear to be driven by females, as correlations were significant in girls but not boys when analyzed separately. Mean corticospinal tract (CST) diffusion parameters were not significantly related to motor performance, but relationships were observed at regionally specific locations along the bilateral CST. These findings suggest preschool-aged children with better motor performance show more mature white matter patterns within motor pathways, and that the structural variation in these pathways may partially account for the natural variability in motor performance.

Perinatal maternal depression is a serious health concern with potential lasting negative consequences for children. Prenatal depression is associated with altered brain gray matter in children, though relations between postpartum depression and children's brains and the role of white matter are unclear.

Developmental lateralization of brain function is imperative for behavioral specialization, yet few studies have investigated differences between hemispheres in structural connectivity patterns, especially over the course of development. The present study compares the lateralization of structural connectivity patterns, or topology, across children, adolescents, and young adults. We applied a graph theory approach to quantify key topological metrics in each hemisphere including efficiency of information transfer between regions (global efficiency), clustering of connections between regions (clustering coefficient [CC]), presence of hub-nodes (betweenness centrality [BC]), and connectivity between nodes of high and low complexity (hierarchical complexity [HC]) and investigated changes in these metrics during development. Further, we investigated BC and CC in seven functionally defined networks. Our cross-sectional study consisted of 211 participants between the ages of 6 and 21 years with 93% being right-handed and 51% female. Global efficiency, HC, and CC demonstrated a leftward lateralization, compared to a rightward lateralization of BC. The sensorimotor, default mode, salience, and language networks showed a leftward asymmetry of CC. BC was only lateralized in the salience (right lateralized) and dorsal attention (left lateralized) networks. Only a small number of metrics were associated with age, suggesting that topological organization may stay relatively constant throughout school-age development, despite known underlying changes in white matter properties. Unlike many other imaging biomarkers of brain development, our study suggests topological lateralization is consistent across age, highlighting potential nonlinear mechanisms underlying developmental specialization.

Adequate cerebral blood flow (CBF) is essential to proper brain development and function. Detailed characterization of CBF developmental trajectories will lead to better understanding of the development of cognitive, motor, and sensory functions, as well as behaviour in children. Previous studies have shown CBF increases during infancy and decreases during adolescence; however, the trajectories during childhood, and in particular the timing of peak CBF, remain unclear. Here, we used arterial spin labeling to map age-related changes of CBF across a large longitudinal sample that included 279 scans on 96 participants (46 girls and 50 boys) aged 2-7 years. CBF maps were analyzed using hierarchical linear regression for every voxel inside the grey matter mask, controlling for multiple comparisons. The results revealed a significant positive linear association between CBF and age in distributed brain regions including prefrontal, temporal, parietal, and occipital cortex, and in the cerebellum. There were no differences in developmental trajectories between males and females. Our findings show that CBF continues to increase until the age of 7 years, likely supporting ongoing improvements in behaviour, cognition, motor, and sensory functions in early childhood.

Prenatal alcohol exposure (PAE) can alter brain development and impact mental health outcomes, and often occurs in conjunction with postnatal adversity (e.g., maltreatment). However, it is unclear how postnatal adverse exposures may moderate mental health and brain outcomes in children with PAE. T1-weighted and diffusion magnetic resonance imaging were obtained from 66 participants aged 7-16 years. Twenty-one participants had PAE and adverse postnatal exposures (PAE+), 12 had PAE without adverse postnatal exposures (PAE-), and 33 were age- and gender-matched controls unexposed to either prenatal alcohol or postnatal adversity. Internalizing and externalizing mental health symptoms were assessed using the Behavioral Assessment System for Children II, Parent-Rating Scale. ANCOVAs were used to compare mental health symptoms, limbic and prefrontal cortical volumes, and diffusion parameters of cortico-limbic white matter tracts between groups, and to assess brain-mental health relationships. Both PAE groups had worse externalizing behavior (higher scores) than controls. The PAE- group had lower fractional anisotropy (FA) in the bilateral cingulum and left uncinate fasciculus, and smaller volumes in the left anterior cingulate cortex than controls and the PAE+ group. The PAE- group also had higher mean diffusivity (MD) in the left uncinate than the PAE+ group, and smaller right anterior cingulate and superior frontal gyrus volumes than controls. These findings show different brain structure and mental health symptom profiles in children with PAE with and without postnatal adversity, highlighting the need to consider adverse postnatal exposures in individuals with PAE.

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.

The COVID-19 pandemic and related public health restrictions have impacted the mental health and coping strategies of many population groups, including people who are pregnant. Our study sought to explore the ways that pregnant people described coping with stressors associated with the pandemic. N = 5879 pregnant individuals completed the pan-Canadian Pregnancy During the COVID-19 Pandemic Survey between April and December 2020. We used descriptive statistics to quantify sociodemographic characteristics and thematic analysis (Braun & Clarke, 2006, 2019) to analyze n = 3316 open-ended text responses to the question "Can you tell us what things you are doing to cope with the COVID-19 pandemic?" The average age of participants was 32 years (SD = 4.4), with the majority identifying as White (83.6%), female (99.7%), married (61.5%), having completed post-secondary education (90.0%), and working full-time (75.4%). We categorized participant responses into two overarching thematic dimensions: (1) ways of coping and (2) coping challenges. Ways of coping included the following main themes: (1) taking care of oneself, (2) connecting socially, (3) engaging in pandemic-specific coping strategies, (4) keeping busy, (5) taking care of others, (6) creating a sense of normalcy, (7) changing perspectives, and (8) practicing spirituality. Coping challenges included the following: (1) the perception of coping poorly, (2) loss of coping methods, (3) managing frontline or essential work, and (4) worries about the future. Findings highlight important implications for targeted prenatal supports delivered remotely, including opportunities for social support, prenatal care, and mental health strategies.

In the largest sample studied to date, white matter microstructural trajectories and their relation to persistent symptoms were examined after pediatric mild traumatic brain injury (mTBI). This prospective, longitudinal cohort study recruited children aged 8-16.99 years with mTBI or mild orthopedic injury (OI) from five pediatric emergency departments. Children's pre-injury and 1-month post-injury symptom ratings were used to classify mTBI with or without persistent symptoms. Children completed diffusion-weighted imaging at post-acute (2-33 days post-injury) and chronic (3 or 6 months via random assignment) post-injury assessments. Mean diffusivity (MD) and fractional anisotropy (FA) were derived for 18 white matter tracts in 560 children (362 mTBI/198 OI), 407 with longitudinal data. Superior longitudinal fasciculus FA was higher in mTBI without persistent symptoms relative to OI, d (95% confidence interval) = 0.31 to 0.37 (0.02, 0.68), across time. In younger children, MD of the anterior thalamic radiations was higher in mTBI with persistent symptoms relative to both mTBI without persistent symptoms, 1.43 (0.59, 2.27), and OI, 1.94 (1.07, 2.81). MD of the arcuate fasciculus, -0.58 (-1.04, -0.11), and superior longitudinal fasciculus, -0.49 (-0.90, -0.09) was lower in mTBI without persistent symptoms relative to OI at 6 months post-injury. White matter microstructural changes suggesting neuroinflammation and axonal swelling occurred chronically and continued 6 months post injury in children with mTBI, especially in younger children with persistent symptoms, relative to OI. White matter microstructure appears more organized in children without persistent symptoms, consistent with their better clinical outcomes.