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Background and ObjectivesTo investigate brain regional white matter development in full-term (FT) and very preterm (VP) children at term equivalent and 7 and 13 years of age based on the ratio of T1- and T2-weighted MRI (T1-w/T2-w), including (1) whether longitudinal changes differ between birth groups or sexes, (2) associations with perinatal risk factors in VP children, and (3) relationships with neurodevelopmental outcomes at 13 years.MethodsProspective longitudinal cohort study of VP (born T1-w/T2-w images were parcellated into 48 white matter regions of interest.ResultsOf 224 VP participants and 76 FT participants, 197 VP and 55 FT participants had useable T1-w/T2-w data from at least one timepoint. T1-w/T2-w values increased between term equivalent and 13 years of age, with little evidence that longitudinal changes varied between birth groups or sexes. VP birth, neonatal brain abnormalities, being small for gestational age, and postnatal infection were associated with reduced regional T1-w/T2-w values in childhood and adolescence. Increased T1-w/T2-w values across the white matter at 13 years were associated with better motor and working memory function for all children. Within the FT group only, larger increases in T1-w/T2-w values from term equivalent to 7 years were associated with poorer attention and executive function, and higher T1-w/T2-w values at 7 years were associated with poorer mathematics performance.DiscussionVP birth and multiple known perinatal risk factors are associated with long-term reductions in the T1-w/T2-w ratio in white matter regions in childhood and adolescence, which may relate to alterations in microstructure and myelin content. Increased T1-w/T2-w ratio at 13 years appeared to be associated with better motor and working memory function and there appeared to be developmental differences between VP and FT children in the associations for attention, executive functioning, and mathematics performance.

OBJECTIVE: Evaluate longitudinal changes in brain microstructure and volumes in very preterm during the first year of life with and without intervention. DESIGN: Descriptive pilot study METHODS: Five preterm infants in a three-arm clinical trial, one SPEEDI Early, two SPEEDI Late, and two usual care. Brain structural and diffusion MRI’s were acquired within 72 hours after neonatal intensive care unit discharge (n=5), three months post-baseline (n=5), and six months post-baseline (n=3). Fractional anisotropy (FA), Mean diffusivity (MD), and volume metrics were computed for five brain regions. RESULTS: More than 60% of eligible participants completed 100% of the scheduled MRIs. FA and volume increased from baseline to six months across all brain regions. Rate of white matter volume change from baseline to six months was highest in SPEEDI Early. CONCLUSIONS: Non-sedated longitudinal MRI is feasible in very preterm infants and appears to demonstrate longitudinal changes in brain structure and connectivity.

Children born extremely preterm (EP

Very preterm (VP) children are at risk of memory and emotional impairments; however, the neural correlates remain incompletely defined. This study investigated the effect of VP birth on white matter tracts traditionally related to episodic memory and emotion.The cingulum, fornix, uncinate fasciculus, medial forebrain bundle and anterior thalamic radiation were reconstructed using tractography in 144 VP children and 33 full-term controls at age 7 years.Compared with controls, VP children had higher axial, radial, and mean diffusivities and neurite orientation dispersion, and lower volume and neurite density in the fornix, along with higher neurite orientation dispersion in the medial forebrain bundle. Support vector classification models based on tract measures significantly classified VP children and controls. Higher fractional anisotropy and lower diffusivities in the cingulum, uncinate fasciculus, medial forebrain bundle and anterior thalamic radiation were associated with better episodic memory, independent of key perinatal risk factors. Support vector regression models using tract measures did not predict episodic memory and emotional outcomes.Altered tract structure is related to adverse episodic memory outcomes in VP children, but further research is required to determine the ability of tract structure to predict outcomes of individual children.We studied white matter fibre tracts thought to be involved in episodic memory and emotion in VP and full-term children using diffusion magnetic resonance imaging and machine learning. VP children have altered fornix and medial forebrain bundle structure compared with full-term children. Altered tract structure can be detected using machine learning, which accurately classified VP and full-term children using tract data. Altered cingulum, uncinate fasciculus, medial forebrain bundle and anterior thalamic radiation structure was associated with poorer episodic memory skills using linear regression. The ability of tract structure to predict episodic memory and emotional outcomes of individual children based on support vector regression was limited.

ObjectiveTo explore whether regional brain volume and white matter microstructure at term-equivalent age (TEA) are associated with development at 2 years of age in children born moderate–late preterm (MLPT).Study designA cohort of MLPT infants had brain MRI at approximately TEA (38–44 weeks’ postmenstrual age) and had a developmental assessment (Bayley Scales of Infant and Toddler Development and Infant Toddler Social Emotional Assessment) at 2 years’ corrected age. Relationships between cortical grey matter and white matter volumes and 2-year developmental outcomes were explored using voxel-based morphometry. Relationships between diffusion tensor measures of white matter microstructure (fractional anisotropy (FA) and axial (AD), radial (RD) and mean (MD) diffusivities) and 2-year developmental outcomes were explored using tract-based spatial statistics.Results189 MLPT children had data from at least one MRI modality (volumetric or diffusion) and data for at least one developmental domain. Larger cortical grey and white matter volumes in many brain regions, and higher FA and lower AD, RD and MD in several major white matter regions, were associated with better cognitive and language scores. There was little evidence that cortical grey matter and white matter volumes and white matter microstructure were associated with motor and behavioural outcomes.ConclusionsRegional cortical grey matter and white matter volumes and white matter microstructure are associated with cognitive and language development at 2 years of age in MLPT children. Thus, early alterations to brain volumes and microstructure may contribute to some of the developmental deficits described in MLPT children.

Attention deficits are common in children born very preterm (VP), especially for children with higher social risk. The aim of this study was to examine the association between parenting behavior and attention in children born VP, and whether this association is influenced by familial social risk. Two hundred and twenty-four children born30 weeks' gestation and/or with a birth weight1250 g were recruited at birth. At 2 years, social risk was calculated and parenting behaviors were observed during a parent-child interaction task, with children's attention skills assessed at 7 and 13 years using standardized assessments. Higher levels of sensitive parenting at 2 years were positively associated with divided attention at age 7 years, and higher levels of intrusive parenting were negatively associated with divided attention at 13 years. Children born VP with higher social risk were more positively influenced by sensitive parenting behavior for sustained attention at 7 years, selective attention at 13 years, and divided attention at 7 and 13 years than children born VP with lower social risk. Additionally, children born VP with higher social risk were more negatively influenced by intrusive parenting for sustained attention outcomes at 7 years than those with lower social risk. In summary, the evidence for a contribution of early parenting to attention outcomes in children born VP was stronger for more complex attention (divided attention) compared with basic attention domains. Our findings also suggest that early parenting behavior has a particular influence on children born VP from socially disadvantaged environments for attention outcomes.

Tensor-based investigations suggest that delayed or disrupted white matter development may relate to adverse behavioral outcomes in individuals born very preterm (VP); however, metrics derived from such models lack specificity. Here, we applied a fixel-based analysis framework to examine white matter microstructural and macrostructural correlates of concurrent internalizing and externalizing problems in VP and full-term (FT) children at 7 and 13 years.Diffusion imaging data were collected in a longitudinal cohort of VP and FT individuals (130 VP and 29 FT at 7 years, 125 VP and 44 FT at 13 years). Fixel-based measures of fiber density, fiber-bundle cross-section, and fiber density and cross-section were extracted from 21 white matter tracts previously implicated in psychopathology. Internalizing and externalizing symptoms were assessed using the Strengths and Difficulties Questionnaire parent report at 7 and 13 years.At age 7 years, widespread reductions in fiber-bundle cross-section and fiber density and cross-section and tract-specific reductions in fiber density were related to more internalizing and externalizing symptoms irrespective of birth group. At age 13 years, fixel-based measures were not related to internalizing symptoms, while tract-specific reductions in fiber density, fiber-bundle cross-section, and fiber density and cross-section measures were related to more externalizing symptoms in the FT group only.Age-specific neurobiological markers of internalizing and externalizing problems identified in this study extend previous tensor-based findings to inform pathophysiological models of behavior problems and provide the foundation for investigations into novel preventative and therapeutic interventions to mitigate risk in VP and other high-risk infant populations.

The emerging field of geometric deep learning extends the application of convolutional neural networks to irregular domains such as graphs, meshes and surfaces. Several recent studies have explored the potential for using these techniques to analyse and segment the cortical surface. However, there has been no comprehensive comparison of these approaches to one another, nor to existing Euclidean methods, to date. This paper benchmarks a collection of geometric and traditional deep learning models on phenotype prediction and segmentation of sphericalised neonatal cortical surface data, from the publicly available Developing Human Connectome Project (dHCP). Tasks include prediction of postmenstrual age at scan, gestational age at birth and segmentation of the cortical surface into anatomical regions defined by the M-CRIB-S atlas. Performance was assessed not only in terms of model precision, but also in terms of network dependence on image registration, and model interpretation via occlusion. Networks were trained both on sphericalised and anatomical cortical meshes. Findings suggest that the utility of geometric deep learning over traditional deep learning is highly task-specific, which has implications for the design of future deep learning models on the cortical surface. The code, and instructions for data access, are available from https://github.com/Abdulah-Fawaz/Benchmarking-Surface-DL.

Infants born very preterm (VPT; ≤29 weeks of gestation) are at high risk of developmental disabilities and abnormalities in neural white matter characteristics. Early physical therapy interventions such as Supporting Play Exploration and Early Development Intervention (SPEEDI2) are associated with improvements in developmental outcomes. Six VPT infants were enrolled in a randomised clinical trial of SPEEDI2 during the transition from the neonatal intensive care unit to home over four time points. Magnetic resonance imaging scans and fixel-based analysis were performed, and fibre density (FD), fibre cross-section (FC), and fibre density and cross-section values (FDC) were computed. Changes in white matter microstructure and macrostructure were positively correlated with cognitive, motor, and motor-based problem solving over time on developmental assessments. In all infants, the greatest increase in FD, FC, and FDC occurred between Visit 1 and 2 (mean chronological age: 2.68–6.22 months), suggesting that this is a potential window of time to optimally support adaptive development. Results warrant further studies with larger groups to formally compare the impact of intervention and disparity on neurodevelopmental outcomes in infants born VPT.

There have been many studies demonstrating children born very preterm exhibit brain white matter microstructural alterations, which have been related to neurodevelopmental difficulties. These prior studies have often been based on diffusion MRI modelling and analysis techniques, which commonly focussed on white matter microstructural properties in children born very preterm. However, there have been relatively fewer studies investigating the free-water content of the white matter, and also the microstructure and free-water content of the cortical grey matter, in children born very preterm. These biophysical properties of the brain change rapidly during fetal and neonatal brain development, and therefore such properties are likely also adversely affected by very preterm birth. In this study, we investigated the relationship of very preterm birth (30 weeks' gestation) to both white matter and cortical grey matter microstructure and free-water content in childhood using advanced diffusion MRI analyses. A total of 130 very preterm participants and 45 full-term control participants underwent diffusion MRI at age 13 years. Diffusion tissue signal fractions derived by Single-Shell 3-Tissue Constrained Spherical Deconvolution were used to investigate brain tissue microstructural and free-water composition. The tissue microstructural and free-water composition metrics were analysed using a voxel-based analysis and cortical region-of-interest analysis approach. Very preterm 13-year-olds exhibited reduced white matter microstructural density and increased free-water content across widespread regions of the white matter compared with controls. Additionally, very preterm 13-year-olds exhibited reduced microstructural density and increased free-water content in specific temporal, frontal, occipital and cingulate cortical regions. These brain tissue composition alterations were strongly associated with cerebral white matter abnormalities identified in the neonatal period, and concurrent adverse cognitive and motor outcomes in very preterm children. The findings demonstrate brain microstructural and free-water alterations up to thirteen years from neonatal brain abnormalities in very preterm children that relate to adverse neurodevelopmental outcomes.

ObjectiveNeonatal conditions can have lifelong implications for the health and well-being of children and families. Traditionally, parents and patients have not been included in shaping the agenda for research and yet they are profoundly affected by the neonatal experience and its consequences. This study aimed to identify consensus research priorities among parents/patients of newborn medicine in Australia and New Zealand.DesignParents/patients with experience of neonatal care in Australia and New Zealand completed an online Delphi study to identify research priorities across four epochs (neonatal admission, early childhood, childhood/adolescence and adulthood). Parents/patients first generated key challenges in each of these epochs. Through inductive thematic analysis, recurring topics were identified and research questions generated. Parents/patients rated these questions in terms of priorities and a list of questions consistently rated as high priority was identified.Participants393 individuals participated, 388 parents whose children had received neonatal care and 5 adults who had received neonatal care themselves.ResultsMany research questions were identified as high-priority across the lifespan. These included how to best support parental mental health, relationships between parents and neonatal clinical staff (including involvement in care and communication), bonding and the parent–child relationship, improving neonatal medical care and addressing long-term impacts on child health and neurodevelopment.ConclusionsParents with experience of newborn medicine have strong, clear and recurring research priorities spanning neonatal care practices, psychological and other impacts on families, and impacts on child development. These findings should guide neonatal research efforts. In addition to generating new knowledge, improved translation of existing evidence to parents is also needed.

Very preterm birth (VP;32 weeks' gestation) is associated with altered brain gray matter development and lower math ability. In typically developing children, the neural correlates of math ability may change dynamically with age, though evidence in VP children is limited. In a prospective longitudinal cohort of children born VP and full term (FT), we aimed to investigate associations between 1) concurrent regional brain volumes and math ability at 7 (n = 148 VP; n = 34 FT) and 13-years (n = 130 VP; n = 46 FT), and 2) regional volumetric growth across childhood (term-equivalent age (TEA) to 7-years; 7 to 13-years) and math ability from 7 to 13-years, and improvement in ability from 7 to 13 years. For both aims we investigated whether associations differed between birth groups. Cross-sectionally, frontal, temporal and subcortical regional volumes were positively associated with math ability for both birth groups. For FT children, greater growth of specific temporal regions was associated with higher math ability, and greater improvements. For VP children, similar associations were only observed for growth from TEA to 7-years with 13-year ability and improvements in ability. In conclusion, VP birth appears to alter associations of brain development across the first 13 years with childhood math ability.

Background Children born very preterm (VP) are at higher risk of emotional and behavioral problems compared with full-term (FT) children. We investigated the neurobiological basis of internalizing and externalizing symptoms in individuals born VP and FT by applying a graph theory approach. Methods Structural and diffusion MRI data were combined to generate structural connectomes and calculate measures of network integration and segregation at 7 (VP:72; FT:17) and 13 years (VP:125; FT:44). Internalizing and externalizing were assessed at 7 and 13 years using the Strengths and Difficulties Questionnaire. Linear regression models were used to relate network measures and internalizing and externalizing symptoms concurrently at 7 and 13 years. Results Lower network integration (characteristic path length and global efficiency) was associated with higher internalizing symptoms in VP and FT children at 7 years, but not at 13 years. The association between network integration (characteristic path length) and externalizing symptoms at 7 years was weaker, but there was some evidence for differential associations between groups, with lower integration in the VP and higher integration in the FT group associated with higher externalizing symptoms. At 13 years, there was some evidence that associations between network segregation (average clustering coefficient, transitivity, local efficiency) and externalizing differed between the VP and FT groups, with stronger positive associations in the VP group. Conclusions This study provides insights into the neurobiological basis of emotional and behavioral problems following preterm birth, highlighting the role of the structural connectome in internalizing and externalizing symptoms in childhood and adolescence.

Highlights • White matter micro and macrostructure are associated with math computation ability. • Faster white matter maturation is associated with greater gains in math computation. • White matter-math associations were similar for very preterm and term children., Children born very preterm (VPT

Brain atlases providing standardised identification of neonatal brain regions are key in investigating neurological disorders of early childhood. Our previously developed Melbourne Children's Regional Infant Brain (M‐CRIB) and M‐CRIB 2.0 neonatal brain atlases provide standardised parcellation of 100 brain regions including cortical, subcortical, and cerebellar regions. The aim of this study was to extend M‐CRIB atlas coverage to include 54 white matter (WM) regions. Participants were 10 healthy term‐born neonates that were used to create the initial M‐CRIB atlas. WM regions were manually segmented based on T 2 images and co‐registered diffusion tensor imaging‐based, direction‐encoded colour maps. Our labelled regions imitate the Johns Hopkins University neonatal atlas, with minor anatomical modifications. All segmentations were reviewed and approved by a paediatric radiologist and a neurosurgery research fellow for anatomical accuracy. The resulting neonatal WM atlas comprises 54 WM regions: 24 paired regions, and six unpaired regions comprising five corpus callosum subdivisions, and one pontine crossing tract. Detailed protocols for manual WM parcellations are provided, and the M‐CRIB‐WM atlas is presented together with the existing M‐CRIB cortical, subcortical, and cerebellar parcellations in 10 individual neonatal MRI data sets. The novel M‐CRIB‐WM atlas, along with the M‐CRIB cortical and subcortical atlases, provide neonatal whole brain MRI coverage in the first multi‐subject manually parcellated neonatal atlas compatible with atlases commonly used at older time points. The M‐CRIB‐WM atlas is publicly available, providing a valuable tool that will help facilitate neuroimaging research into neonatal brain development in both healthy and diseased states.

Children born extremely preterm (EP; n = 12; placebo (a non-adaptive version of Cogmed), n = 9). Prior to training (baseline) and 2 weeks post-training, all children received a cognitive assessment, inclusive of immediate memory and working memory measures and an MRI. The Cogmed Improvement Index was used as a measure of improvement in trained activities in the Cogmed group. Resting-state functional MRI was used to measure training-related changes in intra- and inter-network rsfc. The networks assessed include the default mode network, the left and right central executive networks, the bilateral executive network, the dorsal attention network, and the salience network. rsfc data were compared between treatment groups and investigated in relation to changes in working memory performance. There was little evidence of differences in intra- or inter-network rsfc strength changes from baseline to post-training between treatment groups. In the Cogmed group, working memory performance was associated with increased rsfc from baseline to post-training within the precuneus network, but not in the placebo group. In the Cogmed group, results that did not survive multiple comparison correction further showed that improvement in trained activities was associated with increased rsfc between the left central and bilateral executive networks, and with decreased rsfc within the right central executive network and between the right central executive and salience networks. Changes in rsfc may facilitate working memory performance following Cogmed training. Further studies are needed to investigate how changes in rsfc are associated with behavioral changes to better support working memory in vulnerable groups.

Altered basal ganglia and thalamic connectivity may be critical for cognitive, motor and behavioural impairments common to very preterm (

Cognitive training can improve working memory in children at risk of working memory difficulties; however, response to training can vary and doubt exists if working memory improvements can be sustained long- term. This study aimed to explore whether child motivation and family environment are associated with working memory trajectories in children born extremely preterm or extremely low birth weight. Forty-five 7-year-old children completed Cogmed Working Memory Training® at home over 5–7 weeks. Children and their families completed working memory tests and child motivation and family environment questionnaires at baseline, with working memory further tested 2 weeks, 12 months and 24 months post-training. Latent growth modelling was used to explore whether child motivation and family environment factors were associated with working memory trajectories. Children’s desire for challenge, training competence, and being from a single-parent household were associated with short-term improvements in verbal short-term memory. Children from poorer functioning families were associated with short-term improvements in working memory. There was little evidence that child motivation or family environment was associated with long-term working memory changes. Child motivation and the training environment may be important for understanding training effects in children born extremely preterm or extremely low birth weight, and warrant closer examination in working memory training studies.

AIM: Brain alterations in very preterm children at risk for developmental coordination disorder were investigated. METHODS: Infants born very preterm with gestation age

The impact of very preterm (VP) birth on the development of individual basal ganglia nuclei and the thalamus during childhood remains unclear. We first aimed to compare (1a) the volumes of individual basal ganglia nuclei (nucleus accumbens, caudate nucleus, pallidum, putamen) and the thalamus at age 7 years, and (1b) their volumetric change from infancy to 7 years, in VP children with term-born children. Secondly, we aimed to (2a) determine whether basal ganglia and thalamic volumes at 7 years, or (2b) basal ganglia and thalamic growth rates from infancy to 7 years were associated with neurodevelopmental outcomes at 7 years, and whether these associations differed between the VP and term-born children. One hundred and fifty-four VP (