Cortical growth from infancy to adolescence in preterm and term-born children.

Early life experiences can exert a significant influence on cortical and cognitive development. Very preterm birth exposes infants to several adverse environmental factors during hospital admission, which affect cortical architecture. However, the subsequent consequence of very preterm birth on cortical growth from infancy to adolescence has never been defined; despite knowledge of critical periods during childhood for establishment of cortical networks. Our aims were to: chart typical longitudinal cortical development and sex differences in cortical development from birth to adolescence in healthy term-born children; estimate differences in cortical development between children born at term and very preterm; and estimate differences in cortical development between children with normal and impaired cognition in adolescence. This longitudinal cohort study included children born at term (≥37 weeks' gestation) and very preterm (<30 weeks' gestation) with MRI scans at ages 0, 7 and 13 years (n = 66 term-born participants comprising 34 with one scan, 18 with two scans and 14 with three scans; n = 201 very preterm participants comprising 56 with one scan, 88 with two scans and 57 with three scans). Cognitive assessments were performed at age 13 years. Cortical surface reconstruction and parcellation were performed with state-of-the-art, equivalent MRI analysis pipelines for all time points, resulting in longitudinal cortical volume, surface area and thickness measurements for 62 cortical regions. Developmental trajectories for each region were modelled in term-born children, contrasted between children born at term and very preterm, and contrasted between all children with normal and impaired cognition. In typically developing term-born children, we documented anticipated patterns of rapidly increasing cortical volume, area and thickness in early childhood, followed by more subtle changes in later childhood, with smaller cortical size in females than males. In contrast, children born very preterm exhibited increasingly reduced cortical volumes, relative to term-born children, particularly during ages 0-7 years in temporal cortical regions. This reduction in cortical volume in children born very preterm was largely driven by increasingly reduced cortical thickness rather than area. This resulted in amplified cortical volume and thickness reductions by age 13 years in individuals born very preterm. Alterations in cortical thickness development were found in children with impaired language and memory. This study shows that the neurobiological impact of very preterm birth on cortical growth is amplified from infancy to adolescence. These data further inform the long-lasting impact on cortical development from very preterm birth, providing broader insights into neurodevelopmental consequences of early life experiences.

Growth of prefrontal and limbic brain regions and anxiety disorders in children born very preterm.

BACKGROUND: Children born very preterm (VP) display altered growth in corticolimbic structures compared with full-term peers. Given the association between the cortiocolimbic system and anxiety, this study aimed to compare developmental trajectories of corticolimbic regions in VP children with and without anxiety diagnosis at 13 years. METHODS: MRI data from 124 VP children were used to calculate whole brain and corticolimbic region volumes at term-equivalent age (TEA), 7 and 13 years. The presence of an anxiety disorder was assessed at 13 years using a structured clinical interview. RESULTS: VP children who met criteria for an anxiety disorder at 13 years (n = 16) displayed altered trajectories for intracranial volume (ICV, p < 0.0001), total brain volume (TBV, p = 0.029), the right amygdala (p = 0.0009) and left hippocampus (p = 0.029) compared with VP children without anxiety (n = 108), with trends in the right hippocampus (p = 0.062) and left medial orbitofrontal cortex (p = 0.079). Altered trajectories predominantly reflected slower growth in early childhood (0-7 years) for ICV (ß = -0.461, p = 0.020), TBV (ß = -0.503, p = 0.021), left (ß = -0.518, p = 0.020) and right hippocampi (ß = -0.469, p = 0.020) and left medial orbitofrontal cortex (ß = -0.761, p = 0.020) and did not persist after adjusting for TBV and social risk. CONCLUSIONS: Region- and time-specific alterations in the development of the corticolimbic system in children born VP may help to explain an increase in anxiety disorders observed in this population.

Midsagittal corpus callosal thickness and cognitive impairment in Parkinson's disease.

People diagnosed with Parkinson's disease (PD) can experience significant neuropsychiatric symptoms, including cognitive impairment and dementia, the neuroanatomical substrates of which are not fully characterised. Symptoms associated with cognitive impairment and dementia in PD may relate to direct structural changes to the corpus callosum via primary white matter pathology or as a secondary outcome due to the degeneration of cortical regions. Using magnetic resonance imaging, the corpus callosum can be investigated at the midsagittal plane, where it converges to a contiguous mass and is not intertwined with other tracts. The objective of this project was thus twofold: First, we investigated possible changes in the thickness of the midsagittal callosum and cortex in patients with PD with varying levels of cognitive impairment; and secondly, we investigated the relationship between the thickness of the midsagittal corpus callosum and the thickness of the cortex. Study participants included cognitively unimpaired PD participants (n = 35), PD participants with mild cognitive impairment (n = 22), PD participants with dementia (n = 17) and healthy controls (n = 27). We found thinning of the callosum in PD-related dementia compared with PD-related mild cognitive impairment and cognitively unimpaired PD participants. Regression analyses found thickness of the left medial orbitofrontal cortex to be positively correlated with thickness of the anterior callosum in PD-related mild cognitive impairment. This study suggests that a midsagittal thickness model can uncover changes to the corpus callosum in PD-related dementia, which occur in line with changes to the cortex in this advanced disease stage.

Global transcriptomic analysis of a murine osteocytic cell line subjected to spaceflight.

Bone loss is a major health concern for astronauts during long-term spaceflight and for patients during prolonged bed rest or paralysis. Growing evidence suggests that osteocytes, the most abundant cells in the mineralized bone matrix, play a key role in sensing mechanical forces applied to the skeleton and integrating the orchestrated response into subcellular biochemical signals to modulate bone homeostasis. However, the precise molecular mechanisms underlying both mechanosensation and mechanotransduction in late-osteoblast-to-osteocyte cells under microgravity (µG) have yet to be elucidated. To unravel the mechanisms by which late osteoblasts and osteocytes sense and respond to mechanical unloading, we exposed the osteocytic cell line, Ocy454, to 2, 4, or 6 days of µG on the SpaceX Dragon-6 resupply mission to the International Space Station. Our results showed that µG impairs the differentiation of osteocytes, consistent with prior osteoblast spaceflight experiments, which resulted in the downregulation of key osteocytic genes. Importantly, we demonstrate the modulation of critical glycolysis pathways in osteocytes subjected to microgravity and discovered a set of mechanical sensitive genes that are consistently regulated in multiple cell types exposed to microgravity suggesting a common, yet to be fully elucidated, genome-wide response to microgravity. Ground-based simulated microgravity experiments utilizing the NASA rotating-wall-vessel were unable to adequately replicate the changes in microgravity exposure highlighting the importance of spaceflight missions to understand the unique environmental stress that microgravity presents to diverse cell types. In summary, our findings demonstrate that osteocytes respond to µG with an increase in glucose metabolism and oxygen consumption.

Investigating the brain structural connectome following working memory training in children born extremely preterm or extremely low birth weight.

Children born extremely preterm (EP, <28 weeks' gestation) or extremely low birth weight (ELBW, <1,000 g) are a vulnerable population at high risk of working memory impairments. We aimed to examine changes in the brain structural connectivity networks thought to underlie working memory performance, after completion of a working memory training program (Cogmed) compared with a placebo program in EP/ELBW children. This was a double-blind, placebo-controlled randomized trial (the Improving Memory in a Preterm Randomised Intervention Trial). Children born EP/ELBW received either the Cogmed or placebo program at 7 years of age (n = 91). A subset of children had magnetic resonance imaging of the brain immediately pre- and 2 weeks post-training (Cogmed n = 28; placebo n = 27). T1 -weighted and diffusion-weighted images were used to perform graph theoretical analysis of structural connectivity networks. Changes from pre-training to post-training in structural connectivity metrics were generally similar between randomized groups. There was little evidence that changes in structural connectivity metrics were related to changes in working memory performance from pre- to post-training. Overall, our results provide little evidence that the Cogmed working memory training program has training-specific effects on structural connectivity networks in EP/ELBW children.

White matter tracts related to memory and emotion in very preterm children.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. IMPACT: 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.

Long-term development of white matter fibre density and morphology up to 13 years after preterm birth: A fixel-based analysis.

BACKGROUND: It is well documented that infants born very preterm (VP) are at risk of brain injury and altered brain development in the neonatal period, however there is a lack of long-term, longitudinal studies on the effects of VP birth on white matter development over childhood. Most previous studies were based on voxel-averaged, non-fibre-specific diffusion magnetic resonance imaging (MRI) measures, such as fractional anisotropy. In contrast, the novel diffusion MRI analysis framework, fixel-based analysis (FBA), enables whole-brain analysis of microstructural and macrostructural properties of individual fibre populations at a sub-voxel level. We applied FBA to investigate the long-term implications of VP birth and associated perinatal risk factors on fibre development in childhood and adolescence. METHODS: Diffusion images were acquired for a cohort of VP (born <30 weeks' gestation) and full-term (FT, ≥37 weeks' gestation) children at two timepoints: mean (SD) 7.6 (0.2) years (n â€‹= â€‹138 VP and 32 FT children) and 13.3 (0.4) years (n â€‹= â€‹130 VP and 45 FT children). 103 VP and 21 FT children had images at both ages for longitudinal analysis. At every fixel (individual fibre population within an image voxel) across the white matter, we compared FBA metrics (fibre density (FD), cross-section (FC) and a combination of these properties (FDC)) between VP and FT groups cross-sectionally at each timepoint, and longitudinally between timepoints. We also examined associations between known perinatal risk factors and FBA metrics in the VP group. RESULTS: Compared with FT children, VP children had lower FD, FC and FDC throughout the white matter, particularly in the corpus callosum, tapetum, inferior fronto-occipital fasciculus, fornix and cingulum at ages 7 and 13 years, as well as the corticospinal tract and anterior limb of the internal capsule at age 13 years. VP children also had slower FDC development in the corpus callosum and corticospinal tract between ages 7 and 13 years compared with FT children. Within VP children, earlier gestational age at birth, lower birth weight z-score, and neonatal brain abnormalities were associated with lower FD, FC and FDC throughout the white matter at both ages. CONCLUSIONS: VP birth and concomitant perinatal risk factors are associated with fibre tract-specific alterations to axonal development in childhood and adolescence.

Working memory training and brain structure and function in extremely preterm or extremely low birth weight children.

This study in children born extremely preterm (EP; <28 weeks' gestational age) or extremely low birth weight (ELBW; <1,000 g) investigated whether adaptive working memory training using Cogmed® is associated with structural and/or functional brain changes compared with a placebo program. Ninety-one EP/ELBW children were recruited at a mean (standard deviation) age of 7.8 (0.4) years. Children were randomly allocated to Cogmed or placebo (45-min sessions, 5 days a week over 5-7 weeks). A subset had usable magnetic resonance imaging (MRI) data pretraining and 2 weeks posttraining (structural, n = 48; diffusion, n = 43; task-based functional, n = 18). Statistical analyses examined whether cortical morphometry, white matter microstructure and blood oxygenation level-dependent (BOLD) signal during an n-back working memory task changed from pretraining to posttraining in the Cogmed and placebo groups separately. Interaction analyses between time point and group were then performed. There was a significant increase in neurite density in several white matter regions from pretraining to posttraining in both the Cogmed and placebo groups. BOLD signal in the posterior cingulate and precuneus cortices during the n-back task increased from pretraining to posttraining in the Cogmed but not placebo group. Evidence for group-by-time interactions for the MRI measures was weak, suggesting that brain changes generally did not differ between Cogmed and placebo groups. Overall, while some structural and functional MRI changes between the pretraining and posttraining period in EP/ELBW children were observed, there was little evidence of training-induced neuroplasticity, with changes generally identified in both groups. Trial registration Australian New Zealand Clinical Trials Registry, anzctr.org.au; ACTRN12612000124831.

Changes in neonatal regional brain volume associated with preterm birth and perinatal factors.

BACKGROUND: Preterm birth is associated with altered brain development, with younger gestational age (GA) at birth often associated with greater brain volume reduction. Such volume alterations at term equivalent age (TEA) have been found with differing magnitude across different brain regions, although this has mostly been investigated with regards to whole tissue volumes and large-scale subdivisions. In addition to degree of prematurity, many other perinatal factors have been found to influence brain structure and development in infants born preterm. We aimed to clarify the relationships between degree of prematurity and regional brain volumes at TEA, and between perinatal factors and regional brain volumes at TEA, in finer spatial detail. METHODS: 285 preterm and term-born infants (GA at birth 24.6-42.1 weeks; 145 female; 59 born at term) were scanned at TEA. Data on perinatal factors were obtained by chart review, including sex, multiple birth, birthweight standard deviation (SD) score, postnatal growth and social risk. The Melbourne Children's Regional Infant Brain (M-CRIB) atlas was registered to the current sample, then 100 brain regions were labelled for volumetric analyses. Linear regressions with generalised estimating equations and likelihood ratio tests were performed to investigate whether GA at birth or perinatal factors were associated with regional volumes at TEA. RESULTS: Younger GA at birth was associated with smaller volumes at TEA in some regions including bilateral cerebral white matter, middle temporal gyri, amygdalae, pallidum and brainstem. In other regions, younger GA at birth was associated with larger volumes, including in primary visual, motor and somatosensory cortices. Positive associations between perinatal factors and regional volumes at TEA were found in many brain regions for birthweight SD score, and male sex, independent of GA at birth. These associations were seen on both univariable analyses, and multivariable analyses controlling for other perinatal factors. Social risk and multiple birth were generally not associated with regional brain volumes, and postnatal growth was associated with volume in many regions only after adjusting for other perinatal factors. CONCLUSIONS: These results elucidate regional brain volume differences associated with preterm birth and perinatal factors at a more detailed parcellated level than previously reported, and contribute to understanding of the complex array of correlates of preterm birth.

Brain volumetric correlates of inhibition and cognitive flexibility 16 years following childhood traumatic brain injury.

Executive functions (EFs), such as inhibition and cognitive flexibility, are essential for everyday functioning, including regulation of socially appropriate emotional responses. These skills develop during childhood and continue maturing into early adulthood. The current study aimed to investigate the very long-term impact of childhood traumatic brain injury (TBI) on inhibition and cognitive flexibility, and to examine whether global white matter is associated with these abilities. Twenty-eight young adult survivors of childhood TBI (mean age at 16-year follow-up = 21.67 years, SD = 2.70) and 16 typically developing controls (TDCs), group-matched for age, sex, and socioeconomic status, completed tests of inhibition and cognitive flexibility and underwent structural MRI. Survivors of childhood TBI did not significantly differ from TDCs on EF or white matter volume. However, the relationship between EF and white matter volume differed between survivors of TBI and TDCs. Survivors of TBI did not mimic the brain behavior relationship that characterized EF in TDCs. The inverse brain behavior relationship, exhibited by childhood TBI survivors, suggests disruptions in the whole brain underpinning EF following childhood TBI.

A new neonatal cortical and subcortical brain atlas: the Melbourne Children's Regional Infant Brain (M-CRIB) atlas.

Investigating neonatal brain structure and function can offer valuable insights into behaviour and cognition in healthy and clinical populations; both at term age, and longitudinally in comparison with later time points. Parcellated brain atlases for adult populations are readily available, however warping infant data to adult template space is not ideal due to morphological and tissue differences between these groups. Several parcellated neonatal atlases have been developed, although there remains strong demand for manually parcellated ground truth data with detailed cortical definition. Additionally, compatibility with existing adult atlases is favourable for use in longitudinal investigations. We aimed to address these needs by replicating the widely-used Desikan-Killiany (2006) adult cortical atlas in neonates. We also aimed to extend brain coverage by complementing this cortical scheme with basal ganglia, thalamus, cerebellum and other subcortical segmentations. Thus, we have manually parcellated these areas volumetrically using high-resolution neonatal T2-weighted MRI scans, and initial automated and manually edited tissue classification, providing 100 regions in all. Linear and nonlinear T2-weighted structural templates were also generated. In this paper we provide manual parcellation protocols, and present the parcellated probability maps and structural templates together as the Melbourne Children's Regional Infant Brain (M-CRIB) atlas.

Regional brain morphometric characteristics of nonsyndromic cleft lip and palate.

Nonsyndromic cleft lip and palate (NSCLP) encompasses a group of orofacial abnormalities. Emerging evidence has revealed the presence of structural brain abnormalities in affected individuals. Previous studies have performed structure-based volumetric analysis of the brain assessing gross lobular subdivisions of the cerebral cortex and white matter which may have only vague relationships to the functional subregions implicated in behavioral and cognitive deficits observed in NSCLP patients. High-resolution magnetic resonance imaging structural data were acquired to provide a detailed characterization of the brain with respect to both regional cortical volume and thickness in 26 children with NSCLP and 26 age- and demographically matched typically developing children. Children with NSCLP exhibited abnormally large cerebral cortex grey matter volumes with decreased volumes of subcortical grey matter and cerebral white matter structures. Hemisphere-specific patterns of cortical volume and thickness abnormalities were identified. This study is the first to examine cortical thickness abnormalities in NSCLP. Overall, these findings suggest that the brains of children with NSCLP are less mature than those of their age-matched peers. Gender-specific comparisons reveal that NSCLP females were more immature compared to their typically developing peers compared to NSCLP males.

Updates to the Melbourne Children's Regional Infant Brain Software Package (M-CRIB-S).

The delineation of cortical areas on magnetic resonance images (MRI) is important for understanding the complexities of the developing human brain. The previous version of the Melbourne Children's Regional Infant Brain (M-CRIB-S) (Adamson et al. Scientific Reports, 10(1), 10, 2020) is a software package that performs whole-brain segmentation, cortical surface extraction and parcellation of the neonatal brain. Available cortical parcellation schemes in the M-CRIB-S are the adult-compatible 34- and 31-region per hemisphere Desikan-Killiany (DK) and Desikan-Killiany-Tourville (DKT), respectively. We present a major update to the software package which achieves two aims: 1) to make the voxel-based segmentation outputs derived from the Freesurfer-compatible M-CRIB scheme, and 2) to improve the accuracy of whole-brain segmentation and cortical surface extraction. Cortical surface extraction has been improved with additional steps to improve penetration of the inner surface into thin gyri. The improved cortical surface extraction is shown to increase the robustness of measures such as surface area, cortical thickness, and cortical volume.

Diffusion tensor imaging detects white matter abnormalities and associated cognitive deficits in chronic adolescent TBI.

PRIMARY OBJECTIVE: This study examined long-term alterations in white matter microstructure following TBI in adolescence using diffusion tensor imaging (DTI). It was hypothesized that white matter integrity would be compromised in adolescents with TBI and would correlate with measures of executive functioning and cognitive abilities. RESEARCH DESIGN: This study employed whole-brain, voxel-wise, statistical comparison of DTI indices in youth of 12-17 years old (mean = 15.06) with TBI vs an age- and gender-matched cohort (mean age = 15.37). METHODS AND PROCEDURES: This study scanned 17 adolescents with complicated-mild-to-severe TBI, 1-3 years after injury, and 13 healthy adolescents. Tract-Based Spatial Statistics (TBSS) was employed for DTI analysis. MAIN OUTCOMES AND RESULTS: Overall diffusivity elevations were found in the TBI group with increases in axial diffusivity in the right hemisphere. White matter integrity was associated with word reading, planning and processing times in the TBI group, but not healthy controls. CONCLUSIONS: The detected abnormalities in axial diffusivity may reflect neuronal regeneration and cerebral reorganization after injury. These findings provide tentative evidence of persistent white matter alteration following TBI in adolescence. Associations of DTI indices with cognitive performance following TBI provide tentative support for links between white matter integrity and performance post-TBI.

Parcellation of the neonatal cortex using Surface-based Melbourne Children's Regional Infant Brain atlases (M-CRIB-S).

Longitudinal studies measuring changes in cortical morphology over time are best facilitated by parcellation schemes compatible across all life stages. The Melbourne Children's Regional Infant Brain (M-CRIB) and M-CRIB 2.0 atlases provide voxel-based parcellations of the cerebral cortex compatible with the Desikan-Killiany (DK) and the Desikan-Killiany-Tourville (DKT) cortical labelling schemes. This study introduces surface-based versions of the M-CRIB and M-CRIB 2.0 atlases, termed M-CRIB-S(DK) and M-CRIB-S(DKT), with a pipeline for automated parcellation utilizing FreeSurfer and developing Human Connectome Project (dHCP) tools. Using T2-weighted magnetic resonance images of healthy neonates (n = 58), we created average spherical templates of cortical curvature and sulcal depth. Manually labelled regions in a subset (n = 10) were encoded into the spherical template space to construct M-CRIB-S(DK) and M-CRIB-S(DKT) atlases. Labelling accuracy was assessed using Dice overlap and boundary discrepancy measures with leave-one-out cross-validation. Cross-validated labelling accuracy was high for both atlases (average regional Dice = 0.79-0.83). Worst-case boundary discrepancy instances ranged from 9.96-10.22 mm, which appeared to be driven by variability in anatomy for some cases. The M-CRIB-S atlas data and automatic pipeline allow extraction of neonatal cortical surfaces labelled according to the DK or DKT parcellation schemes.

Tracking regional brain growth up to age 13 in children born term and very preterm.

Serial regional brain growth from the newborn period to adolescence has not been described. Here, we measured regional brain growth in 216 very preterm (VP) and 45 full-term (FT) children. Brain MRI was performed at term-equivalent age, 7 and 13 years in 82 regions. Brain volumes increased between term-equivalent and 7 years, with faster growth in the FT than VP group. Perinatal brain abnormality was associated with less increase in brain volume between term-equivalent and 7 years in the VP group. Between 7 and 13 years, volumes were relatively stable, with some subcortical and cortical regions increasing while others reduced. Notably, VP infants continued to lag, with overall brain size generally less than that of FT peers at 13 years. Parieto-frontal growth, mainly between 7 and 13 years in FT children, was associated with higher intelligence at 13 years. This study improves understanding of typical and atypical regional brain growth.

Anterior cingulate cortex abnormalities associated with a first psychotic episode in bipolar disorder.

BACKGROUND: The anterior cingulate cortex is frequently implicated in the pathophysiology of bipolar disorder, but magnetic resonance imaging (MRI) studies have reported variable findings owing to a reliance on patient samples with chronic illness and to limited appreciation of the region's heterogeneity. AIMS: To characterise anterior cingulate cortex abnormalities in patients with bipolar disorder experiencing their first episode of psychosis while accounting for regional anatomical variability. METHOD: Grey matter volume, surface area and cortical thickness were measured in six anterior cingulate cortex subregions per hemisphere using MRI scans acquired from 26 patients with bipolar I disorder experiencing first-episode psychosis and 26 healthy controls matched for age, gender and regional morphological variability. RESULTS: Relative to controls, male patients displayed increased thickness in the right subcallosal limbic anterior cingulate cortex. No significant differences were identified in females for grey matter volume or surface area measures. The findings were not attributable to medication effects. CONCLUSIONS: These data suggest that first-episode psychosis in bipolar disorder is associated with a gender-specific, right-lateralised thickness increase in anterior cingulate cortex subregions known to play a role in regulating physiological stress responses.

Quantifying individual differences in brain morphometry underlying symptom severity in Autism Spectrum Disorders.

The neurobiology of heterogeneous neurodevelopmental disorders such as autism spectrum disorders (ASD) are still unclear. Despite extensive efforts, most findings are difficult to reproduce due to high levels of individual variance in phenotypic expression. To quantify individual differences in brain morphometry in ASD, we implemented a novel subject-level, distance-based method on subject-specific attributes. In a large multi-cohort sample, each subject with ASD (n = 100; n = 84 males; mean age: 11.43 years; mean IQ: 110.58) was strictly matched to a control participant (n = 100; n = 84 males; mean age: 11.43 years; mean IQ: 110.70). Intrapair Euclidean distance of MRI brain morphometry and symptom severity measures (Social Responsiveness Scale) were entered into a regularised machine learning pipeline for feature selection, with rigorous out-of-sample validation and permutation testing. Subject-specific structural morphometry features significantly predicted individual variation in ASD symptom severity (19 cortical thickness features, p = 0.01, n = 5000 permutations; 10 surface area features, p = 0.006, n = 5000 permutations). Findings remained robust across subjects and were replicated in validation samples. Identified cortical regions implicate key hubs of the salience and default mode networks as neuroanatomical features of social impairment in ASD. Present results highlight the importance of subject-level markers in ASD, and offer an important step forward in understanding the neurobiology of heterogeneous disorders.

Efficiency of structural connectivity networks relates to intrinsic motivation in children born extremely preterm.

Intrinsic motivation is essential for academic success and cognitive growth, but limited work has examined the neuroanatomical underpinnings of intrinsic motivation from a network perspective, particularly in early childhood. Using graph theoretical analysis, this study investigated global and local properties of structural connectivity networks in relation to intrinsic motivation within a vulnerable group of children at early school age. Fifty-three 7 year-old children born extremely preterm (<28 weeks' gestational age)/extremely low birth weight (<1000 g) underwent T1 and diffusion weighted imaging. Structural connectivity networks were generated using 162 cortical and subcortical nodes, and edges were created using constrained spherical deconvolution-based tractography. Global and node-specific network measures were analyzed in association with self-reported aspects of intrinsic motivation for school learning (Mastery, Challenge and Curiosity) using linear regression. Results indicated that increased information transfer across the network was associated with greater Mastery, while increased clustering and small-world topology related to greater Challenge. Increased efficiency and connection strength of the striatum in particular, related to greater intrinsic motivation. These findings suggest that both integrated and segregated network communication support aspects of intrinsic motivation in childhood, and shed new light on structural network properties important for intrinsic motivation orientations in extremely preterm children at early school age.

Desikan-Killiany-Tourville Atlas Compatible Version of M-CRIB Neonatal Parcellated Whole Brain Atlas: The M-CRIB 2.0.

Our recently published M-CRIB atlas comprises 100 neonatal brain regions including 68 compatible with the widely-used Desikan-Killiany adult cortical atlas. A successor to the Desikan-Killiany atlas is the Desikan-Killiany-Tourville atlas, in which some regions with unclear boundaries were removed, and many existing boundaries were revised to conform to clearer landmarks in sulcal fundi. Our first aim here was to modify cortical M-CRIB regions to comply with the Desikan-Killiany-Tourville protocol, in order to offer: (a) compatibility with this adult cortical atlas, (b) greater labeling accuracy due to clearer landmarks, and (c) optimisation of cortical regions for integration with surface-based infant parcellation pipelines. Secondly, we aimed to update subcortical regions in order to offer greater compatibility with subcortical segmentations produced in FreeSurfer. Data utilized were the T2-weighted MRI scans in our M-CRIB atlas, for 10 healthy neonates (post-menstrual age at MRI 40-43 weeks, four female), and corresponding parcellated images. Edits were performed on the parcellated images in volume space using ITK-SNAP. Cortical updates included deletion of frontal and temporal poles and 'Banks STS,' and modification of boundaries of many other regions. Changes to subcortical regions included the addition of 'ventral diencephalon,' and deletion of 'subcortical matter' labels. A detailed updated parcellation protocol was produced. The resulting whole-brain M-CRIB 2.0 atlas comprises 94 regions altogether. This atlas provides comparability with adult Desikan-Killiany-Tourville-labeled cortical data and FreeSurfer-labeed subcortical data, and is more readily adaptable for incorporation into surface-based neonatal parcellation pipelines. As such, it offers the ability to help facilitate a broad range of investigations into brain structure and function both at the neonatal time point and developmentally across the lifespan.