Biology subjects

Nosarti, C.

Publications and source records attributed to Nosarti, C..

At least 19 recordsLinked to original sources

bioRxiv2026

Development of Neonatal Functional Brain Network Organisation and Its Association with Childhood Neurodevelopmental Outcomes

The human brain undergoes rapid dynamic changes in the neonatal period that are essential for later cognitive and behavioural performance. Using resting-state fMRI data from 394 neonates (325 term-born, 69 preterm-born) within the first month after birth, we characterised the early development of functional network organisation, the effects of preterm birth, and the association between neonatal functional organisation and later neurodevelopmental outcomes in infancy (18 months) and childhood (4-6 years). We found increased functional integration and segregation across a wide range of functional sub-networks and increased mean functional connectivity strength (mean FCS) within the subcortical and cerebellar regions with increasing PMA at scan. Compared with term-born neonates, preterm-born neonates showed significantly lower mean FCS, functional integration and segregation globally. We further showed that whilst neonatal functional brain network organisation was not associated with neurodevelopmental outcomes measured during infancy (18 months), it was associated with later neurodevelopmental outcomes in early childhood (4-6 years). Specifically, higher functional integration and segregation at birth were linked with lower SDQ total difficulties score at 4-6 years. Our findings suggest that neonatal functional brain organisation reflects not only transient developmental processes, but also stable individual differences that provide insight into neurodevelopmental outcomes in later childhood.

neuroscience↗

bioRxiv2026

Psychotic-like experiences in children born very preterm: evidence from clinical and population-based cohorts

Background and aimVery preterm birth (VPT; [≤]32 weeks gestation) is associated with an increased risk of later psychiatric disorders, including psychosis. Although psychosis typically emerges in adulthood, subclinical early signs along the psychosis continuum, such as psychotic-like experiences (PLEs), can be observed much earlier. We therefore aimed to study PLEs in childhood in VPT individuals recruited from a clinical cohort compared with full-term (FT) controls. We subsequently investigated whether findings could be replicated in an independent population-based cohort. MethodsPrimary analyses were conducted in the Brain, Immunity and Psychopathology (BIPP) study, including 197 children born VPT recruited through Neonatal Intensive Care Units and 72 FT controls assessed at a mean age of 10.50{+/-}1.77 years. Between-group differences in PLEs were then examined in the Adolescent Brain Cognitive Development (ABCD) study, including 149 children born VPT and 9519 FT controls assessed at a mean age of 9.94 {+/-} 0.63 years. PLEs were assessed using the Prodromal Questionnaire-Brief Child Version (PQ-BC), yielding frequency and distress-related scores for both the total scale and three specific domains (unusual thought content, perceptual abnormalities, disorganised speech). Regression models tested associations between birth status (VPT and control) and PQ-BC scores adjusting for age, sex, and socio-economic status, with secondary models additionally adjusting for cognitive ability and broader psychopathology. Pooled analyses examined cohort effects (BIPP and ABCD) and cohort-by-group status (VPT and control) interactions. ResultsIn BIPP, VPT birth was associated with higher PQ-BC total ({beta}=1.61, p=0.004) and distress scores ({beta}=0.78, p=0.039), with the strongest and most consistent associations observed for perceptual abnormalities across total score (sum of endorsed items), distressing items, and distress severity scores (all p[≤]0.01). These associations were attenuated but largely persisted after adjustment for cognitive ability and broader psychopathology, particularly for perceptual abnormalities. In ABCD, VPT birth was not significantly associated with global or domain-specific PQ-BC outcomes. DiscussionVPT birth is associated with increased vulnerability to PLEs in childhood, particularly in the domain of perceptual abnormalities. The lack of clear replication in the population-based ABCD cohort may reflect differences in the composition of its VPT subgroup, which may not fully represent VPT individuals typically seen in clinical cohorts.

developmental biology↗

bioRxiv2025

A cortical signature of very preterm birth across development and its association with neurodevelopmental outcomes

Gestational age plays a crucial role in neurodevelopment, and individuals born very preterm (VPT; <32 weeks gestation) are at elevated risk for cognitive, behavioural and psychiatric problems across the lifespan. Better understanding of the impact of very preterm birth on cortical maturation trajectories could inform mechanistic insights into the origins of these sequelae. Here we compared cortical morphology between VPT individuals and full-term controls in three datasets spanning birth, childhood and adulthood. We identified a consistent cortical signature of VPT birth, characterized by reduced surface area and cortical folding in the frontal, temporal, parietal and insular regions, which persisted across development. Furthermore, in two large infant cohorts, we found that this cortical signature was significantly associated with neonatal clinical factors and with poorer motor outcomes at follow-up, suggesting its potential as a neuroimaging marker for long-term neurodevelopmental risk. Given that early motor development plays a key role in shaping infants interactions with the environment and supporting later cognitive and behavioural development, our findings provide insights into the neurobiological pathways linking VPT birth to subsequent neurodevelopmental difficulties.

neuroscience↗

bioRxiv2025

In vivo tractography of human neonatal white-matter pathways underlying hypothalamic and reward functions to study predispositions to neurodevelopmental conditions and obesity

White matter (WM) tracts of the reward, limbic, and autonomic systems implicate the hypothalamus, nucleus accumbens, ventral tegmental area and the amygdala and are associated with autism, ADHD, addiction and obesity. However, since most of these structures remain uncharacterised in vivo in human neonates, research on the early-life predispositions to these long-term "mind and body" conditions and the impact of common fetal exposures such as maternal obesity remains limited. Through the developing human connectome project, we acquired 3T brain diffusion and structural magnetic resonance imaging from healthy neonates born at-term to 137 normal-weight women (controls) and to 28 obese women and scanned at mean 40 weeks+6 days (+/-9 days) postmenstrual age (PMA). We first developed novel tractography protocols to reconstruct anatomical WM pathways for the neonatal medial forebrain bundle, ventral amygdalofugal pathway, amygdalo-accumbens fasciculus, stria terminalis and autonomic dorsal longitudinal fasciculus (DLF). We then quantified WM structure from the mean tract fibre bundle density (FD) and fibre cross-section (FC) and using regression path models evaluated WM change across PMA and the effects of antenatal obesity exposure and neonatal covariates. Lastly, we explored if neonatal WM FD and obesity exposure predicted child psycho-cognitive outcomes and anthropometry at 18 months. We show successful in vivo tractography of tracts with high topographical correspondence to adult histology, including in subcompartments of the hypothalamus and amygdala. The obesity exposure*PMA interaction was significant for mean FD in the bilateral amygdalo-accumbens fasciculus and right uncinate fasciculus. Males had larger FC in these same tracts bilaterally. Antenatal obesity exposure predicted lower cognitive scores and higher WHO weight and height z-scores at 18 months. Toddler reward-seeking temperament was correlated with higher weight zscore and was predicted by higher neonatal FD of the amygdalo-accumbens and uncinate fasciculi. Denser neonatal DLF predicted higher language and cognitive scores and fewer autistic traits at 18 months. In conclusion, we inform on neuroanatomical growth in vivo of discrete multisystemic regulatory networks and present evidence for early-life predispositions to psychological outcomes and obesity.

neuroscience↗

bioRxiv2024

Verifying the concordance between motion corrected and conventional MPRAGE for pediatric morphometric analysis

PurposeTo validate a retrospective motion correction technique, Distributed and Incoherent Sample Orders for Reconstruction Deblurring using Encoding Redundancy (DISORDER), for pediatric brain morphometry. MethodsTwo T1-weighted MPRAGE 3D datasets were acquired at 3T in thirty-seven children, median age 7.75 years; one with conventional linear phase encoding and one using DISORDER. MPRAGE images were scored as motion-free or motion-corrupt. Cortical morphometry and regional brain volumes were measured with FreeSurfer, subcortical grey matter (GM) with FSL-FIRST, and hippocampal volumes with HippUnfold. Intraclass correlation coefficient (ICC) was used to determine agreement between the 2 MPRAGE acquisitions. Mann-Whitney U was used to test the difference between measures obtained using DISORDER and (i) motion-free and (ii) motion-corrupt conventional MPRAGE data. ResultsICC measures were good/excellent for most subcortical GM (motion-free, 0.75-0.96; motion-corrupt, 0.62-0.98) and regional brain volumes (motion-free 0.47-0.99; motion-corrupt, 0.54-0.99) between conventional MPRAGE and DISORDER data, except for the amygdala and nucleus accumbens (motion-free, 0.38-0.65; motion- corrupt, 0.1-0.42). However, these values were less consistent for motion-corrupt conventional MPRAGE data for hippocampal volumes (motion-free 0.65-0.99; motion-corrupt, 0.11-0.91) and cortical measures (motion-free 0.76-0.98; motion- corrupt, 0.09-0.74). Mann-Whitney U showed percentage differences in measures obtained with motion-corrupt conventional MPRAGE compared to DISORDER data were significantly greater than in those obtained using motion-free conventional MPRAGE data in 22/58 structures. ConclusionIn the absence of motion, morphometric measures obtained using DISORDER are largely consistent with those from conventional MPRAGE data, whereas improved reliability is obtained by DISORDER for motion-degraded scans. This study validates DISORDER for brain morphometric studies in children.

neuroscience↗

bioRxiv2024

Exploring functional connectivity in clinical and data-driven groups of preterm and term adults

BackgroundAdults born very preterm (i.e., at <33 weeks gestation) are more susceptible to long-lasting structural and functional brain alterations and cognitive and socio-emotional difficulties, compared to full-term controls. However, behavioural heterogeneity within very preterm and full-term individuals makes it challenging to find biomarkers of specific outcomes. To address these questions, we parsed brain-behaviour heterogeneity in participants subdivided according to their clinical birth status (very preterm vs full-term) and/or data-driven behavioural phenotype (regardless of birth status). MethodsThe Network Based Statistic approach was used to identify topological components of resting state functional connectivity differentiating between i) 116 very preterm and 83 full-term adults (43% and 57% female, respectively), and ii) data-driven behavioural subgroups identified using consensus clustering (n= 156, 46% female). Age, sex, socio-economic status, and in-scanner head motion were used as confounders in all analyses. Post-hoc two-way group interactions between clinical birth status and behavioural data-driven subgrouping classification labels explored whether functional connectivity differences between very preterm and full-term adults varied according to distinct behavioural outcomes. ResultsVery preterm compared to full-term adults had poorer scores in selective measures of cognitive and socio-emotional processing and displayed complex patterns of hyper- and hypo-connectivity in subsections of the default mode, visual, and ventral attention networks. Stratifying the study participants in terms of their behavioural profiles (irrespective of birth status), identified two data-driven subgroups: An "At-risk" subgroup, characterised by increased cognitive, mental health, and socio-emotional difficulties, displaying hypo-connectivity anchored in frontal opercular and insular regions, relative to a "Resilient" subgroup with more favourable outcomes. No significant interaction was noted between clinical birth status and behavioural data-driven subgrouping classification labels in terms of functional connectivity. ConclusionsFunctional connectivity differentiating between very preterm and full-term adults was dissimilar to functional connectivity differentiating between the data-driven behavioural subgroups. We speculate that functional connectivity alterations observed in very preterm relative to full-term adults may confer both risk and resilience to developing behavioural sequelae associated with very preterm birth, while the localised functional connectivity alterations seen in the "At-risk" subgroup relative to the "Resilient" subgroup may underlie less favourable behavioural outcomes in adulthood, irrespective of birth status.

developmental biology↗

bioRxiv2023

Objective assessment of visual attention in toddlerhood

Visual attention is an important mechanism through which children learn about their environment, and individual differences could substantially shape later development. Eyetracking provides a sensitive and scalable tool for assessing visual attention that has potential for objective assessment of child development, but to date the majority of studies are small and replication attempts are rare. This study investigates the feasibility of a comprehensive eye-tracking assessment of visual attention and introduces a shared data resource for the scientific community. Data from eight eyetracking tasks were collected from 350 term-born (166 females) 18-month-olds recruited as neonates http://www.developingconnectome.org/). Analyses showed expected condition effects for seven of eight tasks (p-values from <.001 to .04), an important indication of replicability. Consistent with some theoretical models of visual attention, structural equation modelling indicated participants performance could be explained by two factors representing social and non-social attention. Comprehensive eye-tracking batteries can objectively measure individual differences in core components of visual attention in large-scale toddlerhood studies. This is the first large-scale comprehensive study to present high-quality normative eye-tracking data from a large task battery in toddlers and make them freely available to the scientific community.

neuroscience↗

bioRxiv2022

Exploring cognitive, behavioural and autism trait network topology in very preterm and term-born children

Compared to full-term (FT) born peers, children who were born very preterm (VPT; <32 weeks gestation) are likely to display more cognitive and behavioural difficulties, including inattention, anxiety and socio-communication problems. In the published literature, such difficulties tend to be studied independently, thus failing to account for how different aspects of child development interact. The current study aimed to investigate childrens cognitive and behavioural outcomes as interconnected, dynamically related facets of development that influence one another. Participants were 93 VPT and 55 FT children (median age 8.79 years). IQ was evaluated with the Wechsler Intelligence Scale for Children - 4th edition (WISC-IV), autism spectrum condition (ASC) traits with the Social Responsiveness Scale - 2nd edition (SRS-2), behavioural and emotional problems with the Strengths and Difficulties Questionnaire (SDQ), temperament with the Temperament in Middle Childhood Questionnaire (TMCQ) and executive function with the Behaviour Rating Inventory of Executive Functioning (BRIEF-2). Outcome measures were studied in VPT and FT children using Network Analysis, a method that graphically represents partial correlations between variables and yields information on each variables propensity to form a bridge between other variables. Results showed that VPT and FT children exhibited marked topological differences. Bridges (i.e., the variables most connected to others) in the VPT group network were: SDQ Conduct Problems scale and BRIEF-2 Organisation of Materials scale. In the FT group network, the most important bridges were: the BRIEF-2 Initiate, SDQ Emotional Problems and SDQ Prosocial Behaviours scales. These findings highlight the importance of targeting different aspects of development to support VPT and FT children in person-based interventions.

developmental biology↗

bioRxiv2022

Fractions strategy differences in those born extremely preterm

IntroductionTo investigate the effects of different strategies and cognitive load we explored brain hemodynamic responses associated with the use of different strategies to solve subtraction of fractions. We focused on those born extremely preterm (EPT; <28 weeks gestation) as they are known to have cognitive challenges and struggle with mathematics. We also included a group of full-term (FT) peers for comparison. MethodsFunctional MRI was acquired while the participants mentally solved fraction equations using either a strategy based on improper or mixed fractions. Different fraction item types were given, which affected respective required cognitive loads per strategy. Diffusion and T1-weighted structural images were also acquired. ResultsThe EPT and FT groups differed in terms of task-related hemodynamic responses. Functional group differences were greatest when strategies were applied to item types that result in high cognitive load. Other findings showed reduced white and grey matter volume and reduced white matter connectivity in widespread areas in the EPT group compared to the FT group. ConclusionThe understanding of function and structure presented here may help inform pedagogical practices by allowing for tailoring of mathematical education through identifying suitable strategy adoption that depends on item type, to circumvent weaknesses in cognitive skills.

neuroscience↗

bioRxiv2022

Neonatal brain dynamic functional connectivity: impact of preterm birth and association with early childhood neurodevelopment

Brain dynamic functional connectivity characterises transient connections between brain regions, changing over time. Features of brain dynamics have been linked to emotion and cognition in adult individuals, and atypical patterns have been associated with neurodevelopmental conditions such as autism. Although reliable functional brain networks have been consistently identified in neonates, little is known about the early development of dynamic functional connectivity. In this study we characterise dynamic functional connectivity with functional magnetic resonance imaging (fMRI) in the first few weeks of postnatal life in term-born (n = 324) and preterm-born (n = 66) individuals. We show that a dynamic landscape of brain connectivity is already established by the time of birth in the human brain, characterised by six transient states of neonatal functional connectivity with changing dynamics through the neonatal period. The pattern of dynamic connectivity is atypical in preterm-born infants, and associated with atypical social, sensory, and repetitive behaviours measured by the Quantitative Checklist for Autism in Toddlers (Q-CHAT) scores at 18 months of age.

neuroscience↗

bioRxiv2022

Parsing brain-behavior heterogeneity in very preterm born children using integrated similarity networks

Very preterm birth (VPT; [≤] 32 weeks gestation) is associated with altered brain development and cognitive and behavioral difficulties across the lifespan. However, heterogeneity in outcomes among individuals born VPT makes it challenging to identify those most vulnerable to neurodevelopmental sequelae. Here, we aimed to stratify VPT children into distinct behavioral subgroups and explore between-subgroup differences in neonatal brain structure and function. 198 VPT children (98 females) previously enrolled in the Evaluation of Preterm Imaging study (EudraCT 2009-011602-42) underwent Magnetic Resonance Imaging at term-equivalent age and neuropsychological assessments at 4-7 years. Using an integrative clustering approach, we combined neonatal socio-demographic, clinical factors and childhood socio-emotional and executive function outcomes, to identify distinct subgroups of children based on their similarity profiles in a multidimensional space. We characterized resultant subgroups using domain-specific outcomes (temperament, psychopathology, IQ and cognitively stimulating home environment) and explored between-subgroup differences in neonatal brain volumes (voxel-wise Tensor-Based-Morphometry), functional connectivity (voxel-wise degree centrality) and structural connectivity (Tract-Based-Spatial-Statistics). Results showed two-and three-cluster data-driven solutions. The two-cluster solution comprised a resilient subgroup (lower psychopathology and higher IQ, executive function and socio-emotional outcomes) and an at-risk subgroup (poorer behavioral and cognitive outcomes). The three-cluster solution showed an additional third intermediate subgroup displaying behavioral and cognitive outcomes intermediate between the resilient and at-risk subgroups. The resilient subgroup had the most cognitively stimulating home environment and the at-risk subgroup showed the highest neonatal clinical risk, while the intermediate subgroup showed the lowest clinical but the highest socio-demographic risk. Compared to the intermediate subgroup, the resilient subgroup displayed larger neonatal insular and orbitofrontal volumes and stronger orbitofrontal functional connectivity, while the at-risk group showed widespread white matter microstructural alterations. These findings suggest that risk stratification following VPT birth is feasible and could be used translationally to guide personalized interventions aimed at promoting childrens resilience.

neuroscience↗

bioRxiv2022

Clinical, socio-demographic, and parental correlates of early autism traits

BackgroundAutism traits emerge between the ages of 1 and 2. It is not known if experiences which increase the likelihood of childhood autism are related to early trait emergence, or if other exposures are more important. Identifying factors linked to toddler autism traits in the general population may improve our understanding of the mechanisms underlying atypical neurodevelopment. MethodsClinical, socio-demographic, and parental information was collected at birth from 536 toddlers in London, UK (gestational age at birth, sex, maternal body mass index, age, parental education level, parental first language, parental history of neurodevelopmental disorders) and at 18 months (parent cohabiting status, two measures of social deprivation, three measures of maternal parenting style, and a measure of maternal postnatal depression). General neurodevelopment was assessed with the Bayley Scales of Infant and Toddler Development, 3rd Edition (BSID-III), and autism traits were assessed using the Quantitative Checklist for Autism in Toddlers (Q-CHAT). Multivariable models were used to identify associations between variables and Q-CHAT. A model including BSID-III was used to identify factors associated with Q-CHAT independent of general neurodevelopment. Models were also evaluated addressing variable collinearity with principal component analysis (PCA). ResultsA multivariable model explained 20% of Q-CHAT variance, with four individually significant variables (two measures of parenting style and two measures of socio-economic deprivation). After adding general neurodevelopment into the model 36% of Q-CHAT variance was explained, with three individually significant variables (two measures of parenting style and one measure of language development). After addressing variable collinearity with PCA, parenting style and social deprivation were positively correlated with Q-CHAT score via a single principal component, independently of general neurodevelopment. Neither sex nor family history of autism were associated with Q-CHAT score. LimitationsThe Q-CHAT is parent rated and is therefore a subjective opinion rather than a clinical assessment. We measured Q-CHAT at a single timepoint, and to date no participant has been followed up in later childhood, so we are focused purely on emerging traits rather than clinical autism diagnoses. ConclusionsAutism traits are common at age 18 months, and greater emergence is specifically related to exposure to early life adversity.

neuroscience↗

bioRxiv2022

Development of neonatal brain functional centrality and alterations associated with preterm birth

Formation of the functional connectome in early life underpins future learning and behaviour. However, our understanding of how the functional organisation of brain regions into interconnected hubs (centrality) matures in the early postnatal period is limited, especially in response to factors associated with adverse neurodevelopmental outcomes such as preterm birth. We characterised voxel-wise functional centrality (weighted degree) in 366 neonates from the Developing Human Connectome Project. We tested the hypothesis that functional centrality matures with age at scan in term-born babies and is disrupted by preterm birth. Finally, we asked whether neonatal functional centrality predicts general neurodevelopmental outcomes at 18 months. We report an age-related increase in functional centrality predominantly within visual regions and decrease within motor and auditory regions in term-born infants. Preterm-born infants scanned at term equivalent age had higher functional centrality predominantly within visual regions and lower measures in motor regions. Functional centrality was not related to outcome at 18 months old. Thus, preterm birth appears to affect functional centrality in regions undergoing substantial development during the perinatal period. Our work raises the question of whether these alterations are adaptive or disruptive, and whether they predict neurodevelopmental characteristics that are more subtle or emerge later in life.

neuroscience↗

bioRxiv2022

Digital data repository and automatic analysis framework for FDOPA PET neuroimaging

IntroductionFDOPA PET has been used extensively to image the human brain in many clinical disorders and has the potential to be used for patient stratification and individualized treatment. However, to reach its full and effective clinical translation, FDOPA PET requires both a robust data infrastructure and analytical protocol that are capable of ensuring high quality data and metadata, accurate biological quantification, and replicable results. In this study we evaluate a digital data repository and automated analytical framework for FDOPA PET neuroimaging that can produce an individualised quantification of dopamine synthesis capacity in the living human brain. MethodsThe imaging platform XNAT was used to store the Kings College London institutional brain FDOPA PET imaging archive, alongside individual demographics and clinical information. A fully automated analysis pipeline for imaging processing and data quantification was developed in Python and integrated in XNAT using the Docker technology. Reproducibility was assessed in test-retest datasets both in controls and patients with psychosis. The agreement between the automated analysis estimates and the results derived by the manual analysis were compared. Finally, using a sample of healthy controls (N=115), a sensitivity analysis was performed to explore the impact of experimental and demographic variables on the FDOPA PET measures. ResultsThe final data repository includes 892 FDOPA PET scans organized from 23 different studies, collected at five different imaging sites. After removing commercials studies, the infrastructure consisted of 792 FDOPA PET scans from 666 individuals (female 33.9%, healthy controls 29.1%) collected from four different imaging sites between 2004-2021. The automated analysis pipeline provided results that were in agreement with the results from the manual analysis, with a Pearsons correlation that ranged from 0.64 to 0.99 for Kicer, and from 0.79 to 1.00 for SUVR. The mean absolute difference between the two pipelines ranges from 3.4% to 9.4% for Kicer, and from 2.5% to 12.4% for SUVR. Moreover, we found good reproducibility of the data analysis by the automated pipeline (in the whole striatum for the Kicer: ICC for the controls = 0.71, ICC for the psychotic patients = 0.88). From the demographic and experimental variables assessed, gender was found to most influence striatal dopamine synthesis capacity (F = 10.7, p <0.001), with women showing greater dopamine synthesis capacity than men, while the effects of weight, age, injected radioactivity, and scanner, varied by brain region and parameter of interest. ConclusionsCombining information from different neuroimaging studies has allowed us to test comprehensively the automated pipeline for quantification of dopamine synthesis capacity using FDOPA PET data and to validate its replicability and reproducibility performances on a large sample size. This validation process is a necessary methodological step for the development of the clinical application of FDOPA PET as precision medicine biomarker. The proposed infrastructure is generalisable behind the FDOPA radiotracer.

bioengineering↗

bioRxiv2021

Neonatal multi-modal cortical profiles predict 18-month developmental outcomes

Developmental delays in infanthood often persist, turning into life-long difficulties, and coming at great cost for the individual and community. By examining the developing brain and its relation to developmental outcomes we can start to elucidate how the emergence of brain circuits is manifested in variability of infant motor, cognitive and behavioural capacities. In this study, we examined if cortical structural covariance at birth, indexing coordinated development, is related to later infant behaviour. We included 193 healthy term-born infants from the Developing Human Connectome Project (dHCP). An individual cortical connectivity matrix derived from morphological and microstructural features was computed for each subject (morphometric similarity networks, MSNs) and was used as input for the prediction of behavioural scores at 18 months using Connectome-Based Predictive Modeling (CPM). Neonatal MSNs successfully predicted social-emotional performance. Predictive edges were distributed between and within known functional cortical divisions with a specific important role for primary and posterior cortical regions. These results reveal that multi-modal neonatal cortical profiles showing coordinated maturation are related to developmental outcomes and that network organization at birth provides an early infrastructure for future functional skills.

neuroscience↗

bioRxiv2021

Effects of gestational age at birth on perinatal structural brain development in healthy term-born babies

Multiple studies have demonstrated less favourable childhood outcomes in infants born in early term (37-38 weeks gestation) compared to those born at full term (40-41 weeks gestation). While this could be due to higher perinatal morbidity, gestational age at birth may also have a direct effect on the brain and subsequent neurodevelopment in term-born babies. Here we characterise structural brain correlates of gestational age at birth in healthy term-born neonates and their relationship to later neurodevelopmental outcome. We used T2 and diffusion weighted Magnetic Resonance Images acquired in the neonatal period from a cohort (n=454) of healthy babies born at term age (>37 weeks gestation) and scanned between 1 and 41 days after birth. Images were analysed using tensor based morphometry (TBM) and tract based spatial statistics (TBSS). Neurodevelopment was subsequently assessed at age 18 months using the Bayley-III Scales of Infant and Toddler Development, and the effects of gestational age at birth and related neuroimaging findings on outcome were analysed with linear regression. Infants born earlier had areas of higher relative ventricular volume, and lower relative brain volume in the basal ganglia, cerebellum and brainstem. Earlier birth was also associated with lower fractional anisotropy, higher mean, axial and radial diffusivity in major white matter tracts. Gestational age at birth was positively associated with all Bayley-III subscales at age 18 months. Linear regression models predicting outcome from gestational age at birth were significantly improved by adding neuroimaging features associated with gestational age at birth. This work adds to the growing body of evidence of the impact of early term birth and highlights the importance of considering the effect of gestational age at birth in future neuroimaging studies including term-born babies.

neuroscience↗

bioRxiv2021

Harmonised segmentation of neonatal brain MRI

Deep learning based medical image segmentation has shown great potential in becoming a key part of the clinical analysis pipeline. However, many of these models rely on the assumption that the train and test data come from the same distribution. This means that such methods cannot guarantee high quality predictions when the source and target domains are dissimilar due to different acquisition protocols, or biases in patient cohorts. Recently, unsupervised domain adaptation (DA) techniques have shown great potential in alleviating this problem by minimizing the shift between the source and target distributions, without requiring the use of labelled data in the target domain. In this work, we aim to predict tissue segmentation maps on T2-weighted (T2w) magnetic resonance imaging (MRI) data of an unseen preterm-born neonatal population, which has both different acquisition parameters and population bias when compared to our training data. We achieve this by investigating two unsupervised DA techniques with the objective of finding the best solution for our problem. We compare the two methods with a baseline fully-supervised segmentation network and report our results in terms of Dice scores obtained on our ground truth test dataset. Moreover, we analyse tissue volumes and cortical thickness (CT) measures of the harmonised data on a subset of the population matched for gestational age (GA) at birth and postmenstrual age (PMA) at scan. Finally, we demonstrate the applicability of the harmonised cortical gray matter maps with an analysis comparing term and preterm-born neonates and a proof-of-principle investigation of the association between CT and a language outcome measure.

neuroscience↗

bioRxiv2019

Altered cortical gyrification in adults who were born very preterm and its associations with cognition and mental health

BackgroundThe last trimester of pregnancy is a critical period for the establishment of cortical gyrification and altered folding patterns have been reported following very preterm birth (< 33 weeks of gestation) in childhood and adolescence. However, research is scant on the persistence of such alterations in adulthood and their associations with cognitive and psychiatric outcomes. MethodsWe studied 79 very-preterm adults and 81 age-matched full-term controls. T1-weighted images were used to measure local gyrification index (LGI), indicating the degree of folding across multiple vertices of the reconstructed cortical surface. Group and group-sex LGI differences were assessed using per-vertex adjustment for cortical thickness and overall intracranial volume. Within-group correlations were also computed between LGI and functional outcomes, including general intelligence (IQ) and psychopathology. ResultsVery preterm adults had significantly reduced LGI in extensive cortical regions encompassing the frontal, anterior temporal and occipito-parietal lobes. Alterations in lateral fronto-temporal-parietal and medial occipito-parietal regions were present in both males and females, although males reported more extensive alterations. In both very preterm adults and controls, higher LGI was associated with higher IQ and lower psychopathology scores, with the spatial distribution of these associations substantially differing between the two groups. ConclusionsVery preterm adults brains are characterized by significant and widespread local hypogyria and these abnormalities might be implicated in cognitive and psychiatric outcomes. Gyrification reflects an early developmental process and provides a fingerprint for very preterm birth.

neuroscience↗