Biology subjects

Bonthrone, A. F.

Publications and source records attributed to Bonthrone, A. F..

4 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↗

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↗

bioRxiv2022

Comprehensive volumetric phenotyping of the neonatal brain in Down syndrome.

Down syndrome (DS) is the most common genetic cause of intellectual disability with a wide spectrum of neurodevelopmental outcomes. Magnetic resonance imaging (MRI) has been used to investigate differences in whole and/or regional brain volumes in DS from infancy to adulthood. However, to date, there have been relatively few in vivo neonatal brain imaging studies in DS, despite the presence of clearly identifiable characteristics at birth. Improved understanding of early brain development in DS is needed to assess phenotypic severity and identify appropriate time windows for early intervention. In this study, we used in vivo brain MRI to conduct a comprehensive volumetric phenotyping of the neonatal brain in DS. Using a robust cross-sectional reference sample of close to 500 preterm- to term-born control neonates, we have performed normative modelling and quantified volumetric deviation from the normative mean in 25 individual infants with DS [postmenstrual age at scan, median (range) = 40.57 (32.43 - 45.57) weeks], corrected for sex, age at scan and age from birth. We found that absolute whole brain volume was significantly reduced in neonates with DS (pFDR <0.0001), as were most underlying absolute tissue volumes, except for the lentiform nuclei and the extracerebral cerebrospinal fluid (eCSF), which were not significantly different, and the lateral ventricles, which were significantly enlarged (pFDR <0.0001). Relative volumes, adjusting for underlying differences in whole brain volume, revealed a dynamic shift in brain proportions in neonates with DS. In particular, the cerebellum, as well as the cingulate, frontal, insular and occipital white matter (WM) segments were significantly reduced in proportion (pFDR <0.0001). Conversely, deep grey matter (GM) structures, such as the thalami and lentiform nuclei, as well as CSF-filled compartments, such as the eCSF and the lateral ventricles were significantly enlarged in proportion (pFDR <0.0001). We also observed proportionally reduced frontal and occipital lobar volumes, in contrast with proportionally enlarged temporal and parietal lobar volumes. Lastly, we noted age-related volumetric differences between neonates with and without a congenital heart defect (CHD), indicating that there may be a baseline brain phenotype in neonates with DS, which is further altered in the presence of CHD. In summary, we provide a comprehensive volumetric phenotyping of the neonatal brain in DS and observe many features that appear to follow a developmental continuum, as noted in older age cohorts. There are currently no paediatric longitudinal neuroimaging investigations in DS, starting from the earliest time points, which greatly impedes our understanding of the developmental continuum of neuroanatomical parameters in DS. Whilst life expectancy of individuals with DS has greatly improved over the last few decades, early interventions may be essential to help improve outcomes and quality of life. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=93 SRC="FIGDIR/small/510205v1_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@15cc92aorg.highwire.dtl.DTLVardef@9af99dorg.highwire.dtl.DTLVardef@79b7dborg.highwire.dtl.DTLVardef@115adfc_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗