Comprehensive volumetric phenotyping of the neonatal brain in Down syndrome.

Fukami - Gartner, A.; Baburamani, A.; Dimitrova, R.; Patkee, P. A.; Ojinaga Alfageme, O.; Bonthrone, A. F.; Cromb, D.; Uus, A.; Counsell, S. J.; Hajnal, J. V.; O'Muircheartaigh, J.; Rutherford, M. A.

doi:10.1101/2022.09.30.510205

bioRxiv · 10.1101/2022.09.30.510205

Comprehensive volumetric phenotyping of the neonatal brain in Down syndrome.

Fukami - Gartner, A.·Baburamani, A.·Dimitrova, R.·Patkee, P. A.·Ojinaga Alfageme, O.·Bonthrone, A. F.·Cromb, D.·Uus, A.·Counsell, S. J.·Hajnal, J. V.·O'Muircheartaigh, J.·Rutherford, M. A.

View original source ↗Export metadata ↓

Abstract

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

Source connections

Published article ↗

Explore related subjects

neuroscience Preprint

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

Fukami - Gartner, A., Baburamani, A., Dimitrova, R., Patkee, P. A., Ojinaga Alfageme, O., Bonthrone, A. F., Cromb, D., Uus, A., Counsell, S. J., Hajnal, J. V., O'Muircheartaigh, J., Rutherford, M. A.. 2022-10-03. Comprehensive volumetric phenotyping of the neonatal brain in Down syndrome.. https://doi.org/10.1101/2022.09.30.510205

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Same Movements, Different Skills: How Context Shapes Learning in Humans and Neural Networks

What determines whether experiences are integrated into shared representations or split? Motor skill learning offers a revealing test: when two tasks require an identical sequence of movements, both intuition and theory suggest that practice in one should generalize to the other. Yet we find that changing context can make identical movements different skills. In simple recurrent networks trained on the same sequence across contexts, splitting was greatest when strong contextual inputs coincided with a high initial weight scale; neither alone sufficed. Greater representational separation coincided with separate context-specific learning curves. Humans practicing the same finger sequence while alternating between two performance-irrelevant contexts likewise exhibited context-specific curves, rather than the single continuous trajectory observed when practicing in a single context. State-space modeling favored split learning states in humans and very weakly coupled states in the most context-dependent networks. These findings have broader implications for understanding how learning generalizes across contexts.

neuroscience↗

bioRxiv2026

Postpartum resource scarcity reshapes maternal care, offspring prioritization, and the steroid-sensitive medial preoptic area

Parental care requires balancing offspring needs with environmental constraints, yet how resource scarcity alters the organization of maternal responses remains poorly understood. Here, we examined maternal behavior, offspring prioritization, and steroid receptor-associated extracellular matrix organization in postpartum rats exposed to limited bedding and nesting (LBN) or control conditions with ample nesting materials. LBN increased pup-directed and reduced self-directed behaviors but also increased behavioral entropy, a measure of behavioral fragmentation, indicating less predictable caregiving sequences. LBN dams preferentially retrieved male pups first, whereas control dams preferentially retrieved females first. LBN also increased the proportion of pup-investigation time directed toward males compared with controls. In offspring on postnatal day 10, corticosterone was elevated in female but not male LBN pups, a pattern that paralleled the maternal male bias. To identify associated neurobiological changes, we assessed steroid receptors and extracellular matrix organization in the medial preoptic area (mPOA), a key region for maternal behavior. LBN increased numbers of estrogen receptor (ER)- and androgen receptor (AR)-immunoreactive cells, reduced perineuronal net (PNN) abundance, and decreased receptor-positive cell enwrapment. Because PNNs constrain structural plasticity, these findings suggest that the postpartum environment alters the organization of steroid receptor-associated extracellular matrix, potentially modulating experience-dependent plasticity in neurosteroid-sensitive circuits. In sum, LBN increases the levels of maternal engagement while reshaping its temporal organization and allocation, accompanied by selective remodeling of steroid-sensitive preoptic architecture. Therefore, maternal adaptation to adversity may be better understood as changes in caregiving allocation strategies rather than a simple gain or loss of maternal care.

neuroscience↗

bioRxiv2026

The Computational Grammar of Human Behaviour in a Biological Environment

Human behaviour unfolds as an extended stream of spontaneous actions shaped by environmental demands and the agent's goals. The organisation of these actions, situated between setting abstract goals and concrete movement execution, remains poorly characterised. Here, we introduce DynaClade, an unsupervised temporal action segmentation algorithm for human full-body motion capture data, and apply it to freely moving participants navigating ecologically realistic risky foraging environments in virtual reality. DynaClade identifies discrete actions whose kinematic characteristics and spatial distributions correspond to environmental affordances, supporting the validity of the approach. Among these actions, we discovered a hitherto undescribed movement pattern defined by increased body sway without locomotion. Action sequences were highly non-random and showed clear history dependence beyond first-order Markov structure, most of which was explained by a second-order prediction. This higher-order structure was well captured in a hidden Markov model, in which some of the observed actions were associated with more than one latent state. Each of these latent states corresponded to the same action in a distinct action context. These findings suggest that spontaneous human actions are predominantly selected based on the current action and context, rather than following pre-planned or habitually assembled sequences.

neuroscience↗