Biology subjects

Im, K.

Publications and source records attributed to Im, K..

6 recordsLinked to original sources

bioRxiv2026

A Large-Scale Deep Normative Modeling of Primary Sulcal Patterns Reveals Deviations in a Spectrum of Disorders

Primary sulcal patterns, the spatial arrangement of the earliest cortical folds, emerge prenatally and remain essentially stable after birth. Alterations are associated with cognitive outcomes and hold promise as clinical biomarkers. However, detecting abnormalities is challenging due to the high topological variability and complexity of normal individual sulcal patterns. Here, we introduce an unsupervised generative model that quantifies individual sulcal pattern deviations against a normative baseline learned from 10,349 typically developing subjects spanning early childhood through adulthood. We combine a generative reconstruction error with a discriminator trained on diffusion-generated pseudo-atypical graphs to leverage their complementary strengths in sensitivity and robustness. The discriminator captures subtle anomalies and is robust to demographic and data quality variations, whereas the generative model enables severity stratification and demonstrates cross-site generalizability. Across two clinical cohorts spanning subtle to overt sulcal abnormalities (congenital heart disease and polymicrogyria), our model captured global and localized condition-related deviations and linked them to neurodevelopmental outcomes. By enabling population-scale, individualized quantification of sulcal deviations, this framework provides a foundation for future clinical risk stratification.

neuroscience↗

bioRxiv2026

Fetal MRI Reveals Altered Subplate Development in Congenital Heart Disease

Background: The subplate is a transient fetal brain compartment that provides an early foundation for downstream cerebral development. Congenital heart disease (CHD) alters fetal circulation and cerebral substrate delivery, but its impact on subplate development and whether resulting alterations relate to later neurodevelopmental outcomes remain unclear. Methods: In this retrospective observational cohort study, We used fetal MRI to quantify whole-brain, lobar, and regional (17 bilateral cortical regions) subplate volume and thickness to evaluate group differences between 76 fetuses with CHD and 62 typically developing (TD) fetuses scanned between 21-32 weeks of gestation, and estimated individualized deviations from TD developmental trajectories. Associations with fetal hemodynamic indices (substrate delivery score, cerebroplacental ratio [CPR]) and two-year neurodevelopmental outcomes (Bayley Scales of Infant and Toddler Development, N=46 CHD, N=37 TD) were explored. Results: Whole-brain subplate volume was lower in CHD, corresponding to a 5.7% reduction relative to age- and sex-expected values (p=0.003), but this difference was substantially attenuated after accounting for global brain volume (p=0.090). In contrast, regional analyses identified persistent spatially structured deviations beyond global scaling, most consistently involving posterior parietal, occipital and temporal regions, with a left-hemisphere bias in subplate thickness. Normative modelling demonstrated bidirectional regional deviations and increased inter-individual variability in CHD, with extreme subplate volume deviations enriched across 73% of cortical regions (p=0.009). Higher CPR was associated with lower SP thickness deviations, with the association strengthening after accounting for cerebral substrate delivery (p=0.010), although these analyses were exploratory. In CHD fetuses with postnatal follow-up, prenatal subplate deviations showed modest associations with neurodevelopmental outcomes, with right precuneus subplate thickness associated with receptive ({beta}=-11.87, q=0.017) and expressive ({beta}=-14.50, q=0.039) communication on the Bayley, after correction for multiple comparisons. Conclusions: Fetal subplate alterations in CHD are dominated by global reductions in brain growth but also include spatially heterogeneous and individually variable regional deviations beyond global scaling. Exploratory associations with fetal hemodynamics and postnatal neurodevelopment provide hypotheses for future studies investigating the developmental significance of these prenatal alterations.

neuroscience↗

bioRxiv2026

Fetal MRI reveals altered prenatal cortical surface area in fetuses later diagnosed with autism spectrum disorder

Autism spectrum disorder (ASD) is increasingly conceptualized as a condition rooted in altered prenatal neurodevelopment, yet in vivo evidence from fetal brain imaging remains limited. Using retrospective fetal MRI and surface-based morphometry, we investigated cortical development in 15 fetuses later diagnosed with ASD (77%; mean gestational age [GA] = 26.7 weeks) without major structural brain abnormalities and compared them with 60 typically developing controls (57% male; mean GA = 28.4 weeks). Fetuses later diagnosed with ASD showed significantly reduced whole-brain inner cortical plate surface area compared with controls ({beta} = -0.08 {+/-} 0.02 SE, p = 0.002, partial {superscript 2} = 0.13), corresponding to an estimated [~]7.7% reduction (predicted at GA = 28.1 weeks). Lobar mixed-effects analyses demonstrated broadly distributed reductions across all cortical lobes (FDR-corrected p = <0.001-0.024; Cohens d = -0.06 to -0.10), with modest regional heterogeneity indicating relatively greater frontal and insular involvement (groupxlobe: F = 19.31, p = 0.002, {superscript 2} = 0.08). Surface area findings remained directionally stable across sensitivity analyses, including restriction to neurodevelopmentally confirmed controls and models accounting for image quality variability, although effect sizes were attenuated after quality adjustment. Normative modeling further demonstrated subtle negative deviations from typical prenatal cortical surface area trajectories in ASD (mean Z = -0.27, p = 0.018). These findings suggest that aspects of cortical morphogenesis may diverge prenatally in individuals later diagnosed with ASD and suggest the feasibility of fetal MRI-based surface morphometry for studying early neurodevelopmental variation associated with ASD risk.

neuroscience↗

bioRxiv2025

Typical development of the human fetal subplate: regional heterogeneity, growth, and asymmetry assessed by in vivo T2-weighted MRI

The subplate (SP) is a transient fetal brain compartment supporting neuronal migration, axonal ingrowth, and early cortical activity, yet the dynamics of its regional development remain poorly understood in vivo. Using T2-weighted fetal MRI of 68 typically developing fetuses (22-32 weeks gestational age, GA), we developed a semi-automated pipeline to quantify regional SP morphology (thickness, surface area, and volume). SP characteristics scaled strongly with GA and residual brain volume and showed marked regional differences. After correcting for geometric confounds, regional variation of SP thickness persisted, with highest values in parietal and perisylvian regions, suggesting that SP thickness may serve as a sensitive marker of intrinsic developmental differences. Between late 2nd and early 3rd trimester, mean SP thickness increased by 39.2% with large variation across regions ({+/-}11.0 SD), whereas surface area growth was more uniform (64.3% {+/-}0.7 SD). Continuous growth trajectories clustered into distinct spatiotemporal profiles: early-developing regions (e.g., pericentral and medial occipital cortices) contrasted with later-developing regions (prefrontal, temporal, and parietal cortices). These patterns partially recapitulate primary-to-association, medial-to-lateral, and posterior-to-anterior maturational hierarchies, pointing to organized developmental program. SP development also showed region-specific hemispheric asymmetries, including leftward thickness and volume asymmetry in superior temporal and precentral gyri. Some asymmetries amplified, others attenuated or reversed with age, suggesting both transient states and potential precursors of postnatal lateralization. Together, these findings provide a framework for regional SP quantification and position SP morphology, particularly thickness, as a promising early biomarker that might link fetal SP changes to subsequent cortical development and neurodevelopmental outcomes. Significance StatementThe subplate (SP) is a transient fetal brain compartment that provides an early foundation for downstream cerebral development. Using fetal MRI, we show that SP morphology is regionally heterogeneous and that its growth follows distinct regional trajectories. Principal spatiotemporal patterns differentiate early-from later-developing regions and partially recapitulate sensory-to-association hierarchies of cortical maturation. SP also exhibits dynamic hemispheric asymmetries as early as the second trimester, with some amplifying as potential precursors of postnatal lateralization, and others reversing with age, emphasizing the importance of evaluating developmental trajectories rather than single time points. This framework positions SP morphology as an accessible early marker of fetal brain organization with potential relevance for later neurodevelopment.

neuroscience↗

bioRxiv2023

Dynamic changes in subplate and cortical plate microstructure precede the onset of cortical folding in vivo

Cortical gyrification takes place predominantly during the second to third trimester, alongside other fundamental developmental processes, such as the development of white matter connections, lamination of the cortex and formation of neural circuits. The mechanistic biology that drives the formation cortical folding patterns remains an open question in neuroscience. In our previous work, we modelled the in utero diffusion signal to quantify the maturation of microstructure in transient fetal compartments, identifying patterns of change in diffusion metrics that reflect critical neurobiological transitions occurring in the second to third trimester. In this work, we apply the same modelling approach to explore whether microstructural maturation of these compartments is correlated with the process of gyrification. We quantify the relationship between sulcal depth and tissue anisotropy within the cortical plate (CP) and underlying subplate (SP), key transient fetal compartments often implicated in mechanistic hypotheses about the onset of gyrification. Using in utero high angular resolution multi-shell diffusion-weighted imaging (HARDI) from the Developing Human Connectome Project (dHCP), our analysis reveals that the anisotropic, tissue component of the diffusion signal in the SP and CP decreases immediately prior to the formation of sulcal pits in the fetal brain. By back-projecting a map of folded brain regions onto the unfolded brain, we find evidence for cytoarchitectural differences between gyral and sulcal areas in the late second trimester, suggesting that regional variation in the microstructure of transient fetal compartments precedes, and thus may have a mechanistic function, in the onset of cortical folding in the developing human brain.

neuroscience↗

bioRxiv2022

CD244 regulates both innate and adaptive immune axes in melanoma by inhibiting autophagy-mediated M1 macrophage maturation

Accumulating data have highlighted the role of monocytes/macrophages in immune escape by generating immunologically "cold" tumors that do not respond to immunotherapy. CD244 (SLAMF4, 2B4), a member of the signaling lymphocyte activation molecule family, is expressed on myeloid cells, but its precise role has not been elucidated. Using monocyte lineage-specific CD244-deficient (LysM-cre+/-CD244fl/fl;cKO) mice challenged with B16F10 melanoma, we report for the first time that CD244 negatively regulates tumor immunity by inhibiting the differentiation and functional maturation of CD11b+Ly6ChiF4/80lo monocytes into CD11b+Ly6CloF4/80hi macrophages within the tumor microenvironment. CD244-deficient macrophages more effectively activated antigen-specific T cell responses compared to WT macrophages, thus delaying tumor growth in the B16F10 melanoma model. Moreover, combinatorial intervention of anti-PD-L1 antibodies with CD244-KO BMDM markedly improved tumor rejection compared to the anti-PD-L1 antibody alone or in combination with WT BMDM. Consistent with the murine data, transcriptome analysis of human melanoma tissue single-cell RNA-sequencing dataset (SCP398 from single-cell portal), revealed 221 differentially expressed genes of CD244- monocytes/macrophages were associated with phagocytosis, antigen presentation, and autophagy. Additionally, cell type deconvolution analysis within melanoma patients bulk RNA-seq datasets from TCGA database, revealed presence of CD244- monocytes/macrophages significantly increased patient survival in primary and metastatic tumors. Hence, we proposed that CD244 serve as a critical immune checkpoint receptor on macrophages, and CD244-deficient macrophages may represent a novel therapeutic modality to convert immunologically "cold" tumors to "hot" tumors, which can function synergistically with checkpoint blockade therapies.

immunology↗