Biology subjects

Luo, A. C.

Publications and source records attributed to Luo, A. C..

11 recordsLinked to original sources

bioRxiv2026

Generalizable sex differences in functional brain organization follow the cortical hierarchy in youth

It remains unknown if sex differences in human functional connectivity follow a generalizable overarching principle. Here, we tested whether sex differences in functional connectivity during childhood and adolescence are organized along the sensorimotor-association (S-A) axis, a cortical hierarchy spanning unimodal sensorimotor to transmodal association cortex. We analyzed four large-scale, independent datasets of youth ages 5-23 years (total N = 3,355). Across datasets, males showed greater connectivity between functional networks, whereas females showed greater connectivity within networks, most prominently within the default mode network. More broadly, the sensorimotor and association ends of the S-A axis were more segregated in females and more integrated in males. This difference extended to macroscale cortical organization: the cortical hierarchy was expanded in females relative to males along the principal gradient of functional connectivity. Together, these findings identify the S-A axis as a generalizable organizing principle of sex differences in functional brain organization during youth.

neuroscience↗

bioRxiv2026

Insula functional connectivity development follows a canonical antero-posterior axis of organization

The insula is a heterogeneous region associated with a range of functional domains including sensory, cognitive, and emotional processing. Cytoarchitectural and functional studies have described an antero-posterior axis of insula organization. However, the insula's functional development remains sparsely described. We delineated the development of insula resting-state functional connectivity across 562 individuals (6-22 years) using generalized additive models and population value decomposition. We show insulo-cortical functional connectivity development differs across the insula: anterior subregions have predominantly decreasing connectivity across the age range examined, whereas posterior subregions have variable connectivity that aligns with the sensorimotor-association axis. Vertex-level analysis revealed that age-related trajectories followed an antero-posterior axis that aligned with estimates of insula microstructure. Our results emphasize that the development of insula connectivity is spatially heterogeneous and aligns with known cytoarchitecture. The normative insula development described here provides a foundation for investigating how emerging psychopathology may be linked to variation in insula development.

neuroscience↗

bioRxiv2026

White matter reflects the childhood exposome

The childhood environment is critical for brain development. However, most neuroimaging studies examine individual environmental measures (e.g., socioeconomic status) or a limited set of exposures, obscuring how the combination of complex, real-world exposures jointly influence brain development. Here we investigated how white matter shape and tissue properties are linked to the childhood exposome, a multidimensional measure capturing over 300 environmental exposures. Using multi-shell diffusion MRI from 8,183 children (ages 9-10) in the ABCD study, we quantified microstructural and macrostructural properties across 62 person-specific white matter tracts. The exposome showed widespread and highly replicable associations with both white matter microstructure and macrostructure: more advantaged environments were associated with larger tract macrostructure and lower orientation dispersion. Principal component analysis revealed that the dominant axis of exposome-white matter covariation aligns with the cortical sensorimotor-association hierarchy, such that tracts spanning this hierarchy exhibit the strongest associations with the exposome. Multivariate models demonstrated that patterns of white matter features explained 25% of the variance in the exposome in unseen individuals. Notably, white matter-based prediction of cognition was markedly reduced after accounting for the exposome ([~]82% reduction in explained variance), indicating that brain-cognition associations overlap substantially with variance captured by the exposome. These findings generalized to independent data from the Healthy Brain Network (n=869), which differs substantially from ABCD in MRI acquisition, participant selection, and childhood environments. Together, these results suggest that white matter architecture strongly reflects the childhood environment.

neuroscience↗

bioRxiv2026

Highly replicable multisite patterns of adolescent white matter maturation

The Adolescent Brain Cognitive Development (ABCD) Study is the largest U.S.-based neuroimaging initiative of adolescent brain maturation. Diffusion MRI (dMRI) provides unique insights into white matter organization, yet applying advanced processing pipelines and managing technical variability across scanning environments remains challenging at scale. To address these issues, we present ABCD-BIDS Community Collection (ABCC) release 3.1.0, including a curated resource of more than 24,000 fully processed ABCD dMRI datasets. ABCC provides fully processed images, nuanced image quality metrics, advanced microstructural measures, and person-specific bundle tractography. Evaluating these rich data revealed that measures of diffusion restriction and non-Gaussianity--in particular the intracellular volume fraction from NODDI and return-to-origin probability from MAP-MRI--were highly sensitive to neurodevelopment and robust to variation in image quality. Additionally, harmonization of microstructural features markedly improved the cross-vendor generalizability of developmental effects. Together, ABCC accelerates reproducible, rigorous research on adolescent white matter development.

neuroscience↗

bioRxiv2026

Mapping developmental patterns of intrinsic timescale

Intrinsic timescale is a commonly used measure of spontaneous neural dynamics that quantifies the temporal window of processing of neuronal populations. Intrinsic timescale displays a hierarchical cortical organization across multiple species and imaging modalities, with shorter timescales in sensorimotor cortex compared to association cortex. However, less is known about how intrinsic timescale evolves during human brain development and whether its cortical maturation patterns generalize to independent developmental samples. Here we estimate the intrinsic timescale in two independent cross-sectional datasets of youth (HCPD: n=565; HBN: n=729; age range 8-22 years) and investigate its neurodevelopmental patterns. We find that developmental patterns in the intrinsic timescale follow a hierarchical pattern that recapitulates an axis spanning sensorimotor to association cortices (S-A axis). Our analysis of an independent healthy young adult dataset (HCPYA: n=973, age range 22-37 years) underscores the specificity of these developmental findings, suggesting that the intrinsic timescale develops along the S-A axis in youth and stabilizes in adulthood. Together, these results reveal convergence between major axes of cortical organization and development, highlighting intrinsic timescale as a principled marker of hierarchical brain maturation in youth.

neuroscience↗

bioRxiv2025

Conditional-longitudinal brain growth charts detect MRI changes with birth weight and psychopathology

ImportanceBrain maturation varies between individuals, particularly during dynamic developmental periods like adolescence. Directly assessing differences in longitudinal trajectories can reveal deviations from normative patterns. ObjectiveWe present novel conditional-longitudinal normative models that characterize variability in brain maturation. We utilize these models to examine whether differences in longitudinal trajectories are associated with birth weight (BW), gestational age (GA), and longitudinal psychopathology derived from behavioral assessments. DesignCross-sectional and conditional-longitudinal normative models were developed for brain volumes derived from the first two neuroimaging timepoints from the Adolescent Brain Cognitive Development (ABCD) Study. Conditional-longitudinal models index an individuals expected brain volume at follow-up conditioned on their baseline measurement. Models were fit with split-half cross-validation on demographically matched samples. SettingThe ABCD Study is a multi-site, population-based study ParticipantsParticipants were excluded based on imaging quality flags and missing data, leaving 10,830 at baseline and 7,262 at follow-up. ExposuresBW and GA were derived from parent-report questionnaires. General psychopathology scores were calculated using a bifactor model. Main Outcomes and MeasuresWe calculated cross-sectional and conditional-longitudinal centiles, respectively quantifying individual deviations in size and change between timepoints. Sensitivity analyses included covariates for parental income and education as well as current weight and height. ResultsThe sample was 10,830 at baseline (48.2% F,age 9-10y) and 7,262 at follow-up (46.6% F,age 11-13y). Conditional-longitudinal centiles were sensitive to individual differences in brain change between timepoints. Lower BW was associated with lower conditional-longitudinal centiles, suggesting larger decreases in brain volumes over time (27 regions pfdr<0.05, {beta}max=0.08). Lower conditional-longitudinal centiles were associated with greater increases in psychopathology scores, suggesting with increased psychopathology brain volumes show greater decrease (37 regions pfdr<0.05, {beta}max=0.06). Notably, changes in psychopathology were not related to brain size at either timepoint, indexed by cross-sectional centiles. Conclusions and RelevanceModels that capture individual-level deviations from expected growth trajectories, rather than static positions on a growth curve, are particularly informative for assessing developmental change. Novel conditional-longitudinal models address this gap in lifespan brain imaging. Using this framework, we demonstrate robust associations between individual trajectory deviations, perinatal adversity, and longitudinally assessed mental health symptoms. Condition-longitudinal models hold promise for applications across psychiatric neuroscience, from development to aging. Key Points QuestionHow do differences in brain maturation trajectories, quantified by novel conditional-longitudinal models, relate to perinatal factors and mental health in adolescence? FindingsIn this longitudinal analysis of neuroimaging data from the Adolescent Brain Cognitive Development (ABCD) Study, conditional-longitudinal normative models revealed that trajectories of brain maturation in adolescence are associated with birth weight, and with longitudinal changes in mental health. MeaningConditional longitudinal models detect inter-individual variability in brain maturation, which is related to both perinatal factors and concurrent changes in psychopathology.

neuroscience↗

bioRxiv2025

Anatomical White Matter Tracts Span the Cortical Hierarchy to Support Cognitive Diversity

Long-range white matter (WM) tracts support cognition by enabling communication between distant cortical regions, which are organized along a hierarchy defined by the sensorimotor-to-association (S-A) axis. However, it remains unknown how WM tracts are positioned within the cortical hierarchy to support cognition. Here, we show that WM tracts are differentially positioned in the cortical hierarchy to support specific cognitive functions, and that tracts spanning the hierarchy connect regions with greater cognitive diversity. Moreover, tracts situated within the same hierarchical level connect biologically similar regions, while those crossing the hierarchy bridge distinct biological milieux to support diverse cognitive functions. The placement of tracts in the cortical hierarchy also reflects developmental variation in tract microstructure and individual differences in cognition. Together, these findings provide a framework that moves beyond conventional categories of association or projection tracts and links WM tract anatomy to cortical organization, cognitive function, cortical neurobiology, and neurodevelopment. We anticipate that this cortex-anchored framework for describing WM tracts may aid the interpretation of individual differences in WM structure related to development and behavior.

neuroscience↗

bioRxiv2025

Benchmarking Orientation Distribution Function Estimation Methods for Tractometry in Single-Shell Diffusion Magnetic Resonance Imaging - An Evaluation of Test-Retest Reliability and Predictive Capability

Deriving white matter (WM) bundles in-vivo has thus far mainly been applied in research settings, leveraging high angular resolution, multi-shell diffusion MRI (dMRI) acquisitions that enable advanced reconstruction methods. However, these advanced acquisitions are both time-consuming and costly to acquire. The ability to reconstruct WM bundles in the massive amounts of existing single-shelled, lower angular resolution data from legacy research studies and healthcare systems would offer much broader clinical applications and population-level generalizability. While legacy scans may offer a valuable, large-scale complement to contemporary research datasets, the reliability of white matter bundles derived from these scans remains unclear. Here, we leverage a large research dataset where each 64-direction dMRI scan was acquired as two independent 32-direction runs per subject. To investigate how recently developed bundle segmentation methods generalize to this data, we evaluated the test-retest reliability of the two 32-direction scans, of WM bundle extraction across three orientation distribution function (ODF) reconstruction methods: generalized q-sampling imaging (GQI), constrained spherical deconvolution (CSD), and single-shell three-tissue CSD (SS3T). We found that the majority of WM bundles could be reliably extracted from dMRI scans that were acquired using the 32-direction, single-shell acquisition scheme. The mean dice coefficient of reconstructed WM bundles was consistently higher within-subject than between-subject for all WM bundles and ODF reconstruction methods, illustrating preservation of person-specific anatomy. Further, when using features of the bundles to predict complex reasoning assessed using a computerized cognitive battery, we observed stable prediction accuracies (r: 0.15-0.36) across the test-retest data. Among the three ODF reconstruction methods, SS3T had a good balance between sensitivity and specificity in external validation, a high intra-class correlation of extracted features, more plausible bundles, and strong predictive performance. More broadly, these results demonstrate that bundle segmentation can achieve robust performance even on lower angular resolution, single-shell dMRI, with particular advantages for ODF methods optimized for single-shell data. This highlights the considerable potential for dMRI collected in healthcare settings and legacy research datasets to accelerate and expand the scope of WM research.

neuroscience↗

bioRxiv2025

An open, fully-processed data resource for studying mood and sleep variability in the developing brain

Brain development during adolescence and early adulthood coincides with shifts in emotion regulation and sleep. Despite this, few existing datasets simultaneously characterize affective dynamics, sleep variation, and multimodal measures of brain development. Here, we describe the study protocol and initial release (n = 10) of an open data resource of neuroimaging paired with densely sampled behavioral measures in adolescents and young adults. All participants complete multi-echo functional MRI, compressed-sensing diffusion MRI, and advanced arterial spin-labeled MRI. Behavioral measures include ecological momentary assessment, actigraphy, extensive cognitive assessments, and detailed clinical phenotyping focused on emotion regulation. Raw and processed data are openly available without a data use agreement and will be regularly updated as accrual continues. Together, this resource will accelerate research on the links between mood, sleep, and brain development.

neuroscience↗

bioRxiv2025

Two Axes of White Matter Development

Despite decades of neuroimaging research, how white matter develops along the length of major tracts in humans remains unknown. Here, we identify fundamental patterns of white matter maturation by examining developmental variation along major, long-range cortico-cortical tracts in youth ages 5-23 years using diffusion MRI from three large-scale, cross-sectional datasets (total N = 2,716). Across datasets, we delineate two replicable axes of human white matter development. First, we find a deep-to-superficial axis, in which superficial tract regions near the cortical surface exhibit greater age-related change than deep tract regions. Second, we demonstrate that the development of superficial tract regions aligns with the cortical hierarchy defined by the sensorimotor-association axis, with tract ends adjacent to sensorimotor cortices maturing earlier than those adjacent to association cortices. These results reveal developmental variation along tracts that conventional tract-average analyses have previously obscured, challenging the implicit assumption that white matter tracts mature uniformly along their length. Such developmental variation along tracts may have functional implications, including mitigating ephaptic coupling in densely packed deep tract regions and tuning neural synchrony through hierarchical development in superficial tract regions - ultimately refining neural transmission in youth.

neuroscience↗

bioRxiv2022

Enhanced intramyocardial vascular cell delivery promotes post-myocardial infarction healing by polarizing pro-regenerative neutrophils

The success of vascular progenitor cell transplantation to treat myocardial infarction (MI) is primarily limited by the low engraftment of delivered cells due to a washout effect during myocardium contraction. A clinically applicable biomaterial to improve cell retention is arguably needed to enable optimization of intramyocardial cell delivery. Here, we developed a novel therapeutic cell delivery method for MI treatment based on a photocrosslinkable gelatin methacryloyl (GelMA) hydrogel. A combination of human vascular progenitor cells (endothelial progenitors and mesenchymal stem cells) with the capacity to form functional vasculatures after transplantation, were injected with a rapid in-situ photopolymerization approach into the infarcted zone of mouse hearts. Our approach significantly improved acute cell retention and achieved a long-term beneficial post-MI cardiac healing, including stabilizing cardiac functions, preserving viable myocardium, and preventing cardiac fibrosis. Furthermore, the engrafted vascular cells polarized recruited bone marrow-derived neutrophils toward a non-inflammatory phenotype via TGF{beta} signaling, establishing a pro-regenerative microenvironment. Depletion of neutrophils canceled the therapeutic benefits produced by cell delivery in the ischemic hearts, indicating that the non-inflammatory, pro-regenerative neutrophils were indispensable mediators of cardiac remodeling. In summary, our novel GelMA hydrogel-based intramyocardial vascular cell delivery approach has the potential to improve the treatment of acute MI.

bioengineering↗