Biology subjects

The BIOCARD Study Team,

Publications and source records attributed to The BIOCARD Study Team,.

5 recordsLinked to original sources

bioRxiv2026

Automated Segmentation of Brainstem and Subcortical White Matter: Mapping the Deep Tegmental Core with BundleParc

Diffusion MRI enables noninvasive mapping of human white matter pathways, but automated segmentation methods have largely focused on large association, projection, and commissural bundles. Brainstem and subcortical pathways supporting basal ganglia, cerebellar, limbic/reward, sensory, and homeostatic functions remain underrepresented in large-scale connectomic analyses. To address this gap, we adapted BundleParc, a recently introduced bundle-parcellation architecture, into an automated pipeline for direct segmentation and along-tract parcellation of 97 subcortical and brainstem white matter pathways. The model was trained on a curated reference dataset derived from Human Connectome Project diffusion MRI using anatomy-guided tractography, explicit inclusion and exclusion criteria, automated outlier filtering, and manual quality assurance. Operating directly on native-space fiber orientation distributions, the algorithm successfully recovers these intricate anatomical trajectories and ordered parcellations. We show the model generalizes to diverse external datasets spanning development, aging, and neurodegenerative disease cohorts, maintaining robust performance across variations in spatial resolution and angular sampling. The released container, trained model, population atlas, reference streamlines, and quality assurance outputs provide a resource for studying deep brainstem and subcortical pathways in development, aging, disease, and neuromodulation-relevant anatomy.

neuroscience↗

bioRxiv2026

Analytic Bounds on GAMLSS Model Variability of Normative White Matter Brain Charts

Brain charts, or normative models of quantitative neuroimaging measures, can identify trajectories of brain development and abnormalities in groups and individuals by leveraging large populations. Recent work has extended these brain charts to model microstructural and macrostructural features of white matter. Assessments of variance for these brain charts are necessary to determine whether the models being used for these data are stable. We implement an analytic approach to characterize variability of the parameters in previously released brain charts created using the generalized additive models for location, scale, and shape (GAMLSS) framework. Additionally, we empirically validate the accuracy of each analytic model through a comparison to a bootstrapping approach from 0.2 to 90 years of age. We find that across all models, the analytic coefficient of variation (COV) remains below 5% for ages greater than 0.25 years, with the maximum empirical observed COV reaching 7% at 0.2 years of age. Further, the empirical assessment shows high agreement with the analytic assessment, with COV estimates averaged across the lifespan for all models having a Pearson correlation coefficient of 0.776 and a mean difference of 4 x 10-4. Both methods exhibit volume and surface area as the features with the largest average COV for the majority of tracts. However, the analytic assessment yields axial diffusivity as the feature most frequently having the smallest COV, whereas the corresponding feature for the empirical assessment is average length. These results suggest that the analytic approach overestimates model stability for WM brain charts when the COV is low and that the validation method is suitable for assessing whether GAMLSS models are unstable.

bioengineering↗

bioRxiv2025

Lifespan Trajectories of Asymmetry in White Matter Tracts

Asymmetry in white matter is believed to give rise to the brains capacity for specialized processing and is involved in the lateralization of various cognitive processes, such as language and visuo-spatial reasoning. Although studies of white matter asymmetry have been previously documented, they have often been constrained by limited age ranges, sample sizes, or the scope of the tracts and structural features examined. While normative lifespan charts for brain structures are emerging, comprehensive charts detailing white matter asymmetries across numerous pathways and diverse structural measures have been notably absent. This study addresses this gap by leveraging a large-scale dataset of 35,120 typically developing and aging individuals, ranging from 0 to 100 years of age, from 50 primary neuroimaging studies. We generated comprehensive lifespan trajectories for 30 lateralized association and projection white matter tracts, examining 6 distinct microstructural and macrostructural features of these pathways. Our findings reveal that: (1) asymmetries are widespread across the brains white matter and are present in all 30 pathways; (2) for a given pathway, the degree and direction of asymmetry differ between features of tissue microstructure and pathway macrostructure; (3) asymmetries vary across and within pathway types (association and projection tracts); and (4) these asymmetries are not static, following unique trajectories across the lifespan, with distinct changes during development, and a general trend of becoming more asymmetric with increasing age (particularly in later adulthood) across pathways. This study represents the most extensive characterization of white matter asymmetry across the lifespan to date, charting how lateralization patterns emerge, mature, and change throughout life. It provides a foundational resource for understanding the principles of white matter organization from early to late life, its relation to functional specialization and inter-individual variability, and offers a key reference for interpreting deviations during healthy development and aging as well as those associated with clinical populations.

neuroscience↗

bioRxiv2025

White matter microstructure and macrostructure brain charts across the human lifespan

Normative reference charts are widely used in healthcare, especially for assessing the development of individuals by benchmarking anatomic and physiological features against population trajectories across the lifespan. Recent work has extended this concept to gray matter morphology in the brain, but no such reference framework currently exists for white matter (WM) even though WM constitutes the essential substrate for neuronal communication and large-scale network integration. Here, we present the first comprehensive WM brain charts, which describe how microstructural and macrostructural features of WM evolve across the lifespan, by leveraging over 35,120 diffusion MRI scans from 50 harmonized studies. Using generalized additive models for location, scale, and shape (GAMLSS), we estimate age- and sex-stratified trajectories for 72 individual white matter pathways, quantifying both tract-specific microstructural and morphometric features. We demonstrate that these WM brain charts enable four important applications: (1) defining normative trajectories of WM maturation and decline across distinct pathways, (2) identifying previously uncharacterized developmental milestones and spatial gradients of tract maturation, (3) detecting individualized deviations from normative patterns with clinical relevance across multiple neurological disorders, and (4) facilitating standardized, cross-study centile scoring of new datasets. By establishing a unified, interpretable reference framework for WM structure, these brain charts provide a foundational metric for research and clinical neuroscience. The accompanying open-access trajectories, centile scoring tools, and harmonization methods facilitate precise mapping of WM development, aging, and pathology across diverse populations. We release the brain charts and provide an out-of-sample alignment process as a Docker image: https://zenodo.org/records/17561821.

neuroscience↗

bioRxiv2024

Sex, racial, and APOE-ϵ4 allele differences in longitudinal white matter microstructure in multiple cohorts of aging and Alzheimer's disease

Structured AbstractO_ST_ABSINTRODUCTIONC_ST_ABSThe effects of sex, race, and Apolipoprotein E (APOE) - Alzheimers disease (AD) risk factors - on white matter integrity are not well characterized. METHODSDiffusion MRI data from nine well-established longitudinal cohorts of aging were free-water (FW)-corrected and harmonized. This dataset included 4,702 participants (age=73.06 {+/-} 9.75) with 9,671 imaging sessions over time. FW and FW-corrected fractional anisotropy (FAFWcorr) were used to assess differences in white matter microstructure by sex, race, and APOE-{varepsilon}4 carrier status. RESULTSSex differences in FAFWcorr in association and projection tracts, racial differences in FAFWcorr in projection tracts, and APOE-{varepsilon}4 differences in FW limbic and occipital transcallosal tracts were most pronounced. DISCUSSIONThere are prominent differences in white matter microstructure by sex, race, and APOE- {varepsilon}4 carrier status. This work adds to our understanding of disparities in AD. Additional work to understand the etiology of these differences is warranted. HighlightsO_LISex, race, and APOE-{varepsilon}4 carrier status relate to white matter microstructural integrity C_LIO_LIFemales generally have lower FAFWcorr compared to males C_LIO_LINon-Hispanic Black adults generally have lower FAFWcorr than non-Hispanic White adults C_LIO_LIAPOE-{varepsilon}4 carriers tended to have higher FW than non-carriers C_LI Research in Context Systematic ReviewThe authors used PubMed and Google Scholar to review literature that used conventional and free-water (FW)-corrected microstructural metrics to evaluate sex, race, and APOE-{varepsilon}4 differences in white matter microstructure. While studies have previously explored differences by sex and APOE-{varepsilon}4 status, less is known about racial differences and no large-scale FW-corrected analysis has been performed. InterpretationSex and race were more associated with FAFWcorr while APOE-{varepsilon}4 status was associated with FW metrics. Association, projection, limbic, and occipital transcallosal tracts showed the greatest differences. Future DirectionFuture studies to determine the biological and social pathways that lead to sex, racial, and APOE-{varepsilon}4 differences are warranted. Consent StatementAll participants provided informed consent in their respective cohort studies.

neuroscience↗