Biology subjects

Lepage, C.

Publications and source records attributed to Lepage, C..

11 recordsLinked to original sources

bioRxiv2025

Multiscale characterisation of the human claustrum from histology to MRI

Though linked to an unusually broad array of functions, the human claustrums complex morphology has hindered in vivo study, resulting in a small MRI literature marked by implausibly large discrepancies in reported characteristics. We constructed the first three-dimensional histological "gold standard" claustrum model, and systematically evaluated in vivo 7-Tesla MRI datasets against it and downsampled derivatives. MRI showed resolution-dependent differences rather than contrast limitations, transforming the claustrums intricate sheet into an artefactually thickened ribbon. However, submillimetre MRI reliably recovered the dorsal "core" that contains most claustral volume and density and houses major corticoclaustral connectivity. At 0.5mm resolution, extension into the temporal lobe, including irregular ventral "puddles", was partially recovered, with uncertainty reflecting boundary imprecision rather than anatomical loss. Our results refute the view that the claustrum is inaccessible in the living human brain, define practical measurement limits, and provide a foundation for future functional investigations.

neuroscience↗

bioRxiv2025

Cellular basis for cortical network aging in primates

Large-scale brain networks are vulnerable to change with aging and become dysregulated. How these networks are altered at the cellular level remains unclear owing to challenges of bridging data across scales. Here, we integrate in vivo cortical similarity networks with whole brain spatial transcriptomics to characterize the aging brain in a lifespan cohort of macaques (N=64, ages 1-26 years). Deep-layer excitatory neurons and oligodendrocytes emerged as dominant correlates of cortical similarity, linking infragranular cell type composition to macroscopic network structure. Age-related declines in network strength were most pronounced in transmodal networks, including default mode and limbic, and aligned with regions enriched in inhibitory and glial cell types. Parvalbumin-enriched chandelier cells showed the strongest association with regional vulnerability, suggesting a role in network disconnection. Cell-type enrichment was conserved across species, with both human and macaque transcriptomic data aligning with the cortical functional hierarchy. These findings uncover a cellular basis for cortical network aging and highlight the value of imaging-transcriptomic integration across scales.

neuroscience↗

bioRxiv2024

Seabird and sea duck mortalities were lower during the second breeding season in eastern Canada following the introduction of Highly Pathogenic Avian Influenza A H5Nx viruses

H5N1 clade 2.3.4.4b viruses have caused significant mortality events in various wild bird species across Europe, North America, South America, and Africa. In North America, the largest impacts on wild birds have been in eastern Canada, where over 40,391 wild birds were reported to have died from highly pathogenic avian influenza (HPAI) between April and September 2022. In the year following, we applied previously established methods to quantify total reported mortality in eastern Canada for a full year October 2022, to September 2023. In this study, we (i) document the spatial, temporal and taxonomic patterns of wild bird mortality in the 12 months that followed the mass mortality event in the summer of 2022 and (ii) quantify the observed differences in mortality across the breeding season (April to September) of 2022 and 2023. In eastern Canada, there was high uncertainty about whether 2023 would bring another year of devastating HPAI-linked mortalities. Mortalities in the breeding season were 93% lower in 2023 compared to 2022 but encompassed a more taxonomically diverse array of species. We found that mortalities in the fall and winter (non-breeding season) were dominated by waterfowl, while mortalities during the spring and summer (breeding season) were dominated by seabirds. Due to a low prevalence of HPAI among the subset of tested birds, we refrained from broadly attributing reported mortalities in 2023 to HPAI. However, our analysis did identify three notable mortality events linked to HPAI, involving at least 1,646 Greater Snow Geese, 232 Canada Geese, and 212 Northern Gannets. This study emphasizes the ongoing need for H5NX surveillance and mortality assessments as the patterns of mortality in wild populations continue to change.

ecology↗

bioRxiv2024

Wild bird mass mortalities in eastern Canada associated with the Highly Pathogenic Avian Influenza A(H5N1) virus, 2022

In 2022, a severe outbreak of clade 2.3.4.4b Highly Pathogenic Avian Influenza (HPAI) H5N1 virus resulted in unprecedented mortality among wild birds in eastern Canada. Tens of thousands of birds were reported sick or dead, prompting a comprehensive assessment of mortality spanning the breeding season between April 1 and September 30, 2022. Mortality reports were collated from federal, Indigenous, provincial, and municipal agencies, the Canadian Wildlife Health Cooperative, non-governmental organizations, universities, and citizen science platforms. A scenario analysis was conducted to refine mortality estimates, accounting for potential double counts from multiple sources under a range of spatial and temporal overlap. Correcting for double counting, an estimated 40,966 wild birds were reported sick or dead in eastern Canada during the spring and summer of 2022. Seabirds and sea ducks, long-lived species that are slow to recover from perturbations, accounted for 98.7% of reported mortalities. Mortalities were greatest among Northern Gannets (Morus bassanus; 26,193), Common Murres (Uria aalge; 8,133), and American Common Eiders (Somateria mollissima dresseri; 1,945), however, these figures underestimate total mortality as they exclude unreported deaths on land and at sea. In addition to presenting mortality estimates, we compare mortalities with known population sizes and trends and make an initial assessment of whether population-level impacts are possible for the Northern Gannet, a species that has suffered significant global mortality, and two harvested species, Common Murre and American Common Eider, to support management decisions. We hypothesize that population-level impacts in eastern Canada are possible for Northern Gannets and American Common Eiders but are unlikely for Common Murres. This study underscores the urgent need for further research to understand the broader ecological ramifications of the HPAI outbreak on wild bird populations.

zoology↗

bioRxiv2022

3D reconstruction of ultra-high resolution neurotransmitter receptor atlases in human and non-human primate brains

Quantitative maps of neurotransmitter receptor densities are important tools for characterising the molecular organisation of the brain and key for understanding normal and pathologic brain function and behaviour. We describe a novel method for reconstructing 3-dimensional cortical maps for data sets consisting of multiple different types of 2-dimensional post-mortem histological sections, including autoradiographs acquired with different ligands, cell body and myelin stained sections, and which can be applied to data originating from different species. The accuracy of the reconstruction was quantified by calculating the Dice score between the reconstructed volumes versus their reference anatomic volume. The average Dice score was 0.91. We were therefore able to create atlases with multiple accurately reconstructed receptor maps for human and macaque brains as a proof-of-principle. Future application of our pipeline will allow for the creation of the first ever set of ultra-high resolution 3D atlases composed of 20 different maps of neurotransmitter binding sites in 3 complete human brains and in 4 hemispheres of 3 different macaque brains.

neuroscience↗

bioRxiv2021

BigBrainWarp: Toolbox for integration of BigBrain 3D histology with mutlimodal neuroimaging

AO_SCPLOWBSTRACTC_SCPLOWNeuroimaging stands to benefit from emerging ultrahigh-resolution histological atlases of the human brain; the first of which is "BigBrain". Ongoing research aims to characterise regional differentiation of cytoarchitecture with BigBrain and to optimise registration of BigBrain with standard neuroimaging templates. Together, this work paves the way for multi-scale investigations of brain organisation. However, working with BigBrain can present new challenges for neuroimagers, including dealing with cellular resolution neuroanatomy and complex transformation procedures. To simplify workflows and support adoption of best practices, we developed BigBrainWarp, a toolbox for integration of BigBrain with multimodal neuroimaging. The primary BigBrainWarp function wraps multiple state-of-the-art deformation matrices into one line of code, allowing users to easily map data between BigBrain and standard MRI spaces. Additionally, the toolbox contains ready-to-use cytoarchitectural features to improve accessibility of histological information. The present article discusses recent contributions to BigBrain-MRI integration and demonstrates the utility of BigBrainWarp for further investigations.

neuroscience↗

bioRxiv2021

Robust T1 MRI cortical surface pipeline for neonatal brain and systematic evaluation using multi-site MRI datasets

The human brain grows the most dramatically during the perinatal and early postnatal periods, during which preterm birth or perinatal injury that may alter brain structure and lead to developmental anomalies. Thus, characterizing cortical thickness of developing brains remains an important goal. However, this task is often complicated by inaccurate cortical surface extraction due to small-size brains. Here, we propose a novel complex framework for the reconstruction of neonatal WM and pial surfaces, accounting for large partial volumes due to small-size brains. The proposed approach relies only on T1-weighted images unlike previous T2-weighted image-based approaches while only T1-weighted images are sometimes available under the different clinical/research setting. Deep neural networks are first introduced to the neonatal MRI pipeline to address the mis-segmentation of brain tissues. Furthermore, this pipeline enhances cortical boundary delineation using combined models of the CSF/GM boundary detection with edge gradient information and a new skeletonization of sulcal folding where no CSF voxels are seen due to the limited resolution. We also proposed a systematic evaluation using three independent datasets comprising 736 preterm and 97 term neonates. Qualitative assessment for reconstructed cortical surfaces shows that 86.9% are rated as accurate across the three site datasets. In addition, our landmark-based evaluation shows that the mean displacement of the cortical surfaces from the true boundaries was less than a voxel size (0.532{+/-}0.035mm). Evaluating the proposed pipeline (namely NEOCIVET 2.0) shows the robustness and reproducibility across different sites and different age-groups. The mean cortical thickness measured positively correlated with postmenstrual age (PMA) at scan (p<0.0001); Cingulate cortical areas grew the most rapidly whereas the inferior temporal cortex grew the least rapidly. The range of the cortical thickness measured was biologically congruent (1.3mm at 28 weeks of PMA to 1.8mm at term equivalent). Cortical thickness measured on T1 MRI using NEOCIVET 2.0 was compared with that on T2 using the established dHCP pipeline. It was difficult to conclude that either T1 or T2 imaging is more ideal to construct cortical surfaces. NEOCIVET 2.0 has been open to the public through CBRAIN (https://mcin-cnim.ca/technology/cbrain/), a web-based platform for processing brain imaging data.

bioinformatics↗

bioRxiv2020

CIVET-Macaque: an automated pipeline for MRI-based cortical surface generation and cortical thickness in macaques

The MNI CIVET pipeline for automated extraction of cortical surfaces and evaluation of cortical thickness from in-vivo human MRI has been extended for processing macaque brains. Processing is performed based on the NIMH Macaque Template (NMT), as the reference template, with the anatomical parcellation of the surface following the D99 and CHARM atlases. The modifications needed to adapt CIVET to the macaque brain are detailed. Results have been obtained using CIVET-macaque to process the anatomical scans of the 31 macaques used to generate the NMT and another 95 macaques from the PRIME-DE initiative. It is anticipated that the open usage of CIVET-macaque will promote collaborative efforts in data collection and processing, sharing, and automated analyses from which the non-human primate brain imaging field will advance.

neuroscience↗

bioRxiv2020

A collaborative resource platform for non-human primate neuroimaging

Neuroimaging non-human primates (NHPs) is a growing, yet highly specialized field of neuroscience. Resources that were primarily developed for human neuroimaging often need to be significantly adapted for use with NHPs or other animals, which has led to an abundance of custom, in-house solutions. In recent years, the global NHP neuroimaging community has made significant efforts to transform the field towards more open and collaborative practices. Here we present the PRIMatE Resource Exchange (PRIME-RE), a new collaborative online platform for NHP neuroimaging. PRIME-RE is a dynamic community-driven hub for the exchange of practical knowledge, specialized analytical tools, and open data repositories, specifically related to NHP neuroimaging. PRIME-RE caters to both researchers and developers who are either new to the field, looking to stay abreast of the latest developments, or seeking to collaboratively advance the field.

neuroscience↗

bioRxiv2019

A molecular gradient along the longitudinal axis of the human hippocampus informs large-scale behavioral systems

The functional organization of the hippocampus is distributed as a gradient along its longitudinal axis that explains its differential interaction with diverse brain systems. We show that the location of human tissue samples extracted along the longitudinal axis of the hippocampus can be predicted within 2mm using the expression pattern of less than 100 genes. When variation in this specific gene expression pattern was observed across the whole brain, a distinct anterioventral-posteriodorsal gradient was observed. Frontal, anterior temporal and brainstem regions involved in social and motivational behaviors, selectively vulnerable to frontotemporal dementia and more functionally connected to the anterior hippocampus could be clearly differentiated from posterior parieto-occipital and cerebellar regions involved in spatial cognition, selectively vulnerable to Alzheimers disease, and more functionally connected to the posterior hippocampus. These findings place the human hippocampus at the interface of two major brain systems defined by a single distinct molecular gradient. (148/150)

neuroscience↗

bioRxiv2019

Automated segmentation of cortical layers in BigBrain reveals divergent cortical and laminar thickness gradients in sensory and motor cortices.

Histological atlases of the cerebral cortex, such as those made famous by Brodmann and von Economo, are invaluable for understanding human brain microstructure and its relationship with functional organization in the brain. However, these existing atlases are limited to small numbers of manually annotated samples from a single cerebral hemisphere, measured from 2D histological sections. We present the first whole-brain quantitative 3D laminar atlas of the human cerebral cortex. This atlas was derived from a 3D histological model of the human brain at 20 micron isotropic resolution (BigBrain), using a convolutional neural network to segment, automatically, the cortical layers in both hemispheres. Our approach overcomes many of the historical challenges with measurement of histological thickness in 2D and the resultant laminar atlas provides an unprecedented level of precision and detail. We utilized this BigBrain cortical atlas to test whether previously reported thickness gradients, as measured by MRI in sensory and motor processing cortices, were present in a histological atlas of cortical thickness, and which cortical layers were contributing to these gradients. Cortical thickness increased across sensory processing hierarchies, primarily driven by layers III, V and VI. In contrast, fronto-motor cortices showed the opposite pattern, with decreases in total and pyramidal layer thickness. These findings illustrate how this laminar atlas will provide a link between single-neuron morphology, mesoscale cortical layering, macroscopic cortical thickness and, ultimately, functional neuroanatomy.

neuroscience↗