Biology subjects

Mangin, J.-F.

Publications and source records attributed to Mangin, J.-F..

18 recordsLinked to original sources

bioRxiv2026

Clinically Relevant Biomarkers of Alzheimers Disease Are Associated with Age and Cortical Atrophy in Chimpanzees (Pan troglodytes)

Chimpanzees share a number of age-related brain changes with humans, such as reductions in neurons and increases in neuropathology. To date, there are no published studies of peripheral biomarkers related to Alzheimers pathology and their associations with age and cortical atrophy in chimpanzees. Here we examined cross-sectional differences and longitudinal changes in biomarkers of pathological protein aggregation, neuroinflammation, and microglial function measured in serum. We examined the relationships between biomarkers and clinically relevant biomarker ratios with both age and cortical atrophy. We found linear and quadratic relationships between age and several biomarkers and ratios. Most biomarkers increased with age. While controlling for sex, we found significant negative associations between age and sulci surface area, mean depth, and gray matter thickness and a positive association with fold opening. A{beta}42 and A{beta}40 showed higher biomarker values associated with lower surface area, mean depth, and gray matter thickness and higher fold opening values. The clinically relevant biomarker ratios were also associated with cortical atrophy - A{beta}42/A{beta}40 was negatively associated with gray matter thickness, and pTau217/A{beta}42 (both total and brain-derived) was positively associated with surface area and gray matter thickness and negatively associated with fold opening. Consistent with our hypotheses and previous findings in humans, many peripheral biomarkers associated with neurodegeneration and Alzheimers disease increase as chimpanzees age. We believe this is the first evidence demonstrating an association between these clinically relevant biomarkers of Alzheimers disease and phenotypes of brain aging in nonhuman primates, underscoring their importance as models of aging and neurodegenerative disease.

neuroscience↗

bioRxiv2026

Self-supervised representations reveal the genetic architecture of human cortical folding

Cortical folding emerges during fetal development, is under genetic control, and remains stable throughout life, offering a lasting window into early neurodevelopment. Conventional morphometric descriptors, however, only partially capture the shape variability of cortical folds. Here, we compare 56 regional self-supervised deep learning representations of cortical folds with classical sulcal morphometry via multivariate genome-wide association studies (GWAS) in 35,940 UK Biobank participants. The learned representations identified 567 independent genome-wide significant loci, versus 162 for classical morphometry, 87% of which were also detected by our approach. More than half of these associations replicated in the independent Adolescent Brain Cognitive Development (ABCD) cohort. Gene, gene-set, BrainSpan and single-cell expression enrichment converge on a shared prenatal window of neurogenesis and morphogenesis; spatial gene-association maps recapitulate known regional expression gradients, including for NR2F1. Together, these results establish self-supervised representations of cortical folding as a powerful phenotypic framework for the genetic study of neurodevelopment.

genomics↗

bioRxiv2026

FAST BOLD FMRI REVEALS THE SPATIOTEMPORAL COMPLEXITY OF NEUROVASCULAR COUPLING ALTERATIONS IN CEREBRAL SMALL VESSEL DISEASE

Recent advances in neurophysiology highlighted the potential of high temporal resolution in Blood-Oxygen Level Dependent (BOLD) functional MRI (fMRI), although it is not yet standard practice. We demonstrated that fast BOLD fMRI can detect single-subject, single-stimulus visually evoked responses to brief stimuli at 3T. We used fast fMRI in patients with Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL), a genetic form of cerebral small vessel disease (cSVD). Using 2- and 10-second visual stimuli, we probed different neurovascular coupling regimes and showed that different regions of interest detect different facets of vascular dynamics. CADASIL patients showed significant changes in the amplitude and timing of the BOLD response, indicating early-age neurovascular impairment unrelated to anatomical lesions, and providing strong discriminative and generalization performance. These findings resolve prior inconsistencies in fMRI studies of CADASIL, supporting the use of fast fMRI to develop non-invasive biomarkers for cSVD and other neurodegenerative disorders.

neuroscience↗

bioRxiv2026

Cortical folding patterns are encoded in the geometry of the unfolded neocortex.

Cortical folding patterns are conserved across individuals of gyrencephalic species and are closely related to cytoarchitectural organisation, connectivity, and function. Early morphogen gradients have been proposed as the molecular source of positional information encoding these patterns - a gyral molecular protomap - but the contribution of neocortical geometry to this encoding has not been examined. Here we show that the geometry of the unfolded ferret brain guides the adult folding pattern before any folding has occurred. Using high-resolution MRI surface reconstructions from postnatal day (P) 0 to adults, we demonstrate that newborn neocortical curvature predicts mature curvature maps, sulcal-gyral fate, and fold orientation. Pre-folding curvature correlates with expression of key patterning genes, and a mediation analysis indicates that geometry at P0 is the principal predictor of sulcal-gyral fate at P6. Mechanical simulations show that regions of high curvature act as autonomous anchors that organise the folding pattern. These results suggest that neocortical geometry constitutes a form of positional information that complements molecular patterns in regulating cortical organisation, and that a complete account of cortical development requires the integration of geometric and mechanical processes alongside molecular signalling.

neuroscience↗

bioRxiv2025

Siibra: A software tool suite for realizing a Multilevel Human Brain Atlas from complex data resources

Computational technology opens new possibilities towards understanding the complexity of the human brain, but it requires integrating measurements from different modalities and scales in anatomical context and exposing them in interoperable, actionable form. Especially with growing big data resources, accessing information from different scales and modalities coherently for visual exploration, reproducible analysis and application development remains challenging. We present siibra, a tool suite that connects diverse data from cloud resources to reference atlases and coordinate spaces. It supports different use cases by making contents accessible through a web viewer, Python library and HTTP API. Using siibra we implemented a Multilevel Human Brain Atlas linking macro-anatomical concepts and their inter-subject variability with measurements of the microstructural composition and intrinsic variance of brain regions, building on cytoarchitecture as a reference and supporting MRI-based and microscopic templates. The atlas is integrated with the EBRAINS research infrastructure. All software and content are openly accessible.

bioinformatics↗

bioRxiv2025

On the typical development of the central sulcus in infancy: a longitudinal evaluation of its morphology and link to behaviour

IntroductionThe progressive folding of the cortex is an important feature of neurodevelopment starting early during gestation. The central sulcus (CS) is one of the first to fold. Since it represents the anatomical boundary between primary somatosensory and motor functional regions, its developing morphology may inform on the acquisition of sensorimotor skills. We aimed to identify potential asynchronous morphological changes along the CS during infancy, with the hypothesis that this may reflect the gradual emergence of body usage. MethodBased on 3T anatomical magnetic resonance imaging (MRI) and dedicated post-processing, we characterized the evolution in CS depth and curvature in 33 typical infants (aged 1 and 3 months, 22 with longitudinal data) in relation to 23 young adults as a reference. Four regions of interest (ROIs) along the CS, supposed to correspond to different parts of the body and one centred on the hand knob (HK), were reproducibly examined and compared across groups. We also explored the relationship between the age-related changes in morphological features and the global motor scaled scores evaluated at 3 months of age with the Bayley Scales of Infant and Toddler Development. ResultsWhile all ROIs showed significant increases in CS depth and curvature between 3-month-olds and adults, the results were more variable between 1 and 3 months of age depending on cross-sectional and longitudinal analyses. The central-medial and central-lateral regions showed the most consistent increase in depth. Besides, motor development at 3 months of age was not significantly related to CS morphological changes, but a positive trend was observed for depth changes in the (HK-related) central-medial ROI. ConclusionThe rapid evolution of CS folding during infancy may reflect the intense but asynchronous maturation of the brain sensorimotor system, with the differential growth of cortical areas related to body parts and underlying white matter connections. Although it will have to be replicated on larger groups and at other ages, this longitudinal and multimodal study highlights the potential of characterizing CS features as key markers of early sensorimotor development, both at the cerebral and behavioural levels. Combining anatomical and functional neuroimaging could provide deeper insights into the relationship between CS morphology and somatotopic organization in typical infants, but also in infants at risk of developing motor disorders.

neuroscience↗

bioRxiv2023

A bipolar taxonomy of adult human brain sulcal morphology related to timing of fetalsulcation and trans-sulcal gene expression gradients

We developed a computational pipeline (now provided as a resource) for measuring morphological similarity between cortical surface sulci to construct a sulcal phenotype network (SPN) from each magnetic resonance imaging (MRI) scan in an adult cohort (N=34,725; 45-82 years). Networks estimated from pairwise similarities of 40 sulci on 5 morphological metrics comprised two clusters of sulci, represented also by the bipolar distribution of sulci on a linear-to-complex dimension. Linear sulci were more heritable and typically located in unimodal cortex; complex sulci were less heritable and typically located in heteromodal cortex. Aligning these results with an independent fetal brain MRI cohort (N=228; 21-36 gestational weeks), we found that linear sulci formed earlier, and the earliest and latest-forming sulci had the least between-adult variation. Using high-resolution maps of cortical gene expression, we found that linear sulcation is mechanistically underpinned by trans-sulcal gene expression gradients enriched for developmental processes.

neuroscience↗

bioRxiv2022

Exploring the emergence of morphological asymmetries around the brain's Sylvian fissure: a longitudinal study of shape variability in preterm infants.

Brain folding patterns vary within the human species, but some folding properties are common across individuals, including the Sylvian fissures inter-hemispheric asymmetry. Contrarily to the other brain folds (sulci), the Sylvian fissure develops through the process of opercularization, with the frontal, parietal and temporal lobes growing over the insular lobe. Its asymmetry may be related to the leftward functional lateralization for language processing, but the time-course of these asymmetries development is still poorly understood. In this study, we investigated refined shape features of the Sylvian fissure and their longitudinal development in 71 infants born extremely preterm (mean gestational age at birth: 26.5 weeks) and imaged once before and once at term-equivalent age (TEA). We additionally assessed asymmetrical sulcal patterns at TEA in the perisylvian and inferior frontal regions, neighbor to the Sylvian fissure. While reproducing renown strong asymmetries in the Sylvian fissure, we captured an early encoding of its main asymmetrical shape features, and we observed global asymmetrical shape features representative of a more pronounced opercularization in the left-hemisphere, contrasting with the previously reported right-hemisphere advance in sulcation around birth. This added novel insights about the processes governing early-life brain folding mechanisms, potentially linked to the development of language-related capacities. Highlights- Shape features can be isolated to describe quantitatively the development of the Sylvian fissure - Strong asymmetries are encoded as soon as 30 weeks of post-menstrual age - The process of opercularization is more pronounced in the left hemisphere

neuroscience↗

bioRxiv2021

Shape variability of the central sulcus in the developing brain: a longitudinal descriptive and predictive study in preterm infants.

Despite growing evidence of links between sulcation and function in the adult brain, the folding dynamics, occurring mostly before normal-term-birth, is vastly unknown. Looking into the development of cortical sulci in babies can give us keys to address fundamental questions: what is the sulcal shape variability in the developing brain? When are the shape features encoded? How are these morphological parameters related to further functional development? In this study, we aimed to investigate the shape variability of the developing central sulcus, which is the frontier between the primary somatosensory and motor cortices. We studied a cohort of 71 extremely preterm infants scanned twice using MRI - once around 30 weeks post-menstrual age (w PMA) and once at term-equivalent age, around 40w PMA -, in order to quantify the sulcuss shape variability using manifold learning, regardless of age-group or hemisphere. We then used these shape descriptors to evaluate the sulcuss variability at both ages and to assess hemispheric and age- group specificities. This led us to propose a description of ten shape features capturing the variability in the central sulcus of preterm infants. Our results suggested that most of these features (8/10) are encoded as early as 30w PMA. We unprecedentedly observed hemispheric asymmetries at both ages, and the one captured at term-equivalent age seems to correspond with the asymmetry pattern previously reported in adults. We further trained classifiers in order to explore the predictive value of these shape features on manual performance at 5 years of age (handedness and fine motor outcome). The central sulcuss shape alone showed a limited but relevant predictive capacity in both cases. The study of sulcal shape features during early neurodevelopment may participate to a better comprehension of the complex links between morphological and functional organization of the developing brain. Highlights- Shape features can be isolated to describe quantitatively the development of the central sulcus. - Most shape characteristics of the central sulcus are already encoded at 30 weeks of post-menstrual age (w PMA) in preterm newborns. - The central sulcus shows subtle hemispheric asymmetries as soon as 30w PMA. - The early shape of the central sulcus can help predicting handedness and fine motor outcome at 5 years of age.

neuroscience↗

bioRxiv2021

Genetic variations within human gained enhancer elements affect human brain sulcal morphology.

The expansion of the cerebral cortex is one of the most distinctive changes in the evolution of the human brain. Cortical expansion and related increases in cortical folding may have contributed to emergence of our capacities for high-order cognitive abilities. Molecular analysis of humans, archaic hominins, and non-human primates has allowed identification of chromosomal regions showing evolutionary changes at different points of our phylogenetic history. In this study, we assessed the contributions of genomic annotations spanning 30 million years to human sulcal morphology measured via MRI in more than 18,000 participants from the UK Biobank. We found that variation within brain-expressed human gained enhancers, regulatory genetic elements that emerged since our last common ancestor with Old World monkeys, explained more trait heritability than expected for the left and right calloso-marginal posterior fissures and the right central sulcus. Intriguingly, these are sulci that have been previously linked to the evolution of locomotion in primates and later on bipedalism in our hominin ancestors.

neuroscience↗

bioRxiv2020

Genome-wide haplotype association study in imaging genetics using whole-brain sulcal openings of 16,304 UK Biobank subjects.

Neuroimaging-genetics cohorts gather two types of data: brain imaging and genetic data. They allow the discovery of associations between genetic variants and brain imaging features. They are invaluable resources to study the influence of genetics and environment in the brain features variance observed in normal and pathological populations. This study presents a genome wide haplotype analysis for 123 brain sulcus opening value (a measure of sulcal width) across the whole brain that include 16,304 subjects from UK Biobank. Using genetic maps, we defined 119,548 blocks of low recombination rate distributed along the 22 autosomal chromosomes, and analyzed 1,051,316 haplotypes. To test associations between haplotypes and complex traits, we designed three statistical approaches. Two of them use a model that includes all the haplotypes for a sin gle block, while the last approach considers one model by haplotype. All the statistics produced were assessed as rigorously as possible. Thanks to the rich imaging dataset at hand, we used resampling techniques to assess False Positive Rate for each statistical approach in a genome-wide and brain-wide context. The results on real data show that genome-wide haplotype analyses are more sensitive than single-SNP approach and account for local complex Linkage Disequilibrium (LD) structure, which makes genome-wide haplotype analysis an interesting and statistically sound alternative to the single-SNP counterpart.

bioinformatics↗

bioRxiv2019

The reliability and heritability of cortical folds and their genetic correlations across hemispheres.

The structure of the brains cortical folds varies considerably in human populations. Specific patterns of cortical variation arise with development and aging, and cortical traits are partially influenced by genetic factors. The degree to which genetic factors affect cortical folding patterning remains unknown, yet may be estimated with large-scale in-vivo brain MRI. Using multiple MRI datasets from around the world, we estimated the reliability and heritability of sulcal morphometric characteristics including length, depth, width, and surface area, for 61 sulci per hemisphere of the human brain. Reliability was assessed across four distinct test-retest datasets. We meta-analyzed the heritability across three independent family-based cohorts (N > 3,000), and one cohort of largely unrelated individuals (N~9,000) to examine the robustness of our findings. Reliability was high (interquartile range for ICC: 0.65-0.85) for sulcal metrics. Most sulcal measures were moderately to highly heritable (heritability estimates = 0.3-0.7). These genetic influences vary regionally, with the earlier forming sulci having higher heritability estimates. The central sulcus, the subcallosal and the collateral fissure were the most highly heritable regions. For some frontal and temporal sulci, left and right genetic influences did not completely overlap, suggesting some lateralization of genetic effects on the cortex.

genetics↗

bioRxiv2019

A DACT1 enhancer modulates brain asymmetric temporal regions involved in language processing

Identifying the genes that contribute to the variability in brain regions involved in language processing may shed light on the evolution of brain structures essential to the emergence of language in Homo sapiens. The superior temporal asymmetrical pit (STAP), which is not observed in chimpanzees, represents an ideal phenotype to investigate the genetic variations that support human communication. The left STAP depth was significantly associated with a predicted enhancer annotation located in the 14q23.1 locus, between DACT1 and KIAA0586, in the UK Biobank British discovery sample (N=16,515). This association was replicated in the IMAGEN cohort (N=1,726) and the UK Biobank non-British validation sample (N=2,161). This genomic region was also associated to a lesser extent with the right STAP depth and the formation of sulcal interruptions, plis de passage, in the bilateral STAP but not with other structural brain MRI phenotypes, highlighting its notable association with the superior temporal regions. Diffusion MRI emphasized an association with the fractional anisotropy of the left auditory fibers of the corpus callosum and with networks involved in linguistic processing in resting-state functional MRI. Overall, this evidence demonstrates a specific relationship between this locus and the establishment of the superior temporal regions that support human communication.

neuroscience↗

bioRxiv2019

Comparison between diffusion MRI tractography and histological tract-tracing of cortico-cortical structural connectivity in the ferret brain

The anatomical wiring of the brain is a central focus in network neuroscience. Diffusion MRI tractography offers the unique opportunity to investigate the brain fiber architecture in vivo and non invasively. However, its reliability is still highly debated. Here, we explored the ability of diffusion MRI tractography to match invasive anatomical tract-tracing connectivity data of the ferret brain. We also investigated the influence of several state-of-the-art tractography algorithms on this match to ground truth connectivity data. Tract-tracing connectivity data were obtained from retrograde tracer injections into the occipital, parietal and temporal cortices of adult ferrets. We found that the relative densities of projections identified from the anatomical experiments were highly correlated with the estimates from all the studied diffusion tractography algorithms (Spearmans rho ranging from 0.67 to 0.91), while only small, non-significant variations appeared across the tractography algorithms. These results are comparable to findings reported in mouse and monkey, increasing the confidence in diffusion MRI tractography results. Moreover, our results provide insights into the variations of sensitivity and specificity of the tractography algorithms and hence, into the influence of choosing one algorithm over another.

neuroscience↗

bioRxiv2018

A computational approach for characterizing the structural basis of intrinsic coupling modes of the cerebral cortex

Intrinsic coupling modes (ICMs) provide a framework for describing the interactions of ongoing brain activity at multiple spatial and temporal scales. Two families of ICMs can be distinguished: phase and envelope ICMs. The principles that shape these ICMs remain partly elusive, in particular their relation to the underlying brain structure. Here we explored structure-function relationships in the ferret brain between ICMs quantified from ongoing brain activity recorded with chronically implanted ECoG arrays and structural connectivity (SC) obtained from high-resolution diffusion MRI tractography. Large-scale computational models as well as simple topological ingredients of SC were used to explore the ability to predict both types of ICMs. Importantly, all investigations were conducted with ICM measures that are sensitive or insensitive to volume conduction effects. The results show that both types of ICMs are strongly related to SC, except when using ICM measures removing zero-lag synchronizations. Computational models are challenged to predict these ICM patterns consistently, and simple predictions from SC topological features can sometimes outperform them. Overall, the results demonstrate that patterns of cortical functional coupling as reflected in both phase and envelope ICMs bear a substantial relation to the underlying structural connectivity of the cerebral cortex.

neuroscience↗

bioRxiv2018

Increased and decreased superficial white matter structural connectivity in schizophrenia and bipolar disorder

Schizophrenia (SZ) and bipolar disorder (BD) are often conceptualized as \"disconnection syndromes\", with substantial evidence of abnormalities in deep white matter tracts, forming the substrates of long-range connectivity, seen in both disorders. However, the study of superficial white matter (SWM) U-shaped short-range tracts remained challenging until recently, although findings from post-mortem studies suggest they are likely integral components of SZ and BD neuropathology. This diffusion weighted imaging (DWI) study aimed to investigate SWM microstructure in vivo in both SZ and BD for the first time. We performed whole brain tractography in 31 people with SZ, 32 people with BD and 54 controls using BrainVISA and Connectomist 2.0. Segmentation and labelling of SWM tracts were performed using a novel, comprehensive U-fiber atlas. Analysis of covariances yielded significant generalized fractional anisotropy (gFA) differences for 17 SWM bundles in frontal, parietal and temporal cortices. Post hoc analyses showed gFA reductions in both patient groups as compared with controls in bundles connecting regions involved in language processing, mood regulation, working memory and motor function (pars opercularis, insula, anterior cingulate, precentral gyrus). We also found increased gFA in SZ patients in areas overlapping the default mode network (inferior parietal, middle temporal, precuneus), supporting functional hyperconnectivity of this network evidenced in SZ. We thus illustrate that short U-fibers are vulnerable to the pathological processes in major psychiatric illnesses, encouraging improved understanding of their anatomy and function.

neuroscience↗

bioRxiv2018

Analysis of brain network dynamics estimated from fMRI data: A new framework based on communicability and flow

Neuroimaging techniques such as MRI have been widely used to explore the associations between brain areas. Structural connectivity (SC) captures the anatomical pathways across the brain and functional connectivity (FC) measures the correlation between the activity of brain regions. These connectivity measures have been much studied using network theory in order to uncover the distributed organization of brain structures, in particular FC for task-specific brain communication. However, the application of network theory to study FC matrices is often "static" despite the dynamic nature of time series obtained from fMRI. The present study aims to overcome this limitation by introducing a network-oriented analysis applied to whole-brain effective connectivity (EC) useful to interpret the brain dynamics. Technically, we tune a multivariate Ornstein-Uhlenbeck (MOU) process to reproduce the statistics of the whole-brain resting-state fMRI signals, which provides estimates for MOU-EC as well as input properties (similar to local excitabilities). The network analysis is then based on the Green function (or network impulse response) that describes the interactions between nodes across time for the estimated dynamics. This model-based approach provides time-dependent graph-like descriptor, named communicability, that characterize the roles that either nodes or connections play in the propagation of activity within the network. They can be used at both global and local levels, and also enables the comparison of estimates from real data with surrogates (e.g. random network or ring lattice). In contrast to classical graph approaches to study SC or FC, our framework stresses the importance of taking the temporal aspect of fMRI signals into account. Our results show a merging of functional communities over time (in which input properties play a role), moving from segregated to global integration of the network activity. Our formalism sets a solid ground for the analysis and interpretation of fMRI data, including task-evoked activity.

neuroscience↗

bioRxiv2018

eQTL of KCNK2 regionally influences the brain sulcal widening: evidence from 15,597 UK Biobank participants with neuroimaging data

The grey and white matter volumes are known to reduce with age. This cortical shrinkage is visible on magnetic resonance images and is conveniently identified by the increased volume of cerebrospinal fluid in the sulci between two gyri. Here, we replicated this finding using the UK Biobank dataset and studied the genetic influence on these cortical features of aging. We divided all individuals genetically confirmed of British ancestry into two sub-cohorts (12,162 and 3,435 subjects for discovery and replication samples, respectively). We found that the heritability of the sulcal opening ranges from 15 to 45% (s.e.= 4.8%). We identified 4 new loci that contribute to this opening, including one that also affects the sulci grey matter thickness. We identified the most significant variant (rs864736) on this locus as being an expression quantitative trait locus (eQTL) for the KCNK2 gene. This gene regulates the immune-cell into the central nervous system (CNS) and controls the CNS inflammation, which is implicated in cortical atrophy and cognitive decline. These results expand our knowledge of the genetic contribution to cortical shrinking and promote further investigation into these variants and genes in pathological context such as Alzheimers disease in which brain shrinkage is a key biomarker.

genetics↗