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Auzias, G.

Publications and source records attributed to Auzias, G..

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Data quality biases normative models derived from fetal brain MRI

Normative modeling is increasingly used to characterize typical growth trajectories and identify atypical neurodevelopment, including early brain development using magnetic resonance imaging (MRI) acquired before birth. Recent work has emphasized the importance of large sample sizes for accurate and robust centile estimation. In this study, we investigate how image quality influences fetal brain normative models, a critical factor in this context where MRI is acquired on a moving fetus in utero. Using a multi-centric cohort of 635 fetal MRI scans, we applied a standardized visual quality control (QC) protocol with continuous quality ratings. We fit normative models for multiple brain structures under progressively relaxed QC stringency, and quantified the deviations in centile estimates relative to a high-quality reference subgroup. Our results showed that including lower-quality data systematically biased normative centiles, with the strongest effects observed in the outer centiles, particularly the lower tail (1st-10th). Bias increased progressively as QC stringency was relaxed and could not be attributed solely to the number of subjects used to fit the models. Quality-induced bias was structure-dependent, and often not visually apparent at the segmentation level. These findings highlight that image quality is an important source of bias in normative fetal brain modeling, and that increasing sample size at the expense of quality may systematically affect centile estimates, potentially jeopardizing the utility of the model.

neuroscience↗

Differential microstructural development within sensorimotor cortical regions: A diffusion MRI study in preterm and full-term infants

The sensorimotor system develops early in utero and supports the emergence of body representations critical for perception, action, and interaction with environment. While somatotopic protomaps are already developed in the primary somatosensory and motor cortices in late pregnancy, little is known about the anatomical substrates of this functional specialization. In this study, we aimed to decipher the microstructural properties of these regions in the developing brain. Using advanced diffusion MRI and post-processing tools, we parcellated the pre- and post-central gyri into microstructurally distinct clusters along the lateral-to-medial axis in full-term neonates, confirming the early differentiation within sensorimotor regions. These clusters were further analyzed in preterm infants scanned near birth and at term-equivalent age (TEA), compared with another group of full-term neonates. Applying a multivariate Mahalanobis distance approach, we quantified deviations in preterm cortical microstructure relative to the full-term reference. Preterm infants showed significant region- and position-specific deviations at both ages, though these were smaller at TEA, consistently with ongoing maturation during the pre-term period. Differences between the pre- and post-central gyri, and along the somatotopic axis, suggested differential vulnerability to prematurity. In particular, the motor regions appeared to be at a more advanced stage of maturation close to birth and less vulnerable at TEA than somatosensory regions. An opposite trend was observed for lateral positions related to mouth representation compared with intermediary and medial positions. These findings support the notion that early sensorimotor cortical specialization is microstructurally emergent during gestation and sensitive to atypical developmental context of preterm birth.

neuroscience↗

Higher-order and distributed synergistic functional interactions encode information gain in goal-directed learning

Goal-directed learning arises from distributed neural circuits including the prefrontal, posterior parietal and temporal cortices. However, the role of cortico-cortical functional interactions remains unclear. To address this question, we integrated information dynamics analysis with magnetoencephalography to investigate the encoding of learning signals through neural interactions. Our findings revealed that information gain (the reduction in uncertainty about the causal relationship between actions and outcomes) is represented over the visual, parietal, lateral prefrontal and ventromedial/orbital prefrontal cortices. Cortico-cortical interactions encoded information gain synergistically at the level of pairwise and higher-order relations, such as triplets and quadruplets. Higher-order synergistic interactions were characterized by long-range relationships centered in the ventromedial and orbitofrontal cortices, which served as key receivers in the broadcast of information gain across cortical circuits. Overall, this study provides evidence that information gain is encoded through synergistic and higher-order functional interactions and is broadcast to prefrontal reward circuits.

neuroscience↗

Assessing data quality on fetal brain MRI reconstruction: a multi-site and multi-rater study

Quality assessment (QA) has long been considered essential to guarantee the reliability of neuroimaging studies. It is particularly important for fetal brain MRI, where unpredictable fetal motion can lead to substantial artifacts in the acquired images. Multiple images are then combined into a single volume through super-resolution reconstruction (SRR) pipelines, a step that can also introduce additional artifacts. While multiple studies designed automated quality control pipelines, no work evaluated the reproducibility of the manual quality ratings used to train these pipelines. In this work, our objective is twofold. First, we assess the inter- and intra-rater variability of the quality scoring performed by three experts on over 100 SRR images reconstructed using three different SRR pipelines. The raters were asked to assess the quality of images following 8 specific criteria like blurring or tissue contrast, providing a multi-dimensional view on image quality. We show that, using a protocol and training sessions, artifacts like bias field and blur level still have a low agreement (ICC below 0.5), while global quality scores show very high agreement (ICC = 0.9) across raters. We also observe that the SRR methods are influenced differently by factors like gestational age, input data quality and number of stacks used by reconstruction. Finally, our quality scores allow us to unveil systematic weaknesses of the different pipelines, indicating how further development could lead to more robust, well rounded SRR methods. Our rating protocol is made available at https://doi.org/10.5281/zenodo.15696638.

neuroscience↗

Normative models combining fetal and postnatal MRI data to characterize neurodevelopmental trajectories during the transition from in- to ex-utero

The perinatal period involves transitioning from an intra- to an extrauterine environment, which requires a complex adaptation of the brain. This period is marked with dynamic and multifaceted cortical changes in both structure and function. Most studies to date have focused either on the fetal or postnatal period, independently. To the best of our knowledge, this is the first neurodevelopmental study targeting the cortical trajectory of typically developing perinatal subjects, combining MRIs from both fetal and postnatal participants. Prior to analysis, preprocessing and segmentation parameters were harmonized across all subjects in order to overcome methodological limitations that arise when studying such different populations. We conducted a normative modeling analysis on a sample of 607 subjects, age ranged 24 to 45 weeks post-conception, to observe changes that arise as participants traverse the birth barrier. We observed that the trajectories of global surface area and several volumetric features, including total gray matter, white matter, brainstem, cerebellum and hippocampi, follow distinct but continuous patterns during this transition. We further report three features presenting a discontinuity in their neurodevelopmental trajectories as participants traverse from a fetal to a postnatal environment: the extra-cerebrospinal fluid volume, the ventricular volume and global gyrification. The current study demonstrates the presence of unique neurodevelopmental patterns for several structural features during the perinatal period, and confirms that not all features are affected in the same way as they cross the birth barrier. SIGNIFICANCE STATEMENTThe perinatal phase comprises the fetal and immediate postnatal period, and is generally described as the time surrounding birth. Comprehensively understanding this period is crucial due to the presence of dynamic and multifaceted brain changes. What makes this investigation unique is that it is the first neurodevelopmental study, to the best of our knowledge, focused on the cortical trajectory of typically developing perinatal subjects through the combination of both fetal and postnatal participants into one analysis. We report that certain brain feature trajectories change drastically as fetuses become newborns, while other features remain continuous. These observations are relevant in both the isolation of biomarkers for later cognitive and physiological disorders and in the understanding of typical cerebral development.

neuroscience↗

Subtly altered topological asymmetry of brain structural covariance networks in autism spectrum disorder across 43 datasets from the ENIGMA consortium

Small average differences in the left-right asymmetry of cerebral cortical thickness have been reported in individuals with autism spectrum disorder (ASD) compared to typically developing controls. Although these alterations affect multiple and widespread cortical regional asymmetries, the extent to which specific structural networks might be affected remains unknown. Inter-regional morphological covariance analysis can capture network connectivity relations between different cortical areas at the macroscale level. Here, we used cortical thickness data from 1,455 individuals with ASD and 1,560 controls, across 43 independent datasets of the ENIGMA consortiums ASD Working Group, to assess hemispheric asymmetries of intra-individual structural covariance networks, using graph theory-based topological metrics. Compared with typical features of small-world architecture in controls, the ASD sample showed significantly altered asymmetry of hemispheric networks involving the fusiform, rostral middle frontal, and medial orbitofrontal cortex, driven by shifts toward higher randomization of the corresponding right-hemispheric networks in ASD. A network involving the superior frontal cortex showed decreased right-hemisphere randomization. Based on comparisons with meta-analyzed functional neuroimaging data, the altered connectivity asymmetry particularly affected networks that subserve working memory, executive functions, language, reading, and sensorimotor processes. Taken together, these findings provide new insights into how altered brain left-right asymmetry in ASD affects specific structural and functional brain networks. Altered asymmetrical brain development in ASD may be partly propagated among spatially distant regions through structural connectivity.

neuroscience↗

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↗

Altered structural brain asymmetry in autism spectrum disorder: large-scale analysis via the ENIGMA Consortium

BackgroundLeft-right asymmetry is an important organizing feature of the healthy brain. Various studies have reported altered structural brain asymmetry in autism spectrum disorder (ASD). However, findings have been inconsistent, likely due to limited sample sizes and low statistical power.\n\nMethodsWe investigated 1,774 subjects with ASD and 1,809 controls, from 54 datasets, for differences in the asymmetry of thickness and surface area of 34 cerebral cortical regions. We also examined global hemispheric measures of cortical thickness and area asymmetry, and volumetric asymmetries of subcortical structures. Data were obtained via the ASD Working Group of the ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) consortium. T1-weighted MRI data were processed with a single protocol using FreeSurfer and the Desikan-Killiany atlas.\n\nResultsASD was significantly associated with reduced leftward asymmetry of total hemispheric average cortical thickness, compared to controls. Eight regional thickness asymmetries, distributed over the cortex, also showed significant associations with diagnosis after correction for multiple comparisons, for which asymmetry was again generally lower in ASD versus controls. In addition, the medial orbitofrontal surface area was less rightward asymmetric in ASD than controls, and the putamen volume was more leftward asymmetric in ASD than controls. The largest effect size had Cohens d = 0.15. Most effects did not depend on age, sex, IQ, or disorder severity.\n\nConclusionAltered lateralized neurodevelopment is suggested in ASD, affecting widespread cortical regions with diverse functions. Large-scale analysis was necessary to reliably detect, and accurately describe, subtle alterations of structural brain asymmetry in this disorder.

neuroscience↗

SPANOL (SPectral ANalysis Of Lobes): A spectral clustering framework for individual and group parcellation of cortical surfaces in lobes

Understanding the link between structure, function and development in the brain is a key topic in neuroimaging that benefits from the tremendous progress of multi-modal MRI and its computational analysis. It implies, inter alia, to be able to parcellate the brain volume or cortical surface into biologically relevant regions. These parcellations may be inferred from existing atlases (e.g. Desikan) or sets of rules, as would do a neuroanatomist for lobes, but also directly driven from the data (e.g. functional or structural connectivity) with minimum a priori. In the present work, we aimed at using the intrinsic geometric information contained in the eigenfunctions of Laplace-Beltrami Operator to obtain parcellations of the cortical surface based only on its description by triangular meshes. We proposed a framework adapted from spectral clustering, general in scope and suitable for the co-parcellation of a group of subjects. We applied it to a dataset of 62 adults, optimized it and revealed a striking agreement between parcels produced by this unsupervised clustering and Freesurfer lobes (Desikan atlas), which cannot be explained by chance. Already suitable by itself, this spectral analysis of lobes (Spanol) could conveniently be fitted into a multimodal pipeline for optimized and fast lobar segmentation. Eventually, we showed promising results of Spanol on smoother brains and notably on a dataset of 15 fetuses, with an interest for both the understanding of cortical ontogeny and the applicative field of perinatal computational neuroanatomy.

neuroscience↗