Biology subjects

Crivello, F.

Publications and source records attributed to Crivello, F..

15 recordsLinked to original sources

bioRxiv2025

Resting State connectivity patterns associated with trait anxiety in adolescence

Anxiety symptoms can vary across different life stages, with a higher frequency during adolescence and early adulthood, increasing the risk of developing future anxiety disorders. To date, neuroscientific research on anxiety has primarily focused on adulthood, thus limiting our understanding of how anxiety may characterize earlier stages of life, and employing mostly univariate approaches, thus discounting large-scale alterations of the brain. One intriguing hypothesis is that adolescents with trait anxiety may display similar abnormalities shown by adults in brain regions ascribed to the Default Mode Network (DMN) associated with self-referential thinking, awareness, and rumination-related processes. The present study aims to expand our previous knowledge on this topic using a large sample of young individuals to uncover the resting-state connectivity patterns associated with trait anxiety in a network approach. To test our hypotheses, we analyzed the rs-fMRI images of 1263 adolescents (mean age 20.55 years) as well as their scores on anxiety trait. A significant association between trait anxiety and resting-state functional connectivity in two networks was found, with some regions overlapping with the Default Mode Network. The first network included regions such as the cingulate gyrus and the middle temporal gyri known to be involved in self-referential processing and emotional perception and control, both altered in anxiety disorders. The second network included the precuneus, possibly related to rumination that characterizes anxiety. Of note, the higher the trait anxiety, the lower the connectivity within both networks, suggesting abnormal self-referential processing, awareness, and emotion regulation abilities in adolescents with high anxiety trait. These findings provided a better understanding of the association between trait anxiety and brain rs-functional connectivity, and may pave the way for the development of potential biomarkers in adolescents with anxiety.

neuroscience↗

bioRxiv2023

Normative Modeling of Brain Morphometry Across the Lifespan using CentileBrain: Algorithm Benchmarking and Model Optimization

We present an empirically benchmarked framework for sex-specific normative modeling of brain morphometry that can inform about the biological and behavioral significance of deviations from typical age-related neuroanatomical changes and support future study designs. This framework was developed using regional morphometric data from 37,407 healthy individuals (53% female; aged 3-90 years) following a comparative evaluation of eight algorithms and multiple covariate combinations pertaining to image acquisition and quality, parcellation software versions, global neuroimaging measures, and longitudinal stability. The Multivariate Factorial Polynomial Regression (MFPR) emerged as the preferred algorithm optimized using nonlinear polynomials for age and linear effects of global measures as covariates. The MFPR models showed excellent accuracy across the lifespan and within distinct age-bins, and longitudinal stability over a 2-year period. The performance of all MFPR models plateaued at sample sizes exceeding 3,000 study participants. The model and scripts described here are freely available through CentileBrain (https://centilebrain.org/).

bioinformatics↗

bioRxiv2022

Dissociable Cellular and Genetic Mechanisms of Cortical Thinning at Different Life Stages

Mechanisms underpinning age-related variations in cortical thickness in the human brain remain poorly understood. We investigated whether inter-regional age-related variations in cortical thinning (in a multicohort neuroimaging dataset from the ENIGMA Lifespan Working Group totalling 14,248 individuals, aged 4-89 years) depended on cell-specific marker gene expression levels. We found differences amidst early-life (<20 years), mid-life (20-60 years), and late-life (>60 years) in the patterns of association between inter-regional profiles of cortical thickness and expression profiles of marker genes for CA1 and S1 pyramidal cells, astrocytes, and microglia. Gene ontology and enrichment analyses indicated that each of the three life-stages was associated with different biological processes and cellular components: synaptic modeling in early life, neurotransmission in mid-life, and neurodegeneration in late-life. These findings provide mechanistic insights into age-related cortical thinning during typical development and aging.

neuroscience↗

bioRxiv2021

Left-handedness and its genetic influences are associated with structural asymmetries mapped across the cerebral cortex in 31,864 individuals

Roughly 10% of the human population is left-handed, and this rate is increased in some brain-related disorders. The neuroanatomical correlates of hand preference have remained equivocal. We re-sampled structural brain image data from 28,802 right-handers and 3,062 left-handers (UK Biobank population dataset) to a symmetrical surface template, and mapped asymmetries for each of 8,681 vertices across the cerebral cortex in each individual. Left-handers and right-handers showed average differences of surface area asymmetry within fusiform, anterior insular, anterior-middle-cingulate and precentral cortex. Meta-analyzed functional imaging data implicated these regions in executive functions and language. Polygenic disposition to left-handedness was associated with two of these regional asymmetries, and 18 loci previously linked with left-handedness by genome-wide screening showed associations with one or more of these asymmetries. Implicated genes included six encoding microtubule-related proteins: TUBB, TUBA1B, TUBB3, TUBB4A, MAP2 and NME7 - the latter is mutated in left-right reversal of the visceral organs. There were also two cortical regions where average thickness asymmetry was altered in left-handedness: on the postcentral gyrus and inferior occipital cortex, functionally annotated with hand sensorimotor and visual roles. These cortical thickness asymmetries were not heritable. Heritable surface area asymmetries of language-related regions may link the etiologies of hand preference and language, whereas non-heritable asymmetries of sensorimotor cortex may manifest as consequences of hand preference.

neuroscience↗

bioRxiv2021

Brain charts for the human lifespan

Over the past few decades, neuroimaging has become a ubiquitous tool in basic research and clinical studies of the human brain. However, no reference standards currently exist to quantify individual differences in neuroimaging metrics over time, in contrast to growth charts for anthropometric traits such as height and weight1. Here, we built an interactive resource to benchmark brain morphology, www.brainchart.io, derived from any current or future sample of magnetic resonance imaging (MRI) data. With the goal of basing these reference charts on the largest and most inclusive dataset available, we aggregated 123,984 MRI scans from 101,457 participants aged from 115 days post-conception through 100 postnatal years, across more than 100 primary research studies. Cerebrum tissue volumes and other global or regional MRI metrics were quantified by centile scores, relative to non-linear trajectories2 of brain structural changes, and rates of change, over the lifespan. Brain charts identified previously unreported neurodevelopmental milestones3; showed high stability of individual centile scores over longitudinal assessments; and demonstrated robustness to technical and methodological differences between primary studies. Centile scores showed increased heritability compared to non-centiled MRI phenotypes, and provided a standardised measure of atypical brain structure that revealed patterns of neuroanatomical variation across neurological and psychiatric disorders. In sum, brain charts are an essential first step towards robust quantification of individual deviations from normative trajectories in multiple, commonly-used neuroimaging phenotypes. Our collaborative study proves the principle that brain charts are achievable on a global scale over the entire lifespan, and applicable to analysis of diverse developmental and clinical effects on human brain structure. Furthermore, we provide open resources to support future advances towards adoption of brain charts as standards for quantitative benchmarking of typical or atypical brain MRI scans.

neuroscience↗

bioRxiv2021

Changes in regional white matter volumetry and microstructure during the post-adolescence period: a cross-sectional study of a cohort of 1,713 university students

Human brain white matter undergoes a protracted maturation that continues well into adulthood. Recent advances in diffusion-weighted imaging (DWI) methods allow detailed characterizations of the microstructural architecture of white matter, and they are increasingly utilised to study white matter changes during development and ageing. However, relatively little is known about the late maturational changes in the microstructural architecture of white matter during post-adolescence. Here we report on regional changes in white matter volume and microstructure in young adults undergoing university-level education. As part of the MRi-Share multi-modal brain MRI database, multi-shell, high angular resolution DWI data were acquired in a unique sample of 1,713 university students aged 18 to 26. We assessed the age and sex dependence, as well as hemispheric asymmetry of diffusion metrics derived from diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI), in the white matter regions as defined in the John Hopkins University (JHU) white matter labels atlas. We demonstrate that while regional white matter volume is relatively stable over the age range of our sample, the white matter microstructural properties show clear age-related variations. Globally, it is characterised by a robust increase in neurite density index (NDI), and to a lesser extent, orientation dispersion index (ODI). These changes are accompanied by a decrease in diffusivity. In contrast, there is minimal age-related variation in fractional anisotropy. There are regional variations in these microstructural changes: some tracts, most notably cingulum bundles, show a strong age-related increase in NDI coupled with decreases in radial and mean diffusivity, while others, mainly cortico-spinal projection tracts, primarily show an ODI increase and axial diffusivity decrease. These age-related variations are not different between males and females, but males show higher NDI and ODI and lower diffusivity than females across many tracts. We also report a robust hemispheric asymmetry in both the volume and microstructural properties in many regions. These findings emphasise the complexity of changes in white matter structure occurring in this critical period of late maturation in early adulthood.

neuroscience↗

bioRxiv2021

Characterization of late structural maturation with a neuroanatomical marker that considers both cortical thickness and intracortical myelination

The cortical ribbon changes throughout a persons lifespan, with the most significant changes occurring during crucial development and aging periods. Changes during adulthood are rarely investigated due to the scarcity of neuroimaging data during this period. After childhood, the brain loses gray matter, which is evidenced by an apparent reduction in cortical thickness (CT); one factor of this thinning process is intense ongoing intracortical myelination (MYEL). Here, we report age-related changes in CT, MYEL, and their ratio in 447 participants aged 18 to 57 years (BIL&GIN cohort). We propose the CT/MYEL ratio to be a multimodal cortical maturation index (MATUR) capable of reflecting 1) stages during which CT and MYEL patterns diverge and 2) the regional differences in cortical maturation that occur in adulthood. Age mainly decreased CT in all cortical regions, with larger reductions occurring in the bilateral insular lobes, temporal and frontal poles, and cingulate cortices. Age led to a linear increase in MYEL in the entire cortex and larger increases in the primary motor, auditory, and visual cortices. The effects of age on the MATUR index were characterized by both linear and quadratic components. The linear component mimicked the pattern found in CT, with 1) a robust amplification of the global and regional effects of age on CT and 2) evidence of new bilateral linear decreases in the frontal and cortical cortices. Most importantly, age exhibited additional large quadratic effects on the MATUR index in the bilateral frontal (more prominent in the right hemisphere), parietal, temporal, and cingulate regions that were not highlighted by the CT metric. Thus, the MATUR index was more sensitive to age-related cortical structural changes during adulthood than was either CT or MYEL alone. As evidenced by the large quadratic component of the effect of age, the newly proposed maturation index dramatically improved the characterization of the regional cortical territories, uncovering the latest brain maturation steps that occur before stabilization and deterioration occur in mid- and late adulthood.

neuroscience↗

bioRxiv2020

The genetic architecture of structural left-right asymmetry of the human brain

Left-right hemispheric asymmetry is an important aspect of healthy brain organization for many functions including language, and can be altered in cognitive and psychiatric disorders1-8. No mechanism has yet been identified for establishing the human brains left-right axis9. We performed multivariate genome-wide association scanning (mvGWAS) of cortical regional surface area and thickness asymmetries, and subcortical volume asymmetries, using data from 32,256 participants from the UK Biobank. There were 21 significant loci affecting different aspects of brain asymmetry, with functional enrichment involving microtubule-related genes and embryonic brain expression. These findings are consistent with a known role of the cytoskeleton in left-right axis determination in other organs of invertebrates and frogs10-12. Genetic variants affecting brain asymmetry overlapped with those influencing autism, educational attainment and schizophrenia.

neuroscience↗

bioRxiv2020

The MRi-Share database: brain imaging in a cross-sectional cohort of 1,870 university students

We report on MRi-Share, a multi-modal brain MRI database acquired in a unique sample of 1,870 young healthy adults, aged 18 to 35 years, while undergoing university-level education. MRi-Share contains structural (T1 and FLAIR), diffusion (multispectral), susceptibility weighted (SWI), and resting-state functional imaging modalities. Here, we described the contents of these different neuroimaging datasets and the processing pipelines used to derive brain phenotypes, as well as how quality control was assessed. In addition, we present preliminary results on associations of some of these brain image-derived phenotypes at the whole brain level with both age and sex, in the subsample of 1,722 individuals aged less than 26 years. We demonstrate that the post-adolescence period is characterized by changes in both structural and microstructural brain phenotypes. Grey matter cortical thickness, surface area and volume were found to decrease with age, while white matter volume shows increase. Diffusivity, either radial or axial, was found to robustly decrease with age whereas fractional anisotropy only slightly increased. As for the neurite orientation dispersion and densities, both were found to increase with age. The isotropic volume fraction also showed a slight increase with age. These preliminary findings emphasize the complexity of changes in brain structure and function occurring in this critical period at the interface of late maturation and early aging.

neuroscience↗

bioRxiv2020

Typical and atypical language brain organization based on intrinsic connectivity and multitask functional asymmetries

Based on the joint investigation in 287 healthy volunteers (150 Left-Handers (LH)) of language task-induced asymmetries and intrinsic connectivity strength of the sentence-processing supramodal network, we show that individuals with atypical rightward language lateralization (N = 30, 25 LH) do not rely on an organization that simply mirrors that of typical leftward lateralized individuals. Actually, the resting-state organization in the atypicals showed that their sentence processing was underpinned by left and right networks both wired for language processing and highly interacting by strong interhemispheric intrinsic connectivity and larger corpus callosum volume. Such a loose hemispheric specialization for language permits the hosting of language in either the left and/or right hemisphere as assessed by a very high incidence of dissociations across various language task-induced asymmetries in this group.

neuroscience↗

bioRxiv2020

Greater male than female variability in regional brain structure across the lifespan

For many traits, males show greater variability than females, with possible implications for understanding sex differences in health and disease. Here, the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Consortium presents the largest-ever mega-analysis of sex differences in variability of brain structure, based on international data spanning nine decades of life. Subcortical volumes, cortical surface area and cortical thickness were assessed in MRI data of 16,683 healthy individuals 1-90 years old (47% females). We observed significant patterns of greater male than female between-subject variance for all subcortical volumetric measures, all cortical surface area measures, and 60% of cortical thickness measures. This pattern was stable across the lifespan for 50% of the subcortical structures, 70% of the regional area measures, and nearly all regions for thickness. Our findings that these sex differences are present in childhood implicate early life genetic or gene-environment interaction mechanisms. The findings highlight the importance of individual differences within the sexes, that may underpin sex-specific vulnerability to disorders.

neuroscience↗

bioRxiv2019

Handedness and Other Variables Associated with Human Brain Asymmetrical Skew

The human cerebral hemispheres show a left-right asymmetrical torque pattern, which has been claimed to be absent in chimpanzees. The functional significance and developmental mechanisms are unknown. Here we carried out the largest-ever analysis of global brain shape asymmetry in magnetic resonance imaging data. Three population datasets were used, the UK Biobank (N = 39,678), Human Connectome Project (N = 1,113) and BIL&GIN (N = 453). At the population level, there was an anterior and dorsal skew of the right hemisphere, relative to the left. Both skews were associated independently with handedness, and various regional grey and white matter metrics oppositely in the two hemispheres, as well as other variables related to cognitive functions, sociodemographic factors, and physical and mental health. The two skews showed SNP-based heritabilities of 4-13%, but also substantial polygenicity in causal mixture model analysis, and no individually significant loci were found in GWAS for either skew. There was evidence for a significant genetic correlation (rg=-0.40, p=0.0075) between horizontal brain skew and Autism Spectrum Disorder. These results provide the first large-scale description of population-average brain skews and their inter-individual variations, their replicable associations with handedness, and insights into biological and other factors which associate with human brain asymmetry.

neuroscience↗

bioRxiv2019

Genetic effects on planum temporale asymmetry and their limited relevance to neurodevelopmental disorders, intelligence or educational attainment

Previous studies have suggested that altered asymmetry of the planum temporale (PT) is associated with neurodevelopmental disorders, including dyslexia, schizophrenia, and autism. Shared genetic factors have been suggested to link PT asymmetry to these disorders. In a dataset of unrelated subjects from the general population (UK Biobank, N= 18,057), we found that PT volume asymmetry had a significant heritability of roughly 14%. In genome-wide association analysis, two loci were significantly associated with PT asymmetry, including a coding polymorphism within the gene ITIH5 that is predicted to affect the proteins function and to be deleterious (rs41298373, P=2.01x10-15), and a locus that affects the expression of the genes BOK and DTYMK (rs7420166, P=7.54x10-10). DTYMK showed left-right asymmetry of mRNA expression in post mortem PT tissue. Cortex-wide mapping of these SNP effects revealed influences on asymmetry that went somewhat beyond the PT. Using publicly available genome-wide association statistics from large-scale studies, we saw no significant genetic correlations of PT asymmetry with autism spectrum disorder, attention deficit hyperactivity disorder, schizophrenia, educational attainment or intelligence. Of the top two individual loci associated with PT asymmetry, rs41298373 showed a tentative association with intelligence (unadjusted P=0.025), while the locus at BOK/DTYMK showed tentative association with educational attainment (unadjusted Ps<0.05). These findings provide novel insights into the genetic contributions to human brain asymmetry, but do not support a substantial polygenic association of PT asymmetry with cognitive variation and mental disorders, as far as can be discerned with current sample sizes.

genetics↗

bioRxiv2018

FALCON: a Functional Atlas of Language COmprehension Networks based on multiple task-induced activation mapping and graph analysis of intrinsic connectivity in 137 healthy right-handers

We herein propose an atlas of 32 sentence-related areas based on a 3-step method combining the analysis of activation and asymmetry during multiple language tasks with hierarchical clustering of resting-state connectivity and graph analyses. 144 healthy right-handers performed fMRI runs based on language production, reading and listening, both with sentences and lists of over-learned words. Sentence minus word-list BOLD contrast and left-minus-right BOLD asymmetry for each task were computed in pairs of homotopic regions of interest (hROIs) from the AICHA atlas. Thirty-two hROIs were identified that were conjointly activated and leftward asymmetrical in each of the 3 language contrasts. Analysis of resting- state temporal correlations of BOLD variations between these 32 hROIs allowed the segregation of a core network, SENT_CORE including 18 hROIs. Resting-state graph analysis applied to SENT_CORE hROIs revealed that the pars triangularis of the inferior frontal gyrus and the superior temporal sulcus were hubs based on their degree centrality, betweenness, and participation values, corresponding to epicentres of sentence processing. Positive correlations between DC and BOLD activation values for SENT_CORE hROIs were observed across individuals and across regions regardless of the task: the more a SENT_CORE area is connected at rest the stronger it is activated during sentence processing. DC measurements in SENT_CORE may thus be a valuable index for the evaluation of inter-individual variations in language areas functional activity in relation to anatomical or clinical patterns in large populations. SENSAAS (SENtence Supramodal Areas AtlaS), comprising the 32 supramodal sentence areas, including SENT-CORE network, can be downloaded at http://www.gin.cnrs.fr/en/tools/.

neuroscience↗

bioRxiv2018

A probabilistic atlas of the human pyramidal tract in 410 healthy participants

With the advances in diffusion MRI and tractography, numerous atlases of the human pyramidal tract (PyT) have been proposed but the inherent limitation of tractography to resolve crossing bundles within the centrum semiovale have so far prevented the complete description of the most lateral PyT projections. Here, we combined a precise manual positioning of individual subcortical regions of interest along the descending pathway of the PyT with a new bundle-specific tractography algorithm. This later is based on anatomical priors to improve streamlines tracking in crossing areas. We then extracted both left and right PyT in a large cohort of 410 healthy participants and built a population-based atlas of the whole-fanning PyT with a complete description of its most cortico-lateral projections. Clinical applications are envisaged, the whole-fanning PyT atlas being likely a better marker of corticospinal integrity metrics than those currently used within the frame of prediction of post-stroke motor recovery. The present population-based PyT, freely available, provides an interesting tool for clinical applications in order to locate specific PyT damage and its impact to the short and long-term motor recovery after stroke.

neuroscience↗