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Lemaitre, H.

Publications and source records attributed to Lemaitre, H..

At least 19 recordsLinked to original sources

Adversity and adolescent brain development: differential associations with grey and white matter across two longitudinal cohorts

Globally, 60% of the population has experienced at least one type of adversity (e.g., emotional abuse, bullying) across infancy, childhood, and adolescence. Such experiences have been linked to an increased risk for mental health disorders. Changes in brain structure following experiences of childhood adversity have been hypothesised to be a mechanistic pathway explaining later mental health issues. However, to understand how changes in brain structure might mediate the effects of adversity, it is essential to identify which underlying neuronal processes may be affected by different types of adverse experiences. A key open question is whether grey or white matter is more vulnerable to adversity, as these two structures reflect distinct neurobiological mechanisms. This study investigated whether differences in trajectories of grey and white matter development during adolescence can be explained by exposure to different types of adversity. We applied the Adverse Adolescent Experiences Framework (Pollmann et al., 2025) categorising adversity into four levels: Intrapersonal (e.g., accidents), Caregiver (e.g., emotional neglect), Peer (e.g., bullying), and Community (e.g., neighbourhood safety). Exposure to each of the four factors was estimated through principal components analyses. We analysed two large longitudinal datasets: the Adolescent Brain Cognitive Development study ([~]12,000 adolescents measured at ages 10, 12, and 14) and the IMAGEN study ([~]1,400 adolescents measured at ages 14, 19, and 22). Using latent growth curve models, we captured individual differences in brain development by estimating baseline levels (intercepts) and rates of change (slopes) for total grey matter volume and mean white matter fractional anisotropy. In both cohorts, we found significant interindividual variability in baseline levels and rates of change for both grey matter volume and fractional anisotropy. Caregiver, Peer, and Community adversities were negatively associated only with the intercepts of grey matter volume and white matter fractional anisotropy. Importantly, associations differed between grey and white matter. In ABCD, Peer and Community adversities were more strongly associated with grey matter volume intercepts. In contrast, in IMAGEN, Caregiver, Peer and Community adversities were more strongly linked to white matter fractional anisotropy intercepts. This suggests that adversity has unique associations with grey and white matter, rather than exerting a uniform influence on brain structure. By demonstrating that different environments generate distinct biological associations with brain maturation, this work underscores the need to consider both grey and white matter when assessing the neurodevelopmental pathways to outcomes across the lifespan.

neuroscience↗

Trajectories of brain organisation transition from predicting externalising to internalising symptoms across adolescence

Understanding the dynamics of brain-behaviour relationships during adolescence is critical for elucidating the neurodevelopmental basis of mental health. Leveraging two large-scale longitudinal cohorts--the Adolescent Brain Cognitive Development (ABCD) and IMAGEN studies, comprising over 10,000 participants aged 10 to 22 years with six waves of multimodal neuroimaging and behavioural data, we applied multi-view sparse canonical correlation analysis to investigate evolving associations between structural MRI, resting-state functional connectivity, and multi-domain behavioural measures. Our findings reveal four fundamental patterns of developmental reorganisation in brain-psychopathology relationships. First, symptom profiles evolved from predominantly externalising features (aggression, attention problems) at ages 10-12 toward global psychopathology by age 14, then transitioned toward internalising features (e.g., anxiety, depression) by ages 19-22, reflecting fundamental shifts in vulnerability from behavioural dysregulation to affective disturbance. Second, cortical thickness exhibited negative associations with externalising symptom profiles throughout development. During early adolescence (ages 10-14) this was driven by broadly distributed decreases across sensorimotor, temporal, visual, and cingulate regions alongside overall mean cortical thickness. After 14, this diffuse pattern shifted towards late maturing association cortices, notably the dorsolateral prefrontal and lateral temporal cortices. Third, this was accompanied by subcortical effects that exhibited greater age-specificity: whilst cerebellar volume contributions were evident at most timepoints, basal ganglia volume influence was principally evident in early development (ages 10-12), with thalamic structures and global subcortical grey matter volume becoming dominant at age 14, marking a transition in which subcortical structures mediate psychopathology associations. Fourth, functional connectivity showed a more dynamic developmental trajectory. During early adolescence, symptom associations were driven by positive connectivity between cognitive control and sensorimotor networks, whereas late adolescence exhibited predominantly positive connectivity patterns, transitioning from dense sensorimotor-frontoparietal configurations to more specific patterns involving the central executive and default-mode networks. These findings fundamentally challenge static biomarker models, demonstrating that adolescent psychopathology reflects developmentally contingent brain-behaviour relationships rather than static neural markers. Age 14 emerges as a critical inflection point marked by convergent thalamic reconfiguration, global subcortical grey matter dominance, and symptom profile transitions. This work provides an empirical foundation for precision mental health strategies tailored to specific developmental windows, with implications for reducing psychiatric burden in youth.

neuroscience↗

Digital Twin Brain simulation and manipulation of a functional brain network underlying mental illness

Linking synaptic-level perturbations to distributed brain-network dynamics remains a central challenge for understanding and treating mental illness. Although recent whole-brain models can reproduce individual brain activity patterns, they largely function as descriptive simulators rather than mechanistic, intervention-capable systems. Here we present an intervention-capable digital twin of the human brain, integrating individual neuroanatomy and task-evoked dynamics within a neuronal-scale framework. Individualised digital twin brains recapitulate a participant-specific compact cortico-subcortical network phenotype that captures transdiagnostic psychopathology across population and clinical cohorts. In silico modulation of excitatory and inhibitory synaptic conductance produces bidirectional, heterogeneous network responses across individuals. Population-scale simulations stratify individuals and predict longitudinal symptom trajectories from DTB-derived response profiles. Independent pharmacological functional MRI data further validate the predicted baseline-dependent network responses in vivo. Together, these findings establish digital brain models as experimental platforms for mechanistic perturbation, behavioural prediction and stratification, providing a foundation for precision neuroscience and psychiatry.

neuroscience↗

Brain structure-function coupling - relationship with language lateralisation

Language is one of the most extensively studied lateralised cognitive functions in the human brain, predominantly relying on the left hemisphere in most individuals. However, the mechanisms by which a stable white matter architecture underpins individual language functions remain unclear. Previous studies have employed structural connectivity (SC) and functional connectivity (FC) coupling for individual fingerprinting and task decoding, suggesting that variability in brain entropy may serve as a distinguishing characteristic for language lateralisation. We examined a large cohort of healthy adults (n = 285) to investigate SC-FC coupling and identify markers distinguishing different language laterality groups. Functional connectivity was measured using resting-state fMRI (rsfMRI) time-series data, while structural connectivity was determined via probabilistic fibre tractography. SC-FC coupling was investigated using the SENSAAS language atlas and defined as the Pearson correlation between non-zero elements of regional structural and functional connectivity profiles. Group differences were assessed using the PALM toolbox in FSL. Our findings revealed that increased SC-FC coupling in the left precentral sulcus was associated with typical language lateralisation, while increased coupling in the right middle temporal gyrus and left anterior insula was observed in individuals with atypical language lateralisation (pFDR < 0.05). Non-lateralised individuals exhibited increased coupling in the left anterior insula compared to lateralised (pFDR<0.05). SC-FC coupling offers a promising framework to uncover functional and anatomical differences among individuals with varying language lateralisation. This regional specificity indicates that typical, atypical, and non-lateralised profiles rely on different structural-functional alignments, likely reflecting the recruitment of alternative pathways for language processing.

neuroscience↗

Language laterality and cognitive skills: does anatomy matter?

Brain anatomy, particularly white matter microstructure, is thought to play a critical role in the relationships between cognitive function and language lateralisation. This study investigates whether white matter microstructural parameters of the arcuate fasciculus and corpus callosum is associated with cognitive performance across distinct language lateralisation groups. Neuroimaging and cognitive data from 279 healthy adults were sourced from the BIL&GIN database. Participants completed a sentence production fMRI task, diffusion MRI, and cognitive tasks assessing verbal, visuospatial, and arithmetic skills. Significant positive associations were observed in strongly atypical individuals between fractional anisotropy in the splenium and working memory (R2 = 0.96, pFDR = 0.042) and between FA in the genu and visuospatial attention (R2 = 0.92, pFDR = 0.042). ANCOVA revealed that cross-dominant individuals had significantly lower visuospatial attention scores compared to consistently lateralised individuals (pFDR = 0.02). These findings challenge the notion that atypical lateralisation is inherently maladaptive and suggest that white matter pathways may serve as an alternative mechanism for supporting cognitive function in individuals with rightward language dominance. Furthermore, the results highlight the cognitive disadvantages of crossed dominance, implicating disrupted interhemispheric communication as a potential underlying mechanism.

neuroscience↗

Brain Diffusion Transformer for Personalized Neuroscience and Psychiatry

Task-fMRI analyses typically focus on localized activation contrasts between stimuli, neglecting the brains dynamic hierarchy. We introduce Brain Diffusion Transformer (Brain-DiT), a deep generative model capturing recurrent processing underlying individualized neurocognitive state transitions via functional networks. Without prior assumptions, Brain-DiT identifies canonical cognitive regions in the brain and reveals replicable subgroups with distinct neural circuits in large cohorts, offering critical clinical insights overlooked by traditional methods: individuals exhibiting negative emotion bias, linked to language-related regions, had a 12-fold higher likelihood of major depression, and those with maladaptive inhibition strategies, associated with overactive medial frontal regions, showed a 9-fold increased risk of alcohol abuse. By bridging cognitive theory and psychiatric applications, Brain-DiT provides a unified analytical paradigm, paving the way for operational personalized medicine in psychiatry.

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Benchmarking Stroke Outcome Prediction through Comprehensive Data Analysis - NeuralCup 2023

Stroke remains a leading cause of mortality and long-term disability worldwide, with variable recovery trajectories posing substantial challenges in anticipating post-event care and rehabilitation planning. To address these challenges, we established the NeuralCup consortium to benchmark predictive models of stroke outcome through a collaborative, data-driven approach. This study presents findings from 15 international teams who used a comprehensive dataset including clinical and imaging data, to identify and compare predictors of motor, cognitive, and emotional outcomes one year post-stroke. Our analyses integrated traditional statistical approaches and novel machine learning algorithms to uncover optimal recipes for predicting each domain. The differences in these optimal recipes reflect distinct brain mechanisms in response to different tasks. Key predictors across all domains included infarct characteristics, T1-weighted MRI sequences, and demographic factors. Additionally, integrating FLAIR imaging and white matter tract analysis significantly improved the prediction of cognitive and motor outcomes, respectively. These findings support a multifaceted approach to stroke outcome prediction, underscoring the potential of collaborative data science to develop personalized care strategies that enhance recovery and quality of life for stroke survivors. To encourage further model development and validation, we provide access to the training dataset at http://neuralcup.bcblab.com

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Genetic-Dependent Brain Signatures of Resilience: Interactions among Childhood Abuse, Genetic Risks and Brain Function

Resilience to emotional disorders is critical for adolescent mental health, especially following childhood abuse. Yet, brain signatures of resilience remain undetermined due to the differential susceptibility of the brains emotion processing system to environmental stresses. Analyzing brains responses to angry faces in a longitudinally large-scale adolescent cohort (IMAGEN), we identified two functional networks related to the orbitofrontal and occipital regions as candidate brain signatures of resilience. In girls, but not boys, higher activation in the orbitofrontal-related network was associated with fewer emotional symptoms following childhood abuse, but only when the polygenic burden for depression was high. This finding defined a genetic-dependent brain (GDB) signature of resilience. Notably, this GDB signature predicted subsequent emotional disorders in late adolescence, extending into early adulthood and generalizable to another independent prospective cohort (ABCD). Our findings underscore the genetic modulation of resilience-brain connections, laying the foundation for enhancing adolescent mental health through resilience promotion.

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Bullying and Early Brain Development: A Longitudinal Structural Magnetic Resonance Imaging Study from Adolescence to Early Adulthood

This study investigated associations between bullying victimization and brain development using longitudinal structural MRI data from the IMAGEN cohort (n = 2,094; 1,009 females) across three time points ([~]14, [~]19, and [~]22 years). A data-driven analysis revealed that higher bullying victimization was significantly associated with accelerated volumetric growth in subcortical and limbic regions, including the putamen ({beta} = 0.12, 95% CI: 0.10-0.15), amygdala ({beta} = 0.07, 95% CI: 0.05-0.09), hippocampus ({beta} = 0.06, 95% CI: 0.04- 0.08), and anterior cingulate cortex (caudal: {beta} = 0.05, 95% CI: 0.03-0.07; rostral: {beta} = 0.06, 95% CI: 0.04-0.08). In contrast, bullying victimization was also significantly associated with reduced volumetric growth in the cerebellum ({beta} = -0.09, 95% CI: -0.11 to -0.07), entorhinal cortex ({beta} = -0.10, 95% CI: -0.13 to -0.07), and insula ({beta} = -0.08, 95% CI: -0.11 to -0.06).Exploratory analyses indicated that females exhibited more pronounced changes in emotional processing regions, while males showed greater changes in motor and sensory areas. Overall, the findings indicate that bullying victimization is associated with widespread structural differences in brain development from adolescence to early adulthood, with sex-specific trajectories.

neuroscience↗

Anatomical connectivity profile development constrains medial-lateral topography in the dorsal prefrontal cortex

The prefrontal cortex (PFC) is a highly variable, evolutionarily expanded brain region that is engaged in multiple cognitive processes. The subregions of the PFC mature relatively late compared with other brain regions, and the maturation times vary between these subregions. Among these, the dorsomedial and dorsolateral prefrontal cortex (dmPFC and dlPFC) share a parallel topographic pattern of functional connectivity, while participating in different types of complex behaviors. However, the developmental trajectories of the two areas remain obscure. In this study, we uncovered differences in the developmental trends of the dmPFC and dlPFC. These differences were mainly caused by structural and functional changes in the medial area of the superior frontal gyrus (SFG). The developmentally different arealization patterns were verified using multiple parcellation approaches with multimodal data, including structural magnetic resonance imaging (sMRI), diffusion MRI (dMRI), resting state functional MRI (rfMRI), and a publicly available transcriptomic dataset. Human brain gene expression data was also used to perform downstream analyses, which could inform us about the potential biological mechanisms underlying the developmentally different arealizations. Furthermore, behavioral analyses hinted at the effects of regionalization on ontogeny. In brief, this study revealed a tendency toward a medial-lateral prefrontal division and can provide a fuller understanding of the potential underlying genetic underpinnings as well as of the potential effects on developmental behavior.

neuroscience↗

The genetic architecture of language functional connectivity

Language is a unique trait of the human species, of which the genetic architecture remains largely unknown. Through language disorders studies, many candidate genes were identified. However, such complex and multifactorial trait is unlikely to be driven by only few genes and case-control studies, suffering from a lack of power, struggle to uncover significant variants. In parallel, neuroimaging has significantly contributed to the understanding of structural and functional aspects of language in the human brain and the recent availability of large scale cohorts like UK Biobank have made possible to study language via image-derived endophenotypes in the general population. Because of its strong relationship with task-based fMRI activations and its easiness of acquisition, resting-state functional MRI have been more popularised, making it a good surrogate of functional neuronal processes. Taking advantage of such a synergistic system by aggregating effects across spatially distributed traits, we performed a multivariate genome-wide association study (mvGWAS) between genetic variations and resting-state functional connectivity (FC) of classical brain language areas in the inferior frontal (pars opercularis, triangularis and orbitalis), temporal and inferior parietal lobes (angular and supramarginal gyri), in 32,186 participants from UK Biobank. Twenty genomic loci were found associated with language FCs, out of which three were replicated in an independent replication sample. A locus in 3p11.1, regulating EPHA3 gene expression, is found associated with FCs of the semantic component of the language network, while a locus in 15q14, regulating THBS1 gene expression is found associated with FCs of the perceptualmotor language processing, bringing novel insights into the neurobiology of language.

genetics↗

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.

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Adolescent to young adult longitudinal development of subcortical volumes in two European sites with four waves

Adolescent subcortical structural brain development might underlie psychopathological symptoms, which often emerge in adolescence. At the same time, sex differences exist in psychopathology, which might be mirrored in underlying sex differences in structural development. However, previous studies showed inconsistencies in subcortical trajectories and potential sex differences. Therefore, we aimed to investigate the subcortical structural trajectories and their sex differences across adolescence using for the first time a single cohort design, the same quality control procedure, software and a general additive mixed modeling approach. We investigated two large European sites from ages 14 to 24 with 503 participants and 1408 total scans from France and Germany as part of the IMAGEN project including four waves of data acquisition. We found significantly larger volumes in males versus females in both sites and across all seven subcortical regions. Sex differences in age-related trajectories were observed across all regions in both sites. Our findings provide further evidence of sex differences in longitudinal adolescent brain development of subcortical regions and thus might eventually support the relationship of underlying brain development and different adolescent psychopathology in boys and girls.

neuroscience↗

Satellite Imaging of Global Urbanicity relate to Adolescent Brain Development and Behavior

Urbanicity, the impact of living in urban areas, is among the greatest environmental challenges for mental health. While urbanicity might be distinct in different sociocultural conditions and geographic locations, there are likely to exist common features shared in different areas of the globe. Understanding these common and specific relations of urbanicity with human brain and behavior will enable to assess the impact of urbanicity on mental disorders, especially in childhood and adolescence, where prevention and early interventions are likely to be most effective.\n\nWe constructed from satellite-based remote sensing data a factor for urbanicity that was highly correlated with population density ground data. This factor, UrbanSat was utilized in the Chinese CHIMGEN sample (N=831) and the longitudinal European IMAGEN cohort (N=810) to investigate if exposure to urbanicity during childhood and adolescence is associated with differences in brain structure and function in young adults, and if these changes are linked to behavior.\n\nUrbanicity was found negatively correlated with medial prefrontal cortex volume and positively correlated with cerebellar vermis volume in young adults from both China and Europe. We found an increased correlation of urbanicity with functional network connectivity within- and between- brain networks in Chinese compared to European participants. Urbanicity was highly correlated with a measure of perceiving a situation from the perspective of others, as well as symptoms of depression in both datasets. These correlations were mediated by the structural and functional brain changes observed. Susceptibility to urbanicity was greatest in two developmental windows during mid-childhood and adolescence.\n\nUsing innovative technology, we were able to probe the relationship between urban upbringing with brain change and behavior in different sociocultural conditions and geographic locations. Our findings help to identify shared and distinct determinants of adolescent brain development and mental health in different regions of the world, thus contributing to targeted prevention and early-intervention programs for young people in their unique environment. Our approach may be relevant for public health, policy and urban planning globally.

neuroscience↗

Superior temporal sulcus hypoperfusion in children with autism spectrum disorder: an arterial spin-labeling magnetic resonance study

Advances in neuroimaging techniques have significantly improved our understanding of the neural basis of autism spectrum disorder (ASD). Several attempts have been made to label the main neuroimaging phenotype of ASD, mostly by anatomical and functional activation studies, but none of the frameworks have been without controversy. Over the past decade, a renewed interest for rest brain functioning has emerged in the scientific community, reflected on a large number of resting state fMRI (rs-fMRI) studies, but results remain heterogeneous. It is possible today to investigate rest brain functioning by measuring rest cerebral blood flow (CBF) with MRI using arterial spin labeling (ASL). Here, we investigated rest CBF abnormalities using non-invasive ASL-MRI in 18 children with ASD without cognitive delay (10.4 {+/-} 2.8 y) and 30 typically developing children (10.6 {+/-} 3.0 y). Following quality control, images from a final sample of 12 children with ASD (11.2 {+/-} 2.9 y) and 28 typically developing children (10.1 {+/-} 2.5 y) were analyzed. Whole brain voxel-by-voxel analysis showed significant rest CBF decrease in temporal regions, mainly in the superior temporal sulcus (STS), in children with ASD. This hypoperfusion was individually detected in 83% of children with ASD. Finally, negative correlation was observed between ASD severity scores and rest CBF in the right posterior STS. Strikingly, despite the small sample studied here, our results are extremely similar to previous PET and SPECT findings describing decreased rest CBF in the same superior temporal regions at group and individual levels, as well as correlation with symptoms severity. The congruence between these results, with different methods and in different ASD profiles, reinforce the strength of rest functional abnormalities within these superior temporal regions in ASD and strongly indicates it might be a core characteristic of the disorder. Identifying a core dysfunctional region in ASD bears direct implications to the development of novel therapeutic interventions, such as transcranial magnetic stimulation. In addition, if confirmed in a larger sample, rest temporal hypoperfusion could become a reliable brain imaging biomarker in ASD.

neuroscience↗

Rest functional brain maturation during the first year of life

The first year of life is a key period of brain development, characterized by dramatic structural and functional modifications. Here, we measured rest cerebral blood flow (CBF) modifications throughout babies first year of life using arterial spin labeling magnetic resonance imaging sequence in 52 infants, from 3 to 12 months of age. Overall, global rest CBF significantly increased during this age span. In addition, we found marked regional differences in local functional brain maturation. While primary sensorimotor cortices and insula showed early maturation, temporal and prefrontal region presented great rest CBF increase across the first year of life. Moreover, we highlighted a late and remarkably synchronous maturation of the prefrontal and posterior superior temporal cortices. These different patterns of regional cortical rest CBF modifications reflect a timetable of local functional brain maturation and are consistent with babys cognitive development within the first year of life.

neuroscience↗

Sleep, regional grey matter volumes, and psychological functioning in adolescents

Changing sleep rhythms in adolescents often lead to sleep deficits and increased variability in sleep schedules. The adolescent brain, and in particular the rapidly developing structures involved in emotional control, are vulnerable to external and internal factors. In our previous study in adolescents at age 14, we observed a strong relationship between weekend sleep schedules and regional medial prefrontal cortex grey matter volumes. Here, we aimed to assess whether this relationship remained in this group of adolescents of the general population at the age of 16 (n=101; mean age 16.8 years; 55% girls). We further examined grey matter volumes in the hippocampi and the amygdalae, calculated with voxel-based morphometry. In addition, we investigated the relationship between regional grey matter volumes with psychological functioning. Sleep was assessed with self-reports and psychological functioning with the Strengths and Difficulties Questionnaire and tests on working memory and impulsivity. Later weekend wake-up times were associated with smaller grey matter volumes in the medial prefrontal cortex and the amygdalae, and greater weekend delays in wake-up time were associated with smaller grey matter volumes in the right hippocampus and amygdala. The medial prefrontal cortex region mediated the correlation between weekend wake up time and both externalising and internalising symptoms. Paying attention to regular sleep habits during adolescence could act as a protective factor against the emergence of psychopathology via enabling favourable brain development.

neuroscience↗

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.

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