Biology subjects

IMAGEN Consortium,

Publications and source records attributed to IMAGEN Consortium,.

9 recordsLinked to original sources

bioRxiv2026

Early life stress alters lifespan trajectories of amygdala development: a cross-species model of amygdala burnout

Early-life stress is associated with alterations in amygdala volume, but findings vary across studies and species. Rodent models typically report increased amygdala volume, whereas human studies often find reductions or mixed effects. We propose the amygdala burnout hypothesis, which suggests that early-life stress alters amygdala developmental trajectories, producing initial volumetric increases that are followed by reductions later in life. To test this hypothesis, we examined amygdala development across rodent and human cohorts spanning adolescence to older adulthood. In rodents, chronic stress was associated with increased amygdala nuclei volumes during adolescence. Comparable increases were observed in adolescents from the IMAGEN consortium, with evidence of a dose-dependent association between childhood stress and amygdala developmental trajectories. In contrast, analyses of older adults from the UK Biobank revealed reduced bilateral amygdala volume associated with early-life stress. Together, these findings support a developmental model that reconciles previously conflicting observations across species and age groups. Early-life stress is associated with alterations in amygdala volume, but findings vary across studies and species. Rodent models typically report increased amygdala volume, whereas human studies often find reductions or mixed effects. We propose the amygdala burnout hypothesis, which suggests that early-life stress alters amygdala developmental trajectories, producing initial volumetric increases that are followed by reductions later in life. To test this hypothesis, we examined amygdala development across rodent and human cohorts spanning adolescence to older adulthood. In rodents, chronic stress was associated with increased amygdala nuclei volumes during adolescence. Comparable increases were observed in adolescents from the IMAGEN consortium, with evidence of a dose-dependent association between childhood stress and amygdala developmental trajectories. In contrast, analyses of older adults from the UK Biobank revealed reduced bilateral amygdala volume associated with early-life stress. Together, these findings support a developmental model that reconciles previously conflicting observations across species and age groups.

neuroscience↗

bioRxiv2026

Sex-specific associations of childhood adversity with frontostriatal network organization and anhedonia in young adulthood

IntroductionAnhedonia is a transdiagnostic psychiatric symptom linked to increased functional connectivity between the prefrontal cortex and striatum. Here, we examined how dimensions of early adversity contribute to this profile of connectivity. MethodsIn a European community sample of young adults (IMAGEN), we examined cross-sectional (n=613) and longitudinal (n=332) associations of adversity dimensions with resting-state fMRI-derived connectivity. We selected 10 ROIs from anhedonia literature, defined in the functional images as 4mm-radius spheres. We then used network-based regression models to identify clusters of ROI-ROI connections associated with threat and deprivation scores, using interaction terms to examine sex and age-specific associations. We also examined associations between adversity and anhedonia, operationalized using factor analysis of six items from self-report surveys. ResultsAt age 18-22, we identified sex-specific associations between deprivation and connectivity for a cluster of 9 ROI-ROI connections (p-FWE=0.038), primarily involving the nucleus accumbens. Specifically, we observed positive associations between deprivation and connectivity in males, and negative associations in females. In the longitudinal analysis, negative deprivation associations in females attenuated with age for a cluster of 14 connections (p-FWE=0.009). A cluster of 17 connections also had initial positive associations with threat in females that attenuated with age (p-FWE=0.008). No such longitudinal changes were observed in males. Higher deprivation was linked to increased later anhedonia in males but not females (p=0.026). ConclusionCompared to females, young adult males may be more vulnerable to developing anhedonia after experiencing deprivation in childhood. Dimensions of early adversity are linked to distinct pathways of frontostriatal development.

neuroscience↗

bioRxiv2026

Protracted Maturation of Proactive and Reactive Systems Predicts Cognitive Stability and Psychopathology : A longitudinal multi-cohort study

Inhibitory control matures progressively from childhood to early adulthood, yet the neural mechanisms driving this development and their relevance to psychiatric risk remain poorly understood. Guided by the Dual Cognitive Control model, we leveraged longitudinal fMRI from two independent cohorts in the US (ABCD, ages 9-12) and Europe (IMAGEN, ages 14-22) to map the spatiotemporal dynamics of reactive and proactive control using novel single-trial modeling and representational similarity analysis. We found both reactive and proactive stopping networks stabilize after mid-adolescence, tracking the developmental patterns of inhibitory control and behavioral stability. By decoding trial-by-trial fluctuations along a speed-caution continuum, we demonstrate that brain-behavior coupling to a proactive "Safe state" tightens progressively with age. Furthermore, network-level representational coherence of this Safe state emerged as a scanner-invariant, trait-like biomarker that robustly predicted inhibitory control, behavioral stability, and transdiagnostic psychopathology across multiple developmental windows, providing a validated neural phenotype for precision psychiatry.

neuroscience↗

bioRxiv2025

Chronic pain is linked to a resting-state neural archetype that optimizes learning from punishments

Chronic pain is a leading cause of disability, yet its underlying susceptibility traits remain unclear. Disorders like chronic pain may stem from extreme neural types, or archetypes, optimized for specific cognitive strategies and reflected in patterns of resting-state networks. Here, we examined a sample from the general population (n = 892) and three clinical samples with subacute back pain (n = 76), chronic back pain (n = 30), and treatment-resistant depression (n = 24). Using the sample from the general population, we found three neural archetypes that prioritize different cognitive strategies. Clinical pain samples, compared to the sample from the general population, mapped close to an archetype optimized for punishment learning (Archetype P). We replicated these results by recomputing the archetypes starting from the clinical pain samples, additionally revealing an association between Archetype P and pain severity. These findings suggest a neural-cognitive trait underlying susceptibility to chronic pain.

neuroscience↗

bioRxiv2024

Adolescent maturation of cortical excitation-inhibition balance based on individualized biophysical network modeling

The balance of excitation and inhibition is a key functional property of cortical microcircuits which changes through the lifespan. Adolescence is considered a crucial period for the maturation of excitation-inhibition balance. This has been primarily observed in animal studies, yet human in vivo evidence on adolescent maturation of the excitation-inhibition balance at the individual level is limited. Here, we developed an individualized in vivo marker of regional excitation-inhibition balance in human adolescents, estimated using large-scale simulations of biophysical network models fitted to resting-state functional magnetic resonance imaging data from two independent cross-sectional (N = 752) and longitudinal (N = 149) cohorts. We found a widespread relative increase of inhibition in association cortices paralleled by a relative age-related increase of excitation, or lack of change, in sensorimotor areas across both datasets. This developmental pattern co-aligned with multiscale markers of sensorimotor-association differentiation. The spatial pattern of excitation-inhibition development in adolescence was robust to inter-individual variability of structural connectomes and modeling configurations. Notably, we found that alternative simulation-based markers of excitation-inhibition balance show a variable sensitivity to maturational change. Taken together, our study highlights an increase of inhibition during adolescence in association areas using cross sectional and longitudinal data, and provides a robust computational framework to estimate microcircuit maturation in vivo at the individual level.

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bioRxiv2023

Human cortex development is shaped by molecular and cellular brain systems

Human brain morphology undergoes complex changes over the lifespan. Despite recent progress in tracking brain development via normative models, current knowledge of underlying biological mechanisms is highly limited. We demonstrate that human cortical thickness development and aging trajectories unfold along patterns of molecular and cellular brain organization, traceable from population-level to individual developmental trajectories. During childhood and adolescence, cortex-wide spatial distributions of dopaminergic receptors, inhibitory neurons, glial cell populations, and brain-metabolic features explain up to 50% of variance associated with a lifespan model of regional cortical thickness trajectories. In contrast, modeled cortical thickness change patterns during adulthood are best explained by cholinergic and glutamatergic neurotransmitter receptor and transporter distributions. These relationships are supported by developmental gene expression trajectories and translate to individual longitudinal data from over 8,000 adolescents, explaining up to 59% of developmental change at cohort- and 18% at single-subject level. Integrating neurobiological brain atlases with normative modeling and population neuroimaging provides a biologically meaningful path to understand brain development and aging in living humans.

neuroscience↗

bioRxiv2021

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↗

bioRxiv2019

Neurobehavioural characterisation and stratification of reinforcement-related behaviour

AbstractReinforcement-related cognitive processes, such as reward processing, impulsiveness and emotional processing are critical components of externalising and internalising behaviours. It is unclear to what extent each of these processes contributes to individual behavioural symptoms, how their neural substrates give rise to distinct behavioural outcomes, and if neural profiles across different reinforcement-related processes might differentiate individual behaviours. We created a statistical framework that enabled us to directly compare functional brain activation during reward anticipation, motor inhibition and viewing of emotional faces in the European IMAGEN cohort of 2000 14-year-old adolescents. We observe significant correlations and modulation of reward anticipation and motor inhibition networks in hyperactivity, impulsivity, inattention and conduct symptoms, and describe neural signatures across neuroimaging tasks that differentiate these behaviours. We thus characterise shared and distinct functional brain activation patterns that underlie different externalising symptoms and identify neural stratification markers, while accounting for clinically observed co-morbidity.

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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.

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