Karin Saltoun

Latent brain subtypes of chronotype reveal unique behavioral and health profiles across population cohorts

Julie Carrier

Kai-Florian Storch

Robin I. M. Dunbar

Chronotype is shaped by the complex interplay of endogenous and exogenous factors. This time-enduring trait ties into societal behaviors an… (voir plus)d is linked to psychiatric and metabolic conditions. Despite its multifaceted nature, prior research has treated chronotype as a monolithic trait across the population, risking overlooking substantial heterogeneity in neural and behavioral fingerprints. To uncover hidden subgroups, we develop a supervised pattern-learning framework integrating three complementary brain-imaging modalities with deep behavioral and health profiling from 27,030 UK Biobank participants. We identify five distinct, biologically valid chronotype subtypes. Each demonstrates unique patterns across brain, behavioral and health profiles. External validation in 10,550 US children from the ABCD Study cohort reveals reversed age distributions and replicates sex-associated brain-behavioral patterns, suggesting that potential divergences between chronotype traits observed throughout adulthood may begin to emerge early in life. These findings highlight underappreciated sources of population variation that echo the rhythm of people’s inner clock.

2025-12-21

Nature Communications (publié)

Deep learning reveals that multidimensional social status drives population variation in 11,875 US participant cohort

Avram J. Holmes

Sarah W. Yip

As an increasing realization, many behavioral relationships are interwoven with inherent variations in human populations. Presently, there i… (voir plus)s no clarity in the biomedical community on which sources of population variation are most dominant. The recent advent of population-scale cohorts like the Adolescent Brain Cognitive DevelopmentSM Study (ABCD Study®) are now offering unprecedented depth and width of phenotype profiling that potentially explains interfamily differences. Here, we leveraged a deep learning framework (conditional variational autoencoder) on the totality of the ABCD Study® phenome (8,902 candidate phenotypes in 11,875 participants) to identify and characterize major sources of population stratification. 80% of the top 5 sources of explanatory stratifications were driven by distinct combinations of 202 available socioeconomic status (SES) measures; each in conjunction with a unique set of non-overlapping social and environmental factors. Several sources of variation across this cohort flagged geographies marked by material poverty interlocked with mental health and behavioral correlates. Deprivation emerged in another top stratification in relation to urbanicity and its ties to immigrant and racial and ethnic minoritized groups. Conversely, two other major sources of population variation were both driven by indicators of privilege: one highlighted measures of access to educational opportunity and income tied to healthy home environments and good behavior, the other profiled individuals of European ancestry leading advantaged lifestyles in desirable neighborhoods in terms of location and air quality. Overall, the disclosed social stratifications underscore the importance of treating SES as a multidimensional construct and recognizing its ties into social determinants of health.

2025-08-12

PLOS One (publié)

Deep learning reveals that multidimensional social status drives population variation in 11,875 US participant cohort

Avram J. Holmes

Sarah W. Yip

As an increasing realization, many behavioral relationships are interwoven with inherent variations in human populations. Presently, there i… (voir plus)s no clarity in the biomedical community on which sources of population variation are most dominant. The recent advent of population-scale cohorts like the Adolescent Brain Cognitive DevelopmentSM Study (ABCD Study®) are now offering unprecedented depth and width of phenotype profiling that potentially explains interfamily differences. Here, we leveraged a deep learning framework (conditional variational autoencoder) on the totality of the ABCD Study® phenome (8,902 candidate phenotypes in 11,875 participants) to identify and characterize major sources of population stratification. 80% of the top 5 sources of explanatory stratifications were driven by distinct combinations of 202 available socioeconomic status (SES) measures; each in conjunction with a unique set of non-overlapping social and environmental factors. Several sources of variation across this cohort flagged geographies marked by material poverty interlocked with mental health and behavioral correlates. Deprivation emerged in another top stratification in relation to urbanicity and its ties to immigrant and racial and ethnic minoritized groups. Conversely, two other major sources of population variation were both driven by indicators of privilege: one highlighted measures of access to educational opportunity and income tied to healthy home environments and good behavior, the other profiled individuals of European ancestry leading advantaged lifestyles in desirable neighborhoods in terms of location and air quality. Overall, the disclosed social stratifications underscore the importance of treating SES as a multidimensional construct and recognizing its ties into social determinants of health.

2025-08-12

Public Library of Science ONE (publié)

Latent brain subtypes of chronotype reveal unique behavioral and health profiles: an across-cohort validation

Julie Carrier

Kai-Florian Storch

Robin Dunbar

Chronotype is shaped by the complex interplay of endogenous and exogenous factors. This trait ties into various behaviors in the wider socie… (voir plus)ty and is linked to the prevalence of psychiatric and metabolic conditions. Despite its multifaceted nature, prior research has treated chronotype as a monolithic trait across the population, risking overlooking substantial heterogeneity in neural and behavioral fingerprints of both early risers and night owls. To test for such hidden subgroups, we developed a supervised pattern-learning framework for trait subtyping, integrating three complementary brain-imaging modalities with deep behavior, diagnosis, and drug prescription profiling from 27,030 UK Biobank participants. We identified and characterized five distinct biologically valid chronotype subtypes: (1) typical eveningness, (2) depression-associated eveningness, (3) typical morningness, (4) morningness with greater expression in females, and (5) eveningness with greater expression in males. Each uncovered subtype showed unique patterns across brain, behavioral and health profiles. We finally externally validated these subtypes in 10,550 US children from the ABCD Study® cohort, which revealed reversed age distributions and replicated sex-associated brain-behavioral patterns, underscoring the fact that potential divergences between chronotype traits observed throughout adulthood may begin to emerge early in life. These findings highlight underappreciated sources of population variation that echo the rhythm of people’s inner clock.

2025-07-28

Research Square (prépublication)

Longitudinal changes in brain asymmetry track lifestyle and disease

B. T. Thomas Yeo

Lynn Paul

Jörn Diedrichsen

Human beings may have evolved the largest asymmetries of brain organization in the animal kingdom. Hemispheric left-vs-right specialization … (voir plus)is especially pronounced in species-unique capacities, including emotional processing such as facial judgments, language-based feats such as reading books, and creativity such as musical performances. We hence chart the largest longitudinal brain-imaging resource, and provide evidence that brain asymmetry changes continuously in a manner suggestive of neural plasticity throughout adulthood. In the UK Biobank population cohort, we demonstrate that whole-brain patterns of asymmetry changes show robust phenome-wide associations across 959 distinct variables spanning 11 categories. We also find that changes in brain asymmetry over years co-occur with changes among specific lifestyle markers. We uncover specific brain asymmetry changes which systematically co-occur with entering a new phase of life, namely retirement. Finally, we reveal relevance of evolving brain asymmetry within subjects to major disease categories across ~4500 total medical diagnoses. Our findings speak against the idea that asymmetrical neural systems are conserved throughout adulthood.

2025-06-30

Nature Communications (publié)

Multimodal population study reveals the neurobiological underpinnings of chronotype

Le Zhou

Julie Carrier

Kai-Florian Storch

Robin I. M. Dunbar

2025-04-16

Nature Human Behaviour (inconnu)

Structural covariation between cerebellum and neocortex intrinsic structural covariation links cerebellum subregions to the cerebral cortex

Zilong Wang

Jörn Diedrichsen

Christopher Steele

Sheeba Rani Arnold-Anteraper

B. T. Thomas Yeo

Jeremy D. Schmahmann

Cerebellum’s association with the entire cerebral cortex has not been holistically studied in a unified way. Here, we conjointly character… (voir plus)ize the population-level cortical-cerebellar structural covariation patterns leveraging ∼40,000 UK Biobank participants whole brain structural scans and ∼1,000 phenotypes. We revitalize the previous hypothesis of an anticorrelation between the visual-attention system and advanced associative networks within the cerebellum. We also discovered a novel ipsilateral cerebral-cerebellar associations. Phenome-wide association (PheWAS) revealed real-world implications of the structural covariation patterns.

2024-02-19

bioRxiv (prépublication)

Using rare genetic mutations to revisit structural brain asymmetry

Jakub Kopal

Kuldeep Kumar

Kimia Shafighi

Claudia Modenato

Clara A. Moreau

Guillaume Huguet

Martineau Jean-Louis

Charles-Olivier Martin

Zohra Saci

Nadine Younis

Elise Douard

Khadije Jizi

Alexis Beauchamp-Chatel

Leila Kushan

Ana I. Silva

Marianne B. M. van den Bree

David E. J. Linden

Michael J. Owen … (voir 11 de plus)

Jeremy Hall

Sarah Lippé

Bogdan Draganski

Ida E. Sønderby

Ole A. Andreassen

David C. Glahn

Paul M. Thompson

Carrie E. Bearden

Robert Zatorre

Sébastien Jacquemont

Asymmetry between the left and right brain is a key feature of brain organization. Hemispheric functional specialization underlies some of t… (voir plus)he most advanced human-defining cognitive operations, such as articulated language, perspective taking, or rapid detection of facial cues. Yet, genetic investigations into brain asymmetry have mostly relied on common variant studies, which typically exert small effects on brain phenotypes. Here, we leverage rare genomic deletions and duplications to study how genetic alterations reverberate in human brain and behavior. We quantitatively dissected the impact of eight high-effect-size copy number variations (CNVs) on brain asymmetry in a multi-site cohort of 552 CNV carriers and 290 non-carriers. Isolated multivariate brain asymmetry patterns spotlighted regions typically thought to subserve lateralized functions, including language, hearing, as well as visual, face and word recognition. Planum temporale asymmetry emerged as especially susceptible to deletions and duplications of specific gene sets. Targeted analysis of common variants through genome-wide association study (GWAS) consolidated partly diverging genetic influences on the right versus left planum temporale structure. In conclusion, our gene-brain-behavior mapping highlights the consequences of genetically controlled brain lateralization on human-defining cognitive traits.

2023-04-17

bioRxiv (prépublication)

Rare CNVs and phenome-wide profiling highlight brain structural divergence and phenotypical convergence

Jakub Kopal

Kuldeep Kumar

Claudia Modenato

Clara A. Moreau

Sandra Martin-Brevet

Guillaume Huguet

Martineau Jean-Louis

Charles-Olivier Martin

Zohra Saci

Nadine Younis

Petra Tamer

Elise Douard

Anne M. Maillard

Borja Rodriguez-Herreros

Aurélie Pain

Sonia Richetin

Leila Kushan

Ana I. Silva … (voir 13 de plus)

Marianne B. M. van den Bree

David E. J. Linden

Michael J. Owen

Jeremy Hall

Sarah Lippé

Bogdan Draganski

Ida E. Sønderby

Ole A. Andreassen

David C. Glahn

Paul M. Thompson

Carrie E. Bearden

Sébastien Jacquemont

Copy number variations (CNVs) are rare genomic deletions and duplications that can affect brain and behaviour. Previous reports of CNV pleio… (voir plus)tropy imply that they converge on shared mechanisms at some level of pathway cascades, from genes to large-scale neural circuits to the phenome. However, existing studies have primarily examined single CNV loci in small clinical cohorts. It remains unknown, for example, how distinct CNVs escalate vulnerability for the same developmental and psychiatric disorders. Here we quantitatively dissect the associations between brain organization and behavioural differentiation across 8 key CNVs. In 534 CNV carriers, we explored CNV-specific brain morphology patterns. CNVs were characteristic of disparate morphological changes involving multiple large-scale networks. We extensively annotated these CNV-associated patterns with ~1,000 lifestyle indicators through the UK Biobank resource. The resulting phenotypic profiles largely overlap and have body-wide implications, including the cardiovascular, endocrine, skeletal and nervous systems. Our population-level investigation established brain structural divergences and phenotypical convergences of CNVs, with direct relevance to major brain disorders.

2023-03-01

Nature Human Behaviour (inconnu)

APOE alleles are associated with sex-specific structural differences in brain regions affected in Alzheimer's disease and related dementia

Chloé Savignac

Sylvia Villeneuve

AmanPreet Badhwar

Kimia Shafighi

Chris Zajner

Vaibhav Sharma

Sarah A. Gagliano Taliun

Sali Farhan

Judes Poirier

Alzheimer’s disease is marked by intracellular tau aggregates in the medial temporal lobe (MTL) and extracellular amyloid aggregates in th… (voir plus)e default network (DN). Here, we examined codependent structural variations between the MTL’s most vulnerable structure, the hippocampus (HC), and the DN at subregion resolution in individuals with Alzheimer’s disease and related dementia (ADRD). By leveraging the power of the approximately 40,000 participants of the UK Biobank cohort, we assessed impacts from the protective APOE ɛ2 and the deleterious APOE ɛ4 Alzheimer’s disease alleles on these structural relationships. We demonstrate ɛ2 and ɛ4 genotype effects on the inter-individual expression of HC-DN co-variation structural patterns at the population level. Across these HC-DN signatures, recurrent deviations in the CA1, CA2/3, molecular layer, fornix’s fimbria, and their cortical partners related to ADRD risk. Analyses of the rich phenotypic profiles in the UK Biobank cohort further revealed male-specific HC-DN associations with air pollution and female-specific associations with cardiovascular traits. We also showed that APOE ɛ2/2 interacts preferentially with HC-DN co-variation patterns in estimating social lifestyle in males and physical activity in females. Our structural, genetic, and phenotypic analyses in this large epidemiological cohort reinvigorate the often-neglected interplay between APOE ɛ2 dosage and sex and link APOE alleles to inter-individual brain structural differences indicative of ADRD familial risk.

2022-11-30

PLoS Biology (publié)

Dissociable brain structural asymmetry patterns reveal unique phenome-wide profiles

Ralph Adolphs

Lynn K. Paul

Vaibhav Sharma

Joern Diedrichsen

B. T. Thomas Yeo

2022-11-06

Nature Human Behaviour (inconnu)