publications
Electronic versions of papers are provided as a professional courtesy to ensure timely dissemination of academic work for individual, noncommercial purposes. Copyright resides with the respective copyright holders, as stated within each paper. These files may not be reposted without permission.
2025
- Imaging NeuroscienceWhen age tips the balance: A dual mechanism affecting hemispheric specialization for languageImaging Neuroscience, 2025
Aging is accompanied by changes in brain architecture that alter the lateralization of functional networks. In this study, we examined how hemispheric specialization changes across the adult lifespan by analyzing resting-state fMRI and structural MRI data from 728 typical adults aged 18 to 88 years. Using the Language-and-Memory Network atlas, we quantified regional asymmetries in functional connectivity along the cortex’s principal gradient, and normalized regional volumes across 37 bilateral regions. We identified two distinct age-related asymmetry trajectories: one pattern revealed a bilateralization of language-dominant regions, while the other showed increasing leftward specialization in multimodal regions associated with memory and language. These opposing patterns emerged around midlife and were linked to performance in language production tasks. By integrating connectivity gradients, structural asymmetries, and behavioral data, our findings provide new evidence for a dual mechanism reshaping functional brain lateralization with age and demonstrate the utility of resting-state metrics in tracking these shifts.
- Sci. DataThe Transdiagnostic Connectome Project: an open dataset for studying brain-behavior relationships in psychiatrySidhant Chopra, Carrisa V. Cocuzza , Connor Lawhead , Jocelyn A. Ricard , Loic Labache, Lauren M. Patrick , Poornima Kumar , Arielle Rubenstein , Julia Moses , Lia Chen , Crystal Blankenbaker , Bryce Gillis , Laura T. Germine , Ilan Harpaz-Rote , BT Thomas Yeo, Justin T. Baker , and Avram J. HolmesScientific Data, 2025
An important aim in psychiatry is to establish valid and reliable associations linking profiles of brain functioning to clinically relevant symptoms and behaviors across patient populations. To advance progress in this area, we introduce an open dataset containing behavioral and neuroimaging data from 241 individuals aged 18 to 70, comprising 148 individuals meeting diagnostic criteria for a broad range of psychiatric illnesses and a healthy comparison group of 93 individuals. These data include high-resolution anatomical scans, multiple resting-state, and task-based functional MRI runs. Additionally, participants completed over 50 psychological and cognitive assessments. Here, we detail available behavioral data as well as raw and processed MRI derivatives. Associations between data processing and quality metrics, such as head motion, are reported. Processed data exhibit classic task activation effects and canonical functional network organization. Overall, we provide a comprehensive and analysis-ready transdiagnostic dataset to accelerate the identification of illness-relevant features of brain functioning, enabling future discoveries in basic and clinical neuroscience.
- Clin. Psychol. Sci.Longitudinal Clustering of Psychopathology Across Childhood and Adolescence: An Approach Toward Developmentally Based ClassificationConnor Lawhead , Jamilah Silver , Thomas Olino , Loic Labache, Swanie Juhng , H Andrew Schwart , and Daniel KleinClinical Psychological Science, 2025
Current classification systems of psychopathology focus on cross-sectional symptoms rather than continuity, discontinuity, and comorbidity across development. Here, a community sample of 600 youths was assessed every 3 years from early childhood through late adolescence using semistructured diagnostic interviews. We used longitudinal k-means clustering of joint-diagnostic trajectories to identify six distinct clusters (healthy, childhood anxiety, childhood/adolescent attention-deficit/hyperactivity disorder, adolescent depression/anxiety, adolescent depression/substance use, and early childhood disruptive behavior). Comparing psychopathology clusters with the healthy cluster on age-3 predictors (parental education and psychopathology, early environment, temperament, cognitive and social functioning) and age-18 functional outcomes, we found that the clusters captured developmental patterning of psychopathology not apparent in cross-sectional nosology. The study serves as a proof of principle in applying a longitudinal clustering approach to common mental disorders, affording a rich perspective on the unfolding of sequential comorbidity and heterotypic continuity and identifying transdiagnostic subgroups with meaningful clinical, family, and temperamental correlates.
- bioRxivBrain network dynamics reflect psychiatric illness status and transdiagnostic symptom profiles across health and diseaseCarrisa V Cocuzza , Sidhant Chopra, Ashlea Segal , Loic Labache, Rowena Chin , Kaley Joss , and Avram J HolmesbioRxiv, 2025
The network organization of the human brain dynamically reconfigures in response to changing environmental demands, an adaptive process that may be disrupted in a symptom-relevant manner across psychiatric illnesses. Here, in a transdiagnostic sample of participants with (n=134) and without (n=85) psychiatric diagnoses, functional connectomes from intrinsic (resting-state) and task-evoked fMRI were decomposed to identify constraints on brain network dynamics across six cognitive states. Hierarchical clustering of 110 clinical, behavioral, and cognitive measures identified participant-specific symptom profiles, revealing four core dimensions of functioning: internalizing, externalizing, cognitive, and social/reward. Brain network dynamics were flattened across cognitive states in individuals with psychiatric illness and could be used to accurately separate dimensional symptom profiles more robustly than both case-control status and primary diagnostic grouping. A key role of inhibitory cognitive control and frontoparietal network interactions was uncovered through systematic model comparison. We provide novel evidence that brain network dynamics can accurately differentiate the extent that psychiatrically-relevant dimensions of functioning are exhibited across health and disease.
- bioRxivThe molecular and cellular underpinnings of human brain lateralizationLoic Labache, Sidhant Chopra, Xi-Han Zhang , and Avram J HolmesbioRxiv, 2025
Hemispheric specialization is a fundamental characteristic of human brain organization, where most individuals exhibit left-hemisphere dominance for language and right-hemisphere dominance for visuospatial attention. While some lateralized functions are evident in other species, the human brain displays a strong, species-wide bias. Despite the evolutionary and functional significance of these asymmetries, their molecular and cellular foundations remain poorly understood. Here, we identify key neurochemical and cellular asymmetries that underpin cortical lateralization. Specifically, we demonstrate lateralized gradients in neurotransmitter receptor densities, particularly along the multimodal monoaminergic-cholinergic axis, as well as asymmetries in mitochondrial distribution and the spatial prevalence of microglia and glutamatergic excitatory neurons. Using a multimodal approach that integrates in vivo functional MRI, PET imaging, and post-mortem transcriptomic and cellular data, we delineate two distinct cortical clusters: a left-lateralized network centered on language processing and a right-lateralized network supporting visuospatial attention. These results highlight a biologically embedded substrate for lateralized cognition that may inform both evolutionary theory and our mechanistic understanding of neuropsychiatric illnesses characterized by disrupted lateralization.
- bioRxivIndependent Lateralization of Language, Attention, and Numerical Cognition Across Task and RestLoic Labache, Isabelle Hesling, and Laure ZagobioRxiv, 2025
Hemispheric functional complementarity is a core organizational principle of the human brain, yet the extent to which lateralization in one domain constrains that of others remains unclear. Two main accounts have been proposed: the causal hypothesis, in which dominance for one function drives complementary dominance in another, and the statistical hypothesis, in which each function lateralizes independently. Using multimodal fMRI in 287 participants from the BIL&GIN cohort, we examined whether language lateralization phenotypes, defined as typical (left-dominant) or atypical (right-dominant), predict hemispheric asymmetries in visuospatial attention and numerical cognition. Task-based activation was measured during line bisection, mental calculation, and numerical interval comparison, and analyzed within domain-specific, functionally defined network atlases. Resting-state functional connectivity metrics were also assessed in the same networks. Across both attention and numerical domains, typical individuals for language showed stronger asymmetries, whereas atypical individuals exhibited weaker, more bilateral patterns. Critically, atypical participants did not show mirror-reversed asymmetries, and language phenotype did not influence intrinsic connectivity metrics in non-language networks. These findings challenge the notion that atypical lateralization represents an inversion of the canonical template and argue against a universal reciprocal link between language dominance and other cognitive domains. Instead, our results support a domain-specific model in which lateralization profiles are shaped by distinct developmental and functional constraints, highlighting the need for multimodal, multi-domain approaches to brain asymmetry.
2024
- Nat. NeurosciVentral attention network connectivity is linked to cortical maturation and cognitive ability in childhoodHao-Ming Dong, Xi-Han Zhang , Loic Labache, Shaoshi Zhang , Leon Qi Rong Ooi , BT Thomas Yeo, Avram J Holmes, Daniel S Margulies , and Xi-Nian ZuoNature Neuroscience, 2024
The human brain experiences functional changes through childhood and adolescence, shifting from an organizational framework anchored within sensorimotor and visual regions into one that is balanced through interactions with later-maturing aspects of association cortex. Here, we link this profile of functional reorganization to the development of ventral attention network connectivity across independent datasets. We demonstrate that maturational changes in cortical organization link preferentially to within-network connectivity and heightened degree centrality in the ventral attention network, whereas connectivity within network-linked vertices predicts cognitive ability. This connectivity is associated closely with maturational refinement of cortical organization. Children with low ventral attention network connectivity exhibit adolescent-like topographical profiles, suggesting that attentional systems may be relevant in understanding how brain functions are refined across development. These data suggest a role for attention networks in supporting age-dependent shifts in cortical organization and cognition across childhood and adolescence.
- Commun. BiolA shared spatial topography links the functional connectome correlates of cocaine use disorder and dopamine D2/3 receptor densitiesJocelyn A Ricard , Loic Labache, Ashlea Segal , Elvisha Dhamala , Carrisa V Cocuzza , Grant Jones , Sarah W Yip , Sidhant Chopra, and Avram J HolmesCommunications Biology, 2024
The biological mechanisms that contribute to cocaine and other substance use disorders involve an array of cortical and subcortical systems. Prior work on the development and maintenance of substance use has largely focused on cortico-striatal circuits, with relatively less attention on alterations within and across large-scale functional brain networks, and associated aspects of the dopamine system. Here, we characterize patterns of functional connectivity in cocaine use disorder and their spatial association with neurotransmitter receptor densities and transporter bindings assessed through PET. Profiles of functional connectivity in cocaine use disorder reliably linked with spatial densities of dopamine D2/3 receptors across independent datasets. These findings demonstrate that the topography of dopamine receptor densities may underlie patterns of functional connectivity in cocaine use disorder, as assessed through fMRI.
- Imaging NeuroscienceAtlas for the Lateralized Visuospatial Attention Networks (ALANs): Insights from fMRI and Network AnalysesImaging Neuroscience, 2024
Hemispheric specialization is central to human evolution and fundamental to human cognitive abilities. While being a defining feature of functional brain architecture, hemispheric specialization is overlooked to derive brain parcellations. Alongside language, which is typically lateralized in the left hemisphere, visuospatial attention is set to be its counterpart in the opposite hemisphere. However, it remains uncertain to what extent the anatomical and functional underpinnings of lateralized visuospatial attention mirror those supporting language. Building on our previous work, which established a lateralized brain atlas for language, we propose a comprehensive cerebral lateralized atlas delineating the anatomo-functional bases of visuospatial attention, Atlas for Lateralized visuospatial Attentional Networks (ALANs). Combining task and resting-state functional connectivity analyses, we identified 95 lateralized brain areas comprising three networks supporting visual (visu), motor (somato-motor), and spatial processing (posterior-medial) processes at work during a line judgment bisection task, and two large-scale networks related to integrated visuospatial attention processes, the parieto-frontal and temporo-frontal networks. We identify hubs playing a pivotal role in the intra-hemispheric interaction within visuospatial attentional networks. The rightward lateralized parieto-frontal encompasses one hub, the inferior frontal sulcus, while the temporo-frontal network encompasses two right hubs: the inferior frontal cortex (pars triangularis and the anterior insula) and the posterior part of the superior temporal sulcus. Compared with our language lateralized atlas, we demonstrated that specific regions within these networks encompass the homotope of the language network from the left hemisphere. This atlas of visuospatial attention provides valuable insights for future investigations into the variability of visuospatial attention and hemispheric specialization research. Additionally, it facilitates more effective comparisons among different studies, thereby enhancing the robustness and reliability of research in the field of attention.
- bioRxivShared and unique lifetime stressor characteristics and brain networks predict adolescent anxiety and depressionYueyue Qu , Sidhant Chopra, Shijie Qu , Carrisa Veronica Cocuzza , Loic Labache, Clemens CC Bauer , Francesca Morfini , Susan Whitfield-Gabrieli , George M Slavich , Jutta Joormann , and othersbioRxiv, 2024
Exposure to major life stressors and aberrant brain functioning have been linked to anxiety and depression, especially during periods of heighted functional brain plasticity, such as adolescence. However, it remains unclear if specific characteristics of major life stressors and functional network disruptions differentially predict anxiety and depression symptoms over time and, if so, whether they act independently or jointly. | Methods: We collected baseline lifetime stressor exposure data and resting-state functional magnetic resonance imaging data in a longitudinal sample of 107 adolescents enriched for anxiety and depressive disorders. We examined five stressor characteristics: physical danger, interpersonal loss, humiliation, entrapment, and role change/disruption. Anxiety and depression symptoms were assessed at baseline, 6-month and 12-month follow-ups. Linear mixed effect models tested if these stressor characteristics, functional connectivity within and between frontoparietal, default, and ventral attention networks, and their interactions differentially predicted anxiety and depression symptoms at 6-month and 12-month follow-ups. | Results: Greater lifetime severity of physical danger and humiliation prospectively predicted increased anxiety symptoms at both follow-ups, whereas greater lifetime entrapment severity prospectively predicted higher anxiety and depression symptoms. Only the effects of lifetime entrapment severity were robust to including within- and between-network functional connectivity metrics and other significantly predictive stressor characteristics. Lifetime entrapment severity more strongly predicted anxiety symptoms in youth with higher default network connectivity. Greater functional connectivity between frontoparietal and default networks prospectively predicted increased depression symptoms. | Conclusions: Taken together, these results underscore the critical importance of using stressor characteristics and functional connectivity jointly to study predictors for adolescent anxiety and depression.
2023
- Aperture NeuroA Practical Guide for Generating Reproducible and Programmatic Neuroimaging VisualizationsSidhant Chopra, Loic Labache, Elvisha Dhamala , Edwina R Orchard , and Avram J HolmesAperture Neuro, 2023
Neuroimaging visualizations form the centerpiece of the interpretation and communication of scientific results, and are a cornerstone for data quality control. Often, these images and figures are produced by manually changing settings on Graphical User Interfaces (GUIs). There now exist many well-documented code-based brain visualization tools that allow users to use code to programmatically generate publication-ready figures directly within programming environments such as R, Python and MATLAB. Here, we provide a rationale for the wide-spread adoption of code-generated brain visualizations by highlighting corresponding advantages in replicability, flexibility, and integration over GUI based tools. We then provide a practical guide outlining the steps required to generate these code-based brain visualizations. We also present a comprehensive table of tools currently available for programmatic brain visualizations and provide examples of visualizations and associated code as a point of reference (https://sidchop.shinyapps.io/braincode_selector/). Finally, we provide a web-app that generates simple code-templates as starting points for these visualizations (https://sidchop.shinyapps.io/braincode/).
- Nat. CommunLanguage network lateralization is reflected throughout the macroscale functional organization of cortexNature Communications, 2023
Hemispheric specialization is a fundamental feature of human brain organization. However, it is not yet clear to what extent the lateralization of specific cognitive processes may be evident throughout the broad functional architecture of cortex. While the majority of people exhibit left-hemispheric language dominance, a substantial minority of the population shows reverse lateralization. Using twin and family data from the Human Connectome Project, we provide evidence that atypical language dominance is associated with global shifts in cortical organization. Individuals with atypical language organization exhibit corresponding hemispheric differences in the macroscale functional gradients that situate discrete large-scale networks along a continuous spectrum, extending from unimodal through association territories. Analyses reveal that both language lateralization and gradient asymmetries are, in part, driven by genetic factors. These findings pave the way for a deeper understanding of the origins and relationships linking population-level variability in hemispheric specialization and global properties of cortical organization.
2022
- Brain Struct. Funct.Stroke disconnectome decodes reading networksStephanie J Forkel, Loic Labache, Parashkev Nachev , Michel Schotten , and Isabelle HeslingBrain Structure and Function, 2022
Cognitive functional neuroimaging has been around for over 30 years and has shed light on the brain areas relevant for reading. However, new methodological developments enable mapping the interaction between functional imaging and the underlying white matter networks. In this study, we used such a novel method, called the disconnectome, to decode the reading circuitry in the brain. We used the resulting disconnection patterns to predict a typical lesion that would lead to reading deficits after brain damage. Our results suggest that white matter connections critical for reading include fronto-parietal U-shaped fibres and the vertical occipital fasciculus (VOF). The lesion most predictive of a reading deficit would impinge on the left temporal, occipital, and inferior parietal gyri. This novel framework can systematically be applied to bridge the gap between the neuropathology of language and cognitive neuroscience.
2021
- Cereb. CortexAtlas55+: brain functional atlas of resting-state networks for late adulthoodGaelle E Doucet, Loic Labache, Paul M Thompson , Marc Joliot, Sophia Frangou , and Alzheimer’s Disease Neuroimaging InitiativeCerebral Cortex, 2021
Currently, several human brain functional atlases are used to define the spatial constituents of the resting-state networks (RSNs). However, the only brain atlases available are derived from samples of young adults. As brain networks are continuously reconfigured throughout life, the lack of brain atlases derived from older populations may influence RSN results in late adulthood. To address this gap, the aim of the study was to construct a reliable brain atlas derived only from older participants. We leveraged resting-state functional magnetic resonance imaging data from three cohorts of healthy older adults (total N = 563; age = 55–95 years) and a younger-adult cohort (N = 128; age = 18–35 years). We identified the major RSNs and their subdivisions across all older-adult cohorts. We demonstrated high spatial reproducibility of these RSNs with an average spatial overlap of 67%. Importantly, the RSNs derived from the older-adult cohorts were spatially different from those derived from the younger-adult cohort (P = 2.3 × 10−3). Lastly, we constructed a novel brain atlas, called Atlas55+, which includes the consensus of the major RSNs and their subdivisions across the older-adult cohorts. Thus, Atlas55+ provides a reliable age-appropriate template for RSNs in late adulthood and is publicly available. Our results confirm the need for age-appropriate functional atlases for studies investigating aging-related brain mechanisms.
- LateralityNeural support of manual preference revealed by BOLD variations during right and left finger-tapping in a sample of 287 healthy adults balanced for handednessLaterality, 2021
We have identified the brain areas involved in Manual Preference (MP) in 143 left-handers (LH) and 144 right-handers (RH). First, we selected the pairs of homotopic regions of interest (hROIs) of the AICHA atlas with significant contralateral activation and asymmetry during the right hand and the left hand Finger-Tapping (FT) both in RH and LH. Thirteen hROIs were selected, including the primary and secondary sensorimotor and premotor cortices, thalamus, dorsal putamen, and cerebellar lobule IV. In both groups, contralateral activations and ipsilateral deactivations were seen, with stronger asymmetries when the preferred hand was used. Comparing with different models for the prediction of MP, we found that the differences in activity during preferred hand minus non-preferred hand movement in 11 contralateral and/or ipsilateral hROIS were best at explaining handedness distribution. Two different mechanisms were identified: 1. Stronger contralateral activity of cortical and cerebellar motor areas during right hand movement, seen in both groups but modulated by handedness; 2. Stronger deactivation in ipsilateral areas during dominant hand movement in both groups, LH here mirroring RH. The present study thus demonstrates that handedness neural support is complex and not simply based on a mirrored organization of hand motor areas.
2020
- eLifeTypical and atypical language brain organization based on intrinsic connectivity and multitask functional asymmetriesLoic Labache, Bernard Mazoyer, Marc Joliot, Fabrice Crivello , Isabelle Hesling, and Nathalie Tzourio-MazoyerElife, 2020
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.
- arXivStudy of inter-individual variability of three-dimensional data table: detection of unstable variables and samplesLoic Labache, Marc Joliot, Gaelle E Doucet, and Jérôme SaraccoarXiv preprint arXiv:2004.05033, 2020
We propose two methodologies in order to better understand the inter-individual variability of resting-state functional Magnetic Resonance Imaging (fMRI) brain data. The aim of the study was to quantify whether the average dendrogram is representative of the initial population and to identify its possible sources of instability. The average dendrogram is based on the Pearson correlation between resting-state networks. The first method identifies networks that can lead to unstable partitions of the average dendrogram. The second method identified homogeneous sub-samples of participants for whom their associated average dendrograms were more stable than that of the whole sample. The two suggested methods have shown significant quantifiable behavioral data results with regards to detecting an unstable network or presence of subpopulations when the noise level does not conceal the structure of the data. These two methods have been successfully applied to establish a cerebral atlas for late adulthood. The first method made it clear that there was no unstable network among the atlas networks. The second method highlighted the presence of two distinct sub-populations with different age-related brain organizations.
2019
- Brain Struct. Funct.A SENtence Supramodal Areas AtlaS (SENSAAS) based on multiple task-induced activation mapping and graph analysis of intrinsic connectivity in 144 healthy right-handersLoic Labache, Marc Joliot, Jérôme Saracco , Gaël Jobard , Isabelle Hesling, Laure Zago, Emmanuel Mellet , Laurent Petit, Fabrice Crivello , Bernard Mazoyer, and othersBrain Structure and Function, 2019
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 three 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 (DC), 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.
- Brain Struct. Funct.Large-scale plurimodal networks common to listening to, producing and reading word lists: an fMRI study combining task-induced activation and intrinsic connectivity in 144 right-handersBrain Structure and Function, 2019
We aimed at identifying plurimodal large-scale networks for producing, listening to and reading word lists based on the combined analyses of task-induced activation and resting-state intrinsic connectivity in 144 healthy right-handers. In the first step, we identified the regions in each hemisphere showing joint activation and joint asymmetry during the three tasks. In the left hemisphere, 14 homotopic regions of interest (hROIs) located in the left Rolandic sulcus, precentral gyrus, cingulate gyrus, cuneus and inferior supramarginal gyrus (SMG) met this criterion, and 7 hROIs located in the right hemisphere were located in the preSMA, medial superior frontal gyrus, precuneus and superior temporal sulcus (STS). In a second step, we calculated the BOLD temporal correlations across these 21 hROIs at rest and conducted a hierarchical clustering analysis to unravel their network organization. Two networks were identified, including the WORD-LIST_CORE network that aggregated 14 motor, premotor and phonemic areas in the left hemisphere plus the right STS that corresponded to the posterior human voice area (pHVA). The present results revealed that word-list processing is based on left articulatory and storage areas supporting the action–perception cycle common not only to production and listening but also to reading. The inclusion of the right pHVA acting as a prosodic integrative area highlights the importance of prosody in the three modalities and reveals an intertwining across hemispheres between prosodic (pHVA) and phonemic (left SMG) processing. These results are consistent with the motor theory of speech postulating that articulatory gestures are the central motor units on which word perception, production, and reading develop and act together.
