Laure Zago

Background: Sex and gender (S/G) differences in cognitive performance are well documented, yet how they relate to brain organization and interact with educational experience during early adulthood, a period of ongoing cognitive maturation, remains unclear. University training exposes young adults to distinct cognitive and social demands, providing a natural context to test whether brain functional connectivity (FC) mediates S/G cognitive differences in an education-dependent manner. Methods: The cohort included students enrolled in declarative fields (formalized, context-independent knowledge, e.g., STEM, law, business administration, philosophy) or situated fields (knowledge embedded in social practice, e.g., psychology, education, medicine). Individual FC networks were derived using the GINNA atlas; edges significantly differing between S/G groups were identified and aggregated into sex-differential nodal FC indices (sdNFIs). Moderated mediation models tested whether academic training fields shape the contribution of these sdNFIs to S/G differences in cognitive performance. Additional exploratory analyses tested whether effects varied across academic stages by including study level as a second moderator. Results: Baseline S/G differences in cognitive performance and sdNFIs were preserved across academic training. Yet sdNFI-mediated pathways linking S/G to cognitive performance varied strongly by knowledge domain. In declarative fields, sdNFIs spanning parietal and medial temporal networks supported male advantages in visuospatial and arithmetic tasks. In situated fields, sdNFIs spanning medial prefrontal and temporo-parietal networks supported female advantages in socio-emotional and verbal tasks. Study-level analyses revealed distinct profiles of sdNFI mediation across tasks. sdNFI-mediated effects were observed primarily at later academic stages (Y2 +) for arithmetic fact retrieval, mental rotation, and emotion recognition, whereas they were present at Y1 but absent at later stages for verbal list learning. Conclusions: These findings demonstrate that academic training selectively shapes FC-cognition relationships in a S/G-specific manner, with declarative and situated knowledge domains recruiting distinct, context-sensitive networks to support performance. By guiding the recruitment of functional networks to meet specific cognitive demands, higher education may constitute a formative period during which the brain architecture supporting S/G cognitive differences is dynamically reorganized. Plain English summary Men and women often differ in certain cognitive skills: women tend to perform better in tasks involving language and recognizing emotions, while men tend to show advantages in spatial reasoning and arithmetic. These differences are well established, but their origins, biological, environmental, or both, remain debated. In this study, we asked whether the type of university education a person follows influences how the brain supports these cognitive differences. We compared students enrolled in fields centered on formal knowledge, such as STEM, law, or philosophy, with students in fields where learning is deeply embedded in human interaction and social practice, such as psychology, education, or medicine. We found that men and women showed similar cognitive differences regardless of their field of study. However, the brain pathways supporting these differences varied depending on the type of training. In formal knowledge fields, brain connections in spatial and memory-related regions supported male advantages in arithmetic and visuospatial tasks. In socially oriented fields, brain connections in regions involved in language and social processing supported female advantages in verbal memory and emotion recognition. Examining these relationships across academic stages revealed different patterns: some brain-performance associations emerged with university training, whereas others faded after the first year, highlighting how flexibly the brain adapts to educational experience. These findings suggest that higher education does not eliminate cognitive differences between men and women, but shapes how these differences are reflected in the brain. Understanding how education interacts with brain development may help design learning environments that better support all students.

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 functional magnetic resonance imaging (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 fractional anisotropy (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 lateralized 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.

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.

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 (R ² = 0.96, pFDR = 0.042) and between FA in the genu and visuospatial attention (R ² = 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.

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.

Since resting-state networks were first observed using magnetic resonance imaging (MRI), their cognitive relevance has been widely suggested. However, to date, the empirical cognitive characterization of these networks has been limited. The present study introduces the Groupe d’Imagerie Neurofonctionnelle Network Atlas, a comprehensive brain atlas featuring 33 resting-state networks. Based on the resting-state data of 1812 participants, the atlas was developed by classifying independent components extracted individually, ensuring consistent between-subject detection. We further explored the cognitive relevance of each GINNA network using Neurosynth-based meta-analytic decoding and generative null hypothesis testing. Significant cognitive terms for each network were then synthesized into appropriate cognitive processes through the consensus of six authors. The GINNA atlas showcases a diverse range of topological profiles, reflecting a broad spectrum of the known human cognitive repertoire. The processes associated with each network are named according to the standard Cognitive Atlas ontology, thus providing opportunities for empirical validation.

Hemispheric asymmetries in white matter tracts are proposed key determinants of language lateralisation, yet evidence in healthy individuals remains inconsistent. This suggests that simple tractography techniques might not be sensitive enough to identify language dominance. Significant insights into the functional organization of the human brain may be achieved by considering networks and brain connectivity, providing more information about discrepancies in people with different hemispheric language dominance. In this study, we examined 285 healthy participants compare their structural connectomes at the whole-brain level and determine the networks responsible for the three different functional language lateralisation groups (typical, atypical and strongly atypical). Probabilistic tractography generated whole-brain tractograms, and white matter fibres were filtered according to anatomical Boolean guidelines. Connectivity matrices with nodes corresponding to supramodal sentence areas in the language atlas and edges weighted by fractional anisotropy (FA) were generated to compare the groups using graph theory and network-based statistic (NBS) approaches. We demonstrated that both atypical (bilateral) and strongly atypical (right-lateralised) lateralisation are characterised by heightened interhemispheric temporal connectivity. Post-hoc analyses showed that strongly atypical individuals exhibited increased temporo-frontal connectivity, while atypical individuals had enhanced temporal and frontal connectivity but lacked temporo-frontal connections. These connectivity patterns diverge from traditional models of hemispheric dominance, suggesting a reliance on integrated bilateral networks in atypically lateralised individuals. This reflects distinct neural mechanisms underlying atypical language organisation, departing from developmental trajectory of typical lateralisation and offering insights into cognitive flexibility and clinical applications.

Since resting-state networks were first observed using magnetic resonance imaging (MRI), their cognitive relevance has been widely suggested. These networks have often been labeled based on their visual resemblance to task activation networks, suggesting possible functional equivalence. However, to date, the empirical cognitive characterization of these networks has been limited. The present study introduces the Groupe d’Imagerie Neurofonctionnelle Network Atlas, a comprehensive brain atlas featuring 33 resting-state networks. Based on the resting-state data of 1812 participants, the atlas was developed by classifying independent components extracted individually, ensuring that the GINNA networks are consistently detected across subjects. We further explored the cognitive relevance of each GINNA network using meta-analytic decoding and generative null hypothesis testing, linking each network with cognitive terms derived from Neurosynth meta-analytic maps. Six independent authors then assigned one or two cognitive processes to each network based on significant terms. The GINNA atlas showcases a diverse range of topological profiles, including cortical, subcortical, and cerebellar gray matter, reflecting a broad spectrum of the known human cognitive repertoire. The processes associated with each network are named according to the standard Cognitive Atlas ontology, informed by two decades of task-related functional magnetic resonance imaging, thus providing opportunities for empirical validation.

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.

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, ALANs. Combining task and resting-state functional connectivity analyses, we identified 95 lateralized brain areas comprising five networks supporting visuospatial attention processes. Among them, we can find two large-scale networks: the ParietoFrontal and TemporoFrontal networks. We identify hubs playing a pivotal role in the intra-hemispheric interaction within visuospatial attentional networks. The rightward lateralized ParietoFrontal encompasses one hub, the inferior frontal sulcus, while the TemporoFrontal network encompasses two right hubs: the inferior frontal cortex (pars triangularis and the anterior insula) and the posterior part of the superior temporal sulcus. Together, 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.