Biology subjects

Bernhardt, B. C.

Publications and source records attributed to Bernhardt, B. C..

At least 37 records · Page 2Linked to original sources

bioRxiv2024

Microstructural asymmetry in the human cortex

While macroscale brain asymmetry and its relevance for human cognitive function have been consistently shown, the underlying neurobiological signatures remain an open question. Here, we probe layer-specific microstructural asymmetry of the human cortex using intensity profiles from post-mortem cytoarchitecture. An anterior-posterior cortical pattern of left-right asymmetry was found, varying across cortical layers. A similar anterior-posterior pattern was observed using in vivo microstructural imaging, with in vivo asymmetry showing the strongest similarity with layer III. Microstructural asymmetry varied as a function of age and sex and was found to be heritable. Moreover, asymmetry in microstructure corresponded to asymmetry of intrinsic function, in particular in sensory areas. Last, probing the behavioral relevance, we found differential association of language and markers of mental health with asymmetry, illustrating a functional divergence between inferior-superior and anterior-posterior microstructural axes anchored in microstructural development. Our study highlights the layer-based patterning of microstructural asymmetry of the human cortex and its functional relevance.

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bioRxiv2024

MULTIMODAL GRADIENTS UNIFY LOCAL AND GLOBAL CORTICAL ORGANIZATION

AO_SCPLOWBSTRACTC_SCPLOWSpecialization of brain areas and subregions, as well as their integration into large-scale networks are key principles in neuroscience. Consolidating both local and global cortical organization, however, remains challenging. Our study developed a new approach to map global cortex-wise similarities of microstructure, structural connectivity, and functional interactions, and integrate these patterns with maps of cortical arealization. Our analysis combined repeated high-field in-vivo 7 tesla (7T) Magnetic Resonance Imaging (MRI) data collected in 10 healthy adults with a recently introduced probabilistic post-mortem atlas of cortical cytoarchitecture. We obtained multimodal eigenvectors describing cortex-wide gradients at the level of microstructural covariance, structural connectivity, and intrinsic functional interactions, and then assessed inter- and intra-area differences in cortex-wide embedding based on these multimodal eigenvectors. Inter-area similarities followed a canonical sensory-fugal gradient, with primary sensorimotor cortex being the most distinctive from all other areas, while paralimbic regions were least distinctive. This pattern largely corresponded to functional connectivity variations across different tasks collected in the same participants, suggesting that the degree of global cortical integration mirrors the functional diversity of brain areas across contexts. When studying heterogeneity within areas, we did not observe a similar relationship, despite overall higher heterogeneity in association cortices relative to paralimbic and idiotypic cortices. The results were replicated in a different dataset. Our findings highlight a close coupling between cortical arealization and global cortical motifs in shaping specialized versus integrative human brain function. SO_SCPLOWIGNIFICANCEC_SCPLOWOur work situates cytoarchitecture-derived cortical areas within multimodal gradients of cortical microstructure, connectivity, and function derived from high-definition multimodal neuroimaging. We demonstrated that primary sensory and motor areas show most distinctive gradient profiles while paralimbic areas were least distinctive, overall recapitulating a sensory-fugal axis. This axis was shown to relate to the diversity of cortical areas across different functional contexts, and findings could be replicated across an independent dataset. Overall, our work shows how frameworks of cortical arealization and macroscale gradients converge in shaping functional specialization versus integration in the human brain.

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bioRxiv2024

HippoMaps: Multiscale cartography of the human hippocampal formation

The hippocampus has a unique microarchitecture, is situated at the nexus of multiple macroscale functional networks, contributes to numerous cognitive as well as affective processes, and is highly susceptible to brain pathology across common disorders. These features make the hippocampus a model to understand how brain structure covaries with function, in both health and disease. Here, we introduce HippoMaps, an open access toolbox and online data warehouse for the mapping and contextualization of subregional hippocampal data in the human brain (http://hippomaps.readthedocs.io). HippoMaps capitalizes on a unified hippocampal unfolding approach as well as shape intrinsic registration capabilities to allow for cross-subject and cross-modal data aggregation. We initialize this repository with an unprecedented combination of hippocampal data spanning 3D ex-vivo histology, ex-vivo 9.4 Tesla MRI, as well as in-vivo structural MRI and resting-state functional MRI (rsfMRI) obtained at 3 and 7 Tesla, together with intracranial encephalography (iEEG) recordings in epilepsy patients. HippoMaps also contains validated tools for spatial map association analysis in the hippocampus that correct for autocorrelation. All code and data are compliant with community standards, and comprehensive online tutorials facilitate broad adoption. Applications of this work span methodologies and modalities, spatial scales, as well as clinical and basic research contexts, and we encourage community feedback and contributions in the spirit of open and iterative scientific resource development.

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bioRxiv2024

A Multimodal Characterization of Low-Dimensional Thalamocortical Structural Connectivity Patterns

The human thalamus is a bilateral and heterogeneous grey matter structure that plays a crucial role in coordinating whole-brain activity. Investigations of its complex structural and functional internal organization revealed to a certain degree overlapping parcellations, however, a consensus on thalamic subnuclei boundaries remains absent. Recent work suggests that thalamic organization might additionally reflect continuous axes transcending nuclear boundaries. In this study, we used a multimodal approach to uncover how low-dimensional axes that describe thalamic connectivity patterns to the cortex are related to internal thalamic microstructural features, functional connectivity, and structural covariance. We computed a thalamocortical structural connectome via probabilistic tractography on diffusion MRI and derived two main axes of thalamic organization. The principal thalamic gradient, extending from medial to lateral and differentiating between transmodal and unimodal nuclei, was related to intrathalamic myelin profiles, and patterns of functional connectivity, while the secondary axis showed correspondence to core-matrix cell type distributions. Lastly, exploring multimodal thalamocortical associations on a global scale, we observed that the medial-to- lateral gradient consistently differentiated limbic, frontoparietal, and default mode network nodes from dorsal and ventral attention networks across modalities. However, the link with sensory modalities varied. In sum, we show the coherence between lower dimensional patterns of thalamocortical structural connectivity and various modalities, shedding light on multiscale thalamic organization.

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bioRxiv2023

Hippocampal connectivity patterns echo macroscale cortical evolution in the primate brain

The hippocampus is involved in numerous cognitive functions, some of which have uniquely human aspects, such as autobiographical memory. Hippocampal anatomy, however, is typically considered conserved across primates and its evolutionary diversification is rarely studied. Comparing hippocampal structure and function is, therefore, critical for understanding human brain architecture. Here, we developed a novel comparative framework to study the hippocampus across species characterising its geometry, microstructure, and functional network embedding. In humans and macaques, we generated a new comparative space that represents the hippocampus as an unfolded surface, which respects its sheet-like anatomy. We mapped histological and MRI-derived markers of microstructure to the hippocampal surface and integrated it with low-dimensional embedding of resting-state MRI connectivity data. Our results demonstrate that the micro- and macro-structural organisation of the hippocampus are overall conserved in both species, showing consistent anterior-posterior and subfield-to-subfield differentiation. Furthermore, while hippocampal functional organisation also follows anterior-posterior trends in both species, hippocampal functional connectivity markedly reflected evolutionary reconfiguration of transmodal networks, in particular the default-mode network. Specifically, the inferior parietal lobe in the macaque mirrors an incomplete integration of the default mode network in non-human primates. By combining fine-grained anatomical investigation with large-scale functional imaging, we showed that microstructurally preserved regions like the hippocampus may still undergo functional reconfiguration, due to their embedding in higher-order association networks. SummaryWhile the hippocampus is key for uniquely human cognitive abilities, it is also a phylogenetically old cortex and paradoxically considered evolutionarily preserved. Here, we introduce a comparative framework to quantify preservation and reconfiguration of hippocampal organisation in primate evolution, by analysing the hippocampus as an unfolded cortical surface that is geometrically matched across species. Our findings revealed an overall conservation of hippocampal macro- and micro-structure, showing anterior-posterior and, perpendicularly, subfield-related organisational axes in both humans and macaques. However, while functional organisation in both species also followed an anterior-posterior axis, the latter showed a marked evolutionary reconfiguration, which mirrors a rudimentary integration of the default-mode-network in non-human primates. Our findings suggest that microstructurally preserved regions like the hippocampus may still undergo functional reconfiguration in primate evolution, due to their embedding in heteromodal association networks.

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bioRxiv2023

Cerebral perfusion alterations in temporal lobe epilepsy: Structural underpinnings and network disruptions

AO_SCPLOWBSTRACTC_SCPLOWO_ST_ABSOO_SCPLOWBJECTIVEC_SCPLOWC_ST_ABSNeuroimaging has been the prevailing method to study brain networks in temporal lobe epilepsy (TLE), showing widespread alterations beyond the mesiotemporal lobe. Despite the critical role of the cerebrovascular system in maintaining whole-brain structure and function, changes in cerebral blood flow (CBF) remain incompletely understood in the disease. MO_SCPLOWETHODSC_SCPLOWWe studied 24 individuals with pharmaco-resistant TLE and 38 healthy adults using multimodal 3T magnetic resonance imaging. We compared regional CBF changes in patients relative to controls and related our perfusion findings to morphological and microstructural metrics. We further probed inter-regional vascular networks in TLE, using graph theoretical CBF covariance analysis. Finally, we assessed the effects of disease duration to study progressive changes. RO_SCPLOWESULTSC_SCPLOWCompared to controls, individuals with TLE showed widespread CBF reductions, predominantly in fronto-temporal regions, with 83% of patients showing more marked decreases ipsilateral than contralateral to the seizure focus. Parallel structural profiling and network-based models showed that cerebral hypoperfusion may be partly constrained by grey and white matter changes and topologically segregated from whole-brain perfusion networks. Negative effects of progressive disease duration further targeted regional CBF profiles in patients. Findings were confirmed in a subgroup of patients who remained seizure-free after surgery. IO_SCPLOWNTERPRETATIONC_SCPLOWOur multimodal findings provide insights into vascular contributions to TLE pathophysiology and highlight their clinical potential in seizure lateralization.

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bioRxiv2023

Pervasive inter-individual differences in the sensorimotor-association axis of cortical organization

In humans, many neurobiological features of the cortex--including gene expression patterns, microstructure, and functional connectivity--vary systematically along a sensorimotor-association (S-A) axis of brain organisation. To date, it is still poorly understood whether inter-individual differences in patterns of S-A axis capture these robust spatial relationships across neurobiological properties observed at the group-level. Here, we examine inter-individual differences in structural and functional properties of the S-A axis, namely cortical microstructure, geodesic distances, and the functional gradient, in a sample of young adults from the Human Connectome Project (N = 992, including 328 twins). We quantified heritable variation associated with inter-individual differences in the S-A axis, and assessed whether structural and functional properties that are highly spatially correlated at the group-level also share genetic underpinnings. To consider measurement errors in resting-state functional connectivity data and their impact on properties of the S-A axis, we used a multivariate twin design capable of disentangling individual-level variation in both intra- and inter-individual differences. After accounting for some of the intra-individual variation, we found average heritable individual differences in both the functional gradient (htwin2 = 57%), cortical microstructure (htwin2 = 43%), and geodesic distances (htwin2 = 34%). However, these genetic influences were mostly distinct and deviated from group-level patterns. In particular, we found no significant genetic correlation between the functional gradient and microstructure, while we found both positive and negative genetic associations between the functional gradient and geodesic distances. Our approach highlights the complexity of genetic contributions to brain organisation and may have potential implications for understanding cognitive variability within the S-A axis framework.

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bioRxiv2023

Diverging asymmetry of intrinsic functional organization in autism

Autism is a neurodevelopmental condition involving atypical sensory-perceptual functions together with language and socio-cognitive deficits. Previous work has reported subtle alterations in the asymmetry of brain structure and reduced laterality of functional activation in individuals with autism relative to non-autistic individuals (NAI). However, whether functional asymmetries show altered intrinsic systematic organization in autism remains unclear. Here, we computed inter- and intra-hemispheric asymmetry of intrinsic functional gradients capturing connectome organization along three axes, stretching between sensory-default, somatomotor-visual, and default-multiple demand networks, to study system-level hemispheric imbalances in autism. We observed decreased leftward functional asymmetry of language network organization in individuals with autism, relative to NAI. Whereas language network asymmetry varied across age groups in NAI, this was not the case in autism, suggesting atypical functional laterality in autism may result from altered developmental trajectories. Finally, we observed that intra-but not inter-hemispheric features were predictive of the severity of autistic traits. In sum, our findings illustrate how regional and patterned functional lateralization is altered in autism at the system level. Such differences may be rooted in altered developmental trajectories of functional organization asymmetry in autism.

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bioRxiv2023

Hippocampal subfield CA1-3 shows differential structural and functional network plasticity after stress-reducing socio-affective mental training

The hippocampus is a central modulator of the HPA-axis, impacting the regulation of stress on brain structure, function, and behavior. The current study assessed whether three different types of 3-months mental Training Modules geared towards nurturing a) attention-based mindfulness, b) socio-affective or c) socio-cognitive skills may impact hippocampal organization by reducing stress. We evaluated mental training-induced changes in hippocampal subfield volume and intrinsic functional connectivity, by combining longitudinal structural and resting-state fMRI connectivity analysis in 332 healthy adults. We related these changes to changes in diurnal and chronic cortisol levels. We observed increases in bilateral cornu ammonis volume (CA1-3) following the 3-months compassion-based module targeting socio-affective skills (Affect module), as compared to socio-cognitive skills (Perspective module) or a waitlist cohort with no training intervention. Structural changes were paralleled by relative increases in functional connectivity of CA1-3 when fostering socio-affective as compared to socio-cognitive skills. Furthermore, training-induced changes in CA1-3 structure and function consistently correlated with reductions in cortisol output. Notably, using a multivariate approach, we found that other subfields that did not show group-level changes also contributed to changes in cortisol levels. Overall, we provide a link between a socio-emotional behavioural intervention, changes in hippocampal subfield structure and function, and reductions in cortisol in healthy adults.

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bioRxiv2023

Whole-brain structural connectome asymmetry in autism

AO_SCPLOWBSTRACTC_SCPLOWAutism spectrum disorder is a common neurodevelopmental condition that manifests as a disruption in sensory and social skills. Although it has been shown that the brain morphology of individuals with autism is asymmetric, how this differentially affects the structural connectome organization of each hemisphere remains under-investigated. We studied whole-brain structural connectivity-based brain asymmetry in 47 individuals with autism and 37 healthy controls using diffusion magnetic resonance imaging obtained from the Autism Brain Imaging Data Exchange initiative. By leveraging dimensionality reduction techniques, we constructed low-dimensional representations of structural connectivity and calculated their asymmetry index. We compared the asymmetry index between individuals with autism and neurotypical controls and found atypical structural connectome asymmetry in the sensory, default-mode, and limbic networks and the caudate in autism. Network communication provided topological underpinnings by demonstrating that the temporal and dorsolateral prefrontal regions showed reduced global network communication efficiency and decreased send-receive network navigation in the caudate region in individuals with autism. Finally, supervised machine learning revealed that structural connectome asymmetry is associated with communication-related autistic symptoms and nonverbal intelligence. Our findings provide insights into macroscale structural connectome alterations in autism and their topological underpinnings.

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bioRxiv2022

Cortical microstructural gradients capture memory network reorganization in temporal lobe epilepsy

Temporal lobe epilepsy (TLE), one of the most common pharmaco-resistant epilepsies, is associated with pathology of paralimbic brain regions, particularly in the mesiotemporal lobe. Cognitive dysfunction in TLE is frequent, and particularly affects episodic memory. Crucially, these difficulties challenge the quality of life of patients, sometimes more than seizures, underscoring the need to assess neural processes of cognitive dysfunction in TLE to improve patient management. Our work harnessed a novel conceptual and analytical approach to assess spatial gradients of microstructural differentiation between cortical areas based on high-resolution MRI analysis. Gradients track region-to-region variations in intracortical lamination and myeloarchitecture, serving as a system-level measure of structural and functional reorganization. Comparing cortex-wide microstructural gradients between 21 patients and 35 healthy controls, we observed a contracted gradient in TLE driven by reduced microstructural differentiation between paralimbic cortices and the remaining cortex with marked abnormalities in ipsilateral temporopolar and dorsolateral prefrontal regions. Findings were replicated in an independent cohort. Using an independent post mortem dataset, we observed that in vivo findings reflected topographical variations in cortical lamination patterns, confirming that TLE-related changes in the microstructural gradient reflected increased proximity of regions with more dissimilar laminar structure. Disease-related transcriptomics could furthermore show specificity of our findings to TLE over other common epilepsy syndromes. Finally, microstructural dedifferentiation was associated with cognitive network reorganization seen during an episodic memory functional MRI paradigm, and correlated with inter-individual differences in task accuracy. Collectively, our findings showing a pattern of reduced microarchitectural differentiation between paralimbic regions and the remaining cortex provide a parsimonious explanation for functional network reorganization and cognitive dysfunction characteristic of TLE.

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bioRxiv2022

Comparison Between Gradients and Parcellations for Functional Connectivity Prediction of Behavior

Resting-state functional connectivity (RSFC) is widely used to predict behavioral measures. To predict behavioral measures, representing RSFC with parcellations and gradients are the two most popular approaches. Here, we compare parcellation and gradient approaches for RSFC-based prediction of a broad range of behavioral measures in the Human Connectome Project (HCP) and Adolescent Brain Cognitive Development (ABCD) datasets. Among the parcellation approaches, we consider group-average "hard" parcellations (Schaefer et al., 2018), individual-specific "hard" parcellations (Kong et al., 2021a), and an individual-specific "soft" parcellation (spatial independent component analysis with dual regression; Beckmann et al., 2009). For gradient approaches, we consider the well-known principal gradients (Margulies et al., 2016) and the local gradient approach that detects local RSFC changes (Laumann et al., 2015). Across two regression algorithms, individual-specific hard-parcellation performs the best in the HCP dataset, while the principal gradients, spatial independent component analysis and group-average "hard" parcellations exhibit similar performance. On the other hand, principal gradients and all parcellation approaches perform similarly in the ABCD dataset. Across both datasets, local gradients perform the worst. Finally, we find that the principal gradient approach requires at least 40 to 60 gradients to perform as well as parcellation approaches. While most principal gradient studies utilize a single gradient, our results suggest that incorporating higher order gradients can provide significant behaviorally relevant information. Future work will consider the inclusion of additional parcellation and gradient approaches for comparison.

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bioRxiv2022

NEUROTRANSMITTER TRANSPORTER/RECEPTOR CO-EXPRESSION SHARES ORGANIZATIONAL TRAITS WITH BRAIN STRUCTURE AND FUNCTION

The relationship between brain areas based on neurotransmitter receptor and transporter molecule expression patterns may provide a link between brain structure and its function. Here, we studied the organization of the receptome, a measure of regional neurotransmitter receptor/transporter molecule (NTRM) similarity, derived from in vivo PET imaging studies of 19 different receptors and transporters. Nonlinear dimensionality reduction revealed three main spatial gradients of receptor similarity in the cortex. The first gradient differentiated the somato-motor network from the remaining cortex. The second gradient spanned between temporo-occipital and frontal anchors, differentiating visual and limbic networks from attention and control networks, and the third receptome gradient was anchored between the occipital and temporal cortices. In subcortical structures, the receptome delineated a striato-thalamic axis, separating functional communities. Moreover, we observed similar organizational principles underlying receptome differentiation in cortex and subcortex, indicating a link between subcortical and cortical NTRM patterning. Overall, we found that the cortical receptome shared key organizational traits with brain structure and function. Node-level correspondence of receptor similarity to functional, microstructural, and diffusion MRI-based measures decreased along a primary-to-transmodal gradient. Compared to primary and paralimbic regions, we observed higher receptomic diversification in unimodal and heteromodal regions, possibly supporting functional flexibility. In sum, we show how receptor similarity may form an additional organizational layer of human brain architecture, bridging brain structure and function.

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bioRxiv2022

Assortative mixing in micro-architecturally annotated brain connectomes

The wiring of the brain connects micro-architecturally diverse neuronal populations. The conventional graph model encodes macroscale brain connectivity as a network of nodes and edges, but abstracts away the rich biological detail of each regional node. Regions are different in terms of their microscale attributes, many of which are readily available through modern technological advances and data-sharing initiatives. How is macroscale connectivity related to nodal attributes? Here we investigate the systematic arrangement of white-matter connectivity with respect to multiple biological annotations. Namely, we formally study assortative mixing in annotated connectomes by quantifying the tendency for regions to be connected with each other based on the similarity of their micro-architectural attributes. We perform all experiments using four cortico-cortical connectome datasets from three different species (human, macaque and mouse), and consider a range of molecular, cellular and laminar annotations, including gene expression, neurotransmitter receptors, neuron density, laminar thickness and intracortical myelin. Importantly, we disentangle the relationship between neural wiring, regional heterogeneity and spatial embedding using spatial autocorrelation-preserving null models. We show that mixing between micro-architecturally diverse neuronal populations is supported by long-distance connections. Using meta-analytic decoding, we find that the arrangement of connectivity patterns with respect to biological annotations shape patterns of regional functional specialization. Specifically, regions that connect to biologically similar regions are associated with executive function; conversely, regions that connect with biologically dissimilar regions are associated with memory function. By bridging scales of cortical organization, from microscale attributes to macroscale connectivity, this work lays the foundation for next-generation annotated connectomics.

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bioRxiv2021

Heritability of hippocampal functional and microstructural organisation

The hippocampus is a uniquely infolded allocortical structure in the medial temporal lobe that consists of the microstructurally and functionally distinct subregions: subiculum, cornu ammonis, and dentate gyrus. The hippocampus is a remarkably plastic region that is implicated in learning and memory. At the same time it has been shown that hippocampal subregion volumes are heritable, and that genetic expression varies along a posterior to anterior axis. Here, we studied how a heritable, stable, hippocampal organisation may support its flexible function in healthy adults. Leveraging the twin set-up of the Human Connectome Project with multimodal neuroimaging, we observed that the functional connectivity between hippocampus and cortex was heritable and that microstructure of the hippocampus genetically correlated with cortical microstructure. Moreover, both functional and microstructural organisation could be consistently captured by anterior-to-posterior and medial-to-lateral axes across individuals. However, heritability of functional, relative to microstructural, organisation was found reduced, suggesting individual variation in functional organisation of subfields is under low genetic control. Last, we demonstrate that structure and function couple along its genetic axes, suggesting an interplay of stability and plasticity within the hippocampus. Our study provides new insights on the heritability of the hippocampal formation and illustrates how genetic axes may scaffold hippocampal structure and function.

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bioRxiv2021

Asymmetry of cortical functional hierarchy in humans and macaques suggests phylogenetic conservation and adaptation

The human cerebral cortex is symmetrically organized along large-scale axes but also presents inter-hemispheric differences in structure and function. The quantified contralateral homologous difference, i.e., asymmetry, is a key feature of the human brain left-right axis supporting functional processes, such as language. Here, we assessed whether the asymmetry of cortical functional organization is heritable and phylogenetically conserved between humans and macaques. Our findings indicate asymmetric organization along an axis describing a hierarchical functional trajectory from perceptual/action to abstract cognition. Whereas language network showed leftward asymmetric organization, frontoparietal network showed rightward asymmetric organization. These asymmetries were heritable and comparable between humans and macaques, suggesting (phylo)genetic conservation. However, both language and frontoparietal networks showed a qualitatively larger asymmetry in humans relative to macaques and variable heritability in humans. This may reflect an evolutionary adaptation allowing for experience-dependent specialization, linked to higher-order cognitive functions uniquely developed in humans.

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bioRxiv2021

Multilevel neural gradients reflect transdiagnostic effects of major psychiatric conditions on cortical morphology

AO_SCPLOWBSTRACTC_SCPLOWIt is increasingly recognized that multiple psychiatric conditions are underpinned by shared neural pathways, affecting similar brain systems. Here, we assessed i) shared dimensions of alterations in cortical morphology across six major psychiatric conditions (autism spectrum disorder, attention deficit/hyperactivity disorder, major depression, obsessive-compulsive disorder, bipolar disorder, schizophrenia) and ii) carried out a multiscale neural contextualization, by cross-referencing shared anomalies against cortical myeloarchitecture and cytoarchitecture, as well as connectome and neurotransmitter organization. Pooling disease-related effects on MRI-based cortical thickness measures across six ENIGMA working groups, including a total of 28,546 participants (12,876 patients and 15,670 controls), we computed a shared disease dimension on cortical morphology using principal component analysis that described a sensory-fugal pattern with paralimbic regions showing the most consistent abnormalities across conditions. The shared disease dimension was closely related to cortical gradients of microstructure and intrinsic connectivity, as well as neurotransmitter systems, specifically serotonin and dopamine. Our findings embed the shared effects of major psychiatric conditions on brain structure in multiple scales of brain organization and may provide novel insights into neural mechanisms into transdiagnostic vulnerability.

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bioRxiv2021

Long-range connections mirror and link microarchitectural and cognitive hierarchies in the human brain

AO_SCPLOWBSTRACTC_SCPLOWCore features of higher-order cognition are hypothesized to be implemented via distributed cortical networks that are linked via long-range connections. However, these connections are biologically expensive, and it is unknown how the computational advantages long-range connections provide overcome the associated wiring costs. Our study investigated this question by exploring the relationship between long-range functional connections and local cortical microarchitecture. Specifically, our work (i) profiled distant cortical connectivity using resting-state fMRI and cortico-cortical geodesic distance mapping, (ii) assessed how long-range connections reflect local brain microarchitecture, and (iii) studied the microarchitectural similarity of regions connected through long-range connections. Analysis of two independent datasets indicated that sensory and motor areas had more clustered short-range connectivity patterns, while transmodal association cortices, including regions of the default mode network, were characterized by distributed, long-range connections. Confirmatory meta-analysis suggested that this topographical difference mirrored a shift in cognitive function, from perception/action towards emotional and social cognitive processing. Analysis of myelin-sensitive in vivo MRI in the same participants as well as post mortem histology and gene expression established that gradients in functional connectivity distance are paralleled by those present in cortical microarchitecture. Moreover, long-range connections were found to link together spatially remote regions of association cortex with an unexpectedly similar microarchitecture. These findings provide novel insights into how the organization of distributed functional networks in transmodal association cortex contribute to cognition, because they suggest that long-range connections link together distant islands of association cortex with similar microstructural features.

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