Biology subjects

Bernhardt, B. C.

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

47 records · Page 3Linked to original sources

bioRxiv2021

An open MRI dataset for multiscale neuroscience

AO_SCPLOWBSTRACTC_SCPLOWMultimodal neuroimaging grants a powerful window into the structure and function of the human brain at multiple scales. Recent methodological and conceptual advances have enabled investigations of the interplay between large-scale spatial trends (also referred to as gradients) in brain microstructure and connectivity, offering an integrative framework to study multiscale brain organization. Here, we share a multimodal MRI dataset for Microstructure-Informed Connectomics (MICA-MICs) acquired in 50 healthy adults (23 women; 29.54{+/-}5.62 years) who underwent high-resolution T1-weighted MRI, myelin-sensitive quantitative T1 relaxometry, diffusion-weighted MRI, and resting-state functional MRI at 3 Tesla. In addition to raw anonymized MRI data, this release includes brain-wide connectomes derived from i) resting-state functional imaging, ii) diffusion tractography, iii) microstructure covariance analysis, and iv) geodesic cortical distance, gathered across multiple parcellation scales. Alongside, we share large-scale gradients estimated from each modality and parcellation scale. Our dataset will facilitate future research examining the coupling between brain microstructure, connectivity, and macroscale function. MICA-MICs is available on the Canadian Open Neuroscience Platforms data portal (https://portal.conp.ca).

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bioRxiv2021

Genetic and phylogenetic uncoupling of structure and function in human transmodal cortex

Brain structure scaffolds intrinsic function, supporting cognition and ultimately behavioral flexibility. However, it remains unclear how a static, genetically controlled architecture supports flexible cognition and behavior. Here, we synthesize genetic, phylogenetic and cognitive analyses to understand how the macroscale organization of structure-function coupling across the cortex can inform its role in cognition. In humans, structure-function coupling was highest in regions of unimodal cortex and lowest in transmodal cortex, a pattern that was mirrored by a reduced alignment with heritable connectivity profiles. Structure-function uncoupling in non-human primates had a similar spatial distribution, but we observed an increased coupling between structure and function in association regions in macaques relative to humans. Meta-analysis suggested regions with the least genetic control (low heritable correspondence and different across primates) are linked to social cognition and autobiographical memory. Our findings establish the genetic and evolutionary uncoupling of structure and function in different transmodal systems may support the emergence of complex, culturally embedded forms of cognition.

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bioRxiv2021

Functional architecture of the aging brain

The intrinsic functional organization of the brain changes into older adulthood. Age differences are observed at multiple spatial scales, from global reductions in modularity and segregation of distributed brain systems, to network-specific patterns of dedifferentiation. Whether dedifferentiation reflects an inevitable, global shift in brain function with age, circumscribed, experience dependent changes, or both, is uncertain. We employed a multi-method strategy to interrogate dedifferentiation at multiple spatial scales. Multi-echo (ME) resting-state fMRI was collected in younger (n=181) and older (n=120) healthy adults. Cortical parcellation sensitive to individual variation was implemented for precision functional mapping of each participant, while preserving group-level parcel and network labels. ME-fMRI processing and gradient mapping identified global and macroscale network differences. Multivariate functional connectivity methods tested for microscale, edge-level differences. Older adults had lower BOLD signal dimensionality, consistent with global network dedifferentiation. Gradients were largely age-invariant. Edge-level analyses revealed discrete, network-specific dedifferentiation patterns in older adults. Visual and somatosensory regions were more integrated within the functional connectome; default and frontoparietal control network regions showed greater connectivity; and the dorsal attention network was more integrated with heteromodal regions. These findings highlight the importance of multi-scale, multi-method approaches to characterize the architecture of functional brain aging.

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bioRxiv2020

A low-dimensional connectome manifold governs the organization and plasticity of social brain functions in humans.

The human brain scaffolds social cognitive functions, including Theory of Mind, empathy and compassion, through its functional and microstructural organization. However, it remains unclear how the learning and refinement of these skills may, in turn, shape brain function and structure. Here we studied if different types of social mental training can lead to plastic changes in brain function and microstructure. We studied a group of 332 healthy adults (197 women, 20-55 years) with repeated multimodal neuroimaging and behavioral testing. Our neuroimaging approach capitalized on the quantification of cortical functional gradients and myelin-sensitive T1 relaxometry, two emerging measures of cortical functional organization and microstructure. Longitudinal analysis indicated marked changes in intrinsic cortical function and microstructure, which varied as a function of social training content. In particular, we observed consistent differential change in function and microstructure between attention-mindfulness and socio-cognitive training in regions functionally associated with attention and interoception, including insular and parietal cortices. Conversely, socio-affective and socio-cognitive training resulted in differential microstructural changes in regions classically implicated in interoceptive and emotional processing, including insular and orbitofrontal areas, but did not result in functional reorganization. Notably, longitudinal changes in cortical function and microstructure were predictive of behavioral change in attention, compassion and perspective-taking, suggesting behavioral relevance. In sum, our work provides evidence for functional and microstructural plasticity after the training of social-interoceptive functions, and provides a causal perspective on the neural basis of behavioral adaptation in human adults.

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bioRxiv2020

Multiscale communication in cortico-cortical networks

Signaling in brain networks unfolds over multiple topological scales. Areas may exchange information over local circuits, encompassing direct neighbours and areas with similar functions, or over global circuits, encompassing distant neighbours with dissimilar functions. Here we study how the organization of cortico-cortical networks mediate localized and global communication by parametrically tuning the range at which signals are transmitted on the white matter connectome. By investigating the propensity for brain areas to communicate with their neighbors across multiple scales, we naturally reveal their functional diversity. We find that unimodal regions show preference for local communication and multimodal regions show preferences for global communication. We show that these preferences manifest as region- and scale-specific structure-function coupling. Namely, the functional connectivity of unimodal regions emerges from monosynaptic communication in small-scale circuits, while the functional connectivity of transmodal regions emerges from polysynaptic communication in large-scale circuits. Altogether, the present findings reveal how functional hierarchies emerge from hidden but highly structured multiscale connection patterns.

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bioRxiv2020

Topographic gradients of intrinsic dynamics across neocortex

The intrinsic dynamics of neuronal populations are shaped by both macroscale connectome architecture and microscale attributes. Neural activity arising from the interplay of these local and global factors therefore varies from moment to moment, with rich temporal patterns. Here we comprehensively characterize intrinsic dynamics throughout the human brain. Applying massive temporal feature extraction to regional haemodynamic activity, we estimate over 6,000 statistical properties of individual brain regions time series across the neocortex. We identify two robust topographic gradients of intrinsic dynamics, one spanning a ventromedial-dorsolateral axis and the other spanning a unimodal-transmodal axis. These gradients are distinct in terms of their temporal composition and reflect spatial patterns of microarray gene expression, intracortical myelin and cortical thickness, as well as structural and functional network embedding. Importantly, these gradients are closely correlated with patterns of functional activation, differentiating cognitive versus affective processing and sensory versus higher-order cognitive processing. Altogether, these findings demonstrate a link between microscale and macroscale architecture, intrinsic dynamics, and cognition.

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bioRxiv2020

Shaping Brain Structure: Genetic and Phylogenetic Axes of Macro Scale Organization of Cortical Thickness

Structural and functional characteristics of the cortex systematically vary along global axes as a function of cytoarchitecture, gene expression, and connectivity. The topology of the cerebral cortex has been proposed to be a prerequisite for the emergence of human cognition and explain both the impact and progression of pathology. However, the neurogenetic origin of these organizational axes in humans remains incompletely understood. To address this gap in the literature our current study assessed macro scale cortical organization through an unsupervised machine learning analysis of cortical thickness covariance patterns and used converging methods to evaluate its genetic basis. In a large-scale sample of twins (n=899) we found structural covariance of thickness to be organized along both an anterior-to-posterior and inferior-to-superior axis. We found that both axes showed a high degree of correspondence in pairs of identical twins, suggesting a strong heritable component in humans. Furthermore, comparing these dimensions in macaques and humans highlighted similar organizational principles in both species demonstrating that these axes of cortical organization are phylogenetically conserved within primate species. Finally, we found that in both humans and macaques the inferior-superior dimension of cortical organization was aligned with the predictions of the dual-origin theory, highlighting the possibility that the macroscale organization of primate brain structure is subject to multiple distinct neurodevelopmental trajectories. Together, our study establishes the genetic basis of natural axes in the cerebral cortex along which structure is organized and so provides important insights into the organization of human cognition that will inform both our understanding of how structure guides function and for the progression of pathology in diseases.

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bioRxiv2019

Neurocognitive patterns dissociating semantic processing from executive control are linked to more detailed off-task mental time travel

1Features of ongoing experience are common across individuals and cultures. However, certain people express specific patterns to a greater extent than others. The current psychological theory assumes that individual differences in thought patterns occur because different types of experience depend on differences in associated neurocognitive mechanisms. Consequently, individual variation in the underlying neurocognitive architecture is hypothesised to determine the ease with which certain thought patterns are generated or maintained. Our study (N=178) tested this hypothesis using multivariate pattern analysis to infer shared variance among measures of cognitive function and neural organisation and examined whether these hidden structures explain reports of the patterns of on-going thoughts people experienced in the lab. We found that relatively better performance on tasks requiring primarily semantic knowledge, rather than executive control, was linked to a neural functional organisation that was associated, via meta-analysis, with task labels related to semantic associations (sentence processing, reading and verbal semantics). Variability of this functional mode predicted significant individual variation in the types of thoughts that individuals experienced in the laboratory: Neurocognitive patterns linked to better performance at tasks that required guidance from semantic representation, rather than those dependent on executive control, were associated with patterns of thought characterised by greater subjective detail and a focus on time periods other than the here and now. These relationships were consistent across different days and did not vary with task condition, indicating they are relatively stable features of an individuals cognitive profile. Together these data confirm that individual variation in aspects of ongoing experience can be inferred from hidden neurocognitive architecture and demonstrate that performance trade-offs between executive control and long term semantic knowledge are linked to a persons tendency to imagine situations that transcend the here and now.

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bioRxiv2019

A moment of change: shifts in myeloarchitecture characterise adolescent development of cortical gradients

The biological processes underpinning adolescent brain maturation remain elusive. Expanding on previous work showing age-related changes in cortical morphology, we studied an accelerated longitudinal cohort of adolescents and young adults (n=223, two time points) to investigate dynamic reconfigurations in myeloarchitecture. Intracortical profiles were generated using magnetization transfer (MT) data, a myelin-sensitive magnetic resonance imaging contrast. Mixed-effect models of depth specific intracortical profiles demonstrated two separate processes i) related to overall increases in MT, and ii) showing a flattening of the MT profile related to enhanced signal in mid-to-deeper layers, especially in heteromodal and unimodal association cortices. This development was independent of morphological changes, and enhanced MT in mid-to-deeper layers was found to spatially co-localise specifically with gene expression markers of oligodendrocytes. Covariance analysis between all pairs of intracortical profiles revealed that these intracortical changes contributed to a gradual and dynamic differentiation from higher-order to lower-order systems. Depth-dependent trajectories of intracortical myeloarchitectural development contribute to the maturation of structural hierarchies in the human neocortex, providing a model for adolescent development that bridges microstructural and macroscopic scales of brain organization.\n\neLife digestIntracortical myelin imposes a spatial structure on cortico-cortical connections, yet little is known about how myeloarchitecture develops throughout youth. We formulated a novel approach to study cortical myeloarchitecture in individual humans and leveraged an accelerated longitudinal design to track age-related changes from 14-27 years. We discovered two unique processes: one involving increasing mean myelin and another characterised by the preferential accumulation of myelin in mid-to-deeper cortical layers. Both processes contributed to an increasing segregation of lower-order from higher-order systems along the macroscale cortical hierarchy. These findings illustrate how layer specific microstructural changes contribute to the maturation of cortical organization and suggest adolescent fine tuning of hierarchical gradients of cortical networks.

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bioRxiv2019

Multidimensional Associations between Cognition and Connectome Organization in Temporal Lobe Epilepsy

AO_SCPLOWBSTRACTC_SCPLOWO_ST_ABSOO_SCPLOWBJECTIVEC_SCPLOWC_ST_ABSTemporal lobe epilepsy (TLE) is known to affect large-scale structural networks and cognitive function in multiple domains. The study of complex relations between structural network organization and cognition requires comprehensive analytical methods and a shift towards multivariate techniques. The current work sought to identify multidimensional associations between cognitive performance and structural network topology in TLE.\n\nMO_SCPLOWETHODSC_SCPLOWWe studied 34 drug-resistant TLE patients and 25 age- and sex-matched healthy controls. All participants underwent a comprehensive neurocognitive battery and multimodal MRI, allowing for large-scale connectomics, and morphological evaluation of subcortical and neocortical regions. Using canonical correlation analysis, we identified a multivariate mode that links cognitive performance to a brain structural network. Our approach was complemented by bootstrap-based clustering to derive cognitive subtypes and associated patterns of macroscale connectome anomalies.\n\nRO_SCPLOWESULTSC_SCPLOWBoth methodologies provided converging evidence for a close coupling between cognitive impairments across multiple domains and large-scale structural network compromise. Cognitive classes presented with an increasing gradient of abnormalities (increasing cortical and subcortical atrophy and less efficient white matter connectome organization in patients with increasing degrees of cognitive impairments). Notably, network topology characterized better the cognitive performance than morphometric measures. Thus, connectome characteristics featured as important markers of network reorganization and loss of inter-regional connectivity.\n\nCO_SCPLOWONCLUSIONSC_SCPLOWThe multivariate approach emphasized the close interplay between cognitive impairment and large-scale network anomalies in TLE. Our findings contribute to understand the complexity of structural connectivity regulating the heterogeneous cognitive deficits found in epilepsy

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bioRxiv2018

A systems-level analysis highlights microglial activation as a modifying factor in common forms of human epilepsy

The common human epilepsies are associated with distinct patterns of reduced cortical thickness, detectable on neuroimaging, with important clinical consequences. To explore underlying mechanisms, we layered MRI-based cortical structural maps from a large-scale epilepsy neuroimaging study onto highly spatially-resolved human brain gene expression data, identifying >2,500 genes overexpressed in regions of reduced cortical thickness, compared to relatively-protected regions. The resulting set of differentially-expressed genes shows enrichment for microglial markers, and in particular, activated microglial states. Parallel analyses of cell-specific eQTLs show enrichment in human genetic signatures of epilepsy severity, but not epilepsy causation. Post mortem brain tissue from humans with epilepsy shows excess activated microglia. In an experimental model, depletion of activated microglia prevents cortical thinning, but not the development of chronic seizures. These convergent data strongly implicate activated microglia in cortical thinning, representing a new dimension for concern and disease modification in the epilepsies, potentially distinct from seizure control.

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