Biology subjects

Vos de Wael, R.

Publications and source records attributed to Vos de Wael, R..

31 records · Page 2Linked to original sources

bioRxiv2020

Microstructural underpinnings and macroscale functional implications of temporal lobe connectivity gradients

AO_SCPLOWBSTRACTC_SCPLOWThe temporal lobe is implicated in higher cognitive processes and is one of the regions that underwent substantial reorganization during primate evolution. Its functions are instantiated, in part, by its complex layout of structural connections. This study identified low-dimensional representations of structural connectivity variations in human temporal cortex and explored their microstructural underpinnings and associations to macroscale function. We identified three eigenmodes which described gradients in structural connectivity. These gradients reflected interregional variations in cortical microstructure derived from quantitative MRI and post-mortem histology. Gradient-informed models accurately predicted macroscale measures of temporal lobe function. Gradients aligned closely with established measures of functional reconfiguration and areal expansion between macaques and humans, highlighting the important role evolution has played in shaping temporal lobe function. Our results provide robust evidence for three axes of structural connectivity in human temporal cortex with consistent microstructural underpinnings and contributions to large-scale brain network function.

neuroscience↗

bioRxiv2020

A structure-function substrate of memory for spatial configurations in medial and lateral temporal cortices

AO_SCPLOWBSTRACTC_SCPLOWPrior research has shown that structures of the mesiotemporal lobe, particularly the hippocampal-parahippocampal complex, are engaged in different forms of spatial cognition. Here, we developed a new paradigm, the Conformational Shift Spatial task (CSST), which examines the ability to encode and retrieve spatial relations between three unrelated items. This task is short, uses symbolic cues, and incorporates two difficulty levels and can be administered inside and outside the scanner. A cohort of 48 healthy young adults underwent the CSST, together with a set of validated behavioral measures and multimodal magnetic resonance imaging (MRI). Interindividual differences in CSST performance correlated with scores on an established spatial memory paradigm, but neither with episodic memory nor pattern separation performance, highlighting the specificity of the new measure. Analyzing high resolution structural MRI data, individuals with better spatial memory showed thicker medial as well as lateral temporal cortices. Functional relevance of these findings was supported by task-based functional MRI analysis in the same participants and ad hoc meta-analysis. Exploratory resting-state functional MRI analyses centered on clusters of morphological effects revealed additional modulation of intrinsic network integration, particularly between lateral and medial temporal structures. Our work presents a novel spatial memory paradigm and supports an integrated structure-function substrate in the human temporal lobe. Task paradigms are programmed in python and made open access.

neuroscience↗

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.

neuroscience↗

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.

neuroscience↗

bioRxiv2020

Topographic profiling of memory-related pattern separation processes in humans

AO_SCPLOWBSTRACTC_SCPLOWEpisodic memory is our ability to remember past events accurately. Pattern separation, the process of of orthogonalizing similar aspects of external information into nonoverlapping representations, is one of its mechanisms. Converging evidence suggests a pivotal role of the hippocampus, in concert with neocortical areas, in this process. The current study aimed to identify principal dimensions of functional activation associated with pattern separation in hippocampal and neocortical areas, in both healthy individuals and patients with lesions to the hippocampus. Administering a pattern separation fMRI paradigm to a group of healthy adults, we detected task-related activation in bilateral hippocampal and distributed neocortical areas. Capitalizing on manifold learning techniques applied to parallel resting-state fMRI data, we could identify that hippocampal and neocortical activity patterns were efficiently captured by their principal gradients of intrinsic functional connectivity, which follows the hippocampal long axis and sensory-fugal cortical organization. Functional activation patterns and their alignment with these principal dimensions were altered in patients. Notably, inter-individual differences in the concordance between task-related activity and intrinsic functional gradients were correlated with pattern separation performance in both patients and controls. Our work outlines a parsimonious approach to capture the functional underpinnings of episodic memory processes at the systems level, and to decode functional reorganization in clinical populations.

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bioRxiv2020

Macroscale connectome manifold expansion in adolescence

AO_SCPLOWBSTRACTC_SCPLOWAdolescence is a critical time for the continued maturation of brain networks. Here, we assessed structural connectome development in a large longitudinal sample ranging from childhood to young adulthood. By projecting high-dimensional connectomes into compact manifold spaces, we identified a marked expansion of structural connectomes with the strongest effects in transmodal regions during adolescence. Findings reflected increased within-module connectivity together with increased segregation, indicating increasing differentiation of higher-order association networks from the rest of the brain. Projection of subcortico-cortical connectivity patterns into these manifolds showed parallel alterations in pathways centered on the caudate and thalamus. Connectome findings were contextualized via spatial transcriptome association analysis, highlighting genes enriched in cortex, thalamus, and striatum. Statistical learning of cortical and subcortical manifold features at baseline and their maturational change predicted measures of intelligence at follow-up. Our findings demonstrate that connectome manifold learning can bridge the conceptual and empirical gaps between macroscale network reconfigurations, microscale processes, and cognitive outcomes in adolescent development. IO_SCPLOWMPACTC_SCPLOWManifold learning of longitudinal brain network data provides novel insights into adolescent structural connectome maturation, and how multiple scales of cortical and subcortical organization interact in typical neurodevelopment.

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bioRxiv2020

The cortical wiring scheme of hierarchical information processing

AO_SCPLOWBSTRACTC_SCPLOWThe vast net of fibres within and underneath the cortex is optimised to support the convergence of different levels of brain organisation. Here we propose a novel coordinate system of the human cortex based on an advanced model of its connectivity. Our approach is inspired by seminal, but so far largely neglected models of cortico-cortical wiring established by post mortem anatomical studies and capitalizes on cutting-edge neuroimaging and machine learning. The new model expands the currently prevailing diffusion MRI tractography approach by incorporation of additional features of cortical microstructure and cortico-cortical proximity. Studying several datasets, we could show that our coordinate system robustly recapitulates established sensory-limbic and anterior-posterior dimensions of brain organisation. A series of validation experiments showed that the new wiring space reflects cortical microcircuit features (including pyramidal neuron depth and glial expression) and allowed for competitive simulations of functional connectivity and dynamics across a broad range contexts (based on resting-state fMRI, task-based fMRI, and human intracranial EEG coherence). Our results advance our understanding of how cell-specific neurobiological gradients produce a hierarchical cortical wiring scheme that is concordant with increasing functional sophistication of human brain organisation. Our evaluations demonstrate the cortical wiring space bridges across scales of neural organisation and can be easily translated to single individuals. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=148 SRC="FIGDIR/small/899583v4_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@1b1c601org.highwire.dtl.DTLVardef@3e76c7org.highwire.dtl.DTLVardef@e828e5org.highwire.dtl.DTLVardef@1d4f8ce_HPS_FORMAT_FIGEXP M_FIG C_FIG

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bioRxiv2019

Myeloarchitecture gradients in the human insula serve as blueprints for its diverse connectivity and function

AO_SCPLOWBSTRACTC_SCPLOWInsular cortex is a core hub involved in multiple cognitive and socio-affective processes. Yet, the anatomical mechanisms that explain how it is involved in such a diverse array of functions remain incompletely understood. Here, we define a novel framework to test the hypothesis that changes in myeloarchitecture across the insular cortex explain how it can be involved in many different facets of cognitive function. Detailed intracortical profiling, performed across hundreds of insular locations on the basis of myelin-sensitive magnetic resonance imaging (MRI), was compressed into a lower-dimensional space uncovering principal axes of myeloarchitectonic variation. Leveraging two datasets with different high-resolution MRI contrasts, we obtained robust support for two principal dimensions of insular myeloarchitectonic differentiation in vivo, one running from ventral anterior to posterior banks and one radiating from dorsal anterior towards both ventral anterior and posterior subregions. Analyses of post mortem 3D histological data showed that the antero-posterior axis was mirrored in cytoarchitectural markers, even when controlling for anatomical landmarks and sulco-gyral folding. Resting-state functional connectomics in the same individuals and ad hoc meta-analyses showed that myelin gradients in the insula constrained affiliation to macroscale intrinsic functional systems, showing differential shifts in functional network embedding across each myelin-derived gradient. Collectively, our findings offer a novel approach to capture structure-function interactions of a key node of the limbic system, and suggest a multidimensional structural basis underlying the diverse functional roles of the insula.

neuroscience↗

bioRxiv2019

Functional connectome contractions in temporal lobe epilepsy

AO_SCPLOWBSTRACTC_SCPLOWTemporal lobe epilepsy (TLE) is the most common drug-resistant epilepsy in adults. While commonly related to hippocampal pathology, increasing evidence suggests structural changes beyond the mesiotemporal lobe. Functional anomalies and their link to underlying structural alterations, however, remain incompletely understood. We studied 30 drug-resistant TLE patients and 57 healthy controls using multimodal magnetic resonance imaging analyses. We developed a novel framework that parameterizes functional connectivity distance, consolidating functional and geometric properties of macroscale networks. Compared to controls, TLE showed connectivity distance reductions in temporo-insular and prefrontal networks, suggesting topological segregation of functional networks. Our novel approach furthermore allowed for the testing of morphological and microstructural associations, and revealed that functional connectivity contractions occurred independently from TLE-related cortical atrophy but were mediated by microstructural changes in the underlying white matter. All patients underwent a comparable resective surgery after our study and a regularized supervised machine learning paradigm with 5-fold cross-validation demonstrated that patient-specific functional anomalies predicted post-surgical seizure outcome with 74{+/-}8% accuracy, outperforming classifiers operating on clinical and structural imaging features. Our findings suggest connectivity distance contractions as a clinically relevant pathoconnectomic substrate of TLE. Functional topological isolation may represent a microstructurally mediated network mechanism that tilts the balance towards epileptogenesis.

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bioRxiv2019

BrainSpace: a toolbox for the analysis of macroscale gradients in neuroimaging and connectomics datasets

Understanding how higher order cognitive function emerges from the underlying brain structure depends on quantifying how the behaviour of discrete regions are integrated within the broader cortical landscape. Recent work has established that this macroscale brain organization and function can be quantified in a compact manner through the use of multivariate machine learning approaches that identify manifolds often described as cortical gradients. By quantifying topographic principles of macroscale organization, cortical gradients lend an analytical framework to study structural and functional brain organization across species, throughout development and aging, and its perturbations in disease. More generally, its macroscale perspective on brain organization offers novel possibilities to investigate the complex relationships between brain structure, function, and cognition in a quantified manner. Here, we present a compact workflow and open-access toolbox that allows for (i) the identification of gradients (from structural or functional imaging data), (ii) their alignment (across subjects or modalities), and (iii) their visualization (in embedding or cortical space). Our toolbox also allows for controlled association studies between gradients with other brain-level features, adjusted with respect to several null models that account for spatial autocorrelation. The toolbox is implemented in both Python and Matlab, programming languages widely used by the neuroimaging and network neuroscience communities. Several use-case examples and validation experiments demonstrate the usage and consistency of our tools for the analysis of functional and microstructural gradients across different spatial scales.

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bioRxiv2019

Targeting age-related differences in brain and cognition with multimodal imaging and connectome topography profiling

I.AO_SCPLOWBSTRACTC_SCPLOWAging is characterised by accumulation of structural and metabolic changes in the brain. Recent studies suggest transmodal brain networks are especially sensitive to aging, which, we hypothesise, may be due to their apical position in the cortical hierarchy. Studying an open-access healthy cohort (n=102, age range = 30-89 years) with MRI and A{beta} PET data, we estimated age-related cortical thinning, hippocampal atrophy and A{beta} deposition. In addition to carrying out surface-based morphological and metabolic mapping, we stratified effects along neocortical and hippocampal resting-state functional connectome gradients derived from independent datasets. The cortical gradient depicts an axis of functional differentiation from sensory-motor regions to transmodal regions, whereas the hippocampal gradient recapitulates its long-axis. While age-related thinning and increased A{beta} deposition occurred across the entire cortical topography, increased A{beta} deposition was especially pronounced towards higher-order transmodal regions. Age-related atrophy was greater towards the posterior end of the hippocampal long-axis. No significant effect of age on A{beta} deposition in the hippocampus was observed. Imaging markers correlated with behavioural measures of fluid intelligence and episodic memory in a topography-specific manner. Our results strengthen existing evidence of structural and metabolic change in the aging brain and support the use of connectivity gradients as a compact framework to analyse and conceptualize brain-based biomarkers of aging.

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bioRxiv2019

A molecular gradient along the longitudinal axis of the human hippocampus informs large-scale behavioral systems

The functional organization of the hippocampus is distributed as a gradient along its longitudinal axis that explains its differential interaction with diverse brain systems. We show that the location of human tissue samples extracted along the longitudinal axis of the hippocampus can be predicted within 2mm using the expression pattern of less than 100 genes. When variation in this specific gene expression pattern was observed across the whole brain, a distinct anterioventral-posteriodorsal gradient was observed. Frontal, anterior temporal and brainstem regions involved in social and motivational behaviors, selectively vulnerable to frontotemporal dementia and more functionally connected to the anterior hippocampus could be clearly differentiated from posterior parieto-occipital and cerebellar regions involved in spatial cognition, selectively vulnerable to Alzheimers disease, and more functionally connected to the posterior hippocampus. These findings place the human hippocampus at the interface of two major brain systems defined by a single distinct molecular gradient. (148/150)

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bioRxiv2018

Dissociations between microstructural and functional hierarchies within regions of transmodal cortex

While the role of cortical microstructure in organising neural function is well established, it remains unclear how structural constraints can give rise to more flexible elements of cognition. While non-human primate research has demonstrated a close structure-function correspondence, the relationship between microstructure and function remains poorly understood in humans, in part because of the reliance on post mortem analyses which cannot be directly related to functional data. To overcome this barrier, we developed a novel approach to model the similarity of microstructural profiles sampled in the direction of cortical columns. Our approach was initially formulated based on an ultra-high-resolution 3D histological reconstruction of an entire human brain and then translated to myelin-sensitive MRI data in a large cohort of healthy adults. This novel method identified a system-level gradient of microstructural differentiation traversing from primary sensory to limbic regions that followed shifts in laminar differentiation and cytoarchitectural complexity. Importantly, while microstructural and functional gradients described a similar hierarchy, they became increasingly dissociated in transmodal default mode and fronto-parietal networks. Meta analytic decoding of these topographic dissociations highlighted involvement in higher-level aspects of cognition such as cognitive control and social cognition. Our findings demonstrate a relative decoupling of macroscale functional from microstructural gradients in transmodal regions, which likely contributes to the flexible role these regions play in human cognition.

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