192 research outputs found
Comparative quantitative analysis reveals preserved structural connectivity patterns in the human and macaque brain
The macaque brain serves as a model for the human brain, but its suitability is challenged by unique human features, including connectivity reconfigurations, which emerged during primate evolution. We perform a quantitative comparative analysis of the whole brain macroscale structural connectivity of the two species. Our findings suggest that the human and macaque brain as a whole are similarly wired. A region-wise analysis reveals many interspecies similarities of connectivity patterns, but also lack thereof, primarily involving cingulate and parietal regions. We unravel a common structural backbone in both species involving a highly overlapping set of regions. This structural backbone, important for mediating information across the brain, constitutes a feature of the primate brain persevering evolution. Our findings illustrate novel evolutionary aspects at the macroscale connectivity level, including the existence of common topological structures, and offer a quantitative translational bridge between macaque and human research
Comparative Connectomics.
We introduce comparative connectomics, the quantitative study of cross-species commonalities and variations in brain network topology that aims to discover general principles of network architecture of nervous systems and the identification of species-specific features of brain connectivity. By comparing connectomes derived from simple to more advanced species, we identify two conserved themes of wiring: the tendency to organize network topology into communities that serve specialized functionality and the general drive to enable high topological integration by means of investment of neural resources in short communication paths, hubs, and rich clubs. Within the space of wiring possibilities that conform to these common principles, we argue that differences in connectome organization between closely related species support adaptations in cognition and behavior.We thank Lianne Scholtens, Jim Rilling, Tom Schoenemann for discussions and comments. MPvdH was supported by a VENI (# 451-12-001) grant from the Netherlands Organization for Scientific Research (NWO) and a Fellowship of MQ.This is the author accepted manuscript. The final version is available from Elsevier via https://doi.org/10.1016/j.tics.2016.03.00
Building connectomes using diffusion MRI: why, how and but
Why has diffusion MRI become a principal modality for mapping connectomes in vivo? How do different image acquisition parameters, fiber tracking algorithms and other methodological choices affect connectome estimation? What are the main factors that dictate the success and failure of connectome reconstruction? These are some of the key questions that we aim to address in this review. We provide an overview of the key methods that can be used to estimate the nodes and edges of macroscale connectomes, and we discuss open problems and inherent limitations. We argue that diffusion MRI-based connectome mapping methods are still in their infancy and caution against blind application of deep white matter tractography due to the challenges inherent to connectome reconstruction. We review a number of studies that provide evidence of useful microstructural and network properties that can be extracted in various independent and biologically-relevant contexts. Finally, we highlight some of the key deficiencies of current macroscale connectome mapping methodologies and motivate future developments
The role of symmetry in neural networks and their Laplacian spectra
Human and animal nervous systems constitute complexly wired networks that form the infrastructure for neural processing and integration of information. The organization of these neural networks can be analyzed using the so-called Laplacian spectrum, providing a mathematical tool to produce systems-level network fingerprints. In this article, we examine a characteristic central peak in the spectrum of neural networks, including anatomical brain network maps of the mouse, cat and macaque, as well as anatomical and functional network maps of human brain connectivity. We link the occurrence of this central peak to the level of symmetry in neural networks, an intriguing aspect of network organization resulting from network elements that exhibit similar wiring patterns. Specifically, we propose a measure to capture the global level of symmetry of a network and show that, for both empirical networks and network models, the height of the main peak in the Laplacian spectrum is strongly related to node symmetry in the underlying network. Moreover, examination of spectra of duplication-based model networks shows that neural spectra are best approximated using a trade-off between duplication and diversification. Taken together, our results facilitate a better understanding of neural network spectra and the importance of symmetry in neural networks
Heritability and cross-species comparisons of human cortical functional organization asymmetry
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, that is 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 functional trajectory from perceptual/action to abstract cognition. Whereas language network showed leftward asymmetric organization, frontoparietal network showed rightward asymmetric organization in humans. These asymmetries were heritable in humans and showed a similar spatial distribution with macaques, in the case of intra-hemispheric asymmetry of functional hierarchy. This suggests (phylo)genetic conservation. However, both language and frontoparietal networks showed a qualitatively larger asymmetry in humans relative to macaques. Overall, our findings suggest a genetic basis for asymmetry in intrinsic functional organization, linked to higher order cognitive functions uniquely developed in humans
Estimating the impact of structural directionality: How reliable are undirected connectomes?
Directionality is a fundamental feature of network connections. Most
structural brain networks are intrinsically directed because of the nature of
chemical synapses, which comprise most neuronal connections. Due to limitations
of non-invasive imaging techniques, the directionality of connections between
structurally connected regions of the human brain cannot be confirmed. Hence,
connections are represented as undirected, and it is still unknown how this
lack of directionality affects brain network topology. Using six directed brain
networks from different species and parcellations (cat, mouse, C. elegans, and
three macaque networks), we estimate the inaccuracies in network measures
(degree, betweenness, clustering coefficient, path length, global efficiency,
participation index, and small worldness) associated with the removal of the
directionality of connections. We employ three different methods to render
directed brain networks undirected: (i) remove uni-directional connections,
(ii) add reciprocal connections, and (iii) combine equal numbers of removed and
added uni-directional connections. We quantify the extent of inaccuracy in
network measures introduced through neglecting connection directionality for
individual nodes and across the network. We find that the coarse division
between core and peripheral nodes remains accurate for undirected networks.
However, hub nodes differ considerably when directionality is neglected.
Comparing the different methods to generate undirected networks from directed
ones, we generally find that the addition of reciprocal connections (false
positives) causes larger errors in graph-theoretic measures than the removal of
the same number of directed connections (false negatives). These findings
suggest that directionality plays an essential role in shaping brain networks
and highlight some limitations of undirected connectomes.Comment: 29 pages, 6 figures, 9 supplementary figures, 4 supplementary table
Dwelling Quietly in the Rich Club: Brain Network Determinants of Slow Cortical Fluctuations
For more than a century, cerebral cartography has been driven by
investigations of structural and morphological properties of the brain across
spatial scales and the temporal/functional phenomena that emerge from these
underlying features. The next era of brain mapping will be driven by studies
that consider both of these components of brain organization simultaneously --
elucidating their interactions and dependencies. Using this guiding principle,
we explored the origin of slowly fluctuating patterns of synchronization within
the topological core of brain regions known as the rich club, implicated in the
regulation of mood and introspection. We find that a constellation of densely
interconnected regions that constitute the rich club (including the anterior
insula, amygdala, and precuneus) play a central role in promoting a stable,
dynamical core of spontaneous activity in the primate cortex. The slow time
scales are well matched to the regulation of internal visceral states,
corresponding to the somatic correlates of mood and anxiety. In contrast, the
topology of the surrounding "feeder" cortical regions show unstable, rapidly
fluctuating dynamics likely crucial for fast perceptual processes. We discuss
these findings in relation to psychiatric disorders and the future of
connectomics.Comment: 35 pages, 6 figure
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Morphogenetic Principles of Brain Organisation in Health and Disease
Non-invasive neuroimaging methods, such as MRI, provide a window into the structure of the mammalian brain. However, despite the ubiquity of these methods, the biological interpretation of the information obtained using these tools remains elusive. In order to accurately link this macroscale data to microscale measurements, it is critical that the construct validity is high. This thesis provides novel analyses, pipelines and methods to: i) generate and validate maps of brain organisation obtained via MRI, and ii) demonstrate the utility of these methods in capturing elements of cognition and psychopathology.
First, in Chapter 1, I review some of the neuroscientific context for the new methods presented, from cytoarchitecture to gene expression to connectomes. Chapters 2-4 introduce a new method, âMorphometric Similarity Mappingâ, which captures the brain organisation of an individual by mapping the relationships of multiple features of the cerebral cortex. Chapter 2 focuses on the development of the analysis pipeline and the graph theoretical features of the resulting morphometric similarity networks (MSNs), with an emphasis on reproducibility. Chapter 3 highlights the generalisability of MSNs to the macaque monkey, linking MSNs to ex vivo tract tracing experiments and presenting new tools for processing non-human imaging data; as well as evidence that MSN topography is organised by cytoarchitectonic features. Chapter 4 is focused on determining the transcriptomic correlates of MSNs using publicly available gene expression maps, and on applying MSNs to examine the relationship between brain organisation and intelligence.
Chapter 5 is dedicated to rigorous evaluation of the applicability of MSNs to measure specific disease-relevant phenotypes in 8 rare genetic disorder cohorts. This includes the validation of novel methods for utilising data from both single-cell sequencing technologies and differential gene expression experiments (in multiple tissue types) in analysing neuroimaging and bulk transcriptomic brain maps.
Chapter 6 provides a brief summary and presents some ongoing and future projects expanding on this original work. It also importantly discusses a general framework of comparing brain maps, including MSNs and gene expression, as well as other canonical maps of brain structure and function.
Altogether, this thesis presents and evaluates novel methods and applications for integrating multimodal neuroimaging data with genetic data derived from multiple tissue types and through various acquisition strategies. It also includes tools for performing these analyses in non-human primates, and pipelines for statistically comparing brain maps. These results not only provide insight into the manifestation of brain-related changes due to various components of human variation, but also provides a framework for evaluating this variation at multiple biological scales purely from non-invasive neuroimaging data
Dynamic reconfiguration of macaque brain networks during natural vision
Natural vision engages a wide range of higher-level regions that integrate visual information over the large-scale brain network. How interareal connectivity reconfigures during the processing of ongoing natural visual scenes and how these dynamic functional changes relate to the underlaying anatomical links between regions is not well understood. Here, we hypothesized that macaque visual brain regions are poly-functional sharing the capacity to change their configuration state depending on the nature of visual input. To address this hypothesis, we reconstructed networks from in-vivo diffusion-weighted imaging (DWI) and functional magnetic resonance imaging (fMRI) data obtained in four alert macaque monkeys viewing naturalistic movie scenes. At first, we characterized network properties and found greater interhemispheric density and greater inter-subject variability in free-viewing networks as compared to structural networks. From the structural connectivity, we then captured modules on which we identified hubs during free-viewing that formed a widespread visuo-saccadic network across frontal (FEF, 46v), parietal (LIP, Tpt), and occipitotemporal modules (MT, V4, TEm), and that excluded primary visual cortex. Inter-subject variability of well-connected hubs reflected subject-specific configurations that largely recruited occipito-parietal and frontal modules. Across the cerebral hemispheres, free-viewing networks showed higher correlations among long-distance brain regions as compared to structural networks. From these findings, we hypothesized that long-distance interareal connectivity could reconfigure depending on the ongoing changes in visual scenes. Testing this hypothesis by applying temporally resolved functional connectivity we observed that many structurally defined areas (such as areas V4, MT/MST and LIP) were poly-functional as they were recruited as hub members of multiple network states that changed during the presentation of scenes containing objects, motion, faces, and actions. We suggest that functional flexibility in macaque macroscale brain networks is required for the efficient interareal communication during active natural vision. To further promote the use of naturalistic free-viewing paradigms and increase the development of macaque neuroimaging resources, we share our datasets in the PRIME-DE consortium
Fundamental activity constraints lead to specific interpretations of the connectome
The continuous integration of experimental data into coherent models of the
brain is an increasing challenge of modern neuroscience. Such models provide a
bridge between structure and activity, and identify the mechanisms giving rise
to experimental observations. Nevertheless, structurally realistic network
models of spiking neurons are necessarily underconstrained even if experimental
data on brain connectivity are incorporated to the best of our knowledge.
Guided by physiological observations, any model must therefore explore the
parameter ranges within the uncertainty of the data. Based on simulation
results alone, however, the mechanisms underlying stable and physiologically
realistic activity often remain obscure. We here employ a mean-field reduction
of the dynamics, which allows us to include activity constraints into the
process of model construction. We shape the phase space of a multi-scale
network model of the vision-related areas of macaque cortex by systematically
refining its connectivity. Fundamental constraints on the activity, i.e.,
prohibiting quiescence and requiring global stability, prove sufficient to
obtain realistic layer- and area-specific activity. Only small adaptations of
the structure are required, showing that the network operates close to an
instability. The procedure identifies components of the network critical to its
collective dynamics and creates hypotheses for structural data and future
experiments. The method can be applied to networks involving any neuron model
with a known gain function.Comment: J. Schuecker and M. Schmidt contributed equally to this wor
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