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      Network-Level Structure-Function Relationships in Human Neocortex

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          Abstract

          The dynamics of spontaneous fluctuations in neural activity are shaped by underlying patterns of anatomical connectivity. While numerous studies have demonstrated edge-wise correspondence between structural and functional connections, much less is known about how large-scale coherent functional network patterns emerge from the topology of structural networks. In the present study, we deploy a multivariate statistical technique, partial least squares, to investigate the association between spatially extended structural networks and functional networks. We find multiple statistically robust patterns, reflecting reliable combinations of structural and functional subnetworks that are optimally associated with one another. Importantly, these patterns generally do not show a one-to-one correspondence between structural and functional edges, but are instead distributed and heterogeneous, with many functional relationships arising from nonoverlapping sets of anatomical connections. We also find that structural connections between high-degree hubs are disproportionately represented, suggesting that these connections are particularly important in establishing coherent functional networks. Altogether, these results demonstrate that the network organization of the cerebral cortex supports the emergence of diverse functional network configurations that often diverge from the underlying anatomical substrate.

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          Most cited references33

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          Rich-club organization of the human connectome.

          The human brain is a complex network of interlinked regions. Recent studies have demonstrated the existence of a number of highly connected and highly central neocortical hub regions, regions that play a key role in global information integration between different parts of the network. The potential functional importance of these "brain hubs" is underscored by recent studies showing that disturbances of their structural and functional connectivity profile are linked to neuropathology. This study aims to map out both the subcortical and neocortical hubs of the brain and examine their mutual relationship, particularly their structural linkages. Here, we demonstrate that brain hubs form a so-called "rich club," characterized by a tendency for high-degree nodes to be more densely connected among themselves than nodes of a lower degree, providing important information on the higher-level topology of the brain network. Whole-brain structural networks of 21 subjects were reconstructed using diffusion tensor imaging data. Examining the connectivity profile of these networks revealed a group of 12 strongly interconnected bihemispheric hub regions, comprising the precuneus, superior frontal and superior parietal cortex, as well as the subcortical hippocampus, putamen, and thalamus. Importantly, these hub regions were found to be more densely interconnected than would be expected based solely on their degree, together forming a rich club. We discuss the potential functional implications of the rich-club organization of the human connectome, particularly in light of its role in information integration and in conferring robustness to its structural core.
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            Structural and functional brain networks: from connections to cognition.

            How rich functionality emerges from the invariant structural architecture of the brain remains a major mystery in neuroscience. Recent applications of network theory and theoretical neuroscience to large-scale brain networks have started to dissolve this mystery. Network analyses suggest that hierarchical modular brain networks are particularly suited to facilitate local (segregated) neuronal operations and the global integration of segregated functions. Although functional networks are constrained by structural connections, context-sensitive integration during cognition tasks necessarily entails a divergence between structural and functional networks. This degenerate (many-to-one) function-structure mapping is crucial for understanding the nature of brain networks. The emergence of dynamic functional networks from static structural connections calls for a formal (computational) approach to neuronal information processing that may resolve this dialectic between structure and function.
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              The small world of the cerebral cortex.

              While much information is available on the structural connectivity of the cerebral cortex, especially in the primate, the main organizational principles of the connection patterns linking brain areas, columns and individual cells have remained elusive. We attempt to characterize a wide variety of cortical connectivity data sets using a specific set of graph theory methods. We measure global aspects of cortical graphs including the abundance of small structural motifs such as cycles, the degree of local clustering of connections and the average path length. We examine large-scale cortical connection matrices obtained from neuroanatomical data bases, as well as probabilistic connection matrices at the level of small cortical neuronal populations linked by intra-areal and inter-areal connections. All cortical connection matrices examined in this study exhibit "small-world" attributes, characterized by the presence of abundant clustering of connections combined with short average distances between neuronal elements. We discuss the significance of these universal organizational features of cortex in light of functional brain anatomy. Supplementary materials are at www.indiana.edu/~cortex/lab.htm.
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                Author and article information

                Journal
                Cereb Cortex
                Cereb. Cortex
                cercor
                cercor
                Cerebral Cortex (New York, NY)
                Oxford University Press
                1047-3211
                1460-2199
                July 2016
                21 April 2016
                21 April 2016
                : 26
                : 7
                : 3285-3296
                Affiliations
                [1 ]McConnel Brain Imaging Centre, Montreal Neurological Institute, McGill University , Montréal, QC, H3A 2B4, Canada
                [2 ]Department of Psychological and Brain Sciences
                [3 ]Indiana University Network Science Institute, Indiana University , Bloomington, IN, 47405, USA
                [4 ]Department of Bioengineering, University of Pennsylvania , Philadelphia, PA, 19104, USA
                [5 ]Brain Center Rudolf Magnus, UMC Utrecht , Utrecht, 3508 GA, The Netherlands
                [6 ]Department of Psychology, University of Chicago , Chicago, IL, 60637, USA
                [7 ]Rotman Research Institute, Baycrest Centre , Toronto, ON, M6A 2E1, Canada
                Author notes
                Address correspondence to Bratislav Mišić, McConnel Brain Imaging Centre, Montreal Neurological Institute, McGill University, 3801 Rue University, Montréal, QC, H3A 2B4 Canada. Email: bratislav.misic@ 123456mcgill.ca
                Article
                bhw089
                10.1093/cercor/bhw089
                4898678
                27102654
                23b10f22-05b2-44e5-b358-195ea116083d
                © The Author 2016. Published by Oxford University Press

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                Funding
                Funded by: Natural Sciences and Engineering Research Council of Canada Postdoctoral Fellowship
                Funded by: J.S. McDonnell Foundation
                Award ID: 220020387
                Funded by: the National Science Foundation
                Award ID: 1212778
                Funded by: the National Institutes of Health
                Award ID: NIH R01 AT009036-01
                Funded by: the National Science Foundation/Integrative Graduate Education and Research Training Program in the Dynamics of Brain-Body-Environment Systems at Indiana University
                Funded by: Human Connectome Project, WU-Minn Consortium
                Award ID: 1U54MH091657
                Funded by: McDonnell Center for Systems Neuroscience at Washington University
                Categories
                Articles

                Neurology
                connectome,multivariate,network,partial least squares
                Neurology
                connectome, multivariate, network, partial least squares

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