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      Small-World Brain Networks Revisited

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          Abstract

          It is nearly 20 years since the concept of a small-world network was first quantitatively defined, by a combination of high clustering and short path length; and about 10 years since this metric of complex network topology began to be widely applied to analysis of neuroimaging and other neuroscience data as part of the rapid growth of the new field of connectomics. Here, we review briefly the foundational concepts of graph theoretical estimation and generation of small-world networks. We take stock of some of the key developments in the field in the past decade and we consider in some detail the implications of recent studies using high-resolution tract-tracing methods to map the anatomical networks of the macaque and the mouse. In doing so, we draw attention to the important methodological distinction between topological analysis of binary or unweighted graphs, which have provided a popular but simple approach to brain network analysis in the past, and the topology of weighted graphs, which retain more biologically relevant information and are more appropriate to the increasingly sophisticated data on brain connectivity emerging from contemporary tract-tracing and other imaging studies. We conclude by highlighting some possible future trends in the further development of weighted small-worldness as part of a deeper and broader understanding of the topology and the functional value of the strong and weak links between areas of mammalian cortex.

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          A mesoscale connectome of the mouse brain.

          Comprehensive knowledge of the brain's wiring diagram is fundamental for understanding how the nervous system processes information at both local and global scales. However, with the singular exception of the C. elegans microscale connectome, there are no complete connectivity data sets in other species. Here we report a brain-wide, cellular-level, mesoscale connectome for the mouse. The Allen Mouse Brain Connectivity Atlas uses enhanced green fluorescent protein (EGFP)-expressing adeno-associated viral vectors to trace axonal projections from defined regions and cell types, and high-throughput serial two-photon tomography to image the EGFP-labelled axons throughout the brain. This systematic and standardized approach allows spatial registration of individual experiments into a common three dimensional (3D) reference space, resulting in a whole-brain connectivity matrix. A computational model yields insights into connectional strength distribution, symmetry and other network properties. Virtual tractography illustrates 3D topography among interconnected regions. Cortico-thalamic pathway analysis demonstrates segregation and integration of parallel pathways. The Allen Mouse Brain Connectivity Atlas is a freely available, foundational resource for structural and functional investigations into the neural circuits that support behavioural and cognitive processes in health and disease.
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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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              Small-world brain networks.

              Many complex networks have a small-world topology characterized by dense local clustering or cliquishness of connections between neighboring nodes yet a short path length between any (distant) pair of nodes due to the existence of relatively few long-range connections. This is an attractive model for the organization of brain anatomical and functional networks because a small-world topology can support both segregated/specialized and distributed/integrated information processing. Moreover, small-world networks are economical, tending to minimize wiring costs while supporting high dynamical complexity. The authors introduce some of the key mathematical concepts in graph theory required for small-world analysis and review how these methods have been applied to quantification of cortical connectivity matrices derived from anatomical tract-tracing studies in the macaque monkey and the cat. The evolution of small-world networks is discussed in terms of a selection pressure to deliver cost-effective information-processing systems. The authors illustrate how these techniques and concepts are increasingly being applied to the analysis of human brain functional networks derived from electroencephalography/magnetoencephalography and fMRI experiments. Finally, the authors consider the relevance of small-world models for understanding the emergence of complex behaviors and the resilience of brain systems to pathological attack by disease or aberrant development. They conclude that small-world models provide a powerful and versatile approach to understanding the structure and function of human brain systems.
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                Author and article information

                Journal
                Neuroscientist
                Neuroscientist
                NRO
                spnro
                The Neuroscientist
                SAGE Publications (Sage CA: Los Angeles, CA )
                1073-8584
                1089-4098
                21 September 2016
                October 2017
                : 23
                : 5
                : 499-516
                Affiliations
                [1 ]Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA
                [2 ]Department of Electrical and Systems Engineering, University of Pennsylvania, Philadelphia, PA, USA
                [3 ]Department of Psychiatry, University of Cambridge, Cambridge, UK
                [4 ]ImmunoPsychiatry, Immuno-Inflammation Therapeutic Area Unit, GlaxoSmithKline R&D, Stevenage, UK
                Author notes
                [*]Danielle S. Bassett, Department of Bioengineering, University of Pennsylvania, 210 S. 33rd Street, 240 Skirkanich Hall, Philadelphia, PA, 19104, USA. Email: dsb@ 123456seas.upenn.edu
                Article
                10.1177_1073858416667720
                10.1177/1073858416667720
                5603984
                27655008
                882a45bb-f299-4d5b-a2a2-804000a27caa
                © The Author(s) 2016

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 34.0 License ( http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                Funding
                Funded by: Division of Behavioral and Cognitive Sciences, FundRef https://doi.org/10.13039/100000169;
                Award ID: BCS-1441502
                Funded by: Directorate for Mathematical and Physical Sciences, FundRef https://doi.org/10.13039/100000086;
                Award ID: PHY-1554488
                Funded by: National Institute of Mental Health, FundRef https://doi.org/10.13039/100000025;
                Award ID: 2-R01-DC-009209-11
                Funded by: National Institute of Child Health and Human Development, FundRef https://doi.org/10.13039/100000071;
                Award ID: 1R01HD086888-01
                Categories
                Reviews

                graph theory,small-world network,network neuroscience,connectomics,small-world propensity

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