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      The Potential of the Human Connectome as a Biomarker of Brain Disease

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          Abstract

          The human connectome at the level of fiber tracts between brain regions has been shown to differ in patients with brain disorders compared to healthy control groups. Nonetheless, there is a potentially large number of different network organizations for individual patients that could lead to cognitive deficits prohibiting correct diagnosis. Therefore changes that can distinguish groups might not be sufficient to diagnose the disease that an individual patient suffers from and to indicate the best treatment option for that patient. We describe the challenges introduced by the large variability of connectomes within healthy subjects and patients and outline three common strategies to use connectomes as biomarkers of brain diseases. Finally, we propose a fourth option in using models of simulated brain activity (the dynamic connectome) based on structural connectivity rather than the structure (connectome) itself as a biomarker of disease. Dynamic connectomes, in addition to currently used structural, functional, or effective connectivity, could be an important future biomarker for clinical applications.

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          Most cited references18

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          A tension-based theory of morphogenesis and compact wiring in the central nervous system.

          Many structural features of the mammalian central nervous system can be explained by a morphogenetic mechanism that involves mechanical tension along axons, dendrites and glial processes. In the cerebral cortex, for example, tension along axons in the white matter can explain how and why the cortex folds in a characteristic species-specific pattern. In the cerebellum, tension along parallel fibres can explain why the cortex is highly elongated but folded like an accordion. By keeping the aggregate length of axonal and dendritic wiring low, tension should contribute to the compactness of neural circuitry throughout the adult brain.
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            The blue brain project.

            IBM's Blue Gene supercomputer allows a quantum leap in the level of detail at which the brain can be modelled. I argue that the time is right to begin assimilating the wealth of data that has been accumulated over the past century and start building biologically accurate models of the brain from first principles to aid our understanding of brain function and dysfunction.
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              High-cost, high-capacity backbone for global brain communication.

              Network studies of human brain structural connectivity have identified a specific set of brain regions that are both highly connected and highly central. Recent analyses have shown that these putative hub regions are mutually and densely interconnected, forming a "rich club" within the human brain. Here we show that the set of pathways linking rich club regions forms a central high-cost, high-capacity backbone for global brain communication. Diffusion tensor imaging (DTI) data of two sets of 40 healthy subjects were used to map structural brain networks. The contributions to network cost and communication capacity of global cortico-cortical connections were assessed through measures of their topology and spatial embedding. Rich club connections were found to be more costly than predicted by their density alone and accounted for 40% of the total communication cost. Furthermore, 69% of all minimally short paths between node pairs were found to travel through the rich club and a large proportion of these communication paths consisted of ordered sequences of edges ("path motifs") that first fed into, then traversed, and finally exited the rich club, while passing through nodes of increasing and then decreasing degree. The prevalence of short paths that follow such ordered degree sequences suggests that neural communication might take advantage of strategies for dynamic routing of information between brain regions, with an important role for a highly central rich club. Taken together, our results show that rich club connections make an important contribution to interregional signal traffic, forming a central high-cost, high-capacity backbone for global brain communication.
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                Author and article information

                Journal
                2013-10-15
                Article
                10.3389/fnhum.2013.00484
                1310.4010
                5389832a-be13-4a68-86cf-e631b987b5aa

                http://arxiv.org/licenses/nonexclusive-distrib/1.0/

                History
                Custom metadata
                Frontiers in Human Neuroscience 7:484, 2013
                Perspective Article for special issue on Magnetic Resonance Imaging of Healthy and Diseased Brain Networks
                q-bio.NC physics.med-ph

                Medical physics,Neurosciences
                Medical physics, Neurosciences

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