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      Default Mode Network Oscillatory Coupling Is Increased Following Concussion

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          Abstract

          Concussion is a common form of mild traumatic brain injury. Despite the descriptor “mild,” a single injury can leave long-lasting and sustained alterations to brain function, including changes to localized activity and large-scale interregional communication. Cognitive complaints are thought to arise from such functional deficits. We investigated the impact of injury on neurophysiological and functionally specialized resting networks, known as intrinsic connectivity networks (ICNs), using magnetoencephalography. We assessed neurophysiological connectivity in 40 males, 20 with concussion and 20 without. Regions-of-interest that comprise nodes of ICNs were defined, and their time courses derived using a beamformer approach. Pairwise fluctuations and covariations in band-limited amplitude envelopes were computed reflecting measures of functional connectivity. Intra-network connectivity was compared between groups using permutation testing and correlated with symptoms. We observed increased resting spectral connectivity in the default mode network (DMN) and motor networks (MOTs) in our concussion group when compared with controls, across alpha through gamma ranges. Moreover, these differences were not explained by power spectrum density within the ICNs. Furthermore, this increased coupling was significantly associated with symptoms in the DMN and MOTs—but once accounting for comorbidities (including, depression, anxiety, and ADHD) only the DMN continued to be associated with symptoms. The DMN plays a critical role in shifting between cognitive tasks. These data suggest even a single concussion can perturb the intrinsic coupling of this functionally specialized network in the brain, and may explain persistent and wide-ranging symptomatology.

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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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            Investigating the electrophysiological basis of resting state networks using magnetoencephalography.

            In recent years the study of resting state brain networks (RSNs) has become an important area of neuroimaging. The majority of studies have used functional magnetic resonance imaging (fMRI) to measure temporal correlation between blood-oxygenation-level-dependent (BOLD) signals from different brain areas. However, BOLD is an indirect measure related to hemodynamics, and the electrophysiological basis of connectivity between spatially separate network nodes cannot be comprehensively assessed using this technique. In this paper we describe a means to characterize resting state brain networks independently using magnetoencephalography (MEG), a neuroimaging modality that bypasses the hemodynamic response and measures the magnetic fields associated with electrophysiological brain activity. The MEG data are analyzed using a unique combination of beamformer spatial filtering and independent component analysis (ICA) and require no prior assumptions about the spatial locations or patterns of the networks. This method results in RSNs with significant similarity in their spatial structure compared with RSNs derived independently using fMRI. This outcome confirms the neural basis of hemodynamic networks and demonstrates the potential of MEG as a tool for understanding the mechanisms that underlie RSNs and the nature of connectivity that binds network nodes.
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              Graph theoretical analysis of magnetoencephalographic functional connectivity in Alzheimer's disease.

              In this study we examined changes in the large-scale structure of resting-state brain networks in patients with Alzheimer's disease compared with non-demented controls, using concepts from graph theory. Magneto-encephalograms (MEG) were recorded in 18 Alzheimer's disease patients and 18 non-demented control subjects in a no-task, eyes-closed condition. For the main frequency bands, synchronization between all pairs of MEG channels was assessed using a phase lag index (PLI, a synchronization measure insensitive to volume conduction). PLI-weighted connectivity networks were calculated, and characterized by a mean clustering coefficient and path length. Alzheimer's disease patients showed a decrease of mean PLI in the lower alpha and beta band. In the lower alpha band, the clustering coefficient and path length were both decreased in Alzheimer's disease patients. Network changes in the lower alpha band were better explained by a 'Targeted Attack' model than by a 'Random Failure' model. Thus, Alzheimer's disease patients display a loss of resting-state functional connectivity in lower alpha and beta bands even when a measure insensitive to volume conduction effects is used. Moreover, the large-scale structure of lower alpha band functional networks in Alzheimer's disease is more random. The modelling results suggest that highly connected neural network 'hubs' may be especially at risk in Alzheimer's disease.
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                Author and article information

                Contributors
                Journal
                Front Neurol
                Front Neurol
                Front. Neurol.
                Frontiers in Neurology
                Frontiers Media S.A.
                1664-2295
                26 April 2018
                2018
                : 9
                : 280
                Affiliations
                [1] 1Department of Diagnostic Imaging, The Hospital for Sick Children , Toronto, ON, Canada
                [2] 2Neurosciences & Mental Health Program, Sick Kids Research Institute , Toronto, ON, Canada
                [3] 3Department of Medical Imaging, University of Toronto , Toronto, ON, Canada
                [4] 4Holland-Bloorview Kids Rehabilitation Hospital , Toronto, ON, Canada
                [5] 5Division of Neurosurgery, Sunnybrook Hospital , Toronto, ON, Canada
                [6] 6Division of Neurology, The Hospital for Sick Children , Toronto, ON, Canada
                [7] 7Department of Psychology, University of Toronto , Toronto, ON, Canada
                Author notes

                Edited by: Marco Sarà, San Raffaele Cassino, Italy

                Reviewed by: Sergio Bagnato, Fondazione Istituto G. Giglio di Cefalù, Italy; Alexander Fingelkurts, BM-Science, Finland

                *Correspondence: Benjamin T. Dunkley, ben.dunkley@ 123456sickkids.ca

                Specialty section: This article was submitted to Neurotrauma, a section of the journal Frontiers in Neurology

                Article
                10.3389/fneur.2018.00280
                5932404
                e421a5fc-71da-42e9-a360-dd0533b26f1a
                Copyright © 2018 Dunkley, Urban, Da Costa, Wong, Pang and Taylor.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 19 December 2017
                : 09 April 2018
                Page count
                Figures: 4, Tables: 2, Equations: 0, References: 94, Pages: 11, Words: 8052
                Funding
                Funded by: Defence Research and Development Canada 10.13039/501100002956
                Award ID: W7719-135182/001/TOR
                Funded by: Canadian Forces Health Services
                Categories
                Neuroscience
                Original Research

                Neurology
                concussion,mild traumatic brain injury,magnetoencephalography,resting-state,functional connectivity,neural oscillations,synchrony

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