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      Predicting haemodynamic networks using electrophysiology: The role of non-linear and cross-frequency interactions

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          Abstract

          Understanding the electrophysiological basis of resting state networks (RSNs) in the human brain is a critical step towards elucidating how inter-areal connectivity supports healthy brain function. In recent years, the relationship between RSNs (typically measured using haemodynamic signals) and electrophysiology has been explored using functional Magnetic Resonance Imaging (fMRI) and magnetoencephalography (MEG). Significant progress has been made, with similar spatial structure observable in both modalities. However, there is a pressing need to understand this relationship beyond simple visual similarity of RSN patterns. Here, we introduce a mathematical model to predict fMRI-based RSNs using MEG. Our unique model, based upon a multivariate Taylor series, incorporates both phase and amplitude based MEG connectivity metrics, as well as linear and non-linear interactions within and between neural oscillations measured in multiple frequency bands. We show that including non-linear interactions, multiple frequency bands and cross-frequency terms significantly improves fMRI network prediction. This shows that fMRI connectivity is not only the result of direct electrophysiological connections, but is also driven by the overlap of connectivity profiles between separate regions. Our results indicate that a complete understanding of the electrophysiological basis of RSNs goes beyond simple frequency-specific analysis, and further exploration of non-linear and cross-frequency interactions will shed new light on distributed network connectivity, and its perturbation in pathology.

          Highlights

          • We introduce a mathematical model to predict fMRI-based RSNs using MEG.

          • Our model is based on a multi-variate Taylor series expansion.

          • The electrophysiological basis of RSNs goes beyond frequency-band specific analysis.

          • RSNs result 1) from multiple frequency bands and cross-frequency coupling.

          • RSNs result 2) from direct and shared electrophysiological connectivity.

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          Most cited references32

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          Dynamic predictions: oscillations and synchrony in top-down processing.

          Classical theories of sensory processing view the brain as a passive, stimulus-driven device. By contrast, more recent approaches emphasize the constructive nature of perception, viewing it as an active and highly selective process. Indeed, there is ample evidence that the processing of stimuli is controlled by top-down influences that strongly shape the intrinsic dynamics of thalamocortical networks and constantly create predictions about forthcoming sensory events. We discuss recent experiments indicating that such predictions might be embodied in the temporal structure of both stimulus-evoked and ongoing activity, and that synchronous oscillations are particularly important in this process. Coherence among subthreshold membrane potential fluctuations could be exploited to express selective functional relationships during states of expectancy or attention, and these dynamic patterns could allow the grouping and selection of distributed neuronal responses for further processing.
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            Electrophysiological signatures of resting state networks in the human brain.

            Functional neuroimaging and electrophysiological studies have documented a dynamic baseline of intrinsic (not stimulus- or task-evoked) brain activity during resting wakefulness. This baseline is characterized by slow (<0.1 Hz) fluctuations of functional imaging signals that are topographically organized in discrete brain networks, and by much faster (1-80 Hz) electrical oscillations. To investigate the relationship between hemodynamic and electrical oscillations, we have adopted a completely data-driven approach that combines information from simultaneous electroencephalography (EEG) and functional magnetic resonance imaging (fMRI). Using independent component analysis on the fMRI data, we identified six widely distributed resting state networks. The blood oxygenation level-dependent signal fluctuations associated with each network were correlated with the EEG power variations of delta, theta, alpha, beta, and gamma rhythms. Each functional network was characterized by a specific electrophysiological signature that involved the combination of different brain rhythms. Moreover, the joint EEG/fMRI analysis afforded a finer physiological fractionation of brain networks in the resting human brain. This result supports for the first time in humans the coalescence of several brain rhythms within large-scale brain networks as suggested by biophysical studies.
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              Phase lag index: assessment of functional connectivity from multi channel EEG and MEG with diminished bias from common sources.

              To address the problem of volume conduction and active reference electrodes in the assessment of functional connectivity, we propose a novel measure to quantify phase synchronization, the phase lag index (PLI), and compare its performance to the well-known phase coherence (PC), and to the imaginary component of coherency (IC). The PLI is a measure of the asymmetry of the distribution of phase differences between two signals. The performance of PLI, PC, and IC was examined in (i) a model of 64 globally coupled oscillators, (ii) an EEG with an absence seizure, (iii) an EEG data set of 15 Alzheimer patients and 13 control subjects, and (iv) two MEG data sets. PLI and PC were more sensitive than IC to increasing levels of true synchronization in the model. PC and IC were influenced stronger than PLI by spurious correlations because of common sources. All measures detected changes in synchronization during the absence seizure. In contrast to PC, PLI and IC were barely changed by the choice of different montages. PLI and IC were superior to PC in detecting changes in beta band connectivity in AD patients. Finally, PLI and IC revealed a different spatial pattern of functional connectivity in MEG data than PC. The PLI performed at least as well as the PC in detecting true changes in synchronization in model and real data but, at the same token and like-wise the IC, it was much less affected by the influence of common sources and active reference electrodes. Copyright 2007 Wiley-Liss, Inc.
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                Author and article information

                Contributors
                Journal
                Neuroimage
                Neuroimage
                Neuroimage
                Academic Press
                1053-8119
                1095-9572
                15 April 2016
                15 April 2016
                : 130
                : 273-292
                Affiliations
                [a ]Sir Peter Mansfield Magnetic Resonance Centre, School of Physics and Astronomy, University of Nottingham, Nottingham, UK
                [b ]Department of Clinical Neurophysiology and MEG Center, VU University Medical Centre, Amsterdam, The Netherlands
                [c ]Delft University of Technology, Faculty of Electrical Engineering, Mathematics and Computer Science, Delft, The Netherlands
                Author notes
                [* ]Corresponding author at: Sir Peter Mansfield Imaging Centre, School of Physics and Astronomy, University of Nottingham, University Park, Nottingham, UK.Sir Peter Mansfield Imaging CentreSchool of Physics and AstronomyUniversity of NottinghamUniversity ParkNottinghamUK Prejaas.tewarie@ 123456nottingham.ac.uk
                Article
                S1053-8119(16)00068-9
                10.1016/j.neuroimage.2016.01.053
                4819720
                26827811
                831f0bcc-f1d3-45c3-bf3e-4da2a8bb02e2
                © 2016 The Authors. Published by Elsevier Inc.

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

                History
                : 7 October 2015
                : 24 January 2016
                Categories
                Article

                Neurosciences
                magnetoencephalography,meg,functional magnetic resonance imaging,fmri,functional connectivity,resting state network,rsn,relationship between fmri and meg,mapping,multivariate taylor series

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