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      Can sliding-window correlations reveal dynamic functional connectivity in resting-state fMRI?

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          Abstract

          During the last several years, the focus of research on resting-state functional magnetic resonance imaging (fMRI) has shifted from the analysis of functional connectivity averaged over the duration of scanning sessions to the analysis of changes of functional connectivity within sessions. Although several studies have reported the presence of dynamic functional connectivity (dFC), statistical assessment of the results is not always carried out in a sound way and, in some studies, is even omitted. In this study, we explain why appropriate statistical tests are needed to detect dFC, we describe how they can be carried out and how to assess the performance of dFC measures, and we illustrate the methodology using spontaneous blood-oxygen level-dependent (BOLD) fMRI recordings of macaque monkeys under general anesthesia and in human subjects under resting-state conditions. We mainly focus on sliding-window correlations since these are most widely used in assessing dFC, but also consider a recently proposed non-linear measure. The simulations and methodology, however, are general and can be applied to any measure. The results are twofold. First, through simulations, we show that in typical resting-state sessions of 10 min, it is almost impossible to detect dFC using sliding-window correlations. This prediction is validated by both the macaque and the human data: in none of the individual recording sessions was evidence for dFC found. Second, detection power can be considerably increased by session- or subject-averaging of the measures. In doing so, we found that most of the functional connections are in fact dynamic. With this study, we hope to raise awareness of the statistical pitfalls in the assessment of dFC and how they can be avoided by using appropriate statistical methods.

          Highlights

          • Not widely recognized is the need for proper statistical testing to assess dynamic functional connectivity in resting-state fMRI.

          • This study describes how to test and how not to test for dynamic functional connectivity.

          • Large-scale dynamic functional networks are found in macaque monkeys under anesthesia.

          • Dynamic functional networks comprise both cortical and sub-cortical regions.

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          Most cited references32

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          Resting-state networks show dynamic functional connectivity in awake humans and anesthetized macaques.

          Characterization of large-scale brain networks using blood-oxygenation-level-dependent functional magnetic resonance imaging is typically based on the assumption of network stationarity across the duration of scan. Recent studies in humans have questioned this assumption by showing that within-network functional connectivity fluctuates on the order of seconds to minutes. Time-varying profiles of resting-state networks (RSNs) may relate to spontaneously shifting, electrophysiological network states and are thus mechanistically of particular importance. However, because these studies acquired data from awake subjects, the fluctuating connectivity could reflect various forms of conscious brain processing such as passive mind wandering, active monitoring, memory formation, or changes in attention and arousal during image acquisition. Here, we characterize RSN dynamics of anesthetized macaques that control for these accounts, and compare them to awake human subjects. We find that functional connectivity among nodes comprising the "oculomotor (OCM) network" strongly fluctuated over time during awake as well as anaesthetized states. For time dependent analysis with short windows (<60 s), periods of positive functional correlations alternated with prominent anticorrelations that were missed when assessed with longer time windows. Similarly, the analysis identified network nodes that transiently link to the OCM network and did not emerge in average RSN analysis. Furthermore, time-dependent analysis reliably revealed transient states of large-scale synchronization that spanned all seeds. The results illustrate that resting-state functional connectivity is not static and that RSNs can exhibit nonstationary, spontaneous relationships irrespective of conscious, cognitive processing. The findings imply that mechanistically important network information can be missed when using average functional connectivity as the single network measure. Copyright © 2012 Wiley Periodicals, Inc., a Wiley company.
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            EEG-correlated fMRI of human alpha activity.

            Electroencephalography-correlated functional magnetic resonance imaging (EEG/fMRI) can be used to identify blood oxygen level-dependent (BOLD) signal changes associated with both physiological and pathological EEG events. Here, we implemented continuous and simultaneous EEG/fMRI to identify BOLD signal changes related to spontaneous power fluctuations in the alpha rhythm (8-12 Hz), the dominant EEG pattern during relaxed wakefulness. Thirty-two channels of EEG were recorded in 10 subjects during eyes-closed rest inside a 1.5-T magnet resonance (MR) scanner using an MR-compatible EEG recording system. Functional scanning by echoplanar imaging covered almost the entire cerebrum every 4 s. Off-line MRI artifact subtraction software was applied to obtain continuous EEG data during fMRI acquisition. The average alpha power over 1-s epochs was derived at several electrode positions using a Fast Fourier Transform. The power time course was then convolved with a canonical hemodynamic response function, down-sampled, and used for statistical parametric mapping of associated signal changes in the image time series. At all electrode positions studied, a strong negative correlation of parietal and frontal cortical activity with alpha power was found. Conversely, only sparse and nonsystematic positive correlation was detected. The relevance of these findings is discussed in view of the current theories on the generation and significance of the alpha rhythm and the related functional neuroimaging findings.
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              Signature of consciousness in the dynamics of resting-state brain activity.

              At rest, the brain is traversed by spontaneous functional connectivity patterns. Two hypotheses have been proposed for their origins: they may reflect a continuous stream of ongoing cognitive processes as well as random fluctuations shaped by a fixed anatomical connectivity matrix. Here we show that both sources contribute to the shaping of resting-state networks, yet with distinct contributions during consciousness and anesthesia. We measured dynamical functional connectivity with functional MRI during the resting state in awake and anesthetized monkeys. Under anesthesia, the more frequent functional connectivity patterns inherit the structure of anatomical connectivity, exhibit fewer small-world properties, and lack negative correlations. Conversely, wakefulness is characterized by the sequential exploration of a richer repertoire of functional configurations, often dissimilar to anatomical structure, and comprising positive and negative correlations among brain regions. These results reconcile theories of consciousness with observations of long-range correlation in the anesthetized brain and show that a rich functional dynamics might constitute a signature of consciousness, with potential clinical implications for the detection of awareness in anesthesia and brain-lesioned patients.
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                Author and article information

                Contributors
                Journal
                Neuroimage
                Neuroimage
                Neuroimage
                Academic Press
                1053-8119
                1095-9572
                15 February 2016
                15 February 2016
                : 127
                : 242-256
                Affiliations
                [a ]Center for Brain and Cognition, Computational Neuroscience Group, Department of Information and Communication Technologies, Universitat Pompeu Fabra, Barcelona, Spain
                [b ]Department of Health Sciences and Technology, ETH Zurich, Switzerland
                [c ]Department of Experimental Psychology, University of Oxford, United Kingdom
                [d ]Department of Physiology of Cognitive Processes, Max Planck Institute for Biological Cybernetics, Tübingen, Germany
                [e ]Instituci Catalana de la Recerca i Estudis Avanats (ICREA), Universitat Pompeu Fabra, Barcelona, Spain
                Author notes
                [* ]Corresponding author at: Center for Brain and Cognition, Computational Neuroscience Group, Department of Information and Communication Technologies, Universitat Pompeu Fabra, Carrer Tanger 122-140, 08018 Barcelona, Spain.Center for Brain and CognitionComputational Neuroscience GroupDepartment of Information and Communication TechnologiesUniversitat Pompeu FabraCarrer Tanger 122-140Barcelona08018Spain rikkert.hindriks@ 123456upf.edu
                Article
                S1053-8119(15)01078-2
                10.1016/j.neuroimage.2015.11.055
                4758830
                26631813
                0792a92d-f200-4169-837d-14285e6db48b
                © 2015 The Authors

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

                History
                : 16 June 2015
                : 23 November 2015
                Categories
                Article

                Neurosciences
                resting state,functional mri,dynamic functional connectivity,surrogate data
                Neurosciences
                resting state, functional mri, dynamic functional connectivity, surrogate data

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