Tracking whole-brain connectivity dynamics in the resting state.

Spontaneous fluctuations are a hallmark of recordings of neural signals, emergent over time scales spanning milliseconds and tens of minutes. However, investigations of intrinsic brain organization based on resting-state functional magnetic resonance imaging have largely not taken into account the presence and potential of temporal variability, as most current approaches to examine functional connectivity (FC) implicitly assume that relationships are constant throughout the length of the recording. In this work, we describe an approach to assess whole-brain FC dynamics based on spatial independent component analysis, sliding time window correlation, and k-means clustering of windowed correlation matrices. The method is applied to resting-state data from a large sample (n = 405) of young adults. Our analysis of FC variability highlights particularly flexible connections between regions in lateral parietal and cingulate cortex, and argues against a labeling scheme where such regions are treated as separate and antagonistic entities. Additionally, clustering analysis reveals unanticipated FC states that in part diverge strongly from stationary connectivity patterns and challenge current descriptions of interactions between large-scale networks. Temporal trends in the occurrence of different FC states motivate theories regarding their functional roles and relationships with vigilance/arousal. Overall, we suggest that the study of time-varying aspects of FC can unveil flexibility in the functional coordination between different neural systems, and that the exploitation of these dynamics in further investigations may improve our understanding of behavioral shifts and adaptive processes.

[1]  Maarten A. S. Boksem,et al.  Cortisol-Induced Increases of Plasma Oxytocin Levels Predict Decreased Immediate Free Recall of Unpleasant Words , 2012, Front. Psychiatry.

[2]  David T. Jones,et al.  Non-Stationarity in the “Resting Brain’s” Modular Architecture , 2012, PloS one.

[3]  Tülay Adali,et al.  Comparison of multi‐subject ICA methods for analysis of fMRI data , 2010, Human brain mapping.

[4]  Stephen M Smith,et al.  Correspondence of the brain's functional architecture during activation and rest , 2009, Proceedings of the National Academy of Sciences.

[5]  L. Pessoa,et al.  Network Analysis Reveals Increased Integration during Emotional and Motivational Processing , 2012, The Journal of Neuroscience.

[6]  V. Haughton,et al.  Mapping functionally related regions of brain with functional connectivity MR imaging. , 2000, AJNR. American journal of neuroradiology.

[7]  Leslie S. Prichep,et al.  Machinery of the Mind , 1990 .

[8]  Theiler,et al.  Generating surrogate data for time series with several simultaneously measured variables. , 1994, Physical review letters.

[9]  Justin L. Vincent,et al.  Evidence for a frontoparietal control system revealed by intrinsic functional connectivity. , 2008, Journal of neurophysiology.

[10]  Charu C. Aggarwal,et al.  On the Surprising Behavior of Distance Metrics in High Dimensional Spaces , 2001, ICDT.

[11]  Jean-Baptiste Poline,et al.  Brain covariance selection: better individual functional connectivity models using population prior , 2010, NIPS.

[12]  Edward T. Bullmore,et al.  Connectomic Intermediate Phenotypes for Psychiatric Disorders , 2012, Front. Psychiatry.

[13]  Steen Moeller,et al.  Multiband multislice GE‐EPI at 7 tesla, with 16‐fold acceleration using partial parallel imaging with application to high spatial and temporal whole‐brain fMRI , 2010, Magnetic resonance in medicine.

[14]  Marc Joliot,et al.  The resting state questionnaire: An introspective questionnaire for evaluation of inner experience during the conscious resting state , 2010, Brain Research Bulletin.

[15]  Mark W. Woolrich,et al.  Network modelling methods for FMRI , 2011, NeuroImage.

[16]  B. Biswal,et al.  Functional connectivity in the motor cortex of resting human brain using echo‐planar mri , 1995, Magnetic resonance in medicine.

[17]  T. Koenig,et al.  Brain electric microstates and momentary conscious mind states as building blocks of spontaneous thinking: I. Visual imagery and abstract thoughts. , 1998, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

[18]  Carl D. Meyer,et al.  Matrix Analysis and Applied Linear Algebra , 2000 .

[19]  M. Czisch,et al.  Development of the brain's default mode network from wakefulness to slow wave sleep. , 2011, Cerebral cortex.

[20]  G L Shulman,et al.  INAUGURAL ARTICLE by a Recently Elected Academy Member:A default mode of brain function , 2001 .

[21]  Manuel S. Schröter,et al.  Development of a Large-Scale Functional Brain Network during Human Non-Rapid Eye Movement Sleep , 2010, The Journal of Neuroscience.

[22]  Justin L. Vincent,et al.  Precuneus shares intrinsic functional architecture in humans and monkeys , 2009, Proceedings of the National Academy of Sciences.

[23]  Ravi S. Menon,et al.  Resting‐state networks show dynamic functional connectivity in awake humans and anesthetized macaques , 2013, Human brain mapping.

[24]  A. Kleinschmidt,et al.  Distributed and Antagonistic Contributions of Ongoing Activity Fluctuations to Auditory Stimulus Detection , 2009, The Journal of Neuroscience.

[25]  Karl J. Friston,et al.  Cerebral Cortex doi:10.1093/cercor/bhr050 Ongoing Brain Activity Fluctuations Directly Account for Intertrial and Indirectly for Intersubject Variability in Stroop Task Performance , 2011 .

[26]  Vince D. Calhoun,et al.  SimTB, a simulation toolbox for fMRI data under a model of spatiotemporal separability , 2012, NeuroImage.

[27]  Justin L. Vincent,et al.  Spontaneous neuronal activity distinguishes human dorsal and ventral attention systems. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[28]  Darren Price,et al.  Investigating the electrophysiological basis of resting state networks using magnetoencephalography , 2011, Proceedings of the National Academy of Sciences.

[29]  M. Boly,et al.  Baseline brain activity fluctuations predict somatosensory perception in humans , 2007, Proceedings of the National Academy of Sciences.

[30]  Catie Chang,et al.  3225 Dynamics of resting-state functional connectivity associated with heart rate variability , 2011 .

[31]  Martin A. Lindquist,et al.  Dynamic connectivity regression: Determining state-related changes in brain connectivity , 2012, NeuroImage.

[32]  Vince D. Calhoun,et al.  Capturing inter-subject variability with group independent component analysis of fMRI data: A simulation study , 2012, NeuroImage.

[33]  Sam T. Roweis,et al.  EM Algorithms for PCA and SPCA , 1997, NIPS.

[34]  A. Grinvald,et al.  Dynamics of Ongoing Activity: Explanation of the Large Variability in Evoked Cortical Responses , 1996, Science.

[35]  R. Tibshirani,et al.  Sparse inverse covariance estimation with the graphical lasso. , 2008, Biostatistics.

[36]  Jeffrey M. Zacks,et al.  Coherent spontaneous activity accounts for trial-to-trial variability in human evoked brain responses , 2006, Nature Neuroscience.

[37]  Tracy Warbrick,et al.  Spontaneous brain activity and EEG microstates. A novel EEG/fMRI analysis approach to explore resting-state networks , 2010, NeuroImage.

[38]  P. Matthews,et al.  Distinct patterns of brain activity in young carriers of the APOE e4 allele , 2009, NeuroImage.

[39]  Abraham Z. Snyder,et al.  Spurious but systematic correlations in functional connectivity MRI networks arise from subject motion , 2012, NeuroImage.

[40]  Terrence J. Sejnowski,et al.  An Information-Maximization Approach to Blind Separation and Blind Deconvolution , 1995, Neural Computation.

[41]  Vince D. Calhoun,et al.  A method for functional network connectivity among spatially independent resting-state components in schizophrenia , 2008, NeuroImage.

[42]  V. Haughton,et al.  Frequencies contributing to functional connectivity in the cerebral cortex in "resting-state" data. , 2001, AJNR. American journal of neuroradiology.

[43]  M. Corbetta,et al.  Temporal dynamics of spontaneous MEG activity in brain networks , 2010, Proceedings of the National Academy of Sciences.

[44]  Jonathan D. Power,et al.  Modulation of the brain's functional network architecture in the transition from wake to sleep. , 2011, Progress in brain research.

[45]  Yufeng Zang,et al.  Spontaneous Brain Activity in the Default Mode Network Is Sensitive to Different Resting-State Conditions with Limited Cognitive Load , 2009, PloS one.

[46]  R Cameron Craddock,et al.  A whole brain fMRI atlas generated via spatially constrained spectral clustering , 2012, Human brain mapping.

[47]  J. Pekar,et al.  A method for making group inferences from functional MRI data using independent component analysis , 2001, Human brain mapping.

[48]  J. Hennig,et al.  Three‐dimensional MR‐encephalography: Fast volumetric brain imaging using rosette trajectories , 2011, Magnetic resonance in medicine.

[49]  M. Raichle,et al.  Resting states affect spontaneous BOLD oscillations in sensory and paralimbic cortex. , 2008, Journal of neurophysiology.

[50]  D. Schacter,et al.  The Brain's Default Network , 2008, Annals of the New York Academy of Sciences.

[51]  M. Corbetta,et al.  Control of goal-directed and stimulus-driven attention in the brain , 2002, Nature Reviews Neuroscience.

[52]  Kent A. Kiehl,et al.  A method for evaluating dynamic functional network connectivity and task-modulation: application to schizophrenia , 2010, Magnetic Resonance Materials in Physics, Biology and Medicine.

[53]  S. P. Lloyd,et al.  Least squares quantization in PCM , 1982, IEEE Trans. Inf. Theory.

[54]  D. Lehmann,et al.  Segmentation of brain electrical activity into microstates: model estimation and validation , 1995, IEEE Transactions on Biomedical Engineering.

[55]  Bharat B. Biswal,et al.  Competition between functional brain networks mediates behavioral variability , 2008, NeuroImage.

[56]  Catie Chang,et al.  Time–frequency dynamics of resting-state brain connectivity measured with fMRI , 2010, NeuroImage.

[57]  Kenneth Hugdahl,et al.  Prediction of human errors by maladaptive changes in event-related brain networks , 2008, Proceedings of the National Academy of Sciences.

[58]  P. Roelfsema,et al.  Slow brain oscillations of sleep, resting state, and vigilance. , 2011, Progress in brain research.

[59]  Olaf Sporns,et al.  Weight-conserving characterization of complex functional brain networks , 2011, NeuroImage.

[60]  O. Tervonen,et al.  The effect of model order selection in group PICA , 2010, Human brain mapping.

[61]  Han Yuan,et al.  Spatiotemporal dynamics of the brain at rest — Exploring EEG microstates as electrophysiological signatures of BOLD resting state networks , 2012, NeuroImage.

[62]  Walter Schneider,et al.  Identifying the brain's most globally connected regions , 2010, NeuroImage.

[63]  O. Tervonen,et al.  Correction of low-frequency physiological noise from the resting state BOLD fMRI—Effect on ICA default mode analysis at 1.5T , 2010, Journal of Neuroscience Methods.

[64]  Hillary D. Schwarb,et al.  Short‐time windows of correlation between large‐scale functional brain networks predict vigilance intraindividually and interindividually , 2013, Human brain mapping.

[65]  P. Bandettini,et al.  The effect of respiration variations on independent component analysis results of resting state functional connectivity , 2008, Human brain mapping.

[66]  G. Glover,et al.  Dissociable Intrinsic Connectivity Networks for Salience Processing and Executive Control , 2007, The Journal of Neuroscience.

[67]  O. Sporns,et al.  Network centrality in the human functional connectome. , 2012, Cerebral cortex.

[68]  Scott T. Grafton,et al.  Dynamic reconfiguration of human brain networks during learning , 2010, Proceedings of the National Academy of Sciences.

[69]  Vince D. Calhoun,et al.  Decomposing the brain: components and modes, networks and nodes , 2012, Trends in Cognitive Sciences.

[70]  Maurizio Corbetta,et al.  The human brain is intrinsically organized into dynamic, anticorrelated functional networks. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[71]  M. Greicius,et al.  Decoding subject-driven cognitive states with whole-brain connectivity patterns. , 2012, Cerebral cortex.

[72]  O. Sporns,et al.  Mapping the Structural Core of Human Cerebral Cortex , 2008, PLoS biology.

[73]  B. Harrison,et al.  Modulation of Brain Resting-State Networks by Sad Mood Induction , 2008, PloS one.

[74]  Dimitri Van De Ville,et al.  Decoding brain states from fMRI connectivity graphs , 2011, NeuroImage.

[75]  Bernard Mazoyer,et al.  Patterns of hemodynamic low-frequency oscillations in the brain are modulated by the nature of free thought during rest , 2012, NeuroImage.

[76]  V. Calhoun,et al.  Modulation of temporally coherent brain networks estimated using ICA at rest and during cognitive tasks , 2008, Human brain mapping.

[77]  Stephen M. Smith,et al.  Temporally-independent functional modes of spontaneous brain activity , 2012, Proceedings of the National Academy of Sciences.

[78]  C. J. Honeya,et al.  Predicting human resting-state functional connectivity from structural connectivity , 2009 .

[79]  Vesa Kiviniemi,et al.  A Sliding Time-Window ICA Reveals Spatial Variability of the Default Mode Network in Time , 2011, Brain Connect..

[80]  O. Tervonen,et al.  Functional segmentation of the brain cortex using high model order group-PICA. , 2009, NeuroImage.

[81]  Dimitri Van De Ville,et al.  BOLD correlates of EEG topography reveal rapid resting-state network dynamics , 2010, NeuroImage.

[82]  Keith A. Johnson,et al.  Cortical Hubs Revealed by Intrinsic Functional Connectivity: Mapping, Assessment of Stability, and Relation to Alzheimer's Disease , 2009, The Journal of Neuroscience.

[83]  Daniella J. Furman,et al.  Default-Mode and Task-Positive Network Activity in Major Depressive Disorder: Implications for Adaptive and Maladaptive Rumination , 2011, Biological Psychiatry.

[84]  A. Engel,et al.  Single-trial EEG–fMRI reveals the dynamics of cognitive function , 2006, Trends in Cognitive Sciences.

[85]  Juliane Britz,et al.  EEG microstate sequences in healthy humans at rest reveal scale-free dynamics , 2010, Proceedings of the National Academy of Sciences.

[86]  Vince D. Calhoun,et al.  Reactivity of hemodynamic responses and functional connectivity to different states of alpha synchrony: A concurrent EEG-fMRI study , 2010, NeuroImage.

[87]  Rex E. Jung,et al.  A Baseline for the Multivariate Comparison of Resting-State Networks , 2011, Front. Syst. Neurosci..

[88]  S. Makeig,et al.  Imaging human EEG dynamics using independent component analysis , 2006, Neuroscience & Biobehavioral Reviews.

[89]  Dietrich Lehmann,et al.  Brain Electric Microstates and Cognition: The Atoms of Thought , 1990 .

[90]  S. Makeig,et al.  Mining event-related brain dynamics , 2004, Trends in Cognitive Sciences.

[91]  G. Deco,et al.  Emerging concepts for the dynamical organization of resting-state activity in the brain , 2010, Nature Reviews Neuroscience.