BOLD signatures of sleep

Sleep can be distinguished from wake by changes in brain electrical activity, typically assessed using electroencephalography (EEG). The hallmark of non-rapid-eye-movement sleep are two major EEG events: slow waves and spindles. Here we sought to identify possible signatures of sleep in brain hemodynamic activity, using simultaneous fMRI-EEG. We found that, during the transition from wake to sleep, blood-oxygen-level-dependent (BOLD) activity evolved from a mixed-frequency pattern to one dominated by two distinct oscillations: a low-frequency (~0.05Hz) oscillation prominent in light sleep and a high-frequency (~0.17Hz) oscillation in deep sleep. The two BOLD oscillations correlated with the occurrences of spindles and slow waves, respectively. They were detectable across the whole brain, cortically and subcortically, but had different regional distributions and opposite onset patterns. These spontaneous BOLD oscillations provide fMRI signatures of basic sleep processes, which may be employed to study human sleep at spatial resolution and brain coverage not achievable using EEG. HIGHLIGHTS spontaneous BOLD oscillations differentiate sleep from wake low-frequency BOLD oscillation tracks sleep spindles high-frequency BOLD oscillation tracks sleep slow waves BOLD oscillations provide fMRI signatures of key sleep processes

[1]  I. Colrain,et al.  Dynamic coupling between the central and autonomic nervous systems during sleep: A review , 2018, Neuroscience & Biobehavioral Reviews.

[2]  G. Tononi,et al.  Human Rapid Eye Movement Sleep Shows Local Increases in Low-Frequency Oscillations and Global Decreases in High-Frequency Oscillations Compared to Resting Wakefulness , 2018, eNeuro.

[3]  Giulio Tononi,et al.  Local and Widespread Slow Waves in Stable NREM Sleep: Evidence for Distinct Regulation Mechanisms , 2018, Front. Hum. Neurosci..

[4]  Bruce R. Rosen,et al.  Ultra-Slow Single-Vessel BOLD and CBV-Based fMRI Spatiotemporal Dynamics and Their Correlation with Neuronal Intracellular Calcium Signals , 2018, Neuron.

[5]  M. Schölvinck,et al.  Subcortical evidence for a contribution of arousal to fMRI studies of brain activity , 2018, Nature Communications.

[6]  Stefan Posse,et al.  On the detection of high frequency correlations in resting state fMRI , 2018, NeuroImage.

[7]  O. Bruni,et al.  Sleep and cortical maturation: slow and fast sleep spindles in the first 4 years of life , 2017 .

[8]  Orrin Devinsky,et al.  Heterogeneous Origins of Human Sleep Spindles in Different Cortical Layers , 2017, The Journal of Neuroscience.

[9]  D. Kleinfeld,et al.  Entrainment of Arteriole Vasomotor Fluctuations by Neural Activity Is a Basis of Blood-Oxygenation-Level-Dependent “Resting-State” Connectivity , 2017, Neuron.

[10]  Maxim Bazhenov,et al.  Coupling of autonomic and central events during sleep benefits declarative memory consolidation , 2019, Neurobiology of Learning and Memory.

[11]  Cornelius Faber,et al.  Cortex-wide BOLD fMRI activity reflects locally-recorded slow oscillation-associated calcium waves , 2017, eLife.

[12]  R. Stickgold,et al.  Characterizing sleep spindles in 11,630 individuals from the National Sleep Research Resource , 2017, Nature Communications.

[13]  Clifford B Saper,et al.  Wake–sleep circuitry: an overview , 2017, Current Opinion in Neurobiology.

[14]  C. Koch,et al.  Are the Neural Correlates of Consciousness in the Front or in the Back of the Cerebral Cortex? Clinical and Neuroimaging Evidence , 2017, The Journal of Neuroscience.

[15]  E. Arrigoni,et al.  Neural Circuitry of Wakefulness and Sleep , 2017, Neuron.

[16]  Sydney S. Cash,et al.  Spatiotemporal characteristics of sleep spindles depend on cortical location , 2017, NeuroImage.

[17]  Joshua J. LaRocque,et al.  The neural correlates of dreaming , 2014, Nature Neuroscience.

[18]  Laura D. Lewis,et al.  Fast fMRI can detect oscillatory neural activity in humans , 2016, Proceedings of the National Academy of Sciences.

[19]  Zhongxing Zhang,et al.  The occurrence of individual slow waves in sleep is predicted by heart rate , 2016, Scientific Reports.

[20]  Jesper Andersson,et al.  A multi-modal parcellation of human cerebral cortex , 2016, Nature.

[21]  S. B. Erdoğan,et al.  Systemic Low-Frequency Oscillations in BOLD Signal Vary with Tissue Type , 2016, Front. Neurosci..

[22]  Daniel Levenstein,et al.  Network Homeostasis and State Dynamics of Neocortical Sleep , 2016, Neuron.

[23]  Catie Chang,et al.  Brain–heart interactions: challenges and opportunities with functional magnetic resonance imaging at ultra-high field , 2016, Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences.

[24]  Plamen Ch Ivanov,et al.  Delay-correlation landscape reveals characteristic time delays of brain rhythms and heart interactions , 2016, Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences.

[25]  Uri Hasson,et al.  Progression to deep sleep is characterized by changes to BOLD dynamics in sensory cortices , 2016, NeuroImage.

[26]  Athena Demertzi,et al.  Propofol-Induced Frontal Cortex Disconnection: A Study of Resting-State Networks, Total Brain Connectivity, and Mean BOLD Signal Oscillation Frequencies , 2016, Brain Connect..

[27]  G. Tononi,et al.  Local Slow Waves in Superficial Layers of Primary Cortical Areas during REM Sleep , 2016, Current Biology.

[28]  S. Daan,et al.  The two‐process model of sleep regulation: a reappraisal , 2016, Journal of sleep research.

[29]  Wolfgang Klimesch,et al.  Heartbeat-related EEG amplitude and phase modulations from wakefulness to deep sleep: Interactions with sleep spindles and slow oscillations. , 2015, Psychophysiology.

[30]  Toru Yanagawa,et al.  Robust Long-Range Coordination of Spontaneous Neural Activity in Waking, Sleep and Anesthesia. , 2015, Cerebral cortex.

[31]  Simon C. Cork,et al.  A Critical Role for Purinergic Signalling in the Mechanisms Underlying Generation of BOLD fMRI Responses , 2015, The Journal of Neuroscience.

[32]  Vincenzo Crunelli,et al.  The thalamocortical network as a single slow wave-generating unit , 2015, Current Opinion in Neurobiology.

[33]  Koenraad Van Leemput,et al.  A computational atlas of the hippocampal formation using ex vivo, ultra-high resolution MRI: Application to adaptive segmentation of in vivo MRI , 2015, NeuroImage.

[34]  Emiliano Ricciardi,et al.  Neural and Behavioral Correlates of Extended Training during Sleep Deprivation in Humans: Evidence for Local, Task-Specific Effects , 2015, The Journal of Neuroscience.

[35]  Gary H. Glover,et al.  BOLD fractional contribution to resting-state functional connectivity above 0.1Hz , 2015, NeuroImage.

[36]  John H. Gilmore,et al.  Frequency of spontaneous BOLD signal shifts during infancy and correlates with cognitive performance , 2014, Developmental Cognitive Neuroscience.

[37]  G. Tononi,et al.  Enhancement of sleep slow waves: underlying mechanisms and practical consequences , 2014, Front. Syst. Neurosci..

[38]  Congwu Du,et al.  Low-frequency calcium oscillations accompany deoxyhemoglobin oscillations in rat somatosensory cortex , 2014, Proceedings of the National Academy of Sciences.

[39]  L. Lemieux,et al.  Electrophysiological correlates of the BOLD signal for EEG‐informed fMRI , 2014, Human brain mapping.

[40]  Wei Gao,et al.  Development of Thalamocortical Connectivity during Infancy and Its Cognitive Correlations , 2014, The Journal of Neuroscience.

[41]  Igor Timofeev,et al.  Global Intracellular Slow-Wave Dynamics of the Thalamocortical System , 2014, The Journal of Neuroscience.

[42]  M. Raichle,et al.  Lag structure in resting-state fMRI. , 2014, Journal of neurophysiology.

[43]  Y. Saalmann Intralaminar and medial thalamic influence on cortical synchrony, information transmission and cognition , 2014, Front. Syst. Neurosci..

[44]  H. Laufs,et al.  Decoding Wakefulness Levels from Typical fMRI Resting-State Data Reveals Reliable Drifts between Wakefulness and Sleep , 2014, Neuron.

[45]  Timothy Edward John Behrens,et al.  Connectivity-based functional analysis of dopamine release in the striatum using diffusion-weighted MRI and positron emission tomography. , 2014, Cerebral cortex.

[46]  C. Tallon-Baudry,et al.  Spontaneous fluctuations in neural responses to heartbeats predict visual detection , 2014, Nature Neuroscience.

[47]  Pietro Perona,et al.  Sleep spindle detection: crowdsourcing and evaluating performance of experts, non-experts, and automated methods , 2014, Nature Methods.

[48]  Matthew B. Bouchard,et al.  Direct, intraoperative observation of ~0.1Hz hemodynamic oscillations in awake human cortex: Implications for fMRI , 2014, NeuroImage.

[49]  Masaki Fukunaga,et al.  Decreased connectivity between the thalamus and the neocortex during human nonrapid eye movement sleep. , 2014, Sleep.

[50]  G. Tononi,et al.  Sleep and the Price of Plasticity: From Synaptic and Cellular Homeostasis to Memory Consolidation and Integration , 2014, Neuron.

[51]  Dieter Jaeger,et al.  Quasi-periodic patterns (QPP): Large-scale dynamics in resting state fMRI that correlate with local infraslow electrical activity , 2014, NeuroImage.

[52]  Jeffrey S. Anderson,et al.  BOLD Granger Causality Reflects Vascular Anatomy , 2013, PloS one.

[53]  Han Yuan,et al.  Correlated slow fluctuations in respiration, EEG, and BOLD fMRI , 2013, NeuroImage.

[54]  Joshua J. LaRocque,et al.  Assessing sleep consciousness within subjects using a serial awakening paradigm , 2013, Front. Psychol..

[55]  A. Braun,et al.  Rhythmic alternating patterns of brain activity distinguish rapid eye movement sleep from other states of consciousness , 2013, Proceedings of the National Academy of Sciences.

[56]  J. Born,et al.  About sleep's role in memory. , 2013, Physiological reviews.

[57]  Christophe Phillips,et al.  The Impact of Visual Perceptual Learning on Sleep and Local Slow-Wave Initiation , 2013, The Journal of Neuroscience.

[58]  H. Critchley,et al.  Visceral Influences on Brain and Behavior , 2013, Neuron.

[59]  Enzo Tagliazucchi,et al.  Automatic sleep staging using fMRI functional connectivity data , 2012, NeuroImage.

[60]  Jeff H. Duyn,et al.  EEG-fMRI Methods for the Study of Brain Networks during Sleep , 2012, Front. Neur..

[61]  Manuel Schabus,et al.  Hierarchical clustering of brain activity during human nonrapid eye movement sleep , 2012, Proceedings of the National Academy of Sciences.

[62]  J. Parvizi,et al.  Functional MRI of sleep spindles and K-complexes , 2012, Clinical Neurophysiology.

[63]  Helmut Laufs,et al.  To wake or not to wake? The two-sided nature of the human K-complex , 2012, NeuroImage.

[64]  Pierre Besson,et al.  MRI atlas of the human hypothalamus , 2012, NeuroImage.

[65]  I. Fried,et al.  Sleep Spindles in Humans: Insights from Intracranial EEG and Unit Recordings , 2011, The Journal of Neuroscience.

[66]  Louise S. Delicato,et al.  Stimulus-induced dissociation of neuronal firing rates and local field potential gamma power and its relationship to the blood oxygen level-dependent signal in macaque primary visual cortex , 2011, The European journal of neuroscience.

[67]  Maxim Volgushev,et al.  Properties of Slow Oscillation during Slow-Wave Sleep and Anesthesia in Cats , 2011, The Journal of Neuroscience.

[68]  J. Born,et al.  Fast and slow spindles during the sleep slow oscillation: disparate coalescence and engagement in memory processing. , 2011, Sleep.

[69]  Richard B. Buxton,et al.  A theoretical framework for estimating cerebral oxygen metabolism changes using the calibrated-BOLD method: Modeling the effects of blood volume distribution, hematocrit, oxygen extraction fraction, and tissue signal properties on the BOLD signal , 2011, NeuroImage.

[70]  Alexis T Baria,et al.  Anatomical and Functional Assemblies of Brain BOLD Oscillations , 2011, The Journal of Neuroscience.

[71]  I. Fried,et al.  Regional Slow Waves and Spindles in Human Sleep , 2011, Neuron.

[72]  G. Tononi,et al.  *Both authors contributed equally to this manuscript. , 2022 .

[73]  Jed A. Meltzer,et al.  Infraslow EEG oscillations organize large-scale cortical–subcortical interactions during sleep: A combined EEG/fMRI study , 2011, Brain Research.

[74]  Peter Achermann,et al.  The sleep EEG as a marker of intellectual ability in school age children. , 2011, Sleep.

[75]  F. Mauguière,et al.  Thalamic deactivation at sleep onset precedes that of the cerebral cortex in humans , 2010, Proceedings of the National Academy of Sciences.

[76]  Gábor Székely,et al.  A mean three-dimensional atlas of the human thalamus: Generation from multiple histological data , 2010, NeuroImage.

[77]  N. Schiff Recovery of consciousness after brain injury: a mesocircuit hypothesis , 2010, Trends in Neurosciences.

[78]  Yevgeniy B. Sirotin,et al.  Spatiotemporal precision and hemodynamic mechanism of optical point spreads in alert primates , 2009, Proceedings of the National Academy of Sciences.

[79]  M. Fukunaga,et al.  Sources of functional magnetic resonance imaging signal fluctuations in the human brain at rest: a 7 T study. , 2009, Magnetic resonance imaging.

[80]  A. Braun,et al.  Decoupling of the brain's default mode network during deep sleep , 2009, Proceedings of the National Academy of Sciences.

[81]  Jörn Diedrichsen,et al.  A probabilistic MR atlas of the human cerebellum , 2009, NeuroImage.

[82]  D. Dijk Regulation and functional correlates of slow wave sleep. , 2009, Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine.

[83]  M. Raichle,et al.  Cortical network functional connectivity in the descent to sleep , 2009, Proceedings of the National Academy of Sciences.

[84]  G. Tononi,et al.  Source modeling sleep slow waves , 2009, Proceedings of the National Academy of Sciences.

[85]  Manuel Schabus,et al.  Spontaneous neural activity during human slow wave sleep , 2008, Proceedings of the National Academy of Sciences.

[86]  Katrin Amunts,et al.  Stereotaxic probabilistic maps of the magnocellular cell groups in human basal forebrain , 2008, NeuroImage.

[87]  M. Fukunaga,et al.  Low frequency BOLD fluctuations during resting wakefulness and light sleep: A simultaneous EEG‐fMRI study , 2008, Human brain mapping.

[88]  Marcello Massimini,et al.  Why Does Consciousness Fade in Early Sleep? , 2008, Annals of the New York Academy of Sciences.

[89]  Masaki Fukunaga,et al.  Metabolic Origin of Bold Signal Fluctuations in the Absence of Stimuli , 2008, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[90]  Marcello Massimini,et al.  Sleep homeostasis and cortical synchronization: III. A high-density EEG study of sleep slow waves in humans. , 2007, Sleep.

[91]  Jeff H. Duyn,et al.  Low-frequency fluctuations in the cardiac rate as a source of variance in the resting-state fMRI BOLD signal , 2007, NeuroImage.

[92]  M. Corbetta,et al.  Electrophysiological signatures of resting state networks in the human brain , 2007, Proceedings of the National Academy of Sciences.

[93]  Manuel Schabus,et al.  Hemodynamic cerebral correlates of sleep spindles during human non-rapid eye movement sleep , 2007, Proceedings of the National Academy of Sciences.

[94]  I. Fried,et al.  Coupling between Neuronal Firing Rate, Gamma LFP, and BOLD fMRI Is Related to Interneuronal Correlations , 2007, Current Biology.

[95]  Helmut Laufs,et al.  'Brain activation and hypothalamic functional connectivity during human non-rapid eye movement sleep: an EEG/fMRI study'--its limitations and an alternative approach. , 2007, Brain : a journal of neurology.

[96]  Marcello Massimini,et al.  Reduced sleep spindle activity in schizophrenia patients , 2007 .

[97]  C. Smith,et al.  Sleep spindles and learning potential. , 2007, Behavioral neuroscience.

[98]  Sean M Montgomery,et al.  Integration and Segregation of Activity in Entorhinal-Hippocampal Subregions by Neocortical Slow Oscillations , 2006, Neuron.

[99]  B. Dan,et al.  A neurophysiological perspective on sleep and its maturation. , 2006, Developmental medicine and child neurology.

[100]  G. Tononi,et al.  Arm immobilization causes cortical plastic changes and locally decreases sleep slow wave activity , 2006, Nature Neuroscience.

[101]  Anders M. Dale,et al.  An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest , 2006, NeuroImage.

[102]  J. Born,et al.  Hippocampal sharp wave-ripples linked to slow oscillations in rat slow-wave sleep. , 2006, Journal of neurophysiology.

[103]  Manuel Schabus,et al.  Sleep spindle‐related activity in the human EEG and its relation to general cognitive and learning abilities , 2006, The European journal of neuroscience.

[104]  Z. Clemens,et al.  Prediction of general mental ability based on neural oscillation measures of sleep , 2005, Journal of sleep research.

[105]  Sean L. Hill,et al.  The Sleep Slow Oscillation as a Traveling Wave , 2004, The Journal of Neuroscience.

[106]  G. Tononi,et al.  Local sleep and learning , 2004, Nature.

[107]  J. Palva,et al.  Infraslow oscillations modulate excitability and interictal epileptic activity in the human cortex during sleep. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[108]  Dae-Shik Kim,et al.  Spatial relationship between neuronal activity and BOLD functional MRI , 2004, NeuroImage.

[109]  Iwao Kanno,et al.  Stimulus frequency dependence of the linear relationship between local cerebral blood flow and field potential evoked by activation of rat somatosensory cortex , 2004, Neuroscience Research.

[110]  M. Ferrara,et al.  Sleep spindles: an overview. , 2003, Sleep medicine reviews.

[111]  K. Uğurbil,et al.  Effect of Basal Conditions on the Magnitude and Dynamics of the Blood Oxygenation Level-Dependent fMRI Response , 2002, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[112]  A. Dale,et al.  Whole Brain Segmentation Automated Labeling of Neuroanatomical Structures in the Human Brain , 2002, Neuron.

[113]  N. Logothetis,et al.  Neurophysiological investigation of the basis of the fMRI signal , 2001, Nature.

[114]  M. Steriade,et al.  Natural waking and sleep states: a view from inside neocortical neurons. , 2001, Journal of neurophysiology.

[115]  A. Villringer,et al.  Spontaneous Low Frequency Oscillations of Cerebral Hemodynamics and Metabolism in Human Adults , 2000, NeuroImage.

[116]  M. Steriade Corticothalamic resonance, states of vigilance and mentation , 2000, Neuroscience.

[117]  Karl J. Friston,et al.  Nonlinear Responses in fMRI: The Balloon Model, Volterra Kernels, and Other Hemodynamics , 2000, NeuroImage.

[118]  M Steriade,et al.  Spiking-bursting activity in the thalamic reticular nucleus initiates sequences of spindle oscillations in thalamic networks. , 2000, Journal of neurophysiology.

[119]  G H Glover,et al.  Image‐based method for retrospective correction of physiological motion effects in fMRI: RETROICOR , 2000, Magnetic resonance in medicine.

[120]  C. Mathiesen,et al.  Temporal coupling between neuronal activity and blood flow in rat cerebellar cortex as indicated by field potential analysis , 2000, The Journal of physiology.

[121]  I. Feinberg,et al.  A Comparison of Period Amplitude Analysis and FFT Power Spectral Analysis of All-Night Human Sleep EEG , 1999, Physiology & Behavior.

[122]  A. Morel,et al.  Multiarchitectonic and stereotactic atlas of the human thalamus , 1997, The Journal of comparative neurology.

[123]  P. Anderer,et al.  Topographic distribution of sleep spindles in young healthy subjects , 1997, Journal of sleep research.

[124]  P. Achermann,et al.  Low-frequency (<1Hz) oscillations in the human sleep electroencephalogram , 1997, Neuroscience.

[125]  P. Achermann,et al.  Fronto‐occipital EEG power gradients in human sleep , 1997, Journal of sleep research.

[126]  D. Contreras,et al.  Cellular basis of EEG slow rhythms: a study of dynamic corticothalamic relationships , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[127]  P. Achermann,et al.  Period‐amplitude analysis and power spectral analysis: a comparison based on all‐night sleep EEG recordings , 1993, Journal of sleep research.

[128]  M. Steriade,et al.  A novel slow (< 1 Hz) oscillation of neocortical neurons in vivo: depolarizing and hyperpolarizing components , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[129]  M. Steriade,et al.  Slow rhythmic oscillations of EEG slow-wave amplitudes and their relations to midbrain reticular discharge , 1983, Brain Research.

[130]  M. Steriade,et al.  Slow rhythmic rate fluctuations of cat midbrain reticular neurons in synchronized sleep and waking , 1982, Brain Research.

[131]  E. Ornitz,et al.  Evolution of sleep spindles in childhood. , 1975, Electroencephalography and Clinical Neurophysiology.

[132]  E. Wolpert A Manual of Standardized Terminology, Techniques and Scoring System for Sleep Stages of Human Subjects. , 1969 .

[133]  M. Steriade,et al.  Reticular facilitation of responses to acoustic stimuli. , 1962, Electroencephalography and clinical neurophysiology.

[134]  M. Steriade,et al.  UNSPECIFIC SYSTEMS OF INHIBITION AND FACILITATION OF POTENTIALS EVOKED BY INTERMITTENT LIGHT , 1960 .

[135]  M. Deschenes,et al.  The deafferented reticular thalamic nucleus generates spindle rhythmicity. , 1987, Journal of neurophysiology.

[136]  A. Borbély A two process model of sleep regulation. , 1982, Human neurobiology.

[137]  A. Rechtschaffen,et al.  A manual of standardized terminology, technique and scoring system for sleep stages of human subjects , 1968 .

[138]  G. Moruzzi,et al.  Brain stem reticular formation and activation of the EEG. , 1949, Electroencephalography and clinical neurophysiology.