Intracranial high-γ connectivity distinguishes wakefulness from sleep

ABSTRACT Neural synchrony in the &ggr;‐band is considered a fundamental process in cortical computation and communication and it has also been proposed as a crucial correlate of consciousness. However, the latter claim remains inconclusive, mainly due to methodological limitations, such as the spectral constraints of scalp‐level electroencephalographic recordings or volume‐conduction confounds. Here, we circumvented these caveats by comparing &ggr;‐band connectivity between two global states of consciousness via intracranial electroencephalography (iEEG), which provides the most reliable measurements of high‐frequency activity in the human brain. Non‐REM Sleep recordings were compared to passive‐wakefulness recordings of the same duration in three subjects with surgically implanted electrodes. Signals were analyzed through the weighted Phase Lag Index connectivity measure and relevant graph theory metrics. We found that connectivity in the high‐&ggr; range (90–120 Hz), as well as relevant graph theory properties, were higher during wakefulness than during sleep and discriminated between conditions better than any other canonical frequency band. Our results constitute the first report of iEEG differences between wakefulness and sleep in the high‐&ggr; range at both local and distant sites, highlighting the utility of this technique in the search for the neural correlates of global states of consciousness. HighlightsIEEG recordings overcome the methodological limitations of other techniques.IEEG high‐&ggr; connectivity is higher during wakefulness than during sleep.It distinguishes between states better than any other canonical frequency band.Connectivity differences are present at both local and distant sites.

[1]  M. Sigman,et al.  Auditory Feedback Differentially Modulates Behavioral and Neural Markers of Objective and Subjective Performance When Tapping to Your Heartbeat , 2015, Cerebral cortex.

[2]  M. Seeck,et al.  Seizure-like phenomena and propofol: A systematic review , 2002, Neurology.

[3]  J. Gotman,et al.  High-frequency oscillations (HFOs) in clinical epilepsy , 2012, Progress in Neurobiology.

[4]  J. Röschke,et al.  Discrimination of sleep stages: a comparison between spectral and nonlinear EEG measures. , 1996, Electroencephalography and clinical neurophysiology.

[5]  T. Bekinschtein,et al.  Cognitive processing during the transition to sleep. , 2012, Archives italiennes de biologie.

[6]  J. Hohwy The neural correlates of consciousness: New experimental approaches needed? , 2009, Consciousness and Cognition.

[7]  A. El-Baz Multi Modality State-of-the-Art Medical Image Segmentation and Registration Methodologies: Volume 1 , 2016 .

[8]  Yong He,et al.  BrainNet Viewer: A Network Visualization Tool for Human Brain Connectomics , 2013, PloS one.

[9]  G. Buzsáki Rhythms of the brain , 2006 .

[10]  Asif A Ghazanfar,et al.  Multisensory Integration of Looming Signals by Rhesus Monkeys , 2004, Neuron.

[11]  Julián J. González,et al.  Interhemispheric differences in awake and sleep human EEG: a comparison between non-linear and spectral measures , 1999, Neuroscience Letters.

[12]  F. H. Lopes da Silva,et al.  Epileptic Neuronal Networks: Methods of Identification and Clinical Relevance , 2012, Front. Neurol..

[13]  O Sporns,et al.  Predicting human resting-state functional connectivity from structural connectivity , 2009, Proceedings of the National Academy of Sciences.

[14]  R. Oostenveld,et al.  Finding Gamma , 2008, Neuron.

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

[16]  Oscar Herreras,et al.  Local Field Potentials: Myths and Misunderstandings , 2016, Front. Neural Circuits.

[17]  Kristin L. Sainani The Importance of Accounting for Correlated Observations , 2010, PM & R : the journal of injury, function, and rehabilitation.

[18]  J. Palva,et al.  New vistas for α-frequency band oscillations , 2007, Trends in Neurosciences.

[19]  Sabine Kastner,et al.  Human consciousness and its relationship to social neuroscience: A novel hypothesis , 2011, Cognitive neuroscience.

[20]  Robert Oostenveld,et al.  An improved index of phase-synchronization for electrophysiological data in the presence of volume-conduction, noise and sample-size bias , 2011, NeuroImage.

[21]  Matthijs Verhage,et al.  A solution to dependency: using multilevel analysis to accommodate nested data , 2014, Nature Neuroscience.

[22]  W. Pan Akaike's Information Criterion in Generalized Estimating Equations , 2001, Biometrics.

[23]  R. Schmidt,et al.  Cross-Frequency Phase–Phase Coupling between Theta and Gamma Oscillations in the Hippocampus , 2012, The Journal of Neuroscience.

[24]  J. Martinerie,et al.  The brainweb: Phase synchronization and large-scale integration , 2001, Nature Reviews Neuroscience.

[25]  J. Changeux,et al.  Experimental and Theoretical Approaches to Conscious Processing , 2011, Neuron.

[26]  Arnaud Delorme,et al.  EEGLAB: an open source toolbox for analysis of single-trial EEG dynamics including independent component analysis , 2004, Journal of Neuroscience Methods.

[27]  S. Holm A Simple Sequentially Rejective Multiple Test Procedure , 1979 .

[28]  T Kobayashi,et al.  Correlation dimension of the human sleep electroencephalogram , 2000, Psychiatry and clinical neurosciences.

[29]  A. Szűcs,et al.  Interictal Epileptic Spiking during Sleep and Wakefulness in Mesial Temporal Lobe Epilepsy: A Comparative Study of Scalp and Foramen Ovale Electrodes , 2003, Epilepsia.

[30]  Brian Litt,et al.  Human and automated detection of high-frequency oscillations in clinical intracranial EEG recordings , 2007, Clinical Neurophysiology.

[31]  C. Koch,et al.  The origin of extracellular fields and currents — EEG, ECoG, LFP and spikes , 2012, Nature Reviews Neuroscience.

[32]  Jan-Mathijs Schoffelen,et al.  A Tutorial Review of Functional Connectivity Analysis Methods and Their Interpretational Pitfalls , 2016, Front. Syst. Neurosci..

[33]  P. Manganotti,et al.  Coherence and Consciousness: Study of Fronto-Parietal Gamma Synchrony in Patients with Disorders of Consciousness , 2014, Brain Topography.

[34]  Guy B. Williams,et al.  Spectral Signatures of Reorganised Brain Networks in Disorders of Consciousness , 2014, PLoS Comput. Biol..

[35]  Itzhak Fried,et al.  Large-Scale Microelectrode Recordings of High-Frequency Gamma Oscillations in Human Cortex during Sleep , 2010, The Journal of Neuroscience.

[36]  Liberty S. Hamilton,et al.  Intonational speech prosody encoding in the human auditory cortex , 2017, Science.

[37]  Mark D. Holmes,et al.  Intracranial EEG power spectra and phase synchrony during consciousness and unconsciousness , 2009, Consciousness and Cognition.

[38]  Nikolai Axmacher,et al.  Phase-locking within human mediotemporal lobe predicts memory formation , 2008, NeuroImage.

[39]  J. Maunsell,et al.  Different Origins of Gamma Rhythm and High-Gamma Activity in Macaque Visual Cortex , 2011, PLoS biology.

[40]  W. Singer,et al.  Synchronization of Neural Activity across Cortical Areas Correlates with Conscious Perception , 2007, The Journal of Neuroscience.

[41]  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.

[42]  Michael Eickenberg,et al.  Machine learning for neuroimaging with scikit-learn , 2014, Front. Neuroinform..

[43]  Morten Overgaard,et al.  Neural Correlates of Contents and Levels of Consciousness , 2010, Front. Psychology.

[44]  Jerome Engel,et al.  The Emergence of Neurosurgical Approaches to the Treatment of Epilepsy , 2005 .

[45]  E. Niebur,et al.  Neural Correlates of High-Gamma Oscillations (60–200 Hz) in Macaque Local Field Potentials and Their Potential Implications in Electrocorticography , 2008, The Journal of Neuroscience.

[46]  Yul-Wan Sung,et al.  Functional magnetic resonance imaging , 2004, Scholarpedia.

[47]  Arthur W. Toga,et al.  A Probabilistic Atlas of the Human Brain: Theory and Rationale for Its Development The International Consortium for Brain Mapping (ICBM) , 1995, NeuroImage.

[48]  Christopher K. Kovach,et al.  Manifestation of ocular-muscle EMG contamination in human intracranial recordings , 2011, NeuroImage.

[49]  A. Seth,et al.  Consciousness and the Prefrontal Parietal Network: Insights from Attention, Working Memory, and Chunking , 2012, Front. Psychology.

[50]  C. Koch,et al.  Neural correlates of consciousness: progress and problems , 2016, Nature Reviews Neuroscience.

[51]  R. Oostenveld,et al.  Nonparametric statistical testing of EEG- and MEG-data , 2007, Journal of Neuroscience Methods.

[52]  R. O’Brien,et al.  A Caution Regarding Rules of Thumb for Variance Inflation Factors , 2007 .

[53]  G. Smyth,et al.  Statistical Applications in Genetics and Molecular Biology Permutation P -values Should Never Be Zero: Calculating Exact P -values When Permutations Are Randomly Drawn , 2011 .

[54]  K. Takano ON SOLUTION OF , 1983 .

[55]  Michael X Cohen,et al.  Analyzing Neural Time Series Data: Theory and Practice , 2014 .

[56]  Asif A Ghazanfar,et al.  Interactions between the Superior Temporal Sulcus and Auditory Cortex Mediate Dynamic Face/Voice Integration in Rhesus Monkeys , 2008, The Journal of Neuroscience.

[57]  Rajesh P. N. Rao,et al.  Broadband changes in the cortical surface potential track activation of functionally diverse neuronal populations , 2014, NeuroImage.

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

[59]  U. Rajendra Acharya,et al.  Non-linear analysis of EEG signals at various sleep stages , 2005, Comput. Methods Programs Biomed..

[60]  B. Gordon,et al.  Induced electrocorticographic gamma activity during auditory perception , 2001, Clinical Neurophysiology.

[61]  J. Palva,et al.  Functional Roles of Alpha-Band Phase Synchronization in Local and Large-Scale Cortical Networks , 2011, Front. Psychology.

[62]  P. Fries Neuronal gamma-band synchronization as a fundamental process in cortical computation. , 2009, Annual review of neuroscience.

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

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

[65]  Josef Parvizi,et al.  Human hippocampal increases in low-frequency power during associative prediction violations , 2013, Neuropsychologia.

[66]  Arthur Gretton,et al.  Inferring spike trains from local field potentials. , 2008, Journal of neurophysiology.

[67]  S. Muthukumaraswamy High-frequency brain activity and muscle artifacts in MEG/EEG: a review and recommendations , 2013, Front. Hum. Neurosci..

[68]  Milan Sonka,et al.  3D Slicer as an image computing platform for the Quantitative Imaging Network. , 2012, Magnetic resonance imaging.

[69]  R. Desimone,et al.  Modulation of Oscillatory Neuronal Synchronization by Selective Visual Attention , 2001, Science.

[70]  Robert Stickgold,et al.  Gamma EEG dynamics in neocortex and hippocampus during human wakefulness and sleep , 2004, NeuroImage.

[71]  Michel Le Van Quyen,et al.  RIPPLELAB: A Comprehensive Application for the Detection, Analysis and Classification of High Frequency Oscillations in Electroencephalographic Signals , 2016, PloS one.

[72]  Erik Edwards,et al.  Comparison of time-frequency responses and the event-related potential to auditory speech stimuli in human cortex. , 2009, Journal of neurophysiology.

[73]  J. Changeux,et al.  Ongoing Spontaneous Activity Controls Access to Consciousness: A Neuronal Model for Inattentional Blindness , 2005, PLoS biology.

[74]  Christoph M. Michel,et al.  Mapping Epileptic Activity: Sources or Networks for the Clinicians? , 2014, Front. Neurol..

[75]  Xiao-Jing Wang Neurophysiological and computational principles of cortical rhythms in cognition. , 2010, Physiological reviews.

[76]  Michael J. Kahana,et al.  Direct brain recordings fuel advances in cognitive electrophysiology , 2010, Trends in Cognitive Sciences.

[77]  György Buzsáki,et al.  What does gamma coherence tell us about inter-regional neural communication? , 2015, Nature Neuroscience.

[78]  N. Tzourio-Mazoyer,et al.  Automated Anatomical Labeling of Activations in SPM Using a Macroscopic Anatomical Parcellation of the MNI MRI Single-Subject Brain , 2002, NeuroImage.

[79]  Jean Gotman,et al.  Scalp spindles are associated with widespread intracranial activity with unexpectedly low synchrony , 2015, NeuroImage.

[80]  C. Elger,et al.  Human memory formation is accompanied by rhinal–hippocampal coupling and decoupling , 2001, Nature Neuroscience.

[81]  Rick L. Jenison,et al.  Sparse Spectro-Temporal Receptive Fields Based on Multi-Unit and High-Gamma Responses in Human Auditory Cortex , 2015, PloS one.

[82]  Vasileios Kokkinos,et al.  Connectivity Measures in EEG Microstructural Sleep Elements , 2016, Front. Neuroinform..

[83]  S. Dehaene,et al.  Towards a cognitive neuroscience of consciousness: basic evidence and a workspace framework , 2001, Cognition.

[84]  G. Buzsáki,et al.  Mechanisms of gamma oscillations. , 2012, Annual review of neuroscience.

[85]  W. Singer,et al.  Temporal binding and the neural correlates of sensory awareness , 2001, Trends in Cognitive Sciences.

[86]  Olaf Sporns,et al.  Complex network measures of brain connectivity: Uses and interpretations , 2010, NeuroImage.

[87]  O. Sporns,et al.  Complex brain networks: graph theoretical analysis of structural and functional systems , 2009, Nature Reviews Neuroscience.

[88]  Venkatapavani Pallavi Punugu Machine Learning in Neuroimaging , 2017 .

[89]  Ram Adapa,et al.  Brain Connectivity Dissociates Responsiveness from Drug Exposure during Propofol-Induced Transitions of Consciousness , 2016, PLoS Comput. Biol..

[90]  Mitchell Steinschneider,et al.  Spectrotemporal analysis of evoked and induced electroencephalographic responses in primary auditory cortex (A1) of the awake monkey. , 2008, Cerebral cortex.

[91]  C. Koch,et al.  Integrated information theory: from consciousness to its physical substrate , 2016, Nature Reviews Neuroscience.

[92]  Liang Wang,et al.  Parcellation‐dependent small‐world brain functional networks: A resting‐state fMRI study , 2009, Human brain mapping.

[93]  Ney Lemke,et al.  Synchronization and Propagation of Global Sleep Spindles , 2016, PloS one.

[94]  J. Gotman,et al.  Interictal spiking during wakefulness and sleep and the localization of foci in temporal lobe epilepsy , 1991, Neurology.

[95]  Fabricio Baglivo,et al.  Early detection of intentional harm in the human amygdala. , 2016, Brain : a journal of neurology.

[96]  P Kahane,et al.  Intracranial EEG and human brain mapping , 2003, Journal of Physiology-Paris.

[97]  Joanna Kabat,et al.  Focal cortical dysplasia – review , 2012, Polish journal of radiology.

[98]  Dominique Hasboun,et al.  Human Gamma Oscillations during Slow Wave Sleep , 2012, PloS one.

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

[100]  Adriano B. L. Tort,et al.  On cross-frequency phase-phase coupling between theta and gamma oscillations in the hippocampus , 2016, eLife.

[101]  I. Nelken,et al.  Transient Induced Gamma-Band Response in EEG as a Manifestation of Miniature Saccades , 2008, Neuron.

[102]  J. Palva,et al.  New vistas for alpha-frequency band oscillations. , 2007, Trends in neurosciences.

[103]  A. Engel,et al.  Invasive recordings from the human brain: clinical insights and beyond , 2005, Nature Reviews Neuroscience.

[104]  Aric Hagberg,et al.  Exploring Network Structure, Dynamics, and Function using NetworkX , 2008, Proceedings of the Python in Science Conference.

[105]  Martin Luessi,et al.  MNE software for processing MEG and EEG data , 2014, NeuroImage.

[106]  P. F. Meier,et al.  Dimensional complexity and spectral properties of the human sleep EEG , 2003, Clinical Neurophysiology.

[107]  S. Kochen,et al.  Expectation and Attention in Hierarchical Auditory Prediction , 2013, The Journal of Neuroscience.

[108]  François Mauguière,et al.  Human thalamic and cortical activities assessed by dimension of activation and spectral edge frequency during sleep wake cycles. , 2007, Sleep.

[109]  Martin Luessi,et al.  MEG and EEG data analysis with MNE-Python , 2013, Front. Neuroinform..

[110]  C. Koch,et al.  Attention and consciousness: two distinct brain processes , 2007, Trends in Cognitive Sciences.

[111]  T. Bullock,et al.  Temporal fluctuations in coherence of brain waves. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[112]  A. Owen,et al.  Are There Levels of Consciousness? , 2016, Trends in Cognitive Sciences.

[113]  R Core Team,et al.  R: A language and environment for statistical computing. , 2014 .

[114]  J. Ebersole,et al.  The accuracy and reliability of 3D CT/MRI co-registration in planning epilepsy surgery , 2009, Clinical Neurophysiology.

[115]  W. Singer,et al.  Neural Synchrony in Cortical Networks: History, Concept and Current Status , 2009, Front. Integr. Neurosci..

[116]  D. C. Mccarthy,et al.  Hippocampal and neocortical gamma oscillations predict memory formation in humans. , 2006, Cerebral cortex.

[117]  B. Gordon,et al.  Induced electrocorticographic gamma activity during auditory perception. Brazier Award-winning article, 2001. , 2001, Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology.

[118]  J. Changeux,et al.  Opinion TRENDS in Cognitive Sciences Vol.10 No.5 May 2006 Conscious, preconscious, and subliminal processing: a testable taxonomy , 2022 .