Tracking brain arousal fluctuations with fMRI

Significance Changes in vigilance and arousal levels can interfere with the study of brain function with functional MRI (fMRI). However, the difficulty of tracking and modeling arousal state during fMRI typically precludes the assessment of arousal-dependent influences on fMRI measurements. Here, we present evidence that continuous variations in arousal level may be monitored from fMRI data alone and validate this approach with a combination of fMRI, intracortical electrophysiology, and a behavioral measure of arousal. We describe a spatial pattern whose time-varying expression in the fMRI data is found to track both electrophysiological and behavioral arousal fluctuations. These findings have implications for increasing the sensitivity of fMRI as a cognitive and clinical biomarker. Changes in brain activity accompanying shifts in vigilance and arousal can interfere with the study of other intrinsic and task-evoked characteristics of brain function. However, the difficulty of tracking and modeling the arousal state during functional MRI (fMRI) typically precludes the assessment of arousal-dependent influences on fMRI signals. Here we combine fMRI, electrophysiology, and the monitoring of eyelid behavior to demonstrate an approach for tracking continuous variations in arousal level from fMRI data. We first characterize the spatial distribution of fMRI signal fluctuations that track a measure of behavioral arousal; taking this pattern as a template, and using the local field potential as a simultaneous and independent measure of cortical activity, we observe that the time-varying expression level of this template in fMRI data provides a close approximation of electrophysiological arousal. We discuss the potential benefit of these findings for increasing the sensitivity of fMRI as a cognitive and clinical biomarker.

[1]  J. Gaillard,et al.  The EEG of the sleep onset period in insomnia: A discriminant analysis , 1992, Physiology & Behavior.

[2]  R. Ogilvie The process of falling asleep. , 2001, Sleep medicine reviews.

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

[4]  Tetsuya Matsuda,et al.  Influence of arousal level for functional magnetic resonance imaging (fMRI) study: Simultaneous recording of fMRI and electroencephalogram , 2002, Psychiatry and clinical neurosciences.

[5]  Mark S. Cohen,et al.  Simultaneous EEG and fMRI of the alpha rhythm , 2002, Neuroreport.

[6]  R W Guillery,et al.  The role of the thalamus in the flow of information to the cortex. , 2002, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[7]  Hellmuth Obrig,et al.  Correlates of alpha rhythm in functional magnetic resonance imaging and near infrared spectroscopy , 2003, NeuroImage.

[8]  N. Logothetis,et al.  Anatomical and functional MR imaging in the macaque monkey using a vertical large-bore 7 Tesla setup. , 2004, Magnetic resonance imaging.

[9]  M. Hasselmo,et al.  High acetylcholine levels set circuit dynamics for attention and encoding and low acetylcholine levels set dynamics for consolidation. , 2004, Progress in brain research.

[10]  Abraham Z. Snyder,et al.  Transient BOLD responses at block transitions , 2005, NeuroImage.

[11]  C. Saper,et al.  Hypothalamic regulation of sleep and circadian rhythms , 2005, Nature.

[12]  G. Jackson,et al.  Effect of prior cognitive state on resting state networks measured with functional connectivity , 2005, Human brain mapping.

[13]  G. Tononi,et al.  Breakdown of Cortical Effective Connectivity During Sleep , 2005, Science.

[14]  B. Feige,et al.  Cortical and subcortical correlates of electroencephalographic alpha rhythm modulation. , 2005, Journal of neurophysiology.

[15]  B. Jones,et al.  From waking to sleeping: neuronal and chemical substrates. , 2005, Trends in pharmacological sciences.

[16]  S. Rombouts,et al.  Consistent resting-state networks across healthy subjects , 2006, Proceedings of the National Academy of Sciences.

[17]  Roel H. R. Deckers,et al.  Large-amplitude, spatially correlated fluctuations in BOLD fMRI signals during extended rest and early sleep stages. , 2006, Magnetic resonance imaging.

[18]  B. Oken,et al.  Vigilance, alertness, or sustained attention: physiological basis and measurement , 2006, Clinical Neurophysiology.

[19]  M. Fox,et al.  Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging , 2007, Nature Reviews Neuroscience.

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

[21]  Fernando Henrique Lopes da Silva,et al.  The hemodynamic response of the alpha rhythm: An EEG/fMRI study , 2007, NeuroImage.

[22]  A. Chesson,et al.  The American Academy of Sleep Medicine (AASM) Manual for the Scoring of Sleep and Associated Events: Rules, Terminology and Technical Specifications , 2007 .

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

[24]  N. Logothetis,et al.  Neurophysiology of the BOLD fMRI Signal in Awake Monkeys , 2008, Current Biology.

[25]  B. Jones Modulation of Cortical Activation and Behavioral Arousal by Cholinergic and Orexinergic Systems , 2008, Annals of the New York Academy of Sciences.

[26]  E. L. Robinson,et al.  Sleep architecture in unrestrained rhesus monkeys (Macaca mulatta) synchronized to 24-hour light-dark cycles. , 2008, Sleep.

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

[28]  N. Filippini,et al.  Distinct patterns of brain activity in young carriers of the APOE e4 allele , 2009, NeuroImage.

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

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

[31]  Yong He,et al.  Functional connectivity between the thalamus and visual cortex under eyes closed and eyes open conditions: A resting‐state fMRI study , 2009, Human brain mapping.

[32]  Gregor Leicht,et al.  EEG-vigilance and BOLD effect during simultaneous EEG/fMRI measurement , 2009, NeuroImage.

[33]  A. Kleinschmidt,et al.  Intrinsic Connectivity Networks, Alpha Oscillations, and Tonic Alertness: A Simultaneous Electroencephalography/Functional Magnetic Resonance Imaging Study , 2010, The Journal of Neuroscience.

[34]  Christian Windischberger,et al.  Toward discovery science of human brain function , 2010, Proceedings of the National Academy of Sciences.

[35]  M. Schölvinck,et al.  Neural basis of global resting-state fMRI activity , 2010, Proceedings of the National Academy of Sciences.

[36]  M. Czisch,et al.  Increased sleep pressure reduces resting state functional connectivity , 2010, Magnetic Resonance Materials in Physics, Biology and Medicine.

[37]  Lutz Jäncke,et al.  Large-scale functional brain networks in human non-rapid eye movement sleep: insights from combined electroencephalographic/functional magnetic resonance imaging studies , 2011, Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences.

[38]  Russell A. Poldrack,et al.  Functional imaging of sleep vertex sharp transients , 2011, Clinical Neurophysiology.

[39]  Akinori Ueno,et al.  Detecting deteriorated vigilance using percentage of eyelid closure time during behavioral maintenance of wakefulness tests. , 2011, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

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

[41]  M. Czisch,et al.  On the Need of Objective Vigilance Monitoring: Effects of Sleep Loss on Target Detection and Task-Negative Activity Using Combined EEG/fMRI , 2012, Front. Neur..

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

[43]  A. Oeltermann,et al.  Hippocampal–cortical interaction during periods of subcortical silence , 2012, Nature.

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

[45]  Joseph B. Mandeville,et al.  IRON fMRI measurements of CBV and implications for BOLD signal , 2012, NeuroImage.

[46]  Jeff H. Duyn,et al.  Finding thalamic BOLD correlates to posterior alpha EEG , 2012, NeuroImage.

[47]  Michael W. L. Chee,et al.  Sleep deprivation reduces default mode network connectivity and anti-correlation during rest and task performance , 2012, NeuroImage.

[48]  Jin Fan,et al.  Spontaneous Brain Activity Relates to Autonomic Arousal , 2012, The Journal of Neuroscience.

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

[50]  Fenna M. Krienen,et al.  Opportunities and limitations of intrinsic functional connectivity MRI , 2013, Nature Neuroscience.

[51]  Catie Chang,et al.  Decomposition of spontaneous brain activity into distinct fMRI co-activation patterns , 2013, Front. Syst. Neurosci..

[52]  Mark W. Woolrich,et al.  Resting-state fMRI in the Human Connectome Project , 2013, NeuroImage.

[53]  Thomas T. Liu,et al.  The amplitude of the resting-state fMRI global signal is related to EEG vigilance measures , 2013, NeuroImage.

[54]  Mingzhou Ding,et al.  Coupling between visual alpha oscillations and default mode activity , 2013, NeuroImage.

[55]  Hans-Jochen Heinze,et al.  Association between heart rate variability and fluctuations in resting-state functional connectivity , 2013, NeuroImage.

[56]  Kevin Murphy,et al.  Resting-state fMRI confounds and cleanup , 2013, NeuroImage.

[57]  Jeff H. Duyn,et al.  Sleep and the functional connectome , 2013, NeuroImage.

[58]  Yufeng Zang,et al.  Standardizing the intrinsic brain: Towards robust measurement of inter-individual variation in 1000 functional connectomes , 2013, NeuroImage.

[59]  Xiao Liu,et al.  EEG correlates of time-varying BOLD functional connectivity , 2013, NeuroImage.

[60]  Giovanni Piantoni,et al.  Sleep deprivation leads to a loss of functional connectivity in frontal brain regions , 2014, BMC Neuroscience.

[61]  Bing Chen,et al.  An open science resource for establishing reliability and reproducibility in functional connectomics , 2014, Scientific Data.

[62]  Carrie R. H. Innes,et al.  Losing the struggle to stay awake: Divergent thalamic and cortical activity during microsleeps , 2014, Human brain mapping.

[63]  G. Buzsáki,et al.  Optogenetic activation of septal cholinergic neurons suppresses sharp wave ripples and enhances theta oscillations in the hippocampus , 2014, Proceedings of the National Academy of Sciences.

[64]  Jonathan D. Power,et al.  Studying Brain Organization via Spontaneous fMRI Signal , 2014, Neuron.

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

[66]  Gustavo Deco,et al.  Modeling resting-state functional networks when the cortex falls asleep: local and global changes. , 2014, Cerebral cortex.

[67]  Stephen V. David,et al.  Cortical Membrane Potential Signature of Optimal States for Sensory Signal Detection , 2015, Neuron.

[68]  William D S Killgore,et al.  Daytime sleepiness is associated with altered resting thalamocortical connectivity , 2015, Neuroreport.

[69]  Rafael Malach,et al.  Coupling between pupil fluctuations and resting-state fMRI uncovers a slow build-up of antagonistic responses in the human cortex , 2015, NeuroImage.

[70]  B. T. Thomas Yeo,et al.  Co-activated yet disconnected—Neural correlates of eye closures when trying to stay awake , 2015, NeuroImage.