Brain imaging reveals covert consciousness during behavioral unresponsiveness induced by propofol

Detecting covert consciousness in behaviorally unresponsive patients by brain imaging is of great interest, but a reproducible model and evidence from independent sources is still lacking. Here we demonstrate the possibility of using general anesthetics in a within-subjects study design to test methods or statistical paradigms of assessing covert consciousness. Using noninvasive neuroimaging in healthy volunteers, we identified a healthy study participant who was able to exhibit the specific fMRI signatures of volitional mental imagery while behaviorally unresponsive due to sedation with propofol. Our findings reveal a novel model that may accelerate the development of new approaches to reproducibly detect covert consciousness, which is difficult to achieve in patients with heterogeneous and sometimes clinically unstable neuropathology.

[1]  Steven Laureys,et al.  When thoughts become action: An fMRI paradigm to study volitional brain activity in non-communicative brain injured patients , 2007, NeuroImage.

[2]  Jakob Hohwy,et al.  Reforming the taxonomy in disorders of consciousness , 2017, Annals of neurology.

[3]  Quentin Noirhomme,et al.  Reanalysis of “Bedside detection of awareness in the vegetative state: a cohort study” , 2013, The Lancet.

[4]  Walter G Sannita,et al.  Unresponsive wakefulness syndrome: a new name for the vegetative state or apallic syndrome , 2010, BMC medicine.

[5]  J. Binder,et al.  Scale-Free Functional Connectivity of the Brain Is Maintained in Anesthetized Healthy Participants but Not in Patients with Unresponsive Wakefulness Syndrome , 2014, PloS one.

[6]  Scott Peltier,et al.  Attenuated Brain Response to Auditory Word Stimulation with Sevoflurane: A Functional Magnetic Resonance Imaging Study in Humans , 2005, Anesthesiology.

[7]  Ludovico Minati,et al.  Multimodal study of default‐mode network integrity in disorders of consciousness , 2016, Annals of neurology.

[8]  Jun Zhang,et al.  How are different neural networks related to consciousness? , 2015, Annals of neurology.

[9]  Zhong Yang,et al.  Decoupled temporal variability and signal synchronization of spontaneous brain activity in loss of consciousness: An fMRI study in anesthesia , 2016, NeuroImage.

[10]  Paul A. Taylor,et al.  FMRI Clustering in AFNI: False-Positive Rates Redux , 2017, Brain Connect..

[11]  G. Mashour,et al.  Timescales of Intrinsic BOLD Signal Dynamics and Functional Connectivity in Pharmacologic and Neuropathologic States of Unconsciousness , 2018, The Journal of Neuroscience.

[12]  Steven Laureys,et al.  A role for the default mode network in the bases of disorders of consciousness , 2012, Annals of neurology.

[13]  G. McCarthy,et al.  The Impact of NMDA Receptor Blockade on Human Working Memory-Related Prefrontal Function and Connectivity , 2013, Neuropsychopharmacology.

[14]  Hans Knutsson,et al.  Cluster failure: Why fMRI inferences for spatial extent have inflated false-positive rates , 2016, Proceedings of the National Academy of Sciences.

[15]  A. Hudetz,et al.  Differential Effects of Deep Sedation with Propofol on the Specific and Nonspecific Thalamocortical Systems: A Functional Magnetic Resonance Imaging Study , 2013, Anesthesiology.

[16]  Matthew H. Davis,et al.  Residual auditory function in persistent vegetative state: a combined pet and fmri study , 2005, Neuropsychological rehabilitation.

[17]  Jamie Sleigh,et al.  Incidence of Connected Consciousness after Tracheal Intubation: A Prospective, International, Multicenter Cohort Study of the Isolated Forearm Technique , 2017, Anesthesiology.

[18]  R. Clauss,et al.  Extraordinary arousal from semi-comatose state on zolpidem. A case report. , 2000, South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde.

[19]  A. Owen,et al.  The dissociation between command following and communication in disorders of consciousness: an fMRI study in healthy subjects , 2015, Front. Hum. Neurosci..

[20]  Lionel Naccache,et al.  Is She Conscious? , 2006, Science.

[21]  Takahiro Suzuki,et al.  Changes in Cerebral Blood Flow and Oxygenation During Induction of General Anesthesia with Sevoflurane Versus Propofol. , 2016, Advances in experimental medicine and biology.

[22]  Mark Hallett,et al.  Modulating Conscious Movement Intention by Noninvasive Brain Stimulation and the Underlying Neural Mechanisms , 2015, The Journal of Neuroscience.

[23]  Mary M. Conte,et al.  Characterization of EEG signals revealing covert cognition in the injured brain , 2018, Brain : a journal of neurology.

[24]  N. Morton,et al.  Pharmacokinetic model driven infusion of propofol in children. , 1991, British journal of anaesthesia.

[25]  M. Boly,et al.  Breakdown of within- and between-network Resting State Functional Magnetic Resonance Imaging Connectivity during Propofol-induced Loss of Consciousness , 2010, Anesthesiology.

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

[27]  Emery N Brown,et al.  Controversy in statistical analysis of functional magnetic resonance imaging data , 2017, Proceedings of the National Academy of Sciences.

[28]  Biyu J. He,et al.  Volition and Action in the Human Brain: Processes, Pathologies, and Reasons , 2017, The Journal of Neuroscience.

[29]  M. Bruno,et al.  Quantitative rates of brain glucose metabolism distinguish minimally conscious from vegetative state patients , 2014, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[30]  Ray Johnson,et al.  Information Loss over Time Defines the Memory Defect of Propofol: A Comparative Response with Thiopental and Dexmedetomidine , 2004, Anesthesiology.

[31]  Matthew H. Davis,et al.  Dissociating speech perception and comprehension at reduced levels of awareness , 2007, Proceedings of the National Academy of Sciences.

[32]  George A. Mashour,et al.  Prevention of Intraoperative Awareness with Explicit Recall in an Unselected Surgical Population: A Randomized Comparative Effectiveness Trial , 2012, Anesthesiology.

[33]  Steven Laureys,et al.  Diagnostic precision of PET imaging and functional MRI in disorders of consciousness: a clinical validation study , 2014, The Lancet.

[34]  C. Klein Consciousness, Intention, and Command-Following in the Vegetative State , 2017, The British Journal for the Philosophy of Science.

[35]  M. Boly,et al.  Default network connectivity reflects the level of consciousness in non-communicative brain-damaged patients. , 2010, Brain : a journal of neurology.

[36]  George A Mashour,et al.  Capturing covert consciousness , 2013, The Lancet.

[37]  Andrew Peterson Consilience, clinical validation, and global disorders of consciousness , 2016, Neuroscience of consciousness.

[38]  Matthew H. Davis,et al.  Do vegetative patients retain aspects of language comprehension? Evidence from fMRI. , 2007, Brain : a journal of neurology.

[39]  Matthew H. Davis,et al.  Response to Comments on "Detecting Awareness in the Vegetative State" , 2007, Science.

[40]  Satya Krishna Ramachandran,et al.  Assessment of Intraoperative Awareness with Explicit Recall: A Comparison of 2 Methods , 2013, Anesthesia and analgesia.

[41]  M. Boly,et al.  Willful modulation of brain activity in disorders of consciousness. , 2010, The New England journal of medicine.

[42]  Thomas E. Nichols,et al.  Can parametric statistical methods be trusted for fMRI based group studies? , 2015, 1511.01863.

[43]  Lorina Naci,et al.  Risk, diagnostic error, and the clinical science of consciousness , 2015, NeuroImage: Clinical.

[44]  Rui Dai,et al.  Disrupted neural variability during propofol‐induced sedation and unconsciousness , 2018, Human brain mapping.

[45]  Srivas Chennu,et al.  Bedside detection of awareness in the vegetative state: a cohort study , 2011, The Lancet.

[46]  P. London Injury , 1969, Definitions.

[47]  N. Juul,et al.  Regional cerebral blood flow and glucose metabolism during propofol anaesthesia in healthy subjects studied with positron emission tomography , 2012, Acta anaesthesiologica Scandinavica.

[48]  A. Owen Disorders of consciousness: Diagnostic accuracy of brain imaging in the vegetative state , 2014, Nature Reviews Neurology.

[49]  E. Shipton EXTRAORDINARY AROUSAL FROM SEMI-COMATOSE STATE ON ZOLPIDEM , 2008 .

[50]  G. Northoff,et al.  Altered temporal variance and neural synchronization of spontaneous brain activity in anesthesia , 2014, Human brain mapping.

[51]  M. Jeannerod Mental imagery in the motor context , 1995, Neuropsychologia.

[52]  Richard Rogers,et al.  Cortical and Subcortical Connectivity Changes during Decreasing Levels of Consciousness in Humans: A Functional Magnetic Resonance Imaging Study using Propofol , 2010, The Journal of Neuroscience.

[53]  Timothy O. Laumann,et al.  Functional Network Organization of the Human Brain , 2011, Neuron.

[54]  Alan C. Evans,et al.  Brain Mechanisms of Propofol-Induced Loss of Consciousness in Humans: a Positron Emission Tomographic Study , 1999, The Journal of Neuroscience.

[55]  Matthew H. Davis,et al.  Detecting awareness in the vegetative state. , 2006, Science.

[56]  N. Shea,et al.  The Vegetative State and the Science of Consciousness , 2010, The British Journal for the Philosophy of Science.

[57]  Stephen M. Rao,et al.  Propofol disrupts functional interactions between sensory and high‐order processing of auditory verbal memory , 2012, Human brain mapping.

[58]  Timothy O. Laumann,et al.  Methods to detect, characterize, and remove motion artifact in resting state fMRI , 2014, NeuroImage.

[59]  Xiao-Jing Wang,et al.  NMDA receptor function in large-scale anticorrelated neural systems with implications for cognition and schizophrenia , 2012, Proceedings of the National Academy of Sciences.

[60]  Matthew H. Davis,et al.  Towards the routine use of brain imaging to aid the clinical diagnosis of disorders of consciousness. , 2009, Brain : a journal of neurology.

[61]  N. Schiff,et al.  Dissociations between behavioural and functional magnetic resonance imaging-based evaluations of cognitive function after brain injury. , 2011, Brain : a journal of neurology.

[62]  Anthony G. Hudetz,et al.  Propofol attenuates low-frequency fluctuations of resting-state fMRI BOLD signal in the anterior frontal cortex upon loss of consciousness , 2017, NeuroImage.

[63]  Adrian M Owen,et al.  Detecting consciousness: a unique role for neuroimaging. , 2013, Annual review of psychology.

[64]  A. Owen,et al.  A Thalamocortical Mechanism for the Absence of Overt Motor Behavior in Covertly Aware Patients. , 2015, JAMA neurology.