The overall goal of our work is to better understand the systems-level neuronal mechanisms by which general anesthetics produce loss of consciousness. Our general hypothesis has been that anesthetics suppress consciousness by disrupting the functioning of large-scale brain networks that support information integration in the brain.
The specific aims of the present proposal significantly advance and expand, both conceptually and experimentally, our work conducted during the period of the first award. Specifically, we intend to test if sedated participants who no longer respond behaviorally to spoken command are still able to perceive and understand environmental signals and volitionally control their mentation in a task-related manner. We will test this hypothesis by functional magnetic resonance imaging (fMRI) applied to assess the healthy participants' (healthy volunteers) ability to generate willful, neuroanatomically specific, blood-oxygen-level dependent (BOLD) responses during two established mental-imagery tasks (playing tennis and spatial navigation). We hypothesize that under specific conditions of sedation, subjects will retain their capacity for mental imagery despite their failure to initiate an overt response. If so, then the new findings may induce a paradigm shift in the clinical assessment of consciousness in anesthesia. They would also establish validation for monitoring disorders of consciousness and establish generality of the finding between disorders of consciousness and general anesthesia. As a second aim, we intend to determine for the first time, the neural conditions for the participants' ability for volitional mental imagery. We hypothesize that spontaneous fluctuations of brain states during sedation directly influence and predict the participants' ability for mental imagery. If confirmed, this would imply a novel causal link between the state of intrinsic network activity and volitional mental activity in reduced states of consciousness. This would have extremely important translational significance for optimizing brain-computer interfaces for the aid of patients with behavioral compromise or reduced consciousness. Finally, in a third aim, we will determine the neural correlates of distorted perception under sedation using complex, temporally structured stimuli such as music. The latter studies should yield insight into how sedation may alter the temporal integration of complex stimuli supporting conscious experience. Taken together, the project should significantly advance our understanding of the fundamental neuronal mechanisms of anesthetic modulation of conscious cognition with a significant translational and paradigmatic impact for the clinical assessment of the state of consciousness and for the potential communication of patients via volitional mental activity.

Public Health Relevance

This research project should help us better understand what happens to the thinking brain when the patient is anesthetized. The project will use cognitive testing and noninvasive functional magnetic resonance imaging of the brain to help understand how general anesthetics suppress consciousness and how consciousness returns after the termination of sedation. Using anesthetic drugs as investigational tools, the knowledge gained should help better understand the neuronal mechanisms human consciousness and anesthesia and help develop novel approaches to assess residual cognitive functioning in sedated patients. The findings will have important clinical translational implications to neurological patients with disordered consciousness and to aid the interaction with non-communicating patients via brain-computer interface.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Justinova, Zuzana
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Michigan Ann Arbor
Schools of Medicine
Ann Arbor
United States
Zip Code
Huang, Zirui; Zhang, Jun; Wu, Jinsong et al. (2018) Disrupted neural variability during propofol-induced sedation and unconsciousness. Hum Brain Mapp 39:4533-4544
Huang, Zirui; Liu, Xiaolin; Mashour, George A et al. (2018) Timescales of Intrinsic BOLD Signal Dynamics and Functional Connectivity in Pharmacologic and Neuropathologic States of Unconsciousness. J Neurosci 38:2304-2317
Huang, Zirui; Vlisides, Phillip E; Tarnal, Vijaykumar C et al. (2018) Brain imaging reveals covert consciousness during behavioral unresponsiveness induced by propofol. Sci Rep 8:13195
Liu, Xiaolin; Lauer, Kathryn K; Ward, B Douglas et al. (2018) Regional entropy of functional imaging signals varies differently in sensory and cognitive systems during propofol-modulated loss and return of behavioral responsiveness. Brain Imaging Behav :
Pal, Dinesh; Silverstein, Brian H; Sharba, Lana et al. (2017) Propofol, Sevoflurane, and Ketamine Induce a Reversible Increase in Delta-Gamma and Theta-Gamma Phase-Amplitude Coupling in Frontal Cortex of Rat. Front Syst Neurosci 11:41
Mashour, George A; Hudetz, Anthony G (2017) Bottom-Up and Top-Down Mechanisms of General Anesthetics Modulate Different Dimensions of Consciousness. Front Neural Circuits 11:44
Liu, Xiaolin; Li, Shi-Jiang; Shaker, Reza et al. (2017) Reduced Functional Connectivity Between the Hypothalamus and High-order Cortical Regions in Adolescent Patients With Irritable Bowel Syndrome. J Pediatr Gastroenterol Nutr 65:516-519
Liu, Xiaolin; Lauer, Kathryn K; Douglas Ward, B et al. (2017) Propofol attenuates low-frequency fluctuations of resting-state fMRI BOLD signal in the anterior frontal cortex upon loss of consciousness. Neuroimage 147:295-301
Liu, Xiaolin; Lauer, Kathryn K; Ward, B Douglas et al. (2017) Fine-Grained Parcellation of Brain Connectivity Improves Differentiation of States of Consciousness During Graded Propofol Sedation. Brain Connect 7:373-381
Liu, X; Silverman, A; Kern, M et al. (2016) Excessive coupling of the salience network with intrinsic neurocognitive brain networks during rectal distension in adolescents with irritable bowel syndrome: a preliminary report. Neurogastroenterol Motil 28:43-53

Showing the most recent 10 out of 30 publications