Newly Published
Perioperative Medicine  |   March 2020
Altered Global Brain Signal during Physiologic, Pharmacologic, and Pathologic States of Unconsciousness in Humans and Rats
Author Notes
  • From the Department of Anesthesiology, Huashan Hospital, Fudan University, Shanghai, China (J.Z., Y.C., J.X.); the Department of Anesthesiology and Center for Consciousness Science, University of Michigan, Ann Arbor, Michigan (S.T., Z.H., G.A.M., A.G.H.); Institute of Mental Health Research (S.F., G.N.), School of Psychology (S.F.), University of Ottawa, Ottawa, Canada; Department of Psychology, University of Montreal, Montreal, Canada (S.F., J.D.); Functional Neuroimaging Unit, Institute of Geriatrics, University of Montréal, Montréal, Canada (S.F., J.D.); McConnell Brain Imaging Center, Montreal Neurological Institute, McGill University, Montreal, Canada (J.D.); Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China (J.W., X.W., Y.M.); Mental Health Center, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China (J.Z., G.N.); School of Psychology, South China Normal University, Guangzhou, Guangdong, China (P.Q.).
  • S.T. and Z.H. contributed equally to this article.
    S.T. and Z.H. contributed equally to this article.×
  • Submitted for publication June 27, 2019. Accepted for publication January 16, 2020.
    Submitted for publication June 27, 2019. Accepted for publication January 16, 2020.×
  • Correspondence: Address correspondence to Dr. Zhang: Department of Anesthesiology, Huashan Hospital, Fudan University, #12, Wulumuqi Middle Road, Shanghai, 200040, China. snapzhang@aliyun.com. Information on purchasing reprints may be found at www.anesthesiology.org or on the masthead page at the beginning of this issue. Anesthesiology’s articles are made freely accessible to all readers, for personal use only, 6 months from the cover date of the issue.
Article Information
Perioperative Medicine / Central and Peripheral Nervous Systems / Pharmacology
Perioperative Medicine   |   March 2020
Altered Global Brain Signal during Physiologic, Pharmacologic, and Pathologic States of Unconsciousness in Humans and Rats
Anesthesiology Newly Published on March 19, 2020. doi:https://doi.org/10.1097/ALN.0000000000003197
Anesthesiology Newly Published on March 19, 2020. doi:https://doi.org/10.1097/ALN.0000000000003197
Abstract

Background: Consciousness is supported by integrated brain activity across widespread functionally segregated networks. The functional magnetic resonance imaging–derived global brain signal is a candidate marker for a conscious state, and thus the authors hypothesized that unconsciousness would be accompanied by a loss of global temporal coordination, with specific patterns of decoupling between local regions and global activity differentiating among various unconscious states.

Methods: Functional magnetic resonance imaging global signals were studied in physiologic, pharmacologic, and pathologic states of unconsciousness in human natural sleep (n = 9), propofol anesthesia (humans, n = 14; male rats, n = 12), and neuropathological patients (n = 21). The global signal amplitude as well as the correlation between global signal and signals of local voxels were quantified. The former reflects the net strength of global temporal coordination, and the latter yields global signal topography.

Results: A profound reduction of global signal amplitude was seen consistently across the various unconscious states: wakefulness (median [1st, 3rd quartile], 0.46 [0.21, 0.50]) versus non-rapid eye movement stage 3 of sleep (0.30 [0.24, 0.32]; P = 0.035), wakefulness (0.36 [0.31, 0.42]) versus general anesthesia (0.25 [0.21, 0.28]; P = 0.001), healthy controls (0.30 [0.27, 0.37]) versus unresponsive wakefulness syndrome (0.22 [0.15, 0.24]; P < 0.001), and low dose (0.07 [0.06, 0.08]) versus high dose of propofol (0.04 [0.03, 0.05]; P = 0.028) in rats. Furthermore, non-rapid eye movement stage 3 of sleep was characterized by a decoupling of sensory and attention networks from the global network. General anesthesia and unresponsive wakefulness syndrome were characterized by a dissociation of the majority of functional networks from the global network. This decoupling, however, was dominated by distinct neuroanatomic foci (e.g., precuneus and anterior cingulate cortices).

Conclusions: The global temporal coordination of various modules across the brain may distinguish the coarse-grained state of consciousness versus unconsciousness, while the relationship between the global and local signals may define the particular qualities of a particular unconscious state.

Editor’s Perspective:

What We Already Know about This Topic:

  • Integrated neuronal activity across functionally distinct brain networks is a prerequisite for consciousness

  • Functional magnetic resonance imaging–derived global brain signal is a candidate marker for conscious states

  • Whether unconsciousness is correlated with a loss of global temporal coordination of brain activities has not been previously reported

What This Article Tells Us That Is New:

  • Functional magnetic resonance imaging of global brain signal amplitude and functional connectivity demonstrates a strong association between overall brain connectivity and the level of consciousness in both humans and rats

  • Each distinct state of unconsciousness, including sleep, general anesthesia, and unresponsive wakefulness syndrome, showed state-specific alterations in global signal topography

  • These findings suggest that the global temporal coordination defines the coarse-grained state of consciousness versus unconsciousness, while the relationship of the global and local signals defines the particular qualities of that unconscious state