Perioperative Medicine  |   November 2018
Resting-state Dynamics as a Cortical Signature of Anesthesia in Monkeys
Author Notes
  • From Commissariat à l'Énergie Atomique et aux Énergies Alternatives, Direction de la Recherche Fondamentale, NeuroSpin Center, Gif-sur-Yvette, France (L.U., A.J., J.T., P.B., M.D., S.D., B.J.); Cognitive Neuroimaging Unit, Institut National de la Santé et de la Recherche Médicale U992, Gif-sur-Yvette, France (L.U., A.J., J.T., P.B., M.D., S.D., B.J.); Department of Anesthesiology and Critical Care, Necker Hospital, University Paris Descartes, Paris, France (L.U.); Department of Anesthesiology and Critical Care, Sainte-Anne Hospital, University Paris Descartes, Paris, France (L.U.); Institut National de la Santé et de la Recherche Médicale U1127, Paris, France (J.D.S.); Physiological Investigations of Clinically Normal and Impaired Cognition Lab, Institut du Cerveau et de la Moelle épinière, Paris, France (J.D.S.); Collège de France, Paris, France (S.D.); Université Paris Sud, Université Paris-Saclay, Orsay, France (S.D.); Neurosurgery Department, Foch Hospital, Suresnes, France (B.J.); and the University of Versailles Saint-Quentin-en-Yvelines, Université Paris-Saclay, Versailles, France (B.J.).
  • This article is featured in “This Month in Anesthesiology,” page 1A.
    This article is featured in “This Month in Anesthesiology,” page 1A.×
  • Corresponding article on page 869.
    Corresponding article on page 869.×
  • Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are available in both the HTML and PDF versions of this article. Links to the digital files are provided in the HTML text of this article on the Journal’s Web site (www.anesthesiology.org).
    Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are available in both the HTML and PDF versions of this article. Links to the digital files are provided in the HTML text of this article on the Journal’s Web site (www.anesthesiology.org).×
  • The work in this article has been presented as a poster presentation at the Euroanesthesia Meeting in London, United Kingdom, May 28, 2016, and as an oral presentation at the meeting of the French Society of Anesthesia and Critical Care in Paris, France, September 22, 2016. L.U., J.D.S., and A.J. contributed equally to this article.
    The work in this article has been presented as a poster presentation at the Euroanesthesia Meeting in London, United Kingdom, May 28, 2016, and as an oral presentation at the meeting of the French Society of Anesthesia and Critical Care in Paris, France, September 22, 2016. L.U., J.D.S., and A.J. contributed equally to this article.×
  • Address correspondence to Dr. Jarraya: CEA Paris-Saclay, NeuroSpin, Bat 145, 91191 Gif-sur-Yvette, France. bechir.jarraya@cea.fr. 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 / Basic Science / Pharmacology
Perioperative Medicine   |   November 2018
Resting-state Dynamics as a Cortical Signature of Anesthesia in Monkeys
Anesthesiology 11 2018, Vol.129, 942-958. doi:10.1097/ALN.0000000000002336
Anesthesiology 11 2018, Vol.129, 942-958. doi:10.1097/ALN.0000000000002336
Abstract

Editor’s Perspective:

What We Already Know about This Topic:

  • Anesthesia-induced loss of consciousness is paralleled by a disruption of frontoparietal functional correlation, as measured by functional magnetic resonance imaging and electroencephalography. However, it is still unclear how anesthesia induces such a corticocortical disconnection.

  • Dynamic-resting state is a recent analytical method to study large-scale brain networks, allowing the clustering of functional magnetic resonance images into functional brain states.

What This Article Tells Us That Is New:

  • When moving from wakefulness to anesthesia, the anatomical structure of connections between brain areas becomes the main driver of the repertoire of functional states. Subjects given anesthesia lose the ability to generate flexible functional brain states that transcend brain anatomy.

  • High similarity between brain structure and function is a new general signature of anesthesia-induced loss of consciousness.

Background: The mechanism by which anesthetics induce a loss of consciousness remains a puzzling problem. We hypothesized that a cortical signature of anesthesia could be found in an increase in similarity between the matrix of resting-state functional correlations and the anatomical connectivity matrix of the brain, resulting in an increased function-structure similarity.

Methods: We acquired resting-state functional magnetic resonance images in macaque monkeys during wakefulness (n = 3) or anesthesia with propofol (n = 3), ketamine (n = 3), or sevoflurane (n = 3). We used the k-means algorithm to cluster dynamic resting-state data into independent functional brain states. For each condition, we performed a regression analysis to quantify function-structure similarity and the repertoire of functional brain states.

Results: Seven functional brain states were clustered and ranked according to their similarity to structural connectivity, with higher ranks corresponding to higher function-structure similarity and lower ranks corresponding to lower correlation between brain function and brain anatomy. Anesthesia shifted the brain state composition from a low rank (rounded rank [mean ± SD]) in the awake condition (awake rank = 4 [3.58 ± 1.03]) to high ranks in the different anesthetic conditions (ketamine rank = 6 [6.10 ± 0.32]; moderate propofol rank = 6 [6.15 ± 0.76]; deep propofol rank = 6 [6.16 ± 0.46]; moderate sevoflurane rank = 5 [5.10 ± 0.81]; deep sevoflurane rank = 6 [5.81 ± 1.11]; P < 0.0001).

Conclusions: Whatever the molecular mechanism, anesthesia led to a massive reconfiguration of the repertoire of functional brain states that became predominantly shaped by brain anatomy (high function-structure similarity), giving rise to a well-defined cortical signature of anesthesia-induced loss of consciousness.