Newly Published
Perioperative Medicine  |   February 2020
Dynamics of Ketamine-induced Loss and Return of Consciousness across Primate Neocortex
Author Notes
  • From the Department of Anesthesia, Critical Care and Pain Medicine (J.J.B., Y.I.), and the Department of Neurology (S.R.P.), Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; the Department of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California (P.H.); and the Departments of Neurological Surgery, Neuroscience, Psychiatry and Behavioral Sciences, Albert Einstein College of Medicine, Bronx, New York (E.N.E.)
  • Part of the work presented in this article was presented at the Anesthesiology Annual Meeting in Boston, Massachusetts, October 21 to 25, 2017, and a part of the work was selected into the Best Abstracts Session for Basic Sciences at the Anesthesiology Annual Meeting in Orlando, Florida, October 19 to 23, 2019.
    Part of the work presented in this article was presented at the Anesthesiology Annual Meeting in Boston, Massachusetts, October 21 to 25, 2017, and a part of the work was selected into the Best Abstracts Session for Basic Sciences at the Anesthesiology Annual Meeting in Orlando, Florida, October 19 to 23, 2019.×
  • Submitted for publication July 26, 2019. Accepted for publication December 20, 2019.
    Submitted for publication July 26, 2019. Accepted for publication December 20, 2019.×
  • Correspondence: Address correspondence to Dr. Ishizawa: Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, 55 Fruit Street Gray Jackson 444, Boston, Massachusetts 02114. yishizawa@mgh.harvard.edu. 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   |   February 2020
Dynamics of Ketamine-induced Loss and Return of Consciousness across Primate Neocortex
Anesthesiology Newly Published on February 11, 2020. doi:https://doi.org/10.1097/ALN.0000000000003159
Anesthesiology Newly Published on February 11, 2020. doi:https://doi.org/10.1097/ALN.0000000000003159
Abstract

Background: Ketamine is a noncompetitive N-methyl-d-aspartate antagonist and is known for unique electrophysiologic profiles in electroencephalography. However, the mechanisms of ketamine-induced unconsciousness are not clearly understood. The authors have investigated neuronal dynamics of ketamine-induced loss and return of consciousness and how multisensory processing is modified in the primate neocortex.

Methods: The authors performed intracortical recordings of local field potentials and single unit activity during ketamine-induced altered states of consciousness in a somatosensory and ventral premotor network. The animals were trained to perform a button holding task to indicate alertness. Air puff to face or sound was randomly delivered in each trial regardless of their behavioral response. Ketamine was infused for 60 min.

Results: Ketamine-induced loss of consciousness was identified during a gradual evolution of the high beta-gamma oscillations. The slow oscillations appeared to develop at a later stage of ketamine anesthesia. Return of consciousness and return of preanesthetic performance level (performance return) were observed during a gradual drift of the gamma oscillations toward the beta frequency. Ketamine-induced loss of consciousness, return of consciousness, and performance return are all identified during a gradual change of the dynamics, distinctive from the abrupt neural changes at propofol-induced loss of consciousness and return of consciousness. Multisensory responses indicate that puff evoked potentials and single-unit firing responses to puff were both preserved during ketamine anesthesia, but sound responses were selectively diminished. Units with suppressed responses and those with bimodal responses appeared to be inhibited under ketamine and delayed in recovery.

Conclusions: Ketamine generates unique intracortical dynamics during its altered states of consciousness, suggesting fundamentally different neuronal processes from propofol. The gradually shifting dynamics suggest a continuously conscious or dreaming state while unresponsive under ketamine until its deeper stage with the slow-delta oscillations. Somatosensory processing is preserved during ketamine anesthesia, but multisensory processing appears to be diminished under ketamine and through recovery.

Editor’s Perspective:

What We Already Know about This Topic:

  • Ketamine increases both fast and slow oscillations in the primate brain, but the neural correlates of ketamine-induced state transitions have not been precisely characterized

What This Article Tells Us That Is New:

  • In a study of nonhuman primates and continuous ketamine administration, the authors demonstrate a unique and gradual evolution of high-frequency and low-frequency neural activity, which distinguish the effects of ketamine from the dynamics of propofol-induced unconsciousness