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Dynamics of Ketamine-induced Loss and Return of Consciousness across Primate Neocortex.

Jesus J Ballesteros, Pamela Huang, Shaun R Patel, Emad N. Eskandar, Yumiko Ishizawa

Anesthesiology April 2020 DOI: 10.1097/aln.0000000000003159 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Observational animal study with intracortical electrophysiological recordings Peer reviewed
Population Primates trained to perform a button-holding task indicating alertness
Intervention Ketamine
Duration 60-minute ketamine infusion
Topics Esketamine Ketamine
Key findings Ketamine-induced loss and return of consciousness in primates evolved gradually alongside shifting beta-gamma oscillations, distinct from the abrupt changes reported with propofol. Somatosensory puff-evoked responses were preserved during anesthesia, but sound responses were selectively diminished, and suppressed or bimodal units were inhibited and slow to recover. The authors suggest the gradual dynamics may reflect a continuously conscious or dreaming state while unresponsive.

Abstract

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. 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. 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. 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.

Comparable studies

Other preclinical and animal studies on ketamine, most cited first.

Study Year Design Participants
mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats 2010 Observational study
Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats 1997 Dose-response study with microdialysis and behavioral testing
NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice 2016 Preclinical study
The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats 1983 Experimental study
R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice 2015 Experimental study

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Esketamine Ketamine Altered states of consciousness Dreaming Lucid dreaming