Differential Effects of Propofol and Ketamine on Critical Brain Dynamics

Thomas F. Varley; Olaf Sporns; Aina Puce; John Beggs

doi:10.1101/2020.03.27.012070

Differential Effects of Propofol and Ketamine on Critical Brain Dynamics

Thomas F. Varley, Olaf Sporns, Aina Puce, John Beggs

bioRxiv Preprint Server March 27, 2020 preprint DOI: 10.1101/2020.03.27.012070 (opens in new tab)

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AI-extracted from the abstract

Characteristics	Observational study
Sample size	1
Population	Single macaque
Interventions	Propofol Ketamine
Topics	Ketamine Esketamine
Keywords	Consciousness Awareness Sentience Cognition Mind Perception Brain dynamics Brain activity Neural networks Brain states Brain function Neural dynamics Anesthesia Sedation Drug effects Propofol Anesthetics Brain research Neurobiology Cognitive neuroscience Brain science
Citations	3
Key findings	Propofol, but not ketamine, dramatically restricted avalanche size and duration and reduced brain dynamics complexity, yet all states retained some signs of criticality.

Abstract

Whether the brain operates at a critical ‘‘tipping” point is a long standing scientific question, with evidence from both cellular and systems-scale studies suggesting that the brain does sit in, or near, a critical regime. Neuroimaging studies of humans in altered states of consciousness have prompted the suggestion that maintenance of critical dynamics is necessary for the emergence of consciousness and complex cognition, and that reduced or disorganized consciousness may be associated with deviations from criticality. Unfortunately, many of the cellular-level studies reporting signs of criticality were performed in non-conscious systems (in vitro neuronal cultures) or unconscious animals (e.g. anaesthetized rats). Here we attempted to address this knowledge gap by exploring critical brain dynamics in invasive ECoG recordings from multiple sessions with a single macaque as the animal transitioned from consciousness to unconsciousness under different anaesthetics (ketamine and propofol). We use a previously-validated test of criticality: avalanche dynamics to assess the differences in brain dynamics between normal consciousness and both drug-states. Propofol and ketamine were selected due to their differential effects on consciousness (ketamine, but not propofol, is known to induce an unusual state known as ‘dissociative anaesthesia”). Our analyses indicate that propofol dramatically restricted the size and duration of avalanches, while ketamine allowed for more awake-like dynamics to persist. In addition, propofol, but not ketamine, triggered a large reduction in the complexity of brain dynamics. All states, however, showed some signs of persistent criticality when testing for exponent relations and universal shape-collapse. Further, maintenance of critical brain dynamics may be important for regulation and control of conscious awareness.

Comparable studies

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

Study	Year	Design
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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