Analysis of the Hindriks and van Putten model for propofol anesthesia: Limitations and extensions

• Published in: NeuroImage (Orlando, Fla.) Vol. 227; p. 117633
• Main Authors: Noroozbabaee, Leyla, Steyn-Ross, D.A., Steyn-Ross, Moira L., Sleigh, J.W.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.02.2021; Elsevier Limited; Elsevier
• Subjects: Anesthesia; Anesthetics, Intravenous - pharmacology; Cerebral Cortex - drug effects; Cerebral Cortex - physiology; Coma; Consciousness; EEG; Fainting; Firing pattern; Firing rate; General anesthesia; Humans; Light effects; Models, Neurological; Nerve Net - drug effects; Nerve Net - physiology; Neural Inhibition - drug effects; Neural Inhibition - physiology; Neuroimaging; Neurons; Neurons - drug effects; Neurons - physiology; Ordinary differential equations; Phase transitions; Population; Propagation; Propofol; Propofol - pharmacology; Thalamocortical mean-field model; Thalamus; γ-Aminobutyric acid A receptors; Thalamocortical mean-field model; Anesthesia; Propofol; EEG
• ISSN: 1053-8119; 1095-9572
• DOI: 10.1016/j.neuroimage.2020.117633

[Display omitted] We present a detailed analysis of the Hindriks and van Putten thalamocortical mean-field model for propofol anesthesia [NeuroImage 60(23), 2012]. The Hindriks and van Putten (HvP) model predicts increases in delta and alpha power for moderate (up to 130%) prolongation of GABAA inhibitory response, corresponding to light anesthetic sedation. Our analysis reveals that, for deeper anesthetic effect, the model exhibits an unexpected abrupt jump in cortical activity from a low-firing state to an extremely high-firing stable state (∼250 spikes/s), and remains locked there even at GABAA prolongations as high as 300% which would be expected to induce full comatose suppression of all firing activity. We demonstrate that this unphysiological behavior can be completely suppressed with appropriate tuning of the parameters controlling the sigmoidal functions that map soma voltage to firing rate for the excitatory and inhibitory neural populations, coupled with elimination of the putative population-dependent anesthetic efficacies introduced in the HvP model. The modifications reported here constrain the anesthetized brain activity into a biologically plausible range in which the cortex now has access to a moderate-firing state (“awake”) and a low-firing (“anesthetized”) state such that the brain can transition from “awake” to “anesthetized” states at a critical level of drug concentration. The modified HvP model predicts a drug–effect hysteresis in which the drug concentration required for induction is larger than that at emergence. In addition, the revised model shows a decrease in the intensity and frequency of alpha-band fluctuations, transitioning to delta-band dominance, with deepening anesthesia. These predicted drug concentration-dependent changes in EEG dynamics are consistent with clinical reports.