A hidden Markov model reliably characterizes ketamine-induced spectral dynamics in macaque local field potentials and human electroencephalograms

Abstract

Ketamine is an NMDA receptor antagonist commonly used to maintain general anesthesia. At anesthetic doses, ketamine causes high power gamma (25-50 Hz) oscillations alternating with slow-delta (0.1-4 Hz) oscillations. These dynamics are readily observed in local field potentials (LFPs) of non-human primates (NHPs) and electroencephalogram (EEG) recordings from human subjects. However, a detailed statistical analysis of these dynamics has not been reported. We characterize ketamine’s neural dynamics using a hidden Markov model (HMM). The HMM observations are sequences of spectral power in seven canonical frequency bands between 0 to 50 Hz, where power is averaged within each band and scaled between 0 and 1. We model the observations as realizations of multivariate beta probability distributions that depend on a discrete-valued latent state process whose state transitions obey Markov dynamics. Using an expectation-maximization algorithm, we fit this beta-HMM to LFP recordings from 2 NHPs, and separately, to EEG recordings from 9 human subjects who received anesthetic doses of ketamine. Our beta-HMM framework provides a useful tool for experimental data analysis. Together, the estimated beta-HMM parameters and optimal state trajectory revealed an alternating pattern of states characterized primarily by gamma and slow-delta activities. The mean duration of the gamma activity was 2.2s([1.7,2.8]s) and 1.2s([0.9,1.5]s) for the two NHPs, and 2.5s([1.7,3.6]s) for the human subjects. The mean duration of the slow-delta activity was 1.6s([1.2,2.0]s) and 1.0s([0.8,1.2]s) for the two NHPs, and 1.8s([1.3,2.4]s) for the human subjects. Our characterizations of the alternating gamma slow-delta activities revealed five sub-states that show regular sequential transitions. These quantitative insights can inform the development of rhythm-generating neuronal circuit models that give mechanistic insights into this phenomenon and how ketamine produces altered states of arousal.

Proceedings of the Second Curing Coma Campaign NIH Symposium: Challenging the Future of Research for Coma and Disorders of Consciousness

“…Hence, models of propofol anesthesia have the potential to provide tremendous insights into the biology of coma. Unlike propofol, recordings during ketamine anesthesia show alternating high frequency (Gamma) oscillations and oscillations that are coordinated across the cortex from frontal to occipital regions [64]. At low doses, however, ketamine primarily only acts in the inhibitory interneurons leading to fast oscillations.…”

Dynamic reconfiguration of frequency-specific cortical coactivation patterns during psychedelic and anesthetized states induced by ketamine

“…Ketamine is a fast acting anesthetic, with a distribution half-life of only 10–15 min ( Li and Vlisides, 2016 ). We and others have shown that an anesthetic dose of ketamine induces fast transient changes in EEG signals that is characterized by alternating slow delta oscillations and gamma oscillations ( Akeju et al, 2016 ; Garwood et al, 2021 ; Li and Mashour, 2019 ; Schwartz et al, 1974 ). The objective of the current study was to use high-density EEG signals that directly measure neural activity at high temporal resolution to investigate the dynamic brain states and their reconfigurations during altered states of consciousness induced by ketamine.…”

Economic Benefit Analysis of Medical Tourism Industry Based on Markov Model

“…ere is also a 40% chance that he will need to go to the library to find reference material. en, depending on his understanding of the class content, he has a 20%, 40% and 40% chance to return to the first, second and third classes to continue his studies [9][10][11][12][13][14][15].…”