A hidden Markov model reliably characterizes ketamine-induced spectral dynamics in macaque LFP and human EEG
Indie C. Garwood, S. Chakravarty, Jacob Donoghue, Pegah Kahali, Shubham Chamadia, Oluwaseun Akeju, Earl K. Miller, Emery N Brown
medRxiv November 16, 2020 preprint DOI: 10.1101/2020.11.12.20221366 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational study |
|---|---|
| Sample size | 11 |
| Population | 2 non-human primates and 9 human subjects receiving anesthetic doses of ketamine |
| Intervention | Ketamine |
| Topics | Esketamine Ketamine |
| Key findings | The beta-HMM revealed alternating gamma-burst and slow-oscillation states with intermediate states. Mean gamma-burst state durations were 2.5s and 1.2s for the two NHPs, and 2.7s for humans; mean slow-oscillation state durations were 1.6s and 0.7s for NHPs, and 2.8s for humans. |
Abstract
Abstract Ketamine is an NMDA receptor antagonist commonly used to maintain general anesthesia. At anesthetic doses, ketamine causes bursts of 30-50 Hz oscillations alternating with 0.1 to 10 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 10 Hz 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. Together, the estimated beta-HMM parameters and optimal state trajectory revealed an alternating pattern of states characterized primarily by gamma burst and slow oscillation activity, as well as intermediate states in between. The mean duration of the gamma burst state was 2.5s([1.9,3.4]s) and 1.2s([0.9,1.5]s) for the two NHPs, and 2.7s([1.9,3.8]s) for the human subjects. The mean duration of the slow oscillation state was 1.6s([1.1,2.5]s) and 0.7s([0.6,0.9]s) for the two NHPs, and 2.8s([1.9,4.3]s) for the human subjects. Our beta-HMM framework provides a useful tool for experimental data analysis. Our characterizations of the gamma-burst process offer detailed, quantitative constraints that 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.
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 |
Citations in the library
Cites 7
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- Taming the Ketamine Tiger Anesthesiology August 6, 2010
- Reviewing the ketamine model for schizophrenia Journal of Psychopharmacology November 20, 2013
- Cortical dynamics during psychedelic and anesthetized states induced by ketamine Neuroimage April 5, 2019
- Ketamine as a Fast Acting Antidepressant: Current Knowledge and Open Questions CNS Neuroscience & Therapeutics April 12, 2013
and 2 more in the library