Subanaesthetic doses of ketamine reduce but do not eliminate predictive coding responses: implications for mechanisms of sensory disconnection.
Jordan J Wehrman, Cameron P Casey, Sean Tanabe, Sounak Mohanta, William Filbey, Lilian Weber, Matthew I Banks, Robert A Pearce, Yuri B Saalmann, Robert D. Sanders
British Journal of Anaesthesia October 2023 DOI: 10.1016/j.bja.2023.06.044 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Within-subject experimental study Peer reviewed |
|---|---|
| Sample size | 14 |
| Population | Healthy human participants receiving subanaesthetic ketamine infusions |
| Intervention | Ketamine |
| Dose | blood concentration up to 0.3 μg/ml; effects reported at 0.2-0.3 μg/ml |
| Measures | electroencephalography evoked response potentials |
| Topics | Ketamine Esketamine |
| Keywords | Nmda Electroencephalography Hierarchical gaussian filter Mismatch negativity Predictive coding Sensory disconnection |
| Registration | NCT03284307 |
| Key findings | Subanaesthetic ketamine reduced electroencephalographic correlates of prediction error related to transitional probability at blood concentrations of 0.2-0.3 μg/ml, but did not eliminate them, and did not modulate prediction errors related to environmental volatility in a dose-dependent manner. The authors argue that predictive coding is diminished but not abolished at doses that do not induce sensory disconnection. |
Abstract
Sensory disconnection is a key feature of sleep and anaesthesia. We have proposed that predictive coding offers a framework for understanding the mechanisms of disconnection. Low doses of ketamine that do not induce disconnection should thus diminish predictive coding, but not abolish it. Ketamine was administered to 14 participants up to a blood concentration of 0.3 μg ml-1 Participants were played a series of tones comprising a roving oddball sequence while electroencephalography evoked response potentials were recorded. We fit a Bayesian observer model to the tone sequence, correlating neural activity with the prediction errors generated by the model using linear mixed effects models and cluster-based statistics. Ketamine modulated prediction errors associated with the transition of one tone to the next (transitional probability), but not how often tones changed (environmental volatility), of the system. Transitional probability was reduced when blood concentrations of ketamine were increased to 0.2-0.3 μg ml-1 (96-208 ms, P=0.003); however, correlates of prediction error were still evident in the electroencephalogram (124-168 ms, P=0.003). Prediction errors related to environmental volatility were associated with electroencephalographic activity before ketamine (224-284 ms, P=0.028) and during 0.2-0.3 μg ml-1 ketamine (108-248 ms, P=0.003). At this subanaesthetic dose, ketamine did not exert a dose-dependent modulation of prediction error. Subanaesthetic dosing of ketamine reduced correlates of predictive coding but did not eliminate them. Future studies should evaluate whether states of sensory disconnection, including anaesthetic doses of ketamine, are associated with a complete absence of predictive coding responses. NCT03284307.
Comparable studies
Other experimental studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Ketamine activates psychosis and alters limbic blood flow in schizophrenia Schizophrenic individuals | 1995 | Experimental study | |
| The spectral exponent of the resting EEG indexes the presence of consciousness during unresponsiveness induced by propofol, xenon, and ketamine Healthy participants | 2019 | Controlled experimental study | n = 15 |
| Ketamine Increases Human Motor Cortex Excitability to Transcranial Magnetic Stimulation Normal human subjects | 2003 | Experimental study | n = 7 |
| Evidence that Subanesthetic Doses of Ketamine Cause Sustained Disruptions of NMDA and AMPA-Mediated Frontoparietal Connectivity in Humans Human participants | 2015 | Experimental study | |
| Simultaneous population pharmacokinetic modelling of ketamine and three major metabolites in patients with treatment‐resistant bipolar depression Patients with treatment-resistant bipolar depression | 2012 | Population pharmacokinetic analysis | n = 9 |
Citations in the library
Cites 7
- The effects of ketamine on dopaminergic function: meta-analysis and review of the implications for neuropsychiatric disorders Molecular Psychiatry October 3, 2017
- Ketamine Affects Prediction Errors about Statistical Regularities: A Computational Single-Trial Analysis of the Mismatch Negativity Journal of Neuroscience June 19, 2020
- Evoked Alpha Power is Reduced in Disconnected Consciousness During Sleep and Anesthesia Scientific Reports November 5, 2018
- Effects of Subanesthetic Ketamine Administration on Visual and Auditory Event-Related Potentials (ERP) in Humans: A Systematic Review Frontiers in Behavioral Neuroscience April 16, 2018
- Ephenidine: A new psychoactive agent with ketamine-like NMDA receptor antagonist properties Neuropharmacology August 10, 2016
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