Potential Mechanisms for the Ketamine-Induced Reduction of P3b Amplitudes.
Timm Rosburg, André Schmidt
Frontiers in Behavioral Neuroscience 2018 DOI: 10.3389/fnbeh.2018.00308 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Intervention | Ketamine |
| Measures | P3b, P3a, P1, N1 |
| Topics | Ketamine Esketamine |
| Keywords | N-methyl-d-aspartate Schizophrenia Event-related potentials Model psychosis Task difficulty Working memory |
| Key findings | The authors argue that ketamine's reduction of P3b amplitude to target stimuli cannot be explained by a drug-induced increase in task difficulty, because increased task difficulty raises P3a amplitude to same-modality distractors while ketamine lowers it. They propose that the combined reductions in P3a and P3b instead point to impaired working memory updating after ketamine, consistent with prior behavioral findings. |
Abstract
In specific dosages, the N-methyl-D-aspartate receptor (NMDA) antagonist ketamine can be used to model transient psychotic symptoms in healthy individuals that resemble those of schizophrenia. Ketamine administration also temporarily impairs cognitive functions, which can be studied by event-related potentials (ERPs). ERPs also allow dissecting what stages of information processing are affected by ketamine and what stages remain functional. For tasks requiring the differentiation of targets and non-targets, it has repeatedly been shown that ketamine administration in healthy individuals leads to decreased amplitudes of the ERP component P3b in response to target stimuli. However, it could be argued that this ketamine-induced P3b reduction is the consequence of an increased difficulty to differentiate targets from non-targets, primarily mediated by ketamine's psychotomimetic rather than pharmacological effects. The current review of ERP studies seeks to clarify the issue whether P3b effects of ketamine may indeed be explained as the consequence of an experienced increase in task difficulty or whether alternative mechanisms are perhaps more plausible. The review first summarizes the effects of task difficulty on ERP components related to intentional stimulus categorization (P3b), involuntary attention switches to distractors (P3a), as well as sensory processing (P1, N1). Secondly, the ERP effects of task difficulty are contrasted with those observed in ketamine studies in healthy individuals. Findings show that P3b amplitudes are consistently diminished by an increased task difficulty, as well as after ketamine administration. In contrast and as most important difference, increased task difficulty leads to increased P3a amplitudes to distractors presented in same modality as targets, whereas ketamine leads to reduced P3a amplitudes for such distractors. This dissociation indicates that the decreased P3b amplitudes after ketamine cannot be explained by a drug-induced increase in task difficulty. The conjoint reductions of P3a and P3b amplitudes instead suggest that working memory operations, in particular working memory updating are impaired after ketamine, which is in line with previous behavioral findings.
Comparable studies
Other narrative reviews on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms | 2018 | Review | |
| Mechanisms of Ketamine Action as an Antidepressant | 2018 | Review | |
| Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation Adults with treatment-resistant depression | 2021 | Review | |
| Ketamine Pharmacology: An Update (Pharmacodynamics and Molecular Aspects, Recent Findings) | 2013 | Review | |
| A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders | 2017 | Review and consensus statement |
Citations in the library
Cited by 4
- Ketamine Affects Prediction Errors about Statistical Regularities: A Computational Single-Trial Analysis of the Mismatch Negativity Journal of Neuroscience June 19, 2020
- Glutamatergic mechanisms in early salience processing. Frontiers in Pharmacology 2025
- Effects of Glycine on Mismatch Negativity and the Underlying Theta-Band Signature in the Ketamine Model of Schizophrenia in Healthy Men. Schizophrenia Bulletin December 14, 2025
- N-methyl-d-aspartate receptor antagonism modulates P300 event-related potentials and associated activity in salience and central executive networks. Pharmacology, Biochemistry, and Behavior October 1, 2021
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and 6 more in the library