Temporal dynamics of the pharmacological MRI response to subanaesthetic ketamine in healthy volunteers: A simultaneous EEG/fMRI study
Rebecca McMillan, Anna Forsyth, Doug Campbell, Gemma Malpas, Elizabeth A. Maxwell, Juergen Dukart, Joerg F. Hipp, Suresh Muthukumaraswamy
Journal of Psychopharmacology January 21, 2019 DOI: 10.1177/0269881118822263 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Sample size | 30 |
| Population | Healthy male participants |
| Intervention | subanaesthetic intravenous ketamine infusion |
| Dose | subanaesthetic intravenous ketamine infusion |
| Topics | Ketamine Esketamine |
| Keywords | Blood-oxygen-level dependent Electroencephalography Anterior cingulate cortex Magnetic resonance imaging EEG-FMRI Anesthesia Cognition Radiology |
| Citations | 23 |
| Key findings | Ketamine-induced decreases in subgenual anterior cingulate cortex blood-oxygen-level dependent signal are largely attributable to physiological noise, and a single temporal model does not capture the full spectrum of neural dynamics. |
Abstract
Background: Pharmacological magnetic resonance imaging has been used to investigate the neural effects of subanaesthetic ketamine in healthy volunteers. However, the effect of ketamine has been modelled with a single time course and without consideration of physiological noise.
Aims: This study aimed to investigate ketamine-induced alterations in resting neural activity using conventional pharmacological magnetic resonance imaging analysis techniques with physiological noise correction, and a novel analysis utilising simultaneously recorded electroencephalography data.
Methods: Simultaneous electroencephalography/functional magnetic resonance imaging and physiological data were collected from 30 healthy male participants before and during a subanaesthetic intravenous ketamine infusion.
Results: Consistent with previous literature, we show widespread cortical blood-oxygen-level dependent signal increases and decreased blood-oxygen-level dependent signals in the subgenual anterior cingulate cortex following ketamine. However, the latter effect was attenuated by the inclusion of motion regressors and physiological correction in the model. In a novel analysis, we modelled the pharmacological magnetic resonance imaging response with the power time series of seven electroencephalography frequency bands. This showed evidence for distinct temporal time courses of neural responses to ketamine. No electroencephalography power time series correlated with decreased blood-oxygen-level dependent signal in the subgenual anterior cingulate cortex.
Conclusions: We suggest the decrease in blood-oxygen-level dependent signals in the subgenual anterior cingulate cortex typically seen in the literature is the result of physiological noise, in particular cardiac pulsatility. Furthermore, modelling the pharmacological magnetic resonance imaging response with a single temporal model does not completely capture the full spectrum of neuronal dynamics. The use of electroencephalography regressors to model the response can increase confidence that the pharmacological magnetic resonance imaging is directly related to underlying neural activity.
Comparable studies
Other observational and cohort studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Taming the Ketamine Tiger Volunteers from a prison population | 2010 | Observational study | n = 20 |
| Increased spontaneous MEG signal diversity for psychoactive doses of ketamine, LSD and psilocybin Humans | 2017 | Observational study | |
| Disruption of Frontal–Parietal Communication by Ketamine, Propofol, and Sevoflurane Surgical patients undergoing induction of anesthesia with intravenous ketamine | 2013 | Observational cohort | n = 30 |
| Do the dissociative side effects of ketamine mediate its antidepressant effects? Treatment-resistant inpatients with major depressive disorder or bipolar disorder | 2014 | Observational cohort | n = 108 |
| Concomitant BDNF and sleep slow wave changes indicate ketamine-induced plasticity in major depressive disorder Patients with treatment-resistant major depressive disorder | 2012 | Observational cohort | n = 30 |
Citations in the library
Cited by 10
- Characterizing brain dynamics during ketamine-induced dissociation and subsequent interactions with propofol using human intracranial neurophysiology Nature Communications March 29, 2023
- The neurophysiology of ketamine: an integrative review Reviews in the Neurosciences May 5, 2020
- Effects of ketamine and midazolam on resting state connectivity and comparison with ENIGMA connectivity deficit patterns in schizophrenia Human Brain Mapping October 21, 2019
- Modulation of simultaneously collected hemodynamic and electrophysiological functional connectivity by ketamine and midazolam Human Brain Mapping December 6, 2019
- Neurophysiological correlates of ketamine-induced dissociative state in bipolar disorder: insights from real-world clinical settings. Molecular Psychiatry January 14, 2025
and 5 more in the library
Cites 5
- Disruption of Frontal–Parietal Communication by Ketamine, Propofol, and Sevoflurane Anesthesiology May 22, 2013
- Glutamate and the Neural Basis of the Subjective Effects of Ketamine Archives of General Psychiatry February 1, 2008
- Reviewing the ketamine model for schizophrenia Journal of Psychopharmacology November 20, 2013
- Evidence that Subanesthetic Doses of Ketamine Cause Sustained Disruptions of NMDA and AMPA-Mediated Frontoparietal Connectivity in Humans Journal of Neuroscience August 19, 2015
- Ketamine as a promising prototype for a new generation of rapid‐acting antidepressants Annals of the New York Academy of Sciences February 27, 2015