Ketamine effects on default mode network activity and vigilance: A randomized, placebo‐controlled crossover simultaneous fMRI/EEG study
Norman Zacharias, Francesco Musso, Felix Müller, Florian Lammers, Andreas Saleh, Markus K. London, Peter de Boer, Georg Winterer
Human Brain Mapping September 18, 2019 DOI: 10.1002/hbm.24791 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized, double-blind, placebo-controlled crossover study Peer reviewed |
|---|---|
| Sample size | 24 |
| Population | Healthy young subjects |
| Intervention | subanesthetic S-Ketamine |
| Dose | subanesthetic |
| Topics | Default mode network Ketamine Esketamine |
| Keywords | Vigilance psychology Electroencephalography Resting State FMRI Prefrontal cortex EEG-FMRI Task-positive network Audiology Cognition |
| Citations | 70 |
| Key points | Ketamine-induced decreases in medial prefrontal functional connectivity are directly related to diminished vigilance as assessed by EEG. |
Abstract
In resting-state functional connectivity experiments, a steady state (of consciousness) is commonly supposed. However, recent research has shown that the resting state is a rather dynamic than a steady state. In particular, changes of vigilance appear to play a prominent role. Accordingly, it is critical to assess the state of vigilance when conducting pharmacodynamic studies with resting-state functional magnetic resonance imaging (fMRI) using drugs that are known to affect vigilance such as (subanesthetic) ketamine. In this study, we sought to clarify whether the previously described ketamine-induced prefrontal decrease of functional connectivity is related to diminished vigilance as assessed by electroencephalography (EEG). We conducted a randomized, double-blind, placebo-controlled crossover study with subanesthetic S-Ketamine in N = 24 healthy, young subjects by simultaneous acquisition of resting-state fMRI and EEG data. We conducted seed-based default mode network functional connectivity and EEG power spectrum analyses. After ketamine administration, decreased functional connectivity was found in medial prefrontal cortex whereas increased connectivities were observed in intraparietal cortices. In EEG, a shift of energy to slow (delta, theta) and fast (gamma) wave frequencies was seen in the ketamine condition. Frontal connectivity is negatively related to EEG gamma and theta activity while a positive relationship is found for parietal connectivity and EEG delta power. Our results suggest a direct relationship between ketamine-induced functional connectivity changes and the concomitant decrease of vigilance in EEG. The observed functional changes after ketamine administration may serve as surrogate end points and provide a neurophysiological framework, for example, for the antidepressant action of ketamine (trial name: 29JN1556, EudraCT Number: 2009-012399-28).
Comparable studies
Other randomized controlled trials on default mode network, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin Healthy volunteers | 2012 | Within-subjects, placebo-controlled, task-free fMRI study | n = 30 |
| The effects of psilocybin and MDMA on between-network resting state functional connectivity in healthy volunteers | 2014 | Placebo-controlled study | |
| Ketamine Decreases Resting State Functional Network Connectivity in Healthy Subjects: Implications for Antidepressant Drug Action Healthy subjects | 2012 | Randomized, placebo-controlled, double-blind, crossover rsfMRI challenge | |
| Antidepressants Normalize the Default Mode Network in Patients With Dysthymia Subjects with dysthymic disorder and healthy control participants aged 18 to 53 years | 2013 | Randomized controlled trial | n = 41 |
| Functional Connectivity Measures After Psilocybin Inform a Novel Hypothesis of Early Psychosis Healthy volunteers | 2012 | Within-subject, placebo-controlled experimental study | n = 15 |
Citations in the library
Cited by 44
- Ketamine and Serotonergic Psychedelics: Common Mechanisms Underlying the Effects of Rapid-Acting Antidepressants The International Journal of Neuropsychopharmacology November 16, 2020
- The anterior cingulate cortex as a key locus of ketamine’s antidepressant action Neuroscience & Biobehavioral Reviews May 10, 2021
- The Psychedelic Future of Post-Traumatic Stress Disorder Treatment Current Neuropharmacology January 5, 2024
- A unified model of ketamine's dissociative and psychedelic properties. Journal of Psychopharmacology December 17, 2022
- The Relationship Between Acute Dissociative Effects Induced by Ketamine and Treatment Response in Adolescent Patients with Treatment-Resistant Depression Journal of Child and Adolescent Psychopharmacology February 1, 2023
and 39 more in the library
Cites 11
- Functional connectivity of default mode network components: Correlation, anticorrelation, and causality Human Brain Mapping January 24, 2008
- Ketamine-Induced Deficits in Auditory and Visual Context-Dependent Processing in Healthy Volunteers Archives of General Psychiatry December 1, 2000
- Ketamine Decreases Resting State Functional Network Connectivity in Healthy Subjects: Implications for Antidepressant Drug Action PLoS One September 24, 2012
- Concomitant BDNF and sleep slow wave changes indicate ketamine-induced plasticity in major depressive disorder The International Journal of Neuropsychopharmacology June 7, 2012
- Evidence that Subanesthetic Doses of Ketamine Cause Sustained Disruptions of NMDA and AMPA-Mediated Frontoparietal Connectivity in Humans Journal of Neuroscience August 19, 2015
and 6 more in the library