Ketamine effects on default mode network activity and vigilance: A randomized, placebo‐controlled crossover simultaneous fMRI/EEG study

Summary & key facts

Researchers gave a low, non-anesthetic dose of S‑ketamine and a placebo to the same 24 healthy young people in a study where neither the participants nor the experimenters knew which treatment was given. While the people rested, the team recorded brain activity with two methods at the same time: fMRI, which images blood flow in the brain, and EEG, which records electrical brain waves. After ketamine, parts of the frontal brain showed weaker connections while parts of the parietal brain showed stronger connections. At the same time, the EEG showed more slow waves (delta and theta) and more fast waves (gamma), which together point to a drop in vigilance or alertness. The study suggests these brain-imaging changes and the drop in alertness happened together, and the pattern might help explain how ketamine can act quickly against depression, but the results are from healthy people and don’t prove how ketamine works in patients.

Key facts:

• The study tested 24 healthy young people. Each person received both a low (non-anesthetic) dose of S‑ketamine and a placebo in different sessions, and neither the people nor the researchers knew which one was given at the time.
• The researchers recorded resting brain activity with fMRI (which measures blood flow) and EEG (which measures electrical brain waves) at the same time.
• After ketamine, functional connections in the medial prefrontal cortex (a front part of the brain) were weaker than after placebo.
• Ketamine increased functional connectivity in intraparietal cortices (areas toward the top-back of the brain).
• EEG showed a shift of energy to slower waves (delta and theta) and also to faster gamma waves after ketamine, a pattern the authors link to lowered vigilance or alertness.
• Frontal connectivity was lower when theta and gamma activity were higher, while parietal connectivity tended to be higher when delta power was stronger, suggesting a direct link between the EEG signs of lowered vigilance and the fMRI connectivity changes; the authors say this could provide a brain-based framework for ketamine’s fast antidepressant effects, but it is not proof of how treatment works in patients.

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).

Topics

Functional Brain Connectivity Studies Neural and Behavioral Psychology Studies Treatment of Major Depression

Categories

Cognitive Neuroscience Life Sciences Neuroscience

Tags

Audiology Brain activity and meditation Cognition Default mode network EEG-fMRI Electroencephalography Functional magnetic resonance imaging Ketamine Medicine Neuroscience Prefrontal cortex Psychology Resting state fMRI Task-positive network Vigilance (psychology)

Substances

Ketamine

Conditions & symptoms

Depression Difficulty focusing