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

Summary & key facts

This randomized, double-blind, placebo-controlled crossover study gave subanesthetic S‑ketamine to 24 healthy young people while recording fMRI and EEG at rest. After ketamine, fMRI showed less connectivity in the medial prefrontal cortex and more connectivity in left and right intraparietal (parietal) areas of the default mode network. EEG showed more power in slow waves (delta and theta) and in fast gamma waves. The authors report links between these EEG changes and the fMRI connectivity changes and suggest the results relate to a ketamine-induced drop in vigilance.

Key facts:

• Study type: randomized, double-blind, placebo-controlled crossover with simultaneous resting-state fMRI and EEG in N = 24 healthy young subjects.
• Ketamine dose: S‑Ketamine given as a 0.1 mg/kg bolus over 5 minutes, then 0.015625 mg/kg/min infusion (up to 1 hour); the resting fMRI started 34 minutes after infusion began.
• fMRI finding: ketamine reduced functional connectivity in the medial prefrontal cortex (mPFC) of the default mode network and increased connectivity in left and right intraparietal cortices (IPL).
• EEG finding: ketamine shifted EEG power toward slow bands (delta 0.53–4 Hz and theta 4–8 Hz) and toward fast gamma (30–50 Hz); alpha (8–12 Hz) and beta (12–25 Hz) showed no consistent changes.
• Relationships: frontal (mPFC) connectivity was negatively related to EEG gamma and theta activity, while parietal connectivity was positively related to EEG delta power, according to the authors' analyses.
• Authors' interpretation: the paper suggests a direct relationship between ketamine-induced fMRI connectivity changes and a concomitant decrease in vigilance measured by EEG, and notes these functional changes might be useful as surrogate en

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)