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 or a placebo to the same 24 healthy young adults at different times. While people rested, the team recorded brain activity with two methods at once: fMRI, which shows which brain areas are talking to each other, and EEG, which measures electrical brain waves. After ketamine, a key mid-frontal area showed weaker connections with the rest of the brain, while some parietal areas showed stronger connections. At the same time, EEG showed more slow brain waves (delta and theta) and more fast waves (gamma), which together suggested a drop in wakeful alertness. The pattern links ketamine’s changes in brain connections to changes in vigilance, and the authors say these brain measures might help explain or track how ketamine works in people, for example in studies of its antidepressant effects.

Key facts:

• The study tested about 24 healthy young adults in a randomized, double-blind crossover design, so each person received both ketamine and placebo at different visits without knowing which they got.
• The team recorded resting brain connectivity with fMRI and brain waves with EEG at the same time.
• After a low (subanesthetic) dose of S-ketamine, connectivity in the medial prefrontal cortex (a front brain area) decreased.
• At the same time, connectivity increased in intraparietal cortices (areas toward the top/back of the brain).
• EEG showed a shift toward more slow waves (delta and theta) and also more fast gamma activity after ketamine.
• Frontal (prefrontal) connectivity was negatively related to EEG gamma and theta activity, while parietal connectivity was positively related to EEG delta power.
• The authors conclude that ketamine’s changes in brain connectivity are directly tied to its effects on vigilance (wakeful alertness) measured by EEG, and they suggest these measures could be used as markers in future studies, for example about antidepressant effects.

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