Dynamic reconfiguration of frequency-specific cortical coactivation patterns during psychedelic and anaesthetized states induced by ketamine

This open-label study (n=15) assessed the dynamic organization of spontaneous cortical activity during wakefulness, and during altered consciousness induced by both subanaesthetic and anaesthetic doses of ketamine, which are associated with psychedelic effects. Using EEG, it was found that anaesthetic doses of ketamine tend to shift the configuration toward brain states with low spatial variability while subanesthetic ketamine was associated with a richer repertoire of spatially distributed patterns of brain activity. These findings present a novel description of ketamine’s modulation of cortical activity.

Abstract

“Recent neuroimaging studies have demonstrated that spontaneous brain activity exhibits a rich spatiotemporal structure that can be characterized as the exploration of a repertoire of spatially distributed patterns that recur over time. The repertoire of brain states may reflect the capacity for consciousness since general anaesthetics suppress and psychedelic drugs enhance such dynamics. However, the modulation of brain activity repertoire across varying states of consciousness has not yet been studied in a systematic and unified framework. As a unique drug that has both psychedelic and anaesthetic properties depending on the dose, ketamine offers an opportunity to examine the brain reconfiguration dynamics along the continuum of consciousness from anaesthetized to psychedelic states. Here we investigated the dynamic organization of cortical activity during wakefulness and during altered states of consciousness induced by different doses of ketamine. Through k-means clustering analysis on the envelope data of source-localized electroencephalographic (EEG) signals, we identified a set of recurring states that represent frequency-specific spatial coactivation patterns. We quantified the effect of ketamine on individual brain states in terms of fractional occupancy and transition probabilities and found that ketamine anaesthesia tends to shift the configuration toward brain states with low spatial variability. Furthermore, by assessing the temporal dynamics of the occurrence and transitions of brain states, we showed that subanesthetic ketamine is associated with a richer repertoire, while anaesthetic ketamine induces dynamic changes in brain state organization, with the repertoire richness evolving from a reduced level to one comparable to that during normal wakefulness before recovery of consciousness. These results provide a novel description of ketamine’s modulation of the dynamic configuration of cortical activity and advance understanding of the neurophysiological mechanism of ketamine in terms of the spatial, temporal, and spectral structures of underlying whole-brain dynamics.”

Authors: Duan Li, Phillip E. Vlisides & George A. Mashour

Summary of Dynamic reconfiguration of frequency-specific cortical coactivation patterns during psychedelic and anaesthetized states induced by ketamine

Introduction

Ketamine is thought to work primarily by antagonizing N-methyl-D-aspartate receptors and HCN1 channels, and has psychedelic and anesthetic properties in a dose-dependent manner. Ketamine has been demonstrated to induce frequency-specific changes in electrophysiological oscillatory activity and network-specific changes in hemodynamic responses. However, time-averaged electrophysiological or functional magnetic resonance imaging data that span at least a few minutes disregards the vast amount of time-varying information that is present in the data.

The resting brain is an inherently dynamic system, and its activity exhibits rich spatiotemporal structure. These dynamics may be a manifestation of covert cognitive information processing, and reflect the information capacity of the brain that is thought to be central to consciousness. General anesthetics such as propofol, ketamine, sevoflurane, and isoflurane suppress the flexible brain configurations during wakefulness to a rigid brain configuration that is predominantly shaped by brain anatomy. However, psychedelic drugs typically induce an expanded repertoire of brain states.

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