Effects of Ketamine on Resting-State EEG Activity and Their Relationship to Perceptual/Dissociative Symptoms in Healthy Humans

Abstract

N-methyl-D-aspartate (NMDA) receptor antagonists administered to healthy humans results in schizophrenia-like symptoms, which preclinical research suggests are due to glutamatergically altered brain oscillations. Here, we examined resting-state electroencephalographic activity in 21 healthy volunteers assessed in a placebocontrolled, double-blind, randomized study involving administration of either a saline infusion or a sub-anesthetic dose of ketamine, an NMDA receptor antagonist. Frequency-specific current source density (CSD) was assessed at sensor-level and source-level using eLORETA within regions of interest of a triple network model of schizophrenia (this model posits a dysfunctional switching between large-scale Default Mode and Central Executive networks by the monitor-controlling Salience Network). These CSDs were measured in each session along with subjective symptoms as indexed with the Clinician Administered Dissociative States Scale. Ketamine-induced CSD reductions in slow (delta/theta and alpha) and increases in fast (gamma) frequencies at scalp electrode sites were paralleled by frequency-specific CSD changes in the Default Mode, Central Executive, and Salience networks. Subjective symptoms scores were increased with ketamine and ratings of depersonalization in particular were associated with alpha CSD reductions in general and in specific regions of interest in each of the three networks. These results tentatively support the hypothesis that pathological brain oscillations associated with hypofunctional NMDA receptor activity may contribute to the emergence of the perceptual/dissociate symptoms of schizophrenia.

Hallucinogen Persisting Perception Disorder Following Therapeutic Ketamine: A Case Report

“…Consistent in both animal and human studies, however, is the observation that ketamine increases activity of brain waves in the gamma (30 to 60 Hz) range. De la Salle et al reported such an increase in gamma current density in the default mode network implicated in schizophrenia, as well as activation of gamma frequencies across the cerebrum [12]. This finding supports a disinhibition model of HPPD.…”

Unsuccessful reduction of high‐frequency alpha activity during cognitive activation in schizophrenia

“…This is evidenced by the effect of NMDA receptor blockade on alpha activity in humans. 67 The hypofunction of the NMDA receptors in SCZ is known as cortical hyper-excitation by disinhibitory pyramidal neurons. 68 Improved cognitive performance is indexed by increased upper alpha power (individual alpha frequency, 8-10 Hz [AE2 Hz]) at the pre-stimulus interval in humans.…”

Aberrant Network Activity in Schizophrenia

“…Further studies add to the confusion by demonstrating that some patients demonstrate increased gamma oscillations and associated connectivity [14–16]. In addition, measurement of gamma rhythms in patients with specific polymorphisms associated with schizophrenia revealed that most correlated with elevated, rather than reduced, gamma power [17].…”

“…However, the literature is again equivocal. Decreases in delta rhythm power and coherence have been reported [14,32,33] almost as frequently as elevations [34–36]. Observations of wake-state theta activity are similarly mixed.…”