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

View Article: PubMed Central - PubMed

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 placebo-controlled, 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.

No MeSH data available.


Related in: MedlinePlus

Mean (±SE) Clinician Administered Dissociative States Scale (CADSS) values for the rating scores for the placebo and ketamine conditions (n = 21).∗p < 0.05.
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Figure 1: Mean (±SE) Clinician Administered Dissociative States Scale (CADSS) values for the rating scores for the placebo and ketamine conditions (n = 21).∗p < 0.05.

Mentions: The mean (±SE) values for the rating scores for the placebo and ketamine conditions are displayed in Figure 1. Significant increased self-ratings for amnesia (WSRT = -2.83, df = 1/40, p < 0.005), depersonalization (WSRT = -3.53, df = 1/40, p < 0.0001), and derealisation symptoms (WSRT = -3.36, df = 1/40, p < 0.01) were shown for the ketamine compared to placebo infusion condition. Ketamine also increased the observer rated symptom scores (WSRT = -3.72, df = 1/40, p < 0.0001) relative to placebo.


Effects of Ketamine on Resting-State EEG Activity and Their Relationship to Perceptual/Dissociative Symptoms in Healthy Humans
Mean (±SE) Clinician Administered Dissociative States Scale (CADSS) values for the rating scores for the placebo and ketamine conditions (n = 21).∗p < 0.05.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5037139&req=5

Figure 1: Mean (±SE) Clinician Administered Dissociative States Scale (CADSS) values for the rating scores for the placebo and ketamine conditions (n = 21).∗p < 0.05.
Mentions: The mean (±SE) values for the rating scores for the placebo and ketamine conditions are displayed in Figure 1. Significant increased self-ratings for amnesia (WSRT = -2.83, df = 1/40, p < 0.005), depersonalization (WSRT = -3.53, df = 1/40, p < 0.0001), and derealisation symptoms (WSRT = -3.36, df = 1/40, p < 0.01) were shown for the ketamine compared to placebo infusion condition. Ketamine also increased the observer rated symptom scores (WSRT = -3.72, df = 1/40, p < 0.0001) relative to placebo.

View Article: PubMed Central - PubMed

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 placebo-controlled, 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.

No MeSH data available.


Related in: MedlinePlus