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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.


Scatterplots of significant ketamine-induced changes in scalp and source-localized EEG and changes in CADSS scores induced by ketamine (n = 21). Scalp CSD scatterplots represent averaged values of significant regional changes.
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Figure 6: Scatterplots of significant ketamine-induced changes in scalp and source-localized EEG and changes in CADSS scores induced by ketamine (n = 21). Scalp CSD scatterplots represent averaged values of significant regional changes.

Mentions: Changes in symptoms induced by ketamine were significantly associated with ketamine-induced changes in scalp and source-localized EEG, but only with alpha CSD (Figure 6). Scalp EEG alpha changes were negatively correlated with depersonalization ratings (r = -0.58, p < 0.006). For source-localized EEG, reductions in alpha CSD in the left (r = -0.66, p < 0.04) and right (r = -0.64, p < 0.002) PCC hemispheres of the DMN, and the right PPC (r = -0.54, p < 0.01) and AI hemispheres (r = -0.45, p < 0.04) of the CEN and SN, respectively, were related to increased depersonalization rating scores. No other correlations were evidences with delta, theta, beta, or gamma rhythms.


Effects of Ketamine on Resting-State EEG Activity and Their Relationship to Perceptual/Dissociative Symptoms in Healthy Humans
Scatterplots of significant ketamine-induced changes in scalp and source-localized EEG and changes in CADSS scores induced by ketamine (n = 21). Scalp CSD scatterplots represent averaged values of significant regional changes.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 6: Scatterplots of significant ketamine-induced changes in scalp and source-localized EEG and changes in CADSS scores induced by ketamine (n = 21). Scalp CSD scatterplots represent averaged values of significant regional changes.
Mentions: Changes in symptoms induced by ketamine were significantly associated with ketamine-induced changes in scalp and source-localized EEG, but only with alpha CSD (Figure 6). Scalp EEG alpha changes were negatively correlated with depersonalization ratings (r = -0.58, p < 0.006). For source-localized EEG, reductions in alpha CSD in the left (r = -0.66, p < 0.04) and right (r = -0.64, p < 0.002) PCC hemispheres of the DMN, and the right PPC (r = -0.54, p < 0.01) and AI hemispheres (r = -0.45, p < 0.04) of the CEN and SN, respectively, were related to increased depersonalization rating scores. No other correlations were evidences with delta, theta, beta, or gamma rhythms.

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.