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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

Grand averaged scalp current source density (CSD) topographic maps for the placebo and ketamine conditions for the frequency bands, together with a spectral graph of gamma from the Cz site.
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Figure 2: Grand averaged scalp current source density (CSD) topographic maps for the placebo and ketamine conditions for the frequency bands, together with a spectral graph of gamma from the Cz site.

Mentions: As shown in Figure 2, scalp analyzed current density values for slow and fast oscillations were significantly influenced by ketamine. Delta exhibited significant treatment (F = 6.14, df = 1/20, p < 0.02) and treatment × region interaction effects (F = 3.52, df = 2/40, p < 0.04), with ketamine acting to reduce CSD bilaterally in temporal-central (p < 0.02) and posterior (p < 0.01) regions. Within a treatment region × laterality interaction (F = 3.77, df = 4/80, p < 0.007), theta CSD was similarly reduced in the left (p < 0.04) and right (p < 0.03) posterior cortex. Exhibiting treatment (F = 9.91, df = 1/40, p < 0.005), treatment x region (F = 4.43, df = 2/40, p < 0.02) and treatment × region × laterality interaction effects (F = 4.35, df = 4/80, p < 0.003), alpha current density was significantly diminished in left (p < 0.002) and right (p < 0.01) anterior, middle (p < 0.006) and right (p < 0.004) temporal-central, and posterior regions following ketamine infusion. Beta current density was not affected by ketamine treatment but significant treatment effects for gamma (F = 5.49, df = 1/20, p < 0.03) showed that ketamine increased current density of these oscillations across all scalp regions. Table 1 displays a summary of the regional effects of ketamine vs. placebo.


Effects of Ketamine on Resting-State EEG Activity and Their Relationship to Perceptual/Dissociative Symptoms in Healthy Humans
Grand averaged scalp current source density (CSD) topographic maps for the placebo and ketamine conditions for the frequency bands, together with a spectral graph of gamma from the Cz site.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 2: Grand averaged scalp current source density (CSD) topographic maps for the placebo and ketamine conditions for the frequency bands, together with a spectral graph of gamma from the Cz site.
Mentions: As shown in Figure 2, scalp analyzed current density values for slow and fast oscillations were significantly influenced by ketamine. Delta exhibited significant treatment (F = 6.14, df = 1/20, p < 0.02) and treatment × region interaction effects (F = 3.52, df = 2/40, p < 0.04), with ketamine acting to reduce CSD bilaterally in temporal-central (p < 0.02) and posterior (p < 0.01) regions. Within a treatment region × laterality interaction (F = 3.77, df = 4/80, p < 0.007), theta CSD was similarly reduced in the left (p < 0.04) and right (p < 0.03) posterior cortex. Exhibiting treatment (F = 9.91, df = 1/40, p < 0.005), treatment x region (F = 4.43, df = 2/40, p < 0.02) and treatment × region × laterality interaction effects (F = 4.35, df = 4/80, p < 0.003), alpha current density was significantly diminished in left (p < 0.002) and right (p < 0.01) anterior, middle (p < 0.006) and right (p < 0.004) temporal-central, and posterior regions following ketamine infusion. Beta current density was not affected by ketamine treatment but significant treatment effects for gamma (F = 5.49, df = 1/20, p < 0.03) showed that ketamine increased current density of these oscillations across all scalp regions. Table 1 displays a summary of the regional effects of ketamine vs. 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