Abnormal gamma-band oscillations (GBO) have been frequently associated with the pathophysiology of schizophrenia. GBO are modulated by glutamate, a neurotransmitter, which is continuously discussed to shape the complex symptom spectrum in schizophrenia. The current study examined the effects of ketamine, a glutamate N-methyl-D-aspartate receptor (NMDAR) antagonist, on the auditory-evoked gamma-band response (aeGBR) and psychopathological outcomes in healthy volunteers to investigate neuronal mechanisms of psychotic behavior. In a placebo-controlled, randomized crossover design, the aeGBR power, phase-locking factor (PLF) during a choice reaction task, the Positive and Negative Syndrome Scale (PANSS) and the Altered State of Consciousness (5D-ASC) Rating Scale were assessed in 25 healthy subjects. Ketamine was applied in a subanaesthetic dose. Low-resolution brain electromagnetic tomography was used for EEG source localization. Significant reductions of the aeGBR power and PLF were identified under ketamine administration compared to placebo (p < 0.01). Source-space analysis of aeGBR generators revealed significantly reduced current source density (CSD) within the anterior cingulate cortex during ketamine administration. Ketamine induced an increase in all PANSS (p < 0.001) as well as 5D-ASC scores (p < 0.01) and increased response times (p < 0.001) and error rates (p < 0.01). Only negative symptoms were significantly associated with an aeGBR power decrease (p = 0.033) as revealed by multiple linear regression. These findings argue for a substantial role of the glutamate system in the mediation of dysfunctional gamma band responses and negative symptomatology of schizophrenia and are compatible with the NMDAR hypofunction hypothesis of schizophrenia.

中文翻译：

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在亚麻醉氯胺酮下可降低听觉诱发的伽马带反应和精神分裂症样临床症状。

异常的γ波段振荡（GBO）经常与精神分裂症的病理生理相关。GBO由谷氨酸（一种神经递质）调节，对此进行了不断讨论以塑造精神分裂症的复杂症状谱。目前的研究检查了氯胺酮（一种谷氨酸N-甲基-D-天冬氨酸受体（NMDAR）拮抗剂）对健康志愿者的听觉诱发的γ波段反应（aeGBR）和心理病理结果的影响，以研究精神病行为的神经元机制。在安慰剂控制的随机分频设计中，选择反应任务期间的aeGBR功率，锁相因子（PLF），正负综合症量表（PANSS）和意识改变状态（5D-ASC）量表是在25位健康受试者中进行评估。氯胺酮以亚麻醉剂量施用。低分辨率脑电磁层析成像用于脑电图源定位。与安慰剂相比，氯胺酮给药后aeGBR功效和PLF明显降低（p <0.01）。对aeGBR发生器的源空间分析表明，在氯胺酮给药期间，前扣带回皮层内的电流源密度（CSD）显着降低。氯胺酮引起所有PANSS的增加（p <0.001）以及5D-ASC评分（p <0.01）的增加，响应时间（p <0.001）和错误率（p <0.01）的增加。多重线性回归显示，只有阴性症状与aeGBR功率降低显着相关（p = 0.033）。