Acute ketamine dysregulates task-related gamma-band oscillations in thalamo-cortical circuits in schizophrenia.
Acute ketamine dysregulates task-related gamma-band oscillations in thalamo-cortical circuits in schizophrenia.
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急性氯胺酮会使精神分裂症患者丘脑-皮层回路中与任务相关的伽马波段振荡失调。
DOI：
10.1093/brain/awy175
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发表时间：
2018-08-01
期刊：
影响因子：
--
通讯作者：
Uhlhaas PJ
中科院分区：
文献类型：
--
作者：
Grent-'t-Jong T;Rivolta D;Gross J;Gajwani R;Lawrie SM;Schwannauer M;Heidegger T;Wibral M;Singer W;Sauer A;Scheller B;Uhlhaas PJ
NMDA 受体缺陷与精神分裂症有关。格伦特·琼等人。研究表明，用氯胺酮治疗健康对照会引发视觉处理过程中神经振荡的变化，这与精神分裂症患者所见的变化不同。这表明急性 NMDA 受体功能低下并不能解释该疾病的视觉感知缺陷。 N-甲基-d-天冬氨酸受体（NMDAR）功能减退被认为是精神分裂症认知缺陷和神经元动力学异常的潜在机制。为了检验这一假设，我们首先以单盲交叉设计的方式对 14 名参与者施用亚麻醉剂量的 S-氯胺酮 (0.006 mg/kg/min) 或生理盐水，同时在视觉任务期间记录脑磁图数据。此外，在未接受药物治疗的首发精神病患者 (n = 10) 和慢性精神分裂症患者 (n = 16) 样本中获得了脑磁图数据，以便比较临床人群的神经元动态与 NMDAR 功能减退的情况。脑磁图数据在枕叶和丘脑感兴趣区域的 1-90 Hz 频率范围内进行源级分析。此外，使用格兰杰因果关系进行定向功能连接分析，并使用定向不对称指数研究反馈和前馈活动。使用阳性和阴性综合症量表对精神病理学进行评估。健康志愿者的急性氯胺酮给药对认知和精神病理学产生了与首发和慢性精神分裂症患者相似的影响。然而，氯胺酮对高频振荡及其连接分布的影响与这些观察结果不一致。氯胺酮增加枕骨区域伽马功率（63-80 Hz）的幅度和频率，并上调低频（5-28 Hz）活动。此外，氯胺酮扰乱了高频和低频的前馈和反馈信号，导致丘脑皮质网络的连接性低下和过度。相比之下，首发和慢性精神分裂症患者表现出不同的脑磁图活动模式，其特征是任务引起的高伽马带振荡减少，前馈/反馈介导的格兰杰因果连接性显着增加。因此，目前的数据对该疾病的认知功能障碍和回路损伤的理论具有影响，表明急性 NMDAR 功能减退不会重现精神分裂症中观察到的视觉处理过程中神经振荡的改变。
NMDA receptor deficits have been implicated in schizophrenia. Grent-’t-Jong et al. show that treating healthy controls with ketamine triggers changes in neural oscillations during visual processing distinct from those seen in patients with schizophrenia. This suggests that acute NMDA receptor hypofunction does not account for visuo-perceptual deficits in the disorder. Hypofunction of the N-methyl-d-aspartate receptor (NMDAR) has been implicated as a possible mechanism underlying cognitive deficits and aberrant neuronal dynamics in schizophrenia. To test this hypothesis, we first administered a sub-anaesthetic dose of S-ketamine (0.006 mg/kg/min) or saline in a single-blind crossover design in 14 participants while magnetoencephalographic data were recorded during a visual task. In addition, magnetoencephalographic data were obtained in a sample of unmedicated first-episode psychosis patients (n = 10) and in patients with chronic schizophrenia (n = 16) to allow for comparisons of neuronal dynamics in clinical populations versus NMDAR hypofunctioning. Magnetoencephalographic data were analysed at source-level in the 1–90 Hz frequency range in occipital and thalamic regions of interest. In addition, directed functional connectivity analysis was performed using Granger causality and feedback and feedforward activity was investigated using a directed asymmetry index. Psychopathology was assessed with the Positive and Negative Syndrome Scale. Acute ketamine administration in healthy volunteers led to similar effects on cognition and psychopathology as observed in first-episode and chronic schizophrenia patients. However, the effects of ketamine on high-frequency oscillations and their connectivity profile were not consistent with these observations. Ketamine increased amplitude and frequency of gamma-power (63–80 Hz) in occipital regions and upregulated low frequency (5–28 Hz) activity. Moreover, ketamine disrupted feedforward and feedback signalling at high and low frequencies leading to hypo- and hyper-connectivity in thalamo-cortical networks. In contrast, first-episode and chronic schizophrenia patients showed a different pattern of magnetoencephalographic activity, characterized by decreased task-induced high-gamma band oscillations and predominantly increased feedforward/feedback-mediated Granger causality connectivity. Accordingly, the current data have implications for theories of cognitive dysfunctions and circuit impairments in the disorder, suggesting that acute NMDAR hypofunction does not recreate alterations in neural oscillations during visual processing observed in schizophrenia.
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影响因子：
3.7
作者：
Hakami T;Jones NC;Tolmacheva EA;Gaudias J;Chaumont J;Salzberg M;O'Brien TJ;Pinault D
通讯作者：
Pinault D
影响因子：
16.2
作者：
Fries P
通讯作者：
Fries P
影响因子：
25.8
作者：
Hirano Y;Oribe N;Kanba S;Onitsuka T;Nestor PG;Spencer KM
通讯作者：
Spencer KM
影响因子：
3.3
作者：
Ehrlichman, R. S.;Gandal, M. J.;Siegel, S. J.
通讯作者：
Siegel, S. J.
影响因子：
64.8
作者：
COBB, SR;BUHL, EH;SOMOGYI, P
通讯作者：
SOMOGYI, P