Experimental and Clinical Research Center (ECRC), Dept. of Anesthesiology and Intensive Care Medicine, Charité - University Medicine Berlin, Germany.
Department of Psychiatry, Heinrich-Heine University, Düsseldorf, Germany.
Neuroimage Clin. 2018 Jun 1;19:745-757. doi: 10.1016/j.nicl.2018.05.037. eCollection 2018.
Subanesthetic dosages of the NMDAR antagonist, S-Ketamine, can cause changes in behavior in healthy subjects, which are similar to the state acute psychosis and are relevant in translational schizophrenia research. Functional magnetic resonance imaging (fMRI) can be used for non-hypothesis-driven analysis of brain connectivity. The correlation between clinical behavioral scores and neuroimaging can help to characterize ketamine effects on healthy brains in resting state.
seventeen healthy, male subjects (mean: 27.42 years, SD: 4.42) were administered an infusion with S-Ketamine (initial bolus 1 mg/kg and continuous infusion of 0.015625 mg/kg/min with dosage reduction -10%/10 min) or saline in a randomized, double-blind, cross-over study. During infusion, resting state connectivity was measured and analyzed with a seed-to-voxel fMRI analysis approach. The seed regions were located in the posterior cingulate cortex, intraparietal sulcus, dorsolateral prefrontal cortex and fronto-insular cortex. Receiver operating characteristics (ROC) were calculated to assess the accuracy of the ketamine-induced functional connectivity changes. Bivariate Pearson correlation was used for correlation testing of functional connectivity changes with changes of clinical scores (PANSS, 5D-ASC).
In the executive network (ECN), ketamine significantly increases the functional connectivity with parts of the anterior cingulum and superior frontal gyrus, but no significant correlations with clinical symptoms were found. Decreased connectivity between the salience network (SN) and the calcarine fissure was found, which is significantly correlated with negative symptoms (PANSS) (R2 > 0.4).
Decreased ketamine-induced functional connectivity in the salience network may qualify as accurate and highly predictive biomarkers for ketamine induced negative symptoms.
亚麻醉剂量的 NMDA 受体拮抗剂 S-氯胺酮可引起健康受试者的行为改变，这些改变类似于急性精神病状态，与转化精神分裂症研究相关。功能磁共振成像（fMRI）可用于对脑连接进行非假设驱动的分析。临床行为评分与神经影像学之间的相关性有助于在静息状态下描述氯胺酮对健康大脑的影响。
17 名健康男性受试者（平均年龄：27.42 岁，标准差：4.42）接受 S-氯胺酮（初始推注剂量为 1mg/kg，持续输注剂量为 0.015625mg/kg/min，剂量减少 10%/10min）或生理盐水的随机、双盲、交叉研究。在输注过程中，采用种子点到体素 fMRI 分析方法测量和分析静息状态下的连通性。种子区域位于后扣带回皮质、顶内沟、背外侧前额叶皮质和额岛叶皮质。计算接收者操作特征（ROC）以评估氯胺酮诱导的功能连通性变化的准确性。使用双变量 Pearson 相关检验功能连通性变化与临床评分（PANSS、5D-ASC）变化的相关性。
在执行网络（ECN）中，氯胺酮显著增加了与前扣带和额上回的部分区域的功能连通性，但与临床症状无显著相关性。发现突显网络（SN）与距状裂之间的连通性降低，与阴性症状（PANSS）显著相关（R2＞0.4）。
氯胺酮诱导的突显网络功能连通性降低可能是氯胺酮诱导的阴性症状的准确且高度预测性生物标志物。
