Department of Anesthesiology, Leiden University Medical Center, Leiden, The Netherlands.
Anesthesiology. 2012 Oct;117(4):868-77. doi: 10.1097/ALN.0b013e31826a0db3.
The influence of psychoactive drugs on the central nervous system has been investigated with positron emission tomography and task-related functional magnetic resonance imaging. However, it is not known how these drugs affect the intrinsic large-scale interactions of the brain (resting-state functional magnetic resonance imaging connectivity). In this study, the effect of low-dose S(+)-ketamine on intrinsic brain connectivity was investigated.
Twelve healthy, male volunteers received a 2-h intravenous S(+)-ketamine infusion (first hour 20 mg/70 kg, second hour 40 mg/70 kg). Before, during, and after S(+)-ketamine administration, resting-state brain connectivity was measured. In addition, heat pain tests were performed between imaging sessions to determine ketamine-induced analgesia. A mixed-effects general linear model was used to determine drug and pain effects on resting-state brain connectivity.
Ketamine increased the connectivity most importantly in the cerebellum and visual cortex in relation to the medial visual network. A decrease in connectivity was observed in the auditory and somatosensory network in relation to regions responsible for pain sensing and the affective processing of pain, which included the amygdala, insula, and anterior cingulate cortex. Connectivity variations related to fluctuations in pain scores were observed in the anterior cingulate cortex, insula, orbitofrontal cortex, and the brainstem, regions involved in descending inhibition of pain.
Changes in connectivity were observed in the areas that explain ketamine's pharmacodynamic profile with respect to analgesia and psychedelic and other side effects. In addition, pain and ketamine changed brain connectivity in areas involved in endogenous pain modulation.
正电子发射断层扫描和任务相关功能磁共振成像已经研究了精神活性药物对中枢神经系统的影响。然而，目前尚不清楚这些药物如何影响大脑的固有大规模相互作用（静息状态功能磁共振成像连接）。在这项研究中，研究了低剂量 S(+)-氯胺酮对内在大脑连接的影响。
12 名健康男性志愿者接受了 2 小时静脉 S(+)-氯胺酮输注（第 1 小时 20mg/70kg，第 2 小时 40mg/70kg）。在 S(+)-氯胺酮给药前、给药中和给药后测量静息状态大脑连接。此外，在成像期间之间进行热痛测试，以确定氯胺酮引起的镇痛作用。使用混合效应广义线性模型来确定药物和疼痛对静息状态大脑连接的影响。
氯胺酮增加了与内侧视觉网络相关的小脑和视觉皮层的连接最重要。与负责疼痛感知和疼痛的情感处理的区域（包括杏仁核、岛叶和前扣带皮层）相关的听觉和躯体感觉网络的连接减少。与疼痛评分波动相关的连接变化在前扣带皮层、岛叶、眶额皮质和脑干中观察到，这些区域参与疼痛的下行抑制。
在解释氯胺酮在镇痛和迷幻作用以及其他副作用方面的药效学特征的区域观察到连接的变化。此外，疼痛和氯胺酮改变了参与内源性疼痛调节的区域的大脑连接。
