Department of Anesthesiology, Medical College of Wisconsin, USA.
Neuroimage. 2013 Dec;83:581-92. doi: 10.1016/j.neuroimage.2013.07.003. Epub 2013 Jul 10.
The dose-dependent effects of anesthetics on brain functional connectivity are incompletely understood. Resting-state functional magnetic resonance imaging (rsfMRI) is widely used to assess the functional connectivity in humans and animals. Propofol is an anesthetic agent with desirable characteristics for functional neuroimaging in animals but its dose-dependent effects on rsfMRI functional connectivity have not been determined. Here we tested the hypothesis that brain functional connectivity undergoes specific changes in distinct neural networks at anesthetic depths associated with loss of consciousness. We acquired spontaneous blood oxygen level-dependent (BOLD) signals simultaneously with electroencephalographic (EEG) signals from rats under steady-state, intravenously administered propofol at increasing doses from light sedation to deep anesthesia (20, 40, 60, 80, and 100 mg/kg/h IV). Power spectra and burst suppression ratio were calculated from the EEG to verify anesthetic depth. Functional connectivity was determined from the whole brain correlation of BOLD data in regions of interest followed by a segmentation of the correlation maps into anatomically defined regional connectivity. We found that propofol produced multiphasic, dose dependent changes in functional connectivity of various cortical and subcortical networks. Cluster analysis predicted segregation of connectivity into two cortical and two subcortical clusters. In one cortical cluster (somatosensory and parietal), the early reduction in connectivity was followed by transient reversal; in the other cluster (sensory, motor and cingulate/retrosplenial), this rebound was absent. The connectivity of the subcortical cluster (brainstem, hippocampal and caudate) was strongly reduced, whereas that of another (hypothalamus, medial thalamus and n. basalis) did not. Subcortical connectivity increased again in deep anesthesia associated with EEG burst suppression. Regional correlation analysis confirmed the breakdown of connectivity within and between specific cortical and subcortical networks with deepening propofol anesthesia. Cortical connectivity was suppressed before subcortical connectivity at a critical propofol dose associated with loss of consciousness.
麻醉对脑功能连接的剂量依赖性影响尚不完全清楚。静息态功能磁共振成像（rsfMRI）广泛用于评估人和动物的功能连接。异丙酚是一种具有理想特性的麻醉剂，可用于动物的功能神经影像学，但尚未确定其对 rsfMRI 功能连接的剂量依赖性影响。在这里，我们假设在与意识丧失相关的麻醉深度下，脑功能连接会在不同的神经网络中发生特定的变化。我们从大鼠获取了在静脉内给予异丙酚的稳定状态下同时采集的自发血氧水平依赖（BOLD）信号和脑电图（EEG）信号，异丙酚的剂量从轻度镇静到深度麻醉（20、40、60、80 和 100 mg/kg/h IV）逐渐增加。从 EEG 中计算功率谱和爆发抑制比以验证麻醉深度。从感兴趣区域的 BOLD 数据的整体大脑相关性确定功能连接，然后将相关性图分割成解剖定义的区域连接。我们发现，异丙酚在各种皮质和皮质下网络的功能连接中产生了多相、剂量依赖性的变化。聚类分析预测了连接性的分类为两个皮质和两个皮质下聚类。在一个皮质聚类（感觉和顶叶）中，连接性的早期减少随后是短暂的逆转；在另一个聚类（感觉、运动和扣带回/后扣带回）中，这种反弹不存在。皮质下聚类（脑干、海马体和尾状核）的连接性强烈降低，而另一个聚类（下丘脑、内侧丘脑和基底核）的连接性没有降低。与 EEG 爆发抑制相关的深度麻醉下，皮质下连接再次增加。区域相关性分析证实了在加深异丙酚麻醉时特定皮质和皮质下网络内和之间的连接性中断。皮质连接在与意识丧失相关的临界异丙酚剂量下在皮质下连接之前被抑制。
