Pal Dinesh, Silverstein Brian H, Sharba Lana, Li Duan, Hambrecht-Wiedbusch Viviane S, Hudetz Anthony G, Mashour George A
Department of Anesthesiology, University of MichiganAnn Arbor, MI, United States.
Center for Consciousness Science, University of MichiganAnn Arbor, MI, United States.
Front Syst Neurosci. 2017 Jun 13;11:41. doi: 10.3389/fnsys.2017.00041. eCollection 2017.
Studies from human and non-human species have demonstrated a breakdown of functional corticocortical connectivity during general anesthesia induced by anesthetics with diverse molecular, neurophysiological, and pharmacological profiles. Recent studies have demonstrated that changes in long-range neural communication, and by corollary, functional connectivity, might be influenced by cross-frequency coupling (CFC) between the phase of slow oscillations and the amplitude of local fast oscillations. Phase-amplitude coupling (PAC) between slow oscillations and alpha rhythm during general anesthesia reveal distinct patterns depending on the anesthetic. In this study, we analyzed the effect of three clinically used anesthetics (propofol: = 6, sevoflurane: = 10, and ketamine: = 8) with distinct molecular mechanisms on changes in PAC in the frontal cortex of rat. The loss of righting reflex was used as a surrogate for unconsciousness. PAC was calculated using the modulation index (MI) algorithm between delta (1-4 Hz), theta (4-10 Hz), low gamma (25-55 Hz), and high gamma (65-125 Hz) bands. A linear mixed model with fixed effects was used for statistical comparisons between waking, anesthetized, and post-anesthesia recovery epochs. All three anesthetics increased the coupling between delta and low gamma ( < 0.0001) as well as between theta and low gamma ( < 0.0001) oscillations, which returned to baseline waking levels during the post-anesthetic recovery period. In addition, a reversible reduction in high gamma power ( < 0.0001) was a consistent change during anesthesia induced by all three agents. The changes in delta-high gamma and theta-high gamma PAC as well as power spectral changes in delta, theta, and low gamma bandwidths did not show a uniform response across the three anesthetics. These results encourage the study of alternative PAC patterns as drug-invariant markers of general anesthesia in humans.
来自人类和非人类物种的研究表明，在由具有不同分子、神经生理学和药理学特征的麻醉剂诱导的全身麻醉期间，功能性皮质-皮质连接性会出现破坏。最近的研究表明，远程神经通信的变化，以及相应地，功能连接性，可能会受到慢振荡相位与局部快振荡幅度之间的交叉频率耦合（CFC）的影响。全身麻醉期间慢振荡与α节律之间的相位-幅度耦合（PAC）根据麻醉剂的不同呈现出不同的模式。在本研究中，我们分析了三种具有不同分子机制的临床常用麻醉剂（丙泊酚：n = 6，七氟醚：n = 10，氯胺酮：n = 8）对大鼠额叶皮质PAC变化的影响。翻正反射消失被用作无意识状态的替代指标。使用调制指数（MI）算法计算δ（1 - 4 Hz）、θ（4 - 10 Hz）、低γ（25 - 55 Hz）和高γ（65 - 125 Hz）频段之间的PAC。使用具有固定效应的线性混合模型对清醒、麻醉和麻醉后恢复期进行统计比较。所有三种麻醉剂均增加了δ与低γ振荡之间（P < 0.0001）以及θ与低γ振荡之间（P < 0.0001）的耦合，这种耦合在麻醉后恢复期恢复到清醒时的基线水平。此外，所有三种药物诱导的麻醉期间，高γ功率的可逆性降低（P < 0.0001）是一个一致的变化。δ - 高γ和θ - 高γ PAC的变化以及δ、θ和低γ带宽的功率谱变化在三种麻醉剂之间并未表现出一致的反应。这些结果鼓励研究替代的PAC模式，作为人类全身麻醉的药物不变性标志物。
