GABAA circuit mechanisms are associated with ether anesthesia-induced unconsciousness

Abstract

Objective An emerging paradigm for understanding how anesthetics induce altered arousal is relating receptor targeting in specific neural circuits to electroencephalogram (EEG) activity. We have previously found that enhanced gamma amino-butyric acid A (GABAA) inhibitory post-synaptic currents (IPSCs) manifest with large-amplitude slow (0.1–1 Hz) and frontally coherent alpha (8–12 Hz) oscillations. Therefore, we investigated the EEG signatures of modern day derivatives of ether (MDDE) to assess the extent to which we could obtain insights into MDDE anesthetic mechanisms Methods We retrospectively studied cases from our database in which patients received isoflurane vs. isoflurane/ketamine (n=10 each) or desflurane vs. desflurane/ketamine (n = 9 each). We analyzed the EEG recordings with spectral power and coherence methods. Results Similar to known GABAA circuit level mechanisms, we found that MDDE induced large amplitude slow and frontally coherent alpha oscillations. Additionally, MDDE also induced frontally coherent theta (4–8 Hz) oscillations. Reduction of GABAergic IPSCs with ketamine resulted in beta/gamma (13–40 Hz) oscillations, and significantly reduced MDDE-induced slow, theta and alpha oscillation power. Conclusions MDDE are associated with large amplitude slow oscillations and coherent alpha and theta oscillations. Significance These observations are consistent with the notion that GABAA circuit-level mechanisms are associated with MDDE-induced unconsciousness.

Dexmedetomidine Disrupts the Local and Global Efficiencies of Large-scale Brain Networks

“…Since sleep slow-delta (0.1 – 4 Hz) and spindle oscillations (13-16 Hz) reflect altered sensory information processing in the brainstem and thalamus, 33 it follows that dexmedetomidine-induced altered arousal which is also associated with slow-delta and spindle oscillations 34-36 should manifest with altered subcortical-cortical functional connectivity. We speculate that other anesthesia-induced slow-delta oscillations (propofol, sevoflurane, nitrous oxide), 35,37-41 theta oscillations (4-8 Hz; ketamine, sevoflurane), 37,38,42 frontal alpha oscillations (8-12 Hz; propofol, sevoflurane) 35,37-41 and gamma oscillations (< 40 Hz; ketamine) 42 may also manifest as altered subcortical-cortical and cortico-cortical fMRI bold network connectivity. A likely mechanism for this speculated finding is the disruption of “normal sensory processing” gamma oscillations (>40 Hz) that have been related to fMRI BOLD signals.…”

Using EEG markers to make inferences about anaesthetic-induced altered states of arousal

“…10,11 As a consequence, patients receiving ketamine will not form reliable alpha oscillations. Akeju and colleagues 12 demonstrated this by showing that initiation and maintenance of a ketamine infusion during sevoflurane and oxygen anaesthesia shifted alpha oscillations to beta oscillations (13e25 Hz). Mashour and Avidan 13 cite this observation in their commentary.…”

Neural oscillations demonstrate that general anesthesia and sedative states are neurophysiologically distinct from sleep

“…2A,B) [3,4,19,22**,28**-33]. Similar to sleep, a mechanism to explain these GABAergic slow-delta oscillations likely involves loss of excitatory inputs from brainstem arousal centers to the cortex [7,10**].…”

“…However, sleep spindles have a transient envelope with a refractory period of several seconds [7,25], whereas GA-induced alpha oscillations do not exhibit such a refractory period [18,21,29,30,33,39,40]. Further, GA alpha oscillations have only been found to occur with slow-delta oscillations [21,22,28-30,32,33,40], and the amplitude of GA alpha oscillations is modulated significantly by the phase of the slow-delta oscillations [33]. …”