Spatiotemporal Dynamics of Dexmedetomidine-Induced Electroencephalogram Oscillations

Abstract

An improved understanding of the neural correlates of altered arousal states is fundamental for precise brain state targeting in clinical settings. More specifically, electroencephalogram recordings are now increasingly being used to relate drug-specific oscillatory dynamics to clinically desired altered arousal states. Dexmedetomidine is an anesthetic adjunct typically administered in operating rooms and intensive care units to produce and maintain a sedative brain state. However, a high-density electroencephalogram characterization of the neural correlates of the dexmedetomidine-induced altered arousal state has not been previously accomplished. Therefore, we administered dexmedetomidine (1mcg/kg bolus over 10 minutes, followed by 0.7mcg/kg/hr over 50 minutes) and recorded high-density electroencephalogram signals in healthy volunteers, 18–36 years old (n = 8). We analyzed the data with multitaper spectral and global coherence methods. We found that dexmedetomidine was associated with increased slow-delta oscillations across the entire scalp, increased theta oscillations in occipital regions, increased spindle oscillations in frontal regions, and decreased beta oscillations across the entire scalp. The theta and spindle oscillations were globally coherent. During recovery from this state, these electroencephalogram signatures reverted towards baseline signatures. We report that dexmedetomidine-induced electroencephalogram signatures more closely approximate the human sleep onset process than previously appreciated. We suggest that these signatures may be targeted by real time visualization of the electroencephalogram or spectrogram in clinical settings. Additionally, these signatures may aid the development of control systems for principled neurophysiological based brain-state targeting.

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

“…1 However, our present results extend upon those previously reported findings by showing that functional connectivity changes between subcortical regions are not specific to any RSN. 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.…”

Electroencephalogram Similarity Analysis Using Temporal and Spectral Dynamics Analysis for Propofol and Desflurane Induced Unconsciousness

“…It is worthwhile digging into the difference and comparison to pursue some new explanation and EEG signatures related with them. In recent years, EEG related anesthetic study has focused on connectivity analysis: coherent oscillations, connectivity, and network analysis [30,36,37]. Among them, alpha band anteriorization transition process, which is associated with propofol-induced unconsciousness and surgical levels of sevoflurane anesthesia [30], is one of the most profound outcomes and perhaps is used as a marker for anesthesia depth.…”

“…This makes it hard for us to pursue detailed outcome and conclusion as well. Furthermore, multichannel analysis becomes popular more recently [26,37,38], which would enable spatial and source analysis of EEG features. For example, propofol was found with the anteriorization of alpha power [38,39].…”

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

“…Thus, the activity patterns of various arousal nuclei during dexmedetomidine-induced sedation are similar to sleep [55-60]. Therefore, with respect to amplitude and frequency characteristics, it is not surprising that dexmedetomidine slow-delta and spindle oscillations resemble N2 sleep features [29,61,62]. We note that dexmedetomidine-induced K-complexes have not been described [29,61,62].…”

“…Therefore, with respect to amplitude and frequency characteristics, it is not surprising that dexmedetomidine slow-delta and spindle oscillations resemble N2 sleep features [29,61,62]. We note that dexmedetomidine-induced K-complexes have not been described [29,61,62]. Clinically, dexmedetomidine is the only sedative agent that has been demonstrated to reduce the incidence of delirium, [63-66] an acute brain dysfunction not explained by a preexisting neurocognitive disorder.…”