State-Dependent and Bandwidth-Specific Effects of Ketamine and Propofol on Electroencephalographic Complexity in Rats.

Michael A Brito,Dinesh Pal,Duan Li,George A Mashour

doi:10.3389/fnsys.2020.00050

Michael A Brito, Dinesh Pal + Show 2 more

Open Access

https://doi.org/10.3389/fnsys.2020.00050

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Abstract

There is an ongoing debate as to whether ketamine anesthesia suppresses neurophysiologic complexity at doses sufficient for surgical anesthesia, with previous human studies reporting surrogates of both suppressed and preserved levels of cortical complexity. However, these studies have not assessed cortical dynamics in higher gamma frequencies, which have previously been demonstrated to correlate with the level of consciousness during anesthesia. In this study, we used Lempel-Ziv complexity (LZc) to characterize frontal and parietal electroencephalographic complexity (0.5–175 Hz, 0.5–55 Hz, 65–175 Hz) before, during, and after ketamine or propofol anesthesia in the rat. To control for the potential influence of spectral changes in complexity estimation, LZc was normalized with phase-shuffled surrogate data. We demonstrate that ketamine and propofol anesthesia were characterized by a significant reduction in broadband (0.5–175 Hz) LZc. Further analysis showed that while the reduction of LZc during ketamine anesthesia was significant in 65–175 Hz range, during propofol anesthesia, a significant decrease was observed in 0.5–55 Hz bandwidth. LZc in broadband and 0.5–55 Hz range showed a significant increase during emergence from ketamine anesthesia. Phase-shuffled normalized LZc revealed that (1) decrease in complexity during ketamine and propofol anesthesia—not increase in complexity during emergence—were dissociable from the influence of spectral changes, and (2) reduced LZc during ketamine anesthesia was present across all three bandwidths. Ketamine anesthesia was characterized by reduced complexity in high gamma bandwidth, as reflected in both raw and phase-shuffled normalized LZc, which suggests that reduced high gamma complexity is a neurophysiological feature of ketamine anesthesia.

Highlights

There is still a debate as to the precise neural correlates of consciousness (Boly et al, 2017; Odegaard et al, 2017; Mashour, 2018), several theories are converging upon the idea that the capacity for conscious experience relates to the diversity of states that the brain can generate (Seth et al, 2006; Baars et al, 2013; Tononi et al, 2016; Carhart-Harris, 2018)
We found the Lempel-Ziv complexity (LZc) values to be highest during this phase as compared to wake state (frontal: t(7) = 14.097, p < 0.001; parietal: t(7) = 18.626, p < 0.00), and ketamine anesthesia (frontal: t(7) = 19.439, p < 0.001; parietal: t(7) = 18.628, p < 0.001; FIGURE 1 | Schematic illustrating the experimental design for electroencephalographic recordings before, during, and after ketamine (A) and propofol (B) anesthesia. i.p., intraperitoneal; i.v., intravenous
Using intracranial EEG data from frontal and parietal cortices of rats receiving ketamine or propofol anesthesia, we demonstrate a reduction in broadband (0.5–175 Hz) EEG complexity during ketamine anesthesia that is comparable to that induced by GABAergic anesthetic propofol

Summary

Introduction

There is still a debate as to the precise neural correlates of consciousness (Boly et al, 2017; Odegaard et al, 2017; Mashour, 2018), several theories are converging upon the idea that the capacity for conscious experience relates to the diversity of states that the brain can generate (Seth et al, 2006; Baars et al, 2013; Tononi et al, 2016; Carhart-Harris, 2018). From the perspective of its effects on EEG signal diversity, ketamine diverges from traditional anesthetics at subanesthetic concentrations, as it induces dissociative psychedelic states characterized by a maintained or enhanced repertoire of brain states (Schartner et al, 2017a; Li and Mashour, 2019). This is in contrast to GABAergic anesthetics such as propofol, which have been shown to degrade sensory integration and attenuate neural signal diversity in a dose-dependent manner (Ferenets et al, 2006, 2007; Ishizawa et al, 2016). Dreaming has been reported in patients receiving GABAergic anesthetic agents such as propofol, the occurrence is reported to be much less common and is often associated with simple phenomenological content more typical of slow-wave sleep (Leslie et al, 2007; Leslie, 2010)

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