Neurophysiologic Correlates of Ketamine Sedation and Anesthesia

Abstract

Background Previous studies have demonstrated inconsistent neurophysiologic effects of ketamine, although discrepant findings might relate to differences in doses studied, brain regions analyzed, coadministration of other anesthetic medications, and resolution of the electroencephalograph. The objective of this study was to characterize the dose-dependent effects of ketamine on cortical oscillations and functional connectivity. Methods Ten healthy human volunteers were recruited for study participation. The data were recorded using a 128-channel electroencephalograph during baseline consciousness, subanesthetic dosing (0.5 mg/kg over 40 min), anesthetic dosing (1.5 mg/kg bolus), and recovery. No other sedative or anesthetic medications were administered. Spectrograms, topomaps, and functional connectivity (weighted and directed phase lag index) were computed and analyzed. Results Frontal theta bandwidth power increased most dramatically during ketamine anesthesia (mean power ± SD, 4.25 ± 1.90 dB) compared to the baseline (0.64 ± 0.28 dB), subanesthetic (0.60 ± 0.30 dB), and recovery (0.68 ± 0.41 dB) states; P < 0.001. Gamma power also increased during ketamine anesthesia. Weighted phase lag index demonstrated theta phase locking within anterior regions (0.2349 ± 0.1170, P < 0.001) and between anterior and posterior regions (0.2159 ± 0.1538, P < 0.01) during ketamine anesthesia. Alpha power gradually decreased with subanesthetic ketamine, and anterior-to-posterior directed connectivity was maximally reduced (0.0282 ± 0.0772) during ketamine anesthesia compared to all other states (P < 0.05). Conclusions Ketamine anesthesia correlates most clearly with distinct changes in the theta bandwidth, including increased power and functional connectivity. Anterior-to-posterior connectivity in the alpha bandwidth becomes maximally depressed with anesthetic ketamine administration, suggesting a dose-dependent effect.

Measuring depth of anaesthesia using changes in directional connectivity: a comparison with auditory middle latency response and estimated bispectral index during propofol anaesthesia

“…The observed switch in the direction of connectivity from wakefulness to anaesthesia is consistent with other studies investigating EEG directional connectivity during anaesthesia . In contrast with our results, some studies have reported an impairment of fronto‐posterior connectivity when consciousness is lost . These conflicting findings are likely to result from the use of different estimators of connectivity that may quantify diverse effects.…”

“…A small number of recent studies have investigated EEG connectivity during anaesthesia, with promising results. These studies are characterised by a variety of experimental protocols and connectivity estimators, either linear Granger causality estimators or non‐linear approaches based on information theory or phase dynamics . However, it is not clear how directional connectivity measures correlate with established depth of anaesthesia indices because, to our knowledge, a comparison of connectivity changes during anaesthesia with other indices has not been performed.…”

In search of Universal Cortical Power Changes Linked to NMDA-Antagonist based Anesthetic Induced Reductions in Consciousness

“…The absence of N 2 O-induced theta band changes has been previously reporded 54 , however remains unlike most reports pointing to theta power increases under N 2 O 15,16 and ketamine 12,32,55,56 . The significant reduction in electroencephalographic alpha power upon subanesthetic N 2 O administration has been observed 13,54 and replicated using ketamine anesthetic dosage 56 . Importantly, due to the close resemblance to our paradigm, a theta rise was replicated using magnetoencephalography and subanesthetic ketamine doses 32 .…”

“…Xe did not significantly alter alpha power, as has been formerly presented 17 . A general point to be made here is that observed power changes, can be complemented by functional connectivity measures which may yield more powerful functional specificity 56 (such investigations will be the subject of future work). The distinctive effects of the two agents on the theta and alpha band we outlined by contrasting their anesthetic action on each individual, may ultimately relate to large-scale (low frequency dependent) network alterations along the anterior to posterior axis, but further investigations are required to consider this postulation.…”

Mechanisms of hysteresis in human brain networks during transitions of consciousness and unconsciousness: Theoretical principles and empirical evidence

“…We used high-density EEG data from two independent studies using ketamine and sevoflurane; detailed methodology can be found in the S1 Text and the previous studies by Vlisides et al[ 23 ] (ketamine) and Blain-Moraes et al[ 24 ] (sevoflurane). For this study, we selected four states (baseline, induction, unconscious, and emergence) from the state transitions of each data set.…”