Anesthetic action on the transmission delay between cortex and thalamus explains the beta-buzz observed under propofol anesthesia

Hashemi, Meysam; Hutt, Axel; Hight, Darren; Sleigh, Jamie

doi:10.1371/journal.pone.0179286

Cited by 17 publications

(15 citation statements)

References 95 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Input was a constant direct-current to thalamic relay cells. The cortex-thalamus-cortex loop took 80 ms, made up of 60 ms cortex to thalamus and 20 ms thalamus to cortex, in accordance with previous models 51,52 . The spectral response was calculated by…”

Section: Modelling Analysissupporting

confidence: 87%

Generative modelling of the thalamo-cortical circuit mechanisms underlying the neurophysiological effects of ketamine

Shaw

Muthukumaraswamy

Saxena

et al. 2019

Preprint

View full text Add to dashboard Cite

Abbreviations: N-methyl-D-aspartate (NMDA), gamma-aminobuyric acid (GABA), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA). Model population abbreviations: Population nameAbbrv. Superficial layer pyramidal (L2/3) SP Superficial layer interneuron (L2/3) SI Spiny Stellate (Layer 4) SS Deep layer pyramidal (Layer 5) DP Deep layer interneuron (Layer 5) DI Thalamic projection pyramidal (Layer 6) TP Thalamic Reticular RT Thalamic Relay RL Abstract Cortical recordings of task-induced oscillations following subanaesthetic ketamine administration demonstrate alterations in amplitude, including increases at high-frequencies (gamma) and reductions at low frequencies (theta, alpha). To investigate the population-level interactions underlying these changes, we implemented a thalamo-cortical model capable of recapitulating broadband spectralresponses. Compared with placebo, ketamine was found to increase the decay rate of NMDA receptor currents, decrease the decay rate of GABA-B receptor currents, but had no effect on AMPA or GABA-A currents. Furthermore, ketamine decreased the inhibitory self-modulation of superficial pyramidal populations, increased the inhibitory self-modulation of inhibitory interneurons and increased the strength of the cortico-thalamic projection from layer 6 into thalamus. In-silico rectification of each of these parameters to their placebo state revealed the accompanying spectral changes. Similar broadband effects were demonstrated for the NMDA constant and intrinsic connectivity changes, whereby rectification resulted in normalising the amplitude of alpha (increased) and gamma (decreased). While supporting theories of superficial pyramidal disinhibition following ketamine administration, our results suggest a role for altered cortico-thalamic connectivity relevant to understanding ketamine induced cortical responses and potentially identifies a system-level mechanism contributing to its antidepressant effects. Sample characteristicsDetails of the sample and procedures of this study have been reported previously, see Shaw et al 2015 11 . Twenty healthy (American Society of Anaesthesiologists, physical status Class 1), nonsmoking, male volunteers with a BMI of 18-30 kg/m 2 and aged between 18 -45 took part in the study.All subjects gave informed consent, with experimental procedures approved by the UK National Research Ethics Service in South East Wales. Subjects were screened for personal history of neurological or psychiatric disease by the Mini International Neuropsychiatric Interview 34 . Exclusion criteria further included contraindications to MEG or magnetic resonance imaging (MRI), and selfreported needle phobia. Visual paradigm Subjects were presented with an annular, stationary, square-wave visual grating of spatial frequency 3 cycles per degree on a mean luminance background. Gratings were displayed 150 times, with 75 at 100% contrast and 75 at 75% contrast 35 . Grating visual angle was 8º. Subjects were instructed to focus on a small, red, continually displayed dot at the centre o...

show abstract

Section: Modelling Analysissupporting

confidence: 87%

Generative modelling of the thalamo-cortical circuit mechanisms underlying the neurophysiological effects of ketamine

Shaw

Muthukumaraswamy

Saxena

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…When inducing a patient with propofol, the EEG changes to faster oscillatory rhythm which causes a transient increase in the beta band power 17 , 48 . This episode is called paradoxical excitation 16 or beta-buzz 49 . Modelling work on the mechanisms of the paradoxical excitation describe that this phenomenon may be caused by interneuron antisynchrony 50 and/or by propofol causing a delay in transmission between cortical and thalamic structures 49 .…”

Section: Discussionmentioning

confidence: 99%

“…This episode is called paradoxical excitation 16 or beta-buzz 49 . Modelling work on the mechanisms of the paradoxical excitation describe that this phenomenon may be caused by interneuron antisynchrony 50 and/or by propofol causing a delay in transmission between cortical and thalamic structures 49 . In humans, findings also show that the effect on brain metabolism is similar in the thalamus and the cortex 51 .…”

Section: Discussionmentioning

confidence: 99%

The influence of induction speed on the frontal (processed) EEG

Obert

Sepúlveda

Kratzer

et al. 2020

Sci Rep

View full text Add to dashboard Cite

The intravenous injection of the anaesthetic propofol is clinical routine to induce loss of responsiveness (LOR). However, there are only a few studies investigating the influence of the injection rate on the frontal electroencephalogram (EEG) during LOR. Therefore, we focused on changes of the frontal EEG especially during this period. We included 18 patients which were randomly assigned to a slow or fast induction group and recorded the frontal EEG. Based on this data, we calculated the power spectral density, the band powers and band ratios. To analyse the behaviour of processed EEG parameters we calculated the beta ratio, the spectral entropy, and the spectral edge frequency. Due to the prolonged induction period in the slow injection group we were able to distinguish loss of responsiveness to verbal command (LOvR) from loss of responsiveness to painful stimulus (LOpR) whereas in the fast induction group we could not. At LOpR, we observed a higher relative alpha and beta power in the slow induction group while the relative power in the delta range was lower than in the fast induction group. When concentrating on the slow induction group the increase in relative alpha power pre-LOpR and even before LOvR indicated that frontal EEG patterns, which have been suggested as an indicator of unconsciousness, can develop before LOR. Further, LOvR was best reflected by an increase of the alpha to delta ratio, and LOpR was indicated by a decrease of the beta to alpha ratio. These findings highlight the different spectral properties of the EEG at various levels of responsiveness and underline the influence of the propofol injection rate on the frontal EEG during induction of general anesthesia.

show abstract

“…PY and TC cells propagated with AMPA receptors, while IN cells and RE cells with GABAa receptors. As the delay between cortex and thalamus is described in biological observation (Hashemi et al, 2017), the delay from thalamus to cortex was set as 20 ms, while from cortex to thalamus was set as 60 ms. Synaptic connection between each cells were modified according to the results of previous studies (Figure 1 and Table 2) (Destexhe et al, 1998;Ching et al, 2010;Hayut et al, 2011;Fogerson and Huguenard, 2016;Krishnan et al, 2016).…”

Section: Modelmentioning

confidence: 99%

A Potential Mechanism of Sodium Channel Mediating the General Anesthesia Induced by Propofol

Xiao

Chen

2020

Front. Cell. Neurosci.

View full text Add to dashboard Cite

General anesthesia has revolutionized healthcare over the past 200 years and continues to show advancements. However, many phenomena induced by general anesthetics including paradoxical excitation are still poorly understood. Voltage-gated sodium channels (NaV) were believed to be one of the proteins targeted during general anesthesia. Based on electrophysiological measurements before and after propofol treatments of different concentrations, we mathematically modified the Hodgkin–Huxley sodium channel formulations and constructed a thalamocortical model to investigate the potential roles of NaV. The ion channels of individual neurons were modeled using the Hodgkin–Huxley type equations. The enhancement of propofol-induced GABAa current was simulated by increasing the maximal conductance and the time-constant of decay. Electroencephalogram (EEG) was evaluated as the post-synaptic potential from pyramidal (PY) cells. We found that a left shift in activation of NaV was induced primarily by a low concentration of propofol (0.3–10 μM), while a left shift in inactivation of NaV was induced by an increasing concentration (0.3–30 μM). Mathematical simulation indicated that a left shift of NaV activation produced a Hopf bifurcation, leading to cell oscillations. Left shift of NaV activation around a value of 5.5 mV in the thalamocortical models suppressed normal bursting of thalamocortical (TC) cells by triggering its chaotic oscillations. This led to irregular spiking of PY cells and an increased frequency in EEG readings. This observation suggests a mechanism leading to paradoxical excitation during general anesthesia. While a left shift in inactivation led to light hyperpolarization in individual cells, it inhibited the activity of the thalamocortical model after a certain depth of anesthesia. This finding implies that high doses of propofol inhibit the network partly by accelerating NaV toward inactivation. Additionally, this result explains why the application of sodium channel blockers decreases the requirement for general anesthetics. Our study provides an insight into the roles that NaV plays in the mechanism of general anesthesia. Since the activation and inactivation of NaV are structurally independent, it should be possible to avoid side effects by state-dependent binding to the NaV to achieve precision medicine in the future.

show abstract

Anesthetic action on the transmission delay between cortex and thalamus explains the beta-buzz observed under propofol anesthesia

Cited by 17 publications

References 95 publications

Generative modelling of the thalamo-cortical circuit mechanisms underlying the neurophysiological effects of ketamine

Generative modelling of the thalamo-cortical circuit mechanisms underlying the neurophysiological effects of ketamine

The influence of induction speed on the frontal (processed) EEG

A Potential Mechanism of Sodium Channel Mediating the General Anesthesia Induced by Propofol

Contact Info

Product

Resources

About