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Method Article

Recording Brain Electromagnetic Activity During the Administration of the Gaseous Anesthetic Agents Xenon and Nitrous Oxide in Healthy Volunteers

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DOI:

10.3791/56881

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January 13th, 2018

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In This Article

Summary

Simultaneous magnetoencephalography and electroencephalography provides a useful tool to search for common and distinct macro-scale mechanisms of reductions in consciousness induced by different anesthetics. This paper illustrates the empirical methods underlying the recording of such data from healthy humans during N-Methyl-D-Aspartate-(NMDA)-receptor-antagonist-based anesthesia during inhalation of nitrous oxide and xenon.

Abstract

Anesthesia arguably provides one of the only systematic ways to study the neural correlates of global consciousness/unconsciousness. However to date most neuroimaging or neurophysiological investigations in humans have been confined to the study of γ-Amino-Butyric-Acid-(GABA)-receptor-agonist-based anesthetics, while the effects of dissociative N-Methyl-D-Aspartate-(NMDA)-receptor-antagonist-based anesthetics ketamine, nitrous oxide (N2O) and xenon (Xe) are largely unknown. This paper describes the methods underlying the simultaneous recording of magnetoencephalography (MEG) and electroencephalography (EEG) from healthy males during inhalation of the gaseous anesthetic agents N2O and Xe. Combining MEG and EEG data enables the assessment of electromagnetic brain activity during anesthesia at high temporal, and moderate spatial, resolution. Here we describe a detailed protocol, refined over multiple recording sessions, that includes subject recruitment, anesthesia equipment setup in the MEG scanner room, data collection and basic data analysis. In this protocol each participant is exposed to varying levels of Xe and N2O in a repeated measures cross-over design. Following relevant baseline recordings participants are exposed to step-wise increasing inspired concentrations of Xe and N2O of 8, 16, 24 and 42%, and 16, 32 and 47% respectively, during which their level of responsiveness is tracked with an auditory continuous performance task (aCPT). Results are presented for a number of recordings to highlight the sensor-level properties of the raw data, the spectral topography, the minimization of head movements, and the unequivocal level dependent effects on the auditory evoked responses. This paradigm describes a general approach to the recording of electromagnetic signals associated with the action of different kinds of gaseous anesthetics, which can be readily adapted to be used with volatile and intravenous anesthetic agents. It is expected that the method outlined can contribute to the understanding of the macro-scale mechanisms of anesthesia by enabling methodological extensions involving source space imaging and functional network analysis.

Introduction

There is good consensus between pre-clinical and clinical neuroscientific evidence suggesting that the phenomenon of human consciousness depends on the integrity of explicit neural circuits. The observation that such circuits are systematically influenced by the descent into unconsciousness has substantiated the need for neuroimaging techniques to be utilized during anesthesia and enable 'navigating' the search for the neural correlates of consciousness. With the possible exception of sleep, anesthesia represents the only method by which one can, in a controlled, reversible and reproducible fashion, perturb, and thus dissect, the mechanisms that sub-serve cons....

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Protocol

The study entitled "Effects of inhaled Xe and N2O on brain activity recorded using EEG and MEG" was approved (approval number: 260/12) by the Alfred Hospital and Swinburne University of Technology Ethics Committee and met the requirements of the National Statement on Ethical Conduct in Human Research (2007).

1. Participant Selection and Pre-Study Requirements

  1. Conduct an interview to select healthy, right handed, adult males between the ages of 20 and 40 years old.
    1. Confirm a good general health status by obtaining the participant's Body Mass Index (BMI) and the lack of contraindications to MRI or MEG (such ....

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Results

This section utilizes data obtained from one subject in order to demonstrate the typical features of the simultaneous recordings and the potential of such information to contribute a better understanding of anesthetic induced altered states of consciousness. To simplify the exposition, results are shown for i) recordings of the post-anti-emetic administration baseline (baseline 3), ii) 0.75 equi-MAC-awake peak gas concentrations (level 3) of N2O (47%) and Xe (24%), and iii) Xe .......

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Discussion

This paper has outlined a comprehensive protocol for the simultaneous recording of MEG and EEG during anesthetic gas delivery with N2O and Xe. Such a protocol will be valuable for studying the electromagnetic neural correlates of anesthetic-induced reductions in consciousness. The protocol is also expected to generalize to the delivery of other anesthetic gases such as sevoflurane or isoflurane. This will facilitate a greater understanding of the common, specific and distinct macroscopic mechanisms that underl.......

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Disclosures

The authors have nothing to disclose.

Acknowledgements

The authors would like to thank Mahla Cameron Bradley, Rachel Anne Batty and Johanna Stephens for valuable technical assistance with MEG data collection. Thanks are additionally extended to Dr. Steven Mcguigan for support as a second anesthesiologist. Paige Pappas provided invaluable anesthetic nurse oversight. Markus Stone graciously proffered his time and expertise in editing and filming the protocol. Dr. Suresh Muthukumaraswamy gave specific advice regarding data analysis and the interpretation of results. Finally, Jarrod Gott contributed many a stimulating discussion, helped in the execution of a number of pilot experiments and was central in the design of the foa....

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Materials

List of materials used in this article
NameCompanyCatalog NumberComments
Neuromag TRIUX 306-channel MEG systemElekta Oy, Stockholm, SWEDENN/A
Polhemus Fastrak 3D systemPolhemus, VT, USAN/A
MEG compatible ER-1 insert headphonesEtymotic Research Inc., IL, USAN/A
Low Density foam head cap, MEG compatibleN/AN/ACustom made by research team
Harness, MEG compatibleN/A~3 m long, ~ 5 cm wide, cloth/jute strip to secure participant position on MEG chair
Ambu Neuroline 720 Single Patient Surface ElectrodesAmbu, Copenhagen, Denmark72015-K10
3.0T TIM Trio MRI systemSiemens AB, Erlangen, GERMANYN/A
Asalab amplifier systemANT Neuro, Enschede, NETHERLANDSN/Athis system is no longer manufactured and has been deprecated to 64 channel eego EEG amplifier
64-channel Waveguard EEG cap, MEG compatibleANT Neuro, Enschede, NETHERLANDSCA-138size Medium
Magnetically shielded cordless battery boxANT Neuro, Enschede, NETHERLANDSN/AMagnetic shielding not provided by manufacturer – Modified by research team
OneStep ClearGel Electrode gelH+H Medizinprodukte GbR, Munster, GERMANY154547
Akzent Xe Color Anesthesia MachineStephan GmbH, Gackenbach, GERMANYN/A
Omron M6-Comfort Blood Pressure MonitorOmron Healthcare, Kyoto, JAPANN/A
Xenon gas (99.999% purity)Coregas, Thomastown, VIC, AUSTRALIAN/Awe estimate that we use approx 40 L (SATP) per participant
Medical Nitrous OxideCoregas, Thomastown, VIC, AUSTRALIAN/Ax2 G size cylinders
Medical OxygenCoregas, Thomastown, VIC, AUSTRALIAN/Ax2 G size cylinders
Medical AirCoregas, Thomastown, VIC, AUSTRALIAN/Ax2 G size cylinders
Filter Respiratory & HMES with Capno Port HypnobagMedtronic, MN, USA352/5805
Yankauer High AdultMedtronic, MN, USA8888-502005
Quadralite EcoMask anaesthetic masksIntersurgical Australia Pty Ltd7093000/7094000size 3 and size 4
Suction Canister Disp 1200 mL Medival GuardianCardinal Health, OH, USA65651-212
Catheter Mount Ext 4-13 cm with  90A elbowMedtronic, MN, USA330/5667
Catheter IV Optiva 24g x 19 mm Yellow St SuSmiths Medical, MN, USA5063-INT
Dexamethasone Mylan Injection Vials (4 mg/1 mL)Alphapharm Pty Ltd, Sydney, AUSTRALIA400528517
Ondasetron (4 mg/2 mL)Alphapharm Pty Ltd, Sydney, AUSTRALIA400008857
Medical resuscitation cartThe medical resuscitation cart is configured according to the suggested minimal requirements for Adult resuscitation recommended in the document "Standards for Resuscitation: Clinical Practice and Education; June 2014) by the Australian and New Zealand Resuscitation councils and specifically endorsed by multiple professional health care organizations including the Australian and New Zealand College of Anaesthetists.  It includes all the necessary airway and circulatory equipment, as well as the associated pharmacuetical agents to enable full cardio-respiratory resuscitation and support in a non-clinical environment.  Full details can be found at https://resus.org.au/standards-for-resuscitation-clinical-practice-and-education/
Maxfilter Version 2.2Elekta Oy, Stockholm, SWEDENN/AData analysis software provided with Elekta's Neuromag TRIUX MEG system

References

  1. Hudetz, A. Suppressing the Mind. Hudetz, A., Pearce, R. , 178-189 (2010).
  2. Franks, N. P., Dickinson, R., de Sousa, S. L., Hall, A. C., Lieb, W. R. How does xenon produce anaesthesia? Nature. 396 (6709), 324(1998).
  3. Jevtović-Todorović, V., Todorović, S. M., Mennerick, S., Powell, S., Dikranian, K., Benshoff, N., Zorumski, C. F., Olney, J. W.

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