Name: recording brain electromagnetic activity during the administration of the gaseous anesthetic agents xenon and nitrous oxide in healthy volunteers
Uploaded: 2018-01-13T14:00:00
Description: Watch this Scientific Journal Video about Recording Brain Electromagnetic Activity During the Administration of the Gaseous Anesthetic Agents Xenon and Nitrous Oxide in Healthy Volunteers at JoVE.com

Forfatterne vil gerne takke Mahla Cameron Bradley, Rachel Anne Batty og Johanna Stephens for værdifulde tekniske bistand med MEG dataindsamling. Tak er desuden udvidet til Dr. Steven Mcguigan for støtte som en anden anæstesilæge. Paige Pappas givet uvurderlig bedøvelsesmiddel sygeplejerske tilsyn. Markus Stone tilbudt allernådigst sin tid og ekspertise i redigering og filme i protokollen. Dr. Suresh Muthukumaraswamy gav specifikke råd med hensyn til dataanalyse og fortolkning af resultaterne. Endelig Jarrod Gott bidrog mange en stimulerende debat, hjalp i udførelsen af en række pilotforsøg og var et centralt i design af skum hoved skinnen.
Denne forskning blev støttet af en James S. McDonnell collaborative grant #220020419 "Rekonstruere bevidsthed" tildelt til George Mashour, Michael Avidan, Max Kelz og David Liley.

Undersøgelsen med titlen "Virkning af inhalerede Xe og N2O på hjerneaktivitet registreres ved hjælp af EEG og MEG" blev godkendt (godkendelsesnummer: 260/12) af Alfred Hospital og Swinburne University of Technology etiske komité og opfyldt kravene i nationale Redegørelse om etisk adfærd i Human forskning (2007).
1. deltager udvælgelse og forundersøgelse krav
<ol><li>Gennemføre et interview for at vælge sundt, højrehåndet, voksne mænd i alderen mellem 20 og 40 år gaml...

Dette papir har skitseret en omfattende protokol for den samtidige optagelse af MEG og EEG under narkose gas levering med N2O og Xe. Sådan en protokol vil være værdifuld for at studere de elektromagnetiske neurale korrelerer med narkose-induceret reduktioner i bevidsthed. Protokollen forventes også at generalisere til levering af andre bedøvende gasser som Sevofluran eller isofluran. Dette vil lette en større forståelse for de fælles, specifikke og særskilte makroskopisk mekanismer, der ligger bag an?...

Der er god enighed mellem prækliniske og kliniske neurovidenskabelige beviser tyder på, at fænomenet med menneskets bevidsthed afhænger af integriteten af eksplicitte neurale kredsløb. Den iagttagelse, at sådanne kredsløb systematisk er påvirket af nedstigningen til bevidstløshed har dokumenteret behovet for neuroimaging teknikker til at blive udnyttet under anæstesi og aktiverer 'navigation' søgning efter de neurale korrelerer af bevidsthed. Med undtagelse af søvn, anæstesi repræsenterer den eneste metode, hvormed man kan, i en kontrolleret, reversible og reproducerbare mode, forurolige og dermed dissekere de mekanismer, som sub tjene bevidsthed, især på makroskopisk skala af Global hjerne dynamics. Klinisk, generel anæstesi kan defineres som en tilstand af hypnose/bevidstløshed, immobilitet og analgesi og fortsat er en af mest talrigt anvendte og sikreste medicinsk indgreb. Trods den klarhed og effektivitet i det endelige resultat, er der stadig stor usikkerhed om virkningsmekanisme af de forskellige typer af agenter giver anledning til bedøvelsesmiddel induceret bevidstløshed1.
Narkose kan opdeles i intravenøs agenter navnlig propofol og barbiturater eller de flygtige/gasformige stoffer såsom Sevofluran, isofluran, lattergas (N2O) og xenon (Xe). Farmakologi af anæstesi har været veletableret med flere cellulære mål identificeret som forbundet med bedøvende handling. De fleste agenter studerede til dato act hovedsagelig via agonisme γ-Amino-Butyric-Acid-(GABA) receptor medieret aktivitet. I kontrast, dissociative agenter ketamin, menes Xe og N2O at udøve deres virkninger af primært rettet mod N-Methyl-D-Aspartate-(NMDA) glutamatergic receptorer2,3. Andre vigtige farmakologiske mål omfatter kalium kanaler, acetylcholin receptorer og rest glutamat receptorer, AMPA og kainate, men omfanget af deres bidrag til bedøvende handling er stadig undvigende (for en omfattende gennemgang Se 4).
Omfanget af variation i virkningsmekanismen og de observerede fysiologiske og neurale virkninger af de forskellige typer af agenter gengiver afledning af generelle konklusioner om deres indflydelse på bevidst forarbejdning vanskeligt. Tab af bevidsthed (LOC) induceret af GABAergic agenter er typisk karakteriseret ved en global ændring i hjerneaktivitet. Dette er tydeligt i fremkomsten af høj-amplitude, lavfrekvente delta (δ, 0,5-4 Hz) bølger og reduktion i høj frekvens, gamma (γ, 35-45Hz) aktivitet i elektroencefalografi (EEG), svarende til langsom bølge sove5,6 samt de udbredte reduktioner i cerebral blood flow og glukose metabolismen5,6,7,8,9,10,,11,12 . Boveroux mfl. 13 tilføjet til sådanne bemærkninger ved at demonstrere en betydelig nedgang i hvilende tilstand funktionelle forbindelse under propofol anæstesi ved hjælp af funktionel magnetisk resonans imaging (fMRI). Derimod dissociative anæstetika give en mindre klar profil af effekter på hjerneaktivitet. I nogle tilfælde er de forbundet med stigninger i cerebral blood flow og glukose metabolismen14,15,16,17,18,19, 20,21 mens undersøgelser af Rex og kolleger22 og Laitio og kolleger23,24 ser på virkningerne af Xe leveres beviser for både større og mindre hjerne aktivitet. En lignende uregelmæssighed kan ses i virkningerne på EEG-signaler25,26,27,28. Johnson mfl. 29 viste en stigning i total magt af lavfrekvent bands delta og theta såvel som i den højere frekvens band gamma i en høj densitet EEG undersøgelse af Xe anæstesi mens modstridende observationer blev gjort for N2O i delta, theta og Alpha frekvens båndene30,31 og for Xe i de højere frekvenser32. Sådanne variabilitet i virkningerne af Xe på elektriske hovedbunden aktivitet kan observeres i alfa og beta frekvensområder også med både øger33 og reduktioner34 rapporteres.
Trods de forskelle, der er nævnt ovenfor, begynder billedet at blive mere konsekvent på tværs af agenter, når man forsøger at se på ændringer i funktionelle forbindelse mellem områder i hjernen. Sådanne foranstaltninger har dog været overvejende begrænset til modaliteter, der nødvendigvis gøre indrømmelser for enten rumlige eller tidsmæssige opløsning. Mens undersøgelser ved hjælp af EEG synes at afsløre klare, og til dels konsekvent, ændringer i den topologisk struktur af funktionelle netværk under anæstesi/sedation med propofol35, Sevofluran36 og N2O37, den bredt fordelte sensor niveau EEG data har utilstrækkelig rumlige opløsning meningsfuldt definere og afgrænse vertices i de tilsvarende funktionelle netværk. Omvendt finde undersøgelser udnytte de overlegne rumlige opløsning af fMRI og positron emission tomografi (PET), lignende topologiske forandringer i stor skala funktionelle tilslutningsmuligheder som EEG13,38,39 ,40,41, men besidder utilstrækkelig tidsmæssige opløsning til at karakterisere fase-amplitude kobling i alpha (8-13 Hz) EEG bandet og andre dynamiske fænomener, der er ved at opstå som vigtige underskrifter af bedøvende handling12,42. Desuden, disse foranstaltninger ikke direkte vurdere elektromagnetiske neurale aktivitet43.
Derfor, for at meningsfuldt fremme forståelsen af de makroskopiske processer forbundet med handlingen af anæstetika, begrænsninger af de tidligere nævnte undersøgelser skal løses; begrænset dækning af bedøvelsesmiddel agenter og den utilstrækkelige spatio-temporal opløsning af ikke-invasive målinger. På dette grundlag, forfatterne skitsere en metode til samtidig registrere magnetoencephalogram (MEG) og EEG aktivitet i raske frivillige, der er blevet udviklet for administrationen af de gasformige dissociative bedøvelsesmiddel agenter, Xe og N2O.
MEG udnyttes som det er den kun non-invasiv neurofysiologiske teknik end EEG, der har en tidsmæssig opløsning i rækken millisekund. EEG har problemet med sløring af elektriske felter af kraniet, der fungerer som et low-pass filter på cortically genereret aktivitet, mens MEG er langt mindre følsomme over for dette problem og spørgsmålet om volumen overledning44. Det kan hævdes, at MEG har højere rumlige og kilde lokalisering nøjagtighed end EEG 45,46. EEG tillader ikke sandt reference-gratis optagelse37,47, men MEG gør. MEG systemer optage også typisk kortikale aktivitet i en meget større frekvensområde end EEG, herunder høj gamma48(typisk 70-90 Hz), som er blevet foreslået for at være involveret i de hypnotiske virkningerne af bedøvelsesmiddel agenter herunder Xe29 og N 2 O28. MEG tilbyder neurofysiologiske aktivitet, der komplimenterer der formidles af EEG, som EEG aktivitet vedrører ekstracellulære elektriske strømme, hvorimod MEG afspejler hovedsagelig de magnetiske felter genereret af intracellulære strømninger46, 49. Desuden MEG er særligt følsomme over for elektrofysiologiske aktivitet tangerer cortex, mens EEG det meste optegnelser ekstracellulære aktivitet radial-cortex49. Dermed kombinere MEG og EEG data har super-additiv fordele50.
Den gasformige dissociative agenter Xe og N2O er blevet valgt af følgende princip grunde: de er lugtfri (Xe) eller hovedsagelig lugtfri (N2O) og dermed nemt kan udnyttes i overværelse af kontrol betingelser når ansat på subklinisk koncentrationer. Derudover er de velegnede til fjernadministration og overvågning i et laboratoriemiøj på grund af deres svage hjerte-respiratorisk hæmmende effekter61. Xenon og til en mindre grad N2O, bevarer en forholdsvis lav minimum-alveolære - koncentration-(MAC)-vågen på hvor 50% af patienterne blive unresponsive på en verbal kommando med værdier af 32,6 ± 6,1%51 og 63,3 + - 7,1%52 henholdsvis. Trods Xe og N2O både at være NMDA-antagonister, de modulere EEG forskelligt - Xe vises opfører sig mere som en typisk GABAergic agent når overvåges ved hjælp af Bispectral indeks33,53,54 (en af flere metoder, der anvendes til electroencephalographically overvåge dybde af anæstesi). Derimod producerer N2O en langt mindre tilsyneladende electroencephalographic effekt i, at det er dårligt, hvis overhovedet, overvåges ved hjælp af Bispectral indeks26. Fordi Xe har forskellige rapporterede electroencephalographic egenskaber til de andre dissociative agenter, men har lignende egenskaber til de mere almindeligt studerede GABAergic agenter, har dets elektrofysiologiske undersøgelse potentiale til at afsløre vigtige funktioner vedrørende de neurale korrelerer bevidsthed og de tilsvarende netværksændringer af funktionelle. Agenter, der handler på NMDA-receptor er tilbøjelige til at afsløre mere om hjernens netværk, at subserve normale og ændret bevidsthed, givet den kritiske rolle, som NMDA-receptor medieret aktivitet spiller i indlæring og hukommelse og dets implicerede rolle i en række psykiatriske lidelser, der omfatter skizofreni og depression80.
Dette papir fokuserer primært på den krævende og komplekse dataindsamlingsprocedure forbundet med levering af gasformige bedøvelsesmiddel agenter i en ikke-hospitalsmiljø mens samtidig optagelse MEG og EEG. Grundlæggende dataanalyse på sensoren niveau er skitseret og eksempeldata leveres illustrerer, at high-fidelity optagelser kan opnås med minimal hoved bevægelse. De mange potentielle metoder til efterfølgende kilde billedbehandling og/eller funktionelle connectivity analyse, der typisk ville udføres ved hjælp af denne slags data er ikke beskrevet, som disse metoder er godt beskrevet i litteraturen og vise forskellige muligheder for analyse55,56.

<table border="0" cellpadding="0" cellspacing="0" width="681">
	<tbody>
		<tr height="63">
			<td height="63" style="height:63px;width:216px;">Neuromag TRIUX 306-channel MEG system</td>
			<td style="width:115px;">Elekta Oy, Stockholm, SWEDEN</td>
			<td style="width:119px;">N/A</td>
			<td style="width:231px;"></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">Polhemus Fastrak 3D system</td>
			<td style="width:115px;">Polhemus, VT, USA</td>
			<td style="width:119px;">N/A</td>
			<td style="width:231px;"></td>
		</tr>
		<tr height="63">
			<td height="63" style="height:63px;width:216px;">MEG compatible ER-1 insert headphones</td>
			<td style="width:115px;">Etymotic Research Inc., IL, USA</td>
			<td style="width:119px;">N/A</td>
			<td style="width:231px;"></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">Low Density foam head cap, MEG compatible</td>
			<td style="width:115px;">N/A</td>
			<td style="width:119px;">N/A</td>
			<td style="width:231px;">Custom made by research team</td>
		</tr>
		<tr height="63">
			<td height="63" style="height:63px;width:216px;">Harness, MEG compatible</td>
			<td style="width:115px;">N/A</td>
			<td style="width:119px;"></td>
			<td style="width:231px;">~3 m long, ~ 5 cm wide, cloth/jute strip to secure participant position on MEG chair</td>
		</tr>
		<tr height="63">
			<td height="63" style="height:63px;width:216px;">Ambu Neuroline 720 Single Patient Surface Electrodes</td>
			<td style="width:115px;">Ambu, Copenhagen, Denmark</td>
			<td style="width:119px;">72015-K10</td>
			<td style="width:231px;"></td>
		</tr>
		<tr height="63">
			<td height="63" style="height:63px;width:216px;">3.0T TIM Trio MRI system</td>
			<td style="width:115px;">Siemens AB, Erlangen, GERMANY</td>
			<td style="width:119px;">N/A</td>
			<td style="width:231px;"></td>
		</tr>
		<tr height="84">
			<td height="84" style="height:84px;width:216px;">Asalab amplifier system</td>
			<td style="width:115px;">ANT Neuro, Enschede, NETHERLANDS</td>
			<td style="width:119px;">N/A</td>
			<td style="width:231px;">this system is no longer manufactured and has been deprecated to 64 channel eego EEG amplifier</td>
		</tr>
		<tr height="63">
			<td height="63" style="height:63px;width:216px;">64-channel Waveguard EEG cap, MEG compatible</td>
			<td style="width:115px;">ANT Neuro, Enschede, NETHERLANDS</td>
			<td style="width:119px;">CA-138</td>
			<td style="width:231px;">size Medium</td>
		</tr>
		<tr height="63">
			<td height="63" style="height:63px;width:216px;">Magnetically shielded cordless battery box</td>
			<td style="width:115px;">ANT Neuro, Enschede, NETHERLANDS</td>
			<td style="width:119px;">N/A</td>
			<td style="width:231px;">Magnetic shielding not provided by manufacturer &#8211; Modified by research team</td>
		</tr>
		<tr height="84">
			<td height="84" style="height:84px;width:216px;">OneStep ClearGel Electrode gel</td>
			<td style="width:115px;">H+H Medizinprodukte GbR, Munster, GERMANY</td>
			<td style="width:119px;">154547</td>
			<td style="width:231px;"></td>
		</tr>
		<tr height="63">
			<td height="63" style="height:63px;width:216px;">Akzent Xe Color Anesthesia Machine</td>
			<td style="width:115px;">Stephan GmbH, Gackenbach, GERMANY</td>
			<td style="width:119px;">N/A</td>
			<td style="width:231px;"></td>
		</tr>
		<tr height="63">
			<td height="63" style="height:63px;width:216px;">Omron M6-Comfort Blood Pressure Monitor</td>
			<td style="width:115px;">Omron Healthcare, Kyoto, JAPAN</td>
			<td style="width:119px;">N/A</td>
			<td style="width:231px;"></td>
		</tr>
		<tr height="63">
			<td height="63" style="height:63px;width:216px;">Xenon gas (99.999% purity)</td>
			<td style="width:115px;">Coregas, Thomastown, VIC, AUSTRALIA</td>
			<td style="width:119px;">N/A</td>
			<td style="width:231px;">we estimate that we use approx 40 L (SATP) per participant</td>
		</tr>
		<tr height="63">
			<td height="63" style="height:63px;width:216px;">Medical Nitrous Oxide</td>
			<td style="width:115px;">Coregas, Thomastown, VIC, AUSTRALIA</td>
			<td style="width:119px;">N/A</td>
			<td style="width:231px;">x2 G size cylinders</td>
		</tr>
		<tr height="63">
			<td height="63" style="height:63px;width:216px;">Medical Oxygen</td>
			<td style="width:115px;">Coregas, Thomastown, VIC, AUSTRALIA</td>
			<td style="width:119px;">N/A</td>
			<td style="width:231px;">x2 G size cylinders</td>
		</tr>
		<tr height="63">
			<td height="63" style="height:63px;width:216px;">Medical Air</td>
			<td style="width:115px;">Coregas, Thomastown, VIC, AUSTRALIA</td>
			<td style="width:119px;">N/A</td>
			<td style="width:231px;">x2 G size cylinders</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">Filter Respiratory &#38; HMES with Capno Port Hypnobag</td>
			<td style="width:115px;">Medtronic, MN, USA</td>
			<td style="width:119px;">352/5805</td>
			<td style="width:231px;"></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">Yankauer High Adult</td>
			<td style="width:115px;">Medtronic, MN, USA</td>
			<td style="width:119px;">8888-502005</td>
			<td style="width:231px;"></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">Quadralite EcoMask anaesthetic masks</td>
			<td style="width:115px;">Intersurgical Australia Pty Ltd</td>
			<td style="width:119px;">7093000/7094000</td>
			<td style="width:231px;">size 3 and size 4</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">Suction Canister Disp 1200 mL Medival Guardian</td>
			<td style="width:115px;">Cardinal Health, OH, USA</td>
			<td style="width:119px;">65651-212</td>
			<td style="width:231px;"></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">Catheter Mount Ext 4-13 cm with&#160; 90A elbow</td>
			<td style="width:115px;">Medtronic, MN, USA</td>
			<td style="width:119px;">330/5667</td>
			<td style="width:231px;"></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">Catheter IV Optiva 24g x 19 mm Yellow St Su</td>
			<td style="width:115px;">Smiths Medical, MN, USA</td>
			<td style="width:119px;">5063-INT</td>
			<td style="width:231px;"></td>
		</tr>
		<tr height="63">
			<td height="63" style="height:63px;width:216px;">Dexamethasone Mylan Injection Vials (4 mg/1 mL)</td>
			<td style="width:115px;">Alphapharm Pty Ltd, Sydney, AUSTRALIA</td>
			<td style="width:119px;">400528517</td>
			<td style="width:231px;"></td>
		</tr>
		<tr height="63">
			<td height="63" style="height:63px;width:216px;">Ondasetron (4 mg/2 mL)</td>
			<td style="width:115px;">Alphapharm Pty Ltd, Sydney, AUSTRALIA</td>
			<td style="width:119px;">400008857</td>
			<td style="width:231px;"></td>
		</tr>
		<tr height="546">
			<td height="546" style="height:546px;width:216px;">Medical resuscitation cart</td>
			<td style="width:115px;"></td>
			<td style="width:119px;"></td>
			<td style="width:231px;">The medical resuscitation cart is configured according to the suggested minimal requirements for Adult resuscitation recommended in the document &#34;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.&#160; 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.&#160; Full details can be found at https://resus.org.au/standards-for-resuscitation-clinical-practice-and-education/</td>
		</tr>
		<tr height="63">
			<td height="63" style="height:63px;width:216px;">Maxfilter Version 2.2</td>
			<td style="width:115px;">Elekta Oy, Stockholm, SWEDEN</td>
			<td style="width:119px;">N/A</td>
			<td style="width:231px;">Data analysis software provided with Elekta&#39;s Neuromag TRIUX MEG system</td>
		</tr>
	</tbody>
</table>

recording brain electromagnetic activity during the administration of the gaseous anesthetic agents xenon and nitrous oxide in healthy volunteers

Anæstesi velsagtens giver en af de kun systematiske måder at studere de neurale korrelerer af global bevidsthed/bevidstløshed. Men til dato de fleste neuroimaging eller neurofysiologiske undersøgelser hos mennesker har været begrænset til undersøgelse af γ-Amino-Butyric-Acid-(GABA)-receptor-agonist-based anæstetika, mens virkningerne af dissociative N-Methyl-D-Aspartate-(NMDA)- receptor-antagonist-baserede anæstetika ketamin, lattergas (N2O) og xenon (Xe) er stort set ukendt. I dette dokument beskrives de metoder, der ligger til grund for den samtidige optagelse magnetoencephalography (MEG) og electroencefalografi (EEG) fra sunde mænd under indånding af gasformige bedøvelsesmiddel agenter N2O og Xe. Kombinere MEG og EEG data muliggør vurdering af elektromagnetisk hjerneaktivitet under anæstesi ved høj timelige, og moderat fysisk, opløsning. Her beskriver vi en detaljeret protokol, raffineret over flere indspilninger, der indeholder emnet rekruttering, anæstesi udstyr setup i MEG skanner værelse, dataindsamling og analyse af grundlæggende data. I denne protokol er hver deltager udsat for forskellige niveauer af Xe og N2O i gentagne foranstaltninger cross-over design. Efter relevante baseline optagelser deltagere er udsat til trinvis stigende inspireret koncentrationer af Xe og N2O af 8, 16, 24 og 42%, og 16, 32 og 47% henholdsvis, hvori deres niveau af lydhørhed er sporet med en auditiv løbende ydelse opgave (aCPT). Resultaterne bliver præsenteret for en række optagelser til at fremhæve egenskaberne sensor-niveau af de rå data, spektrale topografi, minimering af hovedbevægelser og utvetydige niveau afhænger af virkningerne på de auditive evoked svar. Dette paradigme beskriver en generel tilgang til registrering af elektromagnetiske signaler tilknyttet aktion af forskellige former for gasformige anæstetika, som let kan tilpasses til brug med flygtige og intravenøs bedøvelsesmiddel agenter. Det forventes, at metoden beskrevet kan bidrage til forståelsen af makro-skala mekanismerne af anæstesi ved at aktivere metodologiske extensions der involverer kilde plads imaging og funktionelle netværksanalyse.

I dette afsnit benytter data indhentet fra et emne for at påvise de typiske træk ved de samtidige optagelser og potentialet i sådanne oplysninger at bidrage en bedre forståelse af anæstesi induceret ændrede bevidsthedstilstande. For at forenkle redegørelsen, resultaterne vises for i) optagelser af anti-brækmiddel administration Oprindelig plan (Oprindelig 3), ii) 0,75 equi-MAC-vågen peak gas koncentrationer (niveau 3) af N2O (47%) og Xe (24%) og iii) Xe peak koncentrat...

Watch this Scientific Journal Video about Recording Brain Electromagnetic Activity During the Administration of the Gaseous Anesthetic Agents Xenon and Nitrous Oxide in Healthy Volunteers at JoVE.com

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

Samtidige magnetoencephalography og electroencefalografi giver et nyttigt værktøj til at søge efter fælles og forskellige makro-skala mekanismer til reduktioner i bevidsthed induceret af forskellige anæstetika. Dette dokument illustrerer de empiriske metoder underliggende optagelse af sådanne data fra raske mennesker under N-Methyl-D-Aspartate-(NMDA)-receptor-antagonist-based anæstesi under indånding af lattergas og xenon.

Optagelse elektromagnetisk hjerneaktivitet under Administration af gasformige bedøvelsesmiddel agenter Xenon og nitrøse oxid i raske frivillige

Anesthesia arguably provides one of the only systematic ways to study the neural correlates of global consciousness/unconsciousness. However to date most ...

The purpose of this experiment is to characterize changes in brain electromagnetic activity in response to the administration of the two gaseous dissociative agents xenon and nitrous oxide to healthy participants in a two-way repeated measures crossover design. Due to the complexity of the experiment, it is important that the majority of equipment setup occurs before participant arrival. The most important of these is the configuration of the EEG system in the magnetically shielded room or MSR.The EEG amplifier is placed in the MSR as far as practical away from the participant, and needs to be configured to run on DC power using either a built-in battery or an external shielded battery box. Fiber optic coupling from the amplifier to the data-logging computer should be checked to be operational. Finally, a video camera in the MSR should be configured such that its field of view clearly captures the participant's face and upper thorax such that the physician anesthesiologist can clearly monitor the respiratory and airway status of the participant.In order that consistent and comparable data is acquired, participants are first interviewed to confirm their eligibility for the study. Participants should be healthy males of 20 to 40 years of age with no psychiatric or neurological conditions, no recent history of drug or alcohol use, and have no respiratory or cardiac conditions. Participants should arrive clean-shaven on the day of the experiment, and having fasted for at least six hours.To ensure high quality EEG recordings, it is recommended that the subject's hair has been recently washed without conditioner, and that their scalp has been firmly brushed to remove any dried or dead skin. An MEG-compatible high-density EEG cap is applied with the appropriate use of conductive gel. Head position indicator coils are then firmly attached at predefined locations on the EEG cap.All auxiliary biopotential electrodes are then applied at the designated locations on the subject's face and body. For subsequent analysis, it is important that all electrodes and HPI coil positions are accurately registered along with digitization of the outlines of the orbits, nasal ridge and cheeks for subsequent coregistration with structural MRI. Two electrodes are placed submentally to record resting muscle tone.Electrooculogram or EOG recordings are made by placing two further electrodes above and below the eye. And finally, a three-lead ECG derivation is configured by electrodes on the left and right wrist flexor surfaces. EEG electrode impedances should then be verified as being below five kiloohms in order to yield high-fidelity recordings.The duration of the experiment as well as the sedative effects of the administered gases makes minimization of head movement vital. A memory foam head brace is applied in order to reduce lateral head movement, and a jute harness is tied around the body to minimize any vertical movement. Eyes-closed resting state and baseline auditory continuous performance task recordings are now performed.It is of vital importance that the administration of anesthetic gases is supervised by a physician anesthesiologist at all times. As well as patient monitoring, the role of the physician anesthesiologist includes ensuring the adequate configuration of the anesthetic gas delivery unit, specialized in this case to deliver and monitor xenon. The physician anesthesiologist will test the anesthesia machine, check that the mask fits comfortably and does not leak, adjust gas flows, insert a cannula, administer antiemetics, as well as commencing denitrogenation with 100%oxygen with the participant seated in the MSR before the final post-antiemetic baseline data collection and the start of the gas administration protocol.At this stage the participant will be comfortably seated in the MSR having been denitrogenated and having been administered dexamethasone and ondansetron to minimize the risk of any adverse nausea or vomiting due to gas administration. Before the MSR door is closed, the anesthetic nurse or other suitably trained medical professional is seated next to the participant. A final check is made that the blood pressure cuff is connected, the button response boxes are comfortably positioned, and the pulse oximeter on the toe or finger is securely fastened.The protocol then proceeds to deliver four Equi-MAC awake progressively increasing stepwise levels of xenon gas, or three stepwise nitrous oxide levels over a period of 15 minutes each in order to assure blood-brain-gas equilibration. Each level should contain a five-minute steady state when the desired gas concentration is reached and should be followed by a 10-minute washout period. During all levels, oxygen, carbon dioxide, and xenon or nitrous oxide levels are continuously monitored and electronically logged.At the end of each level, participants are briefly assessed before progressing to higher levels. Because at the highest xenon level, in which loss of responsiveness is achieved, airway obstruction can readily and unexpectedly occur, and subjects need to be closely monitored and continuously assessed by qualified personnel, both inside and outside the MSR for all necessary action to be taken immediately. At the conclusion of the experiment, the physician anesthesiologist will enter the MSR and debrief with the patient.The participant is then brought outside the MSR where the apparatus is removed and they are administered standard postoperative anesthetic care. Before the participant leaves, ensure they are safe to travel home with a relative or friend. In the next 24 hours, the participant will be required to fill in the questionnaires regarding the procedure and any after effects.This video has been primarily prepared to illustrate the methods involved in delivering gaseous anesthesia while recording simultaneous EEG and MEG data, therefore, only very basic data analysis and representative results are presented to give the viewer a clear idea of what the recorded data should look like. The basic results illustrate examples of head movement, gas concentration timecourse and auditory task accuracy;filtered artifact-free EEG and MEG data;EEG and MEG spectra and power topography;and auditory evoked responses for both baseline and during gas administration. To create the basic results, the following pipeline is employed using a combination of data analysis software platforms and toolboxes.The raw MEG and EEG data is stored as fif and cnt file formats respectively. Head movements are computed using the MaxFilter software and a script written by the authors, both used to convert head movements from the cortonian space into Cartesian coordinates. Auditory task accuracy and reaction time are then computed and visualized, time-aligned with the head movement and gas concentration time series, in order to assess data quality before further processing the EEG and MEG data.Time alignment of the data is based on recorded trigger times. Typically, head movement will be minimal during baseline conditions, while more movement tends to occur at the higher gas levels associated with more dissociated or sedated states. This can be seen here for example in the 42%xenon recording where the top figure shows head movement, and the bottom, gas concentration and auditory task accuracy.Note that loss of responsiveness occurs between 7.5 and 12.5 minutes. Absolute head movement of less than five millimeters is considered acceptable for source imaging purposes. Data segments with movement larger than five millimeters are ignored.Preprocessing of the MEG and EEG data initially involves selection of bad channels. This is followed by the use of the tSSS algorithm to remove artifacts from the MEG recording due to external sources. The rest of the processing pipeline involves the use of data analysis software platforms and associated toolboxes for analysis.Band-pass and notch filtering is applied to both the MEG and EEG data to focus analysis on the frequency band of interest. Time periods in the data containing artifacts are rejected based on visual inspection, in addition to removing periods involving excessive head movement changes. Filtered artifact-free MEG and EEG data can then be visualized and related to anesthetic-induced changes.Amplitude spectra for each sensor and spectral band power topographies across all sensors are then computed for both MEG and EEG data. Visualization of the amplitude spectra at different sensor locations facilitates observation of the effects of different anesthetic levels on signal spectra. Visualization of sensor level power topography in different frequency bands, in this case the alpha band, enables the observation of the effects of different anesthetic levels on the spacial pattern of activity.The filtered artifact-free MEG and EEG data are then epoched using triggers linked to the time of auditory tone delivery. Average auditory evoked responses are then constructed through time on sample averaging. Visualization of sensor level auditory evoked responses allows for the characterization of the effects of anesthetics on the brain's responsiveness.In particular, awakening of the initial evoked response and the disappearance of the later evoked response peaks results from high gas concentrations. There are many other potential interesting analysis steps that can be performed subsequent to this basic analysis. Given that there are many options presented in the literature, we do not cover them in detail here.Such options include MEG and EEG source imaging using beamforming or minimum-norm estimation to gain a better understanding of the relationship between brain activity and brain anatomy. Sensor or source-level functional connectivity analysis can unravel changes in brain networks linked to anesthetic action. There is also the option to either focus analysis on the sensor or source-level auditory evoked responses, or to look at continuous data independent of the auditory stimulus in order to identify any anesthetic-induced changes in global brain dynamics.The macroscale mechanisms of anesthetic-induced reductions in consciousness are not well understood. Evidence from literature has strongly implicated a breakdown in functional connectivity underlying anesthetic-induced reductions in consciousness. Although anesthetics have a diverse range of molecular targets of action and different macroscopic effects on the EEG and MEG, it is still not resolved if there exists a universal or common macroscale mechanism across all anesthetics.Here we have outlined a protocol for performing gaseous anesthesia using the putative NMDA receptor antagonists xenon and nitrous oxide while simultaneously recording MEG and EEG data. This method will facilitate the study of different gaseous and volatile agents on simultaneously recorded MEG and EEG data, and thus the search for universal mechanisms of anesthetic-induced reductions in consciousness.

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