An Electroencephalogram Metric of Temporal Complexity Tracks Psychometric Impairment Caused by Low-dose Nitrous Oxide

Vrijdag, Xavier C. E.; Waart, Hanna van; Mitchell, Simon J; Sleigh, Jamie

doi:10.1097/aln.0000000000003628

Cited by 13 publications

(20 citation statements)

References 47 publications

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“…Our study found a non‐dose‐dependent decrease in DMN temporal complexity, which was similar in magnitude to the reduction caused by 30% end‐tidal nitrous oxide (Vrijdag et al, 2021). Nitrous oxide is known to increase the excitability of the brain (Hirota, 2006).…”

Section: Discussionsupporting

confidence: 87%

“…The study protocol was approved by the Health and Disability Ethics Committee, Auckland, New Zealand (reference 16/NTA/93), and was registered with the Australian New Zealand Clinical Trial Registry (ANZCTR: U1111‐1181‐9722, http://www.anzctr.org.au/, RRID:SCR_002967). The sample size was based on similar studies previously published (Biersner et al, 1977; Fowler et al, 1983; Hamilton et al, 1992; Vrijdag et al, 2021).…”

Section: Methodsmentioning

confidence: 99%

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Does hyperbaric oxygen cause narcosis or hyperexcitability? A quantitative EEG analysis

Vrijdag

Waart

Sames

et al. 2022

Physiological Reports

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Divers breathe higher partial pressures of oxygen at depth than at the surface. The literature and diving community are divided on whether or not oxygen is narcotic. Conversely, hyperbaric oxygen may induce dose‐dependent cerebral hyperexcitability. This study evaluated whether hyperbaric oxygen causes similar narcotic effects to nitrogen, and investigated oxygen's hyperexcitability effect. Twelve human participants breathed “normobaric” air and 100% oxygen, and “hyperbaric” 100% oxygen at 142 and 284 kPa, while psychometric performance, electroencephalography (EEG), and task load perception were measured. EEG was analyzed with functional connectivity and temporal complexity algorithms. The spatial functional connectivity, estimated using mutual information, was summarized with the global efficiency network measure. Temporal complexity was calculated with a “default‐mode‐network (DMN) complexity” algorithm. Hyperbaric oxygen‐breathing caused no change in EEG global efficiency or in the psychometric test. However, oxygen caused a significant reduction of DMN complexity and a reduction in task load perception. Hyperbaric oxygen did not cause the same changes in EEG global efficiency seen with hyperbaric air, which likely related to a narcotic effect of nitrogen. Hyperbaric oxygen seemed to disturb the time evolution of EEG patterns that could be taken as evidence of early oxygen‐induced cortical hyperexcitability. These findings suggest that hyperbaric oxygen is not narcotic and will help inform divers' decisions on suitable gas mixtures.

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Section: Discussionsupporting

confidence: 87%

Section: Methodsmentioning

confidence: 99%

Does hyperbaric oxygen cause narcosis or hyperexcitability? A quantitative EEG analysis

Vrijdag

Waart

Sames

et al. 2022

Physiological Reports

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“…The next 50 minutes of nitrous oxide exposure (sedation) were marked by periodically quiescent behavior, gradual decline in prefrontal and parietal acetylcholine levels, and global suppression of EEG complexity that was most pronounced in frontal channel clusters. The topographic distribution of changes in EEG complexity during subanesthetic ketamine and nitrous oxide sedation in our study broadly mirrored recent magnetoencephalographic and EEG data published during ketamine and nitrous oxide administration in humans, 12 , 28 suggesting a comparable dynamic landscape during the administration of dissociative anesthetics in rodents.…”

Section: Discussionsupporting

confidence: 87%

Cortical Acetylcholine Levels Correlate With Neurophysiologic Complexity During Subanesthetic Ketamine and Nitrous Oxide Exposure in Rats

Brito¹,

Li²,

Fields³

et al. 2021

Anesthesia &Amp; Analgesia

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BACKGROUND: Neurophysiologic complexity has been shown to decrease during states characterized by a depressed level of consciousness, such as sleep or anesthesia. Conversely, neurophysiologic complexity is increased during exposure to serotonergic psychedelics or subanesthetic doses of dissociative anesthetics. However, the neurochemical substrates underlying changes in neurophysiologic complexity are poorly characterized. Cortical acetylcholine appears to relate to cortical activation and changes in states of consciousness, but the relationship between cortical acetylcholine and complexity has not been formally studied. We addressed this gap by analyzing simultaneous changes in cortical acetylcholine (prefrontal and parietal) and neurophysiologic complexity before, during, and after subanesthetic ketamine (10 mg/kg/h) or 50% nitrous oxide. METHODS: Under isoflurane anesthesia, adult Sprague Dawley rats (n = 24, 12 male and 12 female) were implanted with stainless-steel electrodes across the cortex to record monopolar electroencephalogram (0.5–175 Hz; 30 channels) and guide canulae in prefrontal and parietal cortices for local microdialysis quantification of acetylcholine levels. One subgroup of these rats was instrumented with a chronic catheter in jugular vein for ketamine infusion (n = 12, 6 male and 6 female). The electroencephalographic data were analyzed to determine subanesthetic ketamine or nitrous oxide–induced changes in Lempel-Ziv complexity and directed frontoparietal connectivity. Changes in complexity and connectivity were analyzed for correlation with concurrent changes in prefrontal and parietal acetylcholine. RESULTS: Subanesthetic ketamine produced sustained increases in normalized Lempel-Ziv complexity (0.5–175 Hz; P < .001) and high gamma frontoparietal connectivity (125–175 Hz; P < .001). This was accompanied by progressive increases in prefrontal (104%; P < .001) and parietal (159%; P < .001) acetylcholine levels that peaked after 50 minutes of infusion. Nitrous oxide induction produced a transient increase in complexity ( P < .05) and high gamma connectivity ( P < .001), which was accompanied by increases ( P < .001) in prefrontal (56%) and parietal (43%) acetylcholine levels. In contrast, the final 50 minutes of nitrous oxide administration were characterized by a decrease in prefrontal (38%; P < .001) and parietal (45%; P < .001) acetylcholine levels, reduced complexity ( P < .001), and comparatively weaker frontoparietal high gamma connectivity ( P < .001). Cortical acetylcholine and complexity were correlated with both subanesthetic ketamine (prefrontal: cluster-weighted marginal correlation [CW r] [144] = 0.42, ...

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“…The remaining epochs for that condition and exposure were stored for further analysis. See Vrijdag et al (2021) for the script 57 .…”

Section: Methodsmentioning

confidence: 99%

EEG functional connectivity is sensitive for nitrogen narcosis at 608 kPa

Vrijdag

Waart

Pullon

et al. 2022

Sci Rep

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Divers commonly breathe air, containing nitrogen. Nitrogen under hyperbaric conditions is a narcotic gas. In dives beyond a notional threshold of 30 m depth (405 kPa) this can cause cognitive impairment, culminating in accidents due to poor decision making. Helium is known to have no narcotic effect. This study explored potential approaches to developing an electroencephalogram (EEG) functional connectivity metric to measure narcosis produced by nitrogen at hyperbaric pressures. Twelve human participants (five female) breathed air and heliox (in random order) at 284 and 608 kPa while recording 32-channel EEG and psychometric function. The degree of spatial functional connectivity, estimated using mutual information, was summarized with global efficiency. Air-breathing at 608 kPa (experienced as mild narcosis) caused a 35% increase in global efficiency compared to surface air-breathing (mean increase = 0.17, 95% CI [0.09–0.25], p = 0.001). Air-breathing at 284 kPa trended in a similar direction. Functional connectivity was modestly associated with psychometric impairment (mixed-effects model r2 = 0.60, receiver-operating-characteristic area, 0.67 [0.51–0.84], p = 0.02). Heliox breathing did not cause a significant change in functional connectivity. In conclusion, functional connectivity increased during hyperbaric air-breathing in a dose-dependent manner, but not while heliox-breathing. This suggests sensitivity to nitrogen narcosis specifically.

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An Electroencephalogram Metric of Temporal Complexity Tracks Psychometric Impairment Caused by Low-dose Nitrous Oxide

Cited by 13 publications

References 47 publications

Does hyperbaric oxygen cause narcosis or hyperexcitability? A quantitative EEG analysis

Does hyperbaric oxygen cause narcosis or hyperexcitability? A quantitative EEG analysis

Cortical Acetylcholine Levels Correlate With Neurophysiologic Complexity During Subanesthetic Ketamine and Nitrous Oxide Exposure in Rats

EEG functional connectivity is sensitive for nitrogen narcosis at 608 kPa

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