Placebo-controlled study of xenon effect on the emotions and frequency of the EEG alpha-oscillations

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Abstract


Background: A partial blocker of N-methyl-D-aspartate (NMDA) receptors, the noble gas Xe in sub-anesthetic (25−50%) doses performs its neuroprotective effects on the brain structures functions through binding to glycine site. According to the single studies, Xe reveals the thymoleptic properties, which are reflected in the strengthening of positive emotional activation and a decreasing ― negative. The purpose of this placebo-controlled pilot study in healthy volunteers was to evaluate the translational potential of Xe as a possible antidepressant.

Methods: In placebo-controlled, double-blind study 14 right-handed healthy volunteers (males, right handed) were randomly assigned to 15 min inhalation session either of an admixture of up to a maximum of 25% Xe (25% Хе/30% О2/45% N2) or placebo (70% N2/30% О2) for 15 min. The inspiratory Xe concentration was titrated during the first 5 min until 25% was achieved and maintained for 5 min. Across the study, we had recorded, ECG, SGR, and 64-channel EEG. As a neurophysiological index of the experienced emotion intensity changes individual alpha peak frequency (iAPF) shift was studied. Changes in intensity of experiencing ten discrete emotions (surprise, joy, happiness, bliss, awe, fear, sadness, anxiety, anger, disgust) as indexed by visual analog scales (VAS) were recorded in pre- and post Xe and placebo inhalation conditions. The research received approval of the institutional ethics committee.

Results: Repeated measures ANOVAs of the emotional reactivity [(GAZ 2: Xe, placebo) × CONDITION (2: pre, post) × EMOTION (10)] and of the iAPF [(GAZ 2: Xe, placebo) × CONDITION: 2 (pre, post) established high significant specific effects of the Xe compared with placebo. The impact of Xe in a sample of examined subjects revealed two types of responses: in one part, an increase in the experiencing positive emotions intensity, accompanied by the rise in iAPF, in the other, insignificant changes in the initial emotional profile with a tendency to decrease in combination with a decrease in iAPF. Thus, in agreement with ad hoc hypothesis, Xe in sub-anesthetic doses induced the enhancement of the positive emotion intensity experience only in those participants who demonstrated the increasing of the iAPF. Correlation and regression analyses revealed a positive correlation of iAPF changes with an intensity of positive emotional activation (increased power of experiencing emotions of joy, happiness, and bliss), as well as the iAPF shift ability to predict the thymoleptic effect of Xe with 74% probability. Additionally, we were able to deduce that individual nature of changes in iAPF and the nature of emotional-reactivity in response to Xe depend on the absolute value of the baseline iAPF.

Conclusions: We had first established that Xe as a blocker of NMDA receptors in sub-anesthetic doses enhances positive emotional activation (increased intensity of experiencing discrete emotions of joy, happiness, and bliss) in healthy volunteers. The presence or absence of the thymoleptic response to Xe varies due to the individual characteristics of the neurophysiological endophenotype of the EEG alpha activity ― iAPF. The obtained data allow us to consider iAPF as a potential neurophysiological endophenotypic predictor of an individual thymoleptic response to Xe in sub-anesthetic doses in the clinic of the affective disorders. To assess the real Xe translational potential, as a clinical thymoleptic and antidepressant agent, it is necessary to perform large-scale placebo-controlled clinical studies in patients with various clinical forms of negative affect pathology.


Lyubomir I. Aftanas

Scientific Research Institute of Physiology and Basic Medicine; Novosibirsk State University

Email: liaftanas@gmail.com
ORCID iD: 0000-0003-3605-5452

Russian Federation, 4, Timakov street, Novosibirsk, 630117; 1, Pirogova street, Novosibirsk, 630090

MD, PhD, Professor

Olga M. Bazanova

Scientific Research Institute of Physiology and Basic Medicine

Author for correspondence.
Email: bazanovaom@physiol.ru
ORCID iD: 0000-0002-7977-8100
SPIN-code: 9237-2027

Russian Federation, 4, Timakov street, Novosibirsk, 630117

PhD

Aleksandr. N. Khabarov

Scientific Research Institute of Physiology and Basic Medicine

Email: bazanova_olgamih@mail.ru
ORCID iD: 0000-0002-7699-8335
SPIN-code: 9831-1368

Russian Federation, 4, Timakov street, Novosibirsk, 630117

научный сотрудник Лаборатории аффективной, когнитивной и трансляционной медицины

Svetlana M. Pustovoit

Scientific Research Institute of Physiology and Basic Medicine

Email: kvurts@gmail.com
ORCID iD: 0000-0003-1239-904X
SPIN-code: 5509-8588

Russian Federation, 4, Timakov street, Novosibirsk, 630117

научный сотрудник лаборатории аффективной, когнитивной и трансляционной нейронауки

Ivan V. Braсk

Scientific Research Institute of Physiology and Basic Medicine

Email: brack@physiol.ru
ORCID iD: 0000-0002-5146-0096
SPIN-code: 6791-7686

Russian Federation, 4, Timakov street, Novosibirsk, 630117

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Supplementary files

Supplementary Files Action
1. Fig. 1. Research procedure View (94KB) Indexing metadata
2. Fig. 2. The intensity of experiencing positive (surprise, happiness, joy, bliss and ecstasy) and negative (fear, anxiety, disgust, sadness and anger) emotions before and after inhaling gas mixtures of Xe and placebo, M ± m View (173KB) Indexing metadata
3. Fig. 3. Grouping according to the median of the distribution of the alpha peak frequency shift (ΔiAPF) in response to Xe inhalation in the study sample (A). ΔiAPF after inhalation Xe and placebo in the formed groups (B), M ± m View (132KB) Indexing metadata
4. Fig. 4. Change in the intensity of experiencing discrete emotions (ΔE) after Xe inhalation in educated groups, M ± m View (81KB) Indexing metadata
5. Fig. 5. The results of the correlation analysis of the relationship between the alpha peak frequency shift (ΔiAPF) and iAPF values before Xe (A) inhalation, the averaged reactivity of experiencing (Δ) positive (B) and Δ-negative (C) emotions after Xe inhalation View (156KB) Indexing metadata
6. рисунок 3 View (64KB) Indexing metadata

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