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

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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

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.
ORCID iD: 0000-0002-7977-8100
SPIN-code: 9237-2027

Russian Federation, 4, Timakov street, Novosibirsk, 630117


Aleksandr. N. Khabarov

Scientific Research Institute of Physiology and Basic Medicine

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

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

ORCID iD: 0000-0002-5146-0096
SPIN-code: 6791-7686

Russian Federation, 4, Timakov street, Novosibirsk, 630117

  1. Esencan E, Yuksel S, Tosun YB, et al. XENON in medical area: emphasis on neuroprotection in hypoxia and anesthesia. Med Gas Res. 2013;3(1):4. doi: 10.1186/2045-9912-3-4.
  2. Schmaal L, Hibar DP, Sämann PG, et al. Cortical abnormalities in adults and adolescents with major depression based on brain scans from 20 cohorts worldwide in the ENIGMA Major Depressive Disorder Working Group. Mol Psychiatry. 2017;22(6):900–909. doi: 10.1038/mp.2016.60.
  3. Holl K, Samii M, Gaab MR, et al. EEG changes during five minutes of inhalation of a 33% xenon-O2 mixture. Neurosurg Rev. 1987;10(4):309–310. doi: 10.1007/BF017819575.
  4. Meloni EG, Gillis TE, Manoukian J, Kaufman MJ. Xenon impairs reconsolidation of fear memories in a rat model of post-traumatic stress disorder (PTSD). PLoS One. 2014;9(8):e106189. doi: 10.1371/journal.pone.0106189.
  5. Aftanas L, Akhmetova O, Brack I, et al. Xenon in sub-anesthetic doses for treatment of major depression: a proof-of-concept placebo-controlled pilot study. Biological Psychiatry. 2017;81(10):319–320. doi: 10.1016/j.biopsych.2017.02.854.
  6. Цыганков Б.Д., Шамов С.А., Рыхлецкий П.З., Давлетов Л.А. Возможности применения ксенона в комплексной терапии психопатологических расстройств у больных наркологического профиля // Российский медицинский журнал. ― 2013. ― №4. ― С. 11−14. [Tzigankov BD, Shamov SA, Rykhletskiy PZ, Davletov LA. The possibilities of Xenon application in complex therapy of psycho-pathologic disorders in patients of narcologic profile. Russian medical journal. 2013;(4):11−14. (In Russ).]
  7. Angelakis E, Lubar JF, Stathopoulou S. Electroencephalographic peak alpha frequency correlates of cognitive traits. Neurosci Lett. 2004;371(1):60–63. doi: 0.1016/j.neulet.2004.08.041.
  8. Mierau A, Klimesch W, Lefebvre J. State-dependent alpha peak frequency shifts: Experimental evidence, potential mechanisms and functional implications. Neuroscience. 2017;360:146–154. doi: 10.1016/j.neuroscience.2017.07.037.
  9. Grandy TH, Werkle-Bergner M, Chicherio C, et al. Individual alpha peak frequency is related to latent factors of general cognitive abilities. Neuroimage. 2013;79:10–18. doi: 10.1016/j.neuroimage.2013.04.059.
  10. Базанова О.М. Вариабельность и воспроизводимость индивидуальной частоты альфа-ритма ЭЭГ в зависимости от экспериментальных условий // Журнал высшей нервной деятельности им. И.П. Павлова. ― 2011. ― Т.61. ― №1. ― С. 102–111. [Bazanova OM. Variabel’nost’ i vosproizvodimost’ individual’noy chastoty al’fa-ritma EEG v zavisimosti ot eksperimental’nykh usloviy. Zh Vyssh Nerv Deiat im I P Pavlova. 2011;61(1):102−111. (In Russ).]
  11. Афтанас Л.И., Тумялис А.В, Индивидуальная частота альфа-осцилляций ЭЭГ как нейрофизиологический эндофенотип эмоциональных предиспозиций // Вестник РАМН. ― 2013. ― Т.68. ― №12. ― С. 69−79. [Aftanas LI, Tumialis AV. Individual alpha frequency EEG as neurophysiological endophenotype of affective predispositions. Annals of the Russian Academy of Medical Sciences. 2013;68(12):69−79. (In Russ).]
  12. Bazanova OM, Aftanas LI. Individual measures of electroencephalogram alpha activity and non-verbal creativity. Neurosci Behav Physiol. 2008;38(3):227–235. doi: 10.1007/s11055-008-0034-y.
  13. Kostyunina MB, Kulikov MA. Frequency characteristics of EEG spectra in the emotions. Neurosci Behav Physiol. 1996;26(4):340–343. doi: 10.1007/bf02359037.
  14. Saggar M, King BG, Zanesco AP, et al. Intensive training induces longitudinal changes in meditation state-related EEG oscillatory activity. Front Hum Neurosci. 2012;6:256. doi: 10.3389/fnhum.2012.00256.
  15. Tsuda N, Hayashi K, Hagihira S, Sawa T. Ketamine, an NMDA-antagonist, increases the oscillatory frequencies of alpha-peaks on the electroencephalographic power spectrum. Acta Anaesthesiol Scand. 2007;51(4):472–481. doi: 10.1111/j.1399-6576.2006.01246.x.
  16. Peled S, Jolesz FA, Tseng CH, et al. Determinants of tissue delivery for 129Xe magnetic resonance in humans. Magn Reson Med. 1996;36(3):340–344. doi: 10.1002/mrm.1910360303.
  17. Aftanas LI, Reva NV, Savotina LN, Makhnev VP. Neurophysiological correlates of induced discrete emotions in humans: an individually oriented analysis. Neurosci Behav Physiol. 2006;36(2):119–130. doi: 10.1007/s11055-005-0170-6.
  18. Tugade MM, Shiota MN, Kirby LD. Handbook of positive emotions. New York, NY: Guilford Press; 2014. 527 p.
  19. Arns M, Gordon E, Boutros NN. EEG abnormalities are associated with poorer depressive symptom outcomes with escitalopram and venlafaxine-xr, but not sertraline: results from the multicenter randomized iSPOT-D study. Clin EEG Neurosci. 2017;48(1):33–40. doi: 10.1177/1550059415621435.
  20. Bazanova OM, Mernaya EM, Shtark MB. Biofeedback in psychomotor training. Electrophysiological basis. Neurosci Behav Physiol. 2009;39(5):437–447. doi: 10.1007/s11055-009-9157-z.
  21. Haegens S, Cousijn H, Wallis G, et al. Inter- and intra-individual variability in alpha peak frequency. Neuroimage. 2014;92:46–55. doi: 10.1016/j.neuroimage.2014.01.049.
  22. Lopes da Silva F. Neural mechanisms underlying brain waves: from neural membranes to networks. Electroencephalogr Clin Neurophysiol. 1991;79(2):81–93. doi: 10.1016/0013-4694(91)90044-5.
  23. Berridge MJ. Neuronal calcium signaling. Neuron. 1998;21(1):13–26. doi: 10.1016/S0896-6273(00)80510-3.
  24. Cain SM, Snutch TP. T-type calcium channels in burst-firing, network synchrony, and epilepsy. Biochim Biophys Acta. 2013;1828(7):1572–1578. doi: 10.1016/j.bbamem.2012.07.028.
  25. Destexhe A, Sejnowski TJ. Interactions between membrane conductance underlying thalamocortical slow-wave oscillations. Physiol Rev. 2003; 83(4):1401-1453. doi: 10.1152/physrev.00012.2003.
  26. Bazanova OM, Vernon D. Interpreting EEG alpha activity. Neurosci Biobehav Rev. 2014;44:94-110. doi: 10.1016/j.neubiorev.2013.05.007.
  27. Hardingham G.E., Bading H. Synaptic versus extrasynaptic NMDA receptor signalling: implications for neurodegenerative disorders. Nat. Rev. Neurosci. 2010;11(10):682–696. doi: 10.1038/nrn2911

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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