Плацебо-контролируемое исследование влияния ксенона на эмоции и частоту альфа-осцилляций у человека

Background: A partial blocker of N-methyl-D-aspartate (NMDA) receptors, the noble gas Xe in sub-anesthetic (2550%) 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.Обоснование. Частичный блокатор NMDA-рецепторов благородный газ ксенона в субанестетических концентрациях обнаруживает свойства тимолептика. Цель исследования ― оценка трансляционного потенциала Xe как возможного антидепрессанта. Методы. В исследовании 19 здоровым добровольцам проводили 15-минутные сеансы ингаляции ксеноновой газовой смеси Xe (25% Хе/30% О2 /45% N2 ) и плацебо (70% N2 /30% О2 ) с одновременной регистрацией 64-канальной электроэнцефалограммы (ЭЭГ). Для оценки динамики эмоциональной активации в ответ на Xe и плацебо использовали показатели зрительных аналоговых шкал интенсивности переживания 10 дискретных эмоций и индивидуальную частоту альфа-ритма ЭЭГ (individual alpha peak frequency, iAPF). Результаты. Хе по сравнению с плацебо вызывал два типа ответов: у одной части испытуемых ― усиление положительной эмоциональной активации, сопровождающейся ростом iAPF, у другой ― незначимые изменения исходного эмоционального фона в сочетании со снижением iAPF. Регрессионный анализ обнаружил положительную взаимосвязь изменений iAPF с выраженностью положительной эмоциональной активации и способность сдвига iAPF предсказывать тимолептический эффект Xe. Характер эмоциональной реактивности и изменений iAPF в ответ на Xe зависит от абсолютной величины фоновой iAPF. Заключение. Впервые установлено, что Xe у здоровых добровольцев в субанестетических дозах усиливает положительную эмоциональную активацию. Ответ на Xe варьирует в связи с индивидуальными особенностями нейрофизиологического эндофенотипа альфа-активности ЭЭГ ― iAPF. Полученные данные позволяют рассматривать iAPF в качестве потенциального нейрофизиологического предиктора индивидуального тимолептического ответа на Xe. Необходимо выполнить масштабное плацебоконтролируемое клиническое исследование на пациентах с патологиями негативного аффекта для оценки реального трансляционного потенциала Xe как клинического тимолептика и антидепрессанта

Interpreting EEG alpha activity

Exploring EEG alpha oscillations has generated considerable interest, in particular with regards to the role they play in cognitive, psychomotor, psycho-emotional and physiological aspects of human life. However, there is no clearly agreed upon definition of what constitutes ‘alpha activity’ or which of the many indices should be used to characterize it. To address these issues this review attempts to delineate EEG alpha-activity, its physical, molecular and morphological nature, and examine the following indices: (1) the individual alpha peak frequency; (2) activation magnitude, as measured by alpha amplitude suppression across the individual alpha bandwidth in response to eyes opening, and (3) alpha “auto-rhythmicity” indices: which include intra-spindle amplitude variability, spindle length and steepness. Throughout, the article offers a number of suggestions regarding the mechanism(s) of alpha activity related to inter and intra-individual variability. In addition, it provides some insights into the various psychophysiological indices of alpha activity and highlights their role in optimal functioning and behavior

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical science. © The Author(s) 2019. Published by Oxford University Press