[Interhemispheric asymmetry of EEG rhythm connections during spontaneous awakenings after short sleep episodes during a monotonous psychomotor test]. / Mezhpolusharnaya asimmetriya svyazei ritmov EEG pri spontannykh probuzhdeniyakh posle kratkovremennykh epizodov sna pri vypolnenii monotonnogo psikhomotornogo testa.

OBJECTIVE: To study interhemispheric asymmetry (IHA) according to electroencephalography (EEG) data of a healthy person during cognitive awakening from the second stage of daytime sleep before restoring the performance of the psychomotor test. MATERIAL AND METHODS: In 23 healthy adult subjects, we studied IHA in the amplitude-amplitude interaction of EEG rhythms for 20 sec segments before spontaneous awakening determined by the moment the alpha-rhythm appearance on the EEG and the subsequent onset of psychomotor activity. The state of the subject during this period (in the initial stage of the so-called cognitive awakening preceding the behavioral awakening), when the person is unable to move, but is able to perceive external stimuli, is an experimental model for highlighting signs of conscious activity of patients when coming out of a coma. Wavelet transform was used to calculate the rhythmic characteristics of bioelectrical activity. The Kendall correlation coefficient served as a measure of rhythm interaction. RESULTS: IHA in the interaction of EEG rhythms is dynamic nature and formed by theta rhythm connections with alpha2- and beta-rhythms in the left brain hemisphere and delta-type connections in the right. CONCLUSION: Possibly, the greater activation of the left hemisphere is related to the retrieval of an instruction from memory, which subsequently allows to return to the activity interrupted by sleep.

[Sleep and neurophysiological correlates of consciousness activation upon awakening]. / Son i neirofiziologicheskie korrelyaty aktivatsii soznaniya pri probuzhdenii.

The authors discuss modern ideas about the neurophysiological mechanisms of awakening from sleep and the results of own EEG studies of the spatio-temporal dynamics of the activity of the cerebral hemispheres using the own experimental model for studying consciousness in the sleep-wake paradigm. This model is based on continuous execution of a monotonous psychomotor test performed lying down with eyes closed and allows observing several short-term sleep episodes during a 1-hour experiment, followed by spontaneous awakening and restoration of the psychomotor test. A necessary condition for the restoration of activity during spontaneous awakening is the emergence of the EEG alpha rhythm, the parameters of which determine the effectiveness of the restoration of the psychomotor test and, accordingly, the achievement of a certain level of consciousness, and therefore can be considered as a neurophysiological correlate of consciousness activation upon awakening. The considered experimental model of consciousness can be useful for analyzing the neurophysiological mechanisms of consciousness activation in patients with chronic impairments of consciousness and for searching for effective methods for the rehabilitation of such patients.

[ Spectrum of oncogene mutations is different in melanoma subtypes].

Melanoma is the most lethal malignancy of skin, which is comprised of clinically relevant molecular subsets defined by specific "driver" mutations in BRAF, NRAS, and KIT genes. Recently, the better results in melanoma treatment were obtained with the mutation-specific inhibitors that have been developed for clinical use and target only patients with particular tumor genotypes. The aim of the study was to characterize the spectrum of "driver" mutations in melanoma subtypes from 137 patients with skin melanoma and 14 patients with mucosal melanoma. In total 151 melanoma cases, the frequency of BRAF, NRAS, KIT, PDGFRA, and KRAS mutations was 55.0, 10.6, 4.0, 0.7, and 0.7%, respectively. BRAF mutations were found in 69% of cutaneous melanoma without UV exposure and in 43% of cutaneous melanoma with chronic UV exposure (p=0.045), rarely in acral and mucosal melanomas. Most of melanomas containing BRAF mutations, V600E (92%) and V600K (6.0%) were potentially sensitive to inhibitors vemurafenib and dabrafenib. NRAS mutations were more common in cutaneous melanoma with chronic UV exposure (26.0%), in acral and mucosal melanomas; the dominant mutations being Q61R/K/L (87.5%). KIT mutations were found in cutaneous melanoma with chronic UV exposure (8.7%) and mucosal one (28.6%), but not in acral melanoma. Most of KIT mutations were identified in exon 11; these tumors being sensitive to tyrosine kinase inhibitors. This is the first monitoring of BRAF, NRAS, KIT, PDGFRA, and KRAS hotspot mutations in different subtypes of melanoma for Russian population. On the base of data obtained, one can suppose that at the molecular level melanomas are heterogeneous tumors that should be tested for "driver" mutations in the each case for evaluation of the potential sensitivity to target therapy. The obtained results were used for treatment of melanoma patients.

[Relationships between the Flexibility of Cognitive Performance and the Response of Alpha-Rhythm in the Go/NoGo Task].

During the experiments, healthy subjects (n = 35) completed Go/NoGo task with a set towards the recognition of negative face expression; the visual stimuli were set in the middle of a 16-second-long interval between target (face) and triggering stimuli. The local changes in low-frequency alpha-oscillations in response to stimuli (desynchronization after a positive Go stimulus and synchronization after an inhibitory NoGo stimulus) take place in posterior frontal and anterior temporal lobes of the left hemisphere, i.e., in cortical areas directly involved in speech processes. In subjects with flexible set towards recognition, we observed synchronization of alpha-rhythm after inhibitory NoGo stimulus; in subjects with more stable set, this did not occur. Thus, we obtained new experimental data confirming that induced synchronization of alpha-oscillations reflects the enhancement of descending inhibitory control of the prefrontal cortex.

[Influence Additional Cognitive Tasks on EEG Beta Rhythm Parameters during Forming and Testing Set to Perception of the Facial Expression].

The research of changes of a beta rhythm parameters on condition of working memory loading by extension of a interstimuli interval between the target and triggering stimuli to 16 sec is investigated on 70 healthy adults in two series of experiments with set to a facial expression. In the second series at the middle of this interval for strengthening of the load was entered the additional cognitive task in the form of conditioning stimuli like Go/NoGo--circles of blue or green color. Data analysis of the research was carried out by means of continuous wavelet-transformation on the basis of "mather" complex Morlet-wavelet in the range of 1-35 Hz. Beta rhythm power was characterized by the mean level, maxima of wavelet-transformation coefficient (WLC) and latent periods of maxima. Introduction of additional cognitive task to pause between the target and triggering stimuli led to essential increase in absolute values of the mean level of beta rhythm WLC and relative sizes of maxima of beta rhythm WLC. In the series of experiments without conditioning stimulus subjects with large number of mistakes (from 6 to 40), i.e. rigid set, in comparison with subjects with small number of mistakes (to 5), i.e. plastic set, at the forming stage were characterized by higher values of the mean level of beta rhythm WLC. Introduction of the conditioning stimuli led to smoothing of intergroup distinctions throughout the experiment.

[Changes of Alpha Cortical Potentials Spatial Synchronization on Value Go/NoGo Stimuli].

At healthy people (n = 35) on model of the cognitive set on an angry face is shown: introduction of positive and negative coordinated stimuli Go/NoGo in the inter-stimuli interval can change considerably the top-down positive and negative influences of prefrontal cortex on the cortical areas participating in a visual perception and by that to influence plasticity of the set. The cortical topography of the top-down influences in response to NoGo is determined by local changes of power of fluctuations of potentials in alpha rhythm range. Changes of spatial synchronization of alpha potentials occurs only in their low-frequency range, depending on the level of plasticity of the set. At its rigid forms coherent communications between prefrontal and other cortical zones it is obviously more expressed in the left hemisphere. Apparently at rigid forms of cognitive activity left-side cortical activation with more essential involvement of speech, semantic functions, plays the compensating role.

[Changes of the alpha-rhythm after introducing stimuli Go/NoGo in the context of experiments with a set to an angry face].

At healthy adults is (n = 35) in the middle of 16 second pauses between target (faces) and starting stimuli conditioning signals Go/NoGo. Lack of essential changes of flexibility of the set after introduction of an additional cognitive task is explained by enhansment of the induced synchronization of an alpha rhythm in time intervals between target, conditioning and starting stimuli. The increase of alpha potentials synchronization reflect the top-down inhibitory control suppressing effect of irrelevant factors, and that facilitating processing of significant information. In the range of time between NoGo and starting stimuli locally in a motor zone of cortex of only the left hemisphere (C3, FC3) the induced synchronization of low-frequency and especially high-frequency alpha rhythm is registered. One more experimental confirmation of the theory on the brake nature of this electrophysiological phenomenon is obtained. Used in physiology of the highest nervous activity of concept about internal or conditional inhibition is considered within the theory of top-down inhibitory control from prefrontal cortex.

[The spatial synchronization and power of the alpha and theta rhythm after action of signals Go/NoGo].

At adult healthy subjects (n = 35) in pause between the target (facial expression) and triggering stimuli showed the conditioning signals of Go/NoGo defining significants of triggering stimulus. The low-frequency alpha rhythm reacts to stimuli Go/NoGo in the left hemisphere more strongly. The coherence of low-frequency alpha potentials on 5-7 second after positive and negative conditioning (Go/NoGo) stimuli increases. Just before the triggering stimulus irrespective of their sign, confirms situation that development of a differentiation demands not less functional activity, than positive conditional reaction. Modulation of cortical activity is connected generally with the talamo-cortical system of selective attention. The coherence a theta rhythm increases after action of positive conditioning signal in the medial cortical areas. It is linked with the function of emotional memory.

[Power of gamma responses to facial expression at eight second interval between the target and trigger stimuli].

Power EEG gamma-band (21-60 Hz) in the process of forming and testing the cognitive set on the face expression is seen in conditions of the model, which provides a higher load on working memory by lengthening the intervals between the target and trigger stimuli to 8 s. The results are compared with data from previous experiments with increased load in the form of additional cognitive tasks, when there was an increase of gamma responses by "success" of the job subjects. In this study, the responses to set-stimuli were observed significant lower (relative to prestimulus period) in all groups of subjects that were treated as inhibition of gamma activity. Significant differences in the levels of power gamma-band between the groups were identified by comparing the set up steps (forming and testing), and frequency-bands. The second important difference is the absence of differences in the dynamics of power patterns gamma2 (41-60 Hz) between groups of subjects depending on the "success" of the job. We present arguments to substantiate the "paradoxical" results in the conditions of use of the plant model.

[Psychophysiological signs of high-flexible forms of set on the emotionally negative facial expression].

In a series of studies of influence of past experience on an recognition of emotionally negative facial expression where obtained experimental facts which we consider as the formation signs of under certain conditions high-plastic cognitive (flexible) sets ("not fixed sets", according to D.N. Uznadze) when there switching or updating was not accompanied by illusory distortion of recognition. The studies of this form of set revealed: 1--the induced reaction of synchronization of a teta-rhythm to target stimulus was larger, than in cases with rigid set; 2--the induced reaction of an alpha rhythm to target stimulus is expressed in its synchronization, at the others cases--in a desynchronization; 3--at increase in a time interval between target and trigger stimuli observe alpha rhythm synchronization in the prestimulus period and in time intervals between them, at other cases it wasn't observed; 4--at children this form of set observed at the age of 10-11 years when "mature" set on an facial expression is formed.

[Beta-rhythm parameters changes during cognitive set to emotional facial expression with supplemented long-time interval between a warning and a target stimulus].

Beta-rhythm parameters during cognitive set to emotional facial expression were investigate in 35 healthy adults. Formation of the set was supplemented long-time interval (8 c) between a warning and a target stimulus. Rhythmical component of EEG were revealed using wavelet functions. Maximum and mean levels of wavelet coefficient (WLC) in the beta-rhythm were analyzed. We obtained 3 groups of subjects depend on mistakes of recognition facial expression. Group with correct recognition had high WLC mean level during the experiment, WLC maxima during first second of inter-stimulus interval, large latency of WLC maxima during the stage forming and predominance level WLC maxima in the left hemisphere. Two groups of subjects with mistakes in recognition had low WLC mean, maxima and their latency during set forming. Right hemisphere (WLC maxima) dominated in these groups.

[Induced synchronization of alpha rhythm in the time intervals between the visual stimuli at different degrees of set flexibility].

In healthy adults (n = 35) was used the model the set study of recognition angry facial expression. The load on working memory by extending the interstimuli time up to 16 sec between the target (facial image) and starting (spot light) stimuli does not lead to a significant slowdown of switching of the set. Differences in the magnitude of the induced synchronization of the alpha rhythm in interstimulus period obtained in the subjects with the change in recognition of emotional facial expressions and the subjects "without errors". At the last group synchronization is clearly more pronounced. The implementation of successive cognitive acts is modulated by selective attention, whichis evident in the level of changes the induced synchronization/desynchronization of alpha range potential. The proposed mechanism "inhibitory control" provides the flexibility of cognitive processes by suppressing effect on cortical processes irrelevant factors during interstimulation pauses. This "protective" mechanism, we believe due to little effect of the loading on working memory.

[Changes of the l and upper alpha frequency oscillating during time intervals between meaningful visual stimuli].

In healthy adults (n = 35) was used the model of the cognitive set to emotionally negative facial expression ("angry face"). In order to load the working memory was lengthened the time interval between target (face) and trigger stimuli. In cases of the flexible set (no errors in recognition of facial expression was accompanied switching or updating the set) the induced high frequency alpha oscillations (10.5-13 Hz) were more pronounced than in subjects with the rigid set (six and more errors). The role of the "top-down cognitive control" in providing flexible form of cognitive sets are discussed.

[Additional memory load causes changes in induced EEG beta-rhythm in experiments with a visual set formed to facial expression].

Subjects were divided into two equal groups 35 healthy subjects each. Formation of the visual set to facial emotion recognition was supplemented with two types of additional task: either visuospatial (to find a target stimulus among others) or verbal (to tell a word from a pseudoword). The results of the experiments were compared to those obtained in similar experiments without the memory load. Changes in the EEG beta rhythm during visual set forming and testing were studied. The EEG was analyzed by wavelet transformation. Changes in the mean level, maximum and latency of the maximum of wavelet coefficient were rated at different stages of the experiment. All these characteristics for the beta rhythm were higher in experiments with both types of additional memory load as compared to those without the memory load.

[Dynamics of induced EEG in the intervals between a target and trigger stimuli during formation of a set to emotionally negative facial expression].

A visual set was used as a model to study the influence of the increased memory load on the recognition of facial expression in 70 healthy adults. In order to additionally load the working memory, we lengthened the time gap between target (faces) and trigger stimuli. Such a lengthening from 1 to 8 s resulted in an increase of set plasticity (fewer mistakes in facial expression recognition). It also led to a reduction of the reaction time and less number of contrast illusions in recognition. We analyzed theta- and alpha-band EEG changes during individual segments of the time gap and suggested that repeated trials with a certain fixed interval between stimuli formed an inner representation of the interval duration. This inner representation up-regulates the visual attention in case of anticipation of a relevant event (stimulus) and down-regulates the attention when the stimulus is not expected. In case of the plastic set, the induced EEG synchronization in the alpha band is stronger in the trials with correct recognition in the middle of the inter-stimulus time gap. We think this synchronization reflects the action of the top-down cognitive control that suppresses the influence of irrelevant information on the brain activity. Theta-band dynamics in the inter-stimulus time gap can be associated with the emotional strain caused by the fact that a person had to retain in memory (for several seconds) the result of facial expression recognition.

[Development of function of the recognition of angry face expression in children of 5-11 years old].

At children 5-6, 7-8 and 10-11 years on model of cognitive set are revealed age features of influence of last experience on perception of a face expression. At children of 5-6 years rigid set on an angry face was experimentally formed: at a testing stage show set-shifting caused large number of erroneous recognition of face expression of perseverative type (assimilative illusions). Plasticity of the set raises in 7-8-year age and considerably the number of assimilative illusions decreases. On 10-11 years sets doesn't differ essentially from adult people on plasticity and a ratio of number of assimilative and contrast illusions. Changes of spatial synchronization of electric potentials teta- and alpha ranges of frequencies in all age groups it is observed generally at a stage of formation of set. On all age groups strong correlation between bioelectric data and features of the set on a face expression is revealed. These data supports the hypothesis that cortiko-hippocampal and fronto-thalamic functional systems of integration of a brain activity participate in the organization of a set on an emotional face expression and provide cognitive flexibility.

[Changes in the spatial synchronization of neocortical potentials in interstimulus intervals during formation of a set to emotionally negative facial expression].

The model of cognitive set to emotionally negative facial expression was used in the study (35 young healthy subjects) of EEG events in a 8-second interval between the target and triggering stimuli. Coherence of brain potentials recorded from different cortical areas of the right and left brain hemispheres in the alpha and theta bands was analyzed in time segments within pre- and poststimulus intervals. A certain dynamics in the spatial synchronization in the alpha-band was revealed, which might reflect modulation of selective attention in time periods of the cognitive process providing its plasticity and set shift in response to a change in the situation. It is suggested that the source of attention modulation is the inner representation of the intervals between significant stimuli formed in the prefrontal cortex as a result of learning. Analysis of changes in the spatial synchronization in the theta band at individual stages of the set to angry face suggests that the corticohippocampal system is not directly involved in the time interval estimation but is linked to the emotional memory.

[Cognitive control in recognition of emotionally negative face in 5-10-year-old children].

We used the experimental model of cognitive visual set, designed by D.N. Uznadze, to study the influence of previous experience on emotional face expression recognition in pre-school (6.1 +/- 0.3 years) and elementary school (10.5 +/- 0.1 years) children. Our results suggest that the ability to form a cognitive set to an angry face expression develops in ontogenesis in strong concordance with functional maturation of prefrontal cortex that takes place at the age of approximately 10 years. At this age children display almost the same level of set plasticity and a similar kind of erroneous perceptions during set actualization as grown-ups. Children of younger age (6.1 +/- 0.3 years) display more perceverative erroneous perceptions, or assimilative illusions (probably of a priming origin), than the above mentioned groups. We consider this to be a result of a more strong influence of previous experience in their case.

[Changes in face expression recognition caused by additional visual-spatial load].

Changes in face expression recognition and EEG synchronization arising from additional load on working memory were studied in healthy adults. Two types of additional task--semantic and visuospatial--were used to load working memory in an experiment with a visual set, formed to facial stimuli. During perception of new facial stimuli, both these types of additional task caused an increase of erroneous face expression recognitions in the form of assimilative illusions. Alpha-band (8-10 Hz) EEG synchronization analysis revealed that additional memory load causes a decrease of frontal attention system input in set-forming and set-shifting. As for theta-band (4-7 Hz) synchronization, it changed ambiguously at additional memory load--in right fronto-temporal region coherence function decreased; other coherence connections, especially intra-hemispheric and in the left hemisphere, increased. At issue is the crucial role of fronto-thalamic and cortico-hippocampal systems in plasticity of visual sets formed to facial expressions.

[Induced synchronization/desynchronization of the theta and alpha cortical electrical activity to a face stimuli with increasing visual working memory load].

Using a cognitive set to emotional facial expression as a model, induced synchronization/desynchronization of the cortical theta- and alpha-activities were studied in adult healthy people under conditions of increased load on the working memory (additional task of the verbal stimuli recognition). A correlation was found between behavioral (increase in the set rigidity) and electrophysiological (decrease of the induced theta-rhythm synchronization) data. A hypothesis is suggested that the earlier revealed increase in the tonic prestimulus theta-activity and suppression of the poststimulus phasic activation of the cortico-hippocampal system are one of the mechanisms of the decrease in plasticity of the cognitive function of the emotional facial expression recognition under conditions of the increased load on the working memory. Reciprocal relations between two functional systems of the brain activity integration (cortico-hippocampal and fronto-thalamic) in the process of recognition of emotional facial expression are discussed.