Physiological Support of Goal-Directed Activity in Human.

The effectiveness of goal-directed human behavior and the processes underlying organization of such activity are the subjects of various biomedical studies. Here we review both classical and modern evidence on the fundamental principles of goal-directed human activity. Facts are presented about the basic mechanisms that ensure the effectiveness of goal-directed behavior and determine its physiological cost.

Formation of Different Strategies of Competitive Foraging Behavior in Rats.

We studied competitive interactions of rats during instrumental foraging behavior. Two groups of animals were revealed: rats with predominance of operant actions for getting food reinforcements (donors) and kleptoparasites that more often get food after instrumental acts of the partners. Intergroup differences began to appear and increased from 3-4 paired experiments. It was revealed that at the individual stage of learning the instrumental skill, donor rats were faster in learning and showed high foraging activity with shorter latency in comparison with kleptoparasites, which were initially slower and performed a large number of inter-signal actions in the form of unconditioned peeking into the feeder.

Behavior of In Utero Stressed Rats in the Elevated Plus Maze Test during Different Periods of Postnatal Ontogeny.

We studied the effect of prenatal stress (dams were forced to swim in cold water (10°C; 5 min) from day 10 to 16 of gestation) on the behavioral parameters of the offspring in an elevated plus maze on days 21, 30, and 60 of life (suckling, infantile, and juvenile ages, respectively). Females at the suckling age demonstrated suppressed orientation and exploratory activity and increased anxiety, which returned to normal by the infantile and juvenile periods. Prenatally stressed males in juvenile age were characterized by reduced anxiety (assessed by the time spent in the closed and open arms of the plus maze). Thus, the effect of prenatal stress on the behavioral parameters manifested differently depending on the sex and stage of postnatal ontogeny. The modulatory effects of prenatal stress on the analyzed behavioral parameters were more pronounced in females at early stages of postnatal ontogeny (suckling and infantile ages).

Correlation between Cognitive Performance and Interhemispheric Asymmetry of EEG Alpha Rhythm during Lateralized Presentation of Visual Information against the Background of Optical Stimulation.

The effect of lateralized optical stimulation with a frequency of 10 Hz on the effectiveness of cognitive task performance (n-back test) was studied in 33 healthy subjects (right-handed men). Test visual information was presented to the right or left visual hemifield under normal conditions and against the background of optical stimulation with a frequency of 10 Hz. The absolute values of the spectral power of the high (10-13 Hz) subrange of alpha-rhythm of EEG (SPα2) were calculated. When test information was sent to the right hemisphere against the background of stimulation, an increase in task performance was revealed in subjects with low SPα2. This was accompanied by an increase in SPα2 in some cortical areas of the contralateral (left) hemisphere and, as a result, an increase in left-side dominance of SPα2. The findings indicate the possibility of using lateralized optical stimulation to improve cognitive task performance, in particular, by changing the interhemispheric asymmetry of the EEG alpha2-rhythm.

Structure of the Useful Adaptive Result in the Systemic Organization of Physiological Functions as a Subject of Scientific Analysis: History and Prospects of Research.

The concept of "useful adaptive result", a key concept in the theory of functional systems by P. K. Anokhin, is discussed. A large body of works devoted to this problem, in the historical aspect and on the basis of results of own researches, allows concluding that useful adaptive results of the system organization of physiological functions include not only the event arising as a result of activity of the system, but also the physiological cost of this activity. The ratio of the physiological cost and performance indicators gives an idea of the effectiveness of system activity and is its integral characteristic. The main approaches to estimation of physiological cost and efficiency of activity are discussed, as well as possibilities of using methods of applied mathematics (correlation and cluster analysis, artificial neural network technology) to describe system organization of physiological functions in healthy people. The question of the use of the proposed regulations to describe the system organization of physiological functions in patients with Parkinson's disease and epilepsy is considered.

Age and Sex Characteristics of the Blood Cytokine Profile in Rats Subjected to Prenatal Stress.

Parameters of blood cytokine profile in male and female rats subjected to prenatal stress on the model of swimming in cold water (10°C, 5 min, days 10-16 of gestation) were studied. Prenatal stress had no significant effects on the blood levels of IL-6 and IL-10 cytokines. The blood concentration of proinflammatory cytokine TNFα in 60-day-old rats was higher than in age-matched controls. Stress led to a lower level of anti-inflammatory IL-4 in the blood of 30-day-old males compared to controls. In female rats subjected to prenatal stress, the concentration of IL-4 decreased on day 21, but increased by day 60 of postnatal ontogeny. Specific effects of prenatal stress on the blood cytokine profile in male and female animals at different periods of ontogeny were revealed. Different and even opposite changes in blood cytokine levels could be largely mediated by sex- and age-specific features of immune functions after prenatal stress.

Effect of Repeated Stress Exposures on the Blood Cytokine Profile in Rats with Different Behavioral Parameters.

Changes in the blood cytokine profile were studied in rats with different behavioral patterns in the open-field test during chronic stress on the model of daily 4-h immobilization over 8 days. The level of proinflammatory cytokines IL-1α and IFNγ in behaviorally active and passive animals changed insignificantly under these experimental conditions. Repeated stress exposures were accompanied by a progressive decrease in the plasma level of IL-2 and IL-5 in passive rats; these changes were most pronounced on day 8 of the study. Active animals were characterized by a tendency toward reduction of IL-2 content, but significant decrease in IL-5 concentration on days 3 and 8 of restraint stress. Blood levels of IL-1ß and IL-6 in rats remained practically unchanged after single immobilization, but progressively increased during further stress exposures and reached maximum on day 8 of stress. The content of the anti-inflammatory cytokine IL-4 in rats was constant, but blood concentration of IL-10 increased during repeated stress exposures. These changes were most pronounced on day 8 in passive animals and on days 3 and 8 of restraint stress in active animals. These data indicate that the direction of variations in the blood cytokine profile of rats under conditions of chronic stress depends on the baseline parameters of behavior and frequency of stress exposures.

Influence of Rhythmically Organized Optical Stimulation on the Performance of Human Cognitive Activity and Spatial Characteristics of the EEG Alpha Range.

We studied the effect of optical stimulation with a frequency of 10 Hz on the cognitive task effectiveness (the "n-back" test) and spatial characteristics based on the coefficients of coherence (Coh) of the general, high, and low ranges of the EEG alpha rhythm in healthy subjects (38 men aged 18-26 years). Based on the performance of the test presented in the optical stimulation absence, groups with high (group 1) and low (group 2) results have been identified. It was found that the optical stimulation led to a decrease in the test effectiveness in group 1 subjects and to an increase in group 2 persons. Optical stimulation increased interhemispheric integration of neural ensembles in a number of cortical areas at frequencies of a high subrange of the alpha rhythm. An increase in interhemispheric cooperation was more characteristic of subjects who increased the test activity effectiveness against the optical stimulation background. It is assumed that the growth of interhemispheric integration caused by rhythmically organized 10-Hz optical stimulation is a factor contributing to an increase in the effectiveness of performing cognitive tasks of this kind.

Changes in the Level of Methylation of a Group of microRNA Genes as a Factor in the Development and Progression of Non-Small Cell Lung Cancer.

We studied changes in the level of methylation of a number of microRNA genes hypermethylated in non-small cell lung cancer and its histological subtypes as well as the relationship of methylation of a group of microRNA genes with clinical and morphological features of the tumor with smoking status. A significantly high level of methylation of 7 genes (MIR124-1/3, MIR125B-1, MIR129-2, MIR137, MIR1258, and MIR339) was revealed in adenocarcinoma and squamous cell lung cancer in comparison with samples of adjacent histologically unchanged lung tissue. In squamous cell lung cancer, a significantly high level of methylation of the MIR124-2 gene in the tumor was also shown. In addition, differences in the methylation profile of adenocarcinoma and squamous cell carcinoma at stages III-IV of the oncological process were revealed. A high level of methylation of the MIR137 and MIR1258 genes was shown for adenocarcinoma and MIR339, MIR129-2, and MIR124-2 for squamous cell carcinoma. Significant differences in the level of methylation of MIR124-2 and MIR375 genes were revealed for smoking patients with squamous cell lung cancer.

Analysis of Endogenous Spectral Power of EEG Alpha-Range Biopotentials during Mnestic Activity under Conditions of Rhythmically Organized Optical Stimulation.

We studied the effect of optical stimulation (10 Hz) on the effectiveness of mnestic activity in the n-back task in healthy subjects (n=32). EEG was recorded at all stages of the examination. The absolute values of the spectral power of the 10 Hz frequency (µV2) of the alpha range were calculated. According to the results of the test without optical stimulation, the examinees were divided into groups with high (group 1) and low (group 2) task performance. In the initial state, the spectral power of 10 Hz was significantly higher in group 1 subjects. Under conditions of screen flickering, the results became poorer in group 1 and better in group 2 in comparison with the results under normal conditions. These changes were accompanied by an increase in the spectral power of 10 Hz only in group 2 subjects. These findings can provide the basis for the development of practical recommendations for improving the mnestic functions in patients with consideration for the individual characteristics of their initial EEG.

Correlation of Physiological Parameters in Rats after Stress Exposure under Conditions of Antigenic Stimulation with Lipopolysaccharide Administration.

We studied correlation dependences between physiological parameters in rats in 3 h, 1 day, and 8 days after administration of LPS (100 µg/kg) at the end of 24-h immobilization stress. In 3 h after LPS administration against the background of stress exposure, significant correlations of metabolic parameters with the relative weight of the adrenal glands and the perceptual component of nociception in rats were revealed. A direct relationship between the concentration of the proinflammatory cytokine TNFα and anti-inflammatory IL-4 was also found in these animals. On the first day after LPS injection, correlations were revealed, predominantly positive, only between the indicators of the cytokine blood profile. In the late post-stress period after antigenic exposure, no correlations between the studied physiological parameters were found. It can be hypothesized that immune modulation through systemic administration of LPS prevents persistent excessive stress of physiological functions at the later stages after stress exposure.

Lymphocyte Index of Peripheral Blood in Rats at Different Stages of the Post-Stress Period under Conditions of Antigenic Exposure and Injection of Lipopolysaccharide.

Changes in the Shaganin lymphocyte index (ratio of the number of lymphocytes to segmented neutrophils) in the peripheral blood of rats after intraperitoneal administration of LPS (100 µg/kg) at the end of a single stress exposure in a model of 24-h restraint stress were studied. The lymphocyte index was analyzed 3 h later, on the 1st and 8th days after the stress load. Immobilization was accompanied by a decrease in this parameter 3 h after exposure. One day after the stress load, an increase in the lymphocyte index was noted, which remained on the 8th day of observation. LPS injection did not affect the changes in this parameter caused by 24-h immobilization on the 1st and 8th days of the study, but prevented a pronounced increase in the lymphocyte index on the 1st day after the stress load. The data obtained expand the existing scientific understanding of the specificity of the involvement of immunomodulatory substances in the implementation of adaptive-compensatory processes in mammals under conditions of emotional stress.

Blood Cytokine Concentration in Rats during Antigenic Treatment after a Single Long-Term Stress Exposure.

We studied changes in the blood cytokine profile of rats 3 h, 1 day, and 8 days after acute stress on the model of 24-h immobilization followed by LPS administration (100 µg/kg intraperitoneally). The concentration of proinflammatory cytokines (particularly of IL-1ß and TNFα) significantly decreased at the early stage after stress exposure and physiological saline injection, but increased in the follow-up period and practically did not differ or even surpassed the control level by the end of observations. Under these conditions, the blood content of anti-inflammatory cytokine IL-10 increased most significantly on day 1 of the post-stress period. Restraint stress followed by LPS administration was accompanied by a decrease in the level of proinflammatory cytokines at the early (IFNγ and TNFα) and late stages (IL-1ß) of the experiment. Directed modulation of the immune status in animals after acute stress was followed by a significant increase in the content of IL-10 on days 1 and 8, as well as by a tendency toward elevation of IL-4 concentration by the end of the study. The directionality and degree of changes in the cytokine profile of mammalian tissues depend on the type of extreme exposure, duration of the post-stress period, and specific effects of exogenous pathogenic factors in the whole body.

Correlation-and-Spectral Analysis of Time Series for Microcirculatory Parameters in Vessels of Symmetrical Organs.

The correlation relationships between microcirculatory parameters were studied in vessels of symmetrical organs in humans. Parameters of microcirculation in healthy volunteers were measured by the method of laser Doppler flowmetry (LDF). LDF-signal transducers were placed symmetrically on the lower parts of the right and left shoulders (3 cm above the elbow bend). Correlations between various components of the amplitude-frequency spectrum for blood flow fluctuations (myogenic, neurogenic, respiratory, and cardiac) were evaluated on symmetrical sides. A significant correlation was found for the mean value of vascular perfusion on the right side with the neurogenic, myogenic, respiratory, and cardiac components on the same side. However, the mean value of vascular perfusion on the light side was interrelated only with the cardiac component. A positive correlation was revealed between the neurogenic and myogenic components on the left side. However, the neurogenic component on the right side was positively related to the myogenic component on the opposite side. Asymmetry of correlation relationships was also observed for the respiratory and cardiac components of study spectrum. Our results illustrate the specific regulation of microcirculatory blood flow in paired organs, which is associated with the existence of functional asymmetry. The physiological mechanisms for this asymmetry require further experimental and clinical studies.

Correlation Connections between Individual-and-Typological Features, Indices of Performance of Goal-Directed Activity, and Heart Rate Variability Parameters.

Correlation analysis of the performance of goal-directed activity and heart rate variability parameters in people with different individually-typological features was conducted on the model of endosurgical training. It was found that people with low level of intro-extroversion and neuroticism, but high index of situational anxiety were more successful during goal-directed behavior. The subjects with low level of neuroticism finished the tasks more quickly, both at the beginning and at the end of the observations. It was established that the number of mistakes in subjects with low personal anxiety on the 10th day of training was lower than in high-anxious individuals. It is shown that people with high rate of intro-extroversion are characterized by more pronounced increase in parasympathetic influences during basic endosurgical training. Hence, the achievement of the result in extroverts in these experimental conditions is provided by lower physiological penalty than in introverts. The definition of psychophysiological indices could be recommended for inclusion in the complex of measures for the assessment of proficiency in the training of endosurgeons.

Neurological Deficit and Structural Changes in Lymphoid Structures of the Tracheal Wall in the Immediate Stage of Experimental Hemorrhagic Stroke in Rats with Different Behavioral Activity.

Specific features of neurological deficit and changes in the cellular composition of tracheal lymphoid structures during the immediate stage (day 1) of hemorrhagic stroke were studied in rats with various behavioral parameters. Modeling of hemorrhage in the left caudate nucleus of the brain was followed by the development of motor disturbances in the forelimb use asymmetry test and corner rotation paradigm. These animals preferred to use the left forelimb (ipsilateral to the side of hemorrhage) to lean on the cylinder wall. The frequency of using the right forelimb or both forelimbs was reduced under these conditions. The number of left-sided rotations increased, while the percentage of right-sided rotations decreased. The observed changes were accompanied by immune dysfunction. It was manifested in the depletion of lymphoid aggregates of the tracheal wall in lymphocytes and plasma cells. The severity of abnormal neurological symptoms and disturbances in immune homeostasis during the immediate stage of hemorrhagic stroke was greater in behaviorally passive rats than in active specimens.

Blood Cytokine Profile in Rats with Different Behavioral Characteristics after Metabolic Stress.

Changes in the blood cytokine profile in rats with various parameters of behavior were studied under conditions of 5-day starvation not followed by the recovery period or with subsequent normalization of food intake. Metabolic stress had no effect on the content of most cytokines. The concentration of pro- and anti-inflammatory cytokines in blood plasma of rats was shown to increase significantly by the end of a 5-day recovery period after food deprivation. These changes in behaviorally passive specimens were more pronounced than in active animals. Therefore, differences in the strain of immune reactions in mammals with different prognostic resistance to extreme factors are most pronounced during the post-stress period. These data illustrate the necessity of an individual approach to studying the systemic organization of physiological functions under normal and pathological conditions.

State of Stress-Marker Organs in Rats after a Single Exposure to Long-Term Stress and Treatment with Lipopolysaccharide.

We studied the effect of LPS on the state of stress-marker organs in rats at various periods after a single exposure to long-term stress on the model of 24-h immobilization. The animals were intraperitoneally injected with LPS in a dose of 100 µg/kg immediately after the negative emotiogenic exposure. Changes in physiological parameters were evaluated 3 h, 1 day, and 8 days after immune stimulation. Acute stress was accompanied by a decrease in the weight of the thymus during all stages of the post-stress period. An increase in the relative weight of theadrenal glands in animals under these conditions was observed only on day 8 after restraint stress. The induction of immune reactions due to systemic treatment with LPS was shown to prevent involution of the spleen in the late stage after a single exposure to long-term stress (day 8). Hypertrophy of the adrenal glands, which serves as one of the typical reactions of mammals to negative emotiogenic factors, was not revealed during the post-stress period after antigenic stimulation. These data hold much promise for the development of new approaches to the use of immunoactive substances to prevent or reduce the severity of physiological changes after emotiogenic loads.

Cellular Composition of the B- and T-Cell-Dependent Areas in the Small Intestine during the Post-Stress Period (Experimental Study).

A quantitative study of lymphoid cells in the B- and T-cell-dependent areas of intestinal lymphoid nodules and mesenteric lymph nodes in behaviorally passive and active rats was performed at various periods after acute stress on the model of 1-h immobilization with simultaneous electrocutaneous stimulation. Stress exposure is accompanied by a decrease in the number of lymphoid cells in immunogenic structures of the gastrointestinal tract. Post-stress changes in the cytoarchitectonics of B- and T-cell-dependent areas in mesenteric lymph nodes of animals are less pronounced than in lymphoid nodules. Quantitative changes in lymphoid cells of B-cell-dependent areas in the small intestine of rats are greater than in T-cell-dependent areas. Changes in the cellular composition of immunogenic structures in the digestive system are most significant at the early stages of the post-stress period (1st week). Passive rats are characterized by significant changes in the cytoarchitectonics of B- and Tcell-dependent areas in the small intestine after extreme exposure, which illustrates functional exhaustion of the lymphoid tissue in stress-predisposed specimens.

Blood Cytokine Profile in Rats with Various Behavioral Characteristics after a Single Exposure to Long-Term Stress.

Changes in the blood cytokine profile of rats with different behavioral activity were evaluated in various periods after stress exposure on the model of 24-h immobilization. Behaviorally active animals exhibited only a tendency to a change in the concentration of study cytokines in the dynamics after experimental stress. Stress exposure in passive specimens was accompanied by a decrease in the content of pro- and anti-inflammatory cytokines. These changes were most pronounced at the early stages of the post-stress period and persisted until the end of observations. After a single exposure to long-term immobilization, cytokine level in the peripheral blood of behaviorally passive animals was much lower than in active rats. Variations in immune indexes of mammals depend on the initial parameters of their behavior and duration of the post-stress period. Differences in the blood cytokine profile during negative emotiogenic exposures in passive and active rats are probably related to the specifics of immune reactivity in specimens with various sensitivities to stress.