Long-Term Effect of Moderate Hypoxia and Chronic Administration of Fluoxetine during the Neonatal Period on Cognitive and Stress-Hormonal Functions in Adult Male Rats.

We studied the effect of moderate neonatal normobaric hypoxia on the indicators of spatial learning, memory, and reactivity of the hypothalamic-pituitary-adrenocortical system in adult male Wistar rats. The pharmacological effect of chronic injections of the serotonin reuptake inhibitor fluoxetine during the neonatal period on the studied behavioral and the physiological indices was evaluated. Hypoxia impaired spatial training, increased the short-term memory performance, but did not change long-term memory and stress indicator in response to its testing. The use of fluoxetine normalized learning, but did not change memory indicators and the stress-induced level of corticosterone in blood plasma in the hypoxic rats and control animals. New results indicate a protective effect of fluoxetine in the neonatal period under conditions of moderate normobaric hypoxia.

Sexual Dimorphism in the Effect of Neonatal Inflammatory Pain on Stress Reactivity of Hormonal Response and Cognitive Functions in Adult Rats.

The effect of moderate neonatal stress induced by inflammatory pain in rat pups of both sexes on the hormonal response and cognitive processes in adult animals was studied in the Morris water maze. No significant differences in spatial learning and memory were found in experimental rats exposed to neonatal inflammatory pain vs. control animals. However, experimental rats exhibited sex differences in long-term spatial memory whose efficiency was higher in males vs. females. After long-term memory testing, stress responsiveness of the hypothalamic-pituitary-adrenocortical axis, as assessed by the plasma corticosterone level in the formalin test, was higher in experimental males vs. females. Only experimental females exhibited differences between short-term and long-term memory, with the efficiency being higher in the former. Thus, sexual dimorphism was found in the effect of neonatal nociceptive stress on long-term spatial memory in adult rats: experimental males vs. females demonstrated more effective long-term memory combined with a higher stress reactivity of the hormonal response.

Dependence of Brain-Computer Interface Control Training on Personality Traits.

Personality traits (PTs) are predictors of the success of control of brain-computer interfaces (BCIs); however, it is unknown how the PTs that are optimal for BCI control changes during training. The paper for the first time analyzes the correlations between PTs and the accuracy of the classification (AC) of brain states in imagining the movements of the hands, feet, and locomotion during 10-day training of ten volunteers in BCI control. In the first 3 days of training, the AC is higher for more stressed and anxious volunteers; in the last days, for calmer ones. In the middle of the training period, AC is higher in low-demonstrativeness persons, it is more pronounced when imagining foot movements. Correlations of low demonstrativeness, as well as of foresight and self-control with AC when imagining foot movements are revealed significantly more often than when imagining hand movements and locomotions. During almost the entire period of training, AC with locomotion imagination is higher in individualists. The results make it possible to propose individually-oriented recommendations for the use of BCI based on the imagination of movements for the rehabilitation of patients with motor disorders.

A New Technology for Recovery of Locomotion in Patients after a Stroke.

Neural networks in the spinal cord can generate the walking pattern and control posture in the absence of supraspinal influences. A technology using transcutaneous electrical spinal cord stimulation (tSCS) was created. During walking, tSCS activated spinal locomotor networks, as well as leg flexor/extensor motor pools in the swing/stance phases, respectively. It was assumed that the use of this technology in subjects with locomotion disorders would improve walking. Patients with hemiparesis were studied 3-11 months after stroke, the duration of the course was 2 weeks. Patients of the main and control groups received standard therapy and rehabilitation using the technology; in the control group, sham tSCS was used. After the course, minimal clinically important differences in walking parameters were achieved in the main group, in contrast to the control group. The developed technology is an effective means of restoring walking in patients with hemiparesis.

Interhemispheric Asymmetry and Personality Traits of Brain-Computer Interface Users in Hand Movement Imagination.

Personality traits of users can affect the success in controlling brain-computer interfaces (BCIs), and the activity of right and left brain structures may differ depending on personality traits. Earlier, it was not known, how the success of BCI control with different personality traits is associated with interhemispheric asymmetry. In this work, the dependence of the success of imagination of movements, estimated by the success of recognition of EEG signals during imagination of hand movements compared to rest state, on the user's personal characteristics was studied. It is shown that in single control of BCI by naive subjects, recognition success in imagining right-hand (RH) movements was higher in expressive sensitive extroverts, and in imagining left-hand movements (LH) it was higher in practical, reserved, skeptical, and not very sociable persons. It is suggested that this phenomenon may be based on interhemispheric differences in dopamine level and in the way of encoding movement information.

[On the use of mathematical statistics methods in clinical and experimental studies.]

In the paper a number of issues, including conceptual ones, related to the specific features of making statistical decisions, choosing tests and computing characteristics that will strengthen the evidence base of the conclusions obtained when analyzing data using methods of mathematical statistics, are considered. The paper aims not to describe the methods of mathematical statistics themselves, but to analyze the conditions and the need to apply the most common tests. In particular, the magnitude of the indicator of the statistical significance of the observed effects - p-value - and the sample size to obtain a significant effect are discussed, the effect of multiple comparisons, the application of the Bayesian approach, and others are considered.

Soluble Guanylate Cyclase As the Key Enzyme in the Modulating Effect of NO on Metabotropic Glutamate Receptors.

The synaptic plasticity of the afferent synapse of the vestibular apparatus is defined by the dynamic interaction of ionotropic and metabotropic glutamate receptors and the modulators of synaptic transmission. It was shown that nitric oxide modulates iGluR responses. In this paper, the effect of NO on the function of the afferent synapse mGluR was investigated. Inhibitor of nitric oxide synthase lowered the level of background activity but increased the amplitude of the responses of groups I and II mGluR agonist ACPD. Donor NO SNAP increased the level of background activity. Short-term perfusion of the synaptic region with low concentrations of SNAP led to a decrease in the amplitude of the answers of mGluR agonists ACPD and DHPG. The inhibitory effect of the NO donor was eliminated under blockade of soluble guanylate cyclase with a specific inhibitor ODQ. A prolonged application of NO did not cause a statistically significant change in the amplitude of the ACPD response. However, SNAP at concentrations of 10 and 100 µM increased the amplitude of the mGluR agonist responses 30 and 15 minutes, respectively, after termination of the NO donor exposure. The obtained data show the multidirectional effect of NO on the function of mGluR and testify to the existence of a complex modulating mechanism of the afferent flow from vestibular organs to the central nervous system.

[INVOLVEMENT OF 5-HT1A RECEPTORS IN LONG-TERM INFLUENCE OF INFLAMMATORY PAIN AND STRESS IN EARLY AGE ON REACTIVITY OF NOCICEPTIVE SYSTEM].

Effects of inflammatory pain, short stress of maternal isolation and combination of these impacts in 1-day-old and repeatedly 2-day-old rat pups (neonatal period of development) on the indices of generalized pain and the inflammatory pain response were studied on the rats during the adulthood. To study the involvement of 5-HT1A receptors in the long-term impact of neonatal effects on pain sensitivity we used a chronic injection of 5-HT1A receptor agonist buspirone during the prepuberal period of rats which as newborn experienced similar impacts (control, injection of saline). It was found that in adult rats in which inflammatory pain and stress of maternal isolation during the first two days of life caused changes in pain sensitivity, buspirone normalized the indices of basic pain in the hot plate test and the pain response in the formalin test; the combination of these impacts did not cause any changes in the pain sensitivity, and the effect of buspirone did not appear. Thus, effects of buspirone found in this study suggest that 5-HT1A receptors are involved in the long-term influence of the studied adverse neonatal impacts on the reactivity of the nociceptive system.

[Latency of Evoked Potentials in the Tasks Involving Classification of Images after Wavelet Filtration.]

We studied the characteristics of evoked potentials recorded during the recognition test based on four types of series of images subjected to the wavelet filtration: images of living objects containing either low frequency or high frequency portion of the spatial frequency spectrum, and imaging of non-living objects in the same two spatial frequency bands. Each subject had to classify the image either by its semantic feature (live-not live), or by its physical feature (low-high frequency). The purpose of this study was to compare the time characteristics of evoked potentials in these two types of tasks, which provides information on the time characteristics of categorization mechanisms of visual images. Analysis of the latent periods and amplitudes of the components of evoked potentials enabled to detect the occipital areas of the leads where the early components (up to 170 ms) are associated with spatial and frequency characteristics of the image, the frontal and temporal areas where the components of 170-200 ms correspond with the process of categorization, and the later frontal, central and parietal areas (300-500 ms) correspond with the process of error detection and the organization of motor response.

[DIFFERENCES IN ADAPTIVE BEHAVIORS IN ADOLESCENT MALE AND FEMALE RATS EXPOSED AS NEWBORNS TO INFLAMMATORY PAIN OR STRESS].

In adolescent rats (25-35-day-old) exposed as newborns (the first and repeatedly second days) to adverse impacts (inflammatory pain, stress of short-term maternal separation or their combination) sex dimorphism was revealed in pain behavior under conditions of similar peripheral inflammation. According to the priority data obtained, strengthening of pain-related response in the formalin test was found in males, whereas pain sensitivity in females was not changed, that is pain experienced by them as newborns did not affect the system reactivity to the same chemical irritant in the adolescent period. However, the rats of both sexes, who experienced short-term stress of maternal deprivation (60 min-during the first and the second days of life), displayed increased pain sensitivity in the formalin test. Combined effect of inflammatory pain and maternal deprivation in newborns did not alter pain sensitivity in both adolescent males and adolescent females. The male and female rats exposed as newborns to maternal deprivation displayed a decrease of the anxiety level in the elevated plus maze; the rats, exposed to each of the above-mentioned early impacts showed a decline of adaptive behavior in the forced swimming test; the males exposed to pain and combined impacts demonstrated impairment of spatial learning in Morris labyrinth. Thus, we pioneered in demonstrating sex differences in the effects of inflammatory pain in newborn pups on pain sensitivity in the formalin test in adolescent rats. Separation of the influence of early stress or pain was revealed in adolescent females in the formalin test: maternal deprivation induced hyperalgesia, whereas pain failed to change functional activity of the tonic nociceptive system.

[ROLES OF CONSTITUTIVE SYNTHASES OF NITRIC OXIDE IN THE REGULATION OF GASTRIC BICARBONATE SECRETION INDUCED BY MILD IRRITATION OF THE MUCOSA].

Roles of isoforms of constitutive synthase of nitric oxide, neuronal or endothelial (nNOS or eNOS), in control of gastric bicarbonate secretion induced by mild irritation of the gastric mucosa was assessed at the normoacid state or after blockade of gastric acid secretion with omeprazole. In anesthetized rats, the concentration of HCO3- in luminal perfusate was calculated basing on measurements of pH/PCO2. Mucosal irritation during 20 min with acidic hypertonic solution (1 M NaCl, pH 2.0) caused marked and omeprazole-independent increase of HCO-secretion. Selective blocker ofnNOS in vivo 7-nitroindazole (7-NI), and the nonselective blocker ofnNOS and eNOS, N(G)-nitro-L-arginine (L-NNA), were applied either intravenously (10 mg/kg), or locally via retrograde injection into the splenic artery (1 mg/kg). At the normo-acid state, the irritation-induced secretion of was suppressed by 7-NI, but was not affected by L-NNA. After administration of omeprazole, both 7-NI and L-NNA equally inhibited HCO3- output. The effect of 7-NI (but not L-NNA) was abolished by cyclooxygenase (COX) inhibitor, indomethacin, which by itself suppressed irritation-induced secretion of HCO3-. Additionally, bicarbonate output was substantially reduced by the blocker of soluble guanylate cyclase (GC), methylene blue. We conclude that irritation-induced secretion of HCO3- is largely mediated by intramural nNOS and depends on GC-COX interaction. As it was theoretically estimated, eNOS activity caused a reduction of HCO3- output in the normo-acid stomach. Omeprazole abolished the effect of eNOS.

[The Spatial-Frequency Characteristics of the Visual System in Schizophrenia].

In order to determine the spatial-frequancy characteristics of the visual system of healthy subjects and patients with schizophrenia, we used the contrast comparison of two Gabor gratings with sinusoidal distribution of brightness. The Gabor gratings have low, medium or high spatial frequencies; the neurons of magnocellular and parvocellular channels are sensitive to these frequencies to different extents. We found an increase in sensitivity to the contrast when comparing the gratings with low frequencies (to which magnocellular channels are most sensitive) in the patients with first-episode schizophrenia who had not receive long-term antipsychotic treatment, as compared with the control group. On the contrary, the sensitivity to the gratings with medium and high spatial frequencies in this group of patients was lower, as well as in patients with first-episode schizophrenia who had received long-term treatment. The patients with chronic schizophrenia showed a decrease in contrast sensitivity in all tested ranges of frequencies. We obtained supplementary evidence of the enhancement of internal noise in the visual system of the patients with schizophrenia. The results help us to explain the clinical data on the development of visual perceptual diorders at different stages of schizophrenia.

[Long-term changes in adaptive behavior of rats after neonatal inflammatory pain].

In this study we addressed the tonic nociceptive system functional activity in the formalin test, anxiety- and depression-like behaviors and spatial learning in adolescent male rats exposed in the neonatal development to repeated inflammatory pain peripheral stimulation. The following groups of 25-day-old rats were used after being exposed on days 7 and 8 to: 1) formalin-induced inflammatory pain with maternal separation for 60 min (FS), 2) the same inflammatory pain stimulation without maternal separation (FWS), 3) physiological saline injection with maternal separation for 1 h (SS), 4) physiological saline injection without maternal separation (SWS) and 5) no stimulation (intact rats). The data obtained indicate that pain caused in 7-8-day-old rat pups by formalin injection into the plantar pad of the hind paw manifests by adolescence (day 25 as a strengthened inflammatory response under the analogous painful stimulation in the formalin test, adaptive behavior disorder in the forced swimming test and spatial learning disability. Our findings that a short-term repeated maternal deprivation of the 7-8-day-old rat pups without inflammatory pain increases the depression-like behavior are also of particular interest. Thus, a repeated inflammatory pain during the neonatal development brings about significant changes in the adaptive behaviors studied as well as in spatial learning in adolescent rats.

[Specific characteristics of mismatch negativity in infants].

The mismatch negativity component of auditory event-related potentials was studied in fulI-term infants of the first month of life and adults. Acoustic stimuli with large deviance in passive oddball task were used. Research data revealed distinctive features in morphology and specificity in parameters of positive mismatch component in children at early ages. Contrary to results from adult group infant component was manifested in two positive peaks, greater amplitude and longer latency. A significant positive correlation was observed between infant's conceptual age and amplitude, and significant negative correlation was found between gestation age and latency for this positive component. Results allowed proposing specificity in parameters of infant's positive mismatch component indicated proceeding maturational changes in auditory cortex at early ages.

[Long-term effects of stress in critical periods of development on reactivity of adult female rats].

Effects of stress during different periods of ontogeny, namely, the prenatal, prepubertal, or their combination (prenatal+prepubertal), on the indices of psychoemotional and tonic pain-related behaviors, as well as corticosterone reactivity after pain behavior were investigated in adult 90-day-old female Wistar rats. Our data show for the first time, the similarity of effects of prenatal (immobilization stress of a rat dam during the last week of pregnancy) and prepubertal (forced swimming, pain-related response in the formalin test) stresses on the indices under study, an increase in the time of immobility and in licking duration, but the difference between effects of combined stress on these indices. Pain-related response increased corticosterone in prepubertally stressed rats while in prenatally stressed rats, decreased it. In rats experienced combined stress, formalin-induced pain increased corticosterone as compared with that in prenatally, but not in prepubertally stressed rats. A positive correlation between pain-related reaction and stressed hormonal response was revealed in prepubertally stressed animals. So, long-term effects of stress during critical periods of ontogeny determine stress reactivity of behavioral and hormonal responses in adult female rats.

[Effects of prenatal influences of buspirone and stress on indices of inflammatory pain response and depressive behaviour in adult rats].

New data on complex realization of anxiolytic, antidepressive and antinociceptive effects of prenatal injections of a 5-HT1A agonist buspirone were obtained in prenatally stressed adult rats. Buspirone was injected to female rats from the 9th to 21st days of pregnancy; during the last week of pregnancy buspirone was injected 10 min before immobilization stress. In the adult offspring of both sexes, behavioral indices of tonic pain response in the formalin test and the indices of depression in the forced swim test were investigated. The choice of the target was defined in accordance with available literature data on the role of 5-HT1A receptors in the mechanisms of prenatal stress, of formation of the ascending link of the nociceptive system, of development of depression, and in the mechanisms of the treatment ofnociceptive information. Prenatal stress increased the duration of licking and the time of immobility, the indices of tonic pain and depression in the rats of both sexes. Buspirone evoked the decrease of the indices investigated in prenatally stressed rats in both tests in comparison with the relevant indices in prenatally stressed rats that were not subjected to buspirone. Thereby, it has been demonstrated that buspirone normalized the indices of the tonic pain response modified by prenatal stress; a considerable decrease of the index of depression suggests that there are differences in mechanisms of antinociceptive and antidepressive effects of buspirone. The data on complex realization of anxiolytic, antidepressive and antinociceptive effects ofbuspirone stimulate the attention of clinicians and prompt further investigations in this direction.

[Selective influence of dehydroepiandrosterone-sulphate on anxiety induced by corticotropin-releasing hormone injection].

The objective of this study was to ascertain the effect of dehydroepiandrosterone-sulphate (DHEA-S) on changes of anxiety level, induced by corticotropin-releasing hormone (CRH) injection. Active and passive rats were selected from Wistar rats on the basis of T-maze testing. Active rats were then divided into the groups with high (HA) and low anxiety (LA) level after testing in elevated-plus maze. Intranasal injection of CRH induced increase of anxiety level in the LA rats, while in HA rats it remained unchanged. DHEA-S exerted a moderate anxiolytic effect on the LA rats and sedative effect--on the HA rats. DHEA-S injection had no effect on anxiety level in passive rats that typically demonstrate high level of trait-anxiety and resistance to CRH. These results suggest that DHEA-S effect depends on the individual psycho-emotional status and responsiveness to CRH.

Interrelationship between measures of pain reactions in inflammation and levels of depression in prenatally stressed rat pups.

The interrelationship between measures of pain reactions (number of flexion + shaking patterns) in the formalin test and the level of depression (duration of immobility) in the forced swimming (Porsolt) test was studied in prenatally stressed rat pups aged 7-8 days. Two series of experiments were performed, with different sequences of tests separated by intervals of one day. In the first series of experiments, the Porsolt test was performed first; in the second series, the formalin test was performed before forced swimming. The sequence of tests was found to have different effects on measures of pain and depression and their correlation in prenatally stressed and unstressed rat pups. The effects of the sequence of the depression test (before or after the formalin test) on measures of depression were different in prenatally unstressed and stressed rat pups. In the former there were no differences between the two test sequences, while in prenatally stressed rat pups the first sequence showed a significant increase in the duration of immobility. The order of testing had no effect on the pain response--there were no differences between the numbers of flexion + shaking patterns in either prenatally stressed rat pups or unstressed animals; measures of the pain response were significantly greater in the sequence in which the formalin test was followed by the Porsolt test in prenatally stressed individuals as compared with unstressed animals. A positive correlation between study parameters was seen in the first series in prenatally unstressed rat pups, while there was a negative correlation in prenatally stressed animals. In the second series, there were no significant relationships between measures. Thus, the sequelae of postnatal stress, as imposed by each test the day before the final test, were apparent only in prenatally stressed animals in terms of the level of depression.

[Infants stage of rat development in behavioral parameters of depression-like state and pain response].

In the 7-8- and the 10-11-day old male rat pups born to dams exposed to an immobilization stress for the last week of pregnancy and to the dams exposed to no stress (control), behavioral parameters were studied: the level of depression in the test of forced swimming (the Porsolt's test) and 24 h after a long pain response during inflammation (the formalin test--a subcutaneous injection of 2.5% formalin into the hind leg plantar pad). In control pups, significant age-related changes in the forced swimming were revealed: the immobility time was longer in animals of the older age group, whereas no age differences were found in parameters of the persistent inflammatory pain and in flexing + shaking behavior. The prenatal stress produced an increase in the immobility time and the flexing + shaking behavior in the 7-8-day old, but not in the 10-11-day old pups. This resulted in elimination of the age differences in the immobility time in the prenatally stressed animals. Thus, use if different methodic approaches has allowed peculiarities in the parameters of the degree of depression and duration of the pain response at inflammation in the 7-8- and 10-11-day old rat pups, which indicates heterogeneity of the infant development stage that, according to literature data, includes in rats the period from the 5th to the 10th postnatal days.

A simple method for measuring brain asymmetry in children: application to autism.

A device for measuring signal transfer within and between hemispheres has been developed at the Center for Neuropsychological Research at the University of Trier, Germany. It contains two identical panels allowing both tactile stimulation and motor response with buttons for the fingers of each hand. The buttons have two functions. They can exert a slight tactile stimulation to a finger, and they can be pressed down by the finger to provide a motor response to the tactile stimulation allowing measuring the response time. The device was used for measuring brain asymmetry in tactile processing autistic children. The participants were given a finger tapping test followed by the procedures with unilateral and bilateral processing of tactile stimulation. All participants responded positively to the test procedure and accepted it as a kind of game. The results indicated that brains were more asymmetrical in autistic children than in controls: The right hemisphere functioned quicker than the left hemisphere.