[FREQUENCY-TEMPORAL STRUCTURE OF HUMAN ELECTROENCEPHALOGRAM IN THE CONDITION OF ARTIFICIAL HYPOGRAVITY: DRY IMMERSION MODEL].

Frequency-temporal electroencephalogram (EEG) reactions to hypogravity were studied in 7 male subjects at the age of 20 to 27 years. The experiment was conducted using dry immersion (DI) as the best known method of simulating the space microgravity effects on the Earth. This hypogravity model reproduces hypokinesia, i.e. the weight-bearing and mechanic load removal, which is typical of microgravity. EEG was recorded by Neuroscan-2 (Compumedics) before the experiment (baseline data) and at the end of day 2 in DI. Comparative analysis of the EEG frequency-temporal structure was performed with the use of 2 techniques: Fourier transform and modified wavelet analysis. The Fourier transform elicited that after 2 days in DI the main shifts occurring to the EEG spectral composition are a decline in the alpha power and a slight though reliable growth of theta power. Similar frequency shifts were detected in the same records analyzed using the wavelet transform. According to wavelet analysis, during DI shifts in EEG frequency spectrum are accompanied by frequency desorganization of the EEG dominant rhythm and gross impairment of total stability of the electrical activity with time. Wavelet transform provides an opportunity to quantify changes in the frequency-temporal structure of the electrical activity of the brain. Quantitative evidence of frequency desorganization and temporal instability of EEG wavelet spectrograms may be the key to the understanding of mechanisms that drive functional disorders in the brain cortex in the conditions of hypogravity.

[Experimental approaches to investigation into the role of the genotype by the locus TAG 1A of dopamine D2-receptors in epileptogenesis].

The effect of genotype in locus TAG 1A of gene receptor dopamine second type on characteristics of peak-and-wave EEG pattern in somatosensory, parietal and occipital areas of the cortex was studied in two groups of rats. Quantitative analysis showed that the peak-wave discharge of the first type in rats with A1/A1 genotype had a significantly longer duration, occurred more frequently leading to a significant increase in their peak-wave index. The results are of clinical interest creating a theoretical basis for improved diagnosis of absence epilepsy and selection of anticonvulsants.

[Premature aging of an organism and characteristics of its manifestation in remote period after low dose irradiation].

In this study 58 participants of the liquidation of the consequences of Chernobyl accident in 1986-1987 were investigated. All the patients complain of constant headaches, disorders of memory, general weakness, rapid fatigability, decreased sexual drive, emotional instability etc. The complex (comprehensive) modern methods of investigation were used to carry out the objective assessment of presented complains and of character of the central nervous system damage: complex computer quantitative analysis of mental capacity; analysis of personality traits by using the MMPI test; single photon emission tomography (with the drug of Ceretec); X-ray computer tomography; magnetic resonance computer tomography. The experimental study with examination of primates who were exposured in sum dose 1 Gy (by drop method) was carried out, too. The results of complex investigation of participants of liquidation of Chernobyl accident consequences enable to postulate the formation of premature aging of an organism in these persons. Data of the experimental study of primates irradiated in dose 1 Gy revealed formation of the brain atrophy in the remote period after low dose radiation exposure.

[Temporal sequence of SWD emergence and spontaneous jerks in WAG/Rij rats with absence epilepsy].

In rat model of absence epilepsy, abnormal complex movements of cervicothorathic part (jerks) were observed in the state of passive wakefulness. When a desynchronized low-amplitude electrical activity was recorded in the parietal and visual cortex, either SWD or jerks were observed. The SWD appearance prevented a jerk. If the discharge appeared between jerks, the interval between jerks increased. Particularly important is the fact that after subtraction of the discharge duration, the distribution of intervals between jerks became the same as in the absence of the SWD. This finding shows that an SWD just interrupts the development of a jerk. That is, when the discharge is over, the jerk develops from the level at which it was stopped by the discharge rather than from the initial level of excitation.

The brain 5HTergic response to an acute sound stress in rats with generalized (absence and audiogenic) epilepsy.

The brain serotoninergic (5HTergic) system of epileptic subjects can influence their vulnerability to stress. We studied the putative dependency of 5HT neurotransmission parameters on emotional stress, and the presence, types and severity of seizures using rats with genetic generalized (absence and/or audiogenic) epilepsy, of WAG/Rij and Wistar strains. The animals were stressed by exposure to a short aversive noise or left without sound stimulation. Tissue concentrations of 5HT, tryptophan (TRT) and 5-hydroxyindolacetic acid (5HIAA) were assessed by HPLC. The stressor activated the 5HTergic system within thalamus (5HIAA elevated), frontal cortex (5HT, TRT elevated), hypothalamus (increased TRT) in all rats. However, the normal (non-epileptic) rats displayed the highest response in the frontal cortex and the lowest one in the thalamus, as compared to the epileptic rats. Absence-epileptic rats exhibited higher thalamic 5HIAA increase than their controls. Significant correlations existed between propensity of absence epilepsy and 5HTergic parameters measured in the cortex and hypothalamus of absence-epileptic rats. No major difference was found between groups with and without audiogenic epilepsy. The results imply that the stress response depends on the presence of epileptic pathology and the seizure type and severity. The brain 5HT may be involved in the control of the paroxysms and behaviour in absence-epileptic subjects.

Audiogenic seizures associated with a cortical spreading depression wave suppress spike-wave discharges in rats.

To study the role of the cortex and sub-cortical structures in the generation of epileptic spike-wave discharges in more detail, cortical and striatal activity was eliminated by the induction of spreading depression in a non-invasive way. EEG and DC potentials were recorded from the cortex and striatum of WAG/Rij rats. Several of these rats show two forms of generalised epilepsy: spontaneously occurring non-convulsive absence seizures, together with convulsive audiogenic seizures. The latter can be evoked by a brief sound stimulation, provoking a fit of wild running, which is regarded as the first phase of an audiogenic seizure. In a majority of fits the cortical DC potential does not show main changes, while the spontaneously occurring spike-wave discharges are briefly suppressed for some minutes. In a minority of fits, however, audiogenic seizures are associated with a spreading depression wave, clearly expressed in the cortical DC potential. This wave is bilaterally initiated in the cortex and propagates to the caudate nucleus of the striatum. In these cases spontaneously occurring spike-wave discharges are fully suppressed for about 1 h. It is suggested that cortical spreading depression, triggered by a short audiogenic seizure, induces a long-lasting suppression of spike-wave discharges. These results are in line with the concept that spike-wave discharges are originally initiated in the cortex, as proposed by the 'cortical focus' theory. The precise role of the striatum remains less clear, although this structure seems not to play a pivotal role in spike-wave generation.

Convulsive and nonconvulsive epilepsy in rats: effects on behavioral response to novelty stress.

Behavioral response to a new environment of Wistar and WAG/Rij rats with absence and/or audiogenic seizures (AGSs) was investigated. Behavior was observed in open-field (OF) and light-dark choice (LD) tests. Correlations of test performance with seizure parameters were evaluated. AGS-susceptible Wistar rats exhibited reduced exploration (rearing) in both tests and a tendency toward hyperlocomotion in the OF test. Genetically absence-epileptic WAG/Rij rats demonstrated agitation (increased vertical/horizontal locomotion, enhanced defecation/urination) in the LD test, whereas they exhibited reduced exploration, increased grooming, and hyperlocomotion in the OF test. Anxiety level, as estimated by grooming time in the OF test and latency to first "risk assessment" in the LD test, correlated positively with the propensity for absence seizures in WAG/Rij rats not susceptible to AGSs. It can be concluded that the behavioral response to novelty stress in epileptic subjects depends on the type and severity of seizures.

The multiple effects of ketamine on electroencephalographic activity and behavior in WAG/Rij rats.

The effects of ketamine, a noncompetitive antagonist at the NMDA receptor, were studied on the EEG and in the open field in a genetic animal model of generalized absence epilepsy--the WAG/Rij rat strain. Animals of this strain display spontaneous occurring generalized spike-wave discharges (SWDs) in the EEG. Ketamine was systemically administered in a dose range from 3 to 30 mg/kg. Biphasic effects of ketamine were observed in the EEG. The first phase was a dose-dependent suppression of SWDs, followed by a second phase characterized by the facilitation of SWDs. This increase was expressed first as an increased number of SWDs, and later on as a significant prolongation of individual discharges and decrease in frequency of SWDs. An obvious amplitude modulation of the discharges was also found. During the period of suppression of SWDs, a new phenomenon was observed: quasi-periodic groups of spikes or wave spikes, with an internal frequency of 4-5 Hz and a periodicity of about 5 s. That quasi-periodic activity vanished a few minutes prior to the recovery of the classical SWDs. However, a specific 5-s amplitude modulation of SWDs remained present in the recovery period. The propensity of that specific ketamine-induced activity was found to be correlated with propensity of SWDs in background EEGs of drug-free animals. Ketamine also produced a dose-related initial behavioral excitation, a decrease of muscle tone in hind quarters, followed by front quarters and head, and an absence of locomotor activity. However, the time course of the behavioral changes cannot explain the effects on the EEG. It can be concluded that ketamine has more effects on the EEG than previously assumed which cannot be explained by a simple blockade of the NMDA receptor. It is proposed that the obtained specific dynamics of SWDs' frequency may be caused by changes in the activity of the thalamo-cortical pacemaker that is generating SWDs.

[The influence of neonatal ketamine injection on pain sensitivity and audiogenic seizures in adult rats]. / Vliianie neonatal'nogo vvedeniia ketamina na bolevuiu chuvstvitel'nost' i audiogennye sudorozhnye pripadki vzroskykh krys.

The remote effects of neonatal (on the 3d-to-9th postnatal days) ketamine injections (10 and 50 mg/kg in 20 microliters of distilled water, s.c.) were analyzed in adult Wistar, WAG/Rij, and KM (a strain with high audiogenic sensitivity) rats. Both ketamine and water injections increased pain sensitivity in adult rats. Neonatally injected water increased the mean score of seizures in Wistar and WAG/Rij, whereas ketamine water solution injected in the dose of 50 mg/kg did not change the seizure intensity (as compared to the intact control). Consequently, ketamine significantly reduced the mean score of the audiogenic seizure fit without change in its latency. In highly sensitive KM rats the neonatally injected ketamine (50 mg/kg) significantly shortened the mean latency of the fit onset, and fit stages developed faster. Thus, the neonatal ketamine injection increased the audiogenic seizure susceptibility of brain structures in KM rats.

[Post-radiation effect on the interhemispheric asymmetry in EEG and thermography characteristics]. / Postradiatsionnye narusheniia mezhpolusharnoi asimmetrii élektroéntsefalograficheskikh i termograficheskikh kharakteristik vo vremia kognitivnoi deiatel'nosti.

Complex analysis of EEG and thermographic parameters carried out in 10 healthy subjects and 34 patients, Chernobyl clean-up participants revealed a correlation between EEG and brain temperature changes in the baseline state and during mental arithmetic. During cognitive activity the maximal increase in the average EEG coherence and temperature shifts in healthy subjects were observed in the left frontotemporal and right parietotemporal areas. In patients changes in both parameters under study were most pronounced, the interhemispheric relations were impaired. The visual analysis revealed "flat" and "hypersynchronous" EEG types in patients. The dominant pathologic activity in the betal range indicative of mediobasal and oral brainstem lesions was characteristic of the flat EEG. This type of activity was observed in 60% of patients. In these cases, a general decrease in EEG coherence and temperature was most pronounced in the left hemisphere. The hypersynchronou EEG type (40% patients) was characterized by paroxysmal activity in the theta and alpha ranges suggesting diencephalic brain lesions. In these cases, EEG coherence and temperature were more variable; changes in the right hemisphere were significant, be it increase or decrease. Our complex approach to investigation of brain activity in different aspects seems to be promising in estimation of the brain functional state both in healthy persons and patients in remote terms after exposure to radiation. The specific hemispheric temperature changes revealed in Chernobyl patients especially during cognitive activity can be the sequels of postradiation disorders of vascular neuro-circulation. The EEG findings suggest subcortical disorders at different levels (diencephalic or brainstem) and functional failure of the right or left hemispheres in remote terms after exposure to radiation.

Electrophysiological and pharmacological characteristics of two types of spike-wave discharges in WAG/Rij rats.

Rats of the WAG/Rij strain are commonly seen as a genetic model for generalised absence epilepsy in man. Interestingly, generalised absence epilepsy shows, in addition to the fully generalised spike-wave discharges, a second type of spike-wave discharge, which lasts for a shorter time, has a lower frequency, and a lower incidence. The originally described distinction between the two types of spike-wave discharges was mainly based on the shape, polarity and duration of the discharges. In the present study other characteristics such as the spatial and temporal distribution of the spike and wave components of the two discharges and frequency spectra were found to differ between the two types. In addition, a reciprocal regulation of the two types of spike-wave discharges by drugs affecting the dopaminergic system (haloperidol and apomorphine) was observed. The results convincingly demonstrate the difference between the two phenomena and warrant the search for neurobiological mechanisms underlying both types of spike-wave discharges.

[Possible mechanisms for forming typological features of behavior of WAG/Rij line rats]. / Vozmozhnye mekhanizmy formirovaniia tipologicheskikh osobennostei povedeniia krys linii WAG/Rij.

Typological behavior reactions of WAG/Rij rats were studied from the standpoint of divergent modulatory integration hypothesis. This rat strain has a genetically determined dominant dysfunction of the benzodiazepine system of the thalamic nuclei. This disorder provokes an epileptiform disease such as absence epilepsy. It was suggested that the dysfunction of this system would result in a modification of the modulatory systems, which support the motivation states of escape and avoidance reactions as well as of the modulatory systems, which form the emotional states. Modifications of these states are the background of typological behavioral features of WAG/Rij rats. It was shown that WAG/Rij have the lower threshold of the development of haloperidol catalepsy, higher levels of fear and depression. On the first day of training in a shuttle box, WAG/Rij rats demonstrated better avoidance performance than Wistar rats. On the second and 28th days, the amnestic effect of the epileptiform disease was observed. The amnestic effect was also observed after passive avoidance conditioning. The results are discussed in terms of the modulatory integratin hypothesis.

The use of neural transplantation for suppression of seizure activity in genetically epilepsy-prone rats.

The possibility of correcting seizure activity with neural transplantation was studied in Wistar rats with audiogenic seizures and in Krushinskii-Molodkina rats with high level of audiogenic seizures. In Wistar rats seizures were absent during 24 weeks after combined bilateral transplantation of striatal and cerebellar tissue from newborn rats into the parietal cortex. The same transplantation performed in Krushinskii--Molodkina rats increased the latency of audiogenic seizures. In some rats the intensity of seizures decreased, but they did not completely disappeared. Suppression of seizure activity in Krushinskii-Molodkina rats was observed after transplantation of striatal and cerebellar tissue simultaneously into the parietal cortex and inferior colliculi.

[The mapping of spike-wave discharges in WAG/Rij rats (a genetic strain of absence epilepsy)]. / Kartirovanie razriadov pik-volna u krys linii WAG/Rij (geneticheskaia liniia absence-épilepsii).

The electrical activity of different cortical areas was recorded in 37 WAG/Rij rats under conditions of chronic experiment. The typical for absence epilepsy spike-wave discharges occur in EEG of all the animals of the strain. The average amplitude distribution maps were constructed based on the recording of two main components of the spike-wave discharge. The most frequently occurring discharges of 5-9 s in duration were taken for map construction. Separate maps were constructed for the beginning and for the end a discharge. It was shown that at the beginning of a discharge the maximum of spike amplitude was localized in the frontal cortical area in the site of localization of the eye, vibrissa and chewing movement centers. At the same time, the wave was better pronounced in the occipital cortical areas. At the end of a discharge spike amplitude diminished and the cortical square over which it was manifested was cut down. On the contrary, at the end of a discharge were amplitude increased and the area of its distinct recording spread to the frontal cortical areas. The wave amplitude maximum was observed over the cortical areas 17. The obtained evidence suggest the relatively independent spatio-temporal dynamics of the two main components of the spike-wave discharge complex.

Generalized absence epilepsy and catalepsy in rats.

Adult WAG/Rij rats are considered adequate genetic models for human generalized absence epilepsy. Rats of this strain of 8, 12, and 18 weeks old and age-matched control Wistar rats were exposed to sound stimulation. After offset of stimulation, all WAG/Rij rats showed cataleptic or even cataplexic reactions, which could persist for up to 20 min. Age effects could be demonstrated. None of the Wistar rats showed cataleptic reactions. Electroencephalographic studies in WAG/Rij rats of 21 weeks showed that spike-wave discharges were abundantly present in the background electroencephalogram prior to sound stimulation. Age-matched Wistar rats had almost no spike-wave discharges. Spike-wave discharges in WAG/Rij rats disappeared during sound stimulation and were then increased compared to the prestimulation and stimulation periods. The electroencephalogram during the cataleptic state was also characterized by the presence of large amplitude 2 Hz waves, interspersed with spike-wave discharges. The data suggest that the cataleptic state can be elicited in genetically epilepsy-prone rats. The youngest WAG/Rij rats showed no spike-wave discharges during the cataleptic state. In all, the data suggest that epilepsy-prone animals are sensitive for catalepsy at an age at which the EEG signs of generalized absence epilepsy are not yet manifest.

[The effect of neural transplantation on audiogenic seizures in rats of different genetic strains]. / Vliianie neirotransplantatsii na audiogennye sudorogi u krys raznykh geneticheskikh linii.

The effects of neurotransplantation on development of audiogenic seizures (AS) were studied in Krushinskii-Molodkina (KM) rats genetically predisposed to AS and in Wistar rats especially selected for AS. Within 24 weeks after bilateral combined transplantation of the newborn striatum and cerebellum into the parietal cortex, the AS didn't develop in Wistar rats in 74% of tests. In control Wistar rats with cortical grafts or saline injections into the parietal cortex there were no significant changes in the AS development. In the experimental KM rats the grafting led to the 4-5-times increase in the AS latency. In 50% of rats it decreased the AS severity by 1-2. In the control KM rats these parameters didn't change. It was concluded that it was possible to suppress or decrease the AS development by the transplantation of the newborn striatal and cerebellar tissue into the cortex of rats predisposed to this kind of seizures.