Interrelationship between the neocortex and limbic system in emotional stress and epileptiform syndromes

The paper describes bioelectrical correlates of negative emotional states on three models: 1) states caused by local, chronic electric stimulation of negative emotiogenic zones (in cats, rabbits); 2) by a neurogenic stress in rats resulting from a conflict of afferent excitations; 3) by an experimental syndrome--"expectation stress". The data attest that hypersynchronization of bioelectrical activity in limbic and cortical structures is a sufficiently significant correlate of an emotional stress. It is assumed that hypersynchronization reflects one of the general mechanisms of involvement of brain structures in a state of neurogenic stress and its manifestation.     

Effect of stimulation of "emotiogenic" brain structures on pyramidal tract responses

In experiments with stimulation of emotiogenic zones (lateral and medial hypothalamus, raphe nuclei), as a conditioning agent, a study was made of summary responses of the pyramidal tract to electrical stimulation of the sensorimotor cortex in immobilized and freely moving rats. The responses exhibited a positive early direct P-component (mean latency 0.8 +/- 0.3 ms) and a late synaptic N-component (mean latency 1.8 +/- 0.5). Reduction of the N-component amplitude was observed during stimulation of the lateral hypothalamus, and its enhancement during stimulation of the medial hypothalamus. Stimulation of the raphe nuclei produced variable, statistically non-significant changes. The experiments have shown that the identified pyramidal neurones tend to reciprocal reactions during stimulation of positive and negative emotiogenic structures. Inhibitory and excitatory influences of the respectively positive and negative emotiogenic structures on pyramidal neurones are due to indirect modulating actions on presynaptic structures.     

Shift of the catecholamine levels at stimulation of the hypothalamic emotiogenic zones

Using models of electrical self-stimulation of the positive emotiogenic zones and stimulation of the negative emotiogenic zones of the hypothalamus in rats, we demonstrated that both these stimulations increase the noradrenaline level in the frontal cortex. This shows a nonspecific nature of activation of the dorsal noradrenergic bundle, resulting from motivational excitation. When the frequency of self-stimulation reaction remained stable, activation of the dorsal noradrenergic bundle was moderate, and at decay of the above reaction it returned to the control level. Behavior connected with activation of the motor functions was characterized by an increase in the dopamine and noradrenaline levels in the caudate nucleus. In theglobus pallidum, the dopamine content changed only under conditions of stimulation of the negative emotiogenic zones: these were an increase in the reaction of active avoidance and a decrease in passive avoidance.     

Normalization of the stress-induced cardiac rhythm disturbances by activation of the positive emotiogenic area of the lateral hypothalamus in the rabbit

Results of experiments indicated, that activation of the positive emotiogenic areas of the lateral hypothalamus abolished what may be considered emotionally induced cardiovascular disturbances. The by immobilization and hypothalamic defence area stimulation provoked increase of blood pressure and heart rate returned to control values, the giant T waves of ECG and dysrhythmias if present disappeared. The morphological abnormalities in the subcellular structures of the myocardium due to prolonged stress stimulation, could not be annulled by the evoked positive emotions. On the other hand the activation of the positive emotiogenic area of the hypothalamus preceded and overlapped with that of the defence area and immobilization, it prevented the functional as well as morphological cardiovascular changes.     

Reflection of the Emotional Significance of Visual Stimuli in the Characteristics of Evoked EEG Potentials

Healthy subjects (n = 88) were asked to passively visualize positive and passive emotiogenic visual stimuli and also stimuli with a neutral emotional content. Images of the International Affective Picture System (IAPS) were used. Amplitude/time characteristics of the components of evoked EEG potentials (EPs), P1, N1, P2, N2, and P3 and topographic distribution of the latter components were analyzed. The latencies, amplitudes, and topography of the EP waves induced by presentation of positive and negative stimuli were found to be different from the respective values for the EPs induced by neutral stimuli. The level and pattern of these differences typical of different EP components were dissimilar and depended on the sign of the emotions. Specificities related to the valency of an identified stimulus were observed within nearly all stages of processing of visual signals, for the negative stimuli, beginning from an early stage of sensory analysis corresponding to the development of wave Р1. The latencies of components Р1 in the case of presentation of emotiogenic negative stimuli and those of components N1, N2, and Р3 in the case of presentation of the stimuli of both valencies were shorter than the latencies observed at neutral stimuli. The amplitude of component N2 at perception of positive stimuli was, on average, lower, while the Р3 amplitude at perception of all emotiogenic stimuli was higher than in the case of presentation of neutral stimuli. The time dynamics of topographic peculiarities of processing of emotiogenic information were complicated. Activation of the left hemisphere was observed during the earliest stages of perception, while the right hemisphere was activated within the intermediate stages. Generalized activation of the cortex after the action of negative signals and dominance of the left hemisphere under conditions of presentation of positive stimuli were observed only within the final stages. As is supposed, emotiogenic stimuli possess a greater biological significance than neutral ones, and this is why the former attract visual attention first; they more intensely activate the respective cortical zones, and the corresponding visual information is processed more rapidly. The observed effects were more clearly expressed in the case of action of negative stimuli; these effects involved more extensive cortical zones. These facts are indicative of the higher intensity of activating influences of negative emotiogenic stimuli on neutral systems of the higher CNS structures.     

Synaptic reactions of sensomotor cortex neurons to stimulation of emotionally significant brain structures

The study deals with synaptic and spike responses of neurones in the rat sensorimotor cortex to stimulation of the lateral and medial hypothalamus, locus coeruleus and raphe nuclei. The activity of 57 neurones was recorded, 41 of them intracellularly and quasi-intracellularly, in response to the stimulation of sites in these structures, which were previously identified as "emotionally/ significant. No considerable differences in the effects of the stimulation of different "emotiogenic" zones were found. The stimulation parameters, differing from the "behavioural" ones by a greater strength, elicited in the majority of neurones clear post-synaptic responses, often in the form of EPSP-IPSP. Latencies of the responses varied from 3 to 80 msec. The most stable and pronounced responses were obtained to the stimulation of the lateral hypothalamus. No significant correlations of the latencies of the responses to the stimulation of different "emotiogenic" structures were found.     

Participation of adrenal hormones in the genesis of arterial hypertension of hypothalamic origin]

Continuous many-hour stimulation of the hypothalamic negative emotiogenic centres (ventromedial nuclei) evoked a stable arterial hypertension with a peculiar phasic dynamics of the adrenal secretory activity in waking immobilized rabbits. Bilateral extirpation of the adrenal glands decreased the initial level of the average arterial pressure, inhibiting development of stable arterial hypertension. Many-hour stimulation of the mentioned structures also produced stable arterial hypertension in adrenalectomized rabbits if preceded by the administration of hydrocortisone together with adrenaline. Against the background of separate administration of hydrocortisone and adrenaline to adrenalectomized rabbits, many-hour stimulation of the ventromedial hypothalamus evoked a short-term rise in the arterial pressure. A conclusion was drawn that activation of hormones of the adrenal cortical and medullary layers played an important part in the formation of stable arterial hypertension in rabbits under continuous many-hour stimulation of the hypothalamic negative emotiogenic centres.     

Behavioral reactions to stimulation of the emotiogenic zones of the brain in the rats with different individual experience

Emotional reactions evoked by electric stimulation of the hypothalamus and amygdala were studied in white outbred rats, grown either in conditions of isolation or in community. The method of self-stimulation in shuttle box was used. The values of self-stimulation reaction were significantly lower and those of avoidance reactions were higher in animals bred in isolation. Their food-procuring behaviour disappeared faster at stimulation of the negative emotiogenic zones. The observed differences are due to plastic reorganization of the brain reinforcing systems.     

Effect of positive and negative emotional states on the electrical activity of the auditory cortex in rabbit ontogeny

It has been shown that in all age groups of animals, self-stimulation of the hypothalamus is accompanied with the decrease in the latent period and the increase in the amplitude of the evoked potential (EP) in the auditory cortex. During negative stimulation, the increase in temporal parameters of the response takes place together with the decrease in the amplitude of the EP and the onset of secondary waves. Significant age changes were revealed in the recovery of the initial pattern of the EP after cessation of stimulation of emotiogenic zones. The recovery of the EP after stimulation of the "reward" zone in younger rabbits occurs 4 times faster than in adult animals, whereas in the former the recovery period of the EP after stimulation of the "punishment" zone is significantly longer.     

Features of the morphofunctional state of the organs of the thymico-lymphatic system during various adaptive reactions induced by electric stimulation of emotiogenic structures of the brain

Weak electrical stimulation of emotiogenic brain structures was found to lead to the development of different general non-specific adaptation reactions. Stimulation of nucleus lateralis septi was found to evoke mainly the development of activation reaction, while stimulation of globus pallidum caused primarily the development of training reactions. Stress reactions were considerably less frequent in electrical stimulation of both kinds of structures than in the control. This can be explained by small values of the electrical current applied. Morphofunctional activity of thymus lymphatic system depended not only on the type of non-specific reaction but also on the character of the stimulated emotiogenic structure--the functional activity was higher with the stimulation of nucleus lateralis-septi. However, the functional activity of thymus lymphatic system in rats with globus pallidum stimulation was higher than in control rats that were not subject to any stimulation.     

The dynamics of the electrical activity of the forebrain structures in rats in the waking-sleep cycle after electrostimulations of the emotiogenic zones in the lateral hypothalamic area]

One series of ES (multiple priming) of emotion-positive zone (1) ore the ambivalent zone (2) of lateral hypothalamus (LH) during one hour in Wistar male rats resulted in disorders of the W-S cycle: reduction of deep slow-wave sleep down to about 4.7% (zone 1) and down to 0.9% (zone 2), as well as a considerable reduction of REM sleep down to 0.8% (zone 1). The results of the analysis of bioelectrical brain activity dynamics in the W-S cycle suggest that hyperactivation of emotiogenic zones generated by ES is responsible for the establishment of paroxysmal states corresponding to the second and the third stages of kindling and the disorders of the W-S cycle. Kindling is assumed to form due to emotiogenic zones of the brain involved in to this process. The longer bursts of hypersynchronous bioelectrical activity in the cortex than in the subcortical structures during transient stages of sleep may be in favour of more active participation of phylogenetically younger brain structures in the process of epileptogenesis.     

Effect of morphine on the concentration of monoamines in the emotiogenic zones of the hypothalamus in adult and old rats

The content of monoamines in the emotiogenic hypothalamic zones has been shown to noticeably change with aging of rats. The level of noradrenaline and serotonin increased in the ventromedial nucleus of the hypothalamus, while the concentration of noradrenaline increased in the lateral hypothalamic zone. Single i.p. injections of 10 mg/kg morphine evoked qualitatively different shifts in the monoamine concentrations in the hypothalamic emotiogenic zones of the rats of different ages: the level of dopamine increased in adult animals, while the levels of noradrenaline and serotonin dropped in old rats. It is supposed that in old age the effect of morphine on dopaminergic structures in the emotiogenic hypothalamic zones becomes more moderate, whereas that on the noradrenergic and serotonergic structures is facilitated. The age-related specificities of the morphine effect on the monoaminergic regulation of the emotiogenic hypothalamic zones can determine considerable modifications of a psychotropic effect of the drug in old age.     

Relation of alcoholic motivation to the functional state of the emotive zones of the brain in rats

Reactions of neurones pair of positive and negative emotiogenic hypothalamus zones to electrocutaneous stimulation and to intraperitoneal administration of ethanol solution (2 g/kg) were studied in outbred male rats with previously determined attitude to alcohol. In animals who preferred alcohol the neurones of the negative zone were significantly more reactive, and in animals who preferred water the neurones of the positive zone were more reactive. In both studied groups of rats, in most cases ethanol had an inhibitory influence on impulse activity of negative zone neurones, but it acted differently on positive zone neurones: in most cases it intensified neurones impulse activity in rats preferring alcohol and significantly inhibited it in animals rejecting alcohol.     

Peculiarities of Formation and Reversibility of Neurogenic Stress-Related Emotional Disorders in Rats

In experiments on rats, we modeled neurogenic stress-induced emotional disorders (stress was evoked by repetitive nociceptive stimulation) and studied their peculiarities within the stressory and post-stressory periods. In these animals, drastic changes in the brain electrical activity and emotional behavior gradually developed; such changes were manifested over a long time period after cessation of the stressory influences. Our experiments demonstrated that tight and stable interrelations among brain limbic structures and negative hypothalamic emotional centers are formed under conditions of prolonged action of emotional stress. This results in the development of a protracted state of negative emotional excitation. The hippocampus is considered one of the key limbic structures responsible for the development of stable pathological stress-related reactions of the brain. Within the post-stressory period, we observed dramatic worsening of the general functional state of the animals, which developed in a parallel manner with intensification of the activity of the negative emotiogenic brain system. It is probable that the existence of periods of unstable equilibrium between oppositely directed emotional reactions in the dynamics of stress and after cessation of stressory influences is a common rule. Such periods reflect peculiarities of rearrangements in the adaptive brain mechanisms under conditions of a stable change in the mode of brain functioning in one particular situation or another.     

Interhemispheric asymmetry in the functional organization of the prefrontal cortex in animals of different typologic groups

Rats allocated to groups by the method of "emotional resonance": rats which did and did not escape crying of a partner (A- and E-groups, respectively). Unit activity in the right and left prefrontal brain cortex (PFC) was recorded in these rats. The recorded neurons neurons were divided in two groups according to their reaction to a change in the level of food motivation. The so-called D-neurons decreased their activity after feeding of animals after a 24-hour food deprivation and the other group (I-neurons) increased its firing rate rate in this situation. It was shown that hemispheric distributions of D- and I-neurons are different in selected rat groups. In E-rats the I-neurons substantially predominated in the left hemisphere, whereas the D-neurons were more frequently recorded in the right one. No such asymmetry was observed in A-group of rats. During intracranial stimulation of emotionally positive brain structures I-neurons increased their firing rate, predominantly, in the left hemisphere, whereas during intracranial emotionally negative stimulation activation of the D-neurons predominated at the right. Features of the observed functional interhemispheric asymmetry of prefrontal cortex in A- and E-groups of rats were explained by differences in the interaction between hemispheres and dissimilar activation control.     

Assessment of the reinforcing properties of self stimulation in rats using the "discordance" index]

Histogramms of the duration of pedal pressing (PDH) as a function of stimulation parameters, were studied in fifteen rats with electrodes inserted in the lateral hypothalamus and with fixed series of brain stimulation. The "discordance" parameter was used to estimate the changes in PDH modes relative to the moment of the end of brain stimulation. It was found that an increase in the stimulation charge brought about a gradual replacement of positive discordance (the duration of pressing exceeds that of stimulation) by a negative one (duration of pressing is shorter than that of stimulation) and a rise of negative discordance. It is assumed that in the case of positive discordance the duration of the total brain stimulation possesses reinforcing properties, while in the case of negative discordance the beginning of the stimulation possesses reinforcing properties, and its continuation becomes negative.     

Effect of stimulation of the reticular formation on the motivational and reinforcing effects of the self stimulation zones

The influence was studied on the midbrain reticular formation (RF) on motivational and reinforcing effects of stimulation of the same selfstimulation zones (SS) of hypothalamic area. A current of gradually increasing intensity was used, by means of which three groups of functionally (behaviourally) specific reticular points were revealed: motivationaly neutral, positive and negative. The data obtained show that influences of RF on SS zones of hypothalamus differand depend on functional properties of various RF areas. Changes of motivational effects in SS zones reflex the specificity of reticular foci in a lesser degree than changes in reinforcing effects. It has been suggested that reinforcing effects of the SS hypothalamic zones possess their own activating mechanism specifically related to its "positive" link and differing from reticular mechanism of unspecific activation.     

The effect of electric stimulation of several zones of the brain on verbal memory in humans]

Investigations of patients with implanted in intracerebral electrodes have shown that within some subcortical structures there exist neuronal-glial populations in which the dynamics of their functional state, according to the results of local recording of slow processes (oxygen tension, local blood flow, impedance), clearly correlates with the correct performance of the tests on operative memory. Electrical stimulation of some of the zones significantly changes the volume of operative memory and influences the general state and higher psychic functions in the patients. The result of electrical stimulation of the brain is determined by the role of different zones in the mnestic act and by the stage at which the stimulation is performed. The role of the cerebral zones is discussed in which the change of the functional state correlated with errors in tests reproduction, the detectors of errors in securing human memory.     

Effect of prolonged alcoholization on the cerebral electical activity and emotional behavior of rats

Two stages of alcohol intoxication were detected in an experiment on 21 rats during formation of addiction to alcohol. It has been shown that the emotiogenic hypothalamic zones may play the part of trigger mechanisms with infolvement of limbic and neocortical apparatuses. At the same time a different type of integration of addiction to alcohol food is possible, in which the emotiogenic zones do not play the principal part. The late stages of formation of addiction to alcohol are characterized by EEG hypersynchronia with a qualitatively different structure in the periods of abstinence and "saturation" with alcohol. A close connection has been recorded between the mechanisms of emotion, hypersynchronia and behavioral epileptic phenomena.     

Analysis of the effect of increasing electrodermal stimulation on the somatovegetative reactions evoked by stimulation of the ventromedial hypothalamus

The influence of increasing electrodermal stimulation (EDS) on the dynamics of the somatovegetative reactions evoked by electrical stimulation of negative emotiogenic regions of the hypothalamus was studied. EDS produced a blocking effect on the somatovegetative reactions evoked by stimulation of the ventromedial hypothalamus (VMH). Pretreatment with naloxone prevented the effects of EDS. Injection of beta-endorphine in a dose of 10 micrograms to the lateral ventricules of the animal brain also blocked the somatovegetative reactions during VMH stimulation. Injection of beta-endorphine in doses of 50-100 micrograms enhanced and prolonged the somatovegetative reactions evoked by VMH stimulation. Elevated arterial blood pressure, pronounced bradycardia, extrasystoles, muscle tremor, and pathologic respiration were recorded. These disorders were completely reversed by EDS. It is assumed that both opiate peptides and their receptors are involved in the mechanism of the somatovegetative reactions evoked by VMH stimulation, experiencing the influence of EDS.