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.     

Changes in the somatosensory evoked potentials in the night sleep of healthy subjects under conditions of preceding emotional stress

Somatosensory evoked potentials (SEP) were studied in eight healthy subjects in a state of alertness, in different stages of night sleep and also in night sleep after previous emotional stress. Characteristic changes of SEP were revealed in the second stage of sleep in delta-sleep and in the phase of rapid sleep. In conditions of emotional stress changes in SEP characteristics in periods of alertness and of night sleep were observed, expressed in the amplitude increase of a number of components. Asymmetry was revealed with predominance of the amplitude increase in the right hemisphere in the phase of the rapid sleep testifying to different roles of the cerebral hemispheres in processing of emotionally significant information. SEP changes in different functional states after the influence of emotional stress were considered as the reflection of non-specific activation increase possibly due to activation of the limbic structures in response to stress-producing stimulus.     

Electrical activity of the limbic structures of the dog brain during simultaneous stimulation of the cingulate gyrus and hypothalamus]

Simultaneous electrical stimulation of the anterior part of the cingulate gyrus and the anterior-lateral part of the hypothalamus in the dog brought about EEG synchronization in the limbic system structures and increased correlation coefficients between them. The animal's behaviour exhibited positive emotionally reactions (licking, sniffing, wagging the tail), attended with slowing of the heart rate. The indicated changes directly depend on the degree of emotional stress (the changes are more pronounced in hungry than in sated animals). Simultaneous stimulation of the anterior part of the cingulate gyrus and the anterior-lateral part of the hypothalamus apparently activates a system which reduces the level of emotional stress.     

Sexual dimorphism in reactions to stress during regular and altered photoperiods

Sexual dimorphism of rats in response to physiological stress influences was discovered. The emotional stress in female animals caused a sharp intensification of synthesis and corticosterone secretion, while in males there was an increase only in hormone synthesis and not its secretion. Females are more sensitive even to short-term changes in photoperiod. Stress reaction in females under conditions of three-day light depressed sharply and increased under conditions of three-day darkness. Stress reaction in males did not change under these conditions. The reactivity of adaptation system in females shortens the period of adaptation to the altered illumination regimen, which is manifested in the restoration of typical stress reactions. In males, refractoriness to weak stress influences lengthens the period of adaptation, which is manifested in the suppression of typical stress reaction observed in males.     

Effect of neurotensin on the behavior of rats with damaged serotoninergic neurons under immobilization stress

It was shown that the immobilization of animals has led to reducing of vertical and horizontal locomotor activity in the "open field" and decreasing of number of conditioned food-procuring reactions into T-maze. The damages of serotoninergic neurons produced via local injections of selective neurotoxin 5, 7-dihydroxytriptamine into dorsal raphe nucleus intensified behavior alterations. Neurotensin administrations reduced effects of neurotoxin: the rats locomotor activity and quantity of conditioned reactions into T-maze were kept at the phone level just after immobilization as well as next two days. The results indicate the important protective significance of neurotensinergic brain structures for ensuring of adaptive behavior of animals with damaged serotoninergic neurons under emotional stress conditions. It is supposed that neurotensin normalizing influences on behavior is connected to a restoration of balance of dopamine-and serotoninergic brain structures interaction.     

Immediate-early genes in the cerebral mechanisms of emotional stress

Immediate-early genes (IEGs) induction is one of the primary neuronal responses to emotional stress. In experiments with different types of stressors the brain structures with the most pronounced immediate early genes expression were identified. Biochemical, physiological and genetical mechanisms of the IEGs expression in the central nervous system during emotional stress are discussed in the article. Investigation of characteristics and conditions of the IEGs induction showed that immediate early genes induction is crucial for organization of neuroendocrine and hormonal responses during emotional stress. In situations that require adaptation and learning IEGs induction in brain is especially strong. The present data permit us to think that immediate early genes participate in formation of the long-lasting circulation of the negative emotional excitation in limbic system. Animals resistant and predisposed to psycho-emotional stress have different patterns of IEGs expression in conflict situations leading to emotional stresses. Immediate-early genes induction is especially pronounced in brains of sensitive to stress individuals. It is proved that differential approach with regard to individual differences in IEGs expression is preferential in emotional stress research. Neglect of this fact has led to contradictions in results of various authors. The investigation of the IEGs properties can help to define prospective ways of the effective coping with emotional stress and prevention of its dangerous consequences.     

Delayed effects of neurotensin microinjections into the substantia nigra on conditioned motor reactions of rats with lesions to serotoninergic neurons

Behavioral effects of neurotensin microinjections into the brain substantia nigra of rats with neurotoxic (5,7-dihydroxytryptamine) lesions of serotoninergic neurons in the dorsal raphe nucleus were studied. It was shown that neurotensin facilitated extinction of conditioned and intertrial reactions to negative (unreinforced) stimuli, but did not change the actualization of positive (with water reward) conditioned signals. Neurotensin-induced effects persisted in subsequent experiments without injections of the peptide. Neurotensin injections reduced the negative emotional states of lesioned animals in the arena during testing conditioned preference. It was concluded that the behavioral effects of neurotensin can be explained by the formation in the lesioned animals of the situational emotional state facilitating adaptive brain functions.     

Effects of stress and alcohol consumption on emotional/motivational behavior of rats and their first generation offspring

Neurophysiological manifestations of formation of the dependence on ethanol under stress conditions were studied in rats and their first generation offspring. In chronic experiments on 32 male rats, emotional stress was modeled (induction by nociceptive electrocutaneous stimulation), and an increased addiction to ethanol was formed. In these animals and in the first generation of their offspring (obtained from the above males and intact females), we studied emotional/motivational behavior, recorded the mass electrical activity from different brain structures, and measured the arterial pressure. In stressed rats, which acquired attraction to ethanol, negative emotional responses became transformed into positive, and behavioral and electrographic manifestations of the seizure activity developed. In the first generation offspring, the pattern of central rearrangements in the mechanisms of emotional/motivational behavior was to a great extent similar to that in parent rats.     

The possibility of elaborating conditioned reflexes on the basis of emotional reactions evoked by electrical stimulation of limbic structures]

In experiments on cats with chronically implanted electrodes a conditioned stimulus (200 c/s tone) was paired with electrical stimulation of limbic structures, which produces pronounced emotional behaviour: defensive, aggressive, alimentary or drinking reactions. It has been shown that conditioned reactions are not elaborated on the basis of electrical stimulation, which activates alimentary, drinking or aggressive behaviour. Neither is a conditioned reflex formed to the combination of sound and stimulation of the brain structures, which inhibits alimentary behaviour. A distinct conditioned fear reaction sets in as a result of combination of sound and electrical stimulation of brain structures, which evoke defensive behaviour. The data obtained are analyzed in the light of the significance of natural requirements of the organism for the elaboration of conditioned reflexes.     

Chronic Stress- and Sex-Specific Neuromorphological and Functional Changes in Limbic Structures

Chronic stress produces sex-specific neuromorphological changes in a variety of brain regions, which likely contribute to the gender differences observed in stress-related illnesses and cognitive ability. Here, we review the literature investigating the relationship between chronic stress and sex differences on brain plasticity and function, with an emphasis on morphological changes in dendritic arborization and spines in the hippocampus, prefrontal cortex, and amygdala. These brain structures are highly interconnected and sensitive to stress and gonadal hormones, and influence a variety of cognitive abilities. Although much less work has been published using female subjects than with male subjects, the findings suggest that the relationship between brain morphology and function is very different between the sexes. After reviewing the literature, we present a model showing how chronic stress influences the morphology of these brain regions and changes the dynamic of how these limbic structures interact with each other to produce altered behavioral outcomes in spatial ability, behavioral flexibility/executive function, and emotional arousal.     

Effect of mexidol on status of conditioned reflex activity after traumatic brain damage

Even partial hippocampal lesions in rats resulted in a disturbance of time interval determination over the course of several months (1200-1500 presentations) other complex conditioned reactions being preserved. As distinct from the control animals, the long period of failure of time interval counting was absent in rats receiving Mexidol. Continuous time conditioning took place in these animals. Due to substantial improvement of autonomic processes and emotional reactions, it was possible to present a higher number of conditioned stimuli in experiments. Mexidol seems to improve the compensatory and recovery processes after brain injuries: the impaired functions recover faster, the rate of the retrograde degeneration in the lesioned brain structures decreases, phenomena like Monakov's diaschis are not observed etc.     

Regional cerebral blood flow in the dorsal hippocampus of rats with informational pathology of behavior

The local cerebral bloodflow (LCBF) was studied by the hydrogen clearance technique in the dorsal hippocampus (DH) of rats with a deep stage of the informational pathology of behavior (IPB). The IPB was produced by the chronic negative emotional stress developed during the long period of testing delayed reactions (indirect variant: delay in 2-3 s) under conditions of time deficit between the signals (30 c) and high motivation level. A significant decrease in the LCBF level was demonstrated in the experimental group in comparison with the control animals. It is suggested that: (1) the decrease in the LCBF in the DH may be of a secondary character as a result of suppression of the functional activity of the DH by exposure to the chronic negative emotional stress; (2) it is not inconceivable that the LCBF decrease in the DH is of a primary character and may account for the dysfunction of this structure facilitating the emotional stress and its acquisition of pathogenic properties, thus being an important factor of the IPB formation.     

Linguistic features of the structure of verbal expression in emotional stress]

Comparative analysis was carried out of the linguistic characteristics of oral speech, recorded in 68 subjects in a state of anxiety (students in examination situation; surgical patients in preoperative interview; air force operators undergoing responsible professional-proficiency tests) and of speech disturbances in patients with damages in the parts of the brain which play a significant role in the control of stress and emotional behaviour. The results obtained allow to conclude, that speech disturbances of normal subjects in a state of anxiety are caused by physiological factors and thus can be used as objective indices of the speaker's emotional state, since they are similar to those of the patients with damages in the region of the temporal lobe, intimately connected with limbic structures.     

Participation of angiotensin II in the establishment of negative emotional reactions

In waking rats and rabbits systemically injected angiotensin II was shown to participate predominantly in the mechanisms of negative emotional reactions. The effects of angiotensin II were observed at the behavioural level as well as at the neuronal one. Depending on the dose and the time of injection of angiotensin II and its specific antagonist saralasin they inhibited or facilitated elaboration and extinction of automatized conditioned active avoidance independently of arterial, pressure changes, the pain threshold being altered. Injection of angiotensin II abolished individual behavioural reactions of the animals in response to stress factors and increased their resistability to emotional stress. The negative emotional reactions were found to induce changes of chemosensitivity of neurones of the parafascicular complex of the medial thalamus and the midbrain reticular formation during microionophoretic application of angiotensin II. A supposition is made about the increase of angiotensin II brain synthesis under conditions of emotional stress.     

Effect of diazepam on the formation and reproduction of conditioned cortical reactions in man

Intramuscular injections of seduxen (10 mg), a benzodiasepin drug, with expressed tranquilizing and alarm suppressing effects, were used with the aim of experimental testing of a hypothesis on the neural mechanism of conditioned changes of the P300 wave. Under the action of seduxen no temporary connections could be formed between a perceived nonverbal visual stimulus and a unrecognized emotional word. The seduxen did not suppress the conditioned cortical reaction acquired due to combination of nonverbal stimulus with unrecognized emotional word. The suggestion is made that the necessary condition of temporary connection elaboration by means of a unrecognized verbal stimulus is the implication of the limbic structures where negative emotional reactions are integrated.     

Interrelations between the contents of transmitter amino acids in the brain structures and the level of convulsion readiness in rats

In rats with high and low levels of the audiogenic excitability (68 and 62 animals, respectivels, we measured the thresholds of convulsive reactions elicited by electrical stimulation of a few limbic and brainstem structures. The obtained figures were compared with the those of the levels of transmitter amino acids (glutamate, aspartate, glycine, and taurine) measured in the same brain structures in corresponding groups of the animals (80 rats in each group. It was found that the thresholds of convulsive reactions evoked by electrical stimulation of most tested brain structures are lower in the audiogenically excitable animals than those in the animals with high thresholds of the audiogenic excitability. These dissimilarities demonstrated certain correlation with increased glutamate concentrations in some structures under study and, probably, to a considerable extent depended on a deficiency of inhibitory amino acids, glycine and taurine, in most tested brain structures.     

THe age-related characteristics of interhemispheric asymmetry during the perception of verbal information by stuttering children]

Age peculiarities of functional brain asymmetry in perception of emotional information of the speech have been revealed. It was shown that the age of 4-7 years is the most important period in ontogenesis for the age dynamics of functional brain asymmetry in perception of emotions. It is in this particular age that functional reorganization of perception in stuttering children is observed. The revealed disturbances in functional brain asymmetry indicate that correction of emotional activity in stutterers should be made during early periods of ontogenesis.     

NADH-vanadate-oxidoreductase in emotional-pain stress and its possible role in the regulation of Na+-K+-ATPase activity

It is established that NADH-vanadate-oxidoreductase in brain and heart changes its activity depending on the period of the emotional pain stress (EPS) development. In early acute period of EPS (to 48 hours) NADH-vanadate-oxidoreductase is activated in the brain, while in the heart its activity lowers in comparison with normal animals. In the later period after EPS the stimulation of NADH-vanadate-oxidoreductase activity in the both organs in observed. This dynamics creates possibilities for different accumulation of such Na+,K+-ATPase inhibitor as vanadate (VO3-) in the heart and brain. An increase of pO2 of the blood, probably, influences the enhancement of the VO3- concentration in the blood and organs.     

c-fos Gene expression during emotional stress in rats: blocking by delta sleep-inducing peptide

An emotional stress induces an obvious immediate early gene c-fos expression in the brain limbic structures in the rats predisposed to emotional stress. Administration of the delta-sleep-inducing peptide (DSIP) was shown to inhibit the c-fos expression. It led to an obvious inhibition of the c-fos expression in paraventricular nuclei of the hypothalamus, medial and lateral parts of the septum of rats predisposed to emotional stress. This mechanism seems to play an important role in the DSIP anti-stress effects.     

The exploratory behavior in an open field and in a burrowing chamber of rats with different predispositions to stress]

The peculiarities of oriental research behavior and correlation between activities of catecholaminergic and serotoninergic brain systems dependently on their stress resistance degree were investigated in Wistar rats. The experiments showed that resistant (R) to a sound stimulus rats differed from nonresistant (NR) ones by increased research activity under moderate stress in the open field test and by decreased research behavior level in the cell chamber test. The biochemical analysis of biogenic amines in different brain structures revealed increased norepinephrine levels in stress R rats, and increased dopamine and serotonin levels in NR ones. The findings suggest that inborn behavior regulation in animals with different stress resistance is determined by different correlations between serotonin-dopamine and norepinephrine brain systems activities.