Formation of epileptic activity complexes in the cerebral cortex as a result of a determinant focus induced by acetylcholine]

Foci of increased excitability were created by means of weak strychnine and penicillin dilutions in experiments on cats. These foci worked at individual regimens. Creation with acetylcholine and proserine of a hyperactive focus led to increase of the amplitude and frequency of convulsive discharges at first in the nearest activity foci, and then in the ones remote from the hyperactive focus. The next stage was attended by qualitative changes in the activity pattern of strychnine and penicillin foci (the appearance of acetylcholine activity in them) and by the formation of a single functional focal complex working in the regimen of acetylcholine focus. Thus, the latter played the role of a determinant structure. Suppression of the determinant focus activity led to disappearance of the acetylcholine activity in all the other foci, restoration of the initial (penicillin and strychnine) activity, and to the epileptic complex decay.     

Formation of epileptic activity complexes under the effect of the determinant focus in the cortex isolé]

In experiments on cats foci of enhanced excitation working in independent regimes were created in the neuronal-isolated cortex using weak strychnine solutions. Creation of a hyperactive focus by means of application of strychnine concentrated solutions or crystals leads to an increase in the amplitude and discharge frequency in other foci, synchronism in discharges of these foci and their unification into a single functional complex, working in the hyperactive focus regime. The latter, in such a way, presented the determinant structure. Under the influence of the determinaant focus there was also a marked generalization of the convulsive activity manifested by an embrace with epileptical discharges of the cortex area intact from strychnine. The results obtained indicate that the established relations between the foci of hyperactivity in the cortx as well as the effects of the determinant structure may be realized by the cortex mechanisms proper.     

Effect of nicotinamide on epileptic activity in the cerebral cortex

The experiments on cats showed that intravenous administration of nicotinamide suppresses the epileptic activity in a solitary epileptic focus as well as in the complex of epileptic foci produced by strychnine application to various cortical zones under the influence of the most powerful focus that plays the role of a determinant. After the intravenous injection of nicotinamide (50-70 mg/kg) the complex was destabilized and broken down. The epileptic activity in the dependent foci of the complex disappeared first in the more remote from the determinant focus and then in the nearer one. The determinant focus was the last to disappear. The inhibitory effect of nicotinamide is associated with antiepileptic activity. Nicotinamide is suggested to be one of the endogenous drugs which may suppress brain hyperactivity and activate the antiepileptogenic system.     

Interaction between two excitation foci in the central nervous system capable for summation

The interaction between two dominant foci was carried out on different models of dominant. It was shown that the following pairs: latent motor and blinking excitation foci; hunger and hypnotic dominants, decaying polarization dominant (related with functioning of the left-hemisphere) and hypnotic dominant can function simultaneously. After repeated formation of a new dominant focus against the background of the existing stable dominant created earlier, a replacement of dominants takes place. This process passes through the stage of formation of the latent dominant not yet apparent at the behavioral level but with the electrical activity typical for the dominant focus. Actually, two dominants exist at this stage: the previous active and latent foci. The latter determines further behavior of the animal.     

Changes in the spectrum of LDH isoenzymes in foci of epileptic activity induced by penicillin in the cerebral cortex of rats

The correlation between electrophysiological changes and isozymes of LDH of the rat brain cortex was studied in seizure foci induced by application of sodium penicillin. It was discovered that activity of LDH1 was suppressed, and that of LDH5 fraction was elevated in the determinant focus, which indicates the enhanced glucose anaerobic transformation. The spectrum of LDH isozymes did not practically differ from the indicators in control animals in a homotopic region of the contralateral hemisphere prior to creation of the mirror focus. The anaerobic processes were found to be increased in the mirror focus and in the determinant one as well. Similar pattern of changes in electrophysiological and neurochemical characteristics in the determinant and dependent mirror foci attests to the formation of a pathological system out of the two epileptic foci.     

Effects of anticonvulsant agents and ethanol on the complexes of epileptic foci created by applications of bicuculline, strychnine, and penicillin in the rat brain cortex

Anticonvulsive effects of direct agonists of the GABA receptor system, medinal and phenazepam, as well as ethanol, on the complexes of epileptic foci created in the rat brain cortex by applications of various convulsant agents (bicuculline, strychnine, or penicillin) were studied. Ethanol, as well as phenazepam and medinal, were shown to possess high anti-epileptic activity in relation to the complexes. It was shown, using an i.v. infusion technique, that threshold doses of strychnine and bicuculline depend, in a linear and a nonlinear fashion, respectively, on the alcohol doses administered. A specific feature was found in the pharmacolgoical effect of ethanol: anticonvulsive activity of ethanol was pronounced within the postinjection interval from 5 min to 4 h, while within the following interval, from 4 to 24 h, the animals turned into a seizure-ready state. The subseizure phase was observed under the conditions when the penicillin complex was induced, and also following i.v. injections of strychnine and bicuculline.     

Levels of consciousness and levels of activation

In the paper Pavlov's idea is used about "the bright spot of consciousness" as a zone of increased excitability which moves over the cerebral cortex. Zone of increased activation is revealed migrating from the frontal parts of the left hemisphere to the occipital parts of the right hemisphere. By means of various methods (record of amplitude and latency of the visual evoked responses, frequency and amplitude of the dominant rhythm, spectral-coherent analysis of the electroencephalogram) the activation of focus in the cerebral cortex was singled out, which moved, depending on the novelty, complication and degree of automatization of the task, from the frontal parts of the left hemisphere to the occipital parts of the right hemisphere. A parallel is drawn between Pavlov's hypothesis on the focus of consciousness as foci of increased brain activity, and revealed foci of activation. The conclusion is made about fluctuations of consciousness level as a factor which is in the basis of activation focus migration.     

Effect of damage to the zone of the medial forebrain bundle and preoptic area on the activiy of a penicillin-induced epileptiform focus (phenomenon of the hyperactive determinant dispatch station)]

It was shown in experiments on cats under nembutal anesthesia that a lesion of the medial forebrain bundle (MFB) and partly of the preoptic region at the side of local penicillin application on the cerebral cortex (g. suprasylvius medius) results in depression of the epileptiform activity in the penicillin-induced focus, as well as in the secondary "mirror" focus, which appeared in the symmetrical cortex area of the other hemisphere. The MFB lesion at the "mirror" focus side led to depression of the seizure spike potentials in this focus only and did not change the activity in the primary epileptiform one. The described effects are considered from the aspect of the conception on the role of the determinant dispatch station (DDS) in the central nervous system: the primary epileptiform focus plays the role of the hyperactive DDS which induces the secondary focus and determines the character of its activity. The results of the study substantiate a suggestion that the MFB can take part in the modulation of the cortical epileptiform activity.     

Mechanisms of transmission of excitation grnerated in the orbito-frontal cortex]

Experiments carried out on cats showed that interhemispheric generalization of strychnine spasmodic potentials from the orbito-frontal cortex were mainly brought about by the callosal pathway. In contrast to other projection and association zones of the cortex only the frontal portion of the corpus callosum (the rostrum) and not the whole corpus took part in transmitting strychnine commissures. The results of investigations carried out were consistent with the general conception of the principle of the determining dispatch station (DDS) in the nervous system integration activity. These results reveal that the appearance of the DDS induces secondary excitation foci which fully reproduce tha work regimen of the DDS. Switching of such "mirror" foci representing "the destination stations" from the DDS influence led to the elimination of the activity induced in them.     

Motor simulation without motor expertise: enhanced corticospinal excitability in visually experienced dance spectators

The human "mirror-system" is suggested to play a crucial role in action observation and execution, and is characterized by activity in the premotor and parietal cortices during the passive observation of movements. The previous motor experience of the observer has been shown to enhance the activity in this network. Yet visual experience could also have a determinant influence when watching more complex actions, as in dance performances. Here we tested the impact visual experience has on motor simulation when watching dance, by measuring changes in corticospinal excitability. We also tested the effects of empathic abilities. To fully match the participants' long-term visual experience with the present experimental setting, we used three live solo dance performances: ballet, Indian dance, and non-dance. Participants were either frequent dance spectators of ballet or Indian dance, or "novices" who never watched dance. None of the spectators had been physically trained in these dance styles. Transcranial magnetic stimulation was used to measure corticospinal excitability by means of motor-evoked potentials (MEPs) in both the hand and the arm, because the hand is specifically used in Indian dance and the arm is frequently engaged in ballet dance movements. We observed that frequent ballet spectators showed larger MEP amplitudes in the arm muscles when watching ballet compared to when they watched other performances. We also found that the higher Indian dance spectators scored on the fantasy subscale of the Interpersonal Reactivity Index, the larger their MEPs were in the arms when watching Indian dance. Our results show that even without physical training, corticospinal excitability can be enhanced as a function of either visual experience or the tendency to imaginatively transpose oneself into fictional characters. We suggest that spectators covertly simulate the movements for which they have acquired visual experience, and that empathic abilities heighten motor resonance during dance observation.     

On the mechanisms of stimulation and inhibition during germination of wheat seeds in extremely low frequency electromagnetic fields

It has been shown that the effects of stimulation of germination of wheat seeds by electromagnetic field depend on the degree of membrane tension during imbibition of seeds in sucrose solutions. This provides further confirmation of the influence of electromagnetic fields on the release of proteins from the bound state on the membranes. The prolonged treatment with electromagnetic fields during the imbibition of seeds leads not only to the inhibition of germination of sprouts but also to a decrease in their germinability, which can be as strong as twofold for seeds with the initial low germinability. This is related to the desynchronization of germination processes, caused by the stimulation of the release of proteins and inhibition of another stage during the cell division, the assembly of complex structures. It is noted that the activation of the release of proteins and inhibition of their binding by the action of electromagnetic fields must elevate the cell excitability. The presumably, the excitability of cells determines the effects of magnetic storms and high solar activity on the physiological state of organisms.     

Changes in the electrical properties of atrial trabecula induced by an electric stimulus]

Electrical activity, excitation threshold and "steady--state" current-voltage, relationship (estimated under voltage clamp conditions) in the membrane of chicken embryo atrial trabecula were investigated by means of double succrose-gap technique. Application of short (10 msec) electrical stimuli with magnitudes up to 6.10(-5) a (1-150 threshold) resulted in increased excitability and appearance of spontaneous activity. Release of neurotransmitters and polarity of the applied sitmulus are shown not to play a significant role in the changes in membrane excitability observed, the main cause of the latter being the increased sodium permeability of the membrane.     

Effect of diphenylhydantion on cortical epileptogenic foci in the rat

In acute experiments we studied the effect of diphenylhydantoin (DPH, 60 mg/kg i.p.) on the activity of cortical penicillin foci in 81 male rats. DPH reduced the discharge frequencies (measured by means of histograms of the intervals between adjacent discharges) and limited the projection of the discharges into non-primary cortical areas. The results for the administration of DPH before formation and after stabilization of the focus were qualitatively the same. DPH statistically significantly slowed down synchronization of the activity of two symmetrical cortical foci, but did not affect the progress of the synchronization of two asymmetrical foci, which was also very slow in the controls. DPH did not inhibit the possibility of triggering focal discharges by peripheral nerve stimulation. A detailed evaluation of focal activity allows the anti-epileptic effect of DPH to be demonstrated even in a model as potent as the penicillin focus in animals without general anaesthesia.     

On the possible role of focal cooling of the heart in the mechanism of repetitive ventricular extra beats

The role of myocardial foci in the mechanism of ventricular arrhythmias was studied by local cooling of the intact dog heart. At normal heart rate conduction delay in the focus is not sufficient to account for re-entry of impulses. However, a premature stimulus applied near the refractory period caused sudden prolongation of conduction giving rise to nonstimulated extra beats, arising probably as a result of re-entry. The phenomenon is presumably due to the fact that at this time a large portion of the fibres has not yet recovered excitability. With increasing size of the focus, there is increased asynchrony of recovery of excitability and premature stimuli falling later in the cycle are able to produce reentry. A negative correlation exists between cycle length and conduction delay and a positive correlation between cycle length and the coupling interval, i.e. the time interval between a premature stimulus and the first nonstimulated extra beat.     

Decreased acetylcholinesterase activity in the area of epileptogenic foci created by met-enkephalin in the hippocampus of rats

Experiments on rats with electrochemotrodes implanted in the left and right hippocamp have shown that in epileptogenic foci created by microinjections of met-enkephalin or D-ala-2-met-enkephalin into the hippocamp, acetylcholinesterase activity (AChE) was diminished. It is assumed that reduction in AChE activity is an adaptive mechanism by which the excitability of hippocampal inhibitory basket cells, which are sensitive to acetylcholine, is increased.     

Modelling psychosis in cats by creating a generator of pathologically enhanced excitation in one of the septal nuclei

The experiments on adult freely behaving cats have shown that the injection of penicillin into the internal part (TI) of bed nucleus of stria terminalis (BST) caused the formation of the generator of pathologically enhanced excitation (GPEE). This part of BST became hyperactive and played the role of a pathologic determinant which caused the formation of a complex pathologic system and behavioural disorders with catatonia, stereotypy, food rejection, eating of uneatable things, hypoalgesia, zoosocial behavioural changes, depression of different emotions, etc. The development of these disorders was progressing and was accompanied by corresponding electrophysiological activity in TI and other brain structures studied. Coagulation of GPEE zone at the early stages of the process prevented the development of the above disorders.     

Function of the superior colliculi of the corpora quadrigemina during creation of a local focus of increased excitability in the mesencephalic reticular formation and sensomotor cortex

In chronic experiments on waking rabbits, the foci of heightened excitability in the sensorimotor cortex and mesencephalic reticular formation affected in a similar way the background neuronal activity in the superior colliculi and that evoked by light stimuli. The effect was manifested in elimination of inhibitory pauses in the neuronal response to light stimulus and in a general increase of discharge frequency. Similarity of the cortical and reticular influences is due to their possible mediation by the same collicular interneurones participating in inhibitory pauses formation in the process of backward inhibition. Increased neuronal activity in the superior colliculi under the action of local foci in the sensorimotor cortex and mesencephalic reticular formation correlated with appearance of forelimb motor reaction to isolated light stimulus testifying to a formation of a functional connection between the visual and motor analyzers. Possible role of the superior colliculi in this process and their participation in the formation of a visually controlled reaction is discussed.     

Contralateral input modulates the excitability of dorsal horn neurons involved in noxious signal processes. Potential role in neuronal sensitization

Wide Dynamic Range (WDR) neurons in the spinal cord receive inputs from the contralateral side that, under normal conditions, are ineffective in generating an active response. These inputs are effective when the target WDRs change their excitability conditions. To further reveal the mechanisms supporting this effectiveness shift, we investigated the weight of the excitation of the contralateral neurons on the target WDR responses. In the circuit of presynaptic (sending) and postsynaptic (receiving) neurons in crossed spinal connections the fibres that form the presynaptic neurons impinge on postsynaptic neurons can be considered the final relay of this contralateral pathway. The enhancement of the presynaptic neuron excitability may thus modify the efficacy of the contralateral input. Pairs of neurons each on a side of the spinal cord, at the L5-L6 lumbar level were simultaneously recorded in intact, anaesthetized, paralysed rats. The excitatory aminoacid NMDA and strychnine, the antagonist of the inhibitory aminoacid glycine, were iontophoretically administrated to presynaptic neurons to increase their excitability. Before and during the drug administration, spontaneous and noxious-evoked activities of the neurons were analysed. During the iontophoresis of the two substances we found that noxious stimuli applied to the receptive field of presynaptic neurons activated up to 50% of the previously unresponsive postsynaptic neurons on the opposite side. Furthermore, the neurons on both sides of the spinal cord showed significantly increased spontaneous activity and amplified responses to ipsilateral noxious stimulation. These findings indicate that the contralateral input participates in the circuit dynamics of spinal nociceptive transmission, by modulating the excitability of the postsynaptic neurons. A possible functional role of such a nociceptive transmission circuit in neuronal sensitization following unilateral nerve injury is hypothesized.     

Contralateral input modulates the excitability of dorsal horn neurons involved in noxious signal processes. Potential role in neuronal sensitization

Wide Dynamic Range (WDR) neurons in the spinal cord receive inputs from the contralateral side that, under normal conditions, are ineffective in generating an active response. These inputs are effective when the target WDRs change their excitability conditions. To further reveal the mechanisms supporting this effectiveness shift, we investigated the weight of the excitation of the contralateral neurons on the target WDR responses. In the circuit of presynaptic (sending) and postsynaptic (receiving) neurons in crossed spinal connections the fibres that form the presynaptic neurons impinge on postsynaptic neurons can be considered the final relay of this contralateral pathway. The enhancement of the presynaptic neuron excitability may thus modify the efficacy of the contralateral input. Pairs of neurons each on a side of the spinal cord, at the L5–L6 lumbar level were simultaneously recorded in intact, anaesthetized, paralysed rats. The excitatory aminoacid NMDA and strychnine, the antagonist of the inhibitory aminoacid glycine, were iontophoretically administrated to presynaptic neurons to increase their excitability. Before and during the drug administration, spontaneous and noxious-evoked activities of the neurons were analysed. During the iontophoresis of the two substances we found that noxious stimuli applied to the receptive field of presynaptic neurons activated up to 50% of the previously unresponsive postsynaptic neurons on the opposite side. Furthermore, the neurons on both sides of the spinal cord showed significantly increased spontaneous activity and amplified responses to ipsilateral noxious stimulation. These findings indicate that the contralateral input participates in the circuit dynamics of spinal nociceptive transmission, by modulating the excitability of the postsynaptic neurons. A possible functional role of such a nociceptive transmission circuit in neuronal sensitization following unilateral nerve injury is hypothesized.     

The mechanism of interaction between the thalamic posterior lateral nucleus and the sensomotor cortex in rabbits

The thalamic posterior lateral nucleus was shown to exert phasic and tonic effects on the function of sensomotor cortex: the former in the form of pulvinar-cortical responses, and the latter in the form of foci of increased or decreased excitability. The findings suggest an inhibitory tonic effect of the sensomotor cortex on neuronal network of the posterior lateral nucleus.