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.     

Changes in the activity of gamma-amino butyric acid transaminase and succinic semialdehyde dehydrogenase in the cobalt and iron experimental epileptogenic foci in the rat brain

GABA-transaminase (GABA-T) and succinic semialdehyde dehydrogenase (SSA-DH) activities were measured in the mitochondrial fractions from the cobalt- and FeCl3-induced chronic epileptogenic foci in the rat brain. Electroencephalographically, the FeCl3 epileptogenic focus remained active for a duration longer than that of the cobalt focus. In both the foci SSA-DH activity showed significant increases which were concomitant with the EEG epileptiform activity. In cobalt focus, the GABA-T activity fell whereas, in the FeCl3 focus it was unchanged. In cobalt focus fall in GABA-T activity seemed to be concomitant with EEG epileptiform discharge. The measurements of the enzyme activities in the mirror (secondary) foci showed that, except for a brief stimulation of SSA-DH activity in the mirror focus in FeCl3 epileptic animals, the enzyme activities remained unchanged. Possible significance of the observed enzymatic changes in the physiology of epileptogenic focus is discussed.     

Histone alteration in the nuclei of different types of neurons in a "mirror" epileptiform focus in rat brain]

Total histones estimated after M. Alfred and I. Geschwind were studied cytophotometrically in nuclei of neurons of different types (layers III and V in the frontal-parietal cortex and in the thalamic lateral nucleus) of the "mirror" epileptiform focus in the rat brain on the 11th and 63d day after cobalt implantation. On the 11th day of the experiment, integral optic density of the histones decreased by 33%, 25% and 37%, and the area of the nuclei -- by 27%, 24% and 35% in the neurons of layers II and V in the frontal-parietal cortex and in the thalamic lateral neucleus, respectively. On the 63d, integral optic density of the histones in the neurons mentioned increased respectively by 42%, 52% and 42%, and the area of the nuclei -- by 21%, 43% and 27%. Concentration of the histones in the nuclei decreased by 3--9% on the 11th day and increased, except layer V, by 9--18% on the 63d of the experiment. Interconnection between changes in histone content and total proteins in cytoplasm of functionally different neurons in the "mirror" epileptiform focus is disscussed, with special reference to histones as a regular of genetic activity for protein synthesis.     

The subjective auditory space of epileptic patients with lesions in both the temporal cortical area and the hippocampus

Parameters of the subjective auditory space formed under the conditions of dichotic stimulation during movement of the acoustic image in different directions were studied in 13 epileptic patients with lesions in both the temporal cortex and the hippocampus. The pattern and degree of the movement trajectory of the subjective acoustic image (SAI) were determined in two groups of patients (in seven patients with the right-side focus and six patients with the left-side focus of convulsive activity, depending on the direction of moving and the initial interauricular delay (700, 400, and 200 μs)). A significant decrease in the SAI movement trajectory was observed in patients with right-or the left-side lesions in the temporal cortex and hippocampus as compared to healthy subjects or patients with temporal cortical epilepsy in the cases when the SAI movement stopped at the side of the epileptic focus. The analysis of the parameters of the SAI movement in each hemisphere showed a highly significant difference between the movement trajectories for all values of initial delays as compared to the control group of healthy subjects (p < 0.01) and patients with a relatively isolated lesion of the right temporal cortex (p < 0.05). A significant role of the epileptic lesion of the hippocampus (which is not an auditory structure) in the impairment of spatial hearing was demonstrated. The characteristics of the functional asymmetry because of simultaneous epileptic lesion of the temporal cortex and hippocampus, which led to the impairment of the binaural effect, are discussed.     

Evidence for an ascending inhibitory histaminergic pathway to the cerebral cortex.

Previous observations from our laboratory indicate that metiamide is a specific histamine antagonist in rat cerebral cortex. In view of the recent finding that histamine levels and L-histidine decarboxylase (EC 4.1.1.22) activity in cerebral cortex decrease following disruption of the ipsilateral medial forebrain bundle (MFB), the present investigation was undertaken to examine whether iontophoretically applied metiamide antagonizes the inhibition of deep cerebral cortical neurones produced by stimulation of the MFB. In rats anaesthetized with a mixture of methoxyflurane, nitrous oxide and oxygen, stimulation of the ipsilateral MFB or the cortical surface with iontophoretically applied histamine depressed the firing of cortical neurones. Metiamide antagonized the histamine-induced depression and reduced the duration of inhibition produced by MFB stimulation. However, it did not alter the inhibition induced by the cortical surface stimulation. These results indicate that a histaminergic pathway ascending through the MFB may inhibit rat cerebral cortical neurones.     

Tyrosinated alpha-tubulin changes following epileptogenic and non-epileptogenic lesions in rat brain cortex

The expression of the tyrosinated isoform of alpha-tubulin was monitored in rat frontal cortex, in order to investigate the neuronal plasticity changes occurring either in a mirror focus or in a deafferented area. A mirror focus was triggered by epidural implantation of a cobalt gelatin disk in the contralateral left somatosensory area (group one). A deafferented area was obtained by surgical removal of the left frontal cortex (group two). All animals including controls underwent EcoG recordings immediately before killing (45, 60, 90 days post surgery). The right frontal cortex was removed from all the animals and processed with Western blot method. EcoG recordings revealed a paroxysmal activity in epileptic rats, whereas in rats with frontal deafferentation and controls, EcoG activity was normal. A significant increase in tyrosinated alpha-tubulin expression was detected both in the mirror focus (group one) and the "non-epileptic" deafferented frontal cortex (group two) in comparison with controls (group three). The transcallosal deafferentation, which is involved in both epileptogenic and non-epileptogenic lesions, is supposed to play a role in the mechanism responsible for the plasticity responses recorded in the cortical areas studied.     

Electroencephalographic study of iron-induced chronic focal cortical epilepsy in rat: propagation of cortical epileptic activity to substantia nigra and thalamus.

Cortical epileptic focus was produced by an intracortical injection of FeCl3 in rat cerebral cortex using standard techniques. How after its onset in the cortical focus, the epileptiform activity evolved with time in the thalamus and substantia nigra has been determined. To study the propagation of the epileptiform activity, the local EEG and multiple unit action potentials were recorded from these structures simultaneously with the cortical epileptiform EEG. The results showed that in thalamus and substantia nigra epileptiform activity appeared simultaneously with that in the cortical focus. Intensity of epileptic activity in thalamus and substantia nigra on the whole increased in parallel with that in the cortical focus. The results suggest that the thalamic and nigral epileptiform activity may reinforce the cortical epileptiform activity.     

Effect of diazepam on the Na, K-ATPase state in a penicillin--induced hyperactivity focus in the cerebral cortex]

Intramuscular injection of diazepam to rats at doses of 0.01 and 2 mg/kg 25-30 min after penicillin application to the rat brain cortex leads to alteration of periodic appearance of epileptic seizures (ES), to changes in the seizure pattern, and to emergence of periodic acceleration of epileptiform discharges (ED). Injection of diazepam at a dose of 2 mg/kg 20 min before penicillin application results in the reduction of ED latency in the epileptogenic focus and in a decrease in their frequency before seizures as compared to the control animals without diazepam injection. ES appear irregularly, their quantity is markedly reduced while duration is increased. Diazepam injection leads to disappearance of the rat moving reaction during ER and ES. In vivo experiments diazepam (2 mg/kg) does not influence brain cortex Na, K-ATPase of crude synaptosomes. However, diazepam leads to an increase in Na, K-ATPase activity both in the primary and dependent secondary epileptogenic foci. It is suggested that the anticonvulsant action of diazepam may be underlain by its activating effect on Na, K-ATPase of neuronal membranes in the epileptogenic focus.     

Electrographic Waveform Structure Predicts Laminar Focus Location in a Model of Temporal Lobe Seizures In Vitro

Temporal lobe epilepsy is the most common form of partial-onset epilepsy and accounts for the majority of adult epilepsy cases in most countries. A critical role for the hippocampus (and to some extent amygdala) in the pathology of these epilepsies is clear, with selective removal of these regions almost as effective as temporal lobectomy in reducing subsequent seizure risk. However, there is debate about whether hippocampus is ‘victim’ or ‘perpetrator’: The structure is ideally placed to ‘broadcast’ epileptiform activity to a great many other brain regions, but removal often leaves epileptiform events still occurring in cortex, particularly in adjacent areas, and recruitment of the hippocampus into seizure-like activity has been shown to be difficult in clinically-relevant models. Using a very simple model of acute epileptiform activity with known, single primary pathology (GABA_A Receptor partial blockade), we track the onset and propagation of epileptiform events in hippocampus, parahippocampal areas and neocortex. In this model the hippocampus acts as a potential seizure focus for the majority of observed events. Events with hippocampal focus were far more readily propagated throughout parahippocampal areas and into neocortex than vice versa. The electrographic signature of events of hippocampal origin was significantly different to those of primary neocortical origin – a consequence of differential laminar activation. These data confirm the critical role of the hippocampus in epileptiform activity generation in the temporal lobe and suggest the morphology of non-invasive electrical recording of neocortical interictal events may be useful in confirming this role.     

The anticonvulsive effect of non-NMDA antagonist GYKI 52466 on 3-aminopyridine-induced primary and secondary cortical ictal activity in rat

The effect of GYKI 52466, a selective, non-competitive antagonist of the AMPA glutamate receptor subtype was investigated on the development, expression and propagation of 3-aminopyridine-induced cortical ictal activity, both in the primary and secondary focus. In one group of animals GYKI 52466 was administered intraperitoneally, 20 minutes prior to the local application of the convulsant the surface of the cortex of anaesthetized rats. Control animals were injected by physiological solution. Different parameters of electrographic ictal discharges were measured under the influence of the antagonist and compared to control values. The results demonstrate that GYKI 52466 exerts anticonvulsive effects on both the induction and the expression of primary and secondary electrical ictal activity, by delaying the onset of the first ictal period, shortening the duration of ictal activity and decreasing the amplitudes of epileptiform discharges. However, the seizure propagation was not influenced significantly. It is suggested that the initiation, maintenance and the propagation of spontaneous seizures may be controlled by separate mechanisms and that changes can occur in one of the procedures without parallel changes in others. The observations of the present study extend those reported previously by others, namely that activation of non-NMDA receptors is significantly involved in the initiation and maintenance of cortical epileptiform activity.     

Unilateral epilepsy and the asymmetry of postepileptic sleep

In the paper the analysis is given of "penicillin" epilepsy in animals (cats) in conditions of different forms of deafferentation of one of the halves of the fore brain. It is shown, that in conditions of combined section of one half of the operculum of the midbrain and commissural systems of the endbrain, diencephalon and midbrain, under large doses of penicillin, unilateral convulsive activity is recorded in summate electrical activity of one of the brain halves at the side of the midbrain lesion. After the completion of unilateral organization of the epileptic process an asymmetrical sleep takes place: at the side, at which epileptiform activity was recorded, a more deep phase of the sleep appears than in the opposite brain half.     

Time courses of aspartate and glutamate concentrations in the focus area during penicillin induced epileptiform activity in awake rats

1. In 16 awake rats, the time courses of cortical aspartate (ASP) and glutamate (GLU) concentrations were investigated before, during and after penicillin-induced epileptiform activity (PCN-EA). The amino acids were collected by means of the microdialysis technique from a site within the motor cortex located close to the PCN focus. PCN-EA was recorded by means of 12 cortical electrodes. 2. The median time courses of ASP and GLU concentrations demonstrated no relation to the time course of PCN-EA. In contrast, the analysis of individual time courses revealed three response types for both ASP and GLU which could not be related to specific sites within the motor cortex. 3. The ASP concentration was i) not affected by epileptiform activity (8 of 16 rats), ii) changed synchronously with the PCN-EA (3 of 16), or iii) increased transiently or in a long-lasting manner during or after disappearance of PCN-EA (5 of 16). 4. The GLU concentration was i) not effected or only slightly affected by epileptiform activity (5 of 16), ii) decreased strongly during the activity (7 of 16), or iii) increased during the epileptiform activity (4 of 16). 5. If all rats were taken into account, the overall observation was absence of a uniform correlation type between the time courses of ASP and GLU concentrations; i.e. epileptiform activity affects the time courses of ASP and GLU concentrations in an independent manner. 6. These results demonstrate that consideration of median values alone can mask significant effects of epileptiform activity on the biochemistry of the brain in individual animals. The study also shows that a consideration of individual time courses of physiological and biochemical parameters is mandatory for the understanding of basic mechanisms of epilepsy. The results support the hypothesis about the activation of neuroprotective mechanisms by epileptiform activity.     

In vivo optical mapping of epileptic foci and surround inhibition in ferret cerebral cortex

The population of neurons participating in an epileptiform event varies from moment to moment. Most techniques currently used to localize epileptiform events in vivo have spatial and/or temporal sampling limitations. Here we show in an animal model that optical imaging based on intrinsic signals is an excellent method for in vivo mapping of clinically relevant epileptiform events, such as interictal spikes, ictal onsets, ictal spread and secondary homotopic foci. In addition, a decrease in the optical signal correlates spatially with a decrease in neuronal activity recorded from cortex surrounding an epileptic focus. Optical mapping of epilepsy might be a useful adjunct in the surgical treatment of neocortical epilepsy, which critically depends on the precise localization of intrinsically epileptogenic neurons.     

Synchronization of electrical field potentials in neocortex of rat after isolation of a cortex island in the contralateral brain hemisphere

A correlation between the number of boutons and synchronization of electrical activity in two sites of the intact right somatosensory cortex of rats was anakyzed at different stages of axonal sprouting elicited by isolation of a cortex slab in the left cortex. Time delay between the development of epileptiform field potentials in two sites of intact cortex located at a distance of 4 mm from each other was determined as a parameter of synchronization. The analysis was carried out in 30 and 90 days after the complete isolation of the neural island in a symmetrical site of the contralateral cortex. Epileptiform activity was induced by penicillin. A significant increase in the number of boutons in the II and V layers of the intact cortex observed 90 days after the isolation of neural island in a symmetrical site of the cortex corresponded to a significant decrease in the delay of electrical activity development. Similar effects were observed in the V layer of the island 30 days after the isolation. The results suggest that the cortex lesion activates formation of new synaptic boutons in a contralateral site and increases a degree of synchronization of electrical activity, which may affect the epileptogenesis. The data suggest that pyramids of the III and, most probably, V layers form a neuronal network in the rat neocortex thus providing synchronization of epileptiform field potentials.     

Mechanisms of epileptogenic effects of some convulsants on the neuronal activity in the neocortex

The data obtained in the studies of neurophysiological aspects of epileptogenesis in the brain cortex, which have been carried out in our laboratory for many years, are used for the analysis of epileptogenic effects of a few convulsants (penicillin, strychnine, and d-tubocurarine) on the activity of neocortical neurons. It has been demonstrated that the development of the epileptiform activity in the cortex is accompanied by suppression of IPSP, and the above convulsants directly influence the mechanisms of postsynaptic inhibition. Epileptogenic effects of strychine and penicillin are based on blocking of chloride ion channels and depend on the direction of chloride currents. The role of excitatory and inhibitory synaptic interactions among neurons in generation of the epileptiform activity is discussed.     

Effect of local depression of inhibition on intercentral relations in the rat spinal cord

Changes in spinal reflexes of rats were studied after the formation of local depression of inhibition (a "determining dispatch station" of paroxysmal activity), generating an increased excitation wave, by means of tetanus toxin. Tonic and rhythmic paroxysmal activity generated in the poisoned half of the lumbar segments was shown to evoke discharges of all spinal and bulbar motoneurons with certain temporal characteristics. Depression of unit activity in the focus with glycine abolished this phenomenon. Excitation of the focus created on one side of the cervical segments evoked a pathologically increased scratch reflex of the ipsilateral hind limb, unconnected with a disturbance of inhibition of lumbar motoneurons. The focus had enhanced excitatory and inhibitory effects on monosynaptic reflexes of lumbar flexor motoneurons. The role of local depression of inhibition in the function of the nervous system is discussed.     

Asymmetric activation of the primary motor cortex during observation of a mirror reflection of a hand

Mirror therapy is an effective technique for pain relief and motor function recovery. It has been demonstrated that magnetic 20-Hz activity is induced in the primary motor cortex (M1) after median nerve stimulation and that the amount of the stimulus-induced 20-Hz activity is decreased when the M1 is activated. In the present study, we investigated how the image or the mirror reflection of a hand holding a pencil modulates the stimulus-induced 20-Hz activity in the M1. Neuromagnetic brain activity was recorded from 13 healthy right-handed subjects while they were either viewing directly their hand holding a pencil or viewing a mirror reflection of their hand holding a pencil. The 20-Hz activity in the left or the right M1 was examined after the right or the left median nerve stimulation, respectively, and the suppression of the stimulus-induced 20-Hz in the M1 by viewing directly one hand holding a pencil or by viewing the mirror image of the hand holding a pencil was assumed to indicate the activation of the M1. The results indicated that the M1 innervating the dominant hand was suppressed either by viewing directly the dominant hand holding a pencil or by viewing the mirror image of the non-dominant hand holding a pencil. On the other hand, the M1 innervating the non-dominant hand was activated by viewing the mirror image of the dominant hand holding a pencil, but was not activated by viewing directly the non-dominant hand holding a pencil. The M1 innervating either the dominant or the non-dominant hand, however, was not activated by viewing the hand on the side ipsilateral to the M1 examined or the mirror image of the hand on the side contralateral to the M1 exaimined. Such activation of the M1 might induce some therapeutic effects of mirror therapy.     

Effect of diazepam on cyclic change of excitability in a cortical epileptic focus

On application of penicillin solution to the motor cortex of rats and electrical stimulation of the ventroposterolateral thalamic nucleus (VPL) with a frequency of 1/sec and with a strength three times greater than the threshold for the primary evoked potential, alternation of "active" and "passive" neurons was observed in the zone of the epileptic focus. "Active" neurons were characterized by the regular appearance of epileptiform discharges in response to each stimulation of VPL. In the course of the "passive" periods stimulation of VPL led only to the appearance of primary evoked potentials. Diazepam in a dose of 2 mg/kg completely disturbed spike generation in the epleptic focus, but in a dose of 0.1 mg/kg it caused disturbance of the established cyclic change of excitability in the focus, which was restored after stimulation with a frequency of 2/sec.Institute of General Pathology and Pathological Physiology, Academy of Medical Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 12, No. 6, pp. 563–570, November–December, 1980.     

Motor learning in man: A review of functional and clinical studies

This chapter reviews results of clinical and functional imaging studies which investigated the time-course of cortical and subcortical activation during the acquisition of motor a skill. During the early phases of learning by trial and error, activation in prefrontal areas, especially in the dorsolateral prefrontal cortex, is has been reported. The role of these areas is presumably related to explicit working memory and the establishment of a novel association between visual cues and motor commands. Furthermore, motor associated areas of the right hemisphere and distributed cerebellar areas reveal strong activation during the early motor learning. Activation in superior-posterior parietal cortex presumably arises from visuospatial processes, while sensory feedback is coded in the anterior-inferior parietal cortex and the neocerebellar structures. With practice, motor associated areas of the left-hemisphere reveal increased activity. This shift to the left hemisphere has been observed regardless of the hand used during training, indicating a left-hemispheric dominance in the storage of visuomotor skills. Concerning frontal areas, learned actions of sequential character are represented in the caudal part of the supplementary motor area (SMA proper), whereas the lateral premotor cortex appears to be responsible for the coding of the association between visuo-spatial information and motor commands. Functional imaging studies which investigated the activation patterns of motor learning under implicit conditions identified for the first, a motor circuit which includes lateral premotor cortex and SMA proper of the left hemisphere and primary motor cortex, for the second, a cognitive loop which consists of basal ganglia structures of the right hemisphere. Finally, activity patterns of intermanual transfer are discussed. After right-handed training, activity in motor associated areas maintains during performance of the mirror version, but is increased during the performance of the original-oriented version with the left hand. In contrary, increased activity during the mirror reversed action, but not during the original-oriented performance of the untrained right hand is observed after left-handed training. These results indicate the transfer of acquired right-handed information which reflects the mirror symmetry of the body, whereas spatial information is mainly transferred after left-handed training. Taken together, a combined approach of clinical lesion studies and functional imaging is a promising tool for identifying the cerebral regions involved in the process of motor learning and provides insight into the mechanisms underlying the generalisation of actions.     

Character of neuronal functional associations according to the content of RNA and SH-groups in the cat cerebral cortex]

A new principle of taxonomy was used for determination of the spaceal character of the neuron cortex associations based on RNA and SH-group contents. The experiments were performed on the intact cat's somatosensory cortex, and after epileptiform activity induced by electrical stimulation. In the intact cortex, the neuronal mosaic of metabolic activity (determined by RNA and SH-group contents) was meshed, whereas in the hemisphere with epileptiform activity this mosaic was formed by less numerous but larger groups of cells. The functional significance of these groups is discussed.