Stimulation of the hippocampus and its effect on electrographic manifestations of the brain in unrestrained rats.

The dorsal hippocampus was electrically stimulated in unanaesthetized, unrestrained rats with a cobalt-gelatin rod in their cortex. The significance of the hippocampus in the elicitation of both physiological spontaneous rhythmic activity (episodic activity of 8--9/sec frequency bound, in rats, to a state of quiet wakefulness, and "sleep spindles") and pathological rhythmic activity of the self-sustained after-discharge (SSAD) type was determined from the aspect of the EEG and behavioural characteristics. 1. Single electrical pulses (0.1 msec, 1--10 V, 0.3/sec) elicited an evoked potential bilaterally in the somatosensory cortex. Elicitation of rhythmic after-activity (of the type of episodes or sleep spindles) was observed only in some cases in which an adequately strong stimulus was used. 2. Repeated series of rhythmic electrical stimuli following each other at short intervals (2--3 min) led to the formation of SSAD in about one third of the cases and at all stimulation frequencies (3-15/sec), although low frequencies (3--4/sec) were the least effective. The character of the SSAD and simultaneous behavioural phenomena differed fundamentally from those evoked by electrical stimulation of the thalamus (Chocholová et al. 1977). The development of paroxysmal after-activity was signalled by responses of a more or less distinct "recruiting" character during stimulation. On the basis of a comparison of electrographic and behavioural manifestations after electrical stimulation of the thalamus and hippocampus, the possibility of both thalamic and extrathalamic projection from the hippocampus to the cortical region is considered.     

The relationship between vigilance and cortical EEG manifestations after electrical stimulation of the thalamus and hippocampus in unrestrained rats.

The thalamus or hippocampus of unanaesthetized rats with impaired cortical and subcortical electrodes was stimulated with rhythmic series of electrical pulses of 3--15/sec frequency. In both cases, stimulation either did not affect vigilance, or led to a higher degree of wakefulness. The incidence of recruiting responses (RR) and of self-sustained afterdischarges (SSAD) evoked by stimulation of the thalamus was not correlated to the preceding state of vigilance. In stimulation of the hippocampus, a significantly higher incidence of SSAD was found in the quiet waking state. The correlation between the elicitation of RR and SSAD was also significantly the highest after stimulation of the hippocampus during wakefulness.     

Rhythmic metrazol activity and cortical spreading depression

The incidence of segments of rhythmic metrazol activity (RMA) in cortical leads and in the thalamus and hippocampus was studied in acute experiments on nine male albino laboratory rats. First of all we studied activity after administering metrazol in an i.p. dose of 50 mg/kg, without any further treatment, and then, after a control recording, we induced cortical spreading depression and observed its effect on the incidence and synchronization of RMA in the individual leads. We came to the conclusion that the thalamus is incapable of isolated production of RMA. The cortex is able to produce RMA without participation by the studied structures of the specific thalamus and hippocampus; RMA probably originates in the cortex itself. Generalization is impaired, but not eliminated, by a cortical block. The hippocampus independently produces another type of rhythmic activity.     

Attenuation of High-Frequency (50-200 Hz) Thalamocortical EEG Rhythms by Propofol in Rats Is More Pronounced for the Thalamus than for the Cortex

Background

Thalamocortical EEG rhythms in gamma (30-80 Hz) and high-gamma (80-200 Hz) ranges have been linked to arousal and conscious processes. To test the hypothesis that general anesthetics attenuate these rhythms, we characterized the concentration-effect relationship of propofol on the spectral power of these rhythms. In view of the ongoing debate about cortex versus thalamus as the primary site of anesthetic action for unconsciousness, we also compared the relative sensitivity of cortex and thalamus to this effect propofol.

Methods

Adult male Long-Evans rats were chronically implanted with electrodes in somatosensory (barrel) cortex and ventroposteromedial thalamus. Propofol was delivered by a computer-controlled infusion using real-time pharmacokinetic modeling to obtain the desired plasma concentration. Spectral power was assessed during baseline, at four stable propofol plasma-concentrations (0, 3,6,9,12 μg/ml) and during recovery over four frequency ranges (30-50, 51-75, 76-125, 126-200 Hz). Unconsciousness was defined as complete loss of righting reflex. Multiple regression was used to model the change of power (after logarithmic transformation) as a function of propofol concentration and recording site.

Results

Unconsciousness occurred at the 9 μg/ml concentration in all animals. Propofol caused a robust linear concentration-dependent attenuation of cortical power in the 76-200 Hz range and of thalamic power in the 51-200 Hz range. In all instances the concentration-effect slope for the thalamus was markedly steeper than for the cortex. Furthermore the lowest concentration causing unconsciousness significantly reduced cortical power in the 126-200 Hz range and thalamic power in the 51-200 Hz range.

Conclusions

Propofol causes a concentration-dependent attenuation of the power of thalamocortical rhythms in the 51-200 Hz range and this effect is far more pronounced for the thalamus, where the attenuation provides a robust correlate of the hypnotic action of propofol.     

Correlation of spike intervals and amplitudes in hypersynchronous EEG episodes in rat with cobalt focus.

EEG activity was recorded from rats with chronic cobalt foci and implanted electrodes. Within this activity, hypersynchronous rhythmic spike episodes (and those of waves) of mean frequency of 8-9/sec were studied. The spike amplitude-interval relationship was assessed, using correlation analysis method. A positive correlation of an exponential nature was found to be growing in line with temporal development of episode.     

Unilateral and Bilateral Cortical Resection: Effects on Spike-Wave Discharges in a Genetic Absence Epilepsy Model

Research Question

Recent discoveries have challenged the traditional view that the thalamus is the primary source driving spike-and-wave discharges (SWDs). At odds, SWDs in genetic absence models have a cortical focal origin in the deep layers of the perioral region of the somatosensory cortex. The present study examines the effect of unilateral and bilateral surgical resection of the assumed focal cortical region on the occurrence of SWDs in anesthetized WAG/Rij rats, a well described and validated genetic absence model.

Methods

Male WAG/Rij rats were used: 9 in the resected and 6 in the control group. EEG recordings were made before and after craniectomy, after unilateral and after bilateral removal of the focal region.

Results

SWDs decreased after unilateral cortical resection, while SWDs were no longer noticed after bilateral resection. This was also the case when the resected areas were restricted to layers I-IV with layers V and VI intact.

Conclusions

These results suggest that SWDs are completely abolished after bilateral removal of the focal region, most likely by interference with an intracortical columnar circuit. The evidence suggests that absence epilepsy is a network type of epilepsy since interference with only the local cortical network abolishes all seizures.     

Neuronal Networks during Burst Suppression as Revealed by Source Analysis

Introduction

Burst-suppression (BS) is an electroencephalography (EEG) pattern consisting of alternant periods of slow waves of high amplitude (burst) and periods of so called flat EEG (suppression). It is generally associated with coma of various etiologies (hypoxia, drug-related intoxication, hypothermia, and childhood encephalopathies, but also anesthesia). Animal studies suggest that both the cortex and the thalamus are involved in the generation of BS. However, very little is known about mechanisms of BS in humans. The aim of this study was to identify the neuronal network underlying both burst and suppression phases using source reconstruction and analysis of functional and effective connectivity in EEG.

Material/Methods

Dynamic imaging of coherent sources (DICS) was applied to EEG segments of 13 neonates and infants with burst and suppression EEG pattern. The brain area with the strongest power in the analyzed frequency (1–4 Hz) range was defined as the reference region. DICS was used to compute the coherence between this reference region and the entire brain. The renormalized partial directed coherence (RPDC) was used to describe the informational flow between the identified sources.

Results/Conclusion

Delta activity during the burst phases was associated with coherent sources in the thalamus and brainstem as well as bilateral sources in cortical regions mainly frontal and parietal, whereas suppression phases were associated with coherent sources only in cortical regions. Results of the RPDC analyses showed an upwards informational flow from the brainstem towards the thalamus and from the thalamus to cortical regions, which was absent during the suppression phases. These findings may support the theory that a “cortical deafferentiation” between the cortex and sub-cortical structures exists especially in suppression phases compared to burst phases in burst suppression EEGs. Such a deafferentiation may play a role in the poor neurological outcome of children with these encephalopathies.     

Active neocortical processes during quiescent sleep

The neocortex and the thalamus constitute a unified oscillatory machine during different states of vigilance. The cortically generated slow sleep oscillation has the virtue of grouping other sleep rhythms, including those arising in the thalamus, within complex wave-sequences. Despite the coherent oscillatory activity in corticothalamic circuits, on the functional side there is dissociation between thalamus and neocortex during sleep. While dorsal thalamic neurons undergo inhibitory processes induced by prolonged spikebursts of GABAergic thalamic reticular neurons, the cortex displays, periodically, a rich spontaneous activity and preserves the capacity to process internally generated signals. Simultaneous intracellular recordings from thalamic and cortical neurons show that short-term plasticity processes occur after prolonged and rhythmic spike-bursts fired by thalamic and cortical neurons during slow-wave sleep oscillations. This may serve to support resonant phenomena and reorganize corticothalamic circuitry.     

Relation between the electrical and mechanical activity of the stomach. In situ study of the anesthetized rat

The relations between the electrical and mechanical activity of the corpus and the antrum have been studied by means of several microelectrodes and enterographic transducer under binocular control (X 5) in anaesthetized rats (pentobarbital Na, 4 mg/kg). The recording period starts from 30 min after the onset of anaesthesia. This time corresponds to the release of the post operative inhibitions. Several rhythms of slow components have been in evidence thanks to a long time constant (5 sec): the dominant component with his frequency 4.04 +/- 1.06 c/min (n = 302 values). This frequency increases (5.11 +/- 1.3 c/min) during the antropyloric evacuation. Other rhythmic components of smaller amplitude (less than 200 microV) and frequency ranging between 7-16 c/min have been seen in quiescent conditions. In contractile state, the incidence of such rhythms decreases. The weakest manifestations of mechanical activity consist of small rhythmic variations of volume, the frequency corresponding to the main gastric rhythm of 4.5 c/min; however any spiking activity is observed. The second step of activity is the peristalsis (speed: 1 mm/sec), the circular contractility is accompanied by small spikes (less than 200 microV) in short salves. The third step is marked by the antral contraction with an important volume of variation, spike bursts of greater amplitude and biphasic slow wave are recorded. The antral activity is followed by a break of the main rhythm activity during 20 sec. These activities appear as a result from a structuration of local oscillators of relatively high frequency, in this species.     

Functional interrelations of brain structures in the cat during the generation of rhythmic activity. III. Cluster analysis of rhythmic indices

The functional interrelationships of the brain structures of freely moving cats in generation of rhythmic EEG activity during the states of drowsiness and light sleep were evaluated using the claster analysis of mean values indexes of rhythms in different structures as well as correlation coefficients between them in time. It was shown that according these parameters visual cortical areas and lateral geniculate body appeared in different clusters. Lateral geniculate body suggested not to be the only pacemaker of EEG rhythms in visual cortex. The wide convergence of subcortical inputs to the visual cortex and possibility of autonomic generation of EEG rhythms at the cortical level are discussed as putative mechanisms of dissociation of EEG activities in visual cortex and thalamus.     

Self-sustained rhythmic spike and wave activity and response of glial and nerve cells in the cat sensorimotor cortex

During acute experiments on unanesthetized cats, immobilized with myorelaxants, it was found that during rhythmic stimulation (8–14 Hz, duration: 10 sec) of the ventroposterolateral thalamic nucleus brief hyperpolarization is succeeded by depolarization in the pyramidal neurons of the sensorimotor cortex. Following this depolarization, rhythmic (approximately 3 Hz) paroxysmal depolarizing shifts in membrane potential are produced by ending stimulation, succeeded by protracted hyperpolarization and termination of rhythmic wave activity. Depolarization only is observed in glial cells, however, while hyperpolarization sets in after hyperpolarization is completed in the neurons. It is suggested that long-term changes in the membrane potential of cortical cells could make some contribution to the setting up and termination of rhythmic spike and wave activity.I. S. Beritashvili Institute of Physiology, Academy of Sciences of the Georgian SSR, Tbilisi. Translated from Neirofiziologiya, Vol. 18, No. 3, pp. 319–325, May–June, 1986.     

Ontogenetic development of convulsant action of Ro 5-3663 in the rat

Motor seizures were induced by Ro 5-3663 in 156 male albino rats aged 7,12,18,25, and 90 days. Both minimal and maximal seizures could be elicited in 18-day-old and older animals, whereas only maximal seizures were induced in the two youngest groups. ECoG changes were studied in other 21 young rats. First changes induced by Ro 5-3663 were formed by isolated sharp waves in 7- and 12-day-old rats and by episodes of rhythmic activity in older animals. An imperfect form of this rhythmic activity could be seen even in 12-day-old rats. Ictal ECoG activity exhibited an increase in frequency of individual graphoelements, in generalization and in synchronization of activity among different cortical regions with maturation. Correlation between motor and ECoG phenomena was poor in 7-day-old rats and ameliorated with age but it never reached perfection. The actions of Ro 5-3663 are identical with those induced by metrazol but they differ from those elicited by bicuculline or 3-mercaptopropionic acid.     

Ontogenetic development of electrocorticogram in the rat

Spontaneous electrocorticogram (ECoG) was recorded in frontal (sensorimotor) temporal (auditory) and occipital (visual) cortical regions of 86 male rats (immobilized with d-tubocurarine) aged from 3 days to adulthood. Activity which could be classified as ECoG was for the first time recorded in 5-day-old rats; it was formed by groups of slow waves with unstable frequency intermingled with periods of isoelectric line. Discontinuous ECoG activity was regularly registered even in 10-day-old rats, exceptionally in 12-day-old rats. During further maturation of the continuous ECoG an increase in frequency and an establishment of a basic rhythmic activity synchronous over both hemispheres took place, so that 25- and 30-day-old rats did not differ from the adult ones. Autocorrelagrams and power frequency spectra demonstrated a broad frequency range of the basic rhythm as well as delay in the development of occipital cortical areas in comparison to frontal areas.     

Influence of propranolol on rhythmic electrocorticographic activity induced by metrazol in rats

Influence of propranolol (5 mg/kg i.p.) on rhythmic metrazol activity (RMA) was studied in 11 male albino rats with chronically implanted cortical as well as subcortical (thalamic ventrobasal complex and dorsal hippocampus) electrodes. Metrazol was injected subcutaneously at a low dose of 30 mg/kg. Another group of five rats was used to study the action of propranolol on spontaneously appearing episodes of rhythmic spikes as well as on vigilance. The incidence of both rhythmic metrazol activity and episodes was significantly increased by propranolol. The latency to the first burst of rhythmic metrazol activity and to the maximum of its incidence was significantly shortened by propranolol. Propranolol also increased the incidence of relaxed wakefulness and delayed the appearance of slow wave sleep. The facilitation of RMA and spontaneous episodes could not be explained only by the increased amount of relaxed wakefulness, i.e. the vigilance level necessary for these two phenomena, because these changes did not coincide in time. In two animals, the combination of propranolol and metrazol led to the appearance of ictal activity which was sometimes accompanied by partial clonic convulsions. This phenomenon was never seen after metrazol alone (30 mg/kg s.c.) in control recordings. Propranolol was found to potentiate the possible models of human absences--spontaneous episodes, RMA and minimal clonic seizures.     

New aspects of the neurophysiological mechanism of the action of nootropic preparations

The influence of nootropic drugs on EEG spectral power of the cortex and hippocamp was studied in resting rats. All these drugs had a specific action on EEG spectral power, causing an increase and stabilization of maximum basic distribution peak of the EEG spectral power. Such action may be attributed to better organization of rhythmic activity in theta-range. The drugs also decreased interhemispheric asymmetry of the cortical and hippocampal EEG. The authors suggest that the increase and improvement of the basic rhythmic activity in the brain and an increased level of distant (spatial) synchronization form the basis for the nootropic drug effect.     

Electrical activity of the visual cortex under conditions of altered monoamine levels in the brain of animals

In experiments on 8 rabbits and 12 rats changes in electrograms of the visual cortex of alert animals were studied under photic stimulation in conditions of pharmacological action on monoamine (MA) brain systems. After injection of MA precursors (5-oxitriptophane and d, 1-dioxiphenylalanine) following phenomena were observed: a) decrease of the amplitude of the averaged evoked potentials to rhythmic photic stimuli (1-20 imp. sec.-1); b) an enhancement of fast (15-25 Hz) oscillations in the cortical spontaneous electrical activity and weakening and modification of the effects of the blockader of synthesis of MA-alpha-methyl-dioxiphenylalanine. Under light stimulation potentiation of MA precursors effects was observed in the frequency spectra of electrocorticograms. In the same conditions the specificity of action of cathecholamines precursor was revealed in the form of an increase of power of rhythms of 5-7 Hz and it; decrease in 2-3 Hz. Possible mechanisms of the revealed phenomena are discussed.     

Rhythmic after-discharge in the cat cerebral cortex and deep brain structures during stimulation of the claustrum

Effects of stimulation of the claustrum and caudate nucleus in the neocortex and various deep brain structures were studied in acute experiments on unanesthetized cats immobilized with tubocurarine. A rhythmic after discharge appeared in neocortical areas 4–7 and 18 (according to Reinoso-Suarez' atlas), and also in the caudate nucleus and various parts of the thalamus. A similar discharge also was observed in the claustrum itself. Diencephalic brain section at the level of the ventral anterior nucleus weakened but did not completely abolish the cortical rhythmic after-discharge in the anterior regions of the neocortex evoked by stimulation of the claustrum. This discharge was completely blocked after sagittal brain section between the claustrum and the rest of the thalamus.I. S. Beritashvili Institute of Physiology, Academy of Sciences of the Georgian SSR, Tbilisi. Translated from Neirofiziologiya, Vol. 15, No. 2, pp. 121–127, March–April, 1983.     

Effect of diazepam on the electroencephalographic pattern and vigilance of unanaesthetized and curarized rats with a chronic cobalt-gelatin focus.

The author studied the effect of diazepam in doses of 1 and 3 mg/kg on rats with a chronic cortical cobalt-gelatin focus and implanted cortical and subcortical electrodes. Focal spike activity localized at the site of the focus and hypersynchronous generalized episodes of spikes (and waves) of 8--9/sec frequency were studied in the electroencephalogram and the main phases of vigilance (waking, telencephalic slow waves/SWS/and REM sleep) after diazepam were evaluated. The effect of diazepam on rats temporarily immobilized with tubocurarine was also evaluated. 1. Focal spike activity during sleep was mildly inhibited by diazepam. If present in the waking state, it was markedly inhibited. 2. The number of episodes diminished significantly after diazepam. The maximum decrease occurred 30--45 minutes after administering diazepam and after that they slowly recovered. 3. Diazepam did not inhibit alteration of the phases of vigilance, but there was an increase in the proportion of telencephalic sleep with large numbers of spidles of 12--14/sec frequency and the incidence of REM phases rose by 250--300%. 4. Diazepam brought no renewal of the episodes which disappeared from the waking EEG recording of rats with a chronic focus temporarily immobilized with tubocurarine. Its administration was followed mostly by sleep activity with spindles. 5. Despite certain effects in common (disappearance of episodes), the action of diazepam differs from that of barbiturates in many respects and is effected by different mechanisms.     

Grey Matter Atrophy in Multiple Sclerosis: Clinical Interpretation Depends on Choice of Analysis Method

Background

Studies disagree on the location of grey matter (GM) atrophy in the multiple sclerosis (MS) brain.

Aim

To examine the consistency between FSL, FreeSurfer, SPM for GM atrophy measurement (for volumes, patient/control discrimination, and correlations with cognition).

Materials and Methods

127 MS patients and 50 controls were included and cortical and deep grey matter (DGM) volumetrics were performed. Consistency of volumes was assessed with Intraclass Correlation Coefficient/ICC. Consistency of patients/controls discrimination was assessed with Cohen’s d, t-tests, MANOVA and a penalized double-loop logistic classifier. Consistency of association with cognition was assessed with Pearson correlation coefficient and ANOVA. Voxel-based morphometry (SPM-VBM and FSL-VBM) and vertex-wise FreeSurfer were used for group-level comparisons.

Results

The highest volumetry ICC were between SPM and FreeSurfer for cortical regions, and the lowest between SPM and FreeSurfer for DGM. The caudate nucleus and temporal lobes had high consistency between all software, while amygdala had lowest volumetric consistency. Consistency of patients/controls discrimination was largest in the DGM for all software, especially for thalamus and pallidum. The penalized double-loop logistic classifier most often selected the thalamus, pallidum and amygdala for all software. FSL yielded the largest number of significant correlations. DGM yielded stronger correlations with cognition than cortical volumes. Bilateral putamen and left insula volumes correlated with cognition using all methods.

Conclusion

GM volumes from FreeSurfer, FSL and SPM are different, especially for cortical regions. While group-level separation between MS and controls is comparable, correlations between regional GM volumes and clinical/cognitive variables in MS should be cautiously interpreted.     

Organization of the spatial-temporal relationships of cerebral electrical processes in children during exposure to verbel commands]

An EEG cross-correlation analysis has shown that in children aged four to five years higher sensory analysis of verbal commands and their meaning was reflected in the nature of synchronous interactions between oscillatory processes and their spatial-temporal patterns. At the moment of perception of the command "listen" highly synchronous synphasic relations were recorded between biopotentials in the associative infero-parietal cortex and projection temporal centres of the left hemisphere. Oscillations of the parietal areas preceded the rhythms of the occipital, motor and frontal lobes in the left hemisphere; slow oscillations with a 3 osc/sec frequency predominated, and the intensity of the periodic processes increased. The command "look" evoked a high degree of synchronous synphasic relations of biopotentials in the parietal-occipital cortical parts of both hemispheres; oscillations with 6 osc/sec frequency predominated; their intensity rose; synphasic relations of oscillations in parietal and motor and temporal centres grew more manifest, while the rhythmic activity in the parietal zones preceded the potentials in the frontal lobes of both hemispheres.