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[Spatial synchronization of cerebral cortical potentals at different levels of functioning of short-term verbal memory].

Spatial synchronization of cortical biopotentials was studied at different levels of the functioning of short-term verbal memory. In the phases prior to and during presentation of information the general level of distant synchronization in the cortex at a high functional state of the mnemical mechanism is higher than at a low state. In the phases following presentation and during reproduction, the relations are reverse. The enhancement of distant synchronization involves primarily the posterior parts of the right hemisphere, while the decrease comprises all the cortical areas, with some predominance of this effect in the anterior areas.

Cerebral Cortex↗

Neocortical seizures: initiation, development and cessation.

Different forms of electrical paroxysms in experimental animals mimic the patterns of absence seizures associated with spike-wave complexes at approximately 3 Hz and of Lennox-Gastaut seizures with spike-wave or polyspike-wave complexes at approximately 1.5-2.5 Hz, intermingled with fast runs at 10-20 Hz. Both these types of electrical seizures are preferentially generated during slow-wave sleep. Here, we challenge the hypothesis of a subcortical pacemaker that would account for suddenly generalized spike-wave seizures as well as the idea of an exclusive role of synaptic excitation in the generation of paroxysmal depolarizing components, and we focus on three points, based on multiple intracellular and field potential recordings in vivo that are corroborated by some clinical studies: (a) the role of neocortical bursting neurons, especially fast-rhythmic-bursting neurons, and of very fast oscillations (ripples, 80-200 Hz) in seizure initiation; (b) the cortical origin of both these types of electrical paroxysms, the synaptic propagation of seizures from one to other, local and distant, cortical sites, finally reaching the thalamus, where the synchronous cortical firing excites thalamic reticular inhibitory neurons and thus leads to steady hyperpolarization and phasic inhibitory postsynaptic potentials in a majority of thalamocortical neurons, which might explain the obliteration of signals from the external world and the unconsciousness during absence seizures; and (c) the cessation of seizures, whose cellular mechanisms have only begun to be investigated and remain an open avenue for research.

Animals↗

Thalamic regulation of epileptic spike and wave discharges.

Idiopathic generalized epilepsy is characterized by the spontaneous occurrence on the electroencephalogram of bilateral synchronous spike and wave discharges that involve the entire cortical mantle from the very onset. A central role in cortical synchronization is played by the thalamus, and in particular by the reticularis thalami nucleus, which is regarded as the pacemaker structure for the rhythmic cortical oscillations called spindle activity. Several studies have suggested that the network mechanisms which underlie spindle generation can also account for spike and wave discharges. Experimental investigations on genetic animal models of generalized epilepsy, in which seizures occur spontaneously in the absence of any inductive agent, confirmed that the thalamo-cortical system is involved in spike and wave discharge generation. According to these studies a genetically determined dysfunction in reticularis thalami neurons may alter the electroresponsiveness of the developing thalamo cortical system and cause a persistent state of abnormal excitation.

Animals↗

Input and frequency-specific entrainment of postsynaptic firing by IPSPs of perisomatic or dendritic origin.

Correlated activity of cortical neurons underlies cognitive processes. Networks of several distinct classes of gamma-aminobutyric acid (GABA)ergic interneurons are capable of synchronizing cortical neurons at behaviourally relevant frequencies. Here we show that perisomatic and dendritic GABAergic inputs provided by two classes of GABAergic cells, fast spiking and bitufted interneurons, respectively, entrain the timing of postsynaptic spikes differentially in both pyramidal cells and interneurons at beta and gamma frequencies. Entrainment of pyramidal as well as regular spiking non-pyramidal cells was input site and inhibitory postsynaptic potential frequency dependent. Gamma frequency input from fast spiking cells entrained pyramidal cells on the positive phase of an intrinsic cellular theta oscillation, whereas input from bitufted cells was most effective in gamma frequency entrainment on the negative phase of the theta oscillation. The discharge of regular spiking interneurons was phased at gamma frequency by dendritic input from bitufted cells, but not by perisomatic input from fast spiking cells. Action potentials in fast spiking GABAergic neurons were phased at gamma frequency by both other fast spiking and bitufted cells, regardless of whether the presynaptic GABAergic input was at gamma or beta frequency. The interaction of cell type-specific intrinsic properties and location-selective GABAergic inputs could result in a spatio-temporally regulated synchronization and gating of cortical spike propagation in the network.

Action Potentials↗

Spike-wave rhythms in cat cortex induced by parenteral penicillin. I. Electroencephalographic features.

Surface and depth recordings were made in 21 cats with generalized, parenteral penicillin induced epileptiform activity often assuming spike-wave forms, to obtain information on the structural substrate of "spontaneous" spike-wave rhythms. Recordings were made from neocortex, medial and lateral thalamus, hippocampus and brainstem reticular formation. Epileptiform activity first appeared in cortex and subsequently projected to depth structures. Occasionally, focal discharges could be seen in subcortical structures, but these generally did not spread to cortex. No consistent "pacemaker" was identified in cortex or depth. Bilateral applications of penicillin to cortex produced synchronous spike-wave bursts. In contrast, ventriculocisternal perfusion of penicillin solutions yielded synchronous cortical potentials which differed clearly in morphology and frequency from parenterally induced spike-wave bursts. During generalized activity, transcortical, intrahemispheric lesions interfered with ipsilateral synchrony. After transcortical section, projection of localized cortical bursts to thalamus did not necessarily result in "recruitment" of diffuse cortical regions into epileptiform activity. These results emphasize the importance of cortical circuitry and corticocortical connections in the genesis and synchronization of spike-wave rhythms.

Animals↗

Single locus mutations in mice expressing generalized spike-wave absence epilepsies.

Studies in mutant mice are beginning to reveal important general principles regarding the heredity of the spike-wave cortical synchronization trait. First, a defect at a single gene locus is sufficient to produce a generalized spike-wave seizure disorder. Second, the EEG pattern itself is genetically heterogeneous, and can arise from mutations in at least five independent loci. Third, the intervening cellular excitability mechanisms underlying the generation of spike-wave cortical discharges are not identical. Fourth, each of the mutant genes gives rise to syndromes that can differ in their seizure frequency, sensitivity to antiepileptic drugs, and severity of the associated neurological phenotype. Fifth, primary defects can be distinguished from secondary cellular alterations resulting from pathological neuronal synchronization. The patterns of these secondary changes vary according to the specific mutant allele, and may give rise to distinctive secondary phenotypes. The reproducibility of these defined genetic models may facilitate age-dependent antiepileptic drug discovery by defining novel targets for therapy at different developmental stages of the seizure disorder.

Action Potentials↗

[Electroencephalographic analysis of the central action of halonal].

The experiments on rabbits revealed the depressant effect of anticonvulsant drug halonal on spontaneous bioelectrical activity and electroexcitability of the motor area of the cerebral cortex, caudate nucleus, intralaminar nuclei of the thalamus and midbrain reticular formation. The drug exerts no effect on the amygdala and hippocamp. The mechanism of the anticonvulsant effect of halonal involves inhibition of the caudo-thalamo-cortical synchronizing system that presumably disorders the occurrence of the hypersynchronous charge in the cortical neurons and prevents the development of a convulsive fit.

Animals↗

Mutational analysis of inherited epilepsies.

Single-gene mutations in mice initiate specific heritable neuronal diseases featuring different patterns of epilepsy. Thirteen chromosomal loci for convulsive seizures and four loci for spike-wave seizures have been assigned. Within this genetic framework, a few general principles are emerging. Mutations located on different chromosomes may result in identical seizure patterns. Interactions between specific genes, demonstrated by the synthesis of compound heterozygotes, can express intermediate syndromes. Interactions with unknown genes in the background can mask neurological disease expression. Analysis of the cellular phenotypes of epileptic mutants is a direct strategy to define naturally occurring defects in central synaptic pathways involved in cortical synchronization. In one allele of the tottering locus, a pathogenetic lesion linking noradrenergic hyperinnervation with cortical spike-wave discharges has been identified. The tottering gene initiates an overgrowth within all target innervation areas of axon terminals originating from the locus coeruleus (LC). Selective neonatal denervation of the excess noradrenergic axons permanently prevents the subsequent appearance of cortical spike-wave seizures in the adult animal. Partial lesions of central noradrenergic afferent fibers in adults temporarily reverse the seizure disorder. Other criteria defining the relationship between the mutant gene and the electrophysiologic traits and the role of central noradrenergic pathways in neuronal synchronization are reviewed. Isolating and tracing the developmental expression of epileptic mutations permits a formal classification of gene-linked excitability defects, a derivation of basic rules governing their inheritance, and the design of strategies to correct the gene error. By allowing phenotypic comparisons with over 60 known human inherited neurological diseases associated with seizures, these models may directly contribute to advances in the clinical management of epileptic gene expression.

Action Potentials↗

Chattering cells: superficial pyramidal neurons contributing to the generation of synchronous oscillations in the visual cortex.

In response to visual stimulation, a subset of neurons in the striate and prestriate cortex displays synchronous rhythmic firing in the gamma frequency band (20 to 70 hertz). This finding has raised two fundamental questions: What is the functional significance of synchronous gamma-band activity and how is it generated? This report addresses the second of these two questions. By means of intracellular recording and staining of single cells in the cat striate cortex in vivo, a biophysically distinct class of pyramidal neuron termed "chattering cells" is described. These neurons are located in the superficial layers of the cortex, intrinsically generate 20- to 70-hertz repetitive burst firing in response to suprathreshold depolarizing current injection, and exhibit pronounced oscillations in membrane potential during visual stimulation that are largely absent during periods of spontaneous activity. These properties suggest that chattering cells may make a substantial intracortical contribution to the generation of synchronous cortical oscillations and thus participate in the recruitment of large populations of cells into synchronously firing assemblies.

Action Potentials↗

[Excitability of the senso-motor cortex and red nucleus of rabbits with different levels of cortical potential spatial synchronization].

The motor reaction of the rabbit to the threshold electrical stimulation of the sensomotor cortex and red nucleus was studied to determine excitability of these structures. Under conditions of the computer-controlled experiment the excitability of the two structures was compardd for situations characterized by different levels of cortical potential correlation. An increase in the spatial synchronization of the cortical potentials is shown to be accompanied by intensification in excitability of the sensomotor cortex and red nucleus. This intensification seems to be one of possible neurophysiological mechanisms of the probability increase for the effector reaction to sensory stimuli when the cortical spatial synchronization rises.

Animals↗

Where and how does grammatically geared processing take place-and why is Broca's area often involved. A coordinated fMRI/ERBP study of language processing.

We address the possibility of combining the results from hemodynamic and electrophysiological methods for the study of cognitive processing of language. The hemodynamic method we use is Event-Related fMRI, and the electrophysiological method measures Event-Related Band Power (ERBP) of the EEG signal. The experimental technique allows us to approach the relation between cortical structure and cognitive function in a sophisticated way. In particular, we can formulate original working hypotheses about the language-induced changes in the ongoing brain dynamics. We show, on the basis of electrophysiological data collected in an experiment on language production, that synchronized cortical networks code cognitive processes induced by language in form of power modulations of specific frequency bands. The hemodynamic (fMRI) data collected in the same task point to the existence of a central processor for the phrase structure assignment. We conceptualize such a central processor as a frequency scanner, a cortical device designed to pick up synchronized brain activity over a specific range of frequencies. We discuss the experimental designs which result from this set of hypotheses and show their relevance for the models of language processing.

Adult↗

[Bioelectric brain activity in patients with neurotic disorders].

Seventy-three patients with neurotic disorders, aged 14-35 years, and 33 healthy controls have been examined using electroencephalographic method with spectral analysis of EEG, which has been conducted on the Brain Surfing system by the algorithm of direct Fourier transformation. The patients had changes of brain electric activity manifesting as insufficiency of thalamo-cortical synchronizing systems that caused an excessive activating effect of reticular formation on the cortex realized through extrathalamic reticular cortical and septo-hippocampal activation paths. Determinative in electrophysiological brain organization was the theta-rhythm, a marker of excessive emotional and autonomic activation, which directly correlated with an extent of personality accentuation and severity of neurotic state.

Adolescent↗

Effects of dopamine antagonists on changes in spontaneous EEG and locomotor activity in ketamine-treated rats.

We investigated the effects of dopamine antagonists on spontaneous cortical and hippocampal electroencephalographic (EEG) changes, and on hyperlocomotion in ketamine-treated rats. Ketamine (20-60 mg/kg IP) synchronized cortical EEG and desynchronized hippocampal EEG in a dose-dependent manner indicating that the drug induced a dissociation between the cortical and hippocampal EEG. These EEG changes were accompanied by an increase in spontaneous locomotor activity, which involved lack of focused direction, stereotypy, irritability and other abnormalities. Dopamine antagonists, such as haloperidol (0.3-1 mg/kg IP), and nemonapride (0.3-1 mg/kg IP), reversed the dissociation between the cortical and hippocampal EEG in ketamine (60 mg/kg IP)-treated rats. Ketamine-induced hyperlocomotion was also decreased by administration of haloperidol (0.3 and 1 mg/kg IP) or nemonapride (0.1-1 mg/kg IP). Thus, it was found that dopamine antagonists reversed the EEG alterations and behavioural changes in ketamine-treated rats.

Analysis of Variance↗

Increases in the density of parvalbumin-immunoreactive neurons in anterior cingulate cortex of amphetamine-withdrawn rats: evidence for corticotropin-releasing factor in sustained elevation.

We previously reported synchronization of pyramidal neurons within prefrontal cortex of rats repeatedly exposed to amphetamine (AMPH). To test the hypothesis that cortical synchronization may be related to changes in local GABA signaling, we used antibodies specific for parvalbumin (PV), calbindin D28k (CB) and calretinin (CR) as selective labels for three distinct GABA interneuron classes in the anterior cingulate cortex (ACC) of similarly treated rats. We observed a selective increase in the density of PV-immunoreactive (ir), but not CB-ir or CR-ir, neurons in the ACC of AMPH-treated rats at both 1 day and 7 day withdrawal. Increased density of PV-ir GABA interneurons in the ACC at 1 day withdrawal was reproduced in rats repeatedly injected with apomorphine or with SKF-38393. Thus, the critical role of DA receptors during AMPH exposure is evident. However, DA receptor activation did not appear to account for the PV up-regulation in AMPH-treated rats at 7 day withdrawal. Significantly higher numbers of pericellular basket-like puncta immunoreactive for corticotropin-releasing factor (CRF) were observed in the ACC of AMPH rats at 7 day withdrawal. Combined dual immunofluorescence and confocal microscopy further revealed that CRF-ir puncta made possible pericellular contacts on PV-ir (not CB-, CR- or glutamate-ir) cell bodies. A potential cellular mechanism seems to emerge that CRF-ir terminals, that may be underdetected under normal conditions due to low activity levels, may be functionally activated during psychostimulant withdrawal, thereby altering local GABAergic signaling.

Amphetamine↗

Oscillatory and non-oscillatory synchronizations in the visual cortex and their possible roles in associations of visual features.

It was postulated that the perceived association of visual features is based on the synchronization of those neural signals that are activated by a coherent visual object. Two types of synchronized cortical signals were found by us in cat and monkey visual cortex, and were proposed as candidates for feature association: (1) stimulus-locked signals, evoked by transient retinal stimulation, and typically non-rhythmic; (2) oscillatory signals, induced by sustained stimuli, and typically not locked in their oscillation phases to stimulus events. Both types of signals can occur synchronously in those neurons that are activated by a common stimulus. Synchronized activities were found in paired recordings within vertical cortex columns, in separate columns of the same cortical area, and even between different cortical areas or hemispheres. The average phase difference between such common oscillatory events was typically close to zero (< 1 msec mean +/- 2 msec S.D.). For the dependence of synchronization from stimulus and receptive field properties, a preliminary 'rule' can be given: the coherence of fast oscillations in separate cortical assemblies depends inversely on the 'coding distance' between the assemblies' RF properties, but directly on the degree of overlap between the assemblies' respective coding properties and the features of a common stimulus. This means that oscillatory events in any two assemblies, in the same or in different cortical areas or hemispheres, are more closely correlated the more similar are their receptive field properties, and the better a common stimulus activates the assemblies simultaneously. Our results can explain some neural mechanisms of perceptual feature-linking, including mutual enhancement among similar, spatially and temporally dispersed features, definitions of spatial and temporal continuity, scene segmentation, and figure-ground discrimination. We further propose that mutual enhancement and synchronization of cell activities are general principles of temporal coding by assemblies, that are also used within and among other sensory modalities as well as between cortical sensory and motor systems.

Animals↗

Dynamic synchronization between multiple cortical motor areas and muscle activity in phasic voluntary movements.

To study the functional role of synchronized neuronal activity in the human motor system, we simultaneously recorded cortical activity by high-resolution electroencephalography (EEG) and electromyographic (EMG) activity of the activated muscle during a phasic voluntary movement in seven healthy subjects. Here, we present evidence for dynamic beta-range (16-28 Hz) synchronization between cortical activity and muscle activity, starting after termination of the movement. In the same time range, increased tonic activity in the activated muscle was found. During the movement execution a low-frequency (2-14 Hz) synchronization was found. Using a novel analysis, phase-reference analysis, we were able to extract the EMG-coherent EEG maps for both, low- and high-frequency beta range synchronization. The electrical source reconstruction of the EMG-coherent EEG maps was performed with respect to the individual brain morphology from magnetic resonance imaging (MRI) using a distributed source model (cortical current density analysis) and a realistic head model. The generators of the beta-range synchronization were not only located in the primary motor area, but also in premotor areas. The generators of the low-frequency synchronization were also located in the primary motor and in premotor areas, but with additional participation of the medial premotor area. These findings suggest that the dynamic beta-range synchronization between multiple cortical areas and activated muscles reflects the transition of the collective motor network into a new equilibrium state, possibly related to higher demands on attention, while the low-frequency synchronization is related to the movement execution.

Adult↗

Modification by tricyclic antidepressants of cortical EEG changes induced by clonidine in conscious rats.

The effects of various tricyclic antidepressants on clonidine-induced electroencephalographic changes were investigated in rats. The EEG pattern of conscious rats was recorded by means of bipolar electrodes, implanted chronically. Clonidine (50, 150 and 300 micrograms/kg) not only synchronized cortical EEG pattern but also evoked signs of behavioural depression within 15 min of its administration. Pretreatment with imipramine, desipramine, trimipramine, amitriptyline, nortriptyline and doxepin reduced clonidine-induced EEG synchrony without showing any effects per se. Acute treatment with tricyclic antidepressants failed to modify but, chronic treatment abolished the clonidine-induced behavioural depressive signs. Chronic administration of tricyclic antidepressants (10 mg/kg/day) evoked more pronounced antagonism of the EEG effects of clonidine. Yohimbine (200 micrograms/kg) pretreatment inhibited both, clonidine-induced EEG synchrony and behavioural effects. Guanfacine as well as B-HT 920, elicited clonidine-like effects on cortical EEG pattern and behaviour. The present data suggests that antagonism of clonidine-induced EEG synchronization in conscious animals could serve as a useful test for screening of antidepressant drugs.

Animals↗