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Involvement of electrical coupling in the in vivo ictal epileptiform activity induced by 4-aminopyridine in the neocortex.

In the present study we have investigated the possible role of gap junctions in the induction and manifestation of 4-aminopyridine-induced acute seizure activity both at the primary focus and at the mirror focus in anaesthetized rats by combining electrophysiological, pharmacological and molecular biological techniques. In the course of the intracellular recordings, unusual firing patterns that are assumed to be mediated by electrical coupling and appearing either randomly or in close time-locked manner with the ictal discharges were observed. In another series of experiments, a significant decrease in the intensity of seizure activity of the already active epileptic foci was detected when electrical synaptic transmission was blocked by carbenoxolone either at the primary focus or at the mirror focus. When electrical synaptic transmission was depressed relative to the initial baseline prior to the induction of epileptic focus, only a mild influence on the induction of seizure discharges occurred. The role of the gap junctional communication in the epileptiform activity was further investigated by following the expression pattern of two connexin genes. Both, connexin-32 and connexin-43 mRNA levels were significantly elevated at the primary focus as well as at the mirror focus, after 60 min of repeated ictal discharges. We conclude that gap junction communication probably became a part of the neuronal synchronization both in the primary and in the secondarily-induced acute epileptiform activity in the neocortex in vivo. These results, together with earlier observations, indicate a direction for the development of new drugs targeting gap junctions for therapeutic intervention.

4-Aminopyridine↗

Psychophysiological evidence of altered neural synchronization in cannabis use: relationship to schizotypy.

OBJECTIVE: Cannabis use may produce neurophysiological disturbances similar to those observed in schizophrenia, particularly in relation to altered neural synchronization. Therefore, the current experiment examined the effect of cannabis use on EEG neural synchronization using the auditory steady-state evoked potential. METHOD: Auditory steady-state evoked potentials were assessed using varying rates of stimulation (auditory click-trains of 20, 30, 40 Hz) in current cannabis users (N=17) and drug-naive comparison subjects (N=16). EEG spectral power and signal-to-noise ratio at each stimulation frequency were compared between groups. RESULTS: Cannabis users showed decreased EEG power and signal-to-noise ratio at the stimulation frequency of 20 Hz. In addition, current cannabis users demonstrated increased schizotypal personality characteristics as assessed with the Schizotypal Personality Questionnaire, which positively correlated with total years of cannabis use. Finally, within the cannabis group, 20-Hz power values were negatively correlated with Schizotypal Personality Questionnaire scores. CONCLUSIONS: These data provide evidence for neural synchronization and early-stage sensory processing deficits in cannabis use. This finding, along with the observed increased rates of schizotypy in cannabis users, adds support for a cannabinoid link to schizophrenia spectrum disorders.

Acoustic Stimulation↗

Rhythmicity, randomness and synchrony in climbing fiber signals.

The role of the climbing fiber input to the cerebellum has been enigmatic, with recent studies focusing on its temporal and spatial firing patterns. Debate remains as to whether climbing fibers provide a periodic clock for coordinating movements or lead to long-term modification of Purkinje cell activity as the basis of motor learning. Rhythmic and synchronous activity of climbing fibers can cause movements at the same frequency in some preparations, suggesting a role in motor timing. However, in awake monkeys climbing fiber signals have been reported to occur at random, presenting a problem for clock theories. Yet synchronous patterns of discharge are consistently observed among several Purkinje cells within a narrow parasagittal longitudinal band. Here, we review recent experimental and theoretical studies and attempt to provide a coherent account of the interplay between rhythmicity, randomness and synchrony in climbing fiber activity, with a particular reference to studies in chaos.

Animals↗

Recruitment of GABAergic inhibition and synchronization of inhibitory interneurons in rat neocortex.

Intracellular recordings were obtained from pyramidal and interneuronal cells in rat neocortical slices to examine the recruitment of GABAergic inhibition and inhibitory interneurons. In the presence of the convulsant agent 4-aminopyridine (4-AP), after excitatory amino acid (EAA) ionotropic transmission was blocked, large-amplitude triphasic inhibitory postsynaptic potentials (IPSPs) occurred rhythmically (every 10-40 s) and synchronously in pyramidal neurons. After exposure to the gamma-aminobutyric acid-A (GABA(A)) receptor antagonist picrotoxin, large-amplitude monophasic slow IPSPs persisted in these cells. In the presence of 4-AP and EAA blockers, interneurons showed periodic spike firing. Although some spikes rode on an underlying synaptic depolarization, much of the rhythmic firing consisted of spikes having highly variable amplitudes, arising abruptly from baseline, even during hyperpolarization. The spike firing and depolarizing synaptic potentials were completely suppressed by picrotoxin exposure, although monophasic slow IPSPs persisted in interneurons. This suggests that this subset of interneurons may participate in generating fast GABA(A) IPSPs, but not slow GABA(B) IPSPs. Cell morphology was confirmed by intracellular injection of neurobiotin or the fluorescent dye Lucifer yellow CH. Dye injection into interneurons often (>70%) resulted in the labeling of two to six cells (dye coupling). These findings suggest that GABA(A)ergic neurons may be synchronized via recurrent collaterals through the depolarizing action of synaptically activated GABA(A) receptors and a mechanism involving electrotonic coupling. Although inhibitory neurons mediating GABA(B) IPSPs may be entrained by the excitatory GABA(A) mechanism, they appear to be a separate subset of GABAergic neurons capable of functioning independently with autonomous pacing.

Animals↗

Attenuation of regional differentiation of sympathetic nerve activity during sleep in humans.

The purpose of the present study was to clarify how the regional differentiation of sympathetic nerve activity (SNA) is modified during natural sleep in humans. In humans, muscle and skin sympathetic nerve activities (MSNA, SSNA) have been reported to discharge independently according to a regional differentiation of SNA during wakefulness. However, in natural sleep, MSNA and SSNA have been documented to synchronize during sleep stage 2 (Rechtschaffen and Kales). In the present study, we measured MSNA and SSNA simultaneously using a double recording technique of microneurography in eight healthy volunteers during natural sleep, and analyzed how MSNA and SSNA can be synchronized. We found that the synchronicity of MSNA and SSNA was accelerated in correlation with the deepening of the non-rapid eye movement (nonREM) sleep stages. We also documented that the burst properties of MSNA different from those of SSNA in wakefulness become similar to those of SSNA in the sleep stage, and MSNA synchronizes with SSNA. The synchronicity of MSNA and SSNA is presumably caused by a reduced effect of central inhibitory baroreflex pathways on MSNA during nonREM sleep. The present findings suggest that the regional differentiation of sympathetic nerve activity is attenuated with the deepening of nonREM sleep stages.

Adult↗

The medullary cerebrovascular vasodilator area mediates cerebrovascular vasodilation and electroencephalogram synchronization elicited from cerebellar fastigial nucleus in Sprague-Dawley rats.

We investigated whether the medullary cerebrovasodilator area (MCVA), a region of ventral medulla mediating elevations of regional cerebral blood flow (rCBF) and electroencephalogram (EEG) synchronization elicited in cerebral cortex from stimulation of reticulospinal neurons of rostral ventrolateral medulla (RVLM), also mediates comparable responses from the cerebellar fastigial nucleus (FN). In spinalized rats, electrical stimulation of MCVA, RVLM or FN elevated rCBF and synchronized the EEG. The FN-evoked responses were significantly attenuated or blocked by bilateral lesions of MCVA. The MCVA is a novel region of medullary reticular formation mediating actions of medullary and cerebellar centers on rCBF and EEG to link visceral centers of brainstem and cerebral cortex.

Animals↗

Temporal order of nonlinear dynamics in human brain.

In previous spectral analysis investigations, we demonstrated that the spontaneous activity of the alpha EEG is not stationary but rather shows cyclic alterations with a circa 1-min periodicity. Following the conclusion that a power increase in the alpha band implies a neuronal synchronization, and vice versa, an associated decrease of the EEG complexity was postulated. Accordingly, a rhythmic variation, i.e., a temporal order of the nonlinear dynamics with similar period length, was expected. Bipolar 4-min EEG recordings were obtained from 20 awake subjects (mean age: 23.5+/-2.5 years) with eyes closed for the EEG leads C3, C4, Oz, and Fz according to the 10-20 system. For the automatic evaluation of spontaneous alterations of complexity, a sliding computation of the so-called correlation dimension, using an analysis window length of 20 s continuously shifted by 1 s, was performed. The time series of complexity exhibited an oscillatory behavior with a mean period length of 58.7 s; the Friedman test statistic revealed no significant topological differences. For the rejection of the null hypothesis that the observed periodicity is a random one, two-group t-tests and ANOVA with repeated measures were performed, comparing the corresponding amplitudes and period lengths with those derived from 20 pseudo-random signals (taken from a multivariate Gaussian normal distribution). The mean relative change of EEG complexity was highly significantly increased (P<0.0001) compared to that of random data. Likewise, the difference of mean period lengths was also significant (P<0.01). The results indicate that the coupling strength of the neural network of the brain changes periodically, with a cyclic alteration from a central to a parallel processing mode of information, reflecting state transitions from synchronized, low-complex EEG activity to desynchronized high-complex activity, and vice versa. Various neuronal control mechanisms that may be acting as pacemakers responsible for the temporal order of such transients are discussed. A disturbance of the temporal order may be of pathophysiological significance.

Action Potentials↗

Neurophysiological study of secondary synchronous occipito-frontopolar spikes in childhood.

OBJECTIVES: We conducted this latency study to clarify the neurophysiological mechanism underlying the synchronous appearance of independent occipital and frontopolar spike discharges in childhood epilepsies. METHODS: The subjects were 13 children with localization-related epilepsies (LRE) who showed apparently synchronous occipital and frontopolar EEG spike discharges. There was idiopathic LRE in 7 children, symptomatic LRE in 4, and cryptogenic LRE and a history of cryptogenic West syndrome in one patient each. Patient ages at the time of the study ranged from 4 years 3 months to 14 years 0 month with a mean of 9 years 4 months. The EEGs were digitized at 1024 samples/s. The latency was measured between the peak of the occipital and frontopolar spike discharges. The conduction velocity was calculated by dividing the distance between the occipital and frontopolar electrodes by the latencies. RESULTS: We studied 19 EEGs including 6 serial EEGs recorded longitudinally in 5 patients. The number of occipito-frontal spike discharges available for the study ranged from 12 to 70 with an average of 36+/-17 in each EEG record. Occipital spikes always preceded the frontopolar spikes by 11.1-31.6 ms (average 19.3+/-5.4 ms). The estimated conduction velocity ranged from 6.7 to 19.2 m/s with a mean of 12.2+/-3.7 m/s. CONCLUSIONS: The synchronizing spike phenomenon we showed in this study was in the posterior to anterior direction (intrahemispheric synchrony) in contrast to that of secondary bilateral interhemispheric synchrony through the corpus callosum. It is suggested that the long occipito-frontal association fibers play a role in synchronizing both spike discharges. This secondary occipito-frontopolar synchrony should be one of the developmental EEG phenomena related to the maturation of brain, and contribute to the multiplication or diffusion of the pre-existing localized spike discharges often seen in pediatric LRE regardless of etiology.

Action Potentials↗

Gamma band activity and its synchronization reflect the dysfunctional emotional processing in alexithymic persons.

In the present study, we investigated the gamma band response and its phase synchrony between electrodes in alexithymia, which is characterized by a disability in identifying and describing feelings. Individuals with high and low alexithymia scores were selected according to the scores on the 20-item Toronto Alexithymia Scale. EEG was recorded from alexithymic and nonalexithymic persons viewing emotionally negative or neutral stimuli. Nonalexithymic persons exhibited increased gamma band power and phase synchronization at the 400-450-ms time window when processing emotionally negative stimuli. Neither enhanced gamma band power nor phase synchronization was observed in alexithymic persons in the negative emotion condition. These results suggest that gamma band activity reflects emotional processing, and alexithymic persons may have a deficit in communication between brain regions or in the utilization of memory or emotional information during the processing of emotional stimuli.

Adult↗

Stimulus-dependent neuronal oscillations and local synchronization in striate cortex of the alert cat.

Neuronal responses to visual stimuli that are correlated on a millisecond time scale are well documented in several areas of the mammalian visual cortex. This coherent activity often takes the form of synchronous rhythmic discharges ranging in frequency from 20 to 70 Hz. We performed experiments to determine the incidence and properties of this rhythmic activity in the striate cortex of alert cats and to compare this activity to similar data collected in the striate cortex of anesthetized cats. The results demonstrate that optimal visual stimuli evoke robust, locally synchronous, 20-70 Hz oscillatory responses in the striate cortex of cats that are fully alert and performing a visual fixation task. The oscillatory activity is stimulus dependent, largely absent during periods of spontaneous activity, and shows a systematic increase in frequency with increasing stimulus velocity. Thus, the synchronous oscillatory activity observed in this and earlier studies cannot be explained as an artifact of anesthesia nor as a phenomenon that occurs independent of visual stimulation. Rather, it is a robust process that is present in the alert state and is dependent on the presence and specific properties of visual stimuli.

Animals↗

Spectral and complexity features of the EEG changed by visual input in a case of subcortical stroke compared to healthy controls.

OBJECTIVE: To compare spectral and complexity characteristics of the EEG in a unique case of subcortical infarct to those seen in healthy controls. METHODS: Absolute and relative frequency spectra, theta/beta ratio, the brain symmetry index (BSI), Omega-complexity and synchronization likelihood were calculated of the EEG recorded in eyes closed and eyes open conditions. RESULTS: Increased absolute delta, theta, and Omega-complexity in these frequency bands, higher theta/beta ratios, and decreased relative beta activity were found in the side of the infarct. The BSI localized the excess of slow, and decrease of fast frequency activity to the area of ischemia. Following eyes opening the increase of fast and decrease of slow frequencies, the increase of Omega-complexity in the alpha and beta bands, and the decrease of synchronization likelihood for the fast frequency bands were reduced in the side of the infarct. CONCLUSIONS: The subcortical infarct caused ipsilaterally increased slow, and decreased fast frequency activity accompanied by decreased synchronization of slow, increased synchronization of fast frequencies. Reduced reactivity in the ischemic side was particularly apparent for complexity measures. SIGNIFICANCE: Complexity indices of the EEG are sensitive complementary measures of electrophysiological changes caused by local lesions such as subcortical stroke.

Brain Ischemia↗

Laminar pattern of synaptic inhibition during convulsive activity induced by 4-aminopyridine in neocortical slices.

1. Epileptiform activity was induced in rat neocortical brain slices by application of a low concentration (10 microM) of 4-aminopyridine (4-AP). In intracellular recordings from regular spiking neurons, the activity was characterized by prolonged, all-or-none depolarizing events, with variable delay to a threshold stimulus. 2. At this concentration, 4-AP had no measurable effect on passive electrical properties or on action-potential characteristics. 3. Paroxysmal responses in neurons of deeper layers differed markedly from those of superficial cells. In deep neurons, responses resembled those generated by neocortical neurons exposed to GABAergic blockers. A low-intensity stimulus to the white matter evoked an excitatory postsynaptic potential (EPSP) that was followed with variable latency by a paroxysmal depolarizing shift that reversed at suprathreshold membrane potentials and upon which superimposed repetitive firing was always evident. By contrast, in superficial (layer II-III) neurons, the same stimulus evoked an EPSP that was followed by a prolonged response whose late component reversed at subthreshold membrane potentials (between -50 and -80 mV). These cells rarely fired more than a single spike throughout the response. 4. Repetitive stimulation at relatively low frequencies (0.3-1 Hz) caused a gradual change in the synchronized responses that was most marked in superficial neurons. The reversal potential of the response shifted toward suprathreshold membrane potentials, and subsequently, superimposed repetitive firing became evident. These changes were not associated with measurable changes in input resistance or membrane potential.(ABSTRACT TRUNCATED AT 250 WORDS)

4-Aminopyridine↗

[Posttetanic changes in the background gamma oscillations in interhemispheric interactions].

The influence of high-frequency microstimulation (HFMS) of one of the hemispheres on the parameters of spontaneous gamma-oscillations in the neural network containing callosal cells of the motor cortex of both hemispheres. There were three modes in the background oscillation periods distribution, which corresponded to the frequencies 40-60, 70-100, and 100-200 Hz. These oscillation frequencies were also revealed after the HFMS in neural interactions of the cells, which were active before the HFMS; the frequency 40-60 Hz, which dominated before the HFMS, became even more pronounced. The same three groups of oscillation frequencies were found in the activity of cells which became active after the HFMS. The expression of oscillations, the number of oscillatory interactions, as well as the number of neuronal pairs with additional synchronization decreased after the HFMS, which suggests a decrease in synchronization. Taking into account the results of simulation experiments that the frequency of gamma-oscillations is determined by the strength of inhibitory and excitatory input, we suggest that the long-term posttetanic modifications in the efficacy of synaptic inputs of the neurons of both hemispheres underlie the observed posttetanic changes.

Action Potentials↗

Brainstem activates paroxysmal discharge in human generalized epilepsy.

In nine patients with generalized epilepsy of convulsive seizures, the excitability change of the brainstem was evaluated over the course of the interictal paroxysmal discharge (poly spike-and-wave complex, poly SWC). The evaluation was carried out by a sequential analysis of brainstem auditory evoked potentials (BAEPs) before and during one sequence of poly SWC. The characteristics of BAEPs, i.e. far-field evoked potentials, allowed the evaluation of the excitability change in the brainstem, which was not influenced by the cortical activity. The excitability in the ventral brainstem, measured with the parameters of wave-III, showed a biphasic fluctuation (deceleration--acceleration) before the onset of poly SWC (minima at -0.7+/-0.4 s). On the other hand, the excitability in the dorsal brainstem, measured with the parameters of wave-V, showed no significant difference over the course of poly SWC. The results suggest that the biphasic excitability change in the ventral brainstem is conveyed to the cortex through the ascending activating system. The excitability acceleration preceded by deceleration in the ventral brainstem probably synchronizes the cortical activity profoundly enough to produce poly SWC through the activation of intralaminar thalamic neurons.

Adolescent↗

[Event-related synchronization and desynchronization of EEG during appraisal of threatening and pleasant visual stimuli in high anxious subjects].

The 62-channel EEG was recorded while low (LA, n = 18) and high (HA, n = 18) trait-anxious subjects viewed sequentially presented neutral, threatening and pleasant IAPS stimuli. Event-related desynchronization (ERD) and synchronization (ERS) were studied in the delta, theta1, theta2, alpha1, alpha2, beta1, beta2, beta3, and gamma frequency bands. Between-group differences, related to stimulus emotionality, were linked to theta1 and theta2 bands. In the low theta at prefrontal sites in the test period of 100-700 ms after stimulus onset HA exhibited relative predominance of the left hemisphere in response to both threatening and pleasant stimuli, whereas LA yielded larger right than left hemisphere activity in response to all the three stimulus categories. In the upper theta band between group differences were associated with posterior cortical regions and the test period of 0-1000 ms after stimulus onset: HA exhibited the largest ERS to threatening, whereas LA prompted the largest ERS to pleasant stimuli. Finally, according to the ERD data, in the alpha1 band HA participants in comparison with LA revealed enhanced left hemisphere activation in response to all the stimulus categories. It is suggested that as it is indexed by theta-ERS relative predominance of the left hemisphere at prefrontal sites along with the largest bilateral activity of posterior cortical regions (i.e., enhanced higher order visual processing) to threatening stimuli could form the basis for general bias towards threatening information in HA at the very early stages of emotional processing.

Adolescent↗

[Cerebral electrical activity of children with serous meningitis].

A correlation analysis of EEGs in children 4 to 7 years of age suffering from serous meningitis revealed certain distinctions in the spatial organization of their brain biopotentials, as compared with that observed in healthy children of the same age. In the acute period of the disease the spatial synchronization of the biopotentials of the left hemisphere, especially, of the frontal and subparietal associative zones, is lowered. As the patient recovers the intercentral correlations between the right hemisphere biopotential improve. It is suggested that the right hemisphere plays a certain role in the compensation processes in the serous meningitis.

Acute Disease↗

Arousal fluctuations in non-rapid eye movement parasomnias: the role of cyclic alternating pattern as a measure of sleep instability.

Some non-rapid eye movement (NREM) parasomnias, such as sleep-walking (SW), sleep terror (ST) and, in some aspects, sleep enuresis (SE), are considered "arousal disorders" without significant polysomnographic changes in classic sleep macrostructure. The aim of our study was to evaluate sleep microstructure and oscillations of arousal level by cyclic alternating pattern (CAP) scoring in some NREM parasomnias. Nocturnal polysomnography and videotape recording was used to study 21 patients with motor and behavioral phenomena during sleep: 13 in Group A (seven SW, six ST) with delta sleep-related episodes, eight in Group B with other parasomnias (six sleep bruxism and two SE), and six healthy controls. Classic sleep macrostructural parameters were no different in the parasomniacs and controls. Compared with the controls, our patients' sleep microstructure, scored by CAP analysis, showed increases in CAP rate (a measure of NREM instability with high level of arousal oscillation), in number of the CAP cycles, and in arousals with EEG synchronization, the increases being more significant in Group A than in Group B. An increase in sleep instability and in arousal oscillation seems to be a typical microstructural feature of delta sleep-related parasomnias and probably plays a role in triggering abnormal motor episodes during sleep in these patients.

Adolescent↗

Synchrony-dependent propagation of firing rate in iteratively constructed networks in vitro.

The precise role of synchronous neuronal firing in signal encoding remains unclear. To examine what kinds of signals can be carried by synchrony, I reproduced a multilayer feedforward network of neurons in an in vitro slice preparation of rat cortex using an iterative procedure. When constant and time-varying frequency signals were delivered to the network, the firing of neurons in successive layers became progressively more synchronous. Notably, synchrony in the in vitro network developed even with uncorrelated input, persisted under a wide range of physiological conditions and was crucial for the stable propagation of rate signals. The firing rate was represented by a classical rate code in the initial layers, but switched to a synchrony-based code in the deeper layers.

Action Potentials↗