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PubMed2003

Desynchronisation of spontaneously recurrent experimental seizures proceeds with a single rhythm.

Here we investigate the temporal properties of recurrent seizure-like events (SLEs) in a low-[Mg(2+)] model of experimental epilepsy. Simultaneous intra- and extracellular electric signals were recorded in the CA3 region of rat hippocampal slices whereby cytosolic [Ca(2+)] transients were imaged by fluorescence detection. Recurrence pattern analysis was applied to give a measure of synchrony of simultaneously recorded intra- and extracellular electric signals and the SLE frequencies were extracted by complex wavelet analysis. Slices from the juvenile, but not the young adult rats, displayed several high-amplitude triplets of electric and [Ca(2+)] transients, termed paroxysmal spikes, followed by an SLE. Occurrence of the full-blown SLE was associated with decreased synaptic activity between the paroxysmal spikes that were seen as incomplete SLE starting sequences. The time series of recurrent SLEs provide evidence for a single SLE rhythm as continuously declining from about 200 Hz to below 1 Hz at the onset and termination of SLE, respectively, with an intermediate spectral discontinuity, tentatively identified with the tonic/clonic transition. All other frequency components were the harmonics of the fundamental rhythm, whereby the gamma and the theta band oscillations were not detected as separate activities. Recurrence showed decreasing temporal synchrony of intra- and extracellular signals during the SLE, suggesting that coincidence is destroyed by the SLE. Blockade of gap junctions with 200 microM carbenoxolone ceased recurrent SLEs. Release of gap junction blockade shortened both SLEs and their tonic phase indicating that persistent changes occurred via an altered gap junction coupling. We conclude that the initially precise temporal synchrony is gradually destroyed during ictal events with a single rhythm of continuously decreasing frequency. Blockade of gap junction coupling might prevent epileptic synchronisation.

Animals↗
PubMed1999

Pontine carbachol elicits multiple rapid eye movement sleep-like neural events in urethane-anaesthetized rats.

Microinjection of a cholinergic agonist, carbachol, into the pontine reticular formation of chronically instrumented intact or acutely decerebrate rats and cats has been used extensively to study rapid eye movement sleep mechanisms. In this study, we sought to develop a reduced carbachol model of rapid eye movement sleep-like neural events exhibiting multiple physiological markers of this state, and allowing for the use of invasive electrophysiological techniques. Accordingly, we investigated whether pontine carbachol could produce rapid eye movement sleep-like motor atonia and electrocortical changes in urethane-anaesthetized rats. We recorded cortical and hippocampal electroencephalograms and genioglossus and inspiratory intercostal muscle activities in 13 urethane-anaesthetized, spontaneously breathing, tracheotomized and vagotomized rats. In steady-state periods with high-voltage/low-frequency electroencephalogram activity, carbachol microinjections (15-40 nl, 10 mM) were placed in the medial pontine reticular formation. In 12 rats, carbachol elicited episodes of stereotyped hypotonia of genioglossus but not intercostal muscle activity, typical of rapid eye movement sleep, with a latency and duration of 2.2+/-0.3min (mean+/-S.E.M.) and 11.0+/-2.9 min, respectively. In four of these rats, also similar to rapid eye movement sleep, the major suppression of genioglossus activity (-74+/-9%) was accompanied by electroencephalogram desynchronization, appearance of hippocampal theta rhythm, and a respiratory rate increase (+ 14+/-3%). In the remaining eight rats, the stereotyped suppression of genioglossus activity (-48+/-3%) occurred without electroencephalogram desynchronization and hippocampal theta, and was accompanied by a respiratory rate decrease (-6+/-2%); a pattern of response typical of decerebrate animals. Within a rat, similar patterns of response to repeated carbachol injections at the same anatomical site were obtained. Pontine atropine prevented responses to subsequent carbachol injections. Thus, in urethane-anaesthetized rats, pontine carbachol consistently produced a differential suppression of pharyngeal versus respiratory pump muscle activity, and in a subset of animals, this was also accompanied by cortical and hippocampal electrographic changes typical of rapid eye movement sleep. This shows that complex and stereotyped neuronal events underlying both ascending and descending signs of rapid eye movement sleep can be pharmacologically activated under general anaesthesia. Such a reduced preparation may be useful for studies into the central neuronal mechanisms underlying generation of rapid eye movement sleep; particularly for studies requiring techniques that are difficult to implement in intact, naturally sleeping animals. The acceleration of the respiratory rate observed only when carbachol induced electroencephalogram desynchronization suggests that neural events associated with electrocortical changes contribute to the respiratory rate increases observed in natural rapid eye movement sleep.

Anesthesia↗
PubMed2003

Intractable epilepsy management: an EEG-oriented approach.

Intractable epilepsy has always posed a challenge to management; conventional, surgical and alternative techniques available so far (e.g., vagal nerve stimulation, i.e. VNS). The author has attempted to search for a novel alternative (drug-regime) approach to its management to minimise any invasive technique or surgery. The drug-regime is based primarily on EEG-background picture (namely synchronisation and de-synchronisation), which the author claims plays a crucial role in epileptogenesis and/or enhancement of epileptic recruitment. Thus an EEG (both in wake and sleep states) shall be a pre-requisite. The novel drug-regime promises to alter the cortical background-activity in a manner to render it un-favorable for epileptogenesis/enhancement of epileptic recruitment, thereby attempting to produce control over Intractable Epilepsy. The new drug-regime, by virtue of its properties to alter the EEG-background activity, thus could enhance the efficacy of conventional treatment and together, they could form a highly effective management for Intractable Epilepsy, thus minimising the intervention of invasive techniques like VNS and epilepsy brain surgery.

Anticonvulsants↗
PubMed2002

Epileptiform spikes desynchronize and diminish fast (gamma) activity of the brain. An "anti-binding" mechanism?

Fast (20-100 Hz) rhythms of electrical activity of the brain have been suggested to be important for perception and cognition providing a mechanism for temporal binding of neural activities underlying mental representations. Also, fast rhythms often precede epileptiform discharges in patients and some experimental models. Generalized slow (2-3 Hz) spike activity after systemic kainic acid (KA) in the rat has been shown to be preceded by intense gamma activity. A relationship between the intensified gamma rhythms and the subsequent spike activity was studied during kainate-induced acute epileptogenesis. Power, multiple coherence and phase were analyzed at frequencies 1-100 Hz in the EEG recorded from the hippocampal-neocortical structures of the rat. Gamma rhythms, extremely intense and highly coherent at the onset of discharges, were followed by a slow rhythm of epileptiform spikes/sharp waves. During this spike activity and immediately afterwards, the gamma power and coherence were significantly decreased. These data show an antagonism between gamma rhythms and spike activity and ability of the latter to desynchronize and suppress the former. They are supportive to the hypothesis that epileptiform spike activity may result from the extreme activation of the "anti-binding" mechanism controlling temporal binding at high frequencies. It is suggested that when fast activity is abnormally intensified, "over-binding" with global synchrony of gamma rhythms can occur in the neural networks. It may lead to inadequate synaptic modifications. To prevent this process, epileptiform discharge develops as a protective mechanism suppressing fast activity. This proposal has implications for our understanding of temporal binding in the brain and how its excessive activation may precipitate the development of pathological states.

Animals↗
PubMed2003

Convulsive and postural effects of lesioning the mid-substantia nigra pars reticulata in naïve and 6-hydroxydopamine lesioned rats.

The subthalamic nucleus is targeted for the treatment of Parkinson's disease. Unilateral lesions improve some aspects of parkinsonism but produce postural abnormalities in animal models but the exact pathways producing these effects remain to be defined. Using a battery of tests we evaluated the effects of lesioning one of the two major subthalamic targets, the substantia nigra pars reticulata in naïve and 6-OHDA lesioned rats. Lesions targeting the mid-substantia nigra pars reticulata resulted in acute tonic-clonic seizures and intense contralateral rotational asymmetry. During the first month after substantia nigra pars reticulata lesions there was normalisation of the ipsilateral head position bias induced by unilateral 6-OHDA lesions, significant contralateral body axis bias but no significant alteration of apomorphine induced rotation and sensorimotor neglect in 6-OHDA lesioned rats. Combined with our previous data, this suggests that subthalamic projections via the substantia nigra pars reticulata are important in seizures and postural behaviours. Therefore unilateral subthalamotomy probably induces postural deficits in hemiparkinsonian animals via projections involving the substantia nigra pars reticulata. This has implications for patients undergoing subthalamotomy for treatment of Parkinson's disease.

Animals↗
PubMed2003

The sciatic nerve of the toad Xenopus laevis as a physiological model of the human cochlear nerve.

The response of single fibres of the human cochlear nerve to electrical stimulation by a cochlear implant has previously been inferred from the response of the cochlear nerve in other mammals. These experiments are hindered by stimulus artefact and the range of stimulus currents used is therefore much less than the perceptual dynamic range (from threshold to discomfort) of human subjects. We have investigated use of the sciatic nerve of the toad Xenopus laevis as a convenient physiological model of the human cochlear nerve. Use of this completely dissected nerve reduces the problems of stimulus artefact whilst maintaining the advantages of a physiological preparation. The validity of the model was assessed by measuring the refractory periods, excitation time-constant, and relative spread of single fibres using microelectrode recording. We have also investigated the response of nerve fibres to sinusoidal stimulation. Based on these measurements, we propose that the sciatic nerve may be a suitable model of the human cochlear nerve if the timescales of stimuli are decreased by a factor of about five to compensate for the slower dynamics of the sciatic nerve and if noise is added to the stimuli to compensate for the lower internal noise of sciatic nerve fibres.

Animals↗
PubMed1986

Central mechanisms of paradoxical sleep.

Paradoxical sleep (PS) is composed of several characteristic "tonic" and "phasic" events. In this paper, it was shown that each of these "PS-subsystems" might be generated by distinct brainstem neuron groups and involved in the cholinergic, cholinoceptive, and monoaminoceptive mechanisms. In addition, it was suggested that the central mechanisms of PS consist of: cholinergic PS-on neurons that discharge tonically and specifically during the periods of PS; and monoaminergic (serotonergic, noradrenergic, and presumably also adrenergic) PS-off neurons that cease firing selectively during this period of sleep. The PS-on neurons play an executive role, while the PS-off ones play a permissive role in the generation of PS. The PS-on neurons are located both in the mediodorsal pontine tegmentum, especially the peri-LC alpha and medial part of the LC alpha, and in the ventromedial medulla, particularly the Mc. The PS-off neurons are located rather diffusely in the lower brainstem. There exist both excitatory interactions between the PS-on neurons, between the PS-off neurons and reciprocal inhibitory interactions between the PS-on and PS-off neurons. Periodically, these interactions lead to, by still unknown mechanisms, the excitation of all PS-on neurons and inhibition of all PS-off neurons, and, consequently, the appearance of PS.

Cholinergic Fibers↗
PubMed1999

Emerging and entraining patterns of the sleep-wake rhythm in preterm and term infants.

It has been repeatedly reported that the sleep-wake rhythm in infants entrains around 3-4 months of age after a transient free-run rhythm. To clarify the emerging and entraining patterns of the sleep-wake rhythm, the sleep and wakefulness of 84 infants (44 preterm and 40 term infants) were longitudinally recorded at home for more than 16 weeks by the day-by-day plot method. Our results showed that the entrained sleep-wake rhythm emerged after transient manifestation of either ultradian or irregular sleep-wake patterns for 3-4 weeks in 75% of the infants. Only 7% of the infants showed a free-running sleep-wake rhythm before the entrainment. These facts suggest that most infants would be entrained to an ordinary daily schedule of mothers without expression of overt free-running rhythm of the biological clock. The mean age of the entrainment was 44.8 postconceptional weeks. There were no significant differences in either frequency of each pattern or the mean age of the entrainment, between preterm and term infants. In conclusion, the entrained sleep-wake rhythm emerges around 1 corrected month, after ultradian patterns in the majority of infants.

Circadian Rhythm↗
PubMedDate not supplied

The double queue method: a numerical method for integrate-and-fire neuron networks.

Numerical methods for initial-value problems based on finite-differencing of differential equations (FDM) are not well suited for the simulation of an integrate-and-fire neuron network (IFNN) due to the discontinuities implied by the firing condition of the neurons. The Double Queue Method (DQM) is an event-queue based numerical method designed for the simulation of an IFNN that can deal with such discontinuities properly. In the DQM, the states of individual neurons at the next predicted discontinuous points are determined by an analytic solution, meaning an optimal performance in both accuracy and speed. A comparison study with the FDM demonstrates the superiority of the DQM, and provides some examples where the FDM gives inaccurate results that can possibly lead to a false conclusion about the dynamics of an IFNN.

Action Potentials↗
PubMedDate not supplied

Distributed synchrony in a cell assembly of spiking neurons.

We investigate the formation of a Hebbian cell assembly of spiking neurons, using a temporal synaptic learning curve that is based on recent experimental findings. It includes potentiation for short time delays between pre- and post-synaptic neuronal spiking, and depression for spiking events occurring in the reverse order. The coupling between the dynamics of synaptic learning and that of neuronal activation leads to interesting results. One possible mode of activity is distributed synchrony, implying spontaneous division of the Hebbian cell assembly into groups, or subassemblies, of cells that fire in a cyclic manner. The behavior of distributed synchrony is investigated both by simulations and by analytic calculations of the resulting synaptic distributions.

Action Potentials↗
PubMedDate not supplied

Associative memory in networks of spiking neurons.

Here, we develop and investigate a computational model of a network of cortical neurons on the base of biophysically well constrained and tested two-compartmental neurons developed by Pinsky and Rinzel [Pinsky, P. F., & Rinzel, J. (1994). Intrinsic and network rhythmogenesis in a reduced Traub model for CA3 neurons. Journal of Computational Neuroscience, 1, 39-60]. To study associative memory, we connect a pool of cells by a structured connectivity matrix. The connection weights are shaped by simple Hebbian coincidence learning using a set of spatially sparse patterns. We study the neuronal activity processes following an external stimulation of a stored memory. In two series of simulation experiments, we explore the effect of different classes of external input, tonic and flashed stimulation. With tonic stimulation, the addressed memory is an attractor of the network dynamics. The memory is displayed rhythmically, coded by phase-locked bursts or regular spikes. The participating neurons have rhythmic activity in the gamma-frequency range (30-80 Hz). If the input is switched from one memory to another, the network activity can follow this change within one or two gamma cycles. Unlike similar models in the literature, we studied the range of high memory capacity (in the order of 0.1 bit/synapse), comparable to optimally tuned formal associative networks. We explored the robustness of efficient retrieval varying the memory load, the excitation/inhibition parameters, and background activity. A stimulation pulse applied to the identical simulation network can push away ongoing network activity and trigger a phase-locked association event within one gamma period. Unlike as under tonic stimulation, the memories are not attractors. After one association process, the network activity moves to other states. Applying in close succession pulses addressing different memories, one can switch through the space of memory patterns. The readout speed can be increased up to the point where in every gamma cycle another pattern is displayed. With pulsed stimulation. bursts become relevant for coding, their occurrence can be used to discriminate relevant processes from background activity.

Action Potentials↗
PubMed2001

Corpus callosum and P300 in schizophrenia.

Functional abnormalities in the interhemispheric transfer via the corpus callosum in schizophrenia may result in filtering problems and information processing problems, which may in turn be related to the synchronization of cortical event-related activity. To explore whether a relationship exists between corpus callosum (CC) size, measured with in-vivo magnetic resonance imaging, and late auditory event-related P300 potentials, 50 patients with schizophrenia as well as 50 healthy controls were examined. The absolute CC size and subregional areas, as well as the CC areas adjusted for total brain volume, were not significantly different between patients with schizophrenia and controls. While no significant group differences were observed for P3a-, P3b-, PSW-amplitudes and P3b-latencies, P3a- and PSW-latencies were significantly prolonged for patients with schizophrenia. Absolute CC total size was significantly correlated with P3b-amplitudes in healthy controls (r=0.29; P=0.044). In patients with schizophrenia, significant correlations were observed between the subregion of the posterior body of the CC and positive slow wave (PSW; r=0.47; P=0.001). P3a-, P3b- and PSW-latencies were not significantly correlated to CC size in either patients with schizophrenia or healthy controls. The results are discussed in terms of the possibility that abnormalities in interhemispheric transfer may underlie the mechanisms of schizophrenia.

Adult↗
PubMed1998

Influence of chronic administration of L-DOPA on event-related desynchronization of mu rhythm preceding voluntary movement in Parkinson's disease.

The spatiotemporal pattern of event-related desynchronization (ERD) during the motor preparation period preceding a self-paced voluntary wrist-flexion was compared in two groups of 10 right and 10 left hemiparkinsonian patients, before and after chronic administration of L-DOPA. ERD was computed in the 9-11 Hz frequency band from 11 source derivations covering the medial frontocentral, central and parietocentral areas, during two successive left and right experimental conditions (100 self-paced wrist flexions). In the two groups ERD appeared with a shorter latency over the contralateral primary sensorimotor area, when the movements were performed with the akinetic hand. After L-DOPA administration, earlier ERD onset before the movement was observed in both groups over the contralateral and ipsilateral central and parietocentral areas. A medial frontocentral ERD distribution was also observed before the onset of movement, especially in the right hemiparkinsonian group. Delayed ERD onset, which shows that programming of movement is affected in Parkinson's disease, may be partially corrected by L-DOPA therapy.

Antiparkinson Agents↗
PubMed1996

Event-related desynchronisation of central beta-rhythms during brisk and slow self-paced finger movements of dominant and nondominant hand.

Changes in central beta-rhythms (14-29 Hz) during movement were investigated in 12 right-handed subjects by quantifying event-related desynchronisation (ERD). EEG was recorded from 24 closely spaced electrodes overlaying the left and right sensorimotor hand area. The subjects performed approximately 80 brisk (movement time < 0.21 s) and 80 slow (movement time 1.3-2.1 s) self-paced extensions of their left or right index finger. Beta-band power attenuation in the preparatory period (2.0-0.5 s before movement onset) was larger in the contralateral hemisphere in both types of movement and similar for both fingers. In the 0.4-s period before the onset of extensor muscle contraction, right-finger movements only showed a significant contralateral preponderance of beta-ERD. During movement an anterior ERD predominance in the right sensorimotor hand area and a widespread ERD in the left sensorimotor area was found for both fingers. The recovery and rebound of beta-rhythms showed contralateral preponderance which was expressed more in the right hemisphere, especially after left-finger movements. The results suggest that the dynamics of premovement desynchronisation and postmovement synchronisation of central beta-rhythms is related to hand dominance.

Adult↗
PubMed1997

Event-related desynchronization in the alpha band and the processing of semantic information.

The hypothesis was tested whether event-related power shifts in the upper alpha band are specifically related to semantic memory processes. In Expt. 1 subjects had to judge whether pairs of sequentially presented words (W1-W2) were semantically congruent. In the following experiments subjects were presented the W1 words of Expt. 1 and were asked to perform a free association task in Expt. 2 and a cued recall task in Expt. 3. It is assumed that semantic memory demands dominate in Expt. 1, whereas working memory demands dominate in Expt. 3 and that Expt. 2 takes an intermediate position with respect to both types of task demands. A significant task-related power change that responds selectively to semantic processing demands was found for the upper alpha band and over the left side of the scalp. The lower alpha band, on the other hand, most likely reflects unspecific processing demands such as attention. A more general interpretation of these findings is that different cognitive processes such as semantic memory, perceptual encoding and attentional processes are reflected by band power changes in different and rather narrow frequency bands over localized regions in the brain.

Adult↗
PubMed2002

Synchrony: a neuronal mechanism for attentional selection?

Attentional selection involves brain processes that select and control the flow of information into the mechanisms that underlie perception and consciousness. One theory proposes that the neural activity that represents the stimuli or events to be attended to is selected through modification of its synchrony. Recent experimental evidence supports this theory, by showing that changes in attentional focus increase the synchrony of neural firing in some neuron pairs and decrease it in others.

Animals↗
PubMed1993

[Spatiotemporal study of event-related desynchronization during self-paced movement].

The desynchronization of Alpha band components during a self-paced movement of the thumb was studied in 7 subjects. The EEG was recorded from 23 electrodes located on the frontocentral, central, and parietocentral regions, referred to the right mastoïde, 4 s before and 2 s after movement onset. The data were then transformed to obtain 11 source derivations. The temporal evolution of the power of the signal within the Alpha band, every 250 ms, associated to the non parametric statistic test of Wilcoxon, authentifies the event-related desynchronization (ERD). The spatiotemporal analysis of ERD underlines on the central regions, two principal locations of ERD: one controlateral to the movement, starting more than 1 s before the movement; the other, ipsilateral, shorter, during the movement. However, no significance desynchronization was underlined on the vertex. The ANOVA used to analyse these results confirms the principal location of ERD on the central region, and seems to indicate a right lateralisation during the right or the left movement.

Adult↗
PubMed1993

[Topographical study of event-related desynchronization: value in the psychophysiologic approach to cognitive processes].

The interest of the event-related desynchronization study has already been evidenced, for example in the study of the cerebral activation modifications consecutive to cognitive processes. We observed here the evolution of this index during a recognition task where the material to memorize varied. Ten young subjects had to learn and then recognize a list of words or forms. The desynchronization of the alpha rhythm consecutive to each stimulus was recorded at 14 localizations on the scalp. We observed that the time evolution of the event-related desynchronization was different in each task. In the visual task, the phenomenon began sooner and was longer lasting. As long as the cortical area were concerned, any dominance nor interhemispheric difference were observed. During the visuospatial recognition task, the event-related desynchronization was however more widespread.

Adolescent↗