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Physiological mechanisms of focal epileptogenesis.

The key elements in the development of epileptogenesis appear to be the capacity of membranes in some (pacemaker) neurons to develop intrinsic burst discharges, the presence of disinhibition, and the proper excitatory synaptic circuitry. It is likely that the relative role of each of these processes will differ at different sites in the central nervous system which are prone to epileptogenesis. Synchronization of neuronal populations is a vital element in the development of focal discharge and a variety of mechanisms, including those dependent upon excitatory postsynaptic potentials, and other interactions are possible. Pathological processes may alter some or all of these regulatory mechanisms. However, different pathological entities presumably produce epileptogenesis through different combinations of pathogenetic mechanisms.

Acetylcholine↗

Temporal evolution of oscillations and synchrony in GPi/muscle pairs in Parkinson's disease.

Both standard spectral analysis and time-dependent phase correlation techniques were applied to 27 pairs of tremor-related single units in the globus pallidus internus (GPi) and EMG of patients with Parkinson's disease (PD) undergoing stereotactic neurosurgery. Over long time-scales (approximately 60 s), GPi tremor-related units were statistically coherent with restricted regions of the peripheral musculature displaying tremor. The distribution of pooled coherence across all pairs supports a classification of GPi cell/EMG oscillatory pairs into coherent or noncoherent. Analysis using approximately 2-s sliding windows shows that oscillatory activity in both GPi tremor units and muscles occurs intermittently over time. For brain/muscle pairs that are coherent, there is partial overlap in the times of oscillatory activity but, in most cases, no significant correlation between the times of oscillatory subepisodes in the two signals. Phase locking between coherent pairs occurs transiently; however, the phase delay is similar for different phase-locking subepisodes. Noncoherent pairs also show episodes of transient phase locking, but they occurred less frequently, and no preferred phase delay was seen across subepisodes. Tremor oscillations in pallidum and EMGs are punctuated by phase slips, which were classified as synchronizing or desynchronizing depending on their effect on phase locking. In coherent pairs, the incidence of synchronizing slips is higher than desynchronizing slips, whereas no significant difference was seen for noncoherent pairs. The results of this quantitative characterization of parkinsonian tremor provide a foundation for hypotheses about the structure and dynamical functioning of basal ganglia motor control networks involved in tremor generation.

Action Potentials↗

Multispikes and synchronization in a large neural network with temporal delays.

Coherent rhythms in the gamma frequency range are ubiquitous in the nervous system and thought to be important in a variety of cognitive activities. Such rhythms are known to be able to synchronize with millisecond precision across distances with significant conduction delay; it is mysterious how this can operate in a setting in which cells receive many inputs over a range of time. Here we analyze a version of mechanism, previously proposed, that the synchronization in the CA1 region of the hippocampus depends on the firing of "doublets" by the interneurons. Using a network of local circuits that are arranged in a possibly disordered lattice, we determine the conditions on parameters for existence and stability of synchronous solutions in which the inhibitory interneurons fire single spikes, doublets, or triplets per cycle. We show that the synchronous solution is only marginally stable if the interneurons fire singlets. If they fire doublets, the synchronous state is asymptotically stable in a larger subset of parameter space than if they fire triplets. An unexpected finding is that a small amount of disorder in the lattice structure enlarges the parameter regime in which the doublet solution is stable. Synaptic noise reduces the regime in which the doublet configuration is stable, but only weakly.

Action Potentials↗

Detecting synchronous cell assemblies with limited data and overlapping assemblies.

Two statistical methods-cross-correlation (Moore et al. 1966) and gravity clustering (Gerstein et al. 1985)-were evaluated for their ability to detect synchronous cell assemblies from simulated spike train data. The two methods were first analyzed for their temporal sensitivity to synchronous cell assemblies. The presented approach places a lower bound on the amount of data required to detect a synchronous assembly. On average, both methods required the same minimum amount of recording time to detect significant pairwise correlations, but the gravity method exhibited less variance in the recording time. The precise length of recording depends on the consistency with which a neuron fires synchronously with the assembly but was independent of the assembly firing rate. Next, the statistical methods were tested with respect to their ability to differentiate two distinct assemblies that overlapped in time and space. Both statistics could adequately differentiate two overlapping synchronous assemblies. For cross-correlation, this ability deteriorates quickly when considering three or more simultaneously active, overlapping assemblies, whereas the gravity method should be more flexible in this regard. The work demonstrates the difficulty of detecting assembly phenomena from simultaneous neuronal recordings. Other statistical methods and the detection of other types of assemblies are also discussed.

Action Potentials↗

The effects of memory load on event-related EEG desynchronization and synchronization.

OBJECTIVES: To examine the effects of working memory load on the event-related desynchronization (ERD) and synchronization (ERS) of several narrow EEG frequency bands. METHODS: ERD/ERS responses of the 4-6, 6-8, 8-10 and 10-12 Hz EEG frequency bands were studied in 24 normal subjects performing a visual sequential letter task (so-called n-back task) in which memory load was varied from 0 to 2. RESULTS: In the 4-6 Hz theta frequency band, a long-lasting synchronization was observed in the anterior electrodes, especially after the presentation of targets. In the 6-8 and 8-10 Hz frequency bands, anterior ERS was elicited especially in the 2-back condition (highest memory load). In contrast to the responses of the 8-10 Hz frequency band, in the 10-12 Hz frequency band the 2-back experimental condition elicited the greatest ERD. CONCLUSIONS: In the highest memory load (2-back) experimental condition the attentional capacities were most probably exceeded, resulting in 6-8 and 8-10 Hz ERS. This might reflect an inhibition of such brain areas (frontal cortices) no longer involved in task completion when alternative strategies are needed and utilized. These more 'cognitive' strategies were then reflected as an increase in 10-12 Hz ERD. Additionally, our results support the assumption that the simultaneously recorded ERD/ERS responses of different narrow EEG frequency bands differ and reflect distinct aspects of information processing.

Adult↗

Dynamics of EEG background activity level within quiet sleep in successive cycles in infants.

We investigated in infants the emergence of the trends of the EEG synchronization throughout quiet sleep (QS) as a function of the QS rank. The night sleep of 3 groups with 6 subjects each (aged respectively 9-18 weeks, 21-47 weeks, and 16-45 years) was recorded. A parameter value reflecting the degree of synchronization of the EEG background activity for successive epochs was computed by automatic analysis. For each QS phase 3 indicators of the dynamics of the time course of the EEG parameter activity were determined: the range (difference between the EEG parameter value at the beginning of the QS episode and that at the trough), the trough latency (after QS onset), and the rate of synchronization (range/trough latency). The range and the trough latency increased with age, whereas the rate of synchronization decreased. The range and the rate of synchronization decreased in the successive cycles, whereas the trough latency increased. These results provide further support for the hypothesis of the early emergence of the process S mechanisms and suggest that the framework of the 2-process model could account also for the development of both the EEG background activity dynamics and the sleep-wake organization.

Adolescent↗

Cholecystokinin (CCK-8) elicits prandial sleep in rats.

Electroencephalographic activity and behaviors were recorded in unrestrained adult rats during their first meal and intermeal interval following 17 hrs of food deprivation. Cholecystokinin (CCK-8), in doses of 5, 10, 20, 40, and 80 IDU/kg injected intraperitoneally 10 min after feeding began, suppressed ingestion, elicited and prolonged rest behavior, synchronous wave sleep, and desynchronous wave sleep in a dose-related manner. The 80 IDU/kg dose elicited EEG and behavioral patterns indistinguishable from those of the postprandial control rats. The results suggest that cholecystokinin elicits satiety for food in rats, not illness. The results also suggest that EEG measures can be used to quantify the postprandial state of satiety.

Animals↗

Effect of alcohol on genetically determined variants of the normal electroencephalogram.

The effect of a single dose of alcohol on the electroencephalograms (EEGs) of healthy male carriers of extreme variants of the EEG was examined. The EEG variants included: low voltage, borderline alpha, diffuse beta, and monotonous alpha EEG. The EEGs were analyzed on a small processor by means of a program for interval-amplitude analysis. The synchronizing effect of alcohol (increase of alpha activity and decrease of variance of frequency) was most pronounced in the borderline alpha EEG. As the interindividual variability of the resting EEG is known to be genetically determined, it can be concluded that the differential effects of ethanol on the EEG have a genetic basis.

Adult↗

Synchrony dynamics in monkey V1 predict success in visual detection.

Behavioral measures such as expectancy and attention have been associated with the strength of synchronous neural activity. On this basis, it is hypothesized that synchronous activity affects our ability to detect and recognize visual objects. To investigate the role of synchronous activity in visual perception, we studied the magnitude and precision of correlated activity, before and after stimulus presentation within the visual cortex (V1), in relation to a monkey's performance in a figure-ground discrimination task. We show that during the period of stimulus presentation a transition in synchronized activity occurs that is characterized by a reduction of the correlation peak height and width. Before stimulus onset, broad peak correlations are observed that change towards thin peak correlations after stimulus onset, due to a specific decrease of low-frequency components. The magnitude of the transition in correlated activity is larger, i.e. a stronger desynchronization occurs, when the animal perceives the stimulus correctly than when the animal fails to detect the stimulus. These results therefore show that a transition in synchronous firing is important for the detection of sensory stimuli. We hypothesize that the transition in synchrony reflects a change from loose and global neuronal interactions towards a finer temporal and spatial scale of neuronal interactions, and that such a change in neuronal interactions is required for figure-ground discrimination.

Animals↗

[Effect of clofelin on brain bioelectrical activity].

The hypotensive drug clofelin, 2-(2,6-dichlorphenylamino)-2-imidazoline hydrochloride, which is similar to clonidin exerts a synchronous effect on EEG of cats and rabbits both intravenously and when instilled into the eye conjunctival sac. The synchronous effect of clofelin is reversed by iochimbine, decreased by phentolamine, tropaphen and piroxan, diminished by atropine and benactizin rather than by metacin, and is blocked by amphetamine. The effect of clofelin on the central alpha-adrenoreceptors and certain influence on the central cholinoreactive systems play an essential role in the mechanism of its sedative action.

Adrenergic alpha-Antagonists↗

Aperiodic phase re-setting in scalp EEG of beta-gamma oscillations by state transitions at alpha-theta rates.

We evaluated the rapid changes in regional scalp EEG synchronization in normal subjects with spatial and temporal resolution exceeding prior art 10-fold with a high spatial density array and the Hilbert transform. A curvilinear array of 64 electrodes 3 mm apart extending 18.9 cm across the scalp was used to record EEG at 200/sec. Analytic amplitude (AA) and phase (AP) were calculated at each time step for the 64 traces in the analog pass band of 0.5-120 Hz. AP differences approximated the AP derivative (instantaneous frequency). The AP from unfiltered EEG revealed no reproducible patterns. Filtering was necessary in the beta and gamma ranges according to a technique that optimized the correlation of the AP differences with the activity band pass filtered in the alpha range. The sizes of temporal AP differences were usually within +/-0.5 radian from the average step corresponding to the center frequency of the pass band. Large AP differences were often synchronized over distances of 6 to 19 cm. An optimal pass band to detect and measure these recurring jumps in AP in the beta and gamma ranges was found by maximizing the alpha peak in the cospectrum of the correlation between unfiltered EEG and the band pass AP differences. Synchronized AP jumps recurred in clusters (CAP) at alpha and theta rates in resting subjects and with EMG. Cortex functions by serial changes in state. The Hilbert transform of EEG from high-density arrays can visualize these state transitions with high temporal and spatial resolution and should be useful in relating EEG to cognition.

Alpha Rhythm↗

Cortical and subcortical networks underlying syncopated and synchronized coordination revealed using fMRI. Functional magnetic resonance imaging.

Inherent differences in difficulty between on the beat (synchronization) and off the beat (syncopation) coordination modes are well known. Synchronization is typically quite easy and, once begun, may be carried out with little apparent attention demand. Syncopation tends to be difficult, even though it has been described as a simple, phase-shifted version of a synchronized pattern. We hypothesize that syncopation, unlike synchronization, is organized on a cycle-by-cycle basis, thereby imposing much greater preparatory and attentional demands on the central nervous system. To test this hypothesis we used fMRI to measure the BOLD response during syncopation and synchronization to an auditory stimulus. We found that the distribution of cortical and subcortical areas involved in intentionally coordinating movement with an external metronome depends on the timing pattern employed. Both synchronized and syncopated patterns require activation of contralateral sensorimotor and caudal supplementary motor cortices as well as the (primarily ipsilateral) cerebellum. Moving off the beat, however, requires not only additional activation of the cerebellum but also the recruitment of another network comprised of the basal ganglia, dorsolateral premotor, rostral supplementary motor, prefrontal, and temporal association cortices. No areas were found to be more active during synchronization than syncopation. The functional role of the cortical and subcortical regions areas involved in syncopation supports the hypothesis that whereas synchronization requires little preparation and monitoring, syncopated movements are planned and executed individually on each perception-action cycle.

Acoustic Stimulation↗

Increase in 20-50 Hz (gamma frequencies) power spectrum and synchronization after chronic vagal nerve stimulation.

OBJECTIVE: Though vagus nerve stimulation (VNS) is an important option in pharmaco-resistant epilepsy, its mechanism of action remains unclear. The observation that VNS desynchronised the EEG activity in animals suggested that this mechanism could be involved in VNS antiepileptic effects in humans. Indeed VNS decreases spiking bursts, whereas its effects on the EEG background remain uncertain. The objective of the present study is to investigate how VNS affects local and inter regional syncronization in different frequencies in pharmaco-resistant partial epilepsy. METHODS: Digital recordings acquired in 11 epileptic subjects 1 year and 1 week before VNS surgery were compared with that obtained 1 month and 1 year after VNS activation. Power spectrum and synchronization were then analyzed and compared with an epileptic group of 10 patients treated with AEDs only. RESULTS: VNS decreases the synchronization of theta frequencies (P < 0.01), whereas it increases gamma power spectrum and synchronization (< 0.001 and 0.01, respectively). CONCLUSIONS: The reduction of theta frequencies and the increase in power spectrum and synchronization of gamma bands can be related to VNS anticonvulsant mechanism. In addition, gamma modulation could also play a seizure-independent role in improving attentional performances. SIGNIFICANCE: These results suggest that some antiepileptic mechanisms affected by VNS can be modulated by or be the reflection of EEG changes.

Adult↗

Synchronized brain activity during rehearsal and short-term memory disruption by irrelevant speech is affected by recall mode.

EEG coherence as a measure of synchronization of brain activity was used to investigate effects of irrelevant speech. In a delayed serial recall paradigm 21 healthy participants retained verbal items over a 10-s delay with and without interfering irrelevant speech. Recall after the delay was varied in two modes (spoken vs. written). Behavioral data showed the classic irrelevant speech effect and a superiority of written over spoken recall mode. Coherence, however, was more sensitive to processing characteristics and showed interactions between the irrelevant speech effect and recall mode during the rehearsal delay in theta (4-7.5 Hz), alpha (8-12 Hz), beta (13-20 Hz), and gamma (35-47 Hz) frequency bands. For gamma, a rehearsal-related decrease of the duration of high coherence due to presentation of irrelevant speech was found in a left-lateralized fronto-central and centro-temporal network only in spoken but not in written recall. In theta, coherence at predominantly fronto-parietal electrode combinations was indicative for memory demands and varied with individual working memory capacity assessed by digit span. Alpha coherence revealed similar results and patterns as theta coherence. In beta, a left-hemispheric network showed longer high synchronizations due to irrelevant speech only in written recall mode. EEG results suggest that mode of recall is critical for processing already during the retention period of a delayed serial recall task. Moreover, the finding that different networks are engaged with different recall modes shows that the disrupting effect of irrelevant speech is not a unitary mechanism.

Adolescent↗

Differences in induced brain activity during the performance of learning and working-memory tasks related to intelligence.

Thirteen high intelligent (H-IQ) and 13 low intelligent (L-IQ) individuals solved two figural working-memory (WM) tasks and two figural learning tasks while their EEG was recorded. For the WM tasks, only in the theta band group related differences in induced event-related desynchronization/synchronization (ERD/ERS) were observed. L-IQ individuals displayed greater theta synchronization in the later phases of task completion (1000-2000 ms) as compared to H-IQ individuals. For the learning tasks group related differences in the three alpha bands were observed. In the upper alpha band L-IQ individuals showed greater ERD in the frontal brain areas, whereas H-IQ individuals displayed greater ERD in the parieto-occipital brain areas.

Adult↗

[Effect of serotonin injected into the amygdaloid complex on conditioned and unconditioned alimentary reflexes and electrical brain activity in cats].

The effect of 5-OT injection into the basolateral area of the amygdala complex on conditioned and unconditioned alimentary reflexes and on the concomitant amygdala electrical activity was studied in cats. 5-OT in 100 to 200 mcg doses inhibited the reproduction of conditioned reflexes only, not affecting the unconditioned ones. Under the influence of 5-OT, generation of high-frequency burst activity by the amygdala was blocked; spatial synchronization between the visual and sensorimotor cortex, between the neocortex and the hippocampus was reduced. It is suggested that the basolateral area of the amygdala participates in the organization of conditioned reflexes, and that the serotoninergic system is involved in the neurochemical mechanisms of the inhibitory influence of this structure on the reproduction of conditioned reflexes.

Amygdala↗

Scale-invariant fluctuations of the dynamical synchronization in human brain electrical activity.

The dynamical properties of large-scale, long-term phase synchronization behavior in the alpha range of electroencephalographic signals were investigated. We observed dynamical phase synchronization and presented evidence of an underlying spatiotemporal ordering. Fluctuations in the duration of episodes of intermittent synchrony are scale-invariant. Moreover, the exponent used to describe this behavior is stable across different normal subjects. The results provide a new feature of self-organization in human brain activity and constitute a quantitative basis for modeling its dynamics.

Adolescent↗

Effects of handedness on movement-related changes of central beta rhythms.

The effects of handedness on the movement-related changes in beta rhythms (14-30 Hz) in the left and right perirolandic area were analyzed in 12 right-handed and 11 left-handed subjects. The motor task consisted of unilateral brisk or slow self-paced extension of the right or left index finger. The handedness effects were as follows. First, in both handedness groups, the premovement desynchronization of beta rhythms at both hemispheres was greatest before slow movement of the "nondominant" finger, especially at electrodes presumably overlying the MI areas. Second, the lefthanded group showed less desynchronization in both hemispheres during execution of a slow movement than the righthanded group. Third, the postmovement beta synchronization showed a contralateral preponderance which was greater after movements of the nondominant than the "dominant" finger in the righthanded group and was equal for both fingers in the lefthanded group. The results suggest that handedness effects on movement-related changes in central beta rhythms are coupled to movements of the nondominant finger and that their manifestation differs in the pre- and postmovement periods.

Adult↗