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Pentylenetetrazol-induced seizures in immature rats provoke long-term changes in adult hippocampal cholinergic excitability.

PURPOSE: We previously demonstrated that the anticholinesterase eserine provokes interictal-like discharges in the CA3 area of hippocampal slices from rats in which generalized seizures had been induced by pentylenetetrazol (PTZ) when immature. In this study, we investigated several factors as the possible mechanism for this effect, including age at convulsions. METHODS: Rats were injected with PTZ on postnatal day (P) 18-20 or >P60, and neuronal activity was recorded intra- and extracellularly from CA3 5-10 or >40 days later. In additional experiments, convulsions were triggered by kainate or were blocked by pentobarbital. Hippocampal (a) acetylcholine (ACh) innervation density was measured by immunocytochemistry, and ACh and gamma-aminobutyric acid (GABA) contents were determined by high-performance liquid chromatography (HPLC)-electrospray ionization. RESULTS: The excitatory effect of eserine was the most consistent in slices from rats PTZ-treated when immature and after the long interval, whereas the reverse was true in rats treated as adults. This effect was dependent on the occurrence of a seizure and was less prevalent when the seizure had been provoked by kainate. Adult animals PTZ-treated at P20 did not differ from control in (a) poly- or monosynaptic GABAA and GABAB CA3 inhibitory postsynaptic potentials (IPSPs); (b) density of ACh innervation; or (c) tissue content of ACh and GABA. CONCLUSIONS: A PTZ-induced generalized seizure in immature rat provokes endogenous ACh-induced interictal-like discharges in adult hippocampal CA3. This effect is only transiently observed if the seizure was induced in adult. It does not appear to be related to a change in GABAergic inhibition, in density of ACh innervation, or in ACh or GABA content.

Acetylcholine↗

Novel cause of spurious mode switching in dual-chamber pacemakers: atrioventricular desynchronization arrhythmia.

Spurious mode switching is a common problem in DDDR pacing and implantable cardioverter defibrillator systems. It may produce symptoms indistinguishable from classic pacemaker syndrome or paroxysmal atrial arrhythmias due to loss of AV synchrony. The dominant cause of spurious mode switching is oversensing of far-field R waves. This report describes a novel cause of spurious mode switching, AV desynchronization arrhythmia. Clinical manifestations, recognition, and management are discussed.

Arrhythmias, Cardiac↗

Vigilance and evaluation of psychotropic drug effects on EEG.

Dynamics and structure of EEG-patterning are highly sensitive indicators of psychotropic drug effects on the regulation of vigilance. Methodological requirements for an adequate evaluation of these effects and appropriate procedures for their measurement are discussed. The kind of information to be obtained by using these strategies is illustrated by the results of comparative investigations concerning the action of Viloxazine, a new antidepressant drug, on the resting activity and on the waking EEG during performance of various tracking tasks.

Arousal↗

[Perioperative EEG monitoring: studies of the electrophysiological arousal mechanism].

Electroencephalogram recordings have been advocated for assessment of changes in cerebral function during anaesthesia. Controversy exists on the specificity of EEG parameters indicating depth of anaesthesia, because cortical electrical activity is modulated not only by drugs but also by a variety of exogenous and endogenous stimuli. In clinical practice, EEG measures often fail to accurately predict anaesthetic depth since the effects of nociceptive stimulation on the EEG are still not well defined. Previous reports indicate that in anaesthetised patients sensory stimulation may induce a shift to a dominant EEG frequency with faster waves similar to patterns seen during emergence from anaesthesia under certain circumstances. This electrophysiological arousal (EEG desynchronisation) may be associated with clinical arousal phenomena such as movement and increases in haemodynamic and respiratory activity. However, the mechanism of arousal during emergence from anaesthesia may be quite different from arousal reactions induced by noxious stimulation. Recent studies indicate that surgical stimulation can induce increases in slow wave EEG-activity ("reverse" or "paradoxical" arousal) associated with clinical arousal phenomena. Stimulus related delta patterns also were observed after acoustical or painful stimulation in head injured patients. The occurrence of slow EEG wave patterns may be related to functional blockade of the ascending activating system of the brain stem. In contrast, slowing of the EEG is comparable to EEG changes seen with increasing concentrations of anaesthetics. This indicates the difficulty to discriminate arousal phenomena from drug effects using EEG monitoring alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia Recovery Period↗

Controlled test for predictive power of Lyapunov exponents: their inability to predict epileptic seizures.

Lyapunov exponents are a set of fundamental dynamical invariants characterizing a system's sensitive dependence on initial conditions. For more than a decade, it has been claimed that the exponents computed from electroencephalogram (EEG) or electrocorticogram (ECoG) signals can be used for prediction of epileptic seizures minutes or even tens of minutes in advance. The purpose of this paper is to examine the predictive power of Lyapunov exponents. Three approaches are employed. (1) We present qualitative arguments suggesting that the Lyapunov exponents generally are not useful for seizure prediction. (2) We construct a two-dimensional, nonstationary chaotic map with a parameter slowly varying in a range containing a crisis, and test whether this critical event can be predicted by monitoring the evolution of finite-time Lyapunov exponents. This can thus be regarded as a "control test" for the claimed predictive power of the exponents for seizure. We find that two major obstacles arise in this application: statistical fluctuations of the Lyapunov exponents due to finite time computation and noise from the time series. We show that increasing the amount of data in a moving window will not improve the exponents' detective power for characteristic system changes, and that the presence of small noise can ruin completely the predictive power of the exponents. (3) We report negative results obtained from ECoG signals recorded from patients with epilepsy. All these indicate firmly that, the use of Lyapunov exponents for seizure prediction is practically impossible as the brain dynamical system generating the ECoG signals is more complicated than low-dimensional chaotic systems, and is noisy.

Cerebral Cortex↗

Associations of alexithymia with anterior and posterior activation asymmetries during evoked emotions: EEG evidence of right hemisphere "electrocortical effort".

The objective of the study was to examine alexithymia influence on regional cortical activity in nonpatient individuals during evoked emotions. The 62-channels EEG was recorded in non-alexithymic (n = 27) and alexithymic (n = 17) participants viewing emotional film clips. Effects of alexithymia were found in the upper theta, low and upper alpha frequency bands; in all the bands the alexithymics exhibited greater reactivity of the right hemisphere, suggesting enhanced avoidance motivational tendencies, negative affect, and autonomic arousal. Such a right-hemispheric "electrocortical effort" in alexithymia could reflect difficulties in symbolization of emotion resulting from impaired right-hemispheric analogical and global nonverbal emotional representation.

Adolescent↗

Mobile phone effects on children's event-related oscillatory EEG during an auditory memory task.

PURPOSE: To assess the effects of electromagnetic fields (EMF) emitted by mobile phones (MP) on the 1 - 20 Hz event-related brain oscillatory EEG (electroencephalogram) responses in children performing an auditory memory task (encoding and recognition). MATERIALS AND METHODS: EEG data were gathered while 15 subjects (age 10 - 14 years) performed an auditory memory task both with and without exposure to a digital 902 MHz MP in counterbalanced order. RESULTS: During memory encoding, the active MP modulated the event-related desynchronization/synchronization (ERD/ERS) responses in the approximately 4 - 8 Hz EEG frequencies. During recognition, the active MP transformed these brain oscillatory responses in the approximately 4 - 8 Hz and approximately 15 Hz frequencies. CONCLUSIONS: The current findings suggest that EMF emitted by mobile phones has effects on brain oscillatory responses during cognitive processing in children.

Adolescent↗

Neonatal food restriction and binaural ear occlusion interfere with the maturation of cortical motor pyramids in the rat.

Golgi-Cox-impregnated pyramidal neurons of layer five motor cortical area were investigated in control, binaural ear-occluded control, undernourished and binaural ear-occluded undernourished Wistar rats of 12, 20 and 30 days of age. In neonatally undernourished, binaural ear-occluded-undernourished and partly in ear-occluded-control subjects, there were significant reductions in both the number and extent of the distal part of the dendritic branches of motor pyramids compared to their controls. Moreover, minimal effects on perikarya measurements were observed. These findings suggest that neonatal undernutrition and the concurrent reduction of auditory cues affect dendritic arbor development and possibly the convergence of the auditory experience upon motor pyramids and may interfere with the neocortical modulation of postural and movements activities.

Acoustic Stimulation↗

Defective cortical drive to muscle in Parkinson's disease and its improvement with levodopa.

We recorded whole-scalp magnetoencephalographic (MEG) signals simultaneously with surface electromyographic (EMG) activity from eight patients with Parkinson's disease after withdrawal and reinstatement of treatment with levodopa. Variations were seen in the coherence between the forearm extensor EMG and the MEG signal originating near or in the hand region of the primary motor cortex. As a group, the parkinsonian patients withdrawn from levodopa showed a reduction in the coherence at 15-30 Hz and 35-60 Hz, and a further three untreated patients had abnormally strong MEG-EMG coherence at 5-12 Hz compared with when medicated or with eight healthy age-matched control subjects. We conclude that the basal ganglia have a specific effect on the temporal organization of motor cortical activity during voluntary tonic contraction. Abnormalities in this aspect of basal ganglia function may directly contribute to bradykinesia and weakness in Parkinson's disease.

Adult↗

Subthalamic nucleus stimulation modulates motor cortex oscillatory activity in Parkinson's disease.

In Parkinson's disease, impaired motor preparation has been related to an increased latency in the appearance of movement-related desynchronization (MRD) throughout the contralateral primary sensorimotor (PSM) cortex. Internal globus pallidus (GPi) stimulation improved movement desynchronization over the PSM cortex during movement execution but failed to improve impaired motor preparation. PET studies indicate that subthalamic nucleus (STN) stimulation partly reverses the abnormal premotor pattern of brain activation during movement. By monitoring MRD, we aimed to assess changes in premotor and PSM cortex oscillatory activity induced by bilateral STN stimulation and to compare these changes with those induced by l-dopa. Ten Parkinson's disease patients and a group of healthy, age-matched controls performed self-paced wrist flexions in each of four conditions: without either stimulation or l-dopa (the 'off' condition), with stimulation and without l-dopa (On Stim), with l-dopa and without stimulation ('on drug'), and with both stimulation and l-dopa (On Both). Compared with the Off condition, in both the On Stim and the On Drug condition the Unified Parkinson's Disease Rating Scale (UPDRS) III score decreased by about 60% and in the On Both condition it decreased by 80%. The desynchronization latency over central regions contralateral to movement and the movement desynchronization over bilateral central regions were significantly increased by stimulation and by l-dopa, with a maximal effect when the two were associated. Furthermore, desynchronization latency significantly decreased over bilateral frontocentral regions in the three treatment conditions compared with the Off condition. In Parkinson's disease, STN stimulation may induce a change in abnormal cortical oscillatory activity patterns (similar to that produced by l-dopa) by decreasing the abnormal spreading of desynchronization over frontocentral regions and increasing PSM cortex activity during movement preparation and execution, with a correlated improvement in bradykinesia. Parkinsonians under treatment displayed a desynchronization pattern close to that seen in healthy, age-matched controls, although central latencies remained shorter. The study indicates that it is possible to influence cortical reactivity related to the planning and execution of voluntary movement through the basal ganglia, and furthermore that the oscillatory activity of the PSM cortex (in addition to that of premotor areas) could be of major importance in the control of movement-associated, neural activity in Parkinson's disease.

Aged↗

Involvement of human thalamus in the preparation of self-paced movement.

Cortical areas participating in the preparation of voluntary movements have been studied extensively. There is emerging evidence that subcortical structures, particularly the basal ganglia, also contribute to movement preparation. The thalamus is connected to both the basal ganglia and the cerebellar pathways, but its role in movement preparation has not been studied extensively in humans. We studied seven patients who underwent deep brain stimulation (DBS) electrode implantation in the thalamus for treatment of tremor (six patients) and myoclonus-dystonia (one patient). We recorded from the DBS contacts and scalp simultaneously, while patients performed self-paced wrist extension movements. Post-surgical MRI was used for precise localization of the DBS contacts in six patients. Back-averaging of the scalp recordings showed a slow negative movement-related potential (MRP) in all patients (onset 1846 +/- 189 ms prior to electromyography onset), whereas DBS electrode recordings showed pre-movement MRP in five out of seven patients. The thalamic MRP preceded both contralateral and ipsilateral wrist movements. There was no significant difference between the onset time of thalamic MRP (-2116 +/- 607 ms) and cortical MRP. Neither the scalp nor the thalamus showed pre-movement potentials with passive wrist extensions in two patients. In four patients with postoperative MRI who had thalamic MRP, the maximum amplitude or phase reversal occurred at contacts located in the ventral lateral nucleus. Frequency analysis was performed in the five patients with thalamic MRP. The medial frontocentral scalp contacts and the thalamic contacts with maximum MRP amplitude showed two discrete frequency bands in the alpha (mean peak 9 Hz) and beta (mean peak 17 Hz) range. Both frequency bands showed pre-movement event-related desynchronization (ERD). In the grand average, alpha and beta ERD in the scalp and beta ERD in the thalamus began 2.5-2.8 s prior to the onset of movement. However, the thalamic alpha ERD began considerably later, at 1.2 s before EMG onset. The beta band showed cortico-thalamic coherence from the beginning of the baseline period until approximately 0.5 s before the onset of movement. There was no cortico-thalamic coherence in the alpha band. Our findings suggest that the cerebellar thalamus is involved early in the process of movement preparation. Different cortico-subcortical circuits may mediate alpha and beta oscillations. During movement preparation, the motor thalamus and the supplementary motor area predominantly interact in the beta band.

Adult↗

Coherent oscillatory activity in monkey area v4 predicts successful allocation of attention.

Attention serves to select objects from often complex scenes for enhanced processing and perception. In particular, the perception of shape depends critically on attention for integrating the various parts of the selected object into a coherent representation of object shape. To study whether oscillatory neuronal synchrony may serve as a mechanism of attention in shape perception, we introduced a novel shape-tracking task requiring sustained attention to a morphing shape. Attention was found to strongly increase oscillatory currents underlying the recorded field potentials in the gamma-frequency range, thus indicating enhanced neuronal synchrony within the population of V4 neurons representing the attended stimulus. Errors indicating a misdirection of attention to the distracter instead of the target were preceded by a corresponding shift of oscillatory activity from the target's neuronal representation to that of the distracter. No such effect was observed for errors unrelated to attention. Modulations of the attention-dependent enhancement of oscillatory activity occurred in correspondence with changing attentional demands during the course of a trial. The specificity of the effect of attentional errors together with the close coupling between attentional demand and oscillatory activity support the hypothesis that oscillatory neuronal synchrony serves as a mechanism of attention.

Algorithms↗

Waking-sleep modulation of paroxysmal activities induced by partial cortical deafferentation.

We investigated the dependency of electrical seizures produced by cortical undercut upon behavioral states of vigilance in chronically implanted cats. Experiments were performed 1-12 weeks after white matter transection. Multisite field potentials and intracellular activity were recorded from suprasylvian and marginal gyri. Paroxysmal activity developed within days and consisted of spike-wave complexes at 3-4 Hz occurring during the waking state (correlated with eye movements), being enhanced during slow-wave sleep (SWS) and blocked during rapid eye movement (REM) sleep. Prolonged hyperpolarizing events were seen not only during SWS (which is the case in normal animals) but also during both waking and REM, thus resulting in bimodal distribution of the membrane potential in all 3 natural states of vigilance. The increased synchrony of field potential activity expressed by shorter time of propagation over the cortical surface and the tendency toward generalization are ascribed to changes in intrinsic neuronal properties and potential disinhibition following cortical undercut.

Adaptation, Physiological↗

Detection of active and silent states in neocortical neurons from the field potential signal during slow-wave sleep.

Oscillations of the local field potentials (LFPs) or electroencephalogram (EEG) at frequencies below 1 Hz are a hallmark of the slow-wave sleep. However, the timing of the underlying cellular events, which is an alternation of active and silent states of thalamocortical network, can be assessed only approximately from the phase of slow waves. Is it possible to detect, using the LFP or EEG, the timing of each episode of cellular activity or silence? With simultaneous recordings of the LFP and intracellular activity of 2-3 neocortical cells, we show that high-gamma-range (20-100 Hz) components in the LFP have significantly higher power when cortical cells are in active states as compared with silent-state periods. Exploiting this difference we have developed a new method, which uses the LFP signal to detect episodes of activity and silence of neocortical neurons. The method allows robust, reliable, and precise detection of timing of each episode of activity and silence of the neocortical network. It works with both surface and depth EEG, and its performance is affected little by the EEG prefiltering during recording. These results open new perspectives for studying differential operation of neural networks during periods of activity and silence, which rapidly alternate on the subsecond scale.

Action Potentials↗

Hypersynchronous delta sleep EEG activity and sudden arousals from slow-wave sleep in adults without a history of parasomnias: clinical and forensic implications.

STUDY OBJECTIVES: To determine the frequency of classical markers of non-rapid eye movement (NREM) parasomnias--hypersynchronous delta sleep (HSD) electroencephalogram waves and sudden arousals from slow-wave sleep (SWS)--in patients without histories of somnambulism or other NREM parasomnias. DESIGN: Retrospective review. SETTING: Sleep disorders center laboratory. PATIENTS: 82 consecutive patients without a history of parasomnias who underwent diagnostic polysomnograms; 57 men and 25 women, mean age 48+/-13.3 years, were included without regard to diagnosis or findings. All patients had at least 30 seconds of stage 3 or 4 sleep during the polysomnogram. MEASUREMENTS AND RESULTS: The primary diagnosis of all but 4 patients was obstructive sleep apnea (mean respiratory disturbance index, 30 +/- 23.6 [range, 2.7-117] per hour of sleep). Polysomnograms were then reviewed for the presence of HSD and SWS arousals. A total of 235 arousals (mean, 2.9 +/- 2.7; range, 0-14) from stage 3 or 4 sleep were noted. Eight-five percent of all patients had at least 1 SWS arousal and 45% had 3 or more SWS arousals; 85.1% of all arousals from SWS were secondary to sleep-disordered breathing, and 5.9% were secondary to leg movements. At least 1 episode of HSD (mean, 1.4 +/- 1.6; range, 0-9) was noted in 65.8% of patients. CONCLUSIONS: HSD and SWS arousals were a common finding in patients without clinical histories of sleepwalking or other parasomnias but who were found to have frequent respiratory-related arousals during sleep. HSD and SWS arousals thus have a low specificity for NREM parasomnias and, without further research, are not useful for the objective confirmation of parasomnias in clinical evaluations and in the forensic evaluation of sleepwalking as a legal defense.

Arousal↗

Sleep-wake patterns of intact and carotid sinus nerve sectioned rats during hypoxia.

Six male rats breathed 21 an 10% O2 before and after carotid sinus nerve (CSN) section. Polygraphic recording techniques were used to monitor sleep and wakefulness. The effects that these gas mixtures had on the rats' sleep-wake pattern (SWP) were studied. The SWP of CSN sectioned rats breathing 21% O2 was unchanged compared with that of intact rats. While breathing 10% O2, the intact rats' SWP was altered dramatically. Paradoxical sleep (PS) was absent on the first day's exposure to hypoxia. After CSN section, the SWP approximated that of rats in normoxic conditions. The amount of PS increased considerably. It is concluded that the peripheral chemoreceptor reflex pathway contributes, in part, to disruption of the SWP under hypoxic conditions, but not under normoxic conditions. Mechanisms underlying changes in states of consciousness due to hypoxia are discussed.

Animals↗

Isoflurane blunts electroencephalographic and thalamic-reticular formation responses to noxious stimulation in goats.

BACKGROUND: Anesthetics, including isoflurane, depress the electroencephalogram (EEG). Little is known about the quantitative effects of isoflurane on EEG and subcortical electrical activity responses to noxious stimulation. The authors hypothesized that isoflurane would depress the results of EEG and subcortical response to noxious stimulation at concentrations less than those needed to suppress movement. Furthermore, determination of regional differences might aid in elucidation of sites of anesthetic action. METHODS: Ten goats were anesthetized with isoflurane, and minimum alveolar concentration (MAC) was determined using a noxious mechanical stimulus. Depth electrodes were inserted into the midbrain reticular formation and thalamus. Needle electrodes placed in the skull periosteum measured bifrontal and bihemispheric EEG. The noxious stimulus was applied at each of four anesthetic concentrations: 0.6, 0.9, 1.1, and 1.4 MAC. RESULTS: At an isoflurane concentration of 0.6 MAC, the noxious stimulus activated the midbrain reticular formation, thalamic, and bifrontal-hemispheric regions, as shown by decreased high-amplitude, low-frequency power. For all channels combined (mean +/- SD), total (-33+/-7%), delta (-47+/-12%), theta (-23+/-12%), and alpha (-21+/-6%) power decreased after the noxious stimulus (P < 0.001); beta power was unchanged. At 0.9 MAC, total (-35+/-5%), delta (-42+/-7%), theta (-35+/-8%), and alpha (-23+/-11%) power decreased after the noxious stimulus (P < 0.001); beta power was unchanged. At 1.1 MAC only one site, and at 1.4 MAC, no site, had decreased power after the noxious stimulus. CONCLUSIONS: Isoflurane blunted EEG and midbrain reticular formation-thalamus activation response to noxious stimulation at concentrations (1.1 MAC or greater) necessary to prevent movement that occurred after noxious stimulation. It is unknown whether this is a direct effect or an indirect effect via action in the spinal cord.

Anesthesia, Inhalation↗