EEG Burst Research Articles

Differential tolerance and cross-tolerance to repeated daily injections of MU and kappa opioid agonists in the rat

This study was designed to compare the development of tolerance to the effects of morphine and ethylketocyclazocine (EKC) on EEG, EEG power spectra and behavior and to assess any cross-tolerance. Adult female Sprague-Dawley rats were implanted with chronic cortical EEG and temporalis muscle EMG recording electrodes and with permanent cannulae in the external jugular vein. In non-tolerant rats, 10 mg/kg (i.v.) injections of morphine and of ethylketocyclazocine produced biphasic EEG and behavioral profiles lasting for 3 and 2 hr, respectively. In both cases, a stuporous phase, associated with high-voltage cortical EEG bursts, was followed by a hyperactive phase, associated with low-voltage desynchronized EEG. However, power spectra derived from epochs of EEG bursting produced by morphine and ethylketocyclazocine were qualitatively different. One group of rats was then given a series of automatic, intravenous injections of morphine, while a second group received ethylketocyclazocine. Following chronic treatment, the duration of the biphasic EEG and behavioral profiles induced by morphine and ethylketocyclazocine were both significantly reduced. In both cases, the intensity of EEG bursting was also reduced as reflected by significant quantitative reductions in EEG power spectral densities. In assessments of cross-tolerance, ethylketocyclazocine tolerant rats were found to be cross-tolerant to the effects of morphine. However, no cross-tolerance to the effects of ethylketocyclazocine in morphine-tolerant rats was observed. These data contribute to a further understanding of the relative heterogeneity of mu and kappa receptor populations and to the differential pharmacodynamics of morphine and ethylketocyclazocine.

Spatial organization of EEGs from olfactory bulb and cortex

This report presents evidence for the concept of ‘wave packet’ (Freeman 1975) in the olfactory system. EEG bursts recorded from electrodes chronically implanted at multiple sites in the olfactory bulb and cortex in awake rabbits were spatially coherent, iso-frequency events. Both bulbar and cortical bursts were composed of a major oscillation in the 35–85 c/sec range. The dominant cortical frequency was within 5% of that of the bulb. A secondary oscillation in the 15–35 c/sec range was found in both bulb and cortex. This was thought to represent a feedback signal of the cortex to the bulb.

Thiopental treatment after global brain ischemia in pigtailed monkeys.

The authors investigated the value of high-dose thiopental (TH) therapy after 16-min complete global brain ischemia (GBI) in three groups of pigtailed monkeys, using a neck cuff model of GBI with 96 h intensive care postischemia (PI). Control group (n18): Normotension was restored within 2 min PI; paralysis/controlled ventilation was maintained for 48 h PI with 50% N2O/O2. Thiopental loading group (n13): Control treatment plus TH-loading with 90 mg/kg iv given from 5 to 65 min PI (mean peak TH plasma level 130 micrograms/ml). Thiopental anesthesia group (n14): Control treatment plus TH anesthesia with 90 mg/kg iv given over 12 h PI (sustained TH plasma levels of 25-35 micrograms/ml and EEG burst suppression). Norepinephrine requirement for blood pressure control PI was greater in the TH groups than in the control group (P less than 0.05). Lidocaine was needed for control of arrhythmias in the TH loading group. There was no significant difference in mortality or neurologic outcome between the groups. At 96 h PI seven of 11 animals were awake in the control group, compared with seven of 12 and six of 12 in the two TH groups. Neurologic deficit scores (NDS) for the survivors at 96 h PI were 23 +/- 6% (mean +/- SD) (n10) in the control group, compared with 25 +/- 9% (n11) and 26 +/- 12% (n10) in the two TH groups (NDS 100% = brain death, 0% = normal). Seizures PI (in 1-2 of each group) were associated with worse neurologic deficits.(ABSTRACT TRUNCATED AT 250 WORDS)

Thiopental bolus during carotid endarterectomy-rational drug therapy?

Ten studies were performed to examine the time course of arterial and venous thiopental concentrations following the administration of thiopental (4 mg X kg-1 over 3 min) for cerebral protection during carotid occlusion in nine patients undergoing elective carotid endarterectomy; in five patients the time course of EEG change was also studied. The arterial and venous thiopental concentrations were similar with no evidence of a sustained arterial-venous gradient. The average arterial concentration was 20.1 microgram X ml-1 +/- 10 (SD) at 2 min after thiopental, and fell rapidly to 13.0 micrograms X ml-1 +/- 3.2 at 5 min, 10.7 micrograms X ml-1 +/- 4.4 at 10 min and 6.2 micrograms X ml-1 at 30 min. After thiopental the EEG record showed an increase in delta activity and in four patients a burst suppression pattern was seen. The duration of burst suppression activity was variable (130 to 367 seconds) but in all instances cortical activity had returned to the pre-thiopental level by five to ten minutes. Thus concentrations of thiopental of 10-30 micrograms X ml-1 were associated with EEG burst suppression and both were seen only within the first five minutes after drug administration. In contrast the carotid artery was occluded for considerably longer (26 +/- 4) minutes. We conclude that, since there was no sustained arterial-venous gradient, either arterial or venous concentrations are adequate for the study of thiopental pharmacokinetics.(ABSTRACT TRUNCATED AT 250 WORDS)

Automatic recognition of epileptic seizures in the EEG

During prolonged EEG monitoring of epileptic patients, the continuous EEG tracing may be replaced by a selective recording of ictal and interictal epileptic activity. We have described previously methods for the EEG recording of seizures with overt clinical manifestations and for the automatic detection of spikes. This paper describes a method for the automatic detection of seizures in the EEG, independently of the presence of clinical signs; it is based on the decomposition of the EEG into elementary waves and the detection of paroxysmal bursts of rhythmic activity having a frequency between 3 and 20 c/sec. Simple procedures are used to measure the amplitude of waves relative to the background, their duration and rhythmicity. The evaluation of the method on 24 surface recordings (average duration 12.4 h) and 44 recordings from intracerebral electrodes (average duration 18.7 h) indicated that it was capable of recognizing numerous types of seizures. False detections due to non-epileptiform rhythmic EEG bursts and to artefacts were quite frequent but were not a serious problem because they did not unduly lengthen the EEG tracing and they could be easily identified by the electroencephalographer. The program can perform on-line and simultaneously the automatic recognition of spikes and of seizures in 16 channels.

Effects of acute δ 9-THC administration on EEG and EEG power spectra in the rat

This study was designed to determine the acute effects of Δ 9-THC on the cortical EEG with the spectral analysis technique. Adult female Sprague-Dawley rats were implanted with chronic cortical and temporalis muscle electrodes. Intraperitoneally administered Δ 9-THC (5 and 10 mg/kgmg/kg) produced a reduction in peak-to-peak voltage of the desynchronized cortical EEG during wakefulness. Associated spectral power was reduced to about 50% of control during the first hour after injection of Δ 9-THC and gradually returned toward the control value over an 8-hr period. Occurrences of Δ 9-THC-induced high-voltage EEG bursts, overriding the reduced EEG tracing, were associated with an EEG spectral peak at 6 Hz. The first few slow-wave sleep (SWS) episodes appearing after Δ 9-THC administration were associated with more slow-frequency waveforms and more slow-frequency spectral power than with control slow-wave sleep episodes. During control rapid eye movement (REM) sleep episodes, an EEG theta wave pattern, with an associated spectral peak at about 8 Hz, was characteristic. Conversely, the first few REM sleep episodes emerging after Δ 9-THC administration contained overriding high-voltage bursts, the related power spectra of which had two peaks at about 7 and 11 Hz.

Use of Anticoagulants, Electroencephalographic Monitoring, and Barbiturate Cerebral Protection in Carotid Endarterectomy

This paper describes a treatment protocol for threatened stroke in patients to carotid endarterectomy. The protocol includes the use of perioperative anticoagulation, intraoperative electroencephalographic (EEG) monitoring, and hypertension or barbiturates to protect the brain against documented ischemia intraoperatively. The rational and methods for protecting the patient from the threat of thromboembolism and cerebral ischemia during each of the periods of specific risk are discussed. The most unique feature of this protocol is the use of thiopental-induced EEG burst suppression for ischemia unresponsive to hypertension during carotid clamping, which has obviated the use of a potentially dangerous and cumbersome in-line arterial shunt.

Use of anticoagulants, electroencephalographic monitoring, and barbiturate cerebral protection in carotid endarterectomy.

This paper describes a treatment protocol for threatened stroke in patients to carotid endarterectomy. The protocol includes the use of perioperative anticoagulation, intraoperative electroencephalographic (EEG) monitoring, and hypertension or barbiturates to protect the brain against documented ischemia intraoperatively. The rational and methods for protecting the patient from the threat of thromboembolism and cerebral ischemia during each of the periods of specific risk are discussed. The most unique feature of this protocol is the use of thiopental-induced EEG burst suppression for ischemia unresponsive to hypertension during carotid clamping, which has obviated the use of a potentially dangerous and cumbersome in-line arterial shunt.

Alterations in cerebral blood flow, oxygen metabolism, and electrical activity produced by high dose sodium thiopental.

High dose barbiturate therapy is being used with increasing frequency in the management of a widening spectrum of neurological disorders. Accurate regulation of the barbiturate dose is essential to maximize cerebral vasoconstriction and reduce brain metabolism while avoiding the cardiovascular depressant side effects of the drug. The purpose of this study was to determine whether the electroencephalogram (EEG) could be used to regulate administration of the agent. In nine mongrel dogs cerebral blood flow (CBF) was determined using the radioactive microsphere technique. After the determination of control CBF, a slow infusion of sodium thiopental was begun. CBF determinations were repeated when the periods of burst suppression in the EEG over several minutes averaged 30, 60, 120, and 240 seconds. CBF and oxygen metabolism showed a nearly identical pattern of a precipituos drop from control levels reaching a plateau at burst suppression between 30 and 60 seconds. Changes in cerebrovascular resistance were of a similar but opposite nature. Significant increases in heart rate occurred with burst suppression of 30 seconds, whereas the arterial pressure and cardiac index decreased with burst suppression between 30 and 60 seconds. In this study cerebral metabolic depression and vasoconstriction from sodium thiopental reached a plateau when sufficient barbiturate was administered to produce EEG burst suppression of between 30 and 60 seconds. At this level there was no important cardiovascular depression. Administration of additional barbiturates significantly decreased systemic arterial pressure and cardiac output, but produced no further decrement in the cerebral metabolic rate of oxygen or the CBF. There was no predictable relationship between cerebral metabolism or cardiovascular function and blood levels of sodium thiopental.

Acute and chronic opiate effects on single units and EEG of medial thalamus and hippocampus: a latency analysis.

Medial thalamic (MT), and hippocampal (HPC) EEG, and single unit activity, and frontal cortical (CTX) EEG were recorded following IV infusions of 0.625 mg morphine/kg in drug-naive, and following 0.0125 mg naloxone/kg in morphine-dependent paralyzed rats. Particular effort was made to assess the latency of the responses in relation to the appearance of high-voltage bursts in the CTX EEG (which has been shown to correlate well with the behavioral state of the animal) and thereby to assess the possible primacy of the effects. In MT, the predominant effect of morphine on units of naive animals was a decrease in activity; that of naloxone in dependent animals, an increase in activity. Morphine decreased theta activity in the MT EEG, while naloxone precipitated theta activity. In the case of morphine, the majority of unit changes preceded CTX EEG changes; in the case of naloxone, most MT unit and EEG changes either coincided with or followed the changed CTX EEG. In contrast, HPC units were relatively unresponsive to morphine, but the HPC EEG often showed marked spiking following the infusion that generally preceded the appearance of spindles in the CTX. Naloxone caused increases and decreases in HPC unit activity, but these changes as well as those of the HPC EEG (also to theta) generally followed corresponding changes in the CTX EEG. The possibility that both areas might be primary sites of action of morphine, but not naloxone, was discussed.

Lack of influence of brain catecholamines on acute effects of barbiturates

Rats with cerebral electrode implants were tested for sensitivity to EEG burst suppression by intravenously-infused sodium methohexital following manipulation of brain catecholamine function. Although depletion of both norepinephrine (NE) and dopamine (DA) with 6-hydroxydopamine resulted in a slight increase in methohexital sensitivity (MHS), similar depletion with α-methyltyrosine did not alter MHS. In addition, desipramine, an agent which selectively blocks uptake of NE did not affect MHS. The results indicate that brain NE and DA exert little, if any, effect on brain responsiveness to the acute effect of barbiturates.

Cerebellar stimulation in alumina-gel monkey model: inverse relationship between clinical seizures and EEG interictal bursts.

The efficacy of cerebellar stimulation was addressed in a chronic monkey model (N = 12) of spontaneous focal motor and secondarily generalized seizures using 24 hr seizure frequency monitoring and all-night EEG recording. The anterior cerebellar vermis was stimulated employing parameters similar to those used in man, 10 Hz, 1 msec pulses, 10 min on, 10 off, at an average current of 2.0 mA. Six weeks pre- and post-base-line periods were compared to a stimulation period of the same length. The results contribute to a clarification of conflicting findings of previous researchers by revealing an inverse relationship between seizure frequency and interictal EEG bursts during the weeks of stimulation. Seizure frequency increased significantly and interictal bursts decreased. Both of these effects (especially the former) were evident in the post-stimulation period, but for different reasons than hypothesized for the period of stimulation. Whereas the therapeutic value of cerebellar stimulation on seizures may be in question, its utilization in the study of mechanisms of epilepsy may be warranted.

Nonlinear dynamics of paleocortex manifested in the olfactory EEG.

The olfactory bulb is the first central component in a highly sensitive yet markedly stable sensory system. It receives a surge of receptor activity with each inspiration and transmits output as a brief burst of oscillatory activity that is most clearly seen in the EEG. These properties together with the known anatomy and physiology of the bulb are used as design criteria to synthesize, evaluate and solve a set of nonlinear differential equations that represent lumped bulbar dynamics. According to the model bulbar processing is in two stages. In the outer layers the interneurons perform the operations of input range compression, integration, clipping, holding, and bias control. In the inner layers the input surge is converted to a burst, which is transmitted by the mitral cells as a pulse density wave. The phase, frequency duration and amplitude of the wave convey information centrally about both the input and the state of the system. The model suffices to replicate the forms of the EEG burst; the pulse probability distributions conditional on the EEG; the waveforms of averaged evoked potentials (AEPs) and post stimulus time (PST) histograms from the bulb and cortex; and the changes in waveform induced by behavioral control of attentiveness and habituation. It is inferred that with selective attention there is a permanent change in the strength of mutually excitatory connections among excitatory neurons, and that with habituation there is a reversible change in the effectiveness of excitatory synapses. The limitations and deficiencies of the model and the need for centrifugal controls of bulbocortical function are discussed.

Evoked and spontaneous corticofugal multiple unit activity during different phases of metrazol infusion in cats

Multiple unit activity (MUA) was recorded from the cerebral peduncle during preictal, ictal and postictal phases of Metrazol infusion in cats. During preictal EEG paroxysmal activity MUA activity increased, sustained MUA discharge preceded the onset of tonic EEG seizure activity and bursts of MUA activity coincided with positive transients during late tonic and clonic periods. No MUA discharge was observed during postictal depression. During preictal periods, Metrazol increased the amplitude and duration of the initial MUA burst to stimulation of the ventralis posterolateralis nucleus. The duration and intensity of the MUA suppression following the response was also increased. The burst-suppression pattern of MUA activity during repetitive stimulation was replaced by a burst-sustained discharge pattern. The changes observed in EEG and MUA are correlated with previously described intracellular changes and provide a consistent picture of EEG, neuronal and axonal behaviour during Metrazol administration. Axonal activity provides a more relevant indication of effective corticofugal activity than does intracellular recording. The level of axonal discharge correlates better with the degree of soma-dendritic depolarization than it does to somatic spike generation.

Polygraphic sleep studies in subacute sclerosing panencephalitis

As a measure of the brain's homeostatic functions quantitative analysis of sleep cycles and stages may show more reliably than clinical-neurological investigations changes or progression in the course of generalized central nervous disease. This technique was applied to study the course of SSPE and to provide a neurological parameter in a therapeutic trial with lymphocyte transfer factor. Whole night polygraphic recordings were done in 12 patients with SSPE before and after transfer factor repeatedly over 4 weeks to 1 year. The normal pattern of REM- and NREM-sleep disappeared early in the course of the disease. Disappearance of rapid eye movements showed involvement of mesencephalic pontine structures, absence of sleep spindles thalamic alteration. In 10 patients two alternating states remained, discernible by EEG pattern, heart rate, degree of jerking and degree of correlation between EEG bursts, respiratory phase and heart rate Alternation of these 2 patterns became increasingly rapid and irregular in fast deteriorating cases and were extremely slow in more chronic cases. No cyclic changes were seen in one peracute and in one “burnt out” case. Application of transfer factor had no effect on the deterioration of sleep cycle organization.

Immediate effects of total visual deafferentation on single unit activity in the visual cortex of freely behaving cats. II. Rhythmic EEG bursts and PGO waves.

Temporal correlations between single unit activity and phasic EEG waves in wakefulness and deep (REM) sleep were studied in the visual cortex (VC) of totally visually deafferented cats. In wakefulness single unit activity was either enhanced (41 units, 42.3%), suppressed (10 units, 10.3%) or unchanged (46 units, 47.4%) during high-amplitude slow wave bursts (6–8/sec) in the background EEG. The nature of “rhythmic” firing was common for both types of units which either increased or decreased discharge rates during this slow wave bursts. This rhythmic short-lasting synchronization in wakefulness was interpreted as an evidence of enhanced, synchronization in deafferented VC neurons. In deep sleep various relationships were observed between single unit activity and ponto-geniculo-occipital (PGO) waves following deafferentation including both excitatory (25 units, 29.7%) and, in contrast to intact animals, inhibitory (17 units, 20.2%) correlations. The remaining half (42 of 84 units) showed no obvious correlation with PGO waves. Six of 25 units which were activated by PGO waves started to fire immediately after the onset of PGO waves. Eleven of 17 suppressed units stopped to fire immediately after the onset of PGO waves. These units with close excitatory or inhibitory phase relation to PGO waves had extremely high discharge rates. The contrasting relationship of striate and nonstriate units to PGO waves seen in the intact VC waned after total visual deafferentation. Possible mechanisms for inhibitory influences of PGO waves on deafferented VC units were discussed.

EEG correlates of behavior in the cat. I. Pattern discrimination and its alteration by atropine and LSD-25

1. 1. Electrophysiological changes associated with the acquisition and retention of two visual pattern tasks in cats were found principally in the visual system (lateral geniculate and the visual area of the lateral gyrus), the midbrain reticular formation and the anterior ventral nucleus of the thalamus. 2. 2. A comparison of EEG correlates of acquisition of the two behaviors failed to reveal consistent differences. Instead, a parallel, gradual development of evoked responses during initial training occurred. During overtraining, in the single pattern there was a diminution of evoked activity; however, this was not marked in the two pattern situation. 3. 3. Atropine sulfate was found to increase latency or abolish response in a single pattern discrimination task. In a two pattern discrimination task, atropine increased response latency, caused errors of commission, and finally blocked responding in a dose related sequence. The drug effects were related to central rather than peripheral action as demonstrated by the lack of effect of atropine methylnitrate under the same conditions. The behavioral deficits were accompanied by slow waves and high voltage bursts in the spontaneous EEG from neocortical, hippocampal and subcortical areas, while the evoked responses to the conditioning stimulus during the trials were delayed in onset and increased in amplitude in the visual system as compared to the pre-drug trials. 4. 4. The effects of LSD-25 were characterized by errors of commission in both behavioral tasks. The behavioral alterations were associated with rhythmic slow wave bursts in the spontaneous EEG from neocortical and subcortical areas, and the evoked responses to the conditioning stimulus during correct trials were increased in the visual system. 5. 5. Differences in evoked responses between correct and incorrect trials were striking in the single but not in the two pattern task, but error trials were not different under either drug from controls.

The correlation of pain relief, neurological sign, EEG and anatomical lesion sites in pain patients treated by stereotaxic thalamotomy.

SummaryThe clinical syndromes are described on the basis of an anatomical correlation in nine patients who have had stereotaxic thalamotomy for the relief of intractable pain. The cases who have bilateral lesions in the ventroposterior parts of CEM get excellent pain relief without any kind of serious complication. The case who has lesions in the VPM is characterized by sensory loss with temporary pain relief. However, bilateral lesion group is characterized by psychiatric syndrome and slow wave bursts in EEG. The Pf‐pretectal lesion group has serious complications which include unconsciousness, extrapyramidal motor effect and slow wave bursts in EEG.This result indicates that the ventroposterior parts of CEM have an important role in perceiving pain sensation but have not chief role in maintaining consciousness and altering EEG. To make lesion of the bilateral CEM is most suitable operation in order to relief of intractable pain caused by malignant tumor.

Unit activity in the hypothalamus of the cat: effect of genital stimuli, luteinizing hormone and oxytocin.

The activity of single neurones in the hypothalamus of ovariectomized estrogen-treated cats immobilized by gallamine triethiodide was recorded by means of steel microelectrodes with simultaneous observation of presigmoidal EEG. Alterations in the firing rates of single units were analyzed during and after vaginal stimulation during anestrus and estrus animal. Unit responses to LH (3 Armour units) and oxytocin (0.3 U.) injection were also observed both at the anestrous and estrous states.1. In the VMH of the hypothalamus, neurones were found which responded to LH administration by a long lasting decrease in unit firing rate with latency of 10-20 minutes in estrus and anestrus. Some ARC neurones showed an increase during estrus, and also an increase to a less degree in anestrus. Also, in the AHA some neurones were found which increased in discharge rate, but the change was less remarkable. The changes in the LHA or the PHY neurones were not clear.2. Oxytocin sensitive neurones discrete from LH sensitive neurones were found in the hypothalamus. The unit discharge rate increased or decreased with latency of 40-80 seconds lasting for several minutes according to electrode location and to the phase of the sexual cycle.The VMH neuronal activity showed a slight facilitation in estrus but a strong inhibition in anestrus. In the ventromedial part of the LHA and the AHA the unitary activity was inhibited by oxytocin during estrus, but facilitated in anestrus. Distribution of LHA responsive neurones in the dorsolateral portion of LHA was quite disperse.3. The VMH neurones discharged in accordance with the change in presigmoidal EEG pattern. During vaginal stimulation in estrus the VMH neural. activity was inhibited or unchanged but after cessation of the stimulation it showed a transient facilitation with simultaneous appearance of spindle bursts. in presigmoidal EEG. A marked inhibition followed which lasted for more than 20 minutes, with cortical EEG spindle bursts intermingled with arousal waves.Some AHA neurones in estrus showed a marked facilitation during vaginal stimulation, but no after-reaction was observed.Most neurones in the ventromedial part of the LHA, both in estrus and anestrus, showed increased firing activity during vaginal stimulation. After the cessation of stimulation the activity began to decline simultaneously with the appearance of spindle bursts in the presigmoidal EEG, and after about 10 minutes the initial state was restored. Long-term alteration, such as that seen in the VMH, was not observed.During estrus the neurones in the dorsolateral part of the LHA showed a transient increase in discharge activity after vaginal stimulation independent of the changes in presigmoidal EEG activity. In anestrus these neurones did not respond to vaginal stimulation.Stimulation by other means such as pinching or touching, had an effect similar to vaginal stimulation, except that no after-reaction occurred.

EFFECTS OF BARBITURATES AND ETHER ON SPONTANEOUS ELECTRICAL ACTIVITY OF DOG BRAIN

EFFECTS OF BARBITURATES AND ETHER ON SPONTANEOUS ELECTRICAL ACTIVITY OF DOG BRAIN