Neocortical EEG Research Articles

The effects of concurrent manipulations of cholinergic and noradrenergic systems on neocortical EEG and spatial learning

In the spatial learning test, young animals were divided into three groups receiving saline, scopolamine (0.15 mg/kg), or scopolamine (0.8 mg/kg). Half of the animals in each group were lesioned with DSP-4 to destroy noradrenergic fibers. DSP-4 lesions did not produce any significant impairment alone or in combination with a lower dose of scopolamine (0.15 mg/kg), but they did further augment the scopolamine (0.8 mg/kg)-induced defect. In the electroencephalography (EEG) experiment, both control rats and DSP-4-lesioned rats were recorded after receiving saline, scopolamine (0.15 mg/kg), and scopolamine (0.8 mg/kg) injections. Scopolamine induced a dose- and behavioral state-dependent EEG slowing, whereas DSP-4 lesions did not change either baseline EEG activity or EEG reactivity to scopolamine.

Brain amines and neocortical EEG in young and aged rats

1. Frontal and parieto-occipital electroencephalography (EEG) of young (4 months-old) and aged (17 and 22 months-old) Wistar rats were analyzed, both during movement and during waking immobility. 2. The levels of monoamines, serotonin and their metabolites were measured from the frontal cortex, parieto-occipital cortex, hippocampus, brainstem and midbrain. 3. In aged rats, as compared to young rats, the most apparent changes of the quantitative EEG spectrum were the decreased amplitude of alpha (5–10 Hz) and beta (10–20 Hz) frequency bands in the frontal and parieto-occipital cortices during both movement and waking immobility behavior ( p < 0.05). 4. The levels of dopamine (DA), homovanillinic acid (HVA), serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) or the ratios of 5-HT/5-HIAA and DA/HVA did not differ between young and aged rats in any brain region studied, with the exceptions of brainstem DA and parieto-occipital 5-HIAA, which were elevated in aged rats ( p < 0.05). 5. In the frontal cortex, hippocampus and midbrain, noradrenaline (NA) levels of aged rats were slightly increased as compared to young rats ( p < 0.05). 6. NA levels of the parieto-occipital cortex and brainstem did not change during aging. 7. Furthermore, there were no clear correlations between the decreased amplitude of the quantitative EEG spectrum and monoamine or serotonin concentrations, or the ratios of 5-HT/5-HIAA and DA/HVA in the cerebral cortex of aging Wistar rat. 8. These results established that the slowing of the neocortical EEG during aging of rat may occur without concomitant degeneration of noradrenergic, dopaminergic or serotonergic systems which supposedly have at least some role in the regulation of neocortical EEG.

Multisite recording of brain field potentials and unit activity in freely moving rats

A technique has been developed to record from 16 different brain sites of the freely moving rat using subminiature MOSFET preamplifiers. The high input impedance, small size, durability and light weight of the amplifiers and connecting cable allows high quality multisite recording of field potentials and unit activity. In addition, a movable headstage for positioning multiple microelectrodes is described. The compact recording system permits one to construct neocortical EEG maps, instant depth profiles of evoked and spontaneous field data, and to study neuronal synchrony of distant cell populations.

Nucleus basalis and thalamic control of neocortical activity in the freely moving rat

EEG and single-unit techniques have been used to study the EEG correlates of cellular firing in the neocortex, n. reticularis (RT) and "specific" thalamic nuclei, and the cholinergic forebrain area (nucleus basalis, NB). Neuronal firing was related to the ongoing behavior of the rat. In addition, using a 16-channel neocortical recording/mapping system, we studied the effects of ibotenic acid lesion of NB, RT, and other thalamic nuclei on the patterns and spatial distribution of neocortical electrical activity. The majority of neurons in neocortex, NB, and RT increased their firing rates during walking, as compared to during immobility, with concurrent decrease of delta power in the neocortical EEG. During immobility, high-voltage spindles (HVS; greater than 1 mV) were occasionally recorded from the neocortex. Depth profiles of HVS and slow delta waves were different in the neocortex. Neocortical cells decreased their discharge frequency during the positive portion of delta waves recorded in layers V and VI. All cells in the neocortex and specific thalamic nuclei fired rhythmically and phase-locked to the spike component of HVS. RT neurons showed an opposite phase relationship and fired mainly during the wave component of HVS. Half of the NB neurons also showed phasic modulation with HVS. Circumscribed lesion of RT and extensive damage of other thalamic regions, including the intralaminar nuclei, suppressed HVS but had no effect on the neocortical EEG correlates of behavior. In sharp contrast, damage to the NB resulted in a dramatic increase of slow delta waves on the side of the lesion, mimicking the effect of scopolamine administration. We suggest that the NB plays a key role in neocortical arousal by directly activating the neocortex and by suppressing the rhythm generation in the RT-thalamocortical circuitry. We further suggest that the NB system may serve as a structural basis for the concept of the generalized ascending activation of Moruzzi and Magoun (1949).

Etude electrophysiologique de la tianeptine, nouveau stimulant du recaptage de la serotonine possedant une activite antidepressive

Tianeptine is a clinically effective antidepressant, not chemically related to classical tricyclic compounds. Its mechanism of action preferentially involves central serotoninergic transmissions, by increasing uptake after acute and chronic administration in rat brain and platelets and in human platelets. We studied the effects of tianeptine on three currently used electrophysiological methods: Ro4-1284 induced PGO waves in the cat, neocortical EEG activity in the acute rat preparation and sleep-wakefulness modifications in chronically implanted rats. Density of Ro4-1284 induced PGO waves was reduced by tianeptine, the minimal effective dose being 2 mg.kg-1i.v. (ED50 = 2.9 mg.kg-1i.v.). In acute rat preparation, the low voltage fast waves basal EEG pattern was not modified by tianeptine in a dose range of 1.25 to 20 mg.kg-1i.p. Higher dosage (25 mg.kg-1i.p.) induced high amplitude episodes with few or no delta waves. Low doses which did not apparently modify acute EEG have been tested on sleep-wakefulness cycle in implanted rats. Tianeptine, after single administration, did not modify sleep states up to 2.5 mg.kg-1i.p. An increased wakefulness was observed during the first hour after 5-10 mg.kg-1i.p., afterwards sleep states returned to control values up to 12 h. A subsequent 12 h recording performed 24 h after treatment did not show any change compared to pretreatment baseline. After sub-chronic administration (2.5 mg.kg-1i.p./day, 9 days) no change was observed in sleepwake pattern during or after cessation of treatment. Tianeptine EEG profile is radically different from those usually induced by classical tricyclic antidepressants.

Transient neocortical, hippocampal and amygdaloid EEG silence induced by one minute inhalation of high concentration CO2 in swine.

The study is part of a series of investigations performed with the ultimate goal of obtaining an objective evaluation of the ethical aspects and the narcotic efficiency of CO2 inhalation used as pre-slaughter anaesthesia for swine. Six Yorkshire swine were exposed twice to 80% CO2 for 1 min during simultaneous recording of the EEGs from the frontal neocortex, the dorsal hippocampus, and the amygdaloid region via permanently implanted electrodes. In five of the animals myoclonic jerks started at 28 +/- 1 s of CO2 exposure and lasted for 6 +/- 2 s. Neocortical slow wave (delta) activity and increased amplitude of the hippocampal theta (5-7 Hz) waves (i.e. EEG changes seen during the second stage of barbiturate anaesthesia) had developed before the brief period of myoclonic jerks. After this period the EEG activity gradually declined, resulting in neocortical EEG silence at the end of the exposure. This apparent isoelectricity lasted for on average 1 min. The return of the neocortical EEG activity exhibited a pattern reverse to its disappearance, but was much prolonged in comparison to the EEG extinction. Pre-exposure neocortical EEG pattern was not regained until 3-5 min post-exposure. In eight out of 11 experiments the CO2 inhalation also induced hippocampal EEG silence lasting for on average 30 s. EEG flattening was further obtained when recording from the amygdaloid nuclear complex and the adjacent pyriform cortex. The observed changes in the neocortical and hippocampal EEGs suggest that the present swine were unconscious already when they exhibited motor reactions. This does not exclude the possibility that CO2-independent stress/arousal factors present in a slaughterhouse environment may facilitate the development of motor phenomena similar to seizures, with the result that such reactions become manifest before the neocortical EEG exhibits an anaesthesia pattern. The duration of the observed EEG silence implies that, from the ethical point of view, exsanguination might safely be performed within 1 min after the moment when the animal is removed from the high concentration CO2. However, the slow return to a pre-exposure neocortical EEG pattern suggests that the swine remains unconscious for at least another minute.

A spindle-like wave in the cat hippocampus: a novel vigilance level-dependent electrical activity

Bursts of spindle-like waves of about 110 Hz (minispindle) were recorded from the cat hippocampus. The minispindle began to appear in parallel with the slowing of neocortical EEG and occurred most frequently during the deep slow-wave sleep episode. The minispindles could be recorded simultaneously at different points not only in the ipsilateral but also in the contralateral hippocampus with a time lag less than 30 ms.

Neural mechanisms distinguishing the neocortical EEG of C57BL/6 mice from that of DBA/2 mice

C57BL/6 inbred mice lack the 1–5 sec bursts of 6–7 cps spindles characteristic of the neocortical EEG of DBA/2 mice during waking. C57BL/6 mice 1. (1) may be unable to generate any synchronized cortical EEG activity 2. (2) may lack the thalamocortical circuitry required to generate these brief spindle episodes (BSEs) 3. (3) may lack mechanisms that can activate this circuitry 4. (4) may possess a potent mechanism to suppress BSE initiation and generation. Possibilities 1 and 2 have been eliminated because C57BL/6 mice generate pentobarbital, rostropontine-induced and sleep spindles, and because certain C57BL/6 sleep spindles resembled the BSEs seen in DBA/2 mice. Possibilities 3 and 4 were examined in the experiments reported here. In DBA/2 mice, pentylenetetrazol activates BSEs at subconvulsant doses. In contrast, neither 20 nor 50 mg/kg, IP, pentylenetetrazol activated BSEs in C57BL/6 mice, although the higher dose provoked 4–5 cps slow waves and myoclonic jerks. In DBA/2 mice, the beta-noradrenergic antagonist propranolol has been reported to powerfully release BSEs. In C57BL/6 mice, 10 and 15 mg/kg propanolol weakly released BSEs: fewer than 3 per hour occurred. Hence neither possibilities 3 and 4 are sufficient in themselves to explain the lack of BSEs during waking in C57BL/6 mice. However, simultaneous administration of 10 mg/kg propranolol and 20 mg/kg pentylenetetrazol provoked numerous BSEs in C57BL/6 mice. This suggests that perhaps C57BL/6 mice, as compared to DBA/2 mice, possess both a more powerful noradrenergic mechanism to suppress spindles and a more weakly functioning mechanism to activate BSEs. Hence possibilities 3 and 4 may both be correct. The Fl offspring of a cross between C57BL/6 and DBA/2 mice resembled the DBA/2 parents in that pentylenetetrazol (30 mg/kg, IP) strongly provoked BSEs in every Fl mouse. Hence this electroencephalographic trait may show a dominant inheritance.

Electrocortical activity patterns during chloral hydrate induced sleep in developing rats

The neocortical EEG was quantified during sleep, while under light chloral hydrate anaesthesia, in rats ranging from 9 to 20 days of postnatal age. Continuous amplitude modulation at 0.5–1.0 min per cycle, synchronously over all frequency bands, was observed in 9- and in 10-day-old pups. By day 13, the mean amplitude had risen considerably in each of the frequency bands, and a slow fluctuation in delta-wave activity began to be discernible. Sodium glutamate injections induced EEG changes at 10 days which mimicked certain aspects of normal maturation (viz., large stereotyped potentials at irregular intervals, along with a selective increase in delta-wave activity). Natural as well as experimentally induced EEG changes were paralleled by a rise in neocortical amino acid concentrations, including glutamic acid and GABA. Delta wave amplitudes during quiet sleep increased still further between 13 and 14 days, while beta activity remained at a constant level. Between days 14 and 15 a precipitous decline in delta-wave activity was found, attributable to greater inhibition of slow waves during active sleep. No further developmental changes were noted, except for a gradual rise in the time spent in quiet sleep relative to active sleep.

STIMULANT AND DEPRESSANT EFFECTS OF KETAMINE ON NEOCORTICAL ACTIVITY IN CATS

Electroencephalographic (EEG) and behavioural effects of ketamine were examined in chronically-prepared cats carrying recording electrodes for neocortical EEG and a stimulating electrode in the optic chiasma for producing evoked potentials. Ketamine 3-5 mg kg-1 alone acted as a stimulant upon the cortical electrical activity with induced immobility. However, when ketamine was given in combination with barbiturate, it appeared to be a depressant in the sense that the anaesthetic effect of barbiturate was potentiated. Ketamine also failed to excite the neocortex of cats whose mesencephalic reticular formation had been destroyed. These results suggest that ketamine, administered in cats with no pretreatment or lesion, enhanced the neocortical activity via the ascending reticular activating system of the brain stem.

Nucleus locus ceruleus: new evidence of anatomical and physiological specificity.

Nucleus locus ceruleus: new evidence of anatomical and physiological specificity.

Spectral analysis of neocortical and hippocampal EEG in the protein malnourished rat

In these studies, power spectral analysis techniques were utilized to quantify changes in the cortical and hippocampal EEG obtained from rats reared on either an 8% or 25% casein diet as they mature from 14 to 22 days of age. Analyses of the power spectral data obtained from the frontal cortex of rats reared on the 25% casein diet during this preweaning period (14–22 days) indicated increases in the power in the 0.5–3.5 c/sec frequency band primarily during slow-wave sleep. Prenatal protein malnutrition (8% casein diet) significantly reduced the low frequency power content in the cortical EEG obtained during slow-wave sleep at 18 and 22 days of age. Analyses of power spectral data obtained from the hippocampal EEG during REM sleep also revealed developmental and diet-related differences. The frequency at which the peak power occurs in the theta band (4–11 c/sec) was found to increase normally in a linear fashion from 14 to 22 days of age (from 4.4 to 5.5 c/sec) in rats reared on the 25% casein diet. In addition, power in the 4–7 c/sec band significantly increased during this preweaning period. Prenatal protein malnutrition significantly slowed the development of theta frequency and produced higher values of power in the component of theta rhythm. Finally, vigilance profiles showed that rats normally progress from 14 days of age when REM sleep dominates their vigilance profile, to 22 days of age when they spend significantly more time in slow-wave sleep. Prenatal protein malnutrition retards this normal developmental sequence by significantly reducing the REM sleep time at 14 and 18 days of age and increasing the time spend in aroused waking at both these ages. However, at the time of weaning, i.e., at 22 days of age, these differences in sleep-waking behavior were no longer observed to be significant.

Slow rhythmic oscillations of EEG slow-wave amplitudes and their relations to midbrain reticular discharge

The amplitude of anterior neocortical EEG slow-waves (0.5–4Hz) measured during quiet waking, drowsy (WS) and synchronized sleep (S) states showed slow rhythmic oscillations in WS and S similar to those previously reported in midbrain reticular neurons (periods of 8–12 s). Abrupt changes in slow rhythms of unit discharge was reflected by similar changes in the amplitude of EEG slow-waves. Analyses on grouped data from many WS → S transitions showed no common phase relation between oscillations of EEG slow-wave amplitudes prior to S onset, but showed signs of a common phase relationship after. These findings, together with a significantly lower EEG synchronization level just before S onset in grouped data, suggest that the beginning of S is phase-related to oscillations of slow-wave amplitudes in WS.

An assessment of the state hypothesis of animal ‘hypnosis’ through an analysis of neocortical and hippocampal EEG in spontaneously immobile and hypnotized rabbits

Hippocampal and neocortical EEG was studied in spontaneously immobile rabbits and in immobilized rabbits, ‘animal hypnosis.’ Neocortical low voltage fast activity (LVFA) and hippocampal rhythmical slow activity (RSA) occurred spontaneously and were elicited by sensory stimulation, eserine and brain stimulation in normally immobile and hypnotized animals. Atropine sulfate blocked the LVFA and RSA that occurred during spontaneous immobility and hypnosis but not the LVFA and RSA that occurred during movement. RSA was also recorded from both CA1 and dentate gyrus generators of the hippocampus during both types of immobility. The results show that hypnotized rabbits have the same type II (atropine-sensitive) EEG that is found in spontaneously immobile rabbits. The presence of type II EEG during hypnosis and its sustained sensitivity to stimulation is compatible with the view that the EEG activity is not uncoupled from its normal behavioral correlates. Perhaps normal EEG during animal hypnosis allows normal sensorimotor functions. This may permit the possibility of escape from predators at opportune moments once the immobility has served its defensive function.

Electric Fields of the Brain: The Neurophysics of EEG

1. The physics-EEG interface 2. Fallacies in EEG 3. An overview of electromagnetic fields 4. Electric fields and currents in biological tissue 5. Current sources in a homogeneous and isotropic medium 6. Current sources in inhomogeneous and isotropic media 7. Recording strategies, reference issues, and dipole localization 8. High-resolution EEG 9. Measures of EEG dynamic properties 10. Spatial-temporal properties of EEG 11. Neocortical dynamics, EEG, and cognition APPENDICES A. Introduction to the calculus of vector fields B. Quasi-static reduction of Maxwell's equations C. Surface magnetic field due to a dipole at an arbitrary location in a volume conductor D. Derivation of the membrane diffusion equation E. Solutions to the membrane diffusion equation F. Point source in a five layered plane medium G. Radial dipole and dipole layer inside the 4-sphere model H. Tangential dipole inside concentric spherical shells I. Spherical harmonics J. The spline Laplacian K. Impressed currents and cross-scale relations in volume conductors L. Outline of neocortical dynamic global theory

Associative and non-associative changes in unit activity of the rat hippocampus

Two main types of neurons of the dorsal hippocampus were recorded in chronic rats during the classical conditioning of an arousal phenomenon (neocortical EEG desynchrony). The relative importance of the associative and non-associative factors was assessed by a differentiation procedure. In naive rats, during the “acquisition” session most type-I neurons rapidly acquired an “inhibitory” response closely parallel to the EEG response. Neither of these responses showed differentiation. Some type-II neurons acquired an “excitatory” response which was independent of the EEG response and which had a significant tendency to differentiation. These data were confirmed in rats submitted to several “retention” sessions. All the type-I neurons were undifferentiated while 11 out of 41 type-II neurons were differentiated. Type-I neurons were characterized by a bursting mode of discharge. Their activity was higher during slow wave sleep (SWS) than during wakefulness (W) or paradoxical sleep (PS). Most of the differentiated type-II neurons were more active during W and/or PS than during SWS.

Inhibitory action of the combination of aminopyrine and secobarbital on EEG activation, neocortical recruiting and augmenting responses in rabbits.

The effect of the combination of aminopyrine and secobarbital at a molar ratio of 2:1, the mixture and molecular compound, on rabbit EEG activation was examined. Secobarbital 40 mg/kg p.o. elevated threshold voltages in the neocortical and hippocampal EEG activation by high frequency electrical stimulation of the midbrain reticular formation (MRF), nucleus centralis medialis (CM) of the thalamus, and posterior hypothalamus (PHA) by 40, 40 and 80% respectively. Aminopyrine 80 mg/kg p.o. alone did not affect the arousal responses. The molecular compound 120 mg/kg p.o. has more potent and long-lasting actions in inhibiting the arousal responses induced by the stimulation of MRF (80%) and CM (50%) than with secobarbital alone. The inhibitory action of the mixture 120 mg/kg p.o. on the PHA-arousal response (40%) was significantly weaker than that of the molecular compound (80%). Secobarbital and the molecular compound slightly inhibited the neocortical augmenting and recruiting responses. Our findings suggest that although aminopyrine exerts a synergistic effect with secobarbital in inhibiting the EEG activation produced by MRF stimulation, in inhibiting the PHA-arousal response, there is no synergistic effect of the two drugs when they were given as the mixture. Moreover, the molecular compound rather than the mixture has a more potent inhibitory action on the EEG activation, particularly with PHA stimulation.

Inhibitory Action of the Combination of Aminopyrine and Secobarbital on EEG Activation, Neocortical Recruiting and Augmenting Responses in Rabbits

The effect of the combination of aminopyrine and secobarbital at a molar ratio of 2:1, the mixture and molecular compound, on rabbit EEG activation was examined. Secobarbital 40 mg/kg p.o. elevated threshold voltages in the neocortical and hippocampal EEG activation by high frequency electrical stimulation of the midbrain reticular formation (MRF), nucleous centralis medialis (CM) of the thalamus, and posterior hypothalamus (PHA) by 40, 40 and 80%, respectively. Aminopyrine 80 mg/kg p.o. alone did not affect the arousal responses. The molecular compound 120 mg/kg p.o. has more potent and long-lasting actions in inhibiting the arousal responses induced by the stimulation of MRF (80%) and CM (50%) than with secobarbital alone. The inhibitory action of the mixture 120 mg/kg p.o. on the PHA-arousal response (40 %) was significantly weaker than that of the molecular compound (80%). Secobarbital and the molecular compound slightly inhibited the neocortical augmenting and recruiting responses. Our findings suggest that although aminopyrine exerts a synergistic effect with secobarbital in inhibiting the EEG activation produced by MRF stimulation, in inhibiting the PHA-arousal response, there is no synergistic effect of the two drugs when they were given as the mixture. Moreover, the molecular compound rather than the mixture has a more potent inhibitory action on the EEG activation, particularly with PHA stimulation.

Conditioned modifications of arousal and unit activity in the rat hippocampus.

Two main types of neurons were recorded in the dorsal hippocampus of chronic rats. Type I neurons were characterized by a bursting mode of discharge. Their activity was higher during slow wave sleep (SWS) than during wakefulness (W) or paradoxical sleep (PS). They had an “inhibitory” response (decrease in spike frequency) to desynchronizing stimuli presented during a SWS episode. Type II neurons had a mean spike frequency greater than 10/s. Some of them, (group IIa), were more active during W and PS than during SWS and had an “excitatory” response (increase in spike frequency) to desynchronizing stimuli. Activity of other type II neurons, group IIb, had no relationship with the arousal level. An arousal response (neocortical EEG desynchrony) was classically conditioned to an acoustical CS. During that conditioning, most of the type I neurons rapidly displayed an inhibitory conditioned response (CR). This unit response was closely associated with the EEG CR. The majority of the type II neurons did not demonstrate signs of conditioning (group IIb). The others, group IIa, gradually developed an excitatory CR at moderate levels. This unit CR seemed to be independent of conditioned modifications of arousal.

Atropine stereotypy as a behavioral trap: a movement subsystem and electroencephalographic analysis.

An analysis was made of the movement subsystems involved in the stereotyped behaviors and electroencephalographic (EEG) activity that appear in rats given the anticholinergic drug atropine sulfate (50-75 mg/kg). One form of stereotypy occurred when the drugged faced the closed end of an alleyway. Instead of scanning briefly and then turning around to face the open end, as undrugged rats do, they typically "trapped", i.e., they continued to engage in rapid, repetitive scanning by the snout up and down or side to side along the surfaces of the closed end for long periods of time. Atropine appears to produce an exaggerated snout thigmotaxis. Accordingly, the behavioral pattern can be manipulated simply by changing the configuration of the environment, which alters sensory input to the snout. Therefore, such stereotyped behavior is not a motor automatism but rather a circular chain of reflexive reactions to surfaces which trap the animal. During rapid shifts in direction of movement in undrugged rats, there were often extremely brief periods of hippocampal theta that could be blocked by atropine. The presence of theta during such shifts might be important for normal behavioral sequencing. This could partially account for the fact that atropine-treated rats failed to change from their initial reactions in the alleyway to more adaptive behaviors. When a low roof was placed over the alleway, head scanning was greatly limited, and immobility in a lying posture rapidly became the more frequent behavior. This immobility was accompanied by a sleeplike (synchronized) neocortical EEG pattern rather than the activated (desynchronized) neocortical pattern that occurs during repetitive thigmotactic scanning. It is hypothesized that scanning stereotypy and activated EEG are maintained through movement-concurrent positive feedback.