Low Voltage Fast Activity Research Articles

Phasic relationship between the activity of basal forebrain neurons and cortical EEG in urethane-anesthetized rat

Previous studies have shown that a large number of neurons in the basal forebrain have higher firing rates when the cortical electroencephalogram (EEG) is characterized by low-voltage fast activity compared to states characterized by slow waves. A smaller number of cells with increased discharge rates during slow waves have also been observed. This putative ascending effect is thought to be tonic, but no attempt has been made to analyze a closer temporal correlation between the activity of basal forebrain neurons and the cortical EEG. Recordings were made from single units in the basal forebrain concurrently with the cortical EEG in urethane-anesthetized rats. A total of 52 neurons consistently showed higher firing during low-voltage fast activity (F-cells), whereas 14 neurons were consistently more active during cortical slow waves (S-cells). In most of the F- (90%) and S-cells (86%) the change in firing rate occurred prior to the change in the EEG. The average delay was 300–400 ms. At a deep level of anesthesia, the EEG was characterized by an alternation of flat periods and large waves. Most F-cells became active near the start of the first large wave, which is known to correspond to the onset of depolarization of cortical pyramidal neurons. In contrast, most S-cells were less active during the large waves. These data show that the activity of basal forebrain neurons is phasically correlated with the EEG in addition to the tonic correlation that has been demonstrated previously. Both types of basal forebrain neurons change their firing rate prior to the change in cortical EEG, suggesting that the basal forebrain neurons may have a regulatory influence on the EEG. © 1997 Elsevier Science B.V. All rights reserved.

Responses of cortical EEG-related basal forebrain neurons to brainstem and sensory stimulation in urethane-anaesthetized rats.

The basal forebrain can be considered to be a rostral extension of the ascending reticular activating system. A large number of neurons in the basal forebrain have been shown to display higher firing rates when low-voltage fast activity is present in the cortical EEG as opposed to states characterized by large slow waves in both unanaesthetized and anaesthetized animals. However, a smaller number of cells with increased discharge rate during slow waves was also observed in most of these studies. While it is likely that these two types of neurons have opposite roles in the regulation of cortical activation, it is not known how they respond to inputs from the brainstem or the periphery. In the present study, extracellular recordings were made in the basal forebrain of urethane-anaesthetized rats. A total of 52 neurons were studied in which the firing rate was significantly higher during fast cortical EEG waves (F-cells), and 14 neurons in which activity was significantly greater during slow waves (S-cells). The two cell types responded differently to stimulation of the pedunculopontine tegmental nucleus (PPT) and dorsal raphe nucleus (DRN) with short (0.5-1 s) trains of pulses and to noxious sensory stimuli (tail pinch). These stimulations excited most F-cells (80-96%) and inhibited the majority of S-cells (55-67%). In the few F-cells that were inhibited by stimulation, the response varied with the background firing rate of the cell: the higher the firing rate at the time of stimulation, the higher the probability of observing an inhibitory response. In contrast, single electrical pulses delivered to the PPT and DRN excited the majority (72%) of both F- and S-cells. Previous in vitro studies have shown that the application of acetylcholine or serotonin has predominantly inhibitory effects on basal forebrain cholinergic neurons. The predominantly excitatory effect of noxious, PPT and DRN stimulation on F-cells therefore suggests that glutamatergic or other excitatory afferents play a more dominant role in regulating basal forebrain neurons. We have previously shown that F-cells are more prevalent than S-cells. In combination, these findings suggest that basal forebrain neurons, and F-cells in particular, are important in mediating the ascending excitatory drive from the brainstem to the cerebral cortex.

Effect of arginine vasopressin on breathing movements of chronically instrumented fetal lambs.

In hypoxic conditions, fetal breathing movements (FBM) are reportedly inhibited with simultaneous elevation of the plasma level of catecholamines and arginine vasopressin (AVP). Although some kinds of catecholamines are reported to inhibit FBM, the effects of AVP on FBM are still unknown. The present study was undertaken to elucidate whether or not AVP has an inhibitory effect on FBM and electrocortical activities in chronically instrumented fetal lambs. Arginine vasopressin was injected slowly into the fetal external jugular vein via a catheter over a 30 minute period at an infusion rate of 4.9 approximately 10.0 mIU/minute/body. In 15 fetuses (36 estimations) the mean fetal age, mean estimated fetal body weight, and mean infusion dose were 132.4 +/- 4.5 days, 3.4 +/- 0.3 kg and 1.7 +/- 0.3 mIU/kg/min. The infusion caused a persistent decrease in the fetal heart rate and an increase in the fetal arterial pressure during the 30 minute period. The infusion of AVP resulted in a significant decrease in the incidence of FBM from 36.1 +/- 14.8% to 12.4 +/- 14.9% (p <0.01). However, there were no significant differences in the incidence of the low voltage fast (LVF) activity before and during infusion of AVP. AVP has an inhibitory effect on FBM. The mechanism of this inhibition was not a direct suppression of the CNS as there was a dissociation between FBM and the electrocortical activity during infusion of AVP.

Electroencephalographic findings of encephalitis in beagle dogs experimentally infected with canine distemper virus (CDV).

The present research study had two goals. Firstly, the effect of medetomidine/propofol on the electroencephalographic (EEG) recordings of nine SPF dogs was analysed. It was found that the basic pooled pattern of EEG recordings was characterized by a mean amplitude of 28 uV (range = 15-70 uV) and mean frequency of 1.8 Hz (range = 1-2.5 Hz), with superimposed low voltage (amplitude range = 4-20 uV; mean 14 uV) and fast activity (frequency range = 10-27 Hz; mean 18 Hz). All results were significantly constant (P < 0.05) and accurately reproducible (R = 0.70). The second goal was to investigate the value of EEG findings from dogs experimentally infected with canine distemper virus (CDV) under the same anaesthetic conditions, for the diagnosis of encephalitis. It was found that the EEG traces were characterized by high voltage, slow activity (HVSA) with superimposed low voltage, fast activity (LVFA). By comparing the mean values of amplitude and frequency for each single phase at different time intervals, it was found that only the mean value of the superimposed frequency was linearly distributed and changed significantly (P < 0.001). Thus, at least three readings should be taken from phase III of the EEG recording in order to obtain accurate values. The study has shown that electroencephalography can supply valuable information in cases of CDV encephalitis and can assist greatly in the differential diagnosis.

Clinical and electroencephalographic findings of inflammatory and infectious diseases of the central nervous system in dogs: a retrospective study.

In the present study medical records of 97 dogs with inflammatory/infectious diseases of the central nervous system (CNS), including 26 dogs with a history of seizures, were retrospectively examined. The aims of the study were to analyse the incidence rate of seizures, to search for criteria to recognize specific inflammatory diseases and to determine how far electroencephalography may be useful in the early confirmation of encephalitis and encephalitis-associated seizures. The incidence rate of seizures in this dog population was 26.8%, and dogs with protozoal encephalitis had the highest rate. Signalment, history, extraneural and neurological signs including localization contributed only a little to a specific diagnosis. Surprisingly focal clinical signs were observed in two-thirds of the dogs. Either focal or multifocal clinical signs were related mainly to the forebrain in dogs with a history of seizures and to the brainstem in dogs without seizures. Cerebrospinal fluid (CSF) analyses were useful to separate encephalitis from other CNS diseases and to distinguish certain conditions from others in approximately half the cases. Electroencephalography (EEG) revealed two distinct patterns in 25 examined dogs with histopathologically confirmed disease entities, which were characterized by high voltage, slow activity (HVSA) with superimposed low voltage, fast activity (LVFA). These changes were consistent and no significant differences (P > 0.05) between dogs with and without seizures, nor between different disease entities, were noted. However, all the dogs with seizures had in addition a uniform paroxysmal EEG activity with a high voltage (mean = 106.3 microV), fast activity (mean = 8.5 Hz) pattern. Moreover in several dogs from the present study this pattern had a focal distribution despite the fact that clinically seizures appear generalized. Therefore it was concluded that EEG may be a very helpful diagnostic tool to confirm an early diagnosis of encephalitis and to separate potential seizure cases from those without seizures.

The role of brain noradrenaline in cortical activation and behavior: A study of lesions of the locus coeruleus, medial thalamus and hippocampus-neocortex and of muscarinic blockade in the rat

Local injection of 6-hydroxydopamine in the locus coeruleus resulted in a 90% depletion of noradrenaline (NA) in the cerebral cortex as assessed by high-pressure liquid chromatography. This NA depletion had no effect on scopolamine-resistant hippocampal rhythmical slow activity and only an occasional effect on scopolamine-resistant neocortical low voltage fast activity. However, NE depletion resulted in a slight deficit in a behavioral swim-to-platform test and increased the deficit produced on the test by systemic treatment with scopolamine. Large surgical lesions of the medial thalamus or hippocampal formation plus posterior neocortex greatly increased the behavioral deficit produced by scopolamine. It is concluded that ascending noradrenergic projections play only a modest and possibly indirect role in the control of electrocortical activation and that a number of different brain lesions increase the behavioral impairment produced by central muscarinic blockade.

5-Hydroxytryptamine (5-HT) agonists: effects on neocortical slow wave activity after combined muscarinic and serotonergic blockade

In freely-moving rats treated with a combination of reserpine (10 mg/kg, i.p.) and scopolamine (5 mg/kg, i.p.), neocortical low voltage fast activity (LVFA) associated with continuous multiunit activity (MUA) was abolished and replaced by 2–6 Hz large irregular slow activity (LISA) above 1.5 mV associated with a burst-suppression pattern of MUA. Administration of the monoamine oxidase inhibitor pargyline (50–100 mg/kg, i.p.) completely suppressed 2–6 Hz LISA and restored normal-appearing LVFA and continuous MUA. The 5-hydroxytryptamine (5-HT) receptor agonists quipazine (0.5–20 mg/kg, i.p.), (±)-DOI (0.1–5 mg/kg, s.c.), and buspirone (0.1–10 mg/kg, i.p.), but not 8-hydroxy-2-(di- n-propylamine) tetraline (8-OH-DPAT, 0.05-0.8 mg/kg, s.c.) and RU 24969 (1–30 mg/kg, i.p.), produced a partial suppression of 2–6 Hz LISA and restored some lower voltage activity ( < 1 mV) above 6 Hz associated with continuous MUA. However, as opposed to pargyline, no receptor agonist tested restored continuous, normal-appearing LVFA. Even though agonists at 5-HT receptors can produce some activation of neocortical slow wave activity after combined cholinergic and serotonergic blockade, this effect is not equivalent to that observed after restoration of endogenous 5-HT transmission.

5-Hydroxytryptamine (5-HT) agonists: effects on neocortical slow wave activity after combined muscarinic and serotonergic blockade

In freely-moving rats treated with a combination of reserpine (10 mg/kg, i.p.) and scopolamine (5 mg/kg, i.p.), neocortical low voltage fast activity (LVFA) associated with continuous multiunit activity (MUA) was abolished and replaced by 2–6 Hz large irregular slow activity (LISA) above 1.5 mV associated with a burst-suppression pattern of MUA. Administration of the monoamine oxidase inhibitor pargyline (50–100 mg/kg, i.p.) completely suppressed 2–6 Hz LISA and restored normal-appearing LVFA and continuous MUA. The 5-hydroxytryptamine (5-HT) receptor agonists quipazine (0.5–20 mg/kg, i.p.), (±)-DOI (0.1–5 mg/kg, s.c.), and buspirone (0.1–10 mg/kg, i.p.), but not 8-hydroxy-2-(di- n -propylamine) tetraline (8-OH-DPAT, 0.05-0.8 mg/kg, s.c.) and RU 24969 (1–30 mg/kg, i.p.), produced a partial suppression of 2–6 Hz LISA and restored some lower voltage activity ( < 1 mV) above 6 Hz associated with continuous MUA. However, as opposed to pargyline, no receptor agonist tested restored continuous, normal-appearing LVFA. Even though agonists at 5-HT receptors can produce some activation of neocortical slow wave activity after combined cholinergic and serotonergic blockade, this effect is not equivalent to that observed after restoration of endogenous 5-HT transmission.

Cholinergic activation of the electrocorticogram: an amygdaloid activating system

In urethane-anesthetized rats, electrical 100-Hz stimulation of the basal amygdala changed neocortical electrical activity from 6-Hz or less large-amplitude, irregular slow activity to low-voltage fast activity (LVFA) including frequencies of above 10 Hz. A similar activating effect was seen in the hippocampus, where amygdala stimulation induced the appearance of rhythmical slow activity in the 2- to 6-Hz range. This activation of neocortical and hippocampal activity by amygdala stimulation was blocked by the cholinergic-muscarinic receptor antagonist scopolamine (0.5-5.0 mg/kg i.p.), but not by the peripheral antagonist methylscopolamine, in a concentration-dependent manner. In contrast, a blockade of ascending inputs from the midbrain to the neocortex by treatment with the serotonin-depletor p-chlorophenylalanine or cauterization of the rostral midbrain did not block neocortical LVFA to amygdala stimulation, even though the lesions abolished all LVFA to strong noxious stimuli such as tail pinches. Unilateral infusions of the local anesthetic lidocaine (1%) into the basal forebrain selectively blocked LVFA in the neocortex ipsilateral to the infusion. However, intracerebral or systemic administration of various excitatory amino acid antagonists (2-amino-5-phosphonovaleric acid, kynurenic acid, NPC 12626) was not effective in blocking LVFA to amygdala stimulation. An input from the amygdala to the basal forebrain cholinergic system appears to be one of multiple systems involved in the cholinergic activation of neocortical and hippocampal activity. Further, basal forebrain-cholinergic inputs to the cerebrum alone are sufficient to activate the electrocorticogram, as they sustain activation even in the absence of inputs from the mesencephalon.

Depth electrode studies and intracellular dentate granule cell recordings in temporal lobe epilepsy

Hippocampal depth electrodes are often used to localize seizure onset in patients who may have temporal lobe epilepsy (TLE). A number of features of the spontaneous seizures and of their ictal onset patterns can be analyzed from these recordings. We compared a number of the typical electroencephalographic (EEG) changes at seizure onset with several cellular parameters recorded in dentate granule cells from the same 14 patients diagnosed with medial temporal sclerosis (MTS) to examine the pathophysiological correlates of this spontaneous EEG activity in this form of TLE. The intracellularly recorded parameters include the propensity to fire evoked epileptiform bursts, the absence of evoked inhibitory potentials, the presence of polysynaptic excitatory postsynaptic potentials, and the presence of spontaneous excitatory activity. We noted several correlations between the EEG data and the intracellular recordings. The absence of synaptically evoked bursts was correlated with the presence of low-voltage fast activity at seizure onset. In addition, the loss of inhibitory postsynaptic potentials was correlated with the presence of periodic spiking pre-ictally. Several other correlations were also noted. These data indicate that EEG findings may be predictive of anatomical and cellular pathological changes and provide clues to the physiological mechanisms involved in this form of epilepsy.

Investigating the relationship between fetus EEG, respiratory, and blood pressure signals during maturation using wavelet transform.

In this study, we introduce the fast wavelet transform as a method for characterizing maturational changes in electrocortical activity, respiratory activity, and blood pressure in fetal lambs in early (110-122 days), mid (123-135 days), and late (136-144 days) third trimester (term 145 days). Each recording was 2 hr in duration. Wavelet decomposition was performed for six sets of parameters D2j where 1 < or = j < or = 6. The six series wavelet transforms represent the following signal frequency bands: 1. 16-32 Hz; 2. 8-16 Hz; 3. 4-8 Hz; 4. 2-4 Hz; 5. 1-2 Hz; 6. 0.5-1 Hz. In the early group, power in the electrocephalogram (EEG) was highest in the fourth wavelet band, with relatively low power in the other bands. Increase in gestational age was characterized by increased power in all four wavelet bands. Power in the first wavelet band was significantly increased during low-voltage fast activity (LVFA) in the late group. The respiratory and blood pressure signals showed common frequency components with respect to time and were coincident with the LVFA EEG signal. Respiratory activity was only observed during some of the LVFA periods and was completely absent during high-voltage slow activity (HVSA) EEG. The respiratory signal showed dominant power in the fourth wavelet band, and less power in the third and fifth band. The blood pressure signal was also characterized by dominant power in the fourth wavelet band. This power was significantly increased during periods of respiratory activity. These results suggest a strong relationship between fetal EEG, blood pressure, and breathing movements.

Investigating the effects of opioid drugs on electrocortical activity using wavelet transform.

Fetal electrocortical activity (ECoG) is characterized by two distinct patterns: HVSA (high voltage, slow activity) and LVFA (low voltage, fast activity). Using the wavelet transform (WT), we recently reported that the frequency characteristics of these two ECoG patterns undergo significant maturational changes prior to birth (Akay et al. 1994a). We now report that fetal ECoG can also be significantly affected by pharmacological agents. In this paper, we compared the effects of two opioid drugs (morphine and [D-Pen2, D-Pen5]-enkephalin, DPDPE) on fetal ECoG, using the chronically instrumented fetal lamb model. Morphine was infused intravenously (i.v.) at 2.5 mg/h, while DPDPE was infused into the lateral cerebroventricle (i.c.v.) at 30 micrograms/h. The ECoG was analyzed using WT. We performed multi-resolution decomposition for four sets of parameters D2j where -1 < j < -4. The four series WTs represent the detail signal bandwidths: (1) 16-32 Hz, (2) 8-16 Hz, (3) 4-8 Hz, (4) 2-4 Hz. The data were subjected to statistical analysis using the Kolmogorov-Smirnov (KS) test. Both morphine and DPDPE resulted in a significant increase in power in the first wavelet band, while power was reduced in the second, third and fourth wavelet bands. In addition, both drugs resulted in a disruption of the normal cyclic pattern between the two ECoG patterns. There was a difference in the time course of action between morphine and DPDPE. This is the first occasion in which continuous ECoG has been subjected to rigorous statistical analysis. The results suggest that the WT-KS method is most suitable for quantitating changes in the ECoG induced by pharmacological agents.

Do cortical and thalamic bioelectric oscillations have a functional role? A brief survey and discussion

This paper first briefly describes rhythmic bioelectric oscillations that can be recorded from the neocortex (particularly in cats). This descriptive section is followed by a review of the mechanisms whereby these rhythms are generated, and a section in which we try to go beyond the purely correlative aspect and discuss the possible functional role of synchronized oscillations in thalamo-neocortical channels. Based on the literature data, it seems that two distinct and opposite roles can be attributed to these oscillations: either to lower the level of awareness, such as in slow wave sleep, when these oscillations are widespread on the neocortex; or to contribute to perceptual processing, when these rhythms are more localized and possibly of a higher frequency. Electrocortical (ECoG) rhythmical activities have been known and described since the early days of electrophysiological explorations of the human and animal brain. Surprisingly though, little importance has generally been attached to these oscillatory activities, except as indicators of sleep stages in animals and humans and, in the case of the alpha rhythms (the first rhythm to be discovered in the thirties by Hans Berger), of a certain state of ‘relaxation’ in humans. Despite the well-accepted fact that the human alpha rhythm evidently occurs during waking (even if it is in a ‘relaxed’ state), the idea has curiously prevailed that the waking (‘aroused’) state in general is mostly characterized by low voltage fast (‘desynchronized’) activity. It is only more recently that some studies have suggested a functional importance of a variety of regular oscillatory activities that can be recorded from the neocortex and/or from a variety of thalamic nuclei not only in the sleeping but also on the waking, behaving animal. This review considers possible reasons indicating that these rhythmical activities are more than just epiphenomena. Our analysis is essentially restricted to the cat, with only a very quick glance at other species.

Entorhinal-hippocampal interactions in medial temporal lobe epilepsy.

Experimental studies suggest important interactions between hippocampus and entorhinal cerebral cortex in generation of temporal lobe seizure activity. We studied electrical expression of spontaneous temporal lobe ictal activity in hippocampus and entorhinal cortex in 9 medically refractory epileptic patients who had intracranial depth and subdural electrodes implanted during surgical evaluation. All 9 patients subsequently underwent anteromedial temporal lobectomy with hippocampectomy, all had > 50% decrease in neuronal cell density in hippocampal CA1 and CA3, and all had good to excellent seizure outcome after operation. Two to 10 spontaneous seizures were analyzed per patient (total 41 seizures). Nine patients had variable onset of seizure activity recorded in hippocampus, entorhinal cortex, or both simultaneously. Low-voltage fast activity was observed in either location and varied among seizures in an individual patient. Periodic preictal spikes, when present, were often synchronous in both locations, but were noted independently only in hippocampus. Our data suggest that preictal spikes and low-voltage fast seizure discharges have anatomically distinct origins, and that some syndromes of medial temporal lobe epilepsy involve interactions between entorhinal and hippocampal regions that act together to produce and propagate the seizures in such patients.

Time-frequency analysis of the electrocortical activity during maturation using wavelet transform.

In this study, we introduce the wavelet transform (WT) as a method for characterizing the maturational changes in electrocortical activity in 24 fetal lambs ranging from 110-144 days gestation (term 145 days). The WT, based on multiresolution signal decomposition, is free of assumptions regarding the characteristics of the signal. The approximation of the electrocortical activity at resolutions varying from 2j+1 to 2j can be extracted by decomposing the signal on a wavelet orthonormal basis of L2(R). We performed multiresolution decomposition for four sets of parameters D2j, where -1 < j < -4. The four series WT represent the detail signal band-widths: (1) 16-32 Hz, (2) 8-16 Hz, (3) 4-8 Hz, (4) 2-4 Hz. The data were divided into three groups according to gestational age: 110-122 days (early), 123-135 days (middle), and 136-144 days (late). In the early group, the power was highest in the fourth signal bandwidth, with relatively low power in the other bands. Increase in gestational age was characterized by increased power in all four bandwidths. Comparison of the cumulative distribution function of the power in the four wavelet bands confirmed the presence of two statistically different patterns in all three age groups. These two patterns correspond to the visually identified patterns of HVSA (high-voltage slow activity) and LVFA (low-voltage fast activity). The earliest development change occurred in HVSA, with progressive increase in power in the 2-8 Hz band. Later changes occurred in LVFA, with a significant increase in power in the 16-32 Hz band.(ABSTRACT TRUNCATED AT 250 WORDS)

Modification of neocortical acetylcholine release and electroencephalogram desynchronization due to brainstem stimulation by drugs applied to the basal forebrain

Acetylcholine released from the cerebral cortex was collected using microdialysis while stimulating the region of the pedunculopontine tegmentum in urethane-anesthetized rats. Electrical stimulation in the form of short trains of pulses delivered once per minute produced a 350% increase in acetylcholine release and a desynchronization of the electroencephalogram, as measured by relative power in the 20–45 Hz range (low-voltage fast activity). Perfusion of the region of cholinergic neurons believed to be responsible for the cortical release of acetylcholine, the nucleus basalis magnocellularis, was carried out using a second microdialysis probe. Exposure of the nucleus basalis magnocellularis to blockers of neural activity (tetrodotoxin or procaine) or to blockers of synaptic transmission (calcium-free solution plus magnesium or cobalt) produced a substantial decrease in the release of acetylcholine and desynchronization evoked by brainstem stimulation. Exposure of the nucleus basalis magnocellularis to the glutamate antagonist, kynurenate, resulted in a decrease in evoked acetylcholine release and electroencephalogram desynchronization similar in magnitude to that produced by nonspecific blockers, whereas application of muscarinic or nicotinic cholinergic blockers to the nucleus basalis magnocellularis did not reduce acetylcholine release or electroencephalogram desynchronization. Application of tetrodotoxin to the collection site in the cortex abolished the stimulation-evoked acetylcholine release, but not the low baseline release indicating that cholinergic nucleus basalis magnocellularis neurons have a low spontaneous firing rate in urethane-anesthetized animals. The results of this study suggest that the major excitatory input to the cholinergic neurons of the nucleus basalis magnocellularis from the pedunculopontine tegmentum is via glutamatergic and not cholinergic synapses.

Histamine does not play an essential role in electrocortical activation during waking behavior

Intraperitoneal injection of α-fluoromethylhistidine (α-FMH; 200 mg/kg), a specific inhibitor of histidine decar☐ylase produced a severe depletion of neorcortical and hippocampal histamine 3 h later as determined by a radioenzymatic assay. This treatment had no obvious effect on either low voltage fast activity (LVFA) in the neocortex or on rhythmical slow activity (RSA) in the hippocampus during an 8 h recording period during the rats' light cycle. Scopolamine-sensitive LVFA, scopolamine-resistant LVFA and scopolamine-resistant hippocampal RSA all appeared unaffected. This suggests that any contribution histamine makes to electrocortical activation is probably indirect, acting via other transmitter systems.

Effects of some cholinergic agonists on neocortical slow wave activity in rats with basal forebrain lesions

Chronic rats, prepared with unilateral injections of kainic acid in the left basal forebrain, displayed prominent large amplitude slow wave activity in the neocortex ipsilateral to the injection. Oxotremorine and pilocarpine, given systemically following pretreatment with methyl scopolamine to block peripheral muscarinic effects, restored low voltage fast activity (LVFA) in a dose-related manner. Oxotremorine was more potent than pilocarpine. Arecoline was not consistently effective. Tetrahydroaminoacridine abolished abnormal 4–6 Hz rhythmical slow waves in the left neocortex but had little effect on large amplitude irregular slow waves. Direct-acting cholinergic agonists can restore near-normal neocortical activity after extensive cholinergic deafferentation of the neocortex.

Intracerebral low frequency electrical stimulation: a new tool for the definition of the "epileptogenic area"?

Low Frequency (1 Hz) Electrical Stimulation (LFES) has been systematically utilized, during stereo-EEG investigations, in 24 consecutive young adult patients considered for surgical treatment of severe drug-resistant partial epilepsy. Ninety seizures (1-14/patient) identical to the spontaneous ones previously recorded were thus obtained in 19 patients (79%). LFES is less effective for induction of seizures than high frequency (50 Hz) stimulation (5.9% vs 22.9%), and it also provokes less "false positive" responses (1% vs 17%). The main "sensitive" structures to LFES are the hippocampus, the amygdala, and the hippocampal gyrus. However, seizures were also induced by stimulating the temporal lobe white matter, the temporal pole, and the temporal neocortex, as well as the orbito-frontal cortex (in the only patient with fronto-temporal epilepsy). The more frequently observed electrical pattern is a gradual increase of spikes and spikes and waves frequency, with or without occurrence of low voltage fast activity. The high percentage of early "subjective" manifestations similar to the spontaneous ones, the lack of major electrical artifact, and the good visualization of the spatial evolution of the induced-discharge, strongly suggest that LFES is of great help for defining the "epileptogenic area".

Behavior-related cortical activity and swim-to-platform performance in the aged rat

Aged rats (26 months) usually retained normal acetylcholine-dependent and serotonin-dependent forms of neocortical low-voltage fast activity and serotonin-dependent hippocampal rhythmical slow-wave activity. In a simple swim-to-platform test, aged rats (23 and 26 months) performed normally in acquisition and in retention over a 7-day period. The results are discussed in relation to the common assumption that aged rats provide a valid model of human senile dementia.