Biomedical subjects

A M Coenen

Publications and source records attributed to A M Coenen.

At least 19 recordsLinked to original sources

PubMed2001

Electrophysiological and pharmacological characteristics of two types of spike-wave discharges in WAG/Rij rats.

Rats of the WAG/Rij strain are commonly seen as a genetic model for generalised absence epilepsy in man. Interestingly, generalised absence epilepsy shows, in addition to the fully generalised spike-wave discharges, a second type of spike-wave discharge, which lasts for a shorter time, has a lower frequency, and a lower incidence. The originally described distinction between the two types of spike-wave discharges was mainly based on the shape, polarity and duration of the discharges. In the present study other characteristics such as the spatial and temporal distribution of the spike and wave components of the two discharges and frequency spectra were found to differ between the two types. In addition, a reciprocal regulation of the two types of spike-wave discharges by drugs affecting the dopaminergic system (haloperidol and apomorphine) was observed. The results convincingly demonstrate the difference between the two phenomena and warrant the search for neurobiological mechanisms underlying both types of spike-wave discharges.

Action Potentials↗

PubMed2001

Auditory evoked potentials from auditory cortex, medial geniculate nucleus, and inferior colliculus during sleep-wake states and spike-wave discharges in the WAG/Rij rat.

OBJECTIVE: Click auditory evoked potentials (AEP) were simultaneously recorded from the auditory cortex (ACx), the medial geniculate nucleus (MGN), and the inferior colliculus (IC) in the freely moving WAG/Rij rat, to investigate state-dependent changes of the AEP in different anatomical locations along the auditory pathway. METHODS: AEPs obtained during active (AW) and passive wakefulness (PW), slow wave sleep (SWS), rapid-eye-movement sleep (REM) and generalized spike-wave discharges (SWD; a specific trait of the WAG/Rij rat, a genetic model for absence epilepsy), were compared. RESULTS: The early components in ACx, MGN and IC were stable throughout the sleep-wake cycle and SWD, apart from a slight increase in the IC during SWD. At all three locations a prominent enlargement of a later component (i.e., N32 in IC, N33 in MGN, and N44 in ACx) was found during SWS and SWD. CONCLUSIONS: The early AEP components are not modulated by the normal sleep-wake states, and are not impaired during SWD. A strong state-dependent modulation of a later AEP component occurs at all three anatomical locations investigated. This suggests that apart from the thalamic burst firing mode, additional mechanisms must exist for the enlargement of the AEP during EEG-synchronized states at the prethalamic and cortical level.

Action Potentials↗

PubMed2001

Sensory gating of auditory evoked potentials in rats: effects of repetitive stimulation and the interstimulus interval.

In the P50 gating or conditioning-testing (C-T) paradigm, the P50 response, a small positive midlatency ( approximately 50 ms after stimulus onset) component of the human auditory evoked potential (AEP), is reduced towards the second click (S2) as compared to the response to the first click (S1). This phenomenon is called sensory gating. The putative function of sensory gating is thought to protect subjects from being flooded by irrelevant stimuli. Comparative studies have been done in rats in order to elucidate the underlying neural substrate of sensory gating. However, for a direct comparison of rat and human AEP components, it is imperative for both components to show similar characteristics. The amount of sensory gating in humans is dependent on repetitive stimulation and the interstimulus interval (ISI). In the present study effects of repetitive stimulation (Experiment 1) and various ISIs (Experiment 2) were determined on rat AEP components. The results demonstrate that gating is not limited to a restricted cortical area or a single midlatency component and that repetitive stimulation and ISI affect gating of several rat AEP components. Components such as the vertex P17 and N22 show a decrease in gating within several S1-S2 presentations, mainly due to a decrease in amplitude to S1 (Experiment 1). Gating for vertex components (such as the P17, N22 and N50) is ISI dependent (Experiment 2), but there is no interval in the 200-600 ms range at which optimal gating occurs. The ISI effects on gating are due to an increase of the amplitude to S2. The results have implications for the discussion about the rat homologue of the human P50.

Animals↗

PubMed2001

Melatonin for chronic sleep onset insomnia in children: a randomized placebo-controlled trial.

To establish the efficacy of melatonin treatment in childhood sleep onset insomnia, 40 elementary school children, 6 to 12 years of age, who suffered more than 1 year from chronic sleep onset insomnia, were studied in a double-blind, placebo-controlled study. The children were randomly assigned to receive either 5-mg melatonin or placebo. The study consisted of a 1-week baseline, consecutively followed by a 4-week treatment period. After that period, treatment was continued if the parents wished so. The study's impact was assessed by measurements of lights-off time, sleep onset, and wake-up time, recorded in a diary (n = 33). Sleep onset was also recorded with an actigraph (n = 25). Endogenous dim light melatonin onset was measured in saliva (n = 27). Sustained attention was evaluated with the Bourdon-Vos reaction time test (n = 36). In the melatonin group, mean (95% CI) lights-off time advanced 34 (6-63) minutes, diary sleep onset 63 (32-94) minutes, actigraphic sleep onset 75 (36-114) minutes, and melatonin onset 57 (24 to 89) minutes; total sleep time increased 41 (19-62) minutes. In the placebo group, these parameters did not shift significantly. The change during the 4-week treatment period differed between the treatment groups significantly as to lights-off time, diary and actigraphic sleep onset, sleep duration, and melatonin onset. There were no significant differences between the treatment groups in the change of sleep latency, wake-up time, and sustained attention reaction times. Mild headache occurred in 2 children during the first 2 days of the melatonin treatment. Eighteen months after the start of the trial, in 13 of the 38 children who could be followed up, melatonin treatment was stopped because their sleep problem was solved and in 1 child because sleep was not improved. Twelve children used melatonin 5 mg, the other 1.0 to 2.5 mg. One child developed mild generalized epilepsy 4 months after the start of the trial. The results show that melatonin, 5 mg at 6 PM, was relatively safe to take in the short term and significantly more effective than placebo in advancing sleep onset and dim light melatonin onset and increasing sleep duration in elementary school children with chronic sleep onset insomnia. Sustained attention was not affected.

Child↗

PubMed2000

The influence of diazepam on the electroencephalogram-evoked potential interrelation in rats.

Though being a sedative, diazepam increases beta-activity in the electroencephalogram (EEG). Diazepam also affects auditory evoked potentials (AEPs). We investigated if the effect of diazepam on AEPs could be ascribed to its beta-increasing effect. Eight rats received vehicle and diazepam counterbalanced. AEPs were ranked in ten categories according to the percentages of beta-activity in the pre-stimulus electroencephalogram (EEG). With vehicle, the P(29), N(51) and P(67) AEP components increased and cross-correlation coefficients (CCCs) declined with increasing beta-activity. With diazepam AEP components and CCCs remained unchanged. All AEPs with diazepam closely resembled the AEP of the lowest beta-category obtained with vehicle. We conclude that the effect of diazepam on AEPs can not be ascribed to its beta-enhancing effect. Diazepam disrupts the normal AEP-EEG relation such that diazepam-effects on AEPs seem to reflect the sedative effects of diazepam and not its beta-increasing effects.

Animals↗

PubMed2000

Effects of melatonin on the quality of life in patients with delayed sleep phase syndrome.

OBJECTIVE: The purpose of this study was to compare health-related quality of life of delayed sleep phase syndrome (DSPS) patients with a random Dutch sample and four samples of patients with other chronic conditions. We also investigated the effectiveness of treatment with 5 mg of melatonin on the quality of life of DSPS patients. METHODS: Forty-three DSPS patients completed a quality-of-life questionnaire (Medical Outcome Study Short Form-36 [MOS SF-36] health survey) just before and 2-9 months after participation in a clinical trial involving the administration of melatonin. Scores were compared with responses to the same survey by a random Dutch sample and by patients with sleep apnea, clinical depression, migraine, and osteoarthritis. RESULTS: MOS SF-36 scales scores were significantly lower in DSPS patients relative to age- and gender-adjusted norms for the Dutch sample. Some health dimensions were more affected, and others less affected, by DSPS compared with the other chronic conditions. Melatonin treatment improved all scales except the scale "role due to emotional problems." CONCLUSION: DSPS has a unique significant quality-of-life burden that seems to be improved by treatment with melatonin.

Adult↗

PubMed2000

Correlation dimension of the human electroencephalogram corresponds with cognitive load.

This study aimed at assessing the effects of cognitive activity and mental task load on the correlation dimension of the human electroencephalogram (EEG). Three experimental conditions were created: a baseline condition and two cognitive task conditions, a calculation task and a time estimation task. The calculation task was supposed to induce a higher mental load than the time estimation task, which is regarded as a less complex one. This was verified by a subjective rating scale. All conditions differed significantly in subjective estimated task load. The correlation dimension appeared to be higher in both task conditions compared to the baseline condition. A comparison of the two tasks indicated that the difference in correlation dimension between calculation and time estimation was also significant, with the highest value for calculation. It is concluded that cognitive and mental activity is associated with a higher correlation dimension in the EEG. This implies that the correlation dimension is a sensitive parameter in the analysis of electrical brain activity.

Adult↗

PubMed2000

Effects of diazepam on auditory evoked potentials of rats elicited in a ten-tone paradigm.

The effect of diazepam on sensory gating was studied in rats by measuring diazepam effects on auditory evoked potentials (AEPs) elicited in a ten-tone paradigm. Trains of 10 repetitive tone-pip stimuli were presented. Rats (n = 8) received 4 mg x kg(-1) diazepam subcutaneously or vehicle, counterbalanced over two sessions. Diazepam decreased the amplitude of the middle-latency P30 component and increased the amplitudes of the late-latency N60 and P67 components. The increase in the late-latency components might be due to a diazepam-induced decrease in arousal. Stimulus repetition decreased the amplitudes of the middle-latency N18 and P30 components in both conditions. This suggests that automated neuronal recovery functions underlying sensory gating remain intact with diazepam. In the vehicle condition, the amplitude of the late-latency P67 decreased with stimulus repetition, but not in the diazepam condition. This suggests a diazepam-induced decrease of behaviourally mediated habituation.

Acoustic Stimulation↗

PubMed1999

Differential effects of ketamine on gating of auditory evoked potentials and prepulse inhibition in rats.

Schizophrenic patients suffer from deficits in information processing. Patients show both a decrease in P50 gating [assessed in the conditioning-testing (C-T) paradigm] and prepulse inhibition (PPI), two paradigms that assess gating. These two paradigms might have a related underlying neural substrate. Gating, as measured in both the C-T paradigm (the gating of a component of the auditory evoked potential (AEP)], and PPI can easily be measured in animals as well as in humans. This offers the opportunity to model these information processing paradigms in animals in order to investigate the effects of neurotransmitter manipulations in the brain. In order to validate the animal model for disturbances in AEP gating, d-amphetamine (0.5 and 1 mg/kg, i.p.) was administered. Gating of an AEP component was changed due to injection of d-amphetamine (1 mg/kg) in the same way as seen in schizophrenic patients: both the amplitude to the conditioning click and the gating were significantly reduced. Next, the effect of the N-methyl-D-aspartate (NMDA) antagonist ketamine (2.5 and 10 mg/kg, i.p.) was investigated to assess its effects in the two gating paradigms. It was found that ketamine (10 mg/kg) did not affect gating as measured with components of the AEP. However, ketamine (10 mg/kg) disrupted PPI of the startle response to the extent that prepulse facilitation occurred. Firstly, it is concluded that AEP gating was disrupted by d-amphetamine and not by ketamine. Secondly, PPI and the C-T paradigm reflect distinct inhibitory sensory processes, since both paradigms are differentially influenced by ketamine.

Animals↗

PubMed1999

Effects of neurosteroids on spike-wave discharges in the genetic epileptic WAG/Rij rat.

Effects of i.p. administration of the neurosteroids, allopregnanolone and pregnenolone sulfate, were studied in WAG/Rij rats, a genetic model for generalized absence epilepsy. EEG recordings showed that allopregnanolone, a positive modulator of the GABA(A) receptor, in doses ranging from 5 to 20 mg/kg, increased dose-dependently the number- and total duration of spike-wave discharges. Pregnenolone sulfate, a positive modulator of NMDA receptors, also increased those parameters, though only at the highest dose used (100 mg/kg). Significant changes in spike-wave discharges occurred during the first hour post-injection and were not accompanied with behavioral alterations. The obtained data indicate that both these neurosteroids aggravate the spike-wave activity. This finding contrasts with the anti-convulsant effects of some neurosteroids and they point to a different pharmacological profile of epilepsy with convulsive or non-convulsive seizures.

Animals↗

PubMed1998

Time course of chronic diazepam effects on the auditory evoked potential of the rat.

The time course of chronic diazepam effects on auditory evoked potentials was studied in rats. Auditory evoked potentials were elicited by background and target tones in a passive oddball paradigm. Diazepam was administered by slow release implants to establish constant blood concentrations. Recordings were made during 21 days of treatment and 9 days after treatment ceased. Diazepam increased the amplitude of the P40 component and decreased the amplitude of the P72-P102 components elicited by background tones. Diazepam increased the amplitude of the P40-P48 component and decreased that of the N58 component elicited by target tones. These effects remained constant during treatment. Diazepam further decreased the amplitude of the P102 component elicited by target tones. This effect became more distinct over time. No group differences were found 9 days after treatment. The constant drug effects on middle-latency components (P40-P48) might reflect diazepam-induced changes in sensory information processing. The decreased long-latency component (P102) might reflect a diminished attention to, or discrimination of, target tones. The time course of this effect might reflect diazepam-enhanced habituation.

Animals↗

PubMed1998

Neuronal phenomena associated with vigilance and consciousness: from cellular mechanisms to electroencephalographic patterns.

The neuroanatomical substrates controlling and regulating sleeping and waking, and thus consciousness, are located in the brain stem. Most crucial for bringing the brain into a state conducive for consciousness and information processing is the mesencephalic part of the brain stem. This part controls the state of waking, which is generally associated with a high degree of consciousness. Wakefulness is accompanied by a low-amplitude, high-frequency electroencephalogram, due to the fact that thalamocortical neurons fire in a state of tonic depolarization. Information can easily pass the low-level threshold of these neurons, leading to a high transfer ratio. The complexity of the electroencephalogram during conscious waking is high, as expressed in a high correlation dimension. Accordingly, the level of information processing is high. Spindles, and alpha waves in humans, mark the transition from wakefulness to sleep. These phenomena are related to drowsiness, associated with a reduction in consciousness. Drowsiness occurs when cells undergo moderate hyperpolarizations. Increased inhibitions result in a reduction of afferent information, with a lowered transfer ratio. Information processing subsides, which is also expressed in a diminished correlation dimension. Consciousness is further decreased at the onset of slow wave sleep. This sleep is controlled by the medullar reticular formation and is characterized by a high-voltage, low-frequency electroencephalogram. Slow wave sleep becomes manifest when neurons undergo a further hyperpolarization. Inhibitory activities are so strong that the transfer ratio further drops, as does the correlation dimension. Thus, sensory information is largely blocked and information processing is on a low level. Finally, rapid eye movement sleep is regulated by the pontine reticular formation and is associated with a "wake-like" electroencephalographic pattern. Just as during wakefulness, this is the expression of a depolarization of thalamocortical neurons. The transfer ratio of rapid eye movement sleep has not yet been determined, but seems to vary. Evidence exists that this type of sleep, associated with dreaming, with some kind of perception and consciousness, is involved in processing of "internal" information. In line with this, rapid eye movement sleep has higher correlation dimensions than slow-wave sleep and sometimes even higher than wakefulness. It is assumed that the "near-the-threshold" depolarized state of neurons in the thalamus and cerebral cortex is a necessary condition for perceptual processes and consciousness, such as occurs during waking and in an altered form during rapid eye movement sleep.

Consciousness↗

PubMed1998

Cortical and thalamic visual evoked potentials during sleep-wake states and spike-wave discharges in the rat.

Flash visual evoked potentials (VEP) were simultaneously recorded from the primary visual cortex and the dorsal lateral geniculate nucleus in freely-moving WAG/Rij rats, to investigate whether the thalamic VEP shows the same state-dependent alterations as the cortical VEP. VEPs obtained during active and passive wakefulness (AW and PW), slow-wave sleep (SWS), REM sleep and during the occurrence of spike-wave discharges (SWD), a specific trait of the genetically epileptic WAG/Rij rat, were compared. The general architecture of the thalamic VEP resembles the cortical VEP, although its polarity is reversed. This facilitated the interpretation of components in terms of underlying neuronal events. The primary excitation peak is differently modulated in cortex and thalamus. Whereas the thalamic component (P30) is not affected by brain-state, the cortical component (N1) shows a strong increase in latency during SWS and SWD. In contrast, the modulation of later components is highly similar for cortex and thalamus. VEPs obtained during AW and REM resemble each other. During SWS and SWD there is a considerable, and during PW a moderate, enlargement of primarily inhibitory components. After-discharges are enhanced during SWS, SWD and REM. No evidence is found for a major impairment of sensory transmission during SWD.

Action Potentials↗

PubMed1998

Neurotrophic ACTH4-9 analogue therapy normalizes electroencephalographic alterations in chronic experimental allergic encephalomyelitis.

Chronic experimental allergic encephalomyelitis (CEAE) is an established experimental model for multiple sclerosis (MS). The demyelinating lesions in the white matter of the central nervous system observed in CEAE and in MS are accompanied by various neurophysiological alterations. Among the best defined electrophysiological abnormalities are the changes in event-related potentials, in particular evoked potentials involving the spinal cord, i.e. motor and sensory evoked potentials. Less familiar are the changes observed in the electroencephalogram of CEAE-affected animals, which are also encountered in the human equivalent, MS. In the present experiment we evaluated the therapeutic value of a neurotrophic peptide treatment [H-Met(O2)-Glu-His-Phe-D-Lys-Phe-OH, an ACTH4-9 analogue] and its effect on the delayed flash visual evoked potentials (VEP) and power spectra of the electroencephalogram, during a 17-week follow-up of CEAE. CEAE animals treated with the neurotrophic peptide were protected against the development of neurological symptoms during the course of the demyelinating syndrome. VEPs of animals suffering from CEAE showed a delay of the latencies of the late components which was significantly counteracted by peptide treatment. The peak-to-peak amplitude of the VEP afterdischarge recorded from CEAE animals was significantly increased during the course of CEAE and correlated closely with the progression of the myelinopathy. Furthermore, CEAE animals showed an increase of electroencephalogram (EEG) beta activity of up to 500% as compared with the age-matched control group. This increase in beta power mainly consisted of a prevailing 20-21 Hz peak, a frequency that normally is not dominant in control EEG recordings of the rat during passive wakefulness. All these electrophysiological phenomena were absent in ACTH4-9 analogue-treated animals. The present findings underscore the potential importance of a neurotrophic peptide treatment in the pharmacotherapy of central demyelinating syndromes, and possibly of MS.

Adrenocorticotropic Hormone↗

PubMed1998

Differential effects of non-REM and REM sleep on sensory gating in rats.

Sensory gating in rats can be measured with a double click paradigm. The diminished response towards the second click is a physiological manifestation of reduced sensory input. This physiological process seems to be disturbed in human psychoses. It is thought that gating, as measured with this paradigm, is a preattentive, involuntary phenomenon which is not modulated by attention. If this is indeed the case, than it is hypothesized that gating should not be modulated by non-REM sleep. In the present experiment pairs of clicks (500 ms interval) were presented during wakefulness, non-REM as well as REM sleep and cortical auditory evoked potentials (AEP's) were recorded in chronically implanted rats. Rather similar AEP's were found after the first and second stimulus. However, the amplitudes of the various components of the second AEP were smaller than those of the first AEP, suggesting a gated response. This was the case during all three levels of vigilance. The amplitudes of both AEP's showed the more often reported changes in amplitude during sleep and REM sleep. Clear differences were seen in gating: compared to wakefulness a decrease in gating was found during REM sleep while gating was unchanged during non-REM sleep. The latter outcome seems to confirm that gating in rats is indeed a preattentive process. Finally, results were discussed in terms of neuronal properties of thalamic relay cells and it is suggested that firing properties of thalamic relay cells are not involved in this type of sensory gating.

Acoustic Stimulation↗

PubMed1997

Event-related potentials in a passive and active auditory condition: effects of diazepam and buspirone on slow wave positivity.

The effects of single, oral doses of diazepam (10 mg), buspirone (10 mg) and placebo on auditory event-related potentials were assessed in healthy volunteers. Subjects received two series of auditory stimuli: a series of identical stimuli presented in a neutral, passive condition and a series of identical standard tones (P = 0.8), but now intermixed with target tones (P = 0.2), in an active, oddball condition. The analysis focused on the average value of the potential in two different phases, from 250 till 574 ms post-stimulus (including P300) and from 576 till 900 ms post-stimulus (including late slow wave positivity). Event-related potentials for the standards of the oddball task were compared with the potentials of the same stimuli presented in the neutral condition. In addition, the classical comparison between the target and the standard in the oddball task was made. The first comparison was designed to isolate any effect of a change in the level of vigilance and attention due to involvement in the oddball task. This effect was evident as an increase in positivity that was smaller in the diazepam condition. The second comparison was designed to isolate the distinctive processing associated with task-relevant stimuli. This revealed that the P300 was reduced in the 250-574 ms window in the diazepam group. Both results suggest that cognitive processing of relevant stimuli is reduced by diazepam. Presumably, this is associated with the sedative effects of this drug. Consistent with this interpretation, subjects under the influence of diazepam made more omissions in the detection of targets in the oddball condition and had longer reaction times. In contrast to diazepam, the anxiolytic buspirone did not appear to have measurable effects on cognition.

Adult↗

PubMed1997

Influence of diazepam and buspirone on human heart rate and the evoked cardiac response under varying cognitive load.

The influence of two anxiolytics on basal heart rate and on the evoked cardiac response elicited by auditory stimuli, was studied in humans. Diazepam (Valium) (7.5 mg) and buspirone (Buspar) (7.5 mg), which differ in their psycho-pharmacological profiles, were used. Prestimulus vigilance and cognitive load were manipulated by instructions allowing the subjects to ignore the stimuli, or requiring them to count the tones. Drug effects were obtained in subjective alertness, basal heart rate level, and the evoked cardiac response. Diazepam reduced subjective alertness, while buspirone did not. Diazepam apparently increased heart rate levels relative to placebo, in contrast to buspirone, which produced an apparent decrease in heart rate. These drug-induced prestimulus heart rate level effects were associated with differential decelerations immediately following stimulus onset and appear to reflect differences in prestimulus vigilance. Opposite effects of the drugs were also observed in the second, acceleratory, component of the of the evoked cardiac response, and these were found to be independent of the prestimulus drug effects. Compared with placebo, buspirone appeared to enhance the acceleratory component in the count condition, while diazepam led to an apparent reduction of this component. Enhancement of this acceleration after buspirone may reflect an increase in cognitive effort directed to the performance of task-relevant behaviour, while the reduction of this component after diazepam can be regarded as a cognitive-motivational neutralisation of signal value. The differential effects of the two anxiolytics support the separation of the evoked cardiac response into different components and may also have implications for the clinical use of the drugs.

Acoustic Stimulation↗

PubMed1997

Effects of benzodiazepines, sleep and sleep deprivation on vigilance and memory.

Anterograde amnesia is one of the troublesome adverse effects of the benzodiazepines, especially when they are used as tranquillizers. Interestingly, benzodiazepines also produce retrograde facilitation. In this review, a unifying hypothesis concerning both the cognitive enhancement and the cognitive decrement is discussed: the decrease in vigilance or sedative-hypnotic properties of the benzodiazepines induces a superficial type of encoding and consolidation. This is expressed in anterograde amnesia. The shallower encoding also causes less retrograde interference and retrograde facilitation is the result. In this way also the positive effect of sleep on memory is explained. In a series of experiments, this hypothesis was investigated. Anterograde amnesia and retrograde facilitation was demonstrated after benzodiazepine intake in healthy, volunteers. It was striking that amnestic effects and retrograde facilitation were most prominent when memory was tested one week after drug intake. A decrease in vigilance was also obtained by sleep deprivation and an increase by the gavage of the central stimulant methylphenidate. The latter vigilance increasing drug did not change memory aspects. Also memory effects were hardly present in sleep deprived subjects with low levels of vigilance and the performance on memory tests were not changed. This jeopardizes the vigilance hypothesis of the memory effects of the benzodiazepines. However, amnesia under the influence of benzodiazepines was less for semantic related words than for unrelated words. This suggests that information might be stored without appropriate contextual cues. Only under special circumstances this information can be retrieved. It is further speculated that this storage costs less efforts leading to less retrograde interference and consequently retrograde facilitation.

Amnesia↗