Biomedical subjects

W C Dement

Publications and source records attributed to W C Dement.

At least 163 records · Page 9Linked to original sources

PubMed1985

A circadian rhythm of hippocampal theta activity in the mouse.

Hippocampal theta activity dominates the cortical EEG of the mouse during certain behaviors. We have therefore been able to study the circadian distribution of hippocampal theta activity by means of chronic EEG implantation and computerized EEG state scoring. Observations in six mice indicate consistent and significant circadian patterns of theta-dominated EEG, both during wakefulness (theta-dominated wake, or TDW) and during sleep (REM sleep). The probability of REM rises gradually to a maximum during the sleep period and then falls abruptly at activity onset and then falls gradually. The complementary circadian patterns of REM and TDW suggest that they may be two episodes of each coincide remarkably, as do their circadian distributions. The probability of TDW rises to a very high level at activity onset and then falls gradually. The complementary circadian patterns of REM and TDW suggest that they may be two halves of a single circadian rhythm of theta probability. This concept would be relevant in interpreting the abnormally phase-advanced pattern of REM sleep observed in human depressives.

Animals↗

PubMed1985

Sleep loss in elderly volunteers.

Sleep, performance, and sleepiness were assessed in 10 elderly volunteers (8 women, 2 men; aged 61-77 years) before, during, and after 38 h of sleep loss. Recovery night 1 sleep showed increased total sleep and stages 3 and 4 sleep and decreased stage 1 sleep, wakefulness, brief arousals, and latency to stages 3 and 4 sleep. An increase in stage 4 sleep persisted to the second recovery night. Increased arousal threshold was suggested by a lengthening of respiratory events and a reduction in arousals associated with leg movements. Performance was impaired during sleep loss, associated with an increased tendency to fall asleep. Reported sleepiness increased, except in three subjects who denied sleepiness. Latency to sleep onset declined. All measures returned to basal values after a night of sleep. Sleep in one volunteer failed to respond to sleep loss. With this exception, the response was similar to that reported in younger volunteers, although shorter-lived.

Aged↗

PubMed1985

Circadian rhythms of sleep and wakefulness in mice: analysis using long-term automated recording of sleep.

Circadian rhythms of wheel-running activity and polygraphically defined wakefulness, rapid-eye-movement (REM) sleep and non-REM (NREM) sleep were continuously observed in ten mice (Mus musculus) under both alternating light-dark (LD 12:12) and continuous darkness (DD) conditions. Sleep-wake state was determined automatically using a computer-based method that allowed continuous recordings of from 60 to 280 days in duration. The sleep-wake state percentages (of the circadian cycle) thus obtained were in substantial agreement with other estimates for this or similar strains and showed no significant difference between LD 12:12 (wake 54.3%, NREM sleep 38.1%, REM sleep 7.6%) and DD (wake 53.1%, NREM sleep 39.9%, REM sleep 7.0%) conditions. All 10 mice exhibited clear circadian rhythms in each of the three states and wheel-running activity under both lighting conditions for the entire duration of observation. Probability functions, computed using stationary sections of data from all 10 mice, showed distinct waveforms for all three states and wheel running. These waveforms were remarkably similar under entrained and free-running conditions. This documentation of sustained circadian rhythmicity in sleep-wake state throughout observations of unprecedented length contradicts the currently common assertion that circadian control of sleep state is weaker than that of activity.

Animals↗

PubMed1984

Treatment of a 12-hour shift of sleep schedule with benzodiazepines.

Normal sleepers underwent sleep recordings and daytime tests of sleep tendency, performance, and mood while being shifted 180 degrees in their sleep-wake schedule. After two baseline 24-hour periods, subjects postponed sleep until noon. For the next three 24-hour periods, they were in bed from 1200 to 2000 and received triazolam, flurazepam, or placebo at bedtime in parallel groups. Placebo subjects showed significant sleep loss after the shift. Active medication reversed this sleep loss. Despite good sleep, flurazepam subjects appeared most impaired of the three groups on objective assessments of waking function; triazolam subjects were least impaired.

Adult↗

PubMed1984

Narcolepsy: cholinergic receptor changes in an animal model.

An inbred colony of narcoleptic doberman pinschers has been analyzed for muscarinic receptor levels in 19 discrete brain regions. In comparison to age-matched controls, receptors were generally elevated in the brainstem and reduced in forebrain areas. No changes in receptor binding affinity were detected. The increased receptor levels found in the brainstem suggest that cholinoceptive neurons in this region are hypersensitive and may be involved in the initiation of cataplexy and other aspects of the narcolepsy syndrome.

Animals↗

PubMed1984

Sleep-wakefulness patterns in the aged cat.

This investigation compared the 24 h sleep-wake characteristics of young adult (2-4 years) and old (10-11 years) cats in order to determine whether there were significant age- and/or gender-related differences. Aged animals had more brief (6-14 sec) awakenings, less REM sleep, and more NREM sleep than young adults. There were no significant age- or gender-related differences with respect to either the daily numbers or the mean durations of sleep and waking episodes. Compared with the young adults, aged males had substantially less DSWS and fewer numbers of short-duration (less than or equal to 2.5 min) LSWS bouts. Both males and females showed age-related differences with respect to the sequencing of state-patterns. The expression of these patterns in relation to time of day was comparable for young and old animals. Overall, these findings compare favorably with those commonly reported in the elderly human.

Age Factors↗

PubMed1984

Rapid eye movement sleep and its relationship to feeding behavior in the adult cat.

The aim of this study was to corroborate a previous report that, in cats kept on a 12:12-hr light-dark schedule, there is a highly significant negative correlation between the quantity of REM sleep in a 12-hr period and food intake in the subsequent 12-hr interval. Analyses of sleep-wake and food intake measures from freely behaving adult cats failed to disclose any consistent correlations between food consumption and REM sleep quantities in the same or adjacent 12-hr periods; amounts of waking (or total sleep) and slow-wave sleep also showed no consistent relationship to food intake. These findings question assertions that REM sleep participates directly in regulating the expression of motivated behaviors.

Animals↗

PubMed1984

Daytime alertness in relation to mood, performance, and nocturnal sleep in chronic insomniacs and noncomplaining sleepers.

Nocturnal sleep was recorded prior to daytime testing that included the Multiple Sleep Latency Test, profile of mood states, card sorting, and Stanford Sleepiness Scale in 138 volunteers with the complaint of chronic insomnia and 89 noncomplaining sleepers ("normals"). In both groups daytime sleep tendency had no significant linear correlation either with any Minnesota Multiphasic Personality Inventory scale or with tension/anxiety and other moods assessed in the morning. In normals, speed of card sorting but not subjective sleepiness tended to correlate with sleep tendency. Given that physiological sleepiness is the most predictable consequence of sleep deprivation in normals, it is particularly interesting that 14% of the insomniac group are chronic insomniacs with no measurable daytime sleep tendency. Despite this lack of sleep tendency during the day, their nocturnal sleep was just as poor as insomniacs with greater daytime sleep tendency. The lack of daytime sleepiness seen in this subgroup may reflect a basic pathophysiological aspect of their insomnia.

Adult↗

PubMed1984

Electroencephalogram during sleep in the cat: age effects on slow-wave activity.

In humans there is a substantial decline in NREM electroencephalographic (EEG) slow-wave activity with advancing age. The present findings show that similar age-related EEG changes occur in the cat. Slow-wave (0.5-4.0 Hz) EEG activity during NREM sleep was compared in six young adult (2-4 years) and six aged (10-12 years) cats of either sex. Computer measures of slow-wave incidence and amplitude disclosed significant age- and gender-related differences. Although old male and female animals were of comparable age, only males showed significant EEG alterations. These consisted of an attenuation of slow-wave amplitude over posterolateral cortex and reductions in both the incidence and amplitude of slow-wave activity over sensorimotor cortex.

Aging↗

PubMed1984

Comparative hypnotic effects of flurazepam, triazolam, and placebo: a long-term simultaneous nighttime and daytime study.

We studied sleep and daytime function in insomniac patients who took either flurazepam, 30 mg, triazolam, 0.5 mg, or placebo 30 minutes before bedtime. Subjects were 21 patients with either a primary or a secondary diagnosis of chronic psychophysiological insomnia or insomnia associated with personality disorder. Seven subjects were randomly assigned to each condition. The study used a three group by 9 week, double-blind design with three nocturnal sleep recordings each week. During week 1, subjects took no capsules; week 2, subjects took placebo; weeks 3 to 7, flurazepam, triazolam, or placebo; weeks 8 and 9, placebo. Daytime tests for alertness and performance were administered during weeks 1, 3, 5, 7, and 8. Flurazepam showed hypnotic efficacy for weeks 3 to 5. Triazolam showed hypnotic activity for weeks 3 to 7. Although not significant overall, discontinuation of flurazepam produced rebound insomnia in six of seven subjects sometime during the two withdrawal weeks. The relationship between plasma concentration of desalkylflurazepam, the principal active metabolite of flurazepam, and sleep disturbance suggested that the onset of the rebound insomnia depended on the rate of drug washout. Discontinuation of triazolam produced a significant rebound insomnia on the first and second nights of drug withdrawal. Placebo subjects showed improved sleep throughout weeks 2 to 9 of the study. Daytime testing revealed significantly decreased daytime alertness and decreased performance for flurazepam subjects during weeks 3 to 7, although these effects reverted toward baseline despite continued drug administration.

Adult↗

PubMed1983

Narcolepsy: biogenic amine deficits in an animal model.

Concentrations of biogenic amine metabolites in discrete brain areas differed significantly between dogs with genetically transmitted narcolepsy and age- and breed-matched controls. Dopamine and 3,4-dihydroxyphenylacetic acid were consistently elevated in the brains of narcoleptic animals, while homovanillic acid was not. Narcoleptic animals consistently exhibited lower utilization of dopamine and higher intraneuronal degradation of dopamine but no uniform decrease in serotonin utilization. Hence neuropathology appears to be associated with genetically transmitted canine narcolepsy. The data indicate a nonglobal depression of dopamine utilization or turnover or both.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1983

Sleep spindle and delta changes during chronic use of a short-acting and a long-acting benzodiazepine hypnotic.

Twenty-one medically screened insomniacs were studied over 59 nights in a double-blind, parallel groups design study. The 7 patients receiving a short-acting (triazolam) and the 7 receiving a long-acting (flurazepam) benzodiazepine hypnotic showed a similar pattern and magnitude of sleep EEG changes, especially during the latter part of the 37-night treatment period. Both groups significantly increased sleep spindle rate and decreased delta count per minute. The patterns of withdrawal were also similar. Plasma levels of N-desalkylflurazepam were not significantly related to the magnitude of EEG changes.

Adult↗

PubMed1983

Nightly variation in sleep-related respiratory disturbance in older adults.

This study investigated variation in respiratory disturbance during sleep. Sixty-six healthy elderly subjects (mean age = 67.2) underwent two consecutive nights of polysomnography. Respiratory disturbance was assessed by Respiratory Disturbance Index (RDI), the number of events per hour of sleep. Results indicated an increase in RDI from Night 1 to Night 2. Fourteen subjects increased their RDI by over 2.5, and eight by over 5.0, events per hour on Night 2. The increase was not a function of increased REM on Night 2. Age was positively related to RDI on individual lab nights but unrelated to nightly variation in RDI. Subjects without complaints of insomnia were more likely to show increases in RDI, perhaps reflecting the sounder sleep of this group on the second laboratory night. This study suggests that a single night of polysomnography is likely to underestimate the absolute level of respiratory disturbance seen in a subsequent recording night. Studies placing prevalence of such disturbance in the elderly at approximately 30% are thus likely to be underestimates. Whether this "error" is important will depend ultimately upon the meaning of various absolute levels of respiratory disturbance in healthy older persons.

Adult↗

PubMed1983

Rational basis for the use of sleeping pills.

The diagnosis and treatment of insomnia is a major clinical issue. This is because the complaint of insomnia is highly prevalent and because the various clinical and laboratory manifestations of insomnia are complex. In addition, insomnia involves both day and night. This paper attempts to provide a rational framework for the evaluation of insomnia and the use of sleeping pills. Insomnia is defined and described with special attention to differentiating the subjective complaint and the laboratory assessment of objective sleep parameters. Specific disorders causing or associated with sleep disturbance and the complaint of insomnia are described, and some data bearing on relative prevalence of specific disorders are presented. Consideration of sleeping pills involves the evaluation of hypnotic efficacy as a property of the medication on the one hand and the practical clinical application on the other. Properties of different hypnotics are reviewed, including factors that affect the use of hypnotics in clinical practice. It is concluded that the rational use of sleeping pills demands a systematic approach to the evaluation of the individual patient and a specific attempt to formulate individual treatment goals together with a knowledgeable consideration of the specific chemotherapeutic agent to be utilized.

Anxiety↗

PubMed1982

[Sleep disorders and what underlies them].

This paper will have 3 purposes: --To describe some new concepts about how the physiology of normal sleep provides the substrates for sleep pathology. --To outline new approaches to daytime sleepiness as the key result of nocturnal sleep disturbance. --To outline the gamut of currently known sleep pathologies. The author concludes that somnology, clinical specialty of sleep disorders will lead the way in devising and testing specific treatment and in establishing rational indications for providing symptomatic relief with sedative/hypnotics. It seems likely that polysomnographic diagnosis will become much more widespread and that G.P.'s will want to refer their patients to a sleep disorders center to obtain evaluation and treatment recommendations.

Animals↗

PubMed1982

Motoneuron properties during electromyogram pauses in sleep.

Electrophysiological antecedents to electromyogram pauses of NREM sleep were studied intracellularly in hindlimb motoneurons. Phasic-event-related hyperpolarizing potentials (PRHP) were 0.2-7.1 mV in amplitude and 9-90 ms in duration, and coincided with dorsal neck EMG pauses and PGO waves. Motoneurons, if spontaneously discharging, were silenced during PRHPs. The discharge rate of spike trains elicited by depolarizing current reduced during PRHPs. Membrane conductance measurements indicated that PRHPs did not arise simply from soma inhibition but from either presynaptic inhibition or conductance changes in electrically-remote dendrites. EMG pauses, which normally occur spontaneously, could be evoked by stimulation of low threshold fibers in peripheral nerves. PRHPs were most prevalent in REM sleep. We concluded that EMG pauses are generated by the same cholinergic brainstem mechanism that generates spino-bulbo-spinal presynaptic inhibition of group Ia afferents. The pauses resemble the inhibitory phase of startle responses, providing evidence for the hypothesis that startle responses are spontaneously elicited in NREM and REM sleep.

Animals↗

PubMed1982

Monoamine metabolite concentrations in the cerebrospinal fluid of normal and narcoleptic dogs.

Because of the similarity between human and canine narcolepsy, an animal model has emerged with which to investigate the neurochemical basis of the disease. In this study, in vivo differences in cerebral neurotransmitter function between normal and affected dogs were measured by comparing, before and after probenecid administration, the concentrations in cisternal cerebrospinal fluid of the monoamine metabolites 5-hydroxyindoleacetic acid, homovanillic acid, 3,4-dihydroxyphenylacetic acid, and 3-methoxy-4-hydroxyphenylethylene glycol. Cisternal cerebrospinal fluid was collected from the cisterna magna of anaesthetized animals, and samples were analyzed for the metabolites and probenecid using combined gas chromatography-mass spectrometry. The concentrations of both the conjugated and non-conjugated forms of each of the metabolites were determined in all samples and the role of conjugation in cerebral monoamine metabolism is discussed. Before probenecid treatment, comparisons of metabolite concentrations in samples from normal versus narcoleptic dogs showed significantly lower amounts of the dopamine and of the 5-hydroxytryptamine metabolites in CSF from the affected animals. After probenecid administration, the concentrations in the CSF of all the metabolites increased. However, the amounts of 5-hydroxyindoleacetic acid, and the norepinephrine metabolite 3-methoxy-4-hydroxyphenylethylene glycol, in samples from narcoleptic dogs were significantly lower than those found in samples from normal dogs. The implications of these results for our understanding of the neurochemical basis of REM sleep initiation and for treatment of narcolepsy/cataplexy are discussed.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1982

Distribution of norepinephrine, epinephrine, dopamine, serotonin, 3,4-dihydroxyphenylacetic acid, homovanillic acid and 5-hydroxyindole-3-acetic acid in dog brain.

The distribution and endogenous concentrations of norepinephrine, epinephrine, dopamine, serotonin, 3,4-dihydroxyphenylacetic acid, homovanillic acid and 5-hydroxyindole-3-acetic acid were determined in the brains of adult dogs. Norepinephrine and epinephrine were localized primarily in 'central core' areas in brain stem and hypothalamus. Dopamine (DA) and its major metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acids (HVA), were localized primarily in basal ganglia with relatively high concentrations also found in amygdala, septum and substantia nigra. HVA was also found in relatively high concentrations in areas where DA concentrations was very low. Serotonin and 5-hydroxyindole-3-acetic acid levels were highest in brain stem, hypothalamus, globus pallidus and nucleus accumbens. Epinephrine levels were higher than in previously studied species, at times as much as 25-30% of norepinephrine and frequently greater than dopamine in brain stem and hypothalamus. Using the ratios 5-hydroxyindole-3-acetic acid/serotonin and homovanillic acid/dopamine as indicators of serotonin and dopamine turnover and utilization, both putative transmitters were found to be generally more highly utilized in areas of lower concentration, especially in brain stem and cortex. Catecholamines were found to be unconjugated in dog brain. DOPAC and HVA were found to exist primarily in the unconjugated form. DOPAC was found to be slightly conjugated in most areas while 10-20% of HVA was present in the conjugated form in most cases.

3,4-Dihydroxyphenylacetic Acid↗