Healthy Good Sleepers Research Articles

Residual effects of zopiclone 7.5 mg on highway driving performance in insomnia patients and healthy controls: a placebo controlled crossover study

RationaleResidual effects of hypnotics on driving performance have been mainly determined in studies using a standardized driving test with healthy good sleepers. Responses to effects may differ, however, between insomniacs and healthy volunteers due to the underlying sleep disorder. In addition, a majority of insomniacs uses hypnotics chronically resulting in the development of tolerance to impairing effects. Impaired driving performance in healthy volunteers may then be an overestimation of the actual effects in insomniacs.ObjectivesThe present study aims to compare the residual effects of zopiclone 7.5 mg on on-the-road driving performance of 16 middle-aged insomniacs chronically using hypnotics (chronic users), 16 middle-aged insomniacs not or infrequently using hypnotics (infrequent users), and 16 healthy, age matched, good sleepers (controls).MethodsThe study was conducted according to a 3 × 2 double-blind, placebo controlled crossover design, with three groups and two treatment conditions. Treatments were single oral doses of zopiclone 7.5 mg and placebo administered at bedtime (2330 hours). Between 10 and 11 h after administration subjects performed a standardized highway driving test.ResultsZopiclone 7.5 mg significantly impaired on-the-road driving performance in both insomnia groups and healthy controls. The magnitude of impairment was significantly less in the chronic users group as compared with the controls.ConclusionsThe smaller magnitude of effects suggests that investigating residual effects of hypnotics in healthy volunteers may yield a minor overestimation of the actual effects in insomnia patients.

Reduced anterior internal capsule white matter integrity in primary insomnia.

Chronic insomnia is one of the most prevalent central nervous system diseases, however, its neurobiology is poorly understood. Up to now, nothing is known about the integrity of white matter tracts in insomnia patients. In this study, diffusion tensor imaging (DTI) was used in a well-characterized sample of primary insomnia (PI) patients and good sleeper controls to fill this void. Voxelwise between-group comparisons of fractional anisotropy (FA) were performed in 24 PI patients (10 males; 14 females; 42.7 ± 14.5 years) and 35 healthy good sleepers (15 males; 20 females; 40.1 ± 9.1 years) with age and sex as covariates. PI patients showed reduced FA values within the right anterior internal capsule and a trend for reduced FA values in the left anterior internal capsule. The results suggest that insomnia is associated with a reduced integrity of white matter tracts in the anterior internal capsule indicating that disturbed fronto-subcortical connectivity may be a cause or consequence of the disorder.

Sleep-Related Arousal Versus General Cognitive Arousal in Primary Insomnia

The present study aimed at further investigating trait aspects of sleep-related cognitive arousal and general cognitive arousal and their association with both objective and subjective sleep parameters in primary insomnia patients. A clinical sample of 182 primary insomnia patients and 54 healthy controls was investigated using 2 nights of polysomnography, subjective sleep variables, and a questionnaire on sleep-related and general cognitive arousal. Compared to healthy controls, primary insomnia patients showed both more sleep-related and general cognitive arousal. Furthermore, sleep-related cognitive arousal was closely associated with measures of sleep-onset and sleep-maintenance problems, while general cognitive arousal was not. Cognitive-behavioral treatment for insomnia might benefit from dedicating more effort to psychological interventions that are able to reduce sleep-related cognitive arousal.

The relation between striatal dopamine D2/D3 receptor availability and sleep quality in healthy adults

Increasing evidence, primarily from animal studies and patients with compromised neurotransmitter systems, indicates a possibly important role for dopamine in modulating sleep. We therefore conducted this study to explore the relation between sleep and dopamine in healthy adults. We used the Pittsburgh Sleep Quality Index (PSQI) to assess sleep quality. Higher PSQI scores indicate a lower quality of sleep. Striatal dopamine D2/D3 receptor availability was determined using [123I]iodo-benzamide (IBZM) SPECT. Fifty-five healthy volunteers (32 men, 23 women; mean age, 36.7+/-12.1 years), including 25 good sleepers and 30 poor sleepers, were recruited. We analysed the correlation between the PSQI and D2/D3 receptor availability in good and poor sleepers based on Pearson's product-moment after removing the effects of gender and age. We also analysed differences in D2/D3 receptor availability between good and poor sleepers. In poor sleepers, there was no statistically significant relationship between the global, individual components of the PSQI score and D2/D3 receptor availability. However, in good sleepers, the score of the sleep duration component was significantly negatively correlated with D2/D3 receptor availability in the caudate. There was no significant difference in D2/D3 receptor availability between good and poor sleepers. Our findings demonstrate that healthy good sleepers with higher D2/D3 receptor availability in the caudate sleep longer. Poor sleep in healthy subjects might be not primarily related to the dopaminergic system.

Exercise and sleep

The belief that exercise improves sleep is common among the general population, the media, and sleep research authorities. Although epidemiologic research has consistently documented an association between exercise and improved sleep quality, experimental evidence that exercise promotes sleep has been less compelling. Studies involving acute and chronic exercise have revealed, at best, modest improvements in sleep quality that have primarily been relegated to subjective reports. However, early research was plagued by utilization of healthy good sleepers as participants, greatly limiting the possible improvement in sleep that could be induced by exercise. Fortunately, more recent research has focused on older adults and individuals with sleep disorders, with more promising results. This article reviews the available research on exercise and sleep among epidemiologic, acute, and chronic exercise training studies and discusses the possible mechanisms by which exercise could improve sleep.

Subjective and objective measures of insomnia in the context of traumatic brain injury: A preliminary study

Background and purpose To compare subjective and objective measures of sleep in traumatic brain injury patients (TBI) suffering from insomnia and in controls. Patients and methods Fourteen patients with mild to severe TBI were compared to 14 healthy good sleepers. Subjective measures of insomnia were obtained from a sleep diary (morning questionnaire), and objective measures from two nights of polysomnography (PSG). Results All subjective measures of sleep revealed significant sleep disturbance in the TBI group. TBI patients with insomnia have a tendency to overestimate their sleep disturbance compared to PSG measures of sleep. With PSG, 10 out of 14 participants with TBI could be defined as having objective insomnia. Nonetheless, when groups were compared, no significant differences were found on sleep continuity variables, although large effect sizes were seen for several measures suggesting sleep fragmentation. In terms of sleep architecture, no significant differences were found in the percentage of stage 2, slow-wave (stages 3 and 4), and rapid eye movement (REM) sleep, but a higher proportion of stage 1 sleep was found in the TBI participants. When patients using psychotropic medication were excluded, TBI patients were found to have more awakenings lasting longer than 5 min and a shorter REM sleep latency. Conclusions These results are similar to those found in patients with either primary insomnia or insomnia related to depression.

Functional imaging of the sleeping brain: review of findings and implications for the study of insomnia

Despite the growing literature indicating that insomnia is prevalent and a substantial risk factor for medical and psychiatric morbidity, the pathophysiology of both Primary and Secondary Insomnia is poorly understood. Multiple trait and state factors are thought to give rise to and/or moderate illness severity in insomnia, but 'hyperarousal' is widely believed to be the final common pathway of the disorder. To date, very little work has been undertaken using functional imaging to explore the CNS correlates, underpinnings, or consequences of hyperarousal as it occurs in Primary Insomnia. In fact, all but one of the extant studies have been of healthy good sleepers or subjects with Secondary Insomnia. In the present article, we: (1) review the studies that have been undertaken in good sleepers and in patients using functional neuroimaging methodologies, and (2) discuss how these data can inform a research agenda aimed at describing the neuropathophysiology of insomnia.

Acute finger temperature changes preceding sleep onsets over a 45-h period.

A resurgence in the field of sleep initiation and thermoregulation has seen a number of investigators reporting relatively gradual increases in distal skin temperatures of the hands and feet prior to sleep onset at typical bedtimes. The present study extends upon prior knowledge by investigating whether: (1) this is a change of distal skin temperature triggered specifically by the attempt to fall asleep and (2) whether this relationship holds for various phases of the circadian rhythm whenever sleep is attempted. Fourteen healthy good sleepers participated in a modified 45-h constant routine (CR) with multiple sleep onset latency tests (MSLT) conducted every half hour. After a brief decrease of finger temperature associated with small postural adjustments at the beginning of each sleep latency test, finger temperature showed rapid (0.8 degrees C min-1) increases of 1-3 degrees C leading up to the onset of sleep. This rapid increase of finger temperature was relatively consistent across the 45-h CR, despite very significant circadian variation of the pre-MSLT baseline finger temperature and homeostatic decrease of sleep latency.

Neuroimaging of NREM Sleep in Primary Insomnia: A Tc-99-HMPAO Single Photon Emission Computed Tomography Study

The objectives of this study were to: 1) demonstrate the feasibility of combining polysomnography and SPECT neuroimaging to study NREM sleep in primary insomnia and 2) evaluate possible functional CNS abnormalities associated with insomnia. Patients with insomnia and good sleeper controls were studied polysomnographically for three nights with a whole brain SPECT Scan of NREM sleep on Night 3. Groups were screened for medical/psychiatric history, substance use, and matched on age, body mass index, and education. Sleep Research Laboratory and Nuclear Medicine Center Nine females, 5 patients with chronic psychophysiologic insomnia and 4 healthy good sleepers (mean age 36 years, SD 12, range 27-55). N/A. Tomographs of regional cerebral blood flow during the 1st NREM sleep cycle were successfully obtained. Contrary to our expectations, patients with insomnia showed a consistent pattern of hypoperfusion across all 8 pre-selected regions of interest, with particular deactivation in the basal ganglia (p=.006). The frontal medial, occipital, and parietal cortices also showed significant decreases in blood flow compared to good sleepers (p<.05). Subjects with insomnia had decreased activity in the basal ganglia relative to the frontal lateral cortex, frontal medial cortex, thalamus, occipital and parietal cortices (p<.05). This study demonstrated the feasibility of combining neuroimaging and polysomnography to study cerebral activity in chronic insomnia. These preliminary results suggest that primary insomnia may be associated with abnormal central nervous system activity during NREM sleep that is particularly linked to basal ganglia dysfunction.

Urinary 6-sulfatoxymelatonin cycle-to-cycle variability.

For either clinical or research purposes, the timing of the nocturnal onset in production of the urinary melatonin metabolite 6-sulfatoxymelatonin (UaMT6s-onset), has been proposed as a reliable and robust marker of circadian phase. However, given that most circadian rhythms show cycle-to-cycle variability, the statistical reliability of phase estimates obtained from a single study using UaMT6s-onset remains to be determined. Following 2 weeks of sleep diary and wrist actigraphy, 15 young, healthy good sleepers participated in four UaMT6s sampling sessions spaced 1 day apart. During the sampling sessions subjects remained indoors under low light conditions and hourly urine samples were collected from 19:00 to 02:00 h. Samples were subsequently assayed for UaMT6s using standard radioimmunographic techniques. UaMT6s-onset was determined by the time at which melatonin production exceeded the average of three proceeding trials by 100%. Sleep onset times were derived from sleep diary and actigraphic measures taken before the melatonin collection nights. We found that there was no significant variation between nights in group mean UaMT6s-onset times, and intraindividual variability was small. In addition, UaMT6s-onset times were highly and significantly correlated between nights (grand mean r = 0.804). Our results suggest that within 95% confidence interval limits, individual UaMT6s-onset estimates obtained from a single night UaMT6s-onset study can be used to predict subsequent UaMT6s-onset times within +/- 97 min. A close temporal relationship was also found between the timing of UaMT6s-onset and sleep onset. Overall, our results suggest that under entrained conditions single-session UaMT6s-onset studies can provide reliable individual UaMT6s-onset phase estimates and that the protocol described in this study is a practical and noninvasive methodology.

Early rising or delayed bedtime: which is better for a short night's sleep?

The present study compares the effects on sleep and the subsequent period of wakefulness of delaying bedtime of 2 h or advancing rising time by 2 h in subjects clearly differentiated by morningness or eveningness in their circadian rhythms. Twelve young healthy good sleepers, six morning types (MT) and six evening types (ET), were selected. The data obtained from the second 24 h (night and day) with delayed bedtime (DB) and advanced rising time (AR) were compared with those obtained in the reference condition (R) with normal sleep schedules. Sleep was recorded polygraphically and rectal temperature was continuously monitored during the nights and during the day following the second night of each condition. Subjective estimations of alertness, performance tasks and urinary steroids were analysed. Early rising appeared to be more disturbing than a late bedtime. The second shortened night showed fewer characteristics of recovery sleep in AR than in DB. The decrease in self rated alertness was a function both of the type of condition (DB or AR) and of the morning-evening typology of the subject. The largest decrease was observed in AR and in the ET subjects. AR also resulted in the most pronounced decrease in performance tasks and in an increase in urinary 17 ketosteroids without changes in the 17 hydroxy-corticosteroids. The effects on rectal temperature were limited to short periods after bedtime in DB and rising time in AR.