Slow Wave Sleep Measures Research Articles

Evidence That Homeostatic Sleep Regulation Depends on Ambient Lighting Conditions during Wakefulness.

We examined whether ambient lighting conditions during extended wakefulness modulate the homeostatic response to sleep loss as indexed by. slow wave sleep (SWS) and electroencephalographic (EEG) slow-wave activity (SWA) in healthy young and older volunteers. Thirty-eight young and older participants underwent 40 hours of extended wakefulness [i.e., sleep deprivation (SD)] once under dim light (DL: 8 lux, 2800 K), and once under either white light (WL: 250 lux, 2800 K) or blue-enriched white light (BL: 250 lux, 9000 K) exposure. Subjective sleepiness was assessed hourly and polysomnography was quantified during the baseline night prior to the 40-h SD and during the subsequent recovery night. Both the young and older participants responded with a higher homeostatic sleep response to 40-h SD after WL and BL than after DL. This was indexed by a significantly faster intra-night accumulation of SWS and a significantly higher response in relative EEG SWA during the recovery night after WL and BL than after DL for both age groups. No significant differences were observed between the WL and BL condition for these two particular SWS and SWA measures. Subjective sleepiness ratings during the 40-h SD were significantly reduced under both WL and BL compared to DL, but were not significantly associated with markers of sleep homeostasis in both age groups. Our data indicate that not only the duration of prior wakefulness, but also the experienced illuminance during wakefulness affects homeostatic sleep regulation in humans. Thus, working extended hours under low illuminance may negatively impact subsequent sleep intensity in humans.

Reduced Slow-Wave Sleep Is Associated with High Cerebrospinal Fluid Aβ42 Levels in Cognitively Normal Elderly.

Emerging evidence suggests a role for sleep in contributing to the progression of Alzheimer disease (AD). Slow wave sleep (SWS) is the stage during which synaptic activity is minimal and clearance of neuronal metabolites is high, making it an ideal state to regulate levels of amyloid beta (Aβ). We thus aimed to examine relationships between concentrations of Aβ42 in the cerebrospinal fluid (CSF) and measures of SWS in cognitively normal elderly subjects. Thirty-six subjects underwent a clinical and cognitive assessment, a structural MRI, a morning to early afternoon lumbar puncture, and nocturnal polysomnography. Correlations and linear regression analyses were used to assess for associations between CSF Aβ42 levels and measures of SWS controlling for potential confounders. Resulting models were compared to each other using ordinary least squared linear regression analysis. Additionally, the participant sample was dichotomized into "high" and "low" Aβ42 groups to compare SWS bout length using survival analyses. A significant inverse correlation was found between CSF Aβ42 levels, SWS duration and other SWS characteristics. Collectively, total SWA in the frontal lead was the best predictor of reduced CSF Aβ42 levels when controlling for age and ApoE status. Total sleep time, time spent in NREM1, NREM2, or REM sleep were not correlated with CSF Aβ42. In cognitively normal elderly, reduced and fragmented SWS is associated with increases in CSF Aβ42, suggesting that disturbed sleep might drive an increase in soluble brain Aβ levels prior to amyloid deposition.

Disturbances in slow-wave sleep are induced by models of bilateral inflammation, neuropathic, and postoperative pain, but not osteoarthritic pain in rats

Preclinical assessment of pain has typically relied on measuring animal responses to evoked stimulation. Because of inherent limitations of these assays, there is a need to develop measures of animal pain/discomfort that are objective, not experimentally evoked, and mimic the human condition. Patients with chronic pain manifest a variety of co-morbidities, one of which is disturbances in sleep. We used electroencephalography to objectively assess 4 rat models of pain (inflammatory/complete Freund’s adjuvant [CFA], neuropathic/chronic constriction injury [CCI], postoperative/skin incision, osteoarthritis/monosodium iodoacetate [MIA]) for the occurrence of sleep disturbances. Four different measures of slow-wave sleep (SWS) were examined: amplitude of 1- to 4-Hz waves, total time spent in SWS, time spent in SWS-1, and time spent in SWS-2. Bilateral injuries were more likely to induce a sleep disturbance than unilateral injuries in the CFA, CCI, and skin incision assays. Sleep disturbances occurred in the deeper stage of SWS, as the amplitude of 1- to 4-Hz waves and time spent in SWS-2 were significantly decreased in all models except the osteoarthritis model. Sleep disturbances lasted for approximately 3 to 14days, depending on the model, and were resolved despite continued hypersensitivity to evoked stimulation. Morphine, gabapentin, diclofenac, and ABT-102 (TRPV1 antagonist) all improved sleep in the bilateral CFA assay at doses that did not significantly alter SWS in uninjured rats. Preclinical assessment of compounds should follow the path of clinical studies and take into account diverse aspects of the “pain condition.” This would include evaluating nociceptive thresholds as well as other endpoints, such as cognition and sleep, that may be affected by the pathological state.

Enhanced slow wave sleep and improved sleep maintenance after gaboxadol administration during seven nights of exposure to a traffic noise model of transient insomnia

Slow wave sleep (SWS) has been reported to correlate with sleep maintenance, but whether pharmacological enhancement of SWS also leads to improved sleep maintenance is not known. Here we evaluate the time-course of the effects of gaboxadol, an extra-synaptic gamma-aminobutyric acid (GABA) agonist, on SWS, sleep maintenance, and other sleep measures in a traffic noise model of transient insomnia. After a placebo run-in, 101 healthy subjects (20-78 y) were randomized to gaboxadol (n = 50; 15 mg in subjects <65 y and 10 mg in subjects ≥65 y) or placebo (n = 51) for 7 nights (N1-N7). The model caused some disruption of sleep initiation and maintenance, with greatest effects on N1. Compared with placebo, gaboxadol increased SWS and slow wave activity throughout N1 to N7 (p < 0.05). Gaboxadol reduced latency to persistent sleep overall (N1-N7) by 4.5 min and on N1 by 11 min (both p < 0.05). Gaboxadol increased total sleep time (TST) overall by 16 min (p < 0.001) and on N1 by 38 min (p < 0.0001). Under gaboxadol, wakefulness after sleep onset was reduced by 11 min overall (p < 0.01) and by 29 min on N1 (p < 0.0001), and poly-somnographic awakenings were reduced on N1 (p < 0.05). Gaboxadol reduced self-reported sleep onset latency overall and on N1 (both p < 0.05) and increased self-reported TST overall (p < 0.05) and on N1 (p < 0.01). Subjective sleep quality improved overall (p < 0.01) and on N1 (p < 0.0001). Increases in SWS correlated with objective and subjective measures of sleep maintenance and subjective sleep quality under placebo and gaboxadol (p < 0.05). Gaboxadol enhanced SWS and reduced the disruptive effects of noise on sleep initiation and maintenance.

Sleep correlates of cognition in early course psychotic disorders

Background Slow waves and sleep spindles, the main oscillations during non-rapid eye movement sleep, have been thought to be related to cognitive processes, and are impaired in psychotic disorders. Cognitive impairments, seen early in the course of psychotic disorders, may be related to alterations in these oscillations, but few studies have examined this relationship. Method Twenty seven untreated patients with a recently diagnosed psychotic disorder had polysomnographic sleep studies and neuro-cognitive testing. Results Reduced power in the sigma range, which reflects spindle density, was associated with impaired attention, and reasoning, but not intelligence quotient (IQ). Slow wave sleep measures were not significantly associated with any cognitive measures. Conclusions Impairments in sleep spindles may be associated with cognitive deficits in the early course of psychotic disorders. These observations may help clarify neuro-biologic mechanisms of cognitive deficits in psychotic disorders such as schizophrenia.

The Nightly Use of Sodium Oxybate Is Associated with a Reduction in Nocturnal Sleep Disruption: A Double-Blind, Placebo-Controlled Study in Patients with Narcolepsy

To further explore the effects of sodium oxybate (SXB) administration on nocturnal sleep in narcolepsy patients during a double-blind, placebo-controlled, parallel group study conducted with 228 adult patients with narcolepsy/cataplexy in the United States, Canada, and Europe. Patients were withdrawn from antidepressants and sedative/hypnotics, and then randomized to receive 4.5, 6, or 9 g SXB or placebo nightly for 8 weeks. Patients receiving 6 and 9 g/night doses were titrated to their final dose in weekly 1.5 g increments, while patients receiving placebo were randomized to undergo a similar mock dose titration. The use of stimulant therapy continued unchanged. Changes in sleep architecture were measured using centrally scored nocturnal polysomnograms. Daily diaries were used to record changes in narcolepsy symptoms and adverse events. Following 8 weeks of SXB treatment, study patients demonstrated significant dose-related increases in the duration of stage 3 and 4 sleep, reaching a median increase of 52.5 minutes in patients receiving 9 g nightly. Compared to placebo-treated patients, delta power was significantly increased in all dose groups. Stage 1 sleep and the frequency of nocturnal awakenings were each significantly decreased at the 6 and 9 g/night doses. The changes in nocturnal sleep coincided with significant decreases in the severity and frequency of narcolepsy symptoms. The nightly administration of SXB to narcolepsy patients significantly impacts measures of slow wave sleep, wake after sleep onset, awakenings, total sleep time, and stage 1 sleep in a dose-related manner. The frequency and severity of narcolepsy symptoms decreased with treatment.

Effects of adolescent ethanol exposure on sleep in adult rats

Although adolescent ethanol (EtOH) exposure has been associated with long-lasting changes in brain function, little is known as to whether EtOH exposure during adolescence alters sleep and cortical arousal. This study examined protracted alterations in sleep in adult rats exposed to EtOH during adolescence. Adolescent male Wistar rats were exposed to EtOH vapor for 12 h/day for 5 weeks. Cortical electroencephalograms were obtained during 4-h recording sessions after 5 weeks of withdrawal from EtOH. Adolescent EtOH exposure significantly reduced the mean duration of slow-wave sleep (SWS) episodes and the total amount of time spent in SWS in EtOH-exposed rats, compared to controls. Spectral analysis revealed that adolescent EtOH exposure significantly increased cortical peak frequencies during SWS in the 2–4, 4–6, and 6–8 Hz bands. Taken together, our findings suggest that chronic EtOH exposure in adolescent rats reduces measures of SWS, an effect also seen as part of normal aging. Although the cellular and molecular mechanisms mediating the consequences of EtOH exposure on the aging process are not known, the similarities between adolescent EtOH exposure and aging merits further investigation.

Effect of Gaboxadol on Sleep in Adult and Elderly Patients with Primary Insomnia: Results From Two Randomized, Placebo-Controlled, 30-Night Polysomnography Studies

To evaluate the efficacy and tolerability of gaboxadol in the treatment of adult and elderly patients with primary insomnia. Randomized, double-blind, placebo-controlled, multicenter, 30-night, polysomnography studies. Sleep laboratory. Primary insomnia, 18-64 y (adult study), or > or =65 y (elderly study). Adult study: gaboxadol 15 mg (GBX15; N = 148), 10 mg (GBX10; N = 154), or placebo (N = 156); elderly study: GBX10 (N = 157), gaboxadol 5 mg (GBX5; N = 153), or placebo (N=176). Primary endpoints were wake after sleep onset (WASO) and latency to persistent sleep (LPS). Slow wave sleep (SWS) was a secondary endpoint. Analyses were based on the change from baseline for the average of nights 1/2, and nights 29/30, and compared gaboxadol versus placebo. Exploratory endpoints included patient's subjective assessment of total sleep time (sTST), WASO (sWASO), time to sleep onset (sTSO), and number of awakenings (sNAW); these analyses were based on weekly means. 1) Adult study. GBX15 significantly (P < or = 0.05) improved WASO through nights 29/30 but had no significant effects on LPS. No significant differences were seen for GBX10 versus placebo on WASO or LPS. GBX15 and GBX10 enhanced SWS. GBX15 significantly improved sTST, sWASO, sTSO, and sNAW at weeks 1 and 4. 2) Elderly study. GBX10 significantly improved WASO through nights 29/30; a significant improvement was also seen for GBX5 at nights 1/2 but this was not maintained through nights 29/30. GBX10 significantly improved LPS at nights 1/2 but the improvement was not maintained through nights 29/30; no significant differences were seen for GBX5 versus placebo on LPS. GBX10 and GBX5 enhanced SWS. GBX10 significantly improved sTST at week 1, and sTST, sWASO, and sNAW at week 4. Gaboxadol was generally well tolerated in both studies. The maximum studied doses of gaboxadol (GBX15 in adult patients and GBX10 in elderly patients) were effective at enhancing objective polysomnography measures of sleep maintenance and SWS, and also some subjective sleep measures, over 30 nights but had little or no effects on sleep onset. The clinical relevance of the enhancement of SWS by gaboxadol is unclear.

Neuroendocrine and sleep regulation as predictors of illness course and therapy in depression

Background and Aims:In depression, changes in EEG sleep measures are well documented findings. However, the predictive value of these alterations for treatment and long-term course of depression still warrants clarification. Therefore, we examined whether the previous course of depression, treatment response during antidepressant therapy, and the long-term outcome in follow-up are associated with sleep regulation. Since the hypothalamic-pituitary-adrenocortical (HPA) system may play a crucial role in depression's neurobiology, we evaluated HPA system function as well.Methods:15 patients (4 men, 11 women; age 43–59) with depression were enrolled in the study. HPA system assessment using the combined DEX/CRH test and sleep EEG studies were conducted at baseline, after a 6 week antidepressant treatment period (trimipramine), and at follow-up, i.e., after 2-10 years.Results:The previous clinical course, i.e., the number of episodes until baseline, correlated significantly with EEG sleep measures i.e. sleep continuity values, slow wave sleep (SWS) and REM latency.During treatment sleep continuity values improved and the correlation with the previous long-term course disappeared. The correlation with SWS persisted. The only sleep EEG marker at baseline predictive for treatment response was REM latency.In the prospective long-term outcome SWS and REM density variables were related to the occurrence of recurrences. These sleep EEG markers correlated closely with HPA system regulation.Conclusions:The long-term outcome of depression is related to the sleep EEG pattern: SWS and REM density measures may reflect predictive markers for the long-term course. These markers are associated with HPA system regulation.

Slow-wave sleep and waking cognitive performance II: Findings among middle-aged adults with and without insomnia complaints

Previous studies showing a relationship between nocturnal slow-wave sleep (SWS) and subsequent diurnal performance among young normal sleepers and older insomnia sufferers have provided limited support for the notion that this sleep stage serves a restorative role for neurocognitive functioning. The current study, which examined the relationship between SWS and reaction time performance among middle-aged adults with and without insomnia complaints, was conducted to further explore this possibility. A sample of 31 noncomplaining middle-aged (ages 40 to 59 years) normal sleepers and a like-aged sample of 27 insomnia sufferers, provided data for the current investigation. All participants underwent nocturnal sleep monitoring immediately prior to undergoing a battery of daytime tests that measured simple reaction time, vigilance/signal detection, and complex reaction time. Results showed relationships between reaction time performances on some tasks and some SWS measures among both the normal sleepers and insomnia sufferers. Findings supported our prediction that the presence of sleep pathology (e.g., insomnia) alters the SWS–performance relationship observed, but the results failed to show a consistent relationship between SWS and subsequent performance within either sample. The findings suggest that the specific performance demands of the task in question as well as physiological parameters other than SWS may determine performance as well. Findings for this and previous studies do provide some support for the contention that the neurocognitive restorative value of SWS may change across the lifespan. Possible implications of the study's findings are discussed and directions for future research are considered.

Is there a relationship between delta sleep at night and afternoon cerebral blood flow, assessed by HMPAO-SPECT in depressed patients and normal control subjects? Preliminary data

We wished to explore the relationships between waking HMPAO uptake and visually scored polysomnography. We hypothesized that HMPAO activity would correlate positively with slow wave sleep measures the same night. Eight unmedicated unipolar patients with current DSM-IV major depression (17-item Hamilton Depression Rating Scale Score 21.5±2.9) and seven control subjects received polysomnography on 2 consecutive nights. On the afternoon following the adaptation night, subjects received cerebral SPECT, with 15 mCi Tc-99m-HMPAO injected while subjects performed the Continuous Performance Task. Patients and control subjects did not significantly differ on demographic, polysomnographic, and SPECT variables. Slow wave sleep measures correlated positively (Spearman's) with global and regional tracer activity for depressed ( n=8), control ( n=7) and combined groups ( n=15); in other words, the greater the global or regional afternoon HMPAO uptake, the greater the slow wave sleep measures were the same night. In addition, the greater the waking afternoon global or regional HMPAO activity, the faster subjects fell asleep and the less Stage 2% they had. In patients, global and regional HMPAO activity correlated positively with REM density. Positive correlations between waking tracer activity and subsequent slow wave measures are consistent with previous hypotheses linking slow wave sleep with brain energy conservation and restoration. Further study is needed to determine whether these functional relationships differ in depression.

Slow-wave sleep and symptomatology in schizophrenia and related psychotic disorders

Deficits in slow-wave sleep (SWS), or delta sleep, are frequently seen in schizophrenia, but their relation with schizophrenic symptomatology remains unclear. We examined the association between visually scored and automated measures of SWS and positive and negative symptoms in a series of unmedicated patients with schizophrenia and related psychotic disorders. Total and average automated delta wave counts were significantly inversely associated with negative symptoms overall, and the psychomotor poverty syndrome in particular. Total delta counts were also inversely related to the disorganization syndrome. No relation was seen between reality distortion or the Brief Psychiatric Rating Scale (BPRS) positive symptoms and SWS. These findings support the view that SWS deficits may be related to negative symptoms of schizophrenia and may perhaps be mediated by impaired functioning of frontothalamic neural circuits.

Eeg sleep correlates of recurrence of depression on active medication

AbstractIn this study we sought to examine whether reduced slow wave sleep (delta sleep) parameters were related to the risk of recurrence of major depression in patients receiving pharmacologic maintenance treatment. The EEG sleep of 53 patients was examined on three occasions: while drug‐free during an index episode, while on imipramine at the point of stabilization of the index episode, and after 20 weeks of continuation therapy on imipramine. While a trend for total delta wave counts at the index episode evaluation was noted with time to recurrence using the Cox proportional hazards model, a stronger association was found with delta wave counts after 20 weeks of imipramine therapy (P =. 019). The intraclass correlation for the 3 time points was very high (.78) indicating that the amount of total delta sleep remained stable throughout all conditions. These findings support the notion that specific slow wave sleep measures may represent persistent or “trait‐like” abnormalities with prognostic significance in recurrent depression. Depression 1:300–308 (1993). © 1993 Wiley‐Liss, Inc.

Evidence for circadian influence on human slow wave sleep during daytime sleep episodes.

The occurrence of slow wave sleep within spontaneously initiated daytime sleep episodes was studied to examine hypothesized associations with prior wakefulness and circadian factors. There was a strong relationship between measures of slow wave sleep and the proximity of sleep episodes to the maximum of body core temperature. Those sleep episodes that began within 4 hours of the maximum in body core temperature contained significantly more slow wave sleep than did all other daytime sleep periods, approximating proportions typical of nocturnal sleep. Multiple regression analysis revealed no relationship between measures of slow wave sleep and prior wakefulness. These findings are consistent with an hypothesized approximately-12-hour rhythm in the occurrence of slow wave sleep and they underscore the influence imposed on human sleep by the endogenous circadian timing system.

Slow wave sleep in elderly depressed, demented, and healthy subjects.

The application of automated analysis in the measurement of sleep electroencephalogram delta activity allows a more precise temporal description of slow wave sleep changes in normal and pathological aging than do standard, all-night, slow wave sleep measures. Thus, with a baseline crossing technique, elderly depressives were shown to have a higher delta count per minute during the second NREM sleep period than did controls or demented subjects. This difference reflected greater activity per minute in the 2-3 Hz frequency band (75-200 microV).