Insomnia, metabolic rate and sleep restoration.

Studies have shown occasional evidence of increased physiological activity in patients with primary insomnia. We hypothesized that metabolic rate, as measured by overall oxygen use (VO2), might be a more general index of increased physiological activity. An initial experiment found elevated VO2 both at night and during the day in patients with primary insomnia as compared with matched normal sleepers. A second experiment found significant but more modest increases in VO2 in patients with Sleep State Misperception Insomnia [who complain of poor sleep but who had normal sleep by electroencephalographic (EEG) criteria]. In a third experiment, normal young adults were given caffeine 400 mg three times per day (TID) for 1 week as a means of increasing VO2 and possibly producing other symptoms of insomnia. Participants developed many symptoms consistent with those seen in patients with primary insomnia (poor sleep, increased latency on the Multiple Sleep Latency Test, increasing fatigue despite physiological activation, and increased anxiety on the Minnesota Multiphasic Personality Inventory (MMPI)). In a final experiment, physiological arousal was again produced by caffeine to determine if sleep with elevated arousal would be less restorative. All subjects (Ss) slept for 3.5 h after being given 400 mg of caffeine. During 41 h of sleep deprivation that followed, there was no significant condition difference for the Multiple Sleep Latency Test or mood measures. The results provided only weak support for the idea that sleep is less restorative after physiological arousal.

Impact of activity and arousal upon spectral EEG parameters.

OBJECTIVE: Increased high-frequency EEG activity in patients with insomnia has been posited to reflect increased physiological activity, increased mental content, or increased muscle artifact. In the current study, the impact of physiological arousal and increased EMG upon spectral EEG measures was examined. METHODS: Thirteen normal young adults performed eyes-open and eyes-closed maneuvers in the following conditions: (1) Initial (performed immediately after calibrations); (2) following sitting up and lying down (SIT); (3) following standing up and lying down (STAND); (4) Following a 5-min walk around the building (WALK); (5) during a 5-min mental subtraction task (MATH); (6) During 1 min of gritting teeth (GRIT); and (7) During 1 min of clenching fists (CLENCH). Observations were performed during or immediately after manipulations (AROUSED) and repeated about 10 min later (RELAXED). RESULTS: Significant increases in high-frequency spectral power were found in AROUSED vs. RELAXED conditions (significant at 26, 33, 36,40-42, 44, 46, and 48-49 Hz). Larger significant increases in spectral power were seen in the GRIT condition in the range from 24 to 50 Hz and to a lesser extent in the CLENCH condition. Spectral activity during the MATH condition was similar to that in the AROUSED condition. Heart rate was significantly increased during the GRIT and CLENCH conditions. CONCLUSIONS: In this study, gritting teeth produced large changes in spectral high-frequency power in the same range as produced by the other manipulations. The most parsimonious explanation for such data is that the increased high-frequency activity associated with various forms of arousal is not a specific cortical activity. However, because heart rate was also elevated during the GRIT condition, it implies that high-frequency spectral EEG power may still be a sign of increased central nervous system arousal, although the mechanism may be through increased muscle tension.

Arousal components which differentiate the MWT from the MSLT.

STUDY OBJECTIVES: The purpose of this study was to determine the relative contribution of the instruction to maintain wakefulness versus posture change as major components determining sleep latency in the MWT as compared to the MSLT. DESIGN AND SETTING: After adaptation, subjects spent 3 nights and the following days in the laboratory. On each day, Ss had eight sleep latency measurements including four sleep latency tests from two of the following conditions: Lay down and Sleep (MSLT); Lay down and stay Awake; Sit up and Sleep; Sit up and stay Awake (MWT); and sit in a chair in front of a Computer and stay awake. PARTICIPANTS: Participants were 14 young adult normal sleepers. INTERVENTIONS: NA. MEASUREMENT AND RESULTS: Significant differences in sleep latency were found for each condition with respect to all of the others except that the Computer condition did not differ from the Sit-Awake condition. Means for conditions were: Lay-Sleep -11.1 minutes; Sit-Sleep -17.7 minutes; Lay-Awake - 21.7 minutes; Sit-Awake - 29.0 minutes; Computer - 30.1 minutes. Correlations between conditions declined as subjects sat up. CONCLUSIONS: The MWT differs from the MSLT by taking advantage of the arousal system (motivation and posture) to maintain alertness (i.e., increase sleep latency). These arousal effects are additive. MSLT results may not always correlate well with MWT results because the MWT measures the combined effects of the sleep and arousal systems while the MSLT, in ideal situations, measures only sleepiness.

Reported chronic insomnia is independent of poor sleep as measured by electroencephalography.

OBJECTIVE: Several behavioral, physiological, and subjective variables were examined in subjects reporting chronic insomnia (IN group) and subjects with no complaint of insomnia (NC group) to determine factors predictive of poor sleep as measured by electroencephalography (EEG sleep). METHODS: A total of 177 subjects (121 in the IN group and 56 in the NC group) were evaluated on the basis of EEG sleep, subjective sleep, sleepiness, performance, mood, personality, and metabolic parameters during a 36-hour laboratory stay. RESULTS: Equal percentages of subjects in each group had 0, 1, or 2 nights of poor EEG sleep, indicating that the IN group was not more likely to have impaired sleep in the laboratory. Results of the Minnesota Multiphasic Personality Inventory showed that subjects in the IN group had more pathological personality profiles, and results of laboratory studies showed that these subjects had worse mood ratings, less subjective sleepiness, poorer memory performance, and longer midafternoon sleep latencies. Subjects in the IN group also rated their laboratory sleep as poorer in quality with more time awake after sleep onset and longer sleep latencies, but no differences in EEG sleep were observed. Poor nights of EEG sleep were associated with being male, increasing age, and a history of more time awake after sleep onset; among the laboratory tests, poor EEG sleep was associated with worse mood ratings, poorer memory performance, longer sleep latencies (as indicated by higher scores on the Multiple Sleep Latency Test), higher sleep/wake ratios for metabolic parameters, lower ratings of sleep quality, and longer perceived sleep latencies. CONCLUSIONS: A history of chronic insomnia does not predict poor EEG sleep. Both chronic insomnia and poor EEG sleep are associated independently with dysphoria, hyperarousal, diminished waking function, and negative subjective sleep quality. Separate arousal and sleep systems are posited to account for these results.

Activity, arousal, and the MSLT in patients with insomnia.

OBJECTIVES: It has recently been shown that physiological arousal following walking increased sleep latencies during daytime naps as compared to sleep latencies following TV viewing. Patients with insomnia have been shown to have increased physiological arousal and to also have longer MSLT latencies. It was hypothesized that insomnia patients, who are at a higher state of physiological arousal, would be unable to relax while lying in bed and watching TV and therefore would have relatively longer sleep latencies in naps following TV watching (due to inability to relax) as compared to walking. DESIGN: Twelve patients with psychophysiological insomnia took Multiple Sleep Latency Tests after either watching television for 15 minutes or after a 5-minute walk following baseline, sleep deprivation, and recovery sleep conditions. SETTING: Sleep Laboratory PATIENTS: Twelve patients with psychophysiological insomnia INTERVENTIONS: Manipulation of state arousal and sleep deprivation RESULTS: Sleep latencies were significantly longer following the walk as compared to watching TV (11.9 vs. 6.9 min. respectively). Sleep latencies were 13.4 and 3.8 min. following baseline and sleep deprivation conditions. Heart period, used as a measure of physiological arousal, was significantly elevated throughout naps following the walk as compared to naps following TV viewing. Heart period was also significantly correlated with nap sleep latency. CONCLUSIONS: The insomnia patients in this study had significantly increased arousal, as measured by heart rate, and significantly longer sleep latencies after walking as compared to resting. The magnitude of these changes was similar to that seen in normal subjects in a previous study. These data, in concert with previous work, support the contention that measured sleep tendency is a combination of sleep drive and level of central nervous system arousal, where arousal has both state and trait components.

The impact of music upon sleep tendency as measured by the multiple sleep latency test and maintenance of wakefulness test.

Previous work has shown that background noise or music has a small positive impact on performance during sleep deprivation. The current study examined the effect of background music on the ability to fall asleep or remain awake. Twelve normal-sleeping young adults took multiple sleep latency tests (MSLT) and maintenance of wakefulness tests (MWT) after baseline sleep and one night of total sleep deprivation either with background music or under standard (quiet) conditions. It was hypothesized that the music would help maintain wakefulness both under baseline and sleep deprivation conditions. The results of the study showed that sleep latencies were increased in both MSLT and MWT when music was presented, but that this effect occurred primarily before subjects were sleep-deprived (a significant Music by Sleep Deprivation interaction). Sleep latencies were 15 and 11 min on the MSLT (33 and 26 min on the MWT) with Music as compared to Quiet after baseline sleep. Heart rate, used as a measure of physiological arousal, was significantly elevated in MWT and MSLT trials where music was presented. These data support previous work showing that level of arousal has an impact on measured sleep tendency which is independent of that of the sleep system. On a practical level, these data indicate that music may play a small beneficial role in helping to maintain arousal.

Diagnosis and treatment of insomnia.

Insomnia is an extremely common complaint. Frequently, it occurs secondary to a number of medical and psychiatric conditions that directly affect the ability to initiate or maintain sleep. Insomnia can also occur secondary to behavioral factors, such as shift work, whereby patients either do not follow or control the dictates of their internal circadian rhythm or develop inappropriate conditioned responses to their sleep surroundings. Insomnia can be a primary and even lifelong complaint. Patients with primary insomnia probably have a physiologic problem that has not been clearly identified as the basis for their subjective complaint.

The use of lorazepam TID for chronic insomnia.

Patients with primary insomnia typically complain of daytime fatigue and stress and have been shown to have long latencies on the Multiple Sleep Latency Test and increased whole body metabolism. However, typical treatment strategies for patients with insomnia rarely include any component to deal with these daytime symptoms. In the present study it was hypothesized that a 24-h treatment, lorazepam 0.5 mg TID, would be superior to an evening treatment, lorazepam 1.5 mg HS, in patients with primary insomnia. In a repeated measures crossover design, 12 patients with chronic insomnia received placebo or lorazepam 0.5 mg TID in one 4-night lab stay and placebo or lorazepam 1.5 mg HS in another lab stay. Both doses of medication were effective in improving objective and subjective measures of sleep and in reducing nocturnal whole body metabolic rate. Latencies on daytime nap testing were significantly reduced from a 14-min average to an average of 10 and 12 min, respectively, in the lorazepam 0.5 and 1.5 mg conditions. Significant differences were not found on psychomotor performance. Subjective reports of anxiety and confusion were increased in the morning after receiving lorazepam 0.5 mg in the evening but tension was reduced and subjective alertness was improved in the evening after daytime administration of lorazepam 0.5 mg. It was concluded that measurement and treatment of daytime symptoms is appropriate in patients with chronic insomnia but that rebounds in anxiety near the end of metabolic activity of lorazepam may make it a poor treatment choice.

Level of arousal and the ability to maintain wakefulness.

The ability to maintain wakefulness under baseline and sleep deprivation conditions was examined in a group of 14 normal young adults. Subjects participated in both standard and manipulation Maintenance of Wakefulness tests after being awake for 7, 19, and 31 h. In the manipulation Maintenance of Wakefulness tests, subjects performed varying degrees of physical activity at the onset of stage 1 to allow them to preserve wakefulness. As expected, ability to maintain wakefulness declined as time awake increased. With amount of time awake held constant, wakefulness was enhanced most after standing and doing knee bends, less after standing, less after sitting up, and least after subjects were spoken to. The improvement in alertness after doing knee bends as compared to being spoken to was of the same relative magnitude as the decrease in alertness after one night of total sleep deprivation. As expected, heart rate also increased consistently as activity increased. Each subject had a negative correlation between their EEG sleep latencies and their minimum r-r interval during the manipulation, i.e. the higher the heart rate, the longer the latency. These data were interpreted as a demonstration of the impact of discrete phasic arousal on the ability to maintain wakefulness.

Heart rate variability in insomniacs and matched normal sleepers.

OBJECTIVE: It was hypothesized that psychophysiological insomniacs, who have been shown to have elevated heart rate, body temperature, and whole body metabolic rate, would also have increased low frequency and decreased high frequency power in the spectral analysis of their heart period data. METHOD: Groups of 12 objectively defined insomniacs and age-, sex-, and weight-matched controls with normal sleep were evaluated on sleep and EKG measures over a 36-hour sleep laboratory stay. RESULTS: Heart period was decreased (ie, heart rate was increased) and its SD was decreased in all stages of sleep in the insomniacs compared with the controls. Spectral analysis revealed significantly increased low frequency power and decreased high frequency power in insomniacs compared with controls across all stages of sleep. CONCLUSIONS: Because increased low frequency spectral power is an indicator of increased sympathetic nervous system activity, these data imply that chronic insomniacs could be at increased risk for the development of disorders, such as coronary artery disease, that are related to increased sympathetic nervous system activity.

Sleepiness as measured by modified multiple sleep latency testing varies as a function of preceding activity.

Many studies have examined the impact of varying levels of sleep loss or sleep disturbance upon the multiple sleep latency test (MSLT). Virtually no studies have examined the impact of level of physiologic arousal upon measured sleep tendency. In the current study, 12 normal-sleeping young adults took modified multiple sleep latency tests after either watching television for 15 minutes or after a 5-minute walk. This entire protocol was repeated on another week after subjects had been partially sleep deprived by reducing their time in bed by 50%. It was hypothesized that sleep latencies would be significantly shorter after watching television as compared to walking and after partial sleep loss as compared to normal sleep and that these effects would be independent. The results of the study supported all of these hypotheses. ANOVAs showed no significant interaction effects, but sleep latencies were 11.6 and 5.8 minutes following the walk and watching television respectively. Sleep latencies were 9.8 and 7.6 minutes following baseline and partial sleep-deprivation conditions. Heart rate, used as a measure of physiological arousal, was significantly elevated throughout naps following the walk as compared to naps following television viewing. On a theoretical level, these data imply that measured sleepiness is a combination of sleep drive and physiological arousal, and these effects appear to be independent. On a practical level, these data indicate that more care may be necessary in monitoring the activity levels of patients and subjects prior to MSLT evaluations, since physiological arousal may mask the measurement of sleep tendency. Knowledge of the role of arousal in modulating sleepiness can be important in many settings.

The consequences of a week of insomnia. II: Patients with insomnia.

Insomnia patients present with a consistent set of complaints that they generally report as secondary to their poor sleep, including increased tension/confusion, decreased vigor, personality disturbance, subjective overestimation of poor sleep, increased body temperature, increased 24-hour whole-body metabolic rate, and longer MSLT latencies. If there is a relationship between the poor sleep and the secondary symptoms, then particularly poor sleep should exacerbate those symptoms. Ten patients with insomnia were identified on the basis of a 2-night screening protocol, then slept in the laboratory for 10 additional nights. On 7 of the nights, the insomnia patients had their wake-after-sleep-onset increased so that their total sleep time was 80% of that on their second screening night, resulting in an average of 254 minutes (of 480 minutes in bed) of sleep. The spectrum of changes seen in these patients with insomnia who had very poor sleep for a week was characteristic of mild partial sleep deprivation, and not consistent with exacerbation of symptoms found in patients with primary insomnia. Specifically, (1) these patients had a reduction as opposed to an increase in the MSLT values, but the MSLT values at the end of the week remained within normal limits; (2) these patients had decreased (as opposed to increased) whole metabolic rate following nights of particularly poor sleep; (3) these patients tended to underestimate (rather than overestimate) their subjective sleep latency while being given particularly poor sleep; and (4) these patients displayed no significant change in body temperature, subjective anxiety, or MMPI scores following particularly poor sleep. It was concluded that the secondary symptoms reported by patients with primary insomnia are probably not related to their poor sleep per se. Data from previous studies that varied physiological arousal were used to support the contention that the secondary symptoms of patients with insomnia, and perhaps the poor sleep itself, occur secondary to central nervous system hyperarousal.

Work schedule and task factors in upper-extremity fatigue.

We tested the combined effects of work schedule and task factors on upper-extremity fatigue in the laboratory during 8-h and 12-h shift schedules. Participants performed a simulated manual assembly task at three repetition rates and three torque loads and self-adjusted their work cycle duration to maintain fatigue at moderate levels. Work cycle durations decreased with increases in both load level and repetition rate. Fatigue was observed more quickly with increasing time on shifts and during night shifts compared with day shifts. Work schedule effects were most apparent at lighter workloads, with minimal differences at higher workloads. The highest fatigue levels were observed during 12-h night shifts, with similar levels reached by the end of both the week of 8-h night shifts and the week of 12-h day shifts. Overall durations were 20%-30% shorter than in previous short-term studies, which was likely a result of the more realistic work schedules used in this study. Results from this study could be applied to the design of work-rest schedules for manual tasks involving the upper extremities.

Physiological activation in patients with Sleep State Misperception.

OBJECTIVE: Sleep State Misperception insomnia has been commonly viewed as a perceptual or psychological problem. It was hypothesized that Sleep State Misperception insomnia, like psychophysiological insomnia, could be associated with increased physiological activation, here indexed by whole body metabolic rate. METHOD: Groups of nine patients with Sleep State Misperception insomnia and age-, sex-, and weight-matched normal sleepers were evaluated on sleep, performance, mood, personality, and metabolic measures over a 36-hour sleep laboratory stay. RESULTS: Sleep State Misperception insomniacs had a subjective history of poor sleep and perceived their laboratory sleep as poor but had electroencephalogram (EEG) parameters that did not differ statistically from matched normal controls. Sleep State Misperception insomniacs had abnormal MMPI values and were subjectively more confused, tense, depressed, and angry than matched normals. Sleep State Misperception insomniacs also had a significantly increased 24-hour metabolic rate, compared with matched normals. CONCLUSIONS: The overall increase in whole body oxygen use was less than that seen in psychophysiological insomniacs but was consistent with the view that Sleep State Misperception insomnia may be a mild version or a precursor to psychophysiological insomnia.

Heart rate variability: sleep stage, time of night, and arousal influences.

Spectral analysis was used to assess heart rate variability in consecutive 5-min epochs during the night in 12 normal adults. Simultaneous time coding of EEG and digitized EKG allowed examination of heart rate variability as a function of sleep stage, time of night and presence of EEG arousal. The results replicated previous studies in showing increases in high frequency components and decreases in low frequency components of heart rate variability across NREM sleep stages and opposite changes in REM sleep and wake. These results are consistent with sympathetic nervous system activation during REM sleep and wake periods. The shift in heart rate variability seen during REM sleep began in NREM sleep several minutes prior to standardly scored REM and often continued beyond the end of REM sleep. EEG arousals during Stage 2 and to some extent REM sleep were also associated with changes in heart rate variability which were consistent with sympathetic activation. An examination of beat to beat intervals in proximity to EEG arousals showed heart rate acceleration at least 10 beats prior to the EEG arousal. The arousal data along with Stage 2 sleep transition data support the contention that increases in central nervous system sympathetic activity precede and possibly play a role in the initiation of REM sleep and arousals during sleep.

Sleep latency measures of caffeine effects during sleep deprivation.

Studies of stimulants during sleep deprivation have used performance assessment batteries (PABs) and occasionally the multiple sleep latency test (MSLT) as measures. Another type of sleep latency test, the maintenance of wakefulness test (MWT), assesses ability to remain awake without assistance, rather than ability to go to sleep. The MWT previously has not been used in studies of stimulants during sleep deprivation. This study of caffeine during 64 h without sleep included a PAB, the MSLT, and a single MWT trial per day. The PAB and the MSLT were sensitive to caffeine effects during the first 24 h without sleep. The MWT demonstrated that caffeine improved ability to remain awake even after 2 nights of sleep deprivation. Ability to go to sleep and ability to stay awake during sleep deprivation appear to be affected differently by caffeine. PAB testing may fail to detect this stimulant effect because technicians prevent subjects from nodding off during PAB testing, an external support not available to subjects during the MWT and also not available in many real-world work environments. The MWT was more sensitive to stimulant amelioration of sleep-deprivation effects. The findings need to be validated with MWTs at other times of day and with other stimulants.

Hyperarousal and insomnia.

Primary or psychophysiological insomnia has alternatively been viewed as either a predominantly psychological problem or as a predominantly physiological problem. Several early studies of patients were not able to document physiological differences, but more recent studies have found that many patients with primary insomnia take longer than control subjects to fall asleep on daytime nap tests despite feeling fatigued and they have elevated metabolic rate throughout both night and day. Other recent studies have found that increasing physiological arousal level for a week in normal sleepers produced the major secondary symptoms reported by insomniacs. In contrast, producing the disturbed sleep of insomniacs in a group of normal sleepers did not produce the typical pattern of secondary symptoms. Taken together, evidence is presented which supports the contention that primary insomniacs suffer from a disorder of hyperarousal and that the elevated arousal produces the poor sleep and other symptoms reported by patients. It is therefore suggested that new treatment strategies directed at reduction of arousal level be considered in these patients.

The consequences of a week of insomnia.

A yoked control study used sleep recordings from 10 insomniacs to produce similar sleep patterns in a group of matched normal sleepers for 7 nights to determine if specific electroencephalographic (EEG) sleep patterns were responsible for the secondary insomnia symptoms reported by the insomniacs. Specifically, it was found that insomniacs display increased tension/confusion, decreased vigor, personality disturbance, subjective over-estimation of poor sleep, increased body temperature, increased 24-hour whole body metabolic rate, and increased multiple sleep latency test (MSLT) values. Normal sleepers given the nocturnal EEG parameters of insomniacs displayed decreased tension, decreased vigor, decreased body temperature, and decreased MSLT values. The spectrum of changes seen in the normal sleepers given an insomniac sleep pattern was characteristic of mild partial sleep deprivation and not consistent with symptoms found in patients with primary insomnia. It was concluded that the secondary symptoms reported by patients with primary insomnia are probably not related to their poor sleep per se. Data from previous studies that varied physiological arousal were used to support the contention that the secondary symptoms of insomnia, including poor sleep, occur secondary to central nervous system hyperarousal.