James K. Wyatt

Psychophysiological insomnia: The behavioural model and a neurocognitive perspective

A number of paradoxes are apparent in the assessment and treatment of psychophysiological insomnia and sleep state misperception. Three of these paradoxes exist as discrepancies between polysomnographic (PSG) measures and the subjective impressions regarding sleep quality and quantity. The remaining incongruity exists largely within the objective domain. In the case of subjective–objective discrepancies, patients with insomnia: (1) frequently identify themselves as having been awake when awakened from PSG defined sleep; (2) tend to overestimate sleep latency and underestimate total sleep time as compared with PSG measures; (3) appear to derive more benefit from pharmacotherapy that can be explained by objective gains. The remaining paradox pertains to the observation that hypnotic medications, by and large, do not normalize sleep architecture or produce a more ‘sleep‐like’ EEG. In this paper, we review possible explanations for these various paradoxes, introduce a new perspective and suggest possible research avenues. The model introduced is based on the observation that beta and/or gamma activity (which have been found to be associated with cognitive processes) is enhanced in insomnia at or around sleep onset. We propose that this kind of high frequency EEG activity may interfere with the normal establishment of sleep onset‐related mesograde amnesia. As a result, the patient with insomnia maintains a level of information and/or memory processing that blurs the phenomenological distinction between sleep and wakefulness and influences retrospective judgments about sleep initiation and duration.

Circadian temperature and melatonin rhythms, sleep, and neurobehavioral function in humans living on a 20-h day

The interaction of homeostatic and circadian processes in the regulation of waking neurobehavioral functions and sleep was studied in six healthy young subjects. Subjects were scheduled to 15-24 repetitions of a 20-h rest/activity cycle, resulting in desynchrony between the sleep-wake cycle and the circadian rhythms of body temperature and melatonin. The circadian components of cognitive throughput, short-term memory, alertness, psychomotor vigilance, and sleep disruption were at peak levels near the temperature maximum, shortly before melatonin secretion onset. These measures exhibited their circadian nadir at or shortly after the temperature minimum, which in turn was shortly after the melatonin maximum. Neurobehavioral measures showed impairment toward the end of the 13-h 20-min scheduled wake episodes. This wake-dependent deterioration of neurobehavioral functions can be offset by the circadian drive for wakefulness, which peaks in the latter half of the habitual waking day during entrainment. The data demonstrate the exquisite sensitivity of many neurobehavioral functions to circadian phase and the accumulation of homeostatic drive for sleep.

EEG and ocular correlates of circadian melatonin phase and human performance decrements during sleep loss.

The aim of this study was to quantify the associations between slow eye movements (SEMs), eye blink rate, waking electroencephalogram (EEG) power density, neurobehavioral performance, and the circadian rhythm of plasma melatonin in a cohort of 10 healthy men during up to 32 h of sustained wakefulness. The time course of neurobehavioral performance was characterized by fairly stable levels throughout the first 16 h of wakefulness followed by deterioration during the phase of melatonin secretion. This deterioration was closely associated with an increase in SEMs. Frontal low-frequency EEG activity (1-7 Hz) exhibited a prominent increase with time awake and little circadian modulation. EEG alpha activity exhibited circadian modulation. The dynamics of SEMs and EEG activity were phase locked to changes in neurobehavioral performance and lagged the plasma melatonin rhythm. The data indicate that frontal areas of the brain are more susceptible to sleep loss than occipital areas. Frontal EEG activity and ocular parameters may be used to monitor and predict changes in neurobehavioral performance associated with sleep loss and circadian misalignment.

Sex difference in the near-24-hour intrinsic period of the human circadian timing system

The circadian rhythms of melatonin and body temperature are set to an earlier hour in women than in men, even when the women and men maintain nearly identical and consistent bedtimes and wake times. Moreover, women tend to wake up earlier than men and exhibit a greater preference for morning activities than men. Although the neurobiological mechanism underlying this sex difference in circadian alignment is unknown, multiple studies in nonhuman animals have demonstrated a sex difference in circadian period that could account for such a difference in circadian alignment between women and men. Whether a sex difference in intrinsic circadian period in humans underlies the difference in circadian alignment between men and women is unknown. We analyzed precise estimates of intrinsic circadian period collected from 157 individuals (52 women, 105 men; aged 18–74 y) studied in a month-long inpatient protocol designed to minimize confounding influences on circadian period estimation. Overall, the average intrinsic period of the melatonin and temperature rhythms in this population was very close to 24 h [24.15 ± 0.2 h (24 h 9 min ± 12 min)]. We further found that the intrinsic circadian period was significantly shorter in women [24.09 ± 0.2 h (24 h 5 min ± 12 min)] than in men [24.19 ± 0.2 h (24 h 11 min ± 12 min); P < 0.01] and that a significantly greater proportion of women have intrinsic circadian periods shorter than 24.0 h (35% vs. 14%; P < 0.01). The shorter average intrinsic circadian period observed in women may have implications for understanding sex differences in habitual sleep duration and insomnia prevalence.

Uncovering Residual Effects of Chronic Sleep Loss on Human Performance

The cumulative effects of chronic sleep loss may be overcome at certain times of day, but the residual effects of sleep deprivation profoundly degrade performance and may thereby compromise safety. More Than Beauty Sleep: Long Days Hamper Performance We all know the dangers of driving when tired; indeed, being awake for 24 hours straight can impair our abilities as much as a blood alcohol level of 0.10%. But all too often these real effects of too little sleep are dismissed with a laugh—or accepted. A careful dissection of the effects of short-term and long-term sleep restriction by Cohen et al. now shows that the situation is even worse than we thought. When chronic sleep loss is superimposed on the natural low-performance periods of our body’s 24-hour rhythm, reaction times slow to about 10 times normal, even if we got a good night’s sleep the night before—a truly hazardous situation. Because our circadian rhythms and sleep-wake cycles are usually intertwined, it has been difficult to dissect precisely their individual influences on how well we function. To independently determine the effects of circadian rhythm and those of acute and chronic sleep loss, the authors completely controlled the schedules of nine healthy volunteers for 38 days. For 21 of these days, the volunteers slept 10 hours out of every ~43-hour cycle, equivalent to about 5.6 hours of sleep per night. On this schedule, the subjects’ circadian rhythm, acute sleep deprivation (which they experienced during each of their long days), and chronic sleep restriction (which got worse and worse as the experiment went on) were all decoupled. By frequently giving the subjects a set of behavioral tests that measured reaction time, the authors were able to discern which factor had the most effect and when. Some of the results could be predicted from our own experience. For a few hours after waking from a 10-hour sleep, subjects’ performance was always normal, but it deteriorated as the ~33-hour waking day went on. But there was an additional effect of chronic sleep restriction. As the weeks of the experiment went by and the subjects’ sleep debt increased, their performance deteriorated to a greater extent each day, although it was still within normal limits just after they woke up. What was surprising was the very large effect of the circadian rhythm. When the subjects’ independently cycling internal clock was at its lowest point in the late night, it always extended reaction times, but its influence was considerably larger when the individual was experiencing acute or, especially, chronic sleep deprivation. Even more surprising was that when the internal clock was at its highest point in the late afternoon, reaction times were relatively normal despite substantial acute and chronic sleep loss. This leads to a dangerous situation in which individuals may not realize that they have a severe chronic sleep debt and a high vulnerability to sudden sleepiness a few hours later into the night. These findings translate into a warning for employers. Workers who need to remain awake for extended periods of time cannot maintain normal performance—and may not be aware of this vulnerability—if they are suffering from chronic sleep loss, especially if they are working at times during which their circadian rhythms are at a nadir. Sleep loss leads to profound performance decrements. Yet many individuals believe they adapt to chronic sleep loss or that recovery requires only a single extended sleep episode. To evaluate this, we designed a protocol whereby the durations of sleep and wake episodes were increased to 10 and 32.85 hours, respectively, to yield a reduced sleep-to-wake ratio of 1:3.3. These sleep and wake episodes were distributed across all circadian phases, enabling measurement of the effects of acute and chronic sleep loss at different times of the circadian day and night. Despite recurrent acute and substantial chronic sleep loss, 10-hour sleep opportunities consistently restored vigilance task performance during the first several hours of wakefulness. However, chronic sleep loss markedly increased the rate of deterioration in performance across wakefulness, particularly during the circadian “night.” Thus, extended wake during the circadian night reveals the cumulative detrimental effects of chronic sleep loss on performance, with potential adverse health and safety consequences.

Shift work and the assessment and management of shift work disorder (SWD)

Nearly 20% of the labor force worldwide, work shifts that include work hours outside 07:00 h to 18:00 h. Shift work is common in many occupations that directly affect the health and safety of others (e.g., protective services, transportation, healthcare), whereas quality of life, health, and safety during shift work and the commute home can affect workers in any field. Increasing evidence indicates that shift-work schedules negatively influence worker physiology, health, and safety. Shift work disrupts circadian sleep and alerting cycles, resulting in disturbed daytime sleep and excessive sleepiness during the work shift. Moreover, shift workers are at risk for shift work disorder (SWD). This review focuses on shift work and the assessment and management of sleepiness and sleep disruption associated with shift work schedules and SWD. Management strategies include approaches to promote sleep, wakefulness, and adaptation of the circadian clock to the imposed work schedule. Additional studies are needed to further our understanding of the mechanisms underlying the health risks of shift work, understanding which shift workers are at most risk of SWD, to investigate treatment options that address the health and safety burdens associated with shift work and SWD, and to further develop and assess the comparative effectiveness of countermeasures and treatment options.

A randomized controlled trial of mindfulness meditation for chronic insomnia.

STUDY OBJECTIVES To evaluate the efficacy of mindfulness meditation for the treatment of chronic insomnia. DESIGN Three-arm, single-site, randomized controlled trial. SETTING Academic medical center. PARTICIPANTS Fifty-four adults with chronic insomnia. INTERVENTIONS Participants were randomized to either mindfulness-based stress reduction (MBSR), mindfulness-based therapy for insomnia (MBTI), or an eight-week self-monitoring (SM) condition. MEASUREMENTS AND RESULTS Patient-reported outcome measures were total wake time (TWT) from sleep diaries, the pre-sleep arousal scale (PSAS), measuring a prominent waking correlate of insomnia, and the Insomnia Severity Index (ISI) to determine remission and response as clinical endpoints. Objective sleep measures were derived from laboratory polysomnography and wrist actigraphy. Linear mixed models showed that those receiving a meditation-based intervention (MBSR or MBTI) had significantly greater reductions on TWT minutes (43.75 vs 1.09), PSAS (7.13 vs 0.16), and ISI (4.56 vs 0.06) from baseline-to-post compared to SM. Post hoc analyses revealed that each intervention was superior to SM on each of the patient-reported measures, but no significant differences were found when comparing MBSR to MBTI from baseline-to-post. From baseline to 6-month follow-up, MBTI had greater reductions in ISI scores than MBSR (P < 0.05), with the largest difference occurring at the 3-month follow-up. Remission and response rates in MBTI and MBSR were sustained from post-treatment through follow-up, with MBTI showing the highest rates of treatment remission (50%) and response (78.6%) at the 6-month follow-up. CONCLUSIONS Mindfulness meditation appears to be a viable treatment option for adults with chronic insomnia and could provide an alternative to traditional treatments for insomnia. TRIAL REGISTRATION Mindfulness-Based Approaches to Insomnia: clinicaltrials.gov, identifier: NCT00768781.

Testing the Reliability and Validity of DSM-IV-TR and ICSD-2 Insomnia Diagnoses: Results of a Multitrait-Multimethod Analysis

CONTEXT Distinctive diagnostic classification schemes for insomnia diagnoses are available, but the optimal insomnia nosology has yet to be determined. OBJECTIVES To test the reliability and validity of insomnia diagnoses listed in the American Psychiatric Associations DSM-IV-TR and the International Classification of Sleep Disorders, second edition (ICSD-2). DESIGN Multitrait-multimethod correlation design. SETTING Two collaborating university medical centers, with recruitment from January 2004 to February 2009. PARTICIPANTS A total of 352 adult volunteers (235 of whom were women) who met research diagnostic criteria for insomnia disorder. MAIN OUTCOME MEASURES Goodness-of-fit ratings of 10 DSM-IV-TR and 37 ICSD-2 insomnia diagnoses for each patient. Ratings were provided by 3 clinician pairs who used distinctive assessment methods to derive diagnostic impressions. Correlations computed within and across clinician pairs were used to test reliability and validity of diagnoses. RESULTS Findings suggested that the best-supported DSM-IV-TR insomnia categories were insomnia related to another mental disorder, insomnia due to a general medical condition, breathing-related sleep disorder, and circadian rhythm sleep disorder. The category of primary insomnia appeared to have marginal reliability and validity. The best-supported ICSD-2 categories were the insomnias due to a mental disorder and due to a medical condition, obstructive sleep apnea, restless legs syndrome, idiopathic insomnia, and circadian rhythm sleep disorder-delayed sleep phase type. Psychophysiological insomnia and inadequate sleep hygiene received much more variable support across sites, whereas the diagnosis of paradoxical insomnia was poorly supported. CONCLUSIONS Both the DSM-IV-TR and ICSD-2 provide viable insomnia diagnoses, but findings support selected subtypes from each of the 2 nosologies. Nonetheless, findings regarding the frequently used DSM-IV-TR diagnosis of primary insomnia and its related ICSD-2 subtypes suggest that their poor reliability and validity are perhaps due to significant overlap with comorbid insomnia subtypes. Therefore, alternate diagnostic paradigms should be considered for insomnia classification.

Objective but Not Subjective Short Sleep Duration Associated with Increased Risk for Hypertension in Individuals with Insomnia

STUDY OBJECTIVES To examine the relationship between hypertension prevalence in individuals with insomnia who have short total sleep duration < 6 h or sleep duration ≥ 6 h, using both objective and subjective measures of total sleep duration. METHODS Using a cross-sectional, observational design, 255 adult volunteers (n = 165 women; 64.7%) meeting current diagnostic criteria for insomnia disorder (MAge = 46.2 y, SDAge = 13.7 y) participated in this study at two large university medical centers. Two nights of polysomnography, 2 w of sleep diaries, questionnaires focused on sleep, medical, psychological, and health history, including presence/absence of hypertension were collected. Logistic regressions assessed the odds ratios of hypertension among persons with insomnia with short sleep duration < 6 h compared to persons with insomnia with a sleep duration ≥ 6 h, measured both objectively and subjectively. RESULTS Consistent with previous studies using objective total sleep duration, individuals with insomnia and short sleep duration < 6 h were associated with a 3.59 increased risk of reporting hypertension as a current medical problem as compared to individuals with insomnia with sleep duration ≥ 6 h. Increased risk for hypertension was independent of major confounding factors frequently associated with insomnia or hypertension. No significant risk was observed using subjectively determined total sleep time groups. Receiver operating characteristic curve analysis found that the best balance of sensitivity and specificity using subjective total sleep time was at a 6-h cutoff, but the area under the receiver operating characteristic curve showed low accuracy and did not have good discriminant value. CONCLUSIONS Objectively measured short sleep duration increased the odds of reporting hypertension more than threefold after adjusting for potential confounders; this relationship was not significant for subjectively measured sleep duration. This research supports emerging evidence that insomnia with objective short sleep duration is associated with an increased risk of comorbid hypertension.

Endogenous circadian control of the human autonomic nervous system

To determine if an endogenous circadian rhythmicity, independent from sleep/wake cycles, exists in autonomic nervous system (ANS) function, heart rate variability analysis of electrocardiogram R-R intervals was applied to data collected during, a 27-day forced desynchrony protocol. Results during wakefulness indicate that the circadian pacemaker may control both the sympathetic and vagal limbs of the ANS. Vagal tone was maximal during the circadian phase corresponding to the usual sleep episode (although these measurements were made in the absence of sleep) with an acrophase at 4 AM to 5 AM. Sympathoragal balance was minimal between 9 AM and 1 PM: These endogenous circadian rhythms in ANS function may contribute to mortality from cardiovascular disease and nocturnal asthma.