David F. Dinges, PhD - US grants

This program of research is concerned with the effects of hypnosis and self-hypnosis on clinically relevant psychobiologic processes. Five projects concern the effects of hypnosis on emotional, behavioral, psychoimmunological, and sleep responses to stress and pain. Project 1 seeks to document that hypnosis can alter the effects of a specific life stressor on psychological distress and immune function. Projects 2A and 2B prospectively study the effects of self-hypnosis for controlling unpredictable acute pain due to vaso-occlusive crises in children and adults who suffer from sickle cell disease. Project 3 addresses the role of hypnosis in the treatment of pain in patients with fibromyalgia syndrome, and the relationship of fibromyalgia with abnormal sleep patterns and immune function. Sleep disturbance is a common feature of response to stress and sleep is often associated with recovery from illness. Project 4 focuses on the link between sleep, sleep loss and immune function. The second major focus is on the relationship of hypnosis to dissociative aspects of sleep. Project 5 evaluates whether hypnosis can be used to create physiological sleepiness in an effort to shed light on "pathological" sleepiness. Projects 6A and 6B investigate the relationship between dissociative aspects of hypnosis and dissociative aspects of sleep (parasomnias). 6A examines the role of psychopathology, while 6B explores parasomnias and hypnotizability in healthy children and adults. Projects 7 and 8 study specific dissociative features of parasomnias. The overall coordination of the program is managed through five cores (hypnosis, sleep, and immune assessments, data analyses, administration). The clinically relevant phenomena on which the program focuses necessarily require a multidisciplinary team of active collaborators, including psychologists, psychiatrists, immunologists, rheumatologists, hematologists, and sleep psychophysiologists. The overall aim is to study the effect of cognitive processes on psychobiologic systems that are relevant to physical and mental health.

[unreadable] DESCRIPTION (provided by applicant): This project is focused on determining how best to use sleep as an intervention to promote recovery from the biobehavioral risks posed by chronic sleep restriction. Chronic partial sleep loss due to medical conditions and social demands is common and associated with significant clinical morbidity. Our studies have shown that chronic restriction of sleep to between 4h and 6h per night results in neurobehavioral deficits that accumulate to levels equivalent to those produced by total sleep loss. We will undertake the first research to determine what aspects of sleep are critical for recuperation from the effects of chronic partial sleep loss. The issue of recovery of waking neurobehavioral and physiological functions will be addressed using an experimental approach that systematically determines the recovery potential of sleep in 180 healthy female (n=90) and male (n=90) subjects. Sleep duration will be varied parametrically on two consecutive nights, following 5 days of chronic sleep restriction. Key aspects of waking biobehavioral functions sensitive to sleep loss will be measured in subjects randomized to one of six sleep durations on recovery night 1 and one of six sleep durations on recovery night 2 (i.e., a total of 36 different combinations of sleep across the two nights). Statistically efficient response-surface modeling and dose-response regression approaches will be used for mapping recovery in neurocognitive, mood, and physiological outcomes as a function of sleep, using time in bed, total sleep time, and specific sleep physiological measures (e.g., REM sleep, slow wave energy in non- REM sleep) as independent variables. The resulting response-surface maps and dose-response curves will reveal the degree of recuperation of biobehavioral functions relative to varying amounts and types of sleep. These approaches also provide estimates of the variance attributable to gender differences, age effects, and differences in habitual sleep duration at home. The empirically estimated response-surface maps will be compared to predictions inferred from current biomathematical models of sleep-wake regulation, to assess how well these models predict recovery gained from sleep of different durations. In addition to providing the first dose-response curves for the relationship of sleep duration to recovery of waking functions, this project will explore the effects of varying sleep durations on cardiovascular markers in both women and men. The scientific data to be generated will advance theoretical understanding of sleep homeostasis; improve mathematical models of sleep-wake regulation; and inform questions of sleep need relative to public health. [unreadable] [unreadable]

Nasal continuous positive airway pressure (CPAP) is the nonsurgical treatment of choice for obstructive sleep apnea syndrome (OSAS). Its efficacy for eliminating apneas and hypopneas is well established, but there continue to be significant questions about the consequences for daytime functioning of regular vs. irregular CPAP use. This project addresses these clinical issues, building on results from our two recent studies. In the first, a microprocessor-monitor inside the CPAP machines of 35 OSAS patients revealed that only 46% of them actually used CPAP regularly (more than or equal to 4 hrs/night on more than or equal to 70% of nights). Compared to irregular CPAP users, regular users were more likely to report post-treatment improvements in daytime energy, suggesting that CPAP use may be associated with the magnitude of improvement in hypersomnolence experienced by patients. Protocol I is designed to test the hypothesis that regular CPAP use results in significant improvements in objective measures of daytime sleepiness relative to irregular use. However, we do not expect regular CPAP use to yield daytime functioning comparable to that of age-and sex-matched controls, because in a second study we found that CPAP significantly improved objective and subjective measures of daytime sleepiness, but the level of functioning appeared to be suboptimal, and as soon as CPAP was withdrawn, hypersomnolence returned to pre-treatment levels. Therefore, Protocol II will determine whether the residual sleepiness present when patients are using CPAP regularly vs. irregularly is the result of an inadequate sleep duration. Because we believe that most of the residual sleepiness of regular CPAP users is due to inadequate sleep durations, we hypothesize that they will be able to extend their sleep on CPAP and this will eliminate their residual daytime sleepiness relative to that after a typical night of CPAP use. On the other hand, we expect that sleep extension with CPAP use will have less of an effect on the hypersomnolence of irregular users. This prediction is based on our view that irregular users of CPAP are a heterogeneous group, made up of patients who cannot extend sleep on CPAP, as well as those who cannot derive benefits from doing so. Therefore a subgoal of Protocol II is to determine the proportion of irregular users who do not benefit from extended sleep on CPAP. Thus we seek to answer basic clinical questions regarding the effectiveness of CPAP for relieving hypersomnolence, relative to the regularity of its use and the duration of sleep when it is used. Such answers should improve our ability to effectively treat OSAS patients. We also seek to continue to refine the techniques we have developed for assessment of CPAP use, ambulatory motility, daytime vigilance, mood, and functional status, which will be needed for future studies on the epidemiology and natural history of OSAS and its treatment.

Cumulative sleep deprivation commonly results from operational demands involving transmeridian flights, night missions, and sustained operations. Our recent studies of both acute total sleep deprivation (TSD) and cumulative partial sleep deprivation (PSD) demonstrate that as sleep loss escalates, the temporal profiles of declining alertness and performance degradation reflect the influence of both the circadian pacemaker and the homeostatic sleep drive, but the interaction between the two processes is nonlinear in ways not predicted by current models of alertness. We propose to conduct an experiment simulating deployments that produce severe TSD or cumulative PSD in order to: (1) specify the contributions (and interactions) of circadian and homeostatic processes to neurobehavioral functions during sleep loss; (2) evaluate the effectiveness of caffeine as a countermeasure to the neurobehavioral deficits produced by sleep deprivation; and (3) assess the role of recovery sleep duration in normalization of waking functions following varying degrees of sleep deprivation.

The purpose of this study is to determine how the performance on various reaction time and thinking tasks, sleepiness and mood, brain wave activity, body temperature, blood hormone levels are affected by limiting the nightly sleep. Sleep loss is common in modern society, and we want to test theories about how adult men and women respond to extended periods of curtailed sleep. We want to gather information on sleep, waking brain waves, body temperature, blood hormones, and performance patterns during 13 24-hour periods (13 days) in the GCRC at the Hospital of the University of Pennsylvania or the Clinical Neuro-Diagnostic Unit at the Hospital of the University of Pennsylvania where total sleep hours are controlled.

Cumulative sleep deprivation commonly results from operational demands involving transmeridian flights, night missions, and sustained operations. Our recent studies of both acute total sleep deprivation (TSD) and cumulative partial sleep deprivation (PSD) demonstrate that as sleep loss escalates, the temporal profiles of declining alertness and performance degradation reflect the influence of both the circadian pacemaker and the homeostatic sleep drive, but the interaction between the two processes is nonlinear in ways not predicted by current models of alertness. We are conducting an experiemnt simulating deployments that produce severe TSD or cumulative PSD in order to: (1) specify the contributions (and interactions) of circadian and homeostatic processes to neurobehavioral functions during sleep loss (88 hr total sleep loss vs. 2 hr naps every 12 hr for 88 hrs; (2) evaluate the effectiveness of sustained, low dose 0l3 mg/kg) caffeine (versus placebo) as a countermeasure to the neurobehavioral devicits produced by sleep deprivation; and (3) assess the role of recovery sleep duration (7hr vs 14 hr) in normalization of waking functions following varying degrees of sleep deprivation.

human therapy evaluation; sleep deprivation; psychic activity level; central nervous system stimulants; drug screening /evaluation; circadian rhythms; clinical research; electroencephalography; human subject;

human therapy evaluation; neuropeptide receptor; sedative /hypnotic; neuropharmacologic agent; sleep disorders; drug screening /evaluation; chemotherapy; substance P; polysomnography; human subject; clinical research;

human therapy evaluation; neuropharmacologic agent; drug screening /evaluation; chemotherapy; sleep disorders; neuropeptide receptor; substance P; human old age (65+); clinical research; human subject;

therapy design /development; neuropsychology; sleep; sleep deprivation; cognition; melatonin; cortisol; extraterrestrial environment; somatotropin; behavioral /social science research tag; human subject; clinical research;

neuropsychology; wakefulness; attention; central nervous system stimulants; melatonin; neuroendocrine system; norepinephrine; cortisol; polysomnography; behavioral /social science research tag; human subject; electroencephalography; questionnaires; clinical research;