SECTION 2 - RESTRICTED SLEEP: NEUROBEHAVIORAL AND PHYSIOLOGICAL EFFECTS

Sleep Deprivation in Adults

Background

Studies on the effects of sleep loss on neurobehavioral functions, especially neurocognitive performance, have two primary emphases: (a) specification of the properties of tasks (e.g., cognitive versus physical; long versus short duration) that make them sensitive to sleep loss; and (b) specification of the aspects of performance (e.g., cognitive processing speed versus accuracy, declarative versus implicit memory processes) that are impacted by sleep loss. Underlying this research has been controversy regarding the likely nature of sleep loss-induced performance deficits (e.g., whether they reflect true deficits in physiological function of the brain, a motivational effect reflecting reprioritization of the reinforcement hierarchy, an initiation of sleep onset mechanisms in the face of waking performance, or some combination of these processes). This controversy has not been resolved due to lack of a basic understanding of the function(s) of sleep, the physiological processes affecting recuperation during sleep, and the neurobiology of sleepiness.

Implicit in this research has been the assumption that total and partial sleep deprivation produce qualitatively similar decrements in brain function and/or motivation levels that differ only in degree. As a result, the overwhelming majority of studies in which the relationship between sleep and performance have been explored have utilized the more efficient total sleep deprivation procedures, and very few studies have examined the effects of chronic sleep restriction. Further, of these few studies only a very small subset have included adequate and objective verification of compliance with the sleep restriction regimen being studied.

Nevertheless, partial sleep deprivation is more pervasive than total sleep deprivation. Epidemiological studies suggest that mean sleep duration has decreased substantially as proportionally more people are awake more of the time. These decreases are due, in part, to expanded possibilities for nighttime activities that accompanied the introduction of electric light and other technologies, and to the more recent trend toward expansion of both manufacturing and service sectors to 24 hour-per-day operations. Sleep restriction appears to be an almost inevitable consequence of nighttime shift work.

Because of the scarcity of chronic sleep restriction experiments despite a wealth of total sleep deprivation/performance studies, theoretical and practical questions remain: (a) What are the physiological processes mediating neurobehavioral performance deficits resulting from sleep loss? (b) What accounts for the wide individual differences that emerge in the ability to maintain performance during s leep loss? (c) Do the physiological and neurobehavioral responses to chronic partial sleep loss differ from those resulting from total sleep loss? (d) Relative to the adverse neurocognitive and physiological effects of sleep loss, is there habituation/adaptation or potentiation/sensitization to repeated exposure to sleep loss? (e) Are there physiological and/or behavioral adaptations or dysfunctions in sleep or circadian physiology in response to chronic sleep restriction (e.g., a change in sleep itself or the brain's recovery response to chronically inadequate sleep)? (f) Are the neurobehavioral and physiological effects of chronic partial sleep loss different at different circadian phases? (g) What are the physiological processes that affect restoration of cognitive performance capacity during recovery sleep, and are these processes reflected in any currently measured sleep parameters? (h) How much recovery sleep is required following chronic partial sleep loss vs. total sleep deprivation? (i) What are the effects on neurobehavioral functions of long term (weeks, months, years) exposure to a typical work or school schedule of 5 or more days of sleep restriction followed by 2 days of recovery?

Research on sleep loss countermeasures in healthy adults, including pharmacological and non-pharmacological interventions such as napping strategies, is also of increasing practical and theoretical relevance. There is a need for experiments on the efficacy, long-term effectiveness, and safety of repeated use of traditional stimulants (e.g., caffeine, d-amphetamine, methylphenidate) and novel wake-promoting agents (e.g., modafinil) for maintenance of performance in healthy adults engaged in emergency and/or continuous operations. Complementary studies of sleep-inducing and/or phase-shifting drugs (e.g., benzodiazepine agonists, melatonin) to enhance sleep and subsequent alertness/performance (e.g., for those engaged in shift work, transmeridian travel, or recovery from continuous operations) will likewise continue to expand from the clinical to the operational realm.

Napping strategies and sleep scheduling will constitute at least part of any comprehensive strategy to maintain alertness and performance during extended continuous operations. Cell phones, beepers, and other communication devices can put some workers in a perpetual "on-call" status in which sleep might be interrupted by need for rapid decisions and/or other duty-related tasks. Studies of sleep inertia (and sleep inertia countermeasures), therefore, will be of increasing relevance and importance. Finally, the physiological effects of acute and chronic sleep loss in vital organ systems other than the brain have only just begun to be explored.

Progress In The Last 5 Years

- Functional brain imaging studies and EEG brain-mapping studies show that the patterns of functional connectivity between brain regions evident during performance of specific cognitive tasks are altered by sleep loss. This suggests that maintenance of performance during sleep loss may depend upon regional functional plasticity.

- Recent experiments have documented precise dose-response effects of chronic sleep restriction on waking neurobehavioral and physiological functions, suggesting that the cumulative waking neurocognitive deficits and state instability that develop from chronic sleep loss have a basis in a neurobiological process that can integrate homeostatic pressure for sleep across days.

- There have been increased efforts to determine the roles of REM and nonREM sleep in memory consolidation, although definitive evidence for such relationships remains elusive.

- Plasticity in visual cortices during a critical period in kittens is NREM sleep-dependent. This suggests that one function of sleep is to facilitate the functional organization of the brain, and that there are sleep-dependent aspects of putatively related processes such as LTP and DNA repair.

- Genetic array techniques have identified the patterns of gene expression that characterize and differentiate sleep and wakefulness. This information will help in understanding the most basic cellular processes mediating performance and alertness deficits following sleep loss, and the restoration of performance capacity and alertness during subsequent sleep.

- Studies have identified those aspects of performance that are most susceptible to sleep inertia, their differential time courses, and have begun to identify sleep inertia countermeasures (e.g., caffeine).

Research Recommendations

- Determine the physiological and behavioral processes mediating the state instability (manifested as increased variability in alertness and neurobehavioral performance) that result from acute versus chronic sleep loss. Compare these processes with those mediating the alertness and performance deficits that characterize pathologies such as Narcolepsy, Sleep-Disordered Breathing ( Section V), and closed head injury.

- Identify the full range of psychological, behavioral, and physiological (e.g., endocrine, immune, cardiovascular, liver, muscle, etc.) consequences of long-term cumulative partial sleep deprivation and their underlying mechanisms.

- Discover the physiological processes mediating restoration/recovery of alertness and performance by sleep. This includes elucidation of the basic mechanisms that contribute to the time course of recovery within and between days, as well as determining whether there are longer-duration time constants for reversal of the cumulative neurobehavioral deficits that accrue during chronically restricted sleep.

- Determine whether and how factors such as cognitive activity/workload and physical activity/work modulate sleepiness.

- Identify factors that account for individual differences in sleep need, and in the apparent differential vulnerability among people with similar sleep needs in their neurocognitive and physiological responses to sleep deprivation. The stability and reliability of these individual differences need to be established and, once established, a search for stable and reliable biological and behavioral predictors is needed to establish a phenotype that can then be investigated.

- Determine the physiological basis and behavioral characterization of sleep inertia effects, and study the comparative effects of possible countermeasures for sleep inertia.

- Assess the physiological modulation of sleepiness by stimulant and wake- promoting pharmacological agents, focusing on their sustained efficacy and safety for acute and chronic sleep deprivation, the impact of repeated dosing, and the effect of these agents on recovery sleep homeostasis and on the "recycle rate" (the speed with which full recovery from sleep loss is achieved, preparing the individual for initiation of another episode of sleep restriction/deprivation).