Dr. Goel is Research Assistant Professor of Psychology in Psychiatry and Dr. Dinges is Professor of Psychology in Psychiatry, Division of Sleep and Chronobiology, Department of Psychiatry, and Center for Sleep and Respiratory Neurobiology, University of Pennsylvania School of Medicine, Philadelphia, PA.

Sleep is not the simple thing it appears to be. Most of us think that sleep is simply restorative: we go about our day, become tired and then fall asleep at night, during which we recover our energies for the coming day, similar to a battery being recharged.

In fact, sleep is far more complex. Sleep is regulated by two different systems — the circadian (24-hour) system and the sleep-wake system — which, together, determine alertness, performance and the timing of sleep.

Circadian Rhythms and Sleep-Wake Cycles
The circadian system is controlled by an internal biological mechanism called the circadian pacemaker. Located in the brain above the optic chiasm, the circadian pacemaker is responsible for the fact that in a normal 24-hour cycle, we will sleep at night and performance and alertness will reach low points between 3:00 AM and 5:00 AM — a time when almost all of us, even confirmed night owls, tend to be asleep — and between 3:00 PM and 5:00 PM — classic siesta time in many cultures.

We experience these low points in performance and body temperature, along with a decline in arousal, alertness and motivation, as fatigue. As part of the sleep/wake system, the sleep drive is primarily responsible for the timing of sleep. The drive to sleep reaches its lowest point in the morning, at awakening, but as the day progresses the drive to sleep increases. Once we fall asleep, the sleep drive gradually decreases until we wake up.

The circadian pacemaker is responsible for the fact that in a normal 24-hour cycle, we will sleep at night and performance and alertness will reach low points between 3:00 AM and 5:00 AM...

Fatigue, alertness and performance levels are influenced by factors other than our internal circadian rhythms and sleep drive; they are affected by external factors such as the light/dark cycle, social interaction and work demands. Although the inherent rhythm of the circadian pacemaker is actually about 24.2 hours, the light/dark cycle entrains circadian rhythms to adopt a 24-hour day.

Light dramatically affects circadian rhythms, bringing them into to a stable relationship with the sleep/wake cycle. Light is also able to adjust circadian rhythms to an earlier or later time within the biological day. Aging causes changes in the regulation of circadian rhythms which disrupt sleeping patterns and impair alertness and performance.

Types of Sleep Loss
Sleep experts define sleep deprivation as either partial or total lack of sleep, whether voluntary or involuntary. Sleep deprivation can be either an acute (occasional) or a chronic lack of sleep. Partial sleep deprivation is the term used when an individual gets some, but not all, of the sleep necessary for waking alertness during the day. Partial sleep deprivation can be caused by medical conditions, sleep disorders, as well as lifestyle (e.g., shiftwork, jet lag or working overtime).

Total sleep deprivation is defined as a complete lack of sleep lasting for 16 hours or more in a healthy adult. When total sleep deprivation lasts longer than 24 hours, a divergence occurs between the sleep/wake cycle, which begins to build an escalating sleep debt, and the circadian clock, which maintains its normal cycle. The result is counterintuitive — when we remain awake for 40 hours, we will feel less sleepy at the 36-38 hour point than at the 22-24 hour point.

Fragmented Sleep
As many people know, sleep is not a continuous state; it follows a series of stages, including rapid eye movement (REM) and other types of sleep. Sleep fragmentation, a form of partial sleep deprivation, occurs when the normal progression and sequencing of sleep stages is disrupted. If sleep fragmentation is limited to a specific sleep stage, (e.g., when sleep apnea or medications disrupt a particular stage of sleep), this is called selective sleep stage deprivation.

Sleep fragmentation, a form of partial sleep deprivation, occurs when the normal progression and sequencing of sleep stages is disrupted.

The elderly are particularly prone to this kind of fragmentation and subsequent loss of sleep quality. Selective sleep stage deprivation is characterized by waking up frequently at night, difficulties falling asleep and waking up unusually early in the morning.

Sleep fragmentation is also a symptom of sleep disorders such as obstructive sleep apnea, in which patients experience repetitive nocturnal respiratory pauses that produce chronic sleep deprivation and excessive sleepiness. Narcolepsy, in which patients show recurrent episodes of irresistible sleep (or sleep attacks), cataplexy (sudden, brief, loss of muscle control in response to strong emotions such as laughter or anger), hallucinations and sleep paralysis (the inability to move while falling asleep or awakening) also produces excessive daytime sleepiness.

Parkinson's Disease can also cause daytime sleepiness (up to 45% of cases); roughly 1% of those with Parkinson's are at risk for sleep attacks.

Chronic Sleep Debt
Sleep debt, or sleep restriction,15 is a common form of partial sleep deprivation. Researchers have studied the changes that occur when sleep is steadily reduced in duration from 8 to 4 hours each day, and the effects of these changes on sleep and waking functions.

Measuring Sleep
The effects of chronic sleep restriction are evaluated using one of two tests. In one test, subjects are instructed to close their eyes and try to fall asleep while lying down, during which their sleep patterns are evaluated with a specially-designed instrument called a polysomnograph (PSG). In the other type of test, subjects are seated upright and instructed to try and remain awake. For both tests, sleep propensity is measured as the time is takes to fall asleep.Unsurprisingly, chronic shortening of nocturnal sleep increases daytime sleep propensity.

Changes in the Structure of Sleep
Sleep restriction does not affect all sleep stages equally. For example, healthy adults fell asleep more quickly and had decreased time in non-rapid eye movement (NREM) and REM sleep when restricted to 4 hours of nocturnal sleep for multiple nights, but did not show any change in NREM slow wave sleep (SWS).

How a Lack of Sleep Affects Us
More recent experiments have found clear evidence that behavioral alertness and a range of cognitive functions — including sustained attention and working memory — deteriorate when nightly sleep duration is limited to between 4 and 7 hours.

Decision-making skills — such as our ability to assess risk, assimilate changing information and revise our strategies for solving problems based on new information, among other thinking and memory skills — are negatively affected by sleep loss. In addition, fatigue and deficits from sleep loss compromise certain memory and attention functions. These include assessment of the scope of a problem based on changing or distracting information, remembering the time order of information, maintaining focus, avoiding inappropriate risks, having insight into performance deficits, avoiding dwelling on ineffective thoughts and actions, and changing behavior based on new information.

Decision-making skills — such as our ability to assess risk, assimilate changing information and revise our strategies for solving problems...are negatively affected by sleep loss.

While the effects of chronic sleep restriction seem to be similar to those of total sleep deprivation, tests show a more muted response to chronic sleep restriction, suggesting that a different mechanism may be involved.

Sleepiness, as reported and described by research subjects, is quite different during chronic sleep debt than during total sleep deprivation. While total sleep deprivation immediately increases feelings of sleepiness, fatigue and cognitive confusion, with decreases in energy and alertness, chronic sleep debt or restriction causes much subtler changes that are more likely to escape notice. After a week or more of sleep restriction, subjects were markedly impaired and less alert but rated themselves as only moderately sleepy. People frequently underestimate the impact a lack of sleep has on their ability to function and overestimate their performance readiness when sleep restricted.

Overall, these studies suggest that when people are only getting 7 hours or less sleep a night, most healthy adults' mental abilities — to make decisions or solve problems or be able to recall information - suffer. These cognitive impairments also get worse over time. Improvement only comes when adults experience a longer recovery sleep period.

Eight hours rest between work periods is inadequate. This is because people tend to use only 50-75% of rest periods to sleep. Thus, it is advisable for individuals to take longer rest breaks (e.g., 10-14 hours), so that they can get adequate recovery sleep.

Sleep Restriction: Individual Differences
Each of us differs to some degree in our sleep and circadian patterns; the same is true for our responses to sleep deprivation. In studies, sleep loss uncovers marked differences between subjects and, as sleep loss continues over time, individual differences in the degree of cognitive deficits increase markedly. Some people experience very severe impairments even with modest sleep restriction, while others show few, if any, impairments until sleep restriction reaches severe levels. This is also true of chronic partial sleep restriction.

While there is no question that responses to sleep deprivation are stable and reliable within individuals, the reasons for this are not known.

Chronic Sleep Deprivation in the "Real World"
Some jobs require shifting work schedules and irregular sleep/wake cycles. These shifts cause misalignment between circadian rhythms and the sleep/wake cycle. The results can include increased sleep disruption, feelings of malaise, performance errors, uncontrollable falling asleep during waking hours, negative moods and problems with social interaction, inefficient communication and accidents. Any occupation that requires workers to maintain high levels of alertness over extended periods of time is vulnerable to the consequences of sleep loss and circadian disruption. For obvious reasons, this can compromise safety.

Driving is a prime example of how a lack of sleep affects real-world functioning. Studies have primarily focused on the effects of short-term sleep restriction on driving ability and the risk of accidents. One study found that sleep-related crashes rose in drivers reporting an average of less than 7 hours of sleep per night. Other factors that contributed to crashes included poor sleep quality or duration, daytime sleepiness, previous episodes of driving while drowsy, long periods of driving and driving late at night. Individuals who work irregular schedules are also more likely to drive at night, thus increasing the chances of drowsy driving and decreasing their ability to respond correctly to emergency situations; both factors result in an increase in sleep-related crashes.

Sleep deprivation affects physical coordination and reaction time in a way that is very similar to excessive alcohol consumption. Sleepiness-related motor vehicle crashes are on par with alcohol-related crashes in terms of their fatality rate and likelihood of injury. Drowsy driving is a particular problem for truck drivers. Fatigue is considered to be a factor in 20-40% of heavy truck crashes.

The Night Shift: What 24/7 Means to Your Sleep
Night work, irregular or prolonged work schedules, and shift work disrupt a person's internal, natural circadian clock and, consequently, their sleep and waking cycles. People who work at night come home and are faced with competing time cues: they are tired and ready to start winding down, but most other members are just getting started with the day. Thus, they often have trouble adapting to their work-rest schedule.

Night shift work is particularly disruptive to sleep. Many of the 6 million full-time employees in the U.S. who work at night on a permanent or rotating basis experience daytime sleep disruption leading to sleep loss and nighttime sleepiness on the job. More than 50% of shift workers complain of shortened or disrupted sleep and overall tiredness, with total amounts of sleep loss ranging from 2 to 4 hours per night. This kind of sleep loss affects the productivity and performance of shift workers.

Jet Lag
Most of us have experienced the disruption of our sleep-wake cycles that is known as jet lag. Fatigue associated with jet lag is a major concern in aviation, particularly with travel across time zones. Flight crews often experience disrupted circadian rhythms and sleep loss. Studies have documented episodes of fatigue and uncontrolled sleep (microsleeps) in pilots. Flight crew members tend to remain at their destination for a short period of time and therefore do not adjust physiologically to a new time zone and altered work schedule before they embark upon another assignment, further compounding their risk for fatigue.

The severity of jet lag also depends on the direction of travel. Normally, eastward travel is more difficult to adjust to than westward travel...

Although remaining at the new destination for a while after crossing time zones is beneficial, it does not guarantee that a person's sleep-wake cycle and circadian system will adapt quickly to a new time zone and light-dark cycle. Usually, passengers, pilots and flight crew arrive at a new destination with an accumulated sleep debt. As a result, the first night of sleep in the new time zone will occur without incident — even if it is cut short by a wake-up signal from the circadian clock. However, on subsequent nights, most people will find it more difficult to stay asleep as a result of circadian rhythm disruption. As a consequence, individuals have increasing difficulty maintaining alertness during the daytime. These cumulative effects are incapacitating and often take more than a week to go away.

The severity of jet lag also depends on the direction of travel. Normally, eastward travel is more difficult to adjust to than westward travel because it advances the circadian clock, while westward transit causes a delay. Since the human internal clock is slightly longer than 24 hours, lengthening a day is easier to adjust to physiologically and behaviorally than shortening a day by the same amount of time. Adjustment to either eastward or westward phase shifts often requires at least a 24-hour period for each time zone crossed (e.g., crossing six time zones can require 5-7 days), assuming proper daily exposure to the new light-dark cycle. Regardless of the direction individuals fly, if there is inadequate time to adjust physiologically to the new time zone, the cumulative sleep debt flight of crews and passengers will develop across days and waking performance deficits will accumulate.

The Case of Medical Professionals
Our modern health care system requires that physicians, nurses and other health care providers often need to be awake at night and work for durations well in excess of 12 hours. Chronic partial sleep deprivation is an inherent consequence of such schedules. Not surprisingly, human error increases with such prolonged work schedules. Studies have also shown that such schedules are tied to an increased likelihood of motor vehicle accidents for health care providers driving home from their shifts.

In 2003, the Accreditation Council for Graduate Medical Education (ACGME) imposed duty hour limits for residents. These limited residents to an 80 hour workweek and limited continuous duty periods to 24-30 hours. The ACGME also mandated that 1 out of every 7 days be free from duty, averaged over a 4-week period, and mandated 10-hour rest breaks between duty periods.

Treatments for Sleep Deprivation
Clearly, travel across time zones, prolonged work hours and work environments with irregular schedules contribute to performance problems, fatigue and safety risks. What can a person do to counteract sleep deprivation? The obvious best countermeasure for sleep deprivation is to get adequate sleep. Research suggests that the definition of what constitutes "adequate" varies from person to person.

Individuals who are sleep-deprived because of their work or travel schedules should make sure they give themselves prolonged, restorative sleep in the form of 10 to 14 hours of recovery sleep whenever they can.

A number of treatments are available for individuals who are unable to obtain adequate sleep because of medical or sleep-related conditions (e.g., narcolepsy, obstructive sleep apnea). These include:

Continuous Positive Airway Pressure
Continuous Positive Airway Pressure (CPAP) uses a machine to increase air pressure in your throat so that your airway does not collapse when you breathe in. It is considered the most effective treatment for obstructive sleep apnea in both middle-aged and older adults. CPAP increases alertness and improves cognitive processing, memory and executive function.

In some patients, CPAP does not completely eliminate excessive sleepiness. For them, the stimulant drug, modafinil improves vigilance, general productivity and activity level. In addition, modafinil is effective in the treatment of narcolepsy and excessive daytime sleepiness caused by Parkinson's Disease.

Caffeine improves alertness and vigilance, with the size of the effects increasing with caffeine dose, and is as effective as modafinil. Caffeine can block sleep inertia — the grogginess and disorientation that a person experiences after awakening from sleep — a fact which may explain why this common stimulant is so often used in the morning, after a night of sleep.

Bright Light
Exposure to bright light produces significant improvement in performance and alertness levels. Light wavelength appears to play a role in such improvements. For example, in one experiment, people exposed to lower-frequency (460-nm) light had significantly lower subjective sleepiness ratings and fewer attention failures than people exposed to higher-frequency (555-nm) light. In addition, light enhanced recovery from the circadian and sleep misalignments that result from jet lag, shiftwork and aging.

Fatigue, sleepiness and general performance decline — including attention lapses, increased reaction times, cognitive slowing and memory difficulties — are caused by acute and chronic sleep loss and circadian displacement of sleep-wake schedules. These are common occurrences in cases where people work unusual schedules or have sleep disorders, jet lag or certain medical conditions. They increase the likelihood of cognitive errors and the risk of mistakes or accidents, although the degree of these effects varies from one person to another. Neurobehavioral and neurobiological research have demonstrated that waking functions depend upon stable alertness and that alertness, in turn, depends on adequate daily recovery sleep. Understanding and mitigating the risks imposed by physiologically-based variations in fatigue and alertness are essential for making jobs such as driving trucks, flying airplanes or practicing medicine safer, as well as for the development of effective countermeasures.