Sleep V: Get a good night’s sleep. It’s good for your brain! (Part 1)

INTRODUCTION

This post describes sleep’s benefits to brain functioning while the next post (Part 2) will examine the underlying neurological processes thought to provide these benefits.

Figure 1. Effects of Sleep Deprivation on the brain and body. By Mikael Häggström, used with permission.

All you have to do to demonstrate sleep’s benefits is deprive people of sleep and observe what happens.   Almost everyone has performed this “experiment” on themselves and usually find they are not at their best the next day.   The symptoms can include: moodiness/grumpiness, problems in concentrating and problem solving, problems in short-term and long-term memory, elevated blood pressure, elevated hunger, reduced balance and coordination, reduced sex drive, and suppression of the immune system.  Many of these issues are related to altered brain functioning.  After 18 hours of being awake, the average person functions as badly driving a car as someone who fails a blood-alcohol test.  Some of the effects of sleep deprivation are also illustrated in the “Wikipedia Man” of figure 1.

While most people recover from a single sleepless night without lasting effects, the effects of chronic partial deprivation are more insidious.  People who chronically sleep less than they should are more likely to have health problems as well as a shorter life span.   Although there is variation in how much sleep is needed, the “sweet spot” is typically between 7 to 8 ½ hours of sleep per night.  It is very worrying to health professionals that as much as 30% of the U.S. population get chronically insufficient sleep. Regardless of cause, chronic sleep deprivation/disruption is clearly bad for your health.   Paradoxically, sleeping longer than normal is even more strongly associated with impaired health and shortened life span.

To help insure enough sleep, a “sleep drive” is biologically programmed into our brains.  Just as your brain makes you hungry when deprived of food and thirsty when deprived of water, your brain makes you sleepy when deprived of sleep.  Our brain “understands” that being chronically sleepy is not healthy and does its best to minimize this state.  In addition to making you want to go to sleep, your sleepy brain also wants you to make up for lost sleep by sleeping more at your next opportunity.  There is some evidence that the two most important types of sleep, REM sleep and slow-wave sleep (NREM3), may have separate drives.  As will be described in the next post, REM and NREM sleep appear to benefit the brain in different ways.

Unfortunately, a significant percentage of individuals “disregard” their brain’s “wisdom” on a regular basis.

SLEEP DEPRIVATION RESEARCH.

The best way to identify sleep’s contributions to brain functioning is to deprive individuals of sleep.  However, all the different methods have limitations.   The most scientifically rigorous are human and animal experiments comparing subjects randomly assigned to sleep-deprivation conditions with those in non-deprived control conditions.  However, Human Research Ethics Committees, who pre-approve the research, limit these durations for ethical reasons.   Consequently these durations may not be sufficient to see all the consequences of extended sleep deprivation.  Institutional Animal Care and Use Committees can approve longer sleep-deprivation durations for animals.  However, unlike humans, the animals are not willing participants and the methods of keeping them awake are likely stressful.  Consequently it is not always clear whether the effects are due to lack of sleep or stress.  In addition, animal brains don’t always function the same way as human brains, so animal research may not always be relevant to humans (or even to other animal species).  Another approach is to examine the case histories of humans who, on their own, have chosen to stay awake much longer than allowed in experimental research.  However,  these case histories occur under uncontrolled conditions, making their rigor and generalizability questionable.  And finally, correlational studies find that humans who chronically sleep too little (or too much) have more health problems and reduced longevity.  However, correlational studies cannot reliably disentangle cause and effect.   

Despite these issues, all lines of research point in the same direction.  Lack of sleep is bad for brain functioning!

Experimental Studies of Human Sleep Deprivation.

Aloha & Polo-Kantola (2007) and Medic et al. (2017) reviewed the effects of sleep deprivation and disruption on cognitive and noncognitive performance in humans.   Although different studies sometimes differ in particular findings, as a whole, they overwhelmingly supported sleep’s role in supporting brain functioning. 

Much of this research focuses on decrements in cognitive performance following sleep deprivation and its relationship to other aspects of brain functioning such as attention, short-term memory, long-term memory, mood, visuomotor performance, reasoning, vigilance, emotional reactivity, decision making, risk-taking, judgement, and motivation.  In addition, sleep deprivation also adversely affects non-cognitive brain functions including increased responsiveness to stress, increased pain sensitivity, increased blood pressure, increased activity of the sympathetic nervous system, increased appetite, and disturbances in circadian rhythms.  

Both reviewers point out that sleep-deprivation experiments can sometimes be difficult to interpret because they can be affected by so many variables.  For example, some studies find that cognitive performance in sleep-deprived individuals declines only because of inattentiveness but remains normal when attentive. However, other studies find that cognitive abilities are impaired even when attentive.   These differences could be due to the nature of the cognitive task and/or the extent of the sleep deprivation.  Two other cognitive performance parameters are speed and accuracy. If the task is self-paced, some sleep-deprived individuals trade speed for accuracy.  In this case, accuracy is unaffected, the subject just takes longer.  However, the extent to which subjects employ this trade-off is affected by age, sex, as well as by individual differences.  If the cognitive task is time-constrained, both speed and accuracy are likely to be affected.  There are also many other methodological issues that must be taken into consideration in designing and interpreting sleep-deprivation experiments.

Medic (2017) points out that the inattentiveness of sleep-deprived individuals can often be explained by microsleeps lasting only a few seconds. The non-responsive individual often has a vacant stare and may have a slight head movement before returning to full awareness. Although their eyes are open, and the subjects believe they are awake, their EEG is that of NREM sleep.  Microsleeps can also occur in non-deprived individuals, particularly during lengthy, boring tasks.  Many automobile and industrial accidents, particularly late at night, are now thought to be caused by microsleeps.

Another important point is that much of the research on humans has examined acute total deprivation.  Experiments examining chronic partial deprivation, the type of greatest concern to health professionals, are less common because these experiments take longer and are more difficult and costly to perform.   The two types of sleep deprivation do have similar outcomes, but there are some differences.   Two important differences are that chronically deprived individuals are generally less aware they are impaired and recover from sleep deprivation more slowly.

Experimental Studies of Animal Sleep Deprivation.

Unlike humans, non-human animals will not voluntarily stay awake for sleep researchers.  So some procedure must be used to keep them awake.  In some of the earliest sleep-deprivation experiments in the 1800’s, dogs were kept awake by walking them whenever they attempted to go to sleep (Bentivoglio & Grassi-Zucconi, 1997). In these studies, puppies died within several days, while adults lasted between 9-17 days.  Autopsies revealed degenerative changes in both the brain and body.  Although consistent with sleep being essential for biological functioning, it is not clear whether the dogs died from from lack of sleep, exercise, or the stress involved in keeping them awake.

When modern sleep research began in the 1960’s, scientists realized that they needed to find ways to keep animals awake without over-stressing or over-exercising them (Nollet, Wisden & Franks, 2020).  Much of this research utilized rats or mice where stress could now be assessed by measuring blood concentrations of corticosterone, the main stress hormone of rodents.  Some experimenters were also able to use modern brain-wave (EEG) techniques to more precisely target their procedures.  Despite improved methods, issues of interpretation remain.

Figure 2. Disk-over-water method of sleep deprivation

Perhaps the most cited example of this line of research was performed by Rechtshaffen and his colleagues using rats (summarized in Rechtshchaffen and Bergmann, 2002).  Their method of keeping subjects awake is called the disk-over-water method. As seen in Figure 2, each experimental subject had a yoked control kept under virtually identical environmental conditions.  The subject and control rats were housed in identical chambers, perched on a circular platform that extended into each of their chambers.  Both had unlimited access to food and water and in both cases the platform was just above a pan of water.

Whenever the subject of the experiment was awake the platform was stationary, however, when the subject attempted to go to sleep, the platform began rotating.   When rotating, both the subject and yoked control needed to begin walking to keep from falling into the water.  While this procedure kept subjects continuously awake, the yoked controls could sleep whenever the platform was not moving.  In some experiments the subject was totally sleep deprived, while in other experiments, the subject was deprived only of REM sleep.

The subjects subjected to either total deprivation or REM deprivation were much more seriously impaired than their yoked controls.  The deprived subjects progressively lost weight despite eating more food than their yoked controls and developed a disheveled appearance accompanied by ulcerative lesions on their tails and paws.  Both types of deprivation affected core body temperature.   The totally deprived subjects exhibited an initial rise in core temperature for a number of days followed by a decline as the experiment progressed.  The REM-deprived rats showed only the later decline.

When sleep deprivation was allowed to continue, the totally deprived rats died in about 2-3 weeks, while the REM-sleep deprived rats died in about 4-6 weeks!  Rechtshaffen and colleagues felt these effects were from lack of sleep and discounted the role of stress or a weakening of circadian rhythms for a number of reasons.  They further argued that the impaired health and death of their subjects were caused by unsustainably high energy demands for some vital process they were unsuccessful in identifying.

Other methods have also been used to deprive animals of sleep. Animals have been kept in running wheels and treadmills that begin rotating or moving when the animal shows signs of sleeping.  Another procedure involves two adjacent platforms that move above and below water in an alternating fashion.  The animal must continuously move from one platform to the other to stay out of the water.  Another procedure is to have a sweeping bar above the floor of the cage that continuously moves back and forth providing  tactile stimulation to keep the animal awake.  Another process is referred to as “gentle handling” where an experimenter keeps the animal awake by handling it when it tries to go to sleep.  Gently tapping or shaking the cage as well as mild noises have also been used.  Another approach was to introduce novel objects into the cage when the animal shows signs of sleepiness.  Many of these studies find adverse effects in sleep-deprived animals on physiology and behavior.

Figure 3: The inverted flower pot method for preventing REM sleep.

In addition to the disk-over-water method for selectively suppressing REM sleep, the inverted flower pot method has also been used for this purpose with cats and rodents.  As seen in figure 3, the mouse is perched on a very small inverted flower pot in a pool of water.  The animals is able to stay out of the water while awake and also during NREM sleep.  However, when entering REM sleep and losing muscle tone, the animal falls in the water which wakes it up.  The animal climbs back on the flower pot and the process repeats.  This obviously stressful method permits some NREM sleep, but eliminates REM sleep.

Many of these sleep-deprivation studies of animals find dysfunctions overlapping those described earlier for humans. However, Wisden, and Franks (2020) suggest that all of these methods of keeping animals awake are likely stressful to some degree.  In some experiments this conclusion is supported by an increase in blood levels of the stress hormone, corticosterone, however, in others no rise is observed.  However, Wisden and Franks (2020) point out that measuring corticosterone may not always be a good measure of stress.  If the measurement occurs at the end of the study, as was the case in many studies, initial high levels may have returned to baseline.  Corticosterone levels can also be influenced by time of day as well as the conditions under which the corticosterone is taken.

Some scientists have a name for keeping humans chronically awake against their will.  It’s called torture!  For future research, Nollet, Wisden and Franks (2020) suggest that animal research would be more relevant to human research if the animal determines whether it stays awake rather than having wakefulness imposed by an external stressful manipulation.

Given that the parts of the brain controlling sleep have now been extensively mapped, Nollet et al. (2020) suggest it may be possible to get an animals to “choose” to stay awake by manipulating their wake-promoting or sleep-promoting brain circuitry.  Nollet et al (2020) suggest this might be accomplished by either optogenetics or chemogenetics, two relatively new scientific procedures.  Optogenetics uses light-sensitive channels and pumps in the neuron membrane whose genes are virally introduced into neurons.  The neurons’ electrical activity can then be manipulated by a light-emitting probe surgically implanted in the appropriate brain location.  While chemogenetics similarly uses genetically engineered receptors, it uses drugs specific for those receptors, to affect the activity of specific neurons.  These procedures would presumably reduce the stress of keeping the animals awake compared to traditional procedures.  However, Nollet et al (2020) point out that both of these methods are expensive and present both technical and interpretational challenges.

Case Histories of Human Sleep Deprivation.

As mentioned earlier, there are people who, on their own, have stayed awake much longer than would be allowed in a scientific experiment.  Some interesting examples are individuals trying to break the world record for staying awake.  One well-known case is that of Peter Tripp, a New York City Disc Jockey, who, in 1959, stayed awake for 8.8 days as part of publicity stunt to raise money for the March of Dimes.  He remained in a glass booth in Times Square the full time, periodically playing records and bantering to his radio audience.  In 1964, Tripp’s record was surpassed by an 18-year-old Randy Gardner, as part of a high-school science project.  Gardner’s attempt was observed by both a Navy physician and a well-known sleep researcher.  Gardner managed to stay awake for 11.0 days.

After Gardner set his record, the Guinness Book of World Records discontinued awarding world records for staying awake.  They were no doubt influenced by the increasing awareness of the health risks and perhaps by liability considerations.  So…Gardner remains the “official” world record holder.  However, other individuals have since “unofficially” broken Gardner’s record.   Maureen Weston, in 1977,  stayed awake for 18.7 days as part of a rocking chair marathon in England, and Tony Wright, an Australian, stayed awake for 18.9 days in 2007.

So what happened to these people during their attempts?  Over the first couple of days, they became very sleepy and had some perceptual, motor, and cognitive issues but remained reasonably functional.  However, each had to find ways to stay awake.  Tripp had coworkers and a physician to engage and prod him if he started to doze off and over the last 3 days took stimulant drugs to help stay awake.  Gardner played basketball during the day and pinball at night.  Gardner used no stimulant drugs or coffee, although he did drink soda.  Weston rocked in her rocking chair, and Wright thought he was helped by his complex diet of raw foods.

However, after a few days, all began showing more obvious impairments that worsened as deprivation progressed.  The impairments included mood swings, difficulty communicating, memory problems, concentration lapses, blurred vision, difficulties in motor coordination, paranoia, and hallucinations.  Among the worst affected was Peter Tripp.  By the 4th day he was hallucinating about spiders crawling in his shoes, spider webs in his booth, and mice crawling around his feet.  Tripp also began experiencing paranoid delusions that his coworkers and physician were trying to sabotage his effort and by the end of his attempt appeared to suffer a nervous breakdown.  However his 3-day use of stimulant drugs could also have contributed to his schizophrenia-like symptoms.

So what conclusions can we draw?  In all cases, deprivation was associated with psychological, sensory, and motor deficits.  At the same time, it’s also clear that some level of functioning remained.   In fact, on his last night, Gardner was able to beat Dr. Dement, the sleep researcher who studied him, at 100 straight games of pinball, and then the following day gave a press conference in which he appeared remarkably cogent.  (However beating Dement at pinball may say more about Dement’s pinball skills than Gardner’s motor coordination.) When finally able to sleep, all individuals slept more than normal for a night or two, but did not need to make up all their lost sleep before returning to normal sleeping patterns and functioning.

Whether these attempts had lasting consequences isn’t clear.  By some accounts, Tripp was never the same after his experience.  He continued to suffer occasional “psychological” issues, lost his NY City job after being convicted of accepting graft, divorced his wife, and bounced around in various disk jockey jobs in California and Ohio.  Gardner did develop insomnia later in life but whether that was related to his attempt is unclear.   It is possible that some individuals, predisposed to certain problems, might be more affected by extended sleep deprivation than others.

It should be noted that all of these individuals almost certainly experienced undetected microsleeps (most of these attempts occurred before knowledge of microsleeps was widely known).  Microsleeps are more common in humans than in other animals.  Microsleeps have also been suggested to have protected these individuals from the more extreme health outcomes seen in animal research.

Correlational Studies of Chronic Sleep Deprivation in Humans.

Liew and Aung (2020) reviewed 135 publications studying the relationship of sleep deprivation/disruption to the occurrence of various types of health problems.  Many factors contributed, including shift work, stress, parental responsibilities, drug and electronic device use, aging,  insomnia, restless leg syndrome, and sleep apnea.  Regardless of cause, sleep deprivation/disruption was associated with an increased risk for dysfunctions in virtually every organ system of the body.  Sleep deprivation was particularly problematic for children and adolescents still in the process of developing.

Medic et al (2017) reviewed 97 published papers examining both short-term and long-term consequences of sleep disruption.  The consequences included enhanced stress responses,  circadian rhythm disruptions, insulin sensitivity disruptions, enhanced oxygen uptake, enhanced activation of the immune system, and decreased melatonin secretion.   Some of the initial physiological responses might be seen as adaptive attempts to cope with the sleep deprivation. However, as with many things in life, while a little is good, a lot is not better!

And of course, the worst outcome of bad health is premature death.  Cappuccio et al. (2010) performed a meta-analysis of 16 longitudinal studies of the relationship between average sleep duration and longevity.  These studies lasted between 4 and 25 years.  Average sleep duration was self-reported and deaths verified by death certificate.  For the purposes of the meta-analysis, the subjects were divided into 3 sleep-duration categories: normal sleepers (typically 7-8 ½  hours of sleep per night), short-sleepers (typically less than 7 hours/night, but often less than 5 hours/night), and long-sleepers (typically more than 9 hours of sleep per night).   Out of the 1,389,999 male and female subjects in these studies, 112,566 deaths occurred.

Cappuccio et al (2010) found a highly significant U-shaped relationship between sleep duration and likelihood of dying.   Short-sleepers were 12% more likely to have died than normal sleepers, while long-sleepers were 30% more likely.  The pattern was similar in males and females and the effects more obvious in studies utilizing older subjects.   These effects were also greater in Asian populations (particularly in Japan) although this was attributed to older subjects in these studies.

While this meta-analysis demonstrated a clear relationship between average sleep duration and longevity, this research, as well as research relating sleep duration to various health impairments, cannot disentangle cause and effect.  Do abnormal sleep durations impair health which leads to decreases in longevity?  Or does bad health affect sleep duration as well as the likelihood of dying?  Clearly cause and effect can operate in both directions, however this type of research does not effectively address this issue.

CONCLUDING REMARKS.

While there are a lot of unanswered questions, all the different types of sleep-deprivation evidence taken together convincingly support the importance of sleep for brain (and body) functioning.  What isn’t so clear is what is happening inside the sleeping brain that provides these benefits.  The next post presents a variety of (mostly) speculative ideas on how sleep provides benefits to brain functioning.

Meanwhile, I think I’ll go take a nap!

REFERENCES.

Alhola, P., & Polo-Kantola, P. (2007). Sleep deprivation: Impact on cognitive performance. Neuropsychiatric Disease and Treatment, 3(5), 553-567.

Bentivoglio, M., & Grassi-Zucconi, G. (1997). The pioneering experimental studies on sleep deprivation. Sleep, 20(7), 570-576. doi:10.1093/sleep/20.7.570

Cappuccio, F. P., D’Elia, L., Strazzullo, P., & Miller, M. A. (2010). Sleep duration and all-cause mortality: A systematic review and meta-analysis of prospective studies. Sleep, 33(5), 585-592. doi:10.1093/sleep/33.5.585

Liew, S. C. & Aung, T. (2021). Sleep deprivation and its association with diseases – a review. Sleep, 77, 192-204.

Medic, G., Wille, M., & Hemels, M. E. (2017). Short- and long-term health consequences of sleep disruption. Nature and Science of Sleep, 9, 151-161. doi:10.2147/NSS.S134864

Nollet, M., Wisden, W., & Franks, N. P. (2020). Sleep deprivation and stress: A reciprocal relationship. Interface Focus, 10(3), 20190092. doi:10.1098/rsfs.2019.0092

Rechtschaffen, A., & Bergmann, B. M. (2002). Sleep deprivation in the rat: An update of the 1989 paper. Sleep, 25(1), 18-24. doi:10.1093/sleep/25.1.18

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