Sleep Deprivation

Figure 1. Effects of Sleep Deprivation
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Some of the physical and mental manifestations of sleep deprivation[3].

Sleep deprivation (SD) can be defined as either complete lack of sleep, or just not getting enough of it, as is very common in contemporary Western lifestyles[1]. Sleep plays a crucial and complex role in the brain and body, and is necessary for many different cognitive and homeostatic functions. Sleep deprivation, especially when chronic, can therefore have multiple detrimental effects on the brain and body. General cognitive function and cellular processes are impaired in areas such as attention, emotion, learning and memory[2]. Other manifestations of sleep deprivation include reduced coordination of movement, fatigue, irritability, micro-episodes of sleep, and may involve hallucinations or other perceptual disorders[1]. This section of the neurowiki on sleep will be focusing on cognitive impairment caused by SD, its effects on metabolite clearance, and will conclude with a suggested optimal sleep schedule for learning.

1. Animal Models of Sleep Deprivation

Animal models are an essential tool in the study of sleep deprivation and its effects on the mind. This is especially due to the fact that human studies can only be conducted for a short amount of time to prevent long-term health effects, and the findings that animal models all die after about two weeks of total sleep deprivation. There are a number of animal models that are used to study the consequences and potential treatments of sleep deprivation; however each model has its own strengths and weaknesses as it is difficult to control for confounds that may have other effects on the animal. It is also important to note that, while animal models are useful, one must apply caution when generalizing the results to humans. Papers by Alkadhi et al.[2] and Colavito et al.[4]thoroughly describe these models, which I will recapitulate here.

Figure 2. Rotating Disc Over Water Method
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Both the control and test mouse are placed on a disc
suspended above water. When the EEG shows that the test mouse
has fallen asleep, the experimenter will rotate the disc so that it has
to walk to prevent falling into the water. The control mouse is yoked
so that there is no danger of falling into the water[5].

1.1. Forced Locomotion

Some of the earliest models use forced locomotion as a way to prevent mice from sleeping; two examples of this are the rotating disc over water model and the treadmill model. The rotating disc over water model (see Figure 2) is used to prevent either specific phases or all phases of sleep by gently rotating a disc when EEG patterns indicate that the test animal has fallen asleep, or has entered an unwanted sleep phase. If the animal doesn’t wake up and start walking, it will fall into the water. The control animal in this experiment also is placed on a disc but is yoked so that it has no danger of falling into the water. The treadmill model is another effective tool to deprive the test animal of all phases of sleep. In a similar manner to the rotating disc model, the EEG patterns of the mouse are recorded via electrodes placed into its brain. The treadmill is programmed to move for 3 seconds and stop for 12 seconds to achieve sleep deprivation by forcing the mice to be in motion. Control mice instead are put on a treadmill that moves for 15 minutes and stops for 60 minutes, allowing more time to rest. The main weakness of these models is the physical stress and fatigue that may have effects on the mice beyond simple sleep deprivation[2][4].

1.2. Gentle Handling Model

This paradigm is used to selectively abolish a specific unwanted sleep phase by introducing a stimulus when EEG patterns indicate that the test animal has entered that phase. These stimuli can be tactile, oral, or visual, and the experimenter’s constant presence is required to introduce them at the appropriate time. For this reason, this model is often only used for short periods of sleep deprivation. Two main weaknesses of this model is that the animal may adapt to the stimulus and will no longer be awakened by it, and that there may be unintended confounding results due to the enrichment of the environment by providing new stimuli[2][4].

1.3. Head-Lifting Model

Figure 3. Multiple Platforms Technique
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The mouse is placed on a small platform that rises two inches above
the water level in the tank. Loss of muscle tone when entering REM sleep
will cause the animal to fall into the water and awaken. This is used to
effectively deprive it of REM sleep[6].

This model involves gently lifting the test animal’s head through a system of pulleys and levers by the experimenter who sits in a separate room, measuring the EEG readouts of the animal. It is used to selectively deprive the test animal of REM sleep, and was developed to minimize the extra stresses and physical exertion seen in techniques such as the treadmill model. In addition, the experimenter is not required to be in the same room as the test animal, unlike in the other models[2][4].

1.4. Enlarged Environment

Enlarging the environment of mice and rats causes sleep deprivation by exploiting their instinctual nature to explore new environments. This technique can only be used for short-term total sleep deprivation due to the physical limits of the space that can be provided. This model is unique in that it does not seem to cause any undue stress to the test animal; however there may be confounding effects due to the enriched environment, and can affect results on cognitive and behavioural tasks[2][4].

1.5. Multiple Platforms Technique

As can be seen in Figure 3, this method involves a small platform that rises two inches above the water level in a tank. The test animal is placed on this platform, and is prevented from entering REM sleep because the loss of muscle tone that occurs with REM sleep causes it to fall in the water and awaken. In contrast, a control animal is placed on a platform with enough room to sleep comfortably and not fall into the water. This technique has been improved to include multiple platforms in a single water tank to control for isolation and psychosocial stress seen in the original set up[2][4].

2. Effect on Cognition

What If You Stopped Sleeping?
This short video describes some of the physical and mental consequences of ceasing to sleep, and how the severity
of its effect on your body worsens the longer you go without sleep. The narrator succinctly summarizes several current
research findings on sleep deprivation, including its effect on cognition,metabolism, and your immune system[18].

Sleep Deprivation (SD) has widespread detrimental consequences on cognition, seen in both animal subjects and human participants. In a recent study by Molfese et al., they found that a mere one hour period of sleep deprivation negatively affected the amplitude of children’s ERP responses on tasks such as attention, speech perception, and executive function[7]. Similar results have been found in adult subjects; in studies testing both short- and long-term sleep deprivation, subjects show impairment in both simple and complex tasks, including reaction time, attention, working memory, logical reasoning, and decision making[8],[9].

To compensate for the inadequate task performance of certain brain areas during lack of sleep, it is possible that the brain may recruit other areas to increase motivation and function. For example, PET studies have shown that the prefrontal cortex, frontal cortex, and thalamus all show decreased levels of glucose usage after sleep deprivation, while areas such as the right parietal lobe show increased activity during tasks that would normally activate the temporal lobe such as verbal reasoning or mathematic calculations[10]. This shows that in the short-term, the brain is able to compensate for the detrimental effects of sleep deprivation, but does not operate at peak efficiency.

3. Effect on Learning and Memory

Sleep deprivation negatively affects a wide variety of pathways and molecules involved in learning and memory. Neurogenesis in the hippocampus, LTP, NMDA receptor trafficking, and CREB activity are just some of the victims of lack of sleep[2]. For a more global picture of what sleep deprivation can do to learning and memory, Alzoubi et al. used the modified multiple platform method to induce sleep deprivation in rats and found that these rats performed significantly worse on Radial Arm Water Maze tasks compared to controls when being tested for both long and short term memory[11]. Similar studies have consistently found impaired learning and memory in rodents when tested in Morris Water Maze and Novel Arm Recognition tasks[2],[11],[12].

Prince et al. found the precise time window when sleep deprivation has the most effect on hippocampal LTP and memory consolidation. The authors trained mice in an object placement task that is known to involve hippocampal-dependent spatial learning. They show that only 3 hours of sleep deprivation after the training impaired both LTP and long-term memory[13]. Sleep after learning is an important step in consolidating what we have learnt. This is show in human subjects by Beijamini et al., where after being presented with a logical reasoning problem, participants who were able to sleep for 90 minutes were twice as likely to solve the problem compared to the control group, who had 90 minutes of quiet wakefulness[14]. Together, these results show that sleep is an important part of learning and memory, especially after a new task or training has been presented, in both animals and humans.

4. Effect on Metabolite Clearance

Unlike the rest of the body, the brain does not have a lymphatic system and instead rids itself of toxins and wastes such as β-amyloid (Aβ) protein through exchange between the cerebrospinal fluid (CSF) and the interstitial fluid (ISF) at the arteries and veins. Xie et al. infused fluorescent CSF tracers into the brains of asleep and awake mice. Using electrocorticography (ECoG) and electromyography (EMG), the authors showed that inflow of tracer into the brain was significantly reduced in awake mice compared to sleeping ones by almost 95%. The same difference was seen between awake and anesthetized mice. Xie et al. found that this difference in influx of CSF was due to increased interstitial volume during sleep, which allows easier diffusion of neurotransmitters, toxins, and wastes, including two-fold more efficient clearance of Aβ[15]. These results show that sleep may play a central role in clearing and degrading metabolites, which would otherwise accumulate and have potentially detrimental effects.

5. Optimal Sleep Schedule for Learning

As a university student, I know that it is sometimes difficult to get enough sleep every night. A sleep schedule that requires less sleep and more awake hours would be a gift in our busy, deadline-filled, time-crunched society. Unfortunately, there is no quick fix, no magic cure for the basic need to sleep. No sleep schedule can successfully replace the normal monophasic sleep pattern for long periods of time. Getting the right amount of sleep each night is necessary for your brain and body. The optimal amount of sleep is 7.5 to 9 hours per night[16]. While the monophasic sleep pattern is the optimal way to achieve a good night’s sleep, a Siesta, or biphasic, pattern of sleeping is also a viable option. The Siesta pattern involves a shorter amount of sleep during the night with the addition of a nap in the middle of the day, usually early afternoon. See the Sleep Patterns page for more information on alternative sleep schedules.

5.1 How to Help Your Brain When You Are Sleep Deprived

To augment your sleeping schedule, it is crucial to get enough exercise. This increases BDNF levels in the brain, which promotes neurogenesis, and therefore improves learning and memory. BDNF levels and neurogenesis both fall under sleep deprivation[2], and exercising is a good way to offset the damaging effects of an all-nighter. Please see the Exercise and Neurogenesis page for more information. Another way to save your brain’s capacity for LTP is to drink caffeine. Alhaider et al. have shown that chronic caffeine treatment in mice prevented LTP impairment in the hippocampus due to sleep deprivation[17]. In a pinch, standing upright can surprisingly reduce the effects of sleepiness and rescue your capacity for learning and memory when sleep deprived[2].

Bibliography
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3. Haggstrom, Mikael. (2009 May 29). Effects of Sleep Deprivation. [Image]. Retrieved from http://en.wikipedia.org/wiki/Sleep_deprivation
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11. Alzoubi K. H., Khabour O. F., Salah H. A., & Abu Rashid B. E., The Combined Effect of Sleep Deprivation and Western Diet on Spatial Learning and Memory: Role of BDNF 
and Oxidative Stress. J Mol Neurosci. (2013) 50:124-133.
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18. AsapSCIENCE. (2013, September 22). What If You Stopped Sleeping? Retrieved March 29, 2014, from http://www.youtube.com/watch?v=nNhDkKAvxFk

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