Sleep in Cognition

Sleep needs no introduction. Every person on earth has had the experience of being asleep, with most people spending up to a third of their lives in this state. However, for the purposes of clarity, let's introduce some definitions.

Sleep is a temporary state of decreased consciousness characterized by reduced wakefulness, inhibition of most incoming sensory information, and lowered muscle activity. Sleep allows the body to regenerate energy and restore tissues used during the day. On a cognitive level, sleep promotes memory formation by consolidating recently learned information.

The daily cycle of alternating between periods of sleep and wakefulness is known as the circadian rhythm. This cycle is regulated by the hormone melatonin, which is secreted at night by the pineal gland in response to low light in the environment. Melatonin decreases wakefulness and promotes sleep.

Secretion of melatonin stops in the morning, at which time the hormone cortisol is at its peak. This alternation between melatonin and cortisol correlates with the subjective feelings of being awake or sleepy throughout a 24-hour period. You can remember the function of both of these hormones by thinking that melatonin makes you want to turn in for the night, while cortisol is released during the daytime in response to solar rays.

Sleep itself is a dynamic process that ebbs and flows throughout the night, even if we are not conscious of this. Sleep generally occurs in sleep cycles that last 90 minutes on average, with most people having 4-6 sleep cycles per night. Sleep cycles involve a regular progression through various stages of sleep as seen in this figure, with hours of sleep on the X-axis and stages of sleep on the Y-axis.

Each stage of sleep is characterized not only by changes in consciousness and behavior, but also by a specific pattern of electrical activity in the brain, which can be seen using an electroencephalogram, or EEG. A sleep cycle proceeds in a regular order from lighter stages of sleep, stages 1 and 2, down towards deeper phases of sleep, stages 3 and 4, which are associated with slower and less frequent activity on EEG. The findings seen in each stage of the sleep cycle, as well as the order they occur in, can be memorized using the mnemonic BAT-STRENK-RED-BLEND.

First, B is for beta waves. The beginning of the sleep cycle is when someone is awake, with beta waves being the pattern of electrical brain activity that occurs during waking consciousness. Next, A is for alpha waves.

On average, people take 15 minutes to fall asleep from the time they go to bed. Between wakefulness and sleep is an in-between state where one feels drowsy but remains conscious. This state is characterized by alpha waves on EEG, which reflect slowed brain activity compared to full wakefulness.

Next, T is for theta waves. Theta waves mark the time when someone crosses over from wakefulness into stage 1 sleep. Stage 1 sleep is also known as light sleep, as someone is just barely asleep and is easily aroused by various stimuli, like the sound of the television in the other room.

Muscle tone is generally reduced, although sudden muscle twitches known as hypnic jerks can occur. Next, S is for sleep spindles and K-complexes. Stage 2 sleep is characterized by a full absence of consciousness and a further decrease in muscle tone.

On EEG, this appears in the form of specific patterns of electrical activity known as sleep spindles and K-complexes. Next, D is for delta waves. The presence of low frequency delta waves characterizes deep sleep, which you can remember by focusing on the first two letters of both delta and deep.

Deep sleep is the most restorative phase of sleep, both physically and mentally. In this state, someone becomes unaware of all but the most intrusive external stimuli. For example, outside traffic noise or the sound of a television are typically blocked out, although louder noises, like an alarm clock going off, may break someone out of this stage of sleep.

Next, R is for rapid eye movement. Rapid eye movement, or REM sleep, which is named for the someone's eyes are noted to move rapidly during this time even though the eyelids remain closed, is a paradoxical stage of sleep in which the brain's level of activity is increased to the point where it resembles an awake state on EEG, all despite still being asleep. This results in two distinct patterns that you should memorize, as they will come up a few times when talking about sleep disorders later in this lecture.

Luckily, both of these patterns start with the letters REM. First, REM sleep is when you are most likely to remember your dreams, as this is when the most dramatic dreaming occurs, with some studies estimating that around 80% of all dreams occur during this stage. Despite all this mental activity, someone in a state of REM sleep is likely to physically remain still, as REM sleep is associated with muscle paralysis throughout the body, with only the muscles of breathing and eye movement remaining active.

This widespread muscle paralysis is a good thing, as without it we would likely act out our dreams at night and not get very much rest. Finally, B is for back again. Following REM sleep, the brain moves backwards through the previous stages of sleep and then begins another cycle.

This cycle between REM and non-REM sleep repeats several times per night. After enough time, the person spontaneously wakes up. Someone waking up from a lighter stage of sleep often feels more well-rested than if they had woken from a up directly from deeper sleep.

At this point, the amount of melatonin secretion is minimal, while levels of cortisol are near their highest levels, creating a sensation of alertness and wakefulness to prepare for the day ahead. With that basic understanding of sleep physiology covered, let's turn our attention to sleep disorders. By far the most common form of sleep disorder is insomnia, which is defined as any form of difficulty sleeping, including trouble falling asleep, awakening during the night, or waking up earlier than desired.

Insomnia is not inherently pathological, and occasional nights of bad sleep are completely normal. However, if the inability to sleep continues for too long or becomes severe, it can be the source of disability, distress, and dysfunction. Symptomatically, people with chronic insomnia often struggle with fatigue, poor mood, irritability, and inattention throughout the day.

Patients with chronic insomnia often report feeling some level of distress or worry about their lack of sleep as well. Insomnia is common, with around 30% of the population reporting problems with sleep on at least an occasional basis. For this reason, insomnia should not be considered a disorder until it becomes frequent and severe.

Most cases are secondary, with insomnia being caused by upstream factors like lifestyle, drugs, or other disorders. Once these have been excluded, the prevalence of primary insomnia falls to around 5% of the general population. Age and gender are the largest risk factors for insomnia, with older adults and women both being at higher risk compared to the rest of the population.

The presence of a comorbid psychiatric disorder is also a major risk factor, with studies showing that around 40% of all people with recurrent insomnia meet criteria for at least one mental disorder, compared to only 15% of people without sleep complaints. Of these, depression is the most common, although anxiety is a close second. As a general rule, insomnia tends to be persistent, although it may come and go in an episodic fashion for some patients.

Chronic insomnia is associated with worse outcomes in nearly all areas of one's life, including physical health, mental well-being, pain perception, and levels of social support. Physical and cognitive performance decreases as well, with patients who miss even one night of sleep driving just as badly, if not worse, than someone who is under the influence of alcohol. In fact, people who are chronically sleep-deprived have a rate of accidents that's up to 5 times higher than the average.

All of these together predict a greatly increased risk of mortality, with severe insomnia, or sleeping less than 4 hours a night, being associated with a 15% higher mortality rate. Treatment of insomnia involves therapy, medications, or both. The first-line treatment should be a type of CBT known as Cognitive Behavioral Therapy for Insomnia, or CBTI.

CBTI involves practicing good sleep hygiene, combined with addressing and correcting any dysfunctional beliefs that may be contributing to sleep-related anxiety, such as countering the incredibly common, though completely inaccurate, belief that if you don't get enough sleep on any particular night, then you're going to have a terrible time the next day. CBTI has been associated with major reductions in the subjective sleep-related distress that a patient experiences, as well as lesser, though still significant, objective improvements in the amount and quality of sleep that they get. In addition, the beneficial effects of CBTI tend to persist even after treatment has ended.

Medications used to treat insomnia are known as hypnotics and consist of a wide variety of drugs with different mechanisms of action, including antihistamines like diphenhydramine or Benadryl, benzodiazepines like lorazepam or Ativan, and Z-drugs like zolpidem or Ambien. While the efficacy of these drugs varies depending on the class, as a whole, their effects tend to be limited to the time in which they're taken, and people often develop tolerance to their sedative effects after only a few nights of regular use. Furthermore, hypnotics can cause daytime sedation and poor balance, leading to an increased risk of falls, especially in the elderly.

For this reason, hypnotic drugs should generally be recommended only after other interventions such as CBTI have been tried, and even then they should be prescribed for as short a period of time as possible. In addition to primary insomnia, there are a few other disorders that can impact the amount or quality of sleep that a person gets. Let's go over a few of the highest yield disorders to know as we close out this lecture.

First, obstructive sleep apnea, or OSA, is a condition in which people suffer from brief but recurrent episodes of apnea, or pauses in breathing, throughout the night. This occurs as a result of anatomical blockage of the airways due to both the muscle relaxation that occurs during sleep, as well as the recumbent position that most people sleep in. These hypoxic episodes lead to transient micro-awakenings that occur throughout the night and prevent the person from entering into deep sleep, resulting in sleep that is not restorative.

This leads to persistent daytime fatigue and other symptoms such as headaches. While intuitively it would seem like the sleep disruption seen in this disorder would make people (more able to fall asleep at night, studies have shown that as many as half of all people with OSA still struggle with bedtime insomnia. For this reason, make sure to ask about OSA in anyone presenting with chronic fatigue, as patients are not always aware that they are waking up frequently at night.

You can use the mnemonic STOP BANG to remember the specific factors that are predictive of OSA, including snoring loudly, feeling tired all the time, apneic episodes that have been directly observed by someone else, high blood pressure, high body mass index, older age, a large neck circumference, and male gender. OSA is a major threat to health as untreated cases are associated with a higher risk of heart attack and stroke. Treatment for OSA involves using a Continuous Positive Airway Pressure or CPAP machine that provides a steady stream of air to keep the airway from getting compressed.

Next, Restless Leg Syndrome or RLS is a condition in which a person experiences recurrent feelings of restlessness while trying to sleep. You can remember the key clinical features using the mnemonic URGE, which will remind you that patients feel an urge to move their legs, that this urge not only worsens with rest but also gets better with activity, like moving one's legs, and that the feeling is more pronounced in the evening when trying to sleep. RLS can impair both the amount and quality of sleep, leading to symptoms of sleep deprivation.

Around half of all cases of RLS are idiopathic, with genetics playing a large role. However, it can also occur as a result of other medical or psychiatric conditions. The most common culprit is iron deficiency, which is seen in about 20% of all cases.

For idiopathic cases, no curative treatments are available. Instead, a variety of symptomatic treatments can help to improve sleep duration and quality of life. You can remember these using the mnemonic LAID, which stands for Lifestyle Changes Including Sleep Hygiene, Caffeine Avoidance and Smoking Cessation, Anticonvulsants and specifically gabapentin or pregabalin, which are a good first-line option for medication treatment, iron supplementation in cases where iron deficiency is involved, and finally dopamine agonists like pramipexole or ropinarol, although these drugs are used less often these days as, despite being  effective in the short term, they often make restlessness worse in the long term and come with some pretty severe side effects.

By considering these treatment strategies, you can make sure that the patient's RLS has been laid to restless. Next, people who are not able to consistently follow a set daily schedule, such as those who work night shifts or travel across time zones, are at risk for circadian rhythm disorders, often just called jet lag. These disorders are characterized by excessive sleepiness during the daytime, when they should be awake, and involuntary wakefulness at night, when they should be asleep.

Providing education on sleep hygiene, such as avoidance of naps and caffeine prior to sleep, can be an initial first step. For those with excessive difficulty falling asleep at night, melatonin supplements can be incredibly helpful. For those with difficulty staying awake during the day, exposure to bright lights can be effective, as can the medication modafinil, which helps to promote wakefulness.

Next, sleepwalking, also called somnambulism, is when an individual performs activities as if they are awake, despite being in a state of deep sleep. This most commonly involves walking around, although other activities such as going to the bathroom, cooking, and even driving have been reported. Sleepwalking is a type of parasomnia, a category of sleep disorders characterized by abnormal movements or behaviors during sleep.

Parasomnias like sleepwalking occur during slow-wave sleep, when muscles are not paralyzed like they are during REM sleep. Most cases of sleepwalking are idiopathic, with no clear cause ever being found. However, in some cases they may be related to use of Z-drugs like zolpidem.

The next three disorders we'll talk about all involve unpleasant or even terrifying experiences that occur around sleep. First is nightmare disorder, which, naturally, occurs during REM sleep, when people are most likely to REMember their dreams. Most people have nightmares from time to time, but a minority of people are afflicted by nightmares that are frequent or severe enough to qualify as a disorder.

People with nightmare disorder are more likely to have a history of trauma. If treatment is desired, stress reduction techniques such as mindfulness can help, as can the medication prazosin, which has been shown to reduce the frequency and severity of nightmares. Next, sleep terrors, also called night terrors, differ from nightmares in that they occur during non-REM sleep, and the patient is usually unable to remember what they were dreaming about.

However, upon awakening they are clearly distressed, often crying out or sitting upright with eyes wide open. Physiologic signs can resemble a panic attack, with tachycardia and hyperventilation being common. Sleep terrors most often occur during childhood, and the majority of cases do not persist into adulthood, with less than 1% of adults experiencing sleep terrors on a regular basis.

For this reason, reassurance is typically sufficient treatment for children who suffer from sleep terrors, as well as their parents. Capping off the trio of conditions involving terrifying experiences while asleep is sleep paralysis. Sleep paralysis occurs when someone wakes up from REM sleep and gains consciousness of the world, but remains unable to move.

This sensation is often accompanied by a feeling of fear or panic. In addition, many people report a distinct sensation of being watched and can even hallucinate a malevolent figure in the room. In this way, we see what happens when the two components of REM sleep, remembering dreams and remaining still, persist even after the patient has woken up.

They are still paralyzed and in a hallucinatory dream state, but they are now conscious of it, resulting in a terrifying experience. Episodes of sleep paralysis can be highly disturbing, especially if they are so frequent or severe that the patient develops anxiety about going to bed. Up to half of all adults have experienced at least one episode of sleep paralysis, although less than 5% experience them on a regular basis.

Education on the nature of sleep paralysis and teaching of relaxation techniques can often be treatment enough, although in more severe cases CBT or serotonin boosting medications like SSRIs can be used. The last two disorders we'll talk about also involve abnormalities of the REM sleep state. First, REM sleep behavior disorder is characterized by abnormal movements during REM sleep, as the remaining still part of REM sleep has been lost while the remembering dreams part remains.

This lack of muscle paralysis during REM sleep leads to the patient acting out their dreams, which can be very disruptive to others sharing the bed, and patients with REM sleep behavior disorder can sometimes even unintentionally injure themselves or their partners if they are experiencing a particularly violent dream. REM sleep behavior disorder rarely occurs on its own, with more than 90% of patients going on to have a neurologic disorder, with Parkinson's disease and dementia with Lewy bodies being common. Melatonin is a first-line option for treatment, as it is both effective and well tolerated.

Taking steps to make the sleep environment safer, such as putting another mattress on the ground in case the patient 10rolls off the bed, can also help to prevent against injuries. Finally, narcolepsy is a neurological disorder characterized by both excessive daytime sleepiness and abnormalities of REM sleep that result in a set of highly characteristic signs and symptoms. The mnemonic CHAP will help you remember these.

First, C is for cataplexy. Cataplexy refers to sudden episodes of muscle paralysis during wakefulness. This can span the range from more subtle signs, such as slight weakness in one's limbs, all the way up to more dramatic events, such as collapsing on the ground due to a complete loss in muscle tone.

Cataplexy is often triggered by strong emotional states, but it can occur out of the blue as well. Cataplexy is caused by sudden daytime activation of the same remaining still muscle paralysis seen in REM sleep and is one manifestation of the REM sleep abnormalities seen in this disorder. Cataplexy is unique to narcolepsy, making it a very specific sign of this disorder.

Next, H is for hypnagogic and hypnopompic hallucinations. The term hypnagogic refers to the transition from wakefulness to sleep, while hypnopompic refers to the transition from sleep to wakefulness. You can remember this difference between hypnagogic and hypnopompic hallucinations by thinking that hypnagogic hallucinations occur when you're groggy at night, while hypnopompic hallucinations happen when you need to pump yourself up in the morning.

People with narcolepsy are known to experience vivid hallucinations during both of these sleep transitions. This imagery can range from random lights or speckles all the way to fully formed images of people and places. In this way, hypnagogic and hypnopompic hallucinations represent yet another way in which narcolepsy involves abnormalities of the REM sleep state, as patients experience the remembering dreams part even though they are still partially awake.

Next, A is for sleep attacks. One of the core features of narcolepsy is excessive daytime sleepiness, which is experienced even when the patient gets enough sleep at night. For some patients, the drive towards sleep becomes so strong that they have episodes of suddenly falling asleep without intending to, sometimes even while walking, driving, or doing other activities.

These sleep attacks typically last only a few seconds or minutes, but due to their unpredictable nature, they can be incredibly distressing and impairing. While sleep attacks are perhaps the most dramatic and well-known sign of narcolepsy, not all people with this disorder experience them. Finally, P is for sleep paralysis.

Episodes of sleep paralysis, as described earlier in this lecture, are common in narcolepsy and, like the other signs of this disorder, represent a manifestation of the tendency these patients have towards experiencing alterations of REM sleep, with remembering dreams and remaining still happening even after the patient wakes up. While diagnosing narcolepsy is easy when someone has all four of these clinical features, not everyone with narcolepsy does. In cases where the diagnosis is less clear, sleep studies can help to detect the specific abnormalities, such as rapid transitions between wakefulness and REM sleep, that characterize narcolepsy.

Narcolepsy is a rare diagnosis, affecting less than 0.1% of the population, although it may be underdiagnosed, especially in people who do not have all four of their characteristic signs and symptoms. It tends to have its onset during adolescence and early adulthood, with men and women being affected equally. Narcolepsy is a lifelong condition that can result in ongoing distress and disability if left untreated.

No definitive cure exists, so treatment is focused instead on managing the symptoms to enable the patient to live a decent life. Sodium oxibate, better known by its street name gamma-hydroxybutyric acid, or GHB, is effective at reducing the severity of multiple symptoms of narcolepsy, including excessive daytime sleepiness, episodes of cataplexy, and altered sleep architecture. Conversely, the wakefulness-enhancing drug modafinil is effective at reducing daytime sleepiness and sleep attacks, but does not significantly affect episodes of cataplexy.

Careful maintenance of sleep hygiene and avoidance of sleep-impairing substances like caffeine and alcohol are crucial as well. Behavioral and lifestyle changes such as scheduling naps and exercise sessions can also be beneficial. And with that, we have completed our introduction to the world of both sleep and its associated disorders.

Sleep is a vital part of life that is essential not only for living, but for living well. Because of the close relationship of sleep to both physical and mental health, consider making an assessment of the patient's sleep patterns a core part of every medical evaluation, as there is often a lot that can be done to help the patient improve not only the quality of their sleep, but also the quality of their life as well.