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Day # 151: Why We Sleep: An Overview of Sleep Physiology

Today we will begin a new theme: sleep disorders. We will start by providing an overview of important sleep physiology.

Today's Content Level: All levels (Beginner, Intermediate, Advanced)

Why Do We Sleep? 1, 2

• Why we sleep remains one of nature’s greatest mysteries.

•The average person will spend about 27 years of their lifetime sleeping.

•Sleep is essential for many vital functions and a number of theories have been proposed regarding the purpose and function of sleep.

Somatic theories: energy conservation, physical development, modulation of immune system responses, and physical performance (e.g. securing sufficient performance for survival).
Neural metabolic theories: detoxification and regeneration (brain waste clearance via the glymphatic system) and other metabolic functions.
Cognitive theories: learning, memory consolidation, synaptic plasticity, neurodevelopment, and overall cognitive performance.

Why We Sleep by Mathew Walker

Overview of Sleep Physiology and Sleep Architecture 3, 4

•Sleep is not simply unconsciousness! Sleep is a complex process dependent on multiple brain pathways. There are vital processes our brain goes through during sleep.

•Normal sleep is broken up into a number of different sleep cycles. Each cycle occurs about every 90 minutes with approximately 4-6 of these 90 minute cycles occurring per major sleep episode. These cycles are sometimes called ultradian rhythms which are regulated in a number of brain areas.

•These cycles are defined in terms of brain wave activity, eye movements, and motor activity.

•During each ~90 minute cycle, sleep is further broken down into four stages of sleep: Rapid Eye Movement (REM) sleep and three separate stages of Non-Rapid Eye Movement (NREM) sleep.

•Polysomnography (PSG) studies using electroencephalography (EEG) have revealed a number of differences between these stages of sleep including the length and frequency of electrical wavelengths in the brain. I will include relevant information often tested on psychiatry shelf or board exams for each phase of sleep.

Non-Rapid Eye Movement (NREM)

•70-80% of sleep is spent in NREM.

•↓ HR, BP, RR, body temp, muscle tone

•N1: This stage marks the transition from wakefulness to sleep. It is a light sleep stage and is brief in duration. Eye movements are slow and may include occasional slow eye rolls. Alpha brain waves (8-12 Hz) (associated with wakefulness) are replaced by theta waves (4-7 Hz). Occasional positive occipital sharp transients (POSTS) of sleep can be seen. It is relatively easy to be awakened from this stage. May experience hypnic jerks or sudden muscle contractions.

•N2: This stage occurs after N1 and is longer in duration, making up a significant portion of the sleep cycle. It is more difficult to be woken from sleep compared to N1. Eye movements are minimal. Brain waves are similar to N1, however sleep spindles (short bursts of rapid oscillations) and K-complexes (larger, slower waves) are also present. There is no alpha wave activity. Benzodiazepines increase the total amount of time spent in N2 sleep at the expense of N3 and REM. N2 sleep is important for detoxification/regeneration and preparation for deep sleep.

•N3: Often called “slow wave” sleep or “deep sleep.” This is the deepest stage of NREM sleep and is more difficult to wake someone during this stage. It accounts for a smaller portion of the sleep cycle, typically occurring in the earlier part of the night. Delta waves (0.5-4 Hz) are present which are slow and high amplitude. Parasomnias (e.g. sleep walking, sleep terrors, confusional arousals, sexsomnia, and sleep-related eating disorder) occur during this stage. This stage decreases with old age. N3 sleep is critical for memory consolidation (declarative and procedural memories), information processing, and physical restoration and growth (growth hormone is released in N3).

Rapid Eye Movement (REM)

•20-25% of sleep is spent in REM.

•↑ HR, BP, RR, metabolic rate.

•Typically occurs cyclically every 90 minutes, with the first REM period occurring about 90 minutes after falling asleep.

•REM sleep episodes become progressively longer throughout the night, with each lasting longer than the previous one.

•Rapid eye movements are a hallmark of REM sleep and are often associated with vivid dreaming. Dreaming can occur during other sleep stages, but it is particularly intense and complex during REM sleep.

•Voluntary muscles of the body are paralyzed (except for the extraocular muscles), known as muscle atonia. This prevents dreams from being acted out.

•Brain waves appear very similar to the awake brain. Low-voltage mixed frequency activity with sawtooth waves, theta activity, and slow alpha activity is seen.

•Heart rate and breathing become more irregular.

•REM sleep is important for emotional regulation and creating novel connections between learned information.

Two Important Drivers of Sleep: Homeostatic Drive + Circadian Rhythm 5, 6

•Homeostatic drive and the circadian rhythm work in tandem to control sleep timing and quality.

Homeostatic Drive

•Homeostatic drive = “sleep drive” or “sleep pressure.”

•Sleep pressure steadily builds throughout the day and regulates tiredness and sleep onset. This sleep pressure decreases when we are asleep.

•The nucleoside, adenosine, plays a critical role in this process. Adenosine naturally accumulates in the brain over the course of wakefulness as a byproduct of the breakdown of adenosine triphosphate (ATP), which is the primary energy currency of cells. Excess adenosine binds to receptors (A1, A2A) which inhibits neuronal activity, leading to a reduction in excitatory neurotransmitter release (e.g. dopamine, glutamate). The reduction in excitatory neurotransmission facilitates the transition from wakefulness to sleep. Adenosine levels decline during sleep as a result of various mechanisms, including active transport out of the brain and enzymatic breakdown. This reduction in adenosine levels contributes to the restoration of wakefulness upon waking.

•The role of adenosine in sleep physiology helps us understand the use of caffeine to promote the feeling of wakefulness. Caffeine blocks adenosine receptors, thus counteracting the inhibitory actions of adenosine, temporarily reducing the feeling of sleepiness and promoting wakefulness.

•GABA, as the primary inhibitory neurotransmitter in the brain, also plays an important role as sleep-promoting neurons in the anterior hypothalamus release GABA, which inhibits wake-promoting regions in the hypothalamus and brainstem.

•Excitatory neurochemicals such as acetylcholine, dopamine, norepinephrine, histamine (HA), and the peptide hypocretin rise in the morning and maintain the waking state.

Circadian Rhythm

•Circadian rhythm = roughly 24-hour cycle that is synchronized with the day-night cycle of the Earth.

•Sometimes called the body’s internal biological clock. It is a timing mechanism in the brain that uses light/dark exposure to synchronize the sleep-wake cycle with the external environment.

•Regulated by a central pacemaker located in the hypothalamus, specifically in the suprachiasmatic nucleus (SCN).

•Influences the production of melatonin in the pineal gland. Melatonin is an important hormone that plays a key role in the sleep-wake cycle. Melatonin is typically produced in larger quantities in the evening and during the night which promotes sleepiness. Exposure to light, especially in the morning, activates the SCN which in turn suppresses melatonin production in the pineal gland, contributing to wakefulness.

•The circadian rhythm opposes homeostatic drive while we are awake and, unlike sleep drive, it is not affected by previous sleep.