Review of REM Sleep: Part One – Physiology

by Amalia A. Geller, MD

The reasons we dream and the purpose for Rapid Eye Movement (REM) sleep remain a mystery. We still do not understand why humans need to dream, but we do understand more about the physiology. The purpose of this two-part article is to gain a better understanding of what occurs during REM sleep (part one) and understand the pathological disease states that directly target REM sleep, specifically REM Behavior Disorder (RBD). There are some very interesting hypothetical reasons for the purpose of dreaming which we will touch upon in part two. Part two also will contain several updates on cutting-edge data for diagnosing and managing RBD.

Normal REM Sleep

REM sleep occurs about 90 minutes into the sleep cycle in healthy young adults. The first REM episode is the least intense and may only last 5-10 minutes. After this initial episode, REM sleep begins to alternate with Non-Rapid Eye Movement (NREM) at approximately 90-minute intervals. Individuals usually experience 4-5 REM-NREM cycles during sleep. REM sleep cycles increase and become more intense toward the end of sleep with each REM period lasting 30-60 minutes. N3 sleep (the deepest stage of NREM sleep) becomes progressively less frequent during the night, and our final sleep period is made up of N2 NREM and REM.

REM sleep accounts for 20-25% of sleep time in young adults, while only accounting for 17-20% of sleep in the elderly. While REM sleep in infants and children resembles adults, the dominant frequency is slower, and the voltage is higher in younger infants and children. Dominant R frequency increases with age from 3 Hz activity at 7-8 weeks, to 4-5 Hz activity with bursts of saw tooth waves at 5 months, to 4-6 Hz at 9 months, and to prolonged runs/bursts of notched 5-7 Hz activity by 1-5 years of age. After 5 years of age, REM sleep patterns are similar to adults with the exception of higher amplitude brainwave activity.

REM Physiology

REM sleep consists of both sympathetic and parasympathetic activity. The eyes move rapidly behind closed eye lids, heart rate speeds up, and breathing becomes irregular. Respiratory instability — brief pauses with brief episodes of increased respiratory rate — is often seen in children during REM sleep. In contrast to other stages of sleep, in which brain waves slow down, the brain is highly active during REM sleep. REM sleep is known as the stage most associated with vivid dreaming because of heightened brain activity. Most of the cortical regions of the brain are activated. Areas of the brain that control REM are the pedunculopontine tegmentum, pontine lateral dorsal, tegmental, and lateral dorsal nuclei. Cerebral blood flow is increased during REM sleep and decreased during NREM sleep.

Several neurotransmitters are involved in REM sleep. Acetylcholine (ACh) is the main neurotransmitter during REM sleep produced by the cholinergic neurons in the pedunculopontine tegmental nucleus (PPT) and the lateral-dorsal tegmental nucleus (LDT). ACh is also located in the basal forebrain which projects directly to the cerebral cortex. ACh from the PPT and LDT have an excitatory action on the thalamic relay neurons and inhibit gamma amino butyric acid (GABA) neurons in the thalamus. GABA is located in the ventrolateral preoptic nucleus (VLPO) and other regions throughout the brain. Active during sleep, both GABA and galanin inhibit arousal systems and are inhibited during wakefulness by norepinephrine, 5-HT, ACh, and histamine. The neurotransmitter glycine is responsible for REM muscle atonia.

In addition to the central nervous system activation, there are several important reflexes involved in REM sleep.

• The H reflex is an electrical counterpart of the mono-somatic muscle stretch reflex. During REM sleep, there is a decrease in amplitude of this reflex because motor neurons are hyperpolarized leading to presynaptic inhibition and facilitation of the brain stem neurons. Also, there is facilitation of the lateral hypothalamic and orexinergic neurons.
• The polysynthetic blink reflex is also reduced in amplitude and excitability during NREM but recovered during REM sleep. In fact, the polysynaptic blink reflex is almost the same during REM sleep as it is during wakefulness.
• The flexor reflex is in the lower limbs in humans. This is another synaptic spinal reflex, which has early and late components. It’s mediated by A-delta (δ) and C fibers, which are both types of sensory nerve fibers responsible for transmitting pain signals. During REM sleep, maximum amplitude is seen.

Along with the reflex activity in REM, sympathetic blood flow is decreased to cutaneous and muscular areas of the body but is increased in mesenteric and renal flow. (Note: During all sleep stages, there is decreased GFR, increased renin, increased water reabsorption, and decreased urine production.) Body temperature rises during REM due to an increase in cerebral metabolic activity and cerebral blood flow. However, thermal regulatory mechanisms are essentially inoperative during REM sleep. Thermal regulatory homeostasis is lost thus responses such as shivering, sweating, and panting should be absent during REM.

There is also autonomic nervous system activity which varies between the two phases of REM sleep – phasic REM sleep and tonic REM sleep.

Phasic REM Sleep

Phasic REM sleep is a period of REM sleep characterized by bursts of eye movements, muscle twitches, and other physiological changes. There is an increase in sympathetic activity in intermittent bursts during phasic REM. This causes fluctuations in blood pressure, heart rate, cardiac output, coronary artery blood flow, and cardiac metabolic activity as well as causes brady-tachycardia arrhythmias. There is pupil dilation due to cortical inhibition of parasympathetic outflow to the iris. Irregular breathing patterns are exhibited. While diaphragmatic function is maintained, there is intercostal muscle atonia and a decrease in upper airway muscle tone (causes upper airway resistance). Metabolic input for Pa02 and PaC02 through the carotid bodies and central chemoreceptors is blunted. A profound increase in sympathetic activity will be seen in vessels, innervating skin and muscles.

Tonic REM Sleep

In contrast to Phasic REM sleep, Tonic REM sleep is a period of REM sleep that is characterized by a lack of eye movements, decreased EEG amplitude, and atonia. Increased parasympathetic and decreased sympathetic activity during tonic REM lead to a decrease in cardiac output, blood pressure, and heart rate as well as pupillary constriction due to parasympathetic drive.

The autonomic instability that occurs during both REM phases of sleep is clinically relevant, particularly when it is tied in with obstructive sleep apnea. During obstructive sleep apnea, there is chronic sympathetic hyperactivity which is linked to hypertension, cardiac ischemia, heart failure, and stroke. Of note, obstructive sleep apnea is now the third leading risk factor for stroke, independent of hypertension, diabetes, and atrial fibrillation.

Polysomnographic Findings During REM

When measured during sleep, brain waves show clear patterns associated with each sleep stage. In REM sleep, brain activity accelerates, showing markedly different types of brain waves. The EEG will return to a relatively low-voltage mixed frequency pattern. No sleep spindles, K-complexes, or NREM findings will be seen. The chin EMG will also fall to its lowest level. The classic finding will be seen on EOG channels that will show rapid eye movements. Other sleep architecture we see during REM sleep include Sawtooth EEG waves (7-8 Hz in the posterior dominant region) as well as basic muscle twitches.

Summary

As we conclude this review of the physiology of REM sleep, a sleep stage characterized by rapid eye movements, heightened brain activity, and muscle atonia, you can see how REM involves both sympathetic and parasympathetic nervous system activity. The resulting fluctuations in heart rate, breathing, blood pressure, neurotransmitters, and various reflexes highlight the autonomic instability caused during REM. This instability is clinically relevant for sleep conditions like obstructive sleep apnea and REM Behavior Disorder.

Part two of this article, which will be published in the summer issue, will review the fascinating pathophysiology of REM Behavior Disorder. Sleep video links will be available to review actual cases of RBD, and lastly, an update on treatment and management will be provided in detail.