Task 6 - Sleep PDF

Task 6 - Sleep Learning Goals What are the different stages of sleep? Why do we sleep? - added by me, was in >1 book How does our internal clock function? What can happen when it does not function well? What is the underlying neurological basis of sleep? What is the role of hormones in sleep? What...

Task 6 - Sleep Learning Goals What are the different stages of sleep? Why do we sleep? - added by me, was in >1 book How does our internal clock function? What can happen when it does not function well? What is the underlying neurological basis of sleep? What is the role of hormones in sleep? What are different types of sleep disorders? What are the different stages of sleep? The different stages of sleep are divided according to patterns in 3 standard psychophysiological measures: EEG, electrooculography (EOG), which measures eye movements and electromyography (EMG), which measures muscle electrical activity. EEG patterns Synchronous EEG activity (a)- if neurons are active at about the same time, their electrical messages are synchronized and appear as a large, clear wave in the EEG data. Desynchronous EEG activity (b) - if neurons are active at random, their electrical messages are desynchronized and cancel each other, resulting in small chaotic waveforms without a clear pattern in the EEG data. Alpha EEG activity - regular, medium frequency waves of 8-12Hz (Hz = cycles per second), produced when a person is resting quietly, not particularly aroused or engaged in strenuous mental activity. They are more prevalent when a person's eyes are closed. Beta EEG activity - irregular, mostly low-amplitude waves of 13-30Hz. Beta activity shows desynchrony, which reflects the active processing of information by many different neural circuits in the brain. Desynchronized activity occurs when a person is alert and attentive to events in the environment or is thinking actively. The 3 stages of sleep EEG After eyes are shut and a person prepare to sleep => alpha waves begin to come in place of the low-voltage high-frequency waves of alert wakefulness. As the person falls asleep, there is a sudden transition to a period of stage 1 sleep EEG, which is characterized by low-voltage, high-frequency signal, similar to, but slower than that of alert wakefulness. Initial stage 1 EEG - the first stage 1 EEG during a night's sleep. Marked by theta activity (3.5-7.5Hz), which indicates synchronization of neurons in the neocortex. Not marked by any significant electromyographic or electrooculographic changes. A person may experience hypnic jerks - muscle contractions followed by relaxation. They might be accompanied with a falling sensation. Emergent stage 1 EEG (REM sleep) - subsequent periods of stage 1 sleep EEG. Marked by theta and beta activity, rapid eye movements (REMs), a loss of tone in the muscles of the body core (person becomes paralyzed), high cerebral activity in many brain structures, a general increase in the variability of autonomic nervous system activity. Also, occasional muscle twitches happen and there is almost always some degree of erection. During REM sleep, a person is easily aroused by meaningful stimuli (e.g. sound of their name). Also, when awakened from REM sleep, a person appears alert and attentive. Stage 2 sleep EEG has a slightly higher amplitude and a lower frequency than stage 1 EEG. It is also accompanied with 2 characteristic wave forms: K complexes - sudden, sharp waveforms. They spontaneously occur once per minute but can be triggered by noises Sleep spindles - 0.5-2s bursts of 11- to 15-Hz waves that occur between 2 and 5 times a minute. Increase numbers of sleep spindles are correlated with increased IQ scores. Stage 3 sleep EEG is defined by a predominance of delta waves - the largest and slowest EEG waves, with a frequency of 1 to 2 Hz. For this reason it is also referred to as slow-wave sleep (SWS). Here we observe EEG synchrony. This is the deepest stage of sleep, because only loud noises will cause a person to awaken, and when awakened, the person acts groggy and confused. After stage 3 EEG, sleepers retreat back through the stages of sleep to stage 1. Initial stage 1, stage 2 and stage 3 are sometimes referred to as NREM 1, NREM Body and Behavior Page 1  Initial stage 1, stage 2 and stage 3 are sometimes referred to as NREM 1, NREM 2 and NREM 3 (non-REM ). After the first cycle of sleep EEG (from initial stage 1 to stage 3 to emergent stage 1), the rest of the night is spent going back and forth through the stages. Each cycle is about 90 minutes long. As the night progresses, more and more time is spent in emergent stage 1 sleep and less time is spent in the other stages, especially in stage 3. There are also brief periods during the night when the person is awake, which are usually not remembered in the morning. Dreaming People who have just awoken from REM sleep are more likely to recall dreams and the dreams recalled are stories rather than isolated experiences (which is what is usually recalled from NREM sleep). However, it is well established that dreaming occurs during NREM sleep. In the later NREM stages, dreaming can also have a storyline. Also, specific cortical lesions can abolish dreaming without affecting REM sleep, suggesting that REM sleep and dreaming can be dissociated. External stimuli (some more than others) are sometimes incorporated into our dreams. Examples of stimuli that are likely to be incorporated are water droplets and the feeling of pressure on a limb. Dream content is influenced by what is experienced in the prior period of wakefulness (even boring experiences). The amount of anxiety experienced before a period of dreaming affects the emotional content of dreams. Latest research on dream duration supports the idea that dreams run slightly slower than real time, contrary to the popular opinion that dreams are almost instantaneous. Sleeptalking (somniloquy) has no special association with REM sleep - it can occur during any stage but most often occurs during the transition to wakefulness. Sleepwalking (somnambulism) occurs during slow-wave sleep, and never during REM sleep, when core muscles tend to be completely relaxed. Lucid dreaming - the ability to be consciously aware that one is dreaming and, in some cases, be able to control the content of one's dream. The likelihood to have a lucid dream can be increased by transcranial electrical stimulation to the dorsolateral prefrontal cortex, some cognitive training techniques and ACh agonists. The brain changes associated with lucid dreaming are not yet established (study results are contradictory). Theories of why we dream Hobson's activation-synthesis hypothesis - during sleep, many brainstem circuits become active and send output to the cerebral cortex. Information supplied to the cortex during sleep is largely random and the resulting dream is the cortex's effort to make sense of these random signals. Revonsuo's evolutionary theory of dreams - we dream to simulate threatening events in order to better predict and respond to threats when we are awake => dreaming has an evolutionary advantage. Hobson's protoconsciousness hypothesis - we dream to simulate any events, not only threatening ones. Dreaming is a training mechanism, with each dream representing a virtual real-life scenario. Protoconsciousness - a virtual prototype of our conscious experiences. This contradicts Hobson's former theory. Neurological basis of dreaming Bilateral lesions in the temporo-parieto junction or the medial prefrontal cortex lead to cessation of dreaming. Lesions to the secondary visual cortex in the medial occipital lobe lead to a loss of visual imagery in dreams. The medial prefrontal cortex, medial occipital cortex and the temporo-parieto junction display increased neural activity during REM sleep. The temporo-parietal junction is associated with both REM and NREM dreaming => it is critical for dreaming in general. During dreaming, the activity in the prefrontal cortex is low, which reflects the lack of organization and planning in dreams. Why do we sleep? Recuperation theories of sleep - being awake disrupts the homeostasis (internal physiological stability) of the body and sleep is required to restore it. The brain needs to rest periodically to recover from adverse side effects of its waking activity. One of these effects is the waste products produced by the high metabolic rate associated with its waking activity. Prolonged sleep deprivation causes an increase in these chemicals. During slow-wave sleep the lowered rate of metabolism permits restorative mechanisms in the cells to destroy the chemicals and prevent their damaging effects. Body and Behavior Page 2  lowered rate of metabolism permits restorative mechanisms in the cells to destroy the chemicals and prevent their damaging effects. Adaptation theories of sleep - sleep is not a reaction to the disruptive effects of being awake, but the result of an internal 24-hour timing mechanism. We are highly motivated to engage in sleep (e.g. to conserve resources, carry out brain functions which are impossible during wakefulness, make ourselves less susceptible to incidents in the dark), but we don't need it to stay healthy. Most mammals and birds sleep => suggests that sleep serves an important physiological function, rather than merely offering protection from incidents (some species are at increased risk of predation when they sleep) and energy conservation (some species have evolved complex mechanisms that enable them to sleep). => suggests that it is not likely that the primary function of sleep is a special higher-order human function. Effects of sleep deprivation Sleep deprivation is usually coupled with stress, making it hard to interpret results of studies on it. Sleep-deprived individuals report being more sleepy and fall asleep more quickly if given the opportunity. Sleep-deprived individuals display negative affect on various tests of mood. Sleep-deprived individuals perform poorly on tests of sustained attention. The effects of sleep deprivation on complex cognitive functions depend on the type of cognitive function. Logical deduction and critical thinking seem to be immune to disruption by sleep deprivation. Executive function (problem solving, working memory, decision making, assimilating new information to update plans and strategies) is impaired by sleep deprivation. The study of the effects of sleep deprivation on physical performance is controversial (contrary to the popular belief that sleep is essential for good motor performance). Sleep deprivation leads to reduced body temperature, increases in blood pressure, decreases in some types of immune function, hormonal and metabolic changes. Sleep-deprived people become more efficient sleepers: the time to fall asleep after going to bed decreases; the number of nighttime awakenings decreases; the sleep has a higher proportion of slow-wave sleep, which is believed to serve the main restorative function. After sleep deprivation, only a small proportion of total lost sleep is regained. However, most of the SWS is regained. After sleep deprivation, the SWS EEG is characterized by an even higher proportion of slow waves than usual. People who sleep =8hrs/night. Long-term studies of sleep reduction show that there are no marked deficits in people whose sleep was reduced with a few hours. Microsleep - brief periods of sleep, typically 2-3s long, during which the eyes close and the individuals are less responsive to external stimuli, even though they remain sitting or standing. After 2-3 days of continuous sleep deprivation, most research subjects experience microsleeps. REM-sleep deprivation leads to a REM rebound (subjects have more than their usual amount of REM sleep for the first 2-3 nights) and more frequent initiation of REM sleep => suggests that there is a need for a certain amount of REM sleep. Default theory of REM sleep - it is difficult to stay continuously in NREM sleep, so the brain periodically switches to one of two other states: If there are any immediate bodily needs to be taken care of, the brain switches back to wakefulness. If there are no immediate needs, it switches to REM sleep. => REM sleep is more adaptive than wakefulness when there are no immediate body needs. Study: awakening adults upon entering REM sleep and keeping them awake for 15 minutes for each lost period makes them not display REM rebound or tiredness the next day. Antidepressants, which reduce REM sleep, increase the number of nighttime awakenings. Sleep and learning Declarative/explicit memories - memories that people can talk about (e.g. past episodes in one's life) or relationships between stimuli (e.g. spatial relationships between landmarks that facilitate navigation in one's environment). Slow-wave sleep facilitates consolidation of declarative memories. The hippocampus plays a role in navigational learning. During slow-wave (* but not REM) sleep, specific patterns of hippocampus activation suggest that rehearsal of newly learned navigational information occurs during slow-wave sleep. Nondeclarative/implicit memories - memories gained through experience that do not necessarily involve an attempt to memorize information (e.g. learning to drive a car, catch a ball or recognize a person's face). REM sleep facilitates consolidation of nondeclarative memories. How does our internal clock function? What can happen when it does not function well? Circadian rhythm/cycle - a cycle in behavior and physiological processes that repeats itself roughly every 24 hours. Entrainment - the process of synchronizing a biological rhythm to an environmental stimulus. Zeitgebers - temporal cues in the environment (e.g. the light) that synchronize the schedule of (entrain) our circadian cycles. Humans and other animals maintain their circadian rhythms under conditions in which there are absolutely no temporal cues. Free-running rhythms - circadian rhythms in constant environments. Free-running period - the duration of a free-running circadian rhythm. The free-running period in humans is on average 24.2 hours in humans living under constant illumination. Most animals display a circadian cycle of body temperature that is related to their circadian sleep-wake cycle: they tend to sleep during the falling phase of their circadian body temperature cycle and awaken during its rising phase. Internal desynchronization - when subjects are housed in constant lab conditions, their sleep-wake and body temperature cycles sometimes break away from one another. Jet lag - acceleration/deceleration of the zeitgebers that control the phases of various circadian rhythms during east-bound flights (phase advances) and west-bound flights (phase delays) respectively. Body and Behavior Page 3 (phase delays) respectively. In shift work, zeitgebers do not change, but workers are forced to adjust their natural sleep-wake cycles in order to meet the demands of changing work schedules. Both jet lag and shift work produce sleep disturbances, fatigue, general discomfort, and deficits on tests of physical and cognitive function. These disturbances can last for many days. For example, it takes ~8 days to completely adjust to the phase advance of 8 hours caused by jet lag. The problems that result from both shift work and jet lag can be solved by synchronizing the internal clock as quickly as possible to the external environment. One way to do so is to provide strong zeitgebers at the appropriate time. If a person is exposed to bright light before the low point in the daily rhythm of body temperature (1-2h before awakening), the person's circadian rhythm is delayed. If the exposure to bright light occurs after the low point, the circadian rhythm is advanced. There is evidence that the circadian clock (an internal timing mechanism) is implemented as a function in the suprachiasmatic nuclei (SCN) of the medial hypothalamus, which receives light information from the environment and uses it to entrain behaviors to a 24-hour light/dark cycle. Many SCN neurons tend to be inactive at night, start to fire at dawn, and fire at a slow, steady pace all day. The SCN reveal a direct projection from the retina to the SCN: the retinohypothalamic pathway. Melanopsin - a special photochemical that facilitates this transfer of information from the retinal ganglion cells (neurons whose axons transmit information from the eyes to the rest of the brain). People who are blind (due to loss of rods and cones in the eyes) can still show normal circadian rhythms thanks to these specialized melanopsin- containing ganglion cells in the retinas. SCN are the main circadian clocks in mammals, but they are not the only ones. Bilateral SCN lesions do not eliminate the ability of all environmental stimuli to facilitate circadian rhythms (e.g. they can block entrainment by light but not by regular food/water availability). Just like SCN neurons, cells from other parts of the body often display free-running circadian cycles of activity. There exist circadian genes that determine the duration of an animal's free-running circadian rhythms. Similar circadian genes are found in many species of different evolutionary ages => circadian genes evolved early in evolutionary history. The transcription of proteins by the circadian genes displays a circadian cycle, which is how their function is realized. Most cells contain potential molecular circadian timing mechanisms, but these are usually regulated by neural and hormonal signals from the SCN. Most mammals and human infants display polyphasic sleep cycles - they regularly sleep more than once per day. Most human adults display monophasic sleep cycles - they sleep only once per day. Naps have recuperative powers out of proportion with their duration => suggests that polyphasic sleep might be particularly efficient. Advanced sleep phase syndrome - a syndrome that causes a 4-hour advance in rhythms of sleep and temperature cycles. People with this syndrome fall asleep around 7:30PM and awaken around 4:30AM. It is caused by a gene mutation that changes the relationship between the zeitgeber of morning light and the phase of the circadian clock that operates in the SCN. Delayed sleep phase disorder - the opposite syndrome that is caused by mutations of another gene. The pineal gland is a neuroendocrine organ that is located just above the thalamus, where the 2 halves of the brain join. In response to input from the SCN, during the night it secretes a hormone called melatonin, which controls hormones, physiological processes and behaviors that show seasonal variations. Melatonin acts on receptors in the SCN, which can affect the sensitivity of SCN neurons to zeitgebers and can itself alter circadian rhythms. The administration of melatonin at the appropriate time significantly reduces the adverse effects of both jet lag and shift work. What is the underlying neurological basis of sleep? What is the role of hormones in sleep? Levels of ACh in the hippocampus and neocortex, which serve as a measure of arousal, are high while being awake and in REM sleep, but low during slow-wave sleep. Study in rats: the activation of the noradrenergic system of the locus coeruleus (LC) in the dorsal pons releases norepinephrine throughout the brain. The activity of the noradrenergic neurons in the LC is high during wakefulness, low during slow-wave sleep and almost none during REM sleep. Within a few Body and Behavior Page 4 activity of the noradrenergic neurons in the LC is high during wakefulness, low during slow-wave sleep and almost none during REM sleep. Within a few seconds of awakening, the rate of firing increases dramatically Serotonergic neurons in the raphe nuclei (in the reticular formation) are less active during slow-wave sleep and almost completely inactive during REM sleep. However, once the period of REM sleep ends, the neurons temporarily become very active again. Histaminergic neurons in the hypothalamus are highly active while awake and not very active during slow-wave and REM sleep. The posterior hypothalamus and adjacent midbrain are thought to promote wakefulness. The anterior hypothalamus (preoptic area) and adjacent basal forebrain are thought to promote sleep. When preoptic neurons become active, they suppress the activity of arousal neurons (described at the beginning of this section + orexin-synthesizing neurons - see narcolepsy in next section) and we fall asleep. Destruction of the preoptic area causes total insomnia in rats. Electrical stimulation causes drowsiness and sleep. The neurons in the preoptic area receive inhibitory inputs from some of the same regions they inhibit. This mutual inhibition may provide the basis for establishing periods of sleep and waking. Neurons in the preoptic area are inactive until an animal shows a transition from waking to sleep. Low levels of activity in the reticular formation produce sleep and high levels produce wakefulness. Because of this, the reticular formation is often called the reticular activating system. REM sleep is controlled by a variety of nuclei scattered throughout the caudal reticular formation. Each site is responsible for controlling one of the major indices of REM sleep, such as reduction of core-muscle tone, REMs, cortical EEG desynchronization etc. REM sleep, slow-wave sleep and wakefulness are not each controlled by a single mechanism. Each state results from the interaction of several mechanisms that are capable under certain conditions of operating independently of one another. During REM-sleep deprivation, penile erections, which normally occur during REM sleep, begin to occur during slow-wave sleep. During total sleep deprivation, slow waves, which normally occur during slow-wave sleep, begin to occur during wakefulness. In times of increased brain activity, astrocytes release adenosine, a nucleoside neuromodulator, which has an inhibitory effect on neural activity. The accumulation of adenosine serves as a sleep- promoting substance. During SWS, the astrocytes renew their stock of glycogen. If wakefulness is prolonged, even more adenosine accumulates, which inhibits neural activity and produces the cognitive and emotional effects that are seen during sleep deprivation. Adenosine is destroyed during slow-wave sleep. Caffeine blocks adenosine receptors, preventing the inhibitory effect on neural activity and reducing the effects of sleep deprivation. What are different types of sleep disorders? Insomnia Insomnia - all disorders of initiating and maintaining sleep. Many cases of insomnia are iatrogenic (physician-created) - mostly because sleeping pills are a major cause of insomnia. They are effective at first, but soon tolerance is usually developed. At that point the patient cannot stop taking the drug without risking experiencing withdrawal symptoms, which include insomnia. Sleep apnea - a sleep disorder in which breathing stops many times each night. The patient wakes up, begins to breathe again, and drifts back to sleep. Sleep apnea usually leads to a sense of having slept poorly and is often diagnosed as insomnia. It can also be misdiagnosed as hypersomnia because patients are not aware of their awakenings and feel sleepy during the day. Obstructive sleep apnea - results from obstruction of the respiratory passages by muscle spasms or atonia (lack of muscle tone). It often occurs in individuals who snore a lot. It can be corrected surgically or relieved by a device that attaches to the sleeper's face and provides pressurized air that keeps the airway open. Central sleep apnea - results from the failure of the CNS to stimulate respiration. Fatal familial insomnia - an inherited disorder in which humans sleep normally at the beginning of their life but stop sleeping in midlife and die 7-24 months later. Periodic limb movement disorder - a sleep disorder characterized by periodic, involuntary movements of the limbs, often involving twitches of the legs during sleep. Restless legs syndrome - a sleep disorder characterized by tension/uneasiness in the patient's legs that keeps them from falling asleep. Body and Behavior Page 5 Restless legs syndrome - a sleep disorder characterized by tension/uneasiness in the patient's legs that keeps them from falling asleep. Both PLMD and RLS are chronic and there are no effective treatments for these disorders. Hypnotic drugs - drugs that increase sleep. Benzodiazepines - which are agonists at the GABAA receptor - can be used to treat insomnia. They increase drowsiness, decrease the time it takes to fall asleep and reduce the number of awakenings => they can be effective in the treatment of occasional difficulties in sleeping. However, tolerance develops fast, normal pattern of sleep is distorted (SWS and REM decreases, NREM 2 increases) and life expectancy decreases substantially. Antihypnotic drugs - drugs that reduce sleep Sleep restriction therapy - amount of sleep is substantially reduced. After a period of sleep restriction, the amount of time spent in bed is gradually increased in small increments, as long as sleep latency (the time it takes a person to fall asleep after turning the lights out) remains in the normal range. Sleep restriction therapy is one of the most effective treatments for insomnia and it helps even for severe cases. Other nonpharmacological treatments for insomnia include CBT, progressive relaxation techniques, sleep hygiene (e.g. maintaining a consistent sleep schedule and keeping bedrooms dark, quiet and cool). Hypersomnia Hypersomnia - disorders of excessive sleep or sleepiness. Narcolepsy - a neurological disorder characterized by severe daytime sleepiness and repeated, sleep attacks (brief daytime sleep episodes) and cataplexy (recurring losses of muscle tone during wakefulness, often triggered by an emotional experience or by sudden physical effort; caused by massive inhibition of motor neurons in the spinal cord). It is not the time spent sleeping that characterizes narcolepsy, but the inappropriateness of the sleep episodes (they can happen while eating, swimming, having sex). Mild cataplexy may force a patient to sit down for a few seconds until it passes. Severe cataplexy may cause a patient to drop to the ground and remain for 1-2 minutes. People with narcolepsy often experience sleep paralysis (the inability to move just as one is falling asleep or waking up) and hypnagogic hallucinations (dreamlike experiences during wakefulness). Narcolepsy results from an abnormality in the mechanisms that trigger REM sleep. People with narcolepsy often go directly into REM sleep when they fall asleep. They also experience dreamlike states and loss of muscle tone, which are REM-sleep characteristics, during wakefulness. Narcolepsy is associated with lower levels of a neuropeptide called orexin/hypocretin. Orexin is synthesized by neurons in the posterior hypothalamus. The orexin-producing neurons project diffusely throughout the brain, but show many connections with the reticular formation. There is evidence that people with narcolepsy have high levels of a type of immune cell called a T cell, which targets hypocretin, suggesting that narcolepsy might be an autoimmune disease. The antihypnotic stimulant modafinil is effective in the treatment of some narcolepsy cases, and some antidepressants, which facilitate serotonergic and noradrenergic activity, can be effective against cataplexy. REM-sleep-related disorders Narcolepsy can also be classified as a REM-sleep-related disorder. REM-sleep behavior disorder - a sleep disorder characterized by the failure to exhibit paralysis during REM sleep. People with this disorder can act out of dreams and be potentially dangerous to themselves and those around them. Slow-wave-sleep-related disorders Nocturnal enuresis - bedwetting. Occurs mostly in children and can be cured by training methods, such as having a special electronic circuit ring a bell when the first few drops of urine are detected in the bed sheet. Pavor nocturnus - night terrors, consisting of anguished screams, trembling, a rapid pulse, and usually no memory of what caused the terror. Also occurs mostly in children and usually cures itself as the child gets older. Somnambulism - sleepwalking that is not related to REM sleep. Sleepwalkers can sometimes engage in complex behaviors while sleepwalking. Occurs mostly in children. When it occurs in adults, it appears to have a genetic component. Sleep-related eating disorder - eating during the night while one is asleep. It can lead to obesity. Responds to dopaminergic agonists and antiseizure medication. Can be provoked by drugs that treat insomnia. Body and Behavior Page 6