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Lecture 15

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University of Toronto Scarborough
Biological Sciences
Stephen Reid

1    Lecture 15: Sleep, and Sleep-related Breathing Disorders 1. Electroencephalography (ECG) Waves Sleep can generally be defined by looking at ECG (electroencephalogram) brain wave patterns. There are four general categories of ECG waves: alpha, beta, theta and delta. Alpha waves, with a frequency of about 10 Hz occur when people are awake but generally relaxed with their eyes closed. Alpha wave frequency decreases with wakeful activity. Beta waves, with a frequency of approximately 14 to 30 Hz, are produced by visual stimulation and mental activity. Theta and delta waves are much slower, and occur primarily during sleep. Theta waves, from about 4-8 Hz, are not often seen during wakefulness unless the person is under severe mental stress or is day-dreaming. Delta waves, which have a frequency below 4 Hz, are prominent during sleep but are rare and generally pathological when a person is awake. ECG is a useful tool for diagnosing brain activity during sleep, but ECG biofeedback can also be used to treat attention deficit disorder and various anxiety disorders. A patient will look at a screen displaying the various wave components of the patient's ECG activity. They then train themselves to produce more of one type of wave or another. For example, a patient with ADD can learn to produce more beta waves (associated with concentration) and fewer theta waves (associated with daydreaming). A patient with an anxiety disorder can learn to produce less beta wave activity and more alpha waves (associated with relaxation). 2. Why do we sleep? The exact purpose of sleep remains a mystery - it was once thought that wakefulness was the 'active' state of the mind, but it is now known that the brain can remain very active during sleep. What we can say generally is that sleep is a cyclically occurring state of decreased motor activity and perception, and that is occurs in various stages in which neurons go from being very quiescent, to extremely active. Regarding the purpose of sleep, the most we can gather is that it may be needed for brain maturation during development, to strengthen synaptic connections, or to enhance the immune system. There are various stage of sleep and a number of regions in the 2    brain that are known to be involved in producing these various sleep stages. In the raphé nucleus there are cells that appear to regulate (at least in part) REM sleep; in the pre-optic area of the hypothalamus there are neurons that are important for slow-wave sleep generation; and the entire reticular formation appears to be important for regulating wakefulness or arousal. 3. Slow-Wave Sleep and Rapid Eye Movement (REM) Sleep ECG activity can allow one to determine what stage of sleep a person is experiencing. From wakefulness, we go into what is termed slow-wave sleep (SWS), which itself consists of four stages - and from there into REM sleep. We then cycle between slow-wave and REM sleep during the course of the night (or sleep period). As the night (sleep period) progresses, we spend proportionally more time in REM sleep and less in SWS, particularly in stages 1 and 2. There are some essential differences between SWS and REM sleep. Slow-wave sleep produces low frequency ECG waves, there is decreased muscle tone, and for the most part decreased brain activity (though parasympathetic activity increases). Though most dreams occur in REM sleep, a few can happen during slow-wave sleep, and these tend to be more logical. Snoring can also occur during slow-wave sleep. REM sleep, in contrast, produces high frequency ECG activity that looks very much like those produced during wakefulness. The postural muscles become paralyzed, though the facial and limb muscles still twitch. The eyes move rapidly (REM; rapid eye movement), and it is generally believed that the movement of the eyes mirrors the direction a person is looking whilst dreaming. If a person snores, it stops during REM sleep. The brain becomes very active, and it is during REM sleep that emotionally narrative, though not necessarily logical, dreams occur. A person is much more likely to remember dreams had during REM sleep than dreams from slow-wave sleep though, regardless, 95% of dreams are forgotten upon waking. When we are awake, the ECG trace shows primarily low-voltage, high frequency beta waves. As we begin to rest, alpha wave activity occurs, and brain activity becomes more rhythmic and synchronized. By stage 2 of slow-wave sleep, theta waves become more prominent, though they 3    are interspersed with 'sleep spindles', which are short bursts of alpha wave activity. Stage 3 shows a mix of theta and delta wave activity, and in the deepest stage of slow-wave sleep, stage 4, delta waves dominate. The brain then returns to the earlier stages of SWS before entering into REM sleep which is a sleep state in which the ECG is similar to that seen in wakefulness. The ECG trace in REM sleep is composed mostly of beta waves - just like being awake. 4. Narcolepsy Narcolepsy is a neurological disorder of sleep/wakefulness regulation. It consists of the intrustion of REM sleep into wakefulness, and it diagnosed by four key symptoms: excessive daytime sleepiness, cataplexy (sudden, brief episodes of muscle weakness or paralysis brought upon by strong emotion), sleep paralysis, and hypnagogic hallucinations (vivid, dream-like images at sleep onset). On an ECG trace we can see how, from the onset of cataplexy to the end, activity in the locus coeruleus ceases, whilst neurons in the medial medulla become active. Muscle tone (for example, in the neck) is lost, sometimes only slightly, though in other cases completely. Cataplexy is quite a different condition than narcolepsy, but 70% of sufferers share both symptoms. See the following web site for video of cataplexy. The dog and the child are particularly interesting; the fish and the mouse less so. 4    5. Clinical Case Studies 5A. Case 1: Obstructive Sleep Apnea The first case deals with an obese 37 year old man who is affected by hypertension during the day, and perhaps as a complication of his obesity, snores and suffers from difficulty breathing at night - what we term obstructive sleep apnea. He is sleepy during the daytime, leading to poor work performance and auto accidents. He also suffers from chest pain and a rapid heart rate. The traces illustrate recording taken from this patient in a sleep clinic. The first point of note are the repetitive drops in arterial O levels (arterial O saturation) during sleep. When the airway is 2 2 obstructed, no oxygen is reaching the blood, so O level2 drop, and only rise when the person is able to breathe again. If we look at the movement of the rib cage and the abdomen we see that the patient is trying to breathe however these respiratory efforts are ineffective. The attempts at breathing suggest that respiratory control systems are intact - his respiratory muscles, chemoreceptors and nervous control systems are working normally – but, for the most part, air is prevented from getting into his lungs by a physical blockage or by a collapsed airway. We know his chemoreceptors are functional because each time he attempts a breath, the next attempt is even more forceful, meaning that his chemoreceptors are sensing rising CO 2 levels, causing the increased respiratory 5   
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