Presentation on theme: "Physiology of Sleep BLOCK 3 –"— Presentation transcript:
1 Physiology of Sleep BLOCK 3 – 2011-12 Robert R. Terreberry, PhDRoom 142 Ph
2 EEG Scalp Electrodes Diagnosis of disease Determination of brain death EpilepsyDetermination of brain deathDistinguish stages of sleepRecording of electrical activity from the cerebral cortex by putting electrodes on the scalp.The EEG is primarily caused by electrical activity of the areas of the cortex just below the scalp.What type of activity in the cortex (action potentials or graded potentials) are largely responsible for the EEG? Hint - which area of the brain (white matter or gray matter) is closest to scalp?Answer: Gray cortex neuronal potential just below the scalp is what EEF is measuring.Know the weird spikes (like around F7) are seizures where you have over-firing
3 Types of EEG Waves Alpha waves Beta waves Theta waves Delta waves Frequency 8-13 Hz, moderately low voltage (50 mV)Beta wavesFrequency Hz, lower voltageTheta wavesFrequency 4-7 Hz, higher voltageDelta wavesVery low frequency (< 4 Hz),very high voltage (approx. 100 mV)DO not memorize the values verbatimHowever, you should know the trends of frequency and voltageHighest to lowest voltage: Delta>Theta>Alpha>BetaHighest to lowest frequency: Beta>Alpha> Theta>Delta (voltage backwards)Terreberry’s notes:Types of EEG WavesVariation in the frequency and amplitude of the EEG waves can be related to changes in the level of cortical activity.The normal EEG will display one or more of the following brain wave typesAlpha wavesRhythmic waves with frequencies of 8-13 Hz and moderately low voltage (50 μV)They are characteristic of patients that are awake, but resting quietly (relaxed)Beta wavesLower voltage and higher frequency (14-50 Hz)During activation of the cortex in the awake patientObserved primarily when actively concentrating (e.g., on a problem)Theta wavesHigher voltage waves with frequencies of 4-7 HzMost frequently recorded in children (and primarily recorded from the parietal and temporal areas) and in adults experiencing frustration and disappointmentAlso recorded in during stages 2 through 4 of slow-wave sleep and in bursts during REM sleepDelta wavesVery slow (less than 4 Hz), high voltage wavesIn normal subjects, recorded in stage 3 slow-wave sleep and especially during stage 4 slow-wave sleepAlso characteristic of coma
6 Waveforms - Waking State Realize that in reality, we constantly have some neurons firing, and then some off (hence the on/off pattern of the waves)When a seizure occurs all the neurons turn on all at once (this can be just in one area of the brain if a focal seizure, or it can be the entire brain if generalized)Alpha – person relaxedBeta – when awake and concentrating on something (like now…maybe haha)
7 Stages of Slow-Wave Sleep Stage 1 – Transition between asleep and awakeStage 2 – Light sleepStage 3 – Deep sleepStage 4 – Very deep sleepThe Waking State:Behaviorally, the waking state ranges from relaxed and inactive to very active.The prominent EEG wave of an awake, relaxed adult (generally with eyes closed) is the alpha waveWhen the eyes are opened and the person is attentive to external stimuli (or is concentrating hard with eyes closed), alpha waves are replaced by beta waves.Stages of Sleep -Sleep is not simply a state of decreased neural and physical activity, as once thought. Sleep consists of several distinct, complex neurophysiological stages.The two major types of sleep are slow-wave sleep and REM (paradoxical) sleep:1. Slow-Wave or Non-REM (NREM) SleepConsists of four stages of increasingly deeper sleepEach successive stage of slow-wave sleep has an EEG pattern characterized approximately by a progressively slower frequency and higher amplitude
8 Slow-Wave SleepFrequency goes down, amplitude goes up at you go into deeper sleep. Start with alpha, end with thetaNote the characteristic spindles (a) and some K complexes in stage 2 (circled in red) = bursts of activity in this stage. No one is really sure what they representStage 1 SleepAlpha waves disappear and are replaced by low-voltage mixed frequency wavesThoughts become dissociated, but subjects are easily aroused by low-intensity stimulationThis is a transitional stage from between drowsy (but awake) and light sleepThus, some experts do not even classify it as sleep at allStage 2 SleepA "light" sleep characterized by low-voltage, mixed frequency wavesCharacterized by occurrence of sleep spindles and K complexesSleep spindles are short bursts of alpha rhythmsK complexes are single large biphasic deflectionsStage 3 SleepA deep sleep in which large amplitude waves (Delta waves) with a frequency generally of < 2 Hz are observed 20-50% of the time.Stage 4 SleepA deep sleep in which large amplitude delta waves are observed more than 50% of the time.During stage 1, the eyes have a slow rolling movement; in stages 2 through 4 they are relatively motionless. Other skeletal muscles are active during stages 1 through 4.
9 REM Sleep Paradoxical or REM Sleep At each end of the slow-wave sleep cycle person goes into a short period of sleep that is the deepest, yet shows some paradoxical behaviorDuring this period the EEG pattern looks similar to the wide-awake pattern (beta waves) even though the person is generally dreaming during REM sleep (Fig. 5)Additionally, it is difficult to arouse the person from REM sleep, yet the person is more likely to spontaneously awaken during REM sleep than during slow-wave sleepREM sleep is characterized by rapid-eye movements (REM), irregular heart rate and respiration, and story-like dreaming.
10 Sleep-Wakefulness Stages BehaviorEEGAlert wakefulnessAwake, alert with eyes openBetaRelaxed wakefulnessAwake, alert with eyes closedMainly alphaRelaxed drowsinessFatigued, tired, bored; head may droop; lapses of attention. Sleepy but not asleepMainly alpha, but amplitude and frequency decreased
11 Sleep-Wakefulness Stages BehaviorEEGStage 1Very light sleep, easily aroused; neck jerksMixed – alpha, theta, a few deltaStage 2Light sleep; but less readily arousedMixed; sleep spindles (a) and some K complexesStages 3 & 4Deep sleep, difficult to arouse in 4Theta and delta; mainly delta in 4
12 Sleep-Wakefulness Stages BehaviorEEGParadoxical (REM) sleepDeepest sleep, yet spontaneously awaken; lasts about 10 min every min. Dreaming, rapid eye movements, increased brain O2 consumptionBeta – looks like awake, alertAs the sleep cycle goes on the % of REM increases
13 New Sleep Nomenclature Stage W = WakefulnessStage N1 & Stage N2 = “Light sleep”Stage N3 = “Deep sleep”(combines classic Stages 3 & 4)Stage R = “Active” REM sleepWill use slow wave 1,2,3,4 and REM on the testDon’t worry about this other than from a clinician’s perspective
14 Sleep Architecture Sleep Architecture Throughout sleeping a normal person cycles between slow-wave sleep and REM sleep several times during a typical 8 hr sleep periodThe pattern of these cycles is referred to as "sleep architecture"Note that sleep stages 3 and 4 are much more likely during the first few hours of sleep, and that REM sleep is more frequent late in the sleep period (morning hours)Thus, if total sleep time is shortened, REM sleep is disproportionately reducedAge also has an important role in determining sleep architectureTotal sleep time decrease with ageBut the % of REM will stay constant regardless of how much you sleep (given that you sleep this pattern on a regular basis…ie NOT us)Relative percentage of REM versus slow-wave sleep changesIn newborns REM sleep accounts for 50% of the total sleep timeBy about age 20, REM sleep accounts for only about 20% of the total sleep time regardless of how long you sleep (if you get a regular pattern of sleep)After age 20, total sleep time continues to decline, but the percentage of REM versus slow-wave sleep remains about 20% REM, 80% slow-wave sleep (if you get a regular pattern of sleep)YOU CANNOT just sleep longer at another time to “make up” for lost sleep b/c your REM is so much less during initial sleepREM is critically impt for consolidation of memories from short term long term.
15 Physiological Changes During Sleep Skeletal muscleActivity declines during slow-wave sleep; tonic inhibition during REM sleep, except for eye and respiratory musclesCardiovascular and RespiratoryActivity declines during slow-wave sleep; wild oscillations during REM sleep (sometimes life-threatening)Terreberry specifically said “I think these two things are important to remember”…know this slide well.1. Skeletal MuscleSkeletal muscle activity declines during slow-wave sleep. During most of REM sleep, there is a general tonic inhibition of skeletal muscle activity, which is nearly complete except for some notable exceptions.One exception, noted earlier, is the eye muscles; during REM sleep, rapid bursts of eye movements occur. The motor neurons to the primary muscles of respiration (esp. diaphragm) also normally escape the generalized inhibition.Additionally, periodically occurring twitches and muscular tremors of the face and limbs frequently occur during REM sleep. Thus, during REM, periodic bursts of excitatory activity break through the generalized tonic inhibition.2. Cardiovascular and Respiratory SystemsDuring slow-wave sleep there are relatively steady decreases in blood pressure, heart rate, and respiratory rate.Metabolism needs are lower so respiratory needs are lowerIn contrast, REM sleep is associated with general increases and large oscillations in blood pressure, heart rate and respiratory rate. Very high phasic blood pressures experienced during REM sleep have been associated with strokes and heart attacks.For 70 years it has been known that fatal heart attacks are most common from 5-6 a.m., when most people are in longer cycles of REM sleep.People stroke outOther information in Terreberrys notes (he didn’t discuss these):EndocrineDuring slow-wave sleep, there are pulsatile releases of growth hormone and the gonadotropic hormones from the anterior pituitaryIn children, growth hormone is secreted exclusively during sleep. Growth hormone secretion in children generally peaks during early portion of the sleep period, during non-REM stages 3 and 4. However, during puberty and adolescence, patterns of secretion change. Though the major peak generally still occurs during sleep, several other peaks occur throughout the day.Prolactin secretion occurs almost entirely during sleep, with secretion being maximal in the early morning hoursCortisol secretion reaches its minimum early in the sleep period and peaks at the end of the sleep periodThyroid-Stimulating Hormone (TSH) secretion peaks prior to the onset of sleep and then declines during sleepLuteinizing Hormone (LH) drives male testosterone production. LH increases during sleep are responsible for male puberty. In adult males LH secretion is less related to sleep.Follicle Stimulating Hormone (FSH) follows a similar pattern as LH. During female puberty LH and FSH peak during sleep 4. OtherBody temperature exhibits a highly stable circadian (approx. 24 hr) rhythm. As the night progresses, the core body temperature falls, reaching its minimum during slow-wave sleep in the early morning hours. During REM sleep, however, body temperature increases slightly.Changes in renal function also occur during sleep, characterized by a decrease in urine volume and increased osmolality
16 Functions of Sleep Slow Wave REM Sleep Rest and Restoration? Physical changes necessary for learning and memoryMental healthFunctions of SleepWhy do we need sleep? It really isn't clear.Traditional view that sleep is necessary to "rest" the brain and/or body, is not the total answerSlow-wave sleep may largely serve as a time of the body's rest and metabolic restoration.But even during slow-wave sleep, some functions are enhanced.REM sleep is thought to be needed for the physical changes necessary for long-term memory and learning.REM sleep may be needed to sort through short-term memory stores, deleting unnecessary data and the chemical and structural changes necessary for transferring important information into long-term memoryBabies sleep more perhaps because they need time to develop new connections, etc.REM sleep may also allow for the expression, through dreams, of "subconscious" anxieties and concernsPeople who don't get enough REM sleep have hallucinations, often disturbing in nature.You cannot “store up” and “make up” for lost sleep and regain that time of lost REM
17 Sleep Areas of the Brain The sleep-wake cycle and passage through the various stages of sleep are controlled by the cyclical action of different systems of the hypothalamus and brain stem.The circadian rhythm of approximately 8 hr sleep and 16 hr awake is due to the cyclical nature of the interaction of these systemsSleep Areas in the Brain - Sleep is actively induced and modulated by a number of centers within the brainSuprachiasmatic nucleus of the hypothalamusThe basic circadian rhythm is controlled by the biological clock located in the suprachiasmatic nucleus of the hypothalamusReceives input from retinal and other inputs which modulate circadian rhythmThus, the body "clock" is affected by environmental cues (particularly light/dark cycles through hormone melatonin). Jetlag and working alternating shifts confuses these cuesA major determinant of sleep-wake rhythms are the interactive systems, largely in the brainstem, one an arousal system and the other an inhibitory sleep-promoting system. Thus, neurons in some brainstem regions are most active during waking and are inhibited during sleep, while neurons in other regions show the opposite activity pattern.Arousal systems in the brainCholinergic neurons in the upper pons activate thalamic nuclei and adrenergic neurons in the upper brainstem stimulate the cerebral cortexPeptidergic neurons in the hypothalamus, containing orexins (hypocretins) and melanin concentrating hormone also activate thalamic nuclei, and stimulate the cerebral cortex and brainstem arousal areasThe arousal system of the brainstem (largely the Raphe Nuclei) is part of the Reticular Activating System (which sets the general level of arousal/alertness)This is area in which amphetamines act to promote arousal and decrease sleepExcitatory neurons (which release norepinephrine or serotonin) in the Reticular Activating System, which are active during the waking state, lead to arousal and enhanced attention to the outside worldThe excitatory neurons also inhibit cholinergic brainstem neuronsDuring waking, the excitatory neurons dominate, whereas during REM sleep the cholinergic neurons are dominant
18 Sleep Areas - Hypothalamus Suprachiasmatic NucleusSets basic circadian rhythmVisual inputs importantPreoptic Area of HypothalamusGABA promotes slow-wave sleepInhibits excitatory pathwaysPosterior HypothalamusHistamine promotes wakefulnessProbable site of antihistamine actionSleep systems in the hypothalamusInhibitory neurons in the preoptic nucleus of the hypothalamus inhibit arousal areas of the brainstemOrexin-containing neurons in the lateral hypothalamus activate arousal areasHistamine-containing neurons in the posterior hypothalamus project to the Reticular Activating System and promote wakefulnessThe drowsiness associated with anti-histamines is thought to be due to inhibition of these neurons
19 Sleep Areas - Brainstem The Arousal SystemRaphe nucleus of Reticular Activating System (sets overall arousal/alertness)Slow-Wave Promoting SystemNucleus Tractus SolitariusREM Promoting SystemPontine tegmentum; superimposes REM on slow-wave sleepREM-promoting areasAreas in the brainstem (pontine tegmentum and ventrolateral periaqueductal gray) are largely responsible for the cyclical imposition of REM sleep upon slow-wave sleepIf you LESION the PONS you could never go into REM death eventually
20 Sleep-Promoting Factors ProstaglandinsPeptidesVIP, hypocretins, DSIPCCKSleepiness after large meal??MelatoninSecreted by pineal gland. Acts on suprachiasmatic nucleus. Treats insomnia in elderly, jet lag.In addition to the classical neurotransmitters (ACh, serotonin, NE, etc.), several (>30) other sleep-promoting and sleep-inhibiting factors have been suggested to contribute to the sleep-wake cycle, among themProstaglandins (PGD2 - sleep, PGE2 - wakefulness)PeptidesEspecially VIP, hypocretins and Delta Sleep-Inducing Peptide (DSIP). The latter induces delta waves. DSIP does not initiate sleep, but keeps sleep/wake cycle in proper orderHypocretins (orexins)Peptides discovered in 1998 that are released from neurons whose cell bodies are largely located in the lateral hypothalamus, but whose axons project throughout the brainThey are very similar in structure to the GI hormone secretin and they stimulate appetiteRecently shown to activate thalamic nuclei, and stimulate the cerebral cortex and brainstem arousal areasLipopolysaccharideInterleukin-1Interferon-alpha-2Tumor necrosis factorSerotoninCholecystokinin (CCK)Probably contributes to drowsiness associated with a large mealADH – may promote REM sleepMelatoninHormone secreted by the pineal glandActs on the suprachiasmatic nucleus via specific receptors that lead to gene transcription of proteins involved in circadian rhythmsMelatonin has been shown to be useful in treatment of jet lag and insomnia in the elderly (probably because melatonin production decreases with age), but not as a general “sleeping pill”
21 Sleep Pathologies DIMS DOES Dysomnias Parasomnias Disorders initiating and maintaining sleepDOESDisorders of excessive somnolenceMost common: narcolepsyDysomniasCircadian rhythm disturbancesParasomniasNightmares, night terrors, sleep walking, sleep apneaSleep disorders fall into four major categoriesDIMS"Disorders Initiating and Maintaining Sleep"Often a problem of children; associated with sleep onset associations (wrong pillow, absent teddy bear, etc.)DOES"Disorders Of Excessive Somnolence"The most common is narcolepsy, which affects about 1 in 2000 peopleNarcoleptics are chronically sleepy, and have an abnormal tendency to progress suddenly from being awake to REM sleep, often in response to a strong emotional stimulusThis abnormal REM sleep is accompanied by a sudden loss of muscle toneRecently, it has been shown that most instances of narcolepsy are associated with a loss of hypocretin-producing cells in the hypothalamusSimilarly, in experimental animals, genetically-induced hypocretin deficencies produce narcolepsyDysomniasDisturbances of the normal circadian rhythmicity of sleep (e.g., “jet lag”)ParasomniasA broad set of normally undesirable behaviors that either occur exclusively during sleep or are exaggerated by sleep.Nightmares, night terrors, sleepwalking, etc.Nightmares are story-like bad dreams that most often occur during REM sleepIn contrast, night terrors are certain types of dreams occurring during slow-wave sleep characterized by "feelings" as opposed to specific imagesDuring night terrors a person wakens abruptly, often screams and runs about disoriented and unable to speak coherentlyThe episode lasts 3-4 minutes, then the person goes back to sleepSleepwalking can involve fairly complex motor behaviors while the person is in slow-wave sleepSleep apneaSleep is characterized by frequent periodic breathing pausesCentral vs. obstructive sleep apneaObstructive sleep apnea is caused by a physical blockage of the airway, usually due to collapse of soft tissue in the rear of the throat. It is often associated with obesityCentral sleep apnea is caused by REM skeletal muscle inhibition extending to respiratory muscles too
22 Pharmacology of Sleep – Sleep Promoting AlcoholHypnotics – prescription sleeping pillsAnti-histamines – OTC sleeping pillsDSIP – maintains normal sleep architectureSleep PromotingAlcoholCan cause insomnia; although more frequently induces sleep due to relaxationHypnoticsPrimarily sleep-inducing (prescription "sleeping pills")Anti-histaminesMost over the counter sleeping pills.DSIP (Delta Sleep-Inducing Peptide)Given to insomniacs, maintains proper sleep architecture.
23 Pharmacology of Sleep – Sleep Inhibiting CaffeineCommon cause of insomniaAmphetamines & cocaineStimulants that suppress REM sleepClassic treatment for narcolepsyNewer non-amphetamine drugs with fewer side-effects now available for narcolepsyCaffeineA common cause of insomniaCan cause decreased sleep for 8-14 hrAmphetamines/CocaineSuppress REM sleepNarcoleptics traditionally were most often treated with stimulants such as amphetamines, or with antidepressantsIn the past few years, newer non-amphetamine stimulants with fewer side effects, have begun to be used for the treatment of narcolepsy