Introduction To Sleep For MCQs PDF

Introduction • How sleep is measured • Transitions from sleep to wakefulness and vice versa What, why and how  1/3 of our lives spent asleep.  Traditionally thought to be a time for body and brain rest and recovery – most organisms thought to show characteristics resembling sleep –high central...

Introduction • How sleep is measured • Transitions from sleep to wakefulness and vice versa What, why and how  1/3 of our lives spent asleep.  Traditionally thought to be a time for body and brain rest and recovery – most organisms thought to show characteristics resembling sleep –high central vertebrates share some characteristic patterns of neural activity that are only shown in sleep (see next point)  1928 discovery of EEG showed marked brain activation in sleep. Physiological Measure of Sleep Gold standard of measuring sleep in humans is to measure several physiological variables. As transition from wakefulness into sleep and as move through different stages of sleep, we see marked changes in the following variables:  EEG ‐ Electroencephalogram: electrical activity graph of the brain  EOG – Electrooculogram: “ocul” = eyes – measures eye movements  EMG ‐ Electromyogram: “myo” = muscle – measures muscle activity Types or stages of sleep 1. Non‐rapid Eye Movement Sleep (NREM Sleep)- broken into several stages in descending order of depth: a. Stage 1 – N1 – transition between wakefulness and sleep – Theta 4-7Hz b. Stage 2 – N2 – later stage of transition: 1st stage of true sleep – Theta with large amplitude/slow frequencies (indicated by large gaps between peaks) c. Stage 3 – SWS: Slow Wave Sleep – delta < 4Hz with increasing amplitude d. Stage 4 – now is considered as part of Stage 3 and is commonly referred to as “Slow Wave Sleep (SWS) 2. Rapid Eye Movement Sleep (REM Sleep) Electrical signals 1 Measuring positive and negative signals – measuring electricity coming from the brain or eye muscles Quiet wakefulness: Alpha 8-12 hz N1/N2:Theta 5-7 hz SWS: Delta >4 hz REM: Alpha/Theta 1. An EEG, EOG and EMG in quiet wakefulness (sitting relaxed with eyes closed – there is some blinking). Frequency is measured in hertz = cycles per second (how quickly going up and down). In restful wakefulness typically see alpha activity = going up and down 8‐12 times per second EOG: Left eye movement channel EOG: Right eye movement channel EMG: muscle activity channel EEG: C3-A2 = the positioned over the central region of brain (C) and 3 means is over left hemisphere: odd number = left side; even number = right side 30 seconds worth of time 2. Non‐REM sleep: Stage N1 – transition stage between wakefulness and sleep 2 EOG: Slow rolling eye movements EMG: Not much change in muscle activity EEG slowing down: gaps between peaks are getting wider: going up and down fewer times per second. Theta activity: frequency of 4-7 cycles per second or hertz 3. Non‐REM sleep: Stage N2 – transition stage between wakefulness and sleep (1st stage of true sleep) EOG: Few eye movements EMG: continuation of moderate to high levels of muscle activity EEG: Theta activity continues but now also see larger amplitude & slower frequencies – large gaps between peaks indicating a lower frequency EEG (individual entities are called “K complexes”: a hallmark of stage 2 Non-REM sleep) “K complexes” and “sleep spindles”: hallmarks of Stage 2 sleep 4. Non‐REM sleep: Slow Wave Sleep 3 Wider gaps; frequency decreasing to delta activity < 4htz and amplitude (the height from peak to peak) is increasing. Measuring the firing of neurons and the synaptic currents (very small: millionths of a volt). To generate higher amplitude activity (vertical axis is the voltage) need lots of neurons firing synchronously. Predominance of delta activity and why is known as slow wave sleep. Still moderate levels of muscle activity. Activity in the eye channel is EEG activity: because eyes are close to the brain, the nodes used to pick up eye activity also pick up brain activity. 5. REM sleep: the traces change quite dramatically: most active time for dreaming: thought to stop muscle activation which might result from having an active brain (skeletal paralysis): REM sleep behaviour disorder – in which muscle paralysis mechanism is either reduced or non-existent and people are more likely to act out what is happening in their dreamlike states (sleepwalking is a nonREM sleep disorder) - is more like quiet wakefulness. EOG: Rapid eye movements and periods of quiescence EMG: Virtually no muscle movement: skeletal muscle paralysis (except muscles for breathing and eye movements) EEG: Back to a lower amplitude, slightly higher frequency EEG – resembles quiet wakefullness Sleep across the night: alternate between different stages across the night (approx. 4 cycles) sleep cycles approx. 90 minutes long 4 REM sleep is the black bar. 1st half of the night have more & deeper SWS. 2nd half of the night have more REM sleep. Which is a reason more likely to remember dreams if wake later in night. Note the regular pattern of cycles Periodic awakenings are normal. A hypnogram showing the different stages or depths of sleep. Disrupted or fragmented sleep: As age tend to have more fragmented sleep. i.e., (i) wake up more (ii) lower levels of nonREM (SWS) Can also be caused by pain or chronic medical conditions Sleep Homeostasis: how sleep is regulated • Timing, quality, and depth of sleep 5 • Sleep is thought to be regulated homeostatically .  Regulatory processes are activated to ensure that appropriate levels of sleep occur, including “rebound effects” (sleep deeper on the night following a late night).  If sleep is reduced or disturbed negative consequences ensue, including: o o o Daytime sleepiness Inability to concentrate Potentially reduced cognitive functioning  The homeostatic process in sleep is reflected in the amount of SWS (deep non‐REM sleep): what does this mean????? (slide 13) • Generally, sleep occurs at a certain time over a 24-hour day. • A study of the body’s ability to control sleep timing.  A free running or isolation design.  Black bars show when asleep  In lab for over 50 days – no time cues/clocks/timed lights o 1st 20 days – sleep @ midnight and wake @ 8am (controlled when prompted to sleep) o Post 20 days no prompts: sleep time slowly drifts. o Tau for period of day was 24 hours but when average across the rest of time in lab the average length of day extended to 25 hours - is thought to be the natural day length. o The circadian rhythm – we have a number within the body – sleep/wake is just one of them: “it’s about a day” (ie about 245 hours). Individual variation in circadian rhythm: Smith et al 2009: Measure the internal body clock with several participants i.e., differences in circadian lengths (what a person’s preference is). The mean is just over 24 hours but is a distribution of that (some less; some more). Black bars are female participants. A constant routine protocol (previous was free reign): both were time isolation studies Smith MR, Burgess HJ, Fogg LF, Eastman CI (2009) Racial Differences in the Human Endogenous Circadian Period. PLoSONE 4(6): e6014. • How to synchronise length of circadian rhythm with 24-hour clock? 6  time givers – “zeitgebers”: the strongest of which is light (colours at blue end of spectrum seem to have more influence over circadian timing). These studies led to the development by Alexander Borbely of the two‐process (or two‐factor) model of sleep regulation (late 1970s; early 80’s): Borbely’s two‐factor model of sleep regulation: 1. Circadian oscillator: the internal body clock. 2. Homeostatic sleep propensity component. Sleep propensity/drive increases as a function of prior wakefulness and decreases as a function of sleep. So that the longer stay awake the more tired you get, will then sleep for a length of time depending upon how long were awake for previously and so the need/drive/propensity to sleep (or sleep pressure) dissipates across the sleep period. Does it make a difference when sleep occurs with respect to the circadian oscillator (i.e., the internal body clock)? YES! Circadian rhythm can be seen in a number of different variables in the body – hormones; a stronger indicator is core body temperature. Have highest core body temperature in late afternoon/early evening and lowest in the wee hours of morning (why feel cold when wake up in the small hours). Optimal time to fall asleep is on the descending phase of body temperature and likely to have the most consolidated sleep. If try to sleep outside these times - have desynchrony btw internal body clock and when sleeping Two Forms of Desynchrony Desynchronisation between the internal body clock and when are sleeping. 1. Internal Phase Desynchrony (shift work)  When the appropriate phase relationship between the circadian oscillator and the sleep‐wake cycle is not maintained.  Difficulty getting to sleep.  More disrupted sleep (second wind – 5-6 am) 2. External Phase Desynchrony (jet lag) 7  When the circadian oscillator does not have the appropriate relationship with external zeitgebers (most prominent of which is light)  Before travelling across time zones – try to set the sleep wake cycle and eating cycle to be closer to the destination zone and when arrive, be active and eat when fits the destination time – will synchronise more quickly. What is the Function of Sleep? Likely to be a combination of • Protection (from predators)? • Energy conservation? • Restoration?  Body  Brain Neuronal Connectivity and Sleep One common theory as to the function of sleep is that it serves to maintain, consolidate, or repair synapses and the neuronal circuits within which they function. E.g., Learn things during days – investigating the environment so get strengthening of synapses – then argued sleep serves to reduce the activity of neural circuits that are not used as much. Does this reorganisation of neural connectivity hypothesis mean that the function of sleep is: 1. To facilitate general maintenance of all synaptic connections across the Central Nervous System (a general tidy-up of a messy filing cabinet)? OR 2. Is this reorganisation regional and use dependent? That is, is it directed at those synapses formed or modified during wakefulness. E.g., if practice something during the day, do you tend to get more activity in those neural circuits during sleep to consolidate them? An Amalgam of Concepts: 1. Sleep likely to facilitate neuronal connectivity. 2. Sleep is a homeostatic process (is use dependent) reflected in and measured by the amount, duration, and intensity of SWS (deep nonREP sleep). 3. Therefore, is argued that the amount of SWS reflects the synaptic repair/maintenance processes (need to generate the high amplitude; low frequency EEG, or delta activity, that see in SWS – i.e., need lots of well-connected neurons firing at the same time) 8 4. If 1‐3 hold true, then changes in SWS should be specific to the area of the brain that’s used for a particular task Vyazovskiy, Borbely and Tobler (2000). Journal of Sleep Research, 9, 367‐371. • • • Unilateral sensory stimulation during wakefulness in rats by cutting whiskers on rats one side to reduce sensory input to contralateral cortex. Rats then spent 6 hours in an enriched (novel) environment to explore. Measured cortical activity (EEG) in the subsequent sleep period and compared amount of SWS in the two hemispheres. Found significantly elevated lower frequency (SWS) in the contralateral cortex where had whiskers – only seen in the <5Hz frequencies supporting that the intensity of sleep, and particularly of SWS, is use dependent and is maximal over areas of the brain used for the particular task. Similar studies in humans have found similar results. The homeostatic model implies that short sleep duration is bad, while long sleep duration is good, although the benefits of longer sleep duration diminish exponentially. So sleep pressure dissipates quite rapidly across the sleep period. Kripke et al., 2001 A famous prospective cancer prediction study : • One question was “how many hours do you sleep on average a night” • Collected data in 1982 and looked at mortality data in 1988. Just over 1.1 million participants • Research question: does the amount a person reports sleeping predict the likelihood of death in the follow-up period after controlling for SES, cardiovascular disease etc? • Results: association between sleep duration and mortality (hazard ratio) and % of people obtaining different sleep durations (% women and men) Females Males Hours of sleep and % of individuals reporting that many hours. The hazard ratio: the likelihood of dying over the study period For both women and men – the mean # of hours of sleeping: 7-8 hours. Increased risk of mortality for short AND long sleepers compared to average sleepers (compare homeostatic model which says more sleep is always good). Effects probably quite small but found statistical significance due to very large size of sample. What is the optimal Sleep Duration? • • • The reported population norm of 8 hours? Sleep duration associated with the lowest mortality? Sleep duration associated with optimal daytime functioning? 9 • • Is there any flexibility in sleep duration and still optimize and individual’s functioning? How important are individual differences and potentially genetic factors? Sleep is actively controlled by brain structures: It is not a passive state (it is not the absence of being awake) but is actively controlled by various structures within the brain. Von Economo (neurologist in early 1900s) • Post-mortem studies: encephalitis epidemic in 1920’s/30’s • Prolonged sleepiness (hypersomnia) prior to death was found to be related to lesions of the posterior hypothalamus and rostral midbrain. • Insomnia was related to lesions of the pre‐optic area and the basal forebrain. • Based on this he predicted that the region of the hypothalamus near to the optic chiasm contains sleep promoting neurones, whereas the posterior hypothalamus contains neurones that promote wakefulness. • Areas that produce wakefulness: use neurotransmitters which are largely stimulatory (don’t need to remember these 1:23 of recording). o BF: Basal Forebrain: cholinergic neurons o TMN: histaminergic neurons (if take antihistamines, get drowsy); orexin/hypocretin neurons (wakefulness promoting neurons) o Raphé: serotonin o LDT/PPT cholinergic (where the REM/nonREM switch is thought is to be located). Change in cholinergic activity in the LDT/PPT indicates switch from nonREM to REM period) o LC locus coeruleus: noradrenergic All are active to varying degrees during wakefulness and are reduced when asleep with exception of increased cholinergic activity in the mid brain when go into REM sleep – EEG activity in REM is more like wakefulness than SWS. 10 Behavioural studies – Sterman and Clemente, 1962: stimulated various parts of cat brains. Found that bilateral stimulation of the basal forebrain resulted in a behavioural response of a rapid transition from waking behaviour (alertness to engagement) to sleep or withdrawal from the environment . Sleep Characteristics are Genetically Transmitted Measuring sleep in Drosophila (fruit fly) (Huber et al., Sleep, 2004, 27, 628-39): behavioural measure of sleep: characteristics of sleep across organisms: • • • • • reduced activity higher threshold of alertness: “higher arousal threshold” poke harder to wake up measure movement/activity with light gate thermal element could provide a stimulus: measure arousal threshold could produce sleep deprivation by vibrating the tray. 11 Found behavioural immobility is associated with increased arousal thresholds - measure how quickly the flies move post stimulus. Y axis: activity/arousal threshold X axis: duration of immobility prior to stimulus If only asleep for a short period – tended to respond quickly If asleep for longer they tended to not response to the low-level stimulus Looked at the genetics of the Drosophila (commonly used in genetic experiments as have rapid reproductory lifestyles and short lifespans) Distribution of sleep duration over different lines and the diurnal pattern for “mini sleep” flies and “Wild Types” Panel a: distribution of the amount of sleep several flies getting in a given 24 hour period. Males tending to sleep longer. Panel b: Y inactivity per 30 minutes: X axis – time. Mini sleepers (“mns”) not getting as much sleep compared to controls (the “wild type”) . Sex difference: showing a genetic code mapped onto the X chromosome and was recessive. Females with 2 genes with genetic variation for mini sleep they expressed it. Males only expressed it if had the gene in its single X chromosome. One way can show that can be a genetic influence in individual differences in sleep duration. Genes have been associated with other aspects of circadian rhythm etc. 12 Metabolic Aspects of Sleep Several things change dramatically between wakefulness and sleep, and one is metabolism (i.e., how much energy we consume or use during wakefulness and sleep) Kreider & Iampietro, 1959 Y axis: 3 different measures: Rectal temperature: core body temp Skin temperature Oxygen consumption: metabolic rate X axis: time in bed – zero hours being time fell asleep. Measured over 8 hours and 3 different conditions of ambient temperature: 25.5C, 15C and minus 32C. Expected difference depending on ambient difference – not as obvious in metabolic rate (oxygen consumption). In first hour get: • • a dramatic decrease in core body temperature and metabolic rate and a slight increase in peripheral (skin) temperature.  These are thought to be effect of falling asleep. Then after 1st hour see a slower decline and then increase.  this is thought to be the circadian effect. The study offers one way to tease out what is an effect of asleep (i.e., the act of being asleep rather than awake) vs what is more influenced by the internal body clock (circadian effect) . Lose ability to thermoregulate during REM sleep – don’t sweat or shiver – in extreme conditions, have less REM sleep to conserve body temperature. 13 Cardiovascular Activity and Sleep Also changes markedly in sleep. Trinder et al., 2001 Dotted vertical line = sleep onset – drastic drop in blood pressure (also seen in heart rate) - the sleep effect. Then a gradual increase which reflects the circadian effect. Fraser et al., 1989 Same thing seen in oxygen consumption measured over 3 conditions: Condition 1: go to sleep at normal bedtime Condition 2: held awake and sleep 2 hours after normal bedtime Condition 3: go to sleep 6 hours after normal bedtime. See a drastic decline at point fall asleep but also a gradual decline in conditions 2 and 3 across the night when normally would be asleep which is thought to reflect the circadian decline over the night. A lot of these variables are influenced by both:  the state a person is in i.e., sleep or wakefulness and  circadian influence i.e., where they are on their own internal body clock 14 The relationship between sleep and metabolic factors is reciprocal: Krauchi et al., 2000 (don’t need to know the detail of this) Skin temperature: difference between distal (finger/toe) and proximal (neck/chest)skin temperature: this is the biggest indicator of how rapidly someone will fall asleep. Salivary melatonin: a hormone with a strong circadian rhythm Sleepiness: need to measure when awake Core body temperature including rate of change All follow slightly different patterns but can see they are relatively synchronis. 15 RECORDING CUTS OUT HERE: REST OF LECTURE NOT EXAMINABLE Does sleep play a role in the consolidation of memories? Generally, this is understood to mean facilitation of synaptic plasticity. Huber et al. (2004). Nature, 430, 78‐81. • Subjects were required to engage in a motor leaning task just before going to sleep • One session with a hard task and one with an easy task • The task is known to activate particular cortical areas (right parietal, Brodmann areas 40 and 7) • Subjects then sleep and 256 channels of EEG recordings were collected for the first 2 hours of sleep • Performance was then assessed in the morning Motor Learning Task a. Average Power Spectra (1-4 Hz) 16 b. Difference in Power Spectra (1-4 Hz) a. Performance enhanced by sleep b. Performance increase correlated with the SWA increase 17 18