2 - Studying Sleep and Circadian Rhythms Flashcards
In 1938, a couple people went into Mammoth cave (total darkness and constant temperature) for 30 days.
First reference of daily rhythms are in the ____
Bible, song about life during night/day
Carl Linnaeus describe sleep movements in the mimosa plant, what was the significance of this?
First to describe activity pattern governed by a biological rhythm
Reported that he took the sensitive plants and put them in a darkened closet and left them there for many days. Peaked in periodically to see position of leafs. Concluded that plant continued to have sleep movements regardless of lack of sunlight, said that it could sense the sun (dead wrong)
Experiment repeated with constant light, movements remained.
Eventually discovered that this was due to an internal biological clock.
Kurt Richter invented running wheel to measure rats activity without disturbing them. What was his findings from this (1920s)?
That rat’s period activity fluctuated. If blinded, their period was not 24 hours. Same with drosophila.
Intensity of lighting makes what different to biological rhythms?
Produces different rhythm periods (longer/shorter)
What are circadian rhythms?
Rhythms that are generated near a 24 hour period (though not exactly). A dian rhythm is exactly 24 hours.
When a rhythms is being expressed in constant environmental conditions, it is called a?
Free running rhythm
A period slanting leftwards on a 24 hour time scale is less than, or greater than 24 hours?
Less than
Leftward slant demonstrates the animal waking up earlier and earlier
Humans have a free running period at about ___?
24.1-24.3 hours
Why is the free running period important?
Internally generated circadian rhythm is synchronized to light/dark cycle (entrained)
What is entrainment?
An organism with an internal clock by synchronized to an external cycle (eg. light and dark)
How do we know we are observing entrainment and not a 24 hour free running period?
Leaving everything constant except for one variable, shifting to a new external cycle (phase shift). If the animal adapts to a new light/dark cycle, that is entrainment.
What is a zeitgeber?
An entraining agent (a ‘time giver’)
What is the limit of entrainment?
Animals can only be entrained to cycles close to their biological cycle
Species differ by how much they can deviate from their biological cycle (humans very conservative and resist change - NASA 25 hr experiment failure)
A brief light pulse administered during a free run has what consequence?
A permanent phase shift to synchronize to the new period indicated by the light (phase delay or phase advance)
Your clock is reset every day by what two factors?
Internal clock and external cues cause unique entrainment for each individual
Organisms with short periods (short oscillator) have what 24 hour position?
Early phase (leading) relative to external cycle
Organisms with long periods (long oscillator) have what 24 hour position?
Late phase (lagging) relative to external cycle
How do circadian rhythm phase lead and phase lag change from childhood to adulthood?
Shift from childhood to adulthood of late phase (lagging - late riser - long periods) to early phase (leading - early riser - short periods)
EEGs need a reference electrode, where are these usually placed?
Behind the ear
What does submental mean?
Under the chin
An EEG site starting with C denotes?
Central central
What is a polysomnogram (PSG)
Set of measures that gives you a comprehensive physiological overview of a sleeping person.
What are the 6 components of a PSG?
- brain (EEG),
- Eye movements (EOG),
- Muscle activity or skeletal muscle activation (EMG) and
- Heart rhythm (ECG) during sleep
- Airflow
- Leg movement
When are intracortical recordings of humans made?
Seizure patients undergoing surgery. Electrodes are implanted and cortical activity monitored for a few days to detect source of seizures.
What is the 10/20 system for EEG montages?
Each electrode positions are done with respect to distance percentages from anatomical features of the skull. Distances between left and right and nasion (eye socket) and inion (bump on back of head)
Why are action potentials difficult to detect by EEG?
Very rapid
What are EEGs mostly picking up on?
The summation of all the excitatory and inhibitory postsynaptic potentials under the electrode
what layer of the cortex are EEGs mostly measuring from?
The densely soma-populated fifth layer of the cortex is the main source of electrical activity.
If neurons are desynchronized from each other and you record from many neurons that perform individual tasks where they are stimulated by a specific sensory input. What type of activity are you recording with EEG? What is this called?
You wind up with an EEG recording very close to zero (very short peaks oscillating around zero line) because different neurons are getting excited and inhibited and some are inactive.
Called a desynchronized cortex
Where does the cortex receive its synchronizing signals from?
The thalamus
What is the function of a synchronized cortex?
To prevent the processing of sensory information. Seen during sleep (esp gamma waves)
What is Fourier analysis?
Taking a waveform and reducing it to simple sine waves. Any arbitrary waveform can be analysed as a series of pure sine waves added together.
The accurate weighting (aka power, frequency) of each simple sine is added to achieve the original waveform
Fourier analysis also tells you what the fundamental signal frequency is (power strectrum)
What frequency is dominant for wakefulness?
Beta (over 13 Hz)
What is stage 1 sleep frequency?
Alpha frequency (8-13 Hz)
Relaxed wakefulness achieved in meditation
What is the sigma frequency range?
13-30 Hz
What is the gamma frequency range?
Over 30 Hz
What is the theta frequency range?
4-8 Hz
What is the delta frequency range?
1-4 Hz
What is a delta wave?
A wave with at least 75 mV (up to 150 mV) of amplitude and falls within the delta range (1-4 Hz)
Slow wave sleep is defined by?
Delta waves
Why is the EOG critical for a PSG (polysomnogram)?
REM sleep is almost indistinguishable from stage 1 and wakefulness. Slow rolling eye movements stop in stage 1, rapid eye movements start during REM sleep, and they don’t occur in any other stage in sleep.
Why is the EMG critical for a PSG?
Muscle tone is slightly maintained throughout sleep, until REM sleep when it is lost. (usually measured on chin)
What stage of sleep is the longest?
Stage 2 (50% of night)
It’s also the most ‘unremarkable’
What are K complexes?
Occurs in stage 2 sleep. Errant delta wave (or ‘slow wave’) that appears transiently.
What is a good way to evoke a K complex? What often accompanies this?
To create a sound in the environment. A sleep spindle often accompanies the K complex.
What is the appearance of a sleep spindle on EEG?
Horizontal spindle shape
Low amplitude to high amplitude and back to low
How many microvolts is a delta wave? K complex?
Delta wave: 75-140 microvolts (1-4 Hz)
K complex: over 140 microvolts
In what stage of sleep do delta waves begin?
Stage 3
What is nREM stage 3 sleep?
Slow wave sleep
used to be called stage 3 and stage 4
How many Hz and microvolts are slow waves?
under 1 Hz
Over 140 microvolts
Why are slow waves ignored and lumped into delta range during EEG recording of sleep?
Slow waves are not properly recordable
What does slow wave sleep refer to?
Stage 3 nREM sleep
Is slow wave sleep a ‘deeper’ sleep than other stages?
Only using the criterium that it is harder to wake them out of sleep in stage 3 nREM sleep and the sleeper will have sleep inertia
What is sleep inertia?
The period of time after awakening from sleep where you are returning to normal function and alertness (reduced cognitive and physical performance)
May not recognize where, who, what or why
Lasts seconds to minutes
What is the hallmark of the onset of REM sleep?
The sudden loss of all muscle tone (atonia - sleep paralysis)
What stage precedes REM sleep?
nREM stage 2 sleep
What does the PSG of REM sleep look like?
- Mixed frequencies on EEG
- Low voltage (amplitude) on EEG
- Nearly flat EMG
- Rapid eye movement in same direction (conjugate) for both eyes (on EOG)
- PGO (pons-geniculate-occipital) spikes
What are PGO spikes
Spikes in synch with rapid eye movements in REM sleep, moving from the pons (sleep paralysis generation) to the lateral geniculate and then to the occipital lobe of the cortex
Is there any movement during REM sleep?
Only in peripheral muscles (eg. fingers, toes, ears in dogs and cats etc.)
In nREM stage 3 sleep, are you parasympathetically or sympathetically dominant?
Parasympathetic
In REM sleep, are you parasympathetically or sympathetically dominant?
Sympathetic
- Erratic heart beat
- Penile erection, clitoral engorgement
- Increased breathing etc.
Autonomic regulation seemingly
‘shut off’
Is REM sleep ‘deep’
Yes, very difficult to awaken someone from it
What is phasic REM sleep?
Phasic REM sleep is the portion of REM sleep during which there are phasic bursts of rapid eye movements, which may be associated with brief bursts of EMG activity (sometimes called twitching) and/or sudden increases in sympathetic activity.
What is tonic REM sleep?
Tonic REM sleep is the portion of REM sleep that exists between the phasic bursts
What is the negative implication of sleep labs?
They are extremely sound insulated, and completely dark. Not how people usually sleep. Also putting someone in a strange environment
The advantage is that you can control everything besides the sleeper’s sleep.
What is the ‘first night effect’
The first night sleeping in a novel environment usually produces poor sleep. This is why many sleep study participants sleep in the sleep lab once with no measurements and then again for the experiment.
Your brain filters out what you’re used to
The clinical categorization of sleep stages is in some parts arbitrary, why?
For an internationally recognized definition
What is actigraphy?
Taking measurements of acceleration (with accelerometer) of human activity (including sleep/wakefulness)
What is a problem with actigraphy for measuring sleep?
People move before falling asleep and waking up from sleep
Hard to detect when you actually sleep by movement alone
When is actigraphy useful in sleep studies?
For prestudies, to make sure people don’t lie or give false information before they come into the sleep lab.
Also decent for daily activities. Trivial cost (PSG is expensive)
How can GFP (green fluorescent protein) be used as a marker of circadian rhythms?
Link expression to activation of the period gene
Similar to using luciferase enzyme, which fluoresces in response to luciferin
How do you prepare a setting to study circadian rhythms?
- Completely isolated from any external environmental cycle cue (zeitgebers) (temporal isolation)
- Temperature, humidity etc.
- Isolate from random light, noise or any other extraneous variables
What are masking effects when studying circadian rhythms?
External event that causes an animal to behave other than how they should behave in circadian cycle that they’re in (eg. waking them up when they should be asleep)
Stimuli different from what entrains their system
What are negative masking effects?
Eg. putting a songbird during day into darkness
Withdrawing behaviours that it should be showing
How can light and dark (zeitgebers) have a masking effect?
Eg. plunging an animal with a circadian cycle into continuous dark, they will usually continue to generate ‘free-running’ rhythms, however,
if the animal becomes arrhythmic, then you conclude that the animal has no internal clock (and therefore light/dark is a masking effect in this case)
Is introducing a light/dark cycle to a free running organism masking?
Yes, as long as the free running rhythm after the masking matches with the free running pattern before the masking.
During the masking, the organism could align to light/dark, but this is not entrainment unless the free running starts from the point predicted by entrainment (see slides for clarification)
Who was Aschoff?
1950s German physiologist that used underground bunkers as zeitgeber-free environments. Found that people living in these environments immediately lost track of time and began living in much longer periods (awake for 30h and sleep for 12 - unaware of this change). Physiological measurements however, were still tied to 24h. This was called spontaneous internal desynchronization.
What is Spontaneous internal desynchronization?
Discovered by Aschoff. When people left in an environment without zeitgebers, they adapt to different periods.
What is internal masking?
Masking/skewing by circadian rhythms, by things you do yourself
Eg. the thermogenic effect of eating too much food or exercising.
What is the ‘constant routine?’
A technique of circadian rhythm study where participants follow a rigid routine. This is to prevent internal masking.
- Same meals at rigid times, awake, EEG monitored, no exercise or activity whatsoever.
What did Czeisler show about human circadian rhythms?
That out clock runs at about 24.1 hours (rather than about 25, which was previously thought)
What is the forced internal desynchronization approach?
Force people to do things at different times than they normally would in a constant routine. Participants are told when to sleep and when to wake. They are then put on a 28 hour day or 21 hour day etc, where they must be asleep for 1/3 of that time. Sleep/wake cycle is desynchronized beyond the limit of entrainment.
What is the purpose of forced internal desynchronization?
Can separate entrained internal clock from circadian rhythms? Can separate factors producing REM sleep/slow wave sleep.
What is Process S? What causes its level to increase and decrease?
The hypothetical homeostatic regulation for the accumulation and dissipation of the need for slow wave activity.
Increased ‘sleep stuff’ (either chemical substance or neural process) builds up until it is dissipated by periods of sleep that include SWA
Describe some of the results of Kim et al. (2007) that are not consistent with homeostatic regulation of SWA.
- During rat sleep deprivation on wheels, rats did not compensate for lost SWS in four hour sleep opportunities, relative to baseline.
- Rats lost a great deal of both sleep and delta power cumulatively over five days of sleep restriction
- May be due to HPA allostasis
Kim et al. (2007), Leemburg et al. (2010) and Deurveilher et al. (2012) found different results with respect to sleep parameter changes after chronic sleep loss. Describe these differences and discuss how methodological differences might contribute to them.
Kim: Increased REM, decreased nREM (odd), allostatic regulation by HPA was explanation (eeg may not have been adequate to fully observe homeostatic response)
Leemburg: Disk over water, Preservation of SWA homeostasis throughout study (good)
Deurveilher: Natural polyphasic cycle, increase in nREM and REm with increased delta power, increased sleep drive and preservation of homeostatic sleep regulation. More natural circadian rhythms observed. Not complete compensation for REM, nREM or SWA during recovery days, suggesting allostatic adaptations also occured.
What is the evidence from animal and human studies with respect to whether REM sleep is homeostatically regulated after acute sleep loss?
When people are selectively deprived of REM, robust increase in REM observed during an immediately following recovery sleep interval.
What species differences have been demonstrated in how REM sleep responds to chronic sleep loss?
Humans show REM rebound only after SWA has been made up.
Rats may show REM rebound immediately
Which sleep characteristics are shared by the platypus and the ostrich? What do these similarities suggest with respect to the evolution of REM sleep among mammals and birds?
- Atonia and rapid eye movement during cortical slow waves (brainstem REM sleep)
- These observations suggest that brainstem REM sleep, accompanied by cortical desynchronization –the form of REM sleep seen in most modern birds and mammals, emerged only gradually in the later evolution of these groups.
- One interpretation would be that primitive higher vertebrates originally showed slow cortical waves continuously during their form of NREM sleep. Bouts of ‘brainstem REM sleep’ evolved (but why?) and began to occur periodically during slow-wave sleep, as seen in the platypus and ostrich today. Modern REM sleep, with its paradoxical combination of ‘brainstem REM sleep’ and cortical desynchronization replacing the original slow waves, may reflect a subsequent evolutionary change in the cortex that made it maladaptive to maintain lengthy periods of synchronized slow waves during sleep. If this idea is correct, then the form of REM sleep expressed in most birds and mammals would have evolved because of these unidentified negative consequences of sustained NREM sleep.
