Sleep Flashcards
What is sleep?
Period of reduced activity and decreased responsiveness to external stimuli.
• Reversible loss of consciousness and behavioral control (distinguishes sleep from other states of reduced consciousness, such as hibernation and coma
Describe sleep as restorative
350 BC: Aristotle argues that consciousness resides in the heart and that the onset of sleep is the result of warm vapors that rise from the stomach during digestion
1650: Thomas Willis localizes consciousness to the brain.
1890s: Histological theory of sleep (Duval) – retraction and expansion of dendritic extensions from sleep to wake states.
1890s: Vasomotor theory of sleep (Howell) – reduced blood flow to the brain during sleep (cerebral anaemia)
How is sleep anxiety reducing, replenishing, memory enhancing?
SLEEP AS ANXIETY REDUCING
1899 Freud argues that dreams reflect unconscious wishes and sexual or aggressive fantasies that are repressed during waking states
SLEEP AS REPLENISHING
1916: Constantin von Economo - the hypothalamus generates sleep/wake states (lesion studies); sleep allows for clearance of toxins that accumulate in the brain during the waking state.
SLEEP AS MEMORY ENHANCING
1924: Jenkins and Dallenbach show positive effects of sleep on memory, initiating a century of debate on the role of sleep in memory consolidation
Who was Hans Berger?
1929: Hans Berger introduces the encephalogram (EEG) and the study of electrographic changes between sleeping and waking states
What are the methods for studying sleep?
EEG with additional electrodes for heart rate, eye and body movements, respiration, etc.
PET (Positron emission tomography); changes in cerebral blood flow (CBF), glucose metabolism
fMRI → changes in blood oxygen level dependent response (BOLD)
Magnetoencephalography (MEG) = magnetic signals generated by neural
activity
MEG localizes sources of neural activity better than EEG
MEG cannot provide detailed images like fMRI does
Summarize methods of studying sleep
Polysomnogram (PSG) Sleep Study
- Electroencephalogram
- Electrooculogram
- Electromyogram
- Electrocardiogram
- Pulse oximetry
What is electroencephalogram?
Recordings of electrical potentials from different electrodes placed on the scalp against a reference electrode
How does an EEG work?
EEG records very small electrical fields generated by synaptic currents in cortical pyramidal cells
Each square millimeter of cortex has more than 100,000 neurons.
Signals are low in amplitude so a differential amplifier is used.
Thousands of neurons must be summed to create a discernible EEG signal.
Describe EEG Synchrony
Desynchronized
Cortical activity causes
low (voltage) amplitude EEG waves; normal awake brain
Synchronized
Cortical activity causes
high (voltage) amplitude EEG waves; sleeping brain
What are EEG signal characteristics?
Recordings are characterized by their amplitude (voltage) and their frequency (Hz)
What are the stages of sleep EEG rhythms?
EEG brain rhythms relevant for sleep staging
Beta- (12-40Hz)
Alpha (9-12 Hz)
Theta (4-8) Hz)
Delta (0-4Hz)
What are the EEG rhythms during sleep?
Rapid Eye-Movement Sleep (REM)
Stages N1 and N2 are considered “lighter” stages of sleep
Stages 3 and 4 also referred to as slow-wave sleep (SWS); now these have been combined as stage N3
What are the basics of Sleep EEGs?
An electroencephalogram (EEG) is a set of recordings of electrical potentials from different electrodes placed on the scalp against a reference electrode. For each electrode, the recording reflects the sum of electrical activities underneath.
The recordings are characterized by their amplitude and their frequency (measured in second-1 or Hz). Low amplitudes are due to low levels of synchronization and do not necessarily reflect absence of brain activity. Low synchronization levels result from cancellation of depolarizations of some neurons by hyperpolarizations of other neurons. When depolarizing and hyperpolarizing events are synchronized, higher amplitudes are measured in the recordings.
A brief introduction into measuring brain activity with an EEG is given in your Siegel and Sapru text Chapter 24: THE LIMBIC SYSTEM: Measurement of Brain Activity: The Electroencephalogram.
Different stages of sleep are associated with different frequencies and amplitudes and an EEG can help analyze which sleep stage a person is going through, as well as record duration of each of the sleep phases. In addition, short phases of altered activities, such as sleep spindles and K-complexes, occur during certain stages of sleep.
What is a hypnogram?
REM sleep becomes more prominent towards morning
Normal sleep cycle:
~90 minute cycles
~7 hours per night
~80% NREM sleep Highly ordered structure
What is sleep. Pressure?
- Homeostatic process that keeps track of how long we have been awake.
- The longer we are awake, the greater the build-up of sleep pressure, possibly reflected by adenosine levels.
- Sleep pressure interacts with the circadian sleep rhythm.
What are the arousal vs sleep systems?
Arousal systems (cholinergic and monoaminergic pathways) and sleep-promoting systems (GABAergic pathways) are mutually inhibited by turning off each other’s circuitry.
The circuitry that governs sleep/wake cycling is analogous to a flip-flop electrical switch with either an ON state or OFF state.
This switch is controlled by GABA containing neurons in the ventrolateral preoptic region (VLPO) of the anterior hypothalamus that turn off arousal systems in the Ascending Reticular Activating System (ARAS)
Describe the neuroanatomy of sleep
What does the ascending reticular activating system have to do with sleep?
A big leap in understanding sleep was the discovery of an endogenous system that normally keeps cortex active and aroused. This endogenous system was classified as ‘ascending reticular activating system’ (ARAS).
The important components of the ARAS are
1. Cholinergic systems of PP (Pedunculopontine)/LD (Laterodorsal) Tegmental
nucleus that project to the thalamus and other areas.
2. Monoaminergic systems that project directly to the cortex and include
3. Serotonergic projections from raphe nuclei,
4. Noradrenergic projections from locus coeruleus,
5. Dopaminergic projections from ventral tegmental area
6. Histaminergicprojectionsfromtuberomamillarynuclei.
7. Cholinergic systems of the basal forebrain also join the monoaminergic
projections to the cortex
8. FacilitatingandenhancingthemonoaminergicprojectionsaretheOrexinergic
neurons from the lateral hypothalamus
Describe sleep circuitry
Wakefulness
Ascending Reticular Activating System (ARAS): • PPT: pedunculopontine nuclei • LDT: laterodorsal tegmental nuclei • RN: raphe nuclei • LC: locus coeruleus • VT: ventral tegmentum
Hypothalamus
VT
• LH: lateral hypothalamus
• TMN: tuberomammillary bodies PPT Basal Forebrain (BF)
• septal nuclei, nucleus basalis
Sleep
Hypothalamus
•VLPO: ventrolateral preoptic region (GABA, galanin neurons)
What are the reticular Activating System?
Cholinergic systems
• Project to the thalamus and cerebral cortex
• PPT=pedunculopontine
• LDT=laterodorsal tegmentum
Monoaminergic systems Project directly to the cortex RN = raphe nuclei (serotonergic projections) LC = locus coeruleus (Dopaminergic projections) TMN = tuberomammillary nuclei (histaminergic projections)
Describe RAS cholinergic output
The cholinergic system (ACH) promotes thalamic and cortical activity during the wake period
ACH projections to the thalamus influence the firing patterns of sensory relay neurons.
What is Reduced sensory responsiveness during sleep?
The thalamus contains sensory relay stations, which are in “transmission mode” during waking state but go into “burst mode” during slow wave sleep (SWS):
• LGN-vision, MGN-audition, VPL-somatosensor
What is the sleep/wake switch ?
Mutual VLPO/MA inhibition promotes an absolute behavioral state (sleep or wakefulness) with little room for any transitory state.
Animals with VLPO lesions show 50-60% reduction in sleep time but also wake up more frequently.
Aging is associated with reduction in VLPO neurons and less stable sleep/wake circuitry
What’s the significance of Suprachiasmatic nucleus?
The SCN has minimal projections to the VLPO
How do light cues influence the sleep/wake switch?
SCN strongly innervates the subparaventricular zone (SPZ) of the hypothalamus and the dorsomedial hypothalamic nuclei (DMH).
DMH integrates feeding, temperature, and light cues from SPZ and SCN.
DMH has GABAergic projections to the VLPO and excitatory projections to the LH.
Thus, the DMH is an important conduit for light and other environmental cues to influence the sleep/wake switch
What is NREM?
Depressed ARAS pathways to basal forebrain (VLPO/GABA)
→onset of NREM sleep WAKE-OFF/REM-OFF
What is REM?
Transient cholinergic cell activation during sleep
→onset of REM sleep WAKE-OFF/REM-ON
Compare REM to NREM
Compared to NREM, REM involves increased blood flow in:
– Pons, midbrain, basal ganglia, thalamus, basal forebrain
– Paralimbic regions: anterior insula, anterior cingulate, mesial temporal
– Association cortices: visual, auditory
Compared to REM, the awake brain has increased rCBF in:
– Heteromodalassociationcortices
– Dorsolateral prefrontal cortex
Paralimbic activity higher in REM than awake brain
Which ARAS systems are active during the different sleep stages?
As we fall asleep from being awake, we enter into 1st stage of NREM sleep (stage 1). NREM sleep is differentiated into three stages.
Through these three stages, the ARAS is actively inhibited by the projections from GABAergic Ventro-Lateral Preoptic Nuclei (VLPO). Both the cholinergic and monoaminergic systems are slowed down in NREM sleep. The very high ratio of GABA to ACh during NREM sleep is highly suggestive of GABAergic neurons’ active role in sleep induction and maintenance, in particular of NREM sleep.
During REM sleep, there is active inhibition of muscle tone (of the body) and sensory afferents. This sleep is also frequently referred to as ‘dreaming sleep’ or ‘paradoxical sleep.
The paradox being, though in sleep, the brain is very active, akin to that of an awake one. Select cholinergic projections from LDT and PPT (Pedunculopontine and lateral dorsal tegmental) nucleus to the pontine reticular formation are released from inhibition and the activation of these circuits become the basis of REM sleep. REM sleep is also distinct in that LDT/PPT neurons mediate inhibition of monoaminergic neurons.
How is REM sleep activated?
- Active inhibition of motor system, except for respiratory and ocular muscles
- “An awake brain in a paralyzed body”
- Ventromedial medulla neurons inhibit spinal motoneurons during REM-associated motor atonia (via spinal cord interneurons)
What is sleep paralysis?
Sleep paralysis can persist into the waking state
- Can be accompanied by hypnopompic hallucinations
- Many cultures have a word for this: alpdrücken (German); kanashibari (Japanese); bakhtak (Persian)
Describe the wake stage
ECG: low voltage, high frequency; desynchronized
Sensation: vivid, externally generated
Muscle tone: continuous, voluntary movements
Eye movement: often
Describe Stages N1-N3
EEG: high voltage, low frequency; synchronized
Sensation: dull, absent
Muscle tone: occasional, involuntary movements
Eye movements: rare
Describe REM sleep readings
EEG: low voltage, high frequency; desynchronized
Sensation: vivid, internally generated
Muscle Tone: m uscle paralysis, lower motor neurons inhibited
Eye movements: often
Describe age related changes of sleep
Total duration of sleep time per day.
• Babies sleep for 16 hours per day.
• Elderly spend only 6 hours per day sleeping
REM sleep changes.
• Babies may spend 50% of
their sleep time in REM sleep
• Adults between 20 and 50 years of age may spend only 20% of their total sleep time in REM sleep.
Reduction of galanin containing neurons in the VLPO is associated with increased sleep fragmentation in the elderly
