Brain Rhythms and Sleep

Question 1

What is the electroencephalogram?

Answer 1

• Measurement of electrical activity of the cerebral cortex
• Electrodes are taped to scalp in standardized positions and amplifiers are used to boost the electrical signals
• Records voltage changes between pairs of electrodes (e.g., anterior / posterior, lateral / medial)

Question 2

What type of cells of the cortex generate activity that is detected by electrodes?

Answer 2

• Pyramidal cells
• Fire in mass, which generates enough current to be detected
• Requires activation of many thousands of neurons together in the cerebral cortex (low spatial resolution)

Question 3

What element of the EEG signal depends on synchronous activation of cortical neurons?

Answer 3

• The amplitude of the EEG signal
• When multiple cells fire in synchrony, there is a standardized change in electrical activity
• When cells don’t fire in synchrony, sum of EEG activity is flat

Question 4

List the 6 EEG rhythms and the behavioural states associated with each.

Answer 4

1. Delta: slow (less than 4 Hz) – deep sleep
2. Theta: 4-7 Hz – sleeping and waking states (relaxing or light sleep)
3. Alpha: 8-13 Hz, large and extremely regular waves that occur mostly over occipital cortex – drowsy, waking states (e.g., lying down and closing eyes while still awake)
4. Mu: 4-7 Hz, occur mostly over somatosensory and motor cortices – physical resting state
5. Beta: 15-30 Hz – fast activity, normal waking consciousness
6. Gamma: 30-90 Hz – attentive

Question 5

What are spindles and ripples?

Answer 5

• Spindles: Periodic bursts of 8-14 Hz activity that lasts 1-2 seconds
• Ripples: Brief bouts of 80-200 Hz oscillations

Question 6

How does EEG activity change when cortex is actively engaged in processing information vs. during sleep?

Answer 6

• Processing info: Activity of neurons increases in non-synchronous way. This is because small clusters of neurons are involve in different aspects of cognition, so selective cortical activation leads to low synchrony and low amplitude waves (gamma and beta waves dominant) with high frequencies.
• Nondreaming Sleep: Neurons are physically excited by slow, rhythmic input. High synchrony of firing results in high amplitude and low frequency. Occurs in non dreaming sleep, drugged states, and pathological conditions of coma.

Question 7

What are the two ways that neurons generate rhythmic activity in the brain?

Answer 7

1. Pacemaker: A large set of neurons take their cues from a central pacemaker. For example, each thalamic neuron is a pacemaker since one AP causes an AP in thousands of other neurons in the cortex.
2. Mutual excitation / inhibition: Neurons share / distribute timing functions locally. Neurons in close proximity take signals from each other and begin firing APs at the same time.

Question 8

Explain the circuit of a simple neural oscillator in the brain.

Answer 8

• There must be constantly active excitatory input to drive the system
• Excitatory input excites E cell
• E cell excites I cell
• I cell projects back to E cell and inhibits it
• Causes neuron to fire for a bit and then go dormant
• Once activity of inhibitory cell decreases, E cell begins to fire again until I cell is turned on again

Question 9

What are the 3 basic components of neural oscillators?

Answer 9

1. Constant excitatory input
2. Feedback connections
3. Synaptic excitation and inhibition

Question 10

Explain how rhythmic activity is coordinated by a combination of both a pacemaker and collective activation.

Answer 10

• Thalamus acts as a pacemaker: Innervates the entire cortex and produces rhythmic APs
• Thalamic neurons produce rhythmic activity themselves through mutual excitation. They contain voltage-gated ion channels that allow each neuron to generate rhythmic, self-sustaining discharge patterns. The rhythmic activity of each neuron then becomes synchronized with many other thalamic cells via mutual excitation. Synaptic connections between excitatory and inhibitory thalamic neurons force each individual neuron to conform to the rhythm of the group.

Question 11

How is the rhythmic activity of the thalamus translated to the cortex?

Answer 11

• Rhythm of thalamic neurons passed to cortex via thalamocortical axons, which are excitatory
• However, many cortical populations also depend on collective, cooperative interactions amongst themselves. Excitatory and inhibitory interconnections produce coordinated, synchronous patterns of activity. Some connections are localized while others are spread to encompass larger regions of cortical neurons.

Question 12

What are 2 theories that attempt to explain the functional significance of cortical rhythms during sleep?

Answer 12

1. Rhythmic activity is a way to disconnect the cortex from sensory input. Because thalamic neurons enter self-generating rhythmic states during sleep, it prevents organized sensory input from reaching the cortex.
   - However, still doesn’t answer why rhythms are necessary and why we can’t just inhibit cortex entirely.
2. Rhythmic activity is to group different brain regions together and unite activity in various neural circuits together as one perceptual unit. By firing synchronously and rhythmically, brain can piece together related activity in response to related stimuli. High synchronous oscillations would somehow tag various regions as a meaningful group, distinct from other nearby neurons.

Question 13

What is the definition of sleep?

Answer 13

• A readily reversible state of reduced reponsiveness to, and interaction with, the environment.
• Series of precisely controlled physiological states
• Sequence of events that lead to sleep are governed by neuromodulatory systems

Question 14

What is the difference between REM and Non-REM sleep?

Answer 14

REM:

• Active, hallucinating brain in paralyzed body
• Brain looks more awake than asleep with fast, low amplitude waves
• Brain’s oxygen consumption is high
• Body (except for eyes) is immobilized (atonia)
• Respiratory muscles continue to function but barely
• Vivid, detailed illusions
• Dominated by sympathetic tone, although paradoxical drop in body temperature

Non-REM:

• Idling brain in movable body
• EEG has large amplitude, slow waves
• Dreams are less vivid and emotionally laden
• Period of rest: reduced muscle tension and minimal movement
• Energy consumption is massively reduced in body and brain and neural activity is low
• Cortical neurons are highly synchronous and most sensory input does not reach cortex
• Increased activity of parasympathetic division
• Body temperature drops

Question 15

How much of our total sleep time is spent in REM and Non-REM?

Answer 15

• Non-REM: 75%

- REM: 25%

Question 16

What is ultradian rhythm?

Answer 16

• Cycling between non-REM and REM sleep every 90 minutes

Question 17

Explain the cycle of the sleep phases.

Answer 17

• Progress from stage 1 up to stage 4 of non-REM

- Sleep then begins to lighten and ascends through stages 3-2 for 10-15 minutes before entering REM sleep

Question 18

Explain the 4 stages of non-REM sleep.

Answer 18

Stage 1: Drowsiness

• Transition from being asleep to awake
• EEG alpha rhythms become less regular
• Mix of alpha, beta, and gamma
• Eyes make slow, rolling movements
• Decrease in muscle tone, heart rate, breathing, blood pressure, metabolic rate, temperature
• Very brief (few minutes)

Stage 2: Slightly deeper and longer lasting sleep

• Spindles: Occasional 8-14 Hz oscillations that are generated by thalamic pacemaker
• K complexes: High amplitude, sharp waves can be observed
• Eye movements cease

Stage 3: Beginning of slow wave sleep

• Spindles become less frequent
• High amplitude, slow delta rhythms
• Little to no body / eye movements

Stage 4: Deepest stage of sleep

• Large EEG rhythms, very low frequency of 2 Hz or less
• Persists for 20-40 minutes

Question 19

How does the time spent in REM sleep change over a night’s sleep?

Answer 19

• As night progresses, you spend less and less time in stages 3 and 4 and more time in REM
• Half of REM sleep occurs during the last 1/3 of your sleep
• REM bouts are 30-50 minutes at most with an obligatory 30 minutes between REM bouts

Question 20

How much sleep is required each night on average? How does this change across the lifespan?

Answer 20

• Range from 5-10 hours per night with 7.5 hours average

- Individuals spend less time in REM with age: 8 hours at birth, 2 hours at 20, and 45 minutes by 70

Question 21

Name the 3 activities that can occur during non-REM sleep.

Answer 21

1. Non-vivid dreams and night terrors
2. Sleep talking (somniloquy)
3. Sleepwalking (Somnambulism)

Question 22

Name the 2 activities that can occur during REM sleep.

Answer 22

1. Vivid dreams: Everyone dreams 4-5 times per night and much more likely to remember dream if woken up during REM phase.
2. Sleep paralysis: State of partial wakefulness during REM where they are frozen and unable to move. Accompanied by an overwhelming feeling of dread, a sense of a monstrous presence in the room, and feelings of pressure or weight on the chest (common report across cultures)

Question 23

What is REM rebound?

Answer 23

• The more time that is spent in REM after deprivation is proportional to the duration of the deprivation.

Question 24

Explain the theories of Freud, Jung, and Hobson & McCarley on why we dream.

Answer 24

• Freud: Dreams are an unconscious way of expressing sexual and aggressive fantasies that are otherwise forbidden to express.
• Jung: Dreams are an expression of our collective unconscious (history of human race)
• Hobson & McCarley: Activation-synthesis hypothesis suggests that random discharges of pons during REM sleep activates cortical neurons via the thalamus. Thus, activation of the cortex elicits well-known images and emotions and the cortex attempts to synthesize it into a sensible whole.

Question 25

Explain the theory that sleep is a restorative process.

Answer 25

• Sleep deprivation impairs learning, cognitive performance, reaction time, increased risk of seizure, etc. which all point to signs of brain dysfunction (e.g., we need time to restore brain glycogen levels of astrocytes)
• Sleep deprivation / restriction not lethal. Individuals can survive seemingly forever with no sleep and there is little to no evidence for build up of toxins in sleep deprivation studies.
• If sleep were a vital physiological process, wouldn’t all animals spend roughly the same amount of time doing it?
• 2013 study showed that interstitial space volume increases during sleep. This means that there is more room between neurons and glia, which makes it easier for large, protein-based waste molecules to be eliminated from brain tissue. This occurred during naturally-occurring and drug-induced sleep, which rules out circadian fluctuations. It was specifically demonstrated in relation to beta amyloid which can form clumps outside of cell.
• Case of Randy Gardner: Stayed awake for 11 days without any long term consequences. If sleep is a restorative process, how is this possible?

Question 26

Explain the theory that sleep is a passive process.

Answer 26

• Sleep occurs as a result of a decrease in sensory stimulation
• Does not account for complexity of sleep
• No direct evidence: Sensory deprivation research has shown that people actually sleep less when placed in isolated environments and cutting off sensory afferents to brain does not abolish sleep-wake cycles.

Question 27

Explain the theory that sleep is a biological adaptation.

Answer 27

• Sleep may be an energy conserving strategy: Gather food at optimal times and sleep to conserve energy the rest of the time
• Animals with nutrient-rich diets spend less time foraging for food and more time sleeping
• Animals that are predators sleep more than animals that are prey
• Nocturnal or diurnal animals sleep during times where they cannot travel easily (e.g., humans cannot see well at night). However, this seems a bit circular – did we adapt to sleep at night because we can’t see or vice versa?

Question 28

Explain the theory that sleep plays a role in memory storage.

Answer 28

• In one study, rats showed patterns of hippocampal activity during a search for food and the same pattern of activity during non-REM sleep. This suggests that connections are acquired while awake and are replayed, strengthened, or otherwise refined during sleep (LTP)
• REM and dreaming have important role in memory: REM deprivation has been shown to impair ability to learn variety of tasks. Increases in REM after a learning experience is proportional to intensity of learning experience.
• Performance on difficult cognitive tasks has been shown to improve between evening and morning but not if REM is interrupted
• Deprivation of non-rem sleep might improve performance on learning tasks
• PET imaging: Recorded brain activity while humans performed serial reaction time task. Brain regions that were activated by the task were also active during REM sleep.

Question 29

What is sleep learning?

Answer 29

• Learning by listening to content while sleeping

- More evidence to suggest sleeping is amnesic: You don’t remember most of what happens when you sleep.

Question 30

Which diffuse modulatory systems are involved in controlling sleeping? What are the roles of each?

Answer 30

• Norepinephrine and serotonin neurons in the brainstem fire during waking and enhance wakefulness states
• Some cholinergic neurons enhance REM events while others are active when awake (different receptor subtypes)

Question 31

Diffuse modulatory systems control the rhythmic activity of neurons in which areas?

Answer 31

• Thalamus (which controls activity of cortex)

- Inhibition of motor neurons during dreaming

Question 32

What effects are seen when we lesion the brain stem?

Answer 32

• Sleep and coma

- Suggests it is involved in wakefulness and arousal

Question 33

What are the 5 systems of the Ascending Reticular Activating System? What 3 effects do their transmitters have?

Answer 33

Systems:

• Locus coeruleus (norepinephrine)
• Raphe Nucleus (serotonin)
• Brain stem (acetylcholine)
• Tuberomammillary nucleus (histamine)
• Hypothalamus (hypocretin / orexin)

Transmitters:

• Depolarize neurons
• Increase excitability of neurons
• Reduce rhythmic firing (EEG patterns change to higher frequency and lower amplitude, suggesting involvement in wakefulness)

Question 34

What effect does stimulating the cholinergic neurons in the RAS between the pons and midbrain have?

Answer 34

• Promotes wakefulness

Question 35

How does brain activity change between REM sleep and wakefulness?

Answer 35

• No change in activity of primary visual cortex
• Extrastriate cortex and limbic system become more active during REM (emotional components of dreaming)
• Frontal lobe and posterior cingulate cortex becomes less active during REM (not much interpretation of dreams)

Question 36

How does brain activity change between REM and non-REM sleep?

Answer 36

• Primary visual cortex is less active during REM (indicates that dreaming is internally driven)
• Extrastriate cortex is more active during REM (represents dreaming)

Question 37

How does diffuse modulatory system activity change over a REM cycle?

Answer 37

• Locus coeruleus and raphe nuclei activity increases just before the end of REM (involved in wakefulness)
• Cholinergic neurons of the pons increase just before REM onset (induce REM sleep)

Question 38

What neurons modulate activity of the Locus Coeruleus and Raphe Nuclei?

Answer 38

• Tuberomammillary Nucleus neurons (histamine)

Question 39

What neurons activate histamine producing neurons of TMN?

Answer 39

• Neurons in the lateral hypothalamus that express hypocretin / orexin
• Hypocretin has strong projections to cholinergic, noradrenergic, serotonergic, dopaminergic, and histaminergic modulatory systems
• Hypocretin promotes wakefulness, inhibits REM and facilitates neurons that enhance motor behaviour

Question 40

What disorder is the result of a loss of hypocretin neurons?

Answer 40

• Narcolepsy
• Excessive daytime sleepiness and sleep attacks
• Patients go from awake directly into REM
• Linked to a mutation in hypocretin receptor
• Hypocretin knockout mice display narcolepsy
• Human narcoleptic patients show a 10% reduction in hypocretin producing neurons (measured in CSF)
• Thought to be auto-immune related. Fragments of the virus mimic hypocretin and trigger immune response.
• Hypocretin can’t be used as a treatment because it cannot cross the BBB

Question 41

How does activity of the basal forebrain change during sleep and wakefulness?

Answer 41

• Activity high during wakefulness

- Decreased firing rate is associated with non-REM sleep

Question 42

What subset of neurons in the basal forebrain increase firing with onset of NREM and are silent during wakefulness?

Answer 42

• Subset of cholinergic neurons

Question 43

What are thalamocortical neurons? Where do they receive projections from?

Answer 43

• Neurons that reside in the thalamus and project to pyramidal cells in the cerebral cortex
• Receive projections from LC, Raphe, and TMN

Question 44

What are the 2 states that thalamocortical neurons can exist in?

Answer 44

1. Intrinsic bursting /oscillatory state: Mutual excitation causes neurons in the thalamus to become synchronized with neurons in the cortex. This disconnects the cortex from the outside world, and this disconnection is maximal during slow wave sleep.
2. Tonically active state: State that is generated when neurons are depolarized. Afferent inputs come in from external stimuli and they transmit information to cortex. Induced by activity from cholinergic or monoaminergic projections from brainstem nuclei.

Question 45

What type of cell in the thalamus is involved in hallucinations?

Answer 45

• Reticular thalamic cell
• Activation of these cells can inhibit thalamocortical cells so that synchronous firing of the cortex cannot be generated. This results in hallucinations.

Question 46

What is the role of Adenosine in sleep?

Answer 46

• Used by all cells to build essential building blocks and builds up inside cells as a consequence of cellular processes – levels gradually decrease during sleep
• Adenosine has inhibitory effects on diffuse modulatory systems for Each, NE, and 5-HT that promote wakefulness
• Sleep may be a molecular chain reaction. Neural activity when awake increases adenosine levels, which increases inhibition of diffuse modulatory systems associated with wakefulness. This produces slow-wave synchronous activity that is characteristic of NREM. Once sleep, adenosine levels gradually fall and activity of modulatory systems increase until we are awake.
• Caffeine works because its molecular structure is very similar. It blocks adenosine receptors are promotes wakefulness.

Question 47

What is the role of Nitric Oxide in sleep?

Answer 47

• Levels rise with wakefulness and are highest with sleep deprivation
• Wake-promoting cholinergic cells express high levels of the enzyme responsible for NO production
• NO may promote adenosine release