Sleep, wakefulness and the EEG

Zeitgebers

A stimulus (like the light of dawn or an alarm clock) that resets the biological clock responsible for circadian rhythms. You would still sleep if it was constantly light outside. Can reset internal clock

The thalamus

A synaptic target common to all these systems is the thalamus The thalamus is richly connected with the cerebral cortex and is known to modulate its arousal If can modulate thalamus can modulate cortex

EEG -REM

Fast Beta waves and REM Subject easier to rouse than in stage 4 Dreaming, recalled, plus low muscle tone Suddenly becomes much more active Rapid eye movements Easy to rouse Can remember dreams Takes an hour to get to REM

EEG - stage 3

Few mins duration Has slower frequency delta waves (inc amplitude) appear Harder to rouse. Few spindles. Properly asleep Cells are entrained into v nice rhythmicity, hard to awaken Sleep spindles disappearing - transient affect

Sleep spindles

Short bursts of rapid brain waves that start to appear in stage 2 sleep

Reticular formation

1. Diffuse collection of at least 100 networks of neuromodulatory neurones spanning all 3 divisions of the brainstem -it is not homogeneous -has diverse functions (posture, respiration, HR and sleep/arousal) 2. It has projections to: -the thalamus -hypothalamus -some brainstem nuclei -cerebellum -spinal cord -cerebral cortex 3. It receives input from: -the cerebra (collaterals from the corticospinal pathways) -the visual and auditory systems -sensory spinal systems -cerebellum -certain brainstem nuclei

EEG waves and the thalamus

1. Lesioning the thalamus abolishes (most) synchronous EEG waves 2. Rhythmic stimulation of the thalamus induces stage 4 sleep (high amp, low frequency waves) 3. Certain EEG wave types can be changed (for example from alpha to beta - increasing alertness) by activation of the reticular formation and so the thalamus

EEG - stage 2

10-15 mins duration Have K complexes and sleep spindles (8-14Hz bursts) No eye movement but body movement remains possible Increase in rhythmic discharges

Sleep and Wakefulness control

1. Reticular formation is excited -causes depolarisation (excitation) of thalamus -thalamus gives non-rhythmic output -this increases arousal (alpha waves to beta waves) 2. Inhibition of reticular formation -hyperpolarisation (less excited, dulled) of thalamus -thalamus gives rhythmic output -get slow EEG waves in cerebral cortex (like stage 4 sleep)

Sleep and consciousness

1. Sleep is usually described in relation to consciousness a) easily reversible state of inactivity with a b) lack of interaction with the environment 2. Unconsciousness is an inconsistent term, it can be: -coma (depressed state of neural activity) -sleep (variation in neural activity, specific to it) 3. Consciousness has been described as having 3 states

Externally discernable sleep

2 main forms: 1. when the eyes move rapidly from side to side (REM sleep) or 2. When they do not (nonREM, slow wave or deep sleep) however there are other determinants also Neuronal activity during different stages of wakefulness (including sleep) can be measured using an EEG

Consciousness

3 states 1. Wakefulness -animal is alert, detects objects and pays attention to them 2. Core consciousness -wakefulness, plus emotional responses, and simple memory 3. Extended consciousness -all of the above plus self-awareness autobiographical memory, language and creativity All three of these states can happen following various degrees of nervous damage

EEG electrodes

Arranged in 19 pairs (or more) at internationally agreed points on the surface of the head Comparison between the pairs of electrodes provides a coarse picture of the neuronal activity in the various areas of the brain. There are numerous types of comparison used, as well as more complicated and dense networks of electrodes EEG recordings allow the separation of REM and non REM sleep, and for the latter to be subdivided into a further four stages of sleep, each with its own characteristic brain wave patterns Can watch info moving around the brain

Recap of thalamic function

Broadly speaking, inhibiting the thalamus decreases the sensory throughput and exciting the thalamus increases the sensory throughput Specific site, and general excitability of the thalamus can be controlled by the reticular formation via a number of pathways The thalamus acts as a major relay between the sensory systems (including sight) and the cerebral cortex

Control of Non-Rem

Characterised by synchronised cortical slow waves caused by hyperpolarised thalamus and decreased activity in the arousal centers of the reticulum Sleep spindles and K complexes are caused in part by the inherent rhythmicity of thalamic neurons as they hyperpolarise due to reduced ascending reticular formation input. Seen in non-REM stage 2 sleep As thalamic cells hyperpolarise further, they develop slow wave rhythmicity (due to thalamic interconnections) which serves to block ascending sensory input. This rhythmicity is transmitted to the cortex and due to strong reciprocity between these 2 areas, the waves become synchronised across the cortex.

A typical nights sleep

Consists of several cycles through the 5 stages of sleep Note that stage 4 is only reached in the initial cycles, thereafter the deepest sleep attained is stage 3. Increasing amount of time spent in REM sleep. Eye movement is slow and rolling in the 1st stage and rapid in REM, muscle activity (head) decreases with depth of sleep REM is also characterised by increases in HR, neural activity and respiration and O2 consumption

REM sleep

Contrast to non-REM 1. The brain is very active and is most likely to be dreaming (95% likelihood), but the body is effectively paralysed 2. One source of activity is concerned with inhibiting motor output (excepting breathing and eye movement) -locus coeruleus in brainstem inhibits movement. Centres in the midbrains that inhibit descending midbrain by acting on collaterals of corticospinal pathways 3. Body temp drops as metabolism is inhibited

REM cycle

Cycle from Stage 1 through 4 and REM Should do cycle 4/5 times during the night REM sleep is how you count the quality of your sleep All stages of sleep are important but cycling is what determines good nights sleep From drowsy to deep sleep takes about 1 hour, duration of REM sleep is variable On average 5 REM sleeps per night Minimum time between REM sleeps seems to be about 30 mins Amplitude is determined by how many cells are synchronised - awake, all cells integrating info and are synchronised

Circadian rhythms

Daily behavioral or physiological cycles that involve the sleep/wake cycle, body temperature, blood pressure, and blood sugar level Influence the flip-flop switch

EEG - stage 4

Deepest sleep Hardest to rouse >50% EEG waves at 2Hz and high amplitdude (>200microvolts) called delta waves Heart rate and BP lower, movement 15-30min period V hard to wake them up Movements limited - paralysed Cant remember what are dreaming about

Sleep deprivation

Depression which can cause the subject to be concerned about trivial illness/pain Muscle aching Clumsiness Absent mindedness Immune system isnt repairing properly - increased propensity to get ill

EEG - stage 1

Duration - 1-5 mins Easily aroused Slow rolling eye movements Some theta waves (slower frequency 4-7Hz) and higher amplitude waves Cells become slightly more synchronised as fall asleep

Somnambulance

During non-REM sleep Often the same as REM sleep behaviour disorder but there is no memory of the dreams enacted. Occurs in nonREM sleep which is why there is no memory, and happens when the midbrain reticular formation fails to paralyse the body

Electroencephalogram

EEG An amplified recording of the waves of electrical activity that sweep across the brain's surface. These waves are measured by electrodes placed on the scalp. Post synaptic activity of individual neurons not picked up Post synaptic activity of synchronised dendritic activity can be picked up (groups of neurons). Synchronisation is either by neuronal interconnections (mexian wave) or by pacemaker (orchestrator of mexican wave) The more neurons that are synchronised, the bigger the peaks on the EEG

EEG - awake

Eyes closed - Alpha waves High frequency (8-13Hz) and low amp (50microV) Eyes open - Beta waves 14-60Hz) Waves of activity

Wakefulness

Interconnection concerning wakefulness between: 1. the elements of the reticular formation of the brainstem 2. the thalamus 3. the cerebral cortex

Locus coeruleus

Is a nucleus in the pons involved with physiological responses to stress and panic. The locus coeruleus is the principal site for brain synthesis of norepinephrine (noradrenaline).A small nucleus in the reticular formation involved in attention, sleep, and mood The locus coeruleus is a part of the ascending reticular activating system, and is almost completely inactivated in rapid eye movement sleep.

Penile erection

Is associated with REM sleep and this characteristic can be used in discrimination between different types of erectile dysfunction (physical or psychological)

Cataplexy

Loss of muscle control with intrusion of REM sleep during waking hours, usually caused by an emotional trigger

REM sleep behaviour disroder

Most common in males Often act out their dreams and either sustain or give repeated injuries Occurs during REM sleep and happens when the descending pontine reticular formation fails to properly immobilise the body Characterised by rapid/violent movement and behaviour Motor activity carries on down and can be acted on

Sleep

Most vertebrates, and all mammals sleep, but not all sleep the same way as humans eg dolphins v seals v humans The true function of sleep is unknown: -suggested functions include the processing and storage of memories During sleep the neurons of the brain are active, but displays a different type of activity from wakefulness, and sometimes more The sleeping brain consumes as much oxygen as the wakeful brain and sometimes more

General inputs to the thalamus

Nucleus Basilis Spinoreticular pathway - from lateral spinothalamic tract Midbrain reticular formation Vestibulocohclear nucleus (VIII) Spinal nucleus V (trigeminal) Feed onto thalamus, multiple lobes are reciprocally innervated onto cortex

Narcolepsy

Occurs around age 20-30yrs Onset due to specific loss of Orexin containing neurons in the lateral hypothalamus Thought to be an inherited autoimmune condition linked to chromosome 6. Presents as tetrad of symptoms: 1. Repeatedly falling asleep during the day, regardless of current activity 2. Limb weakness during emotional episodes (mild to extreme cataplexy) - emotional overlay. Heightens emotions as about to fall asleep too. 3. Night time or morning wakening accompanied by muscular paralysis (sleep paralysis) 4. Vivid dream recollection just prior to wakening (come up directly from REM sleep)

REM sleep behaviour disorder

Occurs during REM sleep and happens when the descending pontine reticular formation fails to properly immobilise the body Characterised by rapid/violent movement and behviour

Orexin

Orexinergic neurons are normally active during wakefulness (lateral hypothalamus) These neurons project to the cerebra, the arousal nuclei and the VLPO however the VLPO has no orexin receptors Therefore these neurons enhance the arousal nuclei and by doing so cause indirect inhibition of VLPO via reciprocal pathways between arousal centres and the VLPO. Orexin is therefore pivotal in the sleep/awake switch circuitry and adds stability to the mechanism

Narcoleptics

Pass directly from awake state to REM sleep Some suffer from bouts of cataplexy during emotional episodes - mimics sleep paralysis This is caused by the pontine influence (locus coeruleus) of muscle tone during REM

Arousal Pathways

Pathway 1 Dependent on thalamic gating: -midbrain reticulum projects cholinergic excitation onto the thalamus. Only strong signals pass through. -pathway is nearly always On. -Only inactive in nonREM sleep. -these inputs facilitate thalamo-cortical transmission when awake. Pathway 2 Direct Cortical excitation: -excitatory nodes which all feed up to cortex, independent of thalamus, proving direct cortical excitation -quiescent during REM -some firing during nonREM and most when awake -lesions here cause extreme sleepiness and coma -receives input from lateral hypothalamus orexin (ORX arousal stability) or Basal forebrain neurons containing GABA or Ach (alzheimer's) pivotal in flipping from awake to asleep pathway

Control of REM sleep

REM has been likened to a "highly active hallucinating brain in a paralysed body" During REM this is a high descending motor output which is blocked by the brainstem (locus coeruleus) Exceptions are the motor systems controlling the eyes, middle ear and the respiratory centres During REM, cholinergic neurons of the midbrain reticular formation excite the thalamus, and provide descending inhibitory stimuli to the motor pathways NB. EEG traces, show a high degree of similarity between these REM and awake stakes Uses more oxygen than a brain engaged in a complex cerebral problem.

Insomnia

Sleep disorder 2 forms of permanent insomnia 1. Rare inherited neurodegenerative process affecting the thalamus and the rostral hypogenic (sleep centres). Cant turn flip flop switch 2. Stroke resulting in blockade of basilar artery. These pts are typically suffering from locked in syndrome and have control only over ocular movement If the resultant neuronal damage includes the loss of the pontine hypogenic centre the result can include incomnia

Flipflop

Switching between arousal and sleep Moving from awake to asleep is fast, as is waking up - flip flop switch Increasing pressure on one side moves the switch closer to the point of transition When the point of transition is reached the switch flips over to the alternate state

Arousal centers

The arousal system involves many different neural systems. Five major systems originating in the brainstem, with connections extending throughout the cortex, are based on the production of brain's neurotransmitters: acetylcholine, norepinephrine, dopamine, histamine, and serotonin. When these systems are in action, the receiving neural areas become sensitive and responsive to incoming signals, producing alertness and cortical activity. Turn off NT to prevent arousal

Suprachiasmatic nucleus

The suprachiasmatic nucleus (SCN) is located in the hypothalamus and controls: 1. Circadian cycles 2. Influences many physiological and behavioural rhythms occuring over a 24-hour period, including the sleep/wake cycle In humans "free running" of the SCN clock gene gives a periodicity of about 24.5 hours This cycle is therefore re-set each day by a variety of Zeitgebers (time givers), the most dominant of which is the light dark cycle Receptors in the retina (not rods and cones) containing melanopsin react to light and synapse directly onto the SCN resetting the clock gene - can turn orexin centres off.

Sleep pathway

The ventrolateral pre-optic nucleus (VLPO) has been identified as the centre of non REM sleep promotion It has inhibitory projections to all the major direct arousal centres and is active during sleep The VLPO also innervates neurons in the lateral hypothalamus (including orexin neurons) and interneurons in the Midbrain reticular formation (MRF) cell groups The extended VLPO (area around the VLPO) promotes REM sleep, and the VLPO cluster promotes NREM sleep The VLPO is reciprocally inhibited by projections (NA, GABA and 5HT) from the arousal centres. Arousal centres trying to fight against VLPO inhibition

RF involvement in sleep

There are arousal centres in the brainstem which project fibres to a wide variety of structures in the brain including the thalamus These projections belong to one of these 3 neurotransmitter groups: -norepinephrine -serotonin -acetylcholine Lesion of any one of these neuronal systems results in either coma or stupor ie the release of these NT's from neurons of the RT are required for consciousness

Beta waves

These are known as high frequency low amplitude brain waves that are commonly observed while we are awake. They are involved in conscious thought, logical thinking, and tend to have a stimulating affect. Having the right amount of beta waves allows us to focus and complete school or work-based tasks easily. Having too much beta may lead to us experiencing excessive stress and/or anxiety. The higher beta frequencies are associated with high levels of arousal. When you drink caffeine or have another stimulant, your beta activity will naturally increase. Think of these as being very fast brain waves that most people exhibit throughout the day in order to complete conscious tasks such as: critical thinking, writing, reading, and socialization.

Delta waves

These are the slowest recorded brain waves in human beings. They are found most often in infants as well as young children. As we age, we tend to produce less delta even during deep sleep. They are associated with the deepest levels of relaxation and restorative, healing sleep. They have also been found to be involved in unconscious bodily functions such as regulating heart beat and digestion. Adequate production of delta waves helps us feel completely rejuvenated after we wake up from a good night's sleep. If there is abnormal delta activity, an individual may experience learning disabilities or have difficulties maintaining conscious awareness (such as in cases of brain injuries).

Alpha waves

This frequency range bridges the gap between our conscious thinking and subconscious mind. In other words, alpha is the frequency range between beta and theta. It helps us calm down when necessary and promotes feelings of deep relaxation. If we become stressed, a phenomenon called "alpha blocking" may occur which involves excessive beta activity and very little alpha. Essentially the beta waves "block" out the production of alpha because we become too aroused. Frequency range: 8 Hz to 12 Hz (Moderate) Too much: Daydreaming, inability to focus, too relaxed Too little: Anxiety, high stress, insomnia, OCD Optimal: Relaxation Increase alpha waves: Alcohol, marijuana, relaxants, some antidepressants

Theta waves

This particular frequency range is involved in daydreaming and sleep. Theta waves are connected to us experiencing and feeling deep and raw emotions. Too much theta activity may make people prone to bouts of depression and may make them "highly suggestible" based on the fact that they are in a deeply relaxed, semi-hypnotic state. Theta has its benefits of helping improve our intuition, creativity, and makes us feel more natural. It is also involved in restorative sleep. As long as theta isn't produced in excess during our waking hours, it is a very helpful brain wave range.

Non-REM sleep

Waves during slow wave or non-REM sleep 1. As the subject goes deeper into non-REM sleep, movement and breathing is depressed however movement is still possible. Brainstem suppresses - active process 2. At stage 4 the brain shows slow waves of synchronised firing of large groups of neurones 3. There is more than one alpha wave subtype (visual cortex - (classic type), sensory motor cortex (mu type) and the auditory (kappa type)) with the occipital being the most prominent (standard, shows change from alpha to something else) Slow waves are thought to be involved with inhibiting sections of the relevant cortex.

Orexin mechanism

When orexin is released it stimulates the arousal centres and so causes inhibition of the VLPO. As long as orexin is released the balance is shifted towards wakefulness. When the VLPO begins to fire, it inhibits both the orexinergic neurons and the arousal centres This: 1. removes the inhibition of VLPO by the arousal centres and 2. cuts off the excitation from the orexinergic neurons thus pushing the balance quickly towards sleep.