Physiology of sleep & consciousness

Definitions:

• SLEEP
• reversible behavioral state of unresponsiveness & perpetual dissociation from the environment
• CONSCIOUSNESS:
• Perception of sensations, voluntary initiation & control of movement, capabilities associated with higher mental processing

Stages of consciousness

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Sleep

• Not a period of absolute rest
• some parts of the brain are more active during sleep
• Dreams
• necessary
• Experiments where people have been awakened as they enter the REM sleep phase become moody & depressed, and disoriented; and may have hallucinations
• Purpose of sleeping
• Restorative
• especially slow wave sleep
• Conservation of energy
• Maintaining adequate function of the immune system
• Mentally practise & refine behaviour
• e.g. escaping from predators without actually having to perform them
• REM sleep
• we dream to forget
• reverse learning helps us forget trivial things
• and to sort out our emotions
• Physiological changes in sleep
• Decreased reaction to external stimuli
• Reduced activity of the sympathetic system
• Parasympathetic dominance
• Reduced heart rate, BP, respiratory rate
• especially in Non-REM sleep
• Reduced metabolic rate
• Somnolent Metabolic Rate (SMR)
• is lower than BMR
• Reduced muscle tone
• Extensor  Babinski response
• unmasking of extensor dominance
• Changes in EEG
• Increased growth hormone production during deep sleep
• decreased in REM sleep

Sleep cycles

• First cycle:
• descends from stage 1-2-3-4
• resurfaces from 3-2-1
• enters REM-descends intom2-3-4 and so on
• Subsequent cycles become shorter
• The cycle ends with REM sleep
• In adults, sleep begins with NREM
• in infants it begins with REM
• REM-onset sleep is seen in adults in
• jet lag
• chronic sleep deprivation
• acute withdrawal of REM-suppressing drugs
• endogenous depressinarcolepsyon
• Retrograde amnesia
• poor recall of midnight dreams
• not remembering clock ringing

• Awake
• Alert
• Beta wave
• Resting
• Alpha wave
• Sleep
• Stage 1
• Theta wave
• Stage 2
• Spindles
• K complex
• Stage 3
• Delta wave appears
• Stage 4
• Delta wave
• Also seen in deep sleep/ anaesthesia / brain damage in awake adults
• Synchronisation
• REM Sleep
• Ponto-geniculo-occipital (PGO) spike

Difference between deep sleep and REM sleep

Changes in pattern of sleep with age

• With age
• REM sleep decreases
• deep sleep decreases
• Total sleep time decreases

Regulation of sleep

• Sleep is regulated by
• an interaction of homeostatic and circadian processes
• The homeostatic mechanisms
• keep track of how long we have been awake and asleep
• how tired we are!
• The circadian process
• determines the optimal time for sleep
• They influence sleep duration and the relative contribution of the two major types of sleep:
• non-rapid eye movement (NREM)
• rapid eye movement (REM) sleep

The circadian process

• Circa=about , dian=day
• The suprachiasmatic nucleus (SCN) dictates the sleep-wake cycles over a roughly 24-hour period
• the SCN receives inputs via the retino-hypothalamic fibres
• is  influenced by external cues (e.g daylight)
• but the rhythm is still present in volunteers kept in caves or in people blind from birth
• Light initiates sleep in nocturnal animals & waking in diurnal animals (including humans)
• Melatonin & melanopsin may play a role
• Phase shifts can occur with rapid crossing of time zones
• resulting in ‘jet lag’

The ultradian process

• that is characterized by the alternation of the two basic sleep states non-rapid-eye-movement (NREM) sleep and REM sleep
• influenced by SCN input

• Nucleus reticularis pontis oralis – have 4 nuclei
• PGO-on
• causes PGO spikes associated with REM sleep
• REM-on (stimulatory)
• atonia of muscles during REM sleep
• REM-on (inhibitory)
• inhibits the 2 nuclei inhibiting PGO-on
• REM-waking on
• eye movements
• muscle twitches
• Hypothalamus – have 1 nuclei
• NREM-on

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Sleep disorders

• Transient relief with “sleeping pills”
• benzodiazepines
• but daytime performance may be compromised

Insomnia

• Definition
• chronic inability to maintain the amount/quality of sleep to function normally in the day
• due to medical or mental conditions
• Right amount of sleep
• sleep requirements vary from 4-9 hours between individuals
• Margaret Thatcher & Napoleon need(ed) only 4 hours of sleep
• Fatal familial insomnia
• autosomal dominant inheritance
• Features
• worsening insomnia
• impaired ANS & motor functions
• dementia
• death
• Types of insomnia
• Onset sleep insomnia
• difficulty in falling asleep initially
• associated with anxiety disorders
• Maintenance sleep insomnia
• wake up middle of the night
• difficulty in remaining asleep
• with frequent awakening at night
• may get back to sleep
• associated with
• pain disorders
• medical illness
• Terminal (late) insomnia
• persistent early morning awakening
• cannot get back to sleep
• characteristic of clinical depression

Sleep deprivation

• Marked by brief psychosis but non-permanent psychological effects
• Features
• irritability
• stimuli misperception
• decreased waking alpha activity
• disorientation
• lack of attentiveness
• Neurological consequences
• tremors
• seizures

Narcolepsy

• Definition
• a chronic neurological disorder caused by the brain’s inability to regulate sleep-wake cycles normally
• excessive daytime sleepiness (EDS)
• Narcolepsy results from
• disease processes affecting brain mechanisms that regulate REM sleep
• For normal sleepers a typical sleep cycle is about 100 – 110 minutes long, beginning with NREM sleep and transitioning to REM sleep after 80 – 100 minutes
• But, people with narcolepsy frequently enter REM sleep within a few minutes of falling asleep
• Three other major symptoms frequently characterize narcolepsy
• Cataplexy
• the sudden loss of voluntary muscle tone
• Vivid hallucinations
• during sleep onset or upon awakening
• Brief episodes of total paralysis
• at the beginning or end of sleep 

Somnambulism (sleep walking)

• more common in
• children
• males
• may last a few minutes
• walk with eyes open
• to avoid collision
• but cannot remember anything
• Occur during arousal from slow wave sleep
• somnambulism
• noctural aneuresis
• bed-wetting
• night terrors
• Nocturnal emission
• Wet-dreams
• normal in male (sometimes females) of reproductive age

Sleep apnoea

• Definition
• stopping of breathing for short periods
• typically between 10 and 90 seconds) during a normal nightly sleep
• Can be repeated hundreds of times during a sleep period
• Almost always accompanied by
• snoring, which is usually quite loud
• Patient is  unaware of this happening, in normal circumstances
• 3 types of sleep apnoea
1. Obstructive sleep apnoea (OSA)
• Fairly common
• upper airway collapses as the throat muscles relax during normal sleep
• cerebral hypoxia results in waking up
• may be repeated every 15 minutes
• May result in
• excessive daytime tiredness and a lack of concentration
• Counter-measure
• Relieve the obstruction
• sleep on the side; reduce weight
2. Central
• Rare
• Neurological dysfunction
• the brain simply "forgets" or "delays" to send the signal to breathe
• More difficult to treat
• some drugs may help
3. Mixed
• Extremely rare

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Reticular Activating System (RAS)

• The reticular formation resides in the brain stem
• midbrain, pons & medulla
• Comprised of the
• motor system (reticulospinal system)
• sensory systems (RAS)
• the vital centres
• The RAS stimulates the whole brain to cause arousal (wakefulness)
• its output is suppressed in sleep & coma
• stimulated by
• input from the cortex (corticofugal fibres)
• OREXINS
• peptides released by hypothalamic neurons just before waking

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Consciousness

• Various definitions
• mind
• awareness
• ability to respond
• Can it be equated to activity in the EEG?
• Sometimes, people under general anaesthesia feel the pain and are conscious of their surroundings
• but cannot convey this to the outside world , trapped in their own body
• Perception of sensations, voluntary initiation & control of movement, capabilities –> associated with higher mental processing
• The brain’s ability to adjust its activity and consciousness levels can be impaired in several ways:
• When people are severely deprived of sleep
• When and immediately after a seizure occurs
• When both cerebral hemispheres are suddenly and severely damaged
• When the reticular activating system malfunctions
• When blood flow or the amount of nutrients (such as oxygen or sugar) going to the brain decrease
• When toxic substances impair the brain (liver & kidney failure)
• Drugs
• morphine
• diazepam
• antipsychotic drugs
• Periods of impaired consciousness can be short or long. The level of impairment can range from slight to severe:
• Lethargy
• slight reduction in alertness or clouding of consciousness
• People tend to be less aware of what is happening around them and to think more slowly
• Obtundation
• moderate reduction in alertness or clouding of consciousness
• Stupor
• excessively long or deep sleep-like state
• A person can be aroused from it only briefly by vigorous stimulation
• such as repeated shaking, loud calling, pinching, or sticking with a pin.
• Coma
• state of complete unresponsiveness
• A person cannot be aroused at all
• A person in a deep coma lacks even the most basic responses, such as avoidance of pain
• although reflexes may be present

Coma (read coma lecture notes)

• In coma, brain oxygen utilisation is below normal resting levels
• in sleep, the brain is active and oxygen consumption is comparable to the waking state
• Caused by
• trauma
• tumours
• metabolic disorders
• hypoglycaemia (hyperosmolar coma)
• drug overdose
• liver and kidney failure
• fluids & electrolytes imbalance
• hypernatraemia
• hypokalaemia
• water intoxication
• myxoedema
• Depression of the reticular activating system (RAS)
• Clinically assessed using Glasgow Coma Scale (GCS)
• Four Score Coma Scale
• eye & motor responses
• brain stem reflexes
• respiration.
  Total unresponsiveness to sensory stimuli for an extended period

Source: anatomyguru.in

Modifying memories during sleep:

Mice can recall artificial memories created during sleep once they’re awake, researchers from the French National Center for Scientific Research (CNRS) and their colleagues reported today (March 9) in Nature Neuroscience. The findings support a causal role between the firing of specialized neurons called place cells and the ability of these neurons to represent a particular location in space. Place cells, part of the brain’s “inner GPS,” were first discovered by John O’Keefe, who last year shared the Nobel Prize in Physiology or Medicine.

“This was a fantastic, well-thought-out idea that, miraculously, worked,” said neuroscientist György Buzsáki of the New York University Neuroscience Institute who was not involved with the work. “The study shows that the emotional value of a particular [location] can be modified, and, what is most critical, is that this can happen in a subconscious, sleep state.”

Karim Benchenane, a neuroscience researcher at CNRS and ESPCI-ParisTech and his colleagues first identified a single place cell in the hippocampus of each mouse that fired when the animal was in a specific location and measured the average time each mouse spent in that location prior to any manipulation.

Then, when that particular place cell became spontaneously active during either an awake or sleep state, an automatic stimulation of the medial forebrain bundle—a part of the brain associated with positive reward sensations—was executed through a brain-computer interface. This stimulation has long been known to result in the release of dopamine neurotransmitters, similar to what happens when the mouse receives a food or some other reward. Each mouse received the stimulation either during an awake or sleeping state, but not both.

This linking of a specific place cell with rewarding stimulation resulted in the animals spending about five times more time in the location associated with the place cell activity compared to the time they spent in that location prior to the stimulation experiment.

When this link between the place cell and reward trigger occurred during sleep in a second set of mice, the animals were more likely to go directly to the location associated with that place cell upon waking.

“The animal developed a goal-directed strategy for the [location], as if the animal had a conscious recollection that there was a reward there,” explained Benchenane.

The activity of place cells during sleep has been previously interpreted as the replay of the places the animal has visited when awake. “Scientists had thought that during sleep, representations of waking experiences get reactivated, and this finding clearly suggests this is the case,” said Kate Jeffery, a behavioral neuroscientist at University College London who was also not involved in the study.

In awake animals, the activity of place cells has been associated with being in a specific location, but so far, it has been difficult to directly attribute place cell activity to a representation of that physical location by the animal’s brain. Focusing on the animal’s place cell activity during sleep, when only replay is active, Benchenane and his colleagues were able to directly link place cell firing to spatial navigation. Their results also provide evidence that the activity of place cells during sleep does indeed convey the same spatial information during an awake state. This is consistent with the idea that recent spatial memories are strengthened during sleep, noted Jeffery.

“This is the first example of memory manipulation during sleep,” said Buzsáki. “The ideas in this study support the probably 100-year-old idea that it is possible to put false memories in the brain.”

More details: http://www.the-scientist.com/?articles.view/articleNo/42362/title/Modifying-Memories-During-Sleep/