Sleep and Epilepsy Mecanism

Basic Mechanisms of Sleep

• Remedios Varo painted Insomnio I and Insomnio II in 1947.
• The pharmaceutical company Bayer commissioned these gouache on cardboard works to illustrate disorders like insomnia.
• Insomnio I depicts a series of eyes emerging from doors in an endless succession of rooms.
• Insects with crystalline wings are drawn to the light of a lit candle, symbolizing sleeplessness and nocturnal anxiety.

Historical Views of Sleep

• Sleep was once viewed as a state resembling death.
• Sleep's purpose may explain why people pray before sleeping.
• The Aristotelian view is that sleep is caused by "fumes" from the food we eat.
• In the Middle Ages, tiredness was thought to decrease the amount of "ether of life" produced by oxygen inhalation, which eventually causes sleep.

Theories of Sleep

• Passive theory says sleep is a brain state caused by decreased sensory stimulation, marking the end of wakefulness.
• Bremer's experiment "cerveau isole" involved midbrain transection resulting in an high voltage slow wave EEG pattern, constricted pupils, similar to sleep.
• "Encephale isole" involved transection between the caudal medulla and spinal cord, resulting in a normal sleep - wake cycle.
• Sleep is an active process where different brain structures actively participate in the sleep-wake cycle.

The Electroencephalogram (EEG)

• Different EEG frequencies are associated with different states.
• Beta waves range from 14-50 Hz, have a "synchronized pattern", and an amplitude of 5-10uV.
• Alpha waves range from 8-13 Hz, have a "synchronized pattern", and an amplitude of 10-15uV.
• Delta waves range from 0.3-3 Hz and have an amplitude of 20-200 uV.
• Theta waves range from 3-10 Hz and have an amplitude of 100-300 uV.

Sleep Stages

• The 2 major sleep stages are non-rapid eye movement (NREM or slow wave sleep) and rapid eye movement sleep (REM).
• There are 4 major stages in NREM sleep.

Stage 1

• Drowsiness is the characteristic.
• Entering sleep.
• Alpha waves start to disappear.
• Theta waves and deeper, more regular respiration appear.

Stage 2

• Light sleep.
• "Sleep spindles" appear.
• Muscle tone and autonomic nervous system are depressed.
• There is a high sensory threshold.
• K complex is present.

Stage 3

• Deep sleep.
• Some delta waves appear.
• Higher sensory threshold.
• There is a major decrease in muscle tone and autonomic nervous system activity.

Stage 4

• Mainly composed of delta waves.
• Essentially like in Stage 3.

REM Sleep

• It primarily consists of beta waves.
• Beta waves are typically associated with wakefulness, hence the name "paradoxical sleep".
• Dreaming is usually associated with REM sleep.
• Active inhibition of muscle tone and some phasic muscle activity (muscle twitches) is present.
• Thermoregulation is absent.
• Heart rate and respiration become irregular.
• There are bouts of rapid eye movement.
• The autonomic nervous system is generally depressed, but periodic increases in autonomic activity can occur, causing tachycardia, elevated blood pressure, penile erection, etc.

Architecture of a Night's Sleep

• NREM and REM alternate, with REM occurring at regular intervals 5-7 times per night.
• The intervals between successive REM periods decrease after the first REM, while the length of REM periods increases.
• REM occupies 20-25% of sleep time in young adults.
• REM is more prominent in infants (occupies approximately 50% of sleep time) and decreases with age.

Physiological Changes During Sleep

• Heart rate decreases during NREM sleep and is irregular with increases and decreases during REM sleep.
• Blood pressure is unchanged and stable during NREM, but irregular with increases and decreases during REM.
• Respiration decreases in rate during NREM and is irregular in rate during the phasic stage of REM.
• Ventilation decreases in tidal volume with a decreased hypoxic response during NREM, and decreases in tidal volume within the phasic stage, along with a decreased hypoxic response during REM.
• Upper airway muscle tone decreases during NREM and is further decreased during REM.
• Temperature exhibits preserved thermoregulation during NREM but increased temperature and poikilothermia during REM.
• Pupils are constricted during NREM and are constricted in the tonic stage but dilated in the phasic stage of REM.
• Gastrointestinal function involves failure of inhibition of acid secretion with prolonged acid clearance during NREM, and failure of inhibition of acid secretion during REM.
• Nocturnal penile tumescence/clitoral enlargement is infrequent during NREM but frequent during REM.

Sleep in Cetaceans

• Cetaceans exhibit unihemispheric slow waves during sleep.
• EEG recordings of cetaceans show unihemispheric slow waves.
• Top traces display left and right EEG activity.
• Spectral plots indicate 1-3 Hz power in the two hemispheres.

Consequences of Total Sleep Deprivation

• Total sleep deprivation in experimental animals can lead to dire consequences.
• Experimental rats are kept awake by triggering floor movements upon the onset of sleep.
• Control rats are able to sleep intermittently.
• After 2-3 weeks of sleep deprivation, experimental the experimental animals lose weight, fail to control body temperature, and eventually die.

Importance of Glymphatic System

Glymphatic System is a functional waste clearance pathway for the mammalian central nervous system (CNS), dependence on astrocytic aquaporin 4

Effect of Wakefulness and Adrenergic Signaling on CSF Influx

• Wakefulness suppresses the influx of CSF tracers.
• Adrenergic signaling modulates cortical neuronal activity and the volume of interstitial space.
• Adrenergic inhibition increases CSF influx in awake mice.

REM Deprivation

• It is difficult to achieve because of pressure to restore lost REM sleep.
• REM rebound occurs when individuals make up for lost REM sleep as soon as possible, shortening the latency to the first REM period.
• REM deprivation for a few nights usually is effective in treating depression, and does not lead to psychosis.

Brain Areas Important For Sleep

• VLPO (GABA, Gal)
• PeF (ORX)
• VPAG (DA)
• TMN (HIS)
• Raphe (5-HT)
• PPT (ACh)
• LC (NA)

Circadian Effects on Wakefulness and Sleep

• Retinal photosensitive ganglion cells stimulate the suprachiasmatic nucleus, which then stimulates the hypothalamus near the fornix (OREXIN).
• VPLO activates in the dark, it inhibits TMN, LC and 5-HT
• Allowing NREM to occur

Possible Functions of Sleep

• Rest and restitution
• Conservation of energy (decreased metabolism), and protection
• Learning and memory
• Waste clearance
• Psychological