The document discusses biological rhythms and sleep-wake cycles. It describes circadian rhythms controlled by the suprachiasmatic nucleus and influenced by factors like light and temperature. Two drives regulate sleep - a homeostatic drive that increases with wakefulness, and a circadian drive controlled by the suprachiasmatic nucleus. Neurons in the ventrolateral preoptic nucleus promote sleep by inhibiting wake-promoting areas. The document also discusses EEG patterns in different sleep stages, including spindles in stage 2 and delta waves in stage 3. It mentions the role of orexin/hypocretin neurons in maintaining wakefulness and inhibiting REM sleep.

1. ‫خواب‬ ‫و‬ ‫زیستی‬ ‫های‬ ‫چرخه‬

2. • Biological rhythm:
Circadian rhythm
Menstrual rhythm

3. Time stimulus like dark/light ,temperature
are zeitgeber.
They organize circadian rhythm.

4. There are two sleep drives, one homeostatic and
the other circadian.
The homeostatic drive increases with the
duration of wakefulness, whereas the circadian
signals are controlled by the suprachiasmatic
nucleus of the hypothalamus.
Recent evidence has shown that neurons of the
ventrolateral preoptic nucleus of the
hypothalamus are sleep active and sleep
promoting, confirming old observations that
lesions in this area induce insomnia.

5. These neurons express the inhibitory transmitters, galanin and GABA,
and innervate wake-promoting areas ,including:
The hypocretin (also known as orexin) containing neurons of the
posterolateral hypothalamus,
histaminergic neurons of the tuberomammillary nucleus,
the serotonergic dorsal raphe,
norepinephrine containing neurons of the locus ceruleus, and
the cholinergic neurons of the dorsal midbrain and pons.
In turn, monoaminergic wake-promoting areas inhibit the ventrolateral
preoptic nucleus, thereby resulting in reciprocal inhibition that self-
reinforces

8. Orexin
Orexin is subject both to circadian and homeostatic
regulation as the ablation of the suprachiasmatic
nucleus abolishes its production, while its levels are
enhanced by sleep deprivation .
Therefore, orexin seems to be an essential component of
the mechanisms maintaining prolonged wakefulness and
opposing to homeostatic sleep propensity.

9. As for REM sleep it has been found that the
Tuberomammilary nucleus,
Locus ceruleus and
Raphe nuclei contain Orexin receptors
exerting an Inhibitory effect on REM sleep
Therefore the absence of excitatory
orexin input would augment the
strength of REM mechanisms, thus
facilitating more frequent transitions to

10. Circadian rhythms generated by the central pace-maker in
the suprachiasmatic nucleus (SCN) control the timing
of wake and REM sleep , perhaps in part via projections
to orexin neurons that then relay this information to
sleep-regulatory and wake-regulatory regions .
It has been hypothesized that daytime sleepiness and
fragmented sleep of human narcolepsy could be
caused by impaired circadian control since circadian
signals help time and consolidate sleep-wake behavior .

13. Oscillatory EEG patterns arise because of
pacemaker cells, in which membrane
voltage fluctuates spontaneously, or
because of the reciprocal interaction of
excitatory and inhibitory neurons in circuit
loops.
The human EEG shows activity over the
range of 1 to 30 Hz, with amplitudes in the
range of 20 to 300 µV.

14. thalamocortical connections are critical in
the synchronization of electrical activity,
such as sleep spindles.

16. It has been estimated that each EEG
electrode “sees” the summed activity of
roughly 6 cm2 of underlying cortex.

17. These pathological waves of cortical
excitation and subsequent inhibition
affecting broad regions of excessively
synchronized cortex are thought to
underlie the spikes, sharp waves, and
sharp and slow wave complexes we
recognize as pathological correlates in
routine EEG interpretation.

18. Alpha rhythm
As with all repeating rhythms, it is most important to note the
frequency and the location of the activity, its amplitude, and its
reactivity. The alpha rhythm oscillation is between 8 and 12 Hz and
is most prominent over the more posterior aspects of the head. Its
amplitude or voltage in a bipolar (P4–O2) derivation is any-where
from 15 to 65 µV. This is reactive or responsive to mental activity
and to eye opening or closure. The rhythm is partially or completely
blocked by mental activity or by eye opening . Likewise, it is
enhanced by relaxation and by eye closure (Fig. 1). In a few healthy
subjects (<2%), no apparent alpha rhythm can be seen. in some
subjects (<7%), a very low-voltage alpha rhythm is observed.
Because recordings are bipolar, one can improve on alpha
detections by increasing the inter-electrode distances.

20. There may be a side-to-side amplitude
asymmetry, noted in approximately 60%
of people, in which the right side tends to
be of slightly higher amplitude.
The left side may be more predominant in
left handed individuals.
The difference in amplitude between the two
hemispheres is not more than 50%.

21. Beta activity (>12 Hz) is defined by three relatively
distinct frequency bands: 18 to 25 Hz activity,
which is the most frequently encountered; 14 to
17 Hz activity, which is less common; and the
still rarer, greater than 25 Hz activity. The first
two frequencies are seen commonly over the
frontal regions and become more prominent as
the subject gets drowsy. These two beta
rhythms are usually of low voltage (<25 µV). It
can be markedly increased by the use of some
drugs, most notably the benzodiazepines and
barbiturates. However, in those

22. Mu Rhythm
The mu rhythm is a centrally located rhythm
with a frequency of 8 to 10 Hz. It is
thought to be the resting rhythm of the
pre- and post-Rolandic cortex.

23. Theta
• Theta activity is defined as activity between 4 and 7 Hz.
Although theta activity is often a sign of disease or of
sleep onset, it may also be seen as part of a normal
awake EEG. Although some intermittent low-voltage
theta activity is seen over the frontal–central regions in
healthy people while resting and awake, this is usually
not a well-developed nor regular rhythm. Under a
circumstance in which the subject is performing some
moderately difficult mental task, such as spelling or
mathematics, one can occasionally see a well-developed
theta rhythm in the frontal midline region . A small
amount of left temporal theta activity during wakefulness
is also expected as a normal factor in aging, starting
around the age of 50 yr .

24. Lambda wave
• These waves may be quite asymmetric,They
will then have the patient close their eyes,
whichwill block the normal lambda wave but
usually not have an effect on the abnormal
activity.They will then have them open their eyes
and look at a plain piece of paper, which also
blocksthe normal lambda wave but will not effect
the epileptiform discharges, which are most
oftenmistaken for a lambda wave (3).

25. lamda

26. Stage I
The first suggestion that a patient is going
to sleep is that there is a sudden drop in
the voltage of their background alpha
rhythm, followed by intermittent theta
activity noted over the more posterior
head regions (Fig. 4). This presleep or
twilight state is usually followed by early
Stage II.

27. STAGE II
This stage’s onset is identified by the appearance of
spindles. They are frontal–centrally predominant waves
that occur as a cluster lasting for one to several seconds
in duration. The spindle frequency is between 11 and 15
Hz and, in healthy adults, they are bilateral and
synchronous in their appearance, with an amplitude up
to 30 µV. Spindles may appear by themselves or
following a vertex wave. In that latter situation, the wave
is called a “K complex”.
During the progression into deeper aspects of Stage II, the
background rhythm continues to slow into the slower
theta ranges, and high voltage generalized and frontally
predominant delta slow waves are noted (<4 Hz).

29. STAGE III
Occasionally a patient may go on to Stage III
sleep. In this phase, there are still vertex waves,
spindles, and K-complexes, but they occur less
frequently and seem to be over-whelmed by the
more prominent delta wave activity (<4 Hz). This
slow wave activity is widespread but has a
frontal and central predominance. It should be
the most frequently noted rhythm and should be
present for 20 to 50% of the record .
Stage III and the later Stage IV of sleep are most
often associated with increases in the interictal
discharges of temporal lobe epilepsy.

30. Stage III

31. STAGE IV
Stage IV also has rudimentary vertex
waves, spindles, and K-complexes, but
shows further slowing and a more
persistent delta-frequency background.
In this stage, most (>50%) of the time of
the recording is associated with
continuously appearing delta activity .
This stage is only rarely achieved in the
routine EEG recording.

33. REM
In sleep laboratories, the REM stage is divided into tonic
and phasic components based on the simultaneous
recording of other physiological parameters not routinely
monitored during EEG acquisitions .
The other recordings include respiration effort and pulse
oximetry, and chin and leg EMG activity.
From a strictly EEG perspective, the background rhythm
returns to what seems to be a drowsy or wakeful state,
with low-voltage theta and alpha frequency activity,
and with large, slow lateral eye movements .
This stage of sleep is also rarely encountered in routine
EEG.

34. • REM and NREM sleep differ physiologically.
• REM sleep is characterized by both phasic and tonic
changes in physiology. The drop in baseline EMG
correlates with a tonic change.
• Tonic physiological changes also include impaired
thermo regulation, reduction in ventilatory
chemosensitivity, hypotension, bradycardia, increased
cerebral blood flow, and intracranial pressure, increased
respiratory rate, and penile erection.
• Phasic changes include vasoconstriction, increased
blood pressure, tachycardia, and further increases in
cerebral blood flow and respiratory rate.
• During NREM sleep, the physiological state is more
stable, with an overall reduction in blood pressure, heart
rate, cardiac output, and respiratory rate. One
characteristic feature of NREM, slow-wave sleep is the
secretion of growth hormone.

35. narcolepsy

36. leptin
Reduced circulating leptin levels may be involved in the
pathogenesis of obesity in narcoleptic patients.
The fact that narcoleptic patients are obese in the face of
hypophagia suggests that they spend less energy, which
is supported by early observations.
Leptin is critically involved in the control of energy
expenditure and hypoleptinemia is associated with a
lower metabolic rate in obese animal models.
Alternatively ,hypocretin deficiency may reduce basal
metabolism directly via its inhibitory impact on the
sympathetic nervous system.

37. adenosine
It has been described that approximately 30% of Hcrt cells express A1
adenosine receptor. Adenosine is hypnogenic molecule that inhibits
wakefulness promoting neurons via a postsynaptic action mediated
through A1 adenosine receptor.
Caffeine is a xanthine derivative. The mechanism of action of caffeine
on wakefulness involves nonspecific adenosine receptor
antagonism. Adenosine is an endogenous sleep-promoting
substance with neuronal inhibitory effects.
In animals, sleep can be induced after administration of metabolically
stable adenosine analogues with adenosine A1 receptors (A1R) or
A2A receptors (A2AR) agonistic properties.
Adenosine content is increased in the basal forebrain after sleep
deprivation.
Adenosine has thus been proposed to be a sleep-inducing substance
accumulating in the brain during prolonged wakefulness .

38. • During slow wave sleep, activity of hcrt
neurons diminishes and results in
disinhibition of GABAergic neurons in the
ventrolateral preoptic area. During REM
sleep, hcrt neurons are silent and
disinhibit REM-on neurons in the
brainstem (16). In narcolepsy, the
absence of hypocretin neurons results in
lack of integration and coordination of
excitatory signals that modulate
wakefulness (17).

39. Sleep disorders
• Pseudoinsomnia
• Idiopathic insomnia
• Delayed sleep phase insomnia
• Drug insomnia
• Secondary insomnia
• Narcolepsia
• somnambolism

40. • Hypocretin neurons are activated by CRF in
response to stimuli that cause stress and this
activation may be responsible for the extended
arousal.
• stress is known to promote relapse of drug
seeking (21). Using an animal paradigm of
cocaine self-administration, we have shown that
a single injection of hypocretin can reinstate
cocaine seeking behavior in extinguished
animals (22).

41. • Among the regions innervated by the hypocretin neurons are the
ventral tegmental area(VTA), the locus ceorulus (LC), the prefrontal
cortex, the hippocampus, the nucleus accumbens, the amygdala,
the ventral pallidum and the TMN (14, 19, 20). Defined as the
mesocorticolimbic dopamine system, these neurons are related to
brain mechanisms of reward, reinforcement, and emotional arousal.
In accordance to this, we have inves-tigated whether the
hypocretinergic system has a role in the hyperaroused state that is
associated with stress and drug addiction. We hypothesized that
corticotrophin-releasing factor, a hormone that initiates the stress
response and activates the hypothalamo-pituitary-adrenal axis,
exerted an effect on hypocretin neurons. Indeed,CRF-containing
synaptic terminals contact hypocretin neurons and hypocretin
neurons express CRF receptors.