See discussions, stats, and author profiles for this publication at: https://www.researchgate.

net/publication/344425939

Sleep-Wake Disorders: Definition, Contexts and Neural Correlations

Article · July 2019

CITATIONS READS

62 2,688

1 author:

Giulio Perrotta
Università Politecnica delle Marche
143 PUBLICATIONS 2,277 CITATIONS

SEE PROFILE

All content following this page was uploaded by Giulio Perrotta on 30 September 2020.

The user has requested enhancement of the downloaded file.

Avens Publishing Group
JInvi t ing Innova
Neurol t ions
Psychol
Open Access Review Article
July 2019 Vol.:7, Issue:1
© All rights are reserved by Perrotta G, et al. Journal
Avens of Group
Publishing

Neurology and
Invi t ing Innova t ions

Sleep-Wake Disorders: Definition, Psychology

Contexts and Neural Correlations Giulio Perrotta*
Department of Criminal and Investigative Psychology Studies, Italy
Keywords: Psychology; Neuroscience; Anxiety; Panic; Terror; Anxi-
*Address for Correspondence
ety disorders; Panic attack; Panic disorder; Nightmares; Sleepwalking;
Giulio Perrotta, Department of Criminal and Investigative Psychology
Sex in sleep; Nocturnal paralysis; Hallucinations; Nocturnal awakenings;
Studies, University of Federiciana, Cosenza, Italy, Phone: (+39) 349
Awakening; Narcolepsy; Hypersomnia; Amygdala; Prefrontal cortex; 21 08 872; E-mail: giuliosr1984@hotmail.it
Fear; Anxiety; Psychotherapy; Psychopharmacology; Benzodiazipines;
Antidepressants; Strategic approach Submission: May 23, 2019
Accepted: July 05, 2019
Abstract Published: July 08, 2019
Starting from the macro-category “sleep-wake disorders”, as Copyright: © 2019 Perrotta G, et al. This is an open access article
defined in DSM-V, the individual pathological conditions were defined, distributed under the Creative Commons Attribution License, which
permits unrestricted use, distribution, and reproduction in any medium,
focusing on the contextual and clinical aspects, to continue the
provided the original work is properly cited.
analysis on neural correlates and strategic therapy to be used to solve
the problems encountered.
for the proper functioning of both” [5].

Introduction Yet another definition indicates it as: “A readily reversible state of

reduced activity and interaction with the surrounding environment.”
Sleep: definition and contexts
Thus the term “readily reversible” cannot be associated with coma or
The sleep is defined as a state of rest opposed to waking. Various anesthesia which, respectively, are pathology and a pharmacologically
definitions indicate sleep as “a periodic suspension of the state of induced state of rest.
consciousness” [1,2], during which the body recovers energy; state of
Sleep therefore differs from other states of altered consciousness
physical and mental rest, characterized by the temporary detachment
of the conscience and the will, by the slowing down of the neuro a) With sleep the abolition of the state of vigilance is, as already
vegetative functions and by the partial interruption of the subject’s mentioned, reversible. Thus the subject can awaken after an even
sensorimotor relationships with the environment, indispensable for painless stimulus;
the restoration of the organism” [3]. Like waking, in fact, sleep is an b) Otherwise, stupor is an alteration of the state of consciousness
active physiological process that involves the interaction of multiple from which one can awaken only after administering a painful
components of the central and autonomic nervous system. In fact, stimulus;
although sleep is represented by an apparent state of rest, during this
state complex changes take place in the brain that cannot be explained c) The comatose state is an alteration of the state of consciousness
only as a simple state of physical and mental rest. For example, there from which one cannot awaken after administering a painful stimulus;
are some brain cells that at some stages of sleep have an activity 5-10 d) Brain death is much more serious with the irreversible
times greater than what they are awake [4]. cessation of all brain activity.
Two fundamental characteristics distinguish sleep from the Traditionally, three main measures have been used to define sleep
waking state: the first is that in sleep a perceptive barrier is created physiology:
between the conscious world and the external world, the second is
that a sensory stimulus of a certain level (for example a loud noise) a) The electroencephalogram (conventionally abbreviated as
can overcome this barrier and make the sleeping person wake up. “EEG”) which translates brain activity into electrical waves;

Proper sleep is biologically imperative for sustaining life. The b) The electrooculogram (conventionally abbreviated as “EOG”)
psychophysical health of the individual depends on the quality and records eye movements and translates them into electric waves;
duration of sleep. Sleep disorders, such as insomnia, are present c) The electromyogram (conventionally abbreviated as “EMG”)
in many psychiatric disorders, in which sleep deprivation has a which records muscular activity (usually in polysomnography that
significant impact on a person’s quality of life. of the mylohyoid muscle). For a thorough examination of sleep we
It is difficult to give a precise and unambiguous definition of use polysomnography, with which we record, during an entire night,
sleep. One of the mostaptis the one given in 1985 by Fagioli and a series of physiological parameters, such as the movement of the
Salzarulo, who present it as “a state of the organism characterized ribcage and the abdomen, the flow of air that passes through the
by reduced reactivity to environmental stimuli that involves a oronasal cavity, blood oxygen saturation and heart rate.
suspension of relational activity (relationships with the environment) In 1953, Eugene Aserinsky and Nathaniel Kleitman discovered
and modifications of the state of consciousness: it is established the presence of Rapid Eye Movements (REM) during sleep. This
autonomously and periodically, is self-limited in time and is simple observation made it possible to differentiate sleep in a REM
reversible “.Another well accepted definition efinesitas “a temporary phase (with rapid eye movements) and in a non-REM phase (NREM
and reversible detachment of the mind from the body, indispensable

Citation: Perrotta G. Sleep-Wake Disorders: Definition, Contexts and Neural Correlations. J Neurol Psychol. 2019; 7(1): 09.
Citation: Perrotta G. Sleep-Wake Disorders: Definition, Contexts and Neural Correlations. J Neurol Psychol. 2019; 7(1): 09.

ISSN: 2332-3469

characterized by sine waves of 8-12 Hz Alpha activity is typically

present and abundant when the subject is relaxed with eyes closed.
The activation pattern is present when the patient is in a state of
attention with open eyes. Eye movements are both rapid and slow
and muscle tone is medium to high.
During stage 1, the alpha activity decreases, the activation pattern
is poor and the EEG consists mainly of low-voltage waves of mixed
frequency between 3-7 Hz. The movements of the eyes are still
present but slow, rotating and oscillators (not in phase opposition
as in the REM phase). The electromyogram shows a persistent tonic
activity although of a lower intensity than the wake. In stage 2 there is
a relatively low background activity, with variable frequency but close
to theta waves (3-7 Hz). Stage 2 is characterized by the presence of
Figure 1: Hypnogram. two components, the so-called K complexes and the spindles of sleep
(or spindles). The latter of thalamic origin, lacking in lethal family
Source: https://www.researchgate.net/figure/Hypnogram-of-sleep-cycle-in-a-
healthy-young-adult-Normal-sleep-involves-cycling_fig1_267910844 insomnia, a deadly disease for sleep deprivation. The eye movements
are slow, while the EMG is further reduced. In stage 3, 20% - 50% of
phase). In 1963, Kleitman and Dement described for the first time each epoch (conventionally an EEG recording period of 30 s) must
the alternation, during the period of sleep, of REM and NREM contain Delta activities, i.e., large amplitude EEG waves (> 75 micro
sleep in cycles, introducing the concept of sleep architecture. At volts) and low frequency (about 0.5 - 4 Hz). The muscle tone in this
the end of the 1960s, after the discovery of REM and NREM sleep stage is slightly reduced and the eye movements practically absent.
and the concept of cyclical nature of these two phases within sleep, The spindles of sleep may or may not occur, while the K complexes
the need arose to classify the electroencephalographic changes are present, although they are often difficult to distinguish from delta
that occurred during sleep in a macroscopic manner in a standard waves. Stage 4 is characterized by the presence of delta waves, which
manner. In 1968, Rechtschaffen and Kales based on the analysis of here reach the maximum amplitude and minimum frequency, for
electroencephalographic, electromyographic and electrooculographic more than 50% of each era. As for stage 3, the spindles can be absent or
parameters classified sleep in 5 stages: 4 NREM stages (stage 1; stage present while the K complexes are present, but almost unrecognizable
2; stage 3; stage 4) and a REM stage (Figure 1). from the underlying delta rhythm. The movements of the eyes are
not present while a state of very low tonic muscle activation persists.
Sleep presents a regular alternation of non-REM and REM phases At this stage the metabolic activity of the brain is reduced (lower
consisting of cycles of similar duration to each other. After falling consumption of oxygen and glucose). If the subject wakes up at this
asleep the subject progressively passes from stage 1 of non-REM sleep stage he can get confused for a few minutes (Figure 2-4).
to stage 2, after which he passes to stage 3 or stage 4 and then, between
70 and 90 minutes after falling asleep, the first phase of REM sleep The REM stage is characterized by a low voltage EEG with
occurs which lasts about 15 minutes. At the end of the first phase of mixed frequencies. The EEG of REM sleep is very reminiscent
REM sleep the first cycle ends, which lasts approximately 80 to 100 of that of stage 1 if not for the discharged characteristics of waves
minutes. with the characteristic ‘saw-tooth’ morphology. PGO (ponto-genic-
occipital) waves appear, the activity of the hippocampus becomes
After the first cycle, others of a rather constant duration follow synchronized with the appearance of theta waves. The stadium takes
one another, but where REM sleep tends to increase in duration at its name from rapid eye movements and the low tone of the mental
the expense of non-REM sleep, in particular stages 3 and 4 (deep
sleep) which become shorter. During the night, in the end, REM sleep
constitutes about 25% of the total sleep duration. It is possible that
there are waking moments between the various cycles. The period of
sleep is represented graphically by the hypnograms that illustrate the
succession of the phases of wakefulness and sleep in relation to time.
Today in place of the subdivision into four stages the nomenclature in
three phases (N1, N2 and N3) adopted by the American Academy of
Sleep Medicine in 2007 on the basis of the appearance and frequencies
of the EEG oscillations, in which phase N3 combines stages 3 and 4
both characterized by the same large slow waves, even if in different
percentages.
During the vigil, the EEG basically alternates between two
patterns. A pattern called “activation” (or desynchronized pattern)
characterized by low voltage waves (10-30 micro volts) and Figure 2: Sleepphisiology.
high frequency (16-25 Hz) and a second called “alpha activity”
Part I. Source: https://foreverfitscience.com/sleep/sleep-physiology/

J Neurol Psychol 7(1): 09 (2019) Page - 02

Citation: Perrotta G. Sleep-Wake Disorders: Definition, Contexts and Neural Correlations. J Neurol Psychol. 2019; 7(1): 09.

ISSN: 2332-3469

four and a half times compared to those who sleep regularly.

Sleep-Wake Disorders: Classification and Clinical
Contexts
When we talk about these disorders we refer to a wide range of
problems characterized by an alteration of the sleep-wake rhythm [6].
Those who present these disorders are unable to benefit from their
rest and perceive their sleep as insufficient or unsatisfactory in quality
and quantity, resulting in stress and discomfort during waking hours.
Due to the close connection between sleep quality and physical
and emotional health, even when a sleep disorder occurs occasionally
in a person, it should never be neglected. Sleep-related disorders are
accompanied by clinically significant distress or impairment in the
social, occupational or other important areas.
Sleep-wake disorders include the following sub-categories with
related symptoms
Insomnia disorder: predominant dissatisfaction with the
quantity or quality of sleep associated with difficulty in starting sleep
at bedtime, maintaining sleep, with frequent or prolonged awakenings
during the night and early morning awakening with difficulty go back
to sleep. For there to be a diagnosis of insomnia disorder the difficulty
of sleeping must occur at least 3 times a week and must persist for at
Figure 3: Sleepphisiology.
least three months despite adequate sleeping conditions.

Part II. Source: https://healthengine.com.au/info/sleep-physiology Hypersomnolence disorder: excessive sleepiness despite a main
sleep period of at least 7 hours, manifesting at least three times a week
muscles. Moreover, this phase is characteristic for the paralysis of for at least three months. It is accompanied by clinically significant
the muscles (to avoid mimicking dreams) and because it is the one distress or impairment in cognitive, social, occupational or other
in which dreams predominantly occur. The brain consumes oxygen important areas. It is not attributable to the effects of a substance
and glucose as if the subject were awake and engaged in intellectual (a substance of abuse, a drug) and the complaint of sleep inessis
activity. If you wake up in this phase you are perfectly oriented. not adequately explained by the coexistence of mental and clinical
This stage is also characterized by a more imprecise control of the disorders. It is not justified by another sleep disorder and does not
vegetative functions of the organism, in fact the arterial pressure occur exclusively during the course of another sleep disorder.
increases and undergoes sudden changes, the heart rate increases and Narcolepsy: It is characterized by recurrent periods of
extra systoles can appear, the respiratory frequency becomes more irrepressible bi-dream of sleeping, sleep attacks or naps that occur
irregular and the part is compromised thermo regulation. Penile
erection in men and genital changes in women may occur. REM sleep
tends to decrease with advancing age and reaches a peak at the age of
1 year and then decreases in favor of non-REM sleep.
Sleep deprivation was tested by Randy Gardner in 1965, a young
17-year-old student who stayed awake for 264 hours, or 11 days. On
the second day, his concentration diminished and subsequently lost
the ability to identify objects by touch. At the end of the third day
he experienced bad temper and disorientation. At the end of the
experiment it was difficult to concentrate, to remember recent events;
he became paranoid and began to hallucinate. On the eleventh day, the
medical personnel who kept him under control wrote: “Confusional
state and disorientation, sudden mood swings, irritability, speak with
a road sign believing him a man, hallucinations, temporary loss of
identity, difficulty in pronouncing tongue twisters, mumbles many
words, diminished reflexes, memory lapses, difficulty in focusing
objects, visual problems with too bright colors ... “. When we
sleep little, in fact, learning, memory, mood and quick reflexes are Figure 4: Sleepphisiology.
compromised. Several studies show that sleeping systematically less Part III. Source: https://www.slideshare.net/mabdelghani/physiology-of-
than six hours a night increases the risk of heart attack for well over sleep-and-eeg-for-undergraduates

J Neurol Psychol 7(1): 09 (2019) Page - 03

Citation: Perrotta G. Sleep-Wake Disorders: Definition, Contexts and Neural Correlations. J Neurol Psychol. 2019; 7(1): 09.

ISSN: 2332-3469

parasomnias represent a large and heterogeneous group of sleep

disorders that consist of “undesirable manifestations that accompany
sleep and that often seem aimed at achieving a goal. In some cases they
can cause trauma and disturb sleep (of the patient or of those around
him)”. The different forms of parasomnia are classified according to
their occurrence during the different phases of sleep:
• NREM sleeps parasomnias (arousal disorders). NREM sleep,
especially during the deep sleep for this reason, these manifestations
occurs more frequently within 1-2 hours of falling asleep. An episode
on average last few minutes but its duration can be very variable: from a
few seconds up to even 30 minutes. Usually, NREM sleep parasomnias
arise in childhood (probably two to the high representation of deep
sleep during this phase of life) and tend to shrink or disappear with
Figure 5: Sleepwaves. adulthood. There is often familiarity with such episodes, which can
Source:https://corrosion-doctors.org/Dreaming%20is%20Personal/Glossary. be triggered by certain factors such as sleep deprivation, irregular
htm sleep-wake cycles, fever, infections, alcohol, certain medications and
other sleep disorders including sleep apnea. Patient soften do not
on the same day. These episodes must have occurred at least three retain any memory of the episodes themselves, the clinical features
times a week in the last 3 months. In order for there to be a diagnosis of which can be very heterogeneous. We distinguish 3 different types
of narcolepsy, episodes of cataplexy must occur at least a few times of manifestations (which can also occur in the same subject) which,
a month, characterized by a sudden, brief and reversible episode of according to the most recent interpretations, represent a continuum
muscle weakness that occurs in conjunction with emotional stimuli, of the same phenomenon, with different degrees of complexity:
such as laughter, surprise, anger, joy or sadness.
a) Confusion awake up. Episodes of partial wakening not
Respiratory-related sleep disorders associated with walking or autonomic disorders (the child seems to
a) Obstructive sleep apnea / hypopnea: repeated episodes of be awake but confused, disoriented, sometimes aggressive, does not
obstruction of the upper airway (pharyngeal) during sleep that respond adequately to orders, can speak but not in an inconsistent
can manifest itself with nocturnal respiratory disorders or daytime way);
sleepiness, asthenia or non-restorative sleep despite sufficient b) Sleepwalking. Episodes characterized by more or less complex
opportunity to sleep and not explained by other mental disorder automatic behavior (like walking, eating, drinking, and leaving home
or medical condition. Furthermore it is necessary that there are ...);
polysomnographic evidences of 15 or more apnea and/or obstructive
hypopnea as per hour of sleep. c) Night terrors. Episodes of partial wakening, often with sudden
onset, with expression of terror, intense agitation, sweating, pallor,
b) Central sleep apnea: repeated episodes of apnea and hypopnea wheezing, tachycardia.
during sleep caused by a change in respiratory effort. These are
ventilation control disorders in which respiratory events occur with • Parasomnias usually associated with REM sleep
a periodic or intermittent pattern. This disorder is detectable when They are complex motor manifestations that occur during REM
polysomnographic evidences of 5 or more central apnea are present sleep:
per hour of sleep and when the disorder is not better explained by
another concomitant sleep disorder. a) Behavioral disorder in REM

c) Sleep-relatedhypoventilation: polysomnography shows REM sleep represents that phase of sleep, mostly represented in
episodes of decreased respiration associated with high levels of carbon the second part of the night, in which there is an almost complete
dioxide, in the absence of a concomitant sleep disorder. loss of tone of the voluntary musculature (“it is as if immobilized”)
and during which the more dreamlike activity occurs intense. The
Circadian disorders of the wake-sleep rhythm: sleep interruption behavioral disturbance in REM sleep (RBD) is characterized by
due to an alteration of the circadian system, to a misalignment of the the loss of physiological muscle a tony. For this reason, during the
endogenous circadian rhythm and the wake-sleep rhythm required episodes, which occur more frequently in the second part of the night,
by the physical conditions of an individual or imposed by social the patients present an excessive motor activity, often characterized
or work commitments. In these cases, sleep interruption leads to by abrupt behavior (such as screaming, punching and kicking), in
excessive sleepiness or insomnia or both. Sleep disturbance causes relation to the content of their dreams. In fact, patients often report
clinically significant distress or impairment in social, occupational or dreams with a negative content, which they “act” by performing
other important areas. violent actions, which can assume characteristics of aggressiveness,
Parasomnias: they are disorders characterized by abnormal for example towards the bed partner. These manifestations therefore
experiences and behaviors or physiological events that occur in entail a high risk of trauma both for the patient and for those close
association with sleep, specific stages of sleep or sleep-wake passages. to him. Their duration is usually between 2 and 10 minutes and the
According to the most recent classification of sleep disorders, frequency can be very varied: from weekly or monthly episodes to

J Neurol Psychol 7(1): 09 (2019) Page - 04

Citation: Perrotta G. Sleep-Wake Disorders: Definition, Contexts and Neural Correlations. J Neurol Psychol. 2019; 7(1): 09.

ISSN: 2332-3469

multi-night (4-5 / night). hallucinations, but they can also be auditory, tactile, gustatory or
olfactory. They may be associated with sleep paralysis and, like these,
b) Sleep paralysis
occur frequently in individuals without other sleep disorders or may
They consist in the inability to perform any voluntary motor be one of the symptoms of narcolepsy.
activity (one has the perception of being completely immobilized),
d) Sleep-related eating disorder (SRED).
although the subject is completely conscious. They can occur during
the phase of falling asleep (“hypnagogic paralysis”) or following an Consists of repeated episodes during sleep of compulsive food
awakening (“hypnopompic paralysis”). They can be accompanied or drink ingestion (even unusual or inedible); often the level of
by auditory or visual hallucinations and can last from a few seconds consciousness during the episodes appears to be null or partial, just as
to several minutes, often causing intense anxiety in the person who the patient on waking frequently does not retain any memory of what
lives them. They can be resolved spontaneously or following sensory happened. This form of parasomnias appears more frequent in the
stimulation. They can be favored by an irregular sleep-wake rhythm female sex and has an onset around the 20-30 years; familiarity with
and sleep deprivation. other NREM sleep parasomnias is common. SRED can be associated
with other sleep disorders (arousal disorders, restless legs syndrome,
c) Nightly nightly
sleep apnea, narcolepsy) and can be triggered by taking certain drugs
They consist of fearful dreams, with a negative content, often (benzodiazepines, zolpidem, lithium) or by abrupt withdrawal of
of long duration; these dreams frequently induce the awakening of alcohol intake. This syndrome must be distinguished from other
the subject that keeps a vivid memory of it. They are common in forms of eating behavior in sleep such as “Night Eating Syndrome”,
children or in patients with “post-traumatic stress disorder”. They characterized by hyperphagia (overeating) evening and night and / or
can be favored by fever or by the abrupt withdrawal of alcohol or anorexia (lack of appetite) morning and insomnia.
drugs that reduce REM sleep (amphetamines, some antidepressants
and benzodiazepines). These conditions, in fact, could lead to a sharp
The Neural Correlates in Sleep-Wake Disorders
and significant increase in the representation of REM sleep, favoring A first system that controls and maintains the waking state is
the occurrence of nightmares. represented by the aminergic nuclei of the brainstem [7], in particular
by the noradrenergic neurons of the locus coeruleus and by the
• Other parasomnias.
serotonergic neurons of the raphe nuclei, but it is assumed that the
a) Groaning (Catathrenia) substance dopaminergic neurons also play a role Black. These neurons
project diffusely to the cortex, the thalamus, the hypothalamus and
It consists of the emission of a monotonous vocalization during
the hippocampus. When the subject is alert, the discharge frequency
a prolonged exhalation associated with bradypnea (reduction of
of the neurons of these systems is maximum, is greatly reduced during
respiratory rate). It often arises at a young age (20-30 years). The
non-REM sleep and almost completely during REM sleep, suggesting
episodes, which last about 2-20 seconds, occur more frequently during
that they are systems involved in waking maintenance. These neurons
REM sleep (especially in the second half of the night). The cause still
can also undergo phenomena of self-inhibition that promote sleep.
appears to be unknown and, at present, there is no treatment. Cases
Conditions that stimulate activity promote wakefulness, but if these
have been described in association with sleep apnea and only a few
systems are inhibited, sleep is promoted. If, however, it seems true that
have been resolved with nocturnal ventilatory treatment. However,
the stimulation of the noradrenergic system stimulates and maintains
it is important to distinguish such manifestations from snoring
wakefulness, serotonin, while also stimulating wakefulness, favors,
episodes.
over time, the synthesis and release of substances that promote sleep
b) Exploding head syndrome and inhibit the cholinergic neurons of the forebrain basal, involved in
maintaining the vigil, thus playing an ambiguous role.
It is characterized by the perception of a sound often very intense,
similar to an explosion or an explosion, which occurs especially during A second system that promotes wakefulness is the cholinergic
the phase of falling asleep, often resulting in a sudden wakening. The neurons of the basal forebrain. These neurons project to the cortex,
perceived sound, although very violent, is never accompanied by activating it, to the hippocampus and amygdale, and, in addition to
pain, but sometimes it can be related to visual flashes. If the crises being awake; they are active during the REM phase, which are not very
are recurrent and the sound perceived is particularly intense, the active in the non-REM phase. They are inhibited by serotoninergic
patient will tend to fall asleep with fatigue for fear of a new attack. terminations originating from the raphe nuclei. The cholinergic
The syndrome affects mainly women around the age of 50 and can nuclei of the brainstem include the laterodorsal nucleus of the
be favored by stressful conditions. Currently there is no univocal pontine tegmentum and the peduncolo pontine tegmentum nucleus
explanation of these phenomena as well as an effective therapy (some which are made up of two populations of neurons. A first population
cases described have been treated with calcium channel blockers). is characterized by neurons active during REM sleep, which discharge
watery low frequency during wakefulness and non-REM sleep
c) Hypnagogical / Ipnopompical hallucinations.
and which project to the aminergic nuclei of the brainstem. The
Vivid experiences, similar to dreams, often with bizarre or second population consists of neurons whose discharge frequency
terrifying contents, which occur during sleep (“hypnagogic”) or is maximum during wakefulness and during REM sleep and which
after awakening (“hypnopompic”). During the attacks the fantastic project to the thalamus and hypothalamus, activating them. The
sensations can be mistaken for real. In most cases these are visual tuberomammillary nucleus contains Histaminergic hypothalamic

J Neurol Psychol 7(1): 09 (2019) Page - 05

Citation: Perrotta G. Sleep-Wake Disorders: Definition, Contexts and Neural Correlations. J Neurol Psychol. 2019; 7(1): 09.

ISSN: 2332-3469

neurons which project diffusely to almost the entire central nervous attentional processes and in maintaining arousal, through direct
system, promoting waking maintenance and are maximally active dopaminergic connections towards the striatum nucleus, the basal
in this phase. The inhibition of these neurons with antihistamine forebrain and the cortex (Lu et al., 2006). These dopaminergic
induces sleepiness. The posterolateral hypothalamus comprises a neurons show the highest level of activity during wakefulness and
small group of orexinergic neurons that maintain vigil and are also REM sleep, 33 while their discharge decreases during slow-wave sleep
involved in the regulation of food intake. They diffusely project to the (Lena et al., 2005; Maloney et al., 2002).
structures involved in the regulation of the sleep-wake cycle in the
4) Serotonin (5-HT). The waking state is also maintained by the
central nervous system.
neurons of other brain stem structures: the Dorsal Nucleus of the
Vigil is a behavioral state characterized by arousal and cortical Raphe (DR) and the Medial Nucleus of the Raphe (MR). The neurons
activation, manifested in a desynchronized EEG pattern. In humans of these structures use serotonin (5-HT) as a neurotransmitter
it is characterized by a beta-type rhythm (frequency: 15 - 30 Hz; and project towards many regions of the diencephalon, the limbic
amplitude: <20 µV) during active and alpha-type vigil (frequency: 8 - system and the neocortex. These structures reach their maximum
12 Hz; amplitude: < 50 µV) during a relaxed vigil (Figure 5). peak discharge during wakefulness, decrease their activation during
NREM sleep and are silent during REM sleep.
This behavioral state is supported by the interaction between
different brain regions and by different types of neuromedicators: 5) Acetylcholine (Ach). Ponto-mesencephalic cholinergic
structures, such as the nucleus of the Laterodorsal tegmentum
1) Glutamate (Glu). At the level of the brainstem, the Reticular
(LDT) and the nucleus of the Pedunculopontine Tegmentum
Formation (FR) is essential to maintain the typical activating
(PPT), play an important role in maintaining wakefulness, but also
characteristics of waking. The FR is part of the Ascending Activating
in REM sleep, facilitating arousal cortical and desynchronization.
System (ARAS) which through diffuse projections from the
Both structures, parallel to the neurons of the FR, project towards
brainstem reaches up to the cortex, causing desynchronization. The
the specific thalamus-cortical projection system, where they cause a
projections that depart from the neurons present in the oral part of
diffuse cortical activation (Jones, 1995; McCormick, 1992; Steriade et
the pontine and mesencephalic FR ascend towards the prosencephaly
al., 1990). In small part, these structures also project to the posterior
and the cortex, where they sustain a cortical bone through a dorsal
hypothalamus, to the basal pros encephalon and to the FR through the
pathway, towards the thalamus, and a ventral pathway, towards the
extra-thalamic pathway. The discharge activity of these cholinergic
hypothalamus and the fore brain basal (Lindsley et al., 1950; Starzl et
neurons of LDT and PPT is high during wakefulness, decreases
al., 1951). On the other hand, the neurons present in the caudal part of
during NREM sleep and increases again during REM sleep (elMansari
the pontine and bulbar FR facilitate the tone of the postural muscles
M. et al., 1989; Steriade et al., 1990). The discharge of this cholinergic
through their projections towards the motor neurons present in the
system occurs in association with states of cortical activation (Jones,
spinalcord (Jones, 2005). One of the neuromediators that is involved
2005; Steriade et al., 1990), but it is not related to behavioral arousal.
in projections from FR nuclei is probably Glutamate (Glu) (Jones,
In fact, it has been shown that the injection at the level of the ponto-
1995). The importance of glutamate in wakefulness is also underlined
mesencephalic tegmentum of Acetyl Choline Agonists (ACh), such
by the fact that most anesthetics (including those for inhalation
as carbachol, causes cortical activation accompanied by inhibition
and ketamine) attenuate glutamate-mediated neuro transmissions
of muscle tone (Jones, 2004b). According to this, ACh can act in
(Rudolph and Antkowiak, 2004).
different populations of target cells to promote cortical activation
2) Nore Pinephrine (NA). The Locus Coeruleus (LC) is another and inhibit muscle tone. In the thalamus, for example, ACh acts on
important structure for waking: its noradrenergic neurons stimulate nicotinic receptors (nAChRs) and muscarinic receptors (M1ACh
cortical activation and arousal through their diffuse projections to and M2ACh) to facilitate cortical activation (Curro et al., 1991;
the forebrain, the trunk of the brain and the spinalcord. The neurons McCormick, 1992); in fact, Ach activates the thalamus-cortical relais
of the LC, in fact, discharge every frequently during wakefulness nuclei through an excitatory action directed on the nAChRs and
(especially during active wakefulness), decrease their discharge M1ACh receptors and through an indirect facilitation: inhibitory
during slow-wave sleep and cease their activity during REM sleep action on the thalamic-reticular GABAergic neurons through the
(Aston-Jones and Bloom, 1981; McCarley and Hobson, 1975). The M2ACh receptors. Similarly, in the FR of the brain stem, ACh can
role of Nor Adrenaline (NA) is however ambivalent, as it depends act on different receptors to excite some neurons that are involved
on the type of receptor on which it is going to act; in general, α-1 it her in cortical activation or motor inhibition, and based on two
adrenergic receptors have an excitatory action (depolarization due behavioral states, the wake and REM sleep, which are similar to each
to the closure of potassium channels); on α-2 adrenergic receptors, other due to the desynchronization of the tracing, but differ in other
it has an inhibitory action (hyper polarization due to opening of aspects, such as the presence or absence of muscular tony. How can we
the potassium channels). Through its receptors, the NA selectively explain this phenomenon? Under normal conditions there is a certain
excites the other systems that are involved in waking and inhibits balance between the noradrenergic and cholinergic systems so that
those structures that support sleep, especially at the level of the basal the activation of both neuronal systems maintains the waking state,
prosencephalon and the preoptic area (Jones, 2005). characterized by activation of the motor system and cortical arousal.
REM sleep and loss of muscle tone occur when the noradrenergic
3) Dopamine (DA). At the most rostral level, in the mesencephalic
system is inactive, while cholinergic is active. This association became
region, the Substantia Nigra (SN), the ventral tegmental area (VTA)
evident in the 1970s in an animal model through the administration
and the ventral Periaqueductal Gray (vPAG) play a priority role in
of Acetyl Cholinesterase Inhibitors (AChE), used to strengthen the

J Neurol Psychol 7(1): 09 (2019) Page - 06

Citation: Perrotta G. Sleep-Wake Disorders: Definition, Contexts and Neural Correlations. J Neurol Psychol. 2019; 7(1): 09.

ISSN: 2332-3469

activity of Ach. When they were administered alone, AchE inhibitors to the hypothesis that orexin, besides being important for waking
stimulated wakefulness; conversely, when they were administered maintenance, is fundamental for the stabilization of the wake-sleep
following the removal of catecholamines (therefore also of NA), by switch (Saper et al., 2001).
administration of reserpine, they stimulated REM sleep (Curro et al.,
Melatonin: Contexts and Clinical Profiles
1991; Jones, 2004b; McCormick, 1992). In men, acetyl cholinesterase
inhibitors, when given during waking, stimulate cortical activation From a neurobiochemical point of view, as already stated [8],
and induce prolongation of waking state; while, they accelerate the the pineal gland produces melatonin, a hormone isolated for the first
onset of REM sleep when administered during NREM sleep, when time in 1958 by Aaron Lerner and produced by pinealocytes starting
the noradrenergic system and other arousal systems are inactive from the neurotransmitter serotonin (5-hydroxy-tryptamine) for
(Gillin and Sitaram, 1984). On a more rostra level, in the basal N-acetylation and oxy-methylation, by virtue of the fact that these
pros encephalon, there are other neural compartments that use cells contain the enzyme Hydroxyindole-O’xymethyltransferase
acetylcholine as a neuro mediator, such as the medial septum (MS (HIOMT), epiphysis marker enzyme.
/ vDB: medial septum / vertical limb of the diagonal band) and
It acts in the circadian rhythm of sleep and has powerful
other nuclei, which play a major role in cortical activation, receiving
antioxidant effects: melatonin is synthesized in the absence of
input from structures of the brainstem and the hypothalamus, and
light from the pineal gland; shortly after the onset of darkness, its
projecting diffusely towards the cortex (Jones, 2004a; Lee et al., 2005).
concentrations in the blood increase rapidly and reach the maximum
These neurons are very important in generating the theta rhythm (4 -
between 2 and 4 am and then gradually decrease as the morning
7 Hz) and gamma (30-60 Hz) during wakefulness and REM sleep. At
approaches.
this level there are also other GABAergic and glutamatergic neurons
that increase their discharge in association with corticalactivation Exposure to light (especially at the blue wave length between
(Gritti et al., 1997; Manns et al., 2003) and seem, above all the latter, 460 and 480 nm) inhibits the production of melatonin in a dose-
to be responsible for the increase in behavioral arousal and tone of dependent manner. It is therefore used for the short-term treatment
postural muscles (Gritti et al., 1994; Henny and Jones, 2006). of insomnia over 55 years of age.
6) Histamine (His). As already observed by von Economo (von The side effects of melatonin are not null, although the contrary
Economo, 1930), another important region for waking maintenance belief is widespread: over the years, various professional bodybuilders
is the hypothalamus. The back and side of this structure appears and various sports information magazines have affirmed the
to have a specific role in cortical activation. The neurons of the possibility, with the support of some scientific studies, that daily
tuberomammillary nuclei (TMN), forming part of the posterior doses between 0.5 mg and 3 mg, taken 30-60 minutes before training,
rhypothalamus, use histamine as mediator and stimulate, through increase the levels of growth hormone, without giving side effects,
diffuse projections, cortical activation (Brown et al., 2001b; Saper which are usually recognized in irritability and drowsiness.
et al., 2001). Histaminergic neurons discharge profusely during
Melatonin decreases the release of GnRH: for this reason the
wakefulness, decrease during NREM sleep and cease their activity
in REM sleep. Histamine has an excitatory effect on most of the synthesis of testosterone and therefore libido decreases. More
ARAS nuclei and, in contrast, inhibits the “sleep active” neurons of precisely, it inhibits the secretion of the luteinizing hormone, which
the Ventro Lateral Preoptic area (VLPO), by excitatory synapses on stimulates the male endocrine activity of the interstitial cells of the
inhibitory inter neurons (Liu et al., 2010). testis with testosterone and sperm production, and in the female
ovulation and conversion of the ovarian follicle into the corpus
7) Oressin / Hypocretin (Orx / Hcrt).Finally, at the level of the luteum. Taken for prolonged periods, melatonin can have a depressive
lateral hypothalamus (Lateral Hypothalamus, LH) there are neurons effect in predisposed subjects; furthermore, it can inhibit ovulation
that use a known peptide with the double word: oressin / hypocretinas precisely because of the suppression of the GnRH release it causes.
mediator. This plays a fundamental role in promoting and stabilizing
the waking state, while suppressing REM sleep. A deficiency of this Recent research in the biomedical field, especially on melatonin,
peptide leads to narcolepsy (Chemelli et al., 1999; Lin et al., 1999; has shown that:
Mignot et al., 2002; Peyron et al., 2000), ie a neurological disorder 1) Melatonin is importantly involved in inflammatory processes
characterized by daytime sleepiness accompanied by cataplexy and cellular apoptosis [9].
(sudden loss of muscle tone), hypnagogic hallucinations (auditory and
/ or visual hallucinations during the phases of sleep / wake or sleep) 2) Exposure to electromagnetic fields decreases the secretion of
and sleep paralysis (inability to move or speak during awakenings) melatonin [10], which negatively affects cellular processes linked to
(Yoss and Daly, 1957). Oressinergic neurons have connections with death, acts on sex hormones and connected glands and interferes
all the nodes that intervene in the wake-sleep cycle and are actively with the sleep-wake rhythm [11].
inhibited during the NREM sleep phase by the GABAergic neurons 3) Melatonin intervenes in the neurobiological processes involved
of the preoptic region and of the basal pros encephalon. These
in anorexic and bulimic disorders and in the predisposition to be
oressinergic nuclei maintain the vigil by a diffuse projection towards
subject to these psychophysical pathologies [12].
the aminergic systems, in particular towards the LC, where they
promote the vigilat the expense of REM sleep (Bourgin et al., 2000; 4) Melatonin is involved with cortisol in the immunomodulatory
Hagan et al., 1999). The anatomical distribution of the connections response [13].
of oressinergic neurons and their involvement in narcolepsy has led

J Neurol Psychol 7(1): 09 (2019) Page - 07

Citation: Perrotta G. Sleep-Wake Disorders: Definition, Contexts and Neural Correlations. J Neurol Psychol. 2019; 7(1): 09.

ISSN: 2332-3469

5) Melanin intervenes in the regulation of acidosis in malignant naps during the day.
tumor processes [14].
- Always follow the same ritual before going to bed, dedicating
6) Melatonin is a potent inhibitor of ovarian and prostate cancer yourself to relaxing activities.
[15,16].
- Perform physical activity during the day and not in the evening
7) Melatonin has positive effects on blood pressure, reducing hours.
hypertension [17].
- Take meals at regular times, preferring a light diet for dinner.
8) Melatonin, having antioxidant and modulating properties - Avoid the intake of exciting substances (tea, coffee, alcohol,
of the circadian rhythm, has positive effects on drug therapy in the nicotine) in the evening hours.
presence of schizophrenia and in general in psychotic syndromes
[18,19]. - Rest on a comfortable bed in a cool, dark room silent and well
ventilated.
9) Melatonin has a positive effect on blood sugar, reducing blood
levels and favoring a positive prognosis on insulinic therapy in the In the presence of a pathological disorder, however, the
rats [20]. intervention of a specialist in neurology or psychiatry is required to
carry out a targeted therapy consisting of pharmacological and/or
10) Melatonin, compared to problems related to the central psychotherapeutic treatment.
nervous system, seems to be directly involved in the reduction of
tissue and nerve lesions, affecting free radicals due to its powerful References
antioxidant effect. Since endogenous melatonin levels decrease 1. Giulio Perrotta (2019) Psicologia clinica. Lux-co Edn. Clin Psychol A5: 244.
significantly in senility, these result simply that the loss of this 2. Giorgio Coccagna, Il sonno e i suoi disturbi, Piccin-Nuova Libraria (2nd edn).
antioxidant could contribute to the incidence or severity of some age-
3. Sónno, in Treccani.it - Vocabolario Treccani on line, Istituto dell’Enciclopedia
related neurodegenerative diseases [21]. Italiana, 2011
11) Melatonin, precisely because it is related to serum and ionized 4. Ltd. Pan Macmillan. Macmillan dictionary for student’s pp. 1216.
calcium levels [22], positively intervenes in vertebral disorders 5. Hobson JA, Pace-Schott EF, Stickgold R (2000) Dreaming and the brain:
and intervertebral degeneration (in chicken) [23,24]; also in the Toward a cognitive neuroscience of conscious states. Behav Brain Sci 23:
cartilaginous problems and curvature of scoliosis [25,26]. 793-842.

6. Giulio Perrotta (2019) Psicologia clinica. Lux-co Edn. Clin Psychol A5: 244.
12) Melatonin has beneficial effects on respiratory problems
linked to obstructive bronchospasm [27]. 7. Imeri L, Mazzanti M (2013) Sonno e malattie neurodegenerative in modelli
animali. Tesi di Dottorato di Ricerca 1-239.
In recent decades [28,29], the integration of melatonin in the diet
8. Perrotta G (2019) The Pineal Gland: anatomical, clinical and neurobiochemical
has allowed a significant and positive management of primary sleep profiles, between hypotheses of the past, certainties of the present and future
disorders, especially at a dose of 2-10 mg, unlike the classic 0,5-1 mg perspectives. J Neurol Psychol 7: 1-5.
dose indicated for jet lag disorder. 9. Tarocco A, Caroccia N, Morciano G, Wieckowski MR, Ancora G, et al. (2019)
Melatonin as a master regulator of cell death and inflammation: molecular
Conclusion mechanisms and clinical implications for newborn care. Cell Death Dis 10:
317.
Sleep disorders represent a primitive alteration of its regulatory
mechanisms and therefore of the physiological rhythms of the sleep- 10. Pfluger DH, Minder CE (1996) Effects of exposure to 16.7 Hz magnetic fields
on urinary 6-hydroxymelatonin sulfate excretion of Swiss railway workers. J
wake cycle or be the clinical expression of other pathologies, organic Pineal Res 21: 91-100.
or psychic. Chronic sleep deprivation, altering the sleep-wake cycle
11. Halgamuge MN (2019) Pineal melatonin level disruption in humans due to
e all the associated biological rhythms, involves the exhaustion
electromagnetic fields and ICNIRP limits. Radiat Prot Dosimetry 154: 405-
of energy that feeds our life, compromising its quality in all its 416.
dimensions: personal, affective, family, socio-relational and working.
12. Liu L, Yi J, Ray WK, Vu LT, Helm RF, et al. (2019) Fasting differentially alters
Sleep is therefore a cornerstone of health. the hypothalamic proteome of chickens from lines with the propensity to be
anorexic or obese. Nutr Diabetes 9:13.
For this reason, morphological disorders must always be taken
seriously consideration and shared with your doctor to be able to 13. Baekelandt S, Mandiki SNM, Kestemont P (2019) Cortisol and melatonin
involved in the immune modulation by the light. J Pineal Res 29: e12573.
identify and therefore eliminate, where possible, any causes triggers,
through a targeted behavioral and / or intervention pharmacological. 14. Sonehara NM, Lacerda JZ, Jardim-Perassi BV, de Paula Jr R, Moschetta-
Pinheiro MG, et al. (2019) Melatonin regulates tumor aggressiveness under
The so-called “sleep hygiene”, which is achieved through the adoption
acidosis condition in breast cancer cell lines. Oncol Lett 17: 1635-1645.
of behaviors that aim to promote a good night’s sleep, already helps
improve sleep quality and maintain it over time, representing the 15. Zare H, Shafabakhsh R, Reiter RJ, Asemi Z (2019) Melatonin is a potential
inhibitor of ovarian cancer: molecular aspects. J Ovarian Res 12: 26.
primary strategy.
16. Hogan E, Almira-Suarez I, Li S, Collins SP, Jean WC (2019) Clinical
The basic advice, in the absence of diseases, to sleep properly are: management of prostate cancer metastasis to pineal gland: case report and
review of literature. World Neuro Surg 122: 464-468.
- Respect your own sleep-wake rhythm, lying down and waking
17. Hadi A, Ghaedi E, Moradi S, Pourmasoumi M, Ghavami A, et al. (2019)
up around the same time (even during the weekend) and avoiding

J Neurol Psychol 7(1): 09 (2019) Page - 08

Citation: Perrotta G. Sleep-Wake Disorders: Definition, Contexts and Neural Correlations. J Neurol Psychol. 2019; 7(1): 09.

ISSN: 2332-3469

Effects of melatonin supplementation on blood pressure: a systematic review intervertebral disc degeneration via the potential mechanisms of mitophagy
and meta-analysis of randomized controlled trials. Horm Metab Res 51: 157- induction and apoptosis inhibition. J Cell Mol Med 23: 2136-2148.
164.
23. Alini M, Eisenstein SM, Ito K, Little C, Kettler AA, et al. (2008) Are animal
18. Bastos MAV Jr, Oliveira Bastos PRH, Portella RB, Soares LFG, Conde RB, models useful for studying human disc disorders/degeneration? Eur Spine
et al. (2019) Pineal gland and schizophrenia: A systematic review and meta- J 17: 2-19.Turgut M, Başaloğlu HK, Yenisey C, Özsunar Y (2006) Surgical
analysis. Psychoneuroendocrinology 104: 100-114. pineal ectomy accelerates intervertebral disc degeneration process in
chicken. Eur Spine J 15: 605-612.
19. Takahashi T, Nakamura M, Sasabayashi D, Nishikawa Y, Takayanagi Y
(2018) Reduced pineal gland volume across the stages of schizophrenia. 24. Uyanikgil Y, Cetin Uyanikgil EO, Turgut M (2016) Effects of Melatonin upon
Schizophr Res 2016: 163-170. vascularity of cartilage end plate of intervertebral Disc. J Spine 5:e123.

20. Dantas-Ferreira RF, Raingard H, Dumont S, Schuster-Klein C, Guardiola- 25. Liu H, Liu Z, Chi-wai M, Guo J, Han X, et al. (2019) The effect of exogenous
Lemaitre B, et al. (2018) Melatonin potentiates the effects of metformin on melatonin on reducing coliotic curvature and improving bone quality in
glucose metabolism and food intake in high-fat-fed rats. Endocrinol Diabetes melatonin-deficient, C57BL/6J mice. Sci Rep 9: 6202.
Metab 1: e00039.
26. Tsai SC (2017) Chronic obstructive pulmonary disease and sleep related
21. Uyanikgil Y, Cavusoglu T, DoganKılıc K, Yigitturk G, Celik S (2017) Useful disorders. Curr Opin Pulm Med 23: 124-128.
effects of melatonin in peripheral nerve injury and development of the nervous
system. J Brachial Plex Peripher Nerve Inj 12: e1-e6. 27. Claustrat B, Leston J (2015) Melatonin: Physiological effects in humans.
Neurochirurgie 61: 77-84.
22. Chen Y, Wu Y, Shi H, Wang J, Zheng Z, et al. (2019) Melatonin ameliorates
28. Quera-Salva MA, Claustrat B (2018) Melatonin: physiological and
pharmacological aspects related to sleep: The interest of a prolonged-release
formulation (Circadin®) in insomnia. Encephale 44: 548-557.

J Neurol Psychol 7(1): 09 (2019) Page - 09

View publication stats