Formerly, Visiting Professor
of Clinical Neuropsychology, University of
Portsmouth; now at Bournemouth University,
UK
ABSTRACT
Yawning continues to pose as a
scientist's conundrum. Evidence is presented of
yawning and contagious yawning in a number of
different neurological disorders. Explanations
are discussed in the context of disparate
neurological disorders together with proposals
for how theses findings may be linked. Thus,
greater understanding of yawning and of
neurological disorders may be achieved by
exploring common neurochemical pathways and the
involvement of neurotransmitters that are
implicated in these different disorders.
Finally, contagious yawning is discussed in the
context of the susceptibility of persons and the
similarity this presents with our understanding
of the mechanisms involved in hypnosis.
Yawning is a primitive and misunderstood
mechanism that has attracted new interest in
recent years amongst academics and
neuroscientists alike. Yet it has been a
fascination of our early ancestral scientists
and philosophers. For example, Hippocrates
included it on his lists of useful "natures";
and in the ancient Hindu World, yawning was a
religious offence [1].
Yawning is a stereotyped response that is
seen in humans and animals from fish to mammals
[2]; in fact, in all classes of
vertebrates [3]. In preterm and near
term infants, yawn incidence significantly
decreases mainly during the day with a marked
decrease in yawn frequency with age probably
related to the development of circadian and
homeostatic control of sleep and wakefulness
[4]. In non-primates it has been related
to the rest-activity cycle with incidence higher
before than after the sleep episode
[5].
The most common theory of yawning is to
replace an oxygen deficiency in the blood.
Alternative theories are that stretching the
lungs leads to a feeling of being more awake
[6]. This is plausible since stretching
of these muscles involves special control
systems such as the locus coeruleus,
paraventricular nucleus of the hypothalamus, and
the reticular activating system.
Some researchers believe that our brains are
more efficient when they are cooler and
therefore a deep breath of fresh air can cool an
overheated brain. The contagious yawn may be an
innate action that recognises a particular
behavioural state as fifty per cent of us yawn
within five minutes of seeing another person
yawn. Even hearing a yawn may induce another
person to also yawn. Yet in children with autism
it is a very different situation. One study
showed that yawning faces triggered more than
twice as many yawns in non-autistic children
than in their counterparts [7].
Platek et al. [8] proposed that
contagious yawning is part of a more general
phenomenon known as mental state attribution
where people use their ability to inferentially
model the mental states of others. Therefore,
yawning may be associated with empathic aspects
of mental state attribution and are negatively
affected by increases in schizotypal personality
traits. Walusinksi [9] goes one step
further in suggesting that yawning shares the
neural networks involved in empathy. The
corollary of this is that we impart an
understanding of others through our observation
of their behaviour; more importantly, this
observation instils feelings and emotions in us
that are similar to those observed.
Cooper et al. [10] suggest that
minor neurons may be responsible during this
event since they not only fire when carrying out
an action but also during the observation of
that action carried out by another. Some
researchers advocate perception mechanisms as an
explanation for the yawn. For instance, Sarnecki
[11] suggests that higher level
representational states engage
neurophysiological structures in determining our
behaviour such as yawning.
Matikainen et al. [8] have suggested
that the movements and compressions caused by
yawning may affect the carotid body that is
strategically situated at the bifurcation of the
common carotid artery. Hence, yawning may
stimulate the carotid body which is highly
vascular and which will receive shunted blood
giving rise to an increase in pressure and
hormones release. Prasad [12] has
commented that the yawn may be a physiological
trait emerging from a vestigial reflex, similar
to the formation of goose bumps in humans under
stress, because at one time in evolutionary
history, the yawn served to coordinate the
aggressive social behaviour of a group of
animals.
Olivier Walusinski [13] has been
influential in re-writing our knowledge of the
"yawn". He coined the term "parakinesia
brachialis oscitans" [14] to describe
cases of hemiplegia where the onset of yawning
coincides with involuntary raising of the
paralysed arm. Furthermore, he has proposed that
mapping of the neural network for yawning may be
possible from knowledge of stroke localisation.
This invites an exciting new area of research
potentially linking together several
neurological disorders.
EXPLORING THE EVIDENCE
In rats, cholinesterase inhibitors such as
E2030 can induce yawning. Ogura and colleagues
[15] showed that Scopolamine, a
centrally acting anti-muscarinic drug,
completely inhibited E2030-induced yawning as
compared with the peripherally acting
Methylscopolamine [15]. Yet Scopolamine
did not block Donepezil Hydrochloride
E2020-induced yawning suggesting that central
cholinergic and dopaminergic mechanisms are to
some extent involved in E2030-induced
yawning.
There seems to be plenty of evidence of
repetitive yawning in various types of patients;
for example, Krantz et al.'s [16] case
report of repetitive yawning in a patient with
cardiac tamponade. Physiologically, yawning can
be divided into three distinctive phases: a long
inspiratory phase, a brief acme, and a rapid
expiration [17].
Gallup et al. [18] describe the case
histories of two women who suffer from chronic
and debilitating episodes of excessive yawning
in the absence of sleep problems. Both women
curiously showed signs of thermoregulatory
dysftmnction. Each also showed symptom relief
through means of behavioural cooling, thus the
authors suggest this demonstrates that recurrent
episodes of excessive yawning are not
necessarily related with a sleep disorder but
rather may be indicative of thermoregulatory
dysfunction.
It is known that brain temperature may rise
in patients with depression, and fall in
patients with mania [19]. Studies
revealed that yawning has many physiological
consequences that are consistent with those
required for the regulation of brain temperature
[20]. Also, the majority of therapeutic
strategies against mania are hypothermic, while
thermogenic strategies are used to combat
depressive disorders [21]. Therefore,
Prasad [21] proposes that drug induced
yawning serves as a compensatory brain cooling
mechanism when regulatory mechanisms fail to
operate favourably.
Examining the literature describing
different neurological disorders, such as
Multiple Sclerosis (MS), reveals that frequent
yawning may be associated with a number of
conditions. MS involves thermoregulatory
dysftmnction, with heat making symptoms worse
and cooling providing symptom relief
[22]. According to Gallup et al.
[23], increases in facial blood flow
resulting from a yawn operate like a radiator,
removing hyperthermic blood from the face and
head, while introducing cooler blood from the
lungs and extremities.
Provine et al. [24] found that
yawning tends to follow a circadian pattern
occurring most often before and after sleep.
People with MS very often experience problems
with sleep pattern [25]. Gallup et al.
[23] found that their MS patients indeed
experienced symptom relief when they were able
to nap during the day, which provided some
restoration and nourishment to their sleep
quotient.
Cattaneo et al. [26] have proposed
that excessive yawning may give rise to brain
stem ischaemia. They report two cases of brain
stem stroke involving the upper
pontomesencephalic junction in which excessive
pathological yawning was evidenced. In one
patient this was associated with gait ataxia and
in the other with upper limb and facial
hemiparesis. A causal relation is hypothesised
between the brain stem lesion and pathological
yawning. This is possibly related to denervation
hypersensitivity of a putative brain stem yawn
centre. Cattaneo et al. [27] suggest
that pathological yawning can be an early sign
of brain stem infarction.
For some time, researchers have suspected
that the brain stem is implicated in yawning.
However, in the past, researchers have
questioned whether the brain stem is solely
implicated in yawning [28] with others
reporting on findings involving brain stem
stroke and lesions in cortical and sub-cortical
areas. In particular, Singer et al. [29]
hypothesise that excessive yawning is a
consequence of lesions in cortical or
subcortical areas which pathologically control
diencephalic yawning centres despite not having
diencephalic lesions. Reporting on seven
patients with pathological yawning hyperthermic
blood from the face and head, while introducing
cooler blood from the lungs and
extremities.
Provine et al. [24] found that
yawning tends to follow a circadian pattern
occurring most often before and after sleep.
People with MS very often experience problems
with sleep pattern [25]. Gallup et al.
[23] found that their MS patients indeed
experienced symptom relief when they were able
to nap during the day, which provided some
restoration and nourishment to their sleep
quotient.
Cattaneo et al. [26] have proposed
that excessive yawning may give rise to brain
stem ischaemia. They report two cases of brain
stem stroke involving the upper
pontomesencephalic junction in which excessive
pathological yawning was evidenced. In one
patient this was associated with gait ataxia and
in the other with upper limb and facial
hemiparesis. A causal relation is hypothesised
between the brain stem lesion and pathological
yawning. This is possibly related to denervation
hypersensitivity of a putative brain stem yawn
centre. Cattaneo et al. [27] suggest
that pathological yawning can be an early sign
of brain stem infarction.
For some time, researchers have suspected
that the brain stem is implicated in yawning.
However, in the past, researchers have
questioned whether the brain stem is solely
implicated in yawning [28] with others
reporting on findings involving brain stem
stroke and lesions in cortical and sub-cortical
areas. In particular, Singer et al. [29]
hypothesise that excessive yawning is a
consequence of lesions in cortical or
subcortical areas which pathologically control
diencephalic yawning centres despite not having
diencephalic lesions. Reporting on seven
patients with pathological yawning caused by
acute middle artery stroke, they suggest that
pathological yawning also occurs in
supratentorial stroke.
Yawning despite trismus (the inability to
open the mouth which usually involves the
trigeminal nerve), has been reported in a
patient with locked-in syndrome caused by a
thrombosed megadolichobasilar artery
[30]. A vascular malformation of the
basilar artery-megadolichobasilar artery
(fusiform aneurysm, vertebrobasilar
dolichoectasia t) was determined to be the
underlying cause of this rare combination of
symptoms. A thrombus in the megadolichobasilaris
as well as an almost total pontine infarction
were demonstrated on CT- and MRT-scans. The
authors conclude that trismus may be associated
with locked-in syndrome due to
megadolichobasilar artery thrombus, although
yawning is still possible.
The suggestion that neocortical brain areas
have an inhibitory effect on the paraventricular
nucleus of the hypothalamus and that repetitive
yawning may be elicited because of liberation of
this area in some middle cerebral artery strokes
has also been hypothesised [30].
Walusinski [13] puts this succinctly
when he says that "yawning is an exterior
manifestation of the tonic stimulation of the
cortex by subcortical structures, particularly
when the brain stem does not receive appropriate
feedback from the cortex." (paragraph 6)
[30].
Gutiénez-Alvarez [31]
described two patients treated with Escitalopram
for more than 8 weeks for major depressive
disorder/generalised anxiety disorder. Ruling
out the possibilities of needing sleep or
effects related to sedation, the author found
that each patient developed excessive daytime
yawning. Curiously, their symptoms of yawning
disappeared on reduction of dosage rather than
on interruption and discontinuation. Therefore,
it is worth considering further the individual
effects of specific selective serotonin reuptake
inhibitors since their effects on excessive
yawning may be dose related.
Similarly, Propofol-induced yawning has also
been investigated with fluctuations in autonomic
function being noted [32]. However,
pre-treatment with Fentanyl may inhibit
Propofol-induced yawning.
DISCUSSION
We do not fully understand the origination
of yawning partly because there is a lack of
consensus of the specific and necessary (or
primary) neurotransmitters involved in yawning,
together with precise knowledge of all the
neurotransmitter pathways and their implication
in neurological disorders. The clinical and
neuro-chemical picture is of course fairly
sophisticated with considerable knowledge on the
subject in a number of sources ranging from
neuroscience, neuropsychology to neurology.
A good example of the complex yet revealing
nature of linking neurological disorders through
their neuro-chemical pathways has already been
seen with the initial lack of clarity of the
neurotransmitters thought to be involved in
Parkinson's disease (PD). Although the addition
of a dopamine receptor agonist such as
pergolide, ropinirole, pramipexole or
cabergoline to levo-dopa in patients with motor
complications reduces "off' time by about 1.1 to
1.5 hours per day [33], PD is now
commonly thought not to be the consequence of
solely dopamine depletion and irregularity.
PD is also associated with the additional
inegulation of serotonin. Depression is
frequently observed in PD and has been
associated with serotonin depletion. The
intraneuronal monoamine oxidase (MAO-A) is
active for dopamine, noradrenaline, and
serotonin. These have a paramount influence in
the pathogenesis of depression [34] and
are implicated in PD.
Important work emerging from the Laboratoire
de Médicine Expérimentale and
Clinique de Neurologie,
Pitié-Salpêtrière, France
[35] reveals that there are several
abnomialities in peptide content in Alzheimer's
disease (AD) and Huntington's chorea. The
authors suggest that whilst brain peptides
fulfil most of the criteria required of putative
neurotransmitters, it is not known whether they
act directly as rapid transmitters of impulse
traffic across the synaptic cleft or more
generally as modulators of neuronal
activity.
This doubt in neurotransmitter frmnction
together with multiple implications in chemical
pathways provides us with a complicated picture
that is not dissimilar to the perplexing
phenomenon of the clinical signature of AD in
people with co-morbid Down's syndrome
[36]. Possession of AD and Down's
syndrome does not categorically signal clinical
symptoms in later life [37].
The picture is no less complicated when
considering the effect of acetylcholine esterase
inhibitors such as Aricept (Donepezil
Hydrochoride, E2020) on memory functioning
[38], though perhaps the development of
vascular dementia from stroke may provide us
with more insight into the link between
neurological disorders through our understanding
of neuro-chemical pathways in these conditions
[39].
Yet researchers are generally united in
thinking that the yawning experience implicates
specific neurotransmitters including dopamine
(thought to activate oxytocin production in the
hypothalamus and hippocampus), acetylcholine
(known to be actively involved in memory
functioning), serotonin (considered important in
the feeling of well-being and pleasure), gamma
amino butyric acid (GABA), adrenocorticotrophic
hormone (ACTH), sexual hormones,
alpha-melanocyte stimulating homione (a-MSH),
and perhaps many others.
Schürmann et al.'s [40]
subjects' self-reported tendency to yawn
covaried negatively with activation of the left
periamygdalar region, suggesting a connection
between yawn contagiousness and amygdalar
activation. However, compelling evidence remains
from a variety of sources that implicate the
brain stem. Walusinski's "parakinesia brachialis
oscitans" [14] has been further
evidenced in two patients following brain stem
stroke [41].
The rare movement disorder described in some
cases of hemiplegia, was seen in a 39year-old
man and a 55-year-old man. Munhoz et al.
[41] described one of his patients as
having systemic arterial hypertension, sudden
dysarthria , dysphagia, dysesthesia and
incoordination in the left lower limb. When
yawning, his left upper and lower limbs had
spasm associated to the involuntary elevation of
the limb. Brain MRI showed an infarct in the
right pontine area.
Munhoz et al.'s [41] second case
presented with sudden vertigo when he turned his
head left, or when riding a bicycle, and was
followed by weakness and paresthesias of the
left lower limb. Brain MRI showed a small
infarct in the right side of the medulla
oblongata.
CONCLUSIONS
Whilst studies of stroke patients have
perhaps yielded the closest explanation and
localisation of the yawning experience, there is
scope in exploring normal subjects in terms of
whether an emotional component can explain
better the fact that yawning is so contagious
and that, on occasions, one person can elicit
yawning in another by simply talking about
it.
Walusinski [42] proposes that
yawning is a part of interoceptiveness by its
capacity to increase arousal and self-awareness.
If yawning connects consciousness as well as
unconscious interoception to higher mental
functions [43], then the suggestibility
involved in the act of yawning invites the
possibility of other neuro-chemical pathways
being implicated that may have their association
in the field of hypnosis.
Yawning represents an exciting challenge to
neuroscientists and neurologists. Although there
is a growing amount of literature on the topic
together with explanations that are not always
concordant, there remains a feeling amongst the
scientist fraternity that perhaps this is still
only the dawn of this science conundrum?
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H, Kosasa T, Kuriya Y, Yamanishi Y: Central
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