Yawning has been proposed to serve both
physiological and social functions, the latter
likely to have developed later in its evolution.
A central hypothesis is that yawning cools the
brain but whether yawning is a thermoregulatory
mechanism that is activated during hyperthermia
(i.e., thermoregulatory failure) or is activated
in any instance of brain temperature increase
(e.g., also during fever) is unclear and
experimental assessments of yawning during fever
are lacking. In this study, we determined the
effect of experimentally induced fever on
yawning frequency.
We also explored alternative predictors of
yawning during sickness (sleepiness, autonomic
nervous system indexes and sickness symptoms).
Twenty-two healthy human subjects participated
in a randomized, placebo-controlled, cross-over
study, where the subjects received an injection
of the bacterial endotoxin lipopolysaccharide
(LPS) at a dose of 2 ng/kg body weight in one
condition and placebo in the other. Yawning was
scored from video recordings from 30 minutes
before to 4h after the injection.
Body temperature was measured frequently,
alongside with heart rate, blood pressure,
nausea and overall sickness symptoms. Yawning
frequency was found to significantly increase
over time during experimentally induced
sickness, but not in the placebo condition. In
particular, yawning frequency was increased
during the rising phase of body temperature
induced by LPS administration, although no
significant correlation was found between body
temperature increase and yawning frequency.
In addition, exploratory analyses showed
that a higher yawning frequency was associated
with less increase in sickness symptoms and
nausea intensity. While the current study adds
to previous research showing significant
increase in yawning frequency during
hyperthermia, further studies are needed if we
are to properly characterize the brain cooling
role of yawning in humans. The investigation of
other functions, such as being a vasovagal
inhibitory, may shed stronger light on the
functions of yawning.
Résumé
Le bâillement pourait avoir à
la fois les fonctions physiologiques et
sociales, cette dernière susceptible
d'être apparue plus tard au cours de
l'évolution. Une hypothèse propose
que le bâillement réduirait la
température du cerveau, mais les
études des mécanismes du
déclenchement de cette activité
thermorégulatrice pendant l'hyperthermie
(c.-à-d. l'échec de la
thermorégulation), ou ceux qui seraient
activés dans tous les cas d'augmentation
de la température du cerveau, font
défaut.
Dans cette étude, les auteurs ont
déterminé l'effet d'une
fièvre expérimentalement induite
sur la fréquence des
bâillements.
Ils ont également exploré
d'autres prédicteurs du bâillement
pendant la maladie (somnolence, index du
système nerveux autonome,
nausées/vomissements). Vingt-deux sujets
en bonne santé ont participé
à une étude croisée
randomisée, contrôlée par
placebo, où les sujets ont reçu
une injection de lipopolysaccharide (LPS)
d'endotoxine bactérienne à une
dose de 2 ng / kg de poids corporel dans un cas
et un placebo dans l'autre.
Le bâillement a été
identifié à partir
d'enregistrements vidéo de 30 minutes
avant et 4 heures après l'injection. La
température corporelle a
été mesurée
fréquemment, ainsi que la
fréquence cardiaque, la tension
artérielle, la sensation nauséeuse
et ses symptômes généraux de
maladie.
La fréquence des bâillements
s'est révélée augmenter
significativement avec le temps au cours de
lapathologie expérimentale, mais pas en
condition de placebo. En particulier, la
fréquence des bâillements a
été augmentée pendant la
phase ascendante de la température
corporelle induite par l'administration de LPS,
bien qu'aucune corrélation significative
n'ait été trouvée entre
l'augmentation de la température
corporelle et la fréquence des
bâillements.
De plus, les études ont montré
qu'une fréquence plus
élevée des bâillements
était associée à une
augmentation moindre des symptômes de
maladie et de l'intensité des
nausées. Bien que l'étude actuelle
ajoute à la recherche
précédente montrant une
augmentation significative de la
fréquence du bâillement au cours de
l'hyperthermie, d'autres études seront
nécessaires afin de déterminer le
rôle de refroidissement du cerveau par le
bâillement chez l'homme. L'étude
d'autres fonctions, comme une inhibition
vasovagale, pourrait aider à comprendre
les fonctions du bâillement.
1. Introduction
Yawning is a common phenomenon, which can be
observed in humans as early as the 11th
gestational week and carries on throughout the
entire life span [1]. Striking
similarities across species indicate that
yawning is an evolutionary conserved behavior,
with strongly preserved features
[2&endash;4].
While contagious yawning can be triggered in
humans by seeing, reading about or hearing
someone yawn [5,6], spontaneous yawns
have often been associated with sleepiness and
boredom [7&endash;9], without any clear
consensus on its exact role. It seems reasonable
that yawning originated as a physiological
behavior and later evolved to also function as a
social signal, synchronizing behaviors such as
sleeping and hunting [10]. While it has
been suggested that yawning could help increase
arousal [11], another theory explaining
its physiological function proposes that it
would serve to cool the brain
[12&endash;15]. The two theories are
complementary as cooling the brain would also
favor arousal [4]. More specifically,
yawning has been proposed to cool the brain by
increasing the blood flow to the brain
[11,16], which is one mechanism to
reduce brain temperature [17,18]. This
increased circulation is caused by stretching
the jaw muscles and the contraction of the
lateral pterygoid muscles, which were suggested
to function as a pump squeezing blood from the
associated capillary plexus to the brain
[11,16,19]. The deep inspiration is also
believed to cause the cerebrospinal fluid to
descend and the blood flow in the internal
jugular vein to increase [20] as well as
to simulate heat exchange between venous blood
and cooler ambient air [21].
There are several experiments supporting the
brain cooling hypothesis of yawning. It has been
shown that people yawn less in a cold
environment (1.4°C) than in a warmer
environment (19.4°C) [13,22]. In
addition, putting a cold towel on the forehead
significantly decreased the frequency of yawning
of healthy participants in room temperature
[12]. Furthermore, rodent studies have
shown that intracranial temperature is increased
just before and is decreased just after a yawn
[23,24]. Altogether, there is strong
support for the braincooling hypothesis of
yawning [14,25,26]]. This
thermoregulatory hypothesis of yawning proposes
that yawning is triggered during hyperthermia
(i.e., when body temperature exceeds the body
temperature set point) to diminish brain
temperature [25,26]. This notion is
supported by studies indicating a reduced
yawning frequency when ambient temperature
approaches or exceeds 37°C, for instance
during summer in humans [22,27], when
braincooling mechanisms of yawning would become
less efficient. Accordingly, it has been
suggested that yawning would be suppressed
during fever as fever represents an increase in
the body temperature set point and is associated
with activation of heating thermoregulatory
mechanisms (e.g., shivering) while cooling
mechanisms are inhibited [14,28].
However, another function of yawning might be to
specifically protect the brain from excessive
temperature elevation [29]. This would
be particularly important during fever, when the
increase in body temperature is essential to
fight off pathogenic invaders, but when a
simultaneous increase in brain temperature could
jeopardize proper brain functioning
[30&endash;33]. For example, brain
hyperthermia can cause heat stroke and damage
brain cells [34&endash;36]. While it
remains unclear whether yawning is triggered or
suppressed during fever, we suggest that, if the
brain cooling role of yawning would be to
protect the brain from excessive temperature
elevation, increased yawning frequency in any
instance of increased body temperature, i.e.,
hyperthermia and fever, would be a significant
argument in favor of its brain cooling role. The
main aim of the present study was to determine
whether an experimental rise in body
temperature, induced by utilizing an acute human
sickness-model, would relate to an increase in
yawning frequency. Experimentally induced
sickness was obtained by intravenous injection
of lipopolysaccharide (LPS), an endotoxin that
activates the immune system and induces an acute
sickness response, including fever
[37&endash;39]. Yawning was scored from
video recordings of the subjects from 30 minutes
before to 4h after LPS administration, in
comparison to placebo administration. A
secondary and exploratory aim was to assess
other potential predictors of the increase in
yawning frequency during sickness, such as
sleepiness [8,9,11,38,40], changes in
autonomic nervous function and vagal activity
(i.e., blood pressure, heart rate, nausea)
[41&endash;43] and overall sickness
symptoms [43&endash;45]. In particular,
we hypothesized that sleepiness increases during
sickness would be associated with increased
yawning frequency, according to the suggested
role of yawning in increasing arousal
[11]. No specific hypothesis was defined
a priori regarding autonomic nervous function,
vagal activity and sickness symptoms, but these
variables were selected for their central role
in the sickness response.
4. Discussion
In the current study, yawning frequency
increased during the rising phase of temperature
in a protocol of experimentally induced
sickness. This is in line with the theory that
yawning acts as a thermoregulatory mechanism to
cool the brain [12]. According to this
theory, yawning is increased during hyperthermia
to diminish brain temperature [25,26].
In addition, while it was previously suggested
that yawning would be suppressed during fever,
which represents an adaptive elevation of the
body temperature set point rather than a
thermoregulatory failure [14,28], we
postulated that a specific blood cooling effect
of yawning might rather have a crucial role
during fever, when body temperature is essential
to fight off pathogens but when brain
hyperthermia could be detrimental for the
infected individual [34&endash;36]. The
current study is the first to use an
experimental model to induce fever and assess
related yawning frequency. Importantly, the
substantial increase in body/tympanic
temperature (average increase: 2°C)
occurred simultaneously with high yawning
frequency (average: 4 yawns/30min, maximum: 11),
which suggests that the increase in body/brain
temperature could serve as a triggering signal
for yawns. Although the data did not confirm the
hypothesized correlation between an increase in
body temperature and higher yawning frequency,
this may be due to the fact that a tympanic
thermometer does not necessarily reflect brain
temperature [54], and that the sample
size was limited. The design of the current
study allowed the testing of the hypothesized
differences in yawning frequency during
experimental fever in comparison to a placebo
condition, something that the data
supported.
However, contrary to our hypothesis, yawning
frequency was not increased during the peak
phase of body temperature (between three and
four hours after the LPS injection). This could
be due to increased sleep in sick participants
as we did not prevent the subjects from falling
asleep and there was a lot of free time and
possibility to sleep during this period. During
the second and third hours of the study day,
frequent questionnaires and tests were
administered, which prevented the subjects from
falling asleep.
Nevertheless, the presence of specific brain
cooling mechanisms in humans remains highly
debated [55&endash;57] and it is
possible that yawning may have served important
brain cooling properties at earlier stages in
evolution, but that its physiological role is
limited in modern humans. The human brain has
evolved with a number of effective mechanisms to
modulate arterial blood temperature, which
likely participates in the homeostasis of brain
temperature [58].
While yawning is a stereotypic behavior
enhancing blood flow to the skull, it could have
evolved into a social signal in humans
[15,59,60]. While the current study adds
to previous research showing significant
increase in yawning frequency during
hyperthermia in humans [13,61],
including social forms of yawning (i.e.,
contagious yawning) [12,22], further
studies are welcomed to properly characterize
the brain cooling role of yawning in humans,
notably by voluntarily modulating yawning
frequency during experimentally induced fever.
In addition, besides yawning frequency, yawning
duration should be assessed in further
investigations as it may provide additional
information [62].
The second and exploratory aim of the
current study was to assess other potential
indices associated with yawning frequency during
sickness. The fact that the increase in yawning
occurred during the peak of sickness symptoms
(see [46]) suggests that yawning could
have a role in sickness and would have an
adaptive component. Nausea intensity and
sickness symptoms were found to predict yawning
frequency after LPS administration. In
particular, more intense nausea and even more so
stronger sickness symptoms were associated with
lower yawning frequency after LPS
administration. This result was somewhat
unexpected, given that previous studies have
shown that nausea (e.g., during motion sickness)
usually leads to an increase in yawning
frequency [42]. Since nausea is
indicative of vagal nerve activation
[63], and that one major pathway for the
development of sickness symptoms during immune
activation is through activation of the vagal
nerve [64], our results may be explained
by the fact that yawning serves as an inhibitory
mechanism of the sickness-induced vagal
activation, possibly through deep and held lung
inflations. During inspiration, lung inflations
activate the slowly adapting pulmonary stretch
receptors (SARs), which serve as a feedback
mechanism to start the expiration: the SARs
project in the nucleus tractus solitarius (NTS),
to the GABAergic inhibitory neurons, which
inhibit the respiratory afferent signal
[65,66]. These inhibitory neurons may
possibly spread to other afferent branches of
the vagal nerve in the NTS as well, and thus
decrease nausea. This could explain the fact
that deep breaths decrease nausea
[67,68]. This may also be the reason for
which increased yawning is observed before a
vasovagal syncope [69], or why yawning
is seen to increase in subjects suffering from
motion sickness [42], as yawning would
serve as an inhibitory feedback mechanism.
However, the vasovagal inhibitory function of
yawning is only a speculative assumption here
and the study design used here does not allow to
conclude for a causative relationship. Studies
assessing specifically this mechanism should
therefore be performed. Comparison between
yawning and deep breaths in their
vago-inhibitory potential should also be
assessed, as yawning may induce larger and
longer lung inflations that may have more
benefits than deep breaths [70]. In
addition, other specific yawning-induced
mechanisms, such as increased cerebral blood
flow, could also improve sickness
symptoms/nausea [71]. Nevertheless, the
current study highlights a potential new role of
yawning during sickness, which should be further
investigated. Interestingly, a previous study
already documented a potential role of yawning
in relieving some malaise feeling in multiple
sclerosis [72].
One prevailing hypothesis of yawning is its
role to stimulate arousal when individuals
become sleepy [11]. We had therefore
hypothesized that higher yawning frequency could
be associated with stronger sleep drives.
Surprisingly, however, no association was found
between yawning frequency and sleepiness. This
result does not necessarily contradict the
arousal hypothesis of yawning but may merely
result from the fact that sleepiness might not
have been recorded with sufficient frequency, as
it was only recorded once and three hours after
the LPS injection. A higher frequency would be
needed to analyze whether yawning influence the
development of sleepiness across time during
sickness.
A number of other factors that could have
impacted the results were not measured in the
current study. For instance, some subjects were
exposed to more arousing situations than others,
such as pain during the drawing of blood, which
could have altered their yawning behavior.
Moreover, the behavior of the subject can be
influenced by the caregiver's behavior, for
example through contagious yawning
[5,73,74]. However, social presence
appears to instead reduce yawn frequency
[75], suggesting that the effects
observed in the current study are robust. In
addition, a relative small number of subjects
was included in the current study, which reduces
statistical power for the analyses based on
between subjects variation. However, this
experiment was performed in a within-subject
crossover design, using a high dose of LPS,
which allowed a reasonable power to draw
conclusions about the main effects of sickness
and body temperature.
In conclusion, we were able to show a clear
increase in yawning frequency during
experimentally induced sickness, which indicate
for a potential role of yawning during sickness.
The increase in yawning frequency occurred
during the rising phase of body temperature,
which adds to previous research showing
significant increase in yawning frequency during
hyperthermia. Our findings also bring
preliminary support for the hypothesis that
yawning serves to decrease sickness symptoms and
nausea through vagal inhibition. Studies
utilizing frequent samplings of sleep and
sleepiness are likely needed if we are to draw
conclusions about the role of yawning in
alertness in humans.
