Yawning is a poorly understood
phenomenon which is observed in humans and a
wide variety of species (Lehmann, 1979). The
occurrence of yawning, often associated with
stretching, prior to falling asleep and upon
awakening and the observation that yawning is
associated with increased cortical EEG
activity indicate that it is a reliable
predictor of a change in arousal levels (Concu
et al.. 1974, Serra et al., 1986; Baenninger et
al., 1996). Experimental lesion studies indicate
that the striatum is critically involved in the
yawning process (Zarrindast et al., 1995a).
Apomorphine and other dopamine (DA) receptor
agonists administered to rats systemically or
directly into the caudate nucleus induce yawning
responses indicating that a central dopaminergic
system is involved in yawning behavior
(Mogilinicka and Klimek, 1977, Zarrindast et
al., 1995a, b). Pharmacologie studies indicate
that yawning is associated with increased DA
release coupled with activation of postsynaptic
DA-D2 receptors (Rollinson et al., 1979; Serra
et al., 1986, 1987). The DA-D2 receptors
mediating yawning appear to be functionally
linked to Dl receptors in such a way that
endogenous DA by stimulating Dl receptors plays
a permissive role for the expression of yawning
induced by postsynaptic DA-D2 agonists (Longoni
et al., 1987). The relationship between yawning
and the dopaminergic system is of particular
interest for Parkinson's disease (PD) since PD
is associated with decreased striatal
dopaminergic activity and also because the
disease is treated with levodopa or DA receptor
agonists which stimulate DA-D, receptors and
enhance striatal dopaminergic activity. Little
is known about the occurrence of yawning in
medicated PD patients although Goren and
Friedman (1998) recently reported a patient
treated with levodopa in whom yawning, often
associated with stretching, preceded the onset
of "on" periods. I recently encountered a
patient with juvenile onset PD in whom yawning
and stretching were observed during treatment
with AC pulsed electromagnetic fields (EMFs) of
picotesla flux density applied transcranially.
The patient was a 49 year old right handed
woman who was diagnosed with PD at the age of 38
after she developed micrographia and stiffness
of the right arm. She has been treated with
carbidopa-levodopa since the age of 40 and was
functioning well until about a year ago when she
began to experience worsening of her symptoms
with increasing tremor and stiffness of the
right arm and hand, increasing bradykinesia,
stiffness of the neck, debilitating fatigue, and
increasing depression and anxiety. At the time
of presentation in July of 1998 she was treated
with a sustained release carbidopa-levodopa
(Sinement CR, 25/100, 6 tabs/d),
carbidopa-levodopa (Sinement 25/'100, 3 tabs/d),
sertraline hydrochloride (Zoloft 100mg/d) and
ergoloid mesylaies (H\yergine 3mg/d). On
examination she exhibited masking of facial
expression, hypophonia, resting tremor and
rigidity in the right arni and hand, generalized
bradykinesia with shuffling gait, and
difficulties with balance and postural
stability. She also exhibited -on-off-
fluctuations in motor performance. "Off -
periods were associated with increasing
immobility and worsening of the tremor while
"on" periods, each lasting up to 2 hours were
associated with improved mobility and the
emergence of dystonic dyskinesias of the neck
and trunk. Due to a rather rapid deterioration
of her Parkinsonisin in the past several months
she elecied to undergo treatment with EMFs.
After obtaining an informed consent the
patient received daily (mid-morning), for 5
consecutive days, two successive treatments with
EMFs using the Sandyk Electromagnetic Stimulator
in a quiet and artificially illurninated room
that was magnetically unshielded. The
Electromagnetic Stimulator produced on AC pulsed
EMF of 7.5 picotesla flux density whichwas
applied transcranially via a set of 24 coils
placed over the patient's head. A 5 Hz
sinusoidal wave was used in the first treatment
of 15 minutes duration and following an interval
of 15 minutes during which time the device was
turned off, a second pulse of 7 Hz sinusoidal
wave was administered for 20 minutes. The
patient's eyes were shielded during the
applications of EMFs. Treatment with EMFs was
initiated each time during an -on" period about
20 - 30 minutes after the patient was medicated
with carbidopa-levodopa. Characteristically,
during the administration of the first treatment
this patient reported feeling relaxed and
towards the end of the treatment she felt
slightly drowsy. Usually within several minutes
after initiation of treatment she began to
yawn at a rate of about 1 - 2 yawns per
minute. The patient noted that the onset of
yawning coincided with a complete cessation of
the tremor and resolution of the rigidity in the
right arm and neck muscles. Episodes of yawning
continued throughout the duration of the first
treatment and also during the interval when the
magnetic stimulator was turned off. During
the second treatment she felt more awake and
alert, yawned more frequently (2 - 3
yawns/minute) and also exhibited stretching
movements of the arms and trunk some of
which were identical to those observed at night
prior to falling asleep or upon awakening from
physiological sleep. After the termination of
the second treatment she continued to yawn,
albeit less frequently, for about 10- 15
minutes. The patient could not recall yawning or
stretching in association with the use of
dopaminergic medications.
Yawning is considered an evolutionary vestige
of a behavior associated with changes in
activity and arousal levels (Anias et al., 1984:
Baenninger et al., 1996). The yawning reflex is
mediated through subcortical pathways which
reach no higlier than the basal ganglia.
Frequent yawning may occur with cerebral
disease. It may be an epileptiform phenomenon or
could occur as a sequela of encephalitis.
Paroxysms of' yawning may also be caused by
cerebral tumors, especially those located in the
posterior fossa, opiate withdrawal hypothalamic
disease, and as a complication of
electroconvulsive therapy and concurrent
neuroleptic withdrawal (Boshes, 1969; DeJong,
1979; D'Mello et al., 1988). Recurrent episodes
of yawning have also been observed in patients
with Tourette's syndrome and multiple sclerosis
during transcranial administration of AC pulsed
EMFs (Sandyk, l995 Sandyk, 1997).
Yawning is a DA mediated phenomenon although
it is regulated also by other neurotransmitters
and neuropeptides such as acetylcholine,
serotonin, adrenocorticotropic hormone (ACTH)
and melanocyte stimulating hormone (MSH), opioid
peptides, oxytocin, and luteinizing hormone
releasing hormone (LHRH) (Mogilnicka and
Kliniek, 1977; Rollinson et al., 1979, Yamada
and Furukawa, 1980, Bertolini and Gessa, l98l
Mora and Diaz-Veliz, 1989; Argiolas and Melis,
1998). For instance, serotonergic mechanisms may
have a facilitatory effect with respect to DA
receptor agonist induced yawning (Urba Holnigren
et al., 1979) and ACTH/MSH peptides may act in
concert with DA receptors to induce yawning
(Bertolini and Gessa, 1981). Sex steroids, in
particular estrogens, also exert a permissive
effect on DA receptor agonist induced yawning
(Argiolas et al., 1998). Since in experimental
animals and humans yawning is induced by L-dopa
as well as by DA receptor agonists (i.e.,
apomorphine) (Mogilnicka and Klimek, 1977; Serra
et al., 1986; Szechtman et al., 1988), one would
expect it to occur frequently in Parkinsonian
patients treated with levodopa or DA receptor
agonists. It remains unclear why in Parkinsonian
patients this phenomenon has not been mentioned
more often in the literature (Goren and
Friedman, 1998). Nevertheless, the occurrence of
yawning and stretching in this patient during
treatment with AC pulsed EMFs may further the
understanding of the mechanisms of action of
magnetic fields on the dopaininergic system in
medicated PD patients.
It has been suggested that yawning is
associated with activation of presynaptic DA
autoreceptors stimulation of which results in
inhibition of DA synthesis and release (Yamada
and Furukawa, 1980; Cooper et al., 1989). In
addition, since anticholinergic drugs block
apomorphine induced yawning, Yamada and Furukawa
(1980) proposed that yawning is mediated by
cholinergie activation secondary to inhibition
of DA transmission. However, some data argue
against this hypothesis (Argiolas and Melis,
199S). Inhibition of DA transmission by other
means such as administration of reserpine or
neuroleptic agents or degeneration of DA neurons
(Mogilnicka and Kliniek, l977 Dourish and
Cooper, 1985) is not associated with yawnirig.
Furthermore, the autoreceptor activation
hypothesis of yawing, has been questioned since
administration of' selective DA-D2 autoreceptor
agonists failed to induce yawing, (Stahle and
Ungerstedt, 1984). Current concepts follow the
investigations of Serra et al. ( 1986, 1987) who
demonstrated that yawning is caused by
activation of postsynaptic DA-D2, receptors
rather than inhibition of DA transmission by
autoreceptor stimulation. In addition. the study
of' Serra et al. (1986) suggested for the first
time, that increased DA release is also required
to elicit a yawning response. If this hypothesis
is correct then yawning induced by transcranial
administration of picotesla flux density E-MFs
is caused by increased presynaptic DA release
associated with stimulation of postsynaptic
DA-D2 receptors.
Levodopa is thought to produce its
antiParkinsonian effect through its
decarboxylation and conversion to DA in
presynaptic neurons thus increasing the synaptic
availability of this transmitter in
doparninergic neurons of the nigrostriatal
pathways. DA-D2 receptors, which are located
postsynaptically on striatal neurons (Reynolds
and Riederer, 1990) are also the principal site
of' action of DA agonist drugs in PD (Kebabian
and Calne. 1979: Schachter et al., 1981,
Gershanik et al., 1983). Yet, the use of
levodopa alone or in combination with DA
receptor agonists has not been associated
yawning and stretching behavior in this or other
PD patients. Moreover. yawning and stretching
have not been observed in unmedicated PD
patients during application of AC pulsed EMFs.
Since in this patient AC pulsed EMF-s were
administered in conjunction with levodopa, it is
concelvable that yawning and stretching
responses resulted from a synergistic
interaction between EMFs and levodopa with EMFs
possibly facilitating the release of DA derived
from levodopa supplementation and simultaneously
causing activation of postsynaptic DA-D2
receptors. Moreover, since stimulation of DA
receptors increases the release of ACTH and MSH
peptides from the pituitary or from peptidergic
neurons in the brain (Bertolini and Gessa, 1981)
and these peptides induced yawning and
stretching behaviors in experimental animals and
humans (Ferrari. l958 Ferrari et al, 1963
Floris, 1963 Gessa et al, l967) it is possible
that a surge in the release of these peptides
reinforced this yawning, and stretching behavior
beyond the duration of EMFs exposure
