Ertekin 2003 Neurophysiology of swallowing

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Invited review
Neurophysiology of swallowing
Cumhur Ertekina,b,*, Ibrahim Aydogdua,b
aDepartment of Clinical Neurophysiology, Ege University, Medical School Hospital, Bornova, Izmir, Turkey
bDepartment of Neurology, Ege University, Medical School Hospital, Bornova, Izmir, Turkey
Accepted 23 June 2003
Abstract
Swallowing is a complex motor event that is difficult to investigate in man by neurophysiological experiments. For this reason, the
characteristics of the brain stem pathways have been studied in experimental animals.
However, the sequential and orderly activation of the swallowing muscles with the monitoring of the laryngeal excursion can be recorded
during deglutition. Although influenced by the sensory and cortical inputs, the sequential muscle activation does not alter from the perioral
muscles caudally to the cricopharyngeal sphincter muscle. This is one evidence for the existence of the central pattern generator for human
swallowing. The brain stem swallowing network includes the nucleus tractus solitarius and nucleus ambiguus with the reticular formation
linking synaptically to cranial motoneuron pools bilaterally.
Under normal function, the brain stem swallowing network receives descending inputs from the cerebral cortex. The cortex may trigger
deglutition and modulate the brain stem sequential activity. The voluntarily initiated pharyngeal swallow involves several cortical and
subcortical pathways. The interactions of regions above the brain stem and the brain stem swallowing network is, at present, not fully
understood, particularly in humans.
Functional neuroimaging methods were recently introduced into the human swallowing research. It has been shown that volitional
swallowing is represented in the multiple cortical regions bilaterally but asymmetrically. Cortical organisation of swallowing can be
continuously changed by the continual modulatory ascending sensory input with descending motor output.
Significance: Dysphagia is a severe symptom complex that can be life threatening in a considerable number of patients. Three-fourths of
oropharyngeal dysphagia is caused by neurological diseases. Thus, the responsibility of the clinical neurologist and neurophysiologist in the
care for the dysphagic patients is twofold. First, we should be more acquainted with the physiology of swallowing and its disorders, in order
to care for the dysphagic patients successfully. Second, we need to evaluate the dysphagic problems objectively using practical
electromyography methods for the patients’ management. Cortical and subcortical functional imaging studies are also important to
accumulate more data in order to get more information and in turn to develop new and effective treatment strategies for dysphagic patients.
q 2003 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
Keywords: Neurophysiology; Swallowing; Deglutition; Central pattern generator; Electromyography; Functional brain mapping
1. Introduction
Swallowing is a complex sensorimotor behaviour invol-
ving the coordinated contraction and inhibition of the
musculature located around the mouth and at the tongue,
larynx, pharynx and esophagus bilaterally. During a
swallow, different levels of the central nervous system
from the cerebral cortex to the medulla oblongata are
involved and many of the striated muscles innervated by
the cranial nerves (CN) are excited and/or inhibited
sequentially for the execution of the passage of bolus from
the mouth to the stomach (Miller, 1982; Jean, 1984, 1986,
2001; Donner et al., 1985; Broussard and Altschuler, 2000a).
Swallowing has received less attention than other
fundamental motor activities such as locomotion, mastica-
tion, or respiration. This is probably due to the complexity
of the motor pattern along with the greater number of
muscles and CN involved, which renders neurophysiologi-
cal studies difficult in experimental animals and humans.
Although recent advances in the evaluation of dysphagia
allow for the diagnosis, prognosis, and treatment of
swallowing problems, such information in human subjects
does not bring much knowledge to the basic understanding
Clinical Neurophysiology 114 (2003) 2226–2244
www.elsevier.com/locate/clinph
1388-2457/$30.00 q 2003 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/S1388-2457(03)00237-2
* Corresponding author. Gönç Apt. Talatpaşa Bulvarı, No: 12 D.3, 35220
Alsancak, Izmir, Turkey. Tel.: þ90-232-4220160; fax: þ90-232-4630074.
E-mail addresses: erteker@unimedya.net.tr (C. Ertekin), iaydog@ttnet.
net.tr (I. Aydogdu).
http://www.elsevier.com/locate/clinph
of the complex physiology of deglutition (Schindler and
Kelly, 2002).
Swallowing and its disorders have been intensively
investigated by videofluoroscopic, manometric and endo-
scopic methods. These studies are especially useful for
clinical problems, however, it is necessary to develop new
techniques, in order to understand the central neural
mechanisms controlling swallowing. This review is limited
to the neurophysiology of oropharyngeal swallowing. The
esophageal phase of swallowing is beyond the scope of this
review.
2. Peripheral events in swallowing
It has become convenient to state that, swallowing is
subdivided into 3 phases: oral, pharyngeal, and esophageal.
This conventional division of the human swallowing is
usually ascribed to Magendie (1825) (Miller, 1982). The
swallow has, however, also been described in two stages i.e.
the buccopharyngeal (or oropharyngeal) and esophageal
stages (Thexton and Crompton, 1998; Jean, 2001).
The 3 phases of swallowing are probably related to their
innervation pattern: the oral phase is often accepted as
voluntary, while the pharyngeal phase is considered a reflex
response, and the esophageal phase is mainly under dual
control of the somatic and autonomic nervous systems
(Doty and Bosma, 1956; Doty et al., 1967; Miller, 1982,
1999). The pharyngeal phase of deglutition involves not
only pharyngeal and laryngeal muscles but also the muscles
in the oral cavity such as tongue and suprahyoid muscles.
The periorbital muscles actively contribute to the involun-
tary swallows. The actual motor events of swallowing can
best be described as being composed of an oropharyngeal
phase (or buccopharyngeal phase) and a subsequent
esophageal phase (Jean et al., 1983; Jean, 1984, 2001;
Ertekin et al., 1998; Ertekin and Palmer, 2000).
The duration of the whole oropharyngeal sequence of
swallowing is short and in the range of 0.6–1.0 s;
remarkably constant in all the mammals studied including
the humans (Ertekin et al., 1995; Ertekin, 1996; Jean, 2001).
In comparison with the extraordinary complexity and
rapidity of the oropharyngeal phase, the esophageal phase
of swallowing is simpler and slower. It consists of a
peristaltic wave of contraction of the striated and smooth
muscles, which propagates to the stomach. The whole
esophageal phase may exceed 10 s in the conscious human
(Jean, 1972, 2001; Miller, 1999). For the sake of better
understanding, oropharyngeal swallowing can be reviewed
separately under the two titles, oral and pharyngeal phases.
2.1. Oral phase of swallowing
The oral phase of swallowing is mainly voluntary and
highly variable in duration depending upon taste, environ-
ment, hunger, motivation, and consciousness for the human
subject. Its primary function is the movement of the tongue,
pressing the bolus against the hard palate, and initiating the
movement of bolus to the posterior part of the tongue and
toward the oropharynx. The suprahyoid muscles of the floor
of the mouth are particularly important to elevate the
tongue, especially for solid bolus. In this stage, the
contraction of the lips and cheek muscles (i.e. orbicularis
oris and buccinator muscles) are crucial to prevent the
escape of solid or liquid fromthe oral cavity (VII CN). This
stage is ended by the triggering of the pharyngeal phase of
swallowing. The nature of the triggering of the pharyngeal
phase of swallowing is not clearly known.
It is generally assumed that the afferent fibers involved in
the initiation of swallowing are those running within the
maxillary branch of the trigeminal nerve, the glossophar-
yngeal nerve, and the vagus nerve, especially its superior
laryngeal branch (Miller, 1972, 1982, 1986, 1999). These
nerves innervate peripheral areas such as the dorsum of the
tongue, the epiglottis, the pillar of the fauces and the walls of
the pharynx. Tactile, chemical, and electrical stimulations
can induce swallowing in experimental animals (Miller,
1972, 1982, 1986, 1999; Kessler and Jean, 1985). At the
brain stem level, all the afferent fibers involved in initiating
or facilitating swallowing converge in the solitary tract and
end in the nucleus tractus solitarius (NTS). Therefore, the
NTS constitutes the main afferent central structure (Kalia
and Mesulam, 1980; Contreras et al., 1982; Miller, 1999;
Jean, 2001). The NTS not only receives the main sensory
fibers from the oropharyngeal and laryngeal regions, but also
cortical descending inputs reach similar areas of the NTS.
Some sensory inputs that initiate swallowing are transmitted
to the region of the cortex that facilitates the initiation of the
swallowing. It is possible that during repeated swallowing,
descending signals from the cortical sites associated with
swallowing decrease the threshold to evoke swallowing
(Miller et al., 1997; Thexton and Crompton, 1998; Miller,
1999). These data are obtained from experimental research
studies in animals. However, the initiation or triggering of
swallowing is probably more complex in humans and may
depend more on regions above the brain stem. It may be
dependent on the type of bolus, single or continuous
swallows and voluntarily or reflexively induced swallowing.
Some factors seem to modulate the initiation of the
voluntarily induced swallows in man. These are the bolus in
the mouth (food or saliva), corticobulbar drive to the tongue
muscles (XII CN), and the submental/suprahyoid muscles at
the floor of the mouth (V and XII CN). The triggering of the
spontaneous swallows probably does not require cortical
drive but could involve communication with the cortex and
subcortical regions, and can occur between meals and
during non-REM sleep; and depends on the amount of saliva
accumulated in the mouth (Lear et al., 1965; Lichter and
Muir, 1975; Sochaniwskyj et al., 1986; Pehlivan et al., 1996;
Ertekin et al., 2001a).
There is no doubt that the mechanoreceptors, chemo-
receptors, and thermoreceptors in the oral cavity, tongue,
C. Ertekin, I. Aydogdu / Clinical Neurophysiology 114 (2003) 2226–2244 2227
and pharynx provide information essential to bolus
identification. Sensory inputs from the oropharyngeal
region, especially the tonsillar pillars, base of the tongue,
and oropharyngeal mucosa have been proposed to be
important for the triggering of swallows (IX and X CN)
(Miller, 1972, 1999; Mansson and Sandberg, 1974, 1975a;
Hollshwander et al., 1975; Hacker and Cattau, 1978;
Nishino, 1993; Ali et al., 1994; Ertekin et al., 2000a, 2001a).
In most human studies, such as studies of continuous
drinking or eating, it has been reported that a swallow is not
induced by water infusion into the valleculae until the liquid
reached the pyriform sinuses and aryepiglottic folds
(Pouderoux et al., 1996; Thexton and Crompton, 1998). A
swallow, however, may be initiated earlier when the bolus
makes contact with the upper third of the epiglottis than
when it is confined to the valleculae and pyriform sinuses at
the pharynx (Dua et al., 1997; Thexton and Crompton,
1998).
In normal human subjects, it is evident that there is
usually a gradual accumulation of prepared food on the
posterior surface of tongue, and this solid food reaches the
valleculae in advance of the initiation of the swallow
(Palmer et al., 1992; Thexton and Crompton, 1998). The
mucosa of the hypopharynx and around the larynx needs to
be intact where the sensory signals may elicit the pharyngeal
reflex swallows in man (Palmer et al., 1992; Pouderoux
et al., 1996; Ertekin et al., 2000a). Thus, the initiation of the
swallow can be expected from the posterior part of the oral
cavity to the hypopharynx depending on the different kinds
of bolus.
In a small volume swallow (1–2 ml) such as saliva, there
is no oral preparation, and the oral and pharyngeal stages
occur in sequence. In contrast, when taking a large volume
liquid bolus, the oral and pharyngeal stages overlap with
each other, occurring simultaneously (Logemann, 1998;
Ertekin and Palmer, 2000). The size of the bolus does not
alter the sequence of events during oropharyngeal swallow-
ing but modulates the timing of each part of the swallow
(Ertekin et al., 1997). As the bolus size increases (1–20 ml),
the pharyngeal transit time increases, as do laryngeal
closure and elevation (Ertekin et al., 1997; Logemann,
1998). After 20 ml volume of water, normal subjects tend to
divide the liquid into two or more segments (Ertekin et al.,
1996). This is called piecemeal deglutition. Patients with
neurogenic dysphagia are obliged to divide the bolus into
two or more swallows successively, below the 20 ml volume
of drinking water (Ertekin et al., 1996, 1998) (Fig. 1).
Although the site, timing and density of the orophar-
yngeal sensory input may vary from one bolus to another,
and from normal subjects to the patients with sensory
impairment, once swallowing is initiated, the cascade of the
sequential muscle activation does not essentially alter from
the perioral muscles downward. This is one of the lines of
evidence for the existence of the central pattern generator
(CPG) for the human swallowing that will be discussed
later.
2.2. Pharyngeal phase of swallowing
As it was mentioned above, the oral cavity and pharynx
are anatomically separated but functionally integrated
regions of the head and neck. These two regions are
involved in the complex motor responses that include
feeding, chewing, swallowing, speech, and respiration.
From the point of swallowing, the oral and pharyngeal
phases are highly interrelated and the distinction between
them is often unclear. Therefore, we often use the term
oropharynx and oropharyngeal swallowing due to their
intimate interrelationship. When the movement of the bolus
from the oral cavity to the pharyngeal spaces triggers the
swallowing reflex or response, the following physiological
events occur in rapid overlapping sequence. All of the
events until the esophageal phase are mainly controlled by
the CPG of the brain stem (Miller, 1982, 1999; Jean, 2001).
These events are as follows:
1. The nasal, laryngeal and tracheal airway is protected by
several “reflex” events including closure of the velo-
pharyngeal isthmus by the palate, laryngeal elevation and
suspension by suprahyoid/submental muscles and clo-
sure of the larynx by laryngeal muscles of the vocal folds
and epiglottis. Laryngeal elevation is a vital component
of the airway protection as this action does not only
facilitate closure of the vestibulae but also repositioning
of the larynx anterosuperiorly under the tongue base. All
swallows take place somewhere between late inspiration
and late expiration, and there is always an apneic period
during the pharyngeal phase of swallowing (Nishino
et al., 1985; Martin et al., 1994; Paydarfay et al., 1995;
Thexton and Crompton, 1998). Protection of the airway
is essential owing to the CPG. The orolaryngopharyngeal
protective reflexes also support the laryngeal closure
according to the urgent need.
2. The tongue thrusts posteriorly to push the bolus
throughout the pharynx and into the esophagus (XII
CN). A sequential wave of contraction of the pharyngeal
constrictor muscles (XCN) clears any remaining
material into the esophagus. The main propulsive force
acting on the bolus is thus, provided by the posterior
movement of the tongue (Kahrilas et al., 1992; Thexton
and Crompton, 1998). The pharyngeal contraction seems
to be minimal in relation to bolus propulsion, although it
facilitates subsequent pharyngeal clearance in associ-
ation with a profound shortening of the pharynx
(Kahrilas et al., 1992).
3. The upper esophageal sphincter (UES) relaxes and
opens for the bolus transport into the esophagus. The
UES consists primarily of the tonically contracting
striated cricopharyngeus muscle. During a swallow,
this muscle relaxes and is opened and the sphincter is
pulled upon anteriorly by the contraction of the supra-
hyoid/submental muscle groups. Then the pharyngeal
C. Ertekin, I. Aydogdu / Clinical Neurophysiology 114 (2003) 2226–22442228
Fig. 1. The integrated orbicularis oris (O. Oris) (top traces in each pair) and submental muscle electromyography (SM-EMG) (lower trace in each pair)
activities (surface electrodes) during swallowing of different amounts of water, increasing in quantity step by step from 3 to 20 ml. Note that all volumes were
swallowed at one go up to 20 ml in a normal adult subject (A), while, in a stroke patient with dysphagia (B), the bolus is divided into two or more separate
swallows during the swallowing of 10–20 ml water. (Arrows indicate the second and subsequent swallows). The sweep duration set at 10 s and the delay line
was adjusted to O. Oris at 2 s. Amplitude calibration: 70 mV (A) and 50 mV (B). Time calibration: 1000 ms in all traces.
C. Ertekin, I. Aydogdu / Clinical Neurophysiology 114 (2003) 2226–2244 2229
phase of swallowing is completed and the UES closes
until the next swallow.
During a swallow, the UES opens and the tonic EMG
activity of the CP sphincter muscle ceases simultaneously
(Ertekin et al., 1995; Ertekin and Aydogdu, 2002). For the
physiology of the relaxation of the CP muscle and the
opening of the UES, there are two diverse opinions.
According to one view, the cessation of tonic activity of
the CP muscle is believed to be due to a neural inhibition,
possibly originating from the CPG at the medullary level
(Doty and Bosma, 1956; Jean and Car, 1979; Miller, 1982;
Ertekin et al., 1998, 2000c; Ertekin and Aydogdu, 2002).
The contrary view is that the opening of the UES, together
with the cessation of the tonic activity are brought about by
traction of the suprahyoid muscles, which produce the
anterior displacement of the larynx (Asoh and Goyal, 1978;
Goyal, 1984; Ekberg, 1986; Dodds et al., 1988; Cook et al.,
1989; Jacob et al., 1989; Lang et al., 1991).
Probably, the mechanism of the opening and relaxation
of the CP muscle of the UES is under neural control rather
than biomechanical causes, since the relationship and
correlation between the laryngeal relocation time and the
opening of the UES found in normal subjects (Kahrilas et al.,
1988; Cook et al., 1989; Jacob et al., 1989; Ertekin et al.,
1997), clearly disappear in dysphagic patients with
suprabulbar palsy due to different nervous system disorders
(Ertekin et al., 2000b,c).
3. EMG in swallowing muscles
The sequential and orderly activity of swallowing
muscles can be demonstrated by EMG methods. Consider-
able number of studies have been performed for swallowing
muscles in experimental animals and to some extent in man.
Doty and Bosma (1956) described the pattern of EMG
activity in the oral and pharyngeal muscles in dog during
swallowing elicited reflexively by electrical and mechanical
stimuli. The pattern of EMG activity reported in that study
and others subsequently, suggests the concept of a temporal
pattern of sequential activation where the latency of a burst
of EMG activity broadly reflects the distance of that muscle
from the entrance of the mouth to the esophagus. EMG
activity in each individual muscle consists of a phasic
discharge in the form of a burst of EMG spikes which ranges
in general between 200 and 800 ms depending on the muscle
and the species including humans (Doty and Bosma, 1956;
Hrycyshyn and Basmajian, 1972; Ertekin et al., 1995;
Perlman et al., 1999; Jean, 2001).
In addition to the bursts, when background activity is
present in the muscles, there is a shorter inhibition, which is
maintained until the actual swallowing contraction begins as
a burst. A strong inhibition of the background activity is also
observed after the phasic discharge. Therefore, the orophar-
yngeal stage comprises an extraordinary sequence of
inhibition and activation in pairs of swallowing muscles
which have to be synchronised during the motor sequence.
Once this complex motor sequence has been initiated, it
invariably reaches the UES. Although some sensory inputs
from the oropharynx may modulate the contractions, the
basic program is not prevented (Jean, 2001). This is one of
the characteristics of the CPG of swallowing.
In an attempt to study the swallowing muscles by EMG, a
few approaches can be used:
Almost all of the muscle pairs related to deglutition can be
recorded experimentally from the mouth level to the end of
the pharynx. It is not practical to evaluate electromyogra-
phically all pairs of oropharyngeal swallowing muscles in
human studies. This is because it is difficult to reach some
muscles superficially. However, a computer-aided method
for calculating the independent components of several
simultaneous surface EMG recordings from the face to the
lower neck has recently been reported and demonstrated that
it can be possible to approach the sequential muscle
activation during swallowing in man (McKeown et al.,
2002). We will have to wait for confirmatory studies on this
line.
Instead of recording from many muscles, it is usually more
logical to record the EMG activity in a few but important
deglutition muscle groups using superficial electrodes. One
needle electrode or a wire electrode can be used for the
deep-seated swallowing muscles (Perlman et al., 1999).
The oropharyngeal and esophageal systems possess
certain reflexes that may modify the swallowing and
they may be protective against the unpredictable passage
of bolus during a swallow. These kinds of protective
reflexes can also be studied by providing natural or
electrical stimuli to the oropharynx with some target
deglutition muscles recorded either superficially or by
needle electrodes (Hiiemae and Crompton, 1985; Miller,
1999).
There are several groups of muscles of deglutition that
were studied in detail:
1. Jaw and perioral muscles
2. Submandibular/suprahyoid muscles
3. Tongue muscles
4. Laryngeal and pharyngeal muscles
5. CP muscle of the UES.
The first two groups of muscles are the easiest to pick up
EMG activity superficially while the latter 3 groups are
approached by needle electrodes or by means of intralumi-
nar catheter electrodes.
3.1. Jaw and perioral muscles
The oral phase of swallowing consists of both voluntary
control and reflexive components integrated with feeding
C. Ertekin, I. Aydogdu / Clinical Neurophysiology 114 (2003) 2226–22442230
and chewing (Hiiemae and Crompton, 1985; Miller, 1999).
The oral phase of swallowing recruits the jaw closing
muscles of the mandible (i.e. temporalis, masseter and
medial pterygoid) to stabilise the mandible. As a result, the
type of bolus affects the recruitment of the jaw closing
muscles, and more EMG activity occurs when greater
stabilisation of the mandible is needed (McNamara and
Moyers, 1973; Miller, 1982, 1999; Thexton, 1992). During
pharyngeal swallowing, the jaw closing muscles may
stabilise the mandible.
The masseter muscle can be superficially recorded
together with the submental muscle group and their
relationship is in sequence. It is the first in EMG activation
and the submental muscles are subsequently activated while
the larynx is being raised by the hyoid bone with the
contraction ofthe submental/suprahyoid muscles. The end
result is the protection of the upper airway during transfer of
the bolus.
Similarly, the perioral-facial muscles are the first recruits
during the oral phase of swallowing to provide an anterior
seal of the lips (Logemann, 1998; Murray et al., 1998;
Miller, 1999). In normal human subjects, orbicularis oris
and buccinator muscles firmly close the mouth to prevent
food from escaping, flatten the cheeks and hold the food in
contact with the teeth (Perlman and Christenson, 1997; Secil
et al., 2002). Their contraction and muscle tone act as a
valve mechanism (Logemann, 1996, 1998). It has been
observed that the perioral muscle activity is ended just
before the pharyngeal phase of swallowing, while the
masseter activity can continue or reappear during the
pharyngeal phase of swallowing (Ozdemirkıran, 2002)
(Fig. 2).
3.2. Submandibular/suprahyoid muscles (SM muscles)
The SM muscle complex (mylohyoid, geniohyoid and
anterior digastric muscles) fires concurrently to initiate a
swallow and function as the laryngeal elevators pulling the
larynx upward (Miller, 1982; Donner et al., 1985; Jacob
et al., 1989; Gay et al., 1994; Martin et al., 1994; Schultz
et al., 1994; Ertekin et al., 1995; Perlman and Christenson,
1997; Logemann, 1998). For this reason, surface EMG
activity of the SM muscles gives a considerable amount of
information about the onset and duration of the orophar-
yngeal swallowing, because the contraction of the SM
muscles pulls up the hyoid bone into an anterosuperior
position, which elevates the larynx and initiates other
reflexive changes that constitute the pharyngeal phase of
swallowing (Donner et al., 1985; Jacob et al., 1989; Dodds
et al., 1990; Ertekin et al., 1995, 2000a, 2001a). Movements
that occur from the beginning of SM muscle contraction to
the elevation of the larynx are important for the safe passage
of bolus to the pharyngoesophageal segment without
escaping into other cavities. The contraction of SM muscles
continues until the completion of the oropharyngeal
swallowing process (Donner et al., 1985; Gay et al., 1994;
Ertekin et al., 1995, 1998; Ertekin, 1996).
When a swallow is initiated voluntarily, the contraction
of the SM muscles should be controlled by at least two
routes. During the initial part, SM muscles should be
activated by the cortical drive either directly or via the brain
stem CPG. The latter part of SM muscle activation should,
however, be controlled by the CPG of the brain stem
network, especially in the period immediately after the onset
of laryngeal upward movement, which is an important and
Fig. 2. The sequential muscle activation during 3 ml water swallowing in a
normal subject. Uppermost trace is the laryngeal movement sensor
(laryngeal sensor). Onset of upward movement of the larynx is
demonstrated by the arrow (the onset of pharyngeal phase) and the
beginning of the downward movement of the larynx was recorded as a
positive deflection. The time interval between the onsets of two deflections
indicates the upward movement of the larynx plus the relocation time
during the pharyngeal phase of swallowing. The orderly activation of the
orbicularis oris, masseter, submental, thyroarytenoid and cricopharyngeal
(CP) muscles is obtained from 5 superimposed EMG traces (needle
recording in all but surface recording from the masseter and submental
muscles). The arrows are the onset of EMG burst of each muscle except the
CP sphincter muscle in which the onset of EMG pause (opening of the CP
sphincter) is shown. Note the sequential and orderly activation of the
muscles and EMG pause in CP sphincter during oropharyngeal swallowing.
Amplitude calibration: 50, 30, 70, 100 and 50 mV for EMG traces
(amplitude of laryngeal sensor signal is unimportant). Time calibration: 200
ms in all traces. The amplitudes of EMG in submental muscles and CP
sphincter muscle were cut off by too high a gain on the amplifier.
C. Ertekin, I. Aydogdu / Clinical Neurophysiology 114 (2003) 2226–2244 2231
early event of the pharyngeal phase in voluntarily induced
deglutition (Dodds et al., 1990; Perlman et al., 1995; Ertekin
et al., 2001a). In many of the dysphagic patients, the onset of
SM-EMG is extremely prolonged, which indicates the
difficulties of the cortically induced triggering mechanism
due to the involvement of the corticobulbar fibers (Ertekin
et al., 1998, 2000b,c, 2001b).
3.3. Tongue muscles
Intrinsic fibers of the tongue muscle are very difficult to
investigate by surface EMG electrodes except in transcra-
nial magnetic stimulation (TMS) studies (Muellbacher et al.,
1994; Urban et al., 1996; Meyer et al., 1997). Surface
electrodes are prone to recording artefacts, and it is difficult
to fix them in the oral cavity during swallowing. Some EMG
studies have been performed by using wire electrodes
(Cunningham and Basmajian, 1969; Vitti et al., 1975;
Cooper and Perlman, 1997). The genioglossus muscle has
been mostly investigated by this method. Ultrasonographic,
CAT scan, and some MRI studies seem to be superior for the
deglutition studies of the tongue (Brown and Sonies, 1997).
3.4. Laryngeal and pharyngeal muscles
EMG recordings of the pharyngeal and laryngeal
muscles are not frequently investigated during deglutition.
The reason is related to the difficulty in approaching these
muscles non-invasively. Therefore, it is generally preferred
to insert a needle electrode with the help of a laryngologist.
Some laryngeal and pharyngeal muscles can be reached by
percutaneous needle insertion or wire electrodes (Perlman
et al., 1989, 1999; Schaefer, 1991; Spiro et al., 1994;
McCulloch et al., 1996; Ertekin et al., 2000c,d). Examples
involve the insertion to the thyroarytenoid muscle and the
vocalis muscles as the laryngeal adductors (Hiroto et al.,
1968; Mu and Yang, 1990; Schaefer, 1991; Yin et al., 1997)
and the cricothyroid muscle (Schaefer, 1991; Yin et al.,
1997).
When the larynx is pulled up anterosuperiorly by the SM
muscles during the pharyngeal phase of swallowing, the
laryngeal adductor muscles are activated for the closure of
the vocal cords. By this mechanism, the larynx and lower
airways are thought to be protected from swallowing bolus
that is passing through the pharynx. Laryngeal adductor
muscles including the thyroarytenoid muscle are mainly
activated for the protection of the larynx during swallowing.
The protective activity of the laryngeal adductors usually
begins after the contraction of the SM muscles in both
voluntarily initiated and spontaneous reflex swallows. Thus,
the activities of both groups of muscles are interrelated
through the CPG of the swallowing program (Ertekin et al.,
2000d). There are two additional EMG activities that are
sometimes recorded and may have different roles; one
adductor activity is observed just before swallowing and
occurs very close but prior to the upward movement of
the larynx (Fig. 3). This foreburst EMG activity appears to
be related to the polysynaptic laryngeal reflex mechanisms
that are triggered by the intraoral inputs and it is protective.
Another EMG activity of the laryngeal adductors is
recorded during the downward movement of the larynx,
just after the end of the swallowing. This activity might be
related to a fast and strong expiratory movement at the
laryngeal folds (Ertekin et al., 2000d). In fact, the laryngeal
Fig. 3. Thyroarytenoid EMG (rectified and integrated) activity of a normal subject with simultaneous recording of laryngeal vertical movement during
swallowing of 3 ml water. The onset of upward deflection of the larynx is denoted by “0” and that of downward by “2”. Five traces were averaged in all.
“Onset” and “End” belong to basic activity (from Ertekin et al., 2000d; by permission).
C. Ertekin, I. Aydogdu / Clinical Neurophysiology 114 (2003) 2226–22442232
adductor reflex has been documented in response to the
electrical stimulation ofthe superior laryngeal nerve (SLN)
indicating that this is a polysynaptic brain stem reflex
(Sasaki and Suzuki, 1967; Sasaki and Buckwalter, 1984).
During deglutition, normal subjects always inhibit
respiration, which is sometimes called the swallowing
apnea and normal swallowing usually interrupts the
expiratory phase of the respiratory cycle (Miller, 1982;
Dodds, 1989; Dodds et al., 1990; Martin et al., 1994). After
the swallow, normal subjects always resume breathing with
expiration (Preiksaitis et al., 1992; Paydarfay et al., 1995).
As a pharyngeal muscle, the superior pharyngeal
constrictor muscles are investigated using bipolar hooked
wire electrodes (Hairston and Sauerland, 1981; Perlman
et al., 1989). Swallowing produces significantly dense EMG
activity which lasts about 800 ms that is almost equal to that
of the SM-EMG (Perlman et al., 1989).
3.5. Cricopharyngeal muscle of the upper esophageal
sphincter
CP muscle is a striated muscle sphincter situated at the
pharyngoesophageal junction. It is one of the most
important muscles for the evaluation of neurogenic
dysphagia (Ertekin et al., 1995, 1998). EMG of the CP
sphincter muscle has been studied in a variety of subhuman
species to understand deglutition (Doty and Bosma, 1956;
Kawasaki Ogura and Takenovchi, 1964; Levitt et al., 1965;
Murakami et al., 1972; Asoh and Goyal, 1978; Venker-van
Haagen et al., 1989; Lang et al., 1991; Medda et al., 1997),
however, it has seldom been reported in healthy human
subjects and patients (Shipp et al., 1970; Hellemans et al.,
1974; Van Overbeek et al., 1985; Tanaka et al., 1986; Elidan
et al., 1990a,b; Ertekin et al., 1995; Ertekin and Aydogdu,
2002).
There are two main approaches to recording from the CP
muscle: the percutaneous and intraluminal approaches. In
the percutaneous approach, a concentric needle electrode is
passed through the skin in a posterior and medial direction
at the level of and just lateral to the cricoid cartilage (Ertekin
et al., 1995, 1998; Ertekin and Aydogdu, 2002). A hook-
wire electrode can also be used for this approach (Perlman
et al., 1989, 1999; Perlman, 1993). The intraluminal
approach to the CP muscle has mostly been used in the
past. The wire electrodes are introduced by an endoscopic
procedure under general anesthesia (Van Overbeek et al.,
1985) or during oropharyngeal operations (Mu and Sanders,
1998; Sasaki et al., 1999; Brook et al., 1999). CP muscles
have also been investigated by bipolar suction electrodes
together with pharyngeal topical anesthesia (Palmer, 1989;
Palmer et al., 1989).
The CP sphincter muscle is tonically active during rest
and this continuous activity ceases during a swallow in
human subjects. During wet or dry swallowing, two
bursts of increased EMG activity are clearly observed
just before and after the CP-EMG pause. The foreburst
may be a kind of protective reflex strictly related to
oropharyngeal function and does not necessarily take part
in the sequential muscle activity of deglutition, whereas
the rebound activity is an electrical event that is strictly
bounded by the CPG (Ertekin and Aydogdu, 2002).
Foreburst of the CP muscle is similar to that obtained
from the laryngeal adductor muscle (Ertekin et al.,
2000d) (see Fig. 2, bottom trace).
During a swallow, tonic motoneurons supplying the CP
muscle are first inhibited and the CP sphincter is relaxed.
Consequently, during the rebound burst, phasic larger
motoneurons fire transiently to close the sphincter as fast
as possible after passage of the bolus and the tonic
motoneurons are re-excited. Although both units are under
the control of the CPG, both are also influenced by sensory
and cortical inputs (Ertekin et al., 2000a,b; Ertekin and
Aydogdu, 2002).
4. Brain stem and swallowing
We owe almost all our knowledge to experimental
deglutition studies except some information that was
generated by clinical studies. Therefore, most of the
information related to the brain stem and swallowing has
been obtained from non-human mammals.
The precise pattern of muscle contraction and inhibition
sequentially as mentioned above is dependent on brain stem
neural structures that conceptually consist of 3 levels
(Broussard and Altschuler, 2000b):
1. An afferent and/or descending input level that corre-
sponds to sites of termination of peripheral and central
swallowing afferent fibers.
2. An efferent level that corresponds to the motoneuron
pools of the cranial motor nuclei that provide innervation
to swallowing muscles.
3. An organising level that consists of an interneuronal
network of “premotor” neurons in contact with both
afferent and efferent levels.
These premotor neurons or interneurons, which can
initiate or organise the swallowing motor sequence, are
known as the swallowing CPG (Jean, 1972, 1978, 2001;
Jean et al., 1975; Miller, 1982; Bieger, 1984; Kessler and
Jean, 1985). The experimental electrophysiological studies
and the introduction of axoplasmic tracing techniques have
demonstrated that swallowing premotor neurons are located
within the NTS, the adjacent reticular formation surround-
ing NTS and in the reticular formation around and just
above the nucleus ambiguus (NA) of the ventrolateral
medulla oblongata (Jean, 1984, 2001; Kessler and Jean,
1985; Broussard and Altschuler, 2000b).
Thus, the swallowing interneurons or premotor neurons
are located in these two main brain stem areas: the dorsal
swallowing group (DSG) in and around NTS and ventral
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swallowing group (VSG) just above the NA (Jean, 1972,
2001; Jean and Car, 1979; Amri et al., 1984; Kessler and
Jean, 1985; Ezure et al., 1993; Umezaki et al., 1998).
Swallowing premotor neurons might be involved in the
bilateral and rostrocaudal coordination of the multiple
motoneuronal pools. Experimental data suggest that within
the swallowing network in the medullary level, VSG
neurons are activated via DSG neurons and that all
motoneurons of swallowing in the V, VII, IX, X, and XII
motoneuron pools are driven by the premotor neurons of the
VSG (Holstege et al., 1977; Jean et al., 1983; Jean, 2001).
As shown in Fig. 4, the swallowing CPG includes two
main groups of premotor neurons and motoneurons located
within the NTS and the adjacent reticular formation and
VSG located in the ventrolateral medulla adjacent to the
NA. The DSG contains the generator neurons involved in
the triggering, shaping and timing of the sequential or
rhythmic swallowing pattern. The VSG contains the
switching neurons, which distribute the swallowing drive
to the various pools of the motoneurons involved in
swallowing (Jean, 2001). These premotor neurons excite
the motoneuron pools bilaterally from VSG. During the
functioning of the swallowing network, both excitatory and
inhibitory drives can be exerted along the anatomical
pathways (Zoungrana et al., 1997).
In fact the CPG for swallowing consists of two hemi-
CPGs each located on one side of the medulla. Under
physiological conditions, the two hemi-CPGs are tightly
synchronised and organise the contraction of the bilateral
muscles of the oropharyngeal region (Doty et al., 1967;
Jean, 2001). Anatomical connections mediated by nerve
fibers crossing the midline have been found to exist
between the two medullary regions, where swallowing
neurons are located in the DSG and VSG (Jean et al.,
1983). Thus, the swallowing motor sequence is mainly
generated in the ipsilateral hemi-CPG and this CPG
transfers the swallowing pre-motoneuron signals to the
contralateral CPG (Jean, 2001). Swallowing NTS neurons
play a crucial role in these synchronisation processes.
The dual swallowing centers on both sides of the
medullary region and their extensive connections are
important in understanding the nature of dysphagia in
Wallenberg syndrome in man. Lateral medullary infarc-
tion should primarily affect the NTS andin particular the
NA and their vicinity in the medulla oblongata
unilaterally. With the use of MRI, it has been demon-
strated that in a lateral medullary infarction resulting in
dysphagia and aspiration, the rostral and dorsolateral
parts of the medulla are affected (Kim et al., 1994, 2000;
Vigderman et al., 1998).
A transverse section through the medulla corresponding
approximately to the rostral third to fourth of the principal
(inferior) olivary nucleus contains the site at which the NTS
and NA are almost equally affected by the occlusion of the
posterior inferior cerebellar artery (Haines, 1991). Although
a lesion of the lateral medullary infarction in human is
unilateral, its effect on oropharyngeal swallowing is
bilateral (Aydogdu et al., 2001), probably because the
premotor neurons in and around NA and their connections
are affected. Consequently, a disruption and/or disconnec-
tion of their linkage to swallowing-related cranial motor
neuron pools bilaterally and to the contralateral NA could
produce the swallowing disorders in Wallenberg syndrome.
The remaining intact ipsilateral premotor neurons and the
contralateral center in the medulla oblongata may even-
tually begin to operate and overcome the severity and long-
term persistence of dysphagia (Aydogdu et al., 2001)
(Fig. 5).
It is generally assumed that the afferent fibers involved in
the initiation of swallowing are those running within the
maxillary branch of the trigeminal nerve, the glossophar-
yngeus and vagus nerve especially its SLN (Miller, 1972,
Fig. 4. Schematic representation of the central pattern generator of swallowing. Peripheral and supramedullary inputs reach to and around nucleus tractus
solitarius–dorsal swallowing group (NTS-DSG). NTS-DSG activates the ventral swallowing group of premotor neurons in the ventrolateral medulla–ventral
swallowing group (VLM-VSG) adjacent to the nucleus ambiguus (NA). VLM-VSG drives the motoneuron pools of the V, VII, IX, X, XII, C1–3 CN bilaterally
(modified from Jean, 2001).
C. Ertekin, I. Aydogdu / Clinical Neurophysiology 114 (2003) 2226–22442234
1986). Sensory inputs can be initiated and continued either
by mucosal receptors of the oropharynx and/or by lingual
and/or palatopharyngeal mechanoreceptors during the
swallowing of the saliva, liquid or solid foods (Miller,
1972; Mansson and Sandberg, 1974, 1975a,b; Ertekin et al.,
2000a). It has been demonstrated that the variables of
oropharyngeal swallowing can be modified by changes in
bolus volumes (Kahrilas et al., 1988; Cook et al., 1989;
Jacob et al., 1989; Dantas et al., 1990; Ertekin et al., 1997).
It is believed that sensory feedback originating from the
oropharyngeal mucosae and deeper receptors in the region
may modify the CPG of the bulbar swallowing network
(Miller, 1982). However, there has been much debate about
the effects of mucosal receptors on oropharyngeal degluti-
tion, because of the discrepancy among the studies of topical
anesthesia of the oropharynx (Mansson and Sandberg, 1974;
Hollshwander et al., 1975; Hacker and Cattau, 1978;
Nishino, 1993; Ali et al., 1994). On the other hand, the
sensory deficit in the oropharyngeal mucosae has been
proven to be one of the important causes of dysphagia and
aspiration in stroke patients (Aviv et al., 1996, 1997).
Results obtained during topical anesthesia of the orophar-
yngeal mucosae in human subjects suggest that adequate
sensory inputs are necessary for the perception of the bolus
volume and viscosity by the cerebral cortex and the bulbar
swallowing network (Ertekin et al., 2000a). The insuffi-
ciency of the sensory coding would produce an “uncertain
evaluation” in the central nervous system. The main role of
the oropharyngeal mucosal receptors may be to contribute to
the initiation of swallowing, but when swallowing is
triggered, the pattern and sequential activity of swallowing
is not essentially changed (Ertekin et al., 2000a; Aydogdu
et al., 2001). The sensory inputs physiologically modulate
the central network activity to adapt the forthcoming motor
sequence to the information arising from peripheral
receptors. The continuous sensory feedback may influence
the CPG and thus modulate the central programs (Jean,
1984).
At the central level, all the afferent fibers involved in the
initiation or facilitation of swallowing converge and
terminate in the NTS. Thus, the NTS constitute the main
afferent central structure involved in swallowing (Jean,
2001). In addition to the peripheral and suprasegmental
descending inputs, there may exist a rostrocaudal inhibition
within the swallowing network (Jean, 1972, 1984; Otake
et al., 1992). The swallowing neurons controlling the distal
parts of the swallowing tract are inhibited when neurons
controlling the more proximal regions are excited (Jean,
1972). In this way, inhibition– excitation and again
inhibition are successively transmitted throughout the
swallowing network (Jean, 2001). The excitatory and
inhibitory messages are transferred from NTS to the
motoneuronal levels (Zoungrana et al., 1997). The result
is a successful sequential activation and inhibition of the
swallowing muscles.
Within the swallowing CPG, some premotor neurons and
motoneurons can be involved in at least two different tasks,
such as swallowing and respiration, swallowing and
mastication or swallowing and phonation (Jean, 2001).
Therefore, common motoneurons may be involved in these
activities. Some recent results have indicated that inter-
neurons in DSG or VSG regions of the swallowing network
also fire several motor behaviours such as swallowing,
respiration, mastication and vocalisation (Kessler, 1993;
Chiao et al., 1994; Oku et al., 1994; Jean, 2001). The
common motoneurons might, therefore, be triggered by
common pools of interneurons. It can be proposed that in
mammals, the neurons liable to be involved in pattern
generation can belong to different CPGs. Multifunctional
neurons of this kind would make for great functional
flexibility for mammals. It also appears that within the
dorsal and ventral medulla there exists a common pool of
neurons that might have multifunctional roles. Some of the
components of the swallowing network are not dedicated to
swallowing alone but can also serve some purpose in other
central networks (Jean, 2001).
Fig. 5. Swallowing associated connectivity of medulla oblongata and the
regions affected by lateral medullary infaction (LMI). Top, area affected by
LMI (shaded area) and the involvement of nucleus tractus solitarius and
nucleus ambiguus in this region. Bottom, schematic representation of
premotor neurons and their ipsilateral connections to V, VII, IX, X and XII
cranial motor neuron pools and the contralateral swallowing center (from
Aydogdu et al., 2001; by permission).
C. Ertekin, I. Aydogdu / Clinical Neurophysiology 114 (2003) 2226–2244 2235
Little is known so far about synaptic transmitter
mechanisms in brain stem swallowing CPG, even in
experimental fields. Among the various neurotransmitters
that are known to intervene in deglutition, the excitatory
amino acid (EAA) receptors, in particular those of the
NMDA type, play an important role in triggering the motor
event and patterning the motor sequence. Especially the fast
information transfer uses EAA transmission by means of
several glutamate receptors subtypes (Jean, 2001; Bieger,
2001).
Inhibitory phenomena were reported to be associated by
the GABAergic mechanism (Jean, 2001; Bieger, 2001).
Local and reticular cholinergic neurons are implicated in
pharyngoesophageal coupling in deglutition and the gener-
ation of propulsive esophagomotor output (Bieger, 1991,
2001).
As we have stated at the beginning of the review, the
pharyngeal phase of the swallowing is controlled by the
medullary CPG. The effects of the cortical control on
the bulbar CPG are rather complex on the oropharyngeal
swallowing as a whole in human subjects.For example, it
can be said that material in the mouth (food or saliva) and
the cortical drive to the tongue and the floor of the mouth are
necessary for the initiation of the voluntarily induced
swallows, whereas the triggering of the spontaneous
swallows do not require any cortical drive. However, a
reflex mechanism should play a role in both swallowing
types. Perioral, submental, and lingual striated muscles can
be controlled by the medullary CPG beyond the cortical
drive. This can be shown by the EMG recording from those
muscles mentioned above, during a spontaneous swallow-
ing. In addition to the control of medullary CPG on the
reflex and voluntary swallowing, some protective reflexes
could also operate according to the level of risk of aspiration
(Sasaki and Suzuki, 1967; Sasaki and Buckwalter, 1984;
Ertekin et al., 2001a; Altschuler, 2001). The pharyngeal
phase of swallowing may be controlled by the cortical
drives via medullary CPG in addition to triggering the
pharyngeal swallow. This is suggested from some clinical
studies. The involvement of the corticobulbar-pyramidal
fibers can cause dysphagia in which the relaxation and
opening of the CP muscle of the UES becomes abnormal,
especially in motor neuron disease and in suprabulbar palsy
due to multiple strokes (Ertekin et al., 2000b,c). This
suggests that descending excitatory and inhibitory drives
influence the pharyngeal phase of swallowing and trigger
and modulate the medullary pattern generator. The cortical
control of the pontomedullary CPG must have increased
phylogenetically and reached its maximum control in the
human.
5. Cerebral cortex and voluntary swallowing
Although the act of swallowing is thought to be
mediated principally by brain stem mechanisms (Jean,
2001) converging evidence from electrophysiological,
neuroimaging, and clinical studies indicates that the
cerebral cortex also plays a fundamental role in the regula-
tion of swallowing (Martin and Sessle, 1993; Miller, 1999).
In animal models, particularly the non-human primate,
studies employing cortical stimulation (Jean and Car, 1979;
Huang et al., 1989; Martin et al., 1997, 1999), ablation or
reversible inactivation of the cortex (Narita et al., 1999) and
cortical neuronal recordings (Martin et al., 1997; Yao et al.,
2001) have begun to delineate the detailed functional
organisation of the cortical swallowing representation
experimentally.
An individual can command the swallow voluntarily (i.e.
either food or saliva in his or her oral cavity). This fact
suggests that the medullary swallowing network can be
activated by cortical commands. On the other hand, a
normal human fetus can swallow by the 12th gestational
week, before the cortical and subcortical structures have
developed (Thexton and Crompton, 1998; Jean, 2001). It
has also been reported that swallowing is still possible in the
human anencephalic fetus (Thexton and Crompton, 1998;
Jean, 2001; Miller et al., 2003). Recent evidence indicates,
however, that the cerebral cortex plays an important role in
even the highly automatic type of swallowing in adult
humans (Hamdy et al., 1999a,b; Kern et al., 2001a; Martin
et al., 2001) as we discuss later.
Several clinical reports have indicated that cortical
dysfunction of any kind especially from the cerebro-
vascular disorders may result in dysphagia (Gordon et al.,
1987; Barer, 1989; Horner et al., 1990; Alberts et al., 1992;
Robbins et al., 1993; Smithard et al., 1997a,b; Daniels and
Foundas, 1997; Daniels et al., 1999; Smithard, 2002).
Indeed, in different studies, incidence of dysphagia in
conscious patients following stroke has been reported from
just below 30% (Young and Durant-Jones, 1990) to over
50% (Gordon et al., 1987) depending upon various factors.
Therefore, damage to the cerebral cortex can have a
significant effect upon the peripheral swallowing mechan-
ism operating at the brain stem level.
The concept of the cortical control of swallowing can be
drawn back to the studies of cerebral cortical stimulation in
humans, electrically to the open cortex by Penfield and co-
workers since 1937 (Penfield and Boldery, 1937; Penfield
and Rasmussen, 1950; Penfield and Jasper, 1954). Recently,
TMS to the human scalp suggests that swallowing is
represented within multiple cortical foci including the
lateral precentral and premotor cortices (Aziz et al., 1995,
1996; Hamdy et al., 1996, 1997a). It has also been possible
to stimulate the CP muscle of the UES by TMS of the cortex
(Ertekin et al., 2001b).
In healthy subjects, there is a somatotopic arrangement of
the various swallowing muscles in an asymmetrical
representation between the two hemispheres (Hamdy et al.,
1996). In stroke patients, damage to the hemisphere that has
the greater representation of swallowing corticospinal
output appears to predispose that individual to develop
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swallowing problems (Hamdy et al., 1996). The recovery of
swallowing function is associated with an enlargement of
the cortical representation in the undamaged hemisphere
suggesting that recovery depends on the presence of an
intact projection from the undamaged hemisphere that can
develop increased control over brain stem centers or CPG
over a period of weeks (Hamdy et al., 1997b, 1998a,b).
Unfortunately, information gathered using TMS refers only
to the projections from motor regions of the cortex to
swallowing muscles and not necessarily the cortical activity
associated with functional swallowing (Hamdy et al.,
1997a).
The recent advance in functional brain imaging including
functional MRI (fMRI) and PET studies now offers the
opportunity to examine the cortical representation of
swallowing in healthy humans (Hamdy et al., 1999a,b;
Mosier et al., 1999a; Zald and Pardo, 1999). Functional
studies of the human brain also indicate cortical involve-
ment in swallowing to be multifocal and bilaterally
represented. Most commonly cited of these foci include
those corresponding to areas in the sensory/motor cortex,
prefrontal cortex, anterior cingulate, insular (Hamdy et al.,
1999a,b; Mosier et al., 1999a; Zald and Pardo, 1999)
parietooccipital (Hamdy et al., 1999b; Zald and Pardo,
1999) and temporal (Hamdy et al., 1999a; Mosier et al.,
1999a; Mosier and Bereznaya, 2001; Martin et al., 2001)
regions.
Swallowing also produces areas of increased signal
change in the basal ganglia, thalamus, cerebellum and the
internal capsule (Mosier et al., 1999a; Mosier and
Bereznaya, 2001). Even with 1.5 T fMRI, the cranial nuclei
of pons and medulla and other nuclei of the lower brain stem
and cervical spinal cord might be localized in awake
humans with specific sensory stimulation or motor per-
formance (Komisaruk et al., 2002). The activation and role
of some cortical foci during swallowing can be discussed as
follows.
5.1. Lateral precentral gyrus
The caudolateral sensorimotor cortex is important in the
initiation of swallowing (Penfield and Boldery, 1937;
Hamdy et al., 1999a). This region of cortex is closely
linked to the control of tongue and face, so the presence of
swallowing activity in this region is not surprising (Corfield
et al., 1999; Kern et al., 2001b). In terms of the cortical
motor control of human swallowing, there might be two
distinct patterns of activity: first, the caudolateral motor
cortex which may be associated with the initiation of the full
swallowing sequence at the highest level and second, the
premotor regions which may be more modulatory and
concerned with “priming” the pharyngoesophageal com-
ponents of swallowing (Hamdy et al., 1999a).
As swallowing involves both hemispheres with large and
more intense activity present in the right hemisphere, the
motor/premotor areas have greater volume recruitment in
the right hemisphere in right-handed subjects (Kern et al.,
2001b) or with handedness independent hemisphericdominance (Hamdy et al., 1996; 1997a, 1999b).
5.2. Supplementary motor area (SMA)
The supplementary motor area (SMA) represented in the
superior and middle frontal gyri, is believed to be associated
with motor planning and, in particular, with planning of
sequential movements (Tanji et al., 1996) as occurs with
oropharyngeal swallowing. Therefore, SMA may play a
dynamic role in the execution of different swallowing tasks,
the activity of which may depend on the degree of difficulty
of the task (Mosier et al., 1999b).
5.3. Anterior cingulate cortex
Activation of this region during volitional swallowing
may reflect the attentional and/or affective component of the
swallowing task. Its activation with swallowing may also
reflect a role for this region in the mediation of visceromotor
activity such as digestive functions (Hamdy et al., 1999a,b;
Kern et al., 2001b).
5.4. Insula and frontal operculum
Insular function is thought to involve sensorimotor
integration, auditory and speech processing and effects on
cardiovascular rhythm (Augustine, 1996). In primates,
stimulation of the insula evokes swallowing, whereas
stimulation of the frontal operculum preferentially induces
mastication but at a higher stimulation level also evokes the
swallowing sequence (Martin et al., 1997, Martin and
Sessle, 1993).
In fact neuroimaging studies of representation of taste in
the human brain have found cortical areas activated to taste
such as the frontal operculum/insula and the orbitofrontal
cortex (Small et al., 1997, 1999; Zald et al., 2002;
O’Doherty et al., 2001).
Water, a substance that itself has a taste and is known to
activate neurons in the primate insular and orbitofrontal
taste cortices, is used as the cortical stimulus in swallowing
studies (Zald et al., 2002). Given this, important questions to
consider are how the taste of water and other foods and their
swallowing interact with each other and how we can
differentiate the cortical representation of taste from
swallowing. These problems need to be addressed in future
studies.
As it can be understood from above that swallowing is
associated with activation of the inferior frontal gyrus
corresponding to the inner face of the frontal operculum or
Brodmann’s area 44 on the cortical convexity adjacent to
the sylvian fissure in some subjects. Frontal operculum must
have contributions to swallowing because sensations of the
human mouth and pharynx have been partly localized to the
operculum (Penfield and Jasper, 1954). This area of cortex
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also may play a role in the control of non-speech orofacial
sensorimotor behaviours (Martin et al., 2001).
5.5. Somatosensory and parietal cortex
The swallowing tasks yield activation of the lateral
postcentral gyrus localized to Brodmann’s area 3, 2, 1
and/or 43. This finding of swallow-related activation of the
postcentral gyrus might reflect various types of orophar-
yngeal sensory processing and underscore the importance of
afferent information in the regulation of swallowing (Martin
et al., 2001). Cortical activation during both swallowing and
swallowing-related motor tasks that can be performed
independent of swallowing was also found in the parie-
tooccipital region corresponding to Brodmann’s areas 7, 9
and 31 (Kern et al., 2001b). Somatosensory and parietal
regions have been cited as a region of activity during
mechanical and chemical stimulation of the esophagus
(Furlong et al., 1998; Kern et al., 1998; Aziz et al., 1997,
2000) as well as during sensation of swallowing urge (Kern
et al., 2001b).
The somatosensory cortex and posterior parietal cortex
are likely to have a sensory role in the control of
swallowing. It might, therefore, be speculated that these
regions are utilized in the reception and higher processing of
sensation arising from the oropharynx and esophagus which
may then be linked to modulation of the motor activity via
connectivity with precentral cortex and insula (Hamdy et al.,
1999a; Aziz et al., 2000).
5.6. Temporal cortex
The swallow-related activation of the superior temporal
gyrus, corresponding to Brodmann’s areas 42/41 and 22/21
was found during water bolus swallow (Martin et al., 2001).
The temporal lobe has been implicated in a number of
functions that are related to swallowing. PET findings
suggest that the anteromedial temporal lobe is involved in
human taste quality recognition (Small et al., 1997). It can
be proposed that the temporal lobe activations reflect the
processing of the acoustic correlates of swallowing,
swallow-related sounds that are audible to the swallower,
by the auditory cortex (Martin et al., 2001). Another view is
that the temporal cortex together with the prefrontal cortex
could play a supplementary role in the regulation of
swallowing and feeding because of its relationship with
taste and imagery of food (Hamdy et al., 1999a).
The role of the subcortical structures including basal
ganglia, thalamus and cerebellum in the swallowing
function has not been clarified using neuroimaging methods,
however, clinical studies indicate that in some disorders of
the basal ganglia, dysphagia can be seen whereas in pure
cerebellar disorders, it is difficult to encounter swallowing
problems (Ertekin et al., 1998, 2002; Ertekin and Palmer,
2000; Ertekin, 2002).
5.7. Lateralization of cortical function in swallowing
Although human voluntary swallowing is represented
within a number of spatially and functionally distinct
cortical foci bilaterally, these regions may be activated
differently by volitional swallowing. There is a kind of
lateralization between hemispheres in the regulation of
swallowing (Martin et al., 2001; Mosier et al., 1999b;
Kern et al., 2001a). Especially during swallowing, the
sensorimotor cortex is organised bilaterally but display
interhemispheric asymmetry independent of handedness
(Hamdy et al., 1996). The hemispheric lateralization has
been reported in the right hemisphere or the left
hemisphere without a consistent pattern of lateralization
from the sensorimotor cortices (Hamdy et al., 1996).
Lateralization to the right hemisphere tends to be greater
than that in the left hemisphere (Mosier et al., 1999b;
Martin et al., 2001) while the activity was found to be
dominant for one hemisphere with left hemispheric
dominance more prevalent among normal healthy sub-
jects (Mosier et al., 1999b). Why the right hemisphere
shows stronger lateralization is unclear and remains to be
determined.
Swallowing is a phylogenetically old physiological
function. In an investigation of functional brain asym-
metry during childhood, it was shown that human infants
are right-hemisphere dominant up to the age of 3 years at
which point an asymmetric shift to the left occurs
(Chiron et al., 1997). It can be speculated that stronger
lateralization in the right hemisphere during the swallow-
ing task may represent a primal cortical organisational
structure (Mosier et al., 1999b).
Activation of the insula was found to be lateralized to
the right hemisphere in right-handed subjects for
voluntary saliva swallow, suggesting a functional hemi-
spheric dominance of the insula for the processing of
swallowing, salivation and gustatory functions (Zald and
Pardo, 1999; Small et al., 1999). The development of
dysphagia in human subjects was reported as a result of
damage to the right anterior insular region (Hamdy et al.,
1997b; Daniels and Foundas, 1997).
It is likely that the alternate hemispheric lateralization
may reflect a cortical organisation scheme for swallowing
that facilitates the diverse neuromuscular demands of
different swallowing tasks (Mosier et al., 1999b). Further
examination of the role of hemispheric lateralization in the
cortical control of swallowing and its implications for
normal and abnormal swallowing is necessary.
5.8. Volitional versus reflexive swallowingin cortical
regulation
It has been reported that reflexive or automatic swallows
are represented in the sensorimotor cortex and that
volitional swallow (or voluntarily initiated swallow) is
represented in multiple cortical regions including
C. Ertekin, I. Aydogdu / Clinical Neurophysiology 114 (2003) 2226–22442238
the primary sensorimotor cortex. The total volume activity
during volitional swallowing is significantly larger than that
during reflexive swallows in either hemisphere. For the
reflex swallow, there is a significant larger left hemispheric
volume compared with the right hemisphere (Kern et al.,
2001a). In another report, the automatic (naive) swallowing
of saliva or other highly automatic types of swallowing were
also demonstrated to activate the cerebral cortex (Martin
et al., 2001). The fact that area M1 (precentral cortex) is
activated in over 80% of human subjects in association with
the automatic saliva swallows is of particular interest, given
that this cortical region is classically considered to be
involved in voluntary movement execution. Automatic
swallowing produced activation within several other
common cortical regions: lateral postcentral gyrus and
right insula (Martin et al., 2001).
The signal changes in fMRI peak some 9–12 s after the
swallow. This may indicate that in swallowing, the time
course of associated neuronal activity is prolonged (Hamdy
et al., 1999a). This may be related to all of the processes of
swallowing from oral, pharyngeal and esophageal phases.
This long-lasting event incorporates secondary motor
activity in the esophagus and continual modulatory ascend-
ing sensory input with descending motor output (Hamdy
et al., 1999a), however, whether this phenomenon occurs in
reflexive swallowing remains to be clarified in future
neuroimaging studies.
5.9. How the cortex works with multiple foci during
swallowing
The fact that volitional swallowing is represented in
multiple cortical regions can simply be explained by the
sensory inputs (i.e. tactile, gustatory) coming from the
oropharyngeal and esophageal inner surfaces which activate
the sensorimotor cortex, posterior parietal, anterior insula,
and temporal cortex and the motor output being initiated
from the precentral and lateral motor cortex. Other regions
might be related with the emotional and attentional aspects
of swallowing such as the anterior cingulate cortex. All non-
sensorimotor regions of the cerebral loci may be related
with swallow-related intent and planning and possible urge
(Kern et al., 2001a). Such an explanation for the multiple
cortical foci during swallowing may favor a singular,
hierarchical model from multiple sensory inputs to the
single motor output to and from the cortex descending
through the CPG of the pontobulbar region.
Involvement of many different cortical sites, on the
other hand, also suggests that the control of swallowing
may be organised differently from that suggested by the
hierarchical projection system (Bass, 1997; Mosier and
Bereznaya, 2001). It has been hypothesized that there are
two separate, serial pathways from the sensorimotor cortex
or insula to thalamus. Organisation of the control of
voluntary repetitive swallowing into two parallel systems
may confer the ability to effectively coordinate and
integrate this highly complex, sequentially based motor
behaviour. It is suggested that the cortical organisational
scheme for swallowing may incorporate a functional
structure that supersedes the anatomical structure, in
which each functional unit or module, performs a specific
role in sensorimotor planning and execution (Bass, 1997;
Mosier and Bereznaya, 2001). We will have to wait for
further studies for a clearer understanding of the inter-
actions of several cortical foci during swallowing.
5.10. Clinical implications
The fact that cortical representation of swallowing is
multifocal and bilateral may lead to two concepts:
1. The extent of cortical and subcortical representation
could explain why so many neurological conditions
produce dysphagia (Zald and Pardo, 1999; Kern et al.,
2001a).
2. The same physiological phenomena help to describe
the critical role for the intact hemisphere reorganis-
ation in recovery from dysphagia in stroke, because
the return of swallowing is associated with increased
pharyngeal representation in the unaffected hemisphere
(Hamdy et al., 1997b, 1998b). The organisation of the
healthy human swallowing motor cortex can be altered
in a sustained manner after electrical sensory stimu-
lation of the pharynx (Hamdy et al., 1998b). Sensory
driven reorganisation of human motor cortex is highly
dependent upon the frequency, intensity, and duration
of stimulus applied. Those patterns of input associated
with enhanced excitability (5 Hz, 75% maximal
tolerated intensity for 10 min) induce stronger cortical
activation to fMRI. When applied to acutely dyspha-
gic stroke patients, swallowing corticobulbar excit-
ability is increased mainly in the undamaged
hemisphere, being strongly correlated with an
improvement in swallowing function. Thus, input to
human adult brain can be programmed to promote
beneficial changes in neuroplasticity and function after
cerebral injury (Fraser et al., 2002; Siebner and
Rothwell, 2003; Hamdy et al., 2002).
A role for fMRI in examining cortical and subcortical
functions in abnormal swallowing should be necessary for
future studies. Having established a normal database, fMRI
may prove an adjunctive technique to conventional MR
imaging in the investigation of dysphagia following cerebral
injury, insult and disease. Also, the temporal relationship
between activation in the swallowing CPG in the ponto-
bulbar region and the primary somatosensory cortex
remains to be elucidated and is a subject for future
investigation.
C. Ertekin, I. Aydogdu / Clinical Neurophysiology 114 (2003) 2226–2244 2239
6. Conclusions
Swallowing is subdivided into 3 phases: oral, pharyngeal
and, esophageal phases. The oral cavity, pharynx, and
larynx are anatomically separated but functionally inte-
grated for the complex and sequential motor responses that
include chewing, swallowing and speech. From the point of
swallowing, the oral and pharyngeal phases are highly
interrelated and the term oropharyngeal swallowing is often
used. Despite this, the oral phase is often accepted as
voluntary, while the pharyngeal phase is considered a reflex
response. Apart from the chewing and taste functions, the
oral phase is primarily related with the oral preparation and
the triggering to the pharyngeal phase of swallowing.
Sensory inputs arising from posterior oral, pharyngeal and
some laryngeal mucosae and transmitted to the medullary
NTS and the cerebral cortex are necessary for the triggering
of the bolus in the oropharyngeal region. Once swallowing
is initiated, the cascade of the sequential muscle activation
does not essentially alter from the perioral muscles down-
ward. The main events are the transport of the food safely to
pharyngoesophageal segment by the activation of the
tongue, submental/suprahyoid muscles and pharyngeal
constrictor muscles and the relaxation and opening the CP
sphincter muscle. During the food transport, the airway is
protected and closed by several laryngeal muscles and the
larynx is pulled up.
The sequential and orderly activity of swallowing
muscles can be demonstrated by EMG methods. Submen-
tal/suprahyoid muscles are easily recorded by surface
electrodes and demonstrate the onset and complete duration
of the oropharyngeal phase of swallowing. Laryngeal and
pharyngeal muscles are approached by needle electrodes or
by means of intraluminar catheter electrodes. The CP
muscle of the UES is tonically active during rest and the
tonic activity ceases during a swallow.
Some premotor neurons or interneurons are found in the
bulbar reticular formation, which can initiate or organisethe swallowing motor neurons. Their network is known as
the CPG. These neurons are located in and around the NTS
and around the NA of the ventrolateral medulla oblongata.
The premotor neurons in and around NTS contain the
generator neurons involved in the triggering, shaping and
timing of the sequential swallowing pattern. The premotor
neurons around the NA contain the switching neurons which
distribute the swallowing drive to the various pools of the
motoneurons involved in swallowing (V, VII, IX, X, XII
cranial motoneurons). Anatomical connections mediated by
nerve fibers crossing the midline exist between the two
medullary regions where the swallowing neurons are
located in and around the NTS and NA.
The descending excitatory and inhibitory drives from the
cortex and subcortex influence the oropharyngeal swallow-
ing and trigger and modulate the CPG. The cortical control
of CPG must have increased phylogenetically and reached
its maximum control in the humans.
The recent advance in the functional brain imaging
including fMRI and PET image studies now offer the
opportunity to examine the cortical representation of
swallowing in human. These studies indicate that cortical
involvement in swallowing is multifocal and bilaterally
represented. Most commonly cited of these foci include
those corresponding to areas in the sensory/motor cortex,
prefrontal cortex, anterior cingulate, insular, opercular,
parietooccipital, and temporal regions. Swallowing also
produces areas of increased signal change in the basal
ganglia, thalamus, and cerebellum.
Although human voluntary swallowing is represented
bilaterally, there is interhemispheric asymmetry indepen-
dent of handedness. Lateralization to the right hemisphere
tends to be greater than that in the left hemisphere. Insular
cortex is found to lateralize to the right hemisphere in right-
handed subjects for voluntary saliva swallows. It has also
been reported that reflexive or automatic swallows are
represented in the primary sensorimotor cortex and in
several other common cortical regions.
Such functional neuroimaging and TMS studies may lead
some concepts. First of all, the extent of cortical and
subcortical representation explains why so many cortical
and subcortical neurological conditions produce dysphagia.
Second, the same findings help to describe the critical role
for the intact hemisphere reorganisation in recovery from
dysphagia in stroke, as the return of swallowing is
associated with increased pharyngeal representation in the
unaffected hemisphere.
There are also various possibilities for the treatment of
dysphagia given the multiple and bilateral representation of
swallowing in the cortex, including the increase of sensory
inputs (i.e. electrical) to the cerebral cortex to promote
beneficial changes towards cortical plasticity.
Acknowledgements
This work has been supported in part by the Turkish
Academy of Sciences.
We are also grateful for the cooperation of our co-
workers, especially Murat Pehlivan, MD, Nur Yüceyar,
MD, Nefati Kıylıoglu, MD, Sultan Tarlaci, MD, Yaprak
Secil, MD. We thank Nilüfer Ertekin-Taner MD, PhD, who
reviewed the English text.
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