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Clinical Neurophysiology 112 (2001) 86±94

Cricopharyngeal sphincter muscle responses to transcranial magnetic

stimulation in normal subjects and in patients with dysphagia
Cumhur Ertekin a,b,*, BuÈlent Turman c, Sultan Tarlaci a, MuÈnevver Celik d, Ibrahim Aydogdu a,b,
Yaprak Secil a, Nefati Kiylioglu a
Department of Neurology, Medical School Hospital, Ege University, TR 35100 Bornova, Izmir, Turkey
Clinical Neurophysiology, Medical School Hospital, Ege University, TR 35100 Bornova, Izmir, Turkey
Department of Biomedical Sciences, University of Sydney, Sydney, Australia
Department of Neurology, Sisli Etfal Hospital, Istanbul, Turkey
Accepted 3 October 2000

Objective: Cricopharyngeal (CP) muscle of the upper oesophageal sphincter (UES) has a signi®cant role in the pharyngo-esophageal
phase of deglutition. The linkage between the CP muscle of UES and the motor cortex has not been previously studied electrophysiologically
in healthy humans and in patients with neurogenic dysphagia.
Methods: Needle recordings of EMG responses were carried out from the CP sphincter muscle following transcranial magnetic stimula-
tion (TMS) over the vertex around the Cz electrode position (cortical MEP), and on the parieto-occipital skull and the occiput ipsilaterally
(peripheral MEP) in 14 healthy control subjects and in 26 patients with and without neurogenic dysphagia. Needle recordings obtained from
the cricothyroid muscle of the larynx were also evaluated in six healthy subjects.
Results: The cortical motor latency of CP sphincter muscle was 10.7 ^ 0.5 ms with an amplitude of 0.8 ^ 0.2 mV in healthy subjects.
Both the latency and amplitude of CP-MEP were facilitated during swallowing. The peripheral MEP of the CP muscle was very stable in all
normal subjects (5.1 ^ 0.3 ms; 1.3 ^ 0.3 mV) and swallowing did not in¯uence these parameters. The cortically elicited CP-MEP was
signi®cantly longer than the cortical MEPs obtained from the cricothyroid muscle of the larynx. In 10 dysphagic patients with corticobulbar
tract involvement (6 ALS and 4 pseudobulbar palsy) and with pathologic and hyperre¯exic EMG of the CP-sphincter muscle, the cortical
MEP of CP muscle of the upper esophageal sphincter could not be elicited, although the peripheral CP-MEPs were obtained. TMS never
produced a swallowing movement in neither healthy subjects nor patients.
Conclusion: The CP muscle of the upper esophageal sphincter can produce MEPs by cortical TMS and by stimulation at the root/nerve
levels of vagus nerve. The MEP latency values and central motor delay suggest that there is an oligosynaptic corticobulbar pathway to the
motoneurons of CP muscles. When the pathway is affected by a pathology (i.e. ALS or pseudobulbar palsy) the CP sphincter becomes
hyperre¯exic due to disinhibition and the cortical MEP of the CP muscle disappears due to degeneration of the corticobulbar pathway. These
mechanisms appear to be responsible for the pathogenesis of dysphagia. q 2001 Elsevier Science Ireland Ltd. All rights reserved.
Keywords: Transcranial magnetic stimulation; Cricopharyngeus muscle; Upper oesophageal sphincter; Corticobulbar tract; Dysphagia

1. Introduction particularly, the facial muscles (Schriefer et al., 1988; Bene-

cke et al., 1988; RoÈssler et al., 1989; Cruccu et al., 1990;
Transcranial magnetic stimulation (TMS) of the human Ghezzi et al., 1992; Cocito et al., 1993; Meyer et al., 1994;
motor cortex is generally accepted as a useful neurophysio- Campos et al., 1995; Urban et al., 1997), the lingual muscles
logical tool that permits non-invasive examination of central (Muellbacher et al., 1994; Urban et al., 1996; Meyer et al.,
motor pathways. Descending motor pathways and the corti- 1997; Ghezzi and Baldini, 1998), the masticatory muscles
cal representation of the distal limb muscles have been (Cruccu et al., 1989; Pavesi et al., 1991), the sternocleido-
extensively studied (Rossini et al., 1994). Since its introduc- mastoid muscles (Benecke et al., 1988; Benecke and Meyer,
tion in the late 1980s, TMS has been used to explore the 1991; Berardelli et al., 1991; Odergren and RimpilaÈinen,
motor organisation of the cranial musculature. Until now, 1996; Odergren et al., 1997) and the laryngeal muscles
(Thumfart et al., 1992) have been investigated in various
* Corresponding author. Tel.: 190-232-422-0160; fax: 190-232-463- studies.
0074. Recently, motor evoked potentials (MEPs) have been
1388-2457/01/$ - see front matter q 2001 Elsevier Science Ireland Ltd. All rights reserved. CLINPH 2000504
PII: S13 88-2457(00)0050 4-6
C. Ertekin et al. / Clinical Neurophysiology 112 (2001) 86±94 87

elicited from the pharyngeal and esophageal striated as the criteria for correct electrode penetration into the CP
muscles by means of an intraluminar-pharyngo-esophageal muscle (Ertekõn et al., 1995, 1996). The needle electrode
catheter inserted transorally (Hamdy et al., 1996; Aziz et al., was inserted while the subject was in a recumbent position
1994, 1995, 1996). In these studies, the esophageal electro- with the head tilted slightly posteriorly. After a few minutes,
des were positioned 3 cm below the upper esophageal the subject was moved to a sitting position for the investiga-
sphincter's (UES) lower margin. On the other hand, the tion. In any case, if coughing occurred or the patient experi-
UES, particularly the cricopharyngeal (CP) sphincter enced an unpleasant feeling or pain the needle electrode was
muscle of UES, is very important in the core of oropharyn- immediately removed.
geal function in normal subjects (Ertekõn et al., 1995; Erte- In 6 healthy subjects (4 males and two females) the
kõn, 1996) and in patients with neurogenic dysphagia cricothyroid muscle (CT muscle) of the larynx was also
(Ertekõn et al., 1998). Therefore, there is a need to under- investigated using a needle electrode of the same kind
stand in detail how the cricopharyngeal CP sphincter muscle inserted percutaneously. Once the electrode was inserted it
of the UES is linked with the motor cortex. was passed through the cricothyroid ligament about 0.3 cm
We investigated the link between the CP sphincter muscle lateral to the midline and then directed laterally and poster-
and motor cortex by recording the activity of the CP sphinc- iorly. The veri®cation of cricothyroid muscle insertion was
ter muscle (Ertekõn et al., 1995) in response to TMS in provided by the observation of intense EMG burst in the CT
healthy control subjects and neurological patients with and muscle during phonation of `aa, ee and ii' (Schaefer, 1991;
without dysphagia using a concentric needle electrode Yin et al., 1997). In addition, swallowing also activated the
inserted percutaneously. CT muscle. Following a successful insertion into the CT
muscle, the subject was seated at a 708 angle, and the
back and neck were supported by a soft pillow. As in the
2. Materials and methods case of the recording from the CP sphincter muscle, the
subject was instructed to sustain his/her head in this posi-
Fourteen healthy volunteers with a mean age of 43.2 tion. Both the CT and CP muscles were investigated during
years (range 17±73 years, 5 females and 9 males) partici- the same session, but not simultaneously. The MEPs
pated in the study. In the patient group there were 26 obtained from the CT muscle were analysed and compared
patients with an age range of 34±72 years. The age, gender with MEPs obtained from the CP sphincter muscle.
and clinical diagnosis of patients are documented in Table 1. In patients and in healthy subjects, the `normal' CP
The clinical diagnosis of the patients was supported by sphincter EMG had to exhibit the following features:
imaging methods (MRI or CT scan) and electromyography
(EMG). Ten patients had no clinically manifested dyspha- 1. A high frequency tonic EMG activity that resembled an
gia, nor did they show any electrophysiological abnormal- interference pattern and occurred at rest with an ampli-
ities in swallowing studies, including direct EMG tude of at least 50 mV had to be observed clearly.
recordings from the CP sphincter muscle (Ertekõn et al., 2. The tonic activity had to switch off during 3-ml water
1995, 1998). In the remaining 16 patients, dysphagia was swallows and induce a silent period of no less than 300
clinically and electrophysiologically apparent; however, the ms (range 300±600 ms).
CP sphincter EMG was not necessarily abnormal, except in 3. The commencement and end of CP sphincter EMG pause
patients with amyotrophic lateral sclerosis (ALS) and pseu- had to occur in coordination with the laryngeal upward/
dobulbar palsy with vascular or degenerative nature (Table downward movements con®rmed by the laryngeal move-
1). The study was approved by the Ethics Committee of our ment sensor (Ertekõn et al., 1995).
University Hospital and informed consent was obtained
from all healthy subjects and patients.
An abnormal CP sphincter EMG was referred to as `hyper-
During the assessment procedure, initially the EMG
re¯exic CP EMG' and considered if the following criteria
activity of the CP sphincter muscle was recorded by
were encountered in patients:
means of concentric needle electrodes (Medelec disposable
needle electrode, DMC-37, diameter 0.46 mm, recording
area 0.07 mm 2). The needle electrode was inserted through 1. The CP-EMG pause period had to be less than 300 ms.
the skin at the level of the cricoid cartilage about 1.5 cm 2. The CP-EMG pause had to show signs of incoordination,
lateral to its palpable lateral border in the posteromedial especially as a result of the premature closure of the CP
direction. As the electrode penetrated the muscle a high sphincter long before the descending movement of the
frequency tonic EMG activity could be observed on the larynx.
oscilloscopic screen of the EMG apparatus (Medelec 3. During swallowing, the CP-EMG pause period had to be
Mystro MS-20). During a swallow, this tonic activity disap- interrupted by unexpected EMG bursts (Ertekõn et al.,
peared for a brief period of time (400±600 ms). The pause in 1998, 2000).
EMG activity during a swallow together with the increased
tonic activity prior to and following the pause period served On the basis of these criteria the CP sphincter EMG record-

Table 1
MEPs recorded from the CP sphincter muscle of patients with/without dysphagia a

Patient Age (years)/sex Clinical diagnosis Clinical signs of dysphagia CP sphincter EMG Cortical stimulation Peripheral stimulation

Latency (ms) Amplitude (mV) Latency (ms) Amplitude (mV) Central delay (ms)

1. S.T. 40, Male Con My No Normal 10.0 0.7 4.0 1.0 6.0
2. B.B. 39, Male Con My No Normal 12.6 0.3 6.5 0.7 6.1
3. F.G. 29, Male My Dys No Normal 9.7 0.6 3.5 0.8 6.2
4. A.Z. 36, Female My Dys Yes Normal 8.8 0.1 3.9 0.5 4.9
5. E.E. 35, Male Tracheostomy b No Normal 13.0 0.6 7.0 0.5 6.0
6. T.S. 55, Male EPS Yes Normal 10.0 0.3 4.0 2.0 6.0
7. S.K. 52, Male Cervical dystonia Yes Normal 12.0 0.8 7.0 0.9 5.0
8. M.B. 34, Male Spastic dysphonia No Normal 13.0 1.0 5.0 2.5 8.0
9. M.G. 65, Male Spastic dysphonia No Normal 12.0 0.5 4.0 1.5 8.0
10. A.E. 64, Male Parkinson's disease No Normal 8.9 0.3 3.9 1.8 5.0
11. O
È .O
È. 67, Male Parkinson's disease Yes Normal 13.0 0.8 Not Tested ±
12. N.S. 64, Female PSP No Normal 10.0 0.4 3.6 1.2 6.4
13. F.OÈ. 68, Female PSP Yes Pathologic No Response 4.0 0.6 ±
14. M.B. 64, Male PBP No Normal 14.0 0.4 5.0 0.2 9.0
15. F.UÈ. 59, Female PBP Yes Normal 12.0 0.4 4.0 0.4 8.0
16. E.Y. 61, Male PBP 1 PNP Yes Pathologic No Response 11.7 1.0 ±
17. S.G. 59, Female PBP Yes Pathologic No Response 3.0 1.6 ±
18. M.U. 67, Male PBP Yes Pathologic No Response 5.0 2.0 ±
19. R.S. 49, Male ALS No Normal 13.0 0.3 6.0 0.8 7.0
20. Y.K. 63, Male ALS Yes Normal 11.0 0.3 5.0 0.5 6.0
21. S.B. 65, Female ALS Yes Pathologic No Response 3.5 0.5 ±
C. Ertekin et al. / Clinical Neurophysiology 112 (2001) 86±94

22. S.UÈ. 53, Female ALS Yes Pathologic No Response 8.0 1.5 ±
23. A.OÈ. 43, Male ALS Yes Pathologic No Response 7.0 2.0 ±
24. M.A. 48, Male ALS Yes Pathologic No Response 6.0 0.2 ±
25. O.CË. 68, Male ALS Yes Pathologic No Response 3.0 1.5 ±
26. H.A. 72, Male ALS Yes Pathologic No Response 4.3 3.5 ±
My Dys, myotonic dystrophy; Con My, congenital myotonia; EPS, extrapyramidal syndrome; PBP, pseudobulbar palsy; PNP, polyneuropathy; ALS, amyotrophic lateral sclerosis; PSP, progressive
supranuclear palsy; M, male; F, female.
Head trauma with tracheostomy scar
C. Ertekin et al. / Clinical Neurophysiology 112 (2001) 86±94 89

ings of patients obtained in response to TMS were compared

with results obtained from the healthy control group.
The motor cortex was stimulated with a round magnetic
coil (9 cm in diameter) connected to the magnetic stimulator
(Novametrix Magstim 200, 2 Tesla version; Whitland,
Dyfed, Wales, UK) and the stimulator output intensity
used was 50% above the threshold intensity that evoked
MEPs. Stimulation was performed over the Cz electrode
position, 2 cm anterior and 4±8 cm lateral to the Cz point
over both hemispheres separately. The needle electrode was
inserted into the CP and CT muscles of the left side. For
stimulation of the left hemisphere the current direction was
counterclockwise. Once the scalp location with the lowest
stimulation threshold to evoke a MEP response was de®ned,
an experimenter held the stimulator coil in that ®xed posi-
tion. In addition to cortical stimulation (cortical MEP), the
parieto occipital skull and occiput were also stimulated Fig. 1. CP sphincter muscle MEPs obtained from a normal subject. (A)
bilaterally in all subjects (peripheral MEP). The magnetic Magnetic stimulation was applied over the vertex around the Cz electrode
shocks were given in resting tonic condition of CP but it was position (cortical stimulation); (B) the parieto-occipital skull region ipsi-
lateral to the recording site was stimulated (peripheral stimulation). Note
necessary to stimulate during swallowing in some subjects. the different time base for (A) and (B). In each trace two responses were
The TMS were delivered directly after the onset of the superimposed.
rebound activity period of the swallowing pattern of CP
sphincter on hearing typical sounds of CP-EMG.
For each location of stimulation, at least 10 sweeps were the onset latencies appeared to be more stable. Magnetic
recorded and in a given condition the average onset and stimulation of other anterior cortical regions 4 cm or more
amplitude of the response was calculated by taking into
account 5 of the MEP records with the shortest onset laten-
cies. The intervals between magnetic stimuli during swal-
lowing were not less than 20±30 s. After a swallow the
subjects were given suf®cient time (20±30 s) before another
swallow and therefore the interstimulus interval of TMS
was related to the interval between swallows. The sweep
time was set to 20, 50 or 100 ms and the frequency band-
width was 50±500 kHz, at the limits of the EMG recording

3. Results

3.1. Normal subjects

Of the 14 healthy subjects, the TMS of the motor cortex

was capable of evoking a clear-cut MEP from the CP
sphincter muscle of the UES in all but one subject. Fig. 1
shows the CP muscle MEPs obtained in response to
magnetic stimulation over the fronto-parietal vertex (upper
trace, A) and the ipsilateral parieto-occipital skull (lower
trace, B). Vertex stimulation around the Cz electrode posi-
tion or slightly contralateral to it almost always produced a
CP-MEP with a mean latency of 10.7 ^ 0.5 ms (mean ^
SEM) (ranging between 8.0 and 14.0 ms). The average
amplitude of CP-MEP was 0.8 ^ 0.2 mV and varied
between 0.15 and 1.9 mV. However, as can be seen from
Fig. 2. Twelve successive CP sphincter muscle MEPs elicited in response to
individual consecutive traces plotted in Fig. 2, there was TMS over the vertex from a healthy subject. All 12 sweeps were super-
substantial variation in the amplitude of CP-MEPs from imposed at the bottom trace. Note the considerable variations in the ampli-
one stimulus to the next. In contrast, in a given subject, tude of MEPs.
90 C. Ertekin et al. / Clinical Neurophysiology 112 (2001) 86±94

lateral to midline on the ipsilateral and contralateral hemi- latency to the onset and the peak of the negative wave in
spheres often failed to evoke a response from the CP all CP-MEPs recorded. None of the magnetic stimuli
muscle. In one healthy subject attempts to evoke a cortical applied to any of the cortical locations ever produced any
MEP have consistently failed although MEPs could easily silent periods in the CP muscle EMG, and furthermore,
be elicited from ipsilateral parieto-occipital skull region there were no indications of any CP sphincter EMG activity
stimulation. that resembled a swallowing pattern.
The lower traces in Fig. 1 were obtained from stimulation In 6 subjects, the MEPs obtained from the CP muscle of
of the parieto-occipital skull region ipsilateral to the CP UES were compared with the MEPs elicited from the CT
muscle studied. These MEPs were consistent with regard muscle of larynx. The CT muscle MEPs could be maximally
to their shape, amplitude and latency, and furthermore, elicited by stimulation of the contralateral hemisphere 4±6
their thresholds were lower (about 30±40%) than the thresh- cm lateral to the vertex. Fig. 4 shows the consecutive CT
olds of CP-MEPs obtained from stimulation of the fronto- muscle MEP traces plotted in response to TMS. As can be
parietal vertex (mean threshold was 61%). Their mean seen from individual traces, the cortical MEPs of CT muscle
latency of 5.1 ^ 0.3 ms (range 4.0±6.5 ms) was shorter were also variable from stimulus to stimulus. In addition,
and the mean amplitude of 1.3 ^ 0.3 mV (range 0.5±3.5 magnetic stimulation evoked some late responses from the
mV) was higher than those of cortical MEPs. Since the CT muscle (Fig. 4). In all subjects studied, a facilitatory
features of MEPs recorded from stimulation of the ipsilat- activity such as phonation or swallowing was essential to
eral parieto-occipital or occiput region were similar to evoke an unequivocal response from the CT muscle. The
recordings obtained from root or nerve stimulation of onset latencies of cortical CT-MEPs were often shorter than
cranial muscles, these MEPs (referred to as `peripheral those of CP-MEPs, on average 8.4 ms and ranged from 6.9
MEPs') were accepted as being evoked from motor root/ to 10.0 ms (Table 2). The mean latency difference among 6
proximal nerve stimulation of the vagus either intra- or subjects was 2.1 ms shorter for CT muscle MEPs than for
extracranially. Consequently, the mean central motor CP muscle MEPs and ranged from 0.1 to 6.0 ms. The mean
latency to the CP sphincter muscle was calculated to be amplitude of cortical CT-MEPs were comparably similar to
5.5 ^ 0.4 ms and ranged between 4.0 and 8.0 ms.
Investigation of CP muscle MEPs during swallowing
revealed that the cortical MEPs evoked in response to vertex
stimulation were clearly facilitated by the swallowing
movement. Fig. 3 shows the cortical MEPs obtained at
rest (traces in B) and when the subject was performing a
swallow (traces in C). During swallowing there was a
substantial increase in the amplitude of cortical MEPs. In
addition, swallowing produced a slight decrease in the

Fig. 3. The CP sphincter muscle MEPs obtained from a healthy subject. The
superimposed traces were collected. (A) In response to magnetic stimula-
tion of the parieto-occipital skull region during resting condition (peripheral Fig. 4. The laryngeal cricothyroid muscle MEPs obtained from a healthy
MEPs); (B) from stimulation over the vertex at rest; (C) by vertex stimula- control subject in response to TMS of the contralateral hemisphere (more
tion during swallowing. Note the facilitation of cortical MEPs during the than 4 cm lateral to the vertex). Twelve consecutive responses were super-
swallowing movement. (D) Stimulation over parieto-occipital skull region imposed at the bottom of the ®gure. Note the late re¯ex responses that
during swallowing. occurred following the CT-MEP (compare with CP-MEP traces in Fig. 2).
Table 2
Comparison of MEPs recorded from cricopharyngeus (CP) and cricothyroid (CT) muscles

Subject Age (years)/sex CP-MEP cortical CT-MEP cortical CP-MEP peripheral CT-MEP peripheral Central motor delay

Latency (ms) Amplitude (mV) Latency (ms) Amplitude (mV) Latency (ms) Amplitude (mV) Latency (ms) Amplitude (mV) CP (ms) CT (ms)

1. H.D. 38, Male 11.1 1.9 7.0 2.5 6.5 1.0 3.0 3.0 4.6 4.0
2. G.D. 56, Female 10.0 1.6 6.9 1.0 6.0 2.5 3.0 0.9 4.0 3.9
3. M.B. 34, Male 13.0 1.0 7.0 0.7 5.0 2.5 4.2 1.5 8.0 2.8
4. N.E. 53, Female 11.2 0.3 9.8 0.6 NT a NT 5.0 0.5 ± 4.8
5. M.G. 65, Male 12.0 0.5 10.0 0.8 NT NT NT NT ± ±
6. O.G. 36, Male 9.9 0.3 10.0 0.4 4.0 0.5 4.0 2.0 5.9 6.0
Mean ^ SEM 11.2 ^ 0.5 0.9 ^ 0.3 8.4 ^ 0.7 1.0 ^ 0.3 5.3 ^ 0.6 0.6 ^ 0.5 3.8 ^ 0.4 1.58 ^ 0.4 5.6 ^ 0.8 4.3 ^ 0.5
NT, not tested.
C. Ertekin et al. / Clinical Neurophysiology 112 (2001) 86±94
92 C. Ertekin et al. / Clinical Neurophysiology 112 (2001) 86±94

the mean amplitude of CP-MEPs, 1.0 ^ 0.3 and 0.9 ^ 0.3 meters. Although two of these patients were dysphagic, all 5
mV, respectively. patients displayed normal CP sphincter EMG features. If the
As in the case of CP-MEPs, short latency MEPs of CT dysphagic patients had an abnormal, i.e. hyperre¯exic CP
muscle were also obtained from stimulation of the parieto- sphincter EMG activity, then the cortically evoked motor
occipital skull region ipsilateral to the needle recording site. potentials could not be obtained.
The mean latency of these stable proximal motor nerve
responses was also shorter in comparison to CP-MEP laten-
cies (Table 2). Accordingly, the central motor latency was 4. Discussion
similarly shorter for CT-MEPs compared to those of CP-
MEPs (4.3 vs. 5.6 ms mean values). TMS over the vertex around `Cz' or over a slightly lateral
region contralateral to the CP sphincter muscle needle
3.2. Patients recording site produced the largest MEPs and is therefore
likely to be the only focus for cortical stimulation of the CP
Of the 26 patients investigated, 11 had muscle disorders sphincter muscle of UES. The CP sphincter muscle should
with myotonia and/or movement disorders, and regardless be somatotopically represented on the motor and premotor
of a complaint of dysphagia, the long latency cortical and cortices of both hemispheres. However, the dif®culty to
short latency peripheral MEPs were easily obtained within evoke the CP-MEPs in response to isolated stimulations of
the range of normal limits (Table 1). Moreover, their CP the contralateral and ipsilateral hemispheres in our study
sphincter EMG responses were recorded as normal during was somewhat puzzling. Although Hamdy et al. (1996)
both resting and swallowing periods. The remaining 15 reported that the muscles involved in human swallowing
patients shared the common clinical signs and symptoms function, including the proximal esophageal striated
of pseudobulbar palsy. There were two important different muscles, are represented bilaterally on the motor cortex,
®ndings observed in these patients: our attempts to evoke a response from the CP muscle by
stimulation of the lateral regions of the motor cortical strip
1. The cortical CP-MEP was absent in 10 of 15 patients. were unsuccessful. For this discrepancy, at present, we can
2. However, the peripheral CP-MEPs obtained by stimula- only propose that the threshold for activation of the CP
tion of the parieto-occipital skull region were relatively muscle is relatively high, and therefore, only bilateral stimu-
easily elicited in all these patients (Fig. 5).
lation of the CP sphincter related cortical regions of both
hemispheres by vertex stimulation would be enough to
In all patients with absent cortical CP-MEP, the CP sphinc-
evoke the MEPs. Bilateral cortical representation has also
ter EMG was abnormal and became hyperre¯exic during
been described for the external anal sphincter, which is like-
swallowing. Ten patients who had these abnormal electro-
wise maximally stimulated around the vertex (Ertekõn et al.,
physiological features were unequivocally dysphagic (Table
1990; Herdmann et al., 1991; Turnbull et al., 1994),
although its representation in the parasaggital region is
In 5 patients with suprabulbar palsy due to ALS (two
closer to vertex.
patients), multiple lacunar infarctions (two patients) and
Another argument for the bilateral cortical representation
progressive supranuclear palsy (one patient), both the corti-
of the CP muscle is associated with its anatomical location.
cal and peripheral MEPs obtained were within normal para-
Since the CP striated muscle is a sphincter muscle, the
orientation and structural properties of its ®bres may contra-
dict the concept of unilaterality, and furthermore, the
peripheral cross-talk of EMG signals can not be excluded
even if the TMS is unilateral. However, previous studies
have clearly demonstrated that for the CP sphincter muscle
there is very little muscular or neural overlap of innervation
of myo®bres across the midline (Brownlow et al., 1989;
Kristmundsdottir et al., 1990; Medda et al., 1997; Bonning-
ton et al., 1988). Therefore, it is more plausible to suggest
that the notion of bilaterality arises from the motor cortex
itself rather than being the consequence of a peripheral
Magnetic stimulation of the parieto-occipital skull or
occiput, particularly the region ipsilateral to the CP needle
recording site produced very stable and reliable CP-MEPs
Fig. 5. CP muscle recordings obtained from a patient with pseudobulbar
palsy. The cortical CP-MEP was absent (A) while the peripheral CP-MEP with shorter latencies and higher amplitudes than those of
could easily be elicited by stimulation of the parieto-occipital skull region cortical stimulation. Since the swallowing action did not
(B). in¯uence the size and latency of this stable CP-MEP, it is
C. Ertekin et al. / Clinical Neurophysiology 112 (2001) 86±94 93

most probable that these responses were evoked as a conse- P , 0:007). Similar cortical latency values to the vocalis
quence of stimulation of proximal motor ®bres of the vagus muscle of larynx (mean latency of 10.8 ms) have also
nerve either intra- or extra-cranially, as in the case of other been reported (Thumfart et al., 1992). Such latency differ-
cranial musculatures and their proximal motor nerves ences between the CP sphincter muscle and the lingual and
(Benecke et al., 1988; Benecke and Meyer, 1991). laryngeal muscles may indicate that the CP sphincter
When the subjects performed a voluntarily-initiated swal- muscle is linked with the motor cortex via an oligosynaptic
low the cortical CP-MEPs were unequivocally facilitated. motor route.
Increased activity in central neural pathways associated In patients with CP sphincter abnormality, cortical TMS
with pharyngeal and esophageal swallows should excite failed to elicit a CP MEP while the CP-MEP was completely
the cranial motoneurons for several hundred milliseconds normal in response to proximal stimulation of the vagus
(Hamdy et al., 1997; Aziz et al., 1994, 1995). This increased nerve. Patients with hyperre¯exic CP sphincter have
excitation of the CP sphincter motoneurons should occur common clinical features, such as pseudobulbar palsy and
just after the relaxation and opening of the UES, since the signi®cant dysphagia. The absence of CP-MEP is therefore
rebound EMG burst activity takes place after the CP-EMG associated with the involvement of the corticobulbar
pause period and last about 600±800 ms in a decrescendo descending motor ®bres reaching the CP sphincter moto-
manner (Ertekõn et al., 1995, 1998). In both healthy subjects neurons. The hyperre¯exic and disinhibited nature of CP
and patients, swallowing shortened the latency of the CP- sphincter activity should then be strongly related with the
MEP about 2±3 ms and resulted in a signi®cant increase in loss of excitatory (and inhibitory) corticobulbar ®bres in
the amplitude of response, even from 0.2 to 1.0 mV in some ALS and other disorders with degeneration of corticobulbar
cases. Therefore, it was more appropriate to measure the motor ®bres (Ertekõn et al., 1998, 2000). The high and early
CP-MEP parameters from recordings obtained during swal- incidence of corticobulbar tract involvement have recently
lowing. been reported for ALS when the corticobulbar involvement
Although voluntarily-initiated swallowing produced a was demonstrated by magnetic stimulation of tongue and
facilitation of the CP-MEP responses, TMS never induced facial musculature (Urban et al., 1998).
a complete swallowing movement. Similar observations In conclusion, the CP sphincter muscle of the UES should
were also reported previously for other pharyngeal/oesopha- be controlled by corticobulbar ®bres during voluntarily-
geal muscles (Aziz et al., 1995; Hamdy et al., 1997). induced swallows. Although single cortical TMS did not
Furthermore, in experimental animals, single electrical produce actual swallows, the excitatory and inhibitory corti-
stimulation of the cortex also fails to produce swallowing cobulbar motor ®bres probably have a controlling role on
and the initiation of swallowing at the brain stem swallow- the CP muscle. When this descending control is lost as a
ing centre requires spatial summation of synaptic potentials consequence of involvement of corticobulbar ®bres, the
generated by repetitive cortical stimuli (Jean and Car, hyperre¯exic, incoordinated and disinhibited nature of the
1979). However, in one study Valdez et al. (1993) reported CP sphincter muscle is expressed due to the loss of inhibi-
that in three dogs a magnetically induced single stimulus tory and excitatory descending corticobulbar ®bres. There-
delivered to the cerebral cortex produced a contraction in fore, it is now feasible to document this pathogenesis in
the UES and induced swallowing. From the results of the individual cases by means of CP sphincter EMG of UES
present study, it is apparent that the EMG responses evoked together with examination of the cortically evoked motor
in the CP sphincter muscle in response to single TMS ought responses recorded from the CP sphincter muscle.
be the result of direct excitation of the CP sphincter moto-
neurons situated in the nucleus ambiguous. However, as this
direct action fails to produce a swallow, it must either be by- Acknowledgements
passing the neural structures of the central pattern generator
of the brainstem swallowing centre or the descending inputs This study was supported by a grant from the Turkish
from the cortex are not strong enough for the central pattern È BITAK)
Scienti®c and Technological Research Council (TU
generator to induce a swallow. (Project no. SBAG-1739).
In our sample, the mean latency of cortical CP-MEPs was
10.7 ms, varying between 8.0 and 14.0 ms. These latency
values are comparable to the results obtained from the oeso- References
phageal striated muscles, but slightly longer than the phar-
yngeal musculature as reported by Hamdy et al. (1996). Aziz Q, Rothwell JC, Hobson A, Alani S, Bancewicz J, Thompson DG.
They are also longer than the latencies obtained from lingual Esophageal myoelectric responses to magnetic stimulation of the
muscles (Meyer et al., 1997; Ghezzi and Baldini, 1998). human cortex and the extra-cranial vagus nerve. Am J Physiol
Comparison of MEPs of the CP muscle and the cricothyroid 1994;267:G827±G835.
Aziz Q, Rothwell JC, Barlow J, Thompson DG. Modulation of oesophageal
muscle of larynx (CT-MEPs) in 6 of our subjects revealed responses to magnetoelectric stimulation of human brain by swallowing
signi®cantly longer latencies for the CP-MEP (mean latency and by vagal stimulation. Gastroenterology 1995;109:1437±1445.
of 11.2 ms for CP-MEP versus 8.4 ms for CT-MEP; Aziz Q, Rothwell JC, Hamdy S, Barlow J, Thompson DG. The topographic
94 C. Ertekin et al. / Clinical Neurophysiology 112 (2001) 86±94

representation of esophageal motor function on the human cerebral phometric and histopathologic study of the human cricopharyngeus
cortex. Gastroenterology 1996;111:855±862. muscle: in health and the motor neuron disease. Neuropathol Appl
Benecke R, Meyer BU. Magnetic stimulation of corticonuclear systems and Neurobiol 1990;16:461±475.
of cranial nerves in man: physiological basis and clinical application. Medda BK, Lang IM, Dodds WJ, Christl M, Kern M, Hogan WJ, Shaker R.
Electroenceph clin Neurophysiol Suppl 1991;43:333±343. Correlation of electrical and contractile activities of the cricopharyn-
Benecke R, Meyer BU, Schonle P, Conrad B. Transcranial magnetic stimu- geus muscle in the cat. Am J Physiol (Gastrointest Liver Physiol 36)
lation of the human brain: responses in muscles supplied by cervical 1997;273:G470±G479.
nerves. Exp Brain Res 1988;71:623±632. Meyer BU, Werhahn K, Rothwell JC, Roericht S, Faulth C. Functional
Berardelli A, Priori A, Inghilleri M, Cruccu G, Mercuri B, Manfredi M. organisation of corticonuclear pathways to motoneurons of lower facial
Corticobulbar and corticospinal projections to neck muscle motorneur- muscles in man. Exp Brain Res 1994;101:465±472.
ons in man: a functional study with magnetic and electric transcranial Meyer BU, Liebsch R, RoÈricht S. Tongue motor responses following tran-
brain stimulation. Exp Brain Res 1991;87:402±406. scranial magnetic stimulation of the motor cortex and proximal hypo-
Bonnington A, Mahon M, Whitemore I. A histological and histochemical glossal nerve in man. Electroenceph clin Neurophysiol 1997;105:15±
study of the cricopharyngeus muscle in man. J Anat 1988;156:27±37. 23.
Brownlow H, Whitemore I, Willian P. A quantitative study of the histo- Muellbacher W, Mathis J, Hess CW. Electrophysiological assessment of
chemical and morphometric characteristics of the human cricopharyn- central and peripheral motor routes to the lingual muscles. J Neurol
geus muscle. J Anat 1989;166:67±75. Neurosurg Psychiatry 1994;57:309±315.
Campos A, Barona R, Escudero J, Montlt J, Escudero K. Hypoglossal nerve Odergren T, RimpilaÈinen I. Activation and suppression of the sternoclei-
conduction study by transcranial magnetic stimulation in normal domastoid muscle induced by transcranial magnetic stimulation. Elec-
subjects. Otolaryngol Head Neck Surg 1995;112:520±525. troenceph clin Neurophysiol 1996;101:175±180.
Cocito C, Cessono D, Mattei M. Motor evoked potentials in orbicularis oris Odergren T, Rimpilainen I, Borg J. Sternocleidomastoid muscle responses
muscle: no evidence of ipsilateral corticonuclear projections. Muscle to transcranial magnetic stimulation in patients with cervical dystonia.
Nerve 1993;16:1268±1269. Electroenceph clin Neurophysiol 1997;105:44±52.
Cruccu G, Berardelli A, Inghilleri M, Manfredi M. Functional organisation Pavesi G, Macaluso GM, Tinchelli S, Medici D, Gemignami F, Mancia D.
of the trigeminal system in man. Brain 1989;112:1333±1350. Magnetic motor evoked potentials (MEPs) in masseter muscles. Elec-
Cruccu G, Berardelli A, Inghilleri M, Manfredi M. Corticobulbar projec- troenceph clin Neurophysiol 1991;31:303±309.
tions to upper and lower facial motor neurons: a study by magnetic Rossini PM, Barker AT, Berardelli A, Caramia MD, Caruso G, Cracco RQ,
transcranial stimulation in man. Neurosci Lett 1990;117:68±73. Dimitrijevic MR, Hallett M, Katayama Y, Lucking CH, Maertens de
Ertekõn C. Clinical diagnosis and electrodiagnosis of swallowing disorders. Noordhout AL, Marsden CD, Murray NMF, Rothwell JC, Swash M,
In: Swenson MR, editor. Disorders of speech and swallowing, AAEM Tomborg C. Non-invasive electrical and magnetic stimulation of the
19th Annual Continuing Education courses, Minneapolis, MN: John- brain, spinal cord and roots: basic principles and procedures for routine
son, 1996. pp. 23±33. clinical application. Report of an IFCN committee. Electroenceph clin
Ertekõn C, Hansen MV, Larsson LE, SjoÈdahl R. Examination of the Neurophysiol 1994;91:79±82.
descending pathways to the external anal sphincter and pelvic ¯oor RoÈssler KM, Hess CW, Schmid VD. Investigation of facial motor pathways
muscles by transcranial cortical stimulation. Electroenceph clin Neuro- by electrical and magnetic stimulation: sites and mechanisms of excita-
physiol 1990;75:500±510. tion. J Neurol Neurosurg Psychiatry 1989;52:1149±1156.
Ertekõn C, Pehlivan M, Aydogdu I, Ertas M, Uludag B, Celebi G, Colakoglu Schaefer SD. Laryngeal electromyography. Otolaryng Clin North Am
Z, Sagduyu A, YuÈceyar N. An electrophysiological investigation of 1991;24:1053±1057.
deglutition in man. Muscle Nerve 1995;18:1177±1186. Schriefer TN, Mills KR, Murray NMF, Hess CW. Evaluation of proximal
Ertekõn C, Aydogdu I, YuÈceyar N, Tarlaci S, Kiylioglu N, Pehlivan M, facial nerve conduction by transcranial magnetic stimulation. J Neurol
Celebi G. Electrodiagnostic methods for neurogenic dysphagia. Elec- Neurosurg Psychiatry 1988;51:60±66.
troenceph clin Neurophysiol 1998;109:331±340. Thumfart WF, Pototschnig C, Zorowka P, Eckel HE. Electrophysiologic
Ertekõn C, Aydogdu I, YuÈceyar N, Kiylioglu N, Tarlaci S, Uludag B. investigation of lower cranial nerve disease by means of magnetically
Pathophysiological mechanisms of oropharyngeal dysphagia in amyo- stimulated neuromyography of the larynx. Ann Otol Rhinol Laryngol
trophic lateral sclerosis. Brain 2000;123:125±140. 1992;101:629±634.
Ghezzi A, Baldini S. A simple method for recording motor evoked poten- Turnbull GK, Aziz Q, Hamdy S, Barlow J, Singh K, Alani S, Thompson
tials of lingual muscles to transcranial magnetic and peripheral electri- DG. Representation of the anal sphincter on the human cerebral cortex
cal stimulation. Electroenceph clin Neurophysiol 1998;109:114±118. (abstract). Gut 1994;35:S30.
Ghezzi A, Callea L, Zaffaroni M, Zibetti A. Motor potentials of inferior Urban PP, Hopf HC, Connennann HP, Hundemer HP, Koehler J. The
orbicularis oculi muscle to transcranial magnetic stimulation: compar- course of cortico-hypoglossal projections in human brainstem: func-
ison with responses to electrical peripheral stimulation of facial nerve. tional testing using transcranial magnetic stimulation. Brain
Electroenceph clin Neurophysiol 1992;85:248±252. 1996;119:1031±1038.
Hamdy S, Aziz Q, Rothwell JC, Singh KD, Barlow J, Hughes DG, Tallis Urban PP, Beer S, Hopf HC. Cortico-bulbar ®bers to orofacial muscles:
RC, Thompson DG. The cortical topography of human swallowing recordings with enoral surface electrodes. Electroenceph clin Neuro-
musculature in health and disease. Nature Med 1996;2(11):1217±1224. physiol 1997;105:8±14.
Hamdy S, Aziz Q, Rothwell JC, Hobson A, Barlow J, Thompson DG. Urban PP, Vogt T, Hopf HC. Corticobulbar tract involvement in amyo-
Cranial nerve modulation of human cortical swallowing motor path- trophic lateral sclerosis: a transcranial magnetic stimulation. Brain
ways. Am J Physiol 1997;272:G802±G808. 1998;121:1099±1108.
Herdmann J, Bielefeldt K, Enck P. Quanti®cation of motor pathways on the Valdez DT, Selapatek A, Niznik G, Linden RD, Diamant NE. Swallowing
pelvic ¯oor in humans. Am J Physiol 1991;260:G720±G723. and upper esophageal sphincter contraction with transcranial magnetic-
Jean A, Car A. Inputs to the swallowing medullary neurons from the periph- induced electric stimulation. Am J Physiol (Gastrointest Liver Physiol
eral afferent ®bers and the swallowing cortical area. Brain Res 27) 1993;264:G213±G219.
1979;178:567±572. Yin SS, Qiv WW, Stucker FJ. Major patterns of laryngeal electromyogra-
Kristmundsdottir F, Mahon M, Froed MMQ, Cumming WJK. Histomor- phy and their clinical application. Laryngoscope 1997;107:126±136.