J Appl Physiol 116: 291–301, 2014.
First published October 3, 2013; doi:10.1152/japplphysiol.00670.2013.
Review
Upper Airway Control and Function: Implications
for Sleep-Disordered Breathing
HIGHLIGHTED TOPIC
Activation of upper airway muscles during breathing and swallowing
Ralph F. Fregosi1,2 and Christy L. Ludlow3
1
Department of Physiology, University of Arizona, Tucson, Arizona; 2Department of Neuroscience, University of Arizona, Tucson,
Arizona; and 3Department of Communication Sciences and Disorders, James Madison University, Harrisonburg, Virginia
Submitted 11 June 2013; accepted in final form 29 September 2013
control of breathing; larynx; pharynx; respiratory muscles; swallowing
CONTROLLING UPPER AIRWAY MUSCLES is one of the most daunting
problems that the mammalian central nervous system must
solve. Patterns of muscle control must rapidly alternate between different system requirements for respiration, speech,
swallowing, and upper airway protection. Breathing and swallowing, the subject of this brief review, are highly automated
behaviors driven by central pattern generators. We review the
functional anatomy and neural innervation of tongue and laryngeal muscles, and how the muscle activities are altered as
respiratory drive changes and when swallowing is required.
We also consider how muscle activity is altered by central
nervous system state, chemoreceptor stimulation, changes in
lung volume, and during swallowing. We also try to identify
important gaps in our knowledge and address the hurdles that
limit our understanding of these motor systems. Because this is
a brief review, we had to be selective in the topics covered and
in the use of citations. As a result, we regret that many
outstanding studies of upper airway muscle function during
breathing and swallowing could not be reviewed and that
consideration of the crucial role played by muscles of the
pharyngeal wall also had to be passed over.
MAMMALIAN TONGUE MUSCLES: FUNCTIONAL ANATOMY
AND INNERVATION
The anatomy of mammalian tongue muscles has been reviewed extensively (13, 14, 83, 123, 147) and will be summaAddress for reprint requests and other correspondence: R.F. Fregosi, Dept.
of Physiology, Univ. of Arizona, Tucson, AZ 85721-0093 (e-mail: fregosi
@u.arizona.edu).
http://www.jappl.org
rized briefly here. Four of the tongue muscles are extrinsic
muscles, which originate on bony structures or connective
tissue and insert into the tongue body (the genioglossus,
hyoglossus, styloglossus, and palatoglossus),1 and four are
intrinsic muscles (inferior longitudinalis, superior longitudinalis, transversus, and verticalis) in which the fibers are wholly
contained within the tongue body, or blade (reviewed in 37,
38), though there is evidence that some intrinsic fibers attach to
the hyoid bone (44, 46). The tongue and other upper airway
muscles are small compared with other respiratory muscles,
their fibers intermingle extensively within the tongue body, and
their innervation is complex (Fig. 1, A and B) (see 37, 91, 92,
97, 98, 137, 140). Collectively, these unique muscles produce
a variety of intricate but well-controlled movements, including
retraction, protrusion, elevation, and depression of the tongue,
as well as alterations in tongue shape and stiffness. Because the
tongue is unattached on one end, it can move with almost
infinite degrees of freedom, and force production by one
muscle depends on the cocontraction of some or all of the other
muscles.
The tongue muscles are typically divided functionally into
protrudors or retractors, reflecting their principal actions. Retractor muscles pull the tongue backward, toward the posterior
pharyngeal wall, and include the extrinsic hyoglossus and
1
Because the palatoglossus originates on the palatine aponeurosis and
inserts into the posterolateral tongue, it is sometimes considered a palatal
muscle and sometimes a tongue muscle. The motor innervation of palatoglossus is via the pharyngeal plexus, not the hypoglossal nerve. Thus, the tongue
is often considered to have three extrinsic muscles.
8750-7587/14 Copyright © 2014 the American Physiological Society
291
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Fregosi RF, Ludlow CL. Activation of upper airway muscles during breathing
and swallowing. J Appl Physiol 116: 291–301, 2014. First published October 3,
2013; doi:10.1152/japplphysiol.00670.2013.—The upper airway is a complex muscular tube that is used by the respiratory and digestive systems. The upper airway
is invested with several small and anatomically peculiar muscles. The muscle fiber
orientations and their nervous innervation are both extremely complex, and how the
activity of the muscles is initiated and adjusted during complex behaviors is poorly
understood. The bulk of the evidence suggests that the entire assembly of tongue
and laryngeal muscles operate together but differently during breathing and swallowing, like a ballet rather than a solo performance. Here we review the functional
anatomy of the tongue and laryngeal muscles, and their neural innervation. We also
consider how muscular activity is altered as respiratory drive changes, and briefly
address upper airway muscle control during swallowing.
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Upper Airway Function in Breathing and Swallowing
B
C
D
Fregosi RF et al.
Rest position
Anterior protrusion
Fig. 1. Anatomy of the human tongue musculature. A highlights the extrinsic musculature, with the arrows showing the approximate movement of the tongue
when one of the muscles is stimulated in isolation. [Borrowed with permission from (38).] B shows extrinsic and intrinsic fibers of the human tongue using in
vivo imaging with tractography. Sl, superior longitudinalis; il, inferior longitudinalis; pg, palatoglossus; v, verticalis; sg, styloglossus; gg, genioglossus; hg,
hyoglossus; gh, geniohyoid. The intermingling of extrinsic and intrinsic fibers is obvious. Note that the transversus muscle is not easily seen in sagittal section,
as is the case here. [Borrowed with permission from (44).] C: transverse section through the human tongue blade to show the transversus muscle fibers, which
are labeled with an A. D is a simplified model of a muscular hydrostat. Activation of transversus and verticalis fibers (and likely vertically oriented fibers of the
genioglossus and hyoglossus) reduces the lateral diameter of the box (i.e., the tongue) while increasing the length of its anterior-posterior axis, resulting in
elongation with no change in volume. This change in shape, together with forward movement of the tongue base (driven largely by the genioglossus muscle)
results in protrusion and anterior displacement of the tongue tip (see text).
styloglossus, and the intrinsic inferior and superior longitudinalis muscles. Protrudor muscles move the tongue blade and
base forward, and include the extrinsic genioglossus, and the
intrinsic verticalis and transversus muscles. Although classifying the muscles in this way is convenient, precisely how the
tongue moves when the muscles are stimulated in isolation is
poorly understood. With care, selective stimulation of protrudor and retractor muscle groups, as well as some of the
intrinsic muscles, can be done in rats (8, 40, 47) and human
subjects (104, 129), but movements other than simple protrusion or retraction are difficult to quantify. It does appear that
both the genioglossus and hyoglossus also cause depression of
the tongue base, sharing this common action. This may explain
why coactivating protrudor and retractor muscles both dilates
and stiffens the pharyngeal airway in both rodent (41) and
human (32, 104) models (see below). The styloglossus causes
elevation of the sides of the tongue blade, as well as retraction.
The intrinsic muscles are most often associated with changes
in tongue shape (139), though they clearly assist in protrusion
and retraction (see below). Most of what we know of intrinsic
muscle actions has been inferred from the elegant modeling
work of Kier and colleagues (65, 101, 65a), where they
developed the notion of the tongue as a muscular hydrostat. A
muscular hydrostat can move by displacing its tissues, while
also providing the structural support that the movement requires. Hydrostats take advantage of their high water content,
and thus incompressible nature, to elongate, shorten and stiffen
without changing volume. In a constant volume structure,
opposing changes along the anterior-posterior axis must be
offset by changes along the lateral axis (Fig. 1C). As such,
longitudinalis muscle contraction is purported to increase the
lateral axis (making the tongue thicker in the transverse plane)
while shortening the anterior-posterior axis and causing an
effective retraction. The verticalis and transversus muscles are
thought to shorten the lateral axis of the tongue, thereby increasing
the anterior-posterior axis and causing an effective protrusion. As
pointed out by Gaige and colleagues (44, 46), muscular hydrostats
require fibers that are arranged in multiple orientations around the
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A
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Upper Airway Function in Breathing and Swallowing
Fig. 2. Schematic diagram showing the results of simulated tongue protrusion.
A depicts forward displacement of the tongue tip and base from the resting
position (dashed line). The fibers of different muscles are color coded and
correspond to the nomenclature in B. B shows the percentage activation of each
of the participating tongue muscles during the simulated protrusion. Note that
three of the intrinsic muscles assist the posterior and medial fibers of the
genioglossus. TRANS, transversus; GGP, genioglossus posterior; GGM, genioglossus medial; VERT, verticalis; SL, superior longitudinalis; ML, mylohyoid. [Borrowed with permission from (144).]
Fregosi RF et al.
293
there are likely important species differences (31, 47, 48, 70,
91, 92, 140, 148). Careful muscular isolation and tracer injection studies by McClung and Goldberg in adult rats (90, 91)
show that the ventral subdivision of the nucleus contains a
greater proportion of protrudor muscle motoneurons, while the
dorsal subdivision contains more retractor motoneurons. Their
data also show that intrinsic and extrinsic muscle motoneurons
overlap extensively, and extend from about 0.9 mm below the
obex to about 0.9 mm above, with the extrinsic column a few
hundred microns longer than the intrinsic column (91). There
are also interesting data showing that there may be some
musculotopic organization within a tongue muscle. For example, the horizontal fibers of the genioglossus muscle, which
pull the base of the tongue forward, and the vertical fibers
which likely participate in tongue shaping, are innervated by
spatially distinct populations of motoneurons (92). Since the
dendrites of hypoglossal motoneurons branch extensively and
extend for at least 500 ␮m even in juvenile rats (102), it is easy
to envision synaptic coupling between motoneurons that are
separated by long distances; thus the functional significance of
musculotopic organization of the hypoglossal motoneuron pool
is unknown.
When the complexity of the muscular and nervous anatomy
of the tongue is considered, it is clear why accessibility to
either nerves or muscles has dictated the nature of physiologic
studies on the tongue motor system and therefore what we
know about it. For example, the great majority of all experiments of respiration-related control of the tongue muscles have
used the genioglossus muscle or the main trunk of the hypoglossal nerve as the index of respiration-related motor drive to
the tongue musculature. As a result, we have learned a lot
about the function of the genioglossus muscle or how all
hypoglossal motoneurons behave in concert, but our understanding of tongue function in breathing and swallowing is
incomplete, simply because the actions of the majority of its
muscles have not been studied. Future work should be focused
on enhancing our understanding of the function of all tongue
muscles, including how the different muscles interact to produce the complex movements observed in breathing, swallowing, mastication, and speech. Similarly, studies of whole hypoglossal nerve activity or hypoglossal motoneurons without
identifying their muscular targets provides no information
about the activation of a specific muscle (see 37).
Finally, although the general features of tongue muscle
anatomy, innervation, and function are similar in commonly
used experimental mammals, such as rats, cats, and mice, the
human tongue musculature and its innervation do differ in
some respects. For example, the human tongue musculature
tends to have a relatively dense neural innervation, variable
patterns of motor end-plate morphology and density, and in
some muscles, including the genioglossus, examples of neuromuscular compartmentalization. However, the majority of the
specializations in human tongue muscle innervation are found
in the intrinsic muscles (97). The authors of this work (97)
suggest that these observations are consistent with improved
control of tongue shape in humans compared with lower
mammals, likely in support of speech, as has long been
recognized (145). In the context of the present review, these
specializations may lead to species differences in the regulation
of pharyngeal airway size and/or stiffness by tongue muscle
contraction. A variety of studies suggest that qualitative dif-
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long axis. Moreover, the different fibers interdigitate extensively
in the tongue body so activating motor units across the muscle
fiber populations allows an enormous number of potential movements, and may afford the system with the ability to accomplish
a given task with different sets of muscles and muscle fibers. Such
redundancy could be important in conditions such as stroke or
following carotid endarterectomy, wherein 5% or more of patients
suffer hypoglossal nerve injury, but the ability to protect the
airway, to chew, to swallow, and to speak are only mildly affected
or can be relearned (12, 49). A major tenet of the muscular
hydrostat hypothesis that is often overlooked is that the model
requires that multiple muscles participate in all tongue movements. This thesis is confirmed in modeling studies, wherein
anterior displacement of the tongue requires the bilateral activation of the genioglossus muscle but also activation of the intrinsic
transversus, verticalis, and superior longitudinal muscles (144)
(Fig. 2).
Branches of the hypoglossal nerve supply all of the tongue
muscle fibers. The main nerve trunk bifurcates into large
medial and lateral branches as it approaches the muscles, with
the medial branch containing axons supplying the protrudor
muscles (both intrinsic and extrinsic muscles) and the lateral
branch the retractors. The intrinsic muscle branches tend to be
distal and are very small and numerous, making selective
denervation or stimulation extremely difficult. There have been
several studies of the musculotopic organization of the hypoglossal motor nucleus, and some general rules emerge though
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Upper Airway Function in Breathing and Swallowing
ferences, however, are few, despite notable differences in
pharyngeal airway size and shape (and the distance between
the epiglottis and the tip of the soft palate) between humans
and lower mammals. For example, chemoreceptor stimulation
coactivates tongue protrudor and retractor muscles in humans
(88) and rats (40); the control of pharyngeal constrictor muscles during chemoreceptor stimulation is similar in cats and
human subjects (74); and coactivation of protrudor and retractor muscles similarly stiffens and dilates the pharynx in humans (32, 104) and rats (41). Thus the tongue musculature, its
general neural innervation patterns (97), and, importantly, its
mechanical actions are remarkably well conserved. Accordingly, in the following sections species differences will be
addressed only when relevant.
MAMMALIAN TONGUE MUSCLES: RESPONSE TO CHANGES
IN RESPIRATORY DRIVE
Fregosi RF et al.
both populations increasing their activity in hypercapnia (5)
and hypoxia (9). Taken together, these results are consistent
with excitation of a large fraction of the hypoglossal motor
neuron pool with stimulation of central and/or peripheral
chemoreceptors.
Tracheal occlusion in animal models or breath holding in
human subjects also coactivates genioglossus and hyoglossus
muscles, hyoglossus (88), and the activity recorded from the
medial and lateral hypoglossal nerve branches in rodents (40,
81), consistent with strong, broadly distributed inhibition of
hypoglossal motoneurons by pulmonary stretch receptor afferents (10, 55, 72). Similarly, experimentally removing lung
volume feedback with brief (1–2 respiratory cycles) airway
occlusions in animal models increases both genioglossus, hyoglossus, and intrinsic tongue muscle activities (5, 6, 9, 10),
showing that lung inflation mediated inhibition of hypoglossal
motoneurons is distributed broadly to motoneurons innervating
multiple tongue muscles. Both genioglossus and hyoglossus
activities are also markedly inhibited following spontaneously
augmented breaths (59), indicating that the results of studies
using airway occlusions do not reflect experimental artifact. In
addition to inputs from the pulmonary airways and central and
peripheral chemoreceptors, hypoglossal motoneurons also receive afferent inputs from mechanoreceptors in the upper
airway mucosa, both in animal models and in human subjects
(25, 52, 87, 89, 118, 133). Recent studies show that negative
pressure pulses applied to the pharynx results in coactivation of
the genioglossus and hyoglossus muscles in anesthetized rats
(119), again suggesting that afferent inputs to hypoglossal
motoneurons are distributed throughout the motoneuron pool.
Although the bulk of the work on central nervous system
state changes and neural drive to tongue muscles has focused
on differences between wakefulness and sleep, exercise affords
an opportunity to examine the influence of a heightened central
nervous system state on neural drive to the tongue muscles.
Studies in exercising rodents are equivocal, with one study
showing that treadmill exercise training (5 days/wk for 8 wk)
altered the balance of myosin heavy chain subtypes in the
genioglossus muscle (67), consistent with muscle activation
during the exercise training sessions. However, another group
did not find changes in myosin heavy chain phenotype or
oxidative capacity in the genioglossus following treadmill
exercise performed 4 times per week for 12 wk (151). Although these observations in rodents suggest that the tongue
muscles may not be vigorously activated during exercise, we
are unaware of any measures of rodent tongue muscle activities
(e.g., EMG) during exercise. In other words, the extent of
upper airway muscle activation in rodents may be insufficient
to induce cellular changes in the muscle fibers. In exercising
horses, bilateral hypoglossal nerve block induced nasopharyngeal narrowing, suggesting that the tongue muscles play an
important role in equine airway defense during exercise (27).
Studies in human subjects show that bicycle exercise increases
the genioglossus muscle EMG activity in an intensity-dependent manner (134, 156), with the EMG reaching 40% of its
maximal value at peak exercise intensities (156). Interestingly,
the drive to the genioglossus was shown to be the same
whether the subjects exercised while upright or supine (156),
but the activity did increase briskly as soon as subjects
switched from nasal to oronasal breathing. The latter observation suggests that drive to the genioglossus muscle depends
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The hypoglossal motor nucleus receives both excitatory and
inhibitory synaptic input from many brain regions. Direct
inputs originate in the nucleus of the solitary tract, the majority
of the reticular nuclei, the principal and spinal trigeminal
nuclei, reticularis subcoeruleus, the caudal Raphe nucleus, and
the Kolliker-Fuse nucleus (149). These regions, in turn, receive
higher order inputs from the frontal, insular and parietal cortices, several cerebellar nuclei, the substantia nigra, the superior colliculus, and the mesencephalic trigeminal nucleus
(149). Many of these regions modulate ventilatory drive, with
the reticular formation containing the interneurons that link the
central respiratory drive from the pre-Bötzinger complex with
the hypoglossal motor nucleus (68, 69). The activity in most of
these brain regions is highly dependent on central nervous
system state, with the wakefulness drive reduced in sleep, and
increased in exercise.
The role of central nervous system state in controlling drive
to hypoglossal motoneurons, and thus tongue muscles, has
attracted considerable interest since reductions in genioglossus
muscle electromyographic (EMG) activity during sleep was
first described (116, 128). This topic has been reviewed extensively in recent years (29, 43, 51, 71, 85), and there is an
emerging consensus that non-rapid eye movement sleep is
associated with reductions in excitatory neuromodulatory inputs primarily from noradrenergic (1, 36), serotonergic (19, 36,
80, 141), and cholinergic neurons (16, 24, 82), while during
REM sleep there is also direct synaptic inhibition of hypoglossal motoneurons (33, 42). These observations have, in turn, led
to several studies of the influence of hypercapnia, hypoxia, and
lung volume–related reflexes on the drive to hypoglossal motoneurons and tongue muscles.
Whole hypoglossal nerve activity, which provides an index
of the summed activity of all motor axons in electrical contact
with the recording electrode, increases with hypercapnia and
hypoxia in animal models (15, 21, 56, 73, 96, 142, 154). EMG
recordings also consistently show that hypercapnia and hypoxia increase drive to the genioglossus muscle in various
species (5, 9, 40, 53, 94, 130, 150), including humans (62, 66,
88, 103, 105, 107–109, 143). More recent studies have shown
that drive to both the hyoglossus and genioglossus muscles
increases in parallel with hypercapnia or hypoxia in animal
models (9, 10, 40, 58) and in humans (88). Similarly, intrinsic
tongue muscles are also coactive with extrinsic muscles, with
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Fregosi RF et al.
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drop in the minimum firing rate (expiration), rather than an
increase in peak firing rate (inspiration). Thus during exercise
in healthy human subjects the increase in inspiratory-related
drive to the genioglossus muscle is the result of recruitment of
previously silent motor units and a shift in the firing behavior
of already active units to inspiratory-phase-dependent bursting
(153). In summary, increased respiration-related neural drive to
the tongue muscles is mediated largely, though not entirely, by
motor unit recruitment. This is likely a task-dependent feature
of the system, as animal studies clearly show that individual
motoneurons are capable of increasing their firing rate. Moreover, volitional increases in drive to the human genioglossus
muscle are associated with marked increases in firing rate (11,
114). These observations coupled with the findings showing
that multiple tongue muscles are coactivated in phase with
inspiration, as discussed above, suggest that drive to the hypoglossal motor nucleus is distributed widely, both within and
across muscle motoneuron pools.
MAMMALIAN TONGUE MUSCLES: ROLE IN SWALLOWING
In contrast with respiration requiring dilation of the oropharynx, swallowing requires compression of the oropharynx to
propel the bolus (liquid or food) through the hypopharynx and
into the upper esophageal sphincter. In the human, forceful
retraction of the tongue base coordinated with three dimensional pharyngeal compression moves the bolus into and
through the upper esophageal sphincter (99). Due to the angle
of the oropharynx in the human, anterior and superior motion
of the hyoid and larynx pull the laryngeal vestibule up behind
the epiglottis to reduce airway entry. These actions may depend upon the geniohyoid and mylohyoid, respectively (113).
Bolus propulsion to move the bolus through the hypopharynx
depends upon a complex cocontraction of intrinsic and extrinsic tongue muscles: the hyoglossus, geniohyoid, styloglossus,
and intrinsic tongue muscles (35).
MAMMALIAN LARYNGEAL MUSCLES: FUNCTIONAL
ANATOMY AND INNERVATION
The laryngeal muscles must control the vocal folds for
multiple functions, opening for inspiration, closing for airway
protection during swallow, and rapid opening and closing to
build up pressure for airway clearance during cough. For
vocalization the two folds must be held in the midline to allow
for vibration on expiratory airflow. Speech and singing require
rapid opening and closing of the vocal folds with precise
regulation of length and tension to control the frequency of
vibration and vocal intensity in coordination with expiratory
airflow. The motoneurons for the laryngeal muscles are arranged in the nucleus ambiguus, from the rostral end for the
cricothyroid muscle to the posterior cricoarytenoid, lateral
cricoarytenoid, and thyroarytenoid in the more caudal region
(28). The laryngeal muscles are controlled by brain stem
systems for respiration and swallowing (30). For respiration,
both the pre-Bötzinger complex for inspiratory pacing and the
retrotrapezoid nucleus-parafacial respiratory group in the medulla have inputs to the laryngeal motoneurons for inspiratory
and expiratory output, respectively (34). For swallowing, neurons in the ventral swallowing group have inputs to the laryngeal motoneurons (60). During respiration, the vocal folds are
actively opened to reduce airflow resistance during inspiration
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importantly on changes in jaw position (84) and/or activation
of pressure-sensitive mechanoreceptors in the mouth and pharynx.
Studies of the respiration-related activities of single hypoglossal motoneurons or genioglossus muscle motor units have
been reviewed recently (4, 45). The discharge pattern in animal
models tends to be very strongly inspiratory modulated (19, 54,
55, 61, 95, 135), though limited numbers of neurons with other
discharge patterns have been observed in cats (54, 55, 95, 135).
In contrast, recordings of motor unit discharge in human
subjects do show phasic inspiratory discharge, but many of
these units show mainly tonic discharge, with an increase in
their firing rate during the inspiratory phase (4, 7, 117).
Saboisky et al. (120) have described units with apparently rigid
discharge patterns that confine them to fire in expiration, in
inspiration or tonically. On the basis of these observations, they
suggested that there must be unique premotor inputs that also
have one of these three stereotyped discharge patterns and
convey this information, apparently unaltered, to hypoglossal
motoneurons. Of course, an alternate interpretation is that
factors such as posture, central nervous system state, and upper
airway mechanics dictate whether excitatory synaptic input,
and thus motoneuron activation, is phasic or tonic (4), providing units with the flexibility to switch their discharge pattern.
Support for this latter point is nicely illustrated in exercising
human subjects (152).
Increasing respiratory drive with hypercapnia or hypoxia
tends to increase hypoglossal motoneuron discharge frequency,
with changes in firing rate more consistent in cells where
discharge is confined to the inspiratory phase (54, 55, 61, 95).
Both hypoxia and hypercapnia also recruit motoneurons that
were inactive under baseline conditions (54, 55, 61, 95).
Although it is difficult to quantify the relative contributions of
rate coding and recruitment to the overall neural drive to a
muscle, estimates suggest that recruitment of motor units
accounts for about 75% of the total increase in genioglossus
muscle EMG between baseline and maximal hypercapnic stimulation (61). Hypoglossal motoneurons strongly increase their
firing rate when lung inflation is withheld for a single respiratory cycle (55, 135). The latter observation suggests that
suppression of motoneuron firing rate underlies the inhibition
of hypoglossal motoneuron population output or drive to individual tongue muscles by lung inflation discussed above,
though the extent to which lung inflation suppresses motoneuron recruitment is unknown.
Studies in human subjects, all based on the recording of
motor units from the genioglossus muscle, generally confirm
the findings in animal models in that recruitment seems to
dominate the increase in drive to the muscle evoked by chemoreceptor stimulation (100, 117, 121). Similarly, the increase in
drive to the genioglossus muscle with arousal is dominated by
the recruitment of units that were inactive during sleep, while
the decrease in drive with the transition from wakefulness to
sleep (7, 155) is dominated by a drop out of motor units with
either very little or no change in discharge rate. Consistent with
these observations, recent studies of genioglossus motor unit
activity during exercise show that the increase in the magnitude
of multiunit EMG activity is due largely to motor unit recruitment as exercise intensity increases. Although there was evidence of within-breath firing rate modulation that averaged
about 8 Hz, the modulation in this study was the result of a
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Fig. 3. A shows the cricoarytenoid joint facet on the rim of the cricoid cartilage
on the left (CA) and the arytenoid cartilage on the joint facet on the right (AC)
with the muscular process (MP) in the back, the point of attachment of the
posterior cricoarytenoid and lateral cricoarytenoid muscles and the vocal
process (VP) in the front with the motion of the vocal process for abduction
moving up and outward. [Borrowed with permission from (132).] B shows how
the superior view of the larynx reduces the two-dimensional motion of the
vocal process to a lateral medial motion (132). Ci is reconstructed from MRI
scans of a human larynx with the vectors of the posterior cricoarytenoid (PCA)
and lateral cricoarytenoid (LCA) muscles attached from the muscular process
of the arytenoid to different points on the cricoid cartilage. [Borrowed with
permission from (131).] Cii shows the vectors of the thyroarytenoid (TA)
muscle and the vocalis (VF) attaching the front aspect of the arytenoid
cartilage to the thyroid cartilage (131).
Fregosi RF et al.
The laryngeal muscles can be grouped by function and
innervation. Only one muscle opens or abducts the vocal folds,
the posterior cricoarytenoid muscle. As it shortens with contraction it pulls the muscular process of the arytenoid cartilage
backward on the rim of the cricoid cartilage; this action results
in motion of the vocal process of the arytenoid cartilage lateral
and upward to open the vocal folds (132) (Fig. 3C). The
cricothyroid muscle stretches the vocal fold by pulling the
thyroid cartilage forward and downward over the cricoid cartilage increasing the distance from the anterior insertion of the
vocal fold to its insertion on the voice process of the arytenoid. Some have also suggested that with the action of the
cricothyroid muscle to pull the thyroid cartilage downward
over the cricoid, it widens the vocal fold opening as the thyroid
descends over the cricoid cartilage, further adding to vocal fold
abduction action by the cricothyroid muscle in the human (20).
Three other intrinsic laryngeal muscles are all thought to add to
vocal fold closing but with different actions. The thyroarytenoid muscle comprises the vocal fold attaching the anterior
surface of the arytenoid cartilage to the inner surface of the
thyroid cartilage and contains two compartments, one the
vocalis and another lateral to the vocalis, the thyroarytenoid
(125). As the thyroarytenoid contracts, it shortens the vocal
fold and pulls the vocal process down and inward toward the
midline adding to vocal fold closure (Fig. 3C). The lateral
cricoarytenoid and the interarytenoid muscles also close the
vocal fold. (Fig. 3C).
Innervation of the laryngeal muscles involves two nerves,
the external branch of the superior laryngeal nerve, which
innervates the cricothyroid, and the recurrent laryngeal nerve,
which innervates the other four muscles. The external branch
of the superior laryngeal nerve separates laterally from the
internal branch before the internal branch enters the larynx
through the thyrohyoid membrane to branch under the surface
of the epiglottis, sending separate branches to the mucosa in
the laryngeal vestibule, particularly over the surface covering
the arytenoid cartilages (124). The external branch enters the
cricothyroid muscle, which is thought to involve at least two
separate compartments likely innervated by different branches
of the nerve: the rectus in the anterior portion pulling the
thyroid cartilage downward over the cricoid and the oblique
which is more lateral and pulls the thyroid cartilage forward
relative to the cricoid. An additional lateral compartment has
been proposed in the canine (122). The external branch of the
superior laryngeal nerve innervates the cricothyroid muscle.
Some have proposed that the internal branch of the superior
laryngeal nerve also innervates the interarytenoid muscle in the
human (124), although no physiological evidence of this has
been reported.
The other intrinsic laryngeal muscles are innervated by the
recurrent laryngeal nerve: the posterior cricoarytenoid, the
interarytenoid, the lateral cricoarytenoid, and the thyroarytenoid. The recurrent laryngeal nerve ascends toward the larynx
in the trachea-esophageal groove as the inferior laryngeal nerve
entering the larynx from the posterior aspect. It first sends
fibers to innervate the posterior cricoarytenoid, then the lateral
cricoarytenoid, while the anterior branch travels laterally to
innervate the thyroarytenoid (126).
The activation patterns of the laryngeal muscles vary between respiration, swallowing, cough, and voice. The only
abductor muscle, the posterior cricoarytenoid, is the only
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similar to the dilation that occurs in the oropharynx and
pharyngeal musculature. During expiration, the vocal folds
partially close to provide some resistance during expiratory
flow by active respiratory control of the laryngeal motoneurons
(26, 76). During swallowing, the larynx closes for airway
protection to prevent food or liquid from passing into the
trachea in the middle of swallowing at three levels, the vocal
folds, the ventricular/false folds, and the epiglottis (64). The
laryngeal muscles are also controlled for mammalian vocalization by an innately controlled network in the midbrain and
brainstem (63). In humans, fine control of the laryngeal muscles for speech develops in the cortex, cerebellum, and basal
ganglia (136). For singing, highly skilled control of the laryngeal muscles emerges with training that involves these same
brain regions, as well as auditory integration (106).
The cricoarytenoid joint limits the actions of the laryngeal
muscles. The arytenoid cartilages articulate with the posterior
cricoarytenoid joint facet on the posterior rim of the cricoid
cartilage. The joint facet limits rotation and sliding to a minimum and allows rocking of the arytenoid on the cricoid rim
from down and inward for adduction of the folds, to up and
outward for abduction of the folds (Fig. 3A). Thus the action is
two dimensional, but because most views of the larynx are
superior only, the superior-inferior dimension is erroneously
interpreted as a swinging of the vocal process from lateral for
opening to medial for closing (132) (Fig. 3B).
•
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Upper Airway Function in Breathing and Swallowing
MAMMALIAN LARYNGEAL MUSCLES: RESPONSE TO
CHANGES IN RESPIRATORY DRIVE
During quiet respiration, the posterior cricoarytenoid is active for inspiration to open the vocal folds with phasic firing of
some units prior to the onset of inspiration and tonic firing
throughout the cycle (75). The thyroarytenoid muscle is active
during quiet respiration, with both phasic and tonic firing
patterns being higher during inspiration but also present during
Fregosi RF et al.
297
expiration (26). Increasing inspiratory drive increases posterior
cricoarytenoid activity as it adds to widening of the upper
airway from the nasal alae downward (18, 127, 146). With
hypercapnia, not only does the posterior cricoarytenoid muscle
activity increase to widen vocal fold opening during inspiration
to reduce airway resistance, but also the thyroarytenoid muscle
increases in level of activation during expiration to reduce
airflow and maintain alveolar expansion (2, 57, 76, 79). Thus
both the vocal fold abductor and adductor muscles are active in
relation to respiratory drive with tonic and phasic motor unit
firing patterns associated with vocal fold valving during inspiration and expiration for both involuntary and voluntary
changes in breathing (75, 78). Further, voluntary sniff maximally opens the vocal folds with rapid phasic recruitment of
both the posterior cricoarytenoid and the cricothyroid muscles
in humans which is used clinically to test for abductor muscle
function (115).
INFLUENCE OF SWALLOWING ON THE LARYNGEAL AND
TONGUE MUSCLES
Swallowing requires rapid and complete closure of the entry
to the laryngeal vestibule while allowing the opening of the
upper esophageal sphincter for the liquid or food to enter the
esophagus and clear the hypopharynx. Extrinsic laryngeal
muscles including the suprahyoid muscles such as the geniohyoid, mylohyoid, and hyoglossus elevate with the hyoid while
the thyrohyoid, suprahyoid, and the long pharyngeal muscles
(111) pull the larynx upward toward the hyoid to assist in
epiglottic inversion as the arytenoid cartilages are pulled forward underneath the epiglottis to assist with closing the upper
entry to the vestibule. This motion is coincident with posterior
motion of the posterior tongue to propel the food into the
posterior oropharynx and provide downward pressure coincident with pharyngeal contraction. Although the use of suprahyoid and thyrohyoid muscles to elevate the hyo-laryngeal
complex have been examined (22, 23), the interaction of the
simultaneous motion of tongue posterior pressure and hyolaryngeal motions have not been examined for biomechanical
interactions. The anterior elevation of the larynx is thought to
add to relaxation of the upper esophageal sphincter to allow the
food and liquid to clear from the hypopharynx (111–113).
However, the coincident motions of tongue retraction along
with hyo-laryngeal elevation and pharyngeal squeezing have
not yet been modeled to establish the muscle contraction
timing and forces needed to effectively clear the bolus from the
hypopharynx during swallowing.
RELATIONSHIP BETWEEN RESPIRATION AND SWALLOWING
Respiration and swallowing have opposing biomechanical
effects on upper airway musculature; dilation for inspiration to
allow unobstructed air intake into the lungs contrasted with
oropharyngeal compression for squeezing the bolus through
the pharynx and the upper esophageal sphincter. The control of
these two systems is coordinated in neurons involved in these
two integrative systems in the brain stem (60). For example, a
neuron contained in the nucleus tractus solitarius showing
cyclic depolarization with inspiration, altered its firing pattern
during fictive swallowing to be coincident with phases of
swallowing (60). Swallowing interrupts the respiratory cycle
during an apneic period in the pharyngeal phase when the
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muscle that has a similar action regardless of the tasks being
performed. Posterior cricoarytenoid muscle activation is consistently associated with vocal fold opening for all tasks including inspiration, sniff, and cough (17, 115). Three compartments have been proposed for this muscle: vertical, oblique,
and horizontal in the canine (122). The oblique and horizontal
compartments may contribute to abduction for inspiration.
Activation of the vertical compartment could account for
rocking backward to oppose the tensing and shortening actions
of the cricothyroid and thyroarytenoid in high-pitched voice
production (122).
Each of the laryngeal muscles acts interactively with other
muscles during different tasks. For example, the cricothyroid
muscle, which serves to lengthen the vocal folds, may augment
vocal fold opening when it cocontracts with the posterior
cricoarytenoid muscle during inspiration and sniff in humans
(3, 115). However, cricothyroid contraction has not consistently been associated with changes in vocal fold adduction or
abduction (157–159). The three adductor muscles (the thyroarytenoid, lateral cricoarytenoid, and interarytenoid) interact
during vocal fold adduction. The most information is available
on the thyroarytenoid muscle, likely due to ease of access to
the main body of the vocal fold via needle insertion through the
cricothyroid membrane. Both the thyroarytenoid and lateral
cricoarytenoid are active during the vocal fold closure phase of
cough but are not as clearly associated with vocal fold closing
during speech (115). Possibly the use of the laryngeal muscles
for speech is developed somewhat idiosyncratically by infants
as they learn to emulate the auditory targets of speech sounds
from the language in their environment. Perhaps muscle activation patterns for speech are more individualized due to
implicit learning while muscle patterning during respiration,
cough, and swallow are under the control of innate central
pattern generators in the brain stem.
Several constraints have limited human research on the
laryngeal muscles and laryngeal biomechanics. In humans, the
larynx can only be visualized with a transoral rigid laryngoscope prohibiting speech, cough, and swallow or with nasoendoscopes for only a few minutes at a time. Electromyographic
access to the laryngeal muscles requires insertions of needles
between the cricoid and thyroid cartilages (50) and verification
gestures to identify muscle location (50, 86). Although visualization and placement via a nasoendoscope allows visualization of electrode insertion (77), anesthesia is required, thus
altering muscle function. Endoscopic techniques allow recording from the posterior cricoarytenoid, although these are less
accurate than hooked wire electrodes (39). Finally, during
swallowing the larynx moves markedly and electrodes are
easily dislodged. As a result, relatively few studies of laryngeal
electromyography during speech, respiration, and cough have
been conducted in humans (115).
•
Review
298
Upper Airway Function in Breathing and Swallowing
larynx is closed, and the bolus is moved through the pharynx
into the esophagus similarly in mammals (93) and humans
(110). Further, swallowing also causes a resetting of the respiratory rhythm demonstrating a modification of respiratory
cycling by swallowing (110). As swallowing onset close to the
onset of inspiration can increase the risk of aspiration of
substances with the coincidence of dilation and compression in
the upper airway, the relationship between these two systems
needs to be well controlled for survival (93).
ACKNOWLEDGMENTS
This work was supported by National Institutes of Health grants DC
007692, U54 NS065701, and 1R43 DC012754-01.
DISCLOSURES
Dr. Ludlow serves as a consultant to Passy Muir, Inc., and is an inventor on
2 patents for devices for treating swallowing disorders.
Author contributions: R.F.F. and C.L.L. prepared figures; R.F.F. and C.L.L.
drafted manuscript; R.F.F. and C.L.L. edited and revised manuscript; R.F.F.
and C.L.L. approved final version of manuscript.
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