Muscles of Breathing: Development, Function,

and Patterns of Activation

Jason Q. Pilarski,1 James C. Leiter,2 and Ralph F. Fregosi*3

ABSTRACT
This review is a comprehensive description of all muscles that assist lung inflation or deflation in
any way. The developmental origin, anatomical orientation, mechanical action, innervation, and
pattern of activation are described for each respiratory muscle fulfilling this broad definition. In
addition, the circumstances in which each muscle is called upon to assist ventilation are discussed.
The number of “respiratory” muscles is large, and the coordination of respiratory muscles with
“nonrespiratory” muscles and in nonrespiratory activities is complex—commensurate with the di-
versity of activities that humans pursue, including sleep (27). The capacity for speech and adoption
of the bipedal posture in human evolution has resulted in patterns of respiratory muscle activation
that differ significantly from most other animals. A disproportionate number of respiratory muscles
affect the nose, mouth, pharynx, and larynx, reflecting the vital importance of coordinated muscle
activity to control upper airway patency during both wakefulness and sleep. The upright posture
has freed the hands from locomotor functions, but the evolutionary history and ontogeny of fore-
limb muscles pervades the patterns of activation and the forces generated by these muscles during
breathing. The distinction between respiratory and nonrespiratory muscles is artificial, as many
“nonrespiratory” muscles can augment breathing under conditions of high ventilator demand. Un-
derstanding the ontogeny, innervation, activation patterns, and functions of respiratory muscles
is clinically useful, particularly in sleep medicine. Detailed explorations of how the nervous sys-
tem controls the multiple muscles required for successful completion of respiratory behaviors will
continue to be a fruitful area of investigation. © 2019 American Physiological Society. Compr
Physiol 9:1025-1080, 2019.

Didactic synopsis 6. Studying the development, function, and neural control of

Major teaching points
1. Before brainstem respiratory neurons make contact with
developing respiratory muscle motor neurons, the CNS
generates rhythmic spontaneous neural activity (rSNA),
which may underpin development of the circuits respon-
sible for rhythmic activation of the motor neurons, and
hence the breathing muscles.
2. In fully developed humans, there are approximately 63
muscles (most paired bilaterally) with a documented role
in breathing, representing roughly 20% of the 320 pairs of
human skeletal muscles.
3. Contraction of breathing muscles generates force, leading
to changes in the size of the rib cage, lungs, and upper
airway.
4. Though breathing occurs with little awareness, it involves
the breathing muscles forms the basis for understanding
breathing disorders.
Introduction
The purpose of this review is to provide a single source
of information on every muscle with a documented role in
breathing. We also hope that the information provided will
allow those outside the field to appreciate the complexity and
richness of this unique motor system, and perhaps encour-
age them to work with this system. We have emphasized
the neural innervation and respiration-related actions of each
* Correspondence to fregosi@email.arizona.edu
1 Department of Biological and Dental Sciences, Idaho State
University Pocatello, Idaho, USA
2 Department of Molecular and Systems Biology, The Geisel School of

highly complex and poorly understood neural circuits that Medicine at Dartmouth, Lebanon, New Hampshire, USA
are largely located in the medulla oblongata. 3 Departments of Physiology and Neuroscience, The University of

Arizona, Tucson, Arizona, USA

5. The recruitment, timing, and intensity of breathing muscle Published online, July 2019 (comprehensivephysiology.com)
contractions is adjusted automatically in activities ranging DOI: 10.1002/cphy.c180008
from sleep to maximal exercise. Copyright © American Physiological Society.

Volume 9, July 2019 1025

The Muscles of Breathing
“respiratory” muscle, and we have emphasized the coordina-
tion with other “nonrespiratory” muscles and nonrespiratory
activities. We will show that the distinction between respi-
ratory and nonrespiratory muscles is slightly artificial and
depends on the physiological context in which the activity
takes place so that many nonrespiratory muscles augment
or support respiration and many nominally respiratory mus-
cles (even the diaphragm) are required to perform nonres-
piratory functions (27). We have considered how the neural
innervation and activation patterns of the respiratory muscles
develop; we have reviewed their anatomy and discharge pat-
terns in detail; and we have addressed their function during
sleep, as an example of how changing central nervous sys-
tem state can alter the activity of the muscles. The focus is
mainly on mammals, as the comparative physiology of the
breathing musculature is complex and beyond the scope of
this review. We write this from an admittedly neurocentric
point of view in which our main focus is on the neural control
of respiratory motor output; thus, information on the detailed
structure and mechanical properties of the muscle fibers will
not be considered here, as many excellent reviews are avail-
able (12, 173, 249, 350, 406).
How does one define a “muscle of breathing”? The sim-
plest definition, and the one that drives this review, is that
any muscle that assists lung inflation or deflation qualifies.
This includes a primary role, such as expansion of the tho-
rax by the external intercostal muscles; a supportive role,
such as stabilization of the thorax by the quadratus lumbo-
rum; or a valving function that regulates airflow resistance,
such as laryngeal, pharyngeal, or facial muscles. For certain
activities, we have expanded the definition of “respiratory”
as nonrespiratory muscles are recruited to support or regu-
late respiratory function. We have presented the respiratory
muscles in anatomical groupings rather than grouping them
as pump muscles (the main respiratory muscles of the tho-
rax), accessory muscles (generally upper airway muscles and
muscles connected to the shoulder girdle), and then a group
of muscles that lack activity during eupnea but are called
upon to increase respiratory output when respiratory drive is
increased. Nevertheless, we do use the more functional clas-
sifications (i.e., pump, accessory, and upper airway) when it
is necessary for clarity or emphasis. Understanding how the
neural innervation develops and ultimately organizes respi-
ratory muscle activity into a mature, functional system is
important for understanding how neuromuscular disorders
will affect the function of respiratory muscles, and thus pul-
monary ventilation and regulation of blood gases and pH.
We also hope that a better understanding of the innervation
and mechanical contribution of all the breathing muscles to
pulmonary ventilation will provide a framework to under-
stand adaptations that restore altered function, or to train a
muscle that normally plays only a minor role in breathing
to play a more prominent role (e.g., following spinal cord
injury).
1026
Comprehensive Physiology
Embryonic Development of the Breathing
Musculature
All skeletal muscle, and therefore all breathing-related skele-
tal muscle, originates from mesoderm. Mesoderm initially
appears in humans during gastrulation near the start of the
third week of gestation. The early mesoderm is unsegmented
along its entire length and can be initially observed as a flat-
tened lateral strip relative to the midline (see Gasser et al.
(163) for a detailed description of the human embryo). As
Figure 1A (left panel) shows, the mesoderm layer can be
further divided (rostro-caudally) into prechordal, cranial, and
trunk mesoderm. Prechordal mesoderm lies anterior to the
notochord as well as beneath it. Over time, the prechordal
mesoderm will be displaced and integrated with the cranial
mesoderm to form several extraocular muscles with distinc-
tive muscle fiber-type characters (81,473). Cranial mesoderm
produces most of the muscles of the head and some of the
skull base. Some textbooks additionally refer to this special-
ized head mesoderm as preotic mesoderm, using the otic vesi-
cle as a convenient, but imprecise anatomical landmark (258).
Information regarding the differentiation of cranial mesoderm
has historically suffered from the absence of clear morpholog-
ical boundaries. However, recent biochemical and molecular
data reveal some of the cellular elements that identify unique
craniofacial muscle groups produced during early head and
neck development (45, 147) [and for reviews, see (322, 382)].
This area of research continues to advance using a variety
of clever phylogenetic and developmental techniques [see
(210,265,382)]. Nonetheless, the so-called preotic mesoderm
remains more or less anatomically irregular, and embryol-
ogists have previously described this tissue as subdivided
into unique quasi-segmented structures called somitomeres
(71, 258). Somitomeres are loosely organized into discs of
mesoderm situated bilaterally and beneath the neural tube
(Fig. 1A). Importantly, cranial somitomeres contribute to the
developing pharyngeal arch structures by distributing region-
specific streams of migrating mesoderm toward the endoderm
of the pharynx, which is shown in Figure 1A (right panel).
While the ontogenetic details of cranial mesodermal pop-
ulations continue to be elucidated, they clearly differ from
the mesoderm located in the neck (immediately postotic) and
in the trunk where the developing mesodermal layer is fur-
ther organized into clearly identifiable epithelialized segments
called somites. A model representation of somite positions,
their internal compartments, and some of the muscles they
produce is shown in Figure 1A to C (84). Due to the collec-
tive involvement of cranial, neck, and trunk musculature in
breathing behaviors, the embryological development of the
ventilatory apparatus is a diverse and complex association
derived from both cranial and trunk mesoderm, each with dis-
tinct organizational programs (282, 302, 479). Additionally,
ectodermal germ layer derivatives contribute to the assembly
of the respiratory musculoskeletal system as they generate
Volume 9, July 2019
 Caudal Rostral
(A) Prechordal plate and (B) Epaxial
prechordal mesoderm Somites
Hypaxial
Cranial and (future mouth region)
Cardiogenic Cranial
pharyngeal mesoderm 5 4 3 2 1 Unsegmented cranial, prechordal
33.... bones
mesoderm (a.k.a., and pharyngeal mesoderm

Volume 9, July 2019

unsegmented Trunk, limbs,
Tongue Extraocular
somitomeres) diaphragm, etc.
muscles; muscles;
Comprehensive Physiology

1 1 1 cranial nerves 3, 4, and 6

cranial
2 2 2 1st arch
nerve X
and Xll (jaw muscles; cranial nerve 5)
3 3 2nd arch
Cell migration Neck muscles;
4 4 (facial muscles; cranial nerve Vll)
Truck paraxial cranial nerve Xl

Neural tube
5 5 and cervical spinal nerves
mesoderm
6 6 3rd and 4th arch (pharynx and larynx and soft palate;
7 7 (C) cranial nerves lX and X)
Otic
placodes 1
Somites
2 Amnion
(segmented)

Pharyngeal arches
3 Neural tube

Notochord
Primitive streak
(gastrulation) 4 Ectoderm

d,m
N S im
Rostral s
Early 3rd week 4th week Somatic Co
and Endoderm elo
m
splanchnic
Caudal
lateral
Dorsal
mesoderm
Cut edge of amnion Week 4 Yolk sac

Ventral

Figure 1 Embryological origin of the muscles of breathing in vertebrates. Panel A shows the development of cranial and trunk mesoderm in a conceptualized embryo. The embryo is shown
in a superior view with the amnion cut away and the overlying ectoderm removed, except for the neural tube in the right panel. The primordial myoblasts are shown in black (cranial and
pharyngeal mesoderm) and red (trunk mesoderm), which collectively contribute to the head, neck, and trunk musculature during the third and fourth week of development. This panel also shows
relative positions of the prechordal plate and associated mesoderm and the cardiogenic mesoderm, as well as structures involved in the events of gastrulation, such as the primitive streak.
The thick arrow pointing caudally (right side of Panel A) depicts the regression of the primitive streak as somites are being added and the notochord is lengthening toward the tail end. Note
that the neural tube is forming simultaneously and lies over the notochord dorsoventrally. The notochord extends rostrally to approximately the prechordal plate. The otic placodes (yellow oval)
contribute to the developing ear as a thickening of the ectoderm and are gross anatomical characters separating the head mesoderm (a.k.a. somitomeres) from the rostral somites. The pharyngeal
mesoderm is shown in gray as it is forming pharyngeal arches from migratory myoblasts coursing ventrally from the cranial mesoderm (black arrows) and neural crest cells (not shown). (B) Lateral
view of developing muscles from unsegmented cranial and segmented trunk mesoderm near embryonic week 4. Arrows indicate movements of myoblasts and cranial nerve associations from
pharyngeal mesoderm and neural crest cell-derived ectomesenchyme. (C) Cross section of the postgastrulation trilaminal disc near embryonic week 4. The approximate rostrocaudal plane
is shown with broken black lines near the second somite in A. At this stage, the neural tube has begun to fold and will meet in the sagittal plane while the mesoderm is differentiating into
region-specific structures laterally. The dorsal aspect of the somite or dermomyotome (d, m) will produce the connective tissue of the dermis (d) and skeletal muscles (m), and the ventral somite or
sclerotome (s) will produce most of the axial skeleton. The derivatives of the muscles and connective tissues of the head are a combination of cranial mesoderm and ectomesenchyme that create
the pharyngeal arches (gray overlapping circles), as well as occipital somites (not shown). Human embryos have approximately 33 somite pairs. N = notochord; S = somite; NCC = neural crest
cells; im = intermediate mesoderm; d = dermomyotome; m = myotome; s = sclerotome. Modified, with permission, from (72). See text for more detail.

1027
The Muscles of Breathing
The Muscles of Breathing
most of the connective tissues of the head, including some of
the bone (296, 297).
By far the largest myogenic source for the developing
breathing apparatus is the segmented paraxial mesoderm (seg-
mented = somites; paraxial = beside the long axis). Beginning
near the level of the otic vesicle, paraxial mesoderm is posi-
tioned on both sides of the developing notochord and neural
tube and differentiates in a rostro-caudal orientation as com-
pact blocks of somite mesoderm surrounded by columnar
epithelial cells (Fig. 1). Somites contain several mesoder-
mal cell populations, including the sclerotome and dermomy-
otome (dermatome + myotome; shown in panel Fig. 1C). Fate
mapping studies have revealed that the dermatome contributes
tissue to the dermis, and the myotome will become the epax-
ial (e.g., back muscles) and hypaxial (e.g., muscles ventral
to the vertebral axis) muscle groups depending on the spe-
cific somite territory within the myotome (59, 222). Unlike
epaxial muscle development, the myoblasts of the hypaxial
somites often migrate, and they will establish limb muscula-
ture and the primary pump musculature for breathing, includ-
ing the intercostal, abdominal, and diaphragm muscles (see
the following text for more detail on the development of the
diaphragm and Fig. 1B for a fate mapping schematic).
Within this arrangement, the most rostral somites, which
are immediately caudal to the otic vesicle (i.e., postotic), are
unique and are referred to as the occipital somites. The occip-
ital somites abandoned their previous role in stabilization of
the axial skeleton and are instead incorporated into the head
and neck of the craniates (162). From a phylogenetic perspec-
tive, these somites have been adapted as accessory breathing
muscles of the neck (e.g., sternocleidomastoid and trapezius),
and streams of myoblastic stem cells from this area also invade
the caudal pharyngeal arches generating accessory respiratory
muscles of the pharynx and larynx (222). However, recent evi-
dence suggests that the lateral plate mesoderm, which lies next
to these anterior somites (Fig. 1C), may also help generate the
neck muscles (436). These data are consistent with the posi-
tion of the occipital myotomes between the head and trunk
mesoderm, and possibly represent an evolutionary transition
in which the rostral trunk somites were incorporated into the
head and neck to form a hybrid tissue with features attributable
to the trunk and cranium. In the chick embryo, for example,
the neck musculature exhibits both trunk specific and cranial
specific genetic markers (436).
The occipital somites are responsible for generating the
striated muscle of the tongue (90,197,222,319). The tongue is
a muscular organ composed of four intrinsic and four extrinsic
skeletal muscles (see Table 1). Recent work in rodent models
(16-21,150,151,153,155,156,235,236,239,351,364,378,395,
455, 485) and now human subjects (128, 288, 329) indicates
that several tongue muscles are recruited during breathing to
dilate and stiffen the pharyngeal airway. While the tongue is
regionally a part of the head and enclosed within the oral cav-
ity (anterior 2/3) and the oropharynx (posterior 1/3), all the
tongue musculature is derived from mesoderm from the paired
occipital somites and not the cranial somitomeres (for a review
1028
Comprehensive Physiology
see) (353). As Figure 1B depicts, this contrasts with most other
skeletal muscles of the cranium, such as the muscles of the
jaw and face, which are derived from the pharyngeal arch and
cranial mesoderm (322). The myoblast cells from the occipital
myotomes are thought to express Pax-3 transcription factor,
similar to migrating trunk (limb) myoblasts, but distinct from
cranial mesoderm (see the following text). These myoblast
cells move bilaterally from the anterior caudal hindbrain to
the floor of the developing pharynx to form a mesenchymal
band called the “hypoglossal chord” (285). The formation of
the hypoglossal chord occurs from embryonic weeks 5 to 7 in
humans (325). Most of the extrinsic tongue muscles, which
are involved in the control of pharyngeal resistance and com-
pliance (see Table 1), are similarly derived from infiltration
by migratory myoblasts of the occipital myotomes (197). A
possible exception to this pattern of occipital developmental
origin may be the palatoglossus muscle, a palatal and extrin-
sic tongue muscle, which is innervated by the vagus nerve,
instead of the hypoglossal nerve, and thus is likely of pharyn-
geal arch origin.
Perhaps the most enigmatic and irregular mesodermal
components of the breathing apparatus are the cranial parax-
ial mesoderm (also known as preotic paraxial mesoderm),
which are responsible for the development of facial, jaw, and
pharyngeal muscles, which, like tongue muscles, stiffen and
widen the upper airway when activated (discussed below).
These cranial muscle groups are products of the head meso-
derm that do not epithelialize to form proper somites as shown
in Figure 1B (184). Instead, this population of mesodermal
cells produces myogenic precursors in the form of diminutive
discs that seem to originate adjacent to the developing brain
and the prechordal plate [see Fig. 1A and (302)]. Some of
these founder myoblastic cells infiltrate the pharyngeal arches
near embryonic day eight in the mouse embryo (184,316) and
during the third week of gestation in humans (300).
The final source of progenitor cells for the breathing-
related musculoskeletal apparatus is ectoderm. Typically,
ectoderm forms the nervous system, including both central
and peripheral components, but plays no role in the genesis
of musculoskeletal derivatives. However, the ectodermally
derived cranial neural crest cells that invade the pharyngeal
arches are unique pluripotent cells, known as neural crest
mesenchyme or ectomesenchyme, and these cells possess a
special phenotypic repertoire in that they generate the cran-
iofacial connective tissues and bones of the viscerocranium
[for a review, see (322)]. Cranial neural crest cells migrate to
the pharyngeal arches in a path originating from the develop-
ing hindbrain and mix with the resident cranial and occipital
paraxial mesoderm discussed above. These neural crest cells
will create the connective tissue (e.g., tendons, epimysium,
etc.) for the craniofacial and hypobranchial musculature. Neu-
ral crest cells also contribute to the migration, pattern, and
shape of these muscle primordia (142, 290, 320, 321, 368).
Cooperation between the migrating neural crest cells and
migrating cranial mesoderm is also observed in the details
of cranial nerve innervation of the breathing-related muscles.
Volume 9, July 2019
Comprehensive Physiology The Muscles of Breathing

Table 1 Skeletal Muscles with a Documented Role in Breathing, as Discussed in the Text

Active during
Location of Active Eupnea in
Region Muscle Origin Insertion Innervation motoneurons phase humans

Nose
Procerus Nasal bones Cartilage, skin or Buccal branch of Caudal ventrolateral Inspiration Minimal to no
and/or cartilage connective tissue of facial nerve (VII) pontine tegmentum activity
(see text) external nose, and (VII nucleus)
or other nasal
Alar nasalis muscles (see text) Buccal branch of Caudal ventrolateral Inspiration Minimal to no
(dilator naris)∗ facial nerve (VII) pontine tegmentum activity
(VII nucleus)
Transverse Buccal branch of Caudal ventrolateral Inspiration Minimal to no
nasalis facial nerve (VII) pontine tegmentum activity
(VII nucleus)
Depressor Buccal branch of Caudal ventrolateral Expiration Minimal to no
septi nasi facial nerve (VII) pontine tegmentum activity
(VII nucleus)
Levator labii Buccal branch of Caudal ventrolateral Inspiration Minimal to no
superioris facial nerve (VII) pontine tegmentum activity
alaeque nasi (VII nucleus)
Apicis nasi Buccal branch of Caudal ventrolateral Inspiration Minimal to no
facial nerve (VII) pontine tegmentum activity
(VII nucleus)
Head and neck
Masseter Superficial head, Lateral and inferior Mandibular Mid pons Inspiration No
zygomatic bone surface of mandible division of
trigeminal
Deep head, Mandibular ramus Nerve (V)
zygomatic arch
Upper Occipital bone, Spine of scapula; Spinal accessory Nucleus ambiguuus Inspiration Some tonic
trapezius% spinous processes clavicle nerve (XI) and and C3-C4 and or phasic
of C7-C12 spinal nerves C3 activity
vertebrae; nuchal and C4
ligament
Sternocleid- Manubrium of Mastoid process Spinal accessory Nucleus ambiguuus Inspiration Rarely
omastoid% sternum; clavicle nerve (XI), ventral and C1-C2
ramus of C2
and C3
Scalenes Transverse First or second ribs Ventral rami of C3-C8 Inspiration Yes, but
processes of C3-C8 spinal inconsistent
cervical vertebrae nerves
C2-C7
Medial Deep head, lateral Medial surface of Mandibular Mid pons Inspiration No
pterygoid pterygoid plate the mandible division of
trigeminal nerve
Superficial head,
tuberosity of the
maxilla and
pyramidal process
of the palatine bone
Lateral Superior head, Cartilage of Mandibular Mid pons Inspiration No
pterygoid infratemporal temporomandibular division of
surface of the joint trigeminal nerve
sphenoid bone
Inferior head, Condyloid process
lateral pterygoid of mandible
plate

(Continued )

Volume 9, July 2019 1029

The Muscles of Breathing Comprehensive Physiology

Table 1 (Continued )

Active during
Location of Active Eupnea in
Region Muscle Origin Insertion Innervation motoneurons phase humans

Tongue
Genioglossus Mental surface of Base of tongue; Medial branch of Lateral division of Inspiration, Some tonic
the mandible hyoid bone; and hypoglossal nerve the ventromedial XII some activity;
connective tissue (XII) nucleus expiration phasic
(see text) activity rare
Hyoglossus Hyoid bone Lateral edges of Lateral branch of Dorsolateral Inspiration No
tongue blade hypoglossal nerve compartment of XII
(XII) nucleus
Styloglossus Anterior and Ipsilateral Lateral branch of Dorsolateral Inspiration No
lateral surfaces of hyoglossus; Hypoglossal nerve compartment of XII
styloid process; inferior (XII) nucleus
stylomandibular longitudinalis
ligament
Palatoglossus# Palatine Lateral edges of Vagus nerve (X) Nucleus ambiguus, Inspiration Yes
aponeurosis tongue blade dorsolateral XII (1)
Inferior ∗ ∗ Lateral branch of Widely distributed Inspiration No
longitudinalis hypoglossal nerve throughout XII
(XII) nucleus
Superior ∗ ∗ Lateral branch of Widely distributed Inspiration No
longitudinalis hypoglossal nerve throughout XII
(XII) nucleus
Transversus ∗ ∗ Medial branch of Widely distributed Inspiration No
hypoglossal nerve throughout XII
(XII) nucleus
Verticalis ∗ Complex—see ∗ Complex—see Medial branch of Widely distributed Inspiration No
text text hypoglossal nerve throughout XII
(XII) nucleus
Soft palate
Levator veli Temporal bone Midline of velum Vagus Nerve (X) Nucleus ambiguus Inspiration Inconsistent
palatini and cartilage of (2, 3) and retrofacial and
auditory tube nucleus expiration
Tensor veli medial pterygoid Palatine Mandibular branch rostral ventromedial Inspiration Yes
palatini plate; auditory aponeurosis and of trigeminal nerve division of V motor
tube bone (V) nucleus (4)
Musculus Fibers are Within uvula Vagus nerve (X)∗∗ Nucleus ambiguus Inspiration No
uvulae contained within and retrofacial
uvula nucleus
Suprahyoid
Digastric Mandible Hyoid Mylohyoid branch Dorsomedial Inspiration Unknown
(anterior belly) of the trigeminal trigeminal nucleus (6)
nerve (V) (5), pons
Digastric Mastoid process Hyoid Auricular branch of Facial nucleus (VII), ? Unknown
(posterior belly) facial nerve (VII) pons
Geniohyoid Mandible Anterior surface Hypoglossal nerve Ventral division of Inspiration Yes
of hyoid (XII) the ventromedial XII
nucleus, C1
Mylohyoid Mandible Hyoid Mylohyoid branch Trigeminal nucleus Inspiration Yes
of the trigeminal (V), pons
nerve (V)
Stylohyoid Styloid process Hyoid Mandibular branch Dorsomedial VII Inspiration Unknown
of facial nerve (VII) nucleus, pons (7)

1030 Volume 9, July 2019

Comprehensive Physiology The Muscles of Breathing

Table 1 (Continued )

Active during
Location of Active Eupnea in
Region Muscle Origin Insertion Innervation motoneurons phase humans

Infrahyoid
Sternothyroid Posterior Thyroid cartilage Ansa Cervicalis C1-C2 Inspiration, Unknown
manubrium of some
sternum and first rib expiration
(8)
Sternohyoid medial, posterior Hyoid Ansa Cervicalis C1-C2 Inspiratory Unknown
surface of clavicle; (9)
sterno-clavicular
ligament;
manubrium of
sternum
Thyrohyoid Thyroid cartilage Greater horn of the Hypoglossal nerve XII nucleus, C1 Inconsistent Unknown
hyoid bone and Ansa cervicalis (10)
Omohyoid (inferior Upper border of clavicle Ansa cervicalis, C1-C2 Inspiration Unknown
belly) scapula including the (11)
superior ramus of
ansa cervicalis
(superior belly) Clavicle Hyoid
Pharynx
Superior pharyngeal Medial pterygoid Pharyngeal raphe Vagus (X), via Nucleus ambiguus Tonic, Yes
constrictor plate, and occiput pharyngeal plexus expiratory
pterygomandibular
raphe, and
mandible
Middle pharyngeal Hyoid and Medial portion of Vagus (X), via Nucleus ambiguus Expiratory Minimal
constrictor stylohyoid ligament posterior pharyngeal plexus
pharyngeal raphe
Inferior pharyngeal Superior parts, Pharyngeal raphe Vagus (X), via Nucleus ambiguus Tonic, Minimal
constrictor thyroid cartilage; pharyngeal plexus∗ expiratory
inferior parts,
cricoid cartilage
Palatopharyngeus Posterior fascicle, Posterior border of Vagus (X), via Nucleus ambiguus Inspiration Yes
posterior soft thyroid cartilage pharyngeal plexus,
palate; anterior and accessory
fascicle, posterior nerve (XI)
surface of hard
palate
Stylopharangeus Styloid process Posterior edge of Glossopharyngeal Nucleus ambiguus Inspiration Unknown
thyroid cartilage; nerve (IX) (14)
fibers of
palatopharyngeus
and constrictors
Salpingopharyngeus Medial, Posterior fascicle of Vagus (X), via Nucleus ambiguus Inspiration Unknown
cartilaginous palatopharyngeus pharyngeal plexus (13)
section of
Eustachian tube
Larynx
Posterior Posterior surface of Lateral belly, Vagus (X), via Caudal nucleus Inspiration Yes
cricoarytenoid cricoid cartilage ipsilateral arytenoid recurrent laryngeal ambiguus and lesser
muscle; medial nerve role in
belly, ipsilateral expiration
arytenoid cartilage (16)

(Continued )

Volume 9, July 2019 1031

The Muscles of Breathing Comprehensive Physiology

Table 1 (Continued )

Active during
Location of Active Eupnea in
Region Muscle Origin Insertion Innervation motoneurons phase humans

Lateral Ipsilateral cricoid Muscular portion Vagus (X), via Caudal nucleus Inspiration No
cricoarytenoid cartilage of the arytenoid anterior terminal ambiguus
cartilage division of the
recurrent laryngeal
nerve
Transverse Lateral border of Lateral border of Vagus (X), via Caudal nucleus Expiration## Yes
arytenoid arytenoid contralateral recurrent laryngeal ambiguus
cartilage arytenoid nerve and internal
cartilage laryngeal nerve
Cricothyroid Anterolateral Inferior horn of Vagus (X), via the Rostral nucleus Inspiration Yes
aspect of cricoid thyroid cartilage external branch of ambiguus, dorsal and
cartilage superior laryngeal motor nucleus of X expiration
nerve (15)
Thyroarytenoid Lower half of Anterior surfaces Vagus (X), via Caudal nucleus Inspiration Yes
thyroid cartilage of arytenoid recurrent laryngeal ambiguus and
cartilage nerve expiration
Oblique arytenoid Base of arytenoid Apex of Vagus (X), via Caudal nucleus Expiration## Yes
cartilage contralateral recurrent laryngeal ambiguus
arytenoid nerve
cartilage
Epiglottic Muscle Apex of arytenoid Lateral border of Vagus (X), via Caudal nucleus Unknown Unknown
(“aryepiglotticus”) cartilage epiglottis recurrent laryngeal ambiguus
nerve
Thorax
External Ribs 1-11 Ribs 2-12 Intercostal nerves T1-T11 Inspiration Yes
intercostals
Internal ribs 2-12 Ribs 1-11 Inntercostal nerves T1-T11 Expiration Yes
intercostals
Transversus dorsal surface of Costal cartilages Intercostal nerve T8-T11 Expiration Yes (17)
Thoracis Xiphoid process, 2-6
(“Triangularis and caudal region
sterni”) of dorsal sternum
Innermost Inner surface of rib Inner surface of Intercostal nerves T1-T11 (Highly Unknown Unknown
intercostals a rib 1-3 spaces variable presence)
caudal to the rib
of origin
Pectoralis major Clavicular head, Bicipital groove Lateral and medial C5-T1 Inspiration No
anterior border of of anteromedial pectoral nerves
clavicle; humerus
sternocostal head,
anterior surface of
sternum, upper six
costal cartilages,
and aponeurosis
of external oblique
muscle
Pectoralis minor costochondral Medial and Lateral and medial C6-C8 Unknown Unknown
junction of ribs 3-5 superior surface pectoral nerves
of scapula
Serratus anterior ribs 1-8 or 9 medial border of Long thoracic nerve C5-C7 Inspiration, No
scapula and early
thoracic expiration
vertebrae

1032 Volume 9, July 2019

Comprehensive Physiology The Muscles of Breathing

Table 1 (Continued )

Active during
Location of Active Eupnea in
Region Muscle Origin Insertion Innervation motoneurons phase humans

Subclavius Inner surface of Subclavian Brachial plexus C5-C6 Unknown Unknown

first ribs groove of
clavicle
Subcostalis inner surface of Inner surface of Intercostal nerves T1-T11 Unknown Unknown
ribs (when a rib 1-3 spaces (highly
present, see text) caudal variable
presence)
Abdomen
Diaphragm Costal region; Central tendon Phrenic nerve C3-C5 Inspiration Yes
lower six ribs
(7-12)
Vertebral region; Central tendon Phrenic nerve
crus of L1-L3 and
arcuate ligaments
sternal region; Central tendon Phrenic nerve
posterior surface
of xyphoid
process of sternum
External oblique Inferior margins of Bundles from Ventral spinal T5-T12 Expiration, Minimal,
ribs 5-12 lower ribs, iliac nerves T7-L1 early mostly in
crest rostral inspiratory standing
bundles, linea posture
alba
Internal oblique Iliac crest; Ribs 10-12 and Ventral spinal T7-L1 Expiration, Minimal,
thoracolumbar linea alba nerves T6-L2 early mostly in
fascia, and inspiratory standing
inguinal ligament posture
Transverse Inguinal ligament; Ribs 10-12; linea Ventral spinal T7-L1 Expiration, Minimal,
abdominus iliac crest; alba nerves T6-L2 early mostly in
cartilage of lower inspiratory standing
6 ribs posture
Rectus abdominus Crest of pubic Xiphoid process; Ventral spinal T5-T12 Expiration, Minimal,
bone costal cartilages nerves T7-L1 early mostly in
of ribs 5-7 inspiratory standing
posture
Quadratus Iliac crest and Inferior border of T12-L4 T7-L4 Inspiration Yes%
lumborum ilioloumbar lower-most rib (18)
ligament
Back
Levatore costae Transverse Caudal rib, or Dorsal rami of T1-T12 Inspiration Yes, when
processes of ribs thoracic Spinal standing
T7-T11 nerves
Latissimus dorsi spinous processes Intertubercular Thoraco-dorsal C6-C8 Inspiration Minimal
of T7 to L5 groove of nerve, formed by (and forced
vertebrae; the humerus branches of expiration)
thoracolumbar C6-C8 spinal
fascia; iliac crest; nerves
bottom four ribs;
inferior angle of
scapula

(Continued )

Volume 9, July 2019 1033

The Muscles of Breathing Comprehensive Physiology

Table 1 (Continued )

Active during
Location of Active Eupnea in
Region Muscle Origin Insertion Innervation motoneurons phase humans

Erector spinae sacral crest; Ribs 3-12, but Posterior rami of T1-12, L1-L5, S1-S3 Inspiration No
spinous processes see text spinal nerve
of the T11-T12;
each of the lumbar
vertebrae

∗, Some authors consider these to be separate muscles

%, Whether or not the spinal innervation is sensory or both sensory and motor is unsettled
&, Anterior portion, C4-C6; medial portion, C3-C8; posterior portion, C6-C8
#, Sometimes considered to be a palatal muscle
∗∗, Cranial nerve IX may also supply some motor innervation
##, As described in text, whether recorded activity was from the transverse or oblique arytenoid could not be confirmed
%%, No data in human subjects
1. (413)
2. (450)
3. (157)
4. (244)
5. (298)
6. Anesthetized neonatal rats (380)
7. Anesthetized rabbits (373)
8. Anesthetized rabbit (372)
9. Various animal models (see text)
10. Anesthetized dogs (447)
11. Anesthetized monkeys (136)
12. Some evidence that there is also innervation via the recurrent laryngeal nerve and/or the superior laryngeal nerve (381)
13. Anesthetized rabbits (373)
14. Awake goats (144)
15. (340)
16. Expiratory activity in dogs (251)
17. Present in standing, but not supine human subjects (143)
18. Data from an anesthetized rabbit (47)
Note: The muscles are grouped by anatomical region. The nerve innervating each muscle, and the location of the motor neurons are also provided.
The active phase indicates whether the activity is primarily inspiratory or expiratory, and we also indicate whether or not the muscle is active in
eupnea. All anatomical data is, with permission, from the digital version of Gray’s Anatomy (421), or from references provided in the text. The
active phase and eupneic activity refer to observations in human subjects, unless indicated otherwise.

For example, the cranial nerves that innervate the larynx, phar-
ynx, and facial muscles, that is, cranial nerves X, IX, and VII,
are directed to their targets by the neural crest cells in a pre-
cise manner according to these muscle-arch relationships (88).
Similarly, so-called circumpharyngeal neural crest cells may
guide the hypoglossal nerve, as well as the lingual myoblasts,
to their final locations (266). However, this topic needs more
attention as Mackenzie et al., (285) showed, using chick/quail
chimeras, that myoblast migration was independent of neural
crest cell influence.
Arguably, the most unusual anatomical aspect of mam-
malian breathing is the distinct (autapomorphic), dome-
shaped muscular diaphragm—the major respiratory pump
muscle in most if not all mammals. The diaphragm is the
muscle most responsible for the large volume changes of
the abdominal and thoracic cavities and the lungs during
inspiration, although many other body wall muscles also con-
tribute to this pumping behavior (see Table 1). For this reason,
the embryological origin of the diaphragm warrants special
attention. Moreover, the diaphragm exhibits a number of
breathing-related birth defects that are a direct result of errors
in the course of its embryonic development.
The thin dome-shaped muscular diaphragm develops dur-
ing the fourth through the tenth week of human gestation as a
result of the union of three principal mesodermal sources
(301). One of the most important early structures of the
developing diaphragm is the septum transversum. The sep-
tum transversum first appears near human gestational day 22
and is composed of a layer of cranial and cardiogenic meso-
derm (see Fig. 1A). The septum, along with the heart pri-
mordia, is located at the extreme rostral tip of the embryo
at this stage (131) and subsequently “descends” into the
lower thorax during embryonic head folding (weeks 3-4 in
humans). The septum transversum adheres to the ventral
and lateral body wall and extends in a shelf-like orienta-
tion, which is sandwiched between the liver and the heart
primordia. In this way, the septum transversum incompletely
divides the pleuro-pericardial cavity and likely contributes
to the connective tissue framework that eventually directs
muscle precursors from the hypaxial somitic buds to sites
within the diaphragm. Complete separation of the pleural and
peritoneal cavities occurs when additional mesodermal pro-
genitor cells penetrate and infiltrate the septum during late
gestation.

1034 Volume 9, July 2019

Comprehensive Physiology
Near the ventral aspect of the septum transversum’s new
location, between the pleural and the peritoneal cavities, two
so-called pleuroperitoneal folds also play an important role
in diaphragm morphogenesis. These folds are a union of
the pleuropericardial and pleuroperitoneal membranes and
appear to be an organizer for the proliferation and matu-
ration of myoblast cells that ultimately create the muscu-
lar diaphragm. The pleuroperitoneal folds are derived from
mesoderm that originates bilaterally from the dorsolateral
body wall where they remain attached while the medial edges
reach into the undivided coelomic cavity. In this way, the
pleuroperitoneal folds blend or fuse with the septum transver-
sum. In humans, this occurs between gestational weeks 4
to 6 (275). The pleuro-peritoneal structure eventually joins
with the esophageal connective tissue medioventrally, and by
gestational week 7, full separation of the thoracic and abdom-
inal cavity is finalized. It is this separation or rather lack
of separation that may lead to diaphragmatic birth defects
during early development. Several types of location-specific
congenital, diaphragmatic hernias can occur at the sites of
pleuro-peritoneal closure, and each is associated with del-
icate or thin regions of the muscle and/or connective tis-
sue [for a review, see (85) and (175)]. Congenital diaphrag-
matic hernias affect about 1 in 2500 newborns (423) and
require prompt medical attention since adequate inspira-
tory pressures to achieve tidal breathing cannot be gener-
ated without compete separation of thoracic and abdominal
cavities (196).
It is now well established that the myogenic lineage
of the mammalian diaphragm is derived from hypaxial
(trunk) somites, but they are not simply somitic extensions
of the thoracoabdominal body wall. Rather, diaphragmatic
development is closely associated with forelimb development
and the ability of muscle precursors to migrate long dis-
tances from the limb buds (57, 123, 124) [for reviews, see
(122, 208)]. Limb myoblasts multiply and depart from the
somitic myotomes to make their way among the lateral plate
mesoderm and invade the limb primordia. Similarly, diaphrag-
matic myoblasts, which are initially mixed with forelimb
tissue, are thought to diverge and migrate from their posi-
tion at the ventral lip of the cervical dermomyotome (i.e.,
somites C3-5) to populate the developing pleuroperitoneal
sheath (9, 14, 85, 285). This scenario is supported by studies
that show the diaphragm, as well as the limb musculature, fail
to develop in loss of function experiments that target migra-
tory muscle specific transcription factors for Pax3, formerly
called splotch, and c-Met (i.e., tyrosine receptor kinase),
yet the dorsal and lateral body wall musculature develop as
expected (41, 123, 430, 440). These molecular signals reflect
gene families that control epithelial to mesenchymal transi-
tions, differentiation, and target site identification, and may
lead to a unique developmental program that creates the mam-
malian diaphragm. Buchholtz et al. (62) suggest that Hox gene
expression in the midcervical region, where the muscle cells
of the diaphragm originate, is a specialized developmental
module distinct from the more rostral and caudal cervical
Volume 9, July 2019
The Muscles of Breathing
somites known to provide mesoderm for the head and neck
and the forelimbs, respectively.
Finally, the newly muscularized diaphragm travels poste-
riorly and inferiorly from the cervical region as the embryo
elongates, and the diaphragm reaches a temporary position
near the thorax by the sixth week of human gestation. By
the eighth embryonic week, the dorsal connection of the
diaphragm lengthens to reach the lumbar vertebrae. The
innervation of the muscular diaphragm reflects the travel-
ing muscle primordia of this tissue in both space and time.
The phrenic axons seem to coalesce into ventral rami of the
mid-cervical spinal cord (C3-C5) and subsequently invest the
pleuro-peritoneal folds as the embryo changes shape [see
Table 1 and Greer et al. (176) for a review]. This anatom-
ical scheme may explain the phenomenon of referred pain
originating from the diaphragm (Kehr’s sign) that is felt in
the shoulders and neck (417). It may also explain the close
coupling of rhythmic respiratory and muscular activities that
originate from the same muscular primordia and involve loco-
motion (39, 118, 126, 457) and especially upper extremity
movements in bipedal mammals. This coordination likely
reflects shared patterns of descending activation and ascend-
ing afferent inputs for breathing and locomotion (166, 167).
Respiratory-related muscle activation patterns
during embryonic and perinatal development
Fetal breathing movements (FBMs) are a ubiquitous feature
of all mammalian embryos and/or fetuses that have been
studied to date. These intrauterine body movements provide
information about fetal welfare, as well as details about the
maturation of the musculoskeletal and nervous systems.
FBMs have received a fair amount of attention due to the phys-
iological requirements for a seamless, yet prompt, conversion
from placental gas exchange (where FBMs play no role) to
aerial respiration at parturition (when breathing movements
are essential). Furthermore, FBMs are thought to be critically
important for the proper development and maturation of the
pulmonary circulation (348), as well as for normal growth
and differentiation of functional lung tissue [for a review,
see (227)].
FBMs induce mechanical forces within lung tissue via
cyclic stretch and strain, which in turn provide a suite of
local cellular signals, including paracrine release of sero-
tonin from pulmonary neuroendocrine cells and surfactant-
related release of membrane bound lipids (279, 336, 396).
When FBMs are absent, either in vitro or in vivo, potentially
fatal pulmonary hypoplasia can result (228, 229, 248, 277).
Pulmonary hypoplasia in this context seems to involve both
decreased cell proliferation (228-230,444) and increased pro-
grammed cell death (456). It is likely, therefore, that FBM
and the resultant mechanical forces are associated with spe-
cific molecular differentiation instructions; for example, in the
absence of FBMs, type I and type II pulmonary cells remain
immature and nonfunctional (229). FBMs seem to epitomize
both a form of early training for aerial respiration and an
1035
The Muscles of Breathing
important source of signaling for lung growth and maturation.
This is, of course, also true in adult motor systems in which
the demand for increased respiratory activity increases motor
unit activity acutely while also activating signaling pathways
that lead to growth and hypertrophy of skeletal muscles.
Despite the evident importance of FBMs for the devel-
opment of healthy lung tissue, the relationship between early
breathing-related rhythmicity and the normal development
of the neuromuscular system remains unclear and relatively
underexplored. It is important to note that the term FBMs
reflects the important role of aerial gas exchange in vertebrate
physiology. However, because FBMs are produced by many
muscles acting together, and, not unlike the adult respiratory
system, they involve muscles that underlie a range of orofa-
cial and respiratory behaviors. The nerves and muscles that
produce FBMs overlap with primordial versions of chewing,
suckling, and even neck movements. To review this topic, we
will necessarily focus on works from both in situ and in vivo
investigations in a variety of vertebrate species, and we will
describe data from human subjects when it is available. We
will also discuss the potential relationship between so-called
rhythmic spontaneous neural activity and FBMs proper [for a
review, see Momose-Sato and Sato (299)].
Information regarding the specific brainstem-derived
mechanism(s) of FBMs originates almost exclusively from
non-human mammalian and avian species as mechanistic and
reductionist studies of this sort are not possible in humans.
Spontaneous neural activity produces a variety of muscu-
lar movements in utero, but this wave of activity is generic
and anatomically and functionally undifferentiated. It is cur-
rently not clear how neural circuits that are widespread and
active during early embryonic development are transformed
into brainstem circuits that are terminally differentiated and
give rise to specific ventilatory and other motor behaviors,
although experimental animal models have the potential to
shed more light on this subject (178, 459).
At least as early as the late nineteenth century (141, 460),
there was interest in the development and maturation of
FBMs, but the lack of methods to observe and record this phe-
nomenon directly precluded controlled experimental research
on this topic. It was not until the late twentieth century and the
arrival of real-time 2D sonography, which allowed researchers
to observe previously concealed fetal activities that a common
focus on this area returned and theories about the origin of
FBMs began to be tested more rigorously (116). FBMs can
now be observed in the human fetus as early as the tenth
week of gestation, although the most commonly described
chronological age of onset of FBMs is around 12 weeks
(43, 117, 174, 247). FBMs begin as irregular and inconsistent
episodes of breathing-like muscle activity separated by long
pauses, that is, embryonic apnea. FBMs are first detected as
an enlargement of the abdominal region and a decrease is tho-
racic volume. This has been defined as paradoxical breathing,
compared to the more symmetrical expansion of the thorax
and abdomen in mature animals. Paradoxical breathing in
this context is likely due to the robust early influence of the
1036
Comprehensive Physiology
diaphragm moving caudally as it contracts, which draws the
sternum and thorax inward and pushes the abdomen outward,
and due to the high viscosity of fetal lung fluid compared to air
and the high compliance of the fetal and neonatal chest wall
(317, 365). The result of this muscle activation pattern is a
small decrease in intrathoracic pressure and small tidal move-
ments of viscous amniotic fluid within the trachea and lung.
The latter has been shown directly via scanning ultrasound,
diaphragmatic and laryngeal electromyography (EMG), and
tracheal pressure measurements in chronically instrumented
sheep in utero (97).
Activity cycles of breathing movements in human infants
and other mammals adjust in concert with gestational age, cir-
cadian oscillations, behavioral state, and maternal ingestion
of foodstuffs. Although brief and intermittent at first, FBMs
become more consistent and steady and appear more often
after approximately 20 weeks gestation (443). After about 33
to 34 weeks in utero, the rate of FBMs is about 40 breaths/min
and the overall incidence of FBMs continues to increase as
gestation progresses (253). However, FBMs going forward
tend to occur more often as episodic bouts of activity, happen-
ing in complex clusters separated by embryonic apneas, rather
than occurring singularly. FBMs are tightly correlated with
low-voltage high-frequency electrocorticograms (LV-ECoG)
(similar to the scenario during “active” or REM sleep), at least
in unanesthetized sheep in utero (46,371). FBMs occur rarely
during episodes of high voltage, low frequency electrocor-
ticogram activity (HV-ECoG). The presence of FBM during
LV-ECoG is further correlated with the inhibition of nuchal
EMG and spinal reflexes, which may reflect the growth and
maturation of caudally descending inputs cranial to the pon-
tine and medullary regions generating different behavioral
states and thereby influencing the breathing pattern. It is an
open question whether FBMs earlier in the developmental
process are associated with a behavioral state that resembles
the LV-ECoG state (which looks like the fetal equivalent of
rapid eye movement sleep) because sleep states are defined
phenomenologically based largely on the cortical EEG. Dur-
ing earlier stages of development, it may be that the fetus
lacks sufficient cortical development and tissue to generate
an EEG with enough complexity to allow ECoG scoring even
though the brainstem manifestations of different behavioral
states may be present. Alternatively, the brainstem behav-
iors associated with REM sleep may develop earlier than the
forebrain manifestations of REM sleep. The situation may be
analogous to the definition of REM sleep in the echidna, an
animal not originally thought to have REM sleep, but which
has been shown to have many of the brainstem manifestations
of REM sleep while simultaneously demonstrating relatively
high voltage cortical EEG activity (407). The relationship
between FBMs and behavioral state is further supported by
evidence derived from surgical separation of the pons and
medulla from the midbrain, which eliminates the relation-
ship between behavioral state and FBMs (42, 98). By the last
trimester in humans, FBMs are also altered by circadian oscil-
lations linked to elevated maternal melatonin secretion (292),
Volume 9, July 2019
Comprehensive Physiology
blood gases, and circulating maternal glucose concentrations
[for a review, see Koos and Rajaee (253)]. FBMs tend to
increase following a meal during the last 10 weeks of ges-
tation (195, 318). It is, therefore, no surprise that caffeine,
alcohol, nicotine, and many other pharmacological perturba-
tions influence FBMs. Unfortunately, the manner in which
these fetal perturbations affect the development of breathing
rhythm and pattern, both acutely and chronically, remains
a young, but critical area of investigation in which much
remains to be discovered.
As parturition nears, the occurrence and rate of FBMs
tend to fall or disappear altogether (37). This is perhaps
due to the continued development of supraspinal neural cir-
cuits that can actively engage inhibitory descending inputs to
breathing-related circuitry, but the simple advent of inhibitory
neurotransmission is likely an oversimplification of this phe-
nomenon. For example, while there is evidence that descend-
ing inputs tonically inhibit breathing circuits near the end of
gestation, other conditional influences also have been impli-
cated during this time. It is well known that hypoxia inhibits
FBMs (168,287,461) by purinergic (252) and/or opioid recep-
tor activation because blocking endogenous adenosine recep-
tors and opioid receptors seems to enhance breathing behav-
ior in newborn animals (205). There is also some evidence
that the extra-embryonic placental membranes that surround
the fetus may inhibit FBMs near birth. Several experimental
results point to the role of local prostaglandin biosynthesis
and the role of allopregnanolone as factors that may enhance
NREM sleep, sedate the fetus, and suppress FBM (10, 309).
It is a clever adaptation that allopregnanalone, which is an
inhibitory pregnane neurosteroid derived from the placenta
that binds to GABAA receptors and increases the channel open
time, ceases to be a factor when the fetus is born and sepa-
rated from the placenta. Thus, the respiratory inhibition from
allopregnanolone disappears at birth, and something similar
may happen with adenosine since the newborn exists in a rela-
tively well-oxygenated environment compared to the fetus. It
is, therefore, important that future studies address the mech-
anisms of the inhibition of FBMs more directly, especially in
the transition between the aquatic intrauterine environment
when FBMs are inhibited and the well-oxygenated, aerial
environment of the newborn where regular respiratory activ-
ity becomes essential.
An unresolved, and perhaps enigmatic, issue regarding
near-term inhibition of FBMs is how the developmental tim-
ing of inhibitory control of breathing matures when chloride
conductance is switching from excitatory (outward) in the
prenatal embryo to inhibitory (inward) near the transition to
aerial breathing (33). Understanding the nature and timing of
this switch may help explain the increased incidence of apnea
in preterm and near-term babies at parturition. Having said
that, the entire issue of the developmental shift in GABAergic
signaling from an excitatory to an inhibitory influence has
been questioned recently, since most of the evidence support-
ing a role for a developmental shift in chloride conductance
comes from reduced preparations, and several studies in intact
Volume 9, July 2019
The Muscles of Breathing
animals suggest that GABA has a consistently inhibitory
effect in neonatal animals. It is possible that the timing of
the shift in chloride conductance as a function of age may
be influenced by the isolated, in vitro, experimental prepa-
rations used to demonstrate it (52, 246, 445, 488) [also see
(34)]. Clearly, further work will be needed to understand what
role the well-documented switch from excitatory to inhibitory
GABAergic transmission plays in the development of FBMs
and neonatal respiratory patterns.
A final topic related to the theme of FBMs concerns the
relationships between rhythmic spontaneous neural activity
(rSNA) in vitro and whole animal FBMs that occur in utero,
and the development of functional breathing circuits during
the embryonic and fetal periods. rSNA is defined as a con-
sistent large-scale depolarization wave produced by a rela-
tively undifferentiated nervous system when isolated in vitro.
In some vertebrate species, rSNA propagates widely within
the CNS and can be measured from cranial nerves that will
carry future (i.e., functional) respiratory-related motor out-
flow. In the embryonic chicken (Gallus gallus) for example,
Fortin et al. (148) showed that rSNA measured via cranial
nerves V, VII, IX, X, and XII and spinal nerves C1-C5 all
exhibited similar synchronized waveforms of rhythmic activ-
ity between stages 24 and 36 (embryonic days 4-8). These data
suggest that early rhythmogenic neural circuits must undergo
considerable differentiation and specialization during gesta-
tion to produce functional, behavior-specific circuits at birth.
For example, studying synaptic activity during growth and
development can regulate programmed cell death in specific
motor pools (23). Moreover, while some authors treat early
electrical oscillations and FBMs as independent developmen-
tal phenomena, there is evidence that rSNA and FBMs are
related. It is likely that rSNA and FBMs reflect early spon-
taneous network output in vitro and in vivo, respectively, as
primordial biorhythms transform and mature into well-known
functional neural circuits for aerial breathing, such as the pre-
Bötzinger complex and/or the parafacial respiratory group
(437, 438). For example, FBMs in utero begin around the
same gestational age or immediately after the first sign of
rSNA in vitro, at least in species where both phenomena have
been measured (174, 250, 267, 268). However, the develop-
mental details of the earliest observed electrical oscillations
as they pertain to the normal and abnormal maturation of
breathing-related central pattern generators have received lim-
ited attention and are largely unknown (439,458); for reviews
with a genetic emphasis see (44, 79). This may stem from
the relatively late appearance of rSNA and FBMs in rodents
compared to humans. rSNA and FBA appear during the fetal
period at approximately embryonic day 14.5 in rats and at 13
days in mice or 75% and 65% of total gestation, respectively.
In humans FBMs are first detected between weeks 10 and 12
in utero (43, 191, 253), which is roughly 27% to 33% of total
gestation. These differences in the manifestation of breathing-
related rhythmogenesis undoubtedly reflect differences in the
species-specific, altricial-precocial spectrum when compared
to humans, and highlight the difficulty of directly comparing
1037
The Muscles of Breathing
developmental trajectories among different animal groups. A
newborn rat, for example, is relatively younger than a human
newborn. When the former is born, it is considered compara-
ble to a human at 24 to 26 weeks of gestation (94, 354).
The limited information about the early developmental
influences of rSNA on the respiratory system also reflects
the difficulty in studying embryonic circuit formation and/or
FBMs in placental mammals over the entirety of gesta-
tion, especially given the added complications of maternal
influences. Few experimental models can accommodate this
requirement, and therefore, the degree to which earlier spon-
taneous activity may determine proper breathing-related net-
work formation remains largely untested. This is in contrast
to information about the role of rSNA for the proper devel-
opment of spinal networks in which rSNA has been linked to
a number of maturational phenomena, including motoneuron
differentiation (481), axon pathfinding (190), neurotransmit-
ter phenotype (119), and the expression of ion channels (323).
In the context of the respiratory system, most current infor-
mation about the influence or rSNA has been descriptive.
For example, it is clear that the widespread rSNA become
restricted segmentally near the onset of pre-Bötzinger driven
inspiratory activity in rodents (335,439), when synaptic trans-
mission transforms from a largely cholinergic driven exci-
tation to one dominated by glutamate; a similar transition
occurs in spinal cord motor circuits (362). However, the
role of rSNA in producing a healthy and functional breath-
ing network is still in its infancy. One relevant study indi-
cates that the release of brain-derived neurotrophic factor
(BDNF) was activity-dependent in the isolated brainstem-
spinal cord preparation in that its concentration was propor-
tionally increased or decreased in concert with increases and
decreases of rhythmic cranial motor outflow in the rat fetus
(13). These data show that activity-dependent BDNF signal-
ing could support the development and maturation of synaptic
signaling in brainstem breathing circuits. In other experi-
ments, BDNF knockout animals exhibit slower respiratory-
related motor burst rates, punctuated by long pauses (apneas),
and considerable cycle-to-cycle variation (22, 241). Interest-
ingly, synaptic deficits due to BDNF loss of function in neu-
rons from other brain regions (i.e., not breathing-related neu-
ronal regions) can be reversed by exogenous BDNF (341).
This subject has also inspired continued work in a variety
of comparative model systems that provide tractable experi-
ments by which to study the organization and maturation of
breathing-related neural networks from their onset through
birth. In birds, for example, Vincen-Brown et al. (459) have
shown that primordial breathing-related hindbrain circuits can
be continuously monitored without interruption in an altricial
species from their inception to their functional maturation at
hatching. Figure 2 shows an example of circuit maturation
of breathing-related activity produced in vitro from the zebra
finch hindbrain preparation. Note that primordial breathing-
related activity via cranial motor axons commences on embry-
onic day 4 (i.e., rSNA) and continues through external pip-
ping or hatching on embryonic day 14 when continuous and
1038
Comprehensive Physiology
Embryonic day 4: onset of spontaneous activity
∫Cranial
nerve Xl
100 s
Embryonic day 7
100 s
Embryonic day 14: continuous breathing established
100 s
Figure 2 Example recordings of prenatal and perinatal breathing-
related neural activity from a developing zebra finch. Motor outflow is
shown as rectified and moving time averaged (time constant = 200 ms)
cranial nerve XI (spinal accessory) activity. Cranial nerve XI motor out-
flow is considered inspiratory as it innervates the cucullaris muscle in
birds, which is thought to be homologous to the sternocleidomastoid
and trapezius in humans. The top panel shows the first observable neu-
ral activity from cranial nerve XI at stage 22 or embryonic day 4 (E4)
(310). Cranial nerve activity at this age is considered to be a generic
large-scale depolarization wave that spreads throughout the neuraxis.
At this stage, most spinal and cranial nerves display synchronous dis-
charges and a similar waveform. The middle panel shows a transitional
period where the underlying chemical communication and morphologi-
cal connectivity in the developing breathing network is being modified,
although the mechanisms for these changes are unknown. The lower
panel shows a cranial nerve XI recording from a hatchling bird (i.e.,
internally and externally pipped through the eggshell). This breathing-
related motor outflow achieves a high frequency and is critically depen-
dent on AMPAergic neurotransmission (459).
functional breathing-related activity must be established. This
model provides an excellent opportunity to explore the funda-
mental basis for the onset and organization of neural wiring
for rhythmic motor behaviors using a specific behavioral con-
struct both in vitro and in vivo. The avian embryo can be
accessed at any time during embryonic development without
the confounding influences of a maternal host. Avian species
also provide a developmental timeline that may be useful for
comparison to mammals, including humans, although some
rhythmic motor behaviors that employ respiratory muscles in
mammals (e.g., suckling) do not have comparable behaviors
in birds. Nevertheless, rSNA via cranial motor outflow and
associated spontaneous movements in birds, which are likely
precursors of rhythmic respiratory motor activity, first appear
near embryonic day 4, corresponding to 19% of total gesta-
tion in chicks (Gallus gallus) and 28% of gestation in zebra
finch (Taeniopygia gutatta). Assuming that early rSNA is a
precursor to FBMs, this temporal switch occurs much earlier
in birds and humans than in rodents.
Volume 9, July 2019
Comprehensive Physiology The Muscles of Breathing

Functional neural innervation, and
respiration-related output of the muscles of
breathing
In humans, all breathing muscles are part of the cranial and
postcranial axial skeleton, though this is not true in all mam-
mals. In this section, we review all muscles with a documented
role in breathing, with the muscles grouped as follows: nose,
head and neck, tongue, soft palate, suprahyoid, infrahyoid,
pharyngeal, and laryngeal muscles—often described as acces-
sory and/or upper airway muscles; muscles of the thorax and
abdomen—often described as pump muscles; and muscles of
the back, which may lack regular respiratory-related activ-
ity, but can be recruited when respiratory drive is increased
(Table 1). In the following section, we consider the attach-
ments, mechanical action, neural innervation, and respiration-
related discharge pattern of each muscle. We also point out
if the muscles are active in quiet breathing (eupnea), or only
under conditions of increased respiratory drive. The final com-
mon output of the respiratory motoneurons supplying a par-
ticular muscle is most commonly evaluated by recording the
electromyogram (EMG) or the efferent muscle nerve activity.
It should be noted that an increase in neural drive to a muscle
changes both the discharge rate of active motoneurons (rate
coding) as well as recruitment of motoneurons that were inac-
tive before neural drive changed. Thus, increased amplitude
of muscle EMG activity or motor nerve output reflects the
interplay of these underlying changes in neural activity. We
have chosen to confine the discussion to humans, though if
respiration-related activity of a given muscle has not been
recorded in humans, we have used information from lower
mammals.
Nasal muscles
The external nose is invested with several small muscles,
including the procerus, levator labii superioris alequae nasi,
transverse nasalis, alar nasalis, dilator naris, apices nasi, and
depressor septi (Table 1 and Fig. 3). The nomenclature of
these small muscles varies somewhat from source to source.
The muscles are unique in that they originate on bone or carti-
lage, and insert into cartilage, skin or connective tissue on the

(A) (B)

I 1 sec
1 Procerus (1) 1

Levator labii 2
superioris
alaeque nasi (2) 2
Nasallis (transverse) (3) 3

3 4

6
6
5
Apicis nasi (6)
4
7 (C) Quiet nasal breathing
60 Nasal breathing after exercise
Dilator naris (5)
Nasalis (alar) (4)
Depressor septi (7)
EMG (% max)

40

20

0
su rus

ris

e)

r)

Ap aris

si
la

na
as ers
rio
e

(a

rn
oc

is
pe

sv

is

to

ic
Pr

an

al

ila
(tr

D
i
bi

N
is
La

al
r

as
to

N
va
Le

Figure 3 Muscles of the external nose. (A) The numbers on the muscles in the schematic correspond to the like-numbered EMG recordings
shown in in Panel B. The EMG recordings were obtained during voluntary nasal flaring. Panel C shows nasal muscle activity during quiet
nasal breathing and immediately after exercise (“20 deep knee bends”), at which time subjects were instructed to breathe through the
nose. EMG activities are expressed as a percentage of maximal activity, which was evoked by a maximal voluntary “grimace.” All figures
adapted, with permission, from (60).

Volume 9, July 2019 1039

The Muscles of Breathing
external nose, and/or to adjacent nasal muscles (Table 1 and
Fig. 3) (180). However, the origins and insertions of the mus-
cles appear to vary widely, and the literature is filled with
conflicting descriptions, which may reflect intersubject vari-
ability. Nonetheless, there is consensus that the zygomatic
branch of the facial nerve innervates all the nasal muscles,
with the motoneuron cell bodies in the facial motor nucleus.
The muscles are grouped functionally as elevators (shorten
the nose while dilating the nostrils), depressors (lengthen
and dilate), compressors (lengthen and narrow), and dilators
(dilate the external nares). Because the fibers are just beneath,
or a part of, the skin, EMG activity of these muscles is easily
recorded with surface electrodes, though the muscles are so
small that it is difficult to record from only a single nasal
muscle. Nonetheless, many studies of the respiration-related
activity of the nasal dilator group have been done, starting with
Hering and Breuer in the nineteenth century, who used nasal
muscle electrical activity as an index of inspiratory motor
output during their descriptions of the Hering-Breuer reflex
(54, 203), which was confirmed much later (426).
With the exception of the depressor septi, all nasal mus-
cles assist in widening the nasal opening, especially during
labored breathing evoked by increased nasal airflow resis-
tance, hypoxia or hypercapnia (51, 55, 56, 60, 69, 70, 87, 92,
152, 185, 278, 293, 403, 426, 428, 433, 452, 454, 468, 475). The
location and orientation of the nasal muscles are shown in
Figure 3, Panel A, and panel B shows representative EMG
recordings from each of the nasal dilator muscles, which are
identified by the corresponding numbers in Panel A. The activ-
ity is expressed as a percentage of the maximal activity evoked
by volitional flaring of the nostrils. As shown in Panel C, activ-
ity of these muscles during eupnea is minimal, but becomes
substantial immediately after a brief bout of exercise, and the
greatest increase in activity is recorded in the dilator naris
and apices nasi. The valving function of the nasal dilators
significantly reduces nasal resistance and dictates, in part,
the distribution of breathing between the nose and the mouth
during exercise (152, 449).
Muscles of the head, and head and neck
Muscles in this group in which we found examples of
respiration-related activity include the masseter, trapezius,
sternocleidomastoid, scalenes, and the medial and lateral
pterygoid muscles. The only muscles reported to be active
during eupnea is the scalene muscle group (Table 1 and Fig. 4).
The masseter muscle consists of a superficial and a deep
head, (Fig. 4A and Table 1), with both heads innervated by the
mandibular division of the trigeminal nerve. When the mas-
seter contracts, the mandible is elevated, though mandibular
protrusion can occur as well and this would widen the upper
(oral) airway. Perhaps this explains the respiration-related
discharge that occurs under conditions of very high respi-
ratory drive. The recordings in Figure 4A show that breathing
against a very high inspiratory resistance evoked inspiratory
activity of the masseter muscle, in phase with the activity
1040
Comprehensive Physiology
recorded from the dilator naris (211). Thus, the masseter can
assist inspiration by lowering upper airway resistance when
the resistance to airflow is very high.
The trapezius muscle (Table 1 and Fig. 4B) has three func-
tional regions, with respiratory-related activity present mainly
in the upper trapezius muscle, which receives its motor supply
from the spinal accessory nerve (cranial nerve 11). Although
the muscle’s main function is moving and/or stabilizing the
scapula, it can rotate the clavicle and possibly elevate it, which
could augment inspiration; indeed, breathing-related activity
has been recorded during voluntary deep breathing maneuvers
(see the following text). However, even when the scapula is
fixed, trapezius muscle contraction can move the spine, which
could influence rib cage dimensions and affect respiration,
though the biomechanics of this have not been worked out.
There have been relatively few attempts to record
respiration-related activity of the upper trapezius muscle, and
the majority of studies suggest that the activity is largely
tonic in quiet breathing. For example, tonic upper trapezius
muscle activity has been observed in decerebrate cats (4), in
nasal and mouth breathing adults (441), and in 1-week-old
human infants (391). However, in mouth breathing children
(10-11 years old), some phasic, respiration-related activity
was noted during quiet breathing, but trapezius activity was
reduced following a therapy program that targeted improved
diaphragmatic breathing (89), consistent with an accessory
role that can support gas exchange when the diaphragm is
not functioning optimally. In support of this, trapezius mus-
cle activity can be evoked by vigorous, volitional inspiratory
efforts (Fig. 4B) (93) or when performing maximal inspi-
ratory efforts against an occluded airway, with the latter
study showing a significant correlation between EMG activ-
ity and maximal inspiratory pressure (i.e., effort). This was
true in both intact subjects and those with spinal cord injury
(435). Although these maneuvers evoke peak muscle acti-
vation under isometric conditions, they provide important
insight into the potential contribution of the muscle to rib cage
expansion. On the other hand, the upper trapezius was inac-
tive during normal speaking, but showed expiratory activity
during singing tasks that included prolonged periods of expi-
ratory airflow (343, 344), with the activity in phase with that
recorded in the internal intercostal and abdominal muscles.
Based on these findings, the upper trapezius contributes to
compression of the upper thorax during singing (and likely
other prolonged and forceful expiratory maneuvers), thereby
serving an expiratory function. There appears to be an impor-
tant task-dependent role for the upper trapezius muscles, such
that they can either expand or compress the rib cage, though it
is clear that we know little about the breathing-related function
of these muscles. Given that the motoneurons of the muscles
are in the brainstem, the trapezius may be an important focus
of rehabilitation in patients with high spinal cord injuries.
The sternocleidomastoid muscle (“sternomastoid”) is a
superficial neck muscle, though it is much thicker than the
scalenes, is easily observed in human subjects, and is thus
amenable to study with EMG electrodes (Fig. 4B and Table 1).
Volume 9, July 2019
Comprehensive Physiology The Muscles of Breathing

(A) (B)
SCM motor units
0
Pressure
Trapezius A (cmH2O)
40
B
Mass Sternocl 2 Inspiratory
eter eidomastoid 0 flow (L/s)
1s
Masseter
EMG Trapezius
Alae nasi EMG
EMG

Pharyngeal Chest wall

pressure motion
(cmH2O) –50
5s
(D)
Anterior
(C) Lateral pterygoid, superior head scalene Middle
scalene
Lateral pterygoid, inferior head
Posterior
scalene
Medial pterygoid, deep head
Medial pterygoid, superficial head
Unit
Tensor palatini Average
Medial pterygoid EMG
Firing
Nasal pressure rate
Chest wall
motion

Figure 4 Muscles of the head and neck. Panel A shows the location of the human masseter muscle and masseter EMG activity
recorded in a human subject breathing against a large inspiratory resistance (see pharyngeal pressure trace). The dilator muscles of
the nose were recorded simultaneously. Adapted, with permission, from (211). Panel B shows the locations of the sternocleidomastoid
(SCM) and trapezius muscles, motor unit recordings from the SCM, and superimposed recordings of airway opening pressure and
airflow (6). Trapezius muscle EMG recording and associated chest wall motion (inspiration up) are displayed from a healthy human
subject who was asked to take deep breaths, from Daimon and Yamaguchi (93). Panel C is a schematic drawing of the lateral and
medial pterygoid muscles. The associated recordings show EMG activity of the medial pterygoid in an awake human subject instructed
to take deep inspirations; note the marked recruitment during inspiration, from Sauerland et al. (389). Panel D shows the location of
the anterior, middle, and posterior scalene muscles and recordings of motor unit discharge during tidal breathing in a healthy male
subject. Which of the three scalene muscles used for this recording was not indicated, but we presume the anterior head. Tracings
show (from top to bottom): raw and integrated EMG, instantaneous motor unit firing rate, and chest wall motion (inspiration up). The
inset to the right of the motor unit recording shows overlaid motor unit potentials from one of the identified motor units. Adapted, with
permission, from Saboisky et al. (379).

The sternocleidomastoid is innervated by the spinal accessory
nerve, so although high cervical spinal cord injuries result in
denervation of the diaphragm, intercostals and scalenes, the
sternocleidomastoid innervation remains intact, which makes
the sternocleidomastoid muscle, like the trapezius, a target for
training and respiratory rehabilitation in patients with cervical
spinal cord injury. Although the primary action of the mus-
cle, when activated unilaterally, is contralateral head rotation
and neck flexion, simultaneous contraction of both sternoclei-
domastoid muscles elevates the clavicle, consistent with an
accessory inspiratory function. Although the scalenes have
a much greater mechanical action on the rib cage than the
sternocleidomastoid, the increased mass of the latter suggests
that maximal activation of the two muscles would result in
the same change in thoracic volume (273).
The breathing-related action of the sternocleidomastoid
has not been studied as extensively as the scalenes, and
the studies that have been done suggest that there is little
breathing-related activation until inspiratory drive is very high
or when the action of other rib cage muscles is absent after
denervation. Adams et al. (6) showed that the sternomas-
toid EMG was silent during eupnea in both control sub-
jects and those with COPD, consistent with observations in
supine, anesthetized dogs (103, 107). As shown in Figure 4B
(“SCM motor units”), the muscle was recruited when subjects
breathed against an imposed resistance to inspiratory airflow
(6, 53) and by intense volitional inspiratory efforts, though
the level of recruitment of the sternocleidomastoid was often
less than that in the diaphragm and external intercostal mus-
cles when recorded during the same maneuvers (161, 311).

Volume 9, July 2019 1041

The Muscles of Breathing
Similarly, sternomastoid activity was only recorded in three
of seven subjects who were asked to perform a vigorous nasal
sniff, which caused intense activation of the diaphragm in all
subjects (240). In anesthetized rabbits, progressive asphyxia
failed to recruit the sternomastoid, though recruitment was
evoked when animals began gasping (284). Interestingly, 8
of 11 patients who failed to wean from mechanical ventila-
tion showed sternomastoid activity, compared to only 1 of 8
patients who successfully weaned (338), suggesting that the
sternomastoid was compensating, ineffectively, for a weak-
ened diaphragm in the former group of patients.
Scalene muscles. There are three pairs of scalene muscles,
referred to as anterior, middle and posterior scalenes (Fig. 4D
and Table 1). The scalenes are innervated by the fourth, fifth,
and sixth cervical spinal nerves (C4-C6). Contraction of the
muscles elevates the first and second ribs, contributing to
rib cage expansion along the anterior-posterior axis, as well
as the rostral-caudal axis. Campbell (67) reported that eup-
neic inspiratory activity in the scalenes was present in some
supine subjects, and most subjects demonstrated respiratory-
related activity when asked to take large volitional inspiratory
efforts. In some subjects, the scalenes were also recruited dur-
ing intense expiratory efforts, suggesting that they may play
a role in expulsive maneuvers such as coughing. Saboisky
et al. (379) found that discharge of scalene muscle motor
units was largely confined to the inspiratory phase of the
breathing cycle, although a few units showed tonic or phase
spanning activity (Fig. 4D). Interestingly, the motor unit dis-
charge rate increased by only 2 to 3 Hz from the beginning
to the end of inspiration, suggesting that drive to the muscle
may depend more on recruitment of additional motor units
rather than modulation of the firing rate of motor units that
are already active. This is consistent with earlier work from
the same group (159) showing that increased respiratory drive
evoked by dead space breathing was associated with increased
motor unit recruitment. Druz and Sharp (129) showed that
scalene activity was greater in the upright than the supine
posture, suggesting an increased contribution from rib cage
expansion to the tidal volume when standing. Chiti et al. (83)
showed that the scalene EMG increased as a function of respi-
ratory drive and that the activity correlated with the severity of
dyspnea. Fournier et al. (149) studied anesthetized hamsters
and showed that scalene activity was absent during eupnea,
but increased consistently during hypercapnia, following ipsi-
lateral denervation of the phrenic nerve, and in response to
an imposed resistance to inspiratory flow (“resistive breath-
ing”). The activity was always in phase with diaphragmatic
activity. These results suggest that the scalenes are accessory
inspiratory muscles in this species. In contrast, eupneic sca-
lene activity was not observed in lightly anesthetized, supine
baboons (107) or dogs (103); in the latter study, only four of
nine dogs had scalene activity during hypercapnia. Legrand
et al. (272) studied anesthetized rabbits and found variable
activity across animals, and when present, it was recorded in
the medial but not the lateral scalene. These findings in non-
human, animal models suggest that posture and/or anesthesia
1042
Comprehensive Physiology
may mask scalene activity, which is clearly observed during
quiet breathing in human subjects, especially when upright.
However, Warner et al. (464) showed that 6/6 supine sub-
jects had phasic inspiratory activity in the scalenes while
under halothane anesthesia, while only 4/6 subjects had sca-
lene activity before anesthesia. By the same token, posture
and increased respiratory drive can enhance activation of the
sternocleidomastoid and scalene muscles. These accessory
muscles play a significant role in augmenting respiration in
patients with chronic obstructive pulmonary disease in whom
the diaphragm is flattened and at a mechanical disadvantage.
Both sternocleidomastoid and scalene muscles tend to lift the
clavicle and the first two ribs and augment expansion of the
chest, especially when the shoulder girdle is fixed by resting
the arms on a firm surface to increase the mechanical advan-
tage of these muscles (24). One can take advantage of this
posture to provide some relief to COPD patients with severe
dyspnea.
Pterygoid muscles. There are two pterygoid muscles, the
medial and lateral pterygoids, and both muscles are composed
of a superior and an inferior head—two sites of origin that
merge to form the body of the muscle (Fig. 4C and Table 1).
Both heads of the medial pterygoid assist the masseter in
mandibular elevation. The muscle is innervated by an offshoot
of the main trunk of the mandibular branch of the trigeminal
nerve; interestingly, this is the same branch that innervates the
tensor veli palatini muscle. The lateral pterygoid muscles are
innervated by the lateral pterygoid nerve, which is a subdi-
vision of the mandibular branch of the trigeminal nerve. The
main function of the lateral pterygoid is mandibular protru-
sion, though it also participates in mandibular depression and
thus mouth opening. We were able to find only two exam-
ples of respiration-related activity in the pterygoid muscles.
Yoshida (486) recorded EMG activity of the lateral ptery-
goid in a sleeping subject and showed a small recruitment of
the muscles a few seconds following a roughly 15 sec apnea.
The activity in the lateral pterygoid was temporally linked
with activity in the genioglossus muscle, though there was
more activity in the latter. In another study, Sauerland et al.
(389) recorded large bursts of EMG activity in the medial
pterygoid in an awake human subject instructed to take deep
inspirations, with the discharge of the muscle in phase with
that recorded from the simultaneously recorded tensor palatini
muscle (Fig. 4C).
Before leaving the topic of head and neck muscles, it
is noteworthy that we were unable to find studies of the
breathing-related activity of the levator scapulae muscle. We
say this for two reasons: first, as the name suggests, con-
traction of the muscle elevates the scapula (and can also
cause slight rotation of the scapula), which could lengthen
and thus expand the thorax; and second, the levator scapulae
motoneurons are in the C3 to C5 regions of the spinal cord,
in close apposition to the phrenic motoneurons. In this con-
text, a detailed exploration of respiration-related activity of
this muscle is warranted, especially during maximal inspira-
tory efforts when other axial and thoracic muscles lengthen
Volume 9, July 2019
Comprehensive Physiology
the thorax and arch the back to augment expansion of the
thorax.
Tongue muscles. The tongue is composed of muscle fibers
and connective tissue. The tongue has only one fixed inser-
tion on the midline of the backside of the lower jaw, and it
functions as a muscular hydrostat; in this, tongues resemble
octopus tentacles and elephant trunks (245). Hydrostats are
incompressible and as such can elongate, shorten and stiffen
without changing volume. For example, tongue protrusion is
associated with elongation of the tongue along its anterior-
posterior axis, and this change in shape is offset by complex
changes along the medial-lateral axis. Thus, since tongue vol-
ume does not change, the utility of tongue muscle contraction
in influencing upper airway patency is a function of tongue
size, position, shape, and stiffness. An important consequence
of this in the context of breathing is that a high ratio of tongue
volume to pharyngeal volume would result in a relatively
compromised airway.
In humans, there are eight tongue muscles. Four of these
are extrinsic muscles, which originate on bony structures
or connective tissue and insert into the tongue body (the
genioglossus, hyoglossus, styloglossus, and palatoglossus),
and four are intrinsic muscles (inferior longitudinalis, supe-
rior longitudinalis, transversus, and verticalis) in which the
fibers are wholly contained within the body or blade of the
tongue (17, 151, 410), though there is evidence that some
intrinsic fibers attach to the hyoid bone (158, 165). Most of
the tongue muscles that have been studied show respiration-
related activity, as described in a recent review (153). In the
following text, we consider the anatomy, innervation, and
mechanical action of each of the tongue muscles, and describe
each muscle’s respiration-related activity, when known. The
origins and insertions of the extrinsic muscles are given in
Table 1. Origins and insertions of the intrinsic muscles will
be described briefly in the text, as even the basic anatomic
features of these small muscles are poorly understood.
In terms of respiration-related activity, the genioglossus
is far and away the most extensively studied tongue mus-
cle, in part because its location allows needle electrodes to
be placed through the floor of the mouth (387) (see Fig. 5A
and B, and Table 1). The medial branch of the hypoglos-
sal nerve innervates the muscle. When both right and left
genioglossus fibers are coactivated, the tongue protrudes and
its more posterior regions are depressed, thereby stiffening
and dilating the pharynx. Contraction of the fibers on only
one side causes deviation toward the opposite side. This is
easily demonstrated by stimulating the medial branch of the
hypoglossal nerve unilaterally. Though typically not active
at rest in healthy subjects, increasing respiratory drive with
hypercapnia, hypoxia, or exercise recruits the genioglossus
muscle in nearly all species studied [for review, see (153)].
Once recruited, the muscle is active during the inspiratory
phase of the breathing cycle, though there is typically a
background of tonic activity upon which the inspiratory activ-
ity is superimposed. An example of genioglossus muscle
activity recorded in an awake human subject is shown in the
Volume 9, July 2019
The Muscles of Breathing
second and third traces of Figure 5E (288). Note the absence
of activity under baseline (eupneic) conditions, but substan-
tial inspiration-related recruitment throughout a 4-min period
of combined hypercapnia and hypoxia. It is important to bear
in mind that the activity evoked even with very high respi-
ratory drive is but a small fraction of the muscle’s maximal
potential activity, which in this case was taken as the EMG
activity obtained during a voluntary maximal tongue protru-
sion maneuver (recordings on the far right of each trace in
Fig. 5E).
The lateral branches of the hypoglossal nerve innervate
the hyoglossus muscle. The almost horizontal orientation
of the hyoglossal fibers explains its ability to retract and
depress the tongue, acting as an antagonist to the genioglossus
muscle (Fig. 5A and Table 1). The hyoglossus is recruited as
respiratory drive increases, and in animal models, the magni-
tude and time course of the recruitment parallels that observed
in the genioglossus (reviewed in (153), presumably to depress
and stiffen the tongue. This combined action appears to greatly
reduce the propensity for pharyngeal collapse (156). The
hyoglossus muscle is clearly recruited during combined
hypercapnia and hypoxia, as shown in Figure 5E (fourth and
fifth traces) (288). Indeed, the drive to the hyoglossus appears
to exceed that to the genioglossus when expressed as a per-
centage of the maximum activity. One caveat, however, is
that the electrode placement in this study was such that the
recorded activity was likely a combination of hyoglossus and
styloglossus muscle fibers, and isolated activity of the sty-
loglossus in human subjects has not been recorded.
As can be discerned in Figure 5A, many of the styloglossus
muscle fibers enter the tongue blade at about the same location
as fibers from the ipsilateral hyoglossus muscle, while other
fibers insert into the inferior longitudinalis muscle (Table 1).
Thus, recording styloglossus activity in isolation is very diffi-
cult, as the electrodes need to be placed as close to the styloid
process as possible to avoid contamination from the hyoglos-
sus. The lateral branch of the hypoglossal nerve innervates
the styloglossus, and its action is elevation of the sides of
the tongue, as well as tongue retraction. The combination of
lateral tongue elevation, which creates both retraction and a
trough in the tongue surface, underscore the muscle’s primary
role in swallowing.
Although we were unable to find any studies reporting
respiration-related activity of the styloglossus in human sub-
jects, this has been examined in the anesthetized dog (483).
As shown in the upper tracing of Figure 5F (483), there was
no respiration-related styloglossus activity observed under
baseline conditions (left hand panels), but intense recruitment
occurred 10 to 15 s after injection of a 0.5% NaCN solu-
tion close to the carotid body (middle and right-hand panels),
demonstrating that stimulation of peripheral chemoreceptors
evoked a reflex increase in drive to the styloglossus. These
observations support the concept that all tongue muscles are
typically activated in all (or certainly most) tongue move-
ments (245). It is clear that the role of the styloglossus in
breathing warrants further investigation.
1043
The Muscles of Breathing Comprehensive Physiology

(A) (B)
SL IL T/V

GG SG HG

(D)

(C)
Verticalis

Transversus

Figure 5 Muscles of the tongue. Panel A contains schematic diagrams of the human tongue muscles from an impressive
anatomic evaluation by Sanders and Mu (383). In brief, the authors used images from the Visible Human Project to create
three-dimensional reconstructions, and also used various sagittal images to provide a detailed description of the muscles
of the human tongue. The upper row shows the intrinsic muscles superior longitudinalis (SL), inferior ongitudinalis (IL), and
the transversus and verticalis (T/V) muscles, whose fibers are tightly intermingled (see text). The bottom row shows the
extrinsic muscles genioglossus (GG), styloglossus (SG), and hyoglossus (HG). In each diagram, the indicated muscle or
muscles is darker than the whole tongue (gray). Two important features emphasized by the authors that have significant
bearing on the interpretation of tongue muscle EMG recordings include: (i) the superior longitudinal (SL) muscle is the only
unpaired muscle, and it also spans the length of the entire tongue; (ii) although the muscles are presented as separate
structures, the fibers of individual muscles intermingle extensively with those from adjacent muscles. A particularly important
example is that the genioglossus (GG) becomes the verticalis (V), and see blue highlighted region in Panel C) muscle in
approximately the middle third of the tongue. Panel B is a midline saggital image of a human tongue, highlighting the
superior longitudinalis (SL), the transversus/verticalis bundle (TV), the geniohyoid (GH), and two bellies of the genioglossus,
including the oblique GG (oGG) and the horizontal GG belly (hGG). Note that the fiber bundles of the hGG are longer
than those of the oGG (white lines) that the fiber density of all muscles is greatest anteriorally and is reduced at the tongue
base. It is clear that the human tongue has considerable curvature, as opposed to much more linear tongues in most lower
mammals, especially rodents. Panel C shows extrinsic and intrinsic fibers of the human tongue using in vivo imaging with
tractography, and nicely highlights the unique fiber orientation of the verticalis (blue) (158). The transversus muscle is not
easily seen in sagittal section, so we have included a transverse section that nicely delineates the muscle (158). Panel D
shows the human palatoglossus muscle (yellow arrow), which can also be seen in Panel C (orange fibers). The red and blue
arrows in panel D identify the soft palate and hard palate, respectively. Adapted, with permission, from (257). Panel E is a
representative record of genioglossus (“protrudor”) and hyoglossus (“retractor”) EMG recordings during 4 min of combined
hypercapnia and hypoxia in a healthy human subject (288). Note that for both muscles the unprocessed EMG and the
rectified and integrated EMG (iEMG) are shown. The upper tracing is expired airflow, and close examination shows that
the tongue muscles discharge during inspiration. Panel F shows EMG recordings of genioglossus (GG) and styloglossus
(SG) muscles in response to peripheral chemoreceptor stimulation with close arterial injection of NaCN in an anesthetized
dog (483). (G) Recordings from human palatoglossal muscle moving time-averaged EMG (top trace) and inspiratory flow
(433). (H) The tracings represent intrinsic superior longitudinalis EMG activity and esophageal pressure (Pes) in a supine,
urethane-anesthetized rat (20). The left-hand traces were obtained during quiet breathing and those on the right during
hypercapnia. Clear inspiration-related discharge can be seen in both instances. Thus, inspiration-related activity has been
observed in every mammalian tongue muscle that has been studied. See text for detailed discussion.

1044 Volume 9, July 2019

Comprehensive Physiology The Muscles of Breathing

(E)
Maximum (G)
Baseline Min 1 Min 2 Min 3 Min 4 Recovery
response
Expiratory
flow

PALATOGLOSSUS MTA EMG

Protrudor
EMG

Protrudor INSPIRATORY FLOW L/sec

iEMG

Retractor
EMG

Retractor
iEMG

(F) (H)
SG EMG
Intrinsic 0.025
0.000
EMG –0.025

Pes 0
GG EMG (cmH2O)
–20

30
Flow (L/min) 0
–30

P 0

(cmH2O) –40

Figure 5 (Continued )

The narrow, ribbon-like palatoglossus muscle originates
on the palatine aponeurosis of the soft palate, where it meets
the contralateral palatoglossal muscle (Fig. 5C & D). These
muscles define the palatoglossall arch, which is the border
between the oral cavity and the pharynx. From the arch, the
muscles descend and insert into the side of the tongue; super-
ficial fibers lie on the dorsal surface of the tongue, while
others enter the tongue and extend all the way to the intrin-
sic transversus muscle (discussed below). The palatoglossus
is the only tongue muscle not innervated by the hypoglossal
nerve. The source of palatoglossal innervation remains some-
what unsettled and is likely species-dependent; although the
consensus is that innervation is via the vagus nerve, there are
some reports that innervation is derived from the spinal acces-
sory nerve or the glossopharyngeal nerve. The main action of
the palatoglossus is elevation of the posterior portions of the
tongue and lowering of the soft palate, thereby closing the
oral opening to the pharynx. The palatoglossus is active dur-
ing swallowing onset, and there are some examples of a role
in breathing. For example, the upper recording in Figure 5G
shows an example of inspiratory-related palatoglossal activ-
ity in an awake, supine, male subject (433). The breathing-
related mechanical consequences of palatoglossal contraction
are poorly understood, but it likely plays a role in controlling
the proportion of airflow going through the nose and mouth
(“upper airway flow partitioning”).
The fibers of the intrinsic tongue muscles are mostly con-
tained within the tongue body, though their exact origins and
insertions have not been unambiguously defined. As a result,
we did not include these data in Table 1, and instead briefly
describe the complex fiber orientations of each of the intrinsic
tongue muscles. All information is based on the meticulous
dissections of the human tongue by Abd-El-Malek in 1939
(1) and more recently by Sanders and Mu (383).
The role of the intrinsic tongue muscles is to shape and
stiffen, rather than move, the tongue. As a result of the sig-
nificant intermingling of fibers of all intrinsic muscles and
their complex actions, the role of these muscles in breathing
has been largely ignored until recently. The easiest intrinsic
muscle to record from is the superior longitudinalis (Fig. 5A
and B), as it is easily accessible from the tip of the tongue.
The muscle fibers lie just beneath the mucous membrane of
the tongue and extend longitudinally from submucosal fibrous
tissue adjacent to the epiglottis all the way to the tongue tip.
Although most of the fibers are arranged along the long axis
of the tongue, some are obliquely oriented. When the fibers

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The Muscles of Breathing
contract, the body of the tongue shortens and thickens, thereby
contributing both to tongue retraction and dorsiflexion of the
tongue tip. As with all tongue muscles with a role in tongue
retraction, the lateral branch of the hypoglossal nerves inner-
vates the superior longitudinalis. A series of studies by Bailey
and colleagues demonstrated respiration-related superior lon-
gitudinalis activity in anesthetized, tracheotomized rats (15).
As shown in Figure 5H, there is inspiratory-related activity of
the superior longitudinalis (labeled “Intrinsic EMG”) under
baseline conditions (left panels), as demonstrated by burst-
ing in phase with negative swings in esophageal pressure
(Pes). The right-hand panels show substantial recruitment of
the muscle during hypoxia. Further experiments using careful
denervation of extrinsic retractor muscles combined with MRI
showed that stimulation of the hypoglossal nerves increased
velopharyngeal airway volume (19). When stimulation was
repeated after selective denervation of the nerve branches
supplying the intrinsic retractor muscles of the tongue, the
increase in velopharyngeal airway volume was significantly
reduced, indicating that the intrinsic tongue muscles con-
tribute to pharyngeal airway stiffening and/or dilation, and
thus play a role in the control of airflow resistance.
To the best of our knowledge, studies of respiration-
related activity of the other three intrinsic tongue muscles
has not been attempted. Nonetheless, we will briefly review
the anatomy and putative mechanical actions of each mus-
cle so that hypotheses regarding their role in the control of
pharyngeal airflow resistance can be constructed. The inferior
longitudinalis lies on the under surface of the tongue between
the genioglossus and hyoglossus muscles. Its fibers extend
from the base to the tip of the tongue, and some reports sug-
gest that at least some of the fibers originate on the hyoid bone;
if correct, this would be an exception to the concept that all
“intrinsic fibers” are wholly contained within the blade of the
tongue. Careful examination of Figure 5A suggests that the
fibers of this muscle likely intermingle with fibers of the sty-
loglossus, verticalis, genioglossus and hyoglossus. The close
proximity of these muscles increases the odds of mixed, con-
taminated, EMG activity. Nonetheless, the inferior longitudi-
nalis is likely a strong candidate for EMG recordings, as it
is reasonably accessible in most mammals, though humans
are a notable exception as the fibers are difficult to discern in
transverse sections of the human tongue (383). Importantly,
the potential for contamination from adjacent fibers could be
problematic even in lower mammals.
The verticalis muscle (Fig. 5B, labeled “TV,” and depicted
in blue in Fig. 5D), originates just beneath the superior
longitudinalis, and its fibers descend vertically where they
intermingle with the transversus and inferior longitudinalis
muscles. Contraction of the muscle appears to narrow the
tongue mediolaterally, while also elongating it. The medial
branch of the hypoglossal nerve innervates the muscle.
Finally, the transversus muscle (seen in sagittal section in
Fig. 5B and in cross section in the right-hand panel of Fig. 5D)
originates on the fibrous septum of the tongue midline, and
1046
Comprehensive Physiology
its fibers extend laterally from the midline to the sides of the
tongue where they intermingle with the fibers of the other
muscles, including the genioglossus. The medial branch of
the hypoglossal nerve innervates the transversus, and when
the fibers contract, they narrow and elongate the tongue and
contribute to tongue protrusion.
Muscles of the soft palate. This group includes the tensor
veli palatini, levator veli palatini and the musculus uvulae,
which is sometimes called the palatinus (Fig. 6A). We have
chosen to define the palatopharyngeus as a pharyngeal muscle
as its main action is on the pharynx (see below). The tensor
veli palatini lies slightly anterior and lateral to the levator veli
palatini muscle. The points of origin and insertion of its fibers
are given in Table 1. The muscle is innervated by the medial
pterygoid nerve, which is a small branch of the mandibular
division of the trigeminal nerve. As the name implies, the
muscle tenses the palate, allowing the levator veli palatini
to more easily elevate the palate. The main role of palatal
elevation is in swallowing, as elevation and stiffening of the
palatal walls prevents food from entering the nasopharynx.
However, the muscle is also active in breathing. Activation of
the tensor veli palatini likely plays a role in the switch from
nasal to oronasal breathing and likely dilates and stiffens the
retropalatal airway. Figure 6B shows phasic discharge of the
tensor veli palatini in an anesthetized dog (448). The activ-
ity is in phase with diaphragm activity, thus defining it as
an inspiratory muscle. Importantly, the activity of the tensor
veli palatini varied as a function of the breathing route: when
the breathing route was switched from tracheotomy breathing
(TB, low resistance; horizontal arrows below recordings in
Fig. 6B) to nasal breathing (NB, increased resistance), sig-
nificant recruitment of both tonic and phasic activity of the
muscle occurred. Figure 6C shows phasic inspiratory activity
of the tensor veli palatini in an awake, healthy human subject
during quiet breathing (466). Interestingly, though the activity
of the nasal dilator muscles (AN) and the genioglossus (GG)
waxed and waned, the tensor veli palatini activity was robust
and consistent.
The main action of the levator veli palatini (Fig. 6A, and
Table 1 for anatomical descriptions) is elevation of the soft
palate during swallowing. Fine nerve branches arising from
the pharyngeal branch of the vagus nerve innervate the mus-
cle. In human subjects, the respiration-related activity of the
levator veli palatini is inconsistent both within and between
subjects, and it is active during both inspiration and expi-
ration (Fig. 6D). The tracings in Figure 6D were obtained
in awake human subjects during isocapnic hypoxia, at an
arterial O2 saturation of 77% (270). In contrast, the activity
of the levator veli palatini in anesthetized dogs was consis-
tently active during the inspiratory phase of the breathing
cycle, and EMG activity increased briskly when the breath-
ing route was switched from tracheotomy breathing to nasal
breathing (Fig. 6B). The precise role of this muscle in the
context of ventilatory control and airway defense remains
unsettled.
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Comprehensive Physiology The Muscles of Breathing

(A) (B)
Hard palate
MTA EMG
palatinus
baseline
Musculus MTA EMG
uvulae levator
Tensor veli
Uvula palatini baseline
Soft palate MTA EMG
Levator veli tensor
palatini
baseline

MTA EMG
diaphragm
1 sec
TB NB

(C) (D)
Flow
inspiration
LVP EMG

EMG GG
MTA LVP EMG
MTA

EMG AN 10 sec
MTA
E
EMG TVP Airflow
I
MTA

Figure 6 Muscles of the soft palate. Panel A shows the roof of the mouth, beginning at the hard palate anteriorly, and extending dorsally
to show the soft palate, which has been transected in the schematic diagram. The main palatal muscles, the tensor and veli palatini and
musculus uvulae, are shown. Panel B shows moving time averaged EMG activities of musculus uvulae (here referred to as the palitinus),
levator and tensor palatini muscles, and the diaphragm in an anesthetized, tracheotomized dog are shown. When breathing through the
tracheotomy (left of the vertical arrow), there was a low level of inspiration-related activity in all palatal muscles, and both phasic and tonic
activities were recruited after the transition to nasal breathing, suggesting that receptors responding to airway negative pressure activate
palatal muscle motoneurons (448). Panel C shows airflow (inspiration downward) and moving time-averaged EMG activities (MTA) of the
genioglossus (GG), alae nasi (AN), and tensor veli palatini muscles (TVP) during quiet breathing in a healthy human subject; note that there is
consistent palatal muscle activity under these conditions (467). (D) Representative unprocessed and moving time-averaged EMG activity (MTA
EMG) of the levator veli palatini (LVP) in a healthy, awake human subject. The bottom trace is the airflow recording, with inspiration shown
as a downward deflection (270). Bursts of activity are observed during both inspiratory and expiratory phases of the respiratory cycle.

The fibers of the musculus uvulae (Fig. 6A and Table 1)
are wholly contained within the uvula. Contraction of the
muscle tends to shorten and widen the uvula, allowing the
soft palate to adhere to the posterior pharyngeal wall during
swallowing, which helps to ensure that food does not enter
the nasopharynx. The pharyngeal branch of the vagus nerve
innervates this muscle. We were unable to find examples of
EMG activity of this muscle in human subjects, but it is acti-
vated similarly to the other two palatal muscles in the dog
(448) (Fig. 6B, top trace, referred to as the palatinus). Since
contraction of the musculus uvulae can close the nasopharynx,
intense activation would provoke mouth breathing, and under
these conditions dilation of the oropharynx would depend on
the action of tongue and other pharyngeal muscles. Interest-
ingly, the musculus uvulae in patients with obstructive sleep
apnea (OSA) has a more anaerobic metabolic profile com-
pared to age-matched snorers, which suggests that there is
more high-intensity activation of the muscle in patients with
OSA (397).
Hyoid muscles
This group is divided into two subcategories, the infrahyoid
and suprahyoid muscles. The former group originates below
and the latter group originates above the hyoid bone, as the
names imply. It is worth noting that the hyoid is not fixed
in humans; it is attached to other bones via muscles or lig-
aments. As a consequence, the hyoid muscles may be less
effective in dilating and/or stiffening the upper airways com-
pared to rodents in which the hyoid is fixed to the mastoid

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The Muscles of Breathing Comprehensive Physiology

(A) Digastric (B)

(anterior belly) Mylohyoid
Stylohyoid 21%
Geniohyoid O2 (%) 0%
a b c d
Digastric Resp. flow
Phase 1 Phase 2
(posterior belly)
diaEMG

diaEMG, int

dEMG

dEMG, int 1 min

1.40 3.20 5.00 6.40 8.20 10.00 11.40 13.20 15.00 16.40

(C)
EMG Awake (D)
Rib cage AP

Flow Sternocleidomastoid

Awake Mylohyoid
Swallow

1 sec
(E)
NREM MPC

SH

DIA
REM
1L
VT

Control 6% CO2

Figure 7 The suprahyoid muscles. In Panel A, a schematic anatomical drawing illustrates the suprahyoid muscles, including both anterior
and posterior bellies of the digastric muscles. In Panel B, respiratory flow, EMG of the diaphragm (diaEMG) and digastric muscles (dEMG)
are shown during the transition from normoxia to anoxia in neonatal rats. Rectified and integrated versions (int) of the EMG activities are
also shown. Note the recruitment of the digastric near the end of the apnea (defined as the absence of diaEMG and flow), and continued
activation of the muscle during the autoresuscitation phase prior to a terminal apnea (380). Panel C shows the moving-time averaged
geniohyoid EMG activity, which discharged in phase with inspiratory airflow, in healthy human subjects during wakefulness (top two sets
of tracings), and NREM and REM sleep (third and fourth sets of tracings). Muscle activity was increased during NREM sleep, but declined
to waking levels or below during REM sleep. Also, note that the respiration-related activity of the geniohyoid was always much less than
that observed during a swallow, as indicated in the second set of tracings (472). Panel D shows EMG activities of the sternocleidomastoid
and mylohyoid muscles, which discharge in phase with rib cage expansion during quiet breathing in high tetraplegics, consistent with roles
for these muscle in generating inspiration (106). Panel E shows EMG activities from the middle pharyngeal constrictors, stylohyoid, and
diaphragm, together with the inspired tidal volume recording in an awake goat. The left-hand panel was recorded during quiet breathing,
and the right-hand panel was recorded during a hypercapnic challenge with 6% inspired CO2 . Note the increase in stylohyoid activity
during hypercapnia, and the pattern of expiratory discharges under both conditions (324). However, as discussed in text, stylohyoid activity
is inspiratory in the anesthetized rabbit (373).

process (220). The lack of fixation of the hyoid in humans
may contribute to the generation of OSA, but also allows
greater manipulation of the supralaryngeal space to enhance
vocalization and speech articulation (11, 130, 170, 276).
Suprahyoid muscles
As the name implies, these muscles are located rostral to the
hyoid bone and inferior to the tongue, forming the “floor of
mouth.” Suprahyoid muscles include the anterior and pos-
terior bellies of the digastric muscle and the geniohyoid,
mylohyoid, and stylohyoid muscles (see Fig. 7A and Table 1
for anatomical considerations). Interestingly, the anterior and
posterior bellies of the digastric muscle meet in the middle and
connect to one another via a tendon that is, in turn, attached to
the hyoid bone (Fig. 7A). The two bellies of the muscle have
different embryological origins, and as a result, the mandibu-
lar branch of the trigeminal nerve innervates the anterior belly,
whereas the digastric branch of the facial nerve supplies the
posterior belly. The main action of the digastric muscle is
to depress the mandible and open the mouth, but digastric
activation can also influence hyoid elevation. We were unable

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Comprehensive Physiology
to identify recordings of respiration-related digastric muscle
activity in human subjects, though recordings have been made
in neonatal rats (380). As shown in Figure 7B, there was lit-
tle digastric activity (dEMG) under baseline conditions, but
the muscle was intensely recruited during anoxia. It seems
likely that the digastric would be active in gasping, as periods
of auto-resuscitation tend to recruit all available inspiratory
muscles in an “all hands-on deck” fashion.
The right and left geniohyoid muscles lie in close appo-
sition to one another (Fig. 7A). When activated, the muscles
pull the hyoid bone forward and slightly upward, which dilates
the pharyngeal airway. The muscle also assists in swallow-
ing and can depress the mandible. The innervation of the
geniohyoid is interesting, as it is supplied by motor axons
of the first cervical nerve, but these axons travel in the ansa
cervicalis, which lies immediately adjacent to the hypoglos-
sal nerve. Given the muscle’s role in pharyngeal dilation,
its breathing-related activity has been studied extensively by
many groups of investigators. As shown in Figure 7C (traces
labeled EMG) the muscle is activated in phase with inspiration
in healthy subjects studied awake and in the supine position
(472). Close examination of the recordings also shows that
the onset of geniohyoid EMG activity precedes the onset of
inspiratory airflow, suggesting that contractions are timed to
dilate and stiffen the pharynx prior to the generation of sub-
atmospheric pressure to the upper airway lumen, which in
turn is the result of contraction of the diaphragm and other
respiratory pump muscles. Moreover, Figure 7C shows that
the geniohyoid may be more active in NREM sleep than
in wakefulness, though the activity is even greater during a
swallow.
The mylohyoid muscles (Fig. 7A) originate on the
mandible and insert onto the hyoid bone (Table 1), and
together they form the floor of mouth. The muscles are derived
from the first pharyngeal arches bilaterally and are innervated
by the alveolar branch of the mylohyoid nerves, which in
turn are branches of the mandibular division of the trigeminal
nerve. Contraction of the mylohyoid muscle elevates the hyoid
and the tongue during swallowing, and it is also involved in
mandibular depression and speech. De Troyer and colleagues
(106) recorded mylohyoid activity during quiet breathing
in high tetraplegics and found that it discharged phasically
during inspiration, and the onset of mylohyoid inspiratory
activity preceded movement of the rib cage, which is simi-
lar to the pattern observed in the geniohyoid (Fig. 7D, bot-
tom tracings). In animal models, the mylohyoid branch of
the trigeminal nerve sometimes has phasic respiration-related
activity during eupnea, though the activity often spans both
inspiration and expiration depending on the details of the
experiment (221, 419, 420). Mylohyoid nerve activity and the
corresponding activity of the mylohyoid EMG are activated
by hypoxia, or hypercapnia (415, 419, 420), or by prolonged
airway occlusion leading to hypoxia and hypercapnia. With-
holding lung inflation for a single breath in ventilated and
paralyzed animals also increases activity in the mylohyoid
nerve (28,259), suggesting that the motoneurons are normally
Volume 9, July 2019
The Muscles of Breathing
inhibited by afferent feedback from pulmonary stretch recep-
tors. The mylohyoid muscle is also recruited in response to
elevated airflow resistance (415). These observations suggest
that the suprahyoid muscles support breathing by stiffening
the upper airway under conditions where airflow resistance is
increased, or when pulmonary ventilation rises.
The stylohyoid muscles are located in front of and above
the posterior bellies of the digastric muscles on either side
below the jaw (Fig. 7A and Table 1), and like the digastric
muscle, the stylohyoid is innervated by the facial nerve. Con-
traction elevates the hyoid bone, and the muscle is very active
in swallowing. We could not find examples of respiratory-
related stylohyoid activity in human subjects. Rothstein et al.
(374) recorded inspiratory activity of the stylohyoid in anes-
thetized rabbits. Although they did not show original record-
ings, they indicate that the muscle discharged in phase with
inspiration, and that the discharge pattern was similar to
EMG activity recorded from the genioglossus muscle. In
contrast, stylohyoid activity discharged during the expira-
tory period in awake goats, and the activity was a mixture
of phasic and tonic discharge at rest. The tonic discharge was
replaced with modest recruitment of phasic expiratory activ-
ity during exposure to hypercapnia (324) (Fig. 7E). Thus,
although the breathing-related function of the stylohyoid is
unsettled, the other suprahyoid muscles support breathing by
stiffening the upper airway under conditions where airflow
resistance is increased, or when the demand for pulmonary
ventilation rises.
OSA is an exclusively human disorder, which arises from
a combination of anatomical encroachment on the upper air-
way and reduced upper airway muscle activity (including
suprahyoid muscles) during sleep (see the following text).
There is an English Bulldog model of OSA in REM sleep,
but it could be argued that the peculiar pushed in nose of the
bulldog, which makes the breed susceptible to OSA because
of nasopharyngeal airway collapse, reflects the interventions
of humans during selection of the breed’s traits (198). The
susceptibility of humans to OSA has been attributed to the
comparatively low position of the larynx within the upper
airway, which facilitates sound production for speech, but
creates a pharyngeal airway that is not supported by any rigid
structures. In addition, the hyoid is not fixed so the suprahy-
oid muscles lack a solid fixation against which to obtain a
stable mechanical advantage. Since the suprahyoid muscles
are attached to the hyoid, it is possible to test the role of a fixed
hyoid in the pathogenesis of OSA by severing the connection
of suprahyoid muscles to the hyoid apparatus. When this was
done in rats, the effect on upper airway muscles of the tongue
unexpectedly showed only a modest compensatory response,
most likely because there was no demonstrable compromise
of upper airway patency (377). These observations suggest
that the relatively rigid, short, and more linear pharynx in ani-
mal models renders them less susceptible to sleep apnea, In
contrast, the floating hyoid, elongated pharynx, and relatively
high compliance of the human pharynx makes humans more
susceptible to OSA.
1049
The Muscles of Breathing Comprehensive Physiology

(A) (B)

Hyoid
Sternohyoid
Thyrohyoid
Omohyoid, superior Genioglossus

Omohyoid, inferior Sternothyroid

Sternothyroid
(C)

Before After
10 s
Thyrohyoid

Sternohyoid

Diaphragm

1s

(D)
Tracheal
pressure

Flow

Omohyoid EMG

Figure 8 The infrahyoid muscles. Panel A is a schematic diagram showing the infrahyoid muscles. Panel B shows inspiratory-related
EMG activities of the genioglossus and sternothyroid muscle in the anesthetized rabbit; note the marked recruitment of these muscles
during a brief nasal occlusion (horizontal bar) (372). Since EMG activity increased before there was time for significant changes in
blood gases or pH, the increased activity is likely due reflex modulation of muscle activity by negative upper airway pressure or the
removal of lung volume feedback from pulmonary stretch receptors. In Panel C, the moving time averaged EMG activities of thyrohyoid,
sternohyoid, and diaphragm muscles in an anesthetized dog are shown before and after bilateral vagotomy (447). The thyrohyoid
activity was largely expiratory before vagotomy, but inspiratory after vagotomy; this pattern was not always observed—some animals
had consistent inspiratory activation both before and after vagotomy. The stylohyoid muscle discharges during the inspiratory phase under
both conditions, although the activity of this muscle was present in only two of six dogs before vagotomy, but in all dogs after vagotomy.
Panel D shows tracheal pressure, airflow, and the moving time averaged EMG of the omohyoid muscle (Omo EMG) in an anesthetized
monkey. There is minimal activity in quiet breathing, but tonic and phasic inspiratory activity is recruited during tracheal occlusion, as
denoted by the absence of flow and the large swings in tracheal pressure (136).

Infrahyoid muscles
Also called the strap muscles owing to their flattened shape,
the infrahyoid muscles originate or insert on the hyoid bone
and include the sternothyroid, omohyoid, sternohyoid, and
thyrohyoid (Fig. 8A and Table 1). All of the infrahyoid mus-
cles are innervated by motoneurons in cervical spinal cord
segments 1-3, with axons from cervical segment 1 traveling
in the ansa cervicalis and axons from cervical segments 2 and
3 in the descending cervical nerve. When these muscles con-
tract, they depress the hyoid bone, so in a broad sense, they
could be considered antagonists of the suprahyoid muscles.
The sternothyroid muscle lies deep to the sternohyoid and
its main function is to depress the larynx, which is a key aspect
of normal chewing, swallowing, and speech. Nonetheless,
studies in animal models also show clear respiration-related
activity in the sternothyroid (Fig. 8B) (372). The recordings
in Figure 8B are from an anesthetized rabbit, and though
simultaneous recordings of thoracic expansion or airflow were
not provided, the activity of the sternothyroid was inspiratory,
and paralleled that recorded from the genioglossus. Note that
the activity increased substantially in response to a brief nasal
occlusion. The reflex response is too fast to be driven by
chemoreceptors, and is consistent with a mechanoreflex.

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Comprehensive Physiology
The fibers of the sternohyoid muscle originate on the
medial, posterior portion of the clavicle, the sternoclavicu-
lar ligament and the manubrium of the sternum (Fig. 8A).
When activated, the sternohyoid results in strong depression
of the hyoid bone under conditions where the mandible is
fixed. Importantly, at least in lower mammals the sternohyoid
can pull the ribs and sternum cranially if the hyoid bone is
fixed, consistent with thoracic expansion and hence an inspi-
ratory action (106). There are many examples of respiration-
related activity of the sternohyoid muscle in animal models
(289, 303, 372, 376, 402, 427, 446, 447, 451, 453). Although
the activity is not always observed in eupnea, all studies
show increased activity with chemoreceptor stimulation or
following removal of lung volume feedback by vagotomy. For
example, in the anesthetized dog (Fig. 8C), the sternohyoid
is active in phase with inspiration, though only in some ani-
mals. Animals with activity at baseline (Fig. 8C, traces labeled
“Before”) showed a marked increase after denervation of
pulmonary stretch receptors by bilateral cervical vagotomy
(Fig. 8C, “After”) (447); similar observations have been made
in other species (28, 259). In human subjects, both the ster-
nohyoid and sternothyroid were recruited when subjects made
large volitional inspiratory efforts (164). It seems clear that
this muscle plays a significant role in maintaining upper air-
way patency during great breathing efforts.
The thyrohyoid muscle is relatively short and wide
(Fig. 8A), and its main action is to depress and fix the hyoid
bone and larynx. However, when the hyoid bone is fixed,
contraction also causes laryngeal elevation. In the anes-
thetized dog, breathing-related thyrohyoid activity is bipha-
sic, and the pattern can switch spontaneously from one with
dominant discharge in inspiration to one with dominant dis-
charge in expiration. The switch in the timing of activity could
be provoked by changing head position, but also by with-
holding lung inflation at end-expiration or after denervation
of pulmonary stretch receptors with bilateral cervical vago-
tomy, which resulted in an expiratory-to-inspiratory switch
(Fig. 8C) (447). Importantly, simultaneous electrical stim-
ulation of multiple infrahyoid muscles consistently reduces
upper airway resistance (135, 447), as does ventral traction
applied to the hyoid arch (447).
The omohyoid muscle is composed of superior and infe-
rior bellies, which are joined by a central tendon (Fig. 8A and
Table 1). The muscle’s attachments to the clavicle and hyoid
bone (as well as some fibers of the central tendon attaching to
the first rib) suggest a potential role in both thoracic expansion
as well as pharyngeal dilation. The main function of the mus-
cle is typically described as a hyoid bone stabilizer. There
are few examples of respiration-related omohyoid activity,
and we were unable to identify recordings from human sub-
jects. Figure 8D shows EMG recordings of the omohyoid in
an anesthetized monkey (136). There was some phasic inspi-
ratory activity during quiet breathing, and tracheal occlusion
strongly recruited the omohyoid motoneurons, with both pha-
sic inspiratory discharge and tonic activity increasing. Thus,
the infrahyoid muscles appear to play a significant role in
Volume 9, July 2019
The Muscles of Breathing
regulating upper airway resistance and may assist inspiration
by elevating the upper thorax.
In species with a floating hyoid, such as humans, it is pos-
sible that simultaneous activation of infrahyoid and suprahy-
oid muscles stabilizes the hyoid. As with tongue muscles, this
is another example of how coactivation of multiple muscles
acting on and/or around a given upper airway structure can
stiffen the airway. This is in keeping with the more general
principle stating that co-activation of agonist and antagonist
muscles acting on arm and leg joints leads to joint stabiliza-
tion (179).
Pharyngeal muscles
Pharyngeal muscles include the superior, middle, and inferior
constrictor muscles, the stylopharyngeus, the palatopharyn-
geus, and the salpingopharyngeus (Fig. 9, A & B). Contraction
of these muscles alters the shape or the tone of the pharyngeal
airway, and since the pharynx is compliant, as it must be for
effective swallowing, it is also a region prone to narrowing,
especially in humans, who have an unusually elongated phar-
ynx due to the descent of the larynx (313). As a consequence,
when intraluminal pressure falls below pharyngeal surround-
ing pressure (i.e., negative pharyngeal transmural pressure),
the pharynx will narrow or collapse if pharyngeal stabilizing
muscles are not recruited. Although respiration-related activ-
ity of the pharyngeal constrictor muscles is often observed,
the functional consequences of the activity remain poorly
understood, as discussed in the following text.
The superior pharyngeal constrictor muscle is flat and
quite large and has both bony and soft tissue attachment
points (Fig. 9A and B, and Table 1). The motor supply to all
the pharyngeal constrictor muscles except the stylopharyn-
geus is via the pharyngeal branch of the vagus nerve. Nerve
bundles of the pharyngeal plexus supply the superior con-
strictor’s mucosal layer, blood vessels, and sensory receptors.
Although the muscle plays an essential role in swallowing
and in shaping the airway for speech by narrowing and stiff-
ening the pharynx, it is also active during deep breathing.
In human subjects, the muscle displays mostly tonic activity
under baseline conditions, but is recruited during hypercapnia
and hypoxia (Fig. 9C) (263, 270). However, when activity is
present during eupnea, it is most often in phase with expira-
tion, which seems surprising given that the pharynx is most
prone to collapse during inspiration. The expiratory pattern
has also been observed in the dog (482), though in the rabbit
the activity occurs in phase with inspiration (374) suggesting
that airway shape may play a role in the discharge pattern.
The middle pharyngeal constrictor muscles lie caudal to
the superior constrictor and superficial to the stylopharyn-
geus (Fig. 9A and Table 1). The main action of the muscle
is to constrict during swallowing to drive boluses of food or
drink toward the esophagus. However, there is ample evidence
that, like the superior constrictor, the middle constrictor plays
an important role in breathing, both in animal models and
human subjects. As shown in Figure 9C, the human middle
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The Muscles of Breathing Comprehensive Physiology

(A) (B)
Superior
constrictor Stylopharyn
Palatophary Superigeus
ngeus or
Stylopharyngeus constrictor
Middle Salpingophary
constrictor ngeus Inferior
constrictor
Inferior
constrictor

(C) (E)
1
Normocapnia 8% CO2 9% CO2
E Flow
Airflow
I (L/s)

MTA EMG 0
SPC
MTA EMG
MTA EMG
MPC TP
MTA EMG
IPC
3s
MTA EMG
(D) SP
Levator palatini

Palatopharyngeus
10 s
MTA EMG
DIA
Respitrace
inspiration

Figure 9 The pharyngeal muscles. In Panel A, the sagittal schematic shows all the pharyngeal muscles except the salpingopharyngeus,
which is shown in the anterior view in Panel B. In Panel C, from the top down, representative traces of airflow (inspiration downward) and
moving-time averaged EMG activities (MTA EMG) of the superior (SPC), middle (MPC), and inferior (IPC) pharyngeal constrictor muscles
are shown (263). All three muscles were active during expiration, though only at high respiratory drive evoked by raising the inspired CO2
levels to 8% and then 9%. Panel D shows inspiratory-related activity of the palatopharyngeus muscle in an awake, upright, human subject
with obstructive sleep apnea (307). The activity of the levator palatini and a chest wall motion recording (respitrace, inspiration upward) are
also shown. The EMG activities are moving-time averages. Panel E shows inspiratory airflow and moving time averaged EMG activities of
thyropharyngeus (TP), stylopharyngeus (SP), and the diaphragm (Dia) in an awake goat. Note that stylopharyngeus activity occurs during
inspiration in eupnea and is abolished during a spontaneous apnea, which is defined as the absence of airflow and diaphragm EMG
activity (144).

pharyngeal constrictor is activated similarly to the supe-
rior constrictor: both muscles are minimally active under
baseline, eupneic conditions, and discharge phasically dur-
ing expiration when hypercapnia is used to increase res-
piratory activity. Similar observations were made in the
awake goat (324), though in the anesthetized rabbit (373)
and monkey (375) middle pharyngeal constrictor activity was
in phase with inspiration. An interesting observation is that
in ketamine-anesthetized monkeys, all three pharyngeal con-
strictors showed respiration-related discharge when the ani-
mals were supine or seated, but when the monkeys were awake
the activity was lost. This could indicate that the anesthesia
depressed alveolar ventilation, increased arterial CO2 partial
pressure, and stimulated muscle activity or that anesthesia
released other stimulatory influences that increased drive to
the motoneurons (375).
The inferior pharyngeal constrictor is often considered to
be two separate muscles: a more superior part that originates
on the thyroid cartilage and a more inferior part that origi-
nates on the cricoid cartilage (Fig. 9A and B, and Table 1).
Thus, some anatomists consider the structure to be composed
of a “thyropharyngeal” muscle and a “cricopharyngeal mus-
cle”. Both parts of the muscle extend from their respective
origins in a posterior-medial direction to insert on the pharyn-
geal raphe. Like all pharyngeal constrictor muscles, the infe-
rior constrictor is important for swallowing, but also shows
respiration-related activity in humans (Fig. 9C) (263), anes-
thetized monkeys (375), anesthetized rabbits (373), sleeping

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Comprehensive Physiology
rats (402), awake goats (324), and awake lambs (120). The
activity was expiratory in the humans, lambs, goats, rabbits,
and monkeys and inspiratory in the rat. In most species, the
activity can be biphasic depending on the experimental con-
ditions and can also be altered by changes in posture.
Given the above, the breathing-related mechanical con-
sequences of pharyngeal constrictor muscle activity are not
entirely clear. Kuna and colleagues (264) stimulated the motor
nerve supply to the pharyngeal constrictors while measuring
pharyngeal luminal pressure in decerebrate, tracheotomized
cats. They found that stimulation dilated the pharynx at low
lung volumes but constricted it at higher volumes. Addi-
tional experiments showed that the radial force produced
by the constrictors was outwardly directed at low lung
volumes and inwardly directed at high volumes. From this, the
authors speculate that the expiratory activity of the muscles
could provide a braking action on expiratory airflow when
lung volume is high but would dilate the pharynx when lung
volume is low. Obviously, more experiments—especially on
human volunteers—are needed for a full understanding of the
mechanical actions of the pharyngeal constrictor muscles, as
they may play an important role in protecting the pharynx in
persons with OSA.
The palatopharyngeal muscles are covered with mucous
membrane and form the posterior tonsillar pillars. Each mus-
cle is composed of two main fascicles: a posterior fascicle
originating at the mucous membrane on the posterior surface
of the soft palate approximately at the midline, and an ante-
rior fascicle that emerges from the posterior boundary of the
hard palate and also meets its contralateral partner at the mid-
line (Fig. 9B). The muscle then passes inferiorly and laterally
and inserts into the posterior border of the thyroid cartilage
adjacent to fibers of the stylopharyngeus.
The muscle pulls the pharyngeal walls upward and
medially during swallowing, but it also shows respiration-
related discharge. Mortimore and Douglas described pha-
sic inspiratory-related palatopharyngeal activity in healthy,
awake subjects (Fig. 9D) (308) and subjects with OSA
(306, 307). They also showed that the activity tended to be
highest when subjects were nose breathing in the supine
posture, and that the application of negative pressure lead
to increased activity within 100 ms, consistent with a reflex
response to negative pharyngeal pressure. The palatopharyn-
geus was active in phase with inspiration in anesthetized
rabbits (373), but during the expiratory phase in exercising
horses (209). These data suggest that depending on the unique
features of pharyngeal anatomy, the palatopharyngeus can
modulate both inspiratory and expiratory flow resistance.
The stylopharyngeus is a long, thin cylindrical muscle
that originates on the styloid process, and as it descends, it
passes between the superior and middle pharyngeal constric-
tor muscles. The majority of the fibers insert into the pos-
terior border of the thyroid cartilage, but some fibers merge
with one of the constrictor muscles or the palatopharyngeus.
The stylopharyngeus is innervated by the motor branch of the
glossopharyngeal nerve, which passes over the lateral aspects
Volume 9, July 2019
The Muscles of Breathing
of the muscle. Contraction of the stylopharyngeus elevates
both the larynx and pharynx, which is consistent with an
important role in swallowing. We could not find recordings
of stylopharyngus activity in human subjects, but detailed
studies have been done in the awake goat model. As shown
in Figure 9E, moving-time averaged EMG activities of thy-
ropharyngeus (TP), stylopharyngeus (SP), and the diaphragm
(DIA), stylopharyngeus activity is inspiratory-related during
eupnea, and its activity is abolished during a spontaneous
apnea, defined as the absence of airflow and diaphragm EMG
activity (144).
The salpingopharyngeus muscle originates on the medial
cartilaginous section of the Eustachian tube, from where it
descends to merge with the posterior fascicle of the palatopha-
ryngeus (Fig. 9B). The main action of the muscle is to raise
the lateral pharyngeal walls and the larynx during swallowing,
as well as opening the pharyngeal orifice of the Eustachian
tubes to equalize pressure in the inner ear. The breathing-
related role of the muscle is poorly understood. We are aware
of only one study, wherein inspiratory discharge was recorded
in two spontaneously breathing anesthetized rabbits (373).
The breathing-related function of salpingopharyngeus mus-
cle contraction is unknown, though it is possible that the
inspiratory activity of the muscle observed in the rabbit helps
to stiffen the pharyngeal walls.
Laryngeal muscles
The intrinsic muscles of the larynx are often considered as
three functional groups: those that can modify the size of the
rima glottidis (“glottis”), those that regulate tension in the
vocal ligaments, and those that alter the size of the laryngeal
inlet. Because the laryngeal muscles can widen or narrow the
glottal aperture, they play an important role in the regulation
of airflow resistance and the coordination of breathing and
swallowing. As a result, their breathing-related activity has
been studied extensively. Laryngeal muscles with a particu-
larly well-documented role in breathing include the posterior
cricoarytenoid, thyroarytenoid, and the cricothyroid muscles.
All of the laryngeal muscles originate on one of the laryngeal
cartilages (Fig. 10A and Table 1), and insert into cartilage
or other laryngeal muscles. Various branches of the recurrent
laryngeal nerve provide motor innervation to all the intrin-
sic laryngeal muscles, with the exception of the cricothyroid,
which is innervated by the external branch of the superior
laryngeal nerve.
The posterior cricoarytenoid muscles are each composed
of two bellies, one lateral and more rostral and one more
medial and caudal, and they have different insertion points
(Fig. 10B and C, and Table 1). The more rostral belly
rotates the arytenoid cartilage laterally and backward, which
increases tension in the vocal ligaments. The more caudal
belly draws the arytenoid cartilages laterally and widens the
glottis, producing a triangular shape that is noticeable dur-
ing forced inspiratory efforts (61); thus, this belly is often
considered the “true laryngeal dilator muscle.” The inferior
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The Muscles of Breathing Comprehensive Physiology

(A) (B)

Epiglottis Posterior
Transverse
Thyroid cartilage cricoarytenoid
arytenoid
Arytenoid cartilages muscle
muscle
Cricoid cartilage Lateral
Corniculate cartilages Thyroarytenoid cricoarytenoid
muscle muscle

(C) (D)

Oblique arytenoid
muscle

Transverse arytenoid
muscle Cricothyroid muscle
vertical belly

Cricothyroid muscle
oblique belly
Posterior
cricoarytenoid
muscle

Figure 10 The laryngeal muscles. For anatomical orientation, the laryngeal cartilages are shown from anterior (left) and posterior vantage points
in Panel A, a superior view in Panel B, and a dorsal view in Panel C. Panel D shows, from top down, tidal volume, airflow (inspiration down),
and raw and moving-time averaged EMG activities of the posterior cricoarytenoid muscle in healthy human subjects. As with the thyroarytenoid,
posterior cricoarytenoid activity during quiet breathing is brisk, and there is marked recruitment during progressive hypercapnia, as evoked with
7% and 9% CO2 in the inspired gas (260). Panel E shows EMG recordings of the levator veli palatini (LVP), the lateral cricoarytenoid (LCA), and
rib cage expansion in an anesthetized dog during the transition from eupnea to progressive hypercapnia. Note that the LCA was active during
expiration in eupnea, but was markedly reduced in hypercapnia—the opposite of the response of the LVP to hypercapnia (251). Panel F shows the
activity of the arytenoideus muscle in a healthy adult human subject that transitioned spontaneously from eupnea to rapid, shallow breathing. The
unprocessed and moving time averaged EMG recordings are shown, and the upper two traces are airflow (expiration upward) and tidal volume,
respectively. The muscle is active during eupnea, and discharges in phase with expiration (262). Drive to the muscle was reduced during the
period of rapid shallow breathing, and expiratory glottic area increased, consistent with a drop in expiratory flow resistance. As explained in the
text, it was not possible to determine whether the electrodes were located in the transverse or the oblique arytenoid, as the muscles are very small
and closely apposed to one another. Panel G shows representative recordings of unprocessed and moving time averaged EMGs of the lateral
cricoarytenoid (CT) muscle and tidal volume (inspiration upward) in a human subject studied during progressive hyperoxic hypercapnia. Segments
of the experiment at baseline and at two levels of increased ventilatory drive are shown. The rate of pulmonary ventilation in the three segments
was 8.0, 18.1, and 26.5 L/min. Note that the activity of the lateral cricoarytenoid occurs during inspiration in eupnea, and that both peak phasic
and tonic expiratory activities increase in hypercapnia (469). Panel H shows unprocessed and moving time averaged thyroarytenoid muscle EMG
recordings and airflow (inspiration down) in a young, healthy human subject breathing quietly (“nonloaded”) and against three successively larger
inspiratory resistive loads (232). Note the consistent, inspiration-related activity during quiet breathing and progressive recruitment as the resistive
load increased.

branch of the recurrent laryngeal nerve supplies the motor
innervation to the muscle.
As shown in the EMG recordings in Figure 10E, the pos-
terior cricoarytenoid is active in inspiration, and the pha-
sic activity increases with hypercapnia (260). Moreover, in
human subjects, the higher the posterior cricoarytenoid activ-
ity, the wider the glottis, which in turn leads to a reduction
in airflow resistance (48, 50, 80, 82, 137-139). One or both of
these observations have been made by many investigators, and
in many species (5,25,38,48,51,80,82,140,192,231,251,254,
260, 261, 324, 349, 352, 384, 385, 401, 424, 425, 454, 480, 489).
Further, voluntary sniffing maximally opened the vocal folds
as a result of rapid, phasic recruitment of both the pos-
terior cricoarytenoid and the cricothyroid in humans. This
‘sniff’ test is used clinically to test laryngeal abductor mus-
cle function (347). In anesthetized or decerebrate animal

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Comprehensive Physiology The Muscles of Breathing

(E) Normocapnia 7% CO2 9% CO2

Volume

Flow
expiration

EMG
PCA

MTA EMG
PCA
10 s
(F) EMG LVP 100 !V

EMG LCA 200 !V

Rib cage
inspiration
5s

(G) 0.8
Flow
0.0
(L/s)
–0.8
1.4
Volume
(L)
0

AR EMG

45
AR MTA
EMG
0
2.1
Glottic
area
0.4
10 s

Figure 10 (Continued )

models (25, 26), hypercapnia increased posterior cricoary-
tenoid activity and was associated with increased vocal cord
abduction and a drop in upper airway resistance, and this
was true both before and after denervation of sensory afferent
feedback from pulmonary stretch receptors.
By adducting the vocal cords, activation of the glottic con-
strictor muscles elevates airflow resistance and reduces the
rate of expiratory airflow (360). The paired lateral cricoary-
tenoid muscles originate on the ipsilateral cricoid cartilage
and insert onto the muscular portion of the arytenoid cartilage
(Fig. 10A and B). The muscles rotate the arytenoid carti-
lages medially and contribute to adduction of the vocal cords.
There are very few recordings of this muscle under condi-
tions where breathing was also monitored. In an interesting
study in human subjects, EMG activities of seven intrinsic
laryngeal muscles were recorded simultaneously (207).
Although the study was focused largely on voice produc-
tion, subjects were asked to voluntarily increase their rate and
depth of breathing. Both left and right lateral cricoarytenoid
muscles were recruited in 9 of 10 subjects under these con-
ditions. Koizumi et al. (251) reported, in anesthetized dogs,
that the lateral cricoarytenoid was active during eupnea but
markedly reduced in response to progressive hypercapnia,
which was the opposite of the response in the levator veli
palatini (Fig. 10F). This is consistent with the muscle’s action
as a laryngeal adductor, as a reduction in lateral cricoary-
tenoid activity during hypercapnia would widen the glottis
and promote expiratory airflow.
The transverse arytenoid is an unpaired, thin sheet of
muscle that overlies the posterior surface of the arytenoid

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The Muscles of Breathing
(H)
CT EMG
CT iEMG
VT
1L
(I) Nonloaded Load 1
EMG
TA
MTA EMG
TA
Flow
expiration
Figure 10 (Continued )
cartilages (Fig. 10B and C). It extends from the lateral border
of one arytenoid cartilage to the lateral border of the con-
tralateral arytenoid cartilage. When the muscle contracts it
brings the arytenoid cartilages together, thereby narrowing
or closing the glottis; thus, it is a glottic adductor. There are
limited recordings of the transverse arytenoid muscle as it
is extremely difficult to distinguish its activity from that of
the oblique arytenoids (see the following text). Kuna et al.
(262) studied arytenoid activity in human subjects, though
they were “unable to determine whether the electrodes were
located in the transverse arytenoideus and/or oblique ary-
tenoideus because of the very small size and intimate rela-
tionship of these muscles.” As a result, they described their
recordings as “arytenoideus EMG recordings” to reflect this
uncertainty. The muscle was active under eupneic conditions
in 11 of the 14 subjects studied, with recordings from one
of these subjects shown in Figure 10G. In most subjects, the
onset of activity was in the latter half of the inspiratory phase,
and it persisted throughout the expiratory phase. Figure 10G
also shows a substantial decrease in activity as the subject
transitioned, spontaneously, from eupnea to a more rapid and
shallow breathing pattern. This coincided with an increase in
expiratory glottic area (Fig. 10G). One explanation is that the
low lung volumes associated with shallow breathing lead to
reduced expiratory elastic recoil pressure, so reducing drive
to the arytenoideus and dilating the glottis would mitigate the
drop in expiratory flow caused by the reduced recoil pressure.
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Comprehensive Physiology
5s
Load 2 Load 3
5s
The sensory component of the reflex leading to the switch is
unknown. Moreover, since the activity of the transverse and
oblique arytenoid muscle could not be distinguished, firm con-
clusions cannot be drawn and additional studies are needed.
Muscles that regulate the tension in the vocal cords include
the cricothyroid, thyroarytenoid, and the posterior cricoary-
tenoid muscles. Since the breathing-related activity of the
posterior cricoarytenoid has been discussed above, we con-
fine this discussion to the cricothyroid and the thyroarytenoid
muscles. The cricothyroid muscle originates on the anterolat-
eral aspect of the cricoid cartilage and attaches to the inferior
horn of the thyroid cartilage (Fig. 10A and D). As indicated
above, the external branch of the superior laryngeal nerve
innervates the muscle, making it the only intrinsic laryngeal
muscle that is not innervated by the recurrent laryngeal nerve.
Contraction of the cricothyroid muscle stretches and stiffens
the vocal cords and may also widen the vocal cord opening by
pulling the thyroid cartilage downward and over the cricoid
cartilage (291). This widening of the glottic opening suggests
that the cricothyroid and posterior cricoarytenoid muscles are
agonists, serving to decrease resistance to inspiratory airflow.
The cricothyroid is active in inspiration during quiet breath-
ing in healthy human subjects (Fig. 10H, left panel), and
both peak phasic and tonic activity increase systematically
during progressive hyperoxic hypercapnia (middle and right
panels) (469). The rise in activity paralleled the rise in minute
ventilation, consistent with a role in abduction of the glottis
Volume 9, July 2019
Comprehensive Physiology
as inspiratory flow rates increase. The rise in both phasic and
tonic discharge is consistent with single motor unit recordings
in healthy human subjects (77), in whom 45% of cricothy-
roid motor units discharged phasically and the remainder
tonically. Moreover, the phasic units showed several pat-
terns: inspiratory activity that continues into early expiration,
expiratory activity that continues into inspiration, and tonic
discharge.
The thyroarytenoid muscles originate on the lower half
of the thyroid cartilage on each side and insert on the ante-
rior surfaces of the arytenoid cartilage (Fig. 10A and B). The
muscles lie above the vocal cords. Often the muscle’s lower
fibers are referred to as the “vocalis,” as the fibers insert into
the vocal process of the arytenoid cartilage, while the upper
fibers are often termed the vocal muscle, as these fibers are
very active during speech. A variable proportion of the thy-
roarytenoid muscle fibers extend into the aryepiglottic fold,
where some of the fibers reach the margins of the epiglottis.
These fibers are sometimes described as a separate muscle
called the thyroepiglotticus. This somewhat variable structure
translates into functional variations as well. The main effect
of contraction is to shorten and slacken the vocal cords for
the control of pitch during speech. However, when the more
lateral portions of the muscle contract, the arytenoid carti-
lages rotate inward, which narrows the glottis. This action
has been the focus of the muscle’s respiration-related control,
as the size of the glottic aperture is an important regulator of
airflow resistance. The thyroarytenoid muscle is active during
quiet respiration, and both phasic inspiratory and tonic motor
unit activities have been observed in human subjects (77),
though the predominant pattern in human subjects and ani-
mal models is phasic expiratory activity (232) (Fig. 10I). In
humans, the expiratory activity has been shown to narrow the
glottis, increase expiratory resistance, and reduce expiratory
airflow. Together, these actions serve to dynamically con-
trol functional residual capacity and contribute to the mainte-
nance of alveolar volume during eupnea (5,231,261). Reports
of reduced thyroarytenoid activity during hyperpnea induced
with hypercapnia or hypoxia in healthy human subjects are
consistent with the important role of the thyroarytenoid in the
dynamic control of expiratory airflow resistance (232).
However, note in Figure 10I that progressive increases
in expiratory flow resistance (“Load I, Load II, Load III”)
were accompanied by increased, rather than decreased thy-
roarytenoid activity (232). This is consistent with studies by
Daubenspeck and Bartlett (95) and Brancatisano et al. (49),
which also demonstrated increased expiratory glottic narrow-
ing during the application of expiratory loads. Interestingly,
Insalco et al. (232) showed a strong correlation between expi-
ratory duration and thyroarytenoid peak EMG activity as well
as glottic narrowing, suggesting that the thyroarytenoid activ-
ity determined the expiratory duration by increasing expira-
tory flow resistance and retarding expiratory flow. In con-
trast to these studies, Rattenborg (355) found that the glottic
aperture increased during the application of expiratory resis-
tive loads. Thus, there seems to be a need for more detailed
Volume 9, July 2019
The Muscles of Breathing
studies of the role of thyroarytenoid activity in the control of
expiratory flow resistance.
Muscles that alter the size of the laryngeal inlet include the
oblique arytenoids, the aryepiglotticus, and the thyroepiglot-
ticus. The oblique arytenoid muscles are paired and lie on
top of the transverse arytenoid (Fig. 10C). Each muscle orig-
inates on the base of one arytenoid cartilage, and inserts onto
the apex of the contralateral cartilage, such that the mus-
cles form an “x.” These muscles are active during cough and
swallowing, acting as a sphincter that closes the larynx. As
discussed earlier, we are unaware of recordings of the oblique
arytenoids alone. Some fibers of the oblique arytenoids con-
tinue around the lateral margin of the cartilage and extend into
the aryepiglottic fold to make up what is sometimes described
as a separate muscle, the aryepiglotticus. The aryepiglotticus
acts as an oblique arytenoid synergist to close the laryngeal
inlet, presumably by pulling the margins of the epiglottis tight
against the aryepiglottic fold and preventing the epiglottis
from being sucked inward during inspiration. Similarly, some
fibers of the thyroarytenoid muscle extend into the aryepiglot-
tic fold and insert into the epiglottis, and this bundle of fibers
is defined as the thyroepiglottic muscle. The thyroepiglotti-
cus widens the laryngeal inlet. However, studies from human
cadavers indicate that these small muscles may or may not be
discernible, and when they are found, the thickness of the fiber
bundles is highly variable (358). Thus, the function of these
mysterious, small, and variably present muscles remains con-
troversial. Nonetheless, the role of these muscles in breathing
deserves further study, especially when one considers their
possible role in inspiratory stridor (283).
The activity of abducting and adducting laryngeal muscles
is usually carefully coordinated so that both inspiratory and
expiratory laryngeal resistance is optimized to match respira-
tory demands. However, laryngospasm, which is a respiratory
protective reflex elicited by stimulation of the supra- and pos-
sibly infralaryngeal receptors, disrupts this usual coordina-
tion and leads to airway obstruction. Laryngospasm occurs in
adults, but it is more common in young children and infants.
The laryngeal obstruction is caused by intense activation of the
lateral cricoartenoid and thryroaretenoids (laryngeal adduc-
tors) and the cricoarytenoids, which stiffen the vocal cords
(269). Laryngospasm may complicate induction of anesthe-
sia and intubation, and laryngeal anesthesia, which blocks
laryngeal receptors, may reduce the risk of eliciting this inap-
propriate activation of laryngeal constrictors (295).
Thoracic muscles
The traditional anatomic description of thoracic muscles
includes all muscles that move the ribs. These include mus-
cles that connect adjacent ribs (intercostal group), muscles
that span two or more ribs (the subcostalis muscles), those
that connect the ribs to the sternum (transversus thoracis or
“triangularis sterni”) (110) and muscles that connect the ribs
and vertebrae (the levator costae and the serratus muscles)
(Fig. 11, panels A and B). All of these muscles act to change
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The Muscles of Breathing Comprehensive Physiology

(A) (C)

A
Internal insp.
intercostals
Airflow

Transversus Ribcage
thoracis

Diaphragm Dorsal external

intercostal (3)

(B) (D)

Flow
Tidal volume
Pectoralis
Internal minor
intercostals A

External
intercostals Serratus
anterior

Figure 11 The thoracic muscles. Panels A and B are schematic diagrams showing those thoracic muscles that
have documented respiration-related activity. Panel C shows airflow (inspiration upward), ribcage movement (inspi-
ration up), and the unprocessed and moving time averaged EMG signals of the dorsal external intercostal muscles
from the third intercostal space during quiet breathing in a healthy human subject. The activity is clearly in phase
with inspiration (109). Panel D shows intramuscular EMG recordings from the third, right intercostal space. The
upper tracings show inspiratory activity recorded from the superficial layer, and the bottom traces show expiratory
activity in a deeper layer. The airflow and tidal volume recordings are superimposed on each set of EMG record-
ings (arrows). Inspiration is upward for both flow and volume. This experiment indicates that expiratory activity
predominates in the deep layers even in the rostral intercostal spaces, Panel F (434). Panel E shows tidal volume
(inspiration upward), the moving time average EMG of an external intercostal muscle from the sixth interspace, and
the moving time average and unprocessed EMG of the internal intercostal muscle from the ninth intercostal space,
also on the left-side, in a healthy human subject. Note that forced exhalation of the expiratory reserve volume (ERV)
causes marked recruitment of the internal intercostal muscle. While the activity of both muscles was absent or mini-
mal in eupnea, when the subject held his breath at end-expiratory lung volume while rotating to the left, tonic EMG
activity was evoked in the internal intercostal muscle and phasic expiratory activity was accentuated. This suggests
that increasing synaptic input to the internal intercostal motoneuron pool by twisting brought the neurons closer to
firing threshold. Adapted, with permission, from (367). Panel F is a schematic of the right side of the chest showing
where intercostal activity was most consistently found during quiet breathing (dotted area, inspiratory; hatched area,
expiratory), with the number of observations made at each location indicated. The two points marked “D” indicate
the site of electrode placement for diaphragm recordings. In general, the upper parasternal intercostals were active
only during inspiration, while the caudal and more lateral spaces were active during expiration (434). This obser-
vation, made in 1960, was largely confirmed in studies by De Troyer and colleagues, which are summarized in
Panel G. These data show the relation between airway opening pressure and the activities of external, internal,
and parasternal intercostal muscles recorded from four different intercostal spaces (110). Note that parasternal
muscles discharge only in inspiration; external intercostals in in the rostral spaces are active during inspiration,
but in the caudal spaces (T8 and below) they discharge during the expiratory phase. Internal intercostal muscles
are consistently active in the expiratory phase. The recordings in Panel H show the anteroposterior diameter of
the abdomen (increase upward, indicating inspiration) and EMG recordings of the triangularis sterni (or transversus
thoracis), the external oblique abdominal muscle, and the “deeper abdominal muscle layer” from a healthy 66-year-
old subject studied in the standing position are displayed. In this subject, all three muscles were phasically active
during expiration (143). Panel I shows (from top down) representative recordings of mouth pressure, inspiratory
flow, tidal volume, and the moving-time averaged EMG of the pectoralis major muscle in a young healthy subject. In
the left-hand panels, the subject was asked to make an inspiratory effort at 80% vital capacity against an occluded
airway, while in the right-hand panels the subject breathed against a large inspiratory resistance (66) (see text for
more details). Panel J shows representative surface EMG tracings from the right sixth intercostal space and the right
serratus anterior muscles in a young, healthy, human subject instructed to take deep breaths so that the inspired
volume approached the inspiratory capacity. Inspiration is represented by a downward deflection in the airflow
signal and an upward deflection in the tidal volume trace (356).

1058 Volume 9, July 2019

Comprehensive Physiology The Muscles of Breathing

(E)
Volume ERV
700 mL

MTA EMG
ext. intercostal

MTA EMG
int. intercostal
EMG
int. intercostal
Left turn
10 s

(F) (G)
–4 Parasternal
External
2 Internal
–3
6 14
4
–2
2 10 22
–1

Δ Pao (cmH2O)
3 10 12
0
2 7 12 15
1
2 2
1 4
3 10 10
3
3 2
3 3 2
4
4
15
5
2 5 2
6
MCL 2 4 6 8
D Intercostal space
MAL

(H) Abdomen AP

EMG
triangularis
sterni
EMG
Ext. oblique
EMG
Deeper abdominal
layer 1s

(I) (J) EMG

intercostal Exp. Insp.
A B
Mouth pressure
25
(cmH2O) 40 12 mV
EMG
Inspiratory 0.5 0.5 Serratus anterior
flow (L/s)

Tidal volume 4.0 1.0

(L) Flow
expiration
MTA EMG 12 L/s
pectoralis major Tidal volume
(L)
5L

Figure 11 (Continued )

Volume 9, July 2019 1059

The Muscles of Breathing
rib cage dimensions, so they are often defined as respiratory
“pump muscles.” The respiration-related activity of most of
these muscles has been explored, and key features will be
described in the following text. Before discussing the tho-
racic muscles, we note that the diaphragm has been grouped,
arbitrarily, with the abdominal muscles.
Intercostal muscles are arranged in thin sheets located
between each of the ribs and are divided into three groups:
the external, internal, and innermost intercostals. Whether the
innermost intercostals are separate muscles or part of the inter-
nal intercostal layer is unsettled; there is considerable anatom-
ical variability observed between species as well as within a
species, including humans (363). The fibers of the innermost
intercostals have the same orientation as the internal inter-
costals, so both muscles likely play a role in rib depression
and thus exhalation. The intercostal nerves and blood vessels
supplying a given intercostal space lie on the surface of the
innermost intercostals, which in turn lie on the surface of the
parietal pleural membrane. The intercostal nerves travel along
the rostral rib of each intercostal space, with each intercostal
nerve sending out fine branches that supply each of the inter-
costal muscles. Thus, the whole intercostal nerve carries axons
to all three muscles within its target intercostal space, which
explains why recordings of whole intercostal nerve activity
are often composed of both inspiratory and expiratory bursts
(see the following text).
In humans, the external intercostals originate on ribs 1 to
11 and insert on ribs 2 to 12 (Fig. 11B and Table 1). Their
mechanical action is complex and has been reviewed in detail
in two recent publications (102, 110). In brief, if each inter-
costal space is considered to comprise a rostral and a cau-
dal rib, each external intercostal muscle elevates its caudal
rib. Thus, the collective activation of all external intercostal
muscles moves the ribs rostrally (elevation) and rotates them
anteriorly, which expands the transverse dimensions of the rib
cage. These actions define external intercostals as inspiratory
muscles. There are, however, some interesting functional spe-
cializations. For one, marked regional variations exist across
both the rostro-caudal and dorsal-ventral dimensions (109).
For example, the external intercostals located close to the
sternum, the “parasternal intercostals,” appear to play a larger
role in thoracic expansion than more distal regions of the
muscle and to have a lower recruitment threshold when ven-
tilatory demand increases [for a detailed review, see (110)].
The parasternals extend from the sternum to the costochon-
dral joint, and in this region, all the muscle fibers are derived
from the internal intercostal muscle layer. However, the mus-
cle in the same intercostal space, but on the dorsal surface,
appears to be derived only from external intercostal muscle
fibers. The dorsal region also includes a specialized agonist
muscle known as the levator costae, which extends from the
transverse process of the spine to the adjacent, caudal rib; we
categorize this as a back muscle, and it is discussed below.
Whether or not the external intercostals contribute to
eupneic breathing in healthy human subjects has long been
debated. However, recent studies suggest that the parasternals
1060
Comprehensive Physiology
are active during eupnea in most subjects (109, 160, 189, 223,
224, 379). For example, DeTroyer and Estenne found that
parasternal intercostals were “always active” during quiet
breathing, and that their activity pattern was a ramp-like
increase throughout inspiration with continued discharge into
the early part of the expiratory period (104) (see Fig. 11C).
The ramp like pattern of the EMG could be the result of
recruitment and/or an increase in firing rate of motor units
throughout the inspiratory phase. Gandevia et al. (159) found
that external intercostal motor units increased their firing rate
monotonically throughout inspiration both in quiet breathing
and during hypercapnia, but the firing rate increased modestly,
from 10 to about 12 Hz. Though whole muscle EMGs were
not recorded, measures of rib cage expansion increased sub-
stantially, suggesting that increasing external intercostal force
is dominated by motor unit recruitment, with increased firing
rate playing an important though quantitatively lesser role.
Posture is also an important determinant of the magni-
tude of intercostal muscle activity. Druz and Sharp (129)
showed that, in healthy human subjects, parasternal inter-
costals had both phasic and tonic discharge when subjects
were upright, but both patterns of activity declined signifi-
cantly when the subjects switched to the recumbent posture.
In contrast, Wanke et al. (463) showed that for a given level
of ventilation, the supine posture was associated with greater
drive to the intercostal (and diaphragm) muscles compared to
the seated position, probably reflecting the increased abdom-
inal loading of inspiratory muscles associated with the supine
posture. In summary, external intercostal muscles are active
during eupnea in most human subjects that have been stud-
ied, are among the first inspiratory muscles recruited when an
increase in tidal volume is needed, and both external and
parasternal intercostal muscles contribute to the increased
tidal volume (359, 484). There are considerable variations
in drive to external intercostal muscles depending on the
anatomic location of the muscle, and other factors such as
posture, rib cage compliance, etc.
The internal intercostal muscles lie beneath the external
intercostals in each interspace, and their fibers are oriented
approximately 90◦ to the axis of the external intercostal mus-
cle fibers (Fig. 11B). They originate on ribs 2-12 and insert
on ribs 1 to 11. Accordingly, their mechanical actions are
opposite to those of the external intercostals. When activated,
they move each rostral rib caudally (depression) and rotate the
ribs both caudally and posteriorly, which decreases the trans-
verse dimensions of the rib cage. This action compresses the
lungs and thus promotes exhalation. It is widely believed that
these muscles are quiet during eupnea in healthy mammals as
the natural elasticity of the lungs generates sufficient inward
recoil at the onset of the expiratory phase of the breathing
cycle to promote passive exhalation. However, in his classic
study published in 1960 (434), Taylor found eupneic expira-
tory activity in internal intercostal muscle layers in the lateral
regions of interspaces 8 to 11 in humans (Fig. 11D). Whitelaw
and colleagues also reported “low-grade” internal intercostal
activity in the eighth interspace during eupnea (367, 471),
Volume 9, July 2019
Comprehensive Physiology
and that the activity increased when subjects were asked to
rotate their trunk to the same side of the body from which
the recordings were made (Fig. 11E). These findings suggest
that at least some of the internal intercostal motoneurons used
for breathing and trunk rotation are the same, and that trunk
rotation may have increased excitability of the motoneurons
and amplified the descending respiratory-related drive. An
interesting point is that more rostral parasternal muscles are
biased toward inspiration, even though the muscle fibers in
that region are derived from the internal intercostal muscle
layer as discussed above. Taylor also found that, with some
exceptions, the upper parasternal intercostals were active dur-
ing inspiration, while the caudal and more lateral parasternal
intercostals were active during expiration (434) (Fig. 11F).
These observations, made in 1960, were largely confirmed
in studies by De Troyer and colleagues, which are summa-
rized in Figure 11G. This figure shows the relation between
airway opening pressure and the activity of external, inter-
nal and parasternal intercostal muscles recorded from four
different intercostal spaces (110). The data support the idea
that, in human subjects, inspiratory activity in the more ros-
tral external and parasternal intercostal muscles predominates
in eupnea, whereas expiratory activity predominates in the
more caudal interspaces. However, fascinating observations
by Sibuya et al. (404) raise some very interesting questions.
They studied patients with brachial plexus injury in the inter-
costal nerves from the third and fourth thoracic interspaces
were cut and used to reinnervate the biceps brachii muscles.
EMG recordings from the biceps showed eupneic, expiratory
bursting in six of the eight patients and mixed inspiratory and
expiratory activity in the other two patients, though expiratory
activity was much stronger in these two individuals. More-
over, expiratory activity increased during hypercapnia. Given
these findings, how can inspiratory activity predominate in
the upper intercostal spaces in intact humans? Answering
this question will require carefully designed and executed
experiments. Finally, there is a strong consensus that internal
intercostal muscles are recruited whenever there is a demand
for more rapid and/or forceful lung emptying (e.g., exercise,
coughing, etc., (125, 234).
The triangularis sterni muscles (also known as the
transversus thoracis muscles) originate on the dorsal surface
of the xiphoid process and the caudal region of the dorsal
sternum and insert on either side of the rib cage into the
second to sixth costal cartilages (Fig. 11A). Upon contrac-
tion, these muscles depress the ribs and narrow the thorax,
assisting expiration. In dogs, triangularis sterni muscles were
always active in eupnea, and consistently discharged during
the expiratory period. The activity of the triangularis sterni
commenced shortly after the inspiratory parasternal activ-
ity ceased, increased during the early expiratory period, and
continued at a steady level until expiration was terminated
(112). Careful mechanical measurements confirmed that con-
traction of the muscle elevated the sternum, depressed the
ribs, and decreased lung volume, effects that are consis-
tent with an expiratory function. Triangularis sterni activity
Volume 9, July 2019
The Muscles of Breathing
increases during brain hypoxia (74), exercise (7) and hyper-
capnia (7, 225, 328, 390, 409). In contrast to animal mod-
els, there is no eupneic triangularis sterni activity in human
subjects studied in the supine posture, though volitional expi-
ratory maneuvers reliably recruited the muscle (113). In con-
trast, 16 of 20 subjects studied while standing showed pha-
sic, expiratory-related activity in the triangularis sterni (143)
(Fig. 11H). Thus, as in animal models, the human triangu-
laris sterni is an important muscle under conditions of active
expiration and plays an important role in compensating for
the adverse effects of gravitational forces on the diaphragm
in the upright posture.
The pectoralis major muscle has two heads: a clavicular
head, which originates on the anterior border of the clavicle,
and a sternocostal head, which arises from the anterior sur-
face of the sternum, the upper six costal cartilages, and the
aponeurosis of the external oblique muscle (Fig. 11B). The
muscle inserts into the anteromedial humerus in the “bicip-
ital groove.” The nervous innervation is via branches of the
lateral and medial pectoral nerves. Motoneurons at the C5
and C6 levels innervate the clavicular head, and motoneurons
at the C7, C8, and T1 levels innervate the sternocostal head.
The muscle’s main action is adduction and medial rotation of
the humerus, but it also has complex actions on the scapula.
The breathing-related role of the pectoralis muscles has
not been studied extensively, but a few technically ingenious
studies have been done. Criner et al. (91) stimulated the deep
pectoral muscles in supine, anesthetized dogs while measur-
ing the change in esophageal pressure, which is a commonly
used index of rib cage expansion or contraction. Rib cage
expansion is associated with a negative change in esophageal
pressure (i.e., below atmospheric pressure), while thoracic
contraction is associated with more positive esophageal pres-
sures. During bilateral stimulation of the deep pectoral mus-
cles, the esophageal pressure fell, and lung volume increased,
consistent with an inspiratory action. However, this was
observed only when each animal’s forelimbs were elevated
above the head. When the forelimbs were at the animal’s side,
stimulation of the pectoral muscles caused a positive swing
in esophageal pressure, consistent with compression of the
rib cage, and an expiratory action of the pectoralis muscles.
Apparently, changing forelimb position changed the angle
between pectoral muscle fibers and the sternum, which altered
the muscle’s length and mechanical action on the rib cage, and
substantially changed the size and direction of the thoracic
movement associated with muscle contraction. Though it is
unclear whether the stimulation described above activated the
pectoralis major, minor, or both, these fascinating observa-
tions show that the pectoral muscles can play a role in breath-
ing at least under some conditions. Breathing-related EMG
activities of the pectoralis major muscles have also been stud-
ied in healthy human subjects, as shown in Figure 11I (66).
The tracings in the left-hand panels were recorded as the sub-
ject made an inspiratory effort at 80% vital capacity against
an occluded airway (absence of inspiratory flow and tidal vol-
ume), showing marked recruitment of the pectoralis major.
1061
The Muscles of Breathing
No activity was observed during eupnea, but a small amount
of activity was observed when subjects breathed against a
large inspiratory resistance, as shown in the right-hand panels
of Figure 11I. These studies in dogs and humans indicate that
the pectoral muscles can contribute to breathing, but investi-
gations are few and more detailed studies are needed.
The serratus anterior muscle originates on the first eight
or nine ribs. While most ribs have one sheet of muscle, in
some instances two sheets of muscle can be observed. The
insertion points include the medial border of the scapula and
the thoracic vertebrae (Fig. 11B). Anatomists often describe
three parts of the muscle, but all three parts serve to protract
(extend and pull forward) and stabilize the scapula, which
supports forward reaching with the arms. The innervation is
via the thoracic nerve (“Bell’s nerve”), which is a branch
of the brachial plexus, and the motor neurons are located in
cervical segments 5-7.
Whether the serratus anterior muscles have a breathing-
related function is not clear. However, when the shoulder
girdle is fixed, activation of the serratus muscles elevates the
ribs and expands the thorax, suggesting an inspiratory func-
tion. Reid et al. (356) recorded the serratus anterior EMG in
30 healthy human subjects (15 males and 15 females) aged
5 to 62 years. They did not report any eupneic activity, but
voluntary deep breathing efforts recruited the muscle in all
subjects. The recruitment threshold averaged 61% of the vital
capacity when subjects were standing and 35% when subjects
were seated and leaning forward with the elbows supported
on a table (Fig. 11J). The activity was mainly inspiratory,
but some subjects showed early expiratory activity as well.
The authors suggest that the muscle is an important acces-
sory inspiratory muscle, especially under conditions when the
muscle is placed at optimal mechanical advantage for rib cage
expansion. Recruitment of the serratus anterior muscle was
confirmed in another study showing clear EMG activity dur-
ing maximal volitional inspiratory efforts in healthy human
subjects, consistent with an inspiratory assist function under
conditions of high ventilatory drive (73). Interestingly, after
a 200-meter swim at 90% of race pace, the median frequency
of the serratus anterior EMG fell by 11%, and the fall in EMG
was correlated with the drop in both breathing frequency and
stroke rate of swimming (280). Thus, it is unclear whether
the changes in EMG activity reflect the muscle’s action in
swimming, breathing or both. In another study, serratus ante-
rior oxygenation (measured via near infrared spectroscopy)
began to fall when subjects reached about 85% of their
maximal exercise capacity, which the authors suggest was
the result of increased recruitment of the muscle under these
conditions (274). However, the muscle was not activated dur-
ing seated cycle ergometry when the arms were held folded
and relaxed (68). In sum, the serratus anterior appears to play
a role in inspiratory expansion of the rib cage under condi-
tions of very high respiratory drive, with posture playing an
important modulatory role.
The subclavius and subcostalis muscles may play a role
in breathing, but this has not been evaluated. The former is
1062
Comprehensive Physiology
a small triangular muscle that originates on each of the first
ribs, adjacent to the costoclavicular ligament, and inserts on
the caudal surface of the clavicle. The subclavian nerve, which
is a branch of the fifth and sixth cervical nerves, innervates
the muscle and the motoneurons are found at cervical levels
C5 and C6. Contraction of the subclavius helps to depress
the shoulder and clavicle, but it can also elevate the first rib,
thereby assisting thoracic expansion and serving a respiratory
function. The subcostalis is a very thin sheet of muscle in
the innermost part of the intercostal muscle group, along with
triangularis sterni. It is often missing in the upper intercostal
spaces, but is typically obvious in the lower spaces. The mus-
cle originates on the inner surface of a rostral rib and inserts
into the inner surface of a caudal rib that is often two to three
ribs below the rib of origin. As with the triangularis sterni, fine
branches of the intercostal nerve innervate the muscle, though
it is not clear if innervation is from the nerve associated with
the rib of origin, from the ribs below the point of origin, or
from both. The fiber orientation of the subcostalis is similar
to that of the triangularis sterni and internal intercostal mus-
cles, and its action is to depress the ribs, which would reduce
thoracic volume and promote expiratory gas flow.
Interestingly, the C5 segment of the spinal cord contains
motor neurons innervating all thoracic muscles just discussed
as well as phrenic motoneurons. From a spinal cord injury
perspective, it is important to determine which thoracic mus-
cles retain breathing-related activity, as those muscles can be
the focus of rehabilitative efforts that, in some cases, could
reduce the need for mechanical ventilation.
Abdominal muscles
This group of muscles includes the diaphragm (Fig. 12A),
and the, external and internal obliques, rectus abdomi-
nis, transversus abdominis and the quadratus lumborum
(Fig. 12A12C). With the exception of the diaphragm and
quadratus lumborum, which are active during inspiration, the
abdominal muscles are activated during the expiratory phase.
In healthy subjects, they are quiet in eupnea but recruited
when respiratory drive increases. Abdominal expiratory
muscle contractions reduce thoracic volume and promote
expiratory gas flow, so they are clearly expiratory muscles.
Abdominal muscle contraction on expiration can also assist
the diaphragm by lengthening its fibers and thus placing the
diaphragm on a more favorable position on its length-tension
relation thereby increasing mechanical efficiency (357, 370).
The anterior abdominal muscles (i.e., all muscles except the
quadratus lumborum and diaphragm) are also involved in
trunk rotation and other postural maneuvers, and participate
importantly in expulsive maneuvers including cough, vom-
iting, and childbirth [reviewed in (233)]. We first describe
the basic anatomy of each muscle, and then address their
breathing-related activation.
The diaphragm muscle is unique to mammals, and infor-
mation on its evolution and complex mechanical actions is
reviewed in several excellent articles (114, 208, 342), so here
Volume 9, July 2019
Comprehensive Physiology
we give only a brief summary. These reviews advance the idea
that reptiles, which lack a diaphragm, possess a high compli-
ance, low surface area lung, and the diaphragm evolved to
inflate a low compliance, high surface area mammalian lung
without a large increase in the work of breathing, thereby
providing mammals with a much greater aerobic capacity.
The diaphragm is active with virtually every breath under all
conditions in mammals, and it is, for this reason, considered
the primary inspiratory muscle. The diaphragm muscle fibers
originate circumferentially along the internal body wall on
lumbar vertebrae, ribs, and the sternum and insert into the
flat central tendon. The diaphragm separates the thorax from
the abdomen and forms the “floor” of the thorax in upright
humans. The diaphragm has two main functional parts, the
costal and crural regions. The costal diaphragm is anatom-
ically defined to encompass the fibers that originate on the
inner surface of the lower six costal cartilages, the lower four
ribs and the xiphoid process of the sternum, with the insertion
point the anterior and lateral regions of the central tendon.
The fibers that originate from the lower ribs are more or less
vertically aligned, forming what has been called a “zone of
apposition” between muscle and ribs (281). This zone effec-
tively “seals off” the lower ribs from the pressure changes
in the pleural space (281). Instead, the lower ribs are sub-
jected to abdominal pressure, and as a result, the transmural
pressure across the lower ribs is abdominal pressure minus
atmospheric pressure. Since abdominal pressure rises as the
diaphragm descends during inspiration, transmural pressure
increases, and the thorax expands along its rostral-caudal axis,
and the lower ribs are also displaced laterally, causing further
thoracic expansion (114). Thus, the costal diaphragm con-
tributes to expansion of the thorax by displacing the abdomen
anteriorly and caudally and displacing the lower ribs laterally
and outward. The crural diaphragm originates largely on the
lumbar spine and the aponeurotic arcuate ligaments, and has
a foramen through which the esophagus and aorta pass, while
the vena cava passes through a foramen in the central tendon.
Isolated stimulation of the crural diaphragm also increases
abdominal pressure and dimensions, but does not expand the
rib cage (114). These observations suggest that the two parts
of the diaphragm are both anatomically and functionally dis-
tinct, consistent with their different embryologic origins (243)
and that the crural diaphragm is devoted mainly to digestive
functions (346).
Phrenic motoneurons innervate the diaphragm, and in
most species, they are located in spinal cord segments C3
through C6 (465). The axons of phrenic motoneurons emerge
from cervical ventral roots C3, C4, and C5, where they join
together to form the phrenic nerves, which descend bilaterally
to the upper dome of the diaphragm, more or less lateral to the
great veins and pericardium. The phrenic motoneurons receive
descending input from medullary pre-motoneurons in the dor-
sal and ventral respiratory groups, with significant species
variation. In the rat, about 80% of the phrenic premotor neu-
rons are in the ventral respiratory group (127), and about half
the premotor neurons project ipsilaterally and half project
Volume 9, July 2019
The Muscles of Breathing
contralaterally; only about 4% of the premotor neurons are
located in the nucleus of the solitary tract (NTS). In contrast,
cats appear to have a larger proportion of phrenic premotor
neurons in the NTS, though there is some disagreement among
studies (86, 414, 418). In humans, cats, and dogs the axons
of premotoneurons innervating the diaphragm mostly cross
before descending in the spinal cord, where they make mostly
monosynaptic connections with the phrenic motoneurons.
There is no doubt that the diaphragm is active during each
breath in all mammals, including humans. Moreover, given
that diaphragm EMG activity has been recorded in multiple
studies and in many species (for a recent review, see (65),
we will not overelaborate. The diaphragm is active through-
out the inspiratory period and continues to discharge into the
early expiratory period (Fig. 11B). The early expiratory activ-
ity is typically called “post-inspiration inspiratory activity,”
and its putative function is to counteract lung elastic recoil
pressure so that the lungs do not deflate too quickly and/or
too completely. Neural drive to the diaphragm also increases
during central and peripheral chemoreceptor stimulation and
exercise, so that the diaphragm plays a major role in the aug-
mentation of pulmonary ventilation that occurs under these
conditions.
The thin, quadrilateral external oblique muscle is situated
on the lateral and anterior parts of the abdomen and consists of
eight bundles that originate on the inferior margins of the fifth
through twelfth ribs (Fig. 12C). The bundles take different
routes to their insertion points; those arising from the lower
ribs plunging vertically downward to insert into the ante-
rior region of the iliac crest. The remaining fibers descend
more obliquely and form an aponeurosis, which terminates
at the midline linea alba. The external oblique muscles are
innervated by motoneurons in the lower two or three thoracic
segments, and the upper three lumbar segments. In addition
to flexion and rotation of the vertebral column, contraction
of the external oblique muscles displaces the thorax caudally
and raises intra-abdominal pressure, actions that reflect the
expiratory function of these muscles.
The internal oblique muscle lies just below the external
oblique, and its fibers are aligned perpendicularly to the exter-
nal oblique fibers (Fig. 12C). The fibers originate on the iliac
crest, the thoracolumbar fascia of the lower back, and from
the inguinal ligament. The fibers travel obliquely upward to
insert on ribs 10 to 12 and into the linea alba. The innerva-
tion is by lumbar motoneurons, with the majority in lumbar
segments 1 to 3. When activated, the internal obliques com-
press the abdominal wall, which displaces the diaphragm cra-
nially, thereby reducing the size of the thorax and facilitating
exhalation. The muscle is also involved in rotating the thorax
toward the hips and lower back on the same side.
The transversus abdominis muscle lies deep to the inter-
nal oblique muscles, just above the peritoneum. Fibers of the
transversus abdominis originate on the inguinal ligament, the
iliac crest and the cartilaginous portion of the lower six ribs.
The lower fibers insert into the pubic crest, and the remaining
fibers into the linea alba (Fig. 12C). Like the internal oblique,
1063
The Muscles of Breathing Comprehensive Physiology

(A) (C)

External
Left Transversus oblique
abdominis Quadratus
Right dome lumborum
Rectus
dome abdominis
Internal
oblique

Right crus Left crus (D) A

Volume 1L
(B) Abdomen AP
EMG RA
Diaphragm
EMG EO
EMG TA
EMG 1s
B
1L

30
Hz 1s
C
0 1L

2 I

(E)
1s
(G)
Rectus
Extern B

Intern
A
Transv
(L/s)
1 100 ms
Flow 0
–1
5 4 3 2 1
Volume 1 (L)
1s

(F)
Rest 100 Watts 200 Watts 350 Watts
EMG RA

EMG EO

P mouth
5s 2s 2s 2s
Unoccluded maximal exhalation

EMG RA

EMG EO

5s

1064 Volume 9, July 2019

Comprehensive Physiology The Muscles of Breathing

the transversus abdominis also compresses the abdomen and
draws the lower ribs medially, making it a powerful expi-
ratory muscle. Innervation is via thoracoabdominal nerves
(T6-T11), the subcostal nerves (T12), and the ilioinguinal
and iliohypogastric branches of L1.
The fibers of the rectus abdominis muscles are oriented
vertically, and left and right muscles are parallel to one another
and separated by the linea alba (Fig. 12C). The muscle is con-
tained in the rectus sheath within dense bands of connective
tissue (“the tendinous intersections”) that divide the muscle
into three bellies on each side. The muscle fibers originate on
the xiphoid process of the sternum and on the costal cartilages
of the fifth to eighth ribs and insert into the pubic bone. Inner-
vation is by motor nerves of the sixth to eleventh intercostal
nerves. In addition to playing an important role in flexion
of the lumbar spine, contraction also raises intra-abdominal
pressure, which helps accelerate expiratory airflow.
The quadratus lumborum is the only posterior abdominal
muscle, and it is often considered a back muscle. It is a deep
muscle, is more or less four sided, and is wider caudally than
rostrally (Fig. 12C). The fibers originate on the iliac crest
and ilioloumbar ligament and ascend to insert on the inferior
border of the lower-most rib on each side. It also has four
small, medial fiber bundles, each terminating in a tendon, and
each tendon in turn inserts onto one of the upper four lumbar
vertebrae. The twelfth thoracic and upper four lumbar motor
nerves innervate the muscle.
Activation of abdominal expiratory muscles by lung infla-
tion, hypercapnia and hypoxia have been well-documented
in anesthetized, decerebrate, and awake animal models, and
eupneic activity is reported in some studies, but not all
[reviewed in (233)]. Studies in human subjects reveal some
eupneic activity in the standing posture, but minimal to none
in supine subjects. The transversus abdominis appears to
have the greatest respiratory-related activity, followed by
the internal oblique, external oblique, and rectus abdomi-
nis (2, 105, 432). There are some differences, however. For
example, Figure 12D shows recruitment of the transversus
abdominis, but not external oblique or rectus abdominis, dur-
ing moderate hypercapnia. When the hypercapnia became
more severe (end-tidal PCO2 50 mmHg), transversus activ-
ity increased further and recruitment of the rectus abdominis
was observed, but no clear activity emerged in the exter-
nal oblique (105). However, another study in human subjects
showed that with even more severe hypercapnia (end-tidal
PCO2 63 mmHg), all four abdominal muscles were recruited
(Fig. 12E) (2). Moreover, it is clear in these recordings that
expiratory activity begins in mid-to-late expiration, increases
in intensity throughout the expiratory period, and contin-
ues into early inspiration before it terminates rather abruptly.
These observations are consistent with an inspiratory assist
function of the abdominal muscles in addition to their primary
role in accelerating expiratory airflow, as discussed earlier.
These observations under conditions of chemoreceptor stimu-
lation are generally consistent with observations made during
exercise in young healthy subjects. As shown in Figure 12F,
there was no rectus abdominis or external oblique activity dur-
ing resting breathing in young subjects seated on a bicycle (3).
However, as the exercise intensity increased progressively, the
external oblique was recruited at a workload of 100 watts, with
a monotonic rise in activity as intensity continued to increase,
up to 350 W. In contrast, the rectus abdominis was activated
only during very intense exercise (350 W). Thus, respiration-
related activation of human abdominal expiratory muscles is
evoked by chemoreceptor stimulation and exercise, though
the recruitment thresholds of each of the abdominal muscles
can differ widely. The recruitment threshold likely depends
on the type of stimulus, posture, and the compliance of the
abdominal and chest wall, among other factors.
Contraction of the quadratus lumborum (Fig. 12C) fixes
the last rib and stabilizes the lumbar vertebrae. Because the
posterior fibers of the diaphragm also insert into the upper
lumbar vertebrae, such fixation allows the diaphragm to gen-
erate more force. As such, the quadratus lumborum could
be considered an accessory inspiratory muscle. Figure 12G
shows EMG recordings of the quadratus lumborum (upper
trace) and diaphragm (lower trace) in an anesthetized rabbit
(47). The numbers below the tracings indicate different phases
of the respiratory cycle, with phase 2 demarcating inspira-
tion. It is clear that the quadratus is active during inspiration,


Figure 12 The abdominal muscles. Panels A and C illustrate the diaphragm and abdominal muscles, respectively. Panel B shows the diaphragm
EMG (top trace), the moving time averaged EMG, and a raster plot show the discharge frequency of the large motor unit that is visible in the EMG
recording. The bottom trace is tidal volume and inspiration is upward. Note that the commonly observed inspiratory, augmenting discharge pattern
of the diaphragm EMG is the result of a rapid rise in discharge frequency at inspiratory onset, followed by a plateau near the middle and end
of the inspiratory period (379). Panel D shows three sets of recordings, and in each set (from top down), lung volume (inspiration upward), the
anterior-posterior dimensions of the abdomen, and EMG recordings from rectus abdominis (RA), external oblique (EO), and transversus abdominis
(TA) muscles. Recordings were made in a young healthy male subject studied while sitting upright. The upper, middle, and lower sets of tracings were
recorded during quiet breathing (end-tidal CO2 = 42 mmHg), and two levels of hypercapnia (end-tidal CO2 = 46 and 50 mmHg). Note that only the
transversus was active during quiet breathing, and the other two muscles were not recruited until the end-tidal CO2 was 50 mmHg (105). Panel E
shows EMG recordings from each of the four anterior abdominal muscles, during severe hypercapnia (end-tidal CO2 = 63 mmHg) in a young,
healthy supine subject. Inspiration is represented by upward deflections in both flow and volume recordings (2). Panel F shows intramuscular EMG
recordings from the rectus abdominis (RA) and external oblique abdominal muscles, and mouth pressure at rest and during progressive intensity,
cycle ergometer exercise in a young, fit cyclist. In this study, the EO was recruited in light exercise, but the RA was recruited only during very heavy
exercise. The EMG activities obtained during a maximal voluntary expiration against an occluded airway are shown in the bottom of the panel
(3). Panel E shows representative EMG recordings of the quadratus lumborum (upper trace) and the diaphragm (lower trace) from an anesthetized
rabbit during quiet breathing. The numbers represent different phases of the respiratory cycle: from left to right, expiration (5), preexpiration (4),
end of inspiration (3), inspiration (2), and preinspiration (1). Activity is almost exclusively inspiratory, indicating that the quadratus lumborum is an
accessory inspiratory muscle.

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The Muscles of Breathing
consistent with its role as an accessory inspiratory muscle.
We are unaware of studies of this muscle in human subjects,
at least where respiration-related activity was the principle
focus. There are some observations where quadratus activity
during trunk rotations appeared to be slightly higher during
inspiration than expiration (337), consistent with the muscle’s
role as an accessory inspiratory muscle.
Back Muscles
This category includes the “erector spinae,” which is a group
of muscles (see below); the latissimus dorsi; the levatores
costarum; rhomboid major and minor; serratus posterior infe-
rior; serratus posterior superior; and the levator scapulae. We
categorized the trapezius as a head and neck muscle, and
its breathing-related behavior was considered above. To the
best of our knowledge, the only back muscles that have been
studied in the context of the control of breathing are the lev-
atores costarum muscles (or simply the “levator costae”), the
latissimus dorsi, and the iliocostalis lumborum of the erector
spinae group.
The levator costae originate bilaterally on the transverse
processes of the seventh cervical through eleventh thoracic
vertebrae (Fig. 12B). The muscles insert onto the caudal most
rib with fibers orientated downward and lateral, in parallel
with the external intercostal muscle fibers. The four most
caudal levator costae usually divide into two bundles, one of
which inserts two ribs below its point of origin. The muscles
are innervated by fine dorsal rami of spinal nerves from cervi-
cal 8 through thoracic 11 levels. Contraction elevates the ribs
and expands the rib cage, thus assisting inspiration. Several
experiments, many published by DeTroyer and colleagues in
animal models, describe recruitment of levator costae mus-
cles in phase with inspiration. Anesthetized dogs show clear,
phasic inspiratory activity during eupnea in the supine pos-
ture, as shown in Figure 11C (108), though a motor unit with
a tonic discharge pattern can also be observed. Denervation
of the parasternal intercostals bilaterally caused hypoventila-
tion and recruitment of the levator costae muscles, due to a
hypoventilation-mediated rise in PaCO2 , spinal reflexes from
muscle spindles in adjacent intercostal muscles (115), and
reflexes originating from pulmonary stretch receptors (100).
Additional experiments, also in anesthetized dogs, indi-
cated that levator costae muscles in rostral intercostal spaces
were active during inspiration, and the activity rose when
resistance to inspiration was increased by reducing the
diameter of the tracheostomy tubing. Interestingly, the more
caudal levator costae muscles rarely showed activity in quiet
breathing, and activity could not be evoked even when airflow
resistance was increased (101). In the rat, EMG recordings of
the levator costae attached to the tenth rib showed phasic
inspiratory activity during eupnea, with a doubling of activ-
ity after phrenic nerve transection (400). Similarly, there was
consistent, phasic inspiration-related discharge in the levator
costae in supine, anesthetized baboons (107). Data in a single
human subject studied in the standing position demonstrated
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Comprehensive Physiology
inspiratory EMG activity in levator costae muscles from the
ninth and tenth thoracic interspaces during quiet breathing,
though phasic inspiratory activity was often accompanied
by tonic activation of the levator costae with changes in
posture (169). Studies in anesthetized cats suggest that the
EMG recordings were truly from the levator costae muscles,
and not the result of contamination from adjacent intercostal
muscles; the studies showed that levator costae motoneurons
receive both inspiratory-related, descending excitatory synap-
tic potentials, as well as afferent inputs from muscle spindles
and tendon organs (206).
The large, flat latissimus dorsi originates on the spinous
processes of the T7 to L5 vertebrae, as well as from the thora-
columbar fascia, the iliac crest, the bottom four ribs, and the
inferior angle of the scapula. It inserts into the intertubercular
groove of the humerus. It is innervated by the thoracodorsal, or
“long scapular nerve,” which itself is composed of branches
of the sixth, seventh and eighth cervical nerves. The main
actions of the muscle include extension and internal rotation
of the arm, and trunk rotation. As shown in Figure 13D, the
human latissimus dorsi muscle is recruited during inspiratory
efforts to 80% of vital capacity (left-hand panels) and during
breathing against an inspiratory resistive load (right-hand pan-
els) (66). Orozco-Levi et al. (334) also recorded inspiratory
activity from the human latissimus dorsi: there was minimal
activity at baseline (1.8% of that recorded during a maxi-
mal activation evoked by forced adduction of the arm), but
progressively increasing activity when breathing against an
inspiratory resistive load. The activity recorded at the highest
inspiratory load averaged about 32% of the maximal voli-
tional force in 11 subjects. Gutierrez et al. (182) also reported
inspiratory-related activity of latissimus dorsi during eupnea,
though the activity was not quantified. Observations in sub-
jects with and without spinal cord injury showed increased
latissimus dorsi activity during a forced expiratory maneuver,
which suggests that the muscle may play a role in expiration
as well as inspiration (435).
The erector spinae muscles originate from a thick tendon
that is attached on the sacral crest and from the spinous pro-
cesses of the eleventh and twelfth thoracic vertebrae, and
each of the lumbar vertebrae. The erector spinae muscle
group is has three main parts, each with three subcomponents
(Fig. 13B): the iliocostalis laterally, composed of the ilio-
costalis lumborum, thoracis, and cervicis; the longissimus,
which is the middle of the three muscles and consists of the
longissimus thoracis, cervices, and capitis; and the medial
spinalis, which consists of the spinalis thoracis, cervices, and
capitis. The insertion points of these muscles are widespread,
but in the context of breathing, the important attachments
are to the posterior portion of ribs 3 to 12. The muscles are
supplied by lower cervical, thoracic, and upper lumbar spinal
nerves. The main action of these muscles is extension of the
vertebral column, though they also play a role in lateral flexion
of the spine.
Cala et al. (66) recorded the EMG in erector spinae
muscles adjacent to the T6 and T7 vertebral space, which
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Comprehensive Physiology The Muscles of Breathing

(A) (B) (C)

Levator
Trapezius scapulae 200 mL
Volume
Rhomboid
minor Spinalis
Rhomboid (thoracic only) Parasternal
major
Longissimus
Latissimus Levator External
dorsi costae
intercostal
Iliocostalis

Levator
costae
2s

(D) (E)
A B
Mouth pressure
25
(cmH2O) 40 Inspiration
EMG, 10th intercostal
Inspiratory 0.5 0.5 space
flow (L/s)

EMG, Iliocostalis
Tidal volume 4.0 1.0 lumborum
(L)

Erector spinae
iEMG

Latissimus dorsi
iEMG
Trapezius
iEMG
15 s

Figure 13 The back muscles. Panels A and B illustrate the superficial (A) and deep back muscles (B), as described in the text. Panel C shows
lung volume and intercostal muscle EMG recordings in an anesthetized, supine dog breathing quietly. Note that the levator costae, as well
as the more commonly studied intercostal muscles, are phasically active during inspiration; adapted, with permission, from (108). Panel D
shows (from top down) representative recordings of mouth pressure, inspiratory flow, tidal volume, and the moving-time averaged EMG of
an erector spinae muscle, the latissimus dorsi, and the trapezius in a young, healthy subject. In the left-hand panels, the subject was asked
to make an inspiratory effort at 80% vital capacity against an occluded airway, while in the right-hand panels the subject breathed against
a large inspiratory resistance (66). Activity was inspiratory in all three muscles. Panel E shows simultaneous recordings from intercostal and
iliocostalis lumborum muscles in a male subject with respiratory myoclonus. Note that both muscles were activated during inspiration. The
small, high-frequency bursts observed in the expiratory period (arrows) confirm the myoclonus (237).

suggests that the recorded activity reflected the action of the
medially located spinalis, though this is not certain. Nonethe-
less, the muscle behaved similarly to the latissimus dorsi;
activity increased during volitional efforts and when breath-
ing against an inspiratory resistance (Fig. 13D). Jinnai et al.
(237) recorded from the iliocostalis lumborum in a single
subject with respiratory myoclonus, and reported rhythmic
inspiratory activity, confirming that these small back muscles
can assist inspiration, at least under some conditions.
Patterns of muscle activity
As described above, the number, discharge patterns, mechan-
ical actions, and interactions of respiratory muscles that are
active at any point in time are complex. Nevertheless, certain
general principles emerge. The general principles governing
the recruitment of respiratory muscles have been reviewed
extensively by others (134, 153, 212, 215, 216, 331, 333, 442),
and they will be summarized only briefly here.
Motor unit recruitment patterns
Greater muscle force may be generated by increasing the
frequency of activation of motor units or by increasing the
number of motor units activated in any given muscle. There is
a well-established size principle in which motor units are acti-
vated as a function of motor neuron size so that smaller neu-
rons, which activate smaller motor units, are activated first (the
smaller a neuron, the greater its excitability for any level of
synaptic input because the small size of the neuron translates
into greater input resistance) (201, 202). Therefore, muscle
force increases smoothly as the firing frequency of individ-
ual motor units is increased to the point of tetany and larger
and larger motor units are activated. Muscles that generate

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gross movements tend to have larger motor units (for exam-
ple, limb muscles generating large forceful movements and
the muscles of posture), and muscles that are responsible
for fine motor control tend to have smaller motor units (the
muscles of the eye and hand, for example). Beyond the size
principle, it seems that motor neurons serving an individual
muscle receive input from a common source; the central ner-
vous system controls the balance of excitatory and inhibitory
inputs to the motor neuron pool so that all neurons in that
pool receive the same drive (99, 312, 364). This is efficient
in terms of optimal central control of motor activity, and the
pattern of activation of individual motor units may still vary
because even with a common drive, individual motor neu-
rons activating motor units within the same muscle will be
more or less susceptible to activation depending on the size
of the motor neuron and differences in segmental synaptic
inputs. Respiratory muscles show this same orderly pattern of
activation (35, 121, 238, 442). A further subtlety of this order
of activation is that smaller motor units tend to be activated
more frequently, and smaller motor units are more likely to be
fatigue resistant; whereas larger motor units, which are acti-
vated less frequently and only for short durations during larger
respiratory efforts, tend to be less fatigue resistant (121, 405).
In muscles innervated by the hypoglossal nerve (e.g., the
genioglossus), increasing respiratory drive leads mainly to
increased recruitment of additional motor units (239,314,366)
rather than an increase in the rate of firing of individual motor
units. Moreover, as respiratory drive increases, the inspira-
tory modulated motor units, those with both tonic and phasic
inspiratory activity, respond to increases in respiratory drive
by recruiting additional motor units; whereas the expiratory
modulated units within the upper airway muscles studied are
less sensitive to increasing respiratory drive and more prone
to demonstrate modulation of muscle force by changes in
motor unit discharge rates (442, 462, 476). This has led to
the hypothesis that upper airway muscles with phasic inspi-
ratory activity increase force by recruiting additional motor
units and this phasic inspiratory activity generates the gross,
respiratory-related movements of upper airway muscles. In
contrast, the activity of expiratory and the purely tonic motor
units is modulated by variation in the frequency of motor unit
discharge, which is used to fine tune the actions of upper
airway muscles in response to reflex mechanisms reflecting
the local conditions in which each upper airway muscle oper-
ates (442).
Finally, all muscles are activated in ways that are mechan-
ically advantageous. This has been particularly well studied
in intercostal muscles where the order of activation of inter-
costal muscles proceeds from the rostral intercostal spaces to
the caudal interspaces as the mechanical advantage of each
intercostal space is optimal (110,271). Activation of the mus-
cles is also graded along the mediolateral axis; medial activa-
tion is greater and occurs earlier and lateral activation is less
(if it occurs at all) and later in the parasternal muscle (111).
Moreover, the rostral external intercostal muscles, which are
activated more, are also more resistant to fatigue compared
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Comprehensive Physiology
to more caudal intercostal fibers (193), and those intercostal
muscles that are most intensely activated, muscles with inspi-
ratory activity, also have a greater representation of fatigue
resistant fibers (177).
Respiratory muscle activity during sleep
The activity of respiratory muscles is acutely tuned to not
only the metabolic demands of the organism, but behavioral
demands as well. Of interest here is that three stages of behav-
ioral arousal have been defined in which respiratory drive
and therefore respiratory muscle activity changes dramati-
cally and in characteristic ways: wakefulness, non-rapid eye
movement (NREM) sleep, and rapid eye movement (REM)
sleep. These states are defined phenomenologically largely
on the basis of patterns of electroencephalographic activity,
muscle activities and externally observable behaviors (respon-
sive or non-responsive to commands, eyes open or closed,
etc.). A network of reciprocally connected neural groups in
the hypothalamus and brainstem regulate the occurrence and
interplay of these behavioral states (386), and this neuronal
network interacts with and modulates the activity of the respi-
ratory control system within the brainstem to change the level
of respiratory muscle activity as a function of behavioral state
(214). Within each behavioral state, there are further subdi-
visions based on subtle variations in the EEG. For example,
NREM sleep is divided into four stages in which the fre-
quency of the EEG diminishes and the amplitude increases,
and these stages seem to correspond to increasingly deep
states of NREM sleep, and REM sleep is distinguished by
both phasic and tonic episodes. Hence, REM sleep, NREM
sleep, and wakefulness are not unitary states, and respiratory
muscle activity varies, as a consequence, even within each
state—especially during the wide range of possible activities
during wakefulness.
The diversity of muscles recruited to support the demands
of breathing is greatest during wakefulness as befits the wide
range of activities humans pursue during their daily lives (27).
Therefore, those muscles that are recruited to augment res-
piration only during the most extreme respiratory maneuvers
(maximal inspiratory and expiratory activities, respiration in
contorted positions and exercise) are active only during wake-
fulness. During NREM sleep, metabolic demand is reduced,
and the central nervous system actively ignores external sen-
sory inputs so that the diversity of behavioral, sensory and
brain-derived inputs supporting respiratory drive are reduced
largely to the chemical control of ventilation (oxygen and
carbon dioxide levels), and reflex regulation of respiratory
function seems to be reduced. For example, the Hering-Breuer
reflex appears to be blunted during sleep (111), and load com-
pensation is diminished (96, 199). The inspiratory activity of
the diaphragm persists, and the inspiratory activity of muscles
of the chest wall and the upper way remains during NREM
sleep, but at a reduced level (315, 442, 474), likely commen-
surate with the reduction in behavioral and waking inputs
that drive respiratory activity. The muscles that augment
Volume 9, July 2019
Comprehensive Physiology
respiration only when respiratory drive is high, or during
volitional tasks that require the generation of large respiratory
muscle forces, are inactive during NREM sleep. For example,
postural muscles in the back or shoulder girdle, which may
have a respiratory function during maximal voluntary inspira-
tion, are usually inactive during NREM sleep. When supine,
the weight of abdominal contents loads the diaphragm and
reduced drive to the muscles of the upper airway increases
upper airway resistance. Load compensating reflexes are less
sensitive or less effective during sleep, and pulmonary venti-
lation is reduced during NREM sleep. The reduction in ven-
tilation reflects both a true reduction in respiratory muscle
activation, and a further reduction in airflow imposed by the
increased flow resistance of the upper airway (200), and the
reduction in chest wall stiffness associated with reduced inspi-
ratory intercostal activity (369). During REM sleep there is a
further reduction in the tonic drive to respiratory muscles of
the thorax and upper airway. The activity of the diaphragm, on
the other hand, is less susceptible to inhibition during REM
sleep and remains persistently active, which may reflect the
paucity of muscle spindles in the diaphragm compared to
other respiratory-related muscles (132). The loss of respira-
tory drive to the intercostal and upper airway muscles during
NREM and REM sleep makes breathing less stable and vul-
nerable to disruption during these sleep states.
The drive to respiratory muscles originates from multiple
sources: volitional and unconscious motor commands occur
throughout multiple behaviors. There are, in addition, reflex
mechanisms that provide constant feedback about the effec-
tiveness (or not) of particular actions and modify the motor
command to ensure completion of the motor task; and there
is a drive to respiratory muscles associated with the waking
state – known as the waking stimulus (145, 146). The wak-
ing stimulus is thought to originate from multiple sources
that bombard the central nervous system during wakefulness.
There are three primary sources, including: sensory stimula-
tion generated by both external and internal sources associated
with the pursuit of the wide variety of behaviors associated
with wakefulness; the reticular activating system, which pro-
vides a large, internally generated source of neural drive that
sustains respiratory muscle activity during wakefulness and
diminishes during sleep; and a variety of excitatory neuro-
transmitter systems that are more active during wakefulness
than during sleep (332). Originally, the focus was on state-
related serotonergic and noradrenergic inputs to motor neu-
rons, which are ubiquitous in wakefulness but wane during
NREM sleep and virtually disappear during REM sleep (332).
However, as the waking stimulus has been studied further, our
knowledge of the number and complexity of neurotransmitter
systems that contribute to state-related, waking enhancement
of motor neuron function has grown. This is particularly true
of motor neurons innervating upper airway muscles, where
there is now evidence for excitatory glutamatergic, histamin-
ergic, and cholinergic inputs in addition to the serotonergic
and noradrenergic inputs (all of which decline during NREM
sleep and decline further or cease altogether in REM sleep).
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The Muscles of Breathing
There is also evidence of inhibitory GABAergic inputs to
upper airway motor neurons during wakefulness, especially
at end-inspiration, and this inhibitory input increases further
during sleep (213). Not all of these neurotransmitter sys-
tems are active tonically, for example, histamine (31), and
the importance attributed to serotonin as part of the waking
stimulus has actually diminished as more intact, freely mov-
ing animals have been studied (416). Nevertheless, all of these
neurotransmitters have the capacity to modulate motor neuron
function when behaviorally appropriate (213). For example,
during wakefulness, when these excitatory neurotransmitters
are released, activation of their associated receptors provides
a significant direct and indirect drive to the activity of the
neurons that generate the drive to individual respiratory mus-
cle motor neurons (431). When wakefulness ceases and sleep
begins, the waking stimulus is lost, and the drive to most res-
piratory muscles diminishes as described above (219). The
decline in tonic drive to respiratory motor neurons, which
occurs immediately as NREM sleep begins (478), reflects to
a great extent the loss of behavioral activation of neurons
that actually have a relatively weak relationship to respiratory
muscle activity (331). As a result, the regulation of respiratory
muscle activity during NREM sleep is under the control of the
internal regulatory mechanisms within the brainstem, which
depend largely on the chemical control of ventilation derived
from central and peripheral chemoreceptors (345). During
REM sleep there is a further decline in respiratory muscle
activity (172, 219), and active glycinergic inhibition of mus-
cles of the axial skeleton (78,411,412). In contrast, glycinergic
inhibition of motor neuron activity may play no role or only
a small role in the decline in upper airway muscle activity
during REM sleep (36, 58, 256, 304, 305). It seems that dis-
facilitation of upper airway motor activity, by withdrawal of
excitatory inputs diminishes the activity of upper airway mus-
cles innervated by cranial nerve XII, and there is a contribu-
tion from increased GABAergic inhibition (76,213,416,422),
but the dominant mechanism of REM sleep atonia of upper
airway muscles is likely to depend on a muscarinic, cholin-
ergic mechanism that activates G-protein-coupled inwardly
rectifying potassium (GIRK) channels (172). Activation of
GIRK channels leads to hyperpolarization of hypoglossal and
trigeminal motoneurons and reduces their excitability (216).
This cholinergic input to hypoglossal motor neurons during
REM sleep seems to arise from the intermediate lateral retic-
ular formation, a premotor input that is thought to contribute
to the divergent patterns of hypoglossal motor neuron regu-
lation as compared to the phrenic motor neurons that receive
premotor inputs from the ventral and dorsal bulbospinal neu-
rons (171). In addition to this post-synaptic mechanism, there
may be a presynaptic cholinergic inhibition of glutamatergic
drive to the hypoglossal neurons during REM sleep as well
(32). Respiratory muscle activity during REM sleep seems
to be relatively unaffected by chemical control of ventila-
tion derived from the internal levels of oxygen and carbon
dioxide and dependent instead on internally generated behav-
ioral activity, although the motor activity of these internally
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The Muscles of Breathing
generated behavioral states is actively inhibited, especially
in axial muscles, so that the motor activities associated with
REM sleep and dreaming are not normally acted out (345).
The hierarchy of loss of activation of respiratory mus-
cles as behavioral states change from wakefulness to NREM
sleep to REM sleep seems to be related to the strength of
association of the muscle activity with respiration. This idea
was developed by John Orem (330), and is captured in the
eta-squared statistic, which expresses the extent to which the
timing and magnitude of neuronal activity was correlated with
respiratory activity. It turns out that the NREM sleep-related
decline in activity of respiratory-related neurons is greater
in muscles driven by neurons with low eta-squared values—
low respiratory-relatedness so to speak. Such muscles include
accessory muscles of the shoulder girdle and thorax that may
have a respiratory function during some behaviors, but are not
involved in respiration under the majority of conditions. Mus-
cles innervated by neurons more closely related to respiration
(e.g., muscles of the upper airway with activity tightly cou-
pled to respiration, intercostal muscles and the diaphragm)
are less likely to be inhibited or are inhibited to a lesser extent
during NREM sleep. This implies that respiratory neurons
with greater tonic, nonrespiratory input during wakefulness
are more likely to experience greater declines in activity in the
transition to NREM sleep. During REM sleep, the activity of
respiratory neurons is driven by endogenous inputs from both
nonrespiratory and respiratory sources. The level of nonrespi-
ratory inputs to respiratory motor neurons is variable during
REM sleep and so the activity of respiratory muscles may
be increased or decreased depending on the balance of active
inhibition of the relevant motors neurons and the extent of
excitatory input from nonrespiratory inputs (214, 330).
The timing and amplitude of upper airway muscle
activity: wakefulness vs. sleep
The importance of phasic, respiratory-related upper airway
muscle activity may vary among normal individuals from a
complete absence of phasic genioglossal EMG activity dur-
ing eupnea in normal children with a normal body mass index
(242) to adults with modest phasic upper airway muscle activ-
ity in a variety of upper airway muscles (186, 187, 387, 388)
to quite vigorous phasic activity in patients with OSA dur-
ing wakefulness at rest (470). Thus, the timing and ampli-
tude of upper airway muscle activity is carefully regulated
by central and peripheral reflex mechanisms to maintain
upper airway patency in each individual even as the load
imposed on the respiratory system varies widely. Studies of
vagally mediated lung volume feedback often focus on inspi-
ratory and expiratory timing, which follows from the original
description of the Hering-Breuer reflex (204). However, the
impact of vagal feedback on the timing of inspiration and
expiration is modest, albeit demonstrable, in awake humans
(40, 63, 64, 183, 188, 399), and diminished even further in
sleeping humans (226, 408). On the other hand, vagal feed-
back reflecting lung volume information has a profound effect
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Comprehensive Physiology
on the pattern of activation and inhibition of upper airway
muscles; an effect that is much less apparent in the pattern of
activation of the diaphragm in animals (21, 28, 259, 447). The
function of the Hering-Breuer reflex and lung volume-related
feedback may be less concerned with respiratory timing and
more attentive to the control of respiratory muscle force. Thus,
if lung volume does not increase during a particular breath,
the muscles of the upper airway are activated to a greater
extent than the diaphragm, which is likely meant to relieve
any upper airway obstruction and restore unimpeded volume
expansion of the lung.
Additional reflex mechanisms regulate upper airway mus-
cle activity to maintain upper airway patency, and the activity
of upper airway muscles is modulated by distortions of the
upper airways, the pattern of inspiratory flow, the air tempera-
ture, and the particular phase, inspiration versus expiration, of
the respiratory cycle (153, 255). In tracheostomized patients
with OSA, upper airway tone and upper airway collapsibility
are dependent upon the phase of the respiratory cycle and the
pattern of airflow (392). The critical closing pressure of the
airway was less (more negative, less collapsible) during inspi-
ration compared with expiration, which is consistent with the
decline in upper airway muscle activity that typically occurs
during expiration. In addition, the critical closing pressure
needed to maintain airway patency was reduced (the airway
was less collapsible) during nasal breathing compared with
breathing through the tracheostomy (392). Airflow through
the nose stimulates upper airway muscle activity more effec-
tively than airflow through the mouth in humans (29, 30).
Moreover, upper airway muscle activity is often absent in tra-
cheostomized, anesthetized animals unless airflow is present
in the upper airway (75, 217, 218, 286, 398). Negative pres-
sure within the upper airway profoundly activates muscles of
the upper airway to resist the collapsing pressure. The impor-
tance of upper airway patency to the integrity of respiratory
function means that a variety of reflex mechanisms exist to
maintain airway patency in the face of changes in upper air-
way pressure, flow and temperature, together with changes in
lung volume, airflow in the upper airway, the temperature of
the airway and the lung volume change during ventilation.
Patients with OSA have some combination of anatomi-
cal narrowing or encroachment on the upper airway, usually
associated with increased body weight (327,394), and reduced
activation of upper airway muscles at sleep onset (361, 393,
470). The reflex mechanisms that maintain airway patency
during wakefulness are less effective in patients with OSA
and greater upper airway muscle activity may be necessary
to maintain upper airway patency during wakefulness (242,
294, 326, 429, 470) so that the reserve of muscle activation
is less during sleep at the same time that reflex mechanisms
maintaining airway patency may be reduced. Compounding
this latter problem is evidence of intramuscular neurodegen-
eration in the soft palate and uvula of patients with OSA
(397, 477), and in addition, upper airway sensory afferents
may also degenerate in these patients (154). The neural and
muscular degeneration has been attributed to a combination
Volume 9, July 2019
Comprehensive Physiology
of vibration of upper airway tissue secondary to snoring and
intermittent nocturnal hypoxemia (339). The degeneration
of sensory fibers is consistent with studies demonstrating
reduced respiratory-related evoked potentials during upper
airway stimulation (8, 181, 487) and reduced sensorimotor
function in patients with OSA (133). Thus, altered sensory
function may reduce compensatory upper airway muscle acti-
vation in an anatomical setting in which upper airway muscle
activity is particularly important to keep the airway patent.
In addition to reflex mechanisms modulating the ampli-
tude of respiratory-related activation of upper airway muscles,
it has long been recognized that activation of upper airway
muscles innervated by cranial nerves precedes the activation
of the diaphragm and intercostal muscles. As a result, the
upper airway is dilated and stiffened just before the onset of
inspiratory flow and just before the upper airway is subjected
to transmural pressure gradients that tend to collapse the air-
way. The mechanisms that establish the difference in the time
of onset of upper airway and pump muscles is unknown.
In summary, respiratory muscles fall into three broad
groups. There are nonrespiratory muscles that may assist
respiration when respiratory drive is high, or when large,
volitional respiratory efforts are made. The muscles of the
shoulder girdle and back and some of the muscles of the
face and neck fall into this group. These muscles have a high
threshold for breathing-related recruitment, and their activity
diminishes markedly in NREM sleep. Moreover, spinal motor
neurons—with the exception of the diaphragm—are actively
inhibited by glycinergic mechanisms during REM sleep.
The second group consists of muscles that regularly
participate in breathing but may also serve other functions.
The upper airway and intercostal muscles fall into this group.
Thus, the tongue, for example, is regularly active during
inspiration to help maintain upper airway patency, but the
tongue is also involved in suckling, speech and swallowing.
The reduction in breathing-related activity in these muscles
during NREM sleep tends to be more modest and the loss of
the non-respiratory, behavioral, waking drive to these muscles
is greater—these muscles have a low respiratory-relatedness
as defined by a low eta-squared value. The activity of muscles
in this group that are innervated by cranial nerves also dimin-
ishes during REM sleep, but the mechanism of suppressed
respiratory activity depends on the withdrawal of excitatory
neurotransmitter inputs and the activation of muscarinic
cholinergic mechanisms that hyperpolarize the motor neurons
of these muscles, decrease input resistance and raise the
threshold of synaptic input required to activate these muscles.
The diaphragm is the sole representative of the third group
of muscles. The diaphragm is persistently active in all behav-
ioral states. However, the source of this drive varies as a
function of state: behavioral and metabolic factors modulate
diaphragmatic activity during wakefulness; metabolic factors
modulate diaphragmatic function during NREM sleep as the
waking, behavioral drive to the diaphragm is lost; and endoge-
nously generated behavioral activity drives the diaphragm
during REM sleep without much modulation by metabolic
Volume 9, July 2019
The Muscles of Breathing
control derived from oxygen and carbon dioxide levels. In all
three groups of muscles, the pattern of motor unit recruitment
and the sequencing of muscle activation have evolved to gen-
erate muscle force in a metabolically efficient and mechani-
cally advantageous pattern.
Conclusion
Even before the nervous system has made contact with devel-
oping muscle targets, rhythmic spontaneous neural activity
(rSNA) begins throughout the CNS. rSNA seems to pro-
vide critical signals for developing neural circuits, including
axon pathfinding, synaptogenesis and neurotransmitter phe-
notypes, even though rSNA is not responsible for breathing
behaviors. FBMs play a role in lung maturation, but it is
unclear how FBMs correlate to rSNA, perhaps due to the
difficulty in studying rSNA and FBMs in the same animal
model.
The number of muscles that may contribute to ventila-
tion is large. Most of the muscles are close to the midline
of the body, and a disproportionate number of respiratory
muscles serve the pharynx and larynx, reflecting the vital
importance of upper airway patency in breathing and the
remarkable number of functions that involve the upper airway
(Table 1). The innervation, activation, and morphology of the
respiratory muscles reflect divergent developmental origins
of muscle-specific myogenic lineages. Cranial and somatic
myogenesis derive from unique genetic programs: muscles
innervated by cranial nerves are often activated before the
onset of inspiration and have different patterns of control
during wakefulness and sleep compared to somatic muscles
innervated by spinal motor neurons. Moreover, some muscle-
specific myopathies can be linked to lineage-specific genetic
programs (194). Functional studies of muscles are not, on
their own, enough to determine the genetic, developmental,
and migratory histories of founder cell populations nor to help
us understand how their molecular machinery influences the
etiology of developmental, muscular breathing disorders.
Beyond the diversity of actions and the large number
of respiratory muscles, the more impressive aspect of these
muscles is the complex ways in which they are coordinated
across a range of physical activities (27). Respiration can
be accomplished with a remarkably small number of mus-
cles when metabolic demand is low, as for example during
REM sleep when only a small group of respiratory muscles
is active. As metabolic demand rises, the number of muscles
and the intensity of activation of each muscle is increased. The
recruitment of muscles without a dominant respiratory func-
tion is not stereotypically identical for all possible increases in
metabolic or volitional demand; the activation patterns can be
quite sophisticated and task-specific so that different patterns
and intensities of activation of accessory muscles may accom-
pany exercise that is performed with the arms or with the legs,
or tasks such as weight lifting or a maximal inspiratory effort
that are performed at a standstill.
1071
The Muscles of Breathing
The capacity for speech and a bipedal posture have signif-
icantly affected respiratory muscle function in humans. First,
elongation of the pharynx and the descent of the larynx to
optimize the upper airway for speech have compromised the
respiratory function of the upper airway and made the pharynx
vulnerable to dynamic inspiratory compression (most com-
monly during sleep). Second, the upright posture has freed
the hands to become versatile tools to manipulate the exter-
nal world, and in so doing, the locomotor function of the
upper extremities has been reduced. Nevertheless, the com-
mon pattern of development from shared muscular primordia,
the common pattern of muscle innervation, and the sharing
of elements of spinal locomotor and respiratory pattern gen-
erators means that coordination and/or entrainment of the
respiratory rhythm to locomotor rhythms driving arm or leg
movements may still occur. On the other hand, muscles of the
shoulder girdle and upper thorax that were formerly required
for locomotion are more easily diverted to serve respiratory
functions when extreme respiratory efforts are required or
when these muscles must compensate for diminished func-
tion of the diaphragm and/or intercostal muscles following
injury or illness. Thus, respiratory muscles are activated in
complex, coordinated, and quite subtle ways. Such flexibil-
ity and precision are required to achieve an adequate rate and
depth of breathing first, but also various behaviors that require
sharing of the “respiratory muscles.”
The study of respiratory muscles remains a rich area of
investigation. Future studies need to tackle the ramifications
of emerging electrical activity in the CNS during the early
embryonic period as they pertain to the neural plasticity of
rSNA, and formation of the nascent breathing circuit. More-
over, the specific activation patterns of accessory muscles
during various respiratory behaviors deserve further elabora-
tion. How the nervous system controls multiple muscles that
are required for successful completion of a range of different
behaviors will continue to be a fruitful area of investigation.
Thus, understanding the origins, ontogeny, and functions of
respiratory muscles is sure to provide clinical benefit, whether
the patient is a preterm infant or an adult with neuromuscular
disease or injury.
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