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Clinical Neurophysiology of The Vestibular System (001-057) PDF
Clinical Neurophysiology of The Vestibular System (001-057) PDF
Clinical Neurophysiology of The Vestibular System (001-057) PDF
2001
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FOREWORD TO
THE FIRST EDITION
vii
PREFACE
The purpose of this book is to provide a framework for understanding the patho-
physiology of diseases involving the vestibular system. The book is divided into
four parts: I. Anatomy and physiology of the vestibular system; II. Evaluation of
the dizzy patient; III. Diagnosis and management of common neurotologic dis-
orders; and IV. Symptomatic treatment of vertigo. Part I reviews the anatomy and
physiology of the vestibular system with emphasis on clinically relevant material.
Part II outlines the important features in the patient’s history, examination, and
laboratory evaluation that determine the probable site of lesion. Part III covers
the differential diagnostic points that help the clinician decide on the cause
and treatment of the patient’s problem. Part IV describes the commonly used
antivertiginous and antiemetic drugs and the rationale for vestibular exercises.
This completely reorganized and expanded third edition covers the rapid
advances that have occurred in the basic and clinical vestibular sciences in the past
10 years. Recent breakthroughs in our understanding of peripheral transduction
and central processing mechanisms within the vestibular system are reviewed.
We discuss the differential diagnosis of dizziness of both vestibular and non-
vestibular etiology and describe several new bedside tests of vestibular function.
There is a new up-to-date chapter on the laboratory diagnosis of vestibular
dysfunction. In Part III, the chapter on benign paroxysmal positional vertigo
includes all the latest treatment maneuvers, and there are new chapters on
migraine and vertigo, immune-mediated vestibular disorders, and inherited
vestibular disorders. The newly added Part IV provides a strategy for deciding
on which drugs to use for symptomatic control of vertigo and for designing a
vestibular exercise program for patients with different types of vestibular lesions.
We believe that this book will be useful to all physicians who treat patients
complaining of dizziness. It should be particularly helpful for those in the field
of family practice, internal medicine, neurology, head and neck surgery, and neu-
rosurgery. Finally, we hope that it will encourage students (in both the clinical
and basic sciences) to choose neurotology as their field of study.
R. W. B.
V. H.
ix
ACKNOWLEDGMENTS
Our colleagues in Neurology and Head and Neck Surgery provided inspiration.
Kate Jacobson was instrumental in all aspects of the book preparation; she made
many of the figures and tables, she helped in the search for the latest references,
and she typed the manuscript. Finally, we are grateful for the continued support
of our work by the National Institutes of Health.
xi
CONTENTS
Part I Anatomy and Physiology of the Vestibular System
VESTIBULO-OCULAR REFLEXES 61
Experimental Methods • Organization of Vestibulo-ocular
Reflex Arcs • Characteristics of Eye Movements Induced by
Stimulation of Semicircular Canals • Characteristics of Eye
Movements Induced by Otolith Stimulation • Interaction of
Semicircular Canal– and Otolith-Induced Eye Movements
xiii
xiv Contents
VESTIBULOSPINAL REFLEXES 88
Comparison of Ocular and Spinal Vestibular Reflexes •
Vestibulospinal Pathways • Cerebellar–Vestibular Interaction •
Vestibular Influence in the Control of Posture and Equilibrium
6. LABORATORY EXAMINATION OF
THE VESTIBULAR SYSTEM 152
ELECTRONYSTAGMOGRAPHY 152
Methods of Recording Eye Movements • Interpreting the
Recording • Recording Pathologic Nystagmus • Bithermal Caloric
Test • Tests of Visual–Ocular Control
ROTATIONAL TESTING OF VESTIBULO-OCULAR
REFLEXES 172
Relationship between Stimulus and Response • Results in Normal
Subjects • Results in Patients
VISUAL–VESTIBULAR INTERACTION 187
Methodology • Results in Normal Subjects • Results in Patients
TESTS OF OTOLITH-OCULAR REFLEXES 191
Ocular Counterrolling • Eccentric Rotation • Off-Vertical
Rotation • Linear Acceleration
VESTIBULOSPINAL TESTING 193
Static-Force Platforms • Moving-Platform Posturography
VESTIBULAR-EVOKED POTENTIALS 194
PETROSITIS 222
Pathophysiology • Diagnosis • Management
MANAGEMENT 259
Medical Management • Surgery
GENETICS 269
PATHOPHYSIOLOGY 270
DIAGNOSIS 272
MANAGEMENT 272
DIAGNOSIS 298
Clinical Examination • Brain Imaging • Arteriography
xviii Contents
TREATMENT 302
Transient Ischemic Attacks • Infarction Syndromes
INTRALABYRINTHINE HEMORRHAGE 304
Diagnosis and Management
HEMORRHAGE INTO THE BRAIN STEM
AND CEREBELLUM 305
Diagnosis and Management
OTOTOXINS 340
Aminoglycosides • “Loop” Diuretics • Anti-inflammatory
Drugs • Platinum Compounds • Diagnosis • Management
NEUROTOXINS 344
Heavy Metals • Organic Solvents • Diagnosis • Management
INDEX 393
Part I
Anatomy and
Physiology of
the Vestibular
System
Chapter 1
VESTIBULAR FUNCTION:
AN OVERVIEW
The vestibular system interacts with other Newton’s second principle) is equal to the
sensory systems—particularly the visual product of their mass (m) and their accel-
and somatosensory systems—to perceive eration (a): F ma.* Since the mass of the
the relative motion between self and objects end-organ is constant, the force associated
in space and to maintain equilibrium. The with head acceleration generates a signal in
ensuing sensory and motor interactions the labyrinth that is proportional to the
contribute to orientation, a phenomenon head acceleration. The mathematical oper-
that is different from that of all of the ele- ation required to convert an acceleration
ments acting individually. signal to a measure of head displacement
The vestibular sensory organs contribute involves two integrations—one to obtain
to orientation by transducing the forces as- head velocity from acceleration and the
sociated with head acceleration and gravity other to obtain head displacement from ve-
into a biologic signal. The control centers locity. The first transformation is accom-
in the brain use this signal to develop a sub- plished in part by the end-organ, the sec-
jective awareness of head position in rela- ond by the central nervous system (CNS).
tion to the environment and to produce Inertial guidance systems that control the
motor reflexes for equilibrium, relating trajectory of space vehicles include the
these experiences to those of other sensory same basic components: a monitor of
systems during locomotion. The vestibular displacement based on sensors for linear
system, by means of its receptors for the
perception of linear and angular accelera-
*If mass is in kilograms and acceleration is in me-
tion, plays a central role in orientation. ters/sec2, then the unit of force is the newton (the force
During head movement, the force (F) ex- acting on a kilogram of mass to impart an accelera-
erted upon the vestibular end-organs (from tion of a meter/sec per second).
3
4 Anatomy and Physiology
and angular acceleration, and a central mately 2.7). The otolith is composed of cal-
processor that integrates this information, careous material embedded in a gelatinous
computing the coordinates of the space matrix and has a mean thickness of 50 mm
position. The central processor also main- (Fig. 1–1A). The position of the load on the
tains a memory of the trajectory and can receptor depends on the magnitude and di-
therefore make appropriate adjustments in rection of the force acing upon it (Fig.
course when necessary.1 Here the similar- 1–1B, C).4,5 Even when the head is at rest,
ities of vestibular organs to space vehicle the calcareous material, because of its mass,
guidance systems end, for they do not ex- exerts a force (Fg) upon the receptor equal
plain the complex operational capabilities to the product of its mass and the acceler-
of the brain in support of the sensory ation due to the gravitational pull of the
function of orientation. The performance earth (g), which at sea level is 9.80 m/sec2.
of space vehicles is based upon prepro- The distribution of Fg acting upon the un-
grammed strategies while the brain can re- derlying sensory cells changes with different
solve even the most unexpected conflicts. degrees of head tilt and can be represented
For example, the direction of the vestibulo- by two vectors (Fig. 1–1B): one vector (Ft)
ocular reflex can be reversed (i.e., the eyes tangential and the other (Fn) normal to the
will move in the same direction as that of surface of the receptor. The value of the tan-
the head instead of in the opposite direc- gential vector is proportional to the sine of
tion) if one wears glasses with reversing the angle made by Fg with Fn (i.e., the
prisms for several days or even hours.2 Pa- angle of tilt). As will be shown later, it is
tients with vestibular system disorders can this tangential force (Ft) and the resulting
adapt rapidly to perturbed disequilibrium. otolith displacement that constitute the ef-
The neuroanatomic and physiologic sub- fective stimulus to the sensory cells.
strates for this capability are becoming bet- During linear head acceleration tangen-
ter understood, opening new avenues of re- tial to the surface of the receptor (Fig.
search in the study of vestibular function in 1–1C), the instantaneous force (Fg) acting
health and in disease.3 upon the macules is also the result of two
vector forces: one (Ft) in the direction op-
posite to that of head acceleration and the
BIOPHYSICAL BASIS OF other (Fg) due to gravitational pull. Again,
VESTIBULAR RECEPTOR the effective force producing otolith dis-
SPECIALIZATION placement is the tangential force (Ft). In
both cases, the sensory cells of the macules
The vestibular system monitors the forces transmit information on the displacement of
associated with angular and linear accel- the otolith membrane to the CNS; here, re-
erations of the head by means of five or- flexes are initiated to contract muscles that
gans located within the labyrinthine cavi- dynamically oppose the force acting upon
ties of the temporal bones on each side of the head and thus maintain equilibrium.
the skull. The saccular and utricular mac- A classic example of an otolithic reflex is
ules sense linear acceleration, and the the change in eye position of fish, amphib-
cristae of the three semicircular canals ians, and rodents when their heads and
sense angular acceleration of the head. The bodies are tilted from the horizontal and
capacity of the macules and cristae to func- held in that position. In such a condition,
tion as sensors of these kinds of accelera- the eyes align themselves in the orbits to
tion rests on their anatomic configurations. maintain their normal relation parallel to
the horizon.6–8 To achieve this goal, the ex-
traocular muscles of the eyes acquire a new
Macules level of contraction, or tone, that remains
unchanged as long as the head is held in
Each macule consists of a sensory mem- the new position. Thus the macules send
brane containing the receptor cells with a information about the direction of the grav-
surface area 1 mm2 that supports a “heavy itational vector in relation to the surface
load,” the otolith (specific gravity, approxi- of the sensory epithelium. Because of the
Vestibular Function: An Overview 5
Figure 1–1. A graphic illustration of the main anatomic features of the macules (A) and the distribution of forces
associated with static head tilt (B) and linear acceleration tangential to the surface (C) (for orientation of sensory
cells in each macule, see Fig. 2–7). Fg gravitational force, Fn, normal force; Ft, tangential force.
permanence of the muscle tone, such re- they sense the displacement of the fluid
flexes have been classically known as the during head rotation. The sensory ep-
static labyrinthine reflexes and, accord- ithelium of the cristae is covered by a bul-
ingly, the macules, as the static labyrinthine bous, gelatinous flexible mass called the
organs.7,8 However, as we will see later, the cupula, resting upon the sensory cells.
macules are also sensitive to transient lin- Since the cupula-specific gravity is the
ear accelerations and participate in most same as that of the surrounding fluid, un-
dynamic vestibular reflexes. like the otolith of the macules, the cupula
does not exert a resting force on the un-
derlying sensory epithelium. The crista is
Cristae insensitive to the static gravitational vec-
tor or position of the head in space. How-
Natural head movements consist of a com- ever, the cupula and fluid can be displaced
bination of linear and rotational vectors, along the lumen of the canal when an ap-
the latter acting upon a different set propriate force is introduced in the canal,
of sensors located in the semicircular and because of its narrow diameter, the
canals.9,10 The canals are small rings ap- fluid can move only longitudinally. This oc-
proximately 0.65 cm in transverse diam- curs during angular acceleration of the
eter with an inner cross-sectional diame- head while rotating in the plane of the
ter of 0.4 mm (Fig. 1–2). They are filled semicircular canal. The force associated
with fluid that has a density and a viscos- with the rotation displaces the fluid relative
ity slightly greater than those of water.11 to the wall of the canal. The motion of the
The receptor organs, the cristae, are cupula acts as a stimulus to the underlying
mounted in the wall of the rings, where sensory epithelium. That is, the semicircular
6 Anatomy and Physiology
canal is a sensor of the angular motion of slow components joined end to end, the re-
the head in the plane of the canal. sulting sinusoidal eye movement would
The semicircular canal reflexes have continue to be approximately equal in mag-
been called phasic, or kinetic, because they nitude and opposite in direction to the
are thought to be primarily responsible for sinusoidal head movements as seen in
muscle contractions associated with the Figure 1–3a, b. Thus the quick component
maintenance of equilibrium during mo- of nystagmus is a strategy developed by the
tion. An example of a semicircular canal re- brain to increase the functional capabilities
flex is the compensatory eye movement as- of the reflex.
sociated with head rotation. This reflex is
present throughout the animal kingdom
and is exemplified in the rabbit as shown CLASSIFICATION OF
in Figure 1–3. Head rotation to one side VESTIBULAR REFLEXES
results in eye movement in the opposite di-
rection in order to maintain a stable gaze The rationale for classifying the cristae of
for clear vision.12 If the head rotation ex- the semicircular canals as kinetic receptors
ceeds that which can be compensated for and the macules of the utricle and saccule
by motion of the eye in the orbit within ap- as static receptors was based on a narrow
proximately 20 (e.g., in Fig. 1–3d), the view of their overall function. Both sets of
reflex takes the form of nystagmus. This is receptor organs produce motor reflexes
a back-and-forth eye movement in which a that cannot be differentiated on the basis
slow deviation, lasting between 0.5 and of the resulting movement. It is more ap-
2 sec, is interrupted by a flick in the oppo- propriate, therefore, to differentiate the re-
site direction lasting 0.1 to 0.2 sec. If the flexes by categories based on their func-
fast components were removed from the tional role rather than on the receptor from
bottom tracings in Figure 1–3c, d and the which they originate.
Vestibular Function: An Overview 7
Figure 1–3. Compensatory eye movements in the rabbit that are produced by sinusoidal angular acceleration of
the head (0.2 Hz) at four different peak angular displacements ().
At least three major functional roles for skeletal-muscle tone can be demonstrated
vestibular reflexes can be identified. The by the change in posture that follows uni-
first is to maintain posture, namely, the up- lateral labyrinthectomy in normal ani-
right position in relation to the earth ver- mals.7,15 Tone is increased in the extensor
tical. Vestibular reflexes of this kind induce muscles of the contralateral extremities and
muscle contractions that produce negative decreased in the ipsilateral extensor mus-
geotropic movement or forces that com- cles. An even more striking demonstration
pensate for steady changes in the direction of the vestibular role in maintenance of
of the force of gravity. If the pull of grav- muscle tone is the removal of decerebrate
ity on the body were unopposed by forces rigidity after sectioning of both vestibular
developed in the muscles, the body would nerves or destruction of the vestibular nu-
collapse. Reflexes in this category in hu- clei.16,17 The extensor rigidity that results
mans are dependent on the function of the from transection of the nervous system
macules but not on that of the semicircular at the caudal end of the mesencephalon
canals. The second role is to produce “ki- is markedly decreased when the tonic
netic,” or transitory, contractions of mus- labyrinthine input is removed.
cles for maintenance of equilibrium and The characteristically high spontaneous
ocular stability during movement. This cat- firing rate of action potentials from the pri-
egory includes reflexes arising from both mary vestibular afferents provides a con-
the semicircular canals during angular ac- stant level of neural activity to the neurons
celeration and the otolithic organs during in the vestibular nuclei.18 The peripheral
linear acceleration. Most natural head vestibular influence also affects the re-
movements contain both types of accelera- sponse of the vestibular nuclei neurons to
tion, and the vestibular reflexes act in com- the converging inputs from other systems
bination to maintain equilibrium. A third (vision, proprioception, segmental motor
role of vestibular reflex activity is to help reflexes) and from neurons in the opposite
maintain muscular tone, a role in which side of the brain as well.19 An integration,
both the macules7,8,13 and cristae partici- in the mathematical as well as the physio-
pate.14 The labyrinthine contribution to logic sense, takes place in the brain stem by
8 Anatomy and Physiology
means of commissural and reverberating tors of water pressure waves in their vicin-
circuits20,21 (see Chapter 3). ity (Fig. 1–4B). Among important signals
are vibrations produced by minuscule prey
animals. The neuron reaction leads to a
PHYLOGENY OF THE “motor” response involving a sensory cell,
VESTIBULAR SYSTEM a surrogate vestibular nucleus, and an ef-
fector neuron. The reflex response consists
The role of the labyrinth in maintaining of the secretion of a paralyzing substance
orientation has remained the same from by the enmatocyst, the “stinging organelle”
the earliest organisms in the animal king- of the anemones.
dom.22–28 However, as with other sensory From these simple mechanotransduction
organs, both functional and morphologic receptors to the labyrinth of higher ani-
changes have evolved. Only the most prim- mals, a continuous increment in anatomic
itive forms of life, such as Monera (bacteria complexity occurs that accompanies the phy-
and blue-green algae) and Protista, which logenetic evolution of the taxa (Fig. 1–5).
include many unicellular organisms (fla- Next developmentally are the mechanore-
gella), have been able to adapt to the envi- ceptors of mollusks (e.g., octopus, sepia),
ronment without specialized receptors for in which both types of receptors, the static
the detection of gravitational force. In these otolith and the kinetic cristae receptors,
animals, as well as in plants, geotropic mo- appear in the form of macules and
tion is probably due to the difference in semicircular canals. These new receptors,
density of undifferentiated parts that “de- incorporated in an invaginated com-
tect” the pull of gravity. For example, when mon cavity, accompany the appearance
the stem of the plant Bryophyllum calycinium of motor responses to motion, includ-
is placed in a horizontal position, certain ing nystagmus.27,28 In primitive fish
chemical substances gather in greater con- (cyclostomes), the statocyst cavity, previ-
centration on the lower side of the stem, ously open to the outside, is closed and
causing it to grow faster than the upper filled by an endogenous secretion (en-
side. Thus the stem is forced to grow in a dolymph).
vertical direction known as gravitropism.29,30 Two surviving cyclostomes, the hagfish
The most primitive gravity-detection or- and the lamprey, demonstrate an impor-
gan, the statocyst, appeared more than 600 tant step in the phylogenetic development
million years ago in the late Precambrian of the vestibular labyrinth. In the hagfish,
era.22,23 It is present in some bygastrulated a simple circular tube is interrupted ante-
animals with the most developed Coelen- riorly and posteriorly by bulbous enlarge-
terata, such as jellyfish, allowing the animal ments, the ampullae, each containing a
to orient itself in relation to the horizon by primitive crista. Between the ampullae, in
sensing the direction of the gravitational an intercommunicating channel, lies the
force of the earth. The statocyst is a fluid- macule communis, the forerunner of the
filled invagination or sac containing a cal- utricular and saccular macules. The
careous particle, the statolith, or multiple labyrinth of the lamprey is more complex,
particles, the statoconia, of a density greater consisting of an anterior and posterior
than that of the fluid (Fig. 1–4A). Attracted canal communicating with a bilobulated
by gravity, the particles rest their weight dif- sac containing separate utricular and sac-
ferentially over special sensory cells in the cular macules. The predecessor of the au-
wall of the cyst, providing information for ditory organs appears after the develop-
the animal to regulate its static position in ment of a membranous labyrinth that is
space. divided into two cavities. In the inferior
A primitive receptor organ for generat- of the two cavities (the saccule), two new
ing a vestigial kinetic reflex has recently receptor areas develop—the lagenar mac-
been found on tentacles of primitive ma- ule and the basilar papilla. In crocodiles,
rine invertebrates, sea anemones.25,26 A however, these receptors are contained in a
sensory neuron is coupled to two neigh- cavity separate from the saccule, while in
boring hair cells that act as mechanorecep- birds the basilar papilla is a long, uncoiled
Vestibular Function: An Overview 9
organ, the predecessor of the coiled cochlea organ of modern fish to represent the
(Fig. 1–5c).28 “highest perfection” of the vertebrate organ
With the advent of modern fish (about of equilibrium. The utricle and semicircu-
100 million years ago) the vestibular lar canals are relatively larger than those in
labyrinth reached its peak of development, other classes of vertebrates. Since fish do
and relatively little change has taken place not have the highly developed afferent sys-
since that time. The basic structure of the tems of proprioception, touch, and vision
three semicircular canals, the utricle, and that higher vertebrates possess, they are ap-
the saccule is similar in all higher verte- parently more dependent on the labyrinth
brates. Gray considered the vestibular end- to provide orienting information.
10 Anatomy and Physiology
Figure 1–5. Phylogeny of the labyrinth. (a) myxine; (b) petromyzon; (c) bird; (d) mammal. C. ant., anterior canal;
C. lat., lateral or horizontal canal; C. post., posterior canal; M. comm., common macule; M. lag., lagenar mac-
ule; M. negl., neglector macule; M. sacc., saccular macule; M. utr., utricular macule; Pap. bas., basilar papilla.
(From Wersall DJ, Bagger Sjoback D. Morphology of the vestibular sensor organs. In: Kornhuber, HH (ed).
Handbook of Sensory Physiology, Vol Vl, Part 2. Springer Verlag, New York, 1974, with permission.)
nerve from the utricle and horizontal and tion) and pathways for interaction of these
anterior semicircular canals and some of systems with the vestibular system. The
the nerve fibers from the saccule form the vestibular nuclei are one of the first
superior division of the vestibular nerve; supraspinal cell groups that differentiate
most nerve fibers from the saccule and the themselves from the reticular forma-
nerve from the posterior semicircular canal tion.36,37 Lampreys have two discernible
contribute to the inferior branch (Fig. 1–6). vestibular nuclear groups, the dorsal and
The afferent fibers from the auditory or- ventral, composed of granular and spindle-
gan form a separate nerve anterior and in- shaped cells. Modern fish (teleosts) have
ferior to the vestibular nerve to innervate four discernible vestibular nuclei, although
the organ of Corti, the auditory receptor the nuclei contain relatively few cells. This
organ. Together these two nerves constitute basic organization of four vestibular nu-
the eighth cranial nerve and, within them, clear groups is maintained throughout the
a system of efferent fibers from the CNS higher vertebrates, although the relative
gates or modulates the activity of the pe- size of each nuclear group varies from
ripheral organs.32–34 Phylogenetically, this species to species.
neural feedback system is already present In invertebrates and early vertebrates,
in gastropods, in which action potentials di- secondary connections of the vestibular nu-
rected from the brain to the receptors have clei are primarily vestibulospinal, in keep-
been recorded.35 ing with their major role in maintaining
In comparison with the vestibular sen- body orientation.38 Vestibulocerebellar con-
sory organs, central vestibular connections nections become progressively more promi-
become progressively more complex in nent in higher vertebrates. The develop-
higher vertebrates (see Chapter 3). This ment of these “modern” vestibular pathways
complexity accompanies the development accompanies the development of increas-
of other afferent systems for the mainte- ingly complex somatic and ocular motor
nance of equilibrium (vision, propriocep- skills. In primates, vestibulocerebellar and
Figure 1–7. Schematic drawing of the two types of hair cells. Inset illustrates relationship between the direction
of force and maximum hair cell activation.
hair cells of amphibians and mammals leading to depolarization of the hair cell
have expanded our knowledge of the membrane and release of neurotransmit-
mechanoelectric transduction process.49,50 ters. There is a diversity of ion channels
When hair cells are stimulated, there is a expressed in the hair cells.51, 52 For exam-
change in the electric current beginning at ple, type I hair cells express a K channel
the tips and the lumen of the stereocilia to that results in an unusually low input re-
the inside of the cell. This “transduction” sistance compared to that expressed by
current causes a series of additional type II hair cells.53
changes in the permeability of different ion Measurement, with intracellular elec-
channels in the basolateral membrane trodes, of the hair cell responses to cilia
14 Anatomy and Physiology
Figure 1–8. Mechanism of hair cell activation. Sinusoidal displacement of the stereocilia produces a sinusoidal
modulation or the vestibular nerve firing rate. See text for details.
deflection shows that the curve relating the activating chemical transmitters to modu-
receptors’ potential to the stimulus has late the firing of action potentials by the af-
greater sensitivity and linearity for small ferent neurons (Fig. 1–8).
signals.54,55 Larger stimuli exhibit satura- Hair cells are not passive elements; they
tion or nonlinearity that is greater for hy- actively participate in the mechanotrans-
perpolarizing than for depolarizing stimuli, duction process.41,56 In particular, outer
leading to smaller responses, hence lower cochlear hair cells, which contain several
gains for deflection away from the kinocil- contractile proteins,57 vary their length
ium (Fig. 1–9). The voltage drop produced under direct electrical stimulation.58,59
in the vicinity of the hair cells by the chang- Recently, through a combination of so-
ing current is known as the microphonic po- phisticated electrophysiological and molec-
tential, the so-called generator potential of ular techniques, it was shown that elec-
these receptor organs.42,46 It is maximal at tromotility of the outer hair cells is
the tips of the hairs.48,55 In contrast to dependent on a new protein, prestin, iso-
nerve action potentials, the generator po- lated with comparative cDNA analysis of
tentials have no refractory period (follow- the inner and outer hair cells.60 Recombi-
ing the frequency of the stimulation above nant prestin introduced into cultured kid-
several thousand hertz), are highly resist- ney cells provides them with contractile
ant to anoxia, and may remain partially properties normally not present. Presum-
active after the animal’s death. The electric ably, during acoustic stimulation, prestin
current associated with the generator po- experiences an electric charge realignment
tentials acts upon the synaptic contacts that results in morphological changes in the
between hair cells and nerve terminals by shape of the outer hair cells, elongating
Vestibular Function: An Overview 15
Figure 1–9. Intracellular voltage changes (mV) associated with displacement of cilia of a hair cell from the frog
saccule. Cilia bending toward the tallest stereocilia produce a positive depolarizing change whereas motion in
the opposite direction results in a negative hyperpolarizing change. Note that the curve relating the receptor
potential to the degree of deflection (m) has the greatest sensitivity and linearity for small deflections and
exhibits a saturation nonlinearity for large displacements that is greater for hyperpolarizing than depolarizing
stimuli. (From Hudspeth AJ, Corey DP. Sensitivity, polarity, and conductive change in response of vertebrate
hair cells to controlled mechanical stimuli. Proc Natl Acad Sci USA 1977;74:2407–2411 with permission.)
during hyperpolarization and contracting One of the most significant findings con-
during depolarization. These conforma- cerning hair cell function was the discovery
tional changes would influence the dis- by Hoagland in 1932 that the afferent nerves
placement of the basilar membrane in a from lateral-line organs of fish generated
positive feedback configuration facilitating continuous spontaneous activity.64 This ob-
the physiological stimulation of inner hair servation has subsequently been confirmed
cells, in essence acting as the amplifier of in all other hair cell systems and represents
the acoustic energy entering the ear.61 In a fundamental discovery in sensory physiol-
vestibular hair cells, the stereocilia contain ogy. While the mechanism responsible for
actin molecules and can carry out flagella- the spontaneous firing of action potentials in
type movement.53,62,63 The cilia length the afferent nerves is not completely known,
varies among hair cells and location, but it depolarization and hyperpolarization of the
is logical to expect that anatomic differ- hair cells’ membrane potential result in a
ences in stereocilia will result in differences modulation of this spontaneous activity.
in the process of transducing head-motion Bending of the hairs toward the kinocilium
information into neural signals. Although results in an increase of the spontaneous fir-
not proven, it is possible that hair cells at ing rate, and bending of the hairs away from
the periphery of the vestibular organs ac- the kinocilium results in a decrease of the fir-
tively pull the cupula or otolithic mem- ing rate.65 The spontaneous firing rate varies
brane to influence the response of the more in different animal species and in different
centrally placed hair cells, analogous to the sensory receptors. It is thought to be great-
effect of cochlear outer hair cells on inner est in the afferent neurons of the semicircu-
hair cell walls. lar canals of mammals (up to 90 spikes/sec)
16 Anatomy and Physiology
and lowest in some of the acoustic nerve In the cochlea, the hair cells are mounted
fibers innervating mammalian cochlear hair on the flexible basilar membrane in the or-
cells (1 to 2 spikes/sec).18,66 Given the non- gan of Corti. Covering the organ of Corti
linear behavior of the hair cell transduction and resting over the hair cells is the tector-
mechanism, it is not surprising that the mod- ial membrane, a relatively rigid structure at-
ulation of the spontaneous neuronal firing tached to the wall of the cochlea. A small,
rate is likewise nonlinear. Responses to exci- acoustically induced pressure difference
tatory stimuli are less than those to inhibitory across the basilar membrane causes the or-
stimuli. This characteristic is of great physi- gan of Corti and hair cells to vibrate at the
ological and clinical significance, as will be frequency of sound. The motion of the basi-
shown later. lar membrane has a different effect on the
outer hair cells than on the inner. Outer hair
cells have their cilia embedded in the tecto-
Basis for Stimulus Specificity rial membrane and are directly stimulated
of Inner Ear Receptor Organs as the cilia are displaced in relation to the
relatively fixed tectorial membrane, which
As suggested earlier, the density of the acts as a hinge.42 In contrast, the inner hair
otolithic membrane overlying the hair cells cell cilia are not embedded in the tectorial
of the macule is greater than that of the membrane but are instead surrounded by
surrounding endolymph. The hair cell endolymph. Their stimulation is produced
cilia are embedded in the otolithic mem- by the dragging viscous force of the fluid on
brane and, when displaced, produce a the cilia. Intracellular recordings in mam-
shearing force (Ft) on the underlying hair malian cochlear hair cells show a difference
cells that is proportional to the sine of the of phase between the receptor potentials of
angle between the line of resulting gravi- the inner and outer hair cells as predicted
tational vector and a line perpendicular to by the difference in the coupling of the cilia
the plane of the macule (see Fig. 1–1). Each to the tectorial membrane.49 The outer
macule is bisected by a distinctive curved hair cells respond to position and the in-
zone, the striola. Hair cells are oriented in ner hair cells respond to the velocity of the
opposite directions on each side of the stri- basilar membrane motion.
ola so that displacement of the otolithic In all cases, the effective stimulus to the
membrane has an opposite effect on the sensory cells is the relative displacement of
set of hair cells on each side of the striola the cilia produced by application of me-
(see Fig. 2–9). chanical force to their surroundings. Since
The hair cell cilia in the cristae of the the mechanical properties of the “support-
semicircular canals are embedded in the ing and coupling” structures are different,
cupula, a jelly-like substance of the same the frequency ranges at which the cilia can
specific gravity as that of the surrounding be moved by the applied force are differ-
fluids. The cupula, therefore, does not ex- ent. Because of the great flexibility of the
ert a force on the underlying crista and is basilar membrane, the range of sound fre-
not subject to displacement by changes in quencies to which the hair cells in the
the line of gravitational force. The forces cochlea are sensitive varies from 20 to
associated with angular head acceleration, 20,000 Hz. In the macules, the otoconia are
however, do result in a displacement of maximally displaced during accelerations
the cupula that stimulates the hair cells of such as those associated with steady head
the crista in the same way that displace- displacement. Owing to the characteristics
ment of the otoliths stimulates the macu- of the restraining viscoelastic forces hold-
lar hair cells. However, in the cristae, all ing the otoliths to the macule, their motion
the hair cells are oriented in the same di- rapidly diminishes if the linear accelera-
rection in the crista surface. All hair cells tion changes at a frequency 0.5 Hz.5 The
are either excited or inhibited by motion semicircular canals also respond maxi-
of the fluid in the canal, but the orienta- mally to constant angular acceleration, but
tion is different in different semicircular they can respond to changes in angular ac-
canals. celeration as high as 40 to 50 Hz.10 This
Vestibular Function: An Overview 17
frequency limitation is due to the inertial opposite directional sensitivity of the hair
and viscous forces restraining the displace- cells in the left crista. Neurons in the left
ment of fluid and cupula in the narrow vestibular nucleus are affected in a similar
semicircular canals. fashion; that is, increased firing of excita-
tory and inhibitory neurons in the right
vestibular nucleus and decreased firing of
ORGANIZATION OF CENTRAL excitatory and inhibitory neurons in the left
VESTIBULAR PATHWAYS vestibular nucleus occur. By this process,
each nucleus reinforces the information ar-
Vestibular Reflexes riving from the periphery. A four-way bal-
ance mechanism is at work in which the ac-
The basic elements of a simple vestibular tivity of the agonist muscles benefits from
reflex arc are a hair cell, an afferent bipo- the increased activity of the ipsilateral hor-
lar neuron, an interneuron, and an effec- izontal canal crista and the decreased inhi-
tor neuron.67 This simple three-neuron bition of the contralateral horizontal crista.
reflex arc is already developed in the phy- The activity of the antagonistic muscles is
lum Mollusca, among which the class reciprocally affected so that the control of
Cephalopoda has contributed to many muscle tone is a four-way push–pull system.
classic anatomic and physiologic studies of The loss of one ear is not an irreparable
gravitational reflexes.22 Vestibular reflexes condition because by rearrangement of the
have developed further in vertebrates and weight of the signals in the CNS, a balance
mammals with the addition of multiple can be reestablished. This process is known
neuronal pathways.67 as central vestibular compensation.
The terminal fibers of the afferent neu- This general plan of organization applies
ron make synaptic contact with the hair cell to all labyrinthine-mediated reflexes. We
and transmit nerve signals to neuronal sen- have found this simplified system to be ex-
sory pools on the same side of the CNS (the tremely useful in the process of evaluating
vestibular nuclei) that contain both excita- patients and elucidating the pathophysio-
tory and inhibitory neurons. Besides re- logic changes associated with vestibular dis-
ceiving signals from excitatory first-order orders.
neurons from the ipsilateral ear, the exci-
tatory neurons also receive signals from the
inhibitory neurons of the contralateral side Interaction with Other Systems
by way of crossed neural pathways. The
output of the excitatory vestibular nuclei The maintenance of body equilibrium and
interneurons is transmitted to the effector posture in everyday life is a complex func-
motor pools, which consequently reflect the tion involving multiple receptor organs and
activity of both ears. The effector neuron, neural centers in addition to the labyrinths.
in turn, controls the activity in an appro- Visual and proprioceptive reflexes in par-
priate muscle to coordinate orienting be- ticular must be integrated with vestibular
havior. reflexes to ensure postural stability. The
The organization of the semicircular prominent role of sensory interaction in
canal–ocular reflexes is an excellent exam- orientation can already be appreciated in
ple of a three-neuron vestibular reflex. the behavior of gastropods. The inverte-
Clockwise angular acceleration in the plane brate Hermissenda has only rudimentary
of the horizontal canals results in an in- vestibular and visual receptors, yet the two
creased firing of the afferent nerve from systems fully interact to control behavior.68
the ampulla of the right horizontal semi- Afferent signals from photoreceptors in the
circular canal (Fig. 1–10). This afferent eye and from hair cells in the statocyst con-
signal is carried to both excitatory and in- verge on interneurons in the cerebroplural
hibitory neurons of the ipsilateral vestibu- ganglia, which control a putative motor
lar nucleus. The afferent nerves from the neuron in each pedal ganglion. Excitation
left horizontal semicircular canal crista de- of the motor neuron produces turning of
crease their neural activity because of the the animal’s foot in the ipsilateral direction,
18 Anatomy and Physiology
consistent with the animal’s turning behav- head rotation that would produce com-
ior toward light. In humans, during most pensatory eye movement in the dark does
natural head movements, gaze stabilization not do so in the light if the subject fixates
is achieved by a combination of vestibular, on a target moving in phase with the head
neck proprioceptive, and visual inputs; the (Fig. 1–11). In this simple example, failure
interaction can be synergistic or antagonis- to override the vestibular signal leads to
tic. For example, when the vestibularly in- disorientation.
duced eye movements lie in a direction The diagram in Figure 1–12 illustrates
opposite to that required to maintain the how different sensory systems—vestibular,
desired gaze position, the visual reflexes visual, proprioceptive, and auditory—
override the vestibular reflex. The kind of provide information to a first line of
Vestibular Function: An Overview 19
Figure 1–11. Eye movement induced in a normal human subject by sinusoidal angular acceleration (0.05 Hz,
maximum velocity 60/sec) in the dark and in the light with a target moving in phase with the subject.
Figure 1–12. Block diagram illustrating the organization of sensorimotor integration within the brain.
20 Anatomy and Physiology
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Chapter 2
THE PERIPHERAL
VESTIBULAR SYSTEM
23
Figure 2–1. Medial view of the temporal bone. (From Anson BJ, Donaldson JA. Surgical Anatomy of the
Temporal Bone and Ear. WB Saunders, Philadelphia, 1973, with permission.)
Figure 2–2. Cross section of the ear. (From Anson BJ, Donaldson JA. Surgical Anatomy of the Temporal Bone
and Ear. WB Saunders, Philadelphia, 1973, with permission.)
24
The Peripheral Vestibular System 25
The manubrium is attached, like the radius the cone-shaped tympanic membrane.
of a circle, to the inner side of the tympanic The medial, or labyrinthine, wall is an ir-
membrane in a superoanterior direction. regular surface because of the structures
Superiorly, the head of the malleus is bound bulging from the inner ear: the promon-
to the incus, forming the incudomalleal ar- tory of the basal turn of the cochlea and
ticulation, a type of diarthric joint. The so- the prominences of the facial canal and
called long process of the incus (7 mm), di- horizontal semicircular canal. Beneath the
rected down and anteriorly, is connected to cochlear prominence is the membrane of
the stapes, the smallest of the three middle the cochlea or round window, which seals
ear ossicles. The footplate of the stapes ar- the scala tympani of the cochlea and its
ticulates with the walls of the vestibule at the fluid from the middle ear. It provides an
oval window to which it is attached by a ring outlet for equilibrium of pressure in the
of ligaments. The dimensions of the window inner ear whenever sound displaces the
are 1.2 by 3 mm, with a total area that is stapes. Without this compliance, sound en-
one-seventeenth that of the tympanic mem- ergy could not displace the basilar mem-
brane. Sound-induced displacements of the brane of the cochlea because the en-
tympanic membrane and its attached dolymph fluid is incompressible. The
manubrium are transmitted through the vestibular, or oval, window is located just
medial arm of the assembly of middle ear above the cochlear prominence, where it
bones, acting as a lever to the inner ear; in is closed by the base of the stapes and the
this fashion the middle ear functions as a annular ligament.
mechanical transformer. Additional ampli- The anterior wall of the tympanic cavity is
fication is produced as the force applied marked by three important structures: the
over the surface of the tympanic membrane eustachian tube orifice, the wall of the
is funneled into the smaller area of the oval carotid canal, and the opening of the chan-
window. The middle ear compensates for nel for insertion of the tensor tympani mus-
the loss of energy—approximately a 99.9% cle. The eustachian tube connects the
loss—that would occur if sound were trans- middle ear cavity with the nasopharynx,
mitted directly from air to the fluids of the providing ventilation of the tympanic cavity
inner ear.6 spaces. The tubal orifice at the nasopharynx
The ossicles are suspended by several is normally closed, but during deglutition it
ligaments and are dynamically controlled opens owing to the contraction of palate
by the action of two muscles. The tensor muscles that are attached to the cartilage
tympani, innervated by a branch of the and elastic ligaments in the opening. The
trigeminal nerve, is connected by a tendon most important of the muscles, the tensor
to the upper part of the manubrium. veli palatini, is innervated by the trigeminal
Coursing in a lateral direction from the an- nerve. In the upper part of the posterior wall
terior part of the medial wall of the tym- of the tympanic cavity is a large opening con-
panic cavity, this muscle draws the tiguous with the epitympanic recess, the adi-
manubrium medially, tensing the tympanic tus ad antrum. Through this opening there
membrane. The stapedius muscle, inner- is the communication with the mastoid
vated by the facial nerve, is attached to the antrum. The antrum is lined with mucus
posterior wall of the tympanic cavity and membrane continuous with that of both the
is directed anteriorly to anchor in the up- tympanic and epitympanic cavities. The
per part of the stapes. Its contraction hin- antrum is a relatively large, irregular, bean-
ders the transmission of sound to the in- shaped cavity about l cm long. Many mas-
ner ear (Fig. 2–3). toid air cells open into this cavity that is lo-
cated behind and below the antrum within
BOUNDARIES the mastoid process of the temporal bone.
In addition to the antrum, the posterior wall
For descriptive purposes, the tympanic of the tympanic cavity contains an aperture
cavity can be thought of as being bounded through which the tendon of the stapedius
by six walls facing one another in pairs. muscle passes, another aperture through
The lateral wall is made up in large part of which the chorda tympani nerve enters the
The Peripheral Vestibular System 27
tympanic cavity, and a fossa where the pos- company in an anterosuperior position
terior ligament of the incus is attached. with the vestibular and cochlear divisions
The roof of the tympanic cavity is formed of the eighth nerve, while in its remaining
by the tegmen tympani, a thin plate of bone segments the facial nerve lies separately
separating the epitympanic recess of the within a bony canal—the facial or fallopian
tympanic cavity from the middle cranial canal. The labyrinthine segment runs at
fossa. The floor is composed of the jugular nearly a right angle to the petrous pyra-
bulb, upon which are located irregular mid superior to the cochlea and vestibule
pneumatized cells. to reach the geniculate ganglion. At the
geniculate ganglion, the nerve takes a
FACIAL NERVE sharp turn posteriorly, marking the begin-
ning of the tympanic segment. The hori-
The facial nerve arises at the inferior bor- zontal tympanic segment courses in a pos-
der of the pons and proceeds to the inter- terior direction along the medial wall of
nal auditory canal on the superior surface the tympanic cavity superior to the oval
of the cochlear nerve. Within the tempo- window and inferior to the horizontal
ral bone, four portions of the facial nerve semicircular canal. At the sinus tympani,
can be classified: (1) the canal (meatal) seg- the nerve bends inferiorly, marking the be-
ment (7 to 8 mm), (2) the labyrinthine seg- ginning of the vertical, or mastoid, segment
ment (3 to 4 mm), (3) the tympanic (hori- that continues toward the stylomastoid
zontal) segment (12 to 13 mm), and (4) the foramen. At this level, the facial nerve con-
mastoid (vertical) segment (15 to 20 mm) sists exclusively of motor fibers that inner-
(Fig. 2–4). The canal segment runs in close vate the muscles of the facial expression
after coursing through connective tissue lomastoid foramen causes only ipsilateral
septa in the parotid gland. Three major facial muscle weakness or paralysis.
groups of fibers have been recognized that
are directed to (1) the auricular and oc-
cipital muscles, (2) the orbicularis and mus- Inner Ear
cles of mimetic facial expression, and (3)
the buccinator and buccolabial muscles. BONY LABYRINTH
Three major branches of the facial nerve
lie within the temporal bone: (1) the Within the petrous portion of the tempo-
greater superficial petrosal nerve, arising ral bone, a series of hollow channels, the
from the geniculate ganglion; (2) the nerve bony labyrinth, contain the auditory and
to the stapedius muscle, arising from the vestibular sensory organs (see Fig. 2–2).
initial part of the mastoid segment; and The bony labyrinth consists of an anterior
cochlear part and a posterior vestibular
(3) the chorda tympani, leaving the facial
part.1 The vestibule is a central chamber
nerve approximately 5 mm above the sty-
(about 4 mm in diameter) marked by the
lomastoid foramen. The greater superficial
recesses of the utriculus and sacculus. The
petrosal nerve is composed of (1) parasym-
superior and posterolateral walls contain
pathetic efferent fibers originating in the
openings for the three semicircular canals,
superior salivatory nucleus for innervation
and anteriorly the vestibule is continuous
of the lacrimal glands and seromucinous
with the scala vestibuli of the snail-shaped
glands of the nasal cavity and (2) afferent
cochlea.
cutaneous sensory fibers from parts of the
Medial to the bony labyrinth is the inter-
external canal, tympanic membrane, and
nal auditory canal, a cul-de-sac housing the
middle ear, destined for the nucleus of the
seventh and eighth cranial nerves and the
solitary tract. The nerve to the stapedius mus-
internal auditory artery. The aperture on
cle and the main facial nerve trunk are
the cranial side is located at approximately
motor nerves originating from the facial
nucleus in the caudal pons. The chorda tym- the center of the posterior face of the pyra-
pani, like the greater superficial petrosal, mid of the temporal bone (see Fig. 2–1).
is a mixed nerve containing (1) parasym- Two other important orifices are in this
vicinity. Halfway between the canal and the
pathetic efferent fibers from the supe-
sigmoid sinus, the slit-like aperture of the
rior salivatory nucleus, destined for the
vestibular aqueduct contains the endolym-
sublingual glands, and (2) afferent taste
phatic sac, a structure important in the ex-
fibers from the anterior two-thirds of the
change of endolymph. The second open-
tongue, ending in the nucleus of the soli-
ing is that of the cochlear aqueduct, at the
tary tract.
same level as the auditory canal but on the
Knowledge of the structure and function
inferior side of the pyramid. The labyrin-
of each division of the facial nerve allows
thine opening of this channel is located in
the clinician to localize disease affecting the
the scala tympani, providing a connection
nerve within the temporal bone.7 Lesions
in the internal auditory canal commonly in- between the subarachnoid and the peri-
volve both the seventh and eighth cranial lymphatic spaces.
nerves. Lesions of the labyrinthine segment
of the facial nerve above the geniculate
MEMBRANOUS LABYRINTH
ganglion impair ipsilateral (1) lacrimation,
(2) stapedius reflex activity, (3) taste on The membranous labyrinth is enclosed
the anterior two-thirds of the tongue, and within the channels of the bony labyrinth
(4) facial muscular strength. A lesion of the (Fig. 2–5). A space containing perilym-
tympanic segment central to the nerve of phatic fluid, a supportive network of con-
the stapedius muscle affects only the latter nective tissue, and blood vessels lies be-
three functions (2–4) listed above, and a le- tween the periostium of the bony labyrinth
sion of the mastoid segment before the ori- and the membranous labyrinth; the spaces
gin of the chorda tympani affects only the within the membranous labyrinth contain
latter two (3, 4). Finally, a lesion at the sty- endolymphatic fluid. The endolymphatic
The Peripheral Vestibular System 29
Figure 2–6. The crista: (A) anatomy, (B) mechanism of hair cell activation with angular acceleration, and (C) ori-
entation of the semicircular canals within the head. AC, anterior canal; HC, horizontal canal; PC, posterior canal.
share a common opening on the posterior enlarges to form the ampulla. A crest-like
side of the utriculus. Precise measurement septum, the crista, crosses each ampulla in
of the planes of the canals, however, indi- a perpendicular direction to the longitudi-
cates that they are not aligned perfectly or- nal axis of the canal (Fig. 2–6 A, B). It rests
thogonal. All angular movements stimulate on the bone of the canal and consists of
at least two canals and often all three. sensory epithelium lying on a mound of
At the anterior opening of the horizon- connective tissue, where blood vessels and
tal and anterior canal and the inferior nerve fibers reach the sensory receptor
opening of the posterior canal, each tube area. Hair cells are located on the surface of
The Peripheral Vestibular System 31
the crista with their cilia protruding into the In the human vestibular organ, there are
cupula—a gelatinous mass of the same com- approximately 23,000 hair cells (type I and
position as that of the otolithic membrane. type II) in the three cristae and about 52,000
The cupula extends from the surface of the in the two macules.19,20 The number of neu-
crista to the ceiling of the ampulla, forming rons innervating the three cristae is approx-
what appears to be a watertight seal.9,12 imately 5700 and the two macules, approxi-
The hair cells within each crista are ori- mately 8600, for a total of approximately
ented so that their kinocilia are lined up on 14,300 nerve fibers.21 In the chinchilla, for
the same side of the cilia normal to the lon- which more accurate measurements are
gitudinal axis of the crista. In the vertical available, the number of hair cells (type I and
canals, the kinocilia are directed toward the type II) in the crista of the horizontal semi-
canal side of the ampulla—rostrally in the circular canal is about the same as the num-
anterior and caudally in the posterior semi- ber of supporting cells (about 5000 of each).
circular canal. In the horizontal canal they Although the density of hair cells varies
are directed medially toward the utricular across the surface of the crista, the ratio of
side (Fig. 2–6A). The opposing morpho- type I to type II hair cells is near 1 in all re-
logic polarization is the reason for the dif- gions (i.e., peripheral and central).16
ference in directional sensitivity between In recent years it has been shown that
the horizontal and vertical canals.13 The af- supporting cells can differentiate into new
ferent nerve fibers of the horizontal canals hair cells following destruction of the sen-
are stimulated by endolymph movement in sory epithelium This was initially seen in
the utricular or ampullopetal direction the cochlea of quail and chicken after
(Fig. 2–6B), while those of the vertical acoustic trauma22,23 and then in the cochlea
canals are stimulated by ampullofugal en- and vestibular labyrinth of mammals after
dolymph flow. As a physiological unit the drug ototoxic exposure (Fig. 2–8).17,24,25
three semicircular canals are capable of
codifying angular acceleration of the head
OTOLITHS
in a three-dimensional space.
In the vestibular organs of avians and The membranous labyrinth forms two glob-
mammals, there are two different types of ular cavities within the vestibule: the utricle
hair cells—type I and type II (Fig. 2–7, also and the saccule. The saccule lies on the
see Fig. 1–7). Type I hair cells are globular medial wall of the vestibule in a spherical
and are completely surrounded by a large recess inferior to the utricle with which it
calyx nerve terminal.14–18 The afferent is in contact but without direct connection.
fibers that give rise to these nerve calices It communicates with the endolymphatic
are among the largest in the body, meas- duct (and thus the utricular duct) by the
uring more than 20 m in diameter in saccular duct and with the cochlea by the
some lower animals and 10 m in humans. ductus reuniens (see Fig. 2–5). The sensory
Efferent nerves synapse on the outside sur- area of the saccule, the macule, is a
face of the calices. Type II hair cells are cylin- differentiated patch of membrane in the
drical and receive numerous small synap- medial wall, is hood shaped, and lies pre-
tic terminals from afferent and efferent dominantly in a vertical position (Fig. 2–9).
neurons.18 The hair cells are surrounded The utricular cavity is oval in shape, con-
by supporting cells whose top surface is cov- necting to the membranous semicircular
ered with microvilli. The supporting cells canals via five openings. The macule of the
extend the whole length of the sensory neu- utricle is located next to the anterior open-
roepithelium from the basal membrane to ing of the horizontal semicircular canal and
the surface. Their nuclei line up in a row lies mostly in a horizontal position in a
immediately above the basal membrane recess on the anterior part of the utricle.
(Fig. 2–7A). By contrast, the nuclei of the The utricle communicates by the utricular
hair cells are midway between the basal duct with the endolymphatic duct at the
membrane and the luminar surface. This same level as, but by different openings
pattern of nuclear organization is similar from, those of the saccular duct. Thus, the
throughout all vertebrates. endolymph in the superior or utricular part
Figure 2–7. Mammalian hair cells. (A, B) Photomicrographs of chinchilla crista (cross section). Long arrows,
type I hair cells; open arrows, type II hair cells; arrow heads, supporting cells, curved arrows, afferent nerve
fibers. B is an enlargement of the box outlined in A. Bar, 10 m. (C, D) Electron micrographs of type I and
type II hair cells from the chinchilla. Type I hair cells are surrounded by the chalice ending of an afferent
nerve fiber, whereas type II hair cells are contacted by afferent nerve boutons (arrows). SC, supporting cell.
Bar 1 m.
32
The Peripheral Vestibular System 33
Figure 2–8. Photomicrographs of the crista ampullaris from a chinchilla whose inner ears were implanted with
0.05 mg gentamicin. (A) At 7 days post-treatment there is almost complete obliteration of all sensory cells. No
type I hair cells are present, and most of the type II hair cells have disappeared. Supporting cell nuclei are nor-
mal in appearance and begin to migrate to the apical portion of the sensory epithelia (arrowheads). Most nerve
fibers have retracted out of the epithelium. (B) At 28 days after gentamicin treatment, type I hair cells surrounded
by growing nerve terminals (arrows) and type II hair cells (II) are easily identified. Supporting cell nuclei (arrow-
heads) are aligned at the base of the epithelia. Bar 40 m, toluidine blue. (Courtesy of Ivan Lopez, Los Ange-
les, California.)
of the labyrinth is separated from that of the at different angles, making the macule
saccule and cochlea by these tiny ducts. multidirectionally sensitive (Fig. 2–9C).
The surfaces of the utricular and saccu- Since the macules are located off-center
lar macules are covered by the otolithic mem- from the major axis of the head, they are
brane, which is a structure consisting of a subjected to tangential and centripetal
mesh of fibers embedded in a gel com- forces during angular head movements.
posed of acid mucopolysaccharides (Fig. The sensory organization of the macule
2–9A).26,27 This membrane contains a su- is different from that of the crista. Within
perficial calcareous deposit, the otoconia, each crista, all of the hair cells are oriented
which consist of small calcium carbonate in the same direction, making the crista
crystals, ranging from 0.5 to 30 m in di- easily capable of discriminating the direc-
ameter and having a density more than tion of rotation. In the macules, the hair
twice that of water.28 As discussed in Chap- cells on each side of the striola are oriented
ter 1, the stereocilia of the macular hair in the opposite directions (see Fig. 2–9 ).
cells protrude into the otolithic membrane. The global afferent output from each mac-
The striola is a distinctive curved zone run- ule is the combination of excitation on one
ning through the center of each macule side of the striola and inhibition of another
(see Fig. 2–9). The hair cells on each side set on its other side. The brain must de-
of the striola are oriented so that their code this complex combination of afferent
kinocilia point in opposite directions. In signals to determine the resultant direc-
the utricle the kinocilia face the striola, and tion of linear acceleration.
in the saccule they face away from it. As a
consequence, displacement of the macule’s
otolithic membrane in one direction has an Labyrinthine Fluids
opposite physiologic influence on the set of
hair cells on each side of the striola (Fig. Two separate fluid compartments exist
2–9B). Furthermore, because of the curva- within the inner ear: the perilymph and the
ture of the striola, hair cells are oriented endolymph. The compartments do not
34 Anatomy and Physiology
Figure 2–9. The macule: (A) anatomy, (B) mechanism of hair cell activation with static tilt, and (C) orientation
of saccular and utricular macules. Arrows indicate the direction that the kinocilia point toward. (Adapted from
Barber HO, Stockwell CW. Manual of Electronystagmography. CV Mosby, St. Louis, 1976.)
communicate and each has a different its inner ear opening at the base of the scala
chemical composition. tympani (Fig. 2–5). In most instances, this
channel is filled with a loose net of fibrous
tissue continuous with the arachnoid. The
DYNAMICS OF FLUID FORMATION
size of the bony canal varies from individual
The mechanism of formation of the inner to individual. Necropsy studies in patients
ear fluids is still not well understood. The who died of subarachnoid hemorrhage or
perilymph is, in part, a filtration of cere- meningitis have revealed free passage of
brospinal fluid (CSF) and, in part, a filtra- leukocytes and red blood cells into the inner
tion from blood vessels in the ear.29–32 The ear in some patients, whereas in others the
CSF communicates directly with the peri- cells were blocked from passing through the
lymphatic space through the cochlear aque- aqueduct.33,34 Blood cells have also been
duct, a narrow channel 3 to 4 mm long with found passing into the internal auditory
The Peripheral Vestibular System 35
canal and through the porous canaliculi normally is displaced outward. This is not
that contain the vestibular and cochlear the optimal position for the stapes since in
nerves, suggesting another route for CSF– animals, sound is transmitted more effec-
perilymph communication.33 Probably the tively after correcting for the dc pressure on
most important source of perilymph, how- the stapes. The benefit corresponds to 1 dB/
ever, is filtration from blood vessels within 1 ml of water for a maximum of about 10 dB.54
the perilymph space, since blocking the Destruction of the epithelium lining the
cochlear aqueduct does not appear to affect endolymphatic sac or occlusion of the duct
inner ear morphology or function.35,36 results in an increase of endolymphatic vol-
The main sites for the production of en- ume in experimental animals.36,55 The first
dolymph are the marginal cells of the stria change is an expansion of cochlear and sac-
vascularis of the cochlea and the dark cells of cular membranes, which may completely
the vestibular labyrinth.30–32,37 Endolymph fill the perilymphatic space. The anatomic
production is tightly coupled to K secre- changes resulting from this experiment are
tion.38 A Na-K-Cl cotransporter expressed in comparable to those found in the temporal
the basolateral membrane of marginal and bones of patients with Meniere’s syndrome
dark cells pumps K into these cells to high (either idiopathic or secondary to known
levels. Potassium channels at the apical sur- inflammatory disease).
face of the marginal and dark cells allow K
accumulating in the cells to flow back into
FLUID CHEMISTRY
the endolymph thus maintaining the high
K concentration and the generator poten- The chemical compositions of the fluids fill-
tial. In mice, mutations in the genes that code ing the inner ear are similar to those of
for the Na-K-Cl cotransporter protein or the the extracellular and intracellular fluids
apical K channel proteins lead to a failure throughout the body. The endolymphatic
to produce endolymph.39–41 system contains intracellular-like fluids with
Three theories have been proposed re- a high potassium and low sodium concen-
garding the regulation of endolymph vol- tration, whereas the perilymphatic fluid re-
ume. The longitudinal, or Guild, theory42 sembles the extracellular fluid with a low
assumes that endolymph is produced in the potassium and high sodium concentra-
cochlea and vestibular labyrinth and flows tion.45,56 Figure 2–5 shows the relationship
toward the endolymphatic sac where it is between electrolytes and protein concentra-
resorbed. The radial theory assumes a lo- tion of the different fluid compart-
cal transverse and active diffusion process ments.31,45,57 The high protein content in
between endolymph and perilymph.43 The the endolymphatic sac, compared with that
dynamic theory, a combination of the Guild in the rest of the endolymphatic space, is
and radial theories, assumes a radial ionic consistent with the sac’s role in the resorp-
diffusion process and a slow longitudinal tion of endolymph. The difference in pro-
bulk process.31,44,45 tein concentration between perilymph and
The pressure of the inner ear fluids has CSF argues against a free communication
been shown by direct measurements to be between the compartments of these two flu-
different from the atmospheric pressure of ids and in favor of an active process of per-
the middle ear.46–51 The perilymph and ilymph production. The electrolyte compo-
endolymph are both at an equal positive sition of the endolymph is critical for normal
pressure of approximately 7 to 10 cm of functioning of the sensory organs bathed in
H2O.46 When the pressure in the intracra- fluid. Rupture of the membranous labyrinth
nial cavity or the labyrinth increases to in experimental animals causes destruction
above normal, the pressure will tend to of the sensory and neural structures at the
equilibrate between the two compart- site of the endolymph–perilymph fistula.58
ments.52,53 The round window elasticity It is possible to sample the fluid in the
provides a measure of protection for pres- vestibule by introducing a micropipette
sure regulation in the inner ear.48 through a tiny fistula in the footplate of the
The positive pressure of the perilymph af- stapes.59,60 The fluid obtained normally has
fects the position of the stapes, which the chemical composition of perilymph given
36 Anatomy and Physiology
in Figure 2–5. In 29 patients with vestibular artery, the anterior vestibular branch, pro-
schwannomas, the protein content of the vides irrigation to the utricle and ampulla
perilymph was consistently elevated, with an of the anterior and horizontal semicircu-
average value of 1800 mg percent.60 Eleva- lar canals as well as some blood to a small
tion of perilymph protein can occur when portion of the saccule. The different
the protein content of CSF is normal or only sources of blood supply lead to independ-
slightly elevated. The electrolyte composition ent pathologic changes in cases of vascu-
of perilymph remains normal in such pa- lar abnormalities.
tients. In patients with Meniere’s syndrome, The anterior vestibular vein drains the
the markedly dilated sacculus or herniated utricle and the ampullae of the anterior and
cochlear duct is usually in contact with the horizontal canals; the posterior vestibular
footplate, so that endolymph rather than vein drains the saccule, the ampulla of the
perilymph is obtained from tapping the posterior canal, and the basal end of the
vestibule. The chemical composition of per- cochlea (Fig. 2–10B).63,64 The confluence of
ilymph obtained from other regions of the these veins and the vein of the round win-
labyrinth at the time of surgery is normal in dow becomes the vestibulocochlear vein.
patients with Meniere’s syndrome.60 Blood from the cochlea is carried primarily
by the common modiolar vein and, when
joined by the vestibulocochlear vein, be-
Blood Supply comes the vein at the cochlear aqueduct.
This large venous channel enters a bony
The artery that irrigates the membranous canal near the cochlear aqueduct to empty
labyrinth and its neural structures is a into the inferior petrosal sinus. The semi-
branch of an intracranial vessel and does not circular canals are drained by veins that pass
communicate with arteries in the otic cap- toward the utricle and form the vein of the
sule and the tympanic cavity.61,62 This ves- vestibular aqueduct, which accompanies the
sel usually originates from the anteroinfe- endolymphatic duct and drains into the lat-
rior cerebellar artery, but occasionally it eral venous sinus.
arises directly from the basilar artery or Blood flow (BF) from the arterioles to the
some of its branches. As it enters the tem- venules is determined by the ratio of the driv-
poral bone, it forms branches that irrigate ing force (F) to the resistance (R) of the
the ganglion cells, nerves, dura, and arach- walls such that BF F/R and the value of
noidal membranes in the internal auditory F is given by the blood pressure difference
canal.63,64 Shortly after entering the inner between the arterioles and the venules. The
ear, the labyrinthine artery divides into two value of R includes the wall resistance and
main branches: the common cochlear artery any outside pressure acting on the vessel
and the anterior vestibular artery (Fig. 2–10). walls. As in other organs, veins in the inner
Because the arteries course independently ear have lower R values than those of
within the canal, it is possible that alterations arterioles with intraluminar pressure of
in one branch result in changes only in the 5–20 cm H2O and will collapse or expand,
part of the inner ear to which it provides the depending on the value of F, with venules
blood supply. The common cochlear artery operating as effective blood reservoirs.
forms two branches: the posterior vestibu- However, when the pressure outside the
lar artery and the main cochlear artery. The venules becomes greater than the intra-
latter enters the central canal of the modi- venous pressure, R will increase and there
olus where it generates the radiating arte- will be a collapse of the walls, with impair-
rioles, forming a plexus within the cochlea ment of the blood flow. Experimental and
irrigating the spiral ganglion, the struc- clinical data corroborate the possibility
tures in the basilar membrane, and the stria of inducing ischemia and damage to the
vascularis. The posterior vestibular artery, sensory cells in the auditory and vestibular
a branch from the common cochlear ar- organs in combination or separately, either
tery, is the source of blood supply to the by occluding the vessels or increasing in-
inferior part of the saccule and the ampulla tralabyrinthine pressure.
of the posterior semicircular canal. The The physiological and anatomical effects
other primary branch of the labyrinthine of permanent and temporary ischemia
The Peripheral Vestibular System 37
Figure 2–10. Arterial (A) and venous (B) labyrinthine circulation. (From Schuknecht HF. Pathology of the Ear.
Harvard University Press, Cambridge, 1974, with permission.)
on the inner ear by occluding the inter- produce mixed functional and morpholog-
nal auditory artery have been extensively ical changes. Interfering with endolymph
studied.65–67 Cochlear function is affected circulation (experimental hydrops), and
within 15–30 sec but can recover even after thus increasing inner ear pressure, can im-
5–10 min of complete blood flow obstruc- pair labyrinthine blood flow.68–71
tion. If the dysfunction is of a longer dura-
tion, the damage is irreversible and associ-
ated with pathological inner ear changes, Innervation
including sensorineural degeneration and
even new bone formation destroying the in- The internal auditory canal is a tubular
ner ear spaces. Shorter intervals of ischemia excavation in the petrous portion of the
38 Anatomy and Physiology
temporal bone, measuring about 15 mm in superior group forming the superior divi-
length and 6 mm in width.72 The medial sion of the vestibular nerve and the inferior
end of the tube opens into the cerebellopon- forming the inferior division.74,75 The supe-
tine angle cistern; the lateral end is closed by rior division innervates the cristae of the an-
a thin bony plate, the lamina cribrosa. terior and horizontal canals, the macule of
Through tiny perforations in the lamina the utricle, and the anterosuperior part of
cribrosa, the afferent and efferent vestibu- the saccular macule. It leaves the internal au-
lar and cochlear nerve fiber endings pass ditory canal through the posterosuperior
into the labyrinthine cavity to contact the fossa of the lamina cribrosa. The inferior di-
sensory organs. The lamina cribrosa is di- vision innervates the crista of the posterior
vided into an upper and a lower section by canal and the main portion of the macule of
the crista falciformis; each of these halves is the saccule and leaves the internal auditory
in turn divided by vertical bony cristae into canal through the posteroinferior area of the
an anterior and a posterior section. The au- lamina.
ditory nerve, consisting of approximately Detailed study of the vestibular nerve in
30,000 fibers, occupies the anteroinferior animals reveals a highly organized arrange-
part of the internal auditory canal, and ment of the nerve fibers originating from
the vestibular nerve, containing approxi- the different inner ear receptors and from
mately 15,000 fibers, occupies the posterior the two types of hair cells within each
half.21,73 The facial nerve is located in the receptor.21,76–78 There is a similar uni-
remaining anterosuperior quadrant. modal distribution of primary afferent neu-
The afferent bipolar ganglion cells of the rons with regard to axon and cell body di-
vestibular nerve (Scarpa’s ganglion) are ameter in several species studied (Fig.
arranged in two cell masses in a vertical col- 2–11). For example, small fibers (2.5 m)
umn within the internal auditory canal—the project preferentially to the periphery of
Figure 2–11. Distribution of primary afferent fibers of different diameters (including myelin) within the cristae
of humans, monkeys, and chinchillas. The smallest fibers (2.5 m) are concentrated in the periphery while the
largest fibers ( 4.5 m) are more numerous at the center of the cristae. Intermediate-size fibers tend to be
equally distributed throughout the cristae.
The Peripheral Vestibular System 39
the sensory epithelium whereas larger ones have a preponderance of thin fibers (Fig.
( 4.5 m) project to the center. 2–12A, inset).
The highly organized innervation of The bundles of fibers that innervate a
the crista in the chinchilla is shown in discrete area of the crista travel together to-
Figure 2–12.79 Underneath the sensory or- ward the nervous system and, in all prob-
gan, the main nerve divides into two smaller ability, innervate groups of neighboring
ones. Each of the two nerve branches in- neurons in the vestibular nuclei. There ap-
nervates half of the crista and thus half of pears to be a topographical representation
the hair cells. Within half a millimeter from of the vestibular end-organ in the CNS that
the sensory epithelium, each nerve divides is comparable to the topographical projec-
into 8 to 10 bundles of fibers that align in tion of different parts in the basilar mem-
two rows, one for each slope of the crista. brane of the cochlea to the auditory nuclei.
Among these smaller bundles, those that in- Each of the afferent bundles contain-
nervate the center of the crista have a ing fibers of different diameters—thick,
greater proportion of thick fibers whereas medium and thin—is derived from the same
the bundles that innervate the periphery restricted area of about 0.2 mm2 on the
40 Anatomy and Physiology
Figure 2–13. Different types of primary afferent nerve endings labeled by intracellular injection of horserad-
ish peroxidase. Reconstructions of two calyx units with simple (a) and complex (b) endings, a dimorphic unit
(c), and a bouton unit (d), all taken from a single horizontal canal crista, are shown. The points at which the
parent axons of labeled afferents enter the sensory epithelium are indicated on a standard surface recon-
struction (center). Bar 10 m. (From Fernandez C, et al. The vestibular nerve of the chinchilla. 1. Periph-
eral innervation patterns in the horizontal and superior semicircular canals. J Neurophysiol 1988;60:167, with
permission.)
crista and carries information about local- few hair cells with caliceal endings (type I)
ized cupula movement. in the center (Fig. 2–13).80,81 Neurons
Classical morphologists identified three with intermediate-size axon diameters
types of nerve endings in the receptors: (2.3 0.6 m) have both bouton and cal-
large-diameter fibers had caliceal endings, iceal endings and are more or less evenly
small-diameter fibers had bouton endings, distributed throughout the crista. Neurons
and intermediate-size fibers had both with small axon diameters (1.4 0.4 m)
types of ending.74 With recently devel- have only bouton endings and innervate
oped techniques for labeling individual multiple type II hair cells predominantly
neurons and fibers by intracellular injec- in the periphery. Of a sample of 368
tion of horseradish peroxidase, detailed fibers, 40 (11.1%) were calyx units, 79
information has been obtained in the chin- (21.5%) were bouton units, and 248
chilla regarding the association of fiber (67.4%) were dimorphic units. Approxi-
diameter size with different nerve end- mately the same distribution of fibers ac-
ings in different parts of the receptors. In cording to diameter size is seen in the
the crista, neurons with large axon diam- crista of the squirrel monkey and in hu-
eters (2.8 0.6 m) innervate one or a mans (Fig. 2–11).
The Peripheral Vestibular System 41
In the macules, as in the cristae, the di- inhibits spontaneous and evoked activity in
ameter of the nerve fibers has a unimodal the afferent nerve from the skate semicir-
distribution.82 Fibers of large diameter with cular canal ampulla94 and iontophoretic
only caliceal endings predominate near the application of GABA increases the sponta-
striola whereas the thinner fibers innervate neous activity of single units in the saccu-
the periphery. Fibers of intermediate di- lar macule of the cat.95 This effect is likely
ameter (dimorphic) are distributed evenly presynaptic in origin, however, and not due
throughout the macule. In the chinchilla to the activation of postsynaptic GABA re-
macule, as in the crista, dimorphic units ceptors on the vestibular nerve. Acetyl-
outnumber caliceal units by 3 to 1. Caliceal choline (ACh) is the likely efferent neuro-
units typically innervate more hair cells transmitter within the vertebrate vestibule.96
(10–40) than dimorphic units (5–20). Histochemical staining techniques have
Peripheral vestibular efferent fibers orig- identified the presence of acetylcholin-
inate from approximately 300 neurons lo- esterase at the vestibular receptor neural
cated bilaterally ventromedial to the ventral junction in the cat and this staining is lost
portion of the lateral vestibular nucleus.83 after vestibular nerve section.97 Choline
These fibers accompany the cochlear effer- acetyltransferase activity in homogenates of
ent fibers (the so-called olivocochlear bun- the frog labyrinth markedly decreases after
dle) in the vestibular nerve trunk as far as vestibular nerve transection.92 This ACh-
the saccular ganglion, at which point the two mediated efferent system is thought to pro-
efferent systems diverge almost at right an- vide a tonic inhibitory influence upon the
gles to each other. Vestibular efferent fibers afferent activity arising from the vestibular
join each division of the vestibular nerve and receptor.98–100
run to each macule and crista. Here they
end as vesiculated boutons containing many
small homogeneous vesicles (see Fig. 1–7). Physiology of Vestibular
One efferent fiber gives off numerous bou- End-organs
tons that will synapse either directly on hair
cells or onto their afferent nerve endings. SEMICIRCULAR CANALS
Neurotransmission within the vestibular
Background
sensory organs (both afferent and efferent)
is chemical in nature. Although several The functional role of the semicircular canals
chemicals have been implicated in the neu- was first linked to their gross anatomic fea-
rotransmission at the hair cell–afferent tures by Flourens in 1842.101 While study-
nerve junction, a glutamate-like substance ing the auditory labyrinth in pigeons, he
is the most likely excitatory neurotransmit- noted that opening a semicircular canal re-
ter.84,85 Glutamate or related excitatory sulted in characteristic head movements in
amino acids increase the spontaneous and the plane of that canal. Several subsequent
stimulus-evoked firing of vestibular neu- investigators proposed that movement of en-
rons in the frog86,87 and the cat.88 The ef- dolymphatic fluid within the canal was re-
fect is reversibly blocked by the application sponsible for excitation of the cristae.102–104
of a competitive non–N-methyl-D-aspartate It was not until the studies of Ewald in 1892,
(NMDA) receptor agonist; this finding however, that a clear relationship was estab-
suggests that the
-amino-3-hydroxy-5- lished between the planes of the semicircu-
methyl-4-isoxazole-proprionic acid (AMPA) lar canals, the direction of endolymph flow,
receptor is the receptor subtype activated and the direction of induced eye and head
at the afferent nerve terminal.89,90 Both movements.105 Exposing the membranous
NMDA and non-NMDA receptors are also labyrinth of the semicircular canals of pi-
probably present on hair cells, providing a geons, Ewald applied positive and negative
feedback mechanism to modulate the ac- pressure to each canal membrane to cause
tivity of hair cells.84 Gamma-aminobuteric ampullopetal and ampullofugal endolymph
acid (GABA) also appears to be a neuro- flow. Three important observations, which
transmitter in the inner ear.91–93 Picro- became known as Ewald’s laws, were (1) the
toxin, a known GABA receptor blocker, eye and head movements always occurred in