Understanding Benign Paroxysmal Positional Vertigo Francesco Dispenza, Alessandro De Stefano
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Anatomy and Physiology of the Posterior LabyrinthChapter 1

Mercedes FS Araújo,
André LL Sampaio,
Carlos A Oliveira
The membranous labyrinth arises from a vesicle that separates from the rhombencephalus in the embryo called the otocyst. This vesicle differentiates into the organs of the labyrinth: utricle, saccule, semicircular canals, and cochlea. The bony labyrinth is formed by the mesenchime surrounding the membranous labyrinth that becomes the petrous portion of the temporal bone. The bony labyrinth is therefore the hard bones that encase the membranous labyrinth and protect these structures.
Semicircular Canals
The vestibular system is the system of balance and equilibrium. It consists of five distinct sensory organs: three semicircular canals (SCCs) that are sensitive to angular accelerations (head rotations) and two otolithic organs (saccule and utricle) that are sensitive to linear accelerations (such as motion in a vehicle or an elevator). Thus, the function of the vestibular system is to sense motion of the head and to codify these movements precisely to the central nervous system (CNS).
The bony labyrinth consists of three SCCs, the cochlea, and a central chamber called the vestibule (Fig. 1.1). The bony labyrinth is filled with perilymphatic fluid that has a composition similar to that of cerebrospinal fluid (high Na:K ratio). Perilymphatic fluid communicates via the cochlear aqueduct with cerebrospinal fluid. Because of this communication, disorders that affect spinal fluid pressure (such as lumbar puncture) can also affect inner ear function (Fig. 1.2). The membranous labyrinth is suspended within the bony labyrinth by perilymphatic fluid and supportive connective tissue. It contains five sensory organs: the membranous portions of the three SCCs and the two otolithic organs, the utricle and saccule. Note that one end of each canal is widened in diameter to form an ampulla. The ampula is where the cristae of the SCCs are located. The membranous labyrinth is filled with endolymph (Fig. 1.1).2
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Fig. 1.1: The osseous and membranous labyrinth.
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Fig. 1.2: Spatial organization of the semicircular canals.
3In contrast to perilymph, the endolymph resembles intracellular fluid in electrolyte composition (high K:Na ratio). Under normal circumstances, there is no direct communication between the endolymph and perilymph compartments.
This section will describe the anatomic basis for the labyrinth functions. The membranous labyrinth is surrounded by the bone labyrinth of the petrous bone and is immersed in perilymph. Active transport works in order to keep differences in ions concentrations between the external perilymph and the internal endolymph.
The SCCs are membranous structures with an enlargement at the utricular end, the ampulla. A gelatinous flap completely seals one side of ampulla from the other side. The ampulla is elastic and any pressure difference across it will be detected. The membranous SCCs begin and end in the utricle. There is therefore an ampulated end and a nonampulated one. The special dispositions of these structures are fundamental for the posterior labyrinth function.
The SCCs are arranged as a set of three orthogonal sensors (see Fig. 1.2); that is, each canal is at approximately right angles to the other two. Furthermore, each canal is maximally sensitive to rotations that lie in the plane of that canal. The result of this arrangement is that the three canals can uniquely specify the direction and amplitude of any arbitrary head rotation. Each of the canals acts as an integrating accelerometer; thus, the necessary stimulus for the canal is an angular acceleration, but the information that is encoded by the firing of the afferent nerve fiber is more closely related to angular velocity. Finally, the canals are organized into functional pairs wherein both members of the pair lie in the same plane. Any rotation in that plane will be excitatory to one of the members of the pair and inhibitory to the other. Although in the horizontal system the two horizontal canals form a functional pair, the situation is somewhat more complex in the vertical system. Here, the anterior canal on one side is parallel and coplanar with the posterior canal on the opposite side. For example, the right anterior canal and the left posterior canal form a functional pair. Thus, when the head is turned, the membranous labyrinth moves with it but the endolymph inside has an inertial effect and that tends to oppose the turning movement.
Because the primary vestibular afferent fibers exhibit a substantial resting firing rate (60–80 spikes per second in mammals), each canal is able to report rotations in either its excitatory direction (by increasing its firing rate) or its inhibitory direction (by decreasing). This observation explains why it is possible to function reasonably well after the loss of one labyrinth.
The vestibular system forms the basis for a number of rather fundamental reflexes: the vestibulocollic reflex (VCR; head stabilization), the 4vestibulospinal reflex (VSR; control of upright posture), and the vestibulo-ocular reflex (VOR; retinal image stabilization). The last of these, the VOR, has been studied far more extensively than the others and is certainly the best understood; it is this reflex that forms the basis for most clinical testing (calorics, rotation tests, etc.).
This chapter describes the anatomy of the VOR in detail but without exploring every possible aspect. Many of the details that will be described have been obtained from experiments in animal species, particularly the cat and monkey; nevertheless, the information is certainly applicable to humans because the vestibular system has changed very little during the evolution of vertebrates.
Otolith Organs—the Saccule and the Utricle
The otolith organs located in the vestibule of the osseous labyrinth register forces related to linear acceleration. They respond to both linear head motion and with change of the gravitational axis. The function of the otolithic organs is illustrated by the situation of a passenger in a commercial jet. During flight at a constant velocity, the passenger has no sense that he is traveling at 300 miles/h. However, in the process of taking off and ascending to cruising altitude, he senses the change in velocity acceleration as well as the tilt of the plane on ascent. The otolithic organs respond better to changes in acceleration than in velocity.
The sensory part of the otolithic organs named secular, and utricular maculae are covered by crystals of calcium carbonate (otoliths) in gelatinous amorphous material that tops the maculae of saccule and utricle.
Like the canals, the otoliths are arranged to enable them to respond to motion in all three dimensions (Fig. 1.3). However, unlike the canals, which have one sensory organ per axis of angular motion, the otoliths have only two sensory organs for three axes of linear motion. In an upright individual, the saccule is vertical (parasagittal), whereas the utricle is horizontally oriented (near the plane of the lateral SCCs). In this posture, the saccule can sense linear acceleration in its plane, which includes the acceleration oriented along the occipitocaudal axis as well as linear motion along the anterior-posterior axis. The utricle senses acceleration in its plane, which includes lateral accelerations along the interaural axis as well as anterior-posterior motion.
The earth's gravitational field is a linear acceleration field, so in a person on the earth, the otoliths register tilt. For example, as the head is tilted laterally (which is also called roll; Fig. 1.3), shear force is exerted upon the utricle, causing excitation, but shear force is lessened upon the saccule. Similar changes occur when the head is tilted forward or backward.5
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Fig. 1.3: Spatial organization of the saccule and utricle.
Because linear acceleration can come from two sources—earth's gravitational field and linear motion—there is a sensor ambiguity problem. We discuss strategies that the CNS might use to solve this problem later in the section on higher-level vestibular processing. In the otoliths, as in the canals, there is redundancy, with similar sensors on both sides of the head. Push-pull processing for the otoliths is also incorporated into the geometry of each of the otolithic membranes. Within each otolithic macula, a curving zone, the striata, separates the direction of hair-cell polarization on each side. Consequently, head increases afferent discharge from one part of a macula, while reducing the afferent discharge from another 6portion of the same macula. This extra level of redundancy in comparison with the SCCs probably makes the otoliths less vulnerable to unilateral vestibular lesions. Tilt increases afferent discharge from one part of a macula, while reducing the afferent discharge from another portion of the same macula. This extra level of redundancy in comparison with the SCCs probably makes the otoliths less vulnerable to unilateral vestibular lesions.
Blood Supply
The labyrinthine artery supplies the peripheral vestibular system (Fig. 1.4). The labyrinthine artery has a variable origin. Most often it is a branch of the anterior-inferior cerebellar artery (AICA), but occasionally a direct branch from the basilar artery may exist. Upon entering the inner ear, the labyrinthine artery divides into common cochlear artery and anterior vestibular artery. The anterior vestibular artery supplies the vestibular nerve, most part of the utricle, the ampulla of the anterior and lateral SCC. The cochlear artery divides into two branches, the main branch cochlear artery and the vestibulocochlear artery. The cochlear artery supplies the cochlea and the vestibulocochlear branch supplies part of the cochlea axis as well as the saccule and the ampulla of posterior SCC.
Vestibular Nerve
Vestibular nerve fibers are the afferent projections from the bipolar neurons of Scarpa's (vestibular) ganglion.
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Fig. 1.4: Vascular supply of the labyrinth.
7The vestibular nerve transmits afferent signals from the labyrinths along its course through the internal auditory canal (IAC). In addition to the vestibular nerve, the IAC contains the cochlear nerve (hearing), the facial nerve, the nervus intermedius (a branch of the facial nerve which carries sensation), and the labyrinthine artery.
The IAC travels through the petrous portion of the temporal bone to open into the posterior fossa at the level of the pons. The vestibular nerve enters the brainstem at the pontomedullary junction. Because the vestibular nerve is interposed between the labyrinth and the brainstem, some authorities consider this nerve a peripheral structure, whereas others consider it a central structure. We consider it a peripheral structure.
There are two patterns of firing in vestibular afferent neurons. Regular afferents usually have a tonic rate and little variability in interspike intervals. Irregular afferents often show no firing at rest and, when stimulated by head motion, develop highly variable interspike intervals.
Regular afferents appear to be the most important type for the VOR, because in experimental animals irregular afferents can be ablated without much change in the VOR. However, irregular afferents may be important for the VSR and in coordinating responses between the otoliths and canals.
Regular afferents of the monkey have tonic firing rates of about 90 spikes per second and a sensitivity to head velocity of about 0.5 spikes per degree per second. We can speculate about what happens immediately after a sudden change in head velocity. Humans can easily move their heads at velocities exceeding 300° per second. As noted previously the SCCs are connected in a push-pull arrangement so that one side is always being inhibited while the other is being excited.
Given the sensitivity and tonic rate noted previously, the vestibular nerve, which is being inhibited, should be driven to a firing rate of 0 spikes per second, for head velocities of only 180° per second! In other words, head velocities >180° per second may be unquantifiable by half of the vestibular system. This cutoff behavior has been advanced as the explanation for Ewald's second law, which says that responses to rotations that excite a canal are greater than those to rotations that inhibit a canal. Cutoff behavior explains why a patient with unilateral vestibular loss avoids head motion toward the side of the lesion.
Vestibular Nuclei
The vestibular nuclei consist of four major nuclei, superior, descending, lateral and medial and at least more seven minor structures. The superior and medial vestibular nuclei relate to the VOR. The lateral vestibular nucleus is primary involved in the VSR. All vestibular nuclei complex is located in the medulla oblongata on the brainstem.8
Endolymphatic Duct and Endolymphatic Sac
As shown in Figure 1.1, the endolymphatic duct comes out of the utricle, traverses the petrous bone toward the posterior fossa, and ends in the endolymphatic sac that lies in the posterior surface of the petrous bone in the posterior fossa. These structures have no function related to equilibrium and probably are related to endolymph absorption. In other words, there is a longitudinal flow of endolymph toward the endolymphatic sac where this fluid is resorbed. Dysfunction of the endolymphatic sac is believed to cause endolymphatic hydrops.
The vestibular system's main function is to sense head movements, especially involuntary ones, and counter them with reflexive eye movements and postural adjustments that keep the visual world stable and keep us from falling. The posterior labyrinth senses head rotation and linear acceleration and sends that information to secondary vestibular neurons in the brainstem vestibular nuclei. Information above the tonic (spontaneous) firing of the type I hair cells transmitted along type I neurons is largely thought to have a stimulatory effect in contrast to a more inhibitory effect attributable to type II hair cells and type II neurons.
The reflexive nature of the vestibular system is essential for complete understanding of vestibular physiology. The brainstem interprets imbalances in vestibular input due to pathologic processes in the same way that it interprets imbalances due to physiologic stimuli. Therefore, the cardinal signs of vestibular disorders are eye movement's reflexes and postural changes. These reflexes can largely be understood as the brainstem's responses to perceived rotation around a specific axis or perceived tilting or translation of the head. Knowing the effective stimulus for each vestibular end organ allows determination of which end organ or combination of end organs must be stimulated to produce the observed motor output. Specifically, neurons encoding head movement form synapses within the ocular motor nuclei to elicit the patterns of extraocular muscle contraction and relaxation needed for the VOR (Fig. 1.5), which stabilizes gaze (eye position in space). Other secondary vestibular neurons synapse on cervical spinal motor neurons to generate the VCR or to lower spinal motor neurons to generate the VSRs. These reflexes stabilize posture and facilitate gait. Vestibular sensory input to autonomic centers, particularly information about posture with respect to gravity, is used to adjust hemodynamic reflexes to maintain cerebral perfusion.9
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Fig. 1.5: Vestibulo-ocular reflex (VOR): when a rotational head movement is detected an inhibitory signal is triggered to extraocular muscles on one side and excitatory signal to the muscles on the other side producing compensatory eyes movement.
Finally, vestibular input to the cerebellum is essential for coordination and adaptation of vestibular reflexes when changes occur such as injury to a vestibular end organ or alteration in vision (e.g. a new pair of glasses).
The sequence of events that occur during the excitation of vestibular nerve fibers is very similar to auditory system, so stereocilia deflection is the common mechanism by which vestibular hair cells transduce mechanical forces into action potentials. Movements of the head or changes in linear acceleration cause deflection of the cupula (Fig. 1.6B) or shift the gelatinous matrix of the otolithic organs with its load of otolithic crystals (Fig. 1.7B) that will result in depolarization (stimulation) or hyperpolarization (inhibition) of types I and II hair cells. When the head tilts forward the gravitational force on the otolithic membrane of the otolithic organs changes and the hair cells are subjected to a new force that displaces cilia to the side; pulls them down, away from the epithelium in the inverted position or pushes them back against the cell in the upright position. It is observed the maximal discharge of the nerve when the cilia are bent to one side and minimal when they bent to the other side. At intermediate positions there is intermediate response.
Displacement of the stereocilia either toward or away from the kinocilium influences calcium influx mechanisms at the apex of the cell that causes the release or reduction of neurotransmitters from the cell to the surrounding afferent neurons.10
Semicircular Canals
The semicircular canals appear to be responsible for the equal but opposite corresponding eye-to-head movements that are commonly known as VOR, and they are primarily responsible by the sense of rotational acceleration of the head. The VOR is the most important human vestibular pathway and it is required to maintain a stable retinal image with active head movement. In order to ultimately produce conjugate versional VOR-mediated movements of the eyes, each vestibular nucleus receives electrical information from both sides that is exchanged via the vestibular commissure in the brainstem (Fig. 1.5). The organization is generally believed to be specific across the commissure. For example, neurons in the right vestibular nucleus that receive type I input from the right horizontal SCC project across commissure to the neurons found in the left vestibular nucleus that are driven by the left horizontal SCC receiving contralateral type II input and vice versa as described by Leigh and Zee.1 The VOR is subserved by a simple three-neuron pathway: motions detected by the end organ are transduced into neural impulses that are sent via the vestibular nerve to the vestibular nuclei and rostrally through the ascending medial longitudinal fasciculus (MLF) to the oculomotor nuclei of the extraocular muscles. Secondary vestibulo-ocular connections via the reticular formation have been described, but functionally these are less important than the direct three-neuron MLF vestibulo-ocular pathway. Inhibitory-crossed connections at the levels of both vestibular and oculomotor nuclei probably also participate in the VOR. The crossed-inhibitory oculomotor connections subserve antagonistic extraocular muscles that are important in the formation of conjugate-eye movements.2
Sensation by SCCs works as follows. When angular acceleration in the plane of an SCC starts, inertia causes the endolymph in the canal to lag behind the motion of the membranous canal, much as coffee in a mug initially remains in place as the mug is rotated about it. Relative to the canal walls, the endolymph effectively moves in the opposite direction as the head. Inside the ampulla, a swelling at the end of the canal where it meets the utricle, pressure exerted by endolymph deflects the cupula, an elastic membrane that spans a cross section of the ampulla (Fig. 1.6A). Once the vestibular hair cells are arrayed beneath the cupula on the surface of the crista ampullaris and its stereociliary bundles are coupled to the cupula its deflection creates a shearing stress between the stereocilia and the cuticular plates at the tops of the hair cells.
Stereocilia within a bundle are linked to one another by protein strands called “tip links” that span from the side of a taller stereocilium to the tip of its shorter neighbor in the array.11
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Figs. 1.6A and B: (A) The cupula spans the lumen of the ampulla from the crista to the membranous labyrinth at resting position. (B) If head moves to right, the relative flow of endolymph in the canal is therefore opposite to the direction of head acceleration. This flow produces a pressure across the elastic cupula, which suffers deflection.
The tip links are believed to act as gating springs for mechanically sensitive ion channels, meaning that the tip links literally tug at molecular gates in the stereocilia.3 These gates, which are cation channels, open or close (or, more precisely, spend more or less time in the open state), depending on the direction in which the stereocilia are deflected. When deflected in the open or “on” direction, which is toward the tallest stereocilium, cations, including potassium ions from the potassium-rich endolymph, rush in through the gates, and the membrane potential of the hair cell becomes more positive. This in turn activates voltage-sensitive calcium channels at the basolateral aspect of the hair cell, and an influx of calcium leads to an increase in the release of excitatory neurotransmitters, principally glutamate, from hair cell synapses onto the vestibular primary afferents. All of the hair cells on an SCC crista are oriented or “polarized” in the same direction. That is to say that their stereociliary bundles all have the tall ends pointing the same way, so that the endolymph motion that is excitatory for one hair cell will be excitatory for all of the hair cells on that crista.
Head rotation carries the membranous SCC along with it, whereas the inertia of the endolymph and cupula tend to keep these elements stationary in space (like the coffee in a mug as the mug is quickly turned). 12Nevertheless, two things act to accelerate the endolymph in the same direction that the head is turning but through the smaller angle. The first is the elastic or spring-like push from the distended cupula, as it pushes against the endolymph. The second is the viscous drag exerted on the endolymph at its interface with the walls of the membranous canal.
The movement of the cupula can now be described as a function of head acceleration: during a constant, low-acceleration head rotation, cupular deflection eventually reaches a steady-state constant value. The time course of cupular displacement, in response to a constant acceleration approximates a single exponential growth, and the time constant with which cupular displacement reaches its maximum deflection is approximately 10 seconds, the time constant of the cupula. When the constant acceleration stops, the cupula returns to its zero position exponentially with the same time constant. The same time constant governs the cupular response to very brief pulses of head acceleration. Such “velocity steps” are often done as part of clinical rotary chair tests. However, the measured value of the time constant of the VOR in such testing is generally much longer than what would be anticipated by this calculated cupular response because of further processing by the brain. During sinusoidal head rotations in the range encompassing most natural head movements (∼0.1–15 Hz), viscous friction dominates the cupular response, making cupular deflection proportional to head velocity.
Otolithic Organs
The otolithic organs (utricule and saccule) are primarily responsible for ocular counter-rolling with tilts of the head and for VSRs that help in the maintenance of body posture and muscle tone by sensing linear acceleration in horizontal and vertical (superoinferior) directions. These organs contain sheets of hair cells on a sensory epithelium called a macula. A gelatinous membrane sits atop the macula, and microscopic stones made of calcium carbonate, the otoliths (or otoconia), are embedded on the surface of this otolithic membrane. The sacculus (or saccule), located on the medial wall of the vestibule of the labyrinth in the spherical recess, has its macula oriented vertically. Gravity therefore tonically pulls the saccular otolithic mass inferiorly when the head is upright (Fig. 1.7A). The utriculus (or utricle) is located above the saccule in the elliptical recess of the vestibule. Its macula is oriented in roughly the same plane as the horizontal SCC, although its anterior end curves upward. When the head tilts out of the upright position (Fig. 1.7B), the component of the gravitational vector that is tangential to the macula creates a shearing force on stereocilia of utricular hair cells. The cellular transduction process is identical to that described above for the crista.13
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Figs. 1.7A and B: (A) Otolithic organ when head is upright. (B) Otoliths displacement when head is tilted.
However, the hair cells of the maculae, unlike those of the cristae, are not all polarized in the same direction. Instead, they are oriented relative to a curving central zone known as the striola. The utricular striola forms a C shape, with the open side pointing medially. The striola divides the utricular macula into a medial two-thirds (polarized to be excited by downward tilt of the ipsilateral ear) and a lateral one-third polarized in the opposite direction. Hair cells of the sacculus point away from its striola, which curves and hooks superiorly in its anterior portion. Each macula is essentially a linear accelerometer, with the saccular macula encoding acceleration roughly within a parasagittal plane (along the naso-occipital and superoinferior axes), and the utricular macula encoding linear acceleration roughly in an axial plane (along the naso-occipital and interaural axes). A given linear acceleration may produce a complex pattern of excitation and inhibition across the two maculas, a pattern that encodes the direction and magnitude of the linear acceleration.4 By contrast, each of the three SCCs senses just a one-dimensional component of rotational acceleration. Modulation of neurotransmitter release from hair cells within each vestibular end organ modulates the action potential frequency, or firing rate, of vestibular nerve afferent fibers. The afferents have a baseline rate of firing, probably due to a baseline rate of release of neurotransmitter from the vestibular hair cells. Changes in vestibular nerve afferent firing are conveyed to secondary neurons in the brainstem. Baseline firing gives the system the important property of bidirectional sensitivity: firing can increase for excitatory head movements and decrease for inhibitory head movements.5 Thus, loss of one labyrinth does not mean loss of the ability to sense one half of the head's movements.
It is common explaining movement of otoconial membrane by using the same analysis of cupular motion, but since the otoconial membrane is an inhomogeneous structure whose complexities make it very difficult to estimate the physical parameters in the model that would predict its responses under different conditions. The membrane consists of the 14dense otoconial layer on top, a stiff mesh layer in the middle, and an elastic gel layer on the bottom. At the macular surface, it is presumably fixed. It is unclear how tightly otoconial displacement is coupled to the motion of the stereocilia. These uncertainties lead to models that variously predict that the otoconial membrane responds to linear acceleration or velocity, but the actual behavior remains unresolved.6
Afferent Function
In mammals, physiologic response characteristics segregate vestibular nerve afferent fibers into two classes based on the regularity in the spacing of spontaneous action potentials.7 Regular afferents fire at 50–100 spikes/second at rest, with very little variation in resting rate for a given fiber. In general, they respond to vestibular stimulation with tonic responses. That is, their firing modulates about the baseline, going up and down in close approximation to the stimulus (linear acceleration for the otolith organs and rotational velocity for SCCs).
Considering morphologic differences between regular and irregular vestibular afferents, they have also different action mechanisms. Irregular afferents have a wider range of spontaneous rates than do regular fibers. Irregular units show phasic responses to the stimulus acting on the end organ. That is, the response is more transient, and it approximates the rate of change of the stimulus acting on the end organ rather than simply the stimulus itself. Irregular units may have very high sensitivity to vestibular stimuli, except for a unique group of low-sensitivity calyx units in the crista, whose function is still unclear. Sensitivities to activation by efferent pathways and to galvanic stimulation also are generally greater for irregular afferents. After the peak of an action potential (caused by inward sodium currents), outward potassium currents briefly hyperpolarize the vestibular afferent membrane. The potassium conductance decays in a time-dependent manner, and the membrane potential rises again toward the threshold voltage for spike generation. Excitatory postsynaptic potentials (EPSPs) due to synaptic neurotransmitter release superimpose on this repolarization. The model assumes that variations in this potassium conductance between different afferents accounts for their regularity of discharge. In regularly discharging afferents, the model proposes that a large potassium conductance decays slowly but inexorably, so that the repolarization continues in a deterministic fashion until the membrane potential again reaches firing threshold. The model assumes that quanta of neurotransmitter released from hair cells cause relatively little variation in the trajectory of the repolarization. This deterministic nature of the repolarization means that the membrane reaches the threshold for another spike at almost the same time for each spike. Thus, the interspike intervals are all similar, and the unit's discharge is regular.15
By contrast, in irregularly discharging afferents, the model assumes a potassium conductance that is high initially but decays rapidly so that it does not carry the membrane potential back up to the threshold for firing by itself. These fibers sit just below threshold voltage until driven above it by the added potential due to EPSPs. Neurotransmitter release and EPSPs are quantal and random, so that the time at which the membrane reaches firing potential is highly variable from spike to spike. Thus, the unit's discharge is irregular.
The difference about morphology and biochemistry of their membranes may be the origin of different firing characteristics between classes of afferents. They are different anatomically too: irregular units arise from the central zone of the crista or striola of the macula, and regular units arise from the peripheral zone of the crista or extrastriola of the macula. Because regular and irregular vestibular nerve afferent fibers have distinct characteristics in so many respects, it seems likely that they mediate different functions. One hypothesis holds that regular and irregular afferents may help compensate for different dynamic loads of the different vestibular reflexes.
Anatomically, regular and irregular afferents overlap extensively in their distributions to the central vestibular nuclei.8a,b However, physiologic evidence suggests that there is some segregation of regular and irregular inputs between central projections to the ocular motor centers and the spinal motor centers. Another role for the irregular afferents may be to initiate the vestibular reflexes with a very short latency for rapid head movements.9 Finally, some evidence suggests that the dynamics of irregular afferents are better suited to provide the modifiable component of the VOR when gain must be changed rapidly. In addition to >10,000 afferents, each labyrinth also receives efferent innervation from ∼400–600 neurons that lie on either side of the brainstem adjacent to the vestibular nuclei.10,11 In mammals, excitation of efferents causes an increase in the background discharge of vestibular afferents, particularly irregular ones. It is hypothesized that the efferents may serve to raise baseline afferent firing rates, particularly of irregular afferents, in anticipation of rapid head movements so as to prevent inhibitory silencing. Yet Cullen and Minor12 hypothesized that vestibular efferents may act to balance firing between the two labyrinths, a role that may be particularly important after some degree of loss of unilateral function.
The anatomic basis of SCCs physiology began with Flourens and Mach that described eye or head movements in the plane of a specific semicircular canal when it was manipulated in an isolated way in experimental animals.13 Based on Ewald's work, who cannulated individual membranous canals in pigeons and observed the effects of endolymph motion on body, head, and eye movements.1416
The arrangement of the canals places fluid motion sensors at the ends of relatively long, slender, fluid-filled, donut-shaped tubes. Each tube lies more or less in one plane. The most effective stimulus to move the fluid in such a planar semicircular tube is angular acceleration in that plane, about an axis perpendicular to the plane and through the center of the “donut hole.” The three SCCs of the labyrinth are roughly orthogonal to each other, so that one labyrinth can sense any rotation in three-dimensional space. Canals in the two labyrinths are arranged in complementary, coplanar pairs.15 The two horizontal canals are roughly in one plane, which is nearly horizontal when the head is in an upright position. The left anterior canal is roughly coplanar with the right posterior canal in the LARP (left anterior-right posterior) plane, which lies ∼45° off the midsagittal plane with the anterior end toward the left and the posterior end toward the right. And the right anterior canal is roughly coplanar with the left posterior canal in the RALP (right anterior-left posterior) plane, again roughly 45° off the sagittal plane and orthogonal to the LARP and horizontal planes. These canal planes define the cardinal coordinate system for vestibular sensation. The power of this principle goes beyond the notion that the canal planes simply provide a coordinate system for vestibular sensation. Canal planes also provide the coordinate system for the final motor output of the VOR (and for the vestibulocolic neck reflex). The beauty of this canal-fixed (and thus head-fixed) coordinate system for eye movements is that it reduces the neural computation required for ocular motor output to exactly compensate for the head movement.
The VOR works like this: when the left horizontal canal is excited, secondary vestibular neurons that receive its afferents in the ipsilateral vestibular (medial and superior) nuclei connect to the ocular motor nuclei vestibular neurons controlling the medial and lateral rectus muscles, which also lie roughly in a horizontal plane. Secondary vestibular neurons carry excitatory signals to the ipsilateral third nucleus and contralateral sixth nucleus to excite the ipsilateral medial rectus and contralateral lateral rectus, respectively. These muscles pull the eyes toward the right as the head turns toward the left, accomplishing the goal of keeping the eyes stable in space. Other secondary vestibular neurons carry inhibitory signals to the contralateral third and ipsilateral sixth nuclei to simultaneously relax the antagonist muscles, the contralateral medial rectus and the ipsilateral lateral rectus, respectively. This reciprocal activity is typical of the extraocular muscles, which work in contraction-relaxation pairs.16 Just as the extraocular muscles work in reciprocal pairs, so too do the coplanar SCCs.
Thanks to the nonzero baseline firing rate of vestibular afferent neurons, both of the canals in a coplanar pair can encode rotational 17acceleration in that plane. Like the horizontal canals and the lateral and medial recti, the vertical SCCs are linked to the vertical pairs of eye muscles, a fact that helps explain the pulling directions and insertions of the superior and inferior oblique muscles.
The alignment of canal planes and extraocular muscle planes is not exact, and the excitation of a single canal pair does not solely produce activity in a dedicated pair of extraocular muscles. Other muscles must be activated to compensate for a head rotation even when it is purely in the plane of one SCC. However, this arrangement between SCCs and extraocular muscles is remarkably constant across vertebrate species, even allowing for the shift between lateral-eyed species (e.g. rabbits) and frontal-eyed ones (e.g. humans). Robinson17 has argued that there is an evolutionary advantage to keeping the extraocular muscles aligned with the SCCs. Such an arrangement minimizes the brainstem processing needed to activate the appropriate ensemble of eye muscles to compensate for head movement. Minimizing the number of synapses involved in the reflex preserves its remarkably short latency of ∼7 ms, which in turn minimizes retinal image slip during very rapid head movements.
Because of the primacy of the canals in determining how the eyes move under vestibular stimulation, it is helpful to think about vestibular eye movements in a canal-fixed frame of reference. When we examine a patient with benign paroxysmal positional vertigo (BPPV), it is possible to observe that following Ewald's first law the eyes will move in the plane of the stimulated canal no matter where gaze is directed.
An SCC crista is excited by rotation in its plane in one direction and is inhibited by rotation in its plane in the opposite direction. So, the head's turning toward the left in the horizontal canal plane produces endolymph rotation to the left relative to space. But that endolymph rotation is less than the head rotation. Thus, relative to the canal, there is endolymph rotation to the right, and the cupula is deflected toward the utricle. The pattern of afferent activation results from the polarization of the stereocilia of the hair cells on the cristae. In the horizontal canal, the taller ends of the bundles point toward the utricle. Flow of endolymph (relative to the head) toward the ampulla-ampullopetal flow (from Latin petere, to seek), therefore excites the horizontal canal afferents, and flow of endolymph away from the ampulla—ampullofugal flow (from Latin fugere, “to flee”)—inhibits these afferents. Thus, relative to the head, endolymph flow toward the ampulla occurs when the head is turning in the plane of the horizontal canal toward the same side.
The vertical canals, however, have the opposite pattern of hair cell polarization. The taller ends of the bundles point away from the utricle, so that flow away from the ampulla (ampullofugal) excites their afferents. 18For the left anterior canal, whose ampulla is at its anterior end, turning the head down and rolling it to the left in the plane of the left anterior canal results in relative endolymph flow that is ampullofugal?
For the left posterior canal, whose ampulla is at its posterior end, turning the head up and rolling it to the left in the plane of the left posterior canal moves its endolymph away from the ampulla and excites its afferents. The mirror-image rotations would pertain to the right vertical canals.
What is important to know is an SCC is excited by rotation in the plane of the canal bringing the head toward the ipsilateral side instead of ampullopetal and ampullofugal flows, so the right horizontal canal is excited by turning the head rightward in the horizontal plane; the right anterior canal is excited by pitching the head nose down while rolling the head toward the right in a plane 45° off of the midsagittal plane; the right posterior canal is excited by pitching the head nose up while rolling it toward the right in a plane 45° off the midsagittal plane. It should be obvious by now that an SCC is inhibited by rotation in the plane of the canal toward the opposite side. As described previously, the arrangement of canals is such that when head rotation excites one, it inhibits its coplanar mate. As noted earlier, endolymph flows relative to the membranous canal in a direction opposite to the head rotation. Thus, the left posterior canal is excited when endolymph flows upward and toward the right in the canal—that is, ampullofugal.
Perhaps because the VOR is critical to survival of any vertebrate that needs to see and move about its environment, evolution appears to have placed a high premium on maintaining parsimonious and rapid neural connections of head rotational sensors to eye muscles and made eyes working under vestibular system demands but it will respond at same way when there is a normal stimulus or a pathologic cause. It is the same thing on concern of systems that mediate postural reflexes and perception of spatial orientation. An important point is that the brainstem (and patient) will interpret any change in firing rate from vestibular afferents as indicating head rotation, tilt, or translation that would normally produce the same change in firing rate. Secondary vestibular neurons relay the same misinformation to other reflex control centers and higher areas of conscious sensation. This leads to autonomic and postural disturbances as well as the noxious sensation of vertigo, an illusion of self-motion. A pathologic asymmetry in input from coplanar canals causes the eyes to turn in an attempt to compensate for the “perceived” head rotation. However, given the mechanical constraints imposed by the extraocular muscles, the eyes cannot continue to rotate in the same direction that the canals command for very long. Instead, rapid, resetting movements occur, 19taking the eyes back toward their neutral positions in the orbits. The result is nystagmus, a rhythmic; slowly forward-quickly backward movements of the eyes. The quick resetting movements (similar to saccades) are quick phases of nystagmus, and the vestibular-driven slower movements are slow phases. Nystagmus direction is described according to the direction of the quick phases, because these are more dramatic and noticeable. However, an important point is that the slow phases are the components driven by the vestibular system. By focusing on the direction of slow phases, one reduces the number of mental inversions required to identify the pathologic canal causing an observed nystagmus. This principle holds almost universally true for brief, unpredictable changes in afferent firing, but not necessarily for persistent stable changes.
By using the example of PC-BPPV, it is describe how loose otoconia and endolymph flowed in an ampullofugal direction when the affected PC was oriented vertically in the Dix-Hallpike position: the direction of endolymph flow excites the PC afferents; the eye movements resulting from excitation of the PC will be in the plane of that PC; excitation of the PC afferents will be interpreted as an excitatory rotation of the head in the plane of the PC, and the nystagmus generated would be compensatory for the perceived rotation. For the left PC, excitatory rotation consists rolling the head toward the left while bringing the nose up. To keep the eyes stable in space, the VOR generates slow phases that move the eyes down and roll them clockwise (with respect to the patient's head).
It was described by Ewald14 that the movement of endolymph in the “on” direction for a canal produced greater nystagmus than an equal movement of endolymph in the “off” direction. It is known as Ewald's second law and it postulates an excitation-inhibition asymmetry. Excitation-inhibition asymmetries occur at multiple levels in the vestibular system. First, in the hair cells there is an asymmetry in the transduction process, which means that there is a larger receptor potential response for stereociliary deflection in the “on” direction than in the “off” direction. A second asymmetry is introduced by the vestibular nerve afferents. Recall that the afferents fire even when the head is at rest and that this firing is modulated by the hair cell responses to head acceleration after the endolymph and cupula integrate the signal to yield one representing head velocity. Vestibular afferents in mammals have baseline firing rates ranging from 50 to 100 spikes per second.18 Although these firing rates can be driven upward to 300–400 spikes per second, they can be driven no lower than zero. This inhibitory cutoff is the most obvious and severe form of excitation-inhibition asymmetry in the vestibular system. Goldberg et al.19 demonstrated that this asymmetry is more marked for irregular afferents.20
These peripheral asymmetries may be mostly eliminated in the central vestibular connections because of the reciprocal characteristics of signals from one side compared to another. In fact, such combination of nonlinear sensors acting reciprocally on a symmetrical premotor system can increase the linear range of the vestibular reflexes when both sides are functioning appropriately.20 However, nonlinearities in the VOR become pronounced when labyrinthine function is lost unilaterally.
Aw et al.21 demonstrated that VOR responses may be asymmetrical in humans after unilateral labyrinthectomy. The “head thrusts” test elicit rapid passive rotatory movements and occur like this: when the head is thrust in one of the SCC planes so as to excite the canal on the intact side, the VOR that results is nearly compensatory for the head movement, but when the head is thrust in one of the SCC planes so as to excite the canal on the lesioned side, the VOR that results is markedly diminished. Although head rotation produces an excitatory contribution from the ipsilateral horizontal canal and an inhibitory contribution from the contralateral one, these contributions are markedly asymmetrical under these conditions. The inhibitory contribution from the intact canal is insufficient to drive a compensatory VOR when the head is thrust toward the lesioned side, but the excitatory contribution from the intact canal that is obtained when the head is thrust toward the intact side is almost adequate to drive a fully compensatory VOR by itself. Such a marked asymmetry may not be evident for low-frequency, low-velocity rotations, which are not dynamic enough to cut off responses in the inhibited nerve.22 The head thrust test (HTT) has become one of the most important tools in the clinical evaluation of vestibular function. In its qualitative, “bedside” form, the examiner simply asks the subject to stare at the examiner's nose while the examiner turns the subject's head quickly along the excitatory direction for one canal. If the function of that canal is diminished, the VOR will fail to keep the eye on target, and the examiner will see the patient make a refixation saccade after the head movement is completed. When there is a loss of function well compensated, the refixation saccade may even occur while the head is completing its movement, and it may take some experience to spot the saccade while the head is still in motion. By contrast, when the head thrust is in the excitatory direction of an intact canal, the patient's gaze remains stable on the examiner's nose through-out the movement. The HTT can localize isolated hypofunction of individual SCCs.
It is not too common that natural head movements align solely with one canal plane; on the contrary, most rotations stimulate two or even all three of the pairs of canals. How much is each canal stimulated in such a rotation? The motion of the endolymph in each canal (relative to the canal) will determine the degree to which the hair cells in that canal 21are stimulated. The endolymph motion in each canal is proportional to the component of the head's rotational velocity acting in the plane of that canal. For example, a head rotation to the left with the head upright mostly stimulates the left horizontal canal. The component of head rotation operating on the horizontal canal is the projection onto the horizontal canal's sensitivity axis. However, note that the projections onto the sensitivity axes of the superior and posterior canals indicate excitatory stimulus acting on the ipsilateral superior canal and inhibitory stimulus acting on the ipsilateral posterior canal. The pattern of activity induced in the ampullary nerves therefore effectively decomposes a head rotation into mutually independent simultaneous components along the sensitivity axes. The actions of pairs of extraocular muscles are similarly combined. The extraocular muscles are arranged in pairs that approximately rotate the eyes around axes in the orbit that parallel the sensitivity axes of the canals. Simultaneous activation of extraocular muscle pairs in proportions similar to the proportions of canal activation will result in eye rotation around an axis parallel to that about which the head rotates, but in the opposite direction. This, of course, is the goal of the angular VOR. Given its ability to immediately sort incoming stimuli (head rotations) into spatially independent, minimally redundant channels of information, the labyrinth can be thought of as a “smart sensor” that not only measures stimuli but encodes them immediately in a maximally efficient way for downstream use in driving the angular VOR.
In this respect, it is analogous to the cochlea, which segregates sounds into separate bins of the frequency spectrum, and the retina, which spatially maps the world into a retinotopic space. Just as head rotations rarely stimulate only one pair of semicircular canals, labyrinthine disease rarely affects only one canal. The brain perceives the simultaneous activation of several canals as the head rotation that would produce the same component of activation along each canal's sensitivity axis. These components are linearly combined to produce an eye movement that would compensate for the perceived head movement. By observing the axis of the nystagmus, the examiner can deduce which combination of canals are being excited (or inhibited). This linear superposition of the canal signals for simultaneous stimulation of multiple canals was confirmed in an elegant series of experiments from Cohen and Suzuki16,23 by using cineoculography of eye movements and electromyographic recordings from extraocular muscles in cats while electrically stimulating ampullary nerves alone and in combinations. They observed that even highly nonphysiologic combinations of ampullary nerve stimuli caused eye movements and extraocular muscle activity that could be predicted as the vector summation of responses to each stimulus alone.22
Suzuki and Cohen24 showed what occurs when all of the canals on one side become excited from their baseline firing rates. The slow phase of the observed nystagmus has a horizontal component toward the contralateral side and a torsional component that moves the superior pole of the eye toward the contralateral side. The nystagmus beats to the ipsilateral side both horizontally and torsionally. There is no vertical component to this nystagmus. This irritative nystagmus can be seen when the labyrinth is irritated, for example, early in an attack of Ménière's disease, after stapedectomy procedures, and early in the course of viral labyrinthitis.
The same static imbalance in firing rates between sides occurs with unilateral labyrinthine hypofunction. Consider the case of left unilateral labyrinthectomy, in which case all three canals on that side are ablated. Unopposed activity of the right lateral canal contributes a leftward slow phase component. Unopposed activity of the right anterior canal contributes an upward and counterclockwise slow phase component. Finally, unopposed activity of the right posterior canal contributes a downward and counterclockwise slow phase component. These components combine, with the up and down components canceling each other, and with the net result being a leftward and counterclockwise slow phase (rightward- and clockwise-beating) nystagmus.
Nystagmus due to dysfunction of SCCs has a fixed axis and direction with respect to the head and it helps to distinguish nystagmus from a peripheral vestibular disorder from nystagmus due to a central disorder. In the case of the latter, the axis or direction of nystagmus may change depending on the direction of gaze.25 It is important to note that the magnitude of the nystagmus is not fixed depending on gaze. The reason for this is discussed in ahead.
The description of the VOR up to this point has depicted little role for brainstem and cerebellar signal processing, other than passing on the vestibular signals to the appropriate ocular motor nuclei. This “direct pathway” is the classical three-neuron reflex arc. However, the brainstem does more than serve as a conduit for the vestibular afferent signals. An “indirect pathway” through the brainstem circuits also must account for the poor performance of the vestibular end organs at low frequencies and the need for further integration of the incoming head velocity signal to generate fully compensatory eye movements. The brainstem accomplishes these tasks through processes called velocity storage and velocity-to-position integration. These two processes also lead to several important clinical phenomena, such as postrotatory nystagmus, post–head-shaking nystagmus, and Alexander's law. The last of these is another one of the cardinal signs that differentiates peripheral from central causes of nystagmus.23
Velocity Storage
For head rotations at frequencies below ∼0.1 Hz, the vestibular nerve afferent firing rate gives a poor representation of head velocity. In response to a constant velocity rotation, the cupula initially deflects but then returns back to its resting position, with a time constant of ∼13 seconds.26 Thus, nystagmus in response to a constant-velocity rotation would be expected to disappear after ∼30 seconds. In fact, the situation would be made somewhat worse because canal afferent neural responses also tend to decay for static- or low-frequency responses. This adaptation of afferent firing is a property of the neuron itself, and it is especially pronounced for irregular afferents.
The effect of adaptation is to make afferents respond more transiently to static- and low-frequency cupular displacements. Thus, some canal afferents end up carrying a transient signal in response to low-frequency and constant-velocity rotations. This signal more closely reflects the rate of change of head velocity—that is, acceleration—than velocity itself.
Despite these tendencies for the peripheral vestibular signals to decay prematurely, experimental observations in humans have shown that the time constant of the decay of the angular VOR for constant-velocity rotation is about 20 seconds, longer than would be expected based on the performance characteristics of the canals alone.27 Neural circuits in the brainstem seem to perseverate canal signals, stretching them out in time. The important physiologic consequence of this effect (historically called velocity storage, because it appears to “store” the head velocity information for some period of time) is that it allows the vestibular system to function better at low frequencies.
Robinson28 proposed that velocity storage could be accomplished by a feedback loop operating in a circuit including the vestibular nuclei. Lesion studies in monkeys suggest that velocity storage arises from neurons in medial vestibular nucleus and descending vestibular nucleus whose axons cross the midline.
Velocity storage is responsible for the prolonged nystagmus that occurs after sustained constant-velocity rotation in one direction. Rotation to one side generates a positive change in afferent firing on the ipsilateral side and a negative change on the contralateral side. Because of the excitation-inhibition asymmetry inherent in the SCC signals, the net result is not zero change in the afferent firing rate sensed by the brainstem, but rather a net excitation on the ipsilateral side. The velocity storage mechanism perseverates this net excitation beyond the time that the cupula deflection has returned to zero. The brainstem thus perceives that the head continues to rotate toward the same side, and it generates an angular VOR for that perceived rotation. The slow phases of nystagmus 24are directed toward the contralateral side, and the fast phases are directed toward the ipsilateral side. This nystagmus decays exponentially as the velocity storage mechanism discharges with the time constant of ∼20 seconds.
If the head is rotated side to side in the horizontal plane in normal subjects, the velocity storage mechanism is charged equally on both sides. There is no postrotatory nystagmus as the stored velocities decay at the same rate on either side. However, nystagmus does occur after head shaking in subjects with unilateral vestibular hypofunction. As the head is shaken from the lesioned side toward the intact side, net excitation is stored by the velocity storage mechanism. In fact, the net excitation is greater than in normal subjects because there is no inhibitory signal coming from the lesioned labyrinth. When the head is turned and rotated toward the lesioned side, there is no excitatory stimulus sent to the brainstem from that side, and only a small inhibitory stimulus from the intact labyrinth. After multiple cycles of back-and-forth rotation, a marked asymmetry develops in the velocity storage mechanism, one that signals illusory continued rotation toward the intact side. As a result, when the head stops rotating, the nystagmus is as would be expected for continued rotation toward the intact side: the slow phases go toward the lesioned side, and the fast phases toward the intact side. This pattern may even reverse after several seconds, presumably because neurons affected by velocity storage adapt to the prolonged change in firing from their baseline rates.
However, because the integrator is shared by other oculomotor systems, including the saccadic system, the ability to hold the eye in an eccentric position in the orbit is impaired when the integrator is leaky. As a result, the eyes tend to drift back to the center position in the orbits. This centripetal drift has an important effect on the observed nystagmus. When the eyes look toward the direction of the fast phase of nystagmus, the drift due to the “leakiness” of the integrator adds to the slow-phase velocity due to the vestibular imbalance, and as a result the nystagmus slow-phase velocity increases. However, when the eyes look toward the direction of the slow phase, the centripetal drift due to the leaky integrator subtracts from the slow-phase velocity due to the vestibular imbalance, and the nystagmus slow-phase decreases or may disappear. This observation has come to be known as Alexander's law.29 Although occasionally seen in central lesions, peripheral types of nystagmus generally will obey Alexander's law, making it an important neuro-otologic examination finding in distinguishing nystagmus of central origin from that of peripheral origin.25
The utricle senses linear accelerations that are tangential to some portion of its curved surface. Most of the utricle is approximately in the plane of the horizontal canal, although its anterior end curves upward from this plane. The baseline firing of utricular afferent fibers is therefore best modulated by linear accelerations in the horizontal plane—that is, fore and aft or side to side. Hair cells in the utricle are polarized such that stereociliary deflections toward the striola excite the hair cells, and deflections away from the striola inhibit them. The organ's pattern of responses is not too simple because the orientations of the stereociliary bundles vary over its surface. Linear accelerations in different directions probably activate unique ensembles of activity in the afferents of the utricle, with some areas being excited and others inhibited. These ensemble responses may encode the direction of head acceleration. Excitation or inhibition of all regions of the utricle does not occur under normal conditions of vestibular stimulation. Thus, predicting what the brain will perceive during pathologic conditions resulting in stimulation of the whole utricle is less straightforward than was the case for the SCCs, whose hair cells are all polarized in the same direction. Thus, the brain interprets a tonic increase in firing from the utricle on one side as a net acceleration of the otoconial mass toward the ipsilateral side and a decrease or loss in firing from the utricle on one side is interpreted as a net acceleration of the otoconial mass toward the contralateral or intact side. Such acceleration could be produced by an ipsilateral tilt or by a contralateral translational movement of the head. Just how the brain distinguishes utricular signals due to tilt from those due to translation remains one of the ongoing controversies in vestibular physiology. The equivalence of tilt and translation provides the brain a seemingly irresolvable ambiguity in the utricular afferent signals. Nevertheless, the brain is somehow able to correctly resolve the source of the ambiguous stimulus under normal conditions. Low-frequency or static linear accelerations acting on the otolith organs might be interpreted as gravitational accelerations resulting from tilt, whereas transient linear accelerations might be interpreted as linear translations.30,31 An alternative hypothesis is that the CNS integrates information from the SCCs with information from the otolith organs to distinguish tilts (which also transiently activate canals) from translations (which activate only the otolith organs).
An isolated loss of utricular nerve activity elicits a stereotypical set of static responses called the ocular tilt reaction: head tilt toward the lesioned side; disconjugate deviation of the eyes such that the pupil on the intact side is elevated and the pupil on the lesioned side is depressed 26(a so-called skew deviation), and a static conjugate counter-roll of the eyes rolling the superior pole of each eye away from the intact utricle. Each of these signs can be understood as the brain's compensatory response to a perceived head tilt toward the intact utricle. This perception arises from the excess of ipsilateral tilt information coming from the intact utricle.
The saccule is almost planar and lies in a parasagittal orientation. Hair cells of the saccule, polarized so that they are excited by otoconial mass displacements away from the striola, can sense accelerations fore or aft (along the naso-occipital axis) or up and down. Most afferents from the saccule have a preferred up or down direction.8a,b Thus, the sacculus has a unique role of sensing upward or downward. When the head is upright in the gravitational field, the acceleration due to gravity (9.8 m/s2) constantly pulls the saccular otoconial mass toward the earth. Afferents in the inferior half of the saccule, whose hair cells are excited by this downward acceleration, have lower firing rates and lower sensitivities to linear accelerations than do those afferents in the upper half of the utricle.8a,b The afferents in the upper half are excited by relative upward acceleration of the otoconial mass, such as might occur when the head drops suddenly, e.g. when one is falling. Thus, sudden excitation of hair cells across the saccular macula probably would be interpreted by the brain as a sudden loss of postural tone, as in falling. The appropriate compensatory reflex would be one that activates the trunk and limb extensor muscles and relaxes the flexors to restore postural tone. Accordingly, the saccular afferents project to the lateral portions of the vestibular nuclei, which give rise to the vestibulospinal tract, in contrast to the utricular afferents, which project more rostrally to areas involved in the VORs.
As emphasized throughout this chapter, the vestibular system is efficiently designed to give stereotypical motor reflex outputs that compensate for the movements of the head. Yet a stereotypical output appropriate for one context may be inappropriate for another. For example, redirection of gaze is accomplished by turning first the eyes, then the head, toward a new visual target. During the gaze shift, there is a period during which both the eyes and head must move in the same direction. The VOR must actually be turned off during this period; otherwise, the eyes would stay fixed on the original target. This cancellation of the VOR is measurable in secondary vestibular neurons as a decrease in VOR gain when gaze is being redirected. The mechanism by which the VOR can be canceled is not clear, but secondary vestibular neurons may receive “efference copies” of the commands going to the eye muscles. These oculomotor signals may, through inhibitory connections, decrease 27the responses of secondary vestibular neurons participating in the VOR reflex arc. Under other circumstances, the VOR gain may need to be increased. For example, when the eyes are verged to view a target near the nose, they must rotate through a larger angle than that fore head rotation, in order to stay on target. In fact, as head rotation brings one eye closer to the target and takes the other eye farther away from it, each eye will require a different VOR gain value. Viirre et al.32 showed that the VOR performs as needed under these demanding conditions to stabilize images on the retina, and it appears to do so within 10–20 ms of the onset of head movement—faster than could be explained by the use of any visual feedback information to correct the VOR. These investigators suggested that otolith interactions with canal signals could provide a means to constantly update an internal map of the visual target in space, allowing adjustments to the gain of the VOR for each eye.
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