Physiology of the Vestibular System
The human vestibular system participates in two important reflexes. These are the vestibulospinal reflex (VSR) and the vestibuloocular reflex (VOR). These reflexes function quickly and efficiently so as to correctly orient a person with relation to his environment at all times. This orientation leads to the person understanding the position of his body relative to itself as well as to the environment. This leads to stability without the person feeling dizzy. The vestibular system contributes to orientation during routine tasks such as standing upright or walking, as well as more complex motor tasks such as running or walking while turning the head. Independent movement of the eyes makes yet another demand on the nervous system for information processing
and control, namely,the need to maintain clear vision.
The input from the vestibular system differs from those of the other systems significantly in one aspect. The orientation information from the visual and proprioceptive receptors are generally relative to a reference frame that itself may vary with respect to an absolute frame of reference, such as that of gravity (4). These inputs must be converted to absolute orientation information to be useful in maintaining upright posture. The takeoff phase of a plane provides an example of the distinction between the sensory receptors. Because the visual system provides information relative to the external environment, it cannot provide accurate orientation information unless one can look out the window and first detect the orientation of the plane with respect to ground.
Similarly, the proprioceptive system provides information about the orientation of one body segment with respect to another body segment. For upright stability this information can be used to derive absolute orientation information only if the orientation of the support surface is known. If the support surface is moving or compliant, the proprioceptive cues are not likely to be an accurate representation of absolute orientation.
In contrast, the vestibular system during locomotion. provides absolute information regarding the orientation of the head with respect to gravity. Because the direction of gravity is not variable, the vestibular cues are not as easily affected as those from other Sensors. For this reason, as well as its frequency range. the vestibular system seems to operate as the final arbitrator in the hierarchical control of posture. That is if a discrepancy among the sensory inputs develops with regard to the orientation of posture, the VSR relies on vestibular signals to determine the appropriate strategy for preserving balance.
The visual equivalent of the vestibular system that contributes to generating compensatory eye movements is the optokinetic system. The optokinetic and vestibular reflexes are integrated to generate eye movement signals that can precisely counteract the head movements under a variety of conditions. The hallmark of optokinetic activation is the sensation of self-motion. The most compelling demonstration of this effect occurs when one car waiting at a traffic light starts to move. The driver of the adjacent vehicle, observing the motion in the peripheral vision, often perceives that it is his or her own car that actually is moving and reflexively pushes harder on the brake pedal, thus attempting to prevent the apparent movement.
In humans, two other visual subsystems contribute to the control of eye movements: the saccadic system and the smooth pursuit system. The saccadic system is responsible for generating fast eye movements that redirect the attention from one target to another, by quickly placing the image of the new target on the fovea. Because both the vestibular and optokinetic mechanisms cause the eyes to move away from center gaze, the saccadic system ensures that the eyes do not remain deviated to one side by quickly resetting the eyes toward the center gaze.
The smooth pursuit or tracking system is designed to keep the image of a moving target on the fovea. Smooth pursuit and optokinetic eye movements often are misidentified due to their close association. The smooth pursuit eye movements are voluntary, whereas the optokinetic eye movements are reflexive. The stimulus for the optokinetic system is the full visual field motion, whereas the smooth pursuit system is mainly activated by motion of small targets whose images fit within the fovea. Finally, the sensation of self-motion is the exclusive function of the optokinetic system activation. The interaction of the smooth pursuit with the vestibular system initially was thought to be inhibitory in nature; the smooth pursuit eye movements are used to suppress vestibular responses in conditions where they are deemed to be inappropriate for gaze stabilization for the purpose of providing clear vision during a wide range of conditions.
In addition to the visual system, the proprioceptive mechanisms contribute to gaze stabilization through the neck receptors and the cervicoocular reflex. Eye movements purely generated by the cervicoocular reflex can be seen in patients with bilateral loss of vestibular function as well as during movements of the torso relative to the stationary head.
It is only in recent years that the neural pathways that link the vestibular responses with the centers that control autonomic responses have begun to be identified There is speculation that autonomic responses such as nausea and vomiting act as a protective mechanism. The stimuli that trigger such responses usually are generated by movements that are intense and well beyond normal daily activities. It is also clear that the cardiovascular system faces significant challenges during standing or lying down due to changes in the height of the orthostatic column. Therefore, motion-induced changes in the autonomic responses seem to provide the necessary regulation during such activities.
The adaptive mechanisms appear to be activated when the vestibular responses are not within the anticipated behavior of the system. For example, most of our normal daily activities generate vestibular activities that are usually short in duration. When the responses do not subside quickly, as may be the case after a labyrinthine lesion or during an extended flight, a recalibration of the vestibular reflexes becomes necessary. The adaptive behavior of the vestibular receptors is not yet fully understood.
The plasticity of the neural pathways, although essential for optimal functioning of the VOR and VSR, poses a challenge in testing the vestibular system. Since the nature and timing of vestibular lesions can affect the outcome of function tests, the correct interpretation of the results depends on understanding the vestibular compensation process. Furthermore, the recent advances in the rehabilitation of patients with vestibular disorders are critically dependent on the design and implementation of physical therapy routines that activate the proper adaptive mechanisms.
The membranous labyrinth is suspended within the bony labyrinth through a group of connective tissues. The chemical composition of endolymphatic fluid resembles that of intracellular fluid with a higher ratio of potassium to sodium concentration. In an intact vestibular structure, there is no contact between the endolymphatic and perilymphatic fluids. The cochlear endolymph is most likely produced by the secretory cells within the stria vascularis. The dark cells are the most likely source of vestibular endolymph production. The absorption of endolymph is believed to occur in the endolymphatic sac.
The vestibular sensory cells are concentrated in different areas within the membranous labyrinth. Three of these areas arc located in the enlarged portion (ampulla) of each semicircular canal where the neuroepithelia, called the cristae ampullaris, reside. The macula of the utricle and saccule within the cavities of the vestibule also are packed with sensory cells. The arrange ment and spatial orientation of the sensory receptors within each area are unique, allowing for differential sensitivity to different types of head movement.
The membranous labyrinth receives its blood supply through the labyrinthine artery. The basilar artery is the supplier to the labyrinthine artery either directly, or more commonly through the anterior inferior cerebella branch. The vestibular portion of the labyrinthine artery has an anterior branch and a posterior branch, each supplying blood to various parts of the labyrinth. The posterior vestibular artery is a branch of the vestibulocochlear artery. The vestibular apparatus is susceptible to ischemia because the labyrinthine arteries lack collateral anastomotic connections with other major arterial branches . A short 15-second interruption of blood circulation can cause impairment of the sensory receptors. The impairment may become irreversible after a prolonged ischemia. Such events can damage one area of the labyrinth without affecting others, because the arterial branches take independent paths within the labyrinth
Despite the differences, type I and type II hair cells both have two important characteristics. First, the majority of them generate spontaneous neural firing at rest. The steady release of neurotransmitters across the junction of the hair cell and its afferent neurons appears to be the mechanism that provokes this tonic neural activity in the absence of any external stimulus. The magnitude of spontaneous firing varies among species. In mammals, the average spontaneous firing rate of each afferent nerve fiber is about 70 to 90 spikes per second (34). Because there are more than 20,000 fibers in each vestibular nerve, the tonic activity transmitted to the central pathways is on the order of an astonishing 1.5 million spikes per second!
The second common characteristic of the hair cells is their directional polarization. When the stereocilia bundle is bent toward the kinocilium, the firing rate of the afferent nerve fiber connected to that cell increases. Bending of the stereocilia away from the kinocilium causes a decrease in the firing rate. In general, the change in the firing rate of the afferent neuron is proportional to the displacement of the stereocilia. However, there is an inherent asymmetry between the excitatory and inhibitory responses. The firing rate of neurons can increase from the tonic level to approximately 400 spikes per second during the excitatory phase. However, the inhibitory responses are limited to cessation of the neural activity and therefore cannot exceed the spontaneous firing rate.
The most effective stimulus to hair cells is a force applied in a plane that passes that passes through the kinocilium and divides the stereo cilia bundle in half. Forces applied in the planes that are perpendicular to the described plane are not effective in activating the hair cell. The displacement of hair cells is proportional to the applied force and consequently to the acceleration of the motion, in the plane of hair cell activation. Most of our normal daily activities do not induce asymmetric behavior from the hair cells.
The hair cells within the labyrinthine neuroepithelia are surrounded by supporting cells. Supporting Cell liejust below the cuticle, where the kinocilium and stereocilia attach to the cell body, and extend to the base of the membrane. The support cells form a ring around the body of the hair cells. The tight binding between the two cell types separates the endolymph that surrounds the stereocilia and kinocilium from the perilymph that covers the base of the membrane.
Each semicircular canal forms a closed ring with an opening to a shared cavity in the utricular sac of the vestibule. The canal is filled with endolymphatic fluid. Near its junction with the utricular sac, the semicircular duct enlarges to form the ampulla. The crista ampullaris, the neuroepithelium packed with sensory hair cells, extends across the floor of the ampulla. A gelatinous mass called the cupula protrudes from the surface of the crista and completely seals the ampullar cavity. This fluid-tight plug partitions the semicircular canal duct into two chambers.
The cilia rise from the cell bodies on the crista and become embedded in the cupula. The nerve endings from the hair cells join to form a bundle that constitutes the primary afferent nerve fiber for each semicircular canal. An important characteristic of the hair cells in the crista ampullaris is their identical polarization direction. That is, in each crista, the hair cells are oriented with their kinocilia pointing in the same direction. Therefore, any movement of the cupula causes excitation or inhibition of all of the hair cells simultaneously. The orientation of hair cells in the lateral canal is the opposite of the orientation in the vertical canals. In the anterior and posterior canals the kinocilia are aligned toward the canal side of the ampulla. Thus, the deflection of the cupula away from the utricular sac (utriculofugal or ampullofugal) results in excitatory responses in the vertical canals. On the other hand, the kinocilia in the horizontal canals are polarised such that the deflection of the cupula toward the utricular sac (utriculopcdal or ampullopcdal) causes an increase in the neural firing rate.
The response characteristic of the semicircular canals to head movements is dependent on the fluid dynamics of the system. The cupula and the endolymph have identical densities (specific gravity of approximately 1.0). When the head is motionless, the cupula floats in the endolymph, keeping the hairs in their resting positions. The density of neural firing is equal to the sum of tonic inputs from individual nerve fibers. If the head is rotated in the plane of the canal, the canal walls follow the movement of the head; however, the viscosity of the endolymph causes a lag in the motion of the fluid, thus creating a relative motion of the endolymph with respect to the canal wall. Because the cupula completely blocks the flow of endolymph, the fluid motion generates a force across the cupula and bends it in the direction of endolymph flow. If the head rotation continues for an extended period of time at a constant velocity,the cupula eventually returns to its reposition as the fluid motion catches up with the motion of the canal wall. In humans, it takes about 15 to 20 seconds for the cupula to return to its resting position after a sudden change in the head velocity. If the head now is brought to a sudden stop, the relative motion of the endolymph to canal wall will be reversed and the cupula will be bent in the opposite direction. The pattern of neural firing in this case, as well as the sensation experienced by the subject, is the same as if the subject was rotated In the opposite direction of the initial head rotation, given again that the response of the hair cell is bidirectional.
It is clear from this discussion that the stimulus to the semicircular canals is the change in the angular velocity of the head, i.e., in essence, the acceleration of the head along a circular path. The semicircular canals are mostly unresponsive to motion in a straight line. However, the semicircular canals are by no means perfect angular accelerometers. The afferent neural firing pattern is a damped version of the head acceleration and does not exactly match it. The damping effect is due to the combination of inertia and friction posed by the endolymph-cupula dynamics (i.e., due to properties such as mass and viscosity). The neural firing rate nearly perfectly mirrors the head velocity for head movements that consist of brief acceleration and deceleration, with almost no period of constant velocity rotation. For these head movements, which are representative of natural head movements, the semicircular canals act as velocity meters. Another source of deviation from being an ideal accelerometer is the response asymmetry of individual canals for clockwise versus counterclockwise rotations, although asymmetries become apparent only for large-amplitude rotations and are not encountered in our normal daily activities. The asymmetry is due to the differences in the saturation level of excitatory and inhibitory responses of the hair cells. The synergetic pairing of the canals effectively neutralizes the effects of this asymmetry.
The linear motion of the head is not an effective stimulus for the semicircular canal system. Because the cupula and endolymph have the same density, linear accelerations, including gravity, generate little displacement of the cupula. Consequently, the neural activity of the canals produced by linear acceleration of the head is negligible.
The utricle and saccule are two cavities within the vestibule. They are filled with cndolymph and each con tains a sensory neuroepithelium, called the macula.
The macula of the utricle is an oval-shaped structure, with its average plane roughly parallel to that of the lateral semicircular canals. The macula of the saccule is also a curved structure, with its average plane roughly parallel to the vertical plane (more accurately, parallel to the sagittal plane bisecting the head). The macula is analogous to the crista in the semicircular canal. It is packed with hair cells and supporting structures necessary for transducing mechanical forces to neural firings. The cilia from the hair cells in each macula protrude into its own otolithic membrane. The otolithic membrane is analogous to the cupula of the canals. It consists of a gelatinous lower surface topped by crystal deposits called otoconia or otoliths. The otoconia are composed of calcium carbonate or calcite deposits of varying size (usually 5 to 7 um). Unlike the cupula, the specific gravity of the otolithic membrane is roughly three times higher than the specific gravity of the endolymph. Both maculae have a thin stripe through the middle of their otolithic membranes called the striola. The otoconia in this area are very small, and the thickness of the otolithic membrane is different compared to the adjacent tissue. In the utricle, the striola is thinner, whereas in the saccule. it is thicker than the surrounding membrane. The striola clearly divides the macula into regions in which the underlying hair cells have different patterns of polarization. Unlike the crista, the hair cells in the macula are not all polarized in the same direction. In the utricle, the hair cells are arranged with their kinocilia pointing toward the striola. In the saccule. the hair cells are aligned with the kinocilia pointing away from the striola. Because both maculae are nonplanar and both striolae are curved, the hair cell activation patterns are complex.The mechanism of stimulation for the otolith organs is any force that displaces the otolithic membrane with respect to the macula. Any arbitrary force applied to the head has two components, one that is parallel, and the other that is perpendicular, to the plane of the macula. The perpendicular component is a compressive force to the hair cells of that macula and therefore does not affect the firing rate of the corresponding afferent neurons. The parallel component, on the other hand, is a shear force that can displace the hair cells and generate neural activity. Because the maculae of the utricle and saccule lie roughly in perpendicular planes, any force component that is compressive to the hair cells in one macula will act as a shear force to the hair cells in the other macula. Therefore, the direction and the magnitude of any force can be decoded by its relative effect on the two maculae.
Because the applied force is proportional to the linear acceleration of the head the otolith organs are assumed to be linear accelerometers. This assumption is somewhat misleading however, because the induced neural activities are complex and not proportional to the linear acceleration of the head. It is more accurate to think of the otoliths as systems that are stimulated by linear acceleration of the head but with highly nonlinear response patterns that are yet to be fully characterized. On earth, the most prominent force of linear acceleration is gravity. Because of the specific configuration of the otoliths. they are intimately involved in detecting the direction of the gravitational vector. This is an important function that allows the vestibular receptors to provide absolute orientation information and distinguishes them from other sensory mechanisms. Clearly, the otolith receptors are capable of sensing dynamic changes of the head velocity, i.e.. acceleration. Because of their sensitivity to gravity, they also are capable of detecting static head lilts. This function is related to the fact that the relative distribution of the gravity vector on the two maculae changes depending on the direction and the magnitude of the head tilt.
Vestibular nerve fibers are bipolar neurons with their cell bodies in Scarpa's (vestibular) ganglion, their peripheral synapses on the hair cells, and their central synapses on the central vestibular structures. Scarpa's ganglion consists of two portions, a superior portion and an inferior portion. The latter comprises the nerve fibers from the crista of the posterior canal and the macula of the saccule. The nerve fibers from the remaining three vestibular receptors (cristae of the lateral and anterior canals and macula of the utricle) as well as a branch of the saccular nerve converge on the superior portion of the Scarpa's ganglion. The vestibular nerve maintains two branches as it leaves the superior and inferior ganglia.
The primary destination of the vestibular nerve fibers is the vestibular nuclei, although some fibers innervate the cerebellum directly . The vestibular nuclei are a group of neurons located mainly in the pons and extending into the medulla. Two sets of nuclei exist, one on the right side and the other on the left side. Each side consists of more than ten distinct groups of neurons . Four of them, the superior, medial, lateral, and descending nuclei, are considered the most prominent ones. Contrary to what is implied by the name, direct vestibular connections constitute only a fraction of the nerve fibers that innervate the vestibular nuclei. Other sources that supply afferent nerve fibers to the vestibular nuclei include the cerebellum, the reticular formation, the spinal cord, and the cervical area. There are also a considerable number of interconnecting fibers between the vestibular nuclei on the right and left sides. The efferent nerve fibers from the vestibular nuclei project to the same parts that supply afferent neurons to them.
As the vestibular neurons enter the brainstem. they take two separate pathways. The ascending pathway terminates either in the superior vestibular nucleus or in the cerebellum, while the descending branch terminates in one of the other three main vestibular nuclei. The vestibular nuclei are the main processors of the vestibular signal where the initial integration of the sensory inputs takes place. The role of the cerebellum is to monitor the vestibular responses and provide adaptive changes as necessitated by the changes in the environmental factors or the properties of the vestibular pathways.
The structures of the central vestibular pathways are an order of magnitude more complex than the peripheral. Significant gaps remain in our understanding of these pathways. Nonetheless, a brief discussion of the VOR and VSR is valuable for clinical assessment and management of vestibular disorders. The VOR pathways make two distinct connections between the vestibular nuclei and oculomotor neurons: a direct one using the nerve fibers in the medial longitudinal fascicules and an indirect one mediated through the reticular formation. The precise control of vestibuiar-driven eye movements requires coordinated activities of both pathways. Regardless of their pathway, project to the oculomotor nuclear complex: the third (oculomotor), the fourth (trochlear). and the sixth (abducens) nucleus, each nucleus is composed of a pair of cell groups, one on each side of the brain midline. Excitatory responses from one side usually are coupled with inhibitory responses from the opposite side to generate conjugate eye movements. The motor neurons from the oculomotor nuclei drive three pairs of extraocular muscles in each eye. The muscle pairs are arranged to move the eye in planes that roughly coincide with the planes of the semicircular canals. This arrangement simplifies the task of generating compensatory eye movements in response to head motion by enabling one pair of canals to drive only one pair of extraocular muscles. A functional description of the VOR pathways is provided in the next section The VSR pathways are far more complex than those of the VOR. This is not surprising considering that the task of postural control requires regulation of the activities of many more muscles and joints and integration of more complex sensory signals. The VSR is not a single reflex as is the VOR, but rather it is composed of a series of context-sensitive reflexes that are initiated on the basis of the available sensory inputs and the required motor task. The anterior horn cells of the spinal cord are the motor neurons that control the activities of the skeletal muscles. These motor neurons are connected to the vestibular nuclei via three primary pathways: the lateral vestibulospinal tract, the medial vestibulospinal tract, and the rcticulospinal tract. The first two trac project directly from the secondary vestibular neurons, whereas the third tract projects indirectly from the reticular formation that receives input from the vestibular nuclei. All three tracts are highly influenced by the cerebellum..
There are a number of advantages to the push-pull organization of the canal responses. First, it improves the resolution of the system by supplying the CNS with a signal that is twice as large as that produced by a single canal. Second, it desensitizes the system to changes in the afferent neural firing that are not produced by head motion. For example, changes in the body temperature or the chemical composition of the inner ear fluids alter the tonic activity of the vestibular neurons from a single canal. However, because these changes affect both labyrinths simultaneously, they are not falsely perceived as signals generated by head motion. Third, the push-pull arrangement of the canals provides a level of redundancy such that a failure of one labyrinth does not completely impair the vestibular function. Finally, this arrangement effectively neutralizes the inherent asymmetry between the excitatory and inhibitory responses of a single canal. High acceleration stimuli in one direction that saturate the inhibitory response of one canal will induce a similar saturation in the output of the paired canal for rotation in the opposite direction. Thus, the net input to the central vestibular pathways is the same regardless of the direction.
The process for generating compensatory eye movements in response to head rotation can be best illustrated by considering rotations in .the plane of the lateral semicircular canals. The arrangement of the hair cells in the lateral canals is such that the neural firing from the leading ear (the left ear. in this ease) increases, whereas (he firing rate from the opposite side decreases from its tonic level. For most normal dailv activities, the magnitude of the asymmetry between the responses from the two sides is proportional to the head velocity. This asymmetry is a signal to the central vestibular pathways to drive the eyes in the opposite direction of the motion with an amplitude that matches the head velocity.
To understand how neural activities from the peripheral vestibular system are converted to compensator eye movements, one must become familiar with the way oculomotor pathways generate eye movements in general. The neural command to the ipsilateral paramedian pontine reticular formation (PPRF) is a short-duration sudden surge in the firing rate (excitation pulse). The contralateral PPRF simultaneously receives a sudden decrease in the firing rate of the input neurons (inhibitory inverse pulse). Three pairs of muscles in each eye are used to move the eye in three different planes. The lateral rectus muscle and the medial rectus muscle move the eyes in the horizontal plane. For movements in any direction, one muscle contracts to pull the eye in the direction of movement (agonist muscle) while the paired muscle relaxes to allow movement in the opposite direction (antagonist muscle). For a rightward eye movement, the right lateral rectus and the right medial rectus muscles act as agonists and the right medial and left lateral rectus muscles act as antagonists. The excitatory pulse and inhibitory inverse pulse to the PPRF are transformed as they travel through the medial longitudinal fasciculus and oculomotor nuclei before supplying the muscles via the motor neurons. The agonist muscles receive a sudden increase in the neural firing rate followed by a drop to a new level that is slightly higher than the initial firing rate of the neurons (pulsestep), The pulse provides the muscle contraction to move the eyes quickly to the new position and the step allows the increased level of contraction required to keep the eyes in the new position. Similarly, the antagonist muscles receive an inverse pulse-step to provide the necessary muscle relaxation for initiating the eye movement and maintaining the new eye position. The responses of the oculomotor system to other stimuli can be inferred from the eye movements generated by the pulse command to the PPRF. Of particular interest are the stimuli generated by the secondary vestibular neurons from the vestibular nuclei. The afferent vestibular signal in response to an angular acceleration of the head is an increase in the firing rate of neurons from the leading ear and a decrease of firing rate from the opposite ear. For natural head movements, the excitatory neural tiring rate is approximately a triangular waveform resembling the head velocity. Unlike the pulse That, when applied to the PPRF, causes a quick change the eye position, the triangular waveform results in a slow drift of the eye from one position to another. The speed of the eye movement is proportional to the rate of the increase in neural firing and, consequently, to the velocity of the head. The signals from the vestibular nuclei cross the midbrain and connect to the ipsilateral PPRF. Thus, the response to a brief head action is a movement of the eyes in the opposite direction of head motion. Because the eye velocity matches head velocity, the eyes will remain virtually stationary in space.
When the head rotation is sustained, (he asymmetry in firing rate of the right-left vestibular neurons persists a much longer time. If there were no other intervention, the eyes would drift slowly in the opposite direction, :h their orbital limits, and remain in that position until neural asymmetry subsided. Because such a response ot desirable for maintaining a stationary image on the retina, a pulse is applied to the PPRF to move the eyes back toward the midline. The drift and the subsequent resetting of the eyes continue as long as the neural asymmetry persists. The source of the pulse is most likely the pulse generator in the saccadic system, which is responsible for moving the eyes quickly from one target to another. Intuitively, one might assume that eyes must reach the limit of the orbit before the pulse resets them to the center. In humans, however, the occurrence of the pulse appears to depend on the position and velocity of the eyes and can occur well in advance of the eyes reaching their limit. In other words, the pulse generator is triggered by an anticipatory process that keeps the eyes near the mid-line at all times. The specific to-and-fro pattern of eye movements generated by vestibular stimulation belongs to the class of eye movements known as nystagmus.
The studies of oculomotor responses mediated by the vertical semicircular vanals have been limited because of the complexity of the instruments needed to generate vertical stimuli as well as technical difficulties in recording vertical eye movements. Yet it is clear that the rotation of the head in the plane of the vertical semicircular canals does generate compensatory eye movements in that plane. The neural process, however, is complicated because the orientation of the planes of the semicircular canals and eye muscles is somewhat different. Therefore, the spatial information from the canals must be mapped on the coordinates of the eye muscles through a transformation. Such a transformation occurs as the semicircular canal output travels through the vestibular and oculomotor nuclei.
In addition to the acceleration of the head, two other conditions are necessary to observe vestibular nystagmus. First, the type of eye movements can be observed only in the absence of vision (eyes closed or in darkness). With vision present, other visual mechanisms. namely, the optokinetic and tracking systems, interact with the vestibular responses in generating compensatory eye movements. In the example in which the subject is suddenly stopped after a prolonged rotation, vestibular nystagmus can be observed in darkness. However. when vision is permitted, vestibular nystagmus is quickly suppressed. This is functionally reasonable because, in the absence of head motion, such compensatory eye movements are not required. The second condition for the formation of vestibular nystagmus is the mental alertness of the subject. Alertness appears to be necessary only for generating the fast phase of the nystagmus. It has been demonstrated that vestibular stimulation in comatose individuals does produce the slow drift of the eyes . However, once the eyes reach the periphery of the orbit, they remain deviated to one side.
An important property of the VOR pathways is revealed by examining eye movement responses during a prolonged constant-velocity rotation. The canal response consists of a sudden change in the firing rate of the peripheral neurons, which returns to its baseline exponentially as the cupula returns to its resting position. The intensity of the resulting vestibular nystagmus (slow-phase velocity) also undergoes a similar pattern, rising immediately after the initiation of motion and dissipating exponentially over time. However, there is a significant difference between the time course of the two events. Whereas the canal responses disappear after 15 to 20 seconds, the nystagmus persists almost three times longer. The prolongation of the nystagmus is due to a neural integrator aptly named the velocity storage mechanism. The integrator acts as a storage tank in which an outflow valve can control the flow of neural activity so that it is not as rapid as the inflow. Consequently, there is a buildup of the neural activity that continues even after the input signal has ceased. The overall effect of the velocity storage mechanism is to extend the frequency response of the VOR pathways to lower frequencies. The gain (ratio of slow-phase eye velocity to head velocity) and phase (temporal difference of slow-phase eye velocity to head velocity) are shown for different frequencies of sinusoidal head movements. For ideal compensatory eye movements, the slow-phase eye velocity will be exactly the same amplitude as the head velocity but in the opposite direction. The frequency responses show the deviation of the resulting eye movements from ideal ones for different frequencies. When the gain is equal to one and the phase is equal to zero, the eye movements are completely compensatory. Without the velocity storage mechanism, the ideal responses are limited to the frequency range from 0.3 to 10 Hz. For frequencies lower than 0.3 Hz, the slow-phase eye velocity is less than the head velocity (gain less than one), and there is a time difference between the two (phase greater than zero). With the addition of the velocity storage mechanism, the effective range of the canal-ocular responses is extended to 0.1 to 10 Hz.
The underlying mechanism for the movement of the endolymph during caloric irrigations is the temperature-induced change in the density of the endolymph. For example, a warm stimulus causes the fluid closest to the auditory canal to become lighter than the rest of the endolymph and rise due to the effect of gravity. This causes an excitatory response of the afferent neurons from the irrigated ear. The asymmetry between the neural firing rates from the two labyrinths is identical to that produced by the horizontal angular acceleration of the head toward the irrigated ear. Similarly, the resulting vestibular nystagmus has the same characteristics as those described earlier. A cold irrigation of the ear results in the flow of the endolymph in the opposite direction and decreases the neural firing rate of the irrigated ear. An acronym, COWS (cold opposite, warm same), is used to quickly identify the direction of the nystagmus generated by different irrigations. For example, cool irrigation of the left ear causes right-beating nystagmus exactly the same way as if the patient was being accelerated toward the right ear. It is clear from this discussion that gravity is essential to explain the theory for generation of caloric responses. However, experiments in the space shuttle in the early 1980s cast doubt on the validity of this assumption when caloric responses were apparently produced in the absence of gravity. Yet compelling evidence remains to support the explanation. Warm irrigation of the external auditory canal in this head position generates ampullofugal flow and decreases the neural firing rate from the irrigated side. The change in the direction of the nystagmus when the subject moves from supine to prone or from prone to supine can be interpreted only by considering die reversing the gravity vector. Today, the general is that gravity is primarily responsible for caloric responses, although small changes m d rate of the neurons can be attributed to the direct the temperature on the afferent nerve fibres.
Caloric responses are mediated primarily by the lateral semicircular canals. Theoretically, it also is possible to generate caloric responses from vertical canals if they are placed in the plane of gravity. However, the anatomic organization of the labyrinths is such that the vertical semicircular canals are distant from the external auditory canal. As a result, it is not possible to create the temperature gradient necessary to generate adequate vestibular stimulation for the vertical canals.
As is the case for the semicircular canals, stimulation of the otoliths also is expected to produce compensatory eye movements. Electrical stimulation of the utricular and saccular nerve fibers, as well as direct stimulation of macular regions, produce steady eye deviations. The direction of the eye deviations depends on the polarization hair cells in each region. Nystagmus eye movements have been reported, but it is not clear whether nystagmus responses were the result of inadvertent stimulation of semicircular canal nerve fibers .
When otolith stimulation is generated by head tilts, the resulting eye movements can be either torsional (rotation of the eyes in the orbit about the visual axis) or rotational (similar to horizontal eye movements but may include a vertical component). The type of response is different among species and depends on the orientation of eyes and the direction of tilt. In humans, lateral head tilts generate torsional eye movements known as ocular counter-rolling. Although these eye movements are compensatory, they are not efficient in counteracting the effect of head tilts. The amplitude of eye torsion even for large tilts is only around 10% of the amplitude of the head tilt. Head lilts in the pitch plane generate vertical movements of the eves. However, the effect of the vertical semicircular canals in generating such eye movements during the acceleration phase of the tilt should not be overlooked.
The effect of linear head acceleration in generating compensatory eye movements is more controversial. If the otoliths are viewed as sensors that respond to the combination of all forces applied to the head, then compensatory eye movements for linear acceleration in the lateral plane (along the interaural axis) will be ocular counterrolling similar to those generated by lateral head tilts. Instead, experiments using such an acceleration have produced horizontal nystagmus. Similarly, linear accelerations in the pitch plane ( along the occipitonasal axis) have failed to produce vertical eye movement as expected. These observations indicate that the otolithocular pathways do not respond the same way to other linear accelerations as they vestibular receptors is to complement the visual system. This can be best accomplished if gravity is treated differently than other linear accelerations that induce motion.
Overall, otolith-induced eye movements are not studied as extensively as those produced by the semicircular canals. Significant gaps remain in our understanding of the organization and the exact function of the otolith-ocular pathways.
As noted before, normal vestibular responses usually are short in duration, often lasting only a few seconds. When the asymmetry from right-left afferent nerve fibers persists for longer than the anticipated time, the sensitivity of the VOR, and consequently the intensity of the nystagmus is reduced. This adjustment can take place in a relatively short period of time. For example, if caloric stimulation is applied for an extended period of time, the adaptive changes can begin within a few minutes. Similarly, repeated stimulation of the vestibular system can activate the adaptive mechanisms. For example, the intensity of induced nystagmus declines after repeated exposure to rotation. A more drastic example of adaptation occurs during space flights. Removal of the gravitational vector causes a change in the firing pattern of the otolith neurons. Whereas a change in the gain of the VOR may be helpful in the short term to alleviate motion sickness symptoms, a more intricate change in the organization of the otolith pathways is needed to deal with the long-term consequences of space flight on the vestibular system. Once the astronauts return to earth, a similar reorganization must take place to adapt to gravity.
The sudden unilateral loss of labyrinthine function produces vestibular nystagmus that is predominantly horizontal but sometimes also has a torsional component. The horizontal component of the nystagmus is caused by the loss of tonic activity from the afferent neurons of the lateral canal on the damaged side. The slow phase of this nystagmus will be directed toward the damaged side because the CNS perceives the head rotation being toward the intact ear. It should be noted, however, that the direction of nystagmus can change because of vestibular compensation and is not always a reliable indicator of the side of lesion (see followmu). Pathologic vestibular nystagmus does not have a vertical component. Vertical eye movements that are generated by the vertical semicircular canals from one ear in the opposite direction. The net result is the cancellation vertical component because the anterior and posterior canals from the intact side have no functioning match in the damaged side. These canals produce torsion eye movement that are in the same direction, thus explaining the torsional component of the nystagmus .
Acute unilateral vestibular loss also causes other postural abnormalities, including head tilt toward the side of lesion disequilibrium. Many of these effects are temporary and recover quickly after compensation. One manifestation of unilateral vestibular loss, which seems to persist permanently, is a static torsion of the eyes toward the side of lesion. This ocular tilt reaction is likely caused by the unilateral loss of otolithic function.
The asymmetry in the neural firing rates immediately after a sudden unilateral vestibular loss is reduced by "clamping" the neural activity of the intact labyrinth . This step can begin within days, if not hours, after the initial damage to the labyrinth. The increase in the asymmetry of neural activities reduces the intensity of the symptoms. The effect is similar to that of the antivertiginous medications that suppress the vestibular activity at the brainstem level. Within 1 week after the onset of the lesion, neural activity appears in the vestibular nuclei at the site innervated by the afferent nerve fibers from the damaged side. This neural activity originates not from the labyrinth, but from other sources within the CNS. At the same time, the activity from the tact side begins to increase as the clamping of the vestibular input is eased. After a few weeks, the static condensation is completed when the tonic neural firing from intact side returns to its prelesion level and the neural activity is restored at the vestibular nuclei of the damaged. The static compensation process occurs regardless of whether the unilateral vestibular loss is sudden or gradual. In case of a gradual loss, the entire compensation process takes place repeatedly in small increments. As a result, a patient with such a loss may not experience the kind of severe symptoms associated with a sudden unilateral lesion.
After a unilateral vestibular loss, the inherent asymmetry between the excitatory and inhibitory neural firings from one semicircular canal is no longer offset by the responses from the paired canal. Therefore, it is expected that the responses for clockwise and counterclockwise rotations will be asymmetric after a unilateral lesion. In practice, this type of asymmetry is seen only in the early stage of static compensation during the period when the responses from the intact ear are suppressed. In this stage, rotation away from the side of lesion will quickly saturate the response as the neural firing rate is reduced to zero. The rotation toward the intact side will be unaffected as the excitatory responses can increase significantly more. After the completion of static compensation, the response asymmetries can be seen only for high-acceleration stimuli.
The process of static compensation is most effective when the lesion is stable. Fluctuations in the status of the labyrinth disrupt the compensation process and cause symptoms that usually are more troublesome to the patient than those caused by a stable lesion, even when the lesion is permanent. If function is restored to the damaged labyrinth during the compensation steps for which the neural activity of the intact side is suppressed, the asymmetry in the neural activity of right-left labyrinths will be reversed. This reversal leads to eye movements known as recovery nystagmus. The slow phase of the recovery nystagmus is in the opposite direction of the slow phase of the nystagmus seen immediately after an acute vestibular lesion. Otherwise, the two types of nystagmus have identical characteristics and cannot be differentiated. Therefore, one cannot rely solely on the direction of the nystagmus as an indicator of side of lesion.
It is clear that head rotation will generate the neural asymmetry necessary for detecting the direction of rotation. However, the magnitude of the asymmetry is half of that generated by two functioning labyrinths for the same head acceleration. During the dynamic phase of compensation, the vestibular pathways are recalibrated such that the new pattern of the head velocity to neural firing rates is transformed into compensatory eye movements with appropriate intensities. Intuitively, the gain of the VOR pathways must be doubled to generate the same amplitude of eye movements as those generated before the lesion. However, because the VOR is a dynamic system, a change in the gain of the pathway could affect other characteristics, including its frequency response. Recall the analogy used for the velocity storage mechanism. One way to increase the sensitivity is to increase the gain of the integrator in the VOR pathway. This is analogous to increasing the outflow of the velocity storage mechanism. Although this action increases the sensitivity, it also diminishes the storage capacity of the integrator. Consequently, the low-frequency performance of the system will be degraded..
Degradation of low-frequency VOR performance is associated with unilateral loss of vestibular function. Rotational tests in patients with such lesions show that the ratio of the slow-phase eye velocity to head velocity decreases and the phase difference between them increases for low frequencies. However, the process of dynamic compensation is more complex than simply increasing the gain of the VOR. Most likely, a remapping of the vestibular signals is necessary to ensure precise integration of the information from all sensory mechanisms.
Bilateral vestibular lesions can be complete or partial. The loss of function for partial lesions is confined to low-frequency head movements, whereas the high-frequency responses are preserved until the loss is complete. In the case of a complete vestibular loss, there is no vestibular-mediated' mechanism to restore function. Instead, the central compensation mechanisms utilize other sensorimotor inputs to substitute for the labyrinthine function. The visual and neck receptors are the most appropriate alternatives for both postural and visual stabilization. The compensation methods for bilateral lesions are not nearly as effective as the methods described for unilateral lesions. Patients with complete and permanent bilateral lesions are not as likely to regain their prelesion functional status as well as patients with a unilateral loss.
Vestibulospinal Reflex
The vestibular receptors participate in maintaining upright postural stability and generating purposeful movements by providing the central nervous system (CNS) with sensory information about the movements and orientation of the head. The VSR, which generates compensatory body movements, includes the peripheral vestibular end organs, central vestibular pathways, and motor centers such as the spinal cord. In addition to vestibular input, the VSR receives information from other sensory systems which include the visual and proprioceptive systems. There is considerable overlap among the sensory inputs therefore the frequency range for optimal operation of each sensor is completely distinct. For example, the visual system operates best for slow, low-frequency movements, whereas the proprioceptive system is best suited for fast, high-frequency activities. The frequency range of the vestibular receptors, approximately 0.1 to 3 Hz, falls somewhere between the operational frequencies of visual and proprioceptive inputs and corresponds well with the natural frequency of head movements.The input from the vestibular system differs from those of the other systems significantly in one aspect. The orientation information from the visual and proprioceptive receptors are generally relative to a reference frame that itself may vary with respect to an absolute frame of reference, such as that of gravity (4). These inputs must be converted to absolute orientation information to be useful in maintaining upright posture. The takeoff phase of a plane provides an example of the distinction between the sensory receptors. Because the visual system provides information relative to the external environment, it cannot provide accurate orientation information unless one can look out the window and first detect the orientation of the plane with respect to ground.
Similarly, the proprioceptive system provides information about the orientation of one body segment with respect to another body segment. For upright stability this information can be used to derive absolute orientation information only if the orientation of the support surface is known. If the support surface is moving or compliant, the proprioceptive cues are not likely to be an accurate representation of absolute orientation.
In contrast, the vestibular system during locomotion. provides absolute information regarding the orientation of the head with respect to gravity. Because the direction of gravity is not variable, the vestibular cues are not as easily affected as those from other Sensors. For this reason, as well as its frequency range. the vestibular system seems to operate as the final arbitrator in the hierarchical control of posture. That is if a discrepancy among the sensory inputs develops with regard to the orientation of posture, the VSR relies on vestibular signals to determine the appropriate strategy for preserving balance.
Vestibuloocular Reflex
The other important function in which the vestibular system participates is the task of providing clear vision during movements of the head. This task is accomplished through the VOR, which maintains a steady retinal image by generating compensatory eye movements in response to head motion. In addition to the vestibular pathways, other sensorimotor mechanisms participate in the stabilization of gaze. These mechanisms participate in extending the operational frequency range of the VOR and provide the necessary redundancy to make the overall system more fault tolerant.The visual equivalent of the vestibular system that contributes to generating compensatory eye movements is the optokinetic system. The optokinetic and vestibular reflexes are integrated to generate eye movement signals that can precisely counteract the head movements under a variety of conditions. The hallmark of optokinetic activation is the sensation of self-motion. The most compelling demonstration of this effect occurs when one car waiting at a traffic light starts to move. The driver of the adjacent vehicle, observing the motion in the peripheral vision, often perceives that it is his or her own car that actually is moving and reflexively pushes harder on the brake pedal, thus attempting to prevent the apparent movement.
In humans, two other visual subsystems contribute to the control of eye movements: the saccadic system and the smooth pursuit system. The saccadic system is responsible for generating fast eye movements that redirect the attention from one target to another, by quickly placing the image of the new target on the fovea. Because both the vestibular and optokinetic mechanisms cause the eyes to move away from center gaze, the saccadic system ensures that the eyes do not remain deviated to one side by quickly resetting the eyes toward the center gaze.
The smooth pursuit or tracking system is designed to keep the image of a moving target on the fovea. Smooth pursuit and optokinetic eye movements often are misidentified due to their close association. The smooth pursuit eye movements are voluntary, whereas the optokinetic eye movements are reflexive. The stimulus for the optokinetic system is the full visual field motion, whereas the smooth pursuit system is mainly activated by motion of small targets whose images fit within the fovea. Finally, the sensation of self-motion is the exclusive function of the optokinetic system activation. The interaction of the smooth pursuit with the vestibular system initially was thought to be inhibitory in nature; the smooth pursuit eye movements are used to suppress vestibular responses in conditions where they are deemed to be inappropriate for gaze stabilization for the purpose of providing clear vision during a wide range of conditions.
In addition to the visual system, the proprioceptive mechanisms contribute to gaze stabilization through the neck receptors and the cervicoocular reflex. Eye movements purely generated by the cervicoocular reflex can be seen in patients with bilateral loss of vestibular function as well as during movements of the torso relative to the stationary head.
The Autonomic System and the Vestibular System
A number of animal studies have established the direct role of the vestibular system in generating motion-induced autonomic symptoms. In these studies, animals produced emesis responses after prolonged or excessive vestibular stimulation. When the vestibular apparatus was destroyed in some animals by labyrinthectomy or differentiation of the vestibular nerve, those animals no longer exhibited the emesis response after vestibular stimulation. On the other hand, the control animals with the intact vestibular system continued to suffer from the autonomic symptoms.It is only in recent years that the neural pathways that link the vestibular responses with the centers that control autonomic responses have begun to be identified There is speculation that autonomic responses such as nausea and vomiting act as a protective mechanism. The stimuli that trigger such responses usually are generated by movements that are intense and well beyond normal daily activities. It is also clear that the cardiovascular system faces significant challenges during standing or lying down due to changes in the height of the orthostatic column. Therefore, motion-induced changes in the autonomic responses seem to provide the necessary regulation during such activities.
The Vestibular Response and Adaptation
The vestibular pathways adapt rapidly. Adaptation is essential to overcome the effects of changes due to disease and trauma as well as environmental and developmental changes, such as aging. When the changes are due to dysfunction of the vestibular system, the adaptive process usually is referred to as vestibular compensation. However, regardless of whether the changes are due to natural or disease processes, the adaptive strategies appear to be similar. Such strategies may include readjusting the properties of the vestibular response (magnitude, timing) or substituting alternative sensory mechanisms.The adaptive mechanisms appear to be activated when the vestibular responses are not within the anticipated behavior of the system. For example, most of our normal daily activities generate vestibular activities that are usually short in duration. When the responses do not subside quickly, as may be the case after a labyrinthine lesion or during an extended flight, a recalibration of the vestibular reflexes becomes necessary. The adaptive behavior of the vestibular receptors is not yet fully understood.
Evaluation of the Vestibular Function and its Clinical Implications
There is no direct access to the human vestibular end organ. We rely on secondary responses, such as eye or postural movements, to evaluate the vestibular system. Since many other sensory mechanisms participate in the control of eye and postural movements, it is unsurprising that vestibular tests frequently yields nonspecific and nonlocalizing findings.The plasticity of the neural pathways, although essential for optimal functioning of the VOR and VSR, poses a challenge in testing the vestibular system. Since the nature and timing of vestibular lesions can affect the outcome of function tests, the correct interpretation of the results depends on understanding the vestibular compensation process. Furthermore, the recent advances in the rehabilitation of patients with vestibular disorders are critically dependent on the design and implementation of physical therapy routines that activate the proper adaptive mechanisms.
Anatomy of Vestibular System
The vestibular receptors are embedded within the membranous labyrinth. The membranous labyrinth is enclosed within the bony labyrinth, a series of hollow channels in the petrous portion of the temporal bone the auditory sensory receptors. The space for the bony labyrinth is divided into three distinct parts: a cochlear part, a vestibular part, and a central chamber called the vestibule. The vestibular portion consists of three semicircular canals with their openings converging at the vestibule. The bony labyrinth is filled with perilymphatic fluid, which is similar to that of the extra cellular fluid with a higher ratio of sodium to potassium concentration. The electrolyte composition of perilymph is similar to that of the cerebrospinal fluid.The membranous labyrinth is suspended within the bony labyrinth through a group of connective tissues. The chemical composition of endolymphatic fluid resembles that of intracellular fluid with a higher ratio of potassium to sodium concentration. In an intact vestibular structure, there is no contact between the endolymphatic and perilymphatic fluids. The cochlear endolymph is most likely produced by the secretory cells within the stria vascularis. The dark cells are the most likely source of vestibular endolymph production. The absorption of endolymph is believed to occur in the endolymphatic sac.
The vestibular sensory cells are concentrated in different areas within the membranous labyrinth. Three of these areas arc located in the enlarged portion (ampulla) of each semicircular canal where the neuroepithelia, called the cristae ampullaris, reside. The macula of the utricle and saccule within the cavities of the vestibule also are packed with sensory cells. The arrange ment and spatial orientation of the sensory receptors within each area are unique, allowing for differential sensitivity to different types of head movement.
The membranous labyrinth receives its blood supply through the labyrinthine artery. The basilar artery is the supplier to the labyrinthine artery either directly, or more commonly through the anterior inferior cerebella branch. The vestibular portion of the labyrinthine artery has an anterior branch and a posterior branch, each supplying blood to various parts of the labyrinth. The posterior vestibular artery is a branch of the vestibulocochlear artery. The vestibular apparatus is susceptible to ischemia because the labyrinthine arteries lack collateral anastomotic connections with other major arterial branches . A short 15-second interruption of blood circulation can cause impairment of the sensory receptors. The impairment may become irreversible after a prolonged ischemia. Such events can damage one area of the labyrinth without affecting others, because the arterial branches take independent paths within the labyrinth
Hair Cell Structure
The vestibular sensory receptors are members of a group of specialized cells that transduce mechanical energy to neural activities. These cells, referred to as hair cell due to their unique structure, are similar to those found in the organ of Corti. The energy of the stimulus is from hydro mechanical and generated in association with the forces that are produced cither by head movements or n gravity. Microscopic displacement of the hair cells subsequent to the applied force causes the chemical reaction that releases neurotransmitter substance and changes the neural firing rate of the primary vestibular neurons. Three major parts can be identified: the cilia, the cell body, and the nerve endings. The cilia, or hairs, are the distinctive feature of these sensory cells. In the vestibular apparatus, the cilia of the sensory cells consist of approximately 70 short hairs called stereocilia and a single, thicker, longer hair called a kinocilium The stereocilia do not surround the kinocilium, nor do they line up in a plane. Instead, they form a bundle atop the cell body with the kinocilium on one side. This is a relatively rigid bundle as the applied force is easily transmitted from one hair to the other. The length of the stereocilia for each hair cell increases as they get closer to the kinocilium. However, the relative length of stereocilia is variable for hair cells in different receptor organs and even for hair cells in different locations within the same organ. Two types of vestibular hair cells have been identified in mammals. The main morphologic differences between the two types are in the shape of the cell body and the connection of the nerve endings to the cell body. Type I hair cells have a cell body that is narrower at the apex and wider at the base, much like a flask. These cells are distinguished by the presence of a large afferent nerve ending termed the chalice or calyx. In type I cells, the calyx almost completely surrounds the cell body. The efferent nerve ending is attached to the calyx and does not directly contact the body of a type I cell. Type II hair cells have a cylindrical cell body with multiple afferent nerve connections. The efferent nerve terminal in type II cells lies directly on the cell body.Despite the differences, type I and type II hair cells both have two important characteristics. First, the majority of them generate spontaneous neural firing at rest. The steady release of neurotransmitters across the junction of the hair cell and its afferent neurons appears to be the mechanism that provokes this tonic neural activity in the absence of any external stimulus. The magnitude of spontaneous firing varies among species. In mammals, the average spontaneous firing rate of each afferent nerve fiber is about 70 to 90 spikes per second (34). Because there are more than 20,000 fibers in each vestibular nerve, the tonic activity transmitted to the central pathways is on the order of an astonishing 1.5 million spikes per second!
The second common characteristic of the hair cells is their directional polarization. When the stereocilia bundle is bent toward the kinocilium, the firing rate of the afferent nerve fiber connected to that cell increases. Bending of the stereocilia away from the kinocilium causes a decrease in the firing rate. In general, the change in the firing rate of the afferent neuron is proportional to the displacement of the stereocilia. However, there is an inherent asymmetry between the excitatory and inhibitory responses. The firing rate of neurons can increase from the tonic level to approximately 400 spikes per second during the excitatory phase. However, the inhibitory responses are limited to cessation of the neural activity and therefore cannot exceed the spontaneous firing rate.
The most effective stimulus to hair cells is a force applied in a plane that passes that passes through the kinocilium and divides the stereo cilia bundle in half. Forces applied in the planes that are perpendicular to the described plane are not effective in activating the hair cell. The displacement of hair cells is proportional to the applied force and consequently to the acceleration of the motion, in the plane of hair cell activation. Most of our normal daily activities do not induce asymmetric behavior from the hair cells.
The hair cells within the labyrinthine neuroepithelia are surrounded by supporting cells. Supporting Cell liejust below the cuticle, where the kinocilium and stereocilia attach to the cell body, and extend to the base of the membrane. The support cells form a ring around the body of the hair cells. The tight binding between the two cell types separates the endolymph that surrounds the stereocilia and kinocilium from the perilymph that covers the base of the membrane.
The Structure of Semicircular Canals and its Functional Significance
There are three semicircular canals within each labyrinth-— lateral (or horizontal), anterior (or superior1), and posterior. These canals are organized in three nearly orthogonal (i.e., mutually perpendicular) planes. The lateral canal resides in a plane that makes a 30-degree upward angle with the horizontal plane when the head is in a natural upright position. The other two canals are roughly vertical, each oriented at an approximately 45-degree angle with respect to the sagittal plane that bisects the head. Each semicircular canal in the right ear is synergistically paired with a canal in the left ear such that they reside in approximately parallel planes. The three pairs consist of two lateral canals, right anterior and left posterior canals, and right posterior and left anterior canals. Because the semicircular canals are not perfectly perpendicular and because the canal pairs are not exactly parallel, most natural head movements stimulate all of the semicircular canals simultaneously.Each semicircular canal forms a closed ring with an opening to a shared cavity in the utricular sac of the vestibule. The canal is filled with endolymphatic fluid. Near its junction with the utricular sac, the semicircular duct enlarges to form the ampulla. The crista ampullaris, the neuroepithelium packed with sensory hair cells, extends across the floor of the ampulla. A gelatinous mass called the cupula protrudes from the surface of the crista and completely seals the ampullar cavity. This fluid-tight plug partitions the semicircular canal duct into two chambers.
The cilia rise from the cell bodies on the crista and become embedded in the cupula. The nerve endings from the hair cells join to form a bundle that constitutes the primary afferent nerve fiber for each semicircular canal. An important characteristic of the hair cells in the crista ampullaris is their identical polarization direction. That is, in each crista, the hair cells are oriented with their kinocilia pointing in the same direction. Therefore, any movement of the cupula causes excitation or inhibition of all of the hair cells simultaneously. The orientation of hair cells in the lateral canal is the opposite of the orientation in the vertical canals. In the anterior and posterior canals the kinocilia are aligned toward the canal side of the ampulla. Thus, the deflection of the cupula away from the utricular sac (utriculofugal or ampullofugal) results in excitatory responses in the vertical canals. On the other hand, the kinocilia in the horizontal canals are polarised such that the deflection of the cupula toward the utricular sac (utriculopcdal or ampullopcdal) causes an increase in the neural firing rate.
The response characteristic of the semicircular canals to head movements is dependent on the fluid dynamics of the system. The cupula and the endolymph have identical densities (specific gravity of approximately 1.0). When the head is motionless, the cupula floats in the endolymph, keeping the hairs in their resting positions. The density of neural firing is equal to the sum of tonic inputs from individual nerve fibers. If the head is rotated in the plane of the canal, the canal walls follow the movement of the head; however, the viscosity of the endolymph causes a lag in the motion of the fluid, thus creating a relative motion of the endolymph with respect to the canal wall. Because the cupula completely blocks the flow of endolymph, the fluid motion generates a force across the cupula and bends it in the direction of endolymph flow. If the head rotation continues for an extended period of time at a constant velocity,the cupula eventually returns to its reposition as the fluid motion catches up with the motion of the canal wall. In humans, it takes about 15 to 20 seconds for the cupula to return to its resting position after a sudden change in the head velocity. If the head now is brought to a sudden stop, the relative motion of the endolymph to canal wall will be reversed and the cupula will be bent in the opposite direction. The pattern of neural firing in this case, as well as the sensation experienced by the subject, is the same as if the subject was rotated In the opposite direction of the initial head rotation, given again that the response of the hair cell is bidirectional.
It is clear from this discussion that the stimulus to the semicircular canals is the change in the angular velocity of the head, i.e., in essence, the acceleration of the head along a circular path. The semicircular canals are mostly unresponsive to motion in a straight line. However, the semicircular canals are by no means perfect angular accelerometers. The afferent neural firing pattern is a damped version of the head acceleration and does not exactly match it. The damping effect is due to the combination of inertia and friction posed by the endolymph-cupula dynamics (i.e., due to properties such as mass and viscosity). The neural firing rate nearly perfectly mirrors the head velocity for head movements that consist of brief acceleration and deceleration, with almost no period of constant velocity rotation. For these head movements, which are representative of natural head movements, the semicircular canals act as velocity meters. Another source of deviation from being an ideal accelerometer is the response asymmetry of individual canals for clockwise versus counterclockwise rotations, although asymmetries become apparent only for large-amplitude rotations and are not encountered in our normal daily activities. The asymmetry is due to the differences in the saturation level of excitatory and inhibitory responses of the hair cells. The synergetic pairing of the canals effectively neutralizes the effects of this asymmetry.
The linear motion of the head is not an effective stimulus for the semicircular canal system. Because the cupula and endolymph have the same density, linear accelerations, including gravity, generate little displacement of the cupula. Consequently, the neural activity of the canals produced by linear acceleration of the head is negligible.
The Structure of Otolith Organs
In addition to the crista ampullaris, vestibular sensory cells are found in two other areas: the macula of the saccule and the macula of the utricle. The vestibular receptors formed by these two areas are known collectively as the otolith organs. They respond to an entirely different class of stimuli when compared to the semicircular canals.The utricle and saccule are two cavities within the vestibule. They are filled with cndolymph and each con tains a sensory neuroepithelium, called the macula.
The macula of the utricle is an oval-shaped structure, with its average plane roughly parallel to that of the lateral semicircular canals. The macula of the saccule is also a curved structure, with its average plane roughly parallel to the vertical plane (more accurately, parallel to the sagittal plane bisecting the head). The macula is analogous to the crista in the semicircular canal. It is packed with hair cells and supporting structures necessary for transducing mechanical forces to neural firings. The cilia from the hair cells in each macula protrude into its own otolithic membrane. The otolithic membrane is analogous to the cupula of the canals. It consists of a gelatinous lower surface topped by crystal deposits called otoconia or otoliths. The otoconia are composed of calcium carbonate or calcite deposits of varying size (usually 5 to 7 um). Unlike the cupula, the specific gravity of the otolithic membrane is roughly three times higher than the specific gravity of the endolymph. Both maculae have a thin stripe through the middle of their otolithic membranes called the striola. The otoconia in this area are very small, and the thickness of the otolithic membrane is different compared to the adjacent tissue. In the utricle, the striola is thinner, whereas in the saccule. it is thicker than the surrounding membrane. The striola clearly divides the macula into regions in which the underlying hair cells have different patterns of polarization. Unlike the crista, the hair cells in the macula are not all polarized in the same direction. In the utricle, the hair cells are arranged with their kinocilia pointing toward the striola. In the saccule. the hair cells are aligned with the kinocilia pointing away from the striola. Because both maculae are nonplanar and both striolae are curved, the hair cell activation patterns are complex.The mechanism of stimulation for the otolith organs is any force that displaces the otolithic membrane with respect to the macula. Any arbitrary force applied to the head has two components, one that is parallel, and the other that is perpendicular, to the plane of the macula. The perpendicular component is a compressive force to the hair cells of that macula and therefore does not affect the firing rate of the corresponding afferent neurons. The parallel component, on the other hand, is a shear force that can displace the hair cells and generate neural activity. Because the maculae of the utricle and saccule lie roughly in perpendicular planes, any force component that is compressive to the hair cells in one macula will act as a shear force to the hair cells in the other macula. Therefore, the direction and the magnitude of any force can be decoded by its relative effect on the two maculae.
Because the applied force is proportional to the linear acceleration of the head the otolith organs are assumed to be linear accelerometers. This assumption is somewhat misleading however, because the induced neural activities are complex and not proportional to the linear acceleration of the head. It is more accurate to think of the otoliths as systems that are stimulated by linear acceleration of the head but with highly nonlinear response patterns that are yet to be fully characterized. On earth, the most prominent force of linear acceleration is gravity. Because of the specific configuration of the otoliths. they are intimately involved in detecting the direction of the gravitational vector. This is an important function that allows the vestibular receptors to provide absolute orientation information and distinguishes them from other sensory mechanisms. Clearly, the otolith receptors are capable of sensing dynamic changes of the head velocity, i.e.. acceleration. Because of their sensitivity to gravity, they also are capable of detecting static head lilts. This function is related to the fact that the relative distribution of the gravity vector on the two maculae changes depending on the direction and the magnitude of the head tilt.
The Central Connections of the Vestibular Nerve
The afferent nerve fibers from the semicircular canals and the otolith organs merge to form the vestibular nerve. The vestibular nerve and the auditory nerve are two branches of the eighth (vestibulocochlear) cranial nerve. The eighth and seventh (facial) nerves form a bundle that travels through the internal auditory canal and enters the brainstem lateral to the cerebellopontine angle.Vestibular nerve fibers are bipolar neurons with their cell bodies in Scarpa's (vestibular) ganglion, their peripheral synapses on the hair cells, and their central synapses on the central vestibular structures. Scarpa's ganglion consists of two portions, a superior portion and an inferior portion. The latter comprises the nerve fibers from the crista of the posterior canal and the macula of the saccule. The nerve fibers from the remaining three vestibular receptors (cristae of the lateral and anterior canals and macula of the utricle) as well as a branch of the saccular nerve converge on the superior portion of the Scarpa's ganglion. The vestibular nerve maintains two branches as it leaves the superior and inferior ganglia.
The primary destination of the vestibular nerve fibers is the vestibular nuclei, although some fibers innervate the cerebellum directly . The vestibular nuclei are a group of neurons located mainly in the pons and extending into the medulla. Two sets of nuclei exist, one on the right side and the other on the left side. Each side consists of more than ten distinct groups of neurons . Four of them, the superior, medial, lateral, and descending nuclei, are considered the most prominent ones. Contrary to what is implied by the name, direct vestibular connections constitute only a fraction of the nerve fibers that innervate the vestibular nuclei. Other sources that supply afferent nerve fibers to the vestibular nuclei include the cerebellum, the reticular formation, the spinal cord, and the cervical area. There are also a considerable number of interconnecting fibers between the vestibular nuclei on the right and left sides. The efferent nerve fibers from the vestibular nuclei project to the same parts that supply afferent neurons to them.
As the vestibular neurons enter the brainstem. they take two separate pathways. The ascending pathway terminates either in the superior vestibular nucleus or in the cerebellum, while the descending branch terminates in one of the other three main vestibular nuclei. The vestibular nuclei are the main processors of the vestibular signal where the initial integration of the sensory inputs takes place. The role of the cerebellum is to monitor the vestibular responses and provide adaptive changes as necessitated by the changes in the environmental factors or the properties of the vestibular pathways.
The structures of the central vestibular pathways are an order of magnitude more complex than the peripheral. Significant gaps remain in our understanding of these pathways. Nonetheless, a brief discussion of the VOR and VSR is valuable for clinical assessment and management of vestibular disorders. The VOR pathways make two distinct connections between the vestibular nuclei and oculomotor neurons: a direct one using the nerve fibers in the medial longitudinal fascicules and an indirect one mediated through the reticular formation. The precise control of vestibuiar-driven eye movements requires coordinated activities of both pathways. Regardless of their pathway, project to the oculomotor nuclear complex: the third (oculomotor), the fourth (trochlear). and the sixth (abducens) nucleus, each nucleus is composed of a pair of cell groups, one on each side of the brain midline. Excitatory responses from one side usually are coupled with inhibitory responses from the opposite side to generate conjugate eye movements. The motor neurons from the oculomotor nuclei drive three pairs of extraocular muscles in each eye. The muscle pairs are arranged to move the eye in planes that roughly coincide with the planes of the semicircular canals. This arrangement simplifies the task of generating compensatory eye movements in response to head motion by enabling one pair of canals to drive only one pair of extraocular muscles. A functional description of the VOR pathways is provided in the next section The VSR pathways are far more complex than those of the VOR. This is not surprising considering that the task of postural control requires regulation of the activities of many more muscles and joints and integration of more complex sensory signals. The VSR is not a single reflex as is the VOR, but rather it is composed of a series of context-sensitive reflexes that are initiated on the basis of the available sensory inputs and the required motor task. The anterior horn cells of the spinal cord are the motor neurons that control the activities of the skeletal muscles. These motor neurons are connected to the vestibular nuclei via three primary pathways: the lateral vestibulospinal tract, the medial vestibulospinal tract, and the rcticulospinal tract. The first two trac project directly from the secondary vestibular neurons, whereas the third tract projects indirectly from the reticular formation that receives input from the vestibular nuclei. All three tracts are highly influenced by the cerebellum..
Functional Organization of Vestibilar Response
Stimulation of the Semicircular Canals: Responses to Head Rotation
An important function of the vestibular system is to participate in generating compensatory eye movements to maintain clear vision during head movements. The primary role of the semicircular canals is to detect rotational acceleration of the head. When the head undergoes an angular acceleration in the plane of one of the canals, the firing rate of the afferent nerve fibers changes accordingly. The characteristics of vestibular responses to rotation is highly influenced by synergistic pairing of the canals. Any head motion that generates an excitatory response in one canal also generates an equal inhibitory response from the paired canal in the opposite labyrinth. This type of arrangement is referred to as a push-pull organization in the engineering literature.There are a number of advantages to the push-pull organization of the canal responses. First, it improves the resolution of the system by supplying the CNS with a signal that is twice as large as that produced by a single canal. Second, it desensitizes the system to changes in the afferent neural firing that are not produced by head motion. For example, changes in the body temperature or the chemical composition of the inner ear fluids alter the tonic activity of the vestibular neurons from a single canal. However, because these changes affect both labyrinths simultaneously, they are not falsely perceived as signals generated by head motion. Third, the push-pull arrangement of the canals provides a level of redundancy such that a failure of one labyrinth does not completely impair the vestibular function. Finally, this arrangement effectively neutralizes the inherent asymmetry between the excitatory and inhibitory responses of a single canal. High acceleration stimuli in one direction that saturate the inhibitory response of one canal will induce a similar saturation in the output of the paired canal for rotation in the opposite direction. Thus, the net input to the central vestibular pathways is the same regardless of the direction.
The process for generating compensatory eye movements in response to head rotation can be best illustrated by considering rotations in .the plane of the lateral semicircular canals. The arrangement of the hair cells in the lateral canals is such that the neural firing from the leading ear (the left ear. in this ease) increases, whereas (he firing rate from the opposite side decreases from its tonic level. For most normal dailv activities, the magnitude of the asymmetry between the responses from the two sides is proportional to the head velocity. This asymmetry is a signal to the central vestibular pathways to drive the eyes in the opposite direction of the motion with an amplitude that matches the head velocity.
To understand how neural activities from the peripheral vestibular system are converted to compensator eye movements, one must become familiar with the way oculomotor pathways generate eye movements in general. The neural command to the ipsilateral paramedian pontine reticular formation (PPRF) is a short-duration sudden surge in the firing rate (excitation pulse). The contralateral PPRF simultaneously receives a sudden decrease in the firing rate of the input neurons (inhibitory inverse pulse). Three pairs of muscles in each eye are used to move the eye in three different planes. The lateral rectus muscle and the medial rectus muscle move the eyes in the horizontal plane. For movements in any direction, one muscle contracts to pull the eye in the direction of movement (agonist muscle) while the paired muscle relaxes to allow movement in the opposite direction (antagonist muscle). For a rightward eye movement, the right lateral rectus and the right medial rectus muscles act as agonists and the right medial and left lateral rectus muscles act as antagonists. The excitatory pulse and inhibitory inverse pulse to the PPRF are transformed as they travel through the medial longitudinal fasciculus and oculomotor nuclei before supplying the muscles via the motor neurons. The agonist muscles receive a sudden increase in the neural firing rate followed by a drop to a new level that is slightly higher than the initial firing rate of the neurons (pulsestep), The pulse provides the muscle contraction to move the eyes quickly to the new position and the step allows the increased level of contraction required to keep the eyes in the new position. Similarly, the antagonist muscles receive an inverse pulse-step to provide the necessary muscle relaxation for initiating the eye movement and maintaining the new eye position. The responses of the oculomotor system to other stimuli can be inferred from the eye movements generated by the pulse command to the PPRF. Of particular interest are the stimuli generated by the secondary vestibular neurons from the vestibular nuclei. The afferent vestibular signal in response to an angular acceleration of the head is an increase in the firing rate of neurons from the leading ear and a decrease of firing rate from the opposite ear. For natural head movements, the excitatory neural tiring rate is approximately a triangular waveform resembling the head velocity. Unlike the pulse That, when applied to the PPRF, causes a quick change the eye position, the triangular waveform results in a slow drift of the eye from one position to another. The speed of the eye movement is proportional to the rate of the increase in neural firing and, consequently, to the velocity of the head. The signals from the vestibular nuclei cross the midbrain and connect to the ipsilateral PPRF. Thus, the response to a brief head action is a movement of the eyes in the opposite direction of head motion. Because the eye velocity matches head velocity, the eyes will remain virtually stationary in space.
When the head rotation is sustained, (he asymmetry in firing rate of the right-left vestibular neurons persists a much longer time. If there were no other intervention, the eyes would drift slowly in the opposite direction, :h their orbital limits, and remain in that position until neural asymmetry subsided. Because such a response ot desirable for maintaining a stationary image on the retina, a pulse is applied to the PPRF to move the eyes back toward the midline. The drift and the subsequent resetting of the eyes continue as long as the neural asymmetry persists. The source of the pulse is most likely the pulse generator in the saccadic system, which is responsible for moving the eyes quickly from one target to another. Intuitively, one might assume that eyes must reach the limit of the orbit before the pulse resets them to the center. In humans, however, the occurrence of the pulse appears to depend on the position and velocity of the eyes and can occur well in advance of the eyes reaching their limit. In other words, the pulse generator is triggered by an anticipatory process that keeps the eyes near the mid-line at all times. The specific to-and-fro pattern of eye movements generated by vestibular stimulation belongs to the class of eye movements known as nystagmus.
The studies of oculomotor responses mediated by the vertical semicircular vanals have been limited because of the complexity of the instruments needed to generate vertical stimuli as well as technical difficulties in recording vertical eye movements. Yet it is clear that the rotation of the head in the plane of the vertical semicircular canals does generate compensatory eye movements in that plane. The neural process, however, is complicated because the orientation of the planes of the semicircular canals and eye muscles is somewhat different. Therefore, the spatial information from the canals must be mapped on the coordinates of the eye muscles through a transformation. Such a transformation occurs as the semicircular canal output travels through the vestibular and oculomotor nuclei.
Vetibular Nystagmus
Nystagmus is a rhythmic to-and-fro eye movement typically identified by a slow drift of the eyes in one direction followed by a fast reset in the opposite direction. In case of vestibular nystagmus, the slow component is generated by the VOR while the fast component is generated by the pulse generator of the saccadic system. Because the firing rate of the vestibular neurons does not change significantly during each nystagmus beat (approximately 1 second or less), the slow phase of vestibular nystagmus is linear. That is, the slow-phase velocity is relatively constant during each nystagmus beat. Nystagmus is characterized by its fast phases. Thus, right-beating nystagmus indicates slow leftward eye movements followed by fast rightward phases. When nystagmus is provoked by head motion, the nystagmus typically beats in the direction of the acceleration. For instance acceleration toward the left ear (counterclockwise rotation) causes left-beating nystagmus. Note that if the subject is brought to a sudden stop after prolonged constant-velocity counterclockwise rotation, the resulting nystagmus will be right-beating because deceleration of the head is equivalent to accelerating the head in the opposite direction of the initial rotation.In addition to the acceleration of the head, two other conditions are necessary to observe vestibular nystagmus. First, the type of eye movements can be observed only in the absence of vision (eyes closed or in darkness). With vision present, other visual mechanisms. namely, the optokinetic and tracking systems, interact with the vestibular responses in generating compensatory eye movements. In the example in which the subject is suddenly stopped after a prolonged rotation, vestibular nystagmus can be observed in darkness. However. when vision is permitted, vestibular nystagmus is quickly suppressed. This is functionally reasonable because, in the absence of head motion, such compensatory eye movements are not required. The second condition for the formation of vestibular nystagmus is the mental alertness of the subject. Alertness appears to be necessary only for generating the fast phase of the nystagmus. It has been demonstrated that vestibular stimulation in comatose individuals does produce the slow drift of the eyes . However, once the eyes reach the periphery of the orbit, they remain deviated to one side.
An important property of the VOR pathways is revealed by examining eye movement responses during a prolonged constant-velocity rotation. The canal response consists of a sudden change in the firing rate of the peripheral neurons, which returns to its baseline exponentially as the cupula returns to its resting position. The intensity of the resulting vestibular nystagmus (slow-phase velocity) also undergoes a similar pattern, rising immediately after the initiation of motion and dissipating exponentially over time. However, there is a significant difference between the time course of the two events. Whereas the canal responses disappear after 15 to 20 seconds, the nystagmus persists almost three times longer. The prolongation of the nystagmus is due to a neural integrator aptly named the velocity storage mechanism. The integrator acts as a storage tank in which an outflow valve can control the flow of neural activity so that it is not as rapid as the inflow. Consequently, there is a buildup of the neural activity that continues even after the input signal has ceased. The overall effect of the velocity storage mechanism is to extend the frequency response of the VOR pathways to lower frequencies. The gain (ratio of slow-phase eye velocity to head velocity) and phase (temporal difference of slow-phase eye velocity to head velocity) are shown for different frequencies of sinusoidal head movements. For ideal compensatory eye movements, the slow-phase eye velocity will be exactly the same amplitude as the head velocity but in the opposite direction. The frequency responses show the deviation of the resulting eye movements from ideal ones for different frequencies. When the gain is equal to one and the phase is equal to zero, the eye movements are completely compensatory. Without the velocity storage mechanism, the ideal responses are limited to the frequency range from 0.3 to 10 Hz. For frequencies lower than 0.3 Hz, the slow-phase eye velocity is less than the head velocity (gain less than one), and there is a time difference between the two (phase greater than zero). With the addition of the velocity storage mechanism, the effective range of the canal-ocular responses is extended to 0.1 to 10 Hz.
Stimulation of the Semicircular Canals: Responses to Temperature Gradients
The natural mode of stimulation for vestibular receptors is head motion; however, nonphysiologic stimuli are common in clinical testing of the vestibular system. In particular, the caloric test is still one of the most effective means of assessing vestibular function because it permits stimulation of each labyrinth independently. The caloric testing is administered with the subject in a supine position with the head bent forward by 30 degrees. With the head in this position, the lateral semicircular canals are placed in the vertical plane. If a significant temperature gradient develops between the endolymphatic fluid on one side of the canal with respect to the fluid on the opposite side, the endolymph will begin to move, thus displacing the cupula. Such a temperature gradient can be induced by irrigating the external auditory canal with a medium (air or water) that has a significantly different temperature when compared to the body temperature.The underlying mechanism for the movement of the endolymph during caloric irrigations is the temperature-induced change in the density of the endolymph. For example, a warm stimulus causes the fluid closest to the auditory canal to become lighter than the rest of the endolymph and rise due to the effect of gravity. This causes an excitatory response of the afferent neurons from the irrigated ear. The asymmetry between the neural firing rates from the two labyrinths is identical to that produced by the horizontal angular acceleration of the head toward the irrigated ear. Similarly, the resulting vestibular nystagmus has the same characteristics as those described earlier. A cold irrigation of the ear results in the flow of the endolymph in the opposite direction and decreases the neural firing rate of the irrigated ear. An acronym, COWS (cold opposite, warm same), is used to quickly identify the direction of the nystagmus generated by different irrigations. For example, cool irrigation of the left ear causes right-beating nystagmus exactly the same way as if the patient was being accelerated toward the right ear. It is clear from this discussion that gravity is essential to explain the theory for generation of caloric responses. However, experiments in the space shuttle in the early 1980s cast doubt on the validity of this assumption when caloric responses were apparently produced in the absence of gravity. Yet compelling evidence remains to support the explanation. Warm irrigation of the external auditory canal in this head position generates ampullofugal flow and decreases the neural firing rate from the irrigated side. The change in the direction of the nystagmus when the subject moves from supine to prone or from prone to supine can be interpreted only by considering die reversing the gravity vector. Today, the general is that gravity is primarily responsible for caloric responses, although small changes m d rate of the neurons can be attributed to the direct the temperature on the afferent nerve fibres.
Caloric responses are mediated primarily by the lateral semicircular canals. Theoretically, it also is possible to generate caloric responses from vertical canals if they are placed in the plane of gravity. However, the anatomic organization of the labyrinths is such that the vertical semicircular canals are distant from the external auditory canal. As a result, it is not possible to create the temperature gradient necessary to generate adequate vestibular stimulation for the vertical canals.
Stimulation of the Otolith Organs
The maculae of the utricle and saccule transduce forces applied to the head into neural signals. In contrast to the semicircular canals, the otolith organs respond to dynamic changes in linear velocity as well as static changes in the orientation of the head. The sensitivity of the otoliths to head tilts is due to presence of the gravitational field, which imposes a constant linear acceleration. Although only two sensory receptors are available for linear motion, the distinct arrangement of the macular hair cells allows the otoliths to sense motion in all three dimensions. This same arrangement also is responsible for creating synergistic pairing of the otoliths that is much more complex than that e canals. In otoliths, the push-pull arrangement might be confined to only one area of the macula on each side instead of involving the entire sensory organ.As is the case for the semicircular canals, stimulation of the otoliths also is expected to produce compensatory eye movements. Electrical stimulation of the utricular and saccular nerve fibers, as well as direct stimulation of macular regions, produce steady eye deviations. The direction of the eye deviations depends on the polarization hair cells in each region. Nystagmus eye movements have been reported, but it is not clear whether nystagmus responses were the result of inadvertent stimulation of semicircular canal nerve fibers .
When otolith stimulation is generated by head tilts, the resulting eye movements can be either torsional (rotation of the eyes in the orbit about the visual axis) or rotational (similar to horizontal eye movements but may include a vertical component). The type of response is different among species and depends on the orientation of eyes and the direction of tilt. In humans, lateral head tilts generate torsional eye movements known as ocular counter-rolling. Although these eye movements are compensatory, they are not efficient in counteracting the effect of head tilts. The amplitude of eye torsion even for large tilts is only around 10% of the amplitude of the head tilt. Head lilts in the pitch plane generate vertical movements of the eves. However, the effect of the vertical semicircular canals in generating such eye movements during the acceleration phase of the tilt should not be overlooked.
The effect of linear head acceleration in generating compensatory eye movements is more controversial. If the otoliths are viewed as sensors that respond to the combination of all forces applied to the head, then compensatory eye movements for linear acceleration in the lateral plane (along the interaural axis) will be ocular counterrolling similar to those generated by lateral head tilts. Instead, experiments using such an acceleration have produced horizontal nystagmus. Similarly, linear accelerations in the pitch plane ( along the occipitonasal axis) have failed to produce vertical eye movement as expected. These observations indicate that the otolithocular pathways do not respond the same way to other linear accelerations as they vestibular receptors is to complement the visual system. This can be best accomplished if gravity is treated differently than other linear accelerations that induce motion.
Overall, otolith-induced eye movements are not studied as extensively as those produced by the semicircular canals. Significant gaps remain in our understanding of the organization and the exact function of the otolith-ocular pathways.
Adaptation of Vestibular Responses
A discussion of vestibular function is incomplete without consideration of the role of adaptation. Adaptation is the process of making adjustments to the vestibular pathways to improve their performance under a variety of conditions. The cerebellum is thought to be the origin of the adaptive control mechanisms. These mechanisms are part of a more global compensation system that is responsible for recovering from a vestibular lesion. Whereas compensation can take many different forms (see the next section), adaptation primarily involves changing the sensitivity (gain) of the vestibular pathways. It should be noted, however, that because the VOR is a dynamic system, changing the gain means more than simply changing the intensity of the eye movements. Other response characteristics, such as timing and direction of eye movements, also may be affected.As noted before, normal vestibular responses usually are short in duration, often lasting only a few seconds. When the asymmetry from right-left afferent nerve fibers persists for longer than the anticipated time, the sensitivity of the VOR, and consequently the intensity of the nystagmus is reduced. This adjustment can take place in a relatively short period of time. For example, if caloric stimulation is applied for an extended period of time, the adaptive changes can begin within a few minutes. Similarly, repeated stimulation of the vestibular system can activate the adaptive mechanisms. For example, the intensity of induced nystagmus declines after repeated exposure to rotation. A more drastic example of adaptation occurs during space flights. Removal of the gravitational vector causes a change in the firing pattern of the otolith neurons. Whereas a change in the gain of the VOR may be helpful in the short term to alleviate motion sickness symptoms, a more intricate change in the organization of the otolith pathways is needed to deal with the long-term consequences of space flight on the vestibular system. Once the astronauts return to earth, a similar reorganization must take place to adapt to gravity.
Effects of Peripherial Vestibular Lesions
Peripheral vestibular disorders are the major cause of dizziness and balance disorders in humans. Understanding the underlying process of vestibular pathologies and central compensation mechanisms can provide a significant insight into the assessment and management of dizzy patients. The scope of peripheral vestibular disorders can be best appreciated by an abstract analysis of the problem. The vestibular system consists of ten receptors, live per labyrinth. If one assumes each receptor can develop a lesion independently, there will be more than 1,000 combinations of ways that the vestibular receptors may become dysfunctional. This simple analysis does not include damage to the surrounding support structures and many other aspects of lesions, such as complete versus partial, transient versus permanent, or sudden versus gradual. Also not considered is the differentiation of the type of lesion that impairs receptor function from the type of lesion that distorts function.-' Therefore, one should not be surprised by the myriad of the symptoms reported by patients with diseases of the labyrinths and the vestibular nerve. It is humbling to consider that our assessment methods can only evaluate a handful of peripheral vestibular anomalies.Effects of Unilateral Vestibular Lesions
A unilateral peripheral lesion can be caused by a disease process that destroys the hair cells in the labyrinth or directly affects the peripheral nerve function. The unilateral decrease in the tonic neural activity results in an asymmetry identical to that produced by head rotation. The patient perceives the head rotating toward the intact ear. This illusion of motion is called vertigo. In this case, because there is a conflict between the information from the vestibular system and those from other sensory modalities, the patient will likely experience vegetative symptoms associated with such a sensory conflict, such as nausea and vomiting. Additionally, the patient will have vestibular nystagmus, which has similar characteristics to those produced in response to physiologic stimuli and described in the previous section. This pathologic nystagmus is often referred to as spontaneous nystagmus to highlight that it is present in the absence of head motion. However, in this chapter, this often misused terminology is avoided because the same term also is used to describe any pathologic nystagmus regardless of its origin or characteristics.The sudden unilateral loss of labyrinthine function produces vestibular nystagmus that is predominantly horizontal but sometimes also has a torsional component. The horizontal component of the nystagmus is caused by the loss of tonic activity from the afferent neurons of the lateral canal on the damaged side. The slow phase of this nystagmus will be directed toward the damaged side because the CNS perceives the head rotation being toward the intact ear. It should be noted, however, that the direction of nystagmus can change because of vestibular compensation and is not always a reliable indicator of the side of lesion (see followmu). Pathologic vestibular nystagmus does not have a vertical component. Vertical eye movements that are generated by the vertical semicircular canals from one ear in the opposite direction. The net result is the cancellation vertical component because the anterior and posterior canals from the intact side have no functioning match in the damaged side. These canals produce torsion eye movement that are in the same direction, thus explaining the torsional component of the nystagmus .
Acute unilateral vestibular loss also causes other postural abnormalities, including head tilt toward the side of lesion disequilibrium. Many of these effects are temporary and recover quickly after compensation. One manifestation of unilateral vestibular loss, which seems to persist permanently, is a static torsion of the eyes toward the side of lesion. This ocular tilt reaction is likely caused by the unilateral loss of otolithic function.
Vestibular Compensation After a Unilateral Vestibular Lesion
The persistent asymmetry in the firing rate of vestibular neurons triggers the vestibular compensation mechanisms. In this case, vestibular compensation consists of distinct processes. First, the static balance in the tonic neural activities of the two labyrinths is restored. Second, the characteristics of the vestibular pathways (e.g., sensitivity or gain) are modified to accommodate dynamic changes due to the loss of motion-induced neural activities from one labyrinth.The asymmetry in the neural firing rates immediately after a sudden unilateral vestibular loss is reduced by "clamping" the neural activity of the intact labyrinth . This step can begin within days, if not hours, after the initial damage to the labyrinth. The increase in the asymmetry of neural activities reduces the intensity of the symptoms. The effect is similar to that of the antivertiginous medications that suppress the vestibular activity at the brainstem level. Within 1 week after the onset of the lesion, neural activity appears in the vestibular nuclei at the site innervated by the afferent nerve fibers from the damaged side. This neural activity originates not from the labyrinth, but from other sources within the CNS. At the same time, the activity from the tact side begins to increase as the clamping of the vestibular input is eased. After a few weeks, the static condensation is completed when the tonic neural firing from intact side returns to its prelesion level and the neural activity is restored at the vestibular nuclei of the damaged. The static compensation process occurs regardless of whether the unilateral vestibular loss is sudden or gradual. In case of a gradual loss, the entire compensation process takes place repeatedly in small increments. As a result, a patient with such a loss may not experience the kind of severe symptoms associated with a sudden unilateral lesion.
After a unilateral vestibular loss, the inherent asymmetry between the excitatory and inhibitory neural firings from one semicircular canal is no longer offset by the responses from the paired canal. Therefore, it is expected that the responses for clockwise and counterclockwise rotations will be asymmetric after a unilateral lesion. In practice, this type of asymmetry is seen only in the early stage of static compensation during the period when the responses from the intact ear are suppressed. In this stage, rotation away from the side of lesion will quickly saturate the response as the neural firing rate is reduced to zero. The rotation toward the intact side will be unaffected as the excitatory responses can increase significantly more. After the completion of static compensation, the response asymmetries can be seen only for high-acceleration stimuli.
The process of static compensation is most effective when the lesion is stable. Fluctuations in the status of the labyrinth disrupt the compensation process and cause symptoms that usually are more troublesome to the patient than those caused by a stable lesion, even when the lesion is permanent. If function is restored to the damaged labyrinth during the compensation steps for which the neural activity of the intact side is suppressed, the asymmetry in the neural activity of right-left labyrinths will be reversed. This reversal leads to eye movements known as recovery nystagmus. The slow phase of the recovery nystagmus is in the opposite direction of the slow phase of the nystagmus seen immediately after an acute vestibular lesion. Otherwise, the two types of nystagmus have identical characteristics and cannot be differentiated. Therefore, one cannot rely solely on the direction of the nystagmus as an indicator of side of lesion.
It is clear that head rotation will generate the neural asymmetry necessary for detecting the direction of rotation. However, the magnitude of the asymmetry is half of that generated by two functioning labyrinths for the same head acceleration. During the dynamic phase of compensation, the vestibular pathways are recalibrated such that the new pattern of the head velocity to neural firing rates is transformed into compensatory eye movements with appropriate intensities. Intuitively, the gain of the VOR pathways must be doubled to generate the same amplitude of eye movements as those generated before the lesion. However, because the VOR is a dynamic system, a change in the gain of the pathway could affect other characteristics, including its frequency response. Recall the analogy used for the velocity storage mechanism. One way to increase the sensitivity is to increase the gain of the integrator in the VOR pathway. This is analogous to increasing the outflow of the velocity storage mechanism. Although this action increases the sensitivity, it also diminishes the storage capacity of the integrator. Consequently, the low-frequency performance of the system will be degraded..
Degradation of low-frequency VOR performance is associated with unilateral loss of vestibular function. Rotational tests in patients with such lesions show that the ratio of the slow-phase eye velocity to head velocity decreases and the phase difference between them increases for low frequencies. However, the process of dynamic compensation is more complex than simply increasing the gain of the VOR. Most likely, a remapping of the vestibular signals is necessary to ensure precise integration of the information from all sensory mechanisms.
Effects of Bilateral Vestibular Lesions
Bilateral vestibular lesions are far less common than unilateral ones. Although the long-term functional consequences of bilateral lesions are considerably more serious, ironically, the symptoms are not as severe as those after a sudden unilateral lesion. Because there is no asymmetry between the right-left neural firing rates, patients with bilateral lesions do not experience vertigo, nystagmus, or vegetative symptoms. The main complaints of these patients are disequilibrium and oscillopsia. Oscillopsia is the illusion that stationary objects are moving during head motion. This symptom is caused by the impairment of the VOR after loss of both labyrinths. Because vestibular-driven compensatory eye movements are no longer possible, the images of the objects are not stationary long enough to have clear vision during head motion.Bilateral vestibular lesions can be complete or partial. The loss of function for partial lesions is confined to low-frequency head movements, whereas the high-frequency responses are preserved until the loss is complete. In the case of a complete vestibular loss, there is no vestibular-mediated' mechanism to restore function. Instead, the central compensation mechanisms utilize other sensorimotor inputs to substitute for the labyrinthine function. The visual and neck receptors are the most appropriate alternatives for both postural and visual stabilization. The compensation methods for bilateral lesions are not nearly as effective as the methods described for unilateral lesions. Patients with complete and permanent bilateral lesions are not as likely to regain their prelesion functional status as well as patients with a unilateral loss.
Conclusion
- The vestibular receptors are responsible for sensing the three-dimensional orientation and movements of the head.
- The information from the vestibular system is used by the VSR and VOR to maintain a stable upright posture and to provide clear vision during head movements.
- Three semicircular canals in each labyrinth respond to rotational movements of the head and generate an afferent neural firing pattern that is a damped version of the head acceleration. For natural head movements, the neural firing rate is proportional to the head velocity.
- When the head undergoes an angular acceleration in the plane of one of the semicircular canals, the firing rate of the afferent nerve fibers from the leading ear increases, whereas the firing rate from the opposite side decreases from its tonic level.
- The asymmetry in the firing rate of the right-left vestibular neurons generates compensatory eye movements known as nystagmus. When nystagmus is provoked by head rotation, its slow phase is in the opposite direction of the head acceleration.
- The role of otolith organs, the maculae of utricle and saccule, is to sense linear accelerations of the heads. Because of their sensitivity to gravity, the otoliths also are responsible for detecting the static orientation of the head.
- Caloric stimulation of the labyrinth in the standard caloric position (head tilted forward 30 degrees from the supine position) causes movement of the endolymph and changes the neural firing rate from the irrigated ear. A cold irrigation of the ear decreases the firing rate, whereas a warm irrigation increases it.
- An acronym, COWS (cold opposite, warm same), is used to identify the fast phase of the nystagmus generated by different irrigations in the standard caloric position.
- The unilateral loss or reduction of labyrinthine function produces vertigo and vestibular nystagmus. For acute lesions, the perceived head rotation is toward the intact ear and the slow phase of the nystagmus is directed toward the damaged side.
- The persistent asymmetry in the firing rate of vestibular neurons after a unilateral vestibular loss triggers vestibular compensation mechanisms. These mechanisms restore the balance in the tonic neural activities (static compensation and modify the vestibular pathways to accommodate for the loss of motion-induced neural activities from one labyrinth (dynamic compensation).