Otolith Input Research Articles

Neurobiology of fish under altered gravity conditions

In vertebrates (including man), an altered gravitational environment such as weightlessness can induce malfunction of the inner ear, based on an irregular dislocation of the otoliths from the corresponding sensory epithelia. This dislocation leads to an illusionary tilt, since the otolithic inputs are not in register with other sensory organs. This results in an intersensory conflict. Vertebrates in orbit therefore face severe orientation problems. In humans, the intersensory conflict may additionally lead to a malaise, commonly referred to as space motion sickness (SMS). During the first days in weightlessness, the orientation problems (and SMS) disappear, since the brain develops a new compensatory interpretation of the available sensory data. The present review reports the neurobiological responses—particularly in fish—observed at altered gravitational states, concerning behaviour and neuroplastic reactivities. Recent investigations employing microgravity (spaceflight, parabolic aircraft flights, clinostat) and hyper-gravity (laboratory centrifuges as ground based research tools) yielded clues and insights into the understanding of the respective basic phenomena. The possible sources of human space sickness (a kinetosis) and of the space adaptation syndrome (when a sensory reinterpretation of gravitational and visual cues takes place) are particularly highlighted with regard to the functional significance of bilaterally asymmetric otoliths (weight, size).

Human horizontal vestibulo-ocular reflex initiation: effects of acceleration, target distance, and unilateral deafferentation.

The vestibulo-ocular reflex (VOR) generates compensatory eye movements in response to angular and linear acceleration sensed by semicircular canals and otoliths respectively. Gaze stabilization demands that responses to linear acceleration be adjusted for viewing distance. This study in humans determined the transient dynamics of VOR initiation during angular and linear acceleration, modification of the VOR by viewing distance, and the effect of unilateral deafferentation. Combinations of unpredictable transient angular and linear head rotation were created by whole body yaw rotation about eccentric axes: 10 cm anterior to eyes, centered between eyes, centered between otoliths, and 20 cm posterior to eyes. Subjects viewed a target 500, 30, or 15 cm away that was extinguished immediately before rotation. There were four stimulus intensities up to a maximum peak acceleration of 2,800 degrees/s2. The normal initial VOR response began 7-10 ms after onset of head rotation. Response gain (eye velocity/head velocity) for near as compared with distant targets was increased as early as 1-11 ms after onset of eye movement; this initial effect was independent of linear acceleration. An otolith mediated effect modified VOR gain depending on both linear acceleration and target distance beginning 25-90 ms after onset of head rotation. For rotational axes anterior to the otoliths, VOR gain for the nearest target was initially higher but later became less than that for the far target. There was no gain correction for the physical separation between the eyes and otoliths. With lower acceleration, there was a nonlinear reduction in the early gain increase with close targets although later otolith-mediated effects were not affected. In subjects with unilateral vestibular deafferentation, the initial VOR was quantitatively normal for rotation toward the intact side. When rotating toward the deafferented side, VOR gain remained less than half of normal for at least the initial 55 ms when head acceleration was highest and was not modulated by target distance. After this initial high acceleration period, gain increased to a degree depending on target distance and axis eccentricity. This behavior suggests that the commissural VOR pathways are not modulated by target distance. These results suggest that the VOR is initially driven by short latency ipsilateral target distance dependent and bilateral target-distance independent canal pathways. After 25 ms, otolith inputs contribute to the target distance dependent pathway. The otolith input later grows to eventually dominate the target distance mediated effect. When otolith input is unavailable the target distance mediated canal component persists. Modulation of canal mediated responses by target distance is a nonlinear effect, most evident for high head accelerations.

Immersed False Vertical Room

We evaluated a new model of motion sickness--an enclosure decorated with visual cues to upright which was immersed either inverted or "front"-wall down, in Johnson Space Center's Weightless Environment Training Facility (WETF) pool. This "WETF False Vertical Room" (WFVR) was tested with 19 male and 3 female SCUBA diver subjects, aged 23 to 57, who alternately set clocks mounted near the room's 8 corners and made exaggerated pitch head movements. We found that (1) the WFVR test runs produced motion sickness symptoms in 56% and 36% of subjects in the room-inverted and room-front-down positions, respectively. (2) Pitch head movements were the most provocative acts, followed closely by setting the clocks--particularly when a clock face filled the visual field. (3) When measured with a self-ranking questionnaire, terrestrial motion sickness susceptibility correlated strongly (P < 0.005) with WFVR sickness susceptibility. (4) Standing instability, measured with a modified Fregly-Graybiel floor battery, also correlated strongly (P < 0.005) with WFVR sickness susceptibility. This result may reflect a relationship between visual dominance and WFVR sickness. (5) A control study demonstrated that the inverted and front-down positions produced WFVR sickness, but the upright position did not, and that adaptation may have occurred in some subjects with repeated exposure. The WFVR could become a useful terrestrial model of space motion sickness (SMS) because it duplicates the nature of the gravity-dependent sensory conflicts created by microgravity (visual and otolith inputs conflict while somatosensory gravity cues are minimized), and it also duplicates the nature of the provocative stimulus (sensory environment "rule change" versus application of motion to passive subject) more closely than any other proposed terrestrial SMS model. Also, unlike any other proposed terrestrial SMS model, the WFVR incorporates whole-body movement in all three spatial dimensions. However, the WFVR's sensory environment differs from that created by spaceflight in several respects, including the presence of frictional drag on limb movement, magnification at the face-mask-water interface, greater otolith conflict, exhaled bubbles, and the presence of some gravity-dependent somatosensory inputs.

Tilt perception during dynamic linear acceleration.

Head tilt is a rotation of the head relative to gravity, as exemplified by head roll or pitch from the natural upright orientation. Tilt stimulates both the otolith organs, owing to shifts in gravitational orientation, and the semicircular canals in response to head rotation, which in turn drive a variety of behavioral and perceptual responses. Studies of tilt perception typically have not adequately isolated otolith and canal inputs or their dynamic contributions. True tilt cannot readily dissociate otolith from canal influences. Alternatively, centrifugation generates centripetal accelerations that simulate tilt, but still entails a rotatory (canal) stimulus during important periods of the stimulus profiles. We reevaluated the perception of head tilt in humans, but limited the stimulus to linear forces alone, thus isolating the influence of otolith inputs. This was accomplished by employing a centrifugation technique with a variable-radius spinning sled. This allowed us to accelerate the sled to a constant angular velocity (128 degrees/s), with the subject centered, and then apply dynamic centripetal accelerations after all rotatory perceptions were extinguished. These stimuli were presented in the subjects' naso-occipital axis by translating the subjects 50 cm eccentrically either forward or backward. Centripetal accelerations were thus induced (0.25 g), which combined with gravity to yield a dynamically shifting gravitoinertial force simulating pitch-tilt, but without actually rotating the head. A magnitude-estimation task was employed to characterize the dynamic perception of pitch-tilt. Tilt perception responded sluggishly to linear acceleration, typically reaching a peak after 10-30 s. Tilt perception also displayed an adaptation phenomenon. Adaptation was manifested as a per-stimulus decline in perceived tilt during prolonged stimulation and a reversal aftereffect upon return to zero acceleration (i.e., recentering the subject). We conclude that otolith inputs can produce tilt perception in the absence of canal stimulation, and that this perception is subject to an adaptation phenomenon and low-pass filtering of its otolith input.

Neurobiological responses of fish to altered gravity conditions: A review

In vertebrates (including man), altered gravitational environments such as weightlessness can induce malfunctions of the inner ears, based on an irregular dislocation of the inner ear otoliths from the corresponding sensory epithelia. This dislocation leads to an illusionary tilt, since the otolithic inputs are not confirmed by the other sensory organs, which results in an intersensory conflict. Vertebrates in the orbit therefore face severe orientation problems. In humans, the intersensory conflict may additionally lead to a malaise, commonly referred to as space motion sickness (SMS). During the first days at weightlessness, the orientation problems (and SMS) disappear, since the brain develops a new compensatory interpretation of the available sensory data. The present review reports on the neurobiological responses — particularly of fish — observed at altered gravitational states, concerning behaviour and neuroplastic reactivities.

Topography and reciprocal activity of cerebellar Purkinje cells in the uvula-nodulus modulated by vestibular stimulation.

In the rabbit uvula-nodulus, vestibular and optokinetic information is mapped onto parasagittal zones by climbing fibers. These zones are related functionally to different pairs of vertical semicircular canals, otolithic inputs and horizontal optokinetic inputs. Vestibular stimulation restricted to one of these zones modulates climbing fiber responses (CFRs). Within each of these zones, simple spikes (SSs) are modulated reciprocally with CFRs. In rabbits anesthetized with chloralose-urethan, we have used vestibular and optokinetic stimulation to evoke CFRs within a parasagittal zone while recording from Purkinje cells in adjacent zones. We have examined whether the CFRs evoked by vestibular stimulation in one zone influence the SSs of an adjacent zone. CFRs and SSs were recorded during roll vestibular stimulation. The orientation of the head of the rabbit with respect to the axis of rotation was varied systematically so that a climbing fiber null plane could be determined. This null plane was the orientation of the head about the vertical axis at which no modulation of the CFR was observed during rotation about the longitudinal axis of the vestibular rate table. In the left uvula-nodulus, a medial sagittal strip extending through all the folia contained Purkinje cells with CFRs that had optimal planes of stimulation coplanar with the left posterior-right anterior semicircular canals (LPC-RAC). Lateral to this strip was a strip of Purkinje cells with CFRs that were characterized by optimal planes corresponding to stimulation of the left anterior-right posterior semicircular canals (LAC-RPC). SSs in Purkinje cells were modulated out of phase with CFRs from the same Purkinje cell. The depth of modulation of both CFRs and SSs was reduced during rotation in the climbing fiber "null plane". The depth of modulation of SSs was greatest when recorded from Purkinje cells located at the center of semicircular canal-related strip. We observed that 1) all folia of the uvula-nodulus receive vestibular climbing fiber inputs; 2) these climbing fiber inputs convey information from the vertical semicircular canals and otoliths but not the horizontal semicircular canals; 3) CFRs evoked in a particular sagittal zone do not influence SSs in adjacent zones; 4) modulation of a CFRs in a particular Purkinje cell can occur without modulation of SSs in the same Purkinje cell, although modulation of SSs was not observed in the absence of CFR modulation; and 5) modulation of SSs sometimes preceded that of CFRs in the same cell, implying that interneuronal pathways may contribute to SS modulation. Climbing fiber-driven Golgi cells, the inhibitory axon terminals of which end on granule cell dendrites in the classic glomerular synapse, may provide this interneuronal mechanism.

Dynamics of squirrel monkey linear vestibuloocular reflex and interactions with fixation distance.

Horizontal, vertical, and torsional eye movements were recorded using the magnetic search-coil technique during linear accelerations along the interaural (IA) and dorsoventral (DV) head axes. Four squirrel monkeys were translated sinusoidally over a range of frequencies (0.5-4.0 Hz) and amplitudes (0.1-0.7 g peak acceleration). The linear vestibuloocular reflex (LVOR) was recorded in darkness after brief presentations of visual targets at various distances from the subject. With subjects positioned upright or nose-up relative to gravity, IA translations generated conjugate horizontal (IA horizontal) eye movements, whereas DV translations with the head nose-up or right-side down generated conjugate vertical (DV vertical) responses. Both were compensatory for linear head motion and are thus translational LVOR responses. In concert with geometric requirements, both IA-horizontal and DV-vertical response sensitivities (in deg eye rotation/cm head translation) were related linearly to reciprocal fixation distance as measured by vergence (in m-1, or meter-angles, MA). The relationship was characterized by linear regressions, yielding sensitivity slopes (in deg.cm-1.MA-1) and intercepts (sensitivity at 0 vergence). Sensitivity slopes were greatest at 4.0 Hz, but were only slightly more than half the ideal required to maintain fixation. Slopes declined with decreasing frequency, becoming negligible at 0.5 Hz. Small responses were observed when vergence was zero (intercept), although no response is required. Like sensitivity slope, the intercept was largest at 4.0 Hz and declined with decreasing frequency. Phase lead was near zero (compensatory) at 4.0 Hz, but increased as frequency declined. Changes in head orientation, motion axis (IA vs. DV), and acceleration amplitude produced slight and sporadic changes in LVOR parameters. Translational LVOR response characteristics are consistent with high-pass filtering within LVOR pathways. Along with horizontal eye movements, IA translation generated small torsional responses. In contrast to the translational LVORs, IA-torsional responses were not systematically modulated by vergence angle. The IA-torsional LVOR is not compensatory for translation because it cannot maintain image stability. Rather, it likely compensates for the effective head tilt simulated by translation. When analyzed in terms of effective head tilt, torsional responses were greatest at the lowest frequency and declined as frequency increased, consistent with low-pass filtering of otolith input. It is unlikely that IA-torsional responses compensate for actual head tilt, however, because they were similar for both upright and nose-up head orientations. The IA-torsional and -horizontal LVORs seem to respond only to linear acceleration along the IA head axis, and the DV-vertical LVOR to acceleration along the head's DV axis, regardless of gravity.

Galvanic vestibular stimulation in humans: effects on otolith function in roll

The effects of unilateral galvanic vestibular stimulation on (1) ocular torsion, (2) subjective tilt of the peripheral visual field, and (3) subjective tilt of a foveal vertical line were measured in 12 healthy subjects. A rectangular, unipolar binaural electric current was applied to the subject's mastoid. Anodal stimulation of the right mastoid led to an ipsiversive tonic ocular torsion (0.5–3.7°) and to a contralateral tilt of both the peripheral visual field (1–9°), and a foveal vertical line (0.5–6.2°). There was a correlation between the amount of the three measured parameters and the strength of the applied current. Static ocular torsion, central and peripheral visual tilts represent stimulus-induced tonic otolith imbalance between the two labyrinths. Thus, galvanic vestibular stimulation not only affects dynamic semicircular canal input but also static otolith input in the roll plane.

Evaluating otolith function with subjective visual vertical discrimination

This report summarizes our experiences with the subjective visual vertical (SVV) as a clinical neuro-otological tool. In the SVV test, patients have to orient a dim light bar in an otherwise dark surrounding earth-vertical, using a remote-control. Normal subjects in an upright position did not deviate more than 2 degrees from true vertical. After vestibular neurectomy, the SVV was consistently tilted by some 12 degrees toward the affected ear. Smaller tilts (approximately 7 degrees) of the SVV occurred in patients with spontaneous peripheral vestibular diseases. This shift in SVV disappeared within weeks to months, similar to the spontaneous nystagmus. After stapes surgery slight deviations of the SVV towards the unoperated ear were seen in about 20% of the patients, indicating a slight irritation of the otolith organs. Assessed in an upright position, the SVV thus may be regarded as reflecting tonic otolithic input differences between the two ears. Asymmetries in the shifts of the SVV induced by roll tilts of the gravito-inertial vector by eccentric rotations of the subject have been proposed as a test for otolithic sensitivity. In our studies such asymmetries in the shifts of the SVV could not be induced by 26 degrees or 90 degrees roll tilts of subjects towards the affected or healthy ears. A simple clinical test to reveal unilateral otolithic sensitivity (comparable to an otolithic "caloric test") thus still has to be found.

Difference in Quick Phases Induced by Horizontal and Vertical Vestibular Stimulations: Role of the Otolithic Input

Quick phases (QPs) induced by horizontal and vertical sinusoidal vestibular stimulations were studied in rabbits, cats, and humans. In all the animals, large and frequent horizontal QPs were observed following yaw stimulation in prone position. By contrast, QPs were almost absent during roll stimulation in rabbits, and they were small and oblique during pitch stimulation in cats and humans. As a result of these differences, the range of gaze displacement induced by vestibular stimulations was greater in the horizontal plane than in the vertical one. We also found that the trajectory of the QPs in rabbits was kept horizontal even when the yaw rotation was off vertical axis of +/- 45 degrees in the sagittal plane. Moreover, in the rabbit, the rare horizontal QPs induced by roll stimulation did not change their orientation at various pitch angles of roll stimulation axis. The QPs were also analyzed following roll stimulation of the rabbit in supine position. In this condition, in which the otolithic receptors were activated in the opposite way compared to prone position, large vertical QPs were elicited. We concluded that these results provide evidence that the otolithic signal plays a role in controlling occurrence and trajectory orientation of the QPs.

The coding of head orientations in neurons of bilateral vestibular nuclei of cats after unilateral labyrinthectomy: response to off-vertical axis rotation.

In decerebrate cats that had been acutely hemilabyrinthectomized (HL), the extracellular activities of vestibular nuclear neurons on the lesioned and labyrinth-intact sides were studied during constant-velocity off-vertical axis rotations (OVAR) in the clockwise (CW) and counterclockwise (CCW) directions (at 10 degrees tilt). Over the range of 1.75-15 degrees/s, two types of neuronal responses were identified on both sides. Some neurons showed symmetric and velocity-stable bidirectional response sensitivity (delta defined as the CW gain over the CCW gain) while other neurons exhibited asymmetric and velocity-variable delta. The mathematically derived gain tuning ratios of these two groups of neurons were within the range of one-dimensional and two-dimensional neurons respectively. The best response orientations in one-dimensional neurons and the orientations of the maximum response vector, S(max), in two-dimensional neurons were found to point in all directions on the horizontal plane. On the labyrinth-intact side, both the one-dimensional and two-dimensional neurons showed asymmetry in the neuron numbers and/or the response gains between the two roll quadrants as well as between the two pitch quadrants. In addition, both the neuron number and gain were significantly higher for neurons in the head-down/ipsilateral-side-down half-circle than those in the head-up/contralateral-side-down half-circle. None of the aforementioned asymmetries was observed on the lesioned side. That a comparable pattern of distribution was observed in the one-dimensional and two-dimensional neurons suggests that these neurons maintain a common spatial reference frame in encoding head orientational signals arising from the ipsilateral and contralateral otoliths. Furthermore, a predominance of two-dimensional neurons that exhibited a greater gain with CW rotations was observed on both sides of HL cats. Of the response dynamics observed amongst neurons on the two sides of HL cats, no difference was found with regard to the response gain and the pattern of response lead. However, a difference in response lag was observed between neurons on the two sides of HL cats. These suggest that there is a segregation of otolithic signals to reach the ipsilateral and contralateral vestibular nuclei. Taken together, the present study demonstrates that one-dimensional and two-dimensional neuronal responses could be elicited with inputs arising solely from the ipsilateral or contralateral otoliths. The observed orientational tuning and the CW-CCW asymmetry to bidirectional rotation may provide the essential directional coding of head orientations. Further, the imbalance of spatial/dynamic response patterns between the bilateral vestibular nuclei following the restriction of otolith inputs by HL implies that converging otolithic inputs from the bilateral labyrinths are essential for producing the neuronal responses in control animals. The results are also discussed in terms of the possible contribution of the various neural asymmetries between neuronal subpopulations in the bilateral vestibular nuclei to the behavioral symptoms accompanying acute HL.

The human horizontal vestibulo-ocular reflex during combined linear and angular acceleration.

We employed binocular magnetic search coils to study the vestibulo-ocular reflex (VOR) and visually enhanced vestibulo-ocular reflex (VVOR) of 15 human subjects undergoing passive, whole-body rotations about a vertical (yaw) axis delivered as a series of pseudorandom transients and sinusoidal oscillations at frequencies from 0.8 to 2.0 Hz. Rotations were about a series of five axes ranging from 20 cm posterior to the eyes to 10 cm anterior to the eyes. Subjects were asked to regard visible or remembered targets 10 cm, 25 cm, and 600 cm distant from the right eye. During sinusoidal rotations, the gain and phase of the VOR and VVOR were found to be highly dependent on target distance and eccentricity of the rotational axis. For axes midway between or anterior to the eyes, sinusoidal gain decreased progressively with increasing target proximity, while, for axes posterior to the otolith organs, gain increased progressively with target proximity. These effects were large and highly significant. When targets were remote, rotational axis eccentricity nevertheless had a small but significant effect on sinusoidal gain. For sinusoidal rotational axes midway between or anterior to the eyes, a phase lead was present that increased with rotational frequency, while for axes posterior to the otolith organs phase lag increased with rotational frequency. Transient trials were analyzed during the first 25 ms and from 25 to 80 ms after the onset of the head rotation. During the initial 25 ms of transient head rotations, VOR and VVOR gains were not significantly influenced by rotational eccentricity or target distance. Later in the transient responses, 25-80 ms from movement onset, both target distance and eccentricity significantly influenced gain in a manner similar to the behavior during sinusoidal rotation. Vergence angle generally remained near the theoretically ideal value during illuminated test conditions (VVOR), while in darkness vergence often varied modestly from the ideal value. Regression analysis of instantaneous VOR gain as a function of vergence demonstrated only a weak correlation, indicating that instantaneous gain is not likely to be directly dependent on vergence. A model was proposed in which linear acceleration as sensed by the otoliths is scaled by target distance and summed with angular acceleration as sensed by the semicircular canals to control eye movements. The model was fit to the sinusoidal VOR data collected in darkness and was found to describe the major trends observed in the data. The results of the model suggest that a linear interaction exists between the canal and otolithic inputs to the VOR.

Responses of neurons of the cat central cervical nucleus to natural neck and vestibular stimulation.

1. The central cervical nucleus (CCN) is known to receive neck and vestibular input and to project to the contralateral cerebellum and vestibular nuclei. To investigate the processing of neck and vestibular input by cells in the CCN, we studied their responses to sinusoidal neck rotation and to whole-body tilt in vertical planes in decerebrate, paralyzed cats. CCN neurons were identified by antidromic stimulation with electrodes placed in or near the contralateral restiform body. 2. For every neuron, we first identified the preferred direction of neck rotation (response vector orientation), then studied the neuron's dynamics with rotations in a plane close to this direction at 0.05-1 Hz. 3. Responses of CCN neurons to neck rotation resembled those of previously studied neck spindle primary afferents in terms of their dynamics and nonlinear responses to stimuli of differing amplitudes. They also resembled the neck responses of Deiters' neurons studied in similar preparations. 4. The activity of two-thirds of CCN neurons also was modulated by natural vestibular stimulation. Orientation and dynamics of vestibular responses were characterized in the same way as neck responses. Labyrinthine input originated predominantly from the contralateral vertical canals, and there was no evidence of otolith input. Neck and vestibular inputs were always antagonistic, but the gain of the vestibular response was lower than that of the neck response at all frequencies studied. 5. The quantitative aspects of the interaction between neck and vestibular inputs can be expected to vary with the type of preparation and with stimulus parameters, and its functional significance remains to be investigated.

Behavior of Cells Without Eye Movement Sensitivity in the Vestibular Nuclei During Combined Rotational and Translational Stimuli

A total of 74 neurons that lacked eye movement sensitivity were recorded within the confines of the rostral medial and medial lateral vestibular nuclei. Of these, 36 had response characteristics that were consistent with combined canal and otolith inputs (CAOT neurons), 18 received canal inputs only (CA neurons), and 20 had otolith inputs only (OT neurons). Responses were measured during both rotational and combined rotational and translational stimuli at 0.5 and 3.0 Hz. The otolith signal was found to lag acceleration markedly at both frequencies. Indeed, one subset of CAOT neurons had otolith responses that led translational velocity by only 12 degrees at 0.5 Hz. All translation-responsive neurons decreased their phase lag with respect to acceleration when the stimulus frequency was increased and exhibited a large increase in sensitivity. As these cells have response dynamics that lie between those seen in otolith afferents and those required to drive the motoneurons during the translational VOR, they may represent an intermediate stage in the signal processing.

Can a unilateral loss of otolithic function be clinically detected by assessment of the subjective visual vertical?

Asymmetries in the settings of the subjective visual vertical after unilateral vestibular neurectomy during eccentric centrifugation [3] might provide a clinical test for unilateral otolithic function. This study investigates whether these asymmetries can also be revealed by a technically much easier practicable roll tilt of the subject relative to gravity instead of a roll tilt of the gravitational force on a human centrifuge. Twenty-seven normal subjects and 13 patients before surgery indicated verticality very accurately in the upright position. In 26° roll positions (subjects seated on a slanted chair), they were only slightly more variable with no asymmetries larger than 5.3 and 7.8° in normals and preoperative patients, respectively, between the roll positions toward the healthy and toward the affected ear. One week after surgical unilateral vestibular deafferentation, there was a consistent shift (mean 11.9°) of the subjective vertical toward the affected ear in all patients and in all body positions. When the settings in the two roll tilt positions were referred to the setting in upright position, the group means of the patients were symmetrical although single subjects revealed asymmetries up to 22.4°. Only one of four patients who were tested also during eccentric rotation revealed an important asymmetry with decreased sensitivity for tilts of the gravitational vector toward the affected ear. Measuring the subjective visual vertical assesses only asymmetrical tonic otolithic input, while a simple clinical test for unilateral otolithic sensitivity still has to be found.

Vestibular and visual climbing fiber signals evoked in the uvula-nodulus of the rabbit cerebellum by natural stimulation.

1. The cerebellar uvula-nodulus receives vestibular projections from primary and secondary vestibular afferents as well as vestibularly related climbing fibers. It also receives visually related information from climbing fiber pathways. In this experiment we investigated how this information is mapped onto the uvula-nodulus. We studied the specificity, dynamics, and topographic distribution of climbing fiber responses (CFRs), simple spike responses, and mossy fiber terminal responses evoked by vestibular and optokinetic stimulation in rabbits anesthetized with alpha-chloralose. 2. Vestibularly evoked CFRs were found in the ventral uvula and nodulus. These responses were evoked during static roll tilt of the rabbit about a longitudinal axis and by sinusoidal oscillation about the longitudinal axis. Purely static responses were attributed to stimulation of the utricular otolith by the linear acceleration of gravity. CFRs that lacked a static component were attributed to activation of the semicircular canals. 3. Using a "null technique" we showed that the canal-sensitive CFRs were caused by stimulation of the anterior or posterior semicircular canals. Of the CFRs classified as canal related, 96% could be attributed to stimulation of the vertical semicircular canals. 4. Increases in CFRs were correlated with decreases in simple spike responses in half the Purkinje cells from which we recorded. These climbing-fiber-induced pauses in simple spikes occurred during spontaneous climbing fiber discharge as well as during climbing fiber discharge evoked by vestibular stimulation. The duration of this pause was inversely proportional to the spontaneous level of simple spikes before the occurrence of a CFR. In the other half of the recorded population of Purkinje cells, vestibularly driven CFRs did not alter the simple spike responses. 5. Vestibularly and visually mediated CFRs were topographically represented on the surface of the uvula-nodulus. CFRs driven by ipsilateral otolithic inputs were distributed over the entire mediolateral surface of the uvula-nodulus. CFRs driven by the ipsilateral posterior semicircular canal were distributed in a sagittal strip approximately 1.5 mm wide, extending laterally from the midline of the nodulus. CFRs driven exclusively by horizontal, posterior-->anterior optokinetic stimulation of the ipsilateral eye were distributed in a sagittal strip approximately 0.5 mm wide located 0.5-1.0 mm from the midline and restricted to the ventral nodulus. CFRs driven by the ipsilateral anterior semicircular canal were found in a sagittal strip approximately 1.0 mm wide extending 1.0-2.0 mm from the midline. 6. The sagittal, topographically arrayed climbing fiber strips effectively map a mediolateral gradient of possible postural responses based on vestibular and optokinetic information.

Horizontal optokinetic nystagmus in the pigeon during static tilts in the frontal plane.

The influence of lateral static tilts of the body (30 degrees, 45 degrees) on horizontal optokinetic nystagmus induced by rotation of an optokinetic cylinder at a constant rate (16 degrees, 30 degrees/sec) was investigated in 16 pigeons. The experiments made it possible to identify a statistically significant tilt-dependent asymmetry of the tonic otolithic influences on the optokinetic system which consisted in a marked inhibitory effect on horizontal optokinetic nystagmus of right-sided tilts by contrast with left-sided. The separate recording of oculomotor responses of the right and left eyes showed that the temporonasal-nasotemporal (TN-NT) asymmetry of horizontal optokinetic nystagmus which exists in the norm in the pigeon is maintained under the conditions of stationary lateral tilts of the body for the eye which is in the upper position, and is replaced by a symmetrical pattern for the eye which is in the lower position. The results make it possible to hold the view that the mechanism of TN-NT asymmetry is controlled by otolithic inputs, and that its function may be substantially modified under the influence of the reorientation of the otolithic membranes in the gravitational field.

Vestibulo-ocular reflex

Recent animal and clinical studies on the vestibulo-ocular reflex deal with a number of physiological and clinical aspects from which three were chosen for this review: (1) the torsional vestibulo-ocular reflex and its disorders; (2) the otolith contribution to the vestibulo-ocular reflex; and (3) neurotransmitters, neuropharmacological aspects, and medical treatment. Disorders of the vestibulo-ocular reflex can be classified according to the three major planes of action, yaw plane, pitch plane, and roll plane, which equate with horizontal nystagmus, upbeat or downbeat nystagmus, and torsional nystagmus, respectively. The particular interest in the torsional vestibulo-ocular reflex arises from new methods for measuring ocular torsion, especially the three-dimensional eye-movement recordings with scleral coils. These methods make it possible to do three-dimensional analysis of the differential effects of horizontal and vertical semicircular canal function and their individual disorders of the torsional vestibulo-ocular reflex. Otolith and semicircular canal inputs converge at the level of the vestibular nuclei to subserve static graviceptive and dynamic torsional and pitch function. The elaboration of the particular sensorial weight of the input from either the otoliths or the semicircular canal is currently a challenge for both physiologists and neurologists. Disorders of otolith function, still absent from the diagnostic repertoire of most neurologists, are increasingly being reported. The most promising developments in therapeutic measures may come from research on vestibular neurotransmitters, their agonists and antagonists. A number of pharmacological agents are effective suppressants of pathological eye movements. However, systematic prospective studies are needed.(ABSTRACT TRUNCATED AT 250 WORDS)

Reorientation of Poststimulus Nystagmus in Tilted Humans1

Recent studies indicate that the direction of postrotatory nystagmus and optokinetic afternystagmus reorients toward earth-horizontal in tilted subjects. To further examine this phenomenon in humans, we studied 8 adults (4M, 4F) with no history of neurologic or otologic disease. Vestibular stimulation consisted of yaw off-vertical axis rotation (OVAR) trapezoids with eyes open in the dark at 60 degrees/s constant velocity with a tilt angle of 30 degrees and a deceleration at 100 degrees/s2 to a stop in either the right-ear-down or the left-ear-down position. The optokinetic stimulus consisted of 5 degrees wide black and white stripes projected against a cylindrical visual surround 1 m in diameter rotated at a constant velocity of 30 degrees/s. The projector, visual surround, and subject were all tilted by 30 degrees; subjects were placed either in the right-ear-down or left-ear-down position. Eye position was measured using the magnetic scleral search coil technique. Each trial was scrutinized for the presence of reorientation of nystagmus in the subject's roll plane by looking for vertical nystagmus in the appropriate direction. Results indicated that reorientation of postrotatory nystagmus following OVAR was variable but often present. Reorientation of optokinetic afternystagmus was neither as consistent nor as robust as that seen following OVAR. These findings confirm that humans exhibit a predilection for eye rotations in the earth-horizontal plane.(ABSTRACT TRUNCATED AT 250 WORDS)

Rotational kinematics of the human vestibuloocular reflex. I. Gain matrices

1. This series of three papers aims to describe the three-dimensional, kinematic input-output relations of the rotational vestibuloocular reflex (VOR) in humans, and to identify the functional advantages of these relations. In this first paper the response to sinusoidal rotation in darkness at 0.3 Hz, maximum speed 37.5%/s, was quantified by the use of the three-dimensional analogue of VOR gain: a 3 x 3 matrix where each element describes the dependence of one component (torsional, vertical, or horizontal) of eye velocity on one component of head velocity. 2. The three matrix elements indicating collinear gains (i.e., dependence of torsional eye velocity on torsional head velocity, vertical on vertical, and horizontal on horizontal) were smaller than the -1's required for optimal retinal image stabilization. Of these three the torsional gain was weakest: -0.37 for rotation about an earth-vertical axis, versus -0.73 and -0.64 for vertical and horizontal gains. Matrix elements indicating cross talk were mostly negligible. There was a tendency to leftward eye rotation in response to clockwise head motion, but this was not statistically significant. 3. VOR responses were compared for rotation about earth-vertical and earth-horizontal axes. The varying otolith input due to the rotation of the gravity vector relative to the head during earth-horizontal axis rotation made no difference to the collinear gains. 4. There were no consistent phase leads or lags except for a torsional phase lead of up to 10 degrees, usually more marked for clock-wise head rotation versus counterclockwise, and for oblique axis rotations versus purely torsional. 5. Torsional gain was magnified, averaging -0.52, when the torsional component of head rotation was only a small part of a predominantly vertical or horizontal rotation, i.e., when the axis of head rotation was near the frontal plane. Because most natural head rotations occur about such axes, the torsional VOR is probably somewhat stronger than the response to pure torsion would suggest. 6. The speed of eye rotation in response to a given stimulus varied widely among subjects, but the direction of rotation was much more uniform. For head rotations about oblique axes out of the frontal plane, there was a systematic misalignment of eye and head axes, with eye axes tilted toward the frontal plane. These findings can be explained on the basis of a strategy where the VOR balances the muscular effort of rotating the eyes against the cost of retinal slip.