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Noninvasive electrical stimulation of the vestibular system in humans has become an increasingly popular tool with a broad range of research and clinical applications. However, common assumptions regarding the neural mechanisms that underlie the activation of central vestibular pathways through such stimulation, known as galvanic vestibular stimulation (GVS), have not been directly tested. Here, we show that GVS is encoded by VIIIth nerve vestibular afferents with nonlinear dynamics that differ markedly from those predicted by current models. GVS produced asymmetric activation of both semicircular canal and otolith afferents to the onset versus offset and cathode versus anode of applied current, that in turn produced asymmetric eye movement responses in three awake-behaving male monkeys. Additionally, using computational methods, we demonstrate that the experimentally observed nonlinear neural response dynamics lead to an unexpected directional bias in the net population response when the information from both vestibular nerves is centrally integrated. Together our findings reveal the neural basis by which GVS activates the vestibular system, establish that neural response dynamics differ markedly from current predictions, and advance our mechanistic understanding of how asymmetric activation of the peripheral vestibular system alters vestibular function. We suggest that such nonlinear encoding is a general feature of neural processing that will be common across different noninvasive electrical stimulation approaches. SIGNIFICANCE STATEMENT Here, we show that the application of noninvasive electrical currents to the vestibular system (GVS) induces more complex responses than commonly assumed. We recorded vestibular afferent activity in macaque monkeys exposed to GVS using a setup analogous to human studies. GVS evoked notable asymmetries in irregular afferent responses to cathodal versus anodal currents. We developed a nonlinear model explaining these GVS-evoked afferent responses. Our model predicts that GVS induces directional biases in centrally integrated head motion signals and establishes electrical stimuli that recreate physiologically plausible sensations of motion. Altogether, our findings provide new insights into how GVS activates the vestibular system, which will be vital to advancing new clinical and biomedical applications., (Copyright © 2023 the authors.)

From animal experiments by Cohen and Suzuki et al. in the 1960s to the first-in-human clinical trials now in progress, prosthetic electrical stimulation targeting semicircular canal branches of the vestibular nerve has proven effective at driving directionally appropriate vestibulo-ocular reflex eye movements, postural responses, and perception. That work was considerably facilitated by the fact that all hair cells and primary afferent neurons in each canal have the same directional sensitivity to head rotation, the three canals' ampullary nerves are geometrically distinct from one another, and electrically evoked three-dimensional (3D) canal-ocular reflex responses approximate a simple vector sum of linearly independent components representing relative excitation of each of the three canals. In contrast, selective prosthetic stimulation of the utricle and saccule has been difficult to achieve, because hair cells and afferents with many different directional sensitivities are densely packed in those endorgans and the relationship between 3D otolith-ocular reflex responses and the natural and/or prosthetic stimuli that elicit them is more complex. As a result, controversy exists regarding whether selective, controllable stimulation of electrically evoked otolith-ocular reflexes (eeOOR) is possible. Using micromachined, planar arrays of electrodes implanted in the labyrinth, we quantified 3D, binocular eeOOR responses to prosthetic electrical stimulation targeting the utricle, saccule, and semicircular canals of alert chinchillas. Stimuli delivered via near-bipolar electrode pairs near the maculae elicited sustained ocular countertilt responses that grew reliably with pulse rate and pulse amplitude, varied in direction according to which stimulating electrode was employed, and exhibited temporal dynamics consistent with responses expected for isolated macular stimulation. NEW & NOTEWORTHY As the second in a pair of papers on Binocular 3D Otolith-Ocular Reflexes, this paper describes new planar electrode arrays and vestibular prosthesis architecture designed to target the three semicircular canals and the utricle and saccule. With this technological advancement, electrically evoked otolith-ocular reflexes due to stimulation via utricle- and saccule-targeted electrodes were recorded in chinchillas. Results demonstrate advances toward achieving selective stimulation of the utricle and saccule.

Key Points: Considerable debate exists regarding whether electrical vestibular stimuli encoded by vestibular afferents induce a net signal of linear acceleration, rotation or a combination of the two. This debate exists because an isolated signal of head rotation encoded by the vestibular afferents can cause perceptions of both linear and angular motion. We recorded participants' perceptions in different orientations relative to gravity and predicted their responses by modelling the effect of electrical vestibular stimuli on vestibular afferents and a current model of central vestibular processing. We show that, even if electrical vestibular stimuli are encoded as a net signal of head rotation, participants perceive both linear acceleration and rotation motions, provided the electrical stimulation-induced rotational vector has a component orthogonal to gravity. The emergence of a perception of linear acceleration from a single rotational input signal clarifies the origins of the neural mechanisms underlying electrical vestibular stimulation., Abstract: Electrical vestibular stimulation (EVS) is an increasingly popular biomedical tool for generating sensations of virtual motion in humans, for which the mechanism of action is a topic of considerable debate. Contention surrounds whether the evoked vestibular afferent activity encodes a signal of net rotation and/or linear acceleration. Central processing of vestibular self-motion signals occurs through an internal representation of gravity that can lead to inferred linear accelerations in absence of a true inertial acceleration. Applying this model to virtual signals of rotation evoked by EVS, we predict that EVS will induce behaviours attributed to both angular and linear motion, depending on the head orientation relative to gravity. To demonstrate this, 18 subjects indicated their perceived motion during sinusoidal EVS when in one of four head/body positions orienting the gravitational vector parallel or orthogonal to the EVS rotation vector. During stimulation, participants selected one simulated movement from seven that corresponded best to what they perceived. Participants' responses in each orientation were predicted by a model combining the influence of EVS on vestibular afferents with known mechanisms of vestibular processing. When the EVS rotation vector had a component orthogonal to gravity, human perceptual responses were consistent with a non-zero central estimate of interaural or superior-inferior linear acceleration. The emergence of a perception of linear acceleration from a single rotational input signal clarifies the origins of the neural mechanisms underlying EVS, which has important implications for its use in human biomedical or sensory augmentation applications., (© 2019 The Authors. The Journal of Physiology © 2019 The Physiological Society.)

Human subjects placed in strong magnetic fields such as in an MRI scanner often feel dizzy or vertiginous. Recent studies in humans and animals have shown that these effects arise from stimulation of the labyrinth and are accompanied by nystagmus. Here, we measured the three-dimensional pattern of nystagmus using video eye tracking in five normal human subjects placed in a 7T MRI to infer which semicircular canals are activated by magnetic vestibular stimulation. We found that the nystagmus usually had a torsional as well as a horizontal component. Analysis of the relative velocities of the three eye movement components revealed that the lateral and anterior (superior) canals are the only canals activated, and by a similar amount.

During head/body movements, gaze stability is ensured by transformation of motion-related sensory signals into respective motor commands. Passively induced motion in all vertebrates including amphibians evokes a robust vestibulo-ocular reflex, suggesting an equally important role of this motor reaction during actively induced motion. However, during self-induced movements including locomotion, motor efference copies offer a convenient additional substrate for counteracting retinal image displacements. During such locomotor activity in Xenopus laevis tadpoles, spinal central pattern generator-derived efference copies elicit spatio-temporally specific eye movements, which are functionally appropriate to offset swimming-related retinal image displacements. In addition, passively induced horizontal semicircular canal signals are suppressed, making intrinsic spino-extraocular motor coupling the dominating mechanism for gaze stabilization during locomotion. The presence of functionally appropriate efference copy-driven eye movements in adult frogs with limb-based locomotion suggests that this mechanism might play a role for gaze stability during rhythmic locomotion also in other vertebrates.

Vestibulo-ocular reflexes (VOR) ensure gaze stability during locomotion and passively induced head/body movements. In precocial vertebrates such as amphibians, vestibular reflexes are required very early at the onset of locomotor activity. While the formation of inner ears and the assembly of sensory-motor pathways is largely completed soon after hatching, angular and translational/tilt VOR display differential functional onsets and mature with different time courses. Otolith-derived eye movements appear immediately after hatching, whereas the appearance and progressive amelioration of semicircular canal-evoked eye movements is delayed and dependent on the acquisition of sufficiently large semicircular canal diameters. Moreover, semicircular canal functionality is also required to tune the initially omnidirectional otolith-derived VOR. The tuning is due to a reinforcement of those vestibulo-ocular connections that are co-activated by semicircular canal and otolith inputs during natural head/body motion. This suggests that molecular mechanisms initially guide the basic ontogenetic wiring, whereas semicircular canal-dependent activity is required to establish the spatio-temporal specificity of the reflex. While a robust VOR is activated during passive head/body movements, locomotor efference copies provide the major source for compensatory eye movements during tail- and limb-based swimming of larval and adult frogs. The integration of active/passive motion-related signals for gaze stabilization occurs in central vestibular neurons that are arranged as segmentally iterated functional groups along rhombomere 1-8. However, at variance with the topographic maps of most other sensory systems, the sensory-motor transformation of motion-related signals occurs in segmentally specific neuronal groups defined by the extraocular motor output targets.

Background: The observation or measurement of eye movement can aid in the detection and localization of vestibular pathology due to the relationship between the function of the vestibular sensory receptors in the inner ear and the eye movements produced by the vestibulo-ocular reflex (VOR). The majority of bedside and laboratory tests of vestibular function involve the observation or measurement of horizontal eye movements (i.e., horizontal VOR) produced by stimuli that activate the horizontal semicircular canals (SCCs) and the superior vestibular nerve. The video head impulse test (vHIT) is a new clinical test of dynamic SCC function that uses a high-speed digital video camera to record head and eye movement during and immediately after passive head rotations. The SYNAPSYS Inc. vHIT device measures the "canal deficit" (deviation in gaze) during passive head impulses in the horizontal and diagonal (vertical) planes. There is, however, a paucity of data that has been reported using this device., Purpose: The purpose of this study was to obtain normative data and assess the test-retest reliability of the SYNAPSYS vHIT (version 2.0)., Research Design: A prospective repeated measures design was utilized., Study Sample: Thirty young adults with normal hearing, normal caloric test results, and a negative history of vestibular disorder, neurological disease, open or closed head injury, or cervical spine injury participated in the study., Data Collection and Analysis: A single examiner manually rotated each participant's head in the horizontal and diagonal planes in two directions (left and right in the horizontal plane; downward and upward in each diagonal plane) resulting in the stimulation of each of the six SCCs. Each participant returned for repeat testing to assess test-retest reliability. The effects of ear, session, and semicircular canal (horizontal, anterior, posterior) on the magnitude of canal deficit during the vHIT were assessed using repeated measures analysis of variance., Results: The mean canal deficit of the horizontal canals (8.3%) was significantly lower than the mean canal deficit of the anterior canals (16.5%) and the posterior canals (15.2%); there was no significant difference between the mean canal deficits of the anterior and posterior canals. The main effects of session and ear on canal deficit were not significant, and there were no significant interaction effects. There was no significant difference between the mean canal deficit for session 1 and session 2 for the horizontal, anterior, and posterior canals. The 95th percentiles for canal deficit were 19, 26, and 22% for the horizontal, anterior, and posterior SCCs, respectively., Conclusions: Testing of all six SCCs was completed in most participants in ∼10 min and was well-tolerated. The vHIT has some important advantages relative to more established laboratory tests of horizontal SCC function including the ability to assess the vertical SCCs, lower cost, shorter test time, greater portability, minimal space requirements, and increased patient comfort. Additional data, however, should be obtained from older participants with normal vestibular function and from patients with vestibular disorders. Within-subject comparisons between the results of the vHIT and the caloric and rotary chair tests will be important in determining the role of the vHIT in the vestibular test battery., (American Academy of Audiology.)

To investigate the characteristics of eye movements produced by electrical stimulation of semicircular canal afferents, we studied the spatial and temporal features of eye movements elicited by short-term lateral canal stimulation in two squirrel monkeys with plugged lateral canals, with the head upright or statically tilted in the roll plane. The electrically induced vestibuloocular reflex (eVOR) evoked with the head upright decayed more quickly than the stimulation signal provided by the electrode, demonstrating an absence of the classic velocity storage effect that improves the dynamics of the low-frequency VOR. When stimulation was provided with the head tilted in roll, however, the eVOR decayed more rapidly than when the head was upright, and a cross-coupled vertical response developed that shifted the eye's rotational axis toward alignment with gravity. These results demonstrate that rotational information provided by electrical stimulation of canal afferents interacts with otolith inputs (or other graviceptive cues) in a qualitatively normal manner, a process that is thought to be mediated by the velocity storage network. The observed interaction between the eVOR and graviceptive cues is of critical importance for the development of a functionally useful vestibular prosthesis. Furthermore, the presence of gravity-dependent effects (dumping, spatial orientation) despite an absence of low-frequency augmentation of the eVOR has not been previously described in any experimental preparation.

Hypothesis: It is possible to implant a stimulating electrode array in the semicircular canals without damaging rotational sensitivity or hearing. The electrodes will evoke robust and precisely controlled eye movements., Background: A number of groups are attempting to develop a neural prosthesis to ameliorate abnormal vestibular function. Animal studies demonstrate that electrodes near the canal ampullae can produce electrically evoked eye movements. The target condition of these studies is typically bilateral vestibular hypofunction. Such a device could potentially be more widely useful clinically and would have a simpler roadmap to regulatory approval if it produced minimal or no damage to the native vestibular and auditory systems., Methods: An electrode array was designed for insertion into the bony semicircular canal adjacent to the membranous canal. It was designed to be sufficiently narrow so as to not compress the membranous canal. The arrays were manufactured by Cochlear, Ltd., and linked to a Nucleus Freedom receiver/stimulator. Seven behaviorally trained rhesus macaques had arrays placed in 2 semicircular canals using a transmastoid approach and "soft surgical" procedures borrowed from Hybrid cochlear implant surgery. Postoperative vestibulo-ocular reflex was measured in a rotary chair. Click-evoked auditory brainstem responses were also measured in the 7 animals using the contralateral ear as a control., Results: All animals had minimal postoperative vestibular signs and were eating within hours of surgery. Of 6 animals tested, all had normal postoperative sinusoidal gain. Of 7 animals, 6 had symmetric postoperative velocity step responses toward and away from the implanted ear. The 1 animal with significantly asymmetric velocity step responses also had a significant sensorineural hearing loss. One control animal that underwent canal plugging had substantial loss of the velocity step response toward the canal-plugged ear. In 5 animals, intraoperative electrically evoked vestibular compound action potential recordings facilitated electrode placement. Postoperatively, electrically evoked eye movements were obtained from electrodes associated with an electrically evoked vestibular compound action potential wave form. Hearing was largely preserved in 6 animals and lost in 1 animal., Conclusion: It is possible to implant the vestibular system with prosthetic stimulating electrodes without loss of rotational sensitivity or hearing. Because electrically evoked eye movements can be reliably obtained with the assistance of intraoperative electrophysiology, it is appropriate to consider treatment of a variety of vestibular disorders using prosthetic electrical stimulation. Based on these findings, and others, a feasibility study for the treatment of human subjects with disabling Ménière's disease has begun.

Vertigo in and around magnetic resonance imaging (MRI) machines has been noted for years [1, 2]. Several mechanisms have been suggested to explain these sensations [3, 4], yet without direct, objective measures, the cause is unknown. We found that all of our healthy human subjects developed a robust nystagmus while simply lying in the static magnetic field of an MRI machine. Patients lacking labyrinthine function did not. We use the pattern of eye movements as a measure of vestibular stimulation to show that the stimulation is static (continuous, proportional to static magnetic field strength, requiring neither head movement nor dynamic change in magnetic field strength) and directional (sensitive to magnetic field polarity and head orientation). Our calculations and geometric model suggest that magnetic vestibular stimulation (MVS) derives from a Lorentz force resulting from interaction between the magnetic field and naturally occurring ionic currents in the labyrinthine endolymph fluid. This force pushes on the semicircular canal cupula, leading to nystagmus. We emphasize that the unique, dual role of endolymph in the delivery of both ionic current and fluid pressure, coupled with the cupula's function as a pressure sensor, makes magnetic-field-induced nystagmus and vertigo possible. Such effects could confound functional MRI studies of brain behavior, including resting-state brain activity., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

The vestibular organs in the base of the skull provide important information about head orientation and motion in space. Previous studies have suggested that both angular velocity information from the semicircular canals and information about head orientation and translation from the otolith organs are centrally processed in an internal model of head motion, using the principles of optimal estimation. This concept has been successfully applied to model behavioral responses to classical vestibular motion paradigms. This study measured the dynamic of the vestibuloocular reflex during postrotatory tilt, tilt during the optokinetic afternystagmus, and off-vertical axis rotation. The influence of otolith signal on the VOR was systematically varied by using a series of tilt angles. We found that the time constants of responses varied almost identically as a function of gravity in these paradigms. We show that Bayesian modeling could predict the experimental results in an accurate and consistent manner. In contrast to other approaches, the Bayesian model also provides a plausible explanation of why these vestibulooculo motor responses occur as a consequence of an internal process of optimal motion estimation.

The angular vestibulo-ocular reflex (AVOR) normally has an increased response during vergence on a near target. Some lines of evidence suggest that different vestibular afferent classes may contribute differentially to the vergence effect. For example, lesions that selectively affect those afferents sensitive to acceleration, i.e. irregular afferents, (galvanic ablation, intratympanic gentamicin) have been found to markedly reduce the vergence-mediated modulation of the AVOR. We hypothesized that a nonspecific and incomplete reduction in the AVOR response caused by canal plugging should have minimal effect on vergence-mediated modulation of the AVOR. The AVOR response to passive head impulses in canal planes (horizontal canals, left anterior-right posterior canals, right anterior-left posterior canals) while viewing a far (124 cm) or near (15 cm) target was measured in seven human subjects before and after anterior canal (AC) plugging to treat vertigo caused by dehiscence of the AC (i.e. superior canal dehiscence). The impulses were low amplitude (approximately 20 degrees ), high velocity ( approximately 150 degrees /s), high-acceleration (approximately 3,000 degrees /s(2)) head rotations administered manually by the investigator. Binocular eye and head velocity were recorded using the scleral search coil technique. The AVOR gain was defined as inverted eye velocity divided by head velocity. Before plugging, AVOR gain for the dehiscent AC went from 0.87 +/- 0.10 for far targets to 1.04 +/- 0.13 for near targets (+19.1 +/- 7.3%). After plugging, the AC AVOR gain went from 0.50 +/- 0.10 for far targets to 0.59 +/- 0.11 for near targets (+19.7 +/- 6.1%). There was no difference in the vergence-mediated gain increase between pre- and post-plugged conditions (multi-way analysis of variance: P = 0.66). AC plugging also did not change the latency of the AVOR for either AC. We hypothesize that canal plugging, unlike gentamicin or galvanic ablation, has no effect on vergence-mediated modulation of the AVOR because plugging does not preferentially affect irregular afferents.

Controversy remains about the linearity of the interaction between horizontal semicircular canal and otolith organ vestibulo-ocular reflexes (VORs) in the generation of horizontal eye movements during head movements including both rotational and translational components. We used three eccentric rotation techniques to investigate this interaction in human subjects: (1) the tangential interaural acceleration was varied using three head positions (on-axis, 25 and 40 cm ahead of the rotational axis), while angular head velocity remained unchanged; (2) the magnitude of the angular head velocity was varied with head eccentricity to keep the tangential interaural acceleration unchanged; (3) the subject's head was oriented either upright or 90 degrees forward from upright (nose-down). Experiments were performed in complete darkness with the subjects remembering a close earth-fixed target (20 cm distant) while being rotated at 1.2 and 1.8 Hz. Our data showed that the translational component of the VOR evoked during eccentric yaw rotation increased proportionally with an increase in head eccentricity, i.e. with tangential acceleration. We also found that the translational component of the VOR was equal for motion stimuli producing identical interaural tangential accelerations even when angular velocities differed. In addition, we found that the translational component of the VOR evoked during head upright eccentric rotation was equal to the translational VOR evoked during nose-down rotation for a given stimulus and head eccentricity. We conclude that these three findings are in agreement with what would be expected from a linear interaction (i.e. algebraic summation) between otolith organ and horizontal canal VORs for the generation of horizontal compensatory eye movements during head motion.

After acute vestibular loss in humans or animals, eye-movement responses to rapid horizontal ipsilesional head rotations ("head impulses") show that there is severe, permanent impairment of the angular vestibulo-ocular reflex. The basis for this appears to be an inhibitory saturation of ipsilesional vestibular nerve, and perhaps vestibular nucleus afferents, in response to high-acceleration, off-direction stimulation of the sole functioning member of any pair of semicircular canals. For the clinician, impulsive testing is an easy and reliable way to identify severe unilateral as well as bilateral impairment of semicircular canal function.

The rotational vestibulo-ocular reflex (rVOR) contributes to gaze stabilitization by compensating head rotational movements sensed by the semicircular canals (SCC). The CNS improves the performance of the horizontal rVOR through the so called velocity storage mechanism (VSM). However the properties of the VSM in response to pitch rotations are less well known. We recorded eye movements evoked by whole-body constant-velocity pitch rotations about an earth-horizontal, interaural axis in four healthy human subjects. Subjects were tumbled forward, and backward, at 60 deg/s for over one minute using a 3D turntable. In these conditions also the otoliths contribute to the perception of head rotation because they sense the changes in direction of the gravity vector. The vertical slow phase velocity (SPV) responses show the typical exponential decay of the rVOR and a residual, otolith-driven sinusoidal modulation with a bias. Here the estimates of the contributions coming from the otoliths and from the canals are based on a linear summation hypothesis. The time constants of the canal-driven vertical component of the SPV ranged from 6 to 9 seconds. These values are closer to those produced by the SCC alone than the typical 20 s produced by the VSM in the horizontal plane, confirming the relatively small contribution of the VSM to these vertical responses. We also show that the estimation method, while it may be not physiologically accurate, is easy to implement and leads to reliable results.

Two central, related questions in motor control are 1) how the brain represents movement directions of various effectors like the eyes and head and 2) how it constrains their redundant degrees of freedom. The interstitial nucleus of Cajal (INC) integrates velocity commands from the gaze control system into position signals for three-dimensional eye and head posture. It has been shown that the right INC encodes clockwise (CW)-up and CW-down eye and head components, whereas the left INC encodes counterclockwise (CCW)-up and CCW-down components, similar to the sensitivity directions of the vertical semicircular canals. For the eyes, these canal-like coordinates align with Listing's plane (a behavioral strategy limiting torsion about the gaze axis). By analogy, we predicted that the INC also encodes head orientation in canal-like coordinates, but instead, aligned with the coordinate axes for the Fick strategy (which constrains head torsion). Unilateral stimulation (50 microA, 300 Hz, 200 ms) evoked CW head rotations from the right INC and CCW rotations from the left INC, with variable vertical components. The observed axes of head rotation were consistent with a canal-like coordinate system. Moreover, as predicted, these axes remained fixed in the head, rotating with initial head orientation like the horizontal and torsional axes of a Fick coordinate system. This suggests that the head is ordinarily constrained to zero torsion in Fick coordinates by equally activating CW/CCW populations of neurons in the right/left INC. These data support a simple mechanism for controlling head orientation through the alignment of brain stem neural coordinates with natural behavioral constraints.

Previous studies of vestibulo-ocular function in patients with anxiety disorders have suggested a higher prevalence of peripheral vestibular dysfunction compared to control populations, especially in panic disorder with agoraphobia. Also, our recent companion studies have indicated abnormalities in postural control in patients with anxiety disorders who report a high degree of space and motion discomfort. The aim of the present study was to assess the VOR, including the semicircular canal-ocular reflex, the otolith-ocular reflex, and semicircular canal-otolith interaction, in a well-defined group of patients with anxiety disorders. The study included 72 patients with anxiety disorders (age 30.6 +/- 10.6 yrs; 60 (83.3% F) and 29 psychiatrically normal controls (age 35.0 +/minus; 11.6 yrs; 24 (82.8% F). 25 patients had panic disorder; 47 patients had non-panic anxiety. Patients were further categorized based on the presence (45 of 72) or absence (27 of 72) of height phobia and the presence (27 of 72) or absence (45 of 72) of excessive space and motion discomfort (SMD). Sinusoidal and constant velocity earth-vertical axis rotation (EVAR) was used to assess the semicircular canal-ocular reflex. Constant velocity off-vertical axis rotation (OVAR) was used to assess both the otolith-ocular reflex and static semicircular canal-otolith interaction. Sinusoidal OVAR was used to assess dynamic semicircular canal-otolith interaction. The eye movement response to rotation was measured using bitemporal electro-oculography. Results showed a significantly higher VOR gain and a significantly shorter VOR time constant in anxiety patients. The effect of anxiety on VOR gain was significantly greater in patients without SMD as compared to those with SMD. Anxiety patients without height phobia had a larger OVAR modulation. We postulate that in patients with anxiety, there is increased vestibular sensitivity and impaired velocity storage. Excessive SMD and height phobia seem to have a mitigating effect on abnormal vestibular sensitivity, possibly via a down-weighting of central vestibular pathways.

Three subnuclei within the inferior olive are implicated in the control of eye movement; the dorsal cap (DC), the beta-nucleus and the dorsomedial cell column (DMCC). Each of these subnuclei can be further divided into clusters of cells that encode specific parameters of optokinetic and vestibular stimulation. DC neurons respond to optokinetic stimulation in one of three planes, corresponding to the anatomical planes of the semicircular canals. Neurons in the beta-nucleus and DMCC respond to vestibular stimulation in the planes of the vertical semicircular canals and otoliths. Each these olivary nuclei receives excitatory and inhibitory signals from pre-olivary structures. The DC receives excitatory signals from the ipsilateral nucleus of the optic tract (NOT) and inhibitory signals from the contralateral nucleus prepositus hypoglossi (NPH). The beta-nucleus and DMCC receive inhibitory signals from the ipsilateral nucleus parasolitarius (Psol) and excitatory signals from the contralateral dorsal Y group. Consequently, the olivary projection to the cerebellum, although totally crossed, still represents bilateral sensory stimulation. Inputs to the inferior olive from the NOT, NPH, Psol or Y-group discharge at frequencies of 10-100 imp/s. CFRs discharge at 1-5 imp/s; a frequency reduction of an order of magnitude. Inferior olivary projections to the contralateral cerebellum are sagittally arrayed onto multiple cerebellar folia. These arrays establish coordinate systems in the flocculus and nodulus, representing head-body movement. These climbing fiber-defined spatial coordinate systems align Purkinje cell discharge onto subjacent cerebellar and vestibular nuclei. In the oculomotor system, olivo-cerebellar circuitry enhances and modifies eye movements based on movement of the head-body in space.

A recent study on static ocular counterroll suggested the existence of residual torsion (RT): when healthy subjects repositioned their head to the upright position after sustained static tilt, eye position differed from the original ocular torsion measured prior to the static head tilt. Our experiments aimed at further characterizing this phenomenon. Using a three-dimensional motorized turntable, healthy human subjects (n = 8) were rotated quasi-statically (0.05 deg/s2, 2 deg/s velocity plateau reached after 40 s) from the upright position about the naso-occipital axis. Three full whole-body rotations were completed while subjects fixed upon a blinking laser dot straight ahead in otherwise complete darkness. Three-dimensional eye movements were recorded with modified dual search coils (wires exiting inferiorly). Torsional position of the right eye at consecutive upright body positions was analyzed. The torsional eye position before the beginning of the chair rotation was defined as zero torsion. On average, the right eye was intorted by 1.3 degrees or extorted by 2.0 degrees after the first full chair rotation in the clockwise or counterclockwise direction, respectively. These torsional offset values of the right eye did not significantly change after the two subsequent full chair rotations. We conclude that RT observed after static ocular counterroll is the result of static hysteresis, that is, a position lag of the eye, which depends on the direction of head roll. The fact that residual torsion did not further increase after the first rotation cycle emphasizes that RT is a static rather than a dynamic phenomenon.

A decreasing drift of the counter-rolled eye position (OCR) during head tilt was recently described. The underlying mechanism is not known. OCR in eleven healthy subjects was recorded (Search coil, Skalar) during a head tilt paradigm in two test conditions. The head was tilted with a velocity below (test 1) and above (test 2) detection threshold for the semicircular canals (SC) and held static for eight minutes. A significant drift of OCR was revealed in test 2 (P = .0006, ANOVA) and close to significant in test 1 (P = .07). No statistical difference was found between the two test conditions. The results suggest that the OCR drift was not caused by the SC complex merely.

Classification of various manifestations of benign positional paroxysmal nystagmus, due to canalolithiasis or to cupulolithiasis, as a reaction to movements and to the site of detritus, is now possible due to the integration of theoretical knowledge (relationships between the semicircular canals and/or ampullae and the vestibulo-ocular pathways) with the forms of nystagmus induced when the head is placed in various positions. A comparison is made of results in patients examined in three Departments, during the past 3 years, and data presented in the literature. Findings are presented in a database which enables the clinician to compare the standard diagnostic manoeuvres (Dix-Hallpike, Pagnini-McClure, Rose) with results obtained by placing the head in alternative positions. This approach offers all the information needed to identify the site of onset and hence to formulate a correct diagnosis, thus directly indicating the most appropriate liberating or repositioning manoeuvre or--in the case of a suspected central lesion--to suggest further tests. Moreover, it is suggested that this table could become a useful tool for teaching purposes.

The aim of this study was to characterize the error pattern of continuously tracking the perceived earth-vertical during roll rotations from upright to right or left ear-down and from right or left ear-down to upright. We compared the tracking responses of two paradigms, which either continuously activated the otoliths organs alone (constant velocity tilt) or both the otolith organs and the semicircular canals (constant acceleration tilt). The tracking responses of the subjective visual vertical showed characteristic differences depending on starting position and tilt direction relative to gravity. The error patterns in the constant-velocity and constant-acceleration tilt paradigm were reversed. Estimations during tracking, when otolith information was continuously changing, were more precise compared to estimations following fast tilts to fixed roll tilt positions. We conclude that the central processing underlying these perceptual tracking responses requires, besides the otolith input, information from the vertical semicircular canals.

The vestibular nuclei and the interstitial nucleus of Cajal (INC) have been regarded as key elements of the velocity-to-position integrator for vertical eye movements. This paper reports a class of type II vestibular neurons that receives input from the INC and carries vertical eye movement signals that appear to represent an intermediate stage of the integration process. Extracellular recordings were made from neurons in and near the vestibular nuclei in alert cats. We encountered 39 neurons that exhibited an intense burst of spikes for downward saccades and a position-related tonic activity during intersaccadic intervals (d-type II neurons). They had a very high saccadic sensitivity (4.3+/-2.7 spikes/deg, mean +/- SD) as well as a high position sensitivity (3.2+/-1.6 (spikes/sec)/deg). Unlike the bursts of motoneurons, the bursts of these neurons declined gradually with an exponential-like time course and lasted well beyond the end of saccades. The mean time constant of the burst decay was 139+/-43 ms. The d-type II neurons were excited with disynaptic or trisynaptic latencies following stimulation of the contralateral vestibular nerve. The responses to vertical head rotations suggested inputs from the contralateral posterior canal. The d-type II neurons were excited with short latencies following stimulation of the ipsilateral INC, suggesting that they receive a direct excitatory input from vertical eye movement-related INC neurons with downward on-directions. The d-type II neurons were located in the rostral portion of the vestibular nuclei and the underlying reticular formation. These results suggest that d-type II neurons may be interposed between the burst-tonic neurons in the INC and pure tonic neurons in the vestibular nuclei and contribute to the oculomotor velocity-to-position integration.

Background: The aim of this study was, to establish, if a selective thermal warm-stimulation using monochromatic near infrared radiation (NIR) in healthy persons, patients with chronic otitis media (chronic mucosal inflammation) and after radical surgery of one ear shows quantitative or qualitative changes of the nystagmus reaction., Patients and Methods: Healthy persons (n = 3), patients with a large central defect of the tympanic membrane (n = 5) and after radical ear surgery (n = 6) were examined. In healthy persons a stimulation with monochromatic NIR (lambda = 980 nm) of several areals of the external auditory canal was performed. In patients with large defects of the tympanic membrane the promontorium was stimulated. In patients with a radical cave of the ear a selective NIR-stimulation of the region of the vertical and the anterior semicircular canal was performed. The horizontal semicircular canal was visible as a landmark. Registration of the nystagmus was performed by means of videonystagmography., Results: In healthy persons the mean slow phase velocity of the nystagmus depended on the stimulated region. But there was no qualitative change of three dimensional eye movement. Stimulation of the promontorium showed a strong directional horizontal nystagmus. In patients with a radical cave the stimulation of the regions of the three semicircular canals showed a qualitative difference in three dimensional eye movement. NIR-stimulation showed in all cases a nystagmus into the stimulated ear., Conclusions: The method of monochromatic near infrared stimulation can be used for selective stimulation of several regions of the external auditory canal, the promontorium and the regions of the semicircular canals in a radical cave of the ear as well as to prove the warm reaction of the equilibrium organ. A specific nystagmus after stimulation of the semicircular canal-region in a radical cave of the ear could be an indication for a normal semicircular canal function.

The ability to simultaneously move in the world and maintain stable visual perception depends critically on the contribution of vestibulo-ocular reflexes (VORs) to gaze stabilization. It is traditionally believed that semicircular canal signals drive compensatory responses to rotational head disturbances (rotational VOR), whereas otolith signals compensate for translational movements [translational VOR (TVOR)]. However, a sensory ambiguity exists because otolith afferents are activated similarly during head translations and reorientations relative to gravity (i.e., tilts). Extra-otolith cues are, therefore, necessary to ensure that dynamic head tilts do not elicit a TVOR. To investigate how extra-otolith signals contribute, we characterized the temporal and viewing distance-dependent properties of a TVOR elicited in the absence of a lateral acceleration stimulus to the otoliths during combined translational/rotational motion. We show that, in addition to otolith signals, angular head position signals derived by integrating sensory canal information drive the TVOR. A physiological basis for these results is proposed in a model with two distinct integration steps. Upstream of the well known oculomotor velocity-to-position neural integrator, the model incorporates a separate integration element that could represent the "velocity storage integrator," whose functional role in the oculomotor system has so far remained controversial. We propose that a key functional purpose of the velocity storage network is to temporally integrate semicircular canal signals, so that they may be used to extract translation information from ambiguous otolith afferent signals in the natural and functionally relevant bandwidth of head movements.

The eye movement component that rotates around the line of sight, i.e., the ocular torsion, is in many aspects different from horizontal and vertical eye movements. While ocular torsion is mediated only by reflexive pathways like the torsional vestibulo-ocular and optokinetic reflexes (TVOR and OKN, respectively), horizontal and vertical components are also subject to intentional control mechanisms that are mediated by the saccadic and the pursuit systems. Dynamic properties of torsional eye movements are also very distinct. While horizontal and vertical VOR components show a gain close to unity and a small neural integration leakage with a time constant around pi=30 s, the TVOR shows a smaller gain of 0.4 and also a greater leakage with pi=2 s. During slow head rotations in roll, the TVOR is even less compensatory. At small stimulation levels the gain drops to a value of 0.2 and proves thus to be nonlinear, i.e., to depend on the stimulus magnitude. In a recent study, we hypothesized that this nonlinearity might be the result of a nonlinear processing of nystagmus quick phases rather than a nonlinearity in direct or integrator TVOR pathways. In the present study, we experimentally tested this hypothesis by measuring ocular torsion responses at different head rotation speeds. In addition to the conventional approach of analyzing slow-phase velocity (SPV) gains, we also analyzed properties of nystagmus quick phases. This method proved to be suitable for determining whether nonlinear processing of nystagmus frequency is responsible for the TVOR nonlinearity.

This study provides the first systematic examination of the effects of intratympanic gentamicin instillation on vestibulo-ocular responses of guinea pigs during both Earth-vertical yaw axis and off-vertical axis rotation. A scleral search coil was sutured to the right eye of pigmented female guinea pigs prior to trans-bullar instillation of a 0.2-ml bolus of either 20 mg/ml or 40 mg/ml of gentamicin (1) into the right middle ear (unilateral treatment groups) or (2) into both ears (bilateral treatment groups). Two weeks later, eye movement responses were tested during yaw axis sinusoidal rotation at 7 frequencies (0.02, 0.05, 0.1, 0.2, 0.5, 1 and 2 Hz, 40 deg/s peak velocity) and during off-vertical axis rotation at five constant velocities (20, 40, 60, 80 and 100 deg/s), tilted 30 deg relative to the earth-vertical axis. The main result was that unilateral trans-bullar gentamicin instillation produced almost exclusively unidirectional deficits in horizontal angular vestibulocular reflex (HVOR) responses and modulation and bias responses to off-vertical axis rotation (OVAR). The HVOR gain was reduced during rotation toward the injected ear in a dose-dependent manner for frequencies of 1 Hz and lower, but there was no effect on responses during rotation toward the intact ear. Further, the modulation and bias responses to OVAR were reduced profoundly in a dose-dependent manner during rotation toward the treated ear. It is suggested that these effects indicate selective cytotoxic and/or physiologic effects of gentamicin intoxication in the inner ear or, possibly, the vestibular nerve and central nervous system.

The aim of this study was to test the hypothesis that optimal activation of both the semicircular canals and the otoliths provides reliable vestibular cues about self-orientation in space. For this, we measured the ability of subjects to estimate the subjective vertical immediately, 20 s and 90 s after a rapid tilt (180 degrees /s(2)) from upright into different roll positions between 90 degrees left and right side down. Subjects had to estimate the earth-vertical and earth-horizontal direction in the dark by (a) setting a luminous line, (b) performing saccades, and (c) verbally declaring body position relative to gravity. The mean error curves from the three paradigms showed consistent E (Müller)- and A (Aubert)-effects, which did not significantly change over time. Horizontal and vertical saccade tasks exhibited different response characteristics, as previously reported by others, which likely reflect different computation mechanisms. The verbal estimation paradigm yielded complementary results to those of the luminous line paradigm and vertical saccade task. The E-effect of the luminous line and the vertical saccade paradigm might be explained by a bias towards earth-vertical due to interactions of vestibular and neck afferent signals. The invariably small A-effect of the luminous line and the vertical saccade paradigm probably reflects somatosensory signals that had relatively weak influence in our experiments. We conclude that phasic activation of the vestibular system reduces the influence of non-vestibular cues observed in low tilt velocity or static experiments. Although this activation generates an E-effect, the total error in the range of +/-90 degrees is reduced.

To investigate whether the primary planes of eye and body responses to galvanic vestibular stimulation (GVS) are congruent, we have measured the binocular, three-dimensional eye movements (scleral coil technique) to bilateral bipolar GVS in six normal human subjects. Stimulation intensities were kept deliberately low in order to characterize the response to near-threshold intensities of stimulation (0.1-0.9 mA) that had been used previously to characterise body postural responses. Stimuli were applied for 4 s, but only the early responses that occurred within the initial 300 ms of turning the current on or off were measured. At intensities of 0.1-0.7 mA the 'on' response consisted almost exclusively of a torsional slow phase eye movement in which the top of the eyes rotated towards the anode. The latency of the torsional response was ca. 46 ms. A weak polarity-dependent disconjugate response was also observed in which the intorting eye elevated and the extorting eye depressed ('skew eye deviation'). When the current was turned off similar responses occurred in the reverse direction. Removal of the visual fixation light-emitting diode (LED) had no consistent effect on the short-latency ocular responses. The direction of the ocular response was similar to that of the postural response and is compatible with GVS inducing an apparent dynamic roll-tilt of the head towards the cathode. However, weak horizontal eye movements, which became more prominent as the stimulus intensity was increased to 0.9 mA, were also observed. This suggests that an additional weak rotational component about the yaw axis, or a component of lateral translation in the frontal plane, is contained in the GVS-evoked signal. The overall pattern of eye movement suggests that semicircular canal afferents contribute to these low-intensity GVS responses.

The semi-circular canals and the otolith organs both contribute to gaze stabilization during head movement. We investigated how these sensory signals interact when they provide conflicting information about head orientation in space. Human subjects were reoriented 90 degrees in pitch or roll during long-duration, constant-velocity rotation about the earth-vertical axis while we measured three-dimensional eye movements. After the reorientation, the otoliths correctly indicated the static orientation of the subject with respect to gravity, while the semicircular canals provided a strong signal of rotation. This rotation signal from the canals could only be consistent with a static orientation with respect to gravity if the rotation-axis indicated by the canals was exactly parallel to gravity. This was not true, so a cue-conflict existed. These conflicting stimuli elicited motion sickness and a complex tumbling sensation. Strong horizontal, vertical, and/or torsional eye movements were also induced, allowing us to study the influence of the conflict between the otoliths and the canals on all three eye-movement components. We found a shortening of the horizontal and vertical time constants of the decay of nystagmus and a trend for an increase in peak velocity following reorientation. The dumping of the velocity storage occurred regardless of whether eye velocity along that axis was compensatory to the head rotation or not. We found a trend for the axis of eye velocity to reorient to make the head-velocity signal from the canals consistent with the head-orientation signal from the otoliths, but this reorientation was small and only observed when subjects were tilted to upright. Previous models of canal-otolith interaction could not fully account for our data, particularly the decreased time constant of the decay of nystagmus. We present a model with a mechanism that reduces the velocity-storage component in the presence of a strong cue-conflict. Our study, supported by other experiments, also indicates that static otolith signals exhibit considerably smaller effects on eye movements in humans than in monkeys.

The sensory weighting model is a general model of sensory integration that consists of three processing layers. First, each sensor provides the central nervous system (CNS) with information regarding a specific physical variable. Due to sensor dynamics, this measure is only reliable for the frequency range over which the sensor is accurate. Therefore, we hypothesize that the CNS improves on the reliability of the individual sensor outside this frequency range by using information from other sensors, a process referred to as "frequency completion." Frequency completion uses internal models of sensory dynamics. This "improved" sensory signal is designated as the "sensory estimate" of the physical variable. Second, before being combined, information with different physical meanings is first transformed into a common representation; sensory estimates are converted to intermediate estimates. This conversion uses internal models of body dynamics and physical relationships. Third, several sensory systems may provide information about the same physical variable (e.g., semicircular canals and vision both measure self-rotation). Therefore, we hypothesize that the "central estimate" of a physical variable is computed as a weighted sum of all available intermediate estimates of this physical variable, a process referred to as "multicue weighted averaging." The resulting central estimate is fed back to the first two layers. The sensory weighting model is applied to three-dimensional (3D) visual-vestibular interactions and their associated eye movements and perceptual responses. The model inputs are 3D angular and translational stimuli. The sensory inputs are the 3D sensory signals coming from the semicircular canals, otolith organs, and the visual system. The angular and translational components of visual movement are assumed to be available as separate stimuli measured by the visual system using retinal slip and image deformation. In addition, both tonic ("regular") and phasic ("irregular") otolithic afferents are implemented. Whereas neither tonic nor phasic otolithic afferents distinguish gravity from linear acceleration, the model uses tonic afferents to estimate gravity and phasic afferents to estimate linear acceleration. The model outputs are the internal estimates of physical motion variables and 3D slow-phase eye movements. The model also includes a smooth pursuit module. The model matches eye responses and perceptual effects measured during various motion paradigms in darkness (e.g., centered and eccentric yaw rotation about an earth-vertical axis, yaw rotation about an earth-horizontal axis) and with visual cues (e.g., stabilized visual stimulation or optokinetic stimulation).

We recorded three-dimensional eye movements elicited by velocity steps about axes that were tilted with respect to the earth-vertical. Subjects were accelerated in 1 s from zero to 100 degrees/s, and the axis of rotation was tilted by 15 degrees, 30 degrees, 60 degrees, or 90 degrees. This stimulus induced a constant horizontal velocity component that was directed opposite to the direction of rotation, as well as a modulation of the horizontal, vertical and torsional components with the frequency of the rotation. The maximum steady-state response in the horizontal constant-velocity component was much smaller than in other species (about 6 degrees/s), reaching a maximum at a tilt angle of about 60 degrees. While the amplitude of the horizontal modulation component increased up to a tilt angle of 90 degrees (8.4 degrees/s), the vertical and torsional modulation amplitudes saturated around 60 degrees (ca. 2.5 degrees/s). At small tilt angles, the horizontal modulation component showed a small phase lag with respect to the chair position, which turned into a small phase lead at large tilt angles. The torsional component showed a phase lead that increased with increasing tilt angle. The vertical and torsional velocity modulation at large tilt angles was not predicted by a recent model of otolith-canal interaction by Merfeld. Agreement between model and experimental data could be achieved, however, by introducing a constant force along the body's z-axis to compensate for the gravitational pull on the otoliths in the head-upright position. This approach had been suggested previously to explain the direction of the perceived subjective vertical during roll under different g-levels, and produced in our model the observed vertical and torsional modulation components at large tilt angles.

During sustained constant velocity and low-frequency off-vertical axis rotations (OVAR), otolith signals contribute significantly to slow-phase eye velocity. The adaptive plasticity of these responses was investigated here after semicircular canal plugging. Inactivation of semicircular canals results in a highly compromised and deficient vestibulo-ocular reflex (VOR). Based on the VOR enhancement hypothesis, one could expect an adaptive increase of otolith-borne angular velocity signals due to combined otolith/canal inputs after inactivation of the semicircular canals. Contrary to expectations, however, the steady-state slow-phase velocity during constant velocity OVAR decreased in amplitude over time. A similar progressive decrease in VOR gain was also observed during low-frequency off-vertical axis oscillations. This response deterioration was present in animals with either lateral or vertical semicircular canals inactivated and was limited to the plane(s) of the plugged canals. The results are consistent with the idea that the low-frequency otolith signals do not simply enhance VOR responses. Rather, the nervous system appears to correlate vestibular sensory information from the otoliths and the semicircular canals to generate an integral response to head motion.

Vestibular information modulates hippocampal activity for spatial processing and place cell firing. However, evidence of a purely vestibular stimulus modulating hippocampal activity is confounded as most studies use stimuli containing somatosensory and visual components. In the present study, high-frequency electrical stimulation of specific vestibular sensory regions of the right labyrinth in anaesthetized guinea pigs induced an evoked field potential in the hippocampal formation bilaterally with a latency of about 40 ms following stimulation onset. Field potentials localized in the hippocampal formation occurred with stimulus current parameters that were too small to produce eye movements. This provides direct electrophysiological evidence of vestibular input to the hippocampus.

Bilateral galvanic vestibular stimulation (GVS) with current intensity of 3 mA was applied at mastoid level in 11 patients with chronic bilateral vestibular failure, in order to determine ocular motor responses by 3-D video-oculography. The following abnormal features were found: (1) a predominantly torsional or mixed torsional-horizontal nystagmus at the onset of stimulation with lower current intensities (1.0-3.0 mA) in nine patients; (2) a reduced amplitude of tonic ocular torsion by about 50% in nine patients (1.3 +/- 0.6 degrees at 3 mA); (3) a nystagmus in the opposite direction at stimulation offset in five patients (rebound); (4) no eye movements at all in a patient with bilateral nerve failure. GVS stimulates the vestibular nerve, thus allowing differentiation of nerve failure from labyrinthine failure. The low thresholds for initiating nystagmus and the rebound, which appear to be the most typical features of bilateral labyrinthine failure, can be explained by central compensation mechanisms.

New evidence for a central resolution of gravito-inertial signals has been recently obtained by analyzing the properties of the vestibulo-ocular reflex (VOR) in response to combined lateral translations and roll tilts of the head. It is found that the VOR generates robust compensatory horizontal eye movements independent of whether or not the interaural translatory acceleration component is canceled out by a gravitational acceleration component due to simultaneous roll-tilt. This response property of the VOR depends on functional semicircular canals, suggesting that the brain uses both otolith and semicircular canal signals to estimate head motion relative to inertial space. Vestibular information about dynamic head attitude relative to gravity is the basis for computing head (and body) angular velocity relative to inertial space. Available evidence suggests that the inertial vestibular system controls both head attitude and velocity with respect to a gravity-centered reference frame. The basic computational principles underlying the inertial processing of otolith and semicircular canal afferent signals are outlined.

The effect of changes in static and dynamic gravity signals on the phase accuracy of the horizontal vestibulo-ocular reflex (HVOR) was studied in rats using chronically implanted scleral search coils to monitor eye movements. Rats were sinusoidally rotated using a range of different frequencies (0.035-2 Hz) in a plane which always activated the horizontal semicircular canals but in one of three different orientations with regard to gravity which differentially activated the otolith organs: 1) upright-normal static gravity signal, no dynamic otolith activation; 2) inverted-inverted static gravity signal, no dynamic otolith activation; 3) on-side-dynamic activation of the otolith organs. In the upright orientation, the HVOR shows a phase advance at 0.2 Hz and below but not at 0.5 Hz and above. Phase accuracy of the HVOR was further degraded in the inverted orientation with rats showing large phase leads at 0.2 Hz and below. In contrast, accuracy of the HVOR was significantly improved at 0.2 Hz and below in the on-side orientation with phase accurate eye movements down to the lowest frequency tested. The results further support the idea that otolith organs play an important role in VOR generation by supplementing the semicircular canals' response to angular head movements.

Objective: The aim of this study was to determine the otolithic and semicircular canal effects of galvanic vestibular stimulation with increasing current strengths on eye movements and the perception of verticality., Methods: We measured (1) 3-dimensional eye movements, (2) subjective tilt of the peripheral visual field, and (3) subjective tilt of a central vertical line in 12 healthy subjects during galvanic vestibular stimulation. A rectangular, unipolar binaural electric current was applied to each subject's mastoid., Results: Anodal stimulation of the right mastoid led to an ipsiversive tonic ocular torsion of up to 5.4 degrees, to a contralateral tilt of both the peripheral visual field (1-9 degrees), and a central vertical line (0.5-6.2 degrees) increasing in amplitude with increasing current strengths applied. This reflects otolith stimulation. In most subjects, current strengths of 3 mA or more elicited a slight (horizontal-) torsional nystagmus (amplitude 1-2 degrees) that was superimposed on static torsion. This reflects horizontal and vertical semicircular canal stimulation. A correlation was found in the amount of the 3 measured parameters and the strength of the applied current., Conclusions: Thus, galvanic vestibular stimulation at low current intensities (1-3 mA) preferably excites otolith responses, which increase with increasing current intensity. With higher current intensity above 3 mA, additional semicircular canal responses are elicited in the form of horizontal-rotatory nystagmus superimposed on static torsional deviations. The lack of a vertical deviation and nystagmus can be explained by the counterdirected vertical components of the anterior and posterior semicircular canal.

This article summarizes six recent degree-of-freedom studies of visual-vestibular interaction during natural activities and relates the findings to canal-otolith interactions evaluated during eccentric axis rotations. Magnetic search coils were used to measure angular eye and head movements of young and elderly subjects. A flux gate magnetometer was used to measure three-dimensional head translation. Three activities were studied: standing quietly, walking in place, and running in place. Each activity was evaluated with three viewing conditions: a visible target viewed normally, a remembered target in darkness, and a visible target viewed with x2 binocular telescopic spectacles. Canal-otolith interaction was assessed with passive, whole-body, transient, and steady-state rotations in pitch and yaw at multiple frequencies about axes that were either oculocentric or eccentric to the eyes. For each rotational axis, subjects regarded visible and remembered targets located at various distances. Horizontal and vertical angular vestibulo-ocular reflexes were demonstrable in all subjects during standing, walking, and running. When only angular gains were considered, gains in both darkness and during normal vision were less than 1.0 and were generally lower in elderly than in young subjects. Magnified vision with x2 telescopic spectacles produced only small gain increases as compared with normal vision. During walking and running all subjects exhibited significant mediolateral and dorsoventral head translations that were antiphase locked to yaw and pitch head movements, respectively. These head translations and rotations have mutually compensating effects on gaze in a target plane for typical viewing distances and allow angular vestibulo-ocular reflex gains of less than 1.0 to be optimal for gaze stabilization during natural activities. During passive, whole-body eccentric pitch and yaw head rotations, vestibulo-ocular reflex gain was modulated as appropriate to stabilize gaze on targets at the distances used. This modulation was evident within the first 80 msec of onset of head movement, too early to be caused by immediate visual tracking. Modeling suggests a linear interaction between canal signals and otolith signals scaled by the inverse of target distance. Vestibulo-ocular reflex performance appears to be adapted to stabilize gaze during translational and rotational perturbations that occur during natural activities, as is appropriate for relevant target distances. Although immediate visual tracking contributes little to gaze stabilization during natural activities, visual requirements determine the performance of vestibulo-ocular reflexes arising from both canals and otoliths.

The purpose of this study was to investigate changes in neck muscle and eye movement responses during the early stages of vestibular compensation (first 3 weeks after unilateral vestibular neurectomy, UVN). Electromyographic (EMG) activity from antagonist neck extensor (splenius capitis) and flexor (longus capitis) muscles and eye movements were recorded during sinusoidal visual and/or otolith vertical linear stimulations in the 0.05-1 Hz frequency range (corresponding acceleration range 0.003-1.16 g) in the head-fixed alert cat. Preoperative EMG activity from the splenius and longus capitis muscles showed a pattern of alternate activation of the antagonist neck muscles in all the cats. After UVN, two motor strategies were observed. For three of the seven cats, the temporal activation of the individual neck muscles was the same as that recorded before UVN. For the other four cats, UVN resulted in a pattern of coactivation of the flexor and extensor neck muscles because of a phase change of the splenius capitis. In both subgroups, the response patterns of the antagonist neck muscles were consistent for each cat independently of the experimental conditions, throughout the 3 weeks of testing. Cats displaying alternate activation of antagonist neck muscles showed an enhanced gain of the visually induced neck responses, particularly in the high range of stimulus frequency, and a gain decrease in the otolith-induced neck responses at the lowest frequency (0.25 Hz) only. By contrast, for cats with neck muscle coactivation, the gain of the visually induced neck responses was basically unaffected relative to preoperative values, whereas otolith-induced neck responses were considerably decreased in the whole range of stimulation. As concerns oculomotor responses, results in the two subgroups of cats were similar. The optokinetic responses were not affected by the vestibular lesion. On the contrary, otolith-induced eye responses showed a gain reduction and a phase lead. Deficits and short-term changes after UVN of otolith- and semicircular canal-evoked collic and ocular responses are compared.

We studied the human vestibulo-ocular reflex (VOR) in response to head 'impulses': brief, unpredictable, passive, high-acceleration (up to 4000 degrees/s2), low-amplitude (20-30 degrees) head rotations. We delivered the head impulses approximately in the plane of the semicircular canal (SCC) being tested. To test the anterior and posterior SCCs, the head impulses were delivered in a diagonal plane, midway between the frontal (roll) and sagittal (pitch) planes. We recorded head and eye position in three dimensions with scleral search coils in nine normal subjects, seven patients following unilateral surgical vestibular neurectomy and three patients following unilateral posterior SCC occlusion. In the post-surgical patients we demonstrated a severe, permanent VOR gain deficit (0.2-0.3) for head impulses directed toward any single non-functioning SCC. The sensitivity of the test depends on the physiological properties of primary vestibular afferents, and its specificity depends on the anatomical orientation of the SCCs. The diagonal head impulse is the first test of individual vertical SCC function in humans, and together with the horizontal head impulse, forms a comprehensive battery of SCC-plane tests. These canal-plane impulses could be useful in evaluating patients with vertigo or other vestibular disorders.

Three normal human subjects were oscillated about their naso-occipital axis in a supine position at 0.4 Hz and 0.1 Hz, both in darkness and in the light with a structured fixation target. The same subjects were oscillated in roll about an upright position, at the same frequencies, in darkness; and also about axes directed 20 degrees and 40 degrees to the left and to the right of the midsagittal plane, at 0.4 Hz, in darkness. Three-dimensional binocular eye movements were recorded using video-oculography. All stimuli induced a predominantly torsional nystagmus with small disconjugate head-vertical (skew) and conjugate head-horizontal components. For roll oscillation, the torsional slow phase velocity gain was higher in the light and generally increased with the stimulation frequency. In darkness, only one subject had significantly higher torsional gains in the upright compared to the supine position (12% difference), suggesting that the otolith contribution to the roll response is minimal at the frequencies tested. The slow phase velocity gain of the skew increased with fixation in two subjects. but decreased in the third subject; these changes were related to changes in eye vergence. In the upright position, with oblique axes of rotation, the head-vertical eye movements were asymmetrical, with the outermost eye executing a larger amplitude movement. The disconjugate head-vertical eye movements observed can be explained by the pattern of vertical semicircular canal stimulation and their connections to the extraocular muscles. In humans, skewing of the eyes may compensate for the eccentricity of the foveae which lie in the temporal retina and undergo vertical translations in opposite directions when the eyes tort.

Hypothesis and Background: Quantitative caloric testing is considered to be one of the most sensitive parameters in the diagnosis of peripheral vestibular disorders. In the past, because of limitations in the methods, the evaluation of the caloric response was restricted to mainly lateral semicircular canal functions. In this study, the authors tried to extend caloric testing to the function of all semicircular canals by using three-dimensional (3-D) analysis techniques., Methods: The authors studied in seven normal subjects 3-D eye movement responses to air caloric of the right ear with the subjects positioned in standard caloric position (lateral semicircular canal vertical) or such that one of the three semicircular canals of the right side was horizontal. Movement of the left eye was measured in 3-D with a dual-magnetic search coil. During stimulation, 10 seconds of maximum response were selected and desaccaded to yield the slow-phase velocity profile. From this profile, the average magnitude and direction of the eye rotation axis (velocity vector) were calculated in head coordinates., Results: In all subjects, in standard caloric position, warm caloric produced eye velocity vectors that clustered closely along the direction expected from an excitation of the right lateral semicircular canal. When the subjects were positioned with one of the vertical semicircular canals horizontal, the orientation of the velocity vectors shifted toward a direction expected from the combined excitation of the lateral and the other vertical semicircular canal and vice versa., Conclusions: The 3-D eye movement recordings during caloric stimulation in different head positions allow the evaluation of the function of all semicircular canals.

1. Secondary position-vestibular-pause (PVP) neurons in the vestibuloocular reflex (VOR) pathway of adult rhesus monkeys were studied during combined semicircular canal and otolith stimulation. The head was rotated at 0.5 Hz with the axis of rotation centered between the otolith organs (on-axis, ON) and with the axis of rotation 23 cm in front of the otoliths (off-axis, OFF). Both conditions were tested with two different vergence angles by the use of 14-cm (near target, NT) and 100-cm (far target, FT) targets. 2. The tangential translational stimulus to the otoliths in the OFF trials should result in a compensatory eye movement that is opposite in direction to that resulting from the angular stimulus to the canals. The otolith stimulus should be great enough to reverse the eye movement response in the NT OFF trials according to geometric calculations. This reversal in eye movement direction occurred as expected although the latency of the reversal (70 ms) was somewhat greater than expected and the magnitude of the reversal was less than predicted solely on the basis of geometric considerations. 3. The responses of the PVP neurons were corrected for eye position sensitivity to investigate the head movement response components. The amplitude of the response in 22 of 24 PVP cells was reduced in the NT OFF condition compared with the FT OFF condition. This difference was not sufficient in itself to explain the observed reversal in eye movement response. 4. The average sensitivities of the neurons to rotation during the FT and NT ON trials were 1.38 and 1.41 spikes.s-1.deg-1.s-1, respectively. This is too small an increase to account for the increase in the angular VOR gain with near targets (approximately 25%); therefore cells other than PVP neurons must be responsible. 5. The average sensitivities of the PVP neurons to translational accelerations obtained from the FT and NT OFF trials were 305 and 484 spikes.s-1.g-1, respectively, which is higher than most otolith afferent sensitivities reported for 0.5-Hz stimuli in the literature. The otolith component is modified by ocular convergence (59% increase in sensitivity), but this increase is too small to account for the change in the translational VOR gain between the two conditions. 6. Although recordings were only obtained from seven eye-head-velocity cells, the results indicate that these neurons may provide the additional signals not present in the PVP cells. These neurons exhibited large differences between ON and OFF rotations and were found to substantially increase their modulation during the NT conditions compared with that observed during the FT conditions.

The vestibulo-ocular reflex (VOR) was studied in three squirrel monkeys subjected to rotations with the head either centered over, or displaced eccentrically from, the axis of rotation. This was done for several different head orientations relative to gravity in order to determine how canal-mediated angular (aVOR) and otolith-mediated linear (IVOR) components of the VOR are combined to generate eye movement responses in three-dimensional space. The aVOR was stimulated in isolation by rotating the head about the axis of rotation in the upright (UP), right-side down (RD), or nose-up (NU) orientations. Horizontal and vertical aVOR responses were compensatory for head rotation over the frequency range 0.25-4.0 Hz, with mean gains near 0.9. The horizontal aVOR was relatively constant across the frequency range, while vertical aVOR gains increased with increasing stimulation frequency. In the NU orientation, compensatory torsional aVOR responses were of relatively low gain (0.54) compared with horizontal and vertical responses, and gains remained constant over the frequency range. When the head was displaced eccentrically, rotation provided the same angular stimuli but added linear stimulus components, due to the centripetal and tangential accelerations acting on the head. By manipulating the orientation of the head relative to gravity and relative to the axis of rotation, the IVOR response could be combined with, or isolated from, the aVOR response. Eccentric rotation in the UP and RD orientations generated aVOR and IVOR responses which acted in the same head plane. Horizontal aVOR-IVOR interactions were recorded when the head was in the UP orientation and facing toward ("nose-in") or away from ("nose-out") the rotation axis. Similarly, vertical responses were recorded with the head RD and in the nose-out or nose-in positions. For both horizontal and vertical responses, gains were dependent on both the frequency of stimulation and the directions and relative amplitudes of the angular and linear motion components. When subjects were positioned nose-out, the angular and linear stimuli produced synergistic interactions, with the IVOR driving the eyes in the same direction as the aVOR. Gains increased with increasing frequency, consistent with an addition of broad-band aVOR and high-pass IVOR components. When subjects were nose-in, angular and linear stimuli generated eye movements in opposing directions, and gains declined with increasing frequency, consistent with a subtraction of the IVOR from the aVOR. This response pattern was identical for horizontal and vertical eye movements. aVOR and IVOR interactions were also assessed when the two components acted in orthogonal response planes. By rotating the monkeys into the NU orientation, the aVOR acted primarily in the roll plane, generating torsional ocular responses, while the translational (IVOR) component generated horizontal or vertical ocular responses, depending on whether the head was oriented such that linear accelerations acted along the interaural or dorsoventral axes, respectively. Horizontal and vertical IVOR responses were negligible at 0.25 Hz and increased dramatically with increasing frequency. Comparison of the combined responses (UP and RD orientations) with the isolated aVOR (head-centered) and IVOR (NU orientation) responses, indicates that these VOR components sum in a linear fashion during complex head motion.

Selective semicircular canal inactivation and three-dimensional eye movement recordings have been used to investigate the spatial organization of vestibular signals in the vestibulo-ocular reflex (VOR) of rhesus monkeys. In animals with one pair of semicircular canals inactivated, afferent activity no longer codes all spatial components of head angular velocity. if it were the activation pattern of semicircular canal afferents alone that determines VOR slow phase eye velocity, the head velocity components along the sensitivity vectors of the remaining intact semicircular canals would determine the orientation of slow phase eye velocity. Thus, angular head velocity and slow phase eye velocity would not necessarily always align. Alternatively, if vestibulo-ocular signals coded absolute angular head motion in space based on both semicircular canal and otolith afferent information, one might expect a spatial transformation of the encoded head angular velocity signals such that slow phase eye velocity and angular head velocity continue to spatially align. Examination of the VOR at different frequencies between 0.01 Hz and 1 Hz revealed a frequency-specific spatial organization of vestibulo-ocular signals. Mid and high frequency vestibulo-ocular responses were determined exclusively by the orientation of the sensitivity vectors of the remaining intact semicircular canals. In contrasts, low frequency vestibulo-ocular responses were largely determined by the orientation of the head relative to gravity. These low frequency responses after selective semicircular canal inactivation could be predicted and simulated by a simple model where semicircular canal signals are spatially transformed from a head-fixed to a space-fixed (inertial) representation of angular head velocity. These findings suggest that low frequency vestibulo-ocular responses are dominated by inertial vestibular signals that detect absolute head motion in space based on both semicircular canal and otolith afferent information. Inertial vestibular signals are likely to contribute to head control and motor coordination of gaze, head and body posture.

Recent results by Wearne [(1993) Ph.D. thesis] using the scleral search-coil method of measuring eye position indicate that changes in ocular torsion position (OTP) occur during yaw angular acceleration about an earth vertical axis. The present set of experiments, using an image processing method of eye movement measurement free from the possible confound of search coil slippage, demonstrates the generality and repeatability of this phenomenon and examines its possible causes. The change in torsion position is not a linear vestibulo-ocular reflex (LVOR) response to interaural linear acceleration stimulation of the otoliths, but rather the effect is dependent on the characteristics of the angular acceleration stimulus, commencing at the onset and decaying at the offset of the angular acceleration. In the experiments reported here, the magnitude of the angular acceleration stimulus was varied and the torsion position response showed corresponding variations. We consider that the change in torsion position observed during angular acceleration is most likely to be due to activity of the semicircular canals.

A hydraulically driven, digitally servo-controlled multi-axes rotary chair is described. This device generates motion profiles with the subjects head in the center of rotation mainly in order to adequately stimulate the semicircular canals which are sensitive sensors for angular accelerations. This newly developed apparatus allows for motion stimuli which are below the vestibular threshold up to accelerations of 12 rad/s2 (688 degrees/s2) and is thus suitable for a variety of experiments in the field of vestibular, oculomotor, and intersensory research in 3-dimensional space.