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Previous studies to expand the scope of prosthetic stimulation of the otolith end organs showed that selective stimulation of the utricle and saccule is possible. This article further defines those possibilities by characterizing a diseased animal model and subsequently studying its responses to electrical stimulation alone and in combination with mechanical motion. We show that we can partially restore responses to tilt and translation in animals with unilateral gentamicin ototoxic injury and contralateral surgical disruption.

Head rotation, translation, and tilt with respect to a gravitational field elicit reflexive eye movements that partially stabilize images of Earth-fixed objects on the retinas of humans and other vertebrates. Compared with the angular vestibulo-ocular reflex, responses to translation and tilt, collectively called the otolith-ocular reflex (OOR), are less completely characterized, typically smaller, generally disconjugate (different for the 2 eyes) and more complicated in their relationship to the natural stimuli that elicit them. We measured binocular 3-dimensional OOR responses of 6 alert normal chinchillas in darkness during whole body tilts around 16 Earth-horizontal axes and translations along 21 axes in horizontal, coronal, and sagittal planes. Ocular countertilt responses to 40-s whole body tilts about Earth-horizontal axes grew linearly with head tilt amplitude, but responses were disconjugate, with each eye’s response greatest for whole body tilts about axes near the other eye’s resting line of sight. OOR response magnitude during 1-Hz sinusoidal whole body translations along Earth-horizontal axes also grew with stimulus amplitude. Translational OOR responses were similarly disconjugate, with each eye’s response greatest for whole body translations along its resting line of sight. Responses to Earth-horizontal translation were similar to those that would be expected for tilts that would cause a similar peak deviation of the gravitoinertial acceleration (GIA) vector with respect to the head, consistent with the “perceived tilt” model of the OOR. However, that model poorly fit responses to translations along non-Earth-horizontal axes and was insufficient to explain why responses are larger for the eye toward which the GIA vector deviates. NEW & NOTEWORTHY As the first in a pair of papers on Binocular 3D Otolith-Ocular Reflexes, this paper characterizes binocular 3D eye movements in normal chinchillas during tilts and translations. The eye movement responses were used to create a data set to fully define the normal otolith-ocular reflexes in chinchillas. This data set provides the foundation to use otolith-ocular reflexes to back-project direction and magnitude of eye movement to predict tilt axis as discussed in the companion paper.

Electrical stimulation of vestibular afferent neurons to partially restore semicircular canal sensation of head rotation and the stabilizing reflexes that sensation supports has potential to effectively treat individuals disabled by bilateral vestibular hypofunction. Ideally, a vestibular implant system using this approach would be integrated with a cochlear implant, which would provide clinicians with a means to simultaneously treat loss of both vestibular and auditory sensation. Despite obvious similarities, merging these technologies poses several challenges, including stimulus pulse timing errors that arise when a system must implement a pulse frequency modulation-encoding scheme (as is used in vestibular implants to mimic normal vestibular nerve encoding of head movement) within fixed-rate continuous interleaved sampling (CIS) strategies used in cochlear implants. Pulse timing errors caused by temporal discretization inherent to CIS create stair step discontinuities of the vestibular implant’s smooth mapping of head velocity to stimulus pulse frequency. In this study, we assayed electrically evoked vestibuloocular reflex responses in two rhesus macaques using both a smooth pulse frequency modulation map and a discretized map corrupted by temporal errors typical of those arising in a combined cochlear-vestibular implant. Responses were measured using three-dimensional scleral coil oculography for prosthetic electrical stimuli representing sinusoidal head velocity waveforms that varied over 50–400°/s and 0.1–5 Hz. Pulse timing errors produced negligible effects on responses across all canals in both animals, indicating that temporal discretization inherent to implementing a pulse frequency modulation-coding scheme within a cochlear implant’s CIS fixed pulse timing framework need not sacrifice performance of the combined system’s vestibular implant portion. NEW & NOTEWORTHY Merging a vestibular implant system with existing cochlear implant technology can provide clinicians with a means to restore both vestibular and auditory sensation. Pulse timing errors inherent to integration of pulse frequency modulation vestibular stimulation with fixed-rate, continuous interleaved sampling cochlear implant stimulation would discretize the smooth head velocity encoding of a combined device. In this study, we show these pulse timing errors produce negligible effects on electrically evoked vestibulo-ocular reflex responses in two rhesus macaques.

Sensory pathways provide complex and multifaceted information to the brain. Recent advances have created new opportunities for applying our understanding of the brain to sensory prothesis development. Yet complex sensor physiology, limited numbers of electrodes, and nonspecific stimulation have proven to be a challenge for many sensory systems. In contrast, the vestibular system is uniquely suited for prosthesis development. Its peripheral anatomy allows site-specific stimulation of 3 separate sensory organs that encode distinct directions of head motion. Accordingly, here, we investigated whether implementing natural encoding strategies improves vestibular prosthesis performance. The eye movements produced by the vestibulo-ocular reflex (VOR), which plays an essential role in maintaining visual stability, were measured to quantify performance. Overall, implementing the natural tuning dynamics of vestibular afferents produced more temporally accurate VOR eye movements. Exploration of the parameter space further revealed that more dynamic tunings were not beneficial due to saturation and unnatural phase advances. Trends were comparable for stimulation encoding virtual versus physical head rotations, with gains enhanced in the latter case. Finally, using computational methods, we found that the same simple model explained the eye movements evoked by sinusoidal and transient stimulation and that a stimulation efficacy substantially less than 100% could account for our results. Taken together, our results establish that prosthesis encodings that incorporate naturalistic afferent dynamics and account for activation efficacy are well suited for restoration of gaze stability. More generally, these results emphasize the benefits of leveraging the brain’s endogenous coding strategies in prosthesis development to improve functional outcomes.

Background: A clinical pattern of damage to the auditory, visual, and vestibular sensorimotor systems, known as multi-sensory impairment, affects a significant percent of the US population. Within the population of US military service members exposed to mild traumatic brain injury (mTBI), 15 – 44% will develop multi-sensory impairment following a mild traumatic brain injury. In the US civilian population, multi-sensory impairment related symptoms are also a common sequela of damage to the vestibular system and affect ~ 300-500/100,000 population. Vestibular rehabilitation is recognized as a critical component of the management of multi-sensory impairment. Unfortunately, the current clinical practice guidelines for the delivery of vestibular rehabilitation are not evidence-based and primarily rely on expert opinion. The focus of the INVENT VPT trial is gaze stability training, which represents the unique component of vestibular rehabilitation. The aim of the INVENT VPT trial is to assess the efficacy of a non-invasive, incremental vestibular adaptation training device for normalizing the response of the vestibulo-ocular reflex. Methods: The INVENT VPT trial is a multicenter randomized controlled crossover trial in which military service members with mTBI and civilian patients with vestibular hypofunction are randomized to begin traditional vestibular rehabilitation or incremental vestibular adaptation and then cross over to the alternate intervention after a prescribed washout period. Vestibulo-ocular reflex function and other functional outcomes are measured to identify the best means to improve delivery of vestibular rehabilitation. We incorporate ecologically valid outcome measures that address the common symptoms experienced in those with vestibular pathology and multi-sensory impairment. Discussion: The INVENT VPT Trial will directly impact the health care delivery of vestibular rehabilitation in patients suffering from multi-sensory impairment in three critical ways: 1) Compare optimized traditional methods of vestibular rehabilitation to a novel device that is hypothesized to improve vestibulo-ocular reflex performance; 2) Isolate the ideal dosing of vestibular rehabilitation considering patient burden and compliance rates; 3) Examine whether recovery of the vestibulo-ocular reflex can be predicted in participants with vestibular symptoms. Trial registration: ClinicalTrials.gov, NCT03846830. Registered 20 February 2019,https://clinicaltrials.gov/ct2/show/NCT03846830

Hypothesis Magnetic vestibular stimulation (MVS) elicits nystagmus in C57BL/6J mice but not head tilt mice lacking Nox3, which is required for normal otoconial development. Background Humans have vertigo and nystagmus in strong magnetic fields within magnetic resonance imaging machines. The hypothesized mechanism is a Lorentz force driven by electrical current entering the utricular neuroepithelium, acting indirectly on crista hair cells via endolymph movement deflecting cupulae. We tested an alternate hypothesized mechanism: Lorentz action directly on crista hair cell stereocilia, driven by their currents independent of the utricle. Methods Before MVS, vestibulo-ocular reflex responses of eight C57BL/6J mice and six head tilt mice were measured during whole-body sinusoidal rotations and tilts using video-oculography. Mice were then placed within a 4.7 Tesla magnetic field with the horizontal semicircular canals approximately Earth-horizontal for ≥1 minute in several head orientations, while eye movements were recorded via infrared video in darkness. Results Outside the magnet, both C57BL/6J and head tilt mice had intact horizontal vestibulo-ocular reflex, but only C57BL/6J mice exhibited static counter-roll responses to tilt (normal utiruclo-ocular reflex). When placed in the magnet nose-first, C57BL/6J mice had left-beating nystagmus, lasting a median of 32.8 seconds. When tail-first, nystagmus was right-beating and similar duration (median 28.0 s, p > 0.05). In contrast, head tilt mice lacked magnetic field-induced nystagmus (p Conclusions C57BL/6J mice generate nystagmus in response to MVS, while mice deficient in Nox3 do not. This suggests 1) a normal utricle is necessary, and 2) functioning semicircular canals are insufficient, to generate MVS-induced nystagmus in mice.

Background Small, innate asymmetries between the left and right otolith organs can cause ocular misalignment with symptoms that include double vision and motion sickness. Additionally, ocular misalignment affects nearly 5% of the US population. We have developed a portable, non-invasive technology that uses subjective perception of binocular visual signals to estimate relative binocular alignment. New method and results The Vertical Alignment Nulling (VAN) and Torsional Alignment Nulling (TAN) tests ask subjects to view one red and one blue line on a tablet computer while looking through color-matched red and blue filters so that each eye sees only one of the lines. Subjects align the red and blue lines, which are initially vertically offset from one another during VAN or rotated relative to one another during TAN, until they perceive a single continuous line. Ocular misalignments are inferred from actual offsets in the final line positions. During testing, all binocular visual cues are eliminated by employing active-matrix organic light-emitting diode (AMOLED) technology and testing in darkness. VAN and TAN can accurately account for visual offsets induced by prisms, and test-retest reliability is excellent, with resolution better than many current standard clinical tests. Comparison with existing method(s) VAN and TAN tests are similar to the clinical Lancaster red-green test. However, VAN and TAN employ inexpensive, hand-held hardware that can be self-administered with results that are quickly quantifiable. Conclusions VAN and TAN provide simple, sensitive, and quantitative measures of binocular positioning alignment that may be useful for detecting subtle abnormalities in ocular positioning.

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.

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.

BACKGROUND: Bilateral loss of vestibular (inner ear inertial) sensation causes chronically blurred vision during head movement, postural instability, and increased fall risk. Individuals who fail to compensate despite rehabilitation therapy have no adequate treatment options. Analogous to hearing restoration via cochlear implants, prosthetic electrical stimulation of vestibular nerve branches to encode head motion has garnered interest as a potential treatment, but prior studies in humans have not included continuous long-term stimulation or 3D binocular vestibulo-ocular reflex (VOR) oculography, without which one cannot determine whether an implant selectively stimulates the implanted ear’s 3 semicircular canals. METHODS: We report binocular 3D VOR responses of 4 human subjects with ototoxic bilateral vestibular loss unilaterally implanted with a Labyrinth Devices Multichannel Vestibular Implant System vestibular implant, which provides continuous, long-term, motion-modulated prosthetic stimulation via electrodes in 3 semicircular canals. RESULTS: Initiation of prosthetic stimulation evoked nystagmus that decayed within 30 minutes. Stimulation targeting 1 canal produced 3D VOR responses approximately aligned with that canal’s anatomic axis. Targeting multiple canals yielded responses aligned with a vector sum of individual responses. Over 350–812 days of continuous 24 h/d use, modulated electrical stimulation produced stable VOR responses that grew with stimulus intensity and aligned approximately with any specified 3D head rotation axis. CONCLUSION: These results demonstrate that a vestibular implant can selectively, continuously, and chronically provide artificial sensory input to all 3 implanted semicircular canals in individuals disabled by bilateral vestibular loss, driving reflexive VOR eye movements that approximately align in 3D with the head motion axis encoded by the implant. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02725463. FUNDING: NIH/National Institute on Deafness and Other Communication Disorders: R01DC013536 and 2T32DC000023; Labyrinth Devices, LLC; and Med-El GmbH.

Recent studies have shown that ionic direct current (iDC) can modulate the vestibular system in-vivo, with potential benefits over conventional pulsed stimulation. In this study, the effects of iDC stimulation on vestibular nerve fiber firing rate was investigated using loose-patch nerve fiber recordings in the acutely excised mouse crista ampullaris of the semicircular canals. Cathodic and anodic iDC steps instantaneously reduced and increased afferent spike rate, with the polarity of this effect dependent on the position of the stimulating electrode. A sustained constant anodic or cathodic current resulted in an adaptation to the stimulus and a return to spontaneous spike rate. Post-adaptation spike rate responses to iDC steps were similar to pre-adaptation controls. At high intensities spike rate response sensitivities were modified by the presence of an adaptation step. Benefits previously observed in behavioral responses to iDC steps delivered after sustained current may be due to post-adaptation changes in afferent sensitivity. These results contribute to an understanding of peripheral spike rate relationships for iDC vestibular stimulation and validate an ex-vivo model for future investigation of cellular mechanisms. In conjunction with previous in-vivo studies, these data help to characterize iDC stimulation as a potential therapy to restore vestibular function after bilateral vestibulopathy.

For many years, people working near strong static magnetic fields of magnetic resonance imaging (MRI) machines have reported dizziness and sensations of vertigo. The discovery a decade ago that a sustained nystagmus can be observed in all humans with an intact labyrinth inside MRI machines led to a possible mechanism: a Lorentz force occurring in the labyrinth from the interactions of normal inner ear ionic currents and the strong static magnetic fields of the MRI machine. Inside an MRI, the Lorentz force acts to induce a constant deflection of the semicircular canal cupula of the superior and lateral semicircular canals. This inner ear stimulation creates a sensation of rotation, and a constant horizontal/torsional nystagmus that can only be observed when visual fixation is removed. Over time, the brain adapts to both the perception of rotation and the nystagmus, with the perception usually diminishing over a few minutes, and the nystagmus persisting at a reduced level for hours. This observation has led to discoveries about how the central vestibular mechanisms adapt to a constant vestibular asymmetry and is a useful model of set-point adaptation or how homeostasis is maintained in response to changes in the internal milieu or the external environment. We review what is known about the effects of stimulation of the vestibular system with high-strength magnetic fields and how the understanding of the mechanism has been refined since it was first proposed. We suggest future ways that magnetic vestibular stimulation might be used to understand vestibular disease and how it might be treated.

Summary A major focus in neurobiology is how the brain adapts its motor behavior to changes in its internal and external environments [1, 2]. Much is known about adaptively optimizing the amplitude and direction of eye and limb movements, for example, but little is known about another essential form of learning, "set-point" adaptation. Set-point adaptation balances tonic activity so that reciprocally acting, agonist and antagonist muscles have a stable platform from which to launch accurate movements. Here, we use the vestibulo-ocular reflex—a simple behavior that stabilizes the position of the eye while the head is moving—to investigate how tonic activity is adapted toward a new set point to prevent eye drift when the head is still [3, 4]. Set-point adaptation was elicited with magneto-hydrodynamic vestibular stimulation (MVS) by placing normal humans in a 7T MRI for 90 min. MVS is ideal for prolonged labyrinthine activation because it mimics constant head acceleration and induces a sustained nystagmus similar to natural vestibular lesions [5, 6]. The MVS-induced nystagmus diminished slowly but incompletely over multiple timescales. We propose a new adaptation hypothesis, using a cascade of imperfect mathematical integrators, that reproduces the response to MVS (and more natural chair rotations), including the gradual decrease in nystagmus as the set point changes over progressively longer time courses. MVS set-point adaptation is a biological model with applications to basic neurophysiological research into all types of movements [7], functional brain imaging [8], and treatment of vestibular and higher-level attentional disorders by introducing new biases to counteract pathological ones [9].

Background: Strong static magnetic fields such as those in an MRI machine can induce sensations of self-motion and nystagmus. The proposed mechanism is a Lorentz force resulting from the interaction between strong static magnetic fields and ionic currents in the inner ear endolymph that causes displacement of the semicircular canal cupulae. Nystagmus persists throughout an individual's exposure to the magnetic field, though its slow-phase velocity partially declines due to adaptation. After leaving the magnetic field an after effect occurs in which the nystagmus and sensations of rotation reverse direction, reflecting the adaptation that occurred while inside the MRI. However, the effects of visual fixation and of head shaking on this early type of vestibular adaptation are unknown. Methods: Three-dimensional infrared video-oculography was performed in six individuals just before, during (5, 20, or 60 min) and after (4, 15, or 20 min) lying supine inside a 7T MRI scanner. Trials began by entering the magnetic field in darkness followed 60 s later, either by light with visual fixation and head still, or by continuous yaw head rotations (2 Hz) in either darkness or light with visual fixation. Subjects were always placed in darkness 10 or 30 s before exiting the bore. In control conditions subjects remained in the dark with the head still for the entire duration. Results: In darkness with head still all subjects developed horizontal nystagmus inside the magnetic field, with slow-phase velocity partially decreasing over time. An after effect followed on exiting the magnet, with nystagmus in the opposite direction. Nystagmus was suppressed during visual fixation; however, after resuming darkness just before exiting the magnet, nystagmus returned with velocity close to the control condition and with a comparable after effect. Similar after effects occurred with continuous yaw head rotations while in the scanner whether in darkness or light. Conclusions: Visual fixation and sustained head shaking either in the dark or with fixation inside a strong static magnetic field have minimal impact on the short-term mechanisms that attempt to null unwanted spontaneous nystagmus when the head is still, so called VOR set-point adaptation. This contrasts with the critical influence of vision and slippage of images on the retina on the dynamic (gain and direction) components of VOR adaptation.

After their introduction by Robinson (IEEE Trans Biomed Eng 10:137-145, 1963), magnetic scleral search coils quickly became an accepted standard for precise eye movement recordings. While other techniques such as video-oculography or electro-oculography may be more suitable for routine applications, search coils still provide the best low-noise and low-drift characteristics paired with the highest temporal and spatial resolution. The problem with search coils is that many research laboratories still have their large and expensive coil systems installed and are acquiring eye movement data with old, analog technology. Typically, the number of recording channels is limited and modifications to an existing search coil system can be difficult. We propose a system that allows to retro-fit an existing analog search coil system to become a digital recording system. The system includes digital data acquisition boards and a reference coil as the hardware part, receiver software, and a new calibration method. The circuit design has been kept simple and robust, and the proposed software calibration allows the calibration of a single coil within a few seconds.

Individuals working next to strong static magnetic fields occasionally report disorientation and vertigo. With the increasing strength of magnetic fields used for magnetic resonance imaging studies, these reports have become more common. It was recently learned that humans, mice, and zebrafish all demonstrate behaviors consistent with constant peripheral vestibular stimulation while inside a strong, static magnetic field. The proposed mechanism for this effect involves a Lorentz force resulting from the interaction of a strong static magnetic field with naturally occurring ionic currents flowing through the inner ear endolymph into vestibular hair cells. The resulting force within the endolymph is strong enough to displace the lateral semicircular canal cupula, inducing vertigo and the horizontal nystagmus seen in normal mice and in humans. This review explores the evidence for interactions of magnetic fields with the vestibular system.

Previous experiments have shown that the vestibulo-ocular reflex (VOR) is partially suppressed during large head-free gaze (gaze = eye-in-head + head-in-space) shifts when both the eyes and head are moving actively, on a fixed body, or when the eyes are moving actively and the head passively on a fixed body. We tested, in human subjects, the hypothesis that the VOR is also suppressed during gaze saccades made withen bloc, head and body together, rotations. Subjects made saccades by following a target light. During some trials, the chair rotated so as to move the entire body passively before, during, or after a saccade. The modulation of the VOR was a function of both saccade amplitude and the time of the head perturbation relative to saccade onset. Despite the perturbation, gaze remained accurate. Thus, VOR modulation is similar when gaze changes are programmed for the eyes alone or for the eyes and head moving together. We propose that the brain always programs a change in gaze using feedback based on gaze and head signals, rather than on separate eye and head trajectories.

Summary 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.

Torsional eye movements are rotations of the eye around the line of sight. Measuring torsion is essential to understanding how the brain controls eye position and how it creates a veridical perception of object orientation in three dimensions. Torsion is also important for diagnosis of many vestibular, neurological, and ophthalmological disorders. Currently, there are multiple devices and methods that produce reliable measurements of horizontal and vertical eye movements. Measuring torsion, however, noninvasively and reliably has been a longstanding challenge, with previous methods lacking real-time capabilities or suffering from intrusive artifacts. We propose a novel method for measuring eye movements in three dimensions using modern computer vision software (OpenCV) and concepts of iris recognition. To measure torsion, we use template matching of the entire iris and automatically account for occlusion of the iris and pupil by the eyelids. The current setup operates binocularly at 100 Hz with noise

OBJECTIVE: To test the effects of a sustained nystagmus on the head impulse response of the vestibulo-ocular reflex (VOR) in healthy subjects. METHODS: VOR gain (slow-phase eye velocity/head velocity) was measured using video-head impulse test (vHIT) goggles. Acting as a surrogate for a spontaneous nystagmus (SN) a post-rotatory nystagmus (PRN) was elicited after a sustained, constant-velocity rotation and then head impulses were applied. RESULTS: ‘Raw’ VOR gain, uncorrected for PRN, in healthy subjects in response to head impulses with peak velocities in the range of 150- 250 deg/s was significantly increased (as reflected in an increase of the slope of the gain versus head velocity relationship) after inducing PRN with slow phases of nystagmus of high intensity (>30deg/s) in the same but not in the opposite direction as the slow-phase response induced by the head impulses. The values of VOR gain themselves, however, remained in the normal range with slow-phase velocities of PRN

Previous studies established that vestibular reflexes can have two adapted states (e.g., gains) simultaneously, and that a context cue (e.g., vertical eye position) can switch between the two states. Our earlier work demonstrated this phenomenon of context-specific adaptation for saccadic eye movements: we asked for gain decrease in one context state and gain increase in another context state, and then determined if a change in the context state would invoke switching between the adapted states. Horizontal and vertical eye position and head orientation could serve, to varying degrees, as cues for switching between two different saccade gains. In the present study, we asked whether gravity magnitude could serve as a context cue: saccade adaptation was performed during parabolic flight, which provides alternating levels of gravitoinertial force (0 g and 1.8 g). Results were less robust than those from ground experiments, but established that different saccade magnitudes could be associated with different gravity levels.

We recently discovered that static magnetic fields from high-strength MRI machines induce nystagmus in all normal humans, and that a magneto-hydrodynamic Lorentz force, derived from ionic currents in the endolymph and pushing on the cupula, best explains this effect. Individuals with no labyrinthine function have no nystagmus. The influence of magnetic vestibular stimulation (MVS) in individuals with unilateral deficits in labyrinthine function is unknown and may provide insight into the mechanism of MVS. These individuals should experience MVS, but with a different pattern of nystagmus consistent with their unilateral deficit in labyrinthine function. We recorded eye movements in the static magnetic field of a 7 T MRI machine in nine individuals with unilateral labyrinthine hypofunction, as determined by head impulse testing and vestibular-evoked myogenic potentials (VEMP). Eye movements were recorded using infrared video-oculography. Static head positions were varied in pitch with the body supine, and slow-phase eye velocity (SPV) was assessed. All subjects exhibited predominantly horizontal nystagmus after entering the magnet head-first, lying supine. The SPV direction reversed when entering feet-first. Pitching chin-to-chest caused subjects to reach a null point for horizontal SPV. Right unilateral vestibular hypofunction (UVH) subjects developed slow-phase-up nystagmus and left UVH subjects, slow-phase-down nystagmus. Vertical and torsional components were consistent with superior semicircular canal excitation or inhibition, respectively, of the intact ear. These findings provide compelling support for the hypothesis that MVS is a result of a Lorentz force and suggest that the function of individual structures within the labyrinth can be assessed with MVS. As a novel method of comfortable and sustained labyrinthine stimulation, MVS can provide new insights into vestibular physiology and pathophysiology.

We study here the effect of a short-term training paradigm on the gain and phase of the human translational VOR (the linear VOR: LVOR). Subjects were exposed to lateral sinusoidal translations on a sled, at 0.5 Hz, 0.3 g peak acceleration. With subjects tracking a remembered target at 1.2 m, the LVOR (slow-phase) under these conditions typically has a phase lead or lag, and a gain that falls short of compensatory. To induce short-term adaptation (training), we presented an earth-fixed visual scene at 1.2 m during sinusoidal translation ( × 1 viewing) for 20 minutes, so as to drive the LVOR toward compensatory phase and gain. We examined both the slow-phase and the saccadic responses to these stimuli. Testing after training showed changes in slow-component gain and phase which were mostly but not always in the compensatory direction. These changes were more consistent in naive subjects than in subjects who had previous LVOR experience. Changes in gain were seen with step as well as sinusoidal test stimuli; gain changes were not correlated with vergence changes. There was a strong correlation between gain changes and phase changes across subjects. Fast phases (catch-up saccades) formed a large component of the LVOR under our testing conditions (approximately 30% of the changes in gain but not in phase due to training.

Fragestellung: Untersucht wurde der Einflus unterschiedlicher konvergenter Augenstellungen auf die vertikale Fusionsbreite. Methodik: 12 Normalpersonen wurde haploskopisch mit einer LCD-Brille ein Kreuz angeboten, das unter einem Gesichtswinkel von 3,4°×3,2° gesehen wurde. Vertikale Disparitat wurde durch Verschiebung eines der beiden Kreuze um 0.08° alle 8 Sekunden nach oben oder nach unten erzeugt. Beim Fernblick betrug die Konvergenzanforderung 1°, beim Nahblick wurden je nach Proband zwischen 6 und 15° Konvergenzanforderung toleriert. Die jeweilige Augenlage wurde mit der Search-Coil-Methode registriert. Ergebnisse: Bei 9 der 12 Probanden war die vertikale Fusionsbreite bei Nahblick groser als bei Fernblick. Fur die Gesamtgruppe zeigte die Gesamtfusion (Summe aus motorischer und sensorischer Fusion) einen signifikanten Unterschied zwischen Fernblick (MW 1,68°) und Nahblick (MW 2,39°). Die motorische Fusionsantwort war bei Nahblick signifikant groser (MW 2,13°) als bei Fernblick (MW 1,42°). Der sensorische Fusionsanteil zeigte keinen Unterschied (Nahblick MW 0,27°, Fernblick MW 0,26°). Schlussfolgerung: Die vertikale Fusionsbreite erhoht sich bei konvergenter Augenstellung durch eine Zunahme des motorischen Anteils an der Fusionsantwort.

Testing of the vestibular system requires a vestibular stimulus (motion) and/or a visual stimulus. We have developed a versatile, low cost, stereoscopic visual display system, using “virtual reality” (VR) technology. The display system can produce images for each eye that correspond to targets at any virtual distance relative to the subject, and so require the appropriate ocular vergence. We elicited smooth pursuit, “stare” optokinetic nystagmus (OKN) and after-nystagmus (OKAN), vergence for targets at various distances, and short-term adaptation of the vestibulo-ocular reflex (VOR), using both conventional methods and the stereoscopic display. Pursuit, OKN, and OKAN were comparable with both methods. When used with a vestibular stimulus, VR induced appropriate adaptive changes of the phase and gain of the angular VOR. In addition, using the VR display system and a human linear acceleration sled, we adapted the phase of the linear VOR. The VR-based stimulus system not only offers an alternative to more cumbersome means of stimulating the visual system in vestibular experiments, it also can produce visual stimuli that would otherwise be impractical or impossible. Our techniques provide images without the latencies encountered in most VR systems. Its inherent versatility allows it to be useful in several different types of experiments, and because it is software driven it can be quickly adapted to provide a new stimulus. These two factors allow VR to provide considerable savings in time and money, as well as flexibility in developing experimental paradigms.

Zebrafish (Danio rerio) offer advantages as model animals for studies of inner ear development, genetics and ototoxicity. However, traditional assessment of vestibular function in this species using the vestibulo-ocular reflex requires agar-immobilization of individual fish and specialized video, which are difficult and labor-intensive. We report that using a static magnetic field to directly stimulate the zebrafish labyrinth results in an efficient, quantitative behavioral assay in free-swimming fish. We recently observed that humans have sustained nystagmus in high strength magnetic fields, and we attributed this observation to magnetohydrodynamic forces acting on the labyrinths. Here, fish were individually introduced into the center of a vertical 11.7T magnetic field bore for 2-minute intervals, and their movements were tracked. To assess for heading preference relative to a magnetic field, fish were also placed in a horizontally oriented 4.7T magnet in infrared (IR) light. A sub-population was tested again in the magnet after gentamicin bath to ablate lateral line hair cell function. Free-swimming adult zebrafish exhibited markedly altered swimming behavior while in strong static magnetic fields, independent of vision or lateral line function. Two-thirds of fish showed increased swimming velocity or consistent looping/rolling behavior throughout exposure to a strong, vertically oriented magnetic field. Fish also demonstrated altered swimming behavior in a strong horizontally oriented field, demonstrating in most cases preferred swimming direction with respect to the field. These findings could be adapted for ‘high-throughput’ investigations of the effects of environmental manipulations as well as for changes that occur during development on vestibular function in zebrafish.

Objective: Development of an easy to administer, low-cost test of vestibular function. Methods: Members of the NIH Toolbox Sensory Domain Vestibular, Vision, and Motor subdomain teams collaborated to identify 2 tests: 1) Dynamic Visual Acuity (DVA), and 2) the Balance Accelerometry Measure (BAM). Extensive work was completed to identify and develop appropriate software and hardware. More than 300 subjects between the ages of 3 and 85 years, with and without vestibular dysfunction, were recruited and tested. Currently accepted gold standard measures of static visual acuity, vestibular function, dynamic visual acuity, and balance were performed to determine validity. Repeat testing was performed to examine reliability. Results: The DVA and BAM tests are affordable and appropriate for use for individuals 3 through 85 years of age. The DVA had fair to good reliability (0.41–0.94) and sensitivity and specificity (50%–73%), depending on age and optotype chosen. The BAM test was moderately correlated with center of pressure (r 5 0.42–0.48) and dynamic posturography (r 52 0.48), depending on age and test condition. Both tests differentiated those with and without vestibular impairment and the young from the old. Each test was reliable. Conclusion: The newly created DVA test provides a valid measure of visual acuity with the head still and moving quickly. The novel BAM is a valid measure of balance. Both tests are sensitive to age-related changes and are able to screen for impairment of the vestibular system. Neurology

Publisher Summary This chapter reviews search coil systems for eye-movement measurement. It discusses that as knowledge of vestibular and oculomotor function increases, there is an associated requirement for highly accurate and precise measurements of the movements of the eyes. Scleral search coil systems represent the current “gold standard” for measurement of the eye movements. Other eye movement recording methods may be superior to the search coil system in specific aspects, but to date no other method matches the combined resolution, accuracy, low noise, fast response, wide range, cost effectiveness, and ease of use of the search coil system. Thus, this method is likely to remain in wide use for many years. The chapter discusses that there are many variations on the search coil system. They may use anywhere from one to three generated magnetic fields, and one or two coils in the eye. Using a single coil in the eye with its plane perpendicular to the line of sight, it is possible to deduce the direction of gaze. With a second coil perpendicular to the first, it is possible to deduce the amount of torsional rotation about the line of sight. It concludes that despite the difficulties noted below, the method has even been used in the demanding environment of “weightless” parabolic flight.

The three pairs of semicircular canals within the labyrinth are not perfectly aligned with the pulling directions of the six extraocular muscles. Therefore, for a given head movement, the vestibulo-ocular reflex (VOR) depends upon central neural mechanisms that couple the canals to the muscles with the appropriate functional gains in order to generate a response that rotates the eye the correct amount and around the correct axis. A consequence of these neural connections is a cross-axis adaptive capability, which can be stimulated experimentally when head rotation is around one axis and visual motion about another. From this visual-vestibular conflict the brain infers that the slow-phase eye movement is rotating around the wrong axis. We explored the capability of human cross-axis adaptation, using a short-term training paradigm, to determine if torsional eye movements could be elicited by yaw (horizontal) head rotation (where torsion is normally inappropriate). We applied yaw sinusoidal head rotation (+/-10 degrees, 0.33 Hz) and measured eye movement responses in the dark, and before and after adaptation. The adaptation paradigm lasted 45-60 min, and consisted of the identical head motion, coupled with a moving visual scene that required one of several types of eye movements: (1) torsion alone (-Roll); (2) horizontal/torsional, head right/CW torsion (Yaw-Roll); (3) horizontal/torsional, head right/CCW torsion (Yaw+Roll); (4) horizontal, vertical, torsional combined (Yaw+Pitch-Roll); and (5) horizontal and vertical together (Yaw+Pitch). The largest and most significant changes in torsional amplitude occurred in the Yaw-Roll and Yaw+Roll conditions. We conclude that short-term, cross-axis adaptation of torsion is possible but constrained by the complexity of the adaptation task: smaller torsional components are produced if more than one cross-coupling component is required. In contrast, vertical cross-axis components can be easily trained to occur with yaw head movements.

INTRODUCTION The goal of the National Institutes of Health (NIH) Toolbox initiative is to develop a valid set of instruments that measure motor, sensory, cognitive, and emotive functions for large-scale epidemiological and clinical trials and studies in subjects aged 3 to 85 years [1]. An important mandate of this goal was to develop instruments that could be administered with minimal training by nonclinical persons. For the sensory domain, a joint effort was invested by the vestibular and vision function teams to develop a single tool that would be useful for testing both senses. A select group of clinicians and basic scientists served on separate vestibular and vision teams to identify appropriate tests for their respective sensory area, followed by joint meetings to identify areas of testing overlap between the two teams. The documentation of an increasing need for tests that can identify vestibular and/or visual impairments throughout the lifespan supports the development of tools to meet that need. The vestibular system is an integral component of human sensory perception, including the perception of angular and linear motion. It provides the brain with both sensory afference and motor efference. Putative vestibular impairments affect 35 percent of U.S. adults over 40 years old [2], with approximately 8 million U.S. adults reporting chronic balance problems [3]. Aside from imbalance, consequences of vestibular deficits also include gaze instability and increased risk for falls [4]. Similar problems exist in pediatric populations. Recently, O'Reilly et al. completed a review of pediatric patients seen over a 4-year period with a chief complaint of dizziness or imbalance [5]. Of those seen by specialists in otolaryngology, 35 percent had confirmed vestibular disorders. Casselbrant et al. reported that balance and vestibular problems persist in children with a history of chronic middle ear effusion after the resolution of the effusion [6]. Together, growing evidence suggests that a significant percentage of adults and children have vestibular deficits, and the incidence in children is underestimated [7-8]. Part of the challenge in identifying the population with vestibular hypofunction (VH) is the existence of a significant time delay from the onset of symptoms to appropriate referral. This is in part caused by the lack of screening tools that can be used by nonspecialists to identify those individuals who should be referred for specialized testing and treatment. Vision is a complex sensation that provides a personal representation of an individual's surrounding environment. With the aging of the U.S. population, evaluation and treatment of age-related changes in vision-related diseases will be of growing importance in the next several decades. It is estimated that more than 150 million people in the U.S. general population wear corrective lenses to compensate for visual impairment caused by refractive error [9], which may include myopia, hyperopia, astigmatism, and presbyopia. Other relatively common disease-related causes of visual impairment include age-related macular degeneration, cataracts, diabetic retinopathy, and glaucoma. Studies to prevent and evaluate treatment for these conditions will be of increasing value because the number of people with vision impairment from age-related eye disease is expected to double in the next three decades [9]. Both the vestibular and vision teams were given the task of developing a test that was (1) limited in number of tests and/or demands on the study participants, (2) inexpensive, (3) time efficient, (4) portable, (5) a valid indicator of gaze stability and vision acuity, (6) able to be performed in subjects aged 3 to 85 years, and (7) capable of automated scoring and storing of data. The exclusion criteria for tests to be selected were (1) reliance on self-report of symptoms, (2) high cost, (3) requirement of examiner expertise, or (4) lack of psychometric strength (i. …

We investigated the effect of short-term vestibulo-ocular reflex (VOR) adaptation in normal human subjects on the dynamic properties of the velocity-to-position ocular motor integrator that holds positions of gaze. Subjects sat in a sinusoidally rotating chair surrounded by an optokinetic nystagmus drum. The movement of the visual surround (drum) was manipulated relative to the chair to produce an increase (x 1.7 viewing), decrease (x 0.5, x 0 viewing), or reversal (x (-2.5) viewing) of VOR gain. Before and after 1 h of training, VOR gain and gaze-holding after eccentric saccades in darkness were measured. Depending on the training paradigm, eccentric saccades could be followed by centrifugal drift (after x 0.5 viewing), implying an unstable integrator, or by centripetal drift [after x 1.7 or x (-2.5) viewing], implying a leaky integrator. The changes in the neural integrator appear to be context specific, so that when the VOR was tested in non-training head orientations, both the adaptive change in VOR gain and the changes in the neural integrator were much smaller. The changes in VOR gain were on the order of 10% and the induced drift velocities were several degrees per second at 20 deg eccentric positions in the orbit. We propose that (1) the changes in the dynamic properties of the neural integrator reflect an attempt to modify the phase (timing) relationships of the VOR and (2) the relative directions of retinal slip and eye velocity during head rotation determine whether the integrator becomes unstable (and introduces more phase lag) or leaky (and introduces less phase lag).

We oscillated humans sinusoidally at 0.2 Hz for 1 h, using various combinations of rotations of the head and visual surround to elicit short-term adaptation of the gain of the vestibulo-ocular reflex (VOR). Before and after each period of training, the gain of the VOR was measured in darkness, in response to a position step of head rotation. A small foveal target served as well as a full-field stimulus at driving VOR adaptation. Oscillation of the visual surround alone produced a substantial increase in the VOR gain. When the visual scene was rotated in phase with the head but with a larger amplitude to produce a reversal of the VOR, the VOR gain increased if the movement of the visual scene was much greater than that of the head, otherwise the gain decreased. We interpreted these results with a model of VOR adaptation that uses as its "error signal" the combination of motion of images on the retina (retinal slip) and any additional slow-phase eye velocity, beyond that generated by the VOR through the vestibular nuclei, necessary to prevent such retinal slip during head rotation. The slow phase velocity generated by the VOR is derived from "inferred head rotation", a signal based on the discharge of neurons in the vestibular nuclei that receive both labyrinthine and visual (optokinetic) inputs. The amplitude and sign of the ratio of the "error signal" to "inferred head velocity" determined the amplitude and the direction (increase or decrease) of VOR gain adaptation.