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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.

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.

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].

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.

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

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.

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

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.