Dale C. Roberts

Transient torsion during and after saccades.

In five normal subjects, we analyzed uncalled for torsion (blips) during and after horizontal and vertical saccades. Torsion was defined as movement out of Listings plane. During horizontal saccades in downward gaze the abducting eye extorted and the adducting eye intorted. The direction of the blips reversed in upward gaze. Peak torsional amplitudes (up to 1-2 deg) were always reached during saccades; drifts back to Listings plane outlasted the saccades. Torsion of the extorting eye was larger than that of the intorting eye, producing a transient positive cyclovergence. Torsion and cyclovergence evoked by vertical saccades were also stereotyped in each eye, but showed idiosyncratic differences among subjects. We conclude that Listings law is violated during saccades. Transient saccade-evoked torsion might reflect properties of the three-dimensional velocity-to-position integrator and/or the ocular plant.

MRI Magnetic Field Stimulates Rotational Sensors of the Brain

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 cupulas 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.

Short-term vestibulo-ocular reflex adaptation in humans - I. Effect on the ocular motor velocity-to-position neural integrator

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 (× 1.7 viewing), decrease (× 0.5, × 0 viewing), or reversal (× (-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 × 0.5 viewing), implying an unstable integrator, or by centripetal drift [after × 1.7 or × (-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 secend 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).

Short-term vestibulo-ocular reflex adaptation in humans. II. Error signals.

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” determine the amplitude and the direction (increase or decrease) of VOR gain adaptation.

Vestibular function assessment using the NIH Toolbox

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 = 0.42–0.48) and dynamic posturography (r = −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.

Magnetic Vestibular Stimulation in Subjects with Unilateral Labyrinthine Disorders

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.

New portable tool to screen vestibular and visual function—National Institutes of Health Toolbox initiative

As part of the National Institutes of Health Toolbox initiative, we developed a low-cost, easy-to-administer, and time-efficient test of vestibular and visual function. A computerized test of dynamic visual acuity (cDVA) was used to measure the difference in visual acuity between head still and moving in yaw. Participants included 318 individuals, aged 3 to 85 years (301 without and 17 with vestibular pathology). Adults used Early Treatment of Diabetic Retinopathy Study (ETDRS) optotypes; children used ETDRS, Lea, and HOTV optotypes. Bithermal calorics, rotational chair, and light box testing were used to validate the cDVA. Analysis revealed that the cDVA test is reliable for static (intraclass correlation coefficient [ICC] >/= 0.64) and dynamic (ICC >/= 0.43-0.75) visual acuity. Children younger than 6 years old were more likely to complete cDVA with Lea optotypes, but reliability and correlation with ETDRS was better using HOTV optotypes. The high correlation between static acuity and light box test scores (r = 0.795), significant difference of cDVA scores between those with and without pathology (p </= 0.04), and the good to excellent sensitivity (73%) and specificity (69%) establish that the cDVA is a valid and reliable measure of visual acuity when the head is still and moving, as well as a good proxy of vestibular function to yaw rotation.

A new "wireless" search-coil system

The scleral search-coil system is the accepted standard for precise and accurate recording of eye movements in the lab and clinic. One of the drawbacks of this system is the connecting wire that leads from the eye coil to the associated electronics; this wire causes irritation to the subject and has a tendency to break during experiments. We have developed a modified version of this technique, which uses a resonant scleral coil and no connecting wire. A transmitter sends a stream of pulses to the eye coil, and a receiver then detects the resonant oscillations re-radiated from the eye coil. The relative intensity of the signal as received by sets of orthogonal receiver coils determines the orientation of the eye coil. The new approach retains the advantages of accuracy, precision, and high sample rate, while making the system portable and more comfortable.

Strong Static Magnetic Fields Elicit Swimming Behaviors Consistent with Direct Vestibular Stimulation in Adult Zebrafish

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.

Vestibular stimulation by magnetic fields

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.