Stabilization of the gaze in chameleons: visual and vestibular reflexes

Some visual, vestibular and proprioceptive reflexes which contribute to gaze (head + eye) stabilization were quantified in the chameleon. All the reflexes were analysed in the horizontal plane, and the visual reflexes were also studied in the vertical plane. In restrained-head animals, both the optokinetic nystagmus (OKN) and the vestibulo-ocular reflex (VOR) had low gains. In free-head animals, the head (opto-collic or vestibulo-collic reflex) and eye (OKN or VOR) responses added their effects, thus improving gaze stabilization, especially during vestibular stimulation. Cervical stimulation provoked both a cervico-ocular reflex (COR) in the compensatory direction and a large number of saccades. The saccadic response was especially marked in the presence of patterned visual surroundings.     

Elasmobranch eye motor dynamics characterised using pseudorandom stimulus

A pseudorandom binary sequence electrical pulse rate stimulus was delivered to the abducens nerve of an elasmobranch preparation. Ipsilateral eye movements were recorded using a position-sensitive photodiode to measure the position of a reflective patch attached to the fish's eye. Eye position data was cross-correlated with the stimulus pattern, and exponential decay curves were fitted to the cross-correlograms to estimate the time constant of a linear first order low-pass filter model. The cross-correlograms were transformed into the frequency domain using a Digital Fourier Transform, and Bode plots of eye dynamics were plotted. Eye motor plant dynamics in the elasmobranch Cephaloscyllium isabella can be accurately characterised by a linear first order low-pass filter model with a corner frequency of 0.73 +/- 0.10 Hz. Non-minimum phase lag reaches 90 degrees at about 4 Hz, indicating a time delay of some 50-60 ms. Integration of the canal signal is not required for producing compensatory eye movements above the characteristic frequency of the eye motor plant. However, the canal signal may be integrated to ensure that the vestibulo-ocular reflex is compensatory at lower frequencies. Substantial phase compensation or prediction is required for effective control of the vestibulo-ocular reflex.     

High-Speed Video-Oculography for Measuring Three-Dimensional Rotation Vectors of Eye Movements in Mice

Background

The mouse is the most commonly used animal model in biomedical research because of recent advances in molecular genetic techniques. Studies related to eye movement in mice are common in fields such as ophthalmology relating to vision, neuro-otology relating to the vestibulo-ocular reflex (VOR), neurology relating to the cerebellum’s role in movement, and psychology relating to attention. Recording eye movements in mice, however, is technically difficult.

Methods

We developed a new algorithm for analyzing the three-dimensional (3D) rotation vector of eye movement in mice using high-speed video-oculography (VOG). The algorithm made it possible to analyze the gain and phase of VOR using the eye’s angular velocity around the axis of eye rotation.

Results

When mice were rotated at 0.5 Hz and 2.5 Hz around the earth’s vertical axis with their heads in a 30° nose-down position, the vertical components of their left eye movements were in phase with the horizontal components. The VOR gain was 0.42 at 0.5 Hz and 0.74 at 2.5 Hz, and the phase lead of the eye movement against the turntable was 16.1° at 0.5 Hz and 4.88° at 2.5 Hz.

Conclusions

To the best of our knowledge, this is the first report of this algorithm being used to calculate a 3D rotation vector of eye movement in mice using high-speed VOG. We developed a technique for analyzing the 3D rotation vector of eye movements in mice with a high-speed infrared CCD camera. We concluded that the technique is suitable for analyzing eye movements in mice. We also include a C++ source code that can calculate the 3D rotation vectors of the eye position from two-dimensional coordinates of the pupil and the iris freckle in the image to this article.     

Cross axis VOR induced by pursuit training in monkeys: further properties of adaptive responses

We have shown recently in alert monkeys that repeated interaction between the pursuit and vestibular systems in the orthogonal plane induces adaptive changes in the VOR. To examine further properties of adaptive cross axis VOR induced by pursuit training, sinusoidal whole body rotation was applied either in the pitch or yaw plane while presenting a target spot that moved orthogonally to the rotation plane with either 90 degrees phase-lead or 90 degrees phase-lag to the chair signal. After one hour of training at 0.5 Hz (+/- 10 degrees), considerable phase-shift was observed in orthogonal eye movement responses consistent with the training paradigms by identical chair rotation in complete darkness, with further lead at lower frequencies and lag at higher frequencies. However, gains (eye/chair) induced by phase- shift pursuit training was different during pitch and yaw rotation. Although frequency tuning was maintained during pitch in the phase-shift paradigms, it was not maintained during yaw, resulting in higher gains at lower stimulus frequencies compared to the gains during yaw. This difference may reflect otolith contribution during pitch rotation. To understand further the nature of signals that induce adaptive cross axis VOR, we examined interaction of pursuit, whole field-visual pattern and vestibular stimuli. Magnitudes of the cross axis VOR with a spot alone on one hand and with a spot and pattern moving together in the same plane on the other during chair rotation were similar, and when one of the two visual stimuli was stationary during chair rotation, our well trained monkeys did not induce the cross axis VOR. These results suggest that the cross axis VOR induced by pursuit training shares common mechanisms with the cross axis VOR induced by whole field-slip stimuli and that if conflicting information is given between the two visual stimuli, adaptive changes are inhibited. Horizontal GVPs were recorded in the cerebellar floccular lobe during pitch rotation coupled with horizontal pursuit stimuli. These GVPs did not respond to pitch in the dark before training, but responded after 60 min of pursuit training with eye velocity sensitivities similar to those before training. Adaptive change in the VOR was specific to smooth eye movements but not to saccades in our paradigms.     

Tuning of the ocular vestibular evoked myogenic potential to bone-conducted sound stimulation

Ocular vestibular evoked myogenic potentials (oVEMPs) are a recently described clinical measure of the vestibulo-ocular reflex. Studies demonstrating differences in frequency tuning between air-conducted and bone-conducted (BC) oVEMPs suggest a separate vestibular (otolith) origin for each stimulus modality. In this study, 10 healthy subjects were stimulated with BC stimuli using a hand-held minishaker. Frequencies were tested in the range of 50-1,000 Hz using both a constant-force and constant-acceleration method. Subjects were stimulated at the mastoid process and the forehead. For constant-force stimulation at both sites, maximum acceleration occurred around 100 Hz, in differing axes. Both forms of stimulation had low-frequency peaks of oVEMP amplitudes (constant force: mastoid, 80-150 Hz; forehead, 50-125 Hz; constant acceleration: mastoid, 100-200 Hz; forehead, 80-150 Hz), for both sites of application, despite differences in the magnitude and direction of evoked head acceleration. For mastoid stimulation, ocular responses changed from out of phase to in phase for 400 Hz and above. Our results demonstrate that BC stimuli show tuning around 100 Hz, independent of stimulus site, that is not due to skull properties. The findings are consistent with an effect on a receptor with a resonance around 100 Hz, most likely the utricle.     

The use of matrices in analyzing the three-dimensional behavior of the vestibulo-ocular reflex

The vestibulo-ocular reflex rotates the eye about the axis of a head rotation at the same speed but in the opposite direction to make the visual axes in space independent of head motion. This reflex works in all three degrees of freedom: roll, pitch, and yaw. The rotations may be described by vectors and the reflex by a transformation in the form of a matrix. The reflex consists of three parts: sensory, central, and motor. The transduction of head rotation into three neural signals, which may also be described by a vector, is described by a canal matrix. The neural, motorcommand vector is transformed to an eye rotation by a muscle matrix. Since these two matrices are known, one can solve for the central matrix which gives the strength of the connections between all the vestibular neurons and all the eye-muscle motoneurons. The role of the metric tensor in these transformations is described. This method of analysis is used in three applications. A lesion may be simulated by altering the elements in any or all of the three component matrices. By matrix multiplication, the resulting abnormal behavior of the reflex can be described quantitatively in all degrees of freedom. The method is also used to directly compare the differences in brain-stem connections between humans and rabbits that accommodate the altered actions of the muscles of the two species. Finally the method allows a quantitative assessment of the changes that take place in the brainstem connections when plastic changes are induced by artificially dissociating head movements from apparent motion of the visual environment.     

Sensitivity of the knee joint kinematics calculation to selection of flexion axes

Various flexion axes have been used in the literature to describe knee joint kinematics. This study measured the passive knee kinematics of six cadaveric human knee specimens using two widely accepted flexion axes; transepicondylar axis and the geometric center axis. These two axes were found to form an angle of 4.0 degrees +/- 0.8 degrees. The tibial rotation calculated using the transepicondylar axis was significantly different than the rotation obtained using the geometric center axis for the same knee motion. At 90 degrees of flexion, the tibial rotation obtained using the transepicondylar axis was 4.8 degrees +/- 9.4 degrees whereas the rotation recorded using the geometric center axis at the same flexion angle was 13.8 degrees +/- 10.2 degrees. At 150 degrees of knee flexion, the rotations obtained from the transepicondylar and the geometric center axes were 7.2 degrees +/- 5.7 degrees and 19.9 degrees +/- 6.9 degrees, respectively. The data suggest that a clear definition of the flexion axis is necessary when reporting knee joint kinematics.     

Application of linear system analysis to the horizontal vestibulo-ocular reflex of the alert rhesus monkey using pseudorandom binary sequence and single frequency sinusoidal stimulation

Horizontal eye movements of the alert rhesus monkey resulting from both pseudorandom binary sequence (PRBS) and single frequency sinusoidal rotational stimulation were analyzed using a PDP 11/40 computer in order to generate gain, phase, and coherence estimates at discrete frequencies between 0.008 and 1.28 Hz. A computer simulation of vestibular induced eye movements was used to validate our analysis procedures and to determine the effects of digital noise. Frequency domain transfer functions derived from gain and phase estimates revealed that the responses to PRBS stimulation and to single frequency sinusoids were not appreciably different. PRBS testing was accomplished in approximately one third the time required for sinusoidal testing and yielded highly reproducible data. We conclude that PRBS stimulation is a reliable and efficient method for assessing linear system parameters of the horizontal vestibulo-ocular reflex. PRBS testing may be particularly and advantageous in studies of vestibulo-oculomotor plasticity in which rapid assessment of alterations in system dynamics is essential.     

Reading from a Head-Fixed Display during Walking: Adverse Effects of Gaze Stabilization Mechanisms

Reading performance during standing and walking was assessed for information presented on earth-fixed and head-fixed displays by determining the minimal duration during which a numerical time stimulus needed to be presented for 50% correct naming answers. Reading from the earth-fixed display was comparable during standing and walking, with optimal performance being attained for visual character sizes in the range of 0.2° to 1°. Reading from the head-fixed display was impaired for small (0.2-0.3°) and large (5°) visual character sizes, especially during walking. Analysis of head and eye movements demonstrated that retinal slip was larger during walking than during standing, but remained within the functional acuity range when reading from the earth-fixed display. The detrimental effects on performance of reading from the head-fixed display during walking could be attributed to loss of acuity resulting from large retinal slip. Because walking activated the angular vestibulo-ocular reflex, the resulting compensatory eye movements acted to stabilize gaze on the information presented on the earth-fixed display but destabilized gaze from the information presented on the head-fixed display. We conclude that the gaze stabilization mechanisms that normally allow visual performance to be maintained during physical activity adversely affect reading performance when the information is presented on a display attached to the head.     

Gravity-dependent and gravity-independent gain changes during vertical vestibulo-ocular reflex (VOR) adaptation

The gain of the vertical angular vestibulo-ocular reflex (aVOR) was adaptively increased or decreased with monkeys in a side down position, and the gains were tested with the axis of rotation tilted in 10 degrees increments from left- to right-side-down. Gain changes, expressed as a percentage of the preadapted values, were plotted as a function of head tilt, and fit with a cosine function. The amplitude of the cosine was half of the gravity-dependent component of the gain change and the bias, the gravity independent component. The largest changes in the gain of both components occurred in the first 30 min and continued at a slower rate throughout adaptation. The gravity-dependent and -independent gain changes were larger for gain decreases than for gain increases, but both components had similar dynamics. We conclude that the alteration in gain of the aVOR always occurs in the context of gravity.     

A linear canal-otolith interaction model to describe the human vestibulo-ocular reflex

A control systems model of the vestibulo-ocular reflex (VOR) originally derived for yaw rotation about an eccentric axis (Crane et al. 1997) was applied to data collected during ambulation and dynamic posturography. The model incorporates a linear summation of an otolith response due to head translation scaled by target distance, adding to a semi-circular canal response that depends only on angular head rotation. The results of the model were compared with human experimental data by supplying head angular velocity as determined by magnetic search coil recording as the input for the canal branch of the model and supplying linear acceleration as determined by flux gate magnetometer measurements of otolith position. The model was fit to data by determining otolith weighting that enabled the model to best fit the data. We fit to the model experimental data from normal subjects who were: standing quietly, walking, running, or making active sinusoidal head movements. We also fit data obtained during dynamic posturography tasks of: standing on a platform sliding in a horizontal plane at 0.2 Hz, standing directly on a platform tilting at 0.1 Hz, and standing on the tilting platform buffered by a 5-cm thick foam rubber cushion. Each task was done with the subject attending a target approximately 500, 100, or 50 cm distant, both in light and darkness. The model accurately predicted the observed VOR response during each test. Greater otolith weighting was required for near targets for nearly all activities, consistent with weights for the otolith component found in previous studies employing imposed rotations. The only exceptions were for vertical axis motion during standing, sliding, and tilting when the platform was buffered with foam rubber. In the horizontal axis, the model always fit near target data better with a higher otolith component. Otolith weights were similar with the target visible and in darkness. The model predicts eye movement during both passive whole-body rotation and free head movement in space implying that the VOR is controlled by a similar mechanism during both situations. Factors such as vision, proprioception, and efference copy that are available during head free motion but not during whole-body rotation are probably not important to gaze stabilization during ambulation and postural stabilizing movement. The linearity of the canal-otolith interaction was tested by re-analysis of the whole body rotation data on which the model is based (Crane et al. 1997). Normalized otolith-mediated gain enhancement was determined for each axis of rotation. This analysis uncovered minor non-linearities in the canal-otolith interaction at frequencies above 1.6 Hz and when the axis of rotation was posterior to the head. Received: 11 March 1998 / Received in revised form: 1 March 1999     

Eye movements and brainstem neuronal responses evoked by cerebellar and vestibular stimulation in chicks

Summary The vestibulo-ocular reflex undergoes adaptive changes that require inputs from the cerebellar flocculus onto brainstem vestibular neurons. As a step toward developing an in vitro preparation in chicks for studying the synaptic basis of those changes, we have elucidated the organization of the pathways through which the flocculus influences vestibulo-ocular movements. Electrical stimulation of the vestibular ampulla evoked brief, contralaterally directed movements in both eyes. Although single current pulses to the flocculus elicited no response, conjunctive stimulation of the flocculus and the vestibular apparatus significantly reduced the vestibularly-evoked movement. Trains of current pulses applied to the flocculus and ampulla evoked eye movements directed toward and away from the side of stimulation, respectively. Recordings from the brainstem revealed neurons that were activated by ipsilateral vestibular stimulation and inhibited by ipsilateral floccular stimulation. Our sample included neurons in the lateral vestibular nucleus, the ventrolateral portion of the medial vestibular nucleus, and the superior vestibular nucleus. Similarities between these findings and those of similar studies in mammals indicate that the chick will provide a good model system for cellular studies of adaptive changes in the vestibulo-ocular reflex.Abbreviations FTN flocculus target neuron - VOR vestibuloocular reflex     

4-Aminopyridine Does Not Enhance Flocculus Function in Tottering,a Mouse Model of Vestibulocerebellar Dysfunction and Ataxia

The potassium channel antagonist 4-aminopyridine (4-AP) improves a variety of motor abnormalities associated with disorders of the cerebellum. The most rigorous quantitative data relate to 4-AP''s ability to improve eye movement deficits in humans referable to dysfunction of the cerebellar flocculus. Largely based on work in the ataxic mouse mutant tottering (which carries a mutation of the Cacna1a gene of the P/Q voltage-activated calcium channel), 4-AP is hypothesized to function by enhancing excitability or rhythmicity of floccular Purkinje cells. We tested this hypothesis by determining whether systemic or intrafloccular administration of 4-AP would ameliorate the eye movement deficits in tottering that are attributable to flocculus dysfunction, including the reductions in amplitude of the yaw-axis vestibulo-ocular reflex (VOR) and vision-enhanced vestibulo-ocular reflex (VVOR), and the optokinetic reflex (OKR) about yaw and roll axes. Because tottering''s deficits increase with age, both young and elderly mutants were tested to detect any age-dependent 4-AP effects. 4-AP failed to improve VOR, VVOR, and OKR gains during sinusoidal stimuli, although it may have reduced the tendency of the mutants'' responses to VOR and VVOR to decline over the course of a one-hour recording session. For constant-velocity optokinetic stimuli, 4-AP generated some enhancement of yaw OKR and upward-directed roll OKR, but the effects were also seen in normal C57BL/6 controls, and thus do not represent a specific reversal of the electrophysiological consequences of the tottering mutation. Data support a possible extra-floccular locus for the effects of 4-AP on habituation and roll OKR. Unilateral intrafloccular 4-AP injections did not affect ocular motility, except to generate mild eye elevations, consistent with reduced floccular output. Because 4-AP did not produce the effects expected if it normalized outputs of floccular Purkinje cells, there is a need for further studies to elucidate the drug''s mechanism of action on cerebellar motor dysfunction.     

Visual position stabilization in the hummingbird hawk moth, Macroglossum stellatarum L. II. Electrophysiological analysis of neurons sensitive to wide-field image motion

Response properties of neurons in the cervical connectives of the hummingbird hawk moth, Macroglossum stellatarum L., were determined. All neurons described in this account respond directionally selectively to motion in large parts of the visual field of either eye. They respond maximally to bilateral stimulation, preferring either motion as induced on the eyes during translatory movements of the animal or when it turns around one of its body axes. Cells most sensitive to rotational motion either respond best to rotation of the patterns around the vertical axis of the animal or around its longitudinal body axis. Neurons most sensitive to translational pattern motion respond best to either simulated translations of the animal along its vertical or along an oblique axis. Most types of neurons respond tonically and do not habituate. The sensitivity to motion stimuli is not evenly distributed within the receptive field of any investigated neuron. Part of these neurons might play a role in visual position and course stabilization. Accepted: 13 August 1997     

The flicker fusion frequencies of six laboratory insects, and the response of the compound eye to mains fluorescent 'ripple'

ABSTRACT. The ERG response of the compound eye to single, brief, light pulses, to sustained stimulation for 2 s, and the dark adapted flicker-fusion frequency (FFF) under stroboscopic light was measured in six species: Locusta migratoria (FFF range: 40–90 Hz), Periplaneta americana (25–60 Hz), Saturnia pavonia (65–85 Hz), Antheraea pernyi (25–70 Hz), Glossina morsitans (85–205 Hz) and Drosophila hydei (60–100 Hz). The first four species have typical 'slow-eyed', monophasic ERG responses; the two flies typical 'fast-eyed', biphasic responses. The FFF proved to be dependent on the state of light adaptation, being 40–70% higher than the above figures after only 2 min exposure to as little as 300 lx. Adult male Glossina , but not Locusta nymphs, showed a clear 100 Hz ERG ripple in response to single-phase, mains fluorescent lighting. To three-phase fluorescent lighting no 300 Hz ERG ripple was detected, but the 100 Hz component was still evident.     

Alterations in rat horizontal vestibulo-ocular reflex phase as a function of orientation in gravity

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

Visual control of steering in locust flight: the effects of head movement on responses to roll stimuli

The contribution of head movement to the control of roll responses in flying locusts (Locusta migratoria) has been examined (i) on a flight balance, recording the angles through which the locust turns when following an artificial horizon; (ii) by recording activity in a pair of flight muscles in restrained conditions; and (iii) by observations on free flying locusts. Responses were compared when the head was free to turn about the thorax, as normal, and when the head was waxed to the thorax, blocking any relative motion between the two (head-fixed). These experiments suggest that the major signal generating corrective roll manoeuvres is the visual error between the angle of the head and the horizon, rather than a signal that includes a measure of the head-thorax angle.

Postnatal development of static vestibulo-ocular reactions in the rabbit--electromyographic studies

The changes in the electric activity of the extraocular muscles as a consequence of static tilt stimulation were investigated in rabbits of different postnatal ages by the registration of the electromyogram. The postnatal development of the tonic vestibulo-ocular reflex in the rabbit runs parallel with the transition from an irregular fluctuating eye muscle activity during the first postnatal days to a constantly tonic muscle activity depending on the tilt position.     

The effect of otolith and semicircular canal convergence on the VOR during eccentric rotation

VOR gain modulation was systematically investigated in the Rhesus monkey (M. mulatta) during centric and variable eccentric (up to 50 cm) sinusoidal rotation (4 Hz, 0.75 degree) with the nose facing in- or outward to test convergence of otolith and semicircular canal afferences. Earth-stationary lit LED-targets were placed at different distances (12-180 cm) from the monkey. Results were compared to biological demands. During centric rotation at 4 Hz when smooth pursuit mechanisms do not play a role, VOR gain--as expected--was approximately 1 without dependence on target distance. Phase of VOR and centrifuge were shifted by about 180 degrees as was predicted. If the monkey was rotated eccentrically with the nose facing outward the expected gain enhancement for close targets was obtained. Maximal experimental VOR gain during 4 Hz rotation was 4.4 which was close to demand at 50 cm eccentricity and 15 cm target distance (predicted gain: 4.6). If the nose points inward three situations have to be distinguished from simulation: (1) target behind the axis of rotation--VOR gain decrement should occur; (2) target on the axis of rotation--"inverse VOR suppression"; (3) target between monkey and axis of rotation--phase reversal. Experimentally, VOR gain decrement was obtained (situation 1). VOR gain was minimal (but not zero) for targets around the axis of rotation (situation 2). Situation 3 has not been investigated in detail so far.