Temperature compensation in the vestibulo-ocular reflex: a novel hypothesis of cerebellar function

Some ectothermic animals are subject to changes of body temperature during routine activity. How are they able to maintain co-ordinated behaviour? Analysis of the available evidence on the effects of temperature on the vestibulo-ocular reflex suggests that there will be a degree of automatic temperature compensation. Temperature will increase the gain of some components of the reflex, and decrease the gain of others resulting in a reduced temperature sensitivity of the overall reflex. It is suggested that the cerebellum may provide the balance of temperature compensation required to maintain adequate reflex function. The hypothesis is that type III (bidirectionally sensitive) Purkinje cells receive temperature information as a common-mode signal from the opposing labyrinths, and use this information to regulate the gain of the vestibulo-ocular reflex pathway.     

Simulation of adaptive modification of the vestibulo-ocular reflex with an adaptive filter model of the cerebellum

An adaptive linear filter model of the cerebellum (Fujita, 1982), which functions as a phase lead or lag compensator with learning capability, is applied to a problem of the cerebellar control of the vestibuloocular reflex (VOR). Under the assumption that the cerebellar flocculus accounts for adaptive modification of dynamic characteristics of the VOR, the cerebellar model was incorporated into a linear control model of the oculomotor system. The results of a simulation study are in good agreement with experimental data on eye movement.     

Plasticity in the adult vestibulo-ocular reflex arc.

Human subjects with maintained reversal of their horizontal field of vision exhibit very substantial adaptive changes in their 'horizontal' vestibulo-ocular reflex (v.o.r.). Short durations (8 min) of vision reversal during natural head movement led to 20% v.o.r. attenuation while long periods (4 weeks) eventually led to approximate reversal of the reflex. The reversed condition is approached by a complex, but highly systematic, series of changes in gain and phase of the reflex response relative to normal. Recovery after return to normal vision exhibits a similar duration, but different pattern, to that of the original adaptation. A chronic cat preparation with long-term optical reversal of vision has now been developed and shows similar adaptive and recovery changes at low test stimulus amplitudes, but different patterns of adaptive response at high amplitudes. An adaptive neural model employing known vestibulo-ocular pathways is proposed to account for these experimentally observed plastic changes. The model is used to predict the adapted response to patterns of stimulation extending beyond the range of experimental investigation.     

An adaptive gaze stabilization controller inspired by the vestibulo-ocular reflex

The vestibulo-ocular reflex stabilizes vision in many vertebrates. It integrates inertial and visual information to drive the eyes in the opposite direction to head movement and thereby stabilizes the image on the retina. Its adaptive nature guarantees stable vision even when the biological system undergoes dynamic changes (due to disease, growth or fatigue etc), a characteristic especially desirable in autonomous robotic systems. Based on novel, biologically plausible neurological models, we have developed a robotic testbed to qualitatively evaluate the performance of these algorithms. We show how the adaptive controller can adapt to a time varying plant and elaborate how this biologically inspired control architecture can be employed in general engineering applications where sensory feedback is very noisy and/or delayed.     

Simulation of adaptive mechanisms in the vestibulo-ocular reflex

The vestibulo-ocular reflex (VOR), which stabilizes the eyes in space during head movements, can undergo adaptive modification to maintain retinal stability in response to natural or experimental challenges. A number of models and neural sites have been proposed to account for this adaptation but these do not fully explain how the nervous system can detect and correct errors in both gain and phase of the VOR. This paper presents a general error correction algorithm based on the multiplicative combination of three signals (retinal slip velocity, head position, head velocity) directly relevant to processing of the VOR. The algorithm is highly specific, requiring the combination of particular sets of signals to achieve compensation. It is robust, with essentially perfect compensation observed for all gain (0.25X–4.0X) and phase (-180°–+180°) errors tested. Output of the model closely resembles behavioral data from both gain and phase adaptation experiments in a variety of species. Imposing physiological constraints (no negative activation levels or changes in the sign of unit weights) does not alter the effectiveness of the algorithm. These results suggest that the mechanisms implemented in our model correspond to those implemented in the brain of the behaving organism. Predictions concerning the nature of the adaptive process are specific enough to permit experimental verification using electrophysiological techniques. In addition, the model provides a strategy for adaptive control of any first order mechanical system.     

Eye stabilization by statocyst mediated oculomotor reflex inNautilus

Summary Nautilus pompilius can rotate its eye relative to its body so as to compensate for changes in its body orientation and maintain its eye fixed with respect to gravity. An ocular compensation reflex stabilizes its eye about the pitch axis against the rocking motions that occur as the animal swims by jet propulsion. The eye is not held absolutely still, as 1–2° spontaneous rotations occur even if the animal is clamped.If the animal is held in an unnatural orientation (rotated about the axis through its laterally directed eyes) the counterrotation of the eye is maintained for many minutes; it may compensate for 50–90% of imposed tilts up to ±30°. If the nautilus is tilted suddenly forward or backward, its compensation reflex is 50% complete within 0.3 s, and is complete in 1–2 s. The time course of the responses explains how the eye, during the 1 Hz rocking caused by swimming, can be held fixed in space to within 1–4°. The ocular compensation of each eye is mediated largely by the homolateral statocyst, as is shown by unilateral and bilateral ablation. The effect of ocular compensation is to keep image orientation on the retina fixed relative to gravity, and to prevent large rotational image motions from being caused by the nautilus's own swimming.This work would not have been possible without the fishing skill and the hospitality of the people of Bindoy, Negros Oriental, The Republic of the Philippines. We especially thank Mr. Wilson Vailoces who arranged for capture of experimental animals. We are indebted to Mr. Walter Schneider for his technical assistance on shipboard. This study, a part of the RV Alpha Helix Southeast Asian Expedition was supported by the National Science Foundation under grants of 74-01883 and OCE 74-02888 to the Scripps Institution of Oceanography and BM 575-01149 to Iowa State University. NIH Grant R01-EY01539 to P. Hartline supported data analyses.     

"Velocity leakage" in the pigeon vestibulo-ocular reflex

The transfer characteristics of the vestibuloocular reflex (VOR), and of the semicircular canal primary afferents (SCPAs) that drive it, have been studied in several species. In monkeys and cats, the dominant time constant describing horizontal VOR dynamics ( _hu ) is longer than that ( _c ) of horizontal SCPAs. This lengthening of the time constant has been attributed to a velocity storage mechanism that has been modeled as a positive feedback loop in the VOR pathways. We have studied the transfer characteristics of horizontal and vertical VOR and SCPAs in unanesthetized pigeons. In this species the dominant time constants of both the horizontal and vertical VOR ( _hv and _vv ) are shorter than _c . This finding indicates that time constants characterizing the lower frequency response of the VOR can be lengthened or shortened depending on the species. We propose that in the pigeon the velocity leakage mechanism can be modeled by substituting negative feedback for positive feedback in the model of the VOR pathways. Negative feedback can also account for the further shortening of _hu and _vv as VOR gain increases with arousal. Additionally, making the negative feedback loop nonlinear can model the dependency of lower frequency VOR phase on amplitude, and skew in VOR waveforms. Pigeon VOR and SCPA dynamics also differ in their adaptive properties and higher frequency behavior. A predominance of input from highly adaptive SCPAs is proposed to account for the increased adaptation of the vertical VOR as compared with SCPAs overall. A pure time-delay associated with VOR operation can explain the phase lag of the VOR relative to SCPAs at higher frequencies.     

Neural network models of velocity storage in the horizontal vestibulo-ocular reflex

The vestibulo-ocular reflex (VOR) produces compensatory eye movements by utilizing head rotational velocity signals from the semicircular canals to control contractions of the extraocular muscles. In mammals, the time course of horizontal VOR is longer than that of the canal signals driving it, revealing the presence of a central integrator known as velocity storage. Although the neurons mediating VOR have been described neurophysiologically, their properties, and the mechanism of velocity storage itself, remain unexplained. Recent models of integration in VOR are based on systems of linear elements, interconnected in arbitrary ways. The present study extends this work by modeling horizontal VOR as a learning network composed of nonlinear model neurons. Network architectures are based on the VOR arc (canal afferents, vestibular nucleus (VN) neurons and extraocular motoneurons) and have both forward and lateral connections. The networks learn to produce velocity storage integration by forming lateral (commissural) inhibitory feedback loops between VN neurons. These loops overlap and interact in a complex way, forming both fast and slow VN pathways. The networks exhibit some of the nonlinear properties of the actual VOR, such as dependency of decay rate and phase lag upon input magnitude, and skewing of the response to higher magnitude sinusoidal inputs. Model VN neurons resemble their real counterparts. Both have increased time constant and gain, and decreased spontaneous rate as compared to canal afferents. Also, both model and real VN neurons exhibit rectification and skew. The results suggest that lateral inhibitory interactions produce velocity storage and also determine the properties of neurons mediating VOR. The neural network models demonstrate how commissural inhibition may be organized along the VOR pathway.     

The vestibulo-ocular reflex and velocity storage in spinocerebellar ataxia 8

The autosomal dominant spinocerebellar ataxias (SCAs) are a group of neurodegenerative diseases characterized by progressive instability of posture and gait, incoordination, ocular motor dysfunction, and dysarthria due to degeneration of cerebellar and brainstem neurons. Among the more than 20 genetically distinct subtypes, SCA8 is one of several wherein clinical observations indicate that cerebellar dysfunction is primary, and there is little evidence for other CNS involvement. The aim of the present work was to study the decay of the horizontal vestibulo-ocular reflex (VOR) after a short period of constant acceleration to understand the pathophysiology of the VOR due to cerebellar Purkinje cell degeneration in SCA8. The VOR was recorded in patients with genetically defined SCA8 during rotation in the dark. Moderate to severely affected patients had a qualitatively intact VOR, but there were quantitative differences in the gain and dynamics compared to normal controls. During angular velocity ramp rotations, there was a reversal in the direction of the VOR that was more pronounced in SCA8 compared to controls. Modeling studies indicate that there are significant changes in the velocity storage network, including abnormal feedback of an eye position signal into the network that contributes to this reversal. These and other results will help to identify features that are diagnostic for SCA subtypes and provide new information about selective vulnerability of neurons controlling vestibular reflexes.     

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     

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.     

Is the adaptation model a valid description of the vestibulo-ocular reflex?

The pendulum model of the vestibulo-ocular reflex, including the effects of adaptation, has been evaluated using the responses of 36 normal subjects to impulsive stimuli of 128 and 256°/s. Estimates of the model parameters such as the time constants, the slow velocity threshold, and the minimum stimulus required to produce an after-nystagmus have been obtained using a new analytical technique. Although some of the data support the validity of the adaptation model, evidence is presented to demonstrate that the overall applicability of the model is limited.     

Interaction of the angular and linear components of the horizontal vestibulo-ocular reflex in the pigeon

Pigeons were exposed to centric and eccentric horizontal rotations in darkness by velocity trapezoid. Different in sign the duration alterations of the opposite directed horizontal eye nystagmus occurred during otolith membrane shifts in sagittal as well as frontal planes. A direct dependence was found between the duration alterations of the primary nystagmus phase and the peak value alterations of its slow phase velocity under increased (but not decreased) centrifugal force. In the both cases, if duration of the primary nystagmus phase was enlarged, duration of its secondary phase was diminished and vice versa. It suggests the otolith component does not decay up to zero by constant velocity and at once after rotation; by deceleration it is biphasic. In affirms the own hypothesis that the linear component is asymmetric central neuronal activity that modifies the canal component even if this activity by itself is not enough for eye movement initiation.     

The development of the static vestibulo-ocular reflex in the Southern Clawed Toad,Xenopus laevis

In the clawed toad, Xenopus laevis, the static vestibulo-ocular reflex appears in 3 days old tadpoles (developmental stage 42) (Fig. 2). The amplitude and gain of this reflex increase up to stage 52, and then decrease to an almost constant value at stage 60 and older tadpoles (Fig. 3). The most effective roll angle gradually increases during development (Fig. 4). The size of the sensory epithelia reaches the final value at the end of the premetamorphic period (stage 56) (Fig. 5). The small-cellular medial ventral vestibular nucleus (VVN) reaches its maximal number of neurons before the large-cellular lateral VVN. Cell death is more pronounced in the medial than in the lateral part of the VVN. In the dorsal vestibular nucleus (DVN), the numerical development of the small and large neurons is similar to that in the small-cellular medial and large-cellular lateral portion of the VVN (Fig. 7). The results demonstrate that labyrinth and oculomotor centres are anatomically connected before the labyrinth and the vestibular nuclei are fully developed. We discuss the possibility that the ciliary polarity pattern of the sensory epithelium is radial during the first period of life, and changes to the vertebrate fan-type pattern during the second week of life. According to the increase of gain during the first three weeks of life, an increase of the spontaneous activity of vestibular neurons may occur during this period.     

The development of the static vestibulo-ocular reflex in the Southern Clawed Toad,Xenopus laevis

The static vestibulo-ocular reflex was investigated in tadpoles at different times following unilateral destruction of the labyrinth during the period of early organogenesis and premetamorphosis. Balance compensation is completed after a few weeks, while gain compensation only occurs partially (Figs. 2-4). Tadpoles hemilabyrinthectomized in the age of 2.5 days (stage 38) develop no vestibular nuclei on their lesioned side, while tadpoles operated later in their life, possess these nuclei (Figs. 5, 6) even if they were not detectable at the operation day (Fig. 7). For their dorsal vestibular nucleus (DVN), the number of neurons is usually larger on the intact than on the lesioned side; while for the ventral vestibular nucleus (VVN), there is either numerical symmetry or a transient decrease of cell number on the intact side (Fig. 5). The results demonstrate that vestibular compensation occurs even if vestibular nuclei have developed only on one side, i.e. the vestibular commissure is not a prerequisite for a successful compensation process. It is discussed whether the use of extra-vestibular error signals for balance but not for gain compensation may cause the differences in time courses of both compensation processes.     

The development of the static vestibulo-ocular reflex in the Southern Clawed Toad,Xenopus laevis

Summary Acute hemilabyrinthectomized tadpoles of the Southern Clawed Toad (Xenopus laevis), younger than stage 47 (about 6 days old), perform no static vestibulo-ocular reflex (Fig. 1). Older acute lesioned animals respond with compensatory movements of both eyes during static roll. Their threshold roll angle, however, depends on the developmental stage. For lesioned stages 60 to 64, it is 75° while stage 52 to 56 tadpoles respond even during a lateral roll of 15° (Figs. 1 and 2). Selective destruction of single macula and crista organs revealed that the static vestibulo-ocular reflex is evoked by excitation of the macula utriculi (Figs. 3 and 4) even in young tadpoles.The results demonstrate that bilateral projections of the vestibular apparatus must have developed at the time of occurrence of the static VOR, that during the first week of life the excitation of a single labyrinth is subthreshold (Fig. 1). We discuss the possibility whether the loss of the static VOR during the prometamorphic period of life (Fig. 2) is caused by increasing formation of multimodal connections in the vestibular pathway.Abbreviations eye angle - roll angle - () response characteristic - A response amplitude - G response gain - VOR vestibulo-ocular reflex