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     

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.     

Tests of a linear model of visual-vestibular interaction using the technique of parameter estimation

The goal of this study was to test whether a superposition model of smooth-pursuit and vestibulo-ocular reflex (VOR) eye movements could account for the stability of gaze that subjects show as they view a stationary target, during head rotations at frequencies that correspond to natural movements. Horizontal smooth-pursuit and the VOR were tested using sinusoidal stimuli with frequencies in the range 1.0–3.5 Hz. During head rotation, subjects viewed a stationary target either directly or through an optical device that required eye movements to be approximately twice the amplitude of head movements in order to maintain foveal vision of the target. The gain of compensatory eye movements during viewing through the optical device was generally greater than during direct viewing or during attempted fixation of the remembered target location in darkness. This suggests that visual factors influence the response, even at high frequencies of head rotation. During viewing through the optical device, the gain of compensatory eye movements declined as a function of the frequency of head rotation (P < 0.001) but, at any particular frequency, there was no correlation with peak head velocity (P > 0.23), peak head acceleration (P > 0.22) or retinal slip speed (P > 0.22). The optimal values of parameters of smooth-pursuit and VOR components of a simple superposition model were estimated in the frequency domain, using the measured responses during head rotation, as each subject viewed the stationary target through the optical device. We then compared the model's prediction of smooth-pursuit gain and phase, at each frequency, with values obtained experimentally. Each subject's pursuit showed lower gain and greater phase lag than the model predicted. Smooth-pursuit performance did not improve significantly if the moving target was a 10 deg × 10 deg Amsler grid, or if sinusoidal oscillation of the target was superimposed on ramp motion. Further, subjects were still able to modulate the gain of compensatory eye movements during pseudo-random head perturbations, making improved predictor performance during visual-vestibular interactions unlikely. We conclude that the increase in gain of eye movements that compensate for head rotations when subjects view, rather than imagine, a stationary target cannot be adequately explained by superposition of VOR and smooth-pursuit signals. Instead, vision may affect VOR performance by determining the context of the behavior. Received: 16 June 1997 / Accepted: 5 December 1997     

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.     

Three-dimensional vestibular eye and head reflexes of the chameleon: characteristics of gain and phase and effects of eye position on orientation of ocular rotation axes during stimulation in yaw direction

We investigated gaze-stabilizing reflexes in the chameleon using the three-dimensional search-coil technique. Animals were rotated sinusoidally around an earth-vertical axis under head-fixed and head-free conditions, in the dark and in the light. Gain, phase and the influence of eye position on vestibulo-ocular reflex rotation axes were studied. During head-restrained stimulation in the dark, vestibulo-ocular reflex gaze gains were low (0.1-0.3) and phase lead decreased with increasing frequencies (from 100 degrees at 0.04 Hz to < 30 degrees at 1 Hz). Gaze gains were larger during stimulation in the light (0.1-0.8) with a smaller phase lead (< 30 degrees) and were close to unity during the head-free conditions (around 0.6 in the dark, around 0.8 in the light) with small phase leads. These results confirm earlier findings that chameleons have a low vestibulo-ocular reflex gain during head-fixed conditions and stimulation in the dark and higher gains during head-free stimulation in the light. Vestibulo-ocular reflex eye rotation axes were roughly aligned with the head's rotation axis and did not systematically tilt when the animals were looking eccentrically, up- or downward (as predicted by Listing's Law). Therefore, vestibulo-ocular reflex responses in the chameleon follow a strategy, which optimally stabilizes the entire retinal images, a result previously found in non-human primates.     

Analysis and Modeling of Frequency-Specific Habituation of the Goldfish Vestibulo-Ocular Reflex

Modification of the vestibulo-ocular reflex (VOR) by vestibular habituation is an important paradigm in the study of neural plasticity. The VOR is responsible for rotating the eyes to maintain the direction of gaze during head rotation. The response of the VOR to sinusoidal rotation is quantified by its gain (eye rotational velocity/head rotational velocity) and phase difference (eye velocity phase—inverted head velocity phase). The frequency response of the VOR in naïve animals has been previously modeled as a high-pass filter (HPF). A HPF passes signals above its corner frequency with gain 1 and phase 0 but decreases gain and increases phase lead (positive phase difference) as signal frequency decreases below its corner frequency. Modification of the VOR by habituation occurs after prolonged low-frequency rotation in the dark. Habituation causes a reduction in low-frequency VOR gain and has been simulated by increasing the corner frequency of the HPF model. This decreases gain not only at the habituating frequency but further decreases gain at all frequencies below the new corner frequency. It also causes phase lead to increase at all frequencies below the new corner frequency (up to some asymptotic value). We show that habituation of the goldfish VOR is not a broad frequency phenomena but is frequency specific. A decrease in VOR gain is produced primarily at the habituating frequency, and there is an increase in phase lead at nearby higher frequencies and a decrease in phase lead at nearby lower frequencies (phase crossover). Both the phase crossover and the frequency specific gain decrease make it impossible to simulate habituation of the VOR simply by increasing the corner frequency of the HPF model. The simplest way to simulate our data is to subtract the output of a band-pass filter (BPF) from the output of the HPF model of the naïve VOR. A BPF passes signals over a limited frequency range only. A BPF decreases gain and imparts a phase lag and lead, respectively, as frequency increases and decreases outside this range. Our model produces both the specific decrease in gain at the habituating frequency, and the phase crossover centered on the frequency of habituation. Our results suggest that VOR habituation may be similar to VOR adaptation (in which VOR modification is produced by visual-vestibular mismatch) in that both are frequency-specific phenomena.     

Comparing the somal size and nuclear positions of the monkey stellate and coeliac ganglion cells

The stellate and coeliac ganglia of 2 Macaque monkeys were cut serially at 1 micron thickness and analysed. Results from the analysis of 82 stellate and 60 coeliac ganglion cells in 1 monkey show that in cross-sections, the neuronal nuclei may be eccentric, centric or nearly centric and remain so throughout the longitudinal extent of the neuron. In both ganglia, the majority of neurons possess eccentric nuclei, but in the coeliac ganglion, the percentage of neurons with centric and/or nearly centric nuclei is higher (41.7%) than that in the stellate ganglion (26.3%). While 5% of neurons in the coeliac ganglion are binucleated, no binucleated neurons were found in the stellate ganglion. The somal size ranges of the stellate (10-39 microns) and the coeliac (14.5-45 microns) ganglion neurons as obtained from both monkeys are quite close. The percentage frequency distribution of the stellate ganglion neurons in monkey 1 was also quite similar to that of the coeliac ganglion neurons. It is concluded that different neuronal size is not likely to be associated with different target organs.     

Effects of an increased air gap on the in vitro interaction of wireless phones with cardiac pacemakers

Several clinical and laboratory studies have demonstrated electromagnetic interaction between implantable cardiac pacemakers and hand-held wireless phones operated in close proximity. Current FDA and HIMA labeling guidelines indicate that a minimum separation of 6 in (15 cm) should be maintained between a hand-held wireless phone and an implanted pacemaker. This separation requirement does not distinguish between lateral locations on the chest and a perpendicular air gap. Evidence is provided here for a substantially reduced separation threshold when measured across an air gap rather than near the saline conductive media of a simulated torso. Twenty pacemaker-phone combinations involving 6 pacemakers and 9 phones were evaluated in vitro under worst-case conditions with respect to phone output power and pacemaker sensitivity. The phones represented CDMA, TDMA-11 Hz, TDMA-22 Hz, TDMA-50 Hz, and TDMA-217 Hz digital wireless technologies. Small increases in the perpendicular air gap between the phone and the saline surface resulted in a dramatic reduction in interaction. Approximately half of the 208 test runs exhibiting interaction at an air gap of 1 cm no longer resulted in interaction when the gap was increased to 2 cm. At a gap of 7.4 cm, the percentage of runs with interaction decreased to 1.4%. The overall interaction rate, considering a total of 8296 test runs from an earlier study, was less than 0.07% at a total perpendicular distance of 8.6 cm from the saline surface to the phone antenna axis. The perpendicular distance threshold of 8.6 cm was significantly less than the horizontal plane projection threshold of 19 cm previously reported. This difference is a function of the electromagnetic field coupling to the saline bath rather than field strength changes along the axis of the phone antenna. The results have implications for those making recommendations to pacemaker patients who may be unaware of this distinction.     

Analysis and Neural Network Modeling of the Nonlinear Correlates of Habituation in the Vestibulo-ocular Reflex

Through the process of habituation, continued exposure to low-frequency (0.01 Hz) rotation in the dark produced suppression of the low-frequency response of the vestibulo-ocular reflex (VOR) in goldfish. The response did not decay gradually, as might be expected from an error-driven learning process, but displayed several nonlinear and nonstationary features. They included asymmetrical response suppression, magnitude-dependent suppression for lower- but not higher-magnitude head rotations, and abrupt-onset suppressions suggestive of a switching mechanism. Microinjection of lidocaine into the vestibulocerebellum of habituated goldfish resulted in a temporary dishabituation. This suggests that the vestibulocerebellum mediates habituation, presumably through Purkinje cell inhibition of vestibular nuclei neurons. The habituated VOR data were simulated with a feed-forward, nonlinear neural network model of the VOR in which only Purkinje cell inhibition of vestibular nuclei neurons was varied. The model suggests that Purkinje cell inhibition may switch in to introduce nonstationarities, and cause asymmetry and magnitude-dependency in the VOR to emerge from the essential nonlinearity of vestibular nuclei neurons.     

Implications of gain modulation in brainstem circuits: VOR control system

Gain modulation is believed to be a common integration mechanism employed by neurons to combine information from various sources. Although gain fields have been shown to exist in some cortical and subcortical areas of the brain, their existence has not been explored in the brainstem. In the present modeling study, we develop a physiologically relevant simplified model for the angular vestibulo-ocular reflex (VOR) to show that gain modulation could also be the underlying mechanism that modifies VOR function with sensorimotor context (i.e. concurrent eye positions and stimulus intensity). The resulting nonlinear model is further extended to generate both slow and quick phases of the VOR. Through simulation of the hybrid nonlinear model we show that disconjugate eye movements during the VOR are an inevitable consequence of the existence of such gain fields in the bilateral VOR pathway. Finally, we will explore the properties of the predicted disconjugate component. We will demonstrate that the apparent phase characteristics of the disconjugate response vary with the concurrent conjugate component.     

Visual signals in an optomotor reflex: systems and information theoretic analysis

Compensatory optomotor reflexes were examined in crayfish (Procambarus clarkii) with oscillating sine wave gratings and step displacements of a single stripe. A capacitance transducer was used to measure the rotation of the eyestalk about its longitudinal axis. System studies reveal a spatial frequency response independent of velocity and stimulus amplitude and linear contrast sensitivity similar to that of neurons in the visual pathway. The reflex operates at low temporal frequencies (<0.002 Hz to 0.5 Hz) and exhibits a low-pass temporal frequency response with cut-off frequency of 0.1 Hz. Eyestalk rotation increases as a saturable function of the angular stimulus displacement. When compared to the oscillatory response, transient responses are faster, and they exhibit a lower gain for large stimulus displacements. These differences may reflect system nonlinearity and/or the presence of at least two classes of afferents in the visual pathway. Our metric for information transmission is the Kullback-Leibler (K-L) distance, which is inversely proportional to the probability of an error in distinguishing two stimuli. K-L distances are related to differences in responsiveness for variations in spatial frequency, contrast, and angular displacement. The results are interpreted in terms of the neural filters that shape the system response and the constraints that the K-L distances place on information transmission in the afferent visual pathway.     

The Effect of Visual Features on Jumping Spider Movements Across Gaps

Our objective was to determine whether an animal’s decisions to cross inhospitable open space are influenced by the visual characteristics of targets it can see across the space. We studied jumping spiders (Salticidae) in the genus Phidippus. We considered the effect of target size (short vs. tall) and distance (close vs. distant) in no-choice experiments. How often spiders approached close targets, regardless of target size, was not significantly different from how often they approached tall, distant targets, but they approached close targets of either size significantly more often than short, distant targets. When presented simultaneously with short, close and tall, distant targets the spiders’ choices did not differ significantly from random. We also tested for the effects of the contrast of targets with their background and found that the spiders crossed open space to reach green, but not white, targets, regardless of background. Finally, spiders were more likely to approach a green grass-like target rather than a target composed of geometric shapes. We conclude that target size, distance and appearance all influence the spiders’ willingness to cross open space.     

EEG-based communication and control: speed-accuracy relationships

People can learn to control mu (8–12 Hz) or beta (18–25 Hz) rhythm amplitude in the EEG recorded over sensorimotor cortex and use it to move a cursor to a target on a video screen. In our current EEG-based brain–computer interface (BCI) system, cursor movement is a linear function of mu or beta rhythm amplitude. In order to maximize the participant's control over the direction of cursor movement, the intercept in this equation is kept equal to the mean amplitude of recent performance. Selection of the optimal slope, or gain, which determines the magnitude of the individual cursor movements, is a more difficult problem. This study examined the relationship between gain and accuracy in a 1-dimensional EEG-based cursor movement task in which individuals select among 2 or more choices by holding the cursor at the desired choice for a fixed period of time (i.e., the dwell time). With 4 targets arranged in a vertical column on the screen, large gains favored the end targets whereas smaller gains favored the central targets. In addition, manipulating gain and dwell time within participants produces results that are in agreement with simulations based on a simple theoretical model of performance. Optimal performance occurs when correct selection of targets is uniform across position. Thus, it is desirable to remove any trend in the function relating accuracy to target position. We evaluated a controller that is designed to minimize the linear and quadratic trends in the accuracy with which participants hit the 4 targets. These results indicate that gain should be adjusted to the individual participants, and suggest that continual online gain adaptation could increase the speed and accuracy of EEG-based cursor control.     

Recovery of the vertical vestibulo-ocular reflex gain in rabbits submitted to bilateral and unilateral visual deprivation from birth

Rabbits were raised in complete darkness from birth to the age of 3 months. At this age, the animals were submitted to dynamic vestibular stimulation consisting of lateral sinusoidal oscillations of different frequencies and fixed amplitude. The vertical VOR, elicited in complete darkness, was then recorded. While the phase of the response was perfectly adequate to ensure head movements compensation, the gain values recorded were clearly reduced with respect to the values obtained in a normally raised control group of the same age. After exposure to light, the visually deprived animals showed a complete recovery of normal VOR gain values in a relatively short period of time. Another group of animals was submitted to monocular prolongation of light deprivation during the fourth month of life. After 2 weeks these rabbits displayed a clear unbalance of the VOR between the two eyes: the eye in which vision was allowed showed a complete recovery of VOR gain values, while the gain of the occluded eye remained unchanged. The present results confirm that visual experience in early life is necessary for a correct development of the VOR. If visual deprivation is limited to the first few months of life, the impairment of the reflex characteristics is completely reversible. Finally, data on monocular deprivation suggest that, in the rabbit, the neural structures which preside to the development of the vertical VOR compensatory properties are lateralized.     

Hearing and communication in blue monkeys (Cercopithecus mitis)

Hearing and vocal communication in blue monkeys (Cercopithecus mitis) was studied within an ecological context. Field measurements of the acoustical characteristics of the blue monkey's natural habitat were conducted in the Kibale forest (Uganda) and in Kakamega forest (Kenya). Measurements of background noise levels indicated that vocal communication pitched in the 100–1000-Hz frequency band would be relatively unimpeded by disruptive background noises. Furthermore, measurements of the propagation rate of audio signals indicated that calls pitched in the 125–200-Hz region penetrated the forest with minimal decrement in amplitude. Tests of the blue monkey's acoustic sensitivyty and range of hearing were conducted in the laboratory with standard audiometric procedures. Hearing in the blue monkey was characterized by a U-shaped function, with maximum sensitivity of about 5 dB SPL spanning a four-octave range from 1 to 16 kHz. The hearing of blue monkeys was superior to human hearing for tones below 500 Hz and above 8 kHz in frequency. A comparative analysis of primate hearing indicated that the blue monkey was approximately 18 dB more sensitive to low-frequency tones than the comparably sized, semi-terrestrial rhesus monkey (Macaca mulatta). Furthermore, blue monkeys exhibit phonatory specializations for vocal production in this relatively unused, low-frequency band of 125–200 Hz. These specializations for low-frequency vocal production and low-frequency hearing collectively act to increase the effective distance of long-range acoustic communication in the forest canopy.     

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.     

Opioid-Induced Nausea Involves a Vestibular Problem Preventable by Head-Rest

Background and Aims

Opioids are indispensable for pain treatment but may cause serious nausea and vomiting. The mechanism leading to these complications is not clear. We investigated whether an opioid effect on the vestibular system resulting in corrupt head motion sensation is causative and, consequently, whether head-rest prevents nausea.

Methods

Thirty-six healthy men (26.6±4.3 years) received an opioid remifentanil infusion (45 min, 0.15 μg/kg/min). Outcome measures were the vestibulo-ocular reflex (VOR) gain determined by video-head-impulse-testing, and nausea. The first experiment (n = 10) assessed outcome measures at rest and after a series of five 1-Hz forward and backward head-trunk movements during one-time remifentanil administration. The second experiment (n = 10) determined outcome measures on two days in a controlled crossover design: (1) without movement and (2) with a series of five 1-Hz forward and backward head-trunk bends 30 min after remifentanil start. Nausea was psychophysically quantified (scale from 0 to 10). The third controlled crossover experiment (n = 16) assessed nausea (1) without movement and (2) with head movement; isolated head movements consisting of the three axes of rotation (pitch, roll, yaw) were imposed 20 times at a frequency of 1 Hz in a random, unpredictable order of each of the three axes. All movements were applied manually, passively with amplitudes of about ± 45 degrees.

Results

The VOR gain decreased during remifentanil administration (p<0.001), averaging 0.92±0.05 (mean±standard deviation) before, 0.60±0.12 with, and 0.91±0.05 after infusion. The average half-life of VOR recovery was 5.3±2.4 min. 32/36 subjects had no nausea at rest (nausea scale 0.00/0.00 median/interquartile range). Head-trunk and isolated head movement triggered nausea in 64% (p<0.01) with no difference between head-trunk and isolated head movements (nausea scale 4.00/7.25 and 1.00/4.5, respectively).

Conclusions

Remifentanil reversibly decreases VOR gain at a half-life reflecting the drug’s pharmacokinetics. We suggest that the decrease in VOR gain leads to a perceptual mismatch of multisensory input with the applied head movement, which results in nausea, and that, consequently, vigorous head movements should be avoided to prevent opioid-induced nausea.     

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.     

Morphogenetic interactions between rotated skin cuffs and underlying stump tissues in regenerating axolotl forelimbs

Rotation of skin cuffs 180° around the longitudinal axis of the underlying tissues in the axolotl forelimb results in a high percentage of multiple regenerates after amputation through the rotated skin. Similar results occur after rotation of only the anteroposterior (A-P) axis of the skin. Rotation of only the proximodistal (Pr-Ds) axis of the skin results in normal regenerates whereas dorsoventral (D-V) axial skin rotation results in single regenerates with some disturbances in symmetry. Rotation of anterior or posterior half cuffs of skin produces results similar to those obtained after A-P rotation of full skin cuffs, and rotation of dorsal or ventral skin halves duplicates the results obtained by rotating full skin cuffs about the D-V axis. Skin cuffs rotated for periods from 6 months to over 2 years before amputation are also capable of causing multiple regenerates to form. No significant difference in the percentage of multiple regenerates was seen after skin rotation and limb amputation through shoulder, upper arm, and forearm levels. X-Radiation (4000 r) of either the skin or underlying tissues before skin rotation resulted in single regenerates after amputation. If a strip of normal skin was turned perpendicularly to the long axis of the irradiated underlying stump tissues, the regenerative response was blocked. In some of the above experiments, regenerates with longitudinally duplicated upper arm and forearm segments appeared. It is postulated that normally both the skin and the underlying limb tissues can influence morphogenesis during regeneration and that they work in harmony. In contrast, rotated skin and the underlying tissues each exert a morphogenetic influence upon the regenerating limb, and the regenerate is not able to integrate these disharmonious influences. This is reflected in the highly abnormal morphology of the regenerates. The nature of the morphogenetic influence disrupted by skin rotation is not yet known.