Reduction of the vertical vestibular-ocular reflex in military aircraft pilots exposed to tactical, high-performance flight.

Background: Exposure to high-performance flight stresses the vestibular system and may lead to adaptive changes in the vestibular responses of pilots. We investigated the vestibular-ocular reflex of pilots with different histories of flight exposure both with respect to hours of flight and flight conditions (tactical, high-performance vs. non-high-performance) to evaluate if and how adaptative changes are observable. Methods: We evaluated the vestibular-ocular reflex of aircraft pilots using the video Head Impulse Test. In study 1, we assessed three groups of military pilots: Group 1 had 68 pilots with few hours of flight experience (<300 h) in non-high-performance flight conditions; Group 2 had 15 pilots with many hours of flight (>3,000 h) and regularly flying tactical, high-performance flight conditions; Group 3 had eight pilots with many hours of flight (>3,000 h) but not exposed to tactical, high-performance flight conditions. In study 2, four trainee pilots were followed up and tested three times over a 4-year period: (1) <300 h of flight on civil aircraft; (2) shortly after exposure to aerobatic training and with <2,000 h of overall flight; and (3) after training on tactical, high-performance aircraft (F/A 18) and for more than 2,000 h of flight. Results: Study 1: Pilots of tactical, high-performance aircrafts (Group 2) had significantly lower gain values (p < 0.05) as compared to Groups 1 and 3, selectively for the vertical semicircular canals. They also had a statistically (p = 0.022) higher proportion (0.53) of pathological values in at least one vertical semicircular canal as compared to the other groups. Study 2: A statistically significant (p < 0.05) decrease in the rVOR gains of all vertical semicircular canals, but not of the horizontal canals, was observed. Two pilots had a pathological value in at least one vertical semicircular canal in the third test. Discussion: The results evidence a decrease in the gain of the vestibular-ocular reflex as measured with the video head impulse test for the vertical canals. This decrease appears to be associated with the exposure to tactical, high-performance flight rather than with the overall flight experience.

Effect of the Stimulus Duration on the Adaptation of the Optokinetic Afternystagmus.

Observing a rotating visual pattern covering a large portion of the visual field induces optokinetic nystagmus (OKN). If the lights are suddenly switched off, optokinetic afternystagmus (OKAN) occurs. OKAN is hypothesized to originate in the velocity storage mechanism (VSM), a central processing network involved in multi-sensory integration. During a sustained visual rotation, the VSM builds up a velocity signal. After the lights are turned off, the VSM discharges slowly, with OKAN as the neurophysiological correlate. It has been reported that the initial afternystagmus in the direction of the preceding stimulus (OKAN-I) can be followed by a reversed one (OKAN-II), which increases with stimulus duration up to 15 min. In 11 healthy adults, we investigated OKAN following optokinetic stimulus lasting 30 s, 3-, 5-, and 10-min. Analysis of slow-phase cumulative eye position and velocity found OKAN-II in only 5/11 participants. Those participants presented it in over 70% of their trials with longer durations, but only in 10% of their 30 s trials. While this confirms that OKAN-II manifests predominantly after sustained stimuli, it suggests that its occurrence is subject-specific. We also did not observe further increases with stimulus duration. Conversely, OKAN-II onset occurred later as stimulus duration increased (p = 0.02), while OKAN-II occurrence and peak velocity did not differ between the three longest stimuli. Previous studies on OKAN-I, used negative saturation models to account for OKAN-II. As these approaches have no foundation in the OKAN-II literature, we evaluated if a simplified version of a rigorous model of OKAN adaptation could be used in humans. Slow-phase velocity following the trials with 3-, 5-, and 10-min stimuli was fitted with a sum of two decreasing exponential functions with opposite signs (one for OKAN-I and one for OKAN-II). The model assumes separate mechanisms for OKAN-I, representing VSM discharge, and OKAN-II, described as a slower adaptation phenomenon. Although the fit was qualitatively imperfect, this is not surprising given the limited reliability of OKAN in humans. The estimated adaptation time constant seems comparable to the one describing the reversal of the vestibulo-ocular reflex during sustained rotation, suggesting a possible shared adaptive mechanism.

Cerebellar Rebound Nystagmus Explained as Gaze-Evoked Nystagmus Relative to an Eccentric Set Point: Implications for the Clinical Examination.

A brain stem/cerebellar neural integrator enables stable eccentric gaze. Cerebellar loss-of-function can cause an inability to maintain gaze eccentrically (gaze-evoked nystagmus). Moreover, after returning gaze to straight ahead, the eyes may drift toward the prior eye position (rebound nystagmus). Typically, gaze-evoked nystagmus decays during continuously held eccentric gaze. We hypothesized this adaptive behavior to be prerequisite for rebound nystagmus and thus predicted a correlation between the velocity decay of gaze-evoked nystagmus and the initial velocity of rebound nystagmus. Using video-oculography, eye position was measured in 11 patients with cerebellar degeneration at nine horizontal gaze angles (15° nasal to 25° temporal) before (baseline), during, and after attempted eccentric gaze at ± 30° for 20 s. We determined the decrease of slow-phase velocity at eccentric gaze and the slow-phase velocity of the subsequent rebound nystagmus relative to the baseline. During sustained eccentric gaze, eye drift velocity of gaze-evoked nystagmus decreased by 2.40 ± 1.47°/s. Thereafter, a uniform change of initial eye drift velocity relative to the baseline (2.40 ± 1.35°/s) occurred at all gaze eccentricities. The velocity decrease during eccentric gaze and the subsequent uniform change of eye drift were highly correlated (R2 = 0.80, p < 0.001, slope = 1.09). Rebound nystagmus can be explained as gaze-evoked nystagmus relative to a set point (position with least eye drift) away from straight-ahead eye position. To improve detection at the bedside, we suggest testing rebound nystagmus not at straight-ahead eye position but at an eccentric position opposite of prior eccentric gaze (e.g., 10°), ideally using quantitative video-oculography to facilitate diagnosis of cerebellar loss-of-function.

Measuring optokinetic after-nystagmus: potential for detecting patients with signs of visual dependence following concussion.

Concussed patients with chronic symptoms commonly report dizziness during exposure to environments with complex visual stimuli (e.g. supermarket aisles, busy crossroads). Such visual induced dizziness is well-known in patients with vestibular deficits, in whom it indicates an overreliance on visual cues in sensory integration. Considering that optokinetic after-nystagmus (OKAN) reflects the response of the central network integrating visual and vestibular self-motion signals (velocity storage network), we investigated OKAN in 71 patients [17 (23.9%) females, 30.36 ± 9.05 years old] who suffered from persistent symptoms after a concussion and presented clinical signs suggesting visual dependence. Data were retrospectively compared with 21 healthy individuals [13 (61.9%) females, 26.29 ± 10.00 years old]. The median values of the slow cumulative eye position and of the time constant of OKAN were significantly higher in patients than in healthy individuals (slow cumulative eye position: 124.15 ± 55.61° in patients and 77.87 ± 45.63° in healthy individuals-p = 0.012; time constant: 25.17 ± 10.27 s in patients and 13.95 ± 4.92 s in healthy individuals-p = 0.003). The receiving operating curve (ROC) estimated on the time constant had an overall area under the curve of 0.73. Analysis of the ROC suggests that a test measuring the OKAN time constant could obtain a sensitivity of 0.73 and specificity of 0.72 in determining the origin of the visual-related disturbances in those patients (threshold 16.6 s). In a subset of 43 patients who also performed the Sensory Organization Test (SOT), the proposed OKAN test was twice as sensitive as the SOT. This study suggests that concussed patients with persisting visual symptoms may have an underlying impairment of the velocity storage mechanism and that measuring the OKAN time constant can objectify such impairment.

Prevalence and Characteristics of Physiological Gaze-Evoked and Rebound Nystagmus: Implications for Testing Their Pathological Counterparts.

Objective: Cerebellar diseases frequently affect the ocular motor neural velocity-to-position integrator by increasing its leakiness and thereby causing gaze-evoked nystagmus (GEN) and rebound nystagmus (RN). Minor leakiness is physiological and occasionally causes GEN in healthy humans. We aimed to evaluate the characteristics of GEN/RN in healthy subjects for better differentiation between physiological and pathological GEN/RN. Methods: Using video-oculography, eye position was measured in 14 healthy humans at straight ahead eye position before and after, and during 30 s of ocular fixation at 4 horizontal eccentric targets between 30° and 45°. We determined the eye drift velocity and the prevalence of nystagmus before/during/after eccentric fixation. Results: Eye drift velocities during (range: 0.62 ± 0.53°/s to 1.78 ± 0.69°/s) and after eccentric gaze (range: 0.28 ± 0.52°/s to 1.48 ± 1.02°/s) increased with the amount of gaze eccentricity (30°-45°). During continuous eccentric gaze, eye drift velocities decreased by 0.41 ± 0.18°/s at 30°, and 0.84 ± 0.38°/s at 45° gaze eccentricity. GEN was elicited in 71% of subjects at 30° gaze eccentricity. Twenty-one percent showed RN thereafter. This prevalence increased to 100% (GEN)/72% (RN) at 45° gaze eccentricity. RN found after 30° gaze eccentricity was of low velocity (0.82 ± 0.21°/s) and occurred after minor drift velocity decrease during prior eccentric gaze (0.43 ± 0.15°/s). Conclusion: GEN and RN should be tested using horizontal gaze eccentricities of <30°, since most healthy subjects physiologically show GEN and RN at higher eccentricities. In case of an uncertain result, both the reduction of eye drift velocity during eccentric gaze and the velocity of RN can be analyzed to distinguish physiological from pathological nystagmus.

Combined Optokinetic Treatment and Vestibular Rehabilitation to Reduce Visually Induced Dizziness in a Professional Ice Hockey Player After Concussion: A Clinical Case.

Background: The appropriate detection and therapy of concussion symptoms are of great importance to avoid long-term impairment and absence from pre-concussive activities, such as sport, school or work. Post-traumatic headache and dizziness are known as risk factors of persistent symptoms after a concussion. Dizziness has even been classified as a predictor for symptom persistence. One type of dizziness, which has never been considered is visually induced dizziness (VID) often develops as a consequence of vestibular impairment. This manuscript presents the clinical case of a 25-year-old male, professional ice hockey player, whereby a therapeutic approach to VID after concussion is demonstrated. Case: A detailed interdisciplinary clinical and laboratory-assisted neurological, neurovestibular and ocular-motor examination was performed 20 days post-concussion, which indicated VID symptoms. Thus, the player qualified for a 5-day combined vestibular, balance and optokinetic therapy, which aimed to reduce the player's increased sensitivity to visual information. Each treatment day consisted of two sessions: vestibular/ocular-motor training and exposure to optokinetic stimuli combined with postural control exercises. The optokinetic stimulus was delivered in the form of a rotating disk. VID symptoms were recorded daily via posturography and a visual analog scale prior to the optokinetic sessions. The player improved over the course of each treatment day and was able to return to ice hockey 15 days after the final treatment session. Three months later the player reported no symptoms in the follow up questionnaire. Conclusion: The combination of vestibular, balance and optokinetic therapy led to remission of VID symptoms in a professional ice hockey player after multiple concussions, within a short time frame after his last concussion. Thus, this case study highlights the significant benefit of treating post-concussive VID symptoms utilizing a multi-modal approach.

Non-linearity in gaze holding: Experimental results and possible mechanisms.

Cerebellar impairment may cause deficits in horizontal gaze holding, leading to centrifugal gaze-evoked nystagmus during fixation of eccentric targets. Healthy individuals show a weak drift leading to physiological nystagmus only at large gaze angles. These drifts are due to imperfect memory of the neural circuitry generating the eye position signals by integration of velocity signals. The cerebellum plays a crucial role in reducing the "leakiness" of this neural integrator. This neural integrator has been traditionally modeled as a first order low-pass filter, implying a linear relation between drift velocity and eye eccentricity. Evidences of a non-linear behavior, however, can be found in the literature. In a recent series of papers we showed that the eye drift velocity (V) can be descriptively modeled as a tangent function of gaze eccentricity (P) with the following equation: V=k2/k1tan(k1P). Notably, the two parameters have distinct roles: k1 regulates the rate of compression of the tangent, exclusively determining the non-linearity; k2 is a pure scaling factor. This descriptive model robustly fitted the data of healthy individuals both at baseline (n=50) and following transient cerebellar impairment induced by controlled amounts of alcohol [blood alcohol content 0.06% (n=15) and 0.1% (n=15)] and of patients with chronic cerebellar impairment of various origin (n=20). Interestingly, alcohol selectively changed the scaling factor k2, evidencing that an overall, transient cerebellar impairment does not impact the non-linear behavior. Patients with cerebellar degeneration, on the other hand, showed a change in both k1 and k2, implying a role of the cerebellum in limiting the range of eye positions where the non-linearity becomes relevant. Non-linearity has been reported in literature for both the neural integrator and the eye plant. While previous models using a neural network attempted to reproduce the non-linear behavior of the brainstem, we propose a block diagram reproducing the observed PV tangent relation by introducing a position dependency in the parameters of the cerebellar feedback loop.

Functional Head Impulse Test in Professional Athletes: Sport-Specific Normative Values and Implication for Sport-Related Concussion.

Dizziness, slow visual tracking, or blurred vision following active head (or body) movements are among the most common symptoms reported following sport-related concussion, often related to concurrent dysfunctions of the vestibular system. In some cases, symptoms persist even if bedside and auxiliary standard vestibular tests are unremarkable. New functional tests have been developed in recent years to objectify neurological alterations that are not captured by standard tests. The functional head impulse test (fHIT) requires the patient to recognize an optotype that is briefly flashed during head rotations with various angular accelerations (2,001-6,000 deg/s2) and assesses the proportion if correct answers (pca). 268 active professional athletes (23.70 ± 5.32y) from six different sports were tested using fHIT. Pca were analyzed both pooling head acceleration in the range of 2,001-6,000 deg/s2 and computing a single pca value for each 1,000 deg/s2 bin in the range 2,001-8,000 deg/s2. No significant difference (p = 0.159) was found between responses to head impulses in the plane of horizontal (pca: 0.977) and vertical semicircular canals (pca: 0.97). The sport practiced had a major effect on the outcome of the fHIT. Handball players achieved a better performance (p < 0.001) than the whole athlete group, irrespective of the direction of head impulses. The pca achieved by athletes practicing snowboard, bob and skeleton were instead significantly below those of the whole athlete group (p < 0.001) but only when vertical head impulses were tested. Overall, pca declined with increasing head acceleration. The decline was particularly evident in the range not included in the standard fHIT exam, i.e., 6,001-8,000 deg/s2 for horizontal and 5,001-8,000 deg/s2 for vertical head impulses. When vertical head impulses were tested, athletes practicing snowboard, bob and skeleton (non-ball sports) showed, beside the lower overall pca, also a steeper decline as a function of vertical head acceleration. The findings suggest that: (1) functional VOR testing can help understanding sport-specific VOR requirements; (2) the fHIT is able to detect and objectify subtle, sport-specific changes of functional VOR performance; (3) if sport-specific normative values are used, the fHIT test procedure needs to be optimized, starting from the highest acceleration to minimize the number of head impulses.

Artificial intelligence for understanding concussion: Retrospective cluster analysis on the balance and vestibular diagnostic data of concussion patients.

OBJECTIVES: We propose a bottom-up, machine-learning approach, for the objective vestibular and balance diagnostic data of concussion patients, to provide insight into the differences in patients' phenotypes, independent of existing diagnoses (unsupervised learning). METHODS: Diagnostic data from a battery of validated balance and vestibular assessments were extracted from the database of the Swiss Concussion Center. The desired number of clusters within the patient database was estimated using Calinski-Harabasz criteria. Complex (self-organizing map, SOM) and standard (k-means) clustering tools were used, and the formed clusters were compared. RESULTS: A total of 96 patients (81.3% male, age (median [IQR]): 25.0[10.8]) who were expected to suffer from sports-related concussion or post-concussive syndrome (52[140] days between diagnostic testing and the concussive episode) were included. The cluster evaluation indicated dividing the data into two groups. Only the SOM gave a stable clustering outcome, dividing the patients in group-1 (n = 38) and group-2 (n = 58). A large significant difference was found for the caloric summary score for the maximal speed of the slow phase, where group-1 scored 30.7% lower than group-2 (27.6[18.2] vs. 51.0[31.0]). Group-1 also scored significantly lower on the sensory organisation test composite score (69.0[22.3] vs. 79.0[10.5]) and higher on the visual acuity (-0.03[0.33] vs. -0.14[0.12]) and dynamic visual acuity (0.38[0.84] vs. 0.20[0.20]) tests. The importance of caloric, SOT and DVA, was supported by the PCA outcomes. Group-1 tended to report headaches, blurred vision and balance problems more frequently than group-2 (>10% difference). CONCLUSION: The SOM divided the data into one group with prominent vestibular disorders and another with no clear vestibular or balance problems, suggesting that artificial intelligence might help improve the diagnostic process.

More far is more right: Manual and ocular line bisections, but not the Judd illusion, depend on radial space.

Line bisection studies generally find a left-to-right shift in bisection bias with increasing distance between the observer and the target line, which may be explained by hemispheric differences in the processing of proximo-distal information. In the present study, the segregation between near and far space was further characterized across the motor system and contextual cues. To this aim, 20 right-handed participants were required to perform a manual bisection task of simple lines presented at three different distances (60, 90, 120 cm). Importantly, the horizontal spatial location of the line was manipulated along with the viewing distance to investigate more deeply the hemispheric engagement in the transition from near to far space. As the motoric component of the manual task producing activations of left premotor and motor areas may be partially responsible for the observed transition, participants were also involved in an ocular bisection task. Further, participants were required to bisect Judd variants of the target lines, which are known to elicit a Müller-Lyer-type illusion. Since the Judd illusion depends on areas in the ventral visual stream, we predicted that line bisections of Judd-type lines would be unaffected by viewing distance. Results showed that manual bisection of simple lines was modulated separately by viewing distance and the hemispace of presentation, with this pattern being similar for ocular bisection. Critically, bisections in the Judd illusion task were not modulated by viewing distance, whether performed by hand or by eye. Overall, these findings support the hypothesis that the right hemisphere plays a dominant role in the processing of space close to the body. They also present novel evidence for a general reduction of this dominance at farther distances, whether hand motor actions are involved or not. Finally, our study documents a dissociation between the processing of pure visuospatial information and that of a visual illusion as a function of viewing distance, supporting more generally the dorsal/near space and the ventral/far space segregation.

Determinants of Motion Sickness in Tilting Trains: Coriolis/Cross-Coupling Stimuli and Tilt Delay.

Faster trains require tilting of the cars to counterbalance the centrifugal forces during curves. Motion sensitive passengers, however, complain of discomfort and overt motion sickness. A recent study comparing different control systems in a tilting train, suggested that the delay of car tilts relative to the curve of the track contributes to motion sickness. Other aspects of the motion stimuli, like the lateral accelerations and the car jitters, differed between the tested conditions and prevented a final conclusion on the role of tilt delay. Nineteen subjects were tested on a motorized 3D turntable that simulated the roll tilts during yaw rotations experienced on a tilting train, isolating them from other motion components. Each session was composed of two consecutive series of 12 ideal curves that were defined on the bases of recordings during an actual train ride. The simulated car tilts started either at the beginning of the curve acceleration phase (no-delay condition) or with 3 s of delay (delay condition). Motion sickness was self-assessed by each subject at the end of each series using an analog motion sickness scale. All subjects were tested in both conditions. Significant increases of motion sickness occurred after the first sequence of 12 curves in the delay condition, but not in the no-delay condition. This increase correlated with the sensitivity of motion sickness, which was self-assessed by each subject before the experiment. The second sequence of curve did not lead to a significant further increase of motion sickness in any condition. Our results demonstrate that, even if the speed and amplitude are as low as those experienced on tilting trains, a series of roll tilts with a delay relative to the horizontal rotations, isolated from other motion stimuli occurring during a travel, generate Coriolis/cross-coupling stimulations sufficient to rapidly induce motion sickness in sensitive individuals. The strength and the rapid onset of the motion sickness reported confirm that, even if the angular velocity involved are low, the Coriolis/cross-coupling resulting from the delay is a major factor in causing sickness that can be resolved by improving the tilt timing relative to the horizontal rotation originating from the curve.

Cross-coupling vestibular stimulation: motion sickness and the vestibulo-sympathetic reflex.

Motion sickness is associated with a variety of autonomic symptoms, presumably due to proximity or functional interconnectivity between the autonomic centers in the brainstem and the vestibular system. A direct influence of the vestibular system on cardiovascular variables, defined as the vestibulo-sympathetic reflex, has been reported previously. Our aim was to investigate the sudomotor components of the autonomic responses associated with motion sickness during passive cross-coupling stimulation ("roll while rotating"). Healthy subjects (n = 17) were rotated at 40°/s around an earth-vertical yaw axis alone and in combination with sinusoidal roll oscillations (0.2 Hz). Motion sickness was assessed verbally every minute using a 1-10 scale, while recording DC and AC skin conductance levels (SCL) from the forehead. Yaw rotation alone provoked neither motion sickness nor variations of forehead sweating. Yet during cross-coupling stimulation all subjects reported motion sickness. Higher motion sickness scores (>5) were associated with significantly higher amplitudes of AC-SCL events compared to the lower scores (0.22 ± 0.01 vs. 0.11 ± 0.01 µS, respectively). Frequency domain analysis of the AC-SCL events revealed a peak at 0.2 Hz, coinciding with the frequency of the chair rolls. The total power of AC-SCL signals did not match the trend of motion sickness scores across conditions. We conclude that: (1) although SCL is related to motion sickness, it does not follow the perceived sickness closely; (2) the discrepancy between SCL and motion sickness and the rhythmic AC-SCL events could reflect a sudomotor component of the vestibulo-sympathetic reflex.

Gravity dependence of the effect of optokinetic stimulation on the subjective visual vertical.

Accurate and precise estimates of direction of gravity are essential for spatial orientation. According to Bayesian theory, multisensory vestibular, visual, and proprioceptive input is centrally integrated in a weighted fashion based on the reliability of the component sensory signals. For otolithic input, a decreasing signal-to-noise ratio was demonstrated with increasing roll angle. We hypothesized that the weights of vestibular (otolithic) and extravestibular (visual/proprioceptive) sensors are roll-angle dependent and predicted an increased weight of extravestibular cues with increasing roll angle, potentially following the Bayesian hypothesis. To probe this concept, the subjective visual vertical (SVV) was assessed in different roll positions (≤ ± 120°, steps = 30°, n = 10) with/without presenting an optokinetic stimulus (velocity = ± 60°/s). The optokinetic stimulus biased the SVV toward the direction of stimulus rotation for roll angles ≥ ± 30° (P < 0.005). Offsets grew from 3.9 ± 1.8° (upright) to 22.1 ± 11.8° (±120° roll tilt, P < 0.001). Trial-to-trial variability increased with roll angle, demonstrating a nonsignificant increase when providing optokinetic stimulation. Variability and optokinetic bias were correlated (R2 = 0.71, slope = 0.71, 95% confidence interval = 0.57-0.86). An optimal-observer model combining an optokinetic bias with vestibular input reproduced measured errors closely. These findings support the hypothesis of a weighted multisensory integration when estimating direction of gravity with optokinetic stimulation. Visual input was weighted more when vestibular input became less reliable, i.e., at larger roll-tilt angles. However, according to Bayesian theory, the variability of combined cues is always lower than the variability of each source cue. If the observed increase in variability, although nonsignificant, is true, either it must depend on an additional source of variability, added after SVV computation, or it would conflict with the Bayesian hypothesis.NEW & NOTEWORTHY Applying a rotating optokinetic stimulus while recording the subjective visual vertical in different whole body roll angles, we noted the optokinetic-induced bias to correlate with the roll angle. These findings allow the hypothesis that the established optimal weighting of single-sensory cues depending on their reliability to estimate direction of gravity could be extended to a bias caused by visual self-motion stimuli.

Gaze-evoked nystagmus induced by alcohol intoxication.

KEY POINTS: The cerebellum is the core structure controlling gaze stability. Chronic cerebellar diseases and acute alcohol intoxication affect cerebellar function, inducing, among others, gaze instability as gaze-evoked nystagmus. Gaze-evoked nystagmus is characterized by increased centripetal eye-drift. It is used as an important diagnostic sign for patients with cerebellar degeneration and to assess the 'driving while intoxicated' condition. We quantified the effect of alcohol on gaze-holding using an approach allowing, for the first time, the comparison of deficits induced by alcohol intoxication and cerebellar degeneration. Our results showed that alcohol intoxication induces a two-fold increase of centripetal eye-drift. We establish analysis techniques for using controlled alcohol intake as a model to support the study of cerebellar deficits. The observed similarity between the effect of alcohol and the clinical signs observed in cerebellar patients suggests a possible pathomechanism for gaze-holding deficits. ABSTRACT: Gaze-evoked nystagmus (GEN) is an ocular-motor finding commonly observed in cerebellar disease, characterized by increased centripetal eye-drift with centrifugal correcting saccades at eccentric gaze. With cerebellar degeneration being a rare and clinically heterogeneous disease, data from patients are limited. We hypothesized that a transient inhibition of cerebellar function by defined amounts of alcohol may provide a suitable model to study gaze-holding deficits in cerebellar disease. We recorded gaze-holding at varying horizontal eye positions in 15 healthy participants before and 30 min after alcohol intake required to reach 0.6‰ blood alcohol content (BAC). Changes in ocular-motor behaviour were quantified measuring eye-drift velocity as a continuous function of gaze eccentricity over a large range (±40 deg) of horizontal gaze angles and characterized using a two-parameter tangent model. The effect of alcohol on gaze stability was assessed analysing: (1) overall effects on the gaze-holding system, (2) specific effects on each eye and (3) differences between gaze angles in the temporal and nasal hemifields. For all subjects, alcohol consumption induced gaze instability, causing a two-fold increase [2.21 (0.55), median (median absolute deviation); P = 0.002] of eye-drift velocity at all eccentricities. Results were confirmed analysing each eye and hemifield independently. The alcohol-induced transient global deficit in gaze-holding matched the pattern previously described in patients with late-onset cerebellar degeneration. Controlled intake of alcohol seems a suitable disease model to study cerebellar GEN. With alcohol resulting in global cerebellar hypofunction, we hypothesize that patients matching the gaze-holding behaviour observed here suffered from diffuse deficits in the gaze-holding system as well.

Unravelling Stimulus Direction Dependency of Visual Acuity in Larval Zebrafish by Consistent Eye Displacements Upon Optokinetic Stimulation.

PURPOSE: Impairment of visual acuity (VA) can be seen early on in various diseases and has a major impact on patients' daily activities. Zebrafish is an important model for studying visual disorders. We developed a new method in zebrafish larva to easily and precisely measure the VA, which should allow for better estimation of affected vision such as after genetic manipulation or pharmacologic intervention. METHODS: We used an optokinetic reflex (OKR) paradigm with a staircase technique to estimate VA of zebrafish larva. Consistent eye displacements were used as the indicator for OKR. We measured VA and determined the dependence of VA on clockwise and counterclockwise horizontal stimulus directions. RESULTS: Visual acuity in zebrafish larva was estimated to be 0.179 ± 0.013 cyc/deg binocularly and 0.129 ± 0.008 cyc/deg (left eye) and 0.128 ± 0.012 cyc/deg (right eye) monocularly. We found within single subjects spatial frequency thresholds that showed highly significant differences between the two horizontal stimulus directions. Average higher and lower binocular thresholds were 0.181 ± 0.026 and 0.158 ± 0.014 cyc/deg, respectively. Importantly, no correlations were found between spatial frequency thresholds and average median peak slow-phase eye velocities (SPV) of OKR in all experiments. CONCLUSIONS: Consistent eye displacements evoked by OKR stimuli can be used as an indirect measure of VA in zebrafish larva. Conversely, using SPV of OKR to determine VA does not seem to be accurate. With our method, single larva showed significantly different VA depending on stimulus directions, which might reflect asymmetric maturation of retinal and/or visual pathway structures.

Dissociating vestibular and somatosensory contributions to spatial orientation.

Inferring object orientation in the surroundings heavily depends on our internal sense of direction of gravity. Previous research showed that this sense is based on the integration of multiple information sources, including visual, vestibular (otolithic), and somatosensory signals. The individual noise characteristics and contributions of these sensors can be studied using spatial orientation tasks, such as the subjective visual vertical (SVV) task. A recent study reported that patients with complete bilateral vestibular loss perform similar as healthy controls on these tasks, from which it was conjectured that the noise levels of both otoliths and body somatosensors are roll-tilt dependent. Here, we tested this hypothesis in 10 healthy human subjects by roll tilting the head relative to the body to dissociate tilt-angle dependencies of otolith and somatosensory noise. Using a psychometric approach, we measured the perceived orientation, and its variability, of a briefly flashed line relative to the gravitational vertical (SVV). Measurements were taken at multiple body-in-space orientations (-90 to 90°, steps of 30°) and head-on-body roll tilts (30° left ear down, aligned, 30° right ear down). Results showed that verticality perception is processed in a head-in-space reference frame, with a systematic SVV error that increased with larger head-in-space orientations. Variability patterns indicated a larger contribution of the otolith organs around upright and a more substantial contribution of the body somatosensors at larger body-in-space roll tilts. Simulations show that these findings are consistent with a statistical model that involves tilt-dependent noise levels of both otolith and somatosensory signals, confirming dynamic shifts in the weights of sensory inputs with tilt angle.

Moving in a Moving World: A Review on Vestibular Motion Sickness.

Motion sickness is a common disturbance occurring in healthy people as a physiological response to exposure to motion stimuli that are unexpected on the basis of previous experience. The motion can be either real, and therefore perceived by the vestibular system, or illusory, as in the case of visual illusion. A multitude of studies has been performed in the last decades, substantiating different nauseogenic stimuli, studying their specific characteristics, proposing unifying theories, and testing possible countermeasures. Several reviews focused on one of these aspects; however, the link between specific nauseogenic stimuli and the unifying theories and models is often not clearly detailed. Readers unfamiliar with the topic, but studying a condition that may involve motion sickness, can therefore have difficulties to understand why a specific stimulus will induce motion sickness. So far, this general audience struggles to take advantage of the solid basis provided by existing theories and models. This review focuses on vestibular-only motion sickness, listing the relevant motion stimuli, clarifying the sensory signals involved, and framing them in the context of the current theories.

Keeping an eye on serial order: Ocular movements bind space and time.

The present study examined whether traveling through serially-ordered verbal memories exploits overt visuospatial attentional resources. In a three-phase behavioral study, five single-digits were presented sequentially at one spatial location in phase 1, while recognition and verbal recall were tested in phases 2 and 3, respectively. Participants' spontaneous eye movements were registered along with the verbal responses. Results showed that the search and the retrieval of serially-ordered information were mediated by spontaneous ocular movements. Specifically, recognizing middle items of the memorized sequence required longer inspection times and, importantly, a greater involvement of overt attentional resources, than recognizing the serially first-presented item and, to a lesser extent, the last-presented item. Moreover, serial order was found to be spatially encoded from left-to-right, as eye position during vocal responses deviated the more to the right, the later the serial position of the retrieved item in the sequence. These findings suggest that overt spatial attention mediates the scanning of serial order representation.

Impaired tilt perception in Parkinson's disease: a central vestibular integration failure.

INTRODUCTION: Impaired balance control is a hallmark symptom in Parkinson's disease (PD). Altered sensory-motor integration contributes to the deficiency. We aimed to determine whether impaired vestibular signal processing added to the disorder. We exposed patients (N = 11; 68±6y) and age-matched healthy subjects (hS: N = 19; 65±11y) on a motion platform in complete darkness to two consecutive forward tilt movements (12 series; N = 24; overall 288 trials) and asked them to indicate which tilt was perceived larger. By combing tilt movements with translations we manipulated vestibular sensory input in order to investigate whether putative impairment resulted from a deficiency of the sensory organs (semicircular canals in 'single-SCC-cue-condition', otoliths in 'single-OT-cue-condition') themselves or to a sensory integration failure ('multi-cue-condition'). RESULTS: Tilt discrimination in the multi-cue-condition was inferior in patients compared to hS (p = 0.02). No significant differences between the two groups were found for both single-cue-conditions. Comparison of multi-cue-condition with a prediction resulting from the combination of both single-cue-conditions by optimal observer theory revealed that patients (p = 0.04), in contrast to hS, failed to efficiently combine SCC and OT information to improve tilt perception. CONCLUSION: We found that PD patients distinguished forward tilts less precise than hS, suggesting impaired vestibular perception. Tilt discrimination in patients, moreover, did not improve as much as in hS in conditions where both SCC and OT information was available compared to conditions where only SCC or OT cues were activated. The latter provides evidence that tilt misperception in PD most likely results from an integration failure of vestibular signals.