Otolith-ocular Reflex Research Articles

Papers presented at 2005 Annual Meeting of the German Audiology & Neurotology Group (ADANO)

The 2005 Annual Meeting of the German Audiology & Neurotology Group (ADANO), an integral part of the German Society of Otorhinolaryngology, Head & Neck Surgery was held in Berlin from September 29 – October 1, 2005. The meeting had a strong neurotological focus and the discussions were centered on the topics “Postural Control Of Stance And Gait” and “Otolith Function In Physiology And Pathophysiology”. Berlin is a traditional strong research site in neurotology. Hans SCHERER and Andy CLARKE (Charite Medical School, Benjamin Franklin Campus, Vest. Res. Labs) designed the experiments for NASA/ESA space missions here at the Free University. They established otolith diagnostics for the normal ENT patient population and deduced from gravity and microgravity research how otolith disorders influence balance control. Thomas LEMPERT (Schlosspark-Klinik Berlin) is a neurologist who has worked extensively on BPPV and migrainous vertigo. Our group at UKB Hospital (Dietmar BASTA, Arne ERNST) has dealt extensively with VEMPs, posttraumatic vertigo and vestibular rehabilitation (including prosthetics). This Special Issue provides an overview of neurotological research activities in Germany, Austria and Switzerland. In addition to the publications included in this issue, the following topics were presented: Sollner (Cambridge) reviewed already published material on the evolution of otoliths from a genetic and molecular biological point of view and demonstrated that crystal growth is determined by genetics and gravity. Wiener-Vacher (Paris) provided a systematic review of the development of postural control and otolith disorders in children and outlined diagnostic procedures in this age group. Straumann (Zurich) reported on the clinical symptoms of central otolith disorders. Bischoff (Zurich) presented data on the prevention of falls by vitamin D supplementation in the elderly. The papers included in this Special Issue have been peer-reviewed by the Journal of Vestibular Research. This review process has allowed the authors to update their presentations. The papers fall into three mini-chapters. “Physiology of balance control: effects of aging” is represented by two papers. Allum (Basel) reports on the influence of age and height on trunk sway during stance and gait to identify elderly fallers. Walther (Aachen) reviews structural alterations in older persons with imbalance at the level of the vestibular sensory cells and otoconia. The second topic, “Methods of testing otolith function”, is represented by three papers. Basta (Berlin) describes the methodology of VEMP testing in analyzing saccular function. Clarke (Berlin) provides insights into ocular torsion response to active head-roll during spaceflight missions of four subjects (up to 400 days in the orbit!). He shows that the torsional VOR is not just an evolutionary relic from the past, but a highly organized response to gravitational stimuli. Westhofen (Aachen) reports on the otolith-ocular reflex in Meniere’s patients before and after surgery. Finally, “Recent advances in vestibular rehabilitation” is repre-

Why do patients with PSP fall?

Patients with progressive supranuclear palsy (PSP) fall frequently, beginning early in the course of their disease. Abnormal vestibulospinal reflexes are suspected, but the angular vestibulo-ocular reflex, which is mediated by the labyrinthine semicircular canals, survives late into the course of the disease. To test the hypothesis that otolithic-mediated reflexes are abnormal in PSP. We tested otolith-ocular reflexes (the translational vestibulo-ocular reflex [tVOR]) during combined rotation-translation in nine patients with PSP and nine age-matched control subjects; subjects viewed far and near targets. We also tested click-induced otolith-spinal reflexes (vestibular-evoked myogenic potentials [VEMPs]) in 10 patients with PSP and 30 age-matched controls. All patients with PSP had small tVOR responses during near viewing that were, on average, only 12% of those of control subjects (p = 0.001). Patients with PSP also showed a reduction of the amplitude of VEMPs compared to control subjects (median [range]: 54.3 [16.8 to 214] vs 149 [11.6 to 466], p = 0.001). Taken together, these results indicate that abnormal otolith-mediated reflexes may be at least partly responsible for frequent falls in progressive supranuclear palsy, and deserve further study.

Adaptive neural mechanism for Listing's law revealed in patients with skew deviation caused by brainstem or cerebellar lesion.

Skew deviation is a vertical strabismus caused by damage to the otolithic-ocular reflex pathway and is associated with abnormal ocular torsion. This study was conducted to determine whether patients with skew deviation show the normal pattern of three-dimensional eye control called Listing's law, which specifies the eye's torsional angle as a function of its horizontal and vertical position. Ten patients with skew deviation caused by brain stem or cerebellar lesions and nine normal control subjects were studied. Patients with diplopia and neurologic symptoms less than 1 month in duration were designated as acute (n = 4) and those with longer duration were classified as chronic (n = 10). Serial recordings were made in the four patients with acute skew deviation. With the head immobile, subjects made saccades to a target that moved between straight ahead and eight eccentric positions, while wearing search coils. At each target position, fixation was maintained for 3 seconds before the next saccade. From the eye position data, the plane of best fit, referred to as Listing's plane, was fitted. Violations of Listing's law were quantified by computing the "thickness" of this plane, defined as the SD of the distances to the plane from the data points. Both the hypertropic and hypotropic eyes in patients with acute skew deviation violated Listing's and Donders' laws-that is, the eyes did not show one consistent angle of torsion in any given gaze direction, but rather an abnormally wide range of torsional angles. In contrast, each eye in patients with chronic skew deviation obeyed the laws. However, in chronic skew deviation, Listing's planes in both eyes had abnormal orientations. Patients with acute skew deviation violated Listing's law, whereas those with chronic skew deviation obeyed it, indicating that despite brain lesions, neural adaptation can restore Listing's law so that the neural linkage between horizontal, vertical, and torsional eye position remains intact. Violation of Listing's and Donders' laws during fixation arises primarily from torsional drifts, indicating that patients with acute skew deviation have unstable torsional gaze holding that is independent of their horizontal-vertical eye positions.

Vestibulo-ocular function in anxiety disorders

Previous studies of vestibulo-ocular function in patients with anxiety disorders have suggested a higher prevalence of peripheral vestibular dysfunction compared to control populations, especially in panic disorder with agoraphobia. Also, our recent companion studies have indicated abnormalities in postural control in patients with anxiety disorders who report a high degree of space and motion discomfort. The aim of the present study was to assess the VOR, including the semicircular canal-ocular reflex, the otolith-ocular reflex, and semicircular canal-otolith interaction, in a well-defined group of patients with anxiety disorders. The study included 72 patients with anxiety disorders (age 30.6 +/- 10.6 yrs; 60 (83.3% F) and 29 psychiatrically normal controls (age 35.0 +/minus; 11.6 yrs; 24 (82.8% F). 25 patients had panic disorder; 47 patients had non-panic anxiety. Patients were further categorized based on the presence (45 of 72) or absence (27 of 72) of height phobia and the presence (27 of 72) or absence (45 of 72) of excessive space and motion discomfort (SMD). Sinusoidal and constant velocity earth-vertical axis rotation (EVAR) was used to assess the semicircular canal-ocular reflex. Constant velocity off-vertical axis rotation (OVAR) was used to assess both the otolith-ocular reflex and static semicircular canal-otolith interaction. Sinusoidal OVAR was used to assess dynamic semicircular canal-otolith interaction. The eye movement response to rotation was measured using bitemporal electro-oculography. Results showed a significantly higher VOR gain and a significantly shorter VOR time constant in anxiety patients. The effect of anxiety on VOR gain was significantly greater in patients without SMD as compared to those with SMD. Anxiety patients without height phobia had a larger OVAR modulation. We postulate that in patients with anxiety, there is increased vestibular sensitivity and impaired velocity storage. Excessive SMD and height phobia seem to have a mitigating effect on abnormal vestibular sensitivity, possibly via a down-weighting of central vestibular pathways.

半規管―眼反射と耳石―眼反射の機能連関

Vestibulo-ocular reflex (VOR) generates smooth eye movements that are compensatory for head movements to ensure gaze stabilization during head rotations. VOR consists of the semicircular-ocular reflex (ScOR) and the otolith-ocular reflex (OOR). The ScOR induces eye movements that compensate for rotations of the head, whereas the OOR produces eye movements that compensate for linear head movements, so that visual images remain relatively steady on the retina.During normal visual-vestibular interaction, cooperation between the VOR and vision result in stabilization of the retinal image. Adaptive VOR recalibration occurs whether visual-vestibular mismatch arises through the manipulation of visual feedback during head movement or by lesion-induced modification of vestibular input. Current models of the VOR contain separate gain elements for the ScOR and the OOR.In this article, we describe our experiments to investigate the plasticity of the ScOR and OOR using OVAR and a linear sled to clarify visual-vestibular interaction. We also further addressed the relationship between adaptive change in the ScOR and the OOR.

Static Otolith-ocular Reflex Reflects Superior Oblique Muscle Disorder

To elucidate the action of static otolith-ocular reflex (sOOR) in patients with superior oblique palsy (SOP). Observational case series study. Compensatory ocular countertorsion produced by sOOR was analyzed in 12 patients with unilateral SOP and 11 normal subjects using a head-mounted measuring system. When the head was tilted laterally to the ipsilateral side, the mean ratio (%) of compensatory countertorsion of the paretic eye in SOP patients to the head-tilt angle was significantly decreased compared with that in normal subjects (7 +/- 6% for patients and 17 +/- 4% for normal subjects, P < .05). Mean ratio of compensatory countertorsion of the paretic eye in nine patients with superior oblique (SO) muscle atrophy was significantly lower than that in three patients with nonatrophy on tilting to the ipsilateral shoulder (6 +/- 3% for patients with atrophy and 14 +/- 6% for patients with nonatrophy, P < .05). sOOR reflects the anatomic disorder of the superior oblique muscle in SOP.

Treatment of the gravity dependence of downbeat nystagmus with 3,4-diaminopyridine

The authors examined the effect of 3,4-diaminopyridine (DAP) on the gravity-dependent (GD) vertical ocular drift component of downbeat nystagmus in 11 patients with idiopathic cerebellar ataxia. With the head tilted downward (45 degrees ), DAP reduced slow phase velocity (SPV) in 7 of 11 patients by 36%. Its efficacy correlated with the GD modulation. DAP minimizes the gravity-independent velocity bias and may improve deficient inhibitory cerebellar control on overacting otolith-ocular reflexes.

Utricular Dysfunction in Patients with Benign Paroxysmal Positional Vertigo

The objective of this study was to test the hypothesis that utricular function is impaired in patients with idiopathic benign paroxysmal positional vertigo. Prospective cohort study. Tertiary dizziness clinic and vestibular research laboratory. Twelve patients with unilateral idiopathic benign paroxysmal positional vertigo were examined 1 week and 1 month after successful treatment with positioning maneuvers and compared with 24 healthy subjects. None. Otolith function was assessed with estimation of the subjective visual vertical and analysis of the torsional otolith-ocular reflex. Unilateral stimulation of the utricle was performed on a rotator that allowed eccentric lateral displacement of the patient during earth-vertical rotation with constant velocity. The otolith-ocular reflex was recorded with three-dimensional video-oculography. There was no difference in the estimation of the subjective visual vertical between patients and controls. The peak-to-peak amplitude of the otolith-ocular reflex torsional eye position was smaller in patients than in the control group. The gain of the unilateral otolith-ocular reflex was reduced in patients on both sides on first testing. After several weeks, only the affected labyrinth showed a reduced otolith-ocular reflex gain. Our findings document otolith dysfunction in patients with idiopathic benign paroxysmal positional vertigo possibly secondary to degeneration of the utricular macula. This finding may account for the transient mild imbalance and dizziness that some patients with benign paroxysmal positional vertigo experience even after resolution of positional vertigo.

Treatment of the gravity-dependence of downbeat nystagmus with 3,4-diaminopyridine

The authors examined the effect of 3,4-diaminopyridine (DAP) on the gravity-dependent (GD) vertical ocular drift component of downbeat nystagmus in 11 patients with idiopathic cerebellar ataxia. With the head tilted downward (45°), DAP reduced slow phase velocity (SPV) in 7 of 11 patients by 36%. Its efficacy correlated with the GD modulation. DAP minimizes the gravity-independent velocity bias and may improve deficient inhibitory cerebellar control on overacting otolith–ocular reflexes.

Vestibular function in migraine-related dizziness: A pilot study

Migraine-related dizziness (MRD) refers to a disorder in which vestibular symptoms are an integral part of migraine symptomatology. The purpose of this study was to better define the pathophysiology of MRD, which is incompletely understood and to generate hypotheses regarding MRD by assessing the semicircular canal-ocular reflex, the otolith-ocular reflex, visual-vestibular interaction, vestibulo-spinal function, and visually induced postural sway. Subjects included five subjects with MRD, five subjects with migraine without dizziness, and five headache-free controls. Subjects with migraine were tested interictally. Results indicated that the mean gain of the semicircular canal-ocular reflex during both sinusoidal and constant velocity rotation was reduced in subjects with MRD. No changes were noted in the dynamics of the semicircular canal-ocular reflex. The otolith-ocular reflex, assessed with constant velocity OVAR, indicated that subjects with MRD showed a larger modulation component. No group differences were found in the bias component during constant velocity OVAR, nor in semicircular canal-otolith interaction or visual-vestibular interaction. Computerized dynamic posturography indicated that subjects with MRD demonstrated a surface-dependent pattern. Postural sway during optic flow indicated that subjects with MRD swayed more than the other subjects. We hypothesize that competing processes of serotonergic excitation and inhibition alter central vestibular pathways differently for semicircular canal vs. otolithic responses and for vestibulo-ocular vs. vestibulo-spinal pathways.

Otolithenfunktionstests - Ein differenziertes, qualitätsgesichertes Screeningsystem

More than 30% of all otogenic vestibular disorders are related to isolated macular dysfunction. Videooculographic examination techniques for the otolith-ocular reflex, e. g. by means of eccentric rotation tests, are not widely used in clinical routine as these put a considerable strain on technical and staff resources. Thus, there is a considerable risk of "false negative" classification of vertigo disorders being labelled as "non-otogenic". By means of vestibular-evoked myogenic potentials (VEMPs) and caloric irrigation in prone and supine position, several examination techniques for a side-related investigation of macula-induced vestibulo-ocular reflexes are available. The objective of this study is to compare and evaluate these techniques as screening tests. In 32 patients with vestibular disorders we performed investigations for VEMPs, eccentric rotation tests, as well as caloric irrigation for macular reaction in prone and supine position. In addition, we performed other audiologic and vestibular function tests which were complemented by the clinical course in order to differentiate each case between otogenic and non-otogenic vertigo with or without macular affection. The technical feasibility as well as patients' acceptance for VEMP testing is better than for eccentric rotation tests. The sensitivity index for VEMPs (89%) as well as for caloric irrigation in prone and supine position for macular examination (71%) is satisfactory. However, the specificity of VEMPs is inferior (53%) to eccentric rotation (100%). Both the examination for VEMPs as well as caloric macular testing in prone and supine position carry features which make them feasible for screening, even though these two procedures test for two different parts of the otolith system. However, to confirm a diagnosis and to set up a therapeutic concept for macular function disorders, eccentric rotation should be added.

Artificial gravity: A possible countermeasure for post-flight orthostatic intolerance

Four payload crewmembers were exposed to sustained linear acceleration in a centrifuge during the Neurolab (STS-90) flight. In contrast to previous studies, otolith–ocular reflexes were preserved during and after flight. This raised the possibility that artificial gravity may have acted as a countermeasure to the deconditioning of otolith–ocular reflexes. None of the astronauts who were centrifuged had orthostatic intolerance when tested with head-up passive tilt after flight. Thus, centrifugation may also have helped maintain post-flight hemodynamic responses to orthostasis by preserving the gain of the otolith–sympathetic reflex. A comparison with two fellow Neurolab orbiter crewmembers not exposed to artificial gravity provided some support for this hypothesis. One of the two had hemodynamic changes in response to post-flight tilt similar to orthostatically intolerant subjects from previous missions. More data is necessary to evaluate this hypothesis, but if it were proven correct, in-flight short-radius centrifugation may help counteract orthostatic intolerance after space flight.

August 24 Highlights

Lyons et al. assessed the surgical and hardware complications in 81 Parkinson patients undergoing subthalamic DBS. There were no deaths or permanent neurologic deficits. Complications included: one with hemorrhage, two systemic infections requiring removal, three infections requiring pulse generator removal, 10 misplaced leads, and 26 hardware complications. see page 612 Glasauer et al. compared VOR responses to head impulses in patients with downbeat nystagmus and in controls. No differences were found. Upward and downward VOR responses were symmetrical in patients, arguing against the hypothesis that DBN is caused by vestibular dysfunction. see page 621 Helmchen et al. showed that the potassium channel blocker 3, 4-diaminopyridine specifically improves the gravity-dependent component of downbeat nystagmus. This effect may be exerted on the deficient vestibulocerebellar inhibition of the physiologically overactive otolith-ocular reflex. see page 752 The editorial by Halmagyi and Leigh reviews the causes and likely mechanisms of downbeat nystagmus (DBN), as well as the causes of upbeat nystagmus, and notes that in perhaps half of …

空間識と可塑性（何が変わるか）

The vestibulo-ocular reflex (VOR) generates smooth eye movements that are compensatory for head movements to ensure gaze stabilization during head rotation. The VOR, which consists of semicircular-ocular reflex (ScOR) and otolith-ocular reflex (OOR), is adaptively controlled to correct VOR performance when visual-vestibular mismatch arises during head movement. Most studies have investigated horizontal ScOR gain adaptation after exposure to enhanced, reduced, or direction-reversed visual surround motion produced either by optical devices or by coupling altered visual surround motion with head movement in such a way as to reduce or eliminate retinal image slip during head movement. In natural head movement, not only the ScOR, but also the OOR must be used to keep the line of sight stationary in space. It remains unclear how human subjects combine input from the semicircular canals and otolith organs to establish spatial orientation. To investigate the synergy of the ScOR and the OOR, we examine the plasticity of the OOR using visual-vestibular interaction and the effect of adaptive plasticity in the OOR upon ScOR. We demonstrated a reason-ably consistent effect of adaptation of OOR sensitivity on the ScOR using a visual magnification paradigm. Our data suggest that the OOR and the ScOR partly share common neural pathways in such a way that a change in the synaptic efficacy of one pathway is accompanied by a change in the other. Recent data have also suggested the existence of a convergent neuron that receives input from both the semicircular canals and otolith organs in the cat. The role of a neural store that receives input from both the semicircular canals and the otolith organs to maintain a spatial orientation is discussed.

Otolith-ocular responses in patients with surgically confirmed unilateral peripheral vestibular loss

The chronic effects of unilateral peripheral vestibular loss (UPVL) are influenced by vestibular compensation. This study documents the balance-related symptoms and quantitative vestibular laboratory testing of 20 patients with surgically confirmed UPVL. Included are measures of the semicircular canal-ocular reflex, the otolith-ocular reflex, and both static and dynamic semicircular canal-otolith-interaction. This study differs from previous studies of patients with UPVL in that a large number of patients with surgically confirmed lesions were tested with three types of off-vertical axis rotation, several of the patients had anatomically preserved superior vestibular nerves, and self-perceived level of disability related to dizziness and imbalance were available. Results confirmed previously reported changes in the vestibulo-ocular reflex of patients with UPVL. Also, there was no apparent effect of anatomically preserving the superior vestibular nerve during surgical resection of vestibular schwannomas based on either subjective or objective measures of vestibular dysfunction. Further, there were no apparent correlations between subjective measures of dizziness and imbalance and objective measures of vestibulo-ocular function. These results have clinical implications for the management of patients with unilateral vestibular loss and provide insights into the process of vestibular compensation especially with respect to the otolith-ocular reflex.

耳石性眼反応の特徴―ステップ状側方直線加速度負荷による解析―

Lateral linear acceleration induces otolithic nystagmus and the otolith-ocular reflex (OOR). These response properties have been studied mostly by dynamic analysis using sinusoidal translation, and only a few reports are available so far with static analysis using step-mode acceleration, due to technical limitations. According to our studies using a linear accelerator with a period up to several seconds of step-mode lateral oscillation (Mori and Katayama, 1998; Katayama and Mori 2001), the direction of nystagmus is dependent on G-direction and directional preponderance (DP) of nystagmus elicitation is physiological. The slow cumulative eye-position (SCEP) curve in which the fast components are eliminated is saw-toothed in shape when lateral oscillation continues in a step mode, implying that the eye position, instead of the eye velocity, is controlled by stimulus velocity signals. The SCEP often accompanies a slow drift during the oscillation, and the slow-drift slope is positively correlated with DP: the steeper the slope, the larger the DP. The OOR velocity measured from the SCEP slope is symmetrical between G-directions when the slow drift is cancelled algebraically. Such symmetry in OOR velocity is in agreement with the previous reports (Gianna et al., 1997; Lempert et al., 1998 1999) using a short and single step-mode acceleration, suggesting that the slow drift is a component hidden behind the ordinary ocular movement and adjusted by the fast phase of nystagmus.

Human otolith–ocular reflexes during off-vertical axis rotation: effect of frequency on tilt–translation ambiguity and motion sickness

The purpose of this study was to examine how the modulation of tilt and translation otolith–ocular responses during constant velocity off-vertical axis rotation varies as a function of stimulus frequency. Eighteen human subjects were rotated in darkness about their longitudinal axis 30° off-vertical at stimulus frequencies between 0.05 and 0.8 Hz. The modulation of torsion decreased while the modulation of horizontal slow phase velocity (SPV) increased with increasing frequency. It is inferred that the ambiguity of otolith afferent information is greatest in the frequency region where tilt (torsion) and translational (horizontal SPV) otolith–ocular responses crossover. It is postulated that the previously demonstrated peak in motion sickness susceptibility during linear accelerations around 0.3 Hz is the result of frequency segregation of ambiguous otolith information being inadequate to distinguish between tilt and translation.

Orienting otolith-ocular reflexes in the rabbit during static and dynamic tilts and off-vertical axis rotation

Orienting otolith-ocular reflexes were assessed in rabbits using static tilt, off-vertical axis rotation (OVAR) and sinusoidal oscillation about earth-horizontal axes. In all paradigms, head pitch produced ocular counter-pitch and vergence, and head roll produced ocular counter-roll and conjugate yaw version. Thus, vergence and version are essential components of orienting reflexes along the naso-occipital and bitemporal axes. Vergence and version caused misalignment between the axes of eye and head movement during pitch and roll head movements. Semicircular canal input broadened the band-pass of these orienting reflexes, which would make them more appropriate when compensating for head movement during active motion.

Effect of aging on the otolith-ocular reflex

We assessed the influence of age on the otolith-ocular reflex and semicircular canal-otolith interaction. Healthy young (n=30) and healthy older (n=60) subjects were rotated about an earth vertical axis, and about a 30 degree off-vertical axis. Eye movements during and following rotation were recorded using electro-oculography. Results indicated that there were statistically significant changes in the otolith-ocular reflex and semicircular canal-otolith interaction as a function of age. The modulation component during off-vertical axis rotation (OVAR) was greater in the older group compard to the young adults, whereas the bias component was smaller with advanced age. The foreshortening of the vestibulo-ocular reflex time constant induced by post-rotatory head tilt following cessation of rotation was less prominent in the older group. There were no consistent changes in the semicircular canal-ocular reflex. Overall, response parameters showed more variability in the older subjects. We conclude that age related changes in the otolith-ocular reflex and semicircular canal-otolith interaction are a result primarily of a degradation of central vestibular processing of otolith signals rather than a decline of peripheral vestibular function.

Effect of light sleep on three-dimensional eye position in static roll and pitch

We examined three-dimensional eye positions in alertness and light sleep when monkeys were placed in different roll and pitch body orientations. In alertness, eye positions were confined to a fronto-parallel (Listing's) plane, torsional variability was small and static roll or pitch induced a torsional shift or vertical rotation of these planes. In light sleep, the planes rotated temporally by about 10°, torsional variability increased by a factor of two and the static otolith-ocular reflexes were reduced by about 70%. These data support the importance of a neural control of the thickness and orientation of Listing's plane, and suggest that part of the vestibular input underlying otolith-ocular reflexes depend on polysynaptic neural processing.