Otolith-ocular Reflex Research Articles

Binocular 3-D otolith-ocular reflexes: responses of chinchillas to natural and prosthetic stimulation after ototoxic injury and vestibular implantation.

The otolith end organs inform the brain about gravitational and linear accelerations, driving the otolith-ocular reflex (OOR) to stabilize the eyes during translational motion (e.g., moving forward without rotating) and head tilt with respect to gravity. We previously characterized OOR responses of normal chinchillas to whole body tilt and translation and to prosthetic electrical stimulation targeting the utricle and saccule via electrodes implanted in otherwise normal ears. Here we extend that work to examine OOR responses to tilt and translation stimuli after unilateral intratympanic gentamicin injection and to natural/mechanical and prosthetic/electrical stimulation delivered separately or in combination to animals with bilateral vestibular hypofunction after right ear intratympanic gentamicin injection followed by surgical disruption of the left labyrinth at the time of electrode implantation. Unilateral intratympanic gentamicin injection decreased natural OOR response magnitude to about half of normal, without markedly changing OOR response direction or symmetry. Subsequent surgical disruption of the contralateral labyrinth at the time of electrode implantation surgery further decreased OOR magnitude during natural stimulation, consistent with bimodal-bilateral otolith end organ hypofunction (ototoxic on the right ear, surgical on the left ear). Delivery of pulse frequency- or pulse amplitude-modulated prosthetic/electrical stimulation targeting the left utricle and saccule in phase with whole body tilt and translation motion stimuli yielded responses closer to normal than the deficient OOR responses of those same animals in response to head tilt and translation alone.NEW & NOTEWORTHY Previous studies to expand the scope of prosthetic stimulation of the otolith end organs showed that selective stimulation of the utricle and saccule is possible. This article further defines those possibilities by characterizing a diseased animal model and subsequently studying its responses to electrical stimulation alone and in combination with mechanical motion. We show that we can partially restore responses to tilt and translation in animals with unilateral gentamicin ototoxic injury and contralateral surgical disruption.

The Role of Different Afferent Systems in the Modulation of the Otolith-Ocular Reflex After Long-Term Space Flights.

BackgroundThe vestibular (otolith) function is highly suppressed during space flight (SF) and the study of these changes is very important for the safety of the space crew during SF missions. The vestibular function (particularly, otolith-ocular reflex–OOcR) in clinical and space medicine is studied using different methodologies. However, different methods and methodologies can influence the outcome results.ObjectiveThe current study addresses the question of whether the OOcR results obtained by different methods are different, and what the role is of the different afferent systems in the modulation of the OOcR.MethodsA total of 25 Russian cosmonauts voluntarily took part in our study. They are crewmembers of long duration space missions on the International Space Station (ISS). Cosmonauts were examined in pre- and post-flight “Sensory Adaptation” and “Gaze Spin” experiments, twice before (preflight) and three times after SF (post-flight). We used two different video oculography (VOG) systems for the recording of the OOcR obtained in each experiment.ResultsComparison of the two VOG systems didn’t result into significant and systematic differences in the OOcR measurements. Analysis of the static torsion otolith–ocular reflex (OOR), static torsion otolith–cervical–ocular reflex (OCOR) and static torsion otolith–ocular reflex during eccentric centrifugation (OOREC) shows that the OOREC results in a lower OOcR response compared to the OOR and OCOR (before flight and late post-flight). However, all OOcRs were significantly decreased in all cosmonauts early post-flight.ConclusionAnalysis of the results of ocular counter rolling (OCR) obtained by different methods (OOR, OCOR, and OOREC) showed that different afferent systems (tactile-proprioception, neck-cervical, visual and vestibular afferent input) have an impact on the OOcR.

Evolution of otolith-ocular reflex – the functional test of otolith and pharmacotherapy

Evolution of otolith-ocular reflex – the functional test of otolith and pharmacotherapy

Development of a new method for assessing otolith function in mice using three-dimensional binocular analysis of the otolith-ocular reflex

In the interaural direction, translational linear acceleration is loaded during lateral translational movement and gravitational acceleration is loaded during lateral tilting movement. These two types of acceleration induce eye movements via two kinds of otolith-ocular reflexes to compensate for movement and maintain clear vision: horizontal eye movement during translational movement, and torsional eye movement (torsion) during tilting movement. Although the two types of acceleration cannot be discriminated, the two otolith-ocular reflexes can distinguish them effectively. In the current study, we tested whether lateral-eyed mice exhibit both of these otolith-ocular reflexes. In addition, we propose a new index for assessing the otolith-ocular reflex in mice. During lateral translational movement, mice did not show appropriate horizontal eye movement, but exhibited unnecessary vertical torsion-like eye movement that compensated for the angle between the body axis and gravito-inertial acceleration (GIA; i.e., the sum of gravity and inertial force due to movement) by interpreting GIA as gravity. Using the new index (amplitude of vertical component of eye movement)/(angle between body axis and GIA), the mouse otolith-ocular reflex can be assessed without determining whether the otolith-ocular reflex is induced during translational movement or during tilting movement.

The Effect of Afferentation of Various Sensory Systems on the Otolith-Ocular Reflex in a Real and Simulated Weightlessness

Weightlessness can affect the vestibular function, primarily the otolith function, both directly due to the loss of gravitational influence and by eliminating the support and minimizing proprioceptive afferentation, influencing indirectly through the central integrative multisensory structures of the central nervous system (CNS), where the convergence of afferent signals of various sensory modality (primarily visual, vestibular, support and motor) occurs. All this prompted the study of the influence of various afferentations on the otolith-ocular reflex under the conditions of real and simulated weightlessness. Using the video oculography method, 58 Russian cosmonauts, members of long-term missions to the ISS (125–219 days, ~175 days on average), were examined by a static torsional otolith-cervical-ocular reflex (OCOR) with a head tilt to the shoulder at an angle of 30 deg, the otolith-ocular reflex (OOR) when the body is tilted at an angle of 30 deg, and the otolith-ocular reflex when exposed to centrifugal acceleration using a centrifuge (OORCF). Nine out of 58 cosmonauts were examined in microgravity (175 days) as part of the Virtual space experiment (Stage 1). The study of simulation of the spaceflight (SF) factors involved 30 subjects during five- or seven-day horizontal “dry” immersion (DI) and 12 subjects in 60-day head-down tilt (–8 deg) bed rest (BR). The procedure and the corresponding hardware and software used both in studies with the participation of cosmonauts and in model experiments were completely identical. In weightlessness, throughout the whole SF, all the cosmonauts surveyed had a significant OCOR decrease with the presence (from 11 to 55%, depending on the flight day) of the atypical (inversion or absence) otolith-ocular reflex. After SF, on days 1–4 of examination, 80% of the cosmonauts exhibited a significant OCOR/OOR decrease; 34% of the cosmonauts had atypical (inversion or absence of the otolith reflex) vestibular reactions, while no differences were found between OCOR and OOR. Statistically significant differences were found between the values ​of the OCOR/OOR and OORCF reflexes before and on days 4–5, 9–12 after SF. On days 2–3 after SF, no difference between OORCF and OCOR/OOR was observed. The return of the otolith reflex to the baseline took place only on day 9 after SF. The OCOR/OOR study on days 1–3 after DI showed that the otolith-ocular reflex in 47% of those examined was significantly reduced; in 13% of the subjects atypical reactions (absence or inversion of the reflex) were recorded. On days 4–6 after DI, OCOR/OOR returned to the baseline in all subjects. Analysis of OCOR/OOR after the BR experiment showed that only 14% of the surveyed had a significant decrease in OCOR/OOR on day 1 after the experiment. The atypical form of OCOR/OOR (inversion or complete absence of the otolith reflex) after BR was not revealed in contrast to the testers after DI. The results obtained demonstrated the influence of nonvestibular afferentation on the intensity of the otolith-ocular reflex and its dependence on other sensory inputs.

Clinical application of 3D-VOG analysis for quantitative evaluation of Otolith-Ocular reflex in the roll and pitch planes

Background Management of vestibular falls requires precise evaluation of otolithic function and gravity recognition. Tilt of the head in the roll plane causes ocular counter rolling (OCR) with a gain of 5–10%, which can be a quantitative parameter related to the otolith-ocular reflex (OOR) in that plane. However, the OOR in the pitch plane is indiscernible because of our ability to voluntarily gaze and pursue. 3 D eye movements and its Listing’s plane description can provide novel parameters with which to evaluate OOR, even in the pitch plane. Objectives To evaluate the utility of 3 D eye movement analysis in video oculography (VOG) as a quantitative parameter reflecting otolithic function during head movements associated with daily life. Materials and methods In healthy subjects, we analyzed the changes in 3 D eye movements and the Listing’s plane that occur with static gravitational modification. Results OOR during head tilt in the roll plane revealed that OCR amplitude had a saturating/peaked conformation and was not fitted by a sine curve. OOR in the pitch plane revealed anteroposterior leaning of the Listing’s plane. Conclusions These novel tools for minimally invasive evaluation of OOR in a clinical setting could potentially enable us to quantitatively evaluate peripheral static disequilibrium.

Vestibulo-Ocular Responses, Visual Field Dependence, and Motion Sickness in Aerobatic Pilots.

BACKGROUND: Aerobatic flight is a challenge for the vestibular system, which is likely to lead to adaptive changes in the vestibular responses of pilots. We investigated whether aerobatic pilots, as individuals who experience intense vestibular stimulation, present modifications of the vestibular-ocular reflex, motion sickness susceptibility and intensity, visual vertical estimation, and visual dependence as compared to normal volunteers.METHODS: To evaluate vestibulo-ocular reflexes, eye movements were recorded with videonystagmography while subjects were rotated on a rotatory chair with the axis of rotation being vertical (canal-ocular reflex) or inclined to 17° (otolith-ocular reflex). Motion sickness was evaluated after the rotatory test using the Graybiel diagnostic criteria. General motion sickness susceptibility and visual field dependence were also evaluated.RESULTS: Averaged data did not show significant difference in canal-ocular reflex and otolith ocular-reflex between groups. However, a significant asymmetry in otolith-driven ocular responses was found in pilots (CW 0.50 ± 1.21° · s-1 vs. CCW 1.59 ± 1.12° · s-1), though visual vertical estimation was not altered in pilots and both groups were found field independent. Pilots were generally less susceptible to motion sickness (MSSQ scores: 2.52 ± 5.59 vs. 13.5 ± 11.36) and less affected by the nauseogenic stimulation (Graybiel diagnostic criteria 3.36 ± 3.81 vs. 8.39 ± 7.01).DISCUSSION: We did not observe the expected habituation in the group of aerobatic pilots. However, there was a significant asymmetry in the otolith-driven ocular responses in pilots, but not in the controls, which may result from the asymmetry in piloting protocols.Kuldavletova O, Tanguy S, Denise P, Quarck G. Vestibulo-ocular responses, visual field dependence, and motion sickness in aerobatic pilots. Aerosp Med Hum Perform. 2020; 91(4):326-331.

Binocular 3D otolith-ocular reflexes: responses of normal chinchillas to tilt and translation.

Head rotation, translation, and tilt with respect to a gravitational field elicit reflexive eye movements that partially stabilize images of Earth-fixed objects on the retinas of humans and other vertebrates. Compared with the angular vestibulo-ocular reflex, responses to translation and tilt, collectively called the otolith-ocular reflex (OOR), are less completely characterized, typically smaller, generally disconjugate (different for the 2 eyes) and more complicated in their relationship to the natural stimuli that elicit them. We measured binocular 3-dimensional OOR responses of 6 alert normal chinchillas in darkness during whole body tilts around 16 Earth-horizontal axes and translations along 21 axes in horizontal, coronal, and sagittal planes. Ocular countertilt responses to 40-s whole body tilts about Earth-horizontal axes grew linearly with head tilt amplitude, but responses were disconjugate, with each eye's response greatest for whole body tilts about axes near the other eye's resting line of sight. OOR response magnitude during 1-Hz sinusoidal whole body translations along Earth-horizontal axes also grew with stimulus amplitude. Translational OOR responses were similarly disconjugate, with each eye's response greatest for whole body translations along its resting line of sight. Responses to Earth-horizontal translation were similar to those that would be expected for tilts that would cause a similar peak deviation of the gravitoinertial acceleration (GIA) vector with respect to the head, consistent with the "perceived tilt" model of the OOR. However, that model poorly fit responses to translations along non-Earth-horizontal axes and was insufficient to explain why responses are larger for the eye toward which the GIA vector deviates.NEW & NOTEWORTHY As the first in a pair of papers on Binocular 3D Otolith-Ocular Reflexes, this paper characterizes binocular 3D eye movements in normal chinchillas during tilts and translations. The eye movement responses were used to create a data set to fully define the normal otolith-ocular reflexes in chinchillas. This data set provides the foundation to use otolith-ocular reflexes to back-project direction and magnitude of eye movement to predict tilt axis as discussed in the companion paper.

Binocular 3D otolith-ocular reflexes: responses of chinchillas to prosthetic electrical stimulation targeting the utricle and saccule.

From animal experiments by Cohen and Suzuki et al. in the 1960s to the first-in-human clinical trials now in progress, prosthetic electrical stimulation targeting semicircular canal branches of the vestibular nerve has proven effective at driving directionally appropriate vestibulo-ocular reflex eye movements, postural responses, and perception. That work was considerably facilitated by the fact that all hair cells and primary afferent neurons in each canal have the same directional sensitivity to head rotation, the three canals' ampullary nerves are geometrically distinct from one another, and electrically evoked three-dimensional (3D) canal-ocular reflex responses approximate a simple vector sum of linearly independent components representing relative excitation of each of the three canals. In contrast, selective prosthetic stimulation of the utricle and saccule has been difficult to achieve, because hair cells and afferents with many different directional sensitivities are densely packed in those endorgans and the relationship between 3D otolith-ocular reflex responses and the natural and/or prosthetic stimuli that elicit them is more complex. As a result, controversy exists regarding whether selective, controllable stimulation of electrically evoked otolith-ocular reflexes (eeOOR) is possible. Using micromachined, planar arrays of electrodes implanted in the labyrinth, we quantified 3D, binocular eeOOR responses to prosthetic electrical stimulation targeting the utricle, saccule, and semicircular canals of alert chinchillas. Stimuli delivered via near-bipolar electrode pairs near the maculae elicited sustained ocular countertilt responses that grew reliably with pulse rate and pulse amplitude, varied in direction according to which stimulating electrode was employed, and exhibited temporal dynamics consistent with responses expected for isolated macular stimulation.NEW & NOTEWORTHY As the second in a pair of papers on Binocular 3D Otolith-Ocular Reflexes, this paper describes new planar electrode arrays and vestibular prosthesis architecture designed to target the three semicircular canals and the utricle and saccule. With this technological advancement, electrically evoked otolith-ocular reflexes due to stimulation via utricle- and saccule-targeted electrodes were recorded in chinchillas. Results demonstrate advances toward achieving selective stimulation of the utricle and saccule.

An app-based diary for vestibular disorders: The DizzyQuest

The otolith-collic and otolith-ocular reflexes of patients who experienced episodic tilting or translational sensations in the pitch plane without any other vestibular symptoms were assessed using cervical vestibular evoked myogenic potentials (cVEMP) and ocular vestibular evoked myogenic potentials (oVEMP). Eleven patients (4 men and 7 women, mean age = 40.4) were enrolled. All of the patients complained of episodic tilting or translational sensations in the pitch plane. Patients with a medical history of rotatory vertigo, loss of consciousness, head trauma, or symptoms of central nervous dysfunction or proprioceptive dysfunction and those who had been definitely diagnosed with a disease that causes disequilibrium were excluded. All 11 patients underwent cVEMP and caloric tests. Ten patients participated in the oVEMP tests. Seven of the 11 patients exhibited unilateral cVEMP absences, two displayed bilateral cVEMP absences, one demonstrated unilaterally decreased cVEMP, and one displayed normal cVEMP. Concerning oVEMP, 2 of the 10 patients showed unilateral oVEMP absences, 2 displayed bilateral oVEMP absences, 2 exhibited unilaterally decreased oVEMP, and 4 displayed normal oVEMP. All patients exhibited normal bilateral caloric responses. These findings were distinct from the results obtained for patients who experienced episodic lateral tilting sensations in previous studies. While most of the latter patients exhibited abnormal oVEMP, the patients in the present study tended to display abnormal cVEMP. These results suggest that patients with episodic tilting or translational sensations in the pitch plane suffer from saccular dysfunction. We propose “idiopathic otolithic vertigo” as a clinical entity and suggest that it is caused by idiopathic saccular dysfunction and/or utricular dysfunction.

Menstrual cycle effects on otolith-ocular reflex pathway

Introduction: Studies have shown morphological changes in the vestibule leading to alter the physiological changes during menstruation. And during the cycle, the level of hormones differs during different phases of the cycle. Hence, it is important to study the hormonal influences in the otolith-ocular pathways of females as the ocular vestibular evoked myogenic potentials (oVEMP) results might be interpreted wrongly if the different phase of the menstrual cycle affects the oVEMP results. The aim of the present study was to measure the changes in latency and amplitude of oVEMP test during three phases of the mensuration cycle. Materials and Methods: Twenty healthy females volunteers participated for the study and their otolith-ocular system was evaluated using oVEMP in three phases of the same cycle, i.e., menstruation phase (day 1–4), ovulation phase (day 12–17), and luteal phase (day 22–28). Results: oVEMP was present for all the participants in all the three phase of the menstrual cycle. For the obtained nonnormal data, nonparametric Freidman's Chi-square test was administered. The results showed no significant difference in latency or amplitude parameters of oVEMP across three recordings in participants, indicating that there was no significant effect of hormonal changes on oVEMPs recordings in females. Conclusions: It can be concluded that while assessing the vestibular system through an electrophysiological test like oVEMP, will not render differences in females based on their phases of menstruation cycles.

Veterans without mTBI are more likely to benefit from bilateral electrical vestibular stimulation

Damage to the vestibular system is often an unrecognized outcomeof mild Traumatic Brain Injury (mTBI). Ocular torsion can be used as a methodfor determining proper vestibular function of the otoliths with the applicationof imperceptible stochastic noise (SN) used to enhance the otolith‐ocular reflex. The goal of this work was to determine if Veterans with vestibular dysfunction withand without a history of mTBI would show a benefit from imperceptible SN.History of TBI was collected in 122 Veterans (86% male, age 53.7 ± 9.9 years). Thirty‐nine Veteransreported history of mTBI and 76 reported no history. Seven Veterans reported moderateTBI and were excluded from study analysis. History of mTBI was classified as areport of head injury immediately followed by loss of consciousness (less than 30 minutes) or any period of confusion or disorientation. Otolith dysfunctionscreening was performed on 102 Veterans and 41 Veterans returned to participatein repeated testing with and without SN. To assess otolith function andimprovement using imperceptible SN, ocular torsion was collected in response tosinusoidal tilt in the roll plane ± 20 degrees at a frequency of 0.03125 Hz (32sec/cycle). Ocular torsion (OT) gain was used to compare otolith function andimprovement over sham trials using SN.Veterans screened for otolith dysfunction showed similarrates between groups (58% Ctrl vs 57% mTBI). Veterans with no history of mTBIshowed a significant improvement in OCR with SN over those who reported historyof mTBI (mean improvement 21.3±21% Ctrl vs 1.8±19% mTBI, p=0.008). Statistical significance in OCR improvement remainedwhen adjusted for age (p=0.011). While no difference in mean age was observedbetween groups, Veterans with a history of mTBI showed a higher OCR gain withoutSN (0.09 ± 0.04 Ctrl vs 0.12 ± 0.05 mTBI, result not significant).These data show that while Veterans with a history ofmTBI demonstrate similar rates of vestibular impairment in otolith‐ocularreflexes, they may be less likely to benefit as a group from bilateralimperceptible electrical stimulation. Further investigation to clarify vestibular‐mediatedpathways of improvements using imperceptible SN are needed and evaluation of unilateraland canal deficits in adjusting for the use of SN may be a beneficialmodification for those that report a history of mTBI.Support or Funding InformationSupportedby DoD grant W81XWH‐14‐2‐0012This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Enhancing vestibular function in the elderly with imperceptible electrical stimulation

Age-related loss of vestibular function can result in decrements in gaze stabilization and increased fall risk in the elderly. This study was designed to see if low levels of electrical stochastic noise applied transcutaneously to the vestibular system can improve a gaze stabilization reflex in young and elderly subject groups. Ocular counter-rolling (OCR) using a video-based technique was obtained in 16 subjects during low frequency passive roll tilts. Consistent with previous studies, there was a significant reduction in OCR gains in the elderly compared to the young group. Imperceptible stochastic noise significantly increased OCR in the elderly (Mean 23%, CI: 17–35%). Increases in OCR gain were greatest for those with lowest baseline gain and were negligible in those with normal gain. Since stimulation was effective at low levels undetectable to subjects, stochastic noise may provide a new treatment alternative to enhance vestibular function, specifically otolith-ocular reflexes, in the elderly or patient populations with reduced otolith-ocular function.

Chapter 19 - Neuro-ophthalmologic assessment and investigations in children and adults with cerebellar diseases

In this chapter, we present the bedside assessment and laboratory tests that are available for the neuro-ophthalmologic evaluation of children and adults with cerebellar diseases. In the evaluation of a patient with cerebellar dysfunction, recognizing the pattern of ocular motor and / or vestibular impairment is often a key step to the correct diagnosis. The cerebellum is very important in processing a wide range of different eye movements, including angular vestibulo-ocular reflexes, otolith-ocular reflexes, fixation and gaze holding, smooth pursuit eye movements, saccadic eye movements, optokinetic response, ocular alignment, and vergence. Quantitative eye movement recording is now widely available in specialized clinics and medical practices, especially for testing the vestibulo-ocular reflexes. We describe the approach for assessing specific eye movements linked to cerebellar function, discuss appropriate eye movement laboratory tests, and summarize recent related research findings. In addition, for each laboratory test, we discuss its advantages, disadvantages, indications, and interpretations. Furthermore, we provide differential diagnoses for specific ocular motor and vestibular abnormalities such as slow saccades or impaired vestibulo-ocular reflexes.

Three-dimensional analysis of otolith-ocular reflex during eccentric rotation in humans

When a participant is rotated while displaced from the axis of rotation (eccentric rotation, ER), both rotational stimulation and linear acceleration are applied to the participant. As linear acceleration stimulates the otolith, the vestibulo-ocular reflex (VOR) caused by the otolith (linear VOR; lVOR) would be induced during ER. Ten participants were rotated sinusoidally at a maximum angular velocity of 50°/s and at frequencies of 0.1, 0.3, 0.5, and 0.7Hz. The radius of rotation during ER was 90cm. The participants sat on a chair at three different positions: on the axis (center rotation, CR), at 90cm backward from the axis (nose-in ER, NI-ER) and at 90cm forward from the axis (nose-out ER, NO-ER). Their eye movements during rotation were recorded and analyzed three-dimensionally. The VOR gain during NI-ER was lower at 0.5 and 0.7Hz, and that during NO-ER was higher at 0.3, 0.5, and 0.7Hz than during CR. These results indicate that lVOR actually worked at 0.5 and 0.7Hz during ER and that the enhancement and decline of the VOR gain relative to the VOR gain during CR was seen in humans. Thus, we suggest that otolith function can be assessed via rotational testing of NI-ER and NO-ER.

Translational otolith-ocular reflex during off-vertical axis rotation in humans

Two characteristics of otolith-ocular responses – linear vestibulo-ocular reflex and vergence – were examined during constant velocity off-vertical axis rotation (OVAR) in the dark. Sixteen subjects were rotated about their longitudinal axis when tilted 30° relative to the direction of gravity. Rotational velocities were 36 and 288/s corresponding to frequencies of 0.1 and 0.8Hz, respectively. Subjects were asked to imagine stationary targets located at 0.5m, 1m, and 2m in the straight-ahead direction. Binocular eye movements were recorded in the dark using infrared videography. The modulation of horizontal slow phase velocity during OVAR was larger at 0.8Hz than at 0.1Hz, and the modulation at the high frequency was larger for the near target than for the mid and far targets. These characteristics confirm that the horizontal slow phase velocity during yaw OVAR represents a translational otolith-ocular reflex in response to acceleration along the inter-aural axis that is dependent on imagined fixation distance.

Preserved otolith organ function in caspase-3-deficient mice with impaired horizontal semicircular canal function.

Genetically engineered mice are valuable models for elucidation of auditory and vestibular pathology. Our goal was to establish a comprehensive vestibular function testing system in mice using: (1) horizontal angular vestibulo-ocular reflex (hVOR) to evaluate semicircular canal function and (2) otolith-ocular reflex (OOR) to evaluate otolith organ function and to validate the system by characterizing mice with vestibular dysfunction. We used pseudo off-vertical axis rotation to induce an otolith-only stimulus using a custom-made centrifuge. For the OOR, horizontal slow-phase eye velocity and vertical eye position were evaluated as a function of acceleration. Using this system, we characterized hVOR and OOR in the caspase-3 (Casp3) mutant mice. Casp3 (-/-) mice had severely impaired hVOR gain, while Casp3 (+/-) mice had an intermediate response compared to WT mice. Evaluation of OOR revealed that at low-to-mid frequencies and stimulus intensity, Casp3 mutants and WT mice had similar responses. At higher frequencies and stimulus intensity, the Casp3 mutants displayed mildly reduced otolith organ-related responses. These findings suggest that the Casp3 gene is important for the proper function of the semicircular canals but less important for the otolith organ function.

The cerebellar nodulus: Perceptual and ocular processing of graviceptive input

Current concepts postulate a decisive role of the cerebellar nodulus in the processing of otolith input. We hypothesized that nodular lesions abolish otolith-perceptual integration, predicting alignment of perceived direction of earth vertical with the z-axis of the head and not with gravity. In an 80-year-old patient with acute heminodular infarction, the subjective visual vertical deviated contralesionally by -21.1° when the patient was upright. After subtracting this offset, perceived vertical closely matched the patient's head orientation when the patient was roll-tilted. Otolith-ocular reflexes remained normal. This is the first report on abolished earth verticality perception in heminodular stroke and underlines the importance of the nodulus in spatial orientation.

Recruitment properties and significance of short latency reflexes in neck and eye muscles evoked by brief lateral head accelerations.

Short lateral head accelerations were applied to investigate the recruitment properties of the reflexes underlying the earliest ocular and cervical electromyographic reflex responses to these disturbances. Components of both reflexes are vestibular dependent and have been termed “ocular vestibular evoked myogenic potentials” and “cervical vestibular evoked myogenic potentials”, respectively. Previous investigations using a unilateral vestibular stimulus have indicated that some but not all these vestibular-dependent reflexes show a simple power law relationship to stimulus intensity. In particular, crossed otolith-ocular reflexes showed evidence of an inflection separating two types of behaviour. The present stimulus acts bilaterally, and only the earliest crossed otolith-ocular reflex, previously shown to have a strictly unilateral origin, showed evidence of an inflection. Reflex changes in ocular torsion could, in principle, correct for the changes associated with translation for an elevated eye, but our findings indicated that the responses were consistent with previous reports of tilt-type reflexes. For the neck, both vestibular and segmental (muscle spindle) reflexes were evoked and followed power law relationships, without any clear separation in sensitivity. Our findings are consistent with previous evidence of “tilt-like” reflexes evoked by lateral acceleration and suggest that the departure from a power law occurs as a consequence of a unilateral crossed pathway. For the neck, responses to transients are likely to always consist of both vestibular and non-vestibular (segmental) components. Most of the translation-evoked ocular and cervical reflexes appear to follow power law relationship to stimulus amplitude over a physiological range.Electronic supplementary materialThe online version of this article (doi:10.1007/s00221-014-3980-3) contains supplementary material, which is available to authorized users.

Ocular vestibular evoked myogenic potentials to head tap and cervical vestibular evoked myogenic potentials to air-conducted sounds in isolated internuclear ophthalmoplegia

ObjectiveThe central pathways responsible for ocular vestibular evoked myogenic potentials (VEMPs) to forehead tapping remain to be determined. This study aimed to determine whether the medial longitudinal fasciculus (MLF) carries the signals for ocular VEMPs (oVEMPs) in response to this mode of stimulation. MethodsTwelve patients with isolated unilateral internuclear ophthalmoplegia (INO) due to brainstem infarction underwent evaluation of the ocular tilt reaction (ocular torsion and skew deviation), tilt of the subjective visual vertical (SVV), cervical VEMPs (cVEMPs) in response to tone burst sound, and oVEMPs induced by tapping the forehead. ResultsEight (67%) patients showed abnormal oVEMPs that included no wave formation (n=4) and decreased amplitude (n=3) in the lesion side, and bilaterally absent responses in the remaining patient. Furthermore, the patients showed diminished oVEMPs responses in the lesion side compared with normal side (6.0±5.6 vs. 11.7±5.5μV, paired t-test, p=0.001) and increased IADamp(%) of the oVEMPs compared with normal controls (43.6±41.2 vs. 9.1±6.2, t-test, p=0.018). In contrast, cVEMPs were abnormal in only three (25%) patients, decreased (n=2) or no response in the lesion side. Eleven (92%) patients showed contraversive ocular tilt reaction or SVV tilt. ConclusionPatients with INO frequently show impaired formation of ipsilesional oVEMPs in response to forehead tapping. The occasional abnormality and decreased amplitude of ipsilesional cVEMPs also suggest a modulatory pathway for the inhibitory sacculocollic reflex descending in the MLF. SignificanceThis study suggests that the MLF contains the fibers for the otolith-ocular reflex from the contralateral ear.