Linear Vestibulo-ocular Reflex Research Articles

New findings and pathophysiology in attitude control through vestibular interoception

Attitude control is associated with coordinated limb, body, head, and ocular movements through vestibular interoception. During straight walking, walking speed for velocities ranging from 1.2–1.8 m/s. Over this range of walking velocities, there is both translation and rotation of the head in the sagittal plane, reaching translational frequencies close to 2 Hz, peak vertical linear accelerations of 0.3–0.5 g, and peak pitch velocities of 15–22°/s. The magnitude and frequency of the pitch angular and vertical translational head movements are sufficient to activate both the angular and linear vestibulo-ocular (aVOR and lVOR) and vestibulo-collic (aVCR and lVCR) reflexes, which may play important roles in directing gaze and in stabilizing gait. In support of this, unilateral vestibular disease is associated with instability of gait, and astronauts, whose vestibular function has been adapted to microgravity, also experience difficulty when walking a curved path after flight. The purpose of this study was to infer a possible role for the vestibular interoception in producing head and eye movements in three dimensions as the body moves in space.

Impairment of vestibulo-collic reflex and linear vestibulo-ocular reflex in pediatric-onset multiple sclerosis patients

ObjectivesThis study aimed to examine the vestibulo-collic reflex (VCR) and linear vestibulo-ocular reflex (lVOR) and their correlation with brain lesions in pediatric-onset multiple sclerosis (POMS). MethodsThe study group consisted of 17 patients (34 ears) with POMS (mean age 18.73 ± 2.02, mean age at disease onset 14.64 ± 1.36 years), and the control group included 11 age-matched healthy subjects (22 ears). Ocular and cervical Vestibular Evoked Myogenic Potentials (oVEMP and cVEMP) were performed to assess IVOR and VCR pathways. Magnetic Resonance Imaging was evaluated in the study group. ResultsIn the POMS group, 47.05 % of oVEMPs and 17.64 % of the cVEMPs were abnormal, while all VEMPs were normal in the control group. The oVEMP amplitude was associated with infratentorial lesion volume (r = −0.459, p = 0.01) and total lesion volume of the brainstem and cerebellum (r = −0.450, p = 0.01). The cVEMP asymmetry ratio was correlated with the deep white matter lesion volume (r = 0.683, p < 0.001). The MVEMP scores were found to correlate only with lesion volumes in the cerebellum (r = 0.488, p = 0.04) and infratentorial region (r = 0.573, p = 0.01). ConclusionsOcular and cervical VEMP abnormalities confirm that lVOR and VCR pathways may be affected in early POMS. SignificanceRoutine use of the VEMP test, especially the oVEMP test is recommended as a useful tool in the follow-up of POMS patients.

Vergence increases the amplitude of lateral ocular vestibular evoked myogenic potentials.

The angular and linear vestibulo-ocular reflex responses are greater when viewing near targets to compensate for the relatively larger translation of the eyes with respect to the target. Our aim was to measure vestibular evoked myogenic potentials using a lateral ocular electrode montage (oVEMP) with a laterally applied stimulus using a mini-shaker during both far- and near-viewing (vergence) distances to determine whether vergence affects the oVEMP response as it does the semicircular canal vestibulo-ocular reflex response. Our results show that during vergence, the p1 and n1-p1 amplitude of the lateral oVEMP response increases significantly, whereas the latencies do not change significantly. We suggest that the physiological basis for this vergence-mediated amplitude increase in potentials may be the same as those already documented using transient linear head accelerations. Our data also suggest that irregular vestibular afferents are likely mediating the vergence-mediated gain increase during linear head accelerations because only irregular afferents are stimulated during short, transient 500Hz stimuli.

Effects of viewing distance on ocular vestibular evoked myogenic potentials (oVEMPs) for air- and bone-conducted stimuli at multiple sites.

The ocular vestibular evoked myogenic potential is otolith-dependent and has been suggested to be a manifestation of the linear vestibulo-ocular reflex (L-VOR). A characteristic feature of the translational LVOR (t-LVOR) is its dependence on the distance of a target. To assess if viewing distance affects amplitude and latency properties of the ocular vestibular evoked myogenic potential (oVEMPs). Bone- and air-conducted (BC and AC) stimuli were used to evoke oVEMPs in 10 healthy subjects. BC stimuli consisted of impulsive accelerations applied at the mastoids, AFz, Oz and Iz. AC stimuli consisted of 500 Hz tones delivered unilaterally to each ear. Target distances of 40 cm (near), 190 cm (intermediate) and 340 cm (far) were used for all stimuli. The largest amplitude oVEMP was obtained from Iz and the latency for AFz was shorter than for BC stimulation at other sites. We found no significant effect of target distance on oVEMP amplitudes for any of the stimuli used. There was a small but significant effect on latency with the nearest target having a longer latency (overall 12.4 ms vs 12.0 ms for the 2 more distant sites). Previously reported differences between latencies and stimulus sites for midline BC stimulation were confirmed. Target distance had no significant effect on oVEMP amplitude, which suggests it is not modified like other components of the t-LVOR.

Effects of cochlear implants on otolith function as evaluated by vestibulo-ocular reflex and vestibular evoked myogenic potentials

ObjectiveThe aim of this study was to investigate whether the insertion of an implant into the cochlea is accompanied by a deterioration in otolith function. Cervical and ocular vestibular evoked myogenic potentials (cVEMP and oVEMP) and linear vestibulo-ocular reflex (lVOR) during eccentric rotation were assessed before and after cochlear implantation (CI) to evaluate otolith function. MethodsTwelve patients with bilateral severe sensorineural hearing loss who had undergone CI surgery in our hospital between May 2016 and November 2017 were included in this study. cVEMP and oVEMP were assessed using the asymmetry ratio (AR), calculated with the following formula: [(peak-to-peak amplitude calculated as the sum of the p13 and n23 amplitudes in the non-operated side) − (that in the operated side)]/[(that in the non-operated side) + (that in the operated side)]. The ratio of VOR gain during eccentric rotation against VOR gain during center rotation was used to assess lVOR. For eccentric rotation, patients were rotated while displaced from the axis of rotation. At the same time, linear acceleration stimulated the utricle and induced lVOR. All patients underwent cVEMP and oVEMP tests and center and eccentric rotation tests before and about 30days after CI surgery. ResultsThree patients with absent cVEMP responses before surgery were excluded, leaving pre-surgery cVEMP results for 9/12 patients. In five of these patients, the AR of cVEMP increased after CI, indicating that saccular function, as evaluated by cVEMP, did not deteriorate significantly postoperatively. One patient with an absent oVEMP response before CI was excluded, leaving pre-surgery oVEMP results for 11/12 patients. In 10 of these patients, the AR of oVEMP increased after CI surgery, indicating that utricular function, as evaluated by oVEMP, deteriorated significantly postoperatively. However, because the ratio of VOR gain during eccentric rotation against VOR gain during center rotation did not become worse after CI, utricular function, as evaluated by lVOR, did not deteriorate significantly postoperatively. Symptoms of vertigo became worse after CI in two of the 12 patients. ConclusionCI does not cause a deterioration in saccular function, as evaluated by cVEMP. Although CI does cause a deterioration in utricular function in oVEMP tests, this is not consistent in lVOR tests. These results indicate that CI causes a slight deterioration in utricular function that is insufficient to cause vertigo or deterioration of lVOR.

Strategies for Gaze Stabilization Critically Depend on Locomotor Speed

Locomotion involves complex combinations of translational and rotational head movements. For gaze stability, this necessitates the interplay of angular and linear vestibulo-ocular reflexes (VOR) as well as the integration of visual feedback about the desired viewing distance. Furthermore, gaze stabilizing systems must be able to cope with vast differences in head motion brought about by changing locomotor speeds and patterns (walking vs. running). The present study investigated horizontal and vertical angular VOR (aVOR) and linear gaze stabilization (lGS) as well as compensation for linear head movements by angular counter rotation of the head during treadmill walking and running at different velocities (0.4 to 2.4 m/s) while fixating either a close (0.5 m) or distant (2.0 m) target. In the horizontal plane, the aVOR predominated throughout all locomotor speeds, whereas the compensation of linear translations was highly variable and generally insufficient. In contrast, in the vertical plane, eye and angular head motion steadily became more in phase with increasing locomotor speed, which served to optimize linear motion compensation. Furthermore, the timing of the vertical aVOR became more automated and independent of visual feedback during faster locomotion. Thus, horizontal and vertical gaze stabilization strategies appear to be considerably different. Whereas horizontal gaze control is likely governed by passive sensorimotor reflexes throughout all locomotor speeds, vertical gaze stabilization switches to an automated feed-forward control at faster locomotion. This switch is presumably driven by efference copies from spinal locomotor commands that were previously shown to govern gaze stabilization in animal models during stereotypic locomotion.

Three-dimensional analysis of the vestibulo-ocular reflex and the ability to distinguish the direction of centripetal acceleration in humans during eccentric rotation with the right ear facing downwards

This study was conducted to evaluate the linear vestibulo-ocular reflex (lVOR) mediated by the saccule, and to investigate the relationship between the lVOR and the ability to distinguish the direction of centripetal acceleration during centric and eccentric rotation. Participants sat on a chair in darkness, with the right ear facing downwards, either directly above the center of rotation, or with their nose out, nose in, right shoulder out, or left shoulder out against the center of rotation (eccentric rotation). Participants were given no information about the chair position, and were rotated sinusoidally at 0.1–0.7 Hz. Three-dimensional eye movements during rotation were analyzed. Participants were asked to describe the position of the chair after rotation. Correctly reporting the five possible chair positions requires recognition of the direction of centripetal acceleration. We analyzed the rate of correct answers to assess participants’ ability to identify the direction of centripetal acceleration. lVOR mediated by the saccule was observed only at high rotational frequencies. The rate of correct answers was higher at high rotational frequencies than that at low rotational frequencies. These results indicate that high rotational frequency is important for both lVOR mediated by the saccule and distinguishing the direction of centripetal acceleration.

An Assay for Systematically Quantifying the Vestibulo-Ocular Reflex to Assess Vestibular Function in Zebrafish Larvae.

Zebrafish (Danio rerio) larvae are widely used to study otic functions because they possess all five typical vertebrate senses including hearing and balance. Powerful genetic tools and the transparent body of the embryo and larva also make zebrafish a unique vertebrate model to study otic development. Due to its small larval size and moisture requirement during experiments, accurately acquiring the vestibulo-ocular reflex (VOR) of zebrafish larva is challenging. In this report, a new VOR testing device has been developed for quantifying linear VOR (LVOR) in zebrafish larva, evoked by the head motion about the earth horizontal axis. The system has a newly designed larva-shaped chamber, by which live fish can be steadily held without anesthesia, and the system is more compact and easier to use than its predecessors. To demonstrate the efficacy of the system, the LVORs in wild-type (WT), dlx3b and dlx4b morphant zebrafish larvae were measured and the results showed that LVOR amplitudes were consistent with the morphological changes of otoliths induced by morpholino oligonucleotides (MO). Our study represents an important advance to obtain VOR and predict the vestibular conditions in zebrafish.

P118. Speed- and phase-dependent suppression of downbeat nystagmus during locomotion

Downbeat nystagmus (DBN) is the most common form of acquired fixation nystagmus. Patients typically suffer from oscillopsia and postural instability. Postural symptoms are known to improve during walking, in particular at fast speeds (Schniepp et al., 2014); however, it is unknown whether locomotion also influences ocular motor symptoms in these patients. We thus investigated the frequency and timing of DBN occurrence during standing and walking at different speeds in patients with DBN. Eye movements of DBN patients with clear central-gaze nystagmus were recorded using video-oculography during standing as well as treadmill walking at individual slow, preferred and fast speeds. Subjects were instructed to fixate on a target straight in front of them at 2 m distance. We analyzed the frequency and timing of occurrence of compensatory quick-phases (downbeats) throughout the gait cycle as well as the angular and linear components of the vestibulo-ocular-reflex (VOR) to assess general gaze stabilization performance during walking in these patients. Results were compared to healthy controls. Compared to rest, slow walking significantly lowered the frequency of DBN occurrence in all patients. With increasing walking speed, DBN frequency was further reduced and in some subjects even fully suppressed during fast walking. In addition, DBN events predominantly occurred at the start of the swing phase, indicating that DBN occurrence is phase-coupled to distinct periods of the gait cycle. Whereas angular VOR gains of patients during walking were comparable to those of healthy subjects, linear VOR components were found to be significantly decreased. DBN ocular-motor symptoms improve during walking, in particular at fast speeds, indicating a speed-dependent re-weighting of the involved vestibulo-cerebellar pathways during locomotion. In addition, compensatory quick-phase eye movements (downbeats) most frequently occur during distinct phases of the gait cycle, suggesting that a phase-coupled locomotor feedback such as spinal motor efference copies influences the brain networks associated with downbeat nystagmus. Notable deficits in compensating linear head motion during walking indicate impairments in pathways processing otolithic inputs, despite an intact integration of vestibular cues from the semicircular canals (Glasauer et al., 2004).

Location and phase effects for ocular and cervical vestibular-evoked myogenic potentials evoked by bone-conducted stimuli at midline skull sites.

Our object was to investigate the effect of location and phase on the properties of oVEMPs and cVEMPs evoked by two bone conducted (BC) stimuli, 500 Hz and an impulsive stimulus for midline skull sites from Nz to Iz, in normal volunteers. Compressive and rarefactive onset phases were used and the induced linear and rotational accelerations measured. We confirmed our previous finding of marked changes in the polarity of oVEMPs with location. For cVEMPs using the 500Hz stimulus there were few changes with location or phase, but the impulsive stimulus showed clear phase-related changes at several locations, with the shortest latencies occurring with compressive stimuli at AFz and Fz and the largest amplitudes at Iz. For oVEMPs, both stimuli showed clear effects of phase, with the shortest latencies with compressive stimuli at AFz and Fz and with the largest negativity at Oz or Iz. Whereas the effectiveness at Iz is consistent with a role in the linear VOR, the inversion of polarity and shorter latency around AFz and Fz is not and could not be explained by changes in acceleration of the head. The latency for BC 500Hz oVEMPs for AFz was the same as that for air-conducted (AC) stimuli. We suggest that whereas BC stimuli at most sites work through displacement of the otolith membrane, BC oVEMPs evoked at AFz and Fz may work through a direct action on utricular hair cells. Our findings have implications for clinical testing of VEMPs using midline BC stimuli. NEW & NOTEWORTHY We investigated VEMPs evoked from multiple midline skull sites. Large oVEMP responses were obtained with compressive stimuli at Iz, consistent with a role in the linear VOR, but we also showed inversion of polarity and the shortest latency for stimuli given at AFz and Fz. We propose that BC stimuli given at AFz and Fz may have a direct effect on otolith hair cells, whereas at other sites they work through displacement of the otolith membrane.

Three-dimensional analysis of linear vestibulo-ocular reflex in humans during eccentric rotation while facing downwards.

When participants undergo eccentric rotation (ER), i.e., they are rotated while displaced from the axis of rotation, they undergo both rotational stimulation and linear acceleration, which induces both the angular vestibulo-ocular reflex (aVOR) and linear VOR (lVOR). During ER, the lVOR induced by tangential linear acceleration enhances the eye movement induced by aVOR. In this study, we attempted to measure aVOR and lVOR separately, while participants underwent ER while facing the ground in a dark room. We analyzed three-dimensional eye movements using a video-oculography system. The participants sat on the ER chair either directly above the center of rotation, or with their head out, head in, right ear out, or left ear out against the center of rotation. Under these conditions, the rotational axis of the eye was perpendicular to the ground for rotational stimulation (aVOR), and the axis was parallel to the ground for linear stimulation (lVOR). Thus, measured eye movements could be separated into these two components. At 0.1 and 0.3Hz rotation, we observed aVOR but not lVOR. However, when the stimulation frequency was above 0.5Hz, we observed both aVOR and lVOR. These data indicate that lVOR is activated when the stimulation frequency is above 0.5Hz. We conclude that it is possible to separately analyze aVOR and lVOR, and to simultaneously assess the function of aVOR and lVOR by analyzing eye movements induced when participants undergo ER above 0.5Hz while facing the ground.

Assessment of endolymphatic hydrops and otolith function in patients with Ménière's disease.

Ménière's disease is associated with hydrops of the inner ear endolymphatic space, and histopathologically, the cochlea and vestibule are usually involved. We used gadolinium-enhanced magnetic resonance imaging and measured cervical and ocular vestibular evoked myogenic potentials and the gain in the utricular induced linear vestibulo-ocular reflex to test the hypothesis that vestibular hydrops in Ménière's disease patients is associated with otolith organ dysfunction. We evaluated 21 patients diagnosed with unilateral definitive Ménière's disease using gadolinium magnetic resonance imaging to detect endolymphatic hydrops in the cochlea and vestibule. Cervical and ocular vestibular evoked myogenic potentials and the gain in utricular induced linear vestibulo-ocular reflex during eccentric rotation were measured to assess otolith organ function. For eccentric rotation, patients were rotated while displaced from the axis of rotation, while linear acceleration stimulated the utricle and induced the vestibulo-ocular reflex. Magnetic resonance imaging revealed vestibular hydrops in 14 of 20 patients (70%). Among the 14 patients, ten (71%) had abnormal cervical and three (21%) had abnormal ocular vestibular evoked myogenic potentials. Four patients (4/21, 19%) had abnormal linear vestibulo-ocular reflexes, three of whom also had abnormal ocular vestibular evoked myogenic potentials. Overall, 16 of 17 patients had normal linear vestibulo-ocular reflexes and normal ocular vestibular evoked myogenic potentials. Vestibular endolymphatic hydrops in Ménière's disease patients caused otolith organ dysfunction, mainly in the saccule. The number of Ménière's disease patients with abnormal ocular vestibular evoked myogenic potentials was low (19%), and they also had abnormal utricular induced linear 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.

Vestibular examinations in apogeotropic positional nystagmus caused by cerebellar tumor

Horizontal, direction changing apogeotropic positional nystagmus (HAPN) is known to be associated with cerebellar lesions [1]. However, the pathophysiologic mechanism of cerebellar HAPN is unknown. We encountered a patient with a metastatic cerebellar tumor who presented with HAPN that disappeared after tumorectomy. Hyperactive vestibular reflexes, indicated by the results of electrophysiologic examinations, might have been the mechanism underlying the HAPN in this patient. A 70-year-old woman with a 2-month history of progressive dizziness and difficulty in walking was admitted to our hospital. She presented with truncal ataxia and HAPN but no other neurologic or neuroophthalmologic abnormalities. Contrast brain MRI revealed a well-enhanced cerebellar tumor. Because chest X-ray and CT showed a left lung tumor suggestive of lung cancer, a cerebellar metastasis was diagnosed. The cerebellar tumor was removed surgically 10 days after the patient’s admission. Pathologic examination of the surgical specimen revealed adenocarcinoma. After the tumorectomy, the HAPN was fully resolved, and the truncal ataxia was improved. The horizontal angular vestibulo-ocular reflex (A-VOR), cervical vestibular-evoked myogenic potential (C-VEMP), and ocular vestibular-evoked myogenic potential (O-VEMP) were evaluated before (when the HAPN was present) and 10 days after tumorectomy (when the HAPN had disappeared). A-VORs were recorded in darkness by means of a video-oculography-basedVORrecording and analysis system (IRN-2, Morita Mfg. Corp., Kyoto, Japan), with the patient seated on a rotating armchair with a headrest [2]. The chair was rotatedmanually in sinusoidal fashion for 20 s (frequency 0.5–0.75 Hz, amplitude 20 ) [2]. VOR gain, i.e., the eye velocity to head velocity ratio, was analyzed. C-VEMP was recorded from the tonically contracting ipsilateral sternocleidomastoid muscle during monaural stimulation with 105-dB clicks or short tone bursts (MEB 2312 testing system, Nihon Kohden, Tokyo, Japan; bandwidth 20–2,000 Hz, 200 averaged signals). Latencies of the first positive wave (p13) and second negative wave (n23) and peak-to-peak p13–n23 amplitude were measured. O-VEMP was recorded from the lower eyelids (inferior oblique muscles) during stimulation with 105 dB clicks or short tone bursts (MEB 2312, Nihon Kohden, Tokyo, Japan; bandwidth 20–2,000 Hz, 200 averaged signals). The patient was instructed to continue looking straight ahead and upward 30 . Because O-VEMP was not adequately elicited by monaural stimulation, binaural sound stimulation was applied. Latencies of the first negative wave (n1) and second positive wave (p1) and peak-to-peak n1–p1 amplitude were measured. Absolute A-VOR gains were reduced in both directions after the tumorectomy (Table 1). Cand O-VEMP amplitudes were also reduced on almost all recordings after tumorectomy (Table 1). Latencies of Cand O-VEMPs did not change. A-VOR is mediated by a semicircular-ocular pathway. C-VEMP reflects the vertical linear vestibulo-ocular reflex Electronic supplementary material The online version of this article (doi:10.1007/s10072-015-2086-4) contains supplementary material, which is available to authorized users.

Dynamic characteristics of otolith ocular response during counter rotation about dual yaw axes in mice

The central vestibular system plays an important role in higher neural functions such as self-motion perception and spatial orientation. Its ability to store head angular velocity is called velocity storage mechanism (VSM), which has been thoroughly investigated across a wide range of species. However, little is known about the mouse VSM, because the mouse lacks typical ocular responses such as optokinetic after nystagmus or a dominant time constant of vestibulo-ocular reflex for which the VSM is critical. Experiments were conducted to examine the otolith-driven eye movements related to the VSM and verify its characteristics in mice. We used a novel approach to generate a similar rotating vector as a traditional off-vertical axis rotation (OVAR) but with a larger resultant gravito-inertial force (>1g) by using counter rotation centrifugation. Similar to results previously described in other animals during OVAR, two components of eye movements were induced, i.e. a sinusoidal modulatory eye movement (modulation component) on which a unidirectional nystagmus (bias component) was superimposed. Each response is considered to derive from different mechanisms; modulations arise predominantly through linear vestibulo-ocular reflex, whereas for the bias, the VSM is responsible. Data indicate that the mouse also has a well-developed vestibular system through otoliths inputs, showing its highly conserved nature across mammalian species. On the other hand, to reach a plateau state of bias, a higher frequency rotation or a larger gravito-inertial force was considered to be necessary than other larger animals. Compared with modulation, the bias had a more variable profile, suggesting an inherent complexity of higher-order neural processes in the brain. Our data provide the basis for further study of the central vestibular system in mice, however, the underlying individual variability should be taken into consideration.

Dynamic visual acuity (DVA) during locomotion for targets at near and far distances: Effects of aging, walking speed and head-trunk coupling

This study examined effects of aging, head-trunk coupling (HTcoupling) and walking speed on dynamic visual acuity (DVA) at near and far viewing distances. Ten healthy participants were recruited in 3 groups; young: 20-33 years, Older1: 65-74 years, Older2: 75-85 years. The binocular DVA was measured while walking on a treadmill at 0.75 and 1.5 m/s speeds. The optotype display was placed at 0.5 m for NearDVA and at 3.0 m for FarDVA. On randomly selected trials, HTcoupling was achieved by using a collar. A mix-factor ANOVA (age-group x HTcoupling x speed) was performed separately for the Near and FarDVA. NearDVA declined with HTcoupling (p=0.021). Additionally, NearDVA worsened at the faster speed (p< 0.001). At 1.5 m/s speed the differences between Young and Older2 groups were significant (p=0.012) and those between Older1 and Older2 were marginal (p=0.085). FarDVA declined at the faster speed (p< 0.001) with no effect of HTcoupling or age-group. NearDVA is more sensitive to normal aging process. These age-related deficits become more apparent at higher walking speeds. Effect of HTcoupling on NearDVA suggests a possible additive effect of insufficient dampening of the vertical movement of the overall head-trunk complex and inability of the linear vestibulo-ocular reflex to compensate for the consequent high discrepancy.

Tests of linearity in the responses of eye-movement-sensitive vestibular neurons to sinusoidal yaw rotation.

The rotational vestibulo-ocular reflex in primates is linear and stabilizes gaze in space over a large range of head movements. Best evidence suggests that position-vestibular-pause (PVP) and eye-head velocity (EHV) neurons in the vestibular nuclei are the primary mediators of vestibulo-ocular reflexes for rotational head movements, yet the linearity of these neurons has not been extensively tested. The current study was undertaken to understand how varying magnitudes of yaw rotation are coded in these neurons. Sixty-six PVP and 41 EHV neurons in the rostral vestibular nuclei of 7 awake rhesus macaques were recorded over a range of frequencies (0.1 to 2 Hz) and peak velocities (7.5 to 210°/s at 0.5 Hz). The sensitivity (gain) of the neurons decreased with increasing peak velocity of rotation for all PVP neurons and EHV neurons sensitive to ipsilateral rotation (type I). The sensitivity of contralateral rotation-sensitive (type II) EHV neurons did not significantly decrease with increasing peak velocity. These data show that, like non-eye-movement-related vestibular nuclear neurons that are believed to mediate nonlinear vestibular functions, PVP neurons involved in the linear vestibulo-ocular reflex also behave in a nonlinear fashion. Similar to other sensory nuclei, the magnitude of the vestibular stimulus is not linearly coded by the responses of vestibular neurons; rather, amplitude compression extends the dynamic range of PVP and type I EHV vestibular neurons.

The linear vestibulo-ocular reflex, locomotion and falls in neurological disorders

During locomotion, head perturbations, consisting of rotations and translations (linear movements), occur with predominant frequencies of 0.5-5.0 Hz. The vestibular reflexes act at short latency to safeguard clear vision and stable posture during locomotion. Much is known about the angular vestibulo-ocular reflex (aVOR) in response to head rotations, which depend on the semicircular canals of the vestibular labyrinth. However, the means to test reliably the linear or translational vestibulo-ocular reflex (tVOR), which depends on the otolithic organs, has only become available more recently. We used a moving platform to translate normal human subjects vertically at frequencies similar to those occurring during locomotion, under ambient illumination. Our findings suggested that, whereas aVOR is concerned with stabilizing images of visual targets on the retina to optimize visual acuity, tVOR seems best suited to minimize retinal image motion between objects lying in different depth planes, in order to optimize motion parallax information. We then asked whether the tVOR functioned abnormally in patients with two neurological disorders that often cause falls: progressive supranuclear palsy (PSP) and cerebellar ataxia. We found that patients with PSP cannot adjust tVOR responses appropriately during viewing of near objects, nor converge their eyes. Vestibular-evoked myogenic potentials (VEMPs), an otolith-spinal reflex, are also impaired in PSP patients. Patients with cerebellar ataxia also lack the ability to adjust tVOR for near viewing, even though they may be able to converge. Taken together, our studies suggest that abnormal otolithic vestibular reflexes contribute to postural instability in PSP and cerebellar ataxia, and deserve further investigation.

The disturbance of gaze in progressive supranuclear palsy: implications for pathogenesis.

Progressive supranuclear palsy (PSP) is a disease of later life that is currently regarded as a form of neurodegenerative tauopathy. Disturbance of gaze is a cardinal clinical feature of PSP that often helps clinicians to establish the diagnosis. Since the neurobiology of gaze control is now well understood, it is possible to use eye movements as investigational tools to understand aspects of the pathogenesis of PSP. In this review, we summarize each disorder of gaze control that occurs in PSP, drawing on our studies of 50 patients, and on reports from other laboratories that have measured the disturbances of eye movements. When these gaze disorders are approached by considering each functional class of eye movements and its neurobiological basis, a distinct pattern of eye movement deficits emerges that provides insight into the pathogenesis of PSP. Although some aspects of all forms of eye movements are affected in PSP, the predominant defects concern vertical saccades (slow and hypometric, both up and down), impaired vergence, and inability to modulate the linear vestibulo-ocular reflex appropriately for viewing distance. These vertical and vergence eye movements habitually work in concert to enable visuomotor skills that are important during locomotion with the hands free. Taken with the prominent early feature of falls, these findings suggest that PSP tauopathy impairs a recently evolved neural system concerned with bipedal locomotion in an erect posture and frequent gaze shifts between the distant environment and proximate hands. This approach provides a conceptual framework that can be used to address the nosological challenge posed by overlapping clinical and neuropathological features of neurodegenerative tauopathies.