The vergence-mediated gain increase: Physiology and clinical relevance.

BACKGROUND: During near-viewing, the vestibulo-ocular reflex (VOR) response/gain increases to compensate for the relatively larger translation of the eyes with respect to the target. OBJECTIVE: To review vergence-mediated gain increase (VMGI) testing methods stimuli and responses (latency and amplitude), peripheral/central pathways and clinical relevance. METHODS: The authors discuss publications listed in PUBMED since 1980 in the light of their own studies. RESULTS: The VMGI can be measured during rotational, linear and combined head accelerations. It has short-latency, non-compensatory amplitude, and relies on irregularly discharging peripheral afferents and their pathways. It is driven by a combination of perception, visual-context and internal modelling. CONCLUSIONS: Currently, there are technical barriers that hinder VMGI measurement in the clinic. However, the VMGI may have diagnostic value, especially with regards to measuring otolith function. The VMGI also may have potential value in rehabilitation by providing insight about a patient's lesion and how to best tailor a rehabilitation program for them, that potentially includes VOR adaptation training during near-viewing.

Unidirectional Vertical Vestibuloocular Reflex Adaptation in Humans Using 1D and 2D Scenes.

HYPOTHESIS: The vertical vestibuloocular reflex (VOR) in response to pitch head impulses can be optimally trained to increase in one direction using a two-dimensional (2D) visual training target with minimal effect on the horizontal VOR. BACKGROUND: We modified the incremental VOR adaptation (IVA) technique, shown to increase the horizontal VOR in patients with vestibular hypofunction, to drive vertical VOR adaptation in healthy control subjects. METHODS: We measured the horizontal and vertical active (self-generated) and passive (imposed) head impulse VOR gains (eye velocity/head velocity) before and after 15 minutes of unidirectional downward IVA training. IVA training consisted of two sessions, one using a single-dot one-dimensional (1D) target, the other a grid-of-dots 2D target. RESULTS: The downward head impulse VOR gain significantly increased because of training by 13.3%, whereas the upward VOR gain did not change. The addition of extraretinal (2D) feedback did not result in greater adaptation, i.e., 1D and 2D gain increases were 15.5% and 10.6%, respectively. The vertical VOR gain increase resulted in a 3.2% decrease in horizontal VOR gain. CONCLUSION: This preliminary study is the first to show that physiologically relevant (high frequency) unidirectional increases in vertical VOR gain are possible with just 15 minutes of training. This study sets the basis for future clinical trials examining vertical IVA training in patients, which may provide the first practical rehabilitation treatment to functionally improve the vertical VOR.

A Prospective Study on the Vestibular Toxicity of Gentamicin in a Clinical Setting.

OBJECTIVE: Gentamicin is a widely used aminoglycoside with ototoxicity as a known adverse effect. Because of the difficulty in clinical recognition, the prevalence of gentamicin ototoxicity in practice is thought to be higher than reported. This study aimed to prospectively assess the effect of gentamicin on vestibular function and whether ototoxicity is underrecognized. STUDY DESIGN: Single-center, prospective, nonblinded trial. SETTING: Inpatient tertiary hospital setting followed by vestibular outpatient clinic review. PATIENTS: Forty-eight patients undergoing a urologic procedure were recruited, with 24 and 17 patients having one or two follow-up tests, respectively, after initial gentamicin administration. INTERVENTIONS: Single dose of gentamicin during a urologic procedure. MAIN OUTCOME MEASURES: Gains for the vestibuloocular reflex (VOR) were measured using the video head impulse test before receiving gentamicin and at two other timepoints after gentamicin. The gains in VOR were then compared with previous testing sessions to determine if there was a deterioration after gentamicin use. RESULTS: Before receiving gentamicin, the gains for horizontal VOR were measured for 48 patients. The gains were measured a second time for 24 patients at varying durations postgentamicin (1-56 d) and a third time for 17 patients (14-152 d) postgentamicin. The mean VOR gain for Timepoints 1, 2, and 3 were 0.72 ± 0.13, 0.75 ± 0.16, and 0.79 ± 0.18, respectively. Linear-mixed model with repeated-measure analysis revealed no significant difference in VOR gain between Timepoints 1 and 2 ( p = 0.19). CONCLUSION: There was no significant effect observed on mean VOR gain decrement after a single dose of gentamicin.

Vestibulo-Ocular Reflex Short-Term Adaptation Is Halved After Compensation for Unilateral Labyrinthectomy.

Several prior studies, including those from this laboratory, have suggested that vestibulo-ocular reflex (VOR) adaptation and compensation are two neurologically related mechanisms. We therefore hypothesised that adaptation would be affected by compensation, depending on the amount of overlap between these two mechanisms. To better understand this overlap, we examined the effect of gain-increase (gain = eye velocity/head velocity) adaptation training on the VOR in compensated mice since both adaptation and compensation mechanisms are presumably driving the gain to increase. We tested 11 cba129 controls and 6 α9-knockout mice, which have a compromised efferent vestibular system (EVS) known to affect both adaptation and compensation mechanisms. Baseline VOR gains across frequencies (0.2 to 10 Hz) and velocities (20 to 100°/s) were measured on day 28 after unilateral labyrinthectomy (UL) and post-adaptation gains were measured after gain-increase training on day 31 post-UL. Our findings showed that after chronic compensation gain-increase adaptation, as a percentage of baseline, in both strains of mice (~14%), was about half compared to their previously reported healthy, non-operated counterparts (~32%). Surprisingly, there was no difference in gain-increase adaptation between control and α9-knockout mice. These data support the notion that adaptation and compensation are separate but overlapping processes. They also suggest that half of the original adaptation capacity remained in chronically compensated mice, regardless of EVS compromise associated with α9-knockout mice, and strongly suggest VOR adaptation training is a viable treatment strategy for vestibular rehabilitation therapy and, importantly, augments the compensatory process.

A Once-Daily High Dose of Intraperitoneal Ascorbate Improves Vestibulo-ocular Reflex Compensation After Unilateral Labyrinthectomy in the Mouse.

Ascorbate potentiates the response of nicotinic-acetylcholine-receptors containing α9 and α10 subunits found predominantly in the efferent systems of the inner ear, such as the efferent vestibular system (EVS). Prior mouse studies have shown that an attenuated EVS results in reduced vestibulo-ocular reflex (VOR) gain (=eye_velocity/head_velocity) plasticity in intact (VOR adaptation) and surgically-lesioned (VOR compensation) mice. We sought to determine whether ascorbate-treatment could improve VOR recovery after vestibular organ injury, possibly through potentiation of the EVS pathway. We tested 10 cba129 mice, 5 received ascorbate-treatment and 5 did not, but otherwise experienced the same conditions. Ascorbate-treatment comprised a once-daily intraperitoneal injection of L-form reduced ascorbate (4 g/kg) in 0.2 ml saline starting 1 week before, and ending 4 weeks after, unilateral labyrinthectomy surgery. These were deliberately high doses to determine the ascorbate effects on recovery. Baseline, acute, and chronic sinusoidal VOR gains (frequency and velocity ranges: 0.2-10 Hz, 20-100 deg/s) were measured 3-5 days before, 3-5 days after, and 28-31 days after labyrinthectomy. Mice treated with ascorbate had acute ipsilesional VOR gains 12 % higher compared to control mice (+45.2 ± 14.9 % from baseline versus +33.7 ± 15.4 %, P < 0.001). Similarly, chronic ipsilesional and contralesional VOR gains were respectively 16 % (+74.3 ± 16.3 % from baseline versus +58.1 ± 15.8 %, P < 0.001) and 13 % (+78.6 ± 16.0 % versus +65.6 ± 10.9 %, P < 0.001) higher compared to control mice. These data suggest ascorbate-treatment had a prophylactic effect reducing acute loss, and helped recovery during acute to chronic stages of compensation. One possible mechanism is that an ascorbate-enhanced EVS drives an increase in the number and sensitivity of irregular-discharging primary vestibular afferents, important for VOR plasticity.

Incremental Velocity Error as a New Treatment in Vestibular Rehabilitation (INVENT VPT) Trial: study protocol for a randomized controlled crossover trial.

BACKGROUND: A clinical pattern of damage to the auditory, visual, and vestibular sensorimotor systems, known as multi-sensory impairment, affects roughly 2% of the US population each year. Within the population of US military service members exposed to mild traumatic brain injury (mTBI), 15-44% will develop multi-sensory impairment following a mild traumatic brain injury. In the US civilian population, multi-sensory impairment-related symptoms are also a common sequela of damage to the vestibular system and affect ~ 300-500/100,000 population. Vestibular rehabilitation is recognized as a critical component of the management of multi-sensory impairment. Unfortunately, the current clinical practice guidelines for the delivery of vestibular rehabilitation are not evidence-based and primarily rely on expert opinion. The focus of this trial is gaze stability training, which represents the unique component of vestibular rehabilitation. The aim of the Incremental Velocity Error as a New Treatment in Vestibular Rehabilitation (INVENT VPT) trial is to assess the efficacy of a non-invasive, incremental vestibular adaptation training device for normalizing the response of the vestibulo-ocular reflex. METHODS: The INVENT VPT Trial is a multi-center randomized controlled crossover trial in which military service members with mTBI and civilian patients with vestibular hypofunction are randomized to begin traditional vestibular rehabilitation or incremental vestibular adaptation and then cross over to the alternate intervention after a prescribed washout period. Vestibulo-ocular reflex function and other functional outcomes are measured to identify the best means to improve the delivery of vestibular rehabilitation. We incorporate ecologically valid outcome measures that address the common symptoms experienced in those with vestibular pathology and multi-sensory impairment. DISCUSSION: The INVENT VPT Trial will directly impact the health care delivery of vestibular rehabilitation in patients suffering from multi-sensory impairment in three critical ways: (1) compare optimized traditional methods of vestibular rehabilitation to a novel device that is hypothesized to improve vestibulo-ocular reflex performance, (2) isolate the ideal dosing of vestibular rehabilitation considering patient burden and compliance rates, and (3) examine whether recovery of the vestibulo-ocular reflex can be predicted in participants with vestibular symptoms. TRIAL REGISTRATION: ClinicalTrials.gov NCT03846830 . Registered on 20 February 2019.

Comparison of Incremental Vestibulo-ocular Reflex Adaptation Training Versus x1 Training in Patients With Chronic Peripheral Vestibular Hypofunction: A Two-Year Randomized Controlled Trial.

BACKGROUND AND PURPOSE: A crossover, double-blinded randomized controlled trial to investigate once-daily incremental vestibulo-ocular reflex (VOR) adaptation (IVA) training over 2 years in people with stable and chronic peripheral vestibular hypofunction. METHODS: Twenty-one patients with peripheral vestibular hypofunction were randomly assigned to intervention-then-control (n = 12) or control-then-intervention (n = 9) groups. The task consisted of either x1 (control) or IVA training, once daily every day for 15 minutes over 6-months, followed by a 6-month washout, then repeated for arm 2 of the crossover. Primary outcome: vestibulo-ocular reflex gain. Secondary outcomes: compensatory saccades, dynamic visual acuity, static balance, gait, and subjective symptoms. Multiple imputation was used for missing data. Between-group differences were analyzed using a linear mixed model with repeated measures. RESULTS: On average patients trained once daily 4 days per week. IVA training resulted in significantly larger VOR gain increase (active: 20.6% ± 12.08%, P = 0.006; passive: 30.6% ± 25.45%, P = 0.016) compared with x1 training (active: -2.4% ± 12.88%, P = 0.99; passive: -0.6% ± 15.31%, P = 0.68) (P < 0.001). The increased IVA gain did not significantly reduce with approximately 27% persisting over the washout period. x1 training resulted in greater reduction of compensatory saccade latency (P = 0.04) and increase in amplitude (P = 0.02) compared with IVA training. There was no difference between groups in gait and balance measures; however, only the IVA group had improved total Dizziness Handicap Inventory (P = 0.006). DISCUSSION AND CONCLUSIONS: Our results suggest IVA improves VOR gain and reduces perception of disability more than conventional x1 training. We suggest at least 4 weeks of once-daily 4 days-per-week IVA training should be part of a comprehensive vestibular rehabilitation program.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A356).

Prevalence of Vestibular Disorders in Independent People Over 50 That Experience Dizziness.

People aged over 50 are the most likely to present to a physician for dizziness. It is important to identify the main cause of dizziness in order to develop the best treatment approach. Our goal was to determine the prevalence of benign paroxysmal positional vertigo (BPPV), and peripheral and central vestibular function in people that had experienced dizziness within the past year aged over 50. One hundred and ninety three community-dwelling participants aged 51-92 (68 ± 8.7 years; 117 females) were tested using the clinical and video head impulse test (cHIT and vHIT) to test high-frequency vestibular organ function; the head thrust dynamic visual acuity (htDVA) test to test high-frequency visual-stability; the dizziness handicap inventory (DHI) to measure the impact of dizziness; as well as sinusoidal and unidirectional rotational chair testing to test low- to mid-frequency peripheral and central vestibular function. From these assessments we computed the following measures: HIT gain; htDVA score; DHI score; sinusoidal (whole-body; 0.1-2 Hz with 30°/s peak-velocity) vestibulo-ocular reflex (VOR) gain and phase; transient (whole-body, 150°/s2 acceleration to 50°/s constant velocity) VOR gain and time constant; optokinetic nystagmus (OKN) gain and time constant (whole-body, 50°/s constant velocity rotation). Our study showed that BPPV, and peripheral or central vestibular hypofunction were present in 34% of participants, suggesting a vestibular cause to their dizziness. Over half (57%) of these with a likely vestibular cause had BPPV, which is more than twice the percentage reported in other dizzy clinic studies. Our findings suggest that the physical DHI score and VOR time constant were best at detecting those with non-BPPV vestibular loss, but should always be used in conjunction with cHIT or vHIT, and that the htDVA score and vHIT gain were best at detecting differences between ipsilesional and contralesional sides.

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 500 Hz stimuli.

Once-Daily Incremental Vestibular-Ocular Reflex Adaptation Training in Patients With Chronic Peripheral Vestibular Hypofunction: A 1-Week Randomized Controlled Study.

BACKGROUND AND PURPOSE: This was a double-blinded randomized controlled study to investigate the effects of once-daily incremental vestibulo-ocular reflex (VOR) training over 1 week in people with chronic peripheral vestibular hypofunction. METHODS: A total of 24 patients with peripheral vestibular hypofunction were randomly assigned to intervention (n = 13) or control (n = 11) groups. Training consisted of either x1 (control) or incremental VOR adaptation exercises, delivered once daily for 15 minutes over 4 days in 1 week. Primary outcome: VOR gain with video-oculography. Secondary outcomes: Compensatory saccades measured using scleral search coils, dynamic visual acuity, static balance, gait, and subjective symptoms. Between-group differences were analyzed with a linear mixed-model with repeated measures. RESULTS: There was a difference in the VOR gain increase between groups (P < 0.05). The incremental training group gain increased during active (13.4% ± 16.3%) and passive (12.1% ± 19.9%) head impulse testing (P < 0.02), whereas it did not for the control group (P = 0.59). The control group had reduced compensatory saccade latency (P < 0.02). Both groups had similarly improved dynamic visual acuity scores (P < 0.05). Both groups had improved dynamic gait index scores (P < 0.002); however, only the incremental group had improved scores for the 2 walks involving head oscillations at approximately 2 Hz (horizontal: P < 0.05; vertical: P < 0.02), increased gait speed (P < 0.02), and step length (P < 0.01) during normal gait, and improved total Dizziness Handicap Inventory (P < 0.05). CONCLUSIONS: Our results suggest incremental VOR adaptation significantly improves gain, gait with head rotation, balance during gait, and symptoms in patients with chronic peripheral vestibular hypofunction more so than conventional x1 gaze-stabilizing exercises.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A336).

Absence of a vergence-mediated vestibulo-ocular reflex gain increase does not preclude adaptation.

BACKGROUND: The gain (eye-velocity/head-velocity) of the angular vestibuloocular reflex (aVOR) during head impulses can be increased while viewing near-targets and when exposed to unilateral, incremental retinal image velocity error signals. It is not clear however, whether the tonic or phasic vestibular pathways mediate these gain increases. OBJECTIVE: Determine whether a shared pathway is responsible for gain enhancement between vergence and adaptation of aVOR gain in patients with unilateral vestibular hypofunction (UVH). MATERIAL AND METHODS: 20 patients with UVH were examined for change in aVOR gain during a vergence task and after 15-minutes of ipsilesional incremental VOR adaptation (uIVA) using StableEyes (a device that controls a laser target as a function of head velocity) during horizontal passive head impulses. A 5 % aVOR gain increase was defined as the threshold for significant change. RESULTS: 11/20 patients had >5% vergence-mediated gain increase during ipsi-lesional impulses. For uIVA, 10/20 patients had >5% ipsi-lesional gain increase. There was no correlation between the vergence-mediated gain increase and gain increase after uIVA training. CONCLUSION: Vergence-enhanced and uIVA training gain increases are mediated by separate mechanisms and/or vestibular pathways (tonic/phasic). The ability to increase the aVOR gain during vergence is not prognostic for successful adaptation training.

Human Vestibulo-Ocular Reflex Adaptation Reduces when Training Demand Variability Increases.

One component of vestibular rehabilitation in patients with vestibulo-ocular reflex (VOR) hypofunction is gaze-stabilizing exercises that seek to increase (adapt) the VOR response. These prescribed home-based exercises are performed by the patient and thus their use/training is inherently variable. We sought to determine whether this variability affected VOR adaptation in ten healthy controls (× 2 training only) and ten patients with unilateral vestibular hypofunction (× 1 and × 2 training). During × 1 training, patients actively (self-generated, predictable) move their head sinusoidally while viewing a stationary fixation target; for × 2 training, they moved their outstretched hand anti-phase with their head rotation while attempting to view a handheld target. We defined the latter as manual × 2 training because the subject manually controls the target. In this study, head rotation frequency during training incrementally increased 0.5-2 Hz over 20 min. Active and passive (imposed, unpredictable) sinusoidal (1.3-Hz rotations) and head impulse VOR gains were measured before and after training. We show that for controls, manual × 2 training resulted in significant sinusoidal and impulse VOR adaptation of ~ 6 % and ~ 3 %, respectively, though this was ~two-thirds lower than increases after computer-controlled × 2 training (non-variable) reported in a prior study. In contrast, for patients, there was an increase in impulse but not sinusoidal VOR response after a single session of manual × 2 training. Patients had more than double the variability in VOR demand during manual × 2 training compared to controls, which could explain why adaptation was not significant in patients. Our data suggest that the clinical × 1 gaze-stabilizing exercise is a weak stimulus for VOR adaptation.

The instantaneous training demand drives vestibulo-ocular reflex adaptation.

The vestibulo-ocular reflex (VOR) maintains stable vision during rapid head rotations by rotating the eyes in the opposite direction to the head. The latency between onset of the head rotation and onset of the eye rotation is 5-8 ms in healthy humans. However, VOR latency can be 3-4 times larger in patients treated with intra-tympanic gentamicin. A prior study showed that latency can be trained with head rotations at 0.2 Hz. We sought to determine how the VOR is affected when a delay between vestibular and visual stimuli is added during adaptation training with high-frequency head rotations (impulses), where the VOR is the main vision-stabilizing system. Using a variant of the incremental VOR adaptation technique, the delay between head rotation onset and movement onset of a visual target was gradually increased. With this training, the instantaneous VOR gain demand (= target/head velocity) varied from less than unity to greater than unity during each head impulse, albeit in a consistent and repeatable way. We measured the active and passive VOR gain and latency before and after VOR adaptation training in healthy normal subjects. There was no significant change in VOR latency across subjects; however, there was a significant decrease in VOR gain of - 6.0 ± 4.5%. These data suggest that during high-frequency head rotations delay/latency is interpreted as a changing instantaneous VOR gain demand. Although the gain demand in this study had a complex trajectory, adaptation was evident with the VOR seeming to use an average of the instantaneous gain demand.

Retinal Image Slip Must Pass the Threshold for Human Vestibulo-Ocular Reflex Adaptation.

We sought to determine whether repeated vestibulo-ocular reflex (VOR) adaptation training to increase the VOR gain (eye/head velocity) had a lasting effect in normal subjects and whether there was a retinal image slip tolerance threshold for VOR adaptation. We used the unilateral incremental VOR adaptation technique and horizontal active (self-generated, predictable) head impulses as the vestibular stimulus. Both active and passive (imposed, unpredictable) head impulse VOR gains were measured before and after unilateral incremental VOR adaptation training. The adapting side was pseudo-randomized for left or right. We tested ten normal subjects over one block (10 sessions over 12 days) of VOR adaptation training and testing, immediately followed by a second block (5 sessions over 19 days) of testing only without training. Our findings show robust short-term VOR adaptation of ~ 10 % immediately after each 15-min training session, but that the daily pre-adaptation gain was most different on days 1 and 2, and for subsequent training days before saturating to ~ 5 % greater than the pre-adaptation gain on day 1. This increase was partially retained for 19 days after regular training stopped. The data suggest that stable vision in normal subjects is maintained when there is < 5 % deviation in VOR gain from the original baseline, which corresponds to < 9°/s retinal image slip. Below this threshold, there is poor adaptive drive to return the gain to its original baseline value.

Identifying Key Risk Factors for Dizziness Handicap in Middle-Aged and Older People.

OBJECTIVES: More than 10% of people aged 50 years and older report dizziness. Despite available treatments, dizziness remains unresolved for many people due in part to suboptimal assessment. We aimed to identify factors associated with dizziness handicap in middle-aged and older people to identify targets for intervention to address this debilitating problem. A secondary aim was to determine whether factors associated with dizziness differed between middle-aged (<70 years) and older people (≥ 70 years). DESIGN: Secondary analysis of baseline and prospective data from a randomized controlled trial. SETTING AND PARTICIPANTS: In total, 305 individuals aged 50 to 92 years reporting significant dizziness in the past year were recruited from the community. METHODS: Participants were classified as having either mild or no dizziness handicap (score <31) or moderate/severe dizziness handicap (score: 31‒100) based on the Dizziness Handicap Inventory. Participants completed health questionnaires and underwent assessments of psychological well-being, lying and standing blood pressure, vestibular function, strength, vision, proprioception, processing speed, balance, stepping, and gait. Participants reported dizziness episodes in monthly diaries for 6 months following baseline assessment. RESULTS: Dizziness Handicap Inventory scores ranged from 0 to 86 with 95 participants (31%) reporting moderate/severe dizziness handicap. Many vestibular, cardiovascular, psychological, balance-related, and medical/medications measures were significantly associated with dizziness handicap severity and dizziness episode frequency. Binary logistic regression identified a positive Dix Hallpike/head-roll test for benign paroxysmal positional vertigo [odds ratio (OR) 2.09, 95% confidence interval (CI) (1.11‒3.97)], cardiovascular medication use [OR 1.90, 95% CI (1.09‒3.32)], high postural sway when standing on the floor with eyes closed (sway path ≥160 mm) [OR 2.97, 95% CI (1.73‒5.10)], and anxiety (Generalized Anxiety Disorder Scale 7-item Scale score ≥8) [OR 3.08, 95% CI (1.36‒6.94)], as significant and independent predictors of moderate/severe dizziness handicap. Participants aged 70 years and over were significantly more likely to report cardiovascular conditions than those aged less than 70 years old. CONCLUSIONS AND IMPLICATIONS: Assessments of cardiovascular conditions and cardiovascular medication use, benign paroxysmal positional vertigo, anxiety, and postural sway identify middle-aged and older people with significant dizziness handicap. A multifactorial assessment including these factors may assist in tailoring evidence-based therapies to alleviate dizziness handicap in this group.

Horizontal Vestibulo-Ocular Reflex Gain Measures During Convergence Using a Monocular Video Technique.

HYPOTHESIS: Vestibulo-ocular reflex (VOR) response measures during convergence, which are clinically important to measure peripheral vestibular organ function during rotational and translational rapid head movements, can be implemented using existing clinically available monocular video-oculography (VOG) systems. BACKGROUND: We have developed and validated a monocular VOG technique that allows for accurate measurement of the convergence angle immediately before a rapid translational or rotational head movement. METHODS: We recorded binocular eye movements while subjects performed active or passive horizontal head impulses while viewing near and far targets. We calculated the convergence angles and VOR gains using monocular and binocular methods and compared them with a geometric model. RESULTS: The monocular VOG technique resulted in convergence angle and VOR gain (eye velocity/head velocity) calculations that differed by ∼10% compared with values calculated using the binocular data. CONCLUSIONS: The monocular VOG technique can be clinically implemented using any unmodified, commercially available, monocular VOG system, provided its camera can be positioned to track either eye. Many vestibular clinics already have access to such systems. This method makes possible reliable measurement of the near-viewing horizontal angular VOR during the head impulse test, the translational VOR during the head heave test in patients, and the clinical measurement of convergence insufficiency.

Human vestibulo-ocular reflex adaptation is frequency selective.

The vestibulo-ocular reflex (VOR) is the only system that maintains stable vision during rapid head rotations. The VOR gain (eye/head velocity) can be trained to increase using a vestibular-visual mismatch stimulus. We sought to determine whether low-frequency (sinusoidal) head rotation during training leads to changes in the VOR during high-frequency head rotation testing, where the VOR is more physiologically relevant. We tested eight normal subjects over three sessions. For training protocol 1, subjects performed active sinusoidal head rotations at 1.3 Hz while tracking a laser target, whose velocity incrementally increased relative to head velocity so that the VOR gain required to stabilize the target went from 1.1 to 2 over 15 min. Protocol 2 was the same as protocol 1, except that head rotations were at 0.5 Hz. For protocol 3, head rotation frequency incrementally increased from 0.5 to 2 Hz over 15 min, while the VOR gain required to stabilize the target was kept at 2. We measured the active and passive, sinusoidal (1.3Hz) and head impulse VOR gains before and after each protocol. Sinusoidal and head impulse VOR gains increased in protocols 1 and 3; however, although the sinusoidal VOR gain increase was ~20%, the related head impulse gain increase was only ~10%. Protocol 2 resulted in no-gain adaptation. These data show human VOR adaptation is frequency selective, suggesting that if one seeks to increase the higher-frequency VOR response, i.e., where it is physiologically most relevant, then higher-frequency head movements are required during training, e.g., head impulses.NEW & NOTEWORTHY This study shows that human vestibulo-ocular reflex adaptation is frequency selective at frequencies >0.3 Hz. The VOR in response to mid- (1.3 Hz) and high-frequency (impulse) head rotations were measured before and after mid-frequency sinusoidal VOR adaptation training, revealing that the mid-frequency gain change was higher than high-frequency gain change. Thus, if one seeks to increase the higher-frequency VOR response, where it is physiologically most relevant, then higher-frequency head movements are required during training.

New advances regarding adaptation of the vestibulo-ocular reflex.

This is a review summarizing the development of vestibulo-ocular reflex (VOR) adaptation behavior with relevance to rehabilitation over the last 10 years and examines VOR adaptation using head-on-body rotations, specifically the influence of training target contrast, position and velocity error signal, active vs. passive head rotations, and sinusoidal vs. head impulse rotations. This review discusses optimization of the single VOR adaptation training session, consolidation between repeated training sessions, and dynamic incremental VOR adaptation. Also considered are the effects of aging and the roles of the efferent vestibular system, cerebellum, and otoliths on angular VOR adaptation. Finally, this review examines VOR adaptation findings in studies using whole body rotations.

Improved Oculomotor Physiology and Behavior After Unilateral Incremental Adaptation Training in a Person With Chronic Vestibular Hypofunction: A Case Report.

BACKGROUND AND PURPOSE: Traditional vestibular rehabilitation therapies are effective in reducing vestibular hypofunction symptoms, but changes to the vestibulo-ocular reflex (VOR) are minimal. This controlled case report describes an increase in VOR after 6 months of incremental VOR adaptation (IVA) training in a person with chronic unilateral vestibular hypofunction. CASE DESCRIPTION: The participant was a 58-year-old female with a confirmed (Neurologist P.D.C.) left vestibular lesion stable for 2 years prior to entering a clinical trial examining the effects of daily IVA training. She was evaluated monthly for self-reported symptoms (dizziness handicap inventory), VOR function (video head impulse test), and VOR behavior (Dynamic Visual Acuity test). Intervention consisted of 6 months of 15 minutes per day unassisted training using the IVA training regime with a device developed in our laboratory. The take-home device enables the VOR response to gradually normalize on the ipsilesional side via visual-vestibular mismatch training. The intervention was followed by a 6-month wash-out and 3-month control period. The control condition used the same training device set to function like standard VOR training indistinguishable to the participant. OUTCOMES: After the intervention, ipsilesional VOR function improved substantially. The VOR adapted both via a 52% increase in slow-phase response and via 43% earlier onset compensatory saccades for passive head movements. In addition, the participant reported fewer symptoms and increased participation in sports and daily activities. DISCUSSION: Here, a participant with chronic vestibular hypofunction showing improved oculomotor performance atypical for traditional vestibular rehabilitation therapies, subsequent to using the newly developed IVA technique, is presented. It is the first time to our knowledge an improvement of this magnitude has been demonstrated as well as sustained over an extended period of time.

Angular vestibuloocular reflex responses in Otop1 mice. II. Otolith sensor input improves compensation after unilateral labyrinthectomy.

The role of the otoliths in mammals in the normal angular vestibuloocular reflex (VOR) was characterized in an accompanying study based on the Otopetrin1 (Otop1) mouse, which lacks functioning otoliths because of failure to develop otoconia but seems to have otherwise normal peripheral anatomy and neural circuitry. That study showed that otoliths do not contribute to the normal horizontal (rotation about Earth-vertical axis parallel to dorso-ventral axis) and vertical (rotation about Earth-vertical axis parallel to interaural axis) angular VOR but do affect gravity context-specific VOR adaptation. By using these animals, we sought to determine whether the otoliths play a role in the angular VOR after unilateral labyrinthectomy when the total canal signal is reduced. In five Otop1 mice and five control littermates we measured horizontal and vertical left-ear-down and right-ear-down sinusoidal VOR (0.2-10 Hz, 20-100°/s) during the early (3-5 days) and plateau (28-32 days) phases of compensation after unilateral labyrinthectomy and compared these measurements with baseline preoperative responses from the accompanying study. From similar baselines, acute gain loss was ~25% less in control mice, and chronic gain recovery was ~40% more in control mice. The acute data suggest that the otoliths contribute to the angular VOR when there is a loss of canal function. The chronic data suggest that a unilateral otolith signal can significantly improve angular VOR compensation. These data have implications for vestibular rehabilitation of patients with both canal and otolith loss and the development of vestibular implants, which currently only mimic the canals on one side. NEW & NOTEWORTHY This is the first study examining the role of the otoliths (defined here as the utricle and saccule) on the acute and chronic angular vestibuloocular reflex (VOR) after unilateral labyrinthectomy in an animal model in which the otoliths are reliably inactivated and the semicircular canals preserved. This study shows that the otolith signal is used to augment the acute angular VOR and help boost VOR compensation after peripheral injury.