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 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. I. Otolith sensor input is essential for gravity context-specific adaptation

The role of the otoliths in mammals in the angular vestibuloocular reflex (VOR) has been difficult to determine because there is no surgical technique that can reliably ablate them without damaging the semicircular canals. The Otopetrin1 (Otop1) mouse lacks functioning otoliths because of failure to develop otoconia but seems to have otherwise normal peripheral anatomy and neural circuitry. By using these animals we sought to determine the role of the otoliths in angular VOR baseline function and adaptation. In six Otop1 mice and six control littermates we measured baseline ocular countertilt about the three primary axes in head coordinates; baseline horizontal (rotation about an Earth-vertical axis parallel to the dorsal-ventral axis) and vertical (rotation about an Earth-vertical axis parallel to the interaural axis) sinusoidal (0.2–10 Hz, 20–100°/s) VOR gain (= eye/head velocity); and the horizontal and vertical VOR after gain-increase (1.5×) and gain-decrease (0.5×) adaptation training. Countertilt responses were significantly reduced in Otop1 mice. Baseline horizontal and vertical VOR gains were similar between mouse types, and so was horizontal VOR adaptation. For control mice, vertical VOR adaptation was evident when the testing context, left ear down (LED) or right ear down (RED), was the same as the training context (LED or RED). For Otop1 mice, VOR adaptation was evident regardless of context. Our results suggest that the otolith translational signal does not contribute to the baseline angular VOR, probably because the mouse VOR is highly compensatory, and does not alter the magnitude of adaptation. However, we show that the otoliths are important for gravity context-specific angular VOR adaptation. NEW & NOTEWORTHY This is the first study examining the role of the otoliths (defined here as the utricle and saccule) in adaptation of the angular vestibuloocular reflex (VOR) in an animal model in which the otoliths are reliably inactivated and the semicircular canals preserved. We show that they do not contribute to adaptation of the normal angular VOR. However, the otoliths provide the main cue for gravity context-specific VOR adaptation.

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.

A neuroanatomically grounded optimal control model of the compensatory eye movement system

We present a working model of the compensatory eye movement system. We challenge the model with a data set of eye movements in mice (n=34) recorded in 4 different sinusoidal stimulus conditions with 36 different combinations of frequency (0.1-3.2 Hz) and amplitude (0.5-8°) in each condition. The conditions included vestibular stimulation in the dark (vestibular-ocular reflex, VOR), optokinetic stimulation (optokinetic reflex, OKR), and two combined visual/vestibular conditions (the visual-vestibular ocular reflex, vVOR, and visual suppression of the VOR, sVOR). The model successfully reproduced the eye movements in all conditions, except for minor failures to predict phase when gain was very low. Most importantly, it could explain the non-linear summation of VOR and OKR when the two reflexes are activated simultaneously during vVOR stimulation. In addition to our own data, we also reproduced the behavior of the compensatory eye movement system found in the existing literature. These include its response to sum-of-sines stimuli, its response after lesions of the nucleus prepositus hypoglossi or the flocculus, characteristics of VOR adaptation, and characteristics of drift in the dark. Our model is based on ideas of state prediction and forward modeling that have been widely used in the study of motor control. However, it represents one of the first quantitative efforts to simulate the full range of behaviors of a specific system. The model has two separate processing loops, one for vestibular stimulation and one for visual stimulation. Importantly, state prediction in the visual processing loop depends on a forward model of residual retinal slip after vestibular processing. In addition, we hypothesize that adaptation in the system is primarily adaptation of this model. In other words, VOR adaptation happens primarily in the OKR loop.

Simultaneous and opposing horizontal VOR adaptation in humans suggests functionally independent neural circuits

The healthy vestibulo-ocular reflex (VOR) ensures that images remain on the fovea of the retina during head rotation to maintain stable vision. VOR behavior can be measured as a summation of linear and nonlinear properties although it is unknown whether asymmetric VOR adaptation can be performed synchronously in humans. The purpose of the present study is twofold. First, examine whether the right and left VOR gains can be synchronously adapted in opposing directions. Second, to investigate whether the adaptation context transfers between both sides. Three separate VOR adaptation sessions were randomized such that the VOR was adapted Up-bilaterally, Down-bilaterally, or Mixed (one side up, opposite side down). Ten healthy subjects completed the study. Subjects were tested while seated upright, 1 meter in front of a wall in complete dark. Each subject made active (self-generated) head impulse rotations for 15 min while viewing a gradually increasing amount of retinal slip. VOR training demand changed by 10% every 90 s. The VOR changed significantly for all training conditions. No significant differences in the magnitude of VOR gain changes between training conditions were found. The human VOR can be simultaneously driven in opposite directions. The similar magnitude of VOR gain changes across training conditions suggests functionally independent VOR circuits for each side of head rotation that mediate simultaneous and opposing VOR adaptations. NEW & NOTEWORTHY Our results indicate that humans have the adaptive capacity for concurrent and opposing directions of vestibulo-ocular reflex (VOR) motor learning. Context specificity of VOR adaptation is dependent on the error signal being unilateral or bilateral, which we illustrate via a lack of VOR gain transfer using unique adaptive demands.