Vestibulo-ocular Reflex Performance Research Articles

Multisensory gaze stabilization in response to subchronic alteration of vestibular type I hair cells

The functional complementarity of the vestibulo-ocular reflex (VOR) and optokinetic reflex (OKR) allows for optimal combined gaze stabilization responses (CGR) in light. While sensory substitution has been reported following complete vestibular loss, the capacity of the central vestibular system to compensate for partial peripheral vestibular loss remains to be determined. Here, we first demonstrate the efficacy of a 6-week subchronic ototoxic protocol in inducing transient and partial vestibular loss which equally affects the canal- and otolith-dependent VORs. Immunostaining of hair cells in the vestibular sensory epithelia revealed that organ-specific alteration of type I, but not type II, hair cells correlates with functional impairments. The decrease in VOR performance is paralleled with an increase in the gain of the OKR occurring in a specific range of frequencies where VOR normally dominates gaze stabilization, compatible with a sensory substitution process. Comparison of unimodal OKR or VOR versus bimodal CGR revealed that visuo-vestibular interactions remain reduced despite a significant recovery in the VOR. Modeling and sweep-based analysis revealed that the differential capacity to optimally combine OKR and VOR correlates with the reproducibility of the VOR responses. Overall, these results shed light on the multisensory reweighting occurring in pathologies with fluctuating peripheral vestibular malfunction.

Multisensory gaze stabilization in response to subchronic alteration of vestibular type I hair cells.

The functional complementarity of the vestibulo-ocular reflex (VOR) and optokinetic reflex (OKR) allows for optimal combined gaze stabilization responses (CGR) in light. While sensory substitution has been reported following complete vestibular loss, the capacity of the central vestibular system to compensate for partial peripheral vestibular loss remains to be determined. Here, we first demonstrate the efficacy of a 6-week subchronic ototoxic protocol in inducing transient and partial vestibular loss which equally affects the canal- and otolith-dependent VORs. Immunostaining of hair cells in the vestibular sensory epithelia revealed that organ-specific alteration of type I, but not type II, hair cells correlates with functional impairments. The decrease in VOR performance is paralleled with an increase in the gain of the OKR occurring in a specific range of frequencies where VOR normally dominates gaze stabilization, compatible with a sensory substitution process. Comparison of unimodal OKR or VOR versus bimodal CGR revealed that visuo-vestibular interactions remain reduced despite a significant recovery in the VOR. Modeling and sweep-based analysis revealed that the differential capacity to optimally combine OKR and VOR correlates with the reproducibility of the VOR responses. Overall, these results shed light on the multisensory reweighting occurring in pathologies with fluctuating peripheral vestibular malfunction.

Astronauts eye-head coordination dysfunction over the course of twenty space shuttle flights.

Coordination of motor activity is adapted to Earth's gravity (1 g). However, during space flight the gravity level changes from Earth gravity to hypergravity during launch, and to microgravity (0 g) in orbit. This transition between gravity levels may alter the coordination between eye and head movements in gaze performance. We explored how weightlessness during space flight altered the astronauts' eye-head coordination (EHC) with respect to flight day and target eccentricity. Thirty-four astronauts of 20 Space Shuttle missions had to acquire visual targets with angular offsets of 20°, 30°, and 49°. Measurements of eye, head, and gaze positions collected before and during flight days 1 to 15 indicated changes during target acquisition that varied as a function of flight days and target eccentricity. The in-flight alterations in EHC were presumably the result of a combination of several factors, including a transfer from allocentric to egocentric reference for spatial orientation in absence of a gravitational reference, the generation of slower head movements to attenuate motion sickness, and a decrease in smooth pursuit and vestibulo-ocular reflex performance. These results confirm that humans have several strategies for gaze behavior, between which they switch depending on the environmental conditions.

Clinical value of vestibulo-ocular reflex in the differentiation of spinocerebellar ataxias

The diagnosis of spinocerebellar ataxia (SCA) currently depends upon genetic testing. Although genetic testing for SCA is highly specific, clinical parameters for the differentiation of SCAs are still insufficient. We aimed to assess the vestibulo-ocular reflex (VOR) parameters of various SCA subtypes to determine whether they have substantial value in differential diagnosis. We consecutively enrolled 33 genetically confirmed SCA patients (SCA2 = 8, SCA3 = 6, SCA6 = 10, SCA7 = 9). Normative data were obtained from 36 age- and gender-matched healthy controls. Quantitative indicators of VOR were measured using video head impulse test (HIT) and combined ocular motor dysfunctions were investigated using video-oculography. Compared with the control group, the VOR gains in SCA2 were relatively spared, but were markedly decreased for all six canals in SCA3. The VOR gains for the posterior canals (PCs) were significantly decreased in SCA6, and for both vertical canals were decreased in SCA7. The VOR gains for the horizontal canals in SCA3 were negatively correlated with disease severity (R = -0.900, p = 0.037). Abnormal catch-up saccades were common in SCA3 and SCA6, rare in SCA7 and absent in SCA2. Spontaneous, headshaking-induced, and positional nystagmus were only documented in SCA6. SCA3 and SCA6 commonly showed horizontal gaze-evoked nystagmus, but SCA2 and SCA7 had characteristic saccadic slowing without gaze-evoked nystagmus. VOR impairments are common in SCAs, but their patterns vary depending on subtype. In addition to ocular motor characteristics, distinctive VOR performance for each subtype using video HIT may aid the differential diagnosis of the SCA genotypes.

Expression of a Form of Cerebellar Motor Memory Requires Learned Alterations to the Activity of Inhibitory Molecular Layer Interneurons.

Procedural memories formed in the cerebellum in response to motor errors depend on changes to Purkinje cell (PC) spiking patterns that correct movement when the erroneous context is repeated. Because molecular layer interneurons (MLIs) inhibit PCs, learning-induced changes to MLI output may participate in reshaping PC spiking patterns. However, it remains unclear whether error-driven learning alters MLI activity and whether such changes are necessary for the memory engram. We addressed this knowledge gap by measuring and manipulating MLI activity in the flocculus of both sexes of mice before and after vestibulo-ocular reflex (VOR) adaptation. We found that MLIs are activated during vestibular stimuli and that their population response exhibits a phase shift after the instantiation of gain-increase VOR adaptation, a type of error-driven learning thought to require climbing-fiber-mediated instructive signaling. Although acute optogenetic suppression of MLI activity did not affect baseline VOR performance, it negated the expression of gain-increase learning, demonstrating a specific role of MLI activity changes in motor memory expression. This effect was transitory; after a multiday consolidation period, the expression of VOR gain-increase learning was no longer sensitive to MLI activity suppression. Together, our results indicate that error-driven alteration of MLI activity is necessary for labile, climbing-fiber-induced motor memory expression.SIGNIFICANCE STATEMENT In the cerebellum, motor learning induces an associative memory of the sensorimotor context of an erroneous movement that, when recalled, results in a new pattern of output that improves subsequent trials of performance. Our study shows that error-driven motor learning induces changes to the activity pattern of cerebellar molecular layer interneurons (MLIs) and that this new pattern of activity is required to express the corrective motor memory.

Determining the Agreement Between Common Measures Related to Vestibulo-ocular Reflex Function After a Mild Traumatic Brain Injury in Children and Adolescents

ObjectiveTo (1) determine the level of agreement between symptom provocation and performance-based tests of vestibulo-ocular reflex (VOR) function after pediatric mild traumatic brain injury (mTBI) and (2) describe the level of symptom provocation induced by a VOR task in individuals with and without cervical findings. DesignCross-sectional. SettingThis study was conducted at a tertiary care pediatric hospital. ParticipantsA total of 101 participants (N=101) aged 6-18 years within 3 weeks of mTBI diagnosis were included (54.5% female; mean age, 13.92±2.63 years; mean time since injury at assessment, 18.26±6.16 days). InterventionsNone. Main Outcome MeasuresSymptom provocation (Vestibular/Ocular Motor Screening tool), performance (clinician-observed VOR performance, head thrust test [HTT], computerized dynamic visual acuity test, video head impulse test), and cervical impairment (cervical flexion-rotation test, range of motion test, self-reported neck pain). Agreement was evaluated using Cohen's κ statistic. ResultsNo outcomes demonstrated agreement with symptom provocation (κ=−0.15 to 0.14). Fair agreement demonstrated between clinician-observed VOR performance and HTT (κ=0.32), with little to no agreement demonstrated between other measures. Proportions reporting test-induced dizziness and headache were greater among individuals with cervical findings (29.1%-41.8%) than without (2.3%-6.8%). ConclusionsFindings support that symptom provocation and performance-based tests measure different constructs and thus have distinct roles when assessing VOR function. Findings suggest results from measures of symptom provocation may be influenced by coexisting cervical impairments, underlining the value of assessing for cervical injury after pediatric mTBI.

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

BackgroundA 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.MethodsThe 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.DiscussionThe 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 registrationClinicalTrials.gov NCT03846830. Registered on 20 February 2019.

Determining the Agreement Between Common Measures Of VOR Function After A Mild Traumatic Brain Injury in Children and Adolescents

<h3>Research Objectives</h3> Alterations to vestibulo-ocular reflex (VOR) function (1-3) and cervical spine injury (4-6) may contribute to dizziness reported following pediatric mild traumatic brain injury (mTBI). Moreover, dizziness has been correlated with a more negative prognosis. While various measures are used to assess VOR function, there is no consensus on what the optimal battery of tests may be. The influence of cervical injury on findings from these tests remains unclear. Objectives: i) to determine the level of agreement between symptom- and performance-based tests of VOR function in a pediatric mTBI sample; ii) to characterize the level of symptom provocation induced by VOR tests in individuals with and without cervical findings. <h3>Design</h3> Cross-sectional study. <h3>Setting</h3> Tertiary care pediatric hospital. <h3>Participants</h3> 101 participants (54.5% female), mean age 13.92 years (SD 2.63), completed a VOR assessment (mean time since injury 18.26 days (SD 6.16)). <h3>Interventions</h3> N/A. <h3>Main Outcome Measures</h3> Symptom provocation was measured by the Vestibular/ocular motor screening tool (VOMS). Performance was measured by VOMS VOR performance, the head thrust test (HTT), the computerized dynamic visual acuity test, and the video head impulse test. Cervical impairment was measured by the cervical flexion rotation test, range of motion test and self-reported neck pain. <h3>Results</h3> No outcomes demonstrated agreement with VOR symptom provocation (k=-0.15-0.14). Among performance-based measures, fair agreement was demonstrated between VOMS VOR performance and the clinical HTT (k=0.32), while little to no agreement was demonstrated between the remaining measures. VOR dizziness symptoms were reported in a greater proportion of individuals with cervical findings (41.1-41.8%) than without (2.3-6.8%). <h3>Conclusions</h3> The findings indicate i) that symptom-based VOR tests measure a different construct than performance-based tests, ii) the distinct role of each measure when assessing VOR function should be further understood, and iii) cervical injury may contribute to symptoms induced by tests of VOR function. <h3>Author(s) Disclosures</h3> The authors have no conflicts of interest to disclose. This study was funded by an ERA-Net NEURON JTC Cofund Program.

Compromised Survival of Cerebellar Molecular Layer Interneurons Lacking GDNF Receptors GFRα1 or RET Impairs Normal Cerebellar Motor Learning

SummaryThe role of neurotrophic factors as endogenous survival proteins for brain neurons remains contentious. In the cerebellum, the signals controlling survival of molecular layer interneurons (MLIs) are unknown, and direct evidence for the requirement of a full complement of MLIs for normal cerebellar function and motor learning has been lacking. Here, we show that Purkinje cells (PCs), the target of MLIs, express the neurotrophic factor GDNF during MLI development and survival of MLIs depends on GDNF receptors GFRα1 and RET. Conditional mutant mice lacking either receptor lose a quarter of their MLIs, resulting in compromised synaptic inhibition of PCs, increased PC firing frequency, and abnormal acquisition of eyeblink conditioning and vestibulo-ocular reflex performance, but not overall motor activity or coordination. These results identify an endogenous survival mechanism for MLIs and reveal the unexpected vulnerability and selective requirement of MLIs in the control of cerebellar-dependent motor learning.

Assessment of vestibulo-ocular function without measuring eye movements

BackgroundThe vestibulo-ocular reflex (VOR) maintains stable gaze during head motion. Deficiencies lead to apparent world motion due to incomplete stabilization of eyes in space. VOR measurement requires specialized apparatus, trained operators, and significant setup time. New methodWe present a system (VON: vestibulo-ocular nulling) for rapid vestibulo-ocular assessment without measuring eye movements per se. VON uses a head-mounted motion sensor, laptop computer with user input control, and laser target whose position is controlled by the computer. As the head moves, the target is made to move in the same manner with a gain set by the subject. When the subject sets the gain so the target appears stationary in space, it is stationary on the retinas. One can determine from this gain the extent to which the eyes move in space when the head moves, which is the amount by which the VOR is deficient. From this the gain of the compensatory eye movements is derived. ResultsVON was compared with conventional video-based VOR measures. Both methods track expected changes in gain over 20min of adaptation to minifying spectacles. VON measures are more consistent across subjects, and pre-adaptation values are closer to compensatory. Comparison with existing methodVON is a rapid means to assess vestibulo-ocular performance. As a functional perceptual measure, it accounts for gaze-stabilizing contributions that are not apparent in the standard VOR, such as pursuit and perceptual tolerance. ConclusionsVON assesses functional VOR performance. Future implementations will make VOR assessment widely available to investigators and clinicians.

Intra-Attack Vestibuloocular Reflex Changes in Ménière's Disease.

Ménière's attack has been shown to temporarily alter the vestibuloocular reflex (VOR). A patient with unilateral Ménière's disease was serially evaluated with the video Head Impulse Test during single, untreated episodes of acute vertigo. Spontaneous nystagmus activity was concurrently recorded in order to establish the three typical phases of Ménière's attack (irritative, paralytic, and recovery) and correlate them with VOR performance. The onset of attack was associated with a quick change in VOR gain on the side of the affected ear. While a rapidly progressive reduction of the VOR was evident at the paralytic nystagmus phase, in the recovery phase the VOR gain returned to normal and the direction of the previous nystagmus reversed. The membrane rupture potassium intoxication theory provides a good foundation with which to explain these dynamic VOR changes and the observed triphasic direction behavior of the spontaneous nystagmus. We additionally postulated that endolymphatic fluid displacement could have a synergic effect during the earliest phase of attack.

The Video Head Impulse Test (vHIT) of Semicircular Canal Function - Age-Dependent Normative Values of VOR Gain in Healthy Subjects.

The video Head Impulse Test (vHIT) is now widely used to test the function of each of the six semicircular canals individually by measuring the eye rotation response to an abrupt head rotation in the plane of the canal. The main measure of canal adequacy is the ratio of the eye movement response to the head movement stimulus, i.e., the gain of the vestibulo-ocular reflex (VOR). However, there is a need for normative data about how VOR gain is affected by age and also by head velocity, to allow the response of any particular patient to be compared to the responses of healthy subjects in their age range. In this study, we determined for all six semicircular canals, normative values of VOR gain, for each canal across a range of head velocities, for healthy subjects in each decade of life. The VOR gain was measured for all canals across a range of head velocities for at least 10 healthy subjects in decade age bands: 10-19, 20-29, 30-39, 40-49, 50-59, 60-69, 70-79, 80-89. The compensatory eye movement response to a small, unpredictable, abrupt head rotation (head impulse) was measured by the ICS impulse prototype system. The same operator delivered every impulse to every subject. Vestibulo-ocular reflex gain decreased at high head velocities, but was largely unaffected by age into the 80- to 89-year age group. There were some small but systematic differences between the two directions of head rotation, which appear to be largely due to the fact that in this study only the right eye was measured. The results are considered in relation to recent evidence about the effect of age on VOR performance. These normative values allow the results of any particular patient to be compared to the values of healthy people in their age range and so allow, for example, detection of whether a patient has a bilateral vestibular loss. VOR gain, as measured directly by the eye movement response to head rotation, seems largely unaffected by aging.

P36. Using opioid-induced bilateral vestibular dysfunction to validate the Head Impulse Testing Device – Functional Test (HITD-FT)

Introduction Patients with bilateral vestibular dysfunction cannot fully compensate passive head rotations with eye movements, and therefore experience oscillopsia, making everyday activities, such as walking or driving harder to undertake. Their dynamic vision during passive head movements depends on their residual vestibulo-ocular reflex (VOR) function and on re-fixation saccades. The Head Impulse Testing Device – Functional Test (HITD-FT) is a recently proposed and innovative technique for assessing dynamic vision during passive high-acceleration head rotations, mimicking natural everyday movements. Goals To validate the HITD-FT as a tool to assess the performance of the vestibulo-ocular reflex (VOR) and the effect of re-fixation saccades on the overall dynamic visual function in opioid-induced bilateral vestibular dysfunction. Materials and methods The opioid remifentanil was continuously administrated in 14 healthy men (median age 26 years, range 21–31) in order to reversibly induce a bilateral vestibular impairment. Each subject was tested with the HITD-FT before and during opioid administration. In each test, passive, unpredictable, high-acceleration (2000–7000°/s 2 ) and small amplitude (10–20°) the ects-FT score mirrorice comched 300°/srdmic visual function matters. Unctionality, i.e. disturbing oscillopsia lity to com head rotations where applied while subjects fixated a visual stimulus. The visual stimulus consisted of a standard Landolt ring and appeared on a screen 80 ± 2 ms after head acceleration reached 300°/s 2 . Subjects were asked to identify the orientation of the ring and the provided answers were analyzed together with eye and head movements recorded with EyeSeeCam system. Results Before opioid application, VOR and dynamic reading performances were intact (head-impulse gain: 0.87 ± 0.08, mean ± SD; HITD-FT rate of correct answers: 90 ± 9%). The opioid administration induced impairment in the VOR function (head-impulse gain 0.63 ± 0.19) and in dynamic reading (HITD-FT 26 ± 15%) in 12/14 subjects. HITD-FT scores correlated with head-impulse gain impairment ( R = 0.63, p = 0.03) and with gain difference (before/during opioid R = −0.64, p = 0.02). One subject had non-pathological head-impulse gain (0.82 ± 0.03) and high HITD-FT score (92%). One subject could read (93%) despite a low head-impulse gain (0.59 ± 0.03) performing re-fixation saccades. Summary Our study suggests that the recently proposed HITD-FT is an appropriate method to document the combined effect of VOR performance and re-fixation saccades in vestibular dysfunction. Testing dynamic vision with head movement characteristics closely related to subjects’ daily activities makes the HITD-FT a suitable tool for assessing overall dynamic visual performance, e.g., to monitor progress during vestibular rehabilitation.

An Isolated Semi-intact Preparation of the Mouse Vestibular Sensory Epithelium for Electrophysiology and High-resolution Two-photon Microscopy

Understanding vestibular hair cells function under normal conditions, or how trauma, disease, and aging disrupt this function is a vital step in the development of preventative approaches and/or novel therapeutic strategies. However, the majority of studies looking at abnormal vestibular function have not been at the cellular level but focused primarily on behavioral assays of vestibular dysfunction such as gait analyses and vestibulo-ocular reflex performance. While this work has yielded valuable data about what happens when things go wrong, little information is gleaned regarding the underlying causes of dysfunction. Of the studies that focus on the cellular and subcellular processes that underlie vestibular function, most have relied on acutely isolated hair cells, devoid of their synaptic connections and supporting cell environment. Therefore, a major technical challenge has been access to the exquisitely sensitive vestibular hair cells in a preparation that is least disrupted, physiologically. Here we demonstrate a semi-intact preparation of the mouse vestibular sensory epithelium that retains the local micro-environment including hair cell/primary afferent complexes.

An Isolated Semi-intact Preparation of the Mouse Vestibular Sensory Epithelium for Electrophysiology and High-resolution Two-photon Microscopy

Understanding vestibular hair cells function under normal conditions, or how trauma, disease, and aging disrupt this function is a vital step in the development of preventative approaches and/or novel therapeutic strategies. However, the majority of studies looking at abnormal vestibular function have not been at the cellular level but focused primarily on behavioral assays of vestibular dysfunction such as gait analyses and vestibulo-ocular reflex performance. While this work has yielded valuable data about what happens when things go wrong, little information is gleaned regarding the underlying causes of dysfunction. Of the studies that focus on the cellular and subcellular processes that underlie vestibular function, most have relied on acutely isolated hair cells, devoid of their synaptic connections and supporting cell environment. Therefore, a major technical challenge has been access to the exquisitely sensitive vestibular hair cells in a preparation that is least disrupted, physiologically. Here we demonstrate a semi-intact preparation of the mouse vestibular sensory epithelium that retains the local micro-environment including hair cell/primary afferent complexes.

A Device for the Functional Evaluation of the VOR in Clinical Settings

We developed the head impulse testing device (HITD) based on an inertial sensing system allowing to investigate the functional performance of the rotational vestibulo-ocular reflex (VOR) by testing its gaze stabilization ability, independently from the subject’s visual acuity, in response to head impulses at different head angular accelerations ranging from 2000 to 7000 deg/s2. HITD was initially tested on 22 normal subjects, and a method to compare the results from a single subject (patient) with those from controls was set up. As a pilot study, we tested the HITD in 39 dizzy patients suffering, non-acutely, from different kinds of vestibular disorders. The results obtained with the HITD were comparable with those from the clinical head impulse test (HIT), but an higher number of abnormalities was detectable by HITD in the central vestibular disorders group. The HITD appears to be a promising tool for detecting abnormal VOR performance while providing information on the functional performance of the rotational VOR, and can provide a valuable assistance to the clinical evaluation of patients with vestibular disorders.

Bidirectional Plasticity Gated by Hyperpolarization Controls the Gain of Postsynaptic Firing Responses at Central Vestibular Nerve Synapses

Linking synaptic plasticity with behavioral learning requires understanding how synaptic efficacy influences postsynaptic firing in neurons whose role in behavior is understood. Here, we examine plasticity at a candidate site of motor learning: vestibular nerve synapses onto neurons that mediate reflexive movements. Pairing nerve activity with changes in postsynaptic voltage induced bidirectional synaptic plasticity in vestibular nucleus projection neurons: long-term potentiation relied on calcium-permeable AMPA receptors and postsynaptic hyperpolarization, whereas long-term depression relied on NMDA receptors and postsynaptic depolarization. Remarkably, both forms of plasticity uniformly scaled synaptic currents evoked by pulse trains, and these changes in synaptic efficacy were translated into linear increases or decreases in postsynaptic firing responses. Synapses onto local inhibitory neurons were also plastic but expressed only long-term depression. Bidirectional, linear gain control of vestibular nerve synapses onto projection neurons provides a plausible mechanism for motor learning underlying adaptation of vestibular reflexes.

Synaptic Plasticity in Medial Vestibular Nucleus Neurons: Comparison with Computational Requirements of VOR Adaptation

BackgroundVestibulo-ocular reflex (VOR) gain adaptation, a longstanding experimental model of cerebellar learning, utilizes sites of plasticity in both cerebellar cortex and brainstem. However, the mechanisms by which the activity of cortical Purkinje cells may guide synaptic plasticity in brainstem vestibular neurons are unclear. Theoretical analyses indicate that vestibular plasticity should depend upon the correlation between Purkinje cell and vestibular afferent inputs, so that, in gain-down learning for example, increased cortical activity should induce long-term depression (LTD) at vestibular synapses.Methodology/Principal FindingsHere we expressed this correlational learning rule in its simplest form, as an anti-Hebbian, heterosynaptic spike-timing dependent plasticity interaction between excitatory (vestibular) and inhibitory (floccular) inputs converging on medial vestibular nucleus (MVN) neurons (input-spike-timing dependent plasticity, iSTDP). To test this rule, we stimulated vestibular afferents to evoke EPSCs in rat MVN neurons in vitro. Control EPSC recordings were followed by an induction protocol where membrane hyperpolarizing pulses, mimicking IPSPs evoked by flocculus inputs, were paired with single vestibular nerve stimuli. A robust LTD developed at vestibular synapses when the afferent EPSPs coincided with membrane hyperpolarisation, while EPSPs occurring before or after the simulated IPSPs induced no lasting change. Furthermore, the iSTDP rule also successfully predicted the effects of a complex protocol using EPSP trains designed to mimic classical conditioning.ConclusionsThese results, in strong support of theoretical predictions, suggest that the cerebellum alters the strength of vestibular synapses on MVN neurons through hetero-synaptic, anti-Hebbian iSTDP. Since the iSTDP rule does not depend on post-synaptic firing, it suggests a possible mechanism for VOR adaptation without compromising gaze-holding and VOR performance in vivo.

Somatosensory induced adaptation in the human otolith-ocular reflex

The vestibulo-ocular reflex (VOR) generates smooth eye movements that compensate for head movements to ensure gaze stabilization during head rotation. The VOR is under adaptive control and corrects VOR performance when visual-vestibular mismatch arises during head movement. During normal visual-vestibular interaction, cooperation between the VOR and vision results in stabilization of the retinal image. Adaptive VOR recalibration occurs when visual-vestibular mismatch arises through the manipulation of visual feedback during head movement. In consideration of how important VOR is in stabilizing gaze, it could be predicted that when VOR is lost, patients would be severely disabled by retinal image movement due to head movement. The vestibular center uses substitutes such as visual and somatosensory information to compensate for lost vestibular signals. In the present study, to investigate the contribution of somatosensory signals to VOR, especially the otolith-ocular reflex (OOR), we examined the plasticity of the OOR using vestibular-somatosensory interaction and the effect of the adaptive plasticity of the OOR by somatosensory stimulation using alternative pressure stimulation on the outer side of the bilateral upper arms for 20 seconds. To study the influence of somatosensory input on the otolith-ocular reflex, we used sinusoidal off-vertical axis rotation at a tilt angle of 30 degrees. Subjects were rotated with their eyes open in complete darkness at frequencies of 0.32 Hz with a maximum angular velocity of 60 o/s. Results showed a significant gain decrement in EVAR after somatosensory adaptive stimulation, whereas gain change was not significantly different in OVAR. We suggest that somatosensory input had an additive effect on the otolith-ocular reflex in this study. This result could be applied to vestibular rehabilitation using somatosensory input.

体性感覚入力が半規管‐眼反射に及ぼす影響

The vestibulo-ocular reflex (VOR) generates smooth eye movements that are compensatory for head movements to ensure gaze stabilization during head rotations. The VOR is under adaptive control that corrects VOR performance when visual-vestibular mismatch arises during head movement. During normal visual-vestibular interaction, cooperation between the VOR and vision results in stabilization of the retinal image. Adaptive VOR recalibration occurs when a visual-vestibular mismatch arises through the manipulation of visual feedback during head movement or by lesion-induced modification of vestibular input. Considering how important VOR is in stabilizing gaze, one could predict that when VOR is lost, patients would be severely disabled by retinal image movement due to head movement. To compensate for vestibular deficits, the vestibular system uses other substitutes such as visual and somatosensory information for the lost vestibular signals. To investigate the contribution of somatosensory signal to the VOR, especially the semicircular-ocular reflex (ScOR), we examined the plasticity of the ScOR using vestibular-somatosensory interaction and the effect of the adaptive plasticity of the ScOR by somatosensory stimulation. We demonstrated a reasonably consistent effect on adaptation of ScOR gain using a somatosensory stimulation paradigm. Our data suggest that the ScOR and somatosensory signals share common neural pathways in such a way that a change in the synaptic efficacy of one pathway is accompanied by a change in the other. The role of a neural storage system that receives input from both the semicircular canals and the somatosensory system to maintain a spatial orientation is discussed.