Galvanic Vestibular Stimulation: a new model of placebo-induced nausea.

OBJECTIVE: Traditional rotation-based models of placebo nausea are limited because they do not have vehicle settings and are tied to their context. The present study introduces a new model for examining placebo-induced nausea in the laboratory that overcomes these limitations, namely, Galvanic Vestibular Stimulation (GVS). GVS stimulates the vestibular system to cause nausea through sensory mismatch with visual cues and importantly has a non-nauseating placebo setting. Using this, we tested whether conditioning could elicit placebo nausea when participants were later exposed to placebo stimulation as well as whether this placebo nausea was generalised across contexts--something that is extremely difficult to test with rotation-based models of placebo nausea. METHODS: Thirty healthy undergraduate students were randomised to receive either placebo GVS (controls) or active GVS during training (Context-Consistent and Context-Change). On test, all groups received placebo GVS. The controls and Context-Consistent groups were tested in the same context as training, whereas the Context-Change group was tested in a new context. RESULTS: Participants conditioned with nausea during training had significantly higher nausea symptom ratings after placebo stimulation on test than those given no conditioning. This placebo-induced nausea also generalised to a novel test context with no differences observed between the Context-Change and Context-Consistent groups. CONCLUSION: GVS provides a new model of placebo-induced nausea that overcomes limitations to traditional rotation-based paradigms. Future studies should use this device to explore the effect of instructions and conditioning on the development of placebo nausea and to assess the efficacy of conditioning-based interventions for clinical use.

Vestibular function after vestibular neuritis.

OBJECTIVE: To measure horizontal semicircular canal function over days, weeks, and months after an acute attack of vestibular neuritis. DESIGN: The video head impulse test (vHIT) was used to measure the eye movement response to small unpredictable passive head turns at intervals after the attack. STUDY SAMPLE: Two patients diagnosed with acute right unilateral vestibular neuritis. RESULTS: There was full restoration of horizontal canal function in one patient (A) as shown by the return of the slow phase eye velocity response to unpredictable head turns, while in the other patient (B) there was little or no recovery of horizontal canal function. Instead this second patient generated covert saccades during head turns. CONCLUSION: Despite the objective evidence of their very different recovery patterns, both patients reported, at the final test, being happy and feeling well recovered, even though in one of the patients there was clear absence of horizontal canal function. The results indicate covert saccades seem a successful way of compensating for loss of horizontal canal function after unilateral vestibular neuritis. Factors other than recovery of the slow phase eye velocity are significant for patient recovery.

Validation of centrifugation as a countermeasure for otolith deconditioning during spaceflight: preliminary data of the ESA SPIN study.

In the framework of further space exploration, countermeasures to combat the drawbacks of human space flights are essential. The present study focuses on the influence of microgravity on the otolith-ocular reflex and aims to test the hypothesis of artificial gravity being an adequate countermeasure for the deconditioning of the aforementioned reflex. The so-called SPIN study, commissioned by the European Space Agency, can be considered as a control experiment in the broad sense for the Neurolab mission (STS-90) during which 4 crewmembers of the space shuttle were subjected to in-flight centrifugation on the visual and vestibular investigation system (VVIS). After their nearly 16-day mission, they did not suffer from orthostatic intolerance and spatial disorientation. In addition, the relevant parameters of the otolith-ocular interaction remained unaffected. For this study cosmonauts from a long duration stay in the International Space Station that were not centrifuged in-flight were tested on the VVIS (1 g centripetal interaural acceleration) on 6 different days. Three measurements were taken about 1.5-2 months prior to launch and 3 were taken at 1, 4 and 9 days after return from space. Ocular counter-rolling was measured before, during and after rotation on the VVIS using infrared video goggles and compared pair wise using Friedman tests. The perception of verticality was monitored using an ultrasound system for perceptual evaluation. The preliminary results of 4 cosmonauts showed a surprisingly large inter-individual variability of the measurements. Although OCR and perception of verticality appeared to be influenced overall by the exposure to microgravity, the wide variability among the cosmonauts obscured any statistical significance, in particular due to one cosmonauts being inconsistent with the other 3. Despite the specificity of the tests under normal conditions, the diverse response to spaceflight of our subjects exposes the complexity of the peripheral and central neural adaptive processes.

Prospective memory in the ICU: the effect of visual cues on task execution in a representative simulation.

Despite the potential dangers of clinical tasks being forgotten, few researchers have investigated prospective memory (PM) - the ability to remember to execute future tasks - in health-care contexts. Visual cues help people remember to execute intentions at the appropriate moment. Using an intensive care unit simulator, we investigated whether nurses' memory for future tasks improves when visual cues are present, and how nurses manage PM demands. Twenty-four nurses participated in a 40-minute scenario simulating the start of a morning shift. The scenario included eight PM tasks. The presence or absence of a visually conspicuous cue for each task was manipulated. The presence of a visual cue improved recall compared to no cue (64% vs. 50%, p = 0.03 one-tailed, η(p)(2) = 0.15). Nurses used deliberate reminders to manage their PM demands. PM in critical care might be supported by increasing the visibility of cues related to tasks. PRACTITIONER SUMMARY: Nurses must remember to execute multiple future tasks to ensure patient safety. We investigated the effect of visual cues on nurses' ability to remember future tasks. Experimental manipulation of cues in a representative intensive care unit simulation indicated that visual cues increase the likelihood that future tasks are executed.

Posterior semicircular canal occlusion for intractable benign positional vertigo: outcome in 55 ears in 53 patients operated upon over 20 years.

OBJECTIVE: To report the outcome of posterior semicircular canal occlusion surgery for intractable benign positional vertigo, regarding vertigo cure rate and hearing and balance outcomes. METHODS: Retrospective review of 53 patients presenting with benign positional vertigo, unresponsive to repositioning manoeuvres, who eventually underwent posterior canal occlusion, over a 20 year period. RESULTS: From 1991 to 2011, 5364 benign positional vertigo patients were treated in our balance disorders clinic; 53 of those who failed to respond to repositioning underwent posterior canal occlusion. All 53 were cured of their benign positional vertigo. Nine suffered some symptomatic permanent hearing loss (>20 dB at low and >25 dB at high frequencies). Ten patients suffered caloric vestibular function deterioration, with mild but permanent subjective imbalance in five; a further 10 patients with no post-operative caloric test changes also had some permanent imbalance. Benign positional vertigo later developed in the operated ear lateral canal in two patients and in the opposite ear posterior canal in eight patients. Two patients needed bilateral sequential posterior canal occlusion. CONCLUSION: Posterior canal occlusion is a highly effective treatment for intractable benign positional vertigo, with what is probably an acceptable risk to hearing and balance: five of six patients will have no hearing problem and nine of 10 no balance problem after surgery.

The basis for using bone-conducted vibration or air-conducted sound to test otolithic function.

Extracellular single neuron recordings of primary vestibular neurons in Scarpa's ganglion in guinea pigs show that low-intensity 500 Hz bone-conducted vibration (BCV) or 500 Hz air-conducted sound (ACS) activate a high proportion of otolith irregular neurons from the utricular and saccular maculae but few semicircular canal neurons. In alert guinea pigs, and humans, 500 Hz BCV elicits otolith-evoked eye movements. In humans, it also elicits a myogenic potential on tensed sternocleidomastoid muscles. Although BCV and ACS activate both utricular and saccular maculae, it is possible to probe the functional status of these two sense organs separately because of their differential neural projections. Saccular neurons have a strong projection to neck muscles and a weak projection to the oculomotor system. Utricular afferents have a strong projection to eye muscles. So measuring oculomotor responses to ACS and BCV predominantly probes utricular function, while measuring neck muscle responses to these stimuli predominantly probes saccular function.

The video head impulse test: diagnostic accuracy in peripheral vestibulopathy.

BACKGROUND: The head impulse test (HIT) is a useful bedside test to identify peripheral vestibular deficits. However, such a deficit of the vestibulo-ocular reflex (VOR) may not be diagnosed because corrective saccades cannot always be detected by simple observation. The scleral search coil technique is the gold standard for HIT measurements, but it is not practical for routine testing or for acute patients, because they are required to wear an uncomfortable contact lens. OBJECTIVE: To develop an easy-to-use video HIT system (vHIT) as a clinical tool for identifying peripheral vestibular deficits. To validate the diagnostic accuracy of vHIT by simultaneous measures with video and search coil recordings across healthy subjects and patients with a wide range of previously identified peripheral vestibular deficits. METHODS: Horizontal HIT was recorded simultaneously with vHIT (250 Hz) and search coils (1,000 Hz) in 8 normal subjects, 6 patients with vestibular neuritis, 1 patient after unilateral intratympanic gentamicin, and 1 patient with bilateral gentamicin vestibulotoxicity. RESULTS: Simultaneous video and search coil recordings of eye movements were closely comparable (average concordance correlation coefficient r(c) = 0.930). Mean VOR gains measured with search coils and video were not significantly different in normal (p = 0.107) and patients (p = 0.073). With these groups, the sensitivity and specificity of both the reference and index test were 1.0 (95% confidence interval 0.69-1.0). vHIT measures detected both overt and covert saccades as accurately as coils. CONCLUSIONS: The video head impulse test is equivalent to search coils in identifying peripheral vestibular deficits but easier to use in clinics, even in patients with acute vestibular neuritis.

Testing human otolith function using bone-conducted vibration.

Bone-conducted vibration of the forehead, in the midline at the hairline (Fz) causes linear acceleration stimulation of both mastoids and results in an ocular vestibular-evoked myogenic potential (oVEMP), recorded by surface electromyogram (EMG) electrodes just beneath the eyes. The early n10 component of the oVEMP is symmetrical in healthy subjects, absent in patients with bilateral vestibular loss, and in patients after unilateral vestibular loss (uVL) n10 is small or absent on the side contralateral to the uVL, but of normal amplitude on the side contralateral to the healthy ear. The n10 component probably reflects mainly otolithic function, since in the guinea pig, primary otolith irregular neurons are selectively activated by bone-conducted vibration (BCV) at low intensities (0.1 g), whereas semicircular canal primary afferents are not activated even at high intensities (10 g).

Ocular vestibular evoked myogenic potentials to bone conducted vibration of the midline forehead at Fz in healthy subjects.

OBJECTIVE: To provide the empirical basis for using ocular vestibular evoked myogenic potentials (oVEMPS) in response to Fz bone conducted vibration (BCV) stimulation to indicate vestibular function in human subjects. To show the generality of the response by testing a large number of unselected healthy subjects across a wide age range and the repeatability of the response within subjects. To provide evidence that the response depends on otolithic function. METHODS: The early negative component (n10) of the oVEMP to brief BCV of the forehead, in the midline at the hairline (Fz) is recorded by surface EMG electrodes just beneath the eyes. We used a Bruel and Kjaer 4810 Mini-Shaker or a light tap with a tendon hammer to provide adequate BCV stimuli to test a large number (67) of unselected healthy people to quantify the individual differences in n10 magnitude, latency and symmetry to Fz BCV. A Radioear B-71 bone oscillator at Fz is not adequate to elicit a reliable n10 response. RESULTS: The n10 oVEMP response showed substantial differences in amplitude between subjects, but is repeatable within subjects. n10 is of equal magnitude in both eyes with an average asymmetry around 11%. The average n10 amplitude for Mini Tone Burst BCV is 8.47microV+/-4.02 (sd), the average latency is 10.35ms+/-0.63 (sd). The amplitude of n10 decreases and its latency increases with age. CONCLUSIONS: oVEMPs are a new reliable, repeatable test to indicate vestibular and probably otolithic function. SIGNIFICANCE: This study shows the optimum conditions for recording oVEMPs and provides baseline values for individual differences and asymmetry. oVEMPs can be measured in senior subjects without difficulty.

Ocular vestibular evoked myogenic potentials in response to bone-conducted vibration of the midline forehead at Fz. A new indicator of unilateral otolithic loss.

If a patient, who is lying supine and looking upward, is given bone-conducted vibration (BCV) of the forehead at the hairline in the midline (Fz) with a clinical reflex hammer or a powerful bone conduction vibrator, short-latency surface potentials called ocular vestibular evoked myogenic potentials (oVEMP) can be recorded from just beneath the eyes. The early negative (excitatory) component (n10) is approximately equal in amplitude for both eyes in healthy subjects, but in patients with unilateral vestibular loss, the n10 component is significantly asymmetrical under the 2 eyes - the n10 component is small or absent under the eye on the side contralateral to the prior unilateral vestibular nerve removal, but of normal amplitude under the eye on the side contralateral to the healthy ear. The n10 component of the oVEMP response to BCV at Fz stimuli reflects vestibular and probably mainly otolithic function via crossed otolithic-ocular pathways, and so n10 asymmetry is a new way of identifying the affected side in patients with unilateral otolithic loss.

Psychophysiological correlates of the inter-individual variability of head movement control in seated humans.

We recently conducted experiments where 24 seated participants were subjected (with eyes closed) to small amplitude, high-jerk impulses of linear acceleration. Responses were distributed as a continuum between two extremes. The "stiff" participants showed little movement of the head relative to the trunk, whereas the "floppy" participants showed a large head rotation in the direction opposite the sled movement. We hypothesized that the stiff behavior resulted from the spontaneous use of an imagined visual frame of reference and undertook this larger-scale study to test that idea. The distribution along the "stiff-floppy" continuum was compared with the scores on psychophysiological tests measuring vividness of imagery, visual field-dependence and motion sickness susceptibility. Multivariate regression analysis revealed that the "stiffness" of individuals was loosely, but significantly related to the vividness of their imagery. However, "stiffness" was not linked to visual field-dependence or motion sickness susceptibility. Even if it explains only 20% of the variance of the data, the increase of "stiffness" with vividness of imagery fits our hypothesis. With eyes closed, stiff people may use imagined external visual cues to stabilize their head and trunk. Floppy people, who are poorer imagers, may rely more on "egocentric", proprioceptive and vestibular inputs.

Patient and normal three-dimensional eye-movement responses to maintained (DC) surface galvanic vestibular stimulation.

HYPOTHESIS: That disease or dysfunction of vestibular end organs in human patients will reduce or eliminate the contribution of the affected end organs to the total eye-movement response to DC surface galvanic vestibular stimulation (GVS). BACKGROUND: It was assumed that DC GVS (at current of 5 mA) stimulates all vestibular end organs, an assumption that is strongly supported by physiological evidence, including the activation of primary vestibular afferent neurons by galvanic stimulation. Previous studies also have described the oculomotor responses to vestibular activation. Stimulation of individual semicircular canals results in eye movements parallel to the plane of the stimulated canal, and stimulation of the utricular macula produces changes in ocular torsional position. It was also assumed that the total three-dimensional eye-movement response to GVS is the sum of the contributions of the oculomotor drive of all the vestibular end organs. If a particular vestibular end organ were to be diseased or dysfunctional, it was reasoned that its contribution to the GVS-induced oculomotor response would be reduced or absent and that patients thus affected would have a systematic difference in their GVS-induced oculomotor response compared with the response of normal healthy individuals. METHODS: Three-dimensional video eye-movement recording was carried out in complete darkness on normal healthy subjects and patients with various types of vestibular dysfunction, as diagnosed by independent vestibular clinical tests. The eye-movement response to long-duration bilateral and unilateral surface GVS was measured. RESULTS: The pattern of horizontal, vertical, and torsional eye velocity and eye position during GVS of patients independently diagnosed with bilateral vestibular dysfunction, unilateral vestibular dysfunction, CHARGE syndrome (semicircular canal hypoplasia), semicircular canal occlusion, or inferior vestibular neuritis differed systematically from the responses of normal healthy subjects in ways that corresponded to the expectations from the conceptual approach of the study. CONCLUSION: The study reports the first data on the differences between the normal response to GVS and those of patients with a number of clinical vestibular conditions including unilateral vestibular loss, canal block, and vestibular neuritis. The GVS-induced eye-movement patterns of patients with vestibular dysfunction are consistent with the reduction or absence of oculomotor contribution from the end organs implicated in their particular disease condition.

Convergence reduces ocular counterroll (OCR) during static roll-tilt.

When humans are roll-tilted around the naso-occipital axis, both eyes roll or tort in the opposite direction to roll-tilt, a phenomenon known as ocular counterroll (OCR). While the magnitude of OCR is primarily determined by vestibular, somatosensory, and proprioceptive input, direction of gaze also plays a major role. The aim of this study was to measure the interaction between some of these factors in the control of OCR. Videooculography was used to measure 3D eye position during maintained whole body (en bloc) static roll-tilt in darkness, while subjects fixated first on a distant (at 130 cm) and then a near (at 30 cm) head-fixed target aligned with the subject's midline. We found that while converging on the near target, human subjects displayed a significant reduction in OCR for both directions of roll-tilt--i.e. the interaction between OCR and vergence was not simple addition or subtraction of torsion induced by vergence with torsion induced by roll-tilt. To remove the possibility that the OCR reduction may be associated with the changed horizontal position of the eye in the orbit during symmetric convergence, we ran an experiment using asymmetric convergence in which the distant and near targets were aligned directly in front of one eye. We found the magnitude of OCR in this asymmetric convergence case was also reduced for near viewing by about the same amount as in the symmetric vergence condition, confirming that the convergence command rather than horizontal position of the eye underlies the OCR reduction, since there was no horizontal movement of the aligned eye in the orbit between fixation on the distant and near targets. Increasing vergence from 130 to 30 cm reduced OCR gain by around 35% on average. That reduction was equal in both eyes and occurred in both the symmetric and asymmetric convergence conditions. These results demonstrate the important role vergence plays in determining ocular counterroll during roll-tilt and may support the contention that vergence acts to reduce the conflict facing a stereopsis-generating mechanism.

Variability in the control of head movements in seated humans: a link with whiplash injuries?

The aim of this study was to determine how context and on-line sensory information are combined to control posture in seated subjects submitted to high-jerk, passive linear accelerations. Subjects were seated with eyes closed on a servo-controlled linear sled. They were asked to relax and received brief accelerations either sideways or in the fore-aft direction. The stimuli had an abrupt onset, comparable to the jerk experienced during a minor car collision. Rotation and translation of the head and body were measured using an Optotrak system. In some of the subjects, surface electromyographic (EMG) responses of selected neck and/or back muscles were recorded simultaneously. For each subject, responses were highly stereotyped from the first trial, and showed little sign of habituation or sensitisation. Comparable results were obtained with sideways and fore-aft accelerations. During each impulse, the head lagged behind the trunk for several tens of milliseconds. The subjects' head movement responses were distributed as a continuum in between two extreme categories. The 'stiff' subjects showed little rotation or translation of the head relative to the trunk for the whole duration of the impulse. In contrast, the 'floppy' subjects showed a large roll or pitch of the head relative to the trunk in the direction opposite to the sled movement. This response appeared as an exaggerated 'inertial' response to the impulse. Surface EMG recordings showed that most of the stiff subjects were not contracting their superficial neck or back muscles. We think they relied on bilateral contractions of their deep, axial musculature to keep the head-neck ensemble in line with the trunk during the movement. About half of the floppy subjects displayed reflex activation of the neck muscles on the side opposite to the direction of acceleration, which occurred before or during the head movement and tended to exaggerate it. The other floppy subjects seemed to rely on only the passive biomechanical properties of their head-neck ensemble to compensate for the perturbation. In our study, proprioception was the sole source of sensory information as long as the head did not move. We therefore presume that the EMG responses and head movements we observed were mainly triggered by the activation of stretch receptors in the hips, trunk and/or neck. The visualisation of an imaginary reference in space during sideways impulses significantly reduced the head roll exhibited by floppy subjects. This suggests that the adoption by the central nervous system of an extrinsic, 'allocentric' frame of reference instead of an intrinsic, 'egocentric' one may be instrumental for the selection of the stiff strategy. The response of floppy subjects appeared to be maladaptive and likely to increase the risk of whiplash injury during motor vehicle accidents. Evolution of postural control may not have taken into account the implications of passive, high-acceleration perturbations affecting seated subjects.

Semicircular canal occlusion causes permanent VOR changes.

We measured the guinea pig horizontal vestibulo-ocular reflex (hVOR) to high acceleration impulsive head rotations following a unilateral lateral semicircular canal (LSCC) occlusion. We found a significant hVOR deficit for rotations toward the side of the occluded LSCC and this deficit did not show systematic changes over 3 months. We considered the LSCC nerve was still functional as shown by the normal appearance of the crista of the LSCC ampulla and also electrical stimulation of the LSCC. We conclude that the VOR during angular acceleration in response to high acceleration shows no adaptive plasticity following a unilateral LSCC occlusion.

Electrophysiological evidence for vestibular activation of the guinea pig hippocampus.

Vestibular information modulates hippocampal activity for spatial processing and place cell firing. However, evidence of a purely vestibular stimulus modulating hippocampal activity is confounded as most studies use stimuli containing somatosensory and visual components. In the present study, high-frequency electrical stimulation of specific vestibular sensory regions of the right labyrinth in anaesthetized guinea pigs induced an evoked field potential in the hippocampal formation bilaterally with a latency of about 40 ms following stimulation onset. Field potentials localized in the hippocampal formation occurred with stimulus current parameters that were too small to produce eye movements. This provides direct electrophysiological evidence of vestibular input to the hippocampus.