Assessment of vestibulo-ocular reflex and its adaptation during stop-and-go car rides in motion sickness susceptible passengers.

Motion sickness is a physiological condition that negatively impacts a person's comfort and will be an emerging condition in autonomous vehicles without proper countermeasures. The vestibular system plays a key role in the origin of motion sickness. Understanding the susceptibility and (mal) adaptive mechanisms of the highly integrated vestibular system is a prerequisite for the development of countermeasures. We hypothesize a differential association between motion sickness and vestibular function in healthy individuals with and without susceptibility for motion sickness. We quantified vestibular function by measuring the high-frequency vestibulo-ocular reflex (VOR) using video head impulse testing (vHIT) in 17 healthy volunteers before and after a 11 min motion sickness-inducing naturalistic stop-and-go car ride on a test track (Dekra Test Oval, Klettwitz, Germany). The cohort was classified as motion sickness susceptible (n = 11) and non-susceptible (n = 6). Six (out of 11) susceptible participants developed nausea symptoms, while a total of nine participants were free of these symptoms. The VOR gain (1) did not differ significantly between participant groups with (n = 8) and without motion sickness symptoms (n = 9), (2) did not differ significantly in the factor time before and after the car ride, and showed no interaction between symptom groups and time, as indicated by a repeated measures ANOVA (F(1,15) = 2.19, p = 0.16. Bayesian inference confirmed that there was "anecdotal evidence" for equality of gain rather than difference across groups and time (BF10 < 0.77). Our results suggest that individual differences in VOR measures or adaptation to motion sickness provocative stimuli during naturalistic stop-and-go driving cannot predict motion sickness susceptibility or the likelihood of developing motion sickness.

Unstable Gaze in Functional Dizziness: A Contribution to Understanding the Pathophysiology of Functional Disorders.

Objective: We are still lacking a pathophysiological mechanism for functional disorders explaining the emergence and manifestation of characteristic, severely impairing bodily symptoms like chest pain or dizziness. A recent hypothesis based on the predictive coding theory of brain function suggests that in functional disorders, internal expectations do not match the actual sensory body states, leading to perceptual dysregulation and symptom perception. To test this hypothesis, we investigated the account of internal expectations and sensory input on gaze stabilization, a physiologically relevant parameter of gaze shifts, in functional dizziness. Methods: We assessed gaze stabilization in eight functional dizziness patients and 11 healthy controls during two distinct epochs of large gaze shifts: during a counter-rotation epoch (CR epoch), where the brain can use internal models, motor planning, and resulting internal expectations to achieve internally driven gaze stabilization; and during an oscillation epoch (OSC epoch), where, due to terminated motor planning, no movement expectations are present, and gaze is stabilized by sensory input alone. Results: Gaze stabilization differed between functional patients and healthy controls only when internal movement expectations were involved [F(1,17) = 14.63, p = 0.001, and partial η2 = 0.463]: functional dizziness patients showed reduced gaze stabilization during the CR (p = 0.036) but not OSC epoch (p = 0.26). Conclusion: While sensory-driven gaze stabilization is intact, there are marked, well-measurable deficits in internally-driven gaze stabilization in functional dizziness pointing at internal expectations that do not match actual body states. This experimental evidence supports the perceptual dysregulation hypothesis of functional disorders and is an important step toward understanding the underlying pathophysiology.

Deficient head motor control in functional dizziness: Experimental evidence of central sensory-motor dysfunction in persistent physical symptoms.

Understanding the mechanisms of symptoms that are insufficiently explained by organic dysfunction remains challenging. Recently, it has been proposed that such "functional symptoms" are based on erroneous sensory processing in the central nervous system (CNS), with internal expectations dominating sensory inputs. In a pilot study, we used a head motor control set-up to assess the interplay between sensory input and expectation on the example of patients with functional dizziness. Eight patients and 11 age-matched healthy controls performed large active eye-head gaze shifts towards visual targets in the natural situation and with the head moment of inertia 3.3-fold increased. The latter induces head oscillations and the expected sensory outcome of the movement, estimated in the CNS, does not match the actual sensory input. Head oscillations were assessed in patients and in healthy subjects and compared to prior results from patients with organic disease (vestibular loss and cerebellar ataxia). Head oscillations in patients with functional dizziness were different from those of healthy subjects (F(1,17)=27.26, P<0.001, partial η2=0.62), and similar to those of patients with cerebellar ataxia, and with vestibular loss (F(2,19)=0.56, P=0.58). Even in the natural, unweighted, condition, head oscillations were higher in functional dizziness patients than in healthy subjects (P=0.001). Since an extensive work-up failed to demonstrate any explanatory peripheral vestibular, motor, or cerebellar organic dysfunction, these motor control deficits are a first indication of erroneous interplay between expectations and sensory input in the CNS that could account for persistent physical symptoms.

Vestibulo-Ocular Responses and Dynamic Visual Acuity During Horizontal Rotation and Translation.

Dynamic visual acuity (DVA) provides an overall functional measure of visual stabilization performance that depends on the vestibulo-ocular reflex (VOR), but also on other processes, including catch-up saccades and likely visual motion processing. Capturing the efficiency of gaze stabilization against head movement as a whole, it is potentially valuable in the clinical context where assessment of overall patient performance provides an important indication of factors impacting patient participation and quality of life. DVA during head rotation (rDVA) has been assessed previously, but to our knowledge, DVA during horizontal translation (tDVA) has not been measured. tDVA can provide a valuable measure of how otolith, rather than canal, function impacts visual acuity. In addition, comparison of DVA during rotation and translation can shed light on whether common factors are limiting DVA performance in both cases. We therefore measured and compared DVA during both passive head rotations (head impulse test) and translations in the same set of healthy subjects (n = 7). In addition to DVA, we computed average VOR gain and retinal slip within and across subjects. We observed that during translation, VOR gain was reduced (VOR during rotation, mean ± SD: position gain = 1.05 ± 0.04, velocity gain = 0.97 ± 0.07; VOR during translation, mean ± SD: position gain = 0.21 ± 0.08, velocity gain = 0.51 ± 0.16), retinal slip was increased, and tDVA was worse than during rotation (average rDVA = 0.32 ± 0.15 logMAR; average tDVA = 0.56 ± 0.09 logMAR, p = 0.02). This suggests that reduced VOR gain leads to worse tDVA, as expected. We conclude with speculation about non-oculomotor factors that could vary across individuals and affect performance similarly during both rotation and translation.

Head-Movement-Emphasized Rehabilitation in Bilateral Vestibulopathy.

Objective: Although there is evidence that vestibular rehabilitation is useful for treating chronic bilateral vestibular hypofunction (BVH), the mechanisms for improvement, and the reasons why only some patients improve are still unclear. Clinical rehabilitation results and evidence fromeye-head control in vestibular deficiency suggest that headmovement is a crucial element of vestibular rehabilitation. In this study, we assess the effects of a specifically designed head-movement-based rehabilitation program on dynamic vision, and explore underlying mechanisms. Methods: Two adult patients (patients 1 and 2) with chronic BVH underwent two 4-week interventions: (1) head-movement-emphasized rehabilitation (HME) with exercises based on active head movements, and (2) eye-movement-only rehabilitation (EMO), a control intervention with sham exercises without head movement. In a double-blind crossover design, the patients were randomized to first undergo EMO (patient 1) and-after a 4-week washout-HME, and vice-versa (patient 2). Before each intervention and after a 4-week follow-up patients' dynamic vision, vestibulo-ocular reflex (VOR) gain, as well as re-fixation saccade behavior during passive headmotion were assessed with the head impulse testing device-functional test (HITD-FT). Results: HME, not EMO, markedly improved perception with dynamic vision during passive head motion (HITD-FT score) increasing from 0 to 60% (patient 1) and 75% (patient 2). There was a combination of enhanced VOR, as well as improved saccadic compensation. Conclusion: Head movement seems to be an important element of rehabilitation for BVH. It improves dynamic vision with a combined VOR and compensatory saccade enhancement.

Usability of the Video Head Impulse Test: Lessons From the Population-Based Prospective KORA Study.

Objective: The video head impulse test (vHIT) has become a common examination in the work-up for dizziness and vertigo. However, recent studies suggest a number of pitfalls, which seem to reduce vHIT usability. Within the framework of a population-based prospective study with naïve examiners, we investigated the relevance of previously described technical mistakes in vHIT testing, and the effect of experience and training. Methods: Data originates from the KORA (Cooperative Health Research in the Region of Augsburg) FF4 study, the second follow-up of the KORA S4 population-based health survey. 681 participants were selected in a case-control design. Three examiners without any prior experience were trained in video head impulse testing. VHIT quality was assessed weekly by an experienced neuro-otologist. Restrictive mistakes (insufficient technical quality restricting interpretation) were noted. Based on these results, examiners received further individual training. Results: Twenty-two of the 681 vHITs (3.2%) were not interpretable due to restrictive mistakes. Restrictive mistakes could be grouped into four categories: slippage, i.e., goggle movement relative to the head (63.6%), calibration problems (18.2%), noise (13.6%), and low velocity of the head impulse (4.6%). The overall rate of restrictive mistakes decreased significantly during the study (12% / examiner within the first 25 tested participants and 2.1% during the rest of the examinations, p < 0.0001). Conclusion: Few categories suffice to explain restrictive mistakes in vHIT testing. With slippage being most important, trainers should emphasize the importance of tight goggles. Experience and training seem to be effective in improving vHIT quality, leading to high usability.

Preventing opioid-induced nausea and vomiting: Rest your head and close your eyes?

Although opioid-induced nausea and vomiting (OINV) is common and debilitating, its mechanism is still unclear. Recently, we suggested that opioids affect semicircular canal function and that this leads to a mismatch between canal input and other sensory information during head motion, which triggers OINV. Here, we assess if visual input is relevant for this mismatch. In a randomized-controlled crossover study 14 healthy men (26.9±3.4 years, mean±SD) were tested twice, once blindfolded and once with eyes open, with at least one-day washout. The opioid remifentanil was administered intravenously (0.15 µg/kg/min) for 60 minutes. After a thirty-minutes resting period, subjects' head and trunk were passively moved. Nausea was rated before remifentanil start (T0), before the movement intervention (T30) and after 60 minutes (T60) of administration. At rest (T0, T30), median nausea ratings were zero whether subjects were blindfolded or not. Movement triggered nausea independently of visual input (nausea rating 1.5/3.0 (median/interquartile range) in the blindfolded, 2.5/6 in the eyes-open condition, χ2(1) = 1.3, p = 0.25). As movement exacerbates OINV independently of visual input, a clash between visual and semicircular canal information is not the relevant trigger for OINV. To prevent OINV, emphasis should be put on head-rest, eye-closure is less important.

The effect of vestibulo-ocular reflex deficits and covert saccades on dynamic vision in opioid-induced vestibular dysfunction.

Patients with bilateral vestibular dysfunction cannot fully compensate passive head rotations with eye movements, and experience disturbing oscillopsia. To compensate for the deficient vestibulo-ocular reflex (VOR), they have to rely on re-fixation saccades. Some can trigger "covert" saccades while the head still moves; others only initiate saccades afterwards. Due to their shorter latency, it has been hypothesized that covert saccades are particularly beneficial to improve dynamic visual acuity, reducing oscillopsia. Here, we investigate the combined effect of covert saccades and the VOR on clear vision, using the Head Impulse Testing Device-Functional Test (HITD-FT), which quantifies reading ability during passive high-acceleration head movements. To reversibly decrease VOR function, fourteen healthy men (median age 26 years, range 21-31) were continuously administrated the opioid remifentanil intravenously (0.15 µg/kg/min). VOR gain was assessed with the video head-impulse test, functional performance (i.e. reading) with the HITD-FT. Before opioid application, VOR and dynamic reading were intact (head-impulse gain: 0.87±0.08, mean±SD; HITD-FT rate of correct answers: 90±9%). Remifentanil induced impairment in dynamic reading (HITD-FT 26±15%) in 12/14 subjects, with transient bilateral vestibular dysfunction (head-impulse gain 0.63±0.19). HITD-FT score correlated with head-impulse gain (R = 0.63, p = 0.03) and with gain difference (before/with remifentanil, R = -0.64, p = 0.02). One subject had a non-pathological head-impulse gain (0.82±0.03) and a high HITD-FT score (92%). One subject triggered covert saccades in 60% of the head movements and could read during passive head movements (HITD-FT 93%) despite a pathological head-impulse gain (0.59±0.03) whereas none of the 12 subjects without covert saccades reached such high performance. In summary, early catch-up saccades may improve dynamic visual function. HITD-FT is an appropriate method to assess the combined gaze stabilization effect of both VOR and covert saccades (overall dynamic vision), e.g., to document performance and progress during vestibular rehabilitation.