The Neural Basis for Biased Behavioral Responses Evoked by Galvanic Vestibular Stimulation in Primates.

Noninvasive electrical stimulation of the vestibular system in humans has become an increasingly popular tool with a broad range of research and clinical applications. However, common assumptions regarding the neural mechanisms that underlie the activation of central vestibular pathways through such stimulation, known as galvanic vestibular stimulation (GVS), have not been directly tested. Here, we show that GVS is encoded by VIIIth nerve vestibular afferents with nonlinear dynamics that differ markedly from those predicted by current models. GVS produced asymmetric activation of both semicircular canal and otolith afferents to the onset versus offset and cathode versus anode of applied current, that in turn produced asymmetric eye movement responses in three awake-behaving male monkeys. Additionally, using computational methods, we demonstrate that the experimentally observed nonlinear neural response dynamics lead to an unexpected directional bias in the net population response when the information from both vestibular nerves is centrally integrated. Together our findings reveal the neural basis by which GVS activates the vestibular system, establish that neural response dynamics differ markedly from current predictions, and advance our mechanistic understanding of how asymmetric activation of the peripheral vestibular system alters vestibular function. We suggest that such nonlinear encoding is a general feature of neural processing that will be common across different noninvasive electrical stimulation approaches.SIGNIFICANCE STATEMENT Here, we show that the application of noninvasive electrical currents to the vestibular system (GVS) induces more complex responses than commonly assumed. We recorded vestibular afferent activity in macaque monkeys exposed to GVS using a setup analogous to human studies. GVS evoked notable asymmetries in irregular afferent responses to cathodal versus anodal currents. We developed a nonlinear model explaining these GVS-evoked afferent responses. Our model predicts that GVS induces directional biases in centrally integrated head motion signals and establishes electrical stimuli that recreate physiologically plausible sensations of motion. Altogether, our findings provide new insights into how GVS activates the vestibular system, which will be vital to advancing new clinical and biomedical applications.

Changes in vestibular-related responses to combined noisy galvanic vestibular stimulation and cerebellar transcranial direct current stimulation.

Vestibular nuclei and cerebellar function comprise vestibular neural networks that control vestibular-related responses. However, the vestibular-related responses to simultaneous stimulation of these regions are unclear. This study aimed to examine whether the combination of noisy galvanic vestibular stimulation (nGVS) and cerebellar transcranial direct current stimulation (ctDCS) using a complex transcranial electrical stimulation device alters vestibular-dominant standing stability and vestibulo-ocular reflex (VOR) function. The center of foot pressure (COP) sway and VOR of participants (28 healthy, young adults) were assessed under four conditions of transcranial electrical stimulation using nGVS and ctDCS. The COP was calculated with the participant standing on a soft-foam surface with eyes closed using a force plate to evaluate body sway. VOR measurements were collected via passive head movements and fixation on a target projected onto the front wall using a video head impulse test (vHIT). VOR gain was calculated in six directions using a semicircular canal structure based on the ratio of eye movement to head movement. The nGVS + ctDCS and nGVS + sham ctDCS conditions decreased COP sway compared to the sham nGVS + ctDCS and sham nGVS + sham ctDCS conditions. No significant differences were observed in the main effect of stimulation or the interaction of stimulation and direction on the vHIT parameters. The results of this study suggest that postural stability may be independently affected by nGVS. Our findings contribute to the basic neurological foundation for the clinical application of neurorehabilitation using transcranial electrical stimulation of the vestibular system.

Numerical Simulations of the Epley Maneuver With Clinical Implications.

OBJECTIVES: Canalith repositioning procedures to treat benign paroxysmal positional vertigo are often applied following standardized criteria, without considering the possible anatomical singularities of the membranous labyrinth for each individual. As a result, certain patients may become refractory to the treatment due to significant deviations from the ideal membranous labyrinth, that was considered when the maneuvers were designed. This study aims to understand the dynamics of the endolymphatic fluid and otoconia, within the membranous labyrinth geometry, which may contribute to the ineffectiveness of the Epley maneuver. Simultaneously, the study seeks to explore methods to avoid or reduce treatment failure. DESIGN: We conducted a study on the Epley maneuver using numerical simulations based on a three-dimensional medical image reconstruction of the human left membranous labyrinth. A high-quality micro-computed tomography of a human temporal bone specimen was utilized for the image reconstruction, and a mathematical model for the endolymphatic fluid was developed and coupled with a spherical particle model representing otoconia inside the fluid. This allowed us to measure the position and time of each particle throughout all the steps of the maneuver, using equations that describe the physics behind benign paroxysmal positional vertigo. RESULTS: Numerical simulations of the standard Epley maneuver applied to this membranous labyrinth model yielded unsatisfactory results, as otoconia do not reach the frontside of the utricle, which in this study is used as the measure of success. The resting times between subsequent steps indicated that longer intervals are required for smaller otoconia. Using different angles of rotation can prevent otoconia from entering the superior semicircular canal or the posterior ampulla. Steps 3, 4, and 5 exhibited a heightened susceptibility to failure, as otoconia could be accidentally displaced into these regions. CONCLUSIONS: We demonstrate that modifying the Epley maneuver based on the numerical results obtained in the membranous labyrinth of the human specimen under study can have a significant effect on the success or failure of the treatment. The use of numerical simulations appears to be a useful tool for future canalith repositioning procedures that aim to personalize the treatment by modifying the rotation planes currently defined as the standard criteria.

[Evaluation of semicircular canal and otolith graviceptive pathway function in patients diagnosed with motion sickness disorder based on the diagnostic criteria of the Bárány society].

Objective: To investigate the altered function of the semicircular canal and otolith graviceptive pathway in patients diagnosed with motion sickness disorder (MSD) based on the diagnostic criteria of the Bárány society, and explore its relevance to the pathogenesis of MSD. Methods: This is a case-control study. Twenty patients with MSD and age-and sex-matched healthy controls without a history of MSD from the Department of Neurology of Aerospace Center Hospital between March and August 2022 were recruited. All subjects completed the motion sickness susceptibility questionnaire-short version (MSSQ-short) and the motion sickness assessment questionnaire (MSAQ). Canal function was evaluated using caloric stimulation test and video head impulse test (vHIT), and subjective visual vertical/horizontal (SVV/SVH) and vestibular evoked myogenic potential (VEMP) were employed to assess otolith graviceptive function. Differences in vestibular function and correlations between the two groups were analyzed. Results: Each group consisted of 20 cases (9 males and 11 females). The mean age of the MSD and control groups was (26.9±3.9) years and (27.0±3.4) years, respectively. The scores of MSSQ-short [27.0 (22.5, 38.8) vs 1.2 (0, 3.2), P<0.001] and MSAQ [70.1 (54.5, 78.1) vs 11.8 (11.1, 13.9), P<0.001] were significantly higher in the MSD group compared with those of the control group. Evaluation of canal function revealed a significantly higher incidence of caloric stimulation intolerance in MSD patients (60.0%, 12/20) compared with that of the control group (20.0%, 4/20) (P=0.010). Evaluation of otolith graviceptive pathway indicated no significant difference in SVV, SVH and cervical VEMP (cVEMP) abnormality rates between the two groups (all P>0.05). The ocular VEMP (oVEMP) abnormality rate was significantly higher in the MSD group (55.0%, 11/20) than that of the control group (10.0%, 2/20) (P=0.002), with a delayed P1-wave latency compared with the control group [(18.4±1.2) ms vs (17.6±0.8) ms, P=0.018]. Further correlation analysis revealed that P1-wave latency in oVEMP was positively correlated with MSSQ-short (r=0.486, P=0.002) and MSAQ (r=0.391, P=0.015) scores, and duration of caloric intolerance symptoms (r=0.377, P=0.004). Conclusion: The presence of hypersensitivity to caloric stimulation and delayed latency of otolith function in patients with MSD suggests a "separation" between semicircular canal and otolithic function, which may be related to sensory conflict.

Pediatric Vestibular Assessment: Clinical Framework.

OBJECTIVES: Although vestibular deficits can have severe repercussions on the early motor development in children, vestibular assessment in young children has not yet been routinely integrated in clinical practice and clear diagnostic criteria to detect early vestibular deficits are lacking. In young children, specific adjustments of the test protocol are needed, and normative data are age-dependent as the vestibular pathways mature through childhood. Therefore, this study aims to demonstrate the feasibility of an extensive age-dependent vestibular test battery, to provide pediatric normative data with the concurrent age trends, and to offer a clinical framework for pediatric vestibular testing. DESIGN: This normative study included 133 healthy children below the age of 4 years (mean: 22 mo, standard deviation: 12.3 mo, range: 5-47 mo) without history of hearing loss or vestibular symptoms. Children were divided into four age categories: 38 children younger than 1 year old, 37 one-year olds, 33 two-year olds, and 25 three-year olds. Children younger than 3 years of age were examined with the video Head Impulse Test (vHIT) of the horizontal semicircular canals, cervical vestibular evoked myogenic potentials (cVEMP) with bone conduction stimuli, and the rotatory test at 0.16, 0.04, and 0.01 Hz. In 3-year old children, the vHIT of the vertical semicircular canals and ocular vestibular evoked myogenic potentials (oVEMP) using a minishaker were added to the protocol. RESULTS: The horizontal vHIT appeared to be the most feasible test across age categories, except for children younger than 1-year old in which the success rate was the highest for the cVEMP. Success rates of the rotatory test varied the most across age categories. Age trends were found for the vHIT as the mean vestibulo-ocular reflex (VOR) gain increased significantly with age (r = 0.446, p < 0.001). Concerning the cVEMP, a significant increase with age was found for latency P1 (r = 0.420, p < 0.001), rectified interpeak amplitude P1-N1 (r = 0.574, p < 0.001), and averaged electromyographic (EMG) activity (r = 0.430, p < 0.001), whereas age trends for the latency N1 were less pronounced (r = 0.264, p = 0.004). Overall, the response parameters of the rotatory test did not show significant age effects ( p > 0.01), except for the phase at 0.01 Hz (r = 0.578, p < 0.001). Based on the reported success rates and age-dependent normative vestibular data, straightforward cutoff criteria were proposed (vHIT VOR gain < 0.7, cVEMP rectified interpeak amplitude < 1.3, oVEMP interpeak amplitude < 10 µV) with accompanying clinical recommendations to diagnose early vestibular impairment. CONCLUSIONS: In this large cohort of typically developing children below the age of 4 years, the vHIT and cVEMP were the most feasible vestibular tests. Moreover, the age-dependent normative vestibular data could specify age trends in this group of young children. Finally, based on the current results and clinical experience of more than ten years at the Ghent University Hospital (Belgium), a clinical framework to diagnose early vestibular deficits in young patients is proposed.

[Presbyvestibulopathy in clinical practice.]

With increasing life expectancy, there is an increase in the number of patients with symptoms caused by aging of the vestibular system - presbyvestibulopathy. Presbyvestibulopathy is based on degenerative processes in various parts of the vestibular analyzer - from the semicircular canals and otolithic receptors to the conduction tracts and vestibular nuclei. When examining such patients, it is necessary to take into account the multiplicity of damage to sensory systems in the elderly (impaired balance, vision, cognitive functions). Recognizing presbyvestibulopathy as part of the multifaceted aging process will help to develop comprehensive approaches to the treatment of patients who are always at risk for deterioration of the condition. In this review, we discuss the association of presbyvestibulopathy with neurodegenerative diseases, as well as the correlation between presbyvestibulopathy and balance, visual, cognitive, and psychological disorders.

Parallel evolution of semicircular canal form and sensitivity in subterranean mammals.

The vertebrate vestibular system is crucial for balance and navigation, and the evolution of its form and function in relation to species' lifestyle and mode of locomotion has been the focus of considerable recent study. Most research, however, has concentrated on aboveground mammals, with much less published on subterranean fauna. Here, we explored variation in anatomy and sensitivity of the semicircular canals among 91 mammal species, including both subterranean and non-subterranean representatives. Quantitative phylogenetically informed analyses showed significant widening of the canals relative to radius of curvature in subterranean species. A relative canal width above 0.166 indicates with 95% certainty that a species is subterranean. Fluid-structure interaction modelling predicted that canal widening leads to a substantial increase in canal sensitivity; a reasonably good estimation of the absolute sensitivity is possible based on the absolute internal canal width alone. In addition, phylogenetic comparative modelling and functional landscape exploration revealed repeated independent evolution of increased relative canal width and anterior canal sensitivity associated with the transition to a subterranean lifestyle, providing evidence of parallel adaptation. Our results suggest that living in dark, subterranean tunnels requires good balance and/or navigation skills which may be facilitated by more sensitive semicircular canals.

Adaptive perceptual responses to asymmetric rotation for testing otolithic function.

This study aimed to test the role of the otolithic system in self-motion perception by examining adaptive responses to asymmetric off-axis vertical rotation. Self-movement perception was examined after a conditioning procedure consisting of prolonged asymmetric sinusoidal yaw rotation of the head on a stationary body with hemicycle faster than the other hemicycle. This asymmetric velocity rotation results in a cumulative error in spatial self-motion perception in the upright position that persists over time. Head yaw rotation conditioning was performed in different head positions: in the upright position to activate semicircular canals and in the supine and prone positions to activate both semicircular canals and otoliths with the phase of otolithic stimulation reversed with respect to activation of the semicircular canals. The asymmetric conditioning influenced the cumulative error induced by four asymmetric cycles of whole-body vertical axis yaw rotation. The magnitude of this error depended on the orientation of the head during the conditioning. The error increased by 50% after upright position conditioning, by 100% in the supine position, and decreased by 30% in the prone position. The enhancement and reduction of the perceptual error are attributed to otolithic modulation because of gravity influence of the otoliths during the conditioning procedure in supine and prone positions. These findings indicate that asymmetric velocity otolithic activation induces adaptive perceptual errors such as those induced by semicircular canals alone, and this adaptation may be useful in testing dynamic otolithic perceptual responses under different conditions of vestibular dysfunction.

Genetically eliminating Purkinje neuron GABAergic neurotransmission increases their response gain to vestibular motion.

Purkinje neurons in the caudal cerebellar vermis combine semicircular canal and otolith signals to segregate linear and gravitational acceleration, evidence for how the cerebellum creates internal models of body motion. However, it is not known which cerebellar circuit connections are necessary to perform this computation. We first showed that this computation is evolutionarily conserved and represented across multiple lobules of the rodent vermis. Then we tested whether Purkinje neuron GABAergic output is required for accurately differentiating linear and gravitational movements through a conditional genetic silencing approach. By using extracellular recordings from lobules VI through X in awake mice, we show that silencing Purkinje neuron output significantly alters their baseline simple spike variability. Moreover, the cerebellum of genetically manipulated mice continues to distinguish linear from gravitational acceleration, suggesting that the underlying computations remain intact. However, response gain is significantly increased in the mutant mice over littermate controls. Altogether, these data argue that Purkinje neuron feedback regulates gain control within the cerebellar circuit.

Evolution of arboreality and fossoriality in squirrels and aplodontid rodents: Insights from the semicircular canals of fossil rodents.

Reconstructing locomotor behaviour for fossil animals is typically done with postcranial elements. However, for species only known from cranial material, locomotor behaviour is difficult to reconstruct. The semicircular canals (SCCs) in the inner ear provide insight into an animal's locomotor agility. A relationship exists between the size of the SCCs relative to body mass and the jerkiness of an animal's locomotion. Additionally, studies have also demonstrated a relationship between SCC orthogonality and angular head velocity. Here, we employ two metrics for reconstructing locomotor agility, radius of curvature dimensions and SCC orthogonality, in a sample of twelve fossil rodents from the families Ischyromyidae, Sciuridae and Aplodontidae. The method utilizing radius of curvature dimensions provided a reconstruction of fossil rodent locomotor behaviour that is more consistent with previous studies assessing fossil rodent locomotor behaviour compared to the method based on SCC orthogonality. Previous work on ischyromyids suggests that this group displayed a variety of locomotor modes. Members of Paramyinae and Ischyromyinae have relatively smaller SCCs and are reconstructed to be relatively slower compared to members of Reithroparamyinae. Early members of the Sciuroidea clade including the sciurid Cedromus wilsoni and the aplodontid Prosciurus relictus are reconstructed to be more agile than ischyromyids, in the range of extant arboreal squirrels. This reconstruction supports previous inferences that arboreality was likely an ancestral trait for this group. Derived members of Sciuridae and Aplodontidae vary in agility scores. The fossil squirrel Protosciurus cf. rachelae is inferred from postcranial material as arboreal, which is in agreement with its high agility, in the range of extant arboreal squirrels. In contrast, the fossil aplodontid Mesogaulus paniensis has a relatively low agility score, similar to the fossorial Aplodontia rufa, the only living aplodontid rodent. This result is in agreement with its postcranial reconstruction as fossorial and with previous indications that early aplodontids were more arboreal than their burrowing descendants.

Binocular 3D otolith-ocular reflexes: responses of chinchillas to prosthetic electrical stimulation targeting the utricle and saccule.

From animal experiments by Cohen and Suzuki et al. in the 1960s to the first-in-human clinical trials now in progress, prosthetic electrical stimulation targeting semicircular canal branches of the vestibular nerve has proven effective at driving directionally appropriate vestibulo-ocular reflex eye movements, postural responses, and perception. That work was considerably facilitated by the fact that all hair cells and primary afferent neurons in each canal have the same directional sensitivity to head rotation, the three canals' ampullary nerves are geometrically distinct from one another, and electrically evoked three-dimensional (3D) canal-ocular reflex responses approximate a simple vector sum of linearly independent components representing relative excitation of each of the three canals. In contrast, selective prosthetic stimulation of the utricle and saccule has been difficult to achieve, because hair cells and afferents with many different directional sensitivities are densely packed in those endorgans and the relationship between 3D otolith-ocular reflex responses and the natural and/or prosthetic stimuli that elicit them is more complex. As a result, controversy exists regarding whether selective, controllable stimulation of electrically evoked otolith-ocular reflexes (eeOOR) is possible. Using micromachined, planar arrays of electrodes implanted in the labyrinth, we quantified 3D, binocular eeOOR responses to prosthetic electrical stimulation targeting the utricle, saccule, and semicircular canals of alert chinchillas. Stimuli delivered via near-bipolar electrode pairs near the maculae elicited sustained ocular countertilt responses that grew reliably with pulse rate and pulse amplitude, varied in direction according to which stimulating electrode was employed, and exhibited temporal dynamics consistent with responses expected for isolated macular stimulation.NEW & NOTEWORTHY As the second in a pair of papers on Binocular 3D Otolith-Ocular Reflexes, this paper describes new planar electrode arrays and vestibular prosthesis architecture designed to target the three semicircular canals and the utricle and saccule. With this technological advancement, electrically evoked otolith-ocular reflexes due to stimulation via utricle- and saccule-targeted electrodes were recorded in chinchillas. Results demonstrate advances toward achieving selective stimulation of the utricle and saccule.

Velocity storage: its multiple roles.

Our research described in this article was motivated by the puzzling finding of the Skylab M131 experiments: head movements made while rotating that are nauseogenic and disorienting on Earth are innocuous in a weightless, 0-g environment. We describe a series of parabolic flight experiments that directly addressed this puzzle and discovered the gravity-dependent responses to semicircular canal stimulation, consistent with the principles of velocity storage. We describe a line of research that started in a different direction, investigating dynamic balancing, but ended up pointing to the gravity dependence of angular velocity-to-position integration of semicircular canal signals. Together, these lines of research and the theoretical framework of velocity storage provide an answer to at least part of the M131 puzzle. We also describe recently discovered neural circuits by which active, dynamic vestibular, multisensory, and motor signals are interpreted as either appropriate for action and orientation or as conflicts evoking motion sickness and disorientation.

Activation of GABAB receptors results in excitatory modulation of calyx terminals in rat semicircular canal cristae.

Previous studies have found GABA in vestibular end organs. However, existence of GABA receptors or possible GABAergic effects on vestibular nerve afferents has not been investigated. The current study was conducted to determine whether activation of GABAB receptors affects calyx afferent terminals in the central region of the cristae of semicircular canals. We used patch-clamp recording in postnatal day 13-18 (P13-P18) Sprague-Dawley rats of either sex. Application of GABAB receptor agonist baclofen inhibited voltage-sensitive potassium currents. This effect was blocked by selective GABAB receptor antagonist CGP 35348. Application of antagonists of small (SK)- and large-conductance potassium (BK) channels almost completely blocked the effects of baclofen. The remaining baclofen effect was blocked by cadmium chloride, suggesting that it could be due to inhibition of voltage-gated calcium channels. Furthermore, baclofen had no effect in the absence of calcium in the extracellular fluid. Inhibition of potassium currents by GABAB activation resulted in an excitatory effect on calyx terminal action potential firing. While in the control condition calyces could only fire a single action potential during step depolarizations, in the presence of baclofen they fired continuously during steps and a few even showed repetitive discharge. We also found a decrease in threshold for action potential generation and a decrease in first-spike latency during step depolarization. These results provide the first evidence for the presence of GABAB receptors on calyx terminals, showing that their activation results in an excitatory effect and that GABA inputs could be used to modulate calyx response properties.NEW & NOTEWORTHY Using in vitro whole cell patch-clamp recordings from calyx terminals in the vestibular end organs, we show that activation of GABAB receptors result in an excitatory effect, with decreased spike-frequency adaptation and shortened first-spike latencies. Our results suggest that these effects are mediated through inhibition of calcium-sensitive potassium channels.

Video Head Impulse Testing: From Bench to Bedside.

Over 30 years ago, the head impulse test (HIT) was measured with search coil recordings and it provided robust evidence for a new test of vestibular function that could detect impairment of a single semicircular canal, that is, the lateral canal. Over the next two decades, the diagnostic spectrum of HIT was expanded to the testing of vertical canals, differentiation of central from peripheral vestibulopathy, and incorporation of visual interaction-the suppressed head impulse. However, HIT measurement was limited to very few specialized laboratories that were able to maintain the time-consuming and expensive operation of the scleral search coil system, which is the gold standard in eye movement recording. The video HIT (vHIT) was validated for the first time over 10 years ago, against the search coils, and its introduction into dizzy clinics worldwide has revolutionized the practice of neuro-otology. Here we review the basic physiology, practical aspects, and clinical application of the vHIT.

Concepts and Physiological Aspects of the Otolith Organ in Relation to Electrical Stimulation.

BACKGROUND: This paper discusses some of the concepts and major physiological issues in developing a means of electrically stimulating the otolithic system, with the final goal being the electrical stimulation of the otoliths in human patients. It contrasts the challenges of electrical stimulation of the otolith organs as compared to stimulation of the semicircular canals. Electrical stimulation may consist of trains of short-duration pulses (e.g., 0.1 ms duration at 400 Hz) by selective electrodes on otolith maculae or otolithic afferents, or unselective maintained DC stimulation by large surface electrodes on the mastoids - surface galvanic stimulation. SUMMARY: Recent anatomical and physiological results are summarized in order to introduce some of the unique issues in electrical stimulation of the otoliths. The first challenge is that each otolithic macula contains receptors with opposite polarization (opposing preferred directions of stimulation), unlike the uniform polarization of receptors in each semicircular canal crista. The puzzle is that in response to the one linear acceleration in the one macula, some otolithic afferents have an increased activation whereas others have decreased activation. Key Messages: At the vestibular nucleus this opposite receptor hair cell polarization and consequent opposite afferent input allow enhanced response to the one linear acceleration, via a "push-pull" neural mechanism in a manner analogous to the enhancement of semicircular canal responses to angular acceleration. Within each otolithic macula there is not just one uniform otolithic neural input to the brain - there are very distinctly different channels of otolithic neural inputs transferring the neural data to the brainstem. As a simplification these channels are characterized as the sustained and transient systems. Afferents in each system have different responses to stimulus onset and maintained stimulation and likely different projections, and most importantly different thresholds for activation by electrical stimulation and different adaptation rates to maintained stimulation. The implications of these differences are considered.

The Superiority of the Otolith System.

BACKGROUND: The peripheral vestibular end organ is considered to consist of semi-circular canals (SCC) for detection of angular accelerations and the otoliths for detection of linear accelerations. However, otoliths being phylogenetically the oldest part of the vestibular sensory organs are involved in detection of all motions. SUMMARY: This study elaborates on this property of the otolith organ, as this concept can be of importance for the currently designed vestibular implant devices. Key Message: The analysis of the evolution of the inner ear and examination of clinical examples shows the robustness of the otolith system and inhibition capacity of the SCC. The otolith system must be considered superior to the SCC system as illustrated by evolution, clinical evidence, and physical principles.

Virtual signals of head rotation induce gravity-dependent inferences of linear acceleration.

KEY POINTS: Considerable debate exists regarding whether electrical vestibular stimuli encoded by vestibular afferents induce a net signal of linear acceleration, rotation or a combination of the two. This debate exists because an isolated signal of head rotation encoded by the vestibular afferents can cause perceptions of both linear and angular motion. We recorded participants' perceptions in different orientations relative to gravity and predicted their responses by modelling the effect of electrical vestibular stimuli on vestibular afferents and a current model of central vestibular processing. We show that, even if electrical vestibular stimuli are encoded as a net signal of head rotation, participants perceive both linear acceleration and rotation motions, provided the electrical stimulation-induced rotational vector has a component orthogonal to gravity. The emergence of a perception of linear acceleration from a single rotational input signal clarifies the origins of the neural mechanisms underlying electrical vestibular stimulation. ABSTRACT: Electrical vestibular stimulation (EVS) is an increasingly popular biomedical tool for generating sensations of virtual motion in humans, for which the mechanism of action is a topic of considerable debate. Contention surrounds whether the evoked vestibular afferent activity encodes a signal of net rotation and/or linear acceleration. Central processing of vestibular self-motion signals occurs through an internal representation of gravity that can lead to inferred linear accelerations in absence of a true inertial acceleration. Applying this model to virtual signals of rotation evoked by EVS, we predict that EVS will induce behaviours attributed to both angular and linear motion, depending on the head orientation relative to gravity. To demonstrate this, 18 subjects indicated their perceived motion during sinusoidal EVS when in one of four head/body positions orienting the gravitational vector parallel or orthogonal to the EVS rotation vector. During stimulation, participants selected one simulated movement from seven that corresponded best to what they perceived. Participants' responses in each orientation were predicted by a model combining the influence of EVS on vestibular afferents with known mechanisms of vestibular processing. When the EVS rotation vector had a component orthogonal to gravity, human perceptual responses were consistent with a non-zero central estimate of interaural or superior-inferior linear acceleration. The emergence of a perception of linear acceleration from a single rotational input signal clarifies the origins of the neural mechanisms underlying EVS, which has important implications for its use in human biomedical or sensory augmentation applications.

Models of vestibular semicircular canal afferent neuron firing activity.

Semicircular canal afferent neurons transmit information about head rotation to the brain. Mathematical models of how they do this have coevolved with concepts of how brains perceive the world. A 19th-century "camera" metaphor, in which sensory neurons project an image of the world captured by sense organs into the brain, gave way to a 20th-century view of sensory nerves as communication channels providing inputs to dynamical control systems. Now, in the 21st century, brains are being modeled as Bayesian observers who infer what is happening in the world given noisy, incomplete, and distorted sense data. The semicircular canals of the vestibular apparatus provide an experimentally accessible, low-dimensional system for developing and testing dynamical Bayesian generative models of sense data. In this review, we summarize advances in mathematical modeling of information transmission by semicircular canal afferent sensory neurons since the first such model was proposed nearly a century ago. Models of information transmission by vestibular afferent neurons may provide a foundation for developing realistic models of how brains perceive the world by inferring the causes of sense data.

Semicircular canal biomechanics in health and disease.

The semicircular canals are responsible for sensing angular head motion in three-dimensional space and for providing neural inputs to the central nervous system (CNS) essential for agile mobility, stable vision, and autonomic control of the cardiovascular and other gravity-sensitive systems. Sensation relies on fluid mechanics within the labyrinth to selectively convert angular head acceleration into sensory hair bundle displacements in each of three inner ear sensory organs. Canal afferent neurons encode the direction and time course of head movements over a broad range of movement frequencies and amplitudes. Disorders altering canal mechanics result in pathological inputs to the CNS, often leading to debilitating symptoms. Vestibular disorders and conditions with mechanical substrates include benign paroxysmal positional nystagmus, direction-changing positional nystagmus, alcohol positional nystagmus, caloric nystagmus, Tullio phenomena, and others. Here, the mechanics of angular motion transduction and how it contributes to neural encoding by the semicircular canals is reviewed in both health and disease.

Failure on the Foam Eyes Closed Test of Standing Balance Associated With Reduced Semicircular Canal Function in Healthy Older Adults.

OBJECTIVES: Standing on foam with eyes closed (FOEC) has been characterized as a measure of vestibular function; however, the relative contribution of vestibular function and proprioceptive function to the FOEC test has not been well described. In this study, the authors investigate the relationship between peripheral sensory systems (vestibular and proprioception) and performance on the FOEC test in a cohort of healthy adults. DESIGN: A total of 563 community-dwelling healthy adults (mean age, 72.7 [SD, 12.6] years; range, 27 to 93 years) participating in the Baltimore Longitudinal Study of Aging were tested. Proprioceptive threshold (PROP) was evaluated with passive motion detection at the right ankle. Vestibulo-ocular reflex (VOR) gain was measured using video head impulses. Otolith function was measured with cervical and ocular vestibular-evoked myogenic potentials. Participants stood on FOEC for 40 sec while wearing BalanSens (BioSensics, LLC, Watertown, MA) to quantify center of mass sway area. A mixed-model multiple logistic regression was used to examine the odds of passing the FOEC test based on PROP, VOR, cervical vestibular-evoked myogenic potential, and ocular vestibular-evoked myogenic potential function in a multisensory model while controlling for age and gender. RESULTS: The odds of passing the FOEC test decreased by 15% (p < 0.001) for each year of increasing age and by 8% with every 0.1 reduction in VOR gain (p = 0.025). Neither PROP nor otolith function was significantly associated with passing the FOEC test. CONCLUSIONS: Failure to maintain balance during FOEC may serve as a proxy for rotational vestibular contributions to postural control. Semicircular canals are more sensitive to low-frequency motion than otoliths that may explain these relationships because standing sway is dominated by lower frequencies. Lower VOR gain and increased age independently decreased the odds of passing the test.