Traditional and Non-Traditional Inputs to the Vestibular System

One of the primary functions of the vestibular system is to provide stabilizing reflexes to the eye, head, and body. These reflexes are often coordinated with inputs from the visual and proprioceptive systems. More recently, research has shown that other, non-traditional, stimuli also affect the vestibular system, though the scope of this research has been limited. This thesis explores the effect of both traditional and non-traditional inputs on the vestibular system by characterizing their influence compensatory movements. We begin by looking at the influence of the vestibular periphery and efference copy on compensatory eye movements (Chapter 2). While each of these has been described individually (as the vestibular-ocular reflex (VOR) and pre-programmed eye movements (PPEM) respectively), there is currently controversy in the field regarding 1) to what extent PPEM influence gaze stabilization in healthy animals, and 2) how these two inputs interact with each other. We propose a model of gaze stability in which VOR and PPEM work cooperatively, and compare model predictions to our data as well as data others have reported. We found that our model accurately predicted eye movements for all behavioral contexts tested. In Chapter 3, we describe the effect of single high-intensity noise exposure on the vestibular system. Currently, controversy surrounds whether, and to what extent, noise damages the semi-circular canals. We characterized changes to both ocular and head stability to better answer this question and found that after noise exposure there was loss of both ocular and head stability. However, the exact nature of this deficit was not as expected and the influence of cervical pathways after vestibular lesion is discussed. Finally, in Chapter 4, we examine the effect of galvanic vestibular stimulation (GVS) and optokinetic stimulation on standing posture. We propose a model of postural stability inspired by the velocity storage model of ocular stability. While others have proposed more complex models that make similar predictions, those predictions have not been explicitly tested and, further, it’s not clear if the added complexity is necessary. We found that, while simple, our model could correctly predict subjects’ responses to both stimuli, suggesting that the body interprets and uses sensory information for postural stability in a manner similar to that for ocular stability. Taken together these findings demonstrate that the influence of non-traditional inputs and pathways to vestibular system is substantial and should be considered both in laboratory and clinical settings. Specifically, we showed in Chapter 2 that PPEM are not merely an enhanced or adapted VOR, but part of a unique gaze stabilization system that merits independent consideration. In Chapter 3, we showed that a single noise exposure can cause significant functional damage to the vestibular system, suggesting that patients with noise-induced hearing loss should be tested for vestibular loss as well. Finally, in Chapter 4, we showed that GVS can be integrated like natural vestibular stimulation but only if it is properly conditioned first. This is of particular importance for vestibular prosthetic design, which uses GVS to substitute for lost vestibular input.PHDBiomedical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/143914/1/hastepha_1.pd

Evidence for a reference frame transformation of vestibular contributions to voluntary reaching movements

Les estimations des mouvements de soi provenant des signaux vestibulaires contribuent à la planification et l’exécution des mouvements volontaires du bras lorsque le corps se déplace. Cependant, comme les senseurs vestibulaires sont fixés à la tête alors que le bras est fixé au corps, les signaux vestibulaires doivent être transformés d’un système de référence centré sur la tête à un système centré sur le corps pour pouvoir contribuer de façon appropriée au contrôle moteur du bras. Le but premier de ce travail était d’étudier l’évidence d’une telle transformation. La stimulation galvanique vestibulaire (SGV) a été utilisée pour activer les afférences vestibulaires et simuler une rotation autour d’un axe naso-occipital fixe pendant que des sujets humains faisaient des mouvements du bras dans le plan horizontal, avec la tête dans différentes orientations. Une transformation des signaux vestibulaires implique que la SVG devrait simuler une rotation autour d’un axe horizontal lorsque la tête est droite et autour d’un axe vertical lorsque la tête est en flexion antérieure. La SGV devrait ainsi perturber les mouvements du bras en fonction de l’orientation de la tête. Nos résultats démontrent que les signaux vestibulaires contribuant aux mouvements d’atteinte sont effectivement transformés en un système de référence centrée sur le corps. Le deuxième but de ce travail était d’explorer les mécanismes utilisant ces signaux vestibulaires transformés. En comparant les effets de la SGV appliquée avant ou pendant les mouvements d’atteinte nous avons montré que les signaux vestibulaires transformés contribuent à des mécanismes de compensation distincts durant la planification des mouvements d’atteinte comparativement à l’exécution.Vestibular signals provide self-motion estimates that contribute to the planning and execution of voluntary reaching movements during body motion. However, because the vestibular sensors are fixed in the head whereas the arm is fixed to the trunk vestibular signals must be transformed from a head-centered to a body-centered reference frame to contribute appropriately to limb motor control. The first goal of the current work was to investigate the evidence for such a transformation. To do so we used galvanic vestibular stimulation (GVS) to selectively activate vestibular afferents and simulate rotation about a fixed roughly naso-occipital axis as human subjects performed reaching movements with the head in different orientations. If vestibular signals that contribute to reaching are transformed to body-centered coordinates, then with the head upright GVS should simulate mainly tilt about an earth-horizontal axis (roll), whereas with the head pitched forward the same stimulus should simulate rotation about an earth-vertical axis (yaw). We therefore predicted that GVS should perturb horizontal-plane reach trajectories in a head-orientation dependent manner. Our results demonstrate that vestibular signals which contribute to reaching are indeed transformed to a body-centered reference frame. The second goal of this work was to explore the mechanisms that use these transformed vestibular signals. By comparing the effect of GVS applied during versus prior to reaching we also provide evidence that transformed vestibular signals contribute to distinct compensation mechanisms for body motion during reach planning versus execution

Behavioural manipulations of parietal lobe function

The aim of this thesis was to develop a novel behavioural technique to disrupt parietal function in order to induce top-down cortical modulation of low-level brain structures, namely the brainstem mediated vestibulo- ocular reflex and the early visual cortex. The premise of the technique was based upon using stimuli that engaged overlapping neuronal networks. To this end, we employed a technique that involved concurrent vestibular activation and viewing of bistable perceptual visual stimuli or performing visualised spatial attention tasks. The thesis presents data that shows the ability of this technique to induce a handedness related cortical modulation of the vestibulo-ocular reflex and modulation of the early visual cortex. Subsequently we applied trans-cranial direct stimulation to directly disrupt parietal inter-hemispheric balance in order to induce an asymmetrical modulation of the VOR and propose a revised computational model for vestibular processing. The results from these experiments present the first behavioural demonstration that vestibular cortical processing is strongly lateralised to the non-dominant hemisphere. We propose that this technique developed and validated in this thesis can be used to further probe and investigate cognitive parietal function such as numerical cognition and human decision making.Open Acces

Multimodal cue integration in balance and spatial orientation

The global objective of this thesis was to make a significant contribution to our understanding of how the human brain integrates multisensory, multimodal information to inform our motion through space. The primary objectives were to discern whether visual system differentially encodes visual motion coherence and how both allocentric visual cues interact with vestibular system to tell us where and when we are in physical space. A secondary objective was to develop current techniques for the recording and analysis of visuo-vestibular sensory information for the purpose of multisensory, multimodal integration. I studied the response of cortical visual motion area V5/MT+ to random dot kinematograms (RDK) of varying motion coherence, from complete coherence to random. I used the probability of observing TMS (transcranial magnetic stimulation) evoked phosphenes before and after the RDK as a measure of cortical excitability change. I could not show what I had hypothesised: that coherent and random motion elicited a similar net effect upon V5/MT+ excitability, with intermediary coherences of motion having comparatively less effect. However, I argue that a large factor was insufficient sample size to find the effects given the analyses used. The results do show trends consistent with coherent and random net effects being achieved by different modes of cortical activation, and the study will inform future investigation with the paradigm used. I also measured cortical excitability change at a range of relative TMS intensities. This elicited a significant differential effect consistent with the theory that TMS facilitates neurons as a function of the amount of signal they carry. In a separate TMS evoked phosphene study, I show an interaction between whole body rotation in yaw and the ability to observe phosphenes in V5/MT+; as a function of the TMS intensity used and the velocity of whole body rotation used, relative to perceptual thresholds. As I found no main effects, I could not show whether the findings were consistent with a model of reciprocal visual and vestibular cortical inhibition. My work can be considered a feasibility study to inform further investigation. I also used a visual-vestibular mismatch paradigm to probe how erroneous visual landmark cues update veridical vestibular estimates of angular position and motion duration. I used visual masking to reduce the reliability of the visual landmark cues, prevent visual capture and to also elicit subliminal encodement. I found that reversion to vestibular estimates of angular position was made as a function of the noise inherent in the masked visual landmark cues. I found that it was possible to subliminally encode visual landmarks to update vestibularly derived estimates of motion duration. Lastly, I investigated the combination of a two-interval forced choice technique to record estimates of vestibularly derived angular position and a Bayesian Inference technique to parameterize the characteristics of the angular position estimates. I show this combination provides accurate estimates at the subject level and is suitable for incorporation in a Bayesian inference model of multimodal integration. The hypothesis I aim to test in the future is that if visual landmark and vestibular cues of angular position operate within different spatial reference frames, they cannot be optimally integrated in the brain analogous to a Bayesian Inference model of the multimodal integration.Open Acces

Investigating the interplay of the human attentional and vestibular systems using transcranial magnetic stimulation

The aim of this doctoral thesis was to investigate the relationship between the processing of vestibular information, on the one hand, and higher cognitive functions such as visual (spatial) attention and perceptual decision making, on the other. In order to draw causal inference about the role of specific cortical regions in this interplay, two experimental studies were conducted which combined psychophysical task designs using verticality judgment tasks with transcranial magnetic stimulation (TMS). The first study employed a simultaneous TMS-EEG approach to examine the role of the right intraparietal sulcus (IPS) within the dorsal parietal cortex in verticality judgments – a cortical area that has repeatedly been associated with both the visual attention and vestibular systems. Facilitatory effects of right IPS TMS on the bias of verticality perception were reported and mirrored by EEG results, which pointed to a normalization of individual perceptual biases reflected in a fronto-central ERP component following the stimulation. In contrast, no effects of left IPS TMS on either behavioural or electrophysiological measures were observed and right IPS TMS did not modulate performance in a control task that used the same set of stimuli (vertical Landmark task). These findings point to a causal role of the right IPS in the neuronal implementation of upright perception and strengthen the notion of vestibular-attentional coupling. In the second study verticality judgments had to be made under different levels of perceptual demand to address the question of how perceptual decision making interacts with vestibular processing. Stimuli adapted from those used in the first study were presented in a visual search setting, which required perceptual and response switches, in a way that varied attentional demands. This task was combined with offline theta-burst TMS applied to the dorsal medial frontal cortex (dMFC). The dMFC has been found to crucially contribute to perceptual decision making and is connected to core parts of the vestibular cortical network. Analysis of distinct features of behavioural performance before as compared to following dMFC TMS revealed a specific involvement of the dMFC in establishing the precision and accuracy of verticality judgments, particularly under conditions of high perceptual load. In summary, the results of the two studies support the idea of a functional link between the processing of vestibular information, (spatial) attention, and perceptual decision making, giving rise to higher vestibular cognition. Moreover, they suggest that on a cortical level this interplay is achieved within a network of multimodal processing regions such as the parietal and frontal cortices

Central Adaptation after Peripheral Vestibular Injury

This thesis examines how the human brain adapts after peripheral vestibular injury. Vestibular perceptual function is used as a probe of cortical vestibular function. A paradigm determining vestibular perceptual thresholds to yaw axis rotation by a method of limits is described. Asymmetry in the thresholds is induced in normal subjects with galvanic vestibular stimulation. In patients with acute vestibular neuritis, perceptual thresholds were bilaterally elevated, with less asymmetry when compared to the brainstem reflexive function. Thresholds were measured in a prospective longitudinal study in vestibular neuritis patients, assessed acutely and at follow-­‐up (n=16). Assessments comprised vestibular caloric testing, visual dependency measures, questionnaire measures of symptom load, anxiety, depression and fear of body sensations. Clinical recruitment found a low rate of correct diagnoses by referring clinicians. Symptomatic outcome at follow-up was associated with increased visual dependence, asymmetric caloric function, increased anxiety and depression. It was also associated with increased fear and anxiety of body sensations present acutely, suggesting this may be predisposing. The anatomical substrate of central compensation was investigated in patients with bilateral vestibular failure (n=12) and normal controls (n=15) using functional MRI. A novel air turbine-powered vibrating device was developed to provide high and low levels of proprioceptive stimulus to neck rotator muscles. This was combined with a horizontal visual motion paradigm in a factorial design. A lateralised interaction was found in the lateral occipital visual processing areas in the avestibular patients. In addition to the known visual-vestibular interaction, this demonstrates a visuo-proprioceptive interaction, which may reflect compensation after vestibular injury. Conclusions: Vestibular perceptual function can be measured in disease, and is elevated in patients with acute peripheral vestibulopathy. Specific psychological and physiological factors associated with clinical recovery after vestibular neuritis are proposed. Functional MRI shows that proprioceptive signals interact with visual motion signals in patients with vestibular failure

Implementation of a Central Sensorimotor Integration Test for Characterization of Human Balance Control During Stance

Balance during stance is regulated by active control mechanisms that continuously estimate body motion, via a “sensory integration” mechanism, and generate corrective actions, via a “sensory-to-motor transformation” mechanism. The balance control system can be modeled as a closed-loop feedback control system for which appropriate system identification methods are available to separately quantify the sensory integration and sensory-to-motor components of the system. A detailed, functionally meaningful characterization of balance control mechanisms has potential to improve clinical assessment and to provide useful tools for answering clinical research questions. However, many researchers and clinicians do not have the background to develop systems and methods appropriate for performing identification of balance control mechanisms. The purpose of this report is to provide detailed information on how to perform what we refer to as “central sensorimotor integration” (CSMI) tests on a commercially available balance test device (SMART EquiTest CRS, Natus Medical Inc, Seattle WA) and then to appropriately analyze and interpret results obtained from these tests. We describe methods to (1) generate pseudorandom stimuli that apply cyclically-repeated rotations of the stance surface and/or visual surround (2) measure and calibrate center-of-mass (CoM) body sway, (3) calculate frequency response functions (FRFs) that quantify the dynamic characteristics of stimulus-evoked CoM sway, (4) estimate balance control parameters that quantify sensory integration by measuring the relative contribution of different sensory systems to balance control (i.e., sensory weights), and (5) estimate balance control parameters that quantify sensory-to-motor transformation properties (i.e., feedback time delay and neural controller stiffness and damping parameters). Additionally, we present CSMI test results from 40 subjects (age range 21–59 years) with normal sensory function, 2 subjects with results illustrating deviations from normal balance function, and we summarize results from previous studies in subjects with vestibular deficits. A bootstrap analysis was used to characterize confidence limits on parameters from CSMI tests and to determine how test duration affected the confidence with which parameters can be measured. Finally, example results are presented that illustrate how various sensory and central balance deficits are revealed by CSMI testing

Psychophysical and Psychological Factors Affecting Recovery from Acute Balance Disorders

Patients with acute vestibular neuritis are traditionally investigated with caloric or rotational examination of the vestibular-ocular reflex. However, clinical outcome is poorly predicted by such vestibular reflex assessments. We hypothesised that symptomatic recovery would depend upon higher order visuo-vestibular compensatory mechanisms. Thirty-one patients were studied in the acute and recovery phases of vestibular neuritis (median 2 days and 10 weeks, respectively). Patients underwent examination of vestibulo-ocular and vestibular-perceptual responses, at threshold and supra-threshold levels. Supra-threshold stimuli (90°/s velocity step rotations) allowed quantification of vestibulo-ocular and vestibulo-perceptual time constants. Additional measures of visual dependency (rod-and-disc task), dizziness symptom load (Vertigo Symptom Scale and Dizziness Handicap Inventory) and psychological factors (including - autonomic arousal, anxiety, depression, fear of bodily sensations) were obtained. Vestibulo-perceptual and vestibulo-ocular thresholds were raised and asymmetric acutely and remained slightly elevated and asymmetric at recovery. Acutely, supra-threshold vestibulo-ocular time constants were shortened and asymmetric. In contrast, perceptual responses were reduced but notably symmetrical. At recovery, vestibulo-ocular supra-threshold responses remained abnormal but perceptual supra-threshold responses normalised. Visual dependency was significantly elevated above normals in both acute and recovery stages. Vertigo symptom recovery was significantly predicted by acute levels of visual dependency (p=0.002), autonomic anxiety (p=0.004). A number of measures were associated with vertigo symptoms at recovery, in addition to visual dependency (p=0.012) and autonomic anxiety (p<0.001), including - anxiety and depression (p<0.003), fear of body sensations (p=0.033), vestibular perceptual thresholds (p=0.017) and caloric canal paresis (p=0.001). Factor Analysis revealed a strong association between clinical outcome, visual dependency and psychological factors, all loading on a single component accounting for 59.15% of the variance. The bilateral suppression of supra-threshold vestibular perception observed acutely represents a hitherto unrecognised central adaptive ‘anti-vertiginous’ mechanism. However, poor symptomatic recovery is best predicted by increased visual dependency and psychological factors. The findings show that long term recovery from unilateral vestibular deficit is mediated by central compensatory mechanisms, including multi-sensory integration and psychological processing

Sensorimotor postural control in healthy and pathological stance and gait

Postural control during standing and walking is an inherently unstable task requiring the interaction of various biomechanical, sensory, and neurophysiological mechanisms to shape stable patterns of whole-body coordination that are able to counteract postural disequilibrium. This thesis focused on the examination of central aspects of the functional roles of these mechanisms and the modes of interaction between them. A further aim was to determine the conditions of dynamic stability for healthy standing and walking performance as well as for certain balance and gait disorders. By studying movement fluctuations in the walking pattern it could be demonstrated that dynamic stability during walking depends on gait speed and is differentially regulated for the medio-lateral and the fore-aft walking planes. Stability control in the fore-aft walking plane exhibits attractor dynamics typical for a dynamical system. Accordingly, the most stable pattern of movement coordination in terms of minimal fluctuations in the order parameter (i.e., the relative phase between the two oscillating legs) can be observed at the attractor of self-paced walking. Critical fluctuations occur at increasingly non-preferred speeds, indicating a loss of dynamic gait stability close to the speed boundaries of the walking mode. Moreover, stability control during slow walking is critically dependent on sensory feedback control, whereas dynamic stability during fast walking relies mainly on the smooth operation of cerebellar pacemaker regions. Disturbances of sensory and cerebellar locomotor control in certain gait disorders could be further linked to a loss of dynamic gait stability, in particular an increased risk of falls. Furthermore, this thesis examined alterations in the sensorimotor postural control scheme that may trigger the experience of subjective imbalance and vertigo in the conditions of phobic postural vertigo and visual height intolerance. Both conditions are characterized by an inadequate mode of balance regulation featuring increased levels of open-loop balance control and a precipitate integration of closed-loop sensory feedback into the postural control scheme. This inadequate balance control strategy is accompanied by a stiffening of the anti-gravity musculature and is elicited by specific influences of attention and sensory feedback control. The findings of this thesis contribute to the understanding of central sensorimotor mechanisms involved in the control of dynamic postural stability during standing and walking. They further provide relevant information for the differential diagnosis and fall risk estimation of certain balance and gait disorders