Vestibular Implants Tested in Human Subjects

The goal of this study is to improve the vestibular implant's ability to reduce the vestibular-dependent perceptual, postural, and visual symptoms that affect patients with severe peripheral vestibular damage. The long-term research plan is focused on exploring the three questions which must be answered to assess the clinical utility of a vestibular implant (VI) in vestibulopathic patients - i) how can information transfer from the VI sensors to the brain be optimized; ii) how does the three-dimensional angular velocity information provided by the VI interact in the brain with other sensorimotor (vision, otolith, efferent) signals; and iii) how effectively does the VI alleviate the behavioral deficits and subjective symptoms experienced by patients with severe vestibular damage. The current study will be used to focus on two key subsets of these questions. Over one year, the investigators will study approximately 5 patients who have severe bilateral vestibular damage and functioning VI's, which will focus on aim 1: how the angular velocity information sensed by the VI can be optimally transferred to the brain; and aim 2: how effectively the VI improves the clinical status of vestibulopathic patients when they receive acute and sub-acute (3 days) motion-modulated stimulation. In sum, the investigators aim to improve the efficacy of the VI in human subjects by developing new knowledge about how the brain processes motion cues provided by the VI and correlating this information with behavioral outcomes.

Aim1: Optimizing information transfer from the VI to the brain: the investigators will study two approaches - altering the transfer function that relates the head's angular velocity to the electrical stimulation applied by the VI to the canal ampullary nerves; and utilizing the VI's unique capability to add noise to vestibular afferents. Regarding the former, the study team plans to initiate investigation of the principal components of the transfer function by testing the VI's capabilities when - the baseline resting stimulation rate is modified up or down; the temporal filtering (e.g., corner frequency of the high-pass filter) of the angular velocity signal recorded by the rate sensor is modified; the slope of the linear component of the hyperbolic tangent function that relates filtered head velocity to stimulation strength is altered; and different modes of stimulation modulation are used to encode head velocity (e.g, modifying the amplitude, the rate, or co-modulating the amplitude and rate of the current pulses). Regarding the use of noise, the investigators will test a given transfer function with different amplitudes of broad-band white electrical noise superimposed on the stimulation that encodes angular velocity, to determine if information transfer can be improved from the VI to the brain with low-level noise via stochastic resonance, as has been demonstrated in other sensory systems. To determine the efficacy of these approaches, the study team will measure the three basic vestibular-mediated behaviors (eye movements, posture, and perception). In particular we will focus on the amplitude and threshold of the angular vestibulo-ocular reflex (VOR), yaw-axis perceptual thresholds, and postural sway thresholds and amplitude, with the goal of defining the transfer function and noise level that minimizes thresholds (e.g., optimizes the signal-to-noise ratio) and maximizes the amplitude of the behavioral responses. One corollary of these studies is to examine if the different behavioral pathways are optimized with different stimulus parameters, as is suggested by the preliminary data. Aim 2: Characterizing the effects of VI stimulation on clinical status: Vestibular-mediated behaviors are crucial to patient wellbeing and are degraded after severe vestibular damage. The investigators will initiate the assessment of the VI's clinical utility by quantifying the VOR, posture/gait, and perception using paradigms that isolate the VI's contributions to these behaviors (e.g., VOR during yaw-axis rotation) or paradigms that recapitulate normal activities such as self-generated walking, which require the brain to synthesize the angular velocity information provided by the VI with other sensorimotor cues. The investigators will study these vestibulopathic patients before the VI is activated ('pre'), one hour after activation ('acute,' which allows participants adequate time to adapt to the tonic VI stimulation), and then daily for three days while motion-modulated stimulation is provided by the VI during normal activities ('chronic'). The investigators will also have participants complete several questionnaires prior to stimulation and again in the acute and chronic stimulation states to quantify their subjective responses to VI stimulation. These will include questionnaires that characterize the severity of subjective dizziness and imbalance (Dizziness Handicap Inventory \[DHI\], Activities Specific Balance Confidence Scale \[ABC\]); oscillopsia (the Oscillopsia Functional Impact Scale); and a more general quality of life measurement (the Short Form-36 Health Survey). These questionnaires will be modified so they reflect current levels of symptomatology, since the study team will be capturing changes over a short time-frame. The investigators expect that behavior and symptoms will improve during the period of motion-modulated stimulation such that measurements and subjective reports in the 'chronic' stimulation state will be closer to normal than during the 'acute' or 'pre' stimulation states. More complex behaviors (e.g. balance while walking, ABC scores) are predicted to improve more slowly than behaviors that rely on isolated angular velocity cues (e.g., yaw axis VOR, oscillopsia scores). In sum, this study will provide a solid foundation to build upon for future research in which the investigators will further examine the clinical utility of the VI.