Vestibular Implants Tested in Human Subjects
Condition: Vestibular Disorder; Vestibular Ataxia; Vestibular Loss, Bilateral
MeSH terms: Vestibular Diseases; Bilateral Vestibulopathy
Study type: Interventional

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Vestibular prosthesis/implant; Vestibular Implant Stimulation
Intervention type(s): Device; Device
Intervention description(s): The intervention is a vestibular prosthesis which our collaborators at the University of Geneva are implanting into the inner ear in deaf patients without vestibular function who are receiving a cochlear implant. The vestibular implant (VI) has three rate sensors and senses angular head velocity in three dimensions and provides this information to the brain by stimulation the afferent nerves innervating the three semicircular canals. Our goal is to use the VI to better understand how the brain processes this prosthetic information and uses it to generate meaningful behavioral responses including eye movements, postural control, and perception.; VI subjects will be studied before the implant is activated (pre) and then after it is turned on (acute On); this will take about 2 hrs. Then they will have 8 hours of motion-modulated VI stimulation while they actively explore the hospital environment, after studies will be repeated (chronic On). Each set of outcome experiments will be performed twice, once with and once without low-levels of stochastic noise added to the VI stimulation provided for the 8-hour period. The noise amplitude is tailored to each patient to maximize stochastic resonance so extraction & integration of spatial signal provided by the VI will always be the first experiment, but the order of the subsequent outcome sessions (active/passive head rotations, tilt/translation motion discrimination and VOR behavioral changes & postural control) will be randomized. VI subjects will participate in 4 full-day sessions, each separated by at least a month.
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: eye movements; perception; vestibular; dizziness; sensory integration; prosthesis