Subthreshold Vestibular Stimulation as a Strategy for Rehabilitation

Overview

The nervous system responds to changes in external or internal conditions by altering the behavior of neurons through multiple forms of neural plasticity. A specific form of plasticity, "homeostatic plasticity", stabilizes neural activity by driving the excitability of neurons toward a "set-point" level of activity. Over the last six years, new data have come to light showing that the vestibular system also possess a robust capacity to modulate sensitivity to self-motion cues in response to prolonged periods of motion. Collectively, these studies have demonstrated a capacity to use motion perturbations (i.e., low, or high levels of vestibular stimulation) to dynamically adjust the sensitivity of the vestibular system on both the single neuron and behavioral levels. The ability to use subthreshold motion stimuli to drive plasticity in the vestibular system motivates this study. The investigators aim to determine the impact of subthreshold motion on (a) balance performance and (b) balance training in individuals with peripheral vestibular hypofunction.

Detailed description

The investigators aim to test (1) if sub threshold motion improves motion perception, (2) if sub threshold motion improves balance performance, and (3) if sub threshold motion prior to balance training leads to improved balance performance. Twenty-four subjects with peripheral vestibular hypofunction (12 with bilateral and 12 with unilateral hypofunction) and twenty-four healthy control participants will complete the study. Each participant will complete four visits to the laboratory. Day 1 will measure the capacity to modify balance and self-motion perception after a single block of subthreshold motion, including any retention effects after a washout period. Days 2-4 will be performed in random order and will test changes in balance and self-motion perception after (a) repeated balance training, (b) repeated subthreshold motion, and (c) balance training combined with sub threshold motion.

Interventions

• Behavioral Subthreshold Vestibular Conditioning
  Subthreshold vestibular conditioning will be performed while seated on a motion platform and blindfolded. The stimulus will consist of a pseudorandom sum-of-sinusoids roll tilt motion (\~0.08 to 1 Hz) delivered at a peak velocity equal to 57.4% of the measured baseline roll tilt perceptual threshold (e.g., 0.574°/s for a 1 °/s threshold). The participant will be informed that while the chair may vibrate or move slightly, the motion will not occur in any particular direction.
• Behavioral Balance Training
  Balance training will consist of progressive exposure to continuous one-dimensional roll pseudorandom platform perturbations delivered using a 6DoF motion platform. Participants will stand on a MOOG hexapod motion platform and will be secured using a safety harness tethered to the ceiling and a full enclosure of safety rails. Roll tilt perturbations will be progressed by gradually increasing the displacement/velocity/acceleration of the platform motion.
• Other Balance Training Plus Subthreshold Conditioning
  Subthreshold vestibular conditioning will be performed while seated on a motion platform and blindfolded prior to each bout of balance training. Subthreshold conditioning will consist of a pseudorandom sum-of-sinusoids roll tilt motion (\~0.08 to 1 Hz) delivered at a peak velocity equal to 57.4% of the measured baseline roll tilt perceptual threshold (e.g., 0.574°/s for a 1 °/s threshold). The participant will be informed that while the chair may vibrate or move slightly, the motion will not occ

Primary outcome measures

• Perturbed Stance Postural Control [Time frame: At each of the 4 visits, outcome measures will be captured at (1) beginning of the visit (i.e., baseline), (2) post-intervention (20 minutes after baseline), and (3) post-washout (20 minutes after the post-intervention assessment).]
• Vestibular Perceptual Thresholds - 0.5Hz Roll Tilt [Time frame: At each of the 4 visits, outcome measures will be captured at (1) beginning of the visit (i.e., baseline), (2) post-intervention (20 minutes after baseline), and (3) post-washout (20 minutes after the post-intervention assessment).]

Eligibility criteria

Inclusion Criteria for Bilateral Vestibular Hypofunction:

1\. Bilateral lateral canal VOR gain of < 0.8 on video head impulse testing OR bilateral positive bedside head impulse test

Inclusion Criteria for Unilateral Vestibular Hypofunction:

1\. Unilateral yaw aVOR gain of < 0.8 on video head impulse testing OR unilateral positive bedside head impulse test

Inclusion Criteria for all Participants:

• Must be able to stand for 5 minutes unassisted
• No leg or foot amputations
• No lower limb braces
• Not currently pregnant by self-report
• Weight <= 300 pounds (due to limitations of testing equipment)

Exclusion Criteria for all participants:

• Severe head trauma or traumatic brain injury
• History of seizures
• Alternative neurologic illness or condition known to impact vestibular or balance function (e.g., stroke, neurodegenerative disorders, demyelinating illness)
• Major psychiatric (e.g., panic disorder, psychosis, etc.) disorder
• Any of the following eye diseases or conditions: amblyopia (or "lazy eye") or history of amblyopia, diagnosis of age- related macular degeneration, retina dystrophy, glaucoma, cataracts,
• Recent (<6 months) orthopedic injury that may affect test performance
• Recent surgery (< 6 months) that may impact test performance.
• Other severe health problems (heart disease, pulmonary disease, cancer, etc.) that may affect test performance
• Due to potentially nauseogenic nature of some motions and to protect fetus and mother, pregnant women will also be excluded from this study

• Since the investigators cannot address every possible potential individual recruit in advance, additional exclusion criteria may be required.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Basic science

Study locations

United States · 1 center

• Creighton University — Omaha

Publications

• Wagner AR, Kobel MJ, Tajino J, Merfeld DM. Improving self-motion perception and balance through roll tilt perceptual training. J Neurophysiol. 2022 Sep 1;128(3):619-633. doi: 10.1152/jn.00092.2022. Epub 2022 Jul 27. PMID 35894439
• Dietrich H, Straka H. Prolonged vestibular stimulation induces homeostatic plasticity of the vestibulo-ocular reflex in larval Xenopus laevis. Eur J Neurosci. 2016 Jul;44(1):1787-96. doi: 10.1111/ejn.13269. Epub 2016 Jun 1. PMID 27152983
• Kobel MJ, Wagner AR, Merfeld DM, Mattingly JK. Vestibular Thresholds: A Review of Advances and Challenges in Clinical Applications. Front Neurol. 2021 Feb 19;12:643634. doi: 10.3389/fneur.2021.643634. eCollection 2021. PMID 33679594

Identifiers

NCT: NCT06732440 · 2004550 · 4R00DC020759-02

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗