Back to results

Analysis of Vestibular Compensation Following Clinical Intervention for Vestibular Schwannoma

Primary Purpose

Migraine, Vestibular Migraine, Vestibular Schwannoma

Status

Enrolling by invitation

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Temporal Binding Adaptation - TBW training

Temporal Binding Adaptation - PSS training

Temporal Binding Adaptation - PSS adaptation with VI stimulation

Chronic Motion-modulated Stimulation

About this trial

This is an interventional basic science trial for Migraine focused on measuring sensory integration, cochlear implant, vestibular implant, balance, dizziness, vestibular disorders

Eligibility Criteria

8 Years - 80 Years (Child, Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Normal subjects

normal vestibular-oculomotor exams
normal low-frequency standard rotational testing
normal hearing

Migraine

meets International Headache Society (IHS) criteria for migraine with or without aura
tested more than 2 weeks after most recent migraine headache

Vestibular Migraine

meets Barany Society criteria for vestibular migraine, which includes:
episodic vestibular symptoms that occur with headaches that meet the IHS criteria for migraine
tested more than 2 weeks after most recent migraine headache or vestibular episode

Vestibular Schwannoma

existence of unilateral vestibular schwannoma (pre & post surgical resection)
must have sub-occipital surgical approach with complete sectioning of the vestibular nerve
rotational testing to assess pre-surgical vestibular function
audiogram
brain MRI consistent with vestibular schwannoma
audiography in each ear

Vestibular (VI) and Cochlear (CI) Implant subjects

scheduled for CI surgery because of deafness
minimum 5 year history of documented absence of auditory and vestibular function, based on review of their audiograms and vestibular tests
specific vestibular criteria: peak ice water caloric response of less than 3deg/s for each ear; yaw VOR time constant <3s and gain <0.25; and reduced head impulse gain (<0.25) for all canal planes
specific audiographic criteria: 80dB or greater sensorineural hearing loss in both ears

Exclusion Criteria:

Normal subjects

history of otologic or neurologic disease
on vestibular suppressant medication (benzodiazepine, antihistamine, anticholinergic)

Migraine

history of vestibular symptoms (other than motion sickness)
evidence of other neurologic or otologic dysfunction
on migraine prophylactic medications
on vestibular suppressant medication (benzodiazepine, antihistamine, anticholinergic)

Vestibular Migraine (VM)

other neurologic or otologic dysfunction as defined above except for central eye movement findings that are consistent with VM and therefore not exclusionary.
on migraine prophylactic medication
on vestibular suppressant medication (benzodiazepine, antihistamine, anticholinergic)

Vestibular Schwannoma

other otologic disease (other than presbycusis) or any neurologic disease (other than migraine)
NF2
on vestibular suppressant medication (benzodiazepine, antihistamine, anticholinergic)

Sites / Locations

Massachusetts Eye and Ear Infirmary

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Arm Label

Normal Controls

Central Vestibular Dysfunction

Peripheral Vestibular Dysfunction

Implant Subjects

Arm Description

normal control subjects - no history of neurologic or inner ear disease The investigators will characterize vestibular spatial and temporal precision by calculating perceptual thresholds and reaction times for vestibular (yaw rotation, ytranslation) stimuli in normal subjects over a wide age range. Vestibular-visual temporal binding is then performed on each subject and the relationship between the principal parameters (vestibular perceptual thresholds [inversely related to spatial precision], vestibular reaction time variability [inverse of temporal precision], and the PSS and TBW from the temporal binding paradigm) will be examined. The investigators will collect qualitative assessments of dizziness/disbalance (DHI: dizziness handicap index) and quantitative measurements of balance and vestibular function (FGA: functional gait analysis, postural sway, and standard rotational testing - VOR gain, time constant, asymmetry).

Migraine and Vestibular Migraine patients The investigators intend to evaluate vestibular (yaw rotation or y-translation) - visual temporal binding in people with a wide range of motion sickness sensitivities (as quantified with standard questionnaires), including normal subjects, people with migraine and with vestibular migraine. The investigators will use our standard adaption method to narrow the TBW in these subjects, and will also employ PSS adaptation if a consistent pattern emerges that relates MS sensitivity to the PSS. The investigators will induce motion sickness using a pseudo-Coriolis task (so susceptibility can be quantified pre and post training).

Vestibular Schwannoma patients The basic approach is to characterize the precision of their vestibular information (perceptual thresholds for spatial precision, reaction times for temporal precision), and their temporal binding characteristics for vestibular (yaw rotation or y-translation)-visual inputs, in three states: pre-op, sub-acute post-op (2-6 weeks), and chronic post-op (6 months+). At each state the investigators will also assess the quality of their vestibular-mediated behaviors through questionnaires (e.g. DHI), postural sway, functional gait analysis, and standard rotational testing (VOR gain, time constant, and asymmetry).

Cochlear Implant (CI)/Vestibular Implant (VI) patients A causative role for vestibular precision in temporal binding will be investigated in the VI patients, since the noise characteristics of the vestibular channel will be varied and to determine how this affects thresholds and temporal binding. As part of a second aim, the investigators will use VI and CI prosthetic signals in patients who have never received them together to see how the brain process sensory cues to which it is essentially naïve. Finally, after the acute experiments the investigators will provide 8 hours of 'physiologic' VI and CI stimulation by turning both implants on, sound modulates activity in the CI as usual, and angular head motion modulates activity in the VI while the subject actively explores the hospital environment.

Outcomes

Primary Outcome Measures

Changes in postural sway/balance

Measurements of postural sway during Romberg testing on floor and foam (including an extra 60s balance test during which subject stands on foam and shakes head left and right at 1hz frequency while fixating on a point a set distance away) pre & post temporal binding adaptation (TBW & PSS training).

Change in rapid measure of gait

This measure is scored before and after PSS and TBW adaptation in UVD (unilateral vestibular dysfunction) patients. Gait is scored by performance on a task derived from the FGA (walking 40 feet while turning the head from side to side). It is scored on a 0 to 10 visual scale and provides a rapid assessment of vestibular function pre and post adaptation.

Change in measure of inducible dizziness

Looking at the change between before and after PSS and TBW adaptation in UVD (unilateral vestibular dysfunction) patients. Inducible dizziness is the symptom severity provoked by a task derived from the FGA (walking 40 feet while turning the head from side to side). It is scored on a 0 to 10 visual scale and provides a rapid assessment of vestibular function pre and post adaptation.

Change in Motion Sickness (MS) Susceptibility

The investigators will use a well-validated variant of the classic Coriolis task, a pseudo-Coriolis task where subjects view a strong yaw-axis OKN stimulus while the head is tilted passively in roll at 1.0 Hz (starting 5 s after the vection illusion begins). The investigators found empirically that 40 roll tilts of the head were adequate to induce a range of MS symptoms, from virtually none in people with minimal MS sensitivity to severe nausea in people with more prominent MS sensitivity. Subjects grade their MS symptoms before and after the pseudo-Coriolis task using a simple visual analog (0 to 10) scale.

Change in Point of Subjective Simultaneity (PSS)

Pre and post chronic motion-modulated stimulation in CI/VI patients - the PSS will be measured during temporal binding testing

Secondary Outcome Measures

Full Information

NCT ID

NCT04196933

First Posted

December 6, 2019

Last Updated

March 14, 2023

Sponsor

Massachusetts Eye and Ear Infirmary

Collaborators

National Institute on Deafness and Other Communication Disorders (NIDCD), Oregon Health and Science University, University of Geneva, Switzerland

1. Study Identification

Unique Protocol Identification Number

NCT04196933

Brief Title

Analysis of Vestibular Compensation Following Clinical Intervention for Vestibular Schwannoma

Official Title

Temporal Synthesis of Vestibular and Extra-Vestibular Sensory Signals

Study Type

Interventional

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Enrolling by invitation

Study Start Date

September 5, 2019 (Actual)

Primary Completion Date

December 31, 2023 (Anticipated)

Study Completion Date

December 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Massachusetts Eye and Ear Infirmary

Collaborators

National Institute on Deafness and Other Communication Disorders (NIDCD), Oregon Health and Science University, University of Geneva, Switzerland

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Multiple sensory cues are typically generated by discrete events, and while they do not reach the cerebrum simultaneously, the brain can bind them temporally if they are interpreted as corresponding to a single event. The temporal binding of vestibular and non-vestibular sensory cues is poorly understood and has not been studied in detail, despite the fact that the vestibular system operates in an inherently multimodal environment. In this study, the researchers are investigating the physiology and pathophysiology of vestibular temporal binding by studying normal subjects, patients with peripheral and central vestibular dysfunction, and patients with vestibular and cochlear signals provided by prosthetic implants in the inner ear.

Detailed Description

Multiple sensory cues are generated by discrete events (e.g., the vestibular-visual signals after hitting a pothole) and while they do not reach the cerebrum simultaneously, the brain can synthesize them if they are interpreted as corresponding to a single event. This is critical because the central representation of an event is improved if two or more relevant cues are integrated but conversely is degraded if unrelated inputs are synthesized. Little research has focused on temporal binding of vestibular signals with other sensory cues, even though the vestibular system operates in an inherently multimodal environment, and virtually nothing is known about temporal binding abnormalities in patients with peripheral or central vestibular disorders. The investigators will use psychophysical tests (quantifying the PSS [point of subjective simultaneity] and TBW [temporal binding window]) to study vestibular temporal binding in normal people, patients with combined vestibular and cochlear prostheses, and patients with peripheral or central vestibular dysfunction. The researchers will investigate two fundamental aspects of temporal binding: its dependence on signal precision and adaptation driven by habitual exposure to sensory patterns. Furthermore, the researchers will investigate how and why temporal binding differs from normal in patients with peripheral and central vestibular dysfunction.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Migraine, Vestibular Migraine, Vestibular Schwannoma, Motion Sickness, Dizziness, Vestibular Disorder

Keywords

sensory integration, cochlear implant, vestibular implant, balance, dizziness, vestibular disorders

7. Study Design

Primary Purpose

Basic Science

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

Participant

Allocation

Non-Randomized

Enrollment

472 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Normal Controls

Arm Type

Experimental

Arm Description

Arm Title

Central Vestibular Dysfunction

Arm Type

Experimental

Arm Description

Arm Title

Peripheral Vestibular Dysfunction

Arm Type

Experimental

Arm Description

Arm Title

Implant Subjects

Arm Type

Experimental

Arm Description

Intervention Type

Behavioral

Intervention Name(s)

Temporal Binding Adaptation - TBW training

Intervention Description

The investigators will use a temporal order judgment (TOJ) with a visual (light) cue and a motion (yaw rotation, y-translation) cue. The relative timing of the motion onset and the light are varied and subjects indicate which occurred first by pressing a button after the motion ends. The TOJ task will generate a psychometric curve and the PSS (point of subjective simultaneity) and TBW (temporal binding window) are calculated. Then training focuses on SOAs (stimulus onset asynchronies) near the TBW borders (e.g., PSS +/- 0.5xTBW), starting from 50 ms outside the TBW and moving randomly towards the PSS. The goal of the training is to narrow the TBW -- training trials will be provided for 30 min and after each response the subject is told if their response was right or wrong. After training, the TOJ task is repeated to determine how the TBW has changed. Sham training will be the same as the actual training except that verbal feedback of response accuracy will not be provided.

Intervention Type

Behavioral

Intervention Name(s)

Temporal Binding Adaptation - PSS training

Intervention Description

After the PSS and TBW are calculated with the standard TOJ paradigm, 100 training trials are provided where the SOA is set to [PSS - 200 ms], with the goal of shifting the PSS more negative. Then the TOJ task will be repeated but every 10 testing trials will be followed by 10 training trials (SOA = PSS - 200), and this pattern will be repeated 10 times to 100 more training trials interspersed with the Post TOJ data. Subjects will respond after all trials and testing and training will not be distinguished. After this is completed, the new PSS and TBW are calculated. Sham PSS training will be identical to the above except that the 'training' period will consist of random SOAs rather than a series of fixed SOAs.

Intervention Type

Behavioral

Intervention Name(s)

Temporal Binding Adaptation - PSS adaptation with VI stimulation

Intervention Description

The adaptation will utilize the same approach used in non-implanted patients. The investigators will provide a repeated, fixed SOA with either the CI or VI leading the other stimulus by 220 ms. After the training period, which will match the number of stimuli pairs provided to our normal vestibular-auditory control subjects undergoing PSS adaptation, the TOJ study is repeated to recalculate the PSS and TBW.

Intervention Type

Behavioral

Intervention Name(s)

Chronic Motion-modulated Stimulation

Intervention Description

To provide 8 hours of 'physiologic' CI and VI inputs during normal activities, the investigators will employ standard motion-modulated stimulation with the VI. This requires pre-adaptation to a 200 pps tonic stimulation rate (to emulate the push-pull design of the native vestibular system allowing modulating stimulation upward or downward with opposite directions of motion). The three electrodes are connected to the head-mounted prosthetic circuit, which consists of three angular velocity sensors (one aligned with the sensitive axis of each canal) such that head rotations in the plane of the given canal modulate the stimulation rate of the corresponding electrode, upward (for ipsi) or downward (for contralateral) head rotations, thereby simulating normal canal-mediated modulations.

Primary Outcome Measure Information:

Title

Changes in postural sway/balance

Description

Time Frame

baseline and post temporal binding adaptation (1 hour)

Title

Change in rapid measure of gait

Description

Time Frame

baseline and post temporal binding adaptation (1 hour)

Title

Change in measure of inducible dizziness

Description

Time Frame

baseline and post temporal binding adaptation (1 hour)

Title

Change in Motion Sickness (MS) Susceptibility

Description

Time Frame

baseline and post temporal binding adaptation (1 hour)

Title

Change in Point of Subjective Simultaneity (PSS)

Description

Pre and post chronic motion-modulated stimulation in CI/VI patients - the PSS will be measured during temporal binding testing

Time Frame

baseline and 1 hour post 8-hour VI-CI 'physiologic' stimulation

10. Eligibility

Sex

All

Minimum Age & Unit of Time

8 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Normal subjects normal vestibular-oculomotor exams normal low-frequency standard rotational testing normal hearing Migraine meets International Headache Society (IHS) criteria for migraine with or without aura tested more than 2 weeks after most recent migraine headache Vestibular Migraine meets Barany Society criteria for vestibular migraine, which includes: episodic vestibular symptoms that occur with headaches that meet the IHS criteria for migraine tested more than 2 weeks after most recent migraine headache or vestibular episode Vestibular Schwannoma existence of unilateral vestibular schwannoma (pre & post clinical intervention e.g. surgical resection) must plan to have clinical intervention such as sub-occipital surgical approach with complete sectioning of the vestibular nerve rotational testing to assess pre-surgical vestibular function audiogram brain MRI consistent with vestibular schwannoma audiography in each ear Vestibular (VI) and Cochlear (CI) Implant subjects scheduled for CI surgery because of deafness minimum 5 year history of documented absence of auditory and vestibular function, based on review of their audiograms and vestibular tests specific vestibular criteria: peak ice water caloric response of less than 3deg/s for each ear; yaw VOR time constant <3s and gain <0.25; and reduced head impulse gain (<0.25) for all canal planes specific audiographic criteria: 80dB or greater sensorineural hearing loss in both ears Exclusion Criteria: Normal subjects history of otologic or neurologic disease on vestibular suppressant medication (benzodiazepine, antihistamine, anticholinergic) pregnant or recently (<6mos) pregnant Migraine history of vestibular symptoms (other than motion sickness) evidence of other neurologic or otologic dysfunction on migraine prophylactic medications on vestibular suppressant medication (benzodiazepine, antihistamine, anticholinergic) Vestibular Migraine (VM) other neurologic or otologic dysfunction as defined above except for central eye movement findings that are consistent with VM and therefore not exclusionary. on migraine prophylactic medication on vestibular suppressant medication (benzodiazepine, antihistamine, anticholinergic) Vestibular Schwannoma other otologic disease (other than presbycusis) or any neurologic disease (other than migraine) on vestibular suppressant medication (benzodiazepine, antihistamine, anticholinergic)

Facility Information:

Facility Name

Massachusetts Eye and Ear Infirmary

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02114

Country

United States

12. IPD Sharing Statement

Learn more about this trial

Analysis of Vestibular Compensation Following Clinical Intervention for Vestibular Schwannoma

We'll reach out to this number within 24 hrs