Analysis of Vestibular Compensation Following Clinical Intervention for Vestibular Schwannoma

Not Applicable

• Conditions: Vestibular Schwannoma; Vestibular Disorder; Dizziness; Migraine; Vestibular Migraine; Motion Sickness
• Interventions: Behavioral: Temporal Binding Adaptation - TBW training; Behavioral: Temporal Binding Adaptation - PSS adaptation with VI stimulation; Behavioral: Temporal Binding Adaptation - PSS training; Behavioral: Chronic Motion-modulated Stimulation

• Registration Number: NCT04196933
• Lead Sponsor: Massachusetts Eye and Ear Infirmary

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.

Study Timeline

• Study Start: 2019-09-05
• Study First Submitted: 2019-12-06
• Study First Submitted QC: 2019-12-10
• Study First Posted: 2019-12-12
• Status Verified: 2023-03
• Last Update Submitted: 2023-03-14
• Last Update Posted: 2023-03-16
• Primary Completion: 2023-12-31
• Study Completion: 2023-12-31

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: All
• Target Recruitment: 472

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

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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)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Normal Controls	Temporal Binding Adaptation - PSS training	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).
Central Vestibular Dysfunction	Temporal Binding Adaptation - PSS training	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).
Peripheral Vestibular Dysfunction	Temporal Binding Adaptation - PSS 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).
Normal Controls	Temporal Binding Adaptation - TBW training	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).
Central Vestibular Dysfunction	Temporal Binding Adaptation - TBW training	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).
Peripheral Vestibular Dysfunction	Temporal Binding Adaptation - TBW 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).
Implant Subjects	Temporal Binding Adaptation - PSS adaptation with VI stimulation	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.
Implant Subjects	Chronic Motion-modulated Stimulation	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.

Primary Outcome Measures

Name	Time	Method
Change in Point of Subjective Simultaneity (PSS)	baseline and 1 hour post 8-hour VI-CI 'physiologic' stimulation	Pre and post chronic motion-modulated stimulation in CI/VI patients - the PSS will be measured during temporal binding testing
Change in measure of inducible dizziness	baseline and post temporal binding adaptation (1 hour)	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.
Changes in postural sway/balance	baseline and post temporal binding adaptation (1 hour)	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	baseline and post temporal binding adaptation (1 hour)	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 Motion Sickness (MS) Susceptibility	baseline and post temporal binding adaptation (1 hour)	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.

Trial Locations

Locations (1)

Massachusetts Eye and Ear Infirmary; 🇺🇸 Boston, Massachusetts, United States