As for earlier human studies (e.g., Benson et al., 1986
), we utilized a direction recognition task in which subjects report the direction of motion. Most general methods mimic those we've published (e.g., Grabherr et al., 2008
). The study was approved by the local ethics committee and was performed in accordance with the ethical standards of the 1964 Declaration of Helsinki. All subjects filled out a general health questionnaire. Normal subjects were also pre-screened via clinical diagnostic testing to confirm the absence of undiagnosed vestibular disorders. Screening consisted of caloric, electronystagmography, Hallpike testing, angular VOR evoked via rotation, and posturography. 14 healthy normal volunteers (9 females - 5 males) participated. The mean age was 36 (σ = 10).
To ensure that the vestibular-deficient patients had no residual vestibular function, we studied three patients who had undergone bilateral surgical ablation of both inner ears for bilateral vestibular schwannomas associated with neurofibromatosis type 2 (NF-2). We only included patients whose nerve sections were accomplished via a translabyrinthine nerve section or a transcochlear nerve section with a labyrinthectomy, because these are the only methods that ensure complete vestibular deafferentation. All three patients were deaf and utilized an auditory brainstem implant during testing.
Patient A was a 24-year old female who competed in triathlons and marathons. She first had right-sided labyrinthectomy at age 9, followed by left-sided labyrinthectomy at age 19. Patient B was a 26-year old male who underwent right- and left-sided labyrinthectomies at ages 5 and 20, respectively. Though he walks with a limp, he is able to ride a bicycle. Patient C was a 53-year old female with a history of two right ear vestibular schwannoma removals. The first surgery was performed at age 29 using a suboccipital approach. Due to a regrowth, she needed a second removal at age 38, this time using a translabyrinthine approach. Left-sided labyrinthectomy was performed when the patient was 47. Additional clinical information is provided in .
Patient clinical characteristics.
Standard neurological exams showed no signs of myelopathy and no substantive sensory deficits other than auditory and vestibular. Pressure sensation on the trunk and buttocks was tested in several locations in patients A and B using Semmes-Weinstein monofilaments (Tracey et al., 2012
). Although patient A had 13 spinal tumors and patient B had only several small spinal tumors, we found that their pressure thresholds on the trunk were comparable and were also comparable to those from a normal control subject. These findings suggest that the presence or absence of spinal tumors most likely did not influence peripheral sensation.
Subjects were 1) rotated in yaw, 2) translated along an earth-vertical superior-inferior axis (“z-translation”), 3) translated along an earth-horizontal inter-aural axis (“y-translation”), or 4) tilted in roll about an earth-horizontal, head-centered, naso-occipital axis. Subjects always began - and except for roll-tilt remained - upright with respect to gravity. Motion stimuli were generated using a MOOG 6DOF motion platform. Single cycles of sinusoidal acceleration were applied. The peak acceleration (A), peak velocity (vp) and total lateral displacement (Δp) are proportional to one another. (vp = A /(πf) = 2f Δp). These motion profiles were chosen because they mimic natural volitional head movements.
A brief low pitch “warning” tone was administered before the onset of each motion stimulus. At the end of each trial a brief high pitch sound indicated that the subject needed to respond. Each subject was instructed to push the button in their left hand if they perceived a leftward (downward) motion or to push the button in their right hand for rightward (upward) motion. When subjects were uncertain of the motion direction, they were instructed to make their best guess.
Subjects were seated in a chair with a 5-point harness in an upright position. The subject's head was held in an adjustable helmet that was carefully centered relative to the axes of rotation within about 1 cm (Grabherr et al., 2008
). To eliminate the influence of visual cues, trials were performed in the dark in a light-tight room. To minimize the influence of other sensory systems, all skin surfaces except the face were covered (long sleeves, light gloves); a clear visor was attached to the helmet surrounding the face. For normal hearing subjects, noise cancelling earplugs reduced external noise by more than 20 dB, and remaining auditory motion cues were masked by white noise (circa 60 dB). Tactile cues were distributed as evenly as possible using padding.
Each frequency was tested in a block of trials before switching to another frequency. All four conditions were tested at 0.5, 1, 2, and 5Hz. For yaw rotation, results are also reported for 0.2Hz. For y-translations and z-translations, results are also reported for 0.3Hz. For roll-tilts, results are also reported for 0.05, 0.1, and 0.2Hz. Because of device displacement limitations, not all subjects were able to complete testing at all frequencies. As will be shown, patients could only complete testing at the highest frequencies for some motion conditions. For normal subjects, who typically completed testing at all frequencies, testing took 10 to 12 hours. For total loss patients, who often could not complete tests at lower frequencies, testing took 6 to 8 hours. Testing for both normals and patients was typically broken up into multiple test sessions of 30 to 90 minutes each.
Like earlier studies (Hall, 1981
), we use a hybrid approach to estimate the parameters of the psychometric function. We combine an adaptive 3-down/1-up staircase (e.g., Leek, 2001
), which sets the stimulus magnitude for each trial, with a maximum likelihood fit of the data. Direction of motion (e.g., left or right) was randomized. The maximum likelihood fit was performed using a generalized linear model (GLM) (e.g., McCullagh and Nelder, 1990
; Dobson and Barnett, 2008
; Zupan and Merfeld, 2008
). Specifically, a Gaussian cumulative distribution function was fit to the data using a generalized linear model (GLM) with a probit link function, yielding a “maximum likelihood” model fit. The data included a peak angular velocity amplitude vector (ω) and a binary motion direction response vector (y
). The function call in MATLAB was b=glmfit(ω,y,`binomial',`link',`probit') using the statistics toolbox (v 7.0), where b is a 2-element vector. The elements of b are related to an underlying Gaussian probability distribution (e.g., Dobson and Barnett, 2008
), having a “vestibular bias” (μ), which represents an offset from zero (Merfeld, 2011
), μ = −b
(2), and a “one-sigma threshold” (σ), which represents the standard deviation of the noise, σ = 1/b
After each trial, the GLM fit was performed. Data collection for each subject was terminated when the coefficient of variation (CV) for the b(2) fit parameter – the one representative of the one-sigma threshold for that test condition - was less than 0.2; this means that the estimated standard deviation of the spread parameter was less than 20% the magnitude of the estimated spread parameter. On average, 70 to 80 trials were required to yield the desired CV. Sometimes testing had to be terminated before this criterion was met. This occurred when the 3D/1U staircase algorithm required large motion stimuli that exceeded the capabilities of our motion device. Prematurely terminated test sessions were repeated if time allowed. Data from two or more such test sessions were combined for analysis. Due to the probabilistic nature of thresholds, it is impossible to translate device limitations to precise measureable threshold limits, but limits would be about 30°/s for rotation or tilt and 30 cm/s for translation.
As for earlier studies (Benson et al., 1986
; Benson et al., 1989
; Grabherr et al., 2008
), the geometric mean across subjects was calculated because the data demonstrated a lognormal distribution across subjects. Statistical analyses were performed using a Wilcoxon rank sum test for each of the four conditions.